Parkinson disease (PD) pathogenesis remains incompletely understood; beyond nigrostriatal loss, nondopaminergic mechanisms including neurovascular unit dysfunction may contribute to disability. Cerebral small vessel disease (CSVD) burden reflects neurovascular dysfunction in the form of white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), and enlarged perivascular spaces (ePVS). In PD cohorts, CSVD burden correlates with worse motor and gait scores. The aim of the study was to explore whether patients with PD exhibit greater CSVD burden than healthy controls (HC). We conducted a PRISMA-conformant systematic review and meta-analysis of studies including adults with idiopathic PD and a HC group that presented data comparing CSVD burden in these 2 groups. Six databases (MEDLINE, Embase, CINAHL Plus, CENTRAL, Scopus, and Web of Science) were searched on May 14 and 15, 2024. Two reviewers independently screened records, extracted data, and assessed risk of bias, with discrepancies resolved by consensus. Continuous outcomes were pooled as standardized mean differences (SMD); dichotomous outcomes as odds ratios (ORs). We evaluated small-study effects for pooled analyses with 10 or more studies using funnel plots and Egger regression test. We examined 13,403 records. Forty-six studies (45 cross-sectional) met inclusion criteria, totaling 3,817 PD and 2,593 HC (mean ages: 66.9 and 66.5, respectively). WMH volume (k = 21) was higher in PD (SMD 0.36, 95% CI 0.11-0.62). Visual ratings also indicated higher WMH in PD: global (k = 14) SMD 0.27 (95% CI 0.08-0.46); periventricular (k = 11) SMD 0.32 (95% CI 0.12-0.51); deep (k = 8) SMD 0.20 (95% CI 0.09-0.31). Differences in CMB (k = 6; OR 1.18, 95% CI 0.57-2.42) and lacunes (k = 4; OR 1.48, 95% CI 0.58-3.78) were not significant. ePVS results were heterogeneous but trended toward greater burden in PD, most notably in the midbrain (k = 3; SMD 1.80, 0.15-3.44). Overall evidence quality was rated as low, reflecting the observational nature of the included studies. Our analysis showed PD to be associated with greater WMH burden and increased midbrain ePVS. Pooled differences in CMB and lacunes were not significant. Substantial heterogeneity and cross-sectional designs limit certainty; standardized imaging and prospective cohorts are needed to define mechanisms and clinical implications.

To investigate the association between injurious falls and depression and examine the long-term trajectory of injurious falls before, during, and after depression diagnosis. This population-based study analyzed data obtained from two prospective cohorts: the UK Biobank (n=435,662; 2006-2023) and the Swedish Twin Registry (STR; n=43,740; 1998-2016). Injurious fall trajectories were assessed using 16,918 matched pairs from the UK Biobank and 2004 pairs from the STR, where each individual with depression was matched to a depression-free counterpart by birth year and sex. Annual injurious falls and incident depression were observed during follow-up. Multi-adjusted models showed that experiencing an injurious fall at any age was associated with an increased risk of depression in both UK Biobank (hazard ratio [HR]=1.44, 95% confidence interval [CI]=1.31-1.58) and STR (odds ratio [OR]=1.48, 95% CI=1.09-2.02). This association was particularly strong for individuals who fell before age 45 (UK Biobank: HR 1.53 [1.27-1.83]; STR: OR 3.51 [1.95-6.30]) and after age 60 (UK Biobank: HR 1.48 [1.22-1.80]; STR: OR 1.81 [1.03-3.18]). In the STR, injurious fall incidence began rising 3years pre-diagnosis (IRR 1.63 [1.15-2.31]) and gradually declined 6years post-diagnosis (incidence rate ratio [IRR]=1.58, 95% CI=[1.11-2.26]). Injurious falls, especially those occurring before age 45 or after age 60, are associated with a higher risk of subsequent depression. The trajectory of injurious falls among individuals with depression begins increasing three years before diagnosis and peaks in the year of diagnosis.

Metabolic side effects represent a major long-term concern in antipsychotic (AP)-treated early psychosis. We evaluated the weight gain and changes in related metabolic parameters in patients followed up for 12months. We also explored DNA methylation of four genes associated with weight gain (ADRA2A, INSIG2, LEP, MC4R). We included patients aged 15-64years followed in the Ribeirão Preto Early Intervention in Psychosis Program from two different cohorts (Clinical sample, n=147; Epigenetic sample, n=59). DNA methylation was analysed by pyrosequencing only at baseline, after several weeks of AP exposure. In both cohorts, 40% of patients initially received second-generation antipsychotics (SGAs), increasing to over 70% after one year. Clinical sample: At follow-up, patients exhibited significant increases in body mass index (p<0.001), triglycerides (p<0.001), HDL-c (p=0.001) and LDL-c (p<0.001). Patients predominantly on SGAs during the 12months had almost three times higher chance of weight gain than those using haloperidol. Other factors associated with weight gain included non-white skin colour (OR=2.6), fewer years of schooling (OR=2.5) and a weight gain of at least 7% at three months (OR=3.1). Epigenetic sample: Patients receiving SGA treatment (median=23.4weeks) at baseline showed hypermethylation within the MC4R promoter region in relation to patients using haloperidol (median=18.6weeks). No changes in the baseline methylation of other genes related to weight gain or AP drugs were observed longitudinally. MC4R promoter hypermethylation in SGA-treated patients suggests drug-induced metabolic alterations and a potential role of MC4R as a biomarker for predicting AP-related metabolic risk.

This study aimed to assess oncologic outcomes associated with p53 abnormal expression in non-myoinvasive endometrial cancer and contextualize these outcomes by comparison with tumors showing limited (< 50%) myometrial invasion and/or p53 wild-type expression. We retrospectively evaluated patients with uterine-confined endometrial cancer and < 50% myometrial invasion, no cervical invasion, and known p53 status, who underwent complete surgical staging at Mayo Clinic Rochester (1999-2022). All histologic sub-types were included; molecular characterization beyond p53 (including mismatch repair and POLE status) was not systematically available. Adjuvant treatment was administered according to clinicopathological characteristics and institutional practice. Patients' tumors were classified into 4 groups according to p53 status and the presence of myoinvasion: p53 abnormal (p53abn) tumors non-myoinvasive, p53abn tumors with < 50% myoinvasion, p53 wild-type (p53wt) tumors non-myoinvasive, and p53wt with < 50% myoinvasion. Kaplan-Meier curves and log-rank tests were reported for 5-year recurrence-free and overall survival. Univariate and multi-variable Cox proportional hazards models were fitted to identify factors associated with death and recurrence in the overall population. Of the 473 patients, the focus is on 81 patients with p53abn non-myoinvasive endometrial cancer. This group showed an 88.1% (95% confidence interval [CI] 80.5 to 96.3) 5-year recurrence-free survival, with most recurrences being distant (75%). Among patients with p53abn tumors, overall survival did not differ between those with and without myometrial invasion (p53abn non-myoinvasive and p53abn with < 50% myoinvasion pairwise log-rank p =.63), although recurrence-free survival was significantly worse in the p53abn with < 50% myoinvasion group (p53abn non-myoinvasive and p53abn with < 50% myoinvasion pairwise log-rank p =.02). When p53abn non-myoinvasive tumors were compared with p53wt tumors, no differences in overall or recurrence-free survival were observed in pairwise analyses; however, overall survival was significantly shorter for p53abn non-myoinvasive tumors when all p53wt cases were combined (log-rank p =.04), whereas recurrence-free survival remained similar (log-rank p =.59). Abnormal p53 expression was associated with recurrence (hazard ratio [HR] 1.93, 95% CI 1.12 to 3.32) and shorter survival (HR 1.80, 95% CI 1.004 to 3.24), whereas the presence of myometrial invasion was not predictive of either overall or recurrence-free survival. This retrospective study confirms the aggressive nature of p53abn tumors, even in the absence of myometrial invasion, underscoring the importance of molecular assessment in endometrium-confined tumors. These results warrant validation in larger, prospective cohorts.

This review summarizes the most recent evidence evaluating the clinical impact of pulse modulation technologies in endourology, with a specific focus on laser lithotripsy and endoscopic prostate enucleation. Pulse modulation alters laser-fluid-target interaction by influencing cavitation bubble dynamics, optical shielding, and momentum transfer. Advanced pulse-shaping strategies, including split-pulse delivery (e.g. Moses Technology, Virtual Basket), extended vapor-channel pulses, controlled cavitation systems, and very low peak power modulation (e.g. Magneto Technology), have demonstrated improved energy coupling, reduced retropulsion, and enhanced procedural performance in preclinical models. In laser lithotripsy, evidence spans in vitro experiments, prospective cohorts, retrospective comparisons, and one randomized controlled trial. While preclinical data consistently support improved fragmentation efficiency and retropulsion control, clinical studies report comparable stone-free rates between pulse-modulated holmium:yttrium-aluminum-garnet (Ho:YAG), conventional Ho:YAG, and thulium fiber lasers, with modest advantages in operative efficiency and energy consumption. In prostate enucleation, available data are mostly limited to nonrandomized studies, suggesting improved hemostasis and procedural efficiency without clear benefits in functional outcomes. Pulse modulation improves laser handling and efficiency, but its superiority in hard clinical outcomes remains unproven.

Chronic hepatitis B (CHB) affects an estimated 254 million people globally. Historically, WHO and professional society guidelines have recommended treatment for individuals at high risk of disease progression, including those with hepatitis B virus (HBV) DNA concentrations >20 000 IU/mL. Whether individuals at lower risk, including those with HBV DNA <20 000 IU/mL and normal alanine aminotransferase concentrations, benefit from treatment remains uncertain. To inform 2024 WHO guidelines and the potential expansion of treatment threshold recommendations, we conducted two linked systematic reviews and meta-analyses; this analysis examines the incidence of clinical outcomes in untreated adults with non-cirrhotic CHB stratified by baseline HBV DNA and ALT concentrations. In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, and the Cochrane Library for longitudinal prospective and retrospective cohort studies, randomised controlled trials, and non-randomised studies of interventions, published in any language, from Jan 1, 2000, to Feb 6, 2023. We also reviewed the reference lists of included studies and systematic reviews and consulted networks of experts to identify other data sources. Included studies followed up adults (≥18 years) with non-cirrhotic CHB who had no history of antiviral therapy at enrolment, had baseline HBV DNA quantification and ALT measurement, had a follow-up period of at least 48 weeks, and assessed one or more of six key clinical outcomes (hepatocellular carcinoma, cirrhosis, liver-related mortality, all-cause mortality, liver decompensation, and indication for liver transplantation) or six additional outcomes (advanced liver fibrosis, progression of liver fibrosis, becoming eligible for antiviral treatment, hepatitis flare, and HBsAg and HBeAg seroclearance). Outcomes were required to be stratified by HBV DNA concentrations (<200 IU/mL, <2000 IU/mL, 2000-19 999 IU/mL, 20 000-199 999 IU/mL, and ≥200 000 IU/mL) or ALT concentrations (less than the upper limit of normal [ULN], 1·0-1·9 × ULN, and ≥2·0 × ULN). We excluded studies that focused solely on individuals who were pregnant; were co-infected with HIV, hepatitis C virus, or hepatitis D virus; or had another underlying condition other than CHB. We extracted aggregate data and used random-effects meta-analysis to pool incidence rates per 100 person-years. This study was registered with PROSPERO (CRD42023431652). Of 13 231 studies screened, 71 met the inclusion criteria. A concentration-response relationship was observed between single baseline HBV DNA measurements and hepatocellular carcinoma incidence rates per 100 person-years: 0·131 (95% CI 0·097 to 0·177, I2=0%) for HBV DNA concentrations <200 IU/mL, 0·176 (0·117-0·266, I2=88%) for <2000 IU/mL, 0·311 (0·245-0·393, I2=13%) for 2000-19 999 IU/mL, 0·862 (0·725-1·026, I2=0%) for 20 000-199 999 IU/mL, and 0·941 (0·668-1·324, I2=58%) for ≥200 000 IU/mL (p<0·0001 for between-group difference). Similar concentration-response patterns were observed for development of cirrhosis (0·298 [95% CI 0·214-0·415], two studies, for <200 IU/mL; 0·300 [0·146-0·616], I2=88%, for <2000 IU/mL; 0·712 [0·624-0·814], I2=46%, for 2000-19 999 IU/mL; 1·436 [0·991-2·082], I2=76%, for 20 000-199 999 IU/mL; and 2·193 [1·690-2·846], I2=82%, for ≥200 000 IU/mL) and liver-related mortality (0·086 [95% CI 0·054-0·136], one study; 0·083 [0·015-0·451], I2=0%; 0·303 [0·228-0·402], I2=0%; 0·766 [0·591-0·993], one study; and 1·118 [0·951-1·314], two studies), but no concentration-response relationship was observed between a single baseline HBV DNA assessment and all-cause mortality or liver decompensation. Compared with ALT below the ULN, incidence rates of hepatocellular carcinoma, cirrhosis, and liver-related mortality were higher in individuals with baseline ALT concentrations 1·0-1·9 × ULN or ≥2·0 × ULN. A similar pattern was not found for all-cause mortality, and other outcomes were not meta-analysed due to small numbers. Within the HBV DNA strata of <2000 IU/mL, 2000-19 999 IU/mL, and ≥200 000 IU/mL, hepatocellular carcinoma incidence rates were 2-3 times higher in individuals with ALT 1·0-1·9 × ULN than in those with ALT concentrations less than the ULN. Individuals with persistently low HBV DNA concentrations (<2000 IU/mL) or persistently normal ALT concentrations across multiple assessments had slightly lower hepatocellular carcinoma incidence rates compared with those assessed by a single measurement. Our risk of bias assessment found 15 (21%) of 71 studies to be rated as good quality, 40 (56%) as fair quality, and 16 (23%) as poor quality. These findings, alongside the linked systematic review and meta-analysis of antiviral treatment efficacy, supported the 2024 WHO guidelines expansion of treatment criteria to include individuals with HBV DNA concentrations >2000 IU/mL and ALT concentrations above the ULN. For those with HBV DNA concentrations <2000 IU/mL and persistently normal ALT concentrations, treatment can be deferred. WHO.

Maternal adversity and peripheral proinflammatory cytokine concentrations in pregnancy.

Associations of the first trimester exposure to PM2.5 components and offspring atopic dermatitis: Effect modification by systemic low-grade inflammation.

Unsupervised comprehensive CT imaging clusters reveal distinct morphological phenotypes in asthma: insights from two prospective cohorts

The global incidence of thyroid cancer (TC) has increased, with metabolic syndrome (MetS) identified as a potential modifiable risk factor. However, epidemiological evidence regarding this association remains inconsistent. We conducted a meta-analysis to quantify the relationship between MetS and the risk of incident TC in adult populations. We searched PubMed, Embase, and Web of Science for longitudinal observational studies assessing MetS in relation to incident TC. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models to account for heterogeneity. Our analysis included six cohort studies comprising seven independent datasets and a total of 15,730,432 participants, among whom 83,351 incident TC cases were identified during follow-up periods ranging from 2.7 to 12.0 years. The results indicated that MetS was associated with a significantly increased risk of TC (RR = 1.26, 95% CI 1.10–1.46; p &lt; 0.001), exhibiting substantial heterogeneity (I² = 91%). This association was consistent across prospective and retrospective cohorts, varying sample sizes, follow-up durations, and different strata of TC incidence (all p for subgroup differences &gt; 0.05). Moreover, sex-specific analyses revealed comparable associations in both men and women. Studies with higher methodological quality (Newcastle-Ottawa Scale score = 9) demonstrated a diminished yet still significant association compared to those with scores of 7–8 (RR = 1.15 vs. 1.80; p for subgroup difference &lt; 0.001). In conclusion, MetS is associated with a moderately increased risk of TC in adults. However, due to the observational nature of the included studies and the potential for residual confounding, these findings should be interpreted as an association rather than definitive evidence of a causal relationship.

Static body mass index (BMI) measurements overlook longitudinal weight dynamics. We examined the association between time in target range for BMI (TTR-BMI), which integrates stability and target attainment, and incident multimorbidity. We performed a landmark analysis using the English Longitudinal Study of Ageing and China Health and Retirement Longitudinal Study. We included participants aged ≥45 years free of multimorbidity. We calculated TTR-BMI via linear interpolation based on the trapezoidal rule to quantify continuous exposure to a target weight range. We used stratified Cox proportional hazards models to estimate hazard ratios (HRs) for incident multimorbidity. To address proportional hazards violations, we employed time-dependent coefficient analysis to examine temporal heterogeneity (≤3 years vs. >3 years). Lastly, we used negative binomial regression to assess secondary outcomes (disease accumulation). Among 6935 participants, there were 2483 incident cases. Higher TTR-BMI was inversely associated with multimorbidity risk in a dose-response manner. In fully adjusted models, each one standard deviation increase in TTR-BMI reduced risk by 6% (HR = 0.94; 95% confidence interval (CI) = 0.90-0.99). Time-dependent analysis revealed this protection was specific to the late (>3 years) follow-up phase (HR = 0.91; P = 0.003), with no significant effect in the early phase. Furthermore, higher TTR-BMI was associated with a lower rate of disease accumulation (incidence rate ratio = 0.97; 95% CI = 0.95-1.00, P = 0.046). We found that TTR-BMI is an independent predictor of incident multimorbidity. Maintaining a higher TTR-BMI serves as a protective factor against disease onset. Maximising time spent in a healthy weight range offers a precise, longitudinal target for primary prevention in older adults.

Adulthood stressful life events as predictors of incident cardiovascular disease: insights from two prospective cohorts.

ABSTRACT Traumatic brain injury (TBI) remains a major global public health challenge, contributing substantially to morbidity and mortality while imposing a significant socioeconomic burden. In recent years, notable progress has been made in understanding TBI pathophysiology, classification, monitoring, and treatment. Large‐scale randomized controlled trials (RCTs) and longitudinal cohort studies have played a pivotal role in refining clinical guidelines. Concurrently, the development of regional expert consensus statements has enabled treatment strategies to be better tailored to local clinical contexts, thereby optimizing resource utilization and improving therapeutic outcomes. This review highlights global trends and recent advances in TBI management, encompassing innovations in clinical classification systems, neurocritical care, neuroprotective interventions, emerging technologies, and the implementation of precision medicine approaches. Looking forward, the integration of interdisciplinary expertise, personalized treatment strategies, and enhanced global collaboration is expected to elevate standards of care and improve outcomes for patients with TBI.

Background: The early detection of prostate and testicular tumors remains challenging as standard diagnostic tools often lack sensitivity and produce ambiguous results. Seminal fluid is a biologically rich medium that closely reflects the state of male reproductive tissues and has therefore emerged as a promising source of non-invasive molecular biomarkers. Objective: This study aimed to critically evaluate the evidence regarding cell-free DNA, RNA, proteins and metabolites in seminal fluid, and to assess their potential for improving the early detection of male reproductive cancers. Methods: A systematic review was performed according to PRISMA guidelines. Comprehensive searches of the PubMed and Scopus databases were conducted to identify original clinical studies analyzing molecular biomarkers in seminal fluid from patients with prostate or testicular tumors. For each study, data were extracted on biomarker types, cohort characteristics, analytical methods and diagnostic performance. Results: Forty-two eligible studies were included, covering multiple biomarker classes. Most were observational, single-center investigations classified as level 3b evidence. Across the different types of biomarkers, seminal fluid was associated with tumor-associated molecular changes. Alterations in the concentration, fragmentation and methylation patterns of cell-free DNA (e.g., GSTP1, RARβ2, LGALS3 and OCT3/4) distinguished malignant from benign conditions with sensitivities of up to 80–100%. RNA-based markers, including microRNAs, small non-coding RNAs, and tRNA fragments, showed improved performance in several studies, with multimarker models achieving areas under the curve (AUCs) of 0.85–0.93. Proteomic analyses identified high-specificity candidates such as TGM4, AMACR, PROS1 and DKK3. Metabolomic profiling further strengthened the diagnostic potential; reduced seminal citrate outperformed prostate-specific antigen (AUC 0.748 vs. 0.548), and reproducible shifts in amino acid and lipid profiles were observed in testicular tumors. However, substantial heterogeneity in study design, patient selection, and analytical platforms was observed. Risk of bias varied, and large prospective validation cohorts were lacking. Conclusions: Current evidence suggests that seminal fluid contains molecular signals associated with tumors that could be used for diagnosis. However, the available data are predominantly exploratory and methodologically heterogeneous. Before seminal fluid-based biomarkers can be considered for routine clinical implementation, robust prospective studies with standardized protocols are required.

Background/Objectives: Oocyte donation (OD) pregnancies involve complete maternal–fetal genetic disparity and are associated with increased placental dysfunction and adverse perinatal outcomes. However, a unified histopathological framework to characterize alloimmune-mediated placental injury in OD gestations is lacking. This study evaluates immune and vascular alterations in OD triplet placentas and proposes a structured scoring system, the Placental Allograft Rejection-like Score (PARS), to quantify immunovascular dysregulation. Methods: This retrospective study included all OD triplet pregnancies with placental examination performed during 24 years at a tertiary referral center. Maternal, obstetric, fetal, neonatal, and pathological variables were analyzed at the pregnancy level. Histological and immunohistochemical features previously shown to differ between OD and non-OD pregnancies were grouped into six domains: innate immunity, adaptive immunity, checkpoint regulation, vascular remodeling, complement activation, and trophoblastic behavior. Binary thresholds, immunoreactive scores or established morphological cut-offs, were applied to construct a 20-point score classified into three grades. Results: Forty-five OD triplet pregnancies were analyzed. Intra-pregnancy concordance for PARS components was high, with intraclass correlation coefficient ≥0.70 in 87.3% pregnancies. Increasing PARS grades demonstrated a clear clinical gradient. Grade 3 pregnancies had significantly lower birthweight, higher rates of prematurity (&lt;34 weeks), and increased fetal growth restriction. Placental weight decreased progressively with higher PARS. Histologically, grade 3 placentas showed significantly increased accelerated villous maturation and intervillous fibrin deposition. Conclusions: PARS integrates immune and vascular placental lesions into a structured and reproducible framework that correlates with clinically relevant perinatal outcomes and may support future clinical risk stratification, although further validation in larger, multicenter prospective cohorts is required.

The combined impact of social isolation and unhealthy risk score on mortality risk: a study from two prospective cohorts.

Asymptomatic brain lesions (ABLs), including white matter hyperintensities (WMHs), silent brain infarcts (SBIs), and cerebral microbleeds (CMBs), are common MRI markers of cerebral small-vessel disease and predictors of future stroke. However, the optimal blood pressure (BP) target for primary prevention in individuals with ABLs remains unclear. We analyzed 2363 neurologically healthy adults (mean age 61.9 ± 10.9 years; 54% men) who underwent brain MRI screening ("Brain Dock") and were followed for incident stroke over a mean of 8.9 years. ABLs were defined as the presence of SBI, WMH (Fazekas grade ≥ 2), or CMBs. The association between systolic BP (SBP) and stroke risk was evaluated using Cox proportional hazards models with restricted cubic splines, stratified by ABL status, and adjusted for age, sex, HbA1c, LDL-C, and antihypertensive use. The interaction between SBP and the ABL status was not significant. Stroke risk increased progressively with increasing SBP in both groups. In the ABL-positive group, the risk appeared to increase at comparatively lower SBP levels; however, this observation was descriptive and should not be interpreted as indicating a specific threshold. Due to limited stroke events and wide confidence intervals, particularly at higher SBP levels, these spline-based patterns should be considered exploratory rather than definitive. However, confirmation in larger prospective cohorts and interventional studies is needed before MRI-defined cerebrovascular markers can inform clinical blood pressure strategies.

Background: Age-related hearing loss (ARHL) is the most common sensory disorder in older adults and has been identified as a potentially modifiable risk factor for cognitive decline and dementia. Increasing evidence suggests that auditory dysfunction may contribute to adverse cognitive trajectories through multiple interacting pathways. This narrative review examines the mechanisms underlying the association between ARHL and cognitive decline, evaluates the impact of hearing rehabilitation, and discusses future research priorities. Methods: A narrative synthesis of epidemiological, neurobiological, and interventional studies was conducted, with emphasis on longitudinal cohort studies, neuroimaging research, and clinical investigations of hearing aids (HAs) and cochlear implants (CIs). Results: ARHL is consistently associated with accelerated cognitive decline and increased dementia risk. Proposed mechanisms include sensory deprivation-related cortical reorganization, increased cognitive load during effortful listening, shared neuropathological processes, and social disengagement. Neuroimaging studies demonstrate structural and functional alterations in auditory and associative brain regions in individuals with hearing loss. Emerging evidence suggests that HA and CI may improve cognitive performance and potentially attenuate decline, although long-term randomized data remain limited. Conclusions: Current evidence supports ARHL as a clinically relevant and potentially modifiable contributor to cognitive decline. Clarifying causal pathways and optimizing early hearing rehabilitation strategies represent key priorities for future dementia prevention research.

Calcitonin doubling time (CT-DT) is an established prognostic tool in medullary thyroid carcinoma (MTC), yet CT measurement can be affected by analytical variability and assay interference. Procalcitonin (PCT) has shown promise as a complementary biomarker, but data on PCT doubling time (PCT-DT) remain scarce. Longitudinal CT and PCT were measured using Elecsys immunoassays in 25 MTC patients followed for up to 24 months after thyroidectomy. Doubling times were estimated using log-linear regression and a rolling-window approach. Agreement was assessed using Spearman correlation, Bland-Altman analysis, and Cohen's κ across predefined DT categories. CT and PCT kinetics showed clear separation across response categories. In progressive disease, CT-DT and PCT-DT were strongly correlated with minimal systematic bias and substantial categorical agreement (κ = 0.76). Short DT values clustered in structural incomplete responders. PCT-DT closely mirrors CT-DT and may serve as a complementary kinetic marker in the postoperative monitoring of MTC, particularly when CT interpretation is uncertain; however, these findings should be considered exploratory and warrant confirmation in larger prospective cohorts before clinical implementation.

Background: Intracavernosal platelet-rich plasma (PRP) is increasingly used for erectile dysfunction (ED), despite the absence of standardized biological characterization and clear dose definitions. This systematic review evaluates the clinical efficacy of PRP in ED while integrating emerging immune-centric mechanistic evidence. Methods: Following PRISMA 2020 guidelines, randomized controlled trials (RCTs) and prospective studies (2020–2025) investigating intracavernosal PRP in adult men with ED were identified across major databases. Validated outcomes included International Index of Erectile Function (IIEF-EF or IIEF-5), Erection Hardness Score (EHS), Sexual Encounter Profile (SEP), and penile Doppler parameters. Preclinical data were narratively integrated to contextualize biological plausibility. Results: Fourteen clinical studies met the inclusion criteria (six RCTs, eight prospective cohorts). Across most studies, PRP produced clinically relevant within-patient improvements, and three RCTs demonstrated minimal clinically important difference (MCID) responder rates compared with placebo. However, other trials showed comparable improvements in placebo arms, underscoring substantial contextual effects. Safety was consistently favourable. Marked heterogeneity in blood volume processed (10–120 mL), injected PRP volume (3–12 mL), preparation systems, and session protocols precluded cross-study comparability. Critically, no study reported platelet dose, leukocyte subsets, peripheral blood mononuclear cell (PBMNC) content, or red blood cell contamination. Preclinical models consistently demonstrate that PRP restores erectile function through angiogenic, neuroprotective, and immunomodulatory mechanisms, including CXCL5-mediated monocyte recruitment and M1-to-M2 macrophage polarization. Conclusions: Intracavernosal PRP shows promising short-term efficacy signals and a favourable short-term safety profile in mild-to-moderate vasculogenic ED, but current evidence is limited by profound biological and methodological heterogeneity. PRP should be reconsidered as an immune-regenerative intervention requiring dose-defined, composition-defined, and mechanistically informed randomized trials. Interpretation of these findings is constrained by the absence of formal risk-of-bias assessment for non-randomized studies, substantial clinical and biological heterogeneity across trials, and the lack of standardized PRP characterization.