The role of the Community Pharmacist in promoting vaccinations among general population according to the National Vaccination Plan 2017-2019: results from a survey in Sicily, Italy.

INTRODUCTION: The 2017-2019 Italian National Vaccination Plan promotes the improvement of knowledge and attitudes of healthcare workers about vaccine prevention, in order to spread a vaccination culture among general population. Similarly to the General Practitioner, the Pharmacist represents a fundamental forefront for both patients and healthy people, also in promoting vaccine acceptance. This research aims to analyze knowledge and attitudes about vaccines of Community Pharmacists and to evaluate the burden of vaccination counselling during their work activities. MATERIAL AND METHODS: A standardized, self-administered and previously validated questionnaire, including 5 sections and 28 items, was submitted to a sample of Community Pharmacists working in Western Sicily. The survey was carried out through an online questionnaire, that investigated socio-demographic data, knowledge and attitudes towards vaccination and the role of the Pharmacist as vaccination counselor during his work. RESULTS: A total of 120 Pharmacists were surveyed. 99.2% of them were definitely agreed with the Regional Vaccination Schedule. A large majority (n = 114, or 95%) were fully vaccinated and have vaccinated, or would vaccinate in future, their children. According to Community Pharmacists interviewed, at least 90% of clients asked for further explanations about vaccination, and the citizens' trust towards vaccination increased (30%) or remained stable (54.2%) over time in the last 5 years. Finally, as reported by interviewed Pharmacists, a correct counselling provided by General Practitioners (GPs) and Family Pediatricians was the main boost in increasing vaccination confidence, instead of mass-media and web misinformation that has led to skepticisms among general population. CONCLUSION: The study demonstrated the key role of the Community Pharmacist for their consumers in vaccination counselling. In future, a strong collaboration between Community Pharmacists and all the actors promoting vaccination themes (GPs, family Pediatricians, public health workers) will be essential, as well as a uniform and standardized University training on vaccination themes for all these categories.

Serum sickness (Like Reaction) in a patient treated with alemtuzumab for multiple sclerosis: A case report.

BACKGROUND: Alemtuzumab is a monoclonal antibody approved for relapsing-remitting multiple sclerosis (RRMS). The only report of Serum Sickness (SS) in a MS patient occurred during treatment with natalizumab. Non-protein drugs, such as some antibiotics, may induce "SS-like" reactions (SSLR), whose clinical and laboratory features may partially overlap with the traditional SS. OBJECTIVE: To report a case of SS/SSLR in a RRMS patient treated with alemtuzumab. CASE REPORT: A 42-year-old-woman with RRMS developed SS/SSLR in the first week after the first alemtuzumab treatment. Concomitant medications included trimethoprim-sulfamethoxazole at low dose. Intravenous methylprednisolone therapy led to clinical resolution and normalization of serum inflammatory markers. CONCLUSION: SS/SSLR should be considered in patients treated with alemtuzumab developing delayed fever, rash and arthralgia and differentiated with Infusion Associated Reactions (IARs) and infections.

The Socio-Economic Health Deprivation Index and its association with mortality and attitudes towards influenza vaccination among the elderly in Palermo, Sicily.

INTRODUCTION: Socio-economic status (SES) seems to be a determinant of health and is associated with vaccination coverage among older and at-risk populations. The aim of this study was to evaluate trends in health outcomes and the Socio-Economic and Health Deprivation Index (SEHDI) among elderly people in the city of Palermo. METHODS: In the 2015 CCM project, the Palermo Unit collected mortality data for use in validating the SEHDI. Italian census data from 2009 to 2015 on overall mortality and causes of death were used. The outcome used to validate the SEHDI was vaccination coverage from the 2009-2010 to 2014-2015 influenza seasons among the elderly in Palermo. RESULTS: The SEHDI correlated significantly with all-cause mortality (p < 0.05), though this correlation displayed a decreasing trend. Regarding mortality due to influenza or pneumonia, however, the significant correlation (p < 0.05) showed an increasing trend. A linear trend was observed in the inverse correlation between the SEHDI and vaccination coverage rates (p < 0.05), with an overall 27% vaccination coverage among older people. Elderly subjects living in a census district with more regular immigrants, divorced people and single-parent families were more reluctant to undergo influenza vaccination. CONCLUSIONS: This study allowed us to identify subgroups of elderly people who are less likely to adhere to influenza vaccination, and to whom health promotion interventions could be addressed in order to facilitate "healthy aging".

Peripheral neuropathy in late-onset Krabbe disease: report of three cases.

Late-onset Krabbe disease may have variable misleading clinical manifestations and be a puzzling problem for physicians. We report clinical and peripheral nerve studies of three patients with adult-onset Krabbe disease. Two cases had a predominantly spastic paraparesis; in one case, the symptoms mimicked a cerebrovascular disorder. Predominantly, demyelinating neuropathy was observed in one case and axonal neuropathy in two cases. In all cases, no typical intracytoplasmic inclusions were found. These observations suggest that peripheral neuropathy in adult-onset Krabbe disease has variable clinical and pathological characteristics, different from those described in the classic form.

Unknown primary tumors.

An unknown primary tumor (UPT) is defined by the presence of a metastatic cancer without a known primary site of origin despite a standardized diagnostic workup. Clinically, UPTs show rapid progression and early dissemination, with signs and symptoms related to the metastatic site. The molecular bases of their biology remain largely unknown, with no evidence as to whether they represent a distinct biological entity. Immunohistochemistry remain the best diagnostic tool in term of cost-effectiveness, but the time-consuming "algorithmic process" it relies on has led to the application of new molecular techniques for the identification of the primary site of UPTs. For example, several microarray or miRNA classifications of UPTs have been used, with an accuracy in the prediction of the primary site as high as 90%. It should be noted that validating a prediction of tissue origin is challenging in these patients, since most of them will never have a primary site identified. Moreover, prospective studies to determine whether selection of treatment options based on such profiling methods actually improves patient outcome are still missing. In the last few years functional imaging (i.e. FDG-PET/CT) has gained a main role in the detection of the site of origin of UPTs and is currently recommended by the European Association of Nuclear Medicine. However, despite recent refinements in the diagnostic workup, the site of origin of UPT often remains elusive. As a consequence, treatment of patients with UPT is still empirical and inadequate.

Investigator-initiated trials of targeted oncology agents: why independent research is at risk?

BACKGROUND: Drug development traditionally has relied upon the complementary contributions of clinicians and scientists at academic institutions and at pharmaceutical companies. Greater regulatory burdens, increased bureaucratic requirements, restricted reimbursement, and spiralling research and development costs are exerting pressure on the drug development pipeline. The result is a de-emphasis of exploratory research, particularly independent academic research, despite its proven value in identifying new drug targets and developing innovative cancer therapies. DESIGN: An expert panel assembled by the Biotherapy Development Association-a nonprofit international forum for academic and industry researchers, patients, and government regulatory and postregulatory agencies-examined the growing schism between academia and industry and identified several causes of declining academic research. RESULTS: The authors propose solutions to sustain investigator-initiated research and provide a new model whereby expert organisations provide a forum for academia and industry to plan studies within a regulatory framework to support licensure/authorisation and reimbursement for new molecularly targeted agents and biomarkers. CONCLUSIONS: Investigator-initiated trials have led to the discovery and development of innovative, safe, and effective cancer treatments. To ensure that such research continues, action will be required on the parts of legislative and regulatory bodies, industry, universities, patient advocacy organisations, and preclinical and clinical academic scientists.

Increased lung surfactant phosphatidylcholine in patients affected by lysosomal storage diseases.

Sandhoff disease, Gaucher disease type I and sialidosis type I are lysosomal storage disorders caused, respectively, by deficiency of activity of beta-hexosaminidase (storage of GM(2) and GA(2) ganglioside), glucosylceramidase (storage of glucosylceramide) and alpha-neuraminidase (storage of glucopeptides and/or oligosaccharides). Progressive clinical systemic and neurological dysfunctions are observed. In these pathologies, respiratory infections often lead to death. Elevation of the lung surfactant phosphatidylcholine (PC) has previously been reported in the Hexb mouse, a model of Sandhoff disease. We evaluated phospholipids in the lung surfactant of patients affected by the described lysosomal diseases, observing a statistically significant increase of total lipid phosphate in the patients as compared with controls. Moreover, higher levels of PC in patients affected by sialidosis (3.6-fold) and Gaucher (4-fold) disease, and of PC (4.15-fold) and phosphatidylethanolamine (2.3-fold) in a patient affected by Sandhoff disease were noted. The latter confirms the previous results in the Hexb mouse. We suggest that changes in phospholipid metabolism can be common in different lysosomal storage disorders and can increase the susceptibility to respiratory infections, usually present in these disorders.

Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101).

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles. RESULTS: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens. CONCLUSIONS: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.

Leukoencephalopathy as a rare complication of hepatitis C infection.

We report the case of a 64-year-old female patient with hepatitis C infection (HCV), who developed Sjögren's disease and sensory peripheral neuropathy. Clinical conditions worsened over three years with central nervous system involvement characterised by transient third cranial nerve paresis and mild selective impairment of attention and memory. Brain magnetic resonance imaging showed diffuse periventricular and lobar white matter hyperintensity. Laboratory findings included mixed cryoglobulinaemia (type II), cryocrit 1.47%, low serum levels of complement C4 and high levels of rheumatoid factor, HCV 1b genotype, high HCV mRNA levels in serum and cerebrospinal fluid. Skin biopsy showed evidence of vasculitis. After one year of plasmapheresis, immunosuppressant therapy and occasional corticosteroid treatment, neurological symptoms improved, skin biopsy changed and inflammation parameters normalised, suggesting that neurological symptoms might be related to the high levels of mixed cryoglobulins.

Periventricular heterotopia: phenotypic heterogeneity and correlation with Filamin A mutations.

Periventricular heterotopia (PH) occurs when collections of neurons lay along the lateral ventricles or just beneath. Human Filamin A gene (FLNA) mutations are associated with classical X-linked bilateral periventricular nodular heterotopia (PNH), featuring contiguous heterotopic nodules, mega cisterna magna, cardiovascular malformations and epilepsy. FLNA encodes an F-actin-binding cytoplasmic phosphoprotein and is involved in early brain neurogenesis and neuronal migration. A rare, recessive form of bilateral PNH with microcephaly and severe delay is associated with mutations of the ADP-ribosylation factor guanine nucleotide-exchange factor-2 (ARFGEF2) gene, required for vesicle and membrane trafficking from the trans-Golgi. However, PH is a heterogeneous disorder. We studied clinical and brain MRI of 182 patients with PH and, based on its anatomic distribution and associated birth defects, identified 15 subtypes. Classical bilateral PNH represented the largest group (98 patients: 54%). The 14 additional phenotypes (84 patients: 46%) included PNH with Ehlers-Danlos syndrome (EDS), temporo-occipital PNH with hippocampal malformation and cerebellar hypoplasia, PNH with fronto-perisylvian or temporo-occipital polymicrogyria, posterior PNH with hydrocephalus, PNH with microcephaly, PNH with frontonasal dysplasia, PNH with limb abnormalities, PNH with fragile-X syndrome, PNH with ambiguous genitalia, micronodular PH, unilateral PNH, laminar ribbon-like and linear PH. We performed mutation analysis of FLNA in 120 patients, of whom 72 (60%) had classical bilateral PNH and 48 (40%) other PH phenotypes, and identified 25 mutations in 40 individuals. Sixteen mutations had not been reported previously. Mutations were found in 35 patients with classical bilateral PNH, in three with PNH with EDS and in two with unilateral PNH. Twenty one mutations were nonsense and frame-shift and four missense. The high prevalence of mutations causing protein truncations confirms that loss of function is the major cause of the disorder. FLNA mutations were found in 100% of familial cases with X-linked PNH (10 families: 8 with classical bilateral PNH, 1 with EDS and 1 with unilateral PH) and in 26% of sporadic patients with classical bilateral PNH. Overall, mutations occurred in 49% of individuals with classical bilateral PNH irrespective of their being familial or sporadic. However, the chances of finding a mutation were exceedingly gender biased with 93% of mutations occurring in females and 7% in males. The probability of finding FLNA mutations in other phenotypes was 4% but was limited to the minor variants of PNH with EDS and unilateral PNH. Statistical analysis considering all 42 mutations described so far identifies a hotspot region for PNH in the actin-binding domain (P < 0.05).

Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study.

The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73-1.09) for patients receiving FA and 0.99 (95% CI 0.80-1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80-1.30) and 0.94 (95% CI 0.73-1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients.

Lung involvement in Niemann-Pick disease type C1: improvement with bronchoalveolar lavage.

Progressive lung infiltration is a major cause of death in Niemann-Pick disease type A and B (NPA, NPB) and in the recently defined type C2. In type C1 (NPC1), the main manifestations are neurological. We report a patient with a classic, neurological, late infantile form of NPC1 disease, carrying the mutation P474L and the variant I642M in the NPC1 gene, who suffered recurrent respiratory manifestations. Bronchoalveolar lavage of a lung segment due to deteriorating respiratory condition revealed many foamy macrophages and was followed by an improvement in symptoms. Pneumopathy may therefore be considered a feature of NPC1 disease for which a partial bronchoalveolar lavage could be a useful treatment.

Weekly docetaxel and gemcitabine as first-line treatment for metastatic breast cancer: results of a multicenter phase II study.

OBJECTIVES: We conducted a multicenter phase II study to evaluate the clinical efficacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as first-line treatment of metastatic breast cancer patients. METHODS: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m2 and gemcitabine 800 mg/m2 i.v. on days 1, 8, 15 every 28 days. RESULTS: All patients were assessable for toxicity and 56 for efficacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53-28.67) and median time to tumor progression was 13.6 months (95% CI: 10.71-16.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3-4 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. CONCLUSION: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule, in agreement with other published studies, need to be further confirmed within a phase III study.

Biweekly oxaliplatin combined with oral capecitabine (OXXEL regimen) as first-line treatment of metastatic colorectal cancer patients: a Southern Italy Cooperative Oncology Group phase II study.

Oxaliplatin 100 mg/m(2) iv on day 1, and capecitabine 1,000 mg/m(2) orally bid from day 1 (evening) to day 11 (morning) were administered every 2 weeks (OXXEL regimen) to 38 patients as first-line treatment for metastatic colorectal carcinoma. A total of 318 cycles were administered, with a median of 8 (range, 4-12) cycles per patient. Response rate (RR) was 45% (95% confidence interval (CI), 29%-62%), with 7 complete responses and 10 partial responses; furthermore, 12 patients showed a stable disease, so that a disease control was achieved in 29 (76%) patients. RR was greater among patients with performance status 0 (52%), without weight loss (52%), younger than 65 years (50%), and previously unexposed to adjuvant chemotherapy (48%), while no correlation was found with the actually delivered oxaliplatin dose intensity. Overall, haematological side effects were negligible, with no case of grade 4 toxicity, and only one patient suffering from an episode of grade 3 neutropenic fever. Severe anaemia occurred in 4 (11%) patients, and grade 3 neuropathy affected 9 (24%) patients. Median progression-free survival was 7.9 (95% CI, 6.2-9.6) months, and median overall survival has not been reached yet. In conclusion, the OXXEL regimen resulted safe and active, and it deserves further evaluation in metastatic colorectal cancer patients.

Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial.

PURPOSE: The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma. PATIENTS AND METHODS: Patients with measurable metastatic colorectal carcinoma were randomly allocated to receive: IRI 200 mg/m(2) on day 1, l-FA 250 mg/m(2) intravenously plus 5-FU 850 mg/m(2) on day 2 (IRIFAFU); or OXA 100 mg/m(2) on day 1, l-FA 250 mg/m(2) plus 5-FU 1050 mg/m(2) on day 2 [OXAFAFU high dose (hd)]. Cycles were given every 2 weeks. After a planned interim analysis, OXA was reduced to 85 mg/m(2) and 5-FU to 850 mg/m(2) [OXAFAFU low dose (ld)]. RESULTS: Two hundred and seventy-four patients (IRIFAFU, 135; OXAFAFUhd, 71; OXAFAFUld, 68) were treated. Forty-two confirmed responses were achieved with IRIFAFU, 29 with OXAFAFUhd and 32 with OXAFAFUld. The response rate with OXAFAFU [44%; 95% confidence interval (CI) 35% to 52%] was significantly higher (P=0.029) than that of IRIFAFU (31%; 95% CI 23% to 40%). Occurrence of grade > or =3 neutropenia with OXAFAFUld was similar to that for IRIFAFU (29% versus 31%), while severe diarrhoea was significantly lower (12% versus 24%). Median failure-free survival (7 versus 5.8 months; P=0.046) and overall survival of patients (18.9 versus 15.6 months; P=0.032) were significantly prolonged with OXAFAFU. CONCLUSIONS: OXAFAFU was more active and less toxic than IRIFAFU, and it should be preferred in the first-line treatment of advanced colorectal cancer patients.

Randomised, open-label, phase II trial of paclitaxel, gemcitabine and cisplatin versus gemcitabine and cisplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium.

The purpose of the study was to evaluate the antitumor activity and the safety of paclitaxel combined with gemcitabine and cisplatin in patients affected by advanced transitional cell carcinoma of the urothelium (TCC). Eighty-five patients affected by advanced TCC and measurable disease were randomized to receive either paclitaxel at dosage of 70 mg/m2, gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks (GCP) or gemcitabine 1000 mg/m2 on days 1, 8, 15 and cisplatin 70 mg/m2 on day 2 every 4 weeks (GC). All enrolled patients were considered evaluable for response and toxicity (intention to treat). The observed response rate was 43% for GCP and 44% for GC combination, respectively. Median time to treatment failure was 32 weeks for GCP and 26 weeks for GC and overall survival 61 vs 49 weeks, respectively (p-value not significant). Grade 3-4 neutropenia was observed in 49% of patients treated with GCP vs 35% of those treated with GC (P=0.05) and grade 3-4 thrombocytopenia was observed in 36% of GCP treated patients as compared to 21% of those treated with GC (P=0.01). Seven patients over 70 years old or with poor PS were removed from the study: 6 patients from GCP group (2 toxic deaths, 2 grade 4 myelotoxicity and 2 grade 3 asthenia) and 1 from GC group was lost to follow-up after the first cycle. The combination of paclitaxel, gemcitabine and cisplatin is effective in the treatment of TCC. However, the addition of paclitaxel to the combination of gemcitabine plus cisplatin seems to increase toxicity, therefore it seems not suitable for poor PS patients and those over 70 years old. Larger and more powered studies are needed to exactly define the role of paclitaxel in this combination.

A randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer.

The sequential doxorubicin --> CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF x 6 cycles (CMF); (b) doxorubicin x 4 cycles followed by CMF x 6 cycles (A --> CMF); (c) CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (CMF --> GT); and (d) doxorubicin x 4 cycles followed by CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (A --> CMF --> GT). The study used a 2 x 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A --> CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A --> CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556-0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555-0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54-1.32). A --> CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients.

Novel SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay type.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset familial disease with prominent myelinated fibers in the optic fundus. ARSACS is frequent in the Charlevoix-Saguenay region of Quebec but rare elsewhere. Mutations in SACS, encoding sacsin, a protein of unknown function, are associated with ARSACS. The authors identified three new SACS mutations in two Italian patients whose phenotype closely matches that of Quebec cases, but without retinal striation.