Soluble α-Klotho in Liver Cirrhosis and Alcoholism.

AIMS AND BACKGROUND: Alpha Klotho is a transmembrane protein that serves as co-receptor for FGF23. Ectodomain of membrane bound α Klotho may be shed by membrane bound proteases (activated, among other factors, by tumor necrosis factor (TNF)-α) generating the soluble form of the protein (sKl) that functions as a hormone by itself. It modulates calcium influx into cells, blunts IGF-1/Insulin signaling, promotes synthesis of antioxidants, generally slows down tumor progression, delays cell senescence, is neuroprotective and promotes oligodendrocyte maturation and myelin synthesis, and muscle rejuvenation. It may be involved in inflammation and exerts antifibrogenic effects. Some of these pathways may become altered in alcoholism or liver cirrhosis, but data are scattered and scarce and an update is required. METHOD: Literature survey. RESULTS AND CONCLUSIONS: Alcohol consumption in non-alcoholics is inversely related to sKl, but alcoholic cirrhotics showed higher-than-normal sKl values in association with liver function derangement. In hepatoma cells, the intensity of Klotho staining was related to faster tumor progression and a shortened life span. Among severe alcoholic cirrhotics sKl is directly related to serum TNF-α levels, and, inversely, to brain atrophy. Given the antioxidant, anti-inflammatory, and antifibrogenic effects of Klotho, perhaps the increase in cirrhosis (and in other inflammatory conditions, such as sepsis or cancer) reflects an attempt to regulate increased inflammation, but clinical and experimental research is urgently needed in this field.

Transforming Growth Factor Beta 1 and Vascular Risk in Alcoholics.

INTRODUCTION: Transforming growth factor beta-1 (TGF-ß1) is a pleiotropic cytokine. Its relationship with atherosclerosis is debatable, protective or deleterious effects have been described. Alcoholics are at increased vascular risk. Although TGF-ß1 is increased in alcoholics, its role on vascular risk factors has not been analyzed. This is the objective of this study. PATIENTS AND METHODS: 79 heavy alcoholics and 34 controls were included. Calcium deposition in the aortic arch was assessed in the plain thorax X-ray film. Ankle-brachial index was recorded in 48 patients. All the patients underwent complete laboratory evaluation, including serum levels of TGF-ß1, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, and interferon-γ (IFN-γ).We analyzed the relationships between TGF-ß1 and vascular risk factors by both univariate (parametric or non parametric tests), or multivariate analysis to discern on which variables TGF-ß1 levels depend. RESULTS: Serum TGF-ß1 levels were higher among patients (t = 2.73; P = 0.008), but no differences exist among cirrhotics (17246 ± 11,021 pg/mL) and non-cirrhotics (21,340 ± 12,442 pg/mL). TGF-ß1 showed significant correlations with total cholesterol (r = 0.28; P = 0.017) and HDL- cholesterol (r = 0.25; P = 0.042), and inverse correlations with body mass index (BMI; ρ = -0.37; P = 0.004), IL-4 (ρ = -0.31; P = 0.009), INF-γ (ρ = -0.28; P = 0.001), and IL-6 (ρ = -0.38; P = 0.001). By multivariate analysis, only BMI, IL-6 and HDL-cholesterol showed independent relationships with TGF-ß1. No relationships were observed with ankle-brachial index or calcium in the aortic arch, hypertension, diabetes, left ventricular hypertrophy or atrial fibrillation. CONCLUSION: TGF-ß1 levels are increased in alcoholics, but are unrelated to vessel wall calcification or arterial stiffness.

Strong Coupling Corrections in Quantum Thermodynamics.

Quantum systems strongly coupled to many-body systems equilibrate to the reduced state of a global thermal state, deviating from the local thermal state of the system as it occurs in the weak-coupling limit. Taking this insight as a starting point, we study the thermodynamics of systems strongly coupled to thermal baths. First, we provide strong-coupling corrections to the second law applicable to general systems in three of its different readings: As a statement of maximal extractable work, on heat dissipation, and bound to the Carnot efficiency. These corrections become relevant for small quantum systems and vanish in first order in the interaction strength. We then move to the question of power of heat engines, obtaining a bound on the power enhancement due to strong coupling. Our results are exemplified on the paradigmatic non-Markovian quantum Brownian motion.

Clinicopathological differences between familial colorectal cancer type X and sporadic cancer in an isolated area of spain.

AIM: Very few studies have compared the epidemiological characteristics of patients with familial colorectal cancer Type X (FCCTX) with those of sporadic colorectal cancer (S-CRC). The aim of this study was to compare clinicopathological characteristics and survival between FCCTX and S-CRC in patients from a historically isolated geographical region. METHOD: A retrospective study was carried out of patients with S-CRC and FCCTX treated in the Canary Islands. Family and personal history of colorectal cancer (CRC) were recorded, together with genetic (microsatellite instability), immunohistochemical and clinical variables. RESULTS: Forty-eight (10.6%) of 451 patients were classified as FCCTX and the remaining 403 (89.4%) as S-CRC. Age at the diagnosis of tumour was significantly lower in FCCTX than in S-CRC (64.06 ± 12.65 years vs 69.13 ± 10.80 years; P = 0.01; Z = -2.48). Patients with FCCTX had a larger number of synchronous tumours (P = 0.09). Recurrence was significantly higher in FCCTX than in S-CRC (18.7% vs 8.6%; P = 0.01). Survival correlated significantly with the number of first-degree and second-degree relatives with CRC (P = 0.04; OR: 1.368, 95% CI: 1.01-1.84, and P = 0.04; OR: 1.363, 95% CI: 1.08-1.65) and with the total number of cases of CRC in the immediate family (P < 0.01; OR: 1.377, 95% CI: 1.17-1.61). Recurrence-free time was significantly lower in patients with FCCTX (log-rank = 0.01). CONCLUSION: Significant differences were found in several demographic and clinicopathological variables between patients with FCCTX and patients with S-CRC. These included increased tumour presentation under the age of 50 years and a higher recurrence rate in patients with FCCTX, suggesting an increased risk of CRC in this group.

Household transmission of SARS-CoV-2 in a rural area in South Africa.

BACKGROUND: Patterns of SARS-CoV-2 spread have varied by geolocation, with differences in seroprevalence between urban and rural areas, and between waves. Household spread of SARS-CoV-2 is a known source of new COVID-19 infections, with rural areas in sub-Saharan Africa being more prone than urban areas to COVID-19 transmission because of limited access to water in some areas, delayed health- seeking behaviour and poor access to care. OBJECTIVES: To explore SARS-CoV-2 infection incidence and transmission in rural households in South Africa (SA). METHODS: We conducted a prospective household cluster investigation between 13 April and 21 July 2021 in the Matjhabeng subdistrict, a rural area in Free State Province, SA. Adults with SARS-CoV-2 confirmed by polymerase chain reaction (PCR) tests (index cases, ICs) and their household contacts (HCs) were enrolled. Household visits conducted at enrolment and on days 7, 14 and 28 included interviewer- administered questionnaires and respiratory and blood sample collection for SARS-CoV-2 PCR and SARS-CoV-2 immunoglobulin G serological testing, respectively. Co-primary cases were HCs with a positive SARS-CoV-2 PCR test at enrolment. The incidence rate (IR), using the Poisson distribution, was HCs with a new positive PCR and/or serological test per 1 000 person-days. Associations between outcomes and HC characteristics were adjusted for intra-cluster correlation using robust standard errors. The secondary infection rate (SIR) was the proportion of new COVID-19 infections among susceptible HCs. RESULTS: Among 23 ICs and 83 HCs enrolled, 10 SARS-CoV-2 incident cases were identified, giving an IR of 5.8 per 1 000 person-days (95% confidence interval (CI) 3.14 - 11.95). Households with a co-primary case had higher IRs than households without a co-primary case (crude IR 14.16 v. 1.75, respectively; p=0.054). HIV infection, obesity and the presence of chronic conditions did not materially alter the crude IR. The SIR was 15.9% (95% CI 7.90 - 29.32). Households with a lower household density (fewer household members per bedroom) had a higher IR (IR 9.58; 95% CI 4.67 - 21.71) than households with a higher density (IR 3.06; 95% CI 1.00 - 12.35). CONCLUSION: We found a high SARS-CoV-2 infection rate among HCs in a rural setting, with 48% of households having a co-primary case at the time of enrolment. Households with co-primary cases were associated with a higher seroprevalence and incidence of SARS-CoV-2. Sociodemographic and health characteristics were not associated with SARS-CoV-2 transmission in this study, and we did not identify any transmission risks inherent to a rural setting.

[Analysis of the XIDE system in the management of overdemand for care]. / Análisis del sistema XIDE en la gestión de la sobredemanda asistencial.

OBJECTIVE: To assess the impact and suitability of the XIDE citation system in the management of over-demand for care at the Monforte de Lemos Health Center (Lugo, Spain). MATERIAL AND METHODS: Descriptive, cross-sectional, observational and analytical study. The study population was the patients with appointments to the elderly in the ordinary agenda as «forced¼ or «urgent forced¼. The population sample was obtained during the period from July 15 to August 15, 2022. The comparative analysis was performed with periods prior to the implementation of XIDE and the XIDE/observer concordance was estimated by calculating Cohen's kappa index. RESULTS: We observed an increase in care pressure, both in the number of consultations/day and in the proportion of forced consultations, which have increased by 30-34%. The group over 85 years of age and women are the majority in excess demand. The 83.04% of urgent consultations were cited through the XIDE system, the most frequent reason for consultation being «suspected COVID¼ (24.64%), with a concordance of 51.4% in this group and 65.5% globally. We appreciate a high overtriage in the assigned attention times, even when the reason for consultation coincides, with a poor statistical concordance with the observers. The high proportion in the overdemand of patients belonging to other places in the health center stands out, so that adequate management of human resources with adequate coverage of absences would reduce it by 48.5%, while the XIDE system (in the ideal assumption of absolute concordance) would only manage to reduce it by 43%. CONCLUSIONS: The low reliability of the XIDE is mainly due to inadequate triage, rather than the failure to reduce overdemand, so it cannot replace a triage system performed by health personnel.

Impact of WALANT Hand Surgery in a Secondary Care Hospital in Spain. Benefits to the Patient and the Health System.

Purpose: The aim of this study is to compare patient benefits and economic costs of hand surgeries using the wide-awake local anesthesia no tourniquet (WALANT) technique versus a conventional major outpatient suite and review outcomes and complications in a series of cases of patients operated on using the WALANT technique. Methods: A prospective cohort study was first conducted comparing 150 cases of ambulatory hand surgery (carpal tunnel syndrome and trigger finger) using the WALANT technique and not requiring an operating room setting with 150 cases of outpatient surgery performed in an operating room involving a preoperative evaluation and the use of sedation and tourniquet. Preoperative, intraoperative, and postoperative pain was monitored, and days requiring postoperative analgesia were recorded. The resources and costs were evaluated. and patient satisfaction was assessed using a specific survey.Subsequently, 580 patient medical records were retrospectively reviewed, including 419 carpal tunnel syndrome and 197 trigger finger interventions (616 WALANT surgeries). Results: Intraoperative pain was equivalent for both groups, and postoperative pain was significantly lower in the WALANT group, with a reduced need for analgesics. Satisfaction was greater for the local anesthesia group. The use of personnel resources and hospital materials was reduced in the WALANT group, with a total estimated cost savings of 1.019 USD per patient.There were no complications related to the WALANT technique and the lidocaine and adrenaline combination. We found a complication rate of 5.58%, and, in line with the literature, most complications were minor, managed conservatively, and not related to the anesthetic technique. Conclusions: Procedures such as carpal tunnel and trigger finger surgeries can be safely performed using wide-awake surgery. Patient satisfaction is higher than with the conventional procedure performed in the operating room. Pain control is excellent, especially during the postoperative period. Clinical relevance: Hand surgery patients benefit from the WALANT technique in terms of comfort and timeliness because there is no need for preoperative tests or evaluations. In addition, it represents significant savings in hospital resources. In our case series, complications were in line with those previously reported with other anesthetic techniques.

Host biomarkers for early identification of severe imported Plasmodium falciparum malaria.

BACKGROUND: Severe imported P. falciparum malaria is a source of morbi-mortality in non-endemic regions. WHO criteria don't accurately classify patients at risk of complications. There is a need to evaluate new tools such as biomarkers to better identify patients with severe imported malaria. METHODS: A case-control study was conducted in Barcelona, from January 2011-January 2021. Adult patients with microbiologically confirmed P. falciparum malaria were classified according to WHO criteria. Patients with imported non-malarial fevers were included as controls. In each group, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble triggering receptor expressed on myeloid cells (sTREM-1), C-reactive protein (CRP) and platelets were measured and their concentrations were compared between groups. New groups were made with a modified WHO severity classification and biomarkers' performance was evaluated using multiple imputation models. RESULTS: 131 participants were included: 52 severe malaria, 30 uncomplicated malaria and 49 non-malarial fever cases. All biomarkers except sTREM-1 showed significant differences between groups. Using the modified WHO severity classification, Ang-2 and CRP presented the best AUROC; 0.79 (95%CI 0.64-0.94) and 0.80(95%CI 0.67-0.93). A model combining CRP and Ang-2 showed the best AUROC, of 0.84(95%CI 0.68-0.99), with the highest sensitivity and specificity: 84.6%(95%CI 58.9-98.1) and 77.4% (95%CI 65.9-87.7), respectively. CONCLUSIONS: The combination of Ang-2 and CRP may be a reliable tool for the early identification of severe imported malaria. The use of a rapid prognostic test including the mentioned biomarkers could optimize imported malaria management, with the potential to decrease the rate of complications and hospitalizations in patients with imported malaria.

[Heterotopic ossification in SARS-CoV-2: Scintigraphic and radiological images]. / Osificación heterotópica en paciente con SARS-CoV-2: imágenes gammagráficas y radiológicas.

Patients with severe COVID-19 can develop painful range-of-motion restrictions of large joints due to heterotopic ossification. We present the case of a patient who developed hip pain after prolonged admission for severe COVID-19 pneumonia. Conventional radiography, computed tomography and bone scan showed extensive heterotopic ossification in the hips. It is probable that both local and systemic factors contribute to the development of heterotopic ossifications and it is necessary to rule out this entity when these patients reported joint pain. Early diagnosis is important to provide non-pharmacological interventions such as mild passive mobilization and anti-inflammatory medication and in refractory cases surgical resection of the ectopic bone is consider.

PET/CT calibration for post-treatment standard body scan acquisition with yttrium-90 resin micro-SPHERES.

INTRODUCTION: Among the objectives in treatments with yttrium-90 spheres, is to demonstrate that the tumoricidal dose is achieved and that hepatotoxic doses are avoided, as well as that there is no extrahepatic deposition. MATERIAL AND METHODS: We use different amounts of yttrium-90 resin micro-spheres and a NEMA NU2-2007 phantom to check if the scanner maintains a response that allows real dosimetric calculations. RESULTS: The Gemini tomograph responds linearly in a wide range of activities with R2 = 0.9983. CONCLUSION: The detection capacity of the PET equipment allows us to carry out standard body studies with dosimetric purposes with times of five minutes per bed. It also make possible to verify the absence of extrahepatic deposition of significant amounts of yttrium 90 spheres.

Telemedicine for international travelers through a Smartphone-based monitoring platform (Trip Doctor®).

BACKGROUND: Overall, more than 50% of international travelers develop symptoms while traveling and 55% of them seek medical assistance during the trip. We conducted a study to evaluate the usefulness of a Smartphone app called TRIP Doctor® to provide telemedicine to international travelers. METHODS: Participants over 18 years old attending our travel clinic at Hospital Clinic in Barcelona were invited to participate during 2017-2019. After downloading the app, the health status of the traveler was monitored on a daily basis, providing specific medical advice and offering remote contact with specialized physicians through an integrated chat, if needed. RESULTS: From 449 users, 59 (13%) contacted for medical assistance through the app during the trip. Main reasons for telemedicine were diarrhea (25.7%), skin conditions (19.7%) and fever (12.1%). Among patients who contacted, 90% of the travelers did not require to be referred to a local doctor. Symptomatic treatment was the main treatment prescribed (38%). In a 14.7% of the cases a follow-up was not required, a 63.2% recovered and 22.1% were loss of follow-up. After a multivariate analysis, duration of trip >14 days was found to be the only factor associated with the use of telemedicine (OR 2.2, CI 95% 1.1-4.5, p = 0.03). CONCLUSION: In conclusion, travelers using telemedicine travelled for longer periods of time and mostly contacted for mild symptoms which could be solved successfully by remote assistance with our specialized doctors.

[Southern European intensive care nurses' knowledge of evidence-based guidelines for preventing ventilator-associated pneumonia]. / Grado de conocimiento de las guías de prevención de la neumonía asociada a ventilación mecánica de las enfermeras de cuidados intensivos del sur de Europa.

OBJECTIVES: To assess Southern European intensive care unit nurses' knowledge about evidence-based guidelines for the prevention of ventilator-associated pneumonia and to compare these findings with a pan-European perspective. DESIGN: A sub-analysis from an observational study performed using a 9-questions, multiple-choice questionnaire performed during the period October 2006 - March 2007. SETTING: Six Southern European countries, selected from 22 participant European countries. PARTICIPANTS: Volunteer nurses from intensive care units. RESULTS: 3329 questionnaires were obtained, 1182 of them belonging to Southern European countries with a 75.8% response rate. Global average score was 45.1%, being it significantly better in the South of Europe (46.6%, P<.001). A linear multiple regression analysis showed that years of working experience (per class of increase) (B=0.154 ± (SD) 0.045) (95% CI (0.066-0.242))(p=0.001) and working in a smaller intensive care unit (B=-0.210 ± (SD) 0.059)((95% CI) -0.326-0.094)(P<.001) was independently associated with better test scores. CONCLUSIONS: Southern European critical care nurses' knowledge about ventilator-associated pneumonia prevention is poor, but significantly better than in the pan-European countries.

Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection.

OBJECTIVE: In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. METHODS: A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. RESULTS: A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. CONCLUSIONS: Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.

Influence of nuclear exchange on nonadiabatic electron processes in H(+)+H2 collisions.

H(+)+H(2) collisions are studied by means of a semiclassical approach that explicitly accounts for nuclear rearrangement channels in nonadiabatic electron processes. A set of classical trajectories is used to describe the nuclear motion, while the electronic degrees of freedom are treated quantum mechanically in terms of a three-state expansion of the collision wavefunction. We describe electron capture and vibrational excitation, which can also involve nuclear exchange and dissociation, in the E = 2-1000 eV impact energy range. We compare dynamical results obtained with two parametrizations of the potential energy surface of H(3)(+) ground electronic state. Total cross sections for E > 10 eV agree with previous results using a vibronic close-coupling expansion, and with experimental data for E < 10 eV. Additionally, some prototypical features of both nuclear and electron dynamics at low E are discussed.

Prospective study on the application of a WALANT circuit for surgery of tunnel carpal syndrome and trigger finger. / Estudio prospectivo sobre la aplicación de un circuito WALANT para la cirugía del síndrome del túnel carpiano y dedo en resorte.

OBJECTIVES: To evaluate benefits for the patient and the economic impact for the implementation of a wide awake local anesthesia no tourniquet (WALANT) hand surgery compared to traditional major outpatient circuit. METHODS: A prospective cohort study was planned comparing 150 cases of ambulatory hand surgery (carpal tunnel and trigger finger) using WALANT technique intervention out from the operating room; with another 150 which underwent intervention, outpatient setting, with preoperative evaluation, sedation and tourniquet, in the operation room. Preoperative, intraoperative and postoperative pain was monitored, as well as the days that required postoperative analgesia.The resources used and costs were evaluated. Satisfaction was evaluated using a specific survey. RESULTS: The pain during the surgery was equivalent for both groups and was significantly lower postoperatively for the WALANT group, with less need for the use of analgesics. Satisfaction was greater for the local anesthesia group. The use of personnel resources and hospital material was less for the WALANT group, with total saving calculated by 1,019€ per patient. CONCLUSIONS: Procedures such as carpal tunnel surgery and trigger finger surgery can be safely performed using wide awake surgery. Patient satisfaction is higher to conventional procedure in the operation room. Pain control is excellent, especially during the postoperative period. WALANT technique for hand surgery represents a benefit for the patient in comfort, timeliness and no need for preoperative tests or evaluation. In addition, it represents a significant savings in hospital resources.