Remote assessment of the Penn computerised neurocognitive battery in individuals with 22q11.2 deletion syndrome.

BACKGROUND: Neurocognitive functioning is an integral phenotype of 22q11.2 deletion syndrome relating to severity of psychopathology and outcomes. A neurocognitive battery that could be administered remotely to assess multiple cognitive domains would be especially beneficial to research on rare genetic variants, where in-person assessment can be unavailable or burdensome. The current study compares in-person and remote assessments of the Penn computerised neurocognitive battery (CNB). METHODS: Participants (mean age = 17.82, SD = 6.94 years; 48% female) completed the CNB either in-person at a laboratory (n = 222) or remotely (n = 162). RESULTS: Results show that accuracy of CNB performance was equivalent across the two testing locations, while slight differences in speed were detected in 3 of the 11 tasks. CONCLUSIONS: These findings suggest that the CNB can be used in remote settings to assess multiple neurocognitive domains.

Impact of Candida spp. isolation in the respiratory tract in patients with intensive care unit-acquired pneumonia.

In immunocompetent patients with nosocomial pneumonia, the relationship between Candida spp. isolation in respiratory samples and outcomes or association with other pathogens is controversial. We therefore compared the characteristics and outcomes of patients with intensive care unit-acquired pneumonia (ICUAP), with or without Candida spp. isolation in the respiratory tract. In this prospective non-interventional study, we assessed 385 consecutive immunocompetent patients with ICUAP, according to the presence or absence of Candida spp. in lower respiratory tract samples. Candida spp. was isolated in at least one sample in 82 (21%) patients. Patients with Candida spp. had higher severity scores and organ dysfunction at admission and at onset of pneumonia. In multivariate analysis, previous surgery, diabetes mellitus and higher Simplified Acute Physiology Score II at ICU admission independently predicted isolation of Candida spp. There were no significant differences in the rate of specific aetiological pathogens, the systemic inflammatory response, and length of stay between patients with and without Candida spp. Mortality was also similar, even adjusted for potential confounders in propensity-adjusted multivariate analyses (adjusted hazard ratio 1.08, 95% CI 0.57-2.05, p 0.80 for 28-day mortality and adjusted hazard ratio 1.38, 95% CI 0.81-2.35, p 0.24 for 90-day mortality). Antifungal therapy was more frequently prescribed in patients with Candida spp. in respiratory samples but did not influence outcomes. Candida spp. airway isolation in patients with ICUAP is associated with more initial disease severity but does not influence outcomes in these patients, regardless of the use or not of antifungal therapy.

Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study.

BACKGROUND: In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. METHODS: We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. CONCLUSIONS: In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.

Assessment of the bronchodilation test by visual analog scale in the selection of patients with rhinitis for screening spirometry.

BACKGROUND: The nose and bronchi are closely linked, and rhinitis often precedes the onset of asthma. Bronchial obstruction is a characteristic of asthma, and demonstration of its reversibility is a key element in diagnosis. However, reversibility testing requires a spirometer, which is rarely available in the doctor's office. Visual analog scales (VAS) are frequently used in daily practice. OBJECTIVE: This study evaluated the suitability of a VAS for assessing bronchodilation in patients with persistent allergic rhinitis as a means of selecting candidates for screening spirometry. METHODS: We evaluated 120 patients with moderate to severe persistent allergic rhinitis. All patients underwent a clinical examination, skin prick test, spirometry, bronchodilation test, and VAS. RESULTS: Patients with rhinitis showed significantly increased forced expiratory volume in the first second (FEV1) after the bronchodilation test (median, 11.5%). Positive results were observed in 60%, and VAS values increased (>30%) after the test. There was a significant relationship between deltaVAS and deltaFEV1 (P<.0001; r=0.482). CONCLUSION: This preliminary study shows that patients with moderate to severe persistent allergic rhinitis often experience an increase in FEV1 after the bronchodilation test. VAS assessment of the test might be useful when selecting candidates for spirometry for possible bronchial involvement.

Comparison of serum specific IgE and skin prick test in polysensitized patients.

The aim of this study is to evaluate serum specific-IgE in a large group of polysensitized patients with the same SPT result (such as ++++) comparing two diagnostic methods. Six hundred ten patients (310 females; median age 32 years) suffering from allergic rhinitis were studied. Serum specific-IgE were measured by ImmunoCap assay. Skin prick test was also performed. There was a significant difference between serum specific-IgE values in these polysensitized patients. In conclusion, the serum specific-IgE measurement in polysensitized patients seems to be more appropriate than SPT.

Prevalence of metabolic syndrome in long-term survivors of hematopoietic stem cell transplantation.

Our purpose was to determine the prevalence and features of metabolic syndrome (MS) in a series of long-term hematopoietic stem cell transplantation (HSCT) survivors. We assessed the clinical, metabolic and endocrinological data, and plasma TNF, leptin, resistin and adiponectin levels relating to 85 HSCT recipients. MS was diagnosed on the basis of the National Cholesterol Education Program-Adult Treatment Panel III criteria. Its prevalence was compared with that observed in an Italian population, and its relationship with the clinical and laboratory parameters was assessed univariately and multivariately. Twenty-nine HSCT recipients had MS instead of the 12.8 expected (P<0.0001), with hypertriglyceridemia being the most common feature. Univariate analysis indicated that high insulin and leptin levels, low-adiponectin levels and hypogonadism were significantly related to a diagnosis of MS; multivariate analysis indicated plasma leptin, insulin resistance, age and hypogonadism. We conclude that HSCT recipients are at increased risk of a form of MS that has particular clinical features. Plasma leptin levels are independently related to MS, thus suggesting that leptin resistance may play a role as a pathogenetic clue, as in other conditions in which MS occurs as a secondary phenomenon. MS deserves consideration as a life-threatening complication in patients who are probably cured of their underlying disease.

Genes for human general transcription initiation factors TFIIIB, TFIIIB-associated proteins, TFIIIC2 and PTF/SNAPC: functional and positional candidates for tumour predisposition or inherited genetic diseases?

TFIIIB, TFIIIC2, and PTF/SNAPC are heteromultimeric general transcription factors (GTFs) needed for expression of genes encoding small cytoplasmic (scRNAs) and small nuclear RNAs (snRNAs). Their activity is stimulated by viral oncogenes, such as SV40 large T antigen and Adenovirus E1A, and is repressed by specific transcription factors (STFs) acting as anti-oncogenes, such as p53 and pRb. GTFs role as final targets of critical signal transduction pathways, that control cell proliferation and differentiation, and their involvement in gene expression regulation suggest that the genes encoding them are potential proto-oncogenes or anti-oncogenes or may be otherwise involved in the pathogenesis of inherited genetic diseases. To test our hypothesis through the positional candidate gene approach, we have determined the physical localization in the human genome of the 11 genes, encoding the subunits of these GTFs, and of three genes for proteins associated with TFIIIB (GTF3BAPs). Our data, obtained by chromosomal in situ hybridization, radiation hybrids and somatic cell hybrids analysis, demonstrate that these genes are present in the human genome as single copy sequences and that some cluster to the same cytogenetic band, alone or in combination with class II GTFs. Intriguingly, some of them are localized within chromosomal regions where recurrent, cytogenetically detectable mutations are seen in specific neoplasias, such as neuroblastoma, uterine leyomioma, mucoepidermoid carcinoma of the salivary glands and hemangiopericytoma, or where mutations causing inherited genetic diseases map, such as Peutz-Jeghers syndrome. Their molecular function and genomic position make these GTF genes interesting candidates for causal involvement in oncogenesis or in the pathogenesis of inherited genetic diseases.