Pashupati Pokharel

Scrub typhus is an important cause of acute febrile illness in Nepal and can rarely present with meningoencephalitis and multiorgan involvement. We report a 32‐year‐old female farmer from rural Nepal who presented during the monsoon season with high‐grade fever, myalgia, vomiting, and an eschar following an unidentified forest bite. She developed meningismus, hypotension, mild acute respiratory distress syndrome, and transaminitis. Cerebrospinal fluid showed lymphocytic pleocytosis and elevated protein, while bacterial culture, acid‐fast staining, and GeneXpert were negative. Serum scrub typhus IgM was positive, whereas Brucella abortus IgM was borderline positive. CSF PCR for both pathogens was negative. Based on the characteristic eschar, clinical presentation, CSF findings, epidemiological exposure, and exclusion of alternative diagnoses, scrub typhus meningoencephalitis was considered the most likely diagnosis. She improved with doxycycline‐based therapy and achieved complete neurological recovery. This case highlights the challenges of diagnosing scrub typhus in resource‐limited settings despite negative PCR.

Background and Aims: Chronic Obstructive Pulmonary Disease (COPD) is associated with cognitive impairment, including memory loss, executive dysfunction and attention deficits all of which significantly affect quality of life. However, the prevalence and determinants of cognitive impairment among COPD patients in Nepal remain largely unexplored. Methods: This cross‐sectional study included a total of 203 COPD patients admitted to a tertiary hospital in Nepal between August 2022 and June 2023. Sociodemographic, clinical, and biochemical data were collected from the patients. Cognitive functions were assessed using the Nepali‐translated Rowland Universal Dementia Assessment Scale. Logistic regression analysis was conducted to identify factors associated with cognitive impairment. Results: The mean age of COPD patients was 68.4 ± 10.2 years, with most from the age group 65–75 years, and nearly 2/3rd (63.5%) were females. A majority (62.6%) lacked formal education, and 81.3% were smokers (current or former). Clinically, 45.3% of patients had grade III dyspnea, and 37.9% had pneumonia. Among the patients, 11.8% patients experienced more than five exacerbations in the past year, and 43.4% required more than one hospital admission during the previous year. Cognitive impairment was prevalent in majority of the patients, with 46.3% exhibiting mild cognitive impairment and 42.9% exhibiting dementia. Factors associated with cognitive impairment included increasing age of COPD patients (≥ 65 years) (OR 2.72; p = 0.003), having more than one COPD exacerbation in a year (OR 3.90; p = 0.002), years of living with COPD (≥ 10 years) (OR 0.47; p = 0.016), frequent COPD exacerbation related hospitalization (OR 0.29; p = 0.004), and lower blood PaCO ₂ levels (OR 0.26; p = 0.007). Conclusion: Nearly 90% of COPD patients in Nepal had some form of cognitive decline. Age, exacerbation frequency, and PaCO₂ levels were significant predictors. Routine cognitive screening and targeted interventions like integrated rehabilitation strategies, including pulmonary rehabilitation and oxygen therapy are essential to enhance patient outcomes and reduce disease burden in future.

Aims: This study entails an association between bronchial asthma and common single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) gene; rs2289278, rs3806933, rs2289276, and rs1837253. Methods: The databases of PubMed, Embase, Web of Science, and Google Scholar were searched for studies reporting TSLP polymorphisms and asthma from inception to January 2022. Hardy–Weinberg equilibriums (HWE) for each polymorphism of the control group were checked using the χ ² test. The association was estimated by means of odds ratio (OR) with 95% CI in both dominant and recessive modes of inheritance, respectively. Results: Altogether, 11 studies with 3121 asthma cases and 3041 healthy controls were added. Results from six studies showed that the SNP rs2289278 had a protective role in asthma development (OR=0.65, 95% CI: 0.44–0.97, P=0.04). Pooling of four studies showed that the SNP rs3806933 had higher odds of developing asthma (OR=1.32, 95% CI:1.14–1.54, P<0.01). However, the SNP rs2289276 and rs1837253 showed no significant association. From the subgroup analysis, SNPs rs2289278 and rs1837253 were protective against the development of asthma in Asia. However, SNP rs2289276 showed a risk association in Asia and in adults. Conclusion: This meta-analysis shows that the SNP rs2289278 has a protective effect on the development of asthma; whereas rs3806933 has a risk of asthma. Additionally, this study adds genomic-based support to the recent FDA approval of tezepelumab, an anti-TSLP agent.

Background: Sialidosis is a rare variety of lysosomal storage disease that results in intracellular accumulation of sialic acid containing compounds. The authors report the first case of type II sialidosis, juvenile subtype in a 30-month-old male child from Nepal. Case presentation: Progressive hearing loss with coarse facies, hepatomegaly, kyphoscoliosis, dysostosis multiplex were the major features in a 30-month-old child born to healthy non-consanguineous parents. With the suspicion of lysosomal storage disease, urinary oligosaccharides were tested and were positive. Whole-exome sequencing revealed a mutation in the neuraminidase gene (NEU1) and established the diagnosis of sialidosis. Clinical discussion: Sialidosis is a rare autosomal recessive type of lysosomal storage disease resulting due to mutation of the neuraminidase gene leading to intracellular accumulation of sialic acid compounds. Based on the presence of visual symptoms, sialidosis is classified into type I and II varieties. Our case is of type II juvenile sialidosis. Conclusion: Despite rare, sialidosis is a life-threatening, and disabling disease. Exploring targeted therapy is the utmost to treat this condition.

Introduction: Bardet–Biedl syndrome (BBS) is a rare autosomal recessive multisystem disorder characterized by retinal dystrophy, obesity, postaxial polydactyly, renal dysfunction, learning difficulties, and hypogonadism. In this case report, the authors present the clinical course and management of a patient with BBS who developed chronic kidney disease (CKD). Case presentation: An 18-year-old male presented to the emergency department with chief complaints of fever, cough, vomiting, and decreased urine output for 7 days. Parents complained that the child had a delay in development compared to other children of the same age group. On examination, the patient had tachypnea, periorbital and pedal edema, expiratory wheeze with bilateral basal crackles, polydactyly, central obesity, microtestes, and delayed developmental milestones. Ultrasonography revealed bilateral small kidneys with increased cortical echotexture and loss of corticomedullary differentiation. Based on clinical features, the patient was diagnosed with CKD in the background of BBS. Hemodialysis was initiated after the diagnosis. Discussion: The management of CKD in the background of BBS poses unique challenges due to the complex multisystem involvement of this genetic disorder. There should be early reorganization and management of this condition so that the patient can have a better quality of life. Moreover, in developing countries like Nepal, genetic testing and diagnosis should be made easily accessible for better patient outcome. Conclusion: Multidisciplinary approach involving nephrologists, ophthalmologists, endocrinologists, and geneticists is important to optimize the treatment and long-term management of Badet Biedel patients.

Dengue is a viral illness caused by dengue virus, a flavivirus transmitted by the bite of female Aedes aegypti and Aedes albopictus. In the year 2022, Nepal witnessed the largest ever dengue outbreak in the country. Dengue cases were reported from all seven provinces, affecting all 77 districts of the country. As of 31st December 2022, altogether 54 784 dengue cases have been identified, with Bagmati province reporting the highest. The country’s capital, Kathmandu, reported the highest burden of dengue cases (26%). The high degree of pre-monsoon rainfall because of climate change and mismanaged waste disposal system were the main cause of the 2022 dengue outbreak in Nepal. Furthermore, unplanned urbanization, Aedes vector expansion, open border policy with India, inefficient dengue surveillance system, and insufficient preventive efforts by the government are the causes of frequent dengue outbreaks. Awareness among the general public regarding vector control measures, improved surveillance of acute febrile illness, utilization of vector risk mapping techniques, and establishment of temperature-based early warning systems are utmost to halt future dengue outbreaks in Nepal.

Castleman's disease (CD) of the pancreas is a rare benign disease which can sometime resemble a pancreatic neuroendocrine tumor. We report a case of a 46-years-old lady with an incidental pancreatic lesion. Preoperative diagnosis was a neuroendocrine tumor of the pancreas, for which anterior Radical Antegrade Modular Pancreatosplenectomy surgery (RAMPs) was performed. The postoperative histopathology showed features consistent with hyaline vascular type Castleman's disease. She had an uneventful surgical procedure and no serious postoperative complications. Pancreatic Castleman's disease is usually difficult to diagnose and there is no specific clinical manifestation to distinguish it from a neuroendocrine tumor. Even with radiological imaging it is very difficult to distinguish Castleman's disease from neuroendocrine tumors, and the preoperative imaging diagnosis may not match with the postoperative histopathological diagnosis. Treatment of CD is surgical resection and has a good prognosis. Partial resection and radiation therapy or observation alone is an alternative to complete surgical resection. Castleman disease of the pancreas sometimes mimics neuroendocrine tumors of the pancreas. Clinicians should consider Castleman's disease of the pancreas as a differential diagnosis for neuroendocrine like lesions of the pancreas.

Background: Nepal is a low resource country with cardiovascular diseases being the number one cause of mortality. Despite hypertension being the single most important risk factor for cardiovascular diseases, non-adherence to anti-hypertensive medications has not been assessed systematically. So, this systematic review and meta-analysis aims to analyze the prevalence of non-adherence to anti-hypertensive medications in Nepal. Methodology: This systematic review and meta-analysis was piloted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Electronic databases of Embase, PubMed, Scopus, Web of Science, Cochrane Library, Cinhal Plus, and Google Scholar were searched from inception till 1 February 2023. The random-effects model with 95% confidence interval (CI) was used to calculate the non-adherence rate. Results: Altogether, 14 studies with a total of 3276 hypertensive patients were included in the meta-analysis. The pooled prevalence of non-adherence to anti-hypertensive medications was 49% (95% CI: 0.37–0.62, I ²=98.41%, PI ²=99.14%, PI ²=84.36%, PI ²=0.0%, P=0.46) compared to urban areas 42% (95% CI: 0.31–0.54, I ²=96.90%, P<0.001). The trend of non-adherence was increasing after 2020. Additionally, forgetfulness, carelessness, cost of medications, number of comorbidities, and using an alternate form of medication were common factors associated with non-adherence. Conclusions: This meta-analysis showed that half of the hypertensive population of Nepal are non-adherent to their anti-hypertensive medications, thereby posing a significant long-term cardiovascular consequence among Nepali population.

Background: Following the recent surge in monkeypox cases worldwide, vaccines have gained popularity due to their protective role against the disease in the absence of specific pharmacological therapies for the disease. This article explores the possible challenges associated with the treatment and prevention of monkeypox with special emphasis on cardiovascular concerns relating to vaccines, warranting further investigation and research. Methods: Multiple electronic databases from inception till October 2022 were searched to find articles reporting the cardiovascular adverse events associated with monkeypox immunization. Results: Smallpox vaccines ACAM2000, JYNNEOS, and modified vaccinia Ankara have been used for monkeypox. ACAM2000 has been reported to have major cardiovascular adverse events such as myocarditis, dilated cardiomyopathy, and heart failure. Whereas JYNNEOS and modified vaccinia Ankara are associated with minor cardiovascular adverse events such as tachycardia, palpitation, electrocardiogram changes such as T wave inversion, and ST elevation. Conclusions: Despite having cardiovascular issues with the existing vaccines, clinicians and public health experts should measure the risk benefit aspect of smallpox vaccines to decide whether to go for mass immunization or not. Based on the lessons learned from the COVID-19 pandemic, immunization will be a better strategy to halt the monkeypox spread throughout the globe. However, further research is needed to determine the exact incidence and susceptibility to develop cardiovascular complications among monkeypox immunized individuals.