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.

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.

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.

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.

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.

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.

Hemostatics in patients with inhibited coagulation-A viscoelastic in-vitro analysis.

BACKGROUND: The military has used topical hemostatic agents to successfully treat life-threatening external bleeding for years. In contrast to the military environment, the general population are increasingly prescribed anticoagulants. There are only few comparative evaluations of topical hemostatic agents with anticoagulated human blood. It is important to understand the impact of these agents on those who take anticoagulants. STUDY DESIGN AND METHODS: Citrated blood of patients treated with enoxaparin, heparin, and acetylsalicylic acid, apixaban or phenprocoumon was incubated with different hemostatic agents (QuikClot Gauze, Celox Granules, Celox Gauze, Chito SAM 100, WoundClot Trauma Gauze, QuikClot Gauze Moulage Trainer and Kerlix) and rotational thromboelastometry was performed with non-activated thromboelastometry (NATEM reagent). RESULTS: All tested agents improved the onset of coagulation in all anticoagulants, mostly to a significant degree. Most significant improvements were produced by QuikClot Gauze and QuikClot Gauze Moulage Trainer, followed by the tested chitosans (Celox Granules, Celox Gauze, Chito SAM 100). Of the anticoagulant groups, the most significant improvements were seen in enoxaparin. This was followed in order by apixaban, heparin, and acetylsalicylic acid, and phenprocoumon. DISCUSSION: All the hemostatic agents tested were able to activate the clotting cascade earlier and initiate faster clot formation in anticoagulated blood. A definitive head-to-head comparison is not feasible, because of the limitations of an in-vitro analysis. However, the sometimes-presented hypothesis that kaolin-based hemostatic agents are ineffective in anticoagulated blood is inaccurate according to our data. Hemostasis with hemostatic agents appears most challenging with phenprocoumon.

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.

Value of Proximal Femur Geometry in Predicting Occult Hip Fracture.

Background and Objectives: Patients with occult hip fractures are a difficult subgroup to treat. MRI is the gold standard for diagnosing occult proximal femur fractures but is costly and may not be readily available in an emergency setting. The purpose of this study was to determine whether changes in the proximal femur geometry can predict the likelihood of an occult hip fracture in patients presenting with hip pain following a ground-level fall. Material and Methods: Patients admitted to the hospital with a clinical suspicion of a hip fracture but initial negative radiographs over a seven-year period were included. All patients were additionally investigated with an MRI scan, and retrospectively, six radiologic parameters were obtained on plain radiographs: The cortical thickness index (CTI), the canal to calcar ratio (CCR), the canal flare index (CFI), the morphological cortical index (MCI), the canal bone ratio (CBR) and the canal bone aria ratio (CBAR). Subsequently the result of the plain radiographic indices of the patients with a negative MRI (Group A, no occult fracture) were compared to those with a positive MRI (Group B, occult fracture). Results: A total of 78 patients (59 female, 19 male) could be included in the study. The mean age was 82 years. The univariate analyses revealed a poor predictive ability of all radiological parameters with AUC values ranging from 0.515 (CBR) to 0.626 (CTI), whereas a multivariate prognostic model demonstrated improved prognosis (AUC = 0.761) for the CTI (p = 0.024), CBAR (p = 0.074) and CRR (p = 0.081) as the most promising predictive radiological parameters. Conclusions: Single radiologic indices obtained from conventional X-rays of the proximal femur have a weak predictive value in detecting occult fractures of the hip and cannot be used as clinical decision-making factors.

Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation.

The peptidyl-prolyl-cis/trans-isomerase (PPIase) macrophage infectivity potentiator (Mip) contributes to the pathogenicity and fitness of L. pneumophila, the causative agent of Legionnaires' disease. Here, we identified the stringent starvation protein SspB, hypothetical protein Lpc2061, and flagellin FlaA as bacterial interaction partners of Mip. The macrolide FK506, which inhibits the PPIase activity of Mip, interfered with the binding of Lpc2061. Moreover, we demonstrated that the N-terminal dimerization region and amino acid Y185 in the C-terminal PPIase domain of Mip are required for the binding of Lpc2061 and FlaA. The modeling of the interaction partners and global docking with Mip suggested nonoverlapping binding interfaces, and a molecular dynamic simulation predicted an increased stability for the tripartite interaction of Lpc2061, Mip, and FlaA. On the functional level, we demonstrated that Mip promotes L. pneumophila flagellation, which is positively influenced by the binding of Lpc2061 and reduced by FK506. Also, L. pneumophila mutants expressing the Y185A or the monomeric Mip variant, which bind less Lpc2061, were nonmotile, were less flagellated, and yielded less FlaA when quantified. To our knowledge, this is the first report in which a PPIase and its bacterial interaction partners were demonstrated to influence flagellation.

Dog Ownership and Risk for Alveolar Echinococcosis, Germany.

Human alveolar echinococcosis is caused by the parasite Echinococcus multilocularis, and dog ownership has been identified as a risk factor. We sought to specify the factors of dog ownership underlying this risk by conducting a case-control study among dog owners in Germany. The analysis revealed an increased odds ratio of ≈7-fold for dog owners whose dogs roam unattended in fields, 13-fold for dog owners who feed their dogs organic waste daily, 4-fold for dog owners who take their dog to a veterinarian only in case of illness, and 10-fold for dog owners who have never been informed by a veterinarian about the risk for infection. The results highlight the risk for infection associated with various factors of dog ownership and the value of veterinarians informing owners about prevention.

Long-term Metabolic Morbidity and Steatohepatosis Following Standard Pancreatic Resections and Parenchyma-sparing, Local Extirpations for Benign Tumor: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess metabolic dysfunctions and steatohepatosis after standard and local pancreatic resections for benign and premalignant neoplasms. SUMMARY OF BACKGROUND DATA: Duodenopancreatectomy, hemipancreatectomy, and parenchyma-sparing, limited pancreatic resections are currently in use for nonmalignant tumors. METHODS: Medline, Embase, and Cochrane libraries were searched for studies reporting measured data of metabolic functions following PD, pancreatic left resection (PLR), duodenum-sparing pancreatic head resection (DPPHR), pancreatic middle segment resection (PMSR), and tumor enucleation (TEN). Forty cohort studies comprising data of 2729 patients were eligible. RESULTS: PD for benign tumor was associated in 46 of 327 patients (14.1%) with postoperative new onset of diabetes mellitus (pNODM) and in 109 of 243 patients (44.9%) with postoperative new onset of pancreatic exocrine insufficiency measured after a mean follow-up of 32 months. The meta-analysis displayed pNODM following PD in 32 of 204 patients (15.7%) and in 10 of 200 patients (5%) after DPPHR [P < 0.01; OR: 0.33; (95%-CI: 0.15-0.22)]. PEI was found in 77 of 174 patients following PD (44.3%) and in 7 of 104 patients (6.7%) following DPPHR (P < 0.01;OR: 0.15; 95%-CI: 0.07-0.32). pNODM following PLR was reported in 107 of 459 patients (23.3%) and following PMSR 23 of 412 patients (5.6%) (P < 0.01; OR: 0.20; 95%-CI: 0.12-0.32). Postoperative new onset of pancreatic exocrine insufficiency was found in 17% following PLR and in 8% following PMSR (P < 0.01). pNODM following PPPD and tumor enucleation was observed in 19.7% and 5.7% (P < 0.03) of patients, respectively. Following PD/PPPD, 145 of 608 patients (23.8%) developed a nonalcoholic fatty liver disease after a mean follow-up of 30.4 months. Steatohepatosis following DPPHR developed in 2 of 66 (3%) significantly lower than following PPPD (P < 0.01). CONCLUSION: Standard pancreatic resections for benign tumor carry a considerable high risk for a new onset of diabetes, pancreatic exocrine insufficiency and following PD for steatohepatosis. Parenchyma-sparing, local resections are associated with low grade metabolic dysfunctions.

Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS.

OBJECTIVE: Elevated levels of neurofilament light (NfL) and heavy (NfH) chain in amyotrophic lateral sclerosis (ALS) cerebrospinal fluid (CSF) and serum reflect neuro-axonal degeneration and are used as diagnostic biomarkers. However, studies comparing the differential diagnostic potential for ALS of all four parameters are missing. Here, we measured serum NfL/NfH and CSF NfL/NfH in a large cohort of ALS and other neurological disorders and analysed the differential diagnostic potential. METHODS: In total CSF and serum of 294 patients were analysed. The diagnostic groups comprised: ALS (n=75), frontotemporal lobar degeneration (FTLD) (n=33), Alzheimer's disease (n=20), Parkinson's disease (dementia) (n=18), Creutzfeldt-Jakob disease (n=11), non-neurodegenerative controls (n=77) (Con) and 60 patients who were seen under the direct differential diagnosis of a patient with ALS (Con.DD). RESULTS: CSF and serum NfL and NfH showed significantly increased levels in ALS (p<0.0001) compared with Con and Con.DD. The difference between ALS and FTLD was markedly stronger for NfH than for NfL. CSF and serum NfL demonstrated a stronger correlation (r=0.84 (95% CI 0.80 to 0.87), p<0.001) than CSF and serum NfH (r=0.68 (95% CI 0.61 to 0.75), p<0.0001). Comparing ALS and Con.DD, receiver operating characteristic analysis revealed the best area under the curve (AUC) value for CSF NfL (AUC=0.94, 95% CI 0.91 to 0.98), followed by CSF NfH (0.93, 95% CI 0.88 to 0.98), serum NfL (0.93, 95% CI 0.89 to 0.97) and serum NfH (0.88, 95% CI 0.82 to 0.94). CONCLUSION: Our results demonstrate that CSF NfL and NfH as well as serum NfL are equally suited for the differential diagnosis of ALS, whereas serum NfH appears to be slightly less potent.

Disease heterogeneity of adult diabetes based on routine clinical variables at diagnosis: Results from the German/Austrian Diabetes Follow-up Registry.

AIM: To cluster adults with diabetes using variables from real-world clinical care at manifestation. MATERIALS AND METHODS: We applied hierarchical clustering using Ward's method to 56 869 adults documented in the prospective Diabetes Follow-up Registry (DPV). Clustering variables included age, sex, body mass index (BMI), HbA1c, diabetic ketoacidosis (DKA), components of the metabolic syndrome (hypertension/dyslipidaemia/hyperuricaemia) and beta-cell antibody status. Time until use of oral antidiabetic drugs (OADs), use of insulin, chronic kidney disease (CKD), cardiovascular disease (CVD), retinopathy or neuropathy were assessed using Kaplan-Meier analysis and Cox regression models. RESULTS: We identified eight clusters: four clusters comprised early diabetes onset (median age 40-50 years) but differed with regard to BMI, HbA1c, DKA and antibody positivity. Two clusters included adults with diabetes onset aged in their early 60s who met target HbA1c, but differed in BMI and sex distribution. Two clusters were characterized by late diabetes onset (median age 69 and 77 years) and comparatively low BMI, but differences in HbA1c. Earlier insulin use was observed in adults with high HbA1c, and earlier OAD use was observed in those with high BMI. Time until CKD or CVD was shorter in those with late onset, whereas retinopathy occurred earlier in adults with late onset and high HbA1c, and in adults with early onset, but high HbA1c and high percentage of antibody positivity. CONCLUSIONS: Adult diabetes is heterogeneous beyond classical type 1/type 2 diabetes, based on easily available variables in clinical practice using an automated clustering algorithm that allows both continuous and binary variables.

Interventions for managing medication-related osteonecrosis of the jaw.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some individuals to certain medicines commonly used in the treatment of cancer and osteoporosis (e.g. bisphosphonates, denosumab, and antiangiogenic agents), and involves the progressive destruction of bone in the mandible or maxilla. Depending on the drug, its dosage, and the duration of exposure, this adverse drug reaction may occur rarely (e.g. following the oral administration of bisphosphonate or denosumab treatments for osteoporosis, or antiangiogenic agent-targeted cancer treatment), or commonly (e.g. following intravenous bisphosphonate for cancer treatment). MRONJ is associated with significant morbidity, adversely affects quality of life (QoL), and is challenging to treat. This is an update of our review first published in 2017. OBJECTIVES: To assess the effects of interventions versus no treatment, placebo, or an active control for the prophylaxis of MRONJ in people exposed to antiresorptive or antiangiogenic drugs. To assess the effects of non-surgical or surgical interventions (either singly or in combination) versus no treatment, placebo, or an active control for the treatment of people with manifest MRONJ. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched four bibliographic databases up to 16 June 2021 and used additional search methods to identify published, unpublished, and ongoing studies.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing one modality of intervention with another for the prevention or treatment of MRONJ. For 'prophylaxis of MRONJ', the primary outcome of interest was the incidence of MRONJ; secondary outcomes were QoL, time-to-event, and rate of complications and side effects of the intervention. For 'treatment of established MRONJ', the primary outcome of interest was healing of MRONJ; secondary outcomes were QoL, recurrence, and rate of complications and side effects of the intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results, extracted the data, and assessed the risk of bias in the included studies. For dichotomous outcomes, we reported the risk ratio (RR) (or rate ratio) and 95% confidence intervals (CIs). MAIN RESULTS: We included 13 RCTs (1668 participants) in this updated review, of which eight were new additions. The studies were clinically diverse and examined very different interventions, so meta-analyses could not be performed. We have low or very low certainty about available evidence on interventions for the prophylaxis or treatment of MRONJ. Prophylaxis of MRONJ Five RCTs examined different interventions to prevent the occurrence of MRONJ. One RCT compared standard care with regular dental examinations at three-month intervals and preventive treatments (including antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) in men with metastatic prostate cancer treated with zoledronic acid. The intervention seemed to lower the risk of MRONJ (RR 0.10, 95% CI 0.02 to 0.39, 253 participants). Secondary outcomes were not evaluated. Dentoalveolar surgery is considered a common predisposing event for developing MRONJ and five RCTs tested various preventive measures to reduce the risk of postoperative MRONJ. The studies evaluated plasma rich in growth factors inserted into the postextraction alveolus in addition to standardised medical and surgical care versus standardised medical and surgical care alone (RR 0.08, 95% CI 0.00 to 1.51, 176 participants); delicate surgery and closure by primary intention versus non-traumatic tooth avulsion and closure by secondary intention (no case of postoperative MRONJ in either group); primary closure of the extraction socket with a mucoperiosteal flap versus application of platelet-rich fibrin without primary wound closure (no case of postoperative MRONJ in either group); and subperiosteal wound closure versus epiperiosteal wound closure (RR 0.09, 95% CI 0.00 to 1.56, 132 participants).  Treatment of MRONJ Eight RCTs examined different interventions for the treatment of established MRONJ; that is, the effect on MRONJ cure rates.  One RCT analysed hyperbaric oxygen (HBO) treatment used in addition to standard care (antiseptic rinses, antibiotics, and surgery) compared with standard care alone (at last follow-up: RR 1.56, 95% CI 0.77 to 3.18, 46 participants).  Healing rates from MRONJ were not significantly different between autofluorescence-guided bone surgery and conventional bone surgery (RR 1.08, 95% CI 0.85 to 1.37, 30 participants). Another RCT that compared autofluorescence- with tetracycline fluorescence-guided sequestrectomy for the surgical treatment of MRONJ found no significant difference (at one-year follow-up: RR 1.05, 95% CI 0.86 to 1.30, 34 participants).  Three RCTs investigated the effect of growth factors and autologous platelet concentrates on healing rates of MRONJ: platelet-rich fibrin after bone surgery versus surgery alone (RR 1.05, 95% CI 0.90 to 1.22, 47 participants), bone morphogenetic protein-2 together with platelet-rich fibrin versus platelet-rich fibrin alone (RR 1.10, 95% CI 0.94 to 1.29, 55 participants), and concentrated growth factor and primary wound closure versus primary wound closure only (RR 1.38, 95% CI 0.81 to 2.34, 28 participants).   Two RCTs focused on pharmacological treatment with teriparatide: teriparatide 20 µg daily versus placebo in addition to standard care (RR 0.96, 95% CI 0.31 to 2.95, 33 participants) and teriparatide 56.5 µg weekly versus teriparatide 20 µg daily in addition to standard care (RR 1.60, 95% CI 0.25 to 1.44, 12 participants). AUTHORS CONCLUSIONS: Prophylaxis of medication-related osteonecrosis of the jaw One open-label RCT provided some evidence that dental examinations at three-month intervals and preventive treatments may be more effective than standard care for reducing the incidence of medication-related osteonecrosis of the jaw (MRONJ) in individuals taking intravenous bisphosphonates for advanced cancer. We assessed the certainty of the evidence to be very low. There is insufficient evidence to either claim or refute a benefit of the interventions tested for prophylaxis of MRONJ in patients with antiresorptive therapy undergoing dentoalveolar surgery. Although some interventions suggested a potential large effect, the studies were underpowered to show statistical significance, and replication of the results in larger studies is pending. Treatment of medication-related osteonecrosis of the jaw The available evidence is insufficient to either claim or refute a benefit, in addition to standard care, of any of the interventions studied for the treatment of MRONJ.

Central Serous Chorioretinopathy: Morphological and Functional Outcome after Subthreshold Thermal Laser Coagulation with a Frequency-Doubled Nd:YAG Continuous-Wave Laser.

PURPOSE: Central serous chorioretinopathy (CSCR) presents itself as a serous detachment of the central neurosensory retina (NR), which may be accompanied by focal detachment of the retinal pigment epithelium (RPE) and changes in the RPE itself. It is often self-limiting; however, if the macular region is affected, visual impairment can be serious. If spontaneous remission does not occur, data on the effectiveness of further treatment options are sparse. We therefore decided to examine the effectiveness of subthreshold laser photocoagulation (ST-LP) on best-corrected visual acuity (BCVA) and subretinal fluid (SRF) resorption. We conducted a retrospective analysis of all patients who underwent ST-LP based on the diagnosis of CSCR in a German university eye hospital from 2009 to 2014. METHODS: The diagnosis of CSCR was based on the following criteria: detachment of the NR and possibly the RPE visible on ophthalmoscopy, evidence of SRF on optical coherence tomography (OCT), visualization of one or more source points typical for CSCR in fluorescein angiography, and exclusion of differential diagnoses. The time between the anamnestic onset of symptomatic complaints and ST-LP was determined as well as BCVA and OCT before ST-LP. ST-LP was performed as a subthreshold thermal laser coagulation with a frequency-doubled Nd:YAG continuous-wave laser. Follow-up examinations were scheduled at 4, 8, and 12 weeks after ST-LP. RESULTS: Fifty-four eyes of 49 patients were included in the study. The median age of patients was 47 years. Eighty-nine percent of the included patients were male. Twenty percent of patients had a first manifestation of CSCR, 69% had a recurrence, and 11% had persistent SRF for >6 months. The median visual acuity rose from 0.30 at baseline (BL) to 0.10 at 4 weeks and 0.00 at 8 weeks, before dropping slightly to 0.05 at 12 weeks. Changes of visual acuity in comparison to BL were statistically significant (p < 0.05). The initial median retinal thickness of 397 µm at BL decreased to 264 µm at 4 weeks, to 236 µm at 8 weeks, and to 239 µm at 12 weeks (decreases to BL all statistically significant p < 0.05). CONCLUSION: In our cohort, we were able to achieve substantial and significant clinical benefit through ST-LP measured by improvement in BCVA. Furthermore, we were also able to demonstrate measurable, significant morphological improvements as decreased retinal thickness and increased resorption of SRF as probable mechanisms explaining clinical improvement of CSCR with ST-LP. The advantage of ST-LP over other methods is the low risk of adverse events and its high availability. Controlled, randomized studies are necessary to confirm the data and demonstrate the effect over a longer period of time.

Characterization of tumor remnants in intraoperative MRI-assisted microscopic and endoscopic transsphenoidal resection of less invasive pituitary adenomas.

INTRODUCTION: Intraoperative magnetic resonance imaging (iMRI) improves the intraoperative detection of adenoma remnants in transsphenoidal surgery. iMRI might be redundant in endoscopic pituitary surgery in non-invasive tumors (Knosp 0-2) due to a superior visualization of anatomical structures in the periphery of the sella turcica compared to the microscopic technique. We identified the anatomical location of tumor remnants in iMRI and evaluated risk factors for secondary resection after iMRI and hereby selected patients with pituitary adenomas who may benefit from iMRI-assisted resection. METHODS: We conducted a retrospective monocenter study of patients who underwent iMRI-assisted transsphenoidal surgical resection of pituitary adenomas at our department between 2012 and 2020. A total number of 190 consecutive iMRI-assisted transsphenoidal surgeries of pituitary adenomas graded as Knosp 0-2 were selected for analysis. Exclusion criteria were missing iMRI availability or pathologies other than adenomas. Of these 190 cases, 46.3% (N = 88) were treated with microscopic, 48.4% (N = 92) with endoscopic, and 5.3% (N = 10) with endoscopic-assisted technique. Volumetric measurement of preoperative, intraoperative, and postoperative tumor extension was performed. Demographic data, tumor characteristics, and MRI features were evaluated. Additionally, analysis of adenoma remnants identified by iMRI was performed. RESULTS: An additional resection after iMRI was performed in 16.3% (N = 31). iMRI helped to reach gross total resection (GTR) in 83.9% (26/31) of these cases. False-positive resection was found in 1 patient (0.5%). Multivariable logistic analysis identified tumor volume (OR = 1.2, p = 0.007) recurrence (OR = 11.3, p = 0.002) and microscopic technique (OR = 2.8, p = 0.029) as independent risk factors for additional resection. Simultaneously, the endoscopic technique was significantly associated with GTR as evaluated by iMRI (OR = 2.8, p = 0.011) and postoperative MRI (OR = 5.8, p = 0.027). The detailed analysis of adenoma remnants on iMRI revealed the suprasellar location in a diaphragm fold, penetrating tumor above the diaphragm, or undetected invasion of cavernous sinus as well as in case of microscopic resection tumor location outside the line of sight as the main reasons for incomplete resections. CONCLUSION: Tumor volume, recurrence, and microscopic technique were identified as independent predictors for additional resection in patients with Knosp 0-2 adenomas. iMRI might increase the extent of resection (EOR) safely even after the endoscopic visualization of the sella with very low risk for false-positive findings. Remnants of tumors hidden within the diaphragmic folds, intrathecally, or behind the infiltrated wall of cavernous sinus not recognized on preoperative MRI were the most common findings in iMRI.

Emergency medical care of patients with psychiatric disorders - challenges and opportunities: Results of a multicenter survey.

BACKGROUND: Pre-clinical psychiatric emergencies are generally treated by emergency medical staff. The subsequent clinical treatment is often conditioned by interaction problems between emergency medical staff and psychiatric clinical staff. OBJECTIVES: To identify problems affecting interaction between emergency medical and psychiatric care of mentally ill patients and pinpoint aspects of optimized emergency care. METHODS: To shed light on the interaction problems an anonymous, questionnaire-based, nonrepresentative survey of 98 emergency physicians (EM) and 104 psychiatrists (PS) practicing in acute psychiatry was conducted between March 1, 2021 and October 1, 2021. RESULTS: The chi-square test for multiple response sets revealed consistently significant differences (p < 0.001) between EM and PS with respect to the questions analyzed. Approximately 36% of EM reported not to be adequately qualified to handle psychiatric emergencies (p = 0.0001), while around 50% of respondents were neutral in their assessment in how to deal with psychiatric emergencies. 80% of EM reported a negative interaction (rejection of patients) with PS when referring a psychiatric emergency patient to the acute psychiatric unit. The most common reasons for refusal were intoxication (EM: 78.8%, PS: 88.2%), emergency physician therapy (EM: 53.8%, PS: 63.5%), and not resident in the catchment area of the hospital (EM 68.8%, PS: 48.2%). In the casuistry presented, most respondents would choose "talk down" for de-escalation (EM: 92.1%, PS: 91.3%). With respect to drug therapy, benzodiazepine is the drug of choice (EM: 70.4%, PS: 78.8%). More EM would choose an intravenously (i.v.) or a Mucosal Atomization Device (MAD) administration as an alternative to oral medication (i.v.: EM: 38.8%, PS: 3.8%, p = 0.001, MAD: EM: 36.7%, PS: 10.6%, p = 0.006). Significantly more EM would seek phone contact with the acute psychiatric hospital (EM: 84.7%, PS: 52.9%, p = 0.0107). A psychiatric emergency plan was considered useful in this context by more than 90% of respondents. The need for further training for EM with regard to treating psychiatric clinical syndromes was considered important by all respondents. In particular, the topics of "psychogenic seizure," "intoxication," and "legal aspects of psychiatric emergencies" were considered important (Mann-Whitney U test, p < 0.001). CONCLUSION: The interaction-related problems identified in the emergency medical care of pre-clinical psychiatric patients relate to non-modifiable, structural problems, such as insufficient admission capacity and non-existent or inadequate monitoring capabilities in acute psychiatric hospitals. However, factors such as the education and training of EM and communication between EM and PS can be improved. Developing personalized emergency care plans for psychiatric patients could help to optimize their care.

Utilization of Aminoguanidine Prevents Cytotoxic Effects of Semen.

Studies of human semen in cell or tissue culture are hampered by the high cytotoxic activity of this body fluid. The components responsible for the cell damaging activity of semen are amine oxidases, which convert abundant polyamines, such as spermine or spermidine in seminal plasma into toxic intermediates. Amine oxidases are naturally present at low concentrations in seminal plasma and at high concentrations in fetal calf serum, a commonly used cell culture supplement. Here, we show that, in the presence of fetal calf serum, seminal plasma, as well as the polyamines spermine and spermidine, are highly cytotoxic to immortalized cells, primary blood mononuclear cells, and vaginal tissue. Thus, experiments investigating the effect of polyamines and seminal plasma on cellular functions should be performed with great caution, considering the confounding cytotoxic effects. The addition of the amine oxidase inhibitor aminoguanidine to fetal calf serum and/or the utilization of serum-free medium greatly reduced this serum-induced cytotoxicity of polyamines and seminal plasma in cell lines, primary cells, and tissues and, thus, should be implemented in all future studies analyzing the role of polyamines and semen on cellular functions.

Smartphone Application to Reinforce Education Increases High-Quality Preparation for Colorectal Cancer Screening Colonoscopies in a Randomized Trial.

BACKGROUND & AIMS: Sufficient bowel preparation is crucial for successful screening and surveillance colonoscopy. However, rates of inadequate preparation are still high. We investigated the effects of reinforced patient education using a smartphone application software (APP) for colonoscopy preparation in participants in a CRC screening program. METHODS: We performed a prospective, endoscopist-blinded study of 500 patients undergoing split-dose bowel preparation for CRC screening or surveillance colonoscopies at multiple centers in Germany, from November 2017 through January 2019. Participants (n = 500) were given oral and written instructions during their initial appointment and then randomly assigned (1:1) to groups that received reinforced education starting 3 days before the colonoscopy (APP group) or no further education (controls). The primary outcome was quality of bowel preparation according to the Boston bowel preparation scale. Secondary outcomes included polyp and adenoma detection rates, compliance with low-fiber diet, split-dose laxative intake, perceived discomfort from the preparation procedure. RESULTS: The mean Boston bowel preparation scale score was significantly higher in the APP-group (7.6 ± 0.1) than in the control group (6.7 ± 0.1) (P < .0001). The percentage of patients with insufficient bowel preparation was significantly lower in the APP group (8%) than in the control group (17%) (P = .0023). The adenoma detection rate was significantly higher in the APP group (35% vs 27% in controls) (P = .0324). Use of the APP was accompanied by a lower level of non-compliance with correct laxative intake (P =.0080) and diet instructions (P = .0089). The APP group reported a lower level of discomfort during preparation (P < .0001). CONCLUSIONS: In a randomized trial, reinforcing patient education with a smartphone application optimized bowel preparation in the 3 days before colonoscopy, increasing bowel cleanliness, adenoma detection, and compliance in patients undergoing CRC screening or surveillance. ClinicalTrials.gov no: NCT03290157.