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1.
Transplant Direct ; 10(6): e1626, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38757053

RESUMEN

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.

2.
World J Urol ; 42(1): 120, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38446250

RESUMEN

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.


Asunto(s)
Riñón , Nefrectomía , Humanos , Estudios Retrospectivos , Nefrectomía/efectos adversos , Trasplante Homólogo , Supervivencia de Injerto
3.
J Robot Surg ; 18(1): 114, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38466477

RESUMEN

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.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Curva de Aprendizaje , Tempo Operativo
4.
Artículo en Alemán | MEDLINE | ID: mdl-38502361

RESUMEN

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.


Asunto(s)
Consumo Excesivo de Bebidas Alcohólicas , Masculino , Humanos , Adolescente , Femenino , Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Pandemias , Alemania/epidemiología , Etanol , Encuestas y Cuestionarios , Consumo de Bebidas Alcohólicas/epidemiología
5.
World J Urol ; 42(1): 161, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38488940

RESUMEN

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.


Asunto(s)
Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Arteria Renal/cirugía , Donadores Vivos , Estudios Retrospectivos , Supervivencia de Injerto , Riñón/diagnóstico por imagen , Riñón/cirugía , Riñón/irrigación sanguínea , Resultado del Tratamiento
7.
Laryngorhinootologie ; 2024 Feb 26.
Artículo en Alemán | MEDLINE | ID: mdl-38408484

RESUMEN

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.

8.
Blood Adv ; 8(5): 1063-1074, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38060829

RESUMEN

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.


Asunto(s)
Adenina , Linfoma de Células B Grandes Difuso , Factor 88 de Diferenciación Mieloide , Piperidinas , Animales , Ratones , Adenina/análogos & derivados , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Mutación , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética
9.
J Hand Ther ; 37(1): 144-152, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37778882

RESUMEN

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.


Asunto(s)
Música , Enfermedad de Parkinson , Humanos , Anciano , Señales (Psicología) , Proyectos Piloto , Escritura Manual
10.
Int J Environ Health Res ; 34(2): 1023-1033, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36966513

RESUMEN

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.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Nicotina , Niño , Humanos , Adolescente , Fumar , Alemania/epidemiología , Factores Socioeconómicos
11.
Int Urol Nephrol ; 56(2): 389-397, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37773578

RESUMEN

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.


Asunto(s)
Disfunción Eréctil , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Masculino , Humanos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/complicaciones , Próstata/cirugía , Prostatectomía/métodos , Disfunción Eréctil/etiología
12.
bioRxiv ; 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38076785

RESUMEN

With age, people tend to accumulate body fat and reduce energy expenditure 1 . Brown (BAT) and beige adipose tissue dissipate heat and increase energy expenditure via the activity of the uncoupling protein UCP1 and other thermogenic futile cycles 2,3 . The activity of brown and beige depots inversely correlates with BMI and age 4-11 , suggesting that promoting thermogenesis may be an effective approach for combating age-related metabolic disease 12-15 . Heme is an enzyme cofactor and signaling molecule that we recently showed to regulate BAT function 16 . Here, we show that heme biosynthesis is the primary contributor to intracellular heme levels in brown adipocytes. Inhibition of heme biosynthesis leads to mitochondrial dysfunction and reduction in UCP1. Although supplementing heme can restore mitochondrial function in heme-synthesis-deficient cells, the downregulation of UCP1 persists due to the accumulation of the heme precursors, particularly propionyl-CoA, which is a product of branched-chain amino acids (BCAA) catabolism. Cold exposure promotes BCAA uptake in BAT, and defects in BCAA catabolism in this tissue hinder thermogenesis 17 . However, BCAAs' contribution to the TCA cycle in BAT and WAT never exceeds 2% of total TCA flux 18 . Our work offers a way to integrate current literature by describing heme biosynthesis as an important metabolic sink for BCAAs.

13.
Front Immunol ; 14: 1313371, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38124747

RESUMEN

Diffuse large B cell lymphoma (DLBCL) is a genetically highly heterogeneous disease. Yet, to date, the vast majority of patients receive standardized frontline chemo-immune-therapy consisting of an anthracycline backbone. Using these regimens, approximately 65% of patients can be cured, whereas the remaining 35% of patients will face relapsed or refractory disease, which, even in the era of CAR-T cells, is difficult to treat. To systematically tackle this high medical need, it is important to design, generate and deploy suitable in vivo model systems that capture disease biology, heterogeneity and drug response. Recently published, large comprehensive genomic characterization studies, which defined molecular sub-groups of DLBCL, provide an ideal framework for the generation of autochthonous mouse models, as well as an ideal benchmark for cell line-derived or patient-derived mouse models of DLBCL. Here we discuss the current state of the art in the field of mouse modelling of human DLBCL, with a particular focus on disease biology and genetically defined molecular vulnerabilities, as well as potential targeting strategies.


Asunto(s)
Modelos Animales de Enfermedad , Linfoma de Células B Grandes Difuso , Animales , Humanos , Ratones , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/tratamiento farmacológico
14.
Pneumologie ; 77(12): 1001-1008, 2023 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-37758039

RESUMEN

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.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Pipas de Agua , Productos de Tabaco , Niño , Humanos , Adolescente , Femenino , Masculino , Pandemias , Encuestas y Cuestionarios , Prevalencia
16.
Children (Basel) ; 10(8)2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37628391

RESUMEN

To examine the relationship between regional socioeconomic deprivation and adherence to the 24-h movement guidelines among children and adolescents, a cross-sectional study was conducted. A total of 17,433 students aged 9-17 participated in a survey in winter 2021/2022. Daily screen time (ST), moderate-to-vigorous physical activity (MVPA), and sleep behavior were outcome variables. The German Index of Socioeconomic Deprivation (GISD), a regional socioeconomic objective measure, was the exposure variable. Associations between GISD and health behaviors were examined using regression models. Models were adjusted for age, gender, school type, and individual self-reported socioeconomic status (SES). The proportions of meeting the MVPA, ST, and sleep duration guidelines were 14%, 22%, and 34%, respectively. A total of 2.3% met all guidelines. Students from the most deprived communities were half as likely to meet all three guidelines compared to students from the most affluent regions (OR = 0.49 [0.28; -0.03], p = 0.010). There was a consistent relationship between GISD and lower levels of adherence to screen time guidelines (most deprived compared to most affluent: OR = 0.49 [0.38; 0.64], p < 0.001). There was no association between GISD and adherence to sleep time guidelines. We found mixed results for the association between GISD and MVPA. Regional SES appears to be an important factor associated with screen time. Screen time should be limited through intervention programs, especially in disadvantaged areas. Parents should be made aware of their children's increased media consumption. Recommendations for screen time should be clearly communicated, as should the health disadvantages of increased media consumption in childhood and adolescence.

17.
Blood ; 142(14): 1219-1232, 2023 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-37467575

RESUMEN

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.


Asunto(s)
Linfoma de Células B Grandes Difuso , Factor 88 de Diferenciación Mieloide , Animales , Humanos , Ratones , Quinasa 2 de Adhesión Focal/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Linfoma de Células B Grandes Difuso/patología , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Receptores de Antígenos de Linfocitos B/metabolismo , Transducción de Señal , Receptores Toll-Like
18.
J Occup Environ Med ; 65(10): e636-e639, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37488773

RESUMEN

OBJECTIVE: In response to elevated risk factors, an opioid hazard awareness training for the sand, stone, and gravel mining sector was developed and embedded in annual safety training. METHODS: After positive results from a prior study among Massachusetts workers, a revised training was disseminated across the United States. Two hundred post-training surveys were obtained and compared with results from the Massachusetts cohort. RESULTS: Participants' knowledge about opioid-based medications, confidence in talking to a doctor about opioids and/or to a coworker about their own use of opioids, and ability to refer struggling coworkers to resources improved. Massachusetts respondents had slightly more favorable responses. Both cohorts had strong positive views of the training. CONCLUSIONS: These results highlight the feasibility and effectiveness of opioid hazard prevention training for a high-risk worker population.


Asunto(s)
Mineros , Arena , Humanos , Estados Unidos , Analgésicos Opioides/uso terapéutico , Minería , Massachusetts
19.
Eur Urol Open Sci ; 52: 115-122, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37284043

RESUMEN

Background: Recurrent urinary tract infections (rUTIs) are common after renal transplantation (RTx), and the impact on graft and patient survival remains controversial. Objective: In this study, we investigate the incidence and risk factors for rUTIs in a cohort of RTx recipients and evaluate the effect on graft and patient survival. Design setting and participants: A retrospective cohort of adult patients who underwent RTx at Rigshospitalet, Denmark, between 2014 and 2021 was evaluated in this study. Outcome measurements and statistical analysis: Risk factors for rUTIs were explored with a multivariable cause-specific Cox proportional hazard analysis. The Kaplan-Meier estimate was used to assess overall survival. Results and limitations: A total of 571 RTx recipients were included. The median age was 52 yr (interquartile range: 42-62 yr). Of the cases, 62% were deceased donor RTx. A total of 103 recipients experienced rUTIs. We found increasing age (hazard ratio [HR]: 1.02 per year increase, 95% confidence interval [95% CI]: 1.00-1.04, p = 0.02), female gender (HR: 2.1, 95% CI: 1.4-3.3, p < 0.001), history of lower urinary tract symptoms (HR: 2.3, 95% CI: 1.4-3.5, p = 0.001), and a UTI within 30 d of surgery (HR: 3.5, 95% CI: 2.1-5.9, p < 0.001) were associated with rUTIs. No influence of rUTIs on overall or graft survival was observed. Conclusions: One in six patients experience rUTIs after RTx. Pre- and postoperative variables affect the risk of rUTIs, but none are easily modifiable. In this cohort, rUTIs did not affect the graft function or survival. The etiology of rUTIs remains poorly understood, and there is a continuous need to study how rUTIs can be reduced and treated optimally. Patient summary: In this study, we looked at the risk factors for recurrent urinary tract infections in patients after kidney transplantation. We conclude that 21.5% of patients experience recurrent urinary tract infections 5 years after kidney transplantation. Multiple risk factors were found and should be taken into consideration by clinicians.

20.
Sci Rep ; 13(1): 6111, 2023 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-37059814

RESUMEN

The objective was to examine pandemic-related changes in depression and anxiety symptoms in adolescents and young adults in Germany considering pre-existing depression and anxiety problems. In this cross-sectional study, 11,523 adolescents and young adults aged 14-21 years who perceived an impact of the Coronavirus disease (COVID-19) pandemic on their mental health reported the frequencies of depression and anxiety symptoms retrospectively for different pre-pandemic and pandemic phases. Data were collected using web-based questionnaires between January 5th and February 20th, 2022. Depression and anxiety were assessed with a modified version of the Patient Health Questionnaire (PHQ-4). Scale-fit cut-offs were used to identify pre-existing elevated depression and anxiety scores. Multilevel mixed linear models were conducted to assess changes in depression and anxiety symptoms from 2019 to 2021 and compare for age, gender and pre-pandemic mental health problems. Among young people who were experiencing mental health changes as a result of the pandemic, the frequency of depression and anxiety symptoms increased during the COVID-19 pandemic. This association was moderated by age, gender, and pre-existing elevated depression/anxiety scores. For young people without elevated pre-pandemic depression/anxiety, the scores increased strongly over time, with 61% reporting elevated depression symptoms and 44% reporting elevated anxiety symptoms in 2021. In contrast, self-perceived change was minimal for adolescents and young adults with elevated pre-pandemic depression and anxiety. Among young people whose mental health has been affected by the COVID-19 pandemic, the group without pre-pandemic mental health conditions reported greater deterioration than those with elevated pre-pandemic depression and anxiety scores. Thus, adolescents and young adults without pre-existing depression and anxiety problems who perceived a change in general mental health due to the pandemic reported an alarming increase in symptoms of depression and anxiety during the COVID-19 pandemic period.


Asunto(s)
COVID-19 , Pandemias , Adolescente , Adulto Joven , Femenino , Humanos , Estudios Transversales , Salud Mental , Estudios Retrospectivos , COVID-19/epidemiología , Ansiedad/epidemiología , Trastornos de la Menstruación , Depresión/epidemiología
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