Immediate Unilateral Subpectoral Implant-Based Breast Reconstruction does not Impair Pulmonary Functions: A Preliminary Prospective Study.

BACKGROUND: Implant-based breast reconstruction is one of the most common procedures among women with breast cancer undergoing mastectomy. Prosthetic devices may be positioned either beneath or above the pectoralis major muscle, which is considered an accessory muscle of ventilation. This preliminary prospective study aimed to investigate whether subpectoral unilateral implant-based breast reconstruction has any effect on patients' pulmonary functions. METHODS: A prospective study of fourteen women who underwent immediate unilateral implant-based subpectoral breast reconstruction by a single surgeon over 10 months was conducted. Spirometry and maximal voluntary ventilation tests were conducted 1 day prior to surgery, and 1- and 3 months following breast reconstruction. ANOVA or Friedman test were used to compare pulmonary function tests before and after surgery. RESULTS: Fourteen patients completed the study protocol. No statistically significant differences were found when comparing spirometry parameters in the three time points. CONCLUSIONS: Pectoralis muscle release does not impair pulmonary function among patients undergoing immediate unilateral implant-based breast reconstruction following mastectomy. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Safety of troclosene sodium solution in decontamination of wounds: A prospective clinical and laboratory study.

Debate persists regarding the safety of hypochlorite-containing solutions in the decontamination of infected wounds. In 2006, the Israeli Ministry of Health withdrew licensing approval for troclosene sodium as a wound irrigation solution. The aim of this prospective clinical and laboratory study was to investigate the safety of troclosene sodium solution for decontamination of infected wounds. Troclosene sodium solution was used to treat 30 patients with 35 infected skin wounds of various etiologies and body areas, over a treatment period of 8 days. Data were gathered according to a prospectively designed protocol including general findings, wound-specific observations on Day 1 and Day 8 and laboratory parameters on Day 1 and Day 8. Wound swabs and tissue biopsy for culture were taken on Day 1 and Day 8. Statistical analysis was executed. Tests were 2-sided and p values of <0.05 were considered statistically significant. Eighteen males and 12 females, with 35 infected skin wounds were enrolled. There were no adverse clinical events. No significant changes were observed in general clinical observations. Statistically significant improvements were observed in: pain (p < 0.0001); edema (p < 0.0001); area of wound covered by granulation tissue (p < 0.0001); exudate (p < 0.0001); and erythema (p = 0.002). Prior to treatment, bacteria were demonstrated on microscopy or on culture in 90% of wound samples. On Day 8, this frequency reduced to 40%. There were no abnormal laboratory tests. Serum sodium concentration increased significantly between Day 1 and Day 8, whilst serum concentration of urea and concentrations of thrombocytes, leucocytes and neutrophils showed statistically significant reductions, but all values remained within normal laboratory ranges throughout the study period. Troclosene sodium solution is clinically safe in the management of infected wounds. These findings were presented to the Israel Ministry of Health and as a result, troclosene sodium was re-approved and licensed for decontamination of infected wounds in Israel.

Bridging Care Transition After Hospitalization for Atrial Fibrillation and Coronary Interventions.

ABSTRACT: Treatment fragmentation between hospitals and the community can result in catastrophic outcomes; uninterrupted treatment with anticoagulant and platelet aggregation inhibitors is particularly important. We assessed the proportion and characteristics of patients who did not visit their primary community-based physician within 1 week of discharge from our department of cardiovascular medicine and the proportion that failed to procure essential drugs at the community pharmacy. We prospectively studied 423 patients who were discharged from our department. They were provided detailed explanations, tablets for 7 days, prescriptions, and a printed drug plan. We traced the time from discharge until a visit with a primary community-based physician, and the time until the procurement of medications, using our computerized community-hospital-integrated system. Complete data were available for 313 patients, of whom 220 were treated with anticoagulants or platelet aggregation inhibitors. For 175 patients, these drugs were initiated during index hospitalizations. Only 1 patient did not receive platelet aggregation inhibitors despite recommendations. Seventy-nine patients (25%) first visited their primary care physicians more than 1 week after discharge. Predictors for delayed visits were living alone (hazard ratio 1.91) and having an in-house caregiver (hazard ratio 2.01). In conclusion, all but 1 patient continued drug therapy after discharge from the hospital. The simple predischarge steps included patient education and provision of a 1-week supply of tablets and prescriptions. Treatment continuation was independent of visits to the community-based primary physician. Patients living alone or with an in-house caregiver more often delayed visits to primary physicians yet continued relevant drug therapy.

Ischemic stroke and myocardial ischemia in clopidogrel users and the association with CYP2C19 loss-of-function homozygocity: a real-world study.

Reduced clopidogrel effectiveness in preventing recurrent myocardial ischemia following percutaneous coronary intervention has been demonstrated in CYP2C19 loss-of-function carriers. Less is known about the effect of CYP2C19 genotype on the effectiveness of clopidogrel for stroke prevention, particularly in Caucasians. This is a retrospective cohort study, in which we used the Clalit clinical database to follow genotyped clopidogrel initiators, for up to 3 years. Endpoint was a new primary discharge diagnosis of ischemic stroke; secondary endpoints were new primary discharge diagnoses of coronary angioplasty, myocardial infarction (MI), or a composite endpoint of: stroke, MI, or coronary angioplasty. After 3 years of follow up over 628 clopidogrel initiators, 2 out of 12 (16.7%) poor metabolizers, 9 out of 144 intermediate metabolizers (6.3%), and 29 out of 472 (6.1%) normal/rapid/ultrarapid metabolizers have been newly diagnosed with ischemic stroke. Poor metabolizer status was associated with higher risk for ischemic stroke, marginally significant in univariate analysis and in multivariable models; and higher risk for the composite outcome of stroke, myocardial infarction and coronary angioplasty, HR = 3.32 (1.35-8.17) p = 0.009, 2.86 (1.16-7.06) p = 0.02 (univariate and multivariate analyses, respectively). Poor metabolizer status was associated with higher risk for stroke HR = 5.80 (1.33-25.24) p = 0.019, HR = 4.13 (0.94-18.13) p = 0.06 (univariate and multivariate analyses, respectively) in patients who "survived" the first year, and were in the cohort 1-3 years. Caucasian treated with clopidogrel who are homozygote for the CYP2C19 loss-of function allele might be at increased risk for ischemic stroke, and for the composite outcome of ischemic stroke, myocardial infarction and coronary angioplasty.

Beliefs about medication as predictors of medication adherence in a prospective cohort study among persons with multiple sclerosis.

BACKGROUND: Though adherence to disease-modifying therapies (DMTs) among persons with multiple sclerosis (PwMS) varies and is often below 80%, only few prospective studies on adherence examined predictors beyond demographic and clinical characteristics. OBJECTIVES: Identify antecedents to adherence and persistence to DMT in a prospective design among PwMS. METHODS: PwMS (n = 186) were prospectively assessed at three time points: baseline, 6 (Time 1) and 12 months later (Time 2). Clinical, demographic information and patient-reported medication beliefs, illness perceptions, medication habits, perceived health and affect were surveyed in-person. Adherence and persistence were assessed by a combination of self-reports and retrospective review of medication claims. FINDINGS: PwMS were 69.9% (Time 1) and 71% (Time 2) adherent to their DMTs and 64.5.9% were persistent. Beliefs about Medications were consistently predictive at both time points (baseline to Time 1 and Time 1 to Time 2) of medication adherence and persistence whereas other perceptions were predictive in some analyses; clinical and demographic characteristics were mostly not predictive of adherence nor persistence. The prospective association of beliefs about medication with adherence held also in multivariate analyses (OR = 0.88, 95% CI 0.78-0.99, p = 0.029). CONCLUSIONS: Adherence and persistence are predicted by medication beliefs of PwMS. As medication beliefs are modifiable, they should be assessed periodically and targeted as a focus of tailored interventions aimed to improve adherence and consequently health outcomes in PwMS. REGISTRATION: Clinical trials registry # NCT02488343 , date: 06/08/2015.

Global longitudinal strain and long-term outcome in patients presenting to the emergency department with suspected acute coronary syndrome.

AIMS: We have previously shown that 2-dimentional strain is not a useful tool for ruling out acute coronary syndrome (ACS) in the emergency department (ED). The aim of the present study was to determine whether in patients with suspected ACS, global longitudinal strain (GLS), measured in the ED using 2-dimensional strain imaging, can predict long-term outcome. METHODS: Long-term (median 7.7 years [IQR 6.7-8.2]) major adverse cardiac events (MACE; cardiac death, ACS, revascularization, hospitalization for heart failure, or atrial fibrillation) and all-cause mortality data were available in 525/605 patients (87%) enrolled in the Two-Dimensional Strain for Diagnosing Chest Pain in the Emergency Room (2DSPER) study. The study prospectively enrolled patients presenting to the ED with chest pain and suspected ACS but without a diagnostic ECG or elevated troponin. GLS was computed using echocardiograms performed within 24 hours of chest pain. MACE of patients with worse GLS (>median GLS) were compared to patients with better GLS (≤ median GLS). RESULTS: Median GLS was -18.7%. MACE occurred in 47/261 (18%) of patients with worse GLS as compared with 45/264 (17%) with better GLS, adjusted HR 0.87 (95% CI 0.57-1.33, P = .57). There was no significant difference in all-cause mortality or individual endpoints between groups. GLS did not predict MACE even in patients with optimal 2-dimensional image quality (n = 164, adjusted HR=1.51, 95% CI 0.76-3.0). CONCLUSIONS: Global longitudinal strain did not predict long-term outcome in patients presenting to the ED with chest pain and suspected ACS, supporting our findings in the 2DSPER study.

Survival of Patients with Chronic Total Occlusion of the Right Coronary Artery.

BACKGROUND: The impact of revascularization of coronary chronic total occlusion (CTO) on survival is unknown. Several studies, which included subjects with varied coronary anatomy, suggested that CTO revascularization improved survival. However, the contribution of CTO revascularization to improved outcome is unclear since it was more commonly achieved in subjects with fewer co-morbidities and less extensive coronary disease. OBJECTIVES: To study the association between CTO revascularization and survival in patients with uniform coronary anatomy consisting of isolated CTO of the right coronary artery (RCA). METHODS: A registry of 16,832 coronary angiograms was analyzed. We identified 278 patients (1.7%) with isolated CTO of the RCA who did not have lesions within the left coronary artery for which revascularization was indicated. Survival of 52 patients (19%) who underwent successful percutaneous coronary intervention was compared to those who did not receive revascularization. RESULTS: Revascularized patients were younger (60.2 vs. 66.3 years, P = 0.001), had higher creatinine clearance (106 vs. 83 ml/min, P < 0.0001), and had fewer co-morbidities than those who did not receive revascularization. Lack of CTO revascularization was a univariable predictor of mortality (hazard ratio [HR] = 2.65, 95% confidence interval [95%CI] 1.06-6.4) over 4.3 ± 2.5 years of follow-up. On multivariable analysis, the only predictors of mortality were increased age (HR 1.04, 95%CI 1.01-1.07), reduced creatinine clearance (HR 1.02, 95%CI 1.01-1.03), and ejection fraction below 55% (HR 2.24, 95%CI 1.22-4.11). CONCLUSIONS: Among patients with isolated RCA CTO who underwent extended follow-up, revascularization was not an independent predictor of increased survival.

ß2-adrenoceptor agonists and antagonists and risk of Parkinson's disease.

BACKGROUND: ß2-adrenoreceptors have recently been identified as regulators of the α-synuclein gene, which is implicated in the pathogenesis of Parkinson's disease. OBJECTIVE: The objectives of this study were to assess the association between use of ß2-agonists and ß-antagonists and the risk of developing PD. METHODS: We conducted a nested case-control study in a cohort of 1,762,164 adults without a diagnosis of PD. They were identified on January, 1, 2004, from the electronic medical records of the largest health care provider in Israel. Participants were followed up until June 30, 2017, for the occurrence of PD. Ten randomly selected controls were matched to each case of PD on age, sex, ethnic group, and duration of follow-up. RESULTS: During follow-up 11,314 patients were newly diagnosed with PD and were matched with 113,140 controls. An increased risk of PD was seen with the use of nonselective ß-antagonists (RR, 2.04 [1.90-2.20]) but not with the use of selective ß1-antagonists (RR, 1.00 [0.95-1.05]). Use of ß2-agonists was associated with reduced risk of PD (RR, 0.89 [0.82-0.96] for short-acting; RR, 0.84 [0.76-0.93] for long-acting; and RR, 0.49 [0.25-0.92] for ultra-long-acting ß2-agonists). In an analysis of individual drugs, propranolol and salbutamol were significantly associated with PD risk, even when these drugs were ascertained 5 years prior to the index date, compared with nonusers (RR, 1.31 [1.08-1.58] and 1.89 {1.53-2.33]) in patients who filled <6 and ≥6 propranolol prescriptions, respectively; the corresponding RRs for salbutamol were 0.95 (0.83-1.08) and 0.65 (0.45-0.94), respectively. CONCLUSIONS: Use of propranolol appears to be associated with an increased risk of PD, whereas use of ß2-agonists is associated with a decreased risk of PD. © 2018 International Parkinson and Movement Disorder Society.

The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis.

BACKGROUND: The association between subjective cognitive fatigue and objective cognitive dysfunction in patients with multiple sclerosis (PwMS) has been studied, with conflicting results. OBJECTIVE: To explore the impact of fatigue on cognitive function, while controlling for the influence of depression, disability, comorbidities, and psychotropic medications. METHODS: PwMS completed a computerized cognitive testing battery with age- and education-adjusted cognitive domain scores. Disability (Expanded Disability Status Scale (EDSS)), cognitive fatigue, and depression were concurrently evaluated. RESULTS: In all, 699 PwMS were included. Both cognitive fatigue and depression were significantly and negatively correlated with the same cognitive domains: information processing speed, executive function, attention, motor function, and memory (-0.15 ⩽ r ⩽ -0.14 for cognitive fatigue; -0.24 ⩽ r ⩽ -0.19 for depression). Multivariate analysis revealed significant but small independent correlations only between depression and neuropsychological test results, while cognitive fatigue had no independent correlation with objective cognitive function except for a trend toward impaired motor function in highly fatigued PwMS. Depression and cognitive fatigue accounted for no more than 6% of the variance in objective cognitive domain scores. CONCLUSION: Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.

How to Best Predict Fragility Fractures: An Update and Systematic Review.

BACKGROUND: Because fragility fractures have an enormous impact on the practice of medicine and global health systems, effective screening is imperative. Currently, dual-energy X-ray absorptiometry (DXA), which has limited ability to predict fractures, is being used. We evaluated the current literature for a method that may constitute a better screening method to predict fragility fractures. A systematic review of the literature was conducted on computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound to evaluate screening methods to predict fragility fractures. We found that ultrasound had sufficient data on fracture prediction to perform meta-analysis; therefore, we analyzed prospective ultrasound cohort studies. Six study populations, consisting of 29,299 individuals (87,296 person-years of observation) and including 992 fractures, were analyzed. MRI was found to be sensitive and specific for osteoporosis, but its use for screening has not been sufficiently evaluated and more research is needed on cost, accessibility, technical challenges, and sensitivity and specificity. CT could predict fracture occurrence; however, it may be problematic for screening due to cost, exposure to radiation, and availability. Ultrasound was found to predict fracture occurrence with an increased risk of 1.45 (95% confidence interval 1.21-1.73) to fracture. Ultrasound has not replaced DXA as a screening tool for osteoporosis, perhaps due to operator-dependency and difficulty in standardization of testing.

[THE CLINICAL AND DEMOGRAPHIC CHARACTERISTICS OF PATIENTS WHO FREQUENT THE PSYCHIATRIC EMERGENCY ROOM IN A GENERAL HOSPITAL].

INTRODUCTION: The recent policy implemented in Israel of reducing psychiatric admissions and the concomitant shifting of treatment to outpatient clinics, together with briefer stays in hospital and a growing number of repeat emergency room (ER) visits have created a "revolving door" phenomenon, whereby a small number of frequent attenders are responsible for a disproportionate fraction of ER visits. OBJECTIVES: To characterize psychiatric ER frequent attenders and understand their special needs by analyzing the "revolving door" phenomenon and defining the at-risk group. METHODS: Psychiatric attenders at the Ha'Emek Medical Center in Afula during a single year were divided retrospectively into three groups according to the number of their visits to the ER. One group had a single ER visit, an intermediate group had two to three ER visits, and a third group had four or more ER visits (frequent attenders). The groups were weighted by the respective number of attenders and analyzed using the optimal allocation technique. RESULTS AND CONCLUSIONS: The findings showed that people prone to frequently repeat visits to a psychiatric emergency room are familiar with the psychiatric system, unemployed, with an unstable income (or recipients of an allowance from the National Insurance), single or divorced, of Sephardic origin, have been hospitalized in the past, and are urban, native-born with social and family problems. From a clinical perspective the findings also showed thatthis subgroup comes to the ER without a referral, suffers from depression and psychotic states, personality disorders or mental retardation, has past suicide attempts, and the patients are under medication treatment. DISCUSSION AND SUMMARY: Frequent attenders make up a particularly difficult group of patients with major psychiatric disorders. The ER is not a fit setting for the treatment of such patients. The construction of a proper therapist-patient relationship is cardinal to attaining a meaningful remission. Prompt recognition of frequent attenders and their respective visiting pattern is required, allowing for a structured therapeutic approach which will include patient and family guidance and an algorithmic handling of emergency situations.

Retinal nerve fibre layer thickness measurements by optical coherence tomography in patients with sleep apnoea syndrome.

BACKGROUND: The study aims to investigate whether retinal nerve fibre layer (RNFL) abnormalities can be detected in patients with obstructive sleep apnoea/hypopnoea syndrome with normally appearing optic disc. DESIGN: This is an observational case-control study. PARTICIPANTS: One hundred and eight consecutive patients with moderate or severe obstructive sleep apnoea/hypopnoea syndrome (OSAHS) as determined by overnight polysomnography and normal looking discs and 108 age-matched healthy controls were included in the study. METHODS: All patients underwent RNFL examinations by optical coherence tomography using fast retinal nerve fibre layer thickness scan. MAIN OUTCOME MEASURES: The main outcome measure was RNFL thickness. RESULTS: Multivariate regression analysis results showed that the RNFL was thinner for a patient with OSAHS than that of a normal control in the average by 4.20 µm (P < 0.003), in the superior quadrant by 4.83 µm (P = 0.028) and in the inferior quadrant by 5.19 µm (P = 0.016). RNFL thickness did not correlate with the severity of the disease. CONCLUSIONS: RNFL thinning was detected in normal-looking discs of patients with advanced OSAHS, but the extent of this thinning did not correlate with the severity of the disease. Longitudinal follow-up is needed to clarify whether RNFL thinning in OSAHS patients with normal clinically appearing optic nerves will eventually lead to glaucoma.

Personalized Intervention to Improve Medication Adherence for Persons with Multiple Sclerosis.

Purpose: To evaluate the acceptability, retention, and efficacy of face-to-face intervention, incorporating education and Motivational Interviewing (MI) to support persons with relapsing-remitting multiple sclerosis (PwRRMS) and increase self-reported medication adherence. Patients and Methods: PwRRMS (N = 60) prescribed Disease Modifying Treatment (DMT), who were identified as non-adherent and consented to participate in an intervention, received verbal education and counseling from their treating physician, a tailored MI counseling and a booster session via telephone with a health psychologist, and a concluding MI counseling six months later. Each PwRRMS filled a battery of patient-reported outcomes (PROs) at baseline, six and 12 months later. The design was a quasi-experimental pre-test post-test across a year. Results: Of the sixty identified persons who consented to enroll, 52 completed the intervention and 46 completed the follow-up. At six months following the baseline, adherence scores increased (median = 12.0) and were significantly different than at baseline (median=10.0, p = 0.030). Still, at 12 months follow-up there was no significant difference from baseline in reported adherence (median = 11.0, p = 0.106). Conclusion: This study demonstrated reasonable retention and initial efficacy of a combined psycho-education and MI protocol for PwRRMS to enhance medication adherence to DMT. To maintain the change, a more sustained intervention is required.

The study focused on persons with relapsing-remitting multiple sclerosis (PwRRMS) who do not adhere to their prescribed medication. Following the identification of non-adherent persons, PwRRMS were offered an intervention to increase their adherence. The study examined how many of those identified consented to enroll in the intervention, how many remained in the intervention, and whether the intervention was efficacious in terms of self-reported adherence. The intervention included verbal education and counseling from the treating physician, immediately followed by tailored counseling by a psychologist. There was a booster session via telephone with the psychologist, and a concluding counseling meeting six months later. Participants were followed for a year after the initial counseling. Two-thirds of PWMS identified as non-adherent consented to enroll (n = 60), 52 completed the intervention and 46 completed the follow-up. At six months following counseling, self-reported adherence scores significantly increased, but at 12 months follow-up there was no significant difference from baseline in reported adherence. To maintain the change, a more sustained intervention is required.

The thrombophilic network of autoantibodies in celiac disease.

BACKGROUND: Celiac disease is a life-long autoimmune condition, affecting genetically susceptible individuals that may present with thromboembolic phenomena. This thrombophilia represents a puzzle with multiple constituents: hyperhomocysteinemia, B12 and\or folate deficiency, methylenetetrahydrofolate reductase mutations, and protein C and S deficiency due to vitamin K deficiency. However, the well known thrombogenic factors, antiphosphatidylserine/prothrombin and antiprothrombin have never been explored in celiac disease. METHODS: The serum autoantibody levels were determined in 248 individuals, classified into three groups. Group 1 comprised 70 children with definitive celiac disease (age: 7.04 ±4.3 years, male to female ratio 1.06) and group 2 comprised 88 normal children (age: 6.7 ±4.17 years, male to female ratio 0.87), representing controls. The pediatric populations were compared to group 3, which included 90 adults who were family members (parents) of group 1 (age: 34.6 ±11.35 years, male to female ratio 1.2). Antibodies were checked by enzyme-linked immunosorbent assay. RESULTS: Mean optical density levels of serum antiphosphatidylserine/prothrombin immunoglobulin G antibodies were 32.4 ±19.4, 3.6 ±2.5 and 16.1 ±15.8 absorbance units in groups 1, 2 and 3 respectively (P <0.0001), with 45.7%, 0% and 7.8% of groups 1, 2 and 3 respectively positive for the antibody (P <0.01). Mean optical density levels of serum antiphosphatidylserine/prothrombin immunoglobulin M antibodies were 14.2 ±8.7, 6.7 ±6.4 and 12.4 ±15.5 absorbance units in groups 1, 2 and 3 respectively (P <0.0001), with 7.1%, 3.4% and 9.9% of groups 1, 2 and 3 positive for the antibody. Mean optical density levels of serum antiprothrombin and antiphospholipid immunoglobulin G antibodies were higher in groups 1 and 3 compared with 2 (P <0.005) and in groups 1 and 2 compared with 3 (P <0.01), respectively. Groups 1, 2 and 3 were positive for antiphospholipid immunoglobulin G antibodies (groups 1 and 2 compared with 3) . Celiac disease sera harbor a higher antiprothrombin immunoglobulin G level compared with controls. CONCLUSIONS: It is suggested that the intestinal injury, endothelial dysfunction, platelet abnormality and enhanced apoptosis recently described in celiac disease are at the origin of the increased exposure of phospholipids or new epitopes representing autoantigens. Those autoantibodies might play a pathogenic role in the thrombophilia associated with celiac disease and represent markers for potential anticoagulant preventive therapy.

The influence of vitamin D supplementation on melatonin status in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) incidence is higher in geographic regions with less sunlight exposure. Both vitamin D and melatonin are essential mediators of the effect of sunlight in health, and as such are candidates to play a key role in MS. We hypothesized that vitamin D and melatonin may have related influences in patients with MS. METHODS: In a randomized, double blind study of 40 IFN-ß treated MS patients, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 19 patients received 4,370 IU vitamin D3 per day (high dose) for one year. Serum 25-hydroxy-vitamin-D (25-OH-D) and nighttime urine melatonin metabolite, 6-sulphatoxy-melatonin (6-SMT), were measured at baseline, 3 months and 1 year from enrolment. RESULTS: After 3 months supplementation, 25-OH-D levels increased and nighttime melatonin secretion decreased significantly in the high dose group, but not in the low dose group. After 1 year, a decrease in 25-OH-D levels, accompanied by an increase of urine nighttime 6-SMT were observed in the high dose group. Percent change in serum 25-OH-D was significantly and negatively correlated with percent change in urine 6-SMT after 3 months and between 3 months to 1 year. 25-OH-D levels by the end of the study were significantly and negatively correlated to BMI. CONCLUSIONS: Melatonin secretion is negatively correlated with alterations in serum 25-OH-D in IFN-ß treated patients with MS. The finding suggests that melatonin should be considered as a potential mediator of vitamin D neuro-immunomodulatory effects in patients with MS.

Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties.

BACKGROUND: Flu-like symptoms (FLS) are common side effects of interferon beta (IFN-ß) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines' levels. METHODS: In a randomized, double blind study of 45 IFNß-treated PwMS, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 24 patients received 4,370 IU per day (high dose) for one year. FLS were assessed monthly by telephonic interviews. Serum levels of 25-hydroxy-D (25-OH-D), calcium, PTH, IL-17, IL-10 and IFN-γ were measured periodically. EDSS, relapses, adverse events and quality of life (QoL) were documented. RESULTS: 25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group. There was no significant change in FLS. IL-17 levels were significantly increased in the low dose group, while patients receiving high dose vitamin D had a heterogeneous IL-17 response. No significant differences in relapse rate, EDSS, QoL, serum IL-10 and IFNγ were found. Hypercalcemia or other potential major adverse events were not observed. CONCLUSION: Vitamin D supplementation to IFN-ß treated PwMS, at the doses used, seems safe and associated with dose-dependent changes in IL-17 serum levels, while not affecting IFN-ß related FLS. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01005095.

Predictors and Long-Term Prognostic Significance of Acute Renal Function Change in Patients Who Underwent Surgical Aortic Valve Replacement.

There are few reports on short-term changes in renal function after surgical aortic valve replacement, and data are scarce regarding its impact on long-term outcomes. This is a retrospective study of patients who underwent isolated aortic valve replacement between 2009 and 2020 in four medical centers. Patients with end-stage renal disease were excluded. Renal function was assessed based on short-term changes. Multivariable regression models were used to identify predictors of improvement/deterioration. Cox proportional hazard models were used to assess survival trends. The study included 2402 patients, with a mean age of 69.3 years and a mean eGFR of 82.3 mL/min/1.73 m2. Short-term improvement rates were highest in stage 4 (24.4%) and stage 3 (16.8%) patients. Deterioration rates were highest in stage 1 (38.1%) and stage 2 (34.8%) patients. Deterioration in the chronic kidney disease stage was associated with a higher ten-year mortality (p < 0.001, HR 1.46); an improved stage trended toward improved survival (p = 0.14, HR 0.722). Patients with stage 3 and 4 kidney disease tended to remain stable or improve in the short term after aortic valve replacement while patients at stages 1 and 2 were at increased risk of deteriorating.

Risk of breakthrough COVID-19 after vaccination among people with multiple sclerosis on disease-modifying therapies.

BACKGROUND: Disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) may decrease vaccine effectiveness. We aimed to explore the association between various DMTs and the risk for breakthrough COVID-19. METHODS: Population-based data from Clalit Health Services, Israel's largest healthcare organization, were used. PwMS treated with DMTs without prior COVID-19 were followed from the commencement of the mass vaccination campaign in December 2020. The end of follow-up was at the time of COVID-19 infection, the receipt of a third vaccine dose or until the end of August 2021. Time-dependent multivariate Cox proportional hazard models were used to estimate hazard ratios for COVID-19 according to vaccination, DMT, age, gender, disability and comorbidities. RESULTS: 2511 PwMS treated with DMTs were included (Age: 46.2 ± 14.6, 70% Female, EDSS: 3.0 ± 2.1). Of whom, 2123 (84.5%) received 2 vaccine doses. On multivariate models that included all pwMS, vaccination was protective (HR = 0.41, P < 0.001). On multivariate models that included only fully vaccinated pwMS cladribine, ocrelizumab, S1P receptor modulators and natalizumab were associated with breakthrough COVID-19 (HR = 6.1, 4.7, 3.7 and 3.3; P = 0.004, 0.008, 0.02 and 0.05, respectively). On multivariate models that included unvaccinated and fully vaccinated pwMS on each DMT separately, a protective trend was noted for vaccination on all DMTs (0.09 < HR < 0.65), except for cladribine (HR = 1.1). This protective trend was not statistically significant on ocrelizumab, S1P receptor modulators and natalizumab. COVID-19 among pwMS was generally mild. Only 2 vaccinated pwMS had a severe infection with eventual recovery. CONCLUSIONS: Vaccination effectively protects pwMS from COVID-19. An increased risk of breakthrough infection was noted on high-efficacy DMTs, however COVID-19 after vaccination was usually mild.