Development Of Serious Adverse Events Research Articles

Patients with atrial fibrillation in outpatient practice: clinical characteristics and outcomes over a 10-year observation period (data from the REQUAZA AF registrу — Yaroslavl)

Aim. To present clinical characteristics and assess serious adverse outcomes (death, acute cardiovascular events) in outpatients with atrial fibrillation (AF) in one of the Yaroslavl clinics for 10 years.Material and methods. A total of 212 patients with AF aged from 23 to 94 years were included in the REQUAZA AF registrу — Yaroslavl at the first visit to the clinic in 2013. Their health status was monitored over 10,5 years through in-person visits, phone contacts with patients, their relatives, and treating physicians. Recorded data included the AF type, comorbid conditions, extent and quality of examinations and treatments, development of serious adverse events, and mortality. Statistical processing was carried out using the Microsoft Office 365 application software package.Results. Most patients (66,5%) were diagnosed with persistent AF. Paroxysmal, persistent, and newly detected forms were observed in 26,4%, 3,8%, and 3,3% of patients, respectively. Most AF patients had concomitant cardiovascular diseases, most frequently hypertension (96,7%), heart failure (91,6%), and coronary artery disease (91,2%). A total of 54 patients (25,5%) had prior stroke or transient ischemic attack. Complete information was obtained for 203 patients (95,8%), of which 164 (78,5%) passed away during the follow-up period. The leading death cause was cardiovascular disease, particularly cerebrovascular events (n=111; 67,7%). The highest mortality was recorded within the first two years of follow-up, during which more than a quarter (25,1%) of the registered patients had died. The COVID-19 pandemic did not significantly affect the mortality rates. The most common AF complications were stroke and transient ischemic attack, with a total of 74 episodes in the history and follow-up period, including 7 recurrences.Conclusion. Ambulatory AF patients represent a group with a high frequency of cardiovascular events and fatal outcomes. In the observed group of ambulatory AF patients, annual mortality exceeded 10%, and over 3/4 of patients died within 10 years. The leading death cause was cardiovascular disease, primarily cerebrovascular events.

Anticancer Properties of Mexican Medicinal Plants: An Updated Review

Mexico is considered a mega-diverse country due to its terrestrial, marine, and biological richness. Throughout history, Mexican medicinal plants have been used to elaborate decoctions, pastes, and powders to treat neoplastic, gastrointestinal, metabolic, neurodegenerative, skin, and infectious disorders. Cancer constitutes a group of diseases that result from the uncontrolled growth and proliferation of cells. Current treatment regimens against it encompass the administration of chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Despite their possible efficacy, their use is often related to the possibility of relapse, the development of serious adverse events, toxic effects, and many drug-resistance mechanisms. As an alternative, Mexican medicinal plants have been extensively studied using their capacity to elicit strong anticancer activities and possess novel bioactive and safe compounds. This review concentrates on the knowledge gained in recent years (2011–2022) about the anticancer properties of extracts and isolated compounds from Mexican medicinal plants. Generalities, antioxidant activities, features of cancer cells, and drug-resistance mechanisms are reviewed in this work. In addition, the possible anticancer mechanisms of isolated compounds and the status of FDA-approved cancer drugs derived from plants are covered. Finally, our perspective on the future of traditional medicine and Mexican medicinal plants in cancer treatment is presented.

Antitumor activity of solution of natural substance G-01 at the example of sarcoma M-1 without adjuvant available.

Objective. To study the properties of the solution G-01 in a single injection while changing the concentration of the solution.
 Materials and methods. The monosaccharide hexose was used as a means of exposing animals. Working code: G-01. The animals were divided into 5 groups: group 1 10 rats (who received a 10 % solution of G-01 sc, once), group 2 10 rats (who received a 15 % solution of G-01 sc, once), group 3 10 rats (who received a 20 % solution of G-01 sc, once), group 4 10 rats (who received a 25 % solution of G-01 sc, once), group 5 10 rats (control group did not receive G-01 solutions in various concentrations).
 Results. During the observation of animals, after transplanting a suspension of tumor cells, the growth of a solid tumor was detected in 100 % of cases in rats of the control group. In the experimental groups, in which 10 % and 25 % G-01 solution was used, the growth of solid tumors was also detected. Moreover, the growth rate and volume of tumors, visually, did not differ in the groups. In rats, who received a 15 % solution of G-01, a tumor developed in 3 out of 10 rats. In rats, who received a 20 % solution of G-01 in 2 out of 10 rats.
 Conclusions. The results of the work carried out prove that the substance of natural origin G-01 is a generator of adaptive immunity for the prevention of the development of the tumor process. In case of the development of the disease, it allows to achieve a tumor regression without the development of serious adverse events affecting the quality of life of animals, that is the main goal of antitumor treatment or prevention of any oncological disease.

Reactogenicity of various COVID-19 vaccination regimens

During the spread of an increasing number of new variants of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), it is extremely important not only to assess the immunogenicity and efficacy, butalso the safety of various combinations of vaccines. Excessive immune response and associated signs and symptoms may occur with varying frequency as expected from the use of vaccines.Aim. To compare the reactogenicity of various (heterologous and homologous) vaccination regimens in a prospective observational study.Material and methods. In individuals aged ≥18 years, in the absence of contraindications to vaccination, two types of vaccines were used at primary vaccination and revaccination: Gam-COVID-Vac and CoviVac: group I (n=97) — Gam-COVID-Vac at each stage of primary and booster vaccination ; group II (n=7) — Gam-COVID-Vck at each stage of primary vaccination, CoviVac at each stage of revaccination; group III (n=42) — CoviVac at each stage of primary vaccination, Gam-COVID-Vac at each stage of revaccination; group IV (n=38) — CoviVac at each stage of primary and secondary vaccination. In all participants, the dynamics of IgG to SARS-CoV-2 spike glycoprotein receptor-binding domain and T-cell immunity to SARS-CoV-2 were determined over time. To control the plasma hemostasis, the method of dynamic thrombophotometry was used. Local and systemic adverse events were assessed.Results. The number of vaccinated individuals with a rise in body temperature above 370 C after the 1st stage of revaccination was significantly (p<0,05) more in group I (37,5%) and group II (57,1%) compared with vaccinated persons of IV group. At the same time, after the 2nd stage of revaccination, in general, a smaller percentage of vaccinated persons with hyperthermia was noted. In group I, a higher percentage of persons (22,9%) complaining of the appearance of weakness after stage I of revaccination was noted compared to vaccinated persons of group IV — 5,2%. An increase in the fibrin clot growth rate was noted in group III at the stage of revaccination.Conclusion. The use of various revaccination schemes (homologous and heterologous) was not associated with the development of serious adverse events. The resulting local and systemic reactions were shortlived and did not require hospitalization. More pronounced systemic reactions were noted in the form of a short-term fever and weakness when using the Gam-COVID-Vac. No cases of arterial or venous thrombosis were registered during the follow-up period.

Real-world effectiveness and safety of pan-genotypic antiviral therapy for chronic HCV-infection: data from three clinical centers in St. Petersburg

The aim of the analysis was to describe the results of administration of pan-genotype antiviral therapy (glecaprevir / pibrentasvir, GLE / PIB) in real-world setting in three clinical centers in St. Petersburg within the city program for the treatment of chronic hepatitis C. Materials and methods. A retrospective analysis of the GLE / PIB usage of in the period from 2019 to 2022 within the city program for the treatment of chronic hepatitis C in St. Petersburg was carried out. Results. The analysis included 464 patients treated in three clinical centers of St. Petersburg: St. Petersburg State Medical Institution “Clinical Infectious Diseases Hospital named after S. P. Botkin”, St. Petersburg State Medical Institution “Center for the Prevention and Control of AIDS and Infectious Diseases” and the Clinic of Infectious Diseases of the Military Medical Academy named after S. M.Kirov”. Overall 452 out of 464 patients (97 %) achieved SVR12. According to the duration of treatment, SVR12 rates were the following: 8 weeks – 97.7 % (419 / 429), 12 weeks – 92.9 % (26 / 28) and 16 weeks – 100 % (7 / 7). The effectiveness according to fibrosis stage was as follows: F0 – 97 % (142 / 146), F1 – 100 % (74 / 74), F2 – 100 % (59 / 59), F3 – 98 % (57 / 58), F4 (CP-A, B) – 94 % (118 / 125). SVR12 according to HCV genotypes and subtypes was the following: genotype 1b – 100 % (63 / 63), genotype 1a – 91 % (21 / 23), genotype 1 unspecified – 100 % (23 / 23), genotype 2 – 98 % (50 / 51), genotype 3 – 97 % (292 / 301). In patients with an indeterminate genotype, the efficacy was 100 % (7 / 7). Antiviral therapy was well tolerated, there were no cases of discontinuation of therapy, as well as cases of the development of serious adverse events. Conclusion. GLE / PIB has demonstrated high effectiveness in the real-world setting in patients infected with prevalent genotypes of HCV, including those with genotype 3 and compensated liver cirrhosis. The results of our analysis fully correspond to the data obtained earlier in clinical trials andreal-world setting.

Could inadvertent intravenous injection of COVID-19 vaccines cause severe adverse events?

The emergence and rapid spread of COVID-19 led to the development of novel vaccines to fight against the disease. Although COVID-19 vaccines are the major key to controlling the disease and have a good safety profile, they may be associated with some adverse events. Recently, a few studies noted that inadvertent incorrect injection of COVID-19 vaccines may lead to the development of serious adverse events. Herein, we report a case of inadvertent intravenous COVID-19 vaccine injection who developed severe anaphylactic shock following receiving the COVID-19 vaccine. Proper vaccine injection technique training may help to reduce the risk of developing adverse events and improve vaccine safety and efficacy.

Systematic treatment and prevention of cardiac digoxin toxicity

Digoxin has a narrow therapeutic index, such as complicated pharmacokinetics and dynamics. Many drug interactions may occur when the administration of one drug alters the clinical effects of another. As a result, digoxin toxicity can be a common condition within clinical settings that might lead to the development of many morbidities and even mortality. Many studies were published to investigate the efficacy and safety of different management modalities to enhance the outcomes that follow digoxin administration. The aim of the study was to discuss the approaches to systematically treat and prevent the development of cardiac digoxin toxicity. The findings are based on evidence from previous studies in the literature. To be specific, Fab fragments are the most effective modalities that can be used to treat severe cases within ideal periods. However, evidence regarding their administration for asymptomatic or mild cases is still poor regarding the cost-efficacy and the development of serious adverse events. Physicians should primarily care for a better intervention as it is usually associated with a significantly more enhanced prognosis and clinical outcomes. Nevertheless, adequate monitoring of the patients and evaluation of their personal and medical history are important steps in the process, and further approaches are still needed. Also, detailed information about our intended outcomes is furtherly discussed within the manuscript.

Oral PI3K-δ,γ Inhibitor for the Management of People with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: A Narrative Review on Duvelisib.

The development of highly effective targeted therapies has led to a new treatment paradigm in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). Despite these advances, many patients will eventually require alternative treatment strategies due to the emergence of tolerability issues or resistance to these novel agents. Duvelisib is a first-in-class, potent oral agent with dual inhibitor activity against the δ and γ isoforms of phosphoinositide 3-kinase (PI3Kδ and PI3Kγ), which are specific to the hematopoietic system. Dysregulation of the PI3K/PTEN/AKT/mTOR pathway has been implicated in cancer cell growth, survival and metabolism and has been the subject of cancer drug development in recent years. Duvelisib demonstrated activity in CLL/SLL in early trials, leading to further evaluation in the Phase 3 DUO trial that compared duvelisib against ofatumumab in patients with relapsed/refractory CLL/SLL. This trial led to the Food and Drug Administration (FDA) approval for the treatment of adult patients with CLL/SLL after at least two prior lines of therapy. The major reason for therapy discontinuation is the development of serious adverse events, which include severe infections and diarrhea/colitis, precluding its widespread use. Ongoing clinical trials are evaluating duvelisib in combination strategies and with alternate dosing schedules in patients with CLL/SLL. With close monitoring, duvelisib can be a promising drug for the treatment of patients with relapsed or refractory CLL/SLL. This review summarizes the relevant clinical data from recent clinical advances in CLL and aims to interpret the duvelisib trials while exploring strategies to improve its use and adverse event management in the era of novel targeted agents.

Long-term Follow-up of treatment of chronic foot wounds with recombinant human epidermal growth factor in patients with different complications of diabetes mellitus

BACKGROUND: Diabetic foot ulcer (DFU) is a dangerous complication of diabetes mellitus (DM), which can lead to the development of chronic wounds and amputations. Recombinant human epidermal growth factor (rhEGF) can be used as an adjuvant treatment for chronic wounds resistant to standard treatment. Studies have demonstrated its clinical efficacy, however, there is insufficient information on the long-term results of treatment, its safety and the effect on the progression of diabetes complications, adverse cardiovascular events and the development of cancer.AIM: To assess the long-term results of rhEGF therapy for trophic foot ulcers in individuals with multiple complications of diabetes.METHODS: The study included 20 patients with type 1 and type 2 diabetes and various forms of DFS without critical ischemia, who had previously been treated with DFS using rhEGF in order to assess the general condition, progression of microand macrovascular complications of diabetes, adverse cardiovascular events, the development of cancer and the quality of life.RESULTS: There was a statistically significant difference between the area of wound defects, the percentage of granulation tissue that filled the wound defect, before the start of rhEGF treatment and at the time of discharge from the hospital (p <0.05). During treatment with rhEGF, mild adverse events were observed in 35%. Complete epithelialization of wounds in most patients occurred in 3 [2; 4] months. In 11.76%, the wound was not completely epithelialized. Relapse occurred in 5.8% due to non-compliance with limb unloading. Minor amputation was performed in 1 patient. Progression of diabetic retinoand nephropathy was revealed in 23.5%. 11.76% suffered myocardial infarction of unknown age, 1 patient (5.88%) suffered acute cerebrovascular accident. Serious adverse events in the form of PE with a fatal outcome and critical ischemia of the lower limb were recorded in 5.8%.CONCLUSIONS: As a result of the study of long-term results of rhEGF treatment of chronic foot wounds, a low percentage of relapses and small amputations, the absence of high amputations and oncological diseases, the development of serious adverse events in 2 patients, the progression of diabetic retinoand nephropathy in 4 patients, the development of IM of unknown age in 2 patients was recorded. and stroke in 1 patient after rhEGF therapy.

Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis

BACKGROUND & AIMS:We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice.METHODS:A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients were treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist–naïve and –exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately.RESULTS:A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab- treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229–2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135–2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496–5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist–naïve and –exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502–1.612) or serious infections (HR, 1.235; 95% CI, 0.608–2.511) between vedolizumab-treated and TNF antagonist–treated patients. However, in TNF-antagonist–naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049–0.754).CONCLUSIONS:Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist–naïve patients.

Neuroinflammation after SCI: Current Insights and Therapeutic Potential of Intravenous Immunoglobulin.

Traumatic spinal cord injury (SCI) elicits a complex cascade of cellular and molecular inflammatory events. Although certain aspects of the inflammatory response are essential to wound healing and repair, post-SCI inflammation is, on balance, thought to be detrimental to recovery by causing "bystander damage" and the spread of pathology into spared but vulnerable regions of the spinal cord. Much of the research to date has therefore focused on understanding the inflammatory drivers of secondary tissue loss after SCI, to define therapeutic targets and positively modulate this response. Numerous experimental studies have demonstrated that modulation of the inflammatory response to SCI can indeed lead to significant neuroprotection and improved recovery. However, it is now also recognized that broadscale immunosuppression is not necessarily beneficial and may even carry the risk of contributing to the development of serious adverse events. Immune modulation rather than suppression is therefore now considered a more promising approach to target harmful post-traumatic inflammation following a major neurotraumatic event such as SCI. One promising immunomodulatory agent is intravenous immunoglobulin (IVIG), a plasma product that contains mostly immunoglobulin G (IgG) from thousands of healthy donors. IVIG is currently already widely used to treat a range of autoimmune diseases, but recent studies have found that it also holds great promise for treating acute neurological conditions, including SCI. This review provides an overview of the inflammatory response to SCI, immunomodulatory approaches that are currently in clinical trials, proposed mechanisms of action for IVIG therapy, and the putative relevance of these in the context of neurotraumatic events.

Adverse Event Risk Assessment on Patients Receiving Combination Antiretroviral Therapy in South Africa

Purpose: To determine the risk factors for the development of serious adverse events (AEs) in black adult patients on combination antiretroviral therapy (cART). Methods: This prospective cohort study consisted of 368 adult black HIV positive patients receiving cART at the Grey’s Hospital, KwaZulu-Natal, South Africa. Patients were intensively monitored for incidence of adverse events and the factors associated with their development, under the Antiretroviral Cohort Adverse Event Monitoring in KwaZulu-Natal (ACADEMIK). Multiple logistic regression models were used to identify the risk factors for AEs. Results: A total of 406 AEs were reported across the 13 patient hospital visits in the study. Peripheral neuropathy was the most prevalent adverse event (16%), followed by hypercholesterolaemia (14%), lipoatrophy/lipodystrophy (13%) and skin reaction (11%). Cluster differentiation (CD4) counts (p = 0.0280), age (p = 0.0227) and weight (p = 0.0017) were identified as the significant predictors for hypercholesterolaemia, while sex (p = 0.0309) was significant with respect to skin reaction. CD4 counts (p=0.0200) was also significant for lipoatrophy/lipodystrophy. Skin reaction (23%), diarrhea (18%), hypercholesterolaemia (15%), thrombocytopenia (15%) and peripheral neuropathy (13%) were the top five most incident AEs. Overall, about 46% of the regimens administered were tenofovir-based and 31% zidovudine-based. Conclusions: To enhance the prevention of hypercholesterolaemia, lipoatrophy/lipodystrophy and skin reaction among black adult HIV positive patients on cART, we recommend that CD4 counts and weight be closely monitored and documented during clinic visits.

Effectiveness and safety of narlaprevir in real clinical practice of chronic hepatitis C

Objective: to analyze the efficacy and safety of using direct antiviral action drug narlaprevir/ritonavir in combination with the prolonged alpha-interferon and ribavirin drugs in the conditions of day-time hospitals of St. Petersburg and. Novgorod. Materials and methods : The study included. 35 patients with CHC of the 1st genotype. For treating these patients, a three-component regimen was used, which included the use of narlaprevir/ritonavir in combination, with peg-interferon and ribavirin. Results: among all patients included, in the study, a sustained, virological response was noted, in 85,7%. Early virological response was observed, in 91,3% cases. The recurrence rate was observed, in 10% patients. In 3 patients, therapy was interrupted, for the following reasons: due to inefficiency, the development of serious adverse events, and on its own initiative. Conclusion: the data obtained, demonstrate high, virological and. clinical efficacy and. safety of narlaprevir in combination with peg-interferon and ribavirin, in the treatment of chronic viral hepatitis C.

The Study of the Fixed Dose Combination of Lisinopril with Prolonged Indopamide (FIXLINDA) with Daily Blood Pressure Monitoring and Diuresis in Hypertensive Patients

Аim. To study the efficacy, tolerability and safety of using a fixed dose combination of an ACE inhibitor lisinopril with a prolonged-action diuretic indapamide in patients with degree 1-2 hypertension.Material and methods. Patients (n = 32) with uncontrolled 1-2 degrees hypertension, moderate or high cardiovascular risk, without severe comorbid diseases, who were prescribed a fixed dose combination of lisinopril (5, 10 or 20 mg) and indapamide (1.5 mg) were included in the observational study. All patients had home monitoring of blood pressure and diuresis, as well as assessment of subjective tolerance of treatment and registration of adverse events within 3 months of observation. Assessment of changes in circadian fluctuations in blood pressure and diuresis, the frequency of achieving the target blood pressure at the outpatient stage, as well as the subjective tolerance of treatment and adverse events during a three-month follow-up.Results. Target blood pressure was achieved in 44.5% of patients taking the fixed dose combination of lisinopril 5 mg + prolonged-acting indapamide1.5 mg; 76.9% – in patients taking the combination of lisinopril 10 mg + indapamide 1.5 mg; 78,6% – in patients taking the combination of lisinopril 20 mg + indapamide 1.5 mg. The achieved antihypertensive effect was characterized by daily circadian stability, accompanied by an improvement in the initially impaired day and night diuretic profile (increase in the share of daytime diuresis by 29.6% and 22.3% with a decrease in the share of nighttime diuresis by 35% and 49% when using a combination with lisinopril 5 and 10 mg, respectively). The treatment was well tolerated by patients and did not cause the development of serious adverse events. Reported adverse events (non-intense dry cough, headache, general weakness) were transient and did not require correction or withdrawal of treatment.Conclusion. The fixed dose combination of the ACE inhibitor lisinopril (5, 10 or 20 mg) and the long-acting thiazide-like diuretic indapamide (1.5 mg) had good antihypertensive efficacy with improved circadian blood pressure and diuresis profiles, acceptable tolerance and safety of treatment, as well as a simple choice of doses of the drug components.

Predictors of toxicity-related hospitalization in four randomized studies of 5-fluorouracil-based chemotherapy in metastatic colorectal cancer.

To evaluate the predictors of toxicity-related hospitalization associated with various chemotherapy regimens among metastatic colorectal cancer patients METHODS: This pooled analysis includes patient-level datasets from four randomized clinical studies (NCT00272051; NCT00305188; NCT00115765; NCT00364013). Through univariate and multivariate logistic regression analyses, factors predicting the development of serious adverse events, fatal adverse events, and toxicity-related hospitalizations were determined. A total of 2533 patients were included in the current study. A total of 1010 patients (39.9%) experienced one or more episodes of serious adverse events. These include 914 patients (36.1%) who were hospitalized at least once and 148 patients (5.8%) who suffered from a fatal adverse event. Within multivariate logistic regression analysis, older age (P < 0.001), higher ECOG score (P < 0.001), bevacizumab-containing chemotherapy (P < 0.001), and panitumumab-containing chemotherapy (P < 0.001) were predictive of hospitalization. Similarly, older age (P < 0.001), higher ECOG score (P < 0.001), and panitumumab-containing chemotherapy (P = 0.003) were predictive of fatal adverse events in multivariate logistic regression analysis. Moreover, in a multivariate Cox regression analysis, hospitalization was predictive of worse overall survival (P < 0.001) and progression-free survival (P < 0.001). Older age, poorer performance status, and bevacizumab- and panitumumab-containing regimens are associated with a higher risk of hospitalization. Moreover, hospitalization is predictive of worse overall and progression-free survival.

Cytokines as therapeutic targets in primary Sjögren syndrome.

Primary Sjögren syndrome (SjS) is a systemic autoimmune disease that may affect 1 in 1000 people (overwhelmingly women) and that can be a serious disease with excess mortality due to severe organ-specific involvements and the development of B cell lymphoma; systemic involvement clearly marks the disease prognosis, and strongly suggests the need for closer follow-up and more robust therapeutic management. Therapy is established according to the organ involved and severity. As a rule, the management of systemic SjS should be organ-specific, with glucocorticoids and immunosuppressive agents limited to potentially-severe involvements; unfortunately, the limited evidence available for these drugs, together with the potential development of serious adverse events, makes solid therapeutic recommendations difficult. The emergence of biological therapies has increased the therapeutic armamentarium available to treat primary SjS. Biologics currently used in SjS patients are used off-label and are overwhelmingly agents targeting B cells, but the most recent studies are moving on into the evaluation of targeting specific cytokines involved in the SjS pathogenesis. The most recent etiopathogenic advances in SjS are shedding some light in the search for new highly-selective biological therapies without the adverse effects of the standard drugs currently used (corticosteroids and immunosuppressant drugs). This review summarizes the potential pharmacotherapeutic options targeting the main cytokine families involved in the etiopathogenesis of primary SjS and analyzes potential insights for developing new therapies.

Efficacy and safety of endoscopic submucosal dissection for submucosal tumors of the colon and rectum

Endoscopic submucosal dissection (ESD) of colorectal submucosal tumors (SMTs) is becoming increasingly common; however, there have been few large consecutive studies analyzing its therapeutic efficacy and safety. The aim of this study was to evaluate the efficacy, safety, and long-term outcomes of ESD for colorectal SMTs. This retrospective study included 412 consecutive patients with colorectal SMTs who underwent ESD at the Zhongshan Hospital of Fudan University from January 2008 to July 2014. Tumor histopathology, completeness of resection, adverse events, tumor recurrence, and distant metastasis were analyzed. Complete resection was achieved for 358 lesions (86.9%). Thirteen patients had serious adverse events (3.2%) including bleeding and perforation, and 28 patients (6.8%) had post-ESD electrocoagulation syndrome (PEECS). Because more ESDs for colorectal SMTs were performed by endoscopists, the rate of complete resection increased (78.5% vs 88.5%), and the rate of serious adverse events decreased (9.2% vs 2.0%). SMTs in the colon increased the risk of incomplete resection (19.6% vs 11.3%), serious adverse events (8.7% vs 1.6%), and PEECS (16.3% vs 4.1%). SMTs originating from the muscularis propria and sized≥20mm increased the rate of PEECS (22.7% vs 5.9% and 31.3% vs 5.8%, respectively). ESD is effective for resection of colorectal SMTs and rarely causes serious adverse events. Tumor location and the experience of endoscopists influence the complete resection rate and the development of serious adverse events. ESD is feasible for large tumors and tumors in the muscularis propria, but this is associated with relatively high risks of adverse events.

Immunization With a Pneumococcal Polysaccharide Vaccine in Children With Juvenile Idiopathic Arthritis Without Systemic Manifestations: a Prospective Study

Background . Patients with juvenile idiopathic arthritis (JIA) have an increased risk of being infected. Approximately half of all serious infections in children with JIA are associated with airway involvement. Objective . Our aim was to study the efficacy and safety of the pneumococcal 13-valent conjugate vaccine (PCV) in children with JIA. Methods. In a prospective cohort study, 5 groups were formed: children with JIA in the remission phase on methotrexate therapy (group 1) or etanercept (group 2), with JIA in the active phase prior to the appointment of methotrexate (group 3) or etanercept (group 4), control group (conditionally healthy children). 0.5 ml of the 13-valent PCV was administered once subcutaneously during therapy in patients in the remission phase or 3 weeks before the appointment of methotrexate or etanercept in patients in the active phase. The main study outcome was the proportion of patients with a protective ( 40 mg/L) level of specific anti-pneumococcal antibodies (anti-SPP) IgG to Streptococcus pneumoniae 4 weeks after vaccination. In addition, we assessed the incidence of infectious events before and after vaccination as well as changes in the content of a high-sensitivity C-reactive protein, S100 protein, and post-vaccination period. Results. The study included 125 children. Four weeks after vaccination, the protective level of anti-SPP IgG was established in 21 (84%) patients in the 1st, 23 (92%) in the 2nd, 22 (88%) in the 3rd, 24 (96%) in the 4th and 5th groups (p =1.0). Increase in the concentration of S100 protein and high-sensitivity C-reactive protein after vaccination was not noted. JIA exacerbation episodes were not recorded in any patient. After immunization, the total number of infectious events decreased in all observed groups (p 0.001). Serious adverse events were not registered during the study. Conclusion . Vaccination with the 13-valent PCV in children with JIA is highly effective and is not accompanied by the development of serious adverse events.

The Salford Lung Study is a way to improve asthma control in real clinical practice (a review)

The Salford Lung Study in asthma (SLS-Asthma) is the first prospective, randomized, controlled clinical trial conducted in conditions and in population that were very close to real clinical practice. The study demonstrated that treatment of a large heterogeneous population of asthma patients using combination of vilanterol (VI) and fluticasone furoate (FF) (22/92 mg q.d. or 22/184 mg q.d.) via Ellipta dry powder inhaler provided better control of the disease than the conventional therapy administered by an attendant physician. The level of asthma control in VI/FF group was consistently maintained for 12 months with no identified change in risk of development of serious adverse events. Results were similar in patients receiving ICS or ICS/LABA combinations and did not depend on smoking status or number of exacerbations over the previous year.

Efficacy and Safety of Immunization With Pneumococcal Polysaccharide Vaccine in Children With Juvenile Idiopathic Arthritis: Preliminary Results of a Prospective Open-Label Study

Juvenile idiopathic arthritis (JIA) is one of the most frequent and most disabling rheumatic diseases in children. Children with JIA receiving immunosuppressive and genetically engineered biologic drugs belong to the high-risk group for the development of bacterial and viral infections, including those administered by preventive vaccines. Objective: Our aim was to evaluate the efficacy and safety of 13-valent pneumococcal polysaccharide vaccine (PPV) in children with JIA. Methods. In a prospective open-label comparative study, the efficacy of vaccination was determined by the level of specific anti-pneumococcal antibodies (anti-SPP)IgG to Streptococcus pneumonia in the blood serum in patients with JIA. The safety of vaccination was assessed by determining a high-sensitivity C-reactive protein and S-100 protein as well as by the number of adverse events, by recording the number of infections of the upper respiratory tract and pneumonias, by the number of joints with active arthritis. Vaccination with 13-valent PPV was performed subcutaneously with one dose of 0.5 ml during therapy of the main disease with methotrexate or etanercept or 3 weeks before the appointment of methotrexate or etanercept. Patients were followed up for 1 year. Results. The study included 42 children with JIA: 21 with JIA in the active phase of the disease, 21 in remission of the disease. As a result of vaccination, the level of anti-pneumococcal antibodies (antiSPP)IgG increased in the group of children with JIA in the active phase from 26.1 (14.3; 52.1) to 73.0 (52.5; 156.0) mg/l (p = 0.001), with JIA in remission — from 27.4 (18.2; 59.1) to 54.6 (35.3; 96.0) mg/l (p = 0.029). The concentration of the predictor of S-100 protein high activity after vaccination was not increased (p = 0.192). JIA aggravation episodes were not fixed in any patient. Serious adverse events were not observed during the trial. Conclusion. The vaccination of children with JIA with 13-valent PPV is highly effective, not accompanied by exacerbation/increase in the activity of the disease and the development of serious adverse events.