Significance of silent myocardial ischemia during exercise testing in patients with coronary artery disease

To evaluate the significance of ischemic ST-segment depression without associated chest pain during exercise testing, data were analyzed from 2,982 patients from the Coronary Artery Surgery Study (CASS) registry who underwent coronary arteriography and exercise testing and were followed up for 7 years. Patients with proved coronary artery disease (CAD) (at least 70% diameter narrowing) were grouped according to whether they had at least 1 mm of ST-segment depression or anginal chest pain during exercise testing. Four hundred twenty-four had ischemic ST depression without angina (group 1); 232 had angina but no ischemic ST depression (group 2); 456 had both ischemic ST depression and angina (group 3); and 471 had neither ischemic ST depression nor angina (group 4). Sixty-three percent of patients in group 1 and 55% in group 2 had multivessel CAD (difference not significant). The 7-year survival rates were similar for patients in groups 1 (76%), 2 (77%), and 3 (78%), but were significantly better for patients in group 4 (88%, p less than 0.001). Among group 1 patients, survival was related to severity of CAD (p less than 0.001). The 7-year survival rate in group 1 was significantly worse than that in a separate group of 282 patients with ischemic ST depression without angina during exercise testing who had no CAD (95% survival, p less than 0.001). Thus, in patients with silent myocardial ischemia during exercise testing, the extent of CAD and the 7-year survival rate are similar to those of patients with angina during exercise testing. Prognosis is determined primarily by the severity of CAD. In patients without CAD, the survival rate is excellent.     

Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity

Pre-B cell colony-enhancing factor (PBEF), also known as visfatin, is a highly conserved, 52-kDa protein found in living species from bacteria to humans. Originally a curiosity identified serendipitously in microarray studies but having no obvious functional importance, PBEF has now been shown to exert three distinct activities of central importance to cellular energetics and innate immunity. Within the cell, PBEF functions as a nicotinamide phosphoribosyl transferase, the rate-limiting step in a salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. By virtue of this role, it can regulate cellular levels of NAD and so impact not only cellular energetics but also NAD-dependent enzymes such as sirtuins. Although it lacks a signal peptide, PBEF is released by a variety of cells, and elevated levels can be found in the systemic circulation of patients with a variety of inflammatory diseases. As an extracellular cytokine, PBEF can induce the cellular expression of inflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6. Finally, PBEF has been shown to be an adipokine expressed by fat cells that exerts a number of insulin mimetic and antagonistic effects. PBEF expression is up-regulated in a variety of acute and chronic inflammatory diseases including sepsis, acute lung injury, rheumatoid arthritis, inflammatory bowel disease, and myocardial infarction and plays a key role in the persistence of inflammation through its capacity to inhibit neutrophil apoptosis. This review summarizes the admittedly incomplete body of emerging knowledge about a remarkable new mediator of innate immunity.     

An efficient method for the derivation of mouse embryonic stem cells

Mouse embryonic stem cells (mESCs) represent a unique tool for many researchers; however, the process of ESC derivation is often very inefficient and requires high specialization, training, and expertise. To circumvent these limitations, we aimed to develop a simple and efficient protocol based on the use of commercially available products. Here, we present an optimized protocol that we successfully applied to derive ESCs from several knockout mouse strains (Wnt-1, Wnt-5a, Lrp6, and parkin) with 50%-75% efficiency. The methodology is based on the use of mouse embryonic fibroblast feeders, knockout serum replacement (SR), and minimal handling of the blastocyst. In this protocol, all centrifugation steps (as well as the use of trypsin inhibitor) were avoided and replaced by an ESC medium containing fetal calf serum (FCS) after the trypsinizations. We define the potential advantages and disadvantages of using SR and FCS in individual steps of the protocol. We also characterize the ESCs for the expression of ESC markers by immunohistochemistry, Western blot, and a stem cell focused microarray. In summary, we provide a simplified and improved protocol to derive mESCs that can be useful for laboratories aiming to isolate transgenic mESCs for the first time.     

Red cell distribution width is a potent prognostic parameter for in-hospital and post-discharge mortality in hospitalized coronavirus disease 2019 patients: a registry-based cohort study on 3941 patients

AimTo investigate clinical and prognostic associations of red cell distribution width (RDW) in hospitalized coronavirus disease 2019 (COVID-19) patients.MethodsWe retrospectively analyzed the records of 3941 consecutive COVID-19 patients admitted to a tertiary-level institution from March 2020 to March 2021 who had available RDW on admission.ResultsThe median age was 74 years. The median Charlson comorbidity index (CCI) was 4. The majority of patients (84.1%) on admission presented with severe or critical COVID-19. Patients with higher RDW were significantly more likely to be older and female, to present earlier during infection, and to have higher comorbidity burden, worse functional status, and critical presentation of COVID-19 on admission. RDW was not significantly associated with C-reactive protein, occurrence of pneumonia, or need for oxygen supplementation on admission. During hospital stay, patients with higher RDW were significantly more likely to require high-flow oxygen therapy, mechanical ventilation, intensive care unit, and to experience prolonged immobilization, venous thromboembolism, bleeding, and bacterial sepsis. Thirty-day and post-hospital discharge mortality gradually increased with each rising RDW percent-point. In a series of multivariate Cox-regression models, RDW demonstrated robust prognostic properties at >14% cut-off level. This cut-off was associated with inferior 30-day and post-discharge survival independently of COVID-19 severity, age, and CCI; and with 30-day survival independently of COVID severity and established prognostic scores (CURB-65, 4C-mortality, COVID-gram and VACO-index).ConclusionRDW has a complex relationship with COVID-19-associated inflammatory state and is affected by prior comorbidities. RDW can improve the prognostication in hospitalized COVID-19 patients.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a systemic infectious disease usually presenting with fever and respiratory symptoms (1). Although the most frequent serious manifestation of COVID-19 is pneumonia, the disease has been associated with cardiovascular, neurological, and gastrointestinal symptoms (2). Systemic inflammatory response mediated by high interleukin-6 concentrations induced by SARS-CoV-2 infection is associated with more severe clinical presentation, respiratory deterioration, and death (3,4). The presence of prior chronic comorbidities substantially affects the survival of COVID-19 patients (1).Anisocytosis, ie, unequal red blood cells (RBC) size, is a sensitive marker of distress in erythropoiesis or RBC destruction. It can be induced by various metabolic and inflammatory stimuli, nutrient deficiencies, infections, spleen disorders, and specific drugs interfering with RBC production (5). Anisocytosis can be quantified as a coefficient of variation of mean cell volume termed red blood cell distribution width (RDW), which is obtained by automatic cell counters. Higher RDW levels have recently gained attention as they are uniformly associated with unfavorable presentation and inferior outcomes in many chronic metabolic and malignant diseases (6-12). More severe clinical presentation and higher mortality rates were also found in COVID-19 patients with higher RDW levels (13-16). However, an association of RDW with other clinical outcomes in hospitalized COVID-19 patients, as well as the relationship with increased mortality in the context of other established prognostic scores, are not well defined. Thus, we aimed to investigate clinical and prognostic significance of RDW in a large cohort of hospitalized COVID-19 patients from our institution. We hypothesized that RDW was associated with more severe COVID-19 on admission and higher death rate.     

Early results after minimal lobectomy for benign nodular goiter

Following traditional operations (enucleation and subtotal resection) for benign nodular goiters recurrences may develop. Reoperations for this condition can cause complications, such as hypoparathyroidism and damage of the recurrent laryngeal nerve. That is why total thyroidectomy is recommended by many specialists in benign thyroid disease. We performed lobectomy on one side, and, if necessary, partial resection on the other side. Lobectomy was performed on one side in 31 cases, with partial resections on the other side in 73 patients. We tried to identify the parathyroid glands and both recurrent laryngeal nerves. Postoperative complications were evaluated. Temporary dysfunction of the recurrent laryngeal nerve was detected in 2.3%, permanent damage in 1.1%. Temporary hypocalcaemia developed in 16.4%, permanent hypocalcemia in 1.9%. Two reoperations were necessary for bleeding. Because of the low postoperative complication rate we recommend this method as an alternative to thyroidectomy for benign nodular goiters. We know that our favourable results can be compared with traditional subtotal resection and thyroidectomy when long term results of thyroid function and data about nodular recurrences will be collected.     

Modified Split‐Cast Technique: A New,Timesaving Clinical Remount Technique

Interocclusal discrepancies can be eliminated by a clinical remount procedure, but most practitioners avoid it because of the time involved. This article introduces a new timesaving method, the modified split‐cast technique. It uses a semi‐adjustable articulator, tin foil as plaster separator, and an addition‐type, silicone bite‐registration material. The technician does most of the remounting procedures before the denture delivery appointment, so the dentist spends very little time chairside to complete the clinical remount procedure. Compared with the conventional and two other remounting techniques, the new technique is faster and easier to manipulate.     

Exploratory Study of Apparent Diffusion Coefficient Histogram Metrics in Assessing Pancreatic Malignancy

PurposeTo evaluate whole-lesion 3D-histogram apparent diffusion coefficient (ADC) metrics for assessment of pancreatic malignancy.MethodsForty-two pancreatic malignancies (36 pancreatic adenocarcinoma [PDAC], 6 pancreatic neuroendocrine [PanNET]) underwent abdominal magnetic resonance imaging (MRI) with diffusion-weighted imaging before endoscopic ultrasound biopsy or surgical resection. Two radiologists independently placed 3D volumes of interest to derive whole-lesion histogram ADC metrics. Mann-Whitney tests and receiver operating characteristic analyses were used to assess metrics’ diagnostic performance for lesion histology, T-stage, N-stage, and grade.ResultsWhole-lesion ADC histogram metrics lower in PDACs than PanNETs for both readers (P ≤ .026) were mean ADC (area under the curve [AUC] = 0.787-0.792), mean of the bottom 10th percentile (mean_0-10) (AUC = 0.787-0.880), mean of the 10th-25th percentile (mean_10-25) (AUC = 0.884-0.917) and mean of the 25th-50th percentile (mean_25-50) (AUC = 0.829-0.829). For mean_10-25 (metric with highest AUC for identifying PDAC), for reader 1 a threshold > 0.94 × 10^?3 mm²/s achieved sensitivity 94% and specificity 83%, and for reader 2 a threshold > 0.82 achieved sensitivity 97% and specificity 67%. Metrics lower in nodal status ≥ N₁ than N₀ for both readers (P ≤ .043) were mean_0-10 (AUC = 0.789-0.822) and mean_10-25 (AUC = 0.800-0.822). For mean_10-25 (metric with highest AUC for identifying N₀), for reader 1 a threshold <1.17 achieved sensitivity 87% and specificity 67%, and for reader 2 a threshold <1.04 achieved sensitivity 87% and specificity 83%. No metric was associated with T-stage (P > .195) or grade (P > .215).ConclusionVolumetric ADC histogram metrics may serve as non-invasive biomarkers of pancreatic malignancy. Mean_10-25 outperformed standard mean for lesion histology and nodal status, supporting the role of histogram analysis.     

Pathways from Positive,Negative, and Specific Alcohol Expectancies to Weekday and Weekend Drinking to Alcohol Problems

Prevention Science - The current study tested and identified risk and protective pathways from alcohol expectancies to weekday and weekend consumption to problematic consequences. Adult alcohol...     

Efficacy and safety of diphenylcyclopropenone among Chinese patients with steroid resistant and extensive alopecia areata

Background Topical immunotherapy has recently been found useful in the treatment of chronic and extensive Alopecia Areata (AA). Objective To evaluate the efficacy and safety of diphenylcyclopropenone (DPCP) use among Chinese patients with steroid resistant and extensive AA in our institute. Methods The medical records of 31 Chinese patients treated with DPCP were analysed retrospectively. The efficacy, adverse effects, and relapse rate of DPCP treatment were reviewed. Results Thirty‐one (16 male, 15 female) Chinese patients with extensive, steroid resistant Alopecia Areata and a mean age of 28.9 years (SE 10.4) were treated. The mean age of onset was 17.8 years (SE 8.8) with an average disease duration of 11.2 years (SE 7.7). Ten patients had a history of atopy and 4 had a history of thyroid disease. Nail changes were found in 14 patients and a family history of AA was found in 2 patients. Thirteen patients (41.9%) had experienced total hair loss. Two patients abandoned the treatment due to severe side effects. Of the remaining 29 patients, 4 (13.8%), 7 (24.1%), 5 (17.2%), and 13 (44.8%) achieved >90% complete response, >50–90% partial response, >10–50% minimal response, and <10% no response hair regrowth, respectively. Adverse effects included pruritus, erythema, vesiculation, scaling, cervical lymphadenopathy, dyspigmentation and urticarial reactions. Relapse occurred (>25% hair loss) in 69.23% of patients after 18 months of follow up. Conclusions DPCP is an effective and tolerable treatment for Chinese patients with extensive, steroid resistant AA.