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Keratoconus is a potentially blinding condition that slowly deforms the cornea in young people. Despite the increasing prevalence of keratoconus, the exact aetiology of the condition is unknown. This first systematic review examines the evidence of eye rubbing and its association with keratoconus and presents the findings of the meta-analysis.

Two independent reviewers searched the electronic databases for all potential articles published from 1st of January 1900 to 31st of July 2020 on eye rubbing and keratoconus. The researchers assessed the methodological quality of the studies using the Newcastle-Ottawa scale for observational studies. The assessment for statistical heterogeneity was estimated using chi-square and I-square (I
) tests. A p value of < 0.05 was considered as statistically significant and I
 < 30% as homogenous. Begg funnel plot was used to interpret the asymmetry or small study effects.

Eight case-control studies were included in this systematic review. Fisogatinib order Two studies assessed eyeal methodological quality. Additionally, the cause-effect temporal relationship cannot be determined. Further studies are needed to address this intricate relationship of eye rubbing and its induction, ongoing progression, and severity of keratoconus.One of the major hurdles for the advancement of cancer immunotherapy is lack of robust, accessible experimental models. We aimed to produce an ex-vivo organ culture (EVOC) model of immunotherapy for non-small cell lung cancer (NSCLC). Freshly resected early stage tumors were collected from the operating room, fragmented to clusters  less then  450 µm and cultured with fetal calf serum and human autologous serum. The resulting EVOC includes cancer epithelial cells within tumor tissue clusters and immune cells. Original tissue features are reflected in the EVOCs. The response to immune checkpoint inhibitors (ICI) was assessed by IFNγ gene induction. Interestingly, IFNγ EVOC induction was numerically higher when anti-CTLA4 was added to anti-PD-L1 treatment, supporting the notion that anti-CTLA4 impacts cancer partly through tumor-resident immune cells. In parallel, immunohistochemistry (IHC) for key immune-related proteins was performed on the formalin-fixed paraffin embedded (FFPE) corresponding tumors. EVOC IFNγ induction by ICI correlated with basal non-induced IFNγ, CD8, CD4 and FOXP3 mRNA levels within EVOCs and with tumor-FFPE-IHC for CD8 and granzyme B. A weaker correlation was seen with tumor-FFPE-IHC for CD3, CD4, CD68, FOXP3 and tumor-PD-L1. Tertiary lymphoid structure density was also correlated with the ICI response. Our study provides novel data about biomarkers that correlate with ICI-induced response of early stage NSCLC. Retention of the microenvironment and minimal addition of exogenous factors suggest this model to reliably represent the original tumor. link2 The cluster-based EVOC model we describe can provide a valuable, yet simple and widely applicable tool for the study of immunotherapy in NSCLC.
Necrotizing fasciitis (NF) is a rapidly progressive inflammatory infection of the fascia, with secondary necrosis of the subcutaneous tissues. The severity of the disease depends on the virulence of the organism and host immunity. Fisogatinib order There is a paucity of reports on the prevalence of NF causing pathogens and management.

Retrospective data of patients treated for NF were collected from two tertiary care hospitals in Central Malaysia between January 2014 and December 2018.

A total of 469 NF patients were identified. More than half of the NF patients were males (n = 278; 59.28%). The highest number of cases was found among age groups between 30 and 79, with mean age of 56.17. The majority of the NF cases (n = 402; 85.72%) were monomicrobial. link3 Streptococcus spp. (n = 89; 18.98%), Pseudomonas aeruginosa (n = 63; 13.44%) and Staphylococcus spp. (n = 61; 13.01%) were identified as the top three microorganisms isolated. Among the 469 NF cases, 173 (36.8%) were amputated or dead while 296 (63.1%) recovered. Proteus spp. (n = 19; 12.93%), Klebsiella pneumoniae (n = 18; 12.24%) and Escherichia coli (n = 14; 9.52%) were associated with all types of amputations. The most common antibiotic prescribed was unasyn (n = 284; 60.56%), followed by clindamycin (n = 56; 11.94%) and ceftazidime (n = 41; 8.74%). A total of 239 (61.8%) recovered while 148 (38.2%) were either amputated or dead when managed with the unasyn, clindamycin or ceftazidime.

This study represents the largest NF cases series in Malaysia highlighting the causative agents and management.
This study represents the largest NF cases series in Malaysia highlighting the causative agents and management.Endothelin-1 contributes to the constrictor response of the coronary arteries in patients with ischemia with normal coronary arteries. There is thus increasing evidence that endothelin-1 plays a role in coronary microvascular dysfunction (CMD). We investigated whether elevated endothelin-1 is associated with CMD in patients with coronary artery disease (CAD). We prospectively studied 49 consecutive CAD patients with 1- or 2-vessel disease (age 71 ± 10 years, 43 males). Myocardial blood flow (MBF) was measured by 15O-water PET/CT at rest and during stress, and the coronary flow reserve (CFR) was calculated by dividing the stress MBF by the rest MBF. A CFR of less than 2.0 in non-obstructive regions was defined as a marker of CMD. Eighteen out of 49 (37%) CAD patients had CMD. Endothelin-1 in patients with CMD was significantly higher than in those without CMD (2.27 ± 0.81 vs. 1.64 ± 0.48 pg/mL, P = 0.001). Accordingly, univariate ROC analysis showed that the continuous endothelin-1 levels significantly discriminated between the presence and absence of CMD (area under the curve = 0.746 [95%CI 0.592-0.899]). The dichotomous treatment of elevated endothelin-1 as 1.961 pg/mL or more yielded the optimal discriminatory capacity, with a sensitivity of 72.2% and a specificity of 71.0%. link2 High endothelin-1 was still a significant predictor of CMD after adjusting for diabetes mellitus (odds ratio = 6.64 [1.75-25.22], P = 0.005). Endothelin-1 is associated with CMD in non-obstructive territories in patients with CAD, suggesting that endothelin-1 is a potential target for treating CMD in CAD patients.Preoperative frailty diminishes the potential for functional recovery after transcatheter aortic valve implantation (TAVI). However, perioperative changes in physical status and their impact on prognosis after TAVI have not previously been reported. Therefore, this study aimed to investigate whether perioperative changes in physical function affect prognosis in patients undergoing TAVI. We retrospectively reviewed 257 patients who underwent TAVI. The Short Physical Performance Battery (SPPB), an objective physical status assessment tool, was evaluated pre- and post-TAVI. Patients were divided into two groups (i) patients whose SPPB score declined in the perioperative period (the decline group) and (ii) patients whose SPPB score did not decline in the perioperative period (the non-decline group). The primary endpoint was unplanned hospitalization owing to heart failure or cardiovascular death following TAVI. The mean follow-up period was 385 ± 151 days, mean age was 83.2 ± 5.8 years, and 67% of the patients were women. Sixteen patients required readmission owing to heart failure, and seven experienced cardiovascular-related death. Kaplan-Meier analysis revealed that the event-free rate was significantly lower in the decline group (log-rank, p = 0.006). Fisogatinib order A stepwise multivariate logistic regression analysis showed that a perioperative change in SPPB was significantly associated with primary endpoints (odds ratio, 1.51; 95% confidence interval, 1.12-2.04). Perioperative change in physical function was an independent risk factor for heart failure, hospitalization, or cardiovascular death following TAVI.Anaerobic threshold (AT) from cardiopulmonary exercise tests (CPX) is the standard for measuring exercise intensity among patients with cardiovascular disease in Japan. However, it remains controversial whether AT represents the safety limit for exercise intensity in patients with cardiovascular disease. The purpose of this study was to investigate cardiac rehabilitation (CR) efficacy and safety with exercise intensities above the AT and at a traditional AT in a randomized trial. The participants included 57 patients who were admitted to the outpatient CR unit with a diagnosis of acute myocardial infarction. The participants were randomly divided as follows 25 patients in the AT group, who performed aerobic exercises with an intensity at the AT; and 32 patients in the "Over AT" group, who performed exercises at an intensity higher than the AT. The following components were measured maximum oxygen uptake (peak VO2), oxygen uptake at the AT (AT VO2), increase in oxygen uptake during exercise (ΔVO2/ΔWR) during tnt rate was associated with changes in isometric knee extension strength.Myocardial perfusion and perfusion reserve are diminished in patients with atrial fibrillation (AF). link2 Phase-contrast (PC) cine magnetic resonance imaging (MRI) of the coronary sinus serves as a non-invasive means of quantifying coronary flow reserve (CFR) without any radioactive tracer. link3 The present study aimed to evaluate the utility of PC cine MRI of the coronary sinus for assessing decreased CFR in patients with AF. We studied 362 patients with known or suspected coronary artery disease (CAD) [age 72 ± 9 years; 267 (74%) male; 90 (25%) had AF] and 20 age- and gender-matched control subjects [age 72 ± 9 years, 14 (70%) male]. link3 Using a 1.5-T MR scanner and cardiac coils, blood flow of the coronary sinus (CBF) was quantified by PC cine MRI. CFR was calculated as CBF during adenosine triphosphate infusion divided by CBF at rest. CFR was significantly lower in patients with AF than in those without AF among all patients (n = 362) (2.45 ± 0.42 vs. 2.71 ± 0.58, p  less then  0.001), in patients with known CAD (n = 155) (2.40 ± 0.46 vs. 2.72 ± 0.58, p = 0.002), and in those with suspected CAD (n = 207) (2.49 ± 0.40 vs. 2.72 ± 0.59, p = 0.007). Significant differences in CFR were found between controls and patients without AF (3.12 ± 0.52 vs. 2.71 ± 0.58, p  less then  0.001). AF was independently associated with CFR in both known CAD patients [β = - 0.248, 95% confidence interval (CI) - 0.561 to - 0.119, p = 0.003) and suspected CAD patients (β =  - 0.154, 95% CI - 0.353 to - 0.034, p = 0.018). The presence of AF was related to impaired CFR in both known and suspected CAD patients. PC cine MRI of the coronary sinus can be useful for detecting impaired CFR in patients with AF.The aim of this study was to determine factors associated with physical fitness (PF) in children who underwent surgery for congenital heart disease (CHD). Sixty-six children (7-14 years) who underwent surgery for ventricular septal defect (n = 19), transposition of great arteries (n = 22), coarctation of aorta (n = 10), and tetralogy of Fallot (n = 15) were included. All children performed PF tests cardiorespiratory fitness, upper- and lower-limb muscle strength, speed, balance, and flexibility. Cardiac evaluation was done via echocardiography and cardiopulmonary exercise test. Factors related to child's characteristics, child's lifestyle, physical activity motivators/barriers, and parental factors were assessed. Linear regression analyses were conducted. The results showed no significant differences in physical activity (PA) level by CHD type. Boys had better cardiorespiratory fitness (difference = 1.86 ml/kg/min [0.51;3.22]) and were more physically active (difference = 19.40 min/day [8.14;30.66]), while girls had better flexibility (difference = - 3.
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