Irinotecan and temozolomide in combination with dasatinib and rapamycin versus irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma (RIST-rNB-2011): a multicentre, open-label, randomised, controlled, phase 2 trial.

BACKGROUND: Neuroblastoma is the most common extracranial solid tumour in children. Relapsed or refractory neuroblastoma is associated with a poor outcome. We assessed the combination of irinotecan-temozolomide and dasatinib-rapamycin (RIST) in patients with relapsed or refractory neuroblastoma. METHODS: The multicentre, open-label, randomised, controlled, phase 2, RIST-rNB-2011 trial recruited from 40 paediatric oncology centres in Germany and Austria. Patients aged 1-25 years with high-risk relapsed (defined as recurrence of all stage IV and MYCN amplification stages, after response to treatment) or refractory (progressive disease during primary treatment) neuroblastoma, with Lansky and Karnofsky performance status at least 50%, were assigned (1:1) to RIST (RIST group) or irinotecan-temozolomide (control group) by block randomisation, stratified by MYCN status. We compared RIST (oral rapamycin [loading 3 mg/m2 on day 1, maintenance 1 mg/m2 on days 2-4] and oral dasatinib [2 mg/kg per day] for 4 days with 3 days off, followed by intravenous irinotecan [50 mg/m2 per day] and oral temozolomide [150 mg/m2 per day] for 5 days with 2 days off; one course each of rapamycin-dasatinib and irinotecan-temozolomide for four cycles over 8 weeks, then two courses of rapamycin-dasatinib followed by one course of irinotecan-temozolomide for 12 weeks) with irinotecan-temozolomide alone (with identical dosing as experimental group). The primary endpoint of progression-free survival was analysed in all eligible patients who received at least one course of therapy. The safety population consisted of all patients who received at least one course of therapy and had at least one post-baseline safety assessment. This trial is registered at ClinicalTrials.gov, NCT01467986, and is closed to accrual. FINDINGS: Between Aug 26, 2013, and Sept 21, 2020, 129 patients were randomly assigned to the RIST group (n=63) or control group (n=66). Median age was 5·4 years (IQR 3·7-8·1). 124 patients (78 [63%] male and 46 [37%] female) were included in the efficacy analysis. At a median follow-up of 72 months (IQR 31-88), the median progression-free survival was 11 months (95% CI 7-17) in the RIST group and 5 months (2-8) in the control group (hazard ratio 0·62, one-sided 90% CI 0·81; p=0·019). Median progression-free survival in patients with amplified MYCN (n=48) was 6 months (95% CI 4-24) in the RIST group versus 2 months (2-5) in the control group (HR 0·45 [95% CI 0·24-0·84], p=0·012); median progression-free survival in patients without amplified MYCN (n=76) was 14 months (95% CI 9-7) in the RIST group versus 8 months (4-15) in the control group (HR 0·84 [95% CI 0·51-1·38], p=0·49). The most common grade 3 or worse adverse events were neutropenia (54 [81%] of 67 patients given RIST vs 49 [82%] of 60 patients given control), thrombocytopenia (45 [67%] vs 41 [68%]), and anaemia (39 [58%] vs 38 [63%]). Nine serious treatment-related adverse events were reported (five patients given control and four patients given RIST). There were no treatment-related deaths in the control group and one in the RIST group (multiorgan failure). INTERPRETATION: RIST-rNB-2011 demonstrated that targeting of MYCN-amplified relapsed or refractory neuroblastoma with a pathway-directed metronomic combination of a multkinase inhibitor and an mTOR inhibitor can improve progression-free survival and overall survival. This exclusive efficacy in MYCN-amplified, relapsed neuroblastoma warrants further investigation in the first-line setting. FUNDING: Deutsche Krebshilfe.

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.

Nocturnal hypoxemic burden and micro- and macrovascular disease in patients with type 2 diabetes.

BACKGROUND: Micro- and macrovascular diseases are common in patients with type 2 diabetes mellitus (T2D) and may be partly caused by nocturnal hypoxemia. The study aimed to characterize the composition of nocturnal hypoxemic burden and to assess its association with micro- and macrovascular disease in patients with T2D. METHODS: This cross-sectional analysis includes overnight oximetry from 1247 patients with T2D enrolled in the DIACORE (DIAbetes COhoRtE) study. Night-time spent below a peripheral oxygen saturation of 90% (T90) as well as T90 associated with non-specific drifts in oxygen saturation (T90non - specific), T90 associated with acute oxygen desaturation (T90desaturation) and desaturation depths were assessed. Binary logistic regression analyses adjusted for known risk factors (age, sex, smoking status, waist-hip ratio, duration of T2D, HbA1c, pulse pressure, low-density lipoprotein, use of statins, and use of renin-angiotensin-aldosterone system inhibitors) were used to assess the associations of such parameters of hypoxemic burden with chronic kidney disease (CKD) as a manifestation of microvascular disease and a composite of cardiovascular diseases (CVD) reflecting macrovascular disease. RESULTS: Patients with long T90 were significantly more often affected by CKD and CVD than patients with a lower hypoxemic burden (CKD 38% vs. 28%, p < 0.001; CVD 30% vs. 21%, p < 0.001). Continuous T90desaturation and desaturation depth were associated with CKD (adjusted OR 1.01 per unit, 95% CI [1.00; 1.01], p = 0.008 and OR 1.30, 95% CI [1.06; 1.61], p = 0.013, respectively) independently of other known risk factors for CKD. For CVD there was a thresholdeffect, and only severly and very severly increased T90non-specific was associated with CVD ([Q3;Q4] versus [Q1;Q2], adjusted OR 1.51, 95% CI [1.12; 2.05], p = 0.008) independently of other known risk factors for CVD. CONCLUSION: While hypoxemic burden due to oxygen desaturations and the magnitude of desaturation depth were significantly associated with CKD, only severe hypoxemic burden due to non-specific drifts was associated with CVD. Specific types of hypoxemic burden may be related to micro- and macrovascular disease.

NaV1.8 as Proarrhythmic Target in a Ventricular Cardiac Stem Cell Model.

The sodium channel NaV1.8, encoded by the SCN10A gene, has recently emerged as a potential regulator of cardiac electrophysiology. We have previously shown that NaV1.8 contributes to arrhythmogenesis by inducing a persistent Na+ current (late Na+ current, INaL) in human atrial and ventricular cardiomyocytes (CM). We now aim to further investigate the contribution of NaV1.8 to human ventricular arrhythmogenesis at the CM-specific level using pharmacological inhibition as well as a genetic knockout (KO) of SCN10A in induced pluripotent stem cell CM (iPSC-CM). In functional voltage-clamp experiments, we demonstrate that INaL was significantly reduced in ventricular SCN10A-KO iPSC-CM and in control CM after a specific pharmacological inhibition of NaV1.8. In contrast, we did not find any effects on ventricular APD90. The frequency of spontaneous sarcoplasmic reticulum Ca2+ sparks and waves were reduced in SCN10A-KO iPSC-CM and control cells following the pharmacological inhibition of NaV1.8. We further analyzed potential triggers of arrhythmias and found reduced delayed afterdepolarizations (DAD) in SCN10A-KO iPSC-CM and after the specific inhibition of NaV1.8 in control cells. In conclusion, we show that NaV1.8-induced INaL primarily impacts arrhythmogenesis at a subcellular level, with minimal effects on systolic cellular Ca2+ release. The inhibition or knockout of NaV1.8 diminishes proarrhythmic triggers in ventricular CM. In conjunction with our previously published results, this work confirms NaV1.8 as a proarrhythmic target that may be useful in an anti-arrhythmic therapeutic strategy.

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.

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.

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.

Expression of pH-Sensitive TRPC4 in Common Skin Tumors.

TRPCs (transient receptor potential classical or cation channels) play a crucial role in tumor biology, especially in the Ca2+ homeostasis in cancer cells. TRPC4 is a pH-sensitive member of this family of proteins. As solid tumors exhibit an inversed pH-gradient with lowered extracellular and increased intracellular pH, both contributing to tumor progression, TRPC4 might be a signaling molecule in the altered tumor microenvironment. This is the first study to investigate the expression profiles of TRPC4 in common skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM) and nevus cell nevi (NCN). We found that all SCCs, NCNs, and MMs show positive TRPC4-expression, while BCCs do only in about half of the analyzed samples. These data render TRPC4 an immunohistochemical marker to distinguish SCC and BCC, and this also gives rise to future studies investigating the role of TRPC4 in tumor progression, and especially metastasis as BCCs very rarely spread and are mostly negative for TRPC4.

The throwing shoulder in youth elite handball: adaptions of inferior but not anterior capsule thickness differ between the two sexes.

The aim was to investigate side-to-side and sex differences of anterior and inferior capsule thickness (ACT, ICT) between the throwing and non-throwing shoulder (TS, NTS) in youth elite handball players. 125 youth female and male elite handball players (14.1±0.7yo) were assessed for ACT and ICT by ultrasound . ACT measurement was performed from anterior (3 o'clock) in upright position and for ICT from inferior (6 o'clock) in supine position. Measurements of ICT in the TS of all athletes (1.4±0.2 mm) differed significantly but marginally to those in the NTS (1.3±0.2 mm) (p = 0.001). Female (1.2±0.2 mm vs. 1.3±0.2 mm; p = 0.007) but not male youth players (1.4±0.2 mm vs. 1.4±0.2 mm, p = n.s.) demonstrated slight differences in ICT in the TS compared with the NTS. Although significant, the thickness in the TS compared to the NTS was within the measurement accuracy of the ultrasonic assessment. No difference in ACT was observed in the TS (1.4±0.3 mm) compared to the NTS (1.4±0.3 mm) for both sexes (n.s.).In conclusion, the anterior and inferior capsule thickness in youth elite handball athletes is not or only marginally different between throwing and non-throwing shoulders.

Immunity after COVID-19 and vaccination: follow-up study over 1 year among medical personnel.

BACKGROUND: The long-term course of immunity among individuals with a history of COVID-19, in particular among those who received a booster vaccination, has not been well defined so far. METHODS: SARS-CoV-2-specific antibody levels were measured by ELISA over 1 year among 136 health care workers infected during the first COVID-19 wave and in a subgroup after booster vaccination approximately 1 year later. Furthermore, spike-protein-reactive memory T cells were quantified approximately 7 months after the infection and after booster vaccination. Thirty healthy individuals without history of COVID-19 who were routinely vaccinated served as controls. RESULTS: Levels of SARS-CoV-2-specific IgM- and IgA-antibodies showed a rapid decay over time, whereas IgG-antibody levels decreased more slowly. Among individuals with history of COVID-19, booster vaccination induced very high IgG- and to a lesser degree IgA-antibodies. Antibody levels were significantly higher after booster vaccination than after recovery from COVID-19. After vaccination with a two-dose schedule, healthy control subjects developed similar antibody levels as compared to individuals with history of COVID-19 and booster vaccination. SARS-CoV-2-specific memory T cell counts did not correlate with antibody levels. None of the study participants suffered from a reinfection. CONCLUSIONS: Booster vaccination induces high antibody levels in individuals with a history of COVID-19 that exceeds by far levels observed after recovery. SARS-CoV-2-specific antibody levels of similar magnitude were achieved in healthy, COVID-19-naïve individuals after routine two-dose vaccination.

Impact of chronic kidney disease on the outcomes of infrapopliteal venous, and heparin-bonded expanded polytetrafluoroethylene bypass surgeries: A retrospective cohort study.

The aim of this study was to analyze the results of infrapopliteal venous and prosthetic bypass surgeries for patients with chronic limb-threatening ischemia (CLTI) and moderate to severe chronic kidney disease (CKD). All consecutive patients undergoing infrapopliteal bypass surgeries at two academic vascular centers between March 2002 and November 2018 were included in this retrospective study. During this timeframe, infrapopliteal grafts were performed for 487 patients. Of these patients, 160 (32.9%; group 1) had normal renal function, 248 (50.9%; group 2) had moderate CKD, and 79 (16.2%; group 3) had severe CKD according to the Kidney Disease Improving Global Outcomes guidelines. After 5 years' follow-up, the primary patency rate was 46.0% and the secondary patency rate was 54.9% without statistical significance noted between the CKD groups. Limb salvage (65.3%, p = 0.024) and long-term survival (19.6%, p < 0.001) were considerably lower in patients with severe CKD. In subgroup analysis, vein grafts had significantly better long-term patency rates compared to prosthetic grafts, regardless of CKD group. However, in patients with severe CKD, patency rates of vein and heparin-bonded expanded polytetrafluoroethylene (HePTFE) grafts were comparable at the 1-year mark. Our study shows that autologous vein grafts remain the first choice for infrapopliteal bypass surgeries in patients with CKD. HePTFE grafts showed good short-term results in patients with severe CKD. Given the short life expectancy of these high-risk patients, prosthetic HePTFE grafts may be reasonable in this population if a suitable vein is absent.

Higher risk of ACL rupture in amateur football compared to professional football: 5-year results of the 'Anterior cruciate ligament-registry in German football'.

PURPOSE: Anterior cruciate ligament (ACL) injuries are a common severe type of football injury at all levels of play. A football-specific ACL registry providing both prospective ACL injury data according to the skill level and risk factors for ACL injury is lacking in the literature. METHODS: This study is based on the prospective 'ACL registry in German Football' implemented in the 2014-15 season. Professional (1st-3rd league), semi-professional (4th-6th league) and amateur leagues (7th league) were analysed regarding the incidence and risk factors for ACL injuries. Injuries were registered according to the direct reports of the injured players to the study office and double-checked via media analysis. After injury registration, the players received a standardised questionnaire. Data were analysed from the 2014-15 to the 2018-19 football season. RESULTS: Overall, 958 ACL injuries were registered during the 5-year study period. The incidence of ACL injuries was highest in amateur football (0.074/1000 h football exposure) compared to professional (0.058/1000 h; p < 0.0001) and semi-professional football (0.043/1000 h; p < 0.0001). At all skill levels, match incidence (professional: 0.343; semi-professional: 0.249; amateur: 0.319) was significantly higher than training incidence (professional: 0.015; semi-professional: 0.004; amateur: 0.005). Major risk factors were previous ACL injury (mean: 23.3%), other knee injuries (mean: 19.3%) and move to a higher league (mean: 24.2%). CONCLUSION: This sports-specific ACL registry provides detailed information on the incidence and risk factors for ACL injuries in football over five years. Risk factors are skill level, match exposure, move to a higher league and previous knee injury. These factors offer potential starting points for screening at-risk players and applying targeted prevention. LEVEL OF EVIDENCE: II.

Comparison of venous couplers versus hand-sewn technique in 4577 cases of DIEP-flap breast reconstructions - A multicenter study.

INTRODUCTION: Venous anastomosis remains to be a challenging step in microsurgical tissue transfer and venous complications constitute to a common reason for free flap failure. While several studies have compared mechanical vs. hand-sewn venous anastomoses, there is no large-series study comparing the type of anastomosis exclusively in DIEP flap breast reconstructions. PATIENTS AND METHODS: Between 2011 and 2019, 3926 female patients underwent 4577 free DIEP-flap breast reconstructions in 22 different breast cancer centers. Patient data was collected via an online database, files were screened and cases were divided into a hand- (HA) and a coupler-anastomosis (CA) group. Complications were accounted for and the two groups were then compared. RESULTS: Mean ischemia time was significantly shorter in the CA group (46.88 ± 26.17 vs. 55.48 ± 24.70 min; p < .001), whereas mean operative time was comparable (316 ± 134.01 vs. 320.77 ± 120.29 minutes; p = .294). We found no significant difference between both groups regarding the rate of partial (CA: 1.0% vs. HA: 1.3%) and total flap loss (CA: 2.2% vs. HA: 1.8%). However, revision rates were significantly higher in the CA group (CA: 10.5% vs. HA: 7.9%; p = .003), with higher numbers of arterial (2.3 vs. 0.9%; p < .001) and venous thromboses (3.4 vs. 1.8%; p = .001) accounting for this finding. CONCLUSIONS: All taken into account, our findings do support the feasibility of venous coupler anastomoses in principle, however the inflationary use of coupler devices should be evaluated critically.

Association Between Use of a Flying Intervention Team vs Patient Interhospital Transfer and Time to Endovascular Thrombectomy Among Patients With Acute Ischemic Stroke in Nonurban Germany.

Importance: The benefit of endovascular thrombectomy (EVT) for acute ischemic stroke is highly time-dependent, and it is challenging to expedite treatment for patients in remote areas. Objective: To determine whether deployment of a flying intervention team, compared with patient interhospital transfer, is associated with a shorter time to endovascular thrombectomy and improved clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This was a nonrandomized controlled intervention study comparing 2 systems of care in alternating weeks. The study was conducted in a nonurban region in Germany including 13 primary telemedicine-assisted stroke centers within a telestroke network. A total of 157 patients with acute ischemic stroke for whom decision to pursue thrombectomy had been made and deployment of flying intervention team or patient interhospital transfer was initiated were enrolled between February 1, 2018, and October 24, 2019. The date of final follow-up was January 31, 2020. Exposures: Deployment of a flying intervention team for EVT in a primary stroke center vs patient interhospital transfer for EVT to a referral center. Main Outcomes and Measures: The primary outcome was time delay from decision to pursue thrombectomy to start of the procedure in minutes. Secondary outcomes included functional outcome after 3 months, determined by the distribution of the modified Rankin Scale score (a disability score ranging from 0 [no deficit] to 6 [death]). Results: Among the 157 patients included (median [IQR] age, 75 [66-80] y; 80 [51%] women), 72 received flying team care and 85 were transferred. EVT was performed in 60 patients (83%) in the flying team group vs 57 (67%) in the transfer group. Median (IQR) time from decision to pursue EVT to start of the procedure was 58 (51-71) minutes in the flying team group and 148 (124-177) minutes in the transfer group (difference, 90 minutes [95% CI, 75-103]; P < .001). There was no significant difference in modified Rankin Scale score after 3 months between patients in the flying team (n = 59) and transfer (n = 57) groups who received EVT (median [IQR] score, 3 [2-6] vs 3 [2-5]; adjusted common odds ratio for less disability, 1.91 [95% CI, 0.96-3.88]; P = .07). Conclusions and Relevance: In a nonurban stroke network in Germany, deployment of a flying intervention team to local stroke centers, compared with patient interhospital transfer to referral centers, was significantly associated with shorter time to EVT for patients with acute ischemic stroke. The findings may support consideration of a flying intervention team for some stroke systems of care, although further research is needed to confirm long-term clinical outcomes and to understand applicability to other geographic settings.

Medial Open Wedge High tibial Osteotomy (MOWHTO) does not relevantly alter patellar kinematics: a cadaveric study.

PURPOSE: The purpose of this study was to quantify the influence of medial open wedge high tibial osteotomy on patellar kinematics using optical computer navigation, as anterior knee pain infrequently occurs postoperatively and the reason is still being unknown. METHODS: Ten medial open wedge high tibial osteotomies at supratuberosity level in 5 full body specimens were performed. The effect of the surgical procedure on patellar kinematics, measured at 5 and 10 degrees of leg alignment correction angle, was analyzed and compared to native patellar kinematics during passive motion-regarding patella shift, tilt, epicondylar distance and rotation. Linear mixed models were used for statistical analysis, a two-sided p value of ≤ 0.05 was considered statistically significant. RESULTS: Tilt behavior, medial shift and epicondylar distance did not show a significant difference regarding natural patellar kinematics at both osteotomy levels. Both osteotomy correction angles showed a significant less external rotation of the patella (p < 0.001, respectively) compared to natural kinematics. CONCLUSIONS: Except less external rotation of the patella, medial open wedge high tibial osteotomy does not seem to relevantly alter patellar alignment during passive motion. Future clinical studies have to prove the effect of MOWHTO on patellar kinematics measured in this experimental setup, especially regarding its influence on anterior knee pain.

Implementing fast-track in total hip arthroplasty: rapid mobilization with low need for pain medication and low pain values : Retrospective analysis of 102 consecutive patients.

INTRODUCTION: Total hip arthroplasty (THA) is reported to be one of the most painful surgical procedures. Perioperative management and rehabilitation patterns are of great importance for the success of the procedure. The aim of this cohort study was the evaluation of function, mobilization and pain scores during the inpatient stay (6 days postoperatively) and 4 weeks after fast-track THA. MATERIALS AND METHODS: A total of 102 consecutive patients were included in this retrospective cohort trial after minimally invasive cementless total hip arthroplasty under spinal anesthesia in a fast-track setup. The extent of mobilization under full-weight-bearing with crutches (walking distance in meters and necessity of nurse aid) and pain values using a numerical rating scale (NRS) were measured. Function was evaluated measuring the range of motion (ROM) and the ability of sitting on a chair, walking and personal hygiene. Furthermore, circumferences of thighs were measured to evaluate the extent of postoperative swelling. The widespread Harris Hip Score (HHS) was used to compare results pre- and 4 weeks postoperatively. RESULTS: Evaluation of pain scores in the postoperative course showed a constant decrease in the first postoperative week (days 1-6 postoperatively). The pain scores before surgery were significantly higher than surgery (day 6), during mobilization (p < 0.001), at rest (p < 0.001) and at night (p < 0.001). All patients were able to mobilize on the day of surgery. In addition, there was a significant improvement in independent activities within the first 6 days postoperatively: sitting on a chair (p < 0.001), walking (p < 0.001) and personal hygiene (p < 0.001). There was no significant difference between the measured preoperative and postoperative (day 6 after surgery) thigh circumferences above the knee joint. Compared to preoperatively, there was a significant (p < 0.001) improvement of the HHS 4 weeks after surgery. In 100% of the cases, the operation was reported to be successful and all of the treated patients would choose a fast-track setup again. CONCLUSION: Application of a fast-track scheme is effective regarding function and mobilization of patients. Low pain values and rapid improvement of walking distance confirms the success of the fast-track concept in the immediate postoperative course. Future prospective studies have to confirm the results comparing a conventional and a fast-track pathway.

Conspicuity of malignant pleural mesothelioma in contrast enhanced MDCT - arterial phase or late phase?

BACKGROUND: To determine if late phase is superior to arterial phase intraindividually regarding conspicuity of MPM in contrast enhanced chest MDCT. METHODS: 28 patients with MPM were included in this retrospective study. For all patients, chest CT in standard arterial phase (scan delay ca. 35 s) and abdominal CT in portal venous phase (scan delay ca. 70 s) was performed. First, subjective analysis of tumor conspicuity was done independently by two radiologists. Second, objective analysis was done by measuring Hounsfield units (HU) in tumor lesions and in the surrounding tissue in identical locations in both phases. Differences of absolute HUs in tumor lesions between phases and differences of contrast (HU in lesion - HU in surrounding tissue) between phases were determined. HU measurements were compared using paired t-test for related samples. Potential confounding effects by different technical and epidemiological parameters between phases were evaluated performing a multiple regression analysis. RESULTS: Subjective analysis: In all 28 patients and for both readers conspicuity of MPM was better on late phase compared to arterial phase. Objective analysis: MPM showed a significantly higher absolute HU in late phase (75.4 vs 56.7 HU, p < 0.001). Contrast to surrounding tissue was also significantly higher in late phase (difference of contrast between phases 18.5 HU, SD 10.6 HU, p < 0.001). Multiple regression analysis revealed contrast phase and tube voltage to be the only significant independent predictors for tumor contrast. CONCLUSIONS: In contrast enhanced chest-MDCT for MPM late phase scanning seems to provide better conspicuity and higher contrast to surrounding tissue compared to standard arterial phase scans.

Brief report: attitudes towards Covid-19 vaccination among hospital employees in a tertiary care university hospital in Germany in December 2020.

Coronavirus disease 2019 (Covid-19) vaccination is essential to fight the pandemic. Health care workers (HCWs) are prioritized to get vaccinated, yet uptake of recommended vaccinations is known to be low in this group. In a tertiary care university hospital with a high number of Covid-19 patients in intensive care, 59.5% of surveyed staff (N = 2454) were willing to get vaccinated, 21.4% were unsure and 18.7% refused. Vaccine hesitancy was higher in female, younger and healthy employees without contact to Covid-19 patients; nurses (53.3%) were much less willing to get vaccinated compared to physicians (82.7%).

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study.

BACKGROUND: During venovenous extracorporeal membrane oxygenation (vvECMO), direct thrombin inhibitors are considered by some potentially advantageous over unfractionated heparin (UFH). We tested the hypothesis that Argatroban is non-inferior to UFH regarding thrombosis and bleeding during vvECMO. METHODS: We conducted a propensity-score matched observational non-inferiority study of consecutive patients without heparin-induced-thrombocytopenia (HIT) on vvECMO, treated between January 2006 and March 2019 in the medical intensive care unit at the University Hospital Regensburg. Anticoagulation was realized with UFH until August 2017 and with Argatroban from September 2017 onwards. Target activated partial thromboplastin time was 50 ± 5seconds in both groups. Primary composite endpoint was major thrombosis and/or major bleeding. Major bleeding was defined as a drop in hemoglobin of ≥ 2 g/dl/day or in transfusion of ≥ 2 packed red cells/24 h, or retroperitoneal, cerebral, or pulmonary bleeding. Major thrombosis was defined as obstruction of > 50% of the vessel lumen diameter by means of duplex sonography. We also assessed technical complications such as oxygenator defects or pump head thrombosis, the time-course of platelets, and the cost of anticoagulation (including HIT-testing). RESULTS: Out of 465 patients receiving UFH, 78 were matched to 39 patients receiving Argatroban. The primary endpoint occurred in 79% of patients in the Argatroban group and in 83% in the UFH group (non-inferiority for Argatroban, p = 0.026). The occurrence of technical complications was equally distributed (Argatroban 49% vs. UFH 42%, p = 0.511). The number of platelets was similar in both groups before ECMO therapy but lower in the UFH group after end of ECMO support (median [IQR]: 141 [104;198]/nl vs. 107 [54;171]/nl, p = 0.010). Anticoagulation costs per day of ECMO were higher in the Argatroban group (€26 [13.8;53.0] vs. €0.9 [0.5;1.5], p < 0.001) but not after accounting for blood products and HIT-testing (€63 [42;171) vs. €40 [17;158], p = 0.074). CONCLUSION: In patients without HIT on vvECMO, Argatroban was non-inferior to UFH regarding bleeding and thrombosis. The occurrence of technical complications was similarly distributed. Argatroban may have less impact on platelet decrease during ECMO, but this finding needs further evaluation. Direct drug costs were higher for Argatroban but comparable to UFH after accounting for HIT-testing and transfusions.

Invasiveness of Treatment Is Gender Dependent in Intensive Care: Results From a Retrospective Analysis of 26,711 Cases.

BACKGROUND: Health care and outcome of critically ill patients are marked by gender-related differences. Several studies have shown that male patients in intensive care units (ICU) more often receive mechanical ventilation, dialysis, pulmonary arterial catheterization (PAC), and central venous catheterization (CVC). We investigated gender-related differences in ICU treatment and mortality. METHODS: This retrospective, single-center study analyzed adult ICU patients admitted to the University Medical Center Regensburg between January 2010 and December 2017. Illness severity was measured with the Simplified Acute Physiology Score II (SAPS II) at ICU admission. We evaluated the intensity of ICU treatment according to the implementation of tracheostomy and extracorporeal membrane oxygenation (ECMO). We then assessed gender-related differences in the duration of mechanical ventilation and other invasive monitoring (PAC) and treatment methods (CVC, endotracheal intubation rate, and dialysis). ICU treatment and mortality data were obtained from an electronic data capture system. After adjusting for age, reason for hospitalization, and SAPS II score, we assessed the influence of gender on the intensity of ICU treatment using multivariable logistic regression. Odds ratios (OR) for the logistic regression models and incidence rate ratios (IRR) for the negative binomial regression models were calculated as effect estimates together with the corresponding 95% confidence intervals (95% CI). A P value of <.05 was considered significant. RESULTS: The study analyzed 26,711 ICU patients (64.8% men). The ICU mortality rate was 8.8%. Illness severity, ICU, and hospital mortality did not differ by gender. Women were older than men (62.6 vs 61.3 years; P < .001) at ICU admission. After multivariable adjustment, men were more likely to undergo tracheostomy (OR = 1.39 [1.26-1.54]), ECMO (OR = 1.37 [1.02-1.83]), dialysis (OR = 1.29 [1.18-1.41]), and PAC insertion (OR = 1.81 [1.40-2.33]) and had a longer duration of mechanical ventilation than women (IRR = 1.07 [1.02-1.12]). The frequency of endotracheal intubation (OR = 1.04 [0.98-1.11]) and placement of CVC (OR = 1.05 [0.98-1.11]) showed no gender-specific differences. Of ICU nonsurvivors, men were more likely to undergo tracheostomy (20.1% vs 15.3%; P = .004) and dialysis (54% vs 46.4%; P < .001) than women and had a longer duration of mechanical ventilation (6.3 vs 5.4 days; P = .015). CONCLUSIONS: After adjustment for severity of disease and outcome, ICU treatment differs between men and women. Men were more likely than women to undergo tracheostomy and ECMO.