Marjolin\u27s Tumor Complicating Chronic Periprosthetic Infection of a Total Knee Arthroplasty

Marjolin\u27s tumor is a term used to describe a malignancy developing in the setting of a chronic wound, infection, or other tissue subject to chronic inflammatory changes. These malignancies usually present after many years of chronicity, and can range from lower grade basal cell carcinomas to high-grade sarcomas. We present the case of a squamous cell carcinoma that developed within a chronic periprosthetic infection of a total knee arthroplasty of 7 years duration. The intra-articular location, association with an orthopaedic implant, and brief latency period are all unique features of this case

Telemedicine Evaluations in Neuro-Ophthalmology During the COVID19 Pandemic: Patient and Physician Surveys

Background: The novel coronavirus 2019 (COVID-19) pandemic has transformed healthcare. With the need to limit COVID-19 exposures, telemedicine has become an increasingly important format for clinical care. Compared to other fields, neuro-ophthalmology faces unique challenges given its dependence on physical examination signs that are difficult to elicit outside the office setting. As such, it is imperative to understand both patient and provider experiences in order to continue to adapt the technology and tailor its application. The purpose of this study is to analyze both neuro-ophthalmology physician and patient satisfaction with virtual health visits during the time of the COVID-19 pandemic. Methods: Across three institutions (NYU Langone Health, Indiana University Health, and Columbia University Medical Center), telemedicine surveys were administered to 159 patients. Neuro-ophthalmologists completed 157 surveys; each of these were linked to a single patient visit. Patient surveys consisted of five questions regarding visit preparation, satisfaction, challenges, and comfort. The physician survey included four questions that focused on ability to gather specific clinical information by history and examination. Results: Among 159 patients, 104 (65.4%) reported that they were satisfied with the visit, and 149 (93.7%) indicated that they were comfortable asking questions. Sixty-eight (73.9%) patients found the instructions provided prior to the visit easy to understand. Potential areas for improvement noted by patients included more detailed preparation instructions and better technology (phone positioning, internet connection, software). Over 87% (137/157) of neuroophthalmologists surveyed reported having performed an examination that provided enough information for medical decision-making. Some areas of the neuro-ophthalmologic exam were reported to be easy to conduct (range of eye movements, visual acuity, Amsler grids, Ishihara color plates, and pupillary exam). Other components were more difficult (saccades, red desaturation, visual fields, convergence, oscillations, ocular alignment, and smooth pursuit); some were especially challenging (vestibulo-ocular reflex [VOR], VOR suppression, and optokinetic nystagmus). Clinicians noted that virtual health visits were limited by patient preparation, inability to perform certain parts of the examination (funduscopy and pupils), and technological issues. Conclusions: Among virtual neuro-ophthalmology visits evaluated, most offer patients with appointments that satisfy their needs. The majority of physicians in this cohort obtained adequate clinical information for decision-making. Even better technology and instructions may help improve aspects of virtual health visits

Plasmodium knowlesi: Reservoir Hosts and Tracking the Emergence in Humans and Macaques

Plasmodium knowlesi, a malaria parasite originally thought to be restricted to macaques in Southeast Asia, has recently been recognized as a significant cause of human malaria. Unlike the benign and morphologically similar P. malariae, these parasites can lead to fatal infections. Malaria parasites, including P. knowlesi, have not yet been detected in macaques of the Kapit Division of Malaysian Borneo, where the majority of human knowlesi malaria cases have been reported. In order to extend our understanding of the epidemiology and evolutionary history of P. knowlesi, we examined 108 wild macaques for malaria parasites and sequenced the circumsporozoite protein (csp) gene and mitochondrial (mt) DNA of P. knowlesi isolates derived from macaques and humans. We detected five species of Plasmodium (P. knowlesi, P. inui, P. cynomolgi, P. fieldi and P. coatneyi) in the long-tailed and pig-tailed macaques, and an extremely high prevalence of P. inui and P. knowlesi. Macaques had a higher number of P. knowlesi genotypes per infection than humans, and some diverse alleles of the P. knowlesi csp gene and certain mtDNA haplotypes were shared between both hosts. Analyses of DNA sequence data indicate that there are no mtDNA lineages associated exclusively with either host. Furthermore, our analyses of the mtDNA data reveal that P. knowlesi is derived from an ancestral parasite population that existed prior to human settlement in Southeast Asia, and underwent significant population expansion approximately 30,000–40,000 years ago. Our results indicate that human infections with P. knowlesi are not newly emergent in Southeast Asia and that knowlesi malaria is primarily a zoonosis with wild macaques as the reservoir hosts. However, ongoing ecological changes resulting from deforestation, with an associated increase in the human population, could enable this pathogenic species of Plasmodium to switch to humans as the preferred host

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: Prespecified analyses from the REVIVED-BCIS2 trial

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82–1.30]; P =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920048

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Functional Outcome of Above-Knee Amputation After Infected Total Knee Arthroplasty

Background: Periprosthetic joint infection is a serious complication of total knee arthroplasty (TKA). Management usually involves irrigation and debridement, polyethylene liner exchange, one-stage revision, two-stage revision, knee arthrodesis, or ultimately above-knee amputation (AKA). We present our experience with 21 patients who underwent AKA as a sequela of unresolved infected TKA, highlighting their etiology and functional outcomes. Methods: A retrospective chart review was performed for all cases of infected TKA treated with AKA at 1 institute from January 2007 to December 2020, with a minimum follow-up of 1 year. Patient demographics, Charlson comorbidity index, culture results, ambulation status, prosthesis fitting, and functional outcomes were collected. Short Form-36 and activities of daily living questionnaires were used for functional outcome assessment. Results: Twenty-one patients were identified, 7 of whom were male (33.3%). Mean ± standard deviation follow-up was 5.7 ± 3.1 years (range, 1-11 years). Mean ± standard deviation age was 57.9 ± 10.7 years (range, 38-87 years), and the mean body mass index was 33.5 ± 6.4 kg/m2 (range, 25.4-46 kg/m2). Gram-positive organisms were identified in 15 cases (66.7%). Prosthesis fitting was successful in 17 patients (81%). Post-AKA ambulation was achieved in 12 patients (57.1%). The ambulating group showed higher Short Form-36 and activities of daily living scores when compared with patients who did not ambulate (60.2 vs 43.3, P = .041, and 67.2 vs 52.7, P = .029, respectively). Conclusions: AKA should be considered solely as the final recourse for infected TKA. Despite the low-to-moderate patient-reported postoperative outcomes, prosthesis fitting and maintaining ambulation can improve postoperative functional outcomes

Tobramycin Blood Levels after Local Antibiotic Treatment of Bone and Soft Tissue Infection

Local antibiotic delivery using different carriers plays an important role in both infection prophylaxis and treatment. Besides dead space management, these carriers have the advantage of providing a high concentration of local antibiotics with a lower risk of systemic toxicity. Few studies have reported on systemic toxicity associated with antibiotic-impregnated carriers. The present study investigates the systemic tobramycin concentration at 24, 48 and 72 h postoperatively after using tobramycin-loaded polymethyl methacrylate (PMMA) and calcium sulfate (CS) as local antibiotic carriers. Additionally, this work assesses the renal function postoperatively for indications of acute kidney injury (AKI). Fifty-two patients were treated in 58 procedures with tobramycin and vancomycin-loaded PMMA, CS, or both. All systemic tobramycin levels were <2 mcg/mL at 72 h, and the resulting rate of AKI was 12% (7/58). In conclusion, local tobramycin antibiotic delivery using PMMA, CS, or both remains a safe and effective modality in the treatment of osteomyelitis as long as the surgeon is aware of its possible nephrotoxic effect