Cox Proportional Hazards Regression Survival Research Articles

Obinutuzumab versus rituximab for the treatment of refractory primary membranous nephropathy.

Rituximab has been shown effective in patients with primary membranous nephropathy refractory to glucocorticoids plus cyclophosphamide (GC+CTX) or calcineurin inhibitors (CNIs), but the response rates remain limited. Compared with rituximab, obinutuzumab is a humanized anti-CD20 monoclonal antibody with greater B-cell depletion capacity. This study was performed to investigate the effectiveness of obinutuzumab compared to rituximab in treating patients with refractory primary membranous nephropathy. A retrospective study was conducted at Huashan Hospital, Fudan University between January 1, 2015 and July 31, 2024, and included adult patients with primary membranous nephropathy who met the following criteria, 1) resistance to GC+CTX and/or calcineurin inhibitor (CNI) regimens, 2) dependence on CNIs, or 3) relapse within 1 year after CTX discontinuation. The patients subsequently received either obinutuzumab or rituximab. The primary endpoint was treatment response, which was defined as overall remission of nephrotic syndrome with no need for rescue therapy after obinutuzumab versus rituximab treatment. The secondary measures included immunological remission and safety profiles. Among the 51 participants, 20 received obinutuzumab and 31 received rituximab. The response rate was significantly greater in patients receiving obinutuzumab than in those receiving patients (90.0% vs. 38.7%, p<0.001) during a follow-up period of 24 (IQR, 10-34) months. Cox proportional hazards survival regression analysis also revealed the superior effectiveness of obinutuzumab (p<0.001). Immunological remission rates were higher in patients receiving obinutuzumab at both 3 months (75.0% vs. 20.0%, p<0.001) and 6 months (87.5% vs. 21.4%, p<0.001). The safety profiles of the two treatments were comparable. Among the 19 nonresponders treated with rituximab, 10 subsequently received obinutuzumab, and 8 achieved remission during a follow-up period of 20.0 (IQR, 18.5-22.3) months. This retrospective study suggests that obinutuzumab is an effective treatment option for patients with primary membranous nephropathy refractory to GC+CTX, CNI, and rituximab regimens.

Impact of the Preservation of Residual Kidney Function on Hemodialysis Survival: Results from the BISTRO Trial.

Preservation of residual kidney function (RKF) in dialysis patients has been associated with improved survival. RKF in the BISTRO trial was relatively well preserved and here we describe its association with survival during the trial and extended follow-up. RKF, measured as the average urea and creatinine clearance (GFR) or 24-hour urine volume was assessed at baseline, one, two and three months and three-monthly up to 2 years in incident haemodialysis patients. Time to event survival data or competing events (transplantation, modality change) were obtained for 50 months post enrolment via data linkage with the UK Renal Registry. Cox proportional hazards regression survival models, including those incorporating change in GFR from baseline as a time-varying variable and joint regression models for longitudinal and survival data (longitudinal models for GFR or urine volume) were used to explore the relationship of RKF preservation with survival. Analyses were adjusted for age, sex, comorbidity and ethnicity. 2919 measures of RKF were made in 387 patients from 32 UK dialysis units. Higher age and comorbidity score associated with increased mortality in all models. Baseline GFR reduced the risk of death (Hazard Ratio: 0.918 95%CI: 0.844, 0.999) per ml/min/1.73m2. A greater fall in GFR and urine volume from baseline was associated with a non-significant increased risk of death as visualised on spline plots. In the joint survival models higher GFR (adjusted HR: 0.88 95%CI 0.80, 0.97) or urine volume (adjusted HR: 0.75 95%CI 0.57, 0.95 per L) at any time point associated with better survival. Lower RKF during the first two years of haemodialysis is associated with an increased death risk for up to 50 months following dialysis initiation. This adds to a growing body of evidence that interventions to preserve RKF should be developed and tested in clinical trials.

GLP1R Gene Expression and Kidney Disease Progression

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have nephroprotective properties beyond those related to weight loss and glycemic control. To investigate the association of genetically proxied GLP-1RAs with kidney disease progression. This genetic association study assembled a national retrospective cohort of veterans aged 18 years or older from the US Department of Veterans Affairs Million Veteran Program between January 10, 2011, and December 31, 2021. Data were analyzed from November 2023 to February 2024. Genetic risk score for systemic GLP1R gene expression that was calculated for each study participant based on genetic variants associated with GLP1R mRNA levels across all tissue samples within the Genotype-Tissue Expression project. The primary composite outcome was incident end-stage kidney disease or a 40% decline in estimated glomerular filtration rate. Cox proportional hazards regression survival analysis assessed the association between genetically proxied GLP-1RAs and kidney disease progression. Among 353 153 individuals (92.5% men), median age was 66 years (IQR, 58.0-72.0 years) and median follow-up was 5.1 years (IQR, 3.1-7.2 years). Overall, 25.7% had diabetes, and 45.0% had obesity. A total of 4.6% experienced kidney disease progression. Overall, higher genetic GLP1R gene expression was associated with a lower risk of kidney disease progression in the unadjusted model (hazard ratio [HR], 0.96; 95% CI, 0.92-0.99; P = .02) and in the fully adjusted model accounting for baseline patient characteristics, body mass index, and the presence or absence of diabetes (HR, 0.96; 95% CI, 0.92-1.00; P = .04). The results were similar in sensitivity analyses stratified by diabetes or obesity status. In this genetic association study, higher GLP1R gene expression was associated with a small reduction in risk of kidney disease progression. These findings support pleiotropic nephroprotective mechanisms of GLP-1RAs independent of their effects on body weight and glycemic control.

Prognostic model development for risk of curve progression in adolescent idiopathic scoliosis: a prospective cohort study of 127 patients.

The study's purpose was to develop and internally validate a prognostic survival model exploring baseline variables for adolescent idiopathic scoliosis curve progression. A longitudinal prognostic cohort analysis was performed on trial data (n = 135) including girls and boys, Cobb angle 25-40°, aged 9-17 years, remaining growth > 1 year, and previously untreated. Prognostic outcome was defined as curve progression of Cobb angle of > 6° prior to skeletal maturity. 34 candidate prognostic variables were tested. Time-to-event was measured with 6-month intervals. Cox proportional hazards regression survival model (CoxPH) was used for model development and validation in comparison with machine learning models (66.6/33.3 train/test data set). The models were adjusted for treatment exposure. The final primary prognostic model included 127 patients, predicting progress with acceptable discriminative ability (concordance = 0.79, 95% confidence interval [CI] 0.72-0.86). Significant prognostic risk factors were Risser stage of 0 (HR 4.6, CI 2.1-10.1, P < 0.001), larger major curve Cobb angle (HRstandardized1.5, CI 1.1-2.0, P = 0.005), and higher score on patient-reported pictorial Spinal Appearance Questionnaire (pSAQ) (HRstandardized 1.4, CI 1.0-1.9, P = 0.04). Treatment exposure, entered as a covariate adjustment, contributed significantly to the final model (HR 3.1, CI 1.5-6.0, P = 0.001). Sensitivity analysis displayed that CoxPH maintained acceptable discriminative ability (AUC 0.79, CI 0.65-0.93) in comparison with machine learning algorithms. The prognostic model (Risser stage, Cobb angle, pSAQ, and menarche) predicted curve progression of > 6° Cobb angle with acceptable discriminative ability. Adding patient report of the pSAQ may be of clinical importance for the prognosis of curve progression.

Patient- vs Physician-Initiated Response to Symptom Monitoring and Health-Related Quality of Life

Online symptom monitoring through patient-reported outcomes can enhance health-related quality of life and survival. However, widespread adoption in clinical care remains limited due to various barriers including the need to reduce health care practitioners' workload. To report the effects of patient-reported outcome (PRO) symptom monitoring on HRQOL and survival up to 1 year after initiation of any treatment in patients with lung cancer. SYMPRO-Lung is a multicenter stepped-wedge cluster randomized trial including patients with stage I to IV lung cancer. The inclusion period was from October 24, 2019, until September 16, 2021, and data collection ended October 8, 2022. Data analysis was conducted from November 9, 2023, until March 18, 2024. Patients in the intervention group reported PRO symptoms weekly using the Patient Reported Outcomes version of the Common Toxicity Criteria for Adverse Events lung cancer subset. If symptoms exceeded a validated threshold, an alert was sent to the health care practitioner (active intervention subgroup) or to the patient (reactive intervention subgroup). Patients in the control group received standard care. Health-related quality of life was measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire at baseline, 15 weeks (T1), 6 months (T2), and 1 year (T3), with the summary score (SS) and physical functioning (PF) as primary end points. Linear mixed-effects modeling was used to assess mean differences over time. Effect size (ES) of 0.40 or greater was considered clinically relevant. Cox proportional hazards regression survival analyses were performed to estimate the effect of the intervention on progression-free survival and overall survival (OS). Data were analyzed on an intention-to-treat basis. A total of 515 patients (266 [51.7%] men; mean [SD] age, 65.4 [9.4] years) were included in the study (266 in the control group; 249 in the pooled intervention group). Most baseline characteristics were balanced between groups; however, the most notable exception was the distribution in cancer staging: the intervention group had a higher proportion of patients with stage IV cancer compared with the control group (139 [56%] vs 118 [44%]). The pooled intervention group had a significantly better SS (mean difference T1, 5.22; 95% CI, 2.72-7.73; P < .001; ES = 0.33; mean difference T2, 6.28; 95% CI, 3.65-8.92; P < .001; ES = 0.40; mean difference T3, 3.97; 95% CI, 1.15-6.80; P = .006; ES = 0.25) compared with the control group. Group differences improved more in PF but did not meet the ES greater than or equal to 0.40 threshold (mean difference T1, 7.00; 95% CI, 3.65-10.35; P < .001; ES = 0.27; mean difference T2, 6.79; 95% CI, 3.26-10.31; P < .001; ES = 0.26; mean difference T3, 5.01; 95% CI, 1.23-8.79; P = .009; ES = 0.19). No significant differences in HRQOL were observed between the reactive (n = 89) and active (n = 160) intervention groups. The HR for progression-free survival for the active intervention group compared with the control group was 0.78 (95% CI, 0.58-1.04); the finding was not statistically significant. The HR for overall survival for both interventions groups compared with the control group were not statistically significant.(active: HR, 0.80; 95% CI, 0.55-1.15; reactive: HR, 0.69; 95% CI, 0.42-1.15). In this 1-year follow-up of a stepped-wedge cluster randomized trial, PRO symptom monitoring yielded improvements in long-term HRQOL in patients with lung cancer. The reactive approach proved equally effective as the active approach. A nonsignificant potential survival benefit was observed for the intervention group. These positive results provide further evidence for the usefulness of routine PRO symptom monitoring in lung cancer care. The Netherlands trial register Identifier: NL7897.

Prognostic Factors and Survival Outcomes in Squamous Cell Carcinoma of the Thyroid: A Surveillance, Epidemiology, and End Results (SEER) Database Analysis.

Introduction Squamous cell carcinoma of the thyroid (SCCT) is a rare, aggressive thyroid cancer distinguished by the emergence of squamous cells due to chronic inflammation or metaplasia. It poses diagnostic and therapeutic challenges, often identified at an advanced stage with a poor prognosis. The rarity of SCCT underscores the necessity for advanced research on effective treatments and diagnostic strategies. The current data utilized the Surveillance, Epidemiology, and End Results (SEER) database to determine the characteristics and outcomes of patients with primary SCCT. Methods De-identified data from patients with primary SCCT from 2000 to 2020 were collected using the SEER database. Demographic data, including age, sex, race, income, and housing, and clinical data including tumor size, tumor stage, nodal status, metastases, treatment modality, survival, and the patient's status, were extracted. Exclusion criteria were patients with unknown outcomes and missing death certificates. A detailed comparison of the two patient cohorts and univariate and multivariate Cox proportional hazard regression survival analyses were conducted. Results Among the 159 primary SCCT patients, the median age was 71 ± 21 years, with 83 females (52.2%) and 76 males (47.8%). The median overall follow-up was 6.0 years (4.41-7.59). The majority were White (108, 67.9%), followed by Hispanic (19, 11.9%). The five-year overall survival (OS) of the study group was 17.6% (95% CI = 14.5-20.7). The five-year disease-specific survival (DSS) was 37.6% (95% CI = 32.7-42.5). There was no significant difference based on surgery, chemotherapy, or radiation (p = 0.134). Age, tumor stage, nodal status, and distant metastases were negative prognostic factors. Sex, race, income, and housing were not predictive of survival. Conclusion The current study on SCCT highlights a low five-year OS rate of 17.6% and a DSS rate of 37.6%, with no significant difference in survival based on surgery, chemotherapy, or radiation. The negative prognostic factors included age, tumor stage, nodal status, and distant metastases, whereas sex, race, income, and housing did not significantly predict survival outcomes. These findings underscore the critical need for early detection and the development of more effective treatment strategies to manage SCCT.

Vaccine effectiveness against hospitalisation estimated using a test-negative case-control study design, and comparative odds of hospital admission and severe outcomes with COVID-19 sub-lineages BQ.1, CH.1.1. and XBB.1.5 in England.

Since the first emergence of Omicron BA.1 in England in November 2021, numerous sub-lineages have evolved. In September 2022, BA.5 dominated. The prevalence of BQ.1 increased from October, while the prevalence of CH.1.1 and XBB.1.5 increased from December 2022 and January 2023, respectively. Little is known about the effectiveness of the vaccines against hospitalisation with these sub-lineages, nor the relative severity, so we here used national-level electronic health records from England to estimate vaccine effectiveness and variant severity. The study period for tests contributing to all analyses was from 5th December 2022 to 2nd April 2023, when the variants of interest were co-circulating. A test-negative case-control study was used to estimate the incremental effectiveness of the bivalent BA.1 booster vaccines against hospitalisation, relative to those with waned immunity where the last dose was at least 6 months prior. The odds of hospital admission for those testing PCR positive on the day of an attendance to accident and emergency departments and the odds of intensive care unit admission or death amongst COVID-19 admissions were compared between variants. Additionally, a Cox proportional hazards survival regression was used to investigate length of stay amongst hospitalised cases by variant. Our vaccine effectiveness study included 191,229 eligible tests with 1647 BQ.1 cases, 877 CH.1.1 cases, 1357 XBB.1.5 cases and 187,348 test negative controls. There was no difference in incremental vaccine effectiveness against hospitalisation with BQ.1, CH.1.1 or XBB.1.5, nor was there a difference in the severity of these variants. Effectiveness against hospitalisation was 48.0% (95% C.I.; 38.5-56.0%), 29.7% (95% C.I.; 7.5-46.6%) and 52.7% (95% C.I.; 24.6-70.4%) against BQ.1, CH.1.1 and XBB.1.5, respectively, at 5-9 weeks post booster vaccination. Compared to BQ.1, the odds of hospital admission were 0.87 (95% C.I.; 0.77-0.99) and 0.88 (95% C.I.; 0.75-1.02) for CH.1.1 and XBB.1.5 cases attending accident and emergency departments, respectively. There was no significant difference in the odds of admission to intensive care units or death for those with CH.1.1 (OR 0.96, 95% C.I.; 0.71-1.30) or XBB.1.5 (OR 0.67, 95% C.I.; 0.44-1.02) compared to BQ.1. There was also no significant difference in the length of hospital stay by variant. Together, these results provide reassuring evidence that the bivalent BA.1 booster vaccines provide similar protection against hospitalisation with BQ.1, CH.1.1 and XBB.1.5, and that the emergent CH.1.1 and XBB.1.5 sub-lineages do not cause more severe disease than BQ.1. None.

Survival Outcomes of Patients with Diffuse Large B-Cell Lymphoma Who Received Autologous Stem Cell Transplantation in Germany - Real World Evidence from an Administrative Database

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma with increasing incidence. Autologous stem cell transplantation (ASCT) is a treatment option for patients who relapse or progress after up-front chemoimmunotherapy if they suitable for ASCT. However, patients may not qualify for this treatment because of age and/or comorbidity or because they are non-responder to second-line chemoimmunotherapy. Limited real-world data of the ASCT patient population is available for Germany. Therefore, this retrospective database analysis was conducted to describe real-world survival outcomes of patients with DLBCL who received ASCT in Germany. Patients and Methods: Using a large claims database of the German statutory health insurance with 6.7 million enrollees between 2010 and 2019, we identified patients who were newly diagnosed with DLBCL, had no other cancer co-morbidity, and received ASCT (index date). Pre-defined treatment lines were used to identify the utilization of ASCT. Unadjusted overall survival (OS) from index was plotted by means of the Kaplan-Meier estimator for the overall population and for those patients who had/had not a subsequent treatment line after ASCT. Furthermore, we performed a Cox proportional hazard survival regression with the following co-variates: age, sex, Charlson Comorbidity Index (CCI), time from start of first line treatment to ASCT, and presence of subsequent treatment after ASCT. Results: 112patients received ASCT. Among them, 39.3% received subsequent treatment after ASCT. Time to ASCT was on average 11.7 months for the entire cohort. Median OS estimated by Kaplan-Meier was 83.4 months for the entire cohort and 27.8 months for patients who received subsequent treatment. Median OS was not estimated for the group without subsequent treatment, for whom the Kaplan-Meier curve reached a plateau at just under 90%, assuming a potential cure. Finally, the only variable significantly reducing the OS was the presence of subsequent treatment after ASCT in a time-dependent model. Conclusion: Given the high survival outcomes, ASCT is a valuable treatment option for relapsed/refractory DLBCL. However, only a small subset of patients is fit enough to benefit from this treatment and patients who fail ASCT have a poor prognosis. Therefore, novel therapeutic approaches are required to address these unmet medical needs.

APOE Genotype and Alzheimer Disease Risk Across Age, Sex, and Population Ancestry

Apolipoprotein E (APOE)*2 and APOE*4 are, respectively, the strongest protective and risk-increasing, common genetic variants for late-onset Alzheimer disease (AD), making APOE status highly relevant toward clinical trial design and AD research broadly. The associations of APOE genotypes with AD are modulated by age, sex, race and ethnicity, and ancestry, but these associations remain unclear, particularly among racial and ethnic groups understudied in the AD and genetics research fields. To assess the stratified associations of APOE genotypes with AD risk across sex, age, race and ethnicity, and global population ancestry. This genetic association study included case-control, family-based, population-based, and longitudinal AD-related cohorts that recruited referred and volunteer participants. Data were analyzed between March 2022 and April 2023. Genetic data were available from high-density, single-nucleotide variant microarrays, exome microarrays, and whole-exome and whole-genome sequencing. Summary statistics were ascertained from published AD genetic studies. The main outcomes were risk for AD (odds ratios [ORs]) and risk of conversion to AD (hazard ratios [HRs]), with 95% CIs. Risk for AD was evaluated through case-control logistic regression analyses. Risk of conversion to AD was evaluated through Cox proportional hazards regression survival analyses. Among 68 756 unique individuals, analyses included 21 852 East Asian (demographic data not available), 5738 Hispanic (68.2% female; mean [SD] age, 75.4 [8.8] years), 7145 non-Hispanic Black (hereafter referred to as Black) (70.8% female; mean [SD] age, 78.4 [8.2] years), and 34 021 non-Hispanic White (hereafter referred to as White) (59.3% female; mean [SD] age, 77.0 [9.1] years) individuals. There was a general, stepwise pattern of ORs for APOE*4 genotypes and AD risk across race and ethnicity groups. Odds ratios for APOE*34 and AD risk attenuated following East Asian (OR, 4.54; 95% CI, 3.99-5.17),White (OR, 3.46; 95% CI, 3.27-3.65), Black (OR, 2.18; 95% CI, 1.90-2.49) and Hispanic (OR, 1.90; 95% CI, 1.65-2.18) individuals. Similarly, ORs for APOE*22+23 and AD risk attenuated following White (OR, 0.53, 95% CI, 0.48-0.58), Black (OR, 0.69, 95% CI, 0.57-0.84), and Hispanic (OR, 0.89; 95% CI, 0.72-1.10) individuals, with no association for Hispanic individuals. Deviating from the global pattern of ORs, APOE*22+23 was not associated with AD risk in East Asian individuals (OR, 0.97; 95% CI, 0.77-1.23). Global population ancestry could not explain why Hispanic individuals showed APOE associations with less pronounced AD risk compared with Black and White individuals. Within Black individuals, decreased global African ancestry or increased global European ancestry showed a pattern of APOE*4 dosage associated with increasing AD risk, but no such pattern was apparent for APOE*2 dosage with AD risk. The sex-by-age-specific interaction effect of APOE*34 among White individuals (higher risk in women) was reproduced but shifted to ages 60 to 70 years (OR, 1.48; 95% CI, 1.10-2.01) and was additionally replicated in a meta-analysis of Black individuals and Hispanic individuals (OR, 1.72; 95% CI, 1.01-2.94). Through recent advances in AD-related genetic cohorts, this study provided the largest-to-date overview of the association of APOE with AD risk across age, sex, race and ethnicity, and population ancestry. These novel insights are critical to guide AD clinical trial design and research.

Toward Precision Medicine: Development and Validation of A Machine Learning Based Decision Support System for Optimal Sequencing in Castration-Resistant Prostate Cancer.

Selecting a patient-specific sequencing strategy to maximize survival outcomes is a clinically unmet need for patients with castration-resistant prostate cancer (CRPC). We developed and validated an artificial intelligence-based decision support system (DSS) to guide optimal sequencing strategy selection. Clinicopathological data of 46 covariates were retrospectively collected from 801 patients diagnosed with CRPC at 2 high-volume institutions between February 2004 and March 2021. Cox-proportional hazards regression survival (Cox) modeling in extreme gradient boosting (XGB) was used to perform survival analysis for cancer-specific mortality (CSM) and overall mortality (OM) according to the use of abiraterone acetate, cabazitaxel, docetaxel, and enzalutamide. The models were further stratified into first-, second-, and third-line models that each provided CSM and OM estimates for each line of treatment. The performances of the XGB models were compared with those of the Cox models and random survival forest (RSF) models in terms of Harrell's C-index. The XGB models showed greater predictive performance for CSM and OM compared to the RSF and Cox models. C-indices of 0.827, 0.807, and 0.748 were achieved for CSM in the first-, second-, and third-lines of treatment, respectively, while C-indices of 0.822, 0.813, and 0.729 were achieved for OM regarding each line of treatment, respectively. An online DSS was developed to provide visualization of individualized survival outcomes according to each line of sequencing strategy. Our DSS can be used in clinical practice by physicians and patients as a visualized tool to guide the sequencing strategy of CRPC agents.

Associations between upper quarter Y-balance test performance and sport-related injuries in adolescent handball players.

Handball players are at a high risk of suffering a sport-related injury. Recent studies in various adult populations (e.g., US Army soldiers/warrior athletes, and military members) showed that poor scores in the upper quarter Y-balance test (YBT-UQ) are related to an increased risk of injury. Yet, it is unclear whether this also applies to adolescent handball players. Thus, the present study aims to determine if pre-season YBT-UQ performance is associated with sport-related injuries during the competitive season in adolescent handball players. One hundred and thirty-three adolescent handball players (age: 15.4 ± 1.7years; m = 99, f = 42) who competed in the second highest league in the Rhine-Ruhr region, Germany, during the 2021/2022 season participated in the study. Before the competitive season, the players performed the YBT-UQ to assess upper extremity mobility and stability of the throwing and non-throwing arm. Over the 8-month competitive season, the coaches monitored the occurrence of sports-related injuries once a week, using an injury report form from the legal accident insurance. Fifty-seven players (43%) incurred a sport-related injury during the competitive season, of which 27 (47%) had upper body injuries, and 30 (53%) were lower body injuries. The YBT-UQ performance of the throwing and non-throwing arm did not significantly differ between injured and non-injured players. Further, Cox proportional hazard survival regression model analyses revealed that only the presence of an inferolateral reach asymmetry score ≥7.75% arm length was associated with a moderate increase in the risk (hazard ratio = 2.18, 95% confidence interval = 1.02-4.68, p = 0.045) of lower but not upper or whole-body injuries. Our findings suggest that the YBT-UQ has limited value as a field-based screening tool to assess the risk of sport-related injuries in adolescent handball players.

Tooth Retention and Clinical and Radiographic Long-Term Results Among Patients Treated with the Full-Mouth Laser-Assisted New Attachment Procedure (LANAP): A Case Series.

There are limited long-term treatment results for patients who receive full-mouth laser-assisted new attachment procedure (LANAP). The present study examined cases of full-mouth LANAP therapy for tooth retention, including clinical and radiographic changes. Sixty-six generalized stage III/IV periodontitis patients aged 30 to 76 years were identified via consecutive retrospective chart reviews in a private practice limited to periodontics. Following treatment with the LANAP protocol, differences between baseline and the patient's most recent periodontal maintenance visit (mean: 6.7 years) were determined regarding interproximal probing depths (iPD) and interproximal bone loss (iBL) percentages. Factors affecting tooth loss were analyzed using Cox proportional hazard regression survival analysis. The average tooth loss for the study population was 0.11 teeth/patient/year. Premolars were more likely to be retained compared to the reference group of incisors (hazard ratio = 0.38; 95% CI = 0.16 to 0.90; P = .03), adjusting for canines, molars, and other potential confounding factors. Age at the time of LANAP treatment, gender, history of diabetes, and baseline iBL and iPD were all significantly associated with tooth loss after full-mouth LANAP treatment. Clinical changes in iPD were more significant among premolars and molars when followed up for a period of less than 7 years. Tooth retention after full-mouth LANAP treatment was favorable in this cohort of private practice patients. Int J Periodontics Restorative Dent 2023;43:181-191. doi: 10.11607/prd.6418.

Does the Timing of Eribulin Treatment for Advanced or Metastatic Breast Cancer Matter? Evidence from a Real-World Setting

Background: This study aimed to examine the effectiveness and safety of eribulin used as an early-line (EL, i.e., first-/second-line) versus late-line (LL, i.e., third-line and beyond) chemotherapy for recurrent advanced or metastatic breast cancer (A/MBC) patients. Methods: This study conducted a retrospective observation of A/MBC patients initiating eribulin between January 1, 2015, and June 30, 2019, using medical database at a university-affiliated teaching hospital in Taiwan. Patients were assigned into either the EL or LL group based on the timing of respective eribulin treatments and were observed for at least 6 months up to December 2019 for progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), disease response, and occurrence of adverse events. The Kaplan-Meier and Cox proportional hazard regression survival analyses were performed. Results: Of 127 patients, 23.6% (n = 30) and 76.4% (n = 97) were assigned to the EL and LL groups, respectively, between which no difference in patient characteristics was noted. Median PFS and TTF were 6.5 months and 5.0 months for the EL and 4.2 months and 3.4 months for the LL, respectively. Median OS could not be estimated in the EL group and was 20.5 months in the LL group. Eribulin as an EL treatment was the only factor associated with longer TTF and OS, whereas the number of metastatic sites was additionally associated with PFS in the multivariate analysis. No complete response was reported in either group, but a partial response was obtained in 6.7% in the EL group and 3.1% in the LL group. The common adverse events between two groups were similar, including leukopenia (80.0%), neutropenia (76.7%), and anemia (60.0%). Conclusions: The eribulin used as an EL of chemotherapy was effective for A/MBC patients with known toxicities in this study, while eribulin as the LL chemotherapy showed consistent results with previous reports.

Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society

BackgroundThere is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody–drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer.MethodsUsing nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan–Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups.ResultsHER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49–0.93; P = 0.019).ConclusionsThese findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.

Effect of Statin Intensity on the Progression of Cardiac Allograft Vasculopathy.

Background: In the non-transplant population, hyperlipidaemia has shifted from targeting LDL goals to statin intensity-based treatment. It is unknown whether this strategy is also beneficial in cardiac transplantation. Methods: This single-centre retrospective study evaluated the effect of statin use and intensity on time to cardiac allograft vasculopathy (CAV) after cardiac transplantation. Kaplan–Meier and Cox proportional hazards regression survival methods were used to assess the association of statin intensity and median post-transplant LDL on CAV-free survival. Results: The study involved 143 adults (71% men, average follow-up of 25 ± 14 months) who underwent transplant between 2013 and 2017. Mean CAV-free survival was 47.5 months (95% CI [43.1–51.8]), with 29 patients having CAV grade 1 or greater. Median LDL was not associated with time to CAV (p=0.790). CAV-free survival did not differ between intensity groups (p=0.435). Conclusion: Given the non-statistically significant difference in time to CAV with higher intensity statins, the data suggest that advancing moderate- or high-intensity statin after cardiac transplantation may not provide additional long-term clinical benefit. Trial registration: Not applicable.

Survival outcomes and prognostic factors of papillary serous adenocarcinoma and papillary squamous cell carcinoma of the uterine cervix

The aim of this retrospective population-based study was to investigate the survival outcomes and prognostic factors of patients with the two cervical carcinomas. A cohort of patients diagnosed with papillary serous adenocarcinoma of the uterine cervix (PSAC) and papillary squamous cell carcinoma (PSCC) between 1973 and 2015 were drawn from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method, and prognostic factors were assessed using Cox proportional hazards survival regression analysis. The 5-year and 10-year OS rates were 38.4 and 33.1% for PSAC and 64.6 and 50.8% for PSCC, respectively. The 2-year and 5-year CSS rates were 60.6 and 45.9% for PSAC and 79.6 and 69.0% for PSCC, respectively. Patients with PSCC survive longer than PSAC patients and have other well-described prognostic factors for improved survival rates, including an early cancer stage, a younger patient age and standardised surgery. Impact statement What is already known on this subject? Papillary serous adenocarcinoma of the uterine cervix (PSAC) and papillary squamous cell carcinoma (PSCC)are both very rare subtypes of cervical carcinomas. What do the results of this study add? This retrospective population-based analysis has evaluated the survival outcomes and prognostic indicators of patients with PSAC and PSCC. What the implications are of these findings for clinical practice and/or further research? Knowing the survival outcomes and prognostic indicators of PSAC and PSCC patients, we can better follow up patients.

Feasibility and Outcomes of a Standardized Management Protocol for Acute Exacerbation of Interstitial Lung Disease.

Despite the high mortality of acute exacerbations of interstitial lung disease (AE-ILD), there is minimal evidence to guide management decisions. We aimed to assess the feasibility and outcomes of a standardized management protocol for AE-ILD. We performed a retrospective cohort study of patients with AE-ILD admitted to hospital between January 2015 and August 2019. Patients were managed with a standardized protocol including chest computed tomography (CT) at diagnosis, pulse corticosteroid treatment, and a follow-up CT 7 days after corticosteroid pulse. The association between idiopathic pulmonary fibrosis (IPF) versus non-IPF diagnosis and transplant-free survival within 1-year of AE-ILD was assessed using adjusted Cox proportional hazards regression survival analysis. Associations with CT chest improvement 7 days after corticosteroid pulse were secondarily assessed. 89 patients with AE-ILD were identified. 1-year transplant-free and overall survival were 20.2 and 51.7%, respectively. Protocol adherence to pulse corticosteroids was high (95.5%). A diagnosis of IPF was associated with higher risk of death or transplant at 1-year versus a non-IPF diagnosis [hazard ratio (HR) 2.23, 95% CI 1.19-4.17, p = 0.012]. There were no significant associations with 7-day CT improvement; however, CT improvement was associated with higher transplant-free survival (p = 0.02) and a lower risk of in-hospital mortality (χ2 = 7.06, p = 0.01) on unadjusted analysis. IPF is associated with a higher risk of death or transplant at 1-year as compared to a non-IPF diagnosis in patients with AE-ILD managed using a standardized protocol. Improvement on CT chest 7 days after corticosteroid pulse is associated with better survival.

A systematic review of the quality of conduct and reporting of survival analyses of tuberculosis outcomes in Africa

BackgroundSurvival analyses methods (SAMs) are central to analysing time-to-event outcomes. Appropriate application and reporting of such methods are important to ensure correct interpretation of the data. In this study, we systematically review the application and reporting of SAMs in studies of tuberculosis (TB) patients in Africa. It is the first review to assess the application and reporting of SAMs in this context.MethodsSystematic review of studies involving TB patients from Africa published between January 2010 and April 2020 in English language. Studies were eligible if they reported use of SAMs. Application and reporting of SAMs were evaluated based on seven author-defined criteria.ResultsSeventy-six studies were included with patient numbers ranging from 56 to 182,890. Forty-three (57%) studies involved a statistician/epidemiologist. The number of published papers per year applying SAMs increased from two in 2010 to 18 in 2019 (P = 0.004). Sample size estimation was not reported by 67 (88%) studies. A total of 22 (29%) studies did not report summary follow-up time. The survival function was commonly presented using Kaplan-Meier survival curves (n = 51, (67%) studies) and group comparisons were performed using log-rank tests (n = 44, (58%) studies). Sixty seven (91%), 3 (4.1%) and 4 (5.4%) studies reported Cox proportional hazard, competing risk and parametric survival regression models, respectively. A total of 37 (49%) studies had hierarchical clustering, of which 28 (76%) did not adjust for the clustering in the analysis. Reporting was adequate among 4.0, 1.3 and 6.6% studies for sample size estimation, plotting of survival curves and test of survival regression underlying assumptions, respectively. Forty-five (59%), 52 (68%) and 73 (96%) studies adequately reported comparison of survival curves, follow-up time and measures of effect, respectively.ConclusionThe quality of reporting survival analyses remains inadequate despite its increasing application. Because similar reporting deficiencies may be common in other diseases in low- and middle-income countries, reporting guidelines, additional training, and more capacity building are needed along with more vigilance by reviewers and journal editors.

Patients with Severe Right Ventricular Dysfunction and Low Arterial Elastance Have Poor Prognosis Even after Heart Transplantation

<h3>Purpose</h3> To study the impact of severe right ventricular (RV) dysfunction on survival after heart transplantation <h3>Methods</h3> Data from 250 patients was analyzed for the effect of severe RV dysfunction , categorized by high right atrial pressure (RAP), low pulmonary artery pulsatility index (PAPi) and the presence of ascites, on 90 day and medium term survival . Systemic afterload was estimated by arterial elastance (<i>E_a</i>) (method given below) and systemic vascular resistance (SVR) . <i>Calculation of E_a: End systolic pressure E_sys) = (2* systolic blood pressure + diastolic pressure) / 3 . (1) Stroke volume (SV) = (CO / HR). (2) Arterial Elastance (E_a ) = E_sys / SV (3)</i> Organ perfusion pressure index (OPPI) ((Mean arterial pressure - RAP) / BSA) and modified MELD score was calculated . <h3>Results</h3> 90 day survival was worse with RAP > 15 (p = 0.014 ) , PAPi < 0.9 (p= 0.104) ,with ascites (p = 0.005) <i>,</i> higher MELD score ( odds ratio 1.07, p = 0.06 ) and lower OPPI (odds ratio 0.92,p = 0.004). The effect of RAP ,PAPi and MELD score on mortality was not seen if afterload was higher (<i>Ea > 2.7,SVR >1600 dynes/cm^-5/sec).</i> 5 years survival was worse for RAP > 15 ( p = 0.0059) , ascites (p = 0.009), PAPi < 0.9 (p= 0.1897) and MELD score > 20 ( p=0.022 ) This effect of RAP , PAPi and MELD score was absent if Ea > 2.7. Survival for OPPI < 40 was worse (p = 0.0124) but only if RAP was more than 15 mm hg. The relationship between RAP,Ea and OPPI and the effect on medium term survival is shown in a cox proportional hazard regression survival curve ( Fig 1). <h3>Conclusion</h3> 90 day and 5 year survival after heart transplantation are worse in patients with severe preoperative RV dysfunction but only <i>if the systemic arterial afterload</i> is low . Organ perfusion pressure index less than 40 appears to be deleterious in the short and medium term. Vasodilator drugs used to treat systolic left heart failure may adversely affect survival if RAP is high . Intra aortic balloon pump might be a more physiological alternative in patients awaiting transplantation.

Incidence, Survival and Prognostic Factors of Oesophagogastric Cancer

Oesophagogastric cancer is one of the leading causes of cancer death worldwide due to its aggressive nature. Despite the high mortality rate, there is limited information regarding this cancer in Brunei. To estimate the incidence and survival duration of oesophagogastric cancer patients, to identify prognostic factors of oesophagogastric cancer and associated factors for late-stage oesophagogastric cancer detection. A retrospective study on all oesophagogastric cancer patients registered in the population-based national cancer registry in Brunei from January 2010 to December 2018. Kaplan-Meier and Cox proportional hazard regression survival analyses and multiple logistic regression were applied. Sixty-eight oesophagogastric cancer patients' data were retrieved from the registry. The incidence was 2.75 cases per 100,000 adults per year. Median survival time was 1.18 years (95% CI: 0.77, 1.80) and the 3-year survival rate was 26.3%. Age (61-70 years) (adjusted HR = 0.38; 95% CI: 0.17, 0.89; p = 0.025) and those who have undergone chemotherapy (adj. HR = 0.40; 95% CI: 0.18, 0.90; p = 0.026) have a significantly lower mortality risk. Obesity (adj. HR = 11.94; 95% CI: 1.94, 73.36; p = 0.007), and stage 4 (advanced stage) cancer (adj. HR=4.11; 95% CI: 1.97, 8.58; p< 0.001) have a significantly higher mortality risk. Females have 3-time odds (adj. OR = 3.05; 95% CI: 1.09, 9.02; p = 0.038) of presenting with stage 4 cancer. Smokers have 13-time odds (Adj. OR=12.99; 95% CI: 1.92, 262.0; p = 0.025) of presenting with stage 4 cancer. Prognosis of oesophagogastric cancer remains poor. Addressing late detection and improve endoscopic surveillance and awareness of symptoms may help improve prognosis and mortality.