Neoadjuvant Glucocorticoids Facilitate Resection in Advanced B-Type Thymomas: A Propensity-Matched Analysis of Surgical and Survival Outcomes.

Glucocorticoid benefits the ventilatory function of severe/critical COVID-19 patients

Glucocorticoids accelerate the reduction of disease severity and biochemical parameters in drug-induced liver injury: Assess the causal relationship using the updated RUCAM scale.

ABSTRACTBackgroundFew studies have evaluated the treatment of immunoglobulin A nephropathy (IgAN) patients with nephrotic syndrome (NS) and mesangioproliferative glomerulonephritis (MPGN). The aim of this study was to compare the therapeutic effects of oral glucocorticoids (GCS) combined with intravenous cyclophosphamide (CTX) and oral GCS alone in the treatment of the MPGN-IgAN patients with NS.MethodsBiopsy-proven primary IgAN patients who were aged ≥14 years at diagnosis, had coexistent NS and MPGN and estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2, and were treated by oral GCS combined with intravenous CTX or oral GCS alone for 6–12 months were retrospectively included. The patients in the GCS + CTX (prednisone 0.6–0.8 mg/kg/day and intravenous CTX 0.6–1.0 g monthly) or GCS (prednisone 0.8–1 mg/kg/day) group were rather matched at a 1:1 ratio on key characteristics by propensity score matching. The primary outcome was defined as either complete remission or partial remission at Month 24. The secondary outcome was a composite renal endpoint defined as a 50% decline in eGFR, doubling of serum creatinine or progression to end-stage kidney disease.ResultsAmong the 146 IgAN patients who met the inclusion criteria, 42 patients were enrolled in the GCS + CTX group, and 42 patients were enrolled in the GCS group after propensity score matching. The clinical and histological parameters were similar between the two groups. Remission occurred more frequently in the GCS + CTX group at Month 6 (88.1% vs 52.4%, P < 0.001), Month 12 (88.1% vs 56.1%, P = 0.001) and Month 24 (85.0% vs 47.5%, P < 0.001) than in the GCS group. Moreover, subgroup analysis revealed that the higher response rate at Month 24 in the GCS + CTX group than in the GCS group was also present in different subgroups defined by sex, age, eGFR or Oxford MEST-C. Notably, we found that eGFR decreased at a lower rate in patients from the GCS + CTX group than in patients from the GCS group [eGFR slope: 0.05(–3.09, 3.67) vs –2.56 (–11.30, 0.86) mL/min/1.73 m2/year, P = 0.03]. Based on multivariate Cox regression analysis, GCS + CTX treatment was found to be independently associated with a decrease in risk for the composite endpoint after adjusted by the International Risk Prediction Score with race (hazard ratio = 0.17, 95% confidence interval 0.04–0.83, P = .03). There was no significant difference in adverse events (50.0% vs 42.9%, P = 0.51) or serious adverse events (7.1% vs 11.9%, P = .71) between the two groups.ConclusionsOral GCS combined with intravenous CTX is superior to GCS alone in treating MPGN-IgAN patients combined with NS. As the retrospective design and small sample size, our findings need to be validated by a prospective study.

Objective To investigate the effect of glucocorticoid (GC) on interleukin (IL)-33 expression in esophageal carcinoma model mice. Methods A total of 18 BALB/c mice were randomly divided into three groups such as Model group, GC group and control group. The mice in Model group drank the concentration of 100 μg/ml 4NQO solution for 16 weeks, then drank sterilized water for injection to 24 weeks; The mice in GC group were injected Dexamethasone (400 μg/mouse) into abdominal cavity for 24 weeks on the basis of the mice in Model group; The mice in Control group drank propylene glycol solution for 16 weeks, then drank sterilized water for injection to 24 weeks. All of the mice were taken blood from tail vein every four weeks. Serum levels of IL-33 were detected by enzyme linked immunosorbent assay (ELISA) method. All mice were sacrificed after 24 weeks and then the quality of intact esophagus were weighed and compared. The expression of IL-33 and ST2 protein in esophageal tissues was detected by Western blotting, and the staining of IL-33 was observed by immunohistochemistry method. Results The esophageal weight in Model group, GC group and Control group was (4.75±1.78), (2.06±0.02) and (0.08±0.01) g, respectivetly. The differences was significantly between the each group (P<0.05). The expression of IL-33 and ST2 protein, the serum level of IL-33 in Model group were significantly higher than those in GC group and Control group. The differences were statistically significant (all P<0.05). The expression of IL-33 and ST2 protein, the serum level of IL-33 in GC group were significantly higher than those in Control group. The differences were also statistically significant (all P<0.05). IL-33 staining was the most frequent in the cytoplasm of epithelial cells of esophageal mucosa in Model group A, followed by GC and Control group. Conclusion IL-33 has a significant correlation with esophageal carcinoma and GC can inhibit tumor growth by inhibiting IL-33/ST2 signal transduction pathway. Key words: Esophageal carcinoma; Interleukin-33/ST2; Glucocorticoid

The adoption of colorectal endoscopic submucosal dissection (ESD) is still limited in the West. A recent randomized trial showed that ESD is more effective and only slightly riskier than piecemeal endoscopic mucosal resection; reproducibility outside expert centers was questioned. We evaluated the results according to the annual case volume in a multicentric prospective cohort. Between September 2019 and September 2022, colorectal ESD was consecutively performed at 13 participating centers classified as low volume (LV), middle volume (MV), and high volume (HV). The main procedural outcomes were assessed. Multivariate and propensity score matching analyses were performed. Three thousand seven hundred seventy ESDs were included. HV centers treated larger and more often colonic lesions than MV and LV centers. En bloc , R0, and curative resection rates were 95.2%, 87.4%, and 83.2%, respectively, and were higher at HV than at MV and LV centers. HV centers also achieved a faster dissection speed. Delayed bleeding and surgery for complications rates were 5.4% and 0.8%, respectively, without significant differences. The perforation rate (overall: 9%) was higher at MV than at LV and HV centers. Lesion characteristics, but not volume center, were independently associated with both R1 resection and perforation. However, after propensity score matching, R0 rates were significantly higher at HV than at LV centers, and perforation rates were significantly higher at MV than at HV centers. Colorectal ESD can be successfully implemented in the West, even in nonexpert centers. However, difficult lesions must still be referred to experts.

Objective: To investigate the efficacy and safety of adrenocorticotropic hormone (ACTH) in children with frequently relapsing or steroid-dependent nephrotic syndrome. Methods: The clinical data of 38 children with frequently relapsing or steroid-dependent nephrotic syndrome who were admitted to the Department of Nephrology, the Children Hospital, Zhejiang University School of Medicine from January 2015 to December 2020 were retrospectively analyzed. The general information, clinical manifestations, laboratory data of the children and follow-up (till 12 months after treatment) were collected. The patients were divided into ACTH group and Glucocorticoid (GC) group according to treatment plan. Cumulative remission, average recurrence rate, GC dosage, height and weight change and peripheral blood CD19+B lymphocyte count were compared between the two groups to evaluate the efficacy and adverse reactions of ACTH. Fisher's exact test, t test or rank sum test was used for comparison between groups. Results: Among the 38 patients, 28 were male and 10 were female, aged 84 (24, 180) months; 19 were in ACTH group and 19 were in GC group. The cumulative remission rate of 12 months in ACTH group was higher than that in GC group (9/19 vs. 2/19,χ²=6.81,P=0.009), the average recurrence rate was lower than that in GC group ((0.7±0.8) vs. (1.7±1.1) times, t=-3.27, P=0.011), and the average dosage of GC was lower than that in GC group ((0.27±0.16) vs. (0.51±0.27) mg/(kg·d), t=-3.21, P=0.014). The increase in height was higher than that in the GC group (4 (3,5) vs. 3 (2, 3) cm/year, Z=2.58, P=0.010), and the peripheral blood CD19+B lymphocyte count was lower than that in the GC group ((223±149)×106 vs. (410±213)×106/L,t=-3.35, P=0.009). In safety, 19 cases had transient decreased urine volume, 7 cases had hyperglycemia, and 3 cases had hypertension during the infusion of ACTH, which could be relieved after drug withdrawal. Conclusion: ACTH has a better effect on children with frequently relapsing or steroid-dependent nephrotic syndrome, which can improve cumulative sustained remission rate, lower relapses rate and decrease the dosage of GC, with good safety.

Therapeutic Advances in Pancreatic Cancer

Objective: To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer. Methods: A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models. Results: Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 (P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC,n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC,n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) (P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months,P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months,P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant (P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors (P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively (P<0.01). Conclusion: Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective To study the effects of small-dose glucocorticoid (GC) on glucocorticoid receptor (GR) and cellular immune function in critical patients.Methods Forty ICU critical patients admitted in Shanghai Changzheng Hospital from March 2007 to March 2009 were enrolled in the study and were divided into GC group and non-GC group according to the use or absence of GC.Blood samples were collected at days 1,7 and 10 after GC treatment to detect GR binding affinity of mononuclear leukocytes (MNLs) and polymorphonuclear leukocytes (PMLs) in the peripheral blood and the CD4/CD8 ratio in the T lymphocytes.The method of GC use was that the hydrocortisone was given intravenously at a dose of 100 mg every eight hours.Results GR binding capacity of MNLs at day 1 and 7 showed no statistical difference between the GC and non-GC groups.GR binding capacity of MNLs in the GC group was lower at day 1 and was much lower at day 7 (P ＜ 0.05 ).However,in the non-GC group,it was lower at day 1,but showed significant improvement at day 7 ( P ＜ 0.05 ).The change of GR binding capacity of PMLs was similar to that of MNLs.There was no significant difference of CD4/CD8 ratio between the GC and non-GC group at day 1.The ratio of CD4/CD8 in the non-GC group was significantly higher than that in the GC group at day 10 (P ＜0.05).CD4/CD8 ratio in the GC group showed a slight reduction at day 10,with no significant difference from that at day 1.While,the non-GC group showed a significant increase of CD4/CD8 ratio at day 10 as compared with that at day 1 (P ＜ 0.05 ).Conclusion Low-dose GC plays some role in the negative feedback regulation of GR binding capacity of peripheral blood leukocytes and in the inhibition of cellular immune function. Key words: Glucocorticoids; Receptors,glucocorticoid; Immunity

No study has shown the oncologic non-inferiority of robotic pancreatoduodenectomy (RPD) versus open pancreatoduodenectomy (OPD) for pancreatic cancer (PC). This is a single institution propensity score matched study comparing RPD and ODP for resectable PC, based on factors predictive of R1 resection (≤ 1mm). Only patients operated on after completion of the learning curve in both procedures and for whom circumferential margins were assessed according to the Leeds pathology protocol were included. The primary study endpoint was the rate of R1 resection. Secondary study endpoints were as follows: number of examined lymph nodes (N), rate of perioperative transfusions, percentage of patients receiving adjuvant therapies, occurrence of local recurrence, overall survival, disease-free survival, and sample size calculation for randomized controlled trials (RCT). Factors associated with R1 resection were tumor diameter, number of positive N, N ratio, logarithm odds of positive N, and duodenal infiltration. The matching process identified 20 RPDs and 24 OPDs. All RPDs were completed robotically. R1 resection was identified in 11 RPDs (55.0%) and in 10 OPDs (41.7%) (p = 0.38). There was no difference in the rate of R1 at each margin as well as in the proportion of patients with multiple R1 margins. RPD and OPD were also equivalent with respect to all secondary study endpoints, with a trend towards lower rate of blood transfusions in RPD. Based on the figures presented herein, a non-inferiority RCT comparing RPD and OPD having the rate of R1 resection as the primary study endpoint requires 3355 pairs. RPD and OPD achieved the same rate of R1 resections in resectable PC. RPD was also non-inferior to OPD with respect to all secondary study endpoints. Because of the high number of patients required to run a RCT, further assessment of RPD for PC would require the implementation of an international registry.

Effectiveness and safety of tripterygium glycosides tablet for lupus nephritis: a systematic review and Meta-analysis.

Endoscopic submucosal dissection for treatment of gastric subepithelial tumors (with video)

R0 resection rates (complete tumour removal with negative resection margins) in pancreatic cancer are 70-80 per cent when a 0-mm margin is used, declining to 15-24 per cent with a 1-mm margin. This review evaluated the R0 resection rates according to different margin definitions and techniques. Three databases (MEDLINE from 1946, PubMed from 1946 and Embase from 1949) were searched to mid-October 2014. The search terms included 'pancreatectomy OR pancreaticoduodenectomy' and 'margin'. A meta-analysis was performed with studies in three groups: group 1, axial slicing technique (minimum 1-mm margin); group 2, other slicing techniques (minimum 1-mm margin); and group 3, studies with minimum 0-mm margin. The R0 rates were 29 (95 per cent c.i. 26 to 32) per cent in group 1 (8 studies; 882 patients) and 49 (47 to 52) per cent in group 2 (6 studies; 1568 patients). The combined R0 rate (groups 1 and 2) was 41 (40 to 43) per cent. The R0 rate in group 3 (7 studies; 1926 patients) with a 0-mm margin was 72 (70 to 74) per cent The survival hazard ratios (R1 resection/R0 resection) revealed a reduction in the risk of death of at least 22 per cent in group 1, 12 per cent in group 2 and 23 per cent in group 3 with an R0 compared with an R1 resection. Local recurrence occurred more frequently with an R1 resection in most studies. Margin clearance definitions affect R0 resection rates in pancreatic cancer surgery. This review collates individual studies providing an estimate of achievable R0 rates, creating a benchmark for future trials.

R1 resection in pancreatic cancer has significant impact on long-term outcome in standardized pathology modified for routine use

ObjectivesTo compare the efficacy of tacrolimus (TAC) plus glucocorticoids (GCs) with that of TAC plus mycophenolate mofetil (MMF) and GCs for the induction of remission in proliferative lupus nephritis (LN).MethodsThis multicentre cohort study, designed as a target trial emulation, included patients with biopsy-proven proliferative LN who received TAC-based induction therapy. Patients were classified into the TAC + GC and TAC + MMF + GC groups. The primary outcome was total renal response at 12 months, which was defined as a complete or partial renal response. To address baseline imbalances between the groups, inverse probability of treatment weighting (IPTW) was applied. Binary logistic regression was used to estimate the odds ratio (OR) for the renal response.ResultsIn total, 115 patients (48 with TAC + GC and 67 with TAC + MMF + GC) were included in the study. A 12-month total renal response was achieved in 16 (33.3%) patients in the TAC + GC group and 40 (59.7%) patients in the TAC + MMF + GC group (p = .009). After IPTW adjustment, the TAC + MMF + GC group showed significantly higher 12-month total renal response (IPTW-adjusted OR 2.84 [1.31-6.35]). Adverse drug reactions occurred in 7 patients in the TAC + GC group and 11 patients in the TAC + MMF + GC group.ConclusionsIn patients with proliferative LN, TAC + MMF + GC therapy was associated with a significantly higher 12-month renal response than TAC + GC. These findings support TAC + MMF + GC as the preferred TAC-based induction regimen for proliferative LN.