Citations

Background: The microRNAs (miRNAs) are small noncoding single-stranded RNAs typically 19–25 nucleotides long and regulated by cellular and epigenetic factors. These miRNAs plays important part in several pathways necessary for cancer development, an altered miRNA expression can be oncogenic or tumor-suppressive. Recent experimental results on miRNA have illuminated a different perspective of the molecular pathogenesis of head and neck cancers. Regulation of miRNA can have a detrimental effect on the efficacy of chemotherapeutic drugs in both neoadjuvant and adjuvant settings. This miRNA-induced chemoresistance can influence the prognosis and survival rate. The focus of the study is on how regulations of various miRNA levels contribute to chemoresistance in head and neck cancer (HNC). Recent findings suggest that up or down-regulation of miRNAs may lead to resistance towards various chemotherapeutic drugs, which may influence the prognosis. Methods: Studies on miRNA-specific chemoresistance in HNC were collected through literary (bibliographic) databases, including SCOPUS, PubMed, Nature, Elsevier, etc., and were systematically reviewed following PRISMA-P guidelines (Preferred Reporting Items for Systematic Review and Meta-analysis Protocol). We evaluated various miRNAs, their up and downregulation, the effect of altered regulation on the patient’s prognosis, resistant cell lines, etc. The data evaluated will be represented in the form of a review and meta-analysis. Discussion: This meta-analysis aims to explore the miRNA-induced chemoresistance in HNC and thus to aid further researches on this topic. PROSPERO registration: CRD42018104657.

Background High-impact pathogenic variants in more than a thousand genes are involved in Mendelian forms of neurodevelopmental disorders (NDD). Methods This study describes the molecular and clinical characterisation of 28 probands with NDD harbouring heterozygous AGO1 coding variants, occurring de novo for all those whose transmission could have been verified (26/28). Results A total of 15 unique variants leading to amino acid changes or deletions were identified: 12 missense variants, two in-frame deletions of one codon, and one canonical splice variant leading to a deletion of two amino acid residues. Recurrently identified variants were present in several unrelated individuals: p.(Phe180del), p.(Leu190Pro), p.(Leu190Arg), p.(Gly199Ser), p.(Val254Ile) and p.(Glu376del). AGO1 encodes the Argonaute 1 protein, which functions in gene-silencing pathways mediated by small non-coding RNAs. Three-dimensional protein structure predictions suggest that these variants might alter the flexibility of the AGO1 linker domains, which likely would impair its function in mRNA processing. Affected individuals present with intellectual disability of varying severity, as well as speech and motor delay, autistic behaviour and additional behavioural manifestations. Conclusion Our study establishes that de novo coding variants in AGO1 are involved in a novel monogenic form of NDD, highly similar to the recently reported AGO2 -related NDD.

Abstract Clinical significance of a single positive blood culture bottle (SPBCB) with Staphylococcus aureus is unclear. We aimed to assess the significance of an SPBCB by looking at the associated outcomes. We performed a retrospective, multicenter study of patients with an SPBCB with S aureus using data collected from both electronic health records and the clinical microbiology laboratory. Overall, 534 patients with S aureus bacteremia were identified and 118 (22.1%) had an SPBCB. Among cases with an SPBCB, 106 (89.8%) were classified as clinically significant whereas 12 (10.2%) were considered contaminated or of unclear significance. A majority (92.4%) of patients received antibiotic therapy, but patients with clinically significant bacteremia were treated with longer courses (25.9 vs 5.7 days, P < .001). Significant differences in both frequency of echocardiography (65.1% vs 84.6%, P < .001) and infective endocarditis diagnosis (3.8% vs 14.2%, P = .002) were seen in those with an SPBCB compared to those with multiple positive bottles. A longer hospital length of stay and higher 90-day, 6-month, and 1-year mortality rates were seen in patients with multiple positive blood culture bottles. An SPBCB with S aureus was common among our patients. While this syndrome has a more favorable prognosis as compared to those with multiple positive blood cultures, clinicians should remain concerned as it portends a risk of infective endocarditis and mortality.

Abstract Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

The Society for the Advancement of Transplant Anesthesia (SATA) is dedicated to improving patient care in all facets of transplant anesthesia. The anesthesia fellowship training recommendations for thoracic transplantation (heart and lungs) and part of the abdominal organ transplantation (liver) have been presented in previous publications. The SATA Fellowship Committee has completed the remaining component of abdominal transplant anesthesia (kidney/pancreas) and has assembled core competencies and milestones derived from expert consensus to guide the education and overall preparation of trainees providing care for kidney/pancreas transplant recipients. These recommendations provide a comprehensive approach to pre-operative evaluation, vascular access procedures, advanced hemodynamic monitoring, assessment of coagulation and metabolic abnormalities, operative techniques, and post-operative pain control. As such, this document supplements the current liver/hepatic transplant anesthesia fellowship training programs to include all aspects of “Abdominal Organ Transplant Anesthesia” recommended knowledge.

Abstract Background Severe acute respiratory syndrome coronavirus 2 vaccination is recommended for all individuals with inflammatory bowel disease (IBD), including those on immunosuppressive therapies; however, little is known about vaccine safety and efficacy in these patients or the impact of vaccination on IBD disease course. Methods We evaluated coronavirus disease 2019 (COVID-19) vaccine–related adverse events (AEs) and the effect of vaccination on IBD disease course among participants in the PREVENT-COVID (Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID) study, a prospective, observational cohort study. Localized and systemic reactions were assessed via questionnaire. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes. Results A total of 3316 individuals with IBD received at least 1 COVID-19 vaccine. Injection site tenderness (68%) and fatigue (46% dose 1, 68% dose 2) were the most commonly reported localized and systemic AEs after vaccination. Severe localized and systemic vaccine-related AEs were rare. The mRNA-1273 vaccine was associated with significantly greater severe AEs at dose 2 (localized 4% vs 2%, systemic 15% vs 10%; P < .001 for both). Prior COVID-19 infection, female sex, and vaccine type were associated with severe systemic reactions to dose 1, while age <50 years, female sex, vaccine type, and antitumor necrosis factor and vedolizumab use were associated with severe systemic reactions to dose 2. Overall rates (2%) of IBD flare were low following vaccination. Conclusions Our findings provide reassurance that the severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with IBD, which may help to combat vaccine hesitancy and increase vaccine confidence.

Abstract Background We describe and compare the clinical, diagnostic evaluation and outcomes of patients who underwent therapeutic management for pyogenic brain abscess. Methods We retrospectively reviewed adults who presented with pyogenic brain abscess from January 1, 2009 through June 30, 2020. Results 231 patients were identified during the study period. Sixty-one (26.4%) patients received antibiotic therapy alone, and 170 (73.6%) had a combination of antibiotic therapy and surgical intervention. The median age for the medical and combined therapy group was 59 years and 58 years, respectively. Patients who received medical treatment had a higher prevalence of infective endocarditis than those who received combined therapy (6.6% vs. 0.6%; P=0.005). The medical therapy group was more likely to have brain MRI and cranial CT than the patients with combined therapy (75.4% vs. 63.5%; P=0.041). Midline shift (11.5% vs. 31.2%; P=0.002), a single (21% vs. 83%; P=0.001) and greater size (1.4 cm vs. 2.5 cm; P=0.007) brain abscess was significant when comparing medical vs. surgically managed abscess. Stereotactic surgical technique was the preferred diagnostic approach for the medical group (65.6% vs. 46.5%; P=0.010), and excision/craniotomy for the combined group (31.1% vs. 53.5%; P=0.002). Streptococcus viridans group was the predominant organism (32.8% and 25.9%; P=0.30). Compared to those who received combined therapy, patients with medical therapy alone were most likely to receive cephalosporin (72.1% vs. 41.2%; P=< 0.0001), vancomycin (23% vs. 12.4%; P=0.047) and metronidazole (27.9% vs. 14.7%; P=0.022). In both groups, median duration of antimicrobial therapy was 42 days (P=0.12). Patients with medical therapy alone had a higher mortality rate (18% vs. 7.1%; p=0.014) but less neurologic sequelae (21.3% vs. 30.6%; P=0.16) compared with combined therapy. Medical Management. Organism isolated in the medical management group Combined Management. Organism isolated in the combined management group Demographic and Clinical Characteristics of Patients with Brain Abscess who Underwent Therapeutic Management Conclusion Most patients with pyogenic brain abscess had no identified risk factors, and brain MRI and cranial CT were the diagnostic imaging modalities of choice. Compared to those who received medical therapy alone, patients with combined treatment had a single and greater size fluid collection with the presence of midline shift. A prompt combined surgical and medical approach with prolonged antimicrobial therapy can cure the infection. Outcomes of Patients with Bacterial Brain Abscess Radiologic and Surgical Diagnosis of Patient with Brain Abscess who Underwent Therapeutic Management Disclosures John C. O’Horo, Sr., MD, MPH, Bates College and Elsevier Inc (Consultant) M. Rizwan Sohail, MD, Medtronic Inc., Philips, and Aziyo Biologics, Inc (Consultant) M. Rizwan Sohail, MD, Aziyo Biologics (Individual(s) Involved: Self): Consultant; Philips (Individual(s) Involved: Self): Consultant