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PMC-Treatment

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PMC11826323_7	RP treatment aims to control inflammation, preserve organ function, and prevent irreversible damage. Glucocorticoids remain the mainstay for acute flares; immunosuppressants (cyclosporine, methotrexate, cyclophosphamide) or biologic agents (TNF inhibitors, tocilizumab, IL‐1 inhibitors, IL‐6 receptor antagonist) may be necessary for organ‐threatening or refractory disease [21, 22]. Evidence from recent observational cohorts suggested that early use of biologic therapies could improve respiratory outcomes, particularly in patients with severe airway involvement. In cases of significant airway compromise, local interventions (e.g., bronchoscopic stenting and balloon dilation) may be required.
PMC11631605_4	Biologics have been reported as a treatment option for patients with anti-MDA5-positive JDM complicated by RP-ILD. Rituximab is conditionally recommended as one of the first-line treatment options for RP-ILD. There are also case reports/series of other biologics, such as infliximab, basiliximab, and daratumumab, but the number of cases is minimal, and larger prospective controlled studies are needed. Although the 2023 ACR guideline conditionally recommends against tocilizumab as a first-line treatment for RP-ILD in patients with systemic autoimmune rheumatic diseases, recent studies have shown that the levels of inflammatory cytokines, such as type 1 interferon, interleukin (IL)-6, and IL-18, are significantly increased in patients with anti-MDA5-positive DM-ILD. IL-6, in particular, is closely related to the pathogenesis of this condition. A hyperinflammatory state is a distinctive feature of anti-MDA5-positive DM with RP-ILD. The serum IL-6 level in the RP-ILD subgroup of polymyositis (PM)/DM patients is higher than that in the non-ILD subgroup, suggesting that regulating this cytokine might offer a possible treatment strategy for RP-ILD.
PMC11473280_4	Compared with anti-MDA5 Ab-negative DM patients, pre-treatment serum levels of interleukin (IL)-6, IL-10, IL-18, macrophage colony-stimulating factor, interferon (IFN)-α, and ferritin were significantly elevated in anti-MDA5 Ab-positive DM patients, suggesting that the activation of monocytes and macrophages underlies the pathophysiology of anti-MDA5 Ab-positive DM (8). Gono et al. reported that serum ferritin and IL-18 levels were significantly reduced in patients with anti-MDA5 Ab-positive DM and ILD who responded to treatment (18). In addition, the anti-MDA5 Ab titer is reported to be directly related to the disease activity and prognosis in anti-MDA5 Ab-positive DM with RP-ILD (4). PE, which can reduce anti-MDA5 Ab titers and levels of various cytokines, may thus be effective against anti-MDA5 Ab-positive DM with RP-ILD. Several recent reports have described the efficacy of PE in patients with anti-MDA5 Ab-positive DM and RP-ILD who have proven refractory to combined immunosuppressive therapy. Abe et al. showed that, in 10 patients with anti-MDA5 Ab-positive DM with PR-ILD who were refractory to triple therapy, the 1-year survival rate of the 6 patients treated with PE was significantly higher (100%) than that of the 4 patients without PE (25%) (19). Similarly, Shirakashi et al. showed that, of 13 patients with anti-MDA5 Ab-positive DM with ILD who were refractory to triple therapy, the 3-year survival rate of the 8 patients treated with PE (62.5%) was significantly higher than that of the 5 patients without PE (0%) (20). Saito et al. reported that, in 6 patients with anti-MDA5 Ab-positive CADM with RP-ILD who were refractory to triple therapy and underwent PE (median time from diagnosis to start of PE, 11.5 days), the 2 who died had higher AaDO2 levels, more severe lung lesions at initiation of PE, and a longer period before initiation of PE than the 4 who survived, suggesting that the early initiation of PE may improve the prognosis by preventing ILD progression (21).
PMC11631605_7	Anti-IL-6 therapy emerges as a novel approach for the treatment of refractory anti-MDA5-positive JDM with RP-ILD, particularly in cases where conventional treatments prove inadequate.
PMC11473280_8	TOF is a Janus kinase (JAK) inhibitor that mainly inhibits JAK1 and JAK3 and suppresses the signaling of various cytokines, such as type I IFNs (IFN-α/β), IL-6, IL-7, IL-10, IL-15, and IL-21, by inhibiting the JAK-signal transducer and activator of the transcription signaling pathway (30). Several reports have demonstrated the efficacy of TOF in patients with anti-MDA5 Ab-positive DM and ILD. However, patients treated with combined immunosuppressive therapy and TOF reportedly experience complicated adverse events, particularly viral infections.
PMC11509757_4	Intriguingly, fingolimod was also explored as a potential treatment strategy for people with moderate to severe COVID-19, and a protective effect against SARS-CoV-2-induced hyper-inflammation was suggested for this DMT class, based on both S1P receptor-dependent and -independent mechanisms. Furthermore, available evidence suggests that the use of ponesimod and other newer-generation i-mods is associated with higher seroconversion rates compared to fingolimod, possibly offering a more effective infection control and anti-viral response to SARS-CoV-2 and other pathogens.
PMC11660005_1	The incidence of adult duodenal trauma is 0.2% to 0.6% in all trauma patients and 1% to 4.7% in all abdominal trauma patients [9]. Penetrating trauma is the most common cause of duodenal injury in adult patients, and the duodenum injury scale is classified using the AAST grading scale as grade I to V [9]. Although many approaches have been proposed to cure duodenal trauma, the risk of complications remains high. Especially in complex duodenal injury, the incidence of complications is as high as 65%, and overall mortality ranges from 5% to 30% [10]. Principles of surgical treatment of duodenal trauma include damage control techniques, resection of non-viable tissue, restoring continuity of the gastrointestinal tract, diverting gastrointestinal contents, restoring bile and pancreatic enzymes, creating conditions for healing, and providing enteral nutrition access [9–12]. Pancreaticoduodenectomy is the only possible treatment indicated for the most complex injuries (grades IV and V) [13].
PMC11414482_1	While the observed 24 hours systolic ambulatory BD reduction at 6-months follow-up in contemporary trials such as SPYRAL ON MED is generally considered to be modest (−1.9 mmHg),6 it seems that the observed treatment effect in our patient was much more pronounced. Previous studies showed that the density of orthosympathetic nerves increases progressively with increasing distance from the ostium. Additionally, in a percutaneous approach the nerves that are located at the outer border of the vessel may be incompletely targeted. Therefore, it seems plausible that a surgical approach would result in more profound and more complete orthosympathetic denervation.5
PMC11602498_1	Abrocitinib, a selective JAK1 inhibitor, affects epidermal barrier modulation and peripheral nerve modulation involved in pruritus transduction by targeting the JAK- signal transducer and activator of transcription (STAT) signaling pathway (12). Although the pathogenesis of LA is unclear, IL-31, one of the cytokines involved in the JAK-STAT signaling pathway, is considered to be a central mediator of T-cell–mediated pruritus. Furthermore, several articles have indicated that pruritus in LA may be correlated with the hypersensitivity of dermal nerve fibers, which are linked to IL-31 receptors in the epidermis (13). JAK1 inhibitors are known to directly affect T-cell function; moreover and importantly, blockade of IL-31 and IL-4 signaling by these inhibitors in primary afferent sensory neurons can influence inflammation and neurosensory pathways (14, 15).
PMC11455802_1	Selective JAK1 inhibitors, such as upadacitinib and abrocitinib, have demonstrated in clinical trials and practice the ability to rapidly and efficiently reduce itching, making them effective for treating conditions such as atopic dermatitis characterized by severe pruritus [9]. One probable explanation is that JAK1 can efficiently inhibit inflammatory factors that produce pruritus, such as IL-31 and INF-γ [10]. JAKi can reduce GC doses from 64% to 80% in AOSD patients, although not all achieve remission [1, 6].
PMC11513297_0	Janus kinases (JAKs) are a class of intracellular non-receptor tyrosine kinases composed of JAK1, JAK2, JAK3, and TYK2 subtypes. It is associated with signaling downstream of various type I and type II cytokines (such as IL-6, IL-17, IL-19, IL-20, IL-22, IL-23, IFN-γ, etc.) receptors. These cytokines and signaling pathways are involved in biological processes such as immune cell differentiation, maturation, humoral immune regulation, immune barrier function, cell proliferation, and apoptosis, and play a key role in autoimmune, allergic, and inflammatory disease responses (11). Abrocitinib is a selective inhibitor of JAK1 that reversibly and selectively inhibits JAK1 by blocking the adenosine triphosphate binding site. On April 8, 2022, Abrocitinib was approved by the China National Medical Products Administration. For the treatment of adults with moderate-to-severe atopic dermatitis who do not respond well to other systemic therapies (such as hormones or biologics) or who are not appropriate for existing therapies.
PMC11249543_5	The pathogenesis of inflammatory skin diseases is intricately regulated by the dynamic interplay between cytokines, immune cells, and tissue cells. The JAK-STAT signaling pathway assumes a crucial role in this intricate network. The JAK family, comprising JAK1, JAK2, JAK3, and tyrosine kinase(TYK) 2, activates STATs through autophosphorylation. A multitude of cytokines heavily rely on the JAK-STAT pathway for their signaling, including IFN-α/β, IFN-γ, interleukins (IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21) that share the IL-2 receptor common γ chain, IL-5, IL-6, IL-12, IL-13, and IL-23. Notably, while TNF-α, IL-1, and IL-17 do not directly engage the JAK-STAT pathway, the use of JAK inhibitors can indirectly impede upstream STAT-dependent cytokines (e.g., IL-23), thereby attenuating downstream cytokines (e.g., IL-17) (7).
PMC11624682_4	Abrocitinib is a JAK1 inhibitor approved by the FDA for the treatment of AD, which reduces the activity of various Th2 cytokines (such as IL-4 and IL-13) in AD by inhibiting JAK/STAT-1 signaling. Additionally, abrocitinib attenuates inflammation, and reducing damage to immune cells at the skin barrier. The most frequently reported side effects are gastrointestinal symptoms, acne and respiratory tract infections. Moreover, JAK inhibitors disrupt the intracellular signalling pathways responsible for the activation of immune cells and production of pro-inflammatory cytokines that are involved in the development of vitiligo. Only topical ruxolitinib has been approved for the treatment of vitiligo in patients aged ≥12 years; indications for other JAK inhibitors such as tofacitinib and baricitinib in the treatment of vitiligo are lacking.
PMC11532939_0	The establishment of standardized therapeutic guidelines for the treatment of cervical cancer during pregnancy is still pending, resulting in using multiple therapeutic regimens. Severe fetal anemia can lead to hydrops fetalis and, ultimately, fetal demise. The presence of fetal anemia could potentially be associated with the administration of ifosfamide, a drug recognized for its notable myelotoxicity. The administration of cisplatin is linked to the risk of platinum-induced hearing loss in the fetus as the most severe side effect. The risk of ototoxicity increases with a higher total cumulative dose of cisplatin. In vitro studies have shown a relatively low transplacental transfer of cisplatin, a phenomenon that escalates with the progression of gestational age. Paclitaxel is a chemotherapeutic agent with minimal side effects and a low fetal plasma concentration. Carboplatin is known for its risk of fetal hematotoxicity, but has a lower risk of platinum-induced hearing loss.
PMC11541060_1	For pregnant women, in general, with cervical cancer who desired to continue the pregnancy, NACT beyond the first trimester was recommended to enable fetal maturation to avoid risk of spontaneous abortion, fetal death, and fetal defects [12]. Previous study on 21 patients with cervical cancer in pregnancy treated with three cycles of neoadjuvant platinum‐based chemotherapy demonstrated that platinum concentrations in the amniotic fluid were demonstrably lower than in the umbilical cord blood (11%–42% vs. 23%–65%), suggesting a placental filtration mechanism for platinum [13]. Prenatal exposure to maternal cancer with or without treatment did not impair the cognitive, cardiac, or general development of children in early childhood [14].
PMC11841137_1	Traditional anesthetics and analgesics frequently utilized in general anesthesia possess potent cardiodepressive properties, potentially leading to significant hemodynamic fluctuations. Additionally, tracheal intubation inherently elicits airway irritation, exacerbating pre-existing pulmonary conditions and complicating extubation maneuvers. Moreover, intrathecal anesthesia was contraindicated due to his coagulation disorder. Nerve block anesthesia offers a viable alternative, circumventing such risks adeptly. Nerve block facilitates profound and prolonged anesthesia with minimal doses of local anesthetics, ensuring preserved spontaneous respiration. Furthermore, its analgesic efficacy may endure for up to 8–10 h postoperatively [2], markedly reducing reliance on opioid analgesia and its associated adverse effects. A retrospective study has highlighted that regional anesthesia was associated with a modestly shorter length-of-stay compared with general anesthesia [10]. Employing ultrasound-guided technology in nerve blockade substantially mitigates the potential for tissue trauma and local anesthetic mistakenly entering blood vessels, thus enhancing procedural reliability and safety [2]. Previously, nerve block was used more intraoperatively combined with general anesthesia, aimed at dose reduction of opioid medications [3, 7] or postoperative analgesia [3, 11, 12]. However, emerging literature suggests the feasibility of employing simple nerve blocks for selected procedures [7, 13].
PMC11546046_2	Biologically, the three fundamental principles for bone formation are addressed in the management of femoral neck non-union. Autogenous bone marrow provides osteogenic properties and centrifugation concentrates necessary elements, increasing efficiency. Corticocancellous bone allograft offers osteoconductivity and mechanical support for cells differentiating into osteogenic cells, while DBM provides osteoinductive activity, enabled by bone morphogenetic proteins present in the DBM.
PMC11531864_0	Surgically-induced necrotizing scleritis is a rare yet serious complication following ocular surgery, which can occur anywhere from the first postoperative day to several years later. This condition presents diagnostic challenges, as scleral thinning may be overlooked. In advanced cases, significant visual impairment, scleral necrosis, anterior staphylomas, and peripheral corneal ulcers may develop. To rule out infectious causes, it is crucial to perform a scleral biopsy and intraocular samples for PCR analysis and wound scraping for microbiological culture. Given the potential impact on vision, early intervention is vital. Diabetes mellitus may exacerbate this condition by creating a pro-ischemic inflammatory environment.
PMC11531864_1	Oral prednisolone is often considered the first-line treatment for non-infectious necrotizing scleritis, while intravenous methylprednisolone may be used in severe cases. Additional therapies may include non-steroidal immunotherapy, monoclonal antibodies against tumor necrosis factor-alpha, interleukin-6 inhibitors, and anti-CD20 targeted drugs. For cases with progressive scleral necrosis, surgical options such as conjunctival debridement, conjunctival and Tenon's flap grafts, amniotic membrane transplantation, and scleral patch grafts may be necessary.
PMC11367887_5	Therapeutic regime for SJS/TEN includes discontinuation of allergenic drugs, glucocorticoids, nutrition support, insulin, and intravenous immunoglobulin (IVIG) [24]. Extensive epidermolysis and necrosis lead to thermoregulation disorder, fluid loss, and blood volume shortage. Skin infection induced sepsis is the major cause of death [25]. Thus, rehydration and antibiotics are dominant forces in improving outcomes. Corticosteroids, IVIG, cyclosporine, TNF-α inhibitors, and plasma exchange have some beneficial effects on mitigating skin lesions [26], while the evidence for lowering mortality remains controversial. It should be noted that long-term and high-dose glucocorticoids may increase the risk of sepsis and have a detrimental impact on blood glucose control in FT1DM. Therefore, for those who cannot tolerate glucocorticoids, intravenous immunoglobulin (IVIG) or immunosuppressive agents are an alternative.
PMC11818212_4	These findings suggest that a treatment strategy that aim to “aggressively” mediate the inflammatory response (even when it is exacerbated) may yield more favorable outcomes than those that do not in cases of significant body surface area damage. The levels of TNF-α, granzyme B, and perforin during the acute phase of the reaction in SJS/NET were higher than normal, while these levels returned to normal after the reaction had resolved. The fundamental elements of the therapeutic regimen of this kind of patients are wound care and supportive care. The literature indicates that the use of intravenous immunoglobulins and steroids, cyclosporine, plasmapheresis, and TNF-α inhibitors has been associated with a reduction in mortality and morbidity in pediatric patients. In a study conducted in Ankara, the dermatological manifestations associated with SARS-CoV-2 infection in pediatric patients were evaluated. Of the 5143 infected children, only 13 (0.25%) developed skin lesions, with maculopapular exanthema (61.5%) and urticaria (23%) being the most frequent. The interleukins primarily involved in TEN were IL-4, IL-6, and IL-12, which were modulated (downregulated) by TEN, along with augmented IL-1α, IL-1β, IL-5, IL-8, NF-κβ, and interferons (IFN; α, β, and γ), which were modulated by COVID-19.
PMC11578727_5	Although KLHL11 encephalitis is mediated through T cell immunity, the favorable tried treatment of CD20 monoclonal antibodies in KLHL11 encephalitis may suggest that inducing B cell depletion is an effective and safe option. This mechanism may involve B cell depletion reduces the production of KLHL11 antibodies and inhibits the antibody-associated paraneoplastic neurological syndrome. In addition, B cell depletion inhibits autoreactive T cell responses to restrict the inflammatory cascade and accelerate recovery in KLHL11 encephalitis.
PMC11578727_3	Neuropathological studies revealed that the brain of KLHL11 encephalitis patient exhibited chronic lymphocytic inflammation, mainly T cell infiltration, accompanied by non-necrotizing granulomas (3). This study demonstrates that cytotoxic T cell-mediated immune effects play a crucial role in the pathogenesis of KLHL11 encephalitis (13). Studies suggest that patients with KLHL11 encephalitis have a more difficult-to-treat course than patients with other antibodies against neuronal cell surface antigens (15). Clinicians often use corticosteroids, intravenous immune globulin, or plasma exchange as first-line treatments. Ofatumumab is a CD20 monoclonal antibody that selectively induces B cell depletion.
PMC11578727_4	Ofatumumab displays specific CD20 affinity and a slow off-rate through complement-dependent cytotoxicity, leading to efficient B cell lysis. Ofatumumab was the first monoclonal anti-CD20 antibody approved for use against human disease and recognizes a different epitope that is distinct from rituximab (16). Ofatumumab was approved for the treatment of relapsing forms of multiple sclerosis in 2020 (17). It can be done by yourself by subcutaneous injection. Ofatumumab is a fully human antibody with unique advantages. It is less immunogenic than rituximab and has a good safety profile (17). The current regimen of ofatumumab for the treatment of multiple sclerosis is 20 mg subcutaneously on days 1, 7, 14, and 28, followed by 20 mg subcutaneously every 4 weeks (18).
PMC11632487_4	Treatment of ABC with intraosseous doxycycline injection was first introduced in 2012, with the aim of restoring normal anatomy and function while reducing local recurrence and minimizing morbidities. Primarily used as an antibiotic, doxycycline has also been shown to have antitumoral properties by inhibiting matrix metalloproteinases and angiogenesis in some bone and soft-tissue malignancies, inducing osteoclastic apoptosis and causing a reaction leading to fibrin and collagen deposition. Its use as an osteotactic agent with albumin as the drug vehicle has also been reported. Previous studies have shown that doxycycline administration is an effective alternative in the treatment of ABCs in non-expendable areas. Literature describes ABC as healed if no recurrence is seen within 2 years after completing treatment.
PMC11658006_2	Doxycycline, in addition to being a caustic sclerosant, is an antibiotic that inhibits matrix metalloproteinases, enzymes responsible for ABC-induced bone destruction. Also, experimental studies in rodents with periodontitis demonstrated antiresorptive and anti-inflammatory properties of doxycycline, suggesting its potential use encouraging maxillofacial bone repair in humans. In clinical practice, percutaneous doxycycline sclerotherapy has shown promise as an ABC treatment.
PMC11843777_8	Recent studies have explored the use of doxycycline injections for the treatment of ABCs due to their sclerosing effects [13,20,21]. Doxycycline inhibits matrix metalloproteinases (MMPs), which are involved in the degradation of bone and extracellular matrix, although its precise effects on MMPs remains a topic of debate. Additionally, it inhibits vascular endothelial growth factor (VEGF), which promotes angiogenesis crucial for growth and maintenance of ABCs [22]. Although doxycycline use is cautioned in children younger than 8 years old because of its potential to cause enamel pigmentation, the safety profile of doxycycline injections for SBCs has shown promise [23]. To date, only 1 study has evaluated the use of doxycycline in SBCs; Wong et al [24] treated 77 patients, aged 3–34 years, with ABCs (n=50) and SBCs (n=27) with doxycycline sclerotherapy. Only 1 lesion failed sclerotherapy and required surgical excision. The authors observed high levels of patient satisfaction, with little to no pain, almost no functional impairment, and low rates of adverse events.
PMC11606025_8	Surgical challenges in treating mirror hand arise from neurovascular anatomical variations, such as duplication of the ulnar artery, shortening of the radial nerve, absence of the radial artery, and abnormal arterial arches. Preoperative three-dimensional (3D) printing has been suggested to better understand the complex anatomy before surgery. The goals of surgical management in mirror hand include pollicization of the best-suited digit (better functional digit on the preaxial border) along with selective amputation of supernumerary digits. The extra redundant skin and intrinsic musculature of amputated digits are used for reconstruction of the first web space and thenar eminence to create a functional thumb. The extensor tendons of ablated digits can be used to augment the wrist extensors if there is a preoperative flexion deformity of the wrist.
PMC11606025_6	Early pollicization tends to yield better outcomes. Thumb reconstruction in mirror hand is a technically demanding procedure that requires proper preoperative planning owing to the wide variation in anatomy and complexity. Nevertheless, successful outcomes have been reported in neglected cases of mirror hand managed with pollicization and excision of extra digits in adolescent patients [3, 14].
PMC11646647_7	Severe gingival overgrowth associated with generalized stage 4, grade C periodontitis often requires a multi-disciplinary approach, involving complex treatments such as antibiotic therapy, biopsies, extractions, gingivectomy, gingivoplasty, and osteoplasty. To achieve optimal patient outcomes, it is essential to coordinate care among a team of oral healthcare professionals, such as periodontists, dental surgeons, prosthodontists, oral pathologists, and oral microbiologists. This collaborative approach ensures a correct diagnosis and a comprehensive, tailored treatment plan that addresses the patient's complex needs. In addition to GE, METH use can contribute to other significant oral health issues, such as xerostomia and an increased risk of dental caries. Therefore, clinicians must account for the extensive effects of METH on oral tissues when developing a treatment plan. Patient education plays a pivotal role in care, emphasizing the importance of proper oral hygiene, dietary modifications, and lifestyle changes. These comprehensive strategies are crucial not only for preventing further damage and managing current oral health issues but also for promoting long-term oral and overall well-being.
PMC11414368_3	The substantial enhancement in airflow limitation (FEV1 increase of 820 mL) observed following ESS may be attributed to the suppression of T2 inflammation. Several studies have indicated that controlling T2 inflammation in patients with severe asthma leads to improved airflow limitations. For instance, a previous study showed that 1-year treatment with mepolizumab (anti-IL-5 therapy) in 44 patients with severe eosinophilic asthma and CRSwNP yielded enhancements in %FEV1, along with a substantial reduction in blood eosinophil count and sinonasal outcome test-22 scores (13). Another study showed that dupilumab (anti-IL-4/13 therapy) significantly improved airflow limitation and reduced T2 inflammatory markers, such as FeNO and immunoglobulin E (IgE), in patients with moderate-to-severe asthma (14). A plausible explanation for the improvement in airflow limitation stemming from treatments targeting T2 cytokines is that the suppression of these mediators results in reduced mucus secretion in the airways and bronchoconstriction, which provides relief from airflow limitation (15). Thus, the substantial improvement in FEV1 observed through ESS in this case may be attributed to the suppression of T2 inflammatory pathways, which is consistent with findings from previous studies on biological agents that target T2 cytokines. Nonetheless, even CRSwNP patients with asthma who have airway remodeling might benefit from ESS through improvement of asthma symptoms and T2 airway inflammation.
PMC11628187_0	Biologics have been reported to improve mucus plugs. Serum and sputum eosinophil peroxidase levels were correlated with the mucus score and were significantly attenuated by treatment with mepolizumab. Dupilumab contributes to a greater reduction in mucus plugging with greater improvement in ventilation quantified using 129Xe magnetic resonance imaging compared with placebo. In Japan, dupilumab has also been shown to have a beneficial effect on mucus plugs evaluated on CT in patients with asthma. Increasing dose of ICS might be also considered to avoid the side effects of systemic corticosteroid before administration of biologics according to the guideline. There has been no direct comparison of efficacy between anti-IL-5 and anti-IL-4Rα antibodies for mucus plugs in patients with asthma, to the best of our knowledge, and prediction of the heterogeneity of mucus plugs might be challenging. A high FeNO level suggests that an IL-13-driven sub-phenotype in type 2 high asthma is one of the biomarkers for poor responders to anti-IL-5 antibody compared with IL-4Rα antibody. In addition, asthma patients with high FeNO levels showed a greater rate of mucus plugging than those with low FeNO levels. These data remind us of the possibility that, if FeNO levels remain high after treatment with anti-IL-5 antibody in asthma patients with mucus plugs, switching to other biologics, including anti-IL-4Rα antibody, might be considered, following the rotation strategy recommended by asthma treatment guidelines. Notably, anti-TSLP antibody decreased mucus plugs for patients with high mucus scores characterized by high blood eosinophil and FeNO levels. The data indicated that anti-TSLP antibody, which blockades the signals of IL-4, IL-5, and IL-13 as a targeting upstream molecule of type 2 cytokines, is another candidate for the treatment of mucus plugs for patients with asthma.
PMC11576441_5	Treatment options for anti-HMGCR IMNM are limited. When glucocorticoid and IVIG treatment are not effective at preventing exacerbation, using efgartigimod to rapidly reduce pathogenic antibody levels for symptomatic relief appears to be a better option than rituximab. Glucocorticoid treatment helps to prevent the immune system from producing further pathogenic antibodies, and IVIG reduces myofiber necrosis caused by complement. Thus, in this particular context, an immediate effect could be achieved by using efgartigimod to quickly remove circulating pathogenic antibodies from the blood.
PMC11576441_3	In seropositive IMNM, the antibody titer correlates with disease activity. The anti-HMGCR antibody titer correlates with muscle strength and CK levels. In vitro and vivo experiments have also shown that anti-HMGCR autoantibody is pathogenic. Moreover, muscle fiber necrosis in IMNM is an antibody- and complement-dependent process. It has been shown that efgartigimod can restore muscle function. Therefore, it is reasonable to hypothesize that lowering the serum anti-HMGCR antibody level could contribute to rapid disease control. Plasma exchange and efgartigimod are two ways to rapidly lower the serum antibody level.
PMC11630930_2	Immunoglobulin G (IgG) is the most common antibody and the main efficacious molecule of humoral immune response.[18] Several types of IgG Fc receptors, including FcRn, are found on the surface of immune cells and play a role in mediating immune responses. The FcRn is an MHC class I-like molecule that recycles IgG, extending its half-life by about 4 times that of other immunoglobulins that are not recycled by FcRn (e.g., IgM or immunoglobulin A).[19] Following cellular uptake, the Fc region of an IgG antibody binds 2 FcRn receptors under acidic conditions in the endosome.[20] IgGs bound to FcRn are rescued from lysosomal degradation and released at physiological pH outside the cell.[5,21–23] The ability to inhibit FcRn and subsequently reduce autoantibody levels provides a novel and targeted approach for treating autoimmune diseases, offering hope for improved therapeutic outcomes.[24] Efgartigimod is a specifically designed molecule that binds to FcRn with high affinity, competing with natural IgG and inhibiting its recycling.[21,22] leading to a reduction in overall IgG levels, offering an effective and well-tolerated treatment option for autoimmune diseases.[25]
PMC11576441_4	Efgartigimod is an FcRn antagonist that competitively binds to FcRn. FcRn is a multifunctional Fc-γ receptor that binds to circulating IgG antibodies, reduces their degradation in lysosomes, and releases them into the extracellular space, thereby prolonging their half-life. Thus, inhibition of FcRn can increase the catabolism of IgG (including pathogenic autoantibodies), providing targeted therapy for immune-mediated diseases, especially those with well-defined pathogenic antibodies. The efficacy of efgartigimod has been demonstrated in a series of clinical trials. Efgartigimod has been used to treat neuromyelitis optica spectrum disorder, Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and stiff-person syndrome.
PMC11324432_0	Efgartigimod is a novel FcRn antagonist that can reduce circulating IgG levels, including pathogenic IgG, and is a drug used to treat IgG-mediated autoimmune diseases. Efgartigimod was approved by the FDA in December 2021 for the treatment of AChR Ab+ MG patients. There is currently no publicly available randomized study on the treatment of AChR Ab+ OMG with efgartigimod. Intravenous efgartigimod was generally well tolerated in patients with MG during the ADAPT study (3). As efgartigimod causes a transient decrease in IgG levels, immunization with live or live-attenuated vaccines is not recommended during treatment (4). The levels of protective antibodies against tetanus toxoid, varicella zoster virus, and pneumococcal capsular polysaccharide decreased along with serum IgG levels with efgartigimod treatment in pemphigus (5). The protective antibodies returned to baseline levels upon cessation of treatment.
PMC11585471_0	Optimal proximal endograft landing in TEVAR is paramount for successful entry tear coverage and favorable aortic remodeling with true lumen expansion. Conventionally, a PLZ in ≥20 mm of healthy aorta is recommended, with inadequate coverage associated with a higher risk of endoleak and potentially lethal retrograde type A dissection (RTAD). However, the proximity of the entry tear to the LSA ostium may warrant a landing zone within the aortic arch, historically necessitating surgical revascularization of the aortic arch. Although an aggressive PLZ with revascularization protects against aortic-related mortality and the need for reintervention when a suitable segment of the healthy aorta is not present in a more distal PLZ, extensive aortic arch debranching carries an inherent risk of complications including embolic stroke and long-term bypass occlusion. Furthermore, proximal endograft deployment in zone 0 (proximal to the origin of the innominate artery) carries a greater risk of technical failure and early postoperative endoleak than PLZ 1 or 2. TEVAR with a single-branched endoprosthesis provides an endovascular alternative to surgical revascularization of the LSA with a zone 2 landing.
PMC11585471_1	Our case highlights several key aspects of branched TEVAR for the treatment of TBAD with an unfavorable anatomy. Although TEVAR with a double-branched physician-modified endoprosthesis could serve as a complete endovascular alternative in this case, multibranched TEVAR carries additional periprocedural concerns. Tazaki et al. observed a periprocedural stroke prevalence of 33% in patients with a double-branched Inoue Stent Graft compared to 7.8% in those with single-branched endografts. Similar outcomes were observed by Czerny et al., with a combined stroke rate of 20% in patients receiving Bolton Relay plus double-branched endoprosthesis. Furthermore, multiple studies have reported a greater risk of RTAD with more proximal endograft deployment, ascending aorta diameter ≥40 mm, and stent-graft oversizing by ≥10%.
PMC11481776_1	Several factors influence bone regeneration after cyst enucleation. One of the most significant factors is the defect size, which plays a crucial role in neo-bone formation [8]. Defects that exceed critical size defects do not restore spontaneously without the assistance of bone grafts, as confirmed by animal experiments as well [9]. Some researchers suggested that bone materials are necessary if the defect length goes beyond 1–2 cm and greater than 50% loss of the perimeter of the bone [10]. The configuration of the defect also impacts bone formation. If the buccal and lingual bone was resorbed by a cyst or removed during surgery, the cavity will not completely recover but fill with fibrous tissue [11, 12]. Other factors include the preservation of periosteum, age, gender, etc. On the contrary, some studies argue that it is unnecessary to place bone grafts due to the strong regeneration capacity of alveolar bone. Complications such as infection and bone fracture after cyst nucleation are quite rare [13].
PMC11505654_3	Bisphosphonate is the most widely used drug to treat GACI. Bisphosphonate is similar to PPi in molecular structure, and it improves the calcification of vessels when administered to patients with GACI with reduced PPi concentrations. The survival rate of patients with GACI who are administered bisphosphonate is 65%, which is much higher than the survival rate of 31% for patients with GACI who are not administered bisphosphonate. As more than half of patients with GACI die within the first month of life, early administration of bisphosphonate is important.
PMC11505654_5	The treatment regimen of bisphosphonate for GACI has not yet been standardized. The commonly used treatment protocols are oral etidronate (20 mg/kg/day), intravenous pamidronate (0.25 mg/kg on day 1 and 0.5 mg/kg on days 2 and 3 for the first course, and 0.5 mg/kg for 3 days as the second course, with courses administered every 2 months), and oral risedronate (1 mg/kg/week). The non-nitrogen-containing bisphosphonate etidronate is a first-generation bisphosphonate and is the most used because of its close structure to PPi. Etidronate, which has a structure similar to PPi, inhibits osteoclast function and has the effect of suppressing calcification. In contrast, nitrogen-containing bisphosphonates, such as pamidronate and risedronate, inhibit the action of enzymes in the mevalonate pathway, thereby suppressing bone resorption by osteoclasts. Etidronate has been shown to inhibit phosphate-induced calcium deposition more potently than nitrogen-containing bisphosphonates. Therefore, for the purpose of improving calcification, etidronate appears to be a better option than other bisphosphonates.
PMC11588313_2	Carcinoid tumours are slow-growing but can metastasize (4%–20%) to local or regional lymph nodes. It is imperative therefore to ensure disease-free margins. Mobilization of the bronchial tree reduces tension when anastomosing the proximal and distal stumps. An intercostal flap can be harvested and wrapped around the bronchial anastomosis and is advisable to give structural support and blood supply.
PMC11608180_3	Daratumumab is an antibody against CD38 used for plasma cell depletion in relapsed or refractory multiple myeloma (MM). It mediates depletion of plasma cells, which overexpress CD38, through a wide range of mechanisms including complement- and antibody-mediated cytotoxicity, Fcy receptor-dependent apoptosis, and modulating immune cell composition [11]. Zand et al. conducted the first clinical trial to explore daratumumab as a treatment in PGNMID, including in treatment-naive disease. Of the 10 PGNMID patients who received daratumumab, 4 entered complete remission (urine protein creatinine ratio < 500 mg/day and eGFR decline < 15%), and 6 had partial remission (at least 50% reduction in baseline proteinuria and eGFR decline < 30%) by 12 months after treatment. Three patients relapsed with partial response after re-initiation of daratumumab. Most patients had obvious reduction in proteinuria by one month after their inaugural infusion [12].
PMC11511746_0	PGNMID occurs most often in the elderly, and the pediatric population is rarely affected [3]. Generally, there are no clear recommendations for the management of PGNMID. Therapy should be directed to the pathological clone, which is identified in only a minority of cases. Conventional immunosuppressive agents (corticosteroids and mycophenolate mofetil), the proteasome inhibitor bortezomib, and the monoclonal antibody rituximab are the commonly used drugs. However, these therapies are often associated with significant side effects and uncertain effectiveness. Daratumumab, a human IgGκ monoclonal antibody targeting CD38, is mainly used in patients with multiple myeloma. In 2021, Zand et al. [4] reported a significant sustained reduction of proteinuria and stabilization of kidney function in 10 adult patients with PGNMID. The drug was administered for 6 months and was well tolerated. Subsequently, Almaani et al. [5] analyzed five adults with bortezomib-resistant PGNMID treated with daratumumab. Four patients demonstrated some improvement—three of them achieved a kidney response, and one showed histological improvement. Previous studies brought to attention that the length of therapy and frequency of daratumumab infusions are not yet clear. Additional research is needed, also in children, to assess the efficacy of daratumumab in patients with PGNMID and to identify the optimal regimen of administration.
PMC11796192_5	The presence of MGRS is grounds for treatment to suppress and eliminate the monoclonal protein causing direct kidney damage. Given the risk of further, potentially irreversible kidney injury we discussed treatment options for the paraproteinemia at length with the patient. Our preference would be to commence treatment with daratumumab, bortezomib and dexamethasone. Additionally, we advocated for a repeat bone marrow biopsy to rule out progression to multiple myeloma and help guide treatment with a daratumumab based regimen.
PMC11417000_5	In terms of immunotherapy, the efficacy of corticosteroids, subcutaneous IFN-γ injections, and intravenous immunoglobulin is limited. However, combination therapy with cyclophosphamide and steroids has shown promising results in some patients (42). Rituximab, an anti-CD20 monoclonal antibody, is one of the most extensively studied biologics in patients with adult-onset immunodeficiency diseases. This medication can eliminate circulating B cells, reduce AIGA titers, restore IFN-γ signal transduction, and improve clinical conditions (37). Bortezomib, a proteasome inhibitor targeting plasma cells, has demonstrated additional suppression of autoantibodies following rituximab failure (44). Combining rituximab with bortezomib is likely necessary to prevent generation of new autoantibody-producing plasma cells (45). Daratumumab, an antibody targeting CD38+ plasmablasts and plasma cells, has further reduced tissue plasma cells, total IgG levels, AIGA titers, and disease progression (46).
PMC11648800_12	Preoperative catheter embolization of the arterial feeder is utilized to reduce the risk of bleeding, especially in cases where there is deep implantation into the hepatic parenchyma. While postoperative hepatic artery embolization has limited efficacy in controlling hemorrhage, preoperative arterial embolization may yield better outcomes. Another option involves postoperative methotrexate administration, particularly in cases where the placenta is left in situ or there is a rise in serum human chorionic gonadotropin (HCG) levels despite resection, or intraoperative injection of methotrexate directly into the sac in cases of unresectable pregnancy. Methotrexate facilitates the expedited degeneration of residual trophoblastic tissue. Additionally, preoperative administration of mifepristone is employed in certain cases, as it has demonstrated improved cure rates when combined with methotrexate in ectopic pregnancies. Mifepristone acts by reducing vascularity and inducing degeneration and necrosis of villi.
PMC11461946_1	Traditional management of OCSDH typically involves a large craniotomy with hematoma removal and durotomy. While aggressive surgery involving total removal of the abnormal proliferative membrane and hematoma is effective, this approach is highly invasive. It carries significant risks, including infection, bleeding, general anesthesia and prolonged recovery, particularly in elderly patients or those with comorbidities. The dual approach of MMAE and minor surgery represents a novel minimally invasive treatment for OCSDH, combining reducing the hematoma's blood supply with less invasive hematoma evacuation.
PMC11461946_0	OCSDH represents a complex progression of CSDH, characterized by a thick, vascularized membrane surrounding the hematoma. This neovascularization and membrane formation contribute to the persistence and resistance of the hematoma. Factors such as inflammation, angiogenesis, and coagulopathy are believed to play key roles in the pathogenesis of recurrent CSDH and OSCDH. Managing OCSDH poses significant challenges, particularly because the condition often requires more invasive therapeutic interventions than standard CSDH. On the other hand, MMAE has recently gained attention as a less invasive treatment for recurrent or refractory CSDH. By reducing the blood supply, MMAE helps to shrink the hematoma and prevent its recurrence. Previous studies report a recurrence rate of 8%–30% with burr hole surgery alone, compared to 2.7%-5.4% with the addition of MMAE. In addition to the lower recurrence rate, the benefits of additional MMAE include reduced intraoperative blood loss and shorter hospital stays. These advantages are particularly relevant for elderly patients or those with comorbidities and antithrombotic therapy who are at high risk of recurrence. Moreover, from its previously mentioned pathophysiological perspective, MMAE is reasonable as a curative treatment for CSDH. Therefore, this novel technique could be helpful for patients with OSCDH with a thick, neovascularized membrane.
PMC11569471_0	Chronic subdural hematomas (cSDH) have traditionally been treated via burr hole evacuation or craniotomy, but there is a high rate of recurrence, ranging from 10–20%. Additionally, mortality rates of cSDH at 6 and 12 months have been estimated to be 30%. More recently, embolization of the MMA has been used in the setting of cSDH. The MMA supplies approximately 2/3 of the cranial dura. MMA embolization has been used as a primary treatment or as a surgical adjunct. Larger studies have shown 85–98% success (no recurrence) with ∼70% having 50% reduction in cSDH size.
PMC11789874_6	Middle meningeal artery embolization is a surgical procedure that reduces dural blood supply, inhibits neovascularization, suppresses inflammatory mediator release, and prevents hematoma formation and recurrence to achieve therapeutic goals.[27] While middle meningeal artery embolization has demonstrated efficacy in chronic subdural hematoma, its initial onset is not prevented.[28] In OCSDH, characterized by a lack of liquid components within the lesion, the clinical effectiveness of inhibiting neovascularization to reduce exudation or hemorrhaging is limited. Additionally, the blood supply to the lesion originates not only from the dura mater but also from the lesion’s visceral layer, raising questions about the standalone efficacy of middle meningeal artery embolization in treating OCSDH. Nonetheless, some studies suggest that middle meningeal artery embolization can reduce perioperative bleeding risk and postoperative recurrence during craniotomy.[6,29] It is important to note that middle meningeal artery embolization targets the middle meningeal artery specifically and does not directly address the mass effect of the lesion. The therapeutic effects of middle meningeal artery embolization are typically delayed post-surgery and may be restricted in patients with acute and severe clinical presentations. Furthermore, there is a lack of consensus regarding target vessel selection, protection of anastomotic branches, and the choice of embolization materials for middle meningeal artery embolization, highlighting the need for further research. It is crucial to remain vigilant against potential complications such as visual impairment, hemorrhage, infarction, allergies to contrast agents, and catheter-related issues.
PMC11461946_2	While our results were positive, larger studies are needed to confirm the efficacy and safety of combining MMAE with minimally invasive surgery for OCSDH. Although OCSDH is a rare disease, future research should focus on comparing outcomes between this combined less invasive approach and traditional large craniotomy with MMAE. Additionally, exploring using different embolic agents or supplementary therapies, such as endoscopic surgery, could further optimize outcomes. Developing standardized protocols for the management of OCSDH with MMAE might significantly advance clinical practice and improve patient care.
PMC11587153_0	Typically, oral migraine preventive medications are effective for migraine auras without headaches; however, some patients tend to exhibit resistance to these therapies. In such cases, the use of CGRP mAb is considered an alternative treatment option, with reasonable evidence supporting its efficacy not only in reducing migraine attacks but also in alleviating associated migraine auras and photohypersensitivities. There is also a study indicating that the use of CGRP mAb may improve sleep in patients with migraines.
PMC11794975_5	The great effectiveness of galcanezumab in reducing both pain and aura symptoms may suggest that CGRP has an important biological role in HM, MA, and PRRT2‐associated FHM.
PMC11794975_1	CGRP is a vasoactive neuropeptide that is widely expressed in both central and peripheral nervous systems. Previous studies have attempted to investigate the relationship between CGRP and cortical spreading depression (CSD) in the genesis of migraine aura. Some authors suggest that the increase of extracellular potassium levels observed during CSD promotes release of cortical CGRP. In addition, experimental models have demonstrated that the depolarization occurring during CSD leads to stimulation and upregulation of CGRP in several brain regions in rats. Moreover, other studies showed that blockage of CGRP receptors in vitro is able to inhibit genesis of CSD. A recent study showed that infusion of CGRP triggered aura in people with MA within 12 h of the administration, suggesting that CGRP can trigger CSD, possibly by activating nociception pathways and stimulating the visual cortex and other CSD‐susceptible areas.
PMC11587153_5	A basic study has reported on the inhibitory effects of CGRP mAb and gepant on CSD. Cortical slice studies showed that the blockage of CGRP receptors in vitro resulted in the inhibition of CSD. CGRP mAbs do not cross the blood–brain barrier. Therefore, they are thought to act on the trigeminal nerve outside of this barrier.
PMC11587153_2	There is abundant evidence that CSD is responsible for neuronal inflammation and the activation of the central and peripheral trigeminal nerves in migraines. During CSD, neurons, glia, and vascular cells locally release adenosine triphosphate (ATP), glutamate, potassium, and hydrogen ions, while activated perivascular nerves release CGRP and nitrous oxide. CSD also opens neuronal pannexin1 (Panx1) mega channels, triggering the release of caspase-1 and high-mobility group box 1 (HMGB1) from neurons and activating nuclear factor kappa B (NFκB) in astrocytes. These pro-inflammatory molecules diffuse toward the cortical surface, activating pial nociceptors, which lead to neurogenic inflammation, persistent activation of dural nociceptors, and the subsequent stimulation of central trigeminal neurons in the trigeminal spinal nucleus. The release of these inflammatory neurotransmitters, including CGRP, into the subarachnoid space has been discussed as the cause of migraine headache. Additionally, CSD events significantly increase CGRP messenger ribonucleic acid (mRNA) levels in the rat cerebral cortex. This is one of the mechanisms that initiate and maintain elevated CGRP levels in migraine and other conditions such as post-traumatic headache.
PMC11857675_24	Corticosteroids are the first-line treatment for irAEs, including myocarditis. Guidelines from the European Society of Cardiology (ESC) and the European Society for Medical Oncology (ESMO) recommend initiating high-dose corticosteroids (e.g., methylprednisolone) for the first few days, followed by a gradual reduction in dosage. The Society for Immunotherapy of Cancer (SITC) and the American Society of Clinical Oncology (ASCO) also recommend high-dose corticosteroids for confirmed or highly suspected myocarditis.
PMC11625816_6	Early administration of corticosteroids has demonstrated good efficacy, potentially helping to prevent the rapid progression of multi-organ irAEs. Currently, treatment protocols for ICI adverse reactions remain controversial, particularly in conjunction with subsequent tumor therapies. Photodynamic therapy may represent a promising option, as it not only synergistically enhances the efficacy of immunosuppressants in significantly inhibiting tumors but also provides beneficial effects in alleviating ICI-induced adverse reactions.
PMC11349625_4	In general, irAE has been managed with ICI discontinuation and systemic corticosteroid administration. If improvement is limited, immunosuppressive agents may be administered as the next treatment (13, 14). In previous reports, four out of six cases achieved remission with only discontinuation of ICIs and systemic corticosteroids ( Table 1 ). In half of the reports, the treatment started with intravenous administration of methylprednisolone (500-1000 mg/day), followed by tapering to prednisolone (0.5-1 mg/kg/day). Further studies are warranted to establish the treatment strategy for irAE IgA vasculitis, which is relatively rare.
PMC11625816_4	Photodynamic therapy may serve as an important adjunctive treatment following ICIs. Existing clinical data indicate that photodynamic therapy can significantly inhibit tumor progression and is one of the important palliative treatments for advanced stages of the disease, often serving as adjuvant therapy following radiotherapy, chemotherapy, and immunotherapy. Recent foundational studies have demonstrated the efficacy of combining ICIs with PDT. PDT enhances local dendritic cell cross-presentation of tumor antigens and induces immunogenic cell death (ICD) in tumor cells, thereby mediating CD8+ T cell immune responses. The use of ICIs inhibits Treg cells, further enhancing the immune response facilitated by PDT. On the other hand, various photosensitizers used in photodynamic therapy can increase tumor sensitivity to PD-L1 antibody checkpoint inhibition, thereby enhancing the immune response against the tumor. The synergistic mechanisms of PDT and ICIs are related to the enrichment of immune cells and the formation of immune memory. Existing studies suggest that their combination may promote immune cell infiltration by altering the expression of ALAS2, ITGA10, and ADAM12. This activation of tumor immune memory can lead to the destruction of tumor cells while simultaneously inhibiting distal tumor growth and preventing metastasis and recurrence.
PMC11700999_7	At present, the management of irAEs predominantly relies on clinical expertise and is conducted in accordance with the grading criteria established by the Common Terminology Criteria for Adverse Events (CTCAE). For grade 1 adverse events, specific therapeutic interventions are generally unnecessary, allowing for the continuation of immunotherapy. In the case of grade 2 adverse events, it is recommended to suspend ICIs treatment until symptomatic improvement is observed, with some patients potentially necessitating corticosteroid therapy. Patients who experience grade 3 or 4 adverse events typically require corticosteroid treatment and may need to either temporarily or permanently discontinue ICIs therapy.
PMC11484190_3	To ensure the safe use of cetuximab, we recommend a thorough assessment of the patient’s history of drug and food allergies, as well as any autoimmune diseases, before initiating treatment. In well-equipped centers, it is advisable to conduct pre-treatment drug skin tests [13] or measure specific immunoglobulin E (IgE) levels, such as those for galactose-alpha-1,3-galactose (alpha-Gal) [14]. If the skin test or IgE levels are positive, it strongly indicates a high likelihood of an allergic reaction. For these high-risk patients requiring cetuximab, ensure thorough premedication or consider directly using a desensitization protocol. Additionally, cetuximab should be administered in centers that have emergency equipment and experienced staff to ensure patient safety.
PMC11382217_1	Rapid recent advancements in extracorporeal circulation support technology have led to the development of ECMO, which has been successfully applied in the treatment of pheochromocytoma crisis.2,5 The most common mode is VA-ECMO because it provides full circulatory support and improves tissue oxygenation in situations of cardiogenic shock combined with severe pulmonary edema.6,7 Rapid reversibility makes severe cardiac dysfunction induced by pheochromocytoma and paraganglioma that is refractory to drug therapy a perfect indication for extracorporeal circulatory support. 8 In such cases, VA-ECMO might be the only way to prevent death. 5
PMC11549947_5	Approximately 10% of patients with takotsubo syndrome develop cardiogenic shock requiring mechanical support to maintain cardiac function [5,20]. VA-ECMO is recommended to ensure adequate cardiac output and support cardiac function as a bridge until ventricular function improves, as takotsubo syndrome is transient and reversible. The use of an intra-aortic balloon pump in this condition is generally avoided as it can worsen one of the possible complications of takotsubo syndrome – LV outflow tract obstruction [5].
PMC11705711_6	The successful use of ECMO therapy is a notable feature, showing its vital role in stabilizing hemodynamics and managing refractory ventricular arrhythmias. This case underscores the importance of early ECMO intervention in cases where conventional therapies fail, providing essential circulatory support and improving patient outcomes in life-threatening situations.
PMC11315265_4	VA ECMO support becomes necessary in these cases of malignant sustained forms of arrhythmia and hemodynamic instability, and also a back-up for high-risk therapeutic interventions, which is also supported by a case series of Baratto et al.[10] The main effect of VA ECMO is to maintain perfusion and oxygenation of the body during VT or cardiac arrest and, therefore, protects the brain and the heart throughout the procedure.
PMC11393609_1	In patients with pheochromocytoma, cardiovascular and neurological manifestations usually dominate the clinical picture, with 95% of patients having hypertension and 90% having headaches at presentation [7–9]. Hypertension is either sustained (50%) or paroxysmal (45%) and is more commonly associated with norepinephrine-secreting tumors. Further, postural hypotension in patients with pheochromocytoma is uncommon. Although, the exact etiology is unclear, postural hypotension is most probably precipitated due to the fluctuation in vascular tone, suppression of baroceptor signaling, and/or hypovolemia and/or downregulation of adrenergic receptors [10–14]. Other severe cardiovascular manifestations include arrhythmia, hypotension, shock, myocardial ischemia, cardiomyopathy, aortic dissection, and extremity ischemia [15]. Investigations usually reveal LV dysfunction of varying severity, with regional wall motion abnormalities that are global or present in the distribution of multiple coronary arteries, elevated myocardial enzymes, and ECG abnormalities [4,16]. The diagnosis of pheochromocytoma-induced TLC is based on the International Takotsubo Diagnostic Criteria or Mayo diagnostic criteria [17,18]. Pheochromocytoma-induced TLC is more commonly reported in norepinephrine-secreting tumors. It has been proposed that catecholamines, especially norepinephrine, increase myocardial oxygen demand, induce microvascular dysfunction, and induce severe epicardial coronary vasospasm [19,20]. Furthermore, excess catecholamines, especially norepinephrine, are oxidized and produce a direct toxic effect on the myocardium by increasing the sarcolemmal permeability and cellular calcium influx. This results in reduced myocyte viability, cardiac contractility, and distortion of the conductive system. All of these can induce cardiomyopathy, myocardial ischemia, and various EKG changes, including deep symmetric T-wave inversion, prolongation of QT interval and ST-T segment abnormalities, and arrhythmias [5]. Importantly, all these changes are reversible and resolve after the administration of phenoxybenzamine and resection of pheochromocytoma [4,5,21]. Furthermore, recurrence of pheochromocytoma-induced TLC after adrenalectomy has never been reported [15,22].
PMC11453165_0	Tetracycline, known for its broad-spectrum antimicrobial activity, is a valuable adjunct in periodontal therapy. Effective against Gram-positive bacteria, spirochetes, and various anaerobic and facultative bacteria, tetracycline achieves high concentrations in gingival crevicular fluid, enhancing its efficacy in periodontal treatment. Beyond its antimicrobial properties, tetracycline inhibits collagenase, reducing collagen breakdown in periodontal disease, and has been shown to possess anti-inflammatory effects, inhibit bone resorption, and promote fibroblast attachment. These multifaceted benefits make tetracycline a promising addition to non-surgical periodontal therapies. Various systems for delivering tetracycline to periodontal pockets exist, including fibers and films. The "Periodontal Plus AB™" system, combining tetracycline HCL with fibrillar collagen, offers a novel approach.
PMC11453165_3	PBMT demonstrated positive effects on periodontal healing in preclinical and clinical studies, including enhanced angiogenesis, fibroblast activity, and reduced inflammation. The variability in PBMT parameters across studies highlights the need for standardized protocols. While promising, further research is necessary to optimize PBMT parameters and establish its definitive role in periodontal therapy.
PMC11453165_2	In this case presentation, combining tetracycline fibers with SRP led to significant clinical improvements in periodontal parameters and a gain in clinical attachment levels. The tetracycline fibers showed efficacy after thorough subgingival debridement, suggesting their antimicrobial and anti-collagenase properties contribute to positive outcomes. Potential side effects of tetracycline fibers, such as allergic reactions and discomfort, need consideration. Moreover, a limitation of tetracycline use in medically compromised patients paves a new treatment modality as an adjunct to SRP.
PMC11332970_11	According to their findings, the wound area treated by LLLT significantly improved, and pro-healing factors, including vascular endothelial growth factor (angiogenesis) and TGF increased, while TNF (a pro-inflammatory factor) dropped. These findings imply that the improvement brought about by LLLT can be linked to elements that speed up the healing of wounds [26].
PMC11453165_4	Overall, both tetracycline fibers and PBMT demonstrated potential as adjuncts to SRP for managing periodontitis. The results highlight that non-surgical treatments, rather than surgical ones, may alter patient preferences by avoiding the pain often associated with surgical periodontal procedures, which many people fear and thus frequently avoid. This case emphasizes the need for personalized non-surgical treatment approaches and calls for further research to refine and validate these modalities for long-term clinical application.
PMC11611897_7	Satralizumab may be a safe and efficient adjunct therapy which can be used in the acute stage of the refractory DON which shows poor or no response to steroid pulse therapy. However, a large-scaled randomized control study is needed to further evaluate the necessity and efficacy of satralizumab in acute-staged DON therapy.
PMC11611897_5	Although most post-vaccination DON shows good response to steroid pulse therapy, there exist a few case reports indicating that some AQP-4 Ab seropositive or AQP-4 Ab and MOG-Ab dual seronegative cases showed poor or no response to steroid pulse therapy, and needed other adjunct therapies such as plasma exchange or immunoadsorption to rescue their vision (7–10). However, if plasma exchange or immunoadsorption therapy is not available, for example, because of plasma shortage, unaffordable expenses, or allergic reaction, monoclonal antibody such as rituximab and satralizumab is an alternative for adjunct therapy for the refractory DON and NMOSD (15, 16).
PMC11648988_2	Safety is the most important concern when selecting therapies for pregnant patients with DON. Methylprednisolone and prednisone have been proven to be safe for both pregnant women and their fetuses. However, mycophenolate mofetil and methotrexate are contraindicated in pregnant patients due to their teratogenic potential. Azathioprine and rituximab are considered relatively safe during pregnancy and lactation since their side effects have been rarely reported in the literature. Previous studies have revealed that azathioprine may occasionally lead to miscarriage, infection, anemia, neutropenia, lymphopenia, or even congenital abnormalities such as ectrodactyly. In contrast, rituximab may rarely cause premature labor, infections, lymphopenia, neutropenia, or congenital abnormalities. Currently, there is still a lack of safety data regarding the use of inebilizumab in pregnant patients with DON. Given that inebilizumab is mechanistically and pharmacologically very similar to rituximab, its safety profile during pregnancy may also be quite similar. Current clinical experience indicates that satralizumab and tocilizumab appear to have favorable safety profiles during pregnancy and lactation. As a monoclonal antibody specific to the interleukin-6 (IL-6) receptor, IgG2-formed satralizumab, compared to IgG1-formed tocilizumab, may be much safer for DON cases during pregnancy and lactation. A case report revealed that satralizumab has a longer plasma half-life and lower placental passage and transfer compared to tocilizumab. Hence, satralizumab may be safely used during pregnancy and breastfeeding. However, transient neutropenia, particularly severe febrile neutropenia, although rare, has been reported in previous studies.
PMC11225426_0	TURP was found to be safe in surgery for benign prostatic hyperplasia (BPH) and still means the gold standard for managing benign prostatic hyperplasia [1, 2, 15]. Technical options such as bipolar and laser treatments may further minimize the risks of this procedure [1, 2]. Three kinds of surgery for benign prostatic hyperplasia (BPH), transurethral resection of the prostate (TURP), laser vaporization of the prostate (LVP), and laser enucleation of the prostate (LEP) were found to be safe [15]. Severe postoperative complications are associated with increased surgery duration and increased morbidity was found in patients with a resection time of more than ninety minutes, gland size of more than forty-five grams, and patient age greater than eighty years old [17, 18]. On multivariate analysis, the surgery of transurethral resection of the prostate (TURP) lasting longer than ninety minutes had higher chances of mortality, sepsis, myocardial infarction, venous thromboembolism, and failure to wean from the mechanical ventilator [15–17]. This surgical complication, although rare, can be avoided by taking precautions [19]. Accurate preoperative judgment of the size of the adenomas for predicting the expected resection weight and duration of the surgery is appreciatively desirable [20].
PMC11705096_3	The management of CAD involves a multifaceted approach to optimise patient outcomes. Clinical guidelines from various organisations recommend a combination of medical therapy, cardiac rehabilitation, and revascularisation with either PCI or CABG based on individual circumstances. There is ongoing debate regarding the effectiveness of PCI versus CABG in improving outcomes for patients with CAD. The choice of either PCI or CABG is dependant on several factors, including the severity and complexity of CAD, symptoms and co-morbidities. A meta-analysis of 17 randomised controlled trials (RCTs) comparing PCI to CABG found that both interventions had similar rates of major adverse cardiovascular events (MACE) at twelve months (49,50). In contrast, a meta-analysis of 24 RCTs indicated that CABG was associated with lower rates of MACE at five years compared to PCI, suggesting that CABG may be more beneficial for long-term outcomes (51). Furthermore, a recent study found that CABG was associated with better long-term outcomes compared to PCI in patients with multiple-vessel CAD or left-main stem disease (48).
PMC11608458_2	The identification of antibiotic susceptibility in A. ursingii reveals resistance to the most common cephalosporins (cephalothin, cefotaxime, cefixime, and moxalactam) and furans. However, they are susceptible to amoxicillin-clavulanate, ticarcillin-clavulanate, piperacillin-tazobactam, imipenem, aminoglycosides, ciprofloxacin, tetracycline, sulfamide, and colistin. A. baumannii, which is the most common Acinetobacter species, may present lower rates of antimicrobial resistance with better outcomes. Furthermore, patients infected with A. ursingii had much lower 28-day mortality than those infected with A. baumannii did (6% vs. 37%), even though multidrug resistance and inadequate initial treatment were equally likely in patients infected with either species, indicating lower virulence and, consequently, lower mortality rates.
PMC11583576_5	Thorough cleaning significantly alleviates inflammation and prevents the spread of infection, demonstrating clear benefits over open debridement [20, 25]. Thorough arthroscopic lavage and debridement are currently safe and effective methods for the treatment of septic arthritis, but these methods are characterized by rapid, minimally invasive recovery [16, 20, 25]. After infection control, patients generally recover within 6 weeks to several months [7], which is a better prognosis than other types of septic arthritis and may be attributed to its lower degree of invasiveness. Early in purulent arthritis, cartilage destruction can occur, making the selection of appropriate antibiotics to control infection a key factor in the treatment of bone and joint infections [16, 24]. Gemella morbillorum has been shown to be susceptible to most β-lactams, particularly vancomycin. However, there are different degrees of resistance to cefoxitin, macrolides, tetracyclines and quinolones [13, 14].
PMC11583576_6	Second, arthroscopic debridement should be performed early, and full-doses of antibiotics should be used to prevent bone damage. Once bone erosion and cartilage damage have started, a second-stage arthroplasty is the only solution.
PMC11509662_0	Acute SA of a native joint is one of the most critical orthopedic urgencies. It can affect all synovial joints, although data show that about 50% of cases involve the knee, and S. aureus is the most common pathogen. The physiopathology of joint damage is multimodal, with both infection itself and joint inflammatory response representing the key elements of it. Particular attention must be paid to all procedures that require access to the articular chamber, mainly if performed outside a sterile setting, since a communication is created between the synovial cavity and the external environment. Among these procedures, viscosupplementation with HA and GCs injections are a common practice in the conservative management of symptomatic osteoarthritis. However, intra-articular injections, as well as all diagnostic and therapeutic practices that involve piercing the skin, can bring microorganisms from the skin into the joint, contaminating it and eventually leading to SA. SA of a native joint represents the most dangerous complication of intra-articular injection, despite a reported low incidence rate (as “higher” as less than 1/1,000). SA can cause enormous joint damage, which can lead to irreversible alterations of the joint structures with consequent disability, even leading to the patient’s death by sepsis. Early identification and appropriate treatment—consisting of combined surgical debridement and systemic antibiotic therapy—are of paramount importance. A timely and accurate synovial debridement aiming to remove as much infected material as possible is key to success, and it can be performed with both arthrotomic or arthroscopic techniques. Recent studies have shown similar effectiveness of open surgery and arthroscopically procedure in eradicating an infection of a native knee, even though arthroscopic treatment was associated with lower complication rate and better functional recovery. Methylene blue has demonstrated its ability to stain infected, nonviable, and inflammatory host tissues, and it has been used as an effective debridement guide in the intra-operative setting.
PMC11509662_2	The concept of topical antibiotic therapy appeared before the 1970s when molecules of different antibiotic concentrations were locally administered “naked”. This concept was taken up and developed with the studies of Buchholz and Engelbretch on the use of antibiotic-loaded polymethylmethacrylate (PMMA) in the treatment of periprosthetic joint infections (PJIs), and then further evolved with calcium-based carriers, hydroxyapatite, or bioactive glass. The local use of calcium sulfate spheres loaded with antibiotics has been widely studied for the prevention and treatment of multiple infectious conditions, including osteomyelitis and PJIs, but also for soft tissue diseases or preventive purposes in risky situations. However, the indications for its use have expanded to also include post-operative infections following closed and open fractures, spontaneous bone infections, and native joint infections. These carriers include a known elution profile, reabsorbability, ability to fill the dead space, and versatility in application (e.g., beads of different dimensions or as bullets or a paste). Although antifungal-impregnated PMMA beads have been described for fungal septic arthritis of a native joint, there are concerns about traditional antibiotic therapies, such as hepato- or nephro-toxicity, and the risks associated with systemic administration. Calcium sulfate carriers significantly reduce these risks, providing a safer alternative. A further reason for choosing these substances in cases of septic arthritis is their ability to actively act against biofilm, which presents antibiotic resistance significantly higher than free-floating microorganisms. Calcium-based carriers allow adequate minimum inhibitory concentration and minimum biofilm eradication concentration values to be achieved and maintained for several weeks. The literature available regarding the use of antibiotic carriers in cases of periprosthetic infection is extensive, covering various methodologies including debridement and implant retention.
PMC11432800_2	Additionally, the role of PRP in accelerating the healing process of traumatic wounds and ulcers is well-established, with benefits stemming from the high concentration of platelet-derived growth factors enhancing tissue repair and angiogenesis.
PMC11432800_1	The primary advantage of this technique lies in the rich presence of connective tissue cells within the stromal vascular fraction of adipose tissue, which includes a diverse cell population such as preadipocytes, endothelial cells, monocytes, macrophages, granulocytes, lymphocytes, and notably, adipose-derived stem cells (ADSCs). These cells are integral to promoting wound healing through mechanisms like enhanced cellular proliferation, differentiation, reduced inflammation, and improved vascularization.
PMC11557112_1	PRP may act as a regulatory factor for cell migration and wound healing, promoting the migration of MSCs and the process of wound repair. PRP may provide a suitable microenvironment for MSCs to promote their proliferation and differentiation. The combination of MSCs and PRP may also increase the number of fibroblasts and keratinocytes in the wounded skin. Fibroblast healing, remodeling of injured skin, and migration of keratinocytes can promote re-epithelialization through the healing process. This increased expression may promote the synthesis of collagen and integrins in fibroblasts and increase the migration of epithelial cells. MSCs and PRP can induce stronger angiogenesis responses in wound healing. PRP combined with MSCs may represent a promising approach to the treatment of wound healing.
PMC11605738_4	Mirtazapine administration also resulted in modest improvements in psychotic symptoms, with mild sedation being the sole reported adverse effect. A comprehensive systematic review and meta-analysis evaluated the global akathisia score for 10 medications used to treat AIA across 15 clinical trials involving 492 participants. The investigation revealed that mirtazapine, vitamin B6, and biperiden had the three most promising efficacy and tolerability profiles. Mirtazapine ranked highest in both the primary analysis and all subgroup assessments.
PMC11605738_3	Mirtazapine, a tetracyclic antidepressant, inhibits central presynaptic alpha-2-adrenergic receptors, thereby enhancing serotonin and norepinephrine release. Classified as a noradrenergic and specific serotonergic antidepressant, it antagonizes H1 histamine receptors and 5-HT2A, 5-HT2C, and 5-HT3 serotonin receptors, resulting in sedative and anxiolytic effects. Its potent presynaptic alpha-2 adrenergic antagonism underlies its antidepressant action, while significant 5-HT2A blockade at low doses contributes to its anti-akathisia properties.
PMC11545733_13	Treatment of the patients, in most cases, included rectal resection combined with chemoradiotherapy based on 5-fluorouracil. In more recent studies, the authors used polychemotherapy regimens such as FOLFOX and FOLFIRI, as well as regimens involving monoclonal antibodies (bevacizumab, cetuximab) and targeted therapy (regorafenib, vemurafenib).
PMC11541487_0	Adequate proximal seal zones are essential for durable endovascular aortic repair. Although the definition of an adequate proximal seal zone can vary depending on the underlying aortic pathology, compromised proximal seal zones during TEVAR are associated with increased aortic- and device-related events such as type IA endoleak and device migration. Introduction of TBE into the array of commercial TEVAR options has allowed more complex aortic arch pathologies to be treated using endovascular or hybrid approaches, avoiding open arch reconstruction and the need for circulatory arrest. However, like any other TEVAR, TBE is not immune to proximal failures.
PMC11572399_3	Recent research on treating UUTUC has focused mainly on neoadjuvant chemotherapy, postoperative chemotherapy, and immunotherapy. For high-grade UUTUC patients with preoperatively obtained pathological evidence, the prospective data from a phase II trial show that the use of preoperative neoadjuvant chemotherapy can achieve a 14% pathological complete remission rate [25]. Compared with surgery alone, neoadjuvant chemotherapy can reduce the recurrence rate and mortality without causing adverse effects on subsequent surgery [26] and improve progression-free and overall survival [27]. A meta-analysis showed that neoadjuvant chemotherapy resulted in a pathological partial response rate of 43% and a downstaging rate of 33% and improved overall survival and cancer-specific survival over radical nephroureterectomy alone [28]. Patients with invasive UUTUC who received gemcitabine-platinum combination chemotherapy within 90 days after radical surgery had significantly longer disease-free survival than those who underwent postoperative follow-up alone [29]. However, the efficacy of postoperative chemotherapy was strongly correlated with the variant histology; only patients with pure UUTUC showed a significant improvement in overall survival, whereas UUTUC patients with squamous differentiation and sarcomatoid metaplasia showed no improvement [30]. A study showed that nivolumab significantly improved the disease-free survival of patients with high-grade invasive urothelial carcinoma after radical surgery to 20.8 months, while the survival in the placebo group was only 10.8 months [31]. Therefore, immunotherapy might be a valid choice for the postoperative treatment of UUTUC.
PMC11499491_0	Surgical techniques to treat SVAS have developed from simple procedures to complicated reconstructions of the aorta. The earliest technique was McGoon’s single-sinus diamond-shaped patch repair and in 1977, Doty’s 2-sinus inverted bifurcated patch aortoplasty technique was invented. In 1988, Brom started 3-sinus repair, using three patches to reconstruct each aortic sinus. In 1993, Meyers invented an autologous slide-aortoplasty technique. Brom’s 3-sinus repair have gained in popularity because it can repair sinuses flexibly compared with 1- and 2-sinus repairs. It is important not only to release the stenosis but also repairing the sinuses of Valsalva; creating the three sinuses equally will reconstruct more functional valve and contribute to long-term results. Brom’s aortoplasty promotes the restoration of normal aortic root geometry and relief of coronary ostial stenosis, which is important in preventing myocardial ischemia.
PMC11636330_1	The anatomical and physiological characteristics of children are different from those of adults. Firstly, the urethra and ureteral in children are slender and often associated with anatomical abnormalities, making retrograde ureteral catheterization more prone to ureteral injury and increases the risk of postoperative ureteral stricture. Secondly, children have smaller kidney volumes, smaller renal space, and lower tolerance to increased renal pressure. Children also have smaller blood volume and poorer thermoregulatory capacity. The increased renal pressure caused by artificial hydronephrosis can easily lead to the displacement of colonizing bacteria, resulting in systemic infection.
PMC11524652_1	Breathing exercises included pursed-lip, segmental, and diaphragmatic breathing, which improved ventilation by forcing airway back pressure. A randomized control trial conducted on oral cancer patients by Satish et al. stated that the 6MWT is closely linked to VO2 max, which makes it a reliable assessment tool for cancer patients. Pathan et al. conducted a study on the physiotherapy approach toward reconditioning of patients with empyema that concluded breathing exercises help in improving lung function. Lung expansion techniques and an active cycle of breathing techniques led to decreased dyspnea in patients.
PMC11856888_0	In recent years, the treatment of lymphoma has changed significantly from traditional nonspecific anti-proliferative chemotherapy to targeted therapy of specific molecular signaling pathways combined with traditional chemotherapy. Monoclonal antibodies, protease inhibitors and immunomodulatory drugs play an important role in the treatment of lymphoma.[7] With the in-depth study of lymphatic tumor signaling pathway inhibitors, drugs such as Bruton’s tyrosine kinase are also providing new treatment ideas. Tyrosine kinase is the central mediator of B cell receptor signaling and is required for normal B cell development.[8] In vitro and in vivo experiments show that BTK inhibitors are effective against lymphoid tumors such as chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, DLBCL and multiple myeloma.[9,10] BTK inhibitors can cross the blood-brain barrier and are well distributed in the central nervous system (CNS), where they can effectively inhibit B-cell proliferation and promote apoptosis.[8] In a phase II study evaluating the efficacy and safety of ibrutinib in relapsed or refractory CNS lymphoma, 23/31 (74%) of patients with primary CNS lymphoma and 9/15 (60%) of patients with secondary CNS lymphoma achieved clinical remission, with 12 and 7 CRs, respectively. This study confirmed the single-agent efficacy of ibrutinib in relapsed/refractory CNS lymphoma.[11]
PMC11523029_0	According to Soliman et al., intrauterine infusion of PRP could boost implantation and pregnancy outcomes in recurrent implantation failure (RIF) patients; thus, clinicians should consider this intervention a constructive approach in assisted reproductive procedures. Endometrial thickness is the most crucial factor in IVF, followed by a high-quality embryo. When following a preparatory protocol, fresh and frozen embryo transfers could achieve the required endometrial thickness of over 7 mm. Certain patients whose live birth rate was lower but still acceptable should have been recommended to move forward with the embryo transfer even if they could not acquire an endometrial thickness in many preparation cycles.
PMC11809048_13	In addition, chemotherapy with temozolomide and capecitabine (TC regimen) has shown promising results, though its use has only been reported in a few case reports. The response rate to the TC regimen was 39.7%, and both progression-free survival (PFS) and overall survival (OS) improved [36].
PMC11596955_1	Simultaneous implant placement with GBR is a widely accepted technique to manage implant placement in areas with insufficient bone volume. The aim of GBR is to enhance bone volume, ensure the stability of the implant, and improve the aesthetic outcomes. In the literature, several studies investigated the long-term performance and success rates of implants placed with GBR, comparing different materials and techniques.
PMC11562316_0	Labially impacted maxillary canines have a slight prevalence compared to palatally impacted canines and are typically attributed to insufficient arch span. A variety of techniques have been proposed to treat impacted canines, including space recreation, orthodontic mechanical eruption, extraction, and interceptive approaches. There are three potential reasons for immobility during orthodontic therapy: presence of bone surrounding the impacted crown, improper orthodontic mechanics, and ankylosis. If forced eruption of the impacted tooth is ineffective, alternative prosthetic solutions such as transalveolar extraction succeeded by immediate implant insertion or fixed or removable prostheses should be evaluated.

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🔭 Overview

R2MED: First Reasoning-Driven Medical Retrieval Benchmark

R2MED is a high-quality, high-resolution synthetic information retrieval (IR) dataset designed for medical scenarios. It contains 876 queries with three retrieval tasks, five medical scenarios, and twelve body systems.

Dataset	#Q	#D	Avg. Pos	Q-Len	D-Len
Biology	103	57359	3.6	115.2	83.6
Bioinformatics	77	47473	2.9	273.8	150.5
Medical Sciences	88	34810	2.8	107.1	122.7
MedXpertQA-Exam	97	61379	3.0	233.2	154.9
MedQA-Diag	118	56250	4.4	167.8	179.7
PMC-Treatment	150	28954	2.1	449.3	149.3
PMC-Clinical	114	60406	2.2	182.8	480.4
IIYi-Clinical	129	10449	3.5	602.3	1273.0

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Github link R2MED

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