Respiratory virus detection among healthcare professionals in Brazil: work-related contact and episode recurrence during the COVID-19 pandemic.

OBJECTIVES: Since the beginning of the COVID-19 pandemic, changes in the circulation of respiratory viruses have been observed after measures to control the spread of SARS-CoV-2 were implemented. In this sense, we aimed to understand the circulation of the respiratory virus and its impact in a controlled healthy population of healthcare professional (HCP) volunteers in phase III of the clinical trial of the ChadOx nCoV1 conducted in São Paulo, Brazil. STUDY DESIGN: This was a nested observational cohort study within a clinical trial. METHODS: We performed RT-qPCR to detect SARS-CoV-2, influenza virus A and B (IVA and IVB), respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (hMPV), human coronaviruses (hCoVs: HKU-1, NL63, OC43, and 229-E), parainfluenza virus (PiV) I-IV, and q-PCR for adenovirus in nasopharyngeal and oropharyngeal samples obtained from HCP enrolled in the clinical trial to assess respiratory viruses infection among vaccinated and non-vaccinated. RESULTS: From July 2020 to January 2022, 876 samples were included from 737 volunteers (median age: 33 years, 62.9% female). New episodes were registered for 119 individuals. We observed an overall positivity of 37.7% for SARS-CoV-2 and 16.4% for other respiratory viruses; HRV was the second most detected virus (8%), followed by RSV (2.4%). Fully vaccinated individuals accounted for 53.3% of collected samples, and 52.9% presented at least one respiratory virus infection, with SARS-CoV-2 being the most predominant etiologic agent (62.3%). Influenza and hMPV were not detected among the tested samples. Among the subjects that presented more than one episode, SARS-CoV-2 and HRV infections were related to direct contact with patients (P < 0.002). CONCLUSIONS: Data show high infection rates among HCPs even under mask policies and contact precautions, highlighting the need for improvement in infection control measures in this population regardless of the vaccination program.

Antimicrobial resistance in Aeromonas species isolated from aquatic environments in Brazil.

AIM: The current study was conducted to determine the antimicrobial resistance profile and genetic relatedness of Aeromonas sp. isolated from healthcare and urban effluents, wastewater treatment plant (WWTP) and river water. METHODS AND RESULTS: We detected the presence of genes conferring resistance to ß-lactam, quinolone and aminoglycoside. Multilocus sequence typing was carried out to differentiate the strains, and multilocus phylogenetic analysis was used to identify the species. A total of 28 cefotaxime-resistant Aeromonas sp. strains were identified, harbouring uncommon Guiana-extended-spectrum (GES)-type ß-lactamases (GES-1, GES-5, GES-7 and GES-16). Multidrug-resistant Aeromonas sp. were found in hospital wastewater, WWTP and sanitary effluent, and A. caviae was identified as the most prevalent species (85·7%). CONCLUSION: The release of untreated healthcare effluents, presence of antimicrobials in the environment, in addition to multidrug-resistant Aeromonas sp., are all potential factors for the spread of resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: We identified a vast repertoire of antimicrobial resistance genes (ARG) in Aeromonas sp. from diverse aquatic ecosystems, including those that encode enzymes degrading broad-spectrum antimicrobials widely used to treat healthcare-associated infections. Hospital and sanitary effluents serve as potential sources of bacteria harbouring ARG and are a threat to public health.

Determinants of the effectiveness of fast break actions in elite and sub-elite Italian men's basketball games.

The aim of this study was to examine the determinants of successful and unsuccessful fast-break (FB) actions in elite and sub-elite basketball games. Fifteen 1st-division (elite) and fifteen 3rd-division (sub-elite) Italian men's championship games were analysed across two seasons (2012/2013 and 2013/2014). A binary logistic regression analysis was performed, and the fast-break outcome (successful vs. unsuccessful) was adopted as the dependent variable separately in both elite and sub-elite games. FB execution (initiation, advance and completion phases), typology (primary and secondary break) and the number of players involved (equal number or superiority) were used as independent variables. The results showed that the rate of success of FB actions was 63.5% and 59.7% in elite and sub-elite games, respectively. Moreover, successful FBs were more likely to be completed in the lane in relation to unsuccessful ones in both elite and sub-elite games (p<0.05). Finally, descriptive statistics showed that both elite and sub-elite teams executed FBs similarly. This study highlighted that completion zone was the only predictor of a successful fast break in basketball, while the typology and number of players involved did not predict fast break effectiveness. Moreover, elite and sub-elite teams executed fast break actions similarly. These findings might be useful for basketball coaches to optimize the training of FB actions.

Performance profile of NCAA Division I men's basketball games and training sessions.

This study aimed to analyse live and stoppage time phases, their ratio, and action played on half and full court in college basketball games. Differences were assessed for the entire games and between halves. Moreover, differences of the live/stoppage time ratio were analysed between games and game-based conditioning drills. Ten games as well as fifteen defensive, fourteen offensive and six scrimmage-type drills of the same division I men's college team (13 players) were analysed using time-motion analysis technique. Live and stoppage time were classified in five classes of duration: 1-20, 21-40, 41-60, 61-80, >80 seconds. Half court actions started and finished in the same half court. Full court actions were classified as transfer (TR) phases when at least 3 teammates crossed the mid-court line. TR phases were then classified in 5 classes of frequency: 1TR, 2TR, 3TR, 4TR, and >4TR. The results revealed no statistically significant differences between games or between halves for the considered parameters. The only significant difference was observed for live/stoppage time ratio between halves (p<0.001). Furthermore, a significant difference of the live/stoppage ratio was found between games and game-based drills (p<0.01). Post-hoc analysis demonstrated significant differences of scrimmage-type drills in comparison to games, and defensive and offensive drills (p<0.05), whereas no differences emerged for the other pairwise comparisons. The absence of differences between games in the analysed parameters might be important to characterize the model of performance in division I men's college games. Furthermore, these results encourage coaches to use game-based conditioning drills to replicate the LT/ST ratio documented during games.

Feasibility and reproducibility of spleen transient elastography and its role in combination with liver transient elastography for predicting the severity of chronic viral hepatitis.

Liver transient elastography (L-TE) is a reliable, noninvasive predictor of disease severity in chronic liver disease of viral aetiology (CLD). Owing to the relationships among severity of CLD, portal hypertension and spleen involvement, the assessment of splenic stiffness (S-TE) may have an added value in staging CLD. Of 132 CLD patients of viral aetiology, 48 with myeloproliferative disorders (MD) and 64 healthy volunteers (HV), were concurrently investigated by both L-TE and S-TE. Liver disease severity was staged by liver biopsy (LB; Metavir) taken concurrently with TE examination and upper gastrointestinal tract endoscopy for gastro-oesophageal varices. The S-TE inter-observer agreement was analysed by an intra-class correlation coefficient (ICC); L-TE and S-TE accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. Logistic regression analysis assessed the independent effect of L-TE and S-TE as predictors of hepatic fibrosis stage. S-TE failed in 22 CLD (16.6%), 12 (25%) MD and 12 (18%) HV. In the three groups, the ICC was 0.89 (0.84-0.92), 0.90 (0.85-0.94) and 0.86(0.80-0.91), respectively. In the CLD group, L-TE and S-TE independently predicted significant fibrosis (OR 5.2 and 4.6) and cirrhosis (OR 7.8 and 9.1), but at variance from L-TE, S-TE was independent from liver necroinflammation and steatosis. The NPV of S-TE for gastro-oesophageal varices was 100% using a 48 kPa cut-off. In CLD, spleen stiffness alone or in combination with hepatic stiffness can be reliably and reproducibly assessed by TE with the added value of improving the noninvasive diagnosis of severe liver disease and excluding the presence of oesophageal varices.

Identification of XAF1 as an antagonist of XIAP anti-Caspase activity.

The inhibitors of apoptosis (IAPs) suppress apoptosis through the inhibition of the caspase cascade and thus are key proteins in the control of cell death. Here we have isolated the protein XIAP-associated factor 1 (XAF1) on the basis of its ability to bind XIAP, a member of the IAP family. XIAP suppresses caspase activation and cell death in vitro, and XAF1 antagonizes these XIAP activities. Expression of XAF1 triggers a redistribution of XIAP from the cytosol to the nucleus. XAF1 is ubiquitously expressed in normal tissues, but is present at low or undetectable levels in many different cancer cell lines. Loss of control over apoptotic signalling is now recognized as a critical event in the development of cancer. Our results indicate that XAF1 may be important in mediating the apoptosis resistance of cancer cells.

Role of symptoms, trend of liver tests, and endotherapy in management of post-cholecystectomy biliary leak.

AIM: Biliary leaks are widely reported complications of cholecystectomy, but standard management remains undecided. The objective of our study was to report the role of symptoms, biochemical tests, and ERCP in patients with a leak. MATERIALS AND METHODS: Twenty-one patients (8 M, 26-77 years) with suspected post-cholecystectomy biliary leak were retrospectively studied. Symptoms and liver tests (LTs) after surgery were monitored. Trends of LTs were considered positive if increases at >48 h were seen. ERCP was performed in all patients. Findings at endoscopy and treatments were reported. Outcome results were obtained for all patients. RESULTS: Seventeen of 21 patients had persistent biliary leak at ERCP, because of direct injury (n = 10), accessory duct (n = 4), or cystic duct stump (n = 3). Eleven of 17 patients (six without symptoms), had distal obstruction because of surgical injury (n = 8), stone (n = 2), or cholangiocarcinoma (n = 1) and underwent stenting (n = 4), naso-biliary drainage, NBD (n = 3), or surgery (n = 4). Among the six patients without obstruction (four without symptoms), stenting was performed in two and NBD in four. The four patients without apparent leak underwent NBD. Impairment of LTs was present in ten out of eleven (91%) patients with obstruction versus six of ten (60%) without obstruction. No complications occurred after ERCP. During a median follow-up of 33 months (cholangiocarcinoma excluded) all but one remained asymptomatic. CONCLUSIONS: Symptoms and trend of LTs were not predictive of biliary obstruction in patients with a leak after cholecystectomy. Both endotherapy and surgery had favorable outcomes.

Dynamics simulation of N(2) scattering onto W(100,110) surfaces: A stringent test for the recently developed flexible periodic London-Eyring-Polanyi-Sato potential energy surface.

An efficient method to construct the six dimensional global potential energy surface (PES) for two atoms interacting with a periodic rigid surface, the flexible periodic London-Eyring-Polanyi-Sato model, has been proposed recently. The main advantages of this model, compared to state-of-the-art interpolated ab initio PESs developed in the past, reside in its global nature along with the small number of electronic structure calculations required for its construction. In this work, we investigate to which extent this global representation is able to reproduce the fine details of the scattering dynamics of N(2) onto W(100,110) surfaces reported in previous dynamics simulations based on locally interpolated PESs. The N(2)/W(100) and N(2)/W(110) systems are chosen as benchmarks as they exhibit very unusual and distinct dissociative adsorption dynamics although chemically similar. The reaction pathways as well as the role of dynamic trapping are scrutinized. Besides, elastic/inelastic scattering dynamics including internal state and angular distributions of reflected molecules are also investigated. The results are shown to be in fair agreement with previous theoretical predictions.

[Preventing and reducing comorbidity in candidates for kidney transplantation for the improvement of post-operative results]. / Prevenire e ridurre le comorbilita' nei candidati al trapianto di rene per migliorare i risultati post-trapianto.

The correct and constant management of transplant waiting lists is necessary for the optimal utilization of the limited number of organs available for transplantation. The guidelines regarding placement on transplant waiting lists (absolute and relative contraindications) are well documented, even though they are in constant development. The criteria for the monitoring of patients on waiting lists, however, are not so well defined; this aspect is subject to careful evaluation on account of the widening of the criteria for transplantation suitability, the increase in the average age of patients, a rise in the number of enrolments and, as a result, prolonged waiting time (in Italy, the average time spent on a waiting list is 37 months). During the waiting period, a greater risk of clinically significant comorbidities and mortality, above all from cardiovascular events, has been noted (the annual mortality is 5-7% in the US, 1.3% in Italy). An in-depth clinical and instrumental study of patients with chronic renal failure is necessary when screening eligible candidates for transplant programs, individualizing therapeutic strategies, and identifying patients for whom the risks outweigh the potential benefits. Clinical and instrumental monitoring, as well as adequate treatment of comorbidities during the waiting period, can help improve the post-transplant outcome. This work examines the study algorithms and monitoring procedures for patients on kidney transplant waiting lists.

Physical and physiological demands and hormonal responses in basketball small-sided games with different tactical tasks and training regimes.

OBJECTIVES: To evaluate external and internal training load (TL) and hormonal responses in basketball 3-versus-3 small-sided games (SSGs). DESIGN: Randomized repeated-measures study. METHODS: Twelve male basketball players participated to four 3-versus-3 SSGs characterized by different tactical tasks (offensive; defensive) and training regimes (long-intermittent: three 4-min bouts with 2' rest in between; short-intermittent: six 2-min bouts with 1' rest in between). Variables measured were: PlayerLoad (PL); percentage of maximal heart rate (%HRmax); Edwards' TL. Before and after the SSGs, saliva samples were collected to measure cortisol (C) and testosterone (T). Two-way (task; regime) repeated-measures ANOVA was performed for PL and %HRmax; C concentrations were analysed with a three-way (task; regime; time: pre/post) repeated-measures ANOVA; non-parametric analyses were performed for Edwards' TL and T. RESULTS: PL was moderately higher in offensive task (148.0±16.8 AU) compared to defensive (137.1±15.5 AU), and short regime (147.0±18.2 AU) compared to long (137.9±14.6 AU). %HRmax was moderately higher in offensive task (91.1±4.1%) compared to defensive: (88.7±5.4%), while it did not differ between regimes (long: 90.0±5.6%) (short: 89.8±4.2%); additionally, an interaction (task*regime) effect was found (ES: strong). Edwards' TL was moderately higher in offense-long SSG (56.6+2.4 AU) compared to defense-short (52.4+4.4 AU). C increased after the SSGs (ES: strong). T decreased after offense-short (ES: moderate) and increased after defense-long (ES: moderate) SSGs. CONCLUSIONS: Tactical tasks and training regimes influence external and internal demands of basketball SSGs. Steroid hormones respond in SSGs.

Mapping ligand binding pockets in chloride ClC-1 channels through an integrated in silico and experimental approach using anthracene-9-carboxylic acid and niflumic acid.

BACKGROUND AND PURPOSE: Although chloride channels are involved in several physiological processes and acquired diseases, the availability of compounds selectively targeting CLC proteins is limited. ClC-1 channels are responsible for sarcolemma repolarization after an action potential in skeletal muscle and have been associated with myotonia congenita and myotonic dystrophy as well as with other muscular physiopathological conditions. To date only a few ClC-1 blockers have been discovered, such as anthracene-9-carboxylic acid (9-AC) and niflumic acid (NFA), whereas no activator exists. The absence of a ClC-1 structure and the limited information regarding the binding pockets in CLC channels hamper the identification of improved modulators. EXPERIMENTAL APPROACH: Here we provide an in-depth characterization of drug binding pockets in ClC-1 through an integrated in silico and experimental approach. We first searched putative cavities in a homology model of ClC-1 built upon an eukaryotic CLC crystal structure, and then validated in silico data by measuring the blocking ability of 9-AC and NFA on mutant ClC-1 channels expressed in HEK 293 cells. KEY RESULTS: We identified four putative binding cavities in ClC-1. 9-AC appears to interact with residues K231, R421 and F484 within the channel pore. We also identified one preferential binding cavity for NFA and propose R421 and F484 as critical residues. CONCLUSIONS AND IMPLICATIONS: This study represents the first effort to delineate the binding sites of ClC-1. This information is fundamental to discover compounds useful in the treatment of ClC-1-associated dysfunctions and might represent a starting point for specifically targeting other CLC proteins.

The Sgs1 helicase of Saccharomyces cerevisiae inhibits retrotransposition of Ty1 multimeric arrays.

Ty1 retrotransposons in the yeast Saccharomyces cerevisiae are maintained in a genetically competent but transpositionally dormant state. When located in the ribosomal DNA (rDNA) locus, Ty1 elements are transcriptionally silenced by the specialized heterochromatin that inhibits rDNA repeat recombination. In addition, transposition of all Ty1 elements is repressed at multiple posttranscriptional levels. Here, we demonstrate that Sgs1, a RecQ helicase required for genome stability, inhibits the mobility of Ty1 elements by a posttranslational mechanism. Using an assay for the mobility of Ty1 cDNA via integration or homologous recombination, we found that the mobility of both euchromatic and rDNA-Ty1 elements was increased 32- to 79-fold in sgs1Delta mutants. Increased Ty1 mobility was not due to derepression of silent rDNA-Ty1 elements, since deletion of SGS1 reduced the mitotic stability of rDNA-Ty1 elements but did not stimulate their transcription. Furthermore, deletion of SGS1 did not significantly increase the levels of total Ty1 RNA, protein, or cDNA and did not alter the level or specificity of Ty1 integration. Instead, Ty1 cDNA molecules recombined at a high frequency in sgs1Delta mutants, resulting in transposition of heterogeneous Ty1 multimers. Formation of Ty1 multimers required the homologous recombination protein Rad52 but did not involve recombination between Ty1 cDNA and genomic Ty1 elements. Therefore, Ty1 multimers that transpose at a high frequency in sgs1Delta mutants are formed by intermolecular recombination between extrachromosomal Ty1 cDNA molecules before or during integration. Our data provide the first evidence that the host cell promotes retrotransposition of monomeric Ty1 elements by repressing cDNA recombination.

Posttranslational regulation of Ty1 retrotransposition by mitogen-activated protein kinase Fus3.

Ty1 retrotransposons in Saccharomyces cerevisiae are maintained in a state of transpositional dormancy. We isolated a mutation, rtt100-1, that increases the transposition of genomic Ty1 elements 18- to 56-fold but has little effect on the transposition of related Ty2 elements. rtt100-1 was shown to be a null allele of the FUS3 gene, which encodes a haploid-specific mitogen-activated protein kinase. In fus3 mutants, the levels of Ty1 RNA, protein synthesis, and proteolytic processing were not altered relative to those in FUS3 strains but steady-state levels of TyA, integrase, and reverse transcriptase proteins and Ty1 cDNA were all increased. These findings suggest that Fus3 suppresses Ty1 transposition by destabilizing viruslike particle-associated proteins. The Fus3 kinase is activated through the mating-pheromone response pathway by phosphorylation at basal levels in naive cells and at enhanced levels in pheromone-treated cells. We demonstrate that suppression of Ty1 transposition in naive cells requires basal levels of Fus3 activation. Substitution of conserved amino acids required for activation of Fus3 derepressed Ty1 transposition. Moreover, epistasis analyses revealed that components of the pheromone response pathway that act upstream of Fus3, including Ste4, Ste5, Ste7, and Ste11, are required for the posttranslational suppression of Ty1 transposition by Fus3. The regulation of Ty1 transposition by Fus3 provides a haploid-specific mechanism through which environmental signals can modulate the levels of retrotransposition.

Wireless pH monitoring: better tolerability and lower impact on daily habits.

BACKGROUND: Twenty-four hours oesophageal pH monitoring is considered the reference-standard for the diagnosis of gastro-oesophageal reflux disease, but it is limited by catheter discomfort and limitations of daily habits. AIM: We evaluated tolerability and impact on food intake and daily activities of catheter-based compared to wireless pH monitoring. PATIENTS: One-hundred and thirty-three consecutive patients with suspected gastro-oesophageal reflux disease were enrolled. METHODS: Seventy-eight patients (36 M, 53+/-2 years) underwent the 24 h catheter-based and 55 patients (25 M, 44+/-3 years) the 48 h wireless pH monitoring. Discomfort at placement and during the test was evaluated by 100 mm visual analogue scales. Limitations of food intake and of daily activities were evaluated by standardized questionnaires (score 0 to 3). RESULTS: Discomfort (mean+/-standard error of the mean) at placement and during the test was 32+/-3 versus 29+/-4 (p=ns) and 37+/-3 versus 22+/-3 (p<0.001) for the catheter-based versus wireless techniques. Limitation of food intake and of daily activities (mean+/-standard error of the mean) were 0.9+/-0.1 versus 0.4+/-0.1 (p<0.05) and 1.2+/-0.1 versus 0.2+/-0.1 (p<0.0001), respectively. CONCLUSIONS: The wireless pH monitoring is better tolerated and has minor impact on daily habits compared to the traditional technique. Whether this translates into better diagnostic accuracy remains to be evaluated.

Elective surgery for benign liver tumours.

BACKGROUND: Benign liver tumours (haemangioma, focal nodular hyperplasia, and hepatic adenoma) have different prevalence and prognosis. Spontaneous rupture and malignant transformation can complicate hepatic adenoma. Elective surgery is controversial, and indications are represented by uncertain diagnosis, presence of symptoms, and prevention of major complications. OBJECTIVES: To assess the beneficial and harmful effects of elective surgery of benign liver tumours. We identified 31 cases series. These were small (with less than 60 participants) and the types of tumours mixed. These studies reported no significant mortality, but in the six studies with mortality it ranged from 1% to 17%. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (searches in Issue 1, 2006), MEDLINE, EMBASE, CancerLit, and Science Citation Index Expanded (SCI-EXPANDED) (searched December 2005). A further search included the proceedings of major hepatological and surgical congresses (Annual Meetings of the American Association for the Study of the Liver (AASLD) and European Association for the Study of the Liver (EASL)), and examination of the references of relevant papers and reference lists of the identified studies. SELECTION CRITERIA: Randomised clinical trials in adult patients with benign liver tumours without indications for emergency surgery in which elective surgery (resection) versus no intervention or sham operation are compared. DATA COLLECTION AND ANALYSIS: All trials identified through searches were evaluated for eligibility for inclusion. We intended to extract relevant data in order to analyse the outcomes as per our published protocol using intention-to-treat analysis. MAIN RESULTS: We could not identify any randomised clinical trials. AUTHORS' CONCLUSIONS: We were unable to find evidence supporting or refuting elective surgery for patients with benign liver tumours. We need large, long-term randomised clinical trials with adequate methodology to assess the benefits and harms of elective surgery.

Evaluation of IGF-I levels during long-term somatostatin analogs treatment in patients with gastroenteropancreatic endocrine tumors.

Previous experiments reported desensitization to SS action in rat anterior pituitary cells and cell lines. The aim of the study was to verify whether the lack of desensitization to SS analogs (SSa) observed in acromegalic patients was also present in subjects with normal hypothalamic-pituitary function. The effect of chronic treatment with octreotide long-acting release (o-LAR, 10-30 mg/28 days) on IGF-I levels was then evaluated in 23 patients with gastroenteropancreatic (GEP) endocrine tumors (8 gastrinomas, 6 carcinoids, and 9 functioning pancreatic tumors). Serum IGF-I, clinical symptoms, plasma chromogranin-A (CgA) and markers of hepatic synthesis were evaluated before and after a short-term period in all the patients (median 4.5 months), after a medium-term period in 12 (median 18 months) and after a long-term follow-up period in 9 of them (median 48 months). Mean IGF-I levels decreased from 17.3+/-7.0 to 12.8+/-6.2 nmol/l in the short-term (p<0.005) being reduced from baseline concentrations in 87% and under the normal range for age in 35% of patients. Afterwards, they always remained stable both in the medium- and long-term periods, still being low in 3/12 and 2/9 patients, respectively. No alterations in biochemical markers of liver function were found either before or during therapy. No correlation between IGF-I levels, CgA concentrations and/or clinical definitive outcome was observed. In conclusion, the study demonstrated that: a) similarly to that observed in acromegalic patients, chronic o-LAR treatment did not induce desensitization of pituitary SS receptors (SSR) in humans with intact hypothalamic-pituitary axis, and b) in patients with GEP endocrine tumors, GH/IGF-I inhibition did not contribute to SSa efficacy.

Combined liver-kidney transplantation--S. Orsola experience: nephrological aspects.

Combined liver kidney transplantation (LKT) has the potential to provide a complete recovery of liver and kidney failure; the literature reports an increase in LKT in the last few years and an improvement in patient and graft survival. In our experience 15 patients underwent LKT from 1997 to 2005. The mean age was 50 +/- 9 years (range 34 to 63). The patients were affected by viral (n = 9), alcoholic (n = 1), polycystic (n = 2), cholangitis (n = 1), cholestatic (n = 1), or amyloidotic (n = 1) chronic hepatopathy. Chronic renal failure (CRF) was due to polycystic kidney disease (n = 4), IgA (n = 2), interstitial nephropathy (n = 2), glomerulonephritis (n = 4), amyloidosis (n = 1), vascular nephropathy (n = 1), of unknown end-stage renal disease (n = 1). Twelve of 15 patients were on renal dialysis treatment, three patients had moderate/severe CRF. Two patients had previously been transplanted (kidney). All patients were selected based upon blood group identity and negative cross-match before kidney transplant. Histocompatibility matching (HLA) was not included in the selection criteria. We did not observe delayed graft function. After a mean follow-up was 23 +/- 32 months (range 5 to 99), 12 subjects show, normal hepatic and renal function. At the beginning of our experience two patients in bad clinical condition died within 3 months because of sepsis, and one died because of a malignancy after 7 years. Both organs were functioning well in the deceased patients. Survival analysis confirms LKT efficacy: at 5 years follow-up patient survival is 86%, graft survival censored for death 100%. Only two subjects had an acute rejection episode in the first year; the kidney rejection incidence was lower than that reported for an isolated kidney transplant (13% vs 21%).

Nephrological indications in combined liver-kidney transplantation.

In isolated liver transplantation pretransplant renal failure is a major mortality risk, there are no guidelines at the moment to establish the indications for a combined liver-kidney transplantation (LKT). In irreversible chronic renal failure (CRF) not on dialysis, nephrological evaluation is required to assess the need for a simultaneous kidney transplantation. There are no experiences about the functional contribution of native kidneys post-LKT. Herein we have reported the case of two patients who underwent LKT in 2004 due to CRF, not yet on dialysis. At the moment of LKT, the first patient (polycystic kidney disease) had a glomerular filtration rate (GFR) = 29 mL/min, and the second recipient (vascular nephropathy and diabetes), a GFR = 33 mL/min. In both cases we did not observe delayed graft function. At discharge the serum creatinine was 1.1 and 1.0 mg/dL, respectively, which was maintained during follow-up. In both cases renal scintigraphy with Tc-99 DMSA was performed to evaluate the functional contributions of transplanted versus native kidneys. In the first case scintigraphy at 9 months after LKT demonstrated an 81% contribution from the transplanted kidney, 9% from the right and 10% from the left native kidneys. In the second case, at 3 months after LKT, the functional contributions were 76%, 10%, and 14%, respectively. The transplanted kidney nephron mass may avoid the need for hemodialysis in the early posttransplant period; in the midterm it may help to maintain residual renal function. As in other combined transplant programs (heart-kidney, kidney-pancreas) with irreversible CRF, a GFR < or = 30 to 35 mL/min may be an indication for LKT, but we need more experience.

Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients.

We evaluated whether the amount of circulating DNA in plasma could discriminate between lung cancer patients and healthy individuals and whether it is related to disease progression, and we analyzed the kinetics of plasma DNA in disease-free, surgically resected patients. Plasma DNA quantification and analysis of microsatellite alterations were performed in a consecutive series of 84 patients with non-small cell lung cancer, who were studied during follow-up, and 43 healthy controls. In patients, the mean values of plasma DNA concentration were higher than in controls even considering stage Ia patients. Sensitivity and specificity estimates were calculated as the area under the receiver operating characteristic curve (AUC-ROC) curve and showed a value of 0.844. Variations in DNA level and in microsatellite changes correlated with the clinical status of 38 patients monitored during follow-up. The data suggest that quantification and molecular characterization of plasma DNA in lung cancer patients are valuable noninvasive diagnostic tools for discriminating patients from unaffected individuals and for detecting early recurrence during follow-up.

Liver stiffness measurement reliability and main determinants of point shear-wave elastography in patients with chronic liver disease.

BACKGROUND: Liver stiffness (LS) measured by transient elastography (TE) accurately predicts the severity of chronic liver diseases (CLD). Point quantification shear-wave elastography (pSWE) is a new technique incorporated into a conventional ultrasound system for measuring LS. We evaluated pSWE feasibility, reproducibility and diagnostic accuracy in consecutively recruited CLD patients who concomitantly underwent TE and liver biopsy. AIM: To evaluate pSWE feasibility, reproducibility and diagnostic accuracy in consecutively recruited CLD patients who concomitantly underwent TE and liver biopsy. METHODS: Over 2 years 186 CLD patients (116 males, 132 viral hepatitis) consecutively underwent pSWE (10 valid measurements by ElastPQ) blindly performed by two raters. A further operator performed TE. Inter-observer agreement for pSWE was analysed by intraclass correlation coefficient (ICC) and correlated with histological liver fibrosis (METAVIR). Main determinants of pSWE were investigated by linear regression model. RESULTS: Three hundred and seventy-two (100%) reliable measurements were obtained by pSWE and 184 by TE (99%). LS was 8.1 ± 4.5 kPa for pSWE with the first rater and 8.0 ± 4.2 kPa with the second one vs. 8.8 ± 3.6 kPa for TE. pSWE ICC was 0.89 (95% CI 0.85-0.91), not influenced by age, sex, BMI, liver enzymes, liver aetiology. ICC increased over time with year 1 at 0.86 and 95% CI 0.81-0.90 vs. year 2 at 0.92 and 95% CI 0.87-0.95. Liver fibrosis was the only independent determinant of LS on pSWE. The AUROCs for diagnosing F ≥ 2, F ≥ 3 and F = 4 were 0.77, 0.85 and 0.88 for pSWE vs. 0.81, 0.88 and 0.94 for TE. After 1-year training they were 0.86, 0.94 and 0.91. CONCLUSION: Point quantification shear-wave elastography reliably and reproducibly evaluates liver stiffness, matching transient elastography for accuracy after a 1-year learning curve or 130 examinations.