Trends in the survival of patients with trisomy 13 from 1995 to 2021: A population study in Japan.

It remains unclear whether recent changes in the prognosis and management of patients with trisomy 13 impact patient survival. We investigated changes in survival of patients with trisomy 13 in Japan. Data from the Vital Statistics Database in Japan was retrieved to examine the association of sex, surgical history, and years of birth and death with changes in survival patterns in 1164 patients with trisomy 13 between 1995 and 2021. The rates of deaths due to trisomy 13 increased from 9.8% to 23.1% in those over 1 year of age and from 7.3% to 19.2% in those within 24 h of birth between 1995 and 2021. The median survival time was longer in 2009-2021 than in 1996-2008 (40 vs. 84 days, p < 0.001). The median survival time and the rate of patients with surgical history increased from 91 days and 16.0% in 1996-2008 to 179 days and 28.0% in 2009-2021, respectively. Median survival time among patients with trisomy 13 has increased over the last 26 years, with almost 1 in 3 patients currently surviving for more than 1 year. The increased surgical intervention rate might have contributed to this improvement.

Fertility-sparing surgery vs standard surgery for early-stage cervical cancer: difference in 5-year life expectancy by tumor size.

BACKGROUND: Cervical cancer incidence among premenopausal women is rising, and fertility-sparing surgery serves as an important option for this young population. There is a lack of evidence on what tumor size cutoff should be used to define candidacy for fertility-sparing surgery. OBJECTIVE: We sought to describe how the association between fertility-sparing surgery (compared with standard surgery) and life expectancy varies by tumor size among patients with cervical cancers measuring ≤4 cm in largest diameter. Our secondary objective was to quantify the probability of undergoing adjuvant radiotherapy among patients who underwent fertility-sparing surgery as a function of tumor size. STUDY DESIGN: We identified patients in the National Cancer Database aged ≤45 years, diagnosed with stage I cervical cancer with tumors ≤4 cm between 2006 and 2018, who received no preoperative radiation or chemotherapy, and who underwent either fertility-sparing surgery (cone or trachelectomy, either simple or radical) or standard surgery (simple or radical hysterectomy) as their primary treatment. Propensity-score matching was performed to compare patients who underwent fertility-sparing surgery with those who underwent standard surgery. A flexible parametric model was employed to quantify the difference in life expectancy within 5 years of diagnosis (restricted mean survival time) based on tumor size among patients who underwent fertility-sparing and those who underwent standard surgery. In addition, among those who underwent fertility-sparing surgery, a logistic regression model was used to explore the relationship between tumor size and the probability of receiving adjuvant radiation. RESULTS: A total of 11,946 patients met the inclusion criteria of whom 904 (7.6%) underwent fertility-sparing surgery. After propensity-score matching, 897 patients who underwent fertility-sparing surgery were matched 1:1 with those who underwent standard surgery. Although the 5-year life expectancy was similar among patients who had fertility sparing surgery and those who had standard surgery regardless of tumor sizes, the estimates of life-expectancy differences associated with fertility-sparing surgery were more precise among patients with smaller tumors (1-cm tumor: restricted mean survival time difference, -0.10 months; 95% confidence interval, -0.67 to 0.47) than among those with larger tumors (4-cm tumor: restricted mean survival time difference, -0.11 months; 95% confidence interval, -3.79 to 3.57). The probability of receiving adjuvant radiation increased with tumor size, ranging from 5.6% (95% confidence interval, 3.9-7.9) for a 1-cm tumor to 37% (95% confidence interval, 24.3-51.8) for a 4-cm tumor. CONCLUSION: Within 5 years of diagnosis, young patients with stage I cancers measuring ≤4 cm had similar survival outcomes after either fertility-sparing surgery or standard surgery. However, because few patients with tumors >2 cm underwent fertility-sparing surgery, a clinically important survival difference could not be excluded in this population.

Is Prophylactic Radiotherapy to the Lymphatic Drainage Area Necessary for Patients With Stage III Ovarian Cancer After Chemotherapy Following Surgery?

BACKGROUND: For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT). Here we assessed the therapeutic efficacy and toxicity of postoperative radiotherapy to the abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients, who had all received surgery and chemotherapy (CT). METHODS: We retrospectively collected patients with stage III epithelial ovarian cancer after cytoreductive surgery (CRS) and full-course adjuvant CT. The chemoradiotherapy (CRT) group patients were treated with intensity modulated radiotherapy (IMRT) to the abdominal and pelvic lymphatic drainage area in our hospital between 2010 and 2020. A propensity score matching analysis was conducted to compare the results between the CRT and CT groups. Kaplan-Meier analysis estimated overall survival (OS), disease-free survival (DFS), and local control (LC) rates. The log-rank test determined the significance of prognostic factors. RESULTS: A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CRT and RT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumour, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median DFS time, 5-year OS, and local recurrence free survival (LRFS) were 100.0 months vs 25.9 months (P = .020), 69.2% vs 49.9% (P = .002), and 85.9% vs 50.5% (P = .020), respectively. The CRT group mainly presented with acute haematological toxicities, with no statistically significant difference compared with grade III intestinal adverse effects (3/44 vs 6/88, P = .480). CONCLUSION: This report demonstrates that long-term DFS could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to the abdominal and pelvic lymphatic area. Compared with the CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.

RMST-based multiple contrast tests in general factorial designs.

Several methods in survival analysis are based on the proportional hazards assumption. However, this assumption is very restrictive and often not justifiable in practice. Therefore, effect estimands that do not rely on the proportional hazards assumption are highly desirable in practical applications. One popular example for this is the restricted mean survival time (RMST). It is defined as the area under the survival curve up to a prespecified time point and, thus, summarizes the survival curve into a meaningful estimand. For two-sample comparisons based on the RMST, previous research found the inflation of the type I error of the asymptotic test for small samples and, therefore, a two-sample permutation test has already been developed. The first goal of the present paper is to further extend the permutation test for general factorial designs and general contrast hypotheses by considering a Wald-type test statistic and its asymptotic behavior. Additionally, a groupwise bootstrap approach is considered. Moreover, when a global test detects a significant difference by comparing the RMSTs of more than two groups, it is of interest which specific RMST differences cause the result. However, global tests do not provide this information. Therefore, multiple tests for the RMST are developed in a second step to infer several null hypotheses simultaneously. Hereby, the asymptotically exact dependence structure between the local test statistics is incorporated to gain more power. Finally, the small sample performance of the proposed global and multiple testing procedures is analyzed in simulations and illustrated in a real data example.

Comparison between asymptotic and re-randomisation tests under non-proportional hazards in a randomised controlled trial using the minimisation method.

BACKGROUND: Pocock-Simon's minimisation method has been widely used to balance treatment assignments across prognostic factors in randomised controlled trials (RCTs). Previous studies focusing on the survival outcomes have demonstrated that the conservativeness of asymptotic tests without adjusting for stratification factors, as well as the inflated type I error rate of adjusted asymptotic tests conducted in a small sample of patients, can be relaxed using re-randomisation tests. Although several RCTs using minimisation have suggested the presence of non-proportional hazards (non-PH) effects, the application of re-randomisation tests has been limited to the log-rank test and Cox PH models, which may result in diminished statistical power when confronted with non-PH scenarios. To address this issue, we proposed two re-randomisation tests based on a maximum combination of weighted log-rank tests (MaxCombo test) and the difference in restricted mean survival time (dRMST) up to a fixed time point τ , both of which can be extended to adjust for randomisation stratification factors. METHODS: We compared the performance of asymptotic and re-randomisation tests using the MaxCombo test, dRMST, log-rank test, and Cox PH models, assuming various non-PH situations for RCTs using minimisation, with total sample sizes of 50, 100, and 500 at a 1:1 allocation ratio. We mainly considered null, and alternative scenarios featuring delayed, crossing, and diminishing treatment effects. RESULTS: Across all examined null scenarios, re-randomisation tests maintained the type I error rates at the nominal level. Conversely, unadjusted asymptotic tests indicated excessive conservatism, while adjusted asymptotic tests in both the Cox PH models and dRMST indicated inflated type I error rates for total sample sizes of 50. The stratified MaxCombo-based re-randomisation test consistently exhibited robust power across all examined scenarios. CONCLUSIONS: The re-randomisation test is a useful alternative in non-PH situations for RCTs with minimisation using the stratified MaxCombo test, suggesting its robust power in various scenarios.

Risk factors for bacteremic pneumonia and mortality (28-day mortality) in patients with Acinetobacter baumannii bacteremia.

BACKGROUND: Patients infected with Acinetobacter baumannii (AB) bacteremia in hospital have high morbidity and mortality. We analyzed the clinical characteristics of pneumonia and nonpneumonia-related AB bloodstream infections (AB BSIs) and explored the possible independent risk factors for the incidence and prognosis of pneumonia-related AB BSIs. METHODS: A retrospective monocentric observational study was performed. All 117 episodes of hospital-acquired AB bacteremia sorted into groups of pneumonia-related AB BSIs (n = 45) and nonpneumonia-related AB BSIs (n = 72) were eligible. Univariate/multivariate logistic regression analysis was used to explore the independent risk factors. The primary outcome was the antibiotic susceptibility in vitro of pneumonia-related AB BSIs group. The secondary outcome was the independent risk factor for the pneumonia-related AB BSIs group. RESULTS: Among 117 patients with AB BSIs, the pneumonia-related group had a greater risk of multidrug resistant A. baumannii (MDRAB) infection (84.44%) and carbapenem-resistant A. baumannii (CRAB) infection (80%). Polymyxin, minocycline and amikacin had relatively high susceptibility rates (> 80%) in the nonpneumonia-related group. However, in the pneumonia-related group, only polymyxin had a drug susceptibility rate of over 80%. Univariate analysis showed that survival time (day), CRAB, MDRAB, length of hospital stay prior to culture, length of ICU stay prior to culture, immunocompromised status, antibiotics used prior to culture (n > = 3 types), endotracheal tube, fiberoptic bronchoscopy, PITT, SOFA and invasive interventions (n > = 3 types) were associated with pneumonia-related AB bacteremia. The multivariate logistic regression analysis revealed that recent surgery (within 1 mo) [P = 0.043; 0.306 (0.098-0.962)] and invasive interventions (n > = 3 types) [P = 0.021; 0.072 (0.008-0.671)] were independent risk factors related to pneumonia-related AB bacteremia. Multivariate logistic regression analysis revealed that length of ICU stay prior to culture [P = 0.009; 0.959 (0.930-0.990)] and recent surgery (within 1 mo) [P = 0.004; 0.260 (0.105-0.646)] were independent risk factors for mortality in patients with pneumonia-related AB bacteremia. The Kaplan‒Meier curve and the timing test showed that patients with pneumonia-related AB bacteremia had shorter survival time compared to those with nonpneumonia-related AB bacteremia. CONCLUSIONS: Our study found that A. baumannii had a high rate of antibiotic resistance in vitro in the pneumonia-related bacteremia group, and was only sensitive to polymyxin. Recent surgery was a significantly independent predictor in patients with pneumonia-related AB bacteremia.

Role of PAR1 -506 deletion/insertion polymorphism in primary sclerosing cholangitis.

AIM: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by inflammation of the intra- and extrahepatic bile ducts. Pathogenesis of PSC is still enigmatic but is likely to be multifactorial. Recently, we identified an interleukin-6 (IL-6)-dependent signal transducer and activator of transcription 3 (STAT3) activation in CD4+ TH1 and TH17 cells in PSC. The IL-6/STAT3 pathway was shown to be regulated by protease-activated receptor 1 (PAR1) contributing to inflammation. The role of the PAR1 -506 deletion/insertion (Del/Ins) polymorphism in PSC has not yet been investigated. METHODS: Two hundred eighty four PSC patients (200 patients with inflammatory bowel diseases [IBD] and 84 without IBD) and 309 healthy controls were genotyped for PAR1 rs11267092 (-506 Del/Ins -13 bp). Results were correlated with clinical characteristics and transplant-free survival. RESULTS: The frequency of PAR1 -506 Ins allele carriers (Del/Ins and Ins/Ins) was significantly higher in PSC patients (57.0%) compared to healthy controls (39.8%). Furthermore, carriers of PAR1 -506 Ins allele were more likely to have PSC than noncarriers (odds ratio 2.01; 95% confidence interval, 1.45-2.79). Patients with PSC carrying the PAR1 -506 Ins allele showed significantly higher alanine aminotransferase serum levels (p = 0.0357) and a trend toward shorter transplant-free survival time compared to noncarriers (8.9 ± 6.6 years vs. 10.5 ± 7.1 years; p = 0.076). CONCLUSIONS: Our study shows that PAR1 -506 Ins is significantly more frequent in people with PSC. As PAR1 -506 Ins allele carriers tended to have a shorter transplant-free survival, PAR1 might play a role in the development and course of PSC.

Exploring the effects of acceptable palliative care models on survival time and healthcare expenditure among patients with cancer: a national longitudinal population-based study.

OBJECTIVE: Hospice care ensures better end-of-life quality by relieving terminal symptoms. Prior research has indicated that hospice care could prolong survival and reduce end-of-life medical expenditures among patients with cancer. However, the dearth of studies on the effects of hospice care type and use sequence on survival time and end-of-life medical expenditures substantiates the need for investigation. DATA SOURCES AND STUDY SETTING: Two million random records were obtained from the National Health Insurance Research Database. STUDY DESIGN: We estimated the effects of the type and sequence of hospice care use on survival time and medical expenditures among advanced cancer patients. This was a cross-sectional study. DATA COLLECTION/EXTRACTION METHODS: Patient data were collected from 2 million random records provided by the National Health Insurance Research Database of Taiwan. We included people with cancer and excluded patients under 20 years of age; 2860 patients remained after matching. PRINCIPAL FINDINGS: The results indicated that the average survival time of patients who received inpatient palliative care (1022 days) was significantly shorter than that of patients who did not receive palliative care (P < 0.001), but the health care expenditure during the entire course of cancer therapy was not the lowest. Interestingly, patients who received inpatient palliative care had the lowest health care expenditure at 1 year or month before the end of life (P < 0.001). CONCLUSION: The type and sequence of palliative care affected the survival time and health care expenditures of cancer patients. Receiving palliative care did not prolong survival but rather reduced health care expenditures. The sequence of receiving palliative care significantly affected health care expenditures.

Assessing the survival time of women with breast cancer in Northwestern Ethiopia: using the Bayesian approach.

BACKGROUND: Despite the significant weight of difficulty, Ethiopia's survival rate and mortality predictors have not yet been identified. Finding out what influences outpatient breast cancer patients' survival time was the major goal of this study. METHODS: A retrospective study was conducted on outpatients with breast cancer. In order to accomplish the goal, 382 outpatients with breast cancer were included in the study using information obtained from the medical records of patients registered at the University of Gondar referral hospital in Gondar, Ethiopia, between May 15, 2016, and May 15, 2020. In order to compare survival functions, Kaplan-Meier plots and the log-rank test were used. The Cox-PH model and Bayesian parametric survival models were then used to examine the survival time of breast cancer outpatients. The use of integrated layered Laplace approximation techniques has been made. RESULTS: The study included 382 outpatients with breast cancer in total, and 148 (38.7%) patients died. 42 months was the estimated median patient survival time. The Bayesian Weibull accelerated failure time model was determined to be suitable using model selection criteria. Stage, grade 2, 3, and 4, co-morbid, histological type, FIGO stage, chemotherapy, metastatic number 1, 2, and >=3, and tumour size all have a sizable impact on the survival time of outpatients with breast cancer, according to the results of this model. The breast cancer outpatient survival time was correctly predicted by the Bayesian Weibull accelerated failure time model. CONCLUSIONS: Compared to high- and middle-income countries, the overall survival rate was lower. Notable variables influencing the length of survival following a breast cancer diagnosis were weight loss, invasive medullar histology, comorbid disease, a large tumour size, an increase in metastases, an increase in the International Federation of Gynaecologists and Obstetricians stage, an increase in grade, lymphatic vascular space invasion, positive regional nodes, and late stages of cancer. The authors advise that it is preferable to increase the number of early screening programmes and treatment centres for breast cancer and to work with the public media to raise knowledge of the disease's prevention, screening, and treatment choices.

Effect of complete mesocolic excision (cme) on long-term survival after right colectomy for cancer: multivariate meta-analysis and restricted mean survival time estimation.

INTRODUCTION: Debate exists concerning the impact of complete mesocolic excision (CME) on long-term oncological outcomes. The aim of this review was to condense the updated literature and assess the effect of CME on long-term survival after right colectomy for cancer. METHODS: PubMed, MEDLINE, Scopus, and Web of Science were searched through July 2023. The included studies evaluated the effect of CME on survival. The primary outcome was long-term overall survival. Restricted mean survival time difference (RMSTD), hazard ratio (HR), and 95% confidence intervals (CI) were used as pooled effect size measures. GRADE methodology was used to summarize the certainty of evidence. RESULTS: Ten studies (3665 patients) were included. Overall, 1443 (39.4%) underwent CME. The RMSTD analysis shows that at 60-month follow-up, stage I-III CME patients lived 2.5 months (95% CI 1.1-4.1) more on average compared with noCME patients. Similarly, stage III patients that underwent CME lived longer compared to noCME patients at 55-month follow-up (6.1 months; 95% CI 3.4-8.5). The time-dependent HRs analysis for CME vs. noCME (stage I-III disease) shows a higher mortality hazard in patients with noCME at 6 months (HR 0.46, 95% CI 0.29-0.71), 12 months (HR 0.57, 95% CI 0.43-0.73), and 24 months (HR 0.73, 95% CI 0.57-0.92) up to 27 months. CONCLUSIONS: This study suggests that CME is associated with unclear OS benefit in stage I-III disease. Caution is recommended to avoid overestimation of the effect of CME in stage III disease since the marginal benefit of a more extended resection may have been influenced by tumor biology/molecular profile and multimodal adjuvant treatments.

Dissecting the restricted mean time in favor of treatment.

The restricted mean time in favor (RMT-IF) summarizes the treatment effect on a hierarchical composite endpoint with mortality at the top. Its crude decomposition into "stage-wise effects," i.e., the net average time gained by the treatment prior to each component event, does not reveal the patient state in which the extra time is spent. To obtain this information, we break each stage-wise effect into subcomponents according to the specific state to which the reference condition is improved. After re-expressing the subcomponents as functionals of the marginal survival functions of outcome events, we estimate them conveniently by plugging in the Kaplan -- Meier estimators. Their robust variance matrices allow us to construct joint tests on the decomposed units, which are particularly powerful against component-wise differential treatment effects. By reanalyzing a cancer trial and a cardiovascular trial, we acquire new insights into the quality and composition of the extra survival times, as well as the extra time with fewer hospitalizations, gained by the treatment in question. The proposed methods are implemented in the rmt package freely available on the Comprehensive R Archive Network (CRAN).

Patients' perception of the benefits of palliative systemic therapy for advanced cancer.

BACKGROUND: Patients with advanced cancer who misunderstand their prognosis and chance of cure tend to overestimate the likely benefits of palliative systemic therapy. AIM: To determine patient perceptions of palliative systemic therapy benefits in advanced cancer. METHODS: We surveyed 104 outpatients with advanced cancer receiving systemic anticancer therapy and their treating oncologists. Patients recorded their understanding of treatment impact on chance of cure and symptoms. Life expectancy was estimated by patients and oncologists. A visual analogue scale (0-10) was used to record how patients and oncologists valued quality of life (QOL) and length of life (LOL) (<4 QOL most important; 4-7 QOL and LOL equal; >7 LOL most important). Patient-oncologist discordance was defined as a ≥4-point difference. RESULTS: The main reasons patients selected for receiving treatment were to live longer (54%) and cure their cancer (36%). Most patients reported treatment was very/somewhat likely to prolong life (84%) and improve symptoms (76%), whereas 20% reported treatment was very/somewhat likely to cure their cancer. 42% of patients selected a timeframe for life expectancy (choice of four timeframes between <1 year and ≥5 years); of these, 62% selected a longer timeframe than their oncologist. When making treatment decisions, 71% of patients (52% of oncologists) valued QOL and LOL equally. Patient-oncologist discordance was 21%, mostly because of oncologists valuing QOL more than their patients (70%). CONCLUSION: At least 20% of patients receiving systemic therapy for advanced cancer reported an expectation of cure. Most patients and oncologists value QOL and LOL equally when making treatment decisions.

Survival analysis of older adults with dementia: predicting factors after unplanned hospitalization in Maharaj Nakorn Chiang Mai Hospital.

BACKGROUND: Hospitalization in individuals with dementia can be associated with negative and unintended outcomes. Research indicates that people with dementia experience more hospital admissions in comparison to individuals without dementia. This study aims to assess the survival time of individuals with dementia who experience unplanned hospitalization and examine the factors that are associated with mortality in this population. METHODS: This retrospective cohort study was conducted using data from older adults with dementia who survived unplanned hospitalizations at Maharaj Nakorn Chiang Mai Hospital between January 1, 2009, and December 31, 2016. The association between factors and mortality were analyzed using a multivariable Cox proportional hazards model. RESULTS: One hundred and eighty-one cases were included. The mean age of the study population was 80.07 (SD 7.49) years, and the majority were female (56.91%). The median survival time of the studied cohort was 3.06 years (95% CI 3.14-3.60). The multivariable analysis revealed that older age (aHR = 1.02, 95% CI 1.00-1.05), a diagnosis of mixed-type dementia (aHR = 3.45, 95% CI 1.17-10.14), higher Charlson comorbidity index score (aHR = 1.19, 95% CI 1.04-1.36), higher serum creatinine level (aHR = 1.35, 95% CI 1.10-1.66), insertion of endotracheal tube (aHR = 1.95, 95% CI 1.07-3.54), and readmission within 30 days (aHR = 1.88, 95% CI 1.18-2.98) were associated with an increased risk of mortality. CONCLUSIONS: We identified several notable predictors of mortality. Healthcare providers can use the findings of this study to identify patients who may be at higher risk of mortality and develop targeted interventions which may improve patient outcomes.

Clinical diagnosis and treatment of 37 cases of gallbladder neuroendocrine carcinoma.

OBJECTIVE: This study aims to investigate the clinical and pathological characteristics, treatment approaches, and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC). METHODS: Retrospective analysis was conducted on the clinical data of 37 patients with GB-NEC admitted to Shanxi Cancer Hospital from January 2010 to June 2023. The study included an examination of their general information, treatment regimens, and overall prognosis. RESULTS: Twelve cases, either due to distant metastasis or other reasons, did not undergo surgical treatment and received palliative chemotherapy (Group 1). Two cases underwent simple cholecystectomy (Group 2); four patients underwent palliative tumor resection surgery (Group 3), and nineteen patients underwent radical resection surgery (Group 4). Among the 37 GB-NEC patients, the average pre-surgery CA19-9 level was 113.29 ± 138.45 U/mL, and the median overall survival time was 19 months (range 7.89-30.11 months). Of these, 28 cases (75.7%) received systemic treatment, 25 cases (67.6%) underwent surgical intervention, and 16 cases (64.0%) received postoperative adjuvant treatment, including combined radiochemotherapy or chemotherapy alone. The median overall survival time was 4 months (0.61-7.40 months) for Group 1 (n = 12), 8 months for Group 2 (n = 2), 21 months (14.67-43.33 months) for Group 3 (n = 4), and 19 months (range 7.89-30.11 months) for Group 4 (n = 19). A significant difference in median overall survival time was observed between Group 1 and Group 4 (P = 0.004). CONCLUSION: Surgery remains the primary treatment for GB-NEC, with radical resection potentially offering greater benefits to patient survival compared to other therapeutic options. Postoperative adjuvant therapy has the potential to extend patient survival, although the overall prognosis remains challenging.

Diagnostic and Prognostic Value of Circulating DNA Fragments in Glioblastoma Multiforme Patients.

Novel blood-circulating molecules, as potential biomarkers for glioblastoma multiforme (GBM) diagnosis and monitoring, are attracting particular attention due to limitations of imaging modalities and invasive tissue biopsy procedures. This study aims to assess the diagnostic and prognostic values of circulating cell-free DNA (cfDNA) in relation to inflammatory status in GBM patients and to determine the concentration and average size of DNA fragments typical of tumour-derived DNA fractions. Preoperative plasma samples from 40 patients (GBM 65.0 ± 11.3 years) and 40 healthy controls (HC 70.4 ± 5.4 years) were compared. The cfDNA concentrations and lengths were measured using the electrophoresis platform, and inflammatory indices (NLR, PLR, LMR, and SII) were calculated from complete blood cell analysis. More fragmented cfDNA and 4-fold higher 50-700 bp cfDNA concentrations were detected in GBM patients than in healthy controls. The average cfDNA size in the GBM group was significantly longer (median 336 bp) than in the HC group (median 271 bp). Optimal threshold values were 1265 pg/µL for 50-700 bp cfDNA (AUC = 0.857) and 290 bp for average cfDNA size (AUC = 0.814). A Kaplan-Meier survival curves analysis also demonstrated a higher mortality risk in the GBM group with a cut-off >303 bp cfDNA. This study is the first to have revealed glioblastoma association with high levels of cfDNA > 1000 pg/µL of 50-700 bp in length, which can be aggravated by immunoinflammatory reactivity.

Post-treatment stability, survival time and periodontal health associated with vacuum-formed, bonded and rapid prototype retainers: A prospective clinical study.

BACKGROUND: New technologies have paved the way for newer fabrication techniques, such as rapid prototyping, which has gained popularity in the fabrication of several orthodontic appliances including retainers. AIM: To evaluate the stability, survival time and periodontal health associated with vacuum-formed retainers (VFRs), bonded retainers (BRs) and rapid prototype retainers (RPRs) over a period of 12 months in retention. STUDY DESIGN: Prospective clinical study. METHODS: A total of 72 participants completing fixed orthodontic treatment were allocated to the following three groups by the investigators based upon their initial malocclusion, compliant and preferences: VFR; BR; and RPR. The primary outcome was Little's Irregularity Index (LII). Other stability parameters, including arch length (AL), inter-canine width (ICW) and inter-molar width (IMW), were also assessed immediately after debonding (T0) and 12 months (T2) after debonding. In addition, survival time, and calculus index and gingival index (GI) were assessed. RESULTS: LII showed a significant difference (P = 0.00) between the groups and was increased in the VFR group (0.18 ± 0.22 mm) compared to the BR (0.03 ± 0.05 mm) and RPR (0.01 ± 0.03 mm) groups but was not clinically significant. The mean survival time of maxillary retainers was longest for the RPR group (220.63 days; 95% confidence interval [CI] = 194.1-247.16) but there was no significant difference between the three groups (P = 0.43). The mean survival time of mandibular retainers was higher and the same for the VFR and RPR groups (240 days; 95% CI = 240-240) and there was no significant difference between the three groups (P = 0.38). The calculus index score (P = 0.00) was statistically significant between the groups, with an increased score for the BR group (0.33 ± 0.27) compared to the VFR (0.07 ± 0.16) and RPR (0.13 ± 0.22) groups. Similarly, the GI score (P = 0.02) was statistically significant between the groups and was increased in the BR group (0.01 ± 0.19) compared to the VFR (-0.15 ± 0.18) and RPR (-0.06 ± 0.15) groups. The increase in calculus index and GI scores for the BR group were not clinically significant. CONCLUSION: There were no clinically significant differences between the three retainer groups in terms of stability, periodontal health and time to failure.

Dura mater and survival time determination in individuals who died after traumatic brain injury: a preliminary study.

BACKGROUND: Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality among young people and is a matter of concern for forensic pathologists. Many authors have tried to estimate a person's survival time (ST) after TBI using different approaches. OBJECTIVE: The present study aimed to present an innovative workflow to estimate the ST after TBI by observing the inflammatory reaction of the dura mater (DM). METHODS: The authors collected DM samples from 36 cadavers (20 with TBI and 16 with no history or signs of TBI). Each sample was labelled via immunohistochemistry with three different primary antibodies, CD15, CD68, and CD3, yielding 108 slides in total. The slides were digitalized and analysed using QuPath software. RESULTS: The DM is involved in the inflammatory response after TBI. CD15 immunoreactivity allowed us to distinguish between subjects who died immediately after TBI and those with an ST of minutes or hours. CD3 immunoreactivity can be used to differentiate subjects with an ST of days from those with other STs. Moreover, the DM samples showed an acceptable diagnostic yield even in samples with signs of putrefaction.

Skin injuries in forensic histopathology: a descriptive study.

Histopathology is commonly used in forensic medicine. Only few studies are available in the literature about the correlation between skin wounds histopathology and survival time or other medicolegal data. The aim of this study was to illustrate the usefulness of histopathological analysis of skin wounds in forensic daily practice and to evaluate its correlation with the clinical and police investigation data. In this single-center, retrospective, and descriptive study, we included 198 forensic pathology cases, from the files of the Legal Medicine and Biopathology Departments of the University Hospital of Nancy, with a total of 554 skin samples. Basing on the police investigations (n = 43), the median survival time between the main related trauma and death was 83 min. The histopathological analysis concluded to 2% of post-mortem lesions (absence of hemorrhage) and 55% of perimortem or undetermined lesions (hemorrhage without inflammation); 8% of the lesions had an estimated time interval between more than 10 min and several hours, 22% between several hours and several days, and 14% between several days and several weeks. Histopathological dating was statistically associated with wound location (p < 0.01), the type of injury, hypothermia, positive toxicology, histopathological hepatic lesions, and survival time (p < 0.001). In conclusion, the histopathological analysis of skin wounds allowed to propose a survival time in almost half of cases, with a significant correlation with the police investigation-based estimation of survival time, but also other parameters such as wound location or toxicology. It however lacks of accuracy, and further studies are needed to develop new markers, notably based on immunohistochemistry.

Outcomes of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma: A tertiary center experience.

Objective: To assess the overall survival in patients with intermediate stage hepatocellular carcinoma following transarterial chemoembolization. Methods: It is a retrospective descriptive study carried out in the Department of Radiology of Liaquat National Hospital Karachi, Pakistan. Seventy-two patients were enrolled from July 2014 to December 2021 and had chemoembolization therapy. Patients were followed till their demise. Mean and Median survivals were calculated. Results: A total of 72 patients had a median survival of 15 months with 95% confidence interval (11 months was lower bound and 18 months was upper bound), 19 months was the mean survival time with 95% confidence interval (14.7 months was lower limit and 22.6 months the upper limit). The factors which had a significant impact on the median survival time were Child-Pugh classification, average size of tumor and embolization pattern. Conclusion: Transarterial chemoembolization (TACE) increases the median survival time effectively and safely in patients with hepatocellular carcinoma. However complete resolution of disease is not possible with TACE, with most patient eventually succumbing to the disease. The overall survival for TACE in this study correlates well with other studies. Child Pugh Class, tumor size and embolization pattern have significant effect on survival of patients.

Effectiveness of pembrolizumab in trial-ineligible patients with metastatic urothelial carcinoma.

BACKGROUND: The KEYNOTE-045 trial showed that pembrolizumab therapy improved the survival of patients with advanced urothelial carcinoma (UC). However, its effectiveness in trial-ineligible patients remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective study to evaluate the effectiveness of pembrolizumab in patients with metastatic UC who were trial-ineligible. The data of 164 consecutive patients with platinum-treated metastatic UC who received pembrolizumab as second-line therapy were analyzed. Trial eligibility was assessed using the KEYNOTE-045 criteria. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. Overall survival (OS) and progression-free survival (PFS) were examined using the IPTW-adjusted Kaplan-Meier method. IPTW-adjusted restricted mean survival times (RMSTs) were compared between ineligible and eligible patients. RESULTS: Seventy-five patients (45.7%) were classified as ineligible based on the KEYNOTE-045 criteria. Baseline hemoglobin concentration of less than 9.0 g/dL was the most common reason for trial protocol violation (N = 23 [14.0%]). An IPTW-adjusted logistic regression model showed that the trial-eligibility was not significantly associated with objective response (OR: 0.65, 95% CI: 0.32 to 1.29, P = 0.22). Ineligible patients had similar RMST for PFS (difference: 3.8 months, 95% CI: -1.6 to 9.3, P = 0.17) and RMST for OS (difference: 1.4 months, 95% CI: -5.4 to 8.2, P = 0.93) compared with eligible patients. CONCLUSIONS: This study suggests that the effectiveness of pembrolizumab may be retained in ineligible patients with platinum-treated metastatic UC. Expanding trial eligibility criteria for these patients may be beneficial.