Homogeneous Cohort Research Articles

Does discontinuing bleomycin due to toxicity increase the risk of lymphoma progression? Real-life data from a homogeneous population of advanced stage Hodgkin lymphoma

Hodgkin Lymphoma (HL) is often curable with ABVD therapy and improving outcomes is a main goal of ongoing research. Bleomycin-associated pneumonitis (BAPT) is a potentially life-threatening complication that necessitates bleomycin discontinuation. We conducted this study on a homogenous cohort of advanced stage HL treated only with ABVD for frontline therapy to assess if bleomycin discontinuation increases the risk of lymphoma progression. After the exclusion of patients who received radiotherapy or other drugs, 106 and 28 patients in the six-cycle ABVD and BAPT groups respectively had similar survival curves for progression and death with a 49-month median follow-up. PFS rates were also very similar at two and four years from diagnosis with 2-year PFS rates of 83.9% and 82.1% (RR = 1.1 95%CI = 0.45–2.2). Outcome comparisons were also similar between the two groups when stratified according to early response assessment with PET/CT. Patients who discontinued bleomycin due to toxicity did not experience an increased risk of progression compared to patients who completed six ABVD cycles.

The paradox of the association between epicardial adipose tissue, infarct size and left ventricular remodelling after ST-segment elevation myocardial infarction: a CMR study

Abstract Background Epicardial adipose tissue (EAT) is a biologically active fat deposit contained below the visceral pericardium. In latest years, EAT has emerged as a predictor of atherosclerosis, coronary artery disease and adverse cardiovascular events. Nevertheless, EAT significance after ST-segment elevation myocardial infarction (STEMI) in acute phase and its association with left ventricular remodelling is unknown. Purpose We aimed to assess the association of cardiac magnetic resonance (CMR)-derived EAT with the extent of infarct size (IS), microvascular obstruction (MVO) and left ventricular remodelling in a homogeneous cohort of STEMI patients. Methods We prospectively included 255 patients discharged after a first reperfused, anterior STEMI. An early CMR (1-week after STEMI) was performed in all patients. EAT volume (mL/m2), left ventricular (LV) end-diastolic and end-systolic indexed volumes (LVEDiV and LVESiV, mL/m2), left ventricular ejection fraction (LVEF, %), infarct size (IS, % of LV mass) and microvascular obstruction (MVO, % of LV mass) were quantified. A subgroup of 195 patients underwent a follow-up (6-month) CMR. Patients were categorized as extensive EAT (>35 mL/m2) or non-extensive EAT (≤35 mL/m2) according to the upper tertile of this parameter. A specific analysis was performed in patients with extensive IS (>30% of LV mass). Results Patients with extensive EAT were older (62±12 vs. 57±13 years, p=0.004), had an increased prevalence of diabetes mellitus (31% vs. 16%, p=0.007) and depicted a worse baseline risk profile (GRACE risk score 138±37 vs. 126±36 points, p=0.02). At 1-week CMR, patients with extensive EAT displayed larger IS (31±17% vs 24±16%, p=0.001), more MVO (1.4 [0-6.2]% vs 0 [0-2.5]% of LV mass, p=0.022) and more myocardial oedema (39±16% vs 32±17% of LV mass, p=0.003). After adjustment for baseline characteristics, EAT was independently associated with IS (standardized beta coefficient=0.30, p<0.001). However, patients with extensive EAT did not show neither larger LV volumes nor more depressed LVEF (p>0.1 for all comparisons). In the extensive IS subgroup (n=69, 27%), patients with extensive EAT depicted less dilated ventricular volumes (LVEDiV 90±26 vs 111±40 mL/m2, p=0.011; LVESiV 51±26 vs 72±36 mL/m2, p=0.009) and higher LVEF (46±13 vs. 38±10%, p=0.007) at 6-month CMR. At 6-month CMR, in a propensity score-matched population (n=170, 85 with extensive EAT and 85 without extensive EAT), EAT was independently associated with more preserved LVEF, and less dilated LVEDiV and LVESiV only in the subgroup of patients with extensive IS (p<0.05 for all comparisons) (Figure 1). Conclusions EAT seems to exert a bimodal effect in patients with anterior STEMI. More extensive EAT is associated with more extensive infarct size in acute phase but, in patients with large IS, those with extensive EAT display less adverse remodelling during follow-up. This "paradox" of EAT after STEMI merits further investigation.Figure 1.

Analysis of predictive factors of unforeseen nodal metastases in resected clinical stage I NSCLC.

Despite notable advances made in preoperative staging, unexpected nodal metastases after surgery are still significantly detected. In this study we aim to analyze the upstaging rate in patients with clinical stage I NSCLC without evidence of nodal disease in the preoperative staging who underwent lobectomy and radical lymphadenectomy. Patients who underwent lobectomy and systematic lymphadenectomy for clinical stage I NSCLC were evaluated. Exclusion criteria included the neoadjuvant treatment, incomplete resection and no adherence to preoperative guidelines. A total of 297 patients were included in the study. 159 patients were female, and the median age was 68 (61 - 73). The variables that showed a significant correlation with the upstaging rate at the univariate analysis were the number of resected lymph nodes and micropapillar/solid adenocar-cinoma subtype. This result was confirmed in the multivariate analysis with a OR= 2.545 (95%CI 1.136-5.701; p=0.02) for the number of resected lymph nodes and a OR=2.717 (95%CI 1.256-5.875; p=0.01) for the high-grade pattern of adenocarcinoma. Our results showed that in a homogeneous cohort of patients with clinical stage I NSCLC, the number of resected lymph nodes and the histological subtype of adenocarcinoma can significantly be associated with nodal metastasis.

Is Replantation Associated With Better Hand Function After Traumatic Hand Amputation Than After Revision Amputation?

Replantation is an established treatment for traumatic upper extremity amputation. Only a few studies, however, have assessed the patient-reported outcomes of replantation, and the findings of these studies have been conflicting. (1) Is replantation associated with better hand function than revision amputation? (2) Is replantation associated with better health-related quality of life, less painful cold intolerance, and more pleasing hand esthetics than revision amputation after a traumatic hand amputation? In this retrospective, comparative study, we collected the details of all patients who sustained a traumatic upper extremity amputation and were treated at the study hospital. Between 2009 and 2019, we treated 2250 patients, and we considered all patients who sustained a traumatic amputation of two or more digital rays or a thumb as potentially eligible. Based on that, 15% (334 of 2250) were eligible; a further 2% (8 of 334) were excluded because of a subsequent new traumatic amputation or bilateral amputation, and another 22% (72 of 334) refused participation, leaving 76% (254 of 334) for analysis here. The primary outcome was the DASH score. Secondary outcomes included health-related quality of life (EuroQOL-5D [EQ-5D-5L] Index), painful cold intolerance (the Cold Intolerance Symptom Severity score), and hand esthetics (the Michigan Hand Questionnaire aesthetic domain score). The minimum follow-up time for inclusion was 18 months. Patients were classified into two treatment groups: replantation (67% [171 of 254], including successful replantation in 84% [144 of 171] and partially successful replantation in 16% [27 of 171], in which some but not all of the replanted tissue survived), and revision (complete) amputation (33% [83 of 254], including primary revision amputation in 70% [58 of 83] and unsuccessful replantation followed by secondary amputation in 30% [25 of 83]). In this cohort, replantation was performed if possible, and the reason for choosing primary revision amputation over replantation was usually an amputated part that was too severely damaged (15% [39 of 254]) or was unattainable (2% [4 of 254]). Some patients (3% [8 of 254]) refused to undergo replantation, or their health status did not allow replantation surgery and postoperative rehabilitation (3% [7 of 254]). Gender, age (mean 48 ± 17 years in the replantation group versus 50 ± 23 years in the revision amputation group; p = 0.41), follow-up time (8 ± 4 years in the replantation group versus 7 ± 4 years in the revision amputation group; p = 0.18), amputation of the dominant hand, smoking, extent of tissue loss, or presence of arterial hypertension did not differ between the groups. Patients in the replantation group less frequently had diabetes mellitus (5% [8 of 171] versus 12% [10 of 83]; p = 0.03) and dyslipidemia (4% [7 of 171] versus 11% [9 of 83]; p = 0.04) than those in the revision group and more often had cut-type injuries (75% [129 of 171] versus 60% [50 of 83]; p = 0.02). After controlling for potential confounding variables such as age, injury type, extent of tissue loss before treatment, and accident of the dominant hand, replantation was not associated with better DASH scores than revision amputation (OR 0.82 [95% confidence interval (CI) 0.50 to 1.33]; p = 0.42). After controlling for potential cofounding variables, replantation was not associated with better EQ-5D-5L Index scores (OR 0.93 [95% CI 0.56 to 1.55]; p = 0.55), differences in Cold Intolerance Symptom Severity scores (OR 0.85 [95% CI 0.51 to 1.44]; p = 0.79), or superior Michigan Hand Questionnaire esthetic domain scores (OR 0.73 [95% CI 0.43 to 1.26]; p = 0.26) compared with revision amputation. Replantation surgery was conducted, if feasible, in a homogenous cohort of patients who underwent amputation. If the amputated tissue was too severely damaged or replantation surgery was unsuccessful, the treatment resulted in revision (complete) amputation, which was not associated with worse patient-reported outcomes than successful replantation. These results contradict the assumed benefits of replantation surgery and indicate the need for credible evidence to better guide the care of these patients. Level III, therapeutic study.

The CODECS study: COgnitive DEficits in Cerebellar Stroke

Part of the extra-pyramidal system, the cerebellum is more and more recognized by its non-motor functions known as the cerebellar cognitive affective syndrome. Several studies have identified disturbances specifically in executive and attentional functions after focal cerebellar lesions. However, most studies were performed in small and heterogeneous patient groups. Furthermore, there is a substantial variation in the methodology of assessment. Here, we present the results of a large and homogeneous cohort of patients with isolated uniform cerebellar lesions. After three months post-stroke all patients underwent structural neuroimaging to confirm an isolated lesion and were given neuropsychological testing. The results show that cerebellar lesions relate to mild but long-term cognitive impairment in a broad spectrum of neurocognitive functions compared to normative values. These findings confirm involvement of the cerebellum in cognitive processing and supports the theory of ‘dysmetria of thought’ based upon uniform cerebellar processing in multiple cognitive domains. This study highlights the following results: 1-Cognitive impairments after isolated cerebellar stroke is confirmed in several cognitive domains. 2-Semantic and phonemic fluency are most affected in cerebellar stroke patients. 3-Verbal deficits show an age-independent long term effect post-stroke and should be studied further in depth. 4-Cognitive disorders after cerebellar stroke are more prominent in women than men.

Prognostic impact of lymph node characteristics after therapeutic neck dissection for classic N1 papillary thyroid cancer.

The impact of lymph node characteristics on mortality and recurrence remains controversial. This study evaluated the prognostic impact of lymph node characteristics in a large, homogenous cohort of patients with therapeutic neck dissection for clinically N1 classic papillary thyroid cancer (PTC). All consecutive adult patients with therapeutic central and lateral neck dissection for PTC at a French referral centre were prospectively enrolled from January 2000 until June 2021. The primary outcome was the impact of lymph node characteristics in predicting a disease event (persistence or recurrence), using univariable and multivariable logistic regression modelling. A total of 462 patients were included. Lymph node capsular rupture was seen in 260 patients (56.3 per cent). Median maximum lymph node size was 15 (i.q.r. 9-23) mm. The median central, lateral, and total lymph node ratio (LNR) was 0.50 (i.q.r. 0.22-0.75), 0.15 (i.q.r. 0.07-0.29), and 0.26 (i.q.r. 0.14-0.41), respectively. After a median follow-up of 93 (i.q.r. 50-149) months, 182 (39.4 per cent) patients had a disease event. After multivariable analysis, the number of harvested lymph node >35 (OR 2.33 (95 per cent c.i. 1.10-4.95)), presence of lymph node capsular rupture (OR 1.92 (1.17-3.14)), and total LNR >0.20 (OR 2.37 (1.08-5.19)) and >0.40 (OR 4.92 (1.61-15.03)) predicted a disease event. An LNR of 0.20 predicted a disease event with a sensitivity of 80.8 per cent and a specificity of 50.4 per cent. Disease persistence or recurrence after thyroidectomy with therapeutic neck dissection for classic PTC with preoperative nodal disease appears to depend on number of harvested lymph node, presence of lymph node capsular rupture, and total LNR.

Expansion of extrafollicular B and T cell subsets in childhood-onset systemic lupus erythematosus.

Most childhood-onset SLE patients (cSLE) develop lupus nephritis (cLN), but only a small proportion achieve complete response to current therapies. The prognosis of children with LN and end-stage renal disease is particularly dire. Mortality rates within the first five years of renal replacement therapy may reach 22%. Thus, there is urgent need to decipher and target immune mechanisms that drive cLN. Despite the clear role of autoantibody production in SLE, targeted B cell therapies such as rituximab (anti-CD20) and belimumab (anti-BAFF) have shown only modest efficacy in cLN. While many studies have linked dysregulation of germinal center formation to SLE pathogenesis, other work supports a role for extrafollicular B cell activation in generation of pathogenic antibody secreting cells. However, whether extrafollicular B cell subsets and their T cell collaborators play a role in specific organ involvement in cLN and/or track with disease activity remains unknown. We analyzed high-dimensional mass cytometry and gene expression data from 24 treatment naïve cSLE patients at the time of diagnosis and longitudinally, applying novel computational tools to identify abnormalities associated with clinical manifestations (cLN) and disease activity (SLEDAI). cSLE patients have an extrafollicular B cell expansion signature, with increased frequency of i) DN2, ii) Bnd2, iii) plasmablasts, and iv) peripheral T helper cells. Most importantly, we discovered that this extrafollicular signature correlates with disease activity in cLN, supporting extrafollicular T/B interactions as a mechanism underlying pediatric renal pathogenesis. This study integrates established and emerging themes of extrafollicular B cell involvement in SLE by providing evidence for extrafollicular B and peripheral T helper cell expansion, along with elevated type 1 IFN activation, in a homogeneous cohort of treatment-naïve cSLE patients, a point at which they should display the most extreme state of their immune dysregulation.

Hypovitaminosis D in persons with Down syndrome and autism spectrum disorder

BackgroundPlasma levels of vitamin D have been reported to be low in persons with Down syndrome (DS) and existing data is limited to small and homogenous cohorts. This is of particular importance in persons with DS given the high rates of autoimmune disease in this population and the known relationship between vitamin D and immune function. This study sought to investigate vitamin D status in a multi-center cohort of individuals with DS and compare them to individuals with autism spectrum disorder (ASD) and neurotypical (NT) controls.MethodsA retrospective, multi-center review was performed. The three sites were located at latitudes of 42.361145, 37.44466, and 34.05349. Patients were identified by the International Classification of Diseases (ICD)-9 or ICD-10 codes for DS, ASD, or well-child check visits for NT individuals. The first vitamin D 25-OH level recorded in the electronic medical record (EMR) was used in this study as it was felt to be the most reflective of a natural and non-supplemented state. Vitamin D 25-OH levels below 30 ng/mL were considered deficient.ResultsIn total, 1624 individuals with DS, 5208 with ASD, and 30,775 NT controls were identified. Individuals with DS had the lowest mean level of vitamin D 25-OH at 20.67 ng/mL, compared to those with ASD (23.48 ng/mL) and NT controls (29.20 ng/mL) (p < 0.001, 95% CI: −8.97 to −6.44). A total of 399 (24.6%) individuals with DS were considered vitamin D deficient compared to 1472 (28.3%) with ASD and 12,397 (40.3%) NT controls (p < 0.001, 95% CI: −5.43 to −2.36). Individuals with DS with higher body mass index (BMI) were found to be more likely to have lower levels of vitamin D (p < 0.001, 95% CI: −0.3849 to −0.1509). Additionally, having both DS and a neurologic diagnosis increased the likelihood of having lower vitamin D levels (p < 0.001, 95% CI: −5.02 to −1.28). Individuals with DS and autoimmune disease were much more likely to have lower vitamin D levels (p < 0.001, 95% CI: −6.22 to −1.55). Similarly, a history of autoimmunity in a first-degree relative also increased the likelihood of having lower levels of vitamin D in persons with DS (p = 0.01, 95% CI: −2.45 to −0.63).ConclusionsIndividuals with DS were noted to have hypovitaminosis D in comparison to individuals with ASD and NT controls. Associations between vitamin D deficiency and high BMI, personal autoimmunity, and familial autoimmunity were present in individuals with DS.

Large sample size and nonlinear sparse models outline epistatic effects in inflammatory bowel disease

BackgroundDespite clear evidence of nonlinear interactions in the molecular architecture of polygenic diseases, linear models have so far appeared optimal in genotype-to-phenotype modeling. A key bottleneck for such modeling is that genetic data intrinsically suffers from underdetermination (p gg n). Millions of variants are present in each individual while the collection of large, homogeneous cohorts is hindered by phenotype incidence, sequencing cost, and batch effects.ResultsWe demonstrate that when we provide enough training data and control the complexity of nonlinear models, a neural network outperforms additive approaches in whole exome sequencing-based inflammatory bowel disease case–control prediction. To do so, we propose a biologically meaningful sparsified neural network architecture, providing empirical evidence for positive and negative epistatic effects present in the inflammatory bowel disease pathogenesis.ConclusionsIn this paper, we show that underdetermination is likely a major driver for the apparent optimality of additive modeling in clinical genetics today.

The Effect of Package Time on Locally Advanced Oral Cavity Cancer Outcomes

Oral cavity cancer (OCC) with adverse pathologic features is treated with adjuvant radiation (RT) following definitive surgical resection. The 5-year overall survival (OS) in locally advanced OCC patients receiving adjuvant RT has remained stagnant at 60% for over 30 years. Although pathologic risk factors are well-established, the effect of clinical variables such as treatment package time (TPT) in the modern era of radiation and systemic agents is unclear. Examining a large, homogenous cohort of OCC patients, we hypothesized that TPT can predict OS and event free survival (EFS). A retrospective review of 359 adult patients with OCC treated with surgery and adjuvant RT with or without concurrent chemotherapy from 2012-2022 was performed at a single, high-volume center. Those without definitive surgery, treated to <50 Gy, or with a history of prior RT were excluded. TPT was defined as time from surgery to completion of RT. Other variables considered were sex, race, smoking status, AJCC 8 pathologic stage, perineural invasion (PNI), lymphovascular invasion (LVI), margin positivity, extranodal extension (ENE), and hospitalization between surgery and RT. Log rank tests were performed for OS and EFS where TPT was dichotomized into short (<97.5 days) and long (>97.5 days) groups based on the median TPT of the cohort. Univariate (UVA) and multivariate (MVA) cox regression analyses were performed for OS and EFS. A total of 234 patients met inclusion criteria. Median OS was 81.6 months. Median EFS was 50.0 months. Median OS was 51.1 months in the longer TPT group and was not reached in the shorter TPT group. Median EFS was greater with shorter TPT (72.6 vs 31.3 months). The longer TPT group had worse OS and EFS probabilities than the shorter TPT group (p = 0.006 and p = 0.059, respectively). On UVA, factors significantly associated with OS were TPT (p = 0.006), former/current smoker status (p = 0.003 and p = 0.011, respectively), pathologic stage IV (p<0.001), positive PNI (p<0.001) or LVI (p = 0.005), and ENE (p<0.001). On MVA for OS, shorter TPT (p = 0.026), former smoker status (p = 0.009), pathologic stage IV (p = 0.026), positive PNI (p = 0.009), and ENE (p = 0.05), remained significant. On UVA, factors significantly associated with EFS were former/current smoker status (p = 0.01/p = 0.04), pathologic stage IV (p<0.001), pT1/T2 (p = 0.018), positive PNI (p = 0.011) or ENE (p<0.001), and concurrent chemotherapy (p = 0.001). On MVA, former smoker status (p = 0.035) and positive PNI (p = 0.018) remained significant. Notably, of the 130 patients requiring hospitalization between surgery and radiation, 101 (78%) were prior/current smokers. In this large cohort of locally advanced OCC patients, TPT <97.5 days is associated with improved OS and EFS. Smoking history should be further explored for its potential contribution to treatment delay. Multidisciplinary coordination should be encouraged to minimize TPT.

Deltoid Muscle Tension Alterations Post Reverse Shoulder Arthroplasty: An Investigation Using Shear Wave Elastography.

This study aimed to evaluate the utility of shear wave elastography (SWE) in assessing changes in deltoid muscle properties following reverse shoulder arthroplasty (RSA). Our cohort consisted of 18 patients who underwent RSA due to various conditions, including osteoarthritis, cuff arthropathy, and irreducible proximal humeral fractures. Pre- and postoperative muscle elasticity and stiffness were measured using SWE and were compared with functional outcomes and radiological parameters. Our results showed significant changes in deltoid muscle elasticity after RSA, particularly in the anterior and middle portions. However, these alterations were not correlated with postoperative functional outcomes or specific radiological parameters. The study also underscored the potential of SWE for future applications, including the preoperative assessment of deltoid function, postoperative monitoring, and intraoperative use for optimal component positioning during RSA. Further research, involving larger, more homogeneous patient cohorts is needed to confirm these findings and to explore the potential influence of these changes on the biomechanical design of implants and prosthesis positioning in RSA.

Transplantation Outcomes of Myelofibrosis with Busulfan and Fludarabine Myeloablative Conditioning

Outcomes of myelofibrosis (MF) with allogeneic stem cell transplantation (allo-SCT) have improved over the past decade, related in part to advances in supportive treatments and conditioning regimens. Several factors are known to predict transplantation outcomes. However, most studies lack homogeneity in conditioning regimens used, limiting their ability to assess prognostic factors on transplantation outcomes. We aimed to identify the risk factors that predict transplantation outcomes in patients with MF who underwent matched or mismatched allo-SCT using a uniform myeloablative conditioning regimen consisting of busulfan and fludarabine with tacrolimus and methotrexate-based graft-versus-host disease prophylaxis. This single-center study included patients with MF who underwent allo-SCT with a matched unrelated donor (MUD), matched related donor (MRD), or mismatched unrelated donor (MMUD) and received busulfan and fludarabine conditioning with methotrexate/tacrolimus-based GVHD prophylaxis. Sixty-5 patients with MF met the study criteria and were included in our analysis. At a median follow-up of 35.6 months, the 3-year cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and overall survival (OS) for all study patients were 27%, 20%, and 65%, respectively. In a multivariable analysis for CIR, prior use of JAK inhibitors was significantly associated with a decreased risk of relapse (hazard ratio [HR], .33; 95% confidence interval [CI], .11 to .99; P = .048). For NRM, Hematopoietic Cell Transplantation Comorbidity Index (≥3 versus <3; HR, 10.09; 95% CI, 2.09 to 48.76; P = .004) and donor type (MUD versus MRD: HR, 5.38; 95% CI, 1.14 to 25.30; P = .033; MMUD versus MRD: HR, 10.73; 95% CI, 1.05 to 109.4; P = .045) were associated with an increased risk of mortality. Likewise for OS, HCT-CI (≥3 versus <3; HR, 3.31; 95% CI, 1.22 to 8.99; P = .019) and donor type (MMUD versus MRD: HR, 5.20; 95% CI, 1.35 to 19.98; P = .016) were significantly associated with inferior survival. Longer time from diagnosis to allo-SCT seemed to confer worse survival, but the difference did not reach statistical significance (>12 months versus ≤12 months: NRM: HR, 7.20; 95% CI, .96 to 53.94; P = .055; OS: HR, 2.60; 95% CI, .95 to 7.14; P = .06). In a homogenous cohort of MF patients uniformly treated with busulfan/fludarabine myeloablative conditioning and methotrexate-based GVHD prophylaxis, we show that donor choice and HCT-CI are the 2 strongest predictors for improved survival after allo-SCT.

Response assessment of post-treatment head and neck cancers to determine further management using NI-RADS (Neck Imaging Reporting and Data System): a subgroup analysis of a randomized controlled trial.

Interpreting complex post-treatment changes in head and neck cancer (HNC) is challenging with further added perplexity due to variable interobserver interpretation and hence evolved the NI-RADS lexicon. We evaluated the accuracy of NI-RADS in predicting disease status on 1st post-treatment follow-up CECT in a homogenous cohort of those who received only chemoradiation. Retrospective analysis of imaging was done for LASHNC patients who received radical chemoradiation in an open-label, investigator-initiated, phase 3 randomized trial (2012-2018) randomly assigned to either radical radiotherapy with concurrent weekly cisplatin (CRT) or CRT with the same schedule plus weekly nimotuzumab (NCRT). 536 patients were accrued, and 74 patients who did not undergo PET/CECT after 8 weeks post-CRT were excluded. After assessing 462 patients for eligibility to allocate NI-RADS at primary and node sites, 435 cases fell in the Primary disease cohort and 412 cases in the Node disease cohort. We evaluated sensitivity, disease prevalence, the positive and negative predictive value of the NI-RADS lexicon, and accuracy, which were expressed as percentages. We also prepared flow charts to determine concordance with allocated NI-RADS category and established accuracy with which it can identify disease status. Out of 435 primary disease cohort, 92%, 55%, 48%,70% were concordant and had 100%, 72%, 70%, 82% accuracy in NI-RADS1 (n=12), NI-RADS2 (n=261), NIRADS3 (n=105), and NI-RADS 4 (n=60) respectively. Out of 412 nodes disease cohort, 95%, 90%, 48%, 70%were concordant and had 92%, 97%, 90%, 67% accuracy in NI-RADS1 (n=57), NI-RADS2 (n=255), NI-RADS3 (n=105) and NI-RADS4 (n=60) respectively. % concordance of PET/CT and CECT across all primary and node disease cohorts revealed that PET/CT was 91% concordant in primary NI-RADS2 as compared to 55% concordance of CECT whereas concordance of CECT was better with 57% in primary NI-RADS3 cohort as compared to PET/CT concordance of 41%. The accuracy with which the NI-RADS lexicon performed in our study at node sites was better than that at the primary site. There is a great scope of research to understand if CECT performs better over clinical disease status in NI-RADS 3 and 4 categories. Further research should be carried out to understand if PET/CECT can be used for close interval follow-up in stage III/IV NI-RADS 2 cases.

Medium term donor-site morbidity after tricortical iliac crest graft harvesting for foot and ankle indications

Purpose of the studyThe retrospective study aimed at assessment of donor site morbidity of tricortical iliac crest graft harvest for foot and ankle indications in a single-surgeon, single-technique group of patients. Materials and methodsConsecutive patients undergoing procedures in foot and ankle requiring grafting from iliac crest were contacted with telephoned questionnaire within a second year post surgery. ResultsAmong the group of 37 patients, 100% follow-up has been achieved. One patient reported continued pain at the donor site, one case of hyperesthesia around the approach and one case of hypoesthesia of lateral cutaneous nerve of the thigh were reported. DiscussionData regarding complications of tricortical bone graft harvest from iliac crest is varied. Long term pain has been reported in up to 29% of cases. Variability of information negatively influences informed consent process. We report the results of homogeneous cohort of patients operated for foot and ankle indications. ConclusionHarvesting of tricortical anterior iliac graft for foot and ankle indications carries minimal risk of long term pain at the donor site.

P11.65.B TEMPORAL MUSCLE THICKNESS AS A PROGNOSTIC MARKER IN A REAL-LIFE COHORT OF NEWLY DIAGNOSEDMGMT PROMOTER METHYLATED GLIOBLASTOMA PATIENTS: A MULTICENTRIC IMAGING ANALYSIS

Abstract BACKGROUND In cranial magnetic resonance imaging (MRI) assessed temporal muscle thickness (TMT) correlates with lumbar skeletal muscle mass, which serves as a surrogate marker of sarcopenia. Prior research has identified TMT as a prognostic marker in glioblastoma. However, incorporation into clinical practice is challenging due to the heterogeneity of previous studies and the absence of established cutoff values. To address this, we conducted a multicenter analysis to validate recently proposed sex-specific cutoff values in a homogeneous cohort of newly diagnosed MGMT promoter-methylated glioblastoma patients uniformly treated under real-life conditions with combined CCNU/temozolomide. We also included a balanced control cohort for comparison. MATERIAL AND METHODS TMT was measured at baseline using initial preoperative and postoperative MRI and during the course of the disease using the first MRI after completion of radiotherapy in the first therapy-line. Using TMT and previously reported cutoff values from the literature, patients were classified into "at risk of sarcopenia" or "normal muscle status" cohorts. To correlate TMT with survival, we conducted Kaplan-Meier and multivariable Cox regression analyses. RESULTS A total of 126 patients were analyzed, with 66 patients treated with combined CCNU/temozolomide and 60 patients treated with temozolomide single-drug treatment. In both cohorts, patients with normal muscle mass at baseline had significantly longer survival. Specifically, in the CCNU/temozolomide cohort median progression-free survival (mPFS) was 16.7 months in the normal muscle mass group versus 6.8 months in the at-risk group (p=0.0008); median overall survival (mOS) was 44.2 months in the normal muscle mass group versus 16.7 months in the at-risk group (p=0.0046). In the temozolomide single-drug cohort, mPFS was 12.4 months in the normal muscle mass group versus 7.7 months in the at-risk group, and mOS was 29.5 months in the normal muscle mass group versus 17.4 months in the at-risk group (p=0.0006). Using multivariable Cox regression analysis, we found normal muscle mass (HR: 0.39, 95% CI: 0.23-0.66; p=0.0003) and initial age at diagnosis of less than 50 years (HR: 0.42, 95% CI: 0.22-0.79; p=0.0067) were statistically significant prognostic markers. Longitudinally, patients with lacking TMT decline during the course of the disease had the best survival outcomes. CONCLUSION This analysis suggests TMT to serve as a prognostic marker in glioblastoma patients treated with CCNU/temozolomide or single-drug treatment with temozolomide. However, for TMT assessment to be implemented in a generalizable manner, such as for patient selection for therapeutic measures, further validation in prospective controlled trials is necessary.

P08.04.B DOES PSYCHO-ONCOLOGICAL CARE AFFECT HEALTH-RELATED QUALITY OF LIFE AND PATIENT AND CAREGIVER SATISFACTION IN IDH WILD-TYPE GLIOMA? - A PROSPECTIVE STUDY

Abstract BACKGROUND Isocitrate dehydrogenase wild-type (IDHwt) gliomas are uncurable primary tumors of the brain and impose a high burden on affected patients and caregivers. In addition to neurological symptoms, changes in cognition and personality are common and should be diagnosed and treated early. About 75% of patients with brain tumors suffer from psychosocial distress at their first consultation. Health-related quality of life (HR-QoL) is significantly reduced by anxiety and negative mood, following glioma diagnosis. Brain tumor diagnosis also affects caregivers negatively. Recent publications show that caregiver and patient satisfaction influence each other, with caregivers generally being less satisfied than patients. In addition to specific tumor and symptomatic therapy, psycho-oncological care is an important element in a comprehensive treatment approach and may lead to increased HR-QoL and patient and caregiver satisfaction. However, there are few prospective datasets focusing on these aspects. MATERIAL AND METHODS We investigated the impact of psycho-oncological care on HR-QoL and patient and caregiver satisfaction in a large brain tumor center. Data from the regional brain tumor registry and electronic medical charts were used to compile the prospective patient cohort. Standardized questionnaires were used to investigate HR-QoL (EORTC QLQ C-30 and BN-20) and satisfaction (EORTC PATSAT-C33). Univariable and multiple linear regression analysis was applied to test the influence of psycho-oncological care on both aspects. RESULTS A homogenous cohort of 61 patients was investigated, of whom 29 (47.5%) received psycho-oncological care. We analyzed 141 EORTC QLQ-C30, 139 EORTC QLQ-BN20, 129 EORTC PATSAT-C33 questionnaires from patients, and 115 EORTC PATSAT-C33 questionnaires from caregivers. We show that patients who received at least one psycho-oncological consultation had significantly worse role functioning (p = 0.001) and a negatively influenced global health status (p = 0.038). Psycho-oncological care had no significant correlation with the satisfaction of patients. Caregivers of patients with psycho-oncological care documented inferior satisfaction with information exchange of doctors (p = 0.036). CONCLUSION We conclude that receiving psycho-oncological care is associated with changes in HR-QoL and patient and caregiver satisfaction. Utmost efforts should be made to integrate intensively and frequently psycho-oncological care on a daily-practice basis. It will be subject of future prospective studies to investigate kind and frequency of interventions that are suited to improve HR-QoL and treatment satisfaction in patients with IDHwt gliomas and their caregivers, and how to complement supportive therapies better to achieve optimal psychosocial outcomes for these patients and their caregivers.

Call for standardization in assessment and reporting of muscle and adipose change using computed tomography analysis in oncology: A scoping review.

Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta-analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative-intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta-analysis. Studies that measured computed tomography-defined SM and/or AT change in adult patients during palliative-intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm2 /m2 , cm2 or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex-specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta-analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care.

Retroperitoneoscopic adrenalectomy may be superior to laparoscopic transperitoneal adrenalectomy in terms of costs and profit: a retrospective pair-matched cohort analysis

BackgroundA direct comparison of the cost–benefit analysis of retroperitoneoscopic adrenalectomy (RPA) versus the minimally invasive transperitoneal access (LTA) approach is currently lacking. We hypothesized that RPA is more cost effective than LTA; promising significant savings for the healthcare system in an era of ever more limited resources.MethodsWe performed a monocentric retrospective observational cohort study based on data from our Endocrine Surgery Registry. Patients who were operated upon between 2019 and 2022 were included. After pair-matching, both cohorts (RPA vs. LTA) were compared for perioperative variables and treatment costs (process cost calculation), revenue and profit.ResultsTwo homogenous cohorts of 43 patients each (RPA vs. LTA) were identified following matching. Patient characteristics between the cohorts were comparable. In terms of both treatment-associated costs and profit, the RPA procedure was superior to LTA (costs: US$5789.99 for RPA vs. US$6617.75 for LTA, P = 0.043; profit: US$1235.59 for RPA vs. US$653.33 for LTA, P = 0.027). The duration of inpatient treatment and comorbidities significantly influenced the cost of treatment and the overall profit.ConclusionsRPA appears not only to offer benefits over LTA in terms of perioperative morbidity and length of hospital stay, but also has a superior financial cost/benefit profile.Graphical abstract

Hormonal Pretreatment for Ovarian Stimulation: A Narrative Review

Introduction: Assisted reproductive technologies are necessary and important for the management of infertility and can be applied with and without the use of strategies such as hormonal pretreatment. However, there is a discussion in the literature on whether hormonal pretreatment in ovarian stimulation protocols can improve the outcome of oocytes and embryos. This study aimed to conduct an integrative review of hormonal pretreatment and its impact on women undergoing assisted reproduction procedures. Methods: We made searches in the PubMed and the Cochrane Library databases. The inclusion criteria were articles published in peer-reviewed journals in English, Portuguese, or Spanish from January 1, 2010 to December 31, 2021 and available as free full texts. We excluded gray literature works, including term papers, theses, and dissertations. We used a narrative synthesis for data analysis. Results: The 189 articles retrieved from the two databases (2010-2021) were narrowed down to eight articles. In most studies, pretreatment seems to play a role beyond stimulation that includes an early inhibition of the FSH peak, a more homogeneous cohort, and better results. Conclusions: Using a pretreatment with combined oral contraceptives (COC) produces conflicting results in assisted reproduction. The COC improves the quantity and quality of eggs, but it neither benefits nor harms reproductive outcomes. Also, the use of COC has contradictory results regarding clinical pregnancy

Serial measurements of SIRS criteria to identify unique phenotypes of sepsis: A Microbiologic Approach

Introduction: The utility of serial scoring systems in identifying distinct sepsis phenotypes remains unknown. Methods: Eligible adults were classified into culture-positive (Cx+) and culture-negative (Cx-) groups alongside pre-defined culture subgroups. Average SIRS &amp; SEP (novel scoring system) scores were calculated at t = 0 and hours 3,6,12 &amp; 24 before and after t = 0. The primary outcome was a difference in SIRS/SEP scores amongst those that were Cx+ or Cx- at any time point. Secondary outcomes were comparing total and component SIRS/SEP scores in microbiologic subgroups over serial time points. Results: 4,701 Cx+ and 3254 Cx- patients met eligibility criteria. Statistically significant differences were seen in the average SIRS score between Cx + and Cx- groups at hours six (Cx+ 1.40+1.04 vs Cx- 1.35+1.01) &amp; 12 (Cx+ 0.95+0.95 vs Cx- 0.90+0.90) after t = 0. The hematologic, urologic, and neurologic subgroups had significant differences at numerous time points before and after T = 0. Similar findings were observed with the SEP scores. Cx+ and Cx- groups (including subgroups) consistently doubled both SIRS/SEP scores before t = 0 with an eventual return to baseline values after T = 0 but at different gradients. Conclusion: Significant differences in SIRS/SEP scores were seen in Cx+ &amp; Cx- patients at sequential time points. This microbiologic approach in homogenous culture cohorts has the potential to identify distinct phenotypes of sepsis efficiently and practically. Consistent increases in SIRS/SEP scores before t = 0 and sequential decreases after t = 0 may allow for early detection, intervention, and provision for real-time monitoring of therapeutic responses in patients with concerns for sepsis.