Quantifying Placenta Accreta Spectrum Severity and its associated Blood Loss: A Novel Transvaginal Ultrasound Scoring System.

BACKGROUND: Hemorrhage associated with placenta accreta spectrum (PAS) is a leading cause of maternal morbidity and mortality. Estimating blood loss in these individuals is a critical component of comprehensive preoperative planning. OBJECTIVE: A semi-quantitative score based on transvaginal ultrasound was developed and tested to predict PAS, estimate its severity, and blood loss in individuals with clinical and ultrasound evidence suggesting PAS. STUDY DESIGN: A secondary analysis was conducted of prospectively collected data from a quaternary center of patients with suspected accreta on 2D ultrasound and clinical suspicion. A pre-determined scoring system was applied based on three components: 1) uterine wall (score 0: no loss of hypo-translucent uterine wall with overlying placenta in the lower uterine segment; 1: loss of hypo-translucent <3-cm defect; 2: 3-6-cm defect; and 3: >6-cm defect); 2) arterial vascularity at the uterine wall defect (score 0: no vessels observed; 1: 1-2 vessels over the defect; 2: 3-5 vessels; and 3: >5 vessels) and 3) cervical involvement (score 0: normal cervical length without previa; 1: previa with normal cervical length; 2: short cervix with previa, minimal vascularity and small lacunae; 3: short cervix with previa, increased vascularity and large lacunae). Each patient's three domain scores determined a cumulative, final score of 0-9. Patients were managed at the discretion of a multi-disciplinary team and patient's preference among the following options: cesarean delivery with placenta removal, cesarean delivery with placenta in-situ (conservative) with or without delayed hysterectomy, or cesarean hysterectomy. The frequency of different degrees of placental invasion per pathology examination per score unit was registered. Multiple linear regression analysis was performed for association of blood loss according to score adjusted by risk factors for PAS. RESULTS: A total of 73 patients were evaluated. All 11 patients who had a score of 0 had cesarean delivery with placenta removal without evidence of intraoperative PAS, thus resulting in a 100% negative predictive value. The remaining 62 had scores between 1-9. Among patients with scores 0-3 (n=20), only one had intraoperative PAS, yielding a negative predictive value of 97%. Higher scores were associated with severe PAS forms (r=0.301, p=0.02). Based on the associations between PAS scores, clinical correlation, and blood loss, we divided patients into four categories: Category 0: PAS score 0; Category 1: scores 1-3; Category 2: scores 4-6; and Category 3: scores 7-9. The median blood loss in Category 0 = 635 ± 352 mL, Category 1 = 634 ± 599 mL, Category 2 = 1549 ± 1284 mL, and Category 3 = 1895 ± 2106 mL (p <0.001). On multivariable analysis, Category 2 (ß = 0.97, p <0.01) and Category 3 (ß = 1.26, p <0.003) were associated with significantly greater blood loss than Category 0, irrespective of type of surgery. CONCLUSION: The transvaginal ultrasound score separates groups at low risk (Category 0) and at higher risk of PAS (Categories 1-3). Categories 1-3 may provide important clinical information to estimate the risk of severe forms of PAS and of blood loss during surgery.

Ocular TB in Western Australia.

This was a retrospective chart review in Western Australia, Australia.To describe the diagnosis, management, and treatment outcomes of ocular TB in Western Australia (WA).This was a retrospective review of ocular TB cases in WA from 2007 to 2018 with a minimum 2-year follow-up upon completion of anti-TB therapy (ATT).A total of 44 patients were referred to WA TB clinic. Ten were excluded from the analysis of treatment response; 34 met the inclusion criteria, of whom 97.1% were born overseas. No patients had symptomatic extraocular TB. Chest X-ray showed prior pulmonary TB in 11.7% of patients (n = 4). All patients were treated with three or four ATT drugs. The most common ocular TB manifestation was retinal vasculitis (23.5%). Full resolution of ocular inflammation following ATT occurred in 66.7% (n = 22), and reduced ocular inflammation requiring only topical steroid treatment was seen in 21.2% (n = 7). Treatment failure occurred in 12.1% (n = 4). Side effects were reported in 45.6% of patients, with gastrointestinal symptoms most common (27.2%).Our study is the first Australian study examining the management of ocular TB. Our study highlights the challenges in diagnosing TB ocular disease in a low-endemicity setting and the importance of the collaboration between uveitis and TB subspecialists..

Pro-Oxidant Auranofin and Glutathione-Depleting Combination Unveils Synergistic Lethality in Glioblastoma Cells with Aberrant Epidermal Growth Factor Receptor Expression.

Glioblastoma (GBM) is the most prevalent and advanced malignant primary brain tumor in adults. GBM frequently harbors epidermal growth factor receptor (EGFR) wild-type (EGFRwt) gene amplification and/or EGFRvIII activating mutation. EGFR-driven GBM relies on the thioredoxin (Trx) and/or glutathione (GSH) antioxidant systems to withstand the excessive production of reactive oxygen species (ROS). The impact of EGFRwt or EGFRvIII overexpression on the response to a Trx/GSH co-targeting strategy is unknown. In this study, we investigated Trx/GSH co-targeting in the context of EGFR overexpression in GBM. Auranofin is a thioredoxin reductase (TrxR) inhibitor, FDA-approved for rheumatoid arthritis. L-buthionine-sulfoximine (L-BSO) inhibits GSH synthesis by targeting the glutamate-cysteine ligase catalytic (GCLC) enzyme subunit. We analyzed the mechanisms of cytotoxicity of auranofin and the interaction between auranofin and L-BSO in U87MG, U87/EGFRwt, and U87/EGFRvIII GBM isogenic GBM cell lines. ROS-dependent effects were assessed using the antioxidant N-acetylsteine. We show that auranofin decreased TrxR1 activity and increased ROS. Auranofin decreased cell vitality and colony formation and increased protein polyubiquitination through ROS-dependent mechanisms, suggesting the role of ROS in auranofin-induced cytotoxicity in the three cell lines. ROS-dependent PARP-1 cleavage was associated with EGFRvIII downregulation in U87/EGFRvIII cells. Remarkably, the auranofin and L-BSO combination induced the significant depletion of intracellular GSH and synergistic cytotoxicity regardless of EGFR overexpression. Nevertheless, molecular mechanisms associated with cytotoxicity were modulated to a different extent among the three cell lines. U87/EGFRvIII exhibited the most prominent ROS increase, P-AKT(Ser-473), and AKT decrease along with drastic EGFRvIII downregulation. U87/EGFRwt and U87/EGFRvIII displayed lower basal intracellular GSH levels and synergistic ROS-dependent DNA damage compared to U87MG cells. Our study provides evidence for ROS-dependent synergistic cytotoxicity of auranofin and L-BSO combination in GBM in vitro. Unraveling the sensitivity of EGFR-overexpressing cells to auranofin alone, and synergistic auranofin and L-BSO combination, supports the rationale to repurpose this promising pro-oxidant treatment strategy in GBM.

Aspirin 162 mg versus 81 mg for Preeclampsia Prophylaxis in High-risk Obese Individuals: A Comparative Effectiveness Open Label Randomized Trial (ASPREO).

BACKGROUND: In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia (PE) in women at risk, whereas the NICE guidelines in the UK recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommend doses. OBJECTIVE: We evaluated whether daily administration of 162 mg aspirin would be more effective compared to 81 mg in decreasing the rate of PE with severe features in high-risk obese pregnant individuals. STUDY DESIGN: We performed a randomized trial between May 2019 and November 2022. Individuals at 12 to 20-weeks gestational age (GA) with a BMI ≥ 30 kg/m2 at time to enrollment, and at least one of three high risk factors: history of PE in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pre-gestational diabetes or gestational diabetes diagnosed prior to 20 weeks GA were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were: multifetal gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin due to other indications, or contraindication to aspirin. The primary outcome was PE with severe features (PE or superimposed PE with severe features, eclampsia, or HELLP). Secondary outcomes included rates of preterm birth due to PE, small for gestational age (SGA), postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior. RESULTS: Of 343 eligible individuals, 220 (64.1%) were randomized. The primary outcome was available for 209/220 (95%). Baseline characteristics were similar between groups, median gestational age at enrollment was 15.9 weeks in the 162 mg aspirin group and 15.6 weeks in the 81 mg aspirin group. Enrollment prior to 16 weeks occurred in 55/110 of those assigned to 162 mg and 58/110 of those assigned to 81 mg of aspirin. The primary outcome occurred in 35% in the 162 mg aspirin group and in 40% in the 81 mg aspirin group (posterior relative risk, 0.88; 95% credible interval, 0.64-1.22). Bayesian analysis indicated a 78% probability of a reduction in the primary outcome with 162 mg aspirin compared to 81 mg aspirin dose. Rates of indicated preterm birth due to preeclampsia (21% vs 21%), SGA (6.5% vs 2.9%), abruption (2.8% vs 3.0%) and postpartum hemorrhage (10% vs 8.8%) were similar between groups. Medication adverse effects were also similar. CONCLUSION: Among high-risk obese individuals, there was 78% probability of benefit that 162 mg aspirin compared to 81 mg will decrease the rate of PE with severe features. With a best estimate of a 12% reduction when using 162 mg of aspirin in comparison to 81 mg of aspirin in this population. This trial supports doing a larger multicenter trial.

Well-Child Visits for Early Detection and Management of Maternal Postpartum Hypertensive Disorders.

Importance: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders. Objective: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management. Design, Setting, and Participants: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022. Exposures: BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed. Main Outcome and Measures: Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables. Results: A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia. Conclusions and Relevance: This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.

A Case Report of Bilateral Optic Perineuritis With Idiopathic Intracranial Hypertension: Challenges in Diagnosis and Management.

Optic perineuritis (OPN) refers to the inflammation of the optic nerve sheath and it is a rare form of idiopathic orbital inflammatory disease. We report a rare case of bilateral OPN in an obese female teenager with idiopathic intracranial hypertension (IIH). She was initially presented with painless bilateral blurring of vision that was progressively worsening for three weeks duration. Visual acuity of both eyes was hand movement with no relative afferent pupillary defect detected. The confrontation visual field test showed central scotoma. Both anterior segments were unremarkable. Fundoscopy showed a swollen optic disc bilaterally, with extensive flame-shaped hemorrhages surrounding the disc area and dot blot hemorrhages in the posterior pole. A magnetic resonance imaging scan of the brain and orbit revealed the presence of bilateral optic nerve sheath enhancement with empty sella turcica. The patient was diagnosed with bilateral OPN with IIH. She received an initial high dose of systemic corticosteroid followed by a slow tapering dose. She was monitored by the neuromedical team for her IIH. She was followed up for about a year. The final best corrected visual acuity in the right eye was 6/36 and the left eye was 6/60. In conclusion, OPN poses challenges in diagnosis and management. This case emphasizes the importance of considering OPN in the differential diagnosis of optic nerve-related symptoms, as prompt recognition and intervention are crucial for favorable outcomes.

Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells.

High-grade serous ovarian cancer (HGSOC) accounts for 70% of ovarian cancer cases, and the survival rate remains remarkably low due to the lack of effective long-term consolidation therapies. Clinical remission can be temporarily induced by platinum-based chemotherapy, but death subsequently results from the extensive growth of a platinum-resistant component of the tumor. This work explores a novel treatment against HGSOC using the gold complex auranofin (AF). AF primarily functions as a pro-oxidant by inhibiting thioredoxin reductase (TrxR), an antioxidant enzyme overexpressed in ovarian cancer. We investigated the effect of AF on TrxR activity and the various mechanisms of cytotoxicity using HGSOC cells that are clinically sensitive or resistant to platinum. In addition, we studied the interaction between AF and another pro-oxidant, L-buthionine sulfoximine (L-BSO), an anti-glutathione (GSH) compound. We demonstrated that AF potently inhibited TrxR activity and reduced the vitality and viability of HGSOC cells regardless of their sensitivities to platinum. We showed that AF induces the accumulation of reactive oxygen species (ROS), triggers the depolarization of the mitochondrial membrane, and kills HGSOC cells by inducing apoptosis. Notably, AF-induced cell death was abrogated by the ROS-scavenger N-acetyl cysteine (NAC). In addition, the lethality of AF was associated with the activation of caspases-3/7 and the generation of DNA damage, effects that were also prevented by the presence of NAC. Finally, when AF and L-BSO were combined, we observed synergistic lethality against HGSOC cells, which was mediated by a further increase in ROS and a decrease in the levels of the antioxidant GSH. In summary, our results support the concept that AF can be used alone or in combination with L-BSO to kill HGSOC cells regardless of their sensitivity to platinum, suggesting that the depletion of antioxidants is an efficient strategy to mitigate the course of this disease.

COVID-19 vaccine safety and side effects in children aged 5-11 years: a cross-sectional study.

INTRODUCTION: The COVID-19 pandemic has prompted a global drive for vaccination, including children. Despite the urgency, understanding the safety and side effects remains crucial. Our study aimed to evaluate the safety of the Pfizer- BioNTech (BNT162b2) vaccine in children by determining the proportion of vaccinated children who experienced side effects and identifying factors associated with postvaccination side effects. MATERIALS AND METHODS: A cross-sectional study was conducted among children who received the COVID-19 vaccine between 3 February and 8 May 2022. Data were collected using a self-administered questionnaire filled out by the parent or legal guardian. RESULTS: The mean age of the study participants was 9 years old and 43.1% were males. Out of the 195 participants in the study, 62 (31.8%) reported side effects after vaccination. The most frequently reported side effects were pain at the injection site (29.7%, n=58), fever (15.9%, n=31), localised inflammation (10.8%, n=21) and arthralgia/myalgia (9.2%, n=18). There were no reported severe adverse events such as anaphylaxis or myocarditis. Most side effects occurred within the first two days post-vaccination. There was a higher proportion of side effects among children with underlying co-morbidities. No significant differences were observed based on age, weight, ethnicity and the presence of allergies, or the use of premedication. CONCLUSION: The BNT162b2 vaccine was generally welltolerated in children, with most side effects being mild and self-limiting. These findings support the safety of the COVID-19 vaccine and would guide healthcare professionals, parents and policy-makers in making informed decisions about COVID-19 vaccination, especially among high-risk groups.

Endovascular Treatment plus Medical Treatment versus Medical Treatment Alone in Ischemic Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION: This study was conducted to assess the hypothesis that endovascular treatment in addition to medical treatment improve stroke mortality and post-stroke disability. METHODS: In this systematic review and meta-analysis, the studies were included if they were randomized controlled trials in design and compared between endovascular treatment and medical therapy versus medical therapy alone in stroke management. RESULTS: The search yielded 22 articles that included 5,049 patients. The analysis showed significant association between the intervention and reduction in disability measured by Modified Rankin Scale (mRS) (mRS = 0-2) (odds ratio [OR] = 1.61; 95% confidence intervals [95% CI]: 1.27-2.06) and National Institute of Health Stroke Scale (NIHSS) (NIHSS = 0-15) (OR = 2.13; 95% CI: 1.04-4.34). Also, we found a significant difference in disability scores between the intervention and the medical therapy group (mRS weighted mean difference [WMD] = -0.59; 95% CI: -1.15 to -0.02, NIHSS WMD = -4.52; 95% CI: -6.32 to -2.72). Additionally, there was significant reduction in mortality in the intervention group (OR = 0.79; 95% CI: 0.68-0.92). There was no significant difference in the rate of any serious adverse effects between the two study groups except for asymptomatic intracerebral hemorrhage. CONCLUSION: Our study provides strong evidence stemmed from randomized clinical trials that endovascular treatment combined with medical therapy is superior to medical therapy alone in the management of stroke.

Microglial cytokines poison neuronal autophagy via CCR5, a druggable target.

In the prodromal phase of neurodegenerative diseases, microglia switch to an activated state resulting in increased secretion of pro-inflammatory factors. We reported that C - C chemokine ligand 3 (CCL3), C - C chemokine ligand 4 (CCL4) and C - C chemokine ligand 5 (CCL5) contained in the secretome of activated microglia inhibit neuronal autophagy via a non-cell autonomous mechanism. These chemokines bind and activate neuronal C - C chemokine receptor type 5 (CCR5), which, in turn, promotes phosphoinositide 3-kinase (PI3K) - protein kinase B (PKB, or AKT) - mammalian target of rapamycin complex 1 (mTORC1) pathway activation, which inhibits autophagy, thus causing the accumulation of aggregate-prone proteins in the cytoplasm of neurons. The levels of CCR5 and its chemokine ligands are increased in the brains of pre-manifesting Huntington disease (HD) and tauopathy mouse models. CCR5 accumulation might be due to a self-amplifying mechanism, since CCR5 is a substrate of autophagy and CCL5-CCR5-mediated autophagy inhibition impairs CCR5 degradation. Furthermore, pharmacological, or genetic inhibition of CCR5 rescues mTORC1-autophagy dysfunction and improves neurodegeneration in HD and tauopathy mouse models, suggesting that CCR5 hyperactivation is a pathogenic signal driving the progression of these diseases.

Pericardial fat and cardiovascular diseases: A systematic review and meta-analysis.

OBJECTIVE: Previous studies investigated the effect of pericardial fat on cardiovascular diseases. However, until now there was no systematic review and meta-analysis investigated this association, thus we conducted this article to assess the relationship between pericardial fat and cardiovascular diseases. METHODS: We searched PubMed, The Cochrane Library, Scopus, Google Scholar and Clinicaltrials.gov to select observational studies reported the relationship between pericardial fat and cardiovascular diseases including coronary artery disease (CAD), ventricular dysfunction, heart failure (HF), atrial fibrillation (AF), major adverse cardiac events (MACE), coronary artery calcifications (CAC), arrhythmias other than atrial fibrillation, and cardiovascular events prediction scores. Meta XL 5.3 was used for data analysis. RESULTS: A total of 83 articles that included 73,934 patients were included in our analysis. The results showed that pericardial fat was significantly associated with CAD (OR = 1.38; 95% CI: 1.28-1.50), ventricular dysfunction (OR = 1.53 per 1 mm3 ; 95% CI: 1.17-2.01), HF (OR = 1.32 per 1 mm3 ; 95% CI: 1.23-1.41), AF (OR = 1.16 per 1 mm3 ; 95% CI: 1.09-1.24), MACE (OR = 1.39 per 1 mm3 ; 95% CI: 1.22-1.57), and CAC (OR = 1.15 per 1 mm3 ; 95% CI: 1.05-1.27). On the other hand, there was no enough data about the relationship between pericardial fat with arrhythmias other than atrial fibrillation or cardiovascular risk scores. CONCLUSION: The analysis demonstrated that the relationship between pericardial fat volume and cardiovascular diseases was significant. Since pericardial fat is a good predictor of obesity, it suggests investigating its relationship and adds on effect to previously established risk factor to evaluate the possibility of incorporating it with cardiovascular risk scores.

The delaying of elective surgeries after COVID-19 infection decreases postoperative complications.

BACKGROUND: Huge controversy surrounds delaying elective surgeries after COVID-19 infection. Although two studies evaluated the issue, several gaps still exist. METHODS: A propensity score matched retrospective single center cohort design was used to evaluate the optimum time of delaying elective surgeries after COVID-19 infection and the validity of the current ASA guidelines in this regard. The exposure of interest was a previous COVID-19 infection. The primary composite included the incidence of death, unplanned Intensive Care Unit admission or postoperative mechanical ventilation. The secondary composite included the occurrence of pneumonia, acute respiratory distress, or venous thromboembolic. RESULTS: The total number of patients was 774, half of them had a history of COVID-19 infection. The analysis revealed that delaying surgeries for 4 weeks was associated with significant reduction in primary composite (AOR = 0.02; 95%CI: 0.00-0.33) and the length of hospital stay (B = 3.05; 95%CI: 0.41-5.70). Furthermore, before implementing the ASA guidelines in our hospital, a significant higher risk for the primary composite (AOR = 15.15; 95%CI: 1.84-124.44; P-value = 0.011) was observed compared to after applying it. CONCLUSION: Our study showed that the optimum period of delaying elective surgery after COVID-19 infection is four weeks, with no further benefits from waiting for longer times. This finding provide further support to the current ASA guidelines about delaying elective surgeries. Further large-scale prospective studies are needed to give more evidence-based support to the appropriateness of the 4-week waiting time for elective surgeries after COVID-19 infection and to investigate the effect of type of surgery on the required delay.

Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration.

In neurodegenerative diseases, microglia switch to an activated state, which results in excessive secretion of pro-inflammatory factors. Our work aims to investigate how this paracrine signaling affects neuronal function. Here, we show that activated microglia mediate non-cell-autonomous inhibition of neuronal autophagy, a degradative pathway critical for the removal of toxic, aggregate-prone proteins accumulating in neurodegenerative diseases. We found that the microglial-derived CCL-3/-4/-5 bind and activate neuronal CCR5, which in turn promotes mTORC1 activation and disrupts autophagy and aggregate-prone protein clearance. CCR5 and its cognate chemokines are upregulated in the brains of pre-manifesting mouse models for Huntington's disease (HD) and tauopathy, suggesting a pathological role of this microglia-neuronal axis in the early phases of these diseases. CCR5 upregulation is self-sustaining, as CCL5-CCR5 autophagy inhibition impairs CCR5 degradation itself. Finally, pharmacological or genetic inhibition of CCR5 rescues mTORC1 hyperactivation and autophagy dysfunction, which ameliorates HD and tau pathologies in mouse models.

Significance of Statin-Associated Muscle Symptoms and Its Impact on Patients Adherence and Outcomes.

ABSTRACT: Statin-associated muscle symptoms (SAMS) are one of the most common side effects of statins. This study aimed to explore the significance of SAMS among statin users by comparing statin users with a control group. To achieve our aims, a propensity score matching the retrospective cohort study was conducted in a single center tertiary hospital. The statin muscle symptoms were assessed using the Proposed Statin Myalgia Index Score, whereas the patient's adherence to medications was evaluated using the Morisky Medication Adherence Scale-8. We included 743 patients in our study; of them, 64.9% were on statin, whereas the rest were controls (35.1%). After propensity score matching, patients on statin had significantly higher rates of SAMS (5.0%) compared with control (1.6%) (AOR = 3.209; 95% CI: 1.020-10.091). However, there was no significant difference between statin users and controls in medications nonadherence ( P -value = 0.820). Our analysis among statins users revealed that moderate-intensity (2.671; 95% CI: 1.691-3.310) and high-intensity (3.552; 95% CI: 2.190-4.129) statin therapy was significantly associated with SAMS. In addition, autoimmune diseases were significantly associated with SAMS occurrence (AOR = 32.301; 95% CI: 1.785-584.374). Also, patients on PPIs had significantly less occurrence of SAMS (AOR = 0.145; 95% CI: 0.044-0.483), whereas patients on antiepileptic drugs had significantly higher SAMS occurrence (AOR = 72.337; 95% CI: 2.649-1975.201). Regarding MACE among statin users, there was no significant difference in the 1-year or 5-year MACE rate between statin users and controls. Our study suggests that SAMS are significant among statin users and must be addressed by health care providers to ensure that patients are still adherent to their medications and hence protected against cardiac events.

Perinatal risk factors for infantile hypertrophic pyloric stenosis: A systematic review and meta-analysis.

BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) is one of the most common diseases that require surgical intervention amongst the paediatric population. Although the treatment and the diagnosis of pyloric stenosis are well established, the perinatal risk factors associated with it still need further investigation. METHODS: We searched the following databases: Cochrane, Google Scholar, PubMed, and Scopus. Studies were included if they were case-control or cohort in design and studied the perinatal risk factors associated with IHPS. The quality of the included studies was assessed using the Newcastle-Ottawa scale (NOS). RESULTS: Twenty-one articles were included in this meta-analysis, including 18,104,753 participants. Our analysis showed a significant association between IHPS and male sex (RR=2.71, 95% CI:1.93-3.78), maternal smoking (RR=1.75, 95% CI: 1.54 - 2.00), bottle-feeding (RR=1.68, 95% CI: 1.42 - 1.98), being first born (RR=1.23, 95% CI:1.07-1.40), African ethnicity (RR=0.51, 95% CI: 0.35-0.75), and cesarean section (RR=1.57, 95% CI: 1.49-1.66). On the contrary, there was no significant association between IHPS and multiple gestations, preterm labour, being born in summer, and small for gestational age (SGA). CONCLUSION: In conclusion, our analysis showed that male sex, bottle feeding, maternal smoking and African ethnicity were significantly associated with the risk of IHPS. However, most of the included articles were retrospective in design which necessitates conducting future prospective well-designed studies to further investigate the risk factors of IHPS.

Infiltrative Optic Neuropathy in Advanced Breast Carcinoma.

Infiltrative optic neuropathy is a condition characterized by the invasion of tumor cells into the optic nerve. Breast carcinoma can metastasize to various organs, most commonly the bones, lungs, and liver, and rarely involves the orbit. Orbital involvement may result in debilitating visual impairment and blindness. We report a case of infiltrative optic neuropathy secondary to advanced breast carcinoma. A 39-year-old woman with stage 4 breast carcinoma presented with sudden-onset blurred vision in her right eye for one week. It was associated with a localized scotoma in the visual field. She was previously diagnosed with secondary metastases involving the liver and bone and is currently undergoing treatment with chemotherapy and radiotherapy. Visual acuity in the right eye was 6/7.5, with a positive relative afferent pupillary defect and an inferonasal field defect. The extraocular muscle movement was full, with no significant proptosis. Both anterior segments were unremarkable. Fundoscopy showed a normal optic disc in both eyes, with no optic disc swelling. A computed tomography (CT) scan of the brain and orbit revealed secondary metastases in the dura and right orbital apex. Magnetic resonance imaging (MRI) of the brain revealed right infiltrative optic neuropathy. The patient received whole-brain radiotherapy (WBRT), followed by 12 cycles of chemotherapy. On follow-up, the patient was stable; however, her vision in the right eye deteriorated from 6/7.5 to perception of light. In conclusion, orbital metastasis should be the leading diagnostic consideration when the affected patient has a history of cancer. Early detection, coupled with prompt treatment, can help patients achieve better visual outcomes and, whenever possible, preserve their vision.

Synergistic effects of silybin and curcumin on virulence and carbapenemase genes expression in multidrug resistant Klebsiella oxytoca.

OBJECTIVE: Silybin and curcumin have potential antimicrobial effects. This study aimed to evaluate the synergistic antimicrobial effects of silybin and curcumin on virulence and carbapenemase genes expression among multidrug-resistant (MDR) Klebsiella oxytoca. RESULTS: A total of 70 MDR K. oxytoca (carrying blaIMP and blaOXA-48-like genes) were included. The antibiotic susceptibility and biofilm production of isolates were determined. The silybin and curcumin at concentrations 10-500 mg/mL alone and in combination were exposed to bacterial isolates in Mueller Hinton broth medium for 24 h. The expression of blaIMP, blaOXA-48-like, mrkA, pilQ, matB and fimA genes was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). The mean minimum inhibitory concentration (MIC) of curcumin and silybin were 250 mg/mL and 500 mg/mL, respectively. The anti-virulent effect of 100 mg/mL of silybin and curcumin was shown by significant reduction in the expression of fimA (2.1-fold, P < 0.0001) and mrkA (2.1 fold, P < 0.0001) genes. Moreover, these compounds significantly decreased the expression of blaIMP1 (3.2-fold, P < 0.0001) gene. Notably, there was no significant effect on pilQ, matB and blaOXA-48-like genes. The results showed that silybin and curcumin can be candidate as natural way for control the MDR virulent strains of K. oxytoca.

Apoptotic susceptibility of pancreatic alpha cells to environmentally relevant dose levels of bisphenol-A versus dibutyl phthalate is mediated by HSP60/caspase-3 expression in male albino rats.

Unfortunately, humanity is exposed to mixed plasticizers such as bisphenol-A (BPA) and dibutyl phthalate (DBP) that are leached from the daily used plastic products. Previous studies have demonstrated their potential in pancreatic beta cell injury and diabetes induction. The study hypothesized that both compounds would affect the pancreatic alpha cells in albino rats when administered at environmentally relevant doses. Heat shock protein 60 (HSP60) and caspase-3 protein expression was also investigated as potential mechanisms. Thirty-six male Wistar albino rats were separated into four equal groups: control, BPA alone, DBP alone, and BPA + DBP combined groups. BPA and DBP were given in drinking water for 45 days in a dose of 4.5 and 0.8 µg/L, respectively. Fasting blood glucose, serum insulin, pancreatic tissue levels of malondialdehyde, and superoxide dismutase were measured. Pancreatic sections were subjected to hematoxylin & eosin (H & E) staining, glucagon, HSP60, and caspase-3 immunohistochemistry. Although all three experimental groups showed diffuse islet cell HSP60 immunoreactivity, rats exposed to BPA alone showed α-cell-only apoptosis, indicated by H & E changes and caspase-3 immunoreactivity, associated with reduced glucagon immunoreaction. However, rats exposed to DBP alone showed no changes in either α or ß-cells. Both combined-exposed animals displayed α and ß apoptotic changes associated with islet atrophy and reduced glucagon expression. In conclusion, the study suggested HSP60/caspase-3 interaction, caspase-3 activation, and initiation of apoptosis in α-cell only for BPA-alone exposure group, meanwhile DBP alone did not progress to apoptosis. Interestingly, both α/ß cell effect was observed in the mixed group implying synergetic/additive action of both chemicals when combined.

Safety and Efficacy of SSRIs in Improving Poststroke Recovery: A Systematic Review and Meta-Analysis.

Background Several studies investigated the role of selective serotonin reuptake inhibitors (SSRIs) in improving poststroke recovery; thus, we have decided to conduct this systematic review and meta-analysis to investigate the efficacy and safety of SSRIs in poststroke recovery. Methods and Results In this meta-analysis we searched the following databases: PubMed, Cochrane, Scopus, and Google Scholar. The studies were included if they were placebo-controlled trials in design and reported SSRIs' effects on poststroke depression, anxiety, disability, dependence, motor abilities, and cognitive functions. The quality of the included studies was assessed using the revised Cochrane risk-of-bias tool for randomized trials. The search yielded 44 articles that included 16 164 patients, and about half of the participants were treated with SSRIs. Our results showed that SSRIs had a significant effect on preventing depression (weighted mean difference [WMD], -7.05 [95% CI, -11.78 to -2.31]), treating depression according to the Hamilton Rating Scale for Depression score (WMD, -1.45 [95% CI, -2.77 to -0.14]), anxiety (relative risk, 0.23 [95% CI, 0.09-0.61]), dependence (WMD, 8.86 [95% CI, 1.23-16.48]), motor abilities according to National Institutes of Health Stroke Scale score (WMD, -0.79 [95% CI, -1.42 to -0.15]), and cognitive functions (WMD, 1.00 [95% CI, 0.12-1.89]). On the other hand, no significant effect of SSRIs on disability was observed. Additionally, we found that treating with SSRIs increased the risk of seizures (relative risk, 1.44 [95% CI, 1.13-1.83]), whereas there was no difference in the incidence of gastrointestinal symptoms or bleeding between SSRIs and a placebo. Conclusions Our study showed that SSRIs are effective in preventing and treating depression, and improving anxiety, motor function, cognitive function, and dependence in patients after stroke. These benefits were only reproducible with the citalopram subanalysis but not fluoxetine. Further well-conducted placebo-controlled trials are needed to investigate the safety and efficacy of citalopram among patients after stroke. Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021285766.

Performance, Barriers, and Satisfaction of Healthcare Workers Toward Electronic Medical Records in Saudi Arabia: A National Multicenter Study.

Background Electronic medical record (EMR) systems are nowadays available internationally, including in Saudi Arabia. Nevertheless, there are still many obstacles to overcome before their effective implementation. This cross-national study aimed to investigate the perceptions and practices of healthcare workers toward implemented EMR systems. Methods A cross-sectional study was conducted across selected hospitals in the four cities of Al-Ahsa, Dammam, Medina, and Riyadh in Saudi Arabia. Healthcare workers of all specialties were invited to participate in the study during the six-month study period from August 2019 to February 2020. The questionnaire was submitted online through institutional e-mails. Results The study included a total of 2684 healthcare providers. Almost half of the respondents (47.1%) were aged between 35 and 50 years. High experience with computer use was observed among 38.3% of them, while 54.3% attended EMR training activities. The performance scores of EMR's compared to previous routines had a median of 24 (interquartile range {IQR} = 0-38). The satisfaction scores with EMR's ranged between 16 and 80 with a median of 53 (IQR = 48-61). Older participants (>50 years), non-Saudis, and those who attended EMR training had statistically significant higher scores of both EMR performance and EMR satisfaction, (p<0.001). Those working in other medical specialties (not major) had statistically significant higher scores of EMR performance alone (p<0.001), while general practitioners (p<0.001) and females (p = 0.001) had statistically significant higher scores of EMR satisfaction alone. EMR systems' positive impact on quality of care was the highest agreed-upon benefit reported, while the temporary loss of access to patient records if computers crashed or power failed was the highest agreed-upon barrier. Conclusions The attitude and satisfaction of healthcare workers in Saudi Arabia towards EMR systems are acceptable particularly among those who are older, non-Saudi, and have attended EMR training. Improved quality of care was the main noted benefit of EMR's, followed by improved productivity. The temporary loss of access to patient records if computers crashed or power failed, followed by privacy and security concerns, was the major EMR barrier mentioned.