Prevalence and Potential Risk Factors for Occupational Low Back Pain Among Male Military Pilots: A Study Based on Questionnaire and Physical Function Assessment

Objectives: Low back pain (LBP) has negative implications for the military's combat effectiveness. This study was conducted to determine the prevalence and risk factors of LBP among pilots through a questionnaire and physical function assessments.Methods: Data on the demographic and occupational characteristics, health habits, physical activity, and musculoskeletal injuries of 217 male pilots (114 fighter, 48 helicopter, and 55 transport pilots) were collected using a self-reported questionnaire and physical function assessments.Results: LBP prevalence was 37.8% in the total cohort and 36.0, 45.8, and 34.5% among fighter, helicopter, and transport pilots, respectively. Multivariate regression analysis revealed that the risk factors significantly associated with LBP were neck pain [odds ratio (OR): 3.559, 95% confidence interval (CI): 1.827–6.934], transversus abdominis activation (OR: 0.346, 95% CI: 0.172–0.698), and hip external rotator strength (OR: 0.001, 95% CI: 0.000–0.563) in the total cohort; neck pain (OR: 3.586, 95% CI: 1.365–9.418), transversus abdominis activation (OR: 0.268, 95% CI: 0.094–0.765), hip external rotator strength (OR: 0.000, 95% CI: 0.000–0.949), and weekly flying hours (OR: 3.889, 95% CI: 1.490–10.149) in fighter pilots; irregular strength training (OR: 0.036, 95% CI: 0.003–0.507) and hip external rotator strength (OR: 0.000, 95% CI: 0.000–0.042) in helicopter pilots; and neck pain (OR: 6.417, 95% CI: 1.424–28.909) in transport pilots.Conclusions: High volume flight schedules and weak core muscle functions have significant negative effects on pilots' back health. LBP is commonly associated with high weekly flying hours, worsening neck pain, transversus abdominis insufficient activation, and reduced hip extensor/rotator strength. Risk factors vary among pilots of different aircraft. Thus, specific core muscle training would be especially important for military pilots.

Hyperglycemia Is Not Associated With Higher Volumetric BMD in a Chinese Health Check-up Cohort

Background and PurposeType 2 diabetes mellitus patients have an increased fracture risk despite having higher areal bone mineral density (aBMD) measured by DXA. This apparent paradox might be explained by the overestimation of BMD by DXA due to the higher fat mass in type 2 diabetes mellitus patients. Volumetric BMD (vBMD) as assessed by quantitative CT (QCT) is not influenced by fat mass. We assessed the association of vBMD and fasting plasma glucose in a large cohort of Chinese subjects and compared the vBMD in healthy and diabetic subjects. In addition, we compared the relation between aBMD, vBMD, glucose and fat mass in a subset of this cohort.Materials and Methods10309 participants from the China Biobank project underwent QCT based on chest low dose CT to compute vBMD of L1 and L2 vertebrae and FPG measurements between 2018 and 2019. Among them, 1037 subjects also had spine DXA scans. Data was analyzed using linear regression models.ResultsIn the total cohort (5889 men and 4420 women, mean age 53 years, range 30-96), there was no significant association between vBMD and FPG after adjustment for age (women: p=0.774; men: p=0.149). 291 women and 606 men fitted the diagnostic criteria of diabetes. Both women and men with diabetes had lower vBMD compared to non-diabetic subjects, but this became non-significant after adjusting for age in the total cohort (women: p=0.817; men: p=0.288) and after propensity score matching based on age (women: p=0.678; men: p=0.135). In the DXA subcohort, aBMD was significantly higher in men with diabetes after adjusting for age and this difference disappeared after further adjusting for total fat area (p=0.064).ConclusionWe did not find any effect of fasting plasma glucose or diabetes on the volumetric BMD measured with QCT after adjustment for age. Therefore, vBMD measured with QCT might be a more reliable measurement to diagnose osteoporosis and assess fracture risk than aBMD measured with DXA in diabetic patients.

Single-dose antibiotic prophylaxis compared with multiple-dose protocol in clean pediatric neurosurgical interventions: a nonrandomized, historically controlled equivalence trial

OBJECTIVE Guidelines recommend antimicrobial prophylaxis (AMP) preoperatively for "clean" spinal and cranial surgeries, while dose and timing remain controversial. The use of multiple-dose AMP for such surgeries is under debate in the pediatric context. In this clinical study, the authors aimed to compare single-dose with multiple-dose prophylactic antibiotic usage in cranial and spinal neurosurgical interventions of pediatric patients. METHODS All neurosurgical patients aged 28 days to 18 years who underwent surgery at a single tertiary center were assessed. Three cohorts (noninstrumented clean spinal, noninstrumented cranial, and instrumented cranial interventions), each of which comprised two 50-patient arms (i.e., single-dose AMP and multiple-dose AMP), were included after propensity score–matched retrospective sampling and power analysis. Records were examined for surgical site infections. Using a previously published meta-analysis as the prior and 80% acceptance of equivalence (margin of OR 0.88–1.13), logistic regression was carried out for the total cohort and each subcohort and adjusted for etiology by consideration of multiple-dose AMP as reference. RESULTS The overall sample included 300 age- and sex-matched patients who were evenly distributed in 3 bi-arm cohorts. There was no statistical intercohort difference based on etiology or type of operation (p < 0.05). Equivalence analysis revealed nondiscriminating results for the total cohort (adjusted OR 0.65, 95% CI 0.27–1.57) and each of the subcohorts (noninstrumented clean spinal, adjusted OR 0.65, 95% CI 0.12–3.44; noninstrumented cranial, adjusted OR 0.52, 95% CI 0.14–2.73; and instrumented cranial, adjusted OR 0.68, 95% CI 0.13–3.31). CONCLUSIONS No significant benefit for multiple-dose compared with single-dose AMPs in any of the pediatric neurosurgery settings could be detected. Since unnecessary antibiotic use should be avoided as much as possible, it seems that usage of single-dose AMP is indicated.

Mortality in Inflammatory Rheumatic Diseases: Lithuanian National Registry Data and Systematic Review

Despite significant improvement in survival, rheumatic diseases (RD) are associated with premature mortality rates comparable to cardiovascular and neoplastic disorders. The aim of our study was to assess mortality, causes of death, and life expectancy in an inflammatory RD retrospective cohort and compare those with the general population as well as with the results of previously published studies in a systematic literature review. Patients with the first-time diagnosis of inflammatory RD during 2012–2019 were identified and cross-checked for their vital status and the date of death. Sex- and age-standardized mortality ratios (SMR) as well as life expectancy for patients with inflammatory RDs were calculated. The results of a systematic literature review were included in meta-standardized mortality ratio calculations. 11,636 patients with newly diagnosed RD were identified. During a total of 43,064.34 person-years of follow-up, 950 death cases occurred. The prevailing causes of death for the total cohort were cardiovascular diseases and neoplasms. The age- and sex-adjusted SMR for the total cohort was calculated to be 1.32 (1.23; 1.40). Patients with rheumatoid arthritis if diagnosed at age 18–19 tend to live for 1.63 years less than the general population, patients with spondyloarthritis—for 2.7 years less, patients with connective tissue diseases—for almost nine years less than the general population. The findings of our study support the hypothesis that patients with RD have a higher risk of mortality and lower life expectancy than the general population.

Effectiveness of Regdanvimab Treatment in High-Risk COVID-19 Patients to Prevent Progression to Severe Disease

ObjectiveTo evaluate clinical effectiveness of regdanvimab, a monoclonal antibody agent for treating coronavirus 2019 (COVID-19).MethodsA retrospective cohort study was conducted at two general hospitals during the study period of December 2020 to May 2021. Mild COVID-19 patients with risk factors for disease progression admitted to the hospitals within seven days of symptom onset were enrolled and followed until discharge or referral. Multivariate analyses for disease progression were conducted in the total and propensity score (PS)-matched cohorts.ResultsA total of 778 mild COVID-19 patients were included and classified as the regdanvimab (n = 234) and supportive care (n = 544) groups. Significantly fewer patients required O2 supplementation via nasal prong in the regdanvimab group (8.1%) than in the supportive care group (18.4%, P &lt; 0.001). The decreased risk for O2 support by regdanvimab treatment was noticed in the multivariate analysis of the total cohort (HR 0.570, 95% CI 0.343–0.946, P = 0.030), but it was not statistically significant in the PS-matched cohort (P = 0.057). Progression to severe disease was also significantly lower in the regdanvimab group (2.1%) than in the supportive care group (9.6%, P &lt; 0.001). The significantly reduced risk for progression to severe disease by regdanvimab treatment was observed in the analysis of both the total cohort (HR 0.262, 95% CI 0.103–0.667, P = 0.005) and PS-matched cohort (HR 0.176, 95% CI 0.060–0.516, P = 0.002). Potential risk factors for progression were investigated in the supportive care group and SpO2 &lt; 97% and CRP elevation &gt;1.5 mg/dL were common risk factors for O2 support and progression to severe disease. Among the patients with any of these factors, regdanvimab treatment was associated with decreased risk for progression to severe disease with slightly lower HR (HR 0.202, 95% CI 0.062–0.657, P = 0.008) than that of the total cohort.ConclusionRegdanvimab treatment was associated with a decreased risk of progression to severe disease.

Comparison of CT Volumetry versus Nuclear Renography for Predicting Remaining Kidney Function After Uninephrectomy in Living Kidney Donors

Computed tomography (CT) and nuclear renography are used to determine kidney procurement in living kidney donors (LKDs). The present study investigated which modality better predicts kidney function after donation. This study included 835 LKDs and they were divided into two subgroups based on whether the left-right dominance of kidney volume was concordant with kidney function (concordant group) or not (discordant group). The predictive value for post-donation kidney function between the two imaging modalities was compared at 1 month, 6 months, and > 1 year in total cohort, concordant, and discordant groups. Split kidney function (SKF) measured by both modalities showed significant correlation with each other at baseline. SKFs of remaining kidney measured using both modalities before donation showed significant correlation with eGFR (estimated glomerular filtration rate) after donation in the total cohort group and two subgroups, respectively. CT volumetry was superior to nuclear renography for predicting post-donation kidney function in the total cohort group and both subgroups. In the discordant subgroup, a higher tendency of kidney function recovery was observed when kidney procurement was determined based on CT volumetry. In conclusion, CT volumetry is preferred when determining procurement strategy especially when discordance is found between the two imaging modalities.

Stroke Aetiology and Collateral Status in Acute Ischemic Stroke Patients Receiving Reperfusion Therapy—A Meta-Analysis

Background: The interplay between collateral status and stroke aetiology may be crucial in the evaluation and management of acute ischemic stroke (AIS). Our understanding of this relationship and its level of association remains sub-optimal. This study sought to examine the association of pre-intervention collateral status with stroke aetiology, specifically large artery atherosclerosis (LAA) and cardio-embolism (CE), in AIS patients receiving reperfusion therapy, by performing a meta-analysis. Methods: Relevant search terms were explored on Medline/PubMed, Embase and Cochrane databases. Studies were included using the following inclusion criteria: (a) patients aged 18 or above; (b) AIS patients; (c) patients receiving reperfusion therapy; (d) total cohort size of >20, and (e) qualitative or quantitative assessment of pre-intervention collateral status on imaging using a grading scale. Random-effects meta-analysis was performed to investigate the association of aetiology with pre-intervention collateral status, and forest plots of risk ratio (RR) were generated. Results: A meta-analysis was conducted on seven studies, with a cumulative cohort of 1235 patients, to assess the association of pre-intervention collateral status with stroke aetiology. Patients with LAA were associated significantly with an increased rate of good collaterals (RR 1.24; 95% CI 1.04–1.50; p = 0.020, z = 2.33). Contrarily, CE aetiology was associated significantly with a decreased rate of good collaterals (RR 0.83; 95% CI 0.71–0.98; p = 0.027, z = −2.213). Conclusions: This study demonstrates that, in AIS patients receiving reperfusion therapy, LAA and CE aetiologies are associated significantly with collateral status.

Efficacy Outcomes of Isatuximab with Pomalidomide and Dexamethasone Are Comparable to (ICARIA-MM) Trial Data: Initial Results of a UK-Wide Real-World Study of Relapsed Myeloma Patients

Objective: Real-world data on the efficacy and tolerability of isatuximab with pomalidomide and dexamethasone (IsaPomDex) in relapsed/refractory myeloma (RRMM) patients are limited. In this UK-wide retrospective study, IsaPomDex outcomes were evaluated across 24 UK cancer centres. Methods: The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events (AEs). Patients were censored at the end of their follow up period, if they did not experience a PFS or OS event. A 3-month landmark analysis was conducted to assess the influence of pomalidomide and dexamethasone dose intensity, and of myeloma response on survival outcomes Results: In a total cohort of 107 patients, median follow up (IQR) was 3.7 months (0.5-12.4 months), median age (IQR) was 69 years (61-77); median (IQR) Charlson Co-morbidity Index (CCI) score was 3 (2-4), 61.7 % had CCI &lt;4 and 80.4% had PS&lt;2. Renal presentation (e-GFR&lt;60 ml/min) in the total cohort was 43%; 28 patients had ISS III staging (from 85 patients with known data), 15 patients had high risk cytogenetics (from 62 patients with known data). Median (range) number of prior therapies was 3 (2-5). Prior therapies included transplant (60.7%), alkylator (99.1%), PI (99.1%), IMiD (100%), anti-CD38 (4.7%) and HDACi (3.7%). Median (IQR) number of IsaPomDex cycles administered was 4 (2-8). ORR in the total cohort was 61.7% with responses categorised as: ≥VGPR: 25.2%, PR: 36.5%, SD: 18.7%, PD: 14% and unknown: 5.6%. Median time (IQR) to objective response (≥PR) was 2.67 months (1.6-4.6). Median PFS in the total cohort was 10.1 months (95% CI: 6.0-12.5). PFS survival probability at 3 months was 82.4% (95% CI: 72.7-88.9). Pomalidomide and dexamethasone doses were reduced in 40.2% and 41.1% of patients, respectively. Treatment is ongoing in 68.2% of patients and was discontinued in 31.8%. Reasons for treatment discontinuation were: death of any cause (14.9%), PD (14.9%) and toxicity (1.9%). Patients in the older subgroup and those with a higher co-morbidity burden achieved statistically insignificant differences in ORR: by age (&lt;75: vs. ≥75 years, p=0.448), and by co-morbidities (CCI &lt;4 vs. ≥ 4, p=0.635). ORR was not statistically lower in the dose-attenuated cohort (full dose vs. Pom OR Dex ↓, Pearson chi2 p=0.322; full dose vs. Pom AND Dex ↓, Pearson chi2 p=0.214). There was no statistical difference in median PFS by age (&lt;65 years: 10.2 vs. 65-74: not reached (NR) vs. ≥75: 7.9 months, log-rank p=0.323), by co-morbidity score (&lt;4: 9.0 months vs. ≥4: NR, log-rank p=0.6339), or by e-GFR renal impairment (≥60: 11.2 vs. &lt;60: 7.9 months, log-rank p=0.1259). The 3-month land-mark analysis, used to reduce the risk of survivorship bias, demonstrated no statistical difference in PFS according to dose intensity of pomalidomide (&lt;4mg vs. 4mg, log-rank p=0.1162) or dexamethasone (&lt;100% vs. 100%, log-rank p=0.2421), but there was a statistically improved PFS in those who achieved ≥PR response (log-rank p= 0.0005). Median OS for the total cohort was not reached (95% CI: 8.4-not estimable). OS survival probability at 3 months was 87.2% (95% CI: 78.5-92.6%) and at 6 months 75.1% (95% CI: 62.9-83.8%). Median OS was not reached for any of the age subgroups (&lt;65: NR vs. 65-74: NR vs. ≥75: NR, log-rank p=0.3422), and for any co-morbidity subgroups (&lt;4: NR vs. ≥4: NR, log-rank p=0.4654). Any grade AEs was experienced by 87.9% of patients. The most common (&gt;10%) any grade AEs were neutropenia (65.4%), thrombocytopenia (23.4%), infections (23.4%), anaemia (15.9%), and fatigue (10.3%). The total number of all ≥G3 AEs was 119; experienced by a total of 67 patients (62.6%). The most common (&gt;10%) ≥G3 AEs were: neutropenia (45.8%), infections (18.7%) and thrombocytopenia (14%). The total number of all ≥G3 haematological AEs was 80; experienced by 57 patients (53.2%). Conclusion: To our knowledge, this is the first study to describe IsaPomDex outcomes in the real-world. It demonstrated encouraging ORR and PFS outcomes in RRMM in the routine care setting, and these were comparable to ICARIA-MM trial data. However, close monitoring and dose adjustments are required to manage toxicities. Longer follow up of patients in this cohort will enable a further assessment of these initial outcomes. Disclosures Djebbari: Takeda: Other: Support with virtual ASH attendance (2020); Sanofi: Other: Honoraria for an education evening for haematologists about isatuximab. Ramasamy: GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Rhoa Mutation Is a Potential Biomarker Associated with Adverse Prognosis and High- Tumor Burden in Patients with Nodal Peripheral Lymphomas with T-Helper Follicular Phenotype (nPTCL-Thf): Data from a Brazilian Retrospective Cohort of Nodal PTCL

Introduction: Nodal PTCL constitute a rare group of aggressive malignancies with heterogeneous clinical-biological presentation and outcomes. In the last decade, its pathophysiological knowledge has been improved, with descriptions of gene mutations associated with epigenetic phenomena (IDH2, TET2 and DNMT3A) and of the RHOA G17V mutation playing a fundamental role in the lymphomagenesis. However, the prognostic impact of these alterations is still controversial, and particularly, in the case of the RHOA mutation, it has never been previously accessed in the literature. Our group has described and validated biomarkers with potential prognostic impact in nPTCL patients, including overexpression of the genes CCNA2, GATA3 and monocytosis in peripheral blood [1,2,3]. The identification of new potential molecular biomarkers can refine the prognostic stratification of these tumors and allow identification of targets for future specific therapies. The aim of this study was to evaluate the frequency and prognostic impact of mutations in the IDH2, TET2, DNMT3 and RHOA genes in Brazilian patients with nPTCL. Methods: In this observational, retrospective and unicentric study, we analyzed the clinical-epidemiological characteristics, outcomes and mutational profile of 59 Brazilian patients with nPTCL treated at the HC-FMUSP, from January 2000 to December 2017. All cases were submitted to centralized histopathological review and were classified according to the criteria proposed by WHO-2008. Cases initially categorized as PTCL/NOS were later reclassified according to WHO-2016 criteria. FFPE-tumor samples from patients with PTCL/NOS, AITL, ALK+/ALCL and ALK-/ALCL were submitted to DNA extraction using QIAmp DNA FFPE kit. For amplification of specific products of target-genes primers flanking the hot spots regions were designed. After this step, the PCR products were submitted to first generation sequencing in 3500 Genetic Analyzer. Absolute and relative frequencies of mutations were accessed for the total cohort and its pathological subtypes. OS and PFS curves were constructed using the Kaplan-Meier method. Log-rank test was used to estimate the prognostic impact of mutations. Results: The clinical-epidemiological characteristics of the 59 Brazilian-patients with nPTCL are summarized in Table 1. With a median follow-up of 3.70 years (0.90-12.4 years), the estimated 2-years OS and PFS were 59.1% and 47.2%, respectively. ORR was 55.9% (33/59), with early relapse rate (&lt; 12 months) of 14.3% (5/59) and global death rate of 52.5% (31/59). In the total cohort, we found a mutation frequency of 3.4% (2/59) for the IDH2 gene, 62.7% (37/59) for DNMT3A, 23.7% (14/59) for RHOA and 50.8% (30/59) for TET2. There was no statistically significant difference in the frequency distribution of IDH2, DNMT3A and TET2 mutations between the different histological subtypes of nPTCL. However, there was a statistical trend towards a higher occurrence of the RHOA mutation in the AITL and PTCL/NOS subtypes (3/9-33.3% and 7/16-43.7%, respectively; p=0.07). Among 7 cases with RHOA mutation classified as PTCL/NOS according WHO-2008 criteria, 6/7 (85.7%) expressed the PD-1 marker in immunohistochemistry, being reclassified as nPTCL with THf phenotype according to WHO-2016 criteria. So, the mutation RHOA was predominantly found in THf cell-derived neoplasms in our cohort. The mutational status of DNMT3A, RHOA and TET2 genes had no prognostic impact on OS, with p=0.85, p=0.13 and p=0.95, respectively. The same was observed in relation to PFS for the DNMT3A (p=0.70) and TET2 (p=0.52) mutations. However, the presence of the RHOA mutation was associated with the unfavorable PFS in our cohort (HR:1.98, p=0.05). We observed 2-year PFS of 28.6% (95% CI: 8.8-52.4%) for mutated-RHOA cases versus 52.9% (95% CI: 37.3-66.3%) for wild-type-RHOA patients (p=0.05) [Figure 1]. We also demonstrated that RHOA mutation was a predictor of lower ORR to first-line therapy (p=0.01) and was associated with high tumor burden (p=0.03) [Figure 2]. Conclusion: In this study, for the first time was demonstrated the unfavorable prognostic impact of the RHOA mutation in patients with nPTCL-Thf (AITL and nPTCL-THf), making it a potential molecular biomarker predictor of poor-PFS, associated with resistance to primary therapy and with high tumor burden. Such results are preliminary and will need to be validated in series with a larger number of cases. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

TP53 Mutations, Deletions, and CN-LOH: Comparison of TP53 single Hit and Double Hit Events and Their Impact on Prognosis in Hematological Malignancies

Background: TP53 is altered in ~50% of human cancers. Alterations mainly include mutations and/or deletions, but also copy-neutral loss of heterozygosity (CN-LOH) was reported. Frequently, both TP53 alleles are altered (by mutation + deletion, mutation + CN-LOH or ≥2 mutations), leading to a "double hit" event. Aim: Analysis of TP53 aberrations using WGS in 4646 cases with 29 different hematological malignancies, comparing (1) the frequencies of TP53 alterations, (2) occurrence of single hit vs. double hit, (3) correlation with complex karyotype and (4) impact on survival. Methods: Whole-genome sequencing (WGS) was performed for all 4,646 patients (median coverage 100x). 151bp paired-end reads were generated on NovaSeq 6000 and HiSeqX machines (Illumina, San Diego, CA). As no sample specific normal tissue was available, a so-called Tumor/Unmatched normal (TUN) workflow was used to reduce technical artefacts and germline calls. All reported p-values are two-sided and were considered significant at p&lt;0.05. Results: In the total cohort of 4,646 cases, in 582 (13%) at least one alteration (alt) involving TP53 was detected (comprising mutations (mut), deletions (del) and CN-LOH (LOH); Fig 1A,B). Cases were categorized as follows: cases with (1) 1 TP53 mut only (n=166), (2) del only (n=100), (3) LOH only (n=15), constituting the single hit events. Further, (4) cases with mut+del (might include 1 or more mut, n=211), cases with mut+LOH (≥1 mut, n=41), cases with ≥2 mut only (without del or LOH, n=49), resulting in double hit events (Fig 1B). Regarding the respective entities, high frequencies of TP53 alt were mainly detected in lymphoid malignancies (e.g. HGBL, MPAL, vHZL, MZL, MCL), whereas they were infrequent or absent in many myeloid malignancies (e.g. aCML, MPN, CMML, CML, MLN_eo; Fig 1A). For further analysis, only entities in which &gt;10 cases showed TP53 alt events were used. Comparison of single hit vs. double hit revealed that T-NHL, MM, MPN and MDS predominantly showed a single hit, whereas the double hit was frequent in MPAL, MZL, MDS/MPN-U, CLL and MCL cases (Fig 1A). However, the type of double hit differed between myeloid and lymphoid malignancies, as myeloid neoplasms showed a high frequency of cases with ≥2 mut only, whereas in many lymphoid malignancies the double hit was predominantly generated by mut+del (Fig 1A,C). All TP53-associated events (mut, del, LOH and the respective combinations) were found to be associated with a complex karyotype in the total cohort (LOH: 14% complex karyotype in cases without TP53 alt vs. 59% in cases with TP53 alt, p&lt;0.001). This association was also detected for most of the selected entities (exceptions: MZL, T-NHL). Regarding overall survival (OS), in the total cohort, all events involving TP53 impact on OS (TP53 alt: 22 months vs. 84 months, p&lt;0.001; TP53 mut: 20 vs. 82 months, p&lt;0.001; TP53 del: 20 vs. 79 months, p&lt;0.001; TP53 LOH: 20 vs. 75 months, p&lt;0.001). Moreover, although the single hit already impacts on OS, the double hit leads to an even inferior outcome (no hit vs. single hit vs. double hit: 84 vs. 39 vs. 14 months, p&lt;0.001). In the selected entities, an influence of TP53 alt on OS was detected for all malignancies except HGBL, MZL and T-NHL, for which also the presence of a double hit did not show an effect on OS. For the majority of the other entities, the double hit leads to a shorter OS than the single hit (as observed for the total cohort), with the exceptions of MCL and MPAL: in these entities, the single hit did not impact on OS, but only a double hit is associated with inferior outcome. Conclusions: (1) Frequency of TP53 alterations and of double hit vs. single hit differs markedly between entities. (2) The kind of TP53 complexity differs between both lineages (double hit in myeloid neoplasms: often ≥2 mut only; in lymphoid malignancies: predominantly mut+del). (3) In 7% (41/582) of cases with TP53 alt, CN-LOH transforms a single hit into a double hit. (4) In the total cohort and in the majority of selected entities (except MZL and T-NHL), TP53 alt are associated with complex karyotype. (5) In the total cohort, all events involving TP53 impact on OS; cases with double hit show an inferior outcome compared to single hit. (6) Regarding OS, the selected entities can be divided into three categories: (i) no influence of TP53 alt (HGBL, MZL, T-NHL); (ii) double hit required for impact on OS (MCL, MPAL); (iii) influence of both single hit and double hit with inferior outcome of double hit (all other). Figure 1 Figure 1. Disclosures Kern: MLL Munich Leukemia Laboratory: Other: Part ownership. Haferlach: MLL Munich Leukemia Laboratory: Other: Part ownership. Haferlach: MLL Munich Leukemia Laboratory: Other: Part ownership.