Spontaneous Coronary Artery Dissection and Fibromuscular Dysplasia: A Case Series and Genetic Links.

Spontaneous coronary artery dissection (SCAD) is a rare cause of myocardial infarction in young women. An association of fibromuscular dysplasia (FMD) with SCAD has been well established; a significant proportion of SCAD patients may have typical FMD findings in other noncoronary arteries. The current consensus recommends arterial imaging screening from head to pelvis using computed tomography angiography (CTA) or magnetic resonance angiography (MRA) in SCAD. Genetic testing for FMD should be considered in high-risk cases. We present two cases of SCAD associated with FMD and discuss the significance of genetic screening in such patients.

Considerations for Expanding Antimicrobial Resistance Surveillance Networks.

Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia (CAPTURA) gained insight into the range of national antimicrobial resistance (AMR) stakeholders' long-term visions for AMR surveillance networks. As national AMR networks mature, stakeholders often contemplate adding laboratories to the network to achieve greater representativeness, boost data quantity, or meet other goals. Therefore, stakeholders should carefully select laboratories for expansion based on their goals and several practical criteria. Based on CAPTURA experience, the key criteria a national network may consider when expanding its AMR surveillance network include location, laboratory ownership, access to linked clinical and prescription databases, logistical ease, a laboratory's collaborative spirit, laboratory practices and equipment, laboratory staffing and quality assessments, laboratory methods and specimen types, data cleanliness and completeness, and the quantity of AMR data.

Bivalirudin versus heparin in STEMI after BRIGHT-4 trial: an updated meta-analysis.

BACKGROUND: The use of bivalirudin-based anticoagulation over heparin-based anticoagulation for coronary percutaneous intervention has been debated for a long time. Multiple trials have shown promising benefits of bivalirudin over heparin therapy with the most recent addition being the BRIGHT-4 trial. We performed a meta-analysis to assess evidence from these trials, focusing on the coronary intervention of the STEMI population. METHODS: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023394701). Databases were searched for relevant articles published before January 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4. RESULTS: Out of 2375 studies evaluated, 13 randomized control trials with 24 360 acute ST-elevation myocardial infarction patients were included for analysis. The bivalirudin-based anticoagulation reduced the net clinical events (OR 0.75, CI 0.61-0.92), major adverse cardiac or cerebral events (OR 0.85, CI 0.74-0.98), any bleeding (OR 0.61, CI 0.45-0.83), major bleeding (OR 0.54, CI 0.39-0.75), all-cause mortality (OR 0.79, CI 0.67-0.92) and cardiac mortality (OR 0.78, CI 0.65-0.93) significantly without increasing the risk of any stent thrombosis (OR 0.92, 95% CI 0.52-1.61), definite stent thrombosis (OR 1.17, 95% CI 0.62-2.22) and acute stent thrombosis (OR 2.06, 95% CI 0.69-6.09) significantly at 30 days. CONCLUSION: Based on this meta-analysis, bivalirudin plus a post-PCI high-dose infusion-based anticoagulation during STEMI PCI has significant benefits over heparin therapy for cardiovascular outcomes without a significant increase in the risk of thrombotic outcomes.

Paradoxical Vocal Fold Dysfunction Mimicking Bronchial Asthma in a Young Female Patient.

Inducible laryngeal obstruction (ILO)/paradoxical vocal fold motion (PVFM) is a reversible narrowing of the larynx that results from vocal fold motion dysfunction. Distinguishing ILO from asthma can be challenging, as they can coexist, and standard tests may not be able to differentiate between the two. However, a flexible laryngoscopy can promptly diagnose ILO. Unfortunately, ILO is often overlooked as a potential cause when evaluating patients with sudden-onset breathing difficulties and respiratory distress. We present a case of a young female who sought frequent treatment at the emergency room (ER) with symptoms of shortness of breath (SOB), rapid heart rate, rapid breathing, and anxiety. Despite receiving treatment for acute asthma attacks, her symptoms persisted. During her most recent hospital admission, a flexible laryngoscopy revealed abnormal vocal fold movements, indicating paradoxical vocal fold dysfunction (PVFD) and muscle tension dysphonia (MTD). A comprehensive treatment approach involving speech therapy, pulmonology, and psychiatry led to significant clinical improvement. This case report highlights the importance of raising awareness among healthcare providers about ILO potentially mimicking bronchial asthma exacerbation.

A Rare Case of Diffuse Alveolar Hemorrhage Caused by Fentanyl-Laced Marijuana.

Synthetic fentanyl adulteration has become a significant threat to public safety. It is commonly mixed into other drugs of abuse to lower costs and increase its addictive potential. Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication associated with the use of fentanyl-laced products. Given the current trend, we anticipate an increase in the incidence of DAH. It is crucial to recognize and treat DAH early in its course for better outcomes. We present a case of DAH due to an overdose of marijuana laced with fentanyl, manifesting as hemoptysis, and provide a review of the current literature on the topic.

A large hiatal hernia causing frequent premature ventricular contractions with bigeminy: A case report and review of literature.

Most patients with hiatal hernia (HH) are asymptomatic; however, common symptoms include gastroesophageal reflux disease (GERD) and heart burn. Larger hernia can cause obstruction, ischemia of the bowel, volvulus of the contents of the hernial sac, respiratory distress, and rarely, cardiac abnormalities are also noted. Most reported cardiac abnormalities associated with HH include atrial fibrillation, atrial flutter, supraventricular tachycardia, and bradycardia. We present a rare case of a large HH causing frequent premature ventricular contractions in bigeminy form that resolved with surgical correction of HH and did not recur on subsequent Holter monitoring. We highlight the potential association between HH/GERD and cardiac arrhythmias and reinforce the need to keep HH/GERD as one of the working diagnoses in a patient with cardiac arrhythmia. Learning objective: •Large hiatal hernia can cause several arrhythmias such as atrial fibrillation, atrial flutter, supraventricular tachycardia, bradycardia, and premature ventricular contractions (PVCs).•It is essential to consider hiatal hernia and gastroesophageal reflux disease as one of the differentials in the work up of cardiac arrhythmias including PVCs.

A Rare Case of Thrombotic Thrombocytopenic Purpura (TTP) With Concurrent Renal Cell Carcinoma: Diagnostic and Therapeutic Challenges.

Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening thrombotic microangiopathy (TMA) that needs prompt identification and treatment. Disseminated malignancy-related TMA can potentially be misdiagnosed as TTP, and patients may be inappropriately subjected to therapeutic plasma exchange (TPE) with serious implications. Likewise, the presence of a concurrent cancer diagnosis in a patient with microangiopathic hemolytic anemia and thrombocytopenia may lead to suspicion of disseminated malignancy as the cause, delaying the TPE with serious outcomes. Testing for ADAMTS13 activity is diagnostic of TTP, but the results may take time. This poses a diagnostic and therapeutic dilemma that includes weighing the benefits of TPE for treating TTP and cancer treatment. We describe a rare case of immune-mediated TTP in a patient concurrently diagnosed with metastatic renal cell cancer. To our knowledge, this is the first case of TTP reported in patients with metastatic renal cell carcinoma (RCC) in a non-treatment-naive patient.

Cardiac MRI in myocardial infarction without obstructive coronary artery disease (MINOCA) helps arrive at correct diagnosis - A case report and discussion.

Myocardial infarction without obstructive coronary artery disease (MINOCA) is a common condition with estimated prevalence of 5 to 15 %. It is not a benign condition and diagnosing the exact underlying etiology can be challenging, but it is important to ensure appropriate management of MINOCA patients. Cardiac magnetic resonance imaging (CMRI) can be a valuable and non-invasive test to identify the underlying etiology, as well as to risk-stratify such patients. Both the European Society of Cardiology and the American Heart Association recommend CMRI in diagnostic work up of MINOCA patients. We report a case of an 83-year-old man who presented to the emergency department with atypical chest pain but had significantly elevated cardiac troponin levels, with non-obstructive coronary artery disease on left heart catheterization. Subsequent CMRI led to the diagnosis of acute myocarditis. He was medically managed with good clinical outcomes. We discuss this case in detail and highlight the role of CMRI in MINOCA patients. As our understanding of troponin elevation and its various mechanisms continues to evolve, cardiac MRI has a significant role in diagnosis and management, as demonstrated in our case. Learning objectives: 1.Illustrate the clinical relevance and diagnosis of myocardial infarction without obstructive coronary artery disease (MINOCA).2.Explain the role of cardiac magnetic resonance imaging in diagnosis and management of MINOCA.

Use of Venous Thromboembolism Prophylaxis in Hospitalized Patients: Knowledge and Practice Among Physicians in Nepal.

Introduction: Despite the importance of Venous Thromboembolism (VTE) prophylaxis in hospitalized patients, audits have shown inadequate use of VTE prophylaxis methods around the world. We aimed to assess knowledge, attitudes, and behaviors regarding VTE prophylaxis among clinicians in Nepal. Methodology: A cross-sectional questionnaire-based survey was conducted using an online survey platform. Results: 199 (60.7%) of the respondents were aware of the risk factors-based risk stratification approach to VTE prophylaxis in hospitalized patients. Only 154 (47%) of the physicians reported institute-based protocols for VTE prophylaxis. Conclusion: We found a significant lack of awareness on risk factors-based stratification strategy for VTE prevention practices among Nepalese physicians. We recommend educational efforts for Nepalese physicians on the overall impact of VTE on mortality and morbidity of hospitalized patients. Our study highlights the needs for adoption of institution-based protocols for VTE prophylaxis and prevention.

Mistreatment during childbirth and postnatal period reported by women in Nepal -a multicentric prevalence study.

INTRODUCTION: Trust of women and families toward health institutions has led to increased use of their services for childbirth. Whilst unpleasant experience of care during childbirth will halt this achievement and have adverse consequences. We examined the experience of women regarding the care received during childbirth in health institutions in Nepal. METHOD: A prospective cohort study conducted in 11 hospitals in Nepal for a period of 18 months. Using a semi-structured questionnaire based on the typology of mistreatment during childbirth, information on childbirth experience was gathered from women (n = 62,926) at the time of discharge. Using those variables, principal component analysis was conducted to create a single mistreatment index. Bivariate and multivariate linear regression analyses were conducted to assess the association of the mistreatment index with sociodemographic, obstetric and newborn characteristics. RESULT: A total of 62,926 women were consented and enrolled in the study. Of those women, 84.3% had no opportunity to discuss any concerns, 80.4% were not adequately informed before providing care, and 1.5% of them were refused for care due to inability to pay. According to multivariate regression analysis, women 35 years or older (ß, - 0.3587; p-value, 0.000) or 30-34 years old (ß,- 0.38013; p-value, 0.000) were less likely to be mistreated compared to women aged 18 years or younger. Women from a relatively disadvantaged (Dalit) ethnic group were more likely to be mistreated (ß, 0.29596; p-value, 0.000) compared to a relatively advantaged (Chettri) ethnic group. Newborns who were born preterm (ß, - 0.05988; p-value, 0.000) were less likely to be mistreated than those born at term. CONCLUSION: The study reports high rate of some categories of mistreatment of women during childbirth. Women from disadvantaged ethnic group, young women, and term newborns are at higher risk of mistreatment. Strengthening health system and improving health workers' readiness and response will be key in experience respectful care during childbirth.

Payment mechanism for institutional births in Nepal.

BACKGROUND: Since the Millennium Development Goal era, there have been several efforts to increase institutional births using demand side financing. Since 2005, Government of Nepal has implemented Maternity Incentive Scheme (MIS) to reduce out of pocket expenditure (OOPE) for institutional birth. We aim to assess OOPE among women who had institutional births and coverage of MIS in Nepal. METHOD: We conducted a prospective cohort study in 12 hospitals of Nepal for a period of 18 months. All women who were admitted in the hospital for delivery and consented were enrolled into the study. Research nurses conducted pre-discharge interviews with women on costs paid for medical services and non-medical services. We analysed the out of pocket expenditure by mode of delivery, duration of stay and hospitals. We also analysed the coverage of maternal incentive scheme in these hospitals. RESULTS: Among the women (n-21,697) reporting OOPE, the average expenditure per birth was 41.5 USD with 36 % attributing to transportation cost. The median OOPE was highest in Bheri hospital (60.3 USD) in comparison with other hospitals. The OOPE increased by 1.5 USD (1.2, 1.8) with each additional day stay in the hospital. There was a difference in the OOPE by mode of delivery, duration of hospital-stay and hospital of birth. The median OOPE was high among the caesarean birth with 43.3 USD in comparison with vaginal birth, 32.6 USD. The median OOPE was 44.7 USD, if the women stayed for 7 days and 33.5 USD if the women stayed for 24 h. The OOPE increased by 1.5 USD with each additional day of hospital stay after 24 h. The coverage of maternal incentive was 96.5 % among the women enrolled in the study. CONCLUSIONS: Families still make out of pocket expenditure for institutional birth with a large proportion attributed to hospital care. OOPE for institutional births varied by duration of stay and mode of birth. Given the near universal coverage of incentive scheme, there is a need to review the amount of re-imbursement done to women based on duration of stay and mode of birth.

The Association of Childhood Pneumonia with Household Air Pollution in Nepal: Evidence from Nepal Demographic Health Surveys.

INTRODUCTION: Childhood pneumonia is a major cause of mortality worldwide while household air pollution (HAP) is a major contributor to childhood pneumonia in low and middle-income countries. This paper presents the prevalence trend of childhood pneumonia in Nepal and assesses its association with household air pollution. METHODS: The study analysed data from the 2006, 2011 and 2016 Nepal Demographic Health Surveys (NDHS). It calculated the prevalence of childhood pneumonia and the factors that cause household air pollution. The association of childhood pneumonia and HAP was assessed using univariate and multi-variate analysis. The population attributable fraction (PAF) of indoor pollution for causing pneumonia was calculated using 2016 NDHS data to assess the burden of pneumonia attributable to HAP factors. RESULTS: The prevalence of childhood pneumonia decreased in Nepal between 2006 and 2016 and was higher among households using polluting cooking fuels. There was a higher risk of childhood pneumonia among children who lived in households with no separate kitchens in 2011 [Adjusted risk ratio (ARR) 1.40, 95% CI 1.01-1.97] and in 2016 (ARR 1.93, 95% CI 1.14-3.28). In 2016, the risk of children contracting pneumonia in households using polluting fuels was double (ARR 1.98, 95% CI 1.01-3.92) that of children from households using clean fuels. Based on the 2016 data, the PAF for pneumonia was calculated as 30.9% for not having a separate kitchen room and 39.8% for using polluting cooking fuel. DISCUSSION FOR PRACTICE: Although the occurrence of childhood pneumonia in Nepal has decreased, the level of its association with HAP remained high.

Stunting Among Under 5-Year-Olds in Nepal: Trends and Risk Factors.

INTRODUCTION: The nutritional status in the first 5 years of life has lifelong and inter-generational impacts on individual's potential and development. This study described the trend of stunting and its risk factors in children under 5 years of age between 2001 and 2016 in Nepal. METHODS: The study used datasets from the 2001, 2006, 2011 and 2016 Nepal Demographic Health Surveys to describe the trend of stunting in under 5-year children. Multiple logistic regression analysis was carried out to assess the risk factors for stunting at the time of the four surveys. RESULTS: The nutritional status of under 5-year children improved between 2001 and 2016. Babies born into poorer families had a higher risk of stunting than those born into wealthier families (AOR 1.51, CI 95% 1.23-1.87). Families residing in hill districts had less risk of stunting than those in the Terai plains (AOR 0.75, CI 95% 0.61-0.94). Babies born to uneducated women had a higher risk of stunting than those born to educated women (AOR 1.57, CI 95% 1.28-1.92). DISCUSSION: Stunting among under-5-year children decreased in the years spanning 2001-2016. This study demonstrated multiple factors that can be addressed to decrease the risk of stunting, which has important implications for neurodevelopment later in life. We add literature on risk factors for stunting in under-5-year children.

Generation of a novel human cytomegalovirus bacterial artificial chromosome tailored for transduction of exogenous sequences.

The study of herpesviruses, including human cytomegalovirus (HCMV), is complicated by viral genome complexity and inefficient methods for genetic manipulation in tissue culture. Reverse genetics of herpesviruses has been facilitated by propagating their genomes in E. coli as bacterial artificial chromosomes (BACs), which enables complex and precise genetic manipulation using bacterial recombinational systems. Internal capsid volume imposes a strict limit on the length of genome that can be packaged efficiently. This necessitates deletion of presumably nonessential segments of the viral genome to allow for incorporation of the E. coli mini-F plasmid propagation sequence. To avoid deleting viral genes, several BACs utilize a Cre/LoxP system to self-excise the mini-F sequence upon reconstitution of virus in tissue culture. Here, we describe the adaptation of Cre/LoxP to modify the mini-F sequence of the HCMV TB40/E BAC, thus generating a new self-excisable BAC, TB40/E/Cre. After excision of the E. coli propagation sequence, a 2.7 kbp genome length deficit is created due to a preexisting deletion within the US2-US6 coding region. We exploited this deficit and an FKBP12 protein destabilization domain (ddFKBP) to create a novel gene transduction system for studying exogenous proteins during HCMV infection. Using TB40/E/Cre, we: i) found genome length-associated differences in growth and ii) demonstrated its utility as a system capable of efficient transduction of exogenous proteins and regulation of their accumulation over periods as short as 2h. TB40/E/Cre is a powerful tool of broad applicability that can be adapted to study HCMV replication and cell biology in a variety of contexts.

Mucormycosis of the Frontal Sinus: A Rare Case Report and Review.

Mucormycosis of the frontal sinus are rarely seen in day to day clinical practice. Although this fungus is commonly found in the environment, the disease is usually prevented by the immune system and is hence rare. Well-recognized risk factors for the disease include diabetes mellitus, leukemia, aplastic anemia, myelodysplastic syndrome, blood dyscrasias, and immunosuppressive therapy in organ transplantation, renal disease, sepsis, and severe burns. The disease is primarily found in those who are immunocompromised, but it may also manifest in immuno competent persons. Current therapy for the invasive disease includes early surgical debridement, antifungal therapy management of underlying predisposing factors. Early recognition of the disease and treating the underlying cause of mucormycosis, such as diabetes, are key to improving outcomes. The antifungal treatment of choice for mucormycosis is amphotericin B, although very high doses are required because of the relative resistance of the fungus to the drug. Here, we present a case of rhinocerebral mucormycosis of frontal sinus in a diabetic patient, who was managed by systemic antifungals, surgical debridement, and obliteration procedures.

Early Postoperative Malignant Subcutaneous Emphysema: Report and Review.

BACKGROUND: Subcutaneous emphysema is defined as presence of air or gas in subcutaneous tissue layer. It may be localized or generalized due to various aetiological factors. Although SE and pneumomediastinum are self-limiting conditions, life-threatening complications may develop. Escape of air into both pleural cavity causing bilateral pneumothorax and tension pneumothorax can be termed as malignant emphysema. PURPOSE: To report a case of malignant generalized subcutaneous emphysema in early postoperative phase following palatoplasty. CASE REPORT: A 25 year old female patient was operated for closure of residual oronasal communication using an anteriorly based tongue flap. The patient was reversed from general anesthesia and shifted to the post-operative room with the endotracheal tube in situ. Sudden swelling of the face and periorbital area was noticed which spread all over the body. A diagnosis of malignant post-operative subcutaneous emphysema was made and the patient was shifted back to the operation theatre. She was managed successfully by bilateral tube thoracotomy and tracheostomy. CONCLUSION: Close observation of the patient in early postoperative stage having endotracheal tube in situ is crucial to avoid such complication. Regardless of aetiology, early recognition of the clinical features of tension pneumothorax and timely intervention are necessary for the survival of the patient.

Distraction Osteogenesis for Management of Severe OSA in Pierre Robin Sequence: An Approach to Elude Tracheostomy in Infants.

BACKGROUND: Severe obstructive sleep apnoea (OSA) is a life threatening condition associated with Pierre Robin sequence (PRS) due to mandibular micrognathia and glossoptosis. Often these patients require tracheostomy at an early age which has high morbidity. Distraction osteogenesis (DO) is an accepted method of treatment for patients with hypoplastic mandible to achieve mandibular lengthening without need for a bone graft. It has also been used in respiratory distressed neonates and infants to avoid tracheostomy. CASE REPORT: An eight month old baby, a diagnosed case of PRS with severe OSA and recurrent episodes of aspiration pneumonia and on nasogastric tube feeding since birth was referred to us for evaluation and possibility of therapeutic augmentation of the mandible by DO. After a thorough clinico-radiological assessment the child was operated for bilateral extraoral placement of horizontal corpus distractor. A total distraction of 12 mm was carried out and consolidation of callus was monitored by USG. Postoperatively the patient was followed up for 12 months. Presently she has normal respiratory and feeding function without any episode of aspiration pneumonia. CONCLUSION: Mandibular corpus DO is a safe and effective technique that can be applied to predictably relieve severe upper airway obstruction in selected PRS cases. In order to avoid the limitations of alternative surgical procedures and the tracheostomy-associated morbidity, DO should be considered among the routine treatment modalities.

Efficacy and safety of linagliptin in type 2 diabetes patients with self-reported hepatic disorders: A retrospective pooled analysis of 17 randomized, double-blind, placebo-controlled clinical trials.

AIMS: Liver disease is highly prevalent among people with type 2 diabetes mellitus (T2DM). We evaluated the dipeptidyl peptidase-4 inhibitor linagliptin in subjects with T2DM and hepatic disorders. METHODS: Data were pooled from 17 randomized, double-blind, placebo-controlled clinical trials of linagliptin in T2DM subjects that included individuals with self-reported history of hepatic disorders at baseline. The primary endpoint was change in HbA1c from baseline to week 24. RESULTS: Of the 7009 participants (56% white, 39% Asian), 574 had hepatic disorders, most commonly hepatic steatosis (60%). At week 24, adjusted mean±standard error (SE) change in HbA1c from baseline in those with hepatic disorders was -0.75%±0.05 with linagliptin and -0.20%±0.08 with placebo [treatment difference: -0.54% (95% confidence interval-0.72 to -0.36); P<.0001]. There was no significant difference in HbA1c reduction between subjects with or without baseline hepatic disorders (P=.4042). Among subjects with hepatic disorders, 13.5% and 14.8% of the linagliptin and placebo groups, respectively, reported drug-related adverse events while 10.4% and 15.9%, respectively, reported hypoglycemia. Overall, adverse event rates were similar in individuals with or without hepatic disorders. CONCLUSIONS: This large pooled analysis suggests that linagliptin is effective and well tolerated in people with T2DM and liver disease.

Safety and efficacy of linagliptin in patients with type 2 diabetes mellitus and coronary artery disease: Analysis of pooled events from 19 clinical trials.

AIMS: To examine the safety and efficacy of linagliptin in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) using pooled data from the global clinical trials program. METHODS: Patient-level data were pooled from randomized, placebo-controlled clinical trials of linagliptin (5mg, monotherapy or combination therapy). Safety/efficacy analyses were conducted for patients with CAD and ≥12 and ≥24weeks of treatment, respectively. RESULTS: The safety analysis included 19 trials (linagliptin, n=451; placebo, n=272) and the efficacy analysis, 12 trials (linagliptin, n=328; placebo, n=198); mean (± standard deviation) exposure to study treatment was 212 (144) days linagliptin and 245 (171) days placebo. Occurrence of cardiac adverse events (AEs) was similar for linagliptin- and placebo-treated patients (9.1% and 9.2%, respectively); exposure-adjusted incidence rates (per 100 patient-years) were 16.6 and 14.0, respectively. Overall incidence of AEs was numerically lower with linagliptin than placebo. After 24weeks, mean adjusted change (standard error) from baseline glycosylated hemoglobin was -0.64% (0.04) with linagliptin vs. -0.08% (0.05) with placebo (P<.001). CONCLUSIONS: This comprehensive pooled analysis showed that addition of linagliptin to treatment regimens of patients with T2DM and CAD was not associated with an increased incidence of cardiac AEs, was well tolerated, and was effective.