Prevalence of obesity and associated health risks in soldiers of the German Armed Forces.

BACKGROUND: Obesity rates are rising in the armed forces of Western democratic countries, impacting military readiness and health. This highlights the need for preventive health risk assessments and countermeasures. METHODS: Using mandatory health examination data from 2018 to 2022, we analyzed the prevalence of obesity, health risks, and associated specific military risk factors (rank and unit) in 43,214 soldiers of the German Armed Forces. Statistical methods included χ2 contingencies and binary logistic regressions. RESULTS: The prevalence of obesity (BMI ≥ 30) was 18.0%. Male soldiers (OR = 3.776) and those with an officer's rank (OR = 1.244) had an increased chance for obesity. Serving in a combat unit reduced the chance of being obese (OR = .886). Considering BMI and waist circumference, 2.4% of the total sample faced extremely high cardiovascular and metabolic health risks, while 11.0% and 11.6% had very high or high health risks, respectively. CONCLUSIONS: Our data underscore the importance of targeting obesity-related health risk factors in soldiers to ensure their well-being and deployment readiness.

Pretest PSA and Restaging PSMA PET/CT Predict Survival in Biochemically Recurrent Prostate Cancer.

BACKGROUND: A biochemical recurrence (BCR) risk model was created based on pretest prostate specific antigen (PSA) and groupings by restaging prostate specific membrane antigen (PSMA) PET/CT. METHODS: A cohort of 1216 BCR patients were analyzed for overall survival (OS) according to the PSA threshold and restaging PSMA PET/CT. A Cox regression analysis of OS was carried out to detect significant clinical characteristics. RESULTS: In the cohort, 271 patients had a pretest PSA of <0.5 ng/mL and 945 patients had higher PSA values. The restaging PSMA PET/CT was positive for 834 patients and negative for 369. Of 1203 patients, 133 (11%) died, including 19 of the 369 (5%) patients without positive sites on the restaging PSMA PET/CT, 82 of the 711 (12%) with 1-5 positive sites, and 32 of the 123 (26%) with >5 positive sites. In the Cox regression analysis, four variables significantly predicted OS: treatment center, International Society of Urologic Pathology (ISUP) grade, pretest PSA threshold, and the grouping of positive sites on the restaging PSMA PET/CT. CONCLUSIONS: The pretest PSA and PSMA PET/CT were important for the OS of the BCR patients. The findings argue for the new BCR risk model and serve as framework for ongoing trials.

The Influence of Hypothyroid Metabolic Status on Blood Coagulation and the Acquired von Willebrand Syndrome.

The intent of this prospective study aimed to identify the influence of hypothyroid metabolic status on the coagulation and fibrinolytic system and association with the acquired von Willebrand syndrome (VWS-ac). We compared 54 patients without substitution therapy after radical thyroidectomy with 58 control subjects without pathological thyroid-stimulating-hormone (TSH)-values. Patients with TSH > 17.5 mU/L over a period of >4 weeks were included. The control-collective was selected based on age and sex to match the patient-collective. The data were collected using laboratory coagulation tests and patient questionnaires; a bleeding score was determined. There were significant differences in the measurement of activated-partial-thromboplastin-time (aPTT/p = 0.009), coagulation-factor VIII (p < 0.001) and von-Willebrand-activity (VWF-ac/p = 0.004) between the patient and control groups. The patient cohort showed an increased aPTT and decreased factor VIII and VWF-ac. 29.7% of the patient-collective compared to 17.2% of the control subjects met the definition of VWS-Ac (p = 0.12). The bleeding score showed significantly more bleeding symptoms in patients with a laboratory constellation of VWS-ac (no family history; p = 0.04). Our results suggest hypocoagulability in hypothyroid patients. Hypothyroidism appears to have a higher incidence of VWS-ac. The increased risk of bleeding complications in hypothyroid patients may be of relevant importance for the outcome, especially in the context of invasive interventions.

Correction: von Eyben et al. A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis. Cancers 2022, 14, 5461.

In the original publication [...].

Analgesic Use in Sports.

BACKGROUND: Consumption of medication to alleviate pain is widespread in Germany. Around 1.9 million men and women take analgesics every day; some 1.6 million persons are addicted to painkillers. Analgesic use is thought also to be common in sports, even in the absence of pain. The aim of this study was to assess the extent of painkiller use among athletes. METHODS: In line with the PRISMA criteria and the modified PICO(S) criteria, a systematic literature review was registered (Openscienceframework, https://doi. org/10.17605/OSF.IO/VQ94D) and carried out in PubMed and SURF. The publications identified (25 survey studies, 12 analyses of doping control forms, 18 reviews) were evaluated in standardized manner using the Newcastle Ottawa Scale (NOS) and AMSTAR (A MeaSurement Tool to Assess systematic Reviews). RESULTS: Analgesic use is widespread in elite sports. The prevalence varies between 2.8% (professional tennis) and 54.2% (professional soccer). Pain medication is also taken prophylactically in the absence of symptoms in some non-elite competitive sports. In the heterogeneous field of amateur sports the data are sparse and there is no reliable evidence of wide-reaching consumption of painkillers. Among endurance athletes, 2.1% of over 50 000 persons stated that they used analgesics at least once each month in connection with sports. CONCLUSION: Analgesic use has become a problem in many areas of professional/ competitive sports, while the consumption of pain medication apparently remains rare in amateur sports. In view of the increasing harmful use of or even addiction to painkillers in society as a whole, there is a need for better education and, above all, restrictions on advertising.

BMI Alterations and Prevalence of Overweight and Obesity Related to Service Duration at the German Armed Forces.

The aim of this study was to assess body mass index (BMI) and the prevalence of overweight and obesity at entry and release of service at the German Armed Forces and related associations to service duration. In a cohort study, 85,076 paired BMI data sets (entry and release of service) of German soldiers (5.4% females) between 2010 to 2022 were analyzed retrospectively to assess BMI alterations and the prevalence of overweight (BMI ≥ 25) and obesity (BMI ≥ 30) after service durations of ≤2 years, 2−5 years, or ≥5 years. Between 2010 and 2022, we observed a trend for BMI increases of about 0.5 kg/m2 (X2 = 27.104, p = 0.007). BMI increases differed significantly (X2 = 7622.858, p < 0.001) after ≤2 years (0.0 kg/m2), after 2−5 years (1.1 kg/m2), and after ≥5 years (2.4 kg/m2) and were correlated to service duration (r = 0.34, p < 0.001). The prevalence of overweight increased from 33.0% to 39.5%. Obesity prevalence increased from 3.7% to 6.3%. The switch to obesity was more pronounced for longer service durations. Although secular trends for BMI increases among soldiers were in line with the general population, service duration was related to BMI increases. Especially, the service time depending on pronounced prevalence of obesity should be a matter of debate leading to counteracting measures at the German Armed Forces.

A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis.

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [68Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with a prescan PSA < 0.5 ng/mL (26%), an intermediate risk group with a prescan PSA > 0.5 ng/mL and a PSMA PET/CT with 1 to 5 positive sites (65%), and a poor risk group with a prescan PSA > 0.5 ng/mL and a PSA PET/CT with > 5 positive sites (9%) (p < 0.0001, log rank test). The poor risk group had a five-year OS > 60%. Adding a BCR risk score by the European Association of Urology did not significantly improve the prediction of OS (p = 0.64). In conclusion, the restaging PSMA PET/CT markedly predicted the 5-year OS. The new risk model for patients with PSA-only relapse requires a restaging PSMA PET/CT for patients with a prescan PSA > 0.5 ng/mL and has a potential use in new trials aiming to improve the outcome for patients with PSA-only recurrence who have polysites prostate cancer detected on PSMA PET/CT.

Predictors for Outcome and Complications Related to Urinary Diversion.

BACKGROUND/AIM: Predictors for complications such as insufficiency of intestinal anastomosis in urinary diversion and other risk factors are not well defined. We aimed to elucidate predictive factors for complications in urinary diversions based on preoperative comorbidities and major complications. A special focus was set on anastomosis insufficiency as a major complication. PATIENTS AND METHODS: Preoperative comorbidities, postoperative complications, duration of hospital stay, and follow-up were analyzed in 317 patients with urinary diversion. The impact of preoperative comorbidities on diversion types was described and quantified as defined by the age-adjusted Charlson Comorbidity Index. RESULTS: Overall, 14.8% of patients showed anastomosis-related complications, most within the ileal conduit group (15.9% in the cohort). Severe complications (Clavien-Dindo Classification Score >IIIa) were found in smokers (p=0.046), and in patients with vascular diseases (p=0.007), a high American Society of Anaesthesiologists (ASA)-score (p=0.047), a R1- (p=0.009), as well as a pN1 (p=0.007) status. CONCLUSION: Several independent predictors for several postoperative complications in urinary diversions were identified, which were independent of the diversion method.

177Lu-PSMA Radioligand Therapy Is Favorable as Third-Line Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

In this systematic review and network meta-analysis (NMA), we aimed to assess the benefits and harms of third-line (L3) treatments in randomized controlled trials (RCTs) of patients with metastatic castration-resistant prostate cancer (mCRPC). Two reviewers searched for publications from 1 January 2006 to 30 June 2021. The review analyzed seven RCTs that included 3958 patients and eight treatments. Treatment with prostate-specific membrane antigen (PSMA)-based radioligand therapy (PRLT) resulted in a 1.3-times-higher rate of median PSA decline ≥50% than treatment with abiraterone, enzalutamide, mitoxantrone, or cabazitaxel (p = 0.00001). The likelihood was 97.6% for PRLT to bring about the best PSA response, out of the examined treatments. PRLT resulted in a 1.1-times-higher six-month rate of median radiographic progression-free survival. Treatment with PRLT in the VISION trial resulted in 1.05-times-higher twelve-month median overall survival than L3 treatment with cabazitaxel in other RCTs. PRLT more often resulted in severe thrombocytopenia and less often in severe leukopenia than did cabazitaxel. In conclusion, for patients with mCRPC, L3 treatment with PRLT is highly effective and safe.

Characterization of activation induced [18]F-FDG uptake in Dendritic Cells.

AIM: Activation of immune cells leads to enhanced glucose uptake that can be visualized by [18]F-Fluorodeoxyglucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT). Dendritic cells (DC) are essential for the function of the adaptive immune system. In contrast to other immune cells metabolic changes leading to an increase of [18]F-FDG uptake are poorly investigated. Here, we analysed the impact of different DC activation pathways on their [18]F-FDG uptake. This effect was then used to radiolabel DC with [18]F-FDG and track their migration in vivo. METHODS: DC were generated from bone marrow progenitors (BMDC) or isolated from spleens (SPDC) of C57BL/6 mice. After stimulation with the TLR ligands LPS and CpG or anti-CD40 antibody for up to 72 hours activation markers and glucose transporters (GLUTs) were measured by flow cytometry. Uptake of [18]F-FDG was measured by gamma-counting. DC lysates were analysed for expression of glycolysis relevant proteins by mass spectrometry (MS). [18]F-FDG-labeled DC were injected into footpads of mice to image DC migration. RESULTS: BMDC and SPDC showed strong upregulation of activation markers predominantly 24 hours after TLR stimulation followed by higher uptake of [18]F-FDG. In line with this, the expression of GLUTs was upregulated during the course of activation. Furthermore, MS analyses of DC lysates revealed differential regulation of glycolysis relevant proteins according to the stimulatory pathway. As a proof of principle, DC were labeled with [18]F-FDG upon activation to follow their migration in vivo via PET/MRI. CONCLUSION: Immune stimulation of DC leads to enhanced [18]F-FDG uptake into DC, representing the typical shift to aerobic glycolysis in immune cells after activation.

The significance of FNAC in diagnosing differentiated thyroid cancer and the discrepancy between theory and practice - a multi-centre study.

INTRODUCTION: After non-invasive diagnostic modalities high risk thyroid nodules are investigated with fine needle aspiration cytology in order to find the right surgical strategy for suspected malignancies. Despite the clear recommendation by the European and the American associations (ETA, ATA) its clinical value is doubted and its importance in clinical practice not fully clarified. METHODS: A multicentric study of 119 patients with differentiated thyroid cancer operated on in 24 surgical departments was conducted. The aim was not only to evaluate the use of FNAC as a diagnostic tool, but also to investigate its diagnostic validity and compare it with that of other, non-invasive diagnostic methods. RESULTS: FNAC was used only in 25 % of malignant thyroid nodules. In these patients sensitivity of FNAC was 60 %. In 40 % with preoperative FNAC, the result had an impact on the surgical approach. 17 % underwent surgery only because of the FNAC result, and 23 % underwent a planned surgical resection with total thyroidectomy and lymphadenectomy on account of the FNAC result. In comparison to non-invasive diagnostics (ultrasonography in conjunction with scintigraphy with Na99mTcO4) FNAC reached the same sensitivity. DISCUSSION: The results of our study reveal a limited application of preoperative FNAC in diagnosing thyroid nodules as well as a limited conclusiveness in our study population if not performed according to standards. In order to increase the benefits of this diagnostic modality, it seems to be important to perform FNAC according to the guidelines and in a standardized manner. FNAC should always be conducted in combination with ultrasonography. An experienced cytopathologist should be consulted and the Bethesda classification system should be established.

PSA and PSA Kinetics Thresholds for the Presence of 68Ga-PSMA-11 PET/CT-Detectable Lesions in Patients With Biochemical Recurrent Prostate Cancer.

68Ga-PSMA-11 positron-emission tomography/computed tomography (PET/CT) is commonly used for restaging recurrent prostate cancer (PC) in European clinical practice. The goal of this study is to determine the optimum time for performing these PET/CT scans in a large cohort of patients by identifying the prostate-specific-antigen (PSA) and PSA kinetics thresholds for detecting and localizing recurrent PC. This retrospective analysis includes 581 patients with biochemical recurrence (BC) by definition. The performance of 68Ga-PSMA-11 PET/CT in relation to the PSA value at the scan time as well as PSA kinetics was assessed by the receiver-operating-characteristic-curve (ROC) generated by plotting sensitivity versus 1-specificity. Malignant prostatic lesions were identified in 77%. For patients that were treated with radical prostatectomy (RP) a PSA value of 1.24 ng/mL was found to be the optimal cutoff level for predicting positive and negative scans, while for patients previously treated with radiotherapy (RT) it was 5.75 ng/mL. In RP-patients with PSA value <1.24 ng/mL, 52% scans were positive, whereas patients with PSA ≥1.24 ng/mL had positive scan results in 87%. RT-patients with PSA <5.75 ng/mL had positive scans in 86% and and for those with PSA ≥5.75 ng/mL 94% had positive scans. This study identifies the PSA and PSA kinetics threshold levels for the presence of 68Ga-PSMA-11 PET/CT-detectable PC-lesions in BC patients.