Tracking Study on the Relapse and Aftercare Effect of Drug Patients Released From a Compulsory Isolated Detoxification Center

Background and AimsThere are no accurate statistical data on the relapse rate of drug abstainers after compulsory detoxification in China. This study aimed to collect relapse data for drug abstainers through follow-up visits, verify the effectiveness of professional social worker services and explore significant factors affecting relapse.Design and SettingThe drug abstainers released from Guangzhou T Compulsory Isolated Detoxification Center were randomly divided into two groups. The difference between the experimental group and the control group is that assistance services were provided by social workers to the former.ParticipantsThe study included 510 drug abstainers released from T Center, including 153 in the experimental group and 357 in the control group.MeasurementsDemographic information, history of drug abuse, and motivation for drug rehabilitation (SOCRATES) were collected 1 month prior to drug abstainer release from compulsory detoxification. Then, the relapse situation after their release was tracked according to fixed time points.FindingsThe overall relapse rate of 510 drug abstainers after their release from compulsory detoxification was 47.6%. The average survival time to relapse based on survival analysis was 220 days (N = 486), as calculated with Bayesian estimation by the MCMC method. The average survival times to relapse of the experimental group and control group were 393 and 175 days, respectively. By taking the specific survival time as the dependent variable and the group as the control variable (OR = 25.362), logistic regression analysis showed that marital status (OR = 2.666), previous compulsory detoxification experience (OR = 2.329) and location of household registration (OR = 1.557) had a significant impact on the survival time to relapse.ConclusionsThe occurrence of relapse among drug patients released from compulsory detoxification can be delayed effectively through the intervention of professional social worker services. Regardless of whether patients receive aftercare after compulsory detoxification, drug-using patients who are single, have multiple detoxification experiences and whose households are registered in other provinces deserve special attention. Relevant suggestions to avoid relapse are provided.

The biopsychosocial-spiritual factors influencing relapse of patients with schizophrenia

Objective: High relapse rate of patients with schizophrenia has a large impact on patients and their families that can be reviewed from biopsychosocial and spiritual factors. Determining all the potential risk factors of relapse in schizophrenia can help increase awareness of physicians, patients, and families. Physicians are the ones who examine patients and have responsibility to manage and educate them and expect to prevent relaps. This study analyze various biopsychosocial and spiritual factors affecting relapse occurrence in patients with schizophrenia. Methods: Cross sectional observational analytic study on 226 subjects with schizophrenia in three places in East Java, Indonesia, namely Soetomo Academic Hospital Surabaya (33.2%), Menur Hospital Surabaya (32.7%), and Radjiman Wediodiningrat Mental Hospital Lawang (34.1%) that met the inclusion and exclusion criteria. Data collection including 33 biopsychosocial and spiritual factors and were analyzed using bivariate and multivariate logistic regression. Results: Relapse rate within 1 year was 59.73%. There were 12 factors significantly affected the relapse of schizophrenia, namely history of physical disease of mothers during pregnancy ( p < .001; B = 27.31; 95% CI 3.96–188.52), presence of trigger ( p < .000; B = 6.25; 95% CI 2.61–14.96), negative beliefs ( p < .000; B = 4.94; 95% CI 2.10–11.61), hereditary factors ( p < .001; B = 4.84; 95% CI 1.93–12.10), insight ( p < .003; B = 4.27; 95% CI 1.62–11.27), 1-year GAF Scale ( p < .015; B = 3.79; 95% CI 1.30–11.09), response to treatment ( p < .006; B = 3.68; 95% CI 1.45–9.36), family knowledge ( p < .011; B = 3.23; 95% CI 1.31–7.93), history of head trauma ( p < .029; B = 3.13; 95% CI 1.13–8.69), medication side effects ( p < .028; B = 2.92; 95% CI 1.12–7.61), substance use history ( p < .031; B = 2.86; 95% CI 1.10–7.45), and occupation ( p < .040; B = 2.40; 95% CI 1.04–5.52). Conclusions: The 12 factors of biopsychosocial-spiritual are determinant to predict the risk of relapse in patients with schizophrenia. These factors should be emphasized in psychoeducation for patients and their families to enable intervention and relapse prevention.

Fertility-sparing surgery for patients with stage IC2 or IC3 epithelial ovarian carcinoma: any evidence of safety?

ObjectiveInvestigate the overall survival of patients with stage IC2/IC3 epithelial ovarian carcinoma undergoing fertility-sparing surgery.MethodsPatients aged <45 years diagnosed between January 2004 and December 2015 with epithelial ovarian carcinoma, who underwent surgical staging and had tumor involving the ovarian surface (IC2), malignant ascites or positive cytology (IC3), were identified in the National Cancer Database. The fertility-sparing surgery group included patients who had preservation of the uterus and the contralateral ovary while the radical surgery group included patients who had hysterectomy with bilateral salpingo-oophorectomy. Overall survival was evaluated following generation of Kaplan–Meier curves while a Cox model was constructed to control for tumor grade and performance of lymphadenectomy. A systematic review of the literature was performed and cumulative relapse rate among patients with IC2/IC3 disease who underwent fertility-sparing surgery was calculated.ResultsA total of 235 cases were identified; 105 (44.7%) patients underwent fertility-sparing surgery. There was no difference in overall survival between the fertility-sparing and radical surgery groups (p=0.37; 5- year overall survival rates 90.2% and 85%, respectively). After controlling for tumor grade and performance of lymphadenectomy, fertility-sparing surgery was not associated with worse overall survival (HR 1.22, 95% CI 0.56, 2.62). A systematic review identified 151 patients with stage IC2/IC3 disease who underwent fertility-sparing surgery. Cumulative relapse rate was 19.3% (n=29) while 12 (6.7%) deaths were reported. Median time to recurrence was 19 (range 1–128.5) months. Tumor recurrence involved the ovary exclusively in 42% (11/26) of patients, while 15% (4/26) had a lymph node, 35% (9/26) a pelvic/abdominal, and 8% (2/26) a distant tumor relapse.ConclusionsIn a large cohort of patients with stage IC2/IC3 epithelial ovarian carcinoma, fertility-sparing surgery was not associated with worse overall survival. However, based on a literature review, relapse rate is approximately 20%.

HIV-1 co-infection increases relapse rate and shortens survival in patients with visceral leishmaniasis

Patients co-infected with visceral leishmaniasis (VL) and HIV-1 (VL/HIV patients) suffer from recurrent VL relapses and increased mortality. The aim of our study was to test the hypothesis that HIV patients who present with their first episode of VL (primary VL/HIV patients) experience less relapses and lower mortality as compared to VL/HIV patients who have a previous history of VL relapses (recurrent VL/HIV patients). Our results show that primary VL/HIV patients have a lower parasite load and that their relapse-free survival is significantly longer. Relapses in both groups of patients occur independently of HIV viral load. Our clinical and immunological analyses of these patients at the time of diagnosis and during follow-up show that the poorer prognosis of recurrent VL/HIV patients is accompanied by lower weight gain and lower recovery of all blood cell lineages, as well as lower production of antigen-specific IFN-gamma, lower CD4+ T cell counts and higher expression levels of the inhibitory receptor PD1 on CD4+ and CD8+ T cells. We propose that in addition to the current treatments, novel interventions should be considered at the time of VL diagnosis in VL/HIV patients and suggest that improved anti-leishmanial and antiretroviral treatments, as well as immune therapy, through PD1/PDL-1 blockade and/or through IFN-gamma administration, could result in more efficient parasite killing and thereby reduce the relapse rate and improve survival.

Efficacy and Safety of Eltrombopag with or without Immunosuppressant in Patients with Relapsed/Refractory Acquired Aplastic Anemia: A Real-World Experience

Background: Eltrombopag (EPAG) with or without immunosuppressant (IST) has been applied in acquired aplastic anemia (AA), yet data of EPAG+IST in relapsed/refractory AA was limited, and no study has compared efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients. Aims: To evaluate and compare the efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients in a real-world setting. Methods: Data from patients diagnosed as acquired AA in our center were retrospectively collected. All the enrolled patients were refractory/relapsed to the standard IST for at least 6 months before EPAG. All patients had been treated with EPAG, which was started at 25 mg/day and increased every 2 weeks to a maximum of 150 mg/day until a best response was achieved. Meanwhile, some patients were treated with cyclosporin A (CsA) or tacrolimus (FK506) at the same time. EPAG had to be prescribed for at least 6 months before evaluation. Complete response (CR), overall response (OR) and relapse rate, as well as adverse events and factors which could affect efficacy were analyzed. Results: Totally 99 patients (83 non-severe AA (NSAA) and 16 SAA) were included in the study. The median age at EPAG initiation was 46 (13-88) years old, the median time of EPAG treatment was 11 (6-41) months and the median time of follow-up was 18 (6-41) months. 72 patients were treated with EPAG+IST, including 41 (56.9%) treated with EPAG+FK506 and 31 (43.1%) treated with EPAG+CsA. 27 patients were treated with EPAG alone. No significant difference was found between EPAG+IST group and EPAG group in patient baseline characteristics like age, male proportion, NSAA proportion, presence of PNH clone, proportion of previous ATG+CsA / CsA treatment, previous IST duration and dosage. With compatible follow-up time, EPAG exposure duration and dosage, there was no significant difference in OR/CR rate at 3 rd/6 th/12 th month between patients who was treated with EPAG+FK506 and EPAG+CsA. Under similar compatible baseline conditions, the OR rate was 33.3% vs 22.2% (P=0.284) at 3 rd month, 61.1% vs 37.0% (P=0.032) at 6 th month, and 67.2% vs 42.1% (P=0.051) at 12 th month for patients treated with EPAG+IST and EPAG alone, respectively, but no significant difference was found in time to response (3 (1-12) vs 3 (1-7) months, P=0.679) or CR rate at 3 rd/6 th/12 th month (6.9%/12.5%/20.7% vs 3.7%/7.4%/5.3%, P&gt;0.05) between the two groups. Relapse occurred at 6 th to 12 th month of EPAG treatment, and the relapse rate at 12 th month was 9.8% and 27.3% (P=0.154) for patients treated with EPAG+IST and EPAG alone, respectively. For patients treated with EPAG+IST, responders had a significantly higher baseline reticulocyte count (60.25 (11.5-230.5)×10 9/L vs 16.7 (6.6-56.6)×10 9/L, P=0.040) compared with non-responders. No predictive factors for the overall response were found for patients treated with EPAG alone. Adverse events which led to dosage regulation were gastrointestinal disorders (2.8% vs 3.7%, P=1.000), elevated creatinine (2.8% vs 0, P=0.599), elevated ALT (1.4% vs 0, P=1.000) and arthralgia (0 vs 3.7%, P=0.280) for patients with EPAG+IST and EPAG, respectively. No deaths were found in either group, while the clone evolution rate was 2.8% and 3.7% (P=1.000) in EPAG+IST and EPAG monotherapy group, respectively. Conclusion: EPAG+IST had higher OR rate than EPAG monotherapy with similar side effects for patients with relapsed/refractory acquired AA. Those with higher baseline reticulocyte count were more likely to respond to EPAG+IST. Key words: relapsed/refractory, aplastic anemia, eltrombopag, immunosuppressant, efficacy Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: In the presented study, eltrombopag was prescribed in relapsed/refractory aplastic anemia patients.

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Adults with Ph-like ALL

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) represents 20% of newly diagnosed adults with B cell ALL (B-ALL), with increased frequency in adults with Hispanic ethnicity. Ph-like ALL harbors a diverse range of genetic alterations with CRLF2-rearrangement/overexpression (CRLF2r) being the most common one. When treated with chemotherapy, Ph-like ALL is associated with inferior response, high relapse rate, and low overall survival (OS). Allogenic hematopoietic cell transplantation (alloHCT) is a well-established curative modality for adults with high-risk ALL. Considering that Ph-like ALL is a high-risk leukemia subtype, it is appealing to recommend alloHCT consolidation routinely for this entity in adults. However, large datasets describing alloHCT outcomes in patients with Ph-like ALL is lacking. In this study, we retrospectively analyzed archived DNA samples from 125 consecutive adult patients with Ph-negative ALL who underwent alloHCT in complete remission (CR) at our center between 2006 and 2020. Classification of Ph-like versus non-Ph-like was performed according to WHO 2017 classification using accumulative results from RNAseq, conventional cytogenetics, FISH, and whole genome array studies. A proprietary RNA sequencing assay covering 1,188 genomic regions from 235 genes was designed to detect all the clinically significant fusions and expressions for Ph-like ALLs. In addition, an algorithm employing the RNAseq data was developed to further aid in classification of Ph-like ALL. Boruta feature selection (R package "Boruta" version 7.0.0) was used to identify the most informative genes for prediction with an out-of-bag error of 9.62%. The following 24 genes were identified: CCND2, SOX11, PAX5, DENND3, RARA, MME, ID4, SH3BP5, HOXA9, CA6, MUC4, CYB5R2, CD97, EPOR, IL2RA, RAB29, PDGFRA, MLLT4, RHOA, JAK2, DNM2, ASXL1, BCL2A1, and KDR. The results were used to predict Ph-like status by a Random Forest model (R package "randomForest" version 4.6-14) that generates a probability/similarity score of Ph gene expression profile (Ph score). The testing samples with Ph score over 50% and without other subtype-defining lesions are defined as Ph-like. We identified Ph-like genetic alterations in 66 (53%) patients, of whom 42 (66%) were carrying CRLF2r and 24 (36%) were non-CRLF2r. Compared to non-Ph-like ALL (n=59), Ph-like ALL patients were younger (42 vs 36 years old, p=0.022), more frequently Hispanic (56% vs 83%, p=0.003), less frequently carried high-risk cytogenetics (39% vs 9%, p&lt;0.001), more frequently induced with pediatric-inspired regimens (25% vs 61%, p=0.003) and more likely required &gt;1 regimen to achieve their first complete remission (CR1; 30% vs 55%, p=0.025). However, we did not detect any significant difference between the two groups in disease status (CR1 vs. CD2/3; p=0.81) or minimal residual disease clearance at the time of HCT (negative vs. positive; p=0.17), donor type (match related/unrelated vs mismatch vs haplo vs cord blood; p=0.88), conditioning regimen intensity (myeloablative vs non-myeloablative/ reduced intensity; p=0.59), GVHD prophylaxis (tacrolimus/sirolimus-based vs PTCy-based; p=0.84), Karnofsky Performance Status (KPS; p=0.24) or HCT comorbidity index (0 vs 1-2 vs &gt;2; p=0.42). With the median follow-up of 3.2 years, we observed similar 3-years leukemia-free survival (LFS) (40% vs 47%; p=0.95), OS (44% vs 54%; p=0.96), relapse rate (33% vs 34%; p=0.96) and non-relapse mortality (NRM) (27% vs 19%; p=0.92) between non-Ph-like and Ph-like ALL patients, respectively. (Figure) In multivariable analysis, disease status at the time of HCT (HR=2.63, 95% CI: 1.57-4.41; p&lt;0.001), donor type (p=0.049) and KPS (HR=2.22, 95% CI: 1.05-4.69; p=0.038) influenced OS. LFS was significantly influenced by disease status (HR=2.35, 95% CI: 1.45-3.80); p&lt;0.001) and conditioning regimen intensity (HR=1.84, 95% CI: 1.11-3.04; p=0.017). Relapse rate was associated with disease status (HR=2.06, 95%CI: 1.11-3.84; p=0.23) and conditioning regimen intensity (HR=1.97, 95% CI: 1.03-3.75; p=0.40). Only KPS (HR=6.56, 95% CI: 2.48-17.36; P&lt;0.001) was associated with NRM. In conclusion, our data suggest that alloHCT consolidation results in favorable outcomes in adult patients with Ph-like ALL with comparable outcomes to non-Ph-like ALL. Our data support utilization of alloHCT for adults with Ph-like ALL in CR. Figure 1 Figure 1. Disclosures Al Malki: Neximmune: Consultancy; Rigel Pharma: Consultancy; Jazz Pharmaceuticals, Inc.: Consultancy; Hansa Biopharma: Consultancy; CareDx: Consultancy. Khaled: Omeros: Honoraria; Alexion: Honoraria, Speakers Bureau; Janssen: Current Employment; Astellas: Honoraria; Jazz: Honoraria. Ali: Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees. Aribi: Seagen: Consultancy. Mei: BMS: Research Funding; Epizyme: Research Funding; TG Therapeutics: Research Funding; EUSA: Honoraria; Janssen: Honoraria; Morphosys: Research Funding; Beigene: Research Funding. Koller: Novartis: Consultancy. Artz: Radiology Partners: Other: Spouse has equity interest in Radiology Partners, a private radiology physician practice. Stein: Amgen: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Stemline: Speakers Bureau. Marcucci: Abbvie: Other: Speaker and advisory scientific board meetings; Novartis: Other: Speaker and advisory scientific board meetings; Agios: Other: Speaker and advisory scientific board meetings. Forman: Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company; Allogene: Consultancy. Pullarkat: AbbVie, Amgen, Genentech, Jazz Pharmaceuticals, Novartis, Pfizer, and Servier: Membership on an entity's Board of Directors or advisory committees; Amgen, Dova, and Novartis: Consultancy, Honoraria.

Excellent Outcomes of the Second Allogeneic Hematopoietic Stem Cell Transplantation in Hematological Malignancies with Reduced Toxicity Conditioning and Donor Change

Introduction: High relapse rate and transplant-related mortality (TRM) are the major obstacles for the second allogeneic hematopoietic stem cell transplantation (allo-HSCT). Reduced-toxicity conditioning (RTC) can decrease TRM and healthier donor may provide stronger anti-leukemia and anti-infection effects. Objective:In current clinical study, the safety and efficacy of the second allo-HSCT with RTC and donor change were examined. Methods: Between April 2018 and June 2021, total 48 patients with hematological malignancies (B-ALL 26, T-ALL/LBL 4,AML16,MDS 2) who failed to the first allo-HSCT(relapsed 47, secondary rejection 1) and underwent the second allo-HSCT in our hospital were enrolled. The median age was 25(5-55) years old. Male to female was 25:23. Before the second allo-HSCT, 35 (72.9%) patients were in complete remission (CR) (minimal residual disease (MRD) negative in 28, MRD positive in 7), and 13 (27.1%) cases (B-ALL7,T-ALL/LBL2,AML3,MDS1) in non-remission(NR). The median interval between twoallo-HSCTs was 19.5 (8-77) months. For better donor selection, the functions of hematopoiesis and immune (subsets of lymphocyte, immune globulin,and granzyme and perforin of NK cell) as well as hematological and immunological hereditary predisposition gene variants for potential donors were tested. The types of the first allo-HSCT included haploidentical (n=33), unrelated (n=8), identical sibling (n=5), and unrelated cord blood (n=2). All donors were changed for the second allo-HSCT(haploidentical 35, unrelated 13)except one recipient no other donor available. RTC regimens were mainly total body irradiation(TBI)/fludarabine (FLU)-based(n=39) or busulfan (BU)/FLU-based (n=7).Two patients were with total marrow irradiation (TMI)/FLU-basedregimen. For TBI/FLU regimen, fractionated TBI (8Gy in 32, 10Gy in 7), cytarabine 1-2g/m 2 for 3 days,FLU 30mg/m 2 for 5 days, Me-CCNU 250mg/m 2 for 1 day, and ATG were used. For BU/FLU regimen, BU 0.8mg/kg q6h for 3 days, cytarabine 1-2g/m 2 for 3 days,FLU 30mg/m 2 for 5 days, Me-CCNU 250mg/m 2 for 1 day, and ATG were used. For TMI/FLU regimen, the same conditioning as TBI/FLU was used except fractionated TMI 10-12Gy instead of TBI. Decitabine (20mg/m 2, 3 days) or etoposide (200mg/m 2, 2 days) were administrated in some patients in NR or MRD positive. Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for graft-versus-host disease (GVHD) prophylaxis. Some patients received maintenance therapy post-transplant with targeted medicine based on their fusion genes or gene mutations. Results: ALL patients became full donor chimerism. The median time for neutrophil and platelet recovery was 15 (11-22) days and 16 (10-240) days. The incidences of grade II-IV acute GVHD (aGVHD) and chronic GVHD(cGVHD) were 18.8%, 47.5% (limited 25%, extensive 22.5%), respectively. The incidences of CMV and EBV reactivation were 31.3% and 6.3%. No severe hemorrhagic cystitis occurred. The median follow-up was 13(1-38) months. One-year disease-free survival (DFS) and overall survival (OS) of all patients were 68.7% (95% CI:0.511;0.811) and 78.9% (95% CI:0.62;0.889) . Nine patients died(relapse 7,GVHD and infection 2).The relapse rate was 22.9%.TRM was only 4.2%. NR before transplant and TP53 mutation were high risk for disease recurrence post-HSCT. Relapse rates were 53.8% vs. 11.4% in NR and CR patients, and 50% vs. 17.5% in the patients with or without TP53 mutation. Disease status before transplant was key impact factor for survival after the second allo-HSCT. One-year OS in CR and NR settings were81.4 % and 70%, respectively, p=0.13. One-year DFS in CR and NR settingswere79.6%, and 41.9%, respectively, p=0.005. No significant difference of DFS was seen in haploidentical and unrelated transplants(68.1% vs.71.8%, p=0.627). Conclusions: With our strategy of RTC regimens and donor change, excellent outcomes of the second allo-HSCT in hematological malignancies have been achieved. One-year DFS and OS are 68.7% and 78.9%. Both TRM and relapse rate are low (4.2%, 22.9%). The most important factor on prognosis of the second allo-HSCT is disease status before transplant but not donor type. TP53 mutation also has negative impact on DFS after the second allo-HSCT. Disclosures No relevant conflicts of interest to declare.

Treatment of Multiple Sclerosis With Teriflunomide. Multicenter Study of Real Clinical Practice in the Valencian Community-Spain

Introduction: We have different treatment alternatives for relapsing-remitting multiple sclerosis–RRMS–within the so-called platform drugs. It would be desirable to know the ideal drug for each patient. Real clinical practice studies provide us with data on drug efficacy in the medium and long term, safety beyond clinical trials, and can help us to know the patient profile appropriate for each therapy.Material and Methods: An observational multicenter study of real clinical practice in patients with RRMS who were treated with teriflunomide in the Valencian Community, since teriflunomide was authorized in Spain. The database created for this study collects retrospectively patients followed prospectively in the MS clinics.Objectives: To analyze the efficacy and safety of teriflunomide treatment in patients with RRMS under the conditions of real clinical practice, and to identify a patient profile responding to the treatment.Results: We obtained data from 340 patients who received at least one dose of 14 mg teriflunomide. The patients were 69.4% female to 30.6% male, had a mean age of 46.4 years, and a mean time of progression of MS of 11.5 years. The mean pre-teriflunomide relapse rate was 0.4 years, the mean EDSS scorewas 1.98, IgG Oligoclonal bands were present in the CSF of 66.2% of the patients, IgM Oligoclonal bands were present in 46.9%, and the mean number of gadolinium-enhancing lesions was 1.07 lesions per patient at the beginning of treatment. The average number of treatments previously received was 1.04, and 28.53% were naïve. After a follow-up of up to 4 years, a reduction in the annualized and cumulative annualized relapse rate was observed in the first year, in the second year, and in the third year, compared to the pre-treatment year. The EDSS scores were stabilized throughout the follow-up. Likewise, there was a reduction in gadolinium-enhancing lesions in the 1st and 2nd years compared to the pre-treatment period. Applying different generalized multiple linear regression models, we identified a profile of a responding patient to teriflunomide as a male without IgM oligoclonal bands in the CSF, a previous EDSS score of &lt;3, and more than 5 years duration of MS.

Pain as the evaluation criterion for bone metastasis radiosensitivity. Comparative efficacy of radiation therapy in patients with bone metastases of various primary tumors.

Purpose: Assessment of the comparative radiosensitivity of bone metastases of various nature and histogenesis. Material/methods: As part of a randomized study, 810 courses of 3D-conformal or IMRT / VIMAT radiotherapy were performed for bone metastases of various origins and localization with persistent pain syndrome. Radiotherapy protocol included hypofractionation regimes of 2, 3 or 4 fractions of 6,5 Gy with total dose of 13-26 Gy or standard fractionation regime with total dose of 46 Gy. Results: The overall effectiveness (сomplete and partial pain relief) of radiotherapy was 96.2%, complete response rate (CRR) – 56.2%, partial response rate – 40.0%. Pain relapse rate was 8.6%, on average after 9.5 months after irradiation. The independent predictors of the CRR were: the initial pain intensity [hazard ratio (RR): 0.48, confidence interval (CI): 0.40-0.58; p = 0.0001], dose/number of fractions (RR: 1.26, CI: 1.07-1.50; p = 0.0059) and primary tumor site (RR: 0.95, CI: 0.92-0,99; p = 0.0053). We constructed a scale of comparative radiosensitivity of bone metastases of various primary tumors, taking into account the complete response rate and the probability of surviving without pain relapse for 6, 12 and 24 months after radiotherapy. The radiosensitive group included metastases from breast and prostate cancer, melanoma, bladder and PNET (CRR 60% or more), and relatively radioresistant group - metastases from unknown origin, colon, stomach and kidney cancer (CRR 40% or less). Conclusion: More than 95% overall effectiveness of radiotherapy for bone metastases, with pain relapse rate of less than 10% of cases, allows us to consider widefield irradiation in doses of 19.5-26 Gy, in 3-4 fractions of 6.5 Gy, the preferred treatment for multifocal lesions. Dose escalation in patients with bone metastases of kidney, colon, lung cancer and metastases from unknown origin seems to be justified in the cases with a life expectancy of more than a year.

Monocyte to High-Density Lipoprotein Ratio: A Novel Predictive Marker of Disease Severity and Prognosis in Patients With Neuromyelitis Optica Spectrum Disorders

Background and Purpose: To investigate the association of monocyte to high-density lipoprotein ratio (MHR) with disease severity and prognosis in patients with neuromyelitis optica spectrum disorders (NMOSD).Methods: This retrospective study included 125 patients with NMOSD. Demographic and clinical parameters, including the MHR, were assessed. The initial Expanded Disability Status Scale (EDSS) score and relapse rate were used to evaluate disease severity and prognosis, respectively. Correlations between MHR and disease severity and relapse rate were analyzed. The predictive value of MHR for prognosis was evaluated using receiver operating characteristic (ROC) curve analysis.Results: Compared with the low MHR group, the initial EDSS score (median 4.5 vs. 5.5%, P = 0.025) and relapse rate (51.61 vs. 30.16%, P = 0.015) were significantly higher in the high MHR group. MHR was positively correlated with the initial EDSS score (r = 0.306, P = 0.001). Multivariate analysis showed that MHR was significantly associated with severity (odds ratio = 7.90, 95% confidence interval [CI] = 1.08–57.82, P = 0.041), and it was a significant predictor of disease prognosis (hazard ratio = 3.12, 95% CI = 1.02–9.53, P = 0.046). The median relapse interval of the high MHR group was 24.40 months. When the MHR was higher than 0.565, the risk of relapse was high [sensitivity, 33.3%; specificity, 91.9%; area under the ROC curve, 0.642 (95% CI = 0.54–0.74, P = 0.007)].Conclusion: MHR is a novel predictive marker of disease severity and prognosis in patients with NMOSD. Early monitoring and reduction of MHR may allow earlier intervention and improved prognosis.