Muhammad Ali Tariq

Background: Outcomes in chronic myeloid leukemia (CML) remain heterogeneous despite effective BCR::ABL1 tyrosine kinase inhibitors (TKIs). Somatic mutations in epigenetic regulators, particularly additional sex combs like 1 (ASXL1), have been implicated in adverse prognosis, but their clinical impact in CML has not been systematically defined. Methods: A systematic review was conducted using CINAHL, EMBASE, MEDLINE Ultimate, and PubMed from inception through August 2025. A total of 1,339 records were identified; after duplicate removal and screening, 11 studies met inclusion criteria and were included in qualitative synthesis and meta-analysis. Eligible studies included adult and pediatric patients with chronic and advanced phase (accelerated or blast) CML with ASXL1 mutation status assessed using validated molecular methods. Outcomes included molecular response, cytogenetic response, survival, and treatment resistance. Random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CI). Statistical heterogeneity was assessed using the I² statistic. Results: Across included studies, ASXL1 mutations were detected in approximately 16% of patients. At 12 months, ASXL1-mutated patients had significantly lower odds of achieving major molecular response (MMR) compared with ASXL1–wildtype patients (OR 0.29; 95% CI 0.16–0.51; p< 0.0001; I²=30%). No statistically significant difference was observed in complete cytogenetic response (CCyR) (OR 0.30; 95% CI 0.02–5.31; p=0.41; I²=68%). Compared with patients harbouring other non-ASXL1 somatic mutations, ASXL1 mutation was not associated with a significant difference in MMR (OR 0.49; 95% CI 0.23–1.05; p=0.067; I²=0%). Conclusions: ASXL1 mutations are associated with inferior molecular response to TKI therapy in CML, supporting their role as an adverse prognostic biomarker. These findings highlight the potential value of incorporating myeloid mutation profiling into future CML risk-stratification strategies.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystem involvement. It is multifactorial and involves epigenetic, genetic, ecological, and environmental factors. Primarily it leads to activation of both innate and adaptive immunity, which consequently leads to autoreactive B cell activation by T cells and leads to immune complexes deposition in tissues leading to an autoimmune cascade that may be limited to the single organ or can cause a widespread systemic involvement. SLE is heterogeneous in presentation, with a broad spectrum of clinical manifestations ranging from clinically mild self-resolving symptoms to severe life-threatening organ involvement. Clinical and serological heterogeneity are critical features in SLE, posing a significant challenge in its diagnosis. Antinuclear antibodies (ANA) are the telltale serological marker in more than 95% of SLE patients. The improved set of European Alliance of Associations for Rheumatology (EULAR) classification enabled accurate diagnosis of SLE. The treatment focuses on remission, preventing organ damage, and improving the overall quality of life.

Waardenburg syndrome (WS) is a rare genetic disorder. It is caused by multiple mutations affecting the melanocytes, leading to a multitude of skin, hair, and eye symptoms. It is an autosomal dominant disease with four subtypes, each presenting with varying degrees of sensorineural hearing loss along with a constellation of other symptoms. Hirschsprung disease is unique to Waardenburg-Shah syndrome subtype 4 and is not associated with any other subtype. We present a case of this subtype 4 that presented with a bilateral sensorineural hearing loss, mutism, delayed milestones, white forelock, Hirschsprung disease, and bilateral blue homochromatic irises, a finding which is not typical for this subtype. This is the first case of WS with homochromatic irises and the fourth case to be reported from Pakistan.

The prolonged use of levodopa for treating Parkinson’s disease is associated with motor and nonmotor complications. These include wearing-off, delayed-on, partial-on, no-on, and on-off phenomena. In the wearing-off effect, symptoms return before a patient's next scheduled dose of levodopa. Patients may present with motor, sensory, or autonomic fluctuations. In this report, we present a female patient experiencing numbness of lips and slurred speech as a symptom of wearing-off effect. The major differential for sudden numbness of lips and slurred speech includes transient ischemic attacks. Therefore, it is imperative to identify the cause of these episodes so that appropriate treatment can be initiated. Our patient underwent extensive cardiac and neurological investigations, the findings of which were unremarkable. Her symptoms were likely due to levodopa wearing-off. Her condition improved on changing her levodopa to a sustained release form with more frequent dosing along with the addition of ropinirole to her treatment regimen.