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Frexalimab, a second-generation anti-CD40L monoclonal antibody, demonstrated safety and efficacy in participants with relapsing multiple sclerosis (pwRMS) in the12-week (W) double-blind period of a phase 2 trial (NCT04879628), with an 89% reduction in new gadolinium-enhancing lesions in the high-dose group versusplacebo. This was accompanied by a 24% reduction in plasma neurofilament light (pNfL), a biomarker of neuroaxonal damage. Here, we describe changes in pNfL levelswith frexalimab treatment until W48. 129 pwRMS were randomized 4:4:1:1 to frexalimab-high, frexalimab-low, placebo-high, or placebo-low groups; participants receiving placebo switched to respective frexalimab groups at W12. Plasma samples were collected at baseline, W12, W24 and W48, and pNfL levels were measured using the Simoa® NF-LIGHT™ assay. Here, geometric means are reported at baseline and W48. A one-way ANOVA was used to examine differences in pNfL levels across treatment groups at baseline. Differences from baseline were calculated using percent change. 125/129 (97%) participants completed the double-blind period and entered the open-label extension. At baseline (n=123), pNfL levels (geometric mean [SD]) were similar across groups (F=0.09, p=0.97): 11.9 [2.0] in frexalimab-high, 12.7 [1.8] in frexalimab-low, 12.5 [1.9] in placebo-high/frexalimab-high, and 12.2 [1.8] pg/ml in placebo-low/frexalimab-low. At W48 (n=108), pNfL levels were reduced to 6.7 [2.0] in frexalimab-high, 8.1 [1.7] in frexalimab-low, 9.6 [1.7] in placebo-high/frexalimab-high, and 7.8 [2.1] pg/ml in placebo-low/frexalimab-low corresponding to a 41%, 35%, 24%, and 33% reduction from baseline, respectively. The observed reduction in pNfL through W48 provides evidence that frexalimab markedly reduces neuroaxonal damage in pwRMS. [ABSTRACT FROM AUTHOR]

Although the impact of poorly controlled diabetes on surgical outcomes of patients undergoing lower extremity revascularization is well-known, it is not clear if immediate postoperative hyperglycemia (IPH) itself can be used as a surrogate for poor outcomes after peripheral arterial bypass. We sought to examine the effect of IPH in this patient population with its impact on short-term and long-term outcomes. Retrospective review was completed for 505 patients who underwent either suprainguinal bypass surgery or infrainguinal bypass surgery between July 2002 and April 2018 for the treatment of peripheral arterial disease. All patients were undergoing first-time open bypass grafting. Patients were stratified into those who were normoglycemic or hyperglycemic (glucose ≥ 140 mg/dL) within 24 hours after surgery. A comparative analysis was performed on comorbidities and outcomes. Of 505 patients who underwent bypass grafting, 255 patients (50.5%) were hyperglycemic. The mean age of patients was 63.5 ± 14.1 years. The median follow-up was 5.2 years (range, 0.0-15.2 years). The distribution of procedures was as follows: femoral to popliteal bypasses (29%), femoral to femoral bypasses (17%), femoral to tibial bypasses (12%), aortobifemoral bypasses (10%), iliofemoral bypasses (9%), and axillofemoral bypasses (7%). At 30 days, hyperglycemic patients had an increased incidence of limb loss (8.3% vs 4.0%) and myocardial infarction (4.8% vs 0.8%) and incurred higher costs of hospital stay ($27,701 vs $22,990) (all P <.05). At 10 years, these patients had a higher incidence of needing major amputations (15.4% vs 9.4%; P =.025). Hyperglycemia after infrainguinal bypass was associated with nearly twice the risk of limb loss at 5 years (hazard ratio, 1.91; P =.034). Among the cohort of patients who required major amputations, the time duration between index revascularization and amputation was significantly shorter as compared with normoglycemic patients (P =.003). In this single-institution study with long-term follow-up, IPH was associated with increased rates of 30-day amputation and myocardial infarction, as well as an increased cost of hospital stay. In the long term, postoperative hyperglycemia was associated with greater major limb loss. Among the cohort of patients who required major amputations, the time period between revascularization and amputation was shorter for those patients who had IPH. IPH is an independent marker for poor outcomes after lower extremity revascularization procedures. [ABSTRACT FROM AUTHOR]

Summary: Background: Many studies have evaluated the effects of different interventions on hamstring length. However, little research has been conducted on the effects of deep stripping massage strokes (DSMS) alone, or combined with eccentric resistance, on hamstring length and strength. Purpose: To determine: 1) if DSMS have an effect on hamstring length and strength and 2) if the effects on hamstring length and strength are any different when DSMS are combined with eccentric exercise. Methods: 89 Community College students and community members between the ages of 18 and 62 volunteered for the study. Of these, 64 demonstrated tight hamstrings on either one or both sides as defined by supine, passive terminal knee extension of ≤75° and participated in the study. Strength was assessed by pressing the posterior calcaneus into a strain gauge for approximately 5 s while seated with the knee flexed to 90°. On their tighter side, participants were administered longitudinal DSMS during 15, 10-s bouts of eccentric resistance with an elastic resistance band. On their other hamstring, participants were administered 15, 10-s longitudinal DSMS while lying passive. All massage strokes were performed at a depth of 7 out of 10 on a verbal pressure scale index. Afterwards, the hamstring flexibility and strength tests were repeated. Results: Both DSMS with eccentric resistance (10.7%) and DSMS alone (6.3%) resulted in improved (p < 0.01) hamstring flexibility. The improvement following DSMS with eccentric resistance was greater (p < 0.05) than following DSMS alone. Strength was not significantly affected by either treatment. Conclusions: These results suggest that DSMS increases hamstring length in less than 3 min but has no affect on strength. Furthermore, combining DSMS with eccentric resistance produces more hamstring flexibility gains than DSMS alone and does not affect strength. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate and confirm efficacy and safety of electrochemotherapy with bleomycin or cisplatin on cutaneous and subcutaneous tumour nodules of patients with malignant melanoma and other malignancies in a multicenter study. Patients and methods: This was a two year long prospective non-randomised study on 41 patients evaluable for response to treatment and 61 evaluable for toxicity. Four cancer centers enrolled patients with progressive cutaneous and subcutaneous metastases of any histologically proven cancer. The skin lesions were treated by electrochemotherapy, using application of electric pulses to the tumours for increased bleomycin or cisplatin delivery into tumour cells. The treatment was performed using intravenous or intratumoural drug injection, followed by application of electric pulses generated by a Cliniporator™ using plate or needle electrodes. Tumour response to electrochemotherapy as well as possible side-effects with respect to the treatment approach, tumour histology and location of the tumour nodules and electrode type were evaluated. Results: An objective response rate of 85% (73.7% complete response rate) was achieved on the electrochemotherapy treated tumour nodules, regardless of tumour histology, and drug used or route of its administration. At 150 days after the treatment (median follow up was 133 days and range 60–380 days) local tumour control rate for electrochemotherapy was 88% with bleomycin given intravenously, 73% with bleomycin given intratumourally and 75% with cisplatin given intratumourally, demonstrating that all three approaches were similarly effective in local tumour treatment. Furthermore, electrochemotherapy was equally effective regardless of the tumour type and size of the nodules treated. Side-effects of electrochemotherapy were minor and acceptable, as reported by the patients. Conclusion: We demonstrated that electrochemotherapy is an easy, highly effective, safe and cost-effective approach for the treatment of cutaneous and subcutaneous tumour nodules of different malignancies. Electrochemotherapy can provide immediate clinical benefit in patients with advanced cutaneous and subcutaneous metastases. [Copyright &y& Elsevier]

Abstract: By short, intense electric pulses it is possible to cause cell permeabilisation (electroporation) and this can be used to deliver chemotherapy to tumours (electrochemotherapy). Preclinical studies have shown effects on vasculature of electroporation and electrochemotherapy, in particular in tumours. The effect on normal vasculature is a brief reflexory constriction; however in the fragile and abundant vasculature of tumours, a direct anti-vascular effect has been shown. This finding is mirrored in the clinical observation that bleeding, ulcerated lesions cease to bleed after application of electric pulses, and stay dry while the involution of tumours due to uptake of the cytotoxic agent takes place. Ulcerated, bleeding lesions are not uncommon in cancer patients, and cause discomfort due to bleeding and also stigmatisation when lesions are in visible areas. This report describes a case with ulcerated, bleeding lesions where the use of electrochemotherapy has led to efficient and immediate relief of symptoms. [Copyright &y& Elsevier]