Serial Ultrasound Assessment of Diaphragmatic Function and Clinical Outcome in Patients with Amyotrophic Lateral Sclerosis.

Background: Ultrasound (US) evaluation of the diaphragm may be a non-volitional useful tool in the clinical management of patients with ALS. Aim of the present study was then to evaluate the impact of serial assessment of ΔTmax index on clinical outcomes during the follow-up in these patients and to correlate non-volitional US indices and other volitional measures with these outcomes. Methods: A cohort of 39 consecutive patients with ALS was followed up to 24 months. At baseline and every 3-month spirometry (forced vital capacity-FVC), sniff inspiratory nasal pressure (SNIP), and US of the diaphragm (ΔTdi and ΔTmax) were recorded. These parameters were correlated with clinical outcomes (hypercapnia, nocturnal hypoventilation, NIV start in the following 6 month, and death within 1 year). Results: The occurrence of ΔTmax >0.75 during follow-up increased the risk for NIV (HR=5.6, p=0.001) and death (HR=3.7, p=0.0001) compared with patients with stable lower values. The evidence of diaphragmatic dysfunction, i.e. ΔTmax >0.75, occurs 3.2 month earlier than the onset of NIV. Moreover, ΔTmax >0.75 correlated with onset of nocturnal hypoventilation, NIV initiation within 6 months, and death within 12 months, similarly to FVC <50% predicted and better than other functional indices. Conclusions: Serial monitoring of diaphragmatic ΔTmax by US may be useful to predict initiation of NIV and death in patients with ALS. The occurrence of an abnormal ΔTmax value in the follow-up precedes the decision for starting NIV

OTX Genes in Adult Tissues

OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the "toolbox" to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets

One-year persistence of neutralizing anti-SARS-CoV-2 antibodies in dialysis patients recovered from COVID-19

The immunological mechanisms that modulate immune response to SARS-CoV-2 infection remain elusive. Little is known on the magnitude and the durability of antibody response against COVID-19. There is consensus that patients with immune dysfunction, such as dialysis patients, may be unable to mount a robust and durable humoral immunity after infections. Recent studies showed that dialysis patients seroconverted after COVID-19, but data on the durability of the immune response are missing. We reported the data of a durable anti-spike protein seroconversion after natural SARS-CoV-2 infection in three patients on hemodialysis with a mean age of 67.2 +/- 13.8 years. A mean antibody titer of 212.6 +/- 174.9 UA/ml (Liaison (R), DiaSorin) was found after one year (range, 366-374 days) from the diagnosis of COVID-19. In conclusion, this case series provided evidence that patients receiving hemodialysis who recovered from severe COVID-19 were able to mount a long-lasting immune response against SARS-CoV-2. Although the protective capacity of this long-term immunity remains to be determined, these patients did not report signs of reinfection after recovery from COVID-19

Risk of bleeding after percutaneous native kidney biopsy in patients receiving low-dose aspirin: a single-center retrospective study

Background Although discontinuation of antiplatelet agents at least 5 days before kidney biopsy is commonly recommended, the evidence behind this practice is of low level. Indeed, few non-randomized studies previously showed an equivalent risk of bleeding in patients receiving aspirin therapy.Methods We conducted a single center retrospective study comparing the risk of complications after percutaneous native kidney biopsy in patients who received low-dose aspirin (ASA) within 5 days from biopsy and those who did not. The main outcome was the difference in the incidence of major complications (red blood cell transfusion, need for selective arterial embolization, surgery, nephrectomy). Secondary outcomes included difference in minor complications, comparison between patients who received ASA within 48 h or within 3-5 days, identification of independent factors predictive of major complications.Results We analyzed data on 750 patients, of whom 94 received ASA within 5 days from biopsy. There were no significant differences in the proportion of major complications in patients receiving or not receiving ASA (2.59% and 3.19%, respectively, percentage point difference 1%, 95% CI - 3 to 4%, p = 0.74). Groups were also comparable for minor complications; among patients receiving ASA, there were no differences in major bleeding between those who received ASA within 48 h or 3-5 days from biopsy. Significant baseline predictors of major bleeding in our cohort were platelet count lower than 120*10(3)/ microliter, higher diastolic blood pressure and higher blood urea.Conclusions Treatment with low-dose ASA within 5 days from kidney biopsy did not increase the risk of complications after the procedure.[GRAPHICS]

Ultrasound assessed Diaphragm Impairment is a Predictor of Outcomes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease undergoing Non-Invasive Ventilation.

Background. Ultrasound (US) evaluation of diaphragm dysfunction (DD) has proved to be a reliable technique in critical care. In this single center prospective study we investigated the impact of US assessed DD on Non Invasive Ventilation (NIV) failure in AECOPD patients and its correlation with the trans-diaphragmatic pressure assessed through invasive sniff maneuver (Pdi sniff). Methods. A population of 75 consecutive AECOPD with hypercapnic acidosis admitted in our Respiratory Intensive Care Unit (RICU) were enrolled. Change of the diaphragm thickness (\u394Tdi) < 20% during tidal volume was the pre-definite cut off to identify DD+/-. Correlations between \u394Tdi <20% NIV failure and other clinical outcomes was investigated. Correlation between \u394Tdi and Pdi sniff values was analyzed in a subset of 10 patients. Results. DD+ had higher risk for NIV failure as compared with DD- (RR= 4.4, p<0.001) and was significantly associated with greater RICU, in-hospital and 90-day mortality rate, MV duration, tracheostomy rate, and RICU stay. A huge increase in NIV failure (HR=6.2, p< 0.0001) and 90-day mortality (HR=4.7, p=0.008) in DD+ was reported at the Kaplan-Meyer analysis. \u394Tdi highly correlated with Pdi sniff (r Pearson = 0.81, p= 0.004). \u394Tdi< 20% showed better accuracy in predicting NIV failure when compared to baseline pH value and early change of both arterial blood pH and pCO2 following NIV start (AUC=0.84, 0.51, 0.56, 0.54 respectively, p<0.0001). Conclusion. Early and non-invasive US assessment of DD during severe AECOPD is reliable and accurate in identifying patients at major risk for NIV failure and worse prognosis

Soy diet induces intestinal inflammation in adult Zebrafish: Role of OTX and P53 family

Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions of the colon and small intestine, including Crohn's disease and ulcerative colitis. Since Danio rerio is a promising animal model to study gut function, we developed a soy-dependent model of intestinal inflammation in adult zebrafish. The soya bean meal diet was given for 4 weeks and induced an inflammatory process, as demonstrated by morphological changes together with an increased percentage of neutrophils infiltrating the intestinal wall, which developed between the second and fourth week of treatment. Pro-inflammatory genes such as interleukin-1beta, interleukin-8 and tumour necrosis factor alpha were upregulated in the second week and anti-inflammatory genes such as transforming growth factor beta and interleukin-10. Interestingly, an additional expression peak was found for interleukin-8 at the fourth week. Neuronal genes, OTX1 and OTX2, were significantly upregulated in the first two weeks, compatible with the development of the changes in the gut wall. As for the genes of the p53 family such as p53, DNp63 and p73, a statistically significant increase was observed after two weeks of treatment compared with controls. Interestingly, DNp63 and p73 were shown an additional peak after four weeks. Our data demonstrate that soya bean meal diet negatively influences intestinal morphology and immunological function in adult zebrafish showing the features of acute inflammation. Data observed at the fourth week of treatment may suggest initiation of chronic inflammation. Adult zebrafish may represent a promising model to better understand the mechanisms of food-dependent intestinal inflammation