Manejo y resultados de pacientes con diverticulitis aguda: experiencia de cinco años en el Hospital San Vicente Fundación / Management and results of patients with acute diverticulitis. Five year-experience at the San Vicente Fundación Hospital

Introducción. Los datos epidemiológicos de la diverticulitis en Colombia son limitados. El objetivo de este artículo fue caracterizar una población que ingresó con diverticulitis aguda al Hospital Universitario San Vicente Fundación, un centro de referencia de la ciudad de Medellín, Colombia, para analizar la presentación y comportamiento de la enfermedad en la población local, con estadísticas propias y desenlaces de la enfermedad en los últimos años. Métodos. Estudio observacional retrospectivo, descriptivo, entre enero de 2015 y diciembre de 2019. Se hizo un estudio exploratorio uni-, bi- y multivariado de factores de riesgo para fallo en el tratamiento y la mortalidad. Resultados. Se incluyeron 103 pacientes. Se presentó principalmente en mujeres y la edad promedio fue de 65 años. La diverticulitis Hinchey Ia fue la más frecuente (41,7 %) y el manejo médico fue exitoso en todos los casos, mientras que en las tipo III y IV, todos se manejaron de forma quirúrgica, con tasas de éxito entre el 50 y el 64 %. La presencia de signos de irritación peritoneal al examen físico, el recuento de leucocitos y la PCR, el ingreso a la Unidad de Cuidados Intensivos y la mortalidad aumentaron de forma directamente proporcional con el estadio de Hinchey. Conclusiones. Existe una relación directamente proporcional entre la clasificación de Hinchey y los signos de respuesta inflamatoria clínicos y paraclínicos, la necesidad de manejo quirúrgico, la estancia en la Unidad de Cuidados Intensivos y la mortalidad.

Introduction. Epidemiological data on diverticulitis in Colombia are limited. The objective of this article was to characterize a population that was admitted with acute diverticulitis to the San Vicente Fundación University Hospital, a reference center in the city of Medellín, Colombia, to analyze the presentation and behavior of the disease in the local population, with its own statistics, and outcomes of the disease in recent years. Methods. Retrospective descriptive observational study between January 2015 and December 2019. An exploratory uni-, bi- and multivariate study of risk factors for treatment failure and mortality was performed. Results. A total of 103 patients were included. The most frequent Hinchey classification was Ia (41.7%). It occurs mainly in women, mean age 65 years. Hinchey Ia diverticulitis is the most frequent and medical management is successful in 100% of cases; while in III and IV, 100% were managed surgically with success rates between 50 and 64%. The presence of peritoneal signs on physical examination, leukocyte count and CRP, ICU admission and mortality increased directly proportional with Hinchey stage. Conclusions. There is a directly proportional relationship between Hinchey staging with clinical and paraclinical signs of inflammatory response, need for surgical management, ICU stay and mortality.

Anti-phosphorylcholine IgM, an Anti-inflammatory Mediator, Predicts Peripheral Vein Graft Failure: A Prospective Observational Study.

OBJECTIVES: One third of infrainguinal vein bypasses may fail within the first 1.5 years. Pro- and anti-inflammatory mechanisms are thought to be involved in these graft stenoses and occlusions. In previous studies, low levels of anti-phosphorylcholine IgM (anti-PC IgM, an innate anti-inflammatory IgM) have been associated with increased cardiovascular events. In this study, the peri-operative dynamics of anti-PC IgM levels were established during leg bypass surgery, and associations assessed between anti-PC IgM levels and primary graft patency. DESIGN AND METHODS: This was a prospective, observational cohort study of infrainguinal autogenous vein bypass for peripheral arterial occlusive disease involving four university affiliated hospitals. Plasma cytokine and anti-PC IgM levels were measured pre- and post-operatively. The outcome of interest was loss of primary graft patency because of occlusion or intervention for graft stenosis. RESULTS: One hundred and forty-two consecutive patients were enrolled: mean age 66 (46-91); 91% white race and male; 72.5% critical limb ischaemia (Fontaine III or IV). Median pre-operative anti-PC IgM levels were 49 units/mL (IQR 32.3-107.7, mean 89.8 + 101 sd). During follow up of an average of 1.8 years (1 month-7.4 years), 50 (35.2%) grafts lost primary patency. Pre-operative levels of interleukin 6 or C-reactive protein did not predict graft failure. Patients with pre-operative anti-PC IgM values in the lowest quartile had a twofold increased risk of graft failure (multivariable Cox proportional hazard, p = .03, HR 2.11, 95% CI 1.09-4.07), even after accounting for the other significant factors of conduit diameter, distal anastomosis, smoking, and the severity of leg ischaemia. CONCLUSIONS: Low levels of anti-PC IgM are associated with vein bypass graft failure. This biological mediator may be a useful marker to identify patients at higher risk, and offers the potential for novel, directed therapies for vascular inflammation and its consequences.

Ideación suicida en estudiantes de medicina: prevalencia y factores asociados / Suicide Ideation Among Medical Students: Prevalence and Associated Factors

Introducción: Los médicos tienen mayores tasas de suicidio en comparación con la población general. Este riesgo tiende a incrementarse incluso a partir del inicio de la formación de pregrado en medicina. Existen pocos estudios que evalúen la frecuencia de conductas suicidas en estudiantes de pregrado de medicina, especialmente en Latinoamérica. Objetivo: Determinar la prevalencia de vida y factores asociados con la ideación suicida e intentos suicidas en una muestra de estudiantes de medicina de Bucaramanga, Colombia. Materiales y métodos: Se condujo un estudio observacional analítico de corte transversal, para determinar la prevalencia de vida de ideación suicida e intentos suicidas, en una muestra no probabilística de estudiantes de medicina matriculados en las 3 facultades de medicina de Bucaramanga. El cuestionario autoaplicado fue respondido de forma voluntaria y anónima por los participantes. Las versiones validadas de las escalas CES-D y CAGE fueron utilizadas para evaluar síntomas depresivos y uso problemático de alcohol, respectivamente. Se generó un modelo multivariado de regresión logística, con el fin de ajustar los estimadores de las variables asociadas con el desenlace «ideación suicida alguna vez en la vida¼. Resultados: La muestra de estudio estuvo formada por 963 estudiantes. El 57% (n = 549) de los participantes fueron mujeres. El promedio de edad fue de 20,3 años (DE 2,3 años). En relación con la prevalencia de ideación suicida, el 15,7% (n = 149) de los estudiantes informó haber tenido por lo menos un episodio de ideación suicida serio a lo largo de la vida. El 5% (n = 47) señaló haber realizado por lo menos un intento suicida. El 13,9% (n = 131) de los estudiantes informó haber ingerido antidepresivos durante su entrenamiento médico. Las variables asociadas con la ideación suicida en el modelo de regresión logística fueron: síntomas depresivos clínicamente significativos (OR: 6,9; IC 95%: 4,54-10,4), historia de consumo de sustancias psicoactivas ilícitas (OR: 2,8; IC 95%: 1,6-4,8) y percepción del regular o mal rendimiento académico durante el último año (OR: 2,2; IC 95%: 1,38-3,63). El modelo de regresión logística clasificó correctamente al 85% de los sujetos con antecedente de ideación suicida. Conclusión: La ideación suicida es un fenómeno de frecuente ocurrencia en estudiantes de medicina. Es necesario que las facultades de medicina establezcan programas de detección e intervención temprana que permitan disminuir la probabilidad de ocurrencia de desenlaces negativos.

Introduction: It is well documented that physicians have higher rates of suicide than the general population. This risk tends to increase even from the beginning of undergraduate training in medicine. There are few studies evaluating the frequency of suicidal behaviors in undergraduate medical students, particularly in Latin America. Objective: To determine the lifetime prevalence and the variables associated with suicidal ideation and suicide attempts in a sample of medical students from the city of Bucaramanga, Colombia. Materials and methods: An analytical cross-sectional observational study was conducted to determine the lifetime prevalence of suicidal ideation and suicide attempts in a nonrandom sample of medical students enrolled in three medical schools in Bucaramanga. A self-administered questionnaire was voluntarily and anonymously answered by the participants. Validated versions of the CES-D and CAGE scales were used to assess the presence of depressive symptoms and problematic alcohol use, respectively. A multivariate logistic regression model was generated in order to adjust the estimates of variables associated with the outcome «suicidal ideation in life¼. Results: The study sample consisted of 963 medical students, of which 57% (n = 549) of the participants were women. The average age was 20.3 years (SD = 2.3 years). Having had at least one episode of serious suicidal ideation in their lifetime was reported by 15.7% (n = 149) of the students, with 5% (n = 47) of the students reported having made at least one suicide attempt. Having taken antidepressants during their medical training was reported by 13.9% (n = 131) of the students. The variables associated with the presence of suicidal ideation in the logistic regression model were: clinically significant depressive symptoms (OR: 6.9, 95% CI; 4.54-10.4), history of illicit psychoactive substance use (OR 2.8, 95% CI; 1.6-4.8), and perception of poor academic performance over the past year (OR: 2.2, 95% CI; 1.4-3.6). The logistic regression model correctly classified 85% of the subjects with a history of suicidal ideation. Conclusion: Suicidal ideation is a frequently occurring phenomenon in medical students. Medical schools need to establish screening procedures for early detection and intervention of students with emotional distress and suicide risk.

Low levels of a natural IgM antibody are associated with vein graft stenosis and failure.

BACKGROUND: All humans have natural, protective antibodies directed against phosphorylcholine (PC) epitopes, a common inflammatory danger signal appearing at sites of cell injury, oxidative stress, and on bacterial capsules. In large human cohorts, low levels of anti-PC IgM were associated with a significantly increased risk of stroke or myocardial infarction. However, it is not known if these antibodies protect against the premature closure of arterial reconstructions. METHODS: A prospective, observational study of patients undergoing elective, infrainguinal, autogenous vein bypasses for atherosclerotic occlusive disease of the legs was conducted. Clinical data were recorded prospectively, and preoperative levels of anti-PC IgM measured with the CVDefine kit from Athera Biotechnologies (Solna, Sweden). The principal clinical end point was the loss of primary patency (loss of graft flow, or any intervention for stenosis). Patients were followed regularly by duplex ultrasound at 1, 3, 6, 12, 18 months, and yearly thereafter. RESULTS: Fifty-six patients were studied, for an average of 1.3 years. Indications for surgery were claudication (33.9%), ischemic rest pain (17.9%), and ischemia with ulceration or gangrene (48.2%). Seventeen (30.4%) patients experienced loss of primary patency (10 graft occlusions, seven surgical or endovascular revisions of graft stenoses). Kaplan-Meier survival analysis showed that the quartile of patients with the lowest anti-PC IgM levels had significantly worse primary graft patency (log-rank test, P = .0085). Uni- and multivariate Cox proportional hazards analysis revealed that the preoperative anti-PC IgM level was an important predictor of graft failure. Patients with IgM values in the lowest quartile had a 3.6-fold increased risk of graft failure (95% confidence interval: 1.1-12.1), even after accounting for other significant clinical or technical factors such as indication for surgery, site of distal anastomosis, or vein graft diameter. CONCLUSIONS: A naturally occurring IgM antibody directed against the proinflammatory epitope PC may be protective against vein graft stenosis and failure, through anti-inflammatory mechanisms. Measurement of this antibody may be a useful prognostic indicator, although larger studies of more diverse populations will be needed to confirm these results. The biological actions of anti-PC IgM suggest it may be useful in developing immunotherapies to improve bypass longevity.

Circulating inflammatory cells are associated with vein graft stenosis.

OBJECTIVE: Infrainguinal autogenous vein grafts are especially prone to narrowing and failure, and both inflammatory and thrombotic pathways are implicated. Platelets and monocytes are the key thrombo-inflammatory cells that arrive first at sites of vascular injury. These cells have potent interactions that recruit and activate one another, propagating thrombotic and inflammatory responses within the vessel wall. We therefore hypothesized that elevated levels of platelet-monocyte aggregates (PMA) might be associated with stenosis, and could possibly discriminate between patients with or without vein graft stenosis. METHODS: Thirty-six vascular surgery patients were studied, in a stable quiescent period after infrainguinal autogenous vein graft bypasses for occlusive disease. Eighteen patients had hemodynamically significant graft stenoses confirmed by imaging, and 18 were free from stenosis. The level of PMA in whole blood was quantified after blood draw using two-color flow cytometry. Three measurements were made per sample: the basal, in-vivo level of aggregates (baseline PMA); the predisposition to spontaneously generate PMA (spontaneous PMA); and PMA generation by the addition of exogenous thrombin receptor-activating peptide (stimulated PMA). The baseline, in-vivo level of PMA was estimated by immediate flow analysis. The predisposition to spontaneously generate PMA was measured after in vitro incubation. Responsiveness to thrombin stimulation of the blood was quantified by the in vitro dose response to an exogenous thrombin receptor-activating peptide (sfllrn). RESULTS: Baseline PMA levels were similar in patients with vein graft stenosis vs nonstenosis (14.8% ± 3.2 vs 10.1% ± 1.5, respectively, mean ± SEM). However, patients with stenosis showed higher spontaneous PMA levels (58.5% ± 4.5 vs 28.3% ± 4.3; P < .001) and higher stimulated PMA levels (P < .001; analysis of variance). Covariables of smoking, diabetes, statin, or antithrombotic therapy could not account for these differences. CONCLUSIONS: Platelet-monocyte reactivity may play a role in the development of vein graft stenoses. Those with/without stenosis differed primarily in their threshold, or predisposition to form aggregates (spontaneous PMA), while their basal circulating levels of PMA (baseline PMA) were similar. These measurements may unmask pathologic differences in thrombo-inflammatory responsiveness that are not apparent in basal measurements. Understanding the causes and mechanisms leading to abnormal platelet-monocyte responses may improve approaches to predicting or preventing vein graft stenosis.

Purified viable fat suspended in matrigel improves volume longevity.

BACKGROUND: Autologous fat is an excellent soft tissue filler with cosmetic and reconstructive utility. However, graft longevity is unpredictable. OBJECTIVE: This study sought to evaluate the effect on in vivo fat graft performance of contemporary adipocyte tissue engineering techniques that have not previously been applied to mature fat cells due to the difficulty of their purification and their high metabolic demand. METHODS: Using a recently reported protocol, the adipocyte viability and purity of lipo-harvested fat were optimized. Before graft administration, these purified cells were suspended in GFR-Matrigel (BDBiosciences), a basement membrane protein matrix known to improve early angiogenesis. It was posited that by suspending the purified cells in this resorbable matrix, the high metabolic demand of these cells would be met and graft performance could be improved. The in vivo longevity of these tissue engineered fat grafts was tested in a murine model in which each subject received posterior subcutaneous injections of three types of fat graft: unpurified fat after lipo-harvest alone; fat harvested in identical fashion, but purified and suspended in GFR-Matrigel; and a control of GFR-Matrigel alone. Graft volumes and quantitative histologic characteristics were examined at 1 week, 1 month, and 3 months. RESULTS: At 3 months, purified fat/GFR Matrigel grafts showed superior fat volume maintenance (80.2% versus 29.7% for unpurified grafts [P < .05]) and adipocyte cellular longevity (70.1% versus 45.6% [P < .001). Unpurified grafts were largely replaced by fibrosis at 3 months (96.5% [95% CI 0.90-0.970]), despite starting with three times as many viable adipocytes as purified grafts. A correlation was noted between the poor performance of unpurified grafts and a disproportionate presence of early inflammation in fat grafts prepared without purification techniques. CONCLUSIONS: A preparatory regimen consisting of a preadministration purification followed by cellular suspension in a resorbable protein matrix may ultimately improve the predictability and longevity of autologous fat grafts.

Beyond the cells: scaffold matrix character affects the in vivo performance of purified adipocyte fat grafts.

BACKGROUND: Little attention has been focused on the effect of fat graft structure on in vivo performance. Having hypothesized that a stable initial graft structure was important to fat graft take-similar to the importance of shear minimization in the take of skin grafts-we have previously shown that purified adipocytes suspended in a resorbable protein matrix (GFR Matrigel; BD Biosciences, San Jose, CA) improved in vivo graft longevity. OBJECTIVE: In the present study, the importance of the matrix composition was assessed. METHODS: Age- and sex-matched genetically identical mice were implanted with fat grafts consisting of the same number of purified adult adipocytes mixed with either PuraMatrix (simple peptide hydrogel; 3DM, Cambridge, MA) or GFR Matrigel (basement membrane proteins). Control grafts composed of GFR Matrigel alone, PuraMatrix alone, or syringe-harvested (unpurified) fat alone were also injected. Volume measurements and histologic sections were taken at 1 week, 1 month, and 3 months. RESULTS: Purified fat/GFR Matrigel grafts showed statistically greater longevity and volume maintenance versus all other groups. CONCLUSIONS: Differences in matrix composition in this study were associated with profound changes in graft longevity and volume maintenance. These results suggest that cell-extracellular matrix interactions play an important role in graft survival. Future research into the nature of these interactions may provide an avenue for optimizing fat graft outcomes.

An experimental model for improving fat graft viability and purity.

BACKGROUND: Autologous fat is an excellent soft-tissue filler, given its abundance, ease of harvest, and natural appearance. However, graft longevity is unpredictable and is reported in the literature to be between 3 months and 8 years. METHODS: A genetically identical, age- and sex-matched mouse experiment was used to develop a model. Inguinal fat pads were subjected to different harvest and preparatory techniques. Primary endpoints-viability and purity-were assessed with the trypan blue viability assay and component counting with a hemocytometer. RESULTS: Viability and purity were highest after excisional harvest versus blunt or needle harvest, presumably secondary to differences in cellular trauma. Saline wash or centrifugation after harvest produced modest but statistically significant improvements in viability and purity. However, if grafts harvested in any fashion were treated with an initial collagenase digestion followed by an idealized centrifugation regimen and a single wash step, viability and purity were consistently 96 percent and 93 percent, respectively. CONCLUSIONS: Using an in vitro murine model, the authors have systematically developed a clinically practical model for creating a pure single-cell suspension of viable adipocytes that is reproducible, regardless of tissue harvest method.