Antisepsis of the skin before spinal surgery with povidone iodine-alcohol followed by chlorhexidine gluconate-alcohol versus povidone iodine-alcohol applied twice for the prevention of contamination of the wound by bacteria: a randomised controlled trial.

AIMS: The aim of this study was to determine whether the sequential application of povidone iodine-alcohol (PVI) followed by chlorhexidine gluconate-alcohol (CHG) would reduce surgical wound contamination to a greater extent than PVI applied twice in patients undergoing spinal surgery. PATIENTS AND METHODS: A single-centre, interventional, two arm, parallel group randomised controlled trial was undertaken, involving 407 patients who underwent elective spinal surgery. For 203 patients, the skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice, and for 204 patients using PVI once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). The primary outcome measure was contamination of the wound determined by aerobic and anaerobic bacterial growth from samples taken after disinfection. RESULTS: The detection of viable bacteria in any one of the samples taken after disinfection (culture-positive) was significantly lower in the group treated with both PVI and CHG than in the group treated with PVI alone (59 (29.1%) versus 85 (41.7%), p = 0.009; odds ratio 0.574; 95% confidence interval, 0.380 to 0.866). CONCLUSIONS: Antisepsis of the skin with the sequential application of PVI and CHG more effectively reduces the contamination of a surgical wound than PVI alone. Cite this article: Bone Joint J 2017;99-B:1354-65.

Preventive treatments for breast cancer: recent developments

Breast cancer is a burden for western societies, and an increasing one in emerging economies, because of its high incidence and enormous psychological, social, sanitary and economic costs. However, breast cancer is a preventable disease in a significant proportion. Recent developments in the armamentarium of effective drugs for breast cancer prevention (namely exemestane and anastrozole), the new recommendation from the National Institute for Health and Care Excellence to use preventative drugs in women at high risk as well as updated Guidelines from the US Preventive Services Task Force and the American Society of Clinical Oncology should give renewed momentum to the pharmacological prevention of breast cancer. In this article we review recent major developments in the field and examine their ongoing repercussion for breast cancer prevention. As a practical example, the potential impact of preventive measures in Spain is evaluated and a course of practical actions is delineated (AU)

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Preventive treatments for breast cancer: recent developments.

Breast cancer is a burden for western societies, and an increasing one in emerging economies, because of its high incidence and enormous psychological, social, sanitary and economic costs. However, breast cancer is a preventable disease in a significant proportion. Recent developments in the armamentarium of effective drugs for breast cancer prevention (namely exemestane and anastrozole), the new recommendation from the National Institute for Health and Care Excellence to use preventative drugs in women at high risk as well as updated Guidelines from the US Preventive Services Task Force and the American Society of Clinical Oncology should give renewed momentum to the pharmacological prevention of breast cancer. In this article we review recent major developments in the field and examine their ongoing repercussion for breast cancer prevention. As a practical example, the potential impact of preventive measures in Spain is evaluated and a course of practical actions is delineated.

An uncommon association of antiphospholipid syndrome, selective IgA deficiency and resistant-to-treatment relapsing polychondritis: efficacy of infliximab.

Autoimmune complications in the context of primary immunodeficiency diseases represent a well-known phenomenon, and this is widely recognized also for Selective Immunoglobulin A deficiency (IgAD), the most common primary antibody deficiency (PAD). Relapsing polychondritis (RP) is a rare immune-mediated, difficult to treat, disorder in which the cartilaginous tissues are the target for inflammation and damage. Ocular inflammatory manifestations in RP are frequent and often sight-threatening. Antiphospholipid syndrome (APS) is an acquired prothrombotic state related to circulating autoantibodies against phospholipids and/or their cofactors. Rare reports of APS associated to RP, PAD and APS or PAD and RP are available.

TYRP1 mRNA expression in melanoma metastases correlates with clinical outcome.

BACKGROUND: Clinical outcome of patients with high-risk melanoma cannot be reliably predicted on the basis of classical histopathological examination. Our study aimed to determine in melanoma metastases a gene expression profile associated with patient survival, and to identify and validate marker(s) of poor clinical outcome. METHODS: Skin and lymph node metastases from melanoma patients (training population) were used to identify candidate prognostic marker(s) based on DNA microarray analysis. Additional skin metastases (validation population) were used to assess the prognostic value of the first ranked gene by real-time PCR. RESULTS: We performed microarray analysis in the training population and generated a list of 278 probe sets associated with a shorter survival. We used the first ranked gene, tyrosinase-related protein 1 (TYRP1), further measured its expression in the validation population by real-time PCR and found it to be significantly correlated with distant metastasis-free survival (DMFS), overall survival (OS) and Breslow thickness. We also found that it was fairly well conserved in the course of the disease regardless of the delay to metastasis occurrence. Finally, although Tyrp1 protein (immunohistochemistry (IHC)) was only detected in about half of the samples, we showed that its expression also correlated with Breslow thickness. CONCLUSION: Our data indicate that TYRP1 mRNA expression level, at least in skin metastases, is a prognostic marker for melanoma, and is particularly useful when prognostic pathology parameters at the primary lesion are lacking. Its conserved expression further supports its use as a target for therapy.

Pegfilgrastim and daily granulocyte colony-stimulating factor: patterns of use and neutropenia-related outcomes in cancer patients in Spain--results of the LEARN Study.

Daily granulocyte colony-stimulating factors [(G-CSFs); e.g. filgrastim, lenograstim] are frequently used to reduce the duration of chemotherapy-induced neutropenia (CIN) and the incidence of febrile neutropenia (FN) in cancer patients. A pegylated formulation of filgrastim, pegfilgrastim, which is administered once per cycle, was introduced in Spain in 2003. LEARN was a multi-centre, retrospective, observational study in Spain comparing patterns of use of daily G-CSF and pegfilgrastim, and CIN-related outcomes in adults with non-myeloid malignancies receiving myelosuppressive chemotherapy. Outcome measures were the percentage of patients receiving G-CSF for primary prophylaxis versus secondary prophylaxis/treatment, duration of treatment with G-CSF and incidence of CIN-related complications. Medical records from consecutive patients with documented pegfilgrastim (n = 75) or daily G-CSF (n = 111) use during 2003 were included. The proportion of patients receiving primary or secondary prophylaxis was comparable between the pegfilgrastim (39 and 48% respectively) and daily G-CSF (40 and 48% respectively) groups. However, there was a trend towards less frequent use to treat a neutropenic event such as FN or neutropenia in the pegfilgrastim group (17 versus 30% with daily G-CSF). Chemotherapy-induced neutropenia-related complications were less frequent in patients receiving pegfilgrastim (e.g. FN 11 versus 24% with daily G-CSF). This is the first study to show the potential benefits of pegfilgrastim over daily G-CSF in Spanish clinical practice.

Epirubicin-cyclophosphamide adjuvant chemotherapy plus tamoxifen administered concurrently versus sequentially: randomized phase III trial in postmenopausal node-positive breast cancer patients. A GEICAM 9401 study.

BACKGROUND: A prospective randomized clinical trial was implemented to assess whether the concomitant or the sequential addition of tamoxifen to chemotherapy provides improved clinical benefit in the adjuvant treatment of breast cancer in postmenopausal patients. PATIENTS AND METHODS: Four-hundred and eighty-five patients with node-positive operable disease were randomized to receive tamoxifen (20 mg/day) concomitantly (CON) or sequentially (SEQ) to EC chemotherapy (epirubicin 75 mg/m(2) + cyclophosphamide 600 mg/m(2) on day 1, every 21 days for four cycles). RESULTS: In the 474 fully evaluable patients there were 96 events; eight being second neoplasms and 88 being related to the breast cancer. Of these, 48 of 88 occurred in the CON arm and 40 of 88 in the SEQ arm. The Kaplan-Meier estimation of disease-free survival (DFS) at 5 years was 70% in the CON and 75% in the SEQ group (log-rank test, P = 0.43). Adjusted hazard ratio for treatment was 1.11 (95% confidence interval 0.71-1.73; P = 0.64). CONCLUSION: This study fails to show an advantage of one treatment arm over the other, but a trend, albeit non-significant, appears to favor the sequential addition of tamoxifen to epirubicin + cyclophosphamide and, as such, warrants further investigation.

Reservorios venosos subcutáneos: disección versus punción / Subcutaneous venous indwelling: cutdown versus percutaneous puncture insertion

- Propósito: Los reservorios venosos subcutáneos (RVS) pueden ser implantados por punción o mediante disección. El objetivo de este estudio es comparar ambas técnicas.- Material y métodos: De una serie de 237 RVS (Healthport,, Baxter, Lessines, Belgica), 100 pacientes fueron aleatorizados a colocación por disección (CD) o por punción percutánea (PP). Los datos demográficos, complicaciones y duración del RVS (definida como duración hasta retirada, último control o exitus del paciente) fueron recogidos en un protocolo prospectivo. Las complicaciones en cada grupo fueron comparadas mediante el test de Fisher.- Resultados: El grupo CD constó de 20 hombres y 30 mujeres (16 cánceres de mama, 10 colorrectales, 6 linfomas, 6 cánceres de pulmón, 6 tumores ORL, 2 mielomas, 2 melanomas y 2 tumores ováricos) con una media de edad de 58.6 años (rango 19-83). El grupo PP constó de 23 hombres y 27 mujeres (20 cánceres colorrectales, 13 mamarios, 5 pulmonares, 5 gástricos, 2 melanomas, 2 ORL, 2 ováricos y 1 linfoma) con una media de edad de 58.2 años (rango 43-76). El grupo CD tuvo 4 (8 por ciento) complicaciones (2 oclusiones, 1 trombosis y 1 mal posición). El grupo PP tuvo 1 (2 por ciento) complicación (trombosis). El grupo CD tuvo una media de tiempo de duración del RVS de 214 días mientras que en el grupo PP fue de 201 días. El test de Fisher (complicaciones) resultó con un valor de 0.152, al que corresponde un p>0.05.- Conclusiones: En nuestra experiencia, la colocación de RVS por disección tiene un índice de complicaciones superior a la colocación mediante punción percutánea. Sin embargo, este aumento del índice de complicaciones no alcanza significancia estadística (AU)

Synthetic undecapeptide (NTX10-20) of noxiustoxin blocks completely the I(A) potassium currents of cerebellum granular cells.

Native noxiustoxin (NTX) and synthetic peptides corresponding to its primary sequence, from positions 1-9, 1-14, 1-20, 10-20, 21-39 and 30 39, were prepared and assayed on the K+ currents of cerebellum granular cells, using the patch-clamp technique in the whole-cell configuration system. Native toxin has a reversible inhibitory effect (IC50 = 360 nM), whereas synthetic peptides NTXI-20 and NTX1-9 had a half-effective dose IC50 of approximately 2 and 10 microM, respectively, which correlates with their biological effects in vivo. Synthetic peptide NTX10-20 was quite remarkable in having a preference for the IA current, which was completely inhibited at high peptide concentration. The effects of the other peptides (NTXI 14, NTX21-39 and NTX30-39), although positive and reversible, required higher concentrations (50 200 microM) to block both currents, suggesting no affinity or, at least, much lower specificity for the channels responsible for the potassium currents in the granular cells studied.

Phase II study of ifosfamide plus vinorelbine in metastatic breast cancer patients previously treated with combination chemotherapy.

Forty-six patients were included in a phase II study to evaluate the response rate and toxicity of a combination of ifosfamide and vinorelbine in metastatic breast cancer patients previously treated with one or more regimens of chemotherapy. Treatment consisted of ifosfamide 1.6 g/m(2) IV days 1-3 (with mesna) and vinorelbine 25 mg/m(2) IV days 1 and 8, every 3 weeks up to 6 cycles. The median age was 55 years (range 40-76), the World Health Organization (WHO) performance status was 0-1 in 93% of the patients and 2 in the remaining 7%. In all, 43% had received two or more previous lines of chemotherapy, and 91% had been treated with anthracyclines. Forty-four patients were evaluable for response, and all patients for toxicity. The overall response rate was 36.4% [95% confidence interval (CI) 22.4-52.2]. Stabilization was observed in 20.4% and progression in 43.2%. The median time to progression was 25 weeks (95% CI 14-36). Median relative dose intensity (=actual received dose intensity/planned dose intensity) was 0.99 for ifosfamide and 0. 80 for vinorelbine. The main toxicity was hematological, with 63% of the patients experiencing grade 3-4 neutropenia. With a moderate toxicity, this is an active regimen that may be taken into consideration in pretreated metastatic breast cancer patients when further chemotherapy is indicated.

A randomized phase II trial of 5-fluorouracil, with or without human interferon-beta, for advanced colorectal cancer.

This study compared the efficacy and safety of 5-fluorouracil (5-FU) monotherapy to that of 5-FU combined with natural human interferon-beta (IFN-beta) in patients with unresectable, advanced colorectal carcinoma. Forty-nine chemotherapy-naive patients were randomized to 5-FU alone or to the combination. All patients received 750 mg m(-2) day(-1) 5-FU for 5 days by continuous intravenous (i.v.) infusion, followed after day 15 by a weekly i.v. bolus of 750 mg m(-2). IFN-beta was injected intramuscularly three times weekly at 9 M IU. Treatment continued for 52 weeks, or until disease progression or intolerable toxicity. Clinical endpoints were tumor response, time to progression, survival and toxicity. The addition of IFN-3 to 5-FU significantly improved response rate (33.3% vs 4.5% for evaluable patients; P = 0.021), time to progression (median 7.2 vs 4.2 months; P = 0.0435), and survival time (median 15.9 vs 7.2 months; P = 0.038) without significantly increasing toxicity compared to 5-FU alone. Cumulative 5-FU dose was higher with combined therapy (P < 0.001): more patients receiving monotherapy discontinued treatment because of disease progression. Fever was more frequent with combined therapy (P = 0.008); there were no other differences in toxicity. The only grade IV toxicity observed was neutropenia (two patients per group). A randomized phase III trial has been initiated to confirm the synergy between 5-FU and IFN-beta.

Potentiation of gentamicin nephrotoxicity in the rat by infusion of aprotinin.

The present study was undertaken to examine a possible effect of aprotinin, a 6.5-kDa polypeptide with an inhibitory effect on proteolysis, on aminoglycoside nephrotoxicity. Experimental animals (female Sprague-Dawley rats, 175-200 g body wt) were treated for 4 days with 40 mg/kg gentamicin given ip at 12-hr intervals. Aprotinin (40,000 kIU per animal) was infused i.v. over a period of 8 days, using subcutaneously implanted miniosmotic pumps. In protocol A, infusion pumps were placed 4 days before starting gentamicin treatment. In protocol B, pumps were implanted 15-18 hr prior to first gentamicin administration. In addition to rats exposed to both gentamicin and aprotinin (GAP), animals were treated with gentamicin ip+saline i.v. (G), saline ip+aprotinin i.v. (AP), or received only saline by both routes of administration (C). All rats were terminated 4 days after the end of gentamicin dosing. One hour before sacrifice, 200 microCi of [3H]thymidine was given ip to each animal in order to monitor cell turnover in renal tissue. The kidneys were analyzed with respect to (i) histopathological alterations and renal dysfunction, (ii) aminoglycoside tissue accumulation, and (iii) tubular regeneration (measurement of cell proliferation). In animals receiving aprotinin alone, histological examination of renal cortex on paraffin sections disclosed mild tubular injury with focal cell necrosis. In plastic-embedded tissue, proximal tubule epithelium was characterized by the presence of numerous inclusions densely stained with toluidine blue. At the ultrastructural level, these inclusions appeared filled with amorphous electron-dense material. In gentamicin-treated animals, cortical drug accumulation reached values higher than 0.3 mg/g renal tissue, but a significant 30-40% decrease of gentamicin accumulation was noted in GAP groups, compared to G groups. Histological examination of renal cortex (paraffin sections) revealed the development of acute tubular necrosis in both G and GAP groups. Tubular injury was accompanied by mild renal dysfunction, as shown by the level of serum creatinine which was increased almost 3-fold in the G group, compared to C and AP groups. Aprotinin infusion produced a further increase of serum creatinine, particularly in protocol A where it was 72% higher for the GAP group than for the G group. In both G and GAP groups, postnecrotic tubular regeneration was evidenced by determining the rate of DNA synthesis and the frequency of S-phase cells in renal cortex. Both methods gave consistent results and showed a 8- to 13-fold increase of cell proliferation in groups receiving gentamicin alone, compared to C groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Gamma radiation-induced differentiation on human neuroblastoma cells in culture.

We have studied the effect of gamma radiation on differentiation in neuroblastoma cell lines AF8 and SJ-N-KP. Growth inhibition and morphological and biochemical differentiation have been examined following radiation exposure to 1-10 Gy. Gamma radiation induced marked growth inhibition and morphological differentiation in a dose-and time-dependent manner in both cell lines, and induced biochemical differentiation in AF8 cells.