The impact of non-pharmaceutical interventions on COVID-19 epidemic growth in the 37 OECD member states

We estimated the impact of a comprehensive set of non-pharmeceutical interventions on the COVID-19 epidemic growth rate across the 37 member states of the Organisation for Economic Co-operation and Development during the early phase of the COVID-19 pandemic and between October and December 2020. For this task, we conducted a data-driven, longitudinal analysis using a multilevel modelling approach with both maximum likelihood and Bayesian estimation. We found that during the early phase of the epidemic: implementing restrictions on gatherings of more than 100 people, between 11 and 100 people, and 10 people or less was associated with a respective average reduction of 2.58%, 2.78% and 2.81% in the daily growth rate in weekly confirmed cases; requiring closing for some sectors or for all but essential workplaces with an average reduction of 1.51% and 1.78%; requiring closing of some school levels or all school levels with an average reduction of 1.12% or 1.65%; recommending mask wearing with an average reduction of 0.45%, requiring mask wearing country-wide in specific public spaces or in specific geographical areas within the country with an average reduction of 0.44%, requiring mask-wearing country-wide in all public places or all public places where social distancing is not possible with an average reduction of 0.96%; and number of tests per thousand population with an average reduction of 0.02% per unit increase. Between October and December 2020 work closing requirements and testing policy were significant predictors of the epidemic growth rate. These findings provide evidence to support policy decision-making regarding which NPIs to implement to control the spread of the COVID-19 pandemic.

     

Longitudinal growth on an everolimus‐ versus an MMF‐based steroid‐free immunosuppressive regimen in paediatric renal transplant recipients

Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case‐control study on longitudinal growth over 2 years in steroid‐free pediatric renal transplant recipients. Fourteen patients on a steroid‐free maintenance immunosuppressive regimen consisting of low‐dose everolimus (EVR) in conjunction with low‐dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid‐free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch‐up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid‐free pediatric patients on low‐dose EVR and CsA is not different to that of a matched steroid‐free control group on an immunosuppressive regimen with standard‐dose CNI and MMF. Hence, low‐dose EVR does not appear to negatively impact short‐term growth in pediatric renal transplant recipients.     

Rheopheresis in patients with ischemic diabetic foot syndrome: results of an open label prospective pilot trial

Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis, for extracorporeal hemorheotherapy. Safety and efficacy of Rheopheresis for wound healing and skin oxygenation were investigated in patients with ischemic diabetic foot syndrome. Eight patients with type 2 diabetes mellitus and non-healing foot ulcers caused by severe ischemic diabetic foot syndrome were treated by a series of seven Rheopheresis sessions in a time span of 11 weeks. Wound healing had not been detectable under conditions of standardized wound care during at least 2 months. Wound status was classified by its morphology, severity and location, according to the criteria of Wagner. Transcutaneous oxygen pressure (tcPO2), laser Doppler flowmetry and vital capillary microscopy were repeatedly performed to monitor the effects of the Rheopheresis treatment series on microcirculation and skin blood flow. Laboratory parameters of blood rheology, endothelial function and inflammatory state were measured in addition to safety parameters. In four patients (baseline Wagner stage 2), Rheopheresis accelerated wound healing of foot ulcers and was associated with an improvement of Wagner stage and a pronounced increase in tcPO2. In two patients (baseline Wagner stage 2), wound healing was unchanged but mean tcPO2 increased, allowing successful minor amputation. Values of tcPO2 remained stable and enhanced for the 3 months follow-up period. In two patients (baseline Wagner stage 4 or 5), no improvements in foot lesions were observed within the treatment period. As an adjunct therapeutic option, Rheopheresis may preserve a functional lower extremity, delay amputation or reduce the extent of amputation.     

Non-occlusive mesenteric ischemia: etiology, diagnosis, and interventional therapy

Non-occlusive mesenteric ischemia (NOMI) compromises all forms of mesenteric ischemia with patent mesenteric arteries. It generally affects patients over 50 years of age suffering from myocardial infarction, congestive heart failure, aortic insufficiency, renal or hepatic disease and patients following cardiac surgery. Non-occlusive disease accounts for 20-30% of all cases of acute mesenteric ischemia with a mortality rate of the order of 50%. Acute abdominal pain may be the only early presenting symptom of mesenteric ischemia. Non-invasive imaging modalities, such as CT, MRI, and ultrasound, are able to evaluate the aorta and the origins of splanchnic arteries. Despite the technical evolution of those methods, selective angiography of mesenteric arteries is still the gold standard in diagnosing peripheral splanchnic vessel disease. In early non-occlusive mesenteric ischemia, as opposed to occlusive disease, there is no surgical therapy. It is known that mesenteric vasospasm persists even after correction of the precipitating event. Vasospasm frequently responds to direct intra-arterial vasodilator therapy, which is the only treatment that has been shown to be effective.     

Distinct basal ganglia hyperechogenicity in idiopathic basal ganglia calcification

We report a 67‐year‐old patient with idiopathic basal ganglia calcification (IBGC). He presented with progressive cognitive impairment, frontal lobe dysfunction, mild leg spasticity, and levodopa (L ‐dopa)‐responsive parkinsonism. Transcranial sonography (TCS) revealed marked hyperechogenicity of the basal ganglia and periventricular spaces bilaterally. The detected signal alterations showed a fairly symmetric distribution and corresponded to the hyperintense calcifications depicted on the computer tomography brain scan. The combination of symmetric hyperechogenic areas adjacent to the lateral ventricles and of the basal ganglia may serve as an imaging marker characteristic of IBGC. Hyperechogenicity due to extended basal ganglia calcification as presented here is distinct from the pattern of hyperechogenicity caused by heavy metal accumulation, which is described to be less striking. In addition to atypical parkinsonian syndromes such as progressive supranuclear palsy and multiple system atrophy, IBGC is thus another differential diagnosis of parkinsonism with basal ganglia hyperechogenicity. © 2010 Movement Disorder Society.     

Intranasal immunization of Balb/c mice against prion protein attenuates orally acquired transmissible spongiform encephalopathy

To test whether prion protein (PrP) specific secretory immunoglobulin A (sIgA) can be induced and protect against oral transmission of spongiform encephalopathy (SE) we immunized Balb/c mice either intragastrically or intranasally (i.n.) with a recombinant PrP-fragment (PrP90-231) and cholera toxin (CT) adjuvant. Since PrP90-231 was rapidly digested in intestinal lavage, aprotinin was added to some vaccine formulations. While an anti-CT response was elicited via both routes, solely i.n. immunization without aprotinin induced PrP-specific sIgA. They recognize predominantly PrP-oligomers as the antigen was aggregated in the vaccine formulations. Challenge experiments showed that the immune response induced by our protocol could not prevent disease, but increases the median survival of the animals. We conclude that PrP-specific sIgA reduce the infectivity of the inoculum and that complete protection against transmission of SE should be achievable by optimized immunization regimens.     

ABO-incompatible kidney transplantation of an 8-yr-old girl with donor/recipient-constellation A1B/B

BACKGROUND: Antigen-specific immunoadsorption combined with rituximab offers the possibility for ABO-incompatible kidney transplantation without splenectomy. PATIENT AND METHOD: An 8-year-old mentally retarded girl with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis due to mitochondriopathy poorly tolerated hemodialysis. Paternal blood group A1B was incompatible with blood group B of the child. Therefore, we decided to perform the first ABO-incompatible renal transplantation in a child in Germany using antigen-specific immunoadsorption. Rituximab (1 x 375 mg/m2) was administered 2 weeks before the first immunoadsorption (Glycosorb) ABO A-column). Triple-drug immunosuppression (tacrolimus, mycophenolate mofetil and prednisolone) was simultaneously started with immunoadsorption. Initial tacrolimus levels were targeted between 15 and 20 ng/ml. Before transplantation, six immunoadsorptions were applied on days -9, -7, -4, -3, -2 and -1. Intravenous immunoglobulin (0.5 g/kg) was administered preoperatively. After transplantation, three immunoadsorptions were performed on days +4, +6 and +8. RESULTS: Before transplantation, antibody (Ab) titers against paternal erythrocytes (20 degrees C) were reduced from 1 : 64 to 1 : 4 by six antigen-specific immunoadsorptions. After transplantation, we performed three more immunoadsorptions and the Ab titers were stable between 1 : 1 and 1 : 8. One, 2 and 8 months later we observed increases in the Ab titer up to 1 : 32 requiring no change in immunosuppressive therapy. No side effects of immunoadsorption were observed. The girl had excellent initial graft function with a serum creatinine of 55 to 70 micromol/l. Two weeks after transplantation, graft biopsy showed no signs of rejection; there was focal positivity for C4d only. Twelve months after transplantation, renal function was stable, with a serum creatinine of 117 micromol/l. Episodes of rejection or severe infections were absent. CONCLUSION: ABO-incompatible transplantation using antigen-specific immunoadsorption and rituximab may serve as a suitable alternative for children urgently needing renal transplantation and missing a blood group-compatible donor.     

MRI of the eye muscles in a case of ophthalmoplegia caused by common carotid artery occlusion suggests ischemic myopathy

Ocular muscle palsies following carotid artery disease is thought to be caused by ischemia of the cranial oculomotor nerves but it may also be due to ischemia of the extraocular muscles (EOM). We studied a patient with common carotid artery occlusion syndrome (CCAOS) to elucidate the two competing hypotheses. MRI and sonography of the orbita showed oedematous swelling of all left EOM. MRI short-tau inversion recovery (STIR) sequences showed hyperintensities and a prolonged T2-relaxation time in EOM indicating muscle oedema. It decreased within two weeks as ophthalmoplegia improved. For several reasons ischemic EOM myopathy rather than ischemic neuropathy seems to be the morphological correlate of ophthalmoplegia after ipsilateral CCAOS in this patient.