The mechanics of setting up a COVID-19 response: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa.

The SARS-CoV-2 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID-19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town's tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves.

Clinical management of COVID-19: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa.

The SARS-CoV-2 pandemic has presented clinicians with an enormous challenge in managing a respiratory virus that is not only capable of causing severe pneumonia and acute respiratory distress syndrome, but also multisystem disease. The extraordinary pace of clinical research, and particularly the surge in adaptive trials of new and repurposed treatments, have provided rapid answers to questions of whether such treatments work, and has resulted in corticosteroids taking centre stage in the management of hospitalised patients requiring oxygen support. Some treatment modalities, such as the role of anticoagulation to prevent and treat potential thromboembolic complications, remain controversial, as does the use of high-level oxygen support, outside of an intensive care unit setting. In this paper, we describe the clinical management of COVID-19 patients admitted to Groote Schuur Hospital, a major tertiary level hospital at the epicentre of South Africa's SARS-CoV-2 epidemic during its first 4 months.

The mechanics of setting up a COVID-19 response: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa

The COVID-19 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID-19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town's tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves

Stability of fungal biomass continuously fed with tannic acid in a non-sterile moving-packed bed reactor.

A number of bacteria and fungi are known to degrade tannins. In this study, the efficiency of the white-rot fungus, Bjerkandera adusta MUT 2295, was evaluated for the treatment of a synthetic solution prepared with tannic acid. Tests were performed in continuously fed, bench-scale, packed-bed reactors, operated under non-sterile conditions with biomass immobilized within PolyUrethane Foam cubes (PUFs). The main parameters monitored to evaluate the process efficiency were: soluble Chemical Oxygen Demand (sCOD), Total Organic Carbon (TOC) removal, and activities. of Tannase and Lignin Peroxidase. At the end of the process, additional parameters were evaluated, including the increase of fungal dry weight and the presence of ergosterol. The reactor was operative for 210 days, with maximum sCOD and TOC removal of 81% and 73%, respectively. The reduction of sCOD and TOC were positively correlated with the detection of Tannase and Lignin Peroxidase (LiP) activities. Increases in biomass within the PUF cubes was associated with increases in ergosterol concentrations. This study proved that the fungal-based system tested was efficient for the degradation of tannic acid over a period of time, and under non-sterile conditions.

Correction to: Reducing surgical site infections following total hip and knee arthroplasty: an Israeli experience.

In the original article, one of the co-author's family name has been published incorrectly.

Effect of cellulose as co-substrate on old landfill leachate treatment using white-rot fungi.

Conventional wastewater treatment technologies are ineffective for remediation of old LandFill Leachate (LFL), and innovative approaches to achieve satisfactory removal of this recalcitrant fraction are needed. This study focused on old LFL treatment with a selected fungal strain, Bjerkandera adusta MUT 2295, through batch and continuous tests, using packed-bed bioreactors under non-sterile conditions. To optimize the process performance, diverse types of co-substrates were used, including milled cellulose from beverage cups waste material. Extracellular enzyme production was assayed, in batch tests, as a function of a) cellulose concentration, b) leachate initial Chemical Oxygen Demand (COD) and Soluble COD (sCOD), and c) co-substrate type. Bioreactors were dosed with an initial start-up of glucose (Rg) or cellulose (Rc). An additional glucose dosage was provided in both reactors, leading to significant performance increases. The highest COD and sCOD removals were i) 63% and 53% in Rg and ii) 54% and 51% in Rc.

Reducing surgical site infections following total hip and knee arthroplasty: an Israeli experience.

PURPOSE: To assess the changes observed in surgical site infection (SSI) rates following total joint arthroplasty (TJA) after the introduction of an infection control programme and evaluate the risk factors for the development of these infections. DESIGN: Prospective cohort study. SETTING: Large tertiary medical centre in Israel. METHODS: Data about SSIs and potential prophylaxis-, patient-, and procedure-related risk factors were collected for all patients who underwent elective total hip and total knee arthroplasty during the study period. Multivariant analyses were conducted to determine which significant covariates affected the outcome. RESULTS: During the 76-month study period, SSIs (superficial and deep) occurred in 64 (4.4%) of 1554 patients. As compared with the 34 (7.7%) SSIs that occurred in the first 25 months, there were 23 (4.7%) SSIs in the following 25 months, and only 7 (1.3%) SSIs in the last third of the study (p = 0.058 and <0.001, respectively). A multiple logistic regression model indicated that risk factors for prosthetic joint infection were a National Nosocomial Infections Surveillance (NNIS) System surgical patient risk index score of 1 (OR 1.8; 95% CI 1.1-3.1) or 2 (OR 2.8; 95% CI 1.2-11.8). The incidence of SSI was not correlated with the timing, nor the duration of antibiotic prophylaxis. CONCLUSIONS: The introduction of preventive measures and surveillance coincided with a significant reduction in SSIs following TJA in our institution. The risk of infection correlated with higher scores in the NNIS System surgical patient risk.

Modulating immunogenicity of factor IX by fusion to an immunoglobulin Fc domain: a study using a hemophilia B mouse model.

Essentials Fc-fusion increases a therapeutic's half-life, but FcγR interactions may impact immunogenicity. Species-specific Fc-FcγR interactions allow for mechanistic in vivo studies using mouse models. Fc fusion modulates the immune response to factor IX in hemophilia B mice by eliciting Th1 bias. This model could inform future studies of IgE-associated anaphylaxis in hemophilia B patients. SUMMARY: Background Fc fusion is a platform technology used to increase the circulating half-life of protein and peptide therapeutics. However, there are potential immunological consequences with this approach, such as changes in the molecule's immunogenicity as well as possible interactions with a repertoire of Fc receptors (FcR) that can modulate immune responses. Objectives/Methods Using a mouse hemophilia B (HB) model, we compared the immune responses to infusions of recombinant human factor IX (hFIX) and hFIX fused to mouse IgG2a-Fc (hFIX-mFc). The mFc was employed to allow species-specific Fc-FcγR interactions. Results Although treatment with hFIX-mFc altered the early development of anti-FIX IgG, no significant differences in anti-FIX antibody titers were observed at the end of the treatment regimen (5 weeks) or upon anamnestic response (5 months). However, treatment with hFIX-mFc elicited higher FIX-neutralizing antibody levels and resulted in reduced IgE titers compared with the hFIX-treated group. Additionally, differences in plasma cytokine levels and in vitro CD4+ T-cell responses suggest that whereas hFIX treatment triggered a Th2-biased immune response, hFIX-mFc treatment induced Th1-biased CD4+ T cells. We also show that hFIX-mFc bound to soluble FcγRs and engaged with FcγRs on different cell types, which may impact antigen presentation. Conclusions These studies provide a model system to study how Fc-fusion proteins may affect immune mechanisms. We used this model to demonstrate a plausible mechanism by which Fc fusion may modulate the IgE response to hFIX. This model may be appropriate for investigating the rare but severe IgE-mediated anaphylaxis reaction to hFIX infusions in HB patients.

A High-Resolution Imaging Technique using a Whole-body, Research Photon Counting Detector CT System.

A high-resolution (HR) data collection mode has been introduced to the whole-body, research photon-counting-detector CT system installed in our laboratory. In this mode, 64 rows of 0.45 mm × 0.45 mm detectors pixels were used, which corresponded to a pixel size of 0.225 mm × 0.225 mm at the iso-center. Spatial resolution of this HR mode was quantified by measuring the MTF from a scan of a 50 micron wire phantom. An anthropomorphic lung phantom, cadaveric swine lung, temporal bone and heart specimens were scanned using the HR mode, and image quality was subjectively assessed by two experienced radiologists. Comparison of the HR mode images against their energy integrating system (EID) equivalents using comb filters was also performed. High spatial resolution of the HR mode was evidenced by the MTF measurement, with 15 lp/cm and 20 lp/cm at 10% and 2% MTF. Images from anthropomorphic phantom and cadaveric specimens showed clear delineation of small structures, such as lung vessels, lung nodules, temporal bone structures, and coronary arteries. Temporal bone images showed critical anatomy (i.e. stapes superstructure) that was clearly visible in the PCD system but hardly visible with the EID system. These results demonstrated the potential application of this imaging mode in lung, temporal bone, and vascular imaging. Other clinical applications that require high spatial resolution, such as musculoskeletal imaging, may also benefit from this high resolution mode.

Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration.

Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After 2 wk, S1 was dilated compared with controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish increased and contained a higher number of bromodeoxyuridine (BrdU)-labeled cells after 2 wk of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish, a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation.

Reassessment of the transhydrogenase/malate shunt pathway in Clostridium thermocellum ATCC 27405 through kinetic characterization of malic enzyme and malate dehydrogenase.

Clostridium thermocellum produces ethanol as one of its major end products from direct fermentation of cellulosic biomass. Therefore, it is viewed as an attractive model for the production of biofuels via consolidated bioprocessing. However, a better understanding of the metabolic pathways, along with their putative regulation, could lead to improved strategies for increasing the production of ethanol. In the absence of an annotated pyruvate kinase in the genome, alternate means of generating pyruvate have been sought. Previous proteomic and transcriptomic work detected high levels of a malate dehydrogenase and malic enzyme, which may be used as part of a malate shunt for the generation of pyruvate from phosphoenolpyruvate. The purification and characterization of the malate dehydrogenase and malic enzyme are described in order to elucidate their putative roles in malate shunt and their potential role in C. thermocellum metabolism. The malate dehydrogenase catalyzed the reduction of oxaloacetate to malate utilizing NADH or NADPH with a kcat of 45.8 s(-1) or 14.9 s(-1), respectively, resulting in a 12-fold increase in catalytic efficiency when using NADH over NADPH. The malic enzyme displayed reversible malate decarboxylation activity with a kcat of 520.8 s(-1). The malic enzyme used NADP(+) as a cofactor along with NH4 (+) and Mn(2+) as activators. Pyrophosphate was found to be a potent inhibitor of malic enzyme activity, with a Ki of 0.036 mM. We propose a putative regulatory mechanism of the malate shunt by pyrophosphate and NH4 (+) based on the characterization of the malate dehydrogenase and malic enzyme.

End-stage renal disease and survival in people with diabetes: a national database linkage study.

BACKGROUND: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). AIM: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival. METHODS: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration and National Records of Scotland death data. Survival analyses were modelled with Cox regression. RESULTS: Point prevalence of chronic kidney disease (CKD)5 in 2008 was 1.63% of 19 414 people with type 1 diabetes (T1DM) compared with 0.58% of 167 871 people with type 2 diabetes (T2DM) (odds ratio for DM type 0.97, P = 0.77, on adjustment for duration. Although 83% of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving RRT, there was no difference when adjusted for age, sex and DM duration (odds ratio for DM type 0.83, P = 0.432). Diabetic nephropathy was the primary renal diagnosis in 91% of people with T1DM and 58% of people with T2DM on RRT. Median survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM and 2.16 years (95% CI: 1.92, 2.38) in T2DM. CONCLUSION: Considerable numbers of patients with diabetes continue to progress to CKD5 and RRT. Almost half of all RRT cases in T2DM are considered to be due to conditions other than diabetic nephropathy. Median survival time for people with diabetes from initiation of RRT remains poor. These prevalence data are important for future resource planning.

Enhancing the effectiveness of diabetes self-management education: the diabetes literacy project.

Patient empowerment through self-management education is central to improving the quality of diabetes care and preventing Type 2 Diabetes. Although national programs exist, there is no EU-wide strategy for diabetes self-management education, and patients with limited literacy face barriers to effective self-management. The Diabetes Literacy project, initiated with the support of the European Commission, aims to fill this gap. The project investigates the effectiveness of diabetes self-management education, targeting people with or at risk of Type 2 Diabetes in the 28 EU Member States, as part of a comprehensive EU-wide diabetes strategy. National diabetes strategies in the EU, US, Taiwan, and Israel are compared, and diabetes self-management programs inventorized. The costs of the diabetes care pathway are assessed on a per person basis at national level. A comparison is made of the (cost)-effectiveness of different methods for diabetes self-management support, and the moderating role of health literacy, organization of the health services, and implementation fidelity of education programs are considered. Web-based materials are developed and evaluated by randomized trials to evaluate if interactive internet delivery can enhance self-management support for people with lower levels of health literacy. The 3-year project started in December 2012. Several literature reviews have been produced and protocol development and research design are in the final stages. Primary and secondary data collection and analysis take place in 2014. The results will inform policy decisions on improving the prevention, treatment, and care for persons with diabetes across literacy levels.

Utilization rates of neuroradiology across neuroscience specialties in the private office setting: who owns or leases the scanners on which studies are performed?

BACKGROUND AND PURPOSE: Recent literature shows an increasing portion of imaging studies being conducted and interpreted by nonradiologists, especially across the modalities with the highest RVUs. We examined the trends in the Medicare technical charges for private office neuroradiology studies submitted by subspecialists to identify utilization trends among MR and CT scanner owners or lessees over the last decade. MATERIALS AND METHODS: The number of neuroradiology studies performed on MR and CT machines owned or leased in private offices was determined from the CMS PSPSMF for 1998-2008. Studies billed through technical and global charges were aggregated. Utilization rates and utilization rate CAGRs were computed by specialty and by imaging study. RESULTS: Between 1998 and 2008, MR studies grew by a factor of 2.5 and CT studies grew by 2.1. In 2008, radiologists charged the technical/global fee in 1,386,669 (56.6%), neurologists in 82,360 (3.4%), neurosurgeons in 29,218 (1.2%), multi/IDTF in 617,933 (25.2%), and other specialists in 334,843 (13.7%) of neuroradiology cases. Changes from the 1998 base rate to the 2008 rate per 1000 Medicare beneficiaries were 24.1 to 39.7 for radiologists, 1.03 to 2.4 for neurologists, 0.15 to 0.84 for neurosurgeons, 2.2 to 17.7 for multi/IDTF, and 1.3 to 9.6 for other specialists. All specialties, except for multi/IDTF, showed greater MR utilization increases than CT. Neurology (CAGR of 10.6%), neurosurgery (22.1%), multi/IDTF (23.2%), and other specialists' (24.6%) MR growth outpaced that of radiology's (5.3%). CONCLUSIONS: All nonradiologists showed greater overall utilization growth in private office neuroradiology than did radiology. Also, nonradiologists generally showed greater utilization increases in MR than CT. Radiologists' private office neuroradiology technical fee share shrank from 83.6% to 56.6% between 1998 and 2008.

[Efficacy of reamberin in treating heavy acute intestinal infection in children].

The current health conditions dictate the need to reduce the time of patient treatment in hospital and require rational use of drugs. Reduction of the duration of intoxication syndrome in severe forms of intestinal infections in children depends on infusion therapy and choice of solutions for intravenous administration. Reamberin is generation IV infusion preparation for intensive care, representing a balanced isotonic detoxicant infusion solution based on succinic acid. Using reamberin ensures a significant decrease in the time of stay in hospital for children with severe forms of intestinal infections, which is achieved by reducing the duration of endogenous intoxication.

A case of Crohn's disease complicated by adult onset Still's disease.

Arthritis and arthralgia are the most common extra-intestinal manifestations of Inflammatory Bowel Disease (IBD), occurring in up to a third of patients. These may affect the peripheral or axial skeletal system and may or may not reflect disease activity. As a result, it is challenging to identify an alternative diagnosis to account for joint manifestations in the setting of IBD. We describe a case of a 30 year old woman with quiescent Crohn's colitis who presented with 2 weeks of fever, flitting arthralgia, a sore throat and a nocturnal rash on her thighs. She denied any gastrointestinal symptoms to suggest a flare up of IBD. Investigations revealed a neutrophilia and a markedly elevated serum ferritin. The patient met all four major and several minor Yamaguchi criteria for Adult Onset Still's Disease (AOSD). She was treated with corticosteroids and analgesia with resolution of her symptoms and normalisation of her biochemical markers. While joint manifestations are the most common extra-intestinal symptoms of Inflammatory Bowel Disease, atypical presentations should raise the concern of an additional diagnosis. This case represents a rare presentation of Crohn's disease complicated by AOSD.

Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in normoxia in normal supine humans.

We hypothesized that some of the heterogeneity of pulmonary blood flow present in the normal human lung in normoxia is due to hypoxic pulmonary vasoconstriction (HPV). If so, mild hyperoxia would decrease the heterogeneity of pulmonary perfusion, whereas it would be increased by mild hypoxia. To test this, six healthy nonsmoking subjects underwent magnetic resonance imaging (MRI) during 20 min of breathing different oxygen concentrations through a face mask [normoxia, inspired O(2) fraction (Fi(O(2))) = 0.21; hypoxia, Fi(O(2)) = 0.125; hyperoxia, Fi(O(2)) = 0.30] in balanced order. Data were acquired on a 1.5-T MRI scanner during a breath hold at functional residual capacity from both coronal and sagittal slices in the right lung. Arterial spin labeling was used to quantify the spatial distribution of pulmonary blood flow in milliliters per minute per cubic centimeter and fast low-angle shot to quantify the regional proton density, allowing perfusion to be expressed as density-normalized perfusion in milliliters per minute per gram. Neither mean proton density [hypoxia, 0.46(0.18) g water/cm(3); normoxia, 0.47(0.18) g water/cm(3); hyperoxia, 0.48(0.17) g water/cm(3); P = 0.28] nor mean density-normalized perfusion [hypoxia, 4.89(2.13) ml x min(-1) x g(-1); normoxia, 4.94(1.88) ml x min(-1) x g(-1); hyperoxia, 5.32(1.83) ml x min(-1) x g(-1); P = 0.72] were significantly different between conditions in either imaging plane. Similarly, perfusion heterogeneity as measured by relative dispersion [hypoxia, 0.74(0.16); normoxia, 0.74(0.10); hyperoxia, 0.76(0.18); P = 0.97], fractal dimension [hypoxia, 1.21(0.04); normoxia, 1.19(0.03); hyperoxia, 1.20(0.04); P = 0.07], log normal shape parameter [hypoxia, 0.62(0.11); normoxia, 0.72(0.11); hyperoxia, 0.70(0.13); P = 0.07], and geometric standard deviation [hypoxia, 1.88(0.20); normoxia, 2.07(0.24); hyperoxia, 2.02(0.28); P = 0.11] was also not different. We conclude that HPV does not affect pulmonary perfusion heterogeneity in normoxia in the normal supine human lung.

Fertility preservation treatment for young women with autoimmune diseases facing treatment with gonadotoxic agents.

OBJECTIVE: To describe a case series of seven women with SLE and other systemic autoimmune rheumatic diseases (SARDs) who required cyclophosphamide therapy and underwent fertility preservation treatments. METHODS: Of the seven patients reported here, five women had SLE with nephritis, the sixth had immune thrombocytopenia purpura (ITP) and the seventh had microscopic polyangiitis (MPA) with renal involvement. All women were nulliparous and younger than 35 yrs. RESULTS: Patients with SLE underwent in vitro maturation (IVM) of immature oocytes aspirated during a natural menstrual cycle followed by vitrification of the matured oocytes if a male partner was not available, or vitrification of embryos if one was available. The patient with ITP and the patient with MPA underwent gonadotropin ovarian stimulation followed by oocyte or embryo vitrification. All women completed fertility preservation treatment successfully and mature oocytes or embryos (36 and 13, respectively) were vitrified. No complications were associated with this treatment and cytotoxic therapy was initiated as scheduled in all cases. CONCLUSIONS: Oocyte or embryo cryopreservation should be considered for fertility preservation in young women with SARDs who face imminent gonadotoxic treatment. In patients, where gonadotropin ovarian stimulation is deemed unsafe, IVM of immature oocytes, aspirated during a natural menstrual cycle, followed by vitrification or fertilization of the mature oocytes, seems to be safe and feasible. For patients in whom hormonal ovarian stimulation is not contraindicated, this method may be considered depending on the urgency to start cytotoxic therapy.