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Background: Carpal tunnel syndrome (CTS), trigger finger (TF), and De Quervain tenosynovitis (DQ) are 3 common pathologies of the hand often treated with relatively simple surgical procedures. However, outcomes from these procedures can be compromised by postoperative complications. The aim of this study was to evaluate the association between diabetes, tobacco use, and obesity and the incidence of postoperative complications. Methods: We reviewed 597 patients treated surgically for CTS, TF, or DQ from 2010 to 2015. We used bivariate and multivariate analyses to assess independent associations between diabetes, tobacco use, obesity, and surgical complications and compared the incidences with healthier patients without these comorbidities. We also looked at patients with overlapping diagnoses of these comorbidities. Results: Bivariate analysis showed that patients with diabetes and smokers were more likely to have a surgical complication. Multivariate analysis showed diabetes and tobacco use as independent predictors of complications. The disease states or combinations placing patients at the highest risk of a postoperative complication were the diabetic-smoker-obese, diabetic-smoker, diabetic-obese, diabetic, and smoker-obese groups. The diabetic-smoker-obese patient population had a 42.02% predicted rate of postoperative complications. Conclusions: Diabetes and tobacco use are independent risk factors for complications after operative treatment of CTS, TF, and DQ. Obesity when coexisting with diabetes mellitus (DM) and/or tobacco use increased the risk of complications. When the 3 patient factors evaluated, DM, obesity, and tobacco use, were present, the rate of complications was 42.02%. Careful assessment and discussion should occur before proceeding with operative treatment for simple hand conditions in patients with the risk factors studied.

Background An extended trochanteric osteotomy (ETO) safely addresses femoral component removal during challenging revision total hip arthroplasty. However, no prior study has evaluated whether a difference in axial stability exists between ETO closure performed before (reconstitution) or after (scaffolding) canal preparation and stem impaction. We hypothesized that given the absence of clinical reports of outcome differences despite the wide use of both practices, no significant difference in the initial axial stability would exist between the 2 fixation techniques. Methods ETOs were performed and repaired using the reconstitution technique for the 6 right-sided femora and the scaffolding technique for the six left-sided femora. The 195-mm long, 3.5°-tapered splined titanium monobloc stems were impacted into 6 matched pairs of human fresh cadaveric femora. Three beaded cables were placed in a standardized fashion on each specimen, 1 for prophylaxis against osteotomy propagation during reaming/impaction and 2 to close the ETO. Stepwise axial loading was performed to 2600 N or until failure, which was defined as subsidence >5 mm or femoral/cable fracture. Results All specimens successfully resisted axial testing, with no stem in either ETO repair group subsiding >2 mm. The mean subsidence for the reconstitution group was 0.9 ± 0.4 mm, compared to 1.2 ± 0.5 mm for the scaffolding group (P = .2). Conclusion In this cadaveric model with satisfactory proximal bone stock, no difference existed between the reconstitution and scaffolding ETO repair techniques, and both provide sufficient immediate axial stability in a simulated revision total hip arthroplasty setting under physiologic loads.

BACKGROUND: The number of solitary pulmonary nodules to be evaluated is expected to increase and therefore we need to improve diagnostic and therapeutic tools to approach these nodules. To prevent patients from futile invasive procedures and receiving treatment without histological confirmation of cancer, we evaluated the value of virtual bronchoscopy navigation to obtain a diagnosis of the solitary pulmonary nodule in a real-world clinical setting.METHODS: In the NAVIGATOR single center, prospective, observational cohort study patients underwent a virtual bronchoscopy navigation procedure with or without guide sheet tunnelling to assess a solitary pulmonary nodule. Nodules were considered not accessible if a diagnosis could not be obtained by either by CT-guided transthoracic biopsy or conventional bronchoscopy.RESULTS: Between February 2021 and January 2022 35 patients underwent the virtual bronchoscopy navigation procedure. The overall diagnostic yield was 77% and was dependent on size of the nodule and chosen path, with highest yield in lesions with an airway path. Adverse events were few and manageable.CONCLUSION: Virtual bronchoscopy navigation with or without sheet tunnelling is a new technique with a good diagnostic yield, also in patients in whom previously performed procedures failed to establish a diagnosis and/or alternative procedures are considered not feasible based on expected yield and/or safety. Preventing futile or more invasive procedures like surgery or transthoracic punctures with a higher complication rate is beneficial for patients, and allowed treatment adaptation in two-third of the analyzed patient population.

Background Instability constitutes over 20% of revisions after total hip arthroplasty (THA). Dual mobility (DM) designs were introduced as a solution to this problem. However, the few publications that have reported promising results for monobloc DM constructs have been limited by sample size or length of follow-up. The purpose of this study is to evaluate mid-term outcomes (minimum 5-year follow-up) of a single-surgeon series utilizing a monobloc DM acetabular component in patients with high risk for dislocation. Methods This is a single-surgeon consecutive series of 207 primary THAs implanted with a monobloc DM component in patients who were considered at high risk for dislocation. Patient demographics and case-specific data were collected retrospectively. All patients had a minimum of 5-year follow-up. The Mann-Whitney U test was used to assess continuous variables, whereas categorical variables were analyzed using the chi-square test. Survival probability was calculated using the Kaplan-Meier method. Results Radiographic analysis did not reveal acetabular radiolucency in any patients, and there were no revisions for aseptic loosening. In addition, there were no dislocations. Seven of 205 patients (3.4%) were revised, 5 on the femoral side due to periprosthetic fracture and the remaining two for infection. Survivorship of the acetabular component from revision was 99%. The mean Veteran RAND (VR-12) physical score improved from 7 (standard deviation [SD]: 13.7) preoperatively to 9.5 (SD: 17.6) at the final follow-up. Similarly, the hip disability osteoarthritis score improved from 8 (SD: 17.9) preoperatively to 21.2 (SD: 37). Conclusion Monobloc DM components reliably prevent dislocation after primary THA in high-risk patients. At mid-term follow-up, this DM monobloc component demonstrates excellent implant survivorship, radiographic fixation, and improved functional outcomes.

Due to the declining number of scientifically trained physicians and increasing demand for high-quality literature, our institution pioneered a seven-year Physician Scientist Training Program (PSTP) to provide research-oriented residents the knowledge and skills for a successful academic career. The present study sought to identify orthopaedic surgeons with MD/PhD degrees, residency programs with dedicated research tracks, and to assess the effectiveness of the novel seven-year program in training prospective academic orthopaedic surgeons. Surgeons with MD/PhD degrees account for 2.3% of all 3,408 orthopaedic faculty positions in U.S. residency programs. During the last 23 years, our PSTP residents produced 752 peer-reviewed publications and received $349,354 from 23 resident-authored extramural grants. Eleven of our seven-year alumni practice orthopaedic surgery in an academic setting. The seven-year PSTP successfully develops clinically trained surgeon scientists with refined skills in basic science and clinical experimental design, grant proposals, scientific presentations, and manuscript preparation. (Journal of Surgical Orthopaedic Advances 31(3):144-149, 2022).

The presence of excessive concentrations of nitrate in industrial wastewaters, agricultural runoff, and some groundwaters constitutes a serious issue for both environmental and human health. As a result, there is considerable interest in the possibility of converting nitrate to the valuable product ammonia by electrochemical means. In this work, we demonstrate the efficacy of a novel flow cathode system coupled with ammonia stripping for effective nitrate removal and ammonia generation and recovery. A copper-loaded activated carbon slurry (Cu@AC), made by a simple, low-cost wet impregnation method, is used as the flow cathode in this novel electrochemical reactor. Use of a 3 wt % Cu@AC suspension at an applied current density of 20 mA cm

Titanium tapered stems (TTS) achieve fixation in the femoral diaphysis and are commonly used in revision total hip arthroplasty. The initial stability of a TTS is critical, but the minimum contact length needed and impact of implant-specific taper angles on axial stability are unknown. This biomechanical study was performed to better guide operative decision-making by addressing these clinical questions.Two TTS with varying conical taper angles (2° spline taper vs 3.5° spline taper) were implanted in 9 right and left matched fresh human femora. The proximal femur was removed, and the remaining femoral diaphysis was prepared to allow for either a 2 cm (n = 6), 3 cm (n = 6), or 4 cm (n = 6) cortical contact length with each implanted stem. Stepwise axial load was then applied to a maximum of 2600N or until the femur fractured. Failure was defined as either subsidence5 mm or femur fracture.All 6 femora with 2 cm of stem-cortical contact length failed axial testing, a significantly higher failure rate (P.02) than the 4 out of 6 femora and all 6 femora that passed testing at 3 cm and 4 cm, respectively, which were not statistically different from each other (P = .12). Taper angle did not influence success rates, as each matched pair either succeeded or failed at the tested contact length.4 cm of cortical contact length with a TTS demonstrates reliable initial axial stability, while 2 cm is insufficient regardless of taper angle. For 3 cm of cortical contact, successful initial fixation can be achieved in most cases with both taper angle designs.

Viral hijacking of microtubule (MT)-dependent transport is well understood, but several viruses also express discrete MT-associated proteins (vMAPs), potentially to modulate MT-dependent processes in the host cell. Specific roles for vMAP-MT interactions include subversion of antiviral responses by P3, an isoform of the P protein of rabies virus (RABV; genus Lyssavirus), which mediates MT-dependent antagonism of interferon (IFN)-dependent signal transducers and activators of transcription 1 (STAT1) signaling. P3 also undergoes nucleocytoplasmic trafficking and inhibits STAT1-DNA binding, indicative of intranuclear roles in a multipronged antagonistic strategy. MT association/STAT1 antagonist functions of P3 correlate with pathogenesis, indicating potential as therapeutic targets. However, key questions remain, including whether other P protein isoforms interact with MTs, the relationship of these interactions with pathogenesis, and the extent of conservation of P3-MT interactions between diverse pathogenic lyssaviruses. Using super-resolution microscopy, live-cell imaging, and immune signaling analyses, we find that multiple P protein isoforms associate with MTs and that association correlates with pathogenesis. Furthermore, P3 proteins from different lyssaviruses exhibit variation in intracellular localization phenotypes that are associated with STAT1 antagonist function, whereby P3-MT association is conserved among lyssaviruses of phylogroup I but not phylogroup II, while nucleocytoplasmic localization varies between P3 proteins of the same phylogroup within both phylogroup I and II. Nevertheless, the divergent P3 proteins retain significant IFN antagonist function, indicative of adaptation to favor different inhibitory mechanisms, with MT interaction important to phylogroup I viruses. IMPORTANCE Lyssaviruses, including rabies virus, cause rabies, a progressive encephalomyelitis that is almost invariably fatal. There are no effective antivirals for symptomatic infection, and effective application of current vaccines is limited in areas of endemicity, such that rabies causes ~59,000 deaths per year. Viral subversion of host cell functions, including antiviral immunity, is critical to disease, and isoforms of the lyssavirus P protein are central to the virus-host interface underpinning immune evasion. Here, we show that specific cellular interactions of P protein isoforms involved in immune evasion vary significantly between different lyssaviruses, indicative of distinct strategies to evade immune responses. These findings highlight the diversity of the virus-host interface, an important consideration in the development of pan-lyssavirus therapeutic approaches.

Sharyn A Roodenburg,1,2 Karin Klooster,1,2 Jorine E Hartman,1,2 T David Koster,1,2 Marlies van Dijk,1,2 Dirk-Jan Slebos1,2 1Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; 2Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The NetherlandsCorrespondence: Sharyn A RoodenburgDepartment of Pulmonary Diseases, AA11, University Medical Center Groningen, Hanzeplein 1, Groningen, 9713, GZ, The NetherlandsTel +31 50 361 9194Fax +31 050 3619320Email s.a.roodenburg@umcg.nlBackground: Endobronchial valve (EBV) treatment is an effective treatment for patients with severe emphysema. Revision bronchoscopies after endobronchial valve treatment can be essential to prolong the effect of treatment or address long-term complications.Purpose: To evaluate the indications, endoscopic findings and outcomes of revision bronchoscopies and investigate if any predictors for granulation tissue formation, after EBV treatment, can be identified.Patients and Methods: Patients who underwent EBV treatment between 2016 and 2019 in our hospital, as routine care, were included. If a patient underwent a revision bronchoscopy, data regarding revision bronchoscopies, including indication, finding, intervention and pulmonary function testing (PFT) after revision bronchoscopy were analysed.Results: One hundred seventy-nine patients were included of which 41% required at least one revision bronchoscopy. In 43% of the revision bronchoscopy patients, the indication was loss of initial treatment effect. In 53% of the revision bronchoscopy patients, granulation tissue was found to be the underlying cause. Valve replacement(s) were performed in 51% of the revision bronchoscopy cases. Permanent valve removal was required in 13% of all patients. Overall, revision bronchoscopies led to improvements in PFT outcomes for patients experiencing no or a loss of initial treatment effect. No clinically relevant predictors for granulation tissue formation were identified.Conclusion: Performing a revision bronchoscopy after EBV treatment is a useful procedure leading to an improved treatment effect in most patients. Granulation tissue formation, causing valve dysfunction, is the most common cause of longer term problems.Keywords: bronchoscopy, lung volume reduction, one-way valve, COPD

Introduction Knee osteoarthritis (OA) is a chronic pathology that is treated across multiple specialties. Opioid prescribing practices for knee OA have not been described on a national level. The purpose of this study was to (1) investigate the trends in opioid prescriptions for knee OA, (2) characterize and identify predominant opioid based medications prescribed for knee OA, and (3) identify patient- and provider-related factors influencing opioid prescribing patterns in the treatment of knee OA in the outpatient setting. Methods The National Ambulatory Medical Care Survey (NAMCS) was used to identify all patients in the United States who presented to an outpatient clinic for knee OA between 2007 and 2016. New opioid prescriptions were determined using a previously published algorithm. Generalized linear models were used to assess trends. Results A total of 41,389,332 patients were included, of which 12.8% were prescribed an opioid-based medication. Opioid prescription rose from 2007/2008 to 2013/2014. Analysis of the opioid type demonstrated that the prescription of hydrocodone-based medication and "other" traditional opioids followed the aforementioned trends. However, tramadol prescription demonstrated a sustained increase throughout the years peaking at 2015/2016. Patient income in the lowest quartile, a worker's compensation status, and depression were independently associated with higher odds of opioid prescription for knee OA. Conclusions Opioid prescription for knee OA remains high. Decreases in traditional opioid prescription have been countered by increase in tramadol prescription. The risks and addictive potential of tramadol and patient and provider risk factors should be emphasized.

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PurposeClose-contact rates are thought to be a significant driving force behind the dynamics of transmission for many infectious respiratory diseases. Efforts to control such infections typically focus on the practice of strict contact-avoidance measures. Yet, contact rates and their relation to transmission, and the impact of control measures, are seldom quantified. Here, we quantify the response of contact rates, transmission and new cases of COVID-19 to public health contact-restriction orders, and the associations among these three variables, in the Canadian province of British Columbia (BC) and within its two most densely populated regional health authorities: Fraser Health Authority (FHA) and Vancouver Coastal Health Authority (VCHA).MethodsWe obtained time series for self-reported close-contact rates from the BC Mix COVID-19 Survey, new reported cases of COVID-19 from the BC Center for Disease Control, and transmission rates based on dynamic model fits to reported cases. Our study period was from September 13, 2020 to February 19, 2021, during which three public health contact-restriction orders were introduced (October 26, November 7 and November 19, 2020). We used segmented linear regression to quantify impacts of public health orders, Pearson correlation to assess the instantaneous relation between contact rates and transmission, and vector autoregressive modeling to study the lagged relations among the three variables.ResultsOverall, declines in contact rates and transmission occurred concurrently with the announcement of public health orders, whereas declines in new cases showed a reporting delay of roughly two weeks. The impact of the first public health order (October 26, 2020) on contact rates and transmission was more pronounced than that of the other two health orders. Contact rates and transmission on the same day were strongly correlated (correlation coefficients = 0.64, 0.53 and 0.34 for BC, FHA, and VCHA, respectively). Moreover, contact rates were a significant time-series driver of COVID-19 and explained roughly 30% and 18% of the variation in new cases and transmission, respectively. Interestingly, increases in transmission and new cases were followed by reduced rates of contact: overall, average daily cases explained about 10% of the variation in provincial contact rates.ConclusionWe show that close-contact rates were a significant driver of transmission of COVID-19 in British Columbia, Canada and that they varied in response to public health orders. Our results also suggest a possible feedback, by which contact rates respond to recent changes in reported cases. Our findings help to explain and validate the commonly assumed, but rarely measured, response of close contact rates to public health guidelines and their impact on the dynamics of infectious diseases.

Introduction Bronchoscopic lung volume reduction treatment with one-way valves is an effective guideline treatment option for patients with severe emphysema. However, important challenges and adverse reactions may occur after treatment. Areas covered This review summarizes the complications after endobronchial and intrabronchial valve treatment that have been described by the currently published randomized controlled trials and other relevant papers regarding the complications and its management. In case there was no relevant literature regarding these subjects, recommendations are based on expert opinion. Complications include pneumothorax, post-obstruction pneumonia and hemoptysis. Also, the treatment may not be effective due to the presence of collateral ventilation or misplaced valves. Furthermore, an initial beneficial effect may vanish due to granulation tissue formation, valve dysfunction or valve migration. Careful follow-up after treatment with valves is important. Evaluation with a CT-scan and/or bronchoscopy is needed if there is no improvement after treatment, loss of benefit, or occurrence of important adverse events during follow-up. Expert opinion Treating severe emphysema patients with one-way valves requires continuous dedication and expertise, especially to achieve an optimal outcome and elegantly deal with the various complications after treatment.

The occurrence and progression of Parkinson's disease (PD) has been associated with the observation of elevated iron concentrations in the substantia nigra pars compacta (SNpc). While the reasons for the impact of elevated iron concentrations remain unclear, one hypothesis is that the presence of labile iron induces the oxidation of dopamine (DA) to toxic quinones such as aminochrome (DAC) and reactive oxygen species (ROS). As such, one of the proposed therapeutic strategies has been the use of iron chelators such as deferiprone (DFP) (which is recognized to have limitations related to its rapid degradation in the liver) to reduce the concentration of labile iron. In this study, a detailed investigation regarding the novel iron chelator, CN128, was conducted and a kinetic model developed to elucidate the fundamental behavior of this chelator. The results in this work reveal that CN128 is effective in alleviating the toxicity induced by iron and DA to neurons when DA is present at moderate concentrations. When all the iron is chelated by CN128, the formation of DAC and the oxidation of DA can be reduced to levels identical to that in the absence of iron. The production of H2O2 is lower than that generated via the autoxidation of the same amount of DA. However, when severe leakage of DA occurs, the application of CN128 is insufficient to alleviate the associated toxicity. This is attibuted to the less important role of iron in the production of toxic intermediates at high concentrations of DA. CN128 is superior to DFP with regard to the reduction in formation of DAC and elevation in DA concentration. In summary, the results of this study suggest that prodromal application of the chelator CN128 could be effective in preventing the onset and slowing the early stage development of PD symptoms associated with oxidants and toxic intermediates resulting from the iron-mediated oxidation of the neurotransmitter dopamine with CN128 likely to be superior to DFP in view of its greater in vivo availability and less problematic side effects.

STUDY DESIGN Retrospective database analysis. OBJECTIVE This study aimed to compare costs and complication rates following single-level lumbar decompression in patients under age 75 versus patients aged 75 and older. SUMMARY OF BACKGROUND DATA Lumbar decompression is a common surgical treatment for lumbar pathology; however, its effectiveness can be debated in elderly patients because complication rates and costs by age group are not well-defined. METHODS The Medicare database was queried through the PearlDiver server for patients who underwent single-level lumbar decompression without fusion as an index procedure. The 90-day complication and reoperation rates were compared between age groups after matching for sex and comorbidity burden. Same day and 90-day costs are compared. RESULTS The matched cohort included 89,388 total patients (n = 44,694 for each study arm). Compared to the under 75 age group, the 75 and older age group had greater rates of deep venous thrombosis (odds ratio [OR] 1.443, P = 0.042) and dural tear (OR 1.560, P = 0.043), and a lower rate of seroma complicating the procedure (OR 0.419, P = 0.009). There was no difference in overall 90-day reoperation rate in patients under age 75 versus patients aged 75 and older (9.66% vs. 9.28%, P = 0.051), although the 75 and older age group had a greater rate of laminectomy without discectomy (CPT-63047; OR 1.175, P

The recent discovery of magnetic nanoparticles (NPs) in human brain tissue has raised concerns regarding their source and neurotoxicity. As previous studies have suggested that magnetite in urban dust may be the source, we collected urban magnetic dust and thoroughly characterized the nature of ambient urban magnetic dust particles prior to investigating their neurotoxic potential. In addition to magnetite, magnetic dust contained an abundance (∼40%) of elemental iron (Fe0). The coexistence of magnetite and elemental iron was found in magnetic dust particles of inhalable (

Introduction: Treatment with AeriSeal is an alternate treatment option to achieve lung volume reduction in patients with severe COPD and emphysema who are not eligible for valve treatment. This study aimed to assess the safety and mode of action of a modified staged treatment algorithm with a staged treatment with lower dose of AeriSeal.Methods: We performed a prospective, multicenter feasibility study. AeriSeal was administered during two sequential bronchoscopies: 2 subsegments of a lobe treated with two 5 mL doses, followed by two 10 mL doses in a contralateral lobe after 6 weeks.Results: A total of 14 patients (36% male, mean FEV1 28.4% ± 6.7% of predicted) were enrolled. Ten patients completed both treatments, four were treated unilaterally. AeriSeal treatment resulted in significant TLVR (median 220.5 mL) at 3 months follow up. There were no significant changes from baseline at 12 months in lung function, exercise capacity and quality of life. During the 3-month post-treatment period, respiratory SAEs included 5 COPD exacerbations in 4 (28.6%) subjects, post-treatment acute inflammatory response (PAIR) in 2 (14.3%) subjects, and 1 respiratory failure event in 1 (7.1%) subject.Conclusion: The staged and lower dosed administration of AeriSeal does not impact the overall safety profile in terms of reducing the type and frequency of respiratory SAEs previously reported for a single-stage treatment. A larger volume of AeriSeal than used in this study may be necessary to provide meaningful clinical benefits.

IntroductionHand dexterity is the ability to execute the skilful movements using the hand and fingers. It is commonly impaired poststroke resulting in a profound deterioration in the quality of life for patients with stroke. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation, which has gained a popularity as an adjunct therapy in recovering motor dysfunction poststroke. Promising results have been gained from applying tDCS in combination with motor rehabilitation, however, the outcome of tDCS on the upper limb motor function poststroke has been varied. Different results are potentially related to the discrepancy of the area of brain stimulation. Therefore, we aim to enhance the application of tDCS to improve its effectiveness in recovering hand dexterity through testing our hypothesis that stimulating the primary motor cortex could improve fine dexterity more than gross dexterity.Methods and analysisThis protocol has been reported according to Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols guidelines. CENTRAL, MEDLINE, EMBASE, SCOPUS, Web of Science and CINAHL databases will be searched with no restriction in language and publication date. The selected studies will be randomised controlled trial investigating the effect of tDCS alone or in combination with motor rehabilitation in improving hand dexterity of patients with stroke with upper limb hemiparesis. The outcomes of interest are fine and gross hand dexterity measures. Two independent reviewers will assess the eligibility of the study, extract data and appraise the methodological quality. The data will be pooled in a meta-analysis if applicable or interpreted narratively. Grading of Recommendations, Assessment, Development and Evaluation approach will be used to assess the overall quality of evidence for the fine and gross dexterity measures.Ethics and disseminationEthical approval is not required for this study. The dissemination plan is to publish the results in a peer-review journal and presenting results in a conference.PROSPERO registration numberCRD42021262186.

This study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia. The study used data from the BC COVID-19 Cohort, which integrates data on all COVID-19 cases with data on hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia to 15 January 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance. Of the 56,874 COVID-19 cases included in the analysis, 2298 were hospitalized. Factors associated with increased hospitalization risk were as follows: male sex (adjusted risk ratio (aRR) = 1.27, 95%CI = 1.17–1.37), older age (p-trend &lt, 0.0001 across age groups increasing hospitalization risk with increasing age [aRR 30–39 years = 3.06, 95%CI = 2.32–4.03, to aRR 80+ years = 43.68, 95%CI = 33.41–57.10 compared to 20–29 years-old]), asthma (aRR = 1.15, 95%CI = 1.04–1.26), cancer (aRR = 1.19, 95%CI = 1.09–1.29), chronic kidney disease (aRR = 1.32, 95%CI = 1.19–1.47), diabetes (treated without insulin aRR = 1.13, 95%CI = 1.03–1.25, requiring insulin aRR = 5.05, 95%CI = 4.43–5.76), hypertension (aRR = 1.19, 95%CI = 1.08–1.31), injection drug use (aRR = 2.51, 95%CI = 2.14–2.95), intellectual and developmental disabilities (aRR = 1.67, 95%CI = 1.05–2.66), problematic alcohol use (aRR = 1.63, 95%CI = 1.43–1.85), immunosuppression (aRR = 1.29, 95%CI = 1.09–1.53), and schizophrenia and psychotic disorders (aRR = 1.49, 95%CI = 1.23–1.82). In an analysis restricted to women of reproductive age, pregnancy (aRR = 2.69, 95%CI = 1.42–5.07) was associated with increased risk of hospital admission. Older age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization.

To evaluate functional outcomes and survivorship in patients at 1 year after undergoing arthroscopic microfracture augmented with hyaline allograft for symptomatic chondral defects of the hip.Consecutive patients with and without prior hip procedures presenting with Outerbridge grade IV chondral lesion of the acetabulum or femoral head were prospectively followed. Patients underwent hip microfracture augmented with hyaline allograft suspended in autologous platelet-rich plasma between October 2016 and April 2018. Extent of cartilage degeneration was quantified using the chondromalacia severity index (CMI). Patient functional scores, including Tegner, Hip Outcome Score-Activities of Daily Living (HOS-ADL), Sport-Specific Subscale (HOS-SSS), modified Harris Hip Score (mHHS), and Nonarthritic Hip Score (NAHS) were collected preoperatively and at minimum 1-year postoperatively. Minimal clinically important difference (MCID) was analyzed. Statistical significance was established at P.05. Pearson's coefficient analysis was performed to identify preoperative variables correlated with clinical outcomes.Fifty-seven patients (86.4%) had minimum 1-year follow-up and were included in the final analysis, with a mean age and body mass index (BMI) of 38.3 ± 9.1 years and 27.7 ± 4.9 kg/mTreatment of hip chondral defects with microfracture and hyaline allograft augmentation demonstrated excellent survivorship and significantly improved patient report outcomes at 1 year.IV, retrospective case series.

Viral interferon (IFN) antagonist proteins mediate evasion of IFN-mediated innate immunity and are often multifunctional, with distinct roles in viral replication. The Ebola virus IFN antagonist VP24 mediates nucleocapsid assembly, and inhibits IFN-activated signaling by preventing nuclear import of STAT1 via competitive binding to nuclear import receptors (karyopherins). Proteins of many viruses, including viruses with cytoplasmic replication cycles, interact with nuclear trafficking machinery to undergo nucleocytoplasmic transport, with key roles in pathogenesis; however, despite established karyopherin interaction, potential nuclear trafficking of VP24 has not been investigated. We find that inhibition of nuclear export pathways or overexpression of VP24-binding karyopherin results in nuclear localization of VP24. Molecular mapping indicates that cytoplasmic localization of VP24 depends on a CRM1-dependent nuclear export sequence at the VP24 C-terminus. Nuclear export is not required for STAT1 antagonism, consistent with competitive karyopherin binding being the principal antagonistic mechanism, while export mediates return of nuclear VP24 to the cytoplasm where replication/nucleocapsid assembly occurs.

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19) resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%) which associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19, demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney., Graphical abstract

Background: Absence of interlobar collateral ventilation is essential to achieve lobar volume reduction after endobronchial valve (EBV) treatment and can be assessed using the Chartis measurement. However, especially in lower lobe measurements, Chartis can be complicated by the “no-flow phenomenon”, during which a sudden cessation of flow is observed, leading to an unreliable measurement. If this phenomenon occurs in the right lower lobe, when measuring collateral flow over the right major fissure, the entrance to the right middle lobe should be occluded, and the Chartis balloon should be placed in the right upper lobe. Both Watanabe spigots and balloon catheters can be used to achieve occlusion. Objective: Our aim was to demonstrate that right middle lobe occlusion with a blocking device is helpful in obtaining a reliable Chartis outcome in case of the no-flow phenomenon in the right lower lobe. Methods: We performed a retrospective analysis of patients scheduled for EBV treatment in an EBV registry between September 2016 and September 2019. Results: We included 15 patients with severe emphysema (median age 63 years [range 47–73], 73% female, and FEV1 24% [range 19–36] of predicted), who required temporary middle lobe occlusion (12 Watanabe spigot, 3 balloon catheter). After occlusion, a reliable Chartis outcome was obtained in all patients. Conclusion: Temporary middle lobe occlusion using a blocking device is helpful in obtaining a reliable Chartis outcome in case of a right lower lobe no-flow phenomenon.

Background: Bronchoscopic lung volume reduction using the Zephyr® endobronchial valve (EBV) is a guideline treatment for patients with advanced emphysema. To achieve volume reduction, it is crucial that there is absence of collateral ventilation and a complete occlusion of the target lobe. While 3 EBV sizes (4.0; 4.0-LP; and 5.5) are currently available to accommodate all airway sizes, local anatomical variations sometimes warrant a valve with a wide diameter but shorter length. To address this, a new “low profile” 5.5-LP EBV has been introduced. Objective: In this study, we evaluated the feasibility, safety, and efficacy of this new 5.5-LP EBV. Methods: This was a single-center, prospective, open-label study. Patients were included if eligible for valve treatment with a local anatomy suitable to place at least one 5.5-LP EBV. Feasibility of placement of the 5.5-LP EBV was reported. Safety, CT parameters, pulmonary function tests, and St. George’s Respiratory Questionnaire (SGRQ) were assessed at baseline and 6 weeks after treatment. Results: We included 30 patients with severe chronic obstructive pulmonary disease (forced expiratory volume in 1 s [FEV1] 29 ± 10%; [RV] 242 ± 46%; and SGRQ 56 ± 11 points). Besides the regular EBV sizes, a median of 1 (1–3) of the new 5.5-LP EBV was placed. No valve adjustment was needed during the initial procedure. A single asymptomatic small pneumothorax was observed in 1 patient. In 4 patients, a revision bronchoscopy was performed due to absence of clinical benefit. In 1 patient, this was related to a dislocation of the 5.5-LP EBV. Clinically relevant improvements were seen in target lobar volume reduction (–1,554 mL), FEV1 +39%, RV –960 mL, and SGRQ –18 points. Conclusions: In this first in human study, the 5.5-LP EBV could be placed into wide segments with a shorter landing length without unexpected complications and with good efficacy outcomes.

Background Prostate cancer (PCa) is a largely prevalent disease in the United States. Moreover, it is unclear whether the thromboembolic burden of disease remains present after the cancer has been treated and whether such state impacts the short-term outcomes of orthopedic procedures. Therefore, the purpose of this study is to assess 90-day postoperative complications and costs after total hip arthroplasty (THA) for osteoarthritis in patients with a history of PCa. Methods Two groups of patients who underwent THA for osteoarthritis in the Medicare Standard Analytical Files were identified through the PearlDiver server. Both groups were matched based on age, diabetes, smoking status, chronic kidney disease, alcohol abuse, chronic liver disease, and obesity in order to create a case-control study comparison. The 90-day complication rates after THA were compared using univariate regressions (odds ratio). We hypothesized that patients with a history of PCa would develop increased rates of thromboembolic complications based on a prolonged procoagulative state. Results After matching, each group was comprised of 62,571 patients. Our findings identified greater 90-day pneumonia rates for those without a history of PCa (3.26% vs 2.68%; odds ratio, 0.82). All other complications including thromboembolic diseases were clinically comparable in both groups during the 90-day postoperative period. The charges and reimbursements for the 90-day period were also comparable. Conclusion In our large case-control study of 125,142 patients, we found that patients with a history of PCa do not have increased risk of short-term complications after THA and that the mean 90-day reimbursements were similar for both groups at $14,153 for PCa patients and $14,033 for those without (P = .114).

Over the past 20 years, and particularly in the last decade, significant developmental milestones have driven basic, translational, and clinical advances in the field of stem cell and regenerative medicine. In this article, we provide a systemic overview of the major recent discoveries in this exciting and rapidly developing field. We begin by discussing experimental advances in the generation and differentiation of pluripotent stem cells (PSCs), next moving to the maintenance of stem cells in different culture types, and finishing with a discussion of three-dimensional (3D) cell technology and future stem cell applications. Specifically, we highlight the following crucial domains: 1) sources of pluripotent cells; 2) next-generation in vivo direct reprogramming technology; 3) cell types derived from PSCs and the influence of genetic memory; 4) induction of pluripotency with genomic modifications; 5) construction of vectors with reprogramming factor combinations; 6) enhancing pluripotency with small molecules and genetic signaling pathways; 7) induction of cell reprogramming by RNA signaling; 8) induction and enhancement of pluripotency with chemicals; 9) maintenance of pluripotency and genomic stability in induced pluripotent stem cells (iPSCs); 10) feeder-free and xenon-free culture environments; 11) biomaterial applications in stem cell biology; 12) three-dimensional (3D) cell technology; 13) 3D bioprinting; 14) downstream stem cell applications; and 15) current ethical issues in stem cell and regenerative medicine. This review, encompassing the fundamental concepts of regenerative medicine, is intended to provide a comprehensive portrait of important progress in stem cell research and development. Innovative technologies and real-world applications are emphasized for readers interested in the exciting, promising, and challenging field of stem cells and those seeking guidance in planning future research direction.

The aim of this study was to assess (1) temporal trends, (2) primary indication, (3) patient-level demographics (age, race, gender, health status, and median income quartile), and (4) region and hospital type for all patients receiving primary total knee arthroplasty (TKA) between 2009 and the third quarter of 2015. The National Inpatient Sample Database (NIS) was used to identify all patients who underwent a TKA between 2009 and the third quarter of 2015. Regression analysis was utilized to assess trends. Chi-square analysis was used to explore categorical variables whereas Kruskal–Wallis test was used to explore nonparametric continuous variables. TKA utilization increased between 2009 and 2015 with the highest volume occurring during the fall. Primary osteoarthritis was the primary indication in 98% of cases. There was an increase in minority representation among recipients. Black TKA recipients were younger and had lower median age-adjusted Charlson's comorbidity index (CCI). Black recipients were most likely to be of the lowest 25% of median income than any other races. The Midwest demonstrated the greatest increase in TKAs performed per 100,000 between 2009 and 2014. Case volumes shifted to urban teaching hospitals between 2009 and 2014. There were differences in age of presentation, preoperative morbidity, and income status among races. Furthermore, our findings revealed a more rapid growth in TKA procedures per 100,000 in the Midwest, in addition to volume shifts toward urban teaching hospitals. Future studies are needed to update our findings as well as explore trends in racial disparities for primary TKA recipients.

Background: Heterotopic ossification (HO) is abnormal growth of ectopic bone and negatively affects the outcomes after total knee arthroplasty (TKA). This systematic review and meta-analysis were performed to characterize the prevalence and severity of HO after primary TKA. Methods: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Patient demographics, publication year, and HO prevalence after a primary TKA were recorded. A meta-analysis was performed to determine the overall prevalence of HO formation, and a subanalysis compared the studies published in different timeframes to determine whether a temporal effect exists for HO prevalence. Results: Two thousand nine hundred eighty-eight patients underwent primary TKA across the included studies. Fourteen percent of patients (9% to 20%; I2: 93.68%) developed HO postoperatively during a mean follow-up of 40.1 months (11 to 108 months). HO rates seemed to decrease in studies published in more recent years, with a pooled HO prevalence of 5% (0% to 13%; I2: 92.26%) among studies published in the past 15 years compared with 18% (12% to 25%; I2: 92.49%) among studies published before then. Conclusion: Although studies reported a relatively low overall rate of HO after a primary TKA, the absence of a single, standardized classification system precludes the comparisons of HO severity between studies. Overall, HO prevalence seems to have decreased over time, likely reflecting the changes in perioperative medication protocols.

Background Membranous lupus nephritis (MLN) comprises 10%–15% of lupus nephritis and increases morbidity and mortality of patients with SLE through complications of nephrotic syndrome and chronic kidney failure. Identification of the target antigens in MLN may enable noninvasive monitoring of disease activity, inform treatment decisions, and aid in prognostication, as is now possible for idiopathic MN caused by antibodies against the phospholipase A2 receptor. Here, we show evidence for type III TGF-β receptor (TGFBR3) as a novel biomarker expressed in a subset of patients with MLN. Methods Mass spectrometry was used for protein discovery through enrichment of glomerular proteins by laser capture microdissection and through elution of immune complexes within MLN biopsy specimens. Colocalization with IgG within glomerular immune deposits from patients and disease controls was evaluated by confocal microscopy. Immunostaining of consecutive case series was used to determine the overall frequency in MN and MLN. Results TGFBR3 was found to be enriched in glomeruli and coimmunoprecipitated with IgG within a subset of MLN biopsy specimens by mass spectrometry. Staining of consecutive MN cases without clinical evidence of SLE did not show TGFBR3 expression (zero of 104), but showed a 6% prevalence in MLN (11 of 199 cases). TGFBR3 colocalized with IgG along the glomerular basement membranes in TGFBR3-associated MN, but not in controls. Conclusions Positive staining for TGFBR3 within glomerular immune deposits represents a distinct form of MN, substantially enriched in MLN. A diagnosis of TGFBR3-associated MN can alert the clinician to search for an underlying autoimmune disease.

We aimed to investigate a sexually dimorphic role of calcitonin gene-related peptide (CGRP) in rodent models of pain. Based on findings in migraine where CGRP has a preferential pain-promoting effect in female rodents, we hypothesized that CGRP antagonists and antibodies would attenuate pain sensitization more efficaciously in female than male mice and rats. In hyperalgesic priming induced by activation of interleukin 6 signaling, CGRP receptor antagonists olcegepant and CGRP8-37both given intrathecally, blocked, and reversed hyperalgesic priming only in females. A monoclonal antibody against CGRP, given systemically, blocked priming specifically in female rodents but failed to reverse it. In the spared nerve injury model, there was a transient effect of both CGRP antagonists, given intrathecally, on mechanical hypersensitivity in female mice only. Consistent with these findings, intrathecally applied CGRP caused a long-lasting, dose-dependent mechanical hypersensitivity in female mice but more transient effects in males. This CGRP-induced mechanical hypersensitivity was reversed by olcegepant and the KCC2 enhancer CLP257, suggesting a role for anionic plasticity in the dorsal horn in the pain-promoting effects of CGRP in females. In spinal dorsal horn slices, CGRP shifted GABAAreversal potentials to significantly more positive values, but, again, only in female mice. Therefore, CGRP may regulate KCC2 expression and/or activity downstream of CGRP receptors specifically in females. However, KCC2 hypofunction promotes mechanical pain hypersensitivity in both sexes because CLP257 alleviated hyperalgesic priming in male and female mice. We conclude that CGRP promotes pain plasticity in female rodents but has a limited impact in males.SIGNIFICANCE STATEMENTThe majority of patients impacted by chronic pain are women. Mechanistic studies in rodents are creating a clear picture that molecular events promoting chronic pain are different in male and female animals. We sought to build on evidence showing that CGRP is a more potent and efficacious promoter of headache in female than in male rodents. To test this, we used hyperalgesic priming and the spared nerve injury neuropathic pain models in mice. Our findings show a clear sex dimorphism wherein CGRP promotes pain in female but not male mice, likely via a centrally mediated mechanism of action. Our work suggests that CGRP receptor antagonists could be tested for efficacy in women for a broader variety of pain conditions.

Many viruses target signal transducers and activators of transcription (STAT) 1 and 2 to antagonise antiviral interferon signalling, but targeting of signalling by other STATs/cytokines, including STAT3/interleukin 6 that regulate processes important to Ebola virus (EBOV) haemorrhagic fever, is poorly defined. We report that EBOV potently inhibits STAT3 responses to interleukin-6 family cytokines, and that this is mediated by the interferon-antagonist VP24. Mechanistic analysis indicates that VP24 effects a unique strategy combining distinct karyopherin-dependent and karyopherin-independent mechanisms to antagonise STAT3-STAT1 heterodimers and STAT3 homodimers, respectively. This appears to reflect distinct mechanisms of nuclear trafficking of the STAT3 complexes, revealed for the first time by our analysis of VP24 function. These findings are consistent with major roles for global inhibition of STAT3 signalling in EBOV infection, and provide new insights into the molecular mechanisms of STAT3 nuclear trafficking, significant to pathogen-host interactions, cell physiology and pathologies such as cancer., Author summary Ebola virus (EBOV) continues to pose a significant risk to human health globally, causing ongoing disease outbreaks with case-fatality rates between 40 and 65%. Suppression of immune responses is a critical component of EBOV haemorrhagic fever, but understanding of EBOV impact on signalling by cytokines other than interferon is limited. We find that infectious EBOV inhibits interleukin-6 cytokine signalling via antagonism of STAT3. The antagonistic strategy uniquely combines two distinct mechanisms, which appear to reflect differing nuclear trafficking mechanisms of critical STAT3 complexes. This provides fundamental insights into the mechanisms of pathogenesis of a lethal virus, and biology of STAT3, a critical player in immunity, development, growth and cancer.

Optic pathway glioma (OPG) is a classic complication of neurofibromatosis type 1 (NF1) and can impair visual function in children with this condition. The objective of this study is to describe clinical, paraclinical and prognostic characteristics of OPG associated with NF1.In this retrospective observational study of children followed for OPG associated with NF1 in a University Hospital, we analyzed the ophthalmological examination, brain and orbital imaging, management and the presence of associated endocrinopathy.We examined 114 children with NF1, of which 26 (22.81%) presented with OPG. Mean ages at diagnosis of NF1 and OPG were 3.83 years and 6.23 years, respectively. Mean visual acuity was 20/24.4 for the worse eye and 20/23.1 for the better eye. The RNFL (retinal nerve fiber layer) was thinner in subjects than in age-matched controls (p0.0001). Retrochiasmal location of the OPG (DodgeC) was associated with lower binocular visual acuity than other locations and20/32 (p=0.028); 28.03% of OPG (5 girls and 1 boy) were treated with chemotherapy, and the others were monitored; 19.23% had an associated endocrinopathy.OPG complicates 22.81% of NF1 cases in our series. Our study shows that retrochiasmal location of the glioma and female sex are poor prognostic factors. It also highlights the important role of OCT, since a decrease in RNFL is statistically associated with the presence of an OPG.

Background Periprosthetic joint infection (PJI) remains a rare, yet devastating complication of total joint arthroplasty (TJA). Chronic infection is generally considered a contraindication to debridement, antibiotics, and implant retention (DAIR); however, outcomes stratified by chronicity have not been well documented. Methods A retrospective review of all DAIR cases performed at a single institution from 2008 to 2015 was performed. Chronicity of PJI was categorized as acute postoperative, chronic, or acute hematogenous. Failure after DAIR, defined as re-revision for infection recurrence with the same organism, was evaluated between the 3 chronicity groups at 90 days as well as at a minimum 2-year follow-up. Results Overall, 248 patients undergoing DAIR for total hip arthroplasty or total knee arthroplasty PJI were included. Categorization of PJI was acute (acute postoperative) in 59 cases (24%), chronic in 54 (22%), and acute hematogenous in 135 (54%). DAIR survivorship was 47% (range 0.3-10 years). Overall, there were 118 (47.6%) treatment failures after DAIR with a minimum of 2-year follow-up. There was no difference in failure rate between total hip or total knee arthroplasty patients (P = .07). Patients infected with Staphylococcus conferred a higher risk of failure for all DAIR procedures regardless of chronicity category. Conclusion Identification of microbial species prior to undertaking DAIR may be more clinically relevant than stratification according to chronicity category when considering treatment options.

Background: Repetitive throwing in baseball pitchers can lead to pathologic changes in shoulder anatomy, range of motion (notably glenohumeral internal rotation deficit), and subsequent injury; however, the ideal strengthening, recovery, and maintenance protocol of the throwing shoulder in baseball remains unclear. Two strategies for throwing shoulder recovery from pitching are straight-line long-toss (SLT) throwing and ultra-long-toss (ULT) throwing, although neither is preferentially supported by empirical data. Hypothesis: ULT will be more effective in returning baseline internal rotation as compared with SLT in collegiate pitchers after a pitching session. Study Design: Cohort study. Level of Evidence: Level 3. Methods: A total of 24 National Collegiate Athletic Association Division I baseball pitchers with mean age 20.0 ± 1.1 years were randomized to either the ULT group (n = 13; 9 right-hand dominant, 4 left-hand dominant) or SLT group (n = 11; 10 right-hand dominant, 1 left-hand dominant). Measurements (dominant and nondominant, 90° abducted external rotation [ER], internal rotation [IR], and total range of motion [TROM]) were taken at 5 time points across 3 days: before and immediately after a standardized bullpen session on day 1; before and immediately after a randomized standardized ULT or SLT session on day 2; and before practice on Day 3. Results: ULT demonstrated significantly greater final ER compared with baseline (+10°; P = 0.05), but did not demonstrate significant IR changes. Similarly, SLT demonstrated significantly greater post-SLT ER (+12°; P = 0.02) and TROM (+12°; P = 0.01) compared with baseline, but no significant IR changes. Final ER measurements were similar between ULT (135° ± 14°) and SLT (138° ± 10°) ( P = 0.59). There was also no statistically significant difference in final IR between ULT (51° ± 14°) and SLT (56° ± 8°) ( P = 0.27). Conclusion: The routine use of postperformance, ULT throwing to recover from range of motion alterations, specifically IR loss, after a pitching session is not superior to standard, SLT throwing. Based on these findings, the choice of postpitching recovery throwing could be player specific based on experience and comfort. Clinical Relevance: The most effective throwing regimens for enhancing performance and reducing residual impairment are unclear, and ideal recovery and maintenance protocols are frequently debated with little supporting data. Two strategies for throwing shoulder recovery from pitching are SLT and ULT throwing. These are employed to help maintain range of motion and limit IR loss in pitchers. The routine use of ULT throwing for recovery and to limit range of motion alterations after a pitching session is not superior to SLT throwing.

Causal factors underlying coal workers' pneumoconiosis (CWP) have been variously attributed to the presence of carbon, crystalline silica and reduced iron (Fe) minerals, especially pyrite and Fe/Si-amorphous compounds. The aim of this research was to assess the role of iron in CWP and, more specifically, the cytotoxicity of coal dusts with different elemental composition towards alveolar macrophages (AMs). Survival rate of AMs, alteration in the production of pro-inflammatory cytokine TNF-α, MDA (the lipid peroxidation product) and intracellular GSH were assessed using commercial assay kits. The quantitative interaction between iron and GSH was investigated by developing a numerical model. The presence of various reduced Fe minerals (viz. pyrite and siderite) in coal dusts exhibited a consistently acute adverse impact on the viability of AMs and enhanced the production of TNF-α. The presence of the clinically available Fe chelator deferiprone (DFP) and the cytosolic antioxidant glutathione (GSH) significantly increased the viability of AMs exposed to Fe bearing coal dusts, suggesting coal dusts containing reduced Fe minerals were likely contributors to the initial stages of AM cytotoxicity via a ferroptosis related pathway. Chemical kinetic modeling indicated that these results may be attributed to an enhanced consumption of GSH as a result of Fe redox cycling. Fe

Goal of the study was to determine the average noise exposure to the orthopaedic surgeon performing hip and knee arthroplasty and the benefit of customized hearing protection. Data from dosimeters (3MTM Edge 4) worn by three adult reconstruction orthopedic surgeons for a total of 27 operative day recordings was analyzed using 3MTM Detection Management Software (product version 2.7.152.0). Westone TRU custom hearing protection was used with different filters according to noise reduction rating (NRR). The overall average decibel level was 80.64 dB (73.6-87.2 dB, +/- 4.18). The peak decibel level averaged 103.66 dB (97.30-110.30, +/-3.02). The authors subjective trial of custom hearing protection determined the NRR 10 and 15 filters were most effective at noise reduction with adequate ability to communicate effectively. Our study demonstrates that the daily exposure to the total joint surgeon exceeds safe levels. (Journal of Surgical Orthopaedic Advances 29(4):202-204, 2020).

Case A 69-year-old woman underwent revision total knee arthroplasty for patellar component aseptic loosening. The periprosthetic tissue demonstrated histologic features of an adaptive immune response (aseptic lymphocyte-dominant vasculitis-associated lesion [ALVAL]). No particles of corrosion debris were identified. The inflammation seemed to be associated with zirconium oxide (ZrO2) particles added as a bone cement radio-opacifier. Conclusion The factors responsible for the adaptive immune response cannot be determined with certainty; however, this is the first reported case of ALVAL associated with ZrO2-containing bone cement. Previous reports describing ALVAL around failed total knee prostheses have not included observations about the type of contrast material added to cement.

Background The incidence of heterotopic ossification (HO) after total knee arthroplasty (TKA) varies and is of unclear clinical significance. This study aimed to identify the incidence of HO in patients undergoing revision TKA for either stiffness or aseptic loosening/instability and determine if the presence of HO is associated with inferior absolute range of motion (ROM) and ROM gains. Methods Eighty-seven patients were prospectively enrolled and separated into 2 cohorts to evaluate ROM after revision TKA (2017-2019). Group 1 (N = 40) patients were revised for stiffness, while group 2 (N = 47) patients were revised for either aseptic loosening or instability. Goniometer-measured ROM values were obtained preoperatively and at 6 weeks, 6 months, and 1 year postoperatively. Statistical analysis included a Fisher’s exact test to assess for an association between preoperative HO and final ROM at 1 year after revision TKA. Results HO was identified on preoperative radiographs in 17 patients (20%). There was a significantly higher rate of preoperative HO in patients revised for stiffness compared to patients revised for instability or loosening (30% vs 11%; P = .03). Five cases of HO qualitatively identified as most clinically severe were associated with lower ROM at each time point compared to the remainder of HO cases in this study cohort (P Conclusion The presence of HO is greater in patients undergoing revision TKA for stiffness. Additionally, HO severity appears to have a major effect on preoperative and postoperative ROM trajectory. This information should help guide patient expectations and highlight the need for a comprehensive, standardized classification system for HO.

Summary Introduction Optic Nerve Head Drusen (ONHD) are very rare among black patients but may cause more severe visual defects in these patients. The goal of our study was to describe the frequency of visual field defects secondary to OND in Afro-Caribbean patients and study the characteristics of their physical examination, color vision and contrast sensitivity. Methods We carried out a prospective study at the Martinique university medical center on patients of African descent with ONHD diagnosed on fundus examination and B-scan ultrasonography. All patients received a complete neuro-ophthalmological examination. The primary study endpoint was the frequency of visual field defects. Secondary study endpoints were the results of ETDRS visual acuity, Pelli-Robson contrast sensitivity chart, and 15 hue color vision test. Results Sixteen eyes of 10 patients from 11 to 68 years of age were included. Forteen eyes (87%) had exposed ONHD. Eleven eyes (69%) showed a visual field defect: 9 eyes (69%) had an enlarged blind spot, and 9 eyes (69%) had an arcuate scotoma. 3 eyes (19%) had loss of ETDRS visual acuity, and 12 eyes (75%) showed loss of Pelli-Robson contrast sensitivity. Five eyes (31%) had an abnormal color vision test. Conclusion This is one of the largest case series of ONHD in Black patients. The frequency of visual field defects was high but comparable to that of studies in other ethnic groups. Larger comparative studies are necessary to confirm these results.