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Objectives: The purpose of this study was to compare the effectiveness of the combination of venetoclax and hypomethylating agents with the HAG regimen. Methods: We studied 52 cases of newly diagnosed AML and 26 cases of relapsed refractory AML, (including AML patients with treatment-related and ELN-adverse risk disease (n = 50)). These patients were treated with venetoclax and hypomethylating agents and HAG regimens, respectively. Results: Twenty-nine patients newly diagnosed with acute myeloid leukemia were treated with VEN-HMA (venetoclax-hypomethylating agent), while 23 patients were treated with HAG. The median age of the VEN-HMA group was 70 years, while the HAG group had a median age of 69 years. The VEN-HMA group achieved a significantly higher rate of complete remission (82.7%) compared to the cohort treated with the HAG regimen (21.7%) (P < 0.001). At the same time, the VEN-HMA group exhibited a significant survival advantage compared to the HAG treatment group(HR = 0.328, 95%CI: 0.158-0.683, P = 0.003). In patients with relapsed and refractory acute myeloid leukaemia, 43.8% of patients in the VEN-HMA treatment group achieved complete remission, which was similar to the 50% in the HAG treatment group (P > 0.99). The median overall survival was similar between the VEN-HMA and HAG groups, with 4 and 3.67 months, respectively (P = 0.290). Conclusions: In conclusion, our analyses indicated that VEN-HMA resulted in better therapeutic outcomes compared to HAG for newly diagnosed AML patients, with higher rates of complete remission and overall survival. In relapsed/refractory AML patients, there was no significant difference in the efficacy of the two treatments and further studies with larger sample sizes are warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In patients with steroid-resistant nephrotic syndrome (SRNS), the presence of monogenic variants influences therapeutic strategies. Large cohort studies reported the detection of monogenic variants in approximately 30% of patients with SRNS. However, these cohorts included many patients, such as those with symptomatic proteinuria, who did not meet the strict diagnostic criteria for pediatric nephrotic syndrome (NS). Therefore, we investigated the proportion of causative monogenic variants detected in patients who strictly met the diagnostic criteria of SRNS and explored their clinical characteristics. Methods: We examined pediatric SRNS cases with genetic analysis conducted in our hospital. Cases satisfying all of the following criteria were included: (1) age at onset 1–18 years, (2) serum albumin at onset ≤ 2.5 g/dl, (3) persistent heavy proteinuria, and (4) no complete remission after 4 weeks of steroid monotherapy. Results: The proportion of detected monogenic variants was 12% (22/185) among all patients. The proportion was only 7% (9/129) in patients with edema at disease onset compared with 38% (9/24) in those without (p < 0.0001). Monogenic variants were rare in patients with acute kidney injury associated with NS (1% (1/11)) or a history of complete remission (4% (2/51)). Conclusions: Our study revealed a monogenic cause in 12% of individuals with strictly defined SRNS, a much smaller proportion than previously reported. The presence or absence of edema at the onset was an important factor to distinguish SRNS with monogenic cause from SRNS without. Our results provide further evidence of the SRNS types attributable to monogenic causes. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Data Sources Study Eligibility Criteria Methods Results Conclusion Little scientific evidence exists on maternal and fetal outcomes in aplastic anemia (AA) during pregnancy.The review was conducted to assess the maternal and fetal outcomes due to AA during pregnancy.Web of Science, EMBASE, PubMed, Scopus, Cochrane CENTRAL, and registries until May 5, 2024.Studies (prospective, retrospective cohort, cross‐sectional, one arm, survey, follow‐up studies) evaluating AA during pregnancy were searched as per PROSPERO registered protocol (CRD42024506668). Case reports, case series, expert opinion letters, and studies assessing less than or equal to 10 pregnant women were not considered. The primary outcome was the prevalence of preeclampsia in AA pregnancies. The secondary outcomes included spontaneous abortion, preterm premature rupture of membranes, premature rupture of membranes, fetal growth restriction, type of delivery, intrauterine fetal death, maternal and neonatal mortality, and pre and post‐pregnancy remission status comparison.The quality of research was checked using the New Castle‐Ottawa risk‐of‐bias tool. A meta‐analysis model with a random effect distribution, coupled with meta‐regression, sensitivity analysis, and publication bias assessment, was used in the statistical software R. Standard Equator network study reporting guidelines were followed.Seven (one prospective and six retrospective cohort) studies included patients with confirmed AA diagnosis in 248 pregnancies. The pooled prevalence of preeclampsia was 13% (95% CI, 8%–20%). Heterogeneity was low in the present meta‐analysis (I2 = 26%). The secondary outcome evaluation showed a pooled prevalence of 5% (95% CI, 3%–11%) for spontaneous abortion, 4% (95% CI, 1%–11%) for preterm premature rupture of membranes, 10% (95% CI, 3%–28%) for premature rupture of membranes, 6% (95% CI, 3%–11%) for fetal growth restriction, 5% (95% CI, 2%–13%) for intrauterine fetal death, 12% (95% CI, 5%–26%) for post‐partum hemorrhage, 74% (95% CI, 45%–91%) for intrapartum transfusion requirement, and 55% (95% CI, 27%–80%) for the cesarean delivery opting. The maternal mortality in pregnancies with AA was 4% (95% CI, 0.01–0.14), whereas neonatal mortality was 7% (95% CI, 0.03–0.18). The odds of AA complete remission were better in pre‐pregnancy than post‐pregnancy (OR = 0.36; 95% CI = 0.08–1.66), although the results remain insignificant. The leave‐one‐out sensitivity analysis did not change the pooled estimates for the primary outcome.A risk of developing preeclampsia was observed in every eighth pregnant woman with an AA diagnosis. AA remission status might worsen after undergoing pregnancy, considering the significant obstetric morbidity and mortality burden. [ABSTRACT FROM AUTHOR]

Background Neoadjuvant therapy leads to a clinical complete response in a considerable proportion of patients with locally advanced rectal cancer, allowing for possible nonoperative management. The presence of mucin on magnetic resonance imaging (MRI) after neoadjuvant therapy leads to uncertainty about residual disease and appropriateness of a watch-and-wait strategy in patients with no evidence of disease on proctoscopy (endoscopic clinical complete response). Methods MRI reports for locally advanced rectal cancer patients seen between July 2016 and January 2020 at Memorial Sloan Kettering Cancer Center were queried for presence of mucin in the tumor bed on MRI following neoadjuvant therapy. Clinicodemographic, pathologic, and outcome data were compiled and analyzed. Results Of 71 patients with mucin on posttreatment MRI, 20 had a clinical complete response, and 51 had abnormalities on endoscopy and/or physical exam. One patient with a clinical complete response opted out of watch-and-wait; thus, 19 (27%) patients entered watch-and-wait, and 52 (73%) patients were planned for surgery (non–watch-and-wait). Of the 19 watch-and-wait patients, 15 (79%) have had no local regrowth with median follow-up of 50 months (range = 29-76 months), while 4 (21%) experienced regrowth between 9 and 29 months after neoadjuvant therapy. Of the 52 patients who were planned to have surgery (non–watch-and-wait), 49 underwent resection while 3 developed metastatic disease that precluded curative-intent surgery. Of the 49 patients who underwent surgery, 5 (10%) had a pathologic complete response (including the patient with an endoscopic clinical complete response). Conclusions The presence of mucin after neoadjuvant therapy for locally advanced rectal cancer does not preclude watch-and-wait management in otherwise appropriate candidates who achieve an endoscopic clinical complete response. [ABSTRACT FROM AUTHOR]

• Tocilizumab (TCZ) shows a rapid clinical and analytical improvement in GCA-patients. • There is an uncoupling between clinical and EULAR remission and imaging remission. • TCZ may prevent aneurysm development in GCA-patients, but more studies are needed. Aortitis in Giant Cell Arteritis (GCA-aortitis) is a frequent complication that may lead to aneurysms. Tocilizumab (TCZ) was approved in GCA, but the efficacy in GCA-aortitis and aneurysms has not been analyzed to date. Our aim was to assess the effectiveness and safety of TCZ in a wide series of GCA-aortitis and aneurysms. Multicentre observational study with GCA-aortitis treated with TCZ. GCA was diagnosed by: a) ACR criteria, b) temporal artery biopsy, and/or c) imaging techniques. Aortitis was diagnosed mainly by PET/CT. Main outcomes were EULAR and imaging remission. Others were clinical remission, analytical normalization, corticosteroid-sparing effect, and the prevention and improvement of aneurysms. 196 patients with GCA-aortitis treated with TCZ. After 6 months, 72.2% reached EULAR remission but only 12% an imaging remission; increasing up-to 81.4% and 31.8%, respectively, at 24 months. A rapid clinical remission, ESR and CRP normalization was observed in 47.4%, 84.3% and 55.6%, at 1 month, increasing to 89.6%, 85.3% and 80.3% at 24 months, respectively. Aneurysms were present in 10 (5%) patients. Five of them required early surgery, while 3 others enlarged. No patient on TCZ therapy developed aneurysms during follow-up. In patients with GCA-aortitis treated with TCZ, a rapid and maintained clinical and analytical improvement was observed. However, there was an uncoupling between clinical and EULAR remission with imaging remission. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Standard treatment for adults with acute myeloid leukemia (AML) involves anthracycline and cytarabine, while alternative regimens are necessary for elderly and frail patients. This study aims to compare the effectiveness and safety of various induction regimens in AML patients. PATIENTS AND METHODS: The retrospective study included 130 adult AML patients treated at a tertiary care center from January 2014 to December 2022. Patients received one of the following induction regimens: anthracycline and cytarabine (n = 82), azacitidine and venetoclax (n = 11), etoposide and cytarabine (n = 22), or reduced-dose anthracycline and cytarabine (n = 15). Data on demographics, clinical characteristics, treatment-related toxicities, and infectious complications were collected. Outcomes included overall survival and remission rates. RESULTS: The anthracycline and cytarabine regimen demonstrated the highest overall survival rate, although remission rates did not significantly differ among the treatment groups. Patients receiving azacitidine and venetoclax experienced a significantly longer duration of neutropenia. The use of antiviral prophylaxis increased over the study period, reflecting improved management strategies. Infection remained the leading cause of mortality. CONCLUSIONS: Effective management of prolonged neutropenia and infections is crucial for improving patient outcomes. Future research should focus on optimizing prophylactic and infection treatment strategies to further enhance survival in AML. [ABSTRACT FROM AUTHOR]

Background: Achieving first complete remission with induction chemotherapy (ICT) for acute myeloid leukemia (AML) correlates with patient's prognosis. This study aimed to determine the correlation between oxidative stress and the outcome of ICT in AML patients. Methods: A total of 195 AML patients underwent initial ICT at the Longyan First Affiliated Hospital of Fujian Medical University from 06-11-2018 to 12-30-2023. Three weeks after ICT, patients were divided into two groups, CR (complete remission) and PR (partial remission), by detecting blood parameters and bone marrow cells. Serum oxidative stress-related factors, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and growth/differentiation factor-15 (GDF15) activities or levels were measured to assess the diagnostic value of these factors as a means of diagnosing the efficacy of ICT in patients. Factors affecting PR after initial ICT were analyzed. Results: Patients in the PR group had higher levels of oxidative stress three weeks after initial ICT. Compared with the CR group, patients in the PR group had elevated levels of MDA and GDF15 and reduced activities of SOD, GSH-Px, and T-AOC. Serum MDA levels (AUC 0.709; 95% CI. 0.618 - 0.781) and the combination of multiple indicators (AUC 0.791; 95% CI. 704 - 0.851) had diagnostic value for the efficacy of AML patients undergoing ICT. Serum MDA and GDF15 exceeding cutoff values were risk factors for PR in AML patients undergoing ICT, as were serum SOD and T-AOC below cutoff values. Preoperative malnutrition was associated with PR in patients. Conclusions: Serum oxidative stress-related factors in AML patients are helpful in detecting the efficacy of ICT. Oxidative stress in response to ICT is useful for characterizing the efficacy in AML patients after ICT. [ABSTRACT FROM AUTHOR]

Abstract Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09–0.19) for MCD, 0.33 (0.23–0.40) for FSGS, and 0.20 (0.14–0.30) for MN. FENa were 0.24 (0.09–0.68), 1.03 (0.50–2.14), and 0.78 (0.41–1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97–3.81] and HR 1.93 [95% CI 1.46–2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome.

Abstract Objective To investigate the efficacy and safety of belimumab in the treatment of systemic lupus erythematosus (SLE) in a real-world setting and provide a valuable reference for clinical treatment. Methods In this retrospective study, 101 patients with SLE who came to our hospital from March 2020 to September 2022, 56 of whom with lupus nephritis (LN), were selected. All patients received belimumab in combination with standard of care(SoC)therapy regimen for more than 52 weeks and their clinical/laboratory data, assessment of disease activity, glucocorticoids dosage and occurrence of adverse events were recorded. Lupus Low Disease Activity State (LLDAS) and DORIS remission as a primary goal in the treatment of SLE. The groups were classified according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K): SLEDAI-2 K

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09–0.19) for MCD, 0.33 (0.23–0.40) for FSGS, and 0.20 (0.14–0.30) for MN. FENa were 0.24 (0.09–0.68), 1.03 (0.50–2.14), and 0.78 (0.41–1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97–3.81] and HR 1.93 [95% CI 1.46–2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Background Acute leukemia is a heterogeneous group of malignancies characterized by the rapid proliferation of immature blood cells. This study aims to compare the efficacy and safety of two different regimens of combination chemotherapy in patients diagnosed with acute leukemia. Materials and Methods A total of 120 patients with acute leukemia were randomly assigned to two treatment groups: Regimen A (cytarabine and daunorubicin) and Regimen B (cytarabine, daunorubicin, and etoposide). Patients were evaluated based on complete remission rates, overall survival, and adverse effects over a 12-month period. Results The results indicated that Regimen A achieved a complete remission rate of 70% (42 out of 60 patients), while Regimen B showed a higher rate of 80% (48 out of 60 patients). The median overall survival was 14 months for Regimen A and 18 months for Regimen B. Adverse effects were comparable, with Grade 3 or higher toxicities observed in 30% of patients in Regimen A and 25% in Regimen B. Conclusion Both regimens demonstrated significant efficacy in treating acute leukemia, with Regimen B showing superior remission rates and overall survival. Further studies are needed to confirm these findings and optimize treatment protocols. [ABSTRACT FROM AUTHOR]

Kaposi’s sarcoma (KS) is a soft tissue lesion that resembles a hyperpigmented angiosarcoma and is typically associated with human herpesvirus 8 (HHV-8) infection. It is most frequently observed in immunocompromised patients, particularly those with AIDS, and is also referred to as HIV-associated Kaposi’s sarcoma (AIDS-KS). The disease progresses rapidly, is challenging to manage, and has a high mortality rate. This case report presents a patient with AIDS-KS who experienced relapse after chemotherapy with anthracyclines. Subsequent chemotherapy with the same method had no significant effect. However, complete remission was achieved after the addition of a programmed cell death protein 1(PD-1) inhibitor, as confirmed by pathological biopsy. The PD-1 inhibitor was well-tolerated and had few adverse effects. It also helped to improve the immune reconstitution of the patient. The report highlights the remarkable efficacy of the PD-1 inhibitor in treating AIDS-KS. This provides case support for PD-1 inhibitors for AIDS-KS.

Objectives: The purpose of this study was to compare the effectiveness of the combination of venetoclax and hypomethylating agents with the HAG regimen.Methods: We studied 52 cases of newly diagnosed AML and 26 cases of relapsed refractory AML, (including AML patients with treatment-related and ELN-adverse risk disease (n = 50)). These patients were treated with venetoclax and hypomethylating agents and HAG regimens, respectively.Results: Twenty-nine patients newly diagnosed with acute myeloid leukemia were treated with VEN-HMA (venetoclax-hypomethylating agent), while 23 patients were treated with HAG. The median age of the VEN-HMA group was 70 years, while the HAG group had a median age of 69 years. The VEN-HMA group achieved a significantly higher rate of complete remission (82.7%) compared to the cohort treated with the HAG regimen (21.7%) (P 0.99). The median overall survival was similar between the VEN-HMA and HAG groups, with 4 and 3.67 months, respectively (P = 0.290).Conclusions: In conclusion, our analyses indicated that VEN-HMA resulted in better therapeutic outcomes compared to HAG for newly diagnosed AML patients, with higher rates of complete remission and overall survival. In relapsed/refractory AML patients, there was no significant difference in the efficacy of the two treatments and further studies with larger sample sizes are warranted.

Objective: This study aims to assess the impact of the metabolic risk score (MRS) on time to achieve complete remission (CR) of fertility-sparing treatments for atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) patients. Methods: Univariate and multivariate cox analyses were employed to identify independent risk factors affecting the time to CR with patients at our center. These factors were subsequently incorporated into receiver operator characteristic curve analysis and decision curve analysis to assess the predictive accuracy of time to CR. Additionally, Kaplan--Meier analysis was utilized to determine the cumulative CR rate for patients. Results: The 173 patients who achieved CR following fertility preservation treatment (FPT) were categorized into three subgroups based on their time to CR (<6, 6-9, >9 months). Body mass index (hazard ratio [HR]=0.20; 95% confidence interval [CI]=0.03, 0.38; p=0.026), MRS (HR=0.31; 95% CI=0.09, 0.52; p=0.005), insulin resistance (HR=1.83; 95% CI=0.05, 3.60; p=0.045), menstruation regularity (HR=3.77; 95% CI=1.91, 5.64; p=0.001), polycystic ovary syndrome (HR=-2.16; 95% CI=-4.03, -0.28; p=0.025), and histological type (HR=0.36; 95% CI=0.10, 0.62; p=0.005) were identified as risk factors for time to CR, with MRS being the independent risk factor (HR=0.29; 95% CI=0.02, 0.56; p=0.021). The inclusion of MRS significantly enhanced the predictive accuracy of time to CR (area under the curve [AUC]=0.789 for Model 1, AUC=0.862 for Model 2, p=0.032). Kaplan--Meier survival curves revealed significant differences in the cumulative CR rate among different risk groups. Conclusion: MRS emerges as a novel evaluation system that substantially enhances the predictive accuracy for the time to achieve CR in AEH and early EC patients seeking fertility preservation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Introduction This study investigated the efficacy and safety of neoadjuvant chemotherapy for locally advance penile squamous cell carcinoma for which current evidence is lacking. Methods Included patients had locally advanced penile squamous cell carcinoma with clinical lymph node metastasis treated with at least 1 dose of neoadjuvant chemotherapy prior to planned consolidative lymphadenectomy. Objective response rates were assessed using Response Evaluation Criteria in Solid Tumors v1.1. The primary and secondary outcomes were overall survival and progression-free survival, estimated by the Kaplan–Meier method. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events v5.0. Results A total of 209 patients received neoadjuvant chemotherapy for locally advanced and clinically node-positive penile squamous cell carcinoma. The study population consisted of 7% of patients with stage II disease, 48% with stage III, and 45% with stage IV. Grade 2 treatment-related adverse events occurred in 35 (17%) patients, and no treatment-related mortality was observed. Of the patients, 201 (97%) completed planned consolidative lymphadenectomy. During follow-up, 106 (52.7%) patients expired, with a median overall survival of 37.0 months (95% confidence interval [CI] = 23.8 to 50.1 months) and median progression-free survival of 26.0 months (95% CI = 11.7 to 40.2 months). Objective response rate was 57.2%, with 87 (43.2%) having partial response and 28 (13.9%) having a complete response. Patients with objective response to neoadjuvant chemotherapy had a longer median overall survival (73.0 vs 17.0 months, P  < .01) compared with those who did not. The lymph node pathologic complete response rate was 24.8% in the cohort. Conclusion Neoadjuvant chemotherapy with lymphadenectomy for locally advanced penile squamous cell carcinoma is well tolerated and active to reduce the disease burden and improve long-term survival outcomes. [ABSTRACT FROM AUTHOR]

Background Surrogate endpoints for overall survival in patients with resectable non–small cell lung cancer receiving neoadjuvant therapy are needed to provide earlier treatment outcome indicators and accelerate drug approval. This study's main objectives were to investigate the association among pathological complete response, major pathological response, event-free survival and overall survival and to determine whether treatment effects on pathological complete response and event-free survival correlate with treatment effects on overall survival. Methods A comprehensive systematic literature review was conducted to identify neoadjuvant studies in resectable non–small cell lung cancer. Analysis at the patient level using frequentist and Bayesian random effects (hazard ratio [HR] for overall survival or event-free survival by pathological complete response or major pathological response status, yes vs no) and at the trial level using weighted least squares regressions (hazard ratio for overall survival or event-free survival vs pathological complete response, by treatment arm) were performed. Results In both meta-analyses, pathological complete response yielded favorable overall survival compared with no pathological complete response (frequentist, 20 studies and 6530 patients: HR = 0.49, 95% confidence interval = 0.42 to 0.57; Bayesian, 19 studies and 5988 patients: HR = 0.48, 95% probability interval = 0.43 to 0.55) and similarly for major pathological response (frequentist, 12 studies and 1193 patients: HR = 0.36, 95% confidence interval = 0.29 to 0.44; Bayesian, 11 studies and 1018 patients: HR = 0.33, 95% probability interval = 0.26 to 0.42). Across subgroups, estimates consistently showed better overall survival or event-free survival in pathological complete response or major pathological response compared with no pathological complete response or no major pathological response. Trial-level analyses showed a moderate to strong correlation between event-free survival and overall survival hazard ratios (R 2 = 0.7159) but did not show a correlation between treatment effects on pathological complete response and overall survival or event-free survival. Conclusion There was a strong and consistent association between pathological response and survival and a moderate to strong correlation between event-free survival and overall survival following neoadjuvant therapy for patients with resectable non–small cell lung cancer. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient's complete remission has persisted for 20 months after HSCT. [ABSTRACT FROM AUTHOR]

Background We conducted a systematic review and meta-analysis to examine outcomes of patients with endometrial intraepithelial neoplasia treated with oral progestins or a levonorgestrel-releasing intrauterine device (IUD). Methods We conducted a systematic review across 5 databases to examine outcomes of progestational treatment (oral progestins or levonorgestrel-releasing IUD) for patients with endometrial intraepithelial neoplasia. The primary outcome was the best complete response rate within 12 months of primary progestational treatment. Sensitivity analyses were performed by removing studies with extreme effect sizes. Secondary outcomes included the pooled pregnancy rate. Results We identified 21 eligible studies, including 824 premenopausal patients with endometrial intraepithelial neoplasia, for our meta-analysis. Among these, 459 patients received oral progestin, and 365 patients received levonorgestrel-releasing IUD as a primary progestational treatment. The pooled best complete response proportion within 12 months was 82% (95% confidence interval [CI] = 69% to 91%) following oral progestin treatment and 95% (95% CI = 81% to 99%) following levonorgestrel-releasing IUD treatment. After removing outlier studies, the pooled proportion was 86% (95% CI = 75% to 92%) for the oral progestin group and 96% (95% CI = 91% to 99%) for the levonorgestrel-releasing IUD group, with reduced heterogeneity. The pooled pregnancy rate was 50% (95% CI = 35% to 65%) after oral progestin and 35% (95% CI = 23% to 49%) after levonorgestrel-releasing IUD treatment. Conclusions This meta-analysis provides data on the effectiveness of oral progestins and levonorgestrel-releasing IUD treatment within 12 months of treatment among premenopausal patients with endometrial intraepithelial neoplasia. Although based on small numbers, the rate of pregnancy after treatment is modest. These data may be beneficial for selecting progestational therapies that allow fertility preservation for patients with endometrial intraepithelial neoplasia. [ABSTRACT FROM AUTHOR]

Background RECIST criteria for progressive disease, partial response, and complete response, reflecting +20%, −30%, and −100% tumor size changes, respectively, are critical outcome variables in oncology clinical trials. Herein, we evaluated post-immunotherapy tumor size change correlation with outcomes. Methods We used a unique clinical trial data resource, a multicenter basket trial in patients with rare solid tumors treated with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) between 2017 and 2023 (National Cancer Institute/Southwest Oncology Group-sponsored DART trial [NCT02834013]) (open at 1083 sites at its peak). Outcome associations were evaluated by survival analysis techniques including Martingale residuals. Results In 638 evaluable patients, we found strong linear relationships between percent change in tumor measurement up to a 40%-50% increase and progression-free (PFS) and overall survival (OS) (both Cox regression P  < .001; landmark analyses based on day 65). Pearson R correlation between survival estimates and tumor change category were −0.94, −0.89, and −0.89 (PFS) and −0.84, −0.90, and −0.90 (OS) for median, 6-month (PFS), and 1-year (OS) and for 1-year (PFS) and 2-year (OS) estimates. Conclusions Percent change in tumor measurement per RECISTv1.1 (the sum of longest dimensions of target lesions) has a linear association with PFS and OS up to a 40% to 50% increase in tumor measurement in this cohort of patients with rare cancers who received combination immune checkpoint blockade. Quantitative first scan tumor measurement changes include important information to evaluate the potential efficacy of a therapy beyond the proportion of patients who achieve an objective response. [ABSTRACT FROM AUTHOR]

Background: In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its efficacy in terms of the criteria for clinical remission in the short and long term has become of interest. Objective: We aimed to evaluate the effect of mepolizumab in the achievement of clinical remission after 3 years of administration. Methods: In this study, 71 patients who continued mepolizumab for 3 years were assessed for clinical remission according to six different published sets of remission criteria. Results: According to the criteria, 39–52% of patients experienced complete remission in the first year, increasing to 51–73% at 3 years. By classifying patients according to partial and complete remission criteria, proposed by the SANI, we observe 22% of patients in partial remission at one year, achieving complete remission after three years. The baseline factors associated with earlier remission were a higher FEV1, if we consider classifications requiring an FEV1 ≥ 80%, a low OCS dose, and low FeNO levels, in the patients requiring FEV1 stabilization. Conclusions: Clinical remission is possible for patients treated with mepolizumab. The observations at three years compared with the first year indicated that the factors negatively affecting remission delayed rather than prevented it. Earlier treatment could increase the chances of remission. [ABSTRACT FROM AUTHOR]

The use of metal-on-metal bearing couples in total hip arthroplasty can lead to an increased release of metal ions, particularly cobalt and chromium over time. This can lead to local and systemic metallosis, which has cytotoxic, genotoxic, and immunotoxic effects and can cause a host of secondary disorders. We describe the case of a 37-year-old female patient that was diagnosed with warm-antibody autoimmune hemolytic anemia (WAIHA) one and a half years after bilateral large-diameter head metal-on-metal total hip arthroplasty. For 11 years, it was refractory to all therapy, including splenectomy and rituximab, requiring long-term oral prednisone for disease control. Ultimately, systemic metallosis and periprosthetic joint infection were diagnosed, requiring explantation of the prostheses. By the sixth week postoperatively, she experienced complete spontaneous remission of her WAIHA. In conclusion, WAIHA can be associated with systemic metallosis in patients with metal-on-metal prosthetic joint replacements. Both hematologists and orthopedic surgeons should be aware of this.

Pancreatic cancer (PC) is one of the most malignant tumors in digestive system due to its highly invasive and metastatic properties. At present, conventional treatment strategies for PC show the limited clinical efficacy. Therefore, novel effective therapeutic strategies are urgently needed. Here, we report a case of complete remission of advanced PC induced by claudin18.2-targeted CAR-T cell therapy. The patient was a 72-year-old man who was diagnosed with pancreatic ductal adenocarcinoma 2 years ago, and he experienced tumor recurrence and multiple metastases after pancreaticoduodenectomy and multi-line chemotherapies, including liver, peritoneum, and cervical lymph node metastases. Then, the patient was referred to our department for further treatment of metastatic PC, and he was enrolled in a clinical trial of claudin18.2-targeted CAR-T cell therapy. After lymphodepleting chemotherapy, the patient received claudin18.2-targeted CAR-T cell infusion at a dose of 1.2 x 106 cells/kg on November 21, 2022. During CAR-T cell therapy, the patient experienced grade 2 cytokine release syndrome (CRS) and gastric mucosa injury, which were controlled by tocilizumab and conventional symptomatic and supportive treatment. The patient achieved a complete response (CR) 1 month after claudin18.2-targeted CAR-T cell therapy, and remained in clinical remission for 8 months. Unfortunately, the patient experienced claudin18.2-negative relapse in July, 2023. Despite antigennegative relapse after claudin18.2-targeted CAR-T cell infusion, the patient achieved sustained remission for 8 months, which indicates that claudin18.2-targeted CAR-T cell therapy is an extremely effective therapeutic strategy for the treatment of advanced PC. [ABSTRACT FROM AUTHOR]

Objective: Postoperative data on Cushing's disease (CD) are equivocal in the literature. These discrepancies may be attributed to different series with different criteria for remission and variable follow-up durations. Additional data from experienced centers may address these discrepancies. In this study, we present the results obtained from 96 endoscopic transsphenoidal surgeries (ETSSs) for CD conducted in a well-experienced center. Methods: Pre- and postoperative data of 96 ETSS in 87 patients with CD were included. All cases were handled by the same neurosurgical team between 2014 and 2022. We obtained data on remission status 3-6 months postoperatively (medium-term) and during the latest follow-up (long-term). Additionally, magnetic resonance imaging (MRI) and pathology results were obtained for each case. Results: The mean follow-up duration was 39.5±3.2 months. Medium and long-term remission rates were 77% and 82%, respectively. When only first-time operations were considered, the medium- and long-term remission rates were 78% and 82%, respectively. The recurrence rate in this series was 2.5%. Patients who showed remission between 3-6 months had higher longterm remission rates than did those without initial remission. Tumors >2 cm and extended tumor invasion of the cavernous sinus (Knosp 4) were associated with lower postoperative remission rates. Conclusion: Adenoma size and the presence/absence of cavernous sinus invasion on preopera-tive MRI may predict long-term postoperative remission. A tumor size of 2 cm may be a supporting criterion for predicting remission in Knosp 4 tumors. Further studies with larger patient populations are necessary to support this finding. [ABSTRACT FROM AUTHOR]

Background: Gallbladder neuroendocrine carcinoma (GB-NEC) is an extremely rare cancer with a poor prognosis in the clinic. Although surgical resection remains the primary and preferred therapeutics, many patients are in a late stage and lose the opportunity for surgery. However, due to the extremely low morbidity, the specific treatment guidelines for GB-NEC have not been established. Case presentation: A 52-year-old woman was admitted to our hospital with the chief complaint of "almost 1 month after palliative surgery for metastatic gallbladder carcinoma." According to the results of pathological findings and imaging manifestations, the patient was diagnosed with GB-NEC with a clinical stage of pT3N1M1 (IVB). The patient then received tislelizumab plus EP chemotherapy (etoposide 100 mg + cisplatin 30 mg, d1-3) every 3 weeks for 8 cycles from 12 November, 2021, followed by maintenance therapy (tislelizumab alone) every 3 weeks until now. The tumor response was evaluated as complete remission since 13 February, 2023. As of the last followup, the patient remains alive, with no complaints of discomfort. Conclusions: Gallbladder NEC has no specific symptoms, and the diagnosis is based on pathological and immunohistochemical results. The therapeutic course and efficacy of the case in this study indicates that the application of PD-1 inhibitor might be a feasible therapeutic option for GB-NEC. However, this potential strategy needs validation by further clinical studies in the future. [ABSTRACT FROM AUTHOR]

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P  = .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value = 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization. [ABSTRACT FROM AUTHOR]

Abstract Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is considered for patients with high‐risk B‐cell lymphoma and relapsed or refractory disease. This study aimed to analyze the long‐term follow‐up data of patients who underwent allo‐HSCT in Taiwan. This was a retrospective observational study using data from the Taiwan Society of Blood and Marrow Transplantation database. A total of 105 patients who underwent allo‐HSCT because of high‐risk, relapsed, or refractory disease between 2010 and 2019 were included. Forty‐five percent of the patients previously underwent autologous stem cell transplantation (ASCT). The median follow‐up duration was 18.6 months. The probability of 3‐year progression‐free survival and overall survival (OS) was 34.5% and 37%, respectively. The probability of 1‐year non‐relapse mortality was 31.4%, and the major cause was infection (75.8%). The multivariable analysis showed that not in remission at the time of transplantation and the absence of graft‐versus‐host disease (GVHD) were factors associated with inferior OS. The probability of 3‐year OS in patients with diffuse large B‐cell lymphoma who underwent allo‐HSCT and allo‐HSCT after ASCT was 40.2% and 25.2%, respectively. Allo‐HSCT could be a salvage therapeutic option for relapsed or refractory B‐cell lymphoma. Complete remission at the time of allo‐HSCT and the presence of GVHD are independent variables for overall survival.

Örs Péter Horváth,1 Szabolcs Bellyei,2 Éva Pozsgai,3,4 András Vereczkei1 1Department of Surgery, University of Pécs Clinical Center, Pécs, 7624, Hungary; 2Department of Oncotherapy, University of Pécs Clinical Center, Pécs, 7624, Hungary; 3Department of Public Health, University of Pécs Medical School, Pécs, 7624, Hungary; 4Department of Primary Health Care, University of Pécs Medical School, Pécs, 7623, HungaryCorrespondence: Örs Péter Horváth, Department of Surgery, University of Pécs Clinical Center, Ifjúság Street 13, Pécs, 7624, Hungary, Tel +3672535806, Email horvath.ors.peter@pte.huAbstract: From a surgical point of view, the development of preoperative oncological treatment has had a profound effect on the surgical treatment trends of cancer as well as on the outcomes of cancer patients. Consequently, these changes have challenged formerly entrenched oncological surgical principles. In our short report, we aimed to summarize the main shifts regarding the surgical principles of cancer treatment due to the development of preoperative oncological therapy in recent years. As a result of successful preoperative treatment, surgeons may perform less radical surgeries, the required free resection margin has been narrowed down to a few millimeters in dimension and preoperative treatment is justified in both definitely resectable tumors and in oligometastatic tumors as well. For prognosis assessment, the post-preoperative oncological treatment stage is now considered decisive, rather than the pretreatment stage as previously thought. Other changes include the introduction of the watch and wait strategy and the reverse order of treatment of the primary tumor and metastasis. Observing the continuously improving outcomes of cancer patients and the developments in oncological treatment modalities, a further expansion of the indication of preoperative treatments is to be expected.Keywords: preoperative oncological therapy, neoadjuvant, downstaging, complete remission, surgical principles

Objective To investigate the 12-month renal remission in patients with lupus nephritis (LN) and the predictive factors. Methods The remission of patients with LN using biologic agents was analyzed by a prospective cohort study that included 57 patients with LN and positive urine protein, who were divided into hormone + immunosuppression group (n=39) and hormone + immunosuppression + biologics group (n=18) . Patients in hormone + immunosuppression group received standard therapy and those in hormone + immunosuppression + biologics group received standard therapy and belimumab. Long-term follow-up was assigned to collect and analyze data on renal response and clinical characteristics. Results Renal complete remission was achieved in 41 out of 57 patients (71.93%) and partial remission was achieved in 16 patients (28.07%) . Complete remission was achieved in 29 out of 39 patients in the hormone + immunosuppression group (mean time to complete remission was 7.846 months, 95%CI: 6.626-9.066 months) and in 12 out of 18 patients in the hormone + immunosuppression + biologics group (mean time to complete remission was 4.167 months, 95%CI: 3.461-4.872 months) .Conclusion Patients using both hormones, immune agents and biologics achieve complete remission more quickly than those using only hormones and immune agents. [ABSTRACT FROM AUTHOR]

Background Cancer-associated thrombosis although represents a significant disease worse prognosis, understanding its underlying pathophysiology remains obscure. Podoplanin and its platelet ligand C-type lectin receptor type-2 have been investigated in the past few years for their potential role as procoagulant substances as it has been shown in many studies that binding of podoplanin with platelet C-type lectin receptor type-2 results in enhancement of platelet aggregation and thrombotic insults. Aim In this study, serum podoplanin was measured in newly diagnosed acute myeloid leukemia (AML) patients and its relation to the incidence of thrombosis in these patients in addition to its relation to other clinical, laboratory, and prognostic outcomes. Patients and methods This study included 80 participants (60 newly diagnosed adult AML patients and 20 agematched and sex-matched healthy controls). Blood counts and flow cytometry using an acute leukemia panel were performed in addition to serum podoplanin, and cytogenetic studies including conventional karyotyping and fluorescence in-situ hybridization were performed to determine the risk group. The clinical status of the patients, particularly the incidence of thrombotic events in the following 6 months, as well as the D28 outcome and 6-month survival, were determined and reported. Results Serum podoplanin was highly expressed in AML patients compared with control samples, with a highly significant difference (P=0.001). There was a significant inverse relation between serum podoplanin level, hemoglobin level, and white blood cell count (P=0.006 and 0.036, respectively). Those with thrombotic events during the course of the disease did not show statistically significant results when compared with the control group with regard to serum podoplanin levels (P=0.546). Conclusion Serum podoplanin was much higher in AML patients than in the control group (P=0.000), and it was inversely related to platelet level (P=0.036) and total leukocyte count (P=0.006). However, there was no statistically significant link between podoplanin level and the incidence of thrombotic events (P=0.546). [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is considered for patients with high‐risk B‐cell lymphoma and relapsed or refractory disease. This study aimed to analyze the long‐term follow‐up data of patients who underwent allo‐HSCT in Taiwan. This was a retrospective observational study using data from the Taiwan Society of Blood and Marrow Transplantation database. A total of 105 patients who underwent allo‐HSCT because of high‐risk, relapsed, or refractory disease between 2010 and 2019 were included. Forty‐five percent of the patients previously underwent autologous stem cell transplantation (ASCT). The median follow‐up duration was 18.6 months. The probability of 3‐year progression‐free survival and overall survival (OS) was 34.5% and 37%, respectively. The probability of 1‐year non‐relapse mortality was 31.4%, and the major cause was infection (75.8%). The multivariable analysis showed that not in remission at the time of transplantation and the absence of graft‐versus‐host disease (GVHD) were factors associated with inferior OS. The probability of 3‐year OS in patients with diffuse large B‐cell lymphoma who underwent allo‐HSCT and allo‐HSCT after ASCT was 40.2% and 25.2%, respectively. Allo‐HSCT could be a salvage therapeutic option for relapsed or refractory B‐cell lymphoma. Complete remission at the time of allo‐HSCT and the presence of GVHD are independent variables for overall survival. [ABSTRACT FROM AUTHOR]

Introduction: For years, standard treatment for locally advanced rectal cancer (LARC) has included neoadjuvant chemoradiotherapy (CRT), followed by surgery and adjuvant chemotherapy. Although CRT has helped reduce local recurrence rates, it hasn't consistently improved overall survival. Recent trials have unveiled a different approach called total neoadjuvant treatment (TNT), involving presurgery radiotherapy followed by chemotherapy (CAPOX/FOLFOX). TNT shows promise with improved treatment response and lower distant metastasis rates without compromising local control. Consequently, many healthcare institutions have adopted TNT as their preferred neoadjuvant treatment. This study, conducted at a tertiary center, compares the real-world outcomes of both CRT and TNT protocols. Methods: In this retrospective study of 390 patients treated between 2015 and 2021, aged 18 or older with LARC and tumors within 12 cm of the anal verge, we compared treatment outcomes. We assessed factors like pathological complete remission (pCR), three-year event-free survival (EFS), and overall survival (OS) between the two treatment groups using the Chi-squared test. Results: Out of the 390 eligible patients, 256 underwent CRT, while 84 received TNT. Surgery was performed on 215 (84%) patients in the CRT group, compared to 55 (65.5%) in the TNT group. Notably, 33 (12.8%) achieved pCR in the CRT group, whereas 23 (27.7%) achieved pCR in the TNT group (P <.001). Regardless of whether surgery was performed or not, the TNT group exhibited lower recurrence rates (12.7% vs. 18.6% with surgery, 28.6% vs. 45% without surgery). The 3-year EFS rate was 80% in the CRT group and 90% in the TNT group (P = .05). Additionally, the 3-year OS rates favored the TNT group, standing at 96.4% compared to 84.4% in the CRT group (P = .005). Conclusion: Our findings indicate that patients who underwent TNT demonstrated a higher likelihood of achieving pCR and experienced lower recurrence rates compared to those in the CRT group. Additionally, the TNT group exhibited superior 3-year EFS and OS. It is important to note, however, that a longer follow-up period is required to further validate these results. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Key clinical message: Nivolumab has been clinically successful in prolonging the overall survival of patients with recurrent and metastatic head and neck cancer, complete remission is rare. Synergistic combinations of immunotherapy and conventional cancer treatments, such as radiotherapy or chemotherapy, are likely to be the most viable strategies for improving patient responses. Immune checkpoint inhibitors have revolutionized recurrent, metastatic oral cancer treatment; however complete remission in advanced stages is unusual. We present a case of complete remission of advanced oral squamous cell carcinoma for >4 years in a 64‐year‐old Japanese woman, that responded poorly to chemoradiotherapy but well to subsequent nivolumab treatment. [ABSTRACT FROM AUTHOR]

Background Although many human papillomavirus (HPV)–targeted therapeutic vaccines have been examined for efficacy in clinical trials, none have been translated into clinical use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and therapeutic efficacy of an HPV-16 E7-expressing lacticaseibacillus -based oral vaccine. Methods In a double-blind, placebo-controlled, randomized trial, a total of 165 patients with HPV-16–positive high-grade cervical intraepithelial neoplasia 2 and 3 were assigned to orally administered placebo or low, intermediate, or high doses of IGMKK16E7 (lacticaseibacillus paracasei expressing cell surface, full-length HPV-16 E7). In the 4 groups, IGMKK16E7 or placebo was administered orally at weeks 1, 2, 4, and 8 postenrollment. The primary outcomes included histopathological regression and IGMKK16E7 safety. Results In per-protocol analyses, histopathological regression to normal (complete response) occurred in 13 (31.7%) of 41 high-dose recipients and in 5 (12.5%) of 40 placebo recipients (rate difference = 19.2, 95% confidence interval [CI] = 0.5 to 37.8). In patients positive for HPV-16 only, the clinical response rate was 40.0% (12 of 30) in high-dose recipients and 11.5% (3 of 26) in recipients of placebo (rate difference = 28.5, 95% CI = 4.3 to 50.0). There was no difference in adverse events that occurred in the high-dose and placebo groups (P  = .83). The number of HPV-16 E7–specific interferon-γ producing cells within peripheral blood increased with level of response (stable disease, partial, and complete responses; P  = .004). The regression to normal (complete response) rates among recipients with high levels of immune response were increased in a dose-dependent manner. Conclusion This trial demonstrates safety of IGMKK16E7 and its efficacy against HPV-16–positive cervical intraepithelial neoplasia 2 and 3. IGMKK16E7 is the first oral immunotherapeutic vaccine to show antineoplastic effects. Trial registration jRCT2031190034. [ABSTRACT FROM AUTHOR]

The present study examined the therapeutic effects of preoperative neoadjuvant chemoradiation therapy (NACRT) and predictive factors for complete clinical remission, compared the prognosis and costs of abdominoperineal resection (APR) and the "watch and wait" method (WW), and evaluated the usefulness of WW. In our department, patients with stage II–III lower rectal cancer requiring APR receive NACRT. NACRT was performed as a preoperative treatment (52 Gy + S-1: 80–120 mg/day × 25 days). Eight weeks after the completion of NACRT, rectal examination, endoscopic, computed tomography, and magnetic resonance imaging findings were evaluated to assess its therapeutic effects. APR was indicated for patients in whom endoscopic findings suggested a residual tumor in which a deep ulcer or marginal swelling remained or lymph node metastasis. However, WW was selected for patients who refused APR after informed consent was obtained. In the APR and WW groups, 5- and 20-year treatment costs after CRT were calculated using the Medical Fee Points of Japan in 2020. No significant differences were observed in 3-year disease-free survival rates for either parameter between the two groups. Regarding expenses, treatment costs were lower in the WW group than in the APR group. Organ preservation using active surveillance with CRT for rectal cancer requiring APR is feasible with the achievement of endoluminal complete remission. [ABSTRACT FROM AUTHOR]

Programmed cell death protein 1 (PD-1) inhibition plays a central role in the current treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). Some patients achieve a durable response, and even complete remission (CR) is possible, though it occurs rarely. In cases of durable CR, there are no guidelines regarding a possible discontinuation of immunotherapy. Since clinical experience on this issue is limited, the present study reported on a case of a durable CR following discontinuation of PD-1 inhibition in R/M-HNSCC and additionally presented an overview on the current literature. The present study reported on a case of CR of recurrent oropharyngeal cancer after four cycles of PD-1 monotherapy with Nivolumab. The therapy was discontinued after overall 46 cycles. Even after 3 more years of follow-up, there was no sign of tumor recurrence. Overall, according to reports from the literature, CR seems to be an indicator for durable disease control after therapy discontinuation. Since data on therapy termination is rare, decisions about when to stop successful immunotherapy in R/M-HNSCC have to be made individually for each patient. [ABSTRACT FROM AUTHOR]

BackgroundMycosis fungoides (MF) is a cutaneous lymphoma; most patients present with early, skin-limited disease and are managed by dermatologists.ObjectiveThe purpose of this study was to systematically review and assess the evidence on topical treatments for early-stage (IA, IB, IIA) MF.MethodsWe performed a literature search via MEDLINE, Embase, Web of Science, and Cochrane databases. Grading Recommendations Assessment, Development and Evaluation (GRADE) criteria were used to assess the certainty of the data.ResultsTwo searches yielded 1252 references; 26 met the inclusion criteria and included literature on nitrogen mustard, retinoids, corticosteroids, carmustine, fluorouracil, methotrexate-laurocapram, hexadecylphosphocholine, peldesine, ingenol mebutate, topical methotrexate with oxygen flow-assisted LP3 carrier, and resiquimod. Most studies were single intervention, observational series. Nitrogen mustard, with the most published reports, was effective with 12%-82% early-stage MF patients (total n > 1000) achieving complete remission (CR) (low certainty evidence). Clinical CR was achieved among 10%-60% treated with topical retinoids (low certainty evidence). Two moderate-sized retrospective case series on topical steroids had 18%-63% CR (low certainty evidence). Only single studies were available for the other therapies.ConclusionsFor most outcomes of interest, the GRADE certainty for topical therapies for early-stage MF was low. Further randomized controlled trials and inclusion of quality of life indicators are needed.

Abstract Background The hypomethylating agent decitabine is the standard therapy for intermediate or high risk myelodysplastic syndrome (MDS). Methods In this trial, 191 adult patients with intermediate/high risk MDS (IPSS score ≥ 0.5) randomly received decitabine using a standard regimen (20 mg/m2/day for 5 consecutive days; n = 94) or an extended regimen with lower daily dose (12 mg/m2/day for 8 consecutive days; n = 97) every 4 weeks, for a total of 4 cycles. Results The median follow‐up was 14 months (range 2–36). The primary end point of overall response rate in the intent‐to‐treat analysis was 41.5% and 38.1% in the standard and extended dosing arms, respectively (p = 0.660). Complete remission and marrow complete remission also did not differ between the two arms. Cytopenia was the most frequent adverse event (76.4%). The median duration of neutropenia per cycle did not differ between the two arms during the first two cycles, but significantly shorter in the extended dosing arm in the third cycle (8.5 vs. 15.5 days, p = 0.049) and in the fourth cycle (8 vs. 14 days, p = 0.294). Conclusion The 5‐day 20‐mg/m2/day and 8‐day 12‐mg/m2/day decitabine regimens have similar efficacy and safety in patients with intermediate or high risk MDS.

Abstract Background The prognosis for recurrence cases of hormone receptor-positive HER2-negative breast cancer remains poor, and treatment strategies that emphasize quality of life have often been chosen, with few physicians aiming for a cure. Our objective is to assess the validity of such current treatment strategies. Case presentation A 74-year-old Asian woman with multiple lung and liver metastases after local recurrence of breast cancer was treated with two different cyclin-dependent kinases 4/6 inhibitors sequentially in combination with endocrine therapy. Flow cytometric analysis of the patient’s peripheral blood mononuclear cells was also performed to evaluate the host’s immune status. Complete remission was achieved without cytotoxic agents and the patient remains disease free to this day, 6 years after the initial relapse. Additionally, no increase in the population of the immunosenescent T cells with a phenotype of CD8+CD28− was observed in the patient’s peripheral blood mononuclear cells, suggesting that the immune system was well maintained. Conclusions We present this case study to develop new treatment strategies for recurrent breast cancer that is not only bound to misinterpretations of the Hortobagyi algorithm, but also aim for a cure with noncytotoxic agents to maintain the host’s immune system and early detection of recurrence.

Background: Cell-free DNA (cfDNA) is a promising biomarker for disease prediction in many cancers, including acute leukemia (acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL]). This study investigated the role of cfDNA in predicting relapse or unfavorable outcomes in acute leukemia patients upon initial diagnosis.Methods: Paired peripheral blood samples of 25 patients with ALL and AML were compared at baseline and induction/follow-up and clinically correlated with clinicopathological and outcome variables according to the risk category. cfDNA was isolated using commercial cfDNA extraction kits. The probability of poor outcomes in high-risk groups and a cut-off value for risk stratification minimal residual disease (MRD) positivity and outcome prediction were derived.Results: Twenty-five patients diagnosed with AML and ALL were risk-stratified based on NCI risk stratification, and of these 25 patients, 4 patients were of standard risk (SR) and 1 patient was of intermediate risk (IR), while a majority of patients (80%) were of high risk (HR). Of these, four HR patients passed away. The ratio of cfDNA reduction at baseline and the end of induction was a strong predictor of poor outcomes in high-risk patients, regardless of the MRD status. A cfDNA ratio score of 2.6 or higher at diagnosis/remission predicted poor outcomes, with higher accuracy than conventional MRD detection by flow cytometry.Conclusion: A higher cfDNA ratio at diagnosis/remission or at baseline predicts poor outcomes in acute leukemia patients. This pilot study suggests that cfDNA ratio scoring may be a useful tool for predicting prognosis in acute leukemia patients, regardless of the MRD status.

Key clinical message Nivolumab has been clinically successful in prolonging the overall survival of patients with recurrent and metastatic head and neck cancer, complete remission is rare. Synergistic combinations of immunotherapy and conventional cancer treatments, such as radiotherapy or chemotherapy, are likely to be the most viable strategies for improving patient responses. Abstract Immune checkpoint inhibitors have revolutionized recurrent, metastatic oral cancer treatment; however complete remission in advanced stages is unusual. We present a case of complete remission of advanced oral squamous cell carcinoma for >4 years in a 64‐year‐old Japanese woman, that responded poorly to chemoradiotherapy but well to subsequent nivolumab treatment.

AbstractBackground 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)