The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.

Exceptional Response of BRAFV600E-Mutated Acinar Cell CUP to BRAF/MEK Inhibition.

Complete remission of BRAF V600E-driven ACC CUP by BRAF/MEK inhibition underscores importance of precision oncology.

Comprehensive genomic analysis reveals molecular heterogeneity in pediatric ALK-positive anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL(ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA-sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (TP53, MDM4), transcription (JUNB), and epigenetic regulators (TET1, KMT2B, KMT2A, KMT2C, KMT2E). Gene expression and methylation profiling consistently subclassified ALK+ ALCLs into two groups characterized by diferential ALK expression levels. The ALK-low group showed enrichment of pathways associated with immune response, cytokine signaling, and a hypermethylated predominant pattern compared to the ALK- high group, which had more frequent copy number changes, and was enriched with pathways associated with cell growth, proliferation, metabolic pathways, and. Taken together, these findings suggest that there is molecular heterogeneity within pediatric ALK+ALCL, predicting distinct biological mechanisms that may provide novel insights into disease pathogenesis and represent prognostic markers.

[Pneumological Rehabilitation in Long COVID - A Comparative Exploratory Longitudinal Study of Long COVID and Asthma/COPD Rehabilitees]. / Pneumologische Rehabilitation im Antragsheilverfahren bei Long COVID.

BACKGROUND: For some COVID-19 patients, symptoms and health impairments persist for an extended period of time (long COVID). Long-term consequences of the disease can lead to permanent limitations in participatory life. In these cases, medical rehabilitation may be useful. Due to the novelty of the disease, little is known about the need for rehabilitation and therapy and the health benefits of specific rehabilitation interventions. METHODS: A multicentre longitudinal observational study was conducted. Persons affected by long COVID (LC) between 18 and 65 years of age undergoing pulmonary rehabilitation were included. An age-matched comparison group (CG) consisted of rehabilitation patients with bronchial asthma and COPD. Written questionnaires were administered at the beginning and end of rehabilitation, as well as six and twelve months after rehabilitation. Outcomes included parameters of subjective health, occupational outcomes, contents of rehabilitation and rehabilitation aftercare. RESULTS: The sample consisted of 305 participants, of whom 172 were classified as LC and 133 as CG. In the total sample, one third of the participants were male and the average age was 53 years. All rehabilitation participants had high health burdens, LC patients had statistically significantly higher impairments in almost all outcomes recorded. At the beginning of rehabilitation, one third of the respondents were on sick leave, more often in LC than in the CG. Twelve months after rehabilitation, both groups achieved significant health improvement, with LC showing greater improvements in most outcomes (interaction effect p<0.01). Despite success in most parameters, LC patients still showed persistent COVID symptoms at twelve months. One year after rehabilitation, 89% returned to work. CONCLUSION: The majority of rehabilitation patients benefit greatly from pulmonary medical rehabilitation in terms of health and occupation. The content of pulmonary rehabilitation seems to be suitable for this indication group; however, there is an indication-specific use of therapy between CG and LC group. As a result, the LC group seems to need more and different therapies.

Stratifying esophago-gastric cancer treatment using a patient-derived organoid-based threshold.

BACKGROUND AND AIMS: This study sought to determine the value of patient-derived organoids (PDOs) from esophago-gastric adenocarcinoma (EGC) for response prediction to neoadjuvant chemotherapy (neoCTx). METHODS: Endoscopic biopsies of patients with locally advanced EGC (n = 120) were taken into culture and PDOs expanded. PDOs' response towards the single substances of the FLOT regimen and the combination treatment were correlated to patients' pathological response using tumor regression grading. A classifier based on FLOT response of PDOs was established in an exploratory cohort (n = 13) and subsequently confirmed in an independent validation cohort (n = 13). RESULTS: EGC PDOs reflected patients' diverse responses to single chemotherapeutics and the combination regimen FLOT. In the exploratory cohort, PDOs response to single 5-FU and FLOT combination treatment correlated with the patients' pathological response (5-FU: Kendall's τ = 0.411, P = 0.001; FLOT: Kendall's τ = 0.694, P = 2.541e-08). For FLOT testing, a high diagnostic precision in receiver operating characteristic (ROC) analysis was reached with an AUCROC of 0.994 (CI 0.980 to 1.000). The discriminative ability of PDO-based FLOT testing allowed the definition of a threshold, which classified in an independent validation cohort FLOT responders from non-responders with high sensitivity (90%), specificity (100%) and accuracy (92%). CONCLUSION: In vitro drug testing of EGC PDOs has a high predictive accuracy in classifying patients' histological response to neoadjuvant FLOT treatment. Taking into account the high rate of successful PDO expansion from biopsies, the definition of a threshold that allows treatment stratification paves the way for an interventional trial exploring PDO-guided treatment of EGC patients.

The IPTA Nashville Consensus Conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: III - Consensus guidelines for Epstein-Barr virus load and other biomarker monitoring.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority.

Cost-effectiveness analysis alongside the inter-B-NHL ritux 2010 trial: rituximab in children and adolescents with B cell non-Hodgkin's lymphoma.

OBJECTIVES: The randomized controlled trial Inter-B-NHL ritux 2010 showed overall survival (OS) benefit and event-free survival (EFS) benefit with the addition of rituximab to standard Lymphomes Malins B (LMB) chemotherapy in children and adolescents with high-risk, mature B cell non-Hodgkin's lymphoma. Our aim was to assess the cost-effectiveness of rituximab-chemotherapy versus chemotherapy alone in the French setting. METHODS: We used a decision-analytic semi-Markov model with four health states and 1-month cycles. Resource use was prospectively collected in the Inter-B-NHL ritux 2010 trial (NCT01516580). Transition probabilities were assessed from patient-level data from the trial (n = 328). In the base case analysis, direct medical costs from the French National Insurance Scheme and life-years (LYs) were computed in both arms over a 3-year time horizon. Incremental net monetary benefit and cost-effectiveness acceptability curve were computed through a probabilistic sensitivity analysis. Deterministic sensitivity analysis and several sensitivity analyses on key assumptions were also conducted, including one exploratory analysis with quality-adjusted life years as the health outcome. RESULTS: OS and EFS benefits shown in the Inter-B-NHL ritux 2010 trial translated into the model by rituximab-chemotherapy being the most effective and also the least expensive strategy over the chemotherapy strategy. The mean difference in LYs between arms was 0.13 [95% CI 0.02; 0.25], and the mean cost difference € - 3 710 [95% CI € - 17,877; € 10,525] in favor of rituximab-chemotherapy group. For a € 50,000 per LY willingness-to-pay threshold, the probability of the rituximab-chemotherapy strategy being cost-effective was 91.1%. All sensitivity analyses confirmed these findings. CONCLUSION: Adding rituximab to LMB chemotherapy in children and adolescents with high-risk mature B-cell non-Hodgkin's lymphoma is highly cost-effective in France. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01516580.

Hypersensitivity to metals in metal-on-metal hip arthroplasty: a prospective study of one hundred and thirty five lymphocyte transformation tests.

BACKGROUND: Metal allergy remains a controversial topic in the orthopaedic community. It is not known if or to what degree metal sensitivity contributes to inflammatory soft tissue failures, unexplained residual pain, or clinical complications after total joint replacement with metal prostheses. METHODS: We investigated the efficacy of the lymphocyte transformation test (LTT) in predicting adverse outcomes in patients after receiving a metal joint replacement. Our study cohort consists of 135 metal-on-metal hip resurfacing arthroplasty cases performed between 2013 and 2015. All study patients had an LTT preoperatively. We retrospectively analyzed clinical outcomes and failures for our cohort. RESULTS: There was no difference in LTT reactivity between men and women. Of the 135 patients tested, 46 (34.1% of cohort) tested positive to at least one of the materials comprising their implant, and 78 patients (57.8%) had at least one reactive score to any component of the LTT. After a minimum follow-up of two years, we did not observe an allergic response to the implant in any patients. There were no failures requiring revision. We observed a 2.2% rate of moderate residual pain; no patients with residual pain tested positive for metal sensitivity. When patients with moderate-high LTT reactivity (30.4% of cohort) were compared to the remainder of the study group, there was no difference in HHS or UCLA activity score. There was no correlation between blood metal ion levels and LTT reactivity. CONCLUSION: We were unable to prove any predictive value of the LTT. We failed to identify hypersensitivity to metals in patients with metal-on-metal hip resurfacing arthroplasty.

Shuttle peptide delivers base editor RNPs to rhesus monkey airway epithelial cells in vivo.

Gene editing strategies for cystic fibrosis are challenged by the complex barrier properties of airway epithelia. We previously reported that the amphiphilic S10 shuttle peptide non-covalently combined with CRISPR-associated (Cas) ribonucleoprotein (RNP) enabled editing of human and mouse airway epithelial cells. Here, we derive the S315 peptide as an improvement over S10 in delivering base editor RNP. Following intratracheal aerosol delivery of Cy5-labeled peptide in rhesus macaques, we confirm delivery throughout the respiratory tract. Subsequently, we target CCR5 with co-administration of ABE8e-Cas9 RNP and S315. We achieve editing efficiencies of up-to 5.3% in rhesus airway epithelia. Moreover, we document persistence of edited epithelia for up to 12 months in mice. Finally, delivery of ABE8e-Cas9 targeting the CFTR R553X mutation restores anion channel function in cultured human airway epithelia. These results demonstrate the therapeutic potential of base editor delivery with S315 to functionally correct the CFTR R553X mutation in respiratory epithelia.

Independent factor structure replication of the SAEBRS teacher and student scales.

The purpose of this study was to independently assess the best-fitting factor models of the Social, Academic, and Emotional Behavior Risk Screener (SAEBRS) student and teacher forms. To do this, we used previously published confirmatory factor analysis procedures (see von der Embse, Iaccarino, et al., 2017) in an attempt to replicate the factor structure. Unidimensional, correlated-factors, higher order, bifactor, and bifactor with correlated residuals models were assessed. The bifactor model yielded the best fit for the student, χ² = 286.58, p < .001, χ²/df = 1.91, RMSEA = .070, CFI = .839, TLI = .796, WRMR = 1.047, and teacher forms, χ² = 502.44, p < .001, χ²/df = 3.78, RMSEA = .095, CFI = .977, TLI = .971, WRMR = 1.193. Nonetheless, the majority of the fit statistics indicated an adequate fit for the student form. The SAEBRS Total Behavior score was found to have the greatest reliability for the student, ω = .77, ωH = .76, and teacher forms, ω = .93, ωH = .86, as well. Model, factor, and item-level indexes indicated mixed support for unidimensionality versus multidimensionality on student and teacher forms. Generally, it is implicated that the SAEBRS overall score was the soundest score for screening risk with the student and teacher forms. However, future investigations could consider a wider variety of methods to test competing factor structures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Long-term clinical outcomes of the Biomet M2a-38: a retrospective review of 335 total hip arthroplasty cases.

BACKGROUND: At the turn of the century, over one-third of total hip arthroplasties comprised metal-on-metal bearings. As this patient population and their implants age, it is crucial to understand associated late failure modes and expected long-term functional outcomes. We report the long-term results of a large metal-on-metal uncemented total hip arthroplasty system with unique design characteristics compared to others that have been reported with high failure rates. METHODS: We retrospectively analyze our prospective clinical database to determine overall implant survivorship and functional outcomes. Further, we compare these results to the clinical outcomes reported in orthopedic registries and in other published studies with similar metal-on-metal total hip arthroplasty cohorts. RESULTS: Implant survivorship at 10 years was 99.1% and continued to 97.6% survivorship at 20 years. Implant survivorship at 20 years did not vary significantly between sexes (Male: 98.3%, Female: 97.2%; log-rank p-value = 0.46). Mean whole blood cobalt levels were 2.6 µg/L in unilateral cases, 5.3 µg/L in bilateral patients, and 3.4 µg/L for the combined cohort. Average blood chromium levels were 1.4 µg/L in unilateral patients, 2.9 µg/L in bilateral patients, and 1.8 µg/L for group combined. We observed a 0.9% rate of failure due trunnion corrosion at a mean of 13.1 years postoperatively (10.6-15.6 years) but had no bearing wear failures. CONCLUSIONS: Our 20-year implant survivorship of 97.6% with the M2a-38 bearing surpassed registry benchmarks for THA. This large-bearing (38 mm), full hemisphere coverage metal-on-metal system had no bearing wear failures, one failure of instability, one failure of fixation, and three trunnion failures, perhaps suggesting an optimum balance between stability of the joint and the trunnion.

Post-transplant lymphoproliferative disease in children, adolescents, and young adults.

Post-transplant lymphoproliferative disease (PTLD) remains a major complication of transplantation. PTLD is a rare entity and very heterogenous making consensus on diagnosis and treatment very challenging. The majority are Epstein-Barr virus (EBV) driven, CD20+ B-cell proliferations. PTLD does occur following hematopoietic stem cell transplant (HSCT), but due to the relative short risk period and efficacy of pre-emptive therapy, PTLD following HSCT will not be discussed in this review. This review will focus on the epidemiology, role of EBV, clinical presentation, diagnosis and evaluation and the current and emerging treatment strategies for pediatric PTLD following solid organ transplantation.

Conservation of the Restricted Expression of Brassicaceae Bsister-Like Genes in Seeds Requires a Transposable Element in Arabidopsis thaliana.

Changes in transcription factor binding sites (TFBSs) can alter the spatiotemporal expression pattern and transcript abundance of genes. Loss and gain of TFBSs were shown to cause shifts in expression patterns in numerous cases. However, we know little about the evolution of extended regulatory sequences incorporating many TFBSs. We compare, across the crucifers (Brassicaceae, cabbage family), the sequences between the translated regions of Arabidopsis Bsister (ABS)-like MADS-box genes (including paralogous GOA-like genes) and the next gene upstream, as an example of family-wide evolution of putative upstream regulatory regions (PURRs). ABS-like genes are essential for integument development of ovules and endothelium formation in seeds of Arabidopsis thaliana. A combination of motif-based gene ontology enrichment and reporter gene analysis using A. thaliana as common trans-regulatory environment allows analysis of selected Brassicaceae Bsister gene PURRs. Comparison of TFBS of transcriptionally active ABS-like genes with those of transcriptionally largely inactive GOA-like genes shows that the number of in silico predicted TFBS) is similar between paralogs, emphasizing the importance of experimental verification for in silico characterization of TFBS activity and analysis of their evolution. Further, our data show highly conserved expression of Brassicaceae ABS-like genes almost exclusively in the chalazal region of ovules. The Arabidopsis-specific insertion of a transposable element (TE) into the ABS PURRs is required for stabilizing this spatially restricted expression, while other Brassicaceae achieve chalaza-specific expression without TE insertion. We hypothesize that the chalaza-specific expression of ABS is regulated by cis-regulatory elements provided by the TE.

Effect of rituximab on immune status in children with mature B-cell non-Hodgkin lymphoma: a prespecified secondary analysis of the Inter-B-NHL Ritux 2010 trial.

BACKGROUND: Survival of children and adolescents with high-risk, mature B-cell non-Hodgkin lymphoma is improved by the addition of rituximab to chemotherapy. The effect of rituximab on immune reconstitution after therapy has not been well described. Herein, we evaluate the immune effects of the addition of rituximab to intensive chemotherapy, a prespecified secondary aim of the Inter-B-NHL Ritux 2010 trial. METHODS: The Inter-B-NHL Ritux 2010 trial was an international, open-label, randomised, phase 3 trial in children (age 6 months to 18 years) with high-risk, mature B-cell non-Hodgkin lymphoma, comparing chemotherapy alone or chemotherapy with rituximab. Measures of immune status were completed at baseline, 1 month from the end of treatment, and 1 year from the start of therapy, and yearly thereafter until normalised. For this secondary analysis, we report on the proportions of patients with low lymphocyte counts and immunoglobulin concentrations at these timepoints with total lymphocyte count, B-cell count, and IgG concentration as the main endpoints. Other endpoints of interest included exposure to immunoglobulin replacement therapy and vaccine serologies. The population assessed for immune endpoints was the eligible per-protocol population with at least one immune parameter at one timepoint. Comparisons of immune status were made between the randomised treatment groups. Safety in the post-therapy period was assessed in the population eligible for the immunity study who were followed up at least 3 months after the end of treatment and without cancer-related events. The Inter-B-NHL Ritux 2010 study was registered with ClinicalTrials.gov, NCT01516580; status completed, with analyses of secondary aims ongoing. FINDINGS: From Dec 19, 2011, to June 13, 2017, 421 patients (344 [82%] boys and 77 [18%] girls; mean age was 8·8 years [SD 4·1]) were enrolled and had immune data at baseline during follow-up, or both. The study population included randomly assigned patients (n=289) and a non-randomised cohort enrolled after the planned interim analysis (n=132). At baseline, 99 (34%) of 290 patients with available data (excluding patients with bone marrow disease with peripheral blast cells) had lymphopenia, and 178 (48%) of 368 had hypogammaglobulinemia. 1 month from the end of therapy, patients who received chemotherapy with rituximab were more likely than those who received chemotherapy alone to have lymphopenia (86 [81%] of 106 vs 53 (60%) of 89, odds ratio [OR] 2·92 [95% CI 1·53-5·57], p=0·0011), B-cell lymphopenia (72 [96%] of 75 vs 36 [64%] of 56, OR 13·33 [3·71-47·84], p<0·0001), and hypogammaglobulinemia (67 [71%] of 95 vs 37 [47%] of 79, OR 2·72 [1·45-5·07], p=0·0017). Differences remained at 1 year for hypogammaglobulinemia only (52 [55%] of 94 vs 16 [25%] of 63, OR 3·64 [1·81-7·31], p=0·0003). Patients in the chemotherapy with rituximab group were more likely than those in the chemotherapy group to receive immunoglobulin replacement (26 [16%] 164 vs nine [7%] of 158, hazard ratio [HR] 2·63 [95% CI 1·23-5·62], p=0·010), mainly due to low immunoglobulin concentration. In the combined treatment groups, including non-randomly assigned patients, the proportion of patients who had loss of protective serologies to a vaccine preventable infection varied from four (9%) of 47 for polio to 21 (42%) of 50 for Streptococcus pneumoniae (pneumococcus). One patient (chemotherapy with rituximab group) had a life-threatening infectious event of polymicrobial bacterial sepsis reported 2 months after the final chemotherapy administration. INTERPRETATION: Children with high-risk mature B-cell non-Hodgkin lymphoma receiving chemotherapy with rituximab were at risk of prolonged hypogammaglobulinemia, although severe infections were rare. Strategies for immunoglobulin replacement and revaccination are needed. FUNDING: Clinical Research Hospital Program of the French Ministry of Health, Cancer Research UK, National Institute for Health Research Clinical Research Network in England, Children's Cancer Foundation Hong Kong, US National Cancer Institute, F Hoffmann-La Roche.

Diagnosis and management of post-transplant lymphoproliferative disease following solid organ transplantation in children, adolescents, and young adults.

Post-transplant Lymphoproliferative Disease (PTLD) remains a major complication of solid organ transplantation (SOT) in pediatric patients. The majority are Epstein-Barr Virus (EBV) driven CD20+ B-cell proliferations responsive to reduction to immunosuppression and anti-CD20 directed immunotherapy. This review focusses on the epidemiology, role of EBV, clinical presentation, current treatment strategies, adoptive immunotherapy and future research in EBV + PTLD in pediatric patients.

Shuttle Peptide Delivers Base Editor RNPs to Rhesus Monkey Airway Epithelial Cells In Vivo.

Gene editing strategies for cystic fibrosis are challenged by the complex barrier properties of airway epithelia. We previously reported that the amphiphilic S10 shuttle peptide non-covalently combined with CRISPR-associated (Cas) ribonucleoprotein (RNP) enabled editing of human and mouse airway epithelial cells. Here, to improve base editor RNP delivery, we optimized S10 to derive the S315 peptide. Following intratracheal aerosol of Cy5-labeled peptide cargo in rhesus macaques, we confirmed delivery throughout the respiratory tract. Subsequently, we targeted CCR5 with co-administration of ABE8e-Cas9 RNP and S315. We achieved editing efficiencies of up to 5.3% in rhesus airway epithelia. Moreover, we documented persistence of edited epithelia for up to 12 months in mice. Finally, delivery of ABE8e-Cas9 targeting the CFTR R553X mutation restored anion channel function in cultured human airway epithelial cells. These results demonstrate the therapeutic potential of base editor delivery with S315 to functionally correct the CFTR R553X mutation in respiratory epithelia.

[Pneumological Rehabilitation in Patients with Long Covid - Health Changes at the End of the Inpatient Rehabilitation Measure]. / Pneumologische Rehabilitation bei Long Covid ­ Gesundheitliche Veränderungen am Ende der stationären Rehabilitationsmaßnahme.

BACKGROUND: Some people suffering from Covid-19 can be affected by persistent symptoms and long-term consequences of the disease (Long Covid) beyond their acute phase. Consequently, this can lead to restrictions in participation. Therefore, the focus is on medical rehabilitation in which Long Covid is treated as a new challenge. METHODS: A prospective, exploratory observational study will be conducted. The written survey of Long Covid rehabilitants takes place at the beginning and end of the pneumological rehabilitation. The aim of the study is to describe the rehabilitation contents and goals, the subjective burdens, the social and occupational participation as well as the health-related changes. Among other factors, disease-specific symptoms, quality of life, participation, psychological impairments, fatigue, and performance were recorded. RESULTS: Long Covid rehabilitants (N=221) participate in the written survey. At the end of rehabilitation, the questionnaire survey indicated significant improvements in almost all outcome parameters with a large effect (p<0.01; ES between 0.76 (anxiety) and 1.30 (fatigue)). All corona symptoms, such as breathlessness on exertion, fatigue or lack of strength improved significantly at the end of rehabilitation. Moreover, the rehabilitants most frequently name the improvement of their health (92%), the increase of their performance (92%) and the improvement of the respiratory muscle strength (78%) as rehabilitation goals. In fact, these goals are achieved by 60 to 70%, significantly fewer rehabilitation patients reach the restoration of their ability to work (32%) or a better ability to concentrate (17%). Respiratory physiotherapy, endurance training and medical training therapy are described as most helpful. At the end of rehabilitation, 76% rated their rehabilitation success as good to excellent based on a single question. CONCLUSION: The first data of the study reveal that Long Covid rehabilitants are exposed to substantial burdens. Through medical rehabilitation, the patients experience medical and social support and experience significant improvements in all recorded health-related outcomes.

[Femoral neck blade cut-in after internal fixation of a trochanteric femoral fracture with a TFNA©]. / "Schenkelhalsklingen-Cut-in" nach Osteosynthese einer pertrochantären Femurfraktur mittels TFNA©.

Following fixation of a trochanteric femoral fracture with a TFNA© and despite correct fracture reduction and fixation, a 96-year-old patient suffered a complete cut-in, i.e. a medialization of the entire femoral neck blade through the nail into the hip joint. Against the background of implant development and current literature, this increasingly frequent type of complication is described and distinguished from other fixation failures such as the cut-out. Attempts to explain this phenomenon as well as research options are presented and a pragmatic approach to avoid this problem is outlined.