Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline

Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the matrix degradation cascade associated with Achilles tendon rupture and disease. The goal of this study was to examine the effects of daily administration of doxycycline (Doxy) through oral gavage on MMP activity and on the repair quality of Achilles tendons in vivo. Our findings indicate that Achilles tendon transection resulted in increasing MMP‐8 activity from 2 to 6 weeks post‐injury, with peak increases in activity occurring at 4 weeks post‐injury. Doxy adiministration at clinically relevant serum concentrations was found to significantly inhibit MMP activity after continuous treatment for 4 weeks, but not for continuous administration for shorter durations (96 h or 2 weeks). Extended doxy administration was also associated with improved collagen fibril organization, and enhanced biomechanical properties (stiffness, ultimate tensile strength, maximum load to failure, and elastic toughness). Our findings indicate that a temporal delay exists between Achilles tendon transection and associated increases in MMP‐8 activity in situ. Our findings suggest that inhibition of MMP‐8 at its peak activity levels ameliorates fibrosis development and improves biomechanical properties of the Achilles tendon. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:500–506, 2014.     

Host perforin reduces tumor number but does not increase survival in oncogene-driven mammary adenocarcinoma

The concept of tumor immune surveillance has been supported by several recent studies in mice which show that immune effector mechanisms suppress hematologic malignancy. However, because the most common forms of human cancer are epithelial in origin, and comparatively very little data supports the immune surveillance of epithelial malignancies, we have chosen to evaluate the role of perforin-mediated cytotoxicity in the prevention of BALB/c Her2/neu-induced mammary cancer. Interestingly, perforin significantly delayed the onset of mammary tumorigenesis and reduced the number of mammary tumors without improving survival. Natural killer cell, but not CD8+ T cell, depletion resulted in a similar phenotype to perforin deficiency in this regard. Histologic analysis further indicated that the effect of perforin was most evident during the earliest stages of carcinogenesis rather than prior to or during the hyperplastic phase. This data suggests that perforin may mediate some suppression of epithelial carcinogenesis by intervening early in the tumor development process.     

Alpha-1 Antitrypsin Deficiency in Canada: Regional Disparities in Diagnosis and Management

Abstract

Background: Since 1999, as part of the Alpha1 International Registry (AIR), the Canadian Alpha-1 Antitrypsin Deficiency (AATD) Registry has maintained demographic and medical information volunteered by AATD individuals.

Methods: We undertook a retrospective chart review to describe the characteristics of registry participants. Inclusion criteria were ZZ phenotype or other severe deficiency and written consent. We reviewed baseline medical records and annual follow-ups, conducted by mail.

Results: The number of registrants ranged from 8.7 per million in British Columbia and Ontario to 1.3 per million in Quebec. Similarly, the rate of augmentation therapy use ranged from 7.7 per million in British Columbia to 0.1 per million in Quebec. 290 patients (146 males), most PiZZ, were enrolled by 2013. Patients with lung disease reported symptoms onset at (mean ± SD) 40 ± 11 years but were diagnosed as AATD at 47 ± 10 years. Typical patients were ex-smokers with respiratory symptoms, severely reduced FEV₁, an accelerated rate of FEV₁ decline, and minimal bronchodilator response. A subgroup diagnosed by liver disease or familial screening was younger and had better preserved lung function but a similar rate of FEV₁ decline. There were 63 deaths, of which 29 were lung-related and 6 were liver-related. Average age at death was 60.5 ± 11.2 years. 

Discussion: Most patients experience a diagnostic delay of seven years after symptom onset, a period during which lung health may deteriorate further. There is marked regional variation in the rate of diagnosis and specific therapy usage for AAT in Canada.     

Transitioning From Room to Zoom: The 2020 Cardiovascular Fellows’ Boot Camp in the COVID-19 Era

For 10 years, the annual Houston Methodist Cardiovascular Fellows’ Boot Camp hosted hundreds of cardiovascular trainees in Houston for a concise yet comprehensive 3-day training program for new fellows. The cornerstone of the program was the hands-on Skills Academy, which included a variety of timed learning stations that taught surgical techniques, dissection skills, and suturing techniques as well as echocardiography and cardiac catheterization using simulators. This was followed by 2 days of didactics covering essential topics in each specialty. However, that model was upended in 2020 by the COVID-19 pandemic. The pandemic forced the digitization of medical education and posed significant challenges as we transitioned Boot Camp to a virtual format. In this editorial, we review our experience designing and implementing a virtual cardiology track of the Houston Methodist Cardiovascular Fellows’ Boot Camp and highlight challenges and proposed solutions in the era of virtual education.     

A prospective randomized,controlled trial of eculizumab to prevent ischemia‐reperfusion injury in pediatric kidney transplantation

Ischemia‐reperfusion injury has multiple effects on a transplanted allograft, including delayed or impaired graft function, compromised long‐term survival, and an association with an increased incidence of rejection. Eculizumab, a monoclonal antibody blocking terminal complement activation, has been postulated to be an effective agent in the prevention or amelioration of IRI. We performed a single‐center prospective, randomized controlled trial involving 57 pediatric kidney transplant recipients between 2012 and 2016. The immunosuppressive protocol included two doses of alemtuzumab; half of the patients were randomized to receive a single dose of eculizumab prior to transplantation. Maintenance immunosuppression was based on a combination of low‐dose tacrolimus and mycophenolate, without steroids. Eculizumab‐treated patients had a significantly better early graft function, less arteriolar hyalinosis and chronic glomerulopathy on a protocol biopsies taken on day 30, 1 year, and 3 years after transplantation. In the eculizumab group, four non‐vaccinated children lost their grafts during the course of a flu‐like infection. Eculizumab is associated with better early graft function and improved graft morphology; however, there was an unacceptably high number of early graft losses among the eculizumab‐treated children. While a promising strategy, the best approach to complement inhibition remains to be established.     

Prevalence and correlates of COVID-19 vaccine hesitancy among the elderly in Qatar: A cross-sectional study

Older individuals are more vulnerable to severe coronavirus disease 2019 and medical complications. Vaccination stands as an efficient and safe vanguard against infection. However, negative attitudes and perceptions pertaining to available vaccines might hinder community inoculation. The aim of this study was to assess vaccine hesitancy and its psychosocial determinants among the elderly in Qatar.We conducted a cross-sectional study between October 15 and November 15, 2020, using a composite online survey including the Vaccine Attitudes Examination Scale in addition to questions on sociodemographic correlates and the role of healthcare professionals.The vaccine hesitancy rate was 19.5%. The main reasons for willingness to vaccinate included understanding the nature of disease and role of vaccination, in addition to information provided by physicians. Fears mainly centered around vaccine safety. Vaccine hesitators were more likely to be non-Qatari and having received the influenza vaccine at least once. Gender, marital status, socioeconomic status, educational level, and having completed childhood vaccinations were not associated with vaccine hesitancy.Efforts should be directed toward raising awareness of vaccine efficacy and safety profiles. Physicians should additionally be educated about their pivotal role in advocating vaccine acceptance. We recommend reassessing vaccine hesitancy and its associated factors following a year of campaigning and vaccine administration to identify and target vulnerable groups.