Introduction: Migraine prophylactic therapy has changed over recent years with the development and approval of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway. As new therapies emerged, leading headache societies have been providing guidelines on the initiation and escalation of such therapies. However, there is a lack of robust evidence looking at the duration of successful prophylaxis and the effects of therapy discontinuation. In this narrative review we explore both the biological and clinical rationale for prophylactic therapy discontinuation to provide a basis for clinical decision-making.Methods: Three different literature search strategies were conducted for this narrative review. These include i) stopping rules in comorbidities of migraine in which overlapping preventives are prescribed, notably depression and epilepsy; ii) stopping rules of oral treatment and botox; iii) stopping rules of antibodies targeting the CGRP (receptor). Keywords were utilized in the following databases: Embase, Medline ALL, Web of Science Core collection, Cochran Central Register of Controlled Trials, and Google Scholar.Discussion: Reasons to guide decision-making in stopping prophylactic migraine therapies include adverse events, efficacy failure, drug holiday following long-term administration, and patient-specific reasons. Certain guidelines contain both positive and negative stopping rules. Following withdrawal of migraine prophylaxis, migraine burden may return to pre-treatment level, remain unchanged, or lie somewhere in-between. The current suggestion to discontinue CGRP(-receptor) targeted mAbs after 6 to 12 months is based on expert opinion, as opposed to robust scientific evidence. Current guidelines advise the clinician to assess the success of CGRP(-receptor) targeted mAbs after three months. Based on excellent tolerability data and the absence of scientific data, we propose if no other reasons apply, to stop the use of mAbs when the number of migraine days decreases to four or fewer migraine days per month.There is a higher likelihood of developing side effects with oral migraine preventatives, and so we suggest stopping these drugs according to the national guidelines if they are well tolerated.Conclusion: Translational and basic studies are warranted to investigate the long-term effects of a preventive drug after its discontinuation, starting from what is known about the biology of migraine. In addition, observational studies and, eventually, clinical trials focusing on the effect of discontinuation of migraine prophylactic therapies, are essential to substantiate evidence-based recommendations on stopping rules for both oral preventives and CGRP(-receptor) targeted therapies in migraine.Graphical

The effect multiple sclerosis (MS) has on the social functioning and integration of patients has been recently considered as an important factor of the disease. To assess social participation of MS patients with regard to demographic and disease-related variables. The study comprised 201 MS patients: 140 women, 61 men, aged 24-69 years. The World Health Organization Disability Assessment Schedule (WHODAS 2.0) was applied to assess the aspects of social functioning and the Beck Depression Inventory (BDI) was applied to evaluate the level of depression. Disease duration, degree of disability in Expanded Disability Status Scale (EDSS), most disabling symptoms and type of treatment were determined. WHODAS 2.0 scores (total and within particular domains) and their relationships with age, gender, disease-related variables and level of depression were analyzed. The results of WHODAS 2.0 for 27.4% of patients exceeded the 90th percentile compared to the population norms (with the highest scores for "getting around" and "participation in society" domains). The results of BDI and WHODAS 2.0 were strongly correlated (p < 0.001; β = 0.73) and mobility impairment was related to both of them (p < 0.001; β = -0.12 and 0.25, respectively). Other disabling symptoms were associated with scores in domains "understanding and communicating", "getting around" and "participation in society". Social participation of the MS patients is affected by the impact of disease and associated with depression. Particular symptoms of neurological deficit (motor and visual impairment, fatigue) influence social functioning more than general disease-related variables.

Obstructive sleep apnea (OSA) is often accompanied by sleep bruxism (SB). A low respiratory arousal threshold (AT) may contribute to the induction or exacerbation of SB. The aim of this study was to assess the impact of the AT on the intensity of bruxism in individuals with OSA and SB. The prospective observational study was undertaken in 117 subjects with suspected sleep disorder (47% females, average age 44.83 years) who undergone video-polysomnography. Among the study participants, 77 (64.1%) were found to have a low AT, while 42 (35.9%) had a high AT. Participants with low AT’s had significantly higher bruxism episode index (BEI) and phasic BEI values than patients with a high AT (6.06 ± 4.46 vs. 4.54 ± 3.18; p = 0.04 and 3.18 ± 3.49 vs. 1.84 ± 1.74; p = 0.03, respectively). The positive correlation between BEI and a low AT and a higher percentage of hypopneas were found (R = 0.190, p = 0.040; R = 0.278, p = 0.002, respectively). Summarizing, there is a higher intensity of SB observed in patients with a low AT, than in those with a high one. This effect is more pronounced in men. SB accompanying low AT may be a protective factor in OSA patients, by terminating respiratory events. Thus patients with a low AT and SB could be better protected from OSA complications.

Background. Kidney diseases are the main causative factors of secondary hypertension (HTN) in children. Although primary HTN is less common in the pediatric population, its increasing prevalence, especially among teenagers, makes early diagnosis an emerging issue. Objectives. To analyze the potential differences between primary HTN and HTN secondary to renal diseases, in order to tailor diagnostic procedures to pediatric patients with suspicion of HTN. Material and methods. A retrospective evaluation was performed of medical records of 168 children (aged from 1 month to 18 years) diagnosed with arterial HTN in the Pediatric Nephrology Department of Wroclaw Medical University (Poland). The comparative analysis concerned demographics, causes of HTN, clinical picture, laboratory tests, and parameters of ambulatory blood pressure monitoring (ABPM). Results. Out of 168 children, 47% were diagnosed with primary HTN and 53% with secondary renal HTN. The patients with primary HTN were significantly older than those with HTN secondary to renal disease. Among the children with primary HTN, 26% were overweight and 42% were obese; among those with renal HTN, the proportions were 16% and 19%, respectively. The patients with primary HTN had significantly higher body mass index (BMI) percentiles and z-scores, and tended toward higher pulse pressure (PP) values. In the group with secondary HTN, ABPM parameters of diastolic blood pressure (DBP) and total cholesterol were significantly elevated. The BMI z-scores correlated positively with PP in the whole group. Conclusions. As expected, HTN secondary to renal disease prevails in younger children, but primary HTN has become an emerging issue in teenagers. The diagnostics of HTN secondary to kidney disease have revealed risk factors worsening the prognosis, including higher values of cholesterol or of parameters connected with DBP. Primary HTN risk factors include obesity and a tendency towards higher PP values.

Introduction: Brain metastases are common and devastating complication of the lung cancer (LC) but predictive biomarkers for their risk are still lacking.Objectives: To analyze the relationships between complete blood count (CBC)-based and selected biochemical indices and occurrence of brain metastases in patients diagnosed with LC.Patients and methods: The study was based on retrospective analysis of medical records of 217 patients diagnosed with LC and undergoing follow-up in one specialist center. Clinical and laboratory data on admission were determined, including: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-platelet ratio (NPR) and red cell distribution width-to-platelet ratio (RPR) and selected biochemical parameters. Relationships were evaluated between these parameters and occurrence of brain metastases, other distant metastases and death within 12 months of follow-up.Results: 168 patients had the follow-up data for 6 months, and 128 - for 12 months. Brain metastases were detected in 41 patients and 1-year mortality rate was 17.61%. Patients who developed brain metastases during 12 months had significantly higher baseline NLR (4.66 vs 2.75, p<0.001), PLR (170.83 vs 142.42, p=0.03) and lower LMR (1.61 vs 2.33, p=0.008).In univariate analysis, higher leukocyte count (HR 1.08, p=0.016), neutrophil count (HR 1.11, p=0.0036), NLR (HR 1.09, p=0.005), d-dimer levels (HR 1.0002, p=0.0043), and lower LMR (HR 0.67, p=0.018) were significantly associated with the risk of developing brain metastases. Liver metastases were associated with lower LMR (1.69 vs 2.29, p=0.04), while metastases to the other lung – with lower PLR (126.52 vs 161.8, p=0.02) and higher LMR (2.51 vs 1.96, p=0.02) and RPR (0.184 vs 0.154, p=0.03). No significant relationships were found between CBC-based indices and mortality.Conclusions: CBC-based indices could be useful and easily accessible predictive markers of brain metastases in the patients with lung cancer.

Lung cancer is one of the most common neoplasms and the leading cause of cancer-related deaths worldwide. Despite recent progress in understanding the pathomechanisms of lung cancer, it is frequently associated with late diagnosis, high incidence of metastases and poor response to treatment. Thus, there is extensive research in the field of biomarkers that aims to optimize management of lung cancer. The aim of this study was to review the current perspectives of a wide spectrum of circulating molecules that seem promising as new potential biomarkers of lung cancer. Among these, biochemical (active proteins), immunological (immunocompetent cells, cytokines, chemokines, and antibodies) and genetic (circulating tumor DNA, cell-free DNA and microRNA) markers are presented and discussed. The use of these markers would support the early detection of lung cancer and might be used for predicting disease progression, response of the disease to targeted therapies, monitoring the course of treatment, and developing individualized diagnostic and therapeutic strategies. Special attention was given to potential markers of nervous system involvement in the course of lung cancer, due to its prevalence and devastating impact. Limitations of the potential biomarkers are also outlined and future directions of investigations in this field highlighted, with the aim of improving the accuracy and practical utility of these biomarkers.