Blood-based biomarkers in Alzheimer's disease - moving towards a new era of diagnostics.

Alzheimer's disease (AD), a primary cause of dementia globally, is traditionally diagnosed via cerebrospinal fluid (CSF) measures and positron emission tomography (PET). The invasiveness, cost, and limited accessibility of these methods have led to exploring blood-based biomarkers as a promising alternative for AD diagnosis and monitoring. Recent advancements in sensitive immunoassays have identified potential blood-based biomarkers, such as Aß42/Aß40 ratios and phosphorylated tau (p-tau) species. This paper briefly evaluates the clinical utility and reliability of these biomarkers across various AD stages, highlighting challenges like refining plasma Aß42/Aß40 assays and enhancing the precision of p-tau, particularly p-tau181, p-tau217, and p-tau231. The discussion also covers other plasma biomarkers like neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and synaptic biomarkers, assessing their significance in AD diagnostics. The need for ongoing research and development of robust assays to match the performance of CSF and PET biomarkers is underscored. In summary, blood-based biomarkers are increasingly crucial in AD diagnosis, follow-up, prognostication, treatment response evaluation, and population screening, particularly in primary care settings. These developments are set to revolutionize AD diagnostics, offering earlier and more accessible detection and management options.

Longitudinal plasma phosphorylated-tau217 and other related biomarkers in a non-demented Alzheimer's risk-enhanced sample.

INTRODUCTION: Understanding longitudinal change in key plasma biomarkers will aid in detecting presymptomatic Alzheimer's disease (AD). METHODS: Serial plasma samples from 424 Wisconsin Registry for Alzheimer's Prevention participants were analyzed for phosphorylated-tau217 (p-tau217; ALZpath) and other AD biomarkers, to study longitudinal trajectories in relation to disease, health factors, and cognitive decline. Of the participants, 18.6% with known amyloid status were amyloid positive (A+); 97.2% were cognitively unimpaired (CU). RESULTS: In the CU, amyloid-negative (A-) subset, plasma p-tau217 levels increased modestly with age but were unaffected by body mass index and kidney function. In the whole sample, average p-tau217 change rates were higher in those who were A+ (e.g., simple slopes(se) for A+ and A- at age 60 were 0.232(0.028) and 0.038(0.013))). High baseline p-tau217 levels predicted faster preclinical cognitive decline. DISCUSSION: p-tau217 stands out among markers for its strong association with disease and cognitive decline, indicating its potential for early AD detection and monitoring progression. HIGHLIGHTS: Phosphorylated-tau217 (p-tau217) trajectories were significantly different in people who were known to be amyloid positive. Subtle age-related trajectories were seen for all the plasma markers in amyloid-negative cognitively unimpaired. Kidney function and body mass index were not associated with plasma p-tau217 trajectories. Higher plasma p-tau217 was associated with faster preclinical cognitive decline.

Neurofilament light chain as neuronal injury marker - what is needed to facilitate implementation in clinical laboratory practice?

Neurobiomarkers have attracted significant attention over the last ten years. One promising biomarker is the neurofilament light chain protein (NfL). Since the introduction of ultrasensitive assays, NfL has been developed into a widely used axonal damage marker of relevance to the diagnosis, prognostication, follow-up, and treatment monitoring of a range of neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. The marker is increasingly used clinically, as well as in clinical trials. Even if we have validated precise, sensitive, and specific assays for NfL quantification in both cerebrospinal fluid and blood, there are analytical, as well as pre- and post-analytical aspects of the total NfL testing process, including biomarker interpretation, to consider. Although the biomarker is already in use in specialised clinical laboratory settings, a more general use requires some further work. In this review, we provide brief basic information and opinions on NfL as a biomarker of axonal injury in neurological diseases and pinpoint additional work needed to facilitate biomarker implementation in clinical practice.

Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood.

OBJECTIVES: Neurofilament light chain (NfL) concentration in blood is a biomarker of neuro-axonal injury in the nervous system and there now exist several assays with high enough sensitivity to measure NfL in serum and plasma. There is a need for harmonization with the goal of creating a certified reference material (CRM) for NfL and an early step in such an effort is to determine the best matrix for the CRM. This is done in a commutability study and here the results of the first one for NfL in blood is presented. METHODS: Forty paired individual serum and plasma samples were analyzed for NfL on four different analytical platforms. Neat and differently spiked serum and plasma were evaluated for their suitability as a CRM using the difference in bias approach. RESULTS: The correlation between the different platforms with regards to measured NfL concentrations were very high (Spearman's ρ≥0.96). Samples spiked with cerebrospinal fluid (CSF) showed higher commutability compared to samples spiked with recombinant human NfL protein and serum seems to be a better choice than plasma as the matrix for a CRM. CONCLUSIONS: The results from this first commutability study on NfL in serum/plasma showed that it is feasible to create a CRM for NfL in blood and that spiking should be done using CSF rather than with recombinant human NfL protein.

The evaluation of serum bisphenol A in patients with preeclampsia.

AIMS: High bisphenol A (BPA) concentration may compromise normal placental development. The aim of this study was to determine maternal serum BPA concentrations in pregnant women with complicated preeclampsia (PE) and normal pregnant women, to compare BPA concentrations, and to examine pregnancy outcomes. METHODS: This prospective case-control study was conducted between March 2021 and October 2021. Serum BPA levels of preeclamptic pregnancy and normal pregnancy were statistically evaluated. In addition, the PE group was divided into three subgroups according to the course of pregnancy. Group 1: patients with non-severe PE who delivered at 37 weeks or later, Group 2: patients with severe PE who delivered at less than 34 weeks, Group 3: patients with severe PE who delivered between 34 and 37 weeks. The association between BPA levels and pregnancy outcome was investigated. RESULTS: Forty-six cases in the PE group were compared with 46 cases of normal pregnancies. The median BPA level was 19.46 ng/mL in the PE group and 16.36 ng/mL in the control group. The median BPA levels in the PE group were significantly higher than those in the control group (p = 0.007). Serum BPA levels were significantly lower in women who delivered at 37 weeks or later than in women who delivered at less than 34 weeks due to severe PE (p ≤ 0.018). CONCLUSION: Our study highlights the association between elevated maternal serum levels of BPA and PE. Moreover, knowledge of BPA levels in women with PE may provide information about the prognosis of pregnancy.

Serum ciliary neurotrophic factor levels in children with attention deficit hyperactivity disorder.

Purpose/aim of the study: The study aimed to highlight the possible role of ciliary neurotrophic factor (CNTF) in the pathophysiology of attention deficit hyperactivity disorder (ADHD) and determine whether CNTF can be used as a biomarker for ADHD.Materials and methods: Patients with a diagnosis of ADHD and neurotypical subjects aged 6-12 years were recruited prospectively. The study applied Conners' Teacher Rating Scale (CTRS) to determine the patients' ADHD predominance and severity. Serum CNTF levels were measured with an enzyme-linked immunosorbent assay (ELISA) kit.Results: A total of 43 ADHD patients and 33 healthy controls were included in the study. A significant difference was found between the serum CNTF levels of the ADHD patients (22.17 pg/ml) and the controls (22.80 pg/ml). Correlations between the CNTF levels and CTRS scores were not significant.Conclusions: The study identified an alteration of serum CNTF levels in ADHD patients and thus asserted a link between CNTF and ADHD pathophysiology; children with ADHD had significantly lower serum CNTF levels compared to the neurotypical controls. Further research is needed to understand the mechanisms of CNTF.

Maternal plasma levels of vitamin D in postterm pregnancy.

This study was conducted to examine the levels of vitamin D in postterm pregnancy. The study consisted of two groups: Group 1: women with postterm pregnancy in whom labour has not started (n = 40). Group 2: pregnant women with spontaneous labour between 37 and 41 weeks of gestation (n = 40). Demographic characteristics of individuals, age, body mass index, gravida, parity, living child, number of abortions and birth characteristics were recorded. Prepartum and postpartum haemoglobin (Hb) and haematocrit (Hct) values ​​and vitamin D levels of pregnant women were measured. We found no significant differences in vitamin D levels, smoking, mode of delivery, induction of labour, methods of cervical ripening and maternal and perinatal complications between the groups (p > .05). D vitamin in the model had a statistically significant effect on prepartum Hb (p < .05). Vitamin D levels seem not to be associated with postterm pregnancy. Vitamin D had a statistically significant effect on prepartum Hb.IMPACT STATEMENTWhat is already known on this subject? The aetiology of post term pregnancy is not clearly known, factors such as foetal anencephaly, foetal sex, placental sulfatase deficiency, genetic factors, and high pre-pregnancy body mass index play a role.What do the results of this study add? Vitamin D levels seem not to be associated with postterm pregnancy. Vitamin D had a statistically significant effect on prepartum Hb.What are the implications of these findings for clinical practice and/or further research? Further studies are needed to clarify the relationship between vitamin D levels and postterm pregnancy.

Migraine susceptibility is modulated by food triggers and analgesic overuse via sulfotransferase inhibition.

BACKGROUND/AIM: Certain constituents in migraine food triggers and non-steroidal anti-inflammatory drugs (NSAIDs) inhibit sulfotransferases (SULTs) that detoxify drugs/chemicals and play role in the metabolism of neurotransmitters. We aimed to dissect SULT1A1 modulation of CSD susceptibility and behavior in an in vivo experimental model using hesperidin, a SULT1A1 inhibitor found in citrus fruits (known migraine triggers) and mefenamic acid (SULT1A1 inhibitor), an NSAID to simulate medication overuse. METHODS: Hesperidin was used as SULT1A1 inhibitor found in citrus fruits, known migraine triggers and mefenamic acid (NSAID), another SULT1A1 inhibitor, was used to induce MO in rats. The groups were; 1) Hesperidin (ip) or its vehicle-DMSO (ip) 2) Chronic (4 weeks) mefenamic acid (ip) or its vehicle (ip) 3) Chronic mefenamic acid+hesperidin (ip) or DMSO (ip). CSD susceptibility was evaluated and behavioral testing was performed. SULT1A1 enzyme activity was measured in brain samples. RESULTS: Single-dose of hesperidin neither changed CSD susceptibility nor resulted in any behavioral change. Chronic mefenamic acid exposure resulted in increased CSD susceptibility, mechanical-thermal hypersensitivity, increased head shake, grooming and freezing and decreased locomotion. Single dose hesperidin administration after chronic mefenamic acid exposure resulted in increased CSD susceptibility and mechanical-thermal hypersensitivity, increased freezing and decreased locomotion. SULT1A1 enzyme activity was lower in mefenamic acid and mefenamic acid+hesperidin groups compared to their vehicles. CONCLUSION: Mefenamic acid and hesperidin have synergistic effect in modulating CSD susceptibility and pain behavior. Sulfotransferase inhibition may be the common mechanism by which food triggers and NSAIDs modulate migraine susceptibility. Further investigations regarding human provocation studies using hesperidin in migraine patients with medication overuse are needed.

The evaluation of serum tryptophan and kynurenine levels in patients with obstructive sleep apnea syndrome.

PURPOSE: The kynurenine (Kyn) pathway may play a role in certain physiological functions such as behavior, sleep, thermoregulation, and pregnancy. Tryptophan (Trp) is oxidized with tryptophan 2,3-dioxygenase and indolamine 2,3-dioxygenase (IDO). Under normal conditions, hepatic kynurenine is a transcription factor and IDO expression in healthy tissues is very low. The ratio of Kyn to Trp can be used as an indicator to assess IDO activity. This study aimed to determine the relationship between Kyn/Trp ratio and obstructive sleep apnea syndrome (OSAS) disease activity. METHODS: Study participants were categorized in 3 groups: Group 1 included patients with mild OSAS, Group 2, patients with moderate to severe OSAS, and Group 3, individuals considered normal to serve as controls. The demographic characteristics of the patients were recorded. Apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) measurements were performed by diagnostic polysomnography (PSG). Trp and Kyn levels were determined by HPLC-UV method. RESULTS: Group 1 included 30 patients (18 men) with mild OSAS; Group 2 included 42 patients (31 men) with moderate to severe OSAS; and Group 3 included 25 controls (13 men). While there was no statistically significant difference between the levels of tryptophan and kynurenine in the groups, a significant difference was found between the Kyn/Trp ratios. A significant correlation was observed in individuals with a body mass index less than 25 with the Kyn/Trp ratio. In individuals with mild OSAS, a significant correlation was observed between ODI and BMI. In individuals with moderate to severe OSAS, there was a significant correlation between ODI, AHI, and BMI. CONCLUSION: In this study, there was no relationship between OSAS disease severity and IDO activity as assessed by immunoreactivity via the Kyn/Trp pathway.

Does YouTube include high-quality resources for training on laparoscopic and robotic radical prostatectomy?

PURPOSE: Our aim was to assess the educational quality of the YouTube video content related to laparoscopic and robotic radical prostatectomy (RP). METHODS: An objective scoring tool named as Prostatectomy Assessment and Competency Evaluation (PACE) score was used to measure and quantify seven critical steps in RP including bladder drop, preparation of the prostate, bladder neck dissection, posterior/seminal vesicle dissection, neurovascular bundle preservation, apical dissection, and urethro-vesical anastomosis. A five-point scale was used for grading the seven steps, where a score of 1 and 5 represented the lowest and ideal performance, respectively. Additionally, descriptive statistics including the upload time, video length, view count, number of comments, likes, and dislikes were all recorded. RESULTS: Of the 1688 videos (551 from laparoscopic RP, 567 from robotic RP, and 570 from robot-assisted RP), 226 videos were analyzed after excluding duplicate and irrelevant videos. Robotic/robot-assisted RP videos were found to be statistically longer than laparoscopic RP videos (p = 0.016). The PACE score of urethro-vesical anastomosis step in robotic RP videos was statistically higher than laparoscopic RP videos (p = 0.021). A weak but significant positive correlation between the video length and total PACE score (rho: 0.51; p = 0.04 for laparoscopic RP and rho: 0.43; p = 0.03 for robotic/robot-assisted RP) was found. A weak but positive correlation was also determined between number of likes and total PACE score (rho: 0.39; p = 0.02) for robotic/robot-assisted RP videos. CONCLUSIONS: Although YouTube website includes high-quality videos for both laparoscopic and robotic/robot-assisted RP, there is no objective parameter to predict the educational quality of the videos.

Can serum procalcitonin levels be useful in predicting spontaneous ureteral stone passage?

BACKGROUND: Medical expulsive therapy (MET) is recommended for ureteral stones when there is no indication for interventional treatment. Spontaneous passage (SP) may not always be perceived in patients undergoing MET. We aimed to demonstrate the effects of inflammatory factors on spontaneous ureteral stone passage in patients undergoing MET. METHODS: Our study was conducted between August and November, 2016, in healthy volunteers and patients with a single distal ureteral stone between 5 and 10 mm in diameter and no indications for interventional therapy. Blood and urine samples from all patients and healthy volunteers were tested. The patients were followed up every 2 weeks for 1 month unless emergency situations appeared. Patients with stone-free status at follow-up were concluded to have achieved complete stone passage [SP(+)], and failure [SP(-)] was concluded if the patient had not passed the stone by the end of the study. Blood samples of the patients and the control group were analyzed, recording WBC (white blood cell), CRP (c-reactive protein), SED (sedimentation), MPV (mean platelet volume), NLR (neutrophil-to-lymphocyte ratio), and serum procalcitonin levels. Abnormalities in urine samples were recorded. All patients received diclofenac sodium 75 mg/day, tamsulosin 0.4 mg/day, and at least 3 l/day fluid intake. Patients were followed for a month with kidney, ureter, bladder (KUB) plain films, ultrasonography (USG), and unenhanced abdominal CT scans while undergoing MET. Comparative statistical analyses were performed between the SP(+) and SP(-) groups. RESULTS: The procalcitonin levels of the SP(-) group were significantly higher (207 ± 145.1 pg/ml) than in the SP(+) group (132.7 ± 28.1 pg/ml) (p = 0.000). The leucocyturia rate of the SP(-) group was significantly higher than in the SP(+) group (p = 0.004). Based on the ROC curve analysis, 160 pg/ml (86.7% sensitivity, 70.8% specificity, p < 0.001; AUC: 0.788 95% CI (0.658-0.917) was identified as the optimal cut-off value for procalcitonin. In logistic regression analysis, a significant efficacy of procalcitonin and leucocyturia was observed in the univariate analysis on spontaneous passage. In the multivariate analysis, significant independent activity was observed with procalcitonin. (p < 0.05). CONCLUSION: Our findings suggest that high procalcitonin levels and the presence of leucocyturia have a strong negative effect on SP of ureteral stones between 5 and 10 mm in diameter. This relationship can be explained by stone impaction, possibly caused by increased mucosal inflammation.

Outcomes of intravesical chondroitin-sulfate and combined hyaluronic-acid/chondroitin-sulfate therapy on female sexual function in bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: Our aim was to determine the efficacy of intravesical chondroitin sulfate (CS) and combined hyaluronic acid/chondroitin sufate (HA/CS) treatment and their effects on sexual function of females with interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A total of 68 female patients with IC/BPS between 2012 and 2018 were reviewed. Thirty-three patients were treated with combined HA/CS and 28 patients were treated with CS. Instillations were performed weekly for the first month, biweekly for the second month, and monthly in the third and fourth months. Before and after the sixth month of the treatment, all patients were evaluated with the Female Sexual Function Index (FSFI), visual analog pain scale (VAS), interstitial cystitis symptom index (ICSI), interstitial cystitis problem index (ICPI), and voiding diary, and changes were recorded. RESULTS: A statistically significant improvement was determined for FSFI, VAS, ICSI, and ICPI scores after treatment in both groups. Among baseline characteristics, a weak but significant negative correlation was determined only between the ICSI score improvement and age (rho: -0.38; p = 0.03) on statistical analysis. Compared with CS, combined HA/CS treatment was superior in terms of ICSI, ICPI, and daytime and nighttime frequency improvement (0.042, 0.038, 0.039, and 0.045; respectively). All domains of the sexual function index were significantly improved at the sixth month of intravesical therapy in both groups. A statistical difference was not found between the two groups. CONCLUSIONS: Although it seems that intravesical HA/CS combination is superior to CS alone in terms of symptom reduction, both of them have beneficial effects on sexual function.

Female sexual function following a novel transobturator sling procedure without paraurethral dissection (modified-TOT).

PURPOSE: To determine whether there is a difference in sexual function after modified and classical TOT procedures. MATERIALS AND METHODS: Of the 80 sexually active women with SUI, 36 underwent na original outside-in TOT as described by Delorme, and 44 underwent modified TOT procedure, between 2011 and 2015. The severity of incontinence and sexual function were evaluated using International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Female Sexual Function Index (FSFI) questionnaires preoperatively and 3 months after surgery. RESULTS: The postoperative ICIQ-SF score was significantly lower than the preoperative ICIQ-SF score in both groups (p=0.004 for modified TOT and p=0.002 for classical TOT). There was no significant difference in the ICIQ-SF score reduction between the two groups (14.1±2.1 vs. 14.4±1.9; p=0.892). Complication rates according to the Clavien-Dindo classification were also similar in both groups. In both groups, difference between preoperative and postoperative FSFI scores revealed a statistically significant improvement in all domains. Comparison of postoperative 3-month FSFI scores of modified and classical TOT groups showed statistically significant differences in arousal, lubrication and orgasm domains. Desire, satisfaction, pain and total FSFI scores did not differ significantly between two groups. CONCLUSION: The modified TOT technique is a simple, reliable and minimal invasive procedure. The cure rate of incontinence and complication rates are the same as those of the classical TOT technique. However, due to the positive effects of minimal tissue damage on sexual arousal and orgasmic function, modified TOT has an advantage over the classical TOT.

Outcomes of two different incision techniques for surgical treatment of stress urinary incontinence with concomitant anterior vaginal wall prolapse.

PURPOSE: To assess the outcomes of two different incision techniques used in the surgical treatment of stress urinary incontinence (SUI) with concomitant anterior vaginal wall prolapse and to identify possible associated risk factors with a medium-term follow-up in patients who underwent TOT procedure. METHODS: We conducted a retrospective cohort study of 233 women who underwent transobturator tape procedure with cystocele repair. The women were divided into two groups according to two different incision techniques. The outcomes were analyzed considering five postoperative parameters: objective cure, subjective cure, patient satisfaction, resolution of urgency urinary incontinence and complications. The mean follow-up period was 43.6 months (range 12-85). RESULTS: A total of 226 women were documented in this study: 79 women in single-incision technique (group 1) and 147 women in double-incision technique (group 2). The objective and subjective cure and patient satisfaction (visual analog scale score ≥80) rates were 89.8, 73.4, 84.8 % and 90.4, 74.1, 86.4 % in group 1 and group 2, respectively. Complications reported according to the Clavien-Dindo classification were grade I 5.2 %, grade II 42.1 %, grade IIIa 47.3 %, and grade IIIb 5.2 %, and grade I 22.2 %, grade II 77.7 %, grade IIIa 0 % and grade IIIb 0 % in group 1 and group 2, respectively. The mean operative time was significantly shorter in group 1 compared to group 2 (p = 0.001). CONCLUSIONS: Both incision techniques have satisfactory outcomes in the surgical treatment of SUI with cystocele; nevertheless, the postoperative complications favor the double-incision technique.

Patient and partner outcome of inflatable and semi-rigid penile prosthesis in a single institution.

INTRODUCTION: Penile prostheses are subject to a continuous development and have gained better mechanical reliability and safety during the last decades. In this study, we aimed to investigate the outcomes and satisfaction rates of inflatable penile prosthesis (IPP) and semirigid penile prosthesis (SPP) implantation. MATERIALS AND METHODS: From August 2001 to June 2012, 257 men with erectile dysfunction (ED) underwent penile prosthesis implantation (PPI) at our institution. Of the 257 patients, 118 underwent implantation of IPP and 139 underwent SPP implantation. The pre-operative and post-operative erectile status of the patients were assessed by international index of erectile function (IIEF) questionnaire. The satisfaction of patients and partners were evaluated by a telephone interview using the erectile dysfunction inventory of treatment satisfaction (EDITS) questionnaire and EDITS partner survey. RESULTS: The overall major complication rate was higher in IPP group. PPI led to a significant improvement in IIEF scores in both groups. For IPP and SPP groups the average EDITS scores were 78±11and 57±8, respectively, and that for the partners were 72±10 and 49±7, respectively (p<0.05). CONCLUSION: Although the IPP implantation have better satisfaction rates, the SPP implantation is still a viable treatment option in the surgical treatment of ED because of low cost and high durability with acceptable satisfaction rates.

Does concomitant vaginal prolapse repair affect the outcomes of the transobturator tape procedure in the long term?

INTRODUCTION AND HYPOTHESIS: Little information is available on the effects of concomitant vaginal prolapse repair on the outcomes of the transobturator tape (TOT) procedure. The purpose of this study is to assess the results and complications of TOT when combined with vaginal prolapse repair with a long-term follow-up. METHODS: We conducted a retrospective cohort study of 232 female patients who underwent the TOT procedure at two institutions. There were two groups: group 1 consisted of patients who had undergone TOT alone and group 2 consisted of patients who had undergone concomitant vaginal prolapse repair. The outcomes were analyzed considering four postoperative parameters: objective cure, subjective cure, resolution of urgency urinary incontinence (UUI), and patient satisfaction. The mean follow-up was 66.3 months (range 60-85). RESULTS: A total of 117 patients in group 1 and 104 patients in group 2 were documented in this study. The subjective and objective cure rates were 87.17%, 64.95% in group 1 and 89.42%, 68.26% in group 2. Patient satisfaction rates (visual analog scale [VAS] score ≥80) were 71.79 and 83.65% in groups 1 and 2 respectively (p = 0.035). Complications were reported according to the Clavien-Dindo classification with grade I 7.7%, grade II 69.2%, grade IIIa 7.7%, and grade IIIb 15.4%, and grade I 9.5%, grade II 47.6%, grade IIIa 42.8%, and grade IIIb 0% in groups 1 and 2 respectively. CONCLUSIONS: Concomitant vaginal prolapse repair with TOT does not have any negative effects on continence outcomes; on the contrary, it increases patient satisfaction.

The Role of Thrombocyte/Lymphocyte Ratio and Aspartate Transaminase/Alanine Transaminase (De Ritis) Ratio in Prediction of Recurrence and Progression in Non-muscle Invasive Bladder Cancer.

AIM: The purpose of the study was to determine the predictive value of platelet-to-lymphocyte ratio (PLR) and Aspartate transaminase (AST)/alanine transaminase (ALT) ratio (De Ritis ratio) for recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). METHODS: A total of 231 patients who underwent transurethral tumor resection between 2016 and 2022 were retrospectively analyzed. Preoperative test results, including AST, ALT, platelet, and lymphocyte counts, were used to calculate the PLR and De Ritis ratio. Univariate and multivariate analyses were performed to identify the predictive factors associated with recurrence and progression. RESULTS: Based on the ROC curve, 1.19 and 1.21 were identified as the optimal cut-off values of the De Ritis ratio for recurrence and progression, respectively. Furthermore, PLR cut-off values for recurrence and progression were 114 and 118, respectively. There is a significant difference in recurrence-free survival (RFS) and progression-free survival (PFS) between the groups of patients with high and low De Ritis ratios (p = 0.028 and p = 0.021, respectively). In multivariate analysis, De Ritis ratio ≥ 1.19 and European Organization for Research and Treatment of Cancer (EORTC) high recurrence risk were determined to be significant predictors of tumor recurrence. Multivariate analysis also determined that T1 pathological stage, high tumor grade, European Organization for Research and Treatment of Cancer (EORTC) high progression risk, and De Ritis ratio ≥ 1.21 were risk factors for tumor progression. CONCLUSION: In our study, the preoperative De Ritis ratio represented an independent predictive factor for recurrence and progression in non-muscle invasive bladder cancer. The use of this biomarker in combination with other diagnostic/predictive tools might help urologists improve the clinical decision-making process in the future.

Effectiveness of osteopathic manipulative applications on hypothalamic-pituitary-adrenal (HPA) axis in youth with major depressive disorder: a randomized double-blind, placebo-controlled trial.

CONTEXT: Osteopathic treatments regulate the neurovegetative system through joint mobilizations and manipulations, and myofascial and craniosacral techniques. Despite the growing body of research, the precise impact of osteopathic medicine on the autonomic nervous system (ANS) is not yet fully elucidated. As to Kuchera's techniques, the stimulation of the sympathetic trunk and prevertebral ganglia contributed to harmonization of the sympathetic activity. However, potential relationships between the harmonization of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis largely remain uncertain and warrant further exploration. OBJECTIVES: This study was designed to evaluate the effectiveness of the osteopathic sympathetic harmonization (OSH) on the SNS and the HPA axis in youth with major depressive disorder (MDD). METHODS: The study included 39 youths aged 15-21 years and diagnosed with MDD. The participants were randomly assigned into either the OSH or the placebo group. Stimulation was performed on the sympathetic truncus and prevertebral ganglia in the OSH group. The stimulation of the placebo group was performed with a lighter touch and a shorter duration in similar areas. Each participant completed the Beck Depression Inventory (BDI) and the State and Trait Anxiety Inventory (SAI and TAI) before the application. Blood pressure (BP) and pulse measurements were made, and saliva samples were taken before, immediately after, and 20 min after application. RESULTS: The baseline BDI (p=0.617) and TAI (p=0.322) scores were similar in both groups. Although the SAI scores decreased in both groups postintervention, no statistically significant difference was found between the two groups. Subjects who received OSH had a decrease in α-amylase level (p=0.028) and an increase in cortisol level (p=0.009) 20 min after the procedure. CONCLUSIONS: Following OSH application in depressed youth, SNS activity may decrease, whereas HPA axis activity may increase. Future studies may examine the therapeutic efficacy of repeated OSH applications in depressed individuals.

Does Second Trimester Maternal Serum Zonulin Level Predict Gestational Diabetes Mellitus?

Zonulin, a protein that regulates intestinal permeability, has attracted attention as a potential biomarker for GDM. Therefore, this study aims to investigate whether there are differences in zonulin levels between the GDM group and control groups, especially between those receiving different treatments (diet and insulin). Based on this idea, we included 90 patients with a gestational age between 24 and 28 weeks in our study. While GDM was not detected in 33 of these patients, as a result of OGTT, 57 patients were diagnosed with GDM and these patients were followed throughout their pregnancy. Gestational diabetes was diagnosed by an OGTT performed between 24 and 28 weeks of gestation according to American Diabetes Association (ADA) standards. During follow-up, GDM patients were divided into two groups according to whether they required insulin treatment. Plasma zonulin levels were determined using enzyme-linked immunosorbent assay (ELISA) techniques. The GDM group had significantly higher plasma zonulin levels than the control group (p < 0.005). According to our research, zonulin may be a non-invasive biomarker involved in the etiology of GDM. Large-scale research on this topic is still needed.

Comparison of two plasma p-tau217 assays to detect and monitor Alzheimer's pathology.

BACKGROUND: Blood-based biomarkers of Alzheimer's disease (AD) have become increasingly important as scalable tools for diagnosis and determining clinical trial eligibility. P-tau217 is the most promising due to its excellent sensitivity and specificity for AD-related pathological changes. METHODS: We compared the performance of two commercially available plasma p-tau217 assays (ALZpath p-tau217 and Janssen p-tau217+) in 294 individuals cross-sectionally. Correlations with amyloid PET and tau PET were assessed, and Receiver Operating Characteristic (ROC) analyses evaluated both p-tau217 assays for identifying AD pathology. FINDINGS: Both plasma p-tau217 assays were strongly associated with amyloid and tau PET. Furthermore, both plasma p-tau217 assays identified individuals with AD vs other neurodegenerative diseases (ALZpath AUC = 0.95; Janssen AUC = 0.96). Additionally, plasma p-tau217 concentrations rose with AD severity and their annual changes correlated with tau PET annual change. INTERPRETATION: Both p-tau217 assays had excellent diagnostic performance for AD. Our study supports the future clinical use of commercially-available assays for p-tau217. FUNDING: This research is supported by the Weston Brain Institute, Canadian Institutes of Health Research (CIHR), Canadian Consortium on Neurodegeneration in Aging, the Alzheimer's Association, Brain Canada Foundation, the Fonds de Recherche du Québec - Santé and the Colin J. Adair Charitable Foundation.