Prognostic Roles of Neutrophil-to-Lymphocyte Ratio and Stromal Tumor-Infiltrating Lymphocytes and Their Relationship in Locally Advanced Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy

IntroductionThe neutrophil-to-lymphocyte ratio (NLR) and stromal tumor-infiltrating lymphocytes (sTILs) are associated with immunogenicity and prognosis of patients with triple-negative breast cancer (TNBC).ObjectiveTo investigated the prognostic roles of NLR and sTILs and their rela­tionship of TNBC patients treated with neoadjuvant chemotherapy (NAC).MethodsThe clinical data of 170 patients with locally advanced TNBC who received NAC from January 2010 to December 2014 were collected. The difference among variables was calculated by χ² test. The association between essential clinicopathological characteristics, pathological complete response (pCR), NLR, and sTILs with disease-free survival (DFS) was analyzed. Kaplan-Meier and Cox analysis were performed to address the effects of clinical parameters on prognosis.ResultsThere was a trend that TNBC patients with lower baseline NLR (NLR1) or higher sTILs scoring would obtain a better pCR rate. NLR1 and sTILs were not associated (p > 0.05). Patients with low NLR1 or high sTILs scoring had a significantly improved DFS compared to those with high NLR1 or low sTILs scoring (p = 0.002 and p = 0.001, respectively). The increased lymphocyte count in peripheral blood after NAC was associated with the improved DFS outcome in both high and low NLR1 groups. Cox analysis revealed that NLR1 and sTILs were independent prognostic predictors of DFS outcome (p < 0.001).ConclusionLow NLR1 and high sTILs were associated with better DFS outcome in locally advanced TNBC patients treated with NAC. Further studies are needed to explore the connection between systemic and local inflammatory/immune markers.     

Invasive Lobular Carcinoma Has Worse Outcome Compared with Invasive Ductal Carcinoma in Stage IV Breast Cancer with Bone-Only Metastasis

BackgroundInvasive lobular carcinoma (ILC) is more likely to have bone metastasis than invasive ductal carcinoma (IDC). However, the prognosis for bone metastasis in ILC and IDC is barely known. So, the aim of this study was to investigate the difference of prognosis between ILC and IDC accompanied by bone metastasis.MethodsWe evaluated the women with bone-only metastasis of defined IDC or ILC reported to the Surveillance, Epidemiology and End Results program from 2010 to 2016. Pearson''s χ² test was used to compare the differences of clinicopathologic factors between IDC and ILC. Univariate and multivariate analyses were performed to verify the effects of histological types (IDC and ILC) and other clinicopathologic factors on the overall survival (OS) and cancer-specific survival (CSS).ResultsOverall, 3,647 patients with IDC and 945 patients with ILC met the inclusion criteria and were analyzed in our study. The patients with ILC were more likely to be older and to have lower histological grade and a higher proportion of the HR*/HER2− subtype. However, less treatment was administered to ILC than IDC, such as surgery of the breast, radiation, and chemotherapy. Compared to patients with IDC, patients with ILC showed worse OS (median OS, 36 and 42 months, respectively, p < 0.001) and CSS (median CSS, 39 and 45 months, respectively, p < 0.001), especially in subgroups with HR*/HER2− subtype (OS, hazard ratio: 1.501, 95% CI 1.270–1.773, p < 0.001; CSS, hazard ratio: 1.529, 95% CI 1.281–1.825, p < 0.001), lower histological grade (I–II) (OS, hazard ratio: 1.411, 95% CI 1.184–1.683, p < 0.001; CSS, hazard ratio: 1.488, 95% CI 1.235–1.791, p < 0.001), or tumor burden, such as T_0–2 (OS, hazard ratio: 1.693, 95% CI 1.368–2.096, p < 0.001; CSS, hazard ratio: 1.76, 95% CI 1.405–2.205, p < 0.001) and N_1–2 (OS, hazard ratio: 1.451, 95% CI 1.171–1.799, p = 0.001; CSS, hazard ratio: 1.488, 95% CI 1.187–1.865, p = 0.001). Furthermore, older age, black race, unmarried status, higher tumor burden (T_3–4 and N₃), triple-negative subtype, and higher histological grade were independent risk factors for both OS and CSS. Surgery of the breast and chemotherapy could significantly improve the prognosis for patients.ConclusionPatients with ILC have worse outcomes compared to those with IDC when associated with bone-only metastasis, especially in subgroups with lower histological grade or tumor burden. More effective treatment measures may be needed for ILC, such as cyclin-dependent kinase 4/6 inhibitors, new targeted drugs, etc.     

Prognostic effect of preoperative serum albumin to globulin ratio in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

BackgroundAccurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.MethodsmRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 vs. high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel’s concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA).ResultsAmong 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16–58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26–1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27–1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23–1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24–1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 vs. C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16–1.99, P=0.002).ConclusionsIn our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.     

Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria: a meta-analysis of 18,421 patients

BackgroundOutcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria.MethodsTwo authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models.ResultsWe screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14–1.81; P<0.01] and DFS (HR =2.71; 95% CI: 2.23–3.28; P<0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30–3.79; P<0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24–3.07; P<0.01).ConclusionsMortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.     

Preoperative Platelet to Albumin Ratio Predicts Outcome of Patients with Non-Small-Cell Lung Cancer

Objective: The purpose of this study was to evaluate the predictive power of the platelet to albumin ratio (PAR) on survival outcomes of patients with non-small-cell lung cancer (NSCLC).Patients and Methods: In all, 198 patients with NSCLC were recruited. The X-tile software was performed to identify the optimal cutoff values for PAR, platelet to lymphocyte ratio (PLR), and neutrophil to lymphocyte ratio (NLR). The Kaplan–Meier method, univariate and multivariate analyses Cox regression were used to analyze the prognostic factors for overall survival (OS).Results: In all, 198 patients were enrolled, containing 146 (73.7%) men and 52 (26.3%) women. The optimal cutoff values for PAR, PLR, and NLR were 8.8×10⁹, 147.7, and 3.9, respectively. Patients with PAR > 8.8 × 10⁹ (P <0.001), PLR > 147.7 (P <0.001), and NLR >3.9 (P = 0.007) were associated with poor OS. Multivariate analyses found that PAR was an independent predictor in NSCLC patients (hazard ratio [HR]: 4.604, 95% confidence interval [CI]: 2.557–8.290, P <0.001).Conclusion: Preoperative PAR is a useful and potential prognostic biomarker in NSCLC patients who have received primary resection.     

A single-center,multidisciplinary experience with radium-223 dichloride in men with metastatic castrate-resistant prostate cancer

IntroductionWe aimed to investigate several clinical and biochemical parameters, including palliative external beam radiation therapy (EBRT) to predict survival in patients with metastatic castrate-resistant prostate cancer (mCRPC) treated with radium-223 (²²³Ra).MethodsWe tested known and possible prognostic parameters, including palliative EBRT, both prior and concurrent to ²²³Ra. Logrank test (Kaplan-Meier method) and Cox regression analysis were used to predict overall survival (OS).ResultsA total of 133 patients were treated with ²²³Ra; median age was 72 years. Median OS was 9.0 (95% confidence interval [CI] 7.4–10.6) months. By univariate analysis (log-rank test), baseline Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 (p=0.001), ≥5 cycles of ²²³Ra (p<0.001), baseline hemoglobin (Hb) ≥120 g/L (p <0.001), baseline total alkaline phosphatase (tALP) <110 U/L (p=0.001), and any prostate-specific antigen (PSA) decline at week 12 (p=0.013) were associated with increased OS. EBRT prior and/or concurrent to ²²³Ra showed a trend (p=0.051) towards inferior OS by univariate analysis only. By multivariate analysis, significant factors were PS 0–1 (hazard ratio [HR] 1.94, 95% CI 1.3–2.9, p=0.001), Hb ≥120 g/L (HR 0.5, 95% CI 0.3–0.9, p=0.011), and absence of docetaxel use prior to ²²³Ra (HR 1.86, 95% CI 1.08–3.22, p=0.026). With baseline Hb, tALP, and ECOG PS, we were able to divide patients into three groups with different median OS (months): 23.0 (95% CI 12.8–33.2), 8.0 (95% CI 6.7–9.3), and 5.0 (95% CI 3.1–6.9) for low-, intermediate-, and high-risk, respectively (p<0.001).ConclusionsWe found that ²²³Ra therapy can result in an OS of close to two years in carefully selected patients. Earlier administration of ²²³Ra therapy to fitter patients with mCRPC should be tested.     

Objective Response to First-Line Treatment as a Predictor of Overall Survival in Metastatic Breast Cancer: A Retrospective Analysis from Two Centers over a 25-Year Period

IntroductionThe purpose of this study was to study the efficacy of subsequent treatment lines for metastatic breast cancer (MBC), as well as the association between radiologic objective response rate (ORR) and overall survival (OS).MethodsIn this retrospective study, consecutive patients treated for MBC in two centers in Greece from January 1, 1992, to December 31, 2016, were identified and clinicopathologic data regarding tumor characteristics and administered treatments were collected. The efficacy per treatment line in terms of ORR, progression-free survival (PFS) and OS, as well as the prognostic value of ORR at first line were investigated.ResultsA total of 977 patients with MBC were identified; 950 received any treatment. At first line, ORR was 43.5%, PFS 11.4 months (95% CI 10.4–12.4), and median OS 52.4 months (95% CI 47.7–57.1). Lower ORR and shorter PFS were observed with each subsequent line. Median OS was significantly longer for patients that had an objective response at first line, 61.9 months (95% CI 51.1–69.7) for responders versus 41.3 months (95% CI 44.1–63.3) for nonresponders (p < 0.001). In multivariable analysis, failure to achieve an objective response was an independent predictor of poor survival (hazard ratio 1.70, 95% CI 1.34–2.15, p < 0.001).ConclusionLate treatment lines for MBC seem to have limited efficacy, while response to first-line therapy is associated with long-term survival. The latter should be considered in the treatment strategy of patients with MBC.     

Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV-positive patients

Introduction

Although antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation.

Methods

Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm³ or prior AIDS diagnosis). Predictors for late ART initiation and mortality were determined.

Results

A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46–241) cells/mm³. Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm³ in 2008 to a peak of 302 cells/mm³ after 2011 (p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001). Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27–0.59; p<0.001), sex (male vs. female; OR 1.51, 95% CI 1.18–1.93; p=0.001) and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24–2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77–5.21; p<0.001). Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19–3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31–3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18–7.04; p<0.001) and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.−4.36; p=0.035).

Conclusions

Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented.     

Monocyte-to-lymphocyte ratio: a potential novel predictor for acute kidney injury in the intensive care unit

Monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) are considered as surrogate inflammatory indexes. Previous studies indicated that NLR was associated with the development of septic acute kidney injury (AKI). The objective of the present study was to explore the value of MLR and NLR in the occurrence of AKI in intensive care unit (ICU) patients. The clinical details of adult patients (n = 1500) who were admitted to the ICU from January 2016 to December 2019 were retrospectively examined. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes criteria. The development of AKI was the main outcome, and the secondary outcome was in-hospital mortality. Overall, 615 (41%) patients were diagnosed with AKI. Both MLR and NLR were positively correlated with AKI incidence (p < 0.001). Multivariate logistic regression analysis suggested that the risk value of MLR for the occurrence of AKI was nearly three-fold higher than NLR (OR = 3.904, 95% CI: 1.623‒9.391 vs. OR = 1.161, 95% CI: 1.135‒1.187, p < 0.001). The areas under the receiver operating characteristic curve (AUC) for MLR and NLR in the prediction of AKI incidence were 0.899 (95% CI: 0.881‒0.917) and 0.780 (95% CI: 0.755‒0.804) (all p < 0.001), with cutoff values of 0.693 and 12.4. However, the AUC of MLR and NLR in the prediction of in-hospital mortality was 0.583 (95% CI: 0.546‒0.620, p < 0.001) and 0.564 (95% CI: 0.528‒0.601, p = 0.001). MLR, an inexpensive and widely available parameter, is a reliable biomarker in predicting the occurrence of AKI in ICU patients.     

Development and validation of a nomogram for predicting acute kidney injury after orthotopic liver transplantation

BackgroundWe aim to develop and validate a nomogram model for predicting severe acute kidney injury (AKI) after orthotopic liver transplantation (OLT).MethodsA total of 576 patients who received OLT in our center were enrolled. They were assigned to the development and validation cohort according to the time of inclusion. Univariable and multivariable logistic regression using the forward variable selection routine were applied to find risk factors for post-OLT severe AKI. Based on the results of multivariable analysis, a nomogram was developed and validated. Patients were followed up to assess the long-term mortality and development of chronic kidney disease (CKD).ResultsOverall, 35.9% of patients were diagnosed with severe AKI. Multivariable logistic regression analysis revealed that recipients’ BMI (OR 1.10, 95% CI 1.04–1.17, p = 0.012), hypertension (OR 2.32, 95% CI 1.22–4.45, p = 0.010), preoperative serum creatine (sCr) (OR 0.96, 95% CI 0.95–0.97, p < 0.001), and intraoperative fresh frozen plasm (FFP) transfusion (OR for each 1000 ml increase 1.34, 95% CI 1.03–1.75, p = 0.031) were independent risk factors for post-OLT severe AKI. They were all incorporated into the nomogram. The area under the ROC curve (AUC) was 0.73 (p < 0.05) and 0.81 (p < 0.05) in the development and validation cohort. The calibration curve demonstrated the predicted probabilities of severe AKI agreed with the observed probabilities (p > 0.05). Kaplan-Meier survival analysis showed that patients in the high-risk group stratified by the nomogram suffered significantly poorer long-term survival than the low-risk group (HR 1.92, p < 0.01). The cumulative risk of CKD was higher in the severe AKI group than no severe AKI group after competitive risk analysis (HR 1.48, p < 0.05).ConclusionsWith excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for severe AKI and poor long-term prognosis after OLT.     

Pathological response and survival after neoadjuvant therapy for breast cancer: A 30-year study

Purpose of the researchHER2-positive and triple-negative breast cancer (TNBC) still have a poor prognosis. Pathological complete response (pCR) is usually considered a surrogate marker for outcome. The aim of this study was to reconsider these parameters on a large population after a long follow-up. 348 patients with unilateral breast cancer who received neoadjuvant treatment at our institution over 30 years were included.ResultsPatients were classified according to hormonal receptors (HR) and HER2. Median follow-up was 7 years. pCR was significantly lower in HR+/HER2? tumors (P < 0.0001). The 7-year OS rates were 76.1% (HR+/HER2?), 60.1% (TNBC), 72.4% (HR+/HER2+), and 49.9% (HR?/HER2+). Disease-free survival (DFS) and OS differed significantly according to pCR. Among HER2+ patients, pCR rate, DFS and OS were greater with trastuzumab.ConclusionsTNBC and HR?/HER2+ tumors have the worst outcome. pCR remains a significant prognostic factor. Trastuzumab strongly improves pCR and survival in HER2+ tumors.     

CAGS AND ACS EVIDENCE BASED REVIEWS IN SURGERY. 47: Does the long-term use of aspirin decrease the risk of death due to cancer?

Question: Does the long-term use of acetylsalicylic acid (ASA) decrease the risk of death due to cancer? Design: Pooled analysis. Data source: Cochrane Collaboration, Database of Systematic reviews, PubMed and Embase. Study selection: Individual patient data from all randomized trials of daily ASA versus no ASA with a mean duration of scheduled trial treatment of 4 years or longer were used to determine the effect of allocation to ASA on risk of cancer death in relation to scheduled duration of trial treatment for gastrointestinal (GI) and non-GI cancers. Results: In 8 eligible trials (25 570 patients, 674 cancer-related deaths), allocation to ASA reduced the risk of death due to cancer (pooled odds ratio [OR] 0.79, 95% confidence interval [CI] 0.68–0.92, p = 0.003). On analysis of individual patient data, which were available from 7 trials (23 535 patients, 657 cancer-related deaths), the benefit was apparent only after 5 years’ follow-up (all cancers, hazard ratio [HR] 0.66, 95% CI 0.50–0.87; GI cancers, 0.46, 95% CI 0.27–0.77; both p = 0.003). The 20-year risk of cancer death (deaths in 12 659 patients in 3 trials) remained lower in the ASA groups than in the control groups (all solid organ cancers, HR 0.80, 95% CI 0.72–0.88, p < 0.001; GI cancers, HR 0.65, 95% CI 0.54–0.78, p < 0.001), and benefit increased (interaction p = 0.01) with scheduled duration of trial treatment (≥ 7.5 years: all solid cancers, HR 0.69, 95% CI 0.54–0.88, p = 0.003; GI cancers, HR 0.41, 95% CI 0.26–0.66, p < 0.001). The latent period before an effect on deaths could be observed was about 5 years for esophageal, pancreatic, brain and lung cancer, but was longer for stomach, colorectal and prostate cancer. For lung or esophageal cancer, the benefit was confined to adenocarcinomas, and the overall effect on 20-year risk of cancer-related death was greatest for adneocarcinomas (HR 0.66, 95% CI 0.56–0.77, p < 0.001). The benefit was unrelated to ASA dose (75 mg or higher), sex or smoking, but was increased with age; the absolute reduction in 20-year risk of cancer-related death reached 7.08% at age 65 years and older. Conclusion: Daily ASA reduced deaths due to several common cancers during and after the trials. The benefit increased with duration of treatment and was consistent across the different study populations. These findings have implications for guidelines on use of ASA and for understanding carcinogenesis and its susceptibility to drug intervention.     

ALP bouncing and LDH normalization in bone metastatic castration-resistant prostate cancer patients under therapy with Enzalutamide: an exploratory analysis

BackgroundIn bone metastatic castration-resistant prostate cancer (bmCRPC) treated with Enzalutamide commonly used prostate-specific antigen (PSA) can be misleading since initial PSA-flares may occur. In other therapies, bouncing of alkaline phosphatase (ALP-bouncing) was shown to be a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) is usually associated with better outcome. We evaluated the prognostic ability of ALP-bouncing, LDH, PSA, and the combination of these markers after initiation of Enzalutamide.MethodsEighty-nine patients with bmCRPC and dynamic changes of PSA, LDH and ALP were analyzed. ALP-bouncing, an increase after therapy start followed by a decline below baseline during the first 8 weeks, LDH-normalization and PSA-decline were analyzed regarding their association with survival using Kaplan-Meier analyses and uni- and multivariate (UV and MV) Cox-regression models.ResultsIn Kaplan-Meier analysis a PSA-decline >50%, LDH-normalization and ALP-bouncing were associated with longer median progression-free survival (PFS) with 7 [95% confidence interval (CI): 4.2–9.8] vs. 3 (2.3–3.7) months for PSA-decline (log-rank P<0.01), 6 (4.1–8) vs. 2 (1.2–2.8) for LDH-normalization (P<0.01) and 8 (0–16.3) vs. 3 (1.9–4.1) for ALP-bouncing (P=0.01). Analysis of overall survival (OS) showed similar, not for all parameters significant, results with 17 (11.7–22.3) vs. 12 (7.0–17.1) months for PSA (P=0.35), 17 (13.2–20.8) vs. 7 (5.8–8.2) for LDH-normalization (P<0.01) and 19 (7.9–30.1) vs. 12 (7.7–16.3) for ALP-bouncing (P=0.32). In UV analysis, ALP-bouncing [hazard ratio (HR): 0.5 (0.3–1.0); P=0.02], PSA-decline >50% [HR: 0.5 (0.3–0.7); P<0.01] and LDH-normalization [HR: 0.4 (0.2–0.6); P<0.01] were significantly associated with longer PFS. For OS, LDH-normalization significantly prognosticated longer survival [HR: 0.4 (0.2–0.6); P<0.01]. In MV analysis, LDH-normalization was associated with a trend towards better OS [HR: 0.5 (0.2–1.1); P=0.09]. Comparing ALP-bouncing, LDH-normalization and PSA-decline with a PSA-decline alone, Kaplan-Meier analysis showed significantly longer PFS [11 (0.2–21.8) vs. 4 (0–8.6); P=0.01] and OS [20 (17.7–22.3) vs. 8 (0.3–15.7); P=0.02] in favor of the group presenting with the beneficial dynamics of all three markers. In UV analysis, the presence of favorable changes in the three markers was significantly associated with longer PFS [HR: 0.2 (0.1–0.7); P<0.01] and OS [HR: 0.3 (0.1–0.8); P=0.02].ConclusionsALP-bouncing and LDH-normalization may add to identification of bmCRPC-patients with favorable prognosis under Enzalutamide.     

Use of the systemic inflammation response index (SIRI) as a novel prognostic marker for patients on peritoneal dialysis

BackgroundThe systemic inflammatory response index (SIRI), a novel inflammation maker, has proven to be associated with prognostic outcomes in various diseases. However, few studies have been conducted assessing how SIRI may influence outcomes of patients on peritoneal dialysis (PD). Herein, we assessed the predictive value of SIRI on mortality all-cause mortality, including cardiovascular disease (CVD) in PD patients.MethodsA total of 646 PD patients were enrolled in this study. PD patients received regular PD treatments at the Zhujiang Hospital from 1 January 2011 to 31 December 2018. SIRI values could be computed as follows: neutrophil count × monocyte count/lymphocyte count. Patients were divided into two groups according to the median level of SIRI. Cox regression analysis and Kaplan–Meier methods were applied to analyze the relationship between SIRI and mortality outcomes in PD patients.ResultsDuring the median 31-month follow-up period, 97 (15.0%) PD patients died from all-causes, and 47 (49.0%) died of CVD. Kaplan–Meier analyses revealed that a high SIRI corresponded to the high mortality of all-cause deaths, including CVD (both p < 0.001) in patients on PD. After adjusting for potential confounders, the higher SIRI level was significantly associated with an increased all-cause mortality (HR: 2.007, 95% CI: 1.304–3.088, p = 0.002) and cardiovascular mortality (HR: 2.847, 95% CI: 1.445–5.608, p = 0.002).ConclusionsSIRI was a promising predictor of mortality in PD patients, with a higher SIRI corresponding to increased risk of mortality.     

Outcomes of critically ill patients with acute kidney injury in COVID-19 infection: an observational study

BackgroundEarly reports indicate that AKI is common during COVID-19 infection. Different mortality rates of AKI due to SARS-CoV-2 have been reported, based on the degree of organic dysfunction and varying from public to private hospitals. However, there is a lack of data about AKI among critically ill patients with COVID-19.MethodsWe conducted a multicenter cohort study of 424 critically ill adults with severe acute respiratory syndrome (SARS) and AKI, both associated with SARS-CoV-2, admitted to six public ICUs in Brazil. We used multivariable logistic regression to identify risk factors for AKI severity and in-hospital mortality.ResultsThe average age was 66.42 ± 13.79 years, 90.3% were on mechanical ventilation (MV), 76.6% were at KDIGO stage 3, and 79% underwent hemodialysis. The overall mortality was 90.1%. We found a higher frequency of dialysis (82.7% versus 45.2%), MV (95% versus 47.6%), vasopressors (81.2% versus 35.7%) (p < 0.001) and severe AKI (79.3% versus 52.4%; p = 0.002) in nonsurvivors. MV, vasopressors, dialysis, sepsis-associated AKI, and death (p < 0.001) were more frequent in KDIGO 3. Logistic regression for death demonstrated an association with MV (OR = 8.44; CI 3.43–20.74) and vasopressors (OR = 2.93; CI 1.28–6.71; p < 0.001). Severe AKI and dialysis need were not independent risk factors for death. MV (OR = 2.60; CI 1.23–5.45) and vasopressors (OR = 1.95; CI 1.12–3.99) were also independent risk factors for KDIGO 3 (p < 0.001).ConclusionCritically ill patients with SARS and AKI due to COVID-19 had high mortality in this cohort. Mortality was largely determined by the need for mechanical ventilation and vasopressors rather than AKI severity.     

Prognostic significance of serum lactate dehydrogenase in patients undergoing radical cystectomy for bladder cancer

BackgroundTo investigate the prognostic significance of preoperative serum lactate dehydrogenase (LDH) in patients undergoing radical cystectomy for bladder cancer (BCa).Patients and methodsA cohort of 263 patients undergoing open or laparoscopic radical cystectomy between 2011 and 2016 was studied. Baseline characteristics, hematological variables, follow-up data were collected. Kaplan-Meier curves and Cox proportional hazard regression model were applied to assess the relationship between LDH and overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS).ResultsAfter a median 34.2 (22.9–45.8) months follow-up, all-cause death, cancer-specific death, and disease recurrence occurred in 66 patients, 50 patients, and 91 patients. The elevation of serum LDH was associated with several unfavorable parameters, including advanced age, continent cutaneous urinary diversion, increased neutrophil-to-lymphocyte ratio, decreased lymphocyte-to-monocyte ratio. Patients with a higher serum LDH (> 220 U/L) had a worse OS (P < 0.001), CSS (P < 0.001) and DFS (P < 0.001). Multivariate Cox analysis suggested that elevated LDH was an independent predictor for OS (hazard ratio [HR]: 3.113, 95% confidence interval [CI]: 1.524–6.358; P = 0.002), CSS (HR: 4.564, 95% CI: 2.008–10.373; P < 0.001), DFS (HR: 2.051, 95% CI: 1.125–3.739; P = 0.019). Medical history of diabetes, high pT stage, and positive lymph node also were adverse predictors for oncological outcomes of BCa patients in multivariate analysis.ConclusionsPreoperative serum LDH is an independent prognostic biomarker for OS, CSS, and DFS in patients undergoing radical cystectomy for BCa, which can be incorporated into prognostic models.     

Impact of parathyroidectomy among nondiabetic hemodialysis patients with severe hyperparathyroidism

BackgroundParathyroidectomy (PTX) is a treatment for hyperparathyroidism (HPT) and has uncertain risks and benefits. The aim of this study was to evaluate the effect of PTX versus nonoperative treatment among nondiabetic hemodialysis patients.MethodsA retrospective matched cohort study was performed. Each PTX patient was matched with one patient who had severe HPT but rejected PTX. The patients were matched by sex, birth date, date of first dialysis, nondiabetic status, and left ventricular ejection fraction. The serum markers, survival, main adverse cardiovascular and cerebrovascular event (MACCE) rates, and hospitalization were compared between the PTX patients and matched non-PTX patients.ResultsThere were 1143 patients at our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2020. Of these, 75 PTX patients were matched with 75 non-PTX patients. Rapid decreases in the mean intact parathyroid hormone, calcium and phosphorus concentrations, and a gradual increase in hemoglobin concentration were observed in the PTX group. The mortality was 2.9 per 100 patient-years in the PTX group and 10.9 per 100 patient-years in the non-PTX group (p < 0.001). Compared with non-PTX patients, PTX patients had an adjusted HR for death of 0.236 (95% CI 0.108–0.518). The cumulative MACCE rates were 6.7 per 100 patient-years in the PTX group and 15.2 per 100 patient-years in the non-PTX group (p < 0.001). The adjusted HR of the occurrence of first MACCE for PTX patients compared with non-PTX patients was 0.524 (95% CI 0.279-0.982). The cumulative hospitalization rates were 50.3 per 100 patient-years in the PTX group and 66.5 per 100 patient-years in the matched non-PTX group (p < 0.001).ConclusionsCompared with non-PTX patients, PTX was associated with an improvement in the biochemical measures and patient-level outcomes in nondiabetic hemodialysis patients with severe HPT.     

Anatomic versus non-anatomic resection of hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis

The efficacy of anatomical resection (AR) and non-anatomical resection (NR) in the treatment of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remains unknown. This study compared the safety and outcomes of these surgical procedures. A systematic literature search was conducted. The main outcomes were overall survival (OS), disease-free survival (DFS). Overall hazard ratio (HR) was calculated from Kaplan–Meier plots and outcomes using random-effects models. There was no significant difference in postoperative complications between the AR and NR groups (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.72–1.17, p = 0.496). OS was higher with AR at 1 year (RR: 0.66, 95% CI: 0.45–0.98, p = 0.037), 3 years (RR: 0.64, 95% CI: 0.50–0.82, p = 0.000), and 5 years (RR: 0.76, 95% CI: 0.65–0.89, p = 0.001). AR was associated with a higher OS rate (HR: 0.62, 95% CI: 0.47–0.82, p = 0.001). AR was associated with improved DFS at 1 year (RR: 0.65, 95% CI: 0.52 to 0.82, p = 0.000), 3 years (RR: 0.75, 95% CI: 0.66 to 0.86, p = 0.000), and 5 years (95% CI: 0.75 to 0.94, p = 0.002). Compared with NR, AR had significant advantages on overall HR of DFS (HR: 0.64, 95% CI: 0.45 to 0.91, p = 0.012). In conclusion, AR was associated with higher rates of OS and DFS in HCC patients with MVI. Thus, for well-presented liver function HCC patients which are predicted to have positive MVI, AR is recommended.     

Peritoneal transport status and first episode of peritonitis: a large cohort study

BackgroundPeritonitis is one of the most serious complications of peritoneal dialysis (PD). This study aimed to explore the relationship between peritoneal transport status and the first episode of peritonitis, as well as the prognosis of patients undergoing continuous ambulatory peritoneal dialysis (CAPD).MethodA retrospective cohort study was conducted, analyzing data of CAPD patients from 1st January 2009, to 31st December 2017. Baseline data within 3 months after PD catheter placement was recorded. Cox multivariate regression analysis was performed to determine the risk factors for the first episode of peritonitis, technique failure and overall mortality.ResultsA total of 591 patients were included in our analysis, with a mean follow-up visit of 49 months (range: 27–75months). There were 174 (29.4%) patients who had experienced at least one episode of peritonitis. Multivariate Cox regression analysis revealed that a higher peritoneal transport status (high and high-average) (HR 1.872, 95%CI 1.349–2.599, p = 0.006) and hypoalbuminemia (HR 0.932,95% CI 0.896, 0.969, p = 0.004) were independent risk factors for the occurrence of the first episode of peritonitis. In addition, factors including gender (male) (HR 1.409, 95%CI 1.103, 1.800, p = 0.010), low serum albumin (HR 0.965, 95%CI 0.938, 0.993, p = 0.015) and the place of residence (rural) (HR 1.324, 95%CI 1.037, 1.691, p = 0.024) were independent predictors of technique failure. Furthermore, low serum albumin levels (HR 0.938, 95%CI 0.895, 0.984, p = 0.008) and age (>65years) (HR 1.059, 95%CI 1.042, 1.076, p < 0.001) were significantly associated with the risk of overall mortality of PD patients.ConclusionsBaseline hypoalbuminemia and a higher peritoneal transport status are risk factors for the first episode of peritonitis. Factors including male gender, hypoalbuminemia, and residing in rural areas are associated with technique failure, while hypoalbuminemia and age (>65years) are predictors of the overall mortality in PD patients. Nevertheless, the peritoneal transport status does not predict technique failure or overall mortality of PD patients.