Circ_002664/miR-182–5p/Herpud1 pathway importantly contributes to OGD/R-induced neuronal cell apoptosis

ObjectiveApoptosis is a prominent form of neuron death in cerebral ischemia-reperfusion-induced injury. Accompanied with the pathogenesis, Circ_002664 is upregulated. However, its role in the neuron apoptosis and the underlying mechanisms are unknown.MethodsIn this study, HT22 cells were treated with oxygen glucose deprivation and reoxygenation (OGD/R). The cell viability, apoptosis, proliferation and mitochondrial potential were examined. The expressions of interested genes, Circ_002664, miR-182–5p and Herpud1, were measured. The roles of these genes in OGD/R-induced cell injury were investigated by knockdown, overexpression alone or in combination. Additionally, the interactions between Circ_002664, miR-182–5p and Herpud1 were validated by luciferase report assay. The levels of MAP2, CHOP, Cytochrome C (CYC) and cleaved caspase-3 were determined.ResultsOGD/R treatment significantly increased cell apoptosis, decreased cell proliferation and mitochondrial potential, as well as increased Circ_002664 and Herpud1 expressions, and decreased miR-182–5p level. Circ_002664 knockdown markedly inhibited the effects by OGD/R on cell survival and altered expression of miR-182–5p and Herpud1. MiR-182–5p was observed sponged by Circ_002664 and negatively mediated its effect above mentioned, and this was by directly targeting Herpud1. Additionally, it was observed that CHOP expressions were regulated by Circ_002664/miR-182–5p/Herpud1 pathway, and in turn mediated its regulation in CYC and cleaved caspase-3.ConclusionsIn summary, our data showed that the Circ_002664 importantly contributed to neuronal cell apoptosis induced by OGD/R treatment, and this might be achieved by directly targeting miR-182–5p/Herpud1 pathway.     

miR-708 affords protective efficacy in anoxia/reoxygenation-stimulated cardiomyocytes by blocking the TLR4 signaling via targeting HMGB1

Ischemic heart disease is a proverbial and common cardiovascular disease, and constitutes a leading cause of disability and mortality globally. Myocardial ischemic/reperfusion (MI/R) injury is a highly orchestrated phenomenon that involves the excessive activation of high mobility group box 1 (HMGB1) signaling. In the present study, we sought to investigate the function of miR-708 in MI/R injury due to the predicted binding to HMGB1. Intriguingly, down-regulation of miR-708 and up-regulation of HMGB1 were observed in MI/R rat model and H9c2 cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. Dual luciferase reporter assays substantiated that HMGB1 was a direct target of miR-708. Moreover, miR-708 overexpression suppressed the mRNA and protein expression of HMGB1. Noticeably, elevation of miR-708 antagonized H/R-induced inhibition in cell viability; whilst, increased cell apoptosis evoked by H/R was restrained after miR-708 up-regulation. Simultaneously, miR-708 elevation suppressed H/R exposure-increased lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) generation, but elevated the activity of anti-oxidative stress superoxide dismutase (SOD). Additionally, H/R-increased production of pro-inflammatory cytokine TNF-α and IL-6 was offset following miR-708 overexpression. Moreover, enhancement of miR-708 inhibited H/R-evoked activation of the HMGB1-TLR4-NF-κB pathway by inhibiting the protein levels of HMGB1, TLR4 and p-p65 NF-κB. Specially, restoring this pathway offset the protective effects of miR-708 on H/R-induced cardiomyocyte injury. Together, these data indicate that miR-708 may protect against H/R-induced cardiomyocyte damage by directing targeting HMGB1 signaling, implying a promising therapeutic agent against ischemic heart disease including myocardial infarction.     

miR-101-3p and miR-199b-5p promote cell apoptosis in oral cancer by targeting BICC1

microRNAs (miRNAs) are involved in the carcinogenesis and progression of oral cancer. In this research, we aimed to identify the DE_miRNAs in oral cancer and the related molecular mechanisms. Using the GEO2R online tool, we identified 19 DE_miRNAs from the GSE115117 dataset and 3343 the DEGs from GSE74530 dataset. GO enrichment analysis of DE_miRNAs were performed using FunRich online analysis. Venn diagrams of the overlapping genes regulated by miR-204-5p, miR-199b-5p, and miR-101-3p were constructed using Draw Venn Diagram, FunRich, miRDB, TargetScan and GSE74530 databases. Cytoscape was used to construct a miRNAs-mRNAs network. RT-PCR and western blotting showed downregulation of miR-199b-5p and miR-101-3p, and upregulation of BICC1 in oral cancer cell lines and tissues. Spearman correlation analysis further demonstrated a positive correlation between miR-101-3p and miR-199b-5p levels and that miR-199b-5p and miR-101-3p were negatively correlated with BICC1 mRNA levels. miR-199b-5p and BICC1 were significantly related to survival rate of patients with oral cancer. Upregulation of miR-199b-5p and miR-101-3p inhibited the viability and promoted the apoptosis in TSCCA and SCC-9 cells, as shown by the CCK8 assay and flow cytometry analysis, respectively. Inhibition of BICC1 reduced viability and promoted apoptosis in TSCCA cells. Additionally, the relationship between BICC1 and both miR‐101-3p and miR-199b-5p was assessed by a luciferase reporter assay. The effects of miR-101-3p and miR-199b-5p upregulation on the promotion of cell apoptosis and the inhibition of tumor growth were reversed by overexpression of BICC1. In conclusion, the increased levels of miR-199b-5p and miR-101-3p enhanced apoptosis and suppressed cell viability in oral cancer by suppressing BICC1 expression.     

LINC00115 regulates lung adenocarcinoma progression via sponging miR-154-3p to modulate Sp3 expression

The most commonly diagnosed and most lethal subtype of lung cancer is lung adenocarcinoma (LUAD). Therefore, more detailed understanding of the potential mechanism and identification of potential targets of lung adenocarcinoma is needed. A growing number of reports reveals that long non-coding RNAs (lncRNAs) play crucial roles in cancer progression. In present study, we found that lncRNA LINC00115 was upregulated in LUAD tissues and cells. Functional studies revealed that LINC00115 knockdown inhibits the proliferation, growth, invasion, and migration of LUAD cells. Mechanically, we indicated that miR-154-3p is target microRNA of LINC00115, and the effect of downregulated LINC00115 on LUAD cells was partially reversed by the miR-154-3p antisense oligonucleotide (ASO-miR-154-3p). Further investigation revealed that Specificity protein 3 (Sp3) directly interacted with miR-154-3p, and the Sp3 level was positively correlated with the LINC00115 expression. Rescue experiments further showed that Sp3 overexpression partially restored the effect of downregulated LINC00115 on LUAD cells. Similarly, in vivo experiments confirmed that downregulated LINC00115 inhibited xenograft growth and Sp3 expression. Our results demonstrated that LINC00115 knockdown inhibited LUAD progression via sponging miR-154-3p to modulate Sp3 expression. These data indicate that the LINC00115/miR-154-3p/Sp3 axis can be a potential therapeutic target of LUAD.     

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

Establishment of reference intervals for thyroid hormones in premature infants beyond the first week of life using Beckman Coulter Unicel DxI 800

BackgroundThis 4-year retrospective cohort study aimed to establish reference intervals for free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) in premature infants using the Beckman Coulter Unicel DxI 800 automated immunoassay system.MethodsStudy subjects included 605 preterm infants with a gestational age of 26–36 weeks (corrected: 29–38 weeks). Pearson correlation was used to evaluate the association between hormone levels and gestational and corrected gestational ages. A nonparametric method was used to establish reference intervals based on corrected gestational age.ResultsFT3 and FT4 levels were positively correlated with gestational and corrected gestational ages, respectively. TSH levels were slightly negatively correlated with gestational and corrected gestational ages. FT3 significantly differed according to corrected gestational age (29–33 weeks vs 34–38 weeks); however, the difference was smaller than the reference change value (RCV) for the FT3 test. Thus, we combined the FT3 reference intervals into a single reference interval: 2.65–4.93 pmol/L (29–38 weeks). The reference intervals of FT4 and TSH were 11.20–24.97 pmol/L (29–38 weeks) and 1.01–10.14 mIU/L (29–38 weeks), respectively.ConclusionsUnlike those of full-term infants or adults, the reference intervals established in this study are applicable in premature infants. These results highlight the importance and complexity of establishing instrument-specific thyroid hormone reference intervals for preterm infants.     

The Female-Predominant Persistent Immune Dysregulation of the Post-COVID Syndrome

ObjectiveTo describe the clinical data from the first 108 patients seen in the Mayo Clinic post–COVID-19 care clinic (PCOCC).MethodsAfter Institutional Review Board approval, we reviewed the charts of the first 108 patients seen between January 19, 2021, and April 29, 2021, in the PCOCC and abstracted from the electronic medical record into a standardized database to facilitate analysis. Patients were grouped into phenotypes by expert review.ResultsMost of the patients seen in our clinic were female (75%; 81/108), and the median age at presentation was 46 years (interquartile range, 37 to 55 years). All had post-acute sequelae of SARS-CoV-2 infection, with 6 clinical phenotypes being identified: fatigue predominant (n=69), dyspnea predominant (n=23), myalgia predominant (n=6), orthostasis predominant (n=6), chest pain predominant (n=3), and headache predominant (n=1). The fatigue-predominant phenotype was more common in women, and the dyspnea-predominant phenotype was more common in men. Interleukin 6 (IL-6) was elevated in 61% of patients (69% of women; P=.0046), which was more common than elevation in C-reactive protein and erythrocyte sedimentation rate, identified in 17% and 20% of cases, respectively.ConclusionIn our PCOCC, we observed several distinct clinical phenotypes. Fatigue predominance was the most common presentation and was associated with elevated IL-6 levels and female sex. Dyspnea predominance was more common in men and was not associated with elevated IL-6 levels. IL-6 levels were more likely than erythrocyte sedimentation rate and C-reactive protein to be elevated in patients with post-acute sequelae of SARS-CoV-2 infection.     

Reductions in Cardiac Structure and Function 24 Months After Spinal Cord Injury: A Cross-Sectional Study

ObjectiveTo determine the alterations in cardiac structure and function that occur in the months after spinal cord injury (SCI).Study DesignCross-sectionalSettingRehabilitation HospitalParticipantsVolunteers (N=29; 4 women, 25 men) between 3 and 24 months after SCI.Main Outcome MeasuresTransthoracic echocardiography was performed on each volunteer. The relationships between time since injury and neurologic and sensory levels of injury to cardiac structure and function were assessed via multiple linear regression.ResultsTime since injury was most strongly associated with reductions in left ventricular end diastolic volume (r²=0.156; P=.034), end systolic volume (r²=0.141; P=.045), and mass (r²=0.138; P=.047). These structural changes were paralleled by reduced stroke volume (r²=0.143; P=.043) and cardiac output (r²=0.317; P=<.001). The reductions in left ventricular structure and systolic function were not differentially affected by neurologic or sensory levels of injury (P=.084-.921).ConclusionsThese results suggest progressive reductions in left ventricular structure and systolic function between 3 and 24 months after SCI that occur independent of neurologic and sensory levels of injury.     

Digital PCR detection of EGFR somatic mutations in non-small-cell lung cancer formalin fixed paraffin embedded samples

BackgroundDigital PCR (dPCR) is proposed to replace real time PCR and Sanger sequencing for detection and quantification of rare mutations, frequently unnoticed in the mass of tumoral cells. Screening of endothelial growth factor receptor (EGFR) mutations is mandatory before treatment with EGFR-targeted therapy with small-molecule tyrosine kinase inhibitors, which has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC).ObjectiveIn order to establish a cost-effective method for detection of mutations, we optimized dPCR identification of EGFR mutations in exons 18–21, and determined dPCR sensitivity, limits of detection (LoD) and quantification (LoQ).MethodsFor clinical validation, we compared the performance of dPCR and castPCR in 57 NSCL formalin fixed paraffin embedded samples and 10 lung cancer-free formalin fixed paraffin embedded samples.ResultsEGFR mutations DEL19, p.L858R, p.G719X, p.L861Q and p.T790 M were detected by dPCR in 27 samples versus 11 detected by castPCR (p = 0.014). LoD was determined as 100 molecules of DNA/uL and LoQ as 1%. Most of the samples (87%) identified by competitive Allele-Specific TaqMan (castPCR) as wild-type and by dPCR as mutated, presented less than 10% mutated DNA molecules (mean 4.57%). Accuracy of dPCR was 94.44%, as measured with the assay recommended by the College of American Pathologists.ConclusionThese results indicated higher sensibility and specificity of dPCR for screening EGFR mutations in NSCLC biopsies, compared to castPCR.     

Initiation of a Robotic Program in Spinal Surgery: Experience at a Three-Site Medical Center

ObjectiveTo highlight the early experience of implementing a robotic spine surgery program at a three-site medical center, evaluating the impact of increasing experience on the operative time and number of procedures performed.Patients and MethodsA retrospective chart review of patients undergoing robotic screw placement between September 4, 2018, and October 16, 2019, was conducted. Baseline characteristics as well as intraoperative and post-operative outcomes were obtained.ResultsFor a total of 77 patients, the mean age (SD) was 55.7 years (11.5) and 49.4% (n=38) were female. A total of 402 screws were placed (384 pedicle screws, 18 cortical screws) using robotic guidance with a median of two operative levels (interquartile range [IQR], 1 to 2). Median (IQR) estimated blood loss was 100 mL (50 to 200 mL) and the median (IQR) operative time was 224 minutes (193 to 307 minutes). With accrual of surgical experience, operative time declined significantly (R=-0.39; P<.001) whereas the number of procedures performed per week increased (R=0.30; P=.05) throughout the study period. Median (IQR) length of hospital stay following surgery was 2 days (IQR, 2 to 3 days). There were two screws requiring revision intraoperatively. No postoperative revisions were required, and no complications were encountered related to screw placement.ConclusionEarly experience at our institution using a spinal robot has demonstrated no requirement for postoperative screw revisions and no complications related to screw malposition. The increased operative times were reduced as the frequency of procedures increased. Moreover, procedural times diminished over a short period with a weekly increasing number of procedures.     

Cone Reconstruction for Ebstein Anomaly: Ventricular Remodeling and Preliminary Impact of Stem Cell Therapy

ObjectiveTo define the impact of tricuspid valve cone reconstruction (CR) on ventricular performance in Ebstein anomaly, both independently and after stem cell therapy.Patients and MethodsThe control group included 257 patients who had CR between June 2007 and December 2019. Ten subjects of a phase I stem cell therapy trial (May 2017 – March 2019) were compared with the controls to assess the echocardiographic impact on ventricular remodeling.ResultsAfter CR, right ventricular (RV) size decreased and left ventricular (LV) volume increased in all patients. Apical and biplane RV fractional area change (FAC) initially decreased, but rebounded by 6 months postoperation. Short-axis FAC increased early and was maintained at 6 months post-CR in the control group. At 6 months post-CR, cell therapy patients showed a significantly larger increase in short-axis FAC (24.4% vs 29.9%, P=.003). In addition, whereas LV ejection fraction (EF) was unchanged at 6 months post-CR in controls, cell therapy patients showed a significant increase in EF relative to baseline and to controls (55.6% vs 65.0%, P=.007).ConclusionCone reconstruction reduces tricuspid regurgitation and RV size, but is also associated with increased RV FAC and LV volume. Furthermore, injection of bone marrow–derived stem cells augmented the increase in RV FAC and was associated with improved LV EF at 6 months post-CR. This is evidence of a favorable interventricular interaction. These findings provide motivation for continued investigation into the potential benefits of stem cell therapy in Ebstein anomaly and other congenital cardiac malformations.Trial Registrationclinicaltrials.gov identifier: NCT02914171     

A Target Antigen–Based Approach to the Classification of Membranous Nephropathy

ObjectiveTo describe the clinical and pathological phenotype of membranous nephropathy (MN) associated with M-type-phospholipase–A₂-receptor (PLA₂R), thrombospondin-type-1-domain-containing-7A (THSD7A), semaphorin 3B (SEMA3B), neural-epidermal-growth-factor-like-1-protein (NELL-1), protocadherin 7 (PCDH7), exostosin 1/exostosin 2 (EXT1/EXT2) and neural cell adhesion molecule 1 (NCAM-1) as target antigens.MethodsA retrospective cohort of 270 adult patients with biopsy-proven MN diagnosed between January 2015 and April 2020 was classified as PLA₂R-, THSD7A-, SEMA3B-, NELL-1–, PCDH7-, EXT1/EXT2-, NCAM-1–associated or septuple-negative MN using serologic tests, immunostaining, and/or mass spectrometry. Clinical, biochemical, pathologic, and follow-up data were systematically abstracted from the medical records, including disease activity of conditions traditionally associated with MN and occurring within 5 years of MN diagnosis.ResultsPatients with PLA₂R-associated MN were predominantly middle-aged white men without associated disease. The presence of associated disease did not affect the clinical and pathologic characteristics of PLA₂R-associated MN, suggesting that they were coincidental rather than causally linked. THSD7A-, NELL-1–, PCDH7-, and NCAM-1–associated MN were rare and SEMA3B-associated MN was not discovered in our cohort. EXT1/EXT2-associated MN was primarily diagnosed in younger women with active systemic autoimmunity. A significant proportion of septuple-negative patients had associated malignancy or systemic autoimmunity.ConclusionThe widely used distinction between primary and secondary MN has limitations. We propose a refined terminology that combines the target antigen and associated disease to better classify MN and guide clinical decision making.     

A Prospective Longitudinal Study of Trajectories of Depressive Symptoms After Dysvascular Amputation

ObjectivesCharacterize the course of depressive symptoms during the first year after dysvascular amputation and identify factors that predict symptom trajectories.DesignProspective cohort study of individuals undergoing lower extremity amputation (LEA), surveyed at 4 time points (perioperative period, 6 weeks, 4 months, and 12 months postamputation). Multilevel modeling was used to describe and predict trajectories.SettingFour Veterans Affairs medical centers, a university hospital, and a level I trauma center.ParticipantsParticipants (N=141; 74% retention) were a consecutive sample, eligible if they were undergoing their first unilateral LEA secondary to dysvascular disease.InterventionsNot applicable.Main Outcome MeasurePatient Health Questionnaire-9.ResultsApproximately 40% of participants endorsed at least moderate depressive symptoms at perioperative baseline. Individuals with greater depressive symptoms in the perioperative period concurrently reported greater pain, poorer self-rated health, and prior mental health treatment. In the first 6 weeks after amputation there was a substantial improvement in depressive symptoms, especially among individuals with greater symptoms at baseline. Depressive symptoms were generally stable after 6 weeks. None of the covariates assessed significantly predicted trajectories of depressive symptom improvement.ConclusionsWatchful waiting may be the most appropriate course of action for many patients in the first 6 weeks after amputation. After 6 weeks, however, symptom levels tend to stabilize, suggesting that active intervention is called for if patients remain depressed at this point. Some patients may benefit from more proactive intervention, such as those with prior mental health treatment histories.     

Renin Production by Juxtaglomerular Cell Tumors and Clear Cell Renal Cell Carcinoma and the Role of Angiotensin Signaling Inhibitors

ObjectiveTo profile juxtaglomerular cell tumors (JXG) and histologic mimics by analyzing renin expression; to identify non-JXG renin-producing tumors in The Cancer Genome Atlas (TCGA) data sets; and to define the prevalence of hypertension (HTN) and patient outcomes with angiotensin signaling inhibitor (ASI) use in tumors of interest.Patients and MethodsThirteen JXGs and 10 glomus tumors (GTs), a histologic mimic, were evaluated for clinicopathologic features; TCGA data were analyzed to identify non-JXG renin-overexpressing tumors. An institutional registry was queried to determine the incidence of HTN, the use of ASIs in hypertensive patients, and the impact of ASIs on outcomes including progression-free survival (PFS) in a tumor type with high renin expression (clear cell renal cell carcinoma [CC-RCC] diagnosed between January 1, 2005, and December 31, 2012).ResultsWe found an association between renin production and HTN in JXG compared with GT. Analysis of TCGA data found that a subset of CC-RCCs overexpress renin relative to 29 other tumor types. Furthermore, analysis of our institutional registry revealed a high prevalence (64%) of HTN among 1203 patients treated with radical or partial nephrectomy for nonmetastatic CC-RCC. On multivariable Cox regression, patients with HTN treated with ASIs (34%) had improved PFS (hazard ratio, 0.76; 95% CI, 0.57 to 1.00; P=.05) compared with patients with HTN not treated with ASIs (30%).ConclusionThe identification of renin expression in a subset of CC-RCC may provide a biologic rationale for the high prevalence of HTN and improved PFS with ASI use in hypertensive patients with nonmetastatic CC-RCC.     

A Longitudinal Study Exploring Learning Environment Culture and Subsequent Risk of Burnout Among Resident Physicians Overall and by Gender

ObjectiveTo explore the relationship between learning environment culture and the subsequent risk of developing burnout in a national sample of residents overall and by gender.MethodsFrom April 7 to August 2, 2016, and May 26 to August 5, 2017, we surveyed residents in their second (R2) and third (R3) postgraduate year. The survey included a negative interpersonal experiences scale (score range 1 to 7 points, higher being worse) assessing psychological safety and bias, inclusion, respect, and justice; an unfair treatment scale (score range 1 to 5 points, higher being worse), and two items from the Maslach Burnout Inventory. Individual responses to the R2 and R3 surveys were linked.ResultsThe R2 survey was completed by 3588 of 4696 (76.4%) residents; 3058 of 3726 (82.1%) residents completed the R3 survey; and 2888 residents completed both surveys. Women reported more negative interpersonal experiences (mean [SD], 3.00 [0.83] vs 2.90 [0.85], P<.001) and unfair treatment (66.5% vs. 58.7%, P<.001) than men at R2. On multivariable analysis, women at R3 were more likely than their male counterparts to have burnout (odds ratio, 1.23; 95% CI, 1.02 to 1.48; P=.03). Both men and women who reported more negative interpersonal experiences at R2 were more likely to have burnout at R3 (odds ratio, 1.32; 95% CI, 1.14 to 1.52; P<.001). The factors contributing to burnout did not vary in effect magnitude by gender.ConclusionThese findings indicate women residents are more likely to have burnout relative to men in the third year of residency. Negative culture predicted subsequent burnout 1 year later among both men and women. Differences in burnout were at least partly due to differing levels of exposure to negative interactions for men versus women rather than a negative interaction having a differential impact on the well-being of men versus women.     

Robotic Mitral Valve Repair: Indication for Surgery Does Not Influence Early Outcomes

ObjectiveTo evaluate the outcomes of robotic mitral valve repair (MVr) by primary indication per American Heart Association guidelines for surgery: class I vs class IIa.Patients and MethodsFrom January 1, 2008, through September 30, 2016, 603 patients underwent robotic MVr for severe primary mitral regurgitation. Medical records of 576 consenting patients were retrospectively reviewed to determine the primary indication for surgery. Patients were stratified into class I or class IIa, and preoperative, intraoperative, and postoperative variables were compared.ResultsOf 516 patients, 428 (83%) had class I indication and 88 (17%) had class IIa indication for surgery. Preoperatively, no significant differences were observed between both cohorts. Importantly, a significantly higher number of patients with class I indication underwent MVr for bileaflet prolapse (172 of 428 [40%] vs 21 of 88 [25%]; P=.03). Early MVr outcomes indicated recurrent mitral regurgitation (moderate or greater) in only 12 of 576 (2%), and no significant differences were observed between classes (P=.23). Apart from parameters for ventricular size, all other intraoperative and postoperative variables were comparable between both cohorts.ConclusionComparable outcomes were indicated across all classes of indications for MVr surgery. These results continue to support the use of this surgical technique, even in less sick patients. Early referral along with more extensive robotic MVr experience will likely result in further improvements in long-term outcomes.     

Colleagues Meeting to Promote and Sustain Satisfaction (COMPASS) Groups for Physician Well-Being: A Randomized Clinical Trial

ObjectiveTo evaluate physician small groups to promote physician well-being in a scenario with provided discussion topics but without trained facilitators, and for which protected time was not provided but meal expenses were compensated.Participants and MethodsWe conducted a randomized controlled trial of 125 practicing physicians in the Department of Medicine, Mayo Clinic, Rochester, Minnesota, between October 2013 and October 2014 with subsequent assessment of organizational program implementation. Twelve biweekly self-facilitated discussion groups involving reflection, shared experience, and small-group learning took place over 6 months. Main outcome measures included meaning in work, burnout, symptoms of depression, quality of life, social support, and job satisfaction assessed using validated metrics.ResultsAt 6 months after completion of the intervention (12 months from baseline), the rate of overall burnout had decreased by 12.7% (31/62 to 19/51) in the intervention arm versus a 1.9% increase (25/61 to 24/56) in the control arm (P<.001). The rate of depressive symptoms had decreased by 12.8% (29/62 to 17/50) in the intervention arm versus a 1.1% increase (20/61 to 19/56) in the control arm (P<.001). The proportion of physicians endorsing at least moderate self-reported likelihood of leaving their current practice in the subsequent 2 years had decreased by 1.9% (17/62 to 13/51) in the intervention arm and increased by 6.1% (14/61 to 16/55) in the control arm (P<.001). No statistically significant differences were seen in mean changes in burnout scale scores, meaning, or social support, although numeric differences generally favored the intervention.ConclusionSelf-facilitated physician small-group meetings improved burnout, depressive symptoms, and job satisfaction. This intervention represents a low-cost strategy to promote important dimensions of physician well-being.Trial Registrationclinicaltrials.gov Identifier: NCT04466423     

Clinical Characteristics,Management Strategies and Outcomes of Acute Myocardial Infarction Patients With Prior Coronary Artery Bypass Grafting

ObjectiveTo investigate the management strategies, temporal trends, and clinical outcomes of patients with a history of coronary artery bypass graft (CABG) surgery and presenting with acute myocardial infarction (MI).Patients and MethodsWe undertook a retrospective cohort study using the National Inpatient Sample database from the United States (January 2004–September 2015), identified all inpatient MI admissions (7,250,768 records) and stratified according to history of CABG (group 1, CABG-naive [94%]; group 2, prior CABG [6%]).ResultsPatients in group 2 were older, less likely to be female, had more comorbidities, and were more likely to present with non-ST-elevation myocardial infarction compared with group 1. More patients underwent coronary angiography (68% vs 48%) and percutaneous coronary intervention (PCI) (44% vs 26%) in group 1 compared with group 2. Following multivariable logistic regression analyses, the adjusted odd ratio (OR) of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.98; 95% CI, 0.95 to 1.005; P=.11), all-cause mortality (OR, 1; 95% CI, 0.98 to 1.04; P=.6) and major bleeding (OR, 0.99; 95% CI, 0.94 to 1.03; P=.54) were similar to group 1. Lower adjusted odds of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.64; 95% CI, 0.57 to 0.72; P<.001), all-cause mortality (OR, 0.45; 95% CI, 0.38 to 0.53; P<.001), and acute ischemic stroke (OR, 0.71; 95% CI, 0.59 to 0.86; P<.001) were observed in group 2 patients who underwent PCI compared with those managed medically without any increased risk of major bleeding (OR, 1.08; 95% CI, 0.94 to 1.23; P=.26).ConclusionsIn this national cohort, MI patients with prior-CABG had a higher risk profile, but similar in-hospital adverse outcomes compared with CABG-naive patients. Prior-CABG patients who received PCI had better in-hospital clinical outcomes compared to those who received medical management.     

Immunological responses following the third dose of the BNT162b2 SARS-CoV-2 vaccine among Japanese healthcare workers

IntroductionA limited number of studies have shown a decline in antibody titers in healthcare workers beyond six months after the second dose of the BNT162b2 vaccine, and has been insufficiently investigated yet in the respective Asian ethnic groups.MethodsWe conducted a longitudinal observational study on 187 healthcare workers and other personnel and healthy adults at least eight months after vaccination at the International University of Health and Welfare.ResultsThe baseline (before the third dose of BNT162b2) anti-receptor binding domain (RBD) IgG level was 569[377–943] AU/mL 245[240–250] days after the second dose. The mean antibody titer of participants aged 20–29 years was 4.6 times higher than that of participants aged 70–79 years. After booster vaccination, serum anti-RBD antibody levels were elevated in all participants with a median titer of 23,250[14,612–33,401] AU/mL 21[19–23] days after the third dose. The median post-booster antibody titers in the 20–29, 30–39, 40–49, 50–59, 60–69, and 70–79 years age groups were 30.6, 33.0, 33.8, 27.4, 50.1, and 90.3 times, respectively, higher than the pre-booster ones. Antibody levels were 15% lower in daily drinkers compared to nondrinkers, suggesting that daily alcohol consumption can prevent antibody levels from increasing after vaccination. Our results show decreased antibody titers after two doses of the vaccine, especially in the elderly; however, the third dose of the vaccine resulted in a significant increase in antibody titers in all age groups.ConclusionsWe provided information on antibody responses following primary and booster doses of the BNT162b2 mRNA COVID-19 vaccine in Japan.