Viral etiologies of acute liver failure.

Acute liver failure (ALF) is a rare cause of liver-related mortality worldwide, with an estimated annual global incidence of more than one million cases. While drug-induced liver injury, including acetaminophen toxicity, is the leading cause of ALF in the Western world, viral infections remain a significant cause of ALF and the most common cause in many developing nations. Given the high mortality rates associated with ALF, healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis, rapid treatment initiation when possible, and optimal management, which may include liver transplantation. This review aims to provide a summary of viral causes of ALF, diagnostic approaches, treatment options, and expected outcomes.

Effect of oil pulling on the Streptococcus mutans concentation in plaque around orthodontic brackets -A prospective clinical study.

INTRODUCTION: Fixed orthodontic appliances create areas of plaque stagnation leading to an increase in the volume, structure, and composition of plaque. This increases the chances of decalcification and white spot lesions. Oil pulling, an ancient practice involving swishing oil in the mouth, has demonstrated a significant reduction in plaque scores after 45 days, and a reduction in salivary Streptococcus mutans concentration in few studies done in nonorthodontic subjects. The aim was to compare the concentration of S. mutans in plaque around orthodontic brackets in patients using oil pulling with sesame oil and those on routine oral hygiene. SUBJECTS AND METHODS: Twenty subjects requiring fixed orthodontic treatment were divided into two equal groups: Group A-Oil pulling and Group B-Control. All subjects were instructed to follow common oral hygiene methods and in addition, Group A was instructed to perform oil pulling for 30 days starting 1 month after placement of fixed appliances. Plaque specimens were collected from labial surfaces of maxillary lateral incisors and quantification of S. mutans was done using real-time polymerase chain reaction. Mean and standard deviations for descriptive statistics, paired, and unpaired sample t-tests were analyzed. RESULTS: Comparison of S. mutans concentration between T1 and T2 demonstrated a significant difference in both control and study groups. The experimental group showed significantly lesser S. mutans concentration compared to the control group. CONCLUSIONS: Oil-pulling therapy with sesame oil resulted in a statistically significant reduction in the concentration of S. mutans in the plaque around orthodontic brackets.

An Atypical Presentation of Fabry Disease in a Patient With Nephrotic Syndrome: A Case Report.

Fabry disease is a rare X-linked lysosomal storage disorder that leads to the accumulation of globotriaosylceramide (Gb3) across various tissues, stemming from a deficiency in alpha-galactosidase A (GLA). This condition is characterized by a spectrum of clinical manifestations that can significantly complicate diagnosis. Classical symptoms typically include neuropathic pain, angiokeratomas, and significant involvement of the renal and cardiac systems. However, atypical presentations may obscure the underlying diagnosis, emphasizing the importance of maintaining a high level of clinical suspicion. This case report details the diagnostic journey of a 24-year-old female who initially presented with nephrotic syndrome, a presentation not commonly associated with Fabry disease. Subsequent genetic testing revealed a pathogenic variant in the GLA gene, confirming Fabry disease and highlighting the critical need for genetic analysis in cases of unexplained renal pathology. This case underscores the variability of Fabry disease presentations and the pivotal role of comprehensive diagnostic strategies in uncovering this complex disorder.

Spontaneous Intracranial Hypotension: Role of Computed Tomography-guided Cervical Epidural Blood Patch.

BACKGROUND: Lumbar epidural blood patch (EBP) is not successful in all cases of cerebrospinal fluid (CSF) leak, particularly in the cervicothoracic region. The present study is a retrospective analysis of a cohort of patients who had undergone computed tomography (CT)-guided cervical EBP for spontaneous intracranial hypotension (SIH) due to CSF leak in the cervical region. METHODS: We retrospectively collected data from March 2009 to 2020. Our inclusion criteria were (1) clinical syndrome associated with CSF leak, (2) headache coming on shortly after assuming the erect position and relief achieved by lying down, (3) CT myelography evidence of CSF leak in the cervical region, and (4) patient not responding to conservative management for 7 days. Exclusion criteria were patients with bleeding diathesis and infection. There were six females and four males. Ages ranged from 32 to 57, with an average of 42 years. On presentation, all patients underwent contrast-enhanced magnetic resonance imaging (MRI) and CT myelography. Cervical EBP was done under CT scan guidance. Assessment of headache was done on a 10-point numerical rating scale (NRS) before and after the procedure. Results are categorized into complete relief, partial relief, and no relief categories. RESULTS: Nine out of 10 patients were completely recovered. One patient was partially recovered. The average NRS scale was 9.6 before treatment, which became 0.4 after EBP. No neurological or vascular complications were seen. CONCLUSION: Computed tomography-guided cervical EBP is an optimum and effective way of treating SIH due to a leak in the cervical region. It has a higher success rate than lumbar EBP. However, prospective randomized controlled trials of cervical vs lumbar EBP will further validate our observation.

The Intersection of Migraine and Epistaxis: Clinical Observations and Analysis.

Migraine prevalence has risen over the last few decades, which may be attributed to lifestyle changes. Epistaxis is unusual in migraine. Here we present a case series of four patients, who are presented with headaches associated with epistaxis. A detailed history revealed cardinal symptoms of migraine according to the International Headache Society, including hemicranial throbbing headache of moderate to severe intensity lasting for a duration of four to 72 hours, along with associated features of nausea, vomiting, photophobia, and phonophobia. Investigations, including ENT (ear, nose, and throat) examination, nasal endoscopy, gastroscopy, bronchoscopy, hematological, and coagulation parameters, were negative. All patients were started on prophylactic treatment for migraine, and they responded well. Epistaxis occurs at the peak of headache following which symptoms tend to resolve. The pathophysiology behind this is stimulation of the trigeminovascular system leading to dilatation of external and internal carotid arteries.

Sleep in Myasthenia Gravis: A Questionnaire-Based Study.

BACKGROUND: Disturbed sleep and its impact on quality of life (QoL) are underrecognized in myasthenia gravis (MG). AIMS: To evaluate the quality of sleep in MG using standard sleep questionnaires and assess factors that determine sleep. SETTINGS AND DESIGN: Prospective, cross-sectional, hospital-based study. PATIENTS AND METHODS: Fifty patients on stable drug therapy for at least 1 month and age- and gender-matched controls were assessed using standard sleep questionnaires [Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and NIMHANS Comprehensive Sleep Disorders Questionnaire (NCSDQ)]. RESULTS: Myasthenia Gravis Foundation of America (MGFA) grade was I, IIA, IIB, IIIA, IIIB, and IVA in 11, 19, 3, 10, 6, and 1 respectively. The mean PSQI and ESS scores were similar in patients and controls. Patients with abnormal ESS (>10) were older and had greater neck circumference (P = 0.018 and <0.001). Body mass index was greater in patients with PSQI > 5 (P < 0.05). Age, gender, and clinical severity did not affect PSQI. Compared with ESS and PSQI, NCSDQ showed higher frequency of disturbed sleep, snoring, early morning headache, difficulty in initiation, and maintenance of sleep in MG, although the differences between patients and controls were not significant. No correlation was found between QoL and ESS or PSQI. CONCLUSION: Patients of MG with stable clinical course with adequate treatment have sleep quality comparable with healthy controls. Longitudinal assessment of sleep quality at multiple time points throughout the disease course and correlating with cross-sectional disease severity may further delineate the impact of disease on sleep and QoL.

Anthropogenic sources and liquid water drive secondary organic aerosol formation over the eastern Himalaya.

Atmospheric aerosols have a serious impact on altering the radiation balance of the vulnerable Himalayan atmosphere. Organic aerosol (OA), one of the least resolved aerosol fractions in the Himalayas, constrain our competence to assess their climate impacts on the region. Here we investigate water-soluble OA molecules in PM10 samples collected from March to May 2019 at Lachung (27.4°N and 88.4°E), a high-altitude location (2700 m a.s.l.) in the eastern Himalaya, to elucidate their origin and formation process. The dominance of oxalic acid (C2) reveals that water-soluble OA in the eastern Himalaya are atmospherically processed. Backward air mass trajectories and mass concentration ratios of organic tracers as well as relationships with inorganic species (K+, SO42-, NH4+) suggest an anthropogenic origin of water-soluble OA with significant atmospheric processing during long-range transport to the eastern Himalayan region. We used the thermodynamic prediction of aerosol liquid water (ALW) to examine the formation mechanism of secondary OA (SOA) such as oxalic acid. Correlations of ALW with SO42- and water-soluble organic matter show that ALW is sensitive to both anthropogenic sulfate and water-soluble organic compounds in Himalayan aerosols. A strong positive relationship of C2 acid with predicted ALW provides evidence of extensive SOA formation from precursors via aqueous phase photochemical processes. This inference is supported by positive correlations of C2 acid relative abundance with diagnostic mass concentration ratios of C2 acid to precursor molecules. Our findings underscore the importance of anthropogenic sources and ALW in SOA formation through aqueous phase processes in the eastern Himalaya.

Exploring the evidence for mitochondrial dysfunction and genetic abnormalities in the etiopathogenesis of tropical ataxic neuropathy.

Tropical ataxic neuropathy (TAN) is characterised by ataxic polyneuropathy, degeneration of the posterior columns and pyramidal tracts, optic atrophy, and sensorineural hearing loss. It has been attributed to nutritional/toxic etiologies, but evidence for the same has been equivocal. TAN shares common clinical features with inherited neuropathies and mitochondrial disorders, it may be hypothesised that genetic abnormalities may underlie the pathophysiology of TAN. This study aimed to establish evidence for mitochondrial dysfunction by adopting an integrated biochemical and multipronged genetic analysis. Patients (n = 65) with chronic progressive ataxic neuropathy with involvement of visual and/or auditory pathways underwent deep phenotyping, genetic studies including mitochondrial DNA (mtDNA) deletion analysis, mtDNA and clinical exome sequencing (CES), and respiratory chain complex (RCC) assay. The phenotypic characteristics included dysfunction of visual (n = 14), auditory (n = 12) and visual + auditory pathways (n = 29). Reduced RCC activity was present in 13 patients. Mitochondrial DNA deletions were noted in five patients. Sequencing of mtDNA (n = 45) identified a homoplasmic variant (MT-ND6) and a heteroplasmic variant (MT-COI) in one patient each. CES (n = 45) revealed 55 variants in nuclear genes that are associated with neuropathy (n = 27), deafness (n = 7), ataxia (n = 4), and mitochondrial phenotypes (n = 5) in 36 patients. This study provides preliminary evidence that TAN is associated with a spectrum of genetic abnormalities, including those associated with mitochondrial dysfunction, which is in contradistinction from the prevailing hypothesis that TAN is related to dietary toxins. Analysing the functional relevance of these genetic variants may improve the understanding of the pathogenesis of TAN.

Comprehensive Analysis of Dementia Types and Risk Factors: A Study From a Tertiary Care Center in India.

Background and objective Dementia is a prevalent clinical syndrome characterized by memory impairment and cognitive dysfunction. Its global burden is expected to rise significantly, particularly in low- and middle-income countries. Understanding the spectrum of dementia types and associated risk factors is crucial for effective management. This study aims to elucidate the demographic profiles, clinical types, and risk factors of newly diagnosed dementia cases at a tertiary care hospital in India. Methods and materials A cross-sectional, hospital-based observational study was conducted on 81 patients at the Department of Medicine, Dr. D. Y. Patil Medical College, Hospital, and Research Centre, Pimpri, Pune, from February 2022 to January 2024. Ethical approval was obtained, and written consent was obtained from participants. Clinical diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria, supported by cognitive assessment tools and laboratory/radiological investigations. Inclusion criteria encompassed individuals aged 18 years or older, presenting with clinical symptoms suggestive of dementia, having a Mini-Mental State Examination (MMSE) score of less than 24 and Montreal Cognitive Assessment (MoCA) score of less than 25, according to DSM-V criteria for dementia. Exclusion criteria included individuals with a history of head trauma or those below 18 years of age. Results Of the 81 participants, the majority (74.1%) were over 60 years old, with females comprising 59.3% of the sample. Alzheimer's disease was the most prevalent dementia subtype (34.5%), followed by vascular dementia (19.7%) and mixed dementia (13.5%). Other causes included Lewy body dementia (2.46%), Parkinson's dementia (4.9%), frontotemporal dementia (4.9%), and Creutzfeldt-Jakob disease (1.2%). Reversible causes accounted for a significant proportion of cases: alcohol-associated dementia (6.1%), hypothyroid-associated dementia (3.7%), HIV-associated dementia (2.46%), herpes simplex dementia (1.2%), neurosyphilis-associated dementia (1.2%), and normal pressure hydrocephalus (NPH)-associated dementia (2.4%). Analysis of risk factors revealed distinct patterns among different dementia types, emphasizing the role of cardiovascular and metabolic health. Conclusion This study provides insights into the demographic profiles, clinical types, and dementia risk factors in India. Addressing causes and managing cardiovascular/metabolic health is crucial for dementia prevention and management. Comprehensive care strategies and ongoing research efforts are essential for improving dementia outcomes and enhancing the quality of life for affected individuals and their families.

Clinicopathological Features of Amyloid Neuropathy: A Four Decade Experience.

BACKGROUND: Peripheral neuropathy is one of the manifestations of primary or familial amyloidosis. Published studies from India are limited. MATERIALS AND METHODS: We reviewed the clinical and pathological features of amyloid neuropathy diagnosed at our Institute over the last 39 years. RESULTS: Fifty-five cases of amyloid neuropathies were diagnosed between 1981 and 2019, constituting 0.28% of peripheral nerve biopsies (55/19,081). Age at presentation ranged from 24 to 81 years (mean-48 years) with male preponderance [M:F = 3.58:1]. Duration of symptoms at presentation varied from 3 months to 10 years (mean-2.31 years). Majority presented with small fiber neuropathy (85%). Pure sensory symptoms predominated in 23%, while 72% had sensorimotor neuropathy and 35.8% had autonomic involvement, with isolated autonomic failure in one patient. Amyloid neuropathy was clinically suspected in 22.6% of nonfamilial cases. Familial amyloid neuropathy was suspected in eight patients. Genetic testing detected ATTR and gelsolin mutation in one each of tested patients. Nerve biopsies revealed characteristic birefringent amyloid deposits stained mahogany brown by Congo red predominantly surrounding endoneurial microvessels (34.5%), also in perineurium and epineurium in 25.45% cases. Preferential loss of small diameter myelinated fibers was noted. Axonal degeneration or regeneration was conspicuously absent. CONCLUSION: Amyloid neuropathy is uncommon (0.28% of nerve biopsies in our series). Nerve biopsy is essential for the diagnosis. We report our experience of amyloid neuropathy and underscore the importance of making an assiduous search for amyloid deposits in the appropriate setting. Awareness of this entity is important for early diagnosis in the light of emerging therapeutic advances.

Panton-Valentine leucocidin gene in methicillin resistant Staphylococcus aureus isolated from tertiary care hospital in Nepal.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) expresses the Panton-Valentine leukocidin (PVL) virulence gene, which is associated with community and hospital-acquired severe MRSA infections. The objective of this study was to determine the prevalence and antibiotic susceptibility profile with a focus on the presence of the PVL gene among MRSA isolates in healthcare settings. METHODOLOGY: A total of 1,207 clinical specimens and 304 hospital environment swabs were collected in a tertiary care hospital in Nepal, and investigated following basic microbiological techniques. S. aureus was confirmed with the coagulase test. An antibiotic susceptibility test (AST) was performed by the Kirby-Bauer method and screening for MRSA was carried out by the cefoxitin disc diffusion method guided by the Clinical and Laboratory Standards Institute (CLSI), 2020. DNA was extracted and used in a polymerase chain reaction (PCR) to detect mecA and PVL genes. RESULTS: Of the 1,511 samples, 45 (2.9%) S. aureus (23 clinical and 22 environmental) were isolated. Among them, 69.6% (16/23) and 27.3% (6/22) were MRSA in clinical and environmental isolates, respectively. Twelve (52.2%) clinical isolates and seven (31.8%) environmental isolates were multidrug resistant. The majority of isolates were susceptible to vancomycin and linezolid. The PVL gene was detected in 18.2% (n = 4/22) of the MRSA isolates, of which three were from clinical sources and one was from an environmental swab. CONCLUSIONS: The prevalence of MRSA, and PVL-producing S. aureus were higher in the hospital setting. Hence, immediate and urgent implementation of infection control and sanitation measures are needed in the hospital.

Making Informed Choices On Incorporating Chemoprevention into carE (MiCHOICE, SWOG 1904): Design and methods of a cluster randomized controlled trial.

INTRODUCTION: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. METHODS/DESIGN: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. RESULTS/DISCUSSION: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. TRIAL REGISTRATION: NCT04496739.

Vaccines Induce Homeostatic Immunity, Generating Several Secondary Benefits.

The optimal immune response eliminates invading pathogens, restoring immune equilibrium without inflicting undue harm to the host. However, when a cascade of immunological reactions is triggered, the immune response can sometimes go into overdrive, potentially leading to harmful long-term effects or even death. The immune system is triggered mostly by infections, allergens, or medical interventions such as vaccination. This review examines how these immune triggers differ and why certain infections may dysregulate immune homeostasis, leading to inflammatory or allergic pathology and exacerbation of pre-existing conditions. However, many vaccines generate an optimal immune response and protect against the consequences of pathogen-induced immunological aggressiveness, and from a small number of unrelated pathogens and autoimmune diseases. Here, we propose an "immuno-wave" model describing a vaccine-induced "Goldilocks immunity", which leaves fine imprints of both pro-inflammatory and anti-inflammatory milieus, derived from both the innate and the adaptive arms of the immune system, in the body. The resulting balanced, 'quiet alert' state of the immune system may provide a jump-start in the defense against pathogens and any associated pathological inflammatory or allergic responses, allowing vaccines to go above and beyond their call of duty. In closing, we recommend formally investigating and reaping many of the secondary benefits of vaccines with appropriate clinical studies.

Hyponatremia in Guillain-Barre Syndrome: A Review of Its Pathophysiology and Management.

Guillain-Barre syndrome (GBS) is the commonest cause of acute polyradiculoneuropathy that requires hospitalization. Many of these patients experience systemic and disease-related complications during its course. Notable among them is hyponatremia. Though recognized for decades, the precise incidence, prevalence, and mechanism of hyponatremia in GBS are not well known. Hyponatremia in GBS patients is associated with more severe in-hospital disease course, prolonged hospitalization, higher mortality, increased costs, and a greater number of other complications in the hospital and worse functional status at 6 months and at 1 year. Though there are several reports of low sodium associated with GBS, many have not included the exact temporal relationship of sodium or its serial values during GBS thereby underestimating the exact incidence, prevalence, and magnitude of the problem. Early detection, close monitoring, and better understanding of the pathophysiology of hyponatremia have therapeutic implications. We review the complexities of the relationship between hyponatremia and GBS with regard to its pathophysiology and treatment.

A Real-World Observational Study to Evaluate the Safety and Effectiveness of Fluticasone Furoate-Oxymetazoline Fixed Dose Combination Nasal Spray in Patients with Allergic Rhinitis.

BACKGROUND: Allergic rhinitis (AR) has shown an increasing prevalence leading to a considerable medical and social burden. Nasal congestion is the cardinal symptom of AR, and the upper respiratory tract is most affected by this long-lasting ailment. Intranasal corticosteroids alleviate nasal congestion, along with other symptoms of AR, but their effect is not evident immediately. Oxymetazoline has a rapid onset of action, but its use should be limited to 3-5 days. OBJECTIVE: The study aimed to evaluate the safety and effectiveness of the fixed-dose combination nasal spray containing fluticasone furoate and oxymetazoline hydrochloride (FF + OXY) 27.5/50 mcg once daily in patients with AR in a real-world clinical setting. METHODS: The study was a prospective, open-label, single-arm, multicenter, real-world observational study conducted in patients with AR for a period of 28 days. Patients (n = 388) with a diagnosis of AR were treated with a combination of FF + OXY nasal spray. Total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total symptom score (TSS) were documented at baseline and at the end of study period. The overall effectiveness of treatment with FF + OXY was rated by the investigators as very good/good/satisfactory/poor (4-point Likert scale) for each patient. RESULTS: Treatment with FF + OXY resulted in significant reduction in the TNSS, TOSS and TSS, from 7.18 ± 3.38 at baseline to 0.20 ± 0.84 (p < 0.001), from 2.34 ± 2.29 at baseline to 0.09 ± 0.53 (p < 0.001), from 9.51 ± 4.94 at baseline to 0.29 ± 1.32 (p < 0.001) at 28 days respectively. With respect to effectiveness, the investigators reported very good effectiveness in 52.12% of patients. No serious adverse events were reported. CONCLUSION: The fixed-dose combination of once-daily fluticasone furoate and oxymetazoline hydrochloride nasal spray 27.5/50 mcg was effective in relieving the nasal congestion and reduction of TNSS, TOSS and TSS in patients suffering from AR. The combination was safe and well tolerated with no rebound congestion throughout the treatment period.

Non-invasive markers of inflammation in alcohol-associated liver disease: A scoping review.

Clinical manifestations of liver inflammation in alcohol-associated liver disease (ALD) can range from asymptomatic to severe alcoholic hepatitis. While biopsy is the gold standard for identifying liver inflammation, it is an invasive procedure with risks of bleeding, visceral damage, and infection. We aim to establish the state of the current literature on non-invasive markers of inflammation in ALD. We searched Ovid MEDLINE, Embase, and the Cochrane Library for original studies on the association between one or more non-invasive biomarker(s) and histological inflammation or hepatitis in ALD patients. Exclusion criteria were lack of histological data, abstract only, non-English-language articles, and animal studies. Two independent reviewers screened abstracts, reviewed full texts, and extracted data from included papers. Our search identified 8051 unique studies. Title and abstract screening resulted in 563 studies, and full-text screening resulted in 31 studies for final inclusion. The majority were single-center observational cohorts with an average sample size of 124. Review of these studies identified 44 unique biomarkers and 8 calculated scores associated with histological inflammation and/or hepatitis, in addition to a metabolomic panel of 468 metabolites. Six studies examined diagnostic accuracy for histological inflammation and/or hepatitis. The highest area under the receiver operating characteristic curve was 0.932 using a model based on four metabolites. This review highlights the available literature on non-invasive markers of inflammation in ALD. There is a dearth of studies that evaluate the diagnostic accuracy of these biomarkers, and larger studies are needed to confirm findings identified in small cohorts.