Umbravirus-like RNA viruses are capable of independent systemic plant infection in the absence of encoded movement proteins.

The signature feature of all plant viruses is the encoding of movement proteins (MPs) that supports the movement of the viral genome into adjacent cells and through the vascular system. The recent discovery of umbravirus-like viruses (ULVs), some of which only encode replication-associated proteins, suggested that they, as with umbraviruses that lack encoded capsid proteins (CPs) and silencing suppressors, would require association with a helper virus to complete an infection cycle. We examined the infection properties of 2 ULVs: citrus yellow vein associated virus 1 (CY1), which only encodes replication proteins, and closely related CY2 from hemp, which encodes an additional protein (ORF5CY2) that was assumed to be an MP. We report that both CY1 and CY2 can independently infect the model plant Nicotiana benthamiana in a phloem-limited fashion when delivered by agroinfiltration. Unlike encoded MPs, ORF5CY2 was dispensable for infection of CY2, but was associated with faster symptom development. Examination of ORF5CY2 revealed features more similar to luteoviruses/poleroviruses/sobemovirus CPs than to 30K class MPs, which all share a similar single jelly-roll domain. In addition, only CY2-infected plants contained virus-like particles (VLPs) associated with CY2 RNA and ORF5CY2. CY1 RNA and a defective (D)-RNA that arises during infection interacted with host protein phloem protein 2 (PP2) in vitro and in vivo, and formed a high molecular weight complex with sap proteins in vitro that was partially resistant to RNase treatment. When CY1 was used as a virus-induced gene silencing (VIGS) vector to target PP2 transcripts, CY1 accumulation was reduced in systemic leaves, supporting the usage of PP2 for systemic movement. ULVs are therefore the first plant viruses encoding replication and CPs but no MPs, and whose systemic movement relies on a host MP. This explains the lack of discernable helper viruses in many ULV-infected plants and evokes comparisons with the initial viruses transferred into plants that must have similarly required host proteins for movement.

Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer.

BACKGROUND: The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy. METHODS: We conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions. RESULTS: From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval [CI], 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group. CONCLUSIONS: In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others; CALGB 140503 ClinicalTrials.gov number, NCT00499330.).

Epigenetic therapy inhibits metastases by disrupting premetastatic niches.

Cancer recurrence after surgery remains an unresolved clinical problem1-3. Myeloid cells derived from bone marrow contribute to the formation of the premetastatic microenvironment, which is required for disseminating tumour cells to engraft distant sites4-6. There are currently no effective interventions that prevent the formation of the premetastatic microenvironment6,7. Here we show that, after surgical removal of primary lung, breast and oesophageal cancers, low-dose adjuvant epigenetic therapy disrupts the premetastatic microenvironment and inhibits both the formation and growth of lung metastases through its selective effect on myeloid-derived suppressor cells (MDSCs). In mouse models of pulmonary metastases, MDSCs are key factors in the formation of the premetastatic microenvironment after resection of primary tumours. Adjuvant epigenetic therapy that uses low-dose DNA methyltransferase and histone deacetylase inhibitors, 5-azacytidine and entinostat, disrupts the premetastatic niche by inhibiting the trafficking of MDSCs through the downregulation of CCR2 and CXCR2, and by promoting MDSC differentiation into a more-interstitial macrophage-like phenotype. A decreased accumulation of MDSCs in the premetastatic lung produces longer periods of disease-free survival and increased overall survival, compared with chemotherapy. Our data demonstrate that, even after removal of the primary tumour, MDSCs contribute to the development of premetastatic niches and settlement of residual tumour cells. A combination of low-dose adjuvant epigenetic modifiers that disrupts this premetastatic microenvironment and inhibits metastases may permit an adjuvant approach to cancer therapy.

Surgery and Surgical Training Prior to Graduate Medical Education: A Blue Ribbon Committee II, Medical Student Education Subcommittee Report.

OBJECTIVE: To update and add to the first report commissioned by the Blue Ribbon Committee about 20 years prior. SUMMARY OF BACKGROUND DATA: Following a summit in late 2022 commissioned by the American Board of Surgery regarding competency-based reforms in surgical education and via a partnership with the American College of Surgeons (ACS) and other stakeholders, a Blue Ribbon Committee (BRC-II) on surgical education was formed. The BRC-II would have seven subcommittees. This paper details the work of the Medical Student Subcommittee within the BRC- II. METHODS: The subcommittee's work, supported by staff from the ACS, entailed a thorough literature review, which involved collating and aggregating the findings, identifying key challenges and opportunities, and committing to draft recommendations. These recommendations were then presented and refined via discussions with the Blue Ribbon Committee at large in multiple virtual and in-person settings. RESULTS: The subcommittee's work is detailed below and further summarized in table format. The section below elucidates the medical student education continuum and discusses the pertinent topics of recruitment, surgical engagement in medical student training and the surgical image, training for the current surgical practice model, trainee selection for graduate medical education (GME), and optimizing the transition from undergraduate medical education (UME) to GME. CONCLUSIONS: The last two decades have shown significant changes and shifts in medical education and surgical practice. The findings of BRC-II in this manuscript help to structure the current and future necessary improvements, focusing on different aspects of medical student education.

Role of Phenylethanolamine-N-methyltransferase on Nicotine-Induced Vasodilation in Rat Cerebral Arteries.

OBJECTIVE: The sympathetic-parasympathetic (or axo-axonal) interaction mechanism mediated that neurogenic relaxation, which was dependent on norepinephrine (NE) releases from sympathetic nerve terminal and acts on ß2-adrenoceptor of parasympathetic nerve terminal, has been reported. As NE is a weak ß2-adrenoceptor agonist, there is a possibility that synaptic NE is converted to epinephrine by phenylethanolamine-N-methyltransferase (PNMT) and then acts on the ß2-adrenoceptors to induce neurogenic vasodilation. METHODS: Blood vessel myography technique was used to measure relaxation and contraction responses of isolated basilar arterial rings of rats. RESULTS: Nicotine-induced relaxation was sensitive to propranolol, guanethidine (an adrenergic neuronal blocker), and Nω-nitro-l-arginine. Nicotine- and exogenous NE-induced vasorelaxation was partially inhibited by LY-78335 (a PNMT inhibitor), and transmural nerve stimulation depolarized the nitrergic nerve terminal directly and was not inhibited by LY-78335; it then induced the release of nitric oxide (NO). Epinephrine-induced vasorelaxation was not affected by LY-78335. However, these vasorelaxations were completely inhibited by atenolol (a ß1-adrenoceptor antagonist) combined with ICI-118,551 (a ß2-adrenoceptor antagonist). CONCLUSIONS: These results suggest that NE may be methylated by PNMT to form epinephrine and cause the release of NO and vasodilation. These results provide further evidence supporting the physiological significance of the axo-axonal interaction mechanism in regulating brainstem vascular tone.

NCCN Guidelines® Insights: Mesothelioma: Pleural, Version 1.2024.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.

Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.

Normal postvoid residual urine in healthy adults.

OBJECTIVE: To establish a normal reference value of postvoid residual (PVR) urine volume in "healthy" adults. METHODS: Adults were recruited to undergo uroflowmetry and PVR. Those with neurological disorders, malignancy, diabetes, known lower urinary tract dysfunction, and urinary tract infection within the previous 3 months, were excluded from the study. Constipation was defined as Rome IV ≥ 2. RESULTS: Of the 883 adults enrolled in this study, 194 (22.3%) did not complete the questionnaires or perform the uroflowmetry, 103 (11.7%) met ≥1 exclusion criteria and thus were excluded. In addition, 30 and 38 uroflowmetry were excluded due to artifacts and low bladder volume (BV) (<100 mL), respectively. Finally, 515 uroflowmetry and PVR data from adults aged 36-89 (mean: 59.0 ± 9.5) were examined. There was a significant nonlinear relationship between BV and PVR (p < 0.05), with PVR significantly increased when BV was around 528 mL. Women had lower PVR than men (p < 0.05). PVR also increased as the International Prostatic Symptom Score (IPSS) increased. PVR was unaffected by age and functional constipation. A multivariate analysis revealed that BV (p < 0.05) and IPSS (p < 0.05) had significant influence on PVR, but age, gender, and Rome IV score did not. The 90th and 95th percentiles of PVR for men were 73.2 mL (25% of BV) and 102.6 mL (30% of BV), respectively, while for women they were 60.5 mL (21% of BV) and 93.8 mL (27% of BV), respectively. CONCLUSION: Women had lower PVR than men. The 90th percentile or 95th percentile of normal adults' PVR may serve as the upper limit of normal PVR, and readings above this level may necessitate additional evaluation and treatment. Further studies are required to substantiate these recommendations.

Superficial parasternal intercostal plane blocks in cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Traditional multimodal analgesic strategies have several contraindications in cardiac surgery patients, forcing clinicians to use alternative options. Superficial parasternal intercostal plane blocks, anesthetizing the anterior cutaneous branches of the thoracic intercostal nerves, are being explored as a straightforward method to treat pain after sternotomy. We sought to evaluate the literature on the effects of superficial parasternal blocks on pain control after cardiac surgery. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched MEDLINE, Embase, CENTRAL, and Web of Science databases for RCTs evaluating superficial parasternal intercostal plane blocks in adult patients undergoing cardiac surgery via midline sternotomy published from inception to 11 March 2022. The prespecified primary outcome was opioid consumption at 12 hr. The risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool, and the quality of evidence was evaluated using the grading of recommendations, assessments, development, and evaluations. Outcomes were analyzed with a random-effects model. All subgroups were prespecified. RESULTS: We reviewed 1,275 citations. Eleven RCTs, comprising 756 patients, fulfilled the inclusion criteria. Only one study reported the prespecified primary outcome, precluding the possibility of meta-analysis. This study reported a reduction in opioid consumption (-11.2 mg iv morphine equivalents; 95% confidence interval [CI], -8.2 to -14.1) There was a reduction in opioid consumption at 24 hr (-7.2 mg iv morphine equivalents; 95% CI, -5.6 to -8.7; five trials; 436 participants; moderate certainty evidence). All five studies measuring complications reported that none were detected, which included a sample of 196 blocks. CONCLUSION: The literature suggests a potential benefit of using superficial parasternal blocks to improve acute postoperative pain control after cardiac surgery via midline sternotomy. Future studies specifying dosing regimens and adjuncts are required. STUDY REGISTRATION: PROSPERO (CRD42022306914); first submitted 22 March 2022.

RéSUMé: OBJECTIF: Il existe plusieurs contre-indications aux stratégies analgésiques multimodales traditionnelles chez la patientèle de chirurgie cardiaque, ce qui oblige les clinicien·nes à se tourner vers d'autres options. Les blocs des plans intercostaux parasternaux superficiels, anesthésiant les branches cutanées antérieures des nerfs intercostaux thoraciques, sont l'une des méthodes simples actuellement explorées pour traiter la douleur après une sternotomie. Nous avons cherché à évaluer la littérature sur les effets des blocs parasternaux superficiels sur le contrôle de la douleur après une chirurgie cardiaque. MéTHODE: Nous avons réalisé une revue systématique et une méta-analyse des études randomisées contrôlées (ERC). Nous avons fait des recherches dans les bases de données MEDLINE, Embase, CENTRAL et Web of Science pour en tirer les ERC évaluant les blocs des plans intercostaux parasternaux superficiels chez les patient·es adultes bénéficiant d'une chirurgie cardiaque par sternotomie médiane publiées depuis leur création jusqu'au 11 mars 2022. Le critère d'évaluation principal préspécifié était la consommation d'opioïdes à 12 heures. Le risque de biais a été évalué à l'aide de l'outil Cochrane Collaboration Risk of Bias, et la qualité des données probantes à l'aide de l'outil GRADE. Les résultats ont été analysés à l'aide d'un modèle à effets aléatoires. Tous les sous-groupes étaient préspécifiés. RéSULTATS: Nous avons examiné 1275 citations. Onze ERC, comprenant 756 patient·es, remplissaient les critères d'inclusion. Une seule étude a rapporté le critère d'évaluation principal préspécifié, ce qui a exclu la possibilité d'une méta-analyse. Cette étude a rapporté une réduction de la consommation d'opioïdes (−11,2 mg équivalents de morphine iv; intervalle de confiance [IC] à 95 %, −8,2 à −14,1). Il y a eu une réduction de la consommation d'opioïdes à 24 heures (−7,2 mg équivalents de morphine iv; IC 95 %, −5,6 à −8,7; cinq études; 436 participant·es; données probantes de certitude modérée). Les cinq études mesurant les complications ont rapporté qu'aucune complication n'avait été détectée, en incluant un échantillon de 196 blocs. CONCLUSION: La littérature suggère un avantage potentiel de l'utilisation de blocs parasternaux superficiels pour améliorer le contrôle de la douleur postopératoire aiguë après une chirurgie cardiaque par sternotomie médiane. Des études futures précisant les schémas posologiques et les adjuvants sont nécessaires. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022306914); soumis pour la première fois le 22 mars 2022.

Methyl Palmitate Modulated NMDA-Induced Cerebral Hyperemia in Hypertensive Rats.

N-methyl-D-aspartate (NMDA) receptors were found to be dysfunctional in hypertensive rats. Methyl palmitate (MP) has been shown to diminish the nicotine-induced increase in blood flow in the brainstem. The aim of this study was to determine how MP modulated NMDA-induced increased regional cerebral blood flow (rCBF) in normotensive (WKY), spontaneously hypertensive (SHR), and renovascular hypertensive (RHR) rats. The increase in rCBF after the topical application of experimental drugs was measured using laser Doppler flowmetry. Topical NMDA application induced an MK-801-sensitive increase in rCBF in anesthetized WKY rats, which was inhibited by MP pretreatments. This inhibition was prevented by pretreatment with chelerythrine (a PKC inhibitor). The NMDA-induced increase in rCBF was also inhibited by the PKC activator in a concentration-dependent manner. Neither MP nor MK-801 affected the increase in rCBF induced by the topical application of acetylcholine or sodium nitroprusside. Topical application of MP to the parietal cortex of SHRs, on the other hand, increased basal rCBF slightly but significantly. MP enhanced the NMDA-induced increase in rCBF in SHRs and RHRs. These results suggested that MP had a dual effect on the modulation of rCBF. MP appears to play a significant physiological role in CBF regulation.

A systematic review of paediatric neurogenic lower urinary tract dysfunction guidelines using the Appraisal of Guidelines and Research Evaluation (AGREE) II instrument.

OBJECTIVE: To examine and critique current international clinical practice guidelines (CPGs) on management of paediatric neurogenic lower urinary tract dysfunction (NLUTD) and assess the applicability of these guidelines to clinical practice. MATERIALS AND METHODS: We conducted a systematic review of all CPGs on NLUTD published in English from the year 2010 to 2022. Six reviewers independently used the Appraisal of Guidelines and Research Evaluation (AGREE) II instrument to appraise all eligible CPGs. This instrument is comprised of 23 items organised into six quality domains. The scores for each item and domain were tabulated for each reviewer and interrater reliability was assessed for each domain using the intraclass correlation coefficient (ICC). RESULTS: Six CPGs were appraised and these included: National Institute for Health and Care Excellence (NICE), European Society for Paediatric Urology, International Children's Continence Society, Irish, Spina Bifida Association (SBA), and International Brazilian Journal of Urology guidelines. They had high mean standardised scores in the domain on 'scope and purpose' and 'clarity of presentation' but had low scores in the domain of 'applicability'. The top three CPGs based on overall score were the NICE, Irish and SBA guidelines and the reviewers had high degree of interrater reliability (ICC 0.912, P < 0.001). The mean scores in various domains for the top three guidelines were 95.8 (scope and purpose), 87.5 (stakeholder involvement), 69.1 (rigour of development), 94.0 (clarity of presentation), 68.4 (applicability), and 59.7 (editorial independence). The diagnostic and treatment recommendations of the top three guidelines were presented. CONCLUSION: The existing CPGs on paediatric NLUTD provide high-quality evidence based recommendations. The NICE, Irish and SBA guidelines were the top three CPGs identified. They scored high on most domains except applicability and editorial independence. These domains need to be considered for future updates to improve the utility.

Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.

NCCN Guidelines® Insights: Non-Small Cell Lung Cancer, Version 2.2023.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.

Relationship between sexual and bladder dysfunction in women consuming ketamine.

BACKGROUND: Although ketamine has become the second most popular recreational drug in Taiwan, there have been very few reported studies that investigated female sexual dysfunction (FSD) in ketamine abusers (KAs). AIMS: We sought to compare the difference between street and hospital KAs and explored the risk factors for FSD and lower urinary tract symptoms (LUTS) in KAs. METHODS: In this cross-sectional study, female KAs aged 18 years or older were invited to complete anonymous questionnaires during an educational course provided by the departments of substance control and prevention of the local government or under the instruction of medical providers at a urology clinic. Data were reported as median (IQR) and OR and analyzed with commercial statistical software. OUTCOMES: Key outcome measurements were illicit drug use history, FSD symptoms, and LUTS severity. RESULTS: We included 139 women (104 street and 35 hospital KAs) with a median age of 27.08 years. FSD was reported in 76% of all the participants (street vs hospital KAs, 68% vs 97%, P < 0.001). LUTS (Interstitial Cystitis Symptom Index [ICSI] + Interstitial Cystitis Problem Index [ICPI] ≥12) was found to be a significant risk factor for FSD in KAs. More hospital KAs (71%) reported experiencing LUTS (ICSI + ICPI ≥12) than street KAs (8%, P < 0.001). Longer duration of ketamine use (≥36 months) and mild to severe psychological symptoms (5-item Brief Symptom Rating Scale [BSRS-5] ≥6) were significant risk factors for LUTS. CLINICAL IMPLICATIONS: Sexual problems among KAs should not be overlooked since more severe sexual dysfunction was observed in patients reporting LUTS. STRENGTHS AND LIMITATIONS: To our knowledge, the present study is the largest study using validated and reliable questionnaires to examine FSD in KAs and also the first study to include street KAs. The main limitation of this study is using self-report questionnaires as they are subjective and susceptible to human errors and recall biases. CONCLUSIONS: Women who abused ketamine and reported experiencing LUTS were found to be more likely to have FSD.

The COVID-19 Era Is Associated With Delays in Esophageal Cancer Diagnosis and Treatment.

INTRODUCTION: The coronavirus disease-2019 (COVID-19) pandemic has substantially affected the delivery of healthcare globally. The purpose of this study was to evaluate the association of this era with the timeline of care in esophageal cancer patients. METHODS: We performed a retrospective chart-review of patients presenting to a single high-volume tertiary care center with the diagnosis of esophageal cancer. COVID era was defined as March 2020-December 2020 and compared with the year before (3/2019-12/2019). RESULTS: In total, 117 patients presented in the COVID-era versus 190 in pre-COVID. Stage 3 + 4 disease was found in 77.8% of the patients in the COVID-era compared to 68.9% in the pre-COVID era (P = 0.34). Diagnoses through emergency department admission were 35.5% in the COVID versus 26.7% in the pre-COVID group (P = 0.15). In the COVID era it took a median of 78 d to visit primary care provider (versus 52 d, P = 0.12 in pre-COVID), 45 d to endoscopy (versus 18 d, P = 0.004) and 38 d to treatment initiation (versus 36 d, P = 0.48). Thirty-five percent of the patients underwent esophagectomy compared to 26% in the pre-COVID-era. Median days of intensive-care-unit (ICU) (2 versus 3, P = 0.16) and hospital stay (14 versus 15, P = 0.28) were similar in both groups as well as postoperative 30-day morbidities (63 versus 63%, P = 0.48). One-year follow-up showed 83.7% (95% confidence interval [CI]: 73.8%-90.1%) survival in the COVID-group compared to 76.4% (95% CI: 66.9%-83.5%) in the pre-COVID-group (P = 0.58). Only three patients had a positive COVID result. CONCLUSIONS: Our institution treated fewer esophageal cancer patients during COVID-19 accompanied by a delay in endoscopic diagnosis. Postoperative outcomes and 1-year survival remained similar.

External validation of the ISARIC 4C Mortality Score to predict in-hospital mortality among patients with COVID-19 in a Canadian intensive care unit: a single-centre historical cohort study.

PURPOSE: With uncertain prognostic utility of existing predictive scoring systems for COVID-19-related illness, the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) 4C Mortality Score was developed by the International Severe Acute Respiratory and Emerging Infection Consortium as a COVID-19 mortality prediction tool. We sought to externally validate this score among critically ill patients admitted to an intensive care unit (ICU) with COVID-19 and compare its discrimination characteristics to that of the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores. METHODS: We enrolled all consecutive patients admitted with COVID-19-associated respiratory failure between 5 March 2020 and 5 March 2022 to our university-affiliated and intensivist-staffed ICU (Jewish General Hospital, Montreal, QC, Canada). After data abstraction, our primary outcome of in-hospital mortality was evaluated with an objective of determining the discriminative properties of the ISARIC 4C Mortality Score, using the area under the curve of a logistic regression model. RESULTS: A total of 429 patients were included, 102 (23.8%) of whom died in hospital. The receiver operator curve of the ISARIC 4C Mortality Score had an area under the curve of 0.762 (95% confidence interval [CI], 0.717 to 0.811), whereas those of the SOFA and APACHE II scores were 0.705 (95% CI, 0.648 to 0.761) and 0.722 (95% CI, 0.667 to 0.777), respectively. CONCLUSIONS: The ISARIC 4C Mortality Score is a tool that had a good predictive performance for in-hospital mortality in a cohort of patients with COVID-19 admitted to an ICU for respiratory failure. Our results suggest a good external validity of the 4C score when applied to a more severely ill population.

RéSUMé: OBJECTIF: Compte tenu de l'utilité pronostique incertaine des systèmes de notation prédictive existants pour les maladies liées à la COVID-19, le score de mortalité ISARIC 4C a été mis au point par l'International Severe Acute Respiratory and Emerging Infection Consortium en tant qu'outil de prédiction de la mortalité associée à la COVID-19. Nous avons cherché à valider en externe ce score chez les patient·es gravement malades atteint·es de COVID-19 admis·es dans une unité de soins intensifs (USI) et à comparer ses caractéristiques de discrimination à celles des scores APACHE II (Acute Physiology and Chronic Health Evaluation) et SOFA (Sequential Organ Failure Assessment). MéTHODE: Nous avons recruté toutes les personnes consécutives admises pour insuffisance respiratoire associée à la COVID-19 entre le 5 mars 2020 et le 5 mars 2022 dans notre unité de soins intensifs affiliée à l'université et dotée d'intensivistes (Hôpital général juif, Montréal, QC, Canada). Après l'abstraction des données, notre critère d'évaluation principal de mortalité à l'hôpital a été évalué dans le but de déterminer les propriétés discriminatives du score de mortalité ISARIC 4C, en utilisant la surface sous la courbe d'un modèle de régression logistique. RéSULTATS: Au total, 429 patient·es ont été inclus·es, dont 102 (23,8 %) sont décédé·es à l'hôpital. La fonction d'efficacité du récepteur (courbe ROC) du score de mortalité ISARIC 4C avait une surface sous la courbe de 0,762 (intervalle de confiance [IC] à 95 %, 0,717 à 0,811), tandis que celles des scores SOFA et APACHE II étaient de 0,705 (IC 95%, 0,648 à 0,761) et 0,722 (IC 95%, 0,667 à 0,777), respectivement. CONCLUSION: Le score de mortalité ISARIC 4C est un outil qui a affiché une bonne performance prédictive de la mortalité à l'hôpital dans une cohorte de patient·es atteint·es de COVID-19 admis·es dans une unité de soins intensifs pour insuffisance respiratoire. Nos résultats suggèrent une bonne validité externe du score 4C lorsqu'il est appliqué à une population plus gravement malade.

Echocardiography findings in amniotic fluid embolism: a systematic review of the literature.

PURPOSE: Amniotic fluid embolism (AFE) is a leading cause of obstetrical cardiac arrest and maternal morbidity. The pathogenesis of hemodynamic collapse is thought to be from right ventricular (RV) failure; however, there is a paucity of data documenting echocardiography findings in this population. We undertook a systematic review of the literature to evaluate the echocardiography findings in patients with AFE. SOURCES: We retrieved all case reports and case series reporting AFE in Embase and MEDLINE from inception to 20 November 2021. Studies reporting AFE diagnosed by fulfilling at least one of three different proposed AFE criteria and echocardiography findings during hospitalization were included. Patient and echocardiographic data were retrieved, and univariate logistic regression analysis was performed for outcomes of interest. Bias was assessed using the Joanna Briggs Institute clinical appraisal tool for case series. PRINCIPAL FINDINGS: Eighty publications reporting on 84 patients were included in the final review. Fifty-five out of 82 patients with data (67%) showed RV dysfunction, including 11/82 (13%) with biventricular dysfunction; 14/82 (17%) had normal systolic function. No data on RV or left ventricular function were reported for two patients. The presence of RV dysfunction on echocardiography was associated with cardiac arrest (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.39 to 9.67; P = 0.009), and a composite risk of cardiac arrest, maternal death or use of extracorporeal membrane oxygenation (OR, 3.86; 95% CI, 1.43 to 10.4; P = 0.007). A low risk of bias was observed in 15/84 (18%) cases. CONCLUSIONS: Right ventricular dysfunction on echocardiography is a common finding in AFE and is associated with a high risk of cardiac arrest. The finding of RV dysfunction on echocardiography may help diagnose AFE and help triage the highest risk patients with AFE. STUDY REGISTRATION: PROSPERO (CRD42021271323); registered 1 September 2021.

RéSUMé: OBJECTIF: L'embolie amniotique (EA) est l'une des principales causes d'arrêt cardiaque obstétrical et de morbidité maternelle. Il est présumé que la pathogenèse du choc hémodynamique provient d'une défaillance ventriculaire droite (VD). Cependant, il y a peu de données documentant les constatations de l'examen échocardiographique dans cette population. Nous avons effectué une revue systématique des données probantes visant à évaluer l'utilité de l'échocardiographie chez les patientes atteintes d'embolie amniotique. SOURCES: Nous avons évalué tous les rapports de cas et séries de cas rapportant une EA dans les bases de données Embase et MEDLINE de leur création jusqu'au 20 novembre 2021. Les études rapportant une EA diagnostiquée en remplissant au moins l'un des trois critères d'EA proposés et les résultats échocardiographiques pendant l'hospitalisation ont été incluses. Les données sur les patientes et échocardiographiques ont été colligées, et une analyse de régression logistique univariée a été effectuée pour les issues cliniques d'intérêt. Le risque de biais a été évalué à l'aide de l'outil d'évaluation clinique de l'Institut Joanna Briggs pour les séries de cas. CONSTATATIONS PRINCIPALES: Quatre-vingts publications incluant 84 patientes ont été incluses dans la revue finale. Cinquante-cinq des 82 patientes présentant des données (67 %) avaient une dysfonction du VD incluant 11/82 (13 %) avec une dysfonction biventriculaire. Quatorze patientes sur 82 (17 %) avaient une fonction systolique normale. Aucune donnée sur la fonction du ventricule droit ou gauche n'a été rapportée pour deux patientes. La présence d'une dysfonction du VD à l'échocardiographie était associée à un arrêt cardiaque (rapport de cotes [RC], 3,66; intervalle de confiance à 95 % [IC], 1,39 à 9,67; P = 0,009), et à un risque composite d'arrêt cardiaque, de décès maternel ou d'utilisation de l'oxygénation par membrane extracorporelle (ECMO) (RC, 3,86; IC 95 %, 1,43 à 10,4; P = 0,007). Un faible risque de biais a été observé dans 15/84 (18 %) des cas. CONCLUSION: La dysfonction ventriculaire droite à l'échocardiographie est une constatation courante dans l'embolie amniotique et est associée à un risque élevé d'arrêt cardiaque. La découverte d'une dysfonction du VD à l'échocardiographie peut aider à diagnostiquer l'embolie amniotique et à identifier les patientes atteintes d'embolie amniotique les plus à risque. ENREGISTREMENT DE L'éTUD: PROSPERO (CRD42021271323); enregistrée le 1er septembre 2021.

Is Female Representation Increasing in Society and Journal Editorial Boards in Oral and Maxillofacial Surgery?

PURPOSE: Surgical specialties, including oral and maxillofacial surgery (OMS), are traditionally male-dominated fields. This study aimed to analyze the proportions of female surgeons on specialty society boards and journal editorial boards in OMS in the United States and to assess whether they were proportionate with female representation in OMS academic faculty between 2011 and 2020. METHODS: A retrospective cohort study was performed using information obtained from the websites of two major OMS journals and information obtained directly from six American specialty societies for OMS. The predictor variable was time. The outcome variable was gender. Temporal changes in the proportion of women on society and journal editorial boards were compared with those amongst full-time board-certified faculty. Chi-squared test and simple linear regression were used for statistical analyses. RESULTS: Between 2011 and 2020, the proportion of women on editorial and society boards was 6.7% (31 women among 463 editorial board members) and 7.8% (43 women among 553 society board members), respectively. The proportion of women on editorial boards increased from 4.5% in 2011 to 10.6% in 2020 (ß = 0.656 [95% confidence interval, 0.336-0.975], P = .001) and that of women on society boards increased from 4.3% in 2011 to 10.3% in 2020 (ß = 0.645 [95% confidence interval, 0.252-1.037], P = .005). The proportion of women on editorial boards in 2011-2012 was significantly lower than that in full-time board-certified faculty positions (4.3% vs 11.0%, P = .045), whereas by 2019-2020, there was no difference between the 2 groups (9.8% vs 12.5%, P = .454). Similarly, the proportion of women on society boards in 2011-2012 tended to be lower than that in full-time board-certified faculty positions (5.6% vs 11.0%, P = .111), while in 2019-2020, no difference was observed between the 2 groups (10.4% vs 12.5%, P = .531). CONCLUSION: The proportion of women on society and journal editorial boards in OMS remains low but has progressively increased from 2011 to 2020, resulting in proportionate female representation in these positions compared with the gender composition of academic faculty in recent years. The current upward trend of female representation in leadership positions will hopefully present more diverse opportunities and mentorship/role models for trainees.

Mechanism of Social Stress-Related Erectile Dysfunction in Mice: Impaired Parasympathetic Neurotransmission and Ketamine.

This study aimed to investigate the mechanism underlying social stress (SS)-induced erectile dysfunction (ED) and evaluate the effects of a single subanesthetic dose of ketamine on SS-related ED. Male FVB mice were exposed to retired male C57BL/6 mice for 60 min daily over a 4-week period. In the third week, these FVB mice received intraperitoneal injections of either saline (SSS group) or ketamine (SSK group). Erectile function was assessed by measuring the intracavernosal pressure (ICP) during electrical stimulation of the major pelvic ganglia. Corpus cavernosum (CC) strips were utilized for wire myography to assess their reactivity. Both SSS and SSK mice exhibited significantly lower ICP in response to electrical stimulation than control mice. SS mice showed increased contractility of the CC induced by phenylephrine. Acetylcholine-induced relaxation was significantly reduced in SSS and SSK mice. Sodium nitroprusside-induced relaxation was higher in SSS mice compared to control and SSK mice. Nicotine-induced neurogenic and nitric oxide-dependent relaxation was significantly impaired in both SSS and SSK mice. An immunohistochemical analysis revealed co-localization of tyrosine hydroxylase and neuronal nitric oxide synthase-immunoreactive fibers in the CC. These findings highlight the complex nature of SS-related ED and suggest the limited efficacy of ketamine as a therapeutic intervention.

The Acute Effects and Mechanism of Ketamine on Nicotine-Induced Neurogenic Relaxation of the Corpus Cavernosum in Mice.

The present study aimed to investigate the acute effects and the mechanism of ketamine on nicotine-induced relaxation of the corpus cavernosum (CC) in mice. This study measured the intra-cavernosal pressure (ICP) of male C57BL/6 mice and the CC muscle activities using an organ bath wire myograph. Various drugs were used to investigate the mechanism of ketamine on nicotine-induced relaxation. Direct ketamine injection into the major pelvic ganglion (MPG) inhibited MPG-induced increases in ICP. D-serine/L-glutamate-induced relaxation of the CC was inhibited by MK-801 (N-methyl-D-aspartate (NMDA) receptor inhibitor), and nicotine-induced relaxation was enhanced by D-serine/L-glutamate. NMDA had no effect on CC relaxation. Nicotine-induced relaxation of the CC was suppressed by mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist), lidocaine, guanethidine (an adrenergic neuronal blocker), Nw-nitro-L-arginine (a non-selective nitric oxide synthase inhibitor), MK-801, and ketamine. This relaxation was almost completely inhibited in CC strips pretreated with 6-hydroxydopamine (a neurotoxic synthetic organic compound). Ketamine inhibited cavernosal nerve neurotransmission via direct action on the ganglion and impaired nicotine-induced CC relaxation. The relaxation of the CC was dependent on the interaction of the sympathetic and parasympathetic nerves, which may be mediated by the NMDA receptor.