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ContextRelapse and recurrence rates of pressure injuries (PIs) are very high in spinal cord injured patients. That is the reason why alternative therapies, such the stem cells derived from bone marrow, have been developed.ObjectiveTo compare this new technique of infiltration-infusion of mononuclear cells from bone marrow with conventional surgery.DesignA retrospective study was carried out in patients with spinal cord injuries who had PIs, category III/IV, in the pelvic area, during a 14-year follow-up period.SettingOne group was treated with conventional surgery and, in the other group, mononuclear cells were infused.ParticipantsOne hundred and forty-nine patients were registered, 63 (42.3%) in the conventional surgery group and 86 (57.7%) in the mononuclear cell group.ResultsA comparative study between these 2 groups was carried out. There were no significant differences in ulcer healing in the first 6 months, but 6 months and one-year post-treatment, they were found. At 6 months, no patient in the conventional surgery group showed dehiscence or fistulization of the wound and, one year after surgery, only 3.17% recurred in the conventional group. In addition, there was a statistically significant relationship between days of hospitalization and the type of bacterial contamination and the intervention group.ConclusionBone marrow mononuclear cell infusion-infiltration is an alternative treatment for PIs and fistula during the first 6 months, instead of conventional surgery. However, in the medium-long term, conventional surgery is more effective.

Aim:T2Bacteria®Panel detects six ESKAPE pathogens in around 3.5 h directly in whole blood. Our aim was to compare T2Bacteria with simultaneous blood culture in critically ill children with suspected bloodstream infection. Materials & methods:Retrospective study of critically ill children admitted to our tertiary-care center (2018–2020). Results:A total of 60 patients were recruited, including 63 episodes and 75 T2Bacteria/blood cultures were performed. Overall agreement between T2Bacteria and blood culture was 78.7% with a discordance of 21.3% (16/75 samples). Conclusion:T2Bacteria Panel may be useful in critically ill children providing an accurate and fast diagnosis of bacteremia directly from blood sample and detecting pathogens not recovered in blood cultures.

ObjectiveTo analyse ocular and systemic findings of patients presenting with systemic metastasis.Methods and analysisIt is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases.ResultsOf 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1–T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category.ConclusionsThough higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.

AbstractPurposeThe aim of our study was to analyse the short-term prognostic value of different biomarkers in patients with COVID-19.MethodsWe included patients admitted to emergency department with COVID-19 and available concentrations of cardiac troponin I (cTnI), D-dimer, C-reactive protein (CRP) and lactate dehydrogenase (LDH). Patients were classified for each biomarker into two groups (low vs. high concentrations) according to their best cut-off point, and 30-day all-cause death was evaluated.ResultsAfter multivariate adjustment, cTnI ≥21 ng/L, D-dimer ≥1112 ng/mL, CRP ≥10 mg/dL and LDH ≥334 U/L at admission were associated with an increased risk of 30-day all-cause death (hazard ratio (HR) 4.30; 95% CI 1.74–10.58; p = 0.002; HR 3.35; 95% CI 1.58–7.13; p = 0.002; HR 2.25; 95% CI 1.13–4.50; p = 0.021; HR 2.00; 95% CI 1.04–3.84; p = 0.039, respectively). The area under the curve for cTnI was 0.825 (95% CI 0.759–0.892) and, in comparison, was significantly better than CRP (0.685; 95% CI 0.600–0.770; p = 0.009) and LDH (0.643; 95% CI 0.534–0.753; p = 0.006) but non-significantly better than D-dimer (0.756; 95% CI 0.674–0.837; p = 0.115).ConclusionsIn patients with COVID-19, increased concentrations of cTnI, D-dimer, CRP and LDH are associated with short-term mortality. Of these, cTnI provides better mortality risk prediction. However, differences with D-dimer were non-significant.

La elevación de la troponina cardiaca como marcador de daño miocárdico es un predictor pronóstico en pacientes con COVID-19. Sin embargo, se desconoce su rendimiento en pacientes coetáneos con sospecha de COVID-19 pero con prueba de reacción en cadena de la polimerasa negativa.

Ustekinumab (UST) es un anticuerpo monoclonal frente a IL-12/23 aprobado en España (2017) para tratar el brote moderado/grave de enfermedad de Crohn.

CT-P13 es un fármaco biosimilar de infliximab (IFX), efectivo en pacientes con enfermedad inflamatoria intestinal (EII). La medición de niveles de IFX y anticuerpos anti-IFX forma parte del tratamiento integral de dicha enfermedad.

The management of patients with an incidentally detected pancreatic cyst is a significant clinical challenge. More than 80% are detected as incidental findings on CT scan or MRI. A case is presented of a 41-year-old patient with an asymptomatic pancreatic cyst which was detected during a check-up.

Pepper constitutes an important source of (poly)phenols, mainly flavonoids. Nevertheless, heat treatments applied prior to consumption may have an impact on these antioxidants, and thus may also affect their potential bioactivity. In this study, the effect of industrial and culinary treatments on the total and individual (poly)phenolic content of Piquillo pepper (Capsicum annuumcv. Piquillo) was thoroughly evaluated by high-performance liquid chromatography coupled to tandem mass spectrometry. A total of 40 (poly)phenols were identified and quantified in raw pepper. Flavonoids (10 flavonols, 15 flavones, and 2 flavanones) were the major compounds identified (62.6%). Among the 13 phenolic acids identified in raw samples, cinnamic acids were the most representative. High temperatures applied and subsequent peeling during industrial grilling drastically decreased the total (poly)phenolic content from 2736.34 to 1099.38 μg/g dm (59.8% reduction). In particular, flavonoids showed a higher reduction of 87.2% after grilling compared to nonflavonoids which only decreased by 14%. Moreover, 9 nonflavonoids were generated during grilling, modifying the (poly)phenolic profile. After culinary treatments, specifically frying, (poly)phenols appear to be better released from the food matrix, enhancing their extractability. Overall, industrial and culinary treatments differently affect both the total and individual (poly)phenolic compounds of pepper and, despite the reduction, they might also positively influence their bioaccessibility.

Intravitreal dexamethasone implant is a useful treatment for radiation maculopathy secondary to plaque brachytherapy in choroidal melanoma. A decrease in foveal thickness was demonstrated during the follow-up of patients.

The controlled branching process (CBP) is a generalization of the classical Bienaymé–Galton–Watson branching process, and, in the terminology of population dynamics, is used to describe the evolution of populations in which a control of the population size at each generation is needed. In this work, we deal with the problem of estimating the offspring distribution and its main parameters for a CBP with a deterministic control function assuming that the only observable data are the total number of individuals in each generation. We tackle the problem from a Bayesian perspective in a non parametric context. We consider a Markov chain Monte Carlo (MCMC) method, in particular the Gibbs sampler and approximate Bayesian computation (ABC) methodology. The first is a data imputation method and the second relies on numerical simulations. Through a simulated experiment we evaluate the accuracy of the MCMC and ABC techniques and compare their performances.The controlled branching process (CBP) is a generalization of the classical Bienaymé–Galton–Watson branching process, and, in the terminology of population dynamics, is used to describe the evolution of populations in which a control of the population size at each generation is needed. In this work, we deal with the problem of estimating the offspring distribution and its main parameters for a CBP with a deterministic control function assuming that the only observable data are the total number of individuals in each generation. We tackle the problem from a Bayesian perspective in a non parametric context. We consider a Markov chain Monte Carlo (MCMC) method, in particular the Gibbs sampler and approximate Bayesian computation (ABC) methodology. The first is a data imputation method and the second relies on numerical simulations. Through a simulated experiment we evaluate the accuracy of the MCMC and ABC techniques and compare their performances.

AbstractAdult Polycystic Kidney Disease (APKD) is a single-gene autosomal dominant genetic disorder leading to end-stage renal disease (ESRD, meaning kidney failure). It is associated with mutations in either of two genes, APKD1 and APKD2, and although diagnosis is still mostly by ultrasonography rather than DNA-based tests, this may change in the future. Recent studies have shown that the rates of onset of ESRD associated with APKD1 mutations are much greater than those associated with APKD2 mutations, a form of genetic heterogeneity that differs from, for example, familial breast cancer. In this paper we model the the impact of mutations in APKD1 or APKD2 on critical illness insurance, extending the work of Gutiérrez and Macdonald (2003), which was based on studies predating DNA-based tests. We then extend the model to life insurance and show that the financial impact is strongly dependent on the availability of treatment (dialysis and transplant), but that if it is available, extra premiums for life insurance are modest. We show that genetic heterogeneity introduces a novel problem, because carrying an APKD2 mutation is less risky than having a family history of APKD. Thus, in jurisdictions where family history may be used in underwriting but genetic tests may not, it may be illegal to use knowledge that benefits the applicant.

Previous studies indicate that the carboxyl terminal of connexin43 (Cx43CT) is involved in fast transjunctional voltage gating. Separate studies support the notion of an intramolecular association between Cx43CT and a region of the cytoplasmic loop (amino acids 119–144; referred to as “L2”). Structural analysis of L2 shows two α-helical domains, each with a histidine residue in its sequence (H126 and H142). Here, we determined the effect of H142 replacement by lysine, alanine, and glutamate on the voltage gating of Cx43 channels. Mutation H142E led to a significant reduction in the frequency of occurrence of the residual state and a prolongation of dwell open time. Macroscopically, there was a large reduction in the fast component of voltage gating. These results resembled those observed for a mutant lacking the carboxyl terminal (CT) domain. NMR experiments showed that mutation H142E significantly decreased the Cx43CT-L2 interaction and disrupted the secondary structure of L2. Overall, our data support the hypothesis that fast voltage gating involves an intramolecular particle-receptor interaction between CT and L2. Some of the structural constrains of fast voltage gating may be shared with those involved in the chemical gating of Cx43.

Objective: To evaluate interactions among leptin, adiponectin, resistin, ghrelin, and proinflammatory cytokines [tumor necrosis factor receptors (TNFRs), interleukin‐6 (IL‐6)] in nonmorbid and morbid obesity. Research Methods and Procedures: We measured these hormones by immunoenzyme or radiometric assays in 117 nonmorbid and 57 morbidly obese patients, and in a subgroup of 34 morbidly obese patients before and 6 months after gastric bypass surgery. Insulin resistance by homeostasis model assessment, lipid profile, and anthropometrical measurements were also performed in all patients. Results: Average plasma lipids in morbidly obese patients were elevated. IL‐6, leptin, adiponectin, and resistin were increased and ghrelin was decreased in morbidly obese compared with nonmorbidly obese subjects. After adjusting for age, gender, and BMI in nonmorbidly obese, adiponectin was positively associated with HDLc and gender and negatively with weight (β = −0.38, p< 0.001). Leptin and resistin correlated positively with soluble tumor necrosis factor receptor (sTNFR) 1 (β = 0.24, p= 0.01 and β = 0.28, p= 0.007). In the morbidly obese patients, resistin and ghrelin were positively associated with sTNFR2 (β = 0.39, p= 0.008 and β = 0.39, p= 0.01). In the surgically treated morbidly obese group, body weight decreased significantly and was best predicted by resistin concentrations before surgery (β = 0.45, p= 0.024). Plasma lipids, insulin resistance, leptin, sTNFR1, and IL‐6 decreased and adiponectin and ghrelin increased significantly. Insulin resistance improved after weight loss and correlated with high adiponectin levels. Discussion: TNFα receptors were involved in the regulatory endocrine system of body adiposity independently of leptin and resistin axis in nonmorbidly obese patients. Our results suggest coordinated roles of adiponectin, resistin, and ghrelin in the modulation of the obesity proinflammatory environment and that resistin levels before surgery treatment are predictive of the extent of weight loss after bypass surgery.

Surface antigen negative hepatitis B virus (HBV) infection was evaluated in Venezuela, by molecular characterization of blood samples positive for antibodies to core antigen (anti‐HBc) and negative for surface antigen (HBsAg) in blood donors (residual infections). HBV DNA was found in 11/258 samples (4.3%), and was significantly associated with high levels of anti‐HBc antibodies (>25 UI/ml, P< 0.05), while no correlation was found between the presence of HBV DNA and the levels of anti‐HBs. Synonymous and non‐synonymous mutations were found in the HBV surface region (but not vaccine escape mutants) and in the precore/core region (precore mutants in 2/7 samples and 33–45 bp deletions near the N‐terminal core region in 4/19 samples). While HBV genotype F prevails among HBsAg positive samples from blood donors in Venezuela, residual infection isolates were mainly genotypes A and D. Phylogenetic analysis of viral surface and core region revealed discrepancies in genotype designation in 6/9 samples, suggesting the presence of mixed infection or recombination. In conclusion, HBV residual infection in Venezuela does not seem to be frequently observed in HBV genotype F. This type of infection is frequently associated with variants exhibiting mutations in the surface gene that might be affecting the correct recognition by commercial tests, with precore mutants and with core internal deletions. These variants do not seem to cause severe liver disease, and on the contrary, were found circulating at low viremia. J. Med. Virol. 73:200–207, 2004. © 2004 Wiley‐Liss, Inc.

Obesity is a complex disease associated with insulin resistance. Leptin and the TNF-α system could be involved in the pathogenesis of obesity and insulin resistance. Gastric bypass (GBP) is a surgical treatment for morbidly obese patients. We conducted a study after GBP to analyze the pattern of variation of anthropometric and body composition variables, leptin and sTNFR1 and 2. Methods: 29 morbidly obese women were studied, at baseline and throughout 6 months after gastric bypass. Results: At baseline, the BMI was 49 � 6 kg/m2 and patients showed a higher fasting insulin resistance index (FIRI), leptin, leptin/fat mass and sTNFR1 and 2 than did controls. 6 months after GBP, BMI was 35�4, and FIRI, leptin and leptin/fat mass decreased significantly in the first months and throughout the follow-up. sTNFR1 and 2 showed an initial increase, but at 6 months their concentrations were similar to baseline (2.6�0.8 vs 3.1�0.95 ng/ml, P < 0.05; 4.6�1.4 vs 7�2.5 ng/ml, P < 0.05). At baseline, there was no correlation between leptin and BMI and body composition variables but there was a correlation with fat mass (r=0.42, P=0.004) and sTNFR1 (r=0.58, P=0.001). At 6 months, there was a correlation between leptin and BMI (r=0.53, P=0.004) and sTNFR1 (r=0.46, P=0.013). Conclusions: Morbidly obese women after GBP became less insulin resistant with lower leptin concentrations, but showed an initial increase of sTNFR1 and 2. This pattern of variation of the leptin TNF-α axis suggests a disregulation of the system after dramatic weight loss and also that insulin and leptin up-regulate TNF-α production irrespective of insulin resistance status.

AbstractAdult polycystic kidney disease (APKD) is a single-gene autosomal dominant genetic disorder leading to end-stage renal disease (ESRD, meaning kidney failure). It is associated with mutations in at least two genes, APKD1 and APKD2, but diagnosis is mostly by ultrasonography. We propose a model for critical illness (CI) insurance and estimate rates of onset of ESRD from APKD using two studies. Other events leading to claims under CI policies are included in the model, which we use to study (a) extra premiums under CI policies if the presence of an APKD mutation is known, and (b) the possible costs arising from adverse selection if this information is unavailable to insurers. The extra premiums are typically very high, but because APKD is rare, the possible cost of adverse selection is low. However, APKD is just one of a significant number of single-gene disorders, and this benign conclusion cannot be assumed to apply to all genetic disorders taken together. Moreover, ignoring known genetic risks in underwriting sets a precedent that could have unintended consequences for the underwriting of nongenetic risks of similar magnitude.

The prevalence of human toxocarosis in disadvantaged socioeconomic population in Europe is unknown. In Gipuzkoa the seroprevalence in middle-class children 2- to 5-years-old, and 6- to 16-year-olds, was zero (n = 135) and 4.4% (n = 320), respectively. In contrast, among socially and economically disadvantaged children the figures were 37% (n = 27) and 65.7% (n = 64). This high prevalence obliges us to consider toxocarosis as a public health problem.