The main characteristics of mechanically ventilated ARDS patients affected with COVID-19, and the adherence to lung-protective ventilation strategies are not well known. We describe characteristics and outcomes of confirmed ARDS in COVID-19 patients managed with invasive mechanical ventilation (MV). Methods: This is a multicenter, prospective, observational study in consecutive, mechanically ventilated patients with ARDS (as defined by the Berlin criteria) affected with with COVID-19 (confirmed SARS-CoV-2 infection in nasal or pharyngeal swab specimens), admitted to a network of 36 Spanish and Andorran intensive care units (ICUs) between March 12 and June 1, 2020. We examined the clinical features, ventilatory management, and clinical outcomes of COVID-19 ARDS patients, and compared some results with other relevant studies in non-COVID-19 ARDS patients. Results: A total of 742 patients were analysed with complete 28-day outcome data: 128 (17.1%) with mild, 331 (44.6%) with moderate, and 283 (38.1%) with severe ARDS. At baseline, defined as the first day on invasive MV, median (IQR) values were: tidal volume 6.9 (6.3-7.8) ml/kg predicted body weight, positive end-expiratory pressure 12 (11-14) cmH 2 O. Values of respiratory system compliance 35 (27-45) ml/cmH 2 O, plateau pressure 25 (22-29) cmH 2 O, and driving pressure 12 (10-16) cmH 2 O were similar to values from non-COVID-19 ARDS patients observed in other studies. Recruitment maneuvers, prone position and neuromuscular blocking agents were used in 79%, 76% and 72% of patients, respectively. The risk of 28-day mortality was lower in mild ARDS [hazard ratio (RR) 0.56 (95% CI 0.33-0.93), p = 0.026] and moderate ARDS [hazard ratio (RR) 0.69 (95% CI 0.47-0.97), p = 0.035] when compared to severe ARDS. The 28-day mortality was similar to other observational studies in non-COVID-19 ARDS patients. Conclusions: In this large series, COVID-19 ARDS patients have features similar to other causes of ARDS, compliance with lung-protective ventilation was high, and the risk of 28-day mortality increased with the degree of ARDS severity.

isrctn.org Identifier: ISRCTN17875607.

No abstract

Aim: To evaluate the utility of intimal thickness and interstitial width as a primary efficacy variable in the design of clinical trials aimed to modify the natural history of chronic allograft nephropathy. Methods: A donor and a 4-month protocol biopsy were evaluated in 40 stable grafts according to the Banff schema. In 27 patients, a second protocol biopsy was done at 1 yr. Arterial intimal volume fraction (Vvintima/ artery) and cortical interstitial volume fraction (Vvinterstitium/cortex) were estimated with a point counting technique. Results: Chronic Banff scores increased during followup, while acute scores reached its peak at 4 months. Vvintima/artery and Vvinterstitium/cortex significantly increased at 4 months, but not at 1 yr. Vvintima/artery at 4 months correlated with donor Vvintima/artery (r Ω0.57, p ∞0.001), histocompatibility (r Ω0.38, p Ω 0.01) and serum cholesterol (r Ω0.31, p Ω0.047). Vvinterstitium/cortex at 4 months correlated with recipient body surface area (r Ω0.44, p Ω0.004) and delayed graft function (p Ω0.016). Power calculations showed that Vvintima/artery and Vvinterstitium/cortex allow an important reduction in minimum sample size of a hypothetical trial aimed to prevent chronic allograft nephropathy. Conclusions: Intimal thickening and interstitial widening progresses rapidly during the first 4 months after transplantation and slowly thereafter. These parameters can be considered as a primary efficacy variable in trials aimed to prevent chronic allograft nephropathy.

Malignancy was confirmed in 20 patients. PET-FDG was positive in all cases. DEP-SPECT was positive in 17 and falselly negative in 3, one carcinoid tumor, one undifferentiated non-small cell adenocarcinoma, and a moderately differentiated adenocarcinoma. In the remaining 9 patients benignancy was confirmed; both studies were normal in 8 and falselly positive in one case of non-specific inflammatory lung process. In 9 out of the 20 cases with malignancy extrapulmonar uptake was seen, with a total number of 19 lesions. In two cases the extrapulmonar uptake were non ganglionar metastasis (bone and adrenal) and in 7 due to mediastinic ganglionar involvement. ROC analysis using peak SUV FDG (cut-off point of 3.5) uptake and target/background depreotide uptake (cut-off point of 1.3) provided, sensitivity and specificity values of 95% and 89% of 84% and 88% for PET and SPECT respectively. It does not exist statistically significant differences between both methods (Z-test SPSS). In summary, FDG-PET has a greater sensitivity and diagnostic accuracy for assessing malignancy of indeterminate lung lesions, and for detection of extrapulmonary involvement, DEP-SPECT represents a good diagnostic alternative for centers where PET is not available.

No abstract

Cancer cells rely on several metabolic pathways such as lipid metabolism to meet the increase in energy demand, cell division, and growth and successfully adapt to challenging environments. Fatty acid synthesis is therefore commonly enhanced in many cancer cell lines. Thus, relevant efforts are being made by the scientific community to inhibit the enzymes involved in lipid metabolism to disrupt cancer cell proliferation. We review the rapidly expanding body of inhibitors that target lipid metabolism, their side effects, and current status in clinical trials as potential therapeutic approaches against cancer. We focus on their molecular, biochemical and structural properties, selectivity and effectiveness and discuss their potential role as antitumor drugs.

Obesity and overweight are associated with lethal diseases. In this context, obese and overweight individuals infected by COVID-19 are at greater risk of dying. Obesity is treated by three main pharmaceutical approaches, namely suppressing appetite, reducing energy intake by impairing absorption, and increasing energy expenditure. Most compounds used for the latter were first envisaged for other medical uses. However, several candidates are now being developed explicitly for targeting obesity by increasing energy expenditure. This review analyzes the compounds that show anti-obesity activity exerted through the energy expenditure pathway. They are classified on the basis of their development status: FDA-approved, Withdrawn, Clinical Trials, and Under Development. The chemical nature, target, mechanisms of action, and description of the current stage of development are described for each one.