Muhammad Abdul Rehman

Background: BRAF V600E–mutant metastatic colorectal cancer (mCRC) represents an aggressive molecular subtype associated with poor prognosis and limited response to conventional chemotherapy. Although multiple targeted strategies, including anti-vascular endothelial growth factor ( VEGF ), anti-epidermal growth factor receptor ( EGFR ), and BRAF -directed therapies, are used in clinical practice, their comparative effectiveness remains uncertain. We performed a reconstructed individual patient–data (IPD) meta-analysis of randomized controlled trials (RCTs) to evaluate survival outcomes across targeted therapeutic classes in BRAF -mutant mCRC. Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane databases was conducted through July 2025 to identify RCTs reporting survival outcomes for BRAF -mutant mCRC. Kaplan–Meier curves were digitized and IPD reconstructed using established methods. A one-stage meta-analysis using Cox proportional hazards models was performed to estimate pooled overall survival (OS) and progression-free survival (PFS). Models were adjusted for study-level covariates and clustering, with Bonferroni correction applied for multiple comparisons. Results: Eighteen RCTs comprising 11,931 participants were included. Pooled median OS was 22.3 months for BRAF -directed regimens, 17.1 months for VEGF -targeted therapy, and 10.1 months for EGFR-directed therapy across studies evaluating first-line therapy. Across first-line studies, BRAF inhibitor directed regimen was associated with significantly improved OS compared with EGFR inhibition (HR 0.43, 95% CI 0.31–0.60; P < 0.001) and improved PFS (HR 0.47, 95% CI 0.42–0.53; P < 0.001). VEGF inhibition also demonstrated superior OS compared with EGFR inhibition (HR 0.56, 95% CI 0.38–0.81; p < 0.001). EGFR -directed regimen consistently demonstrated the poorest survival outcomes across analyses. Discussion: In this reconstructed IPD meta-analysis, BRAF -directed therapies were associated with the most favourable survival outcomes, whereas EGFR directed regimen demonstrated limited clinical benefit in BRAF -mutant mCRC. These results highlight the importance of biologically aligned pathway-targeted therapy and provide comparative evidence to inform treatment selection in this aggressive molecular subtype.

Background: Oral anticoagulation (OAC) remains the cornerstone of stroke prevention in atrial fibrillation (AF) but is limited by bleeding risk. Left atrial appendage occlusion (LAAO) devices offer an alternative; however, recent randomized trials have reported inconsistent efficacy compared with OAC. Methods: We conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing LAAO with OAC through April 1, 2026, using MEDLINE, EMBASE, and Cochrane CENTRAL. Eligible studies enrolled adults (≥18 years) with AF randomized to LAAO or OAC. Primary and secondary outcomes were pooled as risk ratios (RR) with 95% confidence intervals (CIs). Individual patient‐level data (IPD) were reconstructed from published Kaplan–Meier curves for time‐to‐event sensitivity analyses. Results: Six RCTs ( n = 7,004; mean age 72 years; CHA ₂ DS ₂ ‑VASc 3.9; HAS‑BLED 1.7; mean follow‐up 38 months) were included. LAAO showed no significant difference in ischemic stroke (RR 1.20, 95% CI 0.82–1.76), major bleeding (RR 0.77, 95% CI 0.50–1.17), or all‐cause mortality (RR 0.96, 95% CI 0.82–1.13) compared with OAC. Hemorrhagic stroke risk was significantly lower with LAAO (RR 0.53, 95% CI 0.30–0.93). Reconstructed IPD demonstrated similar stroke and bleeding risks (HR 1.24 and 0.84, respectively) but lower all‐cause mortality with LAAO (HR 0.70, 95% CI 0.52–0.95). Conclusion: LAAO provides comparable ischemic stroke prevention and major bleeding outcomes to OAC and reduces hemorrhagic stroke risk. Reconstructed IPD analyses suggest a possible mortality benefit that warrants further investigation. Future studies using contemporary devices and post‐ablation populations are needed to refine patient selection and further characterize the comparative clinical outcomes of LAAO and OAC in AF patients.

Accurate tissue acquisition (TA) of solid pancreatic lesions is essential for guiding treatment with endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) being the preferred method. Among FNB designs, the three-pronged Franseen-tip needle demonstrates strong diagnostic performance, though direct head-to-head comparisons with other FNB designs remain limited. This meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420251123856). Eligible studies enrolled patients with solid pancreatic lesions who underwent EUS-guided FNB, directly compared the Franseen-tip with other FNB needles. Six databases were systematically searched through July 2025, and study selection, data extraction, and risk of bias assessment (QUADAS-2 tool) were performed independently by two reviewers. Pooled estimates were generated using random-effects and bivariate hierarchical models. Sixteen studies (2,010 Franseen vs. 2,811 comparator) were included. Bivariate analysis showed that sensitivity and specificity of the Franseen needle were comparable to newer-generation comparator needles (sensitivity 91.3% vs. 94.0%; specificity 99.99% vs. 99.15%), whereas older-generation needles demonstrated lower sensitivity (80.8%) and inferior discriminatory performance (Negative Likelihood Ratio [LR⁻] 0.19 vs. 0.09). Diagnostic accuracy was higher with the Franseen needle (RR 1.07, 95% CI 1.01-1.14; I² = 69%). Sample adequacy was similar overall (RR 1.04, 95% CI 0.95-1.14) but superior to older-generation needles (RR 1.19, 95% CI 1.02-1.41) and in lesions > 30 mm (RR 1.14, 95% CI 1.02-1.28, I² = 81.2%). The Franseen needle achieved nominally strong diagnostic performance (DOR 116.6), although small-study effects were observed. Primary procedural outcomes were comparable between Franseen and comparator needles, including technical success (RR 1.00, 95% CI 0.98-1.02) and histological core procurement (RR 1.04, 95% CI 0.92-1.17). The Franseen needle had fewer low-cellularity samples (RR 0.56, 95% CI 0.45-0.69) and lower specimen bloodiness (RR 0.48, 95% CI 0.25-0.90) but a slightly higher overall adverse event rate (RR 1.29, 95% CI 1.06-1.57). The Franseen needle provides superior diagnostic accuracy and sample adequacy compared to older-generation FNB needles with comparable performance to newer-generation designs. It reduces low-cellularity samples and specimen bloodiness, although adverse events are slightly increased, with other primary procedural outcomes remaining comparable. PROSPERO (Registration No. CRD420251123856).

Introduction Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) affects up to 9% of average-risk and 40% of high-risk patients. Rectal NSAIDs are guideline-recommended for PEP prophylaxis, yet direct evidence comparing different NSAIDs remains scarce. This study systematically evaluates head-to-head evidence to compare the efficacy of rectal diclofenac versus indomethacin in the prevention of PEP. Methodology This systematic review and meta-analysis adhered to the PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251107055). Eligible studies directly compared rectal diclofenac versus indomethacin for PEP prevention in adults undergoing ERCP. A comprehensive search of five databases was performed through July 2025. Pooled risk ratios with 95% CIs were calculated using fixed- or random-effects models based on heterogeneity, and certainty of evidence was assessed using the GRADE approach. Results Four studies (three RCTs, one observational; n = 2,917) compared rectal diclofenac (n = 1,275) and indomethacin (n = 1,642) for PEP prevention. Baseline characteristics were comparable, except for less frequent balloon dilatation with diclofenac (RR 0.78, 95% CI 0.68–0.89; p < 0.001). No significant differences were found for overall PEP (RR 1.17, 95% CI 0.92–1.49; I² = 0%), mild PEP (RR 1.24, 95% CI 0.94–1.63; I² = 0%), moderate PEP (RR 0.60, 95% CI 0.21–1.73; I² = 0%), severe PEP (RR 1.09, 95% CI 0.32–3.77; I² = 1%), or moderate-to-severe PEP (RR 0.97, 95% CI 0.46–2.05; I² = 0%). Secondary outcomes, including mortality and complications, were also similar, with low heterogeneity, indicating equivalent efficacy and safety. Conclusion Diclofenac and indomethacin demonstrate equivalent efficacy and safety, allowing cost and availability to inform the choice of PEP prophylaxis.

Background: Up to 80% of persons with Parkinson's disease (PwPD) have dysphagia. However, existing studies are based on small cohorts and the relationship between dysphagia and other motor and nonmotor symptoms (NMS) remains incompletely understood. Objectives: To evaluate the relationship between motor and NMS in PwPD with vs without dysphagia. Methods: Among 20,365 PwPD in the Michael J. Fox Foundation database who completed ≥2 NMS surveys, 12,678 (62%) reported dysphagia on ≥1 survey. We examined associations between dysphagia and: (1) self‐reported motor symptoms (UPDRS Part II), other NMS, quality of life (QoL), comorbidity score, depression, and daily activities at baseline; and (2) development of new NMS. Results: Compared to PwPD without dysphagia, those with dysphagia were more likely to have had PD for >5 years, more severe motor and NMS, higher comorbidity scores, and a greater impairment in daily activities ( P < 0.001). The prevalence of dysphagia increased with the severity of motor symptoms at the index survey ( P < 0.001). At baseline, all NMS were significantly associated with dysphagia. Compared to PwPD who did not have dysphagia, PwPD with dysphagia were at increased risk of developing every NMS, even after adjusting for ages at PD diagnosis and index survey, sex, cognitive impairment, UPDRS, NMS and comorbidity scores. For most NMS, the risk of progression was greater in those with cognitive impairment or elevated NMS scores. Conclusions: Dysphagia in PwPD is associated with more severe motor and non‐motor symptoms, reduced QoL, and an increased risk of future NMS.

Objectives: Barriers to breast cancer (BCa)-related care contribute majorly to a high mortality among Pakistani women. However, our understanding of these barriers is limited to studies that are limited geographically and by their small sample sizes. The objective of this study was to summarise all evidence and provide a comprehensive, one-stop manuscript which could assist interventionists who seek to address these barriers. Design: Systematic review Data sources: We searched PubMed, Embase, Scopus and Google Scholar and performed a citation search to search for eligible studies published since inception to 24 November 2024. Eligibility criteria: Observational studies that evaluated barriers to BCa-related care among Pakistani females were eligible. Data extraction and synthesis: We used the National Institutes of Health quality assessment tool to assess the risk of bias. Data were extracted into a template, classified into themes using inductive reasoning and analysed descriptively. Results: We found 37 studies which were eligible. In these, we identified eight barriers to BCa-related care for Pakistani women: lack of awareness, accessibility, affordability, fear, hesitancy, cultural traditions, commitments and physician error. Of these, physician error contributed the least, while lack of awareness, cultural traditions, fear and poor accessibility were most commonly reported. Importantly, these barriers to BCa-related care vary depending on the context (eg, population, geographical area, presence or absence of BCa). Most barriers influence others (eg, poverty leads to inaccessible healthcare), portraying a complex and multifaceted scenario. Conclusions: Barriers to BCa-related care can be grouped into eight broad themes. Their subthemes are diverse and interlinked. Policy-makers need to consider all barriers, as ignoring one can limit the effectiveness of their interventions. PROSPERO registration number: CRD42024612667

Background: Small studies suggest that constipation is a common symptom associated with a worse prognosis in patients with Parkinson's disease (PD). Objectives: The aim was to compare the association between constipation, motor, and other non‐motor symptoms (NMS) in PD patients at baseline and in future. Methods: Using the Fox Insight database, we compared baseline characteristics, risk of progressive motor symptoms, and incidence of NMS between PD patients with versus without constipation. Results: Of 20,352 participants, 16,611 (82%) reported infrequent bowel movements and/or excessive straining, 15,594 (77%) had incomplete evacuation, and 14,165 (70%) reported both symptoms. Patients with constipation were generally older, white, women, had PD >5 years, and had higher NMS and comorbidity scores ( P < 0.001). Constipation was significantly associated with worse motor symptoms and most NMS , especially fecal incontinence (odds ratio [ OR] = 1.65; 95% confidence interval [CI], 1.49–1.82), dysphagia ( OR = 1.20; 95% CI = 1.12–1.29), talking/moving during sleep ( OR = 1.39; 95% CI = 1.30–1.48), and urinary urgency ( OR = 1.23; 95% CI = 1.16–1.32). Constipation was associated with a small, but statistically significant increased risk of some progressive motor symptoms. At a mean median follow‐up of 2.8 years, constipation was associated with an increased risk of incident gastrointestinal, autonomic, neuropsychiatric, sleep‐related, sensory NMS , such as dysphagia (hazard ratio [ HR] = 1.43; 95% CI = 1.35–1.51), fecal incontinence ( HR = 1.87; 95% CI = 1.74–2.01), falls ( HR = 1.44; 95% CI = 1.35–1.52), hallucinations ( HR = 1.65; 95% CI = 1.52–1.79), cognitive impairment ( HR = 1.38; 95% CI = 1.30–1.47), and talking/moving during sleep ( HR = 1.65; 95% CI = 1.55–1.75). Conclusions: Constipation is a common symptom associated with severity of motor and other NMS and portends a worse prognosis in persons with PD.

The lack of a multidisciplinary approach to the management of cancer patients in most parts of Pakistan is a long-standing and major concern. To overcome this disparity, we started a student-run initiative to facilitate the establishment of multidisciplinary tumor boards (MTBs) in oncology, titled “Tumor Board Establishment Facilitation Forum (TEFF)”. The objectives of this study were to evaluate the clinical and academic impact of TEFF on cancer care for patients and student education, respectively. The formation of TEFF was based on the Theory of Change model. We conducted a needs assessment based on existing literature, physical evaluation of wards, and consultation with senior academic faculty members. The logic model was refined through multiple meetings between stakeholders. All engagements of TEFF described in this manuscript are limited to the Dow Medical College and its affiliated tertiary care hospital, Dr. Ruth K. M. Pfau Civil Hospital in Karachi, Pakistan. To gauge TEFF’s impact, we used administrative data generated between October 2021 to March 2024 to evaluate predefined outcomes (number of MTBs, cases, educational interventions, and research). The organizational structure comprised of 6 specialized departments: Communications, Operations, Media, Integrated Development, Research and Records, and Finance. We conducted 18 educational sessions for medical students about career guidance, research, cancer awareness; and 4 cancer awareness campaigns. TEFF facilitated the formation of 4 MTBs: breast, head and neck, gynecology, and pediatrics. Across these, 105 cases were discussed in 50 meetings. TEFF provided leadership opportunities, allowed familiarization with oncology, raised awareness of challenges associated with cancer care, allowed networking, and inculcated research-related skills and educational value through its MTBs. Medical students can contribute significantly to clinical care at the undergraduate level. For countries/regions struggling to provide multidisciplinary cancer care, TEFF’s model serves as a blueprint for a viable solution.