Early immune reconstitution as predictor for outcomes after allogeneic hematopoietic cell transplant; a tri-institutional analysis

Background aimsCD4 immune reconstitution (IR) after allogeneic hematopoietic cell transplant (allo-HCT) correlates with lower non-relapse mortality (NRM), but its impact on leukemia relapse remains less clear, especially in children. We studied the correlation between IR of lymphocyte subsets and HCT outcomes in a large cohort of children/young adults with hematological malignancies.MethodsWe retrospectively analyzed CD4, CD8, B-cell and natural killer (NK) cell reconstitution in patients after first allo-HCT for a hematological malignancy at three large academic institutions (n = 503; period 2008–2019). We used Cox proportional hazard and Fine–Gray competing risk models, martingale residual plots and maximally selected log-rank statistics to assess the impact of IR on outcomes.ResultsAchieving CD4 >50 and/or B cells >25 cells/μL before day 100 after allo-HCT was a predictor of lower NRM (CD4 IR: hazard ratio [HR] 0.26, 95% confidence interval [CI] 0.11–0.62, P = 0.002; CD4 and B cell IR: HR 0.06, 95% CI 0.03–0.16, P < 0.001), acute graft-versus-host disease (GVHD) (CD4 and B cell IR: HR 0.02, 95% CI 0.01–0.04, P < 0.001) and chronic GVHD (CD4 and B cell IR: HR 0.16, 95% CI 0.05–0.49, P = 0.001) in the full cohort, and of lower risk of relapse (CD4 and B cell IR: HR 0.24, 95% CI 0.06–0.92, P = 0.038) in the acute myeloid leukemia subgroup. No correlation between CD8 and NK-cell IR and relapse or NRM was found.ConclusionsCD4 and B-cell IR was associated with clinically significant lower NRM, GVHD and, in patients with acute myeloid leukemia, disease relapse. CD8 and NK-cell IR was neither associated with relapse nor NRM. If confirmed in other cohorts, these results can be easily implemented for risk stratification and clinical decision making.     

Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort – Differential effects by tumour subtype,NAT2 status,BMI and alcohol intake

BackgroundInconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking.MethodsWe used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50–74 and diagnosed with invasive tumours 2001–2005 in Germany, with a median follow-up time of 6 years. The effect of pre-diagnostic smoking behaviour on mortality outcomes and risk of recurrence was investigated using delayed entry Cox regression analysis. Differential effects according to N-acetyltransferase (NAT2) status, BMI, alcohol consumption, and tumour subtypes were assessed.ResultsOverall, smoking at time of breast cancer diagnosis versus never/former smoking was non-significantly associated with increased breast cancer-specific mortality and risk of recurrence (HR 1.23, 95% CI 0.93–1.64, and HR 1.29, 95% CI 0.95–1.75, respectively). Associations were consistently stronger in NAT2 slow than in fast acetylators for all mortality outcomes. Breast cancer-specific mortality was significantly increased in smokers with NAT2 slow acetylating status (HR 1.77, 95% CI 1.13–2.79) but not in those with fast acetylating status (HR 1.09, 95% CI 0.60–1.98; P_{heterogeneity} = 0.19). Smoking was associated with significantly poorer outcomes for triple negative and luminal A-like tumours (e.g. all-cause mortality: HR 1.93, 95% CI 1.02–3.65, and HR 2.08, 95% CI 1.40–3.10, respectively). Risk of recurrence was significantly increased for women with HER2 positive tumours (HR 3.64, 95% CI 1.22–10.8). There was significant heterogeneity by BMI for non-breast cancer-specific mortality (<25 kg/m²: HR 2.52, 95% CI 1.52–4.15 vs. ≥25 kg/m²: HR 0.94, 95% CI 0.38–2.36; P_{heterogeneity} = 0.04).ConclusionThe harmful effects of smoking may be particularly relevant for certain subgroups of breast cancer patients. This may include patients with NAT2 slow acetylation status or with tumour subtypes other than luminal B, such as luminal A tumours who usually have a rather good prognosis. Emphasis on smoking cessation programmes for all cancer patients should be strengthened.     

Early CD4+ T cell reconstitution as predictor of outcomes after allogeneic hematopoietic cell transplantation

Background: An association between early CD4+ T cell immune reconstitution (CD4+ IR) and survival after T-replete allogeneic hematopoietic cell transplantation (HCT) has been previously reported. Here we report validation of this relationship in a separate cohort that included recipients of ex vivo T-cell-depleted (TCD) HCT. We studied the relationship between CD4+ IR and clinical outcomes.Methods: A retrospective analysis of children/young adults receiving their first allogeneic HCT for any indication between January 2008 and December 2017 was performed. We related early CD4+ IR (defined as achieving >50 CD4+ T cells/µL on two consecutive measures within 100 days of HCT) to overall survival (OS), relapse, non-relapse mortality (NRM), event-free survival (EFS) and acute graft-versus-host disease (aGVHD). Fine and Gray competing risk models and Cox proportional hazard models were used.Results: In this analysis, 315 patients with a median age of 10.4 years (interquartile range 5.0–16.5 years) were included. The cumulative incidence of CD4+ IR at 100 days was 66.7% in the entire cohort, 54.7% in TCD (N = 208, hazard ratio [HR] 0.47, P < 0.001), 90.0% in uCB (N = 40) and 89.6% in T-replete (N = 47) HCT recipients. In multi-variate analyses, not achieving early CD4+ IR was a predictor of inferior OS (HR 2.35, 95% confidence interval [CI] 1.46–3.79, P < 0.001) and EFS (HR 1.80, 95% CI 1.20–2.69, P = 0.004) and increased NRM (HR 6.58, 95% CI 2.82–15.38, P < 0.001). No impact of CD4+ IR on relapse or aGVHD was found. Within the TCD group, similar associations were observed.Conclusion: In this HCT cohort, including recipients of TCD HCT, we confirmed that early CD4+ IR was an excellent predictor of outcomes. Finding strategies to predict or improve CD4+ IR may influence outcomes.     

Effects of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: A real-world study

BackgroundTo evaluate the value of locoregional radiotherapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (dmNPC) and identify predictive factors for additional LRRT after palliative chemotherapy (PCT).MethodsOverall survival (OS) was the primary endpoint. Patients who underwent PCT and LRRT were categorized as the PCT+LRRT group; patients who only received palliative chemotherapy were categorized as the PCT group. Oligometastatic diseases (OMD) was defined as ≤5 metastatic lesions and ≤2 metastatic organs.ResultsA total of 168 patients were included for this study. The median OS of patients in the PCT+LRRT group was significantly higher than those in the PCT group (57 months vs. 22 months, P<0.001). Multivariate analyses (MVA) showed that LRRT (HR=0.533, 95% CI: 0.319–0.889, P = 0.016) and OMD (HR=0.548, 95% CI: 0.331–0.907, P = 0.019) were independent prognostic factors for dmNPC. Furthermore, Kaplan–Meier analyses showed that the 3-year OS of patients who received LRRT was significantly better than those who did not receive LRRT in the OMD subgroup (66.3% vs. 25.2%, P<0.001). While, the 3-year OS of patients who received LRRT and without LRRT was no different in the polymetastatic disease (PMD) subgroup (38.9% vs.11.5%, P = 0.115). MVA showed that LRRT was a favorable prognosticator in the OMD subgroup (HR=0.308, 95% CI: 0.159–0.598; P<0.001), and not a favorable prognosticator in the PMD subgroup (HR=0.510, 95% CI: 0.256–1.014, P = 0.055).ConclusionsLRRT has the potential to prolong OS in NPC patients with de novo OMD. These results suggest that OMD is a potential indicator for filtering beneficiaries from LRRT.     

Malignant pleural mesothelioma incidence and survival in the Republic of Ireland 1994–2009

ObjectiveMalignant pleural mesothelioma (MPM) is a rare malignancy associated with exposure to asbestos. The protracted latent period of MPM means that its incidence has continued to rise across Europe after the introduction of restrictions on asbestos use. In order to obtain a clearer indication of trends in the Republic of Ireland (ROI), incidence and survival were assessed based on all MPM cases reported since the establishment of the National Cancer Registry of Ireland (NCR).MethodsNCR recorded 337 MPM diagnoses in the ROI during 1994–2009. Survival was assessed for all cases diagnosed with adequate follow-up (n = 330). Crude and European age-standardized incidence rates were calculated for all cases and for 4-year periods. A Cox model of observed (all-cause) survival was used to generate hazard ratios for the effect of: gender; age at diagnosis; diagnosis cohort; region of residence; histological type; and tumour stage. Single P-values for the variables indicated were calculated using either a stratified log-rank test or stratified trend test.ResultsOver the study period the age-standardized MPM incidence in the ROI rose from 4.98 cases per million (cpm) to 7.24 cpm. The 1-year survival rate for all MPM cases was 29.6% (CI 24.7–34.6%). Excess mortality risk was associated with age at diagnosis (75–89 yrs vs. 55–64 yrs, HR 1.88, 95% CI 1.35–2.63, P < 0.001) and tumour stage (III vs. I HR 1.57, 95% CI 1.00–2.48, P < 0.05; IV vs. I HR 1.55, 95% CI 1.08–2.21, P < 0.05). Age showed a significant survival trend (P < 0.001) but tumour stage did not (P = 0.150). There was significant heterogeneity between the survival of patients resident in different regions (P = 0.027).ConclusionMPM incidence and mortality continued to rise in the ROI after the restrictions on asbestos use and the predictors of survival detected in this study are broadly consistent with those identified for other countries.     

Effects of stem cells on non-ischemic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials

Background aimsTo assess the impacts of stem cell therapy on clinical outcomes in patients with non-ischemic cardiomyopathy (NICM). The effect of stem cell therapy on prognosis is unclear and controversial.MethodsThe authors performed a systematic review and meta-analysis of the effects of autologous stem cell transplantation in patients with NICM on a composite outcome of all-cause mortality and heart transplantation, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), New York Heart Association (NYHA) classification, 6-minute walk test (6-MWT) distance and serum brain natriuretic peptide (BNP) level, considering studies published before March 19, 2020.ResultsTwelve trials with 623 subjects met inclusion criteria. Compared with the control group, stem cell therapy improved LVEF (weighted mean difference [WMD], 4.08%, 95% confidence interval [CI], 1.93–6.23, P = 0.0002) and 6-MWT distance (WMD, 101.49 m, 95% CI, 45.62–157.35, P = 0.0004) and reduced BNP level (–294.94 pg/mL, 95% CI, –383.97 to –205.90, P < 0.00001) and NYHA classification (–0.70, 95% CI, –0.98 to –0.43, P < 0.00001). However, LVEDD showed no significant difference between the two groups (WMD, –0.09 cm, 95% CI, –0.23 to 0.06, P = 0.25). In 10 studies (535 subjects) employing the intracoronary route for cell delivery, mortality and heart transplantation were decreased (risk ratio [RR], 0.73, 95% CI, 0.52–1.00, P = 0.05). Furthermore, in four studies (248 subjects) with peripheral CD34+ cells, either all-cause mortality (RR, 0.44, 95% CI, 0.23–0.86, P = 0.02) or mortality and heart transplantation (RR, 0.45, 95% CI, 0.27–0.77, P = 0.003) improved in the treatment group compared with the control. The trial sequential analysis suggested the information size of LVEF, 6-WMT and BNP has been adequate for evidencing the benefits of stem cells on NICM. However, to determine the potential survival benefit, more clinical data are required to make the statistical significance in meta-analysis more conclusive.ConclusionsThis meta-analysis demonstrates that stem cell therapy may improve survival, exercise capacity and cardiac ejection fraction in NICM, which suggests that stem cells are a promising option for NICM treatment.     

Advantages of peripheral blood stem cells from unrelated donors versus bone marrow transplants in outcomes of adult acute myeloid leukemia patients

Background aimsIn allogeneic stem cell transplantation, unrelated donors are chosen in cases where appropriate related donors are not available. Peripheral blood stem cells (PBSCs) are more often selected as a graft source than bone marrow (BM). However, the prognostic benefits of PBSCs versus BM transplants from unrelated donors have not been carefully examined in patients with acute myeloid leukemia (AML). This study compared outcomes of adult AML patients who underwent unrelated PBSC and BM transplantation, evaluating post-transplant complications, including engraftment, graft-versus-host disease (GVHD) and infections, and determined subgroups of patients who are most likely to benefit from unrelated PBSCs compared with BM transplants.MethodsThe authors analyzed 2962 adult AML patients who underwent unrelated PBSC or BM transplants between 2011 and 2018 (221 PBSC and 2741 BM) using the Japanese nationwide registry database, in which graft source selection is not skewed toward PBSCs.ResultsIn 49.7% of patients, disease status at transplantation was first complete remission (CR1). In 57.1% of cases, HLA-matched donors were selected. Myeloablative conditioning was performed in 75.1% of cases, and anti-thymocyte globulin (ATG) was added to conditioning in 10.5%. Multivariate analyses showed a trend toward favorable non-relapse mortality (NRM) in PBSC recipients compared with BM recipients (hazard ratio [HR], 0.731, P = 0.096), whereas overall survival (OS) (HR, 0.959, P = 0.230) and disease-free survival (DFS) (HR, 0.868, P = 0.221) were comparable between PBSC and BM recipients. Although the rate of chronic GVHD (cGVHD) was significantly higher in PBSC patients (HR, 1.367, P = 0.016), NRM was not increased, mainly as a result of significantly reduced risk of bacterial infections (HR, 0.618, P = 0.010), reflecting more prompt engraftments in PBSC recipients. Subgroup analyses revealed that PBSC transplantation was advantageous in patients transplanted at CR1 and in those without ATG use. PBSC recipients experienced significantly better OS and/or DFS compared with BM recipients in this patient group.ConclusionsThe authors' results confirmed the overall safety of unrelated PBSC transplantation for adult AML patients and suggested an advantage of PBSCs, especially for those in CR1. Further optimization of the prophylactic strategy for cGVHD is required to improve the overall outcome in transplantation from unrelated PBSC donors.     

The predictive efficacy of tumor mutation burden in immunotherapy across multiple cancer types: A meta-analysis and bioinformatics analysis

PurposeTo explore the predictive efficacy of tumor mutation burden (TMB) as a potential biomarker for cancer patients treated with Immune checkpoint inhibitors (ICIs).MethodsWe systematically searched PubMed, Cochrane Library, Embase and Web of Science for clinical studies (published between Jan 1, 2014 and Aug 30, 2021) comparing immunotherapy patients with high TMB to patients with low TMB. Our main endpoints were objective response rate (ORR), durable clinical benefit (DCB), overall survival (OS) and progress-free Survival (PFS). Moreover, we downloaded simple nucleotide variation (SNV) data of 33 major cancer types from the TCGA database as non-ICIs group, and compared the high TMB patients’ OS between the non-ICIs group and meta-analysis results.ResultsOf 10,450 identified studies, 41 were eligible and were included in our analysis (7713 participants). Compared with low TMB patients receiving ICIs, high TMB yielded a better ORR (RR = 2.73; 95% CI: 2.31–3.22; P = 0.043) and DCB (RR = 1.93; 95% CI: 1.64–2.28; P = 0.356), and a significantly increased OS (HR =0.24; 95% CI: 0.21–0.28; P < 0.001) and PFS (HR = 0.38; 95% CI: 0.34–0.42; P < 0.001). Furthermore, compared with non-ICIs group from the TCGA database, immunotherapy can improve OS in some cancer types with high TMB and better prognosis, including colorectal cancer, gastric cancer, lung cancer, melanoma and pan-cancer.ConclusionTMB is a promising therapeutic and prognostic biomarker for immunotherapy, which indicates a better ORR, DCB, OS and PFS. If there is a standard for TMB assessment and cut-off, it could improve the management of different cancers.     

Male-origin microchimerism and endometrial cancer: A prospective case-cohort study

BackgroundMany women carry male cells of presumed fetal origin–so-called male-origin microchimerism (MOM)–in their circulation and tissues. Studies have found reduced risks of hormone dependent cancers, including breast and ovarian cancer, among MOM-positive women. The aim of this study was to investigate the association between MOM and endometrial cancer.MethodsWe designed a prospective case-cohort study including 76 cases and 505 controls from the Diet, Cancer and Health cohort aged 50–64 years and cancer-free at enrolment in 1993–1997. We analyzed blood samples for the presence of Y-chromosome (DYS14). We examined the association between MOM and endometrial cancer in weighted Cox regression models. As a negative control outcome, we studied the association between MOM and injuries to test for spurious associations.ResultsWe detected MOM in 65.9% controls and 54.0% cases. While we observed no overall association between MOM and endometrial cancer (HR=0.73, 95% CI: 0.47–1.15), we found a borderline significantly reduced rate of Type 1 endometrial cancer (HR=0.66, 95% CI: 0.39–1.00), but not other types of endometrial cancers (HR=1.00, 95% CI: 0.35–2.90). The reduced rate was not modified by hormonal exposure (P = 0.79). We found no association between MOM and risk of injuries (HR=0.96, 95% CI: 95% CI: 0.78–1.21).ConclusionsOur study suggests that MOM is inversely associated with Type 1 endometrial cancer, without evidence of an interaction with hormonal exposure. We encourage future research to confirm our findings.     

Cancer risk associated with the use of valsartan in Korea: A nationwide cohort study

BackgroundDespite valsartan’s widespread use, few studies have explored its potential carcinogenicity. We evaluated the association between valsartan and cancer.MethodsWe conducted a retrospective cohort study using data from 2002 to 2015 gathered from the National Health Insurance database. Patients with hypertension aged ≥ 30 who used valsartan or other angiotensin II receptor blockers (ARBs) were included. Eligible patients were those with no prior history of the use of any ARBs, diagnosis of cancer, or organ transplantation in the 4 years predating their first use of the drugs of interest. The primary and secondary outcomes included the occurrence of all cancers and site-specific solid cancers, respectively. After applying propensity score (PS) matching, Cox regression was used to calculate the hazard ratios (HRs) and 95 % confidence intervals (CIs).ResultsA total of 1,550,734 individuals were identified as new users of valsartan or other ARBs. Of the 153,047 valsartan users, 16,047 were diagnosed with cancer. No increased risk of overall cancer was observed in valsartan users as compared to other ARB users (aHR = 1.00; 95 % CI, 0.98–1.02). Valsartan was, however, associated with a slightly elevated risk of liver (aHR = 1.09; 95 % CI, 1.01–1.16) and kidney cancer (aHR = 1.11; 95 % CI, 1.02–1.22).ConclusionCompared with other ARBs, valsartan did not increase the risk of overall cancer. A slightly increased risk for some solid cancers was associated with valsartan use, though the absolute rate difference was small.     

Systematic review and meta-analysis of the association between bridging therapy and outcomes of chimeric antigen receptor T cell therapy in patients with large B cell lymphoma

BackgroundThe existing evidence about the impact of bridging therapy (BT) on chimeric antigen receptor (CAR)-T cell therapy in patients with large B cell lymphoma (LBCL) is conflicting. Therefore, we reviewed all available evidence to examine the association between BT and CAR-T therapy outcomes by systematic review and meta-analysis approach.MethodsTwo reviewers independently searched Embase, PubMed, Web of Science, and Cochrane library to identify all records that described BT for LBCL treated with CAR-T. We then applied a fixed- or random-effects meta-analysis to estimate the pooled hazard ratios (HRs) and rate ratio (RRs) for efficacy and safety endpoints and assessed differences across various BT modalities. The Newcastle-Ottawa Scale was used to evaluate study quality.ResultsTwenty-six reports from 24 studies involving 2014 patients were included in the analysis. Pooled results showed that patients requiring BT had significantly worse 1-year overall survival rate (RR = 0.76, 95% confidence interval [CI] 0.68–0.85, P < 0.001), 1-year progression-free survival rate (RR = 0.71, 95% CI 0.60–0.85, P < 0.001), progression-free survival (HR = 1.35, 95% CI 1.07–1.69, P = 0.01), overall response rate (RR = 0.88, 95% CI 0.81–0.95, P = 0.001), complete response rate (RR = 0.78, 95% CI 0.65–0.93, P = 0.005), and grade ≥3 immune effector cell-associated neurotoxicity syndrome (RR = 1.43, 95% CI 1.10–1.87, P = 0.007), and tended to have poorer overall survival (HR = 1.42, 95% CI 0.99–2.02, P = 0.056) and grade ≥3 cytokine release syndrome (RR = 1.59, 95% CI 0.92–2.75, P = 0.096). Prolonged cytopenias were the common toxicity event associated with BT. Radiotherapy may serve as a promising BT option that can provide safe and effective disease control for patients with LBCL before CAR-T infusion. The inconsistency of patient baselines in the current study hindered further comparisons between different BT modalities. Most of the available evidence was rated as low quality because of concerns over low comparability.ConclusionBT appears to be associated with comparatively poor efficacy and safety outcomes after CAR-T infusion. However, due to the considerable heterogeneity between the BT and non-BT cohorts at disease baseline, no definitive conclusions can be made for the true impact of BT on CAR-T until further randomized studies are conducted.     

Early lymphocyte reconstitution is associated with improved transplant outcome after cord blood transplantation

Background aimsPrevious studies have shown that rapid recovery of the absolute lymphocyte count (ALC) is associated with improved transplant outcomes after related and unrelated donor allogeneic stem cell transplantation (allo-SCT). No consistent association has been reported between lymphocyte recovery and transplant outcome after cord blood transplantation (CBT)MethodsWe reviewed the records of 40 consecutive CBT patients at our institution to determine the impact of lymphocyte recovery on transplant outcomeResultsThe majority of patients (83%) received CBT for hematologic malignancies. Patients with ALC ≥150/μL at 30 days post-CBT had decreased non-relapse mortality (NRM) (P = 0.011) and improved survival (P = 0.013) compared with ALC < 150/μL. Patients with ALC < 100/μL at 30 days post-CBT had a significantly higher rate of graft failure than those with ALC ≥100/μL (four of 10 versus one of 29; P = 0.011). ALC was positively correlated with the nucleated cell dose and inversely correlated with the patient's age. There was no relationship between disease risk, type of conditioning regimen, anti-thymocyte globulin and number of cord units on ALC recoveryConclusionsOur results indicate that ALC 30 days post-CBT is a surrogate for engraftment, and that low ALC (<150/μL) identifies an ‘at-risk’ population of patients after CBT. Studies are needed to determine ways to increase ALC cell numbers post-CBT, including ex vivo-expanded natural killer cells using adoptive immunotherapy, which might improve outcome after CBT.     

Preoperative red blood cell distribution width as an independent prognostic factor in metastatic renal cell carcinoma

ObjectiveThis study aimed to explore the prognostic value of preoperative red blood cell distribution width (RDW) in patients with metastatic renal cell carcinoma (mRCC).MethodsClinicopathological data of 230 patients with mRCC treated at the First Affiliated Hospital of Chongqing Medical University and the Chinese PLA General Hospital from January 2008 to December 2018 were retrospectively analyzed. Patients were stratified according to the optimal cut-off value of RDW calculated using X-tile software. The prognostic value of RDW was analyzed using the Kaplan-Meier curve with log-rank test and univariate and multivariate Cox proportional hazards models.ResultsA total of 230 patients were included. The optimal cut-off value of RDW obtained using X-tile software was 13.1%. The median Progression-free survival (PFS) and Overall survival (OS) of all populations were 12.06 months (IQR: 4.73–36.9) and 32.20 months (IQR: 13.73–69.46), respectively. Kaplan–Meier curves showed that patients with high RDW had worse PFS and OS than those with low RDW (median PFS of 9.7 months vs. 17.9 months, P = 0.002, and median OS of 27.8 months vs. 45.1 months, P = 0.012, respectively). Multivariate analysis showed that RDW was an independent risk factor for PFS (HR: 1.505; 95% CI: 1.111–2.037; P = 0.008) and OS (HR: 1.626; 95% CI: 1.164–2.272; P = 0.004) in mRCC after cytoreductive nephrectomy.ConclusionPreoperative RDW was independently associated with PFS and OS in patients with mRCC and may be a potential predictor of survival outcomes in mRCC.     

Factors Predicting Long-term Estimated Glomerular Filtration Rate Decrease,a Reliable Indicator of Renal Function After Adrenalectomy in Primary Aldosteronism

ObjectiveThe long-term decrease in estimated glomerular filtration rate (eGFR) in patients with primary aldosteronism (PA) after adrenalectomy may be influenced by multiple preoperative factors. The present study aimed to provide a systematic review and meta-analysis of these factors.MethodsA systematic literature search was conducted to determine eligible observational studies on the possible association between preoperative factors and postoperative long-term eGFR decrease in patients with PA using PubMed, Web of Science, Embase, and Cochrane Library databases.ResultsA total of 8 relevant studies with 1159 patients were included. Old age (odds ratio [OR] = 1.05, 95% CI: 1.02-1.09, P = .001), high systolic blood pressure (OR = 1.05, 95% CI: 1.01-1.09, P = .01), baseline hypokalemia (OR = 0.08, 95% CI: 0.02-0.30, P < .001), and low eGFR (OR = 0.92, 95% CI: 0.87-0.97, P = .001) presented a strong association with long-term eGFR decrease after adrenalectomy.ConclusionWe provide evidence that old age, high systolic blood pressure, baseline hypokalemia, and low eGFR are associated with an increased risk of postoperative long-term eGFR decrease in patients with PA postoperatively. More attention should be given to the above factors for the timely prevention and management of renal impairment.     

Tasa de filtración glomerular estimada y mortalidad posterior al alta en una unidad geriátrica de agudos

ObjectiveTo determine the relationship between estimated glomerular filtration rate (eGFR) and mortality in a retrospective cohort of older adults admitted to an acute care for the elderly (ACE) unit.Materials and methodsThe study included 1,678 patients aged 60 years and over admitted to an AEC, in Cali, Colombia, from 2012 to 2015, and followed- up until 2016. The primary outcome was mortality. Renal function (eGFR) was estimated using Modification of Diet in Renal Disease Study (MDRD-4) equation. The renal function was grouped according to the eGFR (ml/min/1.73 m²) as follows: slightly decreased (≥ 60), moderately decreased (30-59), and severely decreased (< 30). Bivariate survival and multivariate Cox regression analyses were performed.ResultsIn the univariate analysis, patients with severely decreased eGFR had higher mortality than those with a higher eGFR (P = .046). In the group with severely decreased eGFR, survival was lower in the functionally dependent group (Barthel index [IB] < 60) than in the independent group (IB ≥ 60) (log rank test; P = .001). In the multivariate analysis, there was a significant increase in the risk of death in the elderly with severely decreased eGFR (< 30) compared with slightly decreased eGFR (≥ 60) (hazard ratio [HR], 1.44; 95% confidence interval [CI]; 1.02-2.05, P = .039). There was also a significant increase in the risk of death in the dependent elderly compared to the independent ones [HR 1.72; 95% CI; 1.26-2.34, P = .000], those who had the high morbidity (≥ 4) with low albumin (< 3.2 g/dL) compared with those with low morbidity (0-3) and high albumin (≥ 3.2) [HR 1.77; 95% CI; 1.18-2.65, P = .005], and in those with a high (16-102 mg/dL) C-reactive protein (CRP) compared with those with low CRP (0-15) [HR 1.42; 95% CI; 1.01-2.01, P = .043].ConclusionsThe risk of mortality after hospital admission to an AEC unit is greater in patients with eGFR < 30. Poor functional status performance, high comorbidity, low plasma albumin, and increased inflammation markers are additional prognostic factors to be taken into account. The improvement in the functional status could improve the survival after hospitalisation.     

Red meat and fruit intake is prognostic among patients with localized cutaneous melanomas more than 1 mm thick

BackgroundAs the 10-year mortality for localized cutaneous melanoma more than 1.00 mm thick approaches 40% following complete resection, non-therapeutic interventions that can supplement recommended active surveillance are needed. Although guidelines recommending nutrition, physical activity and tobacco cessation for cancer survivors have been published, data describing their associations with melanoma survivorship are lacking.MethodsAnalysis of modifiable lifestyle behaviors collected on the 249 cases with melanomas more than 1.00 mm thick enrolled in the Connecticut Case–Control Study of Skin Self-Examination study was conducted. Independent associations with melanoma-specific survival were evaluated through Cox proportional hazards modeling adjusting for age, gender, Breslow thickness, ulceration and the presence of microsatellites. Independently significant variables were then combined into a single model and backwards elimination was employed until all remaining variables were significant at p < 0.05.ResultsFollowing adjustment for age, Breslow thickness and anatomic site of the index melanoma, daily fruit consumption was associated with improved melanoma-specific survival (HR = 0.54; 95% CI: 0.34–0.86) whereas at least weekly red meat consumption was associated with worse outcomes (HR = 1.84; 95% CI: 1.02–3.30). Natural red (HR = 0.44; 95% CI: 0.22–0.88) or blond (HR = 0.52; 95% CI: 0.29–0.94) hair were also favorably prognostic. Higher fish consumption was of borderline significance for improved survival only when considered independently (HR = 0.65; 95% CI: 0.40–1.05); no association was seen following adjustment for red meat and fruit consumption (p > 0.10).ConclusionsDietary choices at the time of diagnosis are associated with melanoma-specific survival in patients with melanomas more than 1.00 mm thick. Further validation of our findings in larger cohorts with repeated post-diagnostic measures is warranted to further evaluate whether dietary modification during the survivorship period can improve melanoma-specific survival.     

Antihypertensive medications and survival in patients with cancer: A population-based retrospective cohort study

Background: The association between antihypertensive medications and survival in cancer patients remains unclear. Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients. Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n = 4241), colorectal (n = 3967), breast (n = 4019) or prostate (n = 3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04–1.44) and lung cancer (HR: 1.11, 95% CI: 1.03–1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02–1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01–1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15–1.42), and prostate (HR 1.41, 1.2–1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64–0.98). Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.     

The prognostic value of circulating tumor DNA in patients with melanoma: A systematic review and meta-analysis

BackgroundCirculating tumor DNA (ctDNA) has been investigated as a potential prognostic biomarker to evaluate the therapeutic efficacy and disease progression in melanoma patients, yet results remain inconclusive. The purpose of this study was to illustrate the prognostic value of ctDNA in melanoma.ObjectivesTo describe the clinical prognostic value of ctDNA for melanoma patients.MethodsSearched for eligible articles from Pubmed, Web of Science and Embase. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ctDNA at baseline or during treatment and overall survival (OS) and progression-free survival (PFS).ResultsA total of 9 articles were obtained, involving 617 melanoma patients. The pooled HRs revealed that compared with baseline undetectable ctDNA patients, detectable ctDNA was highly correlated with poor OS (HR 2.91, 95% CI: 2.22–3.82; p < 0.001) and PFS (HR 2.75, 95% CI: 1.98–3.83; p < 0.001). A meta-analysis of these adjusted HRs was performed and confirmed that ctDNA collected at baseline was associated with poorer OS/PFS (OS: HR 3.00, 95% CI 2.19–4.11, p < 0.001/PFS: HR 2.68, 95% CI 1.77–4.06, p < 0.001). During treatment, a significant association was shown between ctDNA and poorer OS/PFS (OS: HR 6.26, 95% CI 2.48–15.80, p < 0.001; PFS: HR 4.93, 95% CI 2.36–10.33, p < 0.001).ConclusionInvestigation and application of ctDNA will improve "liquid biopsy" and play a role in early prediction, monitoring disease progression and precise adjusting treatment strategies in melanoma patients.     

Kanglaite injection plus platinum-based chemotherapy for stage III/IV non-small cell lung cancer: A meta-analysis of 27 RCTs

BackgroundKanglaite injection (KLT) is a broad-spectrum anti-tumor drug, which is extracted from the seeds of the Chinese medicinal herb Coix lacryma-jobi, and has been widely used for the treatment of advanced lung cancer.PurposeTo evaluate the combined effects of Kanglaite injection plus platinum-based chemotherapy (PBC) on patients with stage III/IV non-small cell lung cancer (NSCLC).Study designA systematic review and meta-analysis of randomized clinical trials (RCTs).Materials and methodsTwelve databases were searched from their inceptions until July 05, 2019. All the RCTs comparing the efficacy and safety of Kanglaite injection plus PBC versus PBC alone were selected. Analyses were performed using Review Manager 5.3, Comprehensive Meta-Analysis 3.0 and Trial Sequential Analysis (TSA). Disease control rate (DCR) was defined as the primary endpoint, objective response rate (ORR), survival rate, quality of life (QOL), cellular immunity function, and toxicities were defined as the secondary endpoints.ResultsTwenty-seven RCTs recruiting 2,243 patients with stage III/IV NSCLC were included. The results showed that, compared with PBC alone, Kanglaite injection plus PBC improved DCR (RR = 1.20, 95% CI 1.15–1.26, p < 0.00001), ORR (RR = 1.45, 95% CI 1.31–1.60, p < 0.00001), 1-year survival rate (RR = 1.20, 95% CI 1.02–1.43, p = 0.03), QOL (RR = 1.32, 95% CI 1.25–1.40, p < 0.00001), CD4⁺ T cells (WMD = 4.86, 95% CI 4.00–5.73, p < 0.00001), CD4⁺/CD8⁺ ratio (WMD = 0.19, 95% CI 0.07–0.31, p < 0.002), and reduced severe toxicities by 59% (RR = 0.41, 95% CI 0.33–0.51, p < 0.00001). Most results were robust and the quality of evidence was from moderate to low.ConclusionsKanglaite injection in combination with PBC showed significantly higher efficacy than PBC alone in the treatment of stage III/IV NSCLC. Moreover, the combination therapy can improve cellular immunity and attenuate the severe toxicities caused by chemotherapy. However, high-quality RCTs are warranted to further assess the effects of the combined therapy.     

The relation between resting heart rate and cancer incidence,cancer mortality and all-cause mortality in patients with manifest vascular disease

BackgroundPrevious studies suggest that elevated resting heart rate (RHR) is related to an increased risk of cancer mortality. The aim of this study was to evaluate the relation between RHR and cancer incidence and mortality in patients with vascular disease.MethodsPatients with manifest vascular disease (n = 6007) were prospectively followed-up for cancer incidence and mortality. At baseline, RHR was obtained from an electrocardiogram. The relation between RHR and cancer incidence, cancer mortality and total mortality was assessed using competing risks models.ResultsDuring a median follow-up of 6.0 years (interquartile range: 3.1–9.3) 491 patients (8%) were diagnosed with cancer and 907 (15%) patients died, 248 (27%) died from cancer. After adjustment for potential confounders, the hazard ratio (HR) for incident cancer per 10 beats/min increase in RHR was 1.00 (95% confidence interval [CI]: 0.93–1.07). There was a trend toward an increased risk of colorectal cancer in patients with higher RHR (HR 1.15, 95% CI 0.97–1.36). The risk of all-cause mortality was increased in patients in the highest quartile of RHR compared to the lowest quartile (HR 1.86, 95% CI 1.53–2.27), but no effect of RHR on cancer mortality was observed (HR 1.01, 95% CI 0.70–1.46).ConclusionsIn patients with manifest vascular disease, elevated RHR was related to a higher risk of premature all-cause mortality, but this was not due to increased cancer mortality. RHR was not related to risk of overall cancer incidence, although a relation between elevated RHR and incident colorectal cancer risk could not be ruled out.