Case Report: Traumatic cardiac arrest due to pericardial tamponade: successful pericardiocentesis with a Shaldon catheter.

In this report, we describe the successful resuscitation of a 4-year-old child who suffered a traumatic cardiac arrest during a routine procedure in the operating room. The diagnosis of a sanguineous pericardial tamponade was made by emergency ultrasonography. Consecutive subxiphoid pericardiocentesis with an adult Shaldon catheter led to return of spontaneous circulation. Subsequent thoracotomy and surgical suturing definitively stopped the bleeding from the right ventricle. The combined expertise of all perioperative disciplines was decisive for the patient's survival.

Genotype- and sex-specific changes in vital parameters during isoflurane anesthesia in a mouse model of Alzheimer's disease.

Background: The prevalence of neurodegenerative diseases is increasing as is life expectancy with Alzheimer's disease accounting for two-thirds of dementia cases globally. Whether general anesthesia and surgery worsen cognitive decline is still a matter of debate and most likely depending on the interplay of various influencing factors. In order to account for this complexity, Alzheimer's disease animal models have been developed. The Tg2576 model of Alzheimer's disease is a well-established mouse model exhibiting amyloidopathy and age-dependent sex-specific differences in Alzheimer's disease symptomology. Yet, data on anesthesia in this mouse model is scarce and a systematic comparison of vital parameters during anesthesia with wild-type animals is missing. In order to investigate the safety of general anesthesia and changes in vital parameters during general anesthesia in Tg2576 mice, we did a secondary analysis of vital parameters collected during general anesthesia in aged Tg2576 mice. Methods: After governmental approval (General Administration of the Free State of Bavaria, file number: 55.2-1-54-2532-149-11) 60 mice at 10-12 months of age were exposed to isoflurane (1.6 Vol%) for 120 min, data of 58 mice was analyzed. During general anesthesia, heart rate, respiratory rate, temperature, isoflurane concentration and fraction of inspired oxygen were monitored and collected. Data were analyzed using univariate and multivariate linear mixed regression models. Results: During general anesthesia, heart rate decreased in a sex-specific manner. Respiratory rate decreased and body temperature increased dependent on genotype. However, the changes were limited and all vital parameters stayed within physiological limits. Conclusion: Isoflurane anesthesia in the Tg2576 mouse model is safe and does not seem to influence experimental results by interacting with vital parameters. The present study provides information on appropriate anesthesia in order to advance research on anesthesia and AD and could contribute to improving laboratory animal welfare.

ERK signaling promotes resistance to TRK kinase inhibition in NTRK fusion-driven glioma mouse models.

Pediatric-type high-grade gliomas frequently harbor gene fusions involving receptor tyrosine kinase genes, including neurotrophic tyrosine kinase receptor (NTRK) fusions. Clinically, these tumors show high initial response rates to tyrosine kinase inhibition but ultimately recur due to the accumulation of additional resistance-conferring mutations. Here, we developed a series of genetically engineered mouse models of treatment-naïve and -experienced NTRK1/2/3 fusion-driven gliomas. Both the TRK kinase domain and the N-terminal fusion partners influenced tumor histology and aggressiveness. Treatment with TRK kinase inhibitors significantly extended survival of NTRK fusion-driven glioma mice in a fusion- and inhibitor-dependent manner, but tumors ultimately recurred due to the presence of treatment-resistant persister cells. Finally, we show that ERK activation promotes resistance to TRK kinase inhibition and identify MEK inhibition as a potential combination therapy. These models will be invaluable tools for preclinical testing of novel inhibitors and to study the cellular responses of NTRK fusion-driven gliomas to therapy.

Goal-directed Perioperative Albumin Substitution Versus Standard of Care to Reduce Postoperative Complications: A Randomized Clinical Trial (SuperAdd Trial).

OBJECTIVE: To investigate whether goal-directed albumin substitution during surgery and postanesthesia care to maintain a serum albumin concentration >30 g/L can reduce postoperative complications. BACKGROUND: Hypoalbuminemia is associated with numerous postoperative complications. Since albumin has important physiological functions, substitution of patients with hypoalbuminemia is worth considering. METHODS: We conducted a single-center, randomized, controlled, outcome assessor-blinded clinical trial in adult patients, American Society of Anesthesiologists physical status classification 3 to 4 or undergoing high-risk surgery. Patients, whose serum albumin concentration dropped <30 g/L were randomly assigned to goal-directed albumin substitution maintaining serum concentration >30 g/L or to standard care until discharge from the postanesthesia intermediate care unit. Standard of care allowed albumin substitution in hemodynamic instable patients with serum concentration <20 g/L, only. Primary outcome was the incidence of postoperative complications ≥2 according to the Clavien-Dindo Classification in at least 1 of 9 domains (pulmonary, infectious, cardiovascular, neurological, renal, gastrointestinal, wound, pain, and hematological) until postoperative day 15. RESULTS: Of 2509 included patients, 600 (23.9%) developed serum albumin concentrations <30 g/L. Human albumin 60 g (40-80 g) was substituted to 299 (99.7%) patients in the intervention group and to 54 (18.0%) in the standard care group. At least 1 postoperative complication classified as Clavien-Dindo Classification ≥2 occurred in 254 of 300 patients (84.7%) in the intervention group and in 262 of 300 (87.3%) in the standard treatment group (risk difference -2.7%, 95% CI, -8.3% to 2.9%). CONCLUSION: Maintaining serum albumin concentration of >30 g/L perioperatively cannot generally be recommended in high-risk noncardiac surgery patients.

Wearable in-ear pulse oximetry validly measures oxygen saturation between 70% and 100%: A prospective agreement study.

Objectives: Postoperative monitoring outside intensive and post-anaesthesia care units is seldom, partly due to lack of suitable and approved systems. We therefore aim to validate the oxygen saturation (SpO2) and pulse rate measurement of the in-ear sensor c-med° alpha with a reference pulse oximeter. Methods: This prospective agreement study was conducted in 12 healthy (ASA 1) adult (18-50 years) volunteers according to the EN ISO 80601-2-61. The sitting volunteers were equipped with the finger pulse oximeter Rad-5 and two c-med° alpha sensors in each ear. The inspiratory oxygen content was reduced via a tight-fitting breathing mask to achieve five defined plateaus with stable SpO2 between 99% and 70%. The deviation of the SpO2 and pulse rate measurements of the c-med° alpha from those of the Rad-5 was calculated using the mean square error (Arms). Bias and limits of agreement between both devices were calculated using the Bland-Altman technique. The precision was compared based on the repeatability coefficients. Results: The c-med° alpha measured SpO2 had an Arms = 1.9% relative to the Rad-5, a non-significant bias (-0.1% (-0.2% to 0.0%)), levels of agreement from -4.0% to 3.8%, and the same repeatability coefficient (0.8% vs. 0.8%). The c-med° alpha measured pulse rate did not deviate from the one measured with the certified finger pulse oximeter (bias: 0.1 min-1 (0 to 0.1 min-1), level of agreement: -3.6 to 3.7 min-1, Arms: 1.8 min-1). Conclusions: The c-med° alpha fulfils the EN ISO 80601-2-61 standard and is sufficiently accurate for measuring SpO2 and pulse rate in healthy adults at rest. Trial registration: EUDAMED No. CIV-21-03-036033.

Medical experience as an influencing parameter in emergency medical care for psychiatric emergencies: retrospective analysis of a multicenter survey.

BACKGROUND: Prehospital care of psychiatric patients often relies on the medical experience of prehospital emergency physicians (PHEPs). The psychiatrists (PSs) involved in the further treatment of psychiatric patients also often rely on their experience. Furthermore, the interaction between PHEPs and PSs is characterized by interaction problems and different approaches in the prehospital care of the psychiatric emergency. OBJECTIVES: To analyze the phenomenon of "medical experience" as a cause of possible interaction-related problems and assess its impact on the prehospital decision-making process between prehospital emergency physicians and psychiatrists. METHODS: The retrospective data analysis was conducted between November 2022 and March 2023. Medical experience was defined as follows, based on the demographic information collected in the questionnaires: For PHEPs, the period since obtaining the additional qualification in emergency medicine was defined as a surrogate marker of medical experience: (i) inexperienced: < 1 year, (ii) experienced: 1-5 years, (iii) very experienced: > 5 years. For PSs, age in years was used as a surrogate parameter of medical experience: (i) inexperienced: 25-35 years, (ii) experienced: 35-45 years, (iii) very experienced: > 45 years. RESULTS: Inexperienced PSs most frequently expressed anxiety about the psychiatric emergency referred by a PHEP (27.9%). Experienced PHEPs most frequently reported a lack of qualifications in handling the care of psychiatric emergencies (p = 0.002). Very experienced PHEPs were significantly more likely to have a referral refused by the acute psychiatric hospital if an inexperienced PS was on duty (p = 0.01). Experienced PHEPs apply an intravenous hypnotic significantly more often (almost 15%) than PSs of all experience levels (p = 0.001). In addition, very experienced PHEPs sought prehospital phone contact with acute psychiatry significantly more often (p = 0.01). CONCLUSION: PHEPs should be aware that the PS on duty may be inexperienced and that treating emergency patients may cause him/her anxiety. On the other hand, PHEPs should be receptive to feedback from PS who have identified a qualification deficiency in them. Jointly developed, individualized emergency plans could lead to better prehospital care for psychiatric emergency patients. Further training in the prehospital management of psychiatric disorders is needed to minimize the existing skills gap among PHEPs in the management of psychiatric disorders.

Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema.

Human malignant brain tumors such as gliomas are devastating due to the induction of cerebral edema and neurodegeneration. A major contributor to glioma-induced neurodegeneration has been identified as glutamate. Glutamate promotes cell growth and proliferation in variety of tumor types. Intriguently, glutamate is also an excitatory neurotransmitter and evokes neuronal cell death at high concentrations. Even though glutamate signaling at the receptor and its downstream effectors has been extensively investigated at the molecular level, there has been little insight into how glutamate enters the tumor microenvironment and impacts on metabolic equilibration until recently. Surprisingly, the 12 transmembrane spanning tranporter xCT (SLC7A11) appeared to be a major player in this process, mediating glutamate secretion and ferroptosis. Also, PPARγ is associated with ferroptosis in neurodegeneration, thereby destroying neurons and causing brain swelling. Although these data are intriguing, tumor-associated edema has so far been quoted as of vasogenic origin. Hence, glutamate and PPARγ biology in the process of glioma-induced brain swelling is conceptually challenging. By inhibiting xCT transporter or AMPA receptors in vivo, brain swelling and peritumoral alterations can be mitigated. This review sheds light on the role of glutamate in brain tumors presenting the conceptual challenge that xCT disruption causes ferroptosis activation in malignant brain tumors. Thus, interfering with glutamate takes center stage in forming the basis of a metabolic equilibration approach.

Successful treatment of out-of-hospital cardiac arrest is still based on quick activation of the chain of survival.

Background and goal of study: Cardiopulmonary resuscitation (CPR) in prehospital care is a major reason for emergency medical service (EMS) dispatches. CPR outcome depends on various factors, such as bystander CPR and initial heart rhythm. Our aim was to investigate whether short-term outcomes such as the return of spontaneous circulation (ROSC) and hospital admission with spontaneous circulation differ depending on the location of the out-of-hospital cardiac arrest (OHCA). In addition, we assessed further aspects of CPR performance. Materials and methods: In this monocentric retrospective study, protocols of a prehospital physician-staffed EMS located in Munich, Germany, were evaluated using the Mann-Whitney U-test, chi-square test, and a multifactor logistic regression model. Results and discussion: Of the 12,073 cases between 1 January 2014 and 31 December 2017, 723 EMS responses with OHCA were analyzed. In 393 of these cases, CPR was performed. The incidence of ROSC did not differ between public and non-public spaces (p = 0.4), but patients with OHCA in public spaces were more often admitted to the hospital with spontaneous circulation (p = 0.011). Shockable initial rhythm was not different between locations (p = 0.2), but defibrillation was performed significantly more often in public places (p < 0.001). Multivariate analyses showed that hospital admission with spontaneous circulation was more likely in patients with shockable initial heart rhythm (p < 0.001) and if CPR was started by an emergency physician (p = 0.006). Conclusion: The location of OHCA did not seem to affect the incidence of ROSC, although patients in public spaces had a higher chance to be admitted to the hospital with spontaneous circulation. Shockable initial heart rhythm, defibrillation, and the start of resuscitative efforts by an emergency physician were associated with higher chances of hospital admission with spontaneous circulation. Bystander CPR and bystander use of automated external defibrillators were low overall, emphasizing the importance of bystander education and training in order to enhance the chain of survival.

Association of immature platelets with perioperative complications in neurosurgery.

Immature platelets are newly formed platelets with an increased prothrombotic potential. This study evaluates whether immature platelets are associated with relevant complications in neurosurgical patients. Data were obtained in the frame of a prospectively conducted observational study exploring the association between immature platelets and major cardiovascular events after surgery. Immature platelet fraction (IPF) and H-IPF (highly fluorescent immature platelet fraction) were measured preoperatively and postoperatively at the neurosurgical ward (24-72 hours after surgery). Therapy-relevant complications after surgery were stratified using the Clavien-Dindo Grade (CDG >2) as primary outcome. Data were analyzed in 391 neurosurgical patients. While preoperatively there were no differences in IPF or H-IPF, patients with higher therapy-complication grades had higher values post-op compared to patients with lower grade complications (≤2 CDG). Cut-off values identified by receiver operating characteristic curve analysis revealed that there were significantly more patients with H-IPF ≥0.95% in the group with serious complications (CDG >2) [odds ratio OR (95% confidence interval CI) = 2.06 (1.09-3.9), p = .025], whereas this association was not present for the IPF cutoff value. In a multivariate model, H-IPF≥0.95% was independently associated with serious complications after surgery [OR (95% CI) = 1.97 (1.03-3.78), p = .041]. These findings suggest that H-IPF is associated with surgical complications and may improve risk stratification of neurosurgical patients (clinicaltrials.gov: NCT02097602, registration date: 27/03/2014).

What is the context?Immature platelets are newly formed platelets with a higher thrombotic potential and play an important role in atherothrombotic events.Higher levels of immature platelets were observed in patients with acute coronary syndrome or stroke.Lately, the focus in immature platelet research shifted from observation to outcomes. Immature platelets were identified as independent predictors of major cardiovascular events in cardiologic patients with coronary artery disease. Besides, an association between immature platelets and major cardiovascular events was described in surgical patients after non-cardiac surgery.What is new?This study builds on these findings and extends the focus to perioperative complications after neurosurgery.The data were obtained prospectively in the frame of an observational clinical trial exploring the association of immature platelets and major cardiovascular events in general. Data measured in the neurosurgical cohort of that study (391 neurosurgical patients) were analyzed in the present work.Within the limitations of our study, our analyses suggest that the postoperative IPF (immature platelet fraction) and H-IPF (highly fluorescent immature platelet fraction) values, which were measured at the neurosurgical ward after surgery are both associated with higher therapy-relevant complication grades (>2 according to Clavien-Dindo Grade), whereas preoperatively obtained values were not.What is the impact?This is the first study showing a relationship between immature platelets and therapy-relevant perioperative complications in neurosurgical patients. It could be a pilot trial for varied scientific questions including risk stratification of neurosurgical patients.

Combination of radiation and immunotherapy in the treatment of genitourinary malignancies: A systematic review and meta-analysis.

BACKGROUND: Due to possible synergistic effects, the combination of radiation therapy (RT) and immune checkpoint inhibitors (ICI) represents an interesting therapeutic option. An increasing number of clinical trials are ongoing to investigate this combination in genitourinary malignancies and the first results are available. OBJECTIVES: To review and summarize available data on the combination of RT and ICI in genitourinary malignancies and update the evidence for this potential therapeutic approach. EVIDENCE ACQUISITION: A study protocol was registered in the PROSPERO-Database. Terms of search were prostate cancer, bladder cancer, renal cell carcinoma, penile cancer, testicular cancer, radiotherapy, and immunotherapy in multiple literature databases and study registers. Clinical studies reporting on the combination treatment of RT and ICI were included. A systematic review of ongoing trials according to the PRISMA statement and a meta-analysis of available trials were performed. EVIDENCE SYNTHESIS: Overall, 43 studies met the inclusion criteria examining the therapeutic effect of combined RT and ICI. For bladder cancer, renal cell carcinoma, prostate cancer, and penile cancer 28, 9, 5, and 1 trial could be identified, respectively. No study was found for testicular cancer. Three phases III trials were identified, all other trials were phase I or II. Twelve studies have been completed so far. The meta-analysis of available data indicates comparable toxicity of RT plus ICI vs. ICI alone for grade 3/4 AEs. Mature efficacy data is limited with interesting early results. CONCLUSION: This article reviews the clinical trial landscape investigating RT and ICI in genitourinary malignancies. It provides an overview of ongoing trials and discusses available results. Actual data regarding efficacy is limited, while toxicities seem comparable to ICI alone. Especially in bladder and kidney cancer, further trial results might impact on the clinical use of the combination therapy.

Isoflurane has no effect on cognitive or behavioral performance in a mouse model of early-stage Alzheimer's disease.

Background: Patients with Alzheimer's disease show a sex-dependent decline of cognitive and behavioral performance. It is controversially discussed whether general anesthesia itself can aggravate or even cause this neurocognitive decline. Therefore, we investigated the effect of general anesthesia on neurocognitive and behavioral function and amyloidopathy in a mouse model of early-stage Alzheimer's disease with respect to sex. Methods: After governmental approval 10 months old Tg2576 mice and wild type (total 85 mice) either underwent general anesthesia with 1.0 minimal alveolar concentration of isoflurane for 2 h or were not exposed to isoflurane (controls). Following cognitive and behavioral testing using the modified hole board test (mHBT), brains were investigated regarding amyloidopathy, inflammation, and apoptosis. Data were analyzed using repeated measure analysis of variance (ANOVA) and univariate analysis of variance (UNIANOVA). Results: Tg2576 mice showed a decline in memory function (p < 0.001), less anxiety (p = 0.022 and p = 0.024), increased locomotor activity (p = 0.025), and impaired fine motor skills (p < 0.001). Amyloid precursor protein (p < 0.001), soluble amyloid-beta (p < 0.001) and insoluble amyloid deposits (p < 0.001) were increased in Tg2576 animals. Neither sex nor exposure to isoflurane had an effect on cognitive or behavioral testing or expression of amyloid-related biomarkers. Discussion and conclusion: We found that 10 months old Tg2576 showed typical signs of early-stage Alzheimer's disease and corresponding histopathological alterations. Relevant sex-specific differences or an effect of isoflurane anesthesia could not be detected at this early stage of the disease.

Pathological Reporting of Radical Prostatectomy Specimens Following ICCR Recommendation: Impact of Electronic Reporting Tool Implementation on Quality and Interdisciplinary Communication in a Large University Hospital.

Prostate cancer represents one of the most common malignant tumors in male patients in Germany. The pathological reporting of radical prostatectomy specimens following a structured process constitutes an excellent prototype for the introduction of software-based standardized structured reporting in pathology. This can lead to reports of higher quality and could create a fundamental improvement for future AI applications. A software-based reporting template was used to generate standardized structured pathological reports of radical prostatectomy specimens of patients treated at the University Hospital Klinikum rechts der Isar of Technische Universität München, Germany. Narrative reports (NR) and standardized structured reports (SSR) were analyzed with regard to completeness, and clinicians' satisfaction with each report type was evaluated. SSR show considerably higher completeness than NR. A total of 10 categories out of 32 were significantly more complete in SSR than in NR (p < 0.05). Clinicians awarded overall high scores in NR and SSR reports. One rater acknowledged a significantly higher level of clarity and time saving when comparing SSR to NR. Our findings highlight that the standardized structured reporting of radical prostatectomy specimens, qualifying as level 5 reports, significantly increases objectively measured content quality and the level of completeness. The implementation of nationwide SSR in Germany, particularly in oncologic pathology, can serve pathologists, clinicians, and patients.

The absence of dominant alpha-oscillatory EEG activity during emergence from delta-dominant anesthesia predicts neurocognitive impairment- results from a prospective observational trial.

STUDY OBJECTIVE: Postoperative neurocognitive disorders (PND) are common complications after surgery under general anesthesia. In our aging society the incidence of PND will increase. Hence, interdisciplinary efforts should be taken to minimize the occurrence of PND. Electroencephalographic (EEG) monitoring of brain activity during anesthesia or emergence from anesthesia is a promising tool to identify patients at risk. We therefore investigated whether we could identify specific EEG signatures during emergence of anesthesia that are associated with the occurrence of PND. DESIGN AND PATIENTS: We performed a prospective observational investigation on 116 patients to evaluate the EEG features during emergence from general anesthesia dominated by slow delta waves in patients with and without delirium in the postoperative care unit (PACU-D) as assessed by the CAM-ICU and the RASS. MAIN RESULTS: During emergence both the frontal and global EEG of patients with PACU-D were significantly different from patients without PACU-D. PACU-D patients had lower relative alpha power and reduced fronto-parietal alpha coherence. CONCLUSIONS: With our analysis we show differences in EEG features associated with anesthesia emergence in patients with and without PACU-D. Frontal and global EEG alpha-band features could help to identify patients with PACU-D. CLINICAL TRIAL NUMBER: NCT03287401.

Perioperative Hemodynamic Optimization in Patients at Risk for Delirium - A Randomized-Controlled Trial.

Background: Post-operative delirium is common in elderly patients and associated with increased morbidity and mortality. We evaluated in this pilot study whether a perioperative goal-directed hemodynamic optimization algorithm improves cerebral oxygenation and can reduce the incidence of delirium. Materials and Methods: Patients older than 70 years with high risk for post-operative delirium undergoing elective non-cardiac surgery were randomized to an intervention or control group. Patients in the intervention group received a perioperative hemodynamic optimization protocol based on uncalibrated pulse-contour analysis. Patients in the control group were managed according to usual standard of care. Incidence of delirium until day seven was assessed with confusion assessment method (CAM) and chart review. Cerebral oxygenation was measured with near-infrared spectroscopy. Results: Delirium was present in 13 of 85 (15%) patients in the intervention group and 18 of 87 (21%) in the control group [risk difference -5.4%; 95% confidence interval, -16.8 to 6.1%; P = 0.47]. Intervention did not influence length of stay in hospital or in-hospital mortality. Amounts of fluids and vasopressors applied, mean arterial pressure, cardiac index, and near-infrared spectroscopy values were comparable between groups. Conclusion: The hemodynamic algorithm applied in high-risk non-cardiac surgery patients did not change hemodynamic interventions, did not improve patient hemodynamics, and failed to increase cerebral oxygenation. An effect on the incidence of post-operative delirium could not be observed. Clinical Trial Registration: [Clinicaltrials.gov], identifier [NCT01827501].

International comparison of glycaemic control in people with type 1 diabetes: an update and extension.

AIMS: To update and extend a previous cross-sectional international comparison of glycaemic control in people with type 1 diabetes. METHODS: Data were obtained for 520,392 children and adults with type 1 diabetes from 17 population and five clinic-based data sources in countries or regions between 2016 and 2020. Median HbA1c (IQR) and proportions of individuals with HbA1c < 58 mmol/mol (<7.5%), 58-74 mmol/mol (7.5-8.9%) and ≥75 mmol/mol (≥9.0%) were compared between populations for individuals aged <15, 15-24 and ≥25 years. Logistic regression was used to estimate the odds ratio (OR) of HbA1c < 58 mmol/mol (<7.5%) relative to ≥58 mmol/mol (≥7.5%), stratified and adjusted for sex, age and data source. Where possible, changes in the proportion of individuals in each HbA1c category compared to previous estimates were calculated. RESULTS: Median HbA1c varied from 55 to 79 mmol/mol (7.2 to 9.4%) across data sources and age groups so a pooled estimate was deemed inappropriate. OR (95% CI) for HbA1c < 58 mmol/mol (<7.5%) were 0.91 (0.90-0.92) for women compared to men, 1.68 (1.65-1.71) for people aged <15 years and 0.81 (0.79-0.82) aged15-24 years compared to those aged ≥25 years. Differences between populations persisted after adjusting for sex, age and data source. In general, compared to our previous analysis, the proportion of people with an HbA1c  < 58 mmol/l (<7.5%) increased and proportions of people with HbA1c ≥ 75 mmol/mol (≥9.0%) decreased. CONCLUSIONS: Glycaemic control of type 1 diabetes continues to vary substantially between age groups and data sources. While some improvement over time has been observed, glycaemic control remains sub-optimal for most people with Type 1 diabetes.

Evaluation of Pre-operative Biopsy, Surgical Procedures and Oncologic Outcomes in Upper Tract Urothelial Carcinoma (UTUC).

Purpose: Discordance between pre-operative biopsy and final pathology for Upper Tract Urothelial Carcinoma (UTUC) is high and optimal management remains controversial. The aim of this study is to evaluate the accuracy of pre-operative biopsy, to identify prognostic factors and to evaluate the effect of adjuvant chemotherapy on survival and oncologic outcome in UTUC. Methods: We analyzed records of patients receiving surgical treatment for UTUC. Pathology of pre-operative biopsy was compared to surgical specimen. We used Kaplan-Meier method to estimate survival probabilities and Cox's proportional hazards models to estimate the association between covariates and event times. Primary endpoint was overall survival (OS). A matched-pair analysis was performed to evaluate the effect of adjuvant chemotherapy. Results: 151 patients underwent surgical treatment (28% open, 36% laparoscopic, 17% robotic radical nephroureterectomy; 14% segmental ureteral resections and 5% palliative nephrectomy) for UTUC and were included in the analysis. Upstaging from

Resection of Non-Functional Pancreatic Neuroendocrine Neoplasms-A Single-Center Retrospective Outcome Analysis.

Surgery remains the only curative treatment of pancreatic neuroendocrine neoplasms (pNEN). Here, we report the outcome after surgery for non-functional pNEN at a European Neuroendocrine Tumor Society (ENETS) center in Germany between 2000 and 2019; cases were analyzed for surgical (Clavien-Dindo classification; CDc) and oncological outcomes. Forty-nine patients (tumor grading G1 n = 25, G2 n = 22, G3 n = 2), with a median age of 56 years, were included. Severe complications (CDc ≥ grade 3b) occurred in 11 patients (22.4%) and type B/C pancreatic fistulas (POPFs) occurred in 5 patients (10.2%); in-hospital mortality was 2% (n = 1). Six of seven patients with tumor recurrence (14.3%) had G2 tumors in the pancreatic body/tail. The median survival was 5.7 years (68 months; [1-228 months]). Neither the occurrence (p = 0.683) nor the severity of complications had an influence on the relapse behavior (p = 0.086). This also applied for a POPF (≥B, p = 0.609). G2 pNEN patients (n = 22) with and without tumor recurrence had similar median tumor sizes (4 cm and 3.9 cm, respectively). Five of the six relapsed G2 patients (83.3%) had tumor-positive lymph nodes (N+); all G2 pNEN patients with recurrence had initially been treated with distal pancreatic resection. Pancreatic resections for pNEN are safe but associated with relevant postoperative morbidity. Future studies are needed to evaluate suitable resection strategies for G2 pNEN.

Immune-checkpoint inhibitor-associated diabetes compared to other diabetes types - A prospective, matched control study.

BACKGROUND: To describe checkpoint inhibitor-induced diabetes mellitus (CPI-DM) and to compare with regular type 1 (T1DM), type 2 (T2DM), and medication-induced diabetes mellitus (MI-DM). METHODS: We included 88 177 adult patients from the Diabetes Patient Follow-Up (DPV) registry with diabetes manifestation between 2011 and 2020. Inclusion criteria were T1DM, T2DM, MI-DM, or CPI-DM. Because of the heterogeneity between the groups, we matched patients by age, sex, and diabetes duration using propensity scores. Patient data were aggregated in the respective first documented treatment year. RESULTS: The matched cohort consisted of 24 164 patients; T1DM: 29, T2DM: 24000, MI-DM: 120, CPI-DM: 15 patients. Median age at manifestation of CPI-DM patients was 63.6 (57.2-72.8) years (53.3% male). Body mass index in CPI-DM patients was significantly lower (26.8 [23.9-28.1] kg/m2 ) compared with T2DM patients (29.8 [26.2-34.3] kg/m2 , P = 0.02). At manifestation, HbA1c was significantly higher in CPI-DM compared with MI-DM, but there was no difference during follow-up. Diabetic ketoacidosis (DKA) was documented in six CPI-DM patients (T1DM: 0%, T2DM: 0.4%, MI-DM: 0.0%). Fourteen CPI-DM patients were treated with insulin, and three received additional oral antidiabetics. The most common therapy in T2DM was lifestyle modification (38.8%), insulin in MI-DM (52.5%). Concomitant autoimmune thyroid disease was present in four CPI-DM patients (T1DM: 0.0%, T2DM: 1.0%, MI-DM: 0.8%). CONCLUSIONS: The data from this controlled study show that CPI-DM is characterized by a high prevalence of DKA, autoimmune comorbidity, and metabolic decompensation at onset. Structured diagnostic monitoring is warranted to prevent DKA and other acute endocrine complications in CPI-treated patients.