Start Of Therapy Research Articles

Recurrent Betaherpetic Keratitis. Therapy Stages and Monitoring Methods of the Disease Dynamics

Purpose: to propose a step­by­step treatment regimen for betaherpetic keratitis with a method for monitoring the dynamics of the disease.Patients and methods. The study group included 40 patients (40 eyes). Each patient had a history of diagnosed unilateral recurrent acute or subacute keratitis, the etiology of the betaherpetic process was confirmed by laboratory diagnostic methods, confocal microscopy, based on the detection of specific “owl eye” cells. All subjects had previously received specific therapy with acyclovir. All patients underwent an ophthalmological examination, and then a two­stage treatment regimen for keratitis was proposed. The main way to assess the dynamics of the disease, the presence of viral load and the need to intensify antiviral therapy was confocal microscopy data. The condition was assessed 1, 3, 6 and 12 months after the start of therapy. Results. As a result of the observation of a group of patients of 40 people, after 12 months, 33 patients achieved stable remission, 4 patients developed neurotrophic keratitis, and 3 patients had a relapse of betaherpetic keratitis. Recurrence of keratitis in 3 patients was detected within 2 to 4 months from the start of observation. Neurotrophic keratitis developed in 4 patients within 3 to 6 months from the start of observation.Conclusion. 1) The method of in vivo confocal microscopy can be used to monitor the dynamics of betaherpetic keratitis, based on the state of specific cells. 2) Therapy of betaherpetic keratitis requires the use of specific antiviral drugs with mandatory repeated preventive courses. 3) A history of herpesvirus infection requires assessment of the development of neurotrophic keratitis.

COMBAT-MS: A Population-Based Observational Cohort Study Addressing the Benefit-Risk Balance of Multiple Sclerosis Therapies Compared with Rituximab.

To assess comparative effectiveness, safety, and tolerability of off-label rituximab, compared with frequently used therapies approved for multiple sclerosis (MS). A Swedish cohort study of persons with relapsing-remitting MS, age 18 to 75 years at inclusion and with a first therapy start or a first therapy switch between 2011 and 2018. Low-dose rituximab was compared with MS-approved therapies. Primary outcomes were proportions with 12 months confirmed disability worsening and change in MS Impact Scale-29 (MSIS-29) scores, respectively. Secondary endpoints included relapses, therapy discontinuation, and serious adverse events. Analyses used an intention-to-treat approach and were adjusted for demographics, MS features, and health characteristics. We included 2,449 participants as first therapy start and 2,463 as first therapy switch. Proportions with disability worsening at 3 years were 9.1% for rituximab as first therapy and 5.1% after therapy switch, with no differences to MS-approved comparators. Worsening on rituximab was mostly independent of relapses. MSIS-29 with rituximab at 3 years improved by 1.3/8.4 points (physical/psychological) for first disease-modifying therapy (DMT) and 0.4/3.6 for DMT switch, and was mostly similar across therapies. Rituximab had lower relapse rates and higher therapy persistence in both groups. The rate of hospital-treated infections was higher with rituximab after a therapy switch, but not as a first therapy. This population-based real-world cohort study found low rates of disability progression, mostly independent of relapses, and without significant differences between rituximab and MS-approved comparators. Rituximab led to lower rates of inflammatory activity and higher treatment persistence, but was associated with an increased rate of serious infections. ANN NEUROL 2024.

Антиоксидантная терапия в коррекции ДНК-фрагментации сперматозоидов.

Introduction. The progressive deterioration of reproductive function, observed throughout the world in recent decades, is an extremely alarming trend, while the incidence of male infertility is increasing. The universal pathogenetic mechanism of spermatogenesis disorders, which underlies almost all forms of male infertility, is oxidative stress of sperm. It has various manifestations, the essence of which, as a rule, boils down to the formation of mitochondrial dysfunction and fragmentation of sperm DNA. It has been found that consuming antioxidants and microelements helps increase the chances of conception for subfertile couples, and also reduces the risk of reproductive losses. Of greatest and justifiable interest are medicinal complexes designed to reduce the level of oxidative stress and sperm DNA fragmentation. The purpose of the study was to evaluate the effect of antioxidant therapy on the degree of sperm DNA fragmentation in men suffering from infertility. Materials and methods. The study involved 42 men aged 25 to 37 years with an established diagnosis of male infertility who were treated at the Center for Family Health and Reproduction. The patients were divided into 2 groups, comparable according to the main criteria assessed. Patients in the control group (12 people, 29%) received standard antioxidant therapy. Patients of the main group (30 people, 71%) received the BESTFertil-DHA® complex. The course of treatment for patients in both groups was 3 months. Control examinations were carried out at 1.5 and 3 months from the start of therapy. Spermogram data and assessment of the degree of DNA fragmentation in sperm using the SCD (Sperm chromatin dispersion test) method were used as the main criterion for assessing the effectiveness of therapy. Results. After three months of taking BESTFertil-DHA®, in 16 patients (53%), the degree of sperm DNA fragmentation decreased to less than 15%. Against this background, 5 couples became pregnant naturally, and 4 couples became pregnant as a result of the in vitro fertilization procedure. The average level of sperm DNA fragmentation was less than 13% (p < 0.05). A decrease in the level of DNA fragmentation was noted in 53% of patients after 1.5 months of taking BESTFertil-DHA®, which is especially important when preparing patients for assisted reproductive technology programs. In patients taking BESTFertil-DHA®, the total progressive motility of spermatozoa «A+B» increased by 28%, and the concentration of spermatozoa in 1 ml of ejaculate – by 61%. In the control group, the degree of sperm DNA fragmentation did not undergo statistically significant changes during treatment. Conclusion. BESTFertil-DHA® statistically significantly helps to reduce the degree of DNA fragmentation in sperm, increase the number of actively motile forms of sperm and reduce the degree of teratozoospermia.

Survival and its relationship with the type of peritoneal solute transfer rate, in patients with chronic kidney disease incident on peritoneal dialysis therapy in RTS Colombia between the years 2007–2017

IntroductionIn some studies, the peritoneal solute transfer rate (PSTR) through the peritoneal membrane has been related to an increased risk of mortality. It has been observed in the literature that those patients with rapid diffusion of solutes through the peritoneal membrane (high/fast transfer) and probably those with high average transfer characterized by the Peritoneal Equilibrium Test (PET) are associated with higher mortality compared to those patients who have a slow transfer rate. However, some authors have not documented this fact. In the present study, we want to evaluate the (etiological) relationship between the characteristics of peritoneal membrane transfer and mortality and survival of the technique in an incident population on peritoneal dialysis in RTS Colombia during the years 2007–2017 using a competing risk model. Materials and methodsA retrospective cohort study was carried out at RTS Colombia in the period between 2007 and 2017. In total, there were 8170 incident patients older than 18 years, who had a Peritoneal Equilibration Test (PET) between 28 and 180 days from the start of therapy. Demographic, clinical, and laboratory variables were evaluated. The (etiological) relationship between the type of peritoneal solute transfer rate at the start of therapy and overall mortality and technique survival were analyzed using a competing risk model (cause-specific proportional hazard model described by Royston-Lambert). ResultsPatients were classified into four categories based on the PET result: Slow/Low transfer (16.0%), low average (35.4%), high average (32.9%), and High/Fast transfer (15.7%). During follow-up, with a median of 730 days, 3025 (37.02%) patients died, 1079 (13.2%) were transferred to hemodialysis and 661 (8.1%) were transplanted. In the analysis of competing risks, adjusted for age, sex, presence of DM, HTA, body mass index, residual function, albumin, hemoglobin, phosphorus, and modality of PD at the start of therapy, we found cause-specific HR (HRce) for high/fast transfer was 1.13 (95% CI 0.98–1.30) p = 0.078, high average 1.08 (95% CI 0.96–1.22) p = 0.195, low average 1.09 (95% CI 0.96–1.22) p = 0.156 compared to the low/slow transfer rate. For technique survival, cause-specific HR for high/rapid transfer of 1.22 (95% CI 0.98–1.52) p = 0.66, high average HR was 1.10 (95% CI 0.91–1.33) p = 0.296, low average HR of 1.03 (95% CI 0.85–1.24) p = 0.733 compared with the low/slow transfer rate, adjusted for age, sex, DM, HTA, BMI, residual renal function, albumin, phosphorus, hemoglobin, and PD modality at start of therapy. Non-significant differences. ConclusionsWhen evaluating the etiological relationship between the type of peritoneal solute transfer rate and overall mortality and survival of the technique using a competing risk model, we found no etiological relationship between the characteristics of peritoneal membrane transfer according to the classification given by Twardowski assessed at the start of peritoneal dialysis therapy and overall mortality or technique survival in adjusted models. The analysis will then be made from the prognostic model with the purpose of predicting the risk of mortality and survival of the technique using the risk subdistribution model (Fine & Gray).

Impact of the COVID-19 Pandemic on Thyroid Cancer Surgery.

The COVID-19 pandemic caused major disruptions to healthcare services in 2020, delaying cancer diagnosis and treatment. While early-stage thyroid cancer often progresses slowly, it is crucial to determine whether treatment delays associated with the pandemic have impacted the clinical presentation and management of advanced-stage thyroid cancer. The purpose of our study was to determine the impact of the early COVID-19 pandemic on thyroid cancer presentation and treatment times. Utilizing the National Cancer Database, chi-squared tests and regression analyses were performed to compare patient demographic and clinical characteristics over time for 56,011 patients diagnosed with primary thyroid cancer who were treated at the Commission on Cancer-accredited sites in 2019 and 2020. We found that thyroid cancer diagnoses decreased between 2019 and 2020, with the biggest drop among patients with cT1 disease relative to other T stages. We also found that patients diagnosed with thyroid cancer in 2020 had similar treatment times to patients diagnosed in 2019, as measured by both the time between diagnosis and start of treatment and the time between surgery and start of radioactive iodine therapy. Overall, our study suggests that resources during the pandemic were allocated to patients with advanced thyroid disease, despite a decrease in diagnoses.

Retrospective study on pomalidomide-PACE as a salvage regimen in aggressive relapsed and refractory multiple myeloma.

Despite major advances in treatment options for multiple myeloma (MM), patients refractory to the main drug classes and those with aggressive, especially extramedullary disease, still face a dismal outcome. For these patients, effective therapeutic options are urgently warranted. In this retrospective study, we report on the safety and efficacy of the intensive combination regimen of pomalidomide plus cisplatin, doxorubicin, cyclophosphamide, and etoposide (Pom-PACE) in patients with relapsed refractory MM (RRMM) or plasma cell leukemia (PCL). A study population of 20 consecutive patients treated with Pom-PACE at two academic centers was included for analysis. All patients had to have a confirmed relapse according to International Myeloma Working Group criteria and adequate organ function prior to the start of therapy. Data were collected by reviewing medical charts. Exploratory analyses were performed with regard to efficacy and safety. Patients were heavily pretreated with a median number of four prior therapies (range: 1-10). All patients were exposed to immunomodulators, proteasome inhibitors, and alkylating agents, 80% were double-class refractory, 40% were triple-class refractory. Extramedullary MM or PCL were present in 15 patients (75%). Overall response rate (ORR) was 68%, with 31% achieving at least a very good partial response. Responses were achieved rapidly with an ORR of 64% after one cycle. Median progression-free survival was 8.9 months (0.92-not reached [NR]) and median overall survival was 11.8 months (3-40.6). Pom-PACE was associated with significant toxicity. All evaluable patients experienced Grade 4 hematological toxicity. However, no treatment related mortality was observed. Pomalidomide-PACE was able to induce rapid responses in heavily pretreated, aggressive RRMM with a manageable toxicity profile and therefore offers an effective salvage regimen and a potential bridging strategy to further treatment options such as chimeric antigen receptor T-cell therapy.

Hematological Predictors of Antipsychotic-induced Metabolic Syndrome in a Female Patient with Schizophrenia: Case Report

Schizophrenia is a chronic mental disorder. It is treated with antipsychotics, which have a high risk of adverse reactions. One of these adverse reactions is metabolic syndrome, which increases the risk of cardiovascular diseases and the mortality rate of patients with schizophrenia. Various studies have shown an association between hematological parameters and metabolic syndrome. In this regard, the use of hematological predictors as a diagnostic tool can help identify risks and timely correct antipsychotic therapy for preventing metabolic syndrome. One of the most promising predictors are hematological inflammation coefficients obtained on the basis of a clinical blood test. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and the index of systemic immune inflammation (SII), are inexpensive, easy-to-detect markers of systemic inflammation. This case report of a 48-year-old female patient with paranoid schizophrenia, hematological inflammation coefficients were increased during antipsychotic therapy compared to the baseline. At the start of clozapine therapy, the highest levels of systemic inflammatory markers were recorded, after which the patient developed metabolic syndrome. In this case, stopping clozapine therapy when the level of hematological inflammatory coefficients increases would prevent the development of metabolic syndrome in the patient. Markers of systemic inflammation can help doctors diagnose metabolic syndrome early. This may reduce rates of cardiovascular disease and type 2 diabetes and thus reduce mortality in patients with schizophrenia. This case report demonstrates that wider implementation of hematological predictors of metabolic syndrome into real clinical practice could help significantly improve the safety of antipsychotic therapy.

CO139 Comparative Effectiveness of Rapid Vs. Non-Rapid Start of Anti-Retroviral Therapy in Patients With Human Immunodeficiency Virus Infection on Clinical Outcomes: A Systematic Literature Review and Meta-Analysis

CO139 Comparative Effectiveness of Rapid Vs. Non-Rapid Start of Anti-Retroviral Therapy in Patients With Human Immunodeficiency Virus Infection on Clinical Outcomes: A Systematic Literature Review and Meta-Analysis

A case of congenital malformation of the brain in a newborn on the background of hereditary metabolic disorders

A clinical observation of congenital malformation of the brain in a newborn child is presented. Diagnosis and comprehensive treatment of newborns with such pathology is extremely difficult due to the variety of causes that cause irreversible structural defects of brain tissue in violation of its normal pre- or postnatal development. The uniqueness of this case is the postnatal detection of multiple malformations in a newborn child against the background of a complex clarification of the nature of hereditary metabolic disorders. Unfortunately, in this clinical case, the relatively early diagnosis of peroxisomal pathology did not allow a complete clinical diagnosis to be made quickly and specific therapy to be given to the child, which made the prognosis of the disease more difficult. Only a further in-depth examination (consultations of a geneticist, neurologists, MRI of the brain, medical and genetic research) allowed us to clarify the nature of the pathology. Delayed clarification and confirmation of the cause of encephalomyelopathy (peroxisomal disease) is associated with the material and technical capabilities of children's hospitals, although this did not affect the timing of the start and volume of complex symptomatic therapy for the child.

Course of Uveitis in Patients with Ankylosing Spondylitis during the Interleukin17 Inhibitors Therapy.

Biological disease-modifying antirheumatic drugs (bDMARDs) can have different effects on various clinical manifestations of ankylosing spondylitis (AS). Data on the effects of interleukin 17 inhibitors (IL17-i) on uveitis in AS continue to accumulate. Objective: to evaluate the effect of IL17-i therapy on the course of uveitis in AS. The study involved 73 patients with AS (New York criteria, 1984), who received IL17-i (57-secukinumab (SEC), 22-netakimab (NTK)) for at least 1 year. The average age of patients at the time of inclusion in the study was 41.93 ± 8.95 years, the average duration of AS was 10.75 ± 6.22 years. There were 40 men (56.7%) and 33 women (43.3%) among the patients. HLA-B27 was detected in 62/73 (85%), coxitis in 58 (79%), enthesitis in 63 (86.3%), peripheral arthritis in 57 (78%), psoriasis in 7 (9.5%), and inflammatory bowel disease (IBD) in 3 (4.1%) patients; in 6 (8.2%) patients, the disease started before the age of 16; 19 (26%) patients had at least one episode of uveitis during the course of the disease. The rates of uveitis was estimated by comparing the number of incidences per 100 patient-years before the start of bDMARDs therapy and during IL17-i using. The incidence rate of uveitis before the start of bDMARDs therapy for all patients was 8.3 per 100 pt-years (95% CI 0.065-0.107), during IL17-i therapy- 9.2 per 100 pt-years (95% CI 0.06-0.15), p = 0.72. The incidence rate of uveitis among patients who used SEC was 10.1 per 100 pt-years (95% CI 0.079-0.13) before the start of bDMARDs therapy and 9.4 per 100 pt-years (95% CI 0.05-0.15), p = 0.74 during SEC therapy. The incidence rate of uveitis among patients who used NTK was 4.8 per 100 pt-years (95% CI 0.028-0.08) before the start of bDMARDs therapy and 7.1 per 100 pt-years (95% CI 0.019-022), p= 0.3 during the NTK therapy. For patients with a history of uveitis, the incidence rate of uveitis was 22.5 per 100 pt-years (95% CI 0.18-0.28) before the start of therapy with bDMARDs and 29.1 per 100 pt-years (95% CI 0.18-0.43), p = 0.29 during IL17-i therapy. Occurrences of uveitis were observed in 4 of 57 patients (7%) during SEC therapy and in 1 of 25 (4%) patients during the NTK therapy. One case of new-onset uveitis was recorded during the using of SEC. There were no significant differences in the incidence rates of uveitis during IL17-i therapy compared with non-biological therapy. IL17-i therapy have not demonstrated a significant effect on the course of uveitis in AS in the study group.

Clinical study (phase II) of the efficacy and safety of Longidase (suppositories) in patients with adhesions due to pelvic inflammatory disease: A blinded, placebo-controlled, randomized study

Background. Pelvic inflammatory disease (PID) is a significant gynecological problem. The main treatment strategy involves antibacterial drugs to eliminate the infection in combination with anti-inflammatory, infusion, transfusion, anticoagulant, and desensitization therapy. Chronic inflammatory processes can induce changes in the immune system, thus reducing the effectiveness of treatment, causing adhesions, obstruction of the fallopian tubes, and infertility. It emphasizes the importance of developing new PID treatment methods, including using agents with immunomodulatory, antioxidant, and enzymatic activity that can increase the body's overall resistance to infections. Aim. To evaluate the effectiveness of Longidase® in treating pelvic adhesions to improve the outcomes in chronic PID. Materials and methods. The study included 50 women of reproductive age with established chronic PID and adhesions aged 18 to 42 years with a mean age of 29.4±5.8 years. The subjects were randomly assigned to two groups comparable in their main prognostic features. Patients of the main group (30 people) received treatment with Longidase® 3000 IU 1 suppository rectally once every 3 days, 10 doses, then 1 suppository once every 5 days, 5 doses (the total course is 15 doses of Longidase suppositories 3000 IU). Patients in the control group (20 people) received placebo. The treatment course was 55 days. The patients were followed up for up to 140 days from the start of therapy. Results. The results show no significant changes and the negative effect of the treatment on the blood chemistry parameters in both groups. In 35% of patients in the main group, the level of peptide-bound oxyproline did not change; 46% responded to therapy with its increase and 11% with a decrease, which indicates the activation of the decomposition of collagen proteins and a decrease in their synthesis. Analysis of individual levels of circulating immune complexes (CIC) before and after treatment showed a significant decrease in CIC in the main group (Longidase) vs. control group (36.1±1.4 and 30.8±0.8, respectively), which indicates a decrease in the severity of the inflammation. The pain relief, more pronounced during treatment in the main group than in the control group (30% vs. 15%), is probably due to the resolution of the chronic inflammation and correlates with changes in CIC. The onset of pregnancy in 10 (33.3%) patients in the main group indicates the effectiveness of bovhyaluronidase azoximer (Longidase®) as an anti-inflammatory and anti-fibrotic agent. Conclusion. The study showed the possibility of using Longidase 3000 IU suppositories in the complex therapy of patients with pelvic adhesions due to chronic PID

Adjuvant PD-1 blockade with camrelizumab in high-risk locoregionally advanced nasopharyngeal carcinoma (DIPPER): A multicenter, open-label, phase 3, randomized controlled trial.

LBA6000 Background: Patients with high-risk locoregionally advanced nasopharyngeal carcinoma (NPC) often experience disease relapse even after receiving standard-of-care treatment, e.g. induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). The benefit of PD-1 inhibitor as adjuvant treatment following IC+CCRT in locoregionally advanced NPC remains unclear. Methods: Patients with high-risk locoregionally advanced NPC (T4N1M0 or T1-4N2-3M0) who have received gemcitabine and cisplatin (GP) IC and CCRT were recruited at 11 centers in China. They were randomly assigned (1:1) within 2 weeks after the last radiation dose to receive intravenous camrelizumab (200 mg once every 3 weeks for 12 cycles; Camrelizumab Arm) or observation (Standard-therapy Arm). The primary endpoint was event-free survival (EFS). It is estimated that approximately 442 patients would provide 80% power to detect a hazard ratio (HR) of 0.52 with a log-rank test at a two-sided α level of 0.05. Quality of life (QoL) was assessed by EORTC-C30. Results: A total of 450 patients were randomly assigned to the Camrelizumab Arm (n=226) and the Standard-therapy Arm (n=224). After a median follow-up of 37 months (corresponding to 41 months when calculated from the start of standard therapy), the estimated 3-year EFS was 86.9% in the Camrelizumab Arm and 77.4% in the Standard-therapy Arm (intention-to-treat population; HR 0.61, 95% CI 0.38–0.96; P = 0.03). The incidence of grade 3-4 adverse events (AEs) was 11.2% in the Camrelizumab Arm and 3.2% in the Standard-therapy Arm, including grade 3-4 immune-related AEs in 8 (3.9%) patients in the Camrelizumab Arm. Reactive capillary endothelial proliferation was the most common adverse event related to camrelizumab (RECP, 87.8%, 4 (1.8%) patients had grade 3 RECP). Treatment-related deaths occurred in 1 (<1%) patients in the Camrelizumab group (subarachnoid hemorrhage) and 1 (<1%) patients in the Standard-therapy group (nasopharyngeal necrosis). During treatment, there was no clinically meaningful deterioration of health-related quality of life associated with the use of adjuvant camrelizumab. Conclusions: Adjuvant PD-1 blockade with camrelizumab significantly improved EFS in high-risk locoregionally advanced NPC, with mild toxicity and comparable quality of life. Clinical trial information: NCT03427827 . [Table: see text]

Primary outcome analysis of the ORCHESTRA trial: A randomized phase III trial of additional tumor debulking to first-line palliative systemic therapy for patients with multiorgan metastatic colorectal cancer.

LBA3502 Background: The phase-3, investigator-initiated, ORCHESTRA trial (NCT01792934) was conducted to prospectively evaluate overall survival (OS) benefit from tumor debulking in addition to standard palliative systemic therapy in patients with multiorgan metastatic colorectal cancer (mCRC). Local therapy of metastases is increasingly discussed as part of the treatment plan for patients with multiorgan mCRC in analogy to selected patients with oligometastatic disease for whom this is standard of care. Treatment decisions are made on a daily base in multidisciplinary teams (MDT) worldwide, but evidence of superiority for additional local therapy over systemic therapy alone based on a head-to-head comparison is lacking. Methods: Between May 2013 and May 2023, 454 patients were enrolled in 28 hospitals. Patients with multiorgan mCRC as described in Table, were eligible if at least 80% tumor debulking was deemed feasible by resection, radiotherapy and/or thermal ablative therapy at the start of first-line palliative systemic therapy according to the MDT. Upon clinical benefit after 3 or 4 cycles of respectively capecitabine or 5-fluorouracil/leucovorin and oxaliplatin ± bevacizumab, 382 patients were randomized 1:1 to continuation with systemic therapy alone in the standard arm or to tumor debulking followed by restart of the systemic therapy in the experimental arm. The primary endpoint was OS, from the date of inclusion to the date of death. Secondary endpoints included progression free survival (PFS) and treatment related adverse events. OS and PFS were analyzed by means of multivariable Cox proportional hazards regression analysis where the variables used in the randomization process were included as covariates. Results: 382 patients were randomized to either receive standard palliative systemic therapy in the standard arm (N=192) or to receive additional tumor debulking to palliative systemic therapy in the experimental arm (N=190). Baseline characteristics of patients were in standard arm versus (vs) experimental arm: median age 64 vs 64 years, male 69% vs 67%, >2 organs involved 38% vs 40%, baseline LDH >250 U/L 17% vs 16%, baseline CEA >200 ng/ml 5% vs 8%. At data cut-off on April 4th, 2024, a total of 153 OS events were observed in the standard arm and 155 OS events in the experimental arm. Median follow up was 32.3 months. Median OS in the standard arm was 27.5 months versus 30.0 months in the experimental arm (adjusted HR 0.88 [95% CI 0.70-1.10] p=0.225). Median PFS in the standard arm was 10.4 months versus 10.5 months in the experimental arm (adjusted HR 0.83 [95% CI 0.67-1.02], p=0.076). Details on local treatment modalities being applied, including rate of successful radical debulking and related adverse events, will be presented at the meeting. Conclusions: Additional tumor debulking to standard first-line palliative systemic therapy failed to improve overall survival for patients with multiorgan metastatic colorectal cancer. The increasing use of local therapies for patients with mCRC needs further consideration. Clinical trial information: NCT01792934 . [Table: see text]

Imaging in malignant germ cell tumors involving the hypothalamo-neurohypophyseal axis: the evaluation of the posterior pituitary bright spot is essential

PurposeMalignant intracranial germ cell tumors (GCTs) are rare diseases in Western countries. They arise in midline structures and diagnosis is often delayed. We evaluated imaging characteristics and early tumor signs of suprasellar and bifocal GCT on MRI.MethodsPatients with the diagnosis of a germinoma or non-germinomatous GCT (NGGCT) who received non-contrast sagittal T1WI on MRI pre-therapy were included. Loss of the posterior pituitary bright spot (PPBS), the expansion and size of the tumor, and the expansion and infiltration of surrounding structures were evaluated. Group comparison for histologies and localizations was performed.ResultsA total of 102 GCT patients (median age at diagnosis 12.3 years, range 4.4–33.8; 57 males; 67 in suprasellar localization) were enrolled in the study. In the suprasellar cohort, NGGCTs (n = 20) were noticeably larger than germinomas (n = 47; p < .001). Each tumor showed involvement of the posterior lobe or pituitary stalk. A PPBS loss (total n = 98) was observed for each localization and entity in more than 90% and was related to diabetes insipidus. Osseous infiltration was observed exclusively in suprasellar GCT (significantly more frequent in NGGCT; p = .004). Time between the first MRI and therapy start was significantly longer in the suprasellar cohort (p = .005), with an even greater delay in germinoma compared to NGGCT (p = .002). The longest interval to treatment had circumscribed suprasellar germinomas (median 312 days).ConclusionA loss of the PPBS is a hint of tumor origin revealing small tumors in the neurohypophysis. Using this sign in children with diabetes insipidus avoids a delay in diagnosis.

Chronic adenoiditis and its effect on the reactivity of the bronchopulmonary system, the possibility of non-drug correction

Introduction. In pediatric otorhinolaryngological practice, chronic adenoiditis is one of the most common diseases and causes the search for additional and effective methods of treatment.Aim. To evaluate the clinical effectiveness of the use of aqueous solutions treated with low-frequency ultrasound with high specific energy and monochromatic light radiation in the complex therapy of chronic adenoiditis in children.Materials and methods. The number of participants in the study was 104 patients aged 4 to 15 years with a verified diagnosis of chronic adenoiditis and were divided into 3 groups depending on the treatment. A comparative analysis of the results obtained was carried out before the start of therapy (day 0) and on the 7th day after the treatment. The state of the nasopharynx was assessed using a flexible nasopharyngoscope, as well as the structure of the middle ear and auditory tube during acoustic impedancemetry.Results. The use of a course of treatment of low-frequency ultrasonic cavitation in combination with photochromotherapy made it possible to relieve the signs of chronic adenoiditis in 62% of cases (p &lt; 0.001), reduce the number of patients with grade III adenoid hypertrophy by 54% (p = 0.035), and reduce by 2 times (p = 0.05) number of relapses of chronic adenoiditis. In the group of children using low-frequency ultrasonic cavitation, the positive effect of treatment was 3.3 times [CI 0.75; 14.6] higher compared to the control group, and in combination with photochromotherapy it was 3.6 times [CI 0.85; 15.5]. The absence of adenotomy was assessed as a positive effect.Conclusion. The data obtained showed that the inclusion of non-drug methods of physical influence (low-frequency ultrasonic cavitation both in monotherapy and in combination with photochromotherapy) in complex treatment can reduce the number of surgical interventions on the organs of the lymphopharyngeal ring – the pharyngeal tonsil.

Characteristics of Immunological Non-Responders in People Living with HIV at Abepura Hospital Papua

Infection of Human Immunodeficiency Virus (HIV) lowers the body's immune system, especially CD4+ cells, making it more susceptible to opportunistic infections. Approximately 10-40% of People Living with HIV/AIDS (PLHIV) fail to achieve normal levels of CD4+ T cells despite continued virological suppression, a condition called Immunological Non-Responders (INR). Previous studies have shown that INR is considered a predictor of disease progression in people with HIV receiving antiretroviral (ARV)s through various mechanisms of suppression of the immune system that increases morbidity and mortality. Papua is an HIV epidemic area with a prevalence of 2.3%. This research is a cohort study conducted at Abepura Hospital from June 2019 to February 2023, which aims to identify the factors that influence the occurrence of INR in PLHIV receiving ARV therapy. There were 123 research subjects consisting of 55 people (44.7%) in the INR group and 68 people (55.3%) in the non-INR group. The results showed that the incidence of INR was higher in males than females (p=0.019), INR was significantly associated with increasing age (p=0.013), and CD4 count was low at the start of ARVs (p=0.002). There was a significant difference in CD4 counts between INR and non-INR (p&lt;0.001). Oral candidiasis as a common opportunistic infection is more common in people with INR than in non-INR. (p=0.037). This study suggested that it is necessary to carry out a CD4 examination at the start of therapy and monitoring every 6 months to detect possible INR to prevent an increased risk of AIDS and non-AIDS, which increases mortality.

Direct comparative study of anti-IgE and anti-IL4Rα therapy effectiveness in patients with severe allergic and mixed bronchial asthma

Introduction. There is insufficiency of direct comparative studies of genetically engineered biological drugs (GEBD) for severe bronchial asthma (SA) treatment in scientific databases.Aim. To compare omalizumab and dupilumab effectiveness in patients with allergic and mixed SA in real clinical practice.Materials and methods. The direct comparative study included SA patients with an allergic component from regional registry of Sverdlovsk region. The data of patients with allergic (n = 68) and mixed (n = 27) SA treated with omalizumab (n = 62) and dupilumab (n = 33) were analyzed. Therapy effectiveness was determined for 12 months in general group No. 1, allergic asthma group No. 2 and mixed asthma group No. 3 according to the following indicators: asthma control level (ACT), proportion of patients with uncontrolled asthma, need for systemic glucocorticosteroids (SGCS) and short‐acting beta agonists (SABA), basic therapy volume, asthma exacerbations number, emergency calls and hospitalizations, forced expiratory volume in the first second (FEV ), assessment of life quality (AQLQ and SNOT-22). Control evaluation visits were conducted before therapy start, after 4 and 12 months of biologics taking.Results. In general, during the 12 months of targeted therapy in patients receiving omalizumab statistically significant positive dynamics was observed in 12 of the 13 evaluated indicators; in patients receiving dupilumab – in 9 indicators. When analyzing such indicators as, ACT, taking SGCS, exacerbations of SA, FEV , statistically significant positive dynamics was revealed for all 4 indicators in patients receiving omalizumab in group No. 2 and in patients receiving dupilumab in group No. 3.Conclusions. Patients with allergic component of SA respond equally well to therapy with omalizumab and dupilumab. At the same time, a tendency towards the advantage of omalizumab in patients with allergic asthma, and dupilumab in patients with a mixed phenotype of the disease was revealed.

Impact of hormonal therapy on HIV-1 immune markers in cis women and gender minorities.

Although sex hormones are recognized to induce immune variations, the effect of hormonal therapy use on immunity is only poorly understood. Here, we quantified how hormonal therapy use affects HIV-1 immune markers in cis women (CW) and trans women and non-binary people (TNBP) with HIV. We considered CD4, CD8 and lymphocyte measurements from cis men (CM), CW and TNBP in the Swiss HIV Cohort Study. We modelled HIV-1 markers using linear mixed-effects models with an interaction between 'gender' (CW, TNBP) and 'hormonal therapy use' (yes/no). Models were adjusted on age, ethnicity, education level, time since start of antiretroviral therapy and use of intravenous drugs. We assessed the inflammatory effect of hormonal therapy use in 31 TNBP using serum proteomics measurements of 92 inflammation markers. We included 54 083 measurements from 3092 CW and 83 TNBP, and 147 230 measurements from 8611 CM. Hormonal therapy use increased CD4 count and CD4:CD8 ratio in TNBP more than in CW (pinteraction = 0.02 and 0.007, respectively). TNBP with hormonal therapy use had significantly higher CD4 counts [median = 772 cells/μL, interquartile range (IQR): 520-1006] than without (617 cells/μL, 426-892). This was similar to the effect of CW versus CM on CD4 T cells. Hormonal therapy use did not affect serum protein concentrations in TNBP. This study highlights the potential role of hormonal therapy use in modulating the immune system among other biological and social factors, especially in TNBP with HIV.

РЕЗУЛЬТАТЫ ПОСЛЕДОВАТЕЛЬНОГО ХИРУРГИЧЕСКОГО ВМЕШАТЕЛЬСТВА И ТЕРАПИИ ИНТЕРФЕРОНАМИ МЕТАСТАЗОВ НЕЙРОЭНДОКРИННОГО РАКА ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ У ПАЦИЕНТКИ С БОЛЕЗНЬЮ ФОН ГИППЕЛЯ-ЛИНДАУ

Abstract. Introduction. The article provides a literature review on the epidemiology, diagnosis, and treatment of neuroendocrine tumors. The morpho-functional classification by WHO 2022 is presented with the division of neuroendocrine tumors into three groups. Justifications are given for the choice of instrumental methods of topical diagnostics and the need for determining universal and specific biochemical markers in blood serum or plasma. The principles are indicated for choosing the advanced methods of treating neuroendocrine tumors. Aim. To review the scientific literature on neuroendocrine tumors, providing our own clinical observations. Materials and Methods. Russian- and English-language literature sources on this disease were searched for in the databases, such as PubMed, Medscape, Cochrane Library, and eLibrary. Clinical case of our female patient V., 36 years old, with von Hippel-Lindau disease (heterozygous mutation R167W of the VHL gene). Results and Discussion. As an example, we describe a clinical case of surgical treatment followed by long-term use of interferons in a female patient with neuroendocrine pancreatic cancer with metastases to the liver and retroperitoneal lymph nodes. Histological examination of the surgical material revealed highly differentiated neuroendocrine cancer with low malignant potential. A screening examination of the genetic syndrome components revealed a heterozygous mutation R167W of the VHL gene. Her survival under treatment exceeded 9.5 years, including more than 4.5 years from the start of interferon therapy. This pathology occurred in a young woman with one of the rare genetic multiorgan hereditary forms of neuroendocrine tumors, Von Hippel-Lindau disease that manifested itself as a combination of benign (retinal angiomatosis of both eyes and adenomas of both adrenal glands) and malignant diseases (pancreatic cancer). Conclusions. The given clinical example demonstrates that in a patient with highly differentiated metastatic pancreatic cancer, after distal subtotal resection of the pancreas, splenectomy, retroperitoneal lymphadenectomy, followed by treatment with interferons, life expectancy was more than 9.5 years, including more than 4.5 years from the start of therapy with interferons only. Despite the numerous side effects of interferons described in the literature, the patient tolerated the treatment well. At the same time, a connection between the hypothyroidism detected in the patient and treatment with interferons cannot be ruled out, since dysfunction of the thyroid gland is one of its side effects.

Do Adolescents with Substance Use Disorders Recognize and Adopt Self-Regulation from Peers? – A Qualitative Interview Study.

Do Adolescents with Substance Use Disorders Recognize and Adopt Self-Regulation from Peers? - A Qualitative Interview Study Self-regulation often plays a central role for adolescents who develop a substance use disorder, as deficits may trigger the onset of the disease. Likewise, the improvement of self-regulation strategies is an important element of many therapy programs. Additionally, peers are important in the development of substance use disorders.The aim of this paper is to investigate the role of self-regulation by other peers in adolescents with substance use disorders through a qualitative interview study. For this purpose, a total of N = 13 (54 % female) adolescents were interviewed using semi-structured interviews, which were then evaluated using a qualitative content analysis according to Mayring.The results showed that the adolescents were familiar with the concept of self-regulation but did not name the interplay between cognitions, emotions, motivation, and behavior within self-regulation. Furthermore, the adolescents reported having observed and adopted both adaptive and maladaptive self-regulation strategies in others, placing the maladaptive strategies retrospectively before the start of therapy, while the adaptive strategies were rather placed during the therapy phase. This might partly explain the effect that peers pose a risk factor for the development of substance use disorders. However, peers might also be considered as a resource in therapeutic settings.