Epicardial adipose tissue characteristics, obesity and clinical outcomes in COVID-19: A post-hoc analysis of a prospective cohort study.

BACKGROUND AND AIMS: Obesity-related cardiometabolic risk factors associate with COVID-19 severity and outcomes. Epicardial adipose tissue (EAT) is associated with cardiometabolic disturbances, is a source of proinflammatory cytokines and a marker of visceral adiposity. We investigated the relation between EAT characteristics and outcomes in COVID-19 patients. METHODS AND RESULTS: This post-hoc analysis of a large prospective investigation included all adult patients (≥18 years) admitted to San Raffaele University Hospital in Milan, Italy, from February 25th to April 19th, 2020 with confirmed SARS-CoV-2 infection who underwent a chest computed tomography (CT) scan for COVID-19 pneumonia and had anthropometric data available for analyses. EAT volume and attenuation (EAT-At, a marker of EAT inflammation) were measured on CT scan. Primary outcome was critical illness, defined as admission to intensive care unit (ICU), invasive ventilation or death. Cox regression and regression tree analyses were used to assess the relationship between clinical variables, EAT characteristics and critical illness. One-hundred and ninety-two patients were included (median [25th-75th percentile] age 60 years [53-70], 76% men). Co-morbidities included overweight/obesity (70%), arterial hypertension (40%), and diabetes (16%). At multivariable Cox regression analysis, EAT-At (HR 1.12 [1.04-1.21]) independently predicted critical illness, while increasing PaO2/FiO2 was protective (HR 0.996 [95% CI 0.993; 1.00]). CRP, plasma glucose on admission, EAT-At and PaO2/FiO2 identified five risk groups that significantly differed with respect to time to death or admission to ICU (log-rank p < 0.0001). CONCLUSION: Increased EAT attenuation, a marker of EAT inflammation, but not obesity or EAT volume, predicts critical COVID-19. TRIAL REGISTRATION: NCT04318366.

Lung Ultrasound in COVID-19 A Role Beyond the Acute Phase?

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2. With the increasing number of improved and discharged patients with COVID-19, the definition of an adequate follow-up strategy is needed. The purpose of this study was to assess whether lung ultrasound (LUS) is an effective indicator of subclinical residual lung damage in patients with COVID-19 who meet discharge criteria. METHODS: We prospectively enrolled 70 consecutive patients with COVID-19 who had a prolonged hospitalization with inpatient rehabilitation between April 6 and May 22, 2020. All of the patients underwent an LUS evaluation at discharge. Data of patients with more severe disease during the acute phase (ie, required ventilatory support) were compared to those of patients with milder disease. RESULTS: Among the 70 patients with COVID-19 (22 women and 48 men; mean age ± SD, 68 ± 13 years), the LUS score before discharge was still frankly pathologic and higher in patients who had more severe disease during the acute phase compared to patients with milder disease (median [interquartile range], 8.0 [5.5-13.5] versus 2.0 [1.0-7.0]; P < .001), even when both categories met internationally defined discharge criteria. CONCLUSIONS: Lung ultrasound can identify the persistence of subclinical residual lung damage in patients with severe COVID-19 even if they meet discharge criteria. Considering the low cost, easy application, and lack of radiation exposure, LUS seems the ideal tool to be adopted in outpatient and primary care settings for the follow-up of patients with COVID-19.

Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial.

BACKGROUND: The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. METHODS: In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1-2 months (M) apart 4-18M posttransplant. Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post-dose 1, and 1M and 12M post-dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post-dose 2. RESULTS: Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post-dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups. CONCLUSIONS: RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose. CLINICAL TRIALS REGISTRATION: NCT02058589.

Management of metabolic alterations in adult kidney transplant recipients: A joint position statement of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID).

Chronic metabolic alterations such as post-transplant diabetes mellitus (PTDM), dyslipidaemias and overweight/obesity significantly impact on kidney transplant (KT) outcomes. This joint position statement is based on the evidence on the management of metabolic alterations in KT recipients (KTRs) published after the release of the 2009 KDIGO clinical practice guideline for the care of KTRs. Members of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID) selected to represent professionals involved in the management of KTRs undertook a systematic review of the published evidence for the management of PTDM, dyslipidaemias and obesity in this setting. The aim of this work is to provide an updated review of the evidence on the prevention, diagnosis and treatment of metabolic alterations in KTRs, in order to support physicians, patients and the Healthcare System in the decision-making process when choosing among the various available options.

Diabetes-free survival after extended distal pancreatectomy and islet auto transplantation for benign or borderline/malignant lesions of the pancreas.

Islet autotransplant is particularly attractive to prevent diabetes after extended pancreatectomy for benign or borderline/malignant pancreas disease. Between 2008 and 2018, 25 patients underwent left extended pancreatectomy (>60%) and islet autotransplant for a neoplasm located in the pancreatic neck or proximal body. Overall, disease-free and diabetes-free survivals were estimated and compared with those observed in 68 nondiabetic patients who underwent distal pancreatectomy for pancreatic neoplasms without islet autotransplant. Median follow-up was 4 years. We observed no deaths and a low morbidity (nonserious procedure-related complications in 2 of 25 patients). Patient and insulin-independent survival rates at 4 years were 100% and 96%, respectively. Glucose homeostasis remained within a nondiabetic range at all times for 19 (73%) of 25 patients. Preoperative glycemic level and insulin resistance were major predictors of diabetes development in these patients. Patients undergoing islet autotransplant had a longer diabetes-free survival than did patients without islet autotransplant (P = .04). In conclusion, islet autotransplant after extended pancreatic resection for neoplasms is a safe and successful procedure for preventing diabetes.

Islet Transplantation Alone Versus Solitary Pancreas Transplantation: an Outcome-Driven Choice?

PURPOSE OF REVIEW: In patients with type 1 diabetes with extreme glycemic variability, the restoration of pancreas endocrine function is potentially and completely achieved with islets of Langerhans (tissue derived from whole organ) or pancreas (whole organ) transplantation. The aim of our review is to report on the latest studies and to highlight the benefits and risks of the two procedures, providing clearer, more selective, evidence-based clinical indications that also consider the impact on the degenerative complications of diabetes as a potential benefit. RECENT FINDINGS: Clinical experience in this field has been dynamic over the last three decades, and has been characterized by the development of more standardized protocols and a clearer definition of clinical outcome. On the contrary, the recommendations thus far are not well delineated and tend to overlap, and the past ADA position statement for pancreas transplant alone has also been applied to islet transplant alone, without differentiation. Both outcome-driven and non-outcome-driven criteria are considered in the conclusions, in an attempt to streamline indications for islet-alone or pancreas-alone transplantation.

High Flow Nasal Cannula Oxygen vs. Conventional Oxygen Therapy and Noninvasive Ventilation in Emergency Department Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute respiratory failure (ARF) is a common cause of presentation to the Emergency Department (ED). High flow nasal cannula (HFNC) has been introduced as an alternative way to administer oxygen. OBJECTIVES: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing HFNC with conventional oxygen therapy (COT) and noninvasive ventilation (NIV) exclusively in the ED setting. METHODS: Inclusion criteria were: RCTs on adults with ARF admitted to the ED, investigating HFNC vs. COT or other modes of ventilation. Trials that compared HFNC support outside the ED, were published as an abstract, or nonrandomized were excluded. RESULTS: Four RCTs comparing HFNC with COT and one HFNC to NIV met the criteria. Overall, 775 patients were included. The meta-analysis of the studies comparing HFNC and COT showed no differences in intubation requirement, treatment failure, hospitalization, or mortality. Intolerance was significantly higher with HFNC (risk ratio 6.81 95% confidence interval 1.18-39.19; p = 0.03). In the only available RCT comparing HFNC with NIV, no difference was found for intubation rate, treatment failure, tolerance, and dyspnea. CONCLUSIONS: We did not find any benefit of HFNC compared with COT and NIV in terms of intubation requirement, treatment failure, hospitalization, and mortality; COT was better tolerated.

Renal Resistance Trend During Hypothermic Machine Perfusion Is More Predictive of Postoperative Outcome Than Biopsy Score: Preliminary Experience in 35 Consecutive Kidney Transplantations.

Hypothermic machine perfusion (HPM) grants a better postoperative outcome in transplantation of organs procured from extended criteria donors (ECDs) and donors after cardiac death (DCD). So far, the only available parameter for outcome prediction concerning those organs is pretransplant biopsy score. The aim of this study is to evaluate whether renal resistance (RR) trend during HPM may be used as a predictive marker for post-transplantation outcome. From December 2015 to present, HMP has been systematically applied to all organs from ECDs and DCD. All grafts underwent pretransplantation biopsy evaluation using Karpinski's histological score. Only organs that reached RR value ≤1.0 within 3 hours of perfusion were transplanted. Single kidney transplantation (SKT) or double kidney transplantation (DKT) were performed according to biopsy score results. Sixty-five HMPs were performed (58 from ECDs and 7 from DCD/ECMO donors). Fifteen kidneys were insufficiently reconditioned (RR > 1) and were therefore discarded. Forty-nine kidneys were transplanted, divided between 21 SKT and 14 DKT. Overall primary nonfunction (PNF) and delayed graft function (DGF) rate were 2.9 and 17.1%, respectively. DGF were more common in kidneys from DCD (67 vs. 7%; P = 0.004). Biopsy score did not correlate with PNF/DGF rate (P = 0.870) and postoperative creatinine trend (P = 0.796). Recipients of kidneys that reached RR ≤ 1.0 within 1 hour of HMP had a lower PNF/DGF rate (11 vs. 44%; P = 0.033) and faster serum creatinine decrease (POD10 creatinine: 1.79 mg/dL vs. 4.33 mg/dL; P = 0.019). RR trend is more predictive of post-transplantation outcome than biopsy score. Hence, RR trend should be taken into account in the pretransplantation evaluation of the organs.

Generation of donor-specific Tr1 cells to be used after kidney transplantation and definition of the timing of their in vivo infusion in the presence of immunosuppression.

BACKGROUND: Operational tolerance is an alternative to lifelong immunosuppression after transplantation. One strategy to achieve tolerance is by T regulatory cells. Safety and feasibility of a T regulatory type 1 (Tr1)-cell-based therapy to prevent graft versus host disease in patients with hematological malignancies has been already proven. We are now planning to perform a Tr1-cell-based therapy after kidney transplantation. METHODS: Upon tailoring the lab-grade protocol to patients on dialysis, aims of the current work were to develop a clinical-grade compatible protocol to generate a donor-specific Tr1-cell-enriched medicinal product (named T10 cells) and to test the Tr1-cell sensitivity to standard immunosuppression in vivo to define the best timing of cell infusion. RESULTS: We developed a medicinal product that was enriched in Tr1 cells, anergic to donor-cell stimulation, able to suppress proliferation upon donor- but not third-party stimulation in vitro, and stable upon cryopreservation. The protocol was reproducible upon up scaling to leukapheresis from patients on dialysis and was effective in yielding the expected number of T10 cells necessary for the planned infusions. The tolerogenic gene signature of circulating Tr1 cells was minimally compromised in kidney transplant recipients under standard immunosuppression and it eventually started to recover 36 weeks post-transplantation, providing rationale for selecting the timings of the cell infusions. CONCLUSIONS: These data provide solid ground for proceeding with the trial and establish robust rationale for defining the correct timing of cell infusion during concomitant immunosuppressive treatment.

Clinical results of islet transplantation.

Islet transplantation is considered an advanced therapy in the treatment of type-1 diabetes, with a progressive improvement of clinical results as seen in the Collaborative Islet Transplant Registry (CITR) report. It is an accepted method for the stabilization of frequent hypoglycemia, or severe glycemic lability, in patients with hypoglycemic unawareness, poor diabetic control, or a resistance to intensive insulin-based therapies. Worldwide data confirm a positive trend in this field, with the integrated management of pivotal factors: adequate islet mass, immunosuppressive protocols, additional anti-inflammatory therapy, and pre-transplant allo-immunity assessment. Insulin independence has been observed in several clinical trials with different rate, ranging 100-65% of patients; the maintenance of this condition during the follow-up progressively decreased, actually arranged on 44% 3 years after the last infusion, according to data reported from the CITR. Successful duration is progressively increasing, with ≥13 years being the longest reported insulin-free condition on record. The immediate results of functioning islet transplantation are an improvement in hypoglycemic awareness and a reduction in the glycated hemoglobin level. Furthermore, many studies have shown its influence on the chronic complications of diabetes, such as peripheral neuropathy, retinopathy, and macroangiopathy. Pre-transplant nephropathy remains an exclusion criterion as immunosuppressive therapy can exacerbate kidney-function deterioration. The problems linked to immunosuppression following islet transplantation for the treatment of type-1 diabetes need to be considered in order to achieve the correct risk/benefit ratio for each patient.

Novel immunological strategies for islet transplantation.

Islet transplantation has been demonstrated to improve glycometabolic control, to reduce hypoglycemic episodes and to halt the progression of diabetic complications. However, the exhaustion of islet function and the side effects related to chronic immunosuppression limit the spread of this technique. Consequently, new immunoregulatory protocols have been developed, with the aim to avoid the use of a life-time immunosuppression. Several approaches have been tested in preclinical models, and some are now under clinical evaluation. The development of new small molecules and new monoclonal or polyclonal antibodies is continuous and raises the possibility of targeting new costimulatory pathways or depleting particular cell types. The use of stem cells and regulatory T cells is underway to take advantage of their immunological properties and to induce tolerance. Xenograft islet transplantation, although having severe problems in terms of immunological compatibility, could theoretically provide an unlimited source of donors; using pigs carrying human immune antigens has showed indeed promising results. A completely different approach, the use of encapsulated islets, has been developed; synthetic structures are used to hide islet alloantigen from the immune system, thus preserving islet endocrine function. Once one of these strategies is demonstrated safe and effective, it will be possible to establish clinical islet transplantation as a treatment for patients with type 1 diabetes long before the onset of diabetic-related complications.

Hepatic steatosis after islet transplantation: Can ultrasound predict the clinical outcome? A longitudinal study in 108 patients.

Percutaneous intra-portal islet transplantation (PIPIT) is a less invasive, safer, and repeatable therapeutic option for brittle type 1 diabetes, compared to surgical pancreas transplantation. Hepatic steatosis is a consequence of the islet engraftment but it is curiously present in a limited number of patients and its meaning is controversial. The aims of this study were to assess hepatic steatosis at ultrasound (US) after PIPIT investigating its relationship with graft function and its role in predicting the clinical outcome. From 1996 to 2012, 108 patients underwent PIPIT: 83 type-1 diabetic patients underwent allo-transplantation, 25 auto-transplantation. US was performed at baseline, 6, 12, and 24 months, recording steatosis prevalence, first detection, duration, and distribution. Contemporaneously, steatotic and non-steatotic patients were compared for the following parameters: infused islet mass, insulin independence rate, ß-score, C-peptide, glycated hemoglobin, exogenous insulin requirement, and fasting plasma glucose. Steatosis at US was detected in 21/108 patients, 20/83 allo-transplanted and 1/25 auto-transplanted, mostly at 6 and 12 months. Infused islet mass was significantly higher in steatotic than non-steatotic patients (IE/kg: S=10.822; NS=6138; p=0.001). Metabolically, steatotic patients had worse basal conditions, but better islet function when steatosis was first detected, after which progressive islet exhaustion, along with steatosis disappearance, was observed. Conversely, in non-steatotic patients these parameters remained stable in time. Number of re-transplantations was significantly higher in steatotic than in non-steatotic patients (1.8 vs 1.1; p=0.001). Steatosis at US seems to be related to the islet mass and local overworking activity. It precedes metabolic alterations and can predict graft dysfunction addressing to therapeutic decisions before islet exhaustion. If steatosis does not appear, no conclusion can be drawn.

Rapamycin unbalances the polarization of human macrophages to M1.

Plasticity is a hallmark of macrophages, and in response to environmental signals these cells undergo different forms of polarized activation, the extremes of which are called classic (M1) and alternative (M2). Rapamycin (RAPA) is crucial for survival and functions of myeloid phagocytes, but its effects on macrophage polarization are not yet studied. To address this issue, human macrophages obtained from six normal blood donors were polarized to M1 or M2 in vitro by lipopolysaccharide plus interferon-γ or interleukin-4 (IL-4), respectively. The presence of RAPA (10 ng/ml) induced macrophage apoptosis in M2 but not in M1. Beyond the impact on survival in M2, RAPA reduced CXCR4, CD206 and CD209 expression and stem cell growth factor-ß, CCL18 and CCL13 release. In contrast, in M1 RAPA increased CD86 and CCR7 expression and IL-6, tumour necrosis factor-α and IL-1ß release but reduced CD206 and CD209 expression and IL-10, vascular endothelial growth factor and CCL18 release. In view of the in vitro data, we examined the in vivo effect of RAPA monotherapy (0·1 mg/kg/day) in 12 patients who were treated for at least 1 month before islet transplant. Cytokine release by Toll-like receptor 4-stimulated peripheral blood mononuclear cells showed a clear shift to an M1-like profile. Moreover, macrophage polarization 21 days after treatment showed a significant quantitative shift to M1. These results suggest a role of mammalian target of rapamycin (mTOR) into the molecular mechanisms of macrophage polarization and propose new therapeutic strategies for human M2-related diseases through mTOR inhibitor treatment.

Extending indications for islet autotransplantation in pancreatic surgery.

OBJECTIVE: To assess metabolic and oncologic outcomes of islet autotransplantation (IAT) in patients undergoing pancreatic surgery for either benign or malignant disease. BACKGROUND: IAT is performed to improve glycemic control after extended pancreatectomy, almost exclusively in patients with chronic pancreatitis. Limited experience is available for other indications or in patients with pancreatic malignancy. METHODS: In addition to chronic pancreatitis, indications for IAT were grade C pancreatic fistula (treated with completion or left pancreatectomy, as indicated); total pancreatectomy as an alternative to high-risk anastomosis during pancreaticoduodenectomy; and distal pancreatectomy for benign/borderline neoplasm of pancreatic body-neck. Malignancy was not an exclusion criterion. Metabolic and oncologic follow-up is presented. RESULTS: From November 2008 to June 2012, 41 patients were candidates to IAT (accounting for 7.5% of all pancreatic resections). Seven of 41 did not receive transplantation for inadequate islet mass (4 pts), patient instability (2 pts), or contamination of islet culture (1 pt). IAT-related complications occurred in 8 pts (23.5%): 4 bleeding, 3 portal thromboses (1 complete, 2 partial), and 1 sepsis. Median follow-up was 546 days. Fifteen of 34 patients (44%) reached insulin independence, 16 patients (47%) had partial graft function, 2 patients (6%) had primary graft nonfunction, and 1 patient (3%) had early graft loss. Seventeen IAT recipients had malignancy (pancreatic or periampullary adenocarcinoma in 14). Two of them had already liver metastases at surgery, 13 were disease-free at last follow-up, and none of 2 patients with tumor recurrence developed metastases in the transplantation site. CONCLUSIONS: Although larger data are needed to definitely exclude the risk of disease dissemination, the present study suggests that IAT indications can be extended to selected patients with neoplasm.

Optimizing utilization of kidneys from deceased donors over 60 years: five-year outcomes after implementation of a combined clinical and histological allocation algorithm.

This 5 year observational multicentre study conducted in the Nord Italian Transplant programme area evaluated outcomes in patients receiving kidneys from donors over 60 years allocated according to a combined clinical and histological algorithm. Low-risk donors 60-69 years without risk factors were allocated to single kidney transplant (LR-SKT) based on clinical criteria. Biopsy was performed in donors over 70 years or 60-69 years with risk factors, allocated to Single (HR-SKT) or Dual kidney transplant (HR-DKT) according to the severity of histological damage. Forty HR-DKTs, 41 HR-SKTs and 234 LR-SKTs were evaluated. Baseline differences generally reflected stratification and allocation criteria. Patient and graft (death censored) survival were 90% and 92% for HR-DKT, 85% and 89% for HR-SKT, 88% and 87% for LR-SKT. The algorithm appeared user-friendly in daily practice and was safe and efficient, as demonstrated by satisfactory outcomes in all groups at 5 years. Clinical criteria performed well in low-risk donors. The excellent outcomes observed in DKTs call for fine-tuning of cut-off scores for allocation to DKT or SKT in high-risk patients.

Multimodal deep learning for COVID-19 prognosis prediction in the emergency department: a bi-centric study.

Predicting clinical deterioration in COVID-19 patients remains a challenging task in the Emergency Department (ED). To address this aim, we developed an artificial neural network using textual (e.g. patient history) and tabular (e.g. laboratory values) data from ED electronic medical reports. The predicted outcomes were 30-day mortality and ICU admission. We included consecutive patients from Humanitas Research Hospital and San Raffaele Hospital in the Milan area between February 20 and May 5, 2020. We included 1296 COVID-19 patients. Textual predictors consisted of patient history, physical exam, and radiological reports. Tabular predictors included age, creatinine, C-reactive protein, hemoglobin, and platelet count. TensorFlow tabular-textual model performance indices were compared to those of models implementing only tabular data. For 30-day mortality, the combined model yielded slightly better performances than the tabular fastai and XGBoost models, with AUC 0.87 ± 0.02, F1 score 0.62 ± 0.10 and an MCC 0.52 ± 0.04 (p < 0.32). As for ICU admission, the combined model MCC was superior (p < 0.024) to the tabular models. Our results suggest that a combined textual and tabular model can effectively predict COVID-19 prognosis which may assist ED physicians in their decision-making process.

Obesity and Lifestyle Habits among Kidney Transplant Recipients.

Background: Obesity may negatively impact clinical outcomes in kidney transplant (KT) recipients. Limited information is available on the prevalence of obesity in this population, and on the lifestyle habits associated with obesity. Methods: we conducted an online, anonymous survey to assess of the proportion of KT recipients with obesity, adherence to the Mediterranean diet (i.e., a dietary regimen with proven renal and cardiovascular outcomes) using the MEDI-Lite questionnaire, and level of physical activity using the International Physical Activity Questionnaire (IPAQ) short form among KT recipients. Results: 255 KT recipients participated. Median (25th−75th quartile) age was 56.0 (48.0; 62.0) years, 43.9% female, median BMI 23.9 (21.6; 26.5) kg/m2. The proportion of KT recipients with obesity was 9.8% (95% confidence interval, 6.4 to 14.1%). Adequate adherence to the Mediterranean diet (Medi-Lite score >9) was overall low (44.7%; 40.0 vs. 45.2% in those with or without obesity, respectively; p = 0.618). In participants with obesity the Medi-Lite score inversely correlated with BMI (R = −0.45; p < 0.025). Overall, 30.6% of participants had a low level of physical activity (44.0 vs. 29.1% of those with or without obesity, respectively; p = 0.125). The amount of energy expended walking was significantly lower among participants with obesity (462 (0.0; 1436) vs. 1056 (433; 2005) METs/week, p = 0.017). Conclusions: the burden of obesity among KT recipients is similar to that of the general population. Adherence to the Mediterranean diet was generally low, and nearly one-third of participants had a low level of physical activity. Building specialized multidisciplinary teams to manage obesity in KT recipients is urgently needed.

Abnormalities of the oculomotor function in type 1 diabetes and diabetic neuropathy.

AIMS: Abnormalities in the oculomotor system may represent an early sign of diabetic neuropathy and are currently poorly studied. We designed an eye-tracking-based test to evaluate oculomotor function in patients with type 1 diabetes. METHODS: We used the SRLab-Tobii TX300 Eye tracker®, an eye-tracking device, coupled with software that we developed to test abnormalities in the oculomotor system. The software consists of a series of eye-tracking tasks divided into 4 classes of parameters (Resistance, Wideness, Pursuit and Velocity) to evaluate both smooth and saccadic movement in different directions. We analyzed the oculomotor system in 34 healthy volunteers and in 34 patients with long-standing type 1 diabetes. RESULTS: Among the 474 parameters analyzed with the eye-tracking-based system, 11% were significantly altered in patients with type 1 diabetes (p < 0.05), with a higher proportion of abnormalities observed in the Wideness (24%) and Resistance (10%) parameters. Patients with type 1 diabetes without diabetic neuropathy showed more frequently anomalous measurements in the Resistance class (p = 0.02). The classes of Velocity and Pursuit were less frequently altered in patients with type 1 diabetes as compared to healthy subjects, with anomalous measurements mainly observed in patients with diabetic neuropathy. CONCLUSIONS: Abnormalities in oculomotor system function can be detected in patients with type 1 diabetes using a novel eye-tracking-based test. A larger cohort study may further determine thresholds of normality and validate whether eye-tracking can be used to non-invasively characterize early signs of diabetic neuropathy. TRIAL: NCT04608890.

Gas-exchange deficit and systemic hypoperfusion in COVID-19 and non-COVID-19 young adult patients with pneumonia.

BACKGROUND: Lung damage leading to gas-exchange deficit and sepsis leading to systemic hypoperfusion are well-known features of severe pneumonia. Although frequently described in COVID-19, their prognostic impact in COVID-19-related pneumonia vs COVID-19-urelated pneumonia has never been compared. This study assesses fundamental gas-exchange and hemodynamic parameters and explores their prognostic impact in COVID-19 pneumonia and non-COVID-19 pneumonia. METHODS: We prospectively evaluated arterial pO2/FiO2, alveolar to arterial O2 gradient, shock index, and serum lactate in 126 COVID-19 pneumonia patients, aged 18- 65, presenting to the emergency department with acute, non-hypercapnic respiratory failure. As a control group we identified 1:1 age-, sex-, and pO2/FiO2-matched COVID-19-urelated pneumonia patients. Univariate and multivariable predictors of 30-day survival were identified in both groups. RESULTS: COVID-19 patients showed lower arterial serum lactate concentration (p<0.001) and shock index (p<0.001) values as compared to non-COVID-19 patients. While we did not observe differences in lactate concentration or in shock index values in deceased vs surviving COVID-19 patients (respectively, p=0.7 and p=0.6), non-COVID-19 deceased patients showed significantly higher lactate and shock index than non-COVID-19 survivors (p<0.001 and p=0.03). The pO2/FiO2 was the most powerful determinant of survival by Cox regression multivariate analysis in COVID-19 patients (p=0.006), while it was lactate in non-COVID-19 patients (p=0.001). CONCLUSIONS: As compared to COVID19-unrelated pneumonia, COVID-19 pneumonia outcome seems more strictly correlated to the extent of lung damage, rather than to the systemic circulatory and metabolic derangements typical of sepsis.