Reducing the global burden of cerebral venous thrombosis: An international research agenda.

BACKGROUND: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized. AIMS: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding. SUMMARY OF REVIEW: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion. CONCLUSIONS: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide.

Predictors of Mortality in Patients with Infections Due to Carbapenem-Resistant Gram-Negative Bacteria.

INTRODUCTION: Infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) are a significant cause of mortality and represent a serious challenge to health systems. The early identification of mortality predictors could guide appropriate treatment and follow-up. We aimed to identify the factors associated with 90-day all-cause mortality in patients with CR-GNB infections. METHODS: We conducted a cohort study from 1 January 2019 to 30 April 2022. The primary outcome was death from any cause during the first 90 days after the date of the first CR-GNB-positive culture. Secondary outcomes included infection relapse, invasive mechanical ventilation during follow-up, need for additional source control, acute kidney injury, Clostridioides difficile infection, and all-cause hospital admission after initial discharge. Bivariate and multivariate Cox-proportional hazards models were constructed to identify the factors independently associated with 90-day all-cause mortality. RESULTS: A total of 225 patients with CR-GNB infections were included. Death occurred in 76 (34%) cases. The most-reported comorbidities were immunosuppression (43%), arterial hypertension (35%), and COVID-19 (25%). The median length of stay in survivors was 18 days (IQR 10-34). Mechanical ventilation and ICU admission after diagnosis occurred in 8% and 11% of cases, respectively. Both infection relapse and rehospitalisation occurred in 18% of cases. C. difficile infection was diagnosed in 4% of cases. Acute kidney injury was documented in 22% of patients. Mechanical ventilation after diagnosis, ICU admission after diagnosis, and acute kidney injury in the first ten days of appropriate treatment were more frequently reported among non-survivors. In the multivariate analysis, age (HR 1.19 (95%CI 1.00-1.83)), immunosuppression (HR 1.84 (95%CI 1.06-3.18)), and septic shock at diagnosis (HR 2.40 (95% 1.41-4.08)) had an independent association with death during the first 90 days after the CR-GNB infection diagnosis. Receiving antibiogram-guided appropriate treatment was independently associated with a lower risk of death (HR 0.25 (95%CI 0.14-0.46)). CONCLUSIONS: The presence of advanced age, immunosuppression, septic shock at diagnosis, and inappropriate treatment are associated with higher 90-day all-cause mortality in hospitalised patients with infections due to CR-GNB. Recognition of the risk factors for adverse outcomes could further assist in patient care and the design of interventional studies that address the severe and widespread problem that is carbapenem resistance.

Endoscopic ultrasound-guided drainage of a pelvic abscess - An alternative use of lumen-apposing metallic stents.

The use of lumen-apposing metal stent is well defined for endoscopic ultrasound-guided drainage of pancreatic collections (e.g. WON). However, it is not yet a well-established approach in the management of postsurgical collections. We present an alternative application of LAMS for EUS drainage of pelvic abscess, showing that it is a safe and minimally invasive technique, with excellent clinical results. This technique should be considered as a drainage alternative in these scenarios due to its lower morbidity and mortality, opening a new era in the approach to these lesions.

Biallelic mismatch repair deficiency – A rare and troublesome genetic syndrome

Biallelic mismatch repair deficiency (BMMRD) is a rare autosomal recessive disorder characterized by numerous early-onset cancers, especially gastrointestinal tumors. Biallelic germline mutations in one of four mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) cause this devastating disease. Given the rarity of the syndrome, often-asymptomatic tumors, diagnosis is frequently unrecognized or delayed. A high degree of clinical awareness is needed to identify new cases. Immunohistochemical assessment of MMR protein expression and analysis of microsatellite instability are the first tools with which to initiate the study of this syndrome in solid malignancies. MMR immunohistochemical shows a hallmark pattern with absence of staining in both neoplastic and non-neoplastic cells for the biallelic mutated gene. We present a unique case of a young boy diagnosed with invasive colon adenocarcinoma and brain tumor, with classical BMMRD features, found to have biallelic pathogenic PMS2 mutations. (AU)

Preventing Obesity in Midlife Women: A Recommendation From the Women's Preventive Services Initiative.

DESCRIPTION: The Women's Preventive Services Initiative (WPSI), a national coalition of women's health professional organizations and patient advocacy representatives, developed a recommendation for counseling midlife women aged 40 to 60 years with normal or overweight body mass index (BMI; 18.5 to 29.9 kg/m2) to maintain weight or limit weight gain to prevent obesity with the long-term goals of optimizing health, function, and well-being. This recommendation is intended to guide clinical practice and coverage of clinical preventive health services for the Health Resources and Services Administration and other stakeholders. Clinicians providing preventive health care to women in primary care settings are the target audience for this recommendation. METHODS: The WPSI developed this recommendation after evaluating results of a systematic review of the effectiveness and harms of interventions to prevent weight gain and obesity in women aged 40 to 60 years without obesity. Seven randomized clinical trials including 51 638 participants and using various counseling and behavioral interventions were included. Trials indicated favorable weight changes with interventions that were statistically significantly different from control groups in 4 of 5 trials of counseling, but not in 2 trials of exercise. Few harms were reported. RECOMMENDATION: The WPSI recommends counseling midlife women aged 40 to 60 years with normal or overweight BMI (18.5 to 29.9 kg/m2) to maintain weight or limit weight gain to prevent obesity. Counseling may include individualized discussion of healthy eating and physical activity.

Deconstructing Difflugia: The tangled evolution of lobose testate amoebae shells (Amoebozoa: Arcellinida) illustrates the importance of convergent evolution in protist phylogeny.

Protists, the micro-eukaryotes that are neither plants, animals nor fungi build up the greatest part of eukaryotic diversity on Earth. Yet, their evolutionary histories and patterns are still mostly ignored, and their complexity overlooked. Protists are often assumed to keep stable morphologies for long periods of time (morphological stasis). In this work, we test this paradigm taking Arcellinida testate amoebae as a model. We build a taxon-rich phylogeny based on two mitochondrial (COI and NADH) and one nuclear (SSU) gene, and reconstruct morphological evolution among clades. In addition, we prove the existence of mitochondrial mRNA editing for the COI gene. The trees show a lack of conservatism of shell outlines within the main clades, as well as a widespread occurrence of morphological convergences between far-related taxa. Our results refute, therefore, a widespread morphological stasis, which may be an artefact resulting from low taxon coverage. As a corollary, we also revise the groups systematics, notably by emending the large and highly polyphyletic genus Difflugia. These results lead, amongst others, to the erection of a new infraorder Cylindrothecina, as well as two new genera Cylindrifflugia and Golemanskia.

Biallelic mismatch repair deficiency - A rare and troublesome genetic syndrome.

Biallelic mismatch repair deficiency (BMMRD) is a rare autosomal recessive disorder characterized by numerous early-onset cancers, especially gastrointestinal tumors. Biallelic germline mutations in one of four mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) cause this devastating disease. Given the rarity of the syndrome, often-asymptomatic tumors, diagnosis is frequently unrecognized or delayed. A high degree of clinical awareness is needed to identify new cases. Immunohistochemical assessment of MMR protein expression and analysis of microsatellite instability are the first tools with which to initiate the study of this syndrome in solid malignancies. MMR immunohistochemical shows a hallmark pattern with absence of staining in both neoplastic and non-neoplastic cells for the biallelic mutated gene. We present a unique case of a young boy diagnosed with invasive colon adenocarcinoma and brain tumor, with classical BMMRD features, found to have biallelic pathogenic PMS2 mutations.

Growing Healthy Together: A Randomized Clinical Trial Using Parent Mentors for Early Childhood Obesity in Low-Income, Latino Families.

Background: Parent mentors are a potential community-based mechanism for delivering behavioral interventions. For communities at a higher risk of obesity and challenges with access to care, such as migrant and seasonal farm workers, this may be an effective intervention for obesity. This study examined the effect of parent mentors on weight outcomes. Methods: This randomized clinical trial assigned parents of 2- to 5 year-old children enrolled in Head Start 1:1:1 to control, a parent mentor teaching We Can!, or a parent mentor teaching an intervention derived from positive deviance methods. The parent mentor arms were designed to have weekly interactions and monthly community meetings over 6 months. The primary outcome was change in adiposity, as measured by body mass indices. Results: We randomized 188 parents, and 155 completed the 6-month visit. Most parents, 107 (58%), had less than a high school education, and 170 (90%) reported Latino ethnicity. In the intention-to-treat analysis, no difference between the groups was observed for change in percent distance from the median or BMI z-score. The median number of interactions was 14 (IQR 10-20) over 6 months for those who did engage, though 24 of 118 (20%) had no interaction. Those with no interactions in We Can! had a mean increase in change from median of 6.7 [standard deviation (SD) = 8.2]; those with higher participation experienced a 0.4 (SD = 9.2) change, p = 0.04. Conclusions: Parent mentors were not effective in changing the adiposity indices in this study overall, with some evidence of efficacy after accounting for participation. Clinicaltrials.gov registration number: NCT03330743.

Cuidados de enfermería para reducir infecciones por microorganismos oportunistas en pacientes oncológicos / Nursing care to reduce infections by opportunistic microorganisms in oncology patients

Introducción: las infecciones generadas por microorganismos oportunistas (MO) o infecciones oportunistas (IO) son causa importante de morbimortalidad en pacientes oncológicos y se les atribuyen factores relacionados con los cuidados específicos de la atención en salud. Las alteraciones en el sistema inmunológico, la multirresistencia antimicrobiana, la neutropenia febril y la interrupción de la integridad cutánea son los factores más influyentes. Objetivo: describir las principales intervenciones y estrategias para reducir IO en pacientes oncológicos. Metodología: revisión integrativa de la literatura. Se incluyeron artículos en español, inglés y portugués indexados a los tesauros MeSH Y DeCS, en las bases de datos CINAHL, Nursing Ovid, Clinicalkey; el metabuscador de Google académico y la interfaz Pubmed. Resultados: se revisaron 56 estudios, fueron organizados en tres temáticas: factores de riesgo que influyen para adquirir una IO en pacientes oncológicos, infecciones por MO y cuidados de enfermería, los cuales se agruparon en subtemas como: educación, medidas estándar, de barrera, farmacológicas, nutrición, manejo de catéteres, cavidad bucal, piel y aspectos emocionales. Discusión: se evidencian factoresque influyen en la no adherencia por parte de los profesionales que están relacionados con sus posturas, el contexto social, el sistema sanitario y características de las GPC. Conclusión: fue posible describir las intervenciones y estrategias de prevención que permiten reducir de manera importante la morbimortalidad en pacientes oncológicos.

Introduction: infections caused by opportunistic microorganisms (OM) or opportunistic infections (OI) are an important source of morbidity and mortality in oncology patients and are attributed to factors related with specific procedures in health care. Alterations of the immune system, antimicrobial multidrug resistance, febrile neutropenia and impaired skin integrity are the most influential factors. Objective: to describe the main interventions and strategies to reduce OI in oncology patients. Methodology: integrative review of the literature. Articles in Spanish, English and Portuguese indexed in the MeSH and DeCS thesauri in the CINAHL, Nursing Ovid, Clinicalkey databases; the academic Google meta-search engine and the PubMed interface, were included. Results: 56 studies were reviewed and organized into three topics: risk factors associated with the development of OI in cancer patients, infections by OM and nursing care. These topics were grouped into subtopics such as: education, standard barrier and pharmacological measures, nutrition, IV catheter care, oral cavity, skin and emotional aspects. Discussion: factors influencing non-adherence of healthcare providers were found to be related with their attitude, social context, health system and characteristics of clinical practice guidelines. Conclusion: we describe the intervention and prevention strategies which allow a significant reduction in morbimortality in oncology patients.

Cuidar en tiempos de pandemia: experiencia de una auxiliar de enfermería en Bogotá / Caring in times of pandemic: experience of a nursing assistant in Bogotá

Introducción: La atención en salud en tiempos de pandemia ha requerido un gran compromiso de los integrantes de los equipos de atención en salud, quienes se han visto afectados por los múltiples cambios. Objetivo: Describir la experiencia de cuidar durante la pandemia por Covid-19 de una auxiliar de enfermería en Bogotá. Metodología: Estudio cualitativo, relato biográfico, se realizó entrevista a una auxiliar de enfermería de primera línea en la atención, y análisis temático de la información. Resultados: El tema central permite aproximarse al proceso de transitar por el cambio, del cual se desarrollan cinco subtemas que visibilizan la vulnerabilidad de la participante ante esta situación y la urgente necesidad de atención. Conclusión: Cuidar en primera línea en tiempos de pandemia ha tenido múltiples implicaciones que trascienden el quehacer profesional y se reflejan en la vida personal, familiar y social. (AU)

Background: Health care in times of pandemic has required a great commitment of the members of health care teams, who have been affected by the many changes. Objective: To describe the experience of caring for a nursing assistant in Bogotá during the Covid-19 pandemic. Methods: Qualitative study, biographical account, an interview was conducted at a nursing assistant frontline care, and thematic analysis of information. Results: The central theme allows to approach the process of going through change, of which five sub-themes are developed that make visible the vulnerability of the participant in this situation and the urgent need for attention. Conclusions: Frontline care in times of pandemic has had many implications that go beyond the professional work and are reflected in the personal, family and social life. (AU)

Consideraciones sobre el síndrome de hipermovilidad articular benigna / Considerations for benign joint hypermobility syndrome

El síndrome de hipermovilidad articular benigna es la aparición de síntomas musculoesqueléticos en individuos hipermóviles en ausencia de enfermedad reumatológica sistémica. El propósito de este estudio es mostrar los resultados de una revisión bibliográfica sobre hipermovilidad de las articulaciones y sus manifestaciones clínicas. La hipermovilidad puede ocurrir en varios trastornos diferentes del tejido conectivo, incluidos el síndrome de Marfán, el síndrome de Ehlers-Danlos y la osteogénesis imperfecta. También se puede encontrar en ciertos trastornos cromosómicos, genéticos y metabólicos. Identificar de manera habitual la hipermovilidad articular, y el síndrome de hipermovilidad articular no resulta una tarea difícil, siempre que forme parte del pensamiento clínico, lo cual ayudaría a evitar sus complicaciones y las tardanzas diagnósticas, lo que solucionaría en una medida nada despreciable los casos que se atienden regularmente en la práctica médica diaria(AU)

ABSTRACT Benign joint hypermobility syndrome is the appearance of musculoskeletal symptoms in hypermobile individuals in the absence of systemic rheumatologically disease. To show the results of a bibliographic review on joint hypermobility and its clinical manifestations. Hypermobility can occur in several different connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfect. It can also be found in certain chromosomal, genetic, and metabolic disorders. Identifying joint hypermobility on a regular basis, and JHS is not a difficult task, as long as it is part of clinical thinking, which would help to avoid its complications and diagnostic delays, which would solve a not inconsiderable measure of cases that they are regularly cared for in daily medical practice.

AddTag, a two-step approach with supporting software package that facilitates CRISPR/Cas-mediated precision genome editing.

CRISPR/Cas-induced genome editing is a powerful tool for genetic engineering, however, targeting constraints limit which loci are editable with this method. Since the length of a DNA sequence impacts the likelihood it overlaps a unique target site, precision editing of small genomic features with CRISPR/Cas remains an obstacle. We introduce a two-step genome editing strategy that virtually eliminates CRISPR/Cas targeting constraints and facilitates precision genome editing of elements as short as a single base-pair at virtually any locus in any organism that supports CRISPR/Cas-induced genome editing. Our two-step approach first replaces the locus of interest with an "AddTag" sequence, which is subsequently replaced with any engineered sequence, and thus circumvents the need for direct overlap with a unique CRISPR/Cas target site. In this study, we demonstrate the feasibility of our approach by editing transcription factor binding sites within Candida albicans that could not be targeted directly using the traditional gene-editing approach. We also demonstrate the utility of the AddTag approach for combinatorial genome editing and gene complementation analysis, and we present a software package that automates the design of AddTag editing.

Microbiome and oral squamous cell carcinoma: a possible interplay on iron metabolism and its impact on tumor microenvironment.

There is increasing evidence showing positive association between changes in oral microbiome and the occurrence of oral squamous cell carcinoma (OSCC). Alcohol- and nicotine-related products can induce microbial changes but are still unknown if these changes are related to cancerous lesion sites. In an attempt to understand how these changes can influence the OSCC development and maintenance, the aim of this study was to investigate the oral microbiome linked with OSCC as well as to identify functional signatures and associate them with healthy or precancerous and cancerous sites. Our group used data of oral microbiomes available in public repositories. The analysis included data of oral microbiomes from electronic cigarette users, alcohol consumers, and precancerous and OSCC samples. An R-based pipeline was used for taxonomic and functional prediction analysis. The Streptococcus spp. genus was the main class identified in the healthy group. Haemophilus spp. predominated in precancerous lesions. OSCC samples revealed a higher relative abundance compared with the other groups, represented by an increased proportion of Fusobacterium spp., Prevotella spp., Haemophilus spp., and Campylobacter spp. Venn diagram analysis showed 52 genera exclusive of OSCC samples. Both precancerous and OSCC samples seemed to present a specific associated functional pattern. They were menaquinone-dependent protoporphyrinogen oxidase pattern enhanced in the former and both 3',5'-cyclic-nucleotide phosphodiesterase (purine metabolism) and iron(III) transport system ATP-binding protein enhanced in the latter. We conclude that although precancerous and OSCC samples present some differences on microbial profile, both microbiomes act as "iron chelators-like" potentially contributing to tumor growth.

Screening for Anxiety in Adolescent and Adult Women: A Recommendation From the Women's Preventive Services Initiative.

DESCRIPTION: The Women's Preventive Services Initiative (WPSI), a national coalition of women's health professional organizations and patient representatives, developed a recommendation on screening for anxiety in adolescent and adult women to improve detection; achieve earlier diagnosis and treatment; and improve health, function, and well-being. The WPSI's recommendations are intended to guide clinical practice and coverage of services for the Health Resources and Services Administration and other stakeholders. The target audience for this recommendation includes all clinicians providing preventive health care to women, particularly in primary care settings. This recommendation applies to women and adolescent girls aged 13 years or older who are not currently diagnosed with anxiety disorders, including pregnant and postpartum women. METHODS: The WPSI developed this recommendation after evaluating results of a systematic review of the effectiveness of screening, accuracy of screening instruments, and benefits and harms of treatments in adolescent girls and adult women. No studies directly evaluated the overall effectiveness or harms of screening for anxiety. Twenty-seven screening instruments and their variations were moderately to highly accurate in identifying anxiety (33 individual studies and 2 systematic reviews; 171 studies total). Symptoms improved and relapse rates decreased with psychological therapies (246 randomized controlled trials [RCTs] in 5 systematic reviews) and with selective serotonin reuptake inhibitors or selective serotonin and norepinephrine reuptake inhibitors (126 RCTs in 3 systematic reviews). The WPSI also considered the effect of screening on symptom progression and identification of associated and underlying conditions, as well as implementation factors. RECOMMENDATION: The WPSI recommends screening for anxiety in women and adolescent girls aged 13 years or older who are not currently diagnosed with anxiety disorders, including pregnant and postpartum women. Optimal screening intervals are unknown, and clinical judgment should be used to determine frequency. When screening suggests the presence of anxiety, further evaluation is necessary to establish the diagnosis and determine appropriate treatment and follow-up.

A Prematurity Collaborative Birth Equity Consensus Statement for Mothers and Babies.

INTRODUCTION: In 2016, March of Dimes (MOD) launched its Prematurity Collaborative to engage a broad cross section of national experts to address persistent and widening racial disparities in preterm birth by achieving equity and demonstrated improvements in preterm birth. African-American and Native American women continue to have disproportionate rates of preterm birth and maternal death. As part of the Collaborative, MOD created the Health Equity Workgroup whose task was the creation of a scientific consensus statement articulating core values and a call to action to achieve equity in preterm birth utilizing health equity and social determinants of health frameworks. METHODS: Health Equity Workgroup members engaged in-person and virtually to discuss key determinant contributors and resolutions for disparate maternal and birth outcomes. Workgroup members then drafted the Birth Equity Consensus Statement that contained value statements and a call to action. The birth equity consensus statement was presented at professional conferences to seek broader support. This article highlights the background and context towards arriving at the core values and call to action, which are the two major components of the consensus statement and presents the core values and call to action themselves. RESULTS: The result was the creation of a birth equity consensus statement that highlights risks and protections of social determinants based on the prevailing science, and identifies promising solutions for reducing preterm birth and eliminating racial disparities. CONCLUSION: The birth equity consensus statement provides a mandate, guiding the work of March of Dimes and the broader MCH community, for equity-based research, practice, and policy advocacy at local, state, and federal levels. SIGNIFICANCE: This field report adds to the current knowledge base on racial and ethnic disparities in birth and maternal health outcomes. Research has documented the science behind eliminating health disparities. Scientists and practitioners should continue to explore in practice how the social determinants of birth and maternal health, which manifest historically and contemporarily, can be addressed.