DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8.

Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits potent anti-inflammatory effects and attenuates disease symptoms in several animal models of arthritis. Transcriptomic and epigenomic profiling show that DAC-mediated hypomethylation regulates a wide range of cell types in arthritis, altering the differentiation trajectories of anti-inflammatory macrophage populations, regulatory T cells, and tissue-protective synovial fibroblasts (SFs). Mechanistically, DAC-mediated demethylation of intragenic 5'-Cytosine phosphate Guanine-3' (CpG) islands of the transcription factor Irf8 (interferon regulatory factor 8) induced its re-expression and promoted its repressor activity. As a result, DAC restored joint homeostasis by resetting the transcriptomic signature of negative regulators of inflammation in synovial macrophages (MerTK, Trem2, and Cx3cr1), TREGs (Foxp3), and SFs (Pdpn and Fapα). In conclusion, we found that Irf8 is necessary for the inhibitory effect of DAC in murine arthritis and that direct expression of Irf8 is sufficient to significantly mitigate arthritis.

Malaria in pregnancy: Meta-analyses of prevalence and associated complications.

This review aims to assess the prevalence of malaria in pregnancy during antenatal visits and delivery, species-specific burden together with regional variation in the burden of disease. It also aims to estimate the proportions of adverse pregnancy outcomes in malaria-positive women. Based on the PRISMA guidelines, a thorough and systematic search was conducted in July 2023 across two electronic databases (including PubMed and CENTRAL). Forest plots were constructed for each outcome of interest highlighting the effect measure, confidence interval, sample size, and its associated weightage. All the statistical meta-analysis were conducted using R-Studio version 2022.07. Sensitivity analyses, publication bias assessment, and meta-regression analyses were also performed to ensure robustness of the review. According to the pooled estimates of 253 studies, the overall prevalence of malaria was 18.95% (95% CI: 16.95-21.11), during antenatal visits was 20.09% (95% CI: 17.43-23.06), and at delivery was 17.32% (95% CI: 14.47-20.61). The highest proportion of malarial infection was observed in Africa approximating 21.50% (95% CI: 18.52-24.81) during ANC and 20.41% (95% CI: 17.04-24.24) at the time of delivery. Our analysis also revealed that the odds of having anaemia were 2.40 times (95% CI: 1.87-3.06), having low birthweight were 1.99 times (95% CI: 1.60-2.48), having preterm birth were 1.65 times (95% CI: 1.29-2.10), and having stillbirths were 1.40 times (95% CI: 1.15-1.71) in pregnant women with malaria.

Assessing the health consequences of indoor air pollution from biomass fuel combustion on pediatric populations in rural communities of Pakistan.

Indoor air pollution arising from burning of biomass fuels poses a significant threat to child health in rural areas of Pakistan. This cross-sectional study aimed to assess health implications associated with indoor air pollution resulting from biomass burning among children under 12 years of age in rural Punjab. A questionnaire-based survey was conducted in six randomly selected rural districts of Punjab, characterized by their primary reliance on biomass fuels. The findings revealed that several characteristics, such as monthly household income, number of living rooms, secondary use of solid fuels, kitchen type, type of cooking stove, and presence of child in the kitchen with their mother, exhibited significant associations (p < 0.05) with negative health impacts among children. Reported health effects among the children included coughing (18.7%), watery eyes (17.7%), eye irritation (12.3%), runny nose (11.8%), breathing difficulties (8.5%), phlegm (38%), headache (25%), nausea (20.1%), dizziness (6.7%), asthma (6.4%), tuberculosis (1.8%), and pneumonia (1.5%).

Grade of Primary Cutaneous Leiomyosarcoma Dictates Risk for Metastatic Spread and Disease-Specific Mortality.

BACKGROUND AND OBJECTIVES: Primary cutaneous leiomyosarcoma (cLMS), a rare, typically intradermal tumor, has previously been reported to exhibit an indolent course of disease with zero-to-low risk of local recurrence or distant metastasis. This study seeks to evaluate recurrence and survival of cLMS patients through study of its clinicopathologic and treatment characteristics. METHODS: All patients included underwent resection of primary cLMS at this institution between 2006 and 2019. A retrospective cohort study analysis of clinicopathologic characteristics, treatment, recurrence, and overall survival was performed. Data was assessed through descriptive statistics and outcome measures assessed by Cox proportional models and log-rank tests. RESULTS: Eighty-eight patients with cLMS were evaluated. The majority were men (n = 68, 77%) and Caucasian (n = 85, 97%), with median age at diagnosis of 66 years (range 20-96). 65% of tumors were located on the extremities, with a median size of 1.3 cm (range .3-15). Assessment revealed low (n = 41, 47%), intermediate (n = 29, 33%), and high (n = 18, 20%) grade tumors, demonstrating extension into subcutaneous tissue in 38/60 (60%), with 3 patients exhibiting extension into muscle (3%). All underwent resection as primary treatment with median 1 cm margins (range .5-2). With median follow-up of 27.5 months (IQR 8-51; range 1-131), no low-grade cases had recurrence or death while there was a recurrence rate of 19.1% (9/47) and death rate of 8.5% (4/47) in intermediate- to high-grade cases. CONCLUSIONS: Primary tumor resection of cLMS provides excellent local control for low-grade tumors as no low-grade cases experienced recurrence. For patients with intermediate- to high-grade tumors, there is potential for local recurrence, distant metastasis, and death, and therefore surveillance following treatment is encouraged.

Antibiotic Prophylaxis for Upper Gastrointestinal Bleed in Liver Cirrhosis; Less May Be More.

INTRODUCTION: Administration of antibiotics in patients with cirrhosis and upper gastrointestinal bleeding has been shown to improve outcomes. Little is known regarding optimum duration of prophylactic antibiotics. Seven days of antibiotics are generally recommended but very few studies have compared antibiotic duration to clinical outcomes in current available scientific literature. The goal of our study was to study the effect of shorter antibiotic duration on patient outcomes. METHODS: We conducted a retrospective cohort study of patients with cirrhosis presenting with upper GI bleeding at our institute from 2010 to 2018. Patients were divided into three cohorts based on duration of antibiotic administration for prophylaxis: 1-3 days of antibiotics, 4-6 days of antibiotics and 7 days or more of antibiotics. Rates of infection diagnosis within 30 days, rebleeding, and mortality were compared between the three groups with Chi square, Fisher Exact and Kruskall-Wallace tests. Multivariable analysis was conducted to evaluate independent risk factors for infection. RESULTS: Medical charts of 980 patients with cirrhosis and upper GI bleeding during the study period were reviewed. A total of 303 with upper gastrointestinal bleeding were included in the final sample, of these 243 patients received antibiotics for prophylaxis and were included for analysis. Seventy-seven patients received antibiotic therapy for 3 days or less, 69 patients for 4-6 days, and 97 patients longer than 6 days. The three groups were well matched in demographic and clinical variables. Twenty-seven patients developed infections within 30 days of bleeding. MELD-Na score at presentation and presence of ascites were associated with infection within 30 days. Rates of infection were not statistically different between the three antibiotic groups (p = 0.78). In the thirty days following the GI bleed, pneumonia was the most diagnosed infection (eleven patients) followed by urinary tract infections (eight patients). Four patients developed spontaneous bacterial peritonitis and three were diagnosed with bacteremia. There was no difference in time to infection (Kruskall Wallace test p = 0.75), early re-bleeding (p = 0.81), late re-bleeding (p = 0.37) and in-hospital mortality (p = 0.94) in the three groups. Six patients in the cohort developed C. Difficile infection; no patient in the short antibiotic group developed C. Difficile infection. CONCLUSION: Short course of antibiotics for prophylaxis (3 days) appears safe and adequate for prophylaxis in patients with cirrhosis with upper gastrointestinal bleeding if there is no active infection.

Self-expanding metal stents for the treatment of malignant colon obstruction from extra-colonic malignancy versus intra-colonic malignancy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The relative utility of self-expanding metal stent (SEMS) insertion for malignant colon obstruction (MCO) due to extra-colonic malignancy (ECM) versus intra-colonic malignancy (ICM) is understudied. METHODS: A systematic search was done from inception-April 2021 to identify reports of safety and efficacy of SEMS insertion for the treatment of MCO-ECM versus MCO-ICM. A meta-analysis of proportions, comparative meta-analysis to compute relative risks (RR), and mean differences (MD) was performed. Subgroup analyses and influence analyses were conducted. The certainty in estimates of effect(s) was assessed using the GRADE approach. RESULTS: Eight non-randomized studies were identified; 46% (39-53%) and 63% (59-67%) of patients in the ECM and ICM groups were male. Most obstructions were in the rectosigmoid colon in both ECM and ICM groups. SEMS insertion in MCO-ECM was associated with an increased risk of technical failure compared to MCO-ICM (RR 2.92; 1.13-7.54; Certainty: Very Low). Risk of clinical failure of SEMS was higher in MCO-ECM compared to MCO-ICM (RR 2.88; 1.58-2.52; Certainty: Very Low). The risk of clinical failure remained significant throughout the influence analysis, as well as on subgroup analysis. There was no significant difference in the risk of adverse events or luminal perforation with SEMS insertion among patients with MCO-ECM and MCO-ICM. On influence analysis, removal of one study unveiled a significant increase in the risk of luminal perforation in MCO-ECM (RR 3.22; 1.44-7.19; p = 0.004). CONCLUSION: SEMS for MCO-ECM may have a technical success rate comparable to or questionably worse than MCO-ICM, with low certainty in estimate of effects. SEMS deployment in MCO-ECM carries a higher risk of clinical failure, with a questionably higher risk of luminal perforation.

Youth engagement in mental health research: A systematic review.

INTRODUCTION: Patient engagement in youth mental health research has the potential to inform research on the interventions, services and policies that will benefit youth. At present, there is little evidence to guide mental health researchers on youth engagement. This systematic review aims to describe the impacts of youth engagement on mental health research and to summarize youth engagement in mental health research. METHODS: We searched the following databases: MEDLINE, EMBASE and PsycINFO, using a combination of subject headings, keywords and synonyms for the concepts 'patient engagement', 'youth' and 'mental health'. Articles that described engaging youth in mental health research were included. Two reviewers performed the study selection. Study characteristics, research activities performed by youth, impacts of youth engagement, challenges, and facilitators to engagement and recommendations for youth engagement described by authors were extracted. Quality appraisal involved determining the level of engagement of youth and the stage(s) of research where youth were involved. RESULTS: The database search returned 2836 citations, 151 full-text articles were screened and 16 articles, representing 14 studies, were selected for inclusion. Youth were involved at nearly all stages of the research cycle, in either advisory or co-production roles. Youth engagement impacts included enhancing relevant research findings, data collection and analysis and dissemination to academic and stakeholder audiences. Both youth and academic researchers reported personal development across many domains. One negative impact reported was the increase in funding and resources needed for engagement. We produced a list of 35 recommendations under the headings of training, youth researcher composition, strategy, expectations, relationships, meeting approaches and engagement conditions. CONCLUSIONS: This study provides an understanding of the impacts and recommendations of youth engagement in mental health research. The findings from this study may encourage researchers to engage youth in their mental health research and support youth engagement in funding applications. PATIENT AND PUBLIC CONTRIBUTION: We consulted three youths with experience being engaged in mental health research about the review findings and the discussion. One youth designed a visual representation of the results and provided feedback on the manuscript. All youth's input informed the way the findings were presented and the focus of the discussion.

A Low-Profile Antenna for On-Body and Off-Body Applications in the Lower and Upper ISM and WLAN Bands.

The article presents a Co-planar Waveguide (CPW) fed antenna of a low-profile, simple geometry, and compact size operating at the dual band for ISM and WLAN applications for 5G communication devices. The antenna has a small size of 30 mm × 18 mm × 0.79 mm and is realized using Rogers RT/Duroid 5880 substrate. The proposed dual-band antenna contains a CPW feedline along with the triangular patch. Later on, various stubs are loaded to obtain optimal results. The proposed antenna offers a dual band at 2.4 and 5.4 GHz while covering the impedance bandwidths of 2.25-2.8 GHz for ISM and 5.45-5.65 GHz for WLAN applications, respectively. The proposed antenna design is studied and analyzed using the Electromagnetic (EM) High-Frequency Structure Simulator (HFSSv9) tool, and a hardware prototype is fabricated to verify the simulated results. As the antenna is intended for on-body applications, therefore, Specific Absorption Rate (SAR) analysis is carried out to investigate the Electromagnetic effects of the antenna on the human body. Moreover, a comparison between the proposed dual-band antenna and other relevant works in the literature is presented. The results and comparison of the proposed work with other literary works validate that the proposed dual-band antenna is suitable for future 5G devices working in Industrial, Scientific, Medical (ISM), and Wireless Local Area Network (WLAN) bands.

Homozygous Mutations in Thyroid Peroxidase (TPO) in Hypothyroidism with Intellectual Disability, Developmental Delay, and Hearing and Ocular Anomalies in Two Families: Severe Manifestation of Untreated TPO-deficiency Poses a Diagnostic Dilemma.

Intellectual disability (ID) involves compromised intellectual, learning and cognitive skills, and behavioral capabilities with reduced psychomotor skills. One of the preventable causes of ID is congenital hypothyroidism (CH), which may be due to biallelic mutations in thyroid peroxidase (TPO). In low- and middle-income countries with no newborn screening programs, CH poses a great risk of ID and long-term morbidity. We report two large Pakistani families with a total of 16 patients afflicted with CH. Detailed clinical and behavioral assessments, SNP-based homozygosity mapping, linkage analysis, and exome sequencing were performed. Initially, affected individuals were referred as suffering ID (in 11 of 16 patients) and developmental delay (in 14). Secondary/associated features were verbal apraxia (in 13), goiter (in 12), short stature (in 11), limb hypotonia (in 14), no pubertal onset (five of 10 of age ≥14 years), high myopia (in eight), muscle cramps (in six), and in some, variable microcephaly and enuresis/encopresis, fits, chronic fatigue, and other behavioral symptoms, which are not characteristics of CH. Molecular genetic analyses led to the discovery of homozygous variants in TPO: novel missense variant c.719A>G (p.Asp240Gly) in family 1 and rare c.2315A>G (p.Tyr772Cys) in family 2. In low-resource countries where neonatal screening programs do not include a CH test, the burden of neurodevelopmental disorders is likely to be increased due to untreated CH. Secondly, in the background of the high prevalence of recessive disorders due to high parental consanguinity, the severe manifestation of TPO-deficiency mimics a wide range of neurological and other presentations posing a diagnostic dilemma.

Survival in general surgery: The female surgeons' perspective.

Objective: Specialty choices in health profession has long been influenced by gender. The field of General Surgery remains the least preferred specialty by females, especially in Pakistan. The objective of this study was to identify the factors leading to success and retention of females in General Surgery in Pakistan. Methods: Qualitative case study was conducted from February to May 2020 at Khyber Medical University, Peshawar. Ten semi-structured interviews were conducted with purposive sample of female surgeons at various academic position in different tertiary care hospitals of Pakistan. Data were thematically analyzed. Results: Participants were driven by their passion for surgery, which led them to choose this specialty in the beginning. Their survival in male dominant workplace was made possible by their own personality traits and conducive environment provided by the supervisors and peers. However, a structured mentorship program for females was found lacking. Conclusion: The necessary ingredients for success are passion and personality traits in any field but attention to nurturing and supportive environment for females in the General Surgery is paramount in determining success. Due consideration to the factors identified in the current study will enhance the retention and success of females in General Surgery.

Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Locoregional Melanoma After Failure of Immunotherapy: An International Multi-Institutional Experience.

BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma. METHODS: An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed. RESULTS: Of 112 patients, median age at T-VEC initiation was 69 years (range 21-93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE). CONCLUSIONS: T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response.

Sensitive and highly selective colorimetric biosensing of vitamin-C and vitamin-B1 by flavoring agent-based silver nanoparticles.

A sensitive scheme was established for the detection of vitamin C (Ascorbic acid) and vitamin B1 (Thiamin HCl) using Maltol capped AgNPs (McAgNPs) as colorimetric sensor. The designed scheme showed an instant alteration in color from yellow to orange and green for vitamin-C and vitamin B1 sequentially. The probe was sensitive in a concentration range of (0-1 µM) with limit of detection 0.064 and 0.038 µM for vitamin C and vitamin B1 sequentially. The interaction mechanism between vitamin C and vitamin B1 and McAgNPs was evaluated by visible spectroscopy, FTIR, and AFM. Vitamin C attaches on the surface of nanoparticles by C=O group, while OH, C-S-C, and NH2 groups are involved in the binding of vitamin B1 with McAgNPs. The Vit-C/Vit-B1-McAgNPs complexes were stable over a wide range of pHs. The size of McAgNPs increased after the interaction of vitamin C/vitamin B1 from 30-40 nm to 500 and 400 nm sequentially. The scheme was successfully applied for the detection of vitamin C and vitamin B1 in urine, plasma, water, and commercial pharmaceutical tablets with good recoveries. The scheme was ascertained to be more sensitive than many other formerly described schemes.

Addressing rural health disparity with a novel hospital sleep apnea screening: Precision of a high-resolution pulse oximeter in screening for sleep-disordered breathing.

PURPOSE: High-resolution pulse oximetry (HRPO) may offer a low-cost and simple screening option for sleep-disordered breathing (SDB) that could be vitally important in rural areas with limited healthcare resources and specialty care. Our team hypothesized that application of this technology to a broad cohort of rural dwelling hospitalized individuals would demonstrate congruence similar to previous urban studies comparing HRPO to portable sleep monitors. METHODS: This retrospective study was conducted at West Virginia University Hospital and compared indices obtained from HRPO with those obtained from a type III portable sleep monitor (PM) on the same night. RESULTS: A total of 365 individuals underwent evaluation. The mean oxygen desaturation index (18.8 ± 19.3 events/h) from the HRPO was slightly higher than the mean respiratory event index (16.0 ± 18.1 events/h, p ≤ 0.001) from the PM. ROC curves were developed for thresholds of apnea severity predicted by the screening program. The AUC values for all three thresholds exceeded 0.92 and for a respiratory event index (REI) of ≥ 30 was 0.965. Indices from the PM and HRPO demonstrated agreement in those individuals with screening suggestive of moderate to severe disease. CONCLUSION: This study demonstrates that use of HRPO in screening for SDB in hospitalized patients from rural communities is as accurate as PM and may serve as a simple cost-effective tool to address sleep health disparities in these regions with significant health inequity. Our data extend previous findings by applying HRPO to a larger hospitalized cohort with highly prevalent cardiopulmonary disease.

A Conformal Frequency Reconfigurable Antenna with Multiband and Wideband Characteristics.

A compact flexible multi-frequency antenna for smart portable and flexible devices is presented. The antenna consists of a coplanar waveguide-fed slotted circular patch connected to a rectangular secondary resonator (stub). A thin low-loss substrate is used for flexibility, and a rectangular stub in the feedline is deployed to attain wide operational bandwidth. A rectangular slot is etched in the middle of the circular patch, and a p-i-n diode is placed at its center. The frequency reconfigurability is achieved through switching the diode that distributes the current by changing the antenna's electrical length. For the ON state, the antenna operates in the UWB region for -10 dB impedance bandwidth from 2.76 to 8.21 GHz. For the OFF state of the diode, the antenna operates at the ISM band (2.45/5.8 GHz), WLAN band (5.2 GHz), and lower X-band (8 GHz) with a minimum gain of 2.49 dBi and a maximum gain of 5.8 dBi at the 8 GHz band. Moreover, the antenna retains its performance in various bending conditions. The proposed antenna is suitable for modern miniaturized wireless electronic devices such as wearables, health monitoring sensors, mobile Internet devices, and laptops that operate at multiple frequency bands.

Cerebral Folate Metabolism in Post-Mortem Alzheimer's Disease Tissues: A Small Cohort Study.

We investigated the cerebral folate system in post-mortem brains and matched cerebrospinal fluid (CSF) samples from subjects with definite Alzheimer's disease (AD) (n = 21) and neuropathologically normal brains (n = 21) using immunohistochemistry, Western blot and dot blot. In AD the CSF showed a significant decrease in 10-formyl tetrahydrofolate dehydrogenase (FDH), a critical folate binding protein and enzyme in the CSF, as well as in the main folate transporter, folate receptor alpha (FRα) and folate. In tissue, we found a switch in the pathway of folate supply to the cerebral cortex in AD compared to neurologically normal brains. FRα switched from entry through FDH-positive astrocytes in normal, to entry through glial fibrillary acidic protein (GFAP)-positive astrocytes in the AD cortex. Moreover, this switch correlated with an apparent change in metabolic direction to hypermethylation of neurons in AD. Our data suggest that the reduction in FDH in CSF prohibits FRα-folate entry via FDH-positive astrocytes and promotes entry through the GFAP pathway directly to neurons for hypermethylation. This data may explain some of the cognitive decline not attributable to the loss of neurons alone and presents a target for potential treatment.

Burden of Congenital and Hereditary Anomalies in Hazara Population of Khyber Pakhtunkhwa, Pakistan.

Background and Objectives: In Pakistan, there is high incidence of congenital and hereditary anomalies (CA) which are a leading cause of infant mortality and morbidity. In order to elucidate the burden and biodemographic correlates of CA, this study was aimed to report the prevalence-pattern and phenotypic attributes of CA in the Hazara population of Khyber Pakhtunkhwa, Pakistan. Methods: In a retrospective cross-sectional study, subjects/families with CA were recruited from district hospitals and community centers. Phenotypic and descriptive data were obtained; pedigrees were analyzed and parental and biodemographic attributes were recorded. Results: A total of 1,189 independent subjects and/or families with CA were ascertained. The malformations were grouped into nine major and 95 minor categories. Neurological disorder had the highest representation (n=486; proportion=0.409; 95% CI=0.381-0.437), followed by limb defects (n=292; proportion=0.246, 95% CI=0.221-0.270), musculoskeletal defects, sensorineural/ear defects, blood disorders, eye/visual impairments, ectodermal anomalies, and congenital heart defects. In this cohort, sporadic cases were 65% and familial 35%. Parental consanguinity was significantly higher in isolated cases compared to syndromic, and in familial cases compared to sporadic. Further, speech apraxia and epilepsy were most common associations among the syndromic cases. The assessment of variables like demography, parental consanguinity, familial/sporadic nature, and pedigree structures showed conspicuous heterogeneity among the major and minor categories of CA. Conclusions: The trend of CA and high incidence of sporadic cases observed in this cohort indicate that nongenetic factors may play a significant role in their etiology which could be minimized by improving the healthcare system.

Active surveillance of patients who have sentinel node positive melanoma: An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT-2).

BACKGROUND: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. METHODS: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. CONCLUSIONS: Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. LAY SUMMARY: For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

Concerns and psychological well-being of healthcare workers during the COVID-19 pandemic in a tertiary care hospital in New South Wales.

BACKGROUND: In early 2020, the impending COVID-19 pandemic placed a once-in-a-generation professional and personal challenge on healthcare workers. Publications on direct physical disease abound. The authors wanted to focus on doctors' psychological well-being. AIMS: To assess the impact of the COVID-19 pandemic on doctors' well-being and evaluate their concerns as the pandemic progressed. METHODS: A mixed-methods, hospital-based survey was sent to doctors at the 650-bed tertiary referral hospital in NSW at two different periods (late-March and early May 2020). A validated mental well-being tool (Short Warwick Edinburgh Mental Well-being Scale (SWEMWBS)) was combined with COVID-19-specific questions. RESULTS: Two hundred and thirty-five responses were obtained from 450 doctors, with a response rate of 32% in the first survey and 20% in the second. The majority (35%) of respondents were doctors-in-training, followed by staff-specialists (23%). The highest response was from frontline workers in both surveys, including the intensive care unit (27%), anaesthesia (21%) and emergency department (13%). 'Extreme concern' regarding personal protective equipment (PPE) shortage dropped from 22.6% to 2.2% and 'extreme concern' of contracting COVID-19 fell from 22.6% to 3.4% in the second survey. The proportion of respondents with a 'low' psychological well-being score improved from 38% to 27% between the two surveys. The resulting mean improvement in the SWEMWBS was 3.49 (95% confidence interval = 3.06-3.91, P < 0.001). CONCLUSION: Both COVID-19 specific concerns and psychological well-being improved greatly in the second survey. Possible explanations are the fall in COVID-19 cases in the district, improvements in PPE supply and supportive measures communicated to doctors during this period.

Recurrent formation of haematocolpos in a young girl with multiple congenital anomalies of the urogenital tract.

An 11-year-old girl, a known case of left crossed fused renal ectopia and sacral hypoplasia presented to the gynaecological OPD in Karachi, Pakistan, in February 2019 with complaints of abdominal pain. On examination, she was found to have a septum covering her vaginal orifice. She was subsequently diagnosed with haematocolpos secondary to imperforate hymen. Incision and drainage was done. However, despite surgical management, she continued to have recurrent formation of haematocolpos for the next two months secondary to multiple complete and partial transverse vaginal septa and post-operative formation of adhesions. Definitive management was done with ultrasound guided needle puncture and drainage, followed by post-operative tampon use to maintain patency.

Prevalence of EBV, CMV, and HPV in oral squamous cell carcinoma patients in the Pakistani population.

Many studies have proposed an important role of viruses in the pathogenesis of oral cancer. The present study aimed to find out the prevalence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human papillomavirus (HPV) among patients with oral squamous cell carcinoma (OSCC) in a Pakistani cohort. We investigated tissue samples obtained from 58 patients with OSCC using the polymerase chain reaction assay. No sample was positive for HPV. EBV was identified in 15 patients (25.86%), and CMV in three patients (5.17%). Coinfection with one or more viruses was detected in two cases and was coinfection with EBV and CMV. These results suggest a low prevalence of these viruses in OSCC patients in the Pakistani population compared to most other countries where the prevalence of these viruses has been reported in the past. Nevertheless, further studies are necessary to determine the potential role of EBV and the possible importance of CMV as an infection cofactor in oral cancer.