I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations.

INTRODUCTION: The COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalised with severe COVID-19. The Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (ISPY COVID-19 trial) was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation and challenges of the ISPY COVID-19 trial during the first phase of trial activity from April 2020 until December 2021. METHODS AND ANALYSIS: The ISPY COVID-19 Trial is a multicentre open-label phase 2 platform trial in the USA designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID-19 Trial network includes academic and community hospitals with significant geographical diversity across the country. Enrolled patients are randomised to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes-time to recovery and mortality. The statistical design uses a Bayesian model with 'stopping' and 'graduation' criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrols to a maximum of 125 patients per arm and is compared with concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrolment and adaptation of the trial design are ongoing. ETHICS AND DISSEMINATION: ISPY COVID-19 operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT04488081.

Evaluation of a New Bone Conduction Device for the Rehabilitation of Single-Sided Deafness: Effects on Speech Understanding in Noise.

INTRODUCTION: A new external, adhesive, no-pressure bone-conduction device provides rehabilitation for conductive hearing loss and single-sided deafness (SSD). The purpose of the study is to evaluate speech recognition performance with the bone-conduction contralateral routing of signal (aBC-CROS) and compare it to an air-conduction CROS (AC-CROS) used by subjects for at least 1 year. METHODS: Ten SSD patients underwent speech understanding in noise tests with their AC-CROS, the aBC-CROS, and unaided. The 1st test session took place the day the aBC-CROS was fitted, with the second session after 2 weeks of aBC-CROS use. Two configurations were used: speech presented on the deaf side and noise on the normal side and the reverse. RESULTS: The speech recognition threshold (SRT) improved with both devices when speech was presented to the deaf side. Nine patients showed significant improvement (p < 0.016) with the AC-CROS (mean: 2.8 dB) and the aBC-CROS (mean: 3.0 dB). Mean difference of improvement was significant between unaided and aBC-CROS (p = 0.001) or AC-CROS (p = 0.006). The SRT deteriorated by an average of 2.3 dB with the AC-CROS with noise presented on the deaf side, with significance found for six patients (p < 0.016). The aBC-CROS did not affect performance in this configuration (mean improvement: 0.3 dB) and only one patient had a significant SRT degradation (p < 0.016). Mean difference of improvement was significant between the AC-CROS and aBC-CROS (p = 0.021) or unaided (p = 0.05). DISCUSSION: The aBC-CROS is a good alternative to the existing CROS devices for SSD rehabilitation, as it offers the same benefit with none of the drawbacks when noise is on the patient's deaf side.

Recurrent Lymphocytic Pleural Effusion as a Complication of Ventriculopleural Shunt Meningitis Caused by Cutibacterium Acnes.

Cutibacterium acnes (C. acnes) is part of the normal flora and has been linked to many invasive and pleural infections. Though it is usually considered a contaminant bacterium, full antimicrobial therapy might result in the resolution of foreign body-related infections. In this report, we describe an infection that started as ventriculopleural shunt meningitis but was complicated by a recurrent lymphocytic pleural infection. Ultimately, there was a resolution of pleural effusions after treatment of C. acnes.

Cutibacterium acnes Pneumonia in an Immunocompromised Patient: A Case Report and Review of the Literature.

Cutibacterium acnes (C. acnes), known previously as Proprionebacterium acnes, is a common skin and mucous membrane colonizing bacteria. On rare occasions it has been associated with invasive infections in both immunocompetent and immunosuppressed patients. We describe the case of a 55-year-old female with a history of Sjogren's syndrome and psoriatic arthritis on TNF-alpha inhibitor therapy with etanercept. She presented with signs and symptoms of a thoracic infection with pulmonary nodules, hilar adenopathy, and bronchiectasis on thoracic computed tomography. She was diagnosed with C. acnes pneumonia based on culture growth from both endoscopic bronchial ultrasound transbronchial lymph node needle biopsy and navigational bronchoscopy transbronchial lung biopsy. Our patient noticed marked symptom relief and radiographic pulmonary parenchymal improvement with intravenous ceftriaxone provided for a six-week course. This case highlights the potential invasive disease caused by C. acnes, a common skin commensal.

M2M Communication Assessment in Energy-Harvesting and Wake-Up Radio Assisted Scenarios Using Practical Components.

Techniques for wireless energy harvesting (WEH) are emerging as a fascinating set of solutions to extend the lifetime of energy-constrained wireless networks, and are commonly regarded as a key functional technique for almost perpetual communications. For example, with WEH technology, wireless devices are able to harvest energy from different light sources or Radio Frequency (RF) signals broadcast by ambient or dedicated wireless transmitters to support their operation and communications capabilities. WEH technology will have increasingly wider range of use in upcoming applications such as wireless sensor networks, Machine-to-Machine (M2M) communications, and the Internet of Things. In this paper, the usability and fundamental limits of joint RF and solar cell or photovoltaic harvesting based M2M communication systems are studied and presented. The derived theoretical bounds are in essence based on the Shannon capacity theorem, combined with selected propagation loss models, assumed additional link nonidealities, diversity processing, as well as the given energy harvesting and storage capabilities. Fundamental performance limits and available capacity of the communicating link are derived and analyzed, together with extensive numerical results evaluated in different practical scenarios, including realistic implementation losses and state-of-the-art printed supercapacitor performance figures with voltage doubler-based voltage regulator. In particular, low power sensor type communication applications using passive and semi-passive wake-up radio (WuR) are addressed in the study. The presented analysis principles and results establish clear feasibility regions and performance bounds for wireless energy harvesting based low rate M2M communications in the future IoT networks.

Near-UV electroluminescence in unipolar-doped, bipolar-tunneling GaN/AlN heterostructures.

Cross-gap light emission is reported in n-type unipolar GaN/AlN double-barrier heterostructure diodes at room temperature. Three different designs were grown on semi-insulating bulk GaN substrates using molecular beam epitaxy (MBE). All samples displayed a single electroluminescent spectral peak at 360 nm with full-width at half-maximum (FWHM) values no greater than 16 nm and an external quantum efficiency (EQE) of ≈0.0074% at 18.8 mA. In contrast to traditional GaN light emitters, p-type doping and p-contacts are completely avoided, and instead, holes are created in the GaN on the emitter side of the tunneling structure by direct interband (that is, Zener) tunneling from the valence band to the conduction band on the collector side. The Zener tunneling is enhanced by the high electric fields (~5 × 106 V cm-1) created by the notably large polarization-induced sheet charge at the interfaces between the AlN and GaN.

Correlation of end tidal carbon dioxide, amplitude spectrum area, and coronary perfusion pressure in a porcine model of cardiac arrest.

Amplitude Spectrum Area (AMSA) values during ventricular fibrillation (VF) correlate with myocardial energy stores and predict defibrillation success. By contrast, end tidal CO2 (ETCO2) values provide a noninvasive assessment of coronary perfusion pressure and myocardial perfusion during cardiopulmonary resuscitation (CPR). Given the importance of the timing of defibrillation shock delivery on clinical outcome, we tested the hypothesis that AMSA and ETCO2 correlate with each other and can be used interchangably to correlate with myocardial perfusion in an animal laboratory preclinical, randomized, prospective investigation. After 6 min of untreated VF, 12 female pigs (32 ± 1 Kg), isoflurane anesthetized pigs received sequentially 3 min periods of standard (S) CPR, S-CPR+ an impedance threshold device (ITD), and then active compression decompression (ACD) + ITD CPR Hemodynamic, AMSA, and ETCO2 measurements were made with each method of CPR The Spearman correlation and Friedman tests were used to compare hemodynamic parameters. ETCO2, AMSA, coronary perfusion pressure, cerebral perfusion pressure were lowest with STD CPR, increased with STD CPR + ITD and highest with ACD CPR + ITD Further analysis demonstrated a positive correlation between AMSA and ETCO2 (r = 0.37, P = 0.025) and between AMSA and key hemodynamic parameters (P < 0.05). This study established a moderate positive correlation between ETCO2 and AMSA These findings provide the physiological basis for developing and testing a novel noninvasive method that utilizes either ETCO2 alone or the combination of ETCO2 and AMSA to predict when defibrillation might be successful.

Chest compliance is altered by static compression and decompression as revealed by changes in anteroposterior chest height during CPR using the ResQPUMP in a human cadaver model.

INTRODUCTION: Chest compliance plays a fundamental role in the generation of circulation during cardiopulmonary resuscitation (CPR). To study potential changes in chest compliance over time, anterior posterior (AP) chest height measurements were performed on newly deceased (never frozen) human cadavers during CPR before and after 5min of automated CPR. We tested the hypothesis that after 5min of CPR chest compliance would be significantly increased. METHODS: Static compression (30, 40, and 50kg) and decompression forces (-10, -15kg) were applied with a manual ACD-CPR device (ResQPUMP, ZOLL) before and after 5min of automated CPR. Lateral chest x-rays were obtained with multiple reference markers to assess changes in AP distance. RESULTS: In 9 cadavers, changes (mean±SD) in the AP distance (cm) during the applied forces were 2.1±1.2 for a compression force of 30kg, 2.9±1.3 for 40kg, 4.3±1.0 for 50kg, 1.0±0.8 for a decompression force of -10kg and 1.8±0.6 for -15kg. After 5min of automated CPR, AP excursion distances were significantly greater (p<0.05). AP distance increased to 3.7±1.4 for a compression force of 30kg, 4.9±1.6 for 40kg, 6.3±1.9 for 50kg, 2.3±0.9 for -10kg of lift and 2.7±1.1 for -15kg of lift. CONCLUSIONS: These data demonstrate chest compliance increases significantly over time as demonstrated by the significant increase in the measured AP distance after 5min of CPR. These findings suggest that adjustments in compression and decompression forces may be needed to optimize CPR over time.

Modest utility of quantitative measures in (18)F-fluorodeoxyglucose positron emission tomography scanning for the diagnosis of aortic prosthetic graft infection.

BACKGROUND: The clinical dilemma in suspected aortic graft infection (AGI) is how to noninvasively obtain a reliable proof of infection. In addition to confirming the presence of infection, obtaining information regarding the extent of infection to select a proper strategy for reoperation is also necessary. Therefore, developing a more reliable noninvasive physiologic approach to detect infected prostheses is required. (18)F-fluorodeoxyglucose positron emission tomography scanning ((18)F-FDG PET) has been suggested to have a pivotal role in the detection of AGI. In this study, we assessed the contribution of two (semi) quantitative parameters-maximal standardized uptake value (SUVmax) and tissue-to-background ratio (TBR)-and of two visual parameters-fluorodeoxyglucose (FDG) distribution patterns and visual grading scale-in the final confirmation of the diagnosis of AGI. METHODS: Patients with a central aortic prosthetic graft and symptoms clinically suggestive of AGI were gathered from a prospectively maintained database. Included were those who underwent (18)F-FDG PET scanning combined with computed tomography angiography and in whom periprosthetic samples were taken at some stage in the diagnostic process. AGI was considered proven in case of a positive culture and compared with a group with negative cultures. Positive predictive values (PPVs) and negative predictive values (NPVs) were calculated. Receiver operating characteristics curves were used to assess the ability of SUVmax and TBR to identify the presence and absence of AGI (ie, accuracy). RESULTS: In 37 of 77 patients with suspected AGI, (18)FDG-PET and perigraft material for culturing was obtained. The tissue culture was positive in 21 of these 37 patients (56.7%). Mean ± standard deviation SUVmax for proven infection was 8.1 ± 3.7 (range, 3.6-18.5) and TBR was 5.9 ± 2.7 (range, 1.7-13.0). The area under the curve for SUVmax was 0.78 (95% confidence interval, 0.63-0.93). A cutoff value of 8 yielded a PPV of 80% and a NPV of 54%. The area under the curve for TBR was 0.70 (95% confidence interval, 0.52-0.87). A cutoff value of 6 yielded a PPV of 73% and NPV of 52%. The PPVs for the visual grading scale and (18)F-FDG distribution patterns were 75% and 61%, respectively; the NPVs were 77% and 67%, respectively. CONCLUSIONS: Our study, performed in a small sample of patients suspected of AGI, showed that the diagnostic abilities of quantitative and visual (18)F-FDG PET parameters are modest.

Endovascular treatment of mycotic aortic aneurysms: a European multicenter study.

BACKGROUND: Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection-related complications and long-term survival. METHODS AND RESULTS: All EVAR treated MAAs, between 1999 and 2013 at 16 European centers, were retrospectively reviewed. One hundred twenty-three patients with 130 MAAs were identified. Mean age was 69 years (range 39-86), 87 (71%) were men, 58 (47%) had immunodeficiency, and 47 (38%) presented with rupture. Anatomic locations were ascending/arch (n=4), descending (n=34), paravisceral (n=15), infrarenal aorta (n=63), and multiple (n=7). Treatments were thoracic EVAR (n=43), fenestrated/branched EVAR (n=9), and infrarenal EVAR (n=71). Antibiotic was administered for mean 30 weeks. Mean follow-up was 35 months (range 1 week to 149 months). Six patients (5%) were converted to open repair during follow-up. Survival was 91% (95% confidence interval, 86% to 96%), 75% (67% to 83%), 55% (44% to 66%), and 41% (28% to 54%) after 1, 12, 60, and 120 months, respectively. Infection-related death occurred in 23 patients (19%), 9 after discontinuation of antibiotic treatment. A Cox regression analysis demonstrated non-Salmonella-positive culture as predictors for late infection-related death. CONCLUSIONS: Endovascular treatment of MAA is feasible and for most patients a durable treatment option. Late infections do occur, are often lethal, and warrant long-term antibiotic treatment and follow-up. Patients with non-Salmonella-positive blood cultures were more likely to die from late infection.

Nephrectomy in autosomal dominant polycystic kidney disease: a patient with exceptionally large, still functioning kidneys.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It is characterized by progressive cyst formation in both kidneys, often leading to end-stage kidney disease. Indications for surgical removal of an ADPKD kidney include intractable pain, hematuria, infection, or exceptional enlargement and small abdominal cavity hampering implantation of a donor kidney. We report the case of an extraordinarily large ADPKD kidney weighing 8.7 kg (19.3 lb) with a maximal length of 48 cm (19 inch), and with cysts filled with both clear and bloody fluid.

Graft-appendiceal fistula treated with a rifampicin-silver in-situ graft.

BACKGROUND: We report a 52-year-old male presenting with a graft-appendiceal fistula four years after placement of an aorto-bifemoral Dacron prosthesis. CASE REPORT: After appendectomy and total graft removal, the patient was treated with an in-situ repair using a rifampicin-silver graft. This kind of repair has only been reported in an animal study. RESULTS: This infected aortic graft was treated successfully with a rifampicin-silver graft with a follow-up of 15 months without complications. CONCLUSION: In-situ repair of a graft-appendiceal fistula with a rifampicin-silver graft seems a promising strategy. The long-term outcome needs to be studied.

Outcome of endovascular reintervention for significant stenosis at infrainguinal bypass anastomoses.

OBJECTIVE: The durability of an infrainguinal bypass may be hampered by development of stenosis at the anastomoses. We describe the patency of percutaneous transluminal angioplasty (PTA) of these anastomotic stenoses. METHODS: Any venous or prosthetic infrainguinal bypass with a hemodynamically significant anastomotic stenosis, symptomatic or asymptomatic, was considered a bypass at risk (BAR) for occlusion. All BARs undergoing PTA in two large vascular referral centers between January 2005 and December 2010 were retrospectively reviewed. Procedural success was defined as <30% residual stenosis. Primary end points were primary, assisted primary, and secondary patency rates. RESULTS: Included were 43 patients with 43 BARs (31 venous, 11 prosthetic, and 1 unknown conduit; 19 supragenicular and 24 infragenicular). Mean follow-up was 17 months (range, 0-57 months). Procedures constituted 48 interventions for proximal (n = 13), distal (n = 25), or combined (n = 5) anastomotic stenoses. Procedural success was 96%. The primary, assisted primary, and secondary patency rates were 58%, 85%, and 88%, respectively, at 2 years. CONCLUSIONS: PTA for infrainguinal BAR due to anastomotic stenosis is technically feasible with acceptable durability. PTA for these anastomotic stenoses may be considered a safe option as the first-line treatment.

Accountable care organizations and radiology: threat or opportunity?

Although the anticipated rise of accountable care organizations brings certain potential threats to radiologists, including direct threats to revenue and indirect systemic changes jeopardizing the bargaining leverage of radiology groups, accountable care organizations, and other integrated health care delivery models may provide radiology with an important opportunity to reassert its leadership and assume a more central role within health care systems. Capitalizing on this potential opportunity, however, will require radiology groups to abandon the traditional "film reader" mentality and engage actively in the design and implementation of nontraditional systems service lines aimed at adding differentiated value to larger health care organizations. Important interlinked and mutually reinforcing components of systems service lines, derived from radiology's core competencies, may include utilization management and decision support, IT leadership, quality and safety assurance, and operational enhancements to meet organizational goals. Such systems-oriented service products, tailored to the needs of individual integrated care entities and supported by objective performance metrics, may provide market differentiation to shield radiology from commoditization and could become an important source of new nonclinical revenue.

[Vacuum-assisted closure therapy for exposed vascular prosthesis in the groin]. / Vacuümtherapie bij blootliggende vaatprothese in lies.

Groin infections are a severe complication in vascular surgery. The treatment of a groin infection with exposed vascular prosthetic material is challenging. Vacuum-assisted closure (VAC) is a therapy frequently used to close wounds. In groin wounds with exposed vascular prosthetic material, however, VAC has been contraindicated because of the risk of bleeding. We successfully treated 17 groin infections with exposed vascular prosthetic material from 2009 to 2011 by using a double-sponge technique (a combination of polyvinyl alcohol and polyurethane sponges and a continuous negative pressure of 50 mmHg); there were no complications involving haemorrhaging, amputations or re-infection. At a median follow-up duration of 380 days, no further complications occurred and all prostheses could be retained. The double-sponge technique appears to be an effective and simple method for closing an infected groin with preservation of the underlying prosthetic material.

Negative pressure wound therapy on exposed prosthetic vascular grafts in the groin.

OBJECTIVE: This study assessed the outcome of vacuum-assisted closure (VAC) as primary therapy for exposed prosthetic vascular grafts in the groin (Szilagyi III). METHODS: The study included all consecutive patients with Szilagyi III groin infections and exposed prosthetic graft material from 2009 to 2011. After initial wound debridement, VAC was applied using a two-layer combination, consisting of polyvinyl alcohol and polyurethane sponges. Continuous negative pressure was set on a maximum of 50 mm Hg. All patients received complementary antibiotic therapy. The primary end point was defined as complete wound closure. Secondary end points comprised bleeding complications, amputation, and death. RESULTS: The study evaluated 15 patients with 17 Szilagyi III groin infections. Mean total length of VAC therapy was 43 days (range, 14-76 days). Mean time until complete healing was 51 days (range, 24-82 days). Mean length of VAC therapy in the hospital was 21 days (range, 5-61 days). Eleven patients received continued VAC treatment at home for a mean length of 22 days (range, 5-69 days). Complete healing was achieved in 14 groins (82%). Three failures due to persisting infection, persisting necrosis, and a pseudomonas infection were noted. No bleeding complications, amputations, or late reinfections occurred. Median follow-up was 380 days (range, 56-939 days). Despite therapy failure, all 17 grafts were preserved. CONCLUSIONS: VAC therapy on an exposed prosthetic vascular graft in the groin is safe and feasible when applying a combination of polyvinyl alcohol and polyurethane foam dressing and 50 mm Hg of continuous negative pressure, resulting in midterm graft preservation.