COVID-19 in Kidney Transplant Patients From a Large UK Transplant Center: Exploring Risk Factors for Disease Severity

BackgroundThe novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised concern for the health of immunocompromised individuals, who are potentially at higher risk of more severe infection and poorer outcomes. As a large London transplant center serving a diverse patient population, we report the outcomes of SARS-CoV-2 infection in our cohort of 2848 kidney and/or pancreas transplant patients.MethodsData were obtained retrospectively for all transplant patients who attended hospital during the peak of the pandemic and had a positive nasopharyngeal SARS-CoV-2 test.ResultsSixty-six patients were found to be positive for SARS-CoV-2. Twenty percent were treated as outpatients, 59% were admitted to the general ward, and 21% required intensive care. Treatment consisted of reduced immunosuppression, antibiotics for pneumonia or sepsis, and other supportive treatments. Within our cohort, 12 patients died (18%), with an overall mortality of 0.4%. Predictive risk factors for COVID-19 severity were explored.ConclusionsSevere disease was associated with lower hemoglobin prior to COVID-19 diagnosis and lower lymphocyte count at the time of diagnosis but not age, sex, ethnicity, or preexisting comorbidities. Lower glomerular filtration rate and higher C-reactive protein were associated with more severe disease. Despite no use of hydroxychloroquine, azithromycin, antiviral, or immunomodulatory medications, our mortality rate (kidney and pancreas transplant patients) is similar to current international rates.     

Impact of histology on survival in retroperitoneal sarcomas

Background

The current American Joint Committee on Cancer AJCC staging system applies to all soft-tissue sarcomas and does not allow for consideration of many features unique to retroperitoneal sarcomas (RPSs). The aim of this study was to analyze factors predictive of recurrence and survival for patients with resected RPSs.

Methods

This was a retrospective analysis of consecutive patients with primary RPS who underwent resection. A 3-tiered histological classification was examined: atypical lipomatous tumors (ALTs), non-ALT liposarcomas (LPSs), and other. Univariate and multivariate analyses were used to identify factors associated with differences in disease-free survival (DFS) and overall survival (OS) among groups.

Results

Sixty RPS patients were analyzed: 16 patients (27%) had ALTs, 7 patients (12%) had LPSs, and 37 patients (62%) had other histologies. A comparison of the 3 groups showed a significant difference in OS among groups (P < .017). High-grade tumors favored shorter DFS (P = .06) but were not associated with decreased OS when compared with low-grade tumors (P = .86).

Conclusions

These findings support an alternative staging system for RPS, inclusive of histology, which may prove useful in operative planning and prognostication.     

Associations of nadir haemoglobin level and red blood cell transfusion with mortality and length of stay in surgical specialties: a retrospective cohort study

Few studies have investigated if, and how, red cell transfusion and anaemia interact. We analysed 60,955 admissions to three metropolitan hospitals in Western Australia between 2008 and 2017 to determine whether the relationship between red cell transfusion and outcomes in surgical patients differed by lowest (nadir) level of haemoglobin. At levels above 100 g.l⁻¹, in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratios (ORs) (95%CI) being 8.80 (4.43–17.45) p < 0.001 and 3.68 (1.93–7.02) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.83 (1.28–2.61) p = 0.001, respectively. Likewise, between 90 g.l⁻¹ and 99 g.l⁻¹, in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratio (95%CI) being 3.76 (2.23–6.34) p < 0.001 and 1.96 (1.23–3.12) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.34 (1.05–1.70) p = 0.017, respectively. Length of stay was longer with transfusion at nadir haemoglobin levels above 100 g.l⁻¹ and in the following ranges: 90–99 g.l⁻¹, 80–89 g.l⁻¹, 70–79 g.l⁻¹ and 60–69 g.l⁻¹, the adjusted rate ratio (95%CI) being 1.38 (1.25–1.53) p < 0.001, 1.18 (1.10–1.27) p < 0.001, 1.17 (1.13–1.22) p < 0.001, 1.07 (1.02–1.12) p = 0.003 and 1.24 (1.13–1.36) p < 0.001, respectively. Mortality was higher with red cell transfusion at haemoglobin levels greater than 90 g.l⁻¹, whereas at all levels below 90 g.l⁻¹ mortality was not significantly higher or lower. Length of stay was longer with transfusion at nadir haemoglobin levels of 60 g.l⁻¹ or above. Our results suggest that nadir haemoglobin modified the relationship between red cell transfusion and outcomes and adds to the evidence recommending caution before transfusing red cells.     

Frontotemporal dementia: clinicopathological correlations

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) is characterized by impairments in social, behavioral, and/or language function, but postmortem studies indicate that multiple neuropathological entities lead to FTLD. This study assessed whether specific clinical features predict the underlying pathology. METHODS: A clinicopathological correlation was performed on 90 consecutive patients with a pathological diagnosis of frontotemporal dementia and was compared with an additional 24 cases accrued during the same time period with a clinical diagnosis of FTLD, but with pathology not typically associated with frontotemporal dementia. RESULTS: Postmortem examination showed multiple pathologies including tauopathies (46%), FTLD with ubiquitin-positive inclusions (29%), and Alzheimer's disease (17%). The pathological groups manifested some distinct demographic, clinical, and neuropsychological features, although these attributes showed only a statistical association with the underlying pathology. FTLD with ubiquitin-positive inclusions was more likely to present with both social and language dysfunction, and motor neuron disease was more likely to emerge in these patients. Tauopathies were more commonly associated with an extrapyramidal disorder. Alzheimer's disease was associated with relatively greater deficits in memory and executive function. INTERPRETATION: Clinical and neuropsychological features contribute to delineating the spectrum of pathology underlying a patient diagnosed with FTLD, but biomarkers are needed that, together with the clinical phenotype, can predict the underlying neuropathology.     

Substance P and vasoactive intestinal peptide are reduced in right transverse colon in pediatric slow‐transit constipation

Background Slow‐transit constipation (STC) is recognized in children but the etiology is unknown. Abnormalities in substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide (NO) have been implicated. The density of nerve fibers in circular muscle containing these transmitters was examined in colon from children with STC and compared to other pediatric and adult samples. Methods Fluorescence immunohistochemistry using antibodies to NO synthase (NOS), VIP and SP was performed on colonic biopsies (transverse and sigmoid colon) from 33 adults with colorectal cancer, 11 children with normal colonic transit and anorectal retention (NAR) and 51 with chronic constipation and slow motility in the proximal colon (STC). The percentage area of nerve fibers in circular muscle containing each transmitter was quantified in confocal images. Key Results In colon circular muscle, the percentage area of nerve fibers containing NOS > VIP > SP (6 : 2 : 1). Pediatric groups had a higher density of nerve fibers than adults. In pediatric samples, there were no regional differences in NOS and VIP, while SP nerve fiber density was higher in sigmoid than proximal colon. STC children had lower SP and VIP nerve fiber density in the proximal colon than NAR children. Twenty‐three percent of STC children had low SP nerve fiber density. Conclusions & Inferences There are age‐related reductions in nerve fiber density in human colon circular muscle. NOS and VIP do not show regional variations, while SP nerve fiber density is higher in distal colon. 1/3 of pediatric STC patients have low SP or VIP nerve fiber density in proximal colon.     

Gene expression studies in cultured dendritic cells: new indicators for the discrimination of skin sensitizers and irritants in vitro

Background The replacement of animal tests for the detection of the sensitizing potential of chemicals is of great importance due to current legislation. One promising approach for the development of an in vitro assay is the exposure of immature dendritic cells (iDCs) to contact sensitizers and irritants, followed by an analysis of the maturation status of the cells.
Objective The aim of this study was to further investigate the performance of our previously developed targeted microarray, the immune toxicity chip . In addition, we aimed to identify new marker genes for the discrimination of allergens and irritants using whole-genome microarrays.
Methods Monocyte-derived iDCs were exposed to contact sensitizers and irritants in concentrations resulting in 10–20% cytotoxicity, as determined by dose–response curves. Changes in gene expression were analysed using the immune toxicity chip and a commercially available whole-genome microarray.
Results Using the immune toxicity chip , we could identify a panel of marker genes suitable to discriminate strong allergens and irritants. Analysis with the whole-genome array revealed additional genes that are differentially expressed after allergen exposure, but not after irritant exposure. Hierarchical clustering of these genes showed distinct groups representing the different chemicals.
Conclusion Here we show that our test system based on an immune-specific microarray is suitable for the discrimination of strong allergens and irritants. Genes detected as differentially expressed with the whole-genome array and previously not connected to the maturation process of DCs might be suitable candidate genes for the identification of weaker sensitizers.     

Catatonia with schizophrenia: From ECT to rTMS

Background

Electroconvulsive therapy is indicated in cases of catatonic schizophrenia following a failure of the challenge test with lorazepam or Zolpidem^®. Some patients need maintenance treatment with ECT. Repetitive Transcranial Magnetic Stimulation (rTMS) and anodal Transcranial direct-current stimulation (tDCS) might be effective against catatonia.