Monocyte distribution width (MDW) as an infection indicator in severe patients attending in the Emergency Department: a pilot study.

OBJECTIVE: The aim of the present study was to evaluate the diagnostic performance of monocyte distribution width (MDW) as a biomarker for sepsis diagnosis in severe patients attended in the Emergency Department for different conditions and not only infections. METHODS: We performed an observational study in a consecutive prospective cohort including severe patients attending the Emergency Department with different conditions. MDW and other biomarkers were determined from samples obtained during the first care of patients. The diagnostic performance of the different biomarkers was determined based on the final diagnosis at patient discharge. RESULTS: One hundred two patients, with a mean age of 76.7 (SD 16.5) years were included, 53 being (51.9%) male. Among the patients included, 65 (63.7%) had an infectious disease while the remaining had other different conditions. A MDW cut-off of 20.115 provided the best accuracy to identify infected patients, with a sensitivity of 89.2 (95% CI 79.4-94.7), a specificity of 89.2 (95% CI 75.3-95.7), a positive predictive value of 93.5 (95% CI 84.6-97.5), a negative predictive value of 82.5% (95% CI 68.0-91.3), a positive likelihood ratio of 8.25 (3.26-20.91), and a negative likelihood ratio of 0.12 (0.06-0.24). The area under the receiver operating characteristic curve for infection according to MDW was 0.943 (95% CI 0.897-0.989; p<0.001). CONCLUSIONS: A MDW > 20.115 may be associated with infection and could help to distinguish between infected and non-infected patients in severe patients. These results must be confirmed in new studies due to the limited patient sample included.

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin.

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

Dynamics of clinical biomarkers as predictors of immunotherapy benefit in metastatic melanoma patients.

PURPOSE: Baseline LDH, derived neutrophil-lymphocyte ratio (dNLR) and immune-related adverse events (irAEs) are associated with outcomes of patients with metastatic melanoma (MM). We hypothesized whether dynamic shifts in LDH, dNLR and incidence of irAEs may impact the prognosis of MM patients treated with anti-CTLA4 or anti-PD1 as single agents. METHODS: Retrospective analysis of medical charts from MM patients with prospective monitoring of dNLR, LDH values and irAE incidence. Primary endpoint was overall survival (OS). RESULTS: Patients switching from either high dNLR (≥2.5) to low dNLR (HR: 0.14; 0.03-0.74; p = 0.02) or high LDH (≥1.5 × ULN) to low LDH levels (HR: 0.08; 0.01-0.68; p = 0.02) had significantly better OS than those with high dNLR or LDH scores at the end of cycle 2. Longer OS was also observed in patients developing irAEs ≥ grade 2 as compared to no irAEs (HR: 0.2; 0.05-0.89; p = 0.03). CONCLUSIONS: We found that major shifts in dNLR and LDH measures from baseline to cycle 2 measures and shifts from baseline to cycle 2 are significantly associated with OS in MM patients receiving single agent anti-PD1 therapy. Laboratory changes and clinical variables may help optimize prognostic estimates.

Pasteurella multocida isolates associated with ovine pneumonia are toxigenic.

The P. multocida toxin (PMT), a dermonecrotic protein encoded by the toxA gene, is the major virulence factor of capsular type D P. multocida strains causing progressive atrophic rhinitis (PAR) in pigs. A high frequency of P. multocida isolates harboring the toxA gene has been found among ovine pneumonic isolates, although the ability of these isolates to express PMT has never been examined. In this study we have investigated the ability of ovine toxA+ P. multocida isolates (n = 57) to express a functional toxin by detection of PMT toxin antigen using an ELISA test and its cytopathic effect in a Vero cell assay. PMT antigen was expressed in the great majority (54/57; 94.7%) of toxA+ isolates. Moreover, the 100% toxA+ ovine isolates analyzed produced a cytopathic effect in Vero cells within 24-48 h post-inoculation, identical to that described for porcine toxigenic P. multocida isolates. These results show for the first time that, in addition to isolates associated with PAR, isolates of P. multocida associated with pneumonia in sheep are also toxigenic. In addition, we found a total agreement (Kappa = 1; C.I. 0.75-1.25) between the detection of the toxA gene and the toxigenic capability of P. multocida isolates, indicating the PCR detection of toxA would be a suitable predictive marker of the toxigenic fitness of P. multocida.

Use of pepper crop residues for the control of root-knot nematodes.

The biofumigant effect of pepper crop residues (PCR) for controlling Meloidogyne incognita populations was evaluated. Under laboratory conditions, 0, 5, 10 and 20 g PCR were applied to 500 g nematode infested soil, with four replicates per treatment. After 20 days at 25 degrees C, PCR reduced significantly M. incognita populations and root galling indices in susceptible tomato cv. Marmande, and increased K, N and organic C in soil. In the field, biofumigation with PCR combined with fresh animal manures (with and without plastic cover), methyl bromide, and a control were evaluated through root galling indices on a pepper crop. Each treatment, except for the control, had a grafted and non-grafted susceptible pepper sub-treatment, with three replicates. Root galling indices were lower, and yields higher, on grafted plants, biofumigation with PCR and plastic cover, with similar values as MB treatment, suggesting that biofumigation with PCR is an efficient non-chemical alternative to control M. incognita populations, especially when applied with plastic cover, nitrogen-rich organic matter and followed by grafting on resistant pepper.

Alternate-day versus daily energy restriction diets: which is more effective for weight loss? A systematic review and meta-analysis.

BACKGROUND: Alternate-day-fasting (ADF) has been proposed as an effective dieting method. Studies have found that it also can increase life span in rodents, and reduce inflammation in humans. The aim of this paper was to systematically review the efficacy of ADF compared to very-low-calorie dieting (VLCD) in terms of weight loss, and reduction of fat mass and fat-free mass. METHODS: Systematic review: PubMed literature searches were performed. Fixed review procedures were applied. Studies were evaluated for quality. Twenty-eight studies were included. Meta-analysis: 10/28 studies (four ADF and six matched VLCD) were further analyzed. RESULTS: After adjustment for BMI and duration, there was no significant difference in mean body weight loss (VLCD 0.88 kg more weight loss than ADF, 95% CI: -4.32, 2.56) or fat-free mass (VLCD 1.69 kg more fat-free mass loss than ADF, 95% CI: -3.62, 0.23); there was a significant difference observed in fat mass (ADF 3.31 kg more fat mass loss than VLCD, 95% CI: 0.05, 6.56). Meta-analysis showed that, among ADF studies, the pooled change in body weight, fat mass and fat-free mass was 4.30 kg (95% CI: 3.41, 5.20), 4.06 kg (95% CI: 2.99, 5.13) and 0.72 kg (95% CI: -0.07, 1.51), respectively, while among VLCD studies, the pooled change was 6.28 kg (95% CI: 6.08, 6.49), 4.22 kg (95% CI: 3.95, 4.50) and 2.24 kg (95% CI: 1.95, 2.52), respectively. CONCLUSIONS: Our results from both the systematic review and the meta-analysis suggest that ADF is an efficacious dietary method, and may be superior to VLCD for some patients because of ease of compliance, greater fat-mass loss and relative preservation of fat-free mass. Head-to-head randomized clinical trials are needed to further assess relative efficacy of these two approaches.

[Update in Infectious Diseases 2016]. / Actualización en Patología Infecciosa 2016.

Antimicrobial resistance increases it health, social and economic impact. in all areas (state, regional and local), initiatives to try to contain the problem of resistance arise. In the update of this year 2016, we study microbiological, epidemiological and clinical aspects of multi-resistant bacteria, as well as resources for therapeutic approach, from ancient to modern drugs from therapeutic combinations to optimization Stewardship programs. In the case of fungal infection, we analyze clinical scenarios with different species in yeast or new clinical settings in filamentous fungi. Taking paediatric population, homologies and differences with adults in invasive fungal infection were compared. Finally in the field of parasitology, treatment of severe malaria imported or that resistant to antimalarial drugs were reviewed.

Results of surgical treatment of esophageal achalasia. Multicenter retrospective study of 1,856 cases. GEEMO (Groupe Européen Etude Maladies Oesophagéennes) Multicentric Retrospective Study.

A retrospective analysis of 1,856 patients treated by esophageal achalasia in 23 different surgical departments from seven countries is reported. The predominant symptom was dysphagia (100%), pain, vomiting and weight loss (76.1%). The most useful diagnostic methods were: barium meal (85%), manometry (100%), endoscopy (100%) and 99mTc (100%). Conservative treatment (5.45%) was useful in 5.8% only. Dilatation (16.9%) produced amelioration in 65.9%. Thoracotomy was used in 20.9% and middle line laparotomy in 79.2%. Heller esophagomyotomy was performed in 99.52% associated with anterior fundoplasty in 79.8% and postero-lateral (Mark IV) in 9.75%. Most of the patients were controlled through barium meal, esophagoscopy, esophageal manometry, pHmetry and 99mTc ingestion. Good results after Heller's myotomy with anterior fundoplication were 81.7% and poor 7.2%. Recurrence of achalasia was present in 184 patients. A new esophagomyotomy was performed on 58.6% and distal esophageal resection in 62 (35.3%). In total, 988 patients were reviewed once a year. Absence of gastroesophageal reflux was shown in 73.9% of the explored patients.

[Nutritional management of radiation-induced enteritis: apropos of a case]. / Manejo nutricional en la enteritis rádica: a propósito de un caso.

We present a case of a 46-year-old woman who is hospitalized in March of 1997 for a picture of severe mixed malnutrition. We describe the clinical history since the diagnosis of an endometrium carcinoma in 1995, treated with radiation therapy, with the aim of determining the etiology of the severe malnutrition picture, as well as the different complications she presented in the course of her hospitalization that justify the decisions made in the choice of the nutritional support.

[Prevalence and costs of chronicity and multimorbidity in the population covered by the Basque public telecare service]. / Prevalencia de cronicidad y multimorbilidad en la población cubierta por el servicio público de teleasistencia de Euskadi: impacto en costes y calidad.

BACKGROUND: The public telecare service in the Basque Autonomous Community (betiON) is a service offered by the Department of Employment and Social Policy of the Basque Government and offers telephone support to elderly and disabled populations, providing communication with an assistance centre. This connection with health care devices makes it possible to implement shared information systems with health and social data, which enable a characterization of the population attended to and the development of integrated models for health and social provision. OBJECTIVE: To describe the distribution of chronic diseases and multimorbidity among users of betiON, to estimate the cost of their health care and to compare these indicators with those of the general population. METHODS: We extracted information from betiON and public healthcare databases. We characterized the telecare population above 65 years (N = 23.742) and compared it with the total population in the Basque Autonomous Community (N = 2.262.707) with respect to variables in demography socio-economic burden, costs and ambulatory care conditions. RESULTS: In the telecare population, the average age is 83 years, 80% are women, 55.1% live alone and reside in poorer neighbourhoods. Forty-two point five per cent of males and 36.5% of women are affected by five or more chronic conditions, averaging 4.06 pathologies per person. They also show higher healthcare costs than the general population. CONCLUSIONS: Telecare users have a higher disease burden, greater need for healthcare and unfavourable social conditions. Telecare provides an opportunity for innovation and intervention, through the coordination of social and healthcare services.

Cardiotoxicity of tyrosine-kinase-targeting drugs.

The development of the so-called "targeted therapies", particularly those drugs that inhibit the activity of tyrosine kinases, has become a remarkable progress in the treatment of neoplastic diseases. The small molecule tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of chronic myeloid leukemia, and trastuzumab, the humanized monoclonal antibody against the ERBB2 receptor tyrosine kinase, has proved to have a high efficacy in 25% of breast cancers. On the basis of treatment success it is expected that targeted therapies will spread its use in the future. Recent data has shown that some of these therapies are associated with certain cardiotoxicity ranging from asymptomatic mild left ventricular dysfunction to congestive heart failure through different mechanisms. However, rates of cardiotoxicity associated with TKI are not well known mainly because clinical trials usually do not include predefined cardiac endpoints or the assessment of left ventricular function before and during treatment. In addition, it is especially difficult to diagnose heart failure in patients with some kinds of cancer who have many reasons to develop dyspnoea. Here we summarize what is known up to date about the cardiotoxicity of drugs targeting the tyrosine kinases. Being aware of the risk of using these drugs is particularly important to early detect and institute the appropriate treatment to prevent irreversible myocardial injury, especially when some neoplastic diseases, as haematological or breast cancers, can affect to young people with an estimated long-term survival.

EURRECA: development of tools to improve the alignment of micronutrient recommendations.

Approaches through which reference values for micronutrients are derived, as well as the reference values themselves, vary considerably across countries. Harmonisation is needed to improve nutrition policy and public health strategies. The EURRECA (EURopean micronutrient RECommendations Aligned, http://www.eurreca.org) Network of Excellence is developing generic tools for systematically establishing and updating micronutrient reference values or recommendations. Different types of instruments (including best practice guidelines, interlinked web pages, online databases and decision trees) have been identified. The first set of instruments is for training purposes and includes mainly interactive digital learning materials. The second set of instruments comprises collection and interlinkage of diverse information sources that have widely varying contents and purposes. In general, these sources are collections of existing information. The purpose of the majority of these information sources is to provide guidance on best practice for use in a wider scientific community or for users and stakeholders of reference values. The third set of instruments includes decision trees and frameworks. The purpose of these tools is to guide non-scientists in decision making based on scientific evidence. This platform of instruments will, in particular in Central and Eastern European countries, contribute to future capacity-building development in nutrition. The use of these tools by the scientific community, the European Food Safety Authority, bodies responsible for setting national nutrient requirements and others should ultimately help to align nutrient-based recommendations across Europe. Therefore, EURRECA can contribute towards nutrition policy development and public health strategies.

Prevalence of Cryptosporidium spp. in asymptomatic sheep in family flocks from Mexico State.

To determine Cryptosporidium spp. prevalence in faeces from asymptomatic sheep, 37 family flocks in Mexico State were sampled. Data were collected by the interview method and Ziehl-Neelsen stain of faecal samples for Cryptosporidium identification. The independent group proportion hypothesis test was used for differences in prevalences between sheep farms. A 34.3% general prevalence was found, and prevalence in herds with >100 animals was significantly higher (40.6%). Correlation was found between flock size and Cryptosporidium spp. presence (odds ratio, OR, 2.57; confidence interval, IC(95%), 1.84-3.60).

[The complications of transurethral operations (an analysis of 5-year results)]. / Oslozhneniia transuretral'nykh operatsii (analiz 5-letnikh rezul'tatov).

Based on analysis of 309 transurethral [correction of transureteral] surgeries performed on patients with various diseases (prostatic adenoma, prostatic carcinoma, vesical tumors, urethral stenosis, cervical sclerosis) the authors scrutinized various complications: intraoperative (hemorrhages, vesical perforations) and postoperative ones. The most common postoperative complications were acute pyelonephritis, (5.82 per cent), dysuria (3.88), urethral stenosis (2.91 per cent). Immediate and long-term postsurgical hemorrhages were documented in 4.2 per cent and enuresis in 1.94 per cent of the patients. Certain prophylactic measures were considered. The duration of surgery was found to be correlated with the incidence of postoperative complications and it should not exceed 30-49 min. The mortality rate was 1.29 per cent.

Pancreato-biliary-duodenal interposition of isolated jejunal loop in the surgical treatment of selected cases of chronic pancreatitis.

Eight patients suffering from symptoms of chronic pancreatitis with dilation of Wirsung's and common bile ducts were selected for a double biliary and pancreatic diversion by interposition of two jejunal loops between these ducts and the duodenum. In three patients a single loop was used, performing an anastomosis on the proximal end to the Wirsung duct about 45 centimeters below the anastomosis between the common duct and the jejunum. The distal end of this loop was anastomosed end-to-side to the duodenum. In five patients two different jejunal loop were used. While the proximal end of one loop was anastomosed to the Wirsung duct, the proximal end of the second loop was anastomosed to the common bile duct. End-to-side anastomosis was then performed between the distal end of both loops and the duodenum. There were no deaths or serious complications. The minimum follow-up was twelve months and the maximum three and half years, all the patients being without symptoms and with normalization of the laboratory tests three months after operation.