Physiologically Based Trimester-Specific Serum Ferritin Thresholds for Iron Deficiency in US Pregnant Women.

Serum ferritin (SF) concentration is the most widely used indicator for iron deficiency (ID). During pregnancy, the World Health Organization recently recommended SF thresholds for ID of <15 µg/L for the 1st trimester of pregnancy, based on expert opinion, and made no recommendations for the 2nd and 3rd trimesters. We examined the relationship of SF with two independent indicators of the onset of iron-deficient erythropoiesis, hemoglobin (Hb) and soluble transferrin receptor 1 (sTfR1), in cross-sectional data from NHANES for 1999-2010 and 2015-2018. We included 1288 pregnant women 15-49 years and excluded women with inflammation or potential liver disease. We used restricted cubic spline (RCS) regression analysis to determine SF thresholds for iron-deficient erythropoiesis. SF decreased during pregnancy; geometric mean SF was higher during the 1st and lower during the 2nd and 3rd trimesters. Using RCS analysis, the SF thresholds identified during pregnancy were <25.8 (18.1, 28.5) µg/L during 1st trimester, <18.3 (16.3, 22.9) µg/L during 2nd trimester, and <19.0 (14.4, 26.1) µg/L during 3rd trimester. These SF threshold levels track concentrations of hepcidin, the iron regulatory hormone controlling the mobilization of iron stores. A SF concentration of <15 µg/L as the criterion for ID may underestimate the true prevalence of ID throughout pregnancy. In our study, an additional one of every ten pregnant women would be recognized as iron deficient by using the physiologically based thresholds at SF of about 25 µg/L during the 1st and of about 20 µg/L during the 2nd and 3rd trimesters.

Preoperative Levosimendan in Patients With Severe Left Ventricular Dysfunction Undergoing Isolated Coronary Artery Bypass Grafting: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To verify the impact of preoperative levosimendan on patients with severe left ventricular dysfunction (ejection fraction <35%) undergoing isolated coronary artery bypass grafting. DESIGN: A meta-analysis. SETTING: Hospitals. PARTICIPANTS: The authors included 1,225 patients from 6 randomized controlled trials. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors performed a meta-analysis of trials that compared preoperative levosimendan with placebo or no therapy, reporting efficacy and safety endpoints. Statistical analyses used mean differences and risk ratios (RR), with a random effects model. Six studies were included, comprising 1,225 patients, of whom 615 (50.2%) received preoperative levosimendan, and 610 (49.8%) received placebo/no therapy. Preoperative levosimendan showed a lower risk of all-cause mortality (RR 0.31; 95% CI 0.16-0.60; p < 0.01; I2 = 0%), postoperative acute kidney injury (RR 0.44; 95% CI 0.25-0.77; p < 0.01; I2 = 0%), low-cardiac-output syndrome (RR 0.45; 95% CI 0.30-0.66; p < 0.001; I2 = 0%), and postoperative atrial fibrillation (RR 0.49; 95% CI 0.25-0.98; p = 0.04; I2 = 85%) compared to control. Moreover, levosimendan significantly reduced the need for postoperative inotropes and increased the cardiac index at 24 hours postoperatively. There were no differences between groups for perioperative myocardial infarction, hypotension, or any adverse events. CONCLUSION: Preoperative levosimendan in patients with severe left ventricular dysfunction undergoing isolated coronary artery bypass grafting was associated with reduced all-cause mortality, low-cardiac-output syndrome, acute kidney injury, postoperative atrial fibrillation, and the need for circulatory support without compromising safety.

Outcome of patients supported with the HeartMate 3 after extracorporeal life support: On behalf of the Durable Mechanical Circulatory Support After Extracorporeal Life Support Study Group.

OBJECTIVES: The Durable Mechanical Circulatory Support System After Extracorporeal Life Support registry is a multicenter registry of patients who were bridged from extracorporeal life support to a durable mechanical circulatory support system. Although numerous studies have highlighted the favorable outcomes after implantation of the HeartMate 3 (Abbott), the objective of our study is to examine the outcomes of patients who received HeartMate 3 support after extracorporeal life support. METHODS: Data of patients undergoing HeartMate 3 implantation from January 2016 to April 2022 at 14 centers were collected and evaluated. Inclusion criteria were patients with extracorporeal life support before HeartMate 3 implantation. The outcome was reported and compared with patients receiving other types of pumps. RESULTS: A total of 337 patients were bridged to durable mechanical circulatory support system after extracorporeal life support in the study period. Of those patients, 140 were supported with the HeartMate 3. The other types of pumps included 170 HeartWare HVADs (Medtronic) (86%), 14 HeartMate II devices (7%), and 13 (7%) other pumps (7%). Major postoperative complications included right heart failure requiring temporary right ventricular assist device in 60 patients (47%). Significantly lower postoperative stroke (16% vs 28%, P = .01) and pump thrombosis (3% vs 8%, P = .02) rates were observed in the patients receiving the HeartMate 3. The 30-day, 1-year, and 3-year survivals in patients receiving the HeartMate 3 were 87%, 73%, and 65%, respectively. CONCLUSIONS: In this critically ill patient population, the survivals of patients who were transitioned to the HeartMate 3 are deemed acceptable and superior to those observed when extracorporeal life support was bridged to other types of durable mechanical circulatory support systems.

Trends in Micronutrient Interventions, Anemia, and Iron Deficiency among Women and Children in Guatemala, 2009-2019.

Background: Food fortification and micronutrient supplementation are public health strategies to improve micronutrient status in Guatemala; their population effectiveness has not been evaluated in recent years. Objective: We evaluated trends in food fortification, micronutrient supplementation, anemia, and iron deficiency among nonpregnant women aged 15-49 y [women of reproductive age (WRA)] and children 6-59 aged mo [preschool age children (PSC)]. Method: Nationally representative serial cross-sectional surveys were used to assess changes in hemoglobin, anemia, ferritin, iron deficiency, iron deficiency anemia, and self-reported consumption of fortifiable foods and micronutrient supplements during 2008/2009, 2013, 2015, 2016, 2017/2018, and 2018/2019. Predictors of hemoglobin and ferritin were assessed using generalized linear mixed models adjusted for survey year as random effects, and the consumption of fortifiable foods, supplements, and other potential confounders were fixed effects. Results: Multiple micronutrient powder consumption among PSC during the previous 3 mo was 53.3% (95% CI: 49.4, 57.2) in 2013 and 33.6% (28.8, 38.4) in 2018/2019. Anemia among PSC was 11.3% (8.0, 14.5) in 2008/2009 and 6.1% (3.6, 8.6) in 2018/2019. Anemia among WRA was 10.7% (7.2, 14.2) in 2008/2009 and 3.9% (2.7, 5.2) in 2018/2019. Iron deficiency among PSC was 15.5% (12.1, 19.0) in 2008/2009 and 10.9% (7.4, 14.5) in 2016 (lowest), but 17.1 (13.3, 21.0) in 2017/2018 (highest). Iron deficiency among WRA was 14.9% (11.6, 18.2) in 2008/2009, 13.8% (11.8, 15.8) in 2013 (lowest), and 18.9% (16.3, 21.6) in 2017/2018 (highest). Wheat flour/bread consumption was positively associated with hemoglobin among PSC, and sugar consumption was positively associated with hemoglobin among WRA. The reported consumption of fortifiable foods was not associated with ferritin among PSC or WRA. Conclusions: Guatemala has implemented multiple food fortification strategies, and anemia has declined. Increases in iron deficiency in 2017-2019 warrant further attention. Secular trends toward poverty alleviation, education, and development might be responsible for changes not explained by the micronutrient interventions evaluated.

Insuficiencia respiratoria en una paciente con síndrome de Sézary / Respiratory failure in a patient with Sézary syndrome

Paciente de 44 años de sexo femenino, sin ninguna enfermedad de base preexistente, con una historia de aproximadamente diez meses de presentar lesiones eritemato-descamativas pruriginosas inicialmente localizadas en extremidades inferiores y que luego se generalizaron en todo el cuerpo, asociándose a la pérdida de peso de aproximadamente 15 kg. El manejo inicial consistió en corticoides tópicos y antihistamínicos orales con poca respuesta clínica. Se inició el estudio por dermatología y se confirmó el diagnóstico inicial de neoplasia cutánea maligna de células T. Luego se realizó el frotis de médula ósea, en el que se identificaron células «cerebriformes¼ que confirmaron el diagnóstico de síndrome de Sézary. La paciente recibió esquema de quimioterapia ciclofosfamida, doxorrubicina, vincristina, etopósido y prednisona. La respuesta inicial fue favorable, con alta hospitalaria y seguimiento en la consulta externa. Transcurridos tres meses de tratamiento, la paciente consultó por episodio febril, tos productiva más distrés respiratorio asociado a estertores basales bilaterales, presentó insuficiencia respiratoria y durante la inducción a la ventilación mecánica sufrió un paro cardiorrespiratorio y falleció

44-year-old female patient, with no preexisting underlying disease, with a history of approximately ten months of presenting pruritic erythematous-desquamative lesions initially localized in the lower extremities and later generalized throughout the body, associated with weight loss of 15 kg. Treatment. Initial management consisted of topical corticosteroids and oral antihistamines with little clinical response. A dermatology wok-up was initiated, and the initial diagnosis of malignant T-cell neoplasm was confirmed. A bone marrow smear was performed, in which "cerebriform" cells were identified, confirming the diagnosis of Sézary syndrome. The patient received cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone chemotherapy. Outcome. The initial response was favorable, with hospital discharge and outpatient follow-up. After three months of treatment, the patient consulted for a febrile episode, productive cough plus respiratory distress associated with bilateral basal rales, presented respiratory failure, and during induction of mechanical ventilation suffered cardiorespiratory arrest and died.

Comparison of Current World Health Organization Guidelines with Physiologically Based Serum Ferritin Thresholds for Iron Deficiency in Healthy Young Children and Nonpregnant Women Using Data from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Current WHO serum ferritin (SF) thresholds for iron deficiency (ID) in children (<12 µg/L) and women (<15 µg/L) are derived from expert opinion based on radiometric assays in use decades ago. Using a contemporary immunoturbidimetry assay, higher thresholds (children, <20 µg/L; women, <25 µg/L) were identified from physiologically based analyses. OBJECTIVE: We examined relationships of SF measured using an immunoradiometric assay from the era of expert opinion with 2 independently measured indicators of ID, hemoglobin (Hb) and erythrocyte zinc protoporphyrin (eZnPP), using data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). The SF at which circulating Hb begins to decrease and eZnPP begins to increase provides a physiological basis for identifying the onset of iron-deficient erythropoiesis. METHODS: We analyzed NHANES III cross-sectional data from 2616 apparently healthy children, aged 12-59 mo, and 4639 apparently healthy nonpregnant women, aged 15-49 y. We used restricted cubic spline regression models to determine SF thresholds for ID. RESULTS: SF thresholds identified by Hb and eZnPP did not differ significantly in children, 21.2 µg/L (95% confidence interval: 18.5, 26.5) and 18.7 µg/L (17.9, 19.7), and, in women, were similar although significantly different, 24.8 µg/L (23.4, 26.9) and 22.5 µg/L (21.7, 23.3). CONCLUSIONS: These NHANES results suggest that physiologically based SF thresholds are higher than the thresholds from expert opinion established during the same era. SF thresholds found using physiological indicators detect the onset of iron-deficient erythropoiesis, whereas the WHO thresholds identify a later, more severe stage of ID.

Ameloblastoma metastásico / Metastatic ameloblastoma

77REPERT MED CIR. 2023;32(1):77-80Mario Alexander Melo MD*María Camila PiñerosbAna María TorresbFabián Parra F. MDcRafael Baracaldo A. MDda Patología. Grupo de Patología Oncológica, Instituto Nacional de Cancerología, Universidad El Bosque. Bogotá DC, Colombia. b Odontólogía, Patología Oral y Medios Diagnósticos, Universidad El Bosque, Bogotá DC, Colombia. c Radiología e Imágenes Diagnósticas, Fundación Universitaria Sanitas, Bogotá DC, Colombia. d Patología, Fundación Universitaria de Ciencias de la Salud. Bogotá DC, Colombia.Introducción: el ameloblastoma es un tumor epitelial benigno de origen odontogénico, de crecimiento progresivo, caracterizado por expansión ósea y tendencia a la recurrencia local si no se trata en forma adecuada. De acuerdo con las características clínicas y radiográficas se clasifica en ameloblastoma uniquístico, periférico/extraóseo y el metastásico. Presentación del caso: el presente manuscrito se quiere reseñar el caso clínico de un ameloblastoma metastásico, el cual es capaz de producir siembras a pesar de su apariencia histológica benigna. Discusión y conclusiones: las variadas formas clínicas y radiográficas hacen que el ameloblastoma metastásico requiera, desde su diagnóstico inicial, un estudio detallado ya que es importante entender el concepto de esta patología como lesión clínica que realiza metástasis a distancia, pero su comportamiento histológico es benigno

Introduction: ameloblastoma is a benign epithelial odontogenic tumor that progresses slowly and is characterized by bone expansion and tendency for local recurrence if not treated properly. According to the clinical and radiographic characteristics, it is classified as unicystic, peripheral/extraosseous and metastatic ameloblastoma. Case presentation: the present manuscript aims to review the clinical case of a metastatic ameloblastoma, which can metastasize in spite of a benign histological appearance. Discussion and conclusions: the various clinical and radiographic forms of metastatic ameloblastoma require, from its initial diagnosis, a detailed study, since it is important to understand the concept of this clinico-pathological entity as a lesion with distant metastases but benign histological features

Iron Deficiency in the United States: Limitations in Guidelines, Data, and Monitoring of Disparities.

Iron deficiency and the more severe sequela, iron deficiency anemia, are public health problems associated with morbidity and mortality, particularly among pregnant women and younger children. The 1998 Centers for Disease Control and Prevention recommendations for prevention and control of iron deficiency in the United States is old and does not reflect recent evidence but is a foundational reference for many federal, clinical, and program guidelines. Surveillance data for iron deficiency are sparse at all levels, with critical gaps for pregnant women and younger children. Anemia, iron deficiency, and iron deficiency anemia are often conflated but should not be. Clinical guidelines for anemia, iron deficiency, and iron deficiency anemia give inconsistent recommendations, causing nonsystematic assessment of iron deficiency. Screening for iron deficiency typically relies on identifying anemia, despite anemia's low sensitivity for iron deficiency. In the National Health and Nutrition Examination Survey, more than 70% of iron deficiency is missed among pregnant women and children by relying on hemoglobin for iron deficiency screening. To improve assessment and diagnosis and strengthen surveillance, better and more complete data and updated foundational guidance on iron deficiency and anemia are needed that consider new evidence for measuring and interpreting laboratory results. (Am J Public Health. 2022;112(S8):S826-S835. https://doi.org/10.2105/AJPH.2022.306998).

Physiologically based serum ferritin thresholds for iron deficiency in women of reproductive age who are blood donors.

Our objective is to develop a physiologically based method to determine serum ferritin thresholds for iron deficiency in healthy individuals. The current World Health Organization threshold of <15 µg/L for iron deficiency in women is based on expert opinion. We examined the relationship between serum ferritin and 2 independently measured indicators of iron-deficient erythropoiesis, soluble transferrin receptor (sTfR) and hemoglobin, in baseline data from 286 women, 20 to 49 years, who were first-time or reactivated donors in the Retrovirus Epidemiology Donor Study-II Donor Iron Status Evaluation (REDS-RISE) study. At lower serum ferritin concentrations, median sTfR increased as hemoglobin decreased. Using restricted cubic spline regression analysis to determine thresholds for iron-deficient erythropoiesis, the thresholds identified by sTfR (serum ferritin < 25.4 µg/L) and hemoglobin (serum ferritin < 25.3 µg/L) did not differ significantly. The thresholds found in the REDS-RISE study do not differ from those identified by sTfR (serum ferritin < 25.5 µg/L) and hemoglobin (serum ferritin < 26.6 µg/L) in a previous study of 5442 women, 20 to 49 years, in the US National Health and Nutrition Examination Survey 2003 to 2018 (P = .98 and 0.83, respectively). Although international comparisons are needed, these results with US data provide additional evidence for the potential usefulness of a physiologically based method to identify serum ferritin thresholds for iron deficiency.

Factors associated with anaemia in a nationally representative sample of nonpregnant women of reproductive age in Nepal.

We used cross-sectional data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia among a nationally representative sample of nonpregnant women 15- 49 years (n = 1, 918). Haemoglobin, biomarkers of iron status and other micronutrients, infection, inflammation, and blood disorders were assessed from venous blood. Soil-transmitted helminth and Helicobacter pylori infections were assessed from stool. Sociodemographic, household, and health characteristics and diet were ascertained by interview. We conducted bivariate analyses between candidate predictors and anaemia (haemoglobin <12.0 g/ dL, altitude- and smoking-adjusted). Candidate predictors that were significant in bivariate models (P < 0.05) were included in the multivariable logistic regression model, accounting for complex sampling design. Anaemia prevalence was 20.2% (95% confidence interval [CI] [17.6, 22.8]). Associated with reduced anaemia odds were living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.35, 95% CI [0.21, 0.60] and AOR 0.41, 95% CI [0.29, 0.59], respectively), recent cough (AOR 0.56, 95% CI [0.38, 0.82]), hormonal contraceptive use (AOR 0.58; 95% CI [0.38, 0.88]), ln ferritin (micrograms per litre; AOR 0.43, 95% CI [0.35, 0.54]), and ln retinol binding protein (micrograms per litre; AOR 0.20, 95% CI [0.11, 0.37]). Residing in a house with an earth floor (AOR 1.74, 95% CI [1.18, 2.56]), glucose-6- phosphate dehydrogenase deficiency (AOR 2.44, 95% CI [1.66, 3.60]), and haemoglobinopathies (AOR 6.15, 95% CI [3.09, 12.26]) were associated with increased anaemia odds. Interventions that improve micronutrient status, ensure access to hormonal birth control, and replace dirt floors to reduce infection risk might help reduce anaemia in this population.

Factors associated with anaemia among adolescent boys and girls 10-19 years old in Nepal.

We used data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia (World Health Organization cut-points using altitude- and smoking-adjusted haemoglobin [Hb]) among nationally representative samples of adolescents 10-19 years. Hb, biomarkers of micronutrients, infection and inflammation were assessed from venous blood. Sociodemographic and household characteristics, dietary diversity, pica and recent morbidity were ascertained by interview. We explored bivariate relationships between candidate predictors and anaemia among boys (N = 967) and girls (N = 1,680). Candidate predictors with P < 0.05 in bivariate analyses were included in sex-specific multivariable logistic regression models. Anaemia prevalence was 20.6% (95% confidence interval [CI] [17.1, 24.1]) among girls and 10.9% (95% CI [8.2, 13.6]) among boys. Among girls, living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.28, 95% CI [0.15, 0.52] and AOR 0.42, 95% CI [0.25, 0.73], respectively), ln ferritin (µg/L) (AOR 0.53, 95% CI [0.42, 0.68]) and ln retinol binding protein (RBP) (µmol/L) (AOR 0.08, 95% CI [0.04, 0.16]) were associated with reduced anaemia odds. Older age (age in years AOR 1.19, 95% CI [1.12, 1.27]) and Janajati ethnicity relative to the Muslim ethnicity (AOR 3.04, 95% CI [1.10, 8.36]) were associated with higher anaemia odds. Among boys, ln RBP [µmol/L] (AOR 0.25, 95% CI [0.10, 0.65]) and having consumed flesh foods (AOR 0.57, 95% CI [0.33, 0.99]) were associated with lower anaemia odds. Open defecation (AOR 2.36, 95% CI [1.15, 4.84]) and ln transferrin receptor [mg/L] (AOR 3.21, 95% CI [1.25, 8.23]) were associated with increased anaemia odds. Anaemia among adolescents might be addressed through effective public health policy and programs targeting micronutrient status, diet and sanitation.

Left ventricular assist device implants in patients on extracorporeal membrane oxygenation: do we need cardiopulmonary bypass?

OBJECTIVES: Implanting a durable left ventricular assist device (LVAD) in a patient on extracorporeal life support (ECLS) is challenging. The goal of this study was to compare the results of patients from a European registry who had a durable LVAD implanted with or without transition from ECLS to cardiopulmonary bypass (CPB). METHODS: A total of 531 patients on ECLS support who had an LVAD implant between January 2010 and August 2018 were analysed; after 1:1 propensity score matching, we identified and compared 175 patients in each group. RESULTS: The duration of preoperative ECLS was 7 [standard deviation (SD) 6] vs 7 (SD 6) days in patients with or without CPB (P = 0.984). The surgical time was longer in the CPB group [285 (SD 72) vs 209 [SD 75] min; P ≤ 0.001). The postoperative chest tube output was comparable [1513 (SD 1311) vs 1390 (SD 1121) ml; P = 0.3]. However, re-exploration for bleeding was necessary in 41% vs 29% of patients with or without CPB (P = 0.01) and a significantly higher number of packed red blood cells and fresh frozen plasma [8 (SD 8) vs 6 (SD 4) units; P = 0.001 and 6 (SD 7) vs 5 (SD 5) units; P = 0.03] were administered to patients operated on with CPB. A postoperative mechanical right ventricular support device was necessary in 50% vs 41% of patients (P = 0.08). The stroke rate was not significantly different (P 0.99). No difference in survival was observed. CONCLUSIONS: Omitting CPB for an LVAD implant in patients on ECLS is safe and results in shorter operating time, less re-exploration for bleeding and fewer blood products. However, no survival benefit is observed.

Presencia de inestabilidad microsatélite en pacientes colombianos con adenocarcinoma colorrectal / Microsatellite instability in Colombian patients with colorectal adenocarcinoma

Resumen Introducción y objetivos: la vía de inestabilidad de microsatélites (IMS) está implicada en la carcinogénesis de un 15 % de carcinomas colorrectales (CCR). La detección de esta alteración tiene relevancia en el pronóstico y en el tratamiento de los pacientes con CCR. El objetivo del presente estudio es determinar la prevalencia de IMS en CCR en una cohorte de pacientes de Bogotá, Colombia. Materiales y métodos: se evaluó por inmunohistoquímica la presencia de homólogo MutL 1 (MLH1), segregación posmeiótica aumentada 2 (PMS2), homólogo mutS 2 (MSH2) y homólogo mutS 6 (MSH6) en muestras de CCR prevenientes de colectomías. Adicionalmente, se analizaron las variables clinicopatológicas. A los casos con pérdida de MLH1 y PMS2 se les evaluó la mutación del gen BRAF. Resultados: en total se incluyeron 86 casos. La mediana de edad de los pacientes con CCR fue de 69 años, 52,3 % fueron hombres. De los pacientes con CCR, 12 (13,9 %) presentaron IMS, de los cuales 10 (83,3 %) tenían ausencia de expresión MLH1/PMS2 y 2 (16,7 %), de MSH2/MSH6. La mediana de edad de los pacientes con CCR e IMS fue de 52 años (45-76,5), 9 eran hombres y el 66,7 % de estos casos se localizaron en el colon derecho. El tipo histológico más frecuente fue adenocarcinoma moderadamente diferenciado (67 %). Los linfocitos infiltrantes al tumor fueron observados en el 83 %, la presencia de infiltrado de tipo Crohn estaba presente en el 42 %. La mutación de BRAF se observó en el 30 % de los pacientes con pérdida de MLH1 y PMS2. Conclusión: la prevalencia de la IMS en nuestra población fue de 14 %, datos similares a los observados en la población norteamericana y europea. Sin embargo, se observa que el 83 % presentó pérdida de expresión del complejo MLH1/PMS2, una prevalencia mayor comparada con otras poblaciones.

Abstract Introduction: The microsatellite instability (MSI) pathway is involved in the carcinogenesis of 15% of colorectal carcinomas (CRC). The detection of this alteration is relevant for the prognosis and treatment of CRC patients. Objective: The aim of this study is to determine the prevalence of MSI in CRC in a cohort of patients in Bogotá, Colombia. Materials and methods: The presence of MLH1, PMS2, MSH2, and MSH6 was evaluated by immunohistochemistry in CRC samples collected during colectomy. Clinicopathological variables were analyzed as well. Cases with loss of MLH1 and PMS2 were evaluated for BRAF gene mutation. Results: A total of 86 cases were included. The median age was 69 years, 52.3% were male. 12 (13.9%) patients had IMS, 10 (83.3%) had absence of MLH1/PMS2 expression and 2 (16.7%) absence of MSH2/MSH6 expression. The median age of patients with IMS was 52 years (45-76.5), of which 9 were male. 66.7% of carcinomas were located in the right colon and the most frequent histological type was moderately differentiated adenocarcinoma (67%). Tumor infiltrating lymphocytes were observed in 83% of the cases, while the presence of Crohn's-like infiltrate was present in 42%. BRAF mutation was observed in 30% of patients with loss of MLH1 and PMS2. Conclusion: The prevalence of IMS in our population was 14%, similar to the data observed in the North American and European populations. However, we observed that 83% had loss of expression of the MLH1/PMS2 complex, a higher prevalence compared to other populations.

Physiologically based serum ferritin thresholds for iron deficiency in children and non-pregnant women: a US National Health and Nutrition Examination Surveys (NHANES) serial cross-sectional study.

BACKGROUND: Serum ferritin concentrations are the most widely used indicator for iron deficiency. WHO determined that insufficient data are available to revise the serum ferritin thresholds of less than 12 µg/L for children and less than 15 µg/L for women, which were developed on the basis of expert opinion, to define iron deficiency. We aimed to derive new physiologically based serum ferritin concentration thresholds for iron deficiency in healthy young children and non-pregnant women using data from the US National Health and Nutrition Examination Survey (NHANES). METHODS: In this serial cross-sectional study, we examined the relationship of serum ferritin with two independent indicators of iron-deficient erythropoiesis, haemoglobin and soluble transferrin receptor (sTfR), in children (12-59 months) and non-pregnant women (15-49 years) using cross-sectional NHANES data from 2003-06, 2007-10, and 2015-18. NHANES is a US national stratified multistage probability sample that includes a household interview followed by a standardised physical examination in a mobile examination centre. We excluded individuals with missing serum ferritin, sTfR, haemoglobin, or white blood cell counts measurements; non-pregnant women with missing C-reactive protein (CRP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) data were also excluded. In addition, individuals with infection (white blood cell counts >10·0×109/L) and non-pregnant women with possible liver disease (ALT >70 IU/L or AST >70 IU/L) and inflammation (CRP >5·0 mg/L) were excluded. We examined distributions of haemoglobin and sTfR with serum ferritin and used restricted cubic spline regression models to determine serum ferritin thresholds for iron-deficient erythropoiesis. FINDINGS: 5964 children and 10 462 non-pregnant women had physical examinations and were screened for inclusion in the study, of whom 2569 (43·1%) children and 7498 (71·7%) non-pregnant women were included. At lower serum ferritin concentrations, median haemoglobin concentration decreased as sTfR concentration increased, with each varying in a curvilinear manner. Using restricted cubic spline plateau points to determine the onset of iron-deficient erythropoiesis, the serum ferritin thresholds identified by haemoglobin and sTfR concentrations were not different. For children, the haemoglobin identified serum ferritin threshold was 19·9 µg/L (95% CI 18·8-22·6) and the sTfR identified serum ferritin threshold was 20·0 µg/L (19·4-20·9; p=0·89). For women the haemoglobin identified serum ferritin threshold was 25·2 µg/L (24·2-26·2) and the sTfR identified serum ferritin threshold was 24·0 µg/L (23·3-24·6; p=0·05). INTERPRETATION: The association between two independent indicators of iron-deficient erythropoiesis, haemoglobin and sTfR, identified serum ferritin concentration thresholds of about 20 µg/L for children and 25 µg/L for non-pregnant women, providing physiological evidence of potential new thresholds for consideration when determining the prevalence and distribution of iron deficiency in populations. In healthy children and non-pregnant women, physiologically based thresholds for iron deficiency might be more clinically and epidemiologically relevant than those based on expert opinion. Validation of this physiologically based approach in non-US populations might help the international harmonisation of serum ferritin thresholds for iron deficiency. FUNDING: None.

Introducción al dossier

Resumen Introducción al dossier

Abstract Dossier introduction

Impact of extra-corporeal life support (ECLS) cannulation strategy on outcome after durable mechanical circulation support system implantation on behalf of durable MCS after ECLS Study Group.

BACKGROUND: The literature on outcomes of patients requiring durable mechanical circulatory support (MCS) after extra-corporeal life support (ECLS) is limited. The aim of this study was to investigate the impact of preoperative ECLS cannulation on postoperative outcome after durable MCS implantation. METHODS: The durable MCS after ECLS registry is a multicenter retrospective study that gathered data on consecutive patients who underwent durable MCS implantation after ECLS between January 2010 and August 2018 in eleven high volume European centers. Patients who underwent the implantation of total artificial heart, pulsatile pumps, or first-generation pumps after ECLS were excluded from the analysis. The remaining patients were divided into two groups; central ECLS group (cECLS) and peripheral ECLS group (pECLS). A 1:1 propensity score analysis was performed to identify two matched groups. The outcome of these two groups was compared. RESULTS: A total of 531 durable MCS after ECLS were implanted during this period. The ECLS cannulation site was peripheral in 87% (n=462) and central in 13% (n=69) of the patients. After excluding pulsatile pumps and total artificial heart patients, a total of 494 patients remained (pECLS =434 patients, cECLS =60 patients). A 1:1 propensity score analysis resulted in 2 matched groups (each 55 patients) with median age of 54 years (48-60 years) in cECLS group and 54 years (43-60 years) in pECLS group. HeartWare HVAD (Medtronic, Minneapolis, MN) was implanted in the majority of the patients (cECLS =71% vs. pECLS =76%, P=0.67). All postoperative morbidities were comparable between the groups. The thirty-day, one year and long-term survival was comparable between the groups (P=0.73). CONCLUSIONS: The cannulation strategy of ECLS appears to have no impact on the post-operative outcome after durable MCS implantation.

p97 and p47 function in membrane tethering in cooperation with FTCD during mitotic Golgi reassembly.

p97ATPase-mediated membrane fusion is required for the biogenesis of the Golgi complex. p97 and its cofactor p47 function in soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) priming, but the tethering complex for p97/p47-mediated membrane fusion remains unknown. In this study, we identified formiminotransferase cyclodeaminase (FTCD) as a novel p47-binding protein. FTCD mainly localizes to the Golgi complex and binds to either p47 or p97 via its association with their polyglutamate motifs. FTCD functions in p97/p47-mediated Golgi reassembly at mitosis in vivo and in vitro via its binding to p47 and to p97. We also showed that FTCD, p47, and p97 form a big FTCD-p97/p47-FTCD tethering complex. In vivo tethering assay revealed that FTCD that was designed to localize to mitochondria caused mitochondria aggregation at mitosis by forming a complex with endogenous p97 and p47, which support a role for FTCD in tethering biological membranes in cooperation with the p97/p47 complex. Therefore, FTCD is thought to act as a tethering factor by forming the FTCD-p97/p47-FTCD complex in p97/p47-mediated Golgi membrane fusion.

Impact of a surgical approach for implantation of durable left ventricular assist devices in patients on extracorporeal life support.

BACKGROUND: The aim of this study was to evaluate the impact of the surgical approach on the postoperative outcome in patients who underwent left ventricular assist device (LVAD) implantation after having received veno-arterial extracorporeal life support (va-ECLS) using data from a European registry (ECLS-VAD). Five hundred and thirty-one patients were included. METHODS: A propensity score-adjusted outcome analysis was performed, resulting in 324 patients in the full sternotomy (FS) group and 39 in the less invasive surgery (LIS) group. RESULTS: The surgery lasted in median 236 min in the FS group versus 263 min in the LIS group (p = 0.289). The median chest tube output during the first 24 h was similar in both groups. Patients who underwent implantation with an FS required more blood products during the first 24 postoperative hours (median 16 vs. 12, p = 0.033). The incidence of revision due to bleeding was also higher (35.5 vs. 15.4%, p = 0.016). A temporary postoperative right ventricular assist device was necessary in 45.1 (FS) versus 23.1% (LIS) of patients, respectively (p = 0.067). No stroke occurred in the LIS group during the first 30 days after surgery (7.4% in the FS group). The incidence of stroke and of renal, hepatic, and respiratory failure during the follow-up was similar in both groups. The 30-day and one-year survival were similar in both groups. CONCLUSION: LIS for implantation of a durable LVAD in patients on va-ECLS implanted for cardiogenic shock is associated with less revision due to bleeding, less administration of blood products and absence of perioperative stroke, with no impact on survival.