Inflammatory parameters in NSCLC with driver mutation.

Aim: The tumor microenvironment of NSCLC with driver mutations, such as EGFR, ALK and ROS, is less inflammatory. Materials & methods: This retrospective study included 38 patients with NSCLC driver mutations. The relationship between clinical and inflammatory markers concerning progression-free survival and overall survival was analyzed based on Kaplan-Meier curves. Results: The mean age of the patients was 59.8 ± 11.9. Progression-free survival and overall survival were significantly longer in patients under 65 years of age and with low neutrophil-lymphocyte ratio, low systemic immune-inflammation index and high lymphocyte count (p < 0.05). Conclusion: Unlike tumor biology, peripheral inflammatory parameters, such as neutrophil-lymphocyte ratio, systemic immune-inflammation index and lymphocyte count may be associated with survival in NSCLC patients with driver mutations.

Lung cancer is the most common cancer worldwide and has a high mortality rate. Overall survival expectancy in metastatic NSCLC has increased from 11 months to 18 months. The detection of targeting mutations and the introduction of targeted treatments are the factors that increase overall survival. The contribution of immunotherapy to NSCLC is indisputable. The contribution of immunotherapy is low in NSCLC with driver mutation. We found that survival was associated with peripheral parameter indicators of inflammation despite the less inflamed tumor microenvironment. For immunotherapy to be effective in NSCLC, where there are not many treatment options, investigating different immune checkpoints or escape mechanisms and treatment planning for these will further improve survival.

Peripheral inflammatory parameters may be associated with survival in driver mutation NSCLC, in contrast to a less inflammatory tumor microenvironment.

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.

Intense 68 Ga-OncoFAP Uptake as a New Promising Diagnostic Biomarker in Cardiac Sarcoidosis.

ABSTRACT: A 72-year-old man revealed typical findings of cardiac sarcoidosis on cardiovascular MRI. However, 18 F-FDG PET showed no hypermetabolism. Therefore, immunosuppression was not initiated. After 2 years, ventricular arrhythmias and heart failure worsened. 68 Ga-fibroblast activation protein inhibitor PET was initiated to evaluate potential adverse remodeling due to progressive myocardial fibrosis. A second 18 F-FDG PET still revealed no hypermetabolism, and the patient received an implanted cardioverter defibrillator after electrophysiological risk stratification. We present a case of intense fibroblast activation despite a missing 18 F-FDG uptake (mismatch).

Effects of Transcranial Direct Current Stimulation on Motor and Cognitive Dysfunction in an Experimental Traumatic Brain Injury Model.

AIM: To investigate the therapeutic and neuroprotective effects of transcranial direct current stimulation (tDCS) application on the traumatic brain injury (TBI)-induced glutamate and calcium excitotoxicity and loss of motor and cognitive functions. MATERIAL AND METHODS: Forty rats were equally divided in the sham, TBI, tDCS + TBI + tDCS, and TBI + tDCS groups. Mild TBI was induced by dropping a 450-g iron weight from a height of 1 m onto the skull of the rats. The tDCS + TBI + tDCS group was prophylactically administered 1 mA stimulation for 30 min for 7 days starting 5 days before inducing TBI. In the TBI + tDCS group, tDCS (1 mA for 30 min) was administered 2 h after TBI, on days 1 and 2. Cognitive and locomotor functions were assessed using the novel object recognition and open field tests. The calcium, glutamate, and N-methyl-D-aspartate receptor 1 (NMDAR1) levels in the hippocampus were measured using enzyme-linked immunosorbent assay. RESULTS: Although the motor and cognitive functions were substantially reduced in the TBI group when compared with the sham, they improved in the treatment groups (p < 0.05). The calcium, glutamate, and NMDAR1 levels were considerably higher in the TBI group than in the sham (p < 0.001). However, they were considerably lower in the tDCS + TBI + tDCS and TBI + tDCS groups than in the TBI groups (p < 0.05). In particular, the change in the tDCS + TBI + tDCS group was higher than that in the TBI + tDCS group. CONCLUSION: Application of tDCS before the development of TBI improved motor and cognitive dysfunction. It demonstrated a neuroprotective and therapeutic effect by reducing the excitotoxicity via the regulation of calcium and glutamate levels.

Fatigue of the intrinsic foot core muscles had a greater effect on gait than extrinsic foot core muscles: A time-series based analyze.

BACKGROUND: The Heel Rise endurance (HRE) which indicates the extrinsic foot core (ECO) muscle's performance and the paper grip endurance (PGE) which indicates the intrinsic foot core (ICO) muscle's performance are essential components of a healthy foot function. However, the foot core muscles' fatigue response on spatial and temporal gait parameters after the HRE and the PGE tests were not adequately investigated. The purpose of this study was to determine whether the fatigue of the ICO and the ECO muscles affect gait parameters. MATERIAL AND METHODS: A prospective, cross-sectional study was conducted on 22 sedentary individuals (44 feet). Gait was investigated pre and after the Heel Rise (HR) endurance test and the paper grip (PG) endurance test by inertial sensors. At least 500 consecutive steps were collected for each individual. Spatial-temporal gait parameters were used as outcome measures. RESULTS: ECO fatigue and ICO fatigue led to increases in the step length (p < 0.05) and the stride lengths (p < 0.05), the single support (p < 0.05), and the terminal stance durations (p < 0.05). It was also seen that ICO fatigue had a greater effect on gait than ECO fatigue. The ECO fatigue had a medium to large effect on the gait parameters (d=0.313-0.646). The ICO fatigue affected gait with a large effect (d=0.524-2.048). CONCLUSION: The ECO fatigue and the ICO fatigue led to clinically important changes in long-range gait parameters and the ICO fatigue had a greater effect on gait than ECO fatigue. It was suggested that clinicians add ICO muscle endurance training to improve the physical performance of individuals.

Cardiac Sarcoidosis-Diagnostic and Therapeutic Challenges.

Sarcoidosis is a multisystem disorder of unknown etiology. The leading hypothesis involves an antigen-triggered dysregulated T-cell-driven immunologic response leading to non-necrotic granulomas. In cardiac sarcoidosis (CS), the inflammatory response can lead to fibrosis, culminating in clinical manifestations such as atrioventricular block and ventricular arrhythmias. Cardiac manifestations frequently present as first and isolated signs or may appear in conjunction with extracardiac manifestations. The incidence of sudden cardiac death (SCD) is high. Diagnosis remains a challenge. For a definite diagnosis, endomyocardial biopsy (EMB) is suggested. In clinical practice, compatible findings in advanced imaging using cardiovascular magnetic resonance (CMR) and/or positron emission tomography (PET) in combination with extracardiac histological proof is considered sufficient. Management revolves around the control of myocardial inflammation by employing immunosuppression. However, data regarding efficacy are merely based on observational evidence. Prevention of SCD is of particular importance and several guidelines provide recommendations regarding device therapy. In patients with manifest CS, outcome data indicate a 5-year survival of around 90% and a 10-year survival in the range of 80%. Data for patients with silent CS are conflicting; some studies suggest an overall benign course of disease while others reported contrasting observations. Future research challenges involve better understanding of the immunologic pathogenesis of the disease for a targeted therapy, improving imaging to aid early diagnosis, assessing the need for screening of asymptomatic patients and randomized trials.

Effect of hyperbaric oxygen treatment on ischaemia-reperfusion injury in rats detorsioned after experimental ovarian torsion.

Introduction: This study aimed to investigate whether hyperbaric oxygen treatment (HBOT) could ameliorate ischaemia-reperfusion injury in a rat model of ovarian torsion-detorsion. Methods: Twenty-seven rats were divided among four groups: surgical sham rats (S) (n = 6) underwent identical anaesthesia and surgical incisions to other groups (n = 7 per group) but with no ovary intervention; torsion rats (T) underwent laparotomy, ovarian torsion, relaparotomy and sacrifice after three hours; torsion and detorsion rats (T/DT) underwent laparotomy, ovarian torsion (three hours), relaparotomy and detorsion, and sacrifice after one week; torsion, detorsion, hyperbaric oxygen rats (T/DT/HBOT) underwent laparotomy, ovarian torsion, relaparotomy and detorsion, and sacrifice after one week during which HBOT was provided 21 times (100% oxygen at 600 kPa for 50 min). In all groups blood collection for markers of oxidative stress or related responses, and ovary collection for histology were performed after sacrifice. Results: When the T/DT, and T/DT/HBOT groups were compared, 8-hydroxy-2'-deoxyguanosine (a marker of oxidative damage to DNA) and malondialdehyde (a product of lipid peroxidation) levels were lower in the T/DT/HBOT group. Anti-Mullerian hormone levels were higher in the T/DT/HBOT group compared to the T/DT group. In addition, oedema, vascular occlusion, neutrophilic infiltration and follicular cell damage were less in the T/DT/HBOT group than in the T/DT group. Conclusions: When biochemical and histopathological findings were evaluated together, HBOT appeared reduce ovarian ischaemia / reperfusion injury in this rat model of ovarian torsion-detorsion.

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.

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.

Metabolomics: An Emerging "Omics" Platform for Systems Biology and Its Implications for Huntington Disease Research.

Huntington's disease (HD) is a progressive, fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. The precise mechanisms of HD progression are poorly understood; however, it is known that there is an expansion of the trinucleotide cytosine-adenine-guanine (CAG) repeat in the Huntingtin gene. Important new strategies are of paramount importance to identify early biomarkers with predictive value for intervening in disease progression at a stage when cellular dysfunction has not progressed irreversibly. Metabolomics is the study of global metabolite profiles in a system (cell, tissue, or organism) under certain conditions and is becoming an essential tool for the systemic characterization of metabolites to provide a snapshot of the functional and pathophysiological states of an organism and support disease diagnosis and biomarker discovery. This review briefly highlights the historical progress of metabolomic methodologies, followed by a more detailed review of the use of metabolomics in HD research to enable a greater understanding of the pathogenesis, its early prediction, and finally the main technical platforms in the field of metabolomics.

The longitudinal biochemical profiling of TBI in a drop weight model of TBI.

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide, particularly among individuals under the age of 45. It is a complex, and heterogeneous disease with a multifaceted pathophysiology that remains to be elucidated. Metabolomics has the potential to identify metabolic pathways and unique biochemical profiles associated with TBI. Herein, we employed a longitudinal metabolomics approach to study TBI in a weight drop mouse model to reveal metabolic changes associated with TBI pathogenesis, severity, and secondary injury. Using proton nuclear magnetic resonance (1H NMR) spectroscopy, we biochemically profiled post-mortem brain from mice that suffered mild TBI (N = 25; 13 male and 12 female), severe TBI (N = 24; 11 male and 13 female) and sham controls (N = 16; 11 male and 5 female) at baseline, day 1 and day 7 following the injury. 1H NMR-based metabolomics, in combination with bioinformatic analyses, highlights a few significant metabolites associated with TBI severity and perturbed metabolism related to the injury. We report that the concentrations of taurine, creatinine, adenine, dimethylamine, histidine, N-Acetyl aspartate, and glucose 1-phosphate are all associated with TBI severity. Longitudinal metabolic observation of brain tissue revealed that mild TBI and severe TBI lead distinct metabolic profile changes. A multi-class model was able to classify the severity of injury as well as time after TBI with estimated 86% accuracy. Further, we identified a high degree of correlation between respective hemisphere metabolic profiles (r > 0.84, p < 0.05, Pearson correlation). This study highlights the metabolic changes associated with underlying TBI severity and secondary injury. While comprehensive, future studies should investigate whether: (a) the biochemical pathways highlighted here are recapitulated in the brain of TBI sufferers and (b) if the panel of biomarkers are also as effective in less invasively harvested biomatrices, for objective and rapid identification of TBI severity and prognosis.

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.

Post-Operative Modified All-Inside ACL Reconstruction Technique's Clinical Outcomes and Isokinetic Strength Assessments.

BACKGROUND AND OBJECTIVE: Anterior cruciate ligament (ACL) injuries are very common among the athletic population. ACL reconstruction (ACLR) performed because of these injuries is one of the procedures performed by orthopedic surgeons using different grafting methods. This study aims to compare the data related to post-operative 6-month isokinetic strength values, strength-related asymmetry rates, time parameters, and joint angle in athletes who underwent ACLR with the Modified All-inside (4ST) technique, on both the healthy knee (HK) and the ACLR-applied sides. MATERIALS AND METHODS: A total of 20 athletes from various sports on whom the 4ST ACLR technique had been applied by the same surgeon were evaluated retrospectively. Lysholm, Tegner, and International Knee Documentation Committee (IKDC) scores of the patients were obtained pre-operative and at 6 months post-operative. Isokinetic knee extension (Ex) and flexion (Flx) strengths on the HK and ACLR sides of the patients were evaluated with a series of four different angular velocities (60, 180, 240, and 300°/s). In addition to peak torque (PT) and hamstring/quadriceps ratio (H/Q) parameters, the findings were also evaluated with additional parameters such as joint angle at peak torque (JAPT), time to peak torque (TPT), reciprocal delay (RD), and endurance ratio (ER). RESULTS: There was a significant improvement in the mean Lysholm, Tegner, and IKDC scores after surgery compared with pre-operative levels (p < 0.05). As for PT values, there were significant differences in favor of the HK in the 60, 180, and 300°/s Ex phases (p < 0.05). In terms of the H/Q and (hamstring/hamstring)/(quadriceps/quadriceps) (HH/QQ) ratios, there were significant differences at 300°/s (p < 0.05). In terms of JAPT, there were significant differences in the 300°/s Ex and 180°/s Flx phases (p < 0.05). In terms of TPT, there were significant differences in the 300°/s Ex phase (p < 0.05). In terms of RD and ER, no significant difference was observed between the HK and ACLR sides at any angular velocity. CONCLUSIONS: Although differences were observed in PT values, particularly in the Ex phase, this did not cause a significant change in H/Q ratios. Similar results were observed for additional parameters such as JAPT, TPT, RD, and ER. The results show that this ACLR technique can be used in athletes in view of strength gain and a return to sports.

Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington's Disease Brain Tissue.

The impact of environmental factors on epigenetic changes is well established, and cellular function is determined not only by the genome but also by interacting partners such as metabolites. Given the significant impact of metabolism on disease progression, exploring the interaction between the metabolome and epigenome may offer new insights into Huntington's disease (HD) diagnosis and treatment. Using fourteen post-mortem HD cases and fourteen control subjects, we performed metabolomic profiling of human postmortem brain tissue (striatum and frontal lobe), and we performed DNA methylome profiling using the same frontal lobe tissue. Along with finding several perturbed metabolites and differentially methylated loci, Aminoacyl-tRNA biosynthesis (adj p-value = 0.0098) was the most significantly perturbed metabolic pathway with which two CpGs of the SEPSECS gene were correlated. This study improves our understanding of molecular biomarker connections and, importantly, increases our knowledge of metabolic alterations driving HD progression.

[Diagnostics of cardiac amyloidosis]. / Diagnostik der kardialen Amyloidose.

The early diagnosis of cardiac amyloidosis is decisive for the success of treatment of affected persons. The thorough clinical investigation of the patient should be followed by appropriate diagnostics using modern procedures. The main symptoms are dyspnea, loss of performance and edema and in later stages cardiac arrhythmias in the form of atrioventricular conduction disturbances and atrial fibrillation but ventricular arrhythmias occur more rarely. During heart failure due to cardiac amyloidosis an increase of cardiac enzymes frequently occurs (e.g., creatine kinase, troponin, N­terminal pro-brain natriuretic peptide), which can be included in the risk stratification and treatment monitoring, taking certain limitations into consideration. The investigation of light chains in serum and/or urine should be carried out immediately, as soon as there is a clinical and echocardiographic suspicion of cardiac amyloidosis. Subsequently, either cardiac magnetic resonance imaging (MRI) or bone scintigraphy should be carried out, depending on the locally available options. Depending on the results of these two imaging procedures, a decision must be made as to whether further diagnostic steps (e.g., endomyocardial biopsy) are necessary. In the last decade bone scintigraphy has proven to be a blessing for the diagnostics of cardiac amyloidosis but many partial aspects and limitations necessitate special and careful consideration. A Perugini score of 2 or 3 is initially "indicative" of cardiac amyloidosis but not yet "confirmative" for a specific subtype. Only after an additional negative result of the light chain determination, can the diagnosis of ATTR amyloidosis be noninvasively made. Cardiac amyloidosis shows a particularly characteristic contrast enhancement in cardiac MRI, which mostly begins in the inner (subendocardial) layers of the basal left ventricular (LV) wall and frequently appears to be circular in the cross-sectional view of the left ventricle. Supplementary T1 and extracellular volume fraction mapping results, which are shown as color-coded maps, enable the rapid and elegant assessment of the myocardial structure and the extent of amyloid deposition. An additional investigation of the TTR gene is recommended in the case of ATTR amyloidosis for a differentiation between hereditary and acquired ATTR, as from this, further therapeutic consequences can be derived.

Urinary Cytokines as Potential Biomarkers of Mild Cognitive Impairment and Alzheimer's Disease: A Pilot Study.

Background: Alzheimer's disease (AD) is the most common form of dementia, accounting for 80% of all cases. Mild cognitive impairment (MCI) is a transitional state between normal aging and AD. Early detection is crucial, as irreversible brain damage occurs before symptoms manifest. Objective: This study aimed to identify potential biomarkers for early detection of AD by analyzing urinary cytokine concentrations. We investigated 37 cytokines in AD, MCI, and cognitively normal individuals (NC), assessing their associations with AD development. Methods: Urinary cytokine concentrations were measured in AD (n = 25), MCI (n = 25), and NC (n = 26) patients. IL6ST and MMP-2 levels were compared between AD and NC, while TNFRSF8, IL6ST, and IL-19 were assessed in AD versus MCI. Diagnostic models distinguished AD from NC, and in-silico analysis explored molecular mechanisms related to AD. Results: Significant perturbations in IL6ST and MMP-2 concentrations were observed in AD urine compared to NC, suggesting their potential as biomarkers. TNFRSF8, IL6ST, and IL-19 differed significantly between AD and MCI, implicating them in disease progression. Diagnostic models exhibited promising performance (AUC: 0.59-0.79, sensitivity: 0.72-0.80, specificity: 0.56-0.78) in distinguishing AD from NC. In-silico analysis revealed molecular insights, including relevant non-coding RNAs, microRNAs, and transcription factors. Conclusion: This study establishes significant associations between urinary cytokine concentrations and AD and MCI. IL6ST, MMP-2, TNFRSF8, IL6ST, and IL-19 emerge as potential biomarkers for early detection of AD. In-silico analysis enhances understanding of molecular mechanisms in AD. Further validation and exploration of these biomarkers in larger cohorts are warranted to assess their clinical utility.

Evaluation of Isokinetic Knee Strengths after ACL Reconstruction with Quadrupled Semitendinosus Suspensory Femoral and Tibial Fixation versus Four-Strand Semitendinosus and Gracilis Suspensory Femoral and Tibial Screw Fixation.

INTRODUCTION: The purpose of this study was to demonstrate that patients undergoing ACL reconstruction with quadrupled semitendinosus suspensory femoral and tibial fixation have comparable results in muscle strength and knee function to those undergoing ACL reconstruction with four-strand semitendinosus-gracilis suspensory femoral fixation and a bioabsorbable tibial interference screw fixation. MATERIALS AND METHODS: Between 2017 and 2019, 64 patients who were operated on by the same surgeon were included. Patients underwent ACL reconstruction technique with quadrupled semitendinosus suspensory femoral and tibial button fixation in Group 1, and patients underwent ACL reconstruction with coupled four-strand semitendinosus-gracilis suspensory femoral fixation and a bioabsorbable tibial interference screw in Group 2. Evaluation of patients was performed with the Lysholm and Tegner activity scale preoperatively and at the 1st and 6th months postoperatively. At the 6-month visit, isokinetic testing of the operated and non-operated limbs was performed in both groups. RESULTS: There was no significant difference in the age, weight, and BMI values of the patients in Groups 1 and 2 (p < 0.05). According to the strength values of the operated sides of the patients in Group 1 and Group 2, there was no significant difference in the angular velocities of 60° s-1, 180° s-1, and 240° s-1 in both extension and flexion phases between the operated sides of Groups 1 and 2 (p < 0.05). CONCLUSIONS: Patients who have ACL reconstruction with quadrupled semitendinosus suspensory femoral and tibial fixation have comparable muscle strength and knee function to those who undergo ACL reconstruction with four-strand semitendinosus-gracilis suspensory femoral fixation and a bioabsorbable tibial interference screw.

A case series of double-chambered left ventricle detected by cardiovascular magnetic resonance.

Background: Double-chambered left ventricle (DCLV) is a rare congenital condition, and few case reports are mentioned in literature. Entity, clinical course, and prognosis remain unclear. Cardiovascular magnetic resonance (CMR) is often used for characterization of various congenital heart diseases and can be particularly useful for imaging rare phenomena. Case summary: Three cases of DCLV were detected by CMR within 2 years in our CMR centre with and without associated congenital heart disease or hypertrabecularization. The patients did not suffer from cardiac symptoms despite the presence of premature ventricular complexes in one patient. Diagnosis of DCLV was made based on a first CMR study that was performed in adulthood, although some anatomical suspicion was already raised by previous echocardiography. Discussion: Double-chambered left ventricle, synonymous with the terminus 'cor triventriculare sinistrum', has been previously perceived as a rare phenomenon compared with double-chambered right ventricle. It has to be distinguished from ventricular aneurysm or cardiac diverticulum and is characterized by an additional contractile septum with normal wall structure that divides the LV cavum into two (rather) same-sized chambers. The prognosis seems to be benign, since there is no restriction in functionality and no increased thrombogenicity until adulthood. Consequently, there is (presumably) no need for a tailored therapy-at least in the cases present here. Accordingly, we recommend follow-up CMR examinations for progress monitoring and recognize CMR's significant role for diagnosis and follow-up of cardiac abnormalities in orphan diseases. Due to its broader availability, we expect further cases of DLVC in the future.