Survival In Adults Research Articles

Physical Function and Survival in Older Adults: A longitudinal study accounting for time-varying effects

Purpose of the studyVariation in physical function in older adults over time raises several methodological challenges in the study of its association with survival, many of which have largely been overlooked in previous studies. The objective of this study is to examine the relationship between time-varying measures of physical function and survival in men and women aged 70 years and over, while accounting for the time-varying effects of health and lifestyle characteristics. Methods1,846 women and 1,245 men in the Cardiovascular Health Study followed annually for up to 10 years beginning at age 70-74 years were included. We estimated the effect of gait speed and grip strength on survival over the subsequent year, using age as the timescale. ResultsA 0.1m/s higher gait speed was associated with a 12% decrease in the likelihood of death in the subsequent year among women (HR 0.88, 95% CI 0.82-0.94). There was no statistically significant effect of gait speed on survival among men (HR 0.97, 95% CI 0.91 to 1.03), or of grip strength on survival among women (HR 0.97, 95% CI 0.95-1.00) or men (HR 0.99, 95% CI 0.97-1.01), over one year. ConclusionsUpon using time-varying measures of physical function while accounting for time-varying effects of health and lifestyle characteristics, higher gait speed was associated with increased survival among the women in our study. We found no evidence of an association between gait speed and one-year survival in men, or between grip strength and one-year survival in women or men.

Event free survival in adults with relapsed ALL who underwent front-line therapy with CALGB 10403.

e19005 Background: CALGB 10403 is a pediatric-inspired ALL regimen that has recently been shown to have improved survival rates in adolescents and young adults with ALL when compared to historical outcomes with traditional adult ALL regimens (Stock et. al, 2019). Methods: This is a retrospective cohort study of ALL patients who received induction CALGB 10403 at Stanford University (both on and off trial), achieved CR1, and subsequently relapsed. Primary outcome of interest was event free survival from time of diagnosis. Events were defined as relapse or death. Secondary outcomes were overall survival and event free survival from first relapse. Patients were censored at time of last clinical follow up. Results: 25 patients met inclusion criteria and received front-line CALGB 10403 from April 2010 to September 2018. At the time of initial diagnosis median age was 30 years (range 18 – 39 years). 68% of patients were male. 48% of patients were overweight and 40% were obese. 76% of patients had precursor B cell ALL while 24% had T cell ALL. 12% had CNS disease at diagnosis. 36% of patients had WBC greater than 30k. 12% of patients had CRLF2 rearrangement. 12% of patients were MRD positive after first induction. 20% of patients received rituximab. Median event free survival time from diagnosis was 20 months (range 3 – 79 months) and median overall survival time was 53 months. Blinatumomab was the most common salvage therapy after 1st relapse, followed by inotuzumab. 15 patients (60%) achieved CR2, of which 4 (27%) were MRD positive after 2nd induction. 15 patients (60%) went to HSCT. Of the patients who achieved CR2, 8 relapsed for a second time. Median event free survival time after first relapse was 23 months. Survival 1 year after relapse was 60%. 11 of the 25 patients were alive at last follow up. Median follow up time of survivors was 6 years. Conclusions: This is a descriptive retrospective cohort study of adult patients in a real world setting who received CALGB 10403 induction and subsequently relapsed. Compared to other studies of relapsed ALL patients who were induced with traditional chemotherapy (Fielding et. al, 2007), survival 1 year after relapse was much higher (60% vs. 22%). As CALGB 10403 becomes an increasingly common induction regimen for AYA and adults with ALL, further outcomes study is required.[Table: see text]

Association between baseline geriatric domains and survival in older adults with chronic lymphocytic leukemia (CLL).

12041 Background: CLL is a disease that commonly affects older adults. Although the value of geriatric assessment is increasingly being recognized in older adults with cancer, few studies have examined the relationship between baseline geriatric domains and clinical outcomes in older adults with CLL. Methods: We conducted a secondary data analysis of 369 adults diagnosed with CLL and treated in a phase 3 randomized trial of patients age ≥65 with bendamustine plus rituximab versus ibrutinib plus rituximab versus ibrutinib alone. We evaluated geriatric domains of functional status (activities of daily living [ADL], instrumental activities of daily living [IADL], Timed “Up and Go,” and number of falls in last 6 months), psychological status (Mental Health Inventory), social activity (Medical Outcomes Study [MOS] Social Activity Survey), cognition (Blessed Orientation Memory Concentration Test), social support (MOS Social Support Tangible and Emotional/Informational subscales), and nutritional status ( > 5% weight loss in the preceding 6 months). We examined associations among baseline geriatric domains with overall survival (OS) and progression-free survival (PFS) using multivariable Cox regression models. Results: The median age of patients was 71 years (range: 65-89). Most were male (67.1%) and had an ECOG performance status of 0 or 1 (96.9%). In multivariable models, the following geriatric domains were significantly associated with OS: better functional status (ADL score: HR 0.67, p = 0.012; IADL score: HR 0.98, p = 0.007); social activity score (HR 0.97, p = 0.004); and nutritional status (HR 2.58, p = 0.008). Similarly, functional status (ADL score: HR 0.77, p = 0.028; IADL score: HR 0.99, p = 0.007); social activity score (HR 0.97, p < 0.001); and nutritional status (HR 2.87, p < 0.001) were all associated with PFS. Additionally, the number of impaired geriatric domains was also associated with OS (HR 1.50, p = 0.004) and PFS (HR 1.45, p < 0.001). Timed “Up and Go”, number of falls in last 6 months, psychological status, cognition, and social support were not significantly associated with clinical outcomes. Conclusions: Geriatric domains of functional status, social activity, and nutritional status were associated with OS and PFS in this cohort of older adults with CLL. These findings highlight the importance of assessing geriatric domains to identify high-risk patients with CLL who may benefit from additional support during their treatment.

Toxicity, response, and survival in older adults with metastatic melanoma treated with checkpoint inhibitors.

9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastatic melanoma. Trials suggest no differences in outcomes between older and younger patients, but only relatively young patients with a good performance status were included in these trials. The aim of this study was to describe treatment patterns and outcomes of older adults with metastatic melanoma, and to identify predictors of outcome. Methods: We included all patients aged ≥65 years with metastatic melanoma between 2013 and 2020 from the Dutch Melanoma Treatment registry (DMTR), in which detailed information on patients, treatments and outcomes is available. We assessed predictors of grade ≥3 toxicity and 6-months response using logistic regression models, and melanoma-specific and overall survival using Cox regression models. Additionally, we described reasons for hospital admissions and treatment discontinuation. Results: A total of 2216 patients were included. Grade ≥3 toxicity did not increase with age, comorbidity or WHO performance status, in patients treated with monotherapy (anti-PD1 or ipilimumab) or combination treatment. However, patients aged ≥75 were admitted more frequently and discontinued treatment due to toxicity more often. Six months-response rates were similar to previous randomized trials (40.3% and 43.6% in patients aged 65-75 and ≥75 respectively for anti-PD1 treatment) and were not affected by age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity, but age, comorbidity and WHO performance status were associated with overall survival in multivariate analyses. Conclusions: Toxicity, response and melanoma-specific survival were not associated with age or comorbidity status. Treatment with immunotherapy should therefore not be omitted solely based on age or comorbidity. However, the impact of grade I-II toxicity in older patients deserves further study as older patients discontinue treatment more frequently and receive less treatment cycles.[Table: see text]

Overall survival after perioperative chemotherapy in the management of pulmonary metastasis in osteosarcoma.

e23508 Background: Pulmonary metastasectomy is performed on a select cohort of patients with advanced osteosarcoma with the potential for long term survival. However, evidence on peri-operative chemotherapy at time of metastasectomy is not completely understood and difficult to summarize without a systematic examination of existing literature. The purpose of this project is to perform a meta-analysis of existing studies to determine overall survival (OS) and prognostic factors in adults and children with advanced and recurrent osteosarcoma receiving chemotherapy around time of metastasectomy. Methods: We reviewed survival studies conducted in children and adults with advanced and recurrent osteosarcoma who undergo pulmonary metastasectomy published in English with more than 5 patients. The primary outcome was overall survival. Literature searches were performed in multiple electronic databases including Ovid MEDLINE (1946 to present), Ovid EMBASE (1974 to present), Web of Science, and Cochrane Library. Two investigators independently screened all citations, abstracts, and full-text articles. Results: 24 out of 80 observational studies between 1977 to 2018 were included. 2146 patients were studied of which 987 underwent pulmonary metastasectomy for osteosarcoma. 822 patients received perioperative chemotherapy in this setting. No randomized controlled trials were identified. Studies included patients from Asia, Africa, Europe, and North America. The median OS ranged between 20 to 90 months. 5-year OS ranged between 15 to 63%. Factors associated with survival included: age, number of lesions, disease free interval, time of development of metastases, number of lesions and laterality of pulmonary disease. Conclusions: Overall survival in study has a significant range. Factors influencing survival included intrinsic factors such as patient age and disease characteristics, as well as extrinsic factors such as evolution of chemotherapy regimen over the past four decades. The main limitations are related to the inherently low-quality evidence as a result of lack of randomized controlled trials. More comprehensive data is needed to guide shared decision making in this area.

Mismatch Repair Status Correlates with Survival in Young Adults with Metastatic Colorectal Cancer

BackgroundYoung adults with metastatic colorectal cancer (mCRC) may have higher rates of deficient mismatch repair (dMMR) than older patients. This study sought to assess patterns of MMR-testing and survival among young adult mCRC patients in the National Cancer Database (NCDB), hypothesizing that dMMR correlates with worse survival than in MMR-proficient (pMMR) patients. MethodsStage-IV colorectal cancers were identified in NCDB (2010-2016). Demographic and clinical features were compared between younger (age ≤ 30) and older mCRC patients and tested for association with overall survival. Stage-IV disease without other recorded metastatic sites defined peritoneal metastasis (PM). Fisher-exact tests compared proportions and Cox models tested association with overall survival. ResultsOf 124,587 stage-IV colorectal cancers, 1,123 (0.9%) were in young patients. Young patients were more likely to have mucinous histology, high-grade, rectal primaries, and isolated peritoneal metastases (P < 0.001). Younger patients more often had MMR-testing (29.1 versus 16.6%), with dMMR found at similar rates in young and older patients (21.7 versus 17.1% of those tested, P= 0.4). Despite higher rates of adverse prognostic features, younger patients had better survival (median 20.7 versus 14.8 months, P < 0.001). In MMR-tested patients, dMMR correlated with higher mortality risk compared to pMMR (median 16.6 months versus 25.5 months, P = 0.01). On multivariable analysis, grade and MMR-status remained independently associated with survival. ConclusionsMedian survival was worse with dMMR by 8.9 months compared to pMMR in young adults with mCRC. Despite higher rates of familial syndromes in young patients and recommendations for universal MMR-testing, over 70% of young mCRC patients had no MMR-status recorded.

In-Hospital 30-Day Survival Among Young Adults With Coronavirus Disease 2019: A Cohort Study.

BackgroundOur objective was to characterize young adult patients hospitalized with coronavirus disease 2019 (COVID-19) and identify predictors of survival at 30 days.MethodsThis retrospective cohort study took place at 12 acute care hospitals in the New York City area. Patients aged 18–39 hospitalized with confirmed COVID-19 between March 1 and April 27, 2020 were included in the study. Demographic, clinical, and outcome data were extracted from electronic health record reports.ResultsA total of 1013 patients were included in the study (median age, 33 years; interquartile range [IQR], 28–36; 52% female). At the study end point, 940 (92.8%) patients were discharged alive, 18 (1.8%) remained hospitalized, 5 (0.5%) were transferred to another acute care facility, and 50 (4.9%) died. The most common comorbidities in hospitalized young adult patients were obesity (51.2%), diabetes mellitus (14.8%), and hypertension (13%). Multivariable analysis revealed that obesity (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.28–5.73; P = .002) and Charlson comorbidity index score (aHR, 1.20; 95% CI, 1.07–1.35; P = .002) were independent predictors of in-hospital 30-day mortality.ConclusionsObesity was identified as the strongest negative predictor of 30-day in-hospital survival in young adults with COVID-19.

Association of metabolic–bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants

Metabolic-bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy-especially stratified by pre-existing diabetes status-are needed to guide policy and facilitate patient counselling. We compared long-term survival outcomes of severely obese patients who received metabolic-bariatric surgery versus usual care. We did a prespecified one-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. We searched PubMed, Scopus, and MEDLINE (via Ovid) for randomised trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic-bariatric surgery versus non-surgical management of obesity published between inception and Feb 3, 2021. We also searched grey literature by reviewing bibliographies of included studies as well as review articles. Shared-frailty (ie, random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic-bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. We also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling. The study protocol is prospectively registered on PROSPERO, number CRD42020218472. Among 1470 articles identified, 16 matched cohort studies and one prospective controlled trial were included in the analysis. 7712 deaths occurred during 1·2 million patient-years. In the overall population consisting 174 772 participants, metabolic-bariatric surgery was associated with a reduction in hazard rate of death of 49·2% (95% CI 46·3-51·9, p<0·0001) and median life expectancy was 6·1 years (95% CI 5·2-6·9) longer than usual care. In subgroup analyses, both individuals with (hazard ratio 0·409, 95% CI 0·370-0·453, p<0·0001) or without (0·704, 0·588-0·843, p<0·0001) baseline diabetes who underwent metabolic-bariatric surgery had lower rates of all-cause mortality, but the treatment effect was considerably greater for those with diabetes (between-subgroup I2 95·7%, p<0·0001). Median life expectancy was 9·3 years (95% CI 7·1-11·8) longer for patients with diabetes in the surgery group than the non-surgical group, whereas the life expectancy gain was 5·1 years (2·0-9·3) for patients without diabetes. The numbers needed to treat to prevent one additional death over a 10-year time frame were 8·4 (95% CI 7·8-9·1) for adults with diabetes and 29·8 (21·2-56·8) for those without diabetes. Treatment effects did not appear to differ between gastric bypass, banding, and sleeve gastrectomy (I2 3·4%, p=0·36). By leveraging the results of this meta-analysis and other published data, we estimated that every 1·0% increase in metabolic-bariatric surgery utilisation rates among the global pool of metabolic-bariatric candidates with and without diabetes could yield 5·1 million and 6·6 million potential life-years, respectively. Among adults with obesity, metabolic-bariatric surgery is associated with substantially lower all-cause mortality rates and longer life expectancy than usual obesity management. Survival benefits are much more pronounced for people with pre-existing diabetes than those without. None.

Relative survival in adults with new delirium, cerebrovascular events or both after cardiac surgery: A prospective cohort study.

Relative survival in adults with new delirium, cerebrovascular events or both after cardiac surgery: A prospective cohort study.

Older adults with colon cancer are not different from younger ones, but treated differently: Retrospective analysis from single centre.

Decision- making of the treatment of colon cancer for the older patients becomes more complicated in consequence of comorbidities and geriatric syndromes, most importantly frailty. In the present study, we aimed to investigate whether there is a difference between tumour characteristics, treatment choices, and outcomes between the younger and older adults. The patients who were diagnosed with colorectal carcinoma in our centre between 2010 and 2015 included. Clinicopathological features of tumour, treatment choices and survivals of the patients were recorded. Patients were separated into two groups according to their chronological age. The present study included 465 patients, there were 173 patients aged 65 years and older. Clinicopathological features were similar in both groups. Adjuvant chemotherapy was given in similar rates. Whereas combination chemotherapies were preferred in younger patients as first-line therapy, single agents were given to the older group(p-value < 0.001). No significant differences were observed between combination therapy and monotherapy as progression-free and overall survival in older adults(p value > 0.05). It was observed that 53.2% of the older patients was not treated with any biological treatment (p-value < 0.001). Geriatric people are underrepresented in clinical trials,because of the presence of the limitations in the older patients. The results of our study revealed older patients with colon cancer patients underwent surgery less than the younger ones, they recieved monotherapy more frequently as first-line chemotherapy, and less frequently targeted therapy. Their mortality was higher. It was shown that decision-making of colon cancer therapy is influenced by age according to our results.

A French multicentric prospective prognostic cohort with epidemiological, clinical, biological and treatment information to improve knowledge on lymphoma patients: study protocol of the \u201cREal world dAta in LYmphoma and survival in adults\u201d (REALYSA) cohort

BackgroundAge-adjusted lymphoma incidence rates continue to rise in France since the early 80’s, although rates have slowed since 2010 and vary across subtypes. Recent improvements in patient survival in major lymphoma subtypes at population level raise new questions about patient outcomes (i.e. quality of life, long-term sequelae). Epidemiological studies have investigated factors related to lymphoma risk, but few have addressed the extent to which socioeconomic status, social institutional context (i.e. healthcare system), social relationships, environmental context (exposures), individual behaviours (lifestyle) or genetic determinants influence lymphoma outcomes, especially in the general population. Moreover, the knowledge of the disease behaviour mainly obtained from clinical trials data is partly biased because of patient selection.MethodsThe REALYSA (“REal world dAta in LYmphoma and Survival in Adults”) study is a real-life multicentric cohort set up in French areas covered by population-based cancer registries to study the prognostic value of epidemiological, clinical and biological factors with a prospective 9-year follow-up. We aim to include 6000 patients over 4 to 5 years. Adult patients without lymphoma history and newly diagnosed with one of the following 7 lymphoma subtypes (diffuse large B-cell, follicular, marginal zone, mantle cell, Burkitt, Hodgkin, mature T-cell) are invited to participate during a medical consultation with their hematologist. Exclusion criteria are: having already received anti-lymphoma treatment (except pre-phase) and having a documented HIV infection. Patients are treated according to the standard practice in their center. Clinical data, including treatment received, are extracted from patients’ medical records. Patients’ risk factors exposures and other epidemiological data are obtained at baseline by filling out a questionnaire during an interview led by a clinical research assistant. Biological samples are collected at baseline and during treatment. A virtual tumor biobank is constituted for baseline tumor samples. Follow-up data, both clinical and epidemiological, are collected every 6 months in the first 3 years and every year thereafter.DiscussionThis cohort constitutes an innovative platform for clinical, biological, epidemiological and socio-economic research projects and provides an opportunity to improve knowledge on factors associated to outcome of lymphoma patients in real life.Trial registration2018-A01332–53, ClinicalTrials.gov identifier: NCT03869619.

Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia

Standard chemotherapy for first relapse of B-cell acute lymphoblastic leukemia (B-ALL) in children, adolescents, and young adults is associated with high rates of severe toxicities, subsequent relapse, and death, especially for patients with early relapse (high risk) or late relapse with residual disease after reinduction chemotherapy (intermediate risk). Blinatumomab, a bispecific CD3 to CD19 T cell-engaging antibody construct, is efficacious in relapsed/refractory B-ALL and has a favorable toxicity profile. To determine whether substituting blinatumomab for intensive chemotherapy in consolidation therapy would improve survival in children, adolescents, and young adults with high- and intermediate-risk first relapse of B-ALL. This trial was a randomized phase 3 clinical trial conducted by the Children's Oncology Group at 155 hospitals in the US, Canada, Australia, and New Zealand with enrollment from December 2014 to September 2019 and follow-up until September 30, 2020. Eligible patients included those aged 1 to 30 years with B-ALL first relapse, excluding those with Down syndrome, Philadelphia chromosome-positive ALL, prior hematopoietic stem cell transplant, or prior blinatumomab treatment (n = 669). All patients received a 4-week reinduction chemotherapy course, followed by randomized assignment to receive 2 cycles of blinatumomab (n = 105) or 2 cycles of multiagent chemotherapy (n = 103), each followed by transplant. The primary end point was disease-free survival and the secondary end point was overall survival, both from the time of randomization. The threshold for statistical significance was set at a 1-sided P <.025. Among 208 randomized patients (median age, 9 years; 97 [47%] females), 118 (57%) completed the randomized therapy. Randomization was terminated at the recommendation of the data and safety monitoring committee without meeting stopping rules for efficacy or futility; at that point, 80 of 131 planned events occurred. With 2.9 years of median follow-up, 2-year disease-free survival was 54.4% for the blinatumomab group vs 39.0% for the chemotherapy group (hazard ratio for disease progression or mortality, 0.70 [95% CI, 0.47-1.03]); 1-sided P = .03). Two-year overall survival was 71.3% for the blinatumomab group vs 58.4% for the chemotherapy group (hazard ratio for mortality, 0.62 [95% CI, 0.39-0.98]; 1-sided P = .02). Rates of notable serious adverse events included infection (15%), febrile neutropenia (5%), sepsis (2%), and mucositis (1%) for the blinatumomab group and infection (65%), febrile neutropenia (58%), sepsis (27%), and mucositis (28%) for the chemotherapy group. Among children, adolescents, and young adults with high- and intermediate-risk first relapse of B-ALL, postreinduction treatment with blinatumomab compared with chemotherapy, followed by transplant, did not result in a statistically significant difference in disease-free survival. However, study interpretation is limited by early termination with possible underpowering for the primary end point. ClinicalTrials.gov Identifier: NCT02101853.

Acute patient-reported outcomes in B-cell malignancies treated with axicabtagene ciloleucel.

Chimeric antigen receptor T‐cell therapy with axicabtagene ciloleucel (axi‐cel) has considerably improved survival in adults with relapsed/refractory large B‐cell lymphoma. This study reports patient‐reported outcomes (PROs) such as quality of life (QOL) and toxicity in the first 90 days after treatment. Hematologic cancer patients treated with axi‐cel (N = 103, mean age = 61, 39% female) completed SF‐36 or PROMIS‐29 QOL questionnaires prior to treatment and 90 days after. PRO‐Common Terminology Criteria for Adverse Events toxicity items were completed by patients at baseline and 14, 30, 60, and 90 days after treatment. Mixed models examined change in PROs over time. From preinfusion to 90 days later, patients reported improvements in physical functioning, pain, and fatigue (ps < 0.01), but worsening of anxiety (p = 0.02). Patient‐reported toxicities worsened by day 14 with improvement thereafter. The five most severe symptoms at day 14 included fatigue, decreased appetite, dry mouth, diarrhea frequency, and problems with concentration. Results indicate improvement in some domains of QOL over time with transient patient‐reported toxicities.

Increased frequency of heart transplantation, shortened waitlist time and preserved post-transplant survival in adults with congenital heart disease, on the new heart transplant allocation system.

Historically, adult congenital patients have longer waitlist time and worse outcomes on the heart transplant waitlist as well as poorer early post-transplant survival. A new heart transplantation allocation system was implemented in the United States on October 18, 2018. The effect of the new allocation system on adult congenital patients is unknown. Adult congenital patients listed for transplantation between November 1, 2015 and September 30, 2019 registered in the United Network for Organ Sharing were included in the study. October 18, 2018 was used as the limit to distribute listed and transplanted patients into old and new groups. A total of 399 patients were listed for heart transplant only, 284 in the old system and 115 in the new system. Clinical characteristics were similar between both groups. The cumulative incidence of poor outcome on the transplant list was similar in both groups (P=.23), but the cumulative incidence of transplant was higher in the new system group (P<.009) and was associated with a shorter waitlist time. The one-year post-transplant outcome was similar between old and new groups (P=.37). The new allocation system has benefited adult congenital patients with increased cumulative frequency of transplantation without worsening short-term survival after transplantation.

Association of insurance disparities and survival in adults with multiple myeloma: A non-concurrent cohort study

BackgroundMultiple myeloma (MM) accounts for 10 % of all hematological malignancies. As recent advances in MM treatment continue to improve survival rates, socioeconomic barriers need to be identified to ensure equal treatment. This study evaluates the association between insurance status and survival in patients with MM. MethodsThis study analyzed patients with MM from the 2007–2016 Surveillance, Epidemiology, and End Results (SEER) Program database. Insurance status was categorized as uninsured, Medicaid, private insurance, and other insurance. Cancer-specific survival was measured at one- and five-years post diagnosis. ResultsFrom 2007–2016, there were 41,846 patients with MM extracted from the SEER database. Those with private insurance had a higher proportion of participants that identified as married (65.5 %), resided in metropolitan cities (90.1 %), and identified as white (76 %) and non-Hispanic (90.8 %). The uninsured group had the highest proportion of Black participants compared to other insurance groups (37.4 %). After adjustment for age, sex, race, ethnicity, marital status, and residence, the likelihood of five-year survival was significantly lower in those respondents with Medicaid (adjusted (adj) Hazard Ratio (HR): 1.44; 95 % Confidence Interval (CI): 1.36−1.53), when compared with private insurance holders. Those who were uninsured had a 26 % increased mortality hazard than those with private insurance (95 % CI 1.04−1.53). ConclusionAfter adjustment, insurance status can influence the survival of adults with MM. As treatment modalities for MM continue to advance, the insurance status of a patient should not hinder their ability to receive the most effective and timely therapies.

Incident mobility disability, parkinsonism, and mortality in community-dwelling older adults.

Mobility disability and parkinsonism are associated with decreased survival in older adults. This study examined the transition from no motor impairment to mobility disability and parkinsonism and their associations with death. 867 community-dwelling older adults without mobility disability or parkinsonism at baseline were examined annually. Mobility disability was based on annual measured gait speed. Parkinsonism was based on the annual assessment of 26 items from the motor portion of the Unified Parkinson's Disease Rating Scale. A multistate Cox model simultaneously examined the incidences of mobility disability and parkinsonism and their associations with death. Average age at baseline was 75 years old and 318 (37%) died during 10 years of follow-up. Mobility disability was almost 2-fold more common than parkinsonism. Some participants developed mobility disability alone (42%), or parkinsonism alone (5%), while many developed both (41%). Individuals with mobility disability or parkinsonism alone had an increased risk of death, but their risk was less than the risk in individuals with both impairments. The risk of death did not depend on the order in which impairments occurred. The varied patterns of transitions from no motor impairment to motor impairment highlights the heterogeneity of late-life motor impairment and its contribution to survival. Further studies are needed to elucidate the underlying biology of these different transitions and how they might impact survival.

Emergency Thrombolysis During Cardiac Arrest Due to Pulmonary Thromboembolism: Our Experience Over 6 Years.

IntroductionCardiac arrest (CA) is one of the leading causes of death worldwide. Among patients with CA, pulmonary embolism (PE) accounts for approximately 10% of all cases.ObjectiveTo compare the outcomes after cardiopulmonary-cerebral resuscitation (CCPR) with and without thrombolytic therapy (TT) in patients with CA secondary to PE.MethodsWe included patients older than 17 years admitted to our hospital between 2013 and 2017 with a diagnosis of CA with confirmed or highly suspected PE who received CCPR with or without TT. Measures of central tendency were used to depict the data.ResultsThe study comprised 16 patients, 8 of whom received CCPR and thrombolysis with alteplase, whereas the remaining patients received CCPR without TT. The most frequent rhythm of CA in both groups was pulseless electrical activity. Return of spontaneous circulation (ROSC) occurred in 100% of patients who received TT and in 88% of non-thrombolysed patients. The mortality rate of patients who received TT and non-thrombolysed patients at 24 hours was 25% and 50%, respectively. However, at the time of hospital discharge, the mortality was the same in both groups (62%). In patients who received TT, mortality was related to sepsis and hemorrhage whereas in non-thrombolysed patients, mortality was due to myocardial dysfunction.ConclusionIntra-arrest thrombolysis resulted in a higher likelihood of ROSC and a higher 24-hour survival in adults with CA secondary to acute PE. Overall, the survival at hospital discharge was the same in the two groups.

Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics.

The pathogenesis of Tuberculous meningitis (TBM) is poorly understood, but contemporary molecular biology technologies have allowed for recent improvements in our understanding of TBM. For instance, neutrophils appear to play a significant role in the immunopathogenesis of TBM, and either a paucity or an excess of inflammation can be detrimental in TBM. Further, severity of HIV-associated immunosuppression is an important determinant of inflammatory response; patients with the advanced immunosuppression (CD4+ T-cell count of <150cells/μL) having higher CSF neutrophils, greater CSF cytokine concentrations and higher mortality than those with CD4+ T-cell counts > 150 cells/μL. Host genetics may also influence outcomes with LT4AH genotype predicting inflammatory phenotype, steroid responsiveness and survival in Vietnamese adults with TBM. Whist in Indonesia, CSF tryptophan level was a predictor of survival, suggesting tryptophan metabolism may be important in TBM pathogenesis. These varying responses mean that we must consider whether a "one-size-fits-all" approach to anti-bacillary or immunomodulatory treatment in TBM is truly the best way forward. Of course, to allow for proper treatment, early and rapid diagnosis of TBM must occur. Diagnosis has always been a challenge but the field of TB diagnosis is evolving, with sensitivities of at least 70% now possible in less than two hours with GeneXpert MTB/Rif Ultra. In addition, advanced molecular techniques such as CRISPR-MTB and metagenomic next generation sequencing may hold promise for TBM diagnosis. Host-based biomarkers and signatures are being further evaluated in childhood and adult TBM as adjunctive biomarkers as even with improved molecular assays, cases are still missed. A better grasp of host and pathogen behaviour may lead to improved diagnostics, targeted immunotherapy, and possibly biomarker-based, patient-specific treatment regimens.

Disparities in Cancer Survival Among Adolescents and Young Adults: A Population-Based Study of 88 000 Patients.

Adolescents and young adults (AYA, aged 15-39 years) diagnosed with cancer comprise a growing, yet understudied, population. Few studies have examined disparities in cancer survival in underserved and diverse populations of AYA. Using population-based data from the Texas Cancer Registry, we estimated 5-year relative survival of common AYA cancers and examined disparities in survival by race and ethnicity, neighborhood poverty, urban or rural residence, and insurance type. We also used multivariable Cox proportional hazards regression models to examine associations of race or ethnicity, neighborhood poverty, urban or rural residence, and insurance type with all-cause mortality. We identified 55 316 women and 32 740 men diagnosed with invasive cancer at age 15-39 years between January 1, 1995, and December 31, 2016. There were disparities in relative survival by race and ethnicity, poverty, and insurance for many cancer types. Racial and ethnic disparities in survival for men with non-Hodgkin lymphoma (74.5% [95% confidence interval (CI) = 72.1% to 76.7%] White vs 57.0% [95% CI = 51.9% to 61.8%] Black) and acute lymphocytic leukemia (66.5% [95% CI = 61.4% to 71.0%] White vs 44.4% [95% CI = 39.9% to 48.8%] Hispanic) were striking, and disparities remained even for cancers with excellent prognosis, such as testicular cancer (96.6% [95% CI = 95.9% to 97.2%] White vs 88.7% [95% CI = 82.4% to 92.8%] Black). In adjusted analysis, being Black or Hispanic, living in high-poverty neighborhoods, and having Medicaid, other government insurance, or no insurance at diagnosis were associated with all-cause mortality in both women and men (all 2-sided P < .01). Our study adds urgency to well-documented disparities in cancer survival in older adults by demonstrating persistent differences in relative survival and all-cause mortality in AYAs. Findings point to several areas of future research to address disparities in this unique population of cancer patients.

Investigation of the protective effect of acetazolamide and SLC-0111 on carbon tetrachloride-induced toxicity in fruit fly.

Sulfonamide-based compounds in the development of drugs used in cancer treatment have been started to be investigated recently. In the current work, it was determined the protective effect of Acetazolamide (AAZ) and SLC-0111 on carbon tetrachloride-induced toxicity in the fruit fly (Drosophila melanogaster). AAZ and SLC-0111 were used as a nonselective and selective inhibitor of carbonic anhydrase isozymes, respectively, to compare the selectivity effect of drugs on toxicity. The experimental toxicity was created by carbon tetrachloride (CCl4) that causes tissue damage to the first stage larvae of fruit fly and used as a model organism. The effect of AAZ and SLC-0111 on toxicity of insect survival, sex ratio, longevity and some biochemical parameters such as Malondialdehyde-MDA content, Superoxide dismutase-SOD and Glutathione-S-transferase-GST activity were tested. According to the data obtained, feeding of insects with AAZ and SLC-0111 (2.5 and 10 mM, respectively) affected their survival and development positively against the toxicity induced by CCl4. Compared to the control group, GST and SOD activity was higher in pups and adults (SLC-0111 < AAZ). Because of this study, SLC-0111 is thought to be useful in protecting against the harmful effects of reactive oxygen species.