Exercise capacity as an independent risk factor for adverse cardiovascular outcomes among nondiabetic and diabetic patients

Introduction

To investigate if decreased exercise capacity is an independent risk factor for major adverse cardiovascular events (MACE) in diabetics and nondiabetics.

Material and methods

The association of decreased exercise capacity (EC) during a treadmill exercise sestamibi stress test with MACE was investigated in 490 nondiabetics and 404 diabetics. Mean follow-up was 53 months.

Results

Nondiabetics with a predicted EC < 85% had a higher prevalence of myocardial ischemia (34% vs. 19%, p = 0.0002), 2- or 3-vessel obstructive coronary artery disease (CAD) (31% vs. 13%, p = 0.016), myocardial infarction (MI) (17% vs. 7%, p = 0.0005), stroke (8% vs. 2%, p = 0.002), death (11% vs. 3%, p = 0.0002), and MI or stroke or death at follow-up (32% vs. 11%, p < 0.001) compared to nondiabetics with a predicted EC ≥ 85%. Diabetics with a predicted EC < 85% had a higher prevalence of myocardial ischemia (48% vs. 32%, p = 0.0009), 2- or 3-vessel obstructive CAD (54% vs. 28%, p = 0.001), MI (32% vs. 14%, p < 0.001), stroke (22% vs. 6%, p < 0.001), death (17% vs. 9%, p = 0.031), and MI or stroke or death at follow-up (65% vs. 27%, p < 0.001). Stepwise Cox regression analysis showed decreased EC was an independent and significant risk factor for MACE among nondiabetics (hazard ratio 3.3, p < 0.0001) and diabetics (hazard ratio 2.7, p < 0.0001).

Conclusions

Diabetics and nondiabetics with decreased EC were at increased risk for MACE with nondiabetics and decreased EC at similar risk as diabetics with normal EC.     

Surgical Outcomes of Neoscrotal Augmentation with Testicular Prostheses in Transgender Men

IntroductionTesticular prosthesis implantation may be used for neoscrotal augmentation in transgender men.AimAssess the clinical outcomes and risk factors for postoperative complications of this procedure in transgender men.MethodsAll transgender men who underwent neoscrotal augmentation with testicular implants between January 1992 and December 2018 were retrospectively identified. A retrospective chart study was performed that recorded surgical characteristics and postoperative complications. Risk factors on complications were identified using uni- and multivariate analyses.Main Outcome MeasureSurgical outcomes included explantation due to infection, extrusion, discomfort, or leakage.ResultsWe identified 206 patients, and the following prostheses were placed: Dow Corning (n = 22), Eurosilicone (n = 2), Nagor (n = 205), Polytech (n = 10), Promedon (n = 105) , Prometel (n = 22), Sebbin (n = 44), and unknown (n = 2). The mean clinical follow-up time was 11.5 ± 8.3 years. In 43 patients (20.8%), one or both prostheses were explanted due to infection, extrusion, discomfort, prosthesis leakage, or urethral problems. Currently, scrotoplasty according to Hoebeke is the most frequently performed technique. Our review found that for this technique explantation occurred in 6 of 52 patients (11.5%). A history of smoking was a risk factor for postoperative infections and prosthesis explantation. In earlier years, larger prostheses were immediately placed at scrotal reconstruction; however, a trend can be seen toward smaller and lighter testicular prostheses and delayed implantation.Clinical ImplicationsPatients wanting to undergo this procedure can be adequately informed on postoperative outcomes.Strengths & LimitationsStrengths of this study include the number of patients, long clinical follow-up time, and completeness of data. Weaknesses of this study include its retrospective nature and the high variability of prostheses and surgical techniques used.ConclusionOver the years, scrotoplasty techniques and testicular prostheses preferences have changed. Explantation rates have dropped over the last decade.Pigot GLS, Al-Tamimi M, Ronkes B, et al. Surgical Outcomes of Neoscrotal Augmentation with Testicular Prostheses in Transgender Men. J Sex Med 2019;16:1664–1671.     

Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease

BACKGROUND: Refractory celiac disease (RCD) patients with aberrant, often clonal, intraepithelial T-cells are at high risk for development of enteropathy associated T-cell lymphoma (EATL). Early detection of those patients that actually develop EATL is of utmost importance for curative intervention. AIM: First, to establish an optimal cut-off value for the percentage of aberrant lymphocytes, previously determined based on clinical observations, via reference ranges for aberrant T-cells in the duodenal mucosa of celiac disease patient and control groups. Secondly, to compare aberrancy with intestinal T-cell clonality as a prognostic parameter for EATL development in RCD. METHODS: Immunophenotyping using flow cytometry was performed on small intestinal biopsy-derived lymphocytes, obtained from distinct celiac disease (CD) patient and control groups (N=167 in total). T-cell clonality in duodenal biopsy specimens was assessed by PCR in RCD, ulcerative jejunitis and EATL patients (N=31 in total). RESULTS: In 95% of non-refractory CD patients, the highest percentage aberrant T-cells was 20%. Using this cut-off value, EATL development was exclusively seen in RCD with more than 20% aberrant T-cells (median 52% aberrant T-cells, range 27-94%). When compared with T-cell clonality analysis, >20% aberrancy showed a much higher negative predictive value and sensitivity (both 100%) for EATL development in RCD patients than T-cell clonality analysis (respectively 75% and 78%). CONCLUSIONS: Quantification of aberrant T-cells by flow cytometry is preferable to T-cell clonality analysis for identification of RCD patients at risk for EATL development. A cut-off value of 20% is of use in risk stratification, therapeutic options and subsequent follow-up of RCD patients.     

Comparison of demographic and clinical characteristics of hospitalized COVID-19 patients with severe/critical illness in the first wave versus the second wave

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65–157) vs. 87 mg/L (IQR: 39–140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.     

Selected amino acid changes in HIV-1 subtype-C gp41 are associated with specific gp120(V3) signatures in the regulation of co-receptor usage

The majority of studies have characterized the tropism of HIV-1 subtype-B isolates, but little is known about the determinants of tropism in other subtypes. So, the goal of the present study was to genetically characterize the envelope of viral proteins in terms of co-receptor usage by analyzing 356 full-length env sequences derived from HIV-1 subtype-C infected individuals. The co-receptor usage of V3 sequences was inferred by using the Geno2Pheno and PSSM algorithms, and also analyzed to the "11/25 rule". All reported env sequences were also analyzed with regard to N-linked glycosylation sites, net charge and hydrophilicity, as well as the binomial correlation phi coefficient to assess covariation among gp120(V3) and gp41 signatures and the average linkage hierarchical agglomerative clustering were also performed. Among env sequences present in Los Alamos Database, 255 and 101 sequences predicted as CCR5 and CXCR4 were selected, respectively. The classical V3 signatures at positions 11 and 25, and other specific V3 and gp41 amino acid changes were found statistically associated with different co-receptor usage. Furthermore, several statistically significant associations between V3 and gp41 signatures were also observed. The dendrogram topology showed a cluster associated with CCR5-usage composed by five gp41 mutated positions, A22V, R133M, E136G, N140L, and N166Q that clustered with T2V(V3) and G24T(V3) (bootstrap=1). Conversely, a heterogeneous cluster with CXCR4-usage, involving S11GR(V3), 13-14insIG/LG(V3), P16RQ(V3), Q18KR(V3), F20ILV(V3), D25KRQ(V3), Q32KR(V3) along with A30T(gp41), S107N(gp41), D148E(gp41), A189S(gp41) was identified (bootstrap=0.86). Our results show that as observed for HIV-1 subtype-B, also in subtype-C specific and different gp41 and gp120V3 amino acid changes are associated individually or together with CXCR4 and/or CCR5 usage. These findings strengthen previous observations that determinants of tropism may also reside in the gp41 protein.     

Comparison of the two blood culture systems, Bactec 9240 and BacT/Alert 3D, in the detection of Candida spp. and bacteria with polymicrobial sepsis

The purpose of this investigation was to evaluate the performance of the Bactec 9240 and BacT/Alert 3D blood culture systems in the detection of Candida spp. and bacteria in simulated polymicrobial sepsis models. A total of 28 clinical isolates of Escherichia coli, Staphylococcus aureus, Candida albicans, and Candida glabrata were studied. Five polymicrobial models of C. albicans + S. aureus, C. albicans + E. coli, C. glabrata + S. aureus, C. glabrata + E. coli, and C. albicans + C. glabrata were prepared. Each combination was inoculated in five different blood culture vials. The two systems were compared for culture positivity and time to detection (TTD). Twenty-four mixed cultures with a yeast and a bacteria were tested. Bactec Mycosis vials could detect yeasts in all 24 cultures. The aerobic vials from both Bactec and BacT/Alert could detect both yeasts and bacteria in 22/24 (91.66?%) cultures. Bactec Plus Anaerobic/F and BacT/Alert FN vials could detect both microorganisms in 19/24 (79.16?%) and 4/24 (16.67?%) vials, respectively. Seven polymicrobial sepsis models with C. albicans + C. glabrata were also tested. Mycosis vials could detect both yeasts in 7/7 mixed cultures. The aerobic vials from Bactec and BacT/Alert could detect both yeasts in 3/7 and 2/7 mixed cultures, respectively. Bactec Plus Aerobic/F had a shorter TTD compared to BacT/Alert FA and Bactec Plus Anaerobic/F vials (p?<?0.0001 and p?<?0.01, respectively). The present study shows that the Bactec and BacT/Alert systems have different characteristics in the detection of yeasts and bacteria with polymicrobial sepsis.     

HIV-2 A-subtype gp125c₂-v₃-c₃ mutations and their association with CCR5 and CXCR4 tropism

The early events of the HIV replication cycle involve the interaction between viral envelope glycoproteins and their cellular CD4-chemokine (CCR5/CXCR4) receptor complex. In this study, for the first time, the HIV-2 A-subtype gp125_C2-V3-C3 mutations and their tropism association were characterized by analyzing 149 HIV-2 sequences from the Los Alamos database. The analysis has strengthened the importance of C2-V3-C3 region as a determinant factor for co-receptor selection. Moreover, statistically significant correlations were observed between C2-V3-C3 mutations, and several correlated mutations were associated with CXCR4 and CCR5 co-receptor usage. A dendrogram showed two distinct clusters, with numerous associated mutations grouped, thus dividing CCR5- and CXCR4-tropic viruses. Fourteen X4-tropic virus mutations, all in V3 and C3 domains and forming highly significant subclusters, were found. Finally, R5 associations, two strong subclusters were observed, grouping several C2-V3-C3 mutated positions. These data indicate the possible contribution of C2-V3-C3 mutational patterns in regulating HIV-2 tropism.     

3-T MRI of the biliary tract variations

Purpose

The gallbladder and the biliary tract are structures in close connection with the adjacent organs and may show a number of variations and anomalies. It is therefore important for surgical purposes to know their anatomy and variations in detail. Various methods are used in the imaging of the variations of the biliary tract and its pathologies, including ultrasonography, computed tomography; direct cholangiographic methods like endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, intravenous cholangiography and T-tube cholangiography, as well as indirect methods like magnetic resonance cholangiopancreatography (MRCP) or cholescintigraphy. The aim of this study is to investigate the frequency of the anatomic variations of the biliary tract using 3-T MRCP and to compare the findings with the data in the literature.

Materials and methods

For the purposes of this study, patients who underwent MRCP at our hospital (Dicle University Hospital) between November 2009 and February 2012 were investigated retrospectively. A total of 590 patients (between 6 and 88 years of age; mean age: 51 ± 9 years) were included in the study. The MRCP imaging was carried out with an magnetic resonance imaging (MRI) device supplied with 3-T magnetic power and by obtaining T2-weighted images through the single-shot fast spin echo technique using the standard body coil. The axial and coronal source images and the reformatted images were evaluated together in terms of the possible anatomic variations.

Results

Among the 590 patients included in the study, of 233 (39.5 %) showed anatomic variations at different levels in the intra- and extrahepatic biliary tracts. Among these variations, a right posterior hepatic duct insertion to the left hepatic duct at the level of the bifurcation has been observed in 71 patients (12.1 %), trifurcation was observed in 30 patients (5.1 %) and insertion into the main hepatic duct at the proximal aspect of the cystic duct was observed in 18 patients (3.1 %). At the level of the cystic duct, medial insertion of the cystic duct was viewed in 58 patients (9.8 %), distal medial insertion was seen in 40 patients (6.8 %), a short cystic duct was detected in 10 patients (1.7 %), pancreatobiliary junction anomaly was viewed in two patients (0.4 %) and duplicate anatomic variations have been observed in 42 patients (7.2 %).

Conclusion

MRCP studies conducted using 3-T MRI devices may reveal similar or greater numbers of variations when compared to the existing MRCP studies in the literature. 3-T MRI shows a couple of variations. Pointing out these anatomical variations before the surgical intervention may prevent possible iatrogenic traumas. Donors with unsuitable variations for liver transplant may be spotted out at an early phase through the MRCP and certain operations with a high morbidity rate may thus be avoided.