Pleural Effusion and Chylothorax in Congenital Diaphragmatic Hernia-Risk Factors, Management and Outcome.

Background: Pleural effusion and chylothorax are common complications in the treatment of congenital diaphragmatic hernia (CDH). We set out to identify risk factors for chylothorax development in patients with CDH and to investigate the association of pleural effusion and chylothorax with neonatal morbidity and mortality. Methods: In this retrospective cohort study, we included 396 neonates with CDH treated at our institution between January 2013 and June 2019. Preoperative and postoperative chest radiographs and clinical data were evaluated and correlated with morbidity, complications and mortality. Results: Laboratory-confirmed chylothorax occurred in 58 (18.6%) of all CDH cases. Pleural effusion was frequently observed as a postoperative complication but also occurred as a pre-existing condition. Neonates with large defects of size C and D, patch repair, the need for presurgical and/or postsurgical ECMO support, pulmonary hypertension, liver-up phenomenon and lower relative fetal lung volume were associated with higher occurrences of chylothorax. After stepwise logistic regression, larger CDH defects (p < 0.0001) and the need for postsurgical ECMO (p = 0.0158) remained significant risk factors for CTX to occur (AUC 0.71). The same potential risk factors were used to assess their association with both presurgical and postsurgical pleural effusion. After stepwise logistic regression, only the need for presurgical ECMO remained significantly associated with presurgical PE (p < 0.01, AUC 0.65) and patch repair as the therapeutic intervention remained significantly associated with the occurrence of postsurgical PE (p < 0.0001, AUC 0.80). Patients with CTX had longer durations of both MV (p < 0.0001) and subsequent ventilatory assistance with spontaneous breathing (p = 0.0004), increased total lengths of hospitalization (p < 0.0001), increased durations of ECMO (p < 0.01) and increased incidences of CLD (p < 0.0001) compared to patients without CTX. No significant difference could be found for survival in both groups (p = 0.12). Conclusions: Our data suggest that the incidence of chylothorax is associated with large diaphragmatic defects, the need for postsurgical ECMO and the development of chronic lung disease, but not with survival.

Comparison of T-POD and SAM Pelvic Sling II and the influence of attachment level in the initial management of unstable pelvic type C injuries - a cadaveric study.

BACKGROUND: Type C pelvic fractures (AO/OTA) are severe injuries that frequently lead to bleeding and hemodynamic instability. Pelvic binders play a crucial role in their initial management. Placement at the correct level in the prehospital setting is challenging. The aim of this study was to compare two pelvic binders regarding their effectiveness in reducing intrapelvic volume and increasing intrapelvic pressure in patients with type C pelvic fractures (AO/OTA) when applied at three different levels. METHODS: Rotationally and vertically unstable pelvic injuries (AO/OTA classification 61-C1.1) were produced in five fresh-frozen human cadaveric specimens. Intrapelvic volume, vesical pressure and compression pressure within the pubic symphysis and the sacroiliac joint were measured when applying a SAM Pelvic Sling II and a T-POD at the level of the greater trochanter as well as levels higher and lower than recommended. RESULTS: Comparison of the two pelvic binders positioned at the recommended level (greater trochanter) showed no significant difference in volume reduction (13.85 ± 31.37 cm3, p = 0.442), however, increase in vesical pressure was significantly higher when using the T-POD (5.80 ± 3.27 cmH2O, p = 0.017). When positioned at the level of the iliac crest, vesical pressure increase and intrapelvic volume reduction were significantly greater with the T-POD (14.00 ± 8.57 cmH2O, p = 0.022 and 10.45 ± 5.45 cm3, p = 0.031 respectively). Application of the SAM Pelvic Sling II below the greater trochanter led to a significantly greater decrease in volume (-32.26 ± 7.52 cm3, p = 0.003) than the T-POD. Comparison of the recommended attachment level with incorrect positioning led to no significant differences for the T-POD, while the SAM Pelvic Sling II achieved a significantly lower volume reduction when placed at the iliac crest (40.15 ± 14.57 cm3, p = 0.012) and a significantly lower increase in vesical pressure when applied below the greater trochanter (3.40 ± 1.52 cmH2O, p = 0.007). CONCLUSION: Direct comparison of the two pelvic binders showed that the T-POD achieved significantly greater results when applied at the recommended level and was less susceptible to incorrect positioning. These outcomes support the preferred use of the T-POD for prehospital emergency pelvic stabilisation.

Malnutrition and vitamin deficiencies after surgery for esophageal and gastric cancer: A metanalysis.

BACKGROUND & AIMS: Patients receiving oncological esophagectomy or gastrectomy are known to be at high risk for vitamin and micronutrient deficiency before, during and after surgery. However, there are no clear guidelines for these cancer patients regarding postoperative vitamin supplementation. METHODS: We conducted a metanalysis consisting of 10 studies regarding vitamin and micronutrient deficiencies after oncological gastric or esophageal resection. 5 databases were searched. RESULTS: Data was sufficient regarding Vitamins B12 and 25-OH D3 as well as calcium. We were able to show deficiencies in 25-OH Vitamin D3 levels (p < 0.001) and lower levels of Vitamin B12 and calcium (bit p < 0.001) when compared to the healthy population. CONCLUSIONS: Patients from these groups are at risk for vitamin deficiencies. A guideline on postoperative supplementation is needed.

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.

Case fatality and functional outcome after spontaneous subarachnoid haemorrhage: A systematic review and meta-analysis of time trends and regional variations in population-based studies.

INTRODUCTION: A previous systematic review of population-based studies from 1973 to 2002 found a decrease in case fatality for spontaneous subarachnoid haemorrhage, but could not find a sufficient number of studies to assess changes in functional outcome. Since then, treatment has advanced distinctly. We assessed whether case fatality has decreased further and whether functional outcome has improved. PATIENTS AND METHODS: We searched PubMed and Web of Science for new population-based studies using the same criteria as in our previous systematic review. We assessed changes in case fatality and functional outcome over time using linear regression. RESULTS: We included 24 new studies with 827 patients and analysed 9542 patients described in 62 study periods between 1973 and 2017. Case fatality decreased by 0.3% (95% CI: -0.7 to 0.1) per year. In a sensitivity analysis excluding studies that did not provide 1-month outcome and outliers, the age and sex-adjusted decrease was 0.1% per year (95% CI: -0.9 to 0.6). The mean case fatality rate decreased from 47% (95% CI: 31-63) in the 1970s to 35% (95% CI: 30-39) in the 1990s, and remained stable in the 2000s (34%; 95% CI: 27-41) and 2010s (38%; 95% CI: 15-60). In 15 studies, the mean proportion of patients living independently increased by 0.2% per year (95%CI: -0.7 to 1.1) and the mean was 45% (95% CI: 39-50) in six studies that reported outcome after 12 months. DISCUSSION AND CONCLUSION: From 1973 to 2017, the case-fatality rate of spontaneous subarachnoid haemorrhage declined overall by 13.5%, but remained stable over the last two decades. The data on time trends in functional outcome were inconclusive.

Oncological right hemicolectomy in a trimodal comparison: open surgery versus laparoscopic procedures with extra- and intracorporeal anastomosis technique.

PURPOSE: This study aimed to investigate the surgical short- and mid-term outcomes, as well as the impact on quality of life and recovery, following oncological right hemicolectomy. To accomplish this, three patient cohorts were examined, which included laparotomy OA), laparoscopy with intracorporeal anastomosis (LIA), and laparoscopy with extracorporeal anastomosis (LEA). Our hypothesis was that the group undergoing intracorporeal anastomosis would demonstrate superior outcomes compared to the other cohorts. METHODS: The analysis included a total of 135 patients who were enrolled between 2015 and 2020. In addition to retrospectively collected data, we conducted follow-up surveys using a validated Gastrointestinal Quality of Life Index (GIQLI) questionnaire and semi-structured interviews. These surveys were conducted between July and September 2021 to gather comprehensive information regarding the patients' quality of life. RESULTS: The study cohort was divided into OA (n = 67), LEA (n = 14), and LIA (n = 54). The duration of surgery was significantly longer in the laparoscopic groups (median = 200.5 (LEA) and 184.0 (LIA) min vs 170.0 min (OA); p = 0.007), while the length of hospital stay was significantly shorter (median = 6.0 and 7.0 days vs 9.0 days; p = 0.005). The overall postoperative complication rate was significantly higher in the laparotomy group compared to the intracorporeal group (64.2% vs 35.2%; p = 0.006), with the extracorporeal group having a rate of 42.9%. Reoperation within 30 days occurred exclusively in the open surgery group (n = 9; 13.43%; p = 0.007). The overall response rate to the survey was 75%. Overall, the GIQLI score was comparable among the three groups, and there were no significant differences in the questions related to recovery, regained function, and contentment. CONCLUSION: The laparoscopic approaches demonstrated significantly lower complication rates compared to laparotomy, while no significant differences were observed between the two laparoscopic techniques.

Treatment of agitation in terminally ill patients with intranasal midazolam versus subcutaneous midazolam: study protocol for a randomised controlled open-label monocentric trial (MinTU Study).

BACKGROUND: Intranasal (i.n.) drug application is a widely known and low-invasive route of administration that may be able to achieve rapid symptom control in terminally ill patients. According to the German S3 guideline "Palliative care for patients with incurable cancer", benzodiazepines, such as midazolam, are recommended for the treatment of terminal agitation. To the best of our knowledge there is no evidence for i.n. midazolam in terminally ill patients. We aim to assess the use of i.n. midazolam as an alternative to subcutaneous administration of the drug. METHODS: In this monocentric, randomised, controlled, open-label investigator initiated trial, n = 60 patients treated at the palliative care unit of a University Hospital will be treated with 5 mg midazolam i.n. versus 5 mg subcutaneous (s.c.) midazolam in the control arm when terminal agitation occurs (randomly assigned 1:1). The estimated recruitment period is 18 months. Treatment efficacy is defined as an improvement on the Richmond Agitation Sedation Scale (Palliative Version) (RASS-PAL) and a study specific numeric rating scale (NRS) before and after drug administration. Furthermore, plasma concentration determinations of midazolam will be conducted at t1 = 0 min, t2 = 5 min, and t3 = 20 min using liquid chromatography/mass spectrometry (LC-MS). The primary objective is to demonstrate non-inferiority of midazolam i.n. in comparison to midazolam s.c. for the treatment of agitation in terminally ill patients. DISCUSSION: Midazolam i.n. is expected to achieve at least equivalent reduction of terminal agitation compared to s.c. administration. In addition, plasma concentrations of midazolam i.n. are not expected to be lower than those of midazolam s.c. and the dynamics of the plasma concentration with an earlier increase could be beneficial. TRIAL REGISTRATION: German Clinical Trials Registry DRKS00026775, registered 07.07.2022, Eudra CT No.: 2021-004789-36.

The Efficacy of the Manual Circumlaryngeal Therapy for Muscle Tension Dysphonia: A Systematic Review and Meta-analysis.

OBJECTIVE: Muscle tension dysphonia (MTD) is the most common functional voice disorder. Behavioral voice therapy is the front-line treatment for MTD, and laryngeal manual therapy may be a part of this treatment. The objective of this study was to investigate the effect of manual circumlaryngeal therapy (MCT) on acoustic markers of voice quality (jitter, shimmer, and harmonics-to-noise ratio) and vocal function (fundamental frequency) through a systematic review with meta-analysis. DATA SOURCES: Four databases were searched from inception to December 2022, and a manual search was performed. REVIEW METHODS: The PRISMA extension statement for reporting systematic reviews incorporating a meta-analysis of health care interventions was applied, and a random effects model was used for the meta-analyses. RESULTS: We identified 6 eligible studies from 30 studies (without duplicates). The MCT approach was highly effective on acoustics with large effect sizes (Cohen's d > 0.8). Significant improvements were obtained in jitter in percent (mean difference of -.58; 95% CI -1.00 to 0.16), shimmer in percent (mean difference of -5.66; 95% CI -8.16 to 3.17), and harmonics-to-noise ratio in dB (mean difference of 4.65; 95% CI 1.90-7.41), with the latter two measurements continuing to be significantly improved by MCT when measurement variability is considered. CONCLUSION: The efficacy of MCT for MTD was confirmed in most clinical studies by assessing jitter, shimmer, and harmonics-to-noise ratio related to voice quality. The effects of MCT on the fundamental frequency changes could not be verified. Further contributions of high-quality randomized control trials are needed to support evidence-based practice in laryngology. Laryngoscope, 134:18-26, 2024.

Development and Validation of a Model for Postpancreatectomy Hemorrhage Risk.

Importance: Postpancreatectomy hemorrhage (PPH) due to postoperative pancreatic fistula (POPF) is a life-threatening complication after pancreatoduodenectomy. However, there is no prediction tool for early identification of patients at high risk of late PPH. Objective: To develop and validate a prediction model for PPH. Design, Setting, and Participants: This retrospective prognostic study included consecutive patients with clinically relevant POPF who underwent pancreatoduodenectomy from January 1, 2009, to May 20, 2023, at the University Hospital Mannheim (derivation cohort), and from January 1, 2012, to May 31, 2022, at the University Hospital Dresden (validation cohort). Data analysis was performed from May 30 to July 29, 2023. Exposure: Clinical and radiologic features of PPH. Main Outcomes and Measures: Accuracy of a predictive risk score of PPH. A multivariate prediction model-the hemorrhage risk score (HRS)-was established in the derivation cohort (n = 139) and validated in the validation cohort (n = 154). Results: A total of 293 patients (187 [64%] men; median age, 69 [IQR, 60-76] years) were included. The HRS comprised 4 variables with associations: sentinel bleeding (odds ratio [OR], 35.10; 95% CI, 5.58-221.00; P < .001), drain fluid culture positive for Candida species (OR, 14.40; 95% CI, 2.24-92.20; P < .001), and radiologic proof of rim enhancement of (OR, 12.00; 95% CI, 2.08-69.50; P = .006) or gas within (OR, 12.10; 95% CI, 2.22-65.50; P = .004) a peripancreatic fluid collection. Two risk categories were identified with patients at low risk (0-1 points) and high risk (≥2 points) to develop PPH. Patients with PPH were predicted accurately in the derivation cohort (C index, 0.97) and validation cohort (C index 0.83). The need for more invasive PPH management (74% vs 34%; P < .001) and severe complications (49% vs 23%; P < .001) were more frequent in high-risk patients compared with low-risk patients. Conclusions and Relevance: In this retrospective prognostic study, a robust prediction model for PPH was developed and validated. This tool may facilitate early identification of patients at high risk for PPH.

[Analysis of the postoperative outcome of 81 cases of nasal reconstruction with direct closure]. / Analyse des postoperativen Verlaufs nach 81 Dehnungsplastiken an der Nase.

BACKGROUND: Direct wound closure (side-to-side closure) for closing nasal defects, is controversially discussed. Yet, data supporting one or the other are lacking. MATERIAL AND METHOD: An explorative, partly retrospective, partly prospective observational study including 81 patients was carried out for assessment of the operative results of after direct wound closure stretching rhinoplasty. The occurrence of complications, the esthetic result and influencing factors were examined. To assess the esthetic result the patient and observer scar assessment scale (POSAS) scores of patients and observers were determined. In both scores seven values were determined (1 point normal skin, 10 points worst imaginable scar). The individual values were added to give a total value (minimum 7-maximum 70). RESULTS: After direct wound closure stretching rhinoplasty, 12 out of 81 patients (15 %) developed complications, in 5 cases suture dehiscence, in 5 cases cyst formation, in 4 cases a wound infection and 2 patients developed cyst formation and a wound infection. All suture dehiscences occurred on the lower third of the nose. Most of the patients were satisfied and assessed the scar with an average total value of 13.4 ± 7.07 (minimum 7, maximum 70, n = 42). In the individual assessments pain (1.14 ± 0.57; minimum 1, maximum 10) was rated best and scar color (2.50 ± 1.76; minimum 1, maximum 10) was rated worst. The total assessment in the observer-POSAS was also good with 12.9 ± 4.8 (minimum 7, maximum 70; n = 32). Elasticity was rated best (1.47 ± 0.88; minimum 1, maximum 7) and scar pigmentation (2.34 ± 1.54; minimum 1, maximum 7) worst. No correlations with a complication were found. CONCLUSION: Direct wound closure stretching rhinoplasty is a safe method, especially for defect coverage in the upper two thirds of the soft tissue covering the nose, which in most cases achieved a good cosmetic result.

Long-term outcomes from upgrade to cardiac resynchronisation therapy in ischaemic versus non-ischaemic heart disease.

BACKGROUND: Cardiac resynchronisation therapy (CRT) can be necessary in patients with chronic heart failure, who have already been provided with transvenous cardiac implantable electrical devices. Upgrade procedures revealed controversial results, while long-term outcomes regarding underlying Ischaemic- (ICM) or Non-Ischaemic heart disease (NICM) have yet to be described. METHODS: The Mannheim Cardiac Resynchronisation Therapy Registry (MARACANA) was designed as a retrospective observational single-centre registry, including all CRT implantations from 2013-2021 (n = 459). CRT upgrades (n = 136) were retrospectively grouped to either ICM (n = 84) or NICM (n = 52) and compared for New York Heart Association classification (NYHA), paced QRS-width, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE) and other heart failure modification aspects in the long-term (59.3 ± 5 months). RESULTS: Baseline-characteristics including paced QRS-width, upgrade indications or NYHA-classification were comparable for both groups (group comparison p>.05). The CRT upgrade improved NYHA (ICM: 2.98 ± 0.4 to 2.29 ± 0.7, NICM: 2.94 ± 0.5 to 2.08 ± 0.5) and the LVEF (ICM: 27.2 ± 6.6 to 38.25 ± 8.8, NICM: 30.2 ± 9.4 to 38.7 ± 13.8%) after five years, irrespective of underlying heart disease (each group p < .05, group comparison p>.05). Only ICM revealed significant improvements in TAPSE (15.9 ± 4.1 to 18.9 ± 4.1 mm) and narrowing of the paced QRS-width (185.4 ± 29 to 147.2 ± 16.3 ms) after five years (each p < .05). CONCLUSIONS: Upgrade to CRT might improve heart failure symptoms and left-ventricular systolic function in the long-term, irrespective of underlying ischaemic or non-ischaemic heart disease.

Cemented versus Cementless Stem Fixation in Revision Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

The number of revision knee arthroplasties (rTKA) is growing significantly as is the use of intramedullary stems for optimized stability. The choice of the most appropriate stem fixation method is still controversial. The purpose of this meta-analysis is to compare cemented versus cementless stem fixation in rTKA. Publications with patients undergoing rTKA with a follow-up > 24 months were systemically reviewed. Extracted parameters included total revision and failure rates for any reason, incidence of aseptic loosening, periprosthetic infection, and radiolucent lines, as well as the clinical outcome. A statistical regression analysis was then performed on all extracted clinical and radiological outcome data. A total of 35 publications met the inclusion criteria and were included and analyzed. Overall, 14/35 publications compared cementless versus cemented stem fixation, whereas 21/35 publications investigated only one stem fixation method. There were no significant differences in revision (p = 0.2613) or failure rates (p = 0.3559) and no differences in the incidence of aseptic loosening (p = 0.3999) or periprosthetic infection (p = 0.1010). The incidence of radiolucent lines was significantly higher in patients with cemented stems (26.2% versus 18.6%, p < 0.0001). However, no differences in clinical outcomes were observed. No superiority of a specific stem fixation method in rTKA was found. Rates of revision or failure for any reason as well as incidence of aseptic loosening and periprosthetic infection in cemented versus cementless stem fixation showed no significant difference. A higher incidence of radiolucent lines was observed in cemented stem fixation; however, no effect was observed on the clinical outcome.

A Multi-Disciplinary MRI Assessment May Optimize the Evaluation of Chondral Lesions in Acute Ankle Fractures: A Prospective Study.

Chondral lesions (CL) in the ankle following acute fractures are frequently overlooked immediately after the injury or diagnosed at a later stage, leading to persistent symptoms despite successful surgery. The literature presents a wide range of discrepancies in the reported incidence of CLs in acute ankle fractures. The objective of this prospective study is to provide a precise assessment of the occurrence of chondral lesions (CLs) in acute ankle fractures through MRI scans conducted immediately after the trauma and prior to scheduled surgery. Furthermore, the study aims to highlight the disparities in the interpretation of these MRI scans, particularly concerning the size and extent of chondral damage, between radiologists and orthopedic surgeons. Over the period of three years, all patients presenting with an unstable ankle fracture that underwent operative treatment were consecutively included in this single-center prospective study. Preoperative MRIs were obtained for all included patients within 10 days of the trauma and were evaluated by a trauma surgeon and a radiologist specialized in musculoskeletal MRI blinded to each other's results. The location of the lesions was documented, as well as their size and ICRS classification. Correlations and kappa coefficients as well as the p-values were calculated. A total of 65 patients were included, with a mean age of 41 years. The evaluation of the orthopedic surgeon showed CLs in 52.3% of patients. CLs occurred mainly on the tibial articular surface (70.6%). Most talar lesions were located laterally (11.2%). The observed CLs were mainly ICRS grade 4. According to the radiologist, 69.2% of the patients presented with CLs. The most common location was the talar dome (48.9%), especially laterally. Most detected CLs were graded ICRS 3a. The correlation between the two observers was weak/fair regarding the detection and classification of CLs and moderate regarding the size of the detected CLs. To enhance the planning of surgical treatment for ankle chondral lesions (CLs), it may be beneficial to conduct an interdisciplinary preoperative assessment of the performed scans. This collaborative approach can optimize the evaluation of ankle CLs and improve overall treatment strategies.

Flow Cytometric Characterization of Hematopoietic Stem and Progenitor Cell Subpopulations in Autologous Peripheral Blood Stem Cell Preparations after Cryopreservation.

Introduction: Autologous stem cell transplantation is a successful routine procedure with only a small number of non-engraftment cases, although the time to hematopoietic recovery may vary considerably across patients. While CD34 has been the decisive marker for enumerating hematopoietic stem and progenitor cells (HSPCs) for more than 30 years, the impact of CD34-positive cellular subpopulations in autologous HSPC grafts on hematopoietic reconstitution remains unclear. Methods: The two-color ISHAGE protocol represents the current gold standard for CD34+ cell enumeration but includes only the number of viable CD45+/CD34+ cells relative to the body weight of the recipient. We adapted a multicolor flow cytometry marker panel for advanced characterization of CD34 subpopulations in retained samples of autologous peripheral blood stem cell products (n = 49), which had been cryostored for a wide range from 4 to 15 years. The flow cytometric analysis included CD10, CD34, CD38, CD45, CD45RA, CD133, and viability staining with 7AAD. The findings were correlated with clinical engraftment data, including reconstitution of leukocytes, neutrophils, and platelets after transplantation (TPL). Results: We demonstrated that the identification of autologous HSPC subpopulations by flow cytometry after cryopreservation is feasible. Regarding the distribution of HSPC subpopulations, a markedly different pattern was observed in comparison to previously published data obtained using fresh autologous material. Our data revealed the largest ratio of lympho-myeloid progenitors (LMPPs) after freezing and thawing, followed by multipotent progenitors and erythroid-myeloid progenitors. A high ratio of LMPPs, representing an immature stage of differentiation, correlated significantly with early neutrophilic granulocyte and leukocyte engraftment (p = 0.025 and p = 0.003). Conversely, a large ratio of differentiated cells correlated with late engraftment of neutrophilic granulocytes (p = 0.024). Overall, successful engraftment was documented for all patients. Conclusion: We established an advanced flow cytometry panel to assess the differentiation ability of cryostored autologous peripheral blood stem cell grafts and correlated it with timely hematopoietic reconstitution. This approach represents a novel and comprehensive way to identify hematopoietic stem and progenitor subpopulations. It is a feasible way to indicate the engraftment capacity of stem cell products.

aCGH Analysis Reveals Novel Mutations Associated with Congenital Diaphragmatic Hernia Plus (CDH+).

Congenital diaphragmatic hernia (CDH) is a major birth anomaly that often occurs with additional non-hernia-related malformations, and is then referred to as CDH+. While the impact of genetic alterations does not play a major role in isolated CDH, patients with CDH+ display mutations that are usually determined via array-based comparative genomic hybridization (aCGH). We analyzed 43 patients with CDH+ between 2012 and 2021 to identify novel specific mutations via aCGH associated with CDH+ and its outcome. Deletions (n = 32) and duplications (n = 29) classified as either pathological or variants of unknown significance (VUS) could be detected. We determined a heterozygous deletion of approximately 3.75 Mb located at 8p23.1 involving several genes including GATA4, NEIL2, SOX7, and MSRA, which was consequently evaluated as pathological. Another heterozygous deletion within the region of 9p23 (9,972,017-10,034,230 kb) encompassing the Protein Tyrosine Phosphatase Receptor Type Delta gene (PTPRD) was identified in 2 patients. This work expands the knowledge of genetic alterations associated with CDH+ and proposes two novel candidate genes discovered via aCGH.

Surface guidance compared with ultrasound-based monitoring and diaphragm position in cone-beam computed tomography during abdominal stereotactic radiotherapy in breath-hold.

Background and purpose: Spirometry induced deep-inspiration-breath-hold (DIBH) reduces intrafractional motion during upper abdominal stereotactic body radiotherapy (SBRT). The aim of this prospective study was to evaluate whether surface scanning (SGRT) is an adequate surrogate for monitoring residual internal motion during DIBH. Residual motion detected by SGRT was compared with experimental 4D-ultrasound (US) and an internal motion detection benchmark (diaphragm-dome-position in kV cone-beam computed tomography (CBCT) projections). Materials and methods: Intrafractional monitoring was performed with SGRT and US in 460 DIBHs of 12 patients. Residual motion detected by all modalities (SGRT (anterior-posterior (AP)), US (AP, craniocaudal (CC)) and CBCT (CC)) was analyzed. Agreement analysis included Wilcoxon signed rank test, Maloney and Rastogi's test, Pearson's correlation coefficient (PCC) and interclass correlation coefficient (ICC). Results: Interquartile range was 0.7 mm (US(AP)), 0.8 mm (US(CC)), 0.9 mm (SGRT) and 0.8 mm (CBCT). SGRT(AP) vs. CBCT(CC) and US(CC) vs. CBCT(CC) showed comparable agreement (PCCs 0.53 and 0.52, ICCs 0.51 and 0.49) with slightly higher precision of CBCT(CC). Most agreement was observed for SGRT(AP) vs. US(AP) with largest PCC (0.61) and ICC (0.60), least agreement for SGRT(AP) vs. US(CC) with smallest PCC (0.44) and ICC (0.42). Conclusions: Residual motion detected during spirometry induced DIBH is small. SGRT alone is no sufficient surrogate for residual internal motion in all patients as some high velocity motion could not be detected. Observed patient-specific residual errors may require individualized PTV-margins.

The Impact of Protective Face Coverings on Acoustic Markers in Voice: A Systematic Review and Meta-Analysis.

BACKGROUND: Wearing respiratory protective masks (RPMs) has become common worldwide, especially in healthcare settings, since the onset of the COVID-19 pandemic. Hypotheses have suggested that sound transmission could be limited by RPMs, which possibly affects the characteristics of acoustic energy and speech intelligibility. The objective of this study was to investigate the effect of RPMs on acoustic measurements through a systematic review with meta-analysis. METHODS: Five database searches were conducted, ranging from their inception to August 2023, as well as a manual search. Cross-sectional studies were included that provided data on widely used gender-independent clinical acoustic voice quality measures (jitter, shimmer, HNR, CPPS, and AVQI) and habitual sound pressure level (SPL). RESULTS: We found nine eligible research studies with a total of 422 participants who were compared both without masks and with different types of masks. All included studies focused on individuals with vocally healthy voices, while two of the studies also included those with voice disorders. The results from the meta-analysis were related to medical/surgical and FFP2/(K)N95 masks. None of the acoustic measurements showed significant differences between the absence and presence of masks (p > 0.05). When indirectly comparing both mask types, statistical significance was identified for parameters of jitter, HNR, CPPS and SPL (p < 0.001). CONCLUSIONS: The present meta-analysis indicates that certain types of RPMs have no significant influence on common voice quality parameters and SPL compared to recordings without masks. Nevertheless, it is plausible that significant differences in acoustic parameters might exist between different mask types. Consequently, it is advisable for the clinical practice to always use the same mask type when using RPMs to ensure high comparability and accuracy of measurement results.

Impact of etiology on disease course in chronic pancreatitis.

BACKGROUND: Complications in chronic pancreatitis (CP) can be grouped in inflammatory (ICC) and fibrotic (FCC) clusters and pancreatic insufficiency cluster (PIC). However, the association between etiological risk factors and the development of complication clusters remains obscure. In this study, the impact of the etiology and disease duration on disease onset and development of complications was investigated. METHODS: This cross-sectional study recruited patients with CP from Mannheim/Germany (n = 870), Gießen/Germany (n = 100) und Donetsk/Ukraine (n = 104). Etiological risk factors, disease stage, age at disease onset, complications, need for hospitalization and surgery were noted. RESULTS: In 1074 patients diagnosed with CP, main risk factors were alcohol and nicotine abuse. An earlier onset of the disease was observed upon nicotine abuse (-4.0 years). Alcohol abuse was only associated with an earlier onset of the definite stage of CP. Alcohol abuse was the major risk factor for the development of ICC (p < 0.0001, multiple regression modeling). Abstinence of alcohol reduced ICC, whereas abstinence of nicotine showed no association. PIC correlated with efferent duct abnormalities and the disease duration. In contrast, FCC was mainly dependent on the disease duration (p < 0.0001; t-test). The presence of any complication cluster correlated with the need for surgery (p < 0.01; X2-test). However, only ICC correlated with a prolonged hospital stay (p < 0.05; t-test). CONCLUSIONS: ICC is mainly dependent on alcohol abuse. In contrast, FCC and PIC are mainly dependent on the disease duration. The etiology and disease duration can be used as predictors of the course of disease to provide individual treatment and surveillance strategies.

Assessment and Evaluation of Psychosocial Distress in Outpatients with Cancer at a University Hospital in Germany.

INTRODUCTION: Cancer patients (pts) suffer from a significant amount of psychosocial distress related to tumor disease itself or straining treatments. Despite recommendations on how to screen for and to deal with psychosocial distress in cancer pts, data about implementation of psycho-oncological interventions (poi) in outpatient settings of cancer pts are scarce. The aim of this study was to identify outpatients with cancer in need of poi and to evaluate different assessment instruments. METHODS: N = 200 outpatients with hemat-/oncological malignancies were interviewed between October 2015 and December 2017 at the University Hospital Mannheim using the Basic Documentation for Psycho-Oncology (PO-Bado) and the Hornheider Screening Instrument (HSI) - both clinician-administered assessment tools - followed by descriptive, univariate, and agreement analysis. RESULTS: N = 61 cancer pts (31%) were identified to be in need for poi considering the results of both questionnaires. The number of identified pts in need of poi was lower when analyzing the results of the PO-Bado (n = 42, 21%) and the HSI (n = 39, 20%) separately. The degree of agreement between the results of PO-Bado and HSI was low (kappa = 0.3655). Several factors like gender, age and diagnosis were identified to have significant impact on the need for poi (p ≤ 0.05). CONCLUSION: Our study underlines that different screening instruments for psychosocial distress may identify disparate populations of cancer pts. The study data also revealed significant characteristics that might be associated with elevated levels of psychosocial distress and a clear indication for poi. However, further analyses on larger populations of cancer pts are needed to provide information how to transfer positive screening to poi in clinical routine.

Comparison of the DOAC Dipstick Test on Urine Samples With Chromogenic Substrate Methods on Plasma Samples in Outpatients Treated With Direct Oral Anticoagulants.

Identifying adherence to direct oral anticoagulants (DOACs) plays a major role in treatment efficacy and safety. The DOAC Dipstick can detect DOACs in urine samples of acutely diseased patients at plasma thresholds of about 30 ng/mL. A prospective observational consecutive cohort study was performed on outpatients taking DOACs. The presence of direct oral factor Xa inhibitors (DXIs) in patient urine samples were independently evaluated by visual interpretation of the DOAC Dipstick pad colors. DOAC plasma concentration was assessed using STA®-Liquid Anti-Xa and STA®-Liquid Anti-IIa chromogenic substrate assays. Positive DOAC Dipstick results were compared with a threshold plasma of DOAC concentration ≥30 ng/mL. Of 120 patients (age 55.4 + 16.1 years, female n = 63), 77 were on rivaroxaban and 43 on apixaban. Plasma concentrations were 129 ± 118 ng/mL for rivaroxaban, and 163 ± 130 ng/mL for apixaban, DOAC Dipstick test has a sensitivity of 97.2% and a positive predictive value of 89.5% at 30 ng/mL. No differences occurred between DXIs. Specificity and negative predictive value could not be determined due to the low number of true negative values. There were no differences in the interpretation of rivaroxaban and apixaban pad colors between observers (Kappa 1.0). Results show that DOAC Dipstick may be a useful tool for identifying DXIs in urine samples in an outpatient setting at a plasma threshold ≥ 30 ng/mL. Further studies should include patients treated with dabigatran, vitamin K antagonists, or other anticoagulants.