Showing papers by "Jewish Hospital published in 2017"

Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment

Abstract: Background Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization, or to inhaled corticosteroid treatment. Objectives We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma. Methods Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2–related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment. Results The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus , Neisseria , Fusobacterium , and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2–high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. Conclusion Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.

Antimicrobial Resistant Streptococcus pneumoniae: Prevalence, Mechanisms, and Clinical Implications

Abstract: Background:Streptococcus pneumoniae is a major cause of pneumonia, meningitis, sepsis, bacteremia, and otitis media. S. pneumoniae has developed increased resistance to multiple classes of antibiotics.Study Design:Systematic literature review of prevalence, mechanisms, and clinical implications in S

Low-Dose Paclitaxel-Coated Versus Uncoated Percutaneous Transluminal Balloon Angioplasty for Femoropopliteal Peripheral Artery Disease: One-Year Results of the ILLUMENATE European Randomized Clinical Trial (Randomized Trial of a Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon).

Abstract: Background: Numerous studies have reported favorable outcomes using drug-coated balloons (DCBs) for treatment of symptomatic peripheral artery disease of the superficial femoral and popliteal arteries. However, the treatment effect compared with an uncoated balloon has differed greatly among the randomized trials, with better outcomes observed with higher-dose DCBs. This European trial was designed to assess the safety and effectiveness of a next-generation low-dose (2-µg/mm 2 surface dose of paclitaxel) DCB. Methods: This was a prospective, randomized, multicenter, single-blinded trial. Patients were randomized (3:1) to treatment with a low-dose DCB or an uncoated percutaneous transluminal angioplasty (PTA) balloon. The primary safety end point was a composite of freedom from device- and procedure-related death through 30 days after the procedure and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months after the procedure. The primary effectiveness end point was primary patency at 12 months. Results: Patients were randomized to treatment with a DCB (222 patients, 254 lesions) or uncoated PTA balloon (72 patients, 79 lesions) after successful predilatation. Mean lesion length was 7.2 and 7.1 cm, and 19.2% and 19.0% of lesions represented total occlusions, respectively. The primary safety end point was met, and superiority was demonstrated; freedom from a primary safety event was 94.1% (193 of 205) with DCB and 83.3% (50 of 60) with PTA, for a difference of 10.8% (95% confidence interval, 0.9%–23.0%). The primary effectiveness end point was met, and superiority of DCB over PTA was achieved (83.9% [188 of 224] versus 60.6% [40 of 66]; P P P =0.014). Conclusions: Superiority with a low-dose DCB for femoropopliteal interventions was demonstrated over PTA for both the safety and effectiveness end points. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01858363.

Factors associated with epinephrine administration for anaphylaxis in children before arrival to the emergency department

Abstract: Background Epinephrine is the first-line treatment for anaphylaxis but may be underused by patients and medical personnel. Objective To evaluate factors associated with anaphylaxis management before arrival at the emergency department (ED) or urgent care center (UCC). Methods We performed a retrospective review of electronic medical records for all patients aged 0 to 25 years presenting with anaphylaxis to the ED or UCC at a pediatric academic referral center during 2009 to 2013. Results A total of 408 patients (mean age, 7.25 years; 62% male) were included for analysis. Only 148 patients (36.3%) received epinephrine before arrival at the ED or UCC. Reactions occurring at home (n = 36/114) were less likely to be treated with epinephrine compared with reactions occurring at school (n = 30/49) (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.15–0.59). The odds of receiving epinephrine before arrival at the ED or UCC were significantly lower with a 2-organ system (OR, 0.50; 95% CI, 0.30–0.85) or 3-organ system (OR, 0.41; 95% CI, 0.21–0.81) presentation compared with 1-organ system involvement. Foods (342 [83.8%]) were the most commonly reported provoking trigger. Patients who did not receive epinephrine before arrival at the ED or UCC were significantly less likely to be discharged to home (OR, 0.56; 95% CI, 0.37–0.86; P = .01). Conclusion This study identifies factors associated with prehospital management of anaphylaxis for children, which highlight that epinephrine administration may be occurring with considerable delay. Increased awareness and education of caregivers, patients, and medical professionals are necessary to provide optimal management.

Peripheral Nerve Schwannoma: A Review of Varying Clinical Presentations and Imaging Findings

Abstract: A schwannoma or neurilemmoma is a benign, isolated, noninvasive, and encapsulated tumor originating from Schwann cells of the peripheral nerve sheath. The incidence of a schwannoma occurring in the foot and ankle is rare, with prevalence rate of 1% to 10%. Schwannomas have no sex predilection, and they commonly occur in patients in their fourth decade. Malignant transformation of benign schwannoma is unusual; however, it is important to note that malignant variants of schwannomas do exist and account for about 5% to 10% of all soft tissue sarcomas. We present 3 cases of benign schwannoma in the lower extremity. All 3 patients presented with varying clinical symptoms, including pain, paresthesia, weakness, and a palpable mass. A schwannoma was eventually diagnosed in all 3 patients. We discuss and review the known entities of peripheral nerve schwannoma and describe the clinical and imaging findings and therapeutic strategies for treating and diagnosing peripheral nerve schwannoma.

Do Stem Taper Microgrooves Influence Taper Corrosion in Total Hip Arthroplasty? A Matched Cohort Retrieval Study

Abstract: Background Previous studies identified imprinting of the stem morphology onto the interior head bore, leading researchers to hypothesize an influence of taper topography on mechanically assisted crevice corrosion. The purpose of this study was to analyze whether microgrooved stem tapers result in greater fretting corrosion damage than smooth stem tapers. Methods A matched cohort of 120 retrieved head-stem pairs from metal-on-polyethylene bearings was created controlling for implantation time, flexural rigidity, apparent length of engagement, and head size. There were 2 groups of 60 heads each, mated with either smooth or microgrooved stem tapers. A high-precision roundness machine was used to measure and categorize the surface morphology. Fretting corrosion damage at the head-neck junction was characterized using the Higgs-Goldberg scoring method. Fourteen of the most damaged heads were analyzed for the maximum depth of material loss and focused ion beam cross-sectioned to view oxide and base metal. Results Fretting corrosion damage was not different between the 2 cohorts at the femoral head ( P = .14, Mann-Whitney) or stem tapers ( P = .35). There was no difference in the maximum depths of material loss between the cohorts ( P = .71). Cross-sectioning revealed contact damage, signs of micro-motion, and chromium-rich oxide layers in both cohorts. Microgroove imprinting did not appear to have a different effect on the fretting corrosion behavior. Conclusion The results of this matched cohort retrieval study do not support the hypothesis that taper surfaces with microgrooved stems exhibit increased in vivo fretting corrosion damage or material release.

Electrocardiographic assessments and cardiac events after fingolimod first dose – a comprehensive monitoring study

Abstract: Background First dose observation for cardiac effects is required for fingolimod, but recommendations on the extent vary. This study aims to assess cardiac safety of fingolimod first dose. Individual bradyarrhythmic episodes were evaluated to assess the relevance of continuous electrocardiogram (ECG) monitoring. Methods START is an ongoing open-label, multi-center study. At the time of analysis 3951 patients were enrolled. The primary endpoints are the incidence of bradycardia (heart rate Results Thirty-one patients (0.8%) developed bradycardia ( Conclusions Continuous Holter ECG monitoring in this large real-life cohort revealed that bradycardia and AV conduction abnormalities were rare, transient and benign. No further unexpected abnormalities were detected. The data presented here give an indication that continuous Holter ECG monitoring does not add clinically relevant value to patients’ safety. Trial registration NCT01585298 ; registered April 23, 2012.

Predicting Inpatient Detoxification Outcome of Alcohol and Drug Dependent Patients: The Influence of Sociodemographic Environment, Motivation, Impulsivity, and Medical Comorbidities.

Abstract: Aims. This prospective study aims to identify patient characteristics as predictors for treatment outcome during inpatient detoxification treatment for drug and alcohol dependent patients. Methods. A mixed gender sample of 832 consecutively admitted drug and alcohol dependent patients were interviewed by an experienced physician. The impact of a variety of factors concerning social environment, therapy motivation, impulsivity related variables, medical history, and addiction severity on treatment outcome was examined. Results. 525 (63.1%) of the patients completed detoxification treatment whereas 307 (36.9%) dropped out prematurely. Being female, living in a partnership, having children, being employed, and having good education were predictive for a positive outcome. Family, health, the fear of losing the job, prosecution, and emergency admission were significant motivational predictors for treatment outcome. Being younger, history of imprisonment, and the number of previous drop-outs were predictive for a negative outcome. Conclusions. Variables concerning social environment and the number of previous drop-outs have been identified as best predictors for treatment outcome. Socially stable patients benefit from the current treatment setting and treatment shall be adapted for patients with negative predictors. Treatment may consequently be tailored with respect to intervention type, duration, and intensity to improve the outcome for those patients that fulfil criteria with negative impact on treatment retention.

Oxidation, Damage Mechanisms, and Reasons for Revision of Sequentially Annealed Highly Crosslinked Polyethylene in Total Knee Arthroplasty

Abstract: Background Sequentially annealed, highly crosslinked polyethylene (HXLPE) has been used clinically in total knee arthroplasty (TKA) for over a decade However, little is known about the revision reasons; its surface damage mechanisms; or its in vivo oxidative stability relative to conventional polyethylene We asked whether retrieved HLXPE tibial inserts exhibited: (1) similar revision reasons; (2) improved resistance to surface damage; and (3) improved oxidative stability, when compared with conventional gamma inert sterilized polyethylene inserts Methods A total of 456 revised tibial inserts were collected in a multicenter retrieval program between 2000 and 2016 The implantation time for the HXLPE components was 18 ± 18 years, and for the control inserts it was 34 ± 27 years Revision reasons were assessed based on medical records, radiographs, and examinations of the retrieved components Surface damage was assessed using a semi-quantitative scoring method Oxidation was measured using Fourier transform infrared spectroscopy Results The tibial inserts in both cohorts were revised most frequently for loosening, infection, and instability The most commonly observed surface damage modes were burnishing, pitting, and scratching Oxidation of the HXLPE inserts was, on average, low and similar to the control inserts at the bearing surface and the stabilizing post Conclusions We observed evidence of in vivo oxidation in both HXLPE and control tibial inserts We found no association between the levels of oxidation and the clinical performance of the HXLPE tibial components The findings of this study document the revision reasons, surface damage modes, and oxidative behavior of sequentially annealed HXLPE for TKA

Thrombophilia in Klinefelter Syndrome With Deep Venous Thrombosis, Pulmonary Embolism, and Mesenteric Artery Thrombosis on Testosterone Therapy: A Pilot Study:

Abstract: We compared thrombophilia and hypofibrinolysis in 6 men with Klinefelter syndrome (KS), without previously known familial thrombophilia, who had sustained deep venous thrombosis (DVT)–pulmonary emboli (PE) or mesenteric artery thrombosis on testosterone replacement therapy (TRT). After the diagnosis of KS, TRT had been started in the 6 men at ages 11, 12, 13, 13, 19, and 48 years. After starting TRT, DVT-PE or mesenteric artery thrombosis was developed in 6 months, 1, 11, 11, 12, and 49 years. Of the 6 men, 4 had high (>150%) factor VIII (177%, 192%, 263%, and 293%), 3 had high (>150%) factor XI (165%, 181%, and 193%), 1 was heterozygous for the factor V Leiden mutation, and 1 was heterozygous for the G20210A prothrombin gene mutation. None of the 6 men had a precipitating event before their DVT-PE. We speculate that the previously known increased rate of DVT-PE and other thrombi in KS reflects an interaction between prothrombotic, long-term TRT with previously undiagnosed familial thrombophilia. Thrombop...

Platelet Count and Mean Platelet Volume at the Time of and After Acute Myocardial Infarction.

Abstract: Platelet count has been shown to be lower and mean platelet volume (MPV) to be higher in acute myocardial infarction (MI). However, it is not known whether these changes persist post-MI or if these measures are able to distinguish between acute thrombotic and non-thrombotic MI. Platelet count and MPV were measured in 80 subjects with acute MI (thrombotic and non-thrombotic) and stable coronary artery disease (CAD) at cardiac catheterization (acute phase) and at >3-month follow-up (quiescent phase). Subjects were stratified using stringent clinical, biochemical, histological, and angiographic criteria. Outcome measures were compared between groups by analysis of variance. Forty-seven subjects met criteria for acute MI with clearly defined thrombotic (n = 22) and non-thrombotic (n = 12) subsets. Fourteen subjects met criteria for stable CAD. No significant difference was observed in platelet count between subjects with acute MI and stable CAD at the acute or quiescent phase. MPV was higher in acute MI (9.18 ± 1.21) compared to stable CAD (8.13 ± 0.66; P = 0.003) at the acute phase but not at the quiescent phase (8.48 ± 0.58 vs 8.94 ± 1.42; P = 0.19). No difference in platelet count or MPV was detected between thrombotic and non-thrombotic subsets at acute or quiescent phases. The power to detect differences in these measures between thrombotic and non-thrombotic subsets was 58%. Higher MPV at the time of acute MI is not observed by 3 months post-MI (quiescent phase). Platelet count and MPV do not differ in subjects with thrombotic versus non-thrombotic MI. Further investigation is warranted to evaluate the utility of these measures in the diagnosis of acute MI.

Efficacy, safety, Low density lipoprotein cholesterol lowering, and calculated 10-year cardiovascular risk reduction of alirocumab and evolocumab in addition to maximal tolerated cholesterol lowering therapy: a post-commercialization study

Abstract: Efficacy and safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO) have previously been evaluated through controlled clinical trials with selective patient groups. Post-commercially, in patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated cholesterol lowering therapy, we assessed efficacy and safety of ALI and EVO. Post-commercially, we started 25 patients on ALI 75 mg, 15 on ALI 150 mg, and 32 on EVO 140 mg bi-weekly added to entry LDLC lowering regimen, with follow-up for a median 24 weeks. History, physical exam, demographics, and adverse event data were collected. Changes in LDLC and AHA and NIH calculated 10-year CVD risks were assessed on ALI and EVO. Of 72 patients, 25 had HeFH only, 25 CVD only, 22 had both, median age was 65 years, 63% females, 38% males, 86% Caucasian, 11% African-Americans, 17% diabetics, 63% on anti-hypertensives, and 7% smokers. At entry, 30 (42%) were on a statin and 42 (58%) could not tolerate any statins. At 24-weeks, median LDLC decreased on ALI 75 mg from 117 to 62 mg/dL (−54%), on ALI 150 mg from 175 to 57 mg/dL (−63%), and on EVO 140 mg from 165 to 69 mg/dL (−63%), p .05) between ALI 150 and EVO 140 mg, but were less on ALI 75 mg vs ALI 150 mg and EVO 140 mg (p <.05). Percent reductions in 10-year CVD risks by AHA and NIH calculators, respectively were ALI 75 mg −22 and −44%, ALI 150 mg −31 and −50%, and EVO 140 mg −29 and −56%, p ≤.002 for all. The three most common adverse events included flu-like myositis 10%, respiratory tract symptoms 8%, and injection site reaction 6%. In patients with HeFH and/or CVD, LDLC was lowered by 63% on EVO and ALI 150 mg, and 54% on ALI 75 mg. Adverse events were minimal and tolerable. ALI and EVO represent paradigm shifts in LDLC lowering. Long term, post-commercial safety and efficacy remain to be determined.

Case report: primary osteonecrosis associated with thrombophilia-hypofibrinolysis and worsened by testosterone therapy

Abstract: Familial and acquired thrombophilia are often etiologic for idiopathic hip and jaw osteonecrosis (ON), and testosterone therapy (TT) can interact with thrombophilia, worsening ON. Case 1: A 62-year-old Caucasian male (previous deep venous thrombosis), on warfarin 1 year for atrial fibrillation (AF), had non-specific right hip-abdominal pain for 2 years. CT scan revealed bilateral femoral head ON without collapse. Coagulation studies revealed Factor V Leiden (FVL) heterozygosity, 4G/4G plasminogen activator inhibitor (PAI) homozygosity, high anti-cardiolipin (ACLA) IgM antibodies, and endothelial nitric oxide (NO) synthase (eNOS) T786C homozygosity (reduced conversion of L-arginine to NO, required for bone health). Apixaban 5 mg twice daily was substituted for warfarin; and L-arginine 9 g/day was started to increase NO. On Apixaban for 8 months, he became asymptomatic. Case 2: A 32-year-old hypogonadal Caucasian male had 10 years of unexplained tooth loss, progressing to primary jaw ON with cavitation 8 months after starting TT gel 50 mg/day. Coagulation studies revealed FVL heterozygosity, PAI 4G/4G homozygosity, and the lupus anticoagulant. TT was discontinued. Jaw pain was sharply reduced within 2 months. Idiopathic ON, often caused by thrombophilia-hypofibrinolysis, is worsened by TT, and its progression may be slowed or stopped by discontinuation of TT and, thereafter, anticoagulation. Recognition of thrombophilia-hypofibrinolysis before joint collapse facilitates anticoagulation which may stop ON, preserving joints.

Real-world experience with a Paclitaxel-Coated Balloon for the treatment of atherosclerotic infrainguinal arteries: 12-month interim results of the BIOLUX P-III registry first year of enrolment.

Abstract: Background Endovascular management of atherosclerotic infrainguinal arteries recently shifted towards drug eluting devices, designed to locally prevent the restenosis process. Numerous clinical studies report an advantage of drug coated balloons over uncoated balloon angioplasty in treating lower extremity peripheral artery disease. However, as coating and balloon platforms are different, each device requires dedicated clinical evaluations. Objective The aim of the study is to further investigate the safety and effectiveness of a Paclitaxel-Coated Balloon for the treatment of atherosclerotic infrainguinal arteries in a real-world setting. Methods 203 patients out of a final sample of 882 were enrolled in this prospective multicenter, observational, all-comers registry during the first 12 months. The primary endpoints were major adverse events (defined as procedure or device related death within 30 days post index procedure, clinically-driven target lesion revascularization or major target limb amputation) at 6 months and freedom from clinically-driven target lesion revascularization at 12 months. Both endpoints were adjudicated by a Clinical Events Committee. Results Mean patient age was 70.2±10.4 years (60.1% male). 47.3% of the patients were diabetic and 67.5% had a history of smoking. Severe claudication was reported in 37.4% and 40% had critical limb ischemia. 257 lesions, including 13.2% in the infrapopliteal territory, were treated with Passeo-18 Lux (mean lesion length 75.1 mm±69.4, 20% occlusions, 76.3% calcified). At 6 months, the rate of major adverse events was 5.5% (95%CI 3.1-9.7). Freedom from clinically-driven target lesion revascularization at 12 months was 93.2% (95%CI 89.1-95.8). All causes mortality was 6.5% (95%CI 3.8-11.0) and overall amputation rate was 4.2% (95%CI 2.1-8.3) at 12 months. Conclusion In a real-world environment, the BIOLUX P-III registry preliminary results confirm the safety and efficacy of the Paclitaxel-Coated Passeo-18 Lux balloon as a stand-alone treatment option for atherosclerotic infrainguinal arteries.

Wide Variability in Prethrombectomy Workflow Practices in the United States: A Multicenter Survey.

Abstract: BACKGROUND AND PURPOSE: Clinical outcomes in patients with acute ischemic stroke caused by large vessel occlusion depend on the speed and quality of workflows leading to mechanical thrombectomy. In the absence of universally accepted best practices for workflow, developing stroke hospitals can benefit from improved awareness of real-world workflows in effect at experienced centers. To this end, we surveyed prethrombectomy workflow practices at stroke centers throughout the United States. MATERIALS AND METHODS: E-mail and phone interviews were conducted with neurointerventional team members at 30 experienced, endovascular-capable stroke centers. Questions were chosen to reflect workflow components of triage, team activation, transport, case setup, and anesthesia. RESULTS: There is wide variation in prethrombectomy workflows. At 53% of institutions, nonphysician staff respond to stroke alerts alongside physicians. Imaging triage involves noninvasive angiography or perfusion imaging at 97% and 63% of institutions, respectively. Neurointerventional consultation is initiated before the completion of neuroimaging at 86% of institutions, and the team is activated before a final treatment decision at 59%. The neurointerventional team most commonly arrives within 30 minutes. Patients may be transported to the neuroangiography suite before team arrival at 43% of institutions. Procedural trays are set up in advance of team arrival at 13% of centers; additional thrombectomy devices are centrally stored at 54%. A power injector for angiographic runs is consistently used at 43% of institutions. Anesthesiology routinely supports thrombectomies at 67% of institutions. CONCLUSIONS: Prethrombectomy workflows vary widely between experienced centers. Improved awareness of real-world workflows and their variations may help to guide institutions in designing their own protocols of care.

Efficacy and safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab and evolocumab, a post-commercialization study

Abstract: Efficacy-safety of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, alirocumab (ALI) and evolocumab (EVO), have previously been evaluated through controlled clinical trials with selective patient groups. Post-commercially, in 69 patients with heterozygous familial hypercholesterolemia (HeFH) and/or cardiovascular disease (CVD) with suboptimal LDL cholesterol (LDLC) lowering on maximal tolerated LDLC therapy, we assessed efficacy and safety of ALI and EVO. Post-commercially, we started 29 patients on ALI 75 mg, 18 on ALI 150 mg, and 22 on EVO 140 mg every 2 weeks added to a maximally tolerated LDLC-lowering regimen. Since LDLC lowering did not differ between ALI 150 and EVO 140 mg, ALI 150-EVO 140 data were pooled (ALI-EVO). Changes in LDLC and AHA and NIH calculated 10-year CVD risks were assessed. Of the 69 patients, 25 had HeFH, 25 CVD, and 19 had both. At entry, 23 (33%) took statins and 46 (67%) were statin-intolerant. Mean ± SD and median follow-up were 49 ± 13 and 49 weeks on ALI 75 mg, and 37 ± 12 and 33 weeks on ALI-EVO. In the ALI-EVO group (n = 40), median LDLC fell from 165 mg/dl at entry to 70 mg/dl (median − 59%, p 0.05) between ALI 75 mg and ALI-EVO. In patients with HeFH and/or CVD, LDLC decreased from 115 to 68 mg/dl (39%) on ALI 75 mg with mean follow-up of 49 weeks, and from 165 to 70 mg/dl (59%) on ALI-EVO over 37 weeks, p < .0001 for both. Adverse events were minimal and tolerable. ALI and EVO represent paradigm shifts in LDLC lowering.

The Dorsoulnar Artery Perforator Adipofascial Flap in the Treatment of Distal Radioulnar Synostosis.

Abstract: Posttraumatic radioulnar synostosis (RUS) is a rare event following forearm fractures. Consequences are disabling for patients who suffer from functional limitation in forearm pronosupination. Distal RUS are even more rare and more difficult to treat because of high recurrence rates. The patient we describe in this paper came to our attention with a double distal RUS recurrence and a Darrach procedure already performed. We performed a radical excision of RUS and interposition with a vascularized dorsoulnar artery (DUA) adipofascial perforator flap. Four years after surgery, the patient shows the same complete range of motion in pronosupination, and MRI confirms that the flap is still in place with signs of vascularization. Simple synostosis excision has been proven ineffective in many cases. Interposition is recommended after excision, and biological material interposition seems to be more effective than foreign material. Surgeons are increasingly performing vascularized interposition, and the results are very encouraging.

Suggestions to Increase the Number of African-American Male Physicians.

Abstract: “Are you here to transport her for the computedtomography scan?” The moment an African-American physician is plagued with this question they may concurrently feel insulted, embarrassed, and disappointed. Unfortunately, this will likely not be the first or the last time they will be questioned about their role when entering the room of a patient. At some point as anAfrican-Americanmale physician, one grows immune to the countless questions about their role and realizes they are a rarity. According to a report by the Association of American Medical Colleges (AAMC), the number of African-American men who applied to medical school between 1978 and 2014 has slightly decreased. Of a total of 26,445 men who applied in 2014, only 1,337 were African-American, which is 73 less than applied in 1978. The sheer numbers are an indication that the disparity must be addressed, but the important question is, “How?” To attract more African-American men into medicine, we have to address factors preventing their application to medical school. In 2007, Rao and Flores discovered that high school juniors reported that “financial constraints, insufficient exposure to medicine as a career, little encouragement at home and in schools, lack of role models, and negative peer pressuremay contribute to racial disparities in the physician workforce for African-Americans.” In addition, differences in education based on socioeconomic status, poor advice, bias/stereotypes against African-American men and difficulty with preparedness for a rigorous premedical curriculum are other barriers affecting both the quantity and quality of applications. Combating these multifaceted issues will require that we first expose younger students to African-American physicians as positive role models, increase scholarship opportunities to lessen financial barriers, and develop premed or science clubs to steer these students into math and science programs. As stated by Rao and Flores, a substantial number of African-Americans do not understand the pathway to becoming a physician. This is likely because many do not know any physicians personally other than their primary care provider, whom they may not see on a regular basis. Contributing to the lack of understanding is very likely the lack of African-American role models in the community. Many African-American physicians are not returning to underserved communities to give back. Without seeing or being exposed to African-American physicians, younger children may not believe they too can become physicians which can hinder their desire to apply to medical school. Financial constraints also limit entrance of AfricanAmerican men into medical school. A large amount of debt

5 years safety of fingolimod in real world: First results from PANGAEA, a non-interventional study of RRMS patients treated with fingolimod, on safety and adherence after 5 years of fingolimod in daily clinical practice (P5.365)

Abstract: Objective: PANGAEA (Post-Authorization Non-interventional GermansAfety of GilEnyA in RRMS patients) is a non-interventional study conducted in Germany to investigate long-term safety, effectiveness and patient reported outcomes. Background: Fingolimod(Gilenya®) is a sphingosine-1-phosphate receptor modulator approved for the treatment of relapsing MS. More than 160.000 patients have been treated with fingolimod; total patient exposure exceeded 368.000 patient years. Design/Methods: Recruitment into the study finished in December 2013. 4229 patients enrolled. By Jan 2017 over 300 patients finished the 5 year documentation period. In this interim analysis we present safety data from 5 years fingolimod treatment in daily clinical routine. Results: Over 5 years the yearly mean study discontinuation rate was 12%. App. 67% of patients that started the fingolimod treatment between 2011 and 2013 in PANGAEA are still on drug. App 79% of patients discontinuing the study also discontinued the fingolimod treatment. Most frequent reasons for premature study discontinuation(multiple answers possible) were patient’s decision (33%), adverse events(28%), switch of physician (12%) and disease progression (11%). Over 5 years the safety profile of fingolimod in real life is comparable to that observed in phase III clinical trials. Common adverse events are (reductions in lymphocytecounts), increase in liver enzyme values, upper respiratory tract infections(e.g. nasopharyngitis (9.9%); bronchitis (2.4%); cough (2.2%)), and potentially MS related adverse events like fatigue (3.4%) and depression (2.6%). App. 45% of the patients experienced no adverse events so far. 3.9% off all adverse events were rated as serious. Conclusions: The results of the 5 year interim analysis of PANGAEA support the positive benefit-risk profile fingolimod demonstrated in phase III clinical trials with real world evidence data. The frequency/nature of reported adverse events is consistent with previous findings from clinical trials. Study Supported by: This study was supported by the Novartis Pharma GmbH, Nuremberg, Germany. Disclosure: Dr. Ziemssen has received personal compensation for activities with Dr. Albrecht has received personal compensation for activities with Sanofi Genzyme, Novartis, and Biogen. Dr. Haas has received personal compensation for activities with Bayer Schering, Teva Aventis, Merck Serono, Biogen Idec, Allergan, Inc., and Octapharma as a consultant. Dr. Klotz has received personal compensation for activities with Genzyme, Novartis, CSL Behring, and Merck Serono as an advisory board member and a speaker. Dr. Lang has received personal compensation for activities with Novartis, Biogen Idec, Bayer, Teva, Serono and Genzyme. Dr. Lassek has received personal compensation for activities with Teva, Merck Serono, Genzyme -Sanofi, Novartis, Bayer, and Biogen. Dr. Schmidt received personal compensation for activities with Bayer Vital, Biogen Idec, MerckSerono, Teva, Sanofi, and Novartis as a scientific advisory board member and a speaker. Dr. Tackenberg has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Merck Serono, Novartis Pharma, and Teva Pharma as a speaker and consultant. Dr. Cornellissen has received personal compensation for activities with Novartis Pharma GmbH as an employee.

Eligibility for alirocumab or evolocumab treatment in 1090 hypercholesterolemic patients referred to a regional cholesterol treatment center with LDL cholesterol ≥70 mg/dL despite maximal-tolerated LDL-cholesterol-lowering therapy.

Abstract: Background Proprotein convertase subtilisin/kexin type 9 inhibitors, Praluent (alirocumab [ALI]) and Repatha (evolocumab [EVO]) have been approved as adjuncts to the standard-of-care maximal-tolerated dose (MTD) of low-density lipoprotein cholesterol (LDLC)-lowering therapy (LLT), statin therapy, in heterozygous (HeFH) (ALI or EVO) or homozygous (EVO) familial hypercholesterolemia, or clinical atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient (both). Since LDLC lowering has been revolutionized by ALI and EVO, specialty pharmaceutical pricing models will be applied to a mass market. Methods We applied US Food and Drug Administration (FDA) and insurance eligibility criteria for ALI and EVO to 1090 hypercholesterolemic patients serially referred over 3 years who then received ≥2 months maximal-tolerated dose of standard-of-care LDL cholesterol-lowering therapy (MTDLLT) with follow-up LDLC ≥70 mg/dL. MTDLLT did not include ALI or EVO, which had not been commercially approved before completion of this study. Results Of the 1090 patients, 140 (13%) had HeFH by clinical diagnostic criteria and/or CVD with LDLC >100 mg/dL despite ≥2 months on MTDLLT, meeting FDA insurance criteria for ALI or EVO therapy. Another 51 (5%) patients were statin intolerant, without HeFH or CVD. Conclusion If 13% of patients with HeFH-CVD and LDLC >100 mg/dL despite MTDLLT are eligible for ALI or EVO, then specialty pharmaceutical pricing models (~$14,300/year) might be used in an estimated 10 million HeFH-CVD patients. Whether the health care savings arising from the anticipated reduction of CVD events by ALI or EVO justify their costs in populations with HeFH-CVD and LDLC >100 mg/dL despite MTDLLT remains to be determined.

Osteochondroma of the Cuboid: A Case Report

Abstract: Osteochondromas are common benign exostoses with <1% of pedal occurrences. Several cases of osteochondromas have been previously reported in the foot and ankle but none from the cuboid. In the present study, we report a case of osteochondroma originating from the cuboid in a 29-year-old male patient. The patient presented with an aching and shooting pain to his left foot that had progressed during the course of 3 years. Originally diagnosed as a fibroma, the patient had undergone cortisone injections that did not help with his symptoms. Radiographic and magnetic resonance imaging revealed an osteochondroma to the patient's left cuboid. Surgical removal of the tumor confirmed the diagnosis. The patient had an uneventful postoperative recovery and had no recurrence after 1.5 years of follow-up. In conclusion, although osteochondromas are rare in the foot and ankle and most are benign, they can result in many symptoms and can impair patients' quality of life, such as occurred in our patient. Recommendations for surgical excision should be determined on a case-by-case basis.

Accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis. A study of 404 pulmonologists from 57 countries

Abstract: Methods: We conducted an international study of IPF diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts (n=34). Participants evaluated 60 consecutive cases of interstitial lung disease. Diagnostic agreement was measured using weighted kappa coefficient (κw). Outcome distinctions between IPF and other diffuse lung diseases were used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the C-index. Results: 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (κw =0.65 [IQR 0.53-0.72], P 20 years experience and MDT meeting attendance independently predicted prognostic accuracy of IPF diagnosis. The prognostic accuracy of academic physicians with >20 years experience (C-index=0.72, [IQR 0.0-0.73], p=0.229)) and non-university hospital physicians with more than 20 years experience, attending weekly MDT meetings (C-index=0.72, [IQR 0.70-0.72], p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 [IQR 0.72-0.75]. Conclusion: Experienced respiratory physicians working at university-based institutions make diagnoses of IPF with similar prognostic accuracy to an international panel of IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts.

Osteonecrosis and Thrombophilia: Pathophysiology, Diagnosis, and Treatment

Abstract: We describe three patients: two women, ages 47 and 69, and a man, age 54, with Ficat stages I, II, and I–II primary osteonecrosis at entry. Coagulation tests revealed heterozygosity for the G20210A prothrombin gene mutation, resistance to activated protein C, and heterozygosity for the factor V Leiden mutation, respectively. In two patients, ages 47 and 54, exogenous testosterone appeared to interact with the prothrombin and factor V Leiden mutations, promoting onset of osteonecrosis. Testosterone was stopped. In all three cases, long-term anticoagulation (4, 13, and 10 years) completely relieved pain, there was no joint collapse, and the Ficat stages were unchanged or improved. In patients with primary osteonecrosis (Ficat stages I–II) and major gene thrombophilias, long-term anticoagulation for 4, 13, and 10 years as in our three patients can ameliorate pain, restore normal joint function, prevent joint collapse, and lead to stable or improved X-rays and MRIs, providing a medical approach to treatment of primary osteonecrosis.