Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations.

Organ fibrosis is a shared endpoint of many diseases, yet underlying mechanisms are not well understood. Several pathways governed by the primary cilium, a sensory antenna present on most vertebrate cells, have been linked with fibrosis. Ciliopathies usually start early in life and represent a considerable disease burden. We performed massively parallel sequencing by using cohorts of genetically unsolved individuals with unexplained liver and kidney failure and correlated this with clinical, imaging, and histopathological analyses. Mechanistic studies were conducted with a vertebrate model and primary cells. We detected bi-allelic deleterious variants in TULP3, encoding a critical adaptor protein for ciliary trafficking, in a total of 15 mostly adult individuals, originating from eight unrelated families, with progressive degenerative liver fibrosis, fibrocystic kidney disease, and hypertrophic cardiomyopathy with atypical fibrotic patterns on histopathology. We recapitulated the human phenotype in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals. Further, we show interaction between TULP3 and the nuclear deacetylase SIRT1, with roles in DNA damage repair and fibrosis, and report increased DNA damage ex vivo. Transcriptomic studies demonstrated upregulation of profibrotic pathways with gene clusters for hypertrophic cardiomyopathy and WNT and TGF-ß signaling. These findings identify variants in TULP3 as a monogenic cause for progressive degenerative disease of major organs in which affected individuals benefit from early detection and improved clinical management. Elucidation of mechanisms crucial for DNA damage repair and tissue maintenance will guide novel therapeutic avenues for this and similar genetic and non-genomic diseases.

Metabolomic prediction of severe maternal and newborn complications in preeclampsia.

INTRODUCTION: Preeclampsia (PreE) remains a major source of maternal and newborn complications. Prenatal prediction of these complications could significantly improve pregnancy management. OBJECTIVES: Using metabolomic analysis we investigated the prenatal prediction of maternal and newborn complications in early and late PreE and investigated the pathogenesis of such complications. METHODS: Serum samples from 76 cases of PreE (36 early-onset and 40 late-onset), and 40 unaffected controls were collected. Direct Injection Liquid Chromatography-Mass Spectrometry combined with Nuclear Magnetic Resonance (NMR) spectroscopy was performed. Logistic regression analysis was used to generate models for prediction of adverse maternal and neonatal outcomes in patients with PreE. Metabolite set enrichment analysis (MSEA) was used to identify the most dysregulated metabolites and pathways in PreE. RESULTS: Forty-three metabolites were significantly altered (p < 0.05) in PreE cases with maternal complications and 162 metabolites were altered in PreE cases with newborn adverse outcomes. The top metabolite prediction model achieved an area under the receiver operating characteristic curve (AUC) = 0.806 (0.660-0.952) for predicting adverse maternal outcomes in early-onset PreE, while the AUC for late-onset PreE was 0.843 (0.712-0.974). For the prediction of adverse newborn outcomes, regression models achieved an AUC = 0.828 (0.674-0.982) in early-onset PreE and 0.911 (0.828-0.994) in late-onset PreE. Profound alterations of lipid metabolism were associated with adverse outcomes. CONCLUSION: Prenatal metabolomic markers achieved robust prediction, superior to conventional markers for the prediction of adverse maternal and newborn outcomes in patients with PreE. We report for the first-time the prediction and metabolomic basis of adverse maternal and newborn outcomes in patients with PreE.

Safety of magnetic resonance imaging in patients with cardiac implantable electronic devices and abandoned or epicardial leads: a systematic review and meta-analysis.

AIMS: Persistent reluctance to perform magnetic resonance imaging (MRI) in patients with abandoned and/or epicardial leads of cardiac implantable electronic devices is related to in vitro studies reporting tip heating. While there is a plethora of data on the safety of MRI in conditional and non-conditional implantable devices, there is a clear lack of safety data in patients with abandoned and/or epicardial leads. METHODS AND RESULTS: Relevant literature was identified in Medline and CINAHL using the key terms 'magnetic resonance imaging' AND 'abandoned leads' OR 'epicardial leads'. Secondary literature and cross-references were supplemented. For reporting guidance, the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 was used. International Prospective Register of Systematic Reviews (PROSPERO) registration number 465530. Twenty-one publications with a total of 656 patients with 854 abandoned and/or epicardial leads and 929 MRI scans of different anatomical regions were included. No scan-related major adverse cardiac event was documented, although the possibility of under-reporting of critical events in the literature should be considered. Furthermore, no severe device dysfunction or severe arrhythmia was reported. Mainly transient lead parameter changes were observed in 2.8% in the subgroup of patients with functional epicardial leads. As a possible correlate of myocardial affection, subjective sensations occurred mainly in the subgroup with abandoned epicardial leads (4.0%), but no change in myocardial biomarkers was observed. CONCLUSION: Existing publications did not report any relevant adverse events for MRI in patients with abandoned and/or epicardial leads if performed according to strict safety guidelines. However, a more rigorous risk-benefit calculation should be made for patients with epicardial leads.

Efficacy and safety of bevacizumab in patients with low-grade serous ovarian cancer.

Aim: To investigate the efficacy and safety of bevacizumab in patients with recurrent low-grade serous ovarian carcinoma. Materials & methods: The data of patients who received at least two cycles of bevacizumab in combination with chemotherapy were retrospectively recorded. Results: The median age of 51 patients was 56 (range: 33-75) years. The complete response rate was 10.4% and the partial response rate was 43.7%. The objective response rate was 54.1%. Median progression-free survival was 15.9 months (95% CI: 9.1-22.6) and median overall survival was 42.5 months (95% CI: 37.2-47.8). Conclusion: Bevacizumab with chemotherapy is an effective option for treating recurrent ovarian low-grade serous carcinoma.

Myocardial Fibrosis at Cardiac MRI Helps Predict Adverse Clinical Outcome in Patients with Mitral Valve Prolapse.

Background Patients with mitral valve prolapse (MVP) may develop adverse outcomes even in the absence of mitral regurgitation or left ventricular (LV) dysfunction. Purpose To investigate the prognostic value of mitral annulus disjunction (MAD) and myocardial fibrosis at late gadolinium enhancement (LGE) cardiac MRI in patients with MVP without moderate-to-severe mitral regurgitation or LV dysfunction. Materials and Methods In this longitudinal retrospective study, 118 144 cardiac MRI studies were evaluated between October 2007 and June 2020 at 15 European tertiary medical centers. Follow-up was from the date of cardiac MRI examination to June 2020; the minimum and maximum follow-up intervals were 6 months and 156 months, respectively. Patients were excluded if at least one of the following conditions was present: cardiomyopathy, LV ejection fraction less than 40%, ischemic heart disease, congenital heart disease, inflammatory heart disease, moderate or worse mitral regurgitation, participation in competitive sport, or electrocardiogram suggestive of channelopathies. In the remainder, cardiac MRI studies were reanalyzed, and patients were included if they were aged 18 years or older, MVP was diagnosed at cardiac MRI, and clinical information and electrocardiogram monitoring were available within 3 months from cardiac MRI examination. The end point was a composite of adverse outcomes: sustained ventricular tachycardia (VT), sudden cardiac death (SCD), or unexplained syncope. Multivariable Cox regression analysis was performed. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 women) were included. Over a median follow-up of 3.3 years, 18 patients (4%) reached the study end point. LGE presence (hazard ratio, 4.2 [95% CI: 1.5, 11.9]; P = .006) and extent (hazard ratio, 1.2 per 1% increase [95% CI: 1.1, 1.4]; P = .006), but not MAD presence (P = .89), were associated with clinical outcome. LGE presence had incremental prognostic value over MVP severity and sustained VT and aborted SCD at baseline (area under the receiver operating characteristic curve, 0.70 vs 0.62; P = .03). Conclusion In contrast to mitral annulus disjunction, myocardial fibrosis determined according to late gadolinium enhancement at cardiac MRI was associated with adverse outcome in patients with mitral valve prolapse without moderate-to-severe mitral regurgitation or left ventricular dysfunction. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gerber in this issue.

Non-targeted LC-MS/MS metabolomic profiling of human plasma uncovers a novel Mediterranean diet biomarker panel.

INTRODUCTION: Consumption of a Mediterranean diet (MD) has established health benefits, and the identification of novel biomarkers could enable objective monitoring of dietary pattern adherence. OBJECTIVES: The present investigation performed untargeted metabolomics on blood plasma from a controlled study of MD adherence, to identify novel blood-based metabolite biomarkers associated with the MD pattern, and to build a logistic regression model that could be used to characterise MD adherence. METHODS: A hundred and thirty-five plasma samples from n = 58 patients collected at different time points were available. Using a 14-point scale MD Score (MDS) subjects were divided into 'high' or 'low' MDS adherence groups and liquid chromatography-mass spectrometry (LC-MS/MS) was applied for analysis. RESULTS: The strongest association with MDS was pectenotoxin 2 seco acid (r = 0.53; ROC = 0.78), a non-toxic marine xenobiotic metabolite. Several lipids were useful biomarkers including eicosapentaenoic acid, the structurally related lysophospholipid (20:5(5Z,8Z,11Z,14Z,17Z)/0:0), a phosphatidylcholine (P-18:1(9Z)/16:0) and also xi-8-hydroxyhexadecanedioic acid. Two metabolites negatively correlated with MDS, these were the monoacylglycerides (0:0/16:1(9Z)/0:0) and (0:0/20:3(5Z,8Z,11Z)/0:0). By stepwise elimination we selected a panel of 3 highly discriminatory metabolites and developed a linear regression model which identified 'high MDS' individuals with high sensitivity and specificity [AUC (95% CI) 0.83 (0.76-0.97)]. CONCLUSION: Our study highlights the utility of metabolomics as an approach for developing novel panels of dietary biomarkers. Quantitative profiling of these metabolites is required to validate their utility for evaluating dietary adherence.

Fetal effects of mild maternal COVID-19 infection: metabolomic profiling of cord blood.

INTRODUCTION: The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized. OBJECTIVES: Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection. METHODS: Cord blood plasma samples from 23 mild COVID-19 cases (mother infected/newborn negative) and 23 gestational age-matched controls were analyzed using nuclear magnetic spectroscopy and liquid chromatography coupled with mass spectrometry. Metabolite set enrichment analysis (MSEA) was used to evaluate altered biochemical pathways due to COVID-19 intrauterine exposure. Logistic regression models were developed using metabolites to predict intrauterine exposure. RESULTS: Significant concentration differences between groups (p-value < 0.05) were observed in 19 metabolites. Elevated levels of glucocorticoids, pyruvate, lactate, purine metabolites, phenylalanine, and branched-chain amino acids of valine and isoleucine were discovered in cases while ceramide subclasses were decreased. The top metabolite model including cortisol and ceramide (d18:1/23:0) achieved an Area under the Receiver Operating Characteristics curve (95% CI) = 0.841 (0.725-0.957) for detecting fetal exposure to maternal COVID-19 infection. MSEA highlighted steroidogenesis, pyruvate metabolism, gluconeogenesis, and the Warburg effect as the major perturbed metabolic pathways (p-value < 0.05). These changes indicate fetal increased oxidative metabolism, hyperinsulinemia, and inflammatory response. CONCLUSION: We present fetal biochemical changes related to intrauterine inflammation and altered energy metabolism in cases of mild maternal COVID-19 infection despite the absence of viral infection. Elucidation of the long-term consequences of these findings is imperative considering the large number of exposures in the population.

Cell-free DNA in maternal blood and artificial intelligence: accurate prenatal detection of fetal congenital heart defects.

BACKGROUND: DNA cytosine nucleotide methylation (epigenomics and epigenetics) is an important mechanism for controlling gene expression in cardiac development. Combined artificial intelligence and whole-genome epigenomic analysis of circulating cell-free DNA in maternal blood has the potential for the detection of fetal congenital heart defects. OBJECTIVE: This study aimed to use genome-wide DNA cytosine methylation and artificial intelligence analyses of circulating cell-free DNA for the minimally invasive detection of fetal congenital heart defects. STUDY DESIGN: In this prospective study, whole-genome cytosine nucleotide methylation analysis was performed on circulating cell-free DNA using the Illumina Infinium MethylationEPIC BeadChip array. Multiple artificial intelligence approaches were evaluated for the detection of congenital hearts. The Ingenuity Pathway Analysis program was used to identify gene pathways that were epigenetically altered and important in congenital heart defect pathogenesis to further elucidate the pathogenesis of isolated congenital heart defects. RESULTS: There were 12 cases of isolated nonsyndromic congenital heart defects and 26 matched controls. A total of 5918 cytosine nucleotides involving 4976 genes had significantly altered methylation, that is, a P value of <.05 along with ≥5% whole-genome cytosine nucleotide methylation difference, in congenital heart defect cases vs controls. Artificial intelligence analysis of the methylation data achieved excellent congenital heart defect predictive accuracy (areas under the receiver operating characteristic curve, ≥0.92). For example, an artificial intelligence model using a combination of 5 whole-genome cytosine nucleotide markers achieved an area under the receiver operating characteristic curve of 0.97 (95% confidence interval, 0.87-1.0) with 98% sensitivity and 94% specificity. We found epigenetic changes in genes and gene pathways involved in the following important cardiac developmental processes: "cardiovascular system development and function," "cardiac hypertrophy," "congenital heart anomaly," and "cardiovascular disease." This lends biologic plausibility to our findings. CONCLUSION: This study reported the feasibility of minimally invasive detection of fetal congenital heart defect using artificial intelligence and DNA methylation analysis of circulating cell-free DNA for the prediction of fetal congenital heart defect. Furthermore, the findings supported an important role of epigenetic changes in congenital heart defect development.

The value of pretreatment glucose-to-lymphocyte ratio for predicting survival of metastatic gastric cancer.

Aim: To demonstrate the prognostic importance of glucose-to-lymphocyte ratio (GLR) in metastatic gastric cancer (mGC). Methods: Retrospectively, 159 mGC patients were enrolled. Kaplan-Meier curve and Cox regression analysis were used to determine the prognostic value of the systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI) and GLR. Results: Progression-free survival (PFS) and overall survival (OS) were associated with NLR, PNI, SII and GLR by univariate analysis. Moreover, OS was associated with Eastern Cooperative Oncology Group performance status and the chemotherapy regimen. In multivariate analysis, only GLR was found to be independently prognostic for both PFS and OS. Conclusion: In mGC, GLR may be a new prognostic marker for both OS and PFS.

Gastric cancer (GC) is the fourth cause of cancer-related deaths. Although different treatment algorithms, including immunotherapy, are applied in patients with unresectable or disseminated (metastatic) GC (mGC), survival results are not yet at the desired level. Different markers are being investigated to measure the response of cancer to treatment in these patients. Many studies have been conducted in this direction with the thought that the prognosis of these cancers will be affected by the patient's own immune response and nutritional status. Despite this, standard markers have not been established to predict cancer-related survival. Studies have shown a relationship between GC and glucose metabolism processes. Recently, a fasting blood glucose-to-lymphocyte count ratio (GLR) marker was developed that simultaneously evaluates both glucose metabolism and the patient's immune response. GLR was found to be effective in predicting survival time in cancers such as gallbladder cancer and hepatocellular carcinoma. However, the effect of GLR on survival in mGC is unclear. In this study, the authors investigated the prognostic significance of GLR in mGC. They found that low GLR was associated with longer survival in mGC. GLR may be a prognostic marker for survival in patients with mGC.

Does Rotation and Anterior Translation Persist as Residual Instability in the Knee after Anterior Cruciate Ligament Reconstruction? (Evaluation of Coronal Lateral Collateral Ligament Sign, Tibial Rotation, and Translation Measurements in Postoperative MRI).

Purpose: The aim of this study was to evaluate the presence of residual instability in the knee after ACL reconstruction through the analysis of MRI findings. Methods: This study included patients who underwent isolated ACL reconstruction between December 2019 and December 2021, and had preoperative and postoperative MRI, clinical scores, and postoperative isokinetic measurements. The anterior tibial translation (ATT) distance, coronal lateral collateral ligament (LCL) sign, and femorotibial rotation (FTR) angle were compared preoperatively and postoperatively. The correlation between the changes in preoperative-postoperative measurements and postoperative measurements with clinical scores and isokinetic measurements was examined. The clinical outcomes were compared based on the presence of a postoperative coronal LCL sign. Inclusion criteria were set as follows: the time between the ACL rupture and surgery being 6 months, availability of preoperative and postoperative clinical scores, and objective determination of muscle strength using isokinetic dynamometer device measurements. Patients with a history of previous knee surgery, additional ligament injuries other than the ACL, evidence of osteoarthritis on direct radiographs, cartilage injuries lower limb deformities, and contralateral knee injuries were excluded from this study. Results: This study included 32 patients. After ACL reconstruction, there were no significant changes in the ATT distance (preoperatively: 6.5 ± 3.9 mm, postoperatively: 5.7 ± 3.2 mm) and FTR angle (preoperatively: 5.4° ± 2.9, postoperatively: 5.2° ± 3.5) compared to the preoperative measurements (p > 0.05). The clinical measurements were compared based on the presence of a postoperative coronal LCL sign (observed in 17 patients, not observed in 15 patients), and no significant differences were found for all parameters (p > 0.05). There were no observed correlations between postoperative FTR angle, postoperative ATT distance, FTR angle change, and ATT distance change values with postoperative clinical scores (p > 0.05). Significant correlations were observed between the high strength ratios generated at an angular velocity of 60° and a parameters FTR angle and ATT distance (p-values: 0.028, 0.019, and r-values: -0.389, -0.413, respectively). Conclusions: Despite undergoing ACL reconstruction, no significant changes were observed in the indirect MRI findings (ATT distance, coronal LCL sign, and FTR angle). These results suggest that postoperative residual tibiofemoral rotation and tibial anterior translation may persist; however, they do not seem to have a direct impact on clinical scores. Furthermore, the increase in tibial translation and rotation could potentially negatively affect the flexion torque compared to the extension torque in movements requiring high torque at low angular velocities.

Lipegfilgrastim may cause hyperleukocytosis.

INTRODUCTION: Granulocyte colony-stimulating factors (G-CSF) are utilized both in the treatment and prophylaxis of chemotherapy-induced neutropenia. Lipegfilgrastim is a long-acting G-CSF. Albeit it provides ease of administration compared to short-acting GCSFs, some lipegfilgrastim-related adverse events may occur. Bone pain, widespread body pain, and feeling of fever are among common adverse effects, while rare but more serious adverse effects such as leukocytosis, spleen rupture, interstitial pneumonia, acute respiratory distress syndrome, capillary leak syndrome, hypokalemia, and glomerulonephritis may occur as well. CASE REPORT: We reported a case of hyperleukocytosis that developed due to prophylactic administration of lipegfilgrastim following the first course of neoadjuvant pertuzumab (840-420 mg), trastuzumab (8-6mg/kg), and docetaxel (75 mg/m2) in a 45-year-old female patient with a diagnosis of breast invasive ductal carcinoma. The patient, who presented with weakness, loss of appetite, and oral intake disorder, had elevated white blood cell (WBC), lactate dehydrogenase (LDH), and uric acid levels in her test results. Peripheral smear (PS) had a left shift. MANAGEMENT AND OUTCOME: Intravenous 0.9% NaCl and peroral allopurinol were started to be administered to the patient. On the ninth day of hospitalization, the patient's clinical manifestation improved, and her WBC, LDH, uric acid, and PS returned to normal. Besides, the progression to tumor lysis syndrome (TLS) was prevented by appropriate hydration and allopurinol treatment. In subsequent chemotherapies (CTs), lipegfilgrastim was discontinued and filgrastim was started. The patient whose hyperleukocytosis did not recur was operated on following neoadjuvant CT. The patient's routine follow-up continues without any problems. DISCUSSION: Although lipegfilgrastim-induced hyperleukocytosis has not been reported in the literature, it should be borne in mind that hyperleukocytosis and related complications may occur, as in our case.

[de novo hATTR amyloidosis after domino transplantation of a donor's liver: a case report for the use of Patisiran]. / de novo hATTR Amyloidose nach Domino-Lebertransplantation: Ein Fallbeispiel für den Einsatz von Patisiran.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, rapidly progressing, and potentially life-threatening disease caused by one of more than 120 mutations in the transthyretin (TTR) gene. As a result of the cumulative amyloid deposits, especially in the peripheral nerves and the heart, the majority of patients develop progressive, peripheral sensorimotor polyneuropathy and biventricular cardiomyopathy over time.Since TTR - and its amyloidogenic variants too - is predominantly synthesized in the liver, early, orthotopic liver transplantation (LTx) is a treatment option that can be used to potentially stop the progression of hATTR amyloidosis.The actual case shows a patient with hepatocellular carcinoma who received the organ of a patient with hATTR as part of a domino liver transplantation. After approximately 10 years, the patient started to develop the characteristic symptoms of the metabolic disorder. Because of a further progression of the amyloidosis, therapy with the RNA interference therapeutic patisiran was initiated, which temporarily halted the progression.

Is biofeedback-assisted pelvic floor muscle training superior to pelvic floor muscle training alone in the treatment of dysfunctional voiding in women? A prospective randomized study.

PURPOSE: To compare the effectiveness of biofeedback-assisted pelvic floor muscle training (PFMT) and PFMT alone on voiding parameters in women with dysfunctional voiding (DV). MATERIALS AND METHODS: The patients in group 1 (34 patients) were treated with biofeedback-assisted PFMT, and the patients in group 2 (34 patients) were treated with PFMT alone for 12 weeks. The 24-hour frequency, average voided volume, maximum urine flow rate (Qmax), average urine flow rate (Qave), post-void residual urine volume (PVR), and the validated Turkish Urogenital Distress Inventory (UDI-6) symptom scores were recorded before and after 12 weeks of treatment. RESULTS: At the end of treatment sessions, the Qmax and Qave values of the patients in group 1 were significantly higher than those in group 2, and the PVR in the patients in group 1 was significantly lower than those in group 2 (p=.026, .043, and .023, respectively). The average UDI-6 symptom scores of the patients in group 1 were significantly lower than those in group 2 (p=.034). Electromyography activity during voiding, in group 1 was significantly lower than in group 2 (41.2 vs. 64.7, respectively, p=.009). CONCLUSION: Biofeedback-assisted PFMT is more effective than PFMT alone in improving clinical symptoms, uroflowmetry parameters, and EMG activity during voiding.

Post-Operative Results of ACL Reconstruction Techniques on Single-Leg Hop Tests in Athletes: Hamstring Autograft vs. Hamstring Grafts Fixed Using Adjustable Cortical Suspension in Both the Femur and Tibia.

Background and Objectives: Anterior cruciate ligament (ACL) tears are common injuries in the athletic population, and accordingly, ACL reconstruction (ACLR) is among the most common orthopedic surgical procedures performed in sports medicine. This study aims to compare the semitendinosus/gracilis (ST/G) and ACL hamstring grafts fixed using adjustable cortical suspension in both the femur and tibia (MAI) ACLR techniques. We aimed to compare the results of single-leg hop tests (SLHT) applied in different directions and limb symmetry indices (LSI) in athletes with a 6-month post-operative ACLR history. Materials and Methods: A retrospective cohort of 39 athletes from various sports branches who underwent MAI (n = 16) and ST/G (n = 23) ACLR techniques by the same surgeon were evaluated. The knee strength of the participants on the operated and non-operated sides was evaluated with five different SLHTs. The SLHT included the single hop for distance (SH), triple hop for distance (TH), crossover triple hop for distance (CH), medial side triple hop for distance (MSTH), and medial rotation (90°) hop for distance (MRH). Results: There was a significant improvement in the mean Lysholm, Tegner, and IKDC scores in the post-operative leg for both techniques (p < 0.05) compared to the pre-operative levels. When there was a difference between the SH of the operative and the non-operative legs in the ST/G technique (p < 0.05), there was no significant difference in the other hop distance for both ST/G and MAI (p > 0.05). There was no difference between the techniques regarding the LSI scores. Conclusions: The fact that our research revealed similar LSI rates of the SLHTs applied in different directions in the ST/G and MAI techniques assumes that the MAI technique can be an ACLR technique which can be functionally used in athletes.

Electromyographic responses of knee isokinetic and single-leg hop tests in athletes :dominant vs. non-dominant sides.

The purpose of the study is to perform the electromyographic (EMG) analysis of isokinetic and single-leg hop tests (SLHTs). We included 20 healthy male athletes (age: 23.18 years, height: 178.82 cm, weight: 73.76 kg and BMI: 47 kg/m2) voluntarily. Isokinetic knee strength tests at at 60°sec-1, 180°sec-1, 240°sec-1 velocities and different SLHTs; Single leg (SL), Triple leg (THD) and Crossover (CHD) hop for distance tests, 6 m timed-hop test (6 m THT), Single leg vertical jump test (VJ) were measured. Muscle activations of quadriceps (Q); vastus medialis (VM), vastus lateralis (VL), rectus femoris (RF) and hamstring (H); biceps femoris (BF) were obtained. There were significant differences in SL, THD, CHD and VJ in DS (p < 0.05).VJ revealed a statistical significance in NDS (p = 0.003). The comparison of the activations produced by the same muscles in different tests showed statistically significant differences in all the muscles for both sides (p < 0.05). In conclusion, we determined that the muscles produce similar activations in the isokinetic tests for both the DS and NDS, whereas there are differences in some of the SLHTs. The most active muscles were VM and RF (medial muscles) in isokinetic tests, and VL (lateral muscle) in SLHTs.g.

Prognostic significance of hemoglobin-to-red cell distribution width ratio in patients with metastatic renal cancer.

The aim of the current research was to investigate the prognostic significance of pretreatment hemoglobin-to-red cell distribution width ratio (HRR) in patients with renal cell carcinoma (RCC). The neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio (LMR) and HRR were analyzed retrospectively to assess their prognostic value using Kaplan-Meier curves and Cox regression analysis in 198 patients with RCC. High HRR (0.72) and high LMR (2.43) were found to be associated with longer progression-free survival and overall survival. A multivariate analysis identified International Metastatic Renal Cell Carcinoma Database Consortium prognostic score, tumor stage, node stage, LMR and HRR as independent prognostic factors for progression-free survival, as well as International Metastatic Renal Cell Carcinoma Database Consortium score, neutrophil-to-lymphocyte ratio and HRR for overall survival. HRR is a an independent prognostic parameter predicting the progression and survival of patients with RCC.

Lay abstract Hemoglobin-to-red cell distribution width ratio (HRR) may be associated with lifespan in patients with cancer, as shown in previous studies of solid organ malignancy. The present study investigates the prognostic significance of pretreatment HRR in patients with renal cell carcinoma. A higher HRR was associated with longer survival in the present study, indicating the value of HRR as a predictor of survival and prognosis in renal cancer.

The importance of the glucose-to-lymphocyte ratio in patients with hepatocellular carcinoma treated with sorafenib.

Aim: To show the prognostic significance of the glucose-to-lymphocyte ratio (GLR) in hepatocellular carcinoma (HCC). Patients & methods: A total of 150 patients with advanced HCC who were treated with sorafenib in our center between January 2011 and December 2019 were included in the study retrospectively. Neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index and GLR were analyzed to assess their prognostic value using Kaplan-Meier and Cox regression analysis before and after propensity score matching (PSM). Results: In univariate analysis before and after PSM, albumin-bilirubin grade, neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio, prognostic nutritional index, AFP level and GLR were found to be significantly associated with both progression-free and overall survival. In multivariate analysis before and after PSM, GLR, albumin-bilirubin grade and AFP were determined to be independent prognostic factors for progression-free and overall survival. Conclusion: The GLR prior to sorafenib treatment is a new prognostic biomarker that may predict survival in advanced HCC.

Sigmoid Sinus Thrombosis Followed by Splenic Infarction Due to Imatinib Therapy in a Patient with Gastrointestinal Stromal Tumor; Hematological Side Effects of Imatinib.

Imatinib has an important place as an adjuvant therapy as well as in the treatment of metastatic disease caused by gastrointestinal stromal tumor (GIST), which is one of the common mesenchymal tumors of the gastrointestinal tract. Imatinib is a tyrosine kinase inhibitor and is generally well tolerated. However, it can cause some serious adverse effects. The most common of these are edema on the face and legs, headache, fatigue, nausea, vomiting, and rash on the skin. The most serious side effects, albeit less common, are gastrointestinal or intraabdominal bleeding. However, thrombotic events such as sigmoid sinus thrombosis and splenic infarction are extremely rare. The current report presents a patient with GIST who is treated with imatinib 400 mg/day. The patient presented with edema on the face and headache in the second month of imatinib therapy, after which she was diagnosed with sigmoid sinus thrombosis. The patient who presented with abdominal pain approximately three months later developed splenic infarction. She was administered acetylsalicylic acid, supplemental oxygen (O2) in the first episode of thrombosis, and imatinib therapy was discontinued. The patient's complaints and thrombus regressed, after which imatinib therapy was resumed. She was administered intravenous hydration, supplemental oxygen, analgesics, and imatinib therapy was discontinued after the patient sustained splenic infarction. After resolution of sigmoid sinus thrombosis and the regression of splenic infarction area, the patient was switched to sunitinib therapy. She is attending routine control visits. Sigmoid sinus thrombosis and splenic infarction should be kept in mind as a rare cause of headache and abdominal pain in patients treated with imatinib, and detailed neurological and gastrointestinal evaluation should be performed.

Sleep-Disordered Breathing and Nocturnal Hypoxemia in Precapillary Pulmonary Hypertension: Prevalence, Pathophysiological Determinants, and Clinical Consequences.

BACKGROUND AND OBJECTIVE: The clinical relevance and interrelation of sleep-disordered breathing and nocturnal hypoxemia in patients with precapillary pulmonary hypertension (PH) is not fully understood. METHODS: Seventy-one patients with PH (age 63 ± 15 years, 41% male) and 35 matched controls were enrolled. Patients with PH underwent clinical examination with assessment of sleep quality, daytime sleepiness, 6-minute walk distance (6MWD), overnight cardiorespiratory polygraphy, lung function, hypercapnic ventilatory response (HCVR; by rebreathing technique), amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac MRI (n = 34). RESULTS: Prevalence of obstructive sleep apnea (OSA) was 68% in patients with PH (34% mild, apnea-hypopnea index [AHI] ≥5 to <15/h; 34% moderate to severe, AHI ≥15/h) versus 5% in controls (p < 0.01). Only 1 patient with PH showed predominant central sleep apnea (CSA). Nocturnal hypoxemia (mean oxygen saturation [SpO2] <90%) was present in 48% of patients with PH, independent of the presence of OSA. There were no significant differences in mean nocturnal SpO2, self-reported sleep quality, 6MWD, HCVR, and lung and cardiac function between patients with moderate to severe OSA and those with mild or no OSA (all p > 0.05). Right ventricular (RV) end-diastolic (r = -0.39; p = 0.03) and end-systolic (r = -0.36; p = 0.04) volumes were inversely correlated with mean nocturnal SpO2 but not with measures of OSA severity or daytime clinical variables. CONCLUSION: OSA, but not CSA, is highly prevalent in patients with PH, and OSA severity is not associated with nighttime SpO2, clinical and functional status. Nocturnal hypoxemia is a frequent finding and (in contrast to OSA) relates to structural RV remodeling in PH.

Targeted metabolomics highlights perturbed metabolism in the brain of autism spectrum disorder sufferers.

INTRODUCTION: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by deficiencies in social interactions and communication, combined with restricted and repetitive behavioral issues. OBJECTIVES: As little is known about the etiopathophysiology of ASD and early diagnosis is relatively subjective, we aim to employ a targeted, fully quantitative metabolomics approach to biochemically profile post-mortem human brain with the overall goal of identifying metabolic pathways that may have been perturbed as a result of the disease while uncovering potential central diagnostic biomarkers. METHODS: Using a combination of 1H NMR and DI/LC-MS/MS we quantitatively profiled the metabolome of the posterolateral cerebellum from post-mortem human brain harvested from people who suffered with ASD (n = 11) and compared them with age-matched controls (n = 10). RESULTS: We accurately identified and quantified 203 metabolites in post-mortem brain extracts and performed a metabolite set enrichment analyses identifying 3 metabolic pathways as significantly perturbed (p < 0.05). These include Pyrimidine, Ubiquinone and Vitamin K metabolism. Further, using a variety of machine-based learning algorithms, we identified a panel of central biomarkers (9-hexadecenoylcarnitine (C16:1) and the phosphatidylcholine PC ae C36:1) capable of discriminating between ASD and controls with an AUC = 0.855 with a sensitivity and specificity equal to 0.80 and 0.818, respectively. CONCLUSION: For the first time, we report the use of a multi-platform metabolomics approach to biochemically profile brain from people with ASD and report several metabolic pathways which are perturbed in the diseased brain of ASD sufferers. Further, we identified a panel of biomarkers capable of distinguishing ASD from control brains. We believe that these central biomarkers may be useful for diagnosing ASD in more accessible biomatrices.