Prevalence of sleep disorders in patients with advanced cancer: a cross-sectional study.

Background: Patients with advanced cancer are more susceptible to develop sleep disorders like insomnia, restlessness, hypersomnolence, and sleep apnea due to a series of stressful events and side effects of chemotherapeutic agents. Poor sleep quality is associated with bad cancer outcomes and substandard quality of life. The authors assessed the prevalence of sleep disorders among advanced cancer patients in a tertiary center in Nepal. Methods: Patients with stage three and four solid malignancies were enrolled from February 2023 to July 2023 to assess their sleep status. The data were collected using the Pittsburgh Sleep Quality Index (PSQI) questionnaire, analyzed using the Statistical Package for the Social Sciences (SPSS) version 27, and subgroup exploration was done to assess the relationship of poor sleep quality with gender, marital status, malignancy type, and treatment received. An ethical clearance was obtained from the Institutional Review Committee (IRC). Results: The authors evaluated data from 357 patients in the study. Of them, 58.3% were female and 41.7% were male. The mean age of the patients was 51.1 years. Among total cancer patients, 56% had significant sleep disorders. A significant association was observed between the quality of sleep and gender, type of malignancy, and treatment methods (p value <0.05). A majority of the patients demonstrated increased sleep latency, struggling to fall asleep swiftly. Conclusions: More than half of the patients had poor sleep, which has an adverse impact on the prognosis of the disease and quality of life of cancer patients. Therefore, this aspect of cancer management requires special consideration for better quality of life and appropriate end-of-life care.

Safety of cold resection of non-ampullary duodenal polyps: Systematic review and meta-analysis.

Background and study aims Endoscopic resection has traditionally involved electrosurgical cautery (hot snare) to resect premalignant polyps. Recent data have suggested superior safety of cold resection. We aimed to assess the safety of cold compared with traditional (hot) resection for non-ampullary duodenal polyps. Methods We performed a systematic review ending in September 2022. The primary outcome of interest was the adverse event (AE) rate for cold compared with hot polyp resection. We reported odds ratios with 95% confidence intervals (CIs). Secondary outcomes included rates of polyp recurrence and post-polypectomy syndrome. We assessed publication bias with the classic fail-safe test and used forest plots to report pooled effect estimates. We assessed heterogeneity using I 2 index. Results Our systematic review identified 1,215 unique citations. Eight of these met inclusion criteria, seven of which were published manuscripts and one of which was a recent meeting abstract. On random effect modeling, cold resection was associated with significantly lower odds of delayed bleeding compared with hot resection. The difference in the odds of perforation (odds ratio [OR] 0.31 [95% confidence interval [CI] 0.05-2.87], P =0.2, I 2 =0) and polyp recurrence (OR 0.75 [95% CI 0.15-3.73], P =0.72, I 2 =0) between hot and cold resection was not statistically significant. There were no cases of post-polypectomy syndrome reported with either hot or cold techniques. Conclusions Cold resection is associated with lower odds of delayed bleeding compared with hot resection for duodenal tumors. There was a trend toward higher odds of perforation and recurrence following hot resection, but this trend was not statistically significant.

Breast Cancer among Cancer Patients Visiting the Department of Internal Medicine of a Tertiary Centre.

Introduction: Breast cancer is one of the most common cancers worldwide both in terms of incidence and mortality. Its incidence has been on an increasing trend in developing nations including Nepal, however, there is very limited evidence of its demographic profile in our setting. This study aimed to find out the prevalence of breast cancer among cancer patients visiting the Department of Internal Medicine of a tertiary centre. Methods: A descriptive cross-sectional study was conducted among cancer patients visiting the Department of Internal Medicine of a tertiary care centre using retrospectively collected data from 1 August 2022 to 30 July 2023 after obtaining ethical approval from the Institutional Review Committee. Histopathologically confirmed cancer patients were included and those with incomplete and duplicated data were excluded. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 2067 cancer patients, the prevalence of breast cancer was 102 (4.93%) (4.00-5.87, 95% Confidence Interval). The mean age was 50.51±2.08 years. The most commonly affected age group was 40 to 60 years constituting 61 (59.80%) patients. Histologically, invasive breast cancer of no special type was the most common and was found in 91 (89.22%) patients. Conclusions: The prevalence of breast cancer was similar to other studies done in similar settings. Keywords: breast cancer; cross-sectional study; demography; malignancy; prevalence.

Wernicke's Encephalopathy in Type 2 Achalasia: Case Report and Literature Review.

Achalasia is primarily a smooth muscle motility disorder of the esophagus driven by aberrant peristalsis and failure of sphincter relaxation. Notably, achalasia is a heterogeneous disease with primarily 3 possible pattern subtypes. According to the review of current cases and literature regarding achalasia, patients primarily present with dysphagia, usually to solids and, if progressed, to solids and liquids. Rarely, untreated achalasia may result in thiamine deficiency and present as Wernicke-Korsakoff syndrome (WKS). This acute neurologic condition primarily affects the central and peripheral nervous system and is known by the triad of ataxia, ophthalmoplegia, and confusion. Individuals who present with WKS typically have a notable history of chronic alcohol abuse with decreased thiamine intake and metabolism. Although less common, individuals with WKS may have a pertinent history of starvation, anorexia nervosa, and malnutrition. This case highlights a unique presentation of Wernicke's encephalopathy (WE) in a 30-year-old woman with severe type II achalasia complicated by a 60-pound weight loss in a span of 2 months. According to our literature review, there have only been 2 previously reported cases of severe achalasia leading to the development of WE. Considering the limited number of case reports available, WE must be in the differentials in patients with underlying achalasia, and our case report highlights this unusual presentation with corresponding brain imaging and manometry testing.

Outcome of ALL With ALL-BFM-95 Protocol in Nepal.

PURPOSE: Data on survival outcomes in patients with acute lymphoblastic leukemia (ALL) originating from Nepal are limited. We aim to present the real-world data on treatment outcomes of patients with de novo ALL treated with pediatric ALL-Berlin-Frankfurt-Muenster (BFM)-95 protocol in Nepal. PATIENTS AND METHODS: We used the medical records of 103 consecutive patients with ALL treated in our center from 2013 to 2016 to evaluate the overall survival (OS) and relapse-free survival (RFS) and analyzed the effects of clinicopathologic factors on survival outcomes in patients with ALL. RESULTS: The 3-year OS and RFS in the entire cohort was 89.4% (95% CI, 82.1 to 96.7) and 87.3% (95% CI, 79.8 to 94.7), with a mean OS and RFS of 79.4 months (95% CI, 74.2 to 84.5) and 76.6 months (95% CI, 70.8 to 82.4), respectively. Patients with prednisone good response (PGR) showed better mean OS and RFS, whereas complete marrow response on day 33 was associated with better mean OS alone. Patients with Philadelphia (Ph)-positive ALL showed worse mean RFS compared to those with Ph-negative status. On multivariate analysis, PGR (hazard ratio [HR], 0.11; 95% CI, 0.03 to 0.49; P = .004) and sagittal vein thrombosis (SVT; HR, 5.95; 95% CI, 1.30 to 27.18; P = .02) were the only independent predictors of OS and RFS, respectively. Adverse events on BFM-95 protocol included SVT (4.9%), peripheral neuropathy (7.8%), myopathy (20.4%), hyperglycemia (24.3%), intestinal obstruction (7.8%), avascular necrosis of femur (6.8%), and mucositis (46%). CONCLUSION: BFM-95 protocol appears to be a safe and effective strategy in adolescent and young adults and adult Nepalese population with ALL with a low toxicity profile.

Clinical, Laboratory and Radiological Features of Paragonimiasis Misdiagnosed as Pulmonary Tuberculosis.

Background: Paragonimiasis presents with nonspecific symptoms and radiologic findings, allowing for the possibility of misdiagnosis. Diagnosis is generally delayed due to lack of suspicion and presentation similar to pulmonary tuberculosis. Methods: A prospective observational study was carried out on 20 subjects at Civil Service Hospital of Nepal from March 2015 to June 2019 who presented with eosinophilia and pulmonary symptoms, and were treated empirically with Anti-tubercular therapy for suspicion of pulmonary tuberculosis. Results: The median age of the patient was 34 years. Mean blood absolute eosinophil count was 16678/ul. Fever was present in 80% (n=16). Cough was present in 90% (n=18). Pleural effusion was noticed in 100% (n=20). Chest computed tomography showed ground-glass opacities in 65% (n=13) of patients. Pleural fluid eosinophilia (>10%) was evident in all patients. Pleural fluid LDH was elevated in 85% (n=17) of patients. Similarly, ADA was high (>40U) in 75% (n= 15) of patients, and pleural fluid sugar was low in 80% (n=16) of patients. All patients (100%) gave a history of crab or snail consumption. Paragonimus egg was detected in five (25%) patients. Twenty patients fulfilled definite or probable diagnostic criteria of paragonimiasis. Ninety-five (n=19) patients responded to praziquantel. Conclusion: Unavailability of serologic tests or failure to demonstrate parasitic egg under the microscope should not discourage physicians to consider the diagnosis of paragonimiasis when marked eosinophilia, high LDH levels, and low glucose levels are identified in pleural fluid of a patient with a history of raw crab or snail consumption.

Advanced Hepatocellular Carcinoma in Adults Without Cirrhosis: A Single-Institution Retrospective Review.

Background: Although up to one in five cases of hepatocellular carcinoma (HCC) occurs in patients without cirrhosis, there is scarce literature characterizing non-cirrhotic HCC (NCHCC). Existing NCHCC research is primarily limited to surgical case series and there is a lack of data on unresectable NCHCC. Aim: The purpose of this retrospective review was to compare the characteristics of unresectable NCHCC and cirrhotic hepatocellular carcinoma (CHCC). Methods: A retrospective chart review of adult patients with unresectable HCC treated from 2007 to 2017 was performed at the University of Florida Shands Hospital. The data set was stratified into two cohorts: NCHCC and CHCC. Continuous variables were compared using Wilcoxon-Mann-Whitney tests and Kruskal-Wallis rank-sum tests. Categorical variables were compared using Pearson's Chi-squared tests and Fisher's exact tests. Overall survival was explored utilizing the Kaplan-Meier and log-rank method. Results: There were 1494 adult patients included in the final analysis, including 264 patients (17.7%) with NCHCC and 1230 patients (82.3%) with CHCC. Median age was 61.0 years old and median follow-up time was 30.2 months. NCHCC patients were older than CHCC patients (66.3 years vs 61.9 years; p < 0.0001). NHCC tumors were larger than CHCC tumors (7.92 ± 4.85 vs 4.38 ± 3.12 cm; p < 0.0001) and more likely to be associated with distant metastases (23.35% vs 15.91%; p = 0.0055). There was no difference in overall survival, with a median of 23.5 months in NCHCC and 22.4 months in CHCC (p = 0.9196). Conclusion: Our findings suggest that unresectable NCHCC and CHCC have unique characteristics but similar overall survival. To the best of our knowledge, this is the largest comparison of CHCC and NCHCC.

Malnutrition among Cancer Patients in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Malnutrition is one of the most frequent disorders among cancer patients. It is seen in 50-90% of cancer patients. This high prevalence of malnutrition is very concerning as it is associated with reduced effective treatment, functional status, quality of life and survival. The aim of the study was to find out the prevalence of malnutrition among cancer patients in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among 95 cancer patients in the Department of Clinical Oncology of a tertiary care centre from 25 January 2022 to 25 July 2022. Ethical approval was obtained from the Institutional Review Committee (Reference number: 1192/2078/79). Convenience sampling was done. Patients were screened using Patient-Generated Subjective Global Assessment for malnutrition. Point estimate and 95% Confidence Interval were calculated. Results: Among 95 cancer patients, 22 (23.15%) (15.10-32.90, 95% Confidence Interval) were malnourished. Conclusions: The prevalence of malnutrition was found to be lower than in other studies done in similar settings. Nutritional assessment and support should be an integral part of care for gastrointestinal cancer. Keywords: malnourishment; nutritional deficiency; screening.

Distress Screening among Patients with Hematological Malignancies: A Descriptive Cross-sectional Study.

INTRODUCTION: Distress is a major concern during diagnosis and treatment of hematological malignancies. The Distress Thermometer is a commonly used screening tool to detect distress. The objectives of this study was to know the prevalence and identify distress score among patients with hematological malignancies in Nepal. METHODS: A descriptive cross sectional study was carried out at the Hematology Unit of Civil Service Hospital after obtaining an ethical approval from the Institutional Review Committee (reference number 931/076/077). A convenient sampling technique was used for this study. Statistical Package for the Social Sciences version 20.0 was used. All patients within one week of diagnosis and before the start of definitive treatment of hematological malignancies were included in the study. National Comprehensive Cancer Network Psychosocial Distress Screening Tool was used to measure the seriousness of distress. RESULTS: A total of 100 patients were enrolled in the study, among them 56 (56%) were male and 44 (44%) were female. The mean distress score in our study was found to be 5.68±1.75. Mean distress score among male and female patients were 5.84±1.65 and 5.48±1.86 respectively. Thirty three percentage (n=33) of patient had mild distress whereas, sixty six percentage (n=67) of patients experienced moderate to severe distress. CONCLUSIONS: There was a significant level of distress among the patients with hematological malignancies in Nepal. Therefore, distress screening should be done to all the patients when initial diagnosis is made.

Dependence On Glycolysis Sensitizes BRAF-mutated Melanomas For Increased Response To Targeted BRAF Inhibition.

Dysregulated metabolism can broadly affect therapy resistance by influencing compensatory signaling and expanding proliferation. Given many BRAF-mutated melanoma patients experience disease progression with targeted BRAF inhibitors, we hypothesized therapeutic response is related to tumor metabolic phenotype, and that altering tumor metabolism could change therapeutic outcome. We demonstrated the proliferative kinetics of BRAF-mutated melanoma cells treated with the BRAF inhibitor PLX4720 fall along a spectrum of sensitivity, providing a model system to study the interplay of metabolism and drug sensitivity. We discovered an inverse relationship between glucose availability and sensitivity to BRAF inhibition through characterization of metabolic phenotypes using nearly a dozen metabolic parameters in Principle Component Analysis. Subsequently, we generated rho0 variants that lacked functional mitochondrial respiration and increased glycolytic metabolism. The rho0 cell lines exhibited increased sensitivity to PLX4720 compared to the respiration-competent parental lines. Finally, we utilized the FDA-approved antiretroviral drug zalcitabine to suppress mitochondrial respiration and to force glycolysis in our cell line panel, resulting in increased PLX4720 sensitivity via shifts in EC50 and Hill slope metrics. Our data suggest that forcing tumor glycolysis in melanoma using zalcitabine or other similar approaches may be an adjunct to increase the efficacy of targeted BRAF therapy.

Quantifying heterogeneity and dynamics of clonal fitness in response to perturbation.

The dynamics of heterogeneous clonal lineages within a cell population, in aggregate, shape both normal and pathological biological processes. Studies of clonality typically relate the fitness of clones to their relative abundance, thus requiring long-term experiments and limiting conclusions about the heterogeneity of clonal fitness in response to perturbation. We present, for the first time, a method that enables a dynamic, global picture of clonal fitness within a mammalian cell population. This novel assay allows facile comparison of the structure of clonal fitness in a cell population across many perturbations. By utilizing high-throughput imaging, our methodology provides ample statistical power to define clonal fitness dynamically and to visualize the structure of perturbation-induced clonal fitness within a cell population. We envision that this technique will be a powerful tool to investigate heterogeneity in biological processes involving cell proliferation, including development and drug response.