Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer.

Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.

Post hoc analysis of daratumumab plus lenalidomide, bortezomib and dexamethasone in Black patients from final data of the GRIFFIN study.

Due in part to racial disparities and underrepresentation in clinical studies, optimal therapies for Black patients with multiple myeloma remain undefined. This final analysis of GRIFFIN by race showed that the addition of daratumumab (D) to lenalidomide/bortezomib/dexamethasone (RVd) provides clinical benefit among both Black and White transplant-eligible newly diagnosed patients compared with RVd alone. However, Black patients were more likely to discontinue ≥1 drug due to treatment-emergent adverse events. In summary, these findings suggest a benefit of D-RVd front-line therapy among Black and White patients and underscore the importance of equitable treatment access for all patients.

Patient-reported symptoms before adjuvant locoregional radiotherapy for breast cancer: triple-negative histology impacts the symptom burden.

BACKGROUND: Multimodal breast cancer treatment may cause side effects reflected in patient-reported outcomes and/or symptom scores at the time of treatment planning for adjuvant radiotherapy. In our department, all patients have been assessed with the Edmonton Symptom Assessment System (ESAS; a questionnaire addressing 11 major symptoms and wellbeing on a numeric scale of 0-10) at the time of treatment planning since 2016. In this study, we analyzed ESAS symptom severity before locoregional radiotherapy. PATIENTS AND METHODS: Retrospective review of 132 patients treated between 2016 and 2021 (all comers in breast-conserving or post-mastectomy settings, different radiotherapy fractionations) was performed. All ESAS items and the ESAS point sum were analyzed to identify subgroups with higher symptom burden and thus need for additional care measures. RESULTS: The biggest patient-reported issues were fatigue, pain, and sleep problems. Patients with triple negative breast cancer reported a higher symptom burden (mean 30 versus 20, p = 0.038). Patients assigned to adjuvant endocrine therapy had the lowest point sum (mean 18), followed by those on Her-2-targeting agents without chemotherapy (mean 19), those on chemotherapy with or without other drugs (mean 26), and those without systemic therapy (mean 41), p = 0.007. Those with pathologic complete response after neoadjuvant treatment had significantly lower anxiety scores (mean 0.7 versus 1.8, p = 0.03) and a trend towards lower depression scores, p = 0.09. CONCLUSION: Different surgical strategies, age, and body mass index did not impact on ESAS scores, while the type of adjuvant systemic therapy did. The effect of previous neoadjuvant treatment and unfavorable tumor biology (triple negative) emerged as important factors associated with symptom burden, albeit in different domains. ESAS data may facilitate identification of patients who should be considered for additional supportive measures to alleviate specific symptoms.

Acute myeloid leukemia with paraneoplastic pemphigus successfully treated with a personalized antileukemic and immunosuppressive strategy.

Bullous pemphigoid (BP) is a rare blistering disease often considered a primary sign of a paraneoplastic syndrome. Retrospective studies have established its link with hematological malignancies, particularly lymphoproliferative disorders. Here, we present what we believe to be the inaugural case of successful simultaneous management of BP and de novo acute myeloid leukemia (AML) in a 28-year-old male patient. Given the rarity and severity of both conditions, our treatment strategy aimed to maximize efficacy by combining immunosuppressive therapy (initially plasmapheresis with high-dose corticosteroids, followed by anti-CD20 monoclonal antibody and intravenous immunoglobulins 2 g/m2) with lymphodepleting antileukemic chemotherapy utilizing Fludarabine (FLAG-IDA induction regimen). Following diagnosis, considering the patient's youth and the concurrent presence of two rare and potentially life-threatening diseases, we opted for an aggressive treatment. Upon achieving complete morphological remission of AML with measurable residual disease (MRD) negativity, despite incomplete resolution of BP, we proceeded with high-dose cytarabine consolidation followed by peripheral stem cell harvest and autologous stem cell transplantation (ASCT). Our conditioning regimen for ASCT involved Bu-Cy with the addition of anti-thymocyte globulins. At day + 100 post-ASCT, bone marrow evaluation confirmed morphological remission and MRD negativity. Meanwhile, BP had completely resolved with normalization of BP180 antibody levels.

Pretransplantation predictors of survival in nonremission acute myeloid leukemia treated with haploidentical transplantation using steroid-based GVHD prophylaxis.

Haploidentical hematopoietic cell transplantation (HCT) using glucocorticoids for acute graft-versus-host disease prophylaxis (GC-haplo) may become a curative treatment option for nonremission acute myeloid leukemia (AML). This retrospective study aimed to identify pre-HCT predictors of survival in a cohort of 97 nonremission AML treated with GC-haplo in Hyogo Medical University Hospital between 2010 and 2020. Relapse and primary induction failure included in 70 (72%) and 27 (28%) patients, respectively. Sixty-one patients (63%) had undergone previous HCT. Multivariate analysis revealed that ≤ 6 months' duration between first complete remission (CR1) and first relapse (Rel1) (CR1-Rel1 interval) (hazard ratio 2.11, 95% confidence interval [CI] 1.15-3.89, P = 0.016) and serum albumin before starting the conditioning treatment of ≤ 3.5 g/dL (hazard ratio 1.80, 95%CI 1.09-2.96, P = 0.022) as risk factors for overall survival. Among three groups categorized according to serum albumin and CR1-Rel1 interval, the best 3-year overall survival was observed in patients with albumin > 3.5 g/dL and CR1-Rel1 interval > 6 months or primary induction failure (50.2%, 95%CI 28.9%-68.3%, P < 0.001), revealing that survival could be predicted using albumin and past CR duration in patients with very high-risk AML not in remission before GC-haplo.

SANI clinical remission definition: a useful tool in severe asthma management.

In the field of severe asthma, the concept of disease control has recently been integrated by the one of clinical remission. With this new concept, we move on to analyze the efficacy of therapy on multiple parameters simultaneously, starting with the mandatory discontinuation of the systemic glucocorticoids, to which is added the effect on exacerbations, respiratory function, and symptoms control. The Italian severe asthma registry SANI (Severe Asthma Network Italy) drafted criteria for the definition of disease remission, allowing patients to be classified into two groups, partial and complete remission. The greater dynamism of the definition, provided by SANI, allows us to hypothesize its practical use, concerning therapy management of severe asthma patients, starting from the level of remission, with the aim to facilitate the clinical decision on replacement, continuation or modulation of patients' therapy.

Digital whole-slide imaging of changes in amyloid after peripheral blood stem cell transplantation in patients with amyloid light-chain amyloidosis.

Peripheral blood stem cell transplantation (PBSCT) has made amyloid light-chain (AL) amyloidosis treatable. After PBSCT, hematological complete remission (HCR) can be achieved, leading to improved renal prognosis. The purpose of this study was to evaluate whether whole slide imaging of biopsy samples shows a post-treatment reduction in amyloid deposits in patients with AL amyloidosis. Patients were divided into three groups: Group A (n = 8), not eligible for PBSCT and treated with other therapies; Group B (n = 11), treated with PBSCT and achieved HCR; and Group C (n = 5), treated with PBSCT but did not achieve HCR. Clinical findings and amyloid deposition in glomeruli, interstitium, and blood vessels were compared before and after treatment using digital whole-slide imaging. Proteinuria and hypoalbuminemia improved more in Group B than in the other groups, and in Group B, amyloid deposition improved more in the glomeruli than in the interstitium and blood vessels. The long-term renal and survival prognosis was better in Group B than in the other groups. PBSCT can be expected to improve long-term clinical and renal histological prognosis in patients with AL amyloidosis who achieve HCR. Amyloid disappearance from renal tissue may take a long time even after clinical HCR.

Delayed complete remission of hemifacial spasms following microvascular decompression and the implications for optimal time of revision surgery.

BACKGROUND: Microvascular decompression (MVD) is an effective method for directly treating hemifacial spasms (HFS). The timing for the consideration of failed MVD and reoperation has been paradoxical. OBJECTIVE: This study aimed to investigate the delayed complete remission of HFS in terms of prevalence rate, duration between surgery and delayed complete remission, and predictive factors. METHODS: A hundred patients with HFS who underwent MVD from 2012-2021 were enrolled in the study. All HFS occurred as a result of compression of the facial nerve by adjacent blood vessels. Clinical information, intraoperative findings, and surgical outcomes were incorporated for data analysis. RESULTS: In the first week after MVD, 67 of 100 patients achieved complete remission of HFS, while the remaining 33 had incomplete remission. In long-term follow-up, 26 individuals gradually developed delayed complete remission with a median duration of 9.1 months. Finally, 86 of 100 patients achieved complete long-term remission. Recurrent HFS and incomplete remission were found in 7 and 7 patients, respectively. Factors associated with postoperative complete remission in the first week were a severe degree of facial nerve compression (p = 0.047, OR 2.75, 95% CI 1.01-7.40), with long-term complete remission was left-sided HFS (p = 0.012, OR 5.73, 95% CI 1.47-22.36), and with the appearance of delayed complete remission was the prolonged duration of HFS at least 3 years before MVD (p = 0.046, OR 3.75, 95% CI 1.03-13.76). Transient facial paresis was found in 11% of the patients. Of them, facial nerve function recovered completely in all cases. CONCLUSIONS: A delayed complete remission of HFS could be expected in long-term follow-up after MVD and is probably related to a longer duration of HFS before surgery. Unnecessary reoperation should be avoided in the early years following the first surgery.

Systematic review and meta-analysis: Prognostic impact of time from diagnosis to treatment in patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) has been considered an oncologic emergency that requires initiation of chemotherapy immediately after diagnosis. With the introduction of novel targeted therapies, there is a potential benefit associated with delaying definitive treatment for identification of actionable therapeutic targets. Unfortunately, cytogenetic/molecular testing can take >7 days to return, and there is not a consensus regarding the prognostic impact of time from diagnosis to treatment (TDT) in AML. METHODS: A literature review and meta-analysis of studies done to date that evaluate TDT was conducted. Studies that reported baseline characteristics, TDT, and outcomes for patients with AML were selected. Outcomes included overall survival (OS), complete remission (CR), and mortality. Studies that measured CR rates within each TDT range and data to calculate odds ratios were included in the meta-analysis. The remaining outcomes were synthesized descriptively for literature review. RESULTS: Thirteen studies were identified, which comprised a total of 14,946 patients. Median TDT values were between 1 and 8 days. Several studies found a significant association between prolonged TDT and older age and lower proliferation burden. Four of 11 studies did not detect a significant relationship between TDT and OS. No studies found a significant association between TDT and early death. Six of eight studies did not find a significant association between TDT and CR rate. The meta-analysis found a significant association between prolonged TDT and decreased achievement of CR (p < .05). CONCLUSIONS: Results were highly variable but suggest it may be feasible to pursue cytogenetic/molecular testing in patients who are clinically stable, particularly in those aged 60 years and older.

Unrelated or haploidentical allogeneic hematopoietic cell transplantation in second complete remission for acute myeloid leukemia-Improved outcomes over time: A European Society for Blood and Marrow Transplantation Acute Leukemia Working Party study.

BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) is the only cure for acute myeloid leukemia (AML) in second complete remission (CR2). Patients lacking a matched sibling donor (MSD) receive transplants from matched unrelated donors (MUDs), mismatched unrelated donors (MMUDs), haploidentical (haplo) donors, or cord blood. METHODS: This is a retrospective, registry-based European Society for Blood and Marrow Transplantation study that investigates changes in patient- and transplant-related characteristics and posttransplant outcomes over time. RESULTS: We identified 3955 adult patients (46.7% female; median age, 52 years [range, 18-78 years]) with AML in CR2 first transplanted between 2005 and 2019 from a MUD 10/10 (61.4%), MMUD 9/10 (21.9%), or haplo donor (16.7%) and followed for 3.7 years. A total of 725 patients were transplanted between 2005 and 2009, 1600 between 2010 and 2014, and 1630 between 2015 and 2019. Over the three time periods, there was a significant increase in patient age (from 48.7 to 53.5 years; p < .001), use of a haplo donor (from 4.6% to 26.4%; p < .001), and use of posttransplant cyclophosphamide (from 0.4% to 29%; p < .001). There was a significant decrease in total body irradiation and in vivo T-cell depletion. In multivariate analysis, transplants performed more recently had better outcomes. Leukemia-free survival (hazard ratio [HR], 0.79; p = .002) and overall survival (HR, 0.73; p < .001) increased over time. Similarly, nonrelapse mortality (HR, 0.64; p < .001) decreased over time. We also observed better graft-vs-host disease (GVHD) rates (acute GVHD II-IV: HR, 0.78; p = .03; GVHD-free, relapse-free survival: HR, 0.69; p < .001). CONCLUSIONS: Even in the absence of an MSD, outcomes of allo-HCT in CR2 for AML have significantly improved over time, with most favorable outcomes achieved with a MUD.

Re-induction therapy in patients with acute myeloid leukemia not in complete remission after the first course of treatment.

A standard salvage regimen for patients with acute myeloid leukemia (AML) who are not in complete remission (CR) after initial induction therapy does not exist. We retrospectively investigated re-induction therapy for 151 patients with AML who did not achieve CR after the initial course between January 2014 and March 2021. The re-induction regimen did not correlate with the CR rate after the second course, whereas patients had similar 5-year overall survival (OS) and event-free survival (EFS) based on different re-induction regimens. Multivariable analysis revealed that International European Leukaemia Net (ELN) risk stratification independently predicted both OS and EFS among patients not in CR after the first course, although the re-induction regimen did not predict prognosis. Urgent salvage alloHSCT may improve the prognosis of patients with refractory AML. In summary, our study showed that the re-induction regimen did not significantly predict the prognosis of patients with AML not in CR after the first course of treatment. The development and selection of an efficient treatment algorithm for the treatment of AML remains a pressing research challenge.

Comparison of outcomes for patients with acute myeloid leukemia undergoing haploidentical stem cell transplantation in first and second complete remission.

There was no consensus on whether prognostic advantages existed when transplant conducted at first complete remission (CR1) stage than at second complete remission (CR2) stage for patients with AML who received haploidentical hematological stem cell transplantation (haplo-HSCT). In 768 consecutive AML patients who received haplo-HSCT from January 2014 to December 2017, a 1:2 ratio matched-pair analysis was performed, 69 patients who in CR2 group and 138 CR1 patients were enrolled. Hematopoietic recovery, graft versus host disease (GVHD), relapse, transplant related mortality (TRM), disease-free survival (DFS) and overall survival (OS) were compared in two groups, and further evaluated in low-, intermediate-, and high-risk subgroups. The cumulative incidences of 30-day myeloid recovery and 90-day platelet recovery were comparable in CR1 and CR2 groups. The cumulative incidences of grade II-IV and grade III-IV aGVHD were not significantly different. The cumulative incidences of relapse at 3-year and 5-year in these two groups were 12.4% versus 11.6% (P = 0.880) and 12.4% versus 17.5% (P = 0.322). The cumulative incidences of TRM at 3-year and 5-year were both 10.9% versus 23.2% (P = 0.019). The probability of DFS at 3-year and 5-year were 76.7% versus 65.2% (P = 0.029) and 76.7% versus 59.3% (P = 0.009). The probability of OS at 3-year and 5-year were 81.8% versus 68.1% (P = 0.026) and 76.7% versus 59.3% (P = 0.026). In the intermediate-risk group, TRM was lower in CR1 group, DFS and OS of CR1 group were superior to CR2 group. In conclusion, haplo-HSCT at CR1 stage was of better prognosis for intermediate-risk AML patients than at CR2 stage.

Different treatment strategies versus a common standard arm (CSA) in patients with newly diagnosed AML over the age of 60 years: a randomized German inter-group study.

A randomized inter-group trial comparing more intensive treatment strategies to a common standard arm 3 + 7 (CSA) was conducted in patients with non-M3 AML. Untreated patients ≥ 60 years were allocated to the CSA (n = 132) or to the study group arms (n = 1154) of the AMLCG (TAD/HAM versus HAM/HAM ± G-CSF followed by TAD and maintenance) and the OSHO (intermediate-dose ara-C/mitoxantrone followed by ara-C/mitoxantrone). Median age of the 1147 eligible patients was 69 (range 60-87) years. CR/CRi status at 90 days was not significantly different between the CSA (54% (95%CI: 45-64)) and the study group arms (53% (95%CI: 47-60) and 59% (95%CI: 58-63)). The five-year event-free survival (EFS) probability (primary endpoint) was 6.2% (95%CI: 2.7-14.0) in the CSA, 7.6% (95%CI: 4.5-12.8) in study group A and 11.1% (95%CI: 9.0-13.7) in B. The 5-year OS was 17.2% (95%CI: 11.0-26.9), 17.0% (95%CI: 2.0-23.9), and 19.5% (95%CI: 16.7-22.8) in CSA, study group A and B, respectively. Neither study group differed significantly from the CSA regarding EFS, OS, or relapse-free survival. In multivariate analyses, allocation to the treatment strategy was not significantly associated with the time-to-event endpoints. The evaluation of more intensive treatment strategies did not show clinically relevant outcome differences when compared to CSA.

Oncologic outcomes of watch-and-wait strategy or surgery for low to intermediate rectal cancer in clinical complete remission after adjuvant chemotherapy: a systematic review and meta-analysis.

BACKGROUND: A watch-and-wait (WW) strategy or surgery for low to intermediate rectal cancer that has reached clinical complete remission (cCR) after neoadjuvant chemotherapy (nCRT) or total neoadjuvant therapy (TNT) has been widely used in the clinic, but both treatment strategies are controversial. OBJECTIVE: The aim of this study was to compare the oncologic outcomes of a watch-and-wait strategy or a surgical approach to treat rectal cancer in complete remission and to report the evidence-based clinical advantages of the two treatment strategies. METHODS: Seven national and international databases were searched for clinical trials comparing the watch-and-wait strategy with surgical treatment for oncological outcomes in patients with rectal cancer in clinical complete remission. RESULTS: In terms of oncological outcomes, there was no significant difference between the watch-and-wait strategy and surgical treatment in terms of overall survival (OS) (HR = 0.92, 95% CI (0.52, 1.64), P = 0.777), and subgroup analysis showed no significant difference in 5-year disease-free survival (5-year DFS) between WW and both local excision (LE) and radical surgery (RS) (HR = 1.76, 95% CI (0.97, 3.19), P = 0.279; HR = 1.98, 95% CI (0.95, 4.13), P = 0.164), in distant metastasis rate (RR = 1.12, 95% CI (0.73, 1.72), P = 0.593), mortality rate (RR = 1.62, 95% CI (0.93, 2.84), P = 0.09), and organ preservation rate (RR = 1.05, 95% CI (0.94, 1.17), P = 0.394) which were not statistically significant and on the outcome indicators of local recurrence rate (RR = 2.09, 95% CI (1.44, 3.03), P < 0.001) and stoma rate (RR = 0.35, 95% CI (0.20, 0.61), P < 0.001). There were significant differences between the WW group and the surgical treatment group. CONCLUSION: There were no differences in OS, 5-year DFS, distant metastasis, and mortality between the WW strategy group and the surgical treatment group. The WW strategy did not increase the risk of local recurrence compared with local resection but may be at greater risk of local recurrence compared with radical surgery, and the WW group was significantly better than the surgical group in terms of stoma rate; the WW strategy was evidently superior in preserving organ integrity compared to radical excision. Consequently, for patients who exhibit a profound inclination towards organ preservation and the evasion of stoma formation in the scenario of clinically complete remission of rectal cancer, the WW strategy can be contemplated as a pragmatic alternative to surgical interventions. It is, however, paramount to emphasize that the deployment of such a strategy should be meticulously undertaken within the ambit of a multidisciplinary team's management and within specialized centers dedicated to rectal cancer management.

Phospholipase A2 Receptor Antibodies and Clinical Prognosis in Patients with Idiopathic Membranous Nephropathy: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor (PLA2R-ab) are considered as diagnostic biomarkers of IMN. OBJECTIVE: Here, we performed an updated meta-analysis to assess the diagnostic value of PLA2R-ab for clinical remission in IMN patients. METHOD: PubMed, Embase, and Cochrane databases were searched for relevant studies published before September 2022. Odds ratios and corresponding 95% confidence intervals were determined using a fixed or random effects model. The heterogeneity among studies was explored by subgroup analysis. RESULTS: Sixteen studies involving 1,761 IMN participants were included. There were significant differences between PLA2R-ab (+) and PLA2R-ab (-) patients in terms of complete remission (CR) and spontaneous remission. The rates of partial remission (PR) and relapse were similar between the two groups. Patients with PLA2R-ab (-) were at a higher CR rate when treated with a calcineurin inhibitor or a treatment course for 3 months and 6 months, while the spontaneous remission rate was higher in PLA2R-ab seronegative patients from Asia. However, the CR and spontaneous remission rate only significantly declined in IMN patients with the highest titer, but not a middle titer, when compared to those with the lowest titer. CONCLUSION: In contrast with previous meta-analyses, our results verified that PLA2R-ab can likely predict CR and spontaneous remission in IMN patients, instead of PR and relapse. Race, immunosuppressive agents, and duration of treatment may affect the prognostic value of PLA2R-ab. Considering that the remission rate of IMN patients with a middle level of PLA2R-ab was not different from that of patients with the lowest level, a proper cut-off value of PLA2R-ab for prognosis should be clarified.

Analysis of immunohistochemical characteristics and recurrence after complete remission with fertility preservation treatment in patients with endometrial carcinoma and endometrial atypical hyperplasia.

OBJECTIVE: To investigate the relationship between immunohistochemical characteristics and recurrence after complete remission (CR) with fertility preservation treatment in patients with endometrial cancer (EC) and endometrial atypical hyperplasia (AH). METHODS: The clinical data and immunohistochemical results of 53 patients with EC and 68 patients with AH admitted to Peking University People's Hospital from January 2010 to January 2021 were retrospectively analyzed. Patients were divided into two groups according to whether recurrence after complete remission (CR): group 1: recurrence after CR; group 2: no recurrence after CR, for statistical analysis. RESULTS: (1) The expression rate of ER in group 1 was lower than that in group 2, (P < 0.05). The expression rate of Ki-67 in group 1 was significantly higher than that in group 2, (P < 0.01). The expression rates of PR, P16, P53, and PTEN were not significantly different between the two groups (P > 0.05); (2) combination index ER/ Ki-67 row ROC curve analysis, there was a significant difference (P < 0.01), the best cut-off value was 3.55, sensitivity 0.730, specificity 1.000, Youden index 0.730. The 3-year RFS of high rate patients was 100%, and that of low rate patients was 42.3%, P < 0.01. CONCLUSIONS: The expression rate of Ki-67 is of great significance in predicting the recurrence of EC after fertility preservation therapy. The best cut-off value of combination index ER/ Ki-67 (3.55) was better than a single immunohistochemical marker in predicting recurrence of EC after fertility preservation treatment.

Prognosis of patients with endometrial cancer or atypical endometrial hyperplasia after complete remission with fertility-sparing therapy.

PURPOSE: Although many patients with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) achieve complete remission (CR) after high-dose medroxyprogesterone acetate (MPA) treatment, no consensus has been reached on management after CR. Currently, patients receive estrogen-progestin maintenance therapy, but no recommendations exist regarding the duration of maintenance therapy or whether hysterectomy should be considered. This study aimed to provide insights into the management of EC/AEH after achieving CR. METHODS: We retrospectively investigated the prognosis of 50 patients with EC or AEH who achieved CR after MPA therapy. We assessed the association between disease recurrence and clinicopathological features and the pre- and post-operative histological diagnoses of patients who underwent hysterectomy. RESULTS: The median follow-up duration was 34 months (range: 1-179 months). Recurrence was observed in 17 patients. Among the clinical characteristics investigated, only the primary disease was significantly associated with disease recurrence; patients with EC had a higher risk of recurrence than those with AEH (p = 0.037). During the observation period, 27 patients attempted pregnancy, and 14 pregnancies resulted in delivery. Patients who gave birth had significantly longer relapse-free survivals than those who did not (p = 0.031). Further, 16 patients underwent hysterectomies, and AEH was detected postoperatively in 4 of 11 patients (36.4%) with no preoperative abnormalities. CONCLUSIONS: We identified several clinical features of patients with EC and AEH after CR. Given the high probability of endometrial abnormalities detected postoperatively, hysterectomy may be considered for patients who no longer want children.

The thickness of glomerular basement membrane predicts complete remission in primary membranous nephropathy.

Objective: Glomerular basement membrane (GBM) thickening is a typical and essential histopathological characteristic for the diagnosis of primary membranous nephropathy (PMN). The present study aimed to explore the relationship between GBM thickness and treatment response in PMN patients.Methods: A total of 128 patients with nephrotic syndrome concurrent with PMN were studied. The highest GBM thickness was measured from at least five glomerular capillary loops using an electron microscope, and the mean value was obtained. Patients were categorized into three groups according to the tertiles of GBM thickness as follows: Group 1 (GBM thickness ≤ 1100 nm, n = 48), Group 2 (1100 nm < GBM thickness ≤ 1300 nm, n = 40), Group 3 (GBM thickness >1300 nm, n = 40). Clinicopathological features and treatment response were compared among the three groups. The associations of GBM thickness with complete remission (CR) were assessed by Cox proportional hazard analyses and a cubic spline curve.Results: During a median follow-up period of 25.80 months, 69 (53.9%) patients achieved CR. Kaplan-Meier analysis showed that the non-CR probability was significantly higher in the highest tertile of GBM thickness (p˂0.001). Univariate Cox proportional hazard analysis indicated that GBM thickness was associated with CR (HR per SD 0.617, 95% CI [0.471-0.809], p˂0.001). After adjusting for age, duration of PMN, estimated glomerular filtration rate (eGFR), urinary protein excretion, grade of C3 deposition, and titer of serum anti-phospholipase A2 receptor (PLA2R) antibody, GBM thickness remained an independent predictor of CR (HR per SD 0.580, 95% CI [0.436-0.772], p˂0.001). Further multivariable-adjusted restricted cubic spline analysis confirmed a significant reverse linear association between GBM thickness and CR (p for nonlinear = 0.1261).Conclusions: GBM thickness is an independent risk factor of CR. PMN patients with an increased level of GBM thickening at diagnosis have a lower probability of achieving CR.

Rituximab treatment for refractory nephrotic syndrome in adults: a multicenter retrospective study.

BACKGROUND: The treatment of refractory nephrotic syndrome (RNS) is full of challenges and the role of rituximab (RTX) is not well-established, thus this study aims to demonstrate the role of RTX in RNS. METHODS: This was a multicenter retrospective study of all adult patients receiving RTX for RNS. Patients enrolled were divided into two groups according to pathological pattern: 20 patients as a group of podocytopathy (including minimal change disease [MCD] and focal and segmental glomerulosclerosis [FSGS]), and 26 patients as membranous nephropathy (MN) group. The remission rate, relapse rate, adverse effects, and predictors of remission were analyzed. RESULTS: A total of 75 patients received RTX for RNS and 48 were available for analysis after exclusion criteria. No significant difference in the remission rate at 6 or 12 months was observed between the MCD/FSGS and MN cases (p > 0.05). The median duration of the first complete remission (CR) was 1 month in the podocytopathy group and 12.5 months in the MN group. Three relapses were associated with infection as the ultimate outcome, and 6 out of 48 remained refractory representing a response rate of 87.5% in RNS. Clinical predictors of cumulative CR were estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and mean arterial pressure (MAP) ≤103 mmHg at the beginning of therapy in patients with MN. No serious adverse effects were reported. CONCLUSIONS: RTX appears to be effective in RNS across various clinical and pathological subtypes, exhibiting a low relapse rate and minimal significant side effects in the majority of patients.

The Addition of Hypomethylating Agents to Low-Intensity Induction Chemotherapy Does Not Improve Outcomes in Elderly Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study.

Background and Objectives: This study aimed to evaluate whether the addition of hypomethylating agents (HMA) to low-intensity chemotherapy can enhance the clinical efficacy of induction treatment for elderly acute myeloid leukemia (AML) patients who are unsuitable for standard induction therapy. Materials and Methods: This study retrospectively analyzed 117 patients over 60 years old who were initially diagnosed with AML and received low-intensity induction treatment in the Department of Hematology in Anhui provincial hospital from January 2015 to December 2020. Twenty-three patients were excluded, and the remaining 94 patients were divided into two groups according to the selection of induction regimens. Results: Forty-four patients received HMA combined with low-intensity chemotherapy, and the other 50 patients received only low-intensity induction chemotherapy. Forty-three patients (45.7%) obtained complete remission (CR) after the initial induction treatment. The CR rate in the HMA plus low-intensity chemotherapy group was 34.1% (15/44), and in the single low-intensity chemotherapy group was 56.0% (28/50) (p = 0.04). The 30 days cumulative early death rates were 9.1% (95% CI: 3.5-22.4%) in the HMA plus low-intensity chemotherapy group and 6.0% (95% CI: 2.0-17.5%) in the single low-intensity chemotherapy group, respectively (p = 0.59), and the one-year cumulative relapse rates were 21.1% (95% Cl: 9.8-41.9%) and 33.3% (95% Cl: 20.3-51.5%), respectively (p = 0.80). The one-year overall survival (OS) rates for patients in the HMA plus low-intensity chemotherapy group and the single low-intensity chemotherapy group were 37.3% (95% Cl: 23.1-51.5%) and 55.4% (95% Cl: 40.5-67.9%), respectively (p = 0.098), and the one-year event-free survival (EFS) rates were 8.5% (95% Cl: 2.2-20.6%) and 20.6% (95% Cl: 9.1-35.3%), respectively (p = 0.058). Conclusions: This study showed that the addition of HMA to low-intensity induction chemotherapy does not improve prognosis in elderly AML patients who are unsuitable for standard induction chemotherapy.