Remission Rate Research Articles

The Role of Endoscopic Transsphenoidal Surgery in Microprolactinomas: A Retrospective Study

Most patients with microprolactinomas have to take dopamine agonist for a lifetime. Many of them in our center have consulted endoscopic transsphenoidal surgery as an alternative therapy. The current study is a retrospective cohort analysis of 42 patients with microprolactinoma underwent endoscopic transsphenoidal surgery between January 2010 and December 2023 by experienced neurosurgeons in our center. The mean follow-up duration was 30.17 months (range, 13.00-45.40). The short-term (postoperative day 1) remission rate was 95.24% and the long-term (over 1-year follow-up) remission rate was 92.86%. As to remission, the pattern of prolactin level changes on postoperative day 1 was significantly associated with recurrence. In hypoprolactinemia group, all 29 patients showed remission at the 1-year follow-up. In patients with normal PRL levels, 10 out of 11 patients showed remission, while 1 out of 11 patients showed recurrence at the 1-year follow-up. In hyperprolactinemia group, all 2 patients showed recurrence at the 1-year follow-up. Moreover, adenoma location was significantly associated with recurrence as well. In the recurrent group (3 patients), 2 patients belonged to the uncertain group, while the other patient belonged to the lateral group. The surgical complications were temporary and resolved shortly after surgery. According to our findings, endoscopic transsphenoidal surgery performed on patients with microprolactinomas at advanced pituitary tumor centers could be an option with high success rates and low complications. Moreover, improving MRI imaging techniques and/or multidisciplinary team discussion before surgery for microprolactinoma could improve tumor remission after surgery.

Clinical effect of hepatic artery interventional embolization and chemotherapy and its influence on P16 protein expression in patients with liver cancer.

To investigate clinical effects of hepatic artery interventional embolization chemotherapy (TACE) for primary hepatocellular carcinoma (PHC). 73 patients with PHC in our hospital from January 2017 to January 2018 were selected and divided into 37 cases in study group and 36 cases in control group by random number table method. The control group received only ultrasound-guided microwave ablation treatment, and the study group received TACE treatment again before surgery based on control group. The expression levels of cancer antigen 125 (CA125), alpha-fetoprotein (AFP), multiple tumor suppressors 1 (P16) proteins, and cancer antigen 19-9 (CA19-9) were compared between the two groups at different time periods after treatment, and the remission rate (ORR), control rate (DCR), complication rate at 3months after treatment and survival rate at 3years after treatment were compared. After 1year of treatment, ORR, DCR, and P16 protein levels in the study group were higher than those in the control group (P < 0.05), and differences were statistically significant; CA125, CA19-9, and AFP levels in study group were lower than those in the control group (P < 0.05), and differences were statistically significant. The regression equation showed that long-term survival rate of both groups showed decreasing trend over time, while long-term survival rate of study group was always higher than that of the control group. Comprehensive intervention for hepatic artery interventional chemoembolization in patients with primary hepatocellular carcinoma is more effective, which can effectively reduce incidence of complications and adverse effects in patients and help shorten treatment time of hepatic artery interventional chemoembolization in patients.

Kidney Failure in Pauci-immune Crescentic Glomerulonephritis: Rationale for Immunosuppression to Improve Kidney Outcome.

Pauci-immune crescentic glomerulonephritis is the hallmark finding in ANCA-associated vasculitis (AAV) when the kidneys are affected. The rationale for immunosuppression in AAV is based on the underlying autoimmune nature of the disease. Overall remission rates, kidney outcomes, and the burden of disease have greatly improved since the discovery of various immunosuppressive therapies, but relapses remain common, and a significant proportion of patients continue to progress to end-stage kidney disease. Here, we review the role of immunosuppressive therapies for the treatment of pauci-immune crescentic glomerulonephritis. Besides the recognized role of B and T cells in the pathogenies of AAV, the focus on the contribution of inflammatory cytokines, neutrophil extracellular traps (NETs), and the complement system allowed the discovery of new therapies. Specifically, the C5a receptor blocker (avacopan) has been approved as a glucocorticoid-sparing agent. Additionally, based on observational data, more clinicians are now using combination therapies during the induction phase. There is also an evolving understanding of the role of plasma exchange in removing ANCA antibodies. Furthermore, the recent development of risk score systems provides physicians with valuable prognostic information that can influence decisions on immunosuppression, although future validation from larger cohorts is needed. The over-activation of various immune pathways plays a significant role in the pathogenesis of pauci-immune crescentic glomerulonephritis in AAV. Immunosuppression is, therefore, an important strategy to halt disease progression and improve overall outcomes. Relapse prevention while minimizing adverse events of immunosuppression is a major long-term goal in AAV management.

Long-Term Clinical and Sustained REMIssion in Severe Eosinophilic Asthma Treated With Mepolizumab: The REMI-M Study

Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. While mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission. To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months. The REMI-M is a retrospective, real-world, multicenter study that analyzed 303 severe eosinophilic asthma patients who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroids (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period. Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months, based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% to 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastro-esophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent. This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics.

Evolving Horizons in Pediatric Leukemia: Novel Insights, Challenges, and the Journey Ahead.

Pediatric leukemia, encompassing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia, remains a formidable challenge despite significant treatment advancements. This review examines recent developments in immunotherapy, chemotherapy, and bone marrow transplantationfor pediatric leukemia through a comprehensive analysis of recent literature, focusing on critical studies and clinical trials. Immunotherapy, including monoclonal antibodies, such as blinatumomab and inotuzumab ozogamicin, and chimeric antigen receptor T-cell therapies, such as tisagenlecleucel and brexucabtagene autoleucel, have demonstrated promising results in relapsed or refractory B-cell ALL (B-ALL), achieving notable remission rates with manageable side effects. Chemotherapy continues to be the primary treatment, utilizing multiphase regimens tailored to individual risk profiles. Bone marrow transplantation, especially allogeneic stem cell transplantation, offers potential cures for high-risk or relapsed cases, though it poses risks including graft-versus-host diseaseand infections. Despite these advancements, treatment resistance, toxicity, and accessibility persist. This review also discusses the long-term outcomes among pediatric leukemia survivors, focusing on late-onset side effects associated with treatments such as chemotherapy and bone marrow transplantation, encompassing secondary malignancies, organ dysfunction, and neurocognitive impacts. Ongoing research and clinical trials are crucial to refine these therapies, enhance their efficacy, and reduce adverse effects, ultimately improving young patients' survival and quality of life.

Etiology, Clinical Characteristics and Prognosis of Secondary Hemophagocytic Syndrome

To understand the etiology, clinical characteristics and prognosis of secondary hemophagocytic syndrome (HLH), so as to improve the understanding of HLH and reduce the rates of misdiagnosis and missed diagnosis of HLH. A retrospective study was conducted to analyze the cause, clinical characteristics, laboratory findings, therapy and outcomes of 75 adult patients with secondary HLH admitted to our hospital from January 2015 to December 2021. Follow-up continued until the last discharge time. Among 75 patients, infection-related HLH was the most common (45.33%), followed by lymphoma-related HLH (17.33%). Fever was the most common clinical manifestation (97.67%). Laboratory indicators such as NK cell activity (98.31% low or absent), sCD25 (93.22% increased), and serum ferritin (94.44% elevated) had higher sensitivity in diagnosis. By comparing the clinical manifestations and laboratory indicators of HLH patients with different causes, sex, lymph node enlargement and bone marrow morphology were more valuable for the diagnosis of primary disease (all P <0.05). By comparing the treatment and clinical outcomes of HLH patients with different causes, the highest clinical remission rate (83.3%) was achieved in patients with autoimmune disease-related HLH treated with hormone+cyclosporine (P <0.05). The overall 12-month survival rate of all patients was 26.7%, in which the infection-related HLH was the lowest (14.7%) while autoimmune disease-related HLH was the highest (63.6%). The causes and clinical characteristics of adult secondary HLH are varied, with poor prognosis and heterogeneity in disease severity. It is important to identify HLH cause early for diagnosis and needed to further understand HLH.

Preoperative treatment with dopamine agonist therapy influences surgical outcome in prolactinoma: a retrospective single-center on 159 patients

IntroductionProlactinoma account to the most common pituitary adenomas and current therapy regime constitutes of dopamine agonist therapy (DA) and surgery in selected cases [17]. Due to tumor fibrosis induced by previous DA therapy, surgical removal can be challenging though. Therefore, this study investigates how preoperative DA usage influences perioperative treatment and surgical outcome in prolactinoma and aims to ascertain whether a specific subgroup of prolactinoma patients could derive greater benefit from exclusive surgical intervention.MethodsWe retrospectively analyzed n = 159 surgically treated and histologically confirmed prolactinomas in the sella region from 2013–2022 in our institution. Clinical, radiological and surgical features were analyzed. Univariate and multivariate analyses were performed.ResultsOut of total of 159 prolactinoma patients, 83.6% received previous treatment with DA followed by surgery, while only 16.4% received exclusive surgery. Both groups presented similar initial tumor volumes (1.9cm3 vs. 1.5cm3, p = 0.59) and equal preoperative prolactin levels (PRL) (199.7 µg/l vs. 191.0 µg/l, p = 0.44). Surgical procedures took significantly longer when patients received prior DA treatment (79 min. vs. 70 min., p = 0.0479). Six months after surgery, pretreated patients revealed significantly higher PRL compared to non-treated (107 g/l vs. 8.64 µg/, p = 0.0009). Additionally, untreated microprolactinoma presented a remission of 100%, whereas pretreated exhibited a remission rate of 88.75%.ConclusionThe current study demonstrates that prior DA treatment is associated with significantly longer surgeries, higher recurrence rates and lower rates of normalization of PRL levels after surgery, particularly in microprolactinomas and support the latest recommendations of the Pituitary Society's Consensus Statement 2023, which favors the option of surgery alone as first-line therapy for microprolactinomas.

Clinical Study of Venetoclax Combined with Azacitidine in the Treatment of Patients with Adult Acute Myeloid Leukemia

To evaluate the efficacy and side effects of venetoclax combined with azacitidine chemotherapy in the treatment of previously untreated adult patients with acute myeloid leukemia(AML). A retrospective analysis was performed on 48 untreated adult AML patients admitted to the Department of Hematology, Affiliated Hospital of Jinggangshan University from January 2020 to December 2022. Among them, 26 patients received venetoclax combined with azacitidine chemotherapy (observation group), and 22 patients received daunorubicin plus cytarabine chemotherapy (control group). The differences in complete response (CR) rate, objective response rate (ORR), progressionfree survival (PFS), overall survival(OS) and adverse reactions (AR) were compared between the two groups. There was no significant difference in age, sex ratio, absolute value of trilineage cell and proportion of bone marrow primordial cells between the two groups before treatment (all P >0.05). The CR rate and the ORR rate of the observation group was significantly higher than that of the control group (P < 0.05). After treatment, there were no significant difference in the adverse reactions such as myelosuppression, granulocytosis, secondary infection, mucosal damage, liver and kidney damage, cardiotoxicity and gastrointestinal toxicity between the two groups (P >0.05). The median PFS and the median OS of the observation group were significantly better than those of the control group (P < 0.05). The remission rate of venetoclax combined with azacitidine was higher than that of conventional chemotherapy in previously untreated adult acute myeloid leukemia. Venetoclax combined with azacitidine chemotherapy could reduce hematologic related side reactions and prolong the remission period and survival of AML patients.

Outcome of endoscopic transsphenoidal surgery for acromegaly: Comparison of using and not using the floor standing pneumatic powered endoscope-holder system

IntroductionEndoscopic transsphenoidal surgery can be performed by two surgeons, including an endoscopist (PE/2S), and by a single surgeon with an endoscope-holder system (PE/1S + H). We analyzed the surgical outcome, and outcome predictors in acromegaly patients in endoscopic transsphenoidal surgery using floor standing pneumatic endoscope-holder system. MethodsEndoscopic transsphenoidal surgery was performed with PE/1S+H (n = 51) and PE/2S (n = 20). Postoperative remission was evaluated by the 2010 consensus criteria for acromegaly. We compared the surgical results of PE/2S style and PE/1S+H style, and investigated the factors associated with favorable surgical outcomes. ResultsThere was no difference in clinical background between the PE/2S and the PE/1S + H groups. The remission rates for PE/2S and PE/1S+H were 65.0% and 82.4%, respectively, with no significant difference (p = 0.128). In consecutive 71 cases, statistically useful predictors of remission were low preoperative growth hormone (GH) level (<12 ng/mL), low Knosp grade (0–2), and low revised Knosp grade (0–3A). In the conventional Knosp grade 0–2 and 3/4, the sensitivity was 0.76 and the specificity was 0.81. In the revised Knosp grade 0–3A and 3B/4, the sensitivity was 0.96 and the specificity was 0.44. ConclusionThe outcome of GH-producing pituitary neuroendocrine tumors surgically removed by PE/1S+H could be almost equivalent to that by PE/2S. Preoperative low GH level and Knosp grades, including revised Knosp grades, are useful preoperative predictors for surgical remission of acromegaly.

Outcome of bariatric surgery in patients with unexpected liver cirrhosis: A multicenter study from China

Background and aimsLiver cirrhosis is a complex disease that may result in increased morbidity and mortality following bariatric surgery (BS). This study aimed to explore the outcome of BS in patients with unexpected cirrhosis, focusing on postoperative complications and the progression of liver disease. MethodsA retrospective study of bariatric patients with cirrhosis from four centers in China between 2016 and 2023 was conducted, with follow-up for one year after BS. The primary outcome was the safety of BS in patients with unexpected cirrhosis, while the secondary outcome was the metabolic efficacy of BS in this group postoperatively. ResultsA total of 47 patients met the study criteria, including 46 cases of Child-Pugh class A cirrhosis and 1 case of Child-Pugh B. Pathological examination confirmed nodular cirrhosis in 21 patients (44.68%), pseudolobule formation in 1 patient (2.13%), lipedema degeneration with inflammatory cell infiltration in 3 patients (6.38%), and chronic hepatitis in 1 patient (2.13%). The average percentage of total weight loss was 29.73 ± 6.53% at one year postoperatively. During the 30-day postoperative period, the complication rate was 6.38%, which included portal vein thrombosis, gastrointestinal bleeding, and intra-abdominal infection. Moreover, no cases of liver decompensation or mortality were reported during the follow-up period. The remission rates of comorbidities among 41 patients one year after surgery were as follows: dyslipidemia 100%, type 2 diabetes 82.61%, hypertension 84.62%, and obstructive sleep apnea syndrome 85.71%. ConclusionsBS can be safely performed in patients with unexpected cirrhosis in the compensated stage of liver disease, with low postoperative morbidity and no mortality observed during one-year follow-up.

Immunosuppression for adult steroid-dependent or frequently relapsing nephrotic syndrome: A systematic review and meta-analysis.

There is limited evidence on which immunosuppressive agents produce the best outcomes for adult patients with steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS). This review compares the remission rate and adverse effects of various immunosuppressants used. Studies of adult patients with biopsy-proven SDNS/FRNS, administered any immunosuppressive agents and reported complete remission results as one of the clinical outcomes were included. Articles were independently screened by two researchers. ROBINS-I was used for risk of bias assessment. Random-effects model was used for statistical analysis and corresponding 95% confidence intervals (CIs) were calculated. 574 patients across 28 studies were included in the analysis. Patients receiving rituximab have a complete remission rate of 89% (95% CI = 83% to 94%; τ2 = 0.0070; I2 = 62%; overall p < 0.01, low certainty) and adverse event rate of 0.26, cyclosporine (CR 40%; 95% CI = 21% to 59%; τ2 = 0.0205; I2 = 55%; overall p = 0.08, low certainty), tacrolimus (CR 84%; 95% CI = 70% to 98%; τ2 = 0.0060; I2 = 33%; overall p = 0.21, moderate certainty), mycophenolate mofetil (CR 82%; 95% CI = 74% to 90%; τ2 < 0.0001; I2 = 15%; overall p = 0.32, moderate certainty) and cyclophosphamide (CR 79%; 95% CI = 69% to 89%; τ2 = 0; I2 = 0%; overall p = 0.52, moderate certainty). Among the commonly used immunosuppressive agents, only rituximab has a statistically significant effect in achieving complete remission among patients with SDNS/FRNS and has a relatively good safety profile, but this is limited by low quality of evidence with high degree of heterogeneity causing a lack of statistical power.

Shedding more than weight: Metabolic and bariatric surgery and the journey to insulin independence in insulin-treated type 2 diabetes

BackgroundType 2 diabetes (T2D) imposes a significant health burden, necessitating lifelong pharmacological interventions, with insulin being one of the cornerstone therapies. However, these regimens are associated with health risks and psychological stressors. This study aimed to examine the rates of insulin-treated T2D remission and cessation or reduction in the dosage of insulin therapy after metabolic and bariatric surgery (MBS). MethodsThis was a retrospective analysis of patients with a preoperative diagnosis of insulin-treated T2D who underwent primary laparoscopic sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) with a minimum of 3 and up to 5 years of follow-up. The average daily dose for each type of insulin, measured in units, was calculated at annual intervals. ResultsAmong 287 patients included, 201 (70%) underwent RYGB, 66 (23%) underwent SG, and 20 (7%) underwent BPD/DS. The average follow-up period was 4.6 ± 0.7 years. At 5 years follow-up, the mean total weight loss was the highest in the BPD/DS subgroup at 37.5% ± 11.6%. Insulin usage decreased significantly from complete dependency at baseline to 36.2% just 1 year postoperatively, and the use of noninsulin antidiabetic drugs decreased from 79.4% initially to 26.1%. These results were sustained throughout the study period. The subgroup analysis indicated that, 5 years after surgery, T2D remission was the highest after BPD/DS (73.7%) compared with RYGB (43.2%) and SG (23.3%) (P < .001). ConclusionMBS is a transformative approach for achieving significant remission in insulin-treated T2D and reducing insulin requirements. Our findings reinforce the efficacy of these surgical interventions, particularly highlighting the promising potential of procedures that bypass the proximal small intestine, such as BPD/DS and RYGB.

MEST C Score and Treatment Response in IgA Nephropathy in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

IgA nephropathy is the leading cause of primary glomerulonephritis worldwide. The Oxford classification can predict IgA nephropathy prognosis through renal biopsy however its applicability to the Nepalese population remains unexplored. This study aimed to evaluate the MEST-C score and treatment response in patients with IgA nephropathy. This descriptive cross-sectional study was conducted at a tertiary care center from November 2021 to November 2022 after obtaining ethical approval [IRC-193(6-11)t2078/079]. Total population sampling was done. Fifty-two consenting patients aged 16 or older with confirmed IgA nephropathy were included, excluding those with liver disease or expected survival of less than six months. The study assessed the MEST-C score, demographic factors, and clinical parameters. Data analysis was done using Statistical Package of Social Sciences. Among 52 patients with segmental glomerulosclerosis (S1), 11 (24.44%) achieved complete remission, 30 (66.67%) partial remission, and 5 (11.11%) progressed to end-stage renal disease. In those with tubular atrophy/interstitial fibrosis (T1), 1 (5.88%) achieved complete remission, 13 (76.47%) partial remission, and 4 (23.53%) progressed to end-stage renal disease. For glomerular crescents (C1), 9 (47.37%) achieved complete remission, 9 (47.37%) partial remission, and 1 (5.26%) progressed to end-stage renal disease. IFTA% of 0-25% had complete remission in 15 (46.88%). Among the two patients with IFTA% ≥50%, one (50%) developed end-stage renal disease and the other achieved partial remission. The S1 and T1/2 components of the MEST-C score had higher rates of partial remission and progression to end-stage renal disease, while other indices showed mixed results. The risk of failing to achieve complete increased with an IFTA of more than 25%.

Mucosal and Transmural Healing and Long-term Outcomes in Crohn's Disease.

Healing in Crohn's disease is complex and difficult to measure due to incongruencies between clinical symptoms and disease states. Mucosal healing (MH) and transmural healing (TH) are increasingly used to measure clinical improvement in Crohn's disease, but definitions of MH and TH can vary across studies, and their relationship to long-term outcomes is not clear. To address this knowledge gap, we performed a systematic literature review (SLR) to examine studies measuring MH and TH in Crohn's disease. Database records from 2012 to 2022 were searched for real-world evidence and interventional studies that reported the association of MH or TH with clinical, economic, or quality of life outcomes of adult patients with Crohn's disease. A total of 46 studies were identified in the systematic literature review, representing a combined patient population of 5530. Outcomes of patients with MH were reported by 39 studies; of these, 14 used validated scales for endoscopic assessment. Thirteen studies reported outcomes of patients with TH. Among studies that examined the outcomes of patients with and without MH or TH, patients with healing generally experienced improved clinical outcomes and reduced healthcare resource utilization, including fewer hospitalizations and surgeries and improved rates of clinical remission. This was especially true for patients with TH. Mucosal and transmural healing are associated with positive long-term outcomes for adult patients with Crohn's disease. The adoption of standardized measures and less invasive assessment tools will maximize the benefits of patient monitoring.

Outcomes of Bariatric Surgery in Patients with Schizophrenia.

Outcomes of bariatric surgery (BS) in patients with schizophrenia are poorly understood. We aimed to analyze the effects of BS in patients with schizophrenia (SZ) or schizoaffective disorder (SZA). This was a multicenter, retrospective case-control study in patients with SZ or SZA who had undergone BS in seven public referral hospitals in Spain. Controls without psychiatric comorbidity were selected in a 1:4 ratio. Detailed clinical and biochemical data were collected preoperatively and at 12, 24, 36, 48, and 60 months after BS. Twenty patients with SZ (n = 15; 75%) or SZA (n = 5; 25%) and 80 matched controls were studied. There were no differences between patients and controls concerning the evolution of the percentage of total weight loss. The remission rate of the main comorbidities was similar between groups except for hypertension, which was lower in patients with a psychotic disorder from year 3. There were no mortalities within 30 days of surgery in either group. The psychiatric medication burden did not change during follow-up. BS is safe and effective in carefully selected patients with SZ. The course of the psychiatric disease does not seem to be worsened by the procedure.

Cell-Based Therapy and Genome Editing as Emerging Therapeutic Approaches to Treat Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints. Although much remains unknown about the pathogenesis of RA, there is evidence that impaired immune tolerance and the development of RA are related. And it is precisely the restoration of immune tolerance at the site of the inflammation that is the ultimate goal of the treatment of RA. Over the past few decades, significant progress has been made in the treatment of RA, with higher rates of disease remission and improved long-term outcomes. Unfortunately, despite these successes, the proportion of patients with persistent, difficult-to-treat disease remains high, and the task of improving our understanding of the basic mechanisms of disease development and developing new ways to treat RA remains relevant. This review focuses on describing new treatments for RA, including cell therapies and gene editing technologies that have shown potential in preclinical and early clinical trials. In addition, we discuss the opportunities and limitations associated with the use of these new approaches in the treatment of RA.

Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

Systematic review: Methotrexate-A poorly understood and underused medication in inflammatory bowel disease.

Methotrexate, an immunosuppressant used for the treatment of inflammatory bowel disease (IBD) for over 30 years, remains underused compared to thiopurines. To review the efficacy, safety, optimal dosing and delivery regimens of methotrexate in adults with IBD. We conducted a systematic review of studies involving patients with IBD treated with methotrexate from inception to August 2023. All studies were included from the MEDLINE database via PubMed. For Crohn's disease, we included eight randomised controlled trials (RCTs) and 17 observational studies. Parenteral methotrexate effectively increased remission rates in steroid-dependent patients at 25 mg/week for 16 weeks and at 15 mg/week for maintenance. Methotrexate can be used in combination with anti-tumour necrosis factor (TNF) agents to reduce immunogenicity. Data comparing thiopurines and methotrexate remain scarce. For ulcerative colitis (UC), we included five RCTs and 10 observational studies were included; there was no evidence to support the use of methotrexate in (UC). We extracted safety data from 17 studies; mild-to-moderate adverse effects were common. The incidence of liver fibrosis or cirrhosis was low. Methotrexate is effective at inducing and maintaining remission in steroid-refractory Crohn's disease and can reduce anti-TNF-induced immunogenicity when used in combination therapy. Data regarding tolerance and safety are reassuring. These findings challenge preconceived ideas on methotrexate and suggest that it is a valid first-line conventional option for the treatment of mild-to-moderate Crohn's disease.

Treatment of Membranous Nephropathy in Chinese Patients: Comparison of Rituximab and Intravenous Cyclophosphamide with Steroids

Introduction: Previous studies have shown that rituximab (RTX) and cyclic oral corticosteroid-cyclophosphamide (CTX) regimens have similar effects on primary membranous nephropathy (PMN). However, no studies have compared RTX with an intravenous CTX regimen, which is more commonly used in China and requires fewer cumulative CTX doses. Methods: We prospectively assigned 141 PMN patients with baseline proteinuria ≥4 g/24 h, serum albumin <30 g/L, and eGFR ≥30 mL/min × 1.73 m2 despite at least 3 months of treatment with ACEI and/or ARB to the RTX group (375 mg/m2 per injection per week × 4 injections) or to the CTX group (prednisone 0.8 mg/kg/day and intravenous CTX 500 mg/m2 per month until the total dose reached 6–8 g). The primary endpoint was defined as a combination of partial remission or complete remission at 12 months. Results: By the end of 12 months, 43 of 70 patients (61.43%) in the RTX group and 54 of 71 patients (76.06%) in the CTX group reached the primary endpoint (p = 0.06). Significantly fewer patients in the RTX group achieved complete remission than the CTX group (14.29% vs. 33.80%, p = 0.01). The adverse events rate was similar between the RTX group and the CTX group (28.57% vs. 40.85%, p = 0.13). In subgroup analysis, we found that fewer patients from the RTX group achieved the primary endpoint than the CTX group (48.65% vs. 74.29%, p = 0.03) among patients with massive proteinuria (urine protein ≥8 g/24 h). During the observational phase, 61 patients in the RTX group and 58 in the CTX group completed 24 months of follow-up, exhibiting similar remission rates (RTX vs. CTX: 75.41% vs. 68.97%, p = 0.54). Conclusions: Our results show that the intravenous CTX regimen has similar safety and efficacy with higher rates of early complete remission than RTX in the treatment of PMN patients.

Antidepressant class and concurrent rTMS outcomes in major depressive disorder: a systematic review and meta-analysis

Repetitive transcranial magnetic stimulation (rTMS) is frequently used as an adjunctive treatment with antidepressants for depression. We aimed to evaluate the clinical efficacy and safety of antidepressant classes when administered concurrently with rTMS for the management of major depressive disorder (MDD). In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from inception to April 12th 2024 for terms relating to medication, depression, and rTMS and appraised by 2 independent screeners. All randomized clinical trials that prospectively evaluated a specific antidepressant adjunctively with sham rTMS as a control in MDD were included. The study was registered with PROSPERO (CRD42023418435). The primary outcome measure assessed symptomatic improvement measured by formal depression scales. We used a random-effects model with pooled Standardized Mean Differences (SMDs) and log odds ratios (OR). All studies were assessed for their methodological quality and bias using the Cochrane Collaboration Risk of Bias tool version 2 (RoB2). 14 articles from 5376 identified studies were included in the systematic review and meta-analysis. There was only sufficient trial data to evaluate the effects of rTMS and combination therapy with selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). Across studies, 848 participants (mean [SD] age:41.1 [18.7] years for SSRIs, 51.8 [3.8] years for SNRIs) prospectively examined the efficacy of antidepressant medication with rTMS. Combining rTMS with SSRIs led to significantly lower depression scores, (SMD [CI] of-0.65 [-0.98,-0.31], p=0.0002, I2=66.1%), higher response (OR=0.97 [0.50, 1.44], p<0.0001, I2=25.33%) and remission rates (OR=1.04 [0.55, 1.52], p<0.0001, I2=0.00%) than medication with sham rTMS. No additive benefit was found for SNRIs with rTMS (SMD of 0.10 [-0.14, 0.34], p=0.42, I2=0.00%; OR=0.12 [-0.39, 0.62], p=0.64, I2=0.00%; OR=-0.31 [-0.90, 0.28], p=0.86, I2=39.9%). The overall risk of bias for the included studies ranged from low to high, with 1 study having a high risk of bias. The combination of rTMS with SSRIs, but not SNRIs, significantly reduced depression severity, increasing response and remission rates. Some analyses demonstrated high heterogeneity, which was influenced by an SSRI trial with a high effect size. Overall, these results suggest that not all antidepressant combination therapies are alike, and SSRIs should be considered when initiating rTMS. Donald T. Stuss Young Investigator Research Innovation Award from the Sandra Black Centre for Brain Resilience & Recovery and the Harquail Centre for Neuromodulation through the Sunnybrook Foundation.