Dysfunction Syndrome Research Articles

Symptoms 6 months following SARS-CoV-2 infection in Nepali women.

In Nepal, over 1 million individuals have tested positive for SARS-CoV-2. We sought to describe the frequency of nonrecovery from this infection at 6 months and associated symptoms. We conducted a retrospective cohort study of 6142 women who had positive and negative PCR tests for this infection 6 months previously at 3 institutions in Kathmandu. In telephone interviews women provided information on 22 symptoms and their intensities, health status and history, and functional status. Of 3732 women who had tested PCR positive, 630 (16.9%) reported that they were unrecovered. These 630 unrecovered women were distinguished statistically from the 3102 recovered women by more frequent histories of allergies, rheumatoid disease, BCG immunization, Covid vaccination, strep throat and recent URIs, and both weight gain and weight losses of more than 5 kg in the 6 months following testing, and stressful events in the preceding year. Fatigue, pain, difficulty remembering, shortness of breath, heat and cold intolerance and unrefreshing sleep were reported in 41.9% to 10.5% of these 630 unrecovered women. Six months after confirmed SARS-CoV-2 infection 16.9% of Nepali women have long-COVID manifested as an immune, metabolic, and hormonal systems disruptive and dysfunction syndrome.

The International Society of Thrombosis and Hemostasis (ISTH) criteria in intensive care units

Disseminated Intravascular Coagulation (DIC) has been assessed by the International Society of Thrombosis and Hemostasis (ISTH) 2001 and the ISTH 2018-modified version. More investigations are needed to assess usability and visibility of those DIC scoring systems in the intensive care units (ICU). This study investigated the predictive performance of the ISTH-Overt DIC versions of 28-day mortality in ICUs compared to SOFA as a gold standard assessment tool of sepsis. A retrospective design (2015-2017) included 220 adult patients enrolled from medical and surgical ICUs in two major hospitals in Jordan. We calculated ISTH-Overt DIC scores and SOFA score on time of DIC diagnosis. Overt DIC was categorized based on a score of ≥ five for ISTH DIC 2001; and ≥ 4 for ISTH DIC 2018. Provided, a score > 12 was categorized as Multiple-Organ- Dysfunction-Syndrome (MODS) for Sequential Organ Failure Assessment (SOFA) score. Then, 28-day mortality follow-up was performed. More than half of sample died before 28-days of follow-up. The analysis of Receiver Operating Characteristic (ROC) showed that higher scores of ISTH DIC 2001(≥ 5), ISTH DIC 2018 (≥ 4), and SOFA score (>12) were highly associated with 28-day mortality. The ISTH DIC 2001 and SOFA score were superior on the modified ISTH 2018 in predicting 28-day mortality, with an Area Under the Curve (AUC) of (0.724 vs. 0.822 vs. 0.507, respectively). Yet, the accuracy of the SOFA score was better than the ISTH DIC 2001. This study suggests that ISTH DIC 2001 score is helpful when applied on medical and surgical ICU Jordanian populations. It showed better results compared to the Modified ISTH DIC 2018 in mortality prediction, regardless of the underlying diseases.

Framing depression as a functional signal, not a disease: Rationale and initial randomized controlled trial

Depression is often framed as a disease or dysfunctional syndrome, yet this framing has unintended negative consequences including increased stigma. Here, we consider an alternative messaging framework - that depression serves an adaptive function. We describe the historical development of popular messages about depression and draw from the fields of evolutionary psychiatry and social cognition to describe the alternative framework that depression is a "signal" that serves a purpose. We then present data from a pre-registered, online randomized-controlled study in which participants with self-reported depression histories viewed a series of videos that explained depression as a "disease like any other" with known biopsychosocial risk factors (BPS condition), or as a signal that serves an adaptive function (Signal condition). In the entire sample (N=877), three of the six hypotheses were supported: The Signal condition led to less self-stigma, greater offset efficacy, and more adaptive beliefs about depression. Exploratory analyses revealed these Signal effects were stronger among females (N=553), who also showed a greater growth mindset of depression after the Signal explanation. Results suggest that framing depression as an adaptive signal can benefit patients and avoid harmful consequences of popular etiological presentations. We conclude that alternative framings of depression are worthy of further study.

Daphnoretin relieves IL-1β-mediated chondrocytes apoptosis via repressing endoplasmic reticulum stress and NLRP3 inflammasome

BackgroundOsteoarthritis (OA), mainly caused by severe joint degeneration, is often accompanied by joint pain and dysfunction syndrome. Inflammatory mediators and apoptosis play key roles in the evolution of OA. It is reported that daphnoretin has significant antiviral and anti-tumor values. The present study aims at investigating the role of daphnoretin in OA.MethodsThe OA mouse model was constructed by performing the destabilization of the medial meniscus through surgery, and the OA cell model was induced in ATDC5 chondrocytes with IL-1β (10 ng/mL) in vitro. Chondrocyte viability and apoptosis were measured by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), Caspase-3 activity, and flow cytometry. The levels of COX-2, iNOS, TNF-α, IL-6, Bax, Bcl2, cleaved-Caspase3, endoplasmic reticulum stress (ERS) proteins (GRP78, CHOP, ATF6, and Caspase-12), and NLRP3-ASC-Caspase1 inflammasome were determined by quantitative real-time PCR or western blot. The concentrations of TNF-α, IL-6, and PGE2 were tested by enzyme-linked immunosorbent assay. The content of nitrates was detected by the Griess method. In vivo, morphologic differences in knee joint sections and the thickness of the subchondral bone density plate in mice were observed by hematoxylin–eosin (H&E) staining and safranin O-fast green staining.ResultsDaphnoretin effectively choked IL-1β-induced chondrocyte apoptosis and facilitated cell viability. Daphnoretin dose-dependently abated ERS, inflammatory mediators, and the activation of NLRP3 inflammasomes in IL-1β-induced chondrocytes. What’s more, in vivo experiments confirmed that daphnoretin alleviated OA progression in a murine OA model by mitigating inflammation and ERS.ConclusionDaphnoretin alleviated IL-1β-induced chondrocyte apoptosis by hindering ERS and NLRP3 inflammasome.Graphical abstract

P-046: FACTORS ASSOCIATED WITH LEG ULCERS IN CAMEROONIAN SICKLE CELL DISEASE PATIENTS

Purpose: Leg ulcers are the most common skin complication in sickle cell patients. Though it is associated with great morbidity and cost of care, research is rather sparse on this condition. Through this study, we wished to determine the factors associated with leg ulcers in sickle cell patients in two hospitals in Douala. Materials and methods: This was a retrospective cross-sectional study carried out over a period of 05 years (January 01, 2015 to December 31, 2019). This study was carried out at two sites: the outpatient hematology department of the General Hospital Douala and Sickle cell care center at the Laquintinie hospital Douala. We included all sickle cell patients aged 10 years and above. We excluded patients with incomplete files. Data on sociodemographic characteristics and clinical parameters were collected. Analysis was done using SPSS version 25.0 software. Qualitative variables were compared using Pearson’s chi-square test. Multivariate analysis was done using logistic regression to determine the factors associated with leg ulcers. Significance level was set at p <0.05. Results: Out of 620 sickle cell patients, 41 (6.6%) had a leg ulcer. The median age of patients with a leg ulcer was 28 years (IQR 22-33). The male to female sex ratio was 1.15. Leg ulcers were traumatic in 70.7% of cases. The leg ulcer was unique in 65.85% (n=27) and located next to the malleolus in 26 (63.34%) of patients. Sociodemographic characteristics significantly associated with leg ulcers were the age groups 30-39 years [OR=9.3 (3.1-27.3), p <0.001], 20-29 years [6.3 (2.3-17.1), p <0.001] and a history of leg ulcer [2.7 (1.1-6.4), p=0.020]. For clinical characteristics, pulmonary hypertension [3.5 (1.7-6.7), p<0.001] and aseptic osteonecrosis of the femoral head [1.5 (0.01-2.25), p=0.020] were significantly associated with leg ulcers. Conclusion: In the pathogenesis of leg ulcer, a triad of mechanical obstruction of the microcirculation, hémolysis-vascular dysfunction syndrome and venous incompetence has been incriminated. in our study, one out of fifteen patients with sickle cell disease in Douala has a leg ulcer. Factors associated with leg ulcers were age between 20-39 years, pulmonary hypertension, aseptic osteonecrosis of the femoral head and history of leg ulcer. These factors are probably the result of chronic hyperhemolysis in our population. The authors do not declare any conflict of interest

MR lymphangiography of lymphatic abnormalities in children and adults with Noonan syndrome

Noonan syndrome is associated with complex lymphatic abnormalities. We report dynamic-contrast enhanced MR lymphangiography (DCMRL) findings in children and adults with Noonan syndrome to further elucidate this complex disease spectrum. A retrospective evaluation of patients with confirmed Noonan syndrome and clinical signs of lymphatic dysfunction undergoing DCMRL between 01/2019 and 04/2021 was performed. MRL included T2-weighted imaging (T2w) and DCMRL. Clinical history/presentation and genetic variants were recorded. T2w-imaging was evaluated for central lymphatic abnormalities and edema distribution. DCMRL was evaluated regarding the presence of cisterna chyli/thoracic duct, lymphatic leakages, pathological lymphatic reflux and abnormal lymphatic perfusion. The time from start of contrast-injection to initial enhancement of the thoracic duct venous junction was measured to calculate the speed of contrast propagation. Eleven patients with Noonan syndrome with lymphatic abnormalities (5 female, 6 male; 7 infants, 4 adults; mean age 10.8 ± 16.4 years) were identified (PTPN11 n = 5/11 [45.5%], RIT1 n = 5/11 [45.5%], KRAS n = 1/11 [9%]). Patients had a chylothorax (n = 10/11 [91%]) and/or pulmonary lymphangiectasia [dilated pulmonary lymph vessels] (n = 9/11 [82%]). Mediastinal/pulmonary edema was depicted in 9/11 (82%) patients. The thoracic duct (TD) was (partially) absent in 10/11 (91%) cases. DCMRL showed lymphatic reflux into intercostal (n = 11/11 [100%]), mediastinal (n = 9/11 [82%]), peribronchial (n = 8/11 [73%]), peripheral (n = 5/11 [45.5%]) and genital lymphatics (n = 4/11 [36%]). Abnormal pulmonary/pleural lymphatic perfusion was seen in 8/11 patients (73%). At infancy peripheral/genital edema was more prevalent in patients with RIT1 than PTPN11 (n = 3/5 vs. n = 0/5). Compared to patients with PTPN11 who had fast lymphatic enhancement in 4/5 patients, enhancement took markedly longer in 4/5 patients with RIT1-mutations. Thoracic duct dysplasia, intercostal reflux and pulmonary/pleural lymphatic perfusion are characteristic findings in patients with Noonan syndrome presenting with chylothorax and/or pulmonary lymphangiectasia. Central lymphatic flow abnormalities show possible phenotypical differences between PTPN11 and RIT1-mutations.

Phenotypes of Motor Deficit and Pain after Experimental Spinal Cord Injury.

Motor disability is a common outcome of spinal cord injury (SCI). The recovery of motor function after injury depends on the severity of neurotrauma; motor deficit can be reversible, at least partially, due to the innate tissue capability to recover, which, however, deteriorates with age. Pain is often a comorbidity of injury, although its prediction remains poor. It is largely unknown whether pain can attend motor dysfunction. Here, we implemented SCI for modelling severe and moderate neurotrauma and monitored SCI rats for up to 5 months post-injury to determine the profiles of both motor deficit and nociceptive sensitivity. Our data showed that motor dysfunction remained persistent after a moderate SCI in older animals (5-month-old); however, there were two populations among young SCI rats (1 month-old) whose motor deficit either declined or exacerbated even more over 4–5 weeks after identical injury. All young SCI rats displayed changed nociceptive sensitivity in thermal and mechanical modalities. The regression analysis of the changes revealed a population trend with respect to hyper- or hyposensitivity/motor deficit. Together, our data describe the phenotypes of motor deficit and pain, the two severe complications of neurotrauma. Our findings also suggest the predictability of motor dysfunction and pain syndromes following SCI that can be a hallmark for long-term rehabilitation and recovery after injury.

Multi‐organ dysfunction syndrome in patients undergoing extracorporeal life support

Multiple organ failure is a common complication in patients undergoing ECLS significantly affecting patient outcomes. Gaining knowledge about the mechanisms of onset, clinical course, risk factors, and potential therapeutic targets is highly desirable. Data of 354 patients undergoing ECLS with one-, two, three-, and four organ failures were retrospectively analyzed. Incidence of multiple organ dysfunction (MODS), its impact on survival, risk factors for its occurrence, and the impact of proinflammatory mediators on the occurrence of MODS in patients undergoing ECLS were investigated. The median follow-up was 66 (IQR 6; 820) days. 245 (69.2%) patients could be weaned from ECLS, 30-day survival and 1-year survival were 194 (54.1%) and 157 (44.4%), respectively. The duration of mechanical support was 4 (IQR 2; 7) days in the median. Increasing severity of MODS resulted in significant prolongation of mechanical circulatory support and worsening of the outcome. Liver dysfunction had the strongest impact on patient mortality (OR=2.5) and survival time (19 vs 367 days). The serum concentration of analyzed interleukins rose significantly with each, additional organ affected by dysfunction (p < 0.001). All analyzed proinflammatory cytokines showed significant predictivity relative to the occurrence of MODS with interleukin 8 serum level prior to ECLS showing the strongest predictive potential for the occurrence of MODS (AUC 0.78). MODS represents a frequent complication in patients undergoing ECLS with a significant impact on survival. Proinflammatory cytokines show prognostic capacity regarding the occurrence and severity of multi-organ dysfunction.

Role of cardiac magnetic resonance imaging in troponinemia syndromes.

Cardiac magnetic resonance imaging (MRI) is an evolving technology, proving to be a highly accurate tool for quantitative assessment. Most recently, it has been increasingly used in the diagnostic and prognostic evaluation of conditions involving an elevation in troponin or troponinemia. Although an elevation in troponin is a nonspecific marker of myocardial tissue damage, it is a frequently ordered investigation leaving many patients without a specific diagnosis. Fortunately, the advent of newer cardiac MRI protocols can provide additional information. In this review, we discuss several conditions associated with an elevation in troponin such as myocardial infarction, myocarditis, Takotsubo cardiomyopathy, coronavirus disease 2019 related cardiac dysfunction and athlete’s heart syndrome.

"Erectile Dysfunction and Metabolic Syndrome. An Entity Little Addressed"

"Erectile Dysfunction and Metabolic Syndrome. An Entity Little Addressed"

SYNDROME OF VEGETATIVE DYSFUNCTION AMONG YOUNG STUDENTS IN VOLGOGRAD EDUCATIONAL INSTITUTIONS

The syndrome of autonomic dysfunction (SVD) is interpreted as a set of polysystemic disorders caused by disorders of the higher autonomic centers. Today, the number of young people who report symptoms of this dysfunction continues to increase. Thus, a significant proportion of students with SVD are at risk of developing abnormalities in their health state, due to dysregulation of vascular tone, aggravated by desynchronosis. The aim of the study studied the incidence of autonomic dysfunction syndrome among students in Volgograd educational institutions. The survey included the study of the state of balance of the autonomic nervous system using the Wayne questionnaire, as well as chronotypes using the Horn-Ostberg test. The results were processed using the methods of mathematical statistics. Installed, it was found that the highest prevalence of vegetative-vascular dystonia (VVD) is among the student youth of the Volgograd region. Among female representatives, VVD is found somewhat more often than among men. Representatives of the owners of arrhythmic and weak evening chronotypes are more susceptible to the development of autonomic dysfunctions. Systematic muscular activity is a limiting factor in the progression of the syndrome of vegetative-vascular dysfunctions. In order to preserve and improve the level of health of students actually is systematic observance of the motor activity, as well as the development of complex programs of physical education, taking into account individual daily biorhythms. Specified recommendations have a preventive focus in regard to the syndrome of autonomic dysfunction and its transformation into the pathology of a particular body system.

Mild Phenotype of Arthrogryposis, Renal Dysfunction, and Cholestasis Syndrome 1 Caused by a Novel VPS33B Variant.

The arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is an autosomal recessive multisystem disease caused by variants in VPS33B or VIPAS39. The classical presentation includes congenital joint contractures, renal tubular dysfunction, cholestasis, and early death. Additional features include ichthyosis, central nervous system malformations, platelet dysfunction, and severe failure to thrive. We studied three patients with cholestasis, increased aminotransferases, normal gamma-glutamyl transferase, and developmental and language delay. Whole exome sequencing analysis identified VPS33B variants in all patients: patients 1 and 2 presented a novel homozygous variant at position c.1148T>A. p.(Ile383Asn), and patient 3 was compound heterozygous for the same c.1148T>A. variant, in addition to the c.940-2A>G. variant. ARCS is compatible with the symptomatology presented by the studied patients. However, most patients that have been described in the literature with ARCS had severe failure to thrive and died in the first 6 months of life. The three patients studied here have a mild ARCS phenotype with prolonged survival. Consequently, we believe that the molecular analysis of the VPS33B and VIPAS39 should be considered in patients with normal gamma-glutamyl transferase cholestasis.

Novel gene mutations in three Japanese patients with ARC syndrome associated mild phenotypes: a case series

BackgroundArthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is a rare autosomal recessive disorder caused by mutations in VPS33B (ARCS1) and VIPAS39 (ARCS2). As per literature, most patients with ARCS died of persistent infections and bleeding by the age of 1 year. We report the first Japanese cases with ARCS1 and ARCS2 who presented with mild phenotypes and were diagnosed via genetic testing.Case presentationCase 1: A 6-year-old boy born to nonconsanguineous Japanese parents presented with jaundice and normal serum gamma-glutamyl transferase (GGT) levels, proteinuria, bilateral nerve deafness, motor delay, failure to thrive, and persistent pruritus. After cochlear implantation for deafness at the age of 2 years, despite a normal platelet count and prothrombin time-international normalized ratio, the patient presented with persistent bleeding that required hematoma removal. Although he did not show any obvious signs of arthrogryposis, he was suspected to have ARCS based on other symptoms. Compound heterozygous mutations in VPS33B were identified using targeted next-generation sequencing (NGS), which resulted in no protein expression. Case 2: A 7-month-old boy, the younger brother of case 1, presented with bilateral deafness, renal tubular dysfunction, failure to thrive, and mild cholestasis. He had the same mutations that were identified in his brother’s VPS33B. Case 3: A 24-year-old man born to nonconsanguineous Japanese parents was suspected to have progressive familial intrahepatic cholestasis 1 (PFIC1) in his childhood on the basis of low GGT cholestasis, renal tubular dysfunction, sensory deafness, mental retardation, and persistent itching. A liver biopsy performed at the age of 16 years showed findings that were consistent with PFIC1. He developed anemia owing to intraperitoneal hemorrhage from a peripheral intrahepatic artery the day after the biopsy, and transcatheter arterial embolization was required. ARCS2 was diagnosed using targeted NGS, which identified novel compound heterozygous mutations in VIPAS39.ConclusionsThe first Japanese cases of ARCS1 and ARCS2 diagnosed using genetic tests were reported in this study. These cases are milder than those previously reported. For patients with ARCS, invasive procedures should be performed with meticulous care to prevent bleeding.

Дети первого года жизни после искусственной вентиляции легких при рождении. Новые подходы к реабилитации

Objective. To improve rehabilitation of infants who received respiratory support at birth. Patients and methods. This prospective comparative study was conducted in the Children's City Polyclinic No 13 of Yekaterinburg and included 131 infants who received different types of artificial lung ventilation (ALV) for some respiratory disorders. All patients were followed up by a pediatrician, neurologist, pulmonologist, and an infectious disease specialist; all of them received appropriate therapy. The experimental group comprised 99 infants who additionally received a course of osteopathic (manual) correction for 8–10 weeks, whereas the control group included 32 infants who received standard therapy only. Patients in the experimental and control groups were matched for all parameters. In addition to chest X-ray, all study participants underwent an assessment of their neurological, somatic, and biomechanical statuses. Osteopathic treatment (4 to 6 sessions lasting 30–40 minutes each) was performed by one osteopathic doctor. Statistical analysis was conducted using the SPSS Statistics.26 software; we calculated Pearson's linear correlation coefficient and used Fisher's exact test and McNemar's test. Differences were considered significant at p &lt; 0.05. Results. Seventy-nine infants (79.8%) initially had both neurological and somatic disorders. Ten patients (10.1%) had either somatic disorders (such as labored nasal breathing, regurgitation, constipation, thermoregulation disorder) or neurological disorders (weather sensitivity, sleep disorders, delayed motor and/or neuropsychiatric development, impaired blood and cerebrospinal fluid dynamics) alone. We identified three groups of major somatic dysfunctions (SDs) in the biomechanical status: local (levels: С0–СI, sternum, thoracoabdominal diaphragm, sacrum); regional (cervical spine–level СII–СVI, laryngopharyngeal complex, lungs, abdominal cavity, skull); and global dysfunction of the dura mater. After treatment, the frequency of all neurological and somatic disorders, as well as the frequency of all SDs reduced in the experimental group (p &lt; 0.001). Pathological changes on chest X-rays (elevated diaphragm, low mobility of the thoracic diaphragm, bullae, pleurodiaphragm atic adhesions, etc.) were detected in 89 patients (67.9%), including 66 infants from the experimental group (66.7%) and 23 infants from the control group (71.8%). Osteopathic (manual) treatment significantly reduced the number of patients with abdominal diaphragm dysfunction (56.6% vs. 26.3%), bullae (35.3% vs. 11.1%), and middle lobe syndrome (8.1% vs. 2%) (p &lt; 0.001). The number of patients with thoracoabdominal diaphragm dysfunction in the control group did not change (n = 18; 56.2%). Positive radiological dynamics was observed in 90.9% of patients from the experimental group and 43.5% of patients from the control group. Moreover, only infants from the control group demonstrated negative radiological dynamics (17.4%). Conclusion. Newborns (both preterm and full-term) with different respiratory disorders who had received all types of ALV were found to have a typical spectrum of SDs. The key aspect of their pathogenesis is primary lesions to the phrenic nerve. Correction of SDs using osteopathic manipulations significantly increased the efficacy of comprehensive treatment, which is confirmed by the results of X-ray examination. Key words: somatic dysfunctions, thoracic diaphragm, phrenic nerve, artificial ventilation, manual therapy, preterm newborns, newborns, osteopathic correction

Severe hemophagocytic syndrome after intravesical BCG instillation with a fatal outcome

Introduction. Hemophagocytic syndrome (HS) after Bacillus Calmette-Guerin (BCG) immunotherapy is extremely rare in everyday practice. Only three times HS have been reported on in the world until now. BCG is used for preventing the recurrence of superficial tumors of the urinary bladder. The first extensive research was conducted by Morales, since when his treatment protocol has been in use. Severe complications are rarely seen. Case report. A 55 year-old patient in bad condition was transferred to Clinic for urology after second round of BCG immunotherapy (Morales protocol) after transurethral electroresection of bladder tumor (TURBT). Computed tomography (CT) of the abdomen and lesser pelvis was performed, which didn?t indicate any clear signs of organ failure or disease. Hemophagocytic syndrome (HS) after BCG immunotherapy was suspected. During further hospitalization, the patien?s already severe condition further deteorited and became more complicated, in the form of the multiorgan disfunction syndrome (MODS). Death occurred on the sixth day of hospitalization. Conclusion. Secondary HS after BCG immunotherapy is an extremely rare disease that is accompanied by a severe general condition of the patient, with many life-threatening complications that can lead to death. We have presented a case of severe HS after BCG immunotherapy that caused death of the patient. This case was unique because, for the first time, the possible causative agent was isolated-Mycobacteria.

Profile and role of immune function changes of T lymphocytes in patients with acute pancreatitis

In recent decades, with the development of the pathogenesis of Acute severe pancreatitis (SAP) and the improvement of clinical treatment techniques, the mortality rate of SAP is still over 10% . Recent studies have shown that immune dysregulation plays an important role in the pathogenesis of AP, especially in SAP. A meta-study points to widespread concern for the discovery of immunosuppression by networked cytokines in the course of AP. In the early stages of AP, high cytokine levels play a leading role in the development of SIRS pathological conditions, which result in a cascade of inflammatory cytokines that induce the release of immunocompetent cells, leading to an excessive immune response. In the later stages of Compensatory anti-inflammatory response syndrome (CARS), the body over-releases anti-inflammatory agents and has an immunosuppressive process, but contributes to the development of the risk of secondary infection and increases the likelihood of Multiple organ disfunction syndrome (MODS). The study was aimed to measure T-lymphocyte immune function changes of patients with acute pancreatitis and to explore BISAP scoring system in clinical applications.

Myocarditis and diaphragmatic rhabdomyolysis with respiratory failure in a patient with metastatic melanoma treated with Nivolumab

Immunotherapy dramatically changed history of melanoma patients with a clinical benefit never seen before. Nevertheless, severe and unexpected adverse effects can occur, fortunately rarely. We reported the case of a 75-year-old male patient affected by metastatic melanoma who developed myocarditis and acute rhabdomyolysis with secondary diaphragmatic dysfunction and consequent pulmonary restrictive syndrome after Nivolumab monotherapy. Blood tests and ultrasonography of the diaphragm revealing left hypokinesis suggested a Nivolumab-related rhabdomyolysis, as an immune-mediated adverse event. The rhabdomylolysis involved the diaphragm with consequent diaphragmatic weakness and respiratory distress. The patient had a slow but slight and progressive improvement of symptoms and vital signs post-treatment with high-dose corticosteroids. With this case report, we want to highlight the importance of rapid recognition and treatment of rare and unexpected, but potential serious immune-related adverse events. These events might happen despite the remarkable clinical benefits of immune checkpoint inhibitors. We do not know which patients will benefit from these therapies and why, when and in which cases adverse event will occur: we must not lower our attention.

Acute accidental inhalation of Chlorine gas: A mini review

The Authors report an accidental gas exposure of Chlorine gas in a worker. This accident is very uncommon and can lead to important life-threatening conditions, such as Reactive Airway Disfunction Syndrome (RADS) and Acute Respiratory Distress Syndrome (ARDS) with important pulmonary disfunctions and even death. This syndrome results are reversible when a quick and appropriate intensive treatment is performed.

Citicoline in the Treatment of Mild Cognitive Impairment in Blood Relatives of Patients with Alzheimer’s Disease: Immediate and Long-Term Effects of Course Therapy

The aim was to study immediate and long-term (post-therapeutic) effects of a three-month course of therapy with citicoline in 1st-degree relatives of patients with Alzheimer’s disease (AD). All the included relatives of patients with AD revealed signs of minimal cognitive dysfunction (MCD) and mild cognitive decline syndrome (MCI — Mild Cognitive Impairment, ICD-10 code F06.7). Study participants: the study involved 90 first-degree relatives: 24 with MCI and 66 with MCD. Study design: an open-label comparative multidisciplinary study of the six-month dynamics of cognitive functioning of two groups of relatives who received a three-month course of citicoline therapy. The baseline indicators of the cognitive functioning of relatives with MCI syndrome and MKD were compared with the indicators at the end of the three-month course of therapy with citicoline at a daily dose of 1000 mg as well as 3 months after the end of the course of treatment. Methods: clinical, psychopathological, neuropsychological, psychometric, genetic, statistical ones. Results: а significant positive effect of the course therapy with citicoline on the cognitive impairment of 1st degree AD-patients’ relatives with minimal cognitive dysfunction and more pronounced cognitive impairments met the diagnostic criteria for MCI syndrome has been found. A significantly greater value of both immediate and long-term therapeutic effect of MKD compared with MCI in relatives was established by psychometric and neuropsychological indicators characterizing voluntary memorization of verbal and visual stimuli, optical and spatial activity, voluntary attention, and associative verbal thinking. Conclusion: the results of the study can be used as the basis for a model of prevention of the progression of cognitive deficit and the development of dementia in persons with a high risk of developing AD, i.e. in individuals with both genetic risk and signs of cognitive impairment.

Вплив ендотоксикозу на вегетативний статус пацієнтів з хронічним панкреатитом

Актуальність. Одними з визначальних типових клініко-патогенетичних синдромів формування і тяжкості перебігу хронічного панкреатиту (ХП) є синдроми ендогенної інтоксикації (СЕІ) та вегетативної дисфункції (ВД). Досліджень гематологічних індексів запалення та інтоксикації, а особливо у співставленні із параметрами вегетативного статусу при ХП нами знайдено не було, що й мотивувало до проведення даної науково-дослідної роботи. Мета дослідження: встановити взаємозв’язки гематологічних індексів запалення та інтоксикації і параметрів вегетативного статусу пацієнтів із хронічним панкреатитом. Матеріали та методи. Було обстежено 69 пацієнтів з діагнозом ХП, які лікувалися амбулаторно. Визначали наступні гематологічні індекси: лейкоцитарний індекс інтоксикації (ЛІІ), індекс адаптації (ІА) з подальшим визначенням типу неспецифічної адаптаційної реакції, лімфоцитарно-гранулоцитарний індекс (ІЛГ). Вивчались кореляційні зв’язки ЛІІ з параметрами психо-емоційного стану (нейротизмом, реактивною (РТ) та особистісною (ОТ) тривожністю згідно з опитувальниками Айзенка, Спілбергера-Ханіна), ВД за даними опитувальника Вейна, тривалістю захворювання. Результати. У 63% пацієнтів з хронічним панкреатитом встановлено наявність ендогенної інтоксикації легкого та середнього ступеня тяжкості за індексом Кальфа-Каліфа, що робить необхідним застосування препаратів, спрямованих на її корекцію. Встановлено достовірні кореляційні зв’язки між ЛІІ та особистісною тривожністю (прямий слабкий r=0,23, p&lt;0,05), нейротизмом (прямий середньої сили r=0,41, p&lt;0,05), вегетативною дисфункцією (прямий слабкий r=0,1, p&lt;0,05), тривалістю захворювання (прямий слабкий r=0,15, p&lt;0,05), структурним станом підшлункової залози за УЗД-проявами у балах (прямий слабкий r=0,29, p&lt;0,05), рівнем α-амілази панкреатичної (прямий середньої сили r=0,30, p&lt;0,05). Отримані результати довели наявність достовірних взаємовпливів параметрів запалення та ендотоксикозу з показниками вегетативного статусу і стану підшлункової залози. Це робить необхідним призначення хворим з ХП протизапальних і вегетотропних засобів для посилення протокольного лікування. Висновки. Серед пацієнтів з ХП сприятливі адаптаційні реакції спостерігались лише у 36% обстежених, несприятливі – у 25%, проміжні – у 39%, а середнє значення індекса адаптації становило – 0,48±0,18, що відповідає верхній межі реакції орієнтування. Це мотивує до додаткового призначення таким пацієнтам з ХП вегетотропних і адаптогенних препаратів. Лише у 10% пацієнтів з хронічним панкреатитом загальна імунна відповідь не має відхилень від адекватної імунної реакції, у 48% обстежених спостерігається нездатність імунної системи завершити запалення, у 42% – переважання аутоімунного компоненту інтоксикації, що потребує посилити протизапальну терапію біорегуляційними препаратами з метою гармонійного завершення запалення.