Italian Patient Research Articles

Establishment and characterization of a human intrahepatic cholangiocarcinoma cell line derived from an Italian patient.

Biliary tract carcinoma is a rare malignancy with multiple causes, which underlie the different genetic and molecular profiles. Cancer cell lines are affordable models, reflecting the characteristics of the tumor of origin. They represent useful tools to identify molecular targets for treatment. Here, we established and characterized from biological, molecular, and genetic point of view, an Italian intrahepatic cholangiocarcinoma cell line (ICC), the MT-CHC01. MT-CHC01 cells were isolated from a tumor-derived xenograft. Immunophenotypical characterization was evaluated both at early and after stabilization passages. In vitro biological, genetic, and molecular features were also investigated. In vivo tumorigenicity was assessed in NOD/SCID mice. MT-CHC01cells retain epithelial cell markers, EPCAM, CK7, and CK19, and some stemness and pluripotency markers, i.e., SOX2, Nanog, CD49f/integrin-α6, CD24, PDX1, FOXA2, and CD133. They grow as a monolayer, with a population double time of about 40 h; they show a low migration and invasion potential. In low attachment conditions, they are able to form spheres and to growth in anchorage-independent manner. After subcutaneous injection, they retain in vivo tumorigenicity; the expression of biliary markers as CA19-9 and CEA were maintained from primary tumor. The karyotype is highly complex, with a hypotriploid to hypertriploid modal number (3n+/−) (52 to 77 chromosomes); low level of HER2 gene amplification, TP53 deletion, gain of AURKA were identified; K-RAS G12D mutation were maintained from primary tumor to MT-CHC01 cells. We established the first ICC cell line derived from an Italian patient. It will help to study either the biology of this tumor or to test drugs both in vitro and in vivo.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-015-4215-3) contains supplementary material, which is available to authorized users.

Pathological and immunological features of autoinflammatory syndrome associated with lymphedema (AISLE)

Background We recently described a new autoinflammatory syndrome associated with lymphedema (AISLE), and a frameshift mutation in the MDFIC gene was identified by homozygosity mapping and targeted sequencing using DNA samples of a consanguineous Turkish family as the cause of this syndrome. The same mutation in the MDFIC gene was identified in an Italian patient with similar clinical findings. Clinical findings of these patients are characterized by recurrent attacks of fever, erythematous/urticarial rash with hyperesthesia, myalgia, serositis, chylous serosal effusions, edema/lymphedema on the face and extremities. These patients gradually developed a permanent lymphedema in the same areas affected during attacks. On the other hand, there is limited information about the functions of MDFIC gene, which include transcriptional regulator interacting with cellular transcription factors, including such as axin and wnt/b-catenin signaling pathway. Although, its expression has been documented in immune cells, no clear function has been described in immune mediated or inflammatory conditions.

On the user's side: definitions in Italian and British patient information leaflets

This article examines patient information leaflets (PILs), as texts addressed by experts to laypersons. The PIL (foglio illustrativo in Italian) is a mandatory document packed with medicines that provide the patient with information about the medicine and instructions on how and when to take it. The paper comparatively analyses the definitions of medical terms in Italian and British PILs. It is based on a qualitative analysis of data extracted from two small comparable corpora consisting of 50 Italian and 50 British texts, respectively. Results have revealed some similarities that seem to be cross-cultural features of the genre, and significant differences.

When Patient and Analyst Speak the “Same” Language: Exploring the Paradoxes of Belonging and Not Belonging

As the title suggests, this presentation explores the paradoxes found in the subjective experiences of belonging and not belonging when solely English-speaking psychoanalysts, like this author, assume they are speaking the “same” language as their bilingual patients for whom English is a secondary language. Seen through the lens of Brandchaft’s conceptualization of “systems of pathological accommodation,” in-depth, clinical vignettes from the analytic journey with her Italian patient, Antonio, illustrate the process by which the emergence of unspeakable traumas, embedded in his mother-tongue language world, bring into the foreground these unforeseen paradoxes. This awareness creates much turbulence in their analytic relationship. Ultimately, however, long-held convictions about their mutual experiences of belonging and not belonging are redefined, and significantly transform their ways-of-being in the world. In conclusion, the analyst describes the emergence of disavowed words and phrases particular to her own history and subsequent realization that paradoxically, none of us is truly monolingual. This in turn, raises questions about why the psychoanalytic world has privileged English: is this is a manifestation of ethnocentricity, or perhaps a means by which we sustain our ties with our psychoanalytic forebears, who, as survivors of the Holocaust, have disavowed horrific, unspeakable memories by silencing their own as well as their patients’ mother tongue?

How do we estimate survival? External validation of a tool for survival estimation in patients with metastatic bone disease-decision analysis and comparison of three international patient populations.

BackgroundWe recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on www.PATHFx.org, we attempted to externally validate it using independent, international data.MethodsWe collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2010 and 2013, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis (DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia).ResultsThe Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon’s estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery.ConclusionsPATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied.

Whole exome sequencing reveals a novel de novo FOXC1 mutation in a patient with unrecognized Axenfeld–Rieger syndrome and glaucoma

We report the identification of a novel mutation in the fork-head box C1 (FOXC1) gene which occurred de novo in an Italian patient with unrecognized Axenfeld–Rieger syndrome. He was previously diagnosed as having late recognized primary congenital glaucoma at the age of 14years and was subsequently subjected to multiple surgical interventions due to uncontrolled intraocular pressure and progressive visual field loss.After exclusion of mutations in CYP1B1 and MYOC, trio-whole-exome sequencing revealed de novo in frame deletion in the coding region of the FOXC1 gene (c.407_409delGTC, p.V137del) leading to a deletion of the evolutionary conserved amino acid Valine at position 137 of the protein. Molecular modeling predicted that Val137 deletion impairs FOXC1 DNA-binding capacity and transcriptional activation.Since loss-of-function mutations in FOXC1 are associated with Axenfeld–Rieger syndrome, the genetic findings in combination with re-evaluation of the patient's clinical data resulted in a corrected diagnosis of Axenfeld–Rieger syndrome with developmental glaucoma. We therefore suggest that in addition to CYP1B1 and MYOC, FOXC1 should be included in the genetic analysis of cases with unclear glaucomatous phenotypes to ensure proper diagnosis, adequate treatment and appropriate genetic counseling.

Italian version of the M.D. Anderson Symptom Inventory--Head and Neck Module: linguistic validation.

Head and neck cancer (HNC) patients can experience symptoms due to the tumor itself or to the treatment, with an impact on health-related quality of life (HRQoL). Patient-reported outcome (PRO) measures pertaining to HRQoL are used in medical research and to support clinical decisions. PRO instrument applicability and cultural adaptation must be tested for each population. The aim of this study is to linguistically validate the Italian translation of the M.D. Anderson Symptom Inventory--Head and Neck Module (MDASI-HN). Following forward and backward translation of the items of the English MDASI-HN into Italian, it was administered along with a cognitive debriefing to HNC patients able to read and understand Italian language. Individual and group responses are presented using descriptive statistics. From May 2013 through September 2013, 56 patients with HNC (18 during curative treatment, 20 in palliative chemotherapy, and 18 in follow-up period) completed the MDASI-HN followed by accompanying cognitive debriefing. Ninety-nine percent of the individual MDASI-HN items were completed. Average time to complete the MDASI-HN was 8.5 min (range 3-15). Results suggested overall ease of completion, relevance, and comprehensibleness of this translated self-report instrument in this Italian patient population. The Italian version of the MDASI-HN is linguistically valid; future research should explore dimensionality, reliability, and convergent, discriminant, and predictive validity of this patient-reported instrument, in order to use this translated version in outcomes research and clinical settings.

Nail Psoriasis in Children: Common or Uncommon Results from a 10-Year Double-Center Study

Purpose of the Study: Our aim was to perform an extensive search of the literature on the prevalence of nail psoriasis in the pediatric population and to estimate it on our own database. Procedures: Searching the most important databases yielded results of 16 papers published in a 40-year period which reported the prevalence of nail psoriasis in children. Furthermore, data gathered between 2004 and 2013 at two centers specialized in nail disorders were analyzed. Results: The selected papers encompassed a total of 4,853 psoriatic children, of whom 762 (15.7%) had nail involvement. Concerning our data, a total of 68,839 children were seen in pediatric skin consultation in both clinics over a period of 10 years, 0.11% of which had nail involvement. The rate of psoriatic children presenting nail alterations was 19.4% in the Greek and 15.5% in the Italian patient groups. Conclusions and Message: This is the retrospective study including the largest number of cases of nail psoriasis in the pediatric population. Our data are in line with the incidence estimation of the rest of Europe.

A multimodal mapping study of conduction aphasia with impaired repetition and spared reading aloud

The present study explores the functional neuroanatomy of the phonological production system in an Italian aphasic patient (SP) who developed conduction aphasia of the reproduction type following brain surgery. SP presented with two peculiar features: (1) his lesion was localized in the superior temporal gyrus, just posterior to the primary auditory cortex and anterior/inferior to and neighboring the Sylvian parietal temporal (Spt) area, and (2) he presented with severely impaired repetition and spelling from dictation of words and pseudowords but spared reading-aloud of words and pseudowords.Structural, functional, fiber tracking and intraoperative findings were combined to analyze SP's pattern of performance within a widely used sensorimotor control scheme of speech production.We found a dissociation between an interrupted sector of the arcuate fasciculus terminating in STG, known to be involved in phonological processing, and a part of the arcuate fasciculus terminating in MTG, which is held to be involved in lexical-semantic processing. We argue that this phonological deficit should be interpreted as a disorder of the feedback system, in particular of the auditory and somatosensory target maps, which are assumed to be located along the Spt area. In patient SP, the spared part of the left arcuate fasciculus originating in MTG may support an unimpaired reading performance, while the damaged part of the left arcuate fasciculus originating in STG may be responsible for his impaired repetition and spelling from dictation.

First report of chronic pulmonary infection by KPC-3-producing and colistin-resistant Klebsiella pneumoniae sequence type 258 (ST258) in an adult patient with cystic fibrosis.

The spread of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae continues to increase, and the possible development of KPC-producing K. pneumoniae infections in cystic fibrosis (CF) patients is a matter of concern. Here, we describe the establishment of a chronic lung infection due to a colistin-resistant KPC-producing K. pneumoniae isolate in an Italian CF patient.

Appropriateness of clinical and organizational criteria for intra-articular injection therapies in osteoarthritis. A Delphi method consensus initiative among experts in Italy.

The aim of the study was to identify the main aspects involved in patient selection, the choice of therapeutic agents and the safety profile, as well as the medico-legal and organizational aspects of intra-articular injection therapies for osteoarthritis. A committee of 10 experts from Italian universities, public hospitals, territorial services, research institutes and patient associations was set up. Fifty-two clinicians from a large number of Italian medical centers specialized in intra-articular injection therapy took part in a Delphi process aimed at obtaining consensus statements among the participants. Large consensus was obtained for statements grouped under the following main themes: treatment indications; drug/medical device choice; treatment efficacy; and appropriate setting. The consensus statements developed by a large number of experts may be used as a practical reference tool to help physicians treat osteoarthritis patients by means of intra-articular injection therapies.

Incidental Finding of a Homozygous p.M348K Asymptomatic Italian Patient Confirms the Many Faces of Cystic Fibrosis.

Cystic fibrosis (CF; OMIM number 219700) is an autosomal recessive disease caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, which results in abnormal viscous mucoid secretions in multiple organs and whose main clinical features are pancreatic insufficiency, chronic endobronchial infection, and male infertility. We report the case of a 47-year-old apparently normal male resulting in homozygosity for the mutation p.M348K from nonconsanguineous parents. The proband was screened using a standard panel of 70 different tested on NanoChip 400 platform. The massive parallel pyrosequencing on 454 JS machine allowed the second level analysis. The patient was firstly screened with two different platforms available in our laboratory, obtaining an ambiguous signal for the p.R347P mutation. For this reason we decided to clarify the discordant result of CFTR status by Next Generation Sequencing (NGS) using 454 Junior instrument. The patient is resulted no carrier of the p.R347P mutation, but NGS highlighted a homozygous substitution from T>A at position 1043 in the coding region, causing an amino acid substitution from methionine to lysine (p.M348K). Casual finding of p.M348K homozygote mutation in an individual, without any feature of classical or nonclassical CF form, allowed us to confirm that p.M348K is a benign rare polymorphism.

Budget impact analysis of apixaban versus other NOACs for the prevention of stroke in Italian atrial fibrillation patients

OBJECTIVE: This study aims to perform a budget impact analysis of the use of three available novel oral anticoagulant agents (NOACs) for preventing thromboembolic events in Italian patients with non‑valvular atrial fibrillation (NVAF).METHODS: Estimated Italian population of patients was run through a previously published lifetime decision tree/Markov model simulating their treatment with the available therapeutic options: dabigatran at two dose levels (110 mg/bid for the over 80 years old, 150 mg/bid for younger NVAF patients), rivaroxaban (20 mg/uid), and apixaban (5 mg/bid). Effectiveness and safety estimates derive from an adjusted indirect treatment comparison using warfarin as link. The main clinical events considered in the model are ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor) and cardiovascular hospitalizations, besides treatment discontinuations. Epidemiological data and unit costs, actualized to 2013, are collected from Italian published sources. The budget impact analysis evaluates the financial impact of apixaban introduction by comparing expected 1,2, and 3 years costs in hypothetical scenarios: with and without apixaban. Italian NVAF patient population estimation is based on official apixaban reimbursement criteria, applying the characteristics of the trial population to national epidemiologic data. Numbers of patients for each regimen are estimated by projecting share evolution. Sensitivity analysis is performed on an alternative non‑experimental population of NVAF patients.RESULTS: Among available NOACs, apixaban was expected to be the least expensive in an estimated patient population of 364,000 Italian patients, allowing for savings of € 1,180,549, € 3,841,429 and € 5,368,918 at 1,2, and 3 years, respectively. Results of the simulation run on an alternative non‑experimental population of NVAF patients yields comparable estimates.CONCLUSIONS: The different safety and effectiveness profiles of the three available NOACs emerging from the adjusted indirect comparison indicate that apixaban could improve health care expenditure control while maintaining or increasing therapeutic appropriateness in the Italian NVAF population.

Primary Cutaneous Small to Medium-Size CD4+ Pleomorphic T-Cell Lymphoma: 48 Patients from Two Independent Centers and Revaluation of Clinico-Histological Criteria for Differential Diagnosis from Other CTCL

Introduction and Background: Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (PC-CD4+ SM-PTL) was recently re-classified as a rare provisional subtype in the 2008 World Health Organization (WHO) classification. It is characterized by solitary nodules or plaques located mostly on the head and neck. Multiple lesions are associated with a worse prognosis; however, the paucity of patients has prevented the definition of prognostic factors. Histologically, a dense cutaneous infiltrate of clonal small/medium hyperchromatic lymphocytes admixed with numerous reactive cells is observed, sometimes leading to the diagnosis of pseudolymphoma or other lymphoma: Mycosis Fungoides (MF) or peripheral T cell lymphoma – not otherwise specified (PTCL-NOS). Differential diagnosis with other aggressive cutaneous lymphomas is very important due to the favorable prognosis of PC-CD4+SM-PTL and complete response to conservative therapies. The purpose of this retrospective study was to evaluate and compare clinical and histological features of PC-CD4+ SM-PTL in 48 cases collected from two independent centers, MD Anderson Cancer Center (Houston, TX) and Dermatological Clinic of the University of Milan (Milan, Italy).Results: Forty-eight patients were identified (26 MDACC and 22 Milan cases). Women out-numbered men (women 67% and 55% respectively, and men 33% and 45% respectively). The mean age at onset was 53 and 50 years. The mean follow-up time was 19 months (1-84 months) for the American group and 31 months (3-180 months) for the Italian group. All patients in both groups were alive at the time of last follow up, without evidence of extra-cutaneous disease.Seventy-four percent of American patients and 73% of Italian patients developed single lesions, most common were nodules in the head and neck area. Multifocal lesions were found in other body sites besides head and neck in 6/7 American patients and in all Italian patients. Multifocal disease was characterized by plaques rather than nodules.Histological features showed a dense infiltrate composed of small to medium-sized hyperchromatic “grouped” atypical lymphoid cells occupying superficial and deep dermis. The infiltrate also showed admixed reactive B-cells, plasma cells, macrophages, and few dendritic cells. Vascular hyperplasia was noted. Adnexotropism was frequently found. Focal epidermotropism was also present. The neoplastic cells were CD3+, CD4+, CD5+, PD1+, CD8-, CD30-. A peculiar perivascular and small cluster arrangement of PD-1+ cells was noted. T-bet nuclear expression was recorded in 3 Italian cases. Mib1/Ki-67 proliferation index was between 5 and 30% in all Italian patients.The treatments used for patients with complete responses included surgical excision, local radiotherapy, and high potency topical steroids, occasionally combined with topical nitrogen mustard. Patients who had complete responses without relapse also had single lesions on the head and neck (67% and 68 % respectively), except for one US patient with multifocal disease. A small group of patients (18.5% and 4%, respectively) relapsed one time. Seven percent of American patients and 18% of Italian patients developed multifocal plaques on the trunk and extremities and had dramatic responses to therapy with a “waxing and waning” course. Only one Italian patient developed rapidly progressive tumors confined mainly to the legs and was resistant to cyclophosphamide and oral steroids.Conclusion: This case series demonstrates that PC-CD4+ SM-PTL is characterized by heterogeneous clinical presentations. There are no definite criteria to predict an aggressive course reported rarely in the literature. Histological findings useful, but not sufficient for diagnosis, and not sufficiently underscored by classical description of this tumor, are the arrangement of PD-1+ atypical cells in small clusters or rosettes surrounding reactive cells and the perivascular distribution of the neoplastic cells. Absent or minimal epidermotropism, a mixed B cell infiltrate and the clinical presentation of a solitary dermal nodule, may help to distinguish PC-CD4+ SM-PTL from the other CD4+ PD1+ CTCLs, mycosis fungoides and PTCL-NOS. DisclosuresNo relevant conflicts of interest to declare.

4A syndrome: ocular surface investigation in an Italian young patient

BackgroundAllgrove’s 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient.Case presentationAn 18-years-old male Caucasian patient, with a complex progressive gait disorder and adrenal insufficiency, was referred for ophthalmic evaluation, as part of the clinical assessment. He underwent the following tests: best corrected visual acuity, tear osmolarity, tear film break-up time (BUT), corneal fluorescein staining, Schirmer’s I test, lid margin assessment, corneal sensitivity, in vivo corneal confocal microscopy, conjunctival impression cytology, tonometry and fundus exam. A dry eye condition was documented by the Schirmer’s I test of 0 mm/5’ in both eyes, accompanied by tear hyperosmolarity, mild meibomian gland dysfunction, reduced BUT, mucus filaments in the tear film and conjunctival epithelium metaplasic changes. The corneal confocal microscopy showed the presence of activated keratocytes, while the nerve pattern was normal.ConclusionsThe dry eye in this patient appears to be due to tear aqueous deficiency and can be considered as part of the 4A syndrome. The decreased tear production, resulting from a deterioration of the autonomic innervation of the lacrimal glands rather than an impaired corneal innervation, can be considered as part of the systemic autonomic dysfunction present in this disease.

The ART Score Is Not Effective to Select Patients for Transarterial Chemoembolization Retreatment in an Italian Series

Background: The ART score (a point score for the assessment of retreatment with transarterial chemoembolization, TACE) has been recently developed in Austria to differentiate patients who may benefit from multiple sessions of TACE for hepatocellular carcinoma (HCC) treatment. The primary aim of the study was to test the validity of the ART score in an Italian study cohort. The secondary aims were to evaluate overall survival (OS) and clinical determinants of improved survival in patients treated with multiple TACE sessions. Methods: The ART score and the clinical outcome of 51 consecutive patients with HCC submitted to multiple TACE sessions from April 2002 to December 2009 were retrospectively analyzed. Results: Median OS was 26.0 months (95% confidence interval 18.4-33.6) with 1-, 3- and 5-year survival rates of 75, 33 and 11%, respectively). Thirty-three patients had an ART score of 0-1.5 and in 18 it was ≥2.5, but in our patient series, the ART score was not found to be a predictor of survival (p = 0.173). At univariate analysis, tumor extent (uni- vs. bilobar: 34.0 vs. 9.0 months; p < 0.001), Child-Pugh score before the second TACE (A vs. B7 vs. B8-9: 26.0 vs. 16.0 vs. 5.0 months; p = 0.005) and Child-Pugh score increase between the first and second TACE (absent vs. + 1 point vs. + ≥2 points: 27.0 vs. 4.0 vs. 5.0 months; p < 0.001) were statistically related with survival. At multivariate analysis, only Child-Pugh score increase remained a significant predictor of worse survival (p = 0.001, hazard rate = 11.6). Conclusions: The ART score was not found to work as an objective tool to guide TACE retreatment in our Italian patient series, only the Child-Pugh score increase was an independent predictor of a shorter survival.

Lack of association between serotonin transporter 5-HTT gene polymorphism and endometriosis in an Italian patient population.

BackgroundThe aim of this study was to determine whether the serotonin transporter gene (5-HTT), a key component in the control of the serotonergic system, is associated with endometriosis in an Italian population.FindingsA case–control study, comprising 137 Italian patients with surgically confirmed endometriosis and 120 healthy controls, was carried out. 5-HTT genotypes (LL, SL and SS) were obtained by polymerase chain reaction and gel electrophoresis analysis. We found no overall difference in genotypic and allelic distributions of the 5-HTT gene between cases and controls.ConclusionsOur results suggest that the 5-HTT L/S promoter polymorphism is not associated with susceptibility to endometriosis in the studied Italian patients.

Influence of the HLA characteristics of Italian patients on donor search outcome in unrelated hematopoietic stem cell transplantation.

The information regarding the probability of finding a matched unrelated donor (MUD) within a relatively short time is crucial for the success of hematopoietic stem cell transplantation (HSCT), particularly in patients with malignancies. In this study, we retrospectively analyzed 315 Italian patients who started a search for a MUD, in order to assess the distribution of human leukocyte antigen (HLA) alleles and haplotypes in this population of patients and to evaluate the probability of finding a donor. Comparing two groups of patients based on whether or not a 10/10 HLA-matched donor was available, we found that patients who had a fully-matched MUD possessed at least one frequent haplotype more often than the others (45.6% vs 14.3%; P = 0.000003). In addition, analysis of data pertaining to the HLA class I alleles distribution showed that, in the first group of patients, less common alleles were under-represented (20.2% vs 40.0%; P = 0.006). Therefore, the presence of less frequent alleles represents a negative factor for the search for a potential compatible donor being successful, whereas the presence of one frequent haplotype represents a positive predictive factor. Antigenic differences between patient and donor observed at C and DQB1 loci, were mostly represented by particular B/C or DRB1/DQB1 allelic associations. Thus, having a particular B or DRB1 allele, linked to multiple C or DQB1 alleles, respectively, might be considered to be associated with a lower probability of a successful search. Taken together, these data may help determine in advance the probability of finding a suitable unrelated donor for an Italian patient.

Atypical Presentation of PKDL due to Leishmania infantum in an HIV-Infected Patient with Relapsing Visceral Leishmaniasis.

We describe the case of an Italian patient with HIV infection who developed an atypical rash resembling post-kala-azar dermal leishmaniasis (PKDL) when receiving liposomal Amphotericin B (L-AMB) for secondary prophylaxis of visceral leishmaniasis (VL). At the time of PKDL appearance, the patient was virologically suppressed but had failed to restore an adequate CD4+ T-cell count. Histology of skin lesions revealed the presence of a granulomatous infiltrate, with lymphocytes, plasma cells, and macrophages, most of which contained Leishmania amastigotes. Restriction fragment length polymorphism-polymerase chain reaction was positive for Leishmania infantum. Paradoxically, cutaneous lesions markedly improved when a new relapse of VL occurred. The patient received meglumine antimoniate, with a rapid clinical response and complete disappearance of cutaneous rash. Unfortunately, the patient had several relapses of VL over the following years, though the interval between them has become wider after restarting maintenance therapy with L-AMB 4 mg/kg/day once a month. Even if rare, PKDL due to Leishmania infantum may occur in Western countries and represents a diagnostic and therapeutic challenge for physicians. The therapeutic management of both PKDL and VL in HIV infection is challenging, because relapses are frequent and evidence is often limited to small case series and case reports.

Cost-effectiveness of omega-3 fatty acid supplements in parenteral nutrition therapy in hospitals: A discrete event simulation model

A recent meta-analysis showed that supplementation of omega-3 fatty acids in parenteral nutrition (PN) regimens is associated with a statistically and clinically significant reduction in infection rate, and length of hospital stay (LOS) in medical and surgical patients admitted to the ICU and in surgical patients not admitted to the ICU. The objective of this present study was to evaluate the cost-effectiveness of the addition of omega-3 fatty acids to standard PN regimens in four European countries (Italy, France, Germany and the UK) from the healthcare provider perspective. Using a discrete event simulation scheme, a patient-level simulation model was developed, based on outcomes from the Italian ICU patient population and published literature. Comparative efficacy data for PN regimens containing omega-3 fatty acids versus standard PN regimens was taken from the meta-analysis of published randomised clinical trials (n = 23 studies with a total of 1502 patients), and hospital LOS reduction was further processed in order to split the reduction in ICU stay from that in-ward stays for patients admitted to the ICU. Country-specific cost data was obtained for Italian, French, German and UK healthcare systems. Clinical outcomes included in the model were death rates, nosocomial infection rates, and ICU/hospital LOS. Probabilistic and deterministic sensitivity analyses were undertaken to test the reliability of results. PN regimens containing omega-3 fatty acids were more effective on average than standard PN both in ICU and in non-ICU patients in the four countries considered, reducing infection rates and overall LOS, and resulting in a lower total cost per patient. Overall costs for patients receiving PN regimens containing omega-3 fatty acids were between €14 144 to €19 825 per ICU patient and €5484 to €14 232 per non-ICU patient, translating into savings of between €3972 and €4897 per ICU patient and savings of between €561 and €1762 per non-ICU patient. Treatment costs were completely offset by the reduction in hospital stay costs and antibiotic costs. Sensitivity analyses confirmed the robustness of these findings. These results suggest that the supplementation of PN regimens with omega-3 fatty acids would be cost effective in Italian, French, German and UK hospitals.