Correction to: Merkel Cell Carcinoma Outcomes: Does AJCC8 Underestimate Survival?

C.R. Farley and M.C. Perez contributed equally to this publication and are co-first authors. J.S. Zager and M.C. Lowe contributed equally to this publication and are co-corresponding authors.

Merkel Cell Carcinoma Outcomes: Does AJCC8 Underestimate Survival?

INTRODUCTION: The eighth edition of the American Joint Committee on Cancer (AJCC8) Staging Manual provides important information for staging and prognostication; however, survival estimates for patients with Stage I-III Merkel cell carcinoma (MCC), a rare disease, may be as practical using data from large-volume centers as that collated for the AJCC analysis. As such, we compared our institutional outcomes to AJCC8. METHODS: Patients who presented from 2005 to 2017 with MCC to two high-volume centers were included. Demographics, clinicopathologic characteristics, survival and recurrence data were compiled, and outcomes compared to AJCC8. RESULTS: A total of 409 patients were included. Median age was 75 (range 29-98) years, and 68% were male. Median follow-up was 16 months (0-157). Five-year overall survival (OS) was 70%; 5-year disease-specific survival (DSS) was 84%. When stratified by extent of disease, 5-year OS was higher for patients with local disease compared to those with nodal disease (72.6% vs 62.7%, p=0.005). Similarly, patients with local disease had higher 5-year DSS than those with nodal disease (90.1% vs 76.8%, p=0.002). Five-year recurrence-free survival was 59.2% for all patients, 65.0% for local disease and 48.3% for nodal disease (p=0.033). CONCLUSIONS: Here, MCC patients with local or nodal disease have substantially higher OS rates than predicted in AJCC8 (5-year: 72.6% vs 50.6%; 62.7% vs 35.4%, respectively). Importantly, 5-year DSS was significantly better than the OS rates reported presently and in AJCC8. As clinicians and patients rely on AJCC to accurately prognosticate and guide treatment decisions, these estimates should be reassessed and updated to more accurately predict survival outcomes.

Real-world short-term effectiveness of ustekinumab in 305 patients with Crohn's disease: results from the ENEIDA registry.

BACKGROUND: There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM: To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS: Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (<250 µg/g) in 46% and 54% of the patients at weeks 8 and 14 respectively. CRP returned to normal (<3 mg/L) in the 35% and 41% of the patients at week 8 and 14 respectively. AEs were recorded in 38, and 40 patients were hospitalised. Intolerance to the most recent anti-TNF agent and fewer previous anti-TNF agents were associated with clinical remission at week 14. Endoscopic severity was associated with poor response. CONCLUSION: This is the first study to show the real-world effectiveness and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.

[Application of the Smoking Scale for Primary Care (ETAP) in clinical practice]. / Aplicación de la Escala de Tabaquismo para Atención Primaria (ETAP) en la práctica clínica.

OBJECTIVE: To determine if the ETAP smoking scale, which measures accumulated exposure to tobacco, both actively and passively, is applicable and effective in the clinical practice of Primary Care for the prevention of acute myocardial infarction (AMI). Location Barranco Grande Health Centre in Tenerife, Spain. DESIGN: A study of 61 cases (AMI) and 144 controls. Sampling with random start, without matching. COR-II curves were analysed, and effectiveness was estimated using sensitivity and negative predictive value (NPV). A questionnaire was provided to participating family physicians on the applicability of ETAP in the clinic. RESULTS: The opinion of the participating physicians was unanimously favourable. ETAP was easy to use in the clinic, required less than 3min per patient, and was useful to reinforce the preventive intervention. The ETAP COR-II curve showed that 20years of exposure was the best cut-off point, with an area under the curve of 0.70 (95%CI: 0.62-0.78), and a combination of sensitivity (98%) and NPV (96%) for AMI. When stratifying age and gender, all groups achieved sensitivities and NPVs close to 100%, except for men aged ≥55years, in whom the NPV fell to 75%. CONCLUSIONS: The results indicate that ETAP is a valid tool that can be applied and be effective in the clinical practice of Primary Care for the prevention of AMI related to smoking exposure.

Programa integral para el cáncer en Cuba: Pautas para la gestión de implementación / Comprehensive program for cancer in Cuba: Guidelines for implementation management

Esta nueva edición sirve de orientación en la planificación y aplicación de intervenciones dirigidas a integrar el control del cáncer a las acciones del sistema nacional de salud, basa su actualización en el programa del médico y enfermera de la familia, y se estructura en paquetes tecnológicos como innovación para incorporar entre otros, los productos de la biotecnología. En ese sentido, organiza la gestión direccionada por el conocimiento, la socialización de las nuevas formas de organización establecidas para el control de la enfermedad.

Nonthermal Inactivation of Cronobacter sakazakii in Infant Formula Milk: A Review.

Up-to-date, nonthermal technologies and combinations of them, in accordance with the "hurdle technology" concept, are being applied by different research groups in response to calls by the International Food and Human Health Organizations (ESPGHAN, 2004; FAO/WHO, 2006, 2008) for alternatives to thermal control of Cronobacter sakazakii in reconstituted powdered infant formula milk. This review highlights (i) current knowledge on the application of nonthermal technologies to control C. sakazakii in infant formula milk and (ii) the importance of the application of nonthermal technologies for the control of C. sakazakii as part of the development of strategies in the context of improving food safety and quality of this product.

Selective removal of ATP degradation products from food matrices II: Rapid screening of hypoxanthine and inosine by molecularly imprinted matrix solid-phase dispersion for evaluation of fish freshness.

A water compatible molecularly imprinted polymer (MIP), synthesized using theophylline (TPH) as dummy-template and acrylamide (AM) as functional monomer, has been employed as supporting material in matrix solid-phase dispersion combined with ultra performance liquid chromatography-photodiode array detection (MSPD-UPLC-PDA) for selective determination of adenosine triphosphate (ATP) derivatives in fish samples. ATP degradation products are used as freshness index for assessment of fish quality. The solid sample was directly blended with MIP in MSPD procedure resulting in sample disruption and subsequent adsorption of the compounds on the MIP. By using n-hexane and ammonium hydroxide aqueous solution at pH 9 as the washing and elution solvent, respectively, satisfactory recoveries and clean chromatograms have been obtained. Good linearity for hypoxanthine (HYP) and inosine (INO) has been observed with correlation coefficients (R(2)) of 0.9987 and 0.9986, respectively. The recoveries of the two ATP derivatives at three different spiked levels ranged from 106.5% to 113.4% for HYP and from 103.1% to 111.2% for INO, with average relative standard deviations lower than 4.2% in both cases. This new method, which is rapid, simple and sensitive, can be used as an alternative tool to conventional tedious methods.

Abatement of styrene waste gas emission by biofilter and biotrickling filter: comparison of packing materials and inoculation procedures.

The removal of styrene was studied using two biofilters packed with peat and coconut fibre (BF1-P and BF2-C, respectively) and one biotrickling filter (BTF) packed with plastic rings. Two inoculation procedures were applied: an enriched culture with strain Pseudomonas putida CECT 324 for BFs and activated sludge from a municipal wastewater treatment plant for the BTF. Inlet loads (ILs) between 10 and 45 g m(-3) h(-1) and empty bed residence times (EBRTs) from 30 to 120 s were applied. At inlet concentrations ranging between 200 and 400 mg Nm(-3), removal efficiencies between 70 % and 95 % were obtained in the three bioreactors. Maximum elimination capacities (ECs) of 81 and 39 g m(-3) h(-1) were obtained for the BF1-P and BF2-C, respectively (IL of 173 g m(-3) h(-1) and EBRT of 60 s in BF1-P; IL of 89 g m(-3) h(-1) and EBRT of 90 s in BF2-C). A maximum EC of 52 g m(-3) h(-1) was obtained for the BTF (IL of 116 g m(-3) h(-1), EBRT of 45 s). Problems regarding high pressure drop appeared in the peat BF, whereas drying episodes occurred in the coconut fibre BF. DGGE revealed that the pure culture used for BF inoculation was not detected by day 105. Although two different inoculation procedures were applied, similar styrene removal at the end of the experiments was observed. The use as inoculum of activated sludge from municipal wastewater treatment plant appears a more feasible option.

Resistance index measured by Doppler ultrasound as a predictor of graft function after kidney transplantation.

INTRODUCTION: Doppler ultrasound (US) has become the primary imaging technique for the evaluation of renal transplants. It provides information about the intrarenal resistance index (RI). A high RI is seen in every form of graft dysfunction. In this article, we review the utility of sonography, particularly the intrarenal RI measured early after renal transplant, as a predictor of acute and chronic clinical outcome in patients. RESULTS: RI is a valuable marker to determine graft function and related vascular complications. It reveals a strong correlation with serum creatinine levels measured days after transplant. Its elevation is typical for acute tubular necrosis and can be used to predict its duration. An RI >1 (absent end-diastolic flow) seen in the first weeks after transplant is associated with impaired renal graft recovery. In addition, it is an early predictor of chronic allograft nephropathy (even correlated with biopsy results), which will allow a change in therapy. CONCLUSIONS: RI measured serially in the early period after kidney transplantation is a valuable marker for determining renal graft function. It is also useful for demonstrating various types of graft dysfunction; however, it cannot differentiate between them. In recent studies, extrarenal factors in kidney transplantation (eg, recipient's age) may significantly influence RI in the recipient, demonstrating that RI depends on the vascular characteristics of the recipient and not on the graft itself.

The 12-month safety profile of dexlansoprazole, a proton pump inhibitor with a dual delayed release formulation, in patients with gastro-oesophageal reflux disease.

BACKGROUND: Dexlansoprazole MR is a Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to extend the duration of acid suppression. AIM: To assess the 12-month safety of dexlansoprazole MR in patients with symptomatic gastro-oesophageal reflux disease (GERD). METHODS: In this randomised open-label study, patients received dexlansoprazole MR 60 or 90 mg once-daily for 12 months. Safety was evaluated at months 1, 3, 6, 9 and 12/final visit through physical examinations, laboratory evaluations, endoscopies, gastric biopsies, fasting serum gastrin values and adverse events (AEs). RESULTS: Of 591 patients receiving dexlansoprazole MR 60 and 90 mg, 71% and 65%, respectively, experienced ≥1 treatment-emergent AE; the most frequent AE was upper respiratory infection (14% and 13% in the 60- and 90-mg groups). Thirty patients experienced ≥1 serious AE; a majority of serious AEs were unrelated to study drug. No clinically meaningful change in any clinical laboratory parameters was noted. As expected, serum gastrin values rose with dexlansoprazole therapy; increases were not dose related. No clinically concerning trends were identified in gastric pathology results; no endocrine cell hyperplasia, adenocarcinoma, or lymphoma were observed. CONCLUSIONS: Twelve-month treatment with dexlansoprazole MR 60 and 90 mg was well tolerated by GERD patients in this study (Clinicaltrials.gov identifier NCT00255190).

[Evaluation of urinary cortisol levels in women with fibromyalgia]. / Evaluación de la cortisoluria en mujeres diagnosticadas de fibromialgia.

OBJECTIVE: We propose a comparative study of urinary cortisol in a controlled simple group of patients diagnosed with fibromyalgia (FM) during a minimum time frame (3 years) vs. a normal group with the same characteristics of age and gender. Our objective is to demonstrate if urinary cortisol at lower levels than those found in the normal population, as long as FM is regarded, could help to evaluate the fatigue. METHODS: We determined the urinary cortisol in a group of 47 women with a clinical diagnosis of FM using the criteria from the American College of Rheumatology (ACR) 1990, with ages between 29 and 64 years, in whom an accurate sample was collected and cortisol was determined using an FPIA method. The results were compared with the urinary cortisol obtained in a group of 88 healthy women within the same age range as those with FM. RESULTS: Urinary cortisol in FM was 65.0 microg/l (median), which was significantly lower than that of the healthy group (80.0 microg/l), p<0.001. CONCLUSION: 33.4% of patients with FM displayed urinary cortisol concentrations significantly lower than the group of women without FM.

Inverse association between serum resistin and insulin resistance in humans.

AIM: To determine how serum concentrations of resistin are distributed in humans in relation to insulin resistance, type 2 diabetes, and obesity. METHODS: Cross-sectional, descriptive study carried out in a random sample (n=713, 43% men, 18-75 years) of general population of inhabitants of the Canary Islands (Spain). Serum resistin concentration, HOMA2-IR, anthropometric parameters, drug consumption and physical activity were recorded. RESULTS: There were no differences in resistin concentration between participants with and without diabetes (3.1+/-0.2 vs. 3.2+/-0.1ng/mL; p=0.566), or between obese and non-obese participants (3.1+/-0.1 vs. 3.2+/-0.1ng/mL; p=0.803). Individuals with abdominal obesity (waist-hip ratio [WHR] >or=1 in men or >or=0.9 in women) had lower concentrations of resistin (3.0+/-0.13 vs. 3.4+/-0.1ng/mL; p<0.001). The correlations between resistin and HOMA2-IR (r=-0.231; p<0.001) and between resistin and WHR (r=-0.202; p<0.001) were inverse. Multivariate analysis corroborated the inverse association of this cytokine with HOMA2-IR, WHR and, in women, also retained in the model the direct association between resistin and physical activity and the inverse association between resistin and antihypertensive agents. CONCLUSIONS: In this population resistin is inversely associated with insulin resistance and abdominal obesity.

Serum resistin and polymorphisms of androgen receptor GAGn and GGNn and aromatase TTTAn.

There is evidence that androgens are regulators of insulin resistance (IR), and may be involved in the regulation of resistin, a cytokine that has been related with IR. Earlier studies found that androgen receptor length polymorphisms CAGn and GGNn and the aromatase polymorphism TTTAn may influence receptor or enzyme activity and serum concentrations of androgens. This study was designed to determine whether polymorphism length was related to serum resistin concentration and to other variables related with IR. In 1,580 persons chosen randomly from the general population of the Canary Islands (Spain), we measured polymorphism length, waist circumference, waist/hip ratio, BMI, and serum glucose concentration. In smaller subgroups, we also measured C-peptide (n = 677), resistin (n = 583), and leptin concentration (n = 754) and estimated IR (homeostasis model assessment-IR (HOMA2-IR)). In men, polymorphism length correlated with resistin concentration (CAGn, r = 0.13, P = 0.031; TTTAn, r = 0.15, P = 0.005; GGNn, r = -0.15, P = 0.026), and the correlations were confirmed in multivariate regression models. The length of CAGn and TTTAn correlated inversely with C-peptide (r = -0.13, P = 0.016 and r = -0.21, P < 0.001, respectively) and with estimated IR (r = -0.12, P = 0.032 and r = -0.19, P = 0.001, respectively). In men, length of the CAGn, GGNn, and TTTAn was associated with serum resistin concentration. These results support the hypothesis that androgens may be involved in the regulation of resistin. Resistin may be a link between IR and androgens.

Second case of neurocysticercosis in a patient with liver transplantation (first case in Spain): a case report.

BACKGROUND: Neurocysticercosis (NCC) is a disorder caused by the Taenia solium larva. It is the most common parasitosis of the central nervous system (CNS). Its distribution is universal, but it is endemic in many developing countries and in the third world. In Spain most patients come from countries where the condition is endemic. However, sporadic cases occur among the population of rural regions. NCC in transplant recipients is uncommon. One renal transplant recipient developed NCC but responded to treatment with praziquantel. Recently, it has been reported to complicate a liver transplantation. CASE REPORT: The patient was a 49-year-old Ecuatorian man who received a cadaveric donor liver graft in June 2001 due to acute liver failure induced by toadstool and was under treatment with FK506. In January 2006, the patient presented with a generalized onset of a tonic-clonic seizure for 1 minute without sphincter incontinence, headache, fever, or previous brain trauma. Neurological evaluation did not show evidence of organic brain dysfunction. The neuroimaging findings (brain) computed tomography scan, magnetic resonance imaging were compatible with NCC: many cystic lesions intra- and extraparenchymatous with a scolex visible in three of them. Serology for cysticercosis in plasma was initially indeterminate but positive afterward. The patient was treated with anticonvulsivants (valproic acid) and albendazole. Systemic steroids were added in order to reduce the edema produced upon death of the cyst. Treatment lasted 3 weeks and it was completed without complications or neurological symptoms. Liver function was not affected. One year later the patient remained asymptomatic. CONCLUSION: NCC is a condition that must be included in the differential diagnosis of patients with CNS involvement and cystic lesions on neuroimaging investigations in transplant recipients, especially patients originating from or traveling to endemic areas. First-line therapy for active cysts includes antiparasitic drugs (albendazole or praziquantel) as well as steroids and anticonvulsivants. In our patient, this therapy was effective.

The corrosion of nickel-titanium rotary endodontic instruments in sodium hypochlorite.

AIM: To evaluate the corrosion resistance of nickel-titanium (NiTi) endodontic rotary instruments immersed in 5.25% sodium hypochlorite (NaOCl) solution. METHODOLOGY: The corrosion performance of NiTi instruments (S1 25 mm, ProTaper Dentsplay Maillefer, Ballaigues, Switzerland) was evaluated using commercial 5.25% NaOCl solution (pH = 12.3), and the same solution partially neutralized adding H2SO4 to reach pH = 10.1. Electrochemical measurements were carried out using a potentiostat equipped with a five-channel zero resistance ammeter (ZRA) for galvanic current measurements. The instruments were sectioned into three parts (cutting part, noncutting part and shank) and degreased with acetone and rinsing with demineralized water prior to being immersed in NaOCl solution for testing. Each set of the three parts constituted one 'virtual' instrument through the ZRA, giving access to the galvanic currents that circulate between the three parts. Nine instruments were employed to check the reproducibility of the electrochemical measurements. RESULTS: The corrosion potential (E(corr)) of the NiTi alloy reached the passive domain in approximately 20 s of immersion in the solution having a pH 10.1. After this initial period the potential remained steady, indicating that stable passivation was achieved. However, at pH 12.3 no stationary state was achieved even after 6000 s of immersion time. Thus, the alloy was not stable in this medium from a corrosion point of view. CONCLUSIONS: The corrosion resistance of NiTi alloy was enhanced by lowering the pH of NaOCl solution to 10.1, which allows the system to reach the stability domain of the passivating species TiO2 and NiO2.

Cytotoxic proteins combined with prodigiosin obtained from Serratia marcescens have both broad and selective cytotoxic activity on tumor cells.

Cytotoxic proteins and prodigiosin obtained from Serratia marcescens strains are known to induce tumor cell death, nevertheless its combination has not been studied. In this paper we evaluate the combined effects of these molecules in a panel of tumor cell lines. The results showed a marked inhibitory effect on the growth of tumor cell lines derived from tumors (i.e., melanoma) which are highly resistant to conventional anticancer drugs, while normal cells were less sensitive than tumor cells. TUNEL (TdT-mediated dUTP nick end labeling) and electrophoresis of HEp-2 cell DNA treated with MG2327 preparation [containing the P50 protein belonging to the serralysins and prodigiosin, from S. marcescens CMIB4202] showed a pattern of DNA fragments typically associated with apoptosis. Interestingly, prodigiosin enhanced by 1.6-fold the cytotoxic effect of P50 when acting in combination on HEp-2 cells. The broad cytotoxic activity of the combination on tumor cells as well as its selectivity open new frontiers in cancer therapy.

Effect of plane of nutrition on seasonality of reproduction in Spanish Payoya goats.

The aim of this study was to determine if there is a seasonal pattern of sexual activity in female Payoya goats and if this seasonality could be modulated by nutrition. During the experimental period of 20 months, 43 non-pregnant adults goats were penned under natural photoperiod at latitude 37 degrees 15'N. At the onset of the experiment, the animals were allocated to three experimental groups differing in the level of nutrition and whether the animals were entire or ovariectomized does. The high nutrition group (H, n = 16 entire does) receiving 1.5 times maintenance requirements. The low nutrition group (L, n = 16 entire does) and an ovariectomized and oestradiol treated group (OVX, n = 11 ovariectomized does) received a diet supporting their maintenance requirements. The groups were balanced for live weight (LW) and body condition score (BCS) at the beginning of the study. In entire goats, oestrus was tested daily using aproned males, ovulation rate was assessed by laparoscopy 7 days after identification of oestrus and plasma samples were obtained twice per week for progesterone assay. OVX goats were isolated from the other groups and bucks, plasma samples were assayed twice per week for LH and there were four intensive sampling periods during the year to determine LH pulsatility. LW and BCS were recorded for all animals once a week. A clear circannual cycle in live weight change was observed in all experimental groups, being relatively stable or slightly decreasing in summer and autumn and increasing during winter and spring. The effect of exposure to high (H) rather than low (L) nutrition was to cause earlier onset of ovarian activity (5 versus 17 August; P < 0.05), and expression of oestrous (16 August versus 2 September; P < 0.01) and later cessation of reproductive activity (ovulation 11 February versus 17 January; P < 0.01). Consequently, seasonal anoestrus was 32 days shorter in does on the higher plane of nutrition (P < 0.01). The seasonality of reproductive activity was confirmed in the OVX does, with reduced LH concentrations during spring and summer, and increased LH concentrations in autumn and winter. There was no effect of nutrition on ovulation rate. These results demonstrate that the female Payoya goat exhibits marked reproductive seasonality which is modulated by nutrition but possibly not ovulation rate.