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.

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.

Effect of in-hospital glycemic variability on mortality in patients with diabetes. / Efecto de la variabilidad glucémica intrahospitalaria en la mortalidad de los pacientes con diabetes.

INTRODUCTION: The aim of this study was to evaluate the impact of mean blood glucose (MBG) and glycaemic variability (GV) during hospitalisation on mortality after discharge. MATERIAL AND METHODS: We conducted a retrospective longitudinal analytical cohort study that included patients discharged form a department of internal medicine with a diabetes-related diagnosis The evaluated prognosis was mortality. During hospitalisation, the patients' clinical, laboratory and glycaemic control-related variables were recorded (MBG, GV and hypoglycaemia). The GV was measured with the coefficient of variation (CV). We calculated the mortality rates for every 1000 patient-years and compared them with Kaplan-Meier curves. We determined the predictors of mortality by performing a Cox regression. RESULTS: The study included 276 patients with a mean age of 77.6 (SD, 10.2) years. The median outpatient follow-up duration was 2.7 years. In the multivariate analysis, an MBG >140mg/dl (HR, 1.72; 95% CI 1.14-2.61; p=.01) and a CV >0.29 (HR, 1.52; 95% CI 1.12-2.06; p=.006) but not the presence of hypoglycaemia were additively and independently associated with an increased risk of mortality. An MBG >140mg/dl with a CV >0.29 increased the mortality rates (123 vs. 317 per 1000 patient-year; p <.001) and the adjusted mortality risk (HR, 2.70; 95% CI 1.71-4.27; p<.001) compared with having an MBG ≤140mg/dl. CONCLUSION: The simultaneous presence of a high MBG level and CV constitutes a powerful tool for stratifying mortality risk after hospital discharge.

[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.

Embryological and comparative description of the cephalic vein joining the external jugular vein: A case report.

The cephalic vein arises from the radial end of the dorsal venous arch. It turns around the radial border of the forearm and passes proximally along the arm to the shoulder, where it enters the axillary vein by penetrating the clavipectoral triangle. The cephalic vein is prone to vary at the antecubital fossa, where it forms numerous anastomoses. A male cadaver fixated with a 10% formalin solution was dissected during regular anatomy lessons. It was found that the cephalic vein crossed the upper third of the arm between two fasciculi of the deltoid muscle and reached the shoulder, where it passed above the acromion and crossed the posterior border of the clavicle in order to join the external jugular vein. The cephalic vein is one of the most used veins for innumerous activities, such as venipunctures and arteriovenous fistula creation. Furthermore, it is an anatomical landmark known for its consistent anatomy, as it possesses low rates of variability. Despite that, its anatomical variations are clinically and surgically significant and healthcare professionals must be aware of the variations of this vessel. We aim to report a rarely described variation of the cephalic vein and discuss its embryological, phylogenetic and clinical features.

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.

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.

Are WWTPs effluents responsible for acute toxicity? Seasonal variations of sediment quality at the Bay of Cádiz (SW, Spain).

Adverse effects of wastewater treatment plants (WWTPs) on sediment quality at the Bay of Cádiz (SW, Spain) were evaluated by a battery of acute bioassays and chemical contamination. Five sites directly affected by WWTPs effluents and one control site were chosen. Results evidenced clear deterioration of ecological sediment quality parameters and possible effects on aquatic communities towards WWTPs areas. Acute toxicity and chemical contamination varied significantly across the studied sites and differed between winter and summer seasons. The Bay of Cádiz is contaminated by PAHs, metals, detergents (SAS) and pharmaceutical products. Principal Component Analyses indicated metals, SAS and pharmaceutical products as the major environmental stresses. Sea-urchin embryo-larval and microalgae growth rate were the most sensitive bioassays to evaluate resuspension of contaminants (elutriate) from bulk sediment. Amphipods mortality and Microtox(®) solid phase test bioassays were recommended to evaluate bulk sediment quality. Therefore, the use of multiple-bioassays, sensitive to sediment pollution, may provide complementary information to diagnose environmental factors that can impair aquatic communities. The battery of bioassays is recommended to assess and monitor marine sediments directly affected by a mixture of contaminants released from WWTPs.

Effects of 6 Weeks of Balance Training on Chronic Ankle Instability in Athletes: A Randomized Controlled Trial.

The objective of the present study was to determine the effectiveness of a 6-week balance training program on patients with Chronic Ankle Instability (CAI) in relation to the results obtained in Dynamic Balance, subjective feeling of instability and pain using a single-blind randomized controlled trial. 70 athletes were randomly assigned to control or intervention group. The control group performed their usual training, and the intervention group was administered the same usual activity in addition to a balance program. The paired t-test was performed to evaluate the change scores in each group. The t-test for independent samples was performed to evaluate between-group differences in change scores. Significance level was assigned for p-values less than 0.05 for all analyses. There were significant differences between groups in change scores in CAIT and all of the SEBTs reach distances (p<0.001) but not in Pain (p=0.586). The effect sizes were larger for the outcomes measures that showed significant differences. In the within-group change, the experimental groups showed larger effect sizes in CAIT, SEBT posteromedial and SEBT posterolateral, and moderate effect sizes in SEBT anterior. Exercise therapy training based on multi-station balance tasks led to significant improvements in dynamic balance and self-reported sensation of instability in patients with CAI.

Molecularly imprinted polymer for selective determination of Δ9-tetrahydrocannabinol and 11-nor-Δ9-tetrahydrocannabinol carboxylic acid using LC-MS/MS in urine and oral fluid.

The use of molecularly imprinted polymers (MIPs) for solid phase extraction (MISPE) allows a rapid and selective extraction compared with traditional methods. Determination of Δ(9)-tetrahydrocannabinol (THC) and 11-nor-Δ(9)-tetrahydrocannabinol carboxylic acid (THC-COOH) in oral fluid (OF) and urine was performed using homemade MISPEs for sample clean-up and liquid chromatography tandem mass spectrometry (LC-MS/MS). Cylindrical MISPE shaped pills were synthesized using catechin as a mimic template. MISPEs were added to 0.5 mL OF or urine sample and sonicated 30 min for adsorption of analytes. For desorption, the MISPE was transfered to a clean tube, and sonicated for 15 min with 2 mL acetone:acetonitrile (3:1, v/v). The elution solvent was evaporated and reconstituted in mobile phase. Chromatographic separation was performed using a SunFire C18 (2.5 µm; 2.1 × 20 mm) column, and formic acid 0.1% and acetonitrile as mobile phase, with a total run time of 5 min. The method was fully validated including selectivity (no endogenous or exogenous interferences), linearity (1-500 ng/mL in OF, and 2.5-500 ng/mL in urine), limit of detection (0.75 and 1 ng/mL in OF and urine, respectively), imprecision (%CV <12.3%), accuracy (98.2-107.0% of target), extraction recovery (15.9-53.5%), process efficiency (10.1-46.2%), and matrix effect (<-55%). Analytes were stable for 72 h in the autosampler. Dilution 1:10 was assured in OF, and Quantisal™ matrix effect showed ion suppression (<-80.4%). The method was applied to the analysis of 20 OF and 11 urine specimens. This is the first method for determination of THC and THC-COOH in OF using MISPE technology.

Cross-cultural adaptation and psychometric evaluation of the Spanish version of the Knowledge and Attitudes of Pain questionnaire (KNAP) in physiotherapists.

BACKGROUND: Healthcare providers' attitudes and beliefs can influence how patients with persistent musculoskeletal pain are treated. A biopsychosocial approach is more effective than a purely biomedical approach. Ensuring healthcare professionals have appropriate pain science education (PSE) is essential for successful treatment outcomes. OBJECTIVE: To validate the Spanish version of the Knowledge and Attitudes of Pain (KNAP-SP) questionnaire among Spanish physiotherapists and students and analyze its psychometric properties. METHODS: From May to October 2022, two independent teams adapted the KNAP questionnaire from English to both European and Hispanic-Spanish. A cross-sectional validation study was conducted with 517 physiotherapists examining internal consistency (Cronbach's alpha), structural validity (exploratory factor analysis), and construct validity (hypothesis testing). Longitudinal analyses assessed test-retest reliability (intraclass correlation coefficient [ICC2,1; n = 63]) and responsiveness following a PSE intervention using Receiver Operating Characteristic (ROC) curve analysis and hypothesis testing (n = 70). RESULTS: The KNAP-SP showed strong internal consistency [overall α coefficient = 0.86; domain 1 (α = 0.82); domain 2 (α = 0.70)], explaining 32.3% of the variance. Construct validity was supported by 75% of the hypotheses. Test-retest reliability was high (ICC2,1 = 0.84). KNAP-SP's responsiveness was confirmed by ROC analysis (area under the curve [AUC] = 0.87 [95% CI: 0.79-0.96, p-value <.01]) and accepting 75% of prior hypotheses. The minimal clinically important change was 6.96 points. No floor or ceiling effects were detected. CONCLUSIONS: The KNAP-SP, with robust psychometric properties and successful adaptation and validation, is a valuable tool for assessing pain knowledge and attitudes among Spanish-speaking physiotherapists.

[Cutaneous tuberculosis in an area of Mallorca (2003-2011)]. / Tuberculosis cutánea en una zona de Mallorca (2003-2011).

BACKGROUND AND OBJECTIVE: Tuberculosis is an important health care problem, even in our setting. The objective of this study is to describe clinic and epidemiological features of cutaneous tuberculosis in our area. PATIENTS AND METHODS: A retrospective study was performed of all patients diagnosed of cutaneous tuberculosis in a hospital in Mallorca (Spain) from January 2003 to July 2011. The clinical forms, diagnostic methods used, treatment used and clinical course were recorded. RESULTS: Twenty-eight cases of cutaneous tuberculosis were diagnosed (5.9% of the tuberculosis cases diagnosed in this period), 15 with classic cutaneous tuberculosis (14 scrofuloderma, 1 empyema necessitatis) and 13 patients with tuberculids (8 erythema induratum of Bazin disease and 5 erythema nodosum). Scrofulodermas came from lymph nodes in 10 of the patients, infected bone in 4 and pleural in one case; 13/28 patients came from other continents. Most of the patients were treatment with 3-4 tuberculostatic drugs, with favorable course. CONCLUSIONS: Cutaneous tuberculosis is not uncommon in our setting. In classic cutaneous tuberculosis culture is the gold standard diagnostic method while tuberculids are most commonly diagnosed by histology.

Cytomegalovirus ileitis in an immunocompetent patient.

Cytomegalovirus (CMV) is a virus that belongs to the family of Herpesviridae. Infection can cause a serious disease in immunocompromised patients, but it can also affect immunocompetent patients, creating generally self limiting symptoms. However, in some cases it can be fatal. We present a case of CMV ileitis with serious clinical symptoms that led to an operation in an immunocompetent patient.

Effect of in-hospital glycemic variability on mortality in patients with diabetes.

INTRODUCTION: The aim of this study was to evaluate the impact of mean blood glucose (MBG) and glycaemic variability (GV) during hospitalisation on mortality after discharge. MATERIAL AND METHODS: We conducted a retrospective longitudinal analytical cohort study that included patients discharged form a department of internal medicine with a diabetes-related diagnosis. The evaluated prognosis was mortality. During hospitalisation, the patients' clinical, laboratory and glycaemic control-related variables were recorded (MBG, GV and hypoglycaemia). The GV was measured with the coefficient of variation (CV). We calculated the mortality rates for every 1000 patient-years and compared them with Kaplan-Meier curves. We determined the predictors of mortality by performing a Cox regression. RESULTS: The study included 276 patients with a mean age of 77.6 (SD, 10.2) years. The median outpatient follow-up duration was 2.7 years. In the multivariate analysis, an MBG > 140 mg/dL (HR = 1.72; 95% CI 1.14-2.61; p = .01) and a CV > 0.29 (HR = 1.52; 95% CI 1.12-2.06; p = .006), but not the presence of hypoglycaemia, were additively and independently associated with an increased risk of mortality. An MG > 140 mg/dL with a CV > 0.29 increased the mortality rates (123 vs. 317 per 1000 patient-year; p < .001) and the adjusted mortality risk (HR = 2.70; 95% CI 1.71-4.27; p < .001) compared with having an MBG ≤ 140 mg/dL. CONCLUSION: The simultaneous presence of a high MBG level and CV constitutes a powerful tool for stratifying mortality risk after hospital discharge.

Low-energy short-term cold atmospheric plasma: Controlling the inactivation efficacy of bacterial spores in powders.

The present research work aims to elucidate kinetics and mechanisms of the inactivation of Bacillus subtilis spores by a surface micro-discharge (SMD) - cold atmospheric pressure plasma (CAPP). Regarding industrial applications, the inactivation of spores was also studied for a static layer of a biopolymer powder or film, with an air plasma and at ambient pressure. Close to 4 log10 cycles of inactivation of Bacillus subtilis spores were achieved when exposing spores on flat glass to the SMD-CAPP. This effect can be reached at a very low plasma power density of 5 mW/cm2 in 7 min exposure time. The maximum inactivation level of spores drops when treating corn-starch powder to 2.6 log10 cycles at 7 mW/cm2 plasma power density for 5 min and with a polymer load of 5 mg/cm2. Similar is true for films produced with hydroxymethyl cellulose (HMC). The inactivation efficacy can be tuned and is a function of applied surface energy (product of the plasma power density and the exposure time) and the polymer load. Plasma diagnostics reveal the fundamental importance of reactive nitrogen species (RNS) in the inactivation. Etching of spore hull is supposed to be triggered by the plasma density, while UV-C and UV-B radiation do not contribute directly and significantly to the inactivation effect at least in a biopolymer matrix. Fluidization of a fixed powder layer is supposed to overcome limitations of the inactivation efficacy by reducing the diffusion distance of active plasma species between the source and the sample. The combination of low plasma power density with short treatment time is supposed to reduce the risk of the formation of side-products from the matrix.

Effects of season and feeding level on reproductive activity and semen quality in Payoya buck goats.

The aim of this study was to determine if there is a seasonal pattern of reproductive activity in male Payoya goats and if this seasonality can be modulated by a higher level of nutrition. For a period of 16 months, 10 adult bucks were divided into two experimental groups that differed in their feeding level. The high nutrition group (H, n=5) received 1.6 times their maintenance food requirements. The control nutrition group (C, n=5) received a diet that supported 1.1 times their maintenance requirements. Body weight and testosterone concentrations were determined weekly, and testicular weight was determined every 2 weeks. Sexual behaviour and semen characteristics were determined monthly. Feeding level did not affect the onset or the end of the reproductive activity as measured by testosterone concentrations, with high testosterone concentrations between July and November. Ejaculation latency was positively influenced by feeding level: 43.2+/-2.2s vs. 61.6+/-3.2s for H and C group, respectively (P<0.001). The percentage of males that ejaculated or that were sexually active was higher in the H group (P<0.01). No differences between feeding levels were observed in the different semen characteristics studied. However, major differences between months were observed for all studied variables. These results lead us to conclude that Payoya bucks exhibit large seasonal variation in their reproductive activity. Higher feeding level allowed a better sexual behaviour in bucks in late spring, when male effect is used on the local livestock to breed females.

[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.

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.

Microbial indicators of faecal contamination in waters and sediments of beach bathing zones.

This study presents the results obtained of the microbial characterization of waters and sediments of 18 coastal bathing zones of the south-western coast of the Iberian Peninsula. To make this characterization, two indicators of faecal contamination have been selected: faecal coliforms (FC) and Clostridium perfringens (CP). The results show that low concentrations of FC and CP in water not necessarily implies that their concentration in sediment and elutriates has to be low as well. The highest concentrations were found in locations close to the mouth of rivers, and in beaches of low energy and hence low water renewal, and high accumulation of fine sediments. The concentrations of FC were lower than those obtained for CP in most of the sampling locations. Although quality standards for bathing waters do not take the parameter CP into account, it has been demonstrated that it should be a good indicator of faecal contamination.