Landmark Analysis Research Articles

Correlation between immune-related adverse events and clinical outcomes in patients treated with first-line nivolumab plus chemotherapy for advanced gastric or gastroesophageal junction cancer: A multi-center retrospective study in Japan.

439 Background: The CheckMate 649 trial and ATTRACTION-4 trial showed the efficacy of first-line nivolumab plus chemotherapy (Nivo-CT) for advanced gastric or gastroesophageal junction (GEJ) cancer. Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with survival benefit in patients with solid tumors. However, there were few data on correlation between irAEs and efficacy of first-line Nivo-CT for advanced gastric or GEJ cancer. Methods: This multi-center retrospective study included patients with histologically confirmed advanced gastric or GEJ adenocarcinoma who were started on first-line Nivo-CT between December 2021 and December 2023. We divided the patients into two groups according to occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group) and assessed the efficacy in both groups. Efficacy was evaluated by overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Landmark analysis at 2 months after initiating Nivo-CT was performed to adjust effects of early progression or death, in which patients who had events up to 2 months were excluded. Results: A total of 271 patients were included (median age, 70 [range 18–85] years; male/female, 64/36%; performance status (PS) 0/1/2, 47/49/4%; primary tumor site gastric/GEJ, 90/10%; status unresectable/recurrent, 81/19%; histology intestinal/diffuse, 30/70%; PD-L1 CPS <1/1~5/>5, 15/33/53%). Median follow-up time was 11.3 (range 1-30) months, and 80 (30%) patients developed irAE. In the landmark analysis, the median PFS was 11.1 months in the irAE group and 7.2 months in non-irAE group (HR 0.70 [95%CI 0.50-0.97], p = 0.034), and the median OS was 22.5 months in the irAE group and 17.9 months in non-irAE group (HR 0.77 [95%CI, 0.50-1.17], p = 0.219). The ORR were 67.4% in the irAE group and 66.7% in non-irAE group (p = 0.934). Multivariate analysis indicated that PS ≥1 (HR 1.66 [95%CI, 1.20-2.30], p = 0.02), elevated ALP (HR 1.61 [95%CI, 1.13-2.27], p = 0.008), and absence of irAEs (HR 1.55 [95%CI, 1.08-2.22], p = 0.018) were associated with poor prognosis. The most frequent irAEs were pneumonitis (n = 16), and grade ≥3 irAEs were observed in 26 (9.6%) patients: pneumonitis (n = 6), hepatitis/hypophysitis (n = 5). Conclusions: Development of irAEs was associated with improved outcomes in advanced gastric or GEJ cancer patients receiving first-line Nivo-CT.

Aspirin versus Clopidogrel monotherapy beyond 1 month after complex percutaneous coronary intervention: A pre-specified subgroup analysis of the STOPDAPT-3 trial.

There were no previous studies comparing aspirin versus P2Y12 inhibitor monotherapy following short dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI). We conducted a prespecified subgroup analysis based on complex PCI in the 1-year results of the STOPDAPT-3 trial, which randomly compared 1-month DAPT followed by aspirin monotherapy (aspirin group) to 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). The main analysis in the present study was the 30-day landmark analysis. The co-primary endpoints were cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) and major bleeding (Bleeding Academic Research Consortium 3 or 5). In the 30-day landmark analysis (N=5833), there were 1415 patients (24.3%) who underwent complex PCI. There was a significant interaction between complex PCI and the effect of aspirin group relative to clopidogrel group for cardiovascular events (complex PCI: 3.3% versus 5.2%, non-complex PCI, 4.3% versus 3.6%, interaction P=0.04) and net adverse clinical events (complex PCI: 4.8% versus 7.2%, non-complex PCI: 5.3% versus 4.4%, interaction P=0.02), but not for bleeding events (complex PCI: 2.1% versus 2.7%, non-complex PCI: 1.7% versus 1.4%, interaction P=0.35). There was a significant interaction between complex PCI and the effect of aspirin monotherapy relative to clopidogrel monotherapy beyond 1 month and up to 1 year for cardiovascular events due to numerically lower risk of aspirin monotherapy in patients with complex PCI, while the effect of aspirin monotherapy relative to clopidogrel monotherapy was not different for bleeding regardless of complex PCI. Clinical trial registration: ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111.

Tracking evolutionary changes within Allophaiomys, Terricola and Microtus voles revealed by a landmark point-based geometric morphometric study on molars from Hungary

ABSTRACT In the present work, a geometric morphologic study was carried out to compare the lower first molars of species belonging to the genera Allophaiomys, Terricola and Microtus and to explore the morphological variation within species. The examined teeth were recovered from nine Early and Middle Pleistocene sites, but recent material was also used in the study. We analysed the teeth of 733 Allophaiomys spp. 855 Terricola arvalidens, 339 Terricola hintoni and 625 recent Terricola subterraneus. Morphology and linear morphometric data of teeth were compared using canonical variate analysis and landmark analysis. The resulting morphological series reflect the phylogenetic relationships between species. We also tested the morphological changes observed in the fossil material with the separation times calculated from recent phylogenetic studies. Our results suggest that most phylogenetic changes can be traced by morphological analysis of this tooth. While the emergence of species belonging to the genera Terricola and Microtus is broadly consistent with the phylogenetic data, early colonisation of the genus Agricola was not morphologically detectable. The study of the genus Allophaiomys has revealed a palaeoecological difference between northern and southern Hungary during the mid-Pleistocene transition. Southern Hungary was covered with steppe, while northern Hungary was forested at that time.

Clinical significance of hyperuricaemia in biopsy-proven diabetic kidney disease ━ a single-centre retrospective study

AimsHyperuricaemia is associated with the development of Diabetic kidney disease (DKD). However, the mechanism of hyperuricaemia causing the progression of DKD remain unclear.MethodsThis is a single-centre retrospective study. 155 biopsy-proven DKD patients were grouped into hyperuricaemia and non-hyperuricaemia groups. Kaplan-Meier analysis and landmark curves were performed to explore predictors of end-stage renal disease (ESRD), Cox regression analysis was used to screen for factors, a nomogram was constructed to predict the renal prognosis of DKD.ResultsPatients in hyperuricaemia group had higher serum creatinine (Scr), degree of mesangial expansion and IFTA score and lower GFR, haemoglobin. SUA level was positively correlated with IFTA scores. The Kaplan-Meier curve and landmark analysis revealed worse survival in hyperuricaemia group, especially after 12 months. 11 variables, including age, sex, haemoglobin, Scr, SUA, and pathological score were collected to make a nomogram model. In the testing and training sets, the AUCs at 1, 3, and 5 years were 0.888, 0.939, and 0.886 and 0.947, 0.867, and 0.905, respectively.ConclusionThe clinicopathologic manifestation of DKD patients with hyperuricaemia was much more severe, and hyperuricaemia predicted a worse renal prognosis. A new renal prognosis prediction model including SUA was constructed for DKD with higher accuracy.

Comparison of short-and long-term outcomes between endovascular and open repair for descending thoracic aortic aneurysm: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate and compare the efficacy of endovascular versus open repair for the treatment of patients with descending thoracic aortic aneurysm (DTAA). A systematic search of the PubMed, Embase, and Cochrane Library databases for relevant studies was performed. Outcome data, including postoperative mortality and morbidity, operative details, all-cause survival, freedom from aortic-related survival and freedom from aortic-related re-intervention, were independently extracted by two authors in a standardized way. Twenty-nine studies comprising 49972 patients (22049 endovascular repair; 27923 open repair) were included. Endovascular repair was associated with a significantly lower postoperative mortality rate [odd ratio (OR): 0.57, 95% confidence interval (CI): 0.45-0.72; I2=72.58%] and morbidity. In terms of long-term survival, endovascular repair yielded better freedom from aortic-related survival [hazard ratio (HR): 0.71, 95% CI: 0.54-0.93, P =0.012] but inferior freedom from aortic-related reintervention (HR: 2.10, 95% CI: 1.45-3.04, P < 0.001). Landmark analysis revealed that the open repair group experienced better all-cause survival beyond 16months (HR: 1.64, 95% CI: 1.53-1.75, P < 0.001). In addition, in the subgroup of patients with intact DTAA, those who underwent open repair exhibited a higher rate of postoperative mortality (OR: 0.58, 95% CI: 0.38-0.88; I2=83.34%) but had better all-cause survival beyond 7months (HR: 1.72, 95% CI: 1.61-1.84, P < 0.001) than those who underwent endovascular repair. Among patients treated for DTAA, endovascular repair was associated with better freedom from aortic-related survival, a lower risk for postoperative mortality and morbidity, and shorter lengths of intervention, intensive care unit stay, and hospital stay than those who underwent open repair. Open repair yielded significantly better long-term all-cause survival and freedom from aortic-related re-intervention than endovascular repair.

Effects of Anticancer Therapy on Osteoporosis in Breast Cancer Patients: A Nationwide Study Using Data from the National Health Insurance Service-National Health Information Database

Background/Objectives: This nationwide retrospective study evaluated the effects of anticancer therapy on osteoporosis in 126,132 Korean breast cancer survivors from 2002 to 2020. Methods: The Cox proportional hazards model assessed the effects of treatment on osteoporosis. To circumvent the guarantee-time bias for osteoporosis development, a landmark analysis was employed. A stabilized inverse probability of treatment weighting was performed to control any confounding bias. The propensity score was calculated using a multinomial logistic regression model with age, national health insurance, and the Charlson comorbidity index. Results: During a median follow-up of 4.22 years, 28,603 cases of osteoporosis were documented. Aromatase inhibitors (AIs) were associated with a higher risk of osteoporosis development in comparison to tamoxifen (TMX) or chemotherapy. Notably, AIs administered subsequent to a combination of chemotherapy and anti-HER2 therapy exhibited the highest risk of osteoporosis development. Subgroup analysis revealed that the mean interval from breast cancer diagnosis to osteoporosis development was 5.00 years for women diagnosed with cancer at age &lt; 50 and 3.89 years for those diagnosed at age ≥ 60. TMX increased the risk of osteoporosis in women diagnosed with cancer at age &lt; 50, whereas chemotherapy was not a significant risk factor for osteoporosis development in those diagnosed at age ≥ 60. The impact of anticancer therapy on osteoporosis development was more pronounced in women diagnosed with breast cancer at a younger age compared to those diagnosed at an older age. Conclusions: Effective prevention and active management strategies should be implemented to address bone loss in both younger and older breast cancer patients.

P0694 Clinical response trajectories identify distinct subpopulations of ulcerative colitis patients and are linked to disease outcome across different therapy classes. Patient level analysis of 2378 participants from 6 randomized controlled trials in moderate-severe UC representing 8 different mechanisms of action.

Abstract Background In randomized placebo-controlled trials (RCTs) for ulcerative colitis (UC), remission rates below 40% (wk52). Landmark analyses using independent endpoints provide approvable estimands for overall efficacy but overlook individual variability.Notably, a subset of patients achieves deeper remission levels. Post hoc analysis of the SELECTION trial (filgotinib) demonstrated that treating daily PRO2 scores (stool frequency, rectal bleeding) as time-series data reveals discrete subpopulations.Patients with in the faster response trajectory groups achieve wk52 endpoints at higher rates including disease control. Methods In a cross-industry/academic collaboration, data from 2,378 UC responders from RCTs of adalimumab, brepocitinib, etrasimod, etrolizumab, ozanimod, ritlecitinib, ustekinumab, and vedolizumab in UC were analyzed for PRO2-based treatment response trajectories using Group-based trajectory modeling (GBTM). Using random-effects logistic regression, trajectory groups were linked to wk 12 and 52 outcomes, including comprehensive disease control (CDC), defined as achieving remission in endoscopy, symptoms, lab markers, and histology. Meta-analyses of baseline demographics/disease characteristics examined predictors of trajectory group affiliation and CDC at wk 52. Results GBTM identified 3–5 distinct response trajectories for each mechanism of action (MOA), ranging from super-fast responses to slow and incomplete responses or relapse, based on PRO2 dynamics. Meta-analysis revealed baseline factors associated with faster response, including prior biologic failure, lower endoscopic activity (Mayo-ES 2 vs. 3), lower Robarts Histology Index, lower baseline disease activity and male sex (0.78 [0.66, 0.93]) (Fig1). Across therapies, remission, mucosal healing, and comprehensive disease control (CDC) were most frequently achieved in fast and super-fast responders (15–37%), compared to slow or non-responders (2.6–8.1%). Random-effects logistic regression confirmed better clinical outcomes for faster responders (Tab1). Conclusion Distinct subgroups (response trajectories) with specific PRO2-based response dynamics were consistently identified. In all trials, patients with (super)fast responses had significantly higher odds of achieving mucosal healing, deep remission, and comprehensive disease control (CDC) at wk52. While some baseline characteristics were linked to faster responses, they only partially account for the observed separation of patient groups. Response trajectories likely reflect underlying heterogeneity in disease biology in the interaction with the different MOA (i.e. endotypes). RNASeq analysis of transcriptome regulation in these patients aims to further explore this hypothesis. References Schreiber S et al. UEG Journal, doi:10.1002/ueg2.12686

Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial.

The multicenter, phase III GMMG ReLApsE trial (EudraCT-No:2009-013856-61) randomized relapsed and/or refractory multiple myeloma (RRMM) patients equally to lenalidomide/dexamethasone (LEN/DEX, 25mg days 1-21/40mg weekly, 4-week cycles) re-induction, salvage high dose chemotherapy (sHDCT, melphalan 200mg/m2), autologous stem cell transplantation (ASCT) and LEN maintenance (10mg/day; transplant arm, n=139) versus continuous LEN/DEX (control arm, n=138). Ninety-four percent of patients had received frontline HDCT/ASCT. We report an updated analysis of survival endpoints with a median follow-up of 99 months. Median progression-free survival (PFS) was 20.5 and 19.3 months in the transplant and control arm, respectively (HR 0.98; 95% CI 0.76-1.27; p=0.9). Median overall survival (OS) was 67.1 and 62.7 months (HR 0.89; 95% CI 0.66-1.20; p=0.44). Landmark analyses from sHDCT and the contemporaneous LEN/DEX cycle 5 were performed due to dropout of 29% of patients before sHDCT/ASCT in the transplant arm but did not reveal significant differences in PFS (23.0 vs. 20.3 months; HR 0.91; 95% CI 0.68-1.22; p=0.52) or OS (76.3 vs. 66.0 months; HR 0.8; 95% CI 0.56-1.13; p=0.2). Time to progression after frontline HDCT/ASCT (TTP1) was a prognostic factor but did not predict benefit from sHDCT/ASCT. The GMMG ReLApsE trial does not support use of sHDCT/ASCT in RRMM after frontline HDCT/ASCT. EudraCT-No: 2009-013856-61.

Association of varicose veins with the risk of heart failure: A nationwide cohort study.

Research investigating the association between varicose veins (VV) and heart failure has been limited. Here, we examine this association within a nationwide longitudinal cohort, hypothesizing an increased risk of heart failure associated with the presence of VV. Our study included 390,436 participants based on health screening results conducted from 2005 to 2010 in the South Korean health screening cohort database. Presence of VV was defined as having at least two claims based on International Classification of Diseases, Tenth Revision (ICD-10) codes I830-832, I839, or I868. Propensity score matching (PSM) at a ratio of 1:5 was employed to categorize the participants into two groups based on the presence of VV. The primary outcome, heart failure incidence, was defined as two or more claims with ICD-10 code I50 during follow-up. Among the participants, presence of VV was noted in 5,008 (1.28%) individuals. Over a median follow-up period of 13.33 years (interquartile range 10.4-16.26), 55,023 cases of heart failure (14.0%) occurred. In the multivariable analysis, the group with VV consistently showed an increased incidence risk of heart failure compared to the group without VV, both before (hazard ratios [HR], 1.174; 95% confidence interval [CI], 1.089-1.265) and after PSM (HR, 1.171; 95% CI, 1.070-1.283). Landmark analysis also found a consistent relationship between the presence of VV and the incidence risk of heart failure before (HR, 1.190; 95% CI, 1.103-1.285) and after PSM (HR, 1.144; 95% CI, 1.044-1.254). This study revealed a significant increase in the risk of heart failure among patients with VV in the general population of South Korea. Given that the presence of VV is likely associated with an increased risk of heart failure in the general population, the potential for future heart failure should be taken into consideration when VV are present.

Sex differences in the risk of bladder cancer among kidney transplant recipients and patients with kidney failure receiving hemodialysis: a nationwide cohort study.

Although both patients with kidney failure (KF) receiving hemodialysis (HD) and kidney transplant (KT) recipients (KTRs) have a high risk of bladder cancer, how this risk changes in the transition from dialysis to KT is unknown. In this study, we aimed to investigate the risk of bladder cancer in KTRs and patients on HD. This was a nationwide longitudinal cohort study of 66,547 participants from the National Health Insurance Service cohort who started HD for KF or received KT from 2002 to 2020. The primary outcome was the diagnosis of bladder cancer, which was defined as the composite of diagnostic codes and either hospitalization or ≥2 outpatient visits for bladder cancer. During mean follow-ups of 4.2 and 7.9 years in the HD and KT groups, respectively, the incidence rates of bladder cancer were 1.1/1,000 and 0.3/1,000 person-years, respectively. In the time-dependent multivariable Cox models, compared to patients on HD, the adjusted hazard ratio (aHR) for bladder cancer among KTRs was 0.36 (95% confidence interval [CI], 0.21-0.60; p<0.001). Among men, this aHR was 0.29 (95% CI, 0.15-0.55; p<0.001); however, no statistically significant association between the kidney replacement therapy modality and the risk of bladder cancer was observed among women. Landmark analysis performed to avoid immortal time bias by redefining time zero as a specific landmark time (2 and 5 years after HD initiation or KT) revealed similar results. The risk of bladder cancer was significantly lower among KTRs than that among patients receiving HD, particularly among men.

Concomitant Usage of H1-Antihistamines and Immune Checkpoint Inhibitors on Cancer Patient Survival.

Recent research (Li etal. 2021) suggests an upregulated expression and activation of H1 receptors on macrophages in the tumor microenvironment, and concomitant H1-antihistamine use is associated with improved overall survival in patients with lung and skin cancers receiving immunotherapy. Therefore, we retrospectively evaluated the impacts of H1-antihistamine use in cancer patients during immunotherapy. All patients who had received at least one dose of immune checkpoint inhibitors (ICIs) from July 1, 2014 to October 31, 2019 were identified from Hong Kong's territory-wide database, with this date defined as the baseline. A 1-month landmark analysis was conducted with follow-for up to 6 months, including an exposure period of 1 month before and after the baseline date. Patients were grouped according to the types of primary cancer and the percentages of daily H1-antihistamine usage within the exposure period. The primary outcome was overall survival. A total of 1740 (65.1% male, mean age 61.9 years) were included in the landmark analysis, of which 529 (30.4%) and 307 (17.6%) had primary lung and liver malignancies. The multivariable Cox regression model estimated statistically significant improvement in overall survival of intermediate use in patients with primary lung malignancies (adjusted hazard ratio [aHR] 0.223, 95% confidence interval [CI] 0.052-0.958, p = 0.044), but not with primary liver maligancies. Similar frequency-dependent effects were identified in Kaplan-Meier analysis. The benefits of adjunctive use of H1-antihistamines may be generation- and tumor-dependent. Further clinical and mechanistic studies are required to confirm the findings.

Long-term outcome for neoadjuvant versus adjuvant chemotherapy in early breast cancer and the prognostic impact of nodal therapy response: A population-based study.

Although neoadjuvant systemic treatment for non-metastatic breast cancer has gained ground during the past decade, there is no compelling evidence that it improves overall survival compared to primary tumor resection and adjuvant treatment. At the same time, the approach to responders to neoadjuvant treatment in the axilla is evolving. This is a retrospective analysis of a prospectively collected population-based registry. Patients that received neoadjuvant (n=2126) or adjuvant chemotherapy (n=4754) for non-metastatic breast cancer during 2007-2020 in the Stockholm-Gotland region, which comprises 25% of the entire Swedish population, were included. Overall survival of patients treated preoperatively and postoperatively was compared using inverse probability treatment weighting and landmark analysis. The prognostic impact of change between prechemotherapy clinical to postchemotherapy pathologic nodal stage (cN/pN) in women receiving neoadjuvant treatment was investigated. Median follow-up was 4.93 years. There was no difference in adjusted overall survival between adjuvant (reference) and neoadjuvant treatment in the entire population (HR=1.38, 95% CI 0.98-1.93, p=0.062) or in breast cancer subtypes. Patients converting from positive clinical to negative pathologic nodal stage (cN+/pN0) had improved outcomes compared to cN0/pN0 or patients with pN0 following primary surgery. These patients had a particular disease trajectory, with early peak in risk of death followed by quick and sustained decrease. There was no difference in survival of patients treated with neoadjuvant versus adjuvant systemic therapy for non-metastatic breast cancer. Patients with cN+/pN0 have excellent prognosis and represent potential candidates for de-escalation of local and systemic treatment.

Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.

Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T. Three key IR criteria were defined as CD4+ T helper (TH) cells > 200/µL, any detectable B cells, and serum immunoglobulin G (IgG) levels >4 g/L. After a median follow-up of 24.6 months, 38% of patients displayed TH cells, 11% showed any B cells, and 41% had IgG recovery. Notable product-specific differences emerged, including deeper TH cell aplasia with CD28z- versus longer B-cell aplasia with 41BBz-based products. Patients with any IR recovery experienced extended progression-free survival (PFS) (median 20.8 vs. 1.7 months, p < 0.0001) and overall survival (OS) (34.9 vs. 4.0 months, p < 0.0001). While landmark analysis at 90 days confirmed improved PFS in patients with any recovery (34.9 vs. 8.6 months, p = 0.005), no significant OS difference was noted. Notably, 72% of patients with refractory disease never displayed recovery of any IR criteria. Early progressors showed diminished IR at the time of progression/relapse compared to patients with late progression/recurrence (after Day 90). Our results highlight the profound immune deficits observed after CD19 CAR-T and shed light on the intersection of IR and efficacy in B-NHL. Importantly, IR was impaired considerably postprogression, carrying significant implications for subsequent T-cell-engaging therapies and treatment sequencing.

Prevalence of complications of buccal fat removal: A systematic review and meta-analysis.

Removal of the buccal fat pad can be considered safe as long as there is a detailed analysis of anatomical landmarks. The objective of this study was to estimate the prevalence of intra- and postoperative complications resulting from buccal fat pad removal through a systematic review. The search strategy involved observational and/or interventional studies in humans that included at least one case of buccal fat pad removal with a description of the surgery, postoperative progress, and complications. Methodological quality assessment was performed using the JBI checklist. Study heterogeneity was assessed using the I2 test. In total, 12 studies were included. Out of 308 patients who underwent buccal fat pad removal, 81 experienced some form of complication, with an overall prevalence of 25% (95% CI=0.04-0.46). Complications found in the data collection included edema (38.40%), trismus (30.09%), pain (19.41%), asymmetry (11.65%), facial nerve paralysis (0.97%), infection (0.48%), hematoma (0.48%), and unilateral emphysema (0.48%). All complications occurred in the postoperative period. There was high heterogeneity among the studies. One in four patients undergoing buccal fat pad removal experiences some form of postoperative complication. Consequently, the procedure should be recommended with caution because there is evidence for safety concerns and a lack of predictability in the evaluated studies.

Accuracy of cephalometric landmark and cephalometric analysis from lateral facial photograph by using CNN-based algorithm

Cephalometric analysis is the primary diagnosis method in orthodontics. In our previous study, the algorithm was developed to estimate cephalometric landmarks from lateral facial photographs of patients with normal occlusion. This study evaluates the estimation accuracy by the algorithm trained on a dataset of 2320 patients with added malocclusion patients and the analysis values. The landmarks were estimated from the input of lateral facial photographs as training data using trained CNN-based algorithms. The success detection rate (SDR) was calculated based on the mean radial error (MRE) of the distance between the estimated and actual coordinates. Furthermore, the estimated landmarks were used to measure angles and distances as a cephalometric analysis. In the skeletal Class II malocclusion, MRE was 0.42 ± 0.15 mm, and in the skeletal Class III malocclusion, MRE was 0.46 ± 0.16 mm. We conducted a cephalometric analysis using the estimated landmarks and examined the differences with actual data. In both groups, no significant differences were observed for any of the data. Our new algorithm for estimating the landmarks from lateral facial photographs of malocclusion patients resulted in an error of less than 0.5 mm; the error in cephalometric analysis was less than 0.5°. Therefore, the algorithm can be clinically valuable.

Consolidation With Second High Dose Therapy and Autologous Stem Cell Transplantation Is Associated With Improved Overall Survival in Patients With Multiple Myeloma in First Relapse.

High dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) remains the preferred first line consolidation strategy for newly diagnosed multiple myeloma (MM). However, The role of HDT/ASCT in first relapse is uncertain in the context of novel therapies. This study evaluates real-world outcomes of MM patients in first relapse, focusing on the role of consolidative HDT/ASCT. This retrospective cohort study was conducted at a large tertiary referral center in Northern Netherlands. MM patients who received first-line HDT/ASCT and obtained a good response were included. The time to next treatment or death (TTNT-D 2) and overall survival (OS) were evaluated, while identifying prognostic factors. A landmark analysis was performed at 6 months, including only patients with a partial response (PR) or better after re-induction. This study identified 237 patients potentially eligible for repeated HDT/ASCT of whom 111 (47%) underwent a second consolidative HDT/ASCT. The median follow-up is 40 months. Baseline characteristics were largely similar, though second HDT/ASCT was applied only after achieving PR or better. In the landmark analysis, absence of high-risk cytogenetics and good performance status were associated with longer TTNT-D 2. Consolidative second HDT/ASCT, absence of high-risk cytogenetics and longer first response duration were associated with longer OS. Transplantation-related mortality rate was < 1%. This study highlights the viability of second HDT/ASCT as treatment option for relapsed MM, particularly for patients with good responses to first-line HDT/ASCT. In the era of novel agents, second HDT/ASCT should be considered a feasible and effective consolidative strategy.

Evaluation of nasal septum deviation via reformatted computed tomography (CT) imaging following expansion using RPE and MARPE.

To evaluate whether rapid palatal expansion (RPE) or miniscrew-assisted rapid palatal expansion (MARPE) affects nasal septum deviation (NSD). The study population includes 22 RPE patients ages 9.62 ± 1.38 years and 20 MARPE patients ages 19.38 ± 7.82 years with initial diagnostic cone-beam computed tomography (CBCT) scans (T0). Another CBCT scan (T1) was taken after patients underwent RPE or MARPE expansion treatment alone. NSD was evaluated three-dimensionally using a custom landmark analysis on T0 and T1 CBCT scans. Principal component analysis (PCA) and canonical variate analysis (CVA) were used to identify nasal septum shape differences before and after expansion treatment. PCA and CVA showed that while there was change in nasal septum shape from T0 to T1 for MARPE and RPE treatments, the general pattern in morphological change was not found when comparing the variety of phenotypes between individuals. The Procrustes ANOVA regression found P-values for MARPE centroid size and shape were 0.7861 and 1, and RPE centroid size and shape were 0.3508 and 1, respectively, suggesting that there were no significant differences in nasal septum size and shape following expansion. CVA found P-values were 0.99 for MARPE and 0.99 for RPE after 10,000 permutation tests for Procrustes distances, indicating that there were no significant differences between T0 and T1 group means for both treatment groups. MARPE and RPE expansion treatments had no effect on nasal septum deviation from T0 to T1.

Allogeneic stem cell transplantation against aggressive lymphomas: graft-versus-lymphoma effects in peripheral T-cell lymphoma and diffuse large B-cell lymphoma after myeloablative conditioning

Allogeneic stem cell transplantation (alloSCT) represents a curative option for patients with relapsed/refractory (r/r) aggressive lymphomas. We compared outcomes of alloSCT in r/r PTCL and r/r DLBCL pts (n = 150) who underwent identical myeloablative conditioning chemotherapy, GvHD prophylaxis, and relapse management. 5-year PFS and OS were significantly superior in PTCL compared to DLBCL (56% vs. 24%; 56% vs. 28%; p ≤ 0.005). A landmark analysis (day≥ +100 post-alloSCT) markedly favored outcomes in PTCL vs. DLBCL: 5-year PFS and OS of 76% vs. 30% and 76% and 35%, respectively (p ≤ 0.003). Non-relapse mortality was comparable (35% PTCL vs. 34% DLBCL, p = 0.894), whereas post-alloSCT relapse mortality was significantly higher in DLBCL (36% vs. 10%, p = 0.0007). The occurence of limited chronic GvHD did not improve outcomes in DLBCL, whereas extensive chronic GvHD was a negative risk factor for both (HR 2.09 and 2.80, p ≤ 0.006). In conclusion, we gained evidence for strong graft-versus-lymphoma activity against PTCL but not DLBCL.

Frequency and Significance of Body Weight Loss During Immunochemotherapy in Patients with Advanced Non-Small Cell Lung Cancer.

Background: Limited data are available on the frequency and significance of body weight loss during cancer therapy. This study investigated the frequency of patients who experienced body weight loss during immune checkpoint inhibitor (ICI) plus chemotherapy for advanced non-small cell lung cancer (NSCLC) and the impact of weight loss on treatment outcomes. Methods: Using the clinical data of 370 patients with NSCLC who received a combination of ICI and chemotherapy at 13 institutions, this study investigated the frequency of body weight loss > 5% during treatment and determined the impact of body weight loss on patient outcomes. Results: Of the 370 included patients, 141 (38.1%) lost more than 5% of their body weight during ICI plus chemotherapy (WL group). The 2-month landmark analysis showed that patients who experienced body weight loss of >5% during treatment had worse overall survival (OS) and progression-free survival (PFS) than those who did not (OS 14.0 and 31.1 months in the WL non-WL groups, respectively, p < 0.001; PFS 6.8 and 10.9 months in the WL non-WL groups, respectively, p = 0.002). Furthermore, a negative impact of body weight loss on survival was observed even in those who had obesity (body mass index [BMI] ≥ 25.0) at the start of therapy (OS 12.8 and 25.4 months in the WL non-WL groups, respectively, p < 0.001; PFS 5.7 and 10.7 months in the WL non-WL groups, respectively, p = 0.038). Conclusions: In conclusion, weight loss of >5% during ICI plus chemotherapy negatively influenced patient outcomes. Further and broader studies should investigate the role of nutritional status, specifically weight change and nutritional support, in responsiveness to ICI plus chemotherapy.

Combining moderate dosage of Bevacizumab with TAS-102 provides longer progression-free time in refractory metastatic colorectal Cancer

PurposeWe aimed to evaluate the efficacy of moderate doses of bevacizumab in combination with TAS-102 for the treatment of refractory metastatic colorectal cancer.MethodsA total of 261 patients with refractory mCRC were enrolled and categorized into two groups: TAS-102 combined with bevacizumab and TAS-102 alone. Patients in the bevacizumab combination group were divided into two subgroups based on a median dose of 3.3 mg/kg. Categorical variables were compared using the chi-square or Fisher’s exact test, and continuous variables were assessed using the t-test. The Cox proportional hazards model was used to adjust covariates. Survival analysis was performed using the log-rank test and Kaplan–Meier curves. Specific survival was evaluated using restricted mean survival time (RMST) and landmark analysis.ResultThe median progression-free survival (PFS) was 3.7 months in the TAS-102 combined with the bevacizumab group and 2.2 months in the non-bevacizumab group, showing significance in favor of the bevacizumab combination. Median overall survival (OS) was 9.4 months in the bevacizumab combination group and 10.3 months in the group that did not receive combination therapy. A survival benefit was observed within 9.5 months in both the RMST and landmark analyses. The PFS benefit was consistent across different doses of bevacizumab, while no significant difference in OS was observed compared to TAS-102 monotherapy. Both PFS and OS did not significantly differ between the different doses of bevacizumab.ConclusionModerate doses of bevacizumab and TAS-102 provided satisfactory efficacy over the standard dose within a limited timeframe of 9.5 months.