A case of disseminated angiosarcoma-like Kaposi sarcoma presenting with unusual vesiculobullous lesions.

Angiosarcoma-like Kaposi sarcoma represents a recently delineated rare histomorphologic variant of Kaposi sarcoma that can be difficult to distinguish from other vasoproliferative lesions. Conventional lesions of Kaposi sarcoma encompass patches, plaques, and nodules; however, rarely vesiculobullous lesions have been described. Angiosarcoma-like Kaposi sarcoma has never been previously reported to present with vesiculobullous lesions. Herein, we describe a unique case of disseminated angiosarcoma-like Kaposi sarcoma with vesiculobullous lesions as the initial manifestation of human immunodeficiency virus infection.

Prospect of Controlled Autoxidation to Produce High-Value Products from the Low-Value Petroleum Fractions.

Substantial amounts of low-value light petroleum fractions and low-value heavy petroleum fractions, such as light naphtha, HVGO, and vacuum residue, are generated during the upgrading and refining of conventional and unconventional petroleum resources. The oil industry emphasizes economic diversification, aiming to produce high-value products from these low petroleum fractions through cost-effective and sustainable methods. Controlled autoxidation (oxidation with air) has the potential to produce industrially important oxygenates, including alcohols, and ketones, from the low-value light petroleum fractions. The produced alcohols can also be converted to olefin through catalytic dehydration. Following controlled autoxidation, the low-value heavy petroleum fractions can be utilized to produce value-added products, including carbon fiber precursors. It would reduce the production cost of a highly demandable product, carbon fiber. This review highlights the prospect of developing an alternative, sustainable, and economic method to produce value-added products from the low-value petroleum fractions following a controlled autoxidation approach.

Sepsis Unveils T-cell Large Granular Lymphocytic Leukemia in the Setting of End-Stage Renal Disease: A Rare Hematologic Malignancy.

Large granular lymphocytic (LGL) leukemia is a rare chronic lymphoproliferative disorder originating from natural killer cells or T lymphocytes. In this report, we present the case of a 66-year-old female initially treated for sepsis, with methicillin-sensitive Staphylococcus aureus identified on initial blood culture prompting intravenous (IV) antibiotic therapy. The patient met systemic inflammatory response syndrome criteria upon admission due to severe neutropenia. Persistent fever led to neurological symptoms, and imaging revealed lung abnormalities along with chronic changes on the CT scan of the head. Multidisciplinary consultations were sought, resulting in treatment adjustments including antifungals and filgrastim. Flow cytometry and bone marrow biopsy confirmed the diagnosis of LGL leukemia.

Corrigendum: The outbreak of seasonal goat's brucellosis in the Swat ecosystem of Khyber Pakhtunkhwa.

No abstract available.

Improving the Quality and Completeness of Discharge Summaries at a Tertiary Care Hospital in Pakistan: A Quality Improvement Project.

Introduction Discharge summaries (DS) allow continued patient care after being discharged from the hospital. Only a few quality improvement projects (QIPs) focused on assessing and improving the quality and completeness of DS at tertiary care hospitals have been undertaken in Pakistan. This QIP aimed to evaluate and enhance the quality and completeness of DS at a tertiary care hospital in Pakistan to facilitate seamless healthcare transitions. Methods A QIP was conducted in the medical unit of a tertiary care hospital in Rawalpindi, Pakistan. The DS were assessed using the e-discharge summary self-assessment checklist devised by the Royal College of Physicians (RCP). This QIP was done by the plan, do, study, act (PDSA) cycle. The PDSA cycle comprised two audit cycles and an intervention in between them. The first audit cycle (AC) was conducted on 150 DS. Its duration was from March 2023 to June 2023. An educational workshop was conducted before the re-audit cycle (RAC) to address deficiencies and reinforce the implementation of the guidelines provided by the RCP. The RAC was conducted from June 2023 to August 2023. 100 DS were studied and analyzed to assess for improvement in the completeness of DS. Frequencies and percentages were calculated in each audit cycle. The Chi-squared test was applied to compare the statistical difference between the results of both audit cycles. Results A total of 150 DS were analyzed in the first AC and 100 DS in the RAC. The results of the first AC show that the details of any allergies were recorded only in 3% of the DS; this percentage significantly improved to 51% after the RAC (p-value <0.05). Relevant past medical history was included in 52% and 88% of the DS during the first AC and RAC, respectively (p-value <0.05). Secondary diagnoses were written in 54% and 71% of the DS during the first AC and RAC, respectively (p-value <0.05). Details of relevant investigations were included in 60% and 88% of the DS during the first AC and RAC, respectively (p-value <0.05). The post-discharge management plan was written in 90% and 98% of the DS during the first AC and RAC, respectively (p-value <0.05). The follow-up plan was written clearly in 65% and 93% of the DS during the first AC and RAC, respectively (p-value <0.05).  Conclusion The DS was found to be incomplete after analyzing the results of the first AC. The details related to allergies, medications, operations, and procedures were found to be missing in the majority of the cases. No mention of the patient's concerns or expectations was made in the DS. The results of the RAC showed improvement in the level of completeness of DS. The majority of the weak points observed after the first AC seemed to have improved after the RAC, which shows that intervention proved to be quite effective in improving the completeness and quality of DS. The RAC showed significant improvement in the completeness of the details relating to investigations, allergies, past medical history, secondary diagnoses, and the post-discharge follow-up plan. QIP must be routinely carried out to assess and improve the completeness and quality of DS at hospitals.

Single-Cell Analysis Identifies NOTCH3-Mediated Interactions between Stromal Cells That Promote Microenvironment Remodeling and Invasion in Lung Adenocarcinoma.

Cancer immunotherapy has revolutionized the treatment of lung adenocarcinoma (LUAD); however, a significant proportion of patients do not respond. Recent transcriptomic studies to understand determinants of immunotherapy response have pinpointed stromal-mediated resistance mechanisms. To gain a better understanding of stromal biology at the cellular and molecular level in LUAD, we performed single-cell RNA sequencing of 256,379 cells, including 13,857 mesenchymal cells, from 9 treatment-naïve patients. Among the mesenchymal cell subsets, FAP+PDPN+ cancer-associated fibroblasts (CAF) and ACTA2+MCAM+ pericytes were enriched in tumors and differentiated from lung-resident fibroblasts. Imaging mass cytometry revealed that both subsets were topographically adjacent to the perivascular niche and had close spatial interactions with endothelial cells (EC). Modeling of ligand and receptor interactomes between mesenchymal and ECs identified that NOTCH signaling drives these cell-to-cell interactions in tumors, with pericytes and CAFs as the signal receivers and arterial and PLVAPhigh immature neovascular ECs as the signal senders. Either pharmacologically blocking NOTCH signaling or genetically depleting NOTCH3 levels in mesenchymal cells significantly reduced collagen production and suppressed cell invasion. Bulk RNA sequencing data demonstrated that NOTCH3 expression correlated with poor survival in stroma-rich patients and that a T cell-inflamed gene signature only predicted survival in patients with low NOTCH3. Collectively, this study provides valuable insights into the role of NOTCH3 in regulating tumor stroma biology, warranting further studies to elucidate the clinical implications of targeting NOTCH3 signaling. SIGNIFICANCE: NOTCH3 signaling activates tumor-associated mesenchymal cells, increases collagen production, and augments cell invasion in lung adenocarcinoma, suggesting its critical role in remodeling tumor stroma.

Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys: Time for household-wide interventions?

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11-1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions.

Association of Obesity With Type 2 Diabetes Mellitus: A Hospital-Based Unmatched Case-Control Study.

Background The prevalence of type 2 diabetes mellitus (T2DM) and obesity is alarmingly increasing with the accessibility of the modern lifestyle. This study aimed to assess the association of obesity with T2DM among the patients visiting the Medicine Department of Ayub Teaching Hospital, Abbottabad, Pakistan. Method This hospital-based, unmatched case-control study was conducted from March 2022 to September 2022. A total of 200 patients (age ≥ 18) (100 cases and 100 controls) were recruited. Those patients with a history of T2DM were selected as cases, and those without diabetes were selected as controls after taking informed written consent. Patients with BMI ≥ 25 were considered obese. Data were collected through a non-probability convenience sampling technique using a self-structured non-validated questionnaire. Data were organized and analyzed through IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY). Results We found a significant positive association of obesity with T2DM with a crude odds ratio of 3.6 (95% CI: 2.0-6.6), a p-value of 0.000, and an adjusted odd ratio of 3.7 (95% CI: 1.9 - 7.1), with a p-value of 0.004 (adjusted for potential confounders, including gender, age group, stress, and status of physical activeness) using a logistic regression model. Conclusion It is concluded that obesity is strongly associated with developing T2DM and lack of physical activity, people over 45 years, and males with obesity have a higher chance of developing T2DM.

Direct Immunofluorescence of Skin and Oral Mucosa: Guidelines for Selecting the Optimum Biopsy Site.

Direct immunofluorescence is a vital diagnostic test for assessing vesiculobullous disorders, vasculitides, and connective tissue diseases. It is a robust and valuable technique that offers essential diagnostic information for many critical dermatoses. Dermatopathologists depend heavily on the data obtained from direct immunofluorescence evaluation to confirm final diagnoses. Selecting the most appropriate biopsy site is necessary for maximizing diagnostic accuracy, and the best site may vary depending on the clinical differential diagnosis. Inaccurate biopsy site selection can significantly impact the accuracy of the results. To optimize the use of direct immunofluorescence studies, this review provides helpful guidelines and some practical tips for selecting the best biopsy site.

Neutralizing antibodies evolve to exploit vulnerable sites in the HCV envelope glycoprotein E2 and mediate spontaneous clearance of infection.

Individuals who clear primary hepatitis C virus (HCV) infections clear subsequent reinfections more than 80% of the time, but the mechanisms are poorly defined. Here, we used HCV variants and plasma from individuals with repeated clearance to characterize longitudinal changes in envelope glycoprotein E2 sequences, function, and neutralizing antibody (NAb) resistance. Clearance of infection was associated with early selection of viruses with NAb resistance substitutions that also reduced E2 binding to CD81, the primary HCV receptor. Later, peri-clearance plasma samples regained neutralizing capacity against these variants. We identified a subset of broadly NAbs (bNAbs) for which these loss-of-fitness substitutions conferred resistance to unmutated bNAb ancestors but increased sensitivity to mature bNAbs. These data demonstrate a mechanism by which neutralizing antibodies contribute to repeated immune-mediated HCV clearance, identifying specific bNAbs that exploit fundamental vulnerabilities in E2. The induction of bNAbs with these specificities should be a goal of HCV vaccine development.

Hysteresis and Its Correlation to Ionic Defects in Perovskite Solar Cells.

Ion migration has been reported to be one of the main reasons for hysteresis in the current-voltage (J-V) characteristics of perovskite solar cells. We investigate the interplay between ionic conduction and hysteresis types by studying Cs0.05(FA0.83MA0.17)0.95Pb(I0.9Br0.1)3 triple-cation perovskite solar cells through a combination of impedance spectroscopy (IS) and sweep-rate-dependent J-V curves. By comparing polycrystalline devices to single-crystal MAPbI3 devices, we separate two defects, ß and γ, both originating from long-range ionic conduction in the bulk. Defect ß is associated with a dielectric relaxation, while the migration of γ is influenced by the perovskite/hole transport layer interface. These conduction types are the causes of different types of hysteresis in J-V curves. The accumulation of ionic defects at the transport layer is the dominant cause for observing tunnel-diode-like characteristics in the J-V curves. By comparing devices with interface modifications at the electron and hole transport layers, we discuss the species and polarity of involved defects.

Arteriovenous malformation with hair collar sign.

We report the case of a newborn who was noted at birth to have an occipital scalp nodule presenting with a hair collar sign (HCS). The nodule had enlarged since birth. An MRI revealed a soft tissue mass on the occipital scalp without deep extension or cranial bone involvement. A biopsy of the nodule led to a diagnosis of arteriovenous malformation (AVM). A vascular malformation with HCS has not been reported before in North America. This case highlights the complexity of diagnosing a lesion with a hair collar sign.

Driving Under the Influence: An Unusual Case of Basal Ganglia Stroke Misdiagnosed as Intoxication.

Traditionally, strokes are characterized by negative symptoms, including contralateral hemiparesis, facial paralysis, and sensory loss in the upper face and upper extremities. Strokes rarely cause movement disorders such as ballismus, a severe chorea characterized by brief, sudden dance-like movements. Early identification of non-traditional stroke symptoms and risk factors for cerebrovascular disease is vital in providing timely treatment and improving patient outcomes. Our case highlights an uncommon complication of stroke and the need to use advanced imaging modalities, including MRI, to identify brain lesions when other testing is negative. This report adds to the body of literature highlighting ballismus, a rare presentation of stroke, and the lessons learned from managing this case.

The outbreak of migratory goat's brucellosis in the Swat ecosystem of Khyber Pakhtunkhwa.

Brucellosis is a major threat to public health especially in developing countries including Pakistan. This study reveals the characterisation of Brucella species affecting humans and goats in the Swat region of Khyber Pakhtunkhwa, Pakistan. Blood samples were collected from shepherds and goats and analysed by Rose Bengal precipitation test (RBPT), standard plate agglutination test (SPAT), polymerase chain reaction (PCR) and Sanger sequencing of 16S rRNA gene. The findings of the study indicated 24% (36/150) and 11.3% (17/150) positivity for Brucella abortus and Brucella melitensis, respectively, in human samples. In samples of goats, 26.66% (40/150) were positive for B. abortus and 16.66% (25/150) samples were positive B. melitensis by SPAT. The species-specific PCR confirmed B. abortus in 24% (36/150) of human samples and 26.66% (17/150) of goat samples by targeting the IS711 locus. The remaining seropositive samples were confirmed as B. melitensis using IS711 M species-specific primer. The sequences of the amplified fragments of the 16S rRNA gene were blasted, and phylogenetic analysis revealed that Brucella species circulating in the Swat district were closely related to B. melitensis and B. abortus reported from India, China, Philippines, and the United States (US) showing the existence of the possible epidemiological linkage among the Brucella species. This study concluded that there was a higher prevalence of B. abortus (26.6%) in humans and goats compared to B. melitensis (16.6%). These results revealed that the Brucella species were circulating in both humans and goats in the study areas. The findings of the study concluded that B. abortus and B. melitensis were circulating in goats and shepherds with a higher prevalence of B. abortus than B. melitensis. Furthermore, the Brucella species identified in Swat were phylogenetically related to the Brucella species reported from India, China, Philippines and the US.Contribution: The proposed study covers the scope of the journal. The species of the genus Brucella affect both animals and shepherds. This study investigates the seroprevalence of brucellosis in shepherds and goats in different geographical areas in the Swat district. The phylogenetic analysis of the Brucella spp. identified in Swat showed close relationships to the Brucella species reported in India, China, Philippines and the US, which shows the possible epidemiological linkages between the Brucella spp.

Overlapping Hepatotoxicity and Colitis Associated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that are widely used for the management of many solid-organ and hematologic cancers. These agents work by inhibition of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death-1 (PD-1), and PD ligand 1 (PD-L1). Hyperactivation of immune system results in ICI-associated adverse events. Simultaneous hepatotoxicity and colitis associated with ICIs is rare and potentially overlooked, as clinical symptoms are often nonspecific. A 73-year-old man with metastatic squamous cell carcinoma presented six weeks after starting pembrolizumab with abdominal discomfort and diarrhea. Pembrolizumab therapy was held, and supportive therapy with antidiarrheals provided partial relief. After initial workup, ICI-associated hepatitis (ICIH) and ICI-related colitis (ICIC) were diagnosed. Colitis resolution required corticosteroids. This case illustrates the importance of high index of clinical suspensions for gastrointestinal and hepatic adverse events associated with ICIs, which may be overlooked and result in severe complications. While isolated ICIH and ICIC are well known adverse events, overlapping ICIH and ICIC is rare. Prompt recognition, cessation of the inciting agent, and initiation of early supportive therapy are essential. Treatment may require corticosteroids or mycophenolate mofetil.

Prodromal Symptoms in Patients Presenting With Myocardial Infarction.

Background Prodromal symptoms are warning signs of an impending acute myocardial infarction (AMI). However, they are often overlooked by both patients and primary clinicians, and little is known about them. Therefore, this study aims to assess the frequency and types of prodromal symptoms in patients with AMI. Methodology This descriptive cross-sectional study was conducted at a tertiary care cardiac center. Consecutive patients diagnosed with AMI within the last week were evaluated for prodromal symptoms. The prodromal symptoms included chest pain, chest heaviness, chest burning, palpitations, fatigue, sleep disturbance, shortness of breath (SOB), dizziness, anxiety, sudden heat or cold, back pain, and vomiting. Results In a sample of 242 patients, 79.6% were males, with a mean age of 54.7 ± 12.2 years, and 179 (74%) were diagnosed with ST-segment elevation myocardial infarction (STEMI). Among the participants, 142 (58.7%) showed no prodromal symptoms. Among those with prodromal symptoms, chest pain was the predominantly reported prodromal symptom with a frequency of 68%, followed by chest heaviness at 44%, palpitations at 42%, shortness of breath at 34%, and chest burning at 27%. Unusual fatigue in 23% and sleep disturbance in 22% of the patients were also reported. Conclusion The findings from this study revealed that prodromal symptoms were present in a significant proportion of acute myocardial infarction (MI) cases, with more than four in 10 patients reporting these early warning signs. The most commonly observed prodromal symptoms were chest pain, chest heaviness, palpitations, shortness of breath, and chest burning. The timely identification of these symptoms can help prevent infarction, thereby reducing the burden of heart failure and other related mortalities.

Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys.

Background: Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods: In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings: We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%-56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27-2.40) and symptomatic TB (OR 1.49, 95% CI 1.34-1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17-2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55-1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70-3.62) for subclinical TB and OR 1.43, 95% CI 0.59-3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0-85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation: Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB. Funding: None.

EUS-guided versus percutaneous liver biopsy: A prospective randomized clinical trial.

Background and Objectives: Prospective studies comparing EUS-guided liver biopsy (EUS-LB) to percutaneous LB (PC-LB) are scarce. We compared the efficacy and safety of EUS-LB with those of PC-LB in a prospective randomized clinical trial. Methods: Between 2020 and 2021, patients were enrolled and randomized (1:1 ratio). The primary outcome was defined as the proportion of patients with ≥11 complete portal tracts (CPTs). The sample size (n = 80) was calculated based on the assumption that 60% of those in the EUS-LB and 90% of those in the PC-LB group will have LB with ≥11 CPTs. The secondary outcomes included proportion of patients in whom a diagnosis was established, number of CPTs, pain severity (Numeric Rating Scale-Pain Intensity), duration of hospital stay, and adverse events. Results: Eighty patients were enrolled (median age, 53 years); 67.5% were female. Sixty percent of those in the EUS-LB and 75.0% of those in the PC-LB group met the primary outcome (P = 0.232). The median number of CPTs was higher in the PC-LB (17 vs 13; P = 0.031). The proportion of patients in whom a diagnosis was established was similar between the groups (92.5% [EUS-LB] vs 95.0% [PC-LB]; P = 1.0). Patients in the EUS-LB group had less pain severity (median Numeric Rating Scale-Pain Intensity, 2.0 vs 3.0; P = 0.003) and shorter hospital stay (2.0 vs 4.0 hours; P < 0.0001) compared with the PC-LB group. No patient experienced a serious adverse event. Conclusions: EUS-guided liver biopsy was safe, effective, better tolerated, and associated with a shorter hospital stay.