Donor-Model for End-Stage Liver Disease and donor-recipient matching in liver transplantation

Background

The product between donor (D) age and recipient (R) Model for End-Stage Liver Disease (MELD) score at the moment of liver transplantation (LT) has been proposed as a potential D-R matching tool to reduce the risk of “futile” LT from using the MELD score as the main allocation tool. The aim of this study was to evaluate the prognostic ability of D-MELD among a cohort of Italian patients already selected for LT on the basis of a D-R matching philosophy.

Methods

We studied 303 consecutive adult patients undergoing first LT for chronic liver diseases with available D-MELD at the moment of LT from 2003 to 2009. Optimal donors were assigned to more severe cirrhotic patients (MELD ≥20); suboptimal organs were allocated to patients with hepatocellular carcinoma (HCC) not responsive to bridging therapies (specific priority score) or other exceptions with MELD <20. A suboptimal donor had age >70 years, severe steatosis by ultrasound, and/or body mass index >30 kg/m², partial liver, or hepatitis C (HCV) or B virus positivity.

Results

Characteristics of the study group were a median age of 55 years (range, 27-68 years), HCV positivity in 164 patients (54%), HCC in 134 patients (44%), partial liver use in 25 (8%), MELD 15 (range, 6-40), D-age of 56 years (range, 18-87 years), and median D-MELD score 826 (range, 126-2,988). Overall graft survival was 84%, 79%, and 77% at 1, 3, and 5 years after LT, respectively. Logistic regression did not show a significant correlation between graft failure and D-MELD score in the absence of a significant D-MELD cutoff. Cox regression with D-MELD as the continuous variable showed a hazard ratio (HR) of 0.99 (95% confidence interval [CI], 0.99-1.00; P = NS); and with D-MELD as a dichotomic variable (≥0 to <1,600) an HR of 0.98 (95% CI, 0.63-1.77; P = NS).

Conclusion

The prognostic ability of D-MELD fails in OLT centers that use a more complex D-R matching policy.     

CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions

Background

Obstructive jaundice is frequently associated with false CA19-9 elevation in benign conditions. The diagnostic accuracy of this tumor marker was evaluated in the present longitudinal study.

Methods

In 128 patients admitted for obstructive jaundice (87 with pancreato-biliary malignancy and 41 benign disease) serum CA19-9 was measured. Statistical analysis of marker levels obtained before and after endoscopic biliary drainage was performed in 60 patients.

Results

Elevated CA19-9 levels (>37 U/mL) were found in 61% of benign cases and 86% of malignancies. After biliary drainage, decrease of serum CA19-9 was observed in 19 of 38 malignant cases and in almost all benign cases (Wilcoxon matched pairs test: P = .207 and P <.001, respectively). Receiver operating characteristic (ROC) analysis identified a cut-off value of 90 U/mL to be associated with improved diagnostic accuracy after biliary drainage (sensitivity 61%, specificity 95%).

Conclusions

In the presence of successfully drained obstructive jaundice, CA19-9 serum levels that remain unchanged or measure more than 90 U/mL are strongly indicative of a malignant cause of obstruction. However, the real clinical utility of this marker remains controversial.     

Should Idiopathic Facial Aseptic Granuloma Be Considered Granulomatous Rosacea? Report of Three Pediatric Cases

Abstract: Idiopathic facial aseptic granuloma (IFAG), or pyodermite froide du visage, is a skin disease reported only in children and characterized by painless red nodules usually located on the cheeks. Its etiology is still unclear, but some authors considered the possibility that IFAG might be included in the spectrum of granulomatous rosacea (GR). The histopathological features of IFAG and GR are quite similar, showing perifolliculitis, granulomas, folliculitis, and lymphocytes and plasmacells around epithelioid histiocytes. In the present article, we discuss three cases in which an association between a facial nodule, compatible with both IFAG and GR, and recurrent chalazia make us support the hypothesis that IFAG should be considered as GR.     

White-line: A new finding in laryngopharyngeal reflux objective evaluation

Laryngopharyngeal reflux (LPR) indicates the reflux-induced extra-esophageal disorders. LPR and gastroesophageal reflux disease (GERD) occur by the same mechanism: the escape of gastric contents into the esophagus and beyond. However, the classic GERD symptoms are not typical in LPR disease, which can cause a lot of symptoms none of which is specific, making the diagnosis often elusive. The protective mechanisms present in the esophagus are entirely lacking in the larynx, and more generally in upper aerodigestive tract, making them particularly vulnerable to injury from acidic gastric contents. Since gastric acid backflow can affect supraesophageal structures, even in the absence of heartburn or regurgitation symptoms, an early diagnosis is important to prevent the onset of histological modifications in the supraesophageal mucosa.     

Arthroscopic-assisted focal resurfacing of the knee: surgical technique and preliminary results of 13 patients at 2 years follow-up

Purpose  

The purpose of this study is to describe an arthroscopic-assisted surgical technique for focal resurfacing of medial tibio-femoral compartment and to present the preliminary clinical and radiographic results in a case series of 13 consecutive patients at a mean follow-up of 29 months.     

CT colonography versus double-contrast barium enema for screening of colorectal cancer: comparison of radiation burden

Our aim is to compare the radiation dose associated with a low-dose CT colonography (CTC) protocol for colorectal cancer screening with that delivered by double-contrast barium enema (DCBE). CTC of twenty asymptomatic individuals (M:F = 10:10) participating to a colorectal cancer screening program and DCBE of fifteen patients (M:F = 6:9) were evaluated. For CTC, absorbed dose was determined by calculating the dose-length product for each CTC examination from measurements on a CT dose phantom equipped with a CT ion chamber. For DCBE, the free-in-air Kerma at the patient’s X-ray entry surface and the Kerma-area product during fluoroscopy and fluorography were measured with a Barracuda system, with fluoroscopy times being recorded blinded to the performing operator. Effective dose at CTC was 2.17 ± 0.12 mSv, with good and excellent image quality in 14/20 (70%) and 6/20 cases (30%), respectively. With DCBE, effective patient dose was 4.12 ± 0.17 mSv, 1.9 times greater than CTC (P < 0.0001). Our results show that effective dose from screening CTC is substantially lower than that from DCBE, suggesting that CTC is the radiological imaging technique of the large bowel with the lowest risk of stochastic radiation effects.     

Italian neurologists’ perception on cognitive symptoms in major depressive disorder

The assessment of cognition is an important part of major depressive disorder (MDD) evaluation and a crucial issue is the physicians’ perception of cognitive dysfunction in MDD that remains nowadays a little known matter. The present study aims at investigating the understanding of neurologists’ perception about cognitive dysfunction in MDD. An on-line survey addressed to 85 Italian neurologists in the period between May and June 2015 was performed. The questionnaire comprised three sections: the first section collecting information on neurologists’ socio-demographic profile, the second investigating cognitive symptoms relevance in relation with different aspects and the third one explicitly focusing on cognitive symptoms in MDD. Cognitive symptoms are considered most significant among DSM-5 symptoms to define the presence of a Major Depressive Episode in a MDD, to improve antidepressant therapy adherence, patients’ functionality and concurrent neurological condition, once resolved. Furthermore, an incongruity came to light from this survey: the neurologists considered cognitive symptoms a not relevant aspect to choose the antidepressant treatment in comparison with the other DSM-5 symptoms on one side, but they declared the opposite in the third part of the questionnaire focused on cognitive symptoms. Cognitive symptoms appeared to be a relevant aspect in MDD and neurologists have a clear understanding of this issue. Nevertheless, the discrepancy between neurologists’ perception on cognitive symptoms and the antidepressant treatment highlights the feeling of an unmet need that could be filled increasing the awareness of existing drugs with pro-cognitive effects.     

The histone deacetylase inhibitor ITF2357 has anti-leukemic activity in vitro and in vivo and inhibits IL-6 and VEGF production by stromal cells.

We have investigated the activity of ITF2357, a novel hydroxamate histone deacetylase inhibitor, on multiple myeloma (MM) and acute myelogenous leukemia (AML) cells in vitro and in vivo. ITF2357 induced apoptosis in 8/9 MM and 6/7 AML cell lines, as well as 4/4 MM and 18/20 AML freshly isolated cases, with a mean IC(50) of 0.2 microM. ITF2357 activated the intrinsic apoptotic pathway, upregulated p21 and downmodulated Bcl-2 and Mcl-1. The drug induced hyperacetylation of histone H3, H4 and tubulin. When studied in more physiological conditions, ITF2357 was still strongly cytotoxic for the interleukin-6 (IL-6)-dependent MM cell line CMA-03, or for AML samples maximally stimulated by co-culture on mesenchymal stromal cells (MSCs), but not for the MSCs themselves. Interestingly, ITF2357 inhibited the production of IL-6, vascular endothelial growth factor (VEGF) and interferon-gamma by MSCs by 80-95%. Finally, the drug significantly prolonged survival of severe combined immunodeficient mice inoculated with the AML-PS in vivo passaged cell line already at the 10 mg/kg oral dose. These data demonstrate that ITF2357 has potent anti-neoplastic activity in vitro and in vivo through direct induction of leukemic cell apoptosis. Furthermore, the drug inhibits production of growth and angiogenic factors by bone marrow stromal cells, in particular IL-6 and VEGF.