Partial Remission Research Articles

CLAG±DAC regimen in the treatment of refractory/relapsed acute myeloid leukemia

Objective: To investigate the efficacy and prognosis of CLAG±DAC (Clofarabine, Cytarabine, G-CSF±Decitabine) chemotherapy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) . Methods: Continuous cases of R/R AML treated with the CLAG+DAC protocol or CLAG alone at the First Affiliated Hospital of Soochow University from January 2017 to December 2021 were retrospectively analyzed. The baseline characteristics, individual treatment regimen, treatment effect, disease progression, and survival status of patients were recorded. The factors influencing the efficacy of the CLAG±DAC chemotherapy regimens were analyzed, and the overall survival (OS) time after reinduction was calculated using the Kaplan-Meier method. Results: This study included a total of 53 patients, with 33 male patients and an average age of 40.6 years. Thirty-three patients achieved complete remission (CR+CRi) of the disease after the CLAG±DAC chemotherapy regimen and six patients achieved partial remission (PR), while 14 did not. Thirty-two patients eventually underwent hematopoietic stem cell transplantation, and the median OS of the patients was 55.9 months until follow-up. Patients with disease remission after the application of the CLAG±DAC chemotherapy had a significantly longer survival time than those without remission (P<0.001). The results of the multifactorial analysis have revealed that combined DAC (OR=4.60, 95% CI 1.14-23.5, P=0.04) and DNMT3A mutation (OR=0.14, 95% CI 0.01-0.89, P=0.05) were the factors influencing the efficacy of the CLAG±DAC chemotherapy regimen. The remission rate was relatively higher in patients with R/R AML combined with FLT3-ITD mutation by applying the DAC+CLAG regimen (OR=10.84, 95%CI 1.48-288.50, P=0.04) . Conclusion: The CLAG±DAC regimen is considered effective in patients with R/R AML, whereas decitabine combined with the CLAG regimen is more suitable for patients with R/R AML combined with FLT3-ITD mutation.

Rotation or change of biotherapy after TNF blocker treatment failure for axial spondyloarthritis: the ROC-SpA study, a randomised controlled study protocol

IntroductionAxial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammatory low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first treatment in axSpA. In case of inadequate...

Plasma proteomics in children with new-onset type 1 diabetes identifies new potential biomarkers of partial remission

Partial remission (PR) occurs in only half of people with new-onset type 1 diabetes (T1D) and corresponds to a transient period characterized by low daily insulin needs, low glycemic fluctuations and increased endogenous insulin secretion. While identification of people with newly-onset T1D and significant residual beta-cell function may foster patient-specific interventions, reliable predictive biomarkers of PR occurrence currently lack. We analyzed the plasma of children with new-onset T1D to identify biomarkers present at diagnosis that predicted PR at 3 months post-diagnosis. We first performed an extensive shotgun proteomic analysis using Liquid Chromatography-Tandem-Mass-Spectrometry (LCMS/MS) on the plasma of 16 children with new-onset T1D and quantified 98 proteins significantly correlating with Insulin-Dose Adjusted glycated hemoglobin A1c score (IDAA1C). We next applied a series of both qualitative and statistical filters and selected protein candidates that were associated to pathophysiological mechanisms related to T1D. Finally, we translationally verified several of the candidates using single-shot targeted proteomic (PRM method) on raw plasma. Taken together, we identified plasma biomarkers present at diagnosis that may predict the occurrence of PR in a single mass-spectrometry run. We believe that the identification of new predictive biomarkers of PR and β-cell function is key to stratify people with new-onset T1D for β-cell preservation therapies.

Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91–87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11–22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0–2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

Adjunctive use of mindfulness-based mobile application in depression: randomized controlled study.

Mindfulness-based interventions (MBI) are effective in relapse prevention in Major Depressive Disorder (MDD). Internet-based interventions have been demonstrated to be effective in the treatment of MDD. Consequently, the integration of MBI through mobile applications emerges as a promising supplementary intervention for MDD, contributing to the augmentation of mental health services, particularly within ambulatory care contexts. The current randomized controlled study is designed to evaluate the efficacy of adjunctive MBI delivered via a mobile app in mitigating symptom severity and stress levels. This assessment involves a comparison with standard treatment practices in an ambulatory setting among individuals diagnosed with MDD. A total of 83 patients diagnosed with MDD (depressive episode, recurrent depression or depressive phase of bipolar disorder) were randomly allocated to the intervention (41 patients) or control condition (42 patients). The intervention consisted of the daily use of the mindfulness mobile application "Headspace" for thirty days. The control condition was treatment as usual (TAU) only. The symptom severity has been assessed by the Beck Depression Inventory (BDI-II) as well as the Hamilton Depression Rating Scale (HDRS-17). Blood pressure and resting heart rate have been assessed as secondary outcome. Upon hospital discharge, the mean scores on the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS) signaled partial remission of MDD in both treatment arms. In both groups, a subsequent decrease in both self-reported and expert-rated scores was evident after a 30-day period. However, the decrease in depression severity as measured by HDRS was significantly higher in the MBI group compared to the control group after 30days. For secondary outcomes, systolic blood pressure was lower in the intervention group compared to control group. The total drop-out rate was 29%. Short term mindfulness intervention via mobile application (30days) can be beneficial as adjunctive therapy to treatment as usual in patients with MDD.

Anaphylactic Shock Caused by Eating Buckwheat.

Background: Urticaria is a common disease with a marked influence on quality of life. The key cell involved is the mast cell, which can be activated by a vast variety of stimuli, and the major mediator is histamine. Allergic urticaria is a disorder with a large variety of causes: food, drugs, insect venom, skin contact with allergens, and physical exercise. Buckwheat consumption has increased in European countries and the USA because it is gluten-free. It can trigger anaphylactic shock if ingested, inhaled, or handled with the hands. Five common buckwheat allergens named Fag e1 to 5 (Fag e1, 2, and 3 are considered the major allergens) and two tartary buckwheat allergens named Fag t1 and Fag t2 have been described. Method: We present the case of a patient who experienced two anaphylactic shocks and in whom the etiological factor was buckwheat. The patient presented to the Allergology department for the evaluation of two episodes of severe allergic reactions that required emergency therapy, episodes that involved the loss of consciousness and were of major severity. At each anaphylactic shock, an ambulance was requested, and emergency therapy was administered, leading to the patient's recovery within a few hours. Diagnosis: Since each episode occurred a few minutes after eating, the diagnosis was established based on a detailed anamnesis and prick skin tests, followed by specific IgE dosages. Other foods consumed by the patient, assessed by prick skin testing and specific IgE dosages of suspected foods, were excluded as the etiological cause. Increased levels of buckwheat-specific immunoglobulin E were highlighted, thus identifying the etiological agent. The treatment of anaphylactic shock was performed urgently by the ambulance crew with adrenaline, infusion solutions, cortisone preparations, and antihistamines. Result: Following the treatment that was initiated, there was a partial remission of the lesions after a few hours. Conclusions: Buckwheat allergy is rare, but it produces symptoms that affect the skin, gastrointestinal tract, and respiratory tract, as well as anaphylaxis. In a professional environment, it can trigger allergic rhinitis, asthma, and hives. Although buckwheat allergens have been described, their clinical relevance has only been studied in a small number cases. In current practice, the only commercially available allergen is Beech e2 per the ImmunoCAP ISAC microarray. Diagnosis can be difficult in clinical practice. This reported case suggests the need for a thorough anamnesis, since buckwheat is consumed as a hidden allergen, and in Europe, it is not necessary to label foods containing this allergen.

Association between partial remission phase in type 1 diabetes and vitamin D receptor Fok1 rs2228570 polymorphism.

The aim of the current study was to assess the natural course of partial remission (PR) phase of type 1 diabetes (T1D) and to highlight the putative association between vitamin D receptor (VDR) (Fok1) gene polymorphism and PR phase. Ninety participants with newly diagnosed T1D were followed up for a total of 12months. The VDR (Fok1) rs2228570 gene polymorphism was genotyped using allelic discrimination (AD) assay. Fifty-four patients (60 %) reached PR with an average duration of 5.63±2.9months. Among remitters, the frequency of CC "FF" genotype and allelic frequency of C "F" were significantly higher (p<0.001). Furthermore, participants expressing "CC" genotype had earlier onset of PR and spent a significantly longer duration in remission (p<0.001). Younger age (p<0.001; OR 41.6; CI 12.12-142.99), absence of DKA (p<0.001; OR 16, CI 4.36-50.74), higher C-peptide levels (p<0.001; OR 19.55; CI 6.52-58.63), and presence of CC "FF" genotype of VDR (p<0.001; OR 6.74; CI 2.41-18.86) best predicted the overall occurrence of PR. Younger age, less extent of metabolic derangements, and expression of a CC "FF" genotype were found to influence the occurrence of PR. Data from the current study showed that the "C" allele could have a protective role on preserving residual β-cell mass and could predict both onset and duration of PR among newly diagnosed T1D. These findings support the growing concept of future tailored precision medicine.

Immunosuppression-Based Lymphoproliferative Disease Features and Parameters Affecting Survival

Aim: Lymphoid cell malignancies originate from the immune cells at various stages of differentiation, ranging from the slowest progressing ones to the most aggressive types. The immune deficiency-associated lymphomas are less frequently seen with worse prognoses, poor treatment responses, and high mortality rates than the primary lymphomas. In this study, we aim to evaluate the clinical and laboratory findings and to determine the survival rates, treatment responses, and the factors that may influence the mortality and survival rates in patients with immunodeficiency-associated lymphomas. Methods: The study included 15 patients with immunodeficiency-associated lymphomas and 49 patients with newly diagnosed primary lymphomas between January 2013 and January 2023. Patient characteristics, treatments, and mortality rates were retrospectively analyzed using data charts. Results: The remission and partial remission rates after the treatment were significantly lower in the patients with immunodeficiency-associated lymphomas [p=0.025; OR=5.6 (1.4-22, 95%CI)]. The IPI values of the primary lymphoma patients were significantly lower. Upon evaluating all patients in both groups collectively, a discernible trend indicated a deterioration in treatment responses correlating with escalating International Prognostic Index (IPI) values (p &lt; 0.001). The levels of β-2 microglobulin were higher in the deceased patients (3.4±1.8mg/l vs 5.2±1.8mg/l; p

Abstract P209: The novel angiotensin Alamandine-(1-5) is increased in plasma of pediatric patients with primary nephrotic syndrome

Background and Aim: The Renin Angiotensin System (RAS) has an important role in the pathophysiology of primary nephrotic syndrome (NS). It was previously found that urinary levels of angiotensin converting enzyme 2 (ACE2) are reduced in patients with NS in comparison to health controls. The aim of this study was to measure the novel angiotensin peptide, Alamandine-(1-5), in plasma samples of patients with primary NS and to compare with sex and age-matched controls. Methods: Blood samples of pediatric patients with primary NS (n=11) and of sex and age-matched health controls (n=11) were collected in sterile tubes with 7.5% (w/v) EDTA. After plasma separation and purification by solid phase extraction, the circulating levels of Alamandine and of Alamandine-(1-5) were measured by Mass Spectrometry using multiple reaction monitoring on an ACQUITY I-Class UPLC system coupled to electrospray ionization (ESI) tandem mass spectrometry (LC-ESI-MS/MS Xevo TQ-S). Data were compared between patients and controls and associated with laboratory findings. Continuous variables were presented as mean ± standard error of the mean. Results: A total of 11 patients (7 males) with NS with mean age of 10.65±3.66 were compared to 11 controls (6 males) and with 10.86±4.35 years. In terms of disease response, 5 patients were in partial remission, 5 patients in total remission and only 1 patient was in disease relapse. All patients have normal renal function. Plasma levels of Alamandine-(1-5) were significantly higher in patients when compared to controls (28.03±7.54 vs. 10.68±3.02 pg.mL-1 in controls). Despite a mild decrease in patients, plasma levels of Alamandine did not differ between groups (19.54±6.33 vs 26.09±6.12 pg.mL-1 in controls). No correlations were found between RAS molecules and proteinuria and with the medications in use. However, Alamandine-(1-5) negatively correlated with plasma levels of albumin (r= -0.695; p=0.038). In addition, Alamandine negatively correlated with total cholesterol (r=-0.700; p = 0.036), LDL (r=-0.800; p=0.004), and HDL (r = -0.762; p = 0.038). Conclusion: The novel RAS peptide Alamandine-(1-5) is significantly increased in primary NS and inversely correlated with plasma albumin levels. These findings suggest a potential role of Alamandine-(1-5) in NS

Pilot Trial of Hydroxychloroquine as Add-On Therapy in Patients With Membranous Nephropathy

BackgroundKidney Disease Improving Global Outcomes guidelines indicate that glucocorticoids and immunosuppressants comprise the first therapeutic regimens after 4–6 months of treatment for high-risk primary membranous nephropathy (PMN). However, some patients cannot achieve complete or partial remission at 6 months. This study aimed to evaluate the efficacy of traditional immunotherapy combined with hydroxychloroquine (HCQ), a well-known immune regulator, in patients with PMN. MethodsThis was a single-center, open-label, prospective study. We recruited 72 patients with nephrotic syndrome and PMN proven by renal biopsy from May 2020 to June 2024. We compared changes in proteinuria, serum albumin levels, estimated glomerular filtration rate, and relapse rate at 3, 6, 9, and 12 months follow up in 41 patients who received glucocorticoid and immunosuppressant, and in 31 who received HCQ plus standard-of-care. ResultsBaseline characteristics showed no statistical significance between the two groups. However, the HCQ group showed significantly reduced proteinuria compared to standard-of-care group. A reduced proteinuria was seen at 6 months [1.2 (0.4, 2.2) vs. 2.2 (1.0, 3.8) g/day, P = 0.029] and the relapse rate with 12 months follow up was also significantly decreased in HCQ group compared to standard-of-care group (3.7% vs. 23.3%, P = 0.033). ConclusionsHCQ may serve as an effective add-on therapy for primary membranous nephropathy.

Beyond the Descriptive: A Comprehensive, Multidomain Validation of Symptom Trajectories for Individuals at Clinical High Risk for Psychosis

BackgroundAlthough the clinical high risk for psychosis (CHR-P) criteria are widely used to ascertain individuals at heightened risk for imminent onset of psychosis, it remains controversial whether CHR-P status defines a diagnostic construct in its own right. In a previous study, CHR-P nonconverters were observed to follow 3 distinct trajectories in symptoms and functioning: remission, partial remission, and maintenance of symptoms and functional impairments at subthreshold levels of intensity. MethodsHere, we utilized the NAPLS3 (North American Prodrome Longitudinal Study phase 3) sample (N = 806) to determine whether 1) the same trajectory groups can be detected when assessing symptoms at 2-month intervals over an 8-month period and 2) the resulting trajectory groups differ from each other and from healthy control participants and converting CHR-P cases in terms of risk factors, comorbidities, and functional outcomes. ResultsThree distinctive subgroups within the CHR nonconverters were identified, largely paralleling those observed previously. Importantly, these extracted groups, together with non-CHR control participants and CHR converters, differed from each other significantly on putative etiological risk factors (e.g., predicted risk scores, physiological and self-report measures of stress), affective comorbidities, and functional outcomes, thus providing converging evidence supporting the validity of the identified trajectory groups. ConclusionsThis pattern, together with the fact that even the subgroup of CHR-P nonconverters who showed a remission trajectory deviated from healthy control participants, supports treating the CHR-P syndrome not only as a status that denotes risk for onset of full psychosis but also as a marker of ongoing distress for a population that is in need of interventions.

212. CLINICAL RESULTS OF PHOTODYNAMIC THERAPY FOR ESOPHAGEAL CANCER PATIENTS WITH INOPERABLE CONDITION

Abstract Background Although surgical resection is the best way for curing cancer, there has been a certain portion of patients who could not undergo surgery because of various reasons. We experienced 10 cases of photodynamic therapy for esophageal cancer patients (Including one case of carcinoma in-situ) with inoperable conditions, and investigated the feasibility and safety of photodynamic therapy (PDT). Methods Medical records of patients of esophageal cancers who received photodynamic therapies between 2005 and 2022 in our institute were reviewed retrospectively. Survival, complication rates and treatment results were evaluated. Results Average age at the time of treatment was 72.4 (±6.47, ranging 64 to 86) and average follow-up periods were 25.0 (±27.7, ranging 3.8 to 89.8). The average Charlson Comorbidity Index (CCI) were 7.3 (±2.29, ranging 4 to 10). During the follow-up periods, 5 patients died, and only one death was related with the esophageal cancer progression. There was one case of skin reaction and no other complications were appeared. There were no complication related deaths. Complete remission of esophageal cancer showed in 7 patients (70.0%) and partial remission showed in 3 patients (30.0%). Two patients with partial remission showed loco-recurrence. One patient with complete remission had to undergo surgery because of preexisting esophageal stenosis. Conclusion Photodynamic therapy could be an option of palliative therapy for advanced esophageal cancer with reasonable complication rates. Therapeutic application could be considered in early esophageal cancer, especially for patients with poor general condition or refusal of surgery. It was still in debates whether it could substitute the surgical role in early esophageal cancers.

Update on Palmar Fasciitis and Polyarthritis Syndrome: A systematic review

ObjectivesThis systematic review aims to (1) summarize the clinical, laboratory, and imaging characteristics of Palmar Fasciitis and Polyarthritis Syndrome (PFPAS) patients and (2) evaluate the effectiveness of different treatments. MethodsWe conducted a systematic search of three electronic databases (Scopus, Embase, and PubMed) from inception to December 31, 2023. We presented demographic and clinical features, along with laboratory factors and imaging examinations of PFPAS patients. Additionally, we outline main treatments and evaluate therapeutic effectiveness. ResultsA total of 121 patients were included in the analysis, with a mean onset age of 61.4 years. Swelling or thickening (49.6%, n=60/121) and pain (41.3%, n=50/121) were characteristic musculoskeletal symptoms of the hands. The median time between onset of PFPAS symptoms and detection of malignancy was 4 months, with a median survival of 13.0 months (range=2 to 69). The abnormal rate of ultrasound, magnetic resonance imaging, and bone scan of the musculoskeletal system was more than 80%. Effective therapeutic responses were observed in 66.0% (n=33/50) of cases treated with chemotherapies and 79.2% (n=19/24) with operations. Two patients who received biologics achieved partial remission. ConclusionPFPAS is a rare paraneoplastic condition, and early recognition of its distinctive symptoms may lead to the detection of underlying malignancy and timely treatments, potentially saving lives.

Several factors that predict the outcome of large B-cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T-cell therapy can be identified before cell administration.

The aim of this study was to analyse the outcomes of patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CAR-Tx), with a focus on outcomes after CAR T-cell failure, and to define the risk factors for rapid progression and further treatment. We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd-line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression-free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty-three patients (59%) were refractory or relapsed after CAR-Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow-up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR-Tx. Risk factors for not receiving further therapy after CAR-Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS-2 (from R/P after CAR-Tx) was 6.7 months (6-month 57.9%) for treated patients and 0.4 months (6-month 4.2%) for untreated patients (p < 0.001). The median PFS-2 (from R/P after CAR-Tx) was 3.2 months (6-month 28.5%) for treated patients. The risk factors for a shorter PFS-2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS-2 for treated patients. Our findings allow better stratification of CAR-Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement).

Performance of cut-offs of the ASAS Health Index to discriminate between treatment groups in patients with axial spondyloarthritis in the TICOSPA trial

ObjectiveTo test trial and longitudinal known group discrimination of thresholds of meaning for improvement and health states of the ASAS Health Index (ASAS HI) in patients with active axSpA treated in a randomized study. MethodsData from baseline and week 48 from the tight-controlled, treat-to-target trial TICOSPA study were used. The performance of different thresholds to assess change or health states of the ASAS HI were evaluated between arms and against changes in patients’ relevant outcomes and various external responder criteria. Analyses were performed by comparing the mean values t-tests or proportion of responders of continuous and dichotomous external criteria respectively. Trial discrimination of the ASAS HI thresholds were assessed by odds ratios and Phi coefficient in a large number of potential ASAS HI thresholds. Differences in health states in relevant external outcomes between ASAS HI responders and non-responders was assessed by comparing the best performing improvement and state thresholds by using t-tests and chi-square, as appropriate. Missing data on outcomes was handled by non-responder imputation (NRI). ResultsAll 160 patients had available ASAS HI data. Trial discrimination was larger for absolute ASAS HI change of ≥2.0, ≥2.5, and ≥3.0 points followed by ASAS HI 20 % improvement. Odds ratio ranged between 1.27 and 1.75 for absolute and between 1.0 and 1.64 for relative improvement outcomes. Longitudinal discrimination of ASAS HI improvement ≥30 % or ≥ 3.0 points had a larger reduction in patient global and disease activity and reached more often remission compared to patients with no significant improvement in global functioning. Patients who achieved ASAS HI ≤ 5.0 compared with patients who did not achieve such states were more likely to have ASAS partial remission, ASDAS inactive disease or ASDAS low activity at week 48. ConclusionsThe data-driven thresholds of the ASAS HI identified in a longitudinal observational setting perform well in the context of a randomized trial.

Comparison of obinutuzumab and rituximab for treating primary membranous nephropathy.

This study compared the effectiveness and safety profiles of obinutuzumab and rituximab in the treatment of patients with primary membranous nephropathy. Patients with primary membranous nephropathy who had urine protein ≥ 3.5 g/24 hours and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 despite six months of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker and treatment with obinutuzumab or rituximab were included and matched by propensity score (ratio: 1:2) based on age, sex, urine protein, eGFR, and titers of Anti-Phospholipase A2 receptor (PLA2R) antibody. The primary outcome was defined as a combination of partial or complete remission at 12 months. Logistic regression models, Kaplan Meier curves, and absolute risk differences were employed to compare the therapeutic effectiveness and safety profiles of obinutuzumab and rituximab. Sixty-three patients with primary membranous nephropathy were included in the study, with 21 patients receiving obinutuzumab and 42 patients receiving rituximab. At 12 months, the primary outcome was achieved in 20 of 21 patients in the obinutuzumab group and 28 of 42 patients in the rituximab group (obinutuzumab vs. rituximab: 95% vs. 67%; odds ratio (OR): 10.00, 95% confidence intervals (CI):1.21-82.35, P=0.03). Moreover, patients in the obinutuzumab group acquired more complete remission (obinutuzumab vs. rituximab: 38% vs. 14%; OR: 3.69, 95% CI:1.08-12.68, P=0.04). In PLA2R-associated primary membranous nephropathy subgroup analyses, patients in obinutuzumab group sustained lower CD19 B cell counts (CD19 B cell counts: median (IQR) 0 (0-6) cells/ul vs. 20 (3-58) cells/ul, P=0.002) and were more prone to achieve immunological remission (defined as PLA2R antibody <2 RU/ml) at six months [obinutuzumab vs. rituximab: 92% (12 out of 13) vs. 64% (16 out of 25), P=0.06] than rituximab. Both treatment regimens were well tolerated. Our study demonstrated that obinutuzumab is associated with higher odds of clinical remission compared to rituximab at 12 months which may be due to higher immunological remission at six months with a similar safety profile in patients with primary membranous nephropathy.

Clinical Outcomes in Pediatric Patients With Type 1 Diabetes With Early Versus Late Diagnosis: Analysis From the DPV Registry.

This study was conducted to evaluate the effects of early clinical diagnosis of type 1 diabetes by comparison of clinical parameters at diagnosis and during follow-up in patients with pediatric type 1 diabetes with early, intermediate, and late diagnosis. In a population-based analysis, data on 14,292 pediatric patients with type 1 diabetes diagnosed between 2015 and 2019 were retrieved from the Diabetes Prospective Documentation (DPV) registry in March 2023. Patients were divided into four groups: one with diabetic ketoacidosis (DKA) at diagnosis and three with early, intermediate, or late diagnosis based on age-dependent HbA1c terciles. Laboratory-measured HbA1c values and those estimated from continuous glucose monitoring were aggregated as a combined glucose indicator (CGI). Insulin-dose adjusted CGI values <9% were defined as partial remission. At diagnosis, patients had a median age of 9.8 years (IQR = 6.8; 13.0). Three years later, patients with early diagnosis had lower CGI than patients with late diagnosis or DKA (mean [95% CI] 7.46% [7.40; 7.53] vs. 7.81% [7.75; 7.87] or 7.74% [7.68; 7.79], respectively; each P < 0.001). More patients experienced partial remission (12.6% [11.0; 14.4] vs. 9.1% [7.7; 10.7] or 8.6% [7.3; 10.0]; each P < 0.001), and 11.7% [10.2; 13.5] of patients with intermediate diagnosis were in partial remission. Early clinical diagnosis of type 1 diabetes may be beneficial for metabolic control and remission after 3 years of follow-up. Patients diagnosed early may represent a distinct group with better resources or with a different disease biology and slower β-cell destruction, which needs further evaluation.

Safety and Tolerability of ADR-001 Therapy for Immunoglobulin A Nephropathy.

Immunoglobulin A nephropathy often requires kidney replacement therapy because of its refractoriness and because corticosteroids pose infection risks. However, mesenchymal stem cells offer clinical benefits because of their regenerative and immunomodulatory properties. This prospective clinical trial assessed the safety and tolerability of adipose-derived mesenchymal stem cell therapy and evaluated its therapeutic efficacy. This phase 1 study included adult patients with refractory immunoglobulin A nephropathy that was difficult to treat with traditional therapies. Adipose-derived mesenchymal stem cell therapy comprising one intravenous dose of 1 × 108 cells was administered to three to six patients in cohort 1. The same intravenous dose was administered twice with a 2-week interval to six patients in cohort 2. Heparin was administered simultaneously. This study continued for 52 weeks, and the primary endpoints were safety and tolerability during the 6-week period after treatment administration. Secondary endpoints included adverse events and efficacy measures such as clinical remission, partial remission, urine protein remission, hematuria remission, time to remission, changes in the urine protein and hematuria levels, and changes in the estimated glomerular filtration rate. The three patients in cohort 1 and six patients in cohort 2 who received adipose-derived mesenchymal stem cell therapy achieved the primary endpoints. No severe adverse clinical events were observed. Therefore, the safety and tolerability of adipose-derived mesenchymal stem cells were confirmed. Improvements such as significantly decreased kidney damage markers and urinary protein levels were observed immediately after adipose-derived mesenchymal stem cell administration. The safety and tolerability of adipose-derived mesenchymal stem cells are acceptable for patients with immunoglobulin A nephropathy. This trial was registered with the Japan Registry of Clinical Trials (jRCT2043200002; registration date: April 14, 2020) and ClinicalTrials.gov (NCT04342325; registration date: April 13, 2020).

Multidisciplinary team discussion based on etiological treatment improves refractory chronic cough outcomes

BackgroundRefractory chronic cough (RCC) causes significant impairments in the life quality of patients. Further research into the identification of etiologies and development of the treatment schedules for RCC is needed. Patients and methodsWe established an multidisciplinary team (MDT) clinic, by integrating respiratory medicine, otorhinolaryngology, and gastroenterology departments, to investigate cough etiologies and the effectiveness of treatment. The therapeutic effect was assessed quantitatively using the Cough Visual Analog Scales (VAS), Leicester Cough Questionnaire (LCQ), and Reflux Symptoms Index (RSI) scores. ResultsIn total, 213 patients attending the MDT outpatient clinic were examined, and 115 patients with RCC were included for analysis. The RCC diagnosis rate among the outpatient was 88.7%. Common causes of RCC included gastroesophageal reflux cough (63.5%), upper airway cough syndrome (UACS) (43.5%), and cough variant asthma (CVA) (14.8%). After an average treatment period of 2.17 ± 1.06 weeks (wk), 73.9% of the patients had partial cough remission, and 6.1% had complete cough remission. The cough VAS score before and after treatment was 6.11 ± 2.02 vs. 3.66 ± 2.22 (P < 0.05), respectively; LCQ total score before and after treatment was 10.24 ± 3.11 vs. 13.16 ± 3.59 (P < 0.05), respectively; and RSI score before and after treatment was 15.82 ± 7.01 vs. 10.71 ± 6.64 (P < 0.05), respectively. ConclusionThe etiologies of most patients with RCC could be identified in the MDT clinic, and the cough-related symptoms of a significant number of patients with RCC improved in a short period.

Targeting Non-V600 Mutations in BRAF: A Single Institution Retrospective Analysis and Review of the Literature.

While successful treatment paradigms for BRAF V600 mutations have been developed, 10% of BRAF mutations are not at V600 and lack a standard treatment regimen. This study summarizes the current body of knowledge on the treatment of non-V600 mutations and reports a single institution experience. We conducted a literature review to summarize relevant preclinical and clinical published data on the response of non-V600 mutations to targeted therapies. We performed a retrospective analysis of INOVA Schar Cancer patients registered in our Molecular Tumor Board database with non-V600 BRAF mutations who were recipients of targeted therapy and assessed their time to next treatment and best response. Published preclinical and clinical data have demonstrated limiting results in the response of non-V600 mutated cancers to targeted therapies. Response rates were variable for the major classes of BRAF mutations including class II and class III mutations as well as, BRAF fusions. Data collected from our INOVA cohort offered promising results with one patient achieving partial remission and two patients achieving stable disease. This article reflects the current understanding of targeted therapies in non-V600 mutations. Further large-scale studies separating BRAF mutations based on their mechanism of activation will expand our understanding.