Do carnitine and extra trace elements change stability of paediatric parenteral nutrition admixtures?

INTRODUCTION: High concentrations of trace elements (TE), in particular zinc and selenium, along with carnitine, are often added to parenteral admixtures in paediatric patients on long-term Parenteral Nutrition (PN). We aim to evaluate whether lipid droplet diameters of these admixtures maintain the recommended range of 0.4-1.0 µm. MATERIALS AND METHODS: Stability studies were carried out on six parenteral admixtures with carnitine, trace elements and electrolytes added in different amounts. Each admixture was formulated with five different lipid emulsions with or without fish oil. Analyses were performed at time 0 (t = 0) and 24, 48, 72, 96 (t = 96) hours after compounding. Droplet diameters were determined by Light Scattering-Reverse Fourier Optics Technique. Samples, stored at 4 °C, were triple tested for a total of 450 analyses. Regression analyses were performed using panel-data techniques. RESULTS: During the 4 days, lipid droplet diameters were in the expected range of 0.4-1.0 µm regardless of trace element and carnitine amounts in all admixtures apart from those containing fish-oil based emulsions and calcium concentrations equal to 4.5 mmol/L. In these latter admixtures, 12% of droplet diameters were larger than 1.0 µm and 2% exceeded 5.0 µm immediately after compounding. CONCLUSION: Carnitine and high concentrations of trace elements do not affect PN admixtures stability and can be safely infused in long-term home-PN paediatric patients and prematures. Only high calcium concentrations in compresence with fish oil based lipid emulsions seem to change PN stability.

Hyaluronic acid for treatment of the radiation therapy side effects: a systematic review.

OBJECTIVE: The main limit of radiation therapy is the dose-dependent toxicity to healthy tissues. The 36% of patients exposed to radiotherapy for pelvic malignancies reporting gastrointestinal symptoms as incontinence, pain, mucus discharge, and bleeding (radiation proctopathy). In the cervix cancer, healthy tissues exposed to radiations easily develop inflammation of vaginal mucosa, bleeding and pain and to improve these symptoms, some medical devices were developed. One of the most interesting for its features is undoubtedly the hyaluronic acid. Considering the histological similarity between the vaginal and the rectal mucosa, the application of hyaluronic acid for the radiation proctopathy represents an interesting opportunity. MATERIALS AND METHODS: We performed a literature search of MEDLINE, EMBASE, PubMed, and Research Gate for studies published up to March 2018. The following combination of medical subject headings, terms and free text words were used: 'hyaluronic acid', 'hyaluronate', 'topical application' and 'radiation proctitis'. RESULTS: After the screening of titles and abstracts, and using the established criteria, 7 studies were selected for inclusion in the systematic review. CONCLUSIONS: The clinical use of hyaluronic acid for topical administration in patients with inflammatory conditions at the level of the vaginal and anal mucosa, following radio and chemo-therapies, resulted an innovative approach to help patients in managing the AEs. Hyaluronic acid confirmed its totally safety profile and resulted effective in the inflammation decrease, improving the tissue health and the symptoms related. For all these reasons, we can easily promote the clinical application of hyaluronic acid on inflamed tissues though a substantial work is necessary to investigate more deeply the hyaluronic acid role on this context.

Probiotic mixture supplementation in the preventive management of trinitrobenzenesulfonic acid-induced inflammation in a murine model.

Inflammatory bowel diseases (IBD) are characterized by inflammatory conditions of the intestine. Probiotic bacteria (PB) can have beneficial effects in several gastrointestinal disorders. The objectives of this study were: (i) to provide an acute experimental IBD model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in CD-1 mice, and (ii) to assess the preventive effects of Citogenex (Lactobacillus casei and Bifidobacterum lactis) supplementation on intestinal tissues and microbiota. Mice were inoculated intrarectally with saline, ethanol or different TNBS solutions. 1%TNBS induced clinical signs of colitis (P less than 0.01) and histological damage (P less than 0.01). Based on these results, mice were pre-treated with Citogenex or saline for 1, 2 or 3 weeks before 1%TNBS treatment. Probiotic pre-treatment determined a reduction of clinical signs (P less than 0.05), histological alterations of colitis (P less than 0.05) and increased beneficial bacteria (P less than 0.05). This study confirms that TNBS-induced colitis in CD-1 mice is useful for studying the mechanisms involved in IBD pathogenesis, and pre-treatment with Citogenex prevents the intestinal damage induced by TNBS.

Expression of Bcl-2 in canine osteosarcoma.

Osteosarcoma (OS) is the most common primary malignancy of bone. It is responsible for 80-85% of the primary bone tumors affecting dogs and it is characterized by aggressive and invasive behavior, with a high metastatic potential. Several studies on cancer and related tumorigenesis, show an involvement of the mechanisms of programmed cell death and cell survival. Many signals seem to be involved in the related mechanism of autophagy and in particular, our interest is focused on the expression of a family of Bcl-2 that seems to be involved either in the control of biomolecular mechanisms like autophagy and apoptosis. In this study we investigated the expression of Bcl-2 in different cases of spontaneous canine osteosarcoma and the related preliminary results are described. We found Bcl-2 activity was increased in OS tissue compared to normal bone tissue. These results suggested that Bcl-2 activity may play an important role in the formation of OS and as a diagnostic for neoplastic activity. However, further research is needed to confirm the role of Bcl-2 activity in OS in canines.

Pulmonary masses in a patient with blue-gray cutaneous hyperpigmentation.

Authors describe a case of pulmonary masses and estensive skin pigmentation: "blue-gray syndrome" occurred in a patient in amiodarone therapy who presented with progressive dyspnea, cough, and fever. The diagnosis was suspected by detection of a high attenuation of the pulmonary masses on the nonenhanced chest computed tomography (CT) and lots of foamy macrophages in the bronchoalveolar lavage fluid. Relief of respiratory symptoms and radiological improvement was achieved when amiodarone treatment was stopped.

Intraoperative ultrasound is an effective and preferable technique to localize non-palpable breast tumors.

INTRODUCTION: Non-palpable breast tumors represent an increasing management problem in modern Breast Units. Therefore, a simple and accurate procedure to localize these lesions is needed. To date, the most commonly used technique is wire localization, but there are some disadvantages. METHODS: We conducted a prospective study on patients with malignant or benign non-palpable breast tumors who were surgically treated and underwent intraoperative ultrasound (IOUS) from May 2006 to June 2007. Margins of excision were inked and specifically assessed by the pathologist, and were considered positive if

A standardized sentinel lymph node enhanced pathology protocol (SEPP) in patients with breast cancer.

BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy allows enhanced pathology with serial sections and immunohistochemical analysis of the retrieved node. We present our experience with a simple, practical, pathology protocol. METHODS: We analysed 416 consecutive breast cancer patient who underwent SLN biopsy. These were studied with six couples of sections at three different levels, each stained with hematoxylin-eosin (H/E) and immunohistochemistry (IHC) (MNF 116). RESULTS: With conventional analysis the SLN was positive in 106/416 cases (25%). The addition of serial sections, according to the protocol, allowed diagnoses of micrometastases (MICRO) (n = 22) or isolated tumor cells (ITC) (n = 38) or MICRO (n = 1) in 51/416 patients (14.6%). Specifically, the diagnosis was undertaken at level I (8.9%), level II (4%), or level III (1,6%). The incidence of MICRO or ITC was not different in T1 and T2 cases (13% vs. 15%, P = 0.7). The addition of the third level of analysis added very little both in T1 and T2 cancers (1.3% vs. 3.8%, P = 0.1). CONCLUSIONS: Serial sectioning of the SLN allows diagnosis of MICRO and ITC in a significant percentage of cases. Adoption of our protocol seems practical, as the incidence of level III positivity is extremely low, particularly in T1 cancers, and additional sections would be, therefore, unlikely useful.

Amino acid changes in the attachment G glycoprotein of human respiratory syncytial viruses (subgroup A) isolated in Italy over several epidemics (1997-2006).

The human respiratory syncytial virus (HRSV) is the most important cause of admission to hospital for acute lower respiratory tract infections in infants and young children worldwide. Only few studies have investigated the molecular evolution of HRSV, and none has been conduct ed in Italy. The genetic diversity of the G glycoprotein of 59 subgroup A strains obtained from two clinical centers located in Northern and Central Italy was studied, during seven nonconsecutive epidemic seasons (1997-2006). The nucleotide sequences encompassing 624 bp, at the carboxy terminus of the G glycoprotein gene, were compared to sequences representative of previously defined HRSV genotypes. Phylogenetic analysis indicated that most Italian group A isolates clustered into two different lineages (GA2 and GA5), whereas only few isolates grouped into the other known lineages. Eight positively selected sites were found and it was predicted that serine and threonine of positively selected sites 117 and 262 (respectively) are O-glycosilated. The presence of multiple identical sequences in three lineages (GA1, GA5, and BE/A1) suggests that certain strains are predominant in a given epidemic season. Although most of the sites of the G glycoprotein gene of HRSV-A strains seem invariable because of strong purifying selection, some evolutionary "hot spots" may be present. Since the G glycoprotein is a major target (together with the F glycoprotein) of the HRSV humoral immune response, it is important to provide information about its genetic heterogeneity in order to address better both therapeutic and vaccine strategy.

Survivin and Cyclooxygenase-2 are co-expressed in human and mouse colon carcinoma and in terminally differentiated colonocytes.

In the evolution of colon rectal cancer (CRC) the imbalance between cell proliferation and apoptosis is considered one of the prominent causes of tumor induction and/or progression. In order to establish the role of anti apoptotic proteins in colon cancer development, we studied with immunohistochemical techniques the expression of Survivin in a mouse model of colon carcinogenesis induced by 1,2-dimethyl-hydrazine treatment. In this mouse model Survivin was over-expressed during tumor development, showing a distribution mimicking that described in the correspondent human malignancies. We also correlated Survivin distribution with COX-2 and beta-Catenin expression patterns. The co-localization of COX-2/beta-Catenin/Survivin in the same epithelial cells in tumor samples lends credence to possible in vivo regulatory effects of COX-2 and beta-Catenin on the intracellular Survivin levels in mouse and human colon cancer.

Multicenter evaluation of a new 4th generation HIV screening assay Elecsys HIV combi.

Fourth-generation screening assays which permit a simultaneous detection of human immunodeficiency virus (HIV) antigen and antibody reduce the diagnostic window on average by four days in comparison to third-generation antibody assays. Recently, the new automated Elecsys HIV combi was compared in a multicenter study to alternative fourth- and third-generation assays, p24 antigen test and HIV-1 RNA RT-PCR. A total of 104 serocon-version panels, samples of the acute phase of infection after seroconversion (n = 33), anti-HIV-1 positive specimens (n = 572) from patients in different stages of the disease, 535 subtyped samples from different geographical locations, including group M (subtypes A-J) and group O, anti-HIV-2 positive sera (n = 364), dilutions of cell culture supernatants (n = 60) infected with different HIV-1 subtypes, selected performance panels, 8406 unselected samples from blood donors originating from different blood transfusion centers, 3810 unselected sera from daily routine and from hospitalized patients, 9927 unselected samples from South Africa and 1943 potentially interfering samples were tested with the Elecsys HIV combi. Elecsys HIV combi showed a comparable sensitivity to HIV-1 Ag stand-alone assays for early detection of HIV infection in seroconversion panels. The mean time delay of Elecsys HIV combi (last negative sample + 1 day) in comparison to HIV-1 RT-PCR for 92 panels tested with both methods was 3.23 days. The diagnostic window was reduced with Elecsys HIV combi between 1.56 and 5.32 days in comparison to third-generation assays. The specificity of Elecsys HIV combi in blood donors was 99.80% after repeated testing. Our results show that a fourth-generation assay with improved specificity and sensitivity like the Elecsys HIV combi is suitable for blood donor screening due to its low number of false positives and since it detects HIV p24 antigen with a comparable sensitivity to single antigen assays.

Bone marrow and sentinel lymph node biopsy in patients with breast cancer: from staging to ultrastaging?

Bone marrow (BM) biopsy has been suggested as an independent prognostic tool to improve staging in patients with breast cancer. Two hundred and ten consecutive patients operated for breast cancer from June 2000 to June 2005 who signed an informed consent were enrolled in this protocol. Patients underwent SLN biopsy, and lymph nodes were analysed with serial sections and stained with hematossilin-eosin and immunohistochemistry. At the end of the procedure a BM aspirate from the iliac crest was obtained and 5-10 cc of blood collected. A CEA specific nested reverse transcriptase (RT) polymerase chain reaction (PCR) assay was used to examine BM samples. Results were blinded to both patients and clinicians. The median age of the patients was 56 years (range 34-80), and the median tumor diameter 1,5 cm (range 0.2-4.5). BM aspirates were unsuccessful in ten patients, and RT-PCR was not technically feasible in seventeen women, leaving 183 patients available for analysis of results and follow up. SLN biopsy allowed diagnoses of occult metastases (micrometastases and isolated tumor cells) in 16% of patients (29/183). 25% of T1N0 patients (23/92), 35% of T2N0 patients (6/17), and 44% of N1-2 patients (32/72) were BM+ (p = 0.03). At a median follow up of 35 months 5/122 in the BM- group and 6/61 in the BM+ group have relapsed (p = 0.2), while 1/122 and 4/61 have died of disease (p = 0.04) In conclusion, ultrastaging of breast cancer patients may identify a substantial subgroup of patients N-/BM- who may not require adjuvant chemotherapy, as well as a subgroup N-/BM+ with a decreased survival who may need more aggressive therapies. Further follow-up is needed to confirm this hypothesis, and several studies are under way.

[Hormone-dependence and C-ERBB2: relationship between estrogen receptor expression, estrogen-regulated proteins, and C-ERBB2 in breast carcinoma]. / Ormono-dipendenza e C-ERBB2: rapporto tra espressione dei recettori estrogenici, estrogen regulated proteins e C-ERBB2 nel carcinoma della mammella.

We reviewed 1491 consecutive cases of operated breast cancer between 1999-2004, and found that hormone-dependence, particularly if evaluated with functional markers of the estrogen receptor (estrogen regulated proteins, ERP), is inversely proportional to antigen neu expression. Our data confirms that ERP can give additional information on the probability of response to hormonal therapy.

[Towards the standardization of sentinel lymph node analysis in women with breast cancer]. / Verso una standardizzazione dell'analisi del linfonodo sentinella in donne con cancro della mammella.

Sentinel lymph node biopsy allows enhanced pathology through serial sections and immunohistochemical analysis of the retrieved node, with detection of micrometastases and isolated tumor cells not otherwise recognized. We present our experience with a simple, effective, pathology protocol requiring six couples of sections at three different sentinel lymph node levels. Additional micrometastases or ITC were diagnosed in 51/416 patients (14.6%).

[Does incidence of sentinel lymph node metastasis increase after diagnostic manipulation in women with breast cancer?]. / Aumenta l'incidenza di metastasi nel linfonodo sentinella dopo manipolazione diagnostica in donne con cancro della mammella?

503 patients were retrospectively evaluated to assess whether a previous needle or core biopsy, or surgical surgical excision of the primary tumor are associated with passive dislodgment of tumor cells in the sentinel lymph node, as reported in recent publications. We could not identify any increased incidence of sentinel lymph node micrometastases or isolated tumor cells after diagnostic manipulation of the primary tumor.

[Predictive variables of lymphatic metastasis in breast carcinoma with a diameter below 2 cm]. / Variabili predittive di metastasi linfonodali nei carcinomi mammari di diametro inferiore a cm 2.

The axillary lymph node status of patients with newly diagnosed breast cancer remains the most important prognostic information available at the moment. However, only a minority of patients presents with such node metastases at diagnoses. We reviewed our database and studied 500 consecutive patients with early breast cancer, and found that age inferior to 50 years, high grade, diameter superior to 1 cm, elevated Ki-67, and expression of oncogene p-53 are all factors associated with lymph node metastases.

[Extemporaneous examination of the sentinel lymph node in breast cancer: is the glass half full or half empty?]. / L'esame estemporaneo del linfonodo sentinella nel cancro della mammella: il bicchiere è mezzo pieno o mezzo vuoto?

Intra-operative examination of sentinel LN is controversial. Concordance with definitive exam of SLN in this series was 81%, though only 54% of positive cases were diagnosed. Micrometastases and ITC were usually lost intraoperatively, accounting for 14% of cases. Frozen section and touch prep of the SLN were approximately equivalent. The latter has the advantage of preserving tissue for step-analysis of SLN. The ultimate method of intraoperative analysis of SLN which can combine cost-effectiveness and accuracy needs to be determined.

[Synchronous multiple gastric adenocarcinoma: a clinical case]. / Adenocarcinomi gastrici multipli sincroni: un caso clinico.

The Authors present a case of synchronous double gastric carcinoma in a 75-year-old man. Synchronous multiple gastric carcinoma (SMGC) constitutes 4% to 10% of all gastric cancers. It exhibits several clinicopathological characteristics that differ from those of solitary cancers: SMGC occurs in older people (men more than women); early carcinoma is observed more frequently in SMGC than in solitary cancers; the rate of intestinal type lesions is higher in multiple than in single gastric carcinoma. With regard to the pathogenesis of multiple gastric cancer, the theory proposing a multicentric or independent origin rather than the local or distant spread of one cancer (multifocality) has been favored.

[Cystadenocarcinoma in situ of the urachus: a clinical case]. / Cistoadenocarcinoma in situ dell'uraco: caso clinico.

Urachal carcinoma is a rare neoplasm which represents 0.01% cancers in adults. If this neoplasm is unusual, the development of cystadenocarcinoma on a urachal cyst is still more rare. The surgical treatment of choice is en-bloc excision of umbilicus and median umbilical ligament with partial cystectomy. As the urachal cystadenocarcinoma of Authors' patient was in situ and without bladder-invasion, they performed a more conservative treatment without partial cystectomy. They believe that this treatment may be indicated in association with a close follow-up after surgery.