Percutaneous coronary intervention of or through saphenous vein grafts or internal mammary arteries: the impact of stents, adjunctive pharmacology, and multicomponent distal protection.

We hypothesized that the use of stents and aggressive adjunctive pharmacotherapies has been associated with lower rates of complicating myocardial infarction (MI) and improved long-term outcomes compared to either previous balloon-only percutaneous coronary intervention (PCI) or atheroablative intervention for lesions of or through saphenous vein grafts (SVGs) and/or internal mammary arteries (IMAs). PCI of SVG has been complicated by relatively high rates of procedural MI and less favorable long-term outcomes than native vessel PCI, stimulating the development and application of an array of technologies. This study was based on retrospective review of stent-era (1999-2004) 5-year experience of a single center with 95 SVG procedures in 85 patients and 20 IMA procedures in 20 patients. These cases were compared with the previously published experience of one of the operators during the balloon-only period and literature review of the application of multiple technologies to SVG intervention, as well as consideration of the reoperation alternative. There was one in-hospital death each in the SVG cohort (1%) and in the IMA cohort (5%). There were SIX procedural MIs (6%), defined by total CK > normal, and 19 procedural MIs (20%) based on troponin-I > 1.0. Follow-up has been from 4 months to 5 years (average, 2.5 years), with 91% survival and one late CABG in the IMA group. SVG PCI with stents and adjunctive pharmacotherapies is associated with relatively low rates of procedural MI and favorable long-term outcomes.     

Purpura chez une jeune femme hyperthyroïdienne

IntroductionPropylthiouracil (PTU) is a synthetic antithyroid drug that can induce ANCA-associated vasculitis.ObservationA 27-year-old woman diagnosed with Graves’ disease was on PTU for the past 10 years. She developed purpuric lesions of the legs and on the tip of the nose diagnosed as vasculitis. ANCAs were positive, with anti-MPO and anti-PR3 on blood ELISA. After discontinuation of PTU, she was able to fully recover.ConclusionAll synthetic antithyroid drugs can induce ANCA-associated vasculitis, more often PTU. In most cases, antibodies are directed against MPO. Dual anti-MPO and anti-PR3 positivity is possible, but rare. The mechanism could be through an accumulation of PTU in neutrophils, altering the structure of MPO and making it immunogenic. PTU can also induce ANCA-free or lupus vasculitis, maculopapular rashes or urticaria. Many other drugs can induce ANCA-associated vasculitis.     

Lack of association of antihypertensive drugs with the risk and severity of COVID-19: A meta-analysis

BackgroundThe association of antihypertensive drugs with the risk and severity of COVID-19 remains unknown.Methods and ResultsWe systematically searched PubMed, MEDLINE, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and medRxiv for publications before July 13, 2020. Cohort studies and case-control studies that contain information on the association of antihypertensive agents including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium-channel blockers (CCBs), β-blockers, and diuretics with the risk and severity of COVID-19 were selected. The random or fixed-effects models were used to pool the odds ratio (OR) with 95% confidence interval (CI) for the outcomes.The literature search yielded 53 studies that satisfied our inclusion criteria, which comprised 39 cohort studies and 14 case-control studies. These studies included a total of 2,100,587 participants. We observed no association between prior usage of antihypertensive medications including ACEIs/ARBs, CCBs, β-blockers, or diuretics and the risk and severity of COVID-19. Additionally, when only hypertensive patients were included, the severity and mortality were lower with prior usage of ACEIs/ARBs (overall OR of 0.81, 95% CI 0.66?0.99, p < 0.05 and overall OR of 0.77, 95% CI 0.66?0.91, p < 0.01).ConclusionsTaken together, usage of antihypertensive drugs is not associated with the risk and severity of COVID-19. Based on the current available literature, it is not recommended to abstain from the usage of these drugs in COVID-19 patients.RegistrationThe meta-analysis was registered on OSF (https://osf.io/ynd5g).     

Glucocorticoid and mineralocorticoid cross-talk with progesterone receptor to induce focal adhesion and growth inhibition in breast cancer cells

Progesterone receptor (PR), glucocorticoid receptor, and mineralocorticoid receptor belong to a subfamily of nuclear receptor superfamily with similar sequence and structural characteristics. Many reports have documented glucocorticoid-like effects of progesterone in various tissues. This study addresses the issue of cross-talk between corticosteroids and PR using PR-transfected MDA-MB-231 cells ABC28 and vector-transfected control cells CTC15. At physiological concentrations, dexamethasone, cortisol, and aldosterone mimic the effects of progesterone by inducing significant growth inhibition, cell spreading, and focal adhesions in PR-positive ABC28 cells. These hormones also induce progesterone-like effects in increasing the expression of p21(CIP1/WAF1) protein and decreasing the level of phospho-p42/p44 mAPK. Two lines of evidence suggest that these effects are mediated by cross-talk with PR. First, these compounds do not exhibit the same progesterone-like effects in PR-negative CTC15 cells. Second, PR blocker ZK98299 abolishes their effect on cell spreading and focal adhesion in ABC28 cells. The cross-talk is corticosteroid specific because estradiol and thyroid hormone triiodothyronine have no effect on PR-transfected cells ABC28. It is also interesting to note that dexamethasone induces a small but detectable increase of focal adhesions and limited growth stimulation in vector-transfected cells CTC15. In contrast, progesterone exhibits no detectable effect on CTC15 cells. This study provides evidence that glucocorticoid and mineralocorticoid cross-talk with PR to produce progesterone-like effects in breast cancer cells. Glucocorticoid receptor and PR share some overlapping activity in mediating focal adhesion but not in regulating cell proliferation.     

Medical doctors’ knowledge of dental trauma management: A review

Education in dental trauma is extremely important to promote knowledge on the assessment and management of a traumatized tooth. Medical doctors are normally only required to manage the emergency phase of traumatic dental injury (TDI) treatment before referring to a dentist, endodontist or oral and maxillofacial surgeon for continuing care. Medical doctors who possess sufficient theoretical knowledge and are competent enough clinically to handle TDI can provide a higher standard of treatment care and ultimately achieve a better patient outcome. The aim of this literature review was to assess the extent of medical doctors’ knowledge of dental trauma management for injuries in the following four areas: (a) tooth structure; (b) to the supporting bone; (c) to the periodontal tissues; and (d) to the soft tissues. Based on the findings from this literature review, an overall deficiency in knowledge and confidence in managing dental trauma has been identified. Knowledge and understanding to categorize TDI using the same classification of dental injuries commonly used amongst dentists would allow medical doctors to better manage and communicate with dental colleagues concerning referral for further care. If the medical education curriculum provided medical doctors with more information and skills for the management of dental trauma and an understanding of the importance of early management, then more favourable outcomes may prevail for dental trauma patients.     

Physical proximity and functional interplay of PECAM-1 with the Fc receptor Fc gamma RIIa on the platelet plasma membrane

We and others have recently defined that Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1/CD31) functions as a negative regulator of platelet-collagen interactions involving the glycoprotein VI/Fc receptor gamma chain (GPVI/FcR-gamma chain) signaling pathway.1,2 In this study, we hypothesized that PECAM-1 may be physically and functionally associated with Fc gamma RIIa on the platelet membrane. The functional relationship between PECAM-1 and Fc gamma RIIa was assessed by determining the effect of anti-PECAM-1 monoclonal antibody Fab fragments on Fc gamma RIIa-mediated platelet aggregation and heparin-induced thrombocytopenia (HITS)-mediated platelet aggregation. Preincubation of washed platelets with monoclonal antibody fragments of 2BD4 directed against PECAM-1 and IV.3 directed against Fc gamma RIIa completely blocked Fc gamma RIIa-mediated platelet aggregation and HITS-mediated platelet aggregation, whereas anti-CD151 antibody had no blocking effect. Coengagement of Fc gamma RIIa and PECAM-1 resulted in negative regulation of Fc gamma RIIa-mediated phospholipase C gamma 2 activation, calcium mobilization, and phosphoinositide 3-kinase-dependent signaling pathways. In addition, the physical proximity of Fc gamma RIIa and PECAM-1 was confirmed by using fluorescence resonance energy transfer and coimmunoprecipitation studies. These results indicate that PECAM-1 and Fc gamma RIIa are colocalized on the platelet membrane and PECAM-1 down-regulates Fc gamma RIIa-mediated platelet responses.     

Bisphosphonate-associated peri-implant fractures: a new clinical entity?: A series of 10 patients with 11 fractures

Background and purpose

The current definition of atypical femoral fractures (AFFs) associated with bisphosphonate use includes only de novo fractures. However, in recent years reports of bisphosphonate-associated periprosthetic fractures involving stemmed arthroplasty implants have emerged. In a case series of peri-implant fractures in femurs with plate/screw constructs, we aimed to assess similarities with classical AFFs and how their location may have implications for the pathogenesis and management of AFFs.

Patients and methods

We retrospectively identified 10 patients with 11 peri-implant fractures.

Results

The patients were ambulant women, mean age 80 (70–92) years. Mean duration of bisphosphonate use was 5 (1–10) years. The peri-implant fractures were sustained an average of 4 years (6 months to 9 years) from the time of index surgery. They were all associated with low-energy mechanisms. 8 fractures occurred near the tip of a plate, while 3 traversed the penultimate screwhole of a plate. The peri-implant fractures showed clinical and radiological features of atypicality such as lateral cortical thickening, simple fracture pattern, and lack of comminution. The patients underwent revision surgery, with bone grafting used in all but 1 case. Radiological union was evident after 2–4 months.

Interpretation

Atypical peri-implant fractures of the femur associated with bisphosphonate use may be a new entity. Stress lesions and atypical fractures may tend to develop over stress risers along the operated femur. This finding has implications for the pathogenesis and clinical management of AFFs.Bisphosphonates form the cornerstone of antiresorptive therapy in the management of post-menopausal osteoporosis. They are used in the treatment of malignant and osteoclast-mediated metabolic bone disease. Their use in patients who have undergone total joint arthroplasty of the lower limb is associated with higher periprosthetic bone mineral density and longer implant survival (Bhandari et al. 2005). Bisphosphonates exert their therapeutic effect by reducing bone turnover and increasing overall mineralization. This translates to increased bone mineral density and bone strength, corresponding clinically to reduced risk of vertebral and non-vertebral fragility fractures (Black et al. 1996).In recent years, several published reports have described atypical femoral fractures (AFFs) of the proximal femoral diaphysis and subtrochanteric region, in association with bisphosphonate use (Goh et al. 2007, Neviaser et al. 2008, Isaacs et al. 2010). Bisphosphonates are associated with a higher age-adjusted relative risk of AFF in women than in men, which is higher in alendronate users than in risedronate users (Schilcher et al. 2015). Bisphosphonates may cause changes in bone matrix composition and bone mechanical properties, increasing the propensity for accumulation of microdamage. Impaired target remodeling would contribute to the progression of macrocracks. High interfragmentary strain from physiological loads at a thin fracture line may be a mechanical factor in lack of bone healing (Aspenberg et al. 2010).Periprosthetic/peri-implant fractures are currently excluded from the definition of AFFs. We suggest that peri-implant fractures of the femur with features of atypicality may be linked to bisphosphonate use and that they should be recognized as a clinical entity.     

Advances in the management of diabetic macular oedema based on evidence from the Diabetic Retinopathy Clinical Research Network

The Diabetic Retinopathy Clinical Research Network (DRCR.net) performs studies on new treatments for diabetic retinopathy. This review aims to summarise recent findings from DRCR.net studies on the treatment of diabetic macular oedema. We performed a PubMed search of articles from the DRCR.net, which included all studies pertaining to the treatment of diabetic maculopathy. The main outcome measures were retinal thickening as assessed by central subfield thickness on optical coherence tomography and improvement of visual acuity on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Findings from each study were divided into modalities of treatment, namely photocoagulation, bevacizumab, triamcinolone, ranibizumab and vitrectomy. While modified ETDRS focal/grid laser remains the standard of care, intravitreal corticosteroids or anti-vascular endothelial growth factor agents have also proven to be effective, although they come with associated side effects. The choice of treatment modality for diabetic macular oedema is a clinical judgement call, and depends on the patient’s clinical history and assessment.