Analysis of viral pneumonia and risk factors associated with severity of influenza virus infection in hospitalized patients from 2012 to 2016.

BACKGROUND: Influenza viruses cause pneumonia in approximately one-third of cases, and pneumonia is an important cause of death. The aim was to identify risk factors associated with severity and those that could predict the development of pneumonia. METHODS: This retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during four influenza seasons in Spain (October to May) from to 2012-2016. RESULTS: Overall, 666 patients with laboratory-confirmed influenza were included, 93 (14%) of which were severe; 73 (10.9%) were admitted to Intensive Care Unit (ICU), 39 (5.8%) died, and 185 (27.7%) developed pneumonia. Compared to less severe cases, patients with severe disease: were less vaccinated (40% vs. 28%, p = 0.021); presented with more confusion (26.9% vs. 6.8%), were more hypoxemic (Horowitz index (PaO2/FiO2) 261 vs. 280), had higher C-reactive protein (CRP) (12.3 vs. 4.0), had more coinfections (26.8% vs. 6.3%) and had more pleural effusion (14% vs. 2.6%) (last six all p < 0.001). Risk factors significantly associated with severity were pneumonia [OR (95% CI) = 4.14 (2.4-7.16)], history of heart disease (1.84, 1.03-3.28), and confusion at admission (4.99, 2.55-9.74). Influenza vaccination was protective (0.53, 0.28-0.98). Compared to those without pneumonia, the pneumonia group had higher CRP (11.3 vs. 4.0, p < 0.001), lower oxygen saturation (92% vs. 94%, p < 0.001), were more hypoxic (PaO2/FiO2 266 vs. 281, p < 0.001), and incurred more mechanical ventilation, septic shock, admission to the ICU, and deaths (all four p < 0.001). Higher CRP and lower oxygen saturation were independent variables for predicting the development of pneumonia. CONCLUSIONS: Pneumonia, history of heart disease, confusion and no influenza vaccination were independent variables to present complications in patients admitted with influenza infection.

Role of poorly differentiated cluster in gastric cancer: is it a new prognosis factor?

BACKGROUND: Poorly differentiated Clusters (PDCs) of tumor cells composed of more than five elements have been recently described in gastrointestinal cancers and correlate with a worse prognosis. Our study aims to investigate PDC occurrence in a series of patients with gastric cancer and correlate it with lymph node status and clinical outcome. MATERIAL AND METHODS: 50 patients were included in the study; PDCs count was graduated as G1, G2, and G3 according to Ueno classification (PDCs count at 20× <5, 5-9 and ≥10 respectively). We collected several clinicopathologic variables such as tumor location, pTNM stage, vascular or perineural invasion, and lymph-node ratio for each case. RESULTS: The presence of PDCs was related to vascular invasion (p < .013) and recurrence event (p < .027). When the population was categorized according to the number of PDCs, a significant correlation was found with the presence of lymph node metastasis (p < .000), the Lymph Node Ratio (p < .002), WHO stage at the diagnosis (p < .000) and vascular invasion (p < .001). At the univariate and multivariate analysis, PDCs were found as an independent risk factor for recurrence (HR 1.94; CI 95% 1.209-3.121; p < .006 and HR 0.401; CI 95% 0.187-0.862; p < .017 respectively). The Kaplan-Meier curves for OS and DFS showed a significant association between PDCs and shorter time to recurrence or survival. CONCLUSION: PDC is a strong prognostic factor in gastric cancer, easily detectable, and feasible. As far as we know, this is the first report in Literature of a strong correlation between PDC and survival in patients with operated gastric cancer.

Treatment Following Progression in Metastatic Melanoma: the State of the Art from Scientific Literature to Clinical Need.

INTRODUCTION: In the last few years, the advent of targeted therapy and immunotherapy has improved the management and the prognosis of metastatic melanoma, but the spread of resistance mechanisms can lead to disease progression. The clinical management in this setting can be challenging because the oncologist has to decide what is the best treatment strategy among therapy beyond progression (TBP), therapy change, and the rechallenge approach. This review of the relevant scientific literature is intended to clarify which patients with progressing metastatic melanoma will benefit from continuation of ongoing therapy and which ones will not. The data are based on a total of about 4300 patients coming from the main retrospective studies in the chosen field. The article body is divided into four sections which analyze respectively the targeted therapy beyond progression, the immunotherapy beyond progression, the possible treatment sequences, and finally the rechallenge strategy. RECENT FINDINGS: Despite the possible approaches of TBP or rechallenge, the patient may not have an optimal response and may need new therapy, which is currently missing. To broaden the pharmacological offer in the fight against melanoma, cancer research is studying new disease targets, like the NRAS, PI3K, and cKIT pathways or combination treatment of targeted therapy plus immunotherapy. Despite the limitations of this work, mainly due to the limited number of studies, their retrospective nature and the lack of comparative studies, the analysis performed allows us to draw some important conclusions: therapy beyond progression, both targeted therapy and immunotherapy, represents a valid treatment option with positive effects on disease control and survival outcomes for patients with low clinical risk, expressed as low disease burden, normal LDH levels, and good performance status; moreover, the prognosis and quality of life of these patients improve when TBP is associated with locoregional treatments. In patients with progressive metastatic melanoma and high clinical risk (high disease burden, high LDH levels, and poor performance status), it is recommended to change therapy, without ever forgetting the possibility of enrolling the patient in a clinical trial. Finally, an efficacious treatment alternative is the rechallenge strategy; this approach consists in a re-treatment with the same drug after a variable interval of discontinuation. Preliminary studies seem to have demonstrated that patients retreated with targeted therapy achieved a greater benefit if they had a low clinical risk and if the drug doublet (BRAF + MEK inhibitors) was used. On the side of immunotherapy, the rechallenge strategy produced a major benefit in patients who prior experienced a severe toxic episode.

A potential risk assessment tool to monitor pathogens circulation in coastal waters.

The present study reports data on a 20 months campaign monitoring enteric viruses (hepatitis A, norovirus, rotavirus, astrovirus, sapovirus, and aichivirus) and bacteria (Salmonella spp.) in seawater. The aim of this work was to assess the potential correlation among the presence of viruses/bacteria and different environmental factors like seasonality, water discharge sources (treated and untreated wastewater, mixed waters and raw water) as well as influence of the Italian lockdown measure against COVID-19 pandemic. Results showed different prevalence of the investigated viruses with values equal to 16 % for norovirus GI, 15.1 % for norovirus GII, followed by 13.8 % for astrovirus, and 13.3 % for sapovirus. Rotavirus was detected in the 8.4 % of samples and aichivirus was detected with the lowest prevalence of 3.5 %. Hepatitis A virus was never identified in the monitoring campaign. Salmonella spp. was detected with a prevalence of 36.6 %. Statistical analysis displayed a high correlation for the two noroviruses simultaneous detection (NGI and NGII) while a lower correlation was found for co-presence of noroviruses with astrovirus, sapovirus or Salmonella spp. A significant decrease of enteric pathogens in seawater was observed during the restrictions period. Results on seasonality highlighted a higher viral prevalence correlated to the wet season for all the pathogens but rotavirus and aichivirus, which instead showed an opposite trend and a higher incidence in the dry season. With respect to discharge typology, some viruses displayed a higher prevalence in treated waters (astrovirus, rotavirus, sapovirus and aichivirus) while the other investigated pathogens (noroviruses and Salmonella spp.) showed a higher prevalence in mixed waters. The main observations of this work were used to define a potential monitoring strategy that could be useful for sanitary Authorities to implement surveillance plans aimed at preventing possible sanitary outbreaks and/or environmental quality deterioration.

Atypical variants of bovine spongiform encephalopathy: rare diseases with consequences for BSE surveillance and control.

INTRODUCTION: Occurring for the first time in 1986 in the United Kingdom, bovine spongiform encephalopathy (BSE), the so-called "mad-cow disease", has had unprecedented consequences in veterinary public health. The implementation of drastic measures, including the ban of meat-and-bone-meal from livestock feed and the removal of specified risk materials from the food chain has eventually resulted in a significant decline of the epidemic. The disease was long thought to be caused by a single agent, but since the introduction of immunochemical diagnostic techniques, evidence of a phenotypic variation of BSE has emerged. Reviewing the literature available on the subject, this paper briefly summarizes the current knowledge about these atypical forms of BSE and discusses the consequences of their occurrence for disease control measures.

INTRODUCTION: L'encéphalopathie spongiforme bovine (ESB) dite aussi "maladie de la vache folle", apparue pour la première fois en 1996 au Royaume-Uni, a eu des conséquences sans équivalent pour le service public vétérinaire. La mise en application de mesures de lutte drastique, telle l'interdiction d'affourager les animaux de rente avec des farines animales et le retrait de la chaine des aliments de matériels à risque a conduit à un recul significatif de l'épidémie. Durant longtemps on a considéré que la maladie n'était causée que par un seul type de l'agent infectieux. Avec l'introduction de techniques de diagnostic immunochimiques, on a toutefois des indices de variantes phénotypiques de l'ESB. Le présent article résume la littérature disponible et fait le point des connaissances quant à ces variantes atypiques de l'ESB; on y discute également les conséquences possibles de leur apparition quant à la lutte contre la maladie.

Prognostic factors in gastric cancer patients: a 10-year mono-institutional experience.

Introduction: Gastric cancer (GC) is one of the main causes of death from cancer globally. Long-term survival, especially in Western countries, remains dismal, with no significant improvements in recent years. Therefore, precise identification of clinical and pathological risk factors is crucial for prognosis, as it allows a better selection of patients suitable for oncologically radical treatments and contributes to longer survivals. Methods: We devised a retrospective observational longitudinal study over 10 years of experience with GC patients operated with curative intent. Results: Several factors were thoroughly investigated in a multivariate analysis to look for significance as independent risk factors for disease-free survival. Our results showed that only BMI, pTNM, and lymph node ratio expressed hazard ratios with implications for survival in our series of patients. Discussion: Although limited by the retrospective nature of the study, this is one of the few cancer reports from Northern Italy showing results over 10 years, which may in our view, have an impact on decision-making processes for multidisciplinary teams dedicated to the care of gastric cancer patients.

Emergence and dissemination of epidemic-causing OXA-244 carbapenemase-producing Escherichia coli ST38 through hospital sewage in Norway, 2020-2022.

BACKGROUND: Population-based sewage surveillance has emerged as a promising approach for studying the prevalence of antibiotic resistance in pathogens. AIM: To determine the temporal prevalence of cefotaxime-resistant Escherichia coli in sewage from five sewage treatment plants located in Bergen city, to determine whether ESBL- and carbapenemase-producing E. coli are consistently disseminated in the receiving environment through sewage. METHOD: A total of 569 cefotaxime-resistant E. coli were isolated over a period of 19 months (August 2020 to February 2022) using ECC CHROMagar™ plates from 82 samples, antibiotic sensitivity profiles were determined, using Sensititre™ plates. The draft genome sequences were determined, using Illumina MiSeq-based sequencing. Complete genome sequences were determined, using Oxford Nanopore-based sequencing. FINDINGS: All 569 strains obtained from influent (N=461) and effluent (N=108) were multi-drug resistant. Most of the sequenced strains (52 of 61) carried blaCTX-M-15 (38.5%) and blaCTX-M-27 (34.6%). The most prevalent sequence types (STs) for ESBL-carrying strains were ST131 (32.8%) and ST38 (21.3%). All CTX-M-27-carrying ST131 strains belonged to clade A or C1, while CTX-M-15-harbouring strains were present in all the clades. Five OXA-244-producing ST38 strains, genetically similar to epidemic-causing strains from Western Norway, France and the Netherlands, were isolated only from raw and treated sewage of the treatment plant receiving hospital sewage. CONCLUSION: This is the first study showing persistent dissemination of OXA-244-producing ST38 clones through sewage in Norway, demonstrating that hospital sewage is the likely source of OXA-244-producing ST38 clones reaching the receiving environment.

Advanced Parkinson's disease: clinical characteristics and treatment. Part II.

INTRODUCTION: Many patients who have had Parkinson's disease (PD) for several years will present severe motor fluctuations and dyskinesias which require more aggressive therapies. The different approaches which are now available include deep brain stimulation of the subthalamic nucleus or medial globus pallidus, subcutaneous infusion of apomorphine, and intestinal infusion of levodopa-carbidopa. OBJECTIVE: To define the indications and results for the 3 available therapies for advanced PD. DEVELOPMENT: Exhaustive review of the literature concerning the indications and results of deep brain stimulation, subcutaneous apomorphine infusion and duodenal infusion of levodopa/carbidopa gel to treat patients with advanced Parkinson disease. CONCLUSIONS: Although numerous studies have confirmed the efficacy of the 3 different therapies in advanced PD, there are no comparative studies that would allow us to define the best candidate for each technique.

[Advanced Parkinson's disease: clinical characteristics and treatment (part 1)]. / Enfermedad de Parkinson avanzada. Características clínicas y tratamiento (parte I).

INTRODUCTION: A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. OBJECTIVE: To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. DEVELOPMENT: This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). CONCLUSIONS: Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD.

Alterations in the odor profile of plants in cultivar mixtures affect aphid host-location behavior.

The effect of cultivar mixtures on aphid control is attributed to the masking or alteration of host-preferred cultivar odor cues. However, the underlying physiological mechanism remains unclear. This study assessed alterations in the volatile emissions of wheat cultivars grown together (Florence-Aurora and Forment; Florence-Aurora and Montcada) and the consequences for the olfactory preference of aphids. Volatile organic compounds were collected from wheat plants grown in a laboratory under mixed or monoculture conditions and subsequently analyzed. The odor profiles of Florence-Aurora and Montcada were indistinguishable from each other. However, the odors of Florence-Aurora and Forment grown in monocultures differed significantly from those emitted by their mixture. The Florence-Aurora and Forment mixture induced plant physiological responses that affected the emission of single volatile compounds and, consequently, altered volatile organic compound ratios. English grain aphids (Sitobion avenae) were less attracted to the odors of Florence-Aurora and Forment when grown as a mixture than the combination of the odors from Florence-Aurora and Forment monocultures. Moreover, aphids preferred clean air over the odor from the Florence-Aurora and Forment mixture but preferred the odor from the Florence-Aurora and Montcada mixture over clean air. This study highlights the beneficial effects of intraspecific plant diversity on aphid control by altering plant odors in response to plant-plant interactions. The emission of less attractive odor cues consequently affects plant-aphid interactions; hence, less attractive odors are likely to impair aphid host-locating behavior. This effect was exclusive to certain cultivar mixtures, which supports the "right neighbor" concept.

Strong impact of sarcopenia as a risk factor of survival in resected gastric cancer patients: first Italian report of a Bicentric study.

Gastric cancer (GC) accounts for 4% of all cancers in Europe. Sarcopenia is a complex syndrome characterized by a loss of muscle mass and function associated with age, often present in neoplastic patients. Recently, several studies have shown a significant association between sarcopenia and poor prognosis in various pathological conditions. The current observational retrospective study investigates the association between sarcopenia and overall survival (OS) and recurrence-free survival (RFS) in patients with GC undergoing up-front surgery with curative intent. Resected GC patients' clinical records and CT images were retrospectively assessed. The preoperative CT calculation of the skeletal muscle index (SMI) at L3 level allowed us to categorize patients as sarcopenic or not. Kaplan-Meyer and univariate and multivariate Cox regression analyses were performed to determine the difference in survival and presence of independent prognostic factors. Fifty-five patients, 28 male and 27 female, out of 298 studied for gastric cancer were enrolled in the current study from two cancer referral centers in Italy. The preoperative CT calculation of the SMI at L3 level allowed us to identify 39 patients with and 16 without sarcopenia. A statistically significant difference between the sarcopenic and non-sarcopenic groups was observed in both OS and RFS (p < 0.023; p < 0.006). Moreover, sarcopenia was strongly correlated to a higher risk of recurrence in univariate and multivariate analysis (p < 0.02). Sarcopenia can be considered a critical risk factor for survival in patients with resectable GC treated with up-front surgery. Identifying sarcopenic patients at the time of diagnosis would direct selection of patients who could benefit from early nutritional and/or physical treatments able to increase their muscle mass and possibly improve the prognosis. More extensive multicenter studies are needed to address this issue.

Six-month humoral and cellular immune response to the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors: a longitudinal cohort study with a focus on the variants of concern.

BACKGROUND: The role and the durability of the immunogenicity of the third dose of vaccine against COVID-19 variants of concern in cancer patients have to be elucidated. PATIENTS AND METHODS: We have prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 messenger RNA vaccine in triggering both humoral and cell-mediated immune response in patients with solid tumors undergoing active treatment 6 months after the booster. Neutralizing antibody (NT Ab) titers and total anti-spike immunoglobulin G concentrations were measured in serum. Heparinized whole blood samples were used for the SARS-CoV-2 interferon-γ release assay (IGRA). RESULTS: Six months after the third dose only two patients (2.4%) showed negative spike-specific immunoglobulin G antibody levels (<33.8 BAU/ml). The median level of SARS-CoV-2 NT Abs decreased and only 39/83 (47%) subjects showed maximum levels of NT Abs. T-cellular positive response was observed in 38/61 (62.3%) patients; the highest median level of response was observed 21 days after the third dose (354 mIU/ml, interquartile range 83.3-846.3 mIU/ml). The lowest median level of NT Ab response was observed against the Omicron variant (1 : 10, interquartile range 1 : 10-1 : 40) with a significant reduced rate of responder subjects with respect to the wild-type strain (77.5% versus 95%; P = 0.0022) and Delta variant (77.5% versus 93.7%; P = 0.0053). During the follow-up period, seven patients (8%) had a confirmed post-vaccination infection, but none of them required hospitalization or oxygen therapy. CONCLUSIONS: Our work highlights a significant humoral and cellular immune response among patients with solid tumors 6 months after the third BNT162b2 vaccine dose, although a reduction in neutralizing activity against Omicron was observed.

Corneal hemangiosarcoma in a cat.

A 10 year-old castrated male Domestic Short-hair cat with a history of chronic bilateral keratitis was referred for assessment of a red, elevated mass involving the left cornea. The rapid growth of the mass, over a month period in combination with pronounced vascularization and invasion of the corneal surface suggested an aggressive inflammatory or neoplastic process. Following keratectomy, the lesion was diagnosed histopathologically as a hemangiosarcoma. The tumor recurred locally within 3 weeks and enucleation was performed. Histopathologic examination of the globe confirmed the diagnosis and did not reveal infiltration of the limbus and conjunctiva. No signs of local recurrence or metastatic disease have been observed 18 months following enucleation. To the authors' knowledge this is the first case of primary corneal hemangiosarcoma described in the feline species.

Efficacy of an alpha-hydroxy acid (AHA)-based cream, even in monotherapy, in patients with mild-moderate acne.

AIM AND METHODS: The treatment of mild-moderate acne with topical drugs in association with appropriate cosmetics is currently the golden standard. The tolerability and efficacy of a cream formulated with a new mix of alpha-hydroxy acids (Hyseac AHA cream) in 248 patients with mild-moderate acne (comedonic, inflammatory, or mixed) have been investigated in a multicenter, non-randomized, open study by 10 dermatologists from different Italian areas during their routine practice. The medication with Hyseac AHA cream was prescribed at first consultation for 60 days, twice a day, either as a monotherapy (49.2% patients) or in association with a pharmacological treatment (50.2%). RESULTS: The tolerability was good to excellent in 92.3% patients, without significant differences between patients using AHA cream in monotherapy (90.0%) or associated with concomitant pharmacological treatment (97.6%). The efficacy was overall high in 64.2% patients, again without significant differences related to concomitant pharmacological treatment or not (64.8% vs. 63.3%) and/or the acne clinical type (comedonic vs. inflammatory vs. mixed: 69.2% vs. 66.7% vs. 58%). CONCLUSION: The results of this study, while confirming the high tolerability and efficacy of this AHA cream in the treatment of mild/moderate acne, reasonably suggest its possible use also in monotherapy. Furthermore, its use can be reasonably hypothesized as a maintenance treatment after specific pharmacological treatment even in more severe acne types.

Negative pressure wound therapy (NPWT) after cytoreductive surgery (CRS) and intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies: preliminary report.

AIM: Surgical site (SSI) infection is a common complication that occurs in the post-operative period because it still has a decisive impact on the morbidity and mortality of patients and the costs associated with therapy and prolongation of hospitalization. In recent years, therefore, several authors have published their experience in the use of negative pressure prevention systems (NPWT) for the management of surgical wounds. Few authors in the literature have discussed the use of NPWT in patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies associated with hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: Nineteen patients undergoing open surgery, of which 15 underwent CRS+HIPEC operations; in 2 cases the dressing was applied to patients undergoing colon surgery, 1 case after emergency laparotomy for intestinal occlusion in a patient with a BMI of 29 and 1 case after gastric surgery for a tumour. At the and of the surgery, NPWT was placed on the surgical site; the therapy includes a closed and sealed system which maintains a negative pressure between at -125 mmHg on the surgical wound and which remains in place for five days. RESULTS: The rationale for using an NPWT is to determine a barrier between the wound and external contamination, reducing wound tension and reducing the formation of seroma and hematoma. Moreover, during the HIPEC, several litres of water are used to wash the patient's abdominal cavity and then the patient is sutured again without the peritoneum, losing the function of protection from external microorganism and also of reabsorbing the intra-abdominal serum. A recent Cochrane collaboration about the application of NPWT demonstrates that it may reduce the rate of SSI compared with SSD, even if there is no sure evidence about the reduction of complications like seromas or dehiscence. CONCLUSION: After the analysis of the preliminary data, we confirm the possibility to start with a randomised clinical trial, as suggested by the literature.

Presumptive BSE cases with an aberrant prion protein phenotype in Switzerland, 2011: Lack of prion disease in experimentally inoculated cattle and bovine prion protein transgenic mice.

Bovine spongiform encephalopathy (BSE) is caused by different prion strains that are discriminated by the molecular characteristics of the pathological prion protein. In 2011, Switzerland reported two presumptive cases of BSE in cattle with a prion protein phenotype different from previously described strains, and it was unclear whether these findings were related to a transmissible disease and have implications on animal and public health. In this study, brain tissues of these cases were inoculated into transgenic mice expressing the bovine prion protein (BoPrP-Tg110) and into cattle. Clinical and pathological investigations as well as molecular testing did not provide evidence for the presence of BSE in the Swiss cases after two passages in BoPrP-Tg110 mice and a challenge period of 3.5 years in cattle. This lack of disease transmission suggests that the Swiss 2011 cases were not affected by a prion disease and were unrelated to the feed-born BSE epidemic.

Complete genome sequence of the marine Rhodococcus sp. H-CA8f isolated from Comau fjord in Northern Patagonia, Chile.

Rhodococcus sp. H-CA8f was isolated from marine sediments obtained from the Comau fjord, located in Northern Chilean Patagonia. Whole-genome sequencing was achieved using PacBio RS II platform, comprising one closed, complete chromosome of 6,19 Mbp with a 62.45% G + C content. The chromosome harbours several metabolic pathways providing a wide catabolic potential, where the upper biphenyl route is described. Also, Rhodococcus sp. H-CA8f bears one linear mega-plasmid of 301 Kbp and 62.34% of G + C content, where genomic analyses demonstrated that it is constituted mostly by putative ORFs with unknown functions, representing a novel genetic feature. These genetic characteristics provide relevant insights regarding Chilean marine actinobacterial strains.

Inter-laboratory comparison of elemental analysis and gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS). Part I: delta13C measurements of selected compounds for the development of an isotopic Grob-test.

This study was directed towards investigating suitable compounds to be used as stable isotope reference materials for gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) calibration. Several compounds were selected from those used in the 'Grob-test' mixture. Oxygen- and nitrogen-containing substances were added to these compounds to allow the mixture to be used as a possible multi-isotopic calibration tool for 2H/1H, 13C/12C, 15N/14N and 18O/16O ratio determinations. In this paper we present the results of delta13C measurements performed by the consortium of the five laboratories taking part in this inter-calibration exercise. All the compounds were individually assessed for homogeneity, short-term stability and long-term stability by means of EA-IRMS, as required by the bureau communitaire de reference (BCR) Guide for Production of Certified Reference Materials. The results were compared then with the GC-C-IRMS measurements using both polar and non-polar columns, and the final mixture of selected compounds underwent a further certification exercise assessing limits of accuracy and reproducibility under specified GC-C-IRMS conditions.

Methyl-p-hydroxyphenyllactate-esterase activity in breast cancer: a potentially new prognostic factor in short-term follow-up.

We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 48 cases of primary breast cancer. MeHPLAase activity did not show significant correlation with estrogen receptor and progesterone receptor levels. No significant relationship was found between enzymatic activity and tumor diameter, lymph node status, mitotic activity, degree of nuclear differentiation, and proportion of the S-phase fraction. During the follow-up period (median, 18.8 months; range, 6-69 months), recurrences were observed in 18 of 48 (37%) cases. The Weibull survival regression model using the enzymatic activity as a continuous covariate showed that levels of enzymatic activity were directly associated with the risk of recurrence (P = 0.02). Assuming the mean value of enzymatic activity as the cutoff value, we found a statistically significant relationship between high MeHPLAase activity and shorter recurrence-free survival. On multivariate analysis, MeHPLAase activity proved to be an independent factor for predicting a short period of recurrence-free survival.