The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Mesenchymal stem cells ameliorate cisplatin-induced acute kidney injury via let-7b-5p.

Acute kidney injury (AKI) is a clinically common kidney disease. Age is an important factor that contributes to the susceptibility to AKI. Mesenchymal stem cells (MSCs) are a promising therapy for AKI, and miRNAs in exosomes (Exos) derived from MSCs are an important aspect of MSC treatment. However, the therapeutic effect of miRNA from MSC-derived Exos on AKI and the related mechanism have not been fully clarified. Whether there is a relationship between the mechanisms of senescence for AKI susceptibility and the therapeutic effect of MSCs has not been studied. We compared the degree of cisplatin-induced AKI injury in young and elderly mice and investigated changes in the expression of p53 and markers of DNA damage and apoptosis, which are important in both senescence and AKI. Ageing mice exhibited increased expression of p53 and pro-apoptosis markers. Upregulation of the senescence-associated DNA damage/p53 pathway may be an important susceptibility factor for cisplatin-induced AKI. Treatment with MSCs can reduce the degree of DNA damage and suppress p53 expression and apoptosis. Upon screening for differentially expressed miRNAs, let-7b-5p levels were found to be lower in aged mice than in young mice, and MSC treatment increased let-7b-5p levels. The presence of let-7b-5p in MSC-derived Exos alleviates tubular epithelial cell apoptosis by inhibiting p53, which reduces DNA damage and apoptosis pathway activity. Let-7b-5p downregulation may lead to increased renal AKI susceptibility, thus indicating that this miRNA is a potential driver of the MSC treatment response in AKI.

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).

Metal-Free Photosynthesis of Alkylated Benzimidazo[2,1-a]isoquinoline-6(5H)-ones and Indolo[2,1-a]isoquinolin-6(5H)-ones in PEG-200.

A visible-light-induced decarboxylation reaction was developed for the synthesis of alkylated benzimidazo[2,1-a]isoquinoline-6(5H)-ones and indolo[2,1-a]isoquinolin-6(5H)-ones under metal-free conditions. Impressively, metal catalysts and traditionally volatile organic solvents could be effectively avoided.

Therapeutic effect of intravenous sodium thiosulfate for uremic pruritus in hemodialysis patients.

OBJECTIVES: This study aimed to compare the efficacy of intravenous sodium thiosulfate (IV STS) with that of loratadine in the treatment of uremic pruritus in hemodialysis (HD) patients. METHODS: This retrospective study included 44 HD patients with pruritus aged over 18 years between June 2018 and January 2020 at the Aerospace Center Hospital of China. Twenty-four HD patients received 3.2 g IV STS treatment three times per week at the end of each HD session for 8 weeks. Twenty HD patients received loratadine (10 mg/day) for 8 weeks. Pruritus intensity was measured using a visual analog scale (VAS) and the detailed pruritus score (DPS) at three time points. The safety of STS was evaluated according to adverse event symptoms and biological variable changes. RESULTS: There was no significant difference between the STS and loratadine groups in age, sex, characteristics of pruritus, or other clinical variables before treatment. After 8 weeks of treatment, the VAS score (7.07 ± 2.56 and 2.67 ± 2.01) and DPS (30.72 ± 4.81 and 8.04 ± 2.86) decreased significantly in the STS group (p < 0.05). The mean decrease in VAS score (6.89 ± 1.98 and 6.34 ± 2.35) and DPS (28.90 ± 3.24 and 26.92 ± 2.41) in the loratadine group was not statistically significant (p > 0.05). There were no morbidities or mortalities associated with the use of either drug. All biological variables remained stable after therapy. CONCLUSIONS: STS can improve uremic pruritus in HD patients. However, literature on the subject remains lacking. Close monitoring for adverse effects is advised.

Prognostic value of neutrophil-to-lymphocyte ratio in advanced nasopharyngeal carcinoma: a large institution-based cohort study from an endemic area.

BACKGROUND: Findings remain unclear whether neutrophil-to-lymphocyte ratio (NLR) detrimentally affects advanced nasopharyngeal carcinoma (NPC) prognosis. We aim to evaluate the prognostic value of NLR in patients with NPC based on a large-scale cohort from an endemic area. METHODS: We selected patients retrospectively from a cohort examining long-term cancer outcomes following diagnosis. Neutrophil counts and lymphocyte counts were assessed prior to treatment. Kaplan-Meier method and log-rank test were used to calculate and compare survival outcomes. Additionally, Cox proportional hazards model was utilized to carry out univariate and multivariate analyses. RESULTS: Between October 2009 and August 2012, we enrolled 1550 consecutive NPC patients staged II-IVB. The median value of NLR was 2.27 (interquartile range [IQR], 1.71-3.12). Determined by operating characteristic curve using overall survival (OS) as an endpoint, the cutoff value for NLR was 2.50. At 5 years, NLR > 2.50 was associated with inferior OS (90.3% vs 82.5%; P < 0.001), distant metastasis-free survival (DMFS, 89.4% vs 85.0%; P = 0.014), and progression-free survival (PFS, 80.9% vs 76.5%; P = 0.031) than NLR ≤2.50. In multivariate analysis, NLR was found to be a significant prognostic factor for OS (HR, 1.72; 95% CI, 131-2.24; P < 0.001), DMFS (HR, 1.45; 95% CI, 1.10-1.92; P = 0.009), and PFS (HR, 1.29; 95% CI, 1.04-1.59; P = 0.021). CONCLUSION: Pretreatment NLR independently affects survival. Our findings suggest that NLR measurements will be of great clinical significance in the management of NPC.

Prognostic Value of Circulating Lipoprotein in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

BACKGROUND/AIMS: Lipoproteins have been reported to be associated with prognosis in various cancers; however, the prognostic value of lipoproteins in patients with nasopharyngeal carcinoma (NPC) remains largely unknown. We aim to asses the role of circulating lipoproteins in locoregionally advanced NPC patients. METHODS: Between October 2009 and August 2012, a total of 1,081 patients with stage III-IVB NPC were included in the analysis. Circulating high-density lipoprotein (HDL) and low-density lipoprotein (LDL) are the two key lipoproteins, which were measured at baseline. Receiver operating characteristic (ROC) curve analysis was used to evaluate different cut-off points for lipoproteins. Actuarial rates were performed using Kaplan-Meier methods and the log-rank test. RESULTS: The cutoff points of HDL, LDL, and LDL/HDL ratio were 1.17 mmol/L, 3.75 mmol/L, and 2.73, respectively. At 5 years, high HDL (> 1.17 mmol/L) was significantly associated with better overall survival (OS, 86.6% vs. 78.9%; P=0.004), distant metastasis-free survival (DMFS, 86.9% vs. 80.8%; P=0.004), locoregional relapse-free survival (LRFS, 90.8% vs. 85.4%; P=0.010), and progression-free survival (PFS, 79.1% vs. 70.2%; P= 0.001) than low HDL (≤1.17 mmol/L). In contrast, high LDL (> 3.75 mmol/L) tend to be inferior OS (79.1% vs. 84.9%; P= 0.016) in compassion with low LDL (≤3.75 mmol/L). Likewise, patients with high LDL/HDL ratio (> 2.73) tend to be inferior OS (79.3% vs. 86.9%; P=0.001), DMFS (81.9% vs. 86.5%; P=0.030), and PFS (72.6% vs. 77.8%; P= 0.034) than those of low LDL/HDL ratio (≤2.73). In multivariate analysis, baseline HDL was found to be a significant prognostic factor for LRFS (HR= 0.65; 95% CI, 0.45-0.93; P= 0.019) and PFS (HR=0.75; 95% CI, 0.58-0.98; P= 0.034). CONCLUSIONS: Circulating HDL is significantly associated with treatment outcomes in patients with locoregionally advanced NPC. We suggest that HDL measurements will be of great clinical significance in the management of NPC.

The detrimental effects of radiotherapy interruption on local control after concurrent chemoradiotherapy for advanced T-stage nasopharyngeal carcinoma: an observational, prospective analysis.

BACKGROUND: Previous studies have reported radiotherapy interruption (RTI) is associated with poor local control in two-dimensional radiotherapy (2DRT) era. However, it remains unclear whether RTI still affects local control for advanced T stage (T3-4) in the intensity-modulated radiation therapy (IMRT) era. We aim to evaluate whether RTI affects local control for T3-4 NPC treated with definitive IMRT. METHODS: In this observational prospective study, 447 T3-4 NPC patients treated with IMRT plus concurrent chemotherapy were included. All patients completed the planned radiotherapy course, and RTI was defined as the actual time taken to finish the prescribed course of radiotherapy minus the planned radiotherapy time. Receiver operating characteristic (ROC) curve was used for determined the cutoff point of RTI. The effects of RTI on local control were analyzed in multivariate analysis. RESULTS: At 5 years, the local relapse-free survival (LRFS) and overall survival (OS) rates were 93.7 and 85.7%, respectively. The cutoff RTI for LRFS was 5.5 days by ROC curve. Compared to patients with RTI >  5 days, patients with RTI ≤ 5 days had a significantly lower rate of LRFS (97% vs. 83%; P < 0.001). In multivariate analysis, RTI was a risk factor independently associated with LRFS (HR = 9.64, 95% CI, 4.10-22.65), but not for OS (HR = 1.09, 95% CI, 0.84-1.64). CONCLUSIONS: The current analysis demonstrates a significant correlation between prolonged RTI and local control in NPC, even when concurrent chemotherapy is used. We consider that attention to RTI seems to be warranted for patients with advanced T-stage NPC in the era of IMRT.

Energy restriction in renal protection.

Energy restriction (ER) has been widely studied as a novel intervention, and its ability to prolong life has been fully demonstrated. For example, ER can significantly extend the lifespans of model flies, worms, rodents and other mammals. The role of ER in renal protection has also been elucidated. In preclinical studies, adjusting total energy intake or consumption of specific nutrients has prophylactic or therapeutic effects on ageing-related kidney disease and acute and chronic kidney injury. Amino acid restriction has gradually attracted attention. ER mimetics have also been studied in depth. The protective mechanisms of ER and ER mimetics for renal injury include increasing AMP-activated protein kinase and sirtuin type 1 (Sirt1) levels and autophagy and reducing mammalian target of rapamycin, inflammation and oxidative stress. However, the renal protective effect of ER has mostly been investigated in rodent models, and the role of ER in patients cannot be determined due to the lack of large randomised controlled trials. To protect the kidney, the mechanism of ER must be thoroughly researched, and more accurate diet or drug interventions need to be identified.

Pentraxin-3 in Thrombolytic Therapy for Acute Ischemic Stroke: No Relation with Curative Effect and Prognosis.

BACKGROUND Pentraxin-3 (PTX3) is considered a high quality inflammatory marker of the severity and prognosis of several diseases, however, the value of PTX3 in thrombolytic therapy for acute ischemic stroke remains unclear and PTX3 is still controversial in evaluating the prognosis of stroke patients. In this study, we investigated the association of PTX3 with thrombolytic therapy in patients with acute ischemic stroke. MATERIAL AND METHODS Forty-seven stroke patients who received thrombolytic therapy within 4.5 hours after symptom onset were enrolled consecutively between July 2016 and June 2017. All the patients underwent multiphase CTA (computerized tomography angiography) or CT perfusion before thrombolysis with no indication for endovascular treatment. Initial and 24 hours of National Institute of Health Stroke Scale (NIHSS) scores and serum PTX3 level, stroke risk factors and predictors, and mRS (modified Rankin scale) at 3 months were collected prospectively. Predictors of thrombolytic therapy effect and long-term prognosis were investigated by univariate and multivariate logistic regression. RESULTS The 24 hour NIHSS score and the treatment time was associated with symptom improvement, while the PTX3 level had no association with neurological improvement and prognosis in stroke patients receiving thrombolytic therapy. CONCLUSIONS PTX3 is not suitable to serve as an indicator of thrombolytic efficacy and had no association with long-term prognosis in stroke patients receiving thrombolytic therapy.

Characteristics of and risk factors for death in elderly patients with acute kidney injury: a multicentre retrospective study in China.

PURPOSE OF THE STUDY: The incidence of acute kidney injury (AKI) with a poor prognosis in the elderly has been increasing each year. This study aimed to investigate the clinical characteristics of and risk factors for death from AKI in the elderly and help improve prognosis. STUDY DESIGN: This study was a retrospective cohort study based on data from adult patients (≥18 years old) admitted to 15 hospitals in China between 1 January 2009 and 31 December 2011. The characteristics of AKI in the elderly were compared with those in younger patients. RESULTS: In elderly patients with AKI, rates of hypertension, cardiovascular disease and multiple organ dysfunction syndrome (MODS) were higher than in younger patients (44.2% vs 31.2%, 16.1% vs 4.6% and 20.9% vs 16.9%, respectively), the length of ICU stay was longer (3.8 days vs 2.7 days, P=0.019) and renal biopsy (1.0% vs 7.13%, P<0.001) and dialysis (9.6% vs 19.2%, P<0.001) were performed less. Hospital-acquired (HA) AKI was more common than community-acquired (CA) AKI (60.3% vs 39.7%), while the most common cause of AKI was pre-renal (53.5%). Multiple logistic regression analysis showed that age (OR 1.041, 95% CI 1.023 to 1.059), cardiovascular disease (OR 1.980, 95% CI 1.402 to 2.797), cancer (OR 2.302, 95% CI 1.654 to 3.203), MODS (OR 3.023, 95% CI 1.627 to 5.620) and mechanical ventilation (OR 2.408, 95% CI 1.187 to 4.887) were significant risk factors for death. CONCLUSIONS: HA-AKI and pre-renal AKI were more common in the elderly. Age, cardiovascular disease, cancer, MODS and mechanical ventilation were independent risk factors for death in the elderly with AKI.

Clinical Study of Intracranial and Extracranial Atherosclerotic Stenosis in Spontaneous Intracerebral Hemorrhage Patients.

BACKGROUND AND PURPOSE: Nowadays, researchers had begun to focus on the use of antiplatelet and statins in patients with spontaneous intracerebral hemorrhage (sICH), but atherosclerosis treatment remains uncertain in these patients. We aimed to investigate the incidence and characteristics of intracranial and extracranial atherosclerotic stenosis in these patients and analyze its related risk factors. METHODS: Intracranial and extracranial arteries of consecutive patients with sICH were studied retrospectively with computed tomography angiography of head and neck. The risk factors, severity, and distribution of atherosclerotic stenosis were examined and analyzed. RESULTS: We included 226 patients with sICH, of whom 110 patients (48.7%) had atherosclerotic stenosis. Of the patients, 57 (51.8%) had intracranial stenosis and 75 (68.2%) had multiple stenosis. A total of 1870 vessels were examined and 287 vessels (15.3%) had atherosclerotic stenosis, of which 217 cases (75.6%) were mild stenosis. Intracranial and extracranial atherosclerosis was more likely to be found in patients with advanced age (P < .001), diabetes mellitus (P = .008), non-deep hemorrhage (P = .011). CONCLUSIONS: Atherosclerotic stenosis is common in patients with sICH, and is characterized by mild stenosis and the involvement of multiple sites. The stenosis of the vertebrobasilar system is relatively severe. Advanced age, diabetes mellitus, and non-deep bleeding are its related risks.

Prognostic value of serum Epstein-Barr virus antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment Epstein-Barr virus DNA.

Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA-IgA) and viral capsid antigen (VCA-IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA-IgA and VCA-IgA in patients with NPC is less clear. We hypothesize that serum EA-IgA and VCA-IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non-metastatic NPC and undetectable pEBV DNA were included. Serum EA-IgA and VCA-IgA were determined by ELISA. After analysis, serum EA-IgA and VCA-IgA loads correlated positively with T, N, and overall stage (all P < 0.05). Serum EA-IgA was not associated with survival outcome in univariable analyses. But patients with serum VCA-IgA >1:120 had significantly inferior 5-year progression-free survival (80.4% vs 89.6%, P = 0.025), distant metastasis-free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse-free survival (88.4% vs 95.6%, P = 0.023; log-rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA-IgA became insignificant. Further analyses revealed that serum VCA-IgA was not an independent prognostic factor in early N (N0-1) or advanced N (N2-3) stage NPC. In summary, although both EA-IgA and VCA-IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA.

Prognostic value of primary gross tumor volume and standardized uptake value of 18F-FDG in PET/CT for distant metastasis in locoregionally advanced nasopharyngeal carcinoma.

Distant metastasis has become the predominant model of treatment failures in patients with locoregionally advanced nasopharyngeal carcinoma. Effort should therefore be made to stratify locoregionally advanced nasopharyngeal carcinoma patients into different groups based on the risk of metastasis to improve prognosis and tailor individualized treatments. This study aims to assess the value of primary gross tumor volume and the maximum standardized uptake value for predicting distant metastasis-free survival of patients with locoregionally advanced nasopharyngeal carcinoma. A total of 294 locoregionally advanced nasopharyngeal carcinoma patients who were identified from prospectively maintained database and underwent fluor-18-fluorodeoxyglucose positron emission tomography/computed tomography imaging before treatment were included. The maximum standardized uptake value was recorded for the primary tumor (SUVmax-P) and neck lymph nodes (SUVmax-N). Computed tomography-derived primary gross tumor volume was measured using the summation-of-area technique. At 5 years, the distant metastasis-free survival rate was 83.7%. The cut-off of the SUVmax-P, SUVmax-N, and primary gross tumor volume for distant metastasis-free survival was 8.95, 5.75, and 31.3 mL, respectively, by receiver operating characteristic curve. In univariate analysis, only SUVmax-N (hazard ratio: 7.01; 95% confidence interval: 1.70-28.87; p < 0.01) and clinical stage (hazard ratio: 3.03; 95% confidence interval: 1.67-5.47; p = 0.007) were confirmed as independent predictors of distant metastasis-free survival. A prognostic model was derived by SUVmax-N and clinical stage: low risk (SUVmax-N < 5.75 regardless of clinical stage), medium risk (stage III and SUVmax-N ≥ 5.75), and high risk (stage IV and SUVmax-N ≥ 5.75). Multivariate analysis revealed that SUVmax-N and the prognostic model remained independent prognostic factors for distant metastasis-free survival (p = 0.023 and p < 0.001, respectively), but the clinical stage became insignificant (p = 0.133). Furthermore, the adjusted hazard ratios for the prognostic model were higher than SUVmax-N (hazard ratio = 6.27 vs 5.21, respectively). In summary, compared with SUVmax-P, SUVmax-N may be a better predictor of distant metastasis-free survival for patients with locoregionally advanced nasopharyngeal carcinoma. Combining SUVmax-N with clinical stage gives a more precise picture in predicting distant metastasis.

Efficacy and safety of calcineurin inhibitor treatment for IgA nephropathy: a meta-analysis.

BACKGROUND: IgA nephropathy is the most common progressive glomerular disease to end stage renal failure worldwide. Calcineurin inhibitors (CNIs) is a selective immunosuppressant widely used in organ transplantation. The efficacy and safety of calcineurin inhibitors for the treatment of IgA nephropathy remain uncertain. METHODS: We performed a systematic literature search using the PubMed, Embase, Science Citation Index, Ovid evidence-based medicine, Chinese Biomedical Literature (CBM) and Chinese science and technology periodicals (CNKI, VIP, and Wan Fang) for randomized, controlled trials of CNIs therapy of IgA nephropathy. Complete remission rate (CR) was defined as proteinuria less than 0.5 or 0.3 g/d. Partial remission rate (PR) was defined as proteinuria reduced to at least half of the baseline measurement and an absolute value of >0.5 or 0.3 g/d. RESULTS: Seven relevant trials were conducted with 374 patients enrolled. CNIs plus medium/low-dose steroid had a higher CR (RR = 2.51 [95% CI,1.25 to 5.04], P = 0.02) compared to therapy with steroid alone or placebo, but were not significant on PR (RR = 0.87 [95% CI,0.32 to 2.38]; P = 0.78). Also, significant alterations were observed in proteinuria (weighted mean difference, -0.46 g/d,[95% CI:-0.55 to -0.24], P < 0.01) with no differences were found in serum creatinine (SCr) (weighted mean difference, 0.57,95% CI:-4.05 to 5.19; P = 0.78) and estimated glomerular filtration rate (eGFR) (weighted mean difference, 1.13,95% CI:-4.05 to 6.32; P = 0.34) level between the two groups. CNI therapy was associated with an increased risk for adverse events (RR = 2.21,95% CI:1.52 to 3.21, P < 0.01), such as gastrointestinal and neurological symptoms or hirsutism. CONCLUSIONS: CNIs might provide renal protection in patients with IgAN, but at an increased risk of adverse events. Reliably defining the efficacy and safety of CNIs in IgAN requires a high-quality trial with a large sample size.

Subdivision of M category for nasopharyngeal carcinoma with synchronous metastasis: time to expand the M categorization system.

INTRODUCTION: The current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a "catch-all" classification, covering a heterogeneous group of tumors ranging from potentially curable to incurable. The aim of this study was to design an M categorization system that could be applied in planning the treatment of NPC with synchronous metastasis. METHODS: A total of 505 NPC patients diagnosed with synchronous metastasis at Sun Yat-sen University Cancer Center between 2000 and 2009 were involved. The associations of clinical variables, metastatic features, and a proposed M categorization system with overall survival (OS) were determined by using Cox regression model. RESULTS: Multivariate analysis showed that Union for International Cancer Control (UICC) N category (N1-3/N0), number of metastatic lesions (multiple/single), liver involvement (yes/no), radiotherapy to primary tumor (yes/no), and cycles of chemotherapy (>4/≤4) were independent prognostic factors for OS. We defined the following subcategories based on liver involvement and the number of metastatic lesions: M1a, single lesion confined to an isolated organ or location except the liver; M1b, single lesion in the liver and/or multiple lesions in any organs or locations except the liver; and M1c, multiple lesions in the liver. Of the 505 cases, 74 (14.7%) were classified as M1a, 296 (58.6%) as M1b, 134 (26.5%) as M1c, and 1 was not specified. The three M1 subcategories showed significant difference in OS [M1b vs. M1a, hazard ratio (HR) = 1.69, 95% confidence interval (CI) = 1.16-2.48, P = 0.007; M1c vs. M1a, HR = 2.64, 95% CI = 1.75-3.98, P < 0.001]. CONCLUSIONS: We developed an M categorization system based on the independent factors related to the prognosis of patients with metastatic NPC. This system may be helpful to further optimize individualized care for NPC patients.

A Case of High-Altitude Renal Syndrome.

Wang, Si-Yang, Jun Liang, and Jing-Hong Zhao. A Case of High-Altitude Renal Syndrome. High Alt Med Biol. 00:000-000, 2024.-Epidemiological studies have confirmed that high-altitude exposure increases the risk of proteinuria. The concept of high-altitude renal syndrome (HARS) was proposed in 2011. HARS is a group of clinical syndromes consisting of high-altitude polycythemia, hyperuricemia, systemic hypertension, and microalbuminuria. At present, no standardized and unified treatment methods of HARS have been proposed. We report a case of HARS without other organ involvement in a young man exposed to high altitude. Decreasing the red blood cell count and hemodynamic changes as soon as possible may be of great importance for reducing proteinuria. In addition, angiotensin receptor blockers are effective in the treatment of HARS.

Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P  < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P  < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P  < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P  < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.

Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial.

BACKGROUND: The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. METHODS: We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3-4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m(2) cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0-2·27 Gy per fraction with five daily fractions per week for 6-7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60-66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m(2) adjuvant cisplatin and 800 mg/m(2) per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT00677118. FINDINGS: 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3-61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81-90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78-88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49-1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 [21%] of 205 patients treated with adjuvant chemotherapy). INTERPRETATION: Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials. FUNDING: Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010-178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).

Effects of high altitude on renal physiology and kidney diseases.

The hypobaric and hypoxic conditions of high-altitude areas exert adverse effects on the respiratory, circulatory and nervous systems. The kidneys have an abundant blood supply (20%-25% of cardiac output) and high blood flow; thus, they are susceptible to the effects of hypoxia. However, the effects of acute and chronic exposure to high altitudes on renal physiology and pathology are not fully understood. Moreover, few studies have investigated the impact of high-altitude exposure on patients with chronic kidney disease or acute kidney injury. In this review, we summarized changes in renal physiology and renal pathology due to high-altitude exposure as well as the impact of high-altitude exposure on existing kidney diseases, with the aim of informing the prevention and treatment of kidney diseases at high altitudes.