The prevalence and risk factors of methicillin-resistant Staphylococcus aureus among pediatric populations: a systematic review and meta-analysis.

There is scarcity in the data about MRSA prevalence and risk factors among the pediatric population. This research explores the global prevalence and risk factors of MRSA among the pediatric population. PubMed, Scopus, Web of Sciences, and the Cochrane Central Register of Controlled Trials were systematically searched. Our primary goal was to assess the prevalence of MRSA colonization and its related risk factors in the general pediatric population. A total of 124 studies encompassing 44 million participants were included in this meta-analysis, and the overall pooled estimated global prevalence of MRSA colonization in pediatric was 5% [95% CI 4-5%]. Female sex (OR = 4.17; 95% CI, 3.31-5.27), recent surgery (OR = 3.79; 95% CI, 2.20-6.52), recent hospitalization (OR = 2.63; 95% CI, 1.78-3.86), and antibiotic use (OR = 2.42; 95% CI, 1.58-3.72) were significantly associated with higher odds of MRSA colonization. CONCLUSION: Future research should build on these findings by emphasizing ongoing efforts to combat MRSA in pediatric settings and implementing targeted interventions. WHAT IS KNOWN: • Methicillin-resistant Staphylococcus aureus (MRSA) is considered a threat to public health. It is noteworthy to mention that the prevalence of MRSA strains has not been adequately quantified in many countries, especially in the pediatric population. The pediatric population is a pivotal source of MRSA and may play a central role in its distribution in both community and healthcare settings. A notable study underscores the gravity of the situation, estimating a tenfold increase in the incidence of MRSA infection among children in the USA between 1999 and 2008. WHAT IS NEW: • Here we present the first global systematic review and meta-analysis to investigate the prevalence and risk factors of MRSA among the pediatric population. A total of 124 studies encompassing 44 million participants were included in this analysis. The overall pooled estimated global prevalence of MRSA colonization in the pediatric population was 5% [95% CI 4-5%]. The prevalence was the highest in Asia and lowest in Europe. Female sex, recent surgery, recent hospitalization, and antibiotic use were significantly associated with higher odds of MRSA colonization.

Risk Factors of Obstructive Sleep Apnea (OSA) in Pediatric Patients: A Systematic Review and Meta-analysis.

INTRODUCTION: This review aimed to assess the risk factors of Obstructive Sleep Apnea (OSA) in pediatric children, a common condition with serious long-term sequela. METHODS: PubMed, CENTRAL, Scopus, and Google Scholar were searched using the keywords "Apnea", "Obstructive Sleep" OR "Obstructive Sleep Apnea Syndrome" AND "Child" OR "Children" OR "Pediatrics". Data from 35 studies involving 497,688 pediatric patients diagnosed with OSA using polysomnography were reviewed. Risk factors examined included sex, obesity, neck circumference, tonsillar/adenoid hypertrophy, respiratory infections, nasal stenosis, parental OSA/smoking, ethnicity, preterm birth, and breastfeeding history. Relative Risk (RR) with 95% Confidence Intervals (95% CI) were calculated, using Cochrane Q and I² statistics to estimate heterogeneity. RESULTS: Tonsillar hypertrophy (RR = 3.55), adenoid hypertrophy (RR = 1.63), respiratory tract infection (RR = 2.59), obesity (RR = 1.74), and family history of OSA (RR = 3.03) were significantly associated with pediatric OSA. White ethnicity was protective (RR = 0.77). DISCUSSION: Recognizing these risk factors aids in early diagnosis and treatment of pediatric OSA.

Brace-related Stress and Quality of Life Parameters between Chêneau and Boston Braces: A Cross-sectional Comparative Study on Adolescent Idiopathic Scoliosis in Saudi Arabia.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is the most prevalent spinal deformity affecting healthy children. Although AIS typically lacks symptomatic manifestations, its resultant deformities can affect patients' quality of life (QoL). Evaluating QoL and stress levels is crucial in determining the optimal brace type for AIS patients; however, research comparing the effectiveness of different brace types in this regard is lacking. Therefore, this study aimed to evaluate the impact of Boston versus Chêneau braces on QoL and stress levels in AIS patients. METHODS: This cross-sectional study was conducted at a medical institution in Riyadh, Saudi Arabia, involving 52 eligible patients selected through stratified random sampling based on type of brace as the main stratum. The inclusion criteria were idiopathic scoliosis, age ≥ 10 years, bracing for at least 3 months, and no history of cancer. QoL was evaluated according to the revised Scoliosis Research Society 22-item questionnaire (SRS-22r) and stress levels according to the eight-item Bad Sobernheim stress questionnaire (BSSQ-Brace). Independent-sample t-tests were used to compare brace-related QoL and stress level according to participants' sex and brace type. RESULTS: Overall, 32 participants were treated with Boston braces (seven men and 25 women), with a median (IQR) age of 11.00 years (10.00-13.00), and 20 participants were treated with Chêneau braces (three men, 17 women), with a median (IQR) age of 12.50 years (10.00-14.25). The total SRS-22 score was not significantly different between the brace groups (p = 0.158). However, patients in the Boston brace group reported significantly higher satisfaction levels (median = 4.00, IQR = 3.50-4.50) than did those in the Chêneau brace group (median = 3.25, IQR = 2.38-4.13, p = 0.013, moderate effect size = 0.345, 95% CI = 0.060 to 0.590). Furthermore, the BSSQ-brace total score was significantly higher in the Boston brace group (median = 9.00, IQR = 8.00-12.00) than in the Chêneau brace group (median = 7.50, IQR = 4.75-10.00, p = 0.007, moderate effect size = 0.376, 95% CI = 0.130 to 0.590), indicating higher stress levels in the Chêneau brace group. CONCLUSION: The QoL in AIS patients undergoing brace treatment was comparable across groups. Nonetheless, patients who used Chêneau braces experienced higher stress levels and lower treatment satisfaction rates than did those who used Boston braces. These findings can inform clinical decisions regarding prescription of bracing types and highlight the need for further in-depth research.

The Tumor Microbiome Reacts to Hypoxia and Can Influence Response to Radiation Treatment in Colorectal Cancer.

Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation's ability to kill cells. We hypothesized that some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. Therefore, we examined the RNA sequencing data from the Oncology Research Information Exchange Network database of patients with colorectal cancer treated with radiotherapy. We identified microbial RNAs for each tumor and related them to the hypoxic gene expression scores calculated from host mRNA. Our analysis showed that the hypoxia expression score predicted poor patient outcomes and identified tumors enriched with certain microbes such as Fusobacterium nucleatum. The presence of other microbes, such as Fusobacterium canifelinum, predicted poor patient outcomes, suggesting a potential interaction between hypoxia, the microbiome, and radiation response. To experimentally investigate this concept, we implanted CT26 colorectal cancer cells into immune-competent BALB/c and immune-deficient athymic nude mice. After growth, in which tumors passively acquired microbes from the gastrointestinal tract, we harvested tumors, extracted nucleic acids, and sequenced host and microbial RNAs. We stratified tumors based on their hypoxia score and performed a metatranscriptomic analysis of microbial gene expression. In addition to hypoxia-tropic and -phobic microbial populations, analysis of microbial gene expression at the strain level showed expression differences based on the hypoxia score. Thus, hypoxia gene expression scores seem to associate with different microbial populations and elicit an adaptive transcriptional response in intratumoral microbes, potentially influencing clinical outcomes. SIGNIFICANCE: Tumor hypoxia reduces radiotherapy efficacy. In this study, we explored whether some of the clinical effects of hypoxia could be due to interaction with the tumor microbiome. Hypoxic gene expression scores associated with certain microbes and elicited an adaptive transcriptional response in others that could contribute to poor clinical outcomes.

Patient reported outcomes and patient experiences of immune checkpoint modulators for advanced or recurrent melanoma: a mixed methods study.

PURPOSE: Little is known about late and long-term patient-reported outcomes (PROs) of immune checkpoint modulators (ICMs) outside clinical trials. We conducted a cross-sectional, mixed-methods study to describe long-term PROs among advanced melanoma patients who began standard of care treatment with ICMs at least 1 year previously. METHODS: All participants completed the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM), assessing 46 immune-related side effects on a 5-point Likert scale, and a subset completed individual interviews. Descriptive statistics were computed for quantitative data and applied thematic analysis was used to examine qualitative data. RESULTS: Participants (N = 80) had a mean age of 67 years, and the majority were male (66%), non-Hispanic White (96%), and college graduates (61%). Single-agent nivolumab was the most common first (47%) and current/recent ICM (64%). On the FACT-ICM, 98% of participants reported at least one side effect, and 78% reported moderate or severe side effects. The most common moderate or severe side effects were aching joints (43%) and fatigue (38%). In interviews (n = 20), we identified five themes regarding patients' longer-term experiences after ICMs: lasting fatigue or decline in functioning, minimal side effects, manageable thyroid and pituitary dysfunction, skin conditions can be difficult to manage, and treating the cancer is worth the side effects. CONCLUSIONS: Nearly all patients reported side effects of ICMs at least 1 year after starting treatment. Our findings suggest that ICM side effect screening and management-especially for aching joints and fatigue-are indicated during long-term care of people living with advanced melanoma.

Modified 5-Item Frailty Index: A Useful Tool for Assessing the Impact of Frailty on Postoperative Morbidity and Mortality Following Surgical Fixation of Thoracolumbar Fractures.

OBJECTIVES: The modified 5-item frailty index (mFI-5) is a comorbidity-based risk stratification tool to predict adverse events following various neurologic surgeries. This study aims to quantify the association between increased mFI-5 and postoperative complications and mortality following surgical fixation of traumatic thoracolumbar fractures. METHODS: The 2011-2021 American College of Surgeons - National Surgical Quality Improvement Program (ACS-NSQIP) dataset was used to identify patients undergoing fusion surgeries for thoracolumbar spine fractures. The mFI-5 score was calculated based on the presence of 5 major comorbidities: congestive heart failure within 30 days before surgery, insulin-dependent or noninsulin-dependent diabetes mellitus, chronic obstructive pulmonary disease, partially dependent or totally dependent functional health status at the time of surgery, and hypertension requiring medication. Multivariate analysis assessed the independent impact of increasing mFI-5 scores on postoperative 30-day morbidity and mortality while controlling for baseline clinical characteristics. RESULTS: A total of 66,904 patients were included in our analysis (54.2% female, mean age 62.27 ± 12.93 years). On univariate analysis, higher mFI-5 score was significantly associated with increased risks of superficial surgical site infection, deep surgical site infection, wound dehiscence, unplanned reoperation, pneumonia, unplanned intubation, postoperative ventilator use, progressive renal insufficiency, acute renal failure, urinary tract infection, stroke, myocardial infarction, cardiac arrest, pulmonary embolism, deep vein thrombosis, bleeding requiring transfusion, sepsis, septic shock, and longer hospital length of stay (LOS). On multivariate logistic regression, increasing mFI-5 score versus a mFI-5 score of zero was associated with higher odds of overall complications (mFI-5 ≥2: odds ratio [OR] 1.38 CI: 1.24-1.54, P < 0.001; mFI-5 = 1: OR 1.18 CI: 1.11-1.24, P < 0.001) and 30-day mortality (mFI-5 ≥2: OR 2.33 CI: 1.60-3.38, P < 0.001). CONCLUSION: This study demonstrates that frailty, when measured using the mFI-5, independently predicts postoperative complications, hospital LOS, and 30-day mortality after surgical repair of thoracolumbar fractures. These findings are important for risk stratification in patients undergoing thoracolumbar fusion surgery and for standardization in reporting outcomes after those procedures.

Influence of Varying Oil-Water Contents on the Formation of Crude Oil Emulsion and Its Demulsification by a Lab-Grown Nonionic Demulsifier.

This study describes how varying oil/water contents affect emulsion formation and the impact they have on emulsion droplet size, viscosity, and interfacial behavior. Crude oil (continuous phase) volume fractions of 40, 50, 60, and 70 vol % were probed in the various W/O emulsions formed. Experimental results from optical morphology revealed the emulsion droplets kept reducing as the crude oil fraction kept increasing, while the droplets were nearly unnoticeable in the emulsions derived from 60 and 70% crude oil. The viscosity-shear rate of emulsions produced from 40, 50, and 60 vol % crude oil exhibited a non-Newtonian behavior owing to the substantial volume of water content in their emulsions, whereas the viscosity-shear rate of the emulsion with 70 vol % crude oil exhibited a Newtonian behavior similar to the pure crude oil, suggesting a thorough blending of oil-water at this crude oil fraction. Besides, the viscosity-temperature measurements revealed that the viscosity of these emulsions diminished as the temperature increased and the viscosity reduction became more noticeable in an emulsion comprising 70 vol % crude oil. In the interfacial assessment, the increased crude oil content in the produced emulsion led to a sharp reduction in the interfacial tension (IFT). The IFT values after 500 s contacts between the emulsion and water (surrounding phase) were 11.86, 10.02, 8.08, and 6.99 mN/m for 40, 50, 60, and 70 vol % crude oil, respectively. Demulsification experiments showed that water removal becomes more challenging with a large volume of crude oil and a small water content. Demulsification performances of the lab-grown nonionic demulsifier (NID) after 10 h of demulsification activity at room temperature (25 °C) were 98, 90, 17.5, and 10% for the emulsions formed from 40, 50, 60, and 70 vol % crude oil, respectively, indicating that the demulsification degree decreases with an increasing crude oil content. Viscosity-time determination was applied to affirm the activity of NID on the emulsion formulated with a 50% crude oil fraction. The injection of NID in this emulsion triggered a sharp viscosity reduction, indicating the adsorption of NID at the oil-water interface and disruption of emulsifiers, enabling emulsion stability.

Polymorphous adenocarcinoma of minor salivary gland: Case presentation and literature review.

INTRODUCTION AND IMPORTANCE: Polymorphous low-grade adenocarcinoma (PLGA) is a rare neoplasm arising from minor salivary glands, representing approximately 3 % of head and neck tumors. The clinical presentation of PLGA is defined as a painless, slow-growing tumor, mostly occurring in the palate. We report a case of PLGA with a rare presentation. CASE PRESENTATION: A 76-year-old male, known case of hepatitis B, diabetes, and hypertension, presented to the emergency department complaining of spitting blood and dysphagia. Imaging showed a heterogeneous enlarged left tonsil with hyperemia of the mucosa, and air foci. Biopsy with excisional biopsy confirmed the diagnosis of PLGA. The patient underwent completion tonsillectomy and selective neck dissection which yielded tonsillar tissue with underlying PLGA, and reactive lymph nodes with no malignant tissue respectively, margins were negative for malignancy. CLINICAL DISCUSSION: Polymorphous low-grade adenocarcinoma is a rare lesion with clinical behavior resembling that of a benign neoplasm. Predominantly occurring in the oral cavity, especially on the hard palate, buccal mucosa, and retromolar region, with fewer cases in the upper lip. Occurrence in the nasopharynx and oropharynx is rare. PLGA presents as painless slow-growing masses, typically in females aged 50-60. Local excision with careful margin evaluation is the preferred treatment, with good prognosis compared to other carcinomas. CONCLUSION: PLGA is rare, with limited reported case from around the world. It is mostly seen in adults between their fifth and sixth decades with female predominance. PLGA is diagnosed using imaging, immunohistochemistry. Owing to the limited cases there is no standard approach to treating PLGA. However, most cases are managed with local excision and showed an excellent response in terms of tumor nonrecurrence.

Electrophysiology and 3D-imaging reveal properties of human intracardiac neurons and increased excitability with atrial fibrillation.

Altered autonomic input to the heart plays a major role in atrial fibrillation (AF). Autonomic neurons termed ganglionated plexi (GP) are clustered on the heart surface to provide the last point of neural control of cardiac function. To date the properties of GP neurons in humans are unknown. Here we have addressed this knowledge gap in human GP neuron structure and physiology in patients with and without AF. Human right atrial GP neurons embedded in epicardial adipose tissue were excised during open heart surgery performed on both non-AF and AF patients and then characterised physiologically by whole cell patch clamp techniques. Structural analysis was also performed after fixation at both the single cell and at the entire GP levels via three-dimensional confocal imaging. Human GP neurons were found to exhibit unique properties and structural complexity with branched neurite outgrowth. Significant differences in excitability were revealed between AF and non-AF GP neurons as measured by lower current to induce action potential firing, a reduced occurrence of low action potential firing rates, decreased accommodation and increased synaptic density. Visualisation of entire GPs showed almost all neurons are cholinergic with a small proportion of noradrenergic and dual phenotype neurons. Phenotypic distribution differences occurred with AF including decreased cholinergic and dual phenotype neurons, and increased noradrenergic neurons. These data show both functional and structural differences occur between GP neurons from patients with and without AF, highlighting that cellular plasticity occurs in neural input to the heart that could alter autonomic influence on atrial function. KEY POINTS: The autonomic nervous system plays a critical role in regulating heart rhythm and the initiation of AF; however, the structural and functional properties of human autonomic neurons in the autonomic ganglionated plexi (GP) remain unknown. Here we perform the first whole cell patch clamp electrophysiological and large tissue confocal imaging analysis of these neurons from patients with and without AF. Our data show human GP neurons are functionally and structurally complex. Measurements of action potential kinetics show higher excitability in GP neurons from AF patients as measured by lower current to induce action potential firing, reduced low firing action potential rates, and decreased action potential accommodation. Confocal imaging shows increased synaptic density and noradrenergic phenotypes in patients with AF. Both functional and structural differences occur in GP neurons from patients with AF that could alter autonomic influence on atrial rhythm.

A Cross-Sectional Study of Anesthesia Safety in Wad Medani, Sudan: A Pre-war Status Indicating a Post-war Crisis.

BACKGROUND: As the surgical burden grows, increasing patient safety during anesthesia and surgery becomes a major global public health priority. Anesthesia can be safely administered in higher-income countries, yet it is more challenging in third-world countries. This study focuses on Sudan, a third-world country, and its unmet anesthetic needs before the current war and how these needs might compromise the post-war status. AIM: The aim of this study is to compare Sudan's outstanding anesthesia requirements to the World Health Organization's safe anesthesia practice standards in terms of workforce, medications, equipment, and anesthesia conduct. METHODS: This study was carried out in four hospitals (Wad Medani Teaching Hospital, Wad Medani Maternity Hospital, Gezira Centre for Renal and Urological Surgeries, and the National Centre for Pediatric Surgeries) in Wad Medani, two of which were referral and two were state-run. Each hospital from every category was identified using a convenience sampling technique. The World Health Organization-World Federation of Societies of Anesthesiologists International Standard and earlier regional African publications were used to determine the minimum predicted safe anesthesia needs. RESULTS: The results of our study demonstrate that overall, the hospitals surveyed fulfilled the minimum standards set by the World Health Organization and the World Federation of Societies of Anesthesiologists (WHO-WFSA) for safe anesthesia practice by 73% with no significant difference in the safety of anesthesia practice between state and referral hospitals. CONCLUSIONS: The state of safe anesthesia care in Wad Medani hospitals surveyed fell well short of the expected minimal criteria due to important requirements such as patient monitoring indicators, the inaccessibility of life-saving facilities such as defibrillators, and difficult intubation instruments. More importantly, the conduct of anesthesia was far below the standard.

First-in-human stage III/IV melanoma​ clinical trial of immune priming agent IFx-Hu2.0.

IFx-Hu2.0 was designed to encode part of the Emm55 protein contained within a plasmid in a formulation intended for transfection into mammalian cells. IFx-Hu2.0 promotes both adaptive and innate immune responses in animal studies. Furthermore, previous studies have demonstrated safety/efficacy in equine, canine, and murine species. We present the first-in-human study of IFx-Hu2.0, administered by intralesional injection into melanoma tumors of seven patients with stage III/IV unresectable melanoma. No dose-limiting toxicities attributable to IFx-Hu2.0 were observed. Grade 1/2 injection site reactions were observed in five of seven patients. IgG and IgM responses were seen in the peripheral blood to Emm55 peptides and known melanoma antigens, suggesting that IFx-Hu2.0 acts as an individualized "in-situ vaccine." Three of four patients previously refractory to anti-PD1 experienced clinical benefit upon subsequent anti-PD1-based treatment. Therefore, this approach is feasible, and clinical/correlative outcomes warrant further investigation for treating metastatic melanoma patients as an immune priming agent.

Repositioning of anti-infective compounds against monkeypox virus core cysteine proteinase: a molecular dynamics study.

Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, an in silico technique was applied to screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected after screening and processed for exhaustive docking based on the docked score of ≤ -9.5 kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔGTOTAL from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.

Jagged2 targeting in lung cancer activates anti-tumor immunity via Notch-induced functional reprogramming of tumor-associated macrophages.

Signaling through Notch receptors intrinsically regulates tumor cell development and growth. Here, we studied the role of the Notch ligand Jagged2 on immune evasion in non-small cell lung cancer (NSCLC). Higher expression of JAG2 in NSCLC negatively correlated with survival. In NSCLC pre-clinical models, deletion of Jag2, but not Jag1, in cancer cells attenuated tumor growth and activated protective anti-tumor T cell responses. Jag2-/- lung tumors exhibited higher frequencies of macrophages that expressed immunostimulatory mediators and triggered T cell-dependent anti-tumor immunity. Mechanistically, Jag2 ablation promoted Nr4a-mediated induction of Notch ligands DLL1/4 on cancer cells. DLL1/4-initiated Notch1/2 signaling in macrophages induced the expression of transcription factor IRF4 and macrophage immunostimulatory functionality. IRF4 expression was required for the anti-tumor effects of Jag2 deletion in lung tumors. Antibody targeting of Jagged2 inhibited tumor growth and activated IRF4-driven macrophage-mediated anti-tumor immunity. Thus, Jagged2 orchestrates immunosuppressive systems in NSCLC that can be overcome to incite macrophage-mediated anti-tumor immunity.

Gastrointestinal decontamination using oil-based solutions in patients with acute aluminum phosphide poisoning: a systematic review and meta-analysis.

Some studies suggested that gastrointestinal (GIT) decontamination with oil may improve the prognosis of patients who ingested aluminum phosphide (AlP). The aim of this study is to compare the efficacy and safety of gastric lavage with oil-based solutions to any method of gastric decontamination not using oils in patients presenting with acute AlP poisoning. The literature was searched for English-published randomized controlled trials (RCTs) from inception to 16 September 2023. The searched electronic databases included MEDLINE/PubMed, Cochrane Library, Web of Science, Egyptian Knowledge Bank, Scopus, and Google Scholar. Data were extracted and pooled by calculating the risk ratio (RR) for categorical outcomes and standardized mean difference (SMD) for numerical outcomes, with 95% confidence intervals (CI). Seven RCTs were included. Paraffin oil was significantly associated with a lower risk of mortality (RR = 0.59 [95% CI: 0.45, 0.76], p < .001), intubation (RR = 0.59 [95% CI: 0.46, 0.76], p < .001) and vasopressor need (RR = 0.71 [95% CI: 0.56, 0.91], p = .006). Survival time was significantly prolonged with paraffin oil (SMD = 0.72 [95% CI: 0.32, 1.13], p < .001). Coconut oil was significantly associated with prolonged survival time (SMD = 0.83 [95% CI: 0.06, 1.59], p = .03) as well as decreased risk of requiring intubation (RR = 0.78 [95% CI: 0.62, 0.99], p = .04). Oil-based GIT decontamination using paraffin oil showed benefits over conventional lavage regarding the incidence of in-hospital mortality and endotracheal intubation, and survival time. Coconut oil showed some benefits in terms of the intubation incidence and survival time. Decontamination using paraffin oil is recommended. Future clinical trials are warranted with larger sample sizes and focusing on cost-benefit and safety.

Whole-Exome Sequencing Identifies DYNC2H1 Mutations as a Cause of Jeune Asphyxiating Thoracic Dystrophy Without Extra-Skeletal Organ Involvement.

Jeune syndrome, or asphyxiating thoracic dystrophy (JATD), is a rare autosomal recessive skeletal dysplasia with heterogeneous genetic and clinical phenotypes, which primarily affects cartilage and bone development. Herein, we report a patient with a lethal form of SRTD3 without polydactyly (JATD), which led to severe restrictive lung disease and fatal respiratory failure. A full-term boy was born to a 30-year-old mother who was known to have hypothyroidism and was on thyroxine. The parents were first-degree cousins and had one healthy older son. Fetal ultrasound showed a cephalic fetus, normal amniotic fluid and a fundal placenta. All long bones and ribs were below the 1% percentile. The femur was bowed with no fractures or signs of significant demineralization at time of imaging. Head and abdominal circumference were within normal range. An echocardiogram on the 2nd day of life showed severe pulmonary hypertension (PHTN). Nitric oxide was started due to the presence of persistent hypoxia and severe PHTN. The patient continued to require high cardiorespiratory support, but the medical condition worsened, and respiratory failure persisted. The patient died of severe respiratory failure at 16 days of life due to respiratory insufficiency secondary to a severely restricted thoracic cage. Whole-exome sequencing (WES) revealed a homozygous mutation in the DYNC2H1 (NM_001377.3) gene, namely, the c.9041G>T NP_001368.2: p.(Arg3014Ile) missense variant, which results in the substitution of the arginine codon at amino acid position 3014 with an isoleucine codon. The phenotyping of the patient's JATD and the detection of a homozygous variant in the DYNC2H1 gene confirmed the diagnosis of short-rib thoracic dysplasia-3 without polydactyly. In summary, the patient had isolated skeletal anomalies without polydactyly or other organ involvement. Additionally, the infant had severe PHTN on top of the respiratory failure, which eventually caused death. Considerably more work will need to be done to determine the clinical spectrum of JATD and understand its genetic heterogeneity.

Preliminary study of a new online and equipment-free vision screening alternative for remote and isolated community.

INTRODUCTION: Vision screening has been initiated to detect potential vision problems, paving referral pathways towards a full eye examination. Time-cost-labour practicality challenges of equipment-based vision screening have lingered for decades. Going for the highest sensitivity and specificity or opting for a pragmatic and affordable vision screening program remains a dilemma in public eye health. We aimed to report the development of a new online and equipment-free vision screening called Eye: Questionnairebased Vision Screening (EyeQVS). We also analysed the visual profile of Orang Bateq resided in a remote locality, using findings from EyeQVS, single test vision screening and full eye examination. MATERIALS AND METHODS: Multi-perspective development strategies were employed in designing EyeQVS. The questionnaire items were constructed using the working backward technique, compiling common vision disorders from the literature and face validation using expert panels. Face validation and usability assessment were performed on EyeQVS. The vision screening was carried out using EyeQVS and single test visual acuity screening method. The full eye examination included visual acuity, refraction, binocular vision and ocular health assessment. The visual profile of indigenous people (Orang Bateq) at Kampung Bengoi and Kampung Atok, Jerantut, Pahang was analysed using EyeQVS, single test visual acuity screening method and full eye examination. RESULTS: The performance of EyeQVS was affirmative in both face validation and usability. About 95% of Orang Bateq failed full eye examination, while 55% failed EyeQVS screening. None of them failed single test vision screening. Binocular disorders and dry eye problems were commonly found in Orang Bateq. EyeQVS unearthed more various vision problems compared to the single test vision screening (visual acuity alone) as a screening tool in a remote location. CONCLUSION: EyeQVS can screen for binocular disorders and dry eyes problem commonly found among indigenous people, which might be missed using a single-test visual acuity screening approach. EyeQVS is a practical alternative for vision screening in places where financial or location hinders eye healthcare access.

Pancytopenia with aplastic anemia in systemic lupus erythematosus: case series and literature review.

Aplastic anemia (AA) is a rare, potentially catastrophic hematopoiesis failure manifested by pancytopenia and bone marrow aplasia. AA occurrence in Systemic Lupus Erythematosus (SLE) patients is extremely rare. The diagnosis may be delayed due to other possible pancytopenia etiologies. Confirmation of peripheral cytopenias diagnosis necessitates a bone marrow aspiration. The management of AA is challenging, and the literature reported using glucocorticoids, danazol, plasmapheresis, cyclophosphamide, intravenous immunoglobulin, and cyclosporine. We report two cases of SLE patients who presented with pancytopenia, with bone marrow biopsy confirmed AA. One case was treated with cyclophosphamide but unfortunately succumbed to Acute Respiratory Distress Syndrome (ARDS), while the other case was managed with rituximab with a good response. Interestingly, both patients were on azathioprine before the diagnosis of AA. A comprehensive search for reported cases of AA in PubMed, Scopus, and the Directory of Open Access Journals databases was performed to enhance the understanding of the diagnostic and management challenges associated with AA in SLE, facilitating ongoing exploration and research in this field. The decision to do a BM aspiration and biopsy is recommended for SLE patients with an abrupt decline in blood counts and previously stable blood counts.

Sex Differences and Clinical Outcomes of Patients with Coronavirus Disease 2019 Infection and Cerebral Venous Sinus Thrombosis: A Systematic Review.

Cerebral venous sinus thrombosis (CVST) is a rare neurovascular condition that has been observed in individuals with coronavirus disease 2019 (COVID-19). This systematic review aimed to explore the sex differences and characteristics of concurrent COVID-19 and CVST cases. A total of 212 CVST patients were included in the study. Women with CVST had a slightly higher mean age compared to men (47.359 years vs 46.08 years). Women were more likely to report symptoms such as fever (56.1%) and decreased sense of smell or taste (71.4%), while men more frequently experienced nausea or vomiting (55.6%), headache (62.9%), and seizures (72%). Notably, current smokers, who were predominantly men, had a higher occurrence of CVST. On the other hand, women had a higher likelihood of CVST risk factors such as oral contraceptive pill (OCP) use and autoimmune diseases. Treatment approaches also showed sex-based differences. Unfractionated heparin was administered more often to women with CVST (63.2%). The in-hospital mortality rate for CVST patients was 21.3%, with men having a significantly higher mortality rate than women (65.2% vs 34.8%, P = .027). Survival analysis revealed that factors such as smoking history, diabetes mellitus, hypertension, OCP use, COVID-19 symptoms, CVST symptoms, and the need for intubation significantly influenced survival outcomes. Understanding these sex differences in COVID-19-related CVST is crucial for accurate diagnosis and effective management, ultimately leading to improved patient outcomes. Our findings highlight the importance of considering sex as a factor in the evaluation and treatment of individuals with COVID-19 and concurrent CVST.

Treatment of Stage III Resectable Melanoma-Adjuvant and Neoadjuvant Approaches.

ABSTRACT: Patients with stage III resectable melanoma carry a high risk of melanoma recurrence that ranges from approximately 40% to 90% at 5 years following surgical management alone. Postoperative systemic adjuvant therapy targets residual micrometastatic disease that could be the source of future recurrence and death from melanoma. Randomized phase III adjuvant trials reported significant improvements in overall survival with high-dose interferon α in 2 of 3 studies (compared with observation and GMK ganglioside vaccine) and with anti-cytotoxic T-lymphocyte antigen 4 ipilimumab at 10 mg/kg compared with placebo and ipilimumab 3 mg/kg compared with high-dose interferon α. In the modern era, more recent phase III trials demonstrated significant recurrence-free survival improvements with anti-programmed cell death protein 1, pembrolizumab, and BRAF-MEK inhibitor combination dabrafenib-trametinib (for BRAF mutant melanoma) versus placebo. Furthermore, anti-programmed cell death protein 1, nivolumab and pembrolizumab have both been shown to significantly improve recurrence-free survival as compared with ipilimumab 10 mg/kg. For melanoma patients with clinically or radiologically detectable locoregionally advanced disease, emerging data support an important role for preoperative systemic neoadjuvant therapy. Importantly, a recent cooperative group trial (S1801) reported superior event-free survival rates with neoadjuvant versus adjuvant therapy. Collectively, current data from neoadjuvant immunotherapy and targeted therapy trials support a future change in clinical practice in favor of neoadjuvant therapy for eligible melanoma patients.

Astigmatism Management in Modern Cataract Surgery.

Astigmatism management is a frequently encountered challenge in the world of modern cataract surgery. This review article investigates the importance of astigmatic correction and seeks to uncover the critical components of preoperative evaluation. With the rapid growth of new technologies and techniques, this article aims to also catalogue and clarify the multitude of astigmatism treatment options available for the cataract surgeon.