Role of innate immunological/inflammatory pathways in myelodysplastic syndromes and AML: a narrative review.

Dysregulation of the innate immune system and inflammatory-related pathways has been implicated in hematopoietic defects in the bone marrow microenvironment and associated with aging, clonal hematopoiesis, myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). As the innate immune system and its pathway regulators have been implicated in the pathogenesis of MDS/AML, novel approaches targeting these pathways have shown promising results. Variability in expression of Toll like receptors (TLRs), abnormal levels of MyD88 and subsequent activation of NF-κß, dysregulated IL1-receptor associated kinases (IRAK), alterations in TGF-ß and SMAD signaling, high levels of S100A8/A9 have all been implicated in pathogenesis of MDS/AML. In this review we not only discuss the interplay of various innate immune pathways in MDS pathogenesis but also focus on potential therapeutic targets from recent clinical trials including the use of monoclonal antibodies and small molecule inhibitors against these pathways.

Prevalence, Associated Factors, and Impact of Workplace Violence among Physicians.

BACKGROUND: There is a dearth of objective data and studies pertaining to the prevalence and consequences of workplace violence against physicians in Nepal. This study aims to assess the prevalence, associated factors, and implications of workplace violence on Nepalese physicians. METHODS: We conducted a cross-sectional study from March 2021 to August 2021. Nepal Medical Council-certified physicians currently working in Nepal were included in the study. Baseline characteristics, types of violence experienced, patterns, psychosocial impacts, and changes in patient management were collected. RESULTS: Out of 318 responses received, 302 responses met the inclusion criteria and were included in the final analysis. One-hundred and ninety (62.9%) respondents had ever faced workplace violence. Madhesh Province had the highest prevalence (81.5%). Verbal abuse (93.2%) was the most common type of violence encountered. We found a significant association between workplace violence and hours worked each week. We also found an association between workplace violence and years of experience. Our study found a significant increase in stress/depression/anxiety/idea of persecution, sense of defeat, job turnover, and loss of productivity/income with the increase in severity of workplace violence. CONCLUSIONS: Workplace violence is largely prevalent among Nepalese physicians. In the aftermath of workplace violence, a physician can undergo a multitude of adverse psychosocial consequences leading to a further decrease in productivity. More insights through research, formal training, and policy implementation are necessary to overcome this largely ignored problem of the medical fraternity in Nepal.

Air under the diaphragm-perforation or Chilaiditi sign?

Chilaiditi sign is a rare radiological finding in which the colon is interposed between the liver and the abdominal wall. Once patients become symptomatic, the condition is called Chilaiditi syndrome. We discuss a unique patient who presented with intermittent abdominal pain for 2 years that worsened 6 months before presentation. Her radiological evaluation revealed Chilaiditi sign. She was treated conservatively and the sign resolved. We emphasize the importance of conservative management in Chilaiditi syndrome.

Neurosarcoidosis Presenting as Young-Onset Chronic Headache: A Case Report.

Sarcoidosis causes granulomatous inflammation in multiple organ systems. Lungs are the most commonly affected organs. In 50% of the cases with lung involvement, other organs are also involved. The central nervous system is one of the rarer organ systems involved - comprising 5-15% of all the cases. Neurological involvement, when present, can affect virtually every part of the central and peripheral nervous system. We present an interesting case of a 30-year-old nonalcoholic, nonsmoker man who presented with a chronic headache of 6 years. He had a recent swaying of the body for 6 months and mild forgetfulness for 4 months. The patient had 2 episodes of facial nerve palsy in the past - which had responded to the treatment of Bell's palsy; however, the patient had some residual findings on presentation. While CSF findings suggested meningeal tuberculosis, the radiological evidence and biopsy confirmed the diagnosis of neurosarcoidosis. On follow-up after 6 weeks of steroid therapy, the patient displayed a marked improvement in headache, cognitive function, and a good response on imaging studies. Our case emphasizes that neurosarcoidosis should be considered in the differential diagnosis of chronic headaches and recurrent facial nerve palsy despite being very rare.

Cancer burden in Nepal, 1990-2017: An analysis of the Global Burden of Disease study.

INTRODUCTION: Cancer is the second leading cause of death and a major public health problem in the world. This study reports the trend and burden of cancer from 1990 to 2017 along with its risk factors in Nepal. METHODS: This study used the database of the Institute of Health Metrics and Evaluation's Global Burden of Diseases on cancer from Nepal to describe the most recent data available (2017) and trends by age, gender, and year from 1990 to 2017. The data are described as incidence, prevalence, disability-adjusted life years (DALY), and percentage change. RESULTS: In 2017, the age-standardized cancer incidence and mortality rates were 101.8/100,000 and 86.6/100,000 respectively in Nepal. Cancer contributed to 10% of total deaths and 5.6% of total DALYs in Nepal. The most common cancers were the breast, lung, cervical, stomach and oral cavity cancers. The number of new cancer cases and deaths in Nepal have increased from 1990 to 2017 by 92% and 95% respectively. On the other hand, age-standardized incidence and mortality rates decreased by 5% and 7% respectively. The leading risk factors of cancer were tobacco use, dietary factors, unsafe sex, air pollution, drug use, and physical inactivity. CONCLUSIONS: This study highlighted the burden of cancer in Nepal, contributing to a significant number of new cancer cases, deaths and DALY. A comprehensive approach including prevention, early diagnosis and treatment, and rehabilitation should be urgently taken to reduce the burden of cancer.

An Unusual Case of Tetanus Masquerading as an Acute Abdomen: A Case Report.

INTRODUCTION: Tetanus is an acute onset neurological disease that is often lethal. It has a high disease burden in low and middle-income countries. Tetanus is caused by a toxin made by spores of the bacterium Clostridium tetani, which are found in soil, dust, and animal feces. The toxin impairs the motor neurons leading to muscle stiffness. However, with the development of a toxoid vaccine, the incidence has sharply declined and is now categorized as a vaccine-preventable disease. The treatment of tetanus is primarily supportive and focuses on managing the complications until the effects of toxins resolve. CASE REPORT: We report the case of a 67-year-old farmer who previously sustained a laceration injury approximately 45 days prior to presenting to the emergency department with abdominal pain and rigidity. After a comprehensive evaluation to rule out other items in the differential diagnoses, he was diagnosed with tetanus based on clinical symptoms and ultimately required mechanical ventilation. The patient was then managed in the intensive care unit and later made an uneventful recovery. CONCLUSION: This case illustrates an uncommon presentation of tetanus and the latency of the infectious process. Often when patients present with atypical symptoms, it poses a diagnostic dilemma to the clinicians. Thus, it is very important to carefully elicit a history of contaminated injury. This case also highlights the importance of prophylactic vaccine in low and middle-income countries, which can reduce disease-related mortality and morbidity.

Experiences of cervical cancer survivors in Chitwan, Nepal: A qualitative study.

INTRODUCTION: Cervical cancer is a global leading cause of morbidity and mortality. The majority of cervical cancer deaths occur in developing countries including Nepal. Though knowledge of cervical cancer is an important determinant of women's participation in prevention and screening for cervical cancer, little is known about this topic in Nepal. This study explores the experiences of cervical cancer survivors and assesses the attitude of family and community towards it and stigma related to this disease in Bharatpur, Nepal. METHODS: The study design was qualitative methods involving two focus-group discussions. A total of 17 cervical cancer survivors, who have completed two years of cancer treatment were selected purposively from Chitwan. All qualitative data were transcribed and translated into English and were thematically analyzed. RESULTS: The majority of the participants had scant knowledge about cervical cancer, its causative agent, showed less cervical cancer screening, delayed healthcare-seeking behavior despite having persistent symptoms before the diagnosis. The main reasons identified for not uptaking the cervical screening methods were an embarrassment and having no symptoms at all. Most of them endured social stigma related to cervical cancer in the form of physical isolation and verbal abuse. CONCLUSIONS: There is an urgent need for interventions to make women and the public aware of cervical cancer and launch effective health education campaigns, policies for cervical cancer prevention programs. This implementation can save the lives of hundreds of women and help them avoid going through all the negative experiences related to cervical cancer. More studies are required to gain the perspectives, knowledge, experiences, and attitudes of cervical cancer survivors to add to the research.

Efficacy and safety of solriamfetol for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea: a systematic review and meta-analysis of clinical trials.

INTRODUCTION: Excessive daytime sleepiness (EDS) is the inability to maintain wakefulness and alertness during the major waking episodes of the day, with sleep occurring unintentionally or at inappropriate times. Solriamfetol is a selective norepinephrine-dopamine reuptake inhibitor approved for EDS. This review was done to assess the efficacy and safety of solriamfetol in patients with EDS in narcolepsy or OSA. METHODS: A systematic search of the electronic database was conducted for relevant studies. Any randomized controlled trial with outcome measures on the efficacy or safety of solriamfetol in EDS were eligible for inclusion. The primary outcomes were mean difference in the maintenance of wakefulness test (MWT), Epworth sleepiness scale (ESS) score, and risk ratio of adverse events. The random-effects model was used to calculate pooled effect estimates. RESULTS: We identified 336 records from the database search. We analyzed eight articles reported from six clinical trials. We pooled outcome measures from five trials. The overall mean difference for MWT was 9.93 min (95% CI: 8.25-11.61), and the mean difference of ESS score was -4.44 (95% CI: -5.50 to -3.38), both in favor of solriamfetol over placebo. The overall risk ratio of adverse events with solriamfetol was 1.47 (95% CI: 1.28-1.69). The most common adverse events reported were headache, nausea, decreased appetite, anxiety, nasopharyngitis, and insomnia. CONCLUSIONS: Solriamfetol is efficacious and has a favorable safety profile in the treatment of EDS in patients with narcolepsy and OSA. Solriamfetol is well tolerated and may be recommended for the treatment of EDS in these patients.