A novel intermediate coronary artery stenosis severity method: Fluoroscopy-Assisted Measurement of Coronary Volume Ratio (The FLAME FFR Trial).

OBJECTIVE: The fluoroscopy-assisted coronary volume measurement (FLASH) algorithm, based on contrast passage time and vessel size, is a simple and non-invasive method of assessing coronary blood volume. The present study evaluated the diagnostic performance of FLASH flow ratio-derived fractional flow reserve (FFRFLAME) compared to wire-based FFR (FFRWB). PATIENTS AND METHODS: FFRFLAME was defined as the ratio of FLASH at baseline to maximal hyperemia. Forty-eight patients with one intermediate coronary lesion (30-70% by angiographic visual estimation) were enrolled in this cross-sectional study. FFRFLAME and FFRWB measurements were collected in each patient. Intravenous administration of adenosine was used to achieve maximal hyperemia. The Pearson correlation coefficient and receiver operating characteristic analysis were performed to determine the predictive accuracy of FFRFLAME. RESULTS: The average age of the patients was 58 years, and 43% (21 of 48) were female. The predominant vessel assessed was the left anterior descending artery system (87.5%). The mean FFRWB was 0.91 ± 0.05 at baseline and 0.83 ± 0.07 at the hyperaemic level, with 27% (13 of 48) of patients having an FFRWB of ≤0.80. For each patient, the mean FFRFLAME was 0.668 ± 0.17. The mean FFRFLAME was 0.85 ± 0.16 for patients having an FFRWB of ≤0.80. A strong relationship existed between FFRFLAME and FFRWB (Pearson's r = - 0.765 p<0.001). The optimal cutoff value of the functional significance of coronary artery stenosis for FFRFLAME was determined to be > 0.84 (AUC: 0.899, 84% sensitivity and 97% specificity) when the FFRWB cutoff value for significant lesions was ≤ 0.80. CONCLUSIONS: FFRFLAME, applied to coronary angiography without the need for an invasive pressure wire, can be a beneficial index for appropriate lesion selection in coronary artery diseases.

Predictors for extubation failure in COVID-19 patients using a machine learning approach.

INTRODUCTION: Determining the optimal timing for extubation can be challenging in the intensive care. In this study, we aim to identify predictors for extubation failure in critically ill patients with COVID-19. METHODS: We used highly granular data from 3464 adult critically ill COVID patients in the multicenter Dutch Data Warehouse, including demographics, clinical observations, medications, fluid balance, laboratory values, vital signs, and data from life support devices. All intubated patients with at least one extubation attempt were eligible for analysis. Transferred patients, patients admitted for less than 24 h, and patients still admitted at the time of data extraction were excluded. Potential predictors were selected by a team of intensive care physicians. The primary and secondary outcomes were extubation without reintubation or death within the next 7 days and within 48 h, respectively. We trained and validated multiple machine learning algorithms using fivefold nested cross-validation. Predictor importance was estimated using Shapley additive explanations, while cutoff values for the relative probability of failed extubation were estimated through partial dependence plots. RESULTS: A total of 883 patients were included in the model derivation. The reintubation rate was 13.4% within 48 h and 18.9% at day 7, with a mortality rate of 0.6% and 1.0% respectively. The grandient-boost model performed best (area under the curve of 0.70) and was used to calculate predictor importance. Ventilatory characteristics and settings were the most important predictors. More specifically, a controlled mode duration longer than 4 days, a last fraction of inspired oxygen higher than 35%, a mean tidal volume per kg ideal body weight above 8 ml/kg in the day before extubation, and a shorter duration in assisted mode (< 2 days) compared to their median values. Additionally, a higher C-reactive protein and leukocyte count, a lower thrombocyte count, a lower Glasgow coma scale and a lower body mass index compared to their medians were associated with extubation failure. CONCLUSION: The most important predictors for extubation failure in critically ill COVID-19 patients include ventilatory settings, inflammatory parameters, neurological status, and body mass index. These predictors should therefore be routinely captured in electronic health records.

MicroRNAs expression profiles as biomarkers and therapeutic tools in Turkish patients with chronic myeloid leukemia.

AIM: In 95 % of Chronic myeloid leukemia (CML) patients, chromosomal translocation resulting in the formation of the Philadelphia (Ph) chromosome (t:9;22) is observed, which in turn leads to the formation of the BCR-ABL fusion gene. MicroRNAs (miRNAs) are a group of small and non-coding RNAs modulating gene expression via binding to the target mRNAs. We aimed to characterize the expression profiles of various miRNAs in different stages of Ph(+) CML patients. METHODS: This case-controlled study was conducted in 75 CML patients and 25 healthy controls. The subjects were categorized into 4 groups; newly diagnosed patients, treatment-response patients, treatment-failure patients, and healthy controls. Expressions of miRNAs was analyzed by RT-PCR. RESULTS: miR-150 expression was downregulated in the treatment failure patients compared to the control group (p = 0.003212) while miRNA 148b expression up-regulated in the treatment failure patients than the control group (p = 0.038016). miR-10a expression was up-regulated in newly diagnosed and treatment response patients compared to control group (p = 0.003934, p = 0.000292, respectively). It was found that miR-10a expression increased 11.17- fold in newly diagnosed patients and 9.82-fold in treatment response patients than in the control group. CONCLUSION: Our data suggest that expression profiles of miR-10a, miR-150, and miRNA 148b were correlated as biomarker and therapeutic tool in Turkish patients with CML (Tab. 2, Fig. 1, Ref. 30).

Evaluation of sexual functions and marital adjustment of pregnant women in Turkey.

The aim of this study was to evaluate pregnant women's sexual function and marital adjustment. The sample of the study included 298 women, and it was evaluated using Golombok Rust Inventory of Sexual Satisfaction (GRISS) Scale and Marital Adjustment Scale. The most important reasons for decreasing the frequency of sexual intercourse included the fear of harming the fetus during intercourse (62.1%), fear of having miscarriage (47.8%) and decreased sexual desire (34.7%). It was found that women with sexual dysfunction had a significantly lower educational level, were living with three or more people in their home, were multiparious, had an unplanned pregnancy, reported pain during sexual intercourse and felt that their sexual life was very affected during pregnancy. The findings of the study showed that women had ⩾5 points for GRISS for the subscales as follows: infrequency (47.3%), non-communication (57.4%), dissatisfaction (15.4%), avoidance (6.4%), non-sensuality (19.1%), vaginismus (28.9%), anorgasmia (29.9%) and sexual dysfunction (17.4%). In conclusion, women who were living with three or more people at home, had lower income level, were smoking and had an unplanned pregnancy scored under 43.5 of MAS. It was found negative and there was a medium correlation between MAS score and total GRISS score.

Usage of whey protein may cause liver damage via inflammatory and apoptotic responses.

The purpose of this study was to investigate the long- and short-term inflammatory and apoptotic effects of whey protein on the livers of non-exercising rats. Thirty rats were divided into three groups namely (1) control group, (2) short-term whey (WS) protein diet (252 g/kg for 5 days), and (3) long-term whey (WL) protein diet (252 g/kg for 4 weeks). Interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor α (TNF-α), and cytokeratin 18 (CK-18-M30) were assessed using enzyme-linked immunosorbent assay and immunohistochemical methods. Apoptosis was evaluated using the terminal transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method. Hepatotoxicity was evaluated by quantitation of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Based on the biochemical levels and immunohistochemical results, the highest level of IL-1ß was identified in the WL group (p < 0.01). The IL-6 and TNF-α results were slightly lower in the WS group than in the control group and were highest in the WL group (p < 0.01). The CK-18-M30 and TUNEL results were highest in the WS group and exhibited medium intensity in the WL group (p < 0.01). AST results were statistically significant for all groups, while our ALT groups were particularly significant between the WL and control groups (p < 0.01). The results showed that when whey protein is used in an uninformed manner and without exercising, adverse effects on the liver may occur by increasing the apoptotic signal in the short term and increasing inflammatory markers and hepatotoxicity in the long term.

Prognostic factors in elderly patients with advanced non-small cell lung cancer treated with first-line cisplatin-based chemotherapy: a retrospective analysis of single institution.

PURPOSE: Non-small cell lung cancer (NSCLC) makes up 80-85% of all lung cancers cases. Lung cancer in older individuals is frequently undertreated. Patients eligible for cisplatin- based chemotherapy should be selected carefully. The aim of this retrospective single-center study was to evaluate prognostic factors for overall survival (OS) in elderly (≥65 years) patients with advanced NSCLC who received first-line cisplatin-based chemotherapy. METHODS: We retrospectively reviewed 110 elderly patients with locally advanced or metastatic NSCLC who had been administered cisplatin-based first-line chemotherapy between December 2004 and November 2011. Seventeen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. RESULTS: Among the 17 variables of univariate analysis, 4 were identified to have prognostic significance for OS: comorbidities (p<0.001), Eastern Cooperative Oncology Group (ECOG) performance status (PS) (p=0.02), first-line chemotherapy cycles (p<0.001) and serum albumin level (p=0.04). Multivariate analysis showed that only ECOG PS (p=0.01) was independent prognostic factor for OS. CONCLUSION: PS was important prognostic factor in elderly patients with advanced NSCLC. The findings of this study may facilitate pretreatment prediction of OS and therefore can be used for selecting the most appropriate treatment for elderly patients.

Prognostic value of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with advanced non-small cell lung cancer: single center experience.

PURPOSE: The purpose of this retrospective single-center study was to evaluate the prognostic implication on overall survival (OS) of the F-18 FDG PET scan in locally advanced or metastatic non small cell lung cancer (NSCLC) patients. METHODS: We retrospectively reviewed 120 locally advanced or metastatic NSCLC patients (December 2004-November 2011) treated/followed at the Dicle University, School of Medicine, Department of Medical Oncology. SUVmax and other potential prognostic variables (n=18) were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors for OS. RESULTS: Among 18 variables of univariate analysis, 6 were identified to bear prognostic significance: sex (p=0.01), performance status (PS) (p =0.03), stage (p=0.04), bone metastases (p=0.002), serum albumin (p=0.01) and blood glucose level (p=0.03). Multivariate analysis showed that PS, bone metastases and serum albumin level were independent prognostic factors for OS (p=0.01, p=0.004, p=0.003, respectively). CONCLUSION: PS, serum albumin levels and bone metastases were independent prognostic factors, while FDG uptake of the primary lesion was not associated with prognosis of OS in locally advanced or metastatic NSCLC patients.

Phase II study of the combination of pegylated liposomal doxorubicin and topotecan in platinum-resistant ovarian cancer.

The combination of liposomal doxorubicin and topotecan was evaluated in a phase II study in patients with platinum-resistant ovarian cancer. Twenty-seven patients received liposomal doxorubicin (30 mg/m(2)) infused at day 1, followed by topotecan (1 mg/m(2)) infusion daily for 5 days. Cycles were repeated every 21 days. This combination regimen showed an overall response rate of 28%. Median time to progression was 30 weeks, with a median overall survival of 40 weeks. Grade 3/4 neutropenia was shown in 70% of patients and grade 3/4 thrombopenia in 41% of patients. Neutropenic fever was reported in 11% of patients. After reviewing the first 12 patients, the internal review board decided to administer topotecan at a dose of 0.75 mg/m(2) and liposomal doxorubicin at 40 mg/m(2) for the remainder of the study. However, this adjustment did not lead to reduction in bone marrow toxicity nor to an improvement in dose intensity. Palmar-plantar erythrodysesthesia and mucositis were more reported in the second cohort but usually mild. The combination of liposomal doxorubicin and topotecan demonstrates favorable response data in platinum-resistant ovarian cancer. However, substantial bone marrow toxicity limits further clinical use.