COVID-19 among workers assisting homeless and socially vulnerable people

ABSTRACT Objective To describe the profile of professionals assisting homeless and socially vulnerable populations tested for COVID-19, and to determine potential associations with exposure at the workplace, on the way to work, or at home, among infected professionals. To describe disease symptoms and progression and to investigate potential associations with age, sex and exposure at the workplace, on the way to work, or at home. Methods A retrospective analysis of data of 173 workers employed by Serviço Franciscano de Solidariedade tested for SARS-CoV-2. Between May 20 and June 2, 2020, professionals and volunteers were tested for anti-SARS-CoV-2 IgG and IgM antibodies, by means of qualitative rapid chromatographic immunoassay in whole blood. A questionnaire was used to collect data on demographic characteristics and working conditions, history and date of onset of symptoms and risk factors. Quantitative variables were expressed as mean and standard deviation, or median, maximum, and minimum values. Data normality was investigated using the Kolmogorov-Smirnov test. Results A total of 46 (26.6%) participants had positive serologic tests. Of participants with negative serologic test results, 109 (85.8%) were asymptomatic. History of symptoms was the most significant independent factor associated with positive serology. Serologic test results and symptoms differed significantly according to housing (p=0.045) and working (p<0.001) conditions. More than half of participants (52.4%) living in shared households tested positive, compared to 23% of participants living in family households. Participants working remotely from home did not test positive. In seropositive participants, onset of symptoms was associated with workplace exposure and shared housing conditions. Conclusion History of symptoms was associated with positive serology for COVID-19. Shared housing conditions tended to be associated with higher risk of infection. Onset of symptoms was associated with higher levels of workplace exposure and shared housing conditions in seropositive participants.

Development and Field Validation of Lidocaine-Loaded Castration Bands for Bovine Pain Mitigation.

Castration is among the most common management procedures performed in the dairy and beef cattle industries and is mainly performed by surgery or elastic banding. Despite the various benefits of castration, all methods produce pain and distress. Castration by banding is simple, inexpensive, produces fewer complications, and can be performed in a high-throughput manner. Because lidocaine, a local anesthetic, can be delivered to trauma sites topically, we have formulated lidocaine-loaded castration bands (LLBs) to deliver local pain relief to calves during banded castration. The initial lidocaine content of three band types developed was between 80 and 200 mg per band. The transfer kinetics of lidocaine into tissue was determined in vitro, indicating a rapid release for the first 30 min, followed by a slow release lasting at least 48 h. Furthermore, the lidocaine delivery and pain mitigation effects of these LLBs were compared to standard lidocaine injections in vivo. Field studies indicated that LLBs performed at least as well as lidocaine injections for short-term lidocaine delivery into tissues and pain mitigation. Moreover, LLBs significantly outperformed lidocaine injections for long-term delivery and pain mitigation. The concentrations of lidocaine in the LLB-treated tissue samples were generally in the range of 0.5-3.5 mg of lidocaine per gram of tissue and were overall highest after 6 h. Lidocaine-loaded elastration bands deliver therapeutic quantities of lidocaine into scrotal tissues over a period of at least seven days in cattle. This approach would provide long-term pain mitigation to the animals and, by avoiding surgery or the administration of injections, would also decrease the time and handling costs for the producer.

Rate of growth-A novel surrogate marker for high-risk cutaneous squamous cell carcinoma? A case report and review of the literature.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common nonmelanoma skin cancer worldwilde, with a more invasive growth pattern and higher potential to metastatize than basal cell carcinoma. Although several risk factors have been linked to a high metastatic potential of cSCC, no widely accepted classification system for this common subtype of cancer exists. Herein we report an emblematic case of rapidly growing and metastatic cSCC and discuss the rate of growth of the tumour (ROG) as novel prognostic high risk surrogate marker.

Hypomelanotic melanoma detected by the "little red riding hood sign" in a patient with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a genetic disorder commonly associated with an increased risk for development of malignancy, including skin cancers. Herein we describe a case of invasive melanoma occurring in a patient with NF1 and discuss the association between these two diseases, highlighting the importance of comparative clinical and dermoscopic approaches in this category of patients in which the detection of melanoma can be difficult because of the presence of multiple skin tumors.

Acute Renal Graft-Versus-Host Disease in a Murine Model of Allogeneic Bone Marrow Transplantation.

Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and is associated with a poor prognosis. Generally, the kidneys are assumed to not be no direct targets of graft-versus-host disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully major histocompatibility complex (MHC)-mismatched model of BALB/c mice conditioned and transplanted according to 2 different intensity protocols. Syngeneically transplanted and untreated animals served as controls. Four weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-d-glucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T cells consisted of CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (tumor necrosis factor α, interferon-γ, interleukin 1 α [IL-1α], IL-2, IL-6, and IL-10), and adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cell-mediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal impairment.

Vascular Alterations in a Murine Model of Acute Graft-Versus-Host Disease Are Associated with Decreased Serum Levels of Adiponectin and an Increased Activity and Vascular Expression of Indoleamine 2,3-Dioxygenase.

Graft-versus-host disease (GVHD) is the limiting complication after bone marrow transplantation (BMT), and its pathophysiology seems to be highly influenced by vascular factors. Our study aimed at elucidating possible mechanisms involved in vascular GVHD. For this purpose, we used a fully MHC-mismatched model of BALB/c mice conditioned according to two different intensity protocols with total body irradiation and transplantation of allogeneic (C57BL/6) or syngeneic bone marrow cells and splenocytes. Mesenteric resistance arteries were studied in a pressurized myograph. We also quantified the expression of indoleamine 2,3-dioxygenase (IDO), endothelial (eNOS), and inducible NO synthase (iNOS), as well as several pro- and anti-inflammatory cytokines. We measured the serum levels of tryptophan (trp) and kynurenine (kyn), the kyn/trp ratio (KTR) as a marker of IDO activity, and adiponectin (APN). The myographic study showed a correlation of GVHD severity after allogeneic BMT with functional vessel alterations that started with increased vessel stress and ended in eccentric vessel remodeling, increased vessel strain, and endothelial dysfunction. These alterations were accompanied by increasing IDO activity and decreasing APN levels in the serum of allogeneic animals. The mRNA expression showed significantly elevated IDO, decreased eNOS, and elevation of most studied pro- and anti-inflammatory cytokines. Our study provides further data supporting the importance of vessel alterations in GVHD and is the first to show an association of vascular GVHD with hypoadiponectinemia and an increased activity and vascular expression of IDO. Whether there is also a causative involvement of these two factors in the development of GVHD needs to be further investigated.

Telomere shortening in enterocytes of patients with uncontrolled acute intestinal graft-versus-host disease.

Acute intestinal graft-versus-host disease (aGVHD) refractory to immunosuppressive treatment is a serious complication after allogenic hematopoietic stem cell transplantation (HSCT). The underlying mechanisms of refractory aGVHD of the gut are not fully understood. Although telomere length (TL) reflects the replicative history of a cell, critically short telomeres have been associated with replicative exhaustion and tissue failure. In this study, we demonstrate that enterocytes of patients with refractory intestinal aGVHD show significantly increased proliferation, which translates into significant and critical telomere attrition following HSCT as compared with unaffected patients undergoing HSCT. Calculated telomere loss in aGVHD patients is 190 bp/wk, thereby massively exceeding physiological steady-state TL shortening rates such as in lymphocytes (∼50 bp/y). Our data support the hypothesis that increased compensatory proliferation following continued tissue damage can result in massive telomere loss in enterocytes of aGVHD patients. The present study introduces aGVHD-triggered increased cellular turnover and telomere loss with subsequent replicative exhaustion as a mechanism for refractory gut GVHD that is compatible with the long-term clinical aspect of the disease and provides a basis for stem cell protective therapies in the treatment of aGVHD.

Autophagy gene Atg16L1 prevents lethal T cell alloreactivity mediated by dendritic cells.

Atg16L1 mediates the cellular degradative process of autophagy and is considered a critical regulator of inflammation based on its genetic association with inflammatory bowel disease. Here we find that Atg16L1 deficiency leads to an exacerbated graft-versus-host disease (GVHD) in a mouse model of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Atg16L1-deficient allo-HSCT recipients with GVHD displayed increased T cell proliferation due to increased dendritic cell (DC) numbers and costimulatory molecule expression. Reduced autophagy within DCs was associated with lysosomal abnormalities and decreased amounts of A20, a negative regulator of DC activation. These results broaden the function of Atg16L1 and the autophagy pathway to include a role in limiting a DC-mediated response during inflammatory disease, such as GVHD.

Endothelial dysfunction and altered mechanical and structural properties of resistance arteries in a murine model of graft-versus-host disease.

A putative involvement of the vasculature seems to play a critical role in the pathophysiology of graft-versus-host disease (GVHD). We aimed to characterize alterations of mesenteric resistance arteries in GVHD in a fully MHC-mismatched model of BALB/c mice conditioned with total body irradiation that underwent transplantation with bone marrow cells and splenocytes from syngeneic (BALB/c) or allogeneic (C57BL/6) donors. After 4 weeks, animals were sacrificed and mesenteric resistance arteries were studied in a pressurized myograph. The expression of endothelial (eNOS) and inducible nitric oxide (NO)-synthase (iNOS) was quantified and vessel wall ultrastructure was investigated with electron microscopy. The myograph study revealed an endothelial dysfunction in allogeneic-transplant recipients, whereas endothelium-independent vasodilation was similar to syngeneic-transplant recipients or untreated controls. The expression of eNOS was decreased and iNOS increased, possibly contributing to endothelial dysfunction. Additionally, arteries of allogeneic transplant recipients exhibited a geometry-independent increase in vessels strain. For both findings, electron microscopy provided a structural correlate by showing severe damage of the whole vessel wall in allogeneic-transplant recipient animals. Our study provides further data to prove, and is the first to characterize, functional and structural vascular alterations in the early course after allogeneic transplantation directly in an ex vivo setting and, therefore, strongly supports the hypothesis of a vascular form of GVHD.

Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease.

Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 µmol/L to 11.8 ± 2.8 µmol/L in all post-transplant samples and to 3.5 ± 3 µmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT.

Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: a progression model.

BACKGROUND: Little is known about the dermoscopic features of keratinocyte skin cancer. OBJECTIVE: We sought to determine the dermoscopic features of facial actinic keratosis (AK), intraepidermal carcinoma (IEC), moderately to poorly differentiated invasive squamous cell carcinoma (SCC), and well-differentiated SCC of the keratoacanthoma type. METHODS: This was a retrospective analysis of dermoscopic images of histopathologically diagnosed keratinocyte skin cancer. RESULTS: A total of 243 (70 AK, 71 IEC, 78 SCC, and 24 keratoacanthomas) tumors of the face from 243 patients (mean age: 71.1 years; range: 44-94 years) were analyzed. The majority of patients had a fair skin type, history of melanoma or nonmelanoma skin cancer, and multiple AK. A red pseudonetwork was significantly associated with AK (P < .001), whereas dotted/glomerular vessels, diffuse yellow opaque scales, and microerosions were significantly more prevalent among IEC (P < .001). Hairpin vessels, linear-irregular vessels, targetoid hair follicles, white structureless areas, a central mass of keratin, and ulceration were significantly associated with invasive SCC (P < .001 for all criteria). Similar patterns as in SCC were observed among keratoacanthomas. LIMITATIONS: The retrospective design of our study and the lack of assessment of sensitivity and specificity of the dermoscopic criteria are limitations. CONCLUSIONS: Based on our findings we propose a progression model of facial AK developing into IEC and invasive SCC.

Frequency of dermoscopic nevus subtypes by age and body site: a cross-sectional study.

OBJECTIVE: To subclassify acquired nevi by dermoscopic pattern. DESIGN: Cross-sectional study with consecutive enrollment. SETTING: Pigmented lesion clinics in referral academic medical centers. PARTICIPANTS: Individuals older than 2 years undergoing total skin examination were consecutively recruited between October 1, 2008, and May 31, 2009, and, based on their age, assigned to 1 of 8 groups. For each patient, the location and dermoscopic pattern of all nevi on the torso were recorded. Nevi were dermoscopically subclassified as globular, reticular, mixed (reticular-globular) pattern with peripheral or central globules, or unspecified pattern. MAIN OUTCOME MEASURE: Frequency of dermoscopic nevus subtypes stratified by patient age and location of the nevi. RESULTS: A total of 5481 nevi in 480 individuals were evaluated. The number of all nevus subgroups, except for unspecified pattern nevi, significantly increased before and decreased after the fourth decade of life. Globular nevi were most prevalent on the upper trunk in children and adolescents; the number decreased consistently after the second decade of life. The reticular pattern was the most common nevus pattern after the second decade of life and the most common nevus subgroup on the upper and middle back. Although uncommon, central globular nevi also showed an age-dependent trend, similar to that of reticular nevi. Nevi with the peripheral globular pattern declined rapidly after the third decade of life and were no longer observed after the sixth decade. The number of unspecified pattern nevi was stable across all age groups. CONCLUSION: Age, dermoscopic pattern, and location of nevi should be jointly considered when evaluating melanocytic lesions.