Standard Regimen Research Articles

Anti factor Xa monitoring for venous thromboprophylaxis in severely burn-injured patients: A systematic review

IntroductionPatients with severe burn injuries are at risk of venous thromboembolism (VTE) and associated sequelae. Burn-injured patients may require larger doses of VTE prophylaxis so underdosing may occur with standard regimens. Monitoring anti-factor Xa (AFXa) levels may allow tailoring of dosage but is currently uncommon. The purpose of this systematic review was to methodically review the available literature with respect to AFXa in severe burn-injured patients, and thereby assess its efficacy. MethodsUsing PRISMA guidelines, “Xa” and “burns” were used to systematically review MEDLINE (1946 - present) and EMBASE (1974 - present) databases for publications regarding the monitoring of AFXa levels for thromboprophylaxis in burn-injured patients. ResultsEight studies (432 patients) met inclusion. Peak AFXa level at initial measurement was reported in all studies and was within the range for prophylaxis in 184 of 432 cases (42.6%), below range in 246 of 432 cases (56.9%) and above range for 2/432 (0.5%). Complications were reported in 7 studies (412 patients), with a total of 30 (7.3%) complications, comprising of 16 (53.3%) VTE events and 14 (46.7%) mortalities. Three studies comprising 270 patients compared complications between patients who were within the reference range with patients who were below the range. There were 164 patients from the ‘within the reference range’ groups that had a total of 6 (3.7%) complications, comprised of 4 (66.7%) VTE events and 2 (33.3%) mortalities. There were 106 patients from the ‘below reference range group’ that had a total of 11 (10.4%) complications, comprised of 9 (81.8%) VTE events and 2 (18.2%) mortalities. ConclusionOur findings suggest standard prophylactic anticoagulation dosing risks underdosing and therefore, an increased risk in the development of VTE. AFXa monitoring allows individually tailored dose adjustment to reach therapeutic levels, which may be efficacious in reducing VTE events and is therefore recommended where possible.

Cyclic strain promotes MCP-1 expression in Dahl Salt Sensitive (SS) rat vascular smooth muscle cells (VSMCs) through the TGF-β pathway

Prior studies have suggested a role for TGF-β in the generation of hypertension in SS rats. We have shown that production of MCP-1 (CCL-2) and TGF-β1 increase in the vasculature of hypertensive SS rats. This study aims to explore novel mechanisms of hypertension development. We hypothesize that TGF-β1 regulated the production of MCP-1 by VSMCs in the setting of cyclic strain. Primary cultures of SS aortic VSMCs in early (<6) passages were grown in standard fashion in Dulbecco’s Modified Eagle’s Medium supplemented with 10% fetal bovine serum. Cultured cells were identified as smooth muscle cells by their characteristic morphology and positive immunostaining for α-smooth muscle actin. In the first study, VSMCs were treated with recombinant active TGF-β1 (1 ng/mL and 10 ng/mL) for 6 h, then harvested for MCP-1 mRNA quantification by SYBR green qPCR. Medium was also collected to determine MCP-1 levels using ELISA. TGF-β1 increased MCP-1 mRNA expression by 2.0- and 3.1-fold in VSMC incubated in medium containing 1 ng/mL and 10 ng/mL of TGF-β1, respectively. In a second series of studies, VSMCs were seeded onto 6-well BioFlex plates. Some cells were pre-treated with 10 μmol/mL of an ALK4/5 inhibitor. Cyclic strain, an in vitro model of hypertension, was performed using the FlexCell 6000 and a standardized regimen (8 h, 15% elongation @ 1 Hz). Cells and medium were then harvested for mRNA analyses and determination of MCP-1 levels. When compared with expression by VSMCs maintained under static condition, cyclic strain increased (p<0.05) MCP-1 mRNA expression 4.2-fold and TGF-β1 mRNA 1.93-fold. Cyclic strain also increased (p<0.01) MCP-1 protein in the medium (static condition vs cyclic strain, 112.6 ± 7.1 pg/mL vs 222.5 ± 6.5 pg/mL, n=6). Pre-treatment of VSMC with the ALK4/5 inhibitor reduced mRNA expression of MCP-1 mediated by cyclic strain (Cyclic strain vs Cyclic strain + AKL4/5 inhibitor, 4.5 ± 1.06 vs 2.88 ± 0.47, n=6, P < 0.01). Thus, cyclic strain promotes MCP-1 production by VSMCs through the TGF-β pathway. The data support the need for further study of this interaction as well as a potential role in arterial hypertension in this rodent model. Department of Veterans Affairs Basic Sciences R&D (BSRD) Service (1 I01 BX005640) National Institutes of Health (P30 DK079337). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Probiotic formulations and gastro-intestinal diseases in the paediatric population: a narrative review.

Probiotics are live microbial supplements that improve the microbial balance in the host animal when administered in adequate amounts. They play an important role in relieving symptoms of many diseases associated with gastrointestinal tract, for example, in necrotizing enterocolitis (NEC), antibiotic-associated diarrhea, relapsing Clostridium difficile colitis, Helicobacter pylori infections, and inflammatory bowel disease (IBD). In this narrative review, the authors aim to evaluate the role of different probiotic formulations in treating gastrointestinal diseases in pediatric population aged 18 years or younger and highlight the main considerations for selecting probiotic formulations for use in this population. The authors searched PubMed and Clinicaltrials.gov from inception to 24th July 2022, without any restrictions. Using an iterative process, the authors subsequently added papers through hand-searching citations contained within retrieved articles and relevant systematic reviews and meta-analyses. The effectiveness of single-organism and composite probiotics in treating gastrointestinal disorders in pediatric patients aged 18 or under were analyzed and compared in this study. A total of 39 studies were reviewed and categorized based on positive and negative outcomes, and compared with a placebo, resulting in 25 studies for single-organism and 14 studies for composite probiotics. Gastrointestinal disorders studied included NEC, acute gastroenteritis (AGE), Acute Diarrhea, Ulcerative Colitis (UC), and others. The results show that probiotics are effective in treating various gastrointestinal disorders in children under 18, with single-organism probiotics demonstrating significant positive outcomes in most studies, and composite probiotics showing positive outcomes in all studies analyzed, with a low incidence of negative outcomes for both types. This study concludes that single-organism and composite probiotics are effective complementary therapies for treating gastrointestinal disorders in the pediatric population. Hence, healthcare professionals should consider using probiotics in standard treatment regimens, and educating guardians can enhance the benefits of probiotic therapy. Further research is recommended to identify the optimal strains and dosages for specific conditions and demographics. The integration of probiotics in clinical practice and ongoing research can contribute to reducing the incidence and severity of gastrointestinal disorders in pediatric patients.

T-cell recruiting immunotherapies in B-cell lymphoma - the future backbone for all therapy lines?

The introduction of immunologically targeted therapies has represented a significant advancement in the treatment of B-cell lymphomas, particularly aggressive B-cell lymphoma. CD19 CAR-T cells such as Axicabtagen-Ciloleucel (Axi-cel) and Lisocabtagen Maraleucel (Liso-cel) have been approved since 2022 and 2023, respectively, for second-line therapy of Diffuse Large B-Cell Lymphomas (DLBCL), when there is primary refractory disease or relapse within 12 months after the end of first-line therapy. These therapies result in a significant improvement in progression-free survival compared to the previous standard therapy (salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation). Especially in elderly patients or patients with underlying medical conditions, CAR-T cell therapies like Axi-cel and Liso-cel demonstrate acceptable tolerability and high efficacy.Furthermore, bispecific T-cell-engaging antibodies ("bispecifics") such as Glofitamab, Epcoritamab, and Mosunetuzumab also represent promising treatment options for patients with relapsed disease after failure of second- or later line therapy and show efficacy even in a subset of patients relapsing after CD19 CAR-T cells. However, randomized study results for these substances are not yet available. They are expected to be used in earlier lines of therapy in the future, especially in combination with standard chemotherapy regimens. Common side effects of bispecific antibody therapies are cytokine release syndrome (CRS) and immune-mediated cytopenias, whereas immune-cell associated neurotoxicity syndrome (ICANS) is relatively rare compared to CD19 CAR T cells. In summary, bispecifics represent a novel, highly effective immunotherapy for the treatment of lymphomas with a very favourable toxicity profile.

Whole-course quality of tuberculosis (TB) care in rural China: a retrospective study based on chart abstraction

ObjectivesThe aim of this study was to assess the quality of tuberculosis (TB) care for the whole course and assess factors that affect completing treatment.DesignThis is an observational retrospective study...

Pneumocystis jirovecii Pneumonia in a Liver Transplant Recipient With an Adverse Reaction to Trimethoprim/Sulfamethoxazole Treated With a Sulfonamide Desensitization Protocol: Case Report

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that, in immunocompromised patients, can progress to respiratory failure and death. Since trimethoprim/sulfamethoxazole (TMP/SMX) chemoprophylaxis has become a standard management, the prognosis has improved. However, there are patients with a history of TMP/SMX intolerance who cannot receive chemoprophylaxis. We report on a 53-year-old male liver recipient treated with a standard triple immunosuppressive regimen in whom TMP/SMX was waived because of a history of allergy manifested as a generalized rash with edema more than 30 years ago. At transplantation, the immunologic risk was assessed as low, and liver graft function was normal. In the third month after engraftment, he developed dyspnea at rest required constant passive oxygen therapy. Ceftriaxone, azithromycin, and clindamycin were implemented. Mycophenolate acid was stopped, and tacrolimus was reduced. High-resolution computed tomography revealed interstitial pneumonia. Pneumocystis jirovecii pneumoniae was diagnosed from bronchoalveolar lavage. Instead of TMP/SMX, pentamidine and caspofungin were also used for PJP, with no improvement. After 3 weeks, the patient deteriorated. Because of his life-threatening condition, TMP/SMX was introduced in the sulfonamide desensitization protocol, including hydrocortisone and clemastinum. Within 4 days, the patient stabilized with no signs of TMP/SMX intolerance. Pneumonia subsided within a month, and TMP/SMX was prescribed lifelong. Prophylaxis for PJP with TMP/SMX still remains an important issue in transplant recipients. Adverse reaction to TMP/SMX in the past is not always a contraindication to reintroducing prophylaxis. The decision of prophylaxis avoidance should be analyzed carefully; in uncertain cases, a sulfonamide desensitization protocol should be considered.

Влияние режима пожара на огнестойкость несущих строительных конструкций машинных залов ГРЭС

Machine rooms of a state district power plant (GRES) are sizeable. Heat impact on the structures of the building in the case of a real fire can significantly differ from the impact in the case of a standard fire. Therefore, the calculation of fire resistance of building structures should be conducted not only in conditions of a standard fire but of a real fire as well. The objective of the study is the theoretical evaluation of the actual limits of fire resistance of load-bearing building structures of the machine room of the main building of the Nizhneturinskaya GRES in conditions of standard and real fire regimes. Numerical experiments to calculate the heating of load-bearing building structures in the case of a standard fire and the case of the most hazardous scenario of the real fire development have been conducted in the framework of the study. A field 3-dimensional model to calculate fire hazardous factors and a non-stationary thermal conductivity equation have been applied. The obtained results have been analyzed. The field model adapted to the space-planning solutions of the machine room has been described. The most hazardous scenario of the development of real fire in case of combustion of the turbine oil spill in the sector of the machine room with the lowest height of ceiling has been chosen. The temperature fields in the gaseous environment of the machine room at different moments are presented. It has been detected that the heating of reinforced concrete structures of the machine room ceiling is significantly uneven due to the 3-dimensional gas dynamic pattern of fire. Dependencies of temperatures of the frame of reinforced concrete load-bearing structures of the ceiling on the time of standard and real fires in the most heated section of the ceiling have been obtained. It has been determined that the maximum temperature of the frame in the case of the standard fire is lower than in the case of real fire. Due to the features of the 3-dimensional thermal gas dynamic pattern of fire in machine rooms of the GRES, the fire resistance of load-bearing building structures in these premises must be determined in both conditions of standard fire and real fire, considering the most hazardous scenario of its development.

Adjuvant and post-recurrent treatment patterns in patients with resectable gastric cancer in Japan: a retrospective database cohort study

BackgroundThis study examined temporal shifts in adjuvant therapy patterns in Japanese patients with resectable gastric cancer (GC) and treatment patterns of first-line and subsequent therapy among those with recurrent disease.MethodsThis retrospective analysis of hospital-based administrative claims data (April 1, 2008 to March 31, 2022) included adults (aged ≥ 20 years) with GC who started adjuvant therapy on or after October 1, 2008 (adjuvant cohort) and patients in the adjuvant cohort with disease recurrence (recurrent cohort), further defined by the time to recurrence (≤ 180 or > 180 days after adjuvant therapy).ResultsIn the adjuvant cohort (n = 17,062), the most common regimen during October 2008–May 2016 was tegafur/gimeracil/oteracil potassium (S-1; 95.7%). As new standard adjuvant regimen options were established, adjuvant S-1 use decreased to 65.0% and fluoropyrimidine plus oxaliplatin or docetaxel plus S-1 use increased to 15.0% and 20.0%, respectively, in September 2019–March 2022. In the recurrent cohort with no history of trastuzumab/trastuzumab deruxtecan treatment (n = 1257), the most common first-line regimens were paclitaxel plus ramucirumab (34.0%), capecitabine plus oxaliplatin (CapeOX; 17.0%), and nab-paclitaxel plus ramucirumab (10.1%) in patients with early recurrence, and S-1 plus oxaliplatin (26.3%), S-1 plus cisplatin (15.3%), CapeOX (14.0%), S-1 (13.2%), and paclitaxel plus ramucirumab (10.8%) in those with late recurrence.ConclusionsThis study demonstrated temporal shifts in adjuvant treatment patterns that followed the establishment of novel regimens, and confirmed that post-recurrent treatment patterns were consistent with the Japanese Gastric Cancer Association guideline recommendations.

Maintenance electroconvulsive therapy: An effective yet underused treatment modality in psychiatry: A case series

Maintenance Electroconvulsive Therapy (M-ECT) refers to ECTs administered beyond 6 months after the remission of illness. Maintenance electroconvulsive therapy (M-ECT) can be used to reduce the risk for relapse and recurrence of illness in patients who fare poorly with standard medication regimens. There is improvement in the relapse rate of major psychiatric disorders when continuation or maintenance (C or M-ECT) are used with psychotropics. These are single-center, retrospective case studies of patients diagnosed with major psychiatric disorders (as per International Classification of Diseases, 11th edition) who are receiving M-ECT in Department of Psychiatry, B.J. Government Medical College and Sassoon Hospital, Pune. We included 12 patients- 8 males and 4 females in this study. 4 cases were of patients suffering from schizophrenia, 3 cases were of patients suffering from depression, 1 case of bipolar affective disorder and 4 cases of patients of intellectual disability with psychosis. There was a reduction in hospitalization rate for acute exacerbation and significant improvement in the patients’ overall functioning on standardized rating scales without any significant adverse effects. Maintenance ECT is an underused treatment option that can substantially reduce risks of relapse in patients with major depressive disorder, bipolar disorder and schizophrenia as well. Despite the potential value of these ECT schedules, these are relatively neglected in clinical practice. This article aims to explore the clinical utility of maintenance ECTs and emphasizes the use of maintenance ECTs in routine psychiatric care.

Comparative Analysis of Physical Therapy Outcomes in Acute Ischemic and Hemorrhagic Stroke Rehabilitation

Background: Stroke rehabilitation demands an effective therapeutic approach to enhance functional recovery. This study aims to compare the outcomes of physical therapy in patients with acute ischemic and hemorrhagic stroke using the Motor Relearning Programme (MRP). Methodology: Based on stroke type, confirmed via CT thirty-eight participants were stratified into ischemic & hemorrhagic stroke group. Eligible participants were over 35 years old, had a Glasgow Coma Scale score above 5, and presented with hemiplegia. Exclusion criteria included trauma-induced hemorrhage, cerebellar or brainstem stroke, severe cognitive impairment, or pre-existing disabilities. The participants underwent a standardized four-week physiotherapy regimen based on the MRP, with assessments using the Motor Assessment Scale (MAS) and Functional Independence Measure (FIM) to evaluate the outcomes. Results: These results underscore the significant improvements in the functional outcomes observed in both ischemic and hemorrhagic stroke patients following physical therapy, with hemorrhagic stroke patients showing more substantial gains in both MAS and FIM scores. Conclusion: Our study contributes to a nuanced understanding of stroke rehabilitation, emphasizing that while both ischemic and hemorrhagic stroke patients significantly benefit from structured physical therapy interventions like MRP, the specifics of their recovery processes vary.

Комбинированная терапия воспалительных заболеваний придатков матки как альтернатива стандартным схемам лечения

Цель исследования. Показать преимущество комбинированной терапии (озонотерапия и бактериофаготерапия) по сравнению со стандартными схемами в лечении хронических воспалительных заболеваний придатков матки. Материалы и методы. В исследование были включены 300 пациенток с хроническими воспалительными заболеваниями придатков матки (ХВЗПМ) в период обострения (хронический сальпингоофорит). Они были поделены на 2 группы по 150 человек: основную группу и группу контроля. Каждая пациентка в обеих группах сдавала посев на микрофлору из цервикального канала с определением чувствительности к антибиотикам и бактериофагам. Пациенткам из основной группы проводили озонотерапию (внутриматочное промывание 800 мл озонированного физиологического раствора с концентрацией озона 5000 мг/л, а также внутривенное капельное введение 250 мл озонированного физиологического раствора с концентрацией озона 1200 мг/л), после озонотерапии проводилось промывание полости матки 20 мл бактериофага, а заканчивалось все установкой ватного тампона, смоченного 5 мл бактериофага, в задний свод влагалища. Данные процедуры проводились 1 раз в день в течение 10 дней. Пациентки же из контрольной группы получали антибиотикотерапию препаратами, соответствующими возбудителям, а также противовоспалительную терапию (диклофенак 3,0 в/м 1 р/д и метронидазол 250 мг по 1 таблетке 3 раза в день). Данная схема применялась также в течение 10 дней. Оценку клеточного иммунитета проводили методом непрямой иммунофлюоресценции моноклональными антителами. Результаты. Показатель CD3+ лимфоцитов в основной группе до лечения – 49,2±0,6% (после лечения – 59,9±0,8%), в контрольной группе – 50,2±0,7% (после лечения – 59,7±0,3%). Уровень CD4+ до лечения в основной группе – 38,8±1,2% (после лечения – 44,9±1,2%), в контрольной – 37,7±1,4% (после лечения – 33,5±1,0%). Исходный уровень CD8+ лимфоцитов в основной группе – 33,3±0,4% (после лечения – 25,5±0,5%), в контрольной группе – 31,8±0,9% (после лечения – 30,3±0,8%). Иммунорегуляторный индекс в основной группе до лечения – 1,16±0,07 (после лечения – 1,76±0,04), в контрольной группе – 1,18±0,06 (после лечения – 1,1±0,07). Заключение. На основании полученных данных исследования было доказано преимущество комбинированной терапии (озонотерапия и бактериофаготерапия) по сравнению со стандартными схемами в лечении хронических воспалительных заболеваний придатков матки. Purpose of the study. Demonstrate the advantage of combined therapy (ozone therapy and bacteriophage therapy) compared to standard protocols in the treatment of chronic inflammatory diseases of the uterine appendages. Materials and methods. The study included 300 patients with chronic inflammatory diseases of the uterine appendages (chronic salpingo-oophoritis) during exacerbation. They were divided into two groups of 150 individuals each: the main group and the control group. Each patient in both groups underwent a microbial culture test from the cervical canal, with sensitivity testing to antibiotics and bacteriophages. Patients in the main group received ozone therapy (intrauterine lavage with 800 ml of ozone-treated physiological solution with an ozone concentration of 5000 mg/L, as well as intravenous drip infusion of 250 ml of ozone-treated physiological solution with an ozone concentration of 1200 mg/L). After ozone therapy, uterine cavity lavage with 20 ml of bacteriophage was performed, followed by the placement of a cotton swab soaked in 5 ml of bacteriophage in the posterior fornix of the vagina. These procedures were performed once a day for 10 days. Patients in the control group received antibiotic therapy corresponding to the identified pathogens, as well as anti-inflammatory therapy (diclofenac 3.0 intramuscularly once a day and metronidazole 250 mg orally 3 times a day). This regimen was also applied for 10 days. Cellular immunity was assessed by indirect immunofluorescence with monoclonal antibodies. Results. CD3+ lymphocyte levels in the main group before treatment were 49.2% ± 0.6% (after treatment – 59.9% ± 0.8%), in the control group – 50.2% ± 0.7% (after treatment – 59.7% ± 0.3%). The CD4+ level before treatment in the main group was 38.8% ± 1.2% (after treatment – 44.9% ± 1.2%), in the control group – 37.7% ± 1.4% (after treatment – 33.5% ± 1.0%). The initial level of CD8+ lymphocytes in the main group was 33.3% ± 0.4% (after treatment – 25.5% ± 0.5%), in the control group – 31.8% ± 0.9% (after treatment – 30.3% ± 0.8%). The immunoregulatory index in the main group before treatment was 1.16±0.07 (after treatment – 1.76±0.04), in the control group – 1.18±0.06 (after treatment – 1.1±0.07). Conclusion. Based on the obtained research data, the advantage of combined therapy (ozone therapy and bacteriophage therapy) over standard protocols in the treatment of chronic inflammatory diseases of the uterine appendages has been demonstrated.

Successful treatment of recurrent visceral leishmaniasis relapse in an immunocompetent adult female with functional hypopituitarism in Bangladesh.

Currently available treatment options are mostly effective in achieving long-term cure in visceral leishmaniasis (VL) patients. However, there have been reports of recurrence of this illness in both immunosuppressed and immunocompetent patients. We report the first case of recurrent VL relapse in a 19-year-old immunocompetent female with functional hypopituitarism (hypogonadotropic hypogonadism with central hypothyroidism) from Bangladesh, who has been treated three times previously with optimal dosage and duration- liposomal amphotericin B (LAmB) alone and in combination with miltefosine. We treated the patient successfully with a modified treatment regimen of 10 mg/kg body weight LAmB for two consecutive days along with oral miltefosine for seven days as loading dose. For secondary prophylaxis, the patient received 3 mg/kg body weight LAmB along with oral miltefosine for seven days monthly for five doses followed by hormonal replacement. The patient remained relapse free after 12 months of her treatment completion. In the absence of protective vaccines against Leishmania species and standard treatment regimen, this modified treatment regimen could help the management of recurrent relapse cases.

Daratumumab and venetoclax combined with CAGE for late R/R T-ALL/LBL patients: Single-arm, open-label, phase I study.

The prognosis of patients diagnosed with relapsed or refractory (R/R) T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has consistently been unsatisfactory, with limited treatment options. As reports, the CAG regimen can serve as a salvage treatment for R/R T-ALL/LBL, but there remains a subset of patients who do not benefit from it. Recent studies have indicated that daratumumab (Dara) and venetoclax (Ven) may offer promising therapeutic benefits for T-ALL/LBL. In light of these findings, we conducted a safety and efficacy evaluation of the enhanced treatment regimen, combining Dara and Ven with aclarubicin, cytarabine, granulocyte colony-stimulating factor, and etoposide (CAGE), in patients suffering from R/R T-ALL/LBL. The participants in this phase I trial were patients with R/R T-ALL/LBL who fail to standard treatment regimens. During each 28-day cycle, the patients were treated by Dara, Ven, cytarabine, aclarubicin, granulocyte colony-stimulating factor, etoposide. The primary endpoint of this study was the rate of remission. This report presents the prospective outcomes of 21 patients who received the salvage therapy of Dara and Ven combined with the CAGE regimen (Dara + Ven + CAGE). The objective remission rate (ORR) was determined to be 57.1%, while the complete remission (CR) rate was 47.6%. Notably, patients with the early T-cell precursor (ETP) subtype exhibited a significantly higher remission rate in the bone marrow compared to non-ETP patients (100% vs. 44.4%, p = 0.044). The Dara + Ven + CAGE regimen demonstrated a favorable remission rate in patients with R/R T-ALL/LBL. Moreover, the treatment was well-tolerated.

Maintenance Therapy for CD20+ Indolent Lymphoma: Who Should Receive Maintenance?

Maintenance rituximab (MR) has been a mainstay of treatment in Canada for CD20‑positive indolent lymphoma for two decades. The adoption of MR into clinical practice occurred after the publication of the EORTC 20981 trial. This trial showed a significant improvement in progression free survival (PFS) with two years of MR versus observation after induction therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with relapsed follicular lymphoma (FL). The use of MR was broadly extended to include its use in the front‑line setting, following any R-containing inductions and including all CD20-positive indolent lymphoma histologies. Automatic recommendations for MR became the standard practice for most patients. Given the recent changes to standard induction regimens in some indications, and with heightened concerns about infectious complications during B-cell depleting therapy, the recommendation for the use of MR should no longer be considered automatic. This review offers a balanced perspective of the evidence for MR.

Method for obtaining ecological products from rainbow trout Oncorhynchus mykiss farming

In aquaculture, the period of active development of aquatic organisms is considered one of the most important for the formation of potential in the future. The issue of using natural components when growing aquatic organisms and feeding young fish is given special attention. This research investigated Spirulina (25%) + Vermiculture (50%) + Hermetia illucens (25%) as an additional source of functional active substances and protein that affect the body performance of rainbow trout in early ontogenesis. All objects were cultured in a special bioreactor, which was a component of the recirculating aquaculture model system as well as in the laboratory, where an installation was made for cultivating natural food. The results of the scientific and practical part of the work showed that after the end of the experiment, body weight was higher in the experimental fish by 7.2% than in the control group. This article presents the results of feeding rainbow trout as one of the cases of improving the morpho-functional and biochemical composition of the blood of this species: an increase in the total number of red blood cells by 11.0%, hemoglobin content by 9.7%, total protein at 22.7%, albumin by 24.2%, and creatinine by 15.5%, compared with the control group. The presented positive changes in the functional status of the rainbow trout organism were in harmony with the parameters of body weight, as well as histological indicators. Histological indicators of the liver and muscle tissue of the fish supplemented the obtained positive result of the influence of natural and active components of the feed. Feeding fish according to the scheme in the experimental group promotes the formation of layers of special adipose tissue in the endomysium. The total amount of the stromal component in the muscle tissue of rainbow trout was 25% of the mass of the entire tissue. The control group showed that the muscle fibers were polygonal in cross section, separated from each other within the bundle by delicate layers of endomysium. When using a standard feeding regimen (control group), the stromal component is a moderately expanding structure that replaces the space between the fibers. The experimental group had the most significant indicators. The intensification of individual aspects of homeostasis achieved with the help of feed components (experimental group) promotes the growth of muscle fibers in thickness due to the formation of new fibrils, but not an increase in the proportion of sarcoplasm (watery meat). As a result, neurohumoral regulation and substance synthesis processes improved in the fishes’ body, which helps to improve ontogenesis rates. The presented ingredients in the diet of rainbow trout are natural stimulants of metabolic processes and sources of nutrients. The method allows aquaculture to be defined as being as close as possible to “environmentally safe”. The next stage will be a comprehensive analysis of the qualitative and quantitative characteristics of rainbow trout meat under the influence of the feed factor.

Quantifying the effect of surrounding spatial heterogeneity on land surface temperature based on local climate zones using mutual information

Local climate zone (LCZ), a landscape classification scheme that segments urban region into 17 distinct zones, has become the standard for analyzing urban thermal environments since 2012. The characteristic features of each LCZ decide the standard regime for their Land Surface Temperature (LST). In heterogeneous cities, the variation in LST is observed for similar but spatially dispersed LCZs and has not yet been analysed by the researchers. The surrounding spatial heterogeneity could be partially responsible for such variation. Hence, we have presented a framework to analyze the LST variation of similar but spatially dispersed LCZs by considering the surrounding LCZ pattern11LCZ pattern represents the group of LCZs surrounding any considered LCZ.details in the study area of Nagpur (India). The framework uses machine learning techniques like random forest (RF), Xgboost, deep learning to confirm that the LST variation is due to surrounding LCZ pattern. Later it indentifies the factors responsible for LST variation in each LCZ type using our proposed mutual information based Adjacent LCZ preference Estimator (ALPE). Deep learning model captures 90–92 % of the neighbourhood heterogeneity responsible for LST variation as compared to RF (0.83- 0.79) and Xgboost (0.86–0.81). The reduction in bias (by 1.05 °C -1.39 °C) is observed while estimating LST incorporating surrounding LCZ pattern. This confirms that the external heterogeneity affects the LST of the corresponding LCZ. Further, the result analysis of ALPE suggests that characteristics of open LCZ types (when they are present in surrounding) highly influence the LST of compact and open LCZs.

Environmentally safe installation for determining the fire resistance of coatings and fire resistance tests of small fragments building structures

Actuality. Taking into account fire statistics, the task of preventing the occurrence and spread of fires is urgent. It is obvious that the fire resistance of building structures, which must be taken into account at the design stage, is of the greatest importance and influence on the development and spread of fires in buildings and structures. Conducting fire experiments makes it possible to obtain the most complete information about the behavior of building structures under fire effects, however, the scale of field tests, labor-intensiveness, energy consumption and damage to the environment prompts the search and development of alternative methods that would ensure the environmental friendliness of the tests, compliance with the conditions of the experiment ( standard fire temperature regime), and at the same time would make it possible to estimate the limit of fire resistance of a building structure in reduced dimensions or to experimentally determine the fire-resistant ability (efficiency) of fire-resistant coatings. Purpose. The main goal of the article is rationale use of an installation for determining the fire-resistant capacity (efficiency) of fire-resistant coatings and fire resistance tests of small-sized fragments of building structures, taking into account the reduction of the harmful load on the environment. Main results. Research has been carried out and the design features of the installation have been substantiated, the principle of which is to heat the inner space of the chamber with the help of electric heating elements, which, unlike liquid fuel (diesel fuel, fuel oil, gas), do not harm the environment. A control unit-module of variable voltage regulation designed to regulate the heating temperature of the radiation panel in the test chamber has been developed. The design of the created test setup makes it possible to increase or decrease the temperature on the heating surface of the test sample, not only with the help of the heating temperature regulator, but also in manual mode, by moving the test sample closer or further away from the radiation panel along the guides. Conclusions. According to the results of experimental tests, it was established that the chamber of the installation warms up uniformly and according to the standardized temperature-time dependence Ts = 345lg (8t+1)+20). At the same time, the temperature regulation process using BP-10 with triac output ensures stable operation of electric heating elements up to temperatures of 1000 °C. A feature of the created installation is the possibility of additional lowering or raising of the temperature on the heating surface of the experimental sample, in case of its deviation during the experiment, by means of approaching or moving away from the sample to the heating panel. The conducted studies confirm the necessary reproducibility of experimental results.

Rituximab in Childhood and Juvenile Pemphigus Vulgaris: A Systematic Review.

Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion, affecting the skin and mucous membranes. Both males and females are affected, although it predominantly affects females in their fifth and sixth decades of life. Approximately 1.4 to 3.7% of PV cases occur in the pediatric population (≤18 years of age), and may be classified into childhood/pediatric PV, which affects individuals under 12 years old, and juvenile/adolescent PV, affecting those between 12 and 18 years old. Due to its rare occurrence in children and adolescents, there is often a delay in diagnosis and treatment in this age group. A systematic literature search was conducted on MEDLINE/PubMed, Web of Science, EMBASE, SCOPUS, and Cochrane Library databases to evaluate the efficacy of rituximab (RTX) in childhood and juvenile PV patients. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was employed to assess the risk of bias in case reports and series, while the Cochrane ROBINS-I tool was utilized for evaluating observational studies or non-randomized intervention studies. A total of 18 studies encompassing 46 juvenile or childhood PV patients in the pediatric and adolescent age groups were included for qualitative synthesis. The studies included nine case reports, two case series, five retrospective studies, one prospective study, and one open-label pilot study. Almost all cases of childhood and juvenile PV achieved either complete or partial remission after undergoing RTX treatment during the final follow-up periods. Furthermore, most cases reported no relapse, and only minor adverse events were noted in the RTX treatment group. Despite its potential benefits, the utilization of RTX in pediatric patients raises concerns due to the scarcity of evidence and the absence of controlled studies specific to this age group. Further exploration is necessary to establish a standardized treatment regimen for RTX in pediatric PV, which involves identifying the optimal dosage, frequency, treatment cycle duration, and maintenance therapy duration.

Practice diffusion in China’s two-pronged engagement in global technical standardization

In the context of intensifying geopolitical rivalry, China’s transition from rule-taker to rule-maker in technical standard-setting has generated deep contention with established stakeholders in the Global North. This article analyses how China, as a latecomer to global technical standardization, has navigated this increasingly contested arena of global economic governance. Building on the ‘practice turn’ literature in International Relations and a conceptualization of standard-setting processes as shaped by ‘communities of practice’, this article argues that ‘practice diffusion’ is of crucial significance for China’s rising standards power. Just as it sees mastery of global standardization practice as a key dimension of increasing its influence in established standards developing organizations, China has also begun to diffuse its standardization practice abroad in the effort to lay the foundations of a China-centric standardization regime. The article develops this argument by identifying four specific mechanisms of practice diffusion – learning the basics, learning to lead, learning within the region, learning to build – and by illustrating the role that each has played in Chinese stakeholders’ evolving engagement in global technical standard-setting.

Comprehensive Therapeutic Approaches to Tuberculous Meningitis: Pharmacokinetics, Combined Dosing, and Advanced Intrathecal Therapies.

Tuberculous meningitis (TBM) presents a critical neurologic emergency characterized by high mortality and morbidity rates, necessitating immediate therapeutic intervention, often ahead of definitive microbiological and molecular diagnoses. The primary hurdle in effective TBM treatment is the blood-brain barrier (BBB), which significantly restricts the delivery of anti-tuberculous medications to the central nervous system (CNS), leading to subtherapeutic drug levels and poor treatment outcomes. The standard regimen for initial TBM treatment frequently falls short, followed by adverse side effects, vasculitis, and hydrocephalus, driving the condition toward a refractory state. To overcome this obstacle, intrathecal (IT) sustained release of anti-TB medication emerges as a promising approach. This method enables a steady, uninterrupted, and prolonged release of medication directly into the cerebrospinal fluid (CSF), thus preventing systemic side effects by limiting drug exposure to the rest of the body. Our review diligently investigates the existing literature and treatment methodologies, aiming to highlight their shortcomings. As part of our enhanced strategy for sustained IT anti-TB delivery, we particularly seek to explore the utilization of nanoparticle-infused hydrogels containing isoniazid (INH) and rifampicin (RIF), alongside osmotic pump usage, as innovative treatments for TBM. This comprehensive review delineates an optimized framework for the management of TBM, including an integrated approach that combines pharmacokinetic insights, concomitant drug administration strategies, and the latest advancements in IT and intraventricular (IVT) therapy for CNS infections. By proposing a multifaceted treatment strategy, this analysis aims to enhance the clinical outcomes for TBM patients, highlighting the critical role of targeted drug delivery in overcoming the formidable challenges presented by the blood-brain barrier and the complex pathophysiology of TBM.