Takotsubo Cardiomyopathy Triggered by Emotional Stress From the Russia-Ukraine War.

Stress-induced cardiomyopathy presents like acute coronary syndrome and is triggered by emotional stress or critical illness. Increased incidence has been reported during the COVID-19 pandemic and natural disasters. We describe a case of stress-induced cardiomyopathy as an indirect consequence of the Russia-Ukraine war. (Level of Difficulty: Beginner.).

Cardiac Thromboembolism in COVID-19: A Case Series.

Venous thromboembolism (VTE) is a very common complication of coronavirus disease-2019 (COVID-19) because of the acquired hypercoagulability in these patients. Cardiovascular thromboembolism (CTE) is another complication that is relatively rare yet catastrophic. We present two cases of COVID-19 which were complicated by CTE. Case one describes a 55-year-old male with COVID-19 who had an ST-segment elevation myocardial infarction (STEMI) secondary to coronary artery embolism and was also found to have biventricular thrombi (BVT). Case two describes a 65-year-old female presenting with STEMI secondary to coronary artery embolism. This document highlights how CTE can be present in COVID-19 patients and describes the available evidence for its management. Given the paucity of data on these complications, we illustrate the offered treatment which was based on the data extrapolated from the treatment of VTE in COVID-19 and the treatment of CTE in non-COVID-19 patients.

Giant Epicardial Cyst Eroding Left Ventricular Wall Mimicking as Simple Pericardial Cyst.

Epicardial cysts are rarer benign tumors than pericardial cysts. There have been few reports on surgical management of epicardial cysts. A 17-year-old normotensive boy presented with chest pain and palpitations, which on evaluation was found to be a mediastinal mass (pericardial cyst). Surgical resection of the cyst via thoracotomy was planned. The cyst was diagnosed as an epicardial cyst intraoperatively. However, due to the epicardial origin of cyst and posterior adhesions, resection was done via midline approach. The base was formed by visceral pericardium and eroding into myocardium of left ventricle, so the resection was concluded with on-pump surgery. In case of erroneous diagnosis or undesirable finding, a safer midline approach with on-pump surgery, as an alternative to minimally invasive approach for complicated epicardial cysts (erosion into ventricle/lying in close proximity to important structures or near to coronary arteries) should be considered.

Giant Epicardial Cyst Eroding Left Ventricular Wall Mimicking as Simple Pericardial Cyst

Abstract Epicardial cysts are rarer benign tumors than pericardial cysts. There have been few reports on surgical management of epicardial cysts. A 17-year-old normotensive boy presented with chest pain and palpitations, which on evaluation was found to be a mediastinal mass (pericardial cyst). Surgical resection of the cyst via thoracotomy was planned. The cyst was diagnosed as an epicardial cyst intraoperatively. However, due to the epicardial origin of cyst and posterior adhesions, resection was done via midline approach. The base was formed by visceral pericardium and eroding into myocardium of left ventricle, so the resection was concluded with on-pump surgery. In case of erroneous diagnosis or undesirable finding, a safer midline approach with on-pump surgery, as an alternative to minimally invasive approach for complicated epicardial cysts (erosion into ventricle/lying in close proximity to important structures or near to coronary arteries) should be considered.

Impact on patients' compliance with medication using prepacked blisters for multidrug medical therapy: I-COMPLY Study.

PURPOSE: Studies have supported the use of packaging interventions such as pillboxes or blister packs to improve medication adherence but have not evaluated the efficacy of these interventions in a population of low socioeconomic status. The aim of this study was to assess the effect of home-delivered pill packs on medication adherence in a low-income Black American population with Medicaid insurance. METHODS: This study was an open-label, randomized, controlled trial. The patient population studied included 80 patients followed by primary care physicians at the Cleveland Clinic. Patients were randomized to a study group who received delivery of their multidrug medical therapy, defined as a minimum of 4 medications daily, in prepackaged blisters or a control group who obtained their prescriptions from their routine pharmacy. RESULTS: The primary analysis compared the mean percentage of missed pills between the 2 groups using t-test analysis. The percentage of missed pills in the study group was significantly lower than in the control group (mean [SD]: 3.7% [6.0%] vs 17.4% [16.6%] missed daily pills; P < 0.001). The number of daily missed doses was also significantly lower in the study group (0.3 [0.5] vs 0.7 [0.6]; P = 0.002). Patients were on a mean of 8.1 (SD, 2.3) and 8.1 (SD, 2.6) medications in the study and control groups, respectively (P = 0.96). CONCLUSION: Delivery of prepackaged medications in a low-income Black American community was demonstrated to improve medication adherence. The use of prepackaged blisters for medication home delivery is a model that can be utilized on a larger scale for patients on multidrug medical therapy.

Community and healthcare system-related factors feeding the phenomenon of evading medical attention for time-dependent emergencies during COVID-19 crisis.

The current COVID-19 crisis has significantly impacted healthcare systems worldwide. There has been a palpable increase in public avoidance of hospitals, which has interfered in timely care of critical cardiovascular conditions. Complications from late presentation of myocardial infarction, which had become a rarity, resurfaced during the pandemic. We present two such encounters that occurred due to delay in seeking medical care following myocardial infarction due to the fear of contracting COVID-19 in the hospital. Moreover, a comprehensive review of literature is performed to illustrate the potential factors delaying and decreasing timely presentations and interventions for time-dependent medical emergencies like ST-segment elevation myocardial infarction (STEMI). We emphasise that clinicians should remain vigilant of encountering rare and catastrophic complications of STEMI during this current era of COVID-19 pandemic.

Van Neck-Odelberg Disease: A Rare Case Report.

INTRODUCTION: Pain in groin without any history of trauma or positive clinical findings of infection or stress fracture in ischiopubic ramus poses challenges in diagnosis of the condition in prepubertal age. "Osteochondrosis of ischiopubic synchondrosis (IPS)" also called as "Van Neck-Odelberg" disease. Left leg dominant patient presented with pain in groin and limping with left leg dominance. Differential diagnosis - such as stress fractures, osteomyelitis, tuberculosis, post-traumatic osteolysis, or any neoplasia - is need be ruled out to arrive at diagnosis. The literature is reviewed with modern technologies for diagnosis of the same. CASE REPORT: A 12-year-old, left limb dominant boy with tenderness in the right groin as the only clinical finding and sclerotic shadow over ischiopubic region on X-ray posed a challenge for diagnosis. With further studies by computed tomography and magnetic resonance imaging diagnosis was done. Hence, we are presenting a case labeled as Van Neck-Odelberg disease. CONCLUSION: Diagnosis of Van Neck-Odelberg disease is a challenging diagnosis. Other conditions such as post-traumatic osteolysis, osteomyelitis, and stress fractures in prepubertal age need to be ruled out. Clinical symptoms must be present to label it as osteochondritis of IPS on radiographs as unilateral delayed fusion of the same is a physiological process in asymptomatic cases.

Pacemaker and Defibrillator Implantation in Patients with Transposition of the Great Arteries.

Transposition of the great arteries (TGA) is represented in 5% to 7% of patients with congenital heart disease. These patients face a significant burden of arrhythmia and sudden cardiac death throughout their lives, and many eventually undergo pacemaker or cardiac-defibrillator implantation. Outcomes data following device implantation in this population, however, are limited. From an electrophysiologic database at a large, tertiary care medical center, we identified 63 TGA patients (34 with dextro (d)-TGA and 29 with levo (l)-TGA) with systemic right ventricles receiving an implantable cardiac device from 1996 to 2014. Medical records were reviewed for demographic, echocardiography and device interrogation data. Overall, l-TGA patients were older than d-TGA patients when they underwent initial device implantation (35.6 ± 18.2 versus 17.3 ± 10.6 years, p<0.001), and had more concomitant cardiac defects (55% versus 12%, p<0.001). Survival following initial device implantation was similar between l-TGA and d-TGA (72% versus 74%, p = 1.00), despite the baseline difference in age. Twenty-four patients underwent implantable cardioverter-defibrillator (ICD) implantation: 18 for primary intervention (11 l-TGA and seven d-TGA), and six for secondary prevention (four l-TGA and two d-TGA). Sixty-seven percent of patients in the secondary prevention group had appropriate shocks, compared with 0% of primary prevention patients. Patients with ICD discharge were more likely to have concomitant heart defects (100% versus 30%, p = 0.011). Despite being significantly younger, d-TGA patients had similar survival rates following device implant to l-TGA patients. Patients with TGA and sustained ventricular arrhythmias are at high risk for subsequent events, and typically benefit from ICD implantation. The role of prophylactic ICD implantation in this population, however, remains uncertain.

Utility of Glycated Hemoglobin for Assessment of Glucose Metabolism in Patients With ST-Segment Elevation Myocardial Infarction.

Glycated hemoglobin (HbA1c) is an approved and widely used laboratory investigation for diagnosis of diabetes that is not affected by acute changes in blood glucose. Our aim was to analyze the extent to which routine HbA1c measurements diagnose unknown diabetes mellitus (DM) in patients presenting with ST-segment elevation myocardial infarction (STEMI). We also compared outcomes in patients with newly diagnosed DM, previously established DM and those without DM. Consecutive patients undergoing PCI for STEMI from January 2005 to December 2012 were included and routinely performed admission HbA1c was used to identify patients with previously undiagnosed DM (HbA1c ≥6.5 and no history of DM or DM therapy) and pre-DM (HbA1c 5.7% to 6.4%). Overall 1,686 consecutive patients underwent primary percutaneous coronary intervention for STEMI during the study period and follow-up data were available for 1,566 patients (90%). A quarter of the patients (24%, n = 405) had history of DM, 7% (n = 118) had previously undiagnosed DM, and 38.7% (n = 652) had pre-DM. Mortality was comparable in patients with known DM and newly diagnosed DM both in-hospital (11.1% vs 11.9%, p = 0.87) and at 3-year follow-up (27.3% and 24%). Patients with DM, including those who were newly diagnosed, had higher mortality at 3 years (26.5%) compared to those with pre-DM (12.1%) or no dysglycemia (11.2%, p <0.01). In conclusion, a substantial number of patients with STEMI have previously undiagnosed DM (7%). These patients have similar in-hospital and long-term mortality as those with known DM, and outcomes are inferior to patients without dysglycemia.

Probability of developing proximal deep-vein thrombosis and/or pulmonary embolism after distal deep-vein thrombosis.

Isolated distal deep-vein thrombosis (DDVT) of the lower extremities can be associated with subsequent proximal deep-vein thrombosis (PDVT) and/or acute pulmonary embolism (PE). We aimed to develop a model predicting the probability of developing PDVT and/or PE within three months after an isolated episode of DDVT. We conducted a retrospective cohort study of patients with symptomatic DDVT confirmed by lower extremity vein ultrasounds between 2001-2012 in the Cleveland Clinic Health System. We reviewed all the ultrasounds, chest ventilation/perfusion and computed tomography scans ordered within three months after the initial DDVT to determine the incidence of PDVT and/or PE. A multiple logistic regression model was built to predict the rate of developing these complications. The final model included 450 patients with isolated DDVT. Within three months, 30 (7 %) patients developed an episode of PDVT and/or PE. Only two factors predicted subsequent thromboembolic complications: inpatient status (OR, 6.38; 95 % CI, 2.17 to 18.78) and age (OR, 1.02 per year; 95 % CI, 0.99 to 1.05). The final model had a bootstrap bias-corrected c-statistic of 0.72 with a 95 % CI (0.64 to 0.79). Outpatients were at low risk (< 4 %) of developing PDVT/PE. Inpatients aged ≥ 60 years were at high risk (> 10 %). Inpatients aged < 60 were at intermediate risk. We created a simple model that can be used to risk stratify patients with isolated DDVT based on inpatient status and age. The model might be used to choose between anticoagulation and monitoring with serial ultrasounds.

Duodenal villous morphology assessed using magnification narrow band imaging correlates well with histology in patients with suspected malabsorption syndrome.

BACKGROUND AND AIM: Narrow band imaging with magnification enables detailed assessment of duodenal villi and may be useful in predicting the presence of villous atrophy or normal villi. We aimed to assess the morphology of duodenal villi using magnification narrow band imaging and correlate it with histology findings in patients with clinically suspected malabsorption syndrome. METHODS: Patients with clinical suspicion of malabsorption presenting at a tertiary care center were prospectively recruited in this diagnostic intervention study. Patients underwent upper gastrointestinal endoscopy using magnification narrow band imaging. The villous morphology in the second part of the duodenum was assessed independently by two endoscopists and the presence of normal or atrophic villi was recorded. Biopsy specimen was obtained from the same area and was examined by two pathologists together. The sensitivity and specificity of magnification narrow band imaging in detecting the presence of duodenal villous atrophy was calculated and compared to the histology. RESULTS: One hundred patients with clinically suspected malabsorption were included in this study. Sixteen patients had histologically confirmed villous atrophy. The sensitivity and specificity of narrow band imaging in predicting villous atrophy was 87.5% and 95.2%, respectively, for one endoscopist. The corresponding figures for the second endoscopist were 81.3% and 92.9%, respectively. The interobserver agreement was very good with a kappa value of 0.87. CONCLUSION: Magnification narrow band imaging performed very well in predicting duodenal villous morphology. This may help in carrying out targeted biopsies and avoiding unnecessary biopsies in patients with suspected malabsorption.

Solid-state NMR analysis of membrane proteins and protein aggregates by proton detected spectroscopy.

Solid-state NMR has emerged as an important tool for structural biology and chemistry, capable of solving atomic-resolution structures for proteins in membrane-bound and aggregated states. Proton detection methods have been recently realized under fast magic-angle spinning conditions, providing large sensitivity enhancements for efficient examination of uniformly labeled proteins. The first and often most challenging step of protein structure determination by NMR is the site-specific resonance assignment. Here we demonstrate resonance assignments based on high-sensitivity proton-detected three-dimensional experiments for samples of different physical states, including a fully-protonated small protein (GB1, 6 kDa), a deuterated microcrystalline protein (DsbA, 21 kDa), a membrane protein (DsbB, 20 kDa) prepared in a lipid environment, and the extended core of a fibrillar protein (α-synuclein, 14 kDa). In our implementation of these experiments, including CONH, CO(CA)NH, CANH, CA(CO)NH, CBCANH, and CBCA(CO)NH, dipolar-based polarization transfer methods have been chosen for optimal efficiency for relatively high protonation levels (full protonation or 100 % amide proton), fast magic-angle spinning conditions (40 kHz) and moderate proton decoupling power levels. Each H-N pair correlates exclusively to either intra- or inter-residue carbons, but not both, to maximize spectral resolution. Experiment time can be reduced by at least a factor of 10 by using proton detection in comparison to carbon detection. These high-sensitivity experiments are especially important for membrane proteins, which often have rather low expression yield. Proton-detection based experiments are expected to play an important role in accelerating protein structure elucidation by solid-state NMR with the improved sensitivity and resolution.

Intraductal Hepatocellular Carcinoma without Parenchymal Tumor: A Case Report.

INTRODUCTION: Obstructive jaundice due to hepatocellular carcinoma is rare. We present a case of hepatocellular carcinoma presenting as an intraductal tumor, which was clinically and radiologically diagnosed as cholangiocarcinoma. CLINICAL PRESENTATION: A 59-year-old male was admitted with recurrent episodes of jaundice. He was found to have a tumor in the right hepatic duct extending into intrahepatic ducts, which was clinically and radiologically diagnosed as cholangiocarcinoma. RESULTS: The patient underwent right hepatectomy with excision of the bile duct and left hepaticojejunostomy. Histological examination revealed an intraductal moderately differentiated hepatocellular carcinoma. The rest of the liver parenchyma showed features secondary to biliary obstruction but no tumor. CONCLUSION: A case of hepatocellular carcinoma presenting as an intraductal tumor with obstructive jaundice and no evidence of parenchymal tumor is presented.

NMR Determination of Protein pK(a) Values in the Solid State.

Charged residues play an important role in defining key mechanistic features in many biomolecules. Determining the pK(a) values of large, membrane or fibrillar proteins can be challenging with traditional methods. In this study we show how solid-state NMR is used to monitor chemical shift changes during a pH titration for the small soluble ß1 immunoglobulin binding domain of protein G. The chemical shifts of all the amino acids with charged side-chains throughout the uniformly-(13)C,(15)N-labeled protein were monitored over several samples varying in pH; pK(a) values were determined from these shifts for E27, D36, and E42, and the bounds for the pK(a) of other acidic side-chain resonances were determined. Additionally, this study shows how the calculated pK(a) values give insights into the crystal packing of the protein.

Atomic resolution protein structure determination by three-dimensional transferred echo double resonance solid-state nuclear magnetic resonance spectroscopy.

We show that quantitative internuclear (15)N-(13)C distances can be obtained in sufficient quantity to determine a complete, high-resolution structure of a moderately sized protein by magic-angle spinning solid-state NMR spectroscopy. The three-dimensional ZF-TEDOR pulse sequence is employed in combination with sparse labeling of (13)C sites in the beta1 domain of the immunoglobulin binding protein G (GB1), as obtained by bacterial expression with 1,3-(13)C or 2-(13)C-glycerol as the (13)C source. Quantitative dipolar trajectories are extracted from two-dimensional (15)N-(13)C planes, in which approximately 750 cross peaks are resolved. The experimental data are fit to exact theoretical trajectories for spin clusters (consisting of one (13)C and several (15)N each), yielding quantitative precision as good as 0.1 A for approximately 350 sites, better than 0.3 A for another 150, and approximately 1.0 A for 150 distances in the range of 5-8 A. Along with isotropic chemical shift-based (TALOS) dihedral angle restraints, the distance restraints are incorporated into simulated annealing calculations to yield a highly precise structure (backbone RMSD of 0.25+/-0.09 A), which also demonstrates excellent agreement with the most closely related crystal structure of GB1 (2QMT, bbRMSD 0.79+/-0.03 A). Moreover, side chain heavy atoms are well restrained (0.76+/-0.06 A total heavy atom RMSD). These results demonstrate for the first time that quantitative internuclear distances can be measured throughout an entire solid protein to yield an atomic-resolution structure.

Proton-detected solid-state NMR spectroscopy of natural-abundance peptide and protein pharmaceuticals.

The natural way: A sensitive NMR spectroscopic method is developed to obtain well-resolved two-dimensional spectra ((15)N-(1)H and (13)C-(1)H) for natural-abundance (that is, without the need for isotopic enrichment) large-molecule samples, such as biopharmaceuticals. This method gives structural insights on two lyophilized aprotinin samples and three insulin samples in lyophilized, microcrystalline suspension formulation (red; see picture) and fibril (green) forms.

Dipole tensor-based atomic-resolution structure determination of a nanocrystalline protein by solid-state NMR.

Magic-angle spinning (MAS) solid-state NMR (SSNMR) techniques have emerged in recent years for solving complete structures of uniformly labeled proteins lacking macroscopic order. Strategies used thus far have relied primarily on semiquantitative distance restraints, analogous to the nuclear Overhauser effect (NOE) routinely used in solution NMR. Here, we present a complementary approach for using relative orientations of molecular fragments, determined from dipolar line shapes. Whereas SSNMR distance restraints typically have an uncertainty of approximately 1 A, the tensor-based experiments report on relative vector (pseudobond) angles with precision of a few degrees. By using 3D techniques of this type, vector angle (VEAN) restraints were determined for the majority of the 56-residue B1 immunoglobulin binding domain of protein G [protein GB1 (a total of 47 HN-HN, 49 HN-HC, and 12 HA-HB restraints)]. By using distance restraints alone in the structure calculations, the overall backbone root-mean-square deviation (bbRMSD) was 1.01 +/- 0.13 A (1.52 +/- 0.12 A for all heavy atoms), which improved to 0.49 +/- 0.05 A (1.19 +/- 0.07 A) on the addition of empirical chemical shift [torsion angle likelihood obtained from shift and sequence similarity (TALOS)] restraints. VEAN restraints further improved the ensemble to 0.31 +/- 0.06 A bbRMSD (1.06 +/- 0.07 A); relative to the structure with distances alone, most of the improvement remained (bbRMSD 0.64 +/- 0.09 A; 1.29 +/- 0.07 A) when TALOS restraints were removed before refinement. These results represent significant progress toward atomic-resolution protein structure determination by SSNMR, capabilities that can be applied to a large range of membrane proteins and fibrils, which are often not amenable to solution NMR or x-ray crystallography.

Proton-detected solid-state NMR spectroscopy of fully protonated proteins at 40 kHz magic-angle spinning.

Remarkable progress in solid-state NMR has enabled complete structure determination of uniformly labeled proteins in the size range of 5-10 kDa. Expanding these applications to larger or mass-limited systems requires further improvements in spectral sensitivity, for which inverse detection of 13C and 15N signals with 1H is one promising approach. Proton detection has previously been demonstrated to offer sensitivity benefits in the limit of sparse protonation or with approximately 30 kHz magic-angle spinning (MAS). Here we focus on experimental schemes for proteins with approximately 100% protonation. Full protonation simplifies sample preparation and permits more complete chemical shift information to be obtained from a single sample. We demonstrate experimental schemes using the fully protonated, uniformly 13C,15N-labeled protein GB1 at 40 kHz MAS rate with 1.6-mm rotors. At 500 MHz proton frequency, 1-ppm proton line widths were observed (500 +/- 150 Hz), and the sensitivity was enhanced by 3 and 4 times, respectively, versus direct 13C and 15N detection. The enhanced sensitivity enabled a family of 3D experiments for spectral assignment to be performed in a time-efficient manner with less than a micromole of protein. CANH, CONH, and NCAH 3D spectra provided sufficient resolution and sensitivity to make full backbone and partial side-chain proton assignments. At 750 MHz proton frequency and 40 kHz MAS rate, proton line widths improve further in an absolute sense (360 +/- 115 Hz). Sensitivity and resolution increase in a better than linear manner with increasing magnetic field, resulting in 14 times greater sensitivity for 1H detection relative to that of 15N detection.