Signs Of Disease Activity Research Articles

Outcome Measures in Adult Vulvar Lichen Sclerosus: A Case Series of Women Diagnosed as Juveniles.

Studies on the consequences of juvenile vulvar lichen sclerosus (JVLS) in adulthood are limited. A number of measuring tools are available for analyzing adult vulvar lichen sclerosus (VLS), but these have not been applied in studies on JVLS. The aim is to study physical findings, quality of life, sexual well-being, and self-image in adult women with a history of juvenile VLS. Adult women with a biopsy proven history of JVLS were recruited to be examined and surveyed using available standardized measurement tools. This took place in an outpatient setting by physicians who were not involved in the treatment of participants. Twenty-seven women (median age 29 years) with a history of JVLS and median time since biopsy of 19.5 years were recruited. Of these women, 59% currently had symptoms, 63% had signs of active disease, and 85% had moderate to severe architectural changes. Despite these residual signs, vulvar specific-quality of life and vulvar self-image scored favorably while generic health-related quality of life was somewhat effected. JVLS has consequences in adulthood involving physical findings and vulvar quality of life. The use of standardized outcome measures for clinical practice and research purposes facilitates a better understanding of the sequelae to JVLS.

Personalised exercise rehabilitation in cancer survivorship: the percs triage and referral system study protocol

BackgroundTo effectively embed exercise rehabilitation in cancer survivorship care, a co-ordinated system of acute and community exercise rehabilitation services, forming a stepped model of care, is recommended. Patients can be directed to the exercise rehabilitation service which best meets their needs through a system of assessment, triage and referral. Triage and referral systems are not yet widely applied in cancer survivorship practice and need to be evaluated in real-world contexts. The PERCS (Personalised Exercise Rehabilitation in Cancer Survivorship) study aims to evaluate the real-world application of an exercise rehabilitation triage and referral system in cancer survivors treated during the COVID-19 pandemic. Secondary aims are to evaluate change in physical and psychosocial outcomes, and to qualitatively evaluate the impact of the system and patient experiences, at three months after application of the triage and referral system.MethodsThis study will assess the implementation of an exercise rehabilitation triage and referral system within the context of a physiotherapy-led cancer rehabilitation clinic for cancer survivors who received cancer treatment during the COVID-19 pandemic. The PERCS triage and referral system supports decision making in exercise rehabilitation referral by recommending one of three pathways: independent exercise; fitness professional referral; or health professional referral. Up to 100 adult cancer survivors treated during the COVID-19 pandemic who have completed treatment and have no signs of active disease will be recruited. We will assess participants’ physical and psychosocial wellbeing and evaluate whether medical clearance for exercise is needed. Participants will then be triaged to a referral pathway and an exercise recommendation will be collaboratively decided. Reassessment will be after 12 weeks. Primary outcomes are implementation-related, guided by the RE-AIM framework. Secondary outcomes include physical function, psychosocial wellbeing and exercise levels. Qualitative analysis of semi-structured interviews guided by the Consolidated Framework for Implementation Research (CFIR) will provide insights on implementation and system impact.DiscussionThe PERCS study will investigate the real-world application of a cancer rehabilitation triage and referral system. This will provide proof of concept evidence for this triage approach and important insights on the implementation of a triage system in a specialist cancer centre.Trial registrationThis study is registered on ClinicalTrials.gov, registration number: NCT05615285, date registered: 21st October 2022.

How Future Pharmacologic Therapies for Celiac Disease Will Complement the Gluten-Free Diet

The only proven treatment for celiac disease is adherence to a strict, lifelong, gluten free diet. However, complete dietary gluten avoidance is challenging and a substantial number of patients do not respond fully, clinically or histologically, despite their best efforts. As celiac disease is common and its central pathophysiology is well elucidated, it has become attractive for drug development to address the limitations of dietary treatment. Most efforts address non-responsive celiac disease, defined as continued symptoms and/or signs of disease activity despite a gluten free diet, including the more severe forms of refractory celiac disease type 1 and 2. An increasing spectrum of therapeutic approaches target defined mechanisms in celiac disease pathogenesis, and some currently advance to phase 2-3 clinical studies. We discuss these approaches in terms of potential efficiency, practicability, safety and need as defined by patients, regulatory authorities, health care providers and payors.

Flashy lungs and sarcoidosis: not always a sign of disease activity.

This is the case of a 68-year-old man with known cardiac sarcoidosis undergoing treatment with methotrexate who presented with new onset of dyspnea and lipothymia. FDG-PET/CT revealed pathological uptake within lung parenchyma which resolved following discontinuation of methotrexate, compatible with methotrexate-induced pneumonitis. This is the first case of methotrexate-induced pneumonitis documented by FDG-PET/CT.

INDOLENT SYSTEMIC MASTOCYTOSIS MASQUERADING AS CHRONIC ANEMIA IN ULCERATIVE COLITIS: A CASE STUDY

Abstract BACKGROUND Anemia is a frequent systemic/extra-intestinal manifestation of inflammatory bowel disease (IBD). It has a complex multifactorial etiology which suppresses erythropoiesis due to pro-inflammatory mediators, myelosuppression, iron and micronutrient deficiency. It significantly impacts quality of life (QoL) and increases hospitalizations, length of hospital stays and mortality rates. It Is commonly thought to arise as a consequence of IBD or it’s related therapy. Current strategies are aimed at correction of anemia with low priority towards identifying a specific cause. Here, we represent a case of UC with chronic anemia secondary to systemic mastocytosis (SM). CASE A 41 y/o female with UC presents to the outpatient clinic with complaints of fatigue. Further questioning revealed a baseline of 1-2 formed bowel movements per day. She did not report any hematochezia or weight loss. She was managed on 300 mg of vedolizumab every 4 weeks. Prior failure to medications includes anti-tumor necrosis factor inhibitors and tofacitinib. Labs were consistent with albumin 4.5 mg/dL and CRP < 1 mg/dL. Iron studies revealed low iron, TIBC and ferritin levels. Fecal calprotectin measurements were not available due to patient non-compliance. Patient (Pt) was thought to have experienced a UC flare and colonoscopy was recommended. Colonoscopy was unrevealing with no sign of active disease on examination (Mayo Endo 0). Pt was referred to hematology where she underwent a bone marrow biopsy revealing multifocal dense infiltrates of mast cells (≥15 mast cells in aggregates) expressing CD2+ and CD 25+ with 25% showing atypical morphology in bone marrow biopsies. KIT D816V mutation was also positive. The serum tryptase level in this pt was 47.1ug/L. She was then placed on anti-histamines, proton pump inhibitors and steroid therapy. CONCLUSION SM is a clonal disorder of MC that infiltrates one or more organs. It almost always involves the bone marrow. Gastrointestinal (GI) symptoms are present in up to 80% patients. These symptoms are secondary to systemic effects of MC mediators. Incidence of SM in UC has never been established. SM has been shown to mimic Crohn’s disease and is difficult to differentiate based on clinical and endoscopic features. Furthermore, little is known regarding histopathological features of GI involvement in SM. The presence of chronic anemia despite adequate therapy in a clinically/endoscopically inactive UC patient should raise suspicion of other pathologic causes of anemia. Our case highlights the importance of diagnosing the specific cause of anemia in IBD as it may lead to inaccurate clinical judgements of disease flares leading to undue alteration in therapy.

Местные факторы, определяющие ответ на антиангиогенную терапию препаратами первой линии при макулярной неоваскуляризации

Background: the prevalence of macular neovascularization (MNV) is on the rise. However, fundamental data on systemic and local factors determining response to the treatment of MNV have not yet been studied. Aim: to analyze baseline intraocular pressure (IOP) and mean ocular perfusion pressure (mOPP) in patients with MNV in association with the response to antiangiogenic therapy. Patients and Methods: this retrospective cohort study included 84 patients (29 men, 55 women; 92 eyes) with newly diagnosed MNV and signs of disease activity. The age of the patients ranged from 52 to 97 years (mean age 73.4±8.5 years). In 18 (19.5%) patients, MNV was bilateral. IOP and mOPP were measured in all patients with MNV who received fixed-interval intravitreal injections of aflibercept. Treatment results were evaluated clinically and morphometrically by optical coherence tomography. Patients were allocated into five subgroups based on treatment response. A correlation analysis was performed between IOP and mOPP, on the one hand, and treatment outcomes, on the other hand. Results: improvement of MNV activity markers in the setting of treatment manifested as reduction in area and height of subretinal fluid (k=0.9432, p<0.01, and k=0.58959, p<0.001), reduction in height and area of retinal pigment epithelium (RPE) detachment (k=0.82808, p<0.05; k=0.50221, p<0.05) and reduction in sub-RPE fluid (k=0.84515, p<0.05) were strongly directly correlated with baseline IOP. The correlation between IOP and central retinal thickness was negative (k=-0.27266, p<0.05). The biomarker associated with the ideal response was IOP levels of 12.6 mmHg, the balance point, where the sensitivity and specificity of poor response approximately coincided. At this IOP, the sensitivity of poor response was 0.603 and the specificity was 0.737. The IOP was found to be below 12.6 mm Hg in 40% of non-responders and 74% of responders. The 95% confidence interval limits did not overlap, thereby illustrating the reliability of the results (p=0.00784, p<0.01). The range of recommended IOP level for a good treatment response was determined as 11–21 mm Hg. Conclusions: the identification of modifiable risk factors is of paramount importance in the field of practical ophthalmology, as it increases the likelihood of a favorable outcome. Further studies are necessary to investigate the potential for modifying IOP through IOP-lowering therapy prior to intravitreal injection. KEYWORDS: macular neovascularization, antiangiogenic therapy, risk factor, intraocular pressure, mean ocular perfusion pressure. FOR CITATION: Likhvantseva V.G., Kapkova S.G., Tretyak E.B., Rychkova S.I., Gevorkyan A.S., Borisenko T.E. Local factors determining the response to antiangiogenic therapy with first-line drugs in macular neovascularization. Russian Journal of Clinical Ophthalmology. 2024;24(2):69–77 (in Russ.). DOI: 10.32364/2311-7729-2024-24-2-5.

Less, but not gone-gluten-free diet effects on fatigue in celiac disease: a prospective controlled study.

Fatigue is a frequent complaint in patients with celiac disease. A gluten-free diet is the only established treatment for celiac disease, but how this diet influences fatigue is uncertain. We aimed to investigate fatigue prevalence, severity, and associated factors in patients with celiac disease, at diagnosis and at 1 year after commencing a gluten-free diet. 78 patients with serologically and histologically verified celiac disease, 78 age- and sex-matched healthy subjects. Primary endpoints were Fatigue Visual Analog Scale (fVAS), Fatigue Severity Scale (FSS), and inverted Vitality subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36vs). Clinically relevant fatigue was defined as: FSS score ≥ 4, fVAS score ≥ 50 mm, or inverted SF-36vs score ≥ 65. Higher scores represented more fatigue. Fatigue was reduced after a 12-month gluten-free diet. Median scores changed from 3.8 (interquartile range [IQR]: 2.2 to 4.8) to 1.9 (IQR: 1.4 to 3.5) for FSS, from 44.5 (IQR: 18.8 to 66.0) to 15.5 (IQR: 7.8 to 43.3) for fVAS, and from 65 (IQR: 40 to 75) to 35 (IQR: 25 to 55) for inverted SF-36vs (p < 0.001 for all). Fatigue prevalence also declined after treatment. However, scores were significantly higher in patients compared to control subjects. Higher fatigue scores were associated with depression and pain, but not with signs of disease activity or nutritional deficiency. At diagnosis, patients with celiac disease frequently had severe fatigue. Fatigue declined after a gluten-free diet, but it remained higher than that observed in healthy subjects. ClinicalTrials.gov, Identifier NCT01551563.

Trichoscopy of pemphigus vulgaris in remission. A tool for treatment-cessation decision making. Preliminary results

Background: One of the controversies in the treatment of Pemphigus Vulgaris (PV), is the time of treatment cessation. Scalp involvement is often the most stubborn to treatment human area and may reflect disease activity. Trichoscopy (Dermoscopy of hair and scalp) features have not been studied in clinically “healthy-looking” skin of PV patients in full remission. Aims and Objectives:To find out if there are any trichoscopy features in PV patients in clinical and immunologic remission, and accommodate treatment decision. Methods: The age and disease duration of 3 women with PV were correspondingly 62, 63, 55 and 5, 6, 15 years. Treatment at examination was 2,5 mg prednisone(Pr), for the last 22, 5 and 7 months. The 2nd patient was also taking 1 mg/kg/d of Azathioprine. Anti Desmoglein antibodies turned to negative since Oct/2017, Feb/2017, Sept/2015. Contact dermoscopy and hand lens X10 magnifier for clinical evaluation, were used. Results: A red hue background, peripillar scales and tubular casts were observed by trichoscopy in the first 2 patients. Only peripilar scales on a small brown round area were the features in the 3rd patient. Treatment cessation was decided only in this patient, since casts observed in the other two patients, were considered as a consequence of outer root sheath acantholysis and a sign of disease activity. Patients’ follow up justified the aforementioned treatment decisions. Conclusions: Areas of red hue skin background and movable cylindical scales (casts) around hair shafts may be observed, even in the absence of apparent scalp clinical involvement, in PV patients in remission. Since these features may drive physicians to treatment continuation, dermoscopy of the scalp is required in clinically “healthy-looking” PV patients, before a decision of treatment cessation is made. Future studies with greater number of patients, furtherly validated by long term disease course outcome, are needed.

P165 Impact of CFTR modulators on systemic inflammation

Cystic fibrosis is a multiorgan disease characterized by systemic inflammation, with various inflammation markers indicating the level of disease activity. CFTR modulators (CFTRm) have an important impact on the course of disease. Their use in Croatia started in October 2022. Our goal was to see if CFTRm have impact on parameters of systemic inflammation, as a sign of disease activity.

Влияние нутрицевтика на комплексную терапию неоваскулярной возрастной макулярной дегенерации на фоне применения анти-VEGF препарата афлиберцепт

Purpose. Evaluation of efficacy of aflibercept (Eylea®, Bayer, Germany) in combination with nutraceutical Ophtholique® (Sentiss Pharma, India) in treatment of neovascular agerelated macular degeneration (nAMD). Material and methods. 32 patients (32 eyes) with nAMD aged 54 to 75 years, controls – 12 healthy people of same age and gender. Initially, best-corrected visual acuity (BCVA) averaged 0.32±0.05. Clinical and morphological features of nAMD was macular neovascularization (MNV): in 18 patients – type 1; 14 people – type 2. All patients underwent 3 intravitreal injections of aflibercept. Two groups were formed, comparable in terms of BCVA and central retinal thickness (CRT), duration and severity of macular changes, gender, age: the main group (17 patients) – treatment was supplemented with Ophtholique®; comparison group (15 patients) – Ophtholique® was not prescribed. Results. After 1 month after 3 intravitreal injections of aflibercept, all 32 patients had no signs of disease activity. The interval between injections was increased according to the protocol by 2 weeks. After 6 months in the main group, the BCVA increased to 0.61 ± 0.02 due to regression of MNV, a decrease of CRT to control values was noted. In the comparison group, BCVA increased to 0.47 ± 0.03, CRT decreased to control values in 8 out of 15 patients. In 7 patients, BCVA, on the contrary, decreased to 0.30 ± 0.01, while the CRT increased to 421.5 ± 5.2 µm. By 12 months all patients of the main group showed none resumption of MNV activity, complete reattachment of neurosensory retina and pigment epithelium, resorption of intraretinal cystic cavities was noted. In the comparison group MNV activity was noted in 5 eyes with decrease in functional parameters of the retina. Conclusion. Combination of aflibercept in Tread-and-Extend treatment regimen with oral administration of nutraceutical Ophtholique® take it possible to increase efficacy of treatment of nAMD. Keywords: neovascular AMD, anti-VEGF therapy

P581 Early biological therapy within the first 12 months after diagnosis leads to higher clinical, endoscopic, and transmural remission in Crohn’s disease: European multicentre study with a propensity-score matched analysis

Abstract Background Transmural healing (TH) is emerging as a potential treatment target for Crohn′s Disease (CD). While post-hoc analyses of RCTs and observational studies have shown that early introduction of biological therapy leads to higher rates of clinical (CR) and endoscopic remission (ER), no data is available for TH. Our goal was to assess the impact of early biologic introduction (defined as &amp;lt;12 months since diagnosis) in CR, ER, and TH rates. Methods Multicentre retrospective study including 5 European centres. Patients with CD with a baseline (±3 months) either computed tomography enterography (CTE) or magnetic resonance enterography (MRE) with signs of active disease before starting biologics were included. We assessed CR (PRO2&amp;lt;8), ER (SES-CD&amp;lt;3 and no ulcers), and TH (complete normalization of MRE) at 12±3 months following the introduction of biologics. All radiological examinations were read locally after a consensus meeting to list and define clinically relevant lesions and outcomes. Multivariate logistic regression with propensity-score matching also adjusted for previous biologic use was conducted (propensity-score covariates: gender, age at diagnosis, disease location, disease behavior, perianal disease, extra-intestinal manifestations, smoking history, and previous surgery). Results We included 168 patients (51% females), with a median age at diagnosis of 25 years old (IQR 19-34). Median follow-up time after treatment initiation was 73 (IQR 42-98) months and median disease duration was 120 (IQR 76-237) months. Most patients (93%) had ileal involvement (L1 or L3) and an inflammatory phenotype (50%). Overall, 79% were bio naïve and of those 46% were started on early biological treatment. Most patients were started on anti-TNF (89%), 10% on ustekinumab, and 1% on vedolizumab; 58% were on combination therapy (table 1). CR was achieved in 76% (119/157), ER in 52% (64/124), and TH in 32% (30/95). In the multivariate logistic regression model, early initiation of biological treatment was significantly associated with increased probability of achieving CR (OR 4.3, 95%CI 1.6-11.5, p=0.003), ER (OR 2.9, 95%CI 1.2-7.1, p=0.02) and TH (OR 2.7, 95%CI 1.002-7.1, p=0.049). The presence of a stricture in endoscopy was a negative independent factor to predict ER (table 2) and the presence of a stricture and extensive disease in cross-sectional imaging were negative independent factors to predict TH (table 3). Conclusion Introducing biological treatment within the first 12 months after diagnosis was associated with an increased probability of achieving CR, ER, and TH. The presence of a stricture both in endoscopy and in cross-sectional imaging and the radiological extension of the disease may limit the achievement of ER and TH, respectively.

4-Year Multiple Sclerosis Disease Remission After a Single Cycle of Alemtuzumab: a case report

Introduction. Alemtuzumab is a humanized monoclonal antibody against the CD52 antigen. It is a highly efficacious drug for the treatment of relapsing remitting multiple sclerosis (MS). The treatment protocol consists in 2 treatment cycles: 12mg/day i.v. infusions for 5 consecutive days and after one-year 12mg/day infusions for 3 days. To our knowledge, there is a single case series in the literature detailing MS remission after a single cycle of Alemtuzumab. Here, we report a similar experience. Case report. A 48-year-old woman with fluctuating right leg weakness for three years and burning pain in the right foot was diagnosed with MS. She was started on Betaferon©. Her condition progressed and in less than one year, she was switched to glatiramer and after new MS relapses to fingolimod. Disease progressed to Expanded Disability Status Scale (EDSS) of 7.0. She was started on Alemtuzumab (five-day course of 12mg i.v. on 6/2018). A second Alemtuzumab cycle was not given since she failed to follow monitoring guidelines. She had no signs of disease activity after four years. Conclusions. It is possible that MS remission may be achieved with a single cycle of Alemtuzumab.

Clinical Phenotypes of Patients with Neovascular Age-Related Macular Degeneration and Poor Response to Aflibercept Treatment

The purpose: to identify and describe the clinical phenotypes of patients depending on their response to treatment with Aflibercept.Material and methods. The study had a prospective cohort design, including 92 eyes (n = 84) with a newly diagnosed diagnosis of nAMD and signs of disease activity. According to the OCT, the activity and type of macular neovascularization (MNV) were verified. Disease activity was monitored by central retinal thickness (CRT), the presence of subretinal and intraretinal fluid (SRF, IRF), and pigment epithelial detachment (PED). Eyes showing fresh hemorrhage ophthalmoscopically, OCT signs of SRF, IRC or sub-RPE, and dye leakage on the FAG were classified as having active nVMD. Treated with intravitreal injections (IVI) of Aflibercept 40 mg/ml in the “treat and extend” mode. The group with an unsatisfactory response to treatment was divided into 5 subgroups: true non-responders (without changes in activity throughout the course of treatment); partial nonrespondents (minimal regression of SRF and/or IRF) during treatment; dependent on anti-VEGF (complete regression on the background of injections, relapse after 4 weeks (increase in SRF/IRF, sub-RPE fluid, PED size); progression of anatomical changes, with exudation or hemorrhage, despite treatment; decreased response to treatment over time. Studied differences in baseline characteristics between the eyes among respondents and non-respondents and in five subgroups of incomplete respondents.Results. In the OCT characteristic, 45.5 % of eyes with tachyphylaxis showed normal CRT, lack of SRF (90.9 %) and IRF (90.9 %), high prevalence of fibrovascular PED (90.9 %); 90.0 % of the eyes showed type 1 MNV. In the subgroup of non-respondents with anatomical deterioration, type 2 and 3 of MNV were more often present (p = 0.00001) and fibrovascular-hemorrhagic PED was present in every sixth eye. Half (51.2 %) of the VEGF-dependent eyes (p = 0.0139) had the phenotype SRF+ and IRF- (91.3 % vs. 57.9 %, p = 0.0123), dominated by the OCT phenotype: SRF+/IRF-, as well as type 1 and 2 of MNV (91.3 % and 8.7 %, respectively). The eyes are partially non-respondent in 32 % had normal CRT, in 40 % of the eyes SRF+, in 24 % of IRF+, different types of PED, 1 and 3 types of MNV were present.Conclusion. The presented descriptions of clinical phenotypes of eyes with nVMD depending on their response to treatment with Aflibercept may be useful in predicting the response to treatment.

Non-myogenic mesenchymal cells contribute to muscle degeneration in facioscapulohumeral muscular dystrophy patients

Muscle-resident non-myogenic mesenchymal cells play key roles that drive successful tissue regeneration within the skeletal muscle stem cell niche. These cells have recently emerged as remarkable therapeutic targets for neuromuscular disorders, although to date they have been poorly investigated in facioscapulohumeral muscular dystrophy (FSHD). In this study, we characterised the non-myogenic mesenchymal stromal cell population in FSHD patients’ muscles with signs of disease activity, identified by muscle magnetic resonance imaging (MRI), and compared them with those obtained from apparently normal muscles of FSHD patients and from muscles of healthy, age-matched controls. Our results showed that patient-derived cells displayed a distinctive expression pattern of mesenchymal markers, along with an impaired capacity to differentiate towards mature adipocytes in vitro, compared with control cells. We also demonstrated a significant expansion of non-myogenic mesenchymal cells (identified as CD201- or PDGFRA-expressing cells) in FSHD muscles with signs of disease activity, which correlated with the extent of intramuscular fibrosis. In addition, the accumulation of non-myogenic mesenchymal cells was higher in FSHD muscles that deteriorate more rapidly. Our results prompt a direct association between an accumulation, as well as an altered differentiation, of non-myogenic mesenchymal cells with muscle degeneration in FSHD patients. Elucidating the mechanisms and cellular interactions that are altered in the affected muscles of FSHD patients could be instrumental to clarify disease pathogenesis and identifying reliable novel therapeutic targets.

Long-Term Consequences of COVID-19 Lockdown in Neovascular AMD Patients in Spain: Structural and Functional Outcomes after 1 Year of Standard Follow-Up and Treatment.

Consequences of the COVID-19 pandemic on medical care have been extensively analyzed. Specifically, in ophthalmology practice, patients suffering age-related macular degeneration (AMD) represent one of the most affected subgroups. After reporting the acute consequences of treatment suspension in neovascular AMD, we have now evaluated these same 242 patients (270 eyes) to assess if prior functional and anatomical situations can be restored after twelve months of regular follow-up and treatment. We compared data from visits before COVID-19 outbreak and the first visit after lockdown with data obtained in subsequent visits, until one year of follow-up was achieved. For each patient, rate of visual loss per year before COVID-19 pandemic, considered “natural history of treated AMD”, was calculated. This rate of visual loss significantly increased during the lockdown period and now, after twelve months of regular follow-up, is still higher than before COVID outbreak (3.1 vs. 1.6 ETDRS letters/year, p < 0.01). Percentage of OCT images showing active disease is now lower than before the lockdown period (51% vs. 65.3%, p = 0.0017). Although anatomic deterioration, regarding signs of active disease, can be apparently fully restored, our results suggest that functional consequences of temporary anti-VEGF treatment suspension are not entirely reversible after 12 months of treatment, as BCVA remains lower and visual loss rate is still higher than before the COVID-19 pandemic.

ORAL MANIFESTATIONS OF GASTRIC MALT LYMPHOMA: A CASE REPORT

Non-Hodgkin's lymphomas (NHL) are a group of highly diverse malignancies and have a great tendency to affect organs and tissues that normally do not contain lymphoid cells. The objective of the present work is to report the clinical case of patient with NHL from the gastrointestinal tract with oral manifestation. A 40-year-old male sought medical attention due to edema and erythema in the left lower limb that evolved with sudden-onset dyspnea. After an episode of melena, the patient underwent upper digestive endoscopy, which revealed advanced gastric neoplasia and ulceration of the second portion of the duodenum. Histopathologic examination of gastric mucosa showed the presence of gastric lymphoma, MALT type. The patient evolved with multiple tumefactions in the oral cavity, which regressed after cancer chemotherapy. The patient is currently being followed up with no signs of active disease.

Morphological features of the intestinal mucosa in ulcerative colitis in various forms of the disease

Background. Chronic inflammatory bowel disease (CIBD) is one of the most complex nosological groups in gastroenterology, due to the constant increase in their prevalence, shifting the onset to an earlier age, increasing the frequency of severe complicated forms. The most common representative of CIBD is nonspecific ulcerative colitis (UC). At the heart of UC is a diffuse ulcerative-inflammatory lesion of the colon. The leading role in the diagnosis of UC belongs to the comparison of the results of endoscopic and morphological methods of research. The morphological method of colonobiopsy examination in UC is the gold standard of diagnosis and makes it possible to determine the signs of disease activity even in endoscopic remission. In contrast to descriptive histology, pathological anatomy, quantitative morphology complements and clarifies the data of studies conducted by conventional morphological methods from the standpoint of generalized approaches. The purpose of quantitative morphology is the maximum objectification of the study of qualitative and quantitative manifestations of pathological processes, nosological units, their pathogenesis, morphogenesis, as well as the exclusion of measurement errors and, as far as possible, the subjectivity of the researcher. The purpose of the study: to conduct a comparative histological examination of biopsies of the mucous membrane of the colon in patients with UC of different severity of the disease. Materials and methods. Histological examination of intestinal biopsy specimens was performed in 55 patients with ulcerative colitis. Patients were divided according to the severity of the disease. Group I (n=11)— mild form, group II (n=39)— moderate form and group III (n=5)— patients with severe UC. Results. In 63.6% with a mild severity of UC edema was not observed, the condition of the epithelium was unchanged, the architecture is not disturbed. Crypt abscesses were detected in 54.6% of cases, atrophic changes— in 90.9%. Inflammatory infiltrate consisted mainly of neutrophils ((176.0±8.22) per 1 mm2 stroma) and mononuclear cells ((232.4±22.83) per 1 mm2 stroma), which indicates the activation of regenerative functions of the mucous membrane. From morphometric measurements the highest indicator was the height of the crypt epithelium (38.3±1.49) μm. With an moderate degree of UC in 33.3% of cases there was a violation of the integrity of the epithelium, atrophic changes were diagnosed in 23.1% of cases, violations of crypt architecture— in 17.9%, the presence of crypt abscesses— 48.8%, edema— 64.1%. Morphometric measurement of intestinal mucosal biopsies with moderate severity of UC showed the highest crypt depth (452.6±8.12) μm, crypt epithelial height (42.3±0.33) μm and the number of goblet cells (26.6±1.43). The height of the crypt epithelium was positively correlated with the number of goblet cells (r=0.30; p &lt;0.05). Erosions, general epithelial disorders, crypt abscesses, and atrophic changes were observed in the majority of patients with severe UC in 40%. In severe UC, the smallest crypt depth (426.1±22.37) μm, crypt epithelial height (36.0±2.57)μm, the number of goblet cells (10.5±1.04) and the largest epithelial thickness were observed (51.5±2.81) μm. Conclusions. The presence of crypt abscesses was mainly observed in the group of mild and moderate forms of the disease. Mucosal edema was more common in the group with moderate severity disease. Increased numbers of eosinophils and neutrophils were observed in the group with severety disease.

A Prospective Cross-Sectional Study on the Comparison of Ultrasound Assessment vs. Palpation in Chronic Lymphocytic Leukemia Patients in the Era of Targeted Therapy.

Background. In IWCLL guidelines, progressive splenomegaly and lymphadenopathy are signs of active disease. In this study, we have tested the hypotheses if US could be a reliable tool for both superficial lymphnodes (SupLNs) and splenic assessment in chronic lymphocytic leukemia (CLL) patients. Methods. We enrolled N = 75 patients. SupLN and the spleen were assessed by two independent physicians (M1 and M2) by palpation and by a third physician (M3) with ultrasound sonography (US) using two different sonographers (US1 and US2). The results of M1 vs. M2 assessment, US1 vs. US2, palpation vs. US were compared. The echostructure of N = 1037 SupLN and of the spleen was also investigated. Results. The dimensions of SupLNs assessed by MD1 vs. MD2 were statistically discordant. Splenic size was concordant. There was concordance between US1 and US2 SupLN and splenic assessment. US found a higher number of pathological SupLN (Cohen’s Kappa < 0.1) than palpation, which misses remarkable-sized SupLNs. LN echostructure and splenic involvement patterns were described. Conclusions. US is a reliable, radiation-free tool useful in clinical practice to assess SupLN and splenic involvement in CLL.

Intensive regimens of chemotherapy with hematopoetic stem cell rescue in paediatric patients with high-risk malignant tumors

Background. One of the possible options to intensify therapy in patients with high-risk malignant tumors is high-dose chemotherapy (HDCT) with autologous hematopoetic stem cell rescue. However, this method has a high risk of acute and delayed toxicity, and, sometimes doesn’t meet the expected effectiveness. This confirms the necessity of more considerate approach for choosing the category of patients for this therapeutic option with the determination of the most significant factors on the part of the patient and the type of malignant tumor.Objective. Analysis of the results of HDCT with autologous hematopoetic stem cell transplantation (HSCT) in children with high-risk solid malignancies, conducted in the Department of pediatric oncohematology and BMT of the Federal State Budgetary Institution “V.A. Almazov National Medical Research Center”.Design and methods. We perform a retrospective analysis of 55 cycles of HDCT with autologous hematopoetic stem cell rescue provided from 2017 to 2020 in 39 patients with high-risk malignant tumors. The toxicity and efficacy of the method were assessed taking into account the frequency of infectious complications, early post-transplant mortality, event-free (EFS) and overall survival (OS).Results. The predominant category of patients were children with CNS tumors (61.5 %). Mean age of the patients was 2 years 9 months. At the time of HDCT 35.9% of patients were in complete remission (CR), 64.1 % had signs of active disease (AD). In 59% of patients, one course of HDCT was performed, in 41 % — tandem transplantation was performed according to the recommendations of the protocol for the treatment of the disease. The most common conditioning regimen was carboplatin + etoposide (27.3 %). The predominant source of hematopoietic stem cells were peripheral stem cells (87.3 %). The frequency of infectious complications in the post-transplant period was 100 %, neutropenic enterocolitis (61.8 %) and febrile neutropenia (34.5 %) were predominant. A high frequency of reactivation of CMV infection (25.4 %) was noted, meanwhile CMV disease occurred in 35.7 % of cases. The most important prognostic factor was the disease status at the time of HDCT. 2-year OS incidence of 85.7 % vs 65.3% and EFS 85.7 % vs 39 % in patients with CR and AD respectively. After completing the course of HDCT with autologous HSCT 94.8 % of patients continued anticancer therapy.Conclusion. HDCT with autologous HSCT demonstrates a satisfactory toxicity profile and can improve OS and EFS in children with high-risk malignant tumors. A reliable prognostic factor that determines the effectiveness of the method is the disease status at the time of HDCT.

Immunological changes following electroconvulsive therapy in multiple sclerosis

IntroductionElectroconvulsive therapy (ECT) is a well-established treatment option in case of treatment-resistant depression (TRD). Only a few cases of ECT in depressed patients with multiple sclerosis (MS) were reported so far suggesting efficacy for the treatment of severe depression in MS, while data on possible neurological deterioration remained unclear. MethodsIn this case study we report on a case of a middle-aged man with MS. He was on dimethyl fumarate for relapse prevention since 2019 and without signs of active disease in a recent cerebral MRI. He suffered from treatment-resistant severe bipolar depression and thus received a total of 14 ECT sessions. We changed from right-unilateral to bilateral stimulation technique after the 7th session. We rated depression severity and measured biomarkers of neurodegeneration and inflammation before and after the ECT series to determine the impact of ECT on tolerance, response and neurobiology. ResultsThe ECT series was tolerated well without neurological deterioration and any new neurological symptoms. The seizure quality was sufficient on average. We saw partial response corresponding to an improvement of about 35% in BDI-II and MADRS. The concentration of inflammation and neurodegeneration biomarkers was low both pre-treatment and post-treatment with increases from pre- to post ECT mainly in the CCL-2 pathway. ConclusionIn our patient with TRD and MS ECT was safe and feasible. We did not see any neurobiological signs of disease activation of MS or neurodegeneration during the course of ECT, which may even be beneficial as it led to increase in the neuroprotective CCL-2 pathway in the presented patient.