Oral Cladribine in Patients who Change From First-Line Disease Modifying Treatments for Multiple Sclerosis: Protocol of a Prospective Effectiveness and Safety Study (CLAD CROSS).

Background: Recently, the number of available disease modifying therapies for multiple sclerosis (MS) has increased. However, a proportion of patients treated with these agents continue to experience relapses and disease progression. Cladribine tablets, approved in 2017 for highly active relapsing MS, comprise a sparsely administered oral treatment which exerts its therapeutic effect through a reduction and subsequent repletion of the lymphocyte population. Purpose/Study Sample: Here we describe the design of CLAD CROSS, a prospective, non-interventional, multicenter, Phase IV study in patients with a confirmed diagnosis of RRMS who switch from first-line disease modifying drugs (DMDs) to treatment with cladribine tablets in routine clinical practice. 242 adult patients will be recruited in 61 sites (6 countries) over 30 months and will be followed up for 2 years following prescription of cladribine tablets per the decision of the treating physicians. Research Design: The primary endpoint is the change in annualized relapse rate (ARR) between the 12-month pre-baseline period and over the 12-month period before end of study. Secondary endpoints are the percentage of patients with 6-month disability progression or improvement at the end of the study, measured by the Expanded Disability Status Scale, Timed 25 Foot Walk and 9-Hole Peg Test scales and quality of life, treatment satisfaction, and healthcare resource utilization, measured through the MSIS-29, TSQM 1.4, and EQ-5D-3L scales, respectively. MRI lesions will be compared in the exploratory setting between the 12-month pre-baseline period, baseline, and at years 1 and 2. Adverse events will be monitored throughout the study. Interim analyses are pre-planned when 30% and 60% of patients will complete the 12-month follow-up visit. Conclusions: CLAD CROSS will provide efficacy data on cladribine tablets, used as a follow-up treatment to first-line DMDs in the real-world setting, will further establish its safety profile and will collect information to support pharmacoeconomic studies.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in the Russian Population.

OBJECTIVE: Cognitive dysfunction is common in multiple sclerosis (MS). The Brief International Cognitive Assessment for MS (BICAMS) battery of tests has been suggested as a measure for the evaluation of the cognitive status of MS patients. This study aims to validate the BICAMS battery in the Russian population of MS patients. METHODS: Age- and sex-matched MS patients (n = 98) and healthy individuals (n = 86) were included in the study. Symbol Digit Modalities Test (SDMT), California Verbal Learning Test, 2nd edition (CVLT-II) and the Brief Visuospatial Memory Test - Revised (BVMT-R) were administered to all participants. The battery was readministered 1 month later to 44 MS patients to investigate the test-retest reliability. RESULTS: MS patients exhibited a significantly lower performance in testing with BICAMS than the control group in all three neuropsychological tests. Test-retest reliability was good for SDMT and CVLT-II (r = .82 and r = .85, respectively) and adequate for BVMT-R (r = .70). Based on the proposed criterion for impairment as z score below 1.5 SD the mean of the control group, we found that 34/98 (35%) of MS patients were found impaired at least in one cognitive domain. Patients with Expanded Disability Status Scale score ≥3.5 performed significantly worse than controls (SDMT, p < .0001; CVLT-II, p = .03; BVMT-R, p = .0004), while those with ≤3.0 scores did not. CONCLUSION: This study demonstrates that the BICAMS battery is a valid instrument to identify cognitive impairment in MS patients and it can be recommended for routine use in the Russian Federation.

Association of TNFα, TNFR1, and TNFR2 polymorphisms with sperm concentration and motility.

Tumor necrosis factor α (TNFα) is a multifunctional cytokine that regulates various cellular processes related to spermatogenesis. Two types of cell receptors, TNFR1 and TNFR2, mediate TNFα activity. In the present study, we sought to explore the association of TNFα -857C→T, TNFR1 36A→G, and TNFR2 676T→G polymorphisms with sperm concentration and motility. Two hundred ninety men were examined during infertility investigation; of those, 170 men were normozoospermic and 120 were oligospermic. Polymerase chain reaction analysis revealed significant differences in genotype distribution of the TNFR1 36A→G polymorphism between normozoospermic and oligospermic men. Men with oligozoospermia presented TNFR1 36A/A genotypes less frequently than normozoospermic men (P < .001). The presence of the TNFR1 36G allele was significantly increased in oligospermic men (P < .001). Furthermore, the presence of the TNFR1 36G allele was associated with lower sperm concentration in normozoospermic men (P < .03) and in the total study population (P < .001), and with lower sperm motility in normozoospermic men (P < .007) and in the total study population (P < .001). No significant associations were found between TNFα -857C→T and TNFR2 676T→G polymorphisms and semen quality. The TNFR1 36A allele is associated with increased sperm concentration and motility in our series, supporting the significance of TNFR1 gene in semen quality.

Huge intrathyroidal hematoma causing airway obstruction: a multidisciplinary challenge.

Thyroid hemorrhage is a relatively frequent event that in most cases causes pain and discomfort only, while rarely can cause significant neck swelling. Even more rarely, however, extensive thyroid hemorrhage can result in a rapidly expanding hematoma with airway compromise. We report a case of a rapidly expanding thyroid hemorrhage that occurred secondary to oral anticoagulation therapy in an 80-year-old patient with a previously existing goiter. The patient presented with acute onset of neck pain, dysphagia, and respiratory distress caused by tracheal compression from the thyroid mass. Computed tomography demonstrated a 6 x 9 x 10 cm mass consistent with an intrathyroidal hematoma projecting into the anterior mediastinum and displacing the trachea to the left. Rapid reversal of the coagulopathy was achieved with fresh frozen plasma and vitamin K. Consequently, the patient was managed conservatively with close observation, antibiotics, and steroids because no progression of airway compromise was manifested. Although the diagnosis can be easily established in these patients, no management guidelines of this condition exist. The potential of rapid airway compromise and the risk for exacerbation of bleeding in the light of significant elevation in the international normalized ratio (INR), make any airway management decisions very difficult. The importance of managing the airway and the haemostatic problem with the help of a multidisciplinary team is discussed.