Pathogen and Antibody Identification in Children with Encephalitis in Myanmar.

OBJECTIVE: Prospective studies of encephalitis are rare in regions where encephalitis is prevalent, such as low middle-income Southeast Asian countries. We compared the diagnostic yield of local and advanced tests in cases of pediatric encephalitis in Myanmar. METHODS: Children with suspected subacute or acute encephalitis at Yangon Children's Hospital, Yangon, Myanmar, were prospectively recruited from 2016-2018. Cohort 1 (n = 65) had locally available diagnostic testing, whereas cohort 2 (n = 38) had advanced tests for autoantibodies (ie, cell-based assays, tissue immunostaining, studies with cultured neurons) and infections (ie, BioFire FilmArray multiplex Meningitis/Encephalitis multiplex PCR panel, metagenomic sequencing, and pan-viral serologic testing [VirScan] of cerebrospinal fluid). RESULTS: A total of 20 cases (13 in cohort 1 and 7 in cohort 2) were found to have illnesses other than encephalitis. Of the 52 remaining cases in cohort 1, 43 (83%) had presumed infectious encephalitis, of which 2 cases (4%) had a confirmed infectious etiology. Nine cases (17%) had presumed autoimmune encephalitis. Of the 31 cases in cohort 2, 23 (74%) had presumed infectious encephalitis, of which one (3%) had confirmed infectious etiology using local tests only, whereas 8 (26%) had presumed autoimmune encephalitis. Advanced tests confirmed an additional 10 (32%) infections, 4 (13%) possible infections, and 5 (16%) cases of N-methyl-D-aspartate receptor antibody encephalitis. INTERPRETATION: Pediatric encephalitis is prevalent in Myanmar, and advanced technologies increase identification of treatable infectious and autoimmune causes. Developing affordable advanced tests to use globally represents a high clinical and research priority to improve the diagnosis and prognosis of encephalitis. ANN NEUROL 2023;93:615-628.

HPMC/PVP Dissolving Microneedles: a Promising Delivery Platform to Promote Trans-Epidermal Delivery of Alpha-Arbutin for Skin Lightening.

Alpha-arbutin is one of the most efficient skin lightener agents, which shows the effect on reducing the pigmentation by competitively inhibiting human tyrosinase. However, alpha-arbutin has difficulty in skin permeability due to its hydrophilic property. The objective of this study was, therefore, to develop alpha-arbutin-loaded dissolving microneedles (DMNs) for improving the delivery of alpha-arbutin into the skin. The DMN patch was prepared using Gantrez™ S-97, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone K-90 (PVP), chitosan, and their combinations. The optimal 8% alpha-arbutin-loaded DMNs, aside from Gantrez™ S-97, was successfully formulated with combination of 8% w/w HPMC and 40% w/w PVP K-90 (HPMC/PVP) at the weight ratio of 1:1. Both DMNs had 100% of penetration into porcine skin. Over 12 h of skin permeation, the flux of Gantrez™ S-97 DMNs and the HPMC/PVP DMNs were 66.21 µg/cm2/h and 74.24 µg/cm2/h, respectively. The accumulation amount of alpha-arbutin in the skin from Gantrez™ S-97 DMNs and HPMC/PVP DMNs was 107.76 µg and 312.23 µg, respectively. In comparison to the gel formulations, Gantrez™ S-97 DMNs and HPMC/PVP DMNs increase the delivery of alpha-arbutin across the skin approximately 2 and 4.7 times, respectively. In vivo studies found that alpha-arbutin-loaded HPMC/PVP DMNs delivered more alpha-arbutin into the skin than commercial cream. Moreover, the skin can reseal naturally after removal of DMNs patch without any signs of infection and remain stable in accelerated conditions for 4 weeks. Accordingly, alpha-arbutin-loaded HPMC/PVP DMNs could be a promising delivery platform for promoting trans-epidermal delivery of alpha-arbutin for skin lightening.

Plasma galectin-9 relates to cognitive performance and inflammation among adolescents with vertically acquired HIV.

OBJECTIVE: Adolescents with perinatally acquired HIV (AWH) are at an increased risk of poor cognitive development yet the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multimorbidity in adults with HIV despite antiretroviral therapy (ART); however, the relationship between Gal-9 in AWH and cognition remain unexplored. DESIGN: A cross-sectional study of two independent age-matched cohorts from India [AWH on ART ( n  = 15), ART-naive ( n  = 15), and adolescents without HIV (AWOH; n  = 10)] and Myanmar [AWH on ART ( n  = 54) and AWOH ( n  = 22)] were studied. Adolescents from Myanmar underwent standardized cognitive tests. METHODS: Plasma Gal-9 and soluble mediators were measured by immunoassays and cellular immune markers by flow cytometry. We used Mann-Whitney U tests to determine group-wise differences, Spearman's correlation for associations and machine learning to identify a classifier of cognitive status (impaired vs. unimpaired) built from clinical (age, sex, HIV status) and immunological markers. RESULTS: Gal-9 levels were elevated in ART-treated AWH compared with AWOH in both cohorts (all P  < 0.05). Higher Gal-9 in AWH correlated with increased levels of inflammatory mediators (sCD14, TNFα, MCP-1, IP-10, IL-10) and activated CD8 + T cells (all P  < 0.05). Irrespective of HIV status, higher Gal-9 levels correlated with lower cognitive test scores in multiple domains [verbal learning, visuospatial learning, memory, motor skills (all P  < 0.05)]. ML classification identified Gal-9, CTLA-4, HVEM, and TIM-3 as significant predictors of cognitive deficits in adolescents [mean area under the curve (AUC) = 0.837]. CONCLUSION: Our results highlight a potential role of Gal-9 as a biomarker of inflammation and cognitive health among adolescents with perinatally acquired HIV.

A Case Report of Cannabis Abuse: A Surprising Etiology of Elevated Troponin.

Cannabis is the most commonly used additive drug after alcohol and tobacco. There has been literature proving the relationship between cannabis use and elevated troponin from myocardial infarction, with many mechanisms explaining them. However, limited data are available on elevated troponin due to cannabis-induced high myocardial oxygen demand due to vasospasm. We present a case of a 21-year-old female presenting with chest pain after cannabis abuse. She exhibited a steep rise in troponin with a normal electrocardiogram (EKG). She refused a coronary angiogram, but a bedside echocardiogram showed no wall motion abnormality. Therefore, the dramatic rise of troponin levels with the chest pain and the resolution of the symptoms were most likely explained by demand ischemia via the mechanism of reversible vasospasm.

Workup and Management of Recurrent Attacks of Post-bariatric Hypoglycemia in a Patient With Non-alcoholic Steatohepatitis.

Bariatric surgery is an established treatment option for patients with non-alcoholic fatty liver disease (NAFLD) as well as non-alcoholic steatohepatitis (NASH) and is said to effectively reduce hepatic inflammation as well as steatosis in these patients. However, bariatric surgery is associated with multiple complications, including nutritional deficiencies, malnutrition, post-bariatric hypoglycemia (PBH), anastomotic leaks, and bowel strictures. This case report describes a rare but significant complication of post-bariatric surgery hypoglycemia in a patient with NASH, which started almost six months after Roux-en-Y gastric bypass (RYGB) surgery. This 55-year-old male patient presented with recurrent episodes of severe hypoglycemia, which, on further work-up, were found to be predominantly nocturnal as well as occurring two to three hours after meals. We report the successful treatment of the patient with an unconventional approach using nifedipine and acarbose. Our findings emphasize the importance of careful evaluation of patients who have undergone bariatric surgery, as this complication can occur as early as six months following the bariatric surgery as well as several years after the surgery. Our case report highlights the need for early recognition, relevant workup, and appropriate management of resistant hypoglycemic events using calcium channel blockers and acarbose, thus adding to the existing literature on this topic.

A novel bidirectional LSTM deep learning approach for COVID-19 forecasting.

COVID-19 has resulted in significant morbidity and mortality globally. We develop a model that uses data from thirty days before a fixed time point to forecast the daily number of new COVID-19 cases fourteen days later in the early stages of the pandemic. Various time-dependent factors including the number of daily confirmed cases, reproduction number, policy measures, mobility and flight numbers were collected. A deep-learning model using Bidirectional Long-Short Term Memory (Bi-LSTM) architecture was trained on data from 22nd Jan 2020 to 8 Jan 2021 to forecast the new daily number of COVID-19 cases 14 days in advance across 190 countries, from 9 to 31 Jan 2021. A second model with fewer variables but similar architecture was developed. Results were summarised by mean absolute error (MAE), root mean squared error (RMSE), mean absolute percentage error (MAPE), and total absolute percentage error and compared against results from a classical ARIMA model. Median MAE was 157 daily cases (IQR: 26-666) under the first model, and 150 (IQR: 26-716) under the second. Countries with more accurate forecasts had more daily cases and experienced more waves of COVID-19 infections. Among countries with over 10,000 cases over the prediction period, median total absolute percentage error was 33% (IQR: 18-59%) and 34% (IQR: 16-66%) for the first and second models respectively. Both models had comparable median total absolute percentage errors but lower maximum total absolute percentage errors as compared to the classical ARIMA model. A deep-learning approach using Bi-LSTM architecture and open-source data was validated on 190 countries to forecast the daily number of cases in the early stages of the COVID-19 outbreak. Fewer variables could potentially be used without impacting prediction accuracy.

Fabrication of polyvinyl pyrrolidone-K90/Eudragit RL100-based dissolving microneedle patches loaded with alpha-arbutin and resveratrol for skin depigmentation.

Alpha-arbutin (AA) and resveratrol (Res) are widely used in skin-lightening products. However, current topical formulations have minimal skin-lightening effects due to the low absorption and poor solubility of these active compounds. This study investigated the efficacy and safety of using dissolving microneedle (DMN) patches to improve the delivery of AA and Res for skin depigmentation. The DMN patches (F0-F3) fabricated from polyvinyl pyrrolidone-K90 (PVP-K90)/Eudragit RL100 blends successfully penetrated excised porcine skin and showed sufficient mechanical strength to resist compression forces. Loading DMNs with 10% AA and 2% Res at a ratio of 5 : 1 (F3) resulted in a synergistic interaction between the drugs with desirable dissolving ability, drug loading, and stability. Furthermore, both in vitro and in vivo studies revealed that the use of F3 DMN patches successfully enhanced the intradermal delivery of AA and Res over a 24 h period, with the delivered amount being higher (∼2.6 times) than that provided by a cream formulation (P < 0.05). After removing the DMN patches, the mice's skin was spontaneously and completely resealed within 12 h. In clinical studies, F3 DMN patches slightly decreased the melanin index of the participants without causing skin irritation or erythema at any time during the 24 h period when the patches were applied (P < 0.05). Moreover, application of the patches for 24 h was not found to affect skin hydration, transepidermal water loss, or skin elasticity. Therefore, AA/Res-loaded DMN patches could offer a promising approach for the effective local delivery of cosmetic agents for skin depigmentation.

A film-based intervention to reduce child maltreatment among migrant and displaced families from Myanmar: Protocol of a pragmatic cluster randomized controlled trial.

BACKGROUND: Child maltreatment is a global public health crisis with negative consequences for physical and mental health. Children in low- and middle-income countries (LMIC)-particularly those affected by poverty, armed conflict, and forced migration-may be at increased risk of maltreatment due to heightened parental distress and disruptions to social support networks. Parenting interventions have been shown to reduce the risk of child maltreatment as well as improve a range of caregiver and child outcomes, yet large-scale implementation remains limited in low-resource displacement settings. This study will examine the impact of an entertainment-education narrative film intervention on reducing physical and emotional abuse and increasing positive parenting among migrant and displaced families from Myanmar living in Thailand. METHOD: The study is a pragmatic, superiority cluster randomized controlled trial with approximately 40 communities randomized to the intervention or treatment as usual arms in a 1:1 ratio. Participating families in the intervention arm will be invited to attend a community screening of the film intervention and a post-screening discussion, as well as receive a poster depicting key messages from the film. Primary outcomes are changes in physical abuse, emotional abuse, and positive parenting behaviour. Secondary outcomes include caregiver knowledge of positive parenting, caregiver attitudes towards harsh punishment, caregiver psychological distress, and family functioning. Outcomes will be assessed at 3 time points: baseline, 4 weeks post-intervention, and 4-month follow up. A mixed methods process evaluation will be embedded within the trial to assess intervention delivery, acceptability, perceived impacts, and potential mechanisms of change. DISCUSSION: To our knowledge, this study will be the first randomized controlled trial evaluation of a film-based intervention to reduce child maltreatment among migrant and displaced families in a LMIC. An integrated knowledge translation approach will inform uptake of study findings and application to potential scale up pending evaluation results. TRIAL REGISTRATION: The study was prospectively registered with the Thai Clinical Trials Registry on 22 February 2023 (TCTR20230222005).

Intussusception risk following oral monovalent rotavirus vaccination in 3 Asian countries: A self-control case series evaluation.

Rotavirus vaccines have substantially decreased rotavirus hospitalizations in countries where they have been implemented. In some high- and middle-income countries, a low-level of increased risk of intussusception, a type of acute bowel obstruction, has been detected following rotavirus vaccination. However, no increased risk of intussusception was found in India, South Africa, or a network of 7 other African countries. We assessed the association between a 2-dose monovalent rotavirus vaccine (Rotarix) and intussusception in 3 early-adopter low-income Asian countries -- Afghanistan, Myanmar, and Pakistan. Children <12 months of age admitted to a sentinel surveillance hospital with Brighton level 1 intussusception were eligible for enrollment. We collected information about each child's vaccination status and used the self-controlled case series method to calculate the relative incidence of intussusception 1-7 days, 8-21 days, and 1-21 days following each dose of vaccine and derived confidence intervals with bootstrapping. Of the 585 children meeting the analytic criteria, the median age at intussusception symptom onset was 24 weeks (IQR: 19-29). Overall, 494 (84 %) children received the first Rotarix dose and 398 (68 %) received the second dose. There was no increased intussusception risk during any of the risk periods following the first (1-7 days: 1.01 (95 %CI: 0.39, 2.60); 8-21 days: 1.37 (95 %CI: 0.81, 2.32); 1-21 days: 1.28 (95 %CI: 0.78, 2.11)) or second (1-7 days: 0.81 (95 %CI: 0.42, 1.54); 8-21 days: 0.77 (95 %CI: 0.53, 1.16); 1-21 days: 0.78 (95 %CI: 0.53, 1.16)) rotavirus vaccine dose. Our findings are consistent with other data showing no increased intussusception risk with rotavirus vaccination in low-income countries and add to the growing body of evidence demonstrating safety of rotavirus vaccines.

Disseminated Histoplasmosis Presenting as Acute Respiratory Distress Syndrome and Disseminated Intravascular Coagulation in an HIV Positive Immigrant from Central America.

Histoplasmosis rarely causes significant illness in immunocompetent patients. In endemic areas such as the Midwestern United States and Central America, most people are infected, but are rarely symptomatic, with variable presentation. The illness is usually self-limited in immunocompetent individuals. However, in immunocompromised patients, Histoplasma capsulatum can disseminate to various organs and should be suspected especially in the endemic areas or if there is a significant travel history involving these areas. We present a case of a 65-year-old male originally from Central America with no known past medical history presenting with Acute Respiratory Distress Syndrome complicated by disseminated intravascular coagulation due to acute histoplasmosis and incidentally found to have HIV/AIDS.

Jejunal-Ileal Diverticulosis Induced Witzel Tube Failure: A Rare Cause of Small Bowel Obstruction.

Jejunal diverticulitis is a rare form of diverticulosis that occurs in the jejunum. Ileal diverticula are a type of false diverticula that are mostly asymptomatic and are usually discovered on imaging as incidental findings. Jejunal diverticula are typically difficult to diagnose pre-operatively due to their indolent and asymptomatic nature. The etiology of this condition is unclear, although some are believed to be genetic if diffuse. When symptomatic, patients may present with vague symptoms. This requires a high index of clinical suspicion because imaging results are usually negative. Management often requires surgical intervention in the presence of complications. Our case highlights a rare case of jejunal-ileal diverticulosis with inward involution causing Witzel tube (jejunostomy tube, or J-tube) obstruction and failure, along with partial obstruction of the small bowel.

Sudden Vasopressin Withdrawal Causing Transient Central Diabetes Insipidus: A Case Report.

Vasopressin is a peptide hormone produced by the hypothalamus and stored in the posterior pituitary. It is secreted in response to hypotension and hyperosmolarity. Vasopressin and its analogs have been widely used in vasodilatory shocks such as septic shock and cardiogenic shock. The sudden withdrawal of vasopressin after its prolonged use can lead to polyuria and rising sodium levels, which is concerning for the diagnosis of diabetic insipidus (DI); likely central rather than nephrogenic in origin. We present a case of diabetic insipidus following the sudden discontinuation of a prolonged vasopressin infusion for septic shock, which responded to tapering doses of desmopressin.

Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC), formerly called arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/ARVC), is a myocardial structural abnormality disease with clinical presentation of cardiac arrhythmia. It is characterized by the replacement of the myocardium with fibrofatty tissue. We present a case of a young male who met two major criteria for definite diagnosis of ARVC: early transition inverted t waves in lead V1-V4 and MRI showed right ventricle (RV) dyskinesia with RV ejection fraction (EF) < 40%, both satisfying the two major criteria of EKG and MRI required for definitive diagnosis.

Urinary Tract Infection Causing Bradycardia, Renal Failure, Atrioventricular Nodal Blockade, Shock, and Hyperkalemia (BRASH) Syndrome: A Case Report and a Brief Review of the Literature.

Bradycardia, renal failure, atrioventricular (AV) nodal blockade, shock, and hyperkalemia (BRASH) syndrome commonly occurs in the elderly population with compromised renal function and a history of taking AV nodal blocking agents on a regular basis. Hypovolemia and worsening of renal function are considered to be the major risk factors. BRASH syndrome should be differentiated from pure intoxication with AV nodal blocking agents, as the therapeutic goals of these conditions are different from each other. It encompasses a vicious cycle of bradycardia and decreased cardiac output leading to organ dysfunction including renal failure with hyperkalemia, further augmenting bradycardia. It is usually associated with high morbidity and mortality. Typically, the treatment involves increasing renal blood flow by augmenting cardiac output using catecholamine infusion. Very rarely, interventions such as intralipid emulsion and continuous renal replacement therapy (CRRT) may be required on a case-to-case basis. Promptly recognizing the symptoms of BRASH syndrome can help to avoid diagnostic delays and reduce mortality rates.

Warfarin Failure in a Patient With Chronic Thromboembolic Pulmonary Hypertension: A Case Report and Literature Review.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension caused by chronic venous thromboembolism (VTE). Venous thromboembolism (VTE) manifests as deep vein thrombosis (DVT), progressing to pulmonary embolism (PE). Pulmonary endarterectomy (PEA) is the preferred therapeutic option as it provides vascular disobliteration. Long-term anticoagulation with warfarin or direct oral anticoagulants (DOACs) is recommended for patients at risk for recurrent DVT in poor surgical candidates. However, treatment failure remains a concern. We present a patient who had VTE despite long-term anticoagulation with warfarin who had failed treatment and developed VTE with a therapeutic dilemma to continue anticoagulation despite supratherapeutic international normalized ratio (INR).

Parvovirus Infection Leading to Severe Anemia in an Adult Patient With HIV Disease.

Individuals with human immunodeficiency virus (HIV) disease frequently suffer from anemia. The causes include anemia of chronic disease, vitamin B12 and iron deficiency, opportunistic infections (Mycobacterium tuberculosis, Pneumocystis jiroveci), HIV-related bone marrow suppression, AIDS-associated malignancies, and antiretroviral therapy (ART), specifically zidovudine. In HIV patients with advanced immunodeficiency, failure to produce neutralizing antibodies can lead to chronic parvovirus B19 (B19) infection. Normally, in persons with intact immunity, the progression of B19 is self-limited. However, in chronic B19 infection, it can lead to pure red cell aplasia (PRCA) and chronic anemia. In human immunodeficiency virus (HIV)-infected patients, B19-related anemia is rare and underdiagnosed. It has a great response to intravenous immunoglobulin (IVIG) therapy. Hence, early diagnosis and prompt treatment can significantly reduce mortality. In this article, we described the case of a 25-year-old male with HIV infection who presented with a headache. He had severe normocytic anemia with a low reticulocyte count. The workup for blood loss, hemolysis, hemoglobinopathy, and iron deficiency was negative. Because of extremely low reticulocytopenia with severe anemia, the investigations favored multiple myeloma, parvovirus infection, and bone marrow aspiration biopsy. He was tested for parvovirus B19 deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) test due to insufficient seroconversion. It turned out to be positive and he was treated with IVIG therapy.

Voriconazole-Induced Acute Liver Injury: A Case Report.

Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United States. Clinical presentation of drug-induced liver injury may vary from asymptomatic or subtle symptoms to encephalopathy with serious morbidity. Early discontinuation of the offending agent is important to prevent clinical deterioration. Occasionally, despite discontinuation, there may be worsening of liver failure with grim prognosis as we present in this case report. Here, we report a case of a 61-year-old lady with a past medical history of sarcoidosis, stage IV and severe pulmonary hypertension initially admitted for the management of COVID pneumonia. Her hospitalization was complicated by fungemia with Aspergillus for which voriconazole was initiated, and two weeks into the course, acute liver injury diagnosed was most probably related to voriconazole. Despite discontinuation, her condition deteriorated, eventually culminating in mortality.

A Rare Case of Intrapulmonary Sequestration With Multiple Feeding Arteries and an Anomalous Pulmonary Vein Draining Into the Azygos Vein.

Pulmonary sequestration is an isolated mass of lung tissue that has no identifiable bronchial communication and that receives its blood supply from one or more anomalous systemic arteries. The feeding vessel is the aorta or its major vessels and venous drainage usually is to the pulmonary veins to the left atrium. We present a rare case of intralobar sequestration in a 65-year-old man with multiple feeding arteries from the aorta and partial anomalous venous return draining into the azygos vein. He remained asymptomatic and this anomaly was detected incidentally when computed tomography (CT) scan of the chest with contrast was done to rule out pulmonary embolism.

Augmented Renal Clearance in a Case of Sepsis Leading to Vancomycin Failure Despite Increasing Dose As per the Estimated Glomerular Filtration Rate.

Augmented renal clearance (ARC) is a unique clinical scenario observed in critically ill patients. We present a case of a 30-year-old male with sepsis secondary to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia treated with vancomycin. ARC was observed in the patient with a maximum estimated glomerular filtration rate (eGFR) of 161.9 ml/min/1.73 m2, and therapeutic drug monitoring was used to adjust the vancomycin dosage. Despite the maximal recommended dose of vancomycin, the therapeutic vancomycin level was not achieved, leading to treatment failure and subsequent mortality. Our case report suggests the necessity of other strategies, such as early dose adjustment of vancomycin based on vancomycin clearance and continuous vancomycin infusion, not merely conventional adjustment based on eGFR and vancomycin levels.

Clinical and Radiological Dissociation in Massive Barium Aspiration.

Barium studies are commonly used to rule out gastrointestinal (GI) pathologies and sometimes they are associated with complications such as barium aspiration with heterogeneity in clinical features ranging from mild to severe symptoms. We present a case of large volume barium aspiration in a 73-year-old male with past medical history of dysphagia diagnosed with diffuse esophageal spasm. Barium is an inert material commonly used for GI tract study. Although complications associated with barium studies are rare, aspiration of barium can have dramatic findings resulting in mild to severe symptoms. Clinically patient had very minimal symptoms but radiographic studies appeared dramatic. Therefore, a clinical and radiographic paradox must be kept in mind when evaluating patients and reviewing large volume barium aspiration imaging. Our case remained asymptomatic and had no respiratory complaints, nor did he develop any respiratory distress post barium aspiration.