MYD88L265P augments proximal B-cell receptor signaling in large B-cell lymphomas via an interaction with DOCK8.

Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous disease with at least 5 recognized molecular subtypes. Cluster 5 (C5)/MCD tumors frequently exhibit concurrent alterations in the toll-like receptor (TLR) and B-cell receptor (BCR) pathway members, MYD88L265P and CD79B, and have a less favorable prognosis. In healthy B cells, the synergy between TLR and BCR signaling pathways integrates innate and adaptive immune responses and augments downstream NF-κB activation. In addition, physiologic TLR9 pathway engagement via MYD88, protein tyrosine kinase 2 (PYK2), and dedicator of cytokinesis 8 (DOCK8) increases proximal BCR signaling in healthy murine B cells. Although C5/MCD DLBCLs are selectively sensitive to Bruton tyrosine kinase (BTK) inhibition in in vitro studies and certain clinical trials, the role of mutated MYD88 in proximal BCR signaling remains undefined. Using engineered DLBCL cell line models, we found that concurrent MYD88L265P and CD79B alterations significantly increased the magnitude and duration of proximal BCR signaling, at the level of spleen tyrosine kinase and BTK, and augmented PYK2-dependent DOCK8 phosphorylation. MYD88L265P DLBCLs have significantly increased colocalization of DOCK8 with both MYD88 and the proximal BCR-associated Src kinase, LYN, in comparison with MYD88WT DLBCLs, implicating DOCK8 in MYD88L265P/proximal BCR cross talk. Additionally, DOCK8 depletion selectively decreased proximal BCR signaling, cellular proliferation, and viability of DLBCLs with endogenous MYD88L265P/CD79BY196F alterations and increased the efficacy of BTK blockade in these lymphomas. Therefore, MYD88L265P/DOCK8-enhanced proximal BCR signaling is a likely mechanism for the increased sensitivity of C5/MCD DLBCLs to BTK blockade.

Retrospective analysis of the perioperative outcome in living donor kidney transplantation with multiple renal arteries: does accessory vessel ligation affect the outcome?

PURPOSE: Accurate surgical reconstruction of arterial vascular supply is a crucial part of living kidney transplantation (LDKT). The presence of multiple renal arteries (MRA) in grafts can be challenging. In the present study, we investigated the impact of ligation versus anastomosis of small accessory graft arteries on the perioperative outcome. METHODS: Clinical and radiological outcomes of 51 patients with MRA out of a total of 308 patients who underwent LDKT with MRA between 2011 and 2020 were stratified in two groups and analyzed. In group 1 (20 patients), ligation of accessory arteries (ARAs) and group 2 (31 patients) anastomosis of ARAs was performed. RESULTS: Significant differences were observed in the anastomosis-, surgery-, and warm ischemia time (WIT) in favor of group 1. Students t-test showed comparable serum creatinine levels of 2.33 (± 1.75) to 1.68 (± 0.83) mg/dL in group 1 and 2.63 (± 2.47) to 1.50 (± 0.41) mg/dL in group 2, were seen from 1 week to 1 year after transplant. No increased rates of Delayed graft function (DGF), primary transplant dysfunction and transplant rejection were seen, but graft loss and revision rates were slightly higher when the ARAs were ligated. Analysis of Doppler sonography revealed that segmental perfusion deficits tend to regenerate during the clinical course. CONCLUSION: Ligation of smaller accessory renal arteries may not affect the outcome of living kidney transplantation, except for a minor increase in the reoperation rate. Segmental perfusion deficits of the graft seem to regenerate in most cases as seen in Doppler sonography.

Transplant nephrectomy: indication, surgical approach and complications-experiences from a single transplantation center.

PURPOSE: Management of a failed kidney allograft, and the question whether it should be removed is a challenging task for clinicians. The reported risks for transplant nephrectomy (TN) vary, and there is no clear recommendation on indications or surgical approach that should be used. This study gives an overview of indications, compares surgical techniques, and identifies risk factors for higher morbidity. METHODS: Retrospective analysis was conducted on all transplant nephrectomies performed between 2005 and 2020 at Charité Hospital Berlin, Department of Urology. Patient demographics, laboratory parameters, graft survival data, indication for TN, and surgical complications were extracted from medical reports. RESULTS: A total of 195 TN were performed, with graft intolerance syndrome being the most common indication in 52 patients (26.7%), acute rejection in 36 (18.5%), acute infection in 30 (15.4%), and other reasons to stop immunosuppression in 26 patients (13.3%). Rare indications were vascular complications in 16 (8.2%) and malignancies in the allograft in six (3.1%) cases. Extracapsular surgical approach was significantly more often used in cases of vascular complications and earlier allograft removal, but there was no difference in complication rates between extra- and intracapsular approach. Acute infection was identified as an independent risk factor for a complication grade IIIb or higher according to Clavien-Dindo classification, with a HR of 12.3 (CI 2.2-67.7; p = 0.004). CONCLUSION: Transplant nephrectomy should only be performed when there is a good indication, and non-elective surgery should be avoided, when possible, as it increases morbidity.

Regional socioeconomic deprivation in Germany and nicotine use among children and adolescents.

To assess the association of regional socioeconomic deprivation and nicotine use, survey data from 17,877 pupils aged 9-17 years were analysed. Lifetime use of combustible, e-cigarettes, and both products were the outcome variables. The German Index of Socioeconomic Deprivation was the exposure variable. Logistic regression models controlling for age, gender, school type, and sensation seeking were used to examine associations between regional socioeconomic deprivation and nicotine use. Ever use of combustible cigarettes was 17.8%, of e-cigarettes 19.6%, and of both products 13.4%. Compared to the most affluent area, the adjusted odds ratio of combustible cigarette use in the most deprived area was 2.24 (95% CI: 1.67-3.00), of e-cigarette use 1.56 (95% CI: 1.20-2.03), and of poly use 1.91 (95% CI: 1.36-2.69). Nicotine use among young people across ages and especially in socioeconomic-deprived areas was widespread. Nicotine control measures are urgently needed to reduce smoking and vaping in German adolescents.

The effects of auditory cues and weighted pens on handwriting in individuals with Parkinson's disease.

BACKGROUND: Micrographia, or small handwriting, is a common symptom of Parkinson's disease (PD). Weighted pens have previously been recommended to improve handwriting, but there is limited research supporting their effectiveness. Additionally, previous research has demonstrated that music as an auditory cue can reduce variability in fine motor movements, but its effect on handwriting in people with PD remains unknown. PURPOSE: This study explored potential handwriting interventions for people with PD by evaluating the effectiveness of weighted pens and auditory cues on handwriting. STUDY DESIGN: This was a pilot cohort study. METHODS: Eight older adults with PD used a standard pen and a weighted pen to write continuous cursive "l"s on 1.5-cm-lined paper for a total of 10 seconds while listening to auditory cues in 4 conditions: control (silence), metronome, activating music, and relaxing music. Kinematic data were measured with sensors attached to the tip of each pen, and muscle activity was measured with electromyography sensors adhered to the extensor digitorum communis and first dorsal interosseous. RESULTS: When writing with the standard pen, peak-to-peak time was reduced in the metronome (control = 0.807 ± 0.121 seconds, metronome = 0.701 ± 0.100 seconds, p = 0.024) and activating (control = 0.807 ± 0.121 seconds, activating = 0.691 ± 0.113 seconds, p = 0.009) conditions compared to the control condition. Furthermore, the weighted pen increased the variability of distance between letter peaks (standard = 0.187 ± 0.010, weighted = 0.482 ± 0.065, p = 0.033) and the variability of time needed to complete each letter (standard = 0.176 ± 0.010, weighted = 0.187 ± 0.016, p = 0.042) compared to the standard pen. Finally, area under the curve of the extensor digitorum communis was reduced in the metronome (metronome = 66.03 ± 25.74 mV, control = 88.98 ± 30.40 mV, p = 0.034) and activating music (activating = 66.49 ± 26.02 mV, control = 88.98 ± 30.40 mV, p = 0.012) conditions compared to control when writing with the standard pen. CONCLUSIONS: These results suggest that weighted pens may not improve handwriting in novice users, but auditory cues appear beneficial. This can inform future directions in the research and clinical application of handwriting interventions for persons with PD.

[Use of tobacco cigarettes, e-cigarettes, and shishas among children and adolescents: Results of the 'Präventionsradar' from 2016 to 2023]. / Konsum von Tabakzigaretten, E-Zigaretten und Wasserpfeifen bei Kindern und Jugendlichen. Ergebnisse des Präventionsradars von 2016 bis 2023.

AIM: To measure trends in the use of various smoking products among children and adolescents from 2016 to 2023. METHOD: The data is based on seven waves of the "Präventionsradar", a school-based epidemiological study in grades 5 to 10. The primary endpoints of the study were the lifetime and monthly prevalence of the use of tobacco cigarettes, e-cigarettes, shisha and the use of at least two of these smoking products (combined use). Prevalence estimates are based on logistic regression models. RESULTS: The analysis was based on 94,127 questionnaires. The sex ratio was balanced (49% female), mean age was 13 years (SD=1.8). In 2022/2023, the lifetime prevalence of smoking tobacco cigarettes was 18.8% (95% CI 18.1-19.5), of e-cigarettes 23.5% (95% CI 22.8-24.3), of shisha 14.0% (95% CI 13.4-14.7) and combined use 19.0% (95% CI 18.3-19.7). The monthly prevalence of smoking tobacco cigarettes was 5.9% (95% CI 5.5-6.4), of e-cigarettes 7.0% (95% CI 6.5-7.4), of shisha 3.2% (95% CI 2.8-3.5) and combined use 4.8% (95% CI 4.4-5.2). The following trends in lifetime prevalence have emerged since 2016: tobacco cigarettes (-3.0 percentage points), e-cigarettes (+1.8 percentage points), shisha (-9.2 percentage points), combined use (-2.7 percentage points). In the years of the COVID-19 pandemic, youth smoking decreased and rose again post-COVID with the exception of shisha. DISCUSSION: The use of smoking products in adolescence occurs frequently. Over the observational period, a trend reversal towards e-cigarettes as the most popular product among children and young people is most likely. In addition, the combined use of several smoking products has become a common pattern of consumption. Consistent preventive measures are required in order to achieve the goal of a smoke-free society in 2040.

[Binge drinking in early adolescence : Results of the "Präventionsradar" from 2016 to 2023]. / Rauschtrinken in der frühen Adoleszenz : Ergebnisse des Präventionsradars von 2016 bis 2023.

INTRODUCTION: In Germany, no other psychotropic substance is consumed as often and in such large quantities during adolescence as alcohol. This work aims to examine trends in binge drinking in early adolescence from 2016 to 2023. METHOD: Based on seven waves of the "Präventionsradar," which is a school-based epidemiological study in lower secondary education, the lifetime as well as the 30-day prevalence of binge drinking (for girls 4, for boys 5 alcoholic drinks on one occasion) were determined for the period from 2016 to 2023 for 12- to 15-year-olds. RESULTS: The analyses were based on 44,713 questionnaires. The sex ratio was balanced (50% female), and the mean age was 13.8 years (SD = 1.02). From 2016 to 2023, lifetime prevalence of binge drinking increased significantly by 3.6 percentage points to 25.3% (95% confidence interval 24.1-26.5). The 30-day prevalence did not change statistically during the observation period and was 15.9% (95% CI 14.9-16.9) in 2023. Compared to the previous year, both lifetime prevalence (-2.5 percentage points) and 30-day prevalence of binge drinking (-3.5 percentage points) decreased significantly in the first year of the COVID-19 pandemic (2020/2021) and increased again in subsequent years. Systematic differences between the genders could not be found. DISCUSSION: The German Youth Protection Act does not allow legal access to alcohol for the age group under study. Against this background, it is worrying that every fourth adolescent already reports experiences of binge drinking. Consistent structural and behavioral prevention measures are necessary to curb the high prevalence of binge drinking in childhood and adolescence.

[Use of tobacco cigarettes, e-cigarettes, and shishas among children and adolescents: Results of the 'Präventionsradar' from 2016 to 2023]. / Konsum von Tabakzigaretten, E-Zigaretten und Wasserpfeifen bei Kindern und Jugendlichen. Ergebnisse des Präventionsradars von 2016 bis 2023.

AIM: To measure trends in the use of various smoking products among children and adolescents from 2016 to 2023. METHOD: The data is based on seven waves of the "Präventionsradar", a school-based epidemiological study in grades 5 to 10. The primary endpoints of the study were the lifetime and monthly prevalence of the use of tobacco cigarettes, e-cigarettes, shisha and the use of at least two of these smoking products (combined use). Prevalence estimates are based on logistic regression models. RESULTS: The analysis was based on 94,127 questionnaires. The sex ratio was balanced (49% female), mean age was 13 years (SD=1.8). In 2022/2023, the lifetime prevalence of smoking tobacco cigarettes was 18.8% (95% CI 18.1-19.5), of e-cigarettes 23.5% (95% CI 22.8-24.3), of shisha 14.0% (95% CI 13.4-14.7) and combined use 19.0% (95% CI 18.3-19.7). The monthly prevalence of smoking tobacco cigarettes was 5.9% (95% CI 5.5-6.4), of e-cigarettes 7.0% (95% CI 6.5-7.4), of shisha 3.2% (95% CI 2.8-3.5) and combined use 4.8% (95% CI 4.4-5.2). The following trends in lifetime prevalence have emerged since 2016: tobacco cigarettes (-3.0 percentage points), e-cigarettes (+1.8 percentage points), shisha (-9.2 percentage points), combined use (-2.7 percentage points). In the years of the COVID-19 pandemic, youth smoking decreased and rose again post-COVID with the exception of shisha. DISCUSSION: The use of smoking products in adolescence occurs frequently. Over the observational period, a trend reversal towards e-cigarettes as the most popular product among children and young people is most likely. In addition, the combined use of several smoking products has become a common pattern of consumption. Consistent preventive measures are required in order to achieve the goal of a smoke-free society in 2040.

Teachers' emotional exhaustion during the COVID-19 pandemic: Levels, changes, and relations to pandemic-specific demands.

We aimed to identify the levels of and changes in emotional exhaustion experienced by teachers and principals during the COVID-19 pandemic and pandemic-related stressors and resources. In a German sample of 2157 teachers and 374 principals, we found high levels and an increase of emotional exhaustion. Results from multi-group structural equation modeling analyses indicated that health concerns and workload were positively and social support negatively related to emotional exhaustion. Additional analyses of an open response question confirmed that teachers and principals experienced their work during the COVID-19 pandemic as predominantly stressful. These results indicate the importance of supporting both teachers and principals in reducing their exhaustion to help students overcome the consequences of the COVID-19 pandemic.

Physical activity, screen time, and sleep: do German children and adolescents meet the movement guidelines?

The interactions between physical activity (PA), screen time, and sleep affect the health of children and adolescents. This study described the national prevalence estimates of German youth aged 9 to 18 years who meet PA, screen time, and sleep guidelines alone and in combination and examined the associations of demographic and personal characteristics with adherence to guidelines. Data from a 2019-2020 German student survey were used (n = 15,786). The target population consisted of children and adolescents enrolled in grades 5-10, with a mean age of 13.0 years (SD = 1.8) and an equal gender distribution (male: 50%). The levels of PA, screen time, and sleep were assessed by self-reports (online questionnaires). The prevalence rates of meeting each guideline individually and in different combinations were calculated, and multilevel logistic regression models were used to examine the associations of demographic and personal characteristics with meeting versus not meeting guidelines. Overall, 9.7% of the respondents met all three guidelines combined, and approximately 25% did not meet any of the guidelines. Half of the participants (50%) met the sleep guidelines, and approximately one third met the screen time (35%) and PA (37%) guidelines alone. Demographic characteristics associated with adherence to meeting all three movement guidelines included younger age, male gender, higher self-reported socioeconomic status, and school type. Personal characteristics related to adherence to meeting all three movement guidelines included better subjective school performance, less frequent attention deficit hyperactivity disorder (ADHD), lower levels of depressive symptoms, lower body mass index (BMI), and not using substances in the past 30 days. CONCLUSION: A low percentage of German children and adolescents met the movement guidelines. With increasing age, the proportion of young people who follow the recommendations decreases. There is an urgent need for health interventions devoted to youth behavior as a whole. WHAT IS KNOWN: • High levels of PA, low levels of screen time, and optimal sleep duration provide enhanced health benefits in comparison to the adoption of just one of these behaviors. • Evidence shows that movement behaviors interact throughout the day and should be studied concurrently. WHAT IS NEW: • Approximately 10% of German children and adolescents met the recommendations on PA, screen time, and sleep, while 25% did not meet any guidelines. • Meeting all guidelines was associated with less frequent ADHD and depressive symptoms, lower BMI, and less frequent substance use in the past 30 days.

[Emotional exhaustion and job satisfaction among teaching staff during the COVID-19 pandemic]. / Emotionale Erschöpfung und Berufszufriedenheit von Lehrpersonal während der COVID-19-Pandemie.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic has significantly changed the everyday professional life of teaching staff. The purpose of this paper is to examine the effects of the pandemic on teachers' emotional exhaustion and job satisfaction. METHODS: A sample of 2531 school administrators and teachers from North Rhine-Westphalia was recruited in October 2020. Changes in emotional exhaustion during the pandemic were directly measured with nine items of the Maslach Burnout Inventory and changes in job satisfaction with six items. Adjusted regression models were used to determine risk and protective factors associated with changes in emotional exhaustion and job satisfaction. RESULTS: Risk factors associated with both more frequently perceived symptoms of exhaustion and reduced job satisfaction were as follows: the additional workload during the pandemic, the stress of uncertainty, the perceived change in workload, concerns about the students, and being employed at an elementary school. A supportive school environment was associated with both fewer perceived symptoms of exhaustion and stable job satisfaction. DISCUSSION: From the perspective of the teaching staff, the COVID-19 pandemic was related to subjective changes in emotional exhaustion and job satisfaction. The COVID-19 pandemic was associated with higher emotional exhaustion for more than half of the teaching staff and with reduced job satisfaction for one in five teachers. Due to the study design, causal conclusions are not possible.

Association between bullying victimization and e-cigarette use among German students.

This study examined the association between bullying victimization and e-cigarette use. Data from a 2019-2020 German student survey were used (N = 16,476). The target population consisted of students enrolled in grades 5-10, with a mean age of 13.1 years (SD = 1.8), and equal gender distribution (49.5% female). Mixed-effect multivariable logistic regression models were used to examine the association between bullying victimization (attacked physically, assaulted verbally, experienced relational bullying, sexual harassment, cyberbullying) and current e-cigarette use. The multivariable analysis controlled for age, sex, sensation-seeking, socioeconomic status, school performance, type of school attended, and substance use (current cigarette smoking, hookah smoking, and alcohol drinking). Overall 510 (3.7%) students reported current use of e-cigarettes. The odds for using e-cigarettes increased each step of being bullied from "never," "rarely," "sometimes," "once a week," to "several times a week" by 2.03 (95% confidence interval [CI]: 1.81, 2.29) in the unadjusted model, and by 1.46 (95% CI: 1.24, 1.71) in the covariate-adjusted model. Data indicate an empirical association between victimization and e-cigarette use among German students. Design limitations prevent the conclusion of a causal relationship, calling for well-designed longitudinal studies to investigate the temporal sequence between victimization and e-cigarette use.

[Alcohol use before the age of 14: marker variable or independent risk factor?] / Alkoholkonsum vor dem 14. Lebensjahr: Markiervariable oder unabhängiger Risikofaktor?

BACKGROUND: Even if the legal age for alcoholic beverages in Germany is 16 or 18, the majority of young people have tried alcohol before this age. Parents are a frequent source of supply, especially for small amounts of alcohol ("sipping"). AIM OF THE WORK: To investigate whether trying small amounts of alcohol is an independent predictor for binge drinking initiation. MATERIAL AND METHODS: A longitudinal analysis was carried out with 2566 students from 6th to 8th grade from thirteen German federal states (survey period 2018 to 2020). Inclusion criteria were an age of 13 years or younger and had never drunk a full drink of alcohol. The main study parameter was the first binge drinking event within 12 months. RESULTS: Of the respondents, 35.9% stated that they had already tried alcohol but had not yet drunk a whole drink, while 64.1% had not yet had any experience with alcohol. After 12 months, those who had tried alcohol stated more often that they had already practiced binge drinking. This relationship persisted even after all study variables associated with binge drinking were controlled including age, type of school, sensation seeking, smoking, consumption of energy drinks and coffee, media time, sleep duration, hyperactivity, and behavior problems (adjusted odds ratio = 2.33; 95% CI 1.64-3.31). DISCUSSION: There was an independent association between prematurely trying alcohol and the onset of binge drinking. The findings are in line with those of other studies that question the practice of early alcohol exposure. However, further studies are necessary to establish a causal relationship.

Energy drink consumption among German adolescents: Prevalence, correlates, and predictors of initiation.

BACKGROUND: Energy drinks (EDs) have become popular worldwide. Despite growing concerns about negative health effects of ED, they are increasingly popular among adolescents, yet little is known about the context and patterns of ED use in adolescents. OBJECTIVE: This study examined the prevalence and correlates of ED use as well as initiation rates and predictors among German adolescents over a one-year period. DESIGN: A school-based longitudinal study of 6902 adolescents ages 9-19 years was conducted in 44 schools in six Federal states of Germany in 2016-2018. Demographics, ED use, drug use behavior, advertising exposure, intrapersonal, interpersonal, and community factors were assessed. RESULTS: Lifetime ED use was reported by 61.7% of the participants, while 21.4% reported past 30-day use. In two multilevel models, lifetime and past 30-day ED use were positively associated with male sex, older age, drug use, poor dietary habits, higher BMI, sensation seeking, worse school performance, and more frequent ad exposure (p < .01). One quarter of the non-users initiated ED use in 12 months. ED initiation was positively associated with male sex (AOR, 1.50 [95% CI, 1.11-2.03]), greater sensation seeking traits (AOR, 1.25 [95% CI, 1.08-1.43]), more frequent ED ad exposure (AOR, 1.31 [95% CI, 1.12-1.53]), and curiosity about trying EDs (AOR, 2.31 [95% CI, 1.74-3.07]), while inversely associated with better school performance (AOR, 0.84, [95% CI, 0.73-0.97]) and attending a gymnasium-type school (AOR, 0.69 [95% CI, 0.50-0.96]). CONCLUSIONS: ED consumption is common among German adolescents. The association between EDs and negative health and lifestyle outcomes and risky behaviors is concerning. Parents, school officials, and healthcare providers should be aware of signs and consequences of excessive ED consumption and limit their use by adolescents. Adopting policies that limit the direct marketing to minors under the age of 18 years can be also beneficial in curbing this epidemic.

Surgical Complications Following Renal Transplantation in a Large Institutional Cohort.

Background: Successful renal transplantation (RTx) relies on immunosuppression and an optimal surgical course with few surgical complications. Studies reporting the postoperative complications after RTx are heterogeneous and often lack systematic reporting of complications. This study aims to describe and identify postoperative short-term and long-term complications after RTx in a large institutional cohort and identify risk factors for a complicated surgical course. Methods: The study is a retrospective single-center cohort of 571 recipients who underwent living or deceased donor open RTx between 2014 and 2021. Data were collected on background information and perioperative and postoperative data. Complications were defined as short-term (<30 d) or long-term (>30 d) after transplantation and graded according to the Clavien-Dindo classification. Multivariable logistic regression was performed to evaluate risk factors for serious short-term complications and multivariable time-dependent Cox regression to evaluate risk factors for long-term complications. Results: A total of 351 patients received a graft from a deceased donor, and 144 of these grafts were on perfusion machine before transplantation. One or more short-term complications occurred in 345 (60%) patients. Previous RTx was associated with short-term Clavien-Dindo >2 complications in recipients (odds ratio = 2.08; 95% confidence interval [CI], 1.18-3.69; P = 0.01). Being underweight (body mass index <18.5) in combination with increasing age increased the odds of short-term Clavien-Dindo >2 and vascular complications. Increasing blood loss per 100 mL was associated with increased odds of short-term Clavien-Dindo >2 (odds ratio = 1.11; 95% CI, 1.01-1.21; P = 0.032). No associations were found for long-term complications after RTx. The 5-y cumulative incidence of graft loss was 12.6% (95% CI, 8.9-16.3). Conclusions: Short-term complications are common after RTx, and risk factors for severe short-term complications include previous RTx, increasing age, and low body mass index. No risk factors were identified for severe long-term complications. Further studies should explore whether new surgical techniques can reduce surgical complications in RTx.

Skills transfer from the DaVinci® system to the Hugo™ RAS system.

PURPOSE: Recently, the robotic surgical system, Hugo™ was approved for clinical use. The transfer of skills is important for understanding the implementation of surgical innovation. We explored the transfer of skills from the DaVinci® to the Hugo™ by studying the learning curve and short-term patient outcomes during radical prostatectomy (RARP). METHODS: We examined the transfer of skills from one surgeon performing RARP from the first case with the Hugo™ system in April 2022. The surgeon had previously performed > 1000 RARPs using DaVinci®. Perioperative and clinical outcomes were collected for procedures on both Hugo™ and DaVinci®. Patient follow-up time was 3 months. RESULTS: Nineteen Hugo™ cases and 11 DaVinci® cases were recorded. No clinically relevant difference in procedure time was found when transferring to Hugo™. Patients operated using Hugo™ had more contacts postoperatively compared to the DaVinci®, all Clavien-Dindo (CD) grade 1 (53% vs 18%). Three patients from the Hugo™ group were re-admitted within 30 days with catheter malfunction (CD grade 1), infection without a focus (CD grade 2), and ileus due to a hernia in the port hole (CD grade 3b). The 3-month follow-up showed similar results in prostate-specific antigen levels (PSA) and erectile dysfunction between the two robotic systems, but a higher incidence of incontinence was found for the Hugo™. CONCLUSION: We observed that the skills of an experienced robotic surgeon are transferable from DaVinci® to Hugo™ when performing RARP. No obvious benefits were found for using Hugo™ compared to DaVinci® for RARP although this needs confirmatory studies.

How experienced robotic nurses adapt to the Hugo™ RAS system.

No studies have reported on the impact at team level of the Medtronic Hugo™ RAS system. We described the work patterns and learning curves of an experienced robotic nurse team adapting to the new robotic system. We prospectively recorded the robotic nurse team's preoperative, perioperative, and postoperative tasks on the first 30 robotic procedures performed. The data were descriptively analyzed, and Gantt Charts were created for a timeline overview of the work patterns. We compared the operative times between the Medtronic Hugo™ RAS and the Davinci® system. The preoperative phase seemed to improve with a median time of 94 min (IQR 81-107). After 20 surgeries, the work pattern became more consistent where the scrub and circulating nurses worked simultaneously. There was no noticeable improvement for the perioperative and postoperative phases with a stable median time of 170 min (IQR 135-189) and 26 min (IQR 22-31). We found that the work pattern seemed to stabilize after 20 surgeries but with a continued decrease in preoperative time without a learning curve plateau. The robotic nurse team suffered from few breaks and long working hours because only a few nurses at our facility were trained in the Hugo™ system.

An inducible Cd79b mutation confers ibrutinib sensitivity in mouse models of Myd88-driven diffuse large B-cell lymphoma.

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma and constitutes a highly heterogenous disease. Recent comprehensive genomic profiling revealed the identity of numerous molecularly defined DLBCL subtypes, including a cluster which is characterized by recurrent aberrations in MYD88, CD79B, and BCL2, as well as various lesions promoting a block in plasma cell differentiation, including PRDM1, TBL1XR1, and SPIB. Here, we generated a series of autochthonous mouse models to mimic this DLBCL cluster and specifically focused on the impact of Cd79b mutations in this setting. We show that canonical Cd79b immunoreceptor tyrosine-based activation motif (ITAM) mutations do not accelerate Myd88- and BCL2-driven lymphomagenesis. Cd79b-mutant murine DLBCL were enriched for IgM surface expression, reminiscent of their human counterparts. Moreover, Cd79b-mutant lymphomas displayed a robust formation of cytoplasmic signaling complexes involving MYD88, CD79B, MALT1, and BTK. These complexes were disrupted upon pharmacological BTK inhibition. The BTK inhibitor-mediated disruption of these signaling complexes translated into a selective ibrutinib sensitivity of lymphomas harboring combined Cd79b and Myd88 mutations. Altogether, this in-depth cross-species comparison provides a framework for the development of molecularly targeted therapeutic intervention strategies in DLBCL.