Outcomes of Common Peroneal Nerve Decompression.

PURPOSE: Common peroneal nerve (CPN) neuropathy is the most common lower extremity mononeuropathy. When delayed or no recovery from CPN neuropathy is suspected, surgical CPN decompression (CPND) is considered to relieve symptoms. This study aimed to evaluate patient outcomes post-CPND performed by a single surgeon at a tertiary medical center. METHODS: Patient outcomes after CPND performed by a single surgeon were reviewed. Motor, sensation, and pain scores post-CPND were assessed in 47 of the 46 patients. Patient demographics, including age, concomitant morbidities, time from injury to surgery, and body mass index (BMI), were also analyzed for correlations with outcomes after CPND by logistic regression. RESULTS: 29/34 patients with impaired motor function improved by at least one motor grade, 19/42 with altered sensation reported restored normal sensation, and 31/37 reported improved pain after CPND. No correlation of patient demographic factors with motor or pain improvement after CPND was observed. However, a BMI greater than 29.15 and a time between injury and surgery exceeding 506 days were associated with lower odds of reporting restored sensation. CONCLUSIONS: Operative decompression of CPN neuropathy improves objective motor scores and subjective sensation and pain scores.

Bridging Reconstruction With Interpositional Dermal Allograft Has Superior Healing Than Does Maximal Repair for Treatment of Large to Massive, Irreparable Rotator Cuff Tears-Secondary Analysis of a Randomized Control Trial.

PURPOSE: The purpose of this study was to compare the radiographic results of bridging rotator cuff reconstruction (BRR) with dermal allograft and maximal repair for large or massive, irreparable rotator cuff tears. METHODS: This was a secondary analysis of data from a single-center, blinded-observer, randomized controlled trial that examined clinical outcomes of BRR compared with maximal repair. A sample size of 30 patients with magnetic resonance imaging (MRI)-proven large or massive (>3 cm), retracted rotator cuff tears and/or involvement of 2 or more tendons were randomly allocated to 1 of 2 groups: maximal repair or BRR using dermal allograft. MRIs were obtained preoperatively and 1 year postoperatively. The primary outcome of this study was the retear rate on MRI. Secondary outcomes included progression of muscle atrophy and fatty infiltration. RESULTS: There was no difference in age or preoperative tear size between the 2 groups. Patients treated with BRR had decreased retear rate (21%) compared with patients who received maximal repair alone (87%). There was no difference in the number of patients who had progression of muscle atrophy (P = .088 for supraspinatus and P = .738 for infraspinatus) or fatty infiltration (P = .879 for supraspinatus and P = .693 for infraspinatus) between the 2 groups. A significant increase in mean postoperative supraspinatus muscle atrophy was identified in the maximal repair group (P = .034). CONCLUSIONS: The results of this secondary analysis of a randomized controlled trial comparing radiographic results of maximal repair versus BRR using dermal allograft in the treatment of large or massive rotator cuff tears show that BRR results in a significantly reduced structural failure rate and a trend toward better preservation of supraspinatus muscle mass compared with maximal repair. LEVEL OF EVIDENCE: Level I, secondary analysis of a randomized controlled trial.

Primary Rotator Cuff Bridging Reconstruction Shows Better Clinical and Radiographic Results Than Revision Bridging Reconstruction.

Purpose: To evaluate the outcome of revision rotator cuff bridging reconstruction (BR) as compared to primary BR in a large cohort of patients. Methods: A retrospective chart review was conducted for patients who underwent BR using dermal allograft for large/massive rotator cuff tears between 2010 and 2018. Patients who completed Western Ontario Rotator Cuff Index (WORC) and Disability of the Arm, Shoulder, and Hand (DASH) scores both pre- and postoperatively were included. Pre- and postoperative magnetic resonance imaging scans were compared to assess for differences in fatty infiltration, muscle atrophy, and graft status. Results: Eighty patients met the inclusion criteria, including 43 patients who underwent BR as a primary surgery and 37 patients who underwent revision BR. The mean follow-up duration was 5.7 ± 1.9 years in the primary group and 5.8 ± 2.0 years in the revision group. Both WORC and DASH scores significantly improved from pre- to postoperatively for both the primary and revision groups (P < .05). The primary group had significantly better postoperative WORC and DASH scores at 6 months, 1 year, and final follow-up (P < .05). Failure rate of the graft was higher in the revision group compared to primary group (14.3% vs 6.1%, respectively; P = .337), and the amount of fatty infiltration of supraspinatus and infraspinatus muscles significantly improved in patients who received primary BR compared to revision BR (P < .05). Conclusions: BR using dermal allograft for large/massive irreparable rotator cuff tears showed improvement of functional outcomes, with primary cases resulting in better improvement in patient-reported outcomes compared to revision cases. Primary BR was also associated with better postoperative fatty infiltration of supraspinatus and infraspinatus muscles. Level of Evidence: Level III, retrospective cohort study.

Diagnosis and management of Achilles tendon ailments: the Scottish mist.

The diagnosis and management of Achilles tendon ailments continue to be widely discussed by the scientific community. Also, the nomenclature used to describe the tendinopathic lesion in patients changed over the last decades together with the evolution in the knowledge of the physiopathology of Achilles tendinopathy, and unfortunately, through ignorance and possibly laziness, confusion still abounds. To emerge from these foggy paths, some clarifications are still necessary. The present Editorial tries to clarify some of these issues.

Presentation and Management of the Pediatric Trigger Finger: A Multicenter Retrospective Cohort Study.

PURPOSE: Pediatric trigger finger (PTF) is an acquired condition that is uncommon and anatomically complex. Currently, the literature is characterized by a small number of retrospective case series with limited sample sizes. This investigation sought to evaluate the presentation, management, and treatment outcomes of PTF in a large, multicenter cohort. METHODS: A retrospective review of pediatric patients with a diagnosis of PTF between 2009 and 2020 was performed at three tertiary referral hospitals. Patient demographics, PTF characteristics, treatment strategies, and outcomes were abstracted from the electronic medical records. Patients and families also were contacted by telephone to assess the downstream persistence or recurrence of triggering symptoms. RESULTS: In total, 321 patients with 449 PTFs were included at a mean follow-up of 3.9 ± 4.0 years. There were approximately equal numbers of boys and girls, and the mean age of symptom onset was 5.4 ± 5.1 years. The middle (34.7%) and index (11.6%) fingers were the most and least commonly affected digits, respectively. Overall, PTFs managed operatively achieved significantly higher rates of complete resolution compared with PTFs managed nonsurgically (97.1% vs 30.0%). Seventy-five percent of PTFs that achieved complete resolution with nonsurgical management did so within 6 months, and approximately 90% did so within 12 months. Patients with multidigit involvement, higher Quinnell grade at presentation, or palpable nodularity were significantly more likely to undergo surgery. There was no significant difference in the rate of complete resolution between splinted versus not splinted PTFs or across operative techniques. CONCLUSIONS: Only 30% of the PTFs managed nonsurgically achieved complete resolution. Splinting did not improve resolution rates in children treated nonsurgically. In contrast, surgical intervention has a high likelihood of restoring motion and function of the affected digit. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The impact of a metal artefact reduction algorithm on treatment planning for patients undergoing radiotherapy of the pelvis.

Background and purpose: Metallic implants cause artefacts in computed tomography (CT) images and can introduce significant errors to structure visualisation and dosimetric calculation within the radiotherapy planning process. This study evaluated an orthopaedic metal artefact reduction algorithm and its effect on the CT number, image noise, structure delineation, and treatment dose. Methods: Raw CT data were reconstructed using standard filtered back projection and an artefact reduction algorithm to create 'standard' and 'corrected' images. A phantom containing tissue-mimicking inserts and two titanium plugs was imaged. The average CT number was compared to baseline data acquired without metal inserts. Data from 11 pelvic external beam radiotherapy (EBRT) patients with bi- or uni-lateral hip implants were retrospectively analysed. The clinically used treatment plans were re-computed on the corrected images. A prostate-mimicking phantom containing metal 'implants' was imaged, and 11 observers contoured both reconstructions. Results: The artefact reduction algorithm improved the CT number in those areas most affected by metal artefacts and decreased noise by 19 % (P =.04) Changes in dose distributions on corrected images compared to those calculated using the current clinical protocol were clinically insignificant. Volumes contoured on the corrected phantom images had larger Dice coefficients than those contoured on the standard images (P =.001), as well as a 36 % lower standard deviation in volumes. Conclusion: This study demonstrates that the metal artefact reduction software reduces the error in CT numbers, can improve delineation accuracy, and can reduce inter-observer variability. It has the potential to streamline the planning pathway and improve treatment planning accuracy.

Pseudomonas aeruginosa in the Cystic Fibrosis Lung.

Cystic fibrosis is a common genetically inherited, multisystem disorder caused by loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an apically situated anion channel. In the lung, lack of CFTR leads to airway surface dehydration, mucociliary clearance failure and an acidic pH in which innate defence molecules are rendered ineffective. Infection occurs early in life, with P. aeruginosa dominating by adolescence. The characteristic features of the CF airway highlighted above encourage persistence of infection, but P. aeruginosa also possess an array of mechanisms with which they attack host defences and render themselves protected from antimicrobials. Early eradication is usually successful, but this is usually transient. Chronic infection is manifest by biofilm formation which is resistant to treatment. Outcomes for people with CF have improved greatly in the last few decades, but particularly so with the recent advent of small molecule CFTR modulators. However, despite impressive efficacy on lung function and exacerbation frequency, most people with chronic infection remain with their pathogens. There is an active pipeline of new treatments including anti-biofilm and anti-quorum sensing molecules and non-drug approaches such as bacteriophage. Studies are reviewed and challenges for future drug development considered.

Public Interest Group on Cancer Research: a successful patient-researcher partnership in Newfoundland and Labrador.

BACKGROUND: Partnering with patients and family members affected by cancer is essential for meaningful research, public engagement and outreach, and advocacy activities. OBJECTIVE: Our objective was to create a public interest group through an academic-community partnership focused on cancer research and public engagement. METHODS: A purposeful recruitment process was implemented to ensure a diverse and inclusive group. The group meets virtually and communicates by email. The group's activities focus on identifying the needs, priorities, and interests of cancer-affected individuals in the province; consultations; and designing research projects and public outreach activities together. Comprehensive meeting minutes are kept and used to distill discussion points. The work of the group is disseminated through a variety of channels. RESULTS: The public interest group includes 12 cancer patient and family member representatives, in addition to researchers. Discussions by the interest group identified key themes related to: (1) equity issues and regional disparity in provincial oncocare; (2) information needs; (3) need for patient empowerment and public understanding; and (4) family member and partner needs and experiences. To date, the group has co-designed a cancer research proposal and a public engagement/outreach activity. The group also provides consultations on cancer-related projects/public engagement activities and members act as patient partners in specific research and public engagement proposals. The group evolves over time, and increasingly advocates on behalf of cancer patients and families. Retention and satisfaction of the public partners with group activities have been high. The group's work and findings are disseminated to the Provincial Cancer Care Program, as well as to public and scientific stakeholders through local media, academic conferences and presentations, and a dedicated website. CONCLUSION: Public Interest Group on Cancer Research represents a highly successful patient-researcher partnership in oncology. It designs meaningful and patient-oriented studies and outreach activities in cancer. It also elevates and widely supports cancer patient and family voice.

Cancer patients and their family members have unique and lived experience with the condition. Therefore, collaborating with them is important in cancer science. We aimed to create such a collaboration in Newfoundland and Labrador, Canada. In 2021, we successfully formed our diverse collaborative group. Currently, our group includes 12 public representatives. We meet online and discuss matters important to members. We also design studies and events together. Our discussions have identified four topics that need further research and policy changes such as information needs and unique needs of caregivers and family members. Our activities expand over time. For example, lately we started to advocate for other cancer patients and families. In conclusion, we formed a successful cancer patient, family member, and researcher collaborative group. Our work informs the public, healthcare systems, and scientists on important cancer related matters.

Metabolic modeling-based drug repurposing in Glioblastoma.

The manifestation of intra- and inter-tumor heterogeneity hinders the development of ubiquitous cancer treatments, thus requiring a tailored therapy for each cancer type. Specifically, the reprogramming of cellular metabolism has been identified as a source of potential drug targets. Drug discovery is a long and resource-demanding process aiming at identifying and testing compounds early in the drug development pipeline. While drug repurposing efforts (i.e., inspecting readily available approved drugs) can be supported by a mechanistic rationale, strategies to further reduce and prioritize the list of potential candidates are still needed to facilitate feasible studies. Although a variety of 'omics' data are widely gathered, a standard integration method with modeling approaches is lacking. For instance, flux balance analysis is a metabolic modeling technique that mainly relies on the stoichiometry of the metabolic network. However, exploring the network's topology typically neglects biologically relevant information. Here we introduce Transcriptomics-Informed Stoichiometric Modelling And Network analysis (TISMAN) in a recombinant innovation manner, allowing identification and validation of genes as targets for drug repurposing using glioblastoma as an exemplar.

Integrated multi-omics analyses reveals molecules governing sperm metabolism potentially influence bull fertility.

Bull fertility is of paramount importance in bovine industry because semen from a single bull is used to breed several thousands of cows; however, so far, no reliable test is available for bull fertility prediction. In the present study, spermatozoa from high- and low-fertility bulls were subjected to high-throughput transcriptomic, proteomic and metabolomic analysis. Using an integrated multi-omics approach the molecular differences between high- and low-fertility bulls were identified. We identified a total of 18,068 transcripts, 5041 proteins and 3704 metabolites in bull spermatozoa, of which the expression of 4766 transcripts, 785 proteins and 33 metabolites were dysregulated between high- and low-fertility bulls. At transcript level, several genes involved in oxidative phosphorylation pathway were found to be downregulated, while at protein level genes involved in metabolic pathways were significantly downregulated in low-fertility bulls. We found that metabolites involved in Taurine and hypotaurine metabolism were significantly downregulated in low-fertility bulls. Integrated multi-omics analysis revealed the interaction of dysregulated transcripts, proteins and metabolites in major metabolic pathways, including Butanoate metabolism, Glycolysis and gluconeogenesis, Methionine and cysteine metabolism, Phosphatidyl inositol phosphate, pyrimidine metabolism and saturated fatty acid beta oxidation. These findings collectively indicate that molecules governing sperm metabolism potentially influence bull fertility.

Genom-wide analysis identifies single nucleotide polymorphism variations and altered pathways associated with poor semen quality in breeding bulls.

The reason for poor semen quality among the breeding bulls is not well understood. In the present study, we performed high-throughput RNAseq analysis of spermatozoa to identify the SNPs present in good and poor-quality semen-producing Holstein Friesian breeding bulls. A total of 21,360 and 44,650 SNPs were identified in good and poor-quality semen with a minimum read depth of 20, among which 4780 and 8710 novel variants were observed in good and poor-quality semen, respectively. Greater SNPs and indels variations were observed in poor compared to good-quality semen. In poor-quality semen, SNP variations were observed in ZNF280B, SLC26A2, DMXL1, OR52A1, MACROD2 and REV1 genes, which are associated with regulation of spermatogenesis, post-testicular maturation, Cl- channel activity, V-ATPase-mediated intracellular vesicle acidification, a mono-ADP-ribosyl hydrolase and ATR-Chk1 checkpoint activation. GO analysis of filtered genes with significant variations between good and poor-quality semen showed enrichment in important pathways related to semen quality such as MAPK signalling pathway, Akt signalling pathway, focal adhesion, cAMP signalling pathway, and Rap1 signalling pathway. Network analysis of filtered genes in poor-quality semen showed variations in pathways of purine metabolism, pyrimidine metabolism, prolactin signalling pathway and RNA cap-binding complex. It is inferred that SNP in genes involved in maintaining sperm functions could be the reason for poor-quality semen production in bulls, and the identified SNPs hold potential to be used as biomarkers for semen quality in bulls.

An Update on CFTR Modulators as New Therapies for Cystic Fibrosis.

Over the past decade there have been significant developments in the field of Cystic Fibrosis Transmembrane Regulator modulator drugs. Following treatment in patients with cystic fibrosis with common gating mutations using the potentiator drug ivacaftor, successive development of corrector drugs used in combination has led to highly effective modulator therapy being available to more than 85% of the cystic fibrosis population over 12 years of age in the form of elexacaftor/tezacaftor/ivacaftor. In this article, we review the evidence from clinical trials and mounting real-world observational and registry data that demonstrates the impact highly effective modulators have on both pulmonary and extra-pulmonary manifestations of cystic fibrosis. As clinical trials progress to younger patient groups, we discuss the challenges to demonstrating drug efficacy in early life, and also consider practicalities of drug development in an ever-shrinking modulator-naïve population. Drug-drug interactions are an important consideration in people with cystic fibrosis, where polypharmacy is commonplace, but also as the modulated population look to remain healthier for longer, we identify trials that aim to address treatment burden too. Inequity of care, through drug cost or ineligibility for modulators by genotype, is widening without apparent strategies to address this; however, we present evidence of hopeful early-stage drug development for non-modulatable genes and summarise the current state of gene-therapy development.

Interposition Graft Bridging Reconstruction of Irreparable Rotator Cuff Tears Using Acellular Dermal Matrix: Medium-Term Results.

PURPOSE: In this study, we aimed to evaluate the medium-term clinical outcomes for patients who underwent bridging reconstruction. METHODS: A retrospective chart review was conducted for all patients who underwent bridging reconstruction between 2010 and 2018. Patients who were missing either pre- or postoperative outcome scores were excluded. All included patients completed self-reported questionnaires (Western Ontario Rotator Cuff [WORC] and Disabilities of the Arm, Shoulder and Hand [DASH]) pre- and postoperatively at 6 months, 1 year, and annually thereafter. All scores were reported out of 100. RESULTS: Ninety-one patients initially met our inclusion criteria, and 33 were excluded owing to lack of either pre- or postoperative outcome scores. Nine patients were lost to follow-up; therefore, 49 patients were finally evaluated, including 30 males (61.2%) and 19 females (38.8%) with an age of 59.6 ± 10.4 years (mean ± standard deviation) and mean follow-up of 5.3 years (range 2 to 9). Both WORC and DASH scores significantly improved from pre- to postoperatively (WORC: 69.6 ± 12.2 to 27.9 ± 23.7, P < .001; DASH: 51.5 ± 17.5 to 24.5 ± 23.0, P = .001). For WORC and DASH, 92% and 74% of patients, respectively, met the minimal clinical importance difference. CONCLUSION: Our results showed that patients' clinical outcome scores significantly improved with an average of 5-year follow-up, which demonstrates that bridging reconstruction is a safe procedure with promising midterm clinical outcomes. LEVEL OF EVIDENCE: IV, retrospective case series.

ERS International Congress 2020: highlights from the Paediatric Assembly.

In this review, the Paediatric Assembly of the European Respiratory Society (ERS) presents a summary of the highlights and most relevant findings in the field of paediatric respiratory medicine presented at the virtual ERS International Congress 2020. Early Career Members of the ERS and Chairs of the different Groups comprising the Paediatric Assembly discuss a selection of the presented research. These cover a wide range of research areas, including respiratory physiology and sleep, asthma and allergy, cystic fibrosis, respiratory infection and immunology, neonatology and intensive care, epidemiology, bronchology and lung and airway development. Specifically, we describe the long-term effect in lung function of premature birth, mode of delivery and chronic respiratory conditions such as cystic fibrosis. In paediatric asthma, we present risk factors, phenotypes and their progression with age, and the challenges in diagnosis. We confirm the value of the lung clearance index to detect early lung changes in cystic fibrosis. For bronchiectasis treatment, we highlight the importance of identifying treatable traits. The use of biomarkers and genotypes to identify infants at risk of long-term respiratory morbidity is also discussed. We present the long-term impact on respiratory health of early life and fetal exposures to maternal obesity and intrauterine hypoxia, mechanical ventilation hyperoxia, aeroallergens, air pollution, vitamin A deficient intake and bronchitis. Moreover, we report on the use of metabolomics and genetic analysis to understand the effect of these exposures on lung growth and alveolar development. Finally, we stress the need to establish multidisciplinary teams to treat complex airway pathologies.

Minimal manifestation status and prednisone withdrawal in the MGTX trial.

OBJECTIVE: To examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG). METHODS: This study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18-65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 months) with complete withdrawal of prednisone was compared between the thymectomy plus prednisone and prednisone alone groups. RESULTS: Patients with MG in the thymectomy plus prednisone group achieved sustained MMS with complete withdrawal of prednisone more frequently (64% vs 38%) and quickly compared to the prednisone alone group (median time 30 months vs no median time achieved, p < 0.001) over the 5-year study period. Prednisone-associated adverse symptoms were more frequent in the prednisone alone group and distress level increased with higher doses of prednisone. CONCLUSIONS: Thymectomy benefits patients with MG by increasing the likelihood of achieving sustained MMS with complete withdrawal of prednisone. CLINICALTRIALSGOV IDENTIFIER: NCT00294658. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with generalized MG with AChR antibody, those receiving thymectomy plus prednisone are more likely to attain sustained MMS and complete prednisone withdrawal than those on prednisone alone.

Irritant-evoked activation and calcium modulation of the TRPA1 receptor.

The transient receptor potential ion channel TRPA1 is expressed by primary afferent nerve fibres, in which it functions as a low-threshold sensor for structurally diverse electrophilic irritants, including small volatile environmental toxicants and endogenous algogenic lipids1. TRPA1 is also a 'receptor-operated' channel whose activation downstream of metabotropic receptors elicits inflammatory pain or itch, making it an attractive target for novel analgesic therapies2. However, the mechanisms by which TRPA1 recognizes and responds to electrophiles or cytoplasmic second messengers remain unknown. Here we use strutural studies and electrophysiology to show that electrophiles act through a two-step process in which modification of a highly reactive cysteine residue (C621) promotes reorientation of a cytoplasmic loop to enhance nucleophilicity and modification of a nearby cysteine (C665), thereby stabilizing the loop in an activating configuration. These actions modulate two restrictions controlling ion permeation, including widening of the selectivity filter to enhance calcium permeability and opening of a canonical gate at the cytoplasmic end of the pore. We propose a model to explain functional coupling between electrophile action and these control points. We also characterize a calcium-binding pocket that is highly conserved across TRP channel subtypes and accounts for all aspects of calcium-dependent TRPA1 regulation, including potentiation, desensitization and activation by metabotropic receptors. These findings provide a structural framework for understanding how a broad-spectrum irritant receptor is controlled by endogenous and exogenous agents that elicit or exacerbate pain and itch.

Impact of Treatment with Direct Acting Antiviral Drugs on Glycemic Control in Patients with Hepatitis C and Diabetes Mellitus.

AIM: To assess the effect of treating chronic hepatitis C virus (HCV) infection with direct acting antiviral drugs (DAAs) on glycemic control in patients with concomitant diabetes mellitus (DM). METHODS: We performed a retrospective case-control study in a viral hepatitis ambulatory clinic in Shreveport, Louisiana, during the period 11/01/2014 to 12/31/2017. All the clinic patient ages 18 years and above with treatment-naïve/biopsy-proven chronic hepatitis C and DM (hemoglobin A1C level ≥ 6.5%) who were eligible for treatment were included in the study. Of 118 such patients, 59 were treated with oral DAAs for 8-12 weeks with the goal of achieving a sustained virologic response (SVR). A control group of 59 patients did not receive treatment for their hepatitis C and was followed in the clinic. Patients in the control group did not receive treatment either due to insurance issues or refusal of hepatitis C treatment. RESULTS: Fifty-five of the 59 patients treated with DAAs (93%) achieved a SVR. Six months after treatment completion, their mean ± SEM HbA1C level had decreased by 1.1 ± 0.03% (P < 0.0001). Four of the 59 patients treated with DAAs did not achieve a SVR. Their mean HbA1C 6 months after treatment completion had increased by 0.8 ± 0.2%. Furthermore, there was no improvement in HbA1C levels over time in the untreated group (mean HbA1C increase, 0.2 ± 0.05%; P < 0.0001 vs. the treatment group, which had a mean HbA1C decrease of 0.9 ± 0.2%). CONCLUSION: This controlled study demonstrated that treatment of chronic hepatitis C with DAAs results in statistically significant and meaningful reductions in hemoglobin A1C levels in patients with coexisting diabetic mellitus if a SVR is achieved.

The synergistic effect of preoperative opioid use and many associated preoperative predictors of poor outcome in the trauma patient population.

OBJECTIVE: The purpose of this study is to investigate if preoperative opioid use is associated with other predictors of poor outcome and the effect of these factors on complications. We hypothesized that preoperative opioid use (POU) is associated with increased rates of postoperative complications. DESIGN: Retrospective case control study. SETTING: Academic level-1 trauma center. PATIENTS/PARTICIPANTS: Patients with long bone, lower extremity fractures requiring operative fixation. INTERVENTION: N/A. MAIN OUTCOME MEASURES: Postoperative hospital admissions, emergency room (ER) visits, and reoperations. RESULTS: 399 patients (opioid naïve [ON] 80.2%, Age 38, 95% CI 35.9-39.6) were reviewed. Patients who had POU were older (P = 0.004), had higher BMI (P = 0.03), proportion of females (P < 0.001), tobacco use (P < 0.001), proportion of American Society of Anesthesiologist (ASA) class ≥ 3 (P < 0.001), and rates of substance use disorder (SUD) (P < 0.001). POU was associated with prolonged opiate use at 6 months (60.8%), 1 year (43.0%), higher rates of postoperative readmissions (18.1%), ER visits (17.2%), reoperations (17.5%), and complications (Odds Ratio [OR]: 2.4, P < 0.01). The risk of complication increased synergistically with the addition of other predictors: less than a high school education (OR: 4.6, P = 0.001); ASA class ≥3 (OR: 5.6, P < 0.001). All three factors combined also increased risk of complication synergistically (OR: 9.1, P = 0.003). CONCLUSIONS: Our study demonstrates that many predictors of poor outcome frequently accompany POU. POU combined with many of these predictors synergistically increases the risk of complication. Outcomes-based payment models should reflect this expected rate of readmissions, ER visits and complications in this group. Patients with POU should be targeted with multi-disciplinary interventions aimed to modify these risk factors.

Anthropogenic electromagnetic fields (EMF) influence the behaviour of bottom-dwelling marine species.

Many marine animals have evolved sensory abilities to use electric and magnetic cues in essential aspects of life history, such as to detect prey, predators and mates as well as to orientate and migrate. Potential disruption of vital cues by human activities must be understood in order to mitigate potential negative influences. Cable deployments in coastal waters are increasing worldwide, in capacity and number, owing to growing demands for electrical power and telecommunications. Increasingly, the local electromagnetic environment used by electro- and magneto-sensitive species will be altered. We quantified biologically relevant behavioural responses of the presumed, magneto-receptive American lobster and the electro-sensitive Little skate to electromagnetic field (EMF) emissions of a subsea high voltage direct current (HVDC) transmission cable for domestic electricity supply. We demonstrate a striking increase in exploratory/foraging behaviour in skates in response to EMF and a more subtle exploratory response in lobsters. In addition, by directly measuring both the magnetic and electric field components of the EMF emitted by HVDC cables we found that there were DC and unexpectedly AC components. Modelling, restricted to the DC component, showed good agreement with measured results. Our cross-disciplinary study highlights the need to integrate an understanding of the natural and anthropogenic EMF environment together with the responses of sensitive animals when planning future cable deployments and predicting their environmental effects.

The Reduction of Heterotopic Ossification Incidence After Hip Arthroscopy in Patients Treated With Selective Cyclooxygenase 2 Inhibitor (Celecoxib).

PURPOSE: To evaluate the effectiveness of celecoxib, a selective cyclooxygenase 2 inhibitor, in reducing heterotopic ossification (HO) after hip arthroscopic surgery and to evaluate celecoxib's impact on clinical outcomes. METHODS: We performed a retrospective review of patients who received hip arthroscopy performed by the same surgeon between January 1, 2012, and December 31, 2016. Patients who had an allergy to sulfa drugs, had pre-existing HO or previous surgery on the operative side, or failed to complete radiographic follow-up at 6 months postoperatively were excluded. Patients in the treatment group received 400 mg of celecoxib postoperatively for 6 weeks, whereas the control group received no postoperative celecoxib. The incidence of HO was assessed using anteroposterior radiographs obtained at 6 months, 1 year, and 2 years postoperatively. Patients completed the International Hip Outcome Tool 33 survey, and the proportion of patients who met the minimal clinically important difference, substantial clinical benefit (SCB), and absolute SCB was calculated. RESULTS: A total of 559 patients were identified. After application of the exclusion criteria, 454 patients were included in the study (211 in control group and 243 in treatment group). The overall incidence of HO was 20.3% (n = 92). The treatment group had a significantly lower incidence of HO at 6 months (P = .006), 1 year (P < .001), and 2 years (P = .008) postoperatively. At 2 years postoperatively, the treatment group had a significantly higher International Hip Outcome Tool 33 score on average: 64.2 versus 57.3 (P = .023). No significant difference in the proportion of patients reaching the minimal clinically important difference, SCB, or absolute SCB was found at any of the postoperative time points. CONCLUSION: The findings of this study suggest that a prophylactic treatment regimen of 400 mg of celecoxib once daily for 6 weeks significantly reduces the incidence of HO formation after hip arthroscopic surgery; however, it did not impact clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective, comparative case-control study.