Procedural and cardiovascular outcomes of geriatric vs non-geriatric patients undergoing permanent pacemaker implantation - a nationwide cohort analysis.

BACKGROUND: Permanent pacemaker implantation is increasing exponentially to treat atrio-ventricular block and symptomatic bradyarrhythmia. Despite being a minor surgery, immediate complications such as pocket infection, pocket hematoma, pneumothorax, hemopericardium, and lead displacement do occur. METHODS: The Nationwide Inpatient Sample was queried from 2016 to 2018 to identify patients with pacemakers using ICD-10 procedure code. The Chi-square test was used for statistical analysis. RESULTS: The sample size consisted of 443,460 patients with a pacemaker, 26% were <70 years (male 57%, mean age of (60.6±9.7) yr, Caucasian 70%) and 74% were ≥70 years (male 50%, mean age of (81.4±5.9) yr, Caucasian 79%). Upon comparison of rates in the young vs elderly: mortality (1.6% vs 1.5%; P<0.01), obesity (26% vs 13%; P<0.001), coronary artery disease (40% vs 49%; P<0.001), HTN (74% vs 87%; P<0.01), anemia (4% vs 5%; P<0.01), atrial fibrillation (34% vs 49%; P<0.01), peripheral artery disease (1.7% vs 3%; P<0.01), CHF (31% vs 39%; P<0.001), diabetes (31% vs 27.4%; P<0.01), vascular complications (1.1% vs 1.2%; P<0.01), pocket hematoma (0.5% vs 0.8%; P<0.01), AKI (16% vs 21%; P<0.01), hemopericardium (0.1% vs 0.1%; P = 0.1), hemothorax (0.3% vs 0.2%; P<0.01), cardiac tamponade (0.4% vs 0.5%; P<0.01), pericardiocentesis (0.4% vs 0.4%; P<0.01), cardiogenic shock (4% vs 2.3%; P<0.01), respiratory complications (1.9% vs 0.9%; P<0.01), mechanical ventilation (5.1% vs 2.9%; P<0.01); post-op bleed (0.5% vs 0.3%; P<0.01), need for transfusion (4.8% vs 3.8%; P<0.01), severe sepsis (0.6% vs 0.5%; P<0.01 ), septic shock (2% vs 1%; P<0.01), bacteraemia (0.8% vs 0.4%; P<0.01), lead dislodgement (1.4% vs 1.1%; P<0.01). CONCLUSIONS: Our study revealed that the overall complication rates were lower in the elderly despite higher co-morbidities. This aligns with previous studies which showed lower rates in the elderly. Hence providers should not hesitate to provide guideline driven pacemaker placement in the elderly especially in patients with good life expectancy.

Cardiovascular outcomes of emergent vs elective transcatheter aortic valve replacement in severe aortic stenosis: regression matched meta-analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has been highly increased as the recommended option for patients with a high surgical risk. This study aims to commit a systematic review and meta-analysis to assess the outcomes in severe aortic stenosis patients following emergency transcatheter aortic valve replacement (emergent TAVR) compared to elective TAVR or eBAV followed by elective TAVR. METHODS: We conducted a systematic literature search of PubMed, Embase, Cochrane CENTRAL, CINAHL, Science Direct, and Google Scholar. We included nine studies in the latest analysis that reported the desired outcomes. Outcomes were classified into primary outcomes: 30-day all-cause mortality and 30-day readmission rate, and secondary outcomes, which were further divided into (a) peri-procedural outcomes, (b) vascular outcomes, and (c) renal outcomes. Statistical analysis was performed using Stata v.17 (College State, TX) software. RESULTS: A total of 44,731 patients with severe aortic stenosis were included (emergent TAVR n = 4502; control n = 40045). 30-day mortality was significantly higher in the emergent TAVR group (OR: 2.62; 95% CI = 1.76-3.92; P < 0.01). Regarding post-procedural outcomes, the length of stay was significantly higher in the emergent TAVR group (Hedges's g: +4.73 days; 95% CI = +3.35 to +6.11; P < 0.01). With respect to vascular outcomes, they were similar in both groups. Regarding renal outcomes, both acute kidney injury (OR: 2.52; 95% CI = 1.59-4.00; P < 0.01) and use of renal replacement therapy (OR: 2.33; 95% CI = 1.87-2.91; P < 0.01) were significantly higher in emergent TAVR group as compared to the control group. CONCLUSION: Our study demonstrated that despite increased 30-day mortality and worse renal outcomes, the post-procedural outcomes were similar in emergent and elective TAVR groups. The increased mortality and worse renal outcomes are likely due to hemodynamic instability in the emergent group. The similarity of post-procedural outcomes is evidence of the safety of TAVR even in emergent settings.

Mucosa-Associated Lymphoid Tissue Surgeries as a Possible Risk for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Background: Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal disorders that are caused by genetic susceptibility and environmental factors and affects a significant portion of the global population. The gut-associated lymphoid tissue (GALT) is known to play a crucial role in immune modulation and maintaining gut microbiota balance. Dysbiosis in the latter has a known link to IBD. Therefore, the increasing prevalence of adenoidectomy in children should be explored for its potential association with IBD. The objective of this paper was to assess the association between adenoid tissue removal and the risk of developing Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted a pooled meta-analysis to evaluate the extended clinical outcomes in patients who underwent appendicectomy and tonsillectomy compared to those who did not. Our approach involved systematically searching the PubMed database for relevant observational studies written in English. We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines to collect data from various time periods, and to address the diversity in study results; we employed a random-effects analysis that considered heterogeneity. For outcomes, odds ratios (ORs) were pooled using a random-effects model. Results: Seven studies, out of a total of 114,537, met our inclusion criteria. Our meta-analysis revealed a significant association between appendicectomy and CD (OR: 1.57; 95% confidence interval (CI): 1.01 - 2.43; heterogeneity I2 = 93%). Similarly, we found a significant association between tonsillectomy and CD (OR: 1.93; 95% CI: 0.96 - 3.89; I2 = 62%). However, no significant association was observed between appendicectomy and UC (OR: 0.60; 95% CI: 0.24 - 1.47; I2 = 96%), while a modest association was found between tonsillectomy and UC (OR: 1.24; 95% CI: 1.18 - 1.30; I2 = 0%). Conclusions: In summary, we found that the trend of appendicectomy is linked to higher odds of CD, and tonsillectomy is more likely associated with increased odds for both CD and UC, with a risk of bias present.

Myocardial Infarction in Chronic Myeloid Leukemia: Results from Nationwide Readmission Database.

Background and Objective Chronic myeloid leukemia (CML) is a hematological malignancy with an excellent prognostic outcome. After advancements in CML treatment and the introduction of different tyrosine kinase inhibitors (TKI), the life expectancy of CML patients has become equivalent to that of the general population. As a result, coronary artery disease is anticipated to be the leading cause of death among CML patients. Moreover, TKI use is associated with a risk of endothelial dysfunction, thrombosis, and cardiovascular events, including myocardial infarction. In this study, we compare the outcomes of percutaneous coronary intervention (PCI) in patients with CML to their matched non-CML counterparts. and compare the events reported with different TKI. Method The Nationwide Readmission Database (NRD) was searched from January 2016 to December 2020. for the study population. Adults of age ≥ 18 years with or without CML hospitalized for with a primary diagnosis of acute myocardial infarction, ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation myocardial infarction (NSTEMI) and underwent PCI were included. The patients were identified using ICD-10 codes. The baseline characteristics and outcomes of the CML and non-CML patients who underwent PCI were compared. The primary outcomes were in-hospital mortality and 30-day readmission rates. The secondary outcomes were the PCI complications rates. Data regarding TKI reports of STEMI and acute coronary syndrome were obtained from The FDA Adverse Event Reporting System (FARES). Results Out of 2,727,619 patients with myocardial infarction, 2,124 CML patients were identified. A total of 888 CML patients underwent PCI. The mean age was 68.34 ± 11.14, with 62.46 % above 65 years. The analysis showed no significant difference between CML and non-CML patients after PCI for death (OR? 0.93 (95% CI 0.49-1.80), P=0.527) and 30-day readmission (OR? 1.41 (95% CI 0.99-2.01), P=0.056) rates. CML patients were significantly older (mean age 68.34 ± 11.14 versus 64.40 ± 12.61, p < 0.001) than non-CML patients without a difference in sex distribution. Hypertension (85.45% versus 78.64%), diabetes (45.48% versus 37.29), stroke (11.84% versus 7.78) at baseline were significantly higher in CML group. Prior myocardial infarction events (20.51% versus 15.17%) and prior PCI procedure (24.47% versus 16.89%) were significantly higher in CML group. CML had a significantly longer hospital stay (4.66 ± 4.40 versus 3.75 ± 4.62 days, p = 0.001). The primary outcomes did not differ between the comparison groups. Conclusion This analysis showed no statistically significant difference in mortality, 30-day readmission, and complication rates post PCI between CML and non-CML patients. However, interestingly, CML patients may experience lower coronary artery dissection and ischemic stroke rates than those without CML diagnosis.

Impact of Social Vulnerability on Cardiac Arrest Mortality in the United States, 2016 to 2020.

BACKGROUND: Cardiac arrest is 1 of the leading causes of morbidity and mortality, with an estimated 340 000 out-of-hospital and 292 000 in-hospital cardiac arrest events per year in the United States. Survival rates are lower in certain racial and socioeconomic groups. METHODS AND RESULTS: We performed a county-level cross-sectional longitudinal study using the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research multiple causes of death data set between 2016 and 2020 among individuals of all ages whose death was attributed to cardiac arrest. The Social Vulnerability Index is a composite measure that includes socioeconomic vulnerability, household composition, disability, individuals from racial and ethnic minority groups status and language, and housing and transportation domains. We examined the impact of social determinants on cardiac arrest mortality stratified by age, race, ethnicity, and sex in the United States. All age-adjusted mortality rate (cardiac arrest AAMRs) are reported as per 100 000. Overall cardiac arrest AAMR during the study period was 95.6. The cardiac arrest AAMR was higher for men compared with women (119.6 versus 89.9) and for the Black population compared with the White population (150.4 versus 92.3). The cardiac arrest AAMR increased from 64.8 in counties in quintile 1 of Social Vulnerability Index to 141 in quintile 5, with an average increase of 13% (95% CI, 9.8%-16.9%) in AAMR per quintile increase. CONCLUSIONS: Mortality from cardiac arrest varies widely, with a >2-fold difference between the counties with the highest and lowest social vulnerability, highlighting the differential burden of cardiac arrest deaths throughout the United States based on social determinants of health.

Magnetic Resonance Imaging-based Prostate Cancer Screening in Carriers of Pathogenic Germline Mutations: Interim Results from the Initial Screening Round of the Prostate Cancer Genetic Risk Evaluation and Screening Study.

BACKGROUND: The risk of early-onset and clinically aggressive prostate cancer is elevated in carriers of certain rare pathogenic germline mutations. The utility of augmenting traditional prostate-specific antigen (PSA)-based screening measures with multiparametric magnetic resonance imaging (MRI) in this population is not yet known. OBJECTIVE: To evaluate MRI-based screening in comparison with traditional PSA-based screening among individuals at an elevated genetic risk for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Male germline carriers of pathogenic/likely pathogenic variants in any of 19 prostate cancer risk genes between the ages of 35 and 74 yr with no prior history of prostate cancer were recruited. Intervention Enrolled participants underwent screening with annual PSA, digital rectal examination (DRE), and triennial multiparametric MRI. Individuals with abnormal DRE, elevated age-adjusted PSA (>1.5 ng/ml for 35-49 yr, >2.0 ng/ml for 50-54 yr, and >3.0 ng/ml for 55-74 yr), or suspicious multiparametric MRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥3 lesion) were offered prostate biopsy. Outcome measurements and statistical analysis Endpoints were diagnosis of any and clinically significant prostate cancer, and alternative screening strategies were compared by a decision curve analysis. RESULTS AND LIMITATIONS: To date, 101 males have completed the first round of screening. The greatest proportion of participants are carriers of BRCA2 (n = 44), BRCA1 (n = 35), and ATM (n = 7) variants. Twenty-one have undergone biopsy, resulting in the detection of nine cases of cancer (seven clinically significant). For the detection of clinically significant prostate cancer, abnormal MRI (PI-RADS ≥3) demonstrated 100% sensitivity (7/7) with a negative predictive value (NPV) of 100%, whereas PSA-based screening alone had 57% (4/7) sensitivity with an NPV of 73%. Of six screening strategies evaluated in the decision curve analysis, MRI-based screening alone achieved superior net benefit at all threshold probabilities compared with PSA screening-detecting one additional cancer case per 7.5 patients, while avoiding more unnecessary biopsies at the same threshold probability. CONCLUSIONS: Disease prevalence is high among carriers of prostate cancer-associated pathogenic germline mutations. Early results suggest that MRI-based screening enhances early detection of clinically significant disease beyond PSA screening alone. PATIENT SUMMARY: In this study, we present the interim results from the PROGRESS prostate cancer screening trial. We found that in certain germline carriers of prostate cancer risk mutations, magnetic resonance imaging-based screening enhances detection of prostate cancer while reducing biopsies triggered, in comparison with traditional prostate-specific antigen screening strategies.

Margin convergence vs. superior capsular reconstruction for massive irreparable rotator cuff tears: outcomes are equivalent unless there is preoperative pseudoparesis.

BACKGROUND: Margin convergence (MC) and superior capsular reconstruction (SCR) are common treatment options for irreparable rotator cuff tears in younger patients, although they differ in associated costs and operative times. The purpose of this study was to compare range of motion, patient-reported outcomes (PROs), and reoperation rates following MC and SCR. We hypothesized superior outcomes after SCR relative to MC regarding functional outcomes, subjective measures, and reoperation rates. METHODS: This was a multicenter retrospective review of 59 patients from 3 surgeons treating irreparable rotator cuff tears with either MC (n = 28) or SCR (n = 31) and minimum 1-year follow-up from 2014-2019. Visual analog scale (VAS) for pain, Subjective Shoulder Value (SSV), active forward flexion (FF), external rotation (ER), retear rate, and conversion rate to reverse shoulder arthroplasty were evaluated. t tests and χ2 tests were used for continuous and categorical variables, respectively (P < .05). RESULTS: Baseline demographics, range of motion, and magnetic resonance imaging findings were similar between groups. Average follow-up was 31.5 months and 17.8 months for the MC and SCR groups, respectively (P < .001). The MC and SCR groups had similar postoperative FF (151° ± 26° vs. 142° ± 38°; P = .325) and ER (48° ± 12° vs. 46° ± 11°; P = .284), with both groups not improving significantly from their preoperative baselines. However, both cohorts demonstrated significant improvements in VAS score (MC: 7.3 to 2.5; SCR: 6.4 to 1.0) and SSV (MC: 54% to 82%; SCR: 38% to 87%). There were no significant differences in postoperative VAS scores, SSV, and rates of retear or rates of conversion to arthroplasty between the MC and SCR groups. In patients with preoperative pseudoparesis (FF < 90°), SCR (n = 9) resulted in greater postoperative FF than MC (n = 5) (141° ± 38° vs. 67° ± 24°; P = .002). CONCLUSION: Both MC and SCR demonstrated excellent postoperative outcomes in the setting of massive irreparable rotator cuff tear, with significant improvements in PROs and no significant differences in range of motion. Specifically for patients with preoperative pseudoparesis, SCR was more effective in restoring forward elevation. Further long-term studies are needed to compare outcomes and establish appropriate indications.

Impact of heart failure on COVID-19 patients: An insight from nationwide inpatient sample.

BACKGROUND: Patients with COVID-19 have been reported to experience adverse cardiovascular outcomes, such as myocarditis, acute myocardial infarction, and heart failure. Among these complications, heart failure (HF) has emerged as the most common critical complication during exacerbations of COVID-19, potentially leading to increased mortality rates and poorer clinical outcomes. We aimed to investigate the in-hospital outcomes of COVID-19 patients with HF. METHODS: We analyzed the Nationwide Inpatient Sample (NIS) dataset to select COVID-19 patients aged over 18 years who were hospitalized between January 1, 2020, and December 31, 2020, using ICD-10. Based on the presence of acute HF, the patients were divided into two cohorts. The clinical outcomes and complications were assessed at index admissions using STATA v.17." RESULTS: 1,666,960 COVID-19 patients were hospitalized in 2020, of which 156,755 (9.4%) had associated HF. COVID-19 patients with HF had a mean age of (72.38 ± 13.50) years compared to (62.3 ± 17.67) years for patients without HF. The HF patients had a higher prevalence of hypertension, hyperlipidemia, type 2 diabetes, smoking, and preexisting cardiovascular disease. Additionally, after adjusting for baseline demographics and comorbidities, COVID-19 patients with HF had higher rates of in-hospital mortality (23.86% vs. 17.63%, p<0.001), acute MI (18.83% vs. 10.91%, p<0.001), acute stroke (0.78% vs. 0.58%, p=0.004), cardiogenic shock (2.56% vs. 0.69%, p<0.001), and sudden cardiac arrest (5.54% vs. 3.41%, p<0.001) compared to those without HF. CONCLUSION: COVID-19 patients admitted with acute HF had worse clinical outcomes, such as higher mortality, myocardial infarction, cardiogenic shock, cardiac arrest, and a higher length of stay and healthcare than patients without HF.

Risk Factors Associated With Poor Outcomes After Quadriceps Tendon Repair.

Background: Ruptures of the quadriceps tendon present most frequently in older adults and individuals with underlying medical conditions. Purpose: To examine the relationship between patient-specific factors and tear characteristics with outcomes after quadriceps tendon repair. Study Design: Case-control study; Level of evidence, 3. Methods: A retrospective review was conducted on all patients who underwent quadriceps tendon repair between January 1, 2016, and January 1, 2021, at a single institution. Patients <18 years and those with chronic quadriceps tendon tears (>6 weeks to surgery) were excluded. Information was collected regarding patient characteristics, presenting symptoms, tear characteristics, physical examination findings, and postoperative outcomes. Poor outcome was defined as a need for revision surgery, complications, postoperative range of motion of (ROM) <110° of knee flexion, and extensor lag of >5°. Results: A total of 191 patients met the inclusion criteria. Patients were aged 58.5 ± 13.2 years at the time of surgery, were predominantly men (90.6%), and had a mean body mass index (BMI) of 32.2 ± 6.3 kg/m2. Patients underwent repair with either suture anchors (15.2%) or transosseous tunnels (84.8%). Postoperatively, 18.5% of patients experienced knee flexion ROM of <110°, 11.3% experienced extensor lag of >5°, 8.5% had complications, and 3.2% underwent revision. Increasing age (odds ratio [OR], 1.03 [95% CI, 1.004-1.07]) and female sex (OR, 3.82 [95% CI, 1.25-11.28]) were significantly associated with postoperative knee flexion of <110°, and increasing age (OR, 1.08 [95% CI, 1.04-1.14]) and greater BMI (OR, 1.14 [95% CI, 1.05-1.23]) were significantly associated with postoperative extensor lag of >5°. Current smoking status (OR, 15.44 [95% CI, 3.97-65.90]) and concomitant retinacular tears (OR, 9.62 (95% CI, 1.67-184.14]) were associated with postoperative complications, and increasing age (OR, 1.05 [95% CI, 1.02-1.08]) and greater BMI (OR, 1.08 [95% CI, 1.02-1.14]) were associated with risk of acquiring any poor outcome criteria. Conclusion: Patient-specific characteristics-such as increasing age, greater BMI, female sex, retinacular involvement, and current smoking status-were found to be risk factors for poor outcomes after quadriceps tendon repair. Further studies are needed to identify potentially modifiable risk factors that can be used to set patient expectations and improve outcomes.

Neoadjuvant PD-1 Inhibitors: A Tale of Two Cases.

Treatment responses for locally advanced cutaneous squamous cell carcinoma (cSCC) and Merkel cell carcinoma (MCC) are often short lived and are marred with recurrences. The introduction of adjuvant PD-1 inhibitors has demonstrated significant improvement in both, response rates, and duration of response. For patients with high-risk resectable disease, adjuvant treatments have not demonstrated an ability to reduce recurrence risk. However, there is an opportunity in the neoadjuvant setting to alter recurrence risk. Here we dem-onstrate two cases of neoadjuvant treatment of cSCC and MCC with impressive results.  J Drugs Dermatol. 2024;23(2):     doi:10.36849/JDD.7043e.

Phosphaturic mesenchymal tumor: management and outcomes of ten patients treated at a single institution.

BACKGROUND: Phosphaturic mesenchymal tumor (PMT) is a rare tumor that causes tumor-induced osteomalacia. Patients present with non-specific symptoms secondary to renal phosphate wasting and decreased bone mineralization. We sought to assess: (1) What are the common presenting features, laboratory and imaging findings, histologic findings of phosphaturic mesenchymal tumors? (2) What are the available treatment strategies for phosphaturic mesenchymal tumors and their long-term outcomes in terms of local recurrence and symptom control after treatment? METHODS: We retrospectively identified patients with a histologic diagnosis of PMT located in the axial or appendicular skeleton, or surrounding soft tissues. A total of 10 patients were finally included in our study. RESULTS: Median tumor size was 1.9 cm (range, 1.1 to 6.1) and median time from symptom onset to diagnosis was 3 years (range, 0.5 to 15 years). All patients but one presented with hypophosphatemia (median 1.9 mg/dL, range 1.2 to 3.2). Pre-operative FGF-23 was elevated in all cases (median 423.5 RU/mL, range 235 to 8950). Six patients underwent surgical resection, three were treated percutaneously (radiofrequency ablation or cryoablation), and one refused treatment. Only one patient developed local recurrence and no patients developed metastatic disease. At last follow-up, nine patients showed no evidence of disease and one was alive with disease. CONCLUSION: Phosphaturic mesenchymal tumor is a rare tumor presenting with non-specific symptoms. Surgery is the standard treatment when negative margins can be achieved without significant morbidity. In patients with small tumors in surgically-inaccessible areas, radiofrequency ablation or cryoablation can be performed successfully.

Assessment of Extent and Quality of Pharmacoeconomic Studies in India Using Quality of Health Economic Studies Score: A Targeted Literature Review.

OBJECTIVES: We assessed the quality of pharmacoeconomic studies conducted in India to report key areas of focus on the findings from the reviewed studies. METHODS: A targeted literature review was conducted using well-defined search strategy in PubMed to identify economic studies conducted in India from May 2017 to April 2022. Only economic evaluation studies were included, whereas trial-based cost analyses were excluded. The quality of included studies was assessed using the Quality of Health Economic Studies tool, which comprised 16 evaluation criteria related to objectives, source, funding, perspective, subgroup analysis, scales, and economic modeling related parameters. Based on scores (100 points), studies were rated as good (≥75), fair (50-74), and poor (≤49) quality. RESULTS: Search strategy provided 888 studies; 95 of these were economic studies, and 74 were included in the analysis. These 74 studies included budget impact analysis (n = 4), burden of illness (n = 8), cost-benefit analysis (n = 5), cost-consequences analysis (n = 1), cost-effectiveness analysis (n = 55), and cost-utility analysis (n = 1). The average quality score of studies was 64.08. Of the studies, 15 studies were rated as "good," 51 "fair," and 8 "poor." It was observed that primary outcome measures, stating negative outcomes, reporting bias, and implementing statistical and sensitivity analysis significantly affected the quality score. CONCLUSIONS: Most of the health economic studies conducted in India are of fair quality, and there is a need for standardization of guidelines and increase in number of Indian peer-reviewed health economics journals. A collaborative effort from pharma companies, policy makers, education experts, curriculum planners, and medical faculty is needed to promote quality economic studies.

Characterization of the intracellular neurexin interactome by in vivo proximity ligation suggests its involvement in presynaptic actin assembly.

Neurexins are highly spliced transmembrane cell adhesion molecules that bind an array of partners via their extracellular domains. However, much less is known about the signaling pathways downstream of neurexin's largely invariant intracellular domain (ICD). Caenorhabditis elegans contains a single neurexin gene that we have previously shown is required for presynaptic assembly and stabilization. To gain insight into the signaling pathways mediating neurexin's presynaptic functions, we employed a proximity ligation method, endogenously tagging neurexin's intracellular domain with the promiscuous biotin ligase TurboID, allowing us to isolate adjacent biotinylated proteins by streptavidin pull-down and mass spectrometry. We compared our experimental strain to a control strain in which neurexin, endogenously tagged with TurboID, was dispersed from presynaptic active zones by the deletion of its C-terminal PDZ-binding motif. Selection of this control strain, which differs from the experimental strain only in its synaptic localization, was critical to identifying interactions specifically occurring at synapses. Using this approach, we identified both known and novel intracellular interactors of neurexin, including active zone scaffolds, actin-binding proteins (including almost every member of the Arp2/3 complex), signaling molecules, and mediators of RNA trafficking, protein synthesis and degradation, among others. Characterization of mutants for candidate neurexin interactors revealed that they recapitulate aspects of the nrx-1(-) mutant phenotype, suggesting they may be involved in neurexin signaling. Finally, to investigate a possible role for neurexin in local actin assembly, we endogenously tagged its intracellular domain with actin depolymerizing and sequestering peptides (DeActs) and found that this led to defects in active zone assembly. Together, these results suggest neurexin's intracellular domain may be involved in presynaptic actin-assembly, and furthermore highlight a novel approach to achieving high specificity for in vivo proteomics experiments.

Using Total Corneal Astigmatism With Femtosecond Laser Cataract Surgery and Arcuate Keratotomy(ies) to Treat Low Amounts of Astigmatism.

PURPOSE: The aim of this study was to evaluate outcomes using total corneal astigmatism (TCA) to calculate arcuate keratotomy(ies) (AK) parameters performed with femtosecond laser-assisted cataract surgery to reduce low corneal astigmatism. METHODS: Patients who had femtosecond laser-assisted cataract surgery and AK with 0.50 diopter (D) to 1.30 D of TCA were included. Exclusion criteria were intraoperative complications, preexisting corneal surgery, and comorbidities that might adversely affect outcomes. Corneal tomography (Galilei G4, Zeimer Ophthalmic Systems AG) was performed preoperatively and 1 month postoperatively. TCA was input into the Donnenfeld limbal relaxing incisions nomogram to calculate the AK parameters. Preoperative and postoperative tomographic and subjective refractive measurements were compared. The Alpins method for vector analysis evaluated results. RESULTS: Eighty-two eyes of 82 patients were included. Mean preoperative TCA was significantly reduced from 0.80 ± 0.19 D to 0.51 D ± 0.26 D (P < 0.001). Preoperative posterior corneal astigmatism, -0.28 ± 0.13 D, was unchanged, postoperative posterior corneal astigmatism, -0.28 ± 0.14 D (P = 0.653). Target-induced astigmatism arithmetic mean (0.82 ± 0.21 D) was greater than that of the surgically induced astigmatism (0.70 ± 0.40 D), resulting in an arithmetic mean difference vector of 0.51 ± 0.27 D with a summated mean at 0.16 D at 20 degrees. The correction index was 0.87, indicating undercorrection. Angle of error arithmetic mean, -1.27 ± 23.27 degrees, indicated good alignment. CONCLUSIONS: Inputting TCA for calculation of femtosecond laser AK parameters can reduce low amounts of preoperative corneal astigmatism, thereby improving uncorrected vision.

Outcomes of an expedited same-day discharge protocol following cardiac implantable electronic device (CIED) implantation.

BACKGROUND: With increasing constraints on healthcare resources, greater attention is being focused on improved resource utilization. Prior studies have demonstrated safety of same-day discharge following CIED implantation but are limited by vague protocols with long observation periods. In this study, we evaluate the safety of an expedited 2 hour same-day discharge protocol following CIED implantation. METHODS: Patients undergoing CIED implantation at three centers between 2015 and 2021 were included. Procedural, demographic, and adverse event data were abstracted from the electronic health record. Patients were divided into same-day discharge (SDD) and delayed discharge (DD) cohorts. The primary outcome was complications including lead malfunction requiring revision, pneumothorax, hemothorax, lead dislodgement, lead perforation with tamponade, and mortality within 30 days of procedure. Outcomes were compared between the two cohorts using the χ2 test. RESULTS: A total of 4543 CIED implantation procedures were included with 1557 patients (34%) in the SDD cohort. SDD patients were comparatively younger, were more likely to be male, and had fewer comorbidities than DD patients. Among SDD patients, the mean time to post-operative chest X-ray was 2.6 h. SDD had lower rates of complications (1.3% vs 2.1%, p = 0.0487) and acute care utilization post-discharge (9.6% vs 14.0%, p < 0.0001). There was no difference in the 90-day infection rate between the cohorts. CONCLUSIONS: An expedited 2 hour same-day discharge protocol is safe and effective with low rates of complications, infection, and post-operative acute care utilization.

Cardiovascular Outcomes of Transcatheter Aortic Valve Implantation in Patients With Chronic Kidney Disease in Octogenarian Population.

Limited data are available regarding in-hospital outcomes of transcatheter aortic valve implantation (TAVI) in the octogenarian population with chronic kidney disease (CKD). We sought to study the cardiovascular outcomes of TAVI in CKD hospitalization with different stages at the national cohort registry. We used the National Inpatient Sample database to compare TAVI CKD low-grade (LG) (stage I to IIIa, b) versus TAVI CKD high-grade (HG) (stage IV to V) in octogenarians. Outcomes such as inpatient mortality, cardiogenic shock, new permanent pacemaker implantation, acute kidney injury), sudden cardiac arrest, mechanical circulatory support, major bleeding, transfusion, and resource utilization were compared between the 2 cohorts. A total of 74,766 octogenarian patients (TAVI CKD-HG n = 12,220; TAVI CKD-LG n = 62,545) were included in our study. On matched analysis, TAVI CKD-HG had higher odds of in-hospital mortality (adjusted odds ratio [aOR] 2.18, 95% confidence interval [CI] 1.0-2.5, p <0.0001), cardiogenic shock (aOR 1.22, 95% CI 1.07 to 1.39, p = 0.0019), permanent pacemaker implantation (aOR 1.14, 95% CI 1.06 to 1.23, p = 0.0006), acute kidney injury (aOR 1.19, 95% CI 1.13 to 1.27, p <0.0001), sudden cardiac arrest (aOR 1.32, 95% CI 1.09 to 1.61, p = 0.004), major bleeding (aOR 1.1, 95% CI 1.006 to 1.22, p <0.0368) and higher rates of blood transfusion (aOR 1.62, 95% CI 1.5 to 1.75, p <0.0001) when compared with the TAVI CKD-LG cohort. However, there was no statistically significant difference in the odds of cerebrovascular accident and mechanical circulatory support use between the 2 groups.

Trends and cardiovascular outcomes of Takotsubo syndrome with cardiogenic shock vs. mixed cardiogenic and septic shock: a nationwide propensity matched analysis.

INTRODUCTION: Takotsubo syndrome (TTS), also known as stress-induced cardiomyopathy, can be complicated by shock. The outcomes of patients with TTS complicated with cardiogenic shock (CS) versus mixed cardiogenic and septic shock (MS) is not known. METHODS: We queried Nationwide Inpatient Sample (NIS) from 2009-2020 to compare TTS patients with CS and MS using International Classification of Disease, Ninth & Tenth Edition, Clinical Modification (ICD- 9 & 10-CM) coding. In-hospital outcomes were compared using one: one propensity score matched (PSM) analysis. The primary outcome was in-hospital mortality. RESULTS: Of 23,126 patients with TTS 17,132 (74%) had CS, and 6,269 (26%) had MS. The mean age was 67 years in CS and 66 years in MS, and majority of patients were female (n = 17,775, 77%). On adjusted multivariate analysis, MS patients had higher odds of in-hospital mortality (aOR 1.44, 95% CI 1.36-1.52), AKI (aOR 1.53, 95% CI 1.48-1.58), pressor requirement (aOR 1.37, 95% CI 1.25-1.50). However, had lower odds of MCS use (aOR 0.44, 95% CI 0.40-0.48) and cardiac arrest (aOR: 0.81, 95% CI 0.73-0.90) (p-value <0.0001). Mean LOS and inflation-adjusted hospital charges were higher in MS. CONCLUSION: MS in the setting of TTS have higher rates of in-hospital mortality, AKI, and pressor requirements.

Analytical Validation of Aptamer-Based Serum Vancomycin Monitoring Relative to Automated Immunoassays.

The practice of monitoring therapeutic drug concentrations in patient biofluids can significantly improve clinical outcomes while simultaneously minimizing adverse side effects. A model example of this practice is vancomycin dosing in intensive care units. If dosed correctly, vancomycin can effectively treat methicillin-resistant streptococcus aureus (MRSA) infections. However, it can also induce nephrotoxicity or fail to kill the bacteria if dosed too high or too low, respectively. Although undeniably important to achieve effectiveness, therapeutic drug monitoring remains inconvenient in practice due primarily to the lengthy process of sample collection, transport to a centralized facility, and analysis using costly instrumentation. Adding to this workflow is the possibility of backlogs at centralized clinical laboratories, which is not uncommon and may result in additional delays between biofluid sampling and concentration measurement, which can negatively affect clinical outcomes. Here, we explore the possibility of using point-of-care electrochemical aptamer-based (E-AB) sensors to minimize the time delay between biofluid sampling and drug measurement. Specifically, we conducted a clinical agreement study comparing the measurement outcomes of E-AB sensors to the benchmark automated competitive immunoassays for vancomycin monitoring in serum. Our results demonstrate that E-ABs are selective for free vancomycin─the active form of the drug, over total vancomycin. In contrast, competitive immunoassays measure total vancomycin, including both protein-bound and free drug. Accounting for these differences in a pilot study consisting of 85 clinical samples, we demonstrate that the E-AB vancomycin measurement achieved a 95% positive correlation rate with the benchmark immunoassays. Therefore, we conclude that E-AB sensors could provide clinically useful stratification of patient samples at trough sampling to guide effective vancomycin dose recommendations.