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Objective: The study investigates the prognostic impact of the severity and etiology of chronic kidney disease (CKD) in patients with heart failure with mildly reduced ejection fraction (HFmrEF)., Background: Data regarding the outcomes in patients with CKD in HFmrEF is scarce., Methods: Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Prognosis of patients with different stages and etiologies of CKD was investigated with regard to the primary endpoint of all-cause mortality at 30 months., Results: A total of 2155 consecutive patients with HFmrEF were included with an overall prevalence of CKD of 31%. Even milder stages of CKD (i.e., KDIGO stage 3a) were associated with an increased risk of 30-months all-cause mortality (HR = 1.242; 95% CI 1.147-1.346; p = 0.001). However, long-term prognosis did not differ in patients with KDIGO stage 5 compared to patients with stage 4 (HR = 0.886; 95% CI 0.616-1.275; p = 0.515). Furthermore, the highest risk of HF-related rehospitalization was observed in patients with KDIGO stages 3b and 4 (log rank p ≤ 0.015), whereas patients with KDIGO stage 5 had a lower risk of HF-related rehospitalization compared to patients with KDIGO stage 4 (HR = 0.440; 95% CI 0.228-0.849; p = 0.014). In contrast, the etiology of CKD was not associated with the risk of 30-month all-cause mortality (log rank p ≥ 0.347) and HF-related rehospitalization (log rank p ≥ 0.149)., Conclusion: In patients with HFmrEF, even milder stages of CKD were independently associated with increased risk of 30-months all-cause mortality., (© 2024. The Author(s).)

Background: Obesity is a known risk factor for cardiovascular disease (CVD), yet an 'obesity paradox' has been observed in various CVD contexts. The impact of obesity on heart failure (HF) patients treated with a wearable cardioverter-defibrillator (WCD) remains underexplored., Methods: In a multicentre international registry, we retrospectively collected data from a consecutive series of 1003 patients. These patients were divided into three body mass index (BMI) groups: <25 kg/m 2 (n = 348), 25-30 kg/m 2 (n = 383), and >30 kg/m 2 (n = 272), with BMI > 30 kg/m 2 defined as the reference category. Demographics, indications, adherence, WCD shocks, arrhythmic events, rehospitalization due to cardiovascular causes, and mortality were analysed., Results: At 3 month follow-up, patients with a BMI > 30 showed the greatest improvement in left ventricular ejection fraction (LVEF) at 51.4%, significantly higher than the 41.4% in those with a BMI < 25 (P = 0.017) and comparable with the 49.4% in the BMI 25-30 group (P = 0.635). WCD wearing time and adherence were similar across all BMI groups. The incidence of WCD shock was similar across BMI groups. Rates of ventricular tachycardia (VT), ventricular fibrillation and non-sustained VT (ns-VT) were comparable across BMI groups. The rate of implantable cardioverter-defibrillator (ICD) implantation was 40.3% across all patients, with a slightly lower rate in the BMI > 30 group (36.8%) compared with others, although not significantly. Rehospitalization due to cardiovascular causes was significantly lower in the BMI > 30 group (55.4%) compared with the BMI 25-30 group (70.9%; P = 0.048), but similar to the BMI < 25 group (54.9%; P = 0.957). At 2 year follow-up, mortality was lower in the BMI > 30 group (5.9%) compared with the BMI < 25 (7.5%; P = 0.029) and BMI 25-30 groups (7%; P = 0.681). In multivariable analysis, LVEF at long term was significantly associated with a reduction in mortality., Conclusions: Obese patients exhibited significantly greater improvement in LVEF, which was associated with reduced mortality. Adherence to WCD therapy was excellent across all BMI groups. ICD implantation occurred in 40.3% of patients, with similar WCD shock rates and arrhythmic events across BMI groups. An obesity paradox was observed, with obese patients demonstrating significantly lower rehospitalization rates due to cardiovascular causes and reduced mortality at follow-up., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: Evaluation of a kidney-adjusted enhanced recovery after surgery (ERAS ® ) protocol (kERAS) in patients undergoing nephron-sparing surgery (PN)., Methods: The kERAS protocol is a multidimensional protocol focusing on optimized perioperative fluid and nutrition management as well as strict intraoperative and postoperative blood pressure limits. It was applied in a prospective cohort (n = 147) of patients undergoing open or robotic PN. Patients were analyzed for the development of acute postoperative renal failure (AKI), achievement of TRIFECTA criteria, upstaging or new onset of chronic kidney disease (CKD) and length of hospital stay (LOS) and compared to a retrospective cohort (n = 162) without application of the protocol., Results: Cox regression analyses could not confirm a protective effect of kERAS on the development of AKI post-surgery. A positive effect was observed on TRIFECTA achievement (OR 2.2, 95% CI 1.0-4.5, p = 0.0374). Patients treated with the kERAS protocol showed less long-term CKD upstaging compared to those treated with the standard protocol (p = 0.0033). There was no significant effect on LOS and new onset of CKD., Conclusion: The implementation of a kERAS protocol can have a positive influence on long-term renal function in patients undergoing PN. It can be used safely without promoting AKI. Furthermore, it can be realized with a manageable amount of additional effort., (© 2024. The Author(s).)

Background: Acute cellular rejection (ACR) in heart transplant (HTx) recipients may be accompanied by cardiac cell damage with subsequent exposure to cardiac autoantigens and the production of cardiac autoantibodies (aABs). This study aimed to evaluate a peptide array screening approach for cardiac aABs in HTx recipients during ACR (ACR-HTx)., Methods: In this retrospective single-center observational study, sera from 37 HTx recipients, as well as age and sex-matched healthy subjects were screened for a total of 130 cardiac aABs of partially overlapping peptide sequences directed against structural proteins using a peptide array approach., Results: In ACR-HTx, troponin I (TnI) serum levels were found to be elevated. Here, we could identify aABs against beta-2-adrenergic receptor (β-2AR: EAINCYANETCCDFFTNQAY) to be upregulated in ACR-HTx (intensities: 0.80 versus 1.31, P = 0.0413). Likewise, patients positive for β-2AR aABs showed higher TnI serum levels during ACR compared with aAB negative patients (10.0 versus 30.0 ng/L, P = 0.0375). Surprisingly, aABs against a sequence of troponin I (TnI: QKIFDLRGKFKRPTLRRV) were found to be downregulated in ACR-HTx (intensities: 3.49 versus 1.13, P = 0.0025). A comparison in healthy subjects showed the same TnI sequence to be upregulated in non-ACR-HTx (intensities: 2.19 versus 3.49, P = 0.0205), whereas the majority of aABs were suppressed in non-ACR-HTx., Conclusions: Our study served as a feasibility analysis for a peptide array screening approach in HTx recipients during ACR and identified 2 different regulated aABs in ACR-HTx. Hence, further multicenter studies are needed to evaluate the prognostic implications of aAB testing and diagnostic or therapeutic consequences., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Adherence to follow-up (FU) care after bariatric surgery is poor despite strong recommendations. In our pilot Bella trial, we demonstrated that a completely remote follow-up program via smartphone is feasible and safe for patients after bariatric surgery. Building on this, we aim to verify our results in a multicenter, randomized controlled setting., Methods: This trial plans to enroll 410 participants undergoing primary bariatric surgery in seven German bariatric centers. Participants are randomized into two groups: a control group receiving in-person FU according to the standard in the bariatric centers, and an interventional group monitored using a smartphone application (app). The app sends standardized questionnaires and reminders regarding regular vitamin intake and exercises. The built-in messaging function enables patients to communicate remotely with medical care professionals. After one year, all participants are evaluated at their primary bariatric centers. The primary outcome is weight loss 12 months after surgery. The secondary outcomes include obesity-related comorbidities, quality of life, serum values of vitamins and minerals, body impedance analysis, visits to the emergency department or readmission, patient compliance, and medical staff workload., Discussion: The current study is the first prospective, individually randomized-controlled, multicenter trial where a mobile application completely replaces traditional in-person visits for post-bariatric surgery follow-ups in bariatric centers., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Despite mobilization is highly recommended in the ERAS ® colorectal guideline, studies suggest that more than half of patients don't reach the daily goal of 360 min out of bed. However, data used to quantify mobilization are predominantly based on self-assessments, for which the accuracy is uncertain. This study aims to accurately measure postoperative mobilization in ERAS ® -patients by validated motion data from body sensors., Methods: ERAS ® -patients with elective bowel resections were eligible. Self-assessments and motion sensors (movisens: ECG-Move 4 and Move 4; Garmin: Vivosmart4) were used to record mobilization parameter from surgery to postoperative day 3 (POD3): Time out of bed, time on feet and step count., Results: 97 patients were screened and 60 included for study participation. Self-assessment showed a median out of bed duration of 215 min/day (POD1: 135 min, POD2: 225 min, POD3: 225 min). The goal of 360 min was achieved by 16.67% at POD1, 21.28% at POD2 and 20.45% at POD3. Median time on feet objectively measured by Move 4 was 109 min/day. During self-assessment, patients significantly underestimated their "time on feet"-duration with 85 min/day (p = 0.008). Median number of steps was 933/day (Move 4)., Conclusion: This study confirmed with objectively supported data, that most patients don't reach the daily mobilization goal of 360 min despite being treated by an ERAS ® -pathway with ERAS ® -nurse. Even considering an empirically approximated underestimation, the ERAS ® -target isn't achieved by more than 75% of patients. Therefore, we propose an adjustment of the general ERAS ® -goals into more patient-centered, individualized and achievable goals., Registration: This study is part of the MINT-ERAS-project and was registered prospectively in the German Clinical Trials Register on 25.02.2022. Trial registration number is "DRKS00027863"., (© 2024. The Author(s).)

Purpose: To evaluate the influence of a previous caesarean section on adverse composite maternal and perinatal outcome in women who attempted a trial of labor., Methods: This historical cohort study analyzed maternal and perinatal outcome in women with otherwise low risk pregnancies at term who underwent a trial of labor after a caesarean section (TOLAC). The primary outcome measure was the adverse composite outcome. Secondary outcome measures were amongst others the caesarean section rate and the mode of vaginal delivery., Results: The adverse composite outcome was more frequently in the previous caesarean section group compared to women with no previous caesarean Sect. (22.3% vs. 15.6%, p < 0.0001). The percentage of caesarean Sect. (15.4% vs. 8.2%, p < 0,0001), uterine rupture (1.0% vs. 0.02%, p < 0.0001), placental abruption (1.1% vs. 0.3%, p = 0.0014), vaginal operative delivery (16.0% vs. 8.6%, p < 0.0001), pH < 7.10 (3.7% vs. 2.5%, p = 0.0151), base excess < -12 (3.2% vs. 2.2%, p = 0.0297), abnormal cardiotocography (22.5% vs. 13.9%, p < 0,0001) and fetal blood analysis (6.2% vs. 2.6%, p < 0.0001) was significantly higher in women with a previous caesarean section. Taking the parity into account, these differences could only been seen in women without a previous vaginal delivery. In parous women with a previous vaginal delivery and a caesarean section in history, the adverse composite did not differ between the groups. Only the rate of pH < 7.1 was higher in women after a caesarean Sect. (4.5% vs. 1.8%, p = 0.0436)., Conclusion: Trial of labor after caesarean in otherwise low risk pregnancies is associated with a higher rate of complications especially if there is no history of vaginal delivery., (© 2024. The Author(s).)

Aims: The study sought to comprehensively investigate the effect of heart failure (HF) pharmacotherapies in patients with HF with mildly reduced ejection fraction (HFmrEF). In the absence of randomized controlled trials, guideline recommendations concerning HF-related therapies in patients with HFmrEF are limited., Methods and Results: Consecutive patients hospitalized with HFmrEF were retrospectively included at one institution from 2016 to 2022. The prognostic value of treatment with beta-blockers (BB), angiotensin-converting enzyme inhibitors, receptor blockers, or receptor-neprilysin inhibitor (ACEi/ARB/ARNI), mineralocorticoid receptor antagonists (MRA), and sodium-glucose-linked transport protein 2 inhibitors (SGLT2i) was investigated for all-cause mortality at 30 months (a median follow-up) and HF-related rehospitalization. A total of 2109 patients with HFmrEF were included. Treatment with BB [27.0 vs. 35.0%; hazard ratio (HR) = 0.737; 95% confidence interval (CI) 0.617-0.881; P = 0.001], ACEi/ARB/ARNI (25.9 vs. 37.6%; HR = 0.612; 95% CI 0.517-0.725; P = 0.001), and SGLT2i (11.9 vs. 29.5%; HR = 0.441; 95% CI 0.236-0.824; P = 0.010) was associated with a lower risk of 30-month all-cause mortality, which was still demonstrated after multivariable adjustment and propensity score matching. In contrast, MRA treatment was not associated with long-term prognosis. The risk of HF-related rehospitalization was not affected by HF pharmacotherapies. Finally, the lowest risk of long-term all-cause mortality was observed in patients with combined use of BB, ACEi/ARB/ARNI, and SGLT2i (HR = 0.456; 95% CI 0.227-0.916; P = 0.027)., Conclusion: Beta-blockers, ACEi/ARB/ARNI, and SGLT2i were independently associated with a lower risk of all-cause mortality in patients with HFmrEF, specifically when applied as combined 'HF triple therapy'. Randomized studies are needed to investigate the effect of HF-related pharmacotherapies in patients with HFmrEF., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Mild breast swelling is frequently observed in newborns during the first postnatal week. Breast enlargement is also observed in a minor proportion of infants beyond the first postnatal week, leading to discussions how to deal with it. Our objective was to review a case series of infants with prolonged breast swelling., Case Presentation: We examined five infants with pronounced breast enlargement beyond the first postnatal week and measured human chorionic gonadotropin (HCG), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and progesterone (P4) in blood samples and analyzed breast volume by sonographic volume determination in all infants initially and across time. The regression of breast enlargement positively correlated with serum prolactin levels in infants with breast enlargement beyond the first week of life. Complete regression occurred after several weeks and was characterized by normalization of serum prolactin levels., Conclusions: The present study emphasizes the role of prolactin in neonates with pronounced breast enlargement beyond the first week of life., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: The present study aims to clarify the prevalence and prognostic impact of anaemia and iron deficiency in patients with heart failure with mildly reduced ejection fraction (HFmrEF)., Background: The prognostic impact of anaemia and iron deficiency in HFmrEF has not yet been clarified., Methods: Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Patients with anaemia (i.e. haemoglobin <13 g/dL in males and < 12 g/dL in females) were compared to patients without, respectively patients with or without iron deficiency. The primary endpoint was all-cause mortality at 30 months (median follow-up), secondary endpoints comprised HF-related rehospitalisation., Results: Two thousand one hundred and fifty four patients with HFmrEF with a median haemoglobin level of 12.2 g/dL were included. Anaemia was present in 52% of patients with HFmrEF and associated with a higher risk of all-cause mortality (44% vs. 18%; HR = 3.021; 95% CI 2.552-3.576; p =.001) and HF-related rehospitalisation (18% vs. 8%; HR = 2.351; 95% CI 1.819-3.040; p =.001) at 30 months, which was confirmed after multivariable adjustment. Although iron status was infrequently assessed in anaemics with HFmrEF (27%), the presence of iron deficiency was associated with higher risk of rehospitalisation for worsening HF (25% vs. 15%; HR = 1.746; 95% CI 1.024-2.976; p =.038), but not all-cause mortality (p =.279) at 30 months., Conclusion: Anaemia and iron deficiency are very common in atleast half of patients with HFmrEF and independently associated with adverse long-term prognosis., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background:  With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Accurate and rapid determination of DOAC levels would guide medical decision-making to (1) determine the potential contribution of the DOAC to spontaneous or trauma-induced hemorrhage; (2) identify appropriate candidates for reversal, or (3) optimize the timing of urgent surgery or intervention., Methods and Results:  The DOAC Dipstick test uses a disposable strip to identify factor Xa- or thrombin inhibitors in a urine sample. Based on the results of a systematic literature search followed by an analysis of a simple pooling of five retrieved clinical studies, the test strip has a high sensitivity and an acceptably high negative predictive value when compared with levels measured with liquid chromatography tandem mass spectrometry or calibrated chromogenic assays to reliably exclude plasma DOAC concentrations ≥30 ng/mL., Conclusion:  Based on these data, a simple algorithm is proposed to enhance medical decision-making in acute care indications useful primarily in hospitals not having readily available quantitative tests and 24/7. This algorithm not only determines DOAC exposure but also differentiates between factor Xa and thrombin inhibitors to better guide clinical management., Competing Interests: J.H. is general manager and founder of DOASENSE GmbH, J.D. is CEO of Qualiblood SA. All other authors declare no conflicts of interest., (Thieme. All rights reserved.)

This study investigated whether adjuvant treatments in stage III cutaneous melanoma (CM) influenced patterns of recurrence. Patients with primary (n = 1033) or relapsed CM (n = 350) who received adjuvant therapies with Nivolumab (N), Pembrolizumab (P), or Dabrafenib and Trametinib (D + T) were extracted from the prospective multicenter real-world skin cancer registry ADOReg. Endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), organ-specific DMFS, and overall survival (OS). For primary cases, D + T indicated an improved PFS (1- and 2-year PFS: 90.9%; 82.7%) as compared to P (81.0%, 73.9%; p = .0208), or N (83.8%, 75.2%; p = .0539). BRAF-mutated(mut) CM demonstrated significantly lower PFS (p = .0022) and decreased DMFS (p = .0580) when treated with immune checkpoint inhibitor (ICI) instead of D + T. Besides, NRAS-mut CM tended to perform worse than wt CM upon ICI (PFS: p = .1349; DMFS: p = .0540). OS was similar between the groups. Relapsed cases showed decreased PFS, DMFS, and OS in comparison to primary (all: p < .001), without significant differences between the subgroups. Organ-specific DMFS was significantly altered for primary cases with bone (p = .0367) or brain metastases (p = .0202). In relapsed CM, the frequency of liver (D + T: 1.5%; P: 12%; N: 9%) and LN metastases (D + T: 1.5%; P: 12%; N: 10.2%) was significantly lower with adjuvant D + T than ICI. NRAS-mut CM showed increased recurrence in primary and relapsed cases. These data show that adjuvant D + T is superior to ICI in primary BRAF-mut CM., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: The prevalence of peripheral arterial disease and the number of revascularization procedures performed in symptomatic patients are steadily increasing. However, uncertainties remain regarding hemodynamic monitoring after revascularization and the prediction of clinical outcomes. This study aimed to investigate hemodynamic parameters with a focus on the microvasculature. Methods: This prospective, single-center study included 29 patients (15 with intermittent claudication [IC] and 14 with chronic limb-threatening ischemia [CLTI]). Before and after the revascularization procedure, in addition to the ankle-brachial index (ABI), microperfusion parameters, including microvascular blood flow, capillary oxygen saturation (SO 2 ), and relative hemoglobin content (rHb), were assessed with lightguide spectrophotometry combined with laser Doppler flowmetry using an oxygen-to-see (O2C) device in the horizontal and elevated leg positions. Results: At baseline, SO 2 in the elevated leg position was significantly lower in patients with CLTI than in those with IC ( p = 0.0189), whereas the other microcirculatory parameters and ABI values were not significantly different. Patients with diabetes mellitus had a higher flow rate than those without in the horizontal leg position ( p = 0.0162) but not in the elevated leg position. After successful revascularization, the flow increased immediately and significantly in both positions, whereas SO 2 , rHb, and the ABI did not. Conclusions: Elevated leg SO 2 was significantly lower in CLTI than in clinically compensated peripheral arterial disease, whereas microvascular flow was a suitable surrogate parameter indicating successful revascularization. In studies using surgical or interventional revascularization procedures, noninvasive hemodynamic monitoring of the microcirculation at the foot level might be beneficial.

Background & Aims: Exploration whether Motivational Interviewing (MI) could be learned and implemented with ease within a surgical in-hospital setting and whether participation in the intervention led to significantly higher compliance with ERAS®-recommended protein intake goals. The individual healing process of many patients is delayed because they fail to cover their calorie requirement, which could be counteracted by a patient-centered conversational intervention that is new in perioperative practice., Methods: This patient-blinded pilot-RCT included 60 patients (≥18 years) following the certified ERAS® bowel protocol for colorectal surgery between March and August 2022. Five perioperative MI interventions were conducted by two health employees certified to perform MI. Key endpoints were the number of protein shakes drunk, calories of proteins ingested and overall calorie intake., Results: A total of 60 patients (34 men [56.7%]; mean [SD] age, 60.7 [13.3] years) were randomized. MI patient-group had significantly higher protein shake intake on all postoperative days except day 3. For days 0-3 MI group drank significantly more shakes overall (median 5.5 vs. 2.0; P = 0.004) and consumed more calories (median 1650.0 vs. 600.0 kcal; P = 0.004) and proteins (median 110.0 vs. 40.0 g; P = 0.005). Total calorie intake for each day by shakes and dietary intake was significantly higher in the MI-intervention group on day 2 (mean 1772.3 vs. 1358.9 kcal; P = 0.03)., Conclusions: MI may contribute to improve compliance with nutritional goals in the certified ERAS® protocol by increasing protein and calorie intake. The findings suggest further investigation of MI to help patients achieve their perioperative nutrition goals in different clinical settings., Trial Registration: DRKS - Deutsches Register Klinischer Studien; DRKS-ID: DRKS00027863; https://drks.de/search/de/trial/DRKS00027863., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported by the authors., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Listing tools have been developed to improve medications in older patients, including the Fit fOR The Aged (FORTA) list, a clinically validated, positive-negative list of medication appropriateness. Here, we aim to validate MyFORTA, an automated tool for individualized application of the FORTA list., Methods: 331 participants of a multi-center cohort study (AgeCoDe) for whom the FORTA score (sum of overtreatment and undertreatment errors) had been determined manually (gold standard [GS]) were reassessed using the automated MyFORTA (MF) tool. This tool determines the score from ATC and ICD codes combined with clinical parameters., Results: The FORTA scores were 9.01 ± 2.91 (mean ± SD, MF) versus 6.02 ± 2.52 (GS) (p < 0.00001). Removing undertreatment errors for calcium/vitamin D (controversial guidelines) and influenza/pneumococcal vaccinations (no robust information in the database), the difference decreased: 7.5 ± 2.7 (MF) versus 5.98 ± 2.55 (GS) (p < 0.00001). The remaining difference was driven by, for example, missing nitro spray in coronary heart disease/acute coronary syndrome as the related information was rarely found in the database, but notoriously detected by MF. Three hundred and forty errors from those 100 patients with the largest score deviation accounted for 68% of excess errors by MF., Conclusion: MF was more sensitive to detect medication errors than GS, all frequent errors only detected by MF were plausible, and almost no adaptations of the MF algorithm seem indicated. This automated tool to check medication appropriateness according to the FORTA list is now validated and represents the first clinically directed algorithm in this context. It should ease the application of FORTA and help to implement the proven beneficial effects of FORTA on clinical endpoints., (© 2024. The Author(s).)

Study Design: Very few studies exist regarding the fracture pattern variability of the zygomaticoorbital (ZMO) complex. The retrospective evaluation of a large series of surgically treated unilateral ZMO fractures would in certain circumstances help intraoperative predictability and define sensitive indicators for open reduction and internal fixation., Objective: The aim of this study was to investigate the different fracture patterns after ZMO complex injury regarding the 5 anatomic sutures of the zygoma as well as the concomitance of the paranasal buttress and maxillary sinus wall fracture., Methods: The medical records of all patients with unilateral ZMO fractures who underwent surgical intervention in a single trauma center department between April 2015 and June 2020 were retrospectively reviewed. Demographic and anamnesis data, radiologic findings, and surgical reports were evaluated. According to the preoperative radiologic evaluation, ZMO fractures were classified as unisutural, bisutural, trisutural, tetrasutural, and complete based on the number of zygomatic sutures. The prevalence of various fracture patterns was analyzed. The impact of patient's age and trauma etiology on the fracture pattern was evaluated using descriptive statistical analysis., Results: The study included 492 patients with unilateral ZMO fractures, with a mean age of 49.93 years (SD = 20.66) and a male:female ratio of 2.23:1. The most affected age group was 19-44 years (41.67%) and tripping falls were the most common etiology (27.24%). Trisutural (57.32%) and unisutural fractures (23.17%) were the most common, followed by tetrasutural (8.94%), bisutural (8.54%), and complete fractures (2.03%). A trisutural fracture involving the zygomaticomaxillary suture, the infraorbital rim, and the zygomaticosphenoidal suture was the most common fracture pattern (52.03%). Most fractures were observed in the zygomaticosphenoidal suture (86.99%), followed by the infraorbital rim (74.59%) and the zygomaticomaxillary suture (68.29%). Fractures of the maxillary sinus wall and the paranasal buttress co-existed in 9.55% and 31.30% of all cases, respectively. No correlation was detected between age and fracture pattern ( P = .4111). Tripping falls and bicycle accidents significantly influenced the fracture pattern ( P < .0001)., Conclusions: According to the results, knowledge of the fracture pattern variability of the ZMO complex could in certain circumstances designate CT or CBCT as mandatory before operating on ZMO fractures. Consequently, unnecessary incisions could be avoided. The high concomitance of paranasal buttress fracture also suggests its intraoperative surgical exploration. Further studies should correlate the clinical findings with indication for surgery and postoperative outcome for the different fracture patterns described., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1-120, 20.4% dropped out), with a median age of 61 years (range 30-90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation.

Inhibitors of anti-apoptotic BCL-2 family proteins in combination with chemotherapy and hypomethylating agents (HMA) are promising therapeutic approaches in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). Alvocidib, a cyclin-dependent kinase 9 (CDK9) inhibitor and indirect transcriptional repressor of the anti-apoptotic factor MCL-1, has previously shown clinical activity in AML. Availability of biomarkers for response to the alvocidib + 5-azacytidine (5-AZA) could also extend the rationale of this treatment concept to high-risk MDS. In this study, we performed a comprehensive in vitro assessment of alvocidib and 5-AZA effects in N=45 high-risk MDS patients. Our data revealed additive cytotoxic effects of the combination treatment. Mutational profiling of MDS samples identified ASXL1 mutations as predictors of response. Further, increased response rates were associated with higher gene expression of the pro-apoptotic factor NOXA in ASXL1-mutated samples. The higher sensitivity of ASXL1 mutant cells to the combination treatment was confirmed in vivo in ASXL1Y588X transgenic mice. Overall, our study demonstrated augmented activity for the alvocidib + 5-AZA combination in higher-risk MDS and identified ASXL1 mutations as a biomarker of response for potential stratification studies.

Purpose: Early mobilization is an essential component of the Enhanced Recovery after Surgery (ERAS®)-pathway. However, a large percentage of patients fail to achieve the ERAS® recommended goal (360 min out of bed from post-operative day 1/POD1). Motivational Interviewing (MI) is an evidence-based type of patient-centered consultation to promote intrinsic motivation. This study aims to evaluate if MI can improve postoperative mobilization., Methods: This two-arm, patient-blinded pilot randomized controlled trial included ERAS®-patients undergoing elective bowel resections. Conversations were validated by MI Treatment Integrity. Two validated motion sensors (movisens) and self-assessments were used to measure mobilization (POD1-POD3: Time out of bed, time on feet and step count)., Results: 97 patients were screened, 60 finally included and randomized. Cumulatively across POD1-3, the intervention group (IG) was longer out of bed than the control group (CG) (median: 685 vs. 420 min; p=0.022). The IG achieved the ERAS®-goal of 360 min/day more frequently across POD1-3 (27.4% vs. 10.61%; p=0.013). Time on feet was 131.5 min/day (median per POD) in IG vs. 95.8 min/day in the CG (p=0.212), step count was 1347 in IG vs. 754 steps/day in CG (p=0.298)., Conclusion: MI could be conducted low threshold and was well accepted by patients. MI can improve mobilization in the context of ERAS®. Despite better performance, it should be noted that only 27.4% of the IG reached the ERAS®-compliance goal of 360 min/day. The findings of this pilot study stipulate to further test the promising perioperative effects of MI within a multicenter superiority trial., Registration: This study was registered prospectively in the German Clinical Trials Register on 25.02.2022. Trial registration number is "DRKS00027863"., (© 2024. The Author(s).)

Purpose: The aim of this study is to identify pre- and intraoperative factors indicating the feasibility of intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS)., Materials and Methods: From January 2018 to December 2019, a total of 128 women undergoing BCS due to early breast cancer were included in this prospective observational study, independent of whether IORT was planned or not. Patient and tumor characteristics as well as surgical parameters that could potentially influence the feasibility of IORT were recorded for the entire collective. In addition, a preoperative senological assessment was performed and analyzed to assess the feasibility of IORT. Logistic regression was then used to identify relevant preoperative parameters and to generate a formula predicting the feasibility of IORT., Results: Of the 128 included women undergoing BCS, 46 were preoperatively rated to be feasible, 20 to be questionably feasible for IORT. Ultimately, IORT was realized in 30 patients. The most frequent reasons for omission of IORT were insufficient tumor-to-skin distance and/or an excessively large tumor cavity. Small clinical tumor size and large tumor-to-skin distance according to preoperative ultrasound were significantly related to accomplishment of IORT., Conclusion: We observed that preoperative ultrasound-based tumor-skin distance is a significant factor in addition to already known parameters to predict feasibility of IORT. Based on our findings we developed a formula to optimize IORT planning which might serve as an additional tool to improve patient selection for IORT in early breast cancer., (© 2023. The Author(s).)

Background: A therapeutic effect of sacral neuromodulation (SNM) on fecal incontinence (FI) and quality of life has been proven in adults. SNM is, however, rarely used in pediatric cases. The aim of the study is to investigate effects of SNM in pediatric constipation in a prospective parallel-group trial., Methods: A monocentric, randomized, unblinded, parallel-group trial is conducted. SNM is conducted in the invasive variant and in an innovative, external approach with adhesive electrodes (enteral neuromodulation, ENM). We include patients with constipation according to the ROME IV criteria and refractory to conventional options. Patients with functional constipation and Hirschsprung's disease are able to participate. Participants are allocated in a 1:1 ratio to either SNM or ENM group. Clinical data and quality of life is evaluated in regular check-ups. Neuromodulation is applied continuously for 3 months (end point of the study) with follow-up-points at 6 and 12 months. Findings are analyzed statistically considering a 5% significance level (p ≤ 0.05). Outcome variables are defined as change in (1) episodes of abdominal pain, (2) episodes of FI, (3) defecation frequency, (4) stool consistency. Improvement of proprioception, influence on urinary incontinence, quality of life and safety of treatment are assessed as secondary outcome variables. We expect a relevant improvement in both study groups., Discussion: This is the first trial, evaluating effects of neuromodulation for constipation in children and adolescents and comparing effects of the invasive and non-invasive application (SNM vs. ENM)., Trial Registration: The study is registered with clinicaltrials.gov, Identifier NCT04713085 (date of registration 01/14/2021)., (© 2024. The Author(s).)

Aim: The aim of this study was to investigate perinatal outcome in singleton pregnancies at term with isolated oligohydramnios, diagnosed by using the single deepest pocket method., Patients and Methods: In this historic cohort study, the perinatal outcomes of 196 women with isolated oligohydramnios at term, diagnosed by using the single deepest pocket method, were compared to 8,676 women with normal amniotic fluid volume. The primary outcome measure was the Cesarean section rate. Further outcome parameters included the rate of induction of labor, abnormal cardiotocography, umbilical cord pH and base excess, Apgar, meconium-stained liquor and admission to neonatal intensive care unit., Results: In the group with isolated oligohydramnios, there were significantly more Cesarean sections (p=0.0081) and more abnormal cardiotocographies (p=0.0005). Univariate and multivariate analyses showed that this difference was seen particularly in nulliparous women (p=0.0025 for Cesarean section and 0.0368 for abnormal cardiotocography). Peripartal and perinatal outcome parameters were not different between the two groups., Conclusion: In women with isolated oligohydramnios at term, there is no impact on fetal outcome. The influence of isolated oligohydramnios on the rate of cesarean section and abnormal cardiotocography is considered to be less than that of parity., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: Perforation of esophagus or stomach is a potential complication during and after insertion of a gastric tube in neonates. The aim of this study was to analyze different types of gastric tubes in a three-dimensional (3D) model of neonatal esophagus and stomach regarding potential perforations., Methods: A 3D model of esophagus and stomach was created based on computed tomography data of a term neonate. Three types of gastric tubes were inserted into the 3D model, the localization was examined by radioscopy and the behavior, stiffness and manageability of each gastric tube was evaluated., Results: Insertion of gastric tubes with higher stiffness was easier. The rates of correct localization differed significantly between the gastric tubes with the highest rate of correct localization in the softest tube (48.5%) and the lowest rate in the tube with the highest stiffness (21.2%). Additionally, the softest tube showed the lowest rate of localization of its tip at the stomach wall., Conclusions: The study illustrates differences between various types of gastric tubes regarding stiffness, behavior and resiliency. Softer gastric tubes may be beneficial. These differences may be relevant in neonatal care of very immature and very sick infants., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aims: This study sought to determine the prognostic impact of acute decompensated heart failure (ADHF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). ADHF is a major complication in patients with heart failure (HF). However, the prognostic impact of ADHF in patients with HFmrEF has not yet been clarified., Methods and Results: Consecutive patients hospitalized with HFmrEF (i.e. left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. The prognosis of patients with ADHF was compared with those without (i.e. non-ADHF). The primary endpoint was long-term all-cause mortality. Secondary endpoints included in-hospital all-cause mortality and long-term HF-related re-hospitalization. Kaplan-Meier, multivariable Cox proportional regression, and propensity score matched analyses were performed for statistics. Long-term follow-up was set at 30 months. A total of 2184 patients with HFmrEF were included, ADHF was present in 22%. The primary endpoint was higher in ADHF compared to non-ADHF patients with HFmrEF [50% vs. 26%; hazard ratio (HR) = 2.269; 95% confidence interval (CI) 1.939-2.656; P = 0.001]. Accordingly, the secondary endpoint of long-term HF-related re-hospitalization was significantly higher (27% vs. 10%; HR = 3.250; 95% CI 2.565-4.118; P = 0.001). A history of previous ADHF before the index hospitalization was associated with higher rates of long-term HF-related re-hospitalization (42% vs. 23%; HR = 2.073; 95% CI 1.420-3.027; P = 0.001), but not with long-term all-cause mortality (P = 0.264)., Conclusion: ADHF is a common finding in patients with HFmrEF associated with an adverse impact on long-term prognosis., Competing Interests: Conflict of interest: The authors declare that they do not have any conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The primary aim was to compare the prevalence of acute and delayed intracranial haemorrhage (ICH) following mild traumatic brain injury (mTBI) in patients on antithrombotic medication referred to a clinic for oral and plastic maxillofacial surgery. The secondary aim was to evaluate the need for short-term hospitalisation based on initial radiological and clinical findings., Methods: This was an observational retrospective single-centre study of all patients on antithrombotic medication who were admitted to our department of oral and plastic maxillofacial surgery with mTBI over a 5 year period. Demographic and anamnesis data, injury characteristics, antithrombotic medication, radiological findings, treatment, and outcome were analysed. Patients were divided into the following four groups based on their antithrombotic medication: (1) single antiplatelet users, (2) vitamin K antagonist users, (3) direct oral anticoagulant users, and (4) double antithrombotic users. All patients underwent an emergency cranial CT (CT0) at admission. Based on clinical and radiological evaluation, different treatment protocols were applied. Patients with positive CT0 findings and patients with secondary neurological deterioration received a control CT (CT1) before discharge. Acute and delayed ICH and patient's outcome during hospitalisation were evaluated using descriptive statistical analysis., Results: A total of 696 patients (mean age, 71.6 years) on antithrombotic medication who presented at our department with mTBI were included in the analysis. Most injuries were caused by a ground-level fall (76.9%). Thirty-six patients (5.1%) developed an acute traumatic ICH, and 47 intracerebral lesions were detected by radiology-most of these in patients taking acetylsalicylic acid. No association was detected between ICH and antithrombotic medication (p = 0.4353). In total, 258 (37.1%) patients were admitted for 48 h in-hospital observation. The prevalence of delayed ICH was 0.1%, and the mortality rate was 0.1%. Multivariable analysis identified a Glasgow Coma Scale (GCS) of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea as clinical characteristics significantly associated with an increased risk of acute ICH, whereas age, sex, and trauma mechanism were not associated with ICH prevalence. Of the 39 patients who underwent a control CT1, most had a decreasing or at least constant intracranial lesion; in three patients, intracranial bleeding increased but was not clinically relevant., Conclusion: According to our experience, antithrombotic therapy does not increase the rate of ICH after mTBI. A GCS of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea are indicators of higher ICH risk. A second CT scan is more effective in patients with secondary neurological deterioration. Initial CT findings were not clinically relevant and should not indicate in-hospital observation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose:  Analysis of clinical and diagnostic findings in rare urogenital and perineal vascular malformations only occurring in 2-3 % of vascular anomalies with regard to clinical symptoms and treatment decisions., Materials and Methods:  All 25 out of 537 patients presenting with congenital urogenital and perineal vascular malformations at our institution from 2014 to 2021 were included. Vascular anomaly classification, anatomical location, clinical symptoms at presentation, diagnostic imaging, and pain intensity were retrospectively assessed from the patient record and therapy management was evaluated., Results:  In total, 25 patients (10 females (40 %), 15 males (60 %)), aged 6 to 77 years were included. Diagnoses were: 10 (40 %) venous malformations (VMs), 5 (20 %) lymphatic malformations (LMs) and 10 (40 %) arteriovenous malformations (AVMs). Malformation manifestations were: 12 (32 %) lesser pelvis, 12 (32 %) external genitalia, and 13 (34 %) perineal/gluteal region. One AVM was located in the kidney. The leading clinical symptom was pain. The mean intensity was 6.0/10 for LM, 5.7/10 for VM, and 4.5/10 for AVM. Further major symptoms included physical impairment, local swelling, and skin discoloration. Bleeding complications or sexual dysfunction were rare findings. Patients with VM reported significantly more symptoms than patients with AVM (p = 0.0129). In 13 patients (52 %) minimally invasive therapy was indicated: 10 (77 %) sclerotherapies and 3 (23 %) transcatheter embolization procedures. Complete symptomatic remission was achieved in 9 (69 %) patients, partial response in 3 (23 %) patients, and 1 patient showed no clinical response to therapy. Follow-up appointments without the need for immediate minimally invasive therapy were significantly more common in patients with AVMs than in patients with VMs (p = 0.0198)., Conclusion:  To create a higher awareness of congenital urogenital and perineal vascular malformations. Awareness of this rare condition avoids misdiagnosis. Therapy decisions should be symptom-oriented. Emergency intervention is rarely required, even in fast-flow vascular malformations., Key Points:   · Venous malformations cause more symptoms with higher pain intensity than arteriovenous malformations.. · Diagnosis and adequate treatment can be hampered by a lack of awareness of the clinical presentation.. · Bleeding complications are rare, even in high-flow vascular malformations.. · Pain and physical impairment are the most commonly observed symptoms in these patients.., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Manipulation of the subcellular localization of transcription factors by preventing their shuttling via the nuclear pore complex (NPC) emerges as a novel therapeutic strategy against cancer. One transmembrane component of the NPC is POM121, encoded by a tandem gene locus POM121A/C on chromosome 7. Overexpression of POM121 is associated with metabolic diseases (e.g., diabetes) and unfavorable clinical outcome in patients with colorectal cancer (CRC). Peroxisome proliferator-activated receptor-gamma (PPARγ) is a transcription factor with anti-diabetic and anti-tumoral efficacy. It is inhibited by export from the nucleus to the cytosol via the RAS-RAF-MEK1/2-ERK1/2 signaling pathway, a major oncogenic driver of CRC. We therefore hypothesized that POM121 participates in the transport of PPARγ across the NPC to regulate its transcriptional activity on genes involved in metabolic and tumor control. We found that POM121A/C mRNA was enriched and POM121 protein co-expressed with PPARγ in tissues from CRC patients conferring poor prognosis. Its interactome was predicted to include proteins responsible for tumor metabolism and immunity, and in-silico modeling provided insights into potential 3D structures of POM121. A peptide region downstream of the nuclear localization sequence (NLS) of POM121 was identified as a cytoplasmic interactor of PPARγ. POM121 positivity correlated with the cytoplasmic localization of PPARγ in patients with KRAS mutant CRC. In contrast, POM121A/C silencing by CRISPR/Cas9 sgRNA or siRNA enforced nuclear accumulation of PPARγ and activated PPARγ target genes promoting lipid metabolism and cell cycle arrest resulting in reduced proliferation of human CRC cells. Our data suggest the POM121-PPARγ axis as a potential drugable target in CRC., (© 2024. The Author(s).)

Objective: Fetal magnetic resonance imaging (MRI) is broadly used as a method for assessing prognosis in congenital diaphragmatic hernia (CDH). In addition to the extent of lung hypoplasia, determined by measuring the lung volume, cardiac impairment due to pulmonary hypertension and left cardiac hypoplasia is decisive for the prognosis. The percentage area of left ventricle (pALV) describes the percentage of the inner area of the left ventricle in relation to the total area, whereas the mediastinal shift angle (MSA) quantifies the extent of cardiac displacement. The prognostic value of pALV and MSA should be evaluated in terms of survival, the need for extracorporeal membrane oxygenation (ECMO) therapy, and the development of chronic lung disease (CLD)., Methods: In a total of 122 fetal MRIs, the MSA and pALV were measured retrospectively and complete outcome parameters were determined regarding survival for all 122 subjects, regarding ECMO therapy in 109 cases and about the development of CLD in 78 cases. The prognostic value regarding the endpoints was evaluated using logistic regression and ROC analysis., Results: The MSA was significantly higher in children who received ECMO therapy ( p = 0.0054), as well as in children who developed CLD ( p = 0.0018). ROC analysis showed an AUC of 0.68 for ECMO requirement and 0.77 with respect to CLD development. The pALV showed a tendency towards higher levels in children who received ECMO therapy ( p = 0.0824). The MSA and the pALV had no significant effect on survival (MSA: p = 0.4293, AUC = 0.56; pALV: p = 0.1134, AUC = 0.57)., Conclusions: The MSA determined in fetal MRI is a suitable prognostic parameter for ECMO requirement and CLD development in CDH patients and can possibly be used as a supplement to the established parameters.

Background: Vascular malformations are rare diseases that should be treated in dedicated vascular anomaly centers (VAC). There is only a small amount of data on the diagnostic and therapeutic handling of these patients, before they are referred to a VAC., Purpose: To demonstrate the disease-specific patient characteristics in a German VAC, which are required to determine diagnostic and therapeutic steps., Material and Methods: In a retrospective study, all patients who were treated in the VAC from April 2014 until August 2021 were identified. In total, 593 patients were included in this study., Results: Almost all patients had previously consulted a physician (591/593, 99.7%). A mean of two different physicians had been consulted (range 0-10). Patients with more complex, syndromal vascular malformations had significantly more previous appointments ( P  = 0.0018). In only 44% (261/593) of patients, the referral diagnosis was made correctly. Most patients had been previously treated for their vascular anomaly: pharmacotherapy (n = 130; 21.9%), compression garments (n = 141; 23.8%), surgical resection (n = 80; 17.3%) and sclerotherapy (n = 68; 11.5%). Fifty-two patients who had been falsely diagnosed had also received therapy prior to their referral to the VAC (8.8%). Most patients received an ultrasound examination in the VAC (n = 464; 78.2%). Most frequently, compression therapy was prescribed (n = 256; 43.2%), followed by sclerotherapy (n = 175, 29.5%) and pharmacotherapy (n = 55; 9.3%)., Conclusion: Patients suffering from vascular anomalies often go through a complicated scheduling with numerous outpatient appointments and have a high risk of misdiagnosis and mistreatment prolonging the medical condition. Therefore, patients with vascular anomalies should be treated in a dedicated vascular anomaly center., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The spectrum of patients with cardiogenic shock (CS) has changed significantly over time. CS has become especially more common in the absence of acute myocardial infarction (AMI), while this subset of patients was typically excluded from recent studies. Furthermore the prognostic impact of onset time and onset place due to CS has rarely been investigated., Research Question: Do the place of CS onset (out-of-hospital, ie, primary CS vs in-hospital, ie, secondary CS) and the onset time of out-of-hospital CS (ie, on-hours vs off-hours admission) affect the risk of all-cause mortality at 30 days?, Study Design and Methods: This prospective monocentric registry included consecutive patients with CS of any cause from 2019 until 2021. First, the prognostic impact of the place of CS onset (out-of-hospital, ie, primary CS vs during hospitalization, ie, secondary CS) was investigated. Thereafter, the prognostic impact of the onset time of out-of-hospital CS was investigated. Furthermore, the prognostic impact of causative AMI vs non-AMI was investigated. Statistical analyses included Kaplan-Meier analyses, and univariable and multivariable Cox regression analyses., Results: Two hundred seventy-three patients with CS were included prospectively (64% with primary out-of-hospital CS). The place of CS onset was not associated with increased risk of all-cause mortality within the entire study cohort (secondary in-hospital CS: hazard ratio [HR], 1.532; 95% CI, 0.990-2.371; P = .06). However, increased risk of 30-day all-cause mortality was seen in patients with AMI related secondary in-hospital CS (HR, 2.087; 95% CI, 1.126-3.868; P = .02). Furthermore, primary out-of-hospital CS admitted during off-hours was associated with lower risk of all-cause mortality compared to primary CS admitted during on-hours (HR, 0.497; 95% CI, 0.302-0.817; P = .01), irrespective of the presence or absence of AMI., Interpretation: Primary and secondary CS were associated with comparable, whereas primary out-of-hospital CS admitted during off-hours was associated with lower risk of all-cause mortality at 30 days., Trial Registry: ClinicalTrials.gov; No.: NCT05575856; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Traumatic subdiaphramatic perforation of esophagus or stomach in neonates represents a rare clinical complication following the insertion of a gastric tube and is associated with high morbidity and mortality. The aim of the present study was to evaluate whether the angle of the gastric tube depicted on a plain radiograph may serve as a diagnostic tool to predict subdiaphragmatic traumatic (or iatrogenic) perforation., Patients and Methods: Thoraco-abdominal radiographs of 128 preterm and term neonates without perforation and 15 neonates with perforation of the esophagogastric junction or the stomach were retrospectively analysed., Results: The angle of the gastric tube increases with postnatal age (p=0.0380). In the control group, the angle of the gastric tube varied between 13° and 48° (median: 31°), whereas the values ranged from -31° to 42° (median: 11°) in neonates with subdiaphragmatic perforation. Perforation should thus be suspected in cases with an angle of<20° (sensitivity: 93.3%; specificity: 91.4%). Moreover, an unusual localization of the tip beyond the gastric bubble is highly indicative of perforation., Discussion: The present study emphasizes the importance of verifying the correct course of an inserted gastric tube., Conclusions: In daily clinical practice, an angle of<20° should be followed by thorough physical examination, abdominal ultrasound and if applicable contrast medium examinations to exclude perforation., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: The use of medical compression stockings (MCS) in patients with peripheral arterial disease (PAD) and diabetes is the subject of an ongoing critical debate. While reducing leg edema of various origins by improving venous back flow, there is a concern about additional arterial flow obstruction when compression therapy is applied in pre-existing PAD. The aim of this study is to obtain further information on the use of class I MCS in patients with advanced PAD and to evaluate the framework conditions for a safe application., Methods: The total collective (n = 55) of this prospective, clinical cohort study consisted of 24 patients with PAD Fontaine stage IIb and higher studied before revascularization, of whom 16 patients were examined again after revascularization, and 15 healthy participants included for reference. The microperfusion of the lower extremity of all participants was examined in a supine, elevated, and sitting position using the oxygen to see (O2C) method., Results: The results indicate that leg positioning had the strongest influence on microcirculation (SO2 and flow: p = 0.0001), whereas MCS had no significant effect on the perfusion parameters (SO2: p = 0.9936; flow: p = 0.4967) and did not lead to a deterioration of values into critical ranges., Conclusion: Mild medical compression therapy appears to be feasible even in patients with advanced PAD. Larger studies are warranted to observe any long-term effects, in particular for the treatment of reperfusion edema after revascularization., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background: Optimal pain management is one of the core elements of Enhanced Recovery After Surgery (ERAS®) protocols and remains a challenge. Acupuncture (AC) is an effective treatment for various pain conditions. Systematic and personalized allocation of acupoints may be decisive for efficacy., Methods: Based on the predominant pressure sensitivity of six gastrointestinal (GI) checkpoints (G1-G6), we devised a method to detect personalized patterns of pain and a corresponding set of acupoints. We performed a single AC treatment with semi-permanent needles and assessed the visual analogue scale (VAS) score, pain threshold based on pressure algometry (PA), and temperature changes on abdominal skin areas before and 5 min after AC., Results: Between April and June 2021, thirty-eight patients were prospectively included in this pilot study. The mean reduction in subjective pain sensation as assessed by VAS was 86%, paralleled by an augmentation of the pain threshold as measured by PA by 64%. A small but significant increase in the skin temperature was observed above the abdominal surface. These effects were independent of the type of surgery., Conclusion: Checkpoint acupuncture may be a complementary tool for postoperative pain management. Further investigations are needed to explore this analgesic effect., (© 2023. The Author(s).)

Introduction: The aim of this study was to determine the extent to which regular monitoring of maternal free thyroxine level and pregnancy-adapted L-thyroxine replacement therapy before and during pregnancy in patients with existing or newly diagnosed latent and manifest hypothyroidism as well as hypothyroxinemia can influence the rate of premature births., Materials and Methods: This is a retrospective cohort study assessing 1440 pseudonymized survey questionnaires to evaluate the risks of premature birth with two study groups from the same medical practice, and a nationally recruited control group. Study group A (n = 360) had already been taking L-thyroxine prior to conception, study group B (n = 580) started taking it after conception. Both study groups had a maximum gestational age of 12 + 0 GW. In the study groups, TSH and free thyroxine levels were determined regularly for dose adjustment purposes. The aim was to keep the free thyroxine level in the euthyroid hyperthyroxinemic range within the pregnancy adapted reference range. The control group (n = 500) had taken L-thyroxine during pregnancy according to criteria that were not known, as the questionnaire did not include any questions regarding this matter. Taking other risk factors into account, the influence of pregnancy-adapted L-thyroxine replacement therapy on the rate of premature births was determined using logistic regression analysis., Results: Compared with the control group, the premature birth rate was 70% lower (p < 0.0001) in study group A and 42% lower in study group B (p = 0.0086), while the odds ratio, at 3.46, was particularly significant in study group A. High blood pressure (odds ratio 5.21), body mass index per kg/m 2 (odds ratio 0.91) and S. p. premature birth were identified as other independent risk factors., Conclusion: The results show an association between more intensive thyroid diagnostics and pregnancy-adapted L-thyroxine replacement therapy and a decrease in premature births. Further studies should be conducted to confirm these results., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: Botulinum toxin injections in the anal sphincter apparatus (Botox) and enteral neuromodulation (ENM) are options for treatment of refractory chronic constipation. We present a retrospective comparative observational study., Patients and Methods: From 2014 to 2022, pediatric patients with chronic constipation were either treated with Botox or ENM with continuation of conservative treatment. Comparison was conducted regarding the primary outcome variables defecation frequency, stool consistency, and abdominal pain. Secondary outcomes were fecal incontinence, enuresis, change of medication and safety of treatment., Results: 19 Botox patients (10 boys, 9 girls, 12 patients with Hirschsprung disease (HD), 7 patients with functional constipation (FC)) were compared to 24 ENM patients (18 boys, 6 girls, 12 HD patients, 7 FC patients). Groups differed significantly in age (5.0 years (Botulinum toxin) and 6.5 years (ENM), mean values, p-value 0.008). Improvement of constipation was seen in 68% (n = 13/19) of Botox and 88% (n = 21/24) of ENM patients (p = 0.153). Influence of etiology on therapeutic effects was not observed. Complications were minor., Conclusions: Botox and ENM can be considered as valuable and effective treatment options in refractory chronic constipation. Prospective, large-population studies should be designed to enable improved evidence., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background/aim: The aim of this study was to evaluate patient preferences regarding cervical dysplasia clinics. Specifically, preferences in terms of diagnostic and therapeutic pathways as well as logistical and structural aspects were addressed to recognize unmet needs and improve existing structures of cervical dysplasia care., Patients and Methods: This questionnaire-based study was conducted between June and December 2022 at an academic medical center in Southwestern Germany. A total of 226 patients who had an appointment at the certified dysplasia clinic were included., Results: The vast majority of patients (74.8%) preferred counseling at the certified dysplasia clinic in the case of an abnormal finding of the cervix or labia. A prompt appointment (within a maximum of 4 weeks), a timely notification about test results (within a maximum of 2 weeks), a travel time <60 minutes and seeing the same doctor during follow-up appointments were recognized as important aspects. While about half of the patients (53.5%) were indifferent to the sex of the gynecologist, almost all of the remaining patients stated they would prefer to be seen by a female doctor (44.3% female doctor vs. 2.2% male doctor)., Conclusion: Most women expect very timely appointments and result notifications. Moreover, they favor short travel times and continuity of care. The identified patient preferences should be considered to increase patient satisfaction and quality of care when developing and optimizing management at specialized dysplasia clinics., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Advances in therapy of metastatic castration-refractory prostate cancer (mCRPC) resulted in more therapeutic options and led to a higher need of predictive/prognostic biomarkers. Systemic inflammatory biomarkers could provide the basis for personalized treatment selection. This study aimed to assess the modified Glasgow Prognostic Score (mGPS), the neutrophile-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and the systemic immune-inflammation index (SII) in men with mCRPC under docetaxel., Methods: Patients with mCRPC and taxane chemotherapy at a tertiary care centre between 2010 and 2019 were screened retrospectively. The biomarkers mGPS, NLR, PLR and SII were assessed and analyzed for biochemical/radiologic response and survival., Results: We included 118 patients. Of these, 73 (61.9%) had received docetaxel as first-line, 31 (26.2%) as second-line and 14 (11.9%) as third-line treatment. For biochemical response, mGPS (odds ratio (OR) 0.54, p = 0.04) and PLR (OR 0.63, p = 0.04) were independent predictors in multivariable analysis. SII was significant in first-line cohort only (OR 0.29, p = 0.02). No inflammatory marker was predictive for radiologic response. In multivariable analysis, mGPS and NLR (hazard ratio (HR) 1.71 and 1.12, both p < 0.01) showed significant association with OS in total cohort and mGPS in the first-line cohort (HR 2.23, p < 0.01). Haemoglobin (Hb) and alkaline phosphatase (AP) showed several significant associations regarding 1 year, 3 year, OS and biochemical/radiologic response., Conclusions: Pre-treatment mGPS seems a promising prognostic biomarker. A combination of mGPS, NLR and further routine markers (e.g., Hb and AP) could yield optimized stratification for treatment selection. Further prospective and multicentric assessment is needed., (© 2022. The Author(s).)

Background: It remains challenging in clinical practice to perform optimal pain management following bariatric surgeries. Acupuncture (AC) is an effective method of postoperative pain management, but its clinical efficacy depends on the rationale used to select AC points., Methods: We developed a method to identify individual patterns of pain and a corresponding set of acupoints (corrAC) based on the relative pressure sensitivity of six abdominal visceral pressure points, i.e., the gastrointestinal (GI) checkpoints (G1-G6). Patients with moderate to severe pain were included and received a single AC treatment following surgery. The visual analog scale (VAS) score, pain threshold, and skin temperature were assessed before AC and at 5 min, 1 h, and 24 h following AC. AC was performed with 1-mm-deep permanent needles., Results: From April 2021 to March 2022, 72 patients were included in the analysis. Fifty-nine patients received corrAC, whereas 13 received a noncorresponding AC (nonAC) as an internal control. Patients receiving corrAC showed a significant reduction (74%) in pain at 5 min after treatment (p < 0.0001) and a significant increase (37%) in the pain threshold (p < 0.0001). In this group, a significant increase in skin temperature above G1, G3, G4, and G5 was observed. Patients receiving nonAC showed neither significant pain reduction nor significant changes in pain threshold. The skin above G3 and G4 did not reveal temperature changes., Conclusion: Checkpoint AC may be an effective tool in postoperative pain therapy after bariatric surgery. Vegetative functional involvement might be associated with pain relief., (© 2023. The Author(s).)

The primary aim of this study was to assess the incidence of a difficult airway and emergency tracheostomy in patients with orofacial infections originating in the mandible, and a secondary aim was to determine the potential predictors of difficult intubation. This retrospective single-center study included all patients who were referred between 2015 and 2022 with an orofacial infection originating in the mandible and who were surgically drained under intubation anesthesia. The incidence of a difficult airway regarding ventilation, laryngoscopy, and intubation was analyzed descriptively. Associations between potential influencing factors and difficult intubation were examined via multivariable analysis. A total of 361 patients (mean age: 47.7 years) were included in the analysis. A difficult airway was present in 121/361 (33.5%) patients. Difficult intubation was most common in patients with infections of the massetericomandibular space (42.6%), followed by infections of the mouth floor (40%) and pterygomandibular space (23.5%). Dyspnea and stridor were not associated with the localization of infection ( p = 0.6486/ p = 0.4418). Multivariable analysis revealed increased age, restricted mouth opening, higher Mallampati scores, and higher Cormack-Lehane classification grades as significant predictors of difficult intubation. Higher BMI, dysphagia, dyspnea, stridor and a non-palpable mandibular rim did not influence the airway management. Patients with a difficult airway were more likely to be admitted to the ICU after surgery than patients with regular airway were ( p = 0.0001). To conclude, the incidence of a difficult airway was high in patients with orofacial infections originating in the mandible. Older age, limited mouth opening, a higher Mallampati score, and a higher Cormack-Lehane grade were reliable predictors of difficult intubation.

Introduction: Functional status is one of the most important issues of geriatric care. Polypharmacy seems to be a modifiable factor associated with functional decline in older adults. However, the impact of pharmacotherapy optimization on the activities of daily living in patients undergoing geriatric rehabilitation has not been investigated prospectively so far., Methods: This post hoc analysis of a subsample of the VALFORTA study included individuals only undergoing geriatric rehabilitation with a length of in-hospital stay of at least 14 days. Medication was modified according to the FORTA rules in the intervention group while in the control group standard drug treatment was applied. Both groups received comprehensive geriatric treatment., Results: The intervention and control groups consisted of 96 and 93 individuals respectively. They did not differ according to basic data except for age and Charlson Comorbidity Index (CCI) on admission. On discharge, activities of daily living (Barthel index, BI) were improved in both groups. An increase of at least 20 points of the BI was observed in 40% of patients in the intervention group and in 12% of patients in the control group (p< 0.001). Logistic regression analysis with an increase of at least 20 BI-points was significantly and independently associated with patient group (2.358, p< 0.02), BI on admission (0.957, p< 0.001), and the CCI (0.793, p< 0.041)., Conclusion: This post hoc analysis of a subsample of older individuals hospitalized for geriatric rehabilitation demonstrates a significant additional improvement in activities of daily living by modification of medication according to FORTA., Registration: DRKS-ID: DRKS00000531., (© 2023. The Author(s).)

Purpose: The primary aim was to determine the incidence of intracranial hemorrhage (ICH) after mild traumatic brain injury (mTBI) in patients aged ≥ 65 years. The secondary aim was to identify risk factors for intracranial lesions and evaluate the need for in-hospital observation in this age group., Methods: This observational retrospective single-center study included all patients aged ≥ 65 years who were referred to our clinic for oral and plastic maxillofacial surgery following mTBI over a five-year period. Demographic and anamnesis data, clinical and radiological findings, and treatment were analyzed. Acute and delayed ICH and patient outcomes during hospitalization were evaluated using descriptive statistical analysis. A multivariable analysis was performed to find associations between CT findings and clinical data., Results: A total of 1,062 patients (55.7% male, 44.2% female) with a mean age of 86.3 years were included in the analysis. Ground-level fall was the most frequent cause of trauma (52.3%). Fifty-nine patients (5.5%) developed an acute traumatic ICH, and 73 intracerebral lesions were radiologically observed. No association was detected between ICH rate and antithrombotic medication (p = 0.4353). The delayed ICH rate was 0.09% and the mortality rate was 0.09%. Significant risk factors for increased ICH were a Glasgow Coma Scale score of < 15, loss of consciousness, amnesia, cephalgia, somnolence, dizziness, and nausea according to multivariable analysis., Conclusion: Our study showed a low prevalence of acute and delayed ICH in older adults with mTBI. The ICH risk factors identified here should be considered when revising guidelines and developing a valid screening tool. Repeat CT imaging is recommended in patients with secondary neurological deterioration. In-hospital observation should be based on an assessment of frailty and comorbidities and not on CT findings alone., (© 2023. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

The aim of the study was to determine the factors influencing the development of recurrence after the surgical treatment of odontogenic maxillary sinusitis in an oral and maxillofacial surgery clinic over a 7-year period. Demographic and anamnesis data, clinical and radiological findings, treatment and outcome were analyzed. A multivariable analysis was performed to find associations between patient age, causative focus, surgical access for sinus revision, multilayer closure with a buccal fat pad, inferior meatal antrostomy (IMA) for temporary sinus drainage and sinusitis recurrence. A total of 164 patients with a mean age of 51.7 years were included. Sinusitis recurrence was observed in nine patients (5.48%) within 6 months after primary surgery. No significant correlation was detected between patient age, causative focus, surgical access for sinus revision, multilayer closure with a buccal fat pad, IMA for sinus drainage and the development of recurrence ( p > 0.05). Patients with a history of antiresorptive-related osteonecrosis of the jaw showed a significant tendency toward disease recurrence ( p = 0.0375). In conclusion, except for antiresorptive administration, none of the investigated variables were related to a higher risk of sinusitis recurrence. We encourage a combined approach of intraoral removal of the infective focus and sinus drainage via FESS, as well as an individual treatment decision in a multidisciplinary setting with collaboration between dentistry, maxillofacial surgery and otorhinolaryngology to avoid sinusitis recurrence.

Background: In Head and neck cancer (HNC) angiogenesis is essential for tumor progression and metastasis. Small extracellular vesicles (sEVs) from HNC cell lines alter endothelial cell (EC) functions towards a pro-angiogenic phenotype. However, the role of plasma sEVs retrieved from HNC patients in this process is not clear so far., Methods: Plasma sEVs were isolated on size exclusion chromatography columns from 32 HNC patients (early-stage UICC I/II: 8, advanced-stage UICC III/IV: 24), 12 patients with no evident disease after therapy (NED) and 16 healthy donors (HD). Briefly, sEVs were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), BCA protein assays and Western blots. Levels of angiogenesis-associated proteins were determined using antibody arrays. The interaction of fluorescently-labeled sEVs with human umbilical vein ECs was visualized by confocal microscopy. The functional effect of sEVs on tubulogenesis, migration, proliferation and apoptosis of ECs was assessed., Results: The internalization of sEVs by ECs was visualized using confocal microscopy. Based on antibody arrays, all plasma sEVs were enriched in anti-angiogenic proteins. HNC sEVs contained more pro-angiogenic MMP-9 and anti-angiogenic proteins (Serpin F1) than HD sEVs. Interestingly, a strong inhibition of EC function was observed for sEVs from early-stage HNC, NED and HD. In contrast, sEVs from advanced-stage HNC showed a significantly increased tubulogenesis, migration and proliferation and induced less apoptosis in ECs than sEVs from HD., Conclusions: In general, plasma sEVs carry a predominantly anti-angiogenic protein cargo and suppress the angiogenic properties of ECs, while sEVs from (advanced-stage) HNC patients induce angiogenesis compared to HD sEVs. Thus, tumor-derived sEVs within the plasma of HNC patients might shift the angiogenic switch towards angiogenesis., (© 2023. The Author(s).)

The primary aim was to evaluate the compliance of cranial CT indication with the national guideline-based decision rules in patients after mTBI. The secondary aim was to determine the incidence of CT pathologies among justified and unjustified CT scans and to investigate the diagnostic value of these decision rules. This is a retrospective, single-center study on 1837 patients (mean age = 70.7 years) referred to a clinic of oral and maxillofacial surgery following mTBI over a five-year period. The current national clinical decision rules and recommendations for mTBI were retrospectively applied to calculate the incidence of unjustified CT imaging. The intracranial pathologies among the justified and unjustified CT scans were presented using descriptive statistical analysis. The performance of the decision rules was ascertained by calculating the sensitivity, specificity, and predictive values. A total of 123 intracerebral lesions were radiologically detected in 102 (5.5%) of the study patients. Most (62.1%) of the CT scans strictly complied with the guideline recommendations, and 37.8% were not justified and likely avoidable. A significantly higher incidence of intracranial pathology was observed in patients with justified CT scans compared with patients with unjustified CT scans (7.9% vs. 2.5%, p < 0.0001). Patients with loss of consciousness, amnesia, seizures, cephalgia, somnolence, dizziness, nausea, and clinical signs of cranial fractures presented pathologic CT findings more frequently ( p < 0.05). The decision rules identified CT pathologies with 92.28% sensitivity and 39.08% specificity. To conclude, compliance with the national decision rules for mTBI was low, and more than a third of the CT scans performed were identified as "likely avoidable". A higher incidence of pathologic CT findings was detected in patients with justified cranial CT imaging. The investigated decision rules showed a high sensitivity but low specificity for predicting CT pathologies.

The primary aim was to determine the clinical indicators for primary cranial CT imaging in patients after mild traumatic brain injury (mTBI). The secondary aim was to evaluate the need for post-traumatic short-term hospitalization based on primary clinical and CT findings. This was an observational retrospective single-centre study of all the patients who were admitted with mTBI over a five-year period. Demographic and anamnesis data, the clinical and radiological findings, and the outcome were analyzed. An initial cranial CT (CT0) was performed at admission. Repeat CT scans (CT1) were performed after positive CT0 findings and in cases with in-hospital secondary neurological deterioration. Intracranial hemorrhage (ICH) and the patient's outcome were evaluated using descriptive statistical analysis. A multivariable analysis was performed to find associations between the clinical variables and the pathologic CT findings. A total of 1837 patients (mean age: 70.7 years) with mTBI were included. Acute ICH was detected in 102 patients (5.5%), with a total of 123 intracerebral lesions. In total, 707 (38.4%) patients were admitted for 48 h for in-hospital observation and six patients underwent an immediate neurosurgical intervention. The prevalence of delayed ICH was 0.05%. A Glasgow Coma Scale (GCS) of <15, loss of consciousness, amnesia, seizures, cephalgia, somnolence, dizziness, nausea, and clinical signs of fracture were identified as clinical factors with significantly higher risk of acute ICH. None of the 110 CT1 presented clinical relevance. A GCS of <15, loss of consciousness, amnesia, seizures, cephalgia, somnolence, dizziness, nausea, and clinical signs of cranial fractures should be considered absolute indicators for primary cranial CT imaging. The reported incidence of immediate and delayed traumatic ICH was very low and hospitalization should be decided individually considering both the clinical and CT findings.

Background: Depres sion is reported in up to 90% of cancer patients but to this date, a standardized screening tool for depression specifically modified for patients diagnosed with brain tumors is lacking. Thus, this study aims to develop an adapted screening tool and identify a suitable time slot for screening., Methods: Sixty-one patients with brain lesions were interviewed prior to neurosurgical resection. For screening purposes, established depression scores were used. A study-specific questionnaire (SSQ) was developed based on patient interviews prior to the trial. Two subgroups were analyzed: patients with benign and patients with malignant tumors (including brain metastases). As a subgroup within malignant lesions, patients with glioblastoma (GBM) were also analyzed separately., Results: Of patients, 87.5% with GBM presented with results > 16 points on the Center for Epidemiologic Studies Depression Scale (CES-D) after surgery. A decline in patients with benign brain tumors (p = 0.0058) and an increase in patients with malignant tumors (p = 0.0491) could be shown over time for CES-D scores. In this study, we established a new prototype screening tool for depression. In patients diagnosed with GBM, the number of patients needed to screen for identification of symptoms of depression was 1.59. Best time for screening was 35 days after surgery., Conclusions: Considering the high prevalence and low number needed to screen of depression in patients diagnosed with GBM, we strongly encourage their routine screening during follow-up appointments (35 days after surgery). We encourage a plan to further establish the questionnaire developed in this pilot study., (© 2023. The Author(s).)

Background: Diabetes mellitus (DM) is one of the most frequent comorbidities in patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a higher rate of severe course of coronavirus disease (COVID-19). However, data about post-COVID-19 syndrome (PCS) in patients with DM are limited., Methods: This multicenter, propensity score-matched study compared long-term follow-up data about cardiovascular, neuropsychiatric, respiratory, gastrointestinal, and other symptoms in 8,719 patients with DM to those without DM. The 1:1 propensity score matching (PSM) according to age and sex resulted in 1,548 matched pairs., Results: Diabetics and nondiabetics had a mean age of 72.6 ± 12.7 years old. At follow-up, cardiovascular symptoms such as dyspnea and increased resting heart rate occurred less in patients with DM (13.2% vs. 16.4%; p = 0.01) than those without DM (2.8% vs. 5.6%; p = 0.05), respectively. The incidence of newly diagnosed arterial hypertension was slightly lower in DM patients as compared to non-DM patients (0.5% vs. 1.6%; p = 0.18). Abnormal spirometry was observed more in patients with DM than those without DM (18.8% vs. 13; p = 0.24). Paranoia was diagnosed more frequently in patients with DM than in non-DM patients at follow-up time (4% vs. 1.2%; p = 0.009). The incidence of newly diagnosed renal insufficiency was higher in patients suffering from DM as compared to patients without DM (4.8% vs. 2.6%; p = 0.09). The rate of readmission was comparable in patients with and without DM (19.7% vs. 18.3%; p = 0.61). The reinfection rate with COVID-19 was comparable in both groups (2.9% in diabetics vs. 2.3% in nondiabetics; p = 0.55). Long-term mortality was higher in DM patients than in non-DM patients (33.9% vs. 29.1%; p = 0.005)., Conclusions: The mortality rate was higher in patients with DM type II as compared to those without DM. Readmission and reinfection rates with COVID-19 were comparable in both groups. The incidence of cardiovascular symptoms was higher in patients without DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abumayyaleh, Núñez Gil, Viana-LLamas, Raposeiras Roubin, Romero, Alfonso-Rodríguez, Uribarri, Feltes, Becerra-Muñoz, Santoro, Pepe, Castro Mejía, Signes-Costa, Gonzalez, Marín, López-País, Manzone, Vazquez Cancela, Paeres, Masjuan, Velicki, Weiß, Chipayo, Fernandez-Ortiz, El-Battrawy, Akin, HOPE COVID-19 investigators.)

The achievement of major molecular response (MMR, BCR::ABL1 ≤ 0.1% IS) within the first year of treatment with tyrosine kinase inhibitors (TKI) is a milestone in the therapeutic management of patients with newly diagnosed chronic myeloid leukemia (CML). We analyzed the predictive value of gene expression levels of ESPL1 /Separase, PTTG1 /Securin and PTTG1IP /Securin interacting protein for MMR achievement within 12 months. Relative expression levels (normalized to GUSB ) of ESPL1 , PTTG1 and PTTG1IP in white blood cells of patients (responders n = 46, non-responders n = 51) at the time of diagnosis were comparatively analyzed by qRT-PCR. 3D scatter plot analysis combined with a distance analysis performed with respect to a commonly calculated centroid center resulted in a trend to larger distances for non-responders compared to the responder cohort ( p = 0.0187). Logistic regression and analysis of maximum likelihood estimates revealed a positive correlation of distance (cut-off) with non-achieving MMR within 12 months ( p = 0.0388, odds ratio 1.479, 95%CI: 1.020 to 2.143). Thus, 10% of the tested non-responders (cut-off ≥ 5.9) could have been predicted already at the time of diagnosis. Future scoring of ESPL1 , PTTG1 and PTTG1IP transcript levels may be a helpful tool in risk stratification of CML patients before initiation of TKI first = line treatment.

Background: The aging of our societies leads to a higher prevalence of multimorbidity and therefore polypharmacy, which often results in inappropriate drug treatment. To address this issue, numerous listing approaches, such as the Fit fOR The Aged (FORTA) list have been developed. FORTA's positive impact on the quality of medications and relevant clinical outcomes has been shown. Based on new emerging evidence and experiences with the existing FORTA lists, we aimed to update the FORTA lists in several European countries/regions., Methods: Two-step Delphi consensus procedures were conducted in Poland, UK/Ireland, Italy, Spain, the Nordic countries, The Netherlands and France. The existing European FORTA lists served as survey proposals., Results: Thirty-two experts agreed to take part in this study (return rate: 96.9%). The country/region-specific overall consensus for all items and participants after the first round was > 90%. FORTA lists from six participating countries, plus the FORTA list for the German-speaking countries, were collated into the new EURO-FORTA List, which now contains 267 items aligned to 27 indications. Three items were added to the EURO-FORTA List, and no drugs were deleted. Eight FORTA items were relabeled, and 96.9% of the labels remained unchanged., Conclusion: In this study, seven new country/region specific FORTA lists, as well as a new overarching EURO-FORTA List, were developed. An overall increase in the mean consensus coefficient and increases for all disease-specific mean consensus coefficients show a wider consensus among participants. The new lists have the potential to improve drug therapy in older people internationally., (© 2023. The Author(s).)

Background/aim: This retrospective cohort study enrolled hospitalized women with 24+0 to 33+6 gestational weeks with conditions associated with preterm birth. We evaluated the ability of vaginal swab isolates to guide antibiotic management decisions in the setting of threatened preterm towards a clinical advantage, i.e., longer delay between diagnosis and birth, better neonatal outcomes., Patients and Methods: Vaginal swabs were obtained from all patients and antibiotic resistance profiles determined in case of growth. The cohort was divided into two groups: the antibiogram-noncongruently managed Group 1 and the antibiogram-congruently managed Group 2. These groups were compared in regard to multiple maternal and neonatal endpoints., Results: In total, 698 cases were analyzed - 224 in Group 1 and 474 in Group 2. Antibiotics were ordered/continued by the treating physician in 138 cases (138/698; 19.8%) upon review of vaginal swab cultures results. Forty-five among them (32.6%) received antibiotics inactive against the isolated bacteria. 335 (25.4%) patients had only normal vaginal flora, and 95.6% of them had not received antibiotics. Facultatively pathogenic microorganisms were isolated in 52% patients. Only 5% of the neonates had bacterial isolates identical to those of their mothers. There were no significant differences in outcomes between Group 1 and Group 2., Conclusion: No association was found between a swab-result-guided antibiotic management protocol and maternal or fetal outcome in the setting of preterm birth risk between 24 and 34 gestational weeks. These findings underline the importance of critical rethinking the frequency of vaginal smears and fine-tuning the indications for antibiotic treatment., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)