Human Kidney Spheroids and Monolayers Provide Insights into SARS-CoV-2 Renal Interactions.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) causes significan t morbidity, mainly from pulmonary involvement, extrapulmonary symptoms are also major componen ts of the disease. Kidney disease, usually presenting as AKI, is particularly severe among patients with COVID-19. It is unknown, however, whether such injury results from direct kidney infection with COVID-19's causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or from indirect mechanisms. METHODS: Using ex vivo cell models, we sought to analyze SARS-CoV-2 interactions with kidney tubular cells and assess direct tubular injury. These models comprised primary human kidney epithelial cells (derived from nephrectomies) and grown as either proliferating monolayers or quiescent three-dimensional kidney spheroids. RESULTS: We demonstrated that viral entry molecules and high baseline levels of type 1 IFN-related molecules were present in monolayers and kidney spheroids. Although both models support viral infection and replication, they did not exhibit a cytopathic effect and cell death, outcomes that were strongly present in SARS-CoV-2-infected controls (African green monkey kidney clone E6 [Vero E6] cultures). A comparison of monolayer and spheroid cultures demonstrated higher infectivity and replication of SARS-CoV-2 in actively proliferating monolayers, although the spheroid cultures exhibited high er levels of ACE2. Monolayers exhibited elevation of some tubular injury molecules-including molecules related to fibrosis (COL1A1 and STAT6) and dedifferentiation (SNAI2)-and a loss of cell identity, evident by reduction in megalin (LRP2). The three-dimensional spheroids were less prone to such injury. CONCLUSIONS: SARS-CoV-2 can infect kidney cells without a cytopathic effect. AKI-induced cellular proliferation may potentially intensify infectivity and tubular damage by SARS-CoV-2, suggesting that early intervention in AKI is warranted to help minimize kidney infection.

Polyneuropathy, Myocardial Dysfunction and Pericardial Effusion Following Duodenal Switch.

Duodenal Switch procedure is a type of bariatric surgery that was reserved for severely morbid obese people. Patients undergoing this procedure are at high risk for nutrient deficiencies. In this report we present a case of a patient who had developed polyneuropathy, generalized muscle weakness, Wernicke encephalopathy, myocardial dysfunction and pericardial effusion six years following this operation. He was treated by multivitamins and trace elements with a complete resolution of all of these disturbances. The patient was fully rehabilitated.

Diabetes detection from non-diabetic retinopathy fundus images using deep learning methodology.

Diabetes is one of the leading causes of morbidity and mortality in the United States and worldwide. Traditionally, diabetes detection from retinal images has been performed only using relevant retinopathy indications. This research aimed to develop an artificial intelligence (AI) machine learning model which can detect the presence of diabetes from fundus imagery of eyes without any diabetic eye disease. A machine learning algorithm was trained on the EyePACS dataset, consisting of 47,076 images. Patients were also divided into cohorts based on disease duration, each cohort consisting of patients diagnosed within the timeframe in question (e.g., 15 years) and healthy participants. The algorithm achieved 0.86 area under receiver operating curve (AUC) in detecting diabetes per patient visit when averaged across camera models, and AUC 0.83 on the task of detecting diabetes per image. The results suggest that diabetes may be diagnosed non-invasively using fundus imagery alone. This may enable diabetes diagnosis at point of care, as well as other, accessible venues, facilitating the diagnosis of many undiagnosed people with diabetes.

Bone mineral density of the ultra-distal radius: are we ignoring valuable information?

The current study explored the possible utilization in dual-X-ray-absorptiometry scanning (DXA) of the ultra-distal radius (UDR). This region of interest is currently unused and mostly unstudied in this context. The study findings suggest UDR as potential useful region of interest in DXA scanning and warrant further study of the site. PURPOSE: Bone mineral density (BMD) measurement of a non-dominant arm is not routinely performed during dual-X-ray-absorptiometry (DXA) test, and the possible utility of ultra-distal (UDR) radius BMD is not well-studied. We evaluated in women, correlations of UDR BMD with fracture prevalence, fracture risk prediction by the fracture risk assessment tool (FRAX), and osteoporosis diagnosed by traditional sites. METHODS: Women who underwent a routine DXA (including their non-dominant forearm and including UDR BMD) in a tertiary medical center were included. Risk factors relevant to FRAX calculation were assessed via a self-administered questionnaire. Spearman correlations of UDR BMD to 10-year risks of major osteoporotic and hip fractures (assessed by FRAX) were explored. The possible added value of UDR BMD in explaining prevalent osteoporotic fractures was assessed using a multivariable regression model incorporating age and traditional osteoporosis diagnosis. RESULTS: The study included 1245 women with a median age of 66 years (interquartile range: 59-73), of whom 298 (24%) had UDR T-score ≤ - 2.5 and 154 (12%) reported prior fractures. UDR BMD was significantly negatively correlated with FRAX risk score for hip and major osteoporotic fractures (R = - 0.5 and R = - 0.41, respectively; P < 0.001). UDR T-score ≤ - 2.5 was associated with higher fracture prevalence (19% vs 10%; P < 0.001) and remained significant after adjusting for traditional BMD and age (OR 1.49, 1.01-2.19; P = 0.043). CONCLUSION: UDR BMD correlates both with prior fractures and with predicted fracture risks and might pose added value over traditional DXA sites.