A pilot study to evaluate the combination of surgery and brachytherapy for local tumor control in young children with perianal rhabdomyosarcoma.

Background: Perianal rhabdomyosarcoma ((P)RMS) are rare and have a poor prognosis. Data in young children are limited and local therapy is not well defined. Combined brachytherapy and surgery is routinely being used for RMS at other sites in children as it provides good oncologic outcomes and allows for organ-sparing surgery. The objective of this study was to evaluate this combination treatment for local tumor control and organ-sparing surgery in young children with (P)RMS. Methods: A retrospective review of the medical records of all children who underwent surgery and brachytherapy for (P)RMS at our institution since 2009 was conducted. Results: Surgery for (P)RMS was performed in 6 patients at a median age of 19 months (range 8-50). Embryonal RMS was diagnosed in 4 patients and alveolar RMS in 2 patients, of which 1 patient had FOXO1 fusion-positive RMS. All patients underwent postoperative high-dose rate (HDR) brachytherapy. Organ-preserving surgery was achieved in 5 of 6 patients (83 %). In 1 patient, the entire sphincter was infiltrated, making organ-preserving resection impossible. 5 of 6 patients (83 %) exhibited an event-free and overall survival at a median follow-up of 26 months (range 8-107). One patient died due to locoregional recurrence. Complications were urethral leakage in 1 patient followed by urethral stenosis and delayed wound healing and vaginal stenosis in another patient. No patient reported fecal incontinence. Conclusions: Combined treatment with surgery and HDR brachytherapy is feasible in very young children with (P)RMS and leads to a favorable oncologic outcome. Preliminary data show a good functional preservation.

Scanning Acousto-Optoelectric Spectroscopy on a Transition Metal Dichalcogenide Monolayer.

The charge carrier dynamics are investigated by surface acoustic waves (SAWs) inside a WSe2 monolayer on LiNbO3 by scanning acousto-optoelectric spectroscopy. A strong enhancement of the PL emission intensity is observed almost over the entire area of the flake. This enhancement increases with increasing amplitude of the wave and is especially strong at or in the vicinity to defects. The latter is attributed to the SAW-driven Poole-Frenkel activation of trapped charge carriers bound to trapping sites at these defects. In addition, the PL intensity exhibit clear periodic modulations at the SAW's frequency fSAW and at 2 fSAW. These modulations are clear and unambiguous fingerprints of spatio-temporal carrier dynamics driven by the SAW. These occur on sub-nanosecond timescales which are found in good agreement with calculated exciton dissociation times. Mapping and analyzing both effects, this study shows that scanning acousto-electric spectroscopy provides a highly sensitive and local contact-free probe which uncovers distinct local features not resolved by conventional quasi-static photoluminescence techniques. The method is ideally suited to study carrier transport in 2D and other types of nanoscale materials and to reveal dynamic exciton modulation, and carrier localization and activation dynamics in the technologically important megahertz to gigahertz frequency range.

Does the gender of emergency physicians have an impact on the prehospital care of psychiatric emergencies? a retrospective cohort analysis.

BACKGROUND: Psychiatric emergencies pose a special challenge for emergency physicians. It is known from other areas of medicine that the influence of a doctor's gender can have an impact on the type of treatment and quality of patient care. However, this has not yet been investigated in the context of prehospital care in psychiatric emergencies. OBJECTIVES: To identify whether the gender of the prehospital emergency physicians has an influence on the "on-scene" time, treatment strategy and on the potential escalation of interventions for patients with a psychiatric diagnosis. METHODS: A retrospective cohort analysis of emergency missions with a psychiatric diagnosis was performed between January 1, 2015 and December 31, 2021 at the Department of Emergency Medicine, Department of Anesthesiology and Intensive Care Medicine, University Hospital Ulm, Germany. RESULTS: 2882 emergency missions with a psychiatric indication/prehospital psychiatric diagnosis were studied and divided into: intoxication (n = 1343, 46.6%), suicidal behavior (n = 488, 16.9%), exceptional mental situation (n = 282, 9.8%), agitation (n = 262, 9.1%), anxiety and panic disorders (n = 262, 9.1%) and "psychiatric miscellaneous" (n = 245, 8.5%). Inpatient hospitalization occurred in 67.9% (n = 1958) of emergency missions. Of these, 20.3% (n = 392) were admitted directly to a psychiatric hospital. Male emergency physicians had a slightly longer "on-scene" time for psychiatric emergencies than female emergency physicians (p = 0.024). However, the variance in "on-scene" time for all interventions was significantly greater for female emergency physicians than for male emergency physicians (p = 0.025). Male emergency physicians were significantly more likely than their female counterparts to administer intravenous hypnotics in prehospital psychiatric emergencies (p = 0.001). For psychiatric patients who refused medically indicated inpatient psychiatric admission ("involuntary psychiatric admission"), male and female emergency physicians were equally likely to take the required action (p = 0.522). However, male emergency physicians were significantly more likely to administer an intravenous hypnotic to enforce involuntary admission (p = 0.009). CONCLUSIONS: Similar to other medical specialties where the influence of physician gender on patient care is certainly relevant, the gender of prehospital emergency physicians also appears to influence their prehospital management strategy in psychiatric emergencies. The influence of gender is sometimes subtle and limited to specific aspects, such as the administration of hypnotics. Prospective study designs are needed to thoroughly investigate the influence of the gender of the prehospital emergency physician on the quality of care in psychiatric emergencies. TRIAL REGISTRATION: The study was approved by the ethics committee of the University Ulm, Trial-Code No. 110/22 and was prospectively registered in the German Clinical Trials Register (DRKS-ID: DRKS00031237). Patient information was not required for retrospective data analysis.

[Nasal hemorrhage - risk factors and management in 707 outpatient and inpatient patients]. / Epistaxis ­ Risikofaktoren und Management bei 707 ambulant und stationär geführten Patienten.

Epistaxis is one of the most common emergencies in otorhinolaryngology. The spectrum ranges from mild, self-limiting cases to life-threatening hemorrhages. Depending on the severity and course of the condition, management can be either outpatient or involve inpatient monitoring, possibly with surgical treatment.A retrospective systematic evaluation was conducted on all outpatient and inpatient patient data diagnosed with epistaxis from January to December 2021. Epistaxis associated with tumors, trauma, and postoperative epistaxis were excluded.A total of 707 patients were included. Seasonally, the highest number of patients presented in January. Outpatient management was possible for 80.8% of the cases, while 19.2% required inpatient admission. Among the inpatients, 15.4% required surgical intervention. Within the entire study cohort, 61.1% of the patients were male. Among the inpatients who underwent surgical treatment, the proportion of male patients was even higher (81.0%). The majority (73.1%) of the inpatients were on at least one anticoagulant medication. Advanced age (p=0.044) and the presence of posterior epistaxis (p<0.001) were significantly associated with the need for inpatient treatment. No children required inpatient care.Epistaxis is a common condition in otorhinolaryngology, predominantly affecting older male patients and those on anticoagulant therapy in severe cases within the studied cohort. Surgical intervention under general anesthesia was infrequently necessary for the treatment of epistaxis in the overall study population (3%).

Early CA2 Tau Inclusions Do Not Distinguish an Age-Related Tauopathy from Early Alzheimer's Disease.

Background: Neuropathologic studies of brains from autopsy series show tau inclusions (pretangles, neuropils threads, neurofibrillary tangles) are detectable more than a decade before amyloid-ß (Aß) deposition in Alzheimer's disease (AD) and develop in a characteristic manner that forms the basis for AD staging. An alternative position views pathological tau without Aß deposition as a 'primary age-related tauopathy' (PART) rather than prodromal AD. Recently, an early focus of tau inclusions in the Ammon's horn second sector (CA2) with relative sparing of CA1 that occurs before tau inclusions develop in the entorhinal cortex (EC) was proposed as an additional feature of PART. Objective: To test the 'definite PART' hypothesis. Methods: We used AT8-immunohistochemistry in 100µm sections to examine the EC, transentorhinal cortex (TRE), and Ammon's horn in 325 brains with tau inclusions lacking Aß deposits (average age at death 66.7 years for females, 66.4 years for males). Results: 100% of cases displayed tau inclusions in the TRE. In 89% of cases, the CA1 tau rating was greater than or equal to that in CA2. In 25%, CA2 was devoid of tau inclusions. Only 4% displayed a higher tau score in CA2 than in the TRE, EC, and CA1. The perforant path also displayed early tau changes. APOE genotyping was available for 199/325 individuals. Of these, 44% had an ɛ4 allele that placed them at greater risk for developing later NFT stages and, therefore, clinical AD. Conclusions: Our new findings call into question the PART hypothesis and are consistent with the idea that our cases represent prodromal AD.

Undetectable PSA predicts outcome after salvage radiotherapy for biochemical recurrence following radical prostatectomy.

BACKGROUND AND PURPOSE: Salvage radiotherapy (SRT) is a curative treatment option in patients with biochemical recurrence after radical prostatectomy (RP). Undetectable prostate-specific antigen (PSA) < 0.1 ng/mL following SRT predicts biochemical progression-free survival (BPFS). The aim of this large retrospective study was to evaluate whether this effect persists in an extended follow-up of >5 years. MATERIALS AND METHODS: A total of 678 patients treated with SRT for biochemical recurrence after RP were included. Exclusion criteria were lymph node or distant metastases, pre-SRT PSA > 3 ng/mL, and receipt of androgen deprivation therapy (ADT) between RP and SRT. All patients received a median dose of 70.2 (range 59.4-72.0) Gy to the prostatic fossa. The log-rank test (Kaplan-Meier) and Cox regression analysis were used to evaluate the impact of disease- and treatment-related parameters on BPFS, metastasis-free survival (MFS), and overall survival (OS). RESULTS: Median follow-up after SRT was 5.6 (range 0.1-14.5) years. The 5-year BPFS was 77.8 % in patients with a PSA nadir < 0.1 ng/mL (undetectable) and 16.3 % in the remaining cohort (p < 0.001). Five-year MFS was 95.3 % with undetectable PSA versus 84.0 % with detectable PSA (p < 0.001), and 5-year OS values were 97.5 % and 92.7 % with undetectable versus detectable PSA, respectively (p = 0.04). In multivariate analysis, undetectable PSA was the strongest predictor of BPFS (HR = 0.122; 95 %CI: 0.080-0.187; p < 0.001) and MFS (HR = 0.262; 95 %CI: 0.136-0.594; p < 0.001), but was not significant for OS (HR = 0.615; 95 %CI: 0.298-1.269; p = 0.189). CONCLUSION: PSA < 0.1 ng/mL following SRT without ADT is a significant predictor of BPFS and MFS. The results suggest that it might be feasible to withhold ADT in selected patients if they have undetectable PSA after SRT. Prospective studies are warranted to confirm these findings.

Population-Based Evidence for the Use of Serum Neurofilaments as Individual Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis.

OBJECTIVE: Neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains (pNfH), established as diagnostic and prognostic biomarkers in hospital-based amyotrophic lateral sclerosis (ALS) cohorts, are now surrogate markers in clinical trials. This study extends their evaluation to a population level, with the aim of advancing their full establishment and assessing the transferability of biomarker findings from controlled cohorts to real-world ALS populations. METHODS: We measured serum NfL and pNfH levels in all ALS patients (n = 790) and general population controls (n = 570) with available baseline samples participating in the epidemiological ALS Registry Swabia, providing platform-specific (ELLA™) reference data and Z-scores for controls, as well as reference data, disease-specific Z-scores and longitudinal data in ALS. We evaluated the diagnostic and prognostic utility of neurofilaments and quantified the impact of ALS-related factors and non-ALS confounders. RESULTS: Neurofilaments showed high diagnostic and prognostic utility at the population level, with NfL superior to pNfH. The novel concept of a population-based ALS Z-score significantly improved the prognostic utility compared to absolute raw values. Both biomarkers increased more strongly with age in controls than in ALS, and age adjustment improved diagnostic accuracy. Our data show that disease progression rates, ALS phenotype, body mass index (BMI), and renal function need to be considered when interpreting neurofilament levels; longitudinal neurofilament levels were generally stable in individual patients, especially when adjusted for age and baseline levels. INTERPRETATION: Population-based assessment enhances the utility of particularly serum NfL as a diagnostic and prognostic biomarker in ALS and improves the translation of findings from controlled cohorts to real-world populations. ANN NEUROL 2024.

Outcome after decompressive craniectomy in older adults after traumatic brain injury.

Objective: Globally, many societies are experiencing an increase in the number of older adults (>65 years). However, there has been a widening gap between the chronological and biological age of older adults which trend to a more active and social participating part of the society. Concurrently, the incidence of traumatic brain injury (TBI) is increasing globally. The aim of this study was to investigate the outcome after TBI and decompressive craniectomy (DC) in older adults compared with younger patients. Methods: A retrospective, multi-centre, descriptive, observational study was conducted, including severe TBI patients who were treated with DC between 2005 and 2022. Outcome after discharge and 12 months was evaluated according to the Glasgow Outcome Scale (Sliding dichotomy based on three prognostic bands). Significance was established as p ≤ 0.05. Results: A total of 223 patients were included. The majority (N = 158, 70.9%) survived TBI and DC at discharge. However, unfavourable outcome was predominant at discharge (88%) and after 12 months (67%). There was a difference in favour of younger patients (≤65 years) between the age groups at discharge (p = 0.006) and at 12 months (p < 0.001). A subgroup analysis of the older patients (66 to ≤74 vs. ≥75 years) did not reveal any significant differences. After 12 months, 64% of the older patients had a fatal outcome. Only 10% of those >65 years old had a good or very good outcome. 25% were depending on support in everyday activities. After 12 months, the age (OR 0.937, p = 0.007, CI 95%: 0.894-0.981; univariate) and performed cranioplasty (univariate and multivariate results) were influential factors for the dichotomized GOS. For unfavourable outcome after 12 months, the thresholds were calculated for age = 55.5 years (p < 0.001), time between trauma and surgery = 8.25 h (p = 0.671) and Glasgow Coma Scale (GCS) = 4 (p = 0.429). Conclusion: Even under the current modern conditions of neuro-critical care, with significant advances in intensive care and rehabilitation medicine, the majority of patients >65 years of age following severe TBI and DC died or were dependent and usually required extensive support. This aspect should also be taken into account during decision making and counselling (inter-, intradisciplinary or with relatives) for a very mobile and active older section of society, together with the patient's will.

Loss-of-function/gain-of-function polymorphisms of the ATP sensitive P2X7R influence sepsis, septic shock, pneumonia, and survival outcomes.

Introduction: Extracellular ATP (eATP) released from damaged cells activates the P2X7 receptor (P2X7R) ion channel on the surface of surrounding cells, resulting in calcium influx, potassium efflux and inflammasome activation. Inherited changes in the P2X7R gene (P2RX7) influence eATP induced responses. Single nucleotide polymorphisms (SNPs) of P2RX7 influence both function and signaling of the receptor, that in addition to ion flux includes pathogen control and immunity. Methods: Subjects (n = 105) were admitted to the ICU at the University Hospital Ulm, Germany between June 2018 and August 2019. Of these, subjects with a diagnosis of sepsis (n = 75), were also diagnosed with septic shock (n = 24), and/or pneumonia (n = 42). Subjects with pneumonia (n = 43) included those without sepsis (n = 1), sepsis without shock (n = 29) and pneumonia with septic shock (n = 13). Out of the 75 sepsis/septic shock patients, 33 patients were not diagnosed with pneumonia. Controls (n = 30) were recruited to the study from trauma patients and surgical patients without sepsis, septic shock, or pneumonia. SNP frequencies were determined for 16 P2RX7 SNPs known to affect P2X7R function, and association studies were performed between frequencies of these SNPs in sepsis, septic shock, and pneumonia compared to controls. Results: The loss-of-function (LOF) SNP rs17525809 (T253C) was found more frequently in patients with septic shock, and non-septic trauma patients when compared to sepsis. The LOF SNP rs2230911 (C1096G) was found to be more frequent in patients with sepsis and septic shock than in non-septic trauma patients. The frequencies of these SNPs were even higher in sepsis and septic patients with pneumonia. The current study also confirmed a previous study by our group that showed a five SNP combination that included the GOF SNPs rs208294 (C489T) and rs2230912 (Q460R) that was designated #21211 was associated with increased odds of survival in severe sepsis. Discussion: The results found an association between expression of LOF P2RX7 SNPs and presentation to the ICU with sepsis, and septic shock compared to control ICU patients. Furthermore, frequencies of LOF SNPs were found to be higher in sepsis patients with pneumonia compared to those without pneumonia. In addition, a five SNP GOF combination was associated with increased odds of survival in severe sepsis. These results suggest that P2RX7 is required to control infection in pneumonia and that inheritance of LOF variants increases the risk of sepsis when associated with pneumonia. This study confirms that P2RX7 genotyping in pneumonia may identify patients at risk of developing sepsis. The study also identifies P2X7R as a target in sepsis associated with an excessive immune response in subjects with GOF SNP combinations.

Interactional competencies in medical student admission- what makes a "good medical doctor"?

Doctors' interactional competencies play a crucial role in patient satisfaction, well-being, and compliance. Accordingly, it is in medical schools' interest to select candidates with strong interactional abilities. While Multiple Mini Interviews (MMIs) provide a useful context to assess such abilities, the evaluation of candidate performance during MMIs is not always based on a solid theoretical framework. The newly developed selection procedure "Interactional Competencies - Medical Doctors (IC-MD)" uses an MMI circuit with five simulation patient scenarios and is rated based on the theoretically and empirically grounded construct of emotional availability. A first validation study with N = 70 first-semester medical students took place in 2021. In terms of convergent validity, IC-MD ratings showed strong correlations with simulation patients' satisfaction with the encounter (r =.57) but no association with emotional intelligence measures. IC-MD ratings were not related to high school performance or a cognitive student aptitude test, indicating divergent validity. Inter-rater reliability (ICC = 0.63) and generalizability (Eρ2 = 0.64) were satisfactory. The IC-MD proved to be fair regarding participants' age and gender. Participants with prior work experience in healthcare outperformed those without such experience. Participant acceptance of the procedure were good. The IC-MD is a promising selection procedure capable of assessing interactional competencies relevant to the medical setting. Measures of interactional competencies can complement the use of cognitive selection criteria in medical student admission. The predictive validity of the IC-MD needs to be addressed in future studies.

Feasibility of aligning creatine kinase MB activity and mass data in multicentre trials using generalized additive modelling.

OBJECTIVES: Elevated serum creatine kinase isoenzyme MB (CK-MB) levels indicate myocardial ischaemia and periprocedural myocardial injury during treatment of heart diseases. We established a method to predict CK-MB mass from activity data based on a prospective pilot study in order to simplify multicentre trials. METHODS: 38 elective cardiac surgery patients without acute myocardial ischaemia and terminal renal failure were recruited. CK-MB mass and activity were determined in venous blood samples drawn preoperatively, postoperatively, 6 h post-op, and 12 h post-op. Linear regression and generalized additive models (GAMs) were applied to describe the relationship of mass and activity. Influences of demographic and perioperative factors on the fit of GAMs was evaluated. The agreement of predicted and measured CK-MB masses was assessed by Bland-Altman analyses. RESULTS: Linear regression provided an acceptable overall fit (r2 = 0.834) but showed deviances at low CK-MB levels. GAMs did not benefit from the inclusion of age, body mass index and surgical times. The minimal adequate model predicted CK-MB masses from activities, sex and sampling time with an r2 of 0.981. Bland-Altman analyses confirmed narrow limits of agreement (spread: 8.87 µg/l) and the absence of fixed (P = 0.41) and proportional (P = 0.21) biases. CONCLUSIONS: GAM-based modelling of CK-MB data in a representative patient cohort allowed to predict CK-MB masses from activities, sex and sampling time. This approach simplifies the integration of study centres with incompatible CK-MB data into multicentre trials in order to facilitate inclusion of CK-MB levels in statistical models.

Dynamics of synaptic damage in severe traumatic brain injury revealed by cerebrospinal fluid SNAP-25 and VILIP-1.

BACKGROUND: Biomarkers of neuronal, glial cells and inflammation in traumatic brain injury (TBI) are available but they do not specifically reflect the damage to synapses, which represent the bulk volume of the brain. Experimental models have demonstrated extensive involvement of synapses in acute TBI, but biomarkers of synaptic damage in human patients have not been explored. METHODS: Single-molecule array assays were used to measure synaptosomal-associated protein-25 (SNAP-25) and visinin-like protein 1 (VILIP-1) (along with neurofilament light chain (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillar acidic protein (GFAP), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in ventricular cerebrospinal fluid (CSF) samples longitudinally acquired during the intensive care unit (ICU) stay of 42 patients with severe TBI or 22 uninjured controls. RESULTS: CSF levels of SNAP-25 and VILIP-1 are strongly elevated early after severe TBI and decline in the first few days. SNAP-25 and VILIP-1 correlate with inflammatory markers at two distinct timepoints (around D1 and then again at D5) in follow-up. SNAP-25 and VILIP-1 on the day-of-injury have better sensitivity and specificity for unfavourable outcome at 6 months than NFL, UCH-L1 or GFAP. Later elevation of SNAP-25 was associated with poorer outcome. CONCLUSION: Synaptic damage markers are acutely elevated in severe TBI and predict long-term outcomes, as well as, or better than, markers of neuroaxonal injury. Synaptic damage correlates with initial injury and with a later phase of secondary inflammatory injury.

Health-related quality of life in patients with peripheral nerve tumors: results from the German multicentric Peripheral Nerve Tumor Registry.

Objective: Peripheral nerve tumors (PNTs) are rare diseases. So far, no multicenter data on diagnostics, the efficacy of treatment, long-term outcomes, and health-related quality of life (HRQoL) exist. The establishment of the Peripheral Nerve Tumor Registry (PNTR) in 2015 allows for the systematic analysis of patients with tumors associated with peripheral nerves. The present study aims to investigate the impact of PNT on an individual's HRQoL and the effect of surgery. Methods: HRQoL was pre- and postoperatively assessed by the Euro-Qol-5D-5L (EQ-5D-5L) and Euro-Qol visual analog scale (EQ-VAS) survey in the retrospective and prospective study arm in three active participating study centers. An index was calculated based on the EQ-5D-5L for the quantification of health state (0: worst possible state of health, 1: best possible state of health). The EQ-VAS ranges from 0% (worst imaginable health status) to 100% (best possible health status). Patient characteristics (age, sex), as well as disease (histopathological entity) and treatment (pre- and postoperative symptoms, type of treatment)-specific data, were analyzed. Results: Data from 171 patients from three high-volume centers were included, with schwannoma (70.8%, n = 121) and neurofibroma (15.8%, n = 27) being the most prevalent histopathological diagnoses. Both the median health index value (preoperative: 0.887, n = 167; postoperative: 0.910, n = 166) and the median EQ-VAS (preoperative: 75%, n = 167; postoperative: 85%, n = 166) of the entire cohort regarding all histopathological diagnosis improved significantly after surgical therapy (p < 0.001). Preoperatively, 12.3% (n = 21) reached the highest index score of 1.0 in EQ-5D-5L and 100% in the EQ-VAS score in 5.3% (n = 9) of all patients. Postoperatively, the highest index score of 1.0 and 100% in the EQ-VAS score increased significantly and were achieved in 33.3% (n = 57) and 11.1% (n = 19) of the patients, respectively (p < 0.001). Conclusion: For the first time, our study presents multicenter data on life quality and the effect of surgery in primarily benign peripheral nerve tumors. Early surgery at a specialized center could improve neurological outcomes and, in conclusion, better QoL. In summary, surgical therapy significantly improved the entire cohort's QoL, VAS, and analgesia.

Outcome after Intracerebral Haemorrhage and Decompressive Craniectomy in Older Adults.

OBJECTIVE: There is a relationship between the incidence of spontaneous intracerebral haemorrhage (ICH) and age. The incidence increases with age. This study aims to facilitate the decision-making process in the treatment of ICH. It therefore investigated the outcome after ICH and decompressive craniectomy (DC) in older adults (>65 years of age). METHODS: Retrospective, multicentre, descriptive observational study including only consecutive patients who received DC as the consequence of ICH. Additive evacuation of ICH was performed after the individual decision of the neurosurgeon. Besides demographic data, clinical outcomes both at discharge and 12 months after surgery were evaluated according to the Glasgow Outcome Scale (GOS). Patients were divided into age groups of ≤65 and >65 years and cohorts with favourable outcome (GOS IV-V) and unfavourable outcome (GOS I to III). RESULTS: 56 patients were treated. Mean age was 53.3 (SD: 16.13) years. There were 41 (73.2%) patients aged ≤65 years and 15 (26.8%) patients aged >65 years. During hospital stay, 10 (24.4%) patients in the group of younger (≤65 years) and 5 (33.3%) in the group of older patients (>65 years) died. Mean time between ictus and surgery was 44.4 (SD: 70.79) hours for younger and 27.9 (SD: 41.71) hours for older patients. A disturbance of the pupillary function on admission occurred in 21 (51.2%) younger and 2 (13.3%) older patients (p = 0.014). Mean arterial pressure was 99.9 (SD: 17.00) mmHg for younger and 112.9 (21.80) mmHg in older patients. After 12 months, there was no significant difference in outcome between younger patients (≤65 years) and older patients (>65 years) after ICH and DC (p = 0.243). Nevertheless, in the group of younger patients (≤65 years), 9% had a very good and 15% had a good outcome. There was no good recovery in the group of older patients (>65 years). CONCLUSION: Patients >65 years of age treated with microsurgical haematoma evacuation and DC after ICH are likely to have a poor outcome. Furthermore, in the long term, only a few older adults have a good functional outcome with independence in daily life activities.

COMBAT-C: COntrol of Major Bleeding by Application of Tourniquets over Clothing.

INTRODUCTION: External bleeding is the leading cause of preventable trauma-related death. In certain circumstances, tourniquet application over clothing may be necessary. Therefore, the aim of this study was to assess the effectiveness of tourniquets over different clothing setups. METHODS: Three windlass tourniquets (CAT, SAMXT, SOFTT-W) were applied over nine different clothing setups and without clothing on the Hapmed™ Tourniquet Trainer. We compared each tourniquet in each clothing setup to the tourniquet trainer that was not dressed, and we compared the three tourniquets within each clothing setup concerning blood loss, applied pressure and application time. Regression analysis of the effect of thickness, mean weight, mean deformation, application time, and applied pressure on blood loss was performed. RESULTS: Although blood loss was significantly greater in the CAT and SAMXT tourniquets when they were applied over leather motorcycle trousers, the overall findings showed that the clothing setups significantly reduced or did not affect blood loss. The mean blood loss was the lowest with CAT and the highest with SOFTT-W. The measured mean pressures were lower than 180 mmHg in four out of nine clothing setups with SOFTT-W, but CAT and SAMXT always exceeded this threshold. CAT had the fastest application time. Blood loss was significantly influenced by applied pressure and application time but was influenced to a far lesser degree by clothing parameters. CONCLUSION: The effects of the clothing setups were of little clinical relevance, except for leather motorcycle trousers. The effects of rugged protective equipment, e.g., hazard suits, are conceivable and need to be tested for specific garments with the tourniquet intended for use. No clothing parameter for predicting tourniquet effectiveness could be identified.

Serum neurofilament light chain and glial fibrillary acidic protein for predicting response to apheresis in steroid-refractory multiple sclerosis relapses.

BACKGROUND AND PURPOSE: The predictive value of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) for apheresis outcome in steroid-refractory multiple sclerosis (MS) relapse has not yet been evaluated. METHODS: We used pre- and postapheresis serum samples from 38 participants of the IAPEMS trial (clinicaltrials.gov: NCT02671682), which investigated the use of immunoadsorption versus plasma exchange for the treatment of steroid-refractory MS attacks. Response to apheresis was classified based on improvement on (i) the Expanded Disability Status Scale (EDSS), (ii) the affected functional system scores (FSS) of the EDSS, or (iii) the visual acuity for patients with optic neuritis, 4 weeks postapheresis. sNFL and sGFAP were measured by single molecule arrays. RESULTS: Preprocedural sGFAP levels could discriminate between responders and nonresponders, determined by FSS improvement (p = 0.017). In multivariate logistic regression analysis, younger age (odds ratio [OR] = 0.781, 95% confidence interval [CI] = 0.635-0.962, p = 0.020) and lower sGFAP levels (OR = 0.948, 95% CI = 0.903-0.995, p = 0.031) could predict response to apheresis in the overall cohort. We could observe a trend towards a favourable apheresis outcome with higher sNfL levels (OR = 1.413, 95% CI = 0.965-2.069, p = 0.076). Analysis of the sNfL-to-sGFAP ratio showed an OR of 1.924 (95% CI = 1.073-3.451, p = 0.028) for predicting apheresis response. The ratio showed a better predictive value than the individual parameters. Neither biomarker was affected by the number of steroid cycles preapheresis. CONCLUSIONS: Lower sGFAP levels, a higher sNfL-to-sGFAP ratio, and younger age are associated with a favourable apheresis outcome.

Long-Term Oncologic Outcome following Duodenum-Preserving Pancreatic Head Resection for Benign Tumors, Cystic Neoplasms, and Neuroendocrine Tumors: Systematic Review and Meta-analysis.

BACKGROUND: Pancreatoduodenectomy (PD) has a considerable surgical risk for complications and late metabolic morbidity. Parenchyma-sparing resection of benign tumors has the potential to cure patients associated with reduced procedure-related short- and long-term complications. MATERIALS AND METHODS: Pubmed, Embase, and Cochrane libraries were searched for studies reporting surgery-related complications following PD and duodenum-preserving total (DPPHRt) or partial (DPPHRp) pancreatic head resection for benign tumors. A total of 38 cohort studies that included data from 1262 patients were analyzed. In total, 729 patients underwent DPPHR and 533 PD. RESULTS: Concordance between preoperative diagnosis of benign tumors and final histopathology was 90.57% for DPPHR. Cystic and neuroendocrine neoplasms (PNETs) and periampullary tumors (PATs) were observed in 497, 89, and 31 patients, respectively. In total, 34 of 161 (21.1%) patients with intraepithelial papillar mucinous neoplasm exhibited severe dysplasia in the final histopathology. The meta-analysis, when comparing DPPHRt and PD, revealed in-hospital mortality of 1/362 (0.26%) and 8/547 (1.46%) patients, respectively [OR 0.48 (95% CI 0.15-1.58); p = 0.21], and frequency of reoperation of 3.26 % and 6.75%, respectively [OR 0.52 (95% CI 0.28-0.96); p = 0.04]. After a follow-up of 45.8 ± 26.6 months, 14/340 patients with intraductal papillary mucinous neoplasms/mucinous cystic neoplasms (IPMN/MCN, 4.11%) and 2/89 patients with PNET (2.24%) exhibited tumor recurrence. Local recurrence at the resection margin and reoccurrence of tumor growth in the remnant pancreas was comparable after DPPHR or PD [OR 0.94 (95% CI 0.178-5.34); p = 0.96]. CONCLUSIONS: DPPHR for benign, premalignant neoplasms provides a cure for patients with low risk of tumor recurrence and significantly fewer early surgery-related complications compared with PD. DPPHR has the potential to replace PD for benign, premalignant cystic and neuroendocrine neoplasms.

European association of urology risk stratification predicts outcome in patients receiving PSMA-PET-planned salvage radiotherapy for biochemical recurrence following radical prostatectomy.

PURPOSE: The European Association of Urology (EAU) proposed a risk stratification (high vs. low risk) for patients with biochemical recurrence (BR) following radical prostatectomy (RP). Here we investigated whether this stratification accurately predicts outcome, particularly in patients staged with PSMA-PET. METHODS: For this study, we used a retrospective database including 1222 PSMA-PET-staged prostate cancer patients who were treated with salvage radiotherapy (SRT) for BR, at 11 centers in 5 countries. Patients with lymph node metastases (pN1 or cN1) or unclear EAU risk group were excluded. The remaining cohort comprised 526 patients, including 132 low-risk and 394 high-risk patients. RESULTS: The median follow-up time after SRT was 31.0 months. The 3-year biochemical progression-free survival (BPFS) was 85.7 % in EAU low-risk versus 69.4 % in high-risk patients (p = 0.002). The 3-year metastasis-free survival (MFS) was 94.4 % in low-risk versus 87.6 % in high-risk patients (p = 0.005). The 3-year overall survival (OS) was 99.0 % in low-risk versus 99.6 % in high-risk patients (p = 0.925). In multivariate analysis, EAU risk group remained a statistically significant predictor of BPFS (p = 0.003, HR 2.022, 95 % CI 1.262-3.239) and MFS (p = 0.013, HR 2.986, 95 % CI 1.262-7.058). CONCLUSION: Our data support the EAU risk group definition. EAU risk grouping for BCR reliably predicted outcome in patients staged lymph node-negative after RP and with PSMA-PET before SRT. To our knowledge, this is the first study validating the EAU risk grouping in patients treated with PSMA-PET-planned SRT.

Linking Gene Fusions to Bone Marrow Failure and Malignant Transformation in Dyskeratosis Congenita.

Dyskeratosis Congenita (DC) is a multisystem disorder intrinsically associated with telomere dysfunction, leading to bone marrow failure (BMF). Although the pathology of DC is largely driven by mutations in telomere-associated genes, the implications of gene fusions, which emerge due to telomere-induced genomic instability, remain unexplored. We meticulously analyzed gene fusions in RNA-Seq data from DC patients to provide deeper insights into DC's progression. The most significant DC-specific gene fusions were subsequently put through in silico assessments to ascertain biophysical and structural attributes, including charge patterning, inherent disorder, and propensity for self-association. Selected candidates were then analyzed using deep learning-powered structural predictions and molecular dynamics simulations to gauge their potential for forming higher-order oligomers. Our exploration revealed that genes participating in fusion events play crucial roles in upholding genomic stability, facilitating hematopoiesis, and suppressing tumors. Notably, our analysis spotlighted a particularly disordered polyampholyte fusion protein that exhibits robust higher-order oligomerization dynamics. To conclude, this research underscores the potential significance of several high-confidence gene fusions in the progression of BMF in DC, particularly through the dysregulation of genomic stability, hematopoiesis, and tumor suppression. Additionally, we propose that these fusion proteins might hold a detrimental role, specifically in inducing proteotoxicity-driven hematopoietic disruptions.