Kyoto Prefectural University

Background and objectives: For patients with prostate cancer (PCa), PSMA PET better diagnose metastases than conventional imaging. In a systematic review and meta-analysis (INPLASY register, 2024311004), we aimed to summarize findings with pretreatment PSMA PET in patients with PCa that was localized according to conventional imaging and summarize how pretreatment PSMA PET had influence on biochemical recurrence (BCR)-free survival and overall survival (OS). Methods: We searched for publications in Pubmed, Google Scholar, ClinicalTrials.gov, and reference lists between 2016 and February 2025. We summarized biochemical recurrence-free survival in Forest plots. Results: Nine publications reported 1908 patients and showed that pretreatment PSMA PET was associated with survival. Three publications reported that pretreatment PSMA PET gave better 3–5-year BCR-free survival than conventional imaging (74% versus 57%). Two publications reported PSMA PET-risk for 389 patients. Those with PSMA PET-low-risk lived 5 years longer often than those with PSMA PET high-risk (84% versus 20%). Conclusions: Pretreatment PSMA PET is widely used in the real world. Pretreatment PSMA PET supports personalized treatment and may explain why pretreatment PSMA PET improved BCR-free survival and OS. It is believed that pretreatment PSMA PET may facilitate future progress in care of patients with high-risk PCa.

ABSTRACTHuman milk (HM) is the optimal source of nutrition for infants. Yet the suitability of HM macronutrient composition, paired with the challenge of regulating HM intake, may deserve some consideration for infants with inherited metabolic disorders (IMDs) requiring restrictive and controlled dietary management. Except for classic galactosemia, HM feeding is expected to be feasible, allowing infants to maintain metabolic stability, while growing and developing optimally. However, information about HM feeding in nonphenylketonuria (PKU) literature is scarce. In this systematic review, 52 studies were included, representing 861 infants (86% PKU) receiving HM after IMD diagnosis (mean duration 4–10 months depending on the IMD). For non‐PKU IMDs (e.g., other amino acidopathies, urea cycle disorders, organic acidemias, fatty acid oxidation disorders), outcomes of HM feeding were available for few infants, except for medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency (n = 48). In PKU, HM feeding combined with phenylalanine‐free formula, led to adequate metabolic control (25 studies), growth (15 studies), and neurodevelopment (10 studies). For other IMDs, more evidence is required, but the limited data suggest that HM feeding is possible, with attentive monitoring and disease‐specific formula supplementation where applicable. In MCAD deficiency, ensuring adequate HM intake is essential, as symptoms were more frequently reported in exclusively breastfed infants. No IMD‐specific articles were found on the relationship between HM feeding and many other outcomes of interest (e.g., immune status or comorbidity risk later in life). With the exception of galactosemia, HM feeding is expected to benefit infants with IMD. More data should be published for IMDs other than PKU.

Objective: To report outcomes from routine clinical practice of liver transplantation (LT) following normothermic liver machine perfusion (NLMP) and compare to LT after static cold storage (SCS). Background: NLMP is emerging as a clinical routine in LT as has recently received renewed attention, however outcomes outside of clinical trials are lacking. Methods: All adult LT between February 2018 and January 2023 were included. Comprehensive viability assessment was applied during NLMP. Outcomes were compared between NLMP and SCS recipients, as well as benchmark and non-benchmark cases. Results: Of the 332 LT included, 174 underwent NLMP and 158 were transplanted following SCS. Sixty-seven organs were accepted and transplanted only under the premise of NLMP. One-year graft survival for SCS and NLMP recipients was 83.8% vs. 81.3% and 93.4% for benchmark cases in the overall cohort. Total preservation time had no influence on graft survival in the NLMP group but was associated with inferior 1-year graft survival in the SCS group. NLMP usage increased significantly over the duration of the study period, as did the median total preservation time. With increasing NLMP use and longer preservation times, nighttime surgery decreased significantly from 41.9% to 4.2%. Conclusions: Prolonged preservation times ease logistics and enable daytime surgery. The possibility of NLMP offers to expand liver transplantation without negatively affecting outcomes.

Diseases of the salivary glands are as common as they are diverse and can have different causes. Clinicians can differentiate salivary gland changes based on chronic systemic diseases, congenital and vascular malformations, and benign and malignant tumors. Acute infectious pathologies can also arise as a result of obstructive pathologies. A large number of diseases with similar clinical presentations have to be differentiated. Due to the improved resolution of ultrasound technology over the last 20 years, it is now used as the first imaging modality to examine salivary gland pathologies. It allows a quick, dynamic, and non-invasive examination of the salivary glands and the soft tissue of the neck. In order to accurately diagnose and treat patients, a very good knowledge of these diseases and their appearance on sonography is required.

Abstract Background HIV viremia has been considered a cardiovascular disease (CVD) risk factor, but many studies have had insufficient data on potential confounders. We explored the association between viremia and CVD after adjusting for established risk factors and analyzed whether consideration of viremia would improve CVD prediction. Methods Adults from RESPOND were followed from the first date with available data until the first of rigorously defined CVD, loss to follow-up, death, or administrative censoring. We first analyzed the associations between 6 measures of viremia (time-updated, before antiretroviral therapy [ART], viremia category, and measures of cumulative viremia) and CVD after adjusting for the variables in the D:A:D CVD score (age, sex/gender, smoking, family history, diabetes, recent abacavir, CD4 count, blood pressure, cholesterol, high-density lipoprotein, cumulative use of stavudine, didanosine, indinavir, lopinavir, and darunavir). We subsequently compared predictive performance with and without viremia in 5-fold internal cross-validation. Results A total of 547 events were observed in 17 497 persons (median follow-up, 6.8 years). Although some viremia variables were associated with CVD in univariable analyses, there were no statistically significant associations after adjusting for potential confounders, neither for measures of current viral load, pre-ART viral load, highest viremia category during ART, nor cumulative viremia (modeled both as total cumulative viremia, cumulative viremia during ART, and recent cumulative viremia). Consistently, none of the viremia variables improved prediction capacity. Conclusions In this large international cohort, HIV viremia was not associated with CVD when adjusting for established risk factors. Our results did not show viremia to be predictive of CVD among people with HIV.

Abstract External quality assessment (EQA) cycles are the smallest complete units within EQA programs that laboratories can use to obtain external assessments of their performance. In each cycle, several samples are distributed to the laboratories registered for participation, and ideally, EQA programs not only cover the examination procedures but also the pre- and post-examination procedures. The properties and concentration range of measurands in individual samples are selected with regard to the intended challenge for the participants so that each sample fulfils its purpose. This aims to ensure the most significant possible information gain in every cycle using the lowest possible number of EQA samples and thus, under economically optimal conditions. Participants examine samples and the results are reported to the EQA provider, who compares them with the target values for individual measurands in every sample. The EQA provider assesses the laboratory performance, and finally communicates the assessment results to the participant. The participants evaluate the outcomes of the assessment of their examination results and can draw conclusions in the case of both failing and passing and, if necessary, define improvement measures. After completion, each cycle is evaluated by the provider so that limitations and weaknesses of the EQA program can be identified and appropriate measures taken, or to confirm its continued suitability and appropriateness.

Abstract This is the first in a series of five papers that detail the role and substantial impact that external quality assessment (EQA) and their providers‘ services play in ensuring in-vitro diagnostic (IVD) performance quality. The aim is to give readers and users of EQA services an insight into the processes in EQA, explain to them what happens before EQA samples are delivered and after examination results are submitted to the provider, how they are assessed, what benefits participants can expect, but also who are stakeholders other than participants and what significance do EQA data and assessment results have for them. This first paper presents the history of EQA, insights into legal, financing and ethical matters, information technology used in EQA, structure and lifecycle of EQA programs, frequency and intensity of challenges, and unique requirements of extra-examination and educational EQA programs.

Abstract Providers of external quality assessment (EQA) programs evaluate data or information obtained and reported by participant laboratories using their routine procedures to examine properties or measurands in samples provided for this purpose. EQA samples must offer participants an equal chance to obtain accurate results, while being designed to provide results in clinically relevant ranges. It is the responsibility of the EQA provider to meet the necessary requirements for homogeneity, stability and some other properties of the EQA items in order to offer participants a fair, reliable and technically interesting EQA experience. Thus, the samples are at the heart and in the centre of EQA and its success depends on their quality. This manuscript describes the requirements for EQA samples and the activities of EQA providers to achieve them.

Abstract External quality assessment (EQA) enhances patient safety through the evaluation of the quality of laboratory-based and point of care testing. Regulatory agencies and accreditation organizations utilize the results and the laboratory’s response to them as part of assessing the laboratory’s fitness to practice. In addition, where EQA samples are commutable and the assigned value has been determined using reference measurement procedures (RMPs), EQA data contributes to the verification of metrological traceability of assays as part of the post-market surveillance of in vitro diagnostic (IVD) medical devices (IVD-MDs). More broadly, the scientific and medical communities use EQA data to demonstrate that medical laboratory examination procedures are fit for clinical purposes, to evaluate common reference intervals, and inclusion of data in clinical databases. Scientific groups, the IVD industry, reference laboratories and National Metrology Institutes can work with EQA providers to identify measurands, which should urgently be supported by the development of reference materials or methods. The ability of health systems to respond effectively to fast-evolving medical challenges, such as the Coronavirus Disease-19 (COVID-19) pandemic, is reliant on EQA to demonstrate confidence in the performance of new laboratory methods and testing services. EQA providers are uniquely positioned to assess the performance of IVD-MDs in addition to individual laboratories and testing sites. Although the primary focus of EQA providers remains the improvement of the performance of individual laboratories, there are many stakeholders who benefit from EQA performance data.

Objectives: To determine whether a closed dressing protocol reduces the surgical site infections (SSI) rate compared to conventional closing techniques. Methods: Patients who underwent lumbar spine surgery at two neurosurgical centers were retrospectively included from June 2015 to December 2019. Data on patients, general risk factors, and surgical risk factors for SSI were collected. Patients were subdivided into two groups: a Closed Protocol where the Dermabond® ± Prineo® dressing system was used, and a Conventional Protocol, namely sutures or staples. Statistical analysis was undertaken to compare the infection rates among the different closure techniques. Results: Altogether, 672 patients were included. In the whole cohort, 157 (23.36%) underwent skin closure with staples, 122 (18.15%) with sutures, 98 (14.58%) with intracutaneous sutures, 78 (11.61%) with Dermabond®, and 217 (32.29%) with Demabond® + Prineo®. The overall infection rate was 2.23% (n = 15). Skin suture had the highest infection rate (4.10%), while the lowest was Dermabond® (1.28%) and Dermabond® + Prineo® (1.4%), though the difference was not significant. Risk factors for SSI included higher BMI (29.46 kg/m2 vs. 26.96 kg/m2, p = 0.044), other sites infection (20.00% vs. 2.38%, p = 0.004), and a higher national nosocomial infections surveillance score (p = 0.003). Conclusions: This study showed that a closed protocol with the use of adhesive dressing with or without mesh had a slight tendency to lower infection rates compared to conventional protocol with sutures or staples, although no statistically significant difference was found between the closure techniques. Larger randomized studies are needed to investigate this potential benefit avoiding selection bias.

ABSTRACTReported tick‐borne‐encephalitis (TBE) cases have been increasing in Western Austria, but no data are available on vaccination‐ and infection‐specific seroprevalence. This study aimed to estimate current TBEV‐seroprevalence in the region and inform prevention programs by comparing anti‐NS1‐based‐incidence rates with reported case numbers and vaccination coverage. Between December 2023 and February 2024, serum samples from 4619 blood donors in Western Austria were collected and analyzed using TBEV‐ and WNV‐IgG‐ELISA assays. Seropositive samples were tested with a TBEV‐anti‐NS1‐IgG‐ELISA to distinguish infections from vaccinations. Borderline samples were retested with serum neutralization and triple‐NS1‐assays. The overall anti‐TBEV‐IgG‐seroprevalence was 80.1% (95%CI 78.9–81.3); 2.7% (95%CI 2.3–3.2) of donors tested positive for anti‐TBEV‐NS1 IgG antibodies, indicating previous infection. The notified incidence rate in Western Austria was 2.7/100 000/year, compared to 136.2/100 000/year based on anti‐TBEV‐NS1‐seropositive donors, denoting a substantial number of unreported cases (mean manifestation index 1.9%). The number of donors with TBEV‐infections varied considerably by district, highlighting potential hotspots for TBEV‐infections. The high anti‐NS1‐based, estimated annual TBE incidence rates show significant differences between districts, highlighting the need for targeted prevention programs. The high rate of undiagnosed TBE cases further suggests that estimated anti‐NS1‐based incidence rates should be considered when defining high‐risk areas.

Aim To determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) among Western Austrian adolescents and its association with arterial stiffness as a marker of early vascular ageing. Methods In the cross-sectional Early Vascular Ageing in the YOUth study, liver fat content was assessed by controlled attenuation parameter (CAP) using signals acquired by FibroScan (Echosense, Paris, France) in 14- to 19-year-old Austrian adolescents. Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV) and cardiovascular risk factors by a face-to-face interview, physical examination, and fasting blood analyses. Linear regression models and one-way analysis of variance were performed to analyze the association between liver fat content, MASLD and cfPWV. Results A total of 1292 study participants (65.2% female) aged 17.2 ± 1.3 years were included. MASLD was detected in 62 (4.8%) adolescents. CAP value showed a significant association with cfPWV in the unadjusted model (p < 0.001) but lost its significant influence in the multivariable model after adjusting for sex, age and cardiovascular risk criteria (increased BMI or waist circumference, impaired glucose metabolism, elevated blood pressure, elevated plasma triglycerides, and decreased HDL cholesterol; p = 0.540). In the analysis of variance, a significant increase in cfPWV was observed in adolescents with any of the five cardiovascular risk criteria for MASLD (p < 0.001), but not with the additional presence of steatotic liver disease (p = 0.291). Conclusion In our adolescent cohort, liver fat content and MASLD were not found to be independent predictors for early vascular ageing. Nevertheless, the determination of liver fat content can be a useful tool to identify adolescents at high risk for cardiovascular disease and metabolic syndrome.

Burtscher J., Hüfner K., Kopp M., Schipplick F., Schobersberger W., Gatterer H.

Abstract: Introduction: The human brain is a highly oxygen-dependent organ. Low environmental oxygen availability (e.g., hypobaric hypoxia at altitude) is a major challenge to the brain and numerous endogenous cellular and systemic hypoxia responses therefore are in place to mitigate hypoxic stress. When the dose of the hypoxic stress surpasses the adaptive capabilities of the brain, cerebral forms of high-altitude illnesses can develop, the prevalence of which increases with the altitude. Hypoxia can also trigger psychotic symptoms. Despite that, the effects of altitude exposures on people with pre-existing mental disorders are surprisingly scarcely investigated. Methods: In this narrative review we summarize the literature on the brain’s responses to hypoxia and put them in the context of somatic high-altitude illnesses and mental consequences of altitude exposure from an interdisciplinary perspective. Results: We identify knowledge gaps with high clinical relevance related to the safety of altitude exposures, particularly for individuals with mental disorders. Conclusions: Taken together, research into the vulnerability of people with neuropsychiatric disorders and the risk of developing mental symptoms in different populations (diseased, healthy, athletes) at altitude is urgently needed to provide appropriate evidence-based counselling and treatment.