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Abstract Background The prevalence of teenage pregnancy in Colombia is higher than the worldwide average. The identification of socio-geographical disparities might help to prioritize public health interventions. Aim To describe variation in the probability of teenage maternity across geopolitical departments and socio-geographical intersectional strata in Colombia. Methods A cross-sectional study based on live birth certificates in Colombia. Teenage maternity was defined as a woman giving birth aged 19 or younger. Multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was applied using multilevel Poisson and logistic regression. Two different approaches were used: (1) intersectional: using strata defined by the combination of health insurance, region, area of residency, and ethnicity as the second level (2) geographical: using geopolitical departments as the second level. Null, partial, and full models were obtained. General contextual effect (GCE) based on the variance partition coefficient (VPC) was considered as the measure of disparity. Proportional change in variance (PCV) was used to identify the contribution of each variable to the between-strata variation and to identify whether this variation, if any, was due to additive or interaction effects. Residuals were used to identify strata with potential higher-order interactions. Results The prevalence of teenage mothers in Colombia was 18.30% (95% CI 18.20–18.40). The highest prevalence was observed in Vichada, 25.65% (95% CI: 23.71–27.78), and in the stratum containing mothers with Subsidized/Unaffiliated healthcare insurance, Mestizo, Rural area in the Caribbean region, 29.08% (95% CI 28.55–29.61). The VPC from the null model was 1.70% and 9.16% using the geographical and socio-geographical intersectional approaches, respectively. The higher PCV for the intersectional model was attributed to health insurance. Positive and negative interactions of effects were observed. Conclusion Disparities were observed between intersectional socio-geographical strata but not between geo-political departments. Our results indicate that if resources for prevention are limited, using an intersectional socio-geographical approach would be more effective than focusing on geopolitical departments especially when focusing resources on those groups which show the highest prevalence. MAIHDA could potentially be applied to many other health outcomes where resource decisions must be made.

ABSTRACTObjective Reducing maternal morbidity and mortality has been a challenge for low and middle-income countries, especially in the setting of hypertensive disorders of pregnancy. Improved strategies for treating obstetric patients with resistant hypertension are needed. We sought to explore whether hemodynamic parameters may be used to identify patients that develop resistant hypertension in pregnancy.Methods Retrospective cohort study among pregnant patients with gestational hypertension or preeclampsia that experienced severe blood pressure elevations. Hemodynamic variables were evaluated, including cardiac output (CO), and total peripheral resistance (TPR). The primary endpoint was resistant hypertension. An exploratory logistic regression was performed to evaluate the association between the hemodynamic profile and the development of resistant hypertension. Adverse maternal and fetal outcomes were additionally described according to the presence of resistant hypertension.Results Fifty-seven patients with severe pregnancy hypertension were included, of whom 34 developed resistant hypertension (59.7%). The resistant hypertension group, in comparison to those without resistant hypertension, presented with a hypodynamic profile characterized by reduced CO 1400 dyn-s/cm5 (64.7% vs. 39.1%, p: 0.057). Logistic regression analysis revealed an association between a hypodynamic profile and resistant hypertension (OR 3.252, 95% CI 1.079–9.804; p = 0.035). Newborns of the resistant hypertension group had more frequent low birth weight (

AimThis study aimed to assess the cardiometabolic sex similarities and differences in adults born small for gestational age.MethodsThis study was an ambispective cohort study from a birth registry in Barcelona, Spain, including 523 adult participants (20–40 years-old) subdivided as born small for gestational age (SGA, if birth weight

Global cervical cancer incidence and mortality have remained a major public health problem. Depending on the quality and coverage of preventive programs, and the capacity of health care systems, different screening tests are used, with the Pap smear being the most widely implemented. Several difficulties have been reported in accessing timely detection, causing late cervical cancer diagnosis. Trying to close these gaps, new screening devices have been developed in recent years; however, there is a lack of knowledge about whether or not women perspective has been included in the design process and technological development of these devices. This scoping review aimed to describe and synthesize scientific literature on women's critical experiences with Pap smears to prospectively contribute to the design, development, and scale-up of cervical cancer screening devices. The electronic databases Web of Science, Scopus, PubMed, PsycINFO and SciELO were searched for relevant studies published between 2012 and 2021; finally, 18 qualitative studies were included. Experiences were classified into four categories: fear and embarrassment, speculum pain and discomfort, outcome distress and health service barriers. Critical experiences before, during, and after the test were analyzed in turn. In particular, during the test, women reported pain associated with the use of the speculum. The acceptability of new screening devices will largely depend on comfort during the test and timely delivery of results. This review provides a useful qualitative synthesis, not only to advance the design of novel devices but also for future implementation research in cervical screening services.

Abstract Background Healthcare Workers (HCW) are repeatedly exposed to SARS-CoV-2 infection. The aim of this study was to identify factors associated with SARS-CoV-2 infection among HCW in one of the largest cities in Colombia. Methods We conducted a case–control study, where cases had a positive reverse transcription-polymerase chain reaction and controls had a negative result. Participants were randomly selected and interviewed by phone. Analyses were performed using logistic regression models. Results A total of 110 cases and 113 controls were included. Men (AdjOR 4.13 95% CI 1.70–10.05), Nurses (AdjOR 11.24 95% CI 1.05–119.63), not using a high-performance filtering mask (AdjOR 2.27 95% CI 1.02–5.05) and inadequate use of personal protective equipment (AdjOR 4.82 95% CI 1.18–19.65) were identified as risk factors. Conversely, graduate (AdjOR 0.06 95% CI 0.01–0.53) and postgraduate (AdjOR 0.05 95% CI 0.005–0.7) education, feeling scared or nervous (AdjOR 0.45 95% CI 0.22–0.91), not always wearing any gloves, caps and goggles/face shields (AdjOR 0.10 95% CI 0.02–0.41), and the use of high-performance filtering or a combination of fabric plus surgical mask (AdjOR 0.27 95% CI 0.09–0.80) outside the workplace were protective factors. Conclusion This study highlights the protection provided by high-performance filtering masks or double masking among HCW. Modifiable and non-modifiable factors and the difficulty of wearing other protective equipment needs to be considered in designing, implementing and monitoring COVID-19 biosafety protocols for HCW.

The nutrition of the plant has an important function in the appearance and susceptibility of the crop. The present work intends an analysis of the state of the art regarding of the effect of the mineral nutrition, in particular the primary macroelements about the susceptibility to diseases. The revision behaved by means of the study of original scientific articles and bibliographical revisions, published in Cuban and foreigners; as well as the works carried out as thesis in universities of the region and of the world. Although there are some contradictions, the primary macroelements can affect tolerance and / or resistance to plant diseases caused by various pathogens. The most observed effect is the decrease in the symptoms of the disease except for the nitrogen, the one which in excess or deficit leads to higher incidence in the increase of susceptibility. An appropriate supply of the fertilization that promotes the good growth of the plants is an element to consider for the resistance to diseases.

The evaluation of diseases resistance is a key step in the Sugarcane Breeding Program. For this reason, it is necessary the updating of the methodologies established for this purpose. The objective of this work was to compare the current methodology and the use of linear regression for the classification of cultivars by their reaction to the sugarcane mosaic disease. Data from a multi-environmental study conducted at the three Test Centers: Jovellanos, Florida and Mayarí, were used. Thirteen sugarcane cultivars were included. The results showed variability in the magnitude of the expected response of the control, which prevented the validation of the six trials evaluated by the current methodology and, therefore, the classification of the material under study. However, the application of the comparison of means between the infection percentages of the control cultivars offered an alternative for the revalidation of the studies. In addition, the application of linear regression allowed obtaining mathematical models for the assignment of a rate and reaction category against the mosaic to the cultivars in the studies, which gives them greater precision in the results.

Objective To describe a novel strategy, Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) to evaluate hospital performance, by analysing differences in 30-day mortality after a first-ever acute myocardial infarction (AMI) in Sweden.Design Cross-classified study.Setting 68 Swedish hospitals.Participants 43 247 patients admitted between 2007 and 2009, with a first-ever AMI.Primary and secondary outcome measures We evaluate hospital performance by analysing differences in 30-day mortality after a first-ever AMI using a cross-classified multilevel analysis. We classified the patients into 10 categories according to a risk score (RS) for 30-day mortality and created 680 strata defined by combining hospital and RS categories.Results In the cross-classified multilevel analysis the overall RS adjusted hospital 30-day mortality in Sweden was 4.78% and the between-hospital variation was very small (variance partition coefficient (VPC)=0.70%, area under the curve (AUC)=0.54). The benchmark value was therefore achieved by all hospitals. However, as expected, there were large differences between the RS categories (VPC=34.13%, AUC=0.77)Conclusions MAIHDA is a useful tool to evaluate hospital performance. The benefit of this novel approach to adjusting for patient RS is that it allowed one to estimate separate VPCs and AUC statistics to simultaneously evaluate the influence of RS categories and hospital differences on mortality. At the time of our analysis, all hospitals in Sweden were performing homogeneously well. That is, the benchmark target for 30-day mortality was fully achieved and there were not relevant hospital differences. Therefore, possible quality interventions should be universal and oriented to maintain the high hospital quality of care.

Objectives. To determine the profiles of highly frequent users of primary care services and the associations of these profiles with depressive anxiety disorders in Cali, Colombia. Materials and Methods. A case-control study, high-frequency cases were defined as those involving patients with a percentile 75 with regard to the frequency of spontaneous use of outpatient facilities in the last 12 months; controls were defined as those with a percentile 25. A multiple correspondence analysis was used to describe patient profiles, and the influences of depression and anxiety on frequent attendance was determined via logistic regression. Results. Among the 780 participating patients, differences in the profiles among frequent users and controls were related to predisposing factors such as sex, age, and education, capacity factors such as the time required to visit the institution and the means of transport used, and need factors such as health perceptions, social support, family function, and the presence of anxiety or depressive disorders. A depression or anxiety disorder was found to associate positively with frequent attendance (adjusted odds ratio [aOR]: 1.99, 95% confidence interval [CI]: 1.19–3.31) and a referral system (aOR: 1.61, 95% CI: 1.01–2.76), but negatively with mild or no family dysfunction (aOR: 0.79; 95% CI: 0.48–0.88) after adjusting for age, sex, ethnicity, and health service-providing institutions. Conclusions. The profiles of high-frequency patients differ from control patients with respect to factors related to capacity, need, and willingness; in particular, the latter were independently associated with frequent attendance. Notably, the presence of an anxious or depressive disorder doubled the risk of highfrequency attendance at a primary care facility.

RESUMEN Objetivo: determinar la prevalencia y los factores relacionados con la adherencia no farmacológica en pacientes con hipertensión arterial (hta) y diabetes mellitus (dm). Metodología: estudio observacional transversal en pacientes adultos mayores de 35 años con diagnóstico de hta o dm, atendidos en un programa de Renoprotección en cuidado primario en Cali, Colombia. Se excluyeron aquellos pacientes con enfermedad renal crónica en estadío kdoqi 4-5, los que presentaran comorbilidades adicionales que deterioraran la función renal o con trastornos neuropsiquiátricos diagnosticados previamente. La adherencia no farmacológica se determinó mediante un cuestionario de autoreporte y los factores asociados a la misma se determinaron mediante regresión de Poisson con varianza robusta. Resultados: la prevalencia de la adherencia no farmacológica fue de 9,4%. La inactividad física estuvo presente en 75% de los pacientes, y más del 19% de la población consumía sal frecuentemente. Entre los diabéticos, 18% consumía carbohidratos con frecuencia. Los hombres mostraron ser menos adherentes que las mujeres (RP: 0,21; p = 0,002). Los factores asociados estar estudiando, desempleado o pensionado (RP: 4,42; p = 0,019), recibir apoyo del equipo de salud (RP: 3,17; p = 0,032), tener diagnóstico de diabetes (RP: 7,79; p = 0,000) y la función renal en KDOQI-3 (RP: 5,14; p = 0,008). Conclusión: la adherencia no farmacológica fue muy baja en la población de estudio, en particular en relación con la inactividad física. Los factores asociados positivamente a la adherencia fueron el sexo femenino, tener una ocupación diferente al hogar, diagnostico de diabetes, enfermedad renal en KDOQI-3 y contar con apoyo del equipo de salud. / ABSTRACT Objective: to analyze avoidable mortality between 1998 and 2007 in the border states of Northern Mexico to evaluate, indirectly, the quality of the region's health care services. Methodology: the information on mortality provided by the National Health Information System (sinais) was analyzed. The unit of analysis was the basic cause of death. The cause was coded in accordance with the ICD-10.Avoidable mortality was classified according to Gomez’s death causes catalog. Likewise, an exploratory analysis was conducted which focused on the relationship between avoidable mortality and eligibility and the socioeconomic level of the municipalities in which the deaths took place. Results: the global rate of avoidable mortality was of 350.2 deaths per 1000 inhabitants in the region. the rates of avoidable mortality by early diagnosis and medical treatment, violence, and HIV/AIDS were 223, 60 and 5 per 1000 inhabitants respectively. These causes of avoidable mortality showed variations between states in terms of magnitude, eligibility and socio-demographic characteristics. Discussion and conclusions: the population living in the states located in the northern border of Mexico have a very intense epidemiological and sociodemographical dynamics. The results of this study suggest that the Mexican health system is being overcome by the high frequency of noncommunicable diseases in this region. In social terms, Mexico has structural conditions that facilitate the development of illegal drugs traffic through the Northern states of Mexico. This could be related to the frequency of violent avoidable deaths and, in a subsidiary manner, in HIV/AIDS deaths.

BACKGROUND:Preeclampsia (PE) is associated with a high risk of perinatal morbidity and mortality. However, there is no consensus in the definition of high-risk women. AIM:To question current definition of high PE risk and propose a definition that considers individual heterogeneity to improves risk classification. METHODS:A stratified analysis by parity was conducted using the Swedish Birth Register between 2002-2010 including 626.600 pregnancies. The discriminatory accuracy (DA) of traditional definitions of high-risk women was compared with a new definition based on 1) specific combinations of individual variables and 2) a centile cut-off of the probability of PE predicted by a multiple logistic regression model. RESULTS:None of the classical risk-factors alone reached an acceptable DA. In multiparous, any combination of a risk-factor with previous PE or HBP reached a +LR>10. The combination of obesity and multiple pregnancy reached a good DA particularly in the presence of previous preeclampsia (positive likelihood ratio (LR+) = 26.5 or chronic hypertension (HBP) LR+ = 40.5. In primiparous, a LR+>15 was observed in multiple pregnancies with the simultaneous presence of obesity and diabetes mellitus or with HBP. Predicted probabilities above 97 centile in multiparous and 99 centile in primiparous provided high (LR+ = 12.5), and moderate (LR+ = 5.85), respectively. No one risk factor alone or in combination provided a LR- sufficiently low to rule-out the disease. CONCLUSIONS:In preeclampsia prediction the combination of specific risk factors provided a better discriminatory accuracy than traditional single risk approach. Our results contribute to a more personalized risk estimation of preeclampsia.

El presente trabajo muestra el proceso metodológico llevado a cabo para lograr un acercamiento a la cuantificación de la información arqueológica, mediante la sistematización de los datos para su volcado en el Sistema de Información Patrimonial de Guadix (SIPAG). Se ha analizado la documentación de un total de 58 intervenciones arqueológicas urbanas llevadas a cabo desde el año 1986 hasta el 2009. Dentro de la información arqueológica encontramos diferentes tipos de datos gráficos y alfanuméricos, como planimetrías, fotografías, croquis, memorias de excavación, libros diarios o fichas de registro. La disponibilidad de estos tipos de datos es esencial para la recuperación, homogeneización y sistematización de la información, así como para la investigación, gestión y difusión del patrimonio arqueológico de un lugar. Muchas de esas intervenciones presentan una considerable falta de información, ya sea por disponibilidad o por inexistencia, lo que complica la recuperación y conocimiento de los restos. Por ello hemos creado una metodología que nos ayude a cuantificar la pérdida de información arqueológica de forma individualizada para cada intervención y de forma general respecto al yacimiento, estableciendo posteriormente niveles de aplicabilidad a la investigación, a la gestión y a la difusión.

Objective: this study’s goal was to determine the most prevalent mental disorders and the impact on the perception of disability and suicidal ideation among the population from a primary health care center in the city of Cali. Methodology: a cross sectional study was conducted on 254 patients who were screened with the prime-md instrument. Descriptive statistics was used in the analysis to determine the most frequent disorders. Similarly, a multiple analysis with logistic and Poisson regressions using robust variance was conducted to determine the influence of mental disorders on disability and suicidal ideation. Results: most patients were female, young, and mature adults. Depression was present in 66.8% of all cases, followed by somatization disorder and anxiety. Half of the patients had had suicidal ideations at some point in their lives, and three out of four patients claimed to suffer from some kind of disability. Upon adjusting for the covariables, depression and anxiety disorders had a strong association with suicidal ideation and perceived disability that was overestimated by the logistic regression. Conclusion: depression and anxiety were the most common disorders and showed a strong association with suicidal ideation and disability. This is why it is necessary to screen for those disorders among adults using primary health care services. Likewise, we suggest considering Poisson regression with robust variance in cross-sectional studies in health services.

Objetivos. Se llevó a cabo un estudio retrospectivo con todos los pacientes sometidos a cirugía bariátrica en una institución de salud del régimen contributivo en la ciudad de Cali, con el objetivo de describir dos procedimientos quirúrgicos: la manga gástrica y la derivación gástrica por laparoscopia, en cuanto al control de peso, la tensión arterial, la tasa de filtración glomerular y las complicaciones. Resultados. La manga gástrica requirió un menor tiempo quirúrgico y las complicaciones posoperatorias ocurrieron en 2,35 % de los pacientes frente a 9,79 % en la derivación gástrica. La pérdida del exceso de peso fue casi del 80 % en la muestra y similar entre ambos procedimientos, y ocurrió fundamentalmente en los primeros tres meses después de la cirugía. La presión arterial diastólica logró controlarse antes que la sistólica y al sexto mes se lograron reducir en 8 mm Hg y 10 mm Hg, respectivamente. La tendencia a la reducción fue estadísticamente significativa en el primer y segundo control [coeficiente: -1,9 mm Hg (IC95%: -2,8 a -1,1)] para la presión sistólica y para la diastólica [coeficiente: -1,7 mm Hg (IC95%: -2,3 a -1,1)]. No se observaron cambios significativos en la filtración glomerular. Conclusiones. Los procedimientos bariátricos lograron reducciones exitosas del exceso de peso y tuvieron un impacto en el control de la tensión arterial durante el primer año posquirúrgico, siendo la manga gástrica, en nuestro medio, una técnica tan segura como la derivación gástrica. Se necesitan evaluaciones posteriores para determinar el impacto sobre la tasa de filtración glomerular.

Objetivos. Se llevó a cabo un estudio retrospectivo con todos los pacientes sometidos a cirugía bariátrica en una institución de salud del régimen contributivo en la ciudad de Cali, con el objetivo de describir dos procedimientos quirúrgicos: la manga gástrica y la derivación gástrica por laparoscopia, en cuanto al control de peso, la tensión arterial, la tasa de filtración glomerular y las complicaciones. Resultados. La manga gástrica requirió un menor tiempo quirúrgico y las complicaciones posoperatorias ocurrieron en 2,35 % de los pacientes frente a 9,79 % en la derivación gástrica. La pérdida del exceso de peso fue casi del 80 % en la muestra y similar entre ambos procedimientos, y ocurrió fundamentalmente en los primeros tres meses después de la cirugía. La presión arterial diastólica logró controlarse antes que la sistólica y al sexto mes se lograron reducir en 8 mm Hg y 10 mm Hg, respectivamente. La tendencia a la reducción fue estadísticamente significativa en el primer y segundo control [coeficiente: -1,9 mm Hg (IC95%: -2,8 a -1,1)] para la presión sistólica y para la diastólica [coeficiente: -1,7 mm Hg (IC95%: -2,3 a -1,1)]. No se observaron cambios significativos en la filtración glomerular. Conclusiones. Los procedimientos bariátricos lograron reducciones exitosas del exceso de peso y tuvieron un impacto en el control de la tensión arterial durante el primer año posquirúrgico, siendo la manga gástrica, en nuestro medio, una técnica tan segura como la derivación gástrica. Se necesitan evaluaciones posteriores para determinar el impacto sobre la tasa de filtración glomerular.

Background and Objectives: Our Phase-I parallel-cohort study suggested that managing severe traumatic brain injury (sTBI) in the absence of intracranial pressure (ICP) monitoring using an ad hoc Imaging and Clinical Examination (ICE) treatment protocol was associated with superior outcome vs nonprotocolized management but could not differentiate the influence of protocolization from that of the specific protocol. Phase II investigates whether adopting the Consensus REVised Imaging and Clinical Examination (CREVICE) protocol improved outcome directly or indirectly via protocolization., Methods: We performed a Phase-II sequential parallel-cohort study examining adoption of the CREVICE protocol from no protocol vs a previous protocol in patients with sTBI older than 13 years presenting ≤24 hours after injury. Primary outcome was prespecified 6-month recovery. The study was done mostly at public South American centers managing sTBI without ICP monitoring. Fourteen Phase-I nonprotocol centers and 5 Phase-I protocol centers adopted CREVICE. Data were analyzed using generalized estimating equation regression adjusting for demographic imbalances., Results: A total of 501 patients (86% male, mean age 35.4 years) enrolled; 81% had 6 months of follow-up. Adopting CREVICE from no protocol was associated with significantly superior results for overall 6-month extended Glasgow Outcome Score (GOSE) (protocol effect = 0.53 [0.11, 0.95], P = .013), mortality (36% vs 21%, HR = 0.59 [0.46, 0.76], P < .001), and orientation (Galveston Orientation and Amnesia Test discharge protocol effect = 10.9 [6.0, 15.8], P < .001, 6-month protocol effect = 11.4 [4.1, 18.6], P < .005). Adopting CREVICE from ICE was associated with significant benefits to GOSE (protocol effect = 0.51 [0.04, 0.98], P = .033), 6-month mortality (25% vs 18%, HR = 0.55 [0.39, 0.77], P < .001), and orientation (Galveston Orientation and Amnesia Test 6-month protocol effect = 9.2 [3.6, 14.7], P = .004). Comparing both groups using CREVICE, those who had used ICE previously had significantly better GOSE (protocol effect = 1.15 [0.09, 2.20], P = .033)., Conclusion: Centers managing adult sTBI without ICP monitoring should strongly consider protocolization through adopting/adapting the CREVICE protocol. Protocolization is indirectly supported at sTBI centers regardless of resource availability., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Most patients with severe traumatic brain injury (sTBI) in low- or-middle-income countries and surprisingly many in high-income countries are managed without intracranial pressure (ICP) monitoring. The impact of the first published protocol (Imaging and Clinical Examination [ICE] protocol) is untested against nonprotocol management., Objective: To determine whether patients treated in intensive care units (ICUs) using the ICE protocol have lower mortality and better neurobehavioral functioning than those treated in ICUs using no protocol., Methods: This study involved nineteen mostly public South American hospitals. This is a prospective cohort study, enrolling patients older than 13 years with sTBI presenting within 24 h of injury (January 2014-July 2015) with 6-mo postinjury follow-up. Five hospitals treated all sTBI cases using the ICE protocol; 14 used no protocol. Primary outcome was prespecified composite of mortality, orientation, functional outcome, and neuropsychological measures., Results: A total of 414 patients (89% male, mean age 34.8 years) enrolled; 81% had 6 months of follow-up. All participants included in composite outcome analysis: average percentile (SD) = 46.8 (24.0) nonprotocol, 56.9 (24.5) protocol. Generalized estimating equation (GEE) used to account for center effects (confounder-adjusted difference [95% CI] = 12.2 [4.6, 19.8], P = .002). Kaplan-Meier 6-month mortality (95% CI) = 36% (30%, 43%) nonprotocol, 25% (19%, 31%) protocol (GEE and confounder-adjusted hazard ratio [95% CI] = .69 [.43, 1.10], P = .118). Six-month Extended Glasgow Outcome Scale for 332 participants: average Extended Glasgow Outcome Scale score (SD) = 3.6 (2.6) nonprotocol, 4.7 (2.8) protocol (GEE and confounder-adjusted and lost to follow-up-adjusted difference [95% CI] = 1.36 [.55, 2.17], P = .001)., Conclusion: ICUs managing patients with sTBI using the ICE protocol had better functional outcome than those not using a protocol. ICUs treating patients with sTBI without ICP monitoring should consider protocolization. The ICE protocol, tested here and previously, is 1 option., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

The hyalinizing trabecular adenoma/tumor is a rare and poorly characterized follicular-derived thyroid neoplasm recently shown to harbor recurrent PAX8-GLIS1 or PAX8-GLIS3 gene fusions. Here we sought to define the repertoire of genetic alterations of hyalinizing trabecular tumors, and whether PAX8-GLIS3 fusions are pathognomonic for hyalinizing trabecular tumors. A discovery series of eight hyalinizing trabecular tumors was subjected to RNA-sequencing (n = 8), whole-exome sequencing (n = 3) or targeted massively parallel sequencing (n = 5). No recurrent somatic mutations or copy number alterations were identified in hyalinizing trabecular tumor, whereas RNA-sequencing revealed the presence of a recurrent genetic rearrangement involving PAX8 (2q14.1) and GLIS3 (9p24.2) genes in all cases. In this in-frame fusion gene, which comprised exons 1-2 of PAX8 and exons 3-11 of GLIS3, GLIS3 is likely placed under the regulation of PAX8. Reverse transcription RT-PCR and/or fluorescence in situ hybridization analyses of a validation series of 26 hyalinizing trabecular tumors revealed that the PAX8-GLIS3 gene fusion was present in all hyalinizing trabecular tumors (100%). No GLIS1 rearrangements were identified. Conversely, no PAX8-GLIS3 gene fusions were detected in a cohort of 237 control thyroid neoplasms, including 15 trabecular thyroid lesions highly resembling hyalinizing trabecular tumor from a morphological standpoint, as well as trabecular/solid follicular adenomas, solid/trabecular variants of papillary carcinoma, and Hurthle cell adenomas or carcinomas. Our data provide evidence to suggest that the PAX8-GLIS3 fusion is pathognomonic for hyalinizing trabecular tumors, and that the presence of the PAX8-GLIS3 fusion in thyroid neoplasms may be used as an ancillary marker for the diagnosis of hyalinizing trabecular tumor, thereby avoiding overtreatment in case of misdiagnoses with apparently similar malignant tumors.

Aims: Solid papillary breast carcinoma resembling the tall cell variant of papillary thyroid neoplasms (BPTC), also known as solid papillary carcinoma with reverse polarity, is a rare histological type of breast cancer that resembles morphologically the tall cell variant of papillary thyroid carcinoma. BPTCs are characterised by IDH2 R172 hotspot somatic mutations or mutually exclusive TET2 somatic mutations, concurrently with mutations affecting PI3K pathway-related genes. We sought to characterise their histology and investigate the frequency of IDH2 and PIK3CA mutations in an independent cohort of BPTCs, as well as in conventional solid papillary carcinomas (SPCs)., Methods and Results: Six BPTCs, not previously analysed molecularly, and 10 SPCs were reviewed centrally. Tumour DNA was extracted from microdissected histological sections and subjected to Sanger sequencing of the IDH2 R172 hotspot locus and exons 9 and 20 of PIK3CA. All six BPTCs were characterised by solid, papillary and follicular architecture with circumscribed, invasive tumour nodules composed of epithelial cells with reverse polarity. IDH2 mutations were identified in all six BPTCs (three R172S, two R172T and one R172G), four of which also harboured PIK3CA mutations (two H1047R, one Q546K and one Q546R). By contrast, all SPCs lacked IDH2 mutations, while one of 10 harboured a PIK3CA mutation (H1047R)., Conclusion: We validated the presence of IDH2 R172 hotspot mutations and PIK3CA hotspot mutations in 100% and 67% BPTCs tested, respectively, and documented absence of IDH2 R172 mutations in SPCs. These findings confirm the genotypical-phenotypical correlation reported previously in BPTC, which constitutes an entity distinct from conventional SPC., (© 2018 John Wiley & Sons Ltd.)

Background: Traumatic brain injury (TBI) disproportionately affects lower- and middle-income countries (LMIC). The factors influencing outcomes in LMIC have not been examined as rigorously as in higher-income countries., Methods: This study was conducted to examine clinical and demographic factors influencing TBI outcomes in Latin American LMIC. Data were prospectively collected during a randomized trial of intracranial pressure monitoring in severe TBI and a companion observational study. Participants were aged ≥13 years and admitted to study hospitals with Glasgow Coma Scale score ≤8. The primary outcome was Glasgow Outcome Scale, Extended (GOS-E) score at 6 months. Predictors were analyzed using a multivariable proportional odds model created by forward stepwise selection., Results: A total of 550 patients were identified. Six-month outcomes were available for 88%, of whom 37% had died and 44% had achieved a GOS-E score of 5-8. In multivariable proportional odds modeling, higher Glasgow Coma Scale motor score (odds ratio [OR], 1.41 per point; 95% confidence interval [CI], 1.23-1.61) and epidural hematoma (OR, 1.83; 95% CI, 1.17-2.86) were significant predictors of higher GOS-E score, whereas advanced age (OR, 0.65 per 10 years; 95% CI, 0.57-0.73) and cisternal effacement (P < 0.001) were associated with lower GOS-E score. Study site (P < 0.001) and race (P = 0.004) significantly predicted outcome, outweighing clinical variables such as hypotension and pupillary examination., Conclusions: Mortality from severe TBI is high in Latin American LMIC, although the rate of favorable recovery is similar to that of high-income countries. Demographic factors such as race and study site played an outsized role in predicting outcome; further research is required to understand these associations., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer, has been shown to be driven by MYB pathway activation, most often underpinned by the MYB-NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB-NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB-NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1-ACTN1 and MYBL1-NFIB), which were associated with MYBL1 overexpression. A third AdCC harboured a high-level MYB amplification, which resulted in MYB overexpression at the mRNA and protein levels. RNA-sequencing and whole-genome sequencing revealed no definite alternative driver in the fourth AdCC studied, despite high levels of MYB expression and the activation of pathways similar to those activated in MYB-NFIB-positive AdCCs. In this case, a deletion encompassing the last intron and part of exon 15 of MYB, including the binding site of ERG-1, a transcription factor that may downregulate MYB, and the exon 15 splice site, was detected. In conclusion, we demonstrate that MYBL1 rearrangements and MYB amplification probably constitute alternative genetic drivers of breast AdCCs, functioning through MYBL1 or MYB overexpression. These observations emphasize that breast AdCCs probably constitute a convergent phenotype, whereby activation of MYB and MYBL1 and their downstream targets can be driven by the MYB-NFIB fusion gene, MYBL1 rearrangements, MYB amplification, or other yet to be identified mechanisms. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Aims: Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive hypocellular myxoid stroma, and occur sporadically or in the context of Carney complex, an inheritable condition caused by PRKAR1A-inactivating germline mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12 mutations in the stromal components of the lesions. The aim of this study was to investigate the genomic landscape of MFAs and compare it with that of conventional FAs., Methods and Results: Eleven MFAs from patients without clinical and/or genetic evidence of Carney complex were retrieved. DNA samples of tumour and matching normal tissue were subjected to massively parallel sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay, an assay targeting 410 cancer genes. Genetic alterations detected by MSK-IMPACT were tested in samples in which the stromal and epithelial components were separately laser capture-microdissected. Sequencing revealed no germline PRKAR1A mutations and non-synonymous mutations in six MFAs. Interestingly, in three of the MFAs in which the stromal and epithelial components were separately microdissected, the mutations were found to be restricted to the epithelial rather than the stromal component. The sole exception was a lesion harbouring a somatic truncating PRKAR1A mutation. Upon histological re-review, this case was reclassified as a breast myxoma, consistent with the spectrum of tumous observed in Carney complex patients. In this case, the PRKAR1A somatic mutation was restricted to the stromal component., Conclusion: MFAs lack MED12 mutations, and their stromal components seem not to harbour mutations in the 410 cancer genes tested. Whole-exome and/or whole-genome analyses of MFAs are required to elucidate their genetic drivers., (© 2017 John Wiley & Sons Ltd.)