Early Use of Erenumab vs Nonspecific Oral Migraine Preventives: The APPRAISE Randomized Clinical Trial.

Importance: Patients with migraine often cycle through multiple nonspecific preventive medications due to poor tolerability and/or inadequate efficacy leading to low adherence and increased disease burden. Objective: To compare the efficacy, tolerability, patient adherence, and patient satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments. Design, Setting, and Participants: The 12-month prospective, interventional, global, multicenter, active-controlled, randomized clinical trial comparing sustained benefit of 2 treatment paradigms (erenumab qm vs oral prophylactics) in adult episodic migraine patients (APPRAISE) trial was a 12-month open-label, multicenter, active-controlled, phase 4 randomized clinical trial conducted from May 15, 2019, to October 1, 2021. This pragmatic trial was conducted at 84 centers across 17 countries. Overall, participants 18 years or older with a 12-month or longer history of migraine, and 4 or more but fewer than 15 monthly migraine days (MMDs) were included. Interventions: Patients were randomized (2:1) to receive erenumab or OMPMs. Dose adjustment was permitted (label dependent). Main Outcomes and Measures: The primary end point was the proportion of patients completing 1 year of the initially assigned treatment and achieving a reduction of 50% or greater from baseline in MMDs at month 12. Secondary end points included the cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders according to the Patients' Global Impression of Change (PGIC) scale at month 12 for patients taking the initially assigned treatment. Results: A total of 866 patients were screened, of whom 245 failed the screening and 621 completed the screening and baseline period. Of the 621 randomized patients (mean [SD] age, 41.3 [11.2] years; 545 female [87.8%]; 413 [66.5%] in the erenumab group; 208 [33.5%] in the OMPM group), 523 (84.2%) completed the treatment phase, and 98 (15.8%) discontinued the study. At month 12, significantly more patients assigned to erenumab vs OMPM achieved the primary end point (232 of 413 [56.2%] vs 35 of 208 [16.8%]; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P <.001). Compared with OMPMs, treatment with erenumab showed higher responder rate (314 of 413 [76.0%] vs 39 of 208 [18.8%]; OR, 13.75; 95% CI, 9.08-20.83; P <.001) on the PGIC scale (≥5 at month 12). Significant reduction in cumulative average MMDs was reported with erenumab treatment vs OMPM treatment (-4.32 vs -2.65; treatment difference [SE]: -1.67 [0.35] days; P < .001). Substantially fewer patients in the erenumab arm compared with the OMPM arm switched medication (9 of 413 [2.2%] vs 72 of 208 [34.6%]) and discontinued treatment due to adverse events (12 of 408 [2.9%] vs 48 of 206 [23.3%]). No new safety signals were identified. Conclusions and Relevance: Results of this randomized clinical trial demonstrated that earlier use of erenumab in patients with EM who failed 1 or 2 previous preventive treatments provided greater and sustained efficacy, safety, and adherence than continuous OMPM. Trial Registration: ClinicalTrials.gov Identifier: NCT03927144.

Sense of happiness in Polish patients with multiple sclerosis.

INTRODUCTION: Happiness is crucial to patient well-being and their acceptance of their disease. The aim of this study was to assess the sense of happiness in persons with multiple sclerosis (PwMS), compare it to the level of happiness in patients with other neurological conditions, and determine which factors affect the sense of happiness in PwMS. MATERIAL AND METHODS: Five hundred and eighty-nine PwMS and 145 control subjects (post-stroke patients with chronic pain syndromes and neuropathies) were included in the study. Due to the differences between the groups in terms of demographic variables, an adjusted group of PwMS (n = 145) was selected from the entire group of PwMS. All patients were assessed using the Oxford Happiness Questionnaire (OHQ), the Satisfaction with Life Scale (SLS), and the Family APGAR Questionnaire. Based on regression analysis, the study examined which variables affected the level of happiness in the groups. RESULTS: Analysis of the OHQ scores showed that PwMS had a lower sense of happiness compared to the control group in the overall score [113.21 (25-42) vs. 119.88 (25-49), respectively; p = 0.031] and the subscales (OHQ subscale 1 - 54.52 vs. 57.84, respectively; p = 0.027; subscale 2 - 35.61 vs. 37.67; respectively; p = 0.044). Based on linear regression analysis, life satisfaction (ß = 0.40; p < 0.001), positive orientation (ß = 0.32; p < 0.001), and primary education (ß = 0.08; p = 0.009) were the most significant predictors of a higher level of happiness in PwMS. Similar results were found in the control group. CONCLUSIONS: The sense of happiness in PwMS was lower than in patients with other conditions. The most important factors influencing happiness included life satisfaction and positive orientation. Influencing these predictors should be the aim of psychological interventions, especially in patients with a reduced sense of happiness.

Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multi-centre, retrospective, cohort study during the COVID-19 pandemic.

INTRODUCTION: Treatment with cladribine tablets is indicated in highly active relapsing-remitting multiple sclerosis (RRMS). Cladribine tablets proved safe and effective in the pivotal CLARITY trial, but that trial included primarily treatment-naïve patients. In clinical practice however, cladribine tablets are often given to patients who have failed other treatments. Therefore, this study investigated the real-world safety and efficacy of cladribine tablets. MATERIAL AND METHODS: We gathered data from nine MS clinical centres across Poland for patients with RRMS who started treatment with cladribine tablets from December 2019 to June 2022. RESULTS: We enrolled 140 patients, with follow-up data available for 136 in year 1 and for 66 in year 2. At baseline, the mean age was 35.6 years, mean disease duration was 7.3 years, median EDSS score was 2.5, and 94% of patients were treatment- -experienced. Thirty-nine patients (27.9%) had undergone COVID-19, and 94 (67.1%) were vaccinated against COVID-19. The annualised relapse rate (ARR) decreased from 1.49 at baseline to 0.33 in year 1 (p < 0.001) and to 0.25 in year 2 (p < 0.001). The percentage of relapse-free patients increased from 11.5% at baseline to 70.2% in year 1 and 82.1% in year 2. The percentage of patients with active lesions decreased from 91.4% at baseline to 36.2% in year 1 and 18.2% in year 2. EDSS score remained stable or improved in 83.7% of patients in year 1 and 89.6% in year 2. No evidence of disease activity (NEDA-3) was achieved in 42.7% of patients in year 1 and 66.7% in year 2. Only one patient (0.72%) had grade 4 lymphopenia and 21 (15.1%) had grade 3 lymphopenia. Varicella zoster virus infections occurred in three patients. Eight patients discontinued treatment with cladribine: five due to inefficacy, one due to lymphopenia, and two due to a personal decision. CONCLUSIONS: Cladribine tablets proved safe and effective in a real-world cohort of treatment-experienced patients. However, the efficacy measures improved to a lesser extent in our cohort than in the pivotal clinical trial, which is probably due to a higher proportion of treatment-experienced patients in our cohort.

Efficacy of Pregabalin and Duloxetine in Patients with Painful Diabetic Peripheral Neuropathy (PDPN): A Multi-Centre Phase IV Clinical Trial-BLOSSOM.

INTRODUCTION: Our trial (ClinicalTrials.gov Identifier: NCT04246619) evaluates the efficacy of two generic medications, pregabalin and duloxetine, for treating pain in PDPN patients. METHODS: The patients were randomised either into the pregabalin (99) or the duloxetine (102) arm. Pain was evaluated using the DN-4 questionnaire, and visual analogue scales (VASs, 0-100 mm) were used to measure the average pain intensity (API), worst pain intensity (WPI) in the last 24 h and current pain intensity (CPI). RESULTS: The proportion of patients with a clinically significant improvement in the API at Week 12 was 88.3% [CI 81.7%, 94.8%] in the pregabalin arm and 86.9% [CI 76.7%, 97.1%] in the duloxetine arm. After 12 weeks, the CPI, API, and WPI decreased by -35.3 [-40.5, -30.0], -37.0 [-41.4, -32.6], and -41.6 [-46.6, -36.5] in the pregabalin arm, and by -35.0 [-39.2, -30.7], -36.9 [-41.5, -32.3], and -40.0 [-44.8, -35.2] in the duloxetine arm (all in mm, all p < 0.001). CONCLUSION: Our results demonstrate that pregabalin and duloxetine are effective medications for treating pain in PDPN in more than 86% of all randomised patients.

Case report: Flail leg syndrome in familial amyotrophic lateral sclerosis with L144S SOD1 mutation.

We observed a Polish family with familial amyotrophic lateral sclerosis with heterozygous L144S SOD1 mutation, which manifested clinically as flail leg syndrome. Flail leg syndrome is a rare phenotype of amyotrophic lateral sclerosis, with slow progression, long survival, and predominance of lower motor neuron signs at onset, as a triad of distal paresis, muscle atrophy, and hyporeflexia/areflexia, confined to the lower limbs for an extended period of time. Although familial amyotrophic lateral sclerosis is usually associated with a worse prognosis than the sporadic form of the disease, the clinical course of the disease in patients with L144S SOD1 mutation is benign, with slow progression and long survival. This unique case report provides an in-depth clinical analysis of all of the symptomatic members of a family, who were diagnosed with amyotrophic lateral sclerosis in our clinic, including three siblings (two brothers and a deceased sister) with flail leg syndrome and their fraternal aunt, who has been previously misdiagnosed with cervical myelopathy and is living with symptoms of the disease for 15 years. Sanger sequencing of the SOD1 gene was performed in all of the living patients, revealing an L144S (c.434T>C, p.Leu145Ser) heterozygous mutation. The aim of this case report is to increase the physician's awareness of the atypical phenotypes of amyotrophic lateral sclerosis and hopefully, to encourage further research on the factors responsible for delayed disease progression in patients with L144S SOD1 mutation.

Comparison of the clinical characteristics, glycemic control, and pregnancy outcomes between women with gestational diabetes mellitus in waves I and III of the COVID-19 pandemic: a reference center report.

OBJECTIVES: The medical care of patients with gestational diabetes mellitus (GDM) during the COVID-19 pandemic was influenced by changing epidemiological conditions and government regulations. Aim - To compare the clinical pregnancy data of GDM women between waves I and III of the pandemic. MATERIAL AND METHODS: We performed a retrospective analysis of medical records from the GDM clinic and compared the periods of March-May 2020 (wave I) and March-May 2021 (wave III). RESULTS: Women with GDM during wave I (n = 119) compared to wave III (n = 116) were older (33.0 ± 4.7 vs 32.1 ± 4.8 years; p = 0.07), booked later (21.8 ± 8.4 vs 20.3 ± 8.5 weeks; p = 0.17), and had their last appointment earlier (35.5 ± 2.0 vs 35.7 ± 3.2 weeks; p < 0.01). Telemedicine consultations were used more frequently during wave I (46.8% vs 24.1%; p < 0.01), while insulin therapy was used less often (64.7% vs 80.2%; p < 0.01). Mean fasting self-measured glucose did not differ (4.8 ± 0.3 vs 4.8 ± 0.3 mmol/L; p = 0.49), but higher postprandial glucose was reported during wave I (6.6 ± 0.9 vs 6.3 ± 0.6 mmol/l; p < 0.01). Pregnancy outcome data were available for 77 wave I pregnancies and 75 wave III pregnancies. The groups were similar in terms of gestational week of delivery (38.3 ± 1.4 vs 38.1 ± 1.6 weeks), cesarean sections (58.4% vs 61.3%), APGAR scores (9.7 ± 1.0 vs 9.7 ± 1.0 pts), and birth weights (3306.6 ± 457.6 g vs 3243.9 ± 496.8 g) (p = NS for all). The mean wave I neonate length was slightly higher (54.3 ± 2.6 cm vs 53.3 ± 2.6 cm; p = 0.04). CONCLUSIONS: We identified differences between wave I and wave III pregnancies for several clinical characteristics. However, nearly all pregnancy outcomes were found to be similar.

Religious meaning system and life satisfaction: the mediating role of meaning in life among Polish people with multiple sclerosis.

Introduction: The complexity of the associations between religiosity and indicators of well-being suggests the presence of a mediating mechanism. Previous studies indicate that religion may influence subjective well-being because it helps to find meaning and purpose. Therefore, the aim of our study was to examine the mediating role of the presence and search dimensions of meaning in life in the relationship between religious meaning system and life satisfaction in patients with multiple sclerosis (MS). Methods: This cross-sectional study included 600 MS patients recruited from Poland who completed the Satisfaction with Life Scale (SWLS), the Religious Meaning System Questionnaire (RMS) and the Meaning in Life Questionnaire (MLQ). Model 6 of Hayes PROCESS was used to test the hypotheses. Results: The results of our research indicate that there was a significant indirect effect of religious meaning system on life satisfaction through the presence of meaning in life. The specific indirect effect of religious meaning system on life satisfaction through searching for meaning in life was not significant. Discussion: The results of our study are relevant because they show that religion as a meaning system is positively related to the presence of meaning in life, which in turn positively predicts life satisfaction. This is particularly important in the case of incurable illness, where finding meaning in life is one of the natural stages of adaptation. By incorporating these findings into mental health practice, professionals can enhance the holistic well-being of people coping with MS and contribute to a more comprehensive and effective approach to mental health care.

Higher scanning frequency is correlated with less fear of hypoglycemia in type 1 diabetes patients using isCGM.

Background: Frequent scanning of intermittently scanned continuous glucose monitoring (isCGM) devices is associated with improvements in glycemic indices. Limited data is available for its correlation with fear of hypoglycemia (FOH), an established factor affecting quality of life and glycemic control in type 1 diabetes (T1DM). Aim: The aim of the study was to analyze the association of sensor scanning frequency with FOH and glycemic indices in T1DM patients using isCGM. Subjects and methods: T1DM patients using isCGM were eligible. Clinical data and Ambulatory Glucose Profile (AGP) reports were obtained from medical records. At outpatient visits, AGP of last 14 days prior to visit were analyzed and FOH was assessed using Hypoglycemia Fear Survey II (HFS II). Results: We included 77 consecutive T1DM patients (58 females, 19 males). Mean age was 34.1 ± 10.2 years and mean T1DM duration was 14.7 ± 12.0 years. Baseline mean glycemic indices were as follows: mean glucose - 155.8 ± 29.8 mg/dL; GMI - 53.3 ± 7.5 mmol/mol; TIR - 66.4 ± 17.8%; TBR70 - 4.5 ± 4.1%; TBR54 - 0.6 ± 1.2%; TAR180 - 29.2 ± 17.9%; TAR250 - 9.6 ± 10.4%; %CV - 36.7 ± 8.3. Average scanning frequency was 13.8 ± 7.8 scans/day. Mean HFS II scores were 16.1 ± 7.2 and 18.7 ± 12.2 in behavior and worry subscale, respectively. Correlation was confirmed between scanning frequency and mean glucose, GMI, TIR, TBR70, TAR180, TAR250, %CV and HFS II total, and HFS II - B (p<0.05 for all statistics). Conclusions: For the first time, we report that higher scanning frequency is associated not only with better glycemic indices but also with less FOH in T1DM adult patients using isCGM.

Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. METHODS: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26-52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose-response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. FINDINGS: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0-4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79-1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93-1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85-1·32]; t statistic -0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91-2·71]). INTERPRETATION: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. FUNDING: Bayer AG.

Effect of the Trunk and Upper Limb Passive Stabilization on Hand Movements and Grip Strength Following Various Types of Strokes-An Observational Cohort Study.

Almost half of the patients surveyed report impaired function of the upper limbx and handx after stroke. The effect of the passive trunk and shoulder stabilization on the recovery of coordinated hand movement is unclear. This study examined whether passive stabilization of the trunk and shoulder could improve the functional state of the hands after various types of strokes. It is an observational prospective cohort study conducted at the Rehabilitation Clinic in two parallel groups of patients with four different types of strokes (hemorrhagic and ischemic of the brain, similar to the cerebellum). A total of 120 patients were analyzed. Patients were examined in various positions: sitting without a backrest with the upper limb adjacent to the body, supine with the upper limb perpendicular to the body, and supine with the arm stabilized in relation to the patient's body. Hand Tutor devices and a hand dynamometer were used for the measurements. The frequency and maximum range of motion as well as the grip strength were measured in three different positions of the trunk and upper limb. Passive stabilization of the trunk and shoulder showed more statistically significant differences in Group II. In group II, both in patients after hemorrhagic stroke (wrist Hz p = 0.019; wrist ROM p = 0.005; Hz F5 p = 0.021; Hz F4 p = 0.016; Hz F3 p = 0.019; Hz F2 p = 0.021) and ischemic stroke (p = 0.001 for wrist Hz, wrist ROM, Hz F from 5 to F2; and ROM F1; ROM F3 p = 0.009; ROM F2 p = 0.010), and hemorrhagic cerebellum, improvement of parameters was observed. Stabilization of the upper limb and passive stabilization of the trunk improved the frequency and range of movements in the radiocarpal joint and in the fingers of patients after stroke, regardless of the type of stroke.

Functional Therapeutic Strategies Used in Different Stages of Alzheimer's Disease-A Systematic Review.

As Alzheimer's disease develops, the central nervous system is gradually damaged. It is manifested by progressive dementia and the appearance of neurological and extrapyramidal symptoms that impair everyday functioning. The aim of the study was to evaluate the influence of physical exercise on cognitive and motor functions in various stages of Alzheimer's disease. Methods: Four databases (PubMed, Scopus, Ovid, and Cochrane Library) were searched for relevant papers published between 2012 and May 2022. The works were assessed in terms of the adopted inclusion criteria. The measures of the results were changed in the parameters assessing motor and cognitive functions. Methodological quality was assessed using the Cochrane Collaboration. This review was recorded with the Cochrane Library: CRD42022340496. The results of the database search showed 302 articles, 12 of which were included in the review. All studies have shown a significant positive effect on improving cognitive and motor functions. This systematic review revealed a beneficial effect in improving cognitive and motor functions after the application of various kinds of activities, especially in the early and mild stages of Alzheimer's disease.

Screening diagnosis of dementia in patients following heart failure decompensation is associated with a higher relative wall thickness.

BACKGROUND: The usefulness of echocardiographic characteristics for dementia prediction in patients with heart failure decompensation (HFD) is not determined. Therefore, we sought to investigate the echocardiographic features of patients with HFD and screening diagnosis of dementia (SDD). METHODS: 139 patients aged over 65 years were hospitalized with the diagnosis of HFD. Clinical characteristics and echocardiographic characteristics were recorded during hospitalization. SDD was defined based on the result of ALFI- MMSE of <17 points. RESULTS: Patients with SDD were older (p=0.013), had thicker IVSd (p=0.021), thicker PWd (p=0.005) and had a higher RWT (0.40 vs 0.35, p=0.004) than patients without SDD, without differences in LVMI (p=0.13). There was no correlation between RWT and LVMI (r=-0.01, p=0.88). In the multivariate analysis, an older age (ß=-0.116, 95% CI -0.224 - -0.008, p=0.035, per year) and a higher RWT (ß=-0.069, 95% CI -0.137 - -0.002, p=0.045, per 0.01) influenced a lower ALFI-MMSE. For a prediction of SDD, the RWT reached the area under a ROC curve of 0.67 (95% CI 0.56-0.77, p=0.004 with sensitivity of 60% and specificity of 70% for RWT of ≥0.375). CONCLUSIONS: Apart from age, RWT reflecting left ventricular geometry changes but not hypertrophy was independently but moderately associated with SDD in patients following HFD (Tab. 4, Fig. 1, Ref. 35).

The Use of Armeo®Spring Device to Assess the Effect of Trunk Stabilization Exercises on the Functional Capabilities of the Upper Limb-An Observational Study of Patients after Stroke.

Almost half of stroke patients report impaired function of the upper limb and hand. Stability of the trunk is required for the proper movement of the body, including the legs and arms. The aim of the study was to analyze the effect of trunk stabilization exercises on coordinated movement of the affected upper limb in patients after stroke, using an Armoe®Spring device and the "wall" and "abacus" functional tests. Materials and methods: This is a randomized, double-blinded study. The research was carried out in the Rehabilitation Clinic on a group of 60 stroke patients who were randomly assigned to groups differing in the rehabilitation program. The study group had physiotherapy based on the NDT Bobath concept and the control group used classic exercises. The importance of the trunk for upper limb coordination was assessed on the Armeo®Spring device using three evaluation programs, "perpendicular fishing"; "horizontal fishing"; "reaction time", and two proprietary tests, "wall" and "abacus". Results: The post-treatment analysis showed significantly better results in the study group for the abacus (p < 0.001), wall (p = 0.003) tests, and a significantly higher percentage of task completion in the vertical fishing (p = 0.036) and reaction time (p = 0.009) tests. Conclusions: Physiotherapy including exercises to stabilize the trunk had a significant effect on increasing the functional efficiency of the affected upper limb and on improving the handgrip strength. The Armeo®Spring device is a good device for the functional assessment of the upper limb before and after therapy.

The Big Five Personality Traits and Positive Orientation in Polish Adults with Multiple Sclerosis: The Role of Meaning in Life.

Scientific achievements concerning the direct relation between personality traits and positive orientation among patients with multiple sclerosis do not explain the role of potential mediators. In fact, some researchers argue that the traits-positivity association is much more complex than it seems to be. For this reason, we made an attempt to analyze the indirect relationship between the above-mentioned variables, including meaning in life as a mediator. In total, 618 patients with MS took part in the study. The NEO Five-Factor Inventory, the Positive Orientation Scale, and the Meaning in Life Questionnaire were used. The results showed that positive orientation/the presence of meaning/searching for meaning correlated positively with extraversion, openness to experience, agreeableness, and conscientiousness, and were negatively associated with neuroticism. Moreover, meaning in life in both its dimensions acted as a mediator in 9 of 10 models. It can be assumed that a propensity to establish interpersonal relationships (extraversion), use active imagination (openness), inspire confidence among others (agreeableness), and take responsibility (conscientiousness) can have an impact on someone's positive attitude toward oneself and the surrounding world (positive orientation) when people have meaning in life and when they are seeking it.

Case Report of Cerebral Sinus Thrombosis Related to Immune Thrombotic Thrombocytopenia Following Administration of ChAdOx1 nCoV-19 for Vaccination against COVID-19.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) with cerebral venous sinus thrombosis (CVST) has been recently reported after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We present a case of a patient with fulminant CVST and thrombocytopenia after receiving the ChAdOx1 nCoV-19 vaccine. Although the patient received immediate anticoagulant and intravenous immune globulin treatment, he died within 24 h after hospital admission. VITT and CVST are rare conditions; however, the course may be fatal. Therefore, clinicians should be familiarized with the clinical and laboratory features of VITT.

Nocturnal non-dipping on 24-h Ambulatory Blood Pressure Monitoring in children and adolescents with obesity is associated with higher total cholesterol levels.

BACKGROUND: Few studies indicate the occurrence of abnormal nocturnal dipping of blood pressure (BP) in 35-50% of children and adolescents with obesity. The relation between that phenomenon and metabolic complications of obesity remains unclear. To evaluate the association between disorders of glucose and lipid metabolism, and nocturnal non-dipping in pediatric patients with obesity. METHODS: In 207 children (53.14% girls, mean age 14 (range 2-17), mean BMI Z-SCORE 4.38, range 2.07-10.74) standard 24-h Ambulatory Blood Pressure Monitoring was performed. Normal dipping was defined as a ≥ 10% decline in BP during the night. RESULTS: There were 106 (51.21%) cases of non-dippers. The mean 24-h nocturnal systolic BP (SBP) reduction (%) was 9.9 ± 5.5. The mean 24-h nocturnal diastolic BP (DBP) reduction (%) was 15.8 ± 8.5. There was a significant correlation between BMI Z-SCORE and mean day-time SBP (r = 0.14 P = .042). There are positive correlations between 24-h heart rate (beats/min) and BMI Z-SCORE (r = 0.15, P = .027), between fasting glucose and systolic BP Z-SCORE (r = 0.17, P = .03) and between mean diastolic BP and LDL cholesterol (r = 0.23, P = .004). Total cholesterol level was significantly higher in non-dippers (4.34 vs. 3.99 mmol/L, P = .034). There were no significant differences between non-dippers and dippers regarding fasting glucose (4.6 vs. 4.8 mmol/L), 120'post load glucose (5.7 vs. 5.9 mmol/L), insulin (19 vs. 20.2 µIU/mL), HOMA-IR (2.36 vs. 2.44), LDL cholesterol (2.64 vs. 2.51 mmol/L), HDL cholesterol (1.06 vs. 1.03 mmol/L) or triglycerides (1.36 vs. 1.34 mmol/L) levels. CONCLUSION: Nocturnal non-dipping is frequent in pediatric patients with obesity. It is associated with higher total cholesterol levels.