Percutaneous nephrostomy catheter-related infections in patients with gynaecological cancers: a multidisciplinary algorithmic approach.

BACKGROUND: Percutaneous nephrostomy catheters (PCNs) are commonly utilized in patients with gynaecological cancers due to intrinsic or extrinsic urinary obstruction. Unfortunately, these foreign medical devices may be associated with several infectious complications, including: pyelonephritis, renal abscess, and bacteraemia, which may lead to further delay of life-saving cancer therapy. AIM: To evaluate the performance of our multidisciplinary algorithm for diagnosis and treatment of PCN-related infections (PCNIs) and identify risk factors for recurrent urinary device-related infections. METHODS: Patients with gynaecological cancers having PCNIs were prospectively evaluated at our institution from July 2019 to September 2021. All patients were managed by our standardized algorithm and followed-up until reinfection or routine PCN exchange. FINDINGS: Of 100 consecutive patients with PCNIs, 74 had adequate follow-up, and were analysed in three groups according to clinical outcome: reinfection with the same organism (26%), reinfection with a different organism (23%), and no reinfection (51%). Their median age was 54 years, and the most common cancers were cervical (65%), and ovarian (19%) with 53% being metastatic. The most frequently recovered micro-organisms were Pseudomonas (32%), Enterococcus (27%), and Escherichia (24%) species. The main risk factors for recurrent PCNI with the same organism were pelvic radiation therapy (P=0.032), pelvic fistulas (P=0.014), and a PCNI with the same pathogen within the previous year (P = 0.012). CONCLUSIONS: Our algorithm has allowed for accurate diagnosis, staging, and treatment of and identification of several key risk factors for recurrent PCNIs. These results may lead to further preventive measures for these infections.

Atorvastatin prevents lipopolysaccharide-induced depressive-like behaviour in mice.

Clinical and pre-clinical evidences indicate an association between inflammation and depression since increased levels of pro-inflammatory cytokines are associated with depression-related symptoms. Atorvastatin is a cholesterol-lowering statin that possesses pleiotropic effects including neuroprotective and antidepressant actions. However, the putative neuroprotective effect of atorvastatin treatment in the acute inflammation mice model of depressive-like behaviour has not been investigated. In the present study, we aimed to investigate the effect of atorvastatin treatment on lipopolysaccharide (LPS) induced depressive-like behaviour in mice. Mice were treated with atorvastatin (1 or 10 mg/kg, v.o.) or fluoxetine (30 mg/kg, positive control, v.o.) for 7 days before LPS (0.5 mg/kg, i.p.) injection. Twenty four hours after LPS infusion, mice were submitted to the forced swim test, tail suspension test or open field test. After the behavioural tests, mice were sacrificed and the levels of tumour necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), glutathione and malondialdehyde were measured. Atorvastatin (1 or 10 mg/kg/day) or fluoxetine treatment prevented LPS-induced increase in the immobility time in the forced swim and tail suspension tests with no alterations in the locomotor activity evaluated in the open field test. Atorvastatin (1 or 10 mg/kg/day) or fluoxetine treatment also prevented LPS-induced increase in TNF-α and reduction of BDNF levels in the hippocampus and prefrontal cortex. Treatment with atorvastatin (1 or 10 mg/kg/day) or fluoxetine prevented LPS-induced increase in lipid peroxidation and the reduction of glutathione levels in the hippocampus and prefrontal cortex. The present study suggests that atorvastatin treatment exerted neuroprotective effects against LPS-induced depressive-like behaviour which may be related to reduction of TNF-α release, oxidative stress and modulation of BDNF expression.

Are 6-8 year old Italian children moving away from the Mediterranean diet?

BACKGROUND: The Mediterranean diet (MD) is considered one of the healthiest dietary models, as it decreases the risk of chronic diseases and may modulate the organism's early response to environmental pollution. In recent decades, Mediterranean countries have been replacing their traditional diet with other less healthy eating habits, especially among children and teenagers. OBJECTIVE: The aim of this study was to evaluate the MD and the level of adherence to it in 6-8 year old Italian children, in relation to residence, lifestyle, and social and family contexts. METHODS: A questionnaire was administered to the children's parents in two seasons in 5 Italian towns. The diet section contained 116 questions investigating the frequency of consumption of different types of food. The Italian Mediterranean Index (IMI) was calculated according to the intake of 6 typical Mediterranean and 4 non-Mediterranean foods. On the basis of IMI score, MD adherence was classified as low (≤ 3 IMI score), medium (4-5) and high (≥ 6). Total energy load and diet composition in micro- and macronutrients were calculated from consumption frequency. RESULTS: Diet analysis was computed on 1164 subjects with two complete questionnaires. Body mass index, calculated for each subject, showed that 28.9% of the children were overweight, the figure varying slightly with area of residence. Our findings showed that 59.0% of the children had a low score for MD adherence. CONCLUSIONS: The results of this study showed that most Italian children did not follow the MD and socio-economic characteristics appeared not to be associated with type of diet.

Feasibility and reliability of a questionnaire for evaluation of the exposure to indoor and outdoor air pollutants, diet and physical activity in 6-8-year-old children.

INTRODUCTION: The MAPEC-Life project aims to study the biological effects of early exposure to air pollutants on the oral mucosa cells of school-age children in five Italian cities. A questionnaire was created to evaluate the association between outdoor and indoor airborne pollutants, lifestyle, diet and biomarker effects. The feasibility and reliability of the questionnaire were evaluated. METHODS: A questionnaire was drawn up to be filled in by the parents of 6-8-year-old children. It consisted of 148 questions on the children's health, physical activity, environmental exposures and the frequency of food consumption at the main meals. First we conducted a questionnaire feasibility study involving 53 volunteer parents. We then performed a reliability study by administering the questionnaire to a further 156 parents and again one month later (test/retest method). The correlations between answers at the first and second administration of the questionnaire were evaluated using the Kappa statistic and Spearman's coefficient. RESULTS: After verifying the feasibility of the questionnaire, we conducted a reliability analysis on 132 completed questionnaires. The percentage of agreement between the first and the second responses given was over 70%, all K values being greater than 0.6. The analysis of calories and macronutrients also showed good agreement. CONCLUSIONS: The questionnaire drawn up for the study proved to be sufficiently reliable for gathering information about the factors of interest in our study of the relationship between air pollution and early biological effects in children.

Efficacy and safety of antiretrovirals in HIV-infected patients with cancer.

At 30 years into the HIV infection epidemic, the optimal antiretroviral (ARV) regimen for infected patients with cancer remains unknown. We therefore sought to retrospectively study different ARV regimens used in this population. Data from HIV-infected patients seen at The University of Texas MD Anderson Cancer Center in Houston, Texas, USA, from 2001 to 2012 were reviewed. Patients received nucleoside reverse transcriptase inhibitors (NRTIs) plus protease inhibitors (PIs), non-NRTIs (NNRTIs), integrase strand-transfer inhibitors (INSTIs), or combinations of these. A total of 154 patients were studied. Most patients were male (80%), white (51%) and had haematological malignancies (HMs) (58%). NRTIs were combined with PIs (37%), NNRTIs (32%), INSTIs (19%) or combinations of these (11%). INSTIs were the most commonly used in patients with HM and in those receiving high-dose steroids or topoisomerase inhibitors (p <0.05). Side-effects occurred in 35%, 14%, 3% and 6% of patients receiving PIs, NNRTIs, INSTIs and combinations, respectively (p 0.001). Grade 3-4 adverse events were uncommon. Multivariate logistic regression analysis demonstrated that INSTIs and NNRTIs were nine times (95% confidence interval (CI), 1.4-50.8) and 11 times (95% CI, 1.9-64.7) more likely to be effective at 6 months, respectively, than PIs. This is the largest reported analysis studying different ARV regimens in HIV-infected cancer patients. Combinations that included PIs were the least favourable. NNRTIs and INSTIs had comparable efficacy, but INSTIs appeared to be the better tolerated ARVs in patients with HM or those receiving various chemotherapeutic agents.

Pulmonary cryptococcosis in childhood systemic lupus erythematosus and Sjögren syndrome overlap: a rare opportunistic infection.

Meningitis is the main manifestation of cryptococcosis in adult systemic lupus erythematosus (SLE) patients, and other organs and systems, such as the lungs, are rarely affected in this fungal infection. To our knowledge, no case of pulmonary cryptococcosis has been described in the pediatric lupus population. Therefore, we report herein one patient with childhood SLE (C-SLE) and Sjögren's syndrome overlap that presented encapsulated Cryptococcus yeast cells in lung tissue. A 14-year-old girl was diagnosed with C-SLE. At the age of 16 years and 5 months, she presented with fever, cough and dyspnea, without headache, vomiting, and also without signs of meningeal irritation or other clinical manifestations. She was being treated with mycophenolate mofetil, hydroxychloroquine and prednisone. Chest radiography and chest computer tomography showed a single nodule in the left posterior apex and three nodular lesions in the left hemithorax respectively. Bronchoalveolar lavage and transbronchial biopsy were normal and without isolation of bacteria or fungi. Voriconazole was empirically introduced for 21 days. Fifteen days after the first biopsy, she underwent open thoracotomy with surgical left lung biopsy and was diagnosed with pulmonary cryptococcosis. Voriconazole was replaced with oral fluconazole and this antifungal therapy was maintained with improvement of clinical manifestations and without marked alteration of radiological images. In conclusion, we report the first case of pulmonary cryptococcosis in Sjögren's and C-SLE patient with a satisfactory clinical response to antifungal therapy. Fungal infections should be excluded in the presence of lung nodules and etiological identification is required for proper treatment.

Efficacy of food supplement to improve metabolic syndrome parameters in patients affected by moderate to severe psoriasis during anti-TNFα treatment.

AIM: Psoriasis is a systemic inflammatory immune-mediated skin disease. Recently a relationship with metabolic syndrome in terms of psoriasis severity and response to therapy was observed. METHODS: We performed an open-label randomized controlled study to evaluate the role of a nutraceutical containing Q10 coenzyme, Krill-oil, lipoic acid, resveratrol, Vitis vinifera seed oil, vitamin E and selenium in addition to etanercept therapy for patients affected by psoriasis and metabolic syndrome. Forty patients were enrolled and divided into two arms, one receiving only etanercept, one other receiving also the neutraceutical. After a period of 3 months (T1) a second evaluation of the considered parameters was performed. RESULTS: At T1 statistically significant differences were detected in HDL cholesterol and triglycerides values both comparing the two arms and in the nutraceutical arm. CONCLUSION: Our results show that the dietary addiction of the nutraceutical to the etanercept therapy in patients affected by both psoriasis and metabolic syndrome could help to restore the normal lipid profile.

AMPK inhibition enhances apoptosis in MLL-rearranged pediatric B-acute lymphoblastic leukemia cells.

The serine/threonine kinase AMP-activated protein kinase (AMPK) and its downstream effectors, including endothelial nitric oxide synthase and BCL-2, are hyperactivated in B-cell precursor-acute lymphoblastic leukemia (BCP-ALL) cells with MLL gene rearrangements. We investigated the role of activated AMPK in supporting leukemic cell survival and evaluated AMPK as a potential drug target. Exposure of leukemic cells to the commercial AMPK inhibitor compound C resulted in massive apoptosis only in cells with MLL gene rearrangements. These results were confirmed by targeting AMPK with specific short hairpin RNAs. Compound C-induced apoptosis was associated with mitochondrial membrane depolarization, reactive oxygen species production, cytochrome c release and caspases cleavage, indicating intrinsic apoptosis pathway activation. Treatment with low concentrations of compound C resulted in a strong antileukemic activity, together with cytochrome c release and cleavage of caspases and poly(ADP-ribose) polymerase, also in MLL-rearranged primary BCP-ALL samples. Moreover, AMPK inhibition in MLL-rearranged cell lines synergistically enhanced the antiproliferative effects of vincristine, daunorubicin, cytarabine, dexamethasone and L-asparaginase in most of the evaluated conditions. Taken together, these results indicate that the activation of the AMPK pathway directly contributes to the survival of MLL-rearranged BCP-ALL cells and AMPK inhibitors could represent a new therapeutic strategy for this high-risk leukemia.

Recent advances in the adjuvant treatment of early breast cancer.

The majority of breast cancers are actually diagnosed at an early stage. Selection of the best treatment in the adjuvant setting represents a paramount step to reduce the risk of recurrence and cancer-specific mortality. At the present time decision making is based on individualized risk assessment, that takes into account patient and tumor clinical-pathological characteristics. New available tools, such as gene expression profiling, offer the potential to provide accurate prognostic and predictive information, but they require further validation. The present article provides an overview of current strategies in adjuvant breast cancer setting, and addresses a number of unresolved questions related to the role of taxanes, trastuzumab and hormonal treatment.

[Adjuvant chemotherapy in hormone-receptor positive HER2-negative early breast cancer]. / Chemioterapia adiuvante del carcinoma della mammella con recettori ormonali positivi HER2-negativo.

Adjuvant treatment in hormone-receptor positive, HER2-negative early breast cancer is controversial. Chemotherapy benefit in this subset of patients is generally small, and a wide variability exists among dif-ferent subgroups of patients, depending on various patient and tumor characteristics. To select subsets of patients who will really benefit from chemotherapy, one of the possible strategy is based on multigene expression analysis. This approach is providing deeper insights into the biological heterogeneity of breast cancer, allowing to further sub-divide hormone-receptor positive tumors into groups, with different clinical behavior and response to treatments. Among less expensive and better validated methods, high levels of Ki67, a routinely assessed immunohistochemical marker of cell proliferation, can suggest the use of chemotherapy in this subset of patients. Generally, regimen used should include a taxane. In fact, retrospective analyses of clinical trials suggest that anthracyclines may be less active in hormone-receptor positive HER2-negative patients, while several other trials and meta-analyses involving taxanes, showed a benefit in terms of risk of relapse and death reduction. Among taxanes, docetaxel should be preferred because of a better therapeutic index, and a higher activity in comparison to paclitaxel. At present, reliable and accurate evaluation of histopathological and immunohistochemical factors may allow the choice of omitting adjuvant chemotherapy in patients with low risk hormone receptor positive HER2-negative breast cancer. Uncertainty still exists about chemotherapy benefit for a substantial proportion of women of this subgroup. Nevertheless, the addition of taxanes, mainly docetaxel, to anthracyclines, seems to overcome the relative chemoresistance of hormone-receptor positive tumors, providing a benefit in disease free survival and overall survival.

[Role of adjuvant chemotherapy in the choice of chemotherapeutic treatment of metastatic breast cancer]. / Ruolo della chemioterapia adiuvante nella scelta del trattamento chemioterapico del carcinoma mammario metastatic

Adjuvant treatment of early breast cancer has changed considerably in recent years, and the majority of patients are currently treated with the most active single agents in this setting. As a result, the decisions regarding the treatment of patients with metastatic breast cancer have become more difficult. In patients who have not received chemotherapy for early-stage breast cancer or were treated with CMF, many choices are available, including regimens containing anthracyclines or taxanes. Patients who received anthracyclines in the adjuvant setting, may sometimes be re-treated with these agents, and the inclusion of a taxane is frequently the most reasonable choice. Among taxanes, docetaxel should be preferred because it is the most active single agent, and has a synergistic action with several other drugs, when used in combination. Taxanes can be used also in selected patients who had received these agents as adjuvant treatment. In particular, docetaxel did not show complete cross-resistance with paclitaxel, whereas weekly paclitaxel is only minimally effective in patients resistant to docetaxel. Retreatment with trastuzumab combined with chemotherapeutic agents might be a reasonable option in patients who had received adjuvant chemotherapy with trastuzumab. Nevertheless, another recent option is the combination of chemotherapy with lapatinib. Currently, novel target agents are being developed, with the potential to improve survival in patients with metastatic breast cancer. Arguably, the future for treatment of these patients appears to be the combination of effective single agents, such as docetaxel, with novel biologic therapies.

Docetaxel in the adjuvant therapy of HER-2 positive breast cancer patients.

Considering the clinical benefit of trastuzumab in advanced breast cancer, fi ve prospective adjuvant randomized trials have recently been completed and early results have been published. Two of them, (NSABP-B31 and NCCTG N9831), employed anthracycline-containing regimens with sequential paclitaxel, with or without trastuzumab. The third study, HERA trial, randomized patients after adjuvant chemotherapy into an observational arm, one or two years of trastuzumab. Results of these studies, after a median follow up of 2-3 years confirm a DFS and OS benefit for the experimental arms. The worst rate of cardiotoxicity, in terms of incidence of CHF, with the use of trastuzumab and anthracycline based regimens was 4.1% in the trastuzumab arm of the NSABP-B31 trial. Among the fi ve trastuzumab trials, two, BCIRG 006 and FinHer, employed docetaxel-based regimens. The innovative BCIRG 006 trial compared ACdocetaxel (T) with two trastuzumab-containing regimens, ACTH, and a non-anthracycline-containing regimens, TCH, with a clear advantage in DFS for both trastuzumab arms. Data from the second interim analysis indicate that, in the subgroup of patients without co-amplification of topoisomerase 2 (TOPO-2), the arm without trastuzumab (ACT) showed a DFS significantly poorer that in the other arms; moreover, if we consider the lower toxicity of TCH regimen in comparison with anthracycline-containing arms, the innovative statements offered by BCIRG 006 trial appear evident, and these findings opened an important question about the consolidated employment of anthracyclines in adjuvant setting.The FinHer trial was a small trial testing a short course of trastuzumab (9 weeks) concomitantly with a chemotherapy including docetaxel, and there was a significant advantage in DFS for the trastuzumab based arms, without relevant toxicity and without any cardiotoxicity. Although data from all trastuzumab adjuvant trials, and without particulary from BCIRG-006 and FinHer trials, appear very intriguing, further follow-up is required.

Optimal sequence of anthracyclines and taxanes as adjuvant breast cancer treatment.

Results from randomized trials evaluating taxane versus non-taxane containing regimens in adjuvant breast cancer treatment indicate an advantage in DFS and OS for the taxane-arms, but the best schedule of administration, in combination with anthracyclines or in sequence, is still a debated issue, even if the sequential strategy appears to be less toxic. Up to now, the majority of clinical trials employed the "standard" sequence, with anthracycline-based combinations fi rst, followed by taxanes. Few small phase II trials evaluated the reverse sequence, with taxanes administered fi rst, most of them in metastatic or neoadjuvant setting, suggesting efficacy and lower toxicity. An important issue to be considered is the hypothesized differences in the ability of the drugs to induce cross-resistance to each other, as suggested by data of a preclinical study, and from clinical study with a cross-over design; results of these trials suggest that the best strategy would be to administer a taxane prior to an anthracycline, also according to the Norton and Simon hypothesis. Moreover, trials evaluating the best sequence of anthracyclines and taxanes in adjuvant breast cancer setting are of small sample size, and an adequately powered randomized phase III trial is needed before definitive conclusions are reached.

[Neoadjuvant endocrine therapy for locally advanced breast cancer]. / L'ormonoterapia nel trattamento neoadiuvante del carcinoma mammario localmente avanzato.

The use of neoadjuvant chemotherapy in the treatment of locally advanced breast cancer is now well established. However, endocrine therapy can be a valid alternative to primary chemotherapy in the treatment of hormone-sensitive tumors, particularly in post-menopausal women. Tamoxifen (TAM) was initially used in older or frail patients who were not candidates for chemotherapy. Response rate of 49% to 68% were observed. These encouraging results prompted subsequent randomized phase III studies demonstrating the superiority of surgery in comparison to TAM as primary treatment. The successful use of aromatase inhibitors (AI) in the metastatic and adjuvant setting has encouraged studies that compare these agents with tamoxifen in the neoadjuvant setting. In terms of response rates, anastrozole and exemestane did not differ from TAM, while letrozole was superior. Nevertheless, all the AI were found to be superior to TAM as far as breast conserving surgery is concerned. The Americal College of Surgeons Oncology Group (ACOSOG) has recently activated a neoadjuvant randomized trial comparing anastrozole, letrozole and exemestane in postmenopausal patients with estrogen receptor positive tumors. Hopefully, this study will clarify which of these agents is more effective as primary endocrine therapy. In the meantime, neoadjuvant hormonal treatment should be considered in elderly patients with inoperable tumors or tumors not amenable to conservative surgery, with highly expressed estrogen receptors and contraindication to chemotherapy.

[High-dose CEF (cyclophosphamide, epirubicin, fluorouracil) as primary chemotherapy in locally advanced breast cancer: long-term results]. / CEF (ciclofosfamide, epirubicina, fluorouracile) ad alte dosi come chemioterapia primaria nel trattamento del carcinoma mammario localmente avanzato: risultati a lungo termine.

PURPOSE: To determine wether primary CEF is effective in locally advanced breast cancer, as measured by response, local recurrences, disease free survival (DFS) and overall survival (OS). MATERIAL AND METHODS: From 1990 to 1998, 62 patients with stage III disease were enrolled into a prospective study at Regina Elena Institute for Cancer Research, Rome. Inflammatory breast cancer (IBC) was included. Patients received three 21 days cycles of chemotherapy that consisted in epirubicin 50 mg/m2, cyclophosphamide 400 mg/m2, and fluorouracil 500 mg/m2 i.v. on days 1 and 8. G-CSF (300 microg) was given subcutaneously every other day from day 5 to day 17. After primary chemotherapy, whenever possible, mastectomy or conservative surgery was performed. Subsequently responding patients received the same regimen, while non responders were given a non cross resistant chemotherapy. In case of conservative surgery or initial T4 tumor radiation therapy was performed at the end of adjuvant chemotherapy. ER positive patients received tamoxifen 20 mg/d for five years. RESULTS: Seven IIIA patients had a median OS of 43 months (C.I. 95%, 31-55) and DFS of 42 months (C.I. 95%, 16-68), while 15 IBC patients had a median OS of 52 months (C.I. 95%, 52-79) and DFS of 27 months (C.I. 95%, 14-39). Forty IIIB non inflammatory breast cancer patients had a median DFS of 87 months (C.I. 95%, 1-175); median OS was not reached. Ten-year OS was 28.6% for stage IIIA, 50.6% for stage IIIB and 36% for IBC. CONCLUSION: Primary CEF appear to be an effective treatment. In our study we obtained a good local control and interesting long term data of disease free and overall survival.

Smoking, polyuria and impaired vision.

The pituitary gland can be involved in a variety of medical conditions, including metastatic tumors. Metastases to the pituitary gland, although absolutely rare, more commonly affect the posterior pituitary lobe and so frequently present with diabetes insipidus. We report on a 48-year-old male heavy smoker patient suffering from sudden onset of polyuria and persistent thirst. Laboratory results revealed central diabetes insipidus. Computed tomography (CT) scan of the brain showed a mass located in the sella turcica and in the suprasellar region. CT scan of the chest showed a mass in the right superior lobe with mediastinal lymphadenopathy, with bronchoscopy and biopsy features of pulmonary adenocarcinoma. The patient received radiotherapy on the pituitary gland and adjuvant chemotherapy, and as intrasellar and suprasellar mass decreased in size, urinary output was accordingly reduced. Therefore, is that in patients with risk factors for cancer and sudden onset of diabetes insipidus pituitary metastasis should be taken into account in differential diagnosis.

Induction of apoptosis in Jurkat cells by photoexcited psoralen derivatives: Implication of mitochondrial dysfunctions and caspases activation.

The prevailing form of cell death in lymphocytes exposed to psoralen plus UVA light (PUVA), was investigated. We studied the well known drug 8-methoxypsoralen (8-MOP) and an angular derivatives: angelicin (ANG). We evaluated the induction of apoptosis in a human tumor T-cell line (Jurkat). Both compounds provoke a significant induction of apoptosis at 24h from irradiation as demonstrated by a remarkable percentage of cells Annexin-V positive. We investigated the effects of the psoralen derivatives upon UVA irradiation on the cell cycle. The flow cytometric analysis of propidium labeled cells indicates that treatment induces, in a dose dependent manner, a massive accumulation of cells, for both compounds, in G2-S phase after 24h from the irradiation. We have focused our attention on the mitochondrial functionality after irradiation in the presence of psoralen derivatives. We evaluated, by flow cytometry, (i) the mitochondrial potential (Deltapsi(mt)), (ii) the production of reactive oxygen species (ROS) and (iii) the oxidation of cardiolipin, a phospholipid restricted to the inner mitochondrial membrane. Furthermore the activation of caspases -3, -8 and -9 was also investigated. The obtained data indicated that, upon UVA irradiation, the two compounds induce a strong decrease in mitochondrial functions and activate caspase-3, -8 and -9.