Physicians' Perceptions as Predictors of the Future Use of the National Death Information System in Peru: Cross-sectional Study.

BACKGROUND: A computer application called the National Death Information System (SINADEF) was implemented in Peru so that physicians can prepare death certificates in electronic format and the information is available online. In 2018, only half of the estimated deaths in Peru were certified using SINADEF. When a death is certified in paper format, the probability being entered in the mortality database decreases. It is important to know, from the user's perspective, the factors that can influence the successful implementation of SINADEF. SINADEF can only be successfully implemented if it is known whether physicians believe that it is useful and easy to operate. OBJECTIVE: The aim of this study was to identify the perceptions of physicians and other factors as predictors of their behavioral intention to use SINADEF to certify a death. METHODS: This study had an observational, cross-sectional design. A survey was provided to physicians working in Peru, who used SINADEF to certify a death for a period of 12 months, starting in November 2019. A questionnaire was adapted based on the Technology Acceptance Model. The questions measured the dimensions of subjective norm, image, job relevance, output quality, demonstrability of results, perceived usefulness, perceived ease of use, and behavioral intention to use. Chi-square and logistic regression tests were used in the analysis, and a confidence level of 95% was chosen to support a significant association. RESULTS: In this study, 272 physicians responded to the survey; 184 (67.6%) were men and the average age was 45.3 (SD 10.1) years. The age range was 24 to 73 years. In the bivariate analysis, the intention to use SINADEF was found to be associated with (1) perceived usefulness, expressed as "using SINADEF avoids falsifying a death certificate" (P<.001), "using SINADEF reduces the risk of errors" (P<.001), and "using SINADEF allows for filling out a certificate in less time" (P<.001); and (2) perceived ease of use, expressed as "I think SINADEF is easy to use" (P<.001). In the logistic regression, perceived usefulness (odds ratio [OR] 8.5, 95% CI 2.2-32.3; P=.002), perceived ease of use (OR 10.1, 95% CI 2.4-41.8; P=.001), and training in filling out death certificates (OR 8.3, 95% CI 1.6-42.8; P=.01) were found to be predictors of the behavioral intention to use SINADEF. CONCLUSIONS: The behavioral intention to use SINADEF was related to the perception that it is an easy-to-use system, the belief that it improves the performance of physicians in carrying out the task at hand, and with training in filling out death certificates.

Co-infections, comorbidities, and alcohol or other substances abuses in chronic hepatitis C-related hospitalisations in Spain.

BACKGROUND: The Strategic Plan for Tackling Hepatitis C launched in 2015 in Spain has led to an important nationwide decrease in hepatitis C related hospitalisation rates. However, patients' infection progression during decades could increase their health status complexity and challenge patient's prognosis after hepatitis C eradication. METHODS: We carried out an observational retrospective study evaluating the prevalence of the main co-infections, comorbidities (risk factors and extrahepatic manifestations), and alcohol or other substances abuses in chronic hepatitis C related hospitalised patients in Spain. Data were obtained from the National Hospitalisation Registry discharges from January 1st of 2012 to December 31st of 2019. RESULTS: Between 2012 and 2019 there were 356,197 chronic hepatitis C-related hospitalisations. In-hospital deaths occurred in 11,558 (4.6%) non-advanced liver disease and in 10,873 (10.4%) advanced liver disease-related hospitalisations. Compared to 2012-2015, in 2016-2019 the proportion of hospitalisations related to non-advanced liver disease increased from 69.4% to 72.4%, while the advanced disease-related hospitalisations decreased from 30.6% to 27.6% (P<.001). In spite of the decrease in severe cases among hospitalisations, all comorbidities evaluated, and alcohol abuse increased in 2016-2019 compared to 2012-2015, while co-infections and other substances abuses decreased in the same period. In the latest period (2016-2019): 28,679 (18.3%) of the hospitalised patients had a HIV, 6928 (4.4%) a hepatitis B, and 972 (.6%) a tuberculosis co-infection. Most frequent comorbidities were diabetes (N=33,622; 21.5%); moderate to severe renal disease (N=28,042; 17.9%), chronic obstructive pulmonary disease and asthma (N=25,559; 16.3%), and malignant neoplasms (excluding hepatocellular carcinoma) (N=19,873; 12.7%). Alcohol or substances abuse was reported in 48,506 (31.0%) hospitalisations: 30,782 (19.7%) with alcohol; 29,388 (18.8%) with other substances; and 11,664 (7.5%) with both, alcohol and other substances, abuses. CONCLUSIONS: Despite the reduction in advanced liver disease hepatitis C-related hospitalisations due to prioritisation of treatment to the more severe cases, high and increasing prevalence of comorbidities and risks factors among hepatitis C-related hospitalisations have been found.

Reduction in hepatitis C-related hospitalizations after the implementation of the Strategic Plan for Tackling Hepatitis C in the Spanish National Health System: regional level differences.

This work evaluates the potential impact at territorial level of the Strategic Plan for Tackling Hepatitis C in the Spanish National Health System on hepatitis C virus (HCV)-associated hospitalizations. Chronic HCV-related hospitalization discharges from 2014 to 2018 were obtained from the National Registry of Hospitalisations. A descriptive analysis of the hospitalizations was performed for all chronic, advanced liver disease and non-advanced liver disease. Hospitalization rates were calculated at national and regional level. Year 2015 and period 2016-2018 hospitalization rates were compared to 2014 hospitalization rates using a Poisson model. Municipal standardized hospitalization rates ratios adjusted by age-group were calculated for 2016-2018 period (2014 hospitalization rates as reference). From 2014 to 2018, there were 22,352 chronic HCV-related hospitalizations. In-hospital fatality rate was 4.3% for non-advanced liver disease and 11.7% for advanced liver disease patients. National hospitalization rate decreased 22% (95% CI: 21%-22%), 16% (95% CI: 15%-17%) and 34% (95% CI: 33%-35%) in 2016-2018 compared to 2014 for all chronic, non-advanced and advanced liver disease, respectively. During 2016-2018 period, 11/19 Spanish regions achieved >20% decrease in the hospitalization rates (p < .001) for non-advanced liver disease and 19/19 (except Melilla, the rest with p < .001) for advanced liver disease. At municipal level, 84.8% and 90.2% municipalities had <20% of chronic HCV-related hospitalization need compared to 2014 adjusted by age-group. Based on the data analysed, a high impact on reducing chronic HCV-associated hospitalizations have been achieved after the implementation of the Strategic Plan for Tackling Hepatitis C in the Spanish National Health System. However, small differences between regions and rural/urban areas were noticed.

Osilodrostat: A Novel Steroidogenesis Inhibitor to Treat Cushing's Disease.

OBJECTIVE: To review data on efficacy and safety of osilodrostat (Isturisa), a novel oral steroidogenesis inhibitor for treatment of Cushing's disease (CD), a life-threatening endocrine disorder. DATA SOURCES: A PubMed/CINAHL search from inception to September 25, 2020, was performed using the following keywords: osilodrostat, 11-beta hydroxylase, pituitary, ACTH hypersecretion, and Cushing's disease. STUDY SELECTION AND DATA EXTRACTION: Phase 2 and 3 clinical trials and supplementary documents investigating osilodrostat were obtained from a primary literature search, the manufacturer's website, and the Food and Drug Administration website. These articles evaluated the clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions for osilodrostat. DATA SYNTHESIS: Osilodrostat was efficacious and safe in the treatment of CD in mostly middle-aged Caucasian women. A pivotal phase 3 study revealed a significant difference in 24-hour mean urinary free cortisol (primary end point) between osilodrostat and placebo (86% vs 29%; P < 0.001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Osilodrostat provides a potent and consistent effect in reducing life-threatening supraphysiological levels of cortisol in patients with CD. Hypocortisolism adverse effects can be mitigated by slowly increasing osilodrostat's dose at ≥2-week intervals. QT interval prolongation was noted; therefore, the QT interval must be monitored by the electrocardiogram. Increased levels of cortisol precursors during treatment with osilodrostat may increase the risk of hypokalemia, edema, and hypertension. CONCLUSIONS: Osilodrostat was efficacious in decreasing cortisol levels and safe in treating patients who have failed or are ineligible for pituitary surgery. Although risks exist, a pivotal clinical trial revealed efficacy in 86% of participants.

Preoperative hepatic artery embolization before distal pancreatectomy plus celiac axis resection does not improve surgical results: A Spanish multicentre study.

BACKGROUND: Distal pancreatectomy with celiac axis resection (DP-CAR) is a surgical procedure with high morbidity and mortality performed in patients with locally advanced pancreatic cancer. Preoperative embolization of hepatic artery (PHAE) has been postulated as a technical option to increase resection rate. OBJECTIVE: comparison of morbidity and mortality at 90 days, operative time, hospital stay and survival between patients that performed DP-CAR with and without PHAE. METHODS: Observational retrospective multicentre study. INCLUSION CRITERIA: patient operated in Spanish centers with DP-CAR for pancreatic cancer from April 2004 until 23 June 2018. Preoperative (PHAE, neodjuvant treatment), intraoperative (operative time and blood loss) and postoperative data (morbidity, hospital stay, R0 and survival) were studied. Complications were measured with Clavien classification at 90 days. Specific pancreatic complications were measured using ISGPS classifications. Data were analyzed using R version 3.1.3 (http://www.r-project.org). Level of significance was set at 0.05. RESULTS: 41 patients were studied. 26 patients were not embolized (NO-PHAE group) and 15 patients received PHAE. Preoperative BMI and percentage of neoadjuvant chemotherapy were the only preoperative variables different between both groups. The operative time in the PHAE group was shorter (343 min) than in the non-PHAE group (411 min) (p < 0.06). Major morbidity (Clavien > IIIa) and mortality at 90 days were higher in the PHAE group than in the non-PHAE group (60% vs 23% and 26.6% vs 11.6% respectively) (p < 0.004). No statistical difference in overall survival was observed between both groups (p = 0.14). CONCLUSION: In our study PHAE is not related with less postoperative morbidity. Even more, major morbidity (Clavien III-IV) and mortality was higher in PHAE group.

Circulating Tumor Cells in Patients Undergoing Resection of Colorectal Cancer Liver Metastases. Clinical Utility for Long-Term Outcome: A Prospective Trial.

BACKGROUND: Patients with resected colorectal cancer liver metastases display heterogeneous clinical behavior. The identification of new prognostic factors would help in making more accurate decisions. OBJECTIVE: The aim of this study was to evaluate the survival impact of circulating tumor cells (CTCs) in this setting. METHODS: We conducted a prospective study of patients with resected liver metastases of colorectal cancer. Patients were included in the study from February 2009 to January 2013. The CellSearch System™ was employed for the detection of pre- and postsurgery CTCs. A positive test was defined as two or more CTCs/7.5 mL of blood. Recurrence rate, disease-free survival, and overall survival were calculated, and univariate and multivariate analyses were performed. RESULTS: Forty-four patients were included in our study. After a median follow-up of 60 months (range 28-74), 32 patients experienced recurrence (72.7%). The CTCs number was determined and the test was positive in 8 patients (18.6%) before surgery and 13 patients (29.5%) after surgery. The postoperative detection of CTCs was not related to any clinical outcome; however, the preoperative detection of CTCs was significantly related to behavior. All patients in the preoperative CTC-positive group relapsed, versus 65% in the CTC-negative group (p = 0.051). Disease-free survival was 19 months in the preoperative CTC-negative group versus 7 months in the CTC-positive group (p = 0.01). Additionally, overall survival was 69 months in the preoperative CTC-negative group versus 17 months in the CTC-positive group (p = 0.004). Preoperative CTC count remained significant in multivariate analysis. CONCLUSIONS: In this cohort of colorectal cancer liver metastases patients, the presence of two or more preoperative CTCs was associated with disease progression and poor survival despite complete resection.

Reducing Length of Stay Using a Robotic-assisted Approach for Retromuscular Ventral Hernia Repair: A Comparative Analysis From the Americas Hernia Society Quality Collaborative.

OBJECTIVE: The aim of this study was to compare length of stay (LOS) after robotic-assisted and open retromuscular ventral hernia repair (RVHR). BACKGROUND: RVHR has traditionally been performed by open techniques. Robotic-assisted surgery enables surgeons to perform minimally invasive RVHR, but with unknown benefit. Using real-world evidence, this study compared LOS after open (o-RVHR) and robotic-assisted (r-RVHR) approach. METHODS: Multi-institutional data from patients undergoing elective RVHR in the Americas Hernia Society Quality Collaborative between 2013 and 2016 were analyzed. Propensity score matching was used to compare median LOS between o-RVHR and r-RVHR groups. This work was supported by an unrestricted grant from Intuitive Surgical, and all clinical authors have declared direct or indirect relationships with Intuitive Surgical. RESULTS: In all, 333 patients met inclusion criteria for a 2:1 match performed on 111 r-RVHR patients using propensity scores, with 222 o-RVHR patients having similar characteristics as the robotic-assisted group. Median LOS [interquartile range (IQR)] was significantly decreased for r-RVHR patients [2 days (IQR 2)] compared with o-RVHR patients [3 days (IQR 3), P < 0.001]. No differences in 30-day readmissions or surgical site infections were observed. Higher surgical site occurrences were noted with r-RVHR, consisting mostly of seromas not requiring intervention. CONCLUSIONS: Using real-world evidence, a robotic-assisted approach to RVHR offers the clinical benefit of reduced postoperative LOS. Ongoing monitoring of this technique should be employed through continuous quality improvement to determine the long-term effect on hernia recurrence, complications, patient satisfaction, and overall cost.

Saving lives through certifying deaths: assessing the impact of two interventions to improve cause of death data in Perú.

BACKGROUND: Mortality statistics derived from cause of death data are an important source of information for population health monitoring, priority setting and planning. In Perú, almost all death certificates are issued by doctors because it is a legal requirement. However, the quality of cause of death data is poor. In August 2016, the Ministry of Health of Perú decided to make two specific interventions to improve cause of death data: to introduce an online death certification system and to train doctors in standard death certification practices. METHODS: The study comprised a random sample of 300 pre-intervention death certificates, 900 death certificates that were part of the online intervention, and 900 death certificates that were part of both the online and training interventions. All the deaths had occurred between January and September 2017. We used the Assessing the quality of death certification tool from the University of Melbourne for the assessment. We examined the frequency of common errors in death certificates, the frequency of any error and the average error score for each category of: age group, sex, doctor's seniority, doctor's speciality, level of health facility and broad cause of death. RESULTS: The average error score declined by 38% due to the online intervention and by a further 26% due to the training intervention. Improved certification practices remained after controlling for potentially confounding factors. Main improvements were reductions in the absence of a time interval (66% of certificates), incorrect sequence of causes (22%), and ill-defined conditions (13%). CONCLUSIONS: This study demonstrates how the two interventions introduced by the Ministry of Health in Perú improved the correctness of death certificates. The study also provides evidence on necessary changes to the training program to address the poor certification practices that have remained after implementation of the online system.

[New Approaches for Young Surgeons - Students' Symposium on Minimally Invasive Surgery]. / Neue Wege zum chirurgischen Nachwuchs ­ Studierendenforum für Minimal Invasive Chirurgie.

Background Physician shortage is particularly striking in surgical specialities. Umbrella organisations are making an effort to recruit medical students. Students' symposia during congresses seem to provide a promising approach to developing motivation and promoting interest. An exemplary students' symposium took place at the three nations meeting for minimally invasive surgery (MIS). Our aim was to evaluate the students' symposium from the students' perspective, in order to give recommendations for the future. Methods Of a total of 60 participants, half (30/60) completed the survey. Using a 5-point Likert scale, students evaluated items on the agenda, increase in interests, personal benefit and likelihood of future participation. Results Sixty percent (18/30) of the participants in the student forum reported enhanced interest in MIC - the largest increase found. For surgery in general and for robotic surgery in particular, an increase was reported by 57% (17/30) of the students. Of all the items on the agenda, laparoscopic hands-on experience was rated best - with a positive rating from 90% (27/30) of the students. Students expressed the wish for improved personal exchange with experts and professionals. Two thirds (40/60) of the students stated that future participation was definite or very likely. Discussion The increase in interest in MIS and surgery in general demonstrated the success of the students' symposium. Hands-on experiences was very popular. Future events should focus on personal exchange between students and experts. This seems necessary to reduce prejudice in the debate on a well-adjusted work-life balance. With a view to physician shortage in surgical specialties, students' symposia are a valuable option that should be firmly established and consistently developed.

[Satisfaction and perceived quality of people insured by the Social Health Protection in Mexico. Methodological foundations]. / Satisfacción y calidad percibida de afiliados al Sistema de Protección Social en Salud de México. Fundamentos metodológicos.

OBJECTIVE:: To describe the conceptual framework and methods for implementation and analysis of the satisfaction survey of the Mexican System for Social Protection in Health. MATERIALS AND METHODS:: We analyze the methodological elements of the 2013, 2014 and 2015 surveys, including the instrument, sampling method and study design, conceptual framework, and characteristics and indicators of the analysis. RESULTS:: The survey captures information on perceived quality and satisfaction. Sampling has national and State representation. Simple and composite indicators (index of satisfaction and rate of reported quality problems) are built and described. The analysis is completed using Pareto diagrams, correlation between indicators and association with satisfaction by means of multivariate models. CONCLUSIONS:: The measurement of satisfaction and perceived quality is a complex but necessary process to comply with regulations and to identify strategies for improvement. The described survey presents a design and rigorous analysis focused on its utility for improving.

Acute recurrent pancreatitis secondary to hepatocellular carcinoma invading the biliary tree.

Hepatocellular carcinoma rarely invades the biliary tree. Clots or tumor embolus passing though the bile duct can cause pancreatitis by a mechanism similar to gallstone pancreatitis. We present the case of a patient with recurrent acute pancreatitis, initially suspicious of biliary origin. Despite cholecystectomy he had new episodes of acute pancreatitis. Hepatocellular carcinoma was diagnosed after the third episode. ERCP findings suggested the presence of a fistula connecting the tumor and the biliary tree. The patient was operated and the hepatocellular carcinoma was resected. Its pathological analysis confirmed the communication between the tumor and the biliary duct.

Effectiveness and risk factors for virological outcome of darunavir-based therapy for treatment-experienced HIV-infected patients.

OBJECTIVE: We evaluated the effectiveness of darunavir (DRV) treatment plus an optimized background regimen in 120 HIV-1 treatment-experienced patients. DESIGN: Retrospective cohort, multicenter study. METHODS: Adults >16 years with virological treatment failure starting therapy with a DRV-containing regimen were included. Effectiveness was evaluated as the percentage of patients with an undetectable HIV-1 RNA viral load (<50 and <200 copies/mL) after 48 weeks, and changes in CD4+ cell counts. We evaluated the risk factors associated with treatment failure. RESULTS: Of the cohort, 83 % were men with a median age of 45 years (interquartile range, IQR 40-51). They had experienced treatment for a median of 13 years (IQR 9-17) with a median of six previous regimens (IQR 4-7), all using protease inhibitors. After treatment, 82 % (95 % confidence interval, CI 74-88 %) of patients had an HIV-1 RNA viral load <200 copies/mL and 69 % (95 % CI 60-76 %) had <50 copies/mL. The CD4+ cell count increased by 378 cells/µL (IQR 252-559; P < 0.001 vs. baseline). Risk factors associated with poor outcome were age >40 years [odds ratio, OR 0.15 (95 % CI 0.10-0.78); P = 0.015], use of raltegravir in the regimen [OR 0.37 (95 % CI 0.10-0.97); P = 0.046], and baseline CD4+ cell count <200 cells/µL [OR 2.79 (95 % CI 1.11-6.97); P = 0.028]. CONCLUSION: In this Mexican cohort Darunavir was metabolically safe, well tolerated and achieved high rates of virological suppression in highly treatment-experienced patients infected with HIV-1.

Trends in Sports- and Recreation-Related Traumatic Brain Injuries Treated in US Emergency Departments: The National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP) 2001-2012.

IMPORTANCE: Sports- and recreation-related traumatic brain injuries (SRR-TBIs) are a growing public health problem affecting persons of all ages in the United States. OBJECTIVE: To describe the trends of SRR-TBIs treated in US emergency departments (EDs) from 2001 to 2012 and to identify which sports and recreational activities and demographic groups are at higher risk for these injuries. DESIGN: Data on initial ED visits for an SRR-TBI from the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP) for 2001-2012 were analyzed. SETTING: NEISS-AIP data are drawn from a nationally representative sample of hospital-based EDs. PARTICIPANTS: Cases of TBI were identified from approximately 500,000 annual initial visits for all causes and types of injuries treated in EDs captured by NEISS-AIP. MAIN OUTCOME MEASURE(S): Numbers and rates by age group, sex, and year were estimated. Aggregated numbers and percentages by discharge disposition were produced. RESULTS: Approximately 3.42 million ED visits for an SRR-TBI occurred during 2001-2012. During this period, the rates of SRR-TBIs treated in US EDs significantly increased in both males and females regardless of age (all Ps < .001). For males, significant increases ranged from a low of 45.8% (ages 5-9) to a high of 139.8% (ages 10-14), and for females, from 25.1% (ages 0-4) to 211.5% (ages 15-19) (all Ps < .001). Every year males had about twice the rates of SRR-TBIs than females. Approximately 70% of all SRR-TBIs were reported among persons aged 0 to 19 years. The largest number of SRR-TBIs among males occurred during bicycling, football, and basketball. Among females, the largest number of SRR-TBIs occurred during bicycling, playground activities, and horseback riding. Approximately 89% of males and 91% of females with an SRR-TBI were treated and released from EDs. CONCLUSION AND RELEVANCE: The rates of ED-treated SRR-TBIs increased during 2001-2012, affecting mainly persons aged 0 to 19 years and males in all age groups. Increases began to appear in 2004 for females and 2006 for males. Activities associated with the largest number of TBIs varied by sex and age. Reasons for the reported increases in ED visits are unknown but may be associated with increased awareness of TBI through increased media exposure and from campaigns, such as the Centers for Disease Control and Prevention's Heads Up. Prevention efforts should be targeted by sports and recreational activity, age, and sex.

On-the-field performance of quintuple-play long-reach OFDM-based WDM-PON optical access networks.

In this paper the on-the-field performance of a WDM-PON optical access providing quintuple-play services using orthogonal frequency division multiplexing (OFDM) modulation is evaluated in a real fiber-to-the-home (FTTH) network deployed by Towercom operator in Bratislava (Slovakia). A bundle of quintuple-play services comprising full-standard OFDM-based signals (LTE, WiMAX, UWB and DVB-T) and an ad-hoc OFDM-GbE signal is transmitted in coexistence per single user. Both downstream and upstream transmission performances are evaluated in different on-the-field long-reach optical link distance configurations. Four wavelength multi-user transmission of quintuple-play OFDM services is demonstrated exceeding 60.8 km reach in standard single mode fiber.

Treatment with metadoxine and its impact on early mortality in patients with severe alcoholic hepatitis.

BACKGROUND & AIM: Despite treatment with glucocorticoids, mortality remains high in patients with severe alcoholic hepatitis. Oxidative stress and depletion of mitochondrial glutathione are implicated factors in liver injury. The aim of this study was to evaluate the impact of the addition of metadoxine, a drug which possesses a multifactorial mechanism of action, including antioxidant properties, to standard treatment with glucocorticoids in patients with severe alcoholic hepatitis. MATERIAL AND METHODS: This randomized open label clinical trial was performed in Mexico's General Hospital (Registry Key DIC/10/107/03/043). We randomized 70 patients with severe alcoholic hepatitis. The first group received prednisone (40 mg/day), and the second group received prednisone (40 mg/day) plus metadoxine tablets (500 mg three times daily). The duration of treatment in both groups was 30 days. Survival at 30 and 90 days, development of complications, adverse events and response to treatment (Lille model) were assessed. RESULTS: In the group receiving metadoxine, significant improvements were observed, as follows: survival at 30 days (74.3 vs. 45.7%, P = 0.02); survival at 90 days (68.6 vs. 20.0%, P = 0.0001). There was less development or progression of encephalopathy (28.6 vs. 60.0%, P = 0.008) and hepatorenal syndrome (31.4 vs. 54.3%, P = 0.05), and the response to treatment (Lille model) was higher in the metadoxine group (0.38 vs. 0.63, P = 0.001; 95% CI 0.11 to 0.40). There were no differences between groups regarding the development or progression of variceal hemorrhage or infection. The incidence of adverse events, mainly gastrointestinal, was similar in both groups. CONCLUSIONS: Addition of metadoxine to glucocorticoid treatment improves the short-term survival of patients with severe alcoholic hepatitis and diminishes the development or progression of encephalopathy and hepatorenal syndrome.

[Severe hypereosinophilia as a paraneoplastic syndrome in a patient with differentiated thyroid cancer] / Hipereosinofilia severa como síndrome paraneoplásico en un paciente con cáncer diferenciado de tiroides.

In solid tumors, hypereosinophilia is a rare phenomenon and is mainly associated with mucin-secreting carcinomas. Thyroid tumors associated with neutrophilia and/or eosinophilia have been described exclusively in patients with anaplastic thyroid cancer. Eosinophilia associated with papillary thyroid cancer is extremely rare and there are very few cases currently described. It has been suggested that three cytokines, namely interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage colony-stimulating factor (GM-CSF), may act as a peptide potential eosinophilic. To date, only three patients with differentiated thyroid cancer associated with eosinophilia have been reported, two of the papillary type and one of the medullary type. A 48-year-old patient consulted in 2022 due to bilateral cervical lymphadenopathy of 3 years' duration associated with wasting syndrome and hypereosinophilia. PET CT was requested, which showed hypermetabolic focus in the right thyroid lobe and lymph node, lung, bone, and liver metastases; Thyroid ultrasound showing a nodule of high suspicion of malignancy and a conglomerate of lymphadenopathy in the right lobe with positive needle wash for thyroglobulin. Hypereosinophilia was evaluated with initial leukocytosis values of GB 30,310/mm3 (10,608/mm3 of eosinophils) to maximum values of GB 77,090/mm3 (eosinophils 20,814/mm3). It was interpreted as paraneoplastic syndrome and corticosteroid therapy was started at immunosuppressive doses without response. Our observations presented in this article are in line with most studies reflecting that paraneoplastic hypereosinophilia is characterized by more advanced disease and poor prognosis.

En los tumores sólidos la hipereosinofilia es un fenómeno raro y se asocia principalmente con carcinomas secretores de mucina. Los tumores tiroideos asociados a neutrofilia y/o eosinofilia se han descrito exclusivamente en pacientes con cáncer anaplásico de tiroides. La eosinofilia asociada con cáncer papilar de tiroides es extremadamente rara y se encuentran muy pocos casos descriptos actualmente. Se ha sugerido que tres citocinas, a saber, la interleucina-3 (IL-3), la interleucina-5 (IL-5) y el factor estimulante de colonias de granulocitos y macrófagos (GM-CSF), pueden actuar como un péptido eosinofílico potencial. Hasta el momento solo se han reportado tres pacientes con cáncer diferenciado de tiroides asociados a eosinofilia, dos de tipo papilar y uno de tipo medular. Paciente de 48 años consultó en el año 2022 por adenopatías cervicales bilaterales de 3 años de evolución asociado a síndrome consuntivo e hipereosinofilia. Se solicitó PET CT que evidenció foco hipermetabólico en lóbulo tiroideo derecho y metástasis ganglionares, pulmonares, óseas y hepáticas; ecografía tiroidea que evidencia en lóbulo derecho nódulo de alta sospecha de malignidad y conglomerado de adenopatías con lavado de aguja positivo para tiroglobulina. Evaluada la hipereosinofilia con valores iniciales de leucocitosis de GB 30310/mm3 (10608/mm3 de eosinófilos) hasta valores máximos de GB 77090/mm3 (eosinófilos 20814/mm3) se interpretó como síndrome paraneoplásico y se inició corticoterapia en dosis inmunosupresoras sin respuesta. Nuestras observaciones presentadas en este artículo están en línea con la mayoría de los estudios que reflejan que la hipereosinofilia paraneoplásica se caracteriza por una enfermedad más avanzada y un mal pronóstico.

Bioaccessibility of chlorogenic acid and curcumin co-encapsulated in double emulsions with the inner interface stabilized by functionalized silica nanoparticles.

The aim of this study was to evaluate the bioaccessibility of chlorogenic acid (CA) and curcumin co-encapsulated in Pickering double emulsions (DEs) with the inner interface stabilized by hydrophobically modified silica nanoparticles with myristic acid (SNPs-C14) or tocopherol succinate (SNPs-TS). Both SNPs-C14 and SNPs-TS showed contact angles > 90°. Pickering W1/O emulsions were formulated with 4 % of both types of SNPs. Pickering DEs showed higher creaming stability (5-7 %, day 42) and higher CA encapsulation efficiency (EE; 80 %) than control DE. The EE of curcumin was > 98 % in all the DEs. CA was steadily released from Pickering DEs during digestion, achieving bioaccessibility values of 58-60 %. Curcumin was released during the intestinal phase (∼80 % bioaccessibility in all DEs). Co-loaded DEs showed similar bioaccessibility for CA and curcumin than single-loaded. SNPs-C14 and SNPs-TS were suitable to stabilize the W1:O interface of DEs as co-delivery systems of bioactive compounds with health-promoting properties.

The effect of the COVID-19 pandemic on the incidence and resistance in Gram-negative bacilli and antimicrobial consumption in the Intensive Care Units of a referral hospital in Buenos Aires.

An increase in the antimicrobial consumption in hospitals during the COVID-19 pandemic, accompanied by an increase of infections due to multidrug-resistant (MDR) bacteria has been reported. METHODOLOGY: A retrospective time series study from Intensive Care Units, to address changes in antibiotic consumption (DDD/1000 patients/day), the incidence of Gram-negative bacilli (GNB) and the mechanism of resistance. Antibiotics were categorised in group 1 (agents against multi-drug resistant MDR GNB) and group 2 (agents against non-MDR infections). Bacteriological samples included respiratory samples and blood cultures. Periods were divided into pre-pandemic (July 2019 to March 2020) and pandemic (April 2020 to March 2022). Correlation coefficients (r) were analyzed and Mann-Whitney test was performed to compare both periods. RESULTS: During the study period, GNB incidence, group 1 antibiotics consumption and resistance mechanisms increased, whereas group 2 antibiotics decreased. A significant positive correlation was observed between the consumption of antibiotics in group 1 and the incidence of GNB (r=0,63; p<0.001) and resistance (r=0,52; p=0.002). Significant differences were found between pre-pandemic and pandemic periods regarding the medians of group 1 consumption (520 [408-570] vs 753 [495-851] DDD/1000 patients/day; p=0.029); incidence of GNB (12 [10-13] vs 43 [25-52.5] cases/month; p<0.001) and resistance mechanisms (5 [4-8] vs 17 [10-25] cases/month; p<0.001), ESBL (2 [1-2] vs 6 [3-8] cases/month; p<0.001) and MBL (0 [0-0] vs 6 [1.75-8.5] cases/month; p <0.001). CONCLUSIONS: During the pandemic, the rise of GNB incidence and in the amount of resistance mechanisms significantly correlated with the increase in consumption of agents against MDR strains.

Antigen specificity shapes antibody functions in tuberculosis.

Tuberculosis (TB) is the number one infectious disease cause of death worldwide in part due to an incomplete understanding of immunity. Emerging data highlight antibody functions as correlates of protection and disease across human TB. However, little is known about how antibody functions impact Mycobacterium tuberculosis (Mtb), the causative agent. Here, we use antigen specificity to understand how antibodies mediate host-Mtb interactions. We focus on Mtb cell wall and ESAT-6 & CFP-10, critical bacterial structural and secreted virulence proteins. In polyclonal IgG from TB patients, we observe that antigen specificity alters IgG subclass and glycosylation that drives Fc receptor binding and effector functions. Through in vitro models of Mtb macrophage infection we find that Mtb cell wall IgG3, sialic acid, and fucose increase opsonophagocytosis of extracellular Mtb and bacterial burden, suggesting that some polyclonal IgG enhance disease. In contrast, ESAT-6 & CFP-10 IgG1 inhibits intracellular Mtb, suggesting that antibodies targeting secreted virulence factors are protective. We test this hypothesis by generating a mAb that reacts to ESAT-6 & CFP-10 and show that it alone inhibits intracellular Mtb. Understanding which antigens elicit antibody mediated disease enhancement and or protection will be critical in appreciating the many roles for antibodies in TB.

Interaction between type 2 diabetes and past COVID-19 on active tuberculosis.

BACKGROUND: The global setback in tuberculosis (TB) prevalence and mortality in the post-COVID-19 era have been partially attributed to pandemic-related disruptions in healthcare systems. The additional biological contribution of COVID-19 to TB is less clear. The goal of this study was to determine if there is an association between COVID-19 in the past 18 months and a new TB episode, and the role played by type 2 diabetes mellitus (DM) comorbidity in this relationship. METHODS: A cross-sectional study was conducted among 112 new active TB patients and 373 non-TB controls, identified between June 2020 and November 2021 in communities along the Mexican border with Texas. Past COVID-19 was based on self-report or positive serology. Bivariable/multivariable analysis were used to evaluate the odds of new TB in hosts with past COVID-19 and/or DM status. RESULTS: The odds of new TB were higher among past COVID-19 cases vs. controls, but only significant among DM patients (aOR 2.3). The odds of TB given DM was 2.7-fold among participants without past COVID-19 and increased to 7.9-fold among those with past COVID-19. CONCLUSION: DM interacts with past COVID-19 synergistically to magnify the risk of TB. Latent TB screening and prophylactic treatment, if positive, is recommended in this COVID-19/DM/latent TB high-risk group.