The impact of baseline transmitral diastolic mean gradient on left atrial pressure reduction in patients undergoing transcatheter mitral valve edge-to-edge repair.

BACKGROUND: Elevated transmitral gradient post transcatheter mitral valve edge-to-edge repair (TEER) has been associated with worse outcomes. Whether an elevated baseline transmitral diastolic mean gradient (MG) ≥5 mmHg is associated with hemodynamic outcomes after TEER is unknown. METHODS: A total of 164 consecutive patients undergoing TEER at Mayo Clinic between June 2014 and May 2018 were analyzed in this retrospective study. Baseline demographics, as well as clinical, echocardiographic, and procedural data were obtained. Data on direct left atrial pressure (LAP) before and after TEER were recorded. Logistic regression models were constructed to evaluate the association between preprocedure transmitral diastolic mean gradient (pre-MG) and (1) improvement in LAP following TEER, (2) postprocedure transmitral diastolic mean gradient (post-MG). A decrease in LAP post TEER was considered an improvement in hemodynamic response. Pre-MG was categorized as: ≥5 and <5 mmHg. RESULTS: Median age of the cohort was 81.5 years (Q1: 76.3, Q3: 87) and 34% were female. At baseline, median transmitral diastolic MG was 4 mmHg (Q1: 3, Q3: 5) and median LAP was 19 mmHg (Q1:16, Q3: 23.5). In a multivariable model, adjusted for age and sex, patients with pre-MG ≥ 5 mmHg were less likely to see an improvement in LAP post TEER (adjusted odds ratio [aOR]: 0.22, 95% confidence interval [CI]: 0.09, 0.55; p = 0.001) and more likely to have elevated post-MG (aOR; 7.08, 95% CI: 2.93, 17.13; p < 0.001). CONCLUSION: Higher pre-MG (≥5 mmHg) was associated with a lower reduction in LAP and higher residual transmitral gradient following TEER suggesting other potential contributors to increased LAP besides mitral regurgitation as a cause of elevated baseline MG.

Pigmented Lesions of the Nail Unit.

Pigmented lesions of the nail unit are commonly encountered in the clinical setting. Yet, they often present a unique challenge to clinicians because of a broad differential diagnosis or unfamiliarity with clinical and histopathologic features. A wide variety of causes exist ranging from benign lesions such as subungual hemorrhage to malignant lesions such as subungual melanoma. Identifying the underlying cause is key to appropriate management and follow-up in these patients. Although emerging clinical tools such as dermoscopy can be very useful in evaluation of these lesions, histopathologic analysis remains the gold standard. In this review, we discuss and provide a summary of important clinical and histopathological concepts of pigmented lesions of the nail unit with special focus on longitudinal melanonychia, melanotic macule, melanocytic nevus, subungual melanoma, along with discussion of some nonmelanocytic lesions.

Exercise Cardiac Catheterization for Hemodynamic Evaluation of Paradoxical Low-Flow Low-Gradient Severe Aortic Stenosis.

Patients with paradoxical low-flow low-gradient aortic stenosis pose a diagnostic challenge when it comes to assessing the severity of aortic stenosis (AS) noninvasively. We describe 2 patients who underwent exercise cardiac catheterization to augment their cardiac output and assess the severity of AS invasively to allow differentiation of true severe AS from pseudo-severe AS.

Right Atrial Mass Biopsy Using Endobronchial Forceps.

A 72-year-old male with past medical history of complete heart block status post pacemaker in 2019, renal cell carcinoma, and thyroid cancer presented with a 4-cm right atrial mass incidentally found on routine transthoracic echocardiography. Cardiovascular computed tomography angiogram revealed an infiltrative mildly enhancing soft-tissue density along the right and left atrioventricular grooves, anterior interventricular groove, interatrial septum, free wall of the right ventricle, and right atria. Transesophageal echocardiography at the time of the cardiac biopsy revealed a heterogeneous mass extending along the interatrial septum into the superior vena cava, which appeared partially occluded, as well as probable involvement of the aortic root. After several attempts with traditionally used devices, an endobronchial alligator forceps was used to biopsy the right atrial mass under intracardiac echocardiographic guidance, with no complications.

A Systematic Review and Meta-analysis of Opioids vs Nonopioids in Acute Pancreatitis.

Background and Aims: Although abdominal pain is one of the major criteria to diagnose acute pancreatitis (AP), there are no standardized guidelines to treat this troublesome symptom in the hospital setting. The aims of the study are to conduct a meta-analysis and to assess the efficacy of nonopioids vs opioids for pain management in AP. Methods: We searched the medical literature through May 2021 to identify randomized controlled trials that examined the efficacy of opioids with nonopioids in AP pain management. Efficacy was reported as odds ratio (OR) with 95% confidence intervals (CIs) of each comparison tested. Results: We identified 7 eligible randomized controlled trials, containing 389 patients. No significant difference in terms of pain intensity at day 1 (OR 0.82, 95% CI -2.55 to 4.19) was found between opioids and nonopioids. Nonopioids have a significantly high risk of supplementary analgesic use compared with opioids (OR 3.87, 95% CI 1.25-12.04). However, this significance is not seen when comparing nonsteroidal anti-inflammatory drugs and paracetamol with opioids (OR 1.67, 95% CI 0.73-3.82) after excluding trials with procaine. Opioids did not show a significant increase in the complications of pancreatitis, nausea and vomiting, sedation, and deaths when compared with nonopioids. Conclusion: We found nonopioids, especially nonsteroidal anti-inflammatory drugs and paracetamol, can provide adequate pain relief in patients with AP with no change in supplementary analgesic use and adverse events when compared with opioids. Further research is needed to optimize the use of nonopioids along or in combination with opioids for better pain control in patients with AP.

Outcomes of Radial Versus Femoral Access in Patients With Severe Aortic Stenosis Undergoing Percutaneous Coronary Intervention Prior to Transcatheter Aortic Valve Replacement.

BACKGROUND: The safety and feasibility of radial access in patients undergoing percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) has not been studied. METHODS: This study included consecutive patients who underwent PCI within 30 days before TAVR at Mayo Clinic. Vascular access was left to the discretion of the operator. Baseline demographics, procedural data, PCI outcomes, and subsequent transfemoral TAVR outcomes were extracted from patient charts. RESULTS: A total of 331 patients were included in this study, with 107 patients undergoing PCI via radial access (rPCI), and 224 via femoral access (fPCI). Mean age was 80.6 years and 35.6% were females (35.5% rPCI vs 35.3% fPCI). More patients in the fPCI group had previous coronary artery bypass graft surgery (13.1% rPCI vs 34.4% fPCI; P<.001). Fluoroscopy time (13.36 minutes vs 18.86 minutes; P<.001) and contrast use (115 mL vs 140 mL; P<.01) were lower in the rPCI group than in the fPCI group. Crossover rate from radial to femoral was 6.5%. There were more access-site hematomas in the fPCI group (2.8% rPCI vs 14.3% fPCI; P<.001), with no statistically significant rate of other access-related complications. There was no difference in stroke, myocardial infarction, cardiac arrest, or unplanned surgery. There was no difference in bleeding or stroke between both groups during subsequent transfemoral TAVR. CONCLUSION: Radial access for pre-TAVR PCI is feasible and safe and is associated with a lower rate of access-site hematoma. This study supports the increased use of transradial access for pre-TAVR PCI.

Systematic review and network meta-analysis: efficacy of licensed drugs for abdominal bloating in irritable bowel syndrome with constipation.

BACKGROUND: Although bloating is a highly prevalent and troublesome symptom in irritable bowel syndrome with constipation (IBS-C), treatment is empirical with no specific guidelines for its management. AIM: To conduct a pairwise and network meta-analysis, using a frequentist approach, of Food and Drug Administration-licensed drugs for IBS-C comparing their efficacy for abdominal bloating as a specific endpoint. METHODS: We searched the medical literature through December 2020 to identify randomised controlled trials (RCTs) in IBS-C, with abdominal bloating reported as a dichotomous assessment. Efficacy of each drug was reported as a pooled relative risk (RR) with 95% confidence intervals (CIs) to summarise effect of each comparison tested. Treatments were ranked according to their P-score. RESULTS: We identified 13 eligible RCTs, containing 10 091 patients. Linaclotide 290 µg o.d., lubiprostone 8 µg b.d., tenapanor 50 mg b.d. and tegaserod 6 mg b.d. were all superior to placebo for abdominal bloating in patients with IBS-C, in both pairwise and the network meta-analyses. Linaclotide demonstrated the greatest improvement in abdominal bloating in both pairwise and network meta-analysis (RR of failure to achieve an improvement in abdominal bloating = 0.78; 95% CI 0.74-0.83, number needed to treat = 7, P-score 0.97). Indirect comparison revealed no significant differences between individual drugs. CONCLUSIONS: We found all licensed drugs for IBS-C to be superior to placebo for abdominal bloating. Linaclotide appeared to be the most efficacious at relieving abdominal bloating. Further research is needed to assess long-term efficacy of these agents and to better understand the precise mechanism of improving bloating.

Diabetes Mellitus as a Risk Factor for Acute Postoperative Complications Following Elective Adult Spinal Deformity Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Diabetes mellitus is a highly prevalent disease in the United States. Adult spinal deformity (ASD) surgery encompasses a wide variety of spinal disorders and is associated with a morbidity rate between 20% and 80%. Considering utilization of spinal surgery will continue to increase, this study investigates the influence of diabetes mellitus on acute postoperative outcomes following elective ASD surgery. METHODS: The 2010-2014 American College of Surgeon's National Surgical Quality Improvement Program database was queried using Current Procedural Terminology and International Classification of Diseases (9th Revision) diagnosis codes relevant to ASD surgery. Patients were divided into cohorts based on their diabetic status. Bivariate and multivariate logistic regression analyses were employed to identify which 30-day postoperative outcomes patients are at risk for. RESULTS: A total of 5809 patients met the inclusion criteria for the study of which 4553 (84.2%) patients were nondiabetic, 578 (10.7%) patients had non-insulin-dependent diabetes mellitus (NIDDM), and 275 (5.1%) patients had insulin-dependent diabetes mellitus (IDDM). Diabetes status was significantly associated with length of stay ≥5 days (NIDDM: odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.02-1.58, P = .034; IDDM: OR = 1.55, 95% CI = 1.15-2.09, P = .004), any complication (NIDDM: OR = 1.26, 95% CI = 1.01-1.58, P = .037), urinary tract infection (NIDDM: OR = 1.87, 95% CI = 1.14-3.05, P = .012), and cardiac complications (IDDM: OR = 4.05, 95% CI = 1.72-9.51, P = .001). CONCLUSIONS: Given the prevalence of diabetes, surgeons will invariably encounter these patients for ASD surgery. The present study identifies the increased risk NIDDM and IDDM patients experience following ASD surgery. Quantification of this increased risk may improve the selection of appropriate surgical candidates, patient risk stratification, and patient postoperative safety.

Predictors for Non-Home Patient Discharge Following Elective Adult Spinal Deformity Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Adult spinal deformity (ASD) surgery encompasses a wide variety of spinal disorders and is associated with a morbidity rate between 20% and 80%. The utilization of spinal surgery has increased and this trend is expected to continue. To effectively deal with an increasing patient volume, identifying variables associated with patient discharge destination can expedite placement and reduce length of stay. METHODS: The 2013-2014 American College of Surgeons National Surgical Quality Improvement Program database was queried using Current Procedural Terminology and International Classification of Diseases, Ninth Revision diagnosis codes relevant to ASD. Patients were divided based on discharge destination. Bivariate and multivariate logistic regression analyses were employed to identify predictors for patient discharge destination and hospital length of stay. RESULTS: A total of 4552 patients met inclusion criteria, of which 1102 (24.2%) had non-home discharge. Multivariate regression revealed total relative value unit (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 1.00-1.01); female sex (OR = 1.54, 95% CI = 1.32-1.81); American Indian, Alaska Native, Asian, Native Hawaiian, or Pacific Islander versus black race (OR = 0.52, 95% CI = 0.35-0.78, P = .002); age ≥65 years (OR = 3.72, 95% CI = 3.19-4.35); obesity (OR = 1.18, 95% CI = 1.01-1.38, P = .034); partially/totally functionally dependent (OR = 2.11, 95% CI = 1.49-2.99); osteotomy (OR = 1.42, 95% CI = 1.12-1.80, P = .004) pelvis fixation (OR = 2.38, 95% CI = 1.82-3.11); operation time ≥4 hours (OR = 1.74, 95% CI = 1.47-2.05); recent weight loss (OR = 7.66, 95% CI = 1.52-38.65; P = .014); and American Society of Anesthesiologists class ≥3 (OR = 1.80, 95% CI = 1.53-2.11) as predictors of non-home discharge. P values were <.001 unless otherwise noted. Additionally, multivariate regression found non-home discharge to be a significant variable in prolonged length of stay. CONCLUSIONS: The authors suggest these results can be used to inform patients preoperatively of expected discharge destination, anticipate patient discharge needs postoperatively, and reduce health care costs and morbidity associated with prolonged LOS.

Predictors for Patient Discharge Destination After Elective Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective study of prospectively collected data. OBJECTIVE: To identify risk factors for nonhome patient discharge after elective anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: ACDF is one of the most performed spinal procedures and this is expected to increase in the coming years. To effectively deal with an increasing patient volume, identifying variables associated with patient discharge destination can expedite placement applications and subsequently reduce hospital length of stay. METHODS: The 2011 to 2014 ACS-NSQIP database was queried using Current Procedural Terminology (CPT) codes 22551 or 22554. Patients were divided into two cohorts based on discharge destination. Bivariate and multivariate logistic regression analyses were employed to identify predictors for patient discharge destination and extended hospital length of stay. RESULTS: A total of 14,602 patients met the inclusion criteria for the study of which 498 (3.4%) had nonhome discharge. Multivariate logistic regression found that Hispanic versus Black race/ethnicity (odds ratio, OR =0.21, 0.05-0.91, P =0.037), American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander versus Black race/ethnicity (OR = 0.52, 0.34-0.80, p-value = 0.003), White versus Black race/ethnicity (OR = 0.55, 0.42-0.71), elderly age ≥65 years (OR = 3.32, 2.72-4.06), obesity (OR = 0.77, 0.63-0.93, P = 0.008), diabetes (OR = 1.32, 1.06-1.65, P = 0.013), independent versus partially/totally dependent functional status (OR = 0.11, 0.08-0.15), operation time ≥4 hours (OR = 2.46, 1.87-3.25), cardiac comorbidity (OR = 1.38, 1.10-1.72, P = 0.005), and ASA Class ≥3 (OR = 2.57, 2.05-3.20) were predictive factors in patient discharge to a facility other than home. In addition, multivariate logistic regression analysis also found nonhome discharge to be the most predictive variable in prolonged hospital length of stay. CONCLUSION: Several predictive factors were identified in patient discharge to a facility other than home, many being preoperative variables. Identification of these factors can expedite patient discharge applications and potentially can reduce hospital stay, thereby reducing the risk of hospital acquired conditions and minimizing health care costs. LEVEL OF EVIDENCE: 3.

Removal of Abnormal Myofilament O-GlcNAcylation Restores Ca2+ Sensitivity in Diabetic Cardiac Muscle.

Contractile dysfunction and increased deposition of O-linked ß-N-acetyl-d-glucosamine (O-GlcNAc) in cardiac proteins are a hallmark of the diabetic heart. However, whether and how this posttranslational alteration contributes to lower cardiac function remains unclear. Using a refined ß-elimination/Michael addition with tandem mass tags (TMT)-labeling proteomic technique, we show that CpOGA, a bacterial analog of O-GlcNAcase (OGA) that cleaves O-GlcNAc in vivo, removes site-specific O-GlcNAcylation from myofilaments, restoring Ca(2+) sensitivity in streptozotocin (STZ) diabetic cardiac muscles. We report that in control rat hearts, O-GlcNAc and O-GlcNAc transferase (OGT) are mainly localized at the Z-line, whereas OGA is at the A-band. Conversely, in diabetic hearts O-GlcNAc levels are increased and OGT and OGA delocalized. Consistent changes were found in human diabetic hearts. STZ diabetic hearts display increased physical interactions of OGA with α-actin, tropomyosin, and myosin light chain 1, along with reduced OGT and increased OGA activities. Our study is the first to reveal that specific removal of O-GlcNAcylation restores myofilament response to Ca(2+) in diabetic hearts and that altered O-GlcNAcylation is due to the subcellular redistribution of OGT and OGA rather than to changes in their overall activities. Thus, preventing sarcomeric OGT and OGA displacement represents a new possible strategy for treating diabetic cardiomyopathy.

Cardiac troponin I Pro82Ser variant induces diastolic dysfunction, blunts ß-adrenergic response, and impairs myofilament cooperativity.

Troponin I (TnI) variant Pro82Ser (cTnIP82S) was initially considered a disease-causing mutation; however, later studies suggested the contrary. We tested the hypothesis of whether a causal link exists between cTnIP82S and cardiac structural and functional remodeling, such as during aging or chronic pressure overload. A cardiac-specific transgenic (Tg) mouse model of cTnIP82S was created to test this hypothesis. During aging, Tg cTnIP82S displayed diastolic dysfunction, characterized by longer isovolumetric relaxation time, and impaired ejection and relaxation time. In young, Tg mice in vivo pressure-volume loops and intact trabecular preparations revealed normal cardiac contractility at baseline. However, upon ß-adrenergic stimulation, a blunted contractile reserve and no hastening in left ventricle relaxation were evident in vivo, whereas, in isolated muscles, Ca(2+) transient amplitude isoproterenol dose-response was blunted. In addition, when exposed to chronic pressure overload, Tg mice show exacerbated hypertrophy and decreased contractility compared with age-matched non-Tg littermates. At the molecular level, this mutation significantly impairs myofilament cooperative activation. Importantly, this occurs in the absence of alterations in TnI or myosin-binding protein C phosphorylation. The cTnIP82S variant occurs near a region of interactions with troponin T; therefore, structural changes in this region could explain its meaningful effects on myofilament cooperativity. Our data indicate that cTnIP82S mutation modifies age-dependent diastolic dysfunction and impairs overall contractility after ß-adrenergic stimulation or chronic pressure overload. Thus cTnIP82S variant should be regarded as a disease-modifying factor for dysfunction and adverse remodeling with aging and chronic pressure overload.