A missense variant in desmoglein-2 predisposes to dilated cardiomyopathy

Familial Dilated Cardiomyopathy (FDCM) is caused by mutations in genes encoding myocardial force transduction proteins. Desmoglein-2 (DSG2) and Desmocollin-2 (DSC2) provide cellular adhesion and force transduction by cell-to-cell anchorage. To test whether perturbations of DSG2 or DSC2 exhibit a pathogenic impact on DCM pathogenesis, we sequenced both genes in 73 patients with FDCM and assessed prevalence of missense variations in matched control cohorts. We detected two missense variations in DSG2 (V55M and V919G) which were absent in 360 control alleles. Surprisingly, both variants were previously reported in patients with arrhythmogenic right ventricular cardiomyopathy. Yet, in the present study only the DSG2-V55M variant showed segregation with DCM in a family pedigree. Subsequent, analysis of 538 patients with idiopathic DCM and 617 consecutive control individuals resulted in identification of thirteen DSG2-V55M carriers with DCM, whereas only three control subjects harbored the variant. DSG2 immunostaining revealed pale structures of the intercalated disc in myocardium of one unique homozygous DSG2-V55M carrier. Furthermore, myocardial desmosomal structures were significantly shortened when compared to DCM myocardium negative for DSG2-V55M. Thus, our study identified the DSG2-V55M polymorphism as a novel risk variant for DCM associated with shortened desmosomes of the cardiac intercalated disc.     

Mini-open versus closed reduction in titanium elastic nailing of paediatric femoral shaft fractures: a comparative study

The purpose of this study is to compare retrospectively intraoperative fluoroscopy time and clinical-radiological results in pediatric femoral shaft fractures treated with titanium elastic nailing (TEN), with a mini-open "blind-hand" technique versus closed reduction. The study included 87 children (18 girls and 69 boys) who underwent surgical treatment with TEN for femoral shaft fractures. Patients were divided into two groups. Group 1 included 42 patients (mean age : 83 +/- 2.7 years) treated with a mini-open "blind-ha nd" technique (a 2-3 cm lateral incision at the level of the fracture ; reduction achieved with one or two fingers, without visualization of the fracture). Group 2 consisted of 45 patients (mean age: 8.8 +/- 2.6 years) treated with a closed reduction technique. Duration of surgery and intraoperative fluoroscopy time were recorded in both groups. Clinical and radiologic results were assessed using the TEN scoring system after mean follow-up periods of 213 +/- 5.8 months and 193 +/- 5.6 months in group 1 and group 2, respectively. Mean duration of surgery was 31.7 +/- 7.6 and 52.1 +/- 14.4 minutes, and mean fluoroscopy time 32.9 +/- 22.1 and 75.1 +/- 31.5 seconds in group 1 and group 2, respectively. Both surgical and fluoroscopy time were significantly longer in group 2 (p < 0.001). There was no significant difference between the two groups in terms of clinical and radiological results. All fractures healed with solid union, and there was no complication that was expected to cause permanent disability. Although successful clinical and radiological results were obtained with both techniques, duration of surgery and intraoperative fluoroscopy time were significantly higher in the closed reduction group 2. We suggest the "blind-hand" technique as an alternative to closed reduction to prevent extensive intraoperative radiation exposure and to decrease the length of the surgical procedure.     

Clinical presentation,management, screening and surveillance for colorectal cancer during the COVID-19 pandemic

Management of colorectal cancer (CRC) was severely affected by the changes implemented during the pandemic, and this resulted in delayed elective presentation, increased emergency presentation, reduced screening and delayed definitive therapy. This review was conducted to analyze the impact of the coronavirus disease 2019 (COVID-19) pandemic on management of CRC and to identify the changes made in order to adapt to the pandemic. We performed a literature search in PubMed, Medline, Index Medicus, EMBASE, SCOPUS, Reference Citation Analysis (https://www.referencecitationanalysis.com/) and Google Scholar using the following keywords in various combinations: Colorectal cancer, elective surgery, emergency surgery, stage upgrading, screening, surveillance and the COVID-19 pandemic. Only studies published in English were included. To curtail the spread of COVID-19 infection, there were modifications made in the management of CRC. Screening was limited to high risk individuals, and the screening tests of choice during the pandemic were fecal occult blood test, fecal immunochemical test and stool DNA testing. The use of capsule colonoscopy and open access colonoscopy was also encouraged. Blood-based tests like serum methylated septin 9 were also encouraged for screening of CRC during the pandemic. The presentation of CRC was also affected by the pandemic with more patients presenting with emergencies like obstruction and perforation. Stage migration was also observed during the pandemic with more patients presenting with more advanced tumors. The operative therapy of CRC was altered by the pandemic as more emergencies surgeries were done, which may require exteriorization by stoma. This was to reduce the morbidity associated with anastomosis and encourage early discharge from the hospital. There was also an initial reduction in laparoscopic surgical procedures due to the fear of aerosols and COVID-19 infection. As we gradually come out of the pandemic, we should remember the lessons learned and continue to apply them even after the pandemic passes.     

The Expression of GDF-15 in the Human Vitreous in the Presence of Retinal Pathologies with an Inflammatory Component

Purpose: The presence of growth differentiation factor-15 (GDF-15), a protein implicated in the regulation of the inflammatory response, was investigated in the vitreous of patients with vitreoretinal disorders.

Methods: Vitreous and plasma samples were collected from patients with idiopathic epiretinal membrane (IERM), macular hole (MH), rhegmatogenous retinal detachment (RRD), nucleus drop (ND), or proliferative diabetic retinopathy (PDR). GDF-15 concentrations were measured using ELISA.

Results: The vitreous levels of GDF-15 were higher in ND (5) and PDR (14) patients (1494?±?243 and 904?±?138?pg/mL, respectively) than RRD (3), MH (3), and IERM (8) patients (302?±?160, 288?±?24, and 254?±?91?pg/mL, respectively). The vitreous levels of GDF-15 were significantly higher in patients with inflammatory vitreoretinal disorders (p?Conclusions: This is the first report showing that GDF-15 appears to be expressed in the vitreous, and that its expression is significantly higher in the presence of a vitreoretinal disorder in which there is an inflammatory component.     

Reevaluation of an Old Electrocardiographic Criterion for Coronary Disease: TV1 > TV6

Background: Two different studies were conducted to evaluate the value of T wave in V₁ taller than T wave in V₆ (TV₁ > TV₆) pattern as an indicator of coronary artery disease. Method: In the first study 5,300 resting ECGs were examined and the criterion was found in 283 patients. All of these patients were examined with echocardiography. In the second study, ECG tracings and coronary angiograms of another 500 patients were evaluated. Results: In the first study, in 59 of 283 patients left ventricular hypertrophy was detected and these patients were excluded from the study. There were ST segment-T wave changes and/or Q wave on ECG suggesting coronary ischemia or myocardial infarction in 160 of the 224 patients. TV₁, > TV₆ criterion was the sole finding in 64 of the 224 patients. All of the 224 patients underwent coronary angiography and coronary artery disease was detected in 185 patients; 134 of the 160 patients (83.3%) and 51 of 64 patients (80%) had one-vessel or multivessel disease. There was no significant difference among the groups regarding coronary artery disease. Left anterior descending artery was involved in all of the 185 patients. In the second study, 408 patients were found to have coronary disease involvement and 92 patients showed normal or insignificant coronary disease. Sixty-six of the 408 patients with coronary disease and four of 92 patients were found to have the TV₁ > TV₆ pattern. Sensitivity of the criterion was 16.1%, specificity was 95.6%, and accuracy was 94.2%. Conclusions: According to these results, it is concluded that TV₁ > TV₆ with or without other ECG findings is a good criterion suggesting coronary artery disease, especially left anterior descending artery involvement in patients without left ventricular hypertrophy. A.N.E. 1999;4(4):397–400