Probability Of Remission Research Articles

Factors not considered in the study of drug-resistant epilepsy: Psychiatric comorbidities, age, and gender.

In basic research and clinical practice, the control of seizures has been the most important goal, but it should not be the only one. There are factors that remain poorly understood in the study of refractory epilepsy such as the age and gender of patients and the presence of psychiatric comorbidities. It is known that in patients with drug‐resistant epilepsy (DRE), the comorbidities contribute to the deterioration of the quality of life, increase the severity, and worsen the prognosis of epilepsy. Some studies have demonstrated that patients diagnosed with a co‐occurrence of epilepsy and psychiatric disorders are more likely to present refractory seizures and the probability of seizure remission after pharmacotherapy is reduced. The evidence of this association suggests the presence of shared pathogenic mechanisms that may include endocrine disorders, neuroinflammatory processes, disturbances of neurotransmitters, and mechanisms triggered by stress. Additionally, significant demographic, clinical, and electrographic differences have been observed between women and men with epilepsy. Epilepsy affects the female gender in a greater proportion, although there are no studies that report whether refractoriness affects more females. The reasons behind these sex differences are unclear; however, it is likely that sex hormones and sex brain differences related to chromosomal genes play an important role. On the other hand, it has been shown in industrialized countries that prevalence of DRE is higher in the elderly when compared to youngsters. Conversely, this phenomenon is not observed in developing regions, where more cases are found in children and young adults. The correct identification and management of these factors is crucial in order to improve the quality of life of the patients.

Novi terapijski agensi u lečenju neurosarkoidoze

Neurosarcoidosis is a relatively common extrapulmonary form of sarcoidosis. It is characterized by variable clinical presentation, low probability of spontaneous remission, and significant impact on the quality of life, as well as potential increase in mortality. In addition to corticosteroids, other drugs are used in the treatment of neurosarcoidosis, such as methotrexate, azathioprine, mycophenolate mofetil, tumor necrosis factor a (TNF-a) inhibitors, infliximab and adalimumab. In this paper, by reviewing the available literature, we have attempted to consolidate the current knowledge and novelties in the treatment of neurosarcoidosis, for the purpose of assisting physicians in their day-to-day clinical work. Previous studies still favor pulsed doses of corticosteroids, while other forms of therapy have proven beneficial only in individual cases. However, it should be noted that additional research is needed in order to successfully develop individual therapy.

A glance into the future of diagnosis and treatment of spondyloarthritis.

The last two decades have seen major developments in the field of spondyloarthritis (SpA), but there are still important unmet needs to address. In the future, we envisage important advances in the diagnosis and treatment of SpA. In the diagnosis of SpA, the use of online and social media tools will increase awareness of the disease and facilitate the referral of patients to rheumatology clinics. In addition, more specific diagnostic tests will be available, especially advanced imaging methods and new biomarkers. This will allow most patients to be diagnosed at an early stage of the disease. In the treatment of SpA, an increasing number of novel treatment targets can be expected, most of which will be directed against intracellular enzymes. We hope to see more strategy trials shaping treatment pathways in SpA and accommodating principals of precision medicine. Approved treatment options will be available for both axial and peripheral SpA. We also hope to intervene not only at the inflammation level but also at the level of underlying immunological processes that might be associated with a higher probability of long-standing remission if not a cure. Finally, artificial intelligence techniques will allow for the analysis of large-scale data to answer relevant research questions for the diagnosis and management of patients with SpA.

Clinical effects of CD200 on the outcome of acute myeloid leukemia patients with diverse treatments

CD200 has been associated with a poor prognosis in acute myeloid leukemia (AML). However, the outcome for AML remains heterogeneous and relies more heavily on treatment procedures received by patients. This study aimed to evaluate the correlations between CD200 expression and its prognostic significance in AML treated using diverse treatments. 160 AML patients treated using different chemotherapeutic approaches were retrospectively reviewed from 2018 to 2021, and the effects of CD200 expression on disease outcomes were evaluated. CD200 expressed in 100/160 (62.5%) cases, defined as the CD200-positive (CD200⁺) group, while the remaining cases were identified as the CD200-negative (CD200⁻) group. The CD200⁺ group had a significantly lower probability of complete remission after the first induction chemotherapy, both in univariate (<i>P</i>=0.002) and multivariate (<i>P</i>=0.023) analyses. In the entire population, CD200 expression exerted no significant effect on disease-free survival (DFS) (<i>P</i>=0.837) nor overall survival (OS) (<i>P</i>=0.155). In the subgroup analysis, CD200 negatively affected OS in patients receiving less-intensive treatments (<i>P</i>=0.005) and those receiving chemotherapy alone (<i>P</i>=0.019). In conclusion, CD200 positive indicates a low remission rate and further reduces long-term survival in patients receiving less-intensive approaches and chemotherapy-alone. Intensive chemotherapy and stem cell transplantation may reduce the adverse effects of CD200 expression on AML patients.

Hepatitis B Viral Infection Associated with Cirrhosis and Hepatocellular Carcinoma

In humans, the hepatitis B virus causes a persistent infection in the liver. Recently, 3.5 percent of the worldwide been infected with HBV on a long-term basis. It is a chronic, dynamic disease that can be managed with medication but not cured. With continuous inflammation and viremia, the risk of final liver disease and hepatocellular cancer rises. Out of the 24 million people afflicted, 15% to 40% develop cirrhosis, leading to a failing liver or carcinoma. Chronic HBV infection usually progresses through several clinical phases, each of which might continue for decades. vaccination and, less by the use of antivirals to lower the viral burden of individuals are reducing the incidence of HBV infections. Serum and liver demonstrations diagnostic markers that are well defined and verified allow for assessing disease worsening, virus increase status, patient risk stratification, and therapy options. Novel chemicals are being tested to achieve HBV surface antigen clearing, a serological state linked to a better probability of remission after treatment termination, and a decreased risk of cirrhosis and hepatcellularcacer. Hepatcellularcarcinma (HCC) is the most frequent type of first seen liver cancer and a leading cause of cancer-related death globally. HCC is the ninth most significant cause of cancer death in the United States. Advancingstrat, screens, and new techno in diagnosis and treatment, the incidence and death of cancer continues to climb. Regardless of the cause, cirrhosis remains the most critical risk factor for the development of HCC.

Evaluating the perceived utility of an artificial intelligence-powered clinical decision support system for depression treatment using a simulation center

Aifred is a clinical decision support system (CDSS) that uses artificial intelligence to assist physicians in selecting treatments for major depressive disorder (MDD) by providing probabilities of remission for different treatment options based on patient characteristics. We evaluated the utility of the CDSS as perceived by physicians participating in simulated clinical interactions. Twenty physicians who were either staff or residents in psychiatry or family medicine completed a study in which they had three 10-minute clinical interactions with standardized patients portraying mild, moderate, and severe episodes of MDD. During these scenarios, physicians were given access to the CDSS, which they could use in their treatment decisions. The perceived utility of the CDSS was assessed through self-report questionnaires, scenario observations, and interviews. 60% of physicians perceived the CDSS to be a useful tool in their treatment-selection process, with family physicians perceiving the greatest utility. Moreover, 50% of physicians would use the tool for all patients with depression, with an additional 35% noting that they would reserve the tool for more severe or treatment-resistant patients. Furthermore, clinicians found the tool to be useful in discussing treatment options with patients. The efficacy of this CDSS and its potential to improve treatment outcomes must be further evaluated in clinical trials.

Quantification of Glomerular Structural Lesions: Associations With Clinical Outcomes and Transcriptomic Profiles in Nephrotic Syndrome

The current classification system for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) does not fully capture the complex structural changes in kidney biopsies nor the clinical and molecular heterogeneity of these diseases. Prospective observational cohort study. 221 MCD and FSGS patients enrolled in the Nephrotic Syndrome Study Network (NEPTUNE). The NEPTUNE Digital Pathology Scoring System (NDPSS) was applied to generate scores for 37 glomerular descriptors. Time from biopsy to complete proteinuria remission, time from biopsy to kidney disease progression (40% estimated glomerular filtration rate [eGFR] decline or kidney failure), and eGFR over time. Cluster analysis was used to group patients with similar morphologic characteristics. Glomerular descriptors and patient clusters were assessed for associations with outcomes using adjusted Cox models and linear mixed models. Messenger RNA from glomerular tissue was used to assess differentially expressed genes between clusters and identify genes associated with individual descriptors driving cluster membership. Three clusters were identified: X (n= 56), Y (n= 68), and Z (n= 97). Clusters Y and Z had higher probabilities of proteinuria remission (HRs of 1.95 [95% CI, 0.99-3.85] and 3.29 [95% CI, 1.52-7.13], respectively), lower hazards of disease progression (HRs of 0.22 [95% CI, 0.08-0.57] and 0.11 [95% CI, 0.03-0.45], respectively), and lower loss of eGFR over time compared with X. Cluster X had 1,920 genes that were differentially expressed compared with Y+Z; these reflected activation of pathways of immune response and inflammation. Six descriptors driving the clusters individually correlated with clinical outcomes and gene expression. Low prevalence of some descriptors and biopsy at a single time point. The NDPSS allows for categorization of FSGS/MCD patients into clinically and biologically relevant subgroups, and uncovers histologic parameters associated with clinical outcomes and molecular signatures not included in current classification systems.

Predicting Dynamic Clinical Outcomes of the Chemotherapy for Canine Lymphoma Patients Using a Machine Learning Model.

First-line treatments of cancer do not always work, and even when they do, they cure the disease at unequal rates mostly owing to biological and clinical heterogeneity across patients. Accurate prediction of clinical outcome and survival following the treatment can support and expedite the process of comparing alternative treatments. We describe the methodology to dynamically determine remission probabilities for individual patients, as well as their prospects of progression-free survival (PFS). The proposed methodology utilizes the ex vivo drug sensitivity of cancer cells, their immunophenotyping results, and patient information, such as age and breed, in training machine learning (ML) models, as well as the Cox hazards model to predict the probability of clinical remission (CR) or relapse across time for a given patient. We applied the methodology using the three types of data obtained from 242 canine lymphoma patients treated by (L)-CHOP chemotherapy. The results demonstrate substantial enhancement in the predictive accuracy of the ML models by utilizing features from all the three types of data. They also highlight superior performance and utility in predicting survival compared to the conventional stratification method. We believe that the proposed methodology can contribute to improving and personalizing the care of cancer patients.

Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients

Chimeric antigen receptor (CAR) T cells targeting the CD19 antigen are effective in treating adults and children with B-cell malignancies. Place-of-care manufacturing may improve performance and accessibility by obviating the need to cryopreserve and transport cells to centralized facilities. Here we develop an anti-CD19 CAR (CAR19) comprised of the 4-1BB co-stimulatory and TNFRSF19 transmembrane domains, showing anti-tumor efficacy in an in vivo xenograft lymphoma model. CAR19 T cells are manufactured under current good manufacturing practices (cGMP) at two disparate clinical sites, Moscow (Russia) and Cleveland (USA). The CAR19 T-cells is used to treat patients with relapsed/refractory pediatric B-cell Acute Lymphocytic Leukemia (ALL; n = 31) or adult B-cell Lymphoma (NHL; n = 23) in two independently conducted phase I clinical trials with safety as the primary outcome (NCT03467256 and NCT03434769, respectively). Probability of measurable residual disease-negative remission was also a primary outcome in the ALL study. Secondary outcomes include complete remission (CR) rates, overall survival and median duration of response. CR rates are 89% (ALL) and 73% (NHL). After a median follow-up of 17 months, one-year survival rate of ALL complete responders is 79.2% (95%CI 64.5‒97.2%) and median duration of response is 10.2 months. For NHL complete responders one-year survival is 92.9%, and median duration of response has not been reached. Place-of-care manufacturing produces consistent CAR-T cell products at multiple sites that are effective for the treatment of patients with B-cell malignancies.

Probability of Remission of the Main Epileptic Syndromes in Childhood.

To determine the long-term probability of remission without antiepileptic treatment of common epileptic syndromes and of children without a specific syndromic diagnosis. All children less than 14 years old with 2 or more unprovoked seizures seen at our hospital between June 1, 1994, and March 1, 2011 (n = 680), were included and prospectively followed up until August 15, 2020. Syndromic diagnosis was made retrospectively but blinded to subsequent evolution, employing the data available at 6 months after diagnosis and under predefined operational criteria. The Kaplan-Meier estimate of the probability of achieving a remission period of at least 5 years, with neither seizures nor antiepileptic treatment at 14 years was 97% for well-defined childhood epilepsy with centrotemporal spikes, 82% for uncertain childhood epilepsy with centrotemporal spikes, 85% for well-defined Panayiotopoulos syndrome, 88% for uncertain Panayiotopoulos syndrome, 93% for nonfamilial self-limited infantile epilepsy, 100% for familial self-limited infantile epilepsy, 86% for absence epilepsy, 6% for juvenile myoclonic epilepsy, 71% for cryptogenic West syndrome, 72% for patients with no associated neurologic deficits and no specific syndromic diagnosis, 65% for symptomatic West syndrome, and 40% for patients with associated neurologic deficits and no specific syndromic diagnosis. The study results highlight the long-term outcomes of the main epileptic syndromes and also of the patients with no syndromic diagnosis.

Clinical predictive model for the 1-year remission probability of IgA vasculitis nephritis

PurposeEarly remission of Immunoglobulin A vasculitis nephritis (IgAVN) substantially affects its prognosis. In this work, a multivariate model to predict the 1-year remission probability of patients with IgAVN was developed on the basis of clinical laboratory data. MethodsData of 187 patients with IgAVN confirmed by renal biopsy were retrospectively assessed. Least absolute shrinkage and selection operator regression analysis were conducted to establish a multivariate logistic regression model. A nomogram based on the multivariate logistic regression model was constructed for easy application in clinical practice. Concordance index, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and clinical impact curves (CIC) were used to evaluate the predictive accuracy and clinical value of this nomogram. ResultsThe predictive factors contained in the multivariate model included duration, gender, respiratory infection, arthritis, edema, estimated glomerular filtration rate, 24 h urine protein, uric acid, and renal ultrasound intensity. The area under the curves (AUC) of the nomogram in the training set and testing set were 0.814 and 0.822, respectively, indicating its good predictive ability. Moreover, the DCA curve and CIC revealed its clinical utility. ConclusionThe developed multivariate predictive model combines the clinical and laboratory factors of patients with IgAVN and is useful in the individualized prediction of the 1-year remission probability aid for clinical decision‐making during treatment and management of IgAVN.

Quantifying Remission Probability in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic progressive disorder and is associated with significant morbidity and mortality. The concept of T2DM remission and the reversal of diabetic parameters to normal levels has been gaining momentum over the past years. T2DM remission is increasingly being recognized by various global guidelines. Multiple models have been developed and validated for quantifying the extent of remission achieved. Based on favorable clinical evidence, T2DM remission can be considered as the therapeutic goal in diabetes management and, in select cases, as an alternative to expensive treatment options, which can be burdensome as T2DM progresses. This narrative review discusses the available strategies, such as lifestyle interventions, physical activity, bariatric surgery, medical nutrition therapy, and non-insulin glucose-lowering medications, for achieving T2DM remission. Although the concept of T2DM remission has emerged as a real-world option, effective implementation in routine clinical practice may not be feasible until long-term studies prove the efficacy of different approaches in this regard.

Complete Versus Incomplete Hematologic Recovery after CAR T Cell Therapy: Implications for Relapse Free Survival and Overall Survival in Pediatric and Young Adult Patients with Relapsed/Refractory B-ALL

Background: Anti-CD19 Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a mainstay in the treatment of patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). While trials have shown encouraging survival rates, up to 50% of patients receiving CART eventually relapse. Identification of risk factors for subsequent relapse is crucial, as this could allow tailored surveillance and treatment approaches for high-risk patients, potentially leading to improved morbidity and mortality. Complete remission with incomplete hematologic recovery (CRi) has been associated with decreased remission duration and overall survival in acute leukemias. As count suppression following CAR T cell therapy is frequently seen, this study evaluated CRi as a prognostic marker for worse relapse-free (RFS) and overall survival (OS) after CAR T cell therapy in comparison to complete remission with hematologic recovery (CR).Methods: Patients with r/r ALL who achieved a complete morphologic remission after receiving anti-CD19 CAR T cell treatment with the 4-1BB-containing products CTL019 or humanized CART19 in the context of a clinical trial (NCT01626495, NCT02374333, NCT02228096, NCT02435849, NCT02906371) or commercial product (tisagenlecleucel) at Children's Hospital of Philadelphia from 4/2012-4/2019 were identified. Patients who received prior CAR therapy, and those with Trisomy 21 were excluded. Demographic, disease and treatment characteristics, and outcome data were abstracted from the medical record or clinical trial datasets. CR was defined as achieving a morphologic remission with both an absolute neutrophil count (ANC) ≥1,000/µL and a transfusion-independent platelet count ≥100,000/µL at any time between 27-33 days after CAR T cell infusion, whereas those achieving a morphologic remission without complete hematologic recovery were defined as CRi. RFS and OS were described for each cohort. Exposure-outcome association was assessed via the log-rank test and multivariable Cox proportional hazard regression.Results: Of the 206 patients included in the analysis, 104 (51%) achieved CR, 102 (49%) CRi. Forty patients (39%) met criteria for CRi with both ANC <1000/µL and platelets <100,000/µL, 40 (39%) for isolated thrombocytopenia, and 20 (20%) for neutropenia alone. Median age at leukemia diagnosis was 7 years (range 0.2-24), and at CAR T cell infusion was 12 years (range 1-29), with 48% undergoing a prior allogeneic stem cell transplant (HSCT), 32% with high risk cytogenetics, and 10% with prior blinatumomab treatment, none of which differed between the CR and CRi groups (Table 1). The number of relapses prior to CAR T cell referral was different between the groups (p=0.003), with more CR patients having been referred for primary refractory disease (25% vs 9.8%), and more CRi patients for first relapse (34% vs 18%). More CRi patients had >25% bone marrow blasts (43% vs 19%) at infusion, whereas more CR patients were MRD-negative (50% vs 30%) at infusion (p=0.002). CRi patients were also more likely to have Grade 3/4 CRS (38% vs 6.7%). Median length of follow-up for patients with CR was 39 months (range 7-89), which was not statistically significantly different than for those patients with CRi (41 months, 11-98, p=0.875). There was no difference in RFS when stratified by hematologic recovery (Figure 1, p=0.2165), with RFS at 36 months for CR of 57% (47-69) and CRi of 46% (36-59). OS was significantly lower (Figure 2, p=0.0081) for those with CRi, with 36-month OS for CR of 81% (74-89), and for CRi of 63% (54-73). In multivariable analysis adjusting for sex, prior blinatumomab, relapse number, disease burden at infusion, and maximum CRS grade, CR was not associated with either RFS (HR 0.76 [95%CI 0.50-1.17] p=0.2182) or OS (HR 0.74 [95%CI 0.43-1.29] p=0.2908), in comparison to CRi, Table 2.Discussion: Complete remission with incomplete hematologic recovery, manifesting as neutropenia and/or thrombocytopenia, at the first disease assessment following CAR T cell infusion should not be regarded as a harbinger of relapse and demonstrates that patients with CRi have similar probability of durable remission without further therapy. Anticipatory guidance should be provided to patients, and their families, that CRi is more frequently seen in patients who experience high grade CRS, who have high disease burden at infusion, and who are treated in first relapse. [Display omitted] DisclosuresCallahan: Novartis: Speakers Bureau. Rheingold: Optinose: Other: Spouse's current employment; Pfizer: Research Funding. Grupp: Novartis, Roche, GSK, Humanigen, CBMG, Eureka, and Janssen/JnJ: Consultancy; Novartis, Adaptimmune, TCR2, Cellectis, Juno, Vertex, Allogene and Cabaletta: Other: Study steering committees or scientific advisory boards; Novartis, Kite, Vertex, and Servier: Research Funding; Jazz Pharmaceuticals: Consultancy, Other: Steering committee, Research Funding. Maude: Wugen: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding.

Are Delays in the Diagnosis and Treatment of Acute Leukemia in a Middle-Income Country Associated with Poor Outcomes?

Introduction:Mexico, like other Middle-Income Countries (MIC), faces many challenges in the care of patients with cancer. The number of practicing physicians is lower than the recommended for the OECD, there is <1 hematologist/100,000 people, and the attention is centralized in big cities .It has been reported that children with acute lymphoblastic leukemia (ALL) suffer from significant diagnosis delays in Latin America but this has not been assessed in adults.There is a well-described association between delays in diagnosis and poor outcomes in some solid tumors. Acute leukemia (AL) is associated with a shorter time-to-diagnosis when compared with other malignancies. However, its impact on early death (ED) or long-term outcomes is not clear.Methods:We designed a retrospective single center study with the main objective of analyzing the diagnosis and treatment delays in adults with newly diagnosed AL in a referral center in Mexico City.We defined the following intervals. Patient interval (PI): from the first symptom to the first medical consultation. Diagnostic interval (DI): from the first medical consultation to the diagnosis. Treatment interval (TI): from the diagnosis to the treatment initiation. Total interval (TTI): from the first symptom to the treatment initiation.We evaluated patients ≥18 years diagnosed with ALL, acute myeloid leukemia (AML) or acute promyelocytic leukemia (APL) between January 2015-March 2020.Results:We included 187 patients with a median age of 36 years (18-90), the majority adolescent and young adults (AYA) (54.4%): 102 ALL, 56 AML and 29 APL.Almost half of them (43.4%) lived in Mexico City, only 20.3% had a professional degree and 80.2% had a low socioeconomic status (LSE).The majority (85.5%) received intensive chemotherapy, 6.7% a non-intensive regimen and 7.8% supportive care.The patients consulted a median of 3 different physicians (range 1-9) before the hematologist. The median interval times were: PI 14 days (0-182), DI 10 days (0-221), TI 4 days (0-22) and TTI 32 days (3-252).The TI and TTI were significantly shorter in patients with APL when compared with ALL and AML: TI of 1 vs. 4 and 3 days (p=0.001) and TTI of 21 vs. 35 and 31 days (p=0.002). The PI and DI were not different between AL subtypes (figure 1).Patients with comorbidities had a significant shorter DI: 9 (0-65) vs. 11 days (0-221), p=0.045. Patients living in Mexico City had a significant shorter DI: 7 (0-221) vs. 11.5 days (0-148), p=0.015; and TTI: 28 (3-252) vs. 34 days (3-183), p= 0.030.A DI > 3 weeks was associated with a higher risk of neutropenic colitis (15.9% vs. 6.0%): OR 2.94 (CI 1.03-8.43), p= 0.057.The 30-day and 60-day mortality were 12.8% and 19.3%, mainly derived from infectious complications in 58.3% and 69.4%. Risks factors for ED are summarized in table 1.Twenty patients had a TTI ≥ 85 days: 60% were AYA, the majority ALL (ALL 11, AML 7 and APL 2), with LSE (89.5%) and living outside Mexico City (70%). The 30-day and 60-day mortality were 15% and 25% for this group.None of the intervals was associated with a higher-risk of ED with the exception of longer TI for patients with APL who died within 60 days (2.5 vs. 1 day, p=0.024). None of the intervals was associated with complete remission probability or long-term overall survival.Conclusions:To our knowledge, this is the first insight into the delays in adults with AL in a MIC. Surprisingly, the median intervals are not different when compared with high-income countries (HIC). However, the upper limit of the ranges is significantly higher in Mexico than in the UK registry (TTI in Mexico for ALL and AML are 221 and 252 days vs. 64 and 85 days in the UK). In our study, delays do not impact in short or long-term outcomes. But we believe that there may be a significant number of patients with more aggressive disease, who died before diagnosis. ED is still high in Mexico and the leading cause is infections.Patients from Mexico City had shorter diagnostic intervals when compared to patients living outside the city. This could be related with structural barriers of the health system that make timely cancer care inaccessible. Patient navigation is a promising intervention to address cancer disparities that allows reducing times. Most of the patient navigation models are focus on solid tumors, in screening and palliative care and in HIC. In our population, with a high frequency of ALL and APL in AYAs with a good chance of cure, a patient navigation model needs to be adapted. [Display omitted] DisclosuresApodaca: Abbvie: Speakers Bureau; Asofarma: Consultancy, Speakers Bureau; Sanofi: Consultancy. Rangel-Patiño: Bristol: Consultancy; Abbvie: Speakers Bureau. Demichelis: ASH: Research Funding; Gilead: Consultancy; Bristol/Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy; Novartis: Consultancy, Research Funding, Speakers Bureau; AMGEN: Consultancy, Speakers Bureau; Astellas: Consultancy; Abbvie: Consultancy, Speakers Bureau.

Comparative Efficacy of Antidepressants for Symptoms Remission of Gastroesophageal Reflux: A Bayesian Network Meta-analysis of Randomized Controlled Trials.

The present study aimed to compare and evaluate the efficacy of antidepressants in remission of esophageal reflux symptoms. A comprehensive literature review was performed including sources published on MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials (Cochrane), Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese VIP Information Databases (VIP), Chinese Biology Medicine disc (CBM), and Wan-Fang databases for randomized controlled trials, published up to and including March 31, 2020. We analyzed relevant randomized, placebo-controlled trials reporting the effect of antidepressant therapy in relieving esophageal reflux symptoms ADDIS 1.16.8 was used to perform the network meta-analysis. Furthermore, we performed a split analysis to test inconsistency, and rank probability was complemented for comparison among antidepressants. A total of 10 randomized controlled trials (RCTs) examining the effects of antidepressants, selective 5-HT reabsorption inhibitor (SSRI), 5-HT 1A receptor agonist (5-HT1AA), tricyclic antidepressants (TCAs), and the complex of flupentixol-melitracen (FM) were included. Flupentixol-melitracen and SSRIs exhibited a significantly higher rate of remission than placebo. However, there was no statistically significant difference among different antidepressants compared. Rank probability showed that FM exhibited the highest probability of rank 1 compared with other antidepressants and placebo. This network meta-analysis of RCTs supported the use of FM and SSRIs as a potentially effective regimen for symptom remission of gastroesophageal reflux. Furthermore, according to our analysis, FM represents the most efficient antidepressant with highest probability of symptom remission.

Long-term results of treatment of pharmacoresistant temporal lobe epilepsy

The aim of the study wasto evaluate the long-term results ofsurgicaltreatment of patients with pharmacoresistant epilepsy.Materials and methods. A retrospective analysis of treatment outcomes in patients with drug-resistant temporal lobe epilepsy was performed. According to the inclusion and exclusion criteria, 96 patients were selected for the study. Group 1 contained 49 operated patients with MR-positive epilepsy and Group 2 contained 47 operated patients with MR-ne‑ gative epilepsy. The control group consisted of 53 unoperated patients. The outcomes ofsurgical treatment were assessed after 6, 12, and 24 months. Results. Unfavorable outcomes occurred more frequently among nonoperated patients compared to both surgical groups (p &lt;0.001). The probability of the 2-year remission after surgery in operated MRI positive patients was 60 %, in MRI negative group was 45 %, and in conservative group – only 2 %. The mean duration of the seizures-free period was greatest̆in the MRI positive surgical group (15.4 ± 1.5 months), and shortest in the control group (3.3 ± 0.9 months).Conclusion. The presented results prove the effectiveness and safety of surgical treatment of patients with temporal lobe epilepsy.

The effect of blood levels of heparan sulfate, VCAM-1 and ICAM-1 in combination with clinical and morphological features of the course of glomerulonephritis on the probability of achieving remission

Objective: to analyze the effect of adhesion molecules (ICAM-1, VCAM-1) and blood heparan sulfate in combination with clinical and morphological signs on the likelihood of remission in glomerulonephritis. Material and methods: 80 patients with glomerulonephritis aged 35.7±10.9 years were included. Serum levels of ICAM-1, VCAM-1 and heparan sulfate were determined in all patients by quantitative enzyme immunoassay. Puncture nephrobiopsy was performed with verification of the form of nephritis and determination of signs of TIC, TIV, glomerulosclerosis. Results: It was shown that high values of heparan sulfate and uric acid in the blood reduce the likelihood of achieving remission in glomerulonephritis. Also, high values of heparan sulfate in the blood against the background of pronounced TIC or TIV were accompanied by a decrease in the probability of remission. An increase in the level of ICAM-1 in the blood, combined with an increase in age, the level of fibrinogen in the blood, as well as an increase in the phenomena of TIC, TIV and glomerulosclerosis, reduce the likelihood of achieving remission in glomerulonephritis. It was also shown that an increase in the level of VCAM-1 in the blood against the background of an increase in the patient’s age, hyperuricemia, an increase in the phenomena of TIV, TIC and glomerulosclerosis is accompanied by a decrease in the probability of achieving remission. We have compiled nomograms for assessing the prognosis of remission development. Conclusion: the assessment of the levels of heparan sulfate, ICAM-1 and VCAM-1 in the blood, together with a number of clinical and morphological signs, is an important tool for predicting the effectiveness of glomerulonephritis therapy.

Frequency of FLT3 Internal Tandem Duplications in Adult Syrian Patients with Acute Myeloid Leukemia and Normal Karyotype.

Objective:Activating mutations of the fms-like tyrosine kinase 3 gene (FLT3) by internal tandem duplications (ITDs) in the juxtamembrane domain (JMD) have been reported in ~30% of adult acute myeloid leukemia (AML) patients with cytogenetically normal karyotype (CN). However, FLT3/ITD mutations are frequently accompanied with leukocytosis, high percentage of blasts in bone marrow (BM), and increased the risk of treatment failure in AML patients. FLT3-ITD mutated AML patients mainly with normal karyotype have higher relapse probability and shorter duration of complete remission (CR) after chemotherapy, so FLT3-ITD mutation is considered as an independent poor prognostic factor in AML. Methods: FLT3-ITD and FLT3-KTD were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism- PCR (RFLP-PCR) in 44 adults AML patients with cytogenetically normal karyotype (AML-CN) at diagnosis to characterize FLT3 status. The results were correlated with the prognostic factors. Results:In this study, FLT3-ITD mutations were identified in 7 (15.9%) of the 44 AML-CN patients. Among the 7 patients with FLT3/ITD mutations, 6 patients revealed a typical ITDs mutation (fragment size was 329 bp) and one patient showed untypical ITD mutation (fragment size was ~400 bp). Whereas 37 patients (61.7%) were FLT3-ITD. None of all AML-CN patients examined showed FLT3-KTD mutations. Conclusions:Our results support that FLT3-ITD are independent adverse prognostic factors for elderly AML-CN patients and are associated with low overall survival (OS), low rate of CR, high relapse rate (RR), and high percentage of BM blast at diagnosis. We concluded, FLT3 mutation analysis should be performed as a routine test in AML-CN patients.

The PRolaCT studies \u2014\xa0a study protocol for a combined randomised clinical trial and observational cohort study design in prolactinoma

BackgroundFirst-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size.MethodsWe present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naïve patients; PRolaCT-2: patients with limited duration of DA treatment (4–6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months.DiscussionEarly or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine.Trial registrationUS National Library of Medicine registry (ClinicalTrials.gov) NCT04107480. Registered on 27 September 2019, registered retrospectively (by 2 months).

Body mass index and atypical balance as predictors of winter depression remission in cognitive-behavioral therapy and light therapy

BackgroundEfficacious treatments for winter seasonal affective disorder (SAD) include light therapy (LT) and cognitive-behavioral therapy (CBT-SAD); however, baseline characteristics may differentially predict treatment outcomes. This study investigated body mass index (BMI) and atypical balance (the proportion of atypical depression symptoms), as predictors of depression remission. MethodsThe parent study randomized 177 adults diagnosed with Major Depression, Recurrent with Seasonal Pattern to 6-weeks of CBT-SAD (n = 88) or LT (n = 89) and followed participants one and two winters later. At baseline, BMI was measured and atypical balance was derived using the Structured Interview Guide for the Hamilton Rating Scale for Depression–Seasonal Affective Disorder Version (SIGH-SAD) as 8-item atypical subscale score/total SIGH-SAD score × 100. Depression remission was defined using standard SIGH-SAD cutpoints. Hierarchical logistic regressions tested the main effects of treatment modality, BMI, and atypical balance and their interactive effects on depression remission at post-treatment and follow-ups. ResultsThe BMI × treatment and atypical balance × treatment interactions significantly predicted depression remission at second winter follow-up. The probability of remission was higher in CBT-SAD than LT at BMI ≤ 26.1 and atypical balance ≤ 40.3%. This predictive relationship survived when adjusting atypical balance for BMI, but not vice-versa. LimitationsParticipants were predominantly White and older. BMI does not account for muscle mass or fat distribution. ConclusionsBMI and atypical balance prescriptively predicted higher likelihood of depression remission two winters following CBT-SAD but not LT. This work informs clinical decision-making and precision medicine efforts.