A roadmap to human hippocampal neurogenesis in adulthood, aging and AD.

In the rodent, hippocampal neurogenesis plays critical roles in learning and memory1,2, is tightly regulated by inhibitory neurons3-7 and contributes to memory dysfunction in Alzheimer's disease (AD) mouse models8-10. In contrast, the mechanisms regulating neurogenesis in the adult human hippocampus, the dynamic shifts in the transcriptomic and epigenomic profiles in aging and AD and putative niche interactions within the cellular environment, remain largely unknown. Using single nuclei multi-omics of postmortem human hippocampi we map the molecular mechanisms of hippocampal neurogenesis across aging, cognitive decline, and AD neuropathology. Transcriptomic and epigenetic profiling of neural stem cells (NSCs), neuroblasts and immature neurons suggests that the earliest shift in the characteristics of neurogenesis takes place in NSCs in aging. Cognitive impairment was associated with changes in neuroblast profile. In AD, there was a widespread cessation of the transcription machinery in immature neurons, with robust downregulation of genes regulating ribosomal and mitochondrial function. Further, there was substantial loss of parvalbumin+ inhibitory neurons in the hippocampus in aging. The number of the rest of inhibitory neurons were reduced as a function of age and diagnosis. Notably, a similar system-level effect was observed between immature and inhibitory neurons in the transition from aging to AD, manifested by common molecular pathways that were ultimately lost in AD. The numbers of neuroblasts, immature and GABAergic neurons inversely correlated with extent of neuropathology. Using CellChat and NeuronChat, we inferred the ligands and receptors by which neurogenic cells communicate with their cellular environment. Loss of synaptic adhesion molecules and neurotransmitters, either sent or received by neurogenic cells, was observed in AD. Together, this study delineates the molecular mechanisms and dynamics of human neurogenesis, functional association with inhibitory neurons and a mechanism of hippocampal hyperexcitability in AD.

Gastrointestinal stromal tumor of the duodenum presenting with shock and massive upper and lower gastrointestinal bleeding: a case report and review of the literature.

BACKGROUND: Due to rarity of duodenal GISTs, clinicians have few information about its clinical features, diagnosis, management and prognosis. CASE REPORT: We report a case of promptly diagnosed duodenal GIST in a 61-year-old Egyptian man presented shocked with severe attack of hematemesis and melena. Upper gastroduodenal endoscopy was done and revealed a large ulcerating bleeding mass at first part of duodenum 4 hemo-clips were applied with good hemostasis. An exploratory laparotomy and distal gastrectomy, duodenectomy and gastrojejunostomy were performed. The morphology of the mass combined with immunohistochemistry was consistent with duodenal gastrointestinal stromal tumours (GISTs) of high risk type. The patient is on amatinib one tablet daily and he was well with no evidence of tumor recurrence. CONCLUSION: despite being rare, emergency presentation with sudden severe, life-threatening hemorrhagic shock duodenal GISTs might be a cause of potentially lethal massive combined upper and lower gastrointestinal bleeding which is the key feature of this rare and challenging tumor.

Isolated dentinogenesis imperfecta: Novel DSPP variants and insights on genetic counselling.

OBJECTIVE: Dentinogenesis imperfecta (DI) is an inherited dentin defect and may be isolated or associated with disorders such as osteogenesis imperfecta, odontochondrodysplasia Ehler-Danlos and others. Isolated DI is caused mainly by pathogenic variants in DSPP gene and around 50 different variants have been described in this gene. Herein, we report on 19 patients from two unrelated Egyptian families with isolated DI. Additionally, we focused on genetic counselling of the two families. MATERIALS AND METHODS: The patients were examined clinically and dentally. Panoramic X-rays were done to some patients. Whole exome sequencing (WES) and Sanger sequencing were used. RESULTS: WES revealed two new nonsense variants in DSPP gene, c.288T > A (p.Tyr96Ter) and c.255G > A (p.Trp85Ter). Segregation analysis by Sanger sequencing confirmed the presence of the first variant in all affected members of Family 1 while the second variant was confirmed to be de novo in the patient of Family 2. CONCLUSIONS AND CLINICAL RELEVANCE: Our study extends the number of DSPP pathogenic variants and strengthens the fact that DSPP is the most common DI causative gene irrespective of patients' ethnicity. In addition, we provide insights on genetic counseling issues in patients with inherited DSPP variants taking into consideration the variable religion, culture and laws in our society.

Brachyolmia, dental anomalies and short stature (DASS): Phenotype and genotype analyses of Egyptian and Pakistani patients.

Brachyolmia is a heterogeneous group of developmental disorders characterized by a short trunk, short stature, scoliosis, and generalized platyspondyly without significant deformities in the long bones. DASS (Dental Abnormalities and Short Stature), caused by alterations in the LTBP3 gene, was previously considered as a subtype of brachyolmia. The present study investigated three unrelated consanguineous families (A, B, C) with Brachyolmia and DASS from Egypt and Pakistan. In our Egyptian patients, we also observed hearing impairment. Exome sequencing was performed to determine the genetic causes of the diverse clinical conditions in the patients. Exome sequencing identified a novel homozygous splice acceptor site variant (LTBP3:c.3629-1G > T; p. ?) responsible for DASS phenotypes and a known homozygous missense variant (CABP2: c.590T > C; p.Ile197Thr) causing hearing impairment in the Egyptian patients. In addition, two previously reported homozygous frameshift variants (LTBP3:c.132delG; p.Pro45Argfs*25) and (LTBP3:c.2216delG; p.Gly739Alafs*7) were identified in Pakistani patients. This study emphasizes the vital role of LTBP3 in the axial skeleton and tooth morphogenesis and expands the mutational spectrum of LTBP3. We are reporting LTBP3 variants in seven patients of three families, majorly causing brachyolmia with dental and cardiac anomalies. Skeletal assessment documented short webbed neck, broad chest, evidences of mild long bones involvement, short distal phalanges, pes planus and osteopenic bone texture as additional associated findings expanding the clinical phenotype of DASS. The current study reveals that the hearing impairment phenotype in Egyptian patients of family A has a separate transmission mechanism independent of LTBP3.

Cardiac Arrest Following Retrieval of Inferior Vena Cava Filter: A Case Report and Literature Review of Pericardial Effusion and Cardiac Tamponade.

This report presents the clinical details and management of a 58-year-old Caucasian male with pericardial effusion and cardiac tamponade following outpatient inferior vena cava (IVC) filter removal. The patient was unresponsive and experienced cardiac arrest minutes after the procedure, requiring cardiopulmonary resuscitation. After return of spontaneous circulation he displayed somnolence, confusion and chest discomfort. Investigations revealed a large pericardial effusion, and an echocardiography confirmed cardiac tamponade. Prompt intervention involved pericardiocentesis, resulting in haemodynamic stabilisation and reduction in effusion size. The patient responded favourably with treatment. Differential diagnoses were considered and treatment options were discussed, highlighting the importance of timely recognition and appropriate intervention in managing pericardial effusion and cardiac tamponade. This report adds to the limited literature on pericardial effusion and cardiac tamponade following a scheduled outpatient IVC filter removal, emphasising the unique clinical presentation and successful management of this rare phenomenon. LEARNING POINTS: Understanding the link between pericardial effusion and cardiac tamponade following IVC filter removal.Recognising and differentiating cardiac tamponade from other emergencies using clinical and diagnostic tools.Learning the immediate management of cardiac tamponade, emphasising the role of pericardiocentesis.

Short duration of dual antiplatelet therapy following complex percutaneous coronary intervention: A systematic review and meta-analysis.

INTRODUCTION AND AIM: The optimal composition and duration of antiplatelet therapy after complex percutaneous coronary intervention (PCI) remains unclear. We conducted a meta-analysis to compare 1-3 months of dual antiplatelet therapy (DAPT) followed by monotherapy vs. 12 months of DAPT. METHOD: MEDLINE/PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were queried for studies comparing 1-3 months of DAPT followed by monotherapy vs. 12 months of DAPT in the outcomes of complex PCI from inception through January 2023. Outcomes of interest included major bleeding, all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stent thrombosis, target vessel revascularization, and stroke. RESULTS: Compared to 12 months, 1-3 months of dual antiplatelet therapy had a weak association with less major bleeding (OR 0.67; 95 % CI, 0.44-1.00; p = 0.05; I2 = 28 %). There were no significant differences between the shorter and longer antiplatelet therapy in terms of all-cause mortality (OR 0.83; 95 % CI, 0.59-1.16; p = 0.21; I2 = 17 %), cardiovascular mortality (OR 0.87; 95 % CI, 0.53-0.42; p = 0.50; I2 = 0), MI (OR 0.97; 95 % CI, 0.69-1.35; p = 0.82; I2 = 32 %), stent thrombosis (OR 1.17, 95 % CI, 0.77-1.76; p = 0.38; I2 = 0 %), target vessel revascularization (OR 1.05, 95 % CI, 0.58-1.89; p = 0.82; I2 = 64 %), or stroke (OR 1.10, 95 % CI, 0.55-2.17; p = 0.37; I2 = 7 %);. CONCLUSION: Among patients undergoing complex PCI, DAPT for 1-3 months may be associated with less major bleeding but similar rates of cardiovascular events (death, MI, stroke, stent thrombosis, and revascularization) compared to DAPT for 12 months.

Sex Differences in the Clinical Outcomes of Patients With Takotsubo Stress Cardiomyopathy: A Meta-Analysis of Observational Studies.

The incidence of takotsubo stress cardiomyopathy (TSCM) in males is low compared with females. Gender-based differences in clinical outcomes of TSCM are not well characterized. The aim of this meta-analysis was to analyze whether gender-based differences are observed in TSCM clinical outcomes. A comprehensive literature search of PubMed, Embase, Cochrane Library database, and Web of Science was performed from inception to June 20, 2022, for studies comparing the clinical outcomes between male and female patients with TSCM. The primary outcome of interest was in-hospital all-cause mortality and cardiogenic shock. The secondary outcomes were cardiovascular mortality, receipt of mechanical ventilation, intra-aortic balloon pump, occurrence of ventricular arrhythmia, and left ventricular thrombus. A random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). Heterogenicity was assessed using the Higgins I2 index. Twelve observational studies involving 51,213 patients (4,869 males and 46,344 females) were included in the meta-analysis. Male gender was associated with statistically significant higher in-hospital all-cause mortality compared with females in patients with TSCM (RR 2.17, 95% CI 1.77 to 2.67, p <0.001). The rate of cardiogenic shock was significantly higher in males with TSCM compared with females (RR 1.66, 95% CI 1.29 to 2.12, p <0.001). Our meta-analysis showed a difference in the clinical outcomes of TSCM between men and women. Male gender was associated with a two-fold greater in-hospital all-cause mortality risk compared with female gender. The higher mortality risk associated with male gender deserves further study, particularly whether it represents later recognition of the condition and disparities in treatments.

Bivalirudin versus unfractionated heparin in patients with myocardial infarction undergoing percutaneous coronary intervention: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Bivalirudin is an alternative accepted therapy to unfractionated heparin for patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). We aimed in this meta-analysis to compare bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. METHODS: We have screened PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov (inception through January 8th, 2023) for randomized controlled trials (RCTs) evaluating bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. The DerSimonian and Laird method was used for estimation of tau2 to calculate the risk ratio (RR) and 95 % confidence interval (CI). RESULTS: Ten RCTs with a total of 40,069 participants were included in our analysis. Bivalirudin as compared with unfractionated heparin was associated with significant decrease in major bleeding (RR 0.64 [0.52 to 0.79]; p < 0.01; I2 = 69 %) and cardiovascular mortality (RR 0.79 [0.67 to 0.92]; p < 0.01; I2 = 0 %). There was no significant difference between bivalirudin and unfractionated heparin groups in terms of major adverse cardiovascular events (RR 1.02 [0.91 to 1.14]; p = 0.73; I2 = 52 %), all-cause mortality (RR 0.89 [0.77 to 1.04]; p = 0.15; I2 = 23 %), MI (RR 1.02 [0.87 to 1.19]; p = 0.80; I2 = 36 %), stent thrombosis (RR 1.12 [0.52 to 2.40]; p = 0.77; I2 = 82 %), or stroke (RR 0.97 [0.73 to 1.29]; p = 0.85; I2 = 0 %). CONCLUSION: Our meta-analysis suggests that bivalirudin compared with unfractionated heparin in patients with MI undergoing PCI was associated with lower rates of major bleeding and cardiovascular mortality without a significant difference in major adverse cardiovascular events, all-cause mortality, MI, stroke, or stent thrombosis.

Safety and Efficacy of Cangrelor in Acute Coronary Syndromes: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Cangrelor is a potent intravenous non-thienopyridine P2Y12 inhibitor. We conducted a network meta-analysis to study the efficacy and safety of cangrelor as compared with the oral P2Y12 inhibition, clopidogrel, or placebo in acute coronary syndromes. METHODS: This meta-analysis followed the Cochrane collaboration guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. Outcomes of interest included all-cause mortality, myocardial infarction, stent thrombosis, target vessel revascularization, major bleeding, minor bleeding, and the need for blood transfusion. RESULTS: The analysis was comprised of 6 studies including 26,444 patients treated with cangrelor, clopidogrel, or placebo. There were no statistically significant differences in the incidence of all-cause mortality, myocardial infarction, stent thrombosis, target vessel revascularization, or major bleeding. Cangrelor was associated with a higher risk of minor bleeding than clopidogrel or placebo, with no difference in requiring blood transfusion. CONCLUSION: Cangrelor has comparable outcomes to clopidogrel in patients with acute coronary syndromes and can be used as a reliable alternative in this population.

Papillon-Lefevre syndrome in twelve Egyptian patients: Five novel CTSC variants and functional characterization of a missense variant and its effect on splicing.

OBJECTIVES: describing the clinical features of twelve Egyptian patients with Papillon-Lefever syndrome (PLS). Five novel mutations in the cathepsin C (CTSC) gene are introduced and the phenotype of the syndrome is expanded by the identification of new clinical features. DESIGN: the clinical, oro-dental data of twelve Egyptian patients from seven unrelated families are described. Sequence analysis of the CTSC gene was performed to identify the causative mutaions. RESULTS: Typical PLS features were presented in all patints but with variable severity. One patient showed atypical dental features including dental structural defect, minimal periodontitis, severe gingivitis, and delayed closure of root apices. Another patient presented with arachnodactyly, dystrophic nails, and buphthalmos in the right eye secondary to uncontrolled congenital glaucoma. Mutational analysis of CTSC gene revealed seven distinct homozygous variants including five novel ones: c.285_286delGT (p.Leu96GlufsTer2), c .302 G>C (p.Trp101Ser), c.622_628delCACAGTC (p.H208Efs*11), c.1331delinsAAAAA (p.G444Efs*4) and c .1343 G>A (p.Cys448Tyr). The previously reported missense variant c .757 G>A (p.Ala253Thr) was found in one patient. This variant is very close to the splice region and by functional studies, we proved that it results in exon skipping and early protein truncation (p.R214Sfs*46). CONCLUSION: We report five novel CTSC variants and describe rare and unusual associated clinical and dental findings such as dental structural defects, delayed closure of root apices, and congenital glaucoma. Therefore, our results expand both the phenotypic and mutational spectrum of PLS.

Successful Management of Severe Bupropion Toxicity with Lipid Emulsion Therapy: A Complex Case Report and Literature Review.

This case report presents the management of a 53-year-old female with a complex psychiatric history who ingested multiple medications, resulting in severe cardiovascular compromise and subsequent respiratory failure. The patient's ingestion included clonidine, fluoxetine, gabapentin, quetiapine and bupropion. Initial treatment involved supportive measures, including fluid resuscitation, bicarbonate infusion and correction of electrolyte imbalances. Despite these interventions, the patient remained haemodynamically unstable, requiring multiple vasopressors. Lipid emulsion therapy was initiated and led to a remarkable improvement in the patient's cardiovascular status. However, she developed acute respiratory distress syndrome (ARDS) and required prolonged mechanical ventilation. Steroid therapy was initiated to manage the ARDS, and the patient was successfully extubated on day 6. The case highlights the potential effectiveness of lipid emulsion therapy in managing bupropion toxicity, but emphasises the need for further research to establish clear guidelines on dosing, timing and safety protocols. Adverse effects associated with lipid emulsion therapy must be carefully considered. Individualised decision-making and patient-centred care is crucial in optimising outcomes in cases of bupropion toxicity. LEARNING POINTS: Recognise the cardiotoxic effects of bupropion toxicity: be vigilant in identifying cardiotoxic effects such as prolonged QTc, hypotension and arrhythmias in cases of bupropion toxicity.Consideration of intravenous lipid emulsion therapy for toxic injections of lipophilic drugs such as bupropion: in severe lipophilic drug ingestions, such as bupropion, consider using intravenous lipid emulsion therapy as a potential treatment option.Individualised decision-making and monitoring is necessary when using lipid emulsion therapy: tailor treatment based on the patient's condition and closely monitor for responses and potential adverse effects when using lipid emulsion therapy.

Biosynthesis and characterization of silver nanoparticles from Punica granatum (pomegranate) peel waste and its application to inhibit foodborne pathogens.

Polyphenolics have been predicted to effectively develop antimicrobial agents for the food industry as food additives and promote human health. This study aims to synthesize pomegranate peel extract (PPE) with silver nanoparticles (AgNPs) against eight foodborne pathogens. Multispectroscopic analysis of UV-vis spectroscopy, Zeta potential, Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) analysis were used to characterize the interaction between PPE and AgNPs. Eight foodborne pathogenic strains (six bacterial and two fungal strains) Bacillus subtilis ATCC 6633, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 8379, Klebsiella pneumoniae ATCC 00607, Salmonella typhi DSM 17058, Shigella sonnei DSM 5570, Aspergillus flavus ATCC 9643, and Rhizopus oryzae ATCC 96382 were used to test the inhibitory potential of PPW-AgNPs. The reaction colour of PPE-AgNPs from yellow to brown indicated that the nanoparticles were successfully formed. The UV absorption of PPE-AgNPs was detected at 440 nm of 0.9 SPR. SEM image of PPE-AgNPs exhibited spherical shapes with a zeta potential of - 20.1 mV. PPE-AgNPs showed high antimicrobial activity against all tested strains. The highest inhibition activity of PPE-AgNPs was recorded for the B. subtilis strain followed by K. pneumonia, while the highest resistance was noticed for R. oryzae. The components of pomegranate peel were analyzed using gas chromatography-mass spectrometry (GC-MS). The major constituents of pomegranate peel is phenol (51.1%), followed by Isocitronellol (19.41%) and 1-Propanol, 2-(2-hydroxypropyl)- (16.05%). PPE is key in the simple, eco-friendly green synthesis of extracellular stable AgNPs as an alternative source for harmful chemical disinfectants.

Spinal dural arteriovenous fistula masquerading as a herniated disc: illustrative case.

BACKGROUND: Spinal dural arteriovenous fistula (SDAVF) is a rare disorder with an unknown etiology. Often, the clinical presentation and imaging findings are misleading, causing this condition to be mistaken for other entities, such as demyelinating or degenerative spinal lesions. OBSERVATIONS: The authors report a challenging case of SDAVF in which the patient's symptoms were initially thought to be attributable to a herniated disc based on his imaging studies at another institution. He sought the authors for a second opinion, which yielded a confirmed diagnosis of SDAVF. Due to his rapidly progressive neurological manifestations, he underwent a surgical division of the fistula using intraoperative video angiography via indocyanine green injections. His symptoms progressively improved over a 3-month period. He regained full sphincter control by 4 months, which gave him a better recovery than seen in other patients with SDAVFs, who do not generally fully regain sphincter control. LESSONS: SDAVF is a critical spinal vascular pathology that should not be overlooked in the differential diagnosis of any patient presenting with signs of progressive myelopathy. Despite its associated vague initial clinical symptoms, SDAVF typically, but not always, demonstrates a characteristic imaging appearance on magnetic resonance (MR) imaging studies; therefore, MR angiography is still required for definitive diagnosis. Surgical treatment for SDAVF is almost always definitive and curative.

Efficacy and safety of the new generation Watchman FLX device compared to the Watchman 2.5: a systematic review and meta-analysis.

INTRODUCTION: The first-generation Watchman 2.5 (W 2.5)TM presented several limitations, such as challenges in implantation within complex left atrial appendage (LAA) anatomies, higher incidence of peri-device leak, device recapture, and device-related thrombus (DRT). The newer generation Watchman FLX (W-FLX)TM was introduced with a modified design aiming to overcome these limitations. The purpose of this meta-analysis is to conduct a comparative assessment of the safety and efficacy of the W-FLX and 2.5 devices in clinical practice. METHOD: The meta-analysis was conducted according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA). Studies were located through a search strategy utilizing PubMed, Cochrane, Google scholar and MEDLINE from inception to March 2023, with a primary objective to compare the safety and efficacy of the W-FLX and W 2.5 devices. After applying the selection criteria, five studies were included in this analysis. RESULTS: The analysis included five studies comprising 54,727 patients. The W-FLX is associated with an increase in procedural success (OR 7.49 [95% CI 1.98-28.26, P = 0.02; I2 = 0%]), and a significant reduction in mortality (OR 0.52 [95% CI 0.51-0.54, P<0.01; I2 = 0%], major bleeding 0.57 [95% CI 0.51-0.64, P<0.01; I2 = 0%]), device embolism (OR 0.35 [95% CI 0.18-0.70, P = 0.02; I2 = 0%]), and pericardial effusion (OR 0.33 [95% CI 0.26-0.41, P<0.01; I2 = 0%]). The rates of DRT and stroke were similar between the two groups. CONCLUSION: Compared to the W 2.5, the W-FLX was associated with a higher procedural success rate and significantly reduced adverse outcomes including mortality, major bleeding, device embolization, and pericardial effusion.

Syncope as the Sole Presentation of Multi-Vessel Coronary Artery Disease.

Defining the etiology of syncope can be occasionally challenging. We present a case with no history of coronary artery disease (CAD) who presented exclusively with exertional syncope, and was found to have mildly reduced left ventricular systolic dysfunction on echocardiogram and severe multi-vessel CAD with chronic total occlusion (CTO) of the right coronary artery (RCA). Syncope as the initial presentation of advanced CAD in the absence of classic ischemic symptoms is rather an uncommon presentation in clinical practice.

A case report of severe hyponatremia secondary to Paxlovid-induced SIADH.

Nirmatrelvir-ritonavir (Paxlovid) is a brand-new oral antiviral medication for treating mild to severe COVID-19. The Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for ritonavir-nirmatrelvir on December 22, 2021, to treat COVID-19. We describe a case of mild COVID-19 infection who developed severe hyponatremia following the administration of Paxlovid. Clinical and laboratory evaluations suggest SIADH, likely secondary to Paxlovid. The potential side effects of this medication still require further study.

Microbial colonization of sacral nerve stimulators pseudo-capsule: A single institution experience.

PURPOSE: To evaluate the incidence and type of microbial colonization of the pseudo-capsule (PC) that forms around sacral nerve stimulators (SNS) and consequently the significance of surgical excision of this PC at time of SNS revision or removal. MATERIALS AND METHODS: A cohort of 31 patients who underwent SNS revision or removal from January 2018 to June 2021 were retrospectively reviewed. The baseline demographics, rate and type of PC microbial colonization and development of SNS insertion site infection were reported. RESULTS: A cohort of 31 patients who underwent "InterStim device (Medtronic)" revision or removal were included. The majority were females (93.5%). The most common indication for SNS insertion was refractory overactive bladder (67.7%). Nine patients (29.0%) underwent SNS revision due to malfunctional device, and 9 patients had SNS removal for the need of MRI procedures. Four patients (12.9%) had positive tissue culture growing Coryneform bacillus (50.0%), Cutibacterium acnes (25.0%) and Pseudomonas aeruginosa (25.0%). CONCLUSIONS: PC colonization was uncommon at the time of SNS explant. However, more research is needed to better understand the role of PC-positive culture in increasing the risk of SNS device infections if strict adherence to sterile techniques is adopted.

The impact of interaction between verteporfin and yes-associated protein 1/transcriptional coactivator with PDZ-binding motif-TEA domain pathway on the progression of isocitrate dehydrogenase wild-type glioblastoma.

Verteporfin and 5-ALA are used for visualizing malignant tissue components in different body tumors and as photodynamic therapy in treating isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM). Additionally, verteporfin interferes with Yes-associated protein 1 (YAP)/Transcriptional coactivator with PDZ-binding motif - TEA domain (TAZ-TEAD) pathway, thus inhibiting the downstream effect of these oncogenes and reducing the malignant properties of GBM. Animal studies have shown verteporfin to be successful in increasing survival rates, which have led to the conduction of phase 1 and 2 clinical trials to further investigate its efficacy in treating GBM. In this article, we aimed to review the novel mechanism of verteporfin's action, the impact of its interaction with YAP/TAZ-TEAD, its effect on glioblastoma stem cells, and its role in inducing ferroptosis.

Meta-Analysis of the Outcomes of Peri-Device Leak After Left Atrial Appendage Closure.

Left atrial appendage closure (LAAC) reduces the risk of thromboembolic stroke in atrial fibrillation. Peri-device leak (PDL) after LAAC may affect the subsequent risk of thromboembolism. We conducted a systematic review and meta-analysis to evaluate the effect of PDL after LAAC. We searched PubMed/Medline, Embase, and Google Scholar for studies reporting outcomes of PDL after LAAC from inception through October 2022. The primary outcome was the composite of stroke, transient ischemic attack (TIA), or systemic embolism (SE). Secondary outcomes included all-cause and cardiovascular mortality, ischemic stroke, TIA, and device-related thrombus. Outcomes were pooled using random-effects models. We used I2 statistics to assess statistical heterogeneity; I2 >50% considered significant heterogeneity. This study included 54,279 patients from 11 studies (6 observational, 2 nonrandomized controlled trials [non-RCTs] primary results, 2 RCT post hoc analyses, and 1 analysis combining 2 RCTs data). PDL was associated with a significant increase in the composite outcome of stroke, TIA, or SE (odds ratio 1.63, 95% confidence interval 1.06 to 2.52, p = 0.03, I2 = 43%) as compared with cases with no PDL. There were no significant differences in all-cause or cardiovascular mortality, ischemic stroke, TIA, or device-related thrombus. In conclusion, PDL after LAAC is associated with an increased risk of thromboembolism (composite stroke, TIA, or SE) without impacting mortality.