Evaluation and Management of Biliary Dyskinesia in Children and Adolescents: A Systematic Review From the APSA Outcomes and Evidence-Based Committee.

INTRODUCTION: The diagnosis and management of biliary dyskinesia in children and adolescents remains variable and controversial. The American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee (APSA OEBP) performed a systematic review of the literature to develop evidence-based recommendations. METHODS: Through an iterative process, the membership of the APSA OEBP developed five a priori questions focused on diagnostic criteria, indications for cholecystectomy, short and long-term outcomes, predictors of success/benefit, and outcomes of medical management. A systematic review was conducted, and articles were selected for review following Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. Risk of bias was assessed using Methodologic Index for Non-Randomized Studies (MINORS) criteria. The Oxford Levels of Evidence and Grades of Recommendation were utilized. RESULTS: The diagnostic criteria for biliary dyskinesia in children and adolescents are not clearly defined. Cholecystectomy may provide long-term partial or complete relief in some patients; however, there are no reliable predictors of symptom relief. Some patients may experience resolution of symptoms with non-operative management. CONCLUSIONS: Pediatric biliary dyskinesia remains an ill-defined clinical entity. Pediatric-specific guidelines are necessary to better characterize the condition, guide work-up, and provide management recommendations. Prospective studies are necessary to more reliably identify patients who may benefit from cholecystectomy. LEVEL OF EVIDENCE: Level 3-4. TYPE OF STUDY: Systematic Review of Level 3-4 Studies.

Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities.

An important host defence mechanism against pathogens is intracellular killing, which is achieved through phagocytosis, a cellular process for engulfing and neutralizing extracellular particles. Phagocytosis results in the formation of matured phagolysosomes, which are specialized compartments that provide a hostile environment and are considered the end point of the degradative pathway. However, all fungal pathogens studied to date have developed strategies to manipulate phagosomal function directly and also indirectly by redirecting phagosomes from the degradative pathway to a non-degradative pathway with the expulsion and even transfer of pathogens between cells. Here, using the major human fungal pathogens Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Histoplasma capsulatum as examples, we discuss the processes involved in host phagosome-fungal pathogen interactions, with a focus on fungal evasion strategies. We also discuss recent approaches to targeting intraphagosomal pathogens, including the redirection of phagosomes towards degradative pathways for fungal pathogen eradication.

Screening and Prophylaxis for Venous Thromboembolism in Pediatric Surgery: A Systematic Review.

OBJECTIVE: The American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee conducted a systematic review to describe the epidemiology of venous thromboembolism (VTE) in pediatric surgical and trauma patients and develop recommendations for screening and prophylaxis. METHODS: The Medline (Ovid), Embase, Cochrane, and Web of Science databases were queried from January 2000 through December 2021. Search terms addressed the following topics: incidence, ultrasound screening, and mechanical and pharmacologic prophylaxis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. Consensus recommendations were derived based on the best available literature. RESULTS: One hundred twenty-four studies were included. The incidence of VTE in pediatric surgical populations is 0.29% (Range = 0.1%-0.48%) and directly correlates with surgery type, transfusion, prolonged anesthesia, malignancy, congenital heart disease, inflammatory bowel disease, infection, and female sex. The incidence of VTE in pediatric trauma populations is 0.25% (Range = 0.1%-0.8%) and directly correlates with injury severity, major surgery, central line placement, body mass index, spinal cord injury, and length-of-stay. Routine ultrasound screening for VTE is not recommended. Consider sequential compression devices in at-risk nonmobile, pediatric surgical patients when an appropriate sized device is available. Consider mechanical prophylaxis alone or with pharmacologic prophylaxis in adolescents >15 y and post-pubertal children <15 y with injury severity scores >25. When utilizing pharmacologic prophylaxis, low molecular weight heparin is superior to unfractionated heparin. CONCLUSIONS: While VTE remains an infrequent complication in children, consideration of mechanical and pharmacologic prophylaxis is appropriate in certain populations. TYPE OF STUDY: Systematic Review of level 2-4 studies. LEVEL OF EVIDENCE: Level 3-4.

Management and Outcomes of Pediatric Lymphatic Malformations: A Systematic Review From the APSA Outcomes and Evidence-Based Practice Committee.

BACKGROUND: Significant variation in management strategies for lymphatic malformations (LMs) in children persists. The goal of this systematic review is to summarize outcomes for medical therapy, sclerotherapy, and surgery, and to provide evidence-based recommendations regarding the treatment. METHODS: Three questions regarding LM management were generated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Publicly available databases were queried to identify articles published from January 1, 1990, to December 31, 2021. A consensus statement of recommendations was generated in response to each question. RESULTS: The initial search identified 9326 abstracts, each reviewed by two authors. A total of 600 abstracts met selection criteria for full manuscript review with 202 subsequently utilized for extraction of data. Medical therapy, such as sirolimus, can be used as an adjunct with percutaneous treatments or surgery, or for extensive LM. Sclerotherapy can achieve partial or complete response in over 90% of patients and is most effective for macrocystic lesions. Depending on the size, extent, and location of the malformation, surgery can be considered. CONCLUSION: Evidence supporting best practices for the safety and effectiveness of management for LMs is currently of moderate quality. Many patients benefit from multi-modal treatment determined by the extent and type of LM. A multidisciplinary approach is recommended to determine the optimal individualized treatment for each patient.

Mammary adipocytes promote breast tumor cell invasion and angiogenesis in the context of menopause and obesity.

The mechanism(s) underlying obesity-related postmenopausal (PM) breast cancer (BC) are not clearly understood. We hypothesized that the increased local presence of 'obese' mammary adipocytes within the BC microenvironment promotes the acquisition of an invasive and angiogenic BC cell phenotype and accelerates tumor proliferation and progression. BC cells, treated with primary mammary adipocyte secretome from premenopausal (Pre-M) and PM obese women (ObAdCM; obese adipocyte conditioned-media) upregulated the expression of several pro-tumorigenic factors including VEGF, lipocalin-2 and IL-6. Both Pre-M and PM ObAdCM stimulated endothelial cell recruitment and proliferation and significantly stimulated BC cell proliferation, migration and invasion. IL-6 and LCN2 induced STAT3/Akt signaling in BC cells and STAT3 inhibition abrogated the ObAdCM-stimulated BC cell proliferation and migration. Expression of proangiogenic regulators including VEGF, NRP1, NRP2, IL8RB, TGFß2, and TSP-1 were found to be differentially regulated in mammary adipocytes from obese PM women. Comparative RNAseq indicated an upregulation of PI3K/Akt signaling, ECM-receptor interactions and lipid/fatty acid metabolism in PM versus Pre-M mammary adipocytes. Our results demonstrate that irrespective of menopausal status, cross-talk between obese mammary adipocytes and BC cells promotes tumor aggressiveness and suggest that targeting the LCN2/IL-6/STAT3 signaling axis may be a useful strategy in obesity-driven breast tumorigenesis.

Management of Gastroschisis: Timing of Delivery, Antibiotic Usage, and Closure Considerations (A Systematic Review From the American Pediatric Surgical Association Outcomes & Evidence Based Practice Committee).

BACKGROUND: No consensus exists for the initial management of infants with gastroschisis. METHODS: The American Pediatric Surgical Association (APSA) Outcomes and Evidenced-based Practice Committee (OEBPC) developed three a priori questions about gastroschisis for a qualitative systematic review. We reviewed English-language publications between January 1, 1970, and December 31, 2019. This project describes the findings of a systematic review of the three questions regarding: 1) optimal delivery timing, 2) antibiotic use, and 3) closure considerations. RESULTS: 1339 articles were screened for eligibility; 92 manuscripts were selected and reviewed. The included studies had a Level of Evidence that ranged from 2 to 4 and recommendation Grades B-D. Twenty-eight addressed optimal timing of delivery, 5 pertained to antibiotic use, and 59 discussed closure considerations (Figure 1). Delivery after 37 weeks post-conceptual age is considered optimal. Prophylactic antibiotics covering skin flora are adequate to reduce infection risk until definitive closure. Studies support primary fascial repair, without staged silo reduction, when abdominal domain and hemodynamics permit. A sutureless repair is safe, effective, and does not delay feeding or extend length of stay. Sedation and intubation are not routinely required for a sutureless closure. CONCLUSIONS: Despite the large number of studies addressing the above-mentioned facets of gastroschisis management, the data quality is poor. A wide variation in gastroschisis management was documented, indicating a need for high quality RCTs to provide an evidence-based approach when caring for these infants. TYPE OF STUDY: Qualitative systematic review of Level 1-4 studies.

Outpatient cervical ripening and labor induction with low-dose vaginal misoprostol reduces the interval to delivery: a systematic review and network meta-analysis.

OBJECTIVE: Several systematic reviews and meta-analyses have summarized the evidence on the efficacy and safety of various outpatient cervical ripening methods. However, the method with the highest efficacy and safety profile has not been determined conclusively. We performed a systematic review and network meta-analysis of published randomized controlled trials to assess the efficacy and safety of cervical ripening methods currently employed in the outpatient setting. DATA SOURCES: With the assistance of an experienced medical librarian, we performed a systematic search of the literature using MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. We systematically searched electronic databases from inception to January 14, 2020. STUDY ELIGIBILITY CRITERIA: We considered randomized controlled trials comparing a variety of methods for outpatient cervical ripening. METHODS: We conducted a frequentist random effects network meta-analysis employing data from randomized controlled trials. We performed a direct, pairwise meta-analysis to compare the efficacy of various outpatient cervical ripening methods, including placebo. We employed ranking strategies to determine the most efficacious method using the surface under the cumulative ranking curve; a higher surface under the cumulative ranking curve value implied a more efficacious method. We assessed the following outcomes: time from intervention to delivery, cesarean delivery rates, changes in the Bishop score, need for additional ripening methods, incidence of Apgar scores <7 at 5 minutes, and uterine hyperstimulation. RESULTS: We included data from 42 randomized controlled trials including 6093 participants. When assessing the efficacy of all methods, 25 µg vaginal misoprostol was the most efficacious in reducing the time from intervention to delivery (surface under the cumulative ranking curve of 1.0) without increasing the odds of cesarean delivery, the need for additional ripening methods, the incidence of a low Apgar score, or uterine hyperstimulation. Acupressure (surface under the cumulative ranking curve of 0.3) and primrose oil (surface under the cumulative ranking curve of 0.2) were the least effective methods in reducing the time to delivery interval. Among effective methods, 50 mg oral mifepristone was associated with the lowest odds of cesarean delivery (surface under the cumulative ranking curve of 0.9). CONCLUSION: When balancing efficacy and safety, vaginal misoprostol 25 µg represents the best method for outpatient cervical ripening.

Insights into exercise-induced rhinitis based on nasal aerodynamics induced by airway morphology.

BACKGROUND: Exercise-induced rhinitis (EIR) is a poorly understood phenomenon that may be related to increased inspiratory airflow. Characterization of the development of EIR is important to understand contributing factors. OBJECTIVE: To characterize how different nasal morphologies respond to airflow-related variables during rapid/deep inspiratory conditions. METHODS: Subject-specific nasal airways were reconstructed from radiographic images. Unilateral airways were classified as Standard, Notched, or Elongated accord to their distinct nasal vestibule morphology. Computational fluid dynamics simulations were performed at various airflow rates. RESULTS: For all simulated flow rates, average resistance at the nasal vestibule, airflow velocity and wall sheer stress were highest in Notched. Average mucosal heat flux was highest in Standard. Notched phenotypes showed lower mean percent increases from 10 L/min to 50 L/min in all computed variables. CONCLUSION: Resistance values and airflow velocities depicted a more constricted nasal vestibule in the Notched phenotypes, while perception of nasal mucosal cooling (heat flux) favored the Standard phenotypes. Different nasal phenotypes may predispose to EIR.

Factors that impact initiation of pain management agreements for patients on chronic opioid therapy.

OBJECTIVE: This analysis seeks to understand variables within our institution that impact pain management agreement (PMA) utilization for chronic noncancer pain (CNCP). DESIGN: Retrospective chart review. SETTING: Public academic medical center. PATIENTS: Adults prescribed an opioid for CNCP between July 2020 and October 2020. MAIN OUTCOME MEASURE: We assessed the association between patient demographics, prescription factors, and prescriber factors with the presence of a PMA. Unadjusted rates and chi-square tests were generated for each predictor. Additionally, we performed two multivariable logistic regressions: one including all variables and another utilizing a stepwise forward variable selection process to further understand the relationships between predictors and the presence of a PMA. RESULTS: 49.7 percent of patients who received an opioid for CNCP had a PMA on file. One significant predictor of the presence of PMA was prescriber specialty with anesthesia/pain medicine, demonstrating 88 percent compliance. Compared to anesthesia/pain medicine, patients receiving opioids from internal medicine had an odds ratio (OR) of 0.155 (95 percent confidence interval (CI), 0.109-0.220), while patients receiving opioids from family medicine had an OR of 0.122 (95 percent CI, 0.090-0.167). Additionally, patients who received schedule II opioids (as opposed to schedule III/IV opioids), patients with multiple opioid fills in 3 months, middle aged patients, and Black patients were more likely to have a PMA. CONCLUSIONS: Compliance with PMA within our institution was only 49 percent despite an existing state law mandating use. Our analysis suggests quality improvement interventions should target patients on schedule III/IV opioids who receive their prescriptions from primary care providers.

Evaluation and Management of Primary Spontaneous Pneumothorax in Adolescents and Young Adults: A Systematic Review From the APSA Outcomes & Evidence-Based Practice Committee.

INTRODUCTION: Controversy exists in the optimal management of adolescent and young adult primary spontaneous pneumothorax. The American Pediatric Surgical Association (APSA) Outcomes and Evidence-Based Practice Committee performed a systematic review of the literature to develop evidence-based recommendations. METHODS: Ovid MEDLINE, Elsevier Embase, EBSCOhost CINAHL, Elsevier Scopus, and Wiley Cochrane Central Register of Controlled Trials databases were queried for literature related to spontaneous pneumothorax between January 1, 1990, and December 31, 2020, addressing (1) initial management, (2) advanced imaging, (3) timing of surgery, (4) operative technique, (5) management of contralateral side, and (6) management of recurrence. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Seventy-nine manuscripts were included. Initial management of adolescent and young adult primary spontaneous pneumothorax should be guided by symptoms and can include observation, aspiration, or tube thoracostomy. There is no evidence of benefit for cross-sectional imaging. Patients with ongoing air leak may benefit from early operative intervention within 24-48 h. A video-assisted thoracoscopic surgery (VATS) approach with stapled blebectomy and pleural procedure should be considered. There is no evidence to support prophylactic management of the contralateral side. Recurrence after VATS can be treated with repeat VATS with intensification of pleural treatment. CONCLUSIONS: The management of adolescent and young adult primary spontaneous pneumothorax is varied. Best practices exist to optimize some aspects of care. Further prospective studies are needed to better determine optimal timing of operative intervention, the most effective operation, and management of recurrence after observation, tube thoracostomy, or operative intervention. LEVEL OF EVIDENCE: Level 4. TYPE OF STUDY: Systematic Review of Level 1-4 studies.

Sweet syndrome and erythema nodosum in a young patient with ulcerative colitis.

Sweet syndrome (SS) or acute febrile neutrophilic dermatosis is a rare inflammatory skin condition presenting as an abrupt onset of painful erythematous plaques or nodules, fever, and neutrophilia with histopathology showing a dense neutrophilic infiltrate. Systemic corticosteroids are the gold standard treatment for SS. We describe a case of a 26-year-old with a past medical history of ulcerative colitis on chronic prednisone presenting to the hospital with a 3-week ulcerative colitis flare with concomitant erythema nodosum and SS. While SS is well described, this inflammatory skin condition is uncommon in the setting of chronic anti-inflammatory medication.

Surgical Management of Ulcerative Colitis in Children and Adolescents: A Systematic Review from the APSA Outcomes and Evidence-Based Practice Committee.

INTRODUCTION: The incidence of ulcerative colitis (UC) is increasing. Roughly 20% of all patients with UC are diagnosed in childhood, and children typically present with more severe disease. Approximately 40% will undergo total colectomy within ten years of diagnosis. The objective of this study is to assess the available evidence regarding the surgical management of pediatric UC as determined by the consensus agreement of the American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee (APSA OEBP). METHODS: Through an iterative process, the membership of the APSA OEBP developed five a priori questions focused on surgical decision-making for children with UC. Questions focused on surgical timing, reconstruction, use of minimally invasive techniques, need for diversion, and risks to fertility and sexual function. A systematic review was conducted, and articles were selected for review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of Bias was assessed using Methodological Index for Non-Randomized Studies (MINORS) criteria. The Oxford Levels of Evidence and Grades of Recommendation were utilized. RESULTS: A total of 69 studies were included for analysis. Most manuscripts contain level 3 or 4 evidence from single-center retrospective reports, leading to a grade D recommendation. MINORS assessment revealed a high risk of bias in most studies. J-pouch reconstruction may result in fewer daily stools than straight ileoanal anastomosis. There are no differences in complications based on the type of reconstruction. The timing of surgery should be individualized to patients and does not affect complications. Immunosuppressants do not appear to increase surgical site infection rates. Laparoscopic approaches result in longer operative times but shorter lengths of stay and fewer small bowel obstructions. Overall, complications are not different using an open or minimally invasive approach. CONCLUSIONS: There is currently low-level evidence related to certain aspects of surgical management for UC, including timing, reconstruction type, use of minimally invasive techniques, need for diversion, and risks to fertility and sexual function. Multicenter, prospective studies are recommended to better answer these questions and ensure the best evidence-based care for our patients. LEVEL OF EVIDENCE: Level of evidence III. STUDY TYPE: Systematic review.

Polymer-based particles against pathogenic fungi: A non-uptake delivery of compounds.

The therapy of life-threatening fungal infections is limited and needs urgent improvement. This is in part due to toxic side effects of clinically used antifungal compounds or their limited delivery to fungal structures. Until today, it is a matter of debate how drugs or drug-delivery systems can efficiently reach the intracellular lumen of fungal cells and how this can be improved. Here, we addressed both questions by applying two different polymeric particles for delivery of compounds. Their formulation was based on two biocompatible polymers, i.e., poly(lactic-co-glycolic acid)50:50 and poly(methyl methacrylate-stat-methacrylic acid)90:10 yielding particles with hydrodynamic diameters ranging from 100 to 300 nm. The polymers were covalently labeled with the fluorescent dye DY-550 to monitor the interaction between particles and fungi by confocal laser scanning microscopy. Furthermore, the fluorescent dye coumarin-6 and the antifungal drug itraconazole were successfully encapsulated in particles to study the fate of both the cargo and the particle when interacting with the clinically most important human-pathogenic fungi Aspergillus fumigatus, A. terreus, Candida albicans, and Cryptococcus neoformans. While the polymers were exclusively located on the fungal surface, the encapsulated cargo was efficiently transported into fungal hyphae, indicated by increased intracellular fluorescence signals due to coumarin-6. In accordance with this finding, compared to the pristine drug a reduced minimal inhibitory concentration for itraconazole was determined, when it was encapsulated. Together, the herein used polymeric particles were not internalized by pathogenic fungi but were able to efficiently deliver hydrophobic cargos into fungal cells.

Targeting of phagolysosomes containing conidia of the fungus Aspergillus fumigatus with polymeric particles.

Conidia of the airborne human-pathogenic fungus Aspergillus fumigatus are inhaled by humans. In the lung, they are phagocytosed by alveolar macrophages and intracellularly processed. In macrophages, however, conidia can interfere with the maturation of phagolysosomes to avoid their elimination. To investigate whether polymeric particles (PPs) can reach this intracellular pathogen in macrophages, we formulated dye-labeled PPs with a size allowing for their phagocytosis. PPs were efficiently taken up by RAW 264.7 macrophages and were found in phagolysosomes. When macrophages were infected with conidia prior to the addition of PPs, we found that they co-localized in the same phagolysosomes. Mechanistically, the fusion of phagolysosomes containing PPs with phagolysosomes containing conidia was observed. Increasing concentrations of PPs increased fusion events, resulting in 14% of phagolysosomes containing both conidia and PPs. We demonstrate that PPs can reach conidia-containing phagolysosomes, making these particles a promising carrier system for antimicrobial drugs to target intracellular pathogens. KEY POINTS: • Polymer particles of a size larger than 500 nm are internalized by macrophages and localized in phagolysosomes. • These particles can be delivered to Aspergillus fumigatus conidia-containing phagolysosomes of macrophages. • Enhanced phagolysosome fusion by the use of vacuolin1 can increase particle delivery.

Use of a Modified ABTHERA ADVANCE™ Open Abdomen Dressing with Intrathoracic Negative-Pressure Therapy for Temporary Chest Closure After Damage Control Thoracotomy.

BACKGROUND Damage control surgery (DCS) is an established emergency operative concept, initially described and most often utilized in abdominal trauma. DCS prioritizes managing acute hemorrhage and contamination, leaving the abdominal wall fascia open and covering the existing wound with a temporary abdominal wall closure, most commonly negative-pressure wound therapy (NPWT). The patient undergoes aggressive resuscitation to optimize physiology. Once achieved, the patient is returned to the operating room for definitive surgical intervention. There is limited evidence suggesting that using damage control thoracotomy within the chest cavity improves mortality and morbidity rates. Our review failed to find a case in which NPWT using ABTHERA ADVANCE™ Open Abdomen Dressing has been successfully used in the setting of thoracic trauma. CASE REPORT This case series describes 2 examples of NPWT as a form of temporary chest closure in penetrating and blunt thoracic injury. The first case was a penetrating self-inflicted stab wound to the chest. The NPWT was applied as a form of temporary thoracotomy, closure at the index surgery. The second case was a blunt injury to the chest of a polytrauma patient following a motor vehicle accident. The patient sustained rib fractures on his left side and had a bilateral pneumothorax. An emergent thoracotomy was performed due to delayed intrathoracic bleeding noted on hospital day 11, and NPWT was applied as described above, in the first case. CONCLUSIONS These cases suggest that damage control thoracotomy with intrathoracic placement of a modified ABTHERA ADVANCE™ Open Abdomen Dressing negative-pressure system may be an effective and life-saving technique with the potential for positive outcomes in these high-risk patients.

The Impact of the Rate of Weight Loss on Body Composition and Metabolism.

PURPOSE OF REVIEW: Weight loss has multiple beneficial effects on body composition and metabolism, but whether these depend on the rate at which body weight is lost is not clear. We analyzed data from studies in which the same amount of weight loss was induced rapidly or gradually. RECENT FINDINGS: Thirteen studies were included in which the same percentage weight loss was achieved at slow or fast rates (range: 0.2 to 3.2 kg/week) by means of dietary calorie restriction, exercise, and bariatric surgery. Faster rates of weight loss may result in more fat-free mass and less fat mass being lost during the dynamic phase of weight reduction compared with slower rates of weight loss, in conjunction with greater declines in resting energy expenditure. However, these differences are attenuated after 2-4 weeks of stabilization at the new, lower body weight, and do not affect the rate and amount of weight regain 9-33 months later (nor the tissue composition of regained weight). Differences in waist circumference, visceral and liver fat contents, resting blood pressure, fasting blood lipid profile, and insulin and adipokine concentrations in response to different rates of weight loss are trivial. The decline in fasting glucose concentration and the improvement in insulin sensitivity after 6-11% weight loss are both greater with rapid than gradual weight loss, but not different after 18-20% weight loss. Changes in body composition and metabolism after losing the same amount of body weight at different rates are largely similar, and occasional differences are likely not meaningful clinically for the long-term management of obesity and cardiometabolic diseases.

Mitochondrial Genetic Diversity, Population Structure and Detection of Antillean and Amazonian Manatees in Colombia: New Areas and New Techniques.

The Antillean manatee (Trichechus manatus) and the Amazonian manatee (Trichechus inunguis) are distributed in rivers in the Caribbean and Amazonian region of Colombia respectively. For 30 years, genetic information has been obtained from these populations in order to inform conservation programs for these endangered species and decide on the location to release them back to the wild. However, in previous studies, samples from rivers in some areas of the country were not included, given the difficulties to access these regions due to either logistic or safety issues. In this study, we analyzed mitochondrial DNA (mtDNA) control region (CR) sequences of from samples of T. manatus (n = 37) and T. inunguis (n = 4) (410 and 361 bp, respectively), obtained in new and previously unexplored rivers and bays in the country, including Santa Marta, Urabá Gulf, Ayapel Marsh (San Jorge River Basin), Meta River and Magdalena Medio and the low Magdalena River (Cesar Province and Canal del Dique) as well as additional samples from Puerto Nariño in the Colombian Amazon. Our results included the discovery of two newly described mtDNA CR haplotypes for T. manatus. In addition, we confirmed significant population differentiation at the mitochondrial level between the Magdalena and Sinú rivers and differentiation among areas of the same river, including the middle and low Magdalena River. This differentiation may be related to anthropic changes in the river since construction of the Canal del Dique in the XVI century. We also tested environmental DNA sampling and analyses techniques to evaluate its potential use for manatee detection and monitoring in bodies of water in Colombia, in order to evaluate new areas for future manatee conservation initiatives. We emphasize the need to continue using genetic information to provide evidence on the potential best locations to undertake animal release to prevent outbreeding depression.

Resumen ejecutivo: Enfermedad por hígado graso no alcohólico en sujetos con diabetes mellitus tipo 2: Postura conjunta de la Asociación Chilena de Hepatología (ACHHEP) y la Sociedad Chilena de Diabetología (SOCHIDIAB) / Non-alcoholic fatty liver disease in type 2 diabetes: a joint statement of the Chilean Hepatology and Diabetology Societies

Non-alcoholic fatty liver disease (NAFLD) has a high prevalence and risk of progression to cirrhosis and other complications in patients with type 2 diabetes mellitus (T2DM). Likewise, the presence of NAFLD implies a high risk of developing T2DM, determining a bidirectional relationship between them. The diabetology and hepatology societies, developed a joint initiative aiming to unify criteria, reviewing the definitions, diagnostic criteria, risk stratification, treatment, and follow-up of patients with NAFLD and T2DM. The key questions to be discussed were defined by a panel of specialists in diabetology and hepatology. The Delphi methodology was used to reach consensus on the respective recommendations. Based on the discussion generated among the experts, diagnostic and treatment algorithms were proposed, as well as an indication for referral and the role of the different specialists involved in the management of these patients. Strengthening multidisciplinary work with patients with NAFLD and T2DM will allow the early recognition of the disease, the prevention of the progression to cirrhosis, and reducing the associated complications.

Frecuencia de conductas autolesivas y factores asociados en adolescentes escolarizados de Manizales Colombia / Frequency of self-injurious behaviors and associated factors in school adolescents from Manizales, Colombia

Objetivo: esta investigación pretende determinar la frecuencia de conductas autolesivas en una muestra de estudiantes de un colegio de Manizales (Caldas, Colombia). En las últimas dos décadas las conductas autolesivas han aumentado significativamente en la población adolescente. Materiales y métodos: se empleó una muestra por conveniencia de 58 estudiantes (de una población de 538). Se cuantificaron variables demográficas, la frecuencia de conductas autolesivas, factores de riesgo, y se cuantificaron mediante escalas la satisfacción familiar, ansiedad y depresión y acoso escolar (bullying). Resultados: se encontró que una proporción de 22,4% presentaban conductas autolesivas (auto corte, auto golpearse, auto arañarse, intoxicación, arrancarse el cabello, auto quemarse), 10,3% consumo de sustancias psicoactivas, 36,4% consumo de bebidas alcohólicas, 50% probable ansiedad, 56,9% probable depresión. 66,95% de satisfacción familiar. Como factores asociados a autolesiones se encontraron ansiedad, depresión, orientación sexual, consumo de sustancias psicoactivas, bebidas alcohólicas e intento de suicidio en los últimos dos años. Conclusiones: la prevalencia de conductas autolesivas y los factores asociados a estas conductas en esta población es similar a lo reportado en el país y en el mundo, situación que llama la atención, más si se tiene en cuenta que es un importante predictor de suicidio; por tanto, es urgente que las autoridades competentes de la ciudad desarrollen e implementes intervenciones educativas dirigidas a reducir los factores de riesgo de CA, y así, contribuir a la disminución potencial de las tasas de suicidio en Manizales..(Au)

Objective: this research aims to determine the frequency of self-injurious behaviors in a sample of students from a school in Manizales (Caldas, Colombia). In the last two decades, self-injurious behaviors have increased significantly in the adolescent population. Materials and methods: a convenience sample of 58 students (from a population of 538) was used. Demographic variables, the frequency of self-injurious behavior, risk factors were quantified, and family satisfaction, anxiety and depression, and bullying were quantified using scales. Results: it was found that a proportion of 22.4% had self-injurious behaviors (self-cutting, self-hitting, self-scratching, intoxication, hair pulling, self-burning), 10.3% consumption of psychoactive substances, 36.4% consumption of alcoholic beverages, 50% probable anxiety, 56.9% probable depression. 66.95 family satisfaction. As factors associated with self-harm, anxiety, depression, sexual orientation, consumption of psychoactive substances, alcoholic beverages and attempted suicide in the last two year were found. Conclusions: a frequency of self-harm was determined in this population, and associated factors similar to that found in other student populations nationally and internationally. It was determined that this phenomenon of global importance is also present, to a considerable extent, in young students from Manizales city (Colombia)..(Au)