A COVID-19 monitoring process for healthcare workers utilizing occupational health.

BACKGROUND: Hospital-based occupational health (HBOH) is uniquely positioned to not only prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, but to care for healthcare workers (HCWs) sick with coronavirus disease 2019 (COVID-19). AIMS: The primary objective of this study is to describe a system where HBOH services were adapted to provide a monitoring programme whereby HCWs with SARS-CoV-2 received daily evaluations and treatment options in order to improve access to care, and to report the clinical outcomes and predictors of hospitalization in HCWs enrolled in the programme. A secondary objective is to compare clinical outcomes to data on national HCWs with COVID-19. METHODS: This retrospective cohort study used survey data collected on HCWs at a university health system with COVID-19 from 1 March 2020 through 1 December 2021. A firth regression model was used to examine the unadjusted and adjusted association between clinical factors and hospitalization. RESULTS: The study cohort included 4814 HCWs with COVID-19. Overall hospitalizations were 119 (2%), and there were six deaths (0.12%). Predictors of hospitalization include several co-morbidities and symptoms. A total of 1835 HCWs monitored before vaccine or monoclonal antibody availability were compared with data on U.S. HCWs in a similar time period. The monitored HCWs had a lower rate of co-morbidities (19% versus 44%, P < 0.001), a lower hospitalization rate (3% versus 8% P < 0.001) and case-fatality rate (0.11% versus 0.95% P < 0.001). CONCLUSIONS: This monitoring strategy for COVID-19 may be feasible for HBOH systems to implement and improve access to care, but more data are needed to determine if it improves outcomes.

Anatomy of a Transcatheter Mitral Valve Service.

Transcatheter mitral therapies offer treatment options to selected patients who are unable to undergo open procedures due to prohibitive surgical risk. Data detailing the design and structure of transcatheter mitral services to ensure appropriate patient selection and tailored management strategies is lacking. We report our initial experience of developing and running a purpose-built transcatheter mitral service. The nature and number of referral sources, the multi-disciplinary make-up of the dedicated Mitral Heart Team and the use of integrative imaging assessment with incorporation of computational solutions are discussed. In addition, a summary of the clinical decision-making process is presented. This report sets out a framework from which future clinics can evolve to improve and streamline the delivery of transcatheter mitral therapies.

"Between a rock and the mitral valve space": Transcatheter mitral valve-in-valve implantation for paravalvular leak and refractory hemolysis complicated by circumflex coronary occlusion.

Transcatheter mitral valve implantation (TMVI) is an emerging field in structural cardiology. A particularly difficult group to treat is high-risk patients requiring valve in mitral annular calcification (ViMAC) intervention, with overall poor procedural success and outcomes in recent registries. This case highlights an unusual complication of paravalvular regurgitation (PVL) through the uncovered stent frame of a balloon expandable transcatheter heart valve (THV) on the left ventricular side of the prosthesis, leading to mechanical hemolysis and subsequent anuric renal failure post a ViMAC procedure. Attempts to treat the PVL with an occlusion plug device were unsuccessful and led to left circumflex coronary occlusion secondary to mechanical compression of the vessel in the posterior mitral valve annulus, a previously unreported phenomenon. A repeat valve-in-valve procedure was performed to treat the PVL, and immediate angioplasty resolved the left circumflex occlusion. High-risk patients requiring TMVI pose multiple challenges to Heart Teams in the treatment of valve pathology. Optimal procedural planning, multimodality imaging, improved THVs, and the awareness of potential complications are fundamental in overcoming the learning curve of TMVI and improved outcome for patients requiring ViMAC.

Plasma levels of soluble membrane attack complex are elevated despite viral suppression in HIV patients with poor immune reconstitution.

The complement system is now a therapeutic target for the management of serious and life-threatening conditions such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, glomerulonephritis and other diseases caused by complement deficiencies or genetic variants. As complement therapeutics expand into more clinical conditions, monitoring complement activation is increasingly important, as is the baseline levels of complement activation fragments in blood or other body fluid levels. Although baseline complement levels have been reported in the literature, the majority of these data were generated using non-standard assays and with variable sample handling, potentially skewing results. In this study, we examined the plasma and serum levels of the soluble membrane attack complex of complement (sMAC). sMAC is formed in the fluid phase when complement is activated through the terminal pathway. It binds the regulatory proteins vitronectin and/or clusterin and cannot insert into cell membranes, and can serve as a soluble diagnostic marker in infectious disease settings, as previously shown for intraventricular shunt infections. Here we show that in healthy adults, serum sMAC levels were significantly higher than those in plasma, that plasma sMAC levels were similar between in African Americans and Caucasians and that plasma sMAC levels increase with age. Plasma sMAC levels were significantly higher in virally suppressed people living with HIV (PLWH) compared to non-HIV infected healthy donors. More specifically, PLWH with CD4+ T cell counts below 200 had even greater sMAC levels, suggesting diagnostic value in monitoring sMAC levels in this group.

Transcatheter aortic valve implantation for severe aortic stenosis in the Australian regional population.

OBJECTIVE: To compare clinical and functional outcomes of regional and urban patients after transcatheter aortic valve implantation for severe aortic stenosis. METHODS: Data were collected at patient follow-up post-transcatheter aortic valve implantation at 30 days and 12 months. Patients were stratified by residential postcodes into remoteness areas using the Australian Statistical Geography Standard. DESIGN: Retrospective cohort study. SETTING: Single-centre tertiary referral hospital. PARTICIPANTS: Patients undergoing transcatheter aortic valve implantation (n = 142) from 2009 to 2018 were analysed, with 77 patients (54.2%) residing in regional Victoria and New South Wales. MAIN OUTCOME MEASURES: Procedural success, adverse event rates, readmission rates, mortality rates, loss to follow-up and functional improvement. RESULTS: Patients residing in regional areas had a lower mean age (81.8 vs 83.7 years) and proportion of Stage 4 or 5 chronic kidney disease (1.3% vs 9.2%), compared with urban patients. Procedural characteristics and immediate post-procedural outcomes were similar between both groups. There was no statistically significant difference in mortality, readmission rates or loss to follow-up between the two cohorts. Regional patients demonstrated poorer rates of functional improvement at 30 days (50.7% vs 67.7%); however, this difference was not sustained at 12 months (79.2% vs 71.0%). Frailty was demonstrated to be an independent predictor of poor 30-day functional improvement. CONCLUSION: Regional patients treated with transcatheter aortic valve implantation for severe aortic stenosis have non-inferior 30-day and 12-month outcomes, when compared with urban patients. Frailty is a predictor of poor functional improvement post-transcatheter aortic valve implantation.

Contemporary review of severe aortic stenosis.

Severe aortic stenosis (AS) is the most common form of valvular heart disease in the developed world, with a rising prevalence due to an ageing Australian population. Transcatheter aortic valve implantation (TAVI) offers a less invasive option for the treatment of severe AS, with evidence supporting TAVI compared with medical therapy in inoperable patients and superior with surgical aortic valve replacement (SAVR) in high-risk patients. Equal outcomes have been observed in all-comer intermediate-risk populations. The Heart Team utilises a shared decision-making approach between physicians and surgeons in risk-stratifying patients and reduces the intrinsic bias that may occur if decisions are made in isolation. Geriatric assessment is useful for identifying preoperative frailty, a major risk factor for death post-aortic valve intervention. In severe AS, a decision can be made collaboratively to pursue TAVI, SAVR, a Ross Procedure or conservative management. The learning curve associated with TAVI has improved markedly, with overall complication rates decreasing around the world. Contemporary changes in practice, such as conscious sedation without general anaesthesia, expedited recovery and early discharge, will likely improve cost-effectiveness. In 2018, TAVI is a well-established procedure in Australia that has revolutionised the management of severe AS. In the future, with an expanding elderly population, the number of patients to benefit from transcatheter therapies for severe AS is hypothesised to increase 4-10-fold. Heart Team assessment is crucial in patients with severe AS to direct appropriate management.

Subthalamic nucleus deep brain stimulation in primary cervical dystonia.

OBJECTIVES: The globus pallidus internus (GPi) has been the primary target for deep brain stimulation (DBS) to treat severe medication-refractory dystonia. Some patients with primary cervical or segmental dystonia develop subtle bradykinesia occurring in previously nondystonic body regions during GPi DBS. Subthalamic nucleus (STN) DBS may provide an alternative target choice for treating dystonia, but has only been described in a few short reports, without blinded rating scales, statistical analysis, or detailed neuropsychological studies. METHODS: In this prospective pilot study, we analyzed the effect of bilateral STN DBS on safety, efficacy, quality of life, and neuropsychological functioning in 9 patients with medically refractory primary cervical dystonia. Severity of dystonia was scored by a blinded rater (unaware of the patient's preoperative or postoperative status) using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) preoperatively and 3, 6, and 12 months postsurgery. Lead location, medications, and adverse events were also measured. RESULTS: STN DBS was well-tolerated with no serious adverse effects. The TWSTRS total score improved (p < 0.001) from a mean (±SEM) of 53.1 (±2.57), to 19.6 (±5.48) at 12 months. Quality of life measures were also improved. STN DBS induced no consistent neuropsychological deficits. Several patients reported depression in the study and 3 had marked weight gain. No patients developed bradykinetic side effects from stimulation, but all patients developed transient dyskinetic movements during stimulation. CONCLUSIONS: This prospective study showed that bilateral STN DBS resulted in improvement in dystonia and suggests that STN DBS may be an alternative to GPi DBS for treating primary cervical dystonia. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that bilateral subthalamic nucleus deep brain stimulation results in significant improvement in cervical dystonia without bradykinetic side effects.

Tunable dipolar magnetism in high-spin molecular clusters.

We report on the Fe17 high-spin molecular cluster and show that this system is an exemplification of nanostructured dipolar magnetism. Each Fe17 molecule, with spin S=35/2 and axial anisotropy as small as D approximately -0.02 K, is the magnetic unit that can be chemically arranged in different packing crystals while preserving both the spin ground state and anisotropy. For every configuration, molecular spins are correlated only by dipolar interactions. The ensuing interplay between dipolar energy and anisotropy gives rise to macroscopic behaviors ranging from superparamagnetism to long-range magnetic order at temperatures below 1 K.

Pentanuclear homoleptic M(5)L(6) (M = Mn(II), Co(II), Zn(II)) complexes formed by strict self-assembly.

A series of trigonal bipyramidal pentanuclear complexes involving the alkoxo-diazine ligands poap and p3oap, containing the M(5)[mu-O](6) core is described, which form by a strict self-assembly process. [Co(5)(poap-H)(6)](ClO(4))(4).3H(2)O (1), [Mn(5)(poap-H)(6)](ClO(4))(4).3.5CH(3)OH.H(2)O (2), [Mn(5)(p3oap-H)(6)](ClO(4))(4).CH(3)CH(2)OH.3H(2)O (3), and [Zn(5)(poap-H)(6)](ClO(4))(4).2.5H(2)O (4) are homoleptic pentanuclear complexes, where there is an exact match between the coordination requirements of the five metal ions in the cluster, and the available coordination pockets in the polytopic ligand. [Zn(4)(poap)(poap-H)(3)(H(2)O)(4)] (NO(3))(5).1.5H(2)O (5) is a square [2 x 2] grid with a Zn(4)[mu-O](4) core, and appears to result from the presence of NO(3), which is thought to be a competing ligand in the self-assembly. X-ray structures are reported for 1, 4, and 5. 1 crystallized in the monoclinic system, space group P2(1)/n with a = 13.385(1) A, b = 25.797(2) A, c = 28.513(3) A, beta = 98.704(2) degrees, and Z = 4. 4 crystallized in the triclinic system, space group P1 with a = 13.0897(9) A, b = 18.889(1) A, c = 20.506(2) A, alpha = 87.116(1) degrees, beta = 74.280(2) degrees, gamma = 75.809(2) degrees, and Z = 2. 5 crystallized in the monoclinic system, space group P2(1)/n with a = 14.8222(7) A, b = 21.408(1) A, c = 21.6197(9) A, beta = 90.698(1) degrees, and Z = 4. Compounds 1-3 exhibit intramolecular antiferromagnetic coupling.

Follicular dendritic cells (FDC) in retroviral infection: host/pathogen perspectives.

Follicular dendritic cells (FDC) are found in the follicles of virtually all secondary lymphoid tissues. In health, these cells trap and retain antigens (Ag) in the form of immune complexes and preserve them for months in their native conformation. FDC thus serve as a long-term repository of extracellular Ag important for induction and maintenance of memory responses. In retroviral infection, FDC trap and retain large numbers of retroviral particles with profound effects on FDC. FDC-trapped retrovirus induces follicular hyperplasia, and conventional Ag trapped prior to infection are lost and new Ag cannot be trapped. Concomitantly, antibody-forming cells (AFC) specific for Ag lost from FDC decrease followed by loss of specific serum antibody (Ab). Eventually, FDC die and follicular lysis occurs. From the pathogen perspective, binding to FDC is remarkably beneficial, bringing together virus and activated target cells that are highly susceptible to infection. Furthermore, FDC permit HIV to infect surrounding cells even in the presence of a vast excess of neutralizing Ab. Preliminary data suggest that FDC maintain virus infectivity-even when the virus cannot replicate. Thus retrovirus infection monopolizes FDC networks, thereby transforming the FDC Ag repository into a highly infectious retroviral reservoir.

Follicular dendritic cells and human immunodeficiency virus infectivity.

Large amounts of human immunodeficiency virus (HIV) localize on follicular dendritic cells (FDC) in the follicles of secondary lymphoid tissues following viral infection. During clinical latency, active viral infection occurs primarily at these sites. As HIV on FDC is in the form of immune complexes, some of which may be formed with neutralizing antibody, we investigated whether HIV on FDC is infectious. We report here that HIV on FDC is highly infectious. Furthermore, FDC can convert neutralized HIV into an infectious form even in the presence of a vast excess of neutralizing antibody. Thus FDC may provide a mechanism whereby HIV infection can continue in the presence of neutralizing antibody.