Lack of Difference in Tocilizumab Efficacy in the Treatment of Severe COVID-19 Caused by Different SARS-CoV-2 Variants.

Tocilizumab (TOC) is presumed to be an effective and safe treatment for severe COVID-19, but its usefulness has not been yet investigated for different SARS-CoV-2 variants. This study aimed to evaluate the influence of TOC on mortality in patients with severe COVID-19 caused by Delta and non-Delta SARS-CoV-2 variants. In a retrospective analysis, we compared the medical records of 78 and 224 patients with severe COVID-19 due to Delta and non-Delta variants, respectively. A total of 30 patients with Delta and 84 with non-Delta variants were treated with TOC in addition to standard therapy. There were no statistically significant differences in mortality rate when comparing Delta vs. non-Delta patients nor when comparing those treated with TOC vs. not treated with TOC in both variants. Using a logistic regression model, in the examined population as a whole, we found an increased (p < 0.05) risk of death as leukocyte and erythrocyte counts decreased and as procalcitonin increased. Increased procalcitonin was significant for mortality in the Delta group, while decreased IL-6, leukocytes, and platelets and increased fibrinogen and procalcitonin were significant in the non-Delta group. Tocilizumab efficacy in severe COVID-19 does not differ between Delta or non-Delta virus variants. The Delta variant of SARS-CoV-2 does not increase mortality when compared to other virus strains.

Effectiveness of emergency obstetric care training at the regional level in Ukraine: a non-randomized controlled trial.

BACKGROUND: Emergency obstetric care training, using Advances in Labour and Risk Management (ALARM) International Program (AIP) was implemented in Ukraine, a country with universal access to skilled perinatal and obstetric care but restricted resources. A total of 577 providers (65.5% of total) from 28 maternal clinics attended a 5-day training session focused on the five main causes of maternal mortality, with hands-on skill workshops, pre- and post- tests, and an objective structured clinical examination. The effects of this emergency obstetric care training on maternal outcomes is the subject of this paper. METHODS: A non-randomized controlled trial was conducted. The pilot areas where the training was implemented consisted of 64 maternity clinics of which 28 were considered as cases and 36 non-participating clinics were the referents. Data on maternal outcomes were collected for a 2-year span (2004-2005) prior to the trainings, which took place 2006-2007 and again after implementation of the trainings, from 2008 to 2009. Information was collected from 189,852 deliveries. Outcomes for the study were incidences of operative delivery and postpartum hemorrhage. Non-parametric statistics, meta-analyses, and difference in difference (DID) estimation were used to assess the effect of the AIP on maternal indices. RESULTS: DID analysis showed that after the training, compared to the referents, the cases had significant reduction of blood transfusions (OR: 0.56; 95%CI: 0.48-0.65), plasma transfusions (OR: 0.70; 95%CI: 0.63-0.78), and uterus explorations (OR: 0.64; 95%CI: 0.59-0.69). We observed a non-significant reduction of postpartum hemorrhage ≥1000 ml (OR: 0.92; 95%CI: 0.81-1.04; P = 0.103). Utilization of vacuum extraction for vaginal delivery increased (OR: 2.86; 95%CI: 1.80-4.57), as well as forceps assisted delivery (OR: 1.80; 95%CI: 1.00-3.25) and cesarean section (OR: 1.11; 95%CI: 1.06-1.17). There was no change in the occurrence of postpartum hysterectomy and maternal mortality. CONCLUSIONS: After one week of Emergency Obstetrics Care training of the obstetric staff in a setting with universal access to perinatal and obstetric care but restricted resources, an association with the reduction of postpartum hemorrhage related interventions was observed. The effects on the use of vacuum extraction and cesarean section were minimal. TRIAL REGISTRATION: Retrospectively registered 071212007807 from 07/12/2012.

FEMOROPOPLITEAL ANGIOPLASTY VS OPEN SURGERY FOR CHRONIC LIMB-THREATENING ISCHEMIA.

OBJECTIVE: The aim: To compare the results of femoro-popliteal PTA vs open surgery in chronic limb-threatening ischemia (CLTI) and analyze clinical efficacy long-term results. PATIENTS AND METHODS: Materials and methods: Between 2018 - 2019, 145 patients with CLTI who underwent femoro-popliteal arterial segment steno-occlusive lesions (SOL) unilateral revascu¬larization. Open surgery were performed for - 48 (33, 1℅), percutaneous transluminal angioplasty (PTA) for - 73 (50.3%), and were treated with hybrid surgical interventions for - 24 (16.6%). RESULTS: Results: During the analysis, no statistically significant difference was found among the three groups patients indicators. According to the diabetes patients indicator, the differences among the groups are statistically significant (p<0.001), diabetes was present in only 16.7% of open surgical intervention group patients, 45.8% of PTA group patients, 54.8% of the hybrid surgery group patients. In the overall comparison 2-year limb preservation after open surgery 93.8%, after PTA 91.7%, and after hybrid surgery 91.6%; amputations: open surgery - 6.2% PTA- 8.2 %, hybrid surgery -8.3%; exemption from surgical re-intervention: open surgery - 68.7%, PTA- 58.9%, hybrid surgery - 75%. There were no differences in limb preservation and amputation between open surgery, hybrid intervention, and PTA. A difference was found only in reintervention tactic among the open surgery and PTA groups as opposed to the hybrid surgery. CONCLUSION: Сonclusions: Limb salvage and CLTI patients survival after open surgery and PTA who were not performed major amputation in 2 years term after revascularization were comparable regardless of treatment method.

Prediction of mortality in severely injured patients with facial bone fractures.

PURPOSE: Identify the most common concomitant injuries associated with facial trauma, and compare the efficacy of various scoring systems in estimation of mortality risks in this category of patients. METHODS: The study evaluated patients with facial and concomitant injuries, who received the multidisciplinary treatment in a specialized trauma hospital. Values of New Injury Severity Score, Glasgow Coma Scale, Facial Injury Severity Scale, age, and length of hospital stay were statistically analysed to determine presence of relationships between these indicators and define factors that significantly associated with lethal outcome. RESULTS: During 6-year observation period, 719 patients were treated with multiple or combined maxillofacial trauma, brain injuries and polytrauma. Mainly with isolated midface bones (49.7%), pan-facial (34.6%), mandible (12.9%), and frontal bone and walls (2.8%) fractures. Mortality was (2.2%). The mortality rates in patients with severe pan-facial fractures were higher (p = 0.008) than in single anatomical area (6% vs 1.5%). Age, GCS, and NISS were the most reliable indicator of lethal outcome. CONCLUSION: Age, Glasgow Coma Scale and New Injury Severity Score main factors, that predicts lethal outcome with high accuracy. New Injury Severity Score value ≥ 41 is a critical level for survival prognosis and should be considered in treatment planning and management of this category of patients.

Comparison of the Effect of Unfractionated Heparin and Enoxaparin Sodium at Different Doses on the Course of COVID-19-Associated Coagulopathy.

BACKGROUND: COVID-19-associated coagulopathy (CAC) exacerbates the course of coronavirus infection and contributes to increased mortality. Current recommendations for CAC treatment include the use of low-molecular weight heparins (LMWH) at prophylactic or therapeutic doses, as well as the use of unfractionated heparin (UFH). METHODS: A randomised, controlled trial enrolled 126 patients hospitalised in the intensive care unit with severe COVID-19 complicated by CAC. The effects of LMWH at preventive and therapeutic doses and UFH at therapeutic doses on mortality and intubation rates were compared. RESULTS: The number of intubations and deaths showed no significant difference depending on the anticoagulant therapy used. However, multivariate logistic regression models revealed an increased risk of intubation (p = 0.026, odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.15-9.59), and an increased risk of death (p = 0.046, OR = 3.01, 95% CI 1.02-8.90), for patients treated with LMWH at a prophylactic dose but not at a therapeutic dose as compared to patients treated with UFH when controlling for other risk factors. CONCLUSIONS: The use of unfractionated heparin in the treatment of COVID-19-associated coagulopathy seems to be more effective at reducing the risk of intubation and death than enoxaparin at prophylactic doses.

Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome.

BACKGROUND: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. METHODS: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In the MAS and CRS groups, treatment results were assessed depending on whether or not tocilizumab was used. RESULTS: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/mL, p < 0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p = 0.043), RR = 2.1 (95% CI 1.0-4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p = 0.013), RR = 0.50 (95% CI 0.25-0.99). CONCLUSIONS: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients, it contributed to reduced mortality.

Prognostic model of skin cancer risk assessment.

OBJECTIVE: Introduction: Early detection of people at risk of skin cancer will reduce the incidence of disease, lower the cost of health technologies and decrease anxiety level in patients. The aim of the work is to create a prognostic model for identifying people at increased risk of skin cancer development. PATIENTS AND METHODS: Material and methods: We used the results of our previous research on identifying risk factors in patients with actinic keratosis (AK), squamous cell carcinoma in situ (SCCis) and cutaneous squamous cell carcinoma (cSCC), who were under dynamic observation at the State Institution of Science "Research and Practical Centre of Preventive and Clinical Medicine" State Administrative Department (hereinafter SIS) in 2014-2017. RESULTS: Results: The prognostic model is valid, AUC = 0.97 (95% CI 0.96 - 0.99) showing a significant association of the risk of skin cancer development with the following factors: patient's age, sunburns, using skin sunscreens, exposure to the sun in recent times, exposure to radiological materials, drug administration (antiarrhythmic drugs, antihypertensive medications, hormonal contraceptives, antibiotics), burdened family history (melanoma, squamous cell cancer). Model sensitivity was 95.1% (95% CI 91.6% - 97.4%), specificity - 88.5% (95% CI 84.6% - 91.8%). CONCLUSION: Conclusions: The developed and analysed mathematical risk prediction system made it possible to identify 11 factors which are significantly associated with risk of skin cancer development. The prognostic model might be offered for specialists in taking decision at the stage of primary and secondary prevention of skin cancer.

Non-genetic risk factors for early and late age at menarche in Eastern Ukrainian females.

ABSTRACT: BACKGROUND: Age at menarche is a reproductive trait, which is largely influenced by environmental factors. Each population has a set of lifestyle factors that may shift age at menarche in different direction. Populations of Eastern Slavs, particularly Ukrainians, are underrepresented in studies of reproductive health. The objective of the present research was to determine important non-genetic risk factors, which may contribute to menarcheal onset in Eastern Ukrainians. METHODS: In total 620 females aged 17-25 years participated in the cross-sectional survey. The questionnaire included lifestyle factors previously reported in other populations as those, which might affect age at menarche. The risk factors for early and late age at menarche were determined using logistic regression models. The models were validated by receiver operating curves. RESULTS: Body composition in the prepubertal stage as presented by responders seems to have the strongest association with age at menarche. Those who were shorter and thinner as compared to their peers at age six had significantly more chance to start menstruating later (OR = 1.66, 95% CI [1.01-2.73]) and reduced chance to have menarche before 12 years old (OR = 0.32, 95% CI [0.14-0.73]). Maternal smoking during pregnancy and low protein intake reported during childhood may decrease a probability of late age at menarche. CONCLUSIONS: Although overall body composition at age of six was a main trait, which was associated with menarcheal timing, more information on body measurements (e.g. waist-hip ratio) in prepubertal stage would help to establish a greater degree of accuracy on this matter.

Neck circumference as a risk factor of screen-detected diabetes mellitus: community-based study.

BACKGROUND: Whereas an increase of neck circumference (NC) had been recently identified as a new independent cardiovascular disease (CVD) and metabolic syndrome risk factor, similar assessments concerning screen-detected diabetes mellitus (SDDM) have not been made. Thyroid gland volume (ThV) can potentially affect NC however the significance of this influence concerning the risk of NC-related disease is unknown. METHODS: We performed a ThV-adjusted evaluation of NC within a population-based investigation of SDDM and impaired glucose regulation (IGR) prevalence. This study contains fasting plasma glucose (FPG) and 75 g 2-h glucose tolerance test results (2-hPG) of 196 residents of Kyiv region, Ukraine, randomly selected from the rural population older than 44 y.o. who were not registered as diabetes mellitus patients. Standard anthropometric (height; weight; blood pressure; waist, hip circumferences), NC and ultrasonography ThV measurements were performed, hypotensive medication, CVD events and early life nutrition history considered. HbA1c was measured, if FPG/2-hPG reached 7.0/11.1 mmol/l respectively; HbA1c level 6.5 % was considered to be SDDM diagnostic; IGR if FPG/2-hPG reached 6.1/7.8 but less than 7.0/11.1 mmol/l respectively. RESULTS: Neck circumference among women with normal FPG/2-hPG was 35 (33-36) cm, IGR 36 (34.5-38) cm, SDDM HbA1c < 6.5 % 42 (40-43) cm, HbA1c > 6.5 % 42.5 (40-44) cm, p < 0.001, and for men from the same groups 38.5 (36.5-41.5) cm; 39 (37-42) cm; 42 (40-43) cm; 42.5 (40-44) cm, p = 0.063; medians (QI-QIII). Gender-adjusted logistic regression OR for SDDM HbA1c > 6.5 % vs. normal FPG/2-hPG category depending of NC as a continued variable, equaled to 1.60 (95 % CI 1.27-2.02) per cm. Additional adjusting by ThV, body mass or waist/hip index, high blood pressure, acute CVD events, or starvation history did not significantly influence this risk. CONCLUSION: Neck circumference is a new risk factor of SDDM that is independent from other indicators of adipose tissue distribution as well as from the ThV.