Risks and limits of bariatric surgery: old solutions and a new potential option.

The present review focuses on the side effects that ex-obese patients face following bariatric surgery. We searched through the principal medical indexes (SCOPUS, Web of Science, PubMed, MEDLINE) using the following words, both alone and in combinations: bariatrics; bariatric surgery; anemia; vitamin B12; cobalamin; folate; folic acid; iron; iron supplements; gut microbiota; lactalbumin; α-lactalbumin. To perform exhaustive research, we considered articles published since 1985. Bariatric surgery induces states of nutritional deficiencies. In particular, the surgery results in a drastic fall in the levels of iron, cobalamin, and folate. Despite the dietary supplements which can counteract such decrease, some limitations exist in the nutraceutical approach. Indeed, the gastrointestinal side effects of supplements, the alterations in the microbiota, and the reduced absorption induced by the surgery may impair the effect of dietary supplements, exposing the patients to the risk of developing nutritional deficiencies. Recent literature reports the effect of promising molecules to counteract such limitations, which include α-lactalbumin, a whey protein with prebiotic activities, and new pharmaceutical forms of iron supplements, namely micronized ferric pyrophosphate. If on the one hand, α-lactalbumin enhances intestinal absorption and helps in restoring a physiological microbiota, micronized ferric pyrophosphate has a high tolerability and low or null risk of gastrointestinal side effects. Bariatric surgery represents a valid solution to obesity and obesity-related disease. However, the procedure may induce deficiencies in micronutrients. Data exists on the promising activities of α-lactalbumin and micronized ferric pyrophosphate, which may help in preventing bariatric-induced anemia.

Central nervous system bleeding in patients with rare bleeding disorders.

Central nervous system (CNS) bleeding is one of the most severe and debilitating manifestations occurring in patients with rare bleeding disorders (RBDs). The aim of this study was to retrospectively collect data on patients affected with RBDs who had CNS bleeding, to establish incidence of recurrence, death rate, neurological sequences, most frequent location, type of bleeding and efficacy of treatments. Results pertained to 36 CNS bleeding episodes in 24 patients with severe deficiency except one with moderate factor VII (FVII) deficiency. Six patients (25%) experienced a recurrence and two had more than one recurrence. Seven patients (29%) had an early onset of CNS bleeding before the first 2 years of life, others (71%) later in life. In 76% of cases, CNS bleeding was spontaneous. CNS bleeding was intracerebral in 19 cases (53%), extracerebral in 10 (28%) and both intracerebral and extracerebral in two cases (6%). Neurosurgery was performed in 11 cases, in association with replacement therapy in seven cases. Seizures were noted in four patients. Residual psychomotor abnormalities were seen in two patients. No death was recorded. To prevent recurrence, 17/24 patients (71%) were put on secondary prophylaxis. In conclusion, recurrence of CNS bleeding was confirmed to be relatively frequent in patients with severe FV, FX, FVII and FXIII deficiencies. Most patients were managed with replacement therapy alone, surgery being reserved for those with worsening neurological conditions. Our results indicate that some RBDs require early prophylactic treatment to prevent CNS bleeding. Optimal dosage and frequency of treatment need further evaluation.

Prevalence of allo-immunization anti-HLA and anti-integrin alphaIIbbeta3 in Glanzmann Thromboasthenia patients.

SUMMARY: Platelet transfusions, main therapy of Glanzmann Thromboasthenia (GT), can induce an allo-immunization against human leucocyte antigen and integrin alphaIIbbeta3. We have investigated in our GT patients the rate of allo-immunization and of refractoriness to platelet transfusions. From 1975 until December 2005, we have followed 17 GT patients: 14 type 1, 3 variant type; nine females, eight males; median age at diagnosis 9.8 years (range 1-44.5); median age at the time of the study 35.5 years (range 23.6-68.5). In our patients, 121 bleeding episodes occurred (24 severe, 37 moderate, and 60 mild). Ten major and 22 minor surgical procedures have been performed. Two spontaneous deliveries and three caesarian sections with five live births were performed; moreover, one late foetal loss occurred, and one voluntary abortion was performed. Sixteen of 17 patients have been transfused at least once in life with platelets and/or red blood cells (RBC). All transfused patients have been investigated for the presence of anti-HLA and anti-integrin alphaIIbbeta3 allo-antibodies. The positiveness of allo-antibodies has been demonstrated in 4/16 transfused patients (25%): isolated for anti-HLA in two; isolated for anti-integrin alphaIIbbeta3 in one; and combined in one. In spite of the presence of allo-antibodies, platelet transfusions have always been effective and the haemostasis was not compromised.

Mortality and causes of death in Italian persons with haemophilia, 1990-2007.

Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co-morbidities in Italian persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died between 1980 and 2007 were retrospectively collected in the 30 centres who are members of the Italian Association of Haemophilia Centres that chose to participate. The mortality rate ratio standardized to the male Italian population (SMR) was reduced during the periods 1990-1999 and 2000-2007 such that during the latter, death rate overlapped that of the general population (SMR 1990-1999: 1.98 95% CI 1.54-2.51; SMR 2000-2007: 1.08 95% CI 0.83-1.40). Similarly, life expectancy in the whole haemophilic population increased in the same period (71.2 years in 2000-2007 vs. 64.0 in 1990-1999), approaching that of the general male population. While human immunodeficiency virus infection was the main cause of death (45%), 13% of deaths were caused by hepatitis C-associated complications. The results of this retrospective study show that in Italian PWH improvements in the quality of treatment and global medical care provided by specialized haemophilia centres resulted in a significantly increased life expectancy.

Performance of recalibrated ReFacto laboratory standard in the measurement of FVIII plasma concentration via the chromogenic and one-stage assays after infusion of recalibrated ReFacto (B-domain deleted recombinant factor VIII).

The use of ReFacto Laboratory Standard (RLS) in the one-stage clotting assay was proposed to reduce the underestimation of factor VIII (FVIII) plasma concentration after the infusion of 'ReFacto' (B-domain deleted recombinant FVIII) in haemophilia A patients. Both ReFacto and RLS were recently recalibrated, with the resulting materials containing approximately 20% more protein than the previous products. The aim of this study was to evaluate the performance of recalibrated RLS in the measurement of FVIII plasma concentration after the infusion of recalibrated ReFacto. In 13 severe haemophilia A patients, 25 IU kg(-1) of ReFacto were injected intravenously. Venous blood samples were collected at 0.25, 0.5, 1, 3, 6, 9, 24, 28 and 32 h after the end of the infusion. Pharmacokinetic parameters were measured for the chromogenic and one-stage assays using International Plasma Standard (IPS) and RLS for both assays and assuming a non-compartmental drug disposition. Comparisons among assays and standards were performed using anova. Pharmacokinetic estimates obtained with the chromogenic method were in agreement with those published in the literature. The one-stage method was confirmed to be more sensitive to lower plasma concentrations of FVIII. The measured maximum plasma concentration (C(max)) was slightly higher than theoretical values and independent of the assay used. C(max), area under the curve (AUC) and volume of distribution at steady state (V(ss)) presented non-significant differences among the methods and standards used. The clinical utility of RLS in the evaluation of FVIII concentration after the infusion of ReFacto seems to be reduced since recalibration of the product.

Discontinuation of imatinib therapy after achievement of complete molecular response in a Ph(+) CML patient treated while in long lasting complete cytogenetic remission (CCR) induced by interferon.

Imatinib has become the gold standard therapy for Ph(+) CML, as it induces complete cytogenetic remission (CCR) in 75-90% of patients in chronic phase (CP), and up to 40% of these patients obtain at least a 3 log reduction of BCR/ABL transcript [Kantarjian HM, Cortes JE, O'Brien S, Luthra R, Giles F, Verstovsek S, et al. Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-alpha. Blood. 2004;104:1979-1988]. However, it is not yet stated whether continued therapy is required to maintain this response or whether imatinib may be discontinued after confirmation of a prolonged complete molecular remission (CMR). We here report on a Ph(+) CML case in long lasting CCR following interferon-alpha treatment (IFN) which reached CMR with imatinib but soon relapsed at molecular level after this latter drug discontinuation; we considered the present observation also in the light of previously reported data.

[Experience of a peripheral center in the surgical treatment of hepatic metastasis from colorectal cancer]. / Esperienza di un centro periferico nel trattamento chirurgico delle metastasi epatiche da cancro colorettale.

Surgical resection is still the first therapeutic option in patients with resectable colorectal cancer metastatic to the liver. Application of radiofrequency energy has been used in patients who did not meet the criteria for resectability and yet were candidates for a liver-directed procedure based upon the presence of liver-only disease. Hepatic resection has evolved in the last two or three decades from a procedure with associated mortality rate of up to 20% in the early 80s to usually less than 5% in patients undergoing liver resection thereafter. This improvement in morbidity and mortality is multifactorial; despite the increased safety of liver operations, hepatic resection still remains a complex surgical procedure with serious potential morbidity. The experience with liver resections and/or radiofrequency ablations, for colorectal cancer metastatic to the liver, performed at a medium-volume center (15 cases in 4 years) is presented. Some features of the metastatic disease, including the number, size and location of metastases are identified. The perioperative mortality is 0, morbidity for non surgical complications is 40%. In this series the reported overall 1-yr survival is 80%, 2-yr is 67%. This paper reviews the experienced factors that have defined the morbidity and mortality associated with liver surgery.

Antiviral susceptibility testing-flow cytometric analysis (AST-FCA) for the detection of cytomegalovirus drug resistance.

Antiviral susceptibility testing-flow cytometric analysis (AST-FCA), an application of flow cytometry in conjunction with cell culture, was developed to identify susceptibility of cytomegalovirus (CMV) isolates to the antiviral drugs ganciclovir (GCV) and foscarnet (PFA). The viral isolates used in this study were obtained from peripheral blood of AIDS patients. Among GCV-susceptible strains, the mean 50% inhibitory concentration (IC50) using AST-FCA was 18 microns (SI50 = 1.4). Among GCV resistant strains, the mean IC50 was 47 microns (SI50 = 3.6). For PFA, the mean IC50 was 80 microns (SI50 = 1.0) for susceptible strains. IC50s for strains resistant to PFA, showed no significant reduction of infectivity at the highest drug concentration (i.e., 200 microns PFA) tested. Additional analyses confirmed the accuracy of AST-FCA by parallel testing using plaque reduction assay. AST-FCA is a novel, nonisotopic, and relatively simple to perform laboratory procedure for the identification of CMV drug-resistant strains.

Aluminosilicates enhance the infectivity of cytomegalovirus in urine using centrifugation-enhanced antigen detection technology.

Due to the inherent lability of CMV, necessary laboratory identification of this infectious agent is often compromised by a delay in specimen transport. Previous studies have addressed the phenomenon of infectivity enhancement/reduction in the rate of infectivity loss by the incorporation into various viral assay systems of trace concentrations of the adsorbents montmorillonite (bentonite [M]) or kaolinite (kaolin [K]). We extended these studies to the clinical setting to identify whether such aluminosilicates would effect an enhanced level of CMV infectivity. The shell vial assay-indirect immunofluorescent assay (SVA-IFA) was utilized in comparative testing throughout this study. The addition of trace concentrations of M or K to the SVA-IFA was found to enhance the infectivity of CMV in urine by 115 and 126%, respectively. The total CMV detection rate by SVA-IFA was 29% (30/105). Three of the 30 (10%) CMV positive specimens were detected only in shell vials which had been supplemented with K or M. Two specimens were isolation positive alone. The addition of K or M to shell vials immediately prior to the start of the SVA-IFA has the potential of (a), enhancing assay readability by increasing the number of fluorescent focus units per vial monolayer and (b), of detecting positive urine specimens with low viral titers which might otherwise not be identified using the conventional SVA-IFA procedure.

[Crohn's disease and intestinal carcinoma: presentation of 2 cases and review of the literature]. / Malattia di Crohn e carcinoma intestinale: presentazione di due casi e rassegna della letteratura.

We present the cases of two patients with Crohn's disease with consequent adenocarcinoma of the bowel. The first patient underwent an ileo-colic bypass 23 years before, a mucinous adenocarcinoma (Duke's stage C) was found on the anastomotic tract and on the excluded bowel, in areas within histologically recognizable Crohn's disease. In the second patient both the adenocarcinoma (Duke's stage C) of the transverse colon and the Crohn's disease (without any clinical evidence) in active phase has been found at the same time. We underline that such association seems to be not so rare as it seemed in the past. Accurate observation of patients, long time sufferers from the Crohn's disease, is advised to single out possible neoplastic complications at an early stage.

[Lipoma of the colon. Its clinical significance and treatment]. / Il lipoma del colon. Significato clinico e trattamento.

The authors present the observation of a case of lipoma of the transverse colon. They review the latest literature confirming the rarity of this case and its clinical importance for diagnostic and therapeutic problems that it could give.

Antiviral susceptibility testing of cytomegalovirus from primary culture using shell vial assay to detect the late viral antigen.

Susceptibility testing of 68 cytomegalovirus (CMV) peripheral blood isolates to Ganciclovir (DHPG) and 11 blood isolates to Foscarnet (PFA), was performed on primary culture isolates using the shell vial assay methodology (SVA-IFA, that is, quantitation of fluorescent focus units, FFUs), with an anti-CMV monoclonal antibody to the late viral antigen. A positive reaction in monolayer cultures of MRC-5 cells was characterized by cytoplasmic fluorescence with inclusions at both or more commonly off one end of the elongated fibroblast nucleus. Isolates from conventional MRC-5 tube cultures displaying a 1+ (10% cytopathic effect) were inoculated into shell vials containing DHPG concentrations of 0, 1.5, 3, 6, 12, or 24 microliters/ml shell vials containing 400, 500, 800, or 1200 microM PFA. The optimal readability of monolayers (expressed as FFUs per monolayer) occurred at 96 h after treatment with DHPG and at 36-48 h with PFA. Resistance to DHPG was determined at the concentration of antiviral agent necessary to reduce the number of FFUs to 90% or 50% of the control [that is, the 90% minimum inhibitory concentration (MIC90) or MIC50]. Six of 68 isolates showed an MIC90 > 12 or an MIC50 > 1.5 microgram/ml, and were considered DHPG resistant. Three of the six isolates were from AIDS patients with late-stage disease who had never received DHPG therapy. All but one (specimen 2400) DHPG-resistant isolates revealed MIC90 values to a PFA concentration of 500 microM, which is considered an achievable peak plasma level in patients undergoing PFA therapy. The single DHPG- and FPA-resistant isolate was obtained from a patient displaying marked clinical resistance to both drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

[Postoperative septic complications in patients operated on for thoracic neoplasms]. / Le complicanze settiche postoperatorie nei pazienti operati per neoplasie del torace.

The authors executed a prospective clinic study evaluating, whether at the admittance or after surgery, the immunity status of 30 patients with a thoracic neoplasm, admitted to Department of Thoracic Surgery, I School of Medicine, Naples. Only 21 of them, immunodepressed at the admittance, were accepted to trial and assigned respectively to A Group destined to surgery (10 patients) and to B check Group (11 patients). In the A Group the effectiveness of the immunotherapy was valued in the prophylaxis and in the postoperative septic complications' therapy. The global incidence of those complications was of 6 cases, of which 10% only in A Group and 45% in B Group. In the operated patients the septic complications had few repercussions on general status and were rapidly and totally dominated in strict correlation with an adequate immunoreconstitution.

Cutaneous leishmaniasis in mice: resistance to glucan immunotherapy, either alone or combined with chemotherapy.

Leishmania braziliensis, L. mexicana, and L. garnhami were studied for their ability to produce American cutaneous leishmaniasis, using C57BL/6 female mice as the animal model. No significant difference in the clinical course of mouse foot pad infection was found between the three American Leishmania species studied. In general, the incubation period varied from 2-4 weeks. Mice developed only local swelling and sometimes ulceration at the sites of inoculation. After 4 weeks of progress lesions began to decrease without obvious impact on the general health of the mice. When glucan immunotherapy (120 - 240 mg/kg body weight) was initiated previous to, or simultaneously with, infection the development of foot pad lesions was not significantly inhibited, this despite clear evidence of generalized stimulation of the reticuloendothelial system. On the other hand, pentavalent antimony at high doses (1,000 - 1,500 mg/kg) induced only a significant lengthening of the latent period. However, different combinations of glucan and pentavalent antimony (various doses of each drug, timing of administration, or changes in the sequence of use of both drugs) did not significantly alter the clinical course of American Leishmania infection as compared with pentavalent antimony alone. Thus, not only were glucan or glucantime alone unable to cure the infection (as evidenced by some animals which showed rapidly growing lesions some time after the end of treatment), but no potentiation was observed.

Permeability of the bladder mucosa to thiotepa, adriamycin, and daunomycin in men and rabbits.

The permeability of the bladder mucosa to thiotepa and to the anthraquinonic antibiotics, adriamycin and daunomycin, was investigated both in humans and in experimental animals. Instillations in rabbits were performed either in intact males or in animals with ligated ureters. Absorption of thiotepa was significantly higher than that of the antibiotics both in men and in rabbits. Furthermore, a qualitative difference was observed in rabbits in relation to time and with regard to fixation to vesical tissues. In man, absorption was highest after transurethral surgery. It was also increased in cases with extensive anaplastic tumours or in the presence of acute inflammatory reactions.