Pronounced neonatal breast enlargement beyond the first week of life and its regression correlates with serum prolactin levels - a case series.

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.

Influence of adjuvant therapies on organ-specific recurrence of cutaneous melanoma: A multicenter study on 1383 patients of the prospective DeCOG registry ADOReg.

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.

The Effect of Revascularization on Lower Limb Circulation Parameters in Symptomatic Peripheral Arterial Disease.

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 (SO2), 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, SO2 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 SO2, rHb, and the ABI did not. Conclusions: Elevated leg SO2 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.

Validation of MyFORTA: An Automated Tool to Improve Medications in Older People Based on the FORTA List.

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.

Acute and Long-Term Toxicity after Planned Intraoperative Boost and Whole Breast Irradiation in High-Risk Patients with Breast Cancer-Results from the Targeted Intraoperative Radiotherapy Boost Quality Registry (TARGIT BQR).

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.

Study protocol for a non-inferiority, multicenter, randomized study to evaluate a smartphone app-based follow-up program after bariatric surgery (BELLA plus trial).

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.

Effect of severity and etiology of chronic kidney disease in patients with heart failure with mildly reduced ejection fraction.

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.

Evaluation of Different Patterns of Zygomaticoorbital Complex Fractures.

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.

Increase of Cardiac Autoantibodies Against Beta-2-adrenergic Receptor During Acute Cellular Heart Transplant Rejection.

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 (ß-2AR: EAINCYANETCCDFFTNQAY) to be upregulated in ACR-HTx (intensities: 0.80 versus 1.31, P = 0.0413). Likewise, patients positive for ß-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.

Motivational Interviewing improves postoperative nutrition goals within the Enhanced Recovery after Surgery (ERAS®) pathway in elective bowel surgery - A randomized clinical pilot trial.

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.

Influence of motivational interviewing on postoperative mobilization in the enhanced recovery after surgery (ERAS®) pathway in elective colorectal surgery - a randomized patient-blinded pilot study.

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".

Effect of anaemia and iron deficiency in heart failure with mildly reduced ejection fraction.

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.

Sacral neuromodulation for constipation and fecal incontinence in children and adolescents - study protocol of a prospective, randomized trial on the application of invasive vs. non-invasive technique.

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).

Effect of Heart Failure Pharmacotherapies in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

OBJECTIVE: The study sought to comprehensively investigate the effect of heart failure (HF) pharmacotherapies in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BACKGROUND: In the absence of randomized controlled trials, guideline recommendations concerning HF-related therapies in patients with HFmrEF are limited. METHODS: 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 transport protein 2 inhibitors (SGLT2i) was investigated for all-cause mortality at 30 months (median follow-up) and HF-related rehospitalization. RESULTS: 2,109 patients with HFmrEF were included. Treatment with BB (27.0% vs. 35%; HR = 0.737; 95% 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 lower risk of 30-months 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: BB, ACEi/ARB/ARNI and SGLT2i were independently associated with 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.

Although heart failure with mildly reduced ejection fraction (HFmrEF) affects one out of four patients with heart failure (HF), limited evidence regarding HF pharmacotherapies for the treatment of patients with HFmrEF is available. The present study investigates the 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 transport protein 2 inhibitors (SGLT2i) on long-term outcomes using a large registry-based dataset of 2,109 patients hospitalized with HFmrEF. Treatment with BB, ACEi/ARB/ARNI and SGLT2i was independently associated with a lower risk of long-term all-cause mortality, even after multivariable adjustment and propensity score matching, specifically when applied in combination. In contrast, MRA treatment was not associated with outcomes in the present study. The present study supports the evidence that patients with HFmrEF may benefit from HF pharmacotherapies similar than patients with HF with reduced ejection fraction (HFrEF).

Differences in neonatal gastric tubes during insertion into a 3D model in relation to risk of potential perforation.

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.

Perinatal Outcome in Pregnant Women With Isolated Oligohydramnios Diagnosed With the Single Deepest Pocket Method.

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.

Algorithm for Rapid Exclusion of Clinically Relevant Plasma Levels of Direct Oral Anticoagulants in Patients Using the DOAC Dipstick: An Expert Consensus Paper.

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.

Fetal MRI-Based Mediastinal Shift Angle (MSA) and Percentage Area of Left Ventricle (pALV) as Prognostic Parameters for Congenital Diaphragmatic Hernia.

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.

Nuclear pore protein POM121 regulates subcellular localization and transcriptional activity of PPARγ.

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.

The Subdiaphragmatic Angle Of The Gastric Tube In Neonates - A Potential Predictor For Perforations?

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.