Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study

Background and aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification.Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH.Results: The DLCN score was applied on a sample of 1377 adults (mean age 42.9 +/- 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3-5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score.Conclusions: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). METHODS/DESIGN: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH2O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure 6430 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. DISCUSSION: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration metho

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Pelvic lymph node status prediction in melanoma patients with inguinal lymph node metastasis

none7noThe extent of the groin lymph node (LN) dissection for melanoma is still being debated, particularly in the case of micrometastasis (sentinel lymph node positive). We tested the predictive values of the criteria for pelvic dissection currently suggested by national guidelines (number of positive inguinal LN, Cloquet's LN status, and preoperative computed tomographic scan) and the inguinal lymph node ratio (LNR, the ratio between metastatic and excised LNs) to identify patients with pelvic metastasis. We analyzed the predictive values of the above-mentioned criteria in 157 patients who underwent an ilioinguinal dissection, with a focus on their negative predictive values (NPV), which might help identify low-risk patients who might safely avoid pelvic dissection, pelvic dissection reduction, and error rate. Forty-four (26.7%) patients had pelvic LN metastasis. In patients with micrometastasis (17.3% had pelvic LN metastasis), LNR less than 0.1 and Cloquet's LN status achieved clinically relevant NPV (95.7 and 95.5%, respectively) and pelvic dissection reduction (38.4 and 84.6%, respectively), whereas the error rate was 1.7 and 3.0%, respectively. Lower NPVs were observed for number of positive inguinal LNs (88.6%) and computed tomographic scan (78.4%). Accuracy was enhanced when these criteria were considered in multivariable models. In patients with macrometastasis (36.8% had pelvic LN metastasis), LNR and current selection criteria achieved low NPVs and a high error rate. Avoiding pelvic dissection may be safe in sentinel lymph node-positive patients with LNR less than 0.1. The prediction of pelvic metastasis seems to be less accurate for patients with clinically positive LNs.nonePasquali, Sandro; Mocellin, Simone; Bigolin, Francesco; Vecchiato, Antonella; Montesco, Maria C.; Di Maggio, Antonio; Rossi, Carlo R.Pasquali, Sandro; Mocellin, Simone; Bigolin, Francesco; Vecchiato, Antonella; Montesco, Maria C.; Di Maggio, Antonio; Rossi, CARLO RICCARD

Mappatura Genetica dell' Ipercolesterolemia Familiare: dati preliminari dell'esperienza padovana

Introduzione. L\u2019Ipercolesterolemia Familiare (FH) \ue8 un disordine del metabolismo lipidico su base genetica, rara in omozigosi (1/1000000), ed al contrario interessante 1 soggetto ogni 250 abitanti nella forma eterozigote (HeFH). Il fenotipo lipidico \ue8 caratterizzato da livelli molto elevati di LDL-C dalla nascita, e da un rischio elevato di aterosclerosi coronarica che predispone ad eventi clinici cardiovascolari precoci. Scopo del nostro studio \ue8 stato quello di indagare la potenziale associazione tra genotipo, fenotipo clinico e severit\ue0 del profilo di rischio cardiovascolare, e valutare il potenziale impatto della caratterizzazione genotipica sulla risposta alla terapia farmacologica in pazienti con diagnosi genetica di FH. Materiali e Metodi. Sono stati studiati 69 pazienti con FH, di cui 36 maschi e 33 femmine, con diagnosi clinica e probabile o definita di FH secondo i criteri del Dutch Lipid Clinic Network Score (DLCNS 656). I pazienti sono stati sottoposti ad un prelievo ematico per la ricerca di mutazioni genetiche associate ad FH (geni di LDLR, PCSK9, LDLRAP1 e APO B) come da protocollo dello studio LIPIGEN, ed alla raccolta di parametri clinici e bioumorali, assetto lipidico, parametri di sicurezza epatica e muscolare, metabolismo glucidico, determinati secondo metodi laboratoristici standardizzati. Risultati. Tra i pazienti con HeFH, il 49.2% assumeva una terapia con statine ad elevata efficacia (\ub1 ezetimibe), ma solo il 4.3% dei pazienti raggiungeva livelli target di LDL-C nonostante una riduzione media del LDL-C del 50% (LDL-C alla diagnosi 332.7\ub191.5 mg/dl vs in terapia attuale 167.2\ub153.1 mg/dl). Dei pazienti HeFH affetti da malattia cardiovascolare precoce, il 90% era in terapia ad elevata efficacia, ma nessun paziente raggiungeva il target per LDL-C (LDL-C<70 mg/dl). L\u2019analisi del genotipo ha messo in luce che 55 pazienti (79.7%) presentavano mutazioni nel gene LDLR, 1 paziente nel gene LDLRAP1 in forma omozigote, mentre in 13 pazienti (18.8%) non veniva riscontrata alcuna mutazione nota nei geni testati. Dei pazienti con mutazioni del gene LDLR, 20 (pari al 36.3%) appartenevano alla classe funzionale allele nullo e i restanti 35 pazienti (pari al 63.7%) appartenevano alle altre quattro classi funzionali. Di questi ultimi, 11 presentavano la mutazione FH Padova-1, 2 la mutazione FH Napoli-1, 2 la mutazione FH Napoli-4 e 6 la mutazione FH Palermo-1. Tra i pazienti FH senza mutazione nota, il 70% presentava una diagnosi clinica probabile ed il 30% una diagnosi clinica definita di FH secondo il DLCNS. I pazienti portatori di allele nullo in eterozigosi presentavano un fenotipo clinico pi\uf9 severo rispetto alle altre classi funzionali od ai pazienti privi di mutazioni note. In particolare era evidente un DLCNS pi\uf9 elevato, una presenza significativamente maggiore di xantomi e gerontoxon, livelli di colesterolo totale e LDL-C alla diagnosi significativamente maggiori rispetto agli altri sottogruppi. Per quanto riguarda la risposta alla terapia ipolipemizzante, i pazienti di tutti e tre i sottogruppi sopra considerati presentavano una risposta simile alla terapia farmacologica (LDL-C -50% vs basale), senza differenze statisticamente significative tra i gruppi. Conclusioni. L\u2019ottanta percento dei pazienti con diagnosi clinica di FH formulata mediante DLCNS con cut-off 656 \ue8 risultato portatore di mutazione genetica nota; la caratterizzazione funzionale del genotipo si associa a caratteristiche cliniche fenotipiche diverse, abstract 95 mentre non sembra, nella nostra casistica, predire la risposta alla terapia ipolipemizzante. Viene infine confermata l\u2019assoluta inadeguatezza della terapia ipolipemizzante attuale anche se utilizzata in modo massimale

Anatomical study of the intrahepatic biliary ducts. Parameters that guide the surgical approach in transplanting the left lobe of the liver

Introduction. The techniques of split liver transplantation and transplanting organs from living donors require a thorough anatomical knowledge of biliary drainage, and this is an important factor in preventing complications. Methods. forty-five human livers were used to perform this study. Measurements were made between the confluence of the right hepatic duct (RHD) and the left hepatic duct (LHD) and among the following structures: the venous ligament, the vertex of the confluence of the duct of segment II (DSll) and the duct of segment III (DSIII), the insertion of the duct of the segment I (DSI) and the duct of segment IV (DSIV). Then the distance between the vertex of the confluence of DSII and DSIII and the ligamentum venosum was checked. Results. The LHD had less anatomical variation than the RHD. Four drainage patterns were established for the left lobe, and pattern l, in which the confluence of DSll and DSIII is to the left of the ligamentum venosum, is considered to be the most constant one. A single duct of the confluence of DSll and DSIII was found 1, 2 and 2.5 cm to the right of the ligamentum venosum in 65%, 80%, and 95% of the cases, respectively. Conclusion. It was possible to show evidence of four drainage patterns of the left anatomical lobe of the liver. Furthermore, it was possible to establish the ligamentum venosum as an anatomical reference for locating the confluences of the ducts of the left liver segments

Positive ∂∂ˉ−closed\partial \bar \partial - closed currents and non-Kähler geometrycurrents and non-Kähler geometry

In this paper some new results on positive (de-debar)−closed currents are applied to modifications of compact complex manifolds. The main result in this topic is that every smooth proper modification of a compact Kähler manifold M is balanced. Moreover, under suitable hypotheses on the map, the Kähler degrees of M corresponds to homological properties of the exceptional set of the modification. More examples of p-Kähler manifolds are discussed in the last section of the paper