Intravenous Opioid Medication with Piritramide Reduces the Risk of Pneumothorax During CT-Guided Percutaneous Core Biopsy of the Lung.

PURPOSE: CT-guided percutaneous core biopsy of the lung is usually performed under local anesthesia, but can also be conducted under additional systemic opioid medication. The purpose of this retrospective study was to assess the effect of intravenous piritramide application on the pneumothorax rate and to identify risk factors for post-biopsy pneumothorax. MATERIALS AND METHODS: One hundred and seventy-one core biopsies of the lung were included in this retrospective single center study. The incidence of pneumothorax and chest tube placement was evaluated. Patient-, procedure- and target-related variables were analyzed by univariate and multivariable logistic regression analysis. RESULTS: The overall incidence of pneumothorax was 39.2% (67/171). The pneumothorax rate was 31.5% (29/92) in patients who received intravenous piritramide and 48.1% (38/79) in patients who did not receive piritramide. In multivariable logistic regression analysis periinterventional piritramide application proved to be the only independent factor to reduce the risk of pneumothorax (odds ratio 0.46, 95%-confidence interval 0.24, 0.88; p = 0.018). Two or more pleura passages (odds ratio 3.38, 95%-confidence interval: 1.15, 9.87; p = 0.026) and prone position of the patient (odds ratio 2.27, 95%-confidence interval: 1.04, 4.94; p = 0.039) were independent risk factors for a higher pneumothorax rate. CONCLUSION: Procedural opioid medication with piritramide proved to be a previously undisclosed factor decreasing the risk of pneumothorax associated with CT-guided percutaneous core biopsy of the lung. LEVEL OF EVIDENCE 4: small study cohort.

The translocator protein 18kDa ligand etifoxine in the treatment of depressive disorders-a double-blind, randomized, placebo-controlled proof-of-concept study.

BACKGROUND: Recent developments suggest that neurosteroids may achieve rapid antidepressant effects. As such, neurosteroidogenesis mediated by the translocator protein 18 kDa (TSPO) might constitute a promising option for the treatment of depression. Therefore, the current clinical trial aims to get the first evidence of whether TPSO ligands promote rapid antidepressant effects. Furthermore, we study which mechanisms of action, e.g., modulation of distinct neuronal networks, neurosteroidogenesis, endocrinological mechanisms, TSPO expression or microbiome composition, contribute to their putative antidepressant effects. METHODS: This is a randomized, placebo-controlled, double-blind single-center trial of 2-week treatment with the TSPO ligand etifoxine versus placebo in depressive patients. Main eligibility criteria: male or female individuals aged 18 to 65 years with unipolar/bipolar depressive disorder with no other psychiatric main diagnosis or acute neurological/somatic disorder or drug/alcohol dependence during their lifetime. The primary endpoint is the time point at which 50% of the maximal effect has occurred (ET50) estimated by the scores of the Hamilton Depression Scale (HAMD-21). A total of 20 patients per group are needed to detect changes of therapeutic efficacy about 5% and changes of ET50 about 10% with a power of 70%. Assuming a drop-out rate of 10-20%, 50 patients will be randomized in total. The study will be conducted at the Department of Psychiatry and Psychotherapy of the University of Regensburg. DISCUSSION: This study will provide a first proof-of-concept on the potential of the TSPO ligand etifoxine in the treatment of depressive disorders. TRIAL REGISTRATION: Clinical Trials Register (EudraCT number: 2021-006773-38 , registration date: 14 September 2022) and German Register of Clinical Studies (DRKS number: DRKS00031099 , registration date: 23 January 2023).

Temporal association of ventricular arrhythmias and respiratory events in heart failure patients with central sleep apnoea.

In contrast to obstructive sleep apnoea, the peak of sympathetic tone in central sleep apnoea occurs during the hyperventilation phase. To explore the temporal association of premature ventricular complex (PVC) burden in the context of the apnoea/hypopnoea-hyperpnoea cycle, the duration of apnoea/hypopnoea was defined as 100 %. We assessed the PVC burden throughout the apnoea/hypopnoea-hyperpnoea cycle during the periods of ±150 % in 50 % increments before and after the apnoea/hypopnoea phase. In this subanalysis of 54 SERVE-HF patients, PVC burden was 32 % higher in the late hyperventilation period (50-100 % after apnoea/hypopnoea) compared to the apnoea/hypopnoea phase.

The effects of Phoniatric PREhabilitation in Head and Neck Cancer patients on Aspiration and Preservation of Swallowing (PREHAPS): study protocol of a monocentric prospective randomized interventional outcome-blinded trial.

BACKGROUND: Dysphagia, with its negative impact on life expectancy and quality of life, is a major side effect of head and neck squamous cell carcinoma (HNSCC). In a typical Head and Neck Cancer Center, more than half of patients are affected. Improving treatment, and ideally prevention respectively prehabilitation, therefore seems more than desirable. METHODS: The study is planned as a monocentric, prospective, outcome-blinded, randomized interventional study comparing an advanced phoniatric-logopedic prehabilitation with a control (standard of care). Seventy patients (30 control group, 30 intervention group, 10 drop-out rate of 15%) with an initial diagnosis of invasive HNSCC and curative treatment intention will be included over a period of 17 months. In addition to the previous standard, both groups will undergo both detailed subjective assessment of swallowing function and quality of life by means of various questionnaires and objective analyses by bioelectrical impedance measurements and phoniatric endoscopic swallowing examinations. In the intervention group, risk-related nutritional counseling (face-to-face) and phoniatric-logopedic prehabilitation are provided: detailed counseling with video demonstration and exercises to strengthen and improve the range of motion of the oral, pharyngeal, and laryngeal muscles (guided by exercise diary). Controls are performed at 6 weeks, 3 and 6 months, and 9 or 12 months after the end of therapy during the regular tumor follow-up. Primary study endpoints are swallowing function and emotional distress at 6 weeks of control visit. DISCUSSION: Prehabilitation measures have already proven successful in other patient groups, e.g., transplant patients. In the field of head and neck oncology, interest in such concepts has increased significantly in recent years. However, usually, only subgroups, e.g., patients with swallowing problems after radiochemotherapy alone, are in focus. Our study aims to investigate the general benefit of prehabilitation with regard to swallowing function, which is so important for protection of aspiration and quality of life. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029676 . International Clinical Trials Registry Platform DRKS00029676 . Registered on 19 July 2022.

Clinical Characterization of Arrhythmia-Induced Cardiomyopathy in Patients With Tachyarrhythmia and Idiopathic Heart Failure.

BACKGROUND: Arrhythmia-induced cardiomyopathy (AIC) is a known entity, but prospective evidence for its characterization is limited. OBJECTIVES: This study aimed to: 1) determine the relative frequency of the pure form of AIC in the clinically relevant cohort of patients with newly diagnosed, otherwise unexplained left ventricular systolic dysfunction (LVSD) and tachyarrhythmia; 2) assess the time to recovery from LVSD; and 3) identify parameters for an early diagnosis of AIC. METHODS: Patients were prospectively included, underwent effective rhythm restoration, and were followed-up at 2, 4, and 6 months to evaluate clinical characteristics, biomarkers, and cardiac imaging including cardiac magnetic resonance imaging. Patients with recurred arrhythmia were excluded from analysis. RESULTS: 41 of 50 patients were diagnosed with AIC 6 months after rhythm restoration. Left ventricular (LV) ejection fraction increased 2 months after rhythm restoration from 35.4% ± 8.2% to 52.7% ± 8.0% in AIC patients vs 37.0% ± 9.5% to 43.3% ± 7.0% in non-AIC patients. From month 2 to 6, LV ejection fraction continued to increase in AIC patients (57.2% ± 6.1%; P < 0.001) but remained stable in non-AIC patients (44.0% ± 7.8%; P = 0.628). Multivariable logistic regression analysis revealed that lower LV end-diastolic diameter at baseline could be used for early diagnosis of AIC, whereas biomarkers and other morphological or functional parameters, including late LV gadolinium enhancement, did not show suitability for early diagnosis. CONCLUSIONS: We observed a high prevalence of AIC in patients with otherwise unexplained LVSD and concomitant tachyarrhythmia, suggesting that this condition may be underdiagnosed in clinical practice. Most patients recovered fast, within months, from LVSD. A low initial LV end-diastolic diameter may constitute an early marker for diagnosis of AIC.

Deep learning-based differentiation of peripheral high-flow and low-flow vascular malformations in T2-weighted short tau inversion recovery MRI.

BACKGROUND: Differentiation of high-flow from low-flow vascular malformations (VMs) is crucial for therapeutic management of this orphan disease. OBJECTIVE: A convolutional neural network (CNN) was evaluated for differentiation of peripheral vascular malformations (VMs) on T2-weighted short tau inversion recovery (STIR) MRI. METHODS: 527 MRIs (386 low-flow and 141 high-flow VMs) were randomly divided into training, validation and test set for this single-center study. 1) Results of the CNN's diagnostic performance were compared with that of two expert and four junior radiologists. 2) The influence of CNN's prediction on the radiologists' performance and diagnostic certainty was evaluated. 3) Junior radiologists' performance after self-training was compared with that of the CNN. RESULTS: Compared with the expert radiologists the CNN achieved similar accuracy (92% vs. 97%, p = 0.11), sensitivity (80% vs. 93%, p = 0.16) and specificity (97% vs. 100%, p = 0.50). In comparison to the junior radiologists, the CNN had a higher specificity and accuracy (97% vs. 80%, p <  0.001; 92% vs. 77%, p <  0.001). CNN assistance had no significant influence on their diagnostic performance and certainty. After self-training, the junior radiologists' specificity and accuracy improved and were comparable to that of the CNN. CONCLUSIONS: Diagnostic performance of the CNN for differentiating high-flow from low-flow VM was comparable to that of expert radiologists. CNN did not significantly improve the simulated daily practice of junior radiologists, self-training was more effective.

Clinical Value and Operational Risks of MRI in ICU patients - A Retrospective Analysis Performed at a University Medical Center.

PURPOSE: Intensive care unit (ICU) patients have a high risk of developing complications when leaving the ICU for diagnostic procedures or therapeutic interventions. Our study examined the frequency of adverse events associated with magnetic resonance imaging (MRI) of intensive care patients and the extent of changes in therapy due to the MRI scan to weigh the risks associated with the scan against the potential benefits of an MR scan, using a change in therapy as an indicator of benefit. MATERIALS AND METHODS: 4434 ICU patients (January to December 2015) were identified by Hospital Information System (SAP-R/3 IS-H, Walldorf, Germany), ICU patient data management system Metavision (iMDsoft, Israel), and Radiology Information System (Nexus.medRIS, Version 8.42, Nexus, Germany). All intensive care and medical records (HIS) and MRI reports (RIS) were matched and further evaluated in a retrospective case-to-case analysis for biometric data, mechanical ventilation, ICU requirements, planned postoperative vs. emergency diagnostic requirements, complications and impact on further diagnosis or therapy. RESULTS: Out of 4434 ICU patients, 322 ICU patients (7.3 %) underwent a total of 385 MRI examinations. 167 patients needed a total of 215 emergency scans, while 155 patients underwent 170 planned postoperative MRI exams. 158 (94.6 %) out of 167 emergency scan patients were ventilated under continuous intravenous medication and monitoring. In the planned postoperative group, only 6 (3.9 %) out of 155 were ventilated, but a total of 38 (24.5 %) were under continuous medication. 111 patients were accompanied by nurses only during MRI. Only one severe adverse event (0.3 %) was noted and was attributed to study preparation (n = 385). In 8 MRI examinations (2.1 %), the examination was interrupted or cancelled due to the patients' condition. While all MRI examinations in the planned group were completed (n = 170, 100 %) (e. g., postoperative controls), only 207 out of 215 (96.3 %) could be performed for emergency diagnostic reasons. MRI influenced the clinical course with a change in diagnosis or therapy in 74 (19.2 %) of all 385 MRI examinations performed, and in the emergency diagnostic group it was 31.2 % (n = 67/215). CONCLUSION: Nearly 20 % of MRI examinations of ICU patients resulted in a change of therapy. With only one potentially life-threatening adverse event (0.3 %) during transport and the MRI examination, the risk seems to be outweighed by the diagnostic benefit. KEY POINTS: · The risk of adverse events associated with MRI scans in ICU patients is low.. · The rate of premature termination of ICU patients' MRI scans is low.. · Almost 20 % of ICU patients' MRI scans lead to a change of therapy..

Better early outcome with enhanced recovery total hip arthroplasty (ERAS-THA) versus conventional setup in randomized clinical trial (RCT).

INTRODUCTION: Numbers of total hip arthroplasty (THA) are steadily rising and patients expect faster mobility without pain postoperatively. The aim of enhanced recovery after Surgery (ERAS) programs in a multidisciplinary setup was to keep pace with the needs of quality and quantity of surgical THA-interventions and patients' expectations. METHODS: 194 patients undergoing THA procedures were investigated after single-blinded randomization to ERAS (98) or conventional setup group (96). Primary outcome variable was mobilization measured with the Timed Up and Go Test (TUG) in seconds. Secondary outcome variables were floor count and walking distance in meters as well as rest, mobilization and night pain on a numerous rating scale (NRS). All variables were recorded preoperatively and daily until the sixth postoperative day. To assess and compare clinical outcome and patient satisfaction, the PPP33-Score and PROMs were used. RESULTS: No complications such as thromboembolic complications, fractures or revisions were recorded within the first week postoperatively in either study group. Compared to the conventional group, the ERAS group showed significantly better TUG (p < 0.050) and walking distance results after surgery up to the sixth, and floor count up to the third postoperative day. On the first and second postoperative day, ERAS patients showed superior results (p < 0.001) in all independent activity subitems. Regarding the evaluation of pain (NRS), PPP33 and PROMS, no significant difference was shown (p > 0.050). CONCLUSION: This prospective single-blinded randomized controlled clinical trial was able to demonstrate excellent outcome with comparable pain after ERAS THA versus a conventional setup. Therefore, ERAS could be used in daily clinical practice.

Prevalence and Risk Factors for Weaning Failure From Venovenous Extracorporeal Membrane Oxygenation in Patients With Severe Acute Respiratory Insufficiency.

OBJECTIVE: Analysis of the prevalence and risk factors for weaning failure from venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory insufficiency. DESIGN: Single-center retrospective observational study. SETTING: Sixteen beds medical ICU at the University Hospital Regensburg. PATIENTS: Two hundred twenty-seven patients with severe acute respiratory insufficiency requiring VV-ECMO support between October 2011 and December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients meeting our ECMO weaning criteria (Sp o2 ≥ 90% with F io2 ≤ 0.4 or Pa o2 /F io2 > 150 mm Hg, pH = 7.35-7.45, positive end-expiratory pressure ≤ 10 cm H 2 O, driving pressure < 15 cm H 2 O, respiratory rate < 30/min, tidal volume > 5 mL/kg, ECMO bloodflow ≈ 1. 5 L/min, sweep gas flow ≈ 1 L/min, heart rate < 120/min, systolic blood pressure 90-160 mm Hg, norepinephrine < 0.2 µg/[kg*min]) underwent an ECMO weaning trial (EWT) with pausing sweep gas flow. Arterial blood gas analysis, respiratory and ventilator parameters were recorded prior, during, and after EWTs. Baseline data, including demographics, vitals, respiratory, ventilator, and laboratory parameters were recorded at the time of cannulation. One hundred seventy-nine of 227 (79%) patients were successfully decannulated. Ten patients (4%) underwent prolonged weaning of at least three failed EWTs before successful decannulation. The respiratory rate (19/min vs 16/min, p = 0.002) and Pa co2 (44 mm Hg vs 40 mm Hg, p = 0.003) were higher before failed than successful EWTs. Both parameters were risk factors for ECMO weaning failure (Pa co2 : odds ratio [OR] 1.05; 95% CI, 1.001-1.10; p = 0.045; respiratory rate: OR 1.10; 95% CI, 1.04-1.15; p < 0.001) in multivariable analysis. The rapid shallow breathing index [42 (1/L*min), vs 35 (1/L*min), p = 0.052) was higher before failed than successful EWTs. The decline of Sa o2 and Pa o2 /F io2 during EWTs was higher in failed than successful trials. CONCLUSIONS: Seventy-nine percent of patients were successfully decannulated with only 4% needing prolonged ECMO weaning. Before EWT only parameters of impaired ventilation (insufficient decarboxylation, higher respiratory rate) but not of oxygenation were predictive for weaning failure, whereas during EWT-impaired oxygenation was associated with weaning failure.

Diagnosis of sarcopenia on thoracic computed tomography and its association with postoperative survival after anatomic lung cancer resection.

Computer tomography-derived skeletal muscle index normalized for height in conjunction with muscle density enables single modality-based sarcopenia assessment that accounts for all diagnostic criteria and cutoff recommendations as per the widely accepted European consensus. Yet, the standard approach to quantify skeletal musculature at the third lumbar vertebra is limited for certain patient groups, such as lung cancer patients who receive chest CT for tumor staging that does not encompass this lumbar level. As an alternative, this retrospective study assessed sarcopenia in lung cancer patients treated with curative intent at the tenth thoracic vertebral level using appropriate cutoffs. We showed that skeletal muscle index and radiation attenuation at level T10 correlate well with those at level L3 (Pearson's R = 0.82 and 0.66, p < 0.001). During a median follow-up period of 55.7 months, sarcopenia was independently associated with worse overall (hazard ratio (HR) = 2.11, 95%-confidence interval (95%-CI) = 1.38-3.23, p < 0.001) and cancer-specific survival (HR = 2.00, 95%-CI = 1.19-3.36, p = 0.009) of lung cancer patients following anatomic resection. This study highlights feasibility to diagnose sarcopenia solely by thoracic CT in accordance with the European consensus recommendations. The straightforward methodology offers easy translation into routine clinical care and potential to improve preoperative risk stratification of lung cancer patients scheduled for surgery.

Predictors of Nocturnal Hypoxemic Burden in Patients Undergoing Elective Coronary Artery Bypass Grafting Surgery.

Background: Nocturnal hypoxemia has been linked to increased cardiovascular morbidity and mortality. Several common diseases, such as sleep-disordered breathing (SDB), heart failure (HF), obesity, and pulmonary disease, coincide with an elevated nocturnal hypoxemic burden with and without repetitive desaturations. Research question: This study aimed to evaluate the association of relevant common diseases with distinctive metrics of nocturnal hypoxemic burden with and without repetitive desaturations in patients undergoing coronary artery bypass grafting surgery. Study design and methods: In this subanalysis of the prospective observational study, CONSIDER-AF (NCT02877745) portable SDB monitoring was performed on 429 patients with severe coronary artery disease the night before cardiac surgery. Pulse oximetry was used to determine nocturnal hypoxemic burden, as defined by total recording time spent with oxygen saturation levels < 90% (T90). T90 was further characterized as T90 due to intermittent hypoxemia (T90desaturation) and T90 due to nonspecific and noncyclic SpO2-drifts (T90non-specific). Results: Multivariable linear regression analysis identified SDB (apnea-hypopnea-index ≥ 15/h; B [95% CI]: 6.5 [0.4; 12.5], p = 0.036), obesity (8.2 [2.5; 13.9], p = 0.005), and mild-to-moderate chronic obstructive pulmonary disease (COPD, 16.7 [8.5; 25.0], p < 0.001) as significant predictors of an increased nocturnal hypoxemic burden. Diseases such as SDB, obesity and HF were significantly associated with elevated T90desaturation. In contrast, obesity and mild-to-moderate COPD were significant modulators of T90non-specific. Interpretation: SDB and leading causes for SDB, such as obesity and HF, are associated with an increased nocturnal hypoxemic burden with repetitive desaturations. Potential causes for hypoventilation syndromes, such as obesity and mild-to-moderate COPD, are linked to an increased hypoxemic burden without repetitive desaturations. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02877745.

Volume-Assisted Estimation of Remnant Liver Function Based on Gd-EOB-DTPA Enhanced MR Relaxometry: A Prospective Observational Trial.

In the context of liver surgery, predicting postoperative liver dysfunction is essential. This study explored the potential of preoperative liver function assessment by MRI for predicting postoperative liver dysfunction and compared these results with the established indocyanine green (ICG) clearance test. This prospective study included patients undergoing liver resection with preoperative MRI planning. Liver function was quantified using T1 relaxometry and correlated with established liver function scores. The analysis revealed an improved model for predicting postoperative liver dysfunction, exhibiting an accuracy (ACC) of 0.79, surpassing the 0.70 of the preoperative ICG test, alongside a higher area under the curve (0.75). Notably, the proposed model also successfully predicted all cases of liver failure and showed potential in predicting liver synthesis dysfunction (ACC 0.78). This model showed promise in patient survival rates with a Hazard ratio of 0.87, underscoring its potential as a valuable tool for preoperative evaluation. The findings imply that MRI-based assessment of liver function can provide significant benefits in the early identification and management of patients at risk for postoperative liver dysfunction.

Assessment of the quality of different commercial providers using artificial intelligence for automated cephalometric analysis compared to human orthodontic experts.

PURPOSE: The aim of this investigation was to evaluate the accuracy of various skeletal and dental cephalometric parameters as produced by different commercial providers that make use of artificial intelligence (AI)-assisted automated cephalometric analysis and to compare their quality to a gold standard established by orthodontic experts. METHODS: Twelve experienced orthodontic examiners pinpointed 15 radiographic landmarks on a total of 50 cephalometric X­rays. The landmarks were used to generate 9 parameters for orthodontic treatment planning. The "humans' gold standard" was defined by calculating the median value of all 12 human assessments for each parameter, which in turn served as reference values for comparisons with results given by four different commercial providers of automated cephalometric analyses (DentaliQ.ortho [CellmatiQ GmbH, Hamburg, Germany], WebCeph [AssembleCircle Corp, Seongnam-si, Korea], AudaxCeph [Audax d.o.o., Ljubljana, Slovenia], CephX [Orca Dental AI, Herzliya, Israel]). Repeated measures analysis of variances (ANOVAs) were calculated and Bland-Altman plots were generated for comparisons. RESULTS: The results of the repeated measures ANOVAs indicated significant differences between the commercial providers' predictions and the humans' gold standard for all nine investigated parameters. However, the pairwise comparisons also demonstrate that there were major differences among the four commercial providers. While there were no significant mean differences between the values of DentaliQ.ortho and the humans' gold standard, the predictions of AudaxCeph showed significant deviations in seven out of nine parameters. Also, the Bland-Altman plots demonstrate that a reduced precision of AI predictions must be expected especially for values attributed to the inclination of the incisors. CONCLUSION: Fully automated cephalometric analyses are promising in terms of timesaving and avoidance of individual human errors. At present, however, they should only be used under supervision of experienced clinicians.

Intraoperative suggestions to prevent postoperative delirium in patients undergoing transaortic valvular replacement: a randomized placebo-controlled trial.

BACKGROUND: Postoperative delirium (POD) is a serious complication following anaesthesia and surgery and significantly influences postoperative outcome especially in the elderly population. Intraoperative music and positive suggestions influence postoperative outcomes by attenuating analgesic demand and increasing patient satisfaction. AIMS: Here, we examined the effect of intraoperative music and positive suggestions on the development of POD in aged patients undergoing transcatheter aortic valve replacement (TAVR) procedure under general anaesthesia. METHODS: For this randomized placebo-controlled study, eligible patients without cognitive deficit, indicated by a MMSE < 10 points, were anesthetized using remifentanil and sevoflurane. Anaesthetic depth was guide with bispectral index. An audiotape with positive suggestions was applied from a MP3 player via headphones. POD, pain and PONV was assessed. CAM-ICU and Nu-DESC were done twice daily for the first 5 days. RESULTS: Of 140 patients 118 patients could be analysed (57 male, 80.6 ± 5.1 years). POD was diagnosed in 16 patients (12.7%). POD was significantly more often observed in male (12, 21.1%) than in female (4, 6.6%, p = 0.02) and in patients with a low MMSE (23.6 ± 4.5 vs. 26.8 ± 2.8, p = 0.001). Anaesthetic depth did not influence the incidence of POD. Intraoperative music and suggestions did not affect the rate of POD, pain, analgesic requirement or PONV. DISCUSSION: In patients undergoing TAVR male sex and low MMSE scoring are associated with an increase in POD. CONCLUSIONS: Intraoperative music and positive suggestions do not influence the incidence of POD in this patient group. STUDY REGISTRATION: DRKS: 00024444, start of registration: 4.02.202, final registration: 17.09.2021.

Analysis of long-term mortality after total body irradiation-based and melphalan-based chemotherapy conditioning for acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for selected patients with acute myeloid leukemia. Yet, the influence of total body irradiation (TBI)-based conditioning as compared to non-TBI-based conditioning on long-term mortality is unclear. We retrospectively evaluated outcomes after TBI-based (n = 91) and non-TBI-based conditioning (melphalan-based, n = 248) for 1st allo-HSCT patients transplanted at the University Hospital Regensburg between 1999 and 2020. TBI was performed with an average dose rate of 4 cGy/min. Median follow-up was 8.3 years (interquartile range, 4.8-12.9 years). Cumulative incidence rates of 5-year non-relapse mortality (NRM) were 17% (95% confidence interval, CI, 10-25) and 33% (95% CI, 27-40) after TBI- and non-TBI-based conditioning (P < 0.001). Five-year cumulative incidences of relapse (CIR) were 42% (95% CI, 32-52) and 29% (95% CI, 23-35) after TBI- and non-TBI-based conditioning (P = 0.030). The 5-year OS was 54% (95% CI, 43-64) and 55% (95% CI, 48-62) after TBI- and non-TBI-based conditioning. Both groups had similar 100-day acute graft-versus-host disease (aGVHD, 43% vs. 40%) and 5-year chronic GVHD (34% vs. 36%). The multivariable regression models found no associations of TBI with the outcomes NRM, CIR, PFS, OS, aGVHD, and cGVHD. TBI was no risk factor for NRM, even including mortality caused by secondary malignancies. NRM was influenced by patient age, advanced disease status, and the use of female donors for male recipients. TBI- and non-TBI-based conditioning appear to be equally effective and tolerable for AML patients eligible for 1st allo-HSCT.

Isokinetic knee muscle strength comparison after enhanced recovery after surgery (ERAS) versus conventional setup in total knee arthroplasty (TKA): a single blinded prospective randomized study.

PURPOSE: Total knee arthroplasty (TKA) combined with the concept of enhanced recovery is of continued worldwide interest, as it is reported to improve early functional outcome and treatment quality without increasing complications. The aim of the study was to investigate isokinetic knee muscle strength after cemented TKA in combination with an enhanced recovery after surgery (ERAS) compared to a conventional setup. METHODS: In the single blinded prospective randomized study, 52 patients underwent navigated primary cemented TKA within an ERAS (n = 30) or a conventional setup (n = 22). Preoperatively, five days and four weeks after surgery isokinetic knee muscle strength with BIODEX-type measuring device (peak torque in Nm, work in Joules and power in Watt) and subjective patient-related outcome measures (PROMs) were investigated. RESULTS: The ERAS group showed significantly better outcomes in knee flexion at 180°/s (peak torque (Nm) p = 0.047, work (J) p = 0.040 and power (W) p = 0.016) 5 days postoperatively. The isokinetic measuring at knee extension 60°/s and 180°/s demonstrated no significant difference. The PROMs showed that patients were satisfied with the postoperative results in both groups. After 4 weeks, there was no longer a significant difference in isokinetic measuring at knee extension and flexion between the ERAS and conventional group. CONCLUSIONS: TKA with the concept of ERAS improves excellent isokinetic outcome and patient satisfaction. The isokinetic muscle strength measurement can help patients and surgeons to modify expectations and improve patient satisfaction.

Regional Differences in Waiting Times for Kidney Transplantation in Germany.

BACKGROUND: In order to achieve short ischemia times between organ donation and transplantation, regional organ allocation has been assigned priority in the development of allocation rules for kidney transplantation. It is unclear whether this leads to differences in regional waiting times in Germany. METHODS: A retrospective cohort study over a 24-month observation period was conducted, including all patients who received a kidney-only graft allocated via the standard Eurotransplant Kidney Allocation System (ETKAS) (n = 1487) or the Eurotransplant Senior Program (ESP) (n = 566). Multiple linear regression analyses were performed to investigate differences in waiting times across the regions (ETKAS) or subregions (ESP) as defined by the German Organ Procurement Organization (DSO). Associations between the number of regionally procured kidneys (n = 1444) and regional waiting times were investigated. RESULTS: In ETKAS, the median waiting time was 8.9 years (interquartile range [IQR] 6.7-10.6); in ESP, it was 3.9 (2.4 -5.3) years. Compared with the reference region with the shortest waiting time, waiting times in other regions were 0.6 to 1.7 years longer in ETKAS and 1.3 to 4.4 years longer in ESP. The ratio of the number of patients on the waiting list for a particular region to the number of organs donated in that region was associated with the waiting time in ETKAS (R2 = 0.70). In ESP, this association was markedly less pronounced (R2 = 0.45). CONCLUSION: In Germany, waiting times depend strongly on the region where a patient is listed for kidney transplantation, especially in ESP. These findings call the current allocation algorithms into question and imply a need for suitable modification.

Precise Monitoring of Returning Sensation in Digital-Nerve Lesions by Three-Dimensional Imaging: A Proof-of-Concept Study.

SUMMARY: Digital-nerve lesions result in a loss of tactile sensation reflected by an anesthetic area (AA) at the radial or ulnar aspect of the respective digit. Available tools to monitor the recovery of tactile sense have been criticized for their lack of validity. Precise quantification of AA dynamics by three-dimensional (3D) imaging could serve as an accurate surrogate to monitor recovery after digital-nerve repair. For validation, AAs were marked on digits of healthy volunteers to simulate the AA of an impaired cutaneous innervation. The 3D models were composed from raw images that had been acquired with a 3D camera to precisely quantify relative AA for each digit (3D models, n = 80). Operator properties varied with regard to individual experience in 3D imaging and image processing. In addition, the concept was applied in a clinical case study. Results showed that images taken by experienced photographers were rated as better quality ( P < 0.001) and needed less processing time ( P = 0.020). Quantification of the relative AA was not altered significantly, regardless of experience level of the photographer ( P = 0.425) or image assembler ( P = 0.749). The proposed concept allows precise and reliable surface quantification of digits and can be performed consistently without relevant distortion by lack of examiner experience. Routine 3D imaging of the AA has the great potential to provide visual evidence of various returning states of sensation and to convert sensory nerve recovery into a metric variable with high responsiveness to temporal progress.

Expression of pH-Sensitive GPCRs in Peritoneal Carcinomatosis of Colorectal Cancer-First Results.

Solid tumors have an altered metabolism with a so-called inside-out pH gradient (decreased pHe < increased pHi). This also signals back to tumor cells via proton-sensitive ion channels or G protein-coupled receptors (pH-GPCRs) to alter migration and proliferation. Nothing, however, is known about the expression of pH-GPCRs in the rare form of peritoneal carcinomatosis. Paraffin-embedded tissue samples of a series of 10 patients with peritoneal carcinomatosis of colorectal (including appendix) origin were used for immunohistochemistry to study the expression of GPR4, GPR65, GPR68, GPR132, and GPR151. GPR4 was just expressed weakly in 30% of samples and expression was significantly reduced as compared to GPR56, GPR132, and GPR151. Furthermore, GPR68 was only expressed in 60% of tumors and showed significantly reduced expression as compared to GPR65 and GPR151. This is the first study on pH-GPCRs in peritoneal carcinomatosis, which shows lower expression of GPR4 and GPR68 as compared to other pH-GPCRs in this type of cancer. It may give rise to future therapies targeting either the TME or these GPCRs directly.