Valve-in-Valve Transcatheter Aortic Valve Replacement Versus Redo-Surgical Aortic Valve Replacement in Patients With Aortic Stenosis: A Systematic Review and Meta-analysis.

Aortic stenosis is a common and significant valve condition requiring bioprosthetic heart valves with transcatheter aortic valve replacement (TAVR) being strongly recommended for high-risk patients or patients over 75 years. This meta-analysis aimed to pool existing data on postprocedural clinical as well as echocardiographic outcomes comparing valve-in-valve (ViV)-TAVR to redo-surgical aortic valve replacement to assess the short-term and medium-term outcomes for both treatment methods. A systematic literature search on Cochrane Central, Scopus, and Medline (PubMed interface) electronic databases from inception to August 2023. We used odds ratios (OR) for dichotomous outcomes and mean differences (MD) for continuous outcomes. Twenty-four studies (25,216 patients) were pooled with a mean follow-up of 16.4 months. The analysis revealed that ViV-TAVR group showed a significant reduction in 30-day mortality (OR 0.50, 95% confidence interval [CI] 0.43 to 0.58, p <0.00001), new-onset atrial fibrillation (OR 0.34, 95% CI 0.17 to 0.67, p = 0.002), major bleeding event (OR 0.28, 95% CI 0.17 to 0.45, p <0.00001) and lower rate of device success (OR 0.25, 95% CI 0.12 to 0.53, p = 0.0003). There were no significant differences between either group when assessing 1-year mortality, stroke, myocardial infarction, postoperative left ventricular ejection fraction, and effective orifice area. ViV-TAVR cohort showed a significantly increased incidence of paravalvular leaks, aortic regurgitation, and increased mean aortic valve gradient. ViV-TAVR is a viable short-term option for elderly patients with high co-morbidities and operative risks, reducing perioperative complications and improving 30-day mortality with no significant cardiovascular adverse events. However, both treatment methods present similar results on short-term to medium-term complications assessment.

The efficacy of non-pharmacological and non-pacing therapies in preventing vasovagal syncope: Tilt training, physical counter pressure maneuvers, and yoga - A systematic review and meta-analysis.

BACKGROUND: Vasovagal syncope (VVS) is a prevalent condition characterized by a sudden drop in blood pressure and heart rate, leading to a brief loss of consciousness and postural control. Recurrent episodes of VVS significantly impact the quality of life and are a common reason for emergency department visits. Non-pharmacological interventions, such as tilt training, physical counter pressure maneuvers, and yoga, have been proposed as potential treatments for VVS. However, their efficacy in preventing VVS remains uncertain. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Web of Science, and Embase were searched up to March 2023 for randomized controlled trials comparing non-pharmacological interventions with control in preventing VVS recurrence. The primary outcome was the recurrence rate of VVS episodes. RESULTS: A total of 1130 participants from 18 studies were included in the meta-analysis. The overall mean effect size for non-pharmacological interventions versus control was 0.245 (95 % CI: 0.128-0.471, p-value <0.001). Subgroup analysis showed that yoga had the largest effect size (odds ratio 0.068, 95 % CI: 0.018-0.250), while tilt training had the lowest effect size (odds ratio 0.402, 95 % CI: 0.171-0.946) compared to control. Physical counter pressure maneuvers demonstrated an odds ratio of 0.294 (95 % CI: 0.165-0.524) compared to control. CONCLUSION: Non-pharmacological interventions show promise in preventing recurrent VVS episodes. Yoga, physical counter pressure maneuvers, and tilt training can be considered as viable treatment options. Further research, including randomized studies comparing pharmacological and non-pharmacological approaches, is needed to evaluate the safety and efficacy of these interventions for VVS treatment.

First-line Systemic Treatment Options for Metastatic Castration-Sensitive Prostate Cancer: A Living Systematic Review and Network Meta-analysis.

Importance: The effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive prostate cancer (mCSPC) is unknown. Objective: To assess the comparative effectiveness of contemporary systemic treatment options for patients with mCSPC across clinically relevant subgroups. Data Sources: For this systematic review and meta-analysis, Ovid MEDLINE and Embase were searched from each database's inception (MEDLINE, 1946; Embase, 1974) through June 16, 2021. Subsequently, a "living" auto search was created with weekly updates to identify new evidence as it became available. Study Selection: Phase 3 randomized clinical trials (RCTs) assessing first-line treatment options for mCSPC. Data Extraction and Synthesis: Two independent reviewers extracted data from eligible RCTs. The comparative effectiveness of different treatment options was assessed with a fixed-effect network meta-analysis. Data were analyzed on July 10, 2022. Main Outcomes and Measures: Outcomes of interest included overall survival (OS), progression-free survival (PFS), grade 3 or higher adverse events, and health-related quality of life. Results: This report included 10 RCTs with 11 043 patients and 9 unique treatment groups. Median ages of the included population ranged from 63 to 70 years. Current evidence for the overall population suggests that the darolutamide (DARO) triplet (DARO + docetaxel [D] + androgen deprivation therapy [ADT]; hazard ratio [HR], 0.68; 95% CI, 0.57-0.81), as well as the abiraterone (AAP) triplet (AAP + D + ADT; HR, 0.75; 95% CI, 0.59-0.95), are associated with improved OS compared with D doublet (D + ADT) but not compared with API doublets. Among patients with high-volume disease, AAP + D + ADT may improve OS compared with D + ADT (HR, 0.72; 95% CI, 0.55-0.95) but not compared with AAP + ADT, enzalutamide (E) + ADT, and apalutamide (APA) + ADT. For patients with low-volume disease, AAP + D + ADT may not improve OS compared with APA + ADT, AAP + ADT, E + ADT, and D + ADT. Conclusions and Relevance: The potential benefit observed with triplet therapy must be interpreted with careful accounting for the volume of disease and the choice of doublet comparisons used in the clinical trials. These findings suggest an equipoise to how triplet regimens compare with API doublet combinations and provide direction for future clinical trials.

The Role of Systemic Therapy in Resectable Colorectal Liver Metastases: Systematic Review and Network Meta-Analysis.

BACKGROUND: Despite multiple randomized trials, the role of perioperative chemotherapy in colorectal cancer liver metastasis (CRLM) is still under debate. In this systematic review and network meta-analysis (NMA), we aim to evaluate the efficacy of perioperative systemic therapies for patients with CRLM. METHODS: We searched various databases for abstracts and full-text articles published from database inception through May 2021.We included randomized controlled trials (RCTs) comparing the addition of perioperative (post, pre, or both) systemic therapies to surgery alone in patients with CRLM. The outcomes were compared according to the chemotherapy regimen using a random effects model. Outcomes of interest included disease-free survival (DFS) and overall survival (OS). RESULTS: Seven RCTs with a total of 1504 patients with CRLM were included. Six studies included post-operative treatment and one evaluated perioperative (pre- and postoperative) therapy. Fluoropyrimidine-based chemotherapy was the most used systemic therapy. NMA showed benefit of adding perioperative therapy to surgery in terms of DFS (HR 0.73, 95% CI 0.63 to 0.84). However, these findings did not translate into a statistically significant OS benefit (HR 0.88, 95% CI 0.74 to 1.05). NMA did not show any advantage of one regimen over another including oxaliplatin or irinotecan. CONCLUSIONS: This systematic review and NMA of 7 RCTs found that the addition of perioperative systemic treatment for resectable CRLM could improve disease-free survival but not overall survival. Based on the findings, addition of perioperative treatment in resectable CRLM should be individualized weighing the risks and benefits.

Quantifying absolute benefit for adjuvant treatment options in renal cell carcinoma: A living interactive systematic review and network meta-analysis.

OBJECTIVE: To assess comparative effectiveness of adjuvant therapies for renal cell carcinoma and quantify the absolute benefit of adjuvant treatments by clinicopathological risk groups. METHODS: This 'living' review was conducted using Living Interactive Evidence (LIvE) synthesis framework. RESULTS: The 'living' results are available on an interactive website. This network meta-analysis, including six RCTs with 7525 participants, showed that pembrolizumab (rank 1) significantly improved disease-free survival and overall survival compared with sunitinib but not when compared to pazopanib, and axitinib. The risk of treatment-related grade 3 or higher adverse events was increased with pembrolizumab as compared to placebo and axitinib but not when compared to sunitinib. The absolute benefit of adjuvant pembrolizumab increases substantially with larger tumor size, nodal positivity and higher Leibovich scores. CONCLUSION: Current evidence suggests that pembrolizumab delays disease progression compared to sunitinib. A risk-adapted strategy should be used in patients undergoing consideration for treatment with adjuvant pembrolizumab.

Impact of autologous transplantation on survival in patients with newly diagnosed multiple myeloma who have high-risk cytogenetics: A meta-analysis of randomized controlled trials.

BACKGROUND: Despite routine evaluation of cytogenetics in myeloma, little is known regarding the impact of high-dose therapy (HDT) consolidation on overall survival (OS) or progression-free survival (PFS) in patients who have high-risk cytogenetics. The authors performed a meta-analysis of randomized controlled trials (RCTs) to assess the heterogeneity of HDT efficacy according to cytogenetic risk. METHODS: All RCTs in patients who had newly diagnosed myeloma from 2000 to 2021 that compared upfront HDT versus standard-dose therapy (SDT) consolidation were included. The primary objective was to assess the difference in HDT efficacy between standard-risk and high-risk cytogenetics in terms of the OS or PFS log(hazard ratio) (HR). The pooled OS and PFS HR was calculated according to cytogenetic-risk subgroup using a random-effects model, and heterogeneity (I2 ) (the percentage of total observed variability explained by between-study differences) was assessed using an interaction test. RESULTS: After screening 3307 citations, 6 RCTs were included for PFS analysis, and 4 were included for OS analysis. The median follow-up ranged from 3.1 to 7.8 years. The pooled OS HR for HDT versus SDT consolidation in patients with standard-risk and high-risk cytogenetics was 0.90 (95% confidence interval [CI], 0.70-1.17; I2 = 0%) and 0.66 (95% CI, 0.45-0.97; I2 = 0%), respectively. The difference in HDT efficacy in terms of OS between standard-risk and high-risk patients was statistically significant in favor of the high-risk group (P for interaction = .03). The pooled PFS HR for HDT versus SDT was 0.65 (95% CI 0.56-0.76; I2 = 0%) versus 0.52 (95% CI, 0.33-0.83; I2 = 55%), respectively. The difference in HDT efficacy in terms of PFS between standard-risk and high-risk patients was not significant (P for interaction = .25). CONCLUSIONS: The magnitude of OS benefit with upfront HDT is cytogenetics-dependent. Patients with high-risk cytogenetics should preferably receive upfront rather than delayed HDT consolidation. LAY SUMMARY: Upfront autologous stem cell transplantation improves overall survival in patients with newly diagnosed myeloma harboring high-risk cytogenetics.

Disparities in Representation of Women, Older Adults, and Racial/Ethnic Minorities in Immune Checkpoint Inhibitor Trials.

PURPOSE: We aim to describe reporting and representation of minority patient populations in immune checkpoint inhibitor (ICI) clinical trials and assess predictors of enrollment disparity. METHODS: Trial-level data were acquired from eligible phase II and III trials. Population-based estimates were acquired from the SEER 18 and Global Burden of Disease incidence databases. Trials reporting race, age, and sex were summarized using descriptive statistics. Enrollment-incidence ratio (EIR) was used to assess representation of subgroups. Average annual percentage change (AAPC) in EIR was calculated using Joinpoint Regression Analysis. Trial-level characteristics associated with EIR were assessed using multivariable linear regression. RESULTS: A total of 107 trials with 48,095 patients were identified. Participation of Black, White, Asian, Native American, Pacific Islander, and Hispanic participants was reported in 65 (61%), 77 (72%), 68 (64%), 40 (37%,) and 24 trials (22%), respectively. Subgroup analyses of clinical outcomes by race, age, and sex were reported in 17 (22%), 62 (78%), and 57 (57%) trials, respectively. Women (trial proportion [TP]: 32%; EIR: 0.90 [95% confidence interval [CI]: 0.84-0.96]), patients aged ≥65 years (TP: 42%; EIR: 0.78 [95% CI: 0.72-0.84]), Black participants (TP: 1.9%; EIR: 0.17 [95% CI: 0.13-0.22]) and Hispanics (TP: 5.9%; EIR: 0.67 [95% CI: 0.53-0.82]) were underrepresented. Representation of Black patients decreased significantly from 2009 to 2020 (AAPC: -23.13). Black participants were significantly underrepresented in phase III trials (P < .001). CONCLUSION: The reporting of participation by racial or ethnic subgroup categories is inadequate. Women, older adults, as well as Black and Hispanic participants are significantly underrepresented in ICI clinical trials.

Adjuvant Tyrosine Kinase Inhibitors in Renal Cell Carcinoma: A Concluded Living Systematic Review and Meta-Analysis.

PURPOSE: Multiple large clinical trials have investigated adjuvant tyrosine kinase inhibitors (TKIs) to reduce the risk of cancer recurrence and progression to metastasis in high-risk renal cell carcinoma. We sought to maintain living and interactive evidence on this topic, until a high level of certainty is reached for key clinical outcomes such that further updates become unnecessary and unlikely to change clinical practice. METHODS: We created a living interactive evidence synthesis platform to maintain a continuously updated meta-analysis on TKI monotherapy in adjuvant renal cell carcinoma. We implemented an automated search strategy with weekly updates to identify randomized phase 2 and 3 clinical trials. Study selection, appraisal, and data extraction were done in duplicate. Cumulative meta-analysis was performed using Analyzer Module in Living Interactive Evidence platform. For each outcome (overall survival [OS], disease-free survival [DFS], and all-cause and treatment-related adverse events), we assessed certainty of evidence using GRADE approach and conducted trial sequential analysis. RESULTS: This final update includes five randomized trials including recently updated data from PROTECT trial. Meta-analysis shows that adjuvant TKI monotherapy offers no benefit in OS (hazard ratio, 1.01; 95% CI, 0.91 to 1.12, high certainty) or DFS (hazard ratio, 0.92; 95% CI, 0.86 to 1.00, high certainty) and significantly increases adverse event risk. Lack of benefit was consistent across subgroups including highest-risk patients (test for subgroup differences: P = .32). Optimal information size criteria were met, and there was high certainty of evidence for lack of DFS and OS benefit for adjuvant TKIs. CONCLUSION: There is no guidance on when to stop maintaining a living review. In this example, we used trial sequential analysis and high certainty of evidence (future clinical trials unlikely to change current conclusions) as a benchmark to conclude a living review in view of convincing evidence.

A Living, Interactive Systematic Review and Network Meta-analysis of First-line Treatment of Metastatic Renal Cell Carcinoma.

CONTEXT: Identifying the most effective first-line treatment for metastatic renal cell carcinoma (mRCC) is challenging as rapidly evolving data quickly outdate the existing body of evidence, and current approaches to presenting the evidence in user-friendly formats are fraught with limitations. OBJECTIVE: To maintain living evidence for contemporary first-line treatment for previously untreated mRCC. EVIDENCE ACQUISITION: We have created a living, interactive systematic review (LISR) and network meta-analysis for first-line treatment of mRCC using data from randomized controlled trials comparing contemporary treatment options with single-agent tyrosine kinase inhibitors. We applied an advanced programming and artificial intelligence-assisted framework for evidence synthesis to create a living search strategy, facilitate screening and data extraction using a graphical user interface, automate the frequentist network meta-analysis, and display results in an interactive manner. EVIDENCE SYNTHESIS: As of October 22, 2020, the LISR includes data from 14 clinical trials. Baseline characteristics are summarized in an interactive table. The cabozantinib + nivolumab combination (CaboNivo) is ranked the highest for the overall response rate, progression-free survival, and overall survival, whereas ipilimumab + nivolumab (NivoIpi) is ranked the highest for achieving a complete response (CR). NivoIpi, and atezolizumab + bevacizumab (AteBev) were ranked highest (lowest toxicity) and CaboNivo ranked lowest for treatment-related adverse events (AEs). Network meta-analysis results are summarized as interactive tables and plots, GRADE summary-of-findings tables, and evidence maps. CONCLUSIONS: This innovative living and interactive review provides the best current evidence on the comparative effectiveness of multiple treatment options for patients with untreated mRCC. Trial-level comparisons suggest that CaboNivo is likely to cause more AEs but is ranked best for all efficacy outcomes, except NivoIpi offers the best chance of CR. Pembrolizumab + axitinib and NivoIpi are acceptable alternatives, except NivoIpi may not be preferred for patients with favorable risk. Although network meta-analysis provides rankings with statistical adjustments, there are inherent biases in cross-trial comparisons with sparse direct evidence that does not replace randomized comparisons. PATIENT SUMMARY: It is challenging to decide the best option among the several treatment combinations of immunotherapy and targeted treatments for newly diagnosed metastatic kidney cancer. We have created interactive evidence summaries of multiple treatment options that present the benefits and harms and evidence certainty for patient-important outcomes. This evidence is updated as soon as new studies are published.

Are patients on oral anticoagulation therapy aware of its effects? A cross-sectional study from Karachi, Pakistan.

OBJECTIVE: Oral anticoagulants are one of the most frequently used medications. However, these drugs have a range of side effects including potential life-threatening complications. Little is known regarding the awareness of its side effect profile amongst the patients in Pakistan. Therefore, the aim of this study was to assess the knowledge of oral anticoagulant therapy and its side effects among its users. RESULTS: The mean age was 48.9 ± 15.2 years. Median scores of the participants for knowledge regarding oral anticoagulants and warfarin were 48.7 (8.3-91.7) and 10.3 (0.0-70.0) respectively. Of 207 patients, most notably, 65.7% did not know what side effects to be wary of or how to reduce their occurrence; and most patients were unaware of the interaction between oral anticoagulant drugs and over-the-counter substances such as aspirin, herbal medicines and alcohol. Knowledge of international normalised ratio (INR) was extremely poor with more than 75% of the population not being aware of the target INR range during warfarin therapy. Higher level of education was significantly associated with better knowledge scores. Overall, knowledge of oral anticoagulant therapy and INR monitoring is extremely poor among oral anticoagulant users.

Knowledge and Attitude Regarding Telemedicine Among Doctors in Karachi.

Background Telemedicine is an affordable use of information and communication technology (ICT) to enable long-distance patient care and health care services. While the developed world continues to take advantage of this technology, its concept remains new to Pakistan. This study aims to assess the knowledge and perceptions regarding telemedicine among health care professionals in Karachi, Pakistan. Methods  This cross-sectional study was carried out among doctors employed in the public health sector in Karachi from June 2018 to August 2018. Data were collected using a self-designed well-structured questionnaire using a five-point Likert scale, built after an extensive literature review. Statistical analysis was carried out using SPSS version 22. Categorical data were reported as frequencies and percentages. Results A total of 224 doctors, working in the Department of Internal Medicine (27.6%), Pediatrics (9.8%), Cardiology (6.6%), Gynecology (5.35%), Neurology (5.8%), and other specialties (44.6%), participated in the study. A total of 80.7 % of the doctors were aware of the definition of telemedicine. A total of 28.1% of them believed telemedicine to be effective in providing faster medical care while 23.2% thought of it as a means of reducing the white coat syndrome. A total of 42.9% believed that telemedicine disrupts the doctor-patient relationship and causes a breach of patient privacy. A total of 34.8% of the doctors favored the idea of introducing national standards for practicing telemedicine while 33.5% of doctors also agreed that providing a legal explanation of telemedicine to patients was of paramount importance. Poverty and lack of education (90.6%) was thought to be the biggest barrier to the practice of telemedicine in the developing world. Conclusions The knowledge regarding telemedicine among doctors in Karachi was found to be average. However, the perceptions about and attitude towards the introduction and implementation of this new technology were welcomed by the majority of participants with an emphasis on increasing awareness. Conferences and workshops are needed to increase knowledge about telemedicine in Pakistan.

Gender Differences in Faculty Rank and Leadership Positions Among Hematologists and Oncologists in the United States.

PURPOSE: Gender disparity persists in academic medicine. Female faculty are underrepresented in leadership positions and have lower research output. We studied gender differences in faculty rank and departmental leadership and contributing factors among academic hematologists and oncologists in the United States. METHODS: For clinical faculty at 146 hematology or oncology fellowship programs listed in the Fellowship and Residency Electronic Interactive Database, we collected data on demographics, academic rank, and research output using the Doximity and Scopus databases. We compared unadjusted characteristics of men and women by using 2-sided t tests and χ2 tests where appropriate. To predict probability of full professorship or leadership position among men versus women, we performed multivariable logistic regression analysis adjusted for clinical experience in years, number of publications, h-index, clinical trial investigator status, National Institutes of Health funding, and workplace ranking (top 20 v not). RESULTS: Two thousand one hundred sixty academic hematologists and oncologists were included. Women composed 21.9% (n = 142) of full professors, 35.7% (n = 169) of associate professors, and 45.4% (n = 415) of assistant professors. Thirty percent (n = 70) of departmental leaders were women. Female faculty, compared with male faculty, had a lower mean h-index (12.1 v 20.9, respectively; P < .001) and fewer years of professional experience since fellowship (10 v 16 years, respectively; P < .001). After adjusting for duration of clinical experience, academic productivity, and workplace ranking, the odds of obtaining professorship (odds ratio [OR], 1.05; 95% CI, 0.71 to 1.57; P = .85) or divisional leadership (OR, 0.57; 95% CI, 0.20 to 1.58; P = .28) for female physicians were not different compared with male physicians. CONCLUSION: Gender disparity exists in senior ranks of academic hematology and oncology; however, gender is not a significant predictor in achieving professorship or department leadership position.

Solitary Splenic Tuberculosis in an Immunocompetent Child: A Case Report.

Tuberculosis (TB) is a lethal infectious disease that still remains a major threat in developing countries. Solitary splenic tuberculosis is a rare entity and there have been very few cases of it reported in literature. It is mostly encountered in patients who have an immunocompromised state. It may occur with a myriad of non-specific presentations, making it complex to diagnose. Here, we report a case of an eight-year-old female, immunocompetent, who had complaints of fever, abdominal pain and chronic diarrhea. Laboratory data failed to provide any information about the final diagnosis. On physical examination, splenomegaly was present. Imaging studies were conducted with an abdominal ultrasound showcasing mild ascites, splenomegaly, with a homogeneous echo pattern and no focal mass. Computed tomography (CT) of the abdomen showed two hypodense areas in the subcapsular region of the spleen and extending into the capsule, suggestive of a tuberculous abscess with mesenteric lymphadenopathy. The diagnosis was further corroborated when the patient showed remarkable improvement on anti-tuberculous therapy. This is a very uncommon phenomenon, especially in an immunocompetent patient and hence, it is very important to keep this on the list of differentials especially in an area where TB is endemic.

Gender differences amongst board members of endocrinology and diabetes societies.

PURPOSE: Although women's status has shown marked improvement over the years in many areas, women still face a gender bias, especially in the workforce. Despite the best efforts of organizations to promote diversity and equality, women still dominate the lower-paying administrative ranks while men continue to dominate at the executive level. The present study examines gender disparity in the leadership positions in the national and international endocrinology and diabetes societies across the globe. METHODS: We first composed a list of Diabetes and Endocrinology societies from online databases, including the International Diabetes Federation, European Society of Endocrinology, and other similar online directories. The Scopus database author search was used to find the total number of publications, publication range (in years), h-indices, number of citations, and years of active research of each member. RESULTS: Our study included 524 board members of whom 31.3% (164/524) were women. The institutional academic rank of 310 of the total board members was found. The proportion of women in higher-faculty ranks (Assistant Professor, Associate Professors, and Professors) is much lower than males. Female endocrinologists also have fewer publications, citations, and years of active research. CONCLUSIONS: Endocrinology is becoming a female-predominant subspecialty of internal medicine. As women are becoming a more significant portion of the endocrinology workforce, it is imperative to study and mitigate gender differences and disparities to optimize the endocrinology workforce.

Disparity in Leadership in Neurosurgical Societies: A Global Breakdown.

OBJECTIVE: Gender disparity in academic and organizational settings has been the topic of numerous studies and they have tried to extract its causes using H-index as the prime metric. The primary objective of our study was to assess gender disparity in leadership positions in neurosurgical societies worldwide. A second objective was to evaluate scholarly output among neurosurgeons in neurosurgical societies worldwide, utilizing H-index as a predominant metric. METHODS: The World Federation of Neurosurgeons database was used to gather details on the neurosurgical societies present worldwide. Online data present for leadership positions were extracted from each of the respective societies. Neurosurgeons holding leadership positions were arranged according to their academic and hierarchical ranks. The Scopus database was used to calculate H-index along with other bibliometric variables. RESULTS: H-index was statistically significant between both genders, with male neurosurgeons having significantly higher H-index than female neurosurgeons. A positive correlation was also found between H-index and academic ranks of neurosurgeons. However, no statistical significance was found between H-index and executive committee positions. Female neurosurgeons held 29% executive committee positions globally. CONCLUSIONS: A paucity of female neurosurgeons was seen in leadership positions in neurosurgical societies worldwide. Significant disparity present in research productivity between genders is a highlighted statistic further discussed in this study, considering variables such as H-index among others. The increase in female neurosurgeons to neurosurgical organizational echelons can be achieved by enhancing institutionalized support, setting up networking platforms, and identifying mentorship opportunities for prospective leaders.

Philadelphia chromosome-like acute lymphoblastic leukemia: A review of the genetic basis, clinical features, and therapeutic options.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently identified high-risk subtype of B-lineage ALL (B-ALL), characterized by a gene expression profile similar to that of Philadelphia-positive (Ph+) ALL, but without the hallmark BCR-ABL1 oncoprotein. Ph-like ALL represents approximately 15% of childhood ALL and its frequency rises with age, peaking among adolescents, and young adults with B-ALL. This subtype is associated with adverse clinical features, persistence of minimal residual disease, and a poor prognosis despite modern chemotherapy regimens. While Ph-like ALL lacks the BCR-ABL1 fusion, it is characterized by a diverse spectrum of kinase fusions and cytokine receptor gene rearrangements that may be similarly amenable to molecularly targeted therapies. While survival rates for childhood ALL have drastically improved with intensive conventional chemotherapy, Ph-like ALL represents a novel paradigm of precision medicine in ALL. This review aims to provide a comprehensive review of the clinical picture and genetic basis of Ph-like ALL and to illustrate how these findings can translate into tailored targeted therapies with the hopes of improving the outcomes of Ph-like ALL patients.

An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL).

Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis, representing only about 2-5% of acute leukemia cases. The blast cells of MPAL express multilineage immunophenotypic markers and may have a shared B/T/myeloid phenotype. Due to historical ambiguity in the diagnosis of MPAL, the genetics and clinical features of this disease remain poorly characterized. Based on the 2008 and 2016 World Health Organization classifications, myeloid lineage is best determined by presence of myeloperoxidase, while B and T lymphoid lineages are demonstrated by CD19 and cytoplasmic CD3 expression. MPAL typically carries a worse prognosis than either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). Given the rarity of MPAL, there is a lack of prospective trial data to guide therapy; treatment generally relies on ALL-like regimens followed by consolidation chemotherapy or hematopoietic stem cell transplant (HSCT). Here, we review the updated classification, biology, clinical features, and treatment approach to MPAL.