Presence Of Relapses Research Articles

Abstract PO5-21-07: Mitomycin: its developmental role in the treatment of patients with BRCA - associated triple-negative early and locally advanced breast cancer

Abstract Rationale. BRCA-associated triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer with high sensitivity to chemotherapy, which leads to increased interest in the development of new strategies for neoadjuvant treatment of patients with a triple-negative tumor phenotype. The aim of the study is to determine the role of adding platinum to standard neoadjuvant systemic therapy in patients with primary BRCA-associated TNBC, to evaluate the effect of platinum preparations on relapse-free survival in patients of this category, to determine the role of adding mitomycin to platinum in patients with primary BRCA-associated TNBC. Materials and methods. The study included 80 patients diagnosed with primary BRCA - associated TNBC, divided into 3 groups according to the treatment. Each group was subdivided depending on the final pathomorphological result and the presence of relapses. Results. 80 patients with primary BRCA-associated TNBC were divided into 3 groups depending on the ongoing neoadjuvant chemotherapy (NACT). Group I included 48 (60%) patients who received the AC-T regimen, in group II — NAC according to the AC-TCarb regimen, 27 (33.75%) patients, in group III — NAC with mitomycin in combination with cisplatin, 5 (6.25%) of patients. A comparative analysis of the results of the frequency of achieving complete pathomorphological regression (pCR), depending on the addition of a platinum drug to standard NAC, showed the advantage of group II compared to group I (73.7% vs. 41.2%, respectively, p = 0.0433). Taking into account the ongoing NAC regimens, with a median follow-up of 20.7 months, patients of group I had a slightly higher risk of relapse compared to patients of group II (p = 0.099). Patients of group III demonstrated the achievement of pCR in 66.6% of cases (2/3) during the full course of NAC, 2 patients of group III did not complete the planned course of NAC for medical reasons, due to the development of a pronounced nephrotoxic effect. During the observation period of group III, no cases of relapse were recorded. Conclusions.The addition of platinum drugs to the standard anthracycline/taxane NAPCT regimen in patients with primary BRCA-associated TNBC, results in a higher pCR rate, which entails a reduced risk of disease recurrence.The use of the new NAC regimen with mitomycin in combination with platinum compounds has promising results in patients with this oncopathology, which deserves a more detailed clinical evaluation.Performinga full course of planned NAC has a positive tendency in achieving pCR in patients of this category. Keywords: BRCA1/2 mutation; triple negative breast cancer; platinum preparations; mitomycin; neoadjuvant chemotherapy. Citation Format: Petr Krivorotko, Evgeniy Imyanitov, Diana Enaldieva, Elena Zhiltsova, Roman Donskih, Anna Sokolenko, Laysan Shaikhelislamova, Larisa Gigolaeva, Tengiz Tabagua, Alexander Komyakhov, Kirill Nikolaev, Konstantin Zernov, Sergey Yerechshenko, Roman Pesotsky, Nikolay Amirov, Alexander Emelyanov, Viktoria Mortada, Yana Bondarchuk, Vladislav Semiglazov. Mitomycin: its developmental role in the treatment of patients with BRCA - associated triple-negative early and locally advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-21-07.

Blood sphingolipid as a novel biomarker in patients with neuromyelitis optica spectrum disorder

BackgroundSphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). MethodsWe measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses). ResultsWe investigated 81 patients and 10 controls. PLS-DA models utilizing sphingolipids successfully differentiated patients with EDSS > 3.0, but failed to identify the presence of disease and relapses. Ceramide-C14—a significant contributor to differentiating EDSS > 3.0—positively correlated with EDSS, while its levels were independent of age and the presence of relapses. This characteristic was unique from those of sNfL and sGFAP, which were affected by age and relapses as well as EDSS. ConclusionPlasma sphingolipids may be useful NMOSD biomarkers for disability with distinct characteristics compared to sNfL and sGFAP.

Neutrophil/lymphocyte and monocyte/lymphocyte indexes as potential predictors of relapse at 1 year after diagnosis of pediatric multiple sclerosis: a single-center, exploratory and proof-of-concept study.

Early identification of patients with a more unfavorable outcome in Multiple Sclerosis (MS) is crucial to optimize individualized treatment. Neutrophil-lymphocyte index (NLI) and monocyte-lymphocyte index (MLI) have been considered as potential biomarkers for disease prognosis. Our study aims to investigate the usefulness of NLI and MLI as predictors of relapse, disability progression, and lesion accumulation on magnetic resonance imaging (MRI) 1 year after diagnosis and treatment initiation, in pediatric-onset MS. A retrospective single-center study was conducted, including patients with diagnosis of MS established in pediatric age (<18 years old), at least 1-year of follow-up, and a complete blood count (CBC) performed at diagnosis. We collected the nearest-to-diagnosis NLI and MLI, as well as clinical and imaging variables, at diagnosis and 12 months later. Our cohort was further dichotomized into two groups, based on the presence of relapses. Statistical significance was considered for p < 0.05. Eighteen patients (n = 18) were included. The relapsing group had higher mean, minimum, and maximum values for both NLI (5.17 ± 5.85, range: 1.57-11.92) and MLI (0.35 ± 0.22, range: 0.19-0.59), compared to the non-relapsing group (2.19 ± 1.63, range: 1.12-7.32 for NLI, and 0.24 ± 0.09, range: 0.14-0.44 for MLI). A higher percentage of patients in the relapsing group had increased NLI (>1.89, 66.7%) and MLI (>0.21, 66.7%) values than those in the non-relapsing group (46.7%). Patients who presented new T2-hyperintense lesions on MRI after 1 year of follow-up also had higher mean, minimum, and maximum values of both biomarkers. Patients who did not achieve No Evidence of Disease Activity-3 (NEDA-3) state exhibited higher values for both ratios. However, in our sample, no statistically significant correlations were found between MLI and NLI values and the clinical and imaging variables considered. The ease of obtaining NLI and MLI from routine blood tests renders them useful biomarkers as a screening tool in longitudinal follow-up. Our study was based on a very small sample size, but it allowed us to verify the feasibility of the protocol used. It is intended to involve other centers in the next phase of this work, testing the possible usefulness of the indices under analysis on a larger sample.

Idiopathic autoimmune encephalitis with a recurrent course. A case report

We presented a clinical case of idiopathic autoimmune brainstem encephalitis in a 12-year-old female patient. At the onset of the disease, which developed after a respiratory infection, the clinical picture was accompanied by oculomotor and bulbar syndromes. The diagnosis of Bickerstaff brainstem encephalitis was made based on clinical diagnostic criteria and the positive effect of the course of intravenous immunoglobulin therapy. During 3 years of follow-up, there were periods of relapse of the disease, during which symptoms not typical for Bickerstaff stem encephalitis appeared. Against the background of long-term immunosuppressive therapy, there was a long-term remission of about 2 years. The clinical picture, the presence of relapses, the data of additional methods forced to reconsider the diagnosis in favor of idiopathic autoimmune brainstem encephalitis.

Natalizumab continuation versus switching to ocrelizumab after PML risk stratification in RRMS patients: a natural experiment

BackgroundNatalizumab (NTZ) and ocrelizumab (OCR) can be used for the treatment of relapsing–remitting multiple sclerosis (RRMS). In patients treated with NTZ, screening for JC virus (JCV) is mandatory, and a positive serology usually requires a change in treatment after 2 years. In this study, JCV serology was used as a natural experiment to pseudo-randomize patients into NTZ continuation or OCR.MethodsAn observational analysis of patients who had received NTZ for at least 2 years and were either changed to OCR or maintained on NTZ, depending on JCV serology status, was performed. A stratification moment (STRm) was established when patients were pseudo-randomized to either arm (NTZ continuation if JCV negativity, or change to OCR if JCV positivity). Primary endpoints include time to first relapse and presence of relapses after STRm and OCR initiation. Secondary endpoints include clinical and radiological outcomes after 1 year.ResultsOf the 67 patients included, 40 continued on NTZ (60%) and 27 were changed to OCR (40%). Baseline characteristics were similar. Time to first relapse was not significantly different. Ten patients in the JCV + OCR arm presented a relapse after STRm (37%), four during the washout period, and 13 patients in the JCV-NTZ arm (32.5%, p = 0.701). No differences in secondary endpoints were detected in the first year after STRm.ConclusionsThe JCV status can be used as a natural experiment to compare treatment arms with a low selection bias. In our study, switching to OCR versus NTZ continuation led to similar disease activity outcomes.

МІНІІНВАЗИВНА ТОРАКОПЛАСТИКА ПРИ ХІРУРГІЧНОМУ ЛІКУВАННІ ДЕСТРУКТИВНОГО ТУБЕРКУЛЬОЗУ ЛЕГЕНЬ

Aim: to evaluate results of application of the developed technique of minimally invasive extrapleural thoracoplasty in the surgical treatment of patients with destructive pulmonary tuberculosis. Object and methods. Minimally invasive thoracoplasty was performed in 15 patients (study group): men made up 100 %, in the age range from 26 to 58 years. Chronic forms of pulmonary tuberculosis were diagnosed in 10 (66.6 %) patients, newly diagnosed tuberculosis in 5 (33.4 %). Multidrugresistant tuberculosis was observed in 78 % of patients. Bacterial excretion was observed in 86 % of patients. The size of the cavity in the lung did not exceed 6 cm. All patients in the pre- and postoperative periods received chemotherapy regimens based on the prescription of the CMAC / CRTB treatment regimen. The following effectiveness criteria were assessed: cessation of bacterial excretion 1 month after surgery (negative Bactec culture); closure of the destructive cavity confirmed on chest CT scan, the number of postoperative complications and the presence of relapses in the postoperative period. A new method of minimally invasive thoracoplasty was developed to improve the method of collapse-surgical treatment of patients with destructive pulmonary tuberculosis. It uses a resection of small segments of ribs, both in length and in number, extrapleural apicolysis and mediastinal pneumolysis, fixation of the lowered apex of the lung with polypropylene mesh, sealing the created extrapleural cavity with collagen to achieve adequate collapse of the lung in the cavernous zone and accelerate reparative pericavitary processes. The results. 15 patients were operated on according to this technique. Postoperative complications were observed in 1 (6.6 %) patient. Cessation of bacterial excretion after 1 month of treatment was registered in 100 % of patients, closure of the cavity after 2 months of treatment was achieved in 14 (93.3 %) patients. Key words: minimally invasive thoracoplasty, destructive pulmonary tuberculosis, polypropylene mesh, collagen plates.

Level of adherence to acne treatment and associated factors in patients with acne in Yaoundé, Cameroon (sub-Saharan Africa)

Background: Acne is a chronic inflammatory disease of the pilosebaceous follicle. The aim of this study was to assess the level of adherence to acne treatment and to identify factors associated with adherence to therapy in patients with acne. Materials and Methods: This was a descriptive, analytical, cross-sectional study conducted from January to April 2017 in three hospitals in Yaoundé. We included patients followed for acne for at least one month. The sampling was consecutive and exhaustive. Adherence to treatment was assessed according to the Morisky score. Data was analyzed with Microsoft Excel 2013 and the SPSS software, version 23. We employed the ANOVA test to find associations between the different variables. p values below 0.05 were considered statistically significant. Results: A total of 113 patients were selected, with a mean age of 26.0 ? 6.4 years. The mean Morisky score was 5.6 ? 1.9. Adherence to treatment was low, medium, and high in 58 (51%), 31 (28%), and 24 (21%) patients, respectively. The factors associated with low adherence were the presence of relapses, a psychological history, the number of previous treatments above two, and the duration of treatment above three months. Conclusion: Adherence to acne treatment was low in over half of the patients. In our context, the presence of relapse, a psychological history, the number of previous treatments above two, and the duration of treatment above three months were associated with low adherence to therapy.

043 Efficacy of siponimod in secondary progressive multiple sclerosis with active disease: EXPAND study subgroup analysis

BackgroundSiponimod, a selective sphingosine 1-phosphate receptor modulator, demonstrated clini- cally relevant effects in a typical secondary progressive multiple sclerosis (SPMS) population in the Phase 3 EXPAND study, with 21% and 26% reductions in 3- and 6-month confirmed disability progression (CDP) versus placebo.MethodsPost hoc subgroup analysis was performed in patients with active disease (defined as the presence of relapses in 2 years before screening and/or ≥1 T1 gadolinium-enhancing [Gd ] lesion at baseline) to assess the efficacy of siponimod 2mg versus placebo in this population.ResultsThis analysis included 779 SPMS patients with active disease (siponimod [n=516], placebo [n=263]). The proportion of patients with relapse in the 2 years prior to study was 76% and with Gd lesions at baseline 45%. Siponimod significantly reduced 3-month CDP risk by 31% (HR [95% CI]: 0.69 [0.53, 0.91]; p=0.0094) and 6-month CDP risk by 37% (HR [95% CI]: 0.63 [0.47, 0.86], p=0.0040) versus placebo. Reductions in risk of 6 month SDMT worsening, ARR, and MRI endpoints were also seen.ConclusionsIn this subgroup of active SPMS patients from EXPAND, benefits on disability progression were more pronounced with clinically relevant effects across disability progression, cognitive processing speed, and MRI inflammatory disease activity.g.giovannoni@qmul.ac.uk

Health-related quality of life in neuromyelitis optica spectrum disorder patients in an Argentinean cohort

BackgroundWe aimed to describe the health-related quality of life (HRQoL) in patients with neuromyelitis optica spectrum disorders (NMOSD), to compare HRQoL between NMOSD patients, multiple sclerosis (MS), and healthy controls (HC) and to study the associations between HRQoL and the clinical variables of the disease. MethodsA cross-sectional study was carried out. Patients with NMOSD seropositive, MS, and HC were enrolled and age-matched. The HRQoL was studied using the Argentinean validation of the SF-36 health questionnaire. Demographic and clinical characteristics were analyzed, as well as the EDSS and the total scores and subscales of the SF-36. Results243 individuals were included (NMOSD= 53, MS =100, and HC =90). The mean EDSS was 3.06 ± 2.01 in NMOSD and 2.67 ± 1.83 in MS with a mean of disease duration of 6.2 ± 4.4 and 6.3 ± 5.3 years, respectively. Significant statistical differences were observed in the total SF-36 score between both NMOSD and MS vs. HC (p < 0.01), but no differences were found when the total SF-36 score was compared between NMOSD vs. MS. Overall, NMOSD patients scored significantly lower in the total SF-36 and subscale scores compared to HC (p< 0.05). NMOSD patients also showed significant differences in bodily pain (58.8 ± 29.8 vs 75.1 ± 25.1, p < 0.01) and general health (44.4 ± 20.9 vs.31.9 ± 23.1, p < 0.01) when compared with MS, but no differences were found after comparing the rest of the subscales. We found that higher EDSS scores (β -1.28 p = 0.03) and disease duration (β 0.8, p = 0.02) were significantly associated to lower (worse) general health (dependent variable) score in NMOSD patients after having applied multiple linear regression analysis. Additionally, we observed that higher EDSS scores (β -10.2 p = 0.008) and the presence of relapses in the previous year (β -28.9, p = 0.02) were significantly associated to lower (worse) physical functioning (dependent variable) score. ConclusionPain seems to be a significant undertreated symptom in NMOSD patients that strongly impact on HRQoL. Patient-reported HRQoL scales scores provide comprehensive additional prognostic information beyond physical disability score.

An Abnormally High Neutrophil-to-Lymphocyte Ratio Is Not an Independent Outcome Predictor in AQP4-IgG-Positive NMOSD.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) has been investigated in many autoimmune conditions as a biomarker of inflammation and/or disease activity. The role of NLR in AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD) is far from clear. In this study, NLR was evaluated in patients with AQP4-IgG-positive NMOSD at disease onset and its prognostic impact was subsequently assessed.MethodsIn this multicenter study, we retrospectively included all recent/newly diagnosed treatment-naïve patients with AQP4-IgG-positive NMOSD (n=90) from three different countries in Latin America (LATAM): Argentina, Ecuador, and Mexico. NLR was compared between AQP4-IgG-positive NMOSD and healthy controls (HC, n = 365). Demographic, clinical, paraclinical (including imaging), and prognostic data at 12 and 24 months were also evaluated. Multivariate regression analysis was used to describe and identify independent associations between the log-transformed NLR and clinical (relapses and EDSS) and imaging (new/enlarging and/or contrast-enhancing MRI lesions) outcomes.ResultsNLR was higher in NMOSD patients during the first attack compared with HC (2.9 ± 1.6 vs 1.8 ± 0.6; p<0.0001). Regardless of immunosuppressant’s initiation at disease onset, NLR remained higher in NMOSD patients at 12 (2.8 ± 1.3; p<0.0001) and 24 (3.1 ± 1.6; p<0.0001) months. No association was found at 12 and 24 months between the log-transformed NLR and the presence of relapses, new/enlarging and/or contrast-enhancing MRI lesions, and/or physical disability.ConclusionsIn this cohort of LATAM patients with AQP4-IgG-positive NMOSD, NLR was abnormally high in attacks but also during follow-up. However, a high NLR was not an independent predictor of clinical or imaging outcomes in our models.

VULVOVAGINAL CANDIDIASIS IN COMBINATION WITH BACTERIAL VAGINOSIS IN WOMEN OF REPRODUCTIVE AGE: FEATURES OF PATHOGENESIS AND TREATMENT

The aim. Reducing the recurrence of vulvovaginal candidiasis (VVC) in combination with bacterial vaginosis (BV) in women of reproductive age by studying the pathogenesis and improving the algorithm of treatment and prevention measures.&#x0D; Materials and methods. During the study, 150 women of reproductive age who had the same clinical manifestations of VVC and BV were selected and divided into 3 groups of 50 women: Group I was treated with an antimicrobial combination drug (miconazole with topical metronidazole), group II – the same drug in combination with probiotic (lactobacilli) in candles, group III – according to the algorithm improved by the authors. In addition, a control group was formed, which included healthy women of reproductive age.&#x0D; To establish the pathogenesis of VVC in combination with BV in the studied women, the concentration of cytokines and adhesion molecules in the blood before and after treatment was determined and compared with the control group.&#x0D; The clinical effect of different treatments was assessed at 3, 7, 10, 14 days, and the presence of relapses – 1, 3, 6 months after treatment.&#x0D; Results. The occurrence of a combination of VVC and BV in women of reproductive age is accompanied by a significant increase in the level of intercellular adhesion molecules (ICAM-1) and vascular cell adhesion molecules (VCAM-1) along with a statistically significant increase in proinflammatory cytokines (interleukin-6) (IL-6), interleukin-8 (IL-8)) and tumor necrosis factor (TNF) - TNF-α. As a result of the application of the algorithm improved by the authors, higher clinical efficiency and the ability to avoid recurrence of VVC in combination with BV in women of reproductive age were obtained.&#x0D; Conclusions. The authors' substantiated improvement of the algorithm of VVC treatment in combination with BV in women of reproductive age makes it possible to reduce the frequency of their recurrence and restore the biocenosis of the vagina to normal. In the case of this pathology there is an increase in the level of pro-inflammatory cytokines (IL-6, IL-8), TNF-α and ICAM-1 and VCAM-1.

Опыт использования лоскута P. Castelnuovo в пластике послеоперационных перфораций перегородки носа

Postoperative nasal septum perforation (PNSP) is a complication of nasal septum (NS) surgery with an incidence of 1–8%. The effectiveness of surgical treatment ranges from 52 to 92%. In world practice, Castelnuovo operation is actively used, while the effectiveness of this technique in the treatment of PNSP requires a comprehensive study. Objectives: To assess the effectiveness of the method of closing the PNSP with a Castelnuovo flap. Materials and methods: 26 patients with PNSP were operated on. The number of patients depending on the area (S) of the PNSP: S &lt;1 cm2 – 2, S 1–2 cm2 – 21, S &gt; 2 cm2 – 3. In the postoperative period, cytological examination of smears from the NS surface was carried out (3rd, 6th, 10th, 15th, 20th days), questionnaire survey NOSE and assessment of mucociliary transport of the mucous membrane (MM) of the nasal cavity (10th, 15th, 20th, 25th and 30th, 40th 60th day), the presence of relapses of PNSP within 1 year were performed. Results: pronounced leukocyte infiltration and bacterial contamination of the wound were revealed up to 10 days, reparative processes were not expressed until 15 days. The indicators of mucociliary transport were brought back to normal by the 30th day (21,25 ± 1,90 minutes), the results of the NOSE questionnaire by the 60th day were 22.12 points, which corresponded to the zone of comfortable breathing. In all 26 patients, intraoperatively complete closure of the PNSP was performed. There were 7 recurrences of PNSP: 3 in the interval of 16–30 days, 2 – from 31 to 60 days, 1 – from 61 to 90 days, 1 – from 4 to 6 months. Synechiae between NS and inferior turbinate was found in 11,5%. The efficiency of Castelnuovo flap closure technique of PNSP was 73%. Conclusions: The results indicate a pronounced inflammation in the flap and NS tissues in the postoperative period and a change in the physiological course of the wound process in favor of healing by secondary intention.

High serum neurofilament associates with diffuse white matter damage in MS.

ObjectiveTo evaluate to which extent serum neurofilament light chain (NfL) increase is related to diffusion tensor imaging–MRI measurable diffuse normal-appearing white matter (NAWM) damage in MS.MethodsSeventy-nine patients with MS and 10 healthy controls underwent MRI including diffusion tensor sequences and serum NfL determination by single molecule array (Simoa). Fractional anisotropy and mean, axial, and radial diffusivities were calculated within the whole and segmented (frontal, parietal, temporal, occipital, cingulate, and deep) NAWM. Spearman correlations and multiple regression models were used to assess the associations between diffusion tensor imaging, volumetric MRI data, and NfL.ResultsElevated NfL correlated with decreased fractional anisotropy and increased mean, axial, and radial diffusivities in the entire and segmented NAWM (for entire NAWM ρ = −0.49, p = 0.005; ρ = 0.49, p = 0.005; ρ = 0.43, p = 0.018; and ρ = 0.48, p = 0.006, respectively). A multiple regression model examining the effect of diffusion tensor indices on NfL showed significant associations when adjusted for sex, age, disease type, the expanded disability status scale, treatment, and presence of relapses. In the same model, T2 lesion volume was similarly associated with NfL.ConclusionsOur findings suggest that elevated serum NfL in MS results from neuroaxonal damage both within the NAWM and focal T2 lesions. This pathologic heterogeneity ought to be taken into account when interpreting NfL findings at the individual patient level.

Immunohistochemical evaluation of surfactant-associated protein in fibrosis-cavernous pulmonary tuberculosis

Background. Despite the progress and development of scientific directions in various fields of medicine, the problem of tuberculosis and its morphological manifestations remains relevant and is not fully disclosed due to complex pathogenesis, the presence of various clinical forms, therapeutic pathomorphosis, torpid to therapy, the presence of relapses. It is known that a surfactant system occupies a special place in the system of local lung protection.Aim. To study the condition of surfactant-assotiated protein A in the foci of specific destruction and in the surrounding intact lung tissue to assess its functional status, degree of respiratory failure and possible dissemination of tuberculous inflammation.Material and Metods. An analysis of 163 lung fragments of the dead or operated on for cavernous pulmonary tuberculosis with active bacterial excretion of 89 fragments and with clinical abacilation – 74 was carried out. Results A morphological study revealed stereotypical dynamic depression of surfactant-associated protein A in all the samples studied, both in the areas of cavernous destruction and pericavernouse zone, and in intact lung tissue. The maximum intensivity of the immunohistochemical expression of this surfactant protein was recorded in the alveolar macrophages, which indicated intensive recycling and utilization of the components of the surfactant.Conclusion. Minimizing the production of surfactant components and its active utilization in intact lung tissue leads to a collapse of the alveoli with subsequent progression of respiratory failure.

Correlation of serum endothelin-1 with relapses of surgical treatment of diabetic maculopathy in type 2 diabetes mellitus

Introduction. In type 2 diabetes mellitus (T2DM), a cascade of pathological reactions unfolds in the vas­­cular endothelium, which, in turn, is included in the pathogenesis mechanisms and causes the develop­­ment of complications. The main marker of endothelial function is its hormone — endothelin-1 (ET1). The aim of the study was to establish the relation­ship between serum ET1 and relapses in the surgical treatment of diabetic maculopathy (DMP) using various options for vitreoretinal interventions in patients with TD2M. Material and methods. We observed 313 patients T2DM (313 eyes) with DMP and initial (group 1; n = 40), moderate or severe non-proliferative (NPDR; group 2; n = 92) and proliferative diabetic retinopathy (PDR; group 3; n = 181). The severity of retinopathy and DMP was determined in accordance with the recom­men­dations of the American Academy of Ophthalmology (2002). In this study, patients underwent four types of surgical interventions: 78 patients (78 eyes) underwent a three-port closed subtotal vitrectomy; 85 patients (85 eyes) — closed subtotal vitrectomy with peeling of the retina inner border membrane; 81 patients (81 eyes) — closed subtotal vitrectomy with peeling of the retina inner border membrane in combination with panretinal laser coagulation; 69 patients (69 eyes) — closed subtotal vitrectomy with peeling of the retina inner border membrane and panretinal laser coagu­lation in combination with cataract phacoemulsifica­­tion. In pa­­tients before surgery, serum ET1 levels were determined by enzyme-linked immunosorbent assay. The control group consisted of 95 people. For statistical processing of the obtained data, Statistica 10 software (StatSoft, Inc., USA) was used. Results and discussion. In patients with DMP serum ET1 level was many times higher: in group 1 it exceeded the control by 2.9 times, in group 2 — by 3.7 times and in group 3 — by 4.6 times (p < 0.001). The initial ET1 level did not differ with different methods of surgical intervention; there was also no statistical difference between the serum ET1 in each group with different treatment methods (p > 0.5). Serum ET1 level was higher in patients of group 1 with the presence of relapses, compared with patients of the same group who didn’t have relapses (by 1.4 times; p < 0.001). In patients of the remaining groups, there was no such difference (p > 0.2), thus, the level of ET1 was important for the formation of relapses only for patients with initial NPDD. Serum ET1 level was also higher in pa­­tients who had early persistent relapses (p < 0.001), which related to moderate and severe NDPR and PDR. Conclusion. The results showed a correlation bet­­ween the serum level of ET1 and the occurrence of early sustained relapses in the surgical treatment of DMP in patients with T2DM.

Th1Th17CM Lymphocyte Subpopulation as a Predictive Biomarker of Disease Activity in Multiple Sclerosis Patients under Dimethyl Fumarate or Fingolimod Treatment.

Peripheral blood biomarkers able to predict disease activity in multiple sclerosis (MS) patients have not been identified yet. Here, we analyzed the immune phenotype of T lymphocyte subpopulations in peripheral blood samples from 66 RRMS patients under DMF (n = 22) or fingolimod (n = 44) treatment, by flow cytometry. A correlation study between the percentage and absolute cell number of each lymphocyte subpopulation with the presence of relapses or new MRI lesions during 12-month follow-up was performed. Patients who had undergone relapses showed at baseline higher percentage of Th1CM cells (relapsed: 11.60 ± 4.17%vs. nonrelapsed: 9.25 ± 3.17%, p < 0.05) and Th1Th17CM cells (relapsed: 15.65 ± 6.15%vs. nonrelapsed: 10.14 ± 4.05%, p < 0.01) before initiating DMF or fingolimod treatment. Kaplan-Meier analysis revealed that patients with Th1Th17CM (CD4+CCR7+CD45RA−CCR6+CXCR3+) cells > 11.48% had a 50% relapse-free survival compared to patients with Th1Th17CMcells < 11.48% whose relapse-free survival was 88% (p = 0.013, log-rank test). Additionally, a high percentage of Th1Th17CM cells was also found in patients with MRI activity (MRI activity: 14.02 ± 5.87%vs. no MRI activity: 9.82 ± 4.06%, p < 0.01). Our results suggest that the percentage of Th1Th17CM lymphocytes at baseline is a predictive biomarker of activity during the first 12 months of treatment, regardless of the treatment.

Developmental trajectories of gambling severity after cognitive-behavioral therapy

AimsTo estimate trajectories of the gambling disorder (GD) severity for 12 months following a manualized cognitive-behavior-therapy (CBT) program, and to identify the main variables associated with each trajectory. MethodsLatent Class Growth Analysis examined the longitudinal changes of n = 603 treatment-seeking patients with GD. ResultsFive separate empirical trajectories were identified: T1 (n = 383, 63.5%) was characterized by the most highest baseline gambling severity levels and positive progress to recovery during the follow-up period; T2 (n = 154, 25.5%) featured participants with high baseline gambling severity and good progress to recovery; T3 (n = 30, 5.0%) was made up of patients with high gambling baseline severity and slow progress to recovery; T4 (n = 13, 2.2%) and T5 (n = 23, 3.8%) contained participants with high baseline gambling severity and moderate (T4) and poor (T5) progress in GD severity during the follow-up. Psychopathological state and personality traits discriminated between trajectories. Poor compliance with the therapy guidelines and the presence of relapses also differed between the trajectories. ConclusionsOur findings show that patients seeking treatment for GD are heterogeneous and that trends in progress following treatment can be identified considering sociodemographic features, psychopathological state and personality traits. These results could be useful in developing more efficient interventions for GD patients.

Targeting molecular pathways in cancer stem cells by natural bioactive compounds.

Cancer Stem Cells (CSCs) or Tumor-Initiating Cells (TICs) are a small sub-population of cells within the tumor, able to give chemio- and radio-resistance and cause the onset of metastasis and the presence of relapses; for these reasons, they are recently becoming a potential target for anticancer therapy. One of the main characteristics of these cells is the self-renewal through the capability of modulating different molecular signalling pathways, including Wnt/β-Catenin, Sonic Hedgehog and Notch pathways. Natural bioactive compounds such as resveratrol, epigallocatechin, curcumin, quercetin, ellagic acid, anthocyanins and other compounds and extracts can have a direct or indirect effect on these molecular pathways, decreasing the pathological activities of CSCs. This review aims to report and summarize the in vitro and in vivo studies about the preventive, therapeutic and chemosensitizing effects of these natural bioactive compounds on CSCs deriving from different types of tumors.

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting

BackgroundThough the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. MethodsTOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. ResultsOf the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). ConclusionsIn TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance.

La consejería de enfermería disminuye la sintomatología y recaídas en pacientes pediátricos con rinitis alérgica

BackgroundAllergic rhinitis (AR) is considered to be a public health problem, therefore it is essential to test health education strategies such as nursing counseling (NC) aimed at population groups such as children with allergic rhinitis and their tutors. This study aimed to measure the health benefits of children with this disease for a year. MethodsLongitudinal, randomized, comparative study with a sample of 100 pediatric patients of both sexes, aged 6 to 12 years, with diagnosis of allergic rhinitis, with counseling (study group) and without counseling (control group). In both groups, an informed consent letter signed by both tutors was obtained, in addition to knowledge and assessment papers; the latter included a scale of symptomatology and Morisky Green (adherence to treatment). The children in the study group received intervention based on personalized education, didactic material, support of the multidisciplinary group if necessary (doctor, dermatologist and psychologist). The control group received usual care. In both groups, telephone follow-up was performed, which allowed the number of relapses to be identified in one year. ResultsThe Wilcoxon rank-sum test (Mann-Whitney) was used to compare the results; the presence of relapses in the control group was statistically significant compared to the study group. ConclusionsIt was found that the infant population that receives NC, has as a better benefit the control of the symptomatology and decrease of relapses per year.