Multidisciplinary Management of Opioid Use-Related Infective Endocarditis: Treatment, QTc Values, and Cardiac Arrests due to Ventricular Fibrillation.

(1) Background: The opioid epidemic has led to an increase in cardiac surgery for infective endocarditis (IE-CS) related to injection use of opioids (OUD) and other substances and a call for a coordinated approach to initiate substance use disorder treatment, including medication for OUD (MOUD), during IE-CS hospitalizations. We sought to determine the effects of the initiation of a multi-disciplinary endocarditis evaluation team (MEET) on MOUD use, electrocardiographic QTc measurements and cardiac arrests due to ventricular fibrillation (VF) in patients with OUD. (2) Methods and Results: A historical group undergoing IE-CS at Yale-New Haven Hospital prior to MEET initiation, Group I (43 episodes of IE-CS, 38 patients) was compared to 24 patients undergoing IE-CS after MEET involvement (Group II). Compared to Group l, Group II patients were more likely to receive MOUD (41.9 vs. 95.8%, p < 0.0001), predominantly methadone (41.9 vs. 79.2%, p = 0.0035) at discharge. Both groups had similar QTcs: approximately 30% of reviewed electrocardiograms had QTcs ≥ 470 ms and 17%, QTcs ≥ 500 ms. Cardiac arrests due to VF were not uncommon: Group I: 9.3% vs. Group II: 8.3%, p = 0.8914. Half occurred in the 1-2 months after surgery and were contributed to by pacemaker malfunction/ management and half were related to opioid use. (3) Conclusions: MEET was associated with increased MOUD (predominantly methadone) use during IE-CS hospitalizations without an increase in QTc prolongation or cardiac arrest due to VF compared to Group I, but events occurred in both groups. These arrests were associated with pacemaker issues or a return to opioid use. Robust follow-up of IE-CS patients is essential, as is further research to clarify the longer-term effects of MEET on outcomes.

Abernethy malformation: A comprehensive review.

Abernethy malformation is a rare condition in which portomesenteric blood bypasses the liver and drains into the systemic vein through a partial or complete shunt. It is categorised into two types on the basis of the shunt pattern between the portal vein and systemic vein. Abernethy malformation is associated with multiple congenital anomalies and acquired complications. A detailed understanding of anatomy and embryology is a prerequisite to interpret the imaging findings. Computed tomography and magnetic resonance angiography can delineate the shunt anatomy and evaluate the concomitant malformations. It is essential to differentiate Abernethy malformation from intrahepatic portosystemic shunts and acquired extrahepatic portosystemic shunts. Mild metabolic abnormalities are treated with dietary modifications and medical therapy. Definitive treatment is done in symptomatic patients. Generally, type I Abernethy patients undergo liver transplantation, and type II undergo shunt occlusion by surgery or transcatheter coiling.

Isolated right subclavian artery with interrupted aortic arch, ventricular septal defect and bilateral patent ductus arteriosus: a rare congenital anomaly.

Isolation of the left subclavian artery or its anomalous origin from the pulmonary artery has been documented in several cases, especially in association with a right-sided aortic arch. However, similar anomaly involving the right subclavian artery has been less frequently reported. Isolated right subclavian artery in association with interrupted aortic arch (IAA) is extremely rare, and only three cases have been reported so far. Here, we have presented yet another case of isolated right subclavian artery associated with ventricular septal defect, type B IAA and bilateral patent ductus arteriosus.

Symptomatic Presentation of Acute Myocardial Infarction in Heart Transplantation Patients.

Patients with acute myocardial infarction with a history of an orthotopic heart transplantation rarely present with classic anginal symptoms, secondary to cardiac denervation. We present 2 cases, the first of a patient with a ST-segment elevation myocardial infarction and the second who presented with a non-ST-segment elevation myocardial infarction. Both patients presented with typical symptoms and were treated with percutaneous coronary intervention. (Level of Difficulty: Intermediate.).

Fecal Scrotal Abscess Secondary to Spontaneous Retroperitoneal Perforation of Ascending Colon.

INTRODUCTION: Fecal abscess or enterocutaneous fistulas of the scrotum are rare and are invariably the result of incarcerated bowel loop in inguinal hernia. Spontaneous perforation of the colon (SPC) having no definite cause is also rare. Much rarer is posterior colonic perforations causing an extensively large retroperitoneal abscess. Similarly, spread of retroperitoneal abscess to the thigh or scrotum has rarely been reported. We report a case of spontaneous posterior perforation of ascending colon resulting in large retroperitoneal abscess eventually causing scrotal abscess, which resolved on conservative treatment and drainage of the scrotal fecal abscess. Case Presentation. A 20-year-old male presented with gradually increasing noncolicky pain right side abdomen with nonprojectile vomiting, obstipation, and progressive abdominal distension. Clinically, the abdomen was tender with guarding over the right side with signs of inflammation on the right side back with no associated hernia. On conservative treatment, he was gradually improved but developed right side scrotal abscess a week later. CT abdomen showed a large retroperitoneal collection having multiple internal air lucencies, displacing ascending colon and caecum medically with discontinuity in the posterior wall of ascending colon. The large retroperitoneal collection was extending from right pararenal and posterior perihepatic soft tissue planes to the right iliac fossa and thigh. On drainage of the scrotal abscess, about 350 ml of fecal contents was evacuated. The patient gradually recovered and was discharged on conservative treatment with an uneventful 4-year follow-up. CONCLUSION: Diagnosis of retroperitoneal perforation of the colon is often delayed due to the absence of peritoneal irritation. An extensively large retroperitoneal abscess may spread the infection to the scrotum and thigh due to extreme pressure, possibly by dissecting away the transversalis fascia through a deep ring along the side of the spermatic cord. Timely performed CT/MRI can avoid delay in the diagnosis of retroperitoneal abscess and further spread of infection.

Worldwide Survey of COVID-19-Associated Arrhythmias.

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Determinants of regeneration and strength of hamstrings after anterior cruciate ligament reconstruction-fate of hamstring tendon.

BACKGROUND AND AIM: Arthroscopic reconstruction of anterior cruciate ligament (ACL) surgical procedure using hamstring autograft is the most common surgery performed in the arena of sports medicine and arthroscopy. Most studies in literature are ambiguous regarding the fate of hamstrings based on function, regenerative potential, and cross-sectional area (CSA). The aim of this research study is analysis of the fate of hamstring tendons (both semitendinosus and gracilis) during the time course for determinants of regeneration and strength. METHODS: Fifty patients who were operated for unilateral isolated ACL reconstruction from July 2015 to June 2018 were evaluated for the fate of harvested hamstring tendons which included the following: regeneration, cross-sectional area (CSA), strength, and insertion of regenerated hamstrings by isometric torque and isokinetic strength. MRI of knee was performed for both knees concerning the semitendinosus (ST), gracilis (G), Sartorius, biceps femoris, and medial head of gastrocnemius. RESULTS: Eighty-four percent men and 16% women within a mean patient age of 34 ± 4.12 years were evaluated and all 50 (100%) patients demonstrated hamstring regeneration by the MRI measurements at six months and at one year post-ACL reconstruction. The torque of isometric knee flexion measured in 60° was found to be remarkably lower in the ACL-reconstructed lower extremity compared to that of the contralateral limb (87.13 ± 20.18% of BW), at 90° (49.17 ± 15.09% BW), and at 105° (43.91 ± 13.17% BW), respectively (p < 0.01). However, at 30° flexion and 45° flexion, the difference was insignificant (116.48 ± 21.07% BW for 30° and 100.16 ± 25.12% BW for 45°). CONCLUSIONS: It was found that the properties of musculotendinous units of ST and G were significantly transformed after their harvesting for ACL reconstruction and these weaknesses contribute to the flexion deficit of knee in the deeper range of flexion in the operated limb. Therefore, approaches facilitating tendon regeneration and preservation must be warranted.

The Impact of the COVID-19 Pandemic on Cardiac Electrophysiology Training: A Survey Study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a significant decrease in volume of electrophysiology (EP) procedures. There has been concern that trainees may not achieve the procedural numbers required to graduate as independent electrophysiologists within the usual timeline. We sought to determine the impact of the COVID-19 pandemic on the percentage of clinical cardiac EP (CCEP) fellows in jeopardy of not meeting procedural volume requirements and overall sentiments regarding preparedness of fellows for independent practice. METHODS: We surveyed CCEP fellows and program directors about baseline procedural volumes, curriculum changes due to the pandemic, and attitudes about preparedness for board examinations and independent practice. RESULTS: Ninety-nine fellows and 27 program directors responded to the survey. Ninety-eight percent of responding fellows reported a decrease in procedural volume as a result of the pandemic. Program directors reported an overall decrease in annual number of ablations and device procedures performed by each fellow during the 2019-2020 academic year compared to the preceding year. Despite this, a minority of fellows and program directors reported concerns about meeting Accreditation Council for Graduate Medical Education procedural requirements for devices (9% and 4%, respectively) and ablation (19% and 9%) or preparedness for independent practice after a 2-year fellowship. CONCLUSIONS: The COVID-19 pandemic has resulted in a decrease in procedural volume for CCEP trainees, but the majority of fellows and program directors do not anticipate major barriers to timely graduation. This may change with COVID-19 resurgence and further interruptions in training.

Impact of medial open-wedge high tibial osteotomy for medial compartment osteoarthritis of the knee.

BACKGROUND: Most populations worldwide, who are used to squatting and sitting cross-legged for their activities of daily living, largely comprise the lower socioeconomic strata, thus making them candidates for exclusion for total knee arthroplasty. Proximal/high tibial osteotomy (HTO) is a preferred strategy for clinically symptomatic osteoarthritis (OA) with genu varum due to painful medial compartment OA which is not amenable to conservative measures. AIM: To evaluate the outcomes of medial open-wedge HTO along with autologous bone grafting and buttress plate for the treatment of genu varum due to OA of the knee in a rural population of central India. METHODS: A total of 65 knees in 56 patients with a mean age of 58.22 ± 5.63 years with genu varum due to intractable painful knee OA were treated with medial open-wedge HTO along with autologous bone grafting and buttress plate osteosynthesis from June 2015 to May 2018. The mean preoperative radiological angle of genu varum was 13.4°. Clinical outcomes were assessed by the range of movement, knee scores, pain scores, and functional scores. Radiographic studies were performed preoperatively and at regular intervals during the follow-up period. RESULTS: All patients reported pain relief immediately after the osteotomy and during the long-term analysis covering between one to three years. The genu varum angle was overcorrected to approximately four degrees in all patients. There was a loss of reduction by approximately three degrees in all patients at around six weeks postoperatively. Preoperative knee movements were restored in all patients. No major perioperative complications were noted during surgery and postoperative follow-up and the clinical scores were significantly improved during the final analysis which revealed good pain relief. CONCLUSION: Medial open-wedge HTO is a reliable, safe, practical, physiological, and feasible treatment for populations who are used to increased activity in their occupation and lifestyle and is associated with excellent short-term and long-term results for OA in genu varum knees.

Risk of COVID-19 infection after cardiac electrophysiology procedures.

BACKGROUND: During the COVID-19 pandemic, attempts to conserve resources and limit virus spread have resulted in delay of nonemergent procedures across all medical specialties, including cardiac electrophysiology (EP). Many patients have delayed care and continue to express concerns about potential nosocomial spread of coronavirus. OBJECTIVE: To quantify risk of development of COVID-19 owing to in-hospital transmission related to an EP procedure, in the setting of preventive measures instituted in our laboratory areas. METHODS: We contacted patients by telephone who underwent emergent procedures in the electrophysiology lab during the COVID-19 surge at our hospital (March 16, 2020, to May 15, 2020, reaching daily census 450 COVID-19 patients,) ≥2 weeks after the procedure, to assess for symptoms of and/or testing for COVID-19, and assessed outcomes from medical record review. RESULTS: Of the 124 patients undergoing EP procedures in this period, none had developed documented or suspected coronavirus infection. Seven patients described symptoms of chest pain, dyspnea, or fever; 3 were tested for coronavirus and found to be negative. Of the remaining 4, 2 had a more plausible alternative explanation for the symptoms, and 2 had transient symptoms not meeting published criteria for probable COVID-19 infection. CONCLUSION: Despite a high hospital census of COVID-19 patients during the period of hospital stay for an EP procedure, there were no likely COVID-19 infections occurring in follow-up of at least 2 weeks. With proper use of preventive measures as recommended by published guidelines, the risk of nosocomial spread of COVID-19 to patients in the EP lab is low.

Single Ascending Dose Study to Assess Pharmacokinetic Linearity, Safety, and Tolerability of Trimetazidine - Modified Release in Healthy Human Subjects.

AIM: This study assessed the linearity of pharmacokinetics (PK) of trimetazidine (TMZ) modified-release tablets (indicated in adults as an add-on therapy for stable angina pectoris) and measured its renal elimination, safety, and tolerability in healthy subjects. METHODS: This was a randomized, open-label, single-ascending dose study in healthy subjects. Subjects were administered with a single dose of 35, 70, or 105 mg TMZ-modified release tablets (six subjects each). Pharmacokinetic evaluations and safety analysis were performed before the first dose and till 48 h post-first dose. RESULTS: Following administration of 35, 70, and 105 mg TMZ-modified release; the Cmax (mean±SD) was 79.32 (±23.08), 153.17 (±23.08), and 199.67 (±23.08) ng/mL, the Tmax was 5.42 (±0.49), 4.51 (±1.27), and 4.57 (±0.96) h, t1/2 was 7.75 (±1.62), 6.40 (±1.23), and 6.50 (±1.18) h, AUC(0-inf) was 1116.89 (±378.35), 1838.39 (±284.50), and 2504.84 (±348.35) ng.h/mL, CLR was 13.70 (±2.24), 14.80 (±5.91), and 19.58 (±6.24) L·h-1 and CL/F was 33.69 (±8.51), 38.85 (±6.15), and 42.74 (±7.10) L·h-1, respectively. Slope estimates for AUC(0-inf), AUC(0-t), and Cmax were less than 1. Corresponding 95% CI of the slope for the AUC parameters excluded 1, indicating that the deviation from dose-proportionality was statistically significant. Corresponding 95% CI of the slope for Cmax included 1, indicating that the less than dose-proportional increase in Cmax was not statistically significant. No significant adverse events were observed. CONCLUSION: Substantial deviation from a dose-proportional increase in AUC(0-inf) and AUC(0-t) suggested a non-linear PK for TMZ-modified release. Single dose of TMZ-modified release was well tolerated and safe.

Enhanced electrocardiographic monitoring of patients with Coronavirus Disease 2019.

Background: Many of the drugs being used in the treatment of the ongoing pandemic coronavirus disease 2019 (COVID-19) are associated with QT prolongation. Expert guidance supports electrocardiographic (ECG) monitoring to optimize patient safety. Objective: The purpose of this study was to establish an enhanced process for ECG monitoring of patients being treated for COVID-19. Methods: We created a Situation Background Assessment Recommendation tool identifying the indication for ECGs in patients with COVID-19 and tagged these ECGs to ensure prompt over reading and identification of those with QT prolongation (corrected QT interval > 470 ms for QRS duration ≤ 120 ms; corrected QT interval > 500 ms for QRS duration > 120 ms). This triggered a phone call from the electrophysiology service to the primary team to provide management guidance and a formal consultation if requested. Results: During a 2-week period, we reviewed 2006 ECGs, corresponding to 524 unique patients, of whom 103 (19.7%) met the Situation Background Assessment Recommendation tool-defined criteria for QT prolongation. Compared with those without QT prolongation, these patients were more often in the intensive care unit (60 [58.3%] vs 149 [35.4%]) and more likely to be intubated (32 [31.1%] vs 76 [18.1%]). Fifty patients with QT prolongation (48.5%) had electrolyte abnormalities, 98 (95.1%) were on COVID-19-related QT-prolonging medications, and 62 (60.2%) were on 1-4 additional non-COVID-19-related QT-prolonging drugs. Electrophysiology recommendations were given to limit modifiable risk factors. No patient developed torsades de pointes. Conclusion: This process functioned efficiently, identified a high percentage of patients with QT prolongation, and led to relevant interventions. Arrhythmias were rare. No patient developed torsades de pointes.

Effect of age and renal impairment on the pharmacokinetics and safety of trimetazidine: An open-label multiple-dose study.

This study evaluated the effect of age and renal impairment on pharmacokinetics of trimetazidine (TMZ) in healthy elderly and renally impaired subjects and assess safety and tolerability. In this open-label, multi-dose study, 73 subjects were divided into six treatment groups: (1) 55-65 years; (2) 66-75 years; (3) >75 years (dosing for groups 1-3 [healthy]: B.D. for 4 days), (4) mild renally impaired (dosed B.D. for 8 days); (5) moderate renally impaired (dosed O.D. for 8 days); and (6) severe renally impaired-no dialysis (dosed once every 48 h for 8 days). Blood and urine samples were collected and analyzed. The geometric least squares mean ratios for; Group 2 and 1 of AUC(0-τ)ss was 112.2 (90% CI; 92.0-136.8) and Cmax,ss was 109.9 (89.6-134.8), Group 3 and 1 of AUC(0-τ),ss was 140.5 (115.9-170.3) and Cmax,ss was 137.8 (112.9-168.2), Group 4 and 1 of AUC(0-τ),ss was 114.2 (90.3-144.4) and Cmax,ss was 120.8 (92.5-157.8), Group 5 and 1 of; AUC(0-τ),ss was 213.0 (153.1-296.3) and Cmax,ss was 123.3 (92.2-164.7) and Group 6 and 1 of AUC(0-τ),ss was 247.4 (197.8-309.6) and Cmax,ss was 95.6 (73.0-125.1). Significant increase in systemic exposure of TMZ was observed in subjects; over 75 year's age and renally impaired compared to healthy subjects. TMZ was safe and well-tolerated.

COX-2 Expression in Breast Carcinoma with Correlation to Clinicopathological Parameters

Objective: Breast carcinoma is the most common malignant tumor and the leading cause of carcinoma deaths in women. Its etiology is multifactorial, implicating reproductive factors, hormonal imbalances and genetic predispositions. Studies have shown that Cycloxygenase-2 (COX-2) plays an important role in the carcinogenesis and increased expression has been regarded as a poor prognostic factor. The objective of our study is 1. To study COX-2 expression in normal breast tissue, DCIS and invasive breast cancer. 2. To determine COX-2 expression with clinicopathological prognostic parameters. Methods: Radical mastectomy specimens were studied for COX-2 expression by immunohistochemistry in 50 patients diagnosed as breast carcinoma. COX-2 expression is quantified as IHS Score and separately calculated for normal breast epithelium near the tumor, DCIS and invasive areas. Relationship between COX-2 expression with various clinicopathological parameters was evaluated. Result: The results of our study suggest an association of the expression of COX-2 to the factors associated with poor prognosis in breast cancer, such as larger tumor size, positive lymph node status, higher T stage and N stage and lymphovascular invasion. There was a higher COX-2 expression in the DCIS component as compared to the invasive ductal carcinoma component and the adjoining breast epithelium. Conclusion: Our study established the role of COX-2 in carcinogenesis and its association with adverse prognostic factors.

Differential Metabolic Effects of Beta-Blockers: an Updated Systematic Review of Nebivolol.

Blood pressure management in hypertensive patients with metabolic abnormalities is challenging, since many of the antihypertensive drugs adversely affect metabolism. Besides effective control of blood pressure in patients with hypertension, third-generation beta-blockers such as nebivolol offer additional benefits for central hemodynamics and neutral or beneficial effects on metabolism. Emerging clinical data suggest that nebivolol also has similar effects on metabolism in obese hypertensive and hypertensive diabetic patients. The present article will provide a systematic analysis of the pathophysiological links among hypertension, insulin resistance, and metabolic syndrome. We will also summarize the available clinical evidence regarding the metabolic effects of beta-blockers in hypertensive patients, with an emphasis on nebivolol. Nebivolol exerts neutral or beneficial effects on insulin sensitivity and lipid metabolism in hypertensive patients, owing to its nitric oxide-mediated vasodilatory and antioxidative properties. Thus, nebivolol could be a favorable therapeutic option for the treatment of hypertension in patients with impaired glucose and lipid metabolism.

Recent Advances in Lipid-Based Vesicles and Particulate Carriers for Topical and Transdermal Application.

In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery, and interest in life cycle management strategies among pharmaceutical companies. Literature review of recent publications indicates that among various skin delivery systems, lipid-based delivery systems (vesicular carriers and lipid particulate systems) have been the most successful. Vesicular carriers consist of liposomes, ultradeformable liposomes, and ethosomes, while lipid particulate systems consist of lipospheres, solid lipid nanoparticles, and nanostructured lipid carriers. These systems can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Considering that lipid-based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations, and regulatory considerations. Therefore, this review article encompasses recent research advances addressing the aforementioned issues.