NT pro BNP plasma level and atrial volume are linked to the severity of liver cirrhosis.

BACKGROUND AND AIMS: Plasma levels of NT-pro-BNP, a natriuretic peptide precursor, are raised in the presence of fluid retention of cardiac origin and can be used as markers of cardiac dysfunction. Recent studies showed high levels of NT pro BNP in patients with cirrhosis. We assessed NT pro-BNP and other parameters of cardiac dysfunction in patients with cirrhosis, with or without ascites, in order to determine whether the behaviour of NT pro BNP is linked to the stage of liver disease or to secondary cardiac dysfunction. METHODS: Fifty eight consecutive hospitalized patients mostly with viral or NAFLD-related cirrhosis were studied. All underwent abdominal ultrasound and upper GI endoscopy. Cardiac morpho-functional changes were evaluated by echocardiography and NT-pro-BNP plasma levels determined upon admission. Twenty-eight hypertensive patients, without evidence of liver disease served as controls. RESULTS: Fifty eight cirrhotic patients (72% men) with a median age of 62 years (11% with mild arterial hypertension and 31% with type 2 diabetes) had a normal renal function (mean creatinine 0.9 mg/dl, range 0.7-1.06). As compared to controls, cirrhotic patients had higher NT pro-BNP plasma levels (365.2±365.2 vs 70.8±70.6 pg/ml; p<0.001). Left atrial volume (LAV) (61.8±26.3 vs 43.5±14.1 ml; p = 0.001), and left ventricular ejection fraction (62.7±6.9 vs. 65.5±4%,; p = 0.05) were also altered in cirrhotic patients that in controls. Patients with F2-F3 oesophageal varices as compared to F0/F1, showed higher e' velocity (0.91±0.23 vs 0.66±0.19 m/s, p<0.001), and accordingly a higher E/A ratio (1.21±0.46 vs 0.89±0.33 m/s., p = 0.006). CONCLUSION: NT-pro-BNP plasma levels are increased proportionally to the stage of chronic liver disease. Advanced cirrhosis and high NT-pro-BNP levels are significantly associated to increased LAV and to signs of cardiac diastolic dysfunction. NT pro-BNP levels could hence be an useful prognostic indicators of early decompensation of cirrhosis

preoperative therapy with trastuzumab and oral vinorelbine endocrine therapy in patients with her2 positive breast cancer

Abstract Background Combined trastuzumab and intravenous vinorelbine yielded high clinical activity as preoperative treatment in patients (pts) with HER 2/ neu positive breast cancer. Patients and methods We tested a preoperative combination of trastuzumab with oral vinorelbine (oV) in pts with locally advanced (T2-T4 N0-3 M0) HER2-positive breast cancer. Trastuzumab was administered i.v q 3 wks and oV was administered at the dose of 55 mg/sqm on days 1 and 3 q 3 wks, for 8 courses. Pts with ER ≥ 10% tumors received endocrine therapy with letrozole 2.5 mg/day, plus monthly triptorelin if premenopausal. Results Forty-five pts entered the study. The overall response rate (CR + PR) was 76% (95% CI: 60%–87%). pCR was observed in 4 pts (10%). Among ER-positive tumors 21/25 pts obtained a clinical response (84%) and two pts obtained a pCR (8%). Conclusions The combination of trastuzumab and oral vinorelbine demonstrated encouraging activity in patients with HER 2 positive ER-positive tumors. Alternative strategies should be investigated in patients with endocrine non responsive disease

Immunohistochemical analysis of axillary skin biopsies for the detection of adrenergic innervation of sweat glands in normal subjects and Parkinson’s disease patients

Beside the typical motor symptoms Parkinson’s disease (PD) is characterized, with varying severity, by autonomic dysfunction. Several studies have shed light on the anatomical and molecular changes that underlie the peripheral neuronal degeneration associated with PD and other Lewy body (LB) diseases (LBDs). By using skin biopsies from LBDs patients it was possible to detect misfolded phospho-α-synuclein (p-syn) deposits within dermal nerve fibers and correlate them with a reduced density of small nerve fibers. (1, 2). The skin biopsy approach is an inexpensive and minimally invasive technique. To date, there is not a standardized procedure for sampling site, tissue processing and nerve fibre assessment, so the goal of a diagnostic instrument for an early diagnosis of (LBDs) still remains a challenge. We have carried out a retrospective study setting up a novel protocol based on 10 µm thick serial sections from FFPE axillary skin biopsies. This choice take advantage from the presence of apocrine glands in the axillary region, as they receive a dense sympathetic adrenergic innervation, exploitable for a clear nervous fibers tracking. The biopsies were taken from 14 individuals who had been, in the first instance, diagnosed with various traits of motor and neurological dysfunction and two control subjects. Serial tissue sections were analysed by IHC (DAB chromogen) and by immunofluorescent labelling, using anti-p-α-synuclein (S129), anti- α -synuclein, anti-PGP9.5 and anti-tyrosine hydroxylase antibodies. This particular setting has proven useful to well highlight the adrenergic fibers surrounding the apocrine sweat glands and to visualize the fibers α -synuclein deposition. Our results enabled us to support the first diagnosis in various cases with probable PD but gave a negative p-Syn-S129 immunoreactivity results for samples from vascular Parkinson, multiple system atrophy, essential tremor and frontotemporal dementia. Our methodological setting is able to detect the adrenergic innervation of sweat apocrine glands and both the presence of Lewy bodies and Lewy neurites in axillary skin biopsies

topoisomerase iiα gene status and prediction of pathological complete remission after anthracycline based neoadjuvant chemotherapy in endocrine non responsive her2 neu positive breast cancer

Abstract Purpose Topoisomerase IIα (Topo II) is a potential marker of responsiveness to anthracycline-based therapy. We analyzed the role of Topo II gene status in the prediction of pathological complete remission (pCR) after primary anthracycline-based chemotherapy in non- endocrine responsive breast cancers overexpressing Her2/neu. Methods Twenty-three patients, with T2–T4, ER and PgR absent, overexpressing Her2/neu breast cancers treated with anthracycline-based chemotherapy were evaluated. Topo II gene status was assessed by FISH in pre-treatment tumor specimens and the results were correlated to pathological and clinical responses. Results Overall, six patients had a pCR (26%). Topo II was amplified in 5 (22%) of the tumors. In all patients with Topo II amplification, Her2/neu gene amplification was also detected. Among patients without amplification, one had polysomia of chromosome (Cr) 17 and four patients had deletion of the Topo II gene. A higher probability of pCR was observed when Topo II amplification and Cr 17 polysomy were present: pCR was reported in 3 of 5 amplified tumors (60%), in the polysomic tumor (amplified plus polysomic 67%) and in only 2 out of 13 tumors without alteration of Topo II status (15%). If we compare the frequency of pCR in tumors with amplification or polysomy versus the frequency of tumors with not amplification (deletion or no modification), a significant difference was detected ( p =0.02). One progressive disease (PD) was reported in one tumor with Topo II deletion (1/4, 25%) and one in tumor without any modification of Topo II gene status (1/13, 8%). Conclusions In patients with endocrine unresponsive and Her2 overexpressing tumors, Topo II amplification or the presence of chromosome 17 polysomy correlate with a significantly high probability of achieving pCR after neoadjuvant, anthracycline-based chemotherapy. Further prospective studies in order to more clearly define the predictive role of Topo II status in this subgroup of patients are warranted

Post-intubation tracheal lacerations: Risk-stratification and treatment protocol according to morphological classification

BackgroundPost-intubation tracheal laceration (PITL) is a rare condition (0.005% of intubations). The treatment of choice has traditionally been surgical repair. Following our first report in 2010 of treatment protocol tailored to a risk-stratified morphological classification there is now clear evidence that conservative therapy represents the gold standard in the majority of patients. In this paper we aim to validate our risk-stratified treatment protocol through the largest ever reported series of patients. MethodsThis retrospective analysis is based on a prospectively collected series (2003-2020) of 62 patients with PITL, staged and treated according to our revised morphological classification. ResultsFifty-five patients with Level I (#8), II (#36) and IIIA (#11) PITL were successfully treated conservatively. Six patients with Level IIIB injury and 1 patient with Level IV underwent a surgical repair of the trachea. No mortality was reported. Bronchoscopy confirmed complete healing in all patients by day 30. Statistical analysis showed age only to be a risk factor for PITL severity. ConclusionsOur previously proposed risk-stratified morphological classification has been validated as the major tool for defining the type of treatment in PITL

Mycobacterium tuberculosis SIT42 Infection in an Abused Dog in Southern Italy

A case of Mycobacterium tuberculosis infection is described in a dead adult male dog in Southern Italy. The carcass was found by the Health Authority in a gypsy encampment. It was admitted to our forensic veterinary medicine unit, with a suspicion of cruelty to the animal. Necropsy showed beating and traumatism signs, and mistreating was confirmed. Gross lesions included multiple nodular hepatic lesions, hemorrhagic enteritis with enlarged mesenteric lymph nodes, body cavity effusions, and an adrenal neoplasm. Bacteriological and molecular analyses were carried out on the liver lesions that enabled to identify M. tuberculosis SIT42 (LAM9). Drug-resistance patterns were evaluated by screening mutations on the rpoB and katG genes that showed susceptibility to both rifampin and isoniazid, respectively. Very few studies report canine tuberculosis, and little is known about the disease in Italy. To the authors' knowledge, this is the first report of Mycobacterium tuberculosis SIT42 infection in a dog in Italy

Gruppo INDACO: Report della divulgazione per i progetti ASTRI e CTA Anni 2021-2022

Il gruppo INDACO (INAF per la Divulgazione di ASTRI e CTA Observatory) si è costituito alla fine del 2020 per occuparsi della divulgazione dei due progetti, ASTRI e CTA Observatory, per conto di INAF. Dopo i primi due anni di lavoro, facciamo il punto di quanto affrontato e raggiunto finora e delle prospettive future

Microenvironmental regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence

Although the progression of chronic lymphocytic leukemia (CLL) requires the cooperation of the microenvironment, the exact cellular and molecular mechanisms involved are still unclear. We investigated the interleukin (IL)-23 receptor (IL-23R)/IL-23 axis and found that circulating cells from early-stage CLL patients with shorter time-to-treatment, but not of those with a more benign course, expressed a defective form of the IL-23R complex lacking the IL-12R beta 1 chain. However, cells from both patient groups expressed the complete IL-23R complex in tissue infiltrates and could be induced to express the IL-12R. 1 chain when cocultured with activated T cells or CD40L(+) cells. CLL cells activated in vitro in this context produced IL-23, a finding that, together with the presence of IL-23 in CLL lymphoid tissues, suggests the existence of an autocrine/paracrine loop inducing CLL cell proliferation. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 antibody proved effective in controlling disease onset and expansion in xenografted mice, suggesting potential therapeutic strategies

Ancient marine sediment DNA reveals diatom transition in Antarctica

Antarctica is one of the most vulnerable regions to climate change on Earth and studying the past and present responses of this polar marine ecosystem to environmental change is a matter of urgency. Sedimentary ancient DNA (sedaDNA) analysis can provide such insights into past ecosystem-wide changes. Here we present authenticated (through extensive contamination control and sedaDNA damage analysis) metagenomic marine eukaryote sedaDNA from the Scotia Sea region acquired during IODP Expedition 382. We also provide a marine eukaryote sedaDNA record of ~1 Mio. years and diatom and chlorophyte sedaDNA dating back to ~540 ka (using taxonomic marker genes SSU, LSU, psbO). We find evidence of warm phases being associated with high relative diatom abundance, and a marked transition from diatoms comprising <10% of all eukaryotes prior to ~14.5 ka, to ~50% after this time, i.e., following Meltwater Pulse 1A, alongside a composition change from sea-ice to open-ocean species. Our study demonstrates that sedaDNA tools can be expanded to hundreds of thousands of years, opening the pathway to the study of ecosystem-wide marine shifts and paleo-productivity phases throughout multiple glacial-interglacial cycles