Clinical practice guidelines for diagnostic and treatment of the chronic heart failure.

Chronic heart failure continues to be one of the main causes of impairment in the functioning and quality of life of people who suffer from it, as well as one of the main causes of mortality in our country and around the world. Mexico has a high prevalence of risk factors for developing heart failure, such as high blood pressure, diabetes, and obesity, which makes it essential to have an evidence-based document that provides recommendations to health professionals involved in the diagnosis and treatment of these patients. This document establishes the clinical practice guide (CPG) prepared at the initiative of the Mexican Society of Cardiology (SMC) in collaboration with the Iberic American Agency for the Development and Evaluation of Health Technologies, with the purpose of establishing recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. This document complies with international quality standards, such as those described by the US Institute of Medicine (IOM), the National Institute of Clinical Excellence (NICE), the Intercollegiate Network for Scottish Guideline Development (SIGN) and the Guidelines International Network (G-I-N). The Guideline Development Group was integrated in a multi-collaborative and interdisciplinary manner with the support of methodologists with experience in systematic literature reviews and the development of CPG. A modified Delphi panel methodology was developed and conducted to achieve an adequate level of consensus in each of the recommendations contained in this CPG. We hope that this document contributes to better clinical decision making and becomes a reference point for clinicians who manage patients with chronic heart failure in all their clinical stages and in this way, we improve the quality of clinical care, improve their quality of life and reducing its complications.

La insuficiencia cardiaca crónica sigue siendo unas de las principales causas de afectación en el funcionamiento y en la calidad de vida de las personas que la presentan, así como una de las primeras causas de mortalidad en nuestro país y en todo el mundo. México tiene una alta prevalencia de factores de riesgo para desarrollar insuficiencia cardiaca, tales como hipertensión arterial, diabetes y obesidad, lo que hace imprescindible contar con un documento basado en la evidencia que brinde recomendaciones a los profesionales de la salud involucrados en el diagnóstico y el tratamiento de estos pacientes. Este documento establece la guía de práctica clínica (GPC) elaborada por iniciativa de la Sociedad Mexicana de Cardiología (SMC) en colaboración con la Agencia Iberoamericana de Desarrollo y Evaluación de Tecnologías en Salud, con la finalidad de establecer recomendaciones basadas en la mejor evidencia disponible y consensuadas por un grupo interdisciplinario y multicolaborativo de expertos. Cumple con estándares internacionales de calidad, como los descritos por el Institute of Medicine de los Estados Unidos de América (IOM), el National Institute of Clinical Excellence (NICE) del Reino Unido, la Intercollegiate Network for Scottish Guideline Development (SIGN) de Escocia y la Guidelines International Network (G-I-N). El grupo de desarrollo de la guía se integró de manera interdisciplinaria con el apoyo de metodólogos con experiencia en revisiones sistemáticas de la literatura y en el desarrollo de GPC. Se llevó a cabo y se condujo metodología de panel Delphi modificado para lograr un nivel de consenso adecuado en cada una de las recomendaciones contenidas en esta GPC. Esperamos que este documento contribuya para la mejor toma de decisiones clínicas y se convierta en un punto de referencia para los clínicos que manejan pacientes con insuficiencia cardiaca crónica en todas sus etapas clínicas, y de esta manera logremos mejorar la calidad en la atención clínica, aumentar la calidad de vida de los pacientes y disminuir las complicaciones de la enfermedad.

Benign Anorectal Disorder Management in Low-Resource Settings.

There are many benign anorectal disorders, which can make patients seek care. In low-resource settings, the incidence of those pathologies is not different from the industrialized and western world. However, an interesting difference colorectal surgeons and gastroenterologists can face is the fact that many patients do not seek help or are not aware and have little opportunities to be helped. Latin America population is estimated to be around 8% of the world population, with Brazil having the largest percentage. Infectious diseases, which were previously under control or were steadily declining, have emerged. For example, we have seen resurgence of dengue, malaria, and syphilis in pregnancy, as well as other sexually transmitted diseases that can affect the anorectal region. In this article, we will address the most common benign anorectal disorders.

A system-wide extracorporeal membrane oxygenation quality collaborative improves patient outcomes.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) use in adult patient populations has grown rapidly with wide variation in practices and outcomes. We evaluated the impact on patient outcomes, resource use, and costs of an initiative to coordinate and standardize best practices across ECMO programs within a large integrated health care system. METHODS: The ECMO Collaborative Project brought clinicians and service-line leaders from 4 programs within a single health care system together with operational subject matter experts tasked with developing and implementing standardized guidelines, order sets, and an internal database to support an automated quarterly report card. Patient outcomes, resource use, and financial measures were compared for the 16 months before (January 2017 to April 2018; "precollaborative," n = 185) versus the 14 months after (November 2018 to December 2019, "postcollaborative," n = 243) a 6-month implementation and blanking period. Subset analyses were performed for venoarterial ECMO, venovenous ECMO, and extracorporeal cardiopulmonary resuscitation. RESULTS: Survival to discharge/transfer increased significantly (in-hospital mortality hazard ratio, 0.75; 95% confidence interval [95% CI], 0.58-0.99) for the postcollaborative versus the precollaborative period (107/185, 57.8% vs 113/243, 46.5%, P = .03), predominantly due to improvement among patients receiving venoarterial ECMO (hazard ratio, 0.61; 95% CI, 0.41-0.91). The percentage of patients successfully weaned from ECMO increased from 58.9% (109/185) to 70% (170/243), P = .02. Complication rates decreased by 40% (incidence rate ratio, 0.60; 95% CI, 0.49-0.72). No significant changes were observed in ECMO duration, intensive care unit or hospital length of stay, or cost-per-case; payment-per-case and contribution-margin-per-case both decreased significantly. CONCLUSIONS: The ECMO Collaborative Project improved survival to discharge/transfer, weaning rates and complications, without additional costs, through coordination and standardization across ECMO programs within a health care system.

Immunogenicity profile in African green monkeys of a vaccine candidate based on a mutated form of human Interleukin-15.

BACKGROUND: Interleukin (IL)-15 is a proinflammatory T-cell growth factor overexpressed in several autoimmune diseases such as rheumatoid arthritis. Our initial strategy to neutralize the increased levels of IL-15 consisted in a vaccine candidate based on the recombinant modified human IL-15 (mhIL-15) mixed with the alum adjuvant. A previous study in non-human primates Macaca fascicularis has shown that vaccination induces neutralizing antibodies against native IL-15, without affecting animal behavior, clinical status, or the percentage of IL-15-dependent cell populations. However, the mhIL-15 used as an antigen was active in the IL-2-dependent cytotoxic T-cell line CTLL-2, which could hinder its therapeutic application. The current article evaluated the immunogenicity in African green monkeys of a vaccine candidate based on IL-15 mutant D8SQ108S, an inactive form of human IL-15. RESULTS: IL-15 D8SQ108S was inactive in the CTLL-2 bioassay but was able to competitively inhibit the biological activity of human IL-15. Immunization with 200 µg of IL-15 mutant combined with alum elicited anti-IL-15 IgG antibodies after the second and third immunizations. The median values of anti-IL-15 antibody titers were slightly higher than those generated in animals immunized with 200 µg of mhIL-15. The highest antibody titers were induced after the third immunization in monkeys vaccinated with 350 µg of IL-15 D8SQ108S. In addition, sera from immunized animals inhibited the biological activity of human IL-15 in CTLL-2 cells. The maximum neutralizing effect was observed after the third immunization in sera of monkeys vaccinated with the highest dose of the IL-15 mutant. These sera also inhibited the proliferative activity of simian IL-15 in the CTLL-2 bioassay and did not affect the IL-2-induced proliferation of the aforementioned T-cell line. Finally, it was observed that vaccination neither affects the animal behavior nor the general clinical parameters of immunized monkeys. CONCLUSION: Immunization with inactive IL-15 D8SQ108S mixed with alum generated neutralizing antibodies specific for human IL-15 in African green monkeys. Based on this fact, the current vaccine candidate could be more effective than the one based on biologically active mhIL-15 for treating autoimmune disorders involving an uncontrolled overproduction of IL-15.

Current Advances in Colorectal Surgery in Latin America: Insights on the 2019 Latin American Association of Coloproctology Congress.

The Latin American Association of Coloproctology (ALACP) held its 26 biennial congress in conjunction with the 44 annual meeting of the Mexican Society of Surgeons of the Rectum, Colon, and Anus (SMCRCA). The meeting took place October 2 to 5, 2019, in Cancun, Mexico. Twenty-eight international professors from North America, Europe, and Asia participated alongside 62 speakers from all of Latin America and the Caribbean. More than 400 participants converged from North, Central, and South America; the Caribbean; Europe; and Asia. Participants included 63 residents from Latin America, Europe, and Asia who contributed an unprecedented number of poster presentations. The meeting was highly interactive, consisting of 1 day of 5 highly dynamic workshops and 3 days of plenary sessions covering a broad spectrum of topics within colorectal surgery. Authoritative lectures by world leaders were punctuated by debates, panel discussions, and presentations of problem cases that delighted the audience. ALACP accomplished transformative changes in its general assembling meetings set into motion by its 26 presidency. These accomplishments included the first reformation of its bylaws in over a quarter century, an official affiliation with Diseases of the Colon & Rectum, and the relocation of the ALACP Secretariat General from Rio de Janeiro to Mexico City.

Advanced heart failure with reduced ejection fraction.

Patients suffering advanced heart failure with reduced ejection fraction (HFrEF) account for a large portion of patients admitted to hospitals worldwide. Mortality and 30-day readmission rates for HFrEF are now a focus of value-based payment models, making management of this disease a priority for hospitals, physicians, and payers alike. Angiotensin-converting enzyme inhibitors have been the cornerstone of therapy for decades. However, with treatment, the prognosis for patients with advanced HFrEF remains poor. Fortunately, advances in medical therapy and mechanical support offer some patients improvement in both survival and quality of life. We review advances in short- and long-term mechanical support and explore changes to organ allocation for cardiac transplantation. In addition, we provide a guide to facilitate appropriate referral to an advanced heart failure team.

Miscellaneous Perianal Afflictions.

This article provides an overview of hidradenitis suppurativa, lichen planus, lichen sclerosis, calcinosis cuti, pyogenic granuloma, intertrigo, and seborrheic keratosis. This article also focuses on recognition and management of these pleomorphic afflictions of the perianal region.

Factors associated with noncomplete mesorectal excision following surgery for rectal adenocarcinoma.

BACKGROUND: The completeness of the resected mesorectum is a quality metric in rectal cancer surgery and has been related to oncological outcomes. Our aim was to identify variables associated with non-complete mesorectal excision and determine any effect on overall survival. METHODS: Consecutive patients who underwent curative intent surgery for rectal adenocarcinoma (2009-2016) were identified from a prospectively-maintained institutional database. Patients were grouped according to their mesorectal grade: complete, near-complete and incomplete. Multivariate analysis was performed to identify the association between various patient, disease and surgeon-related characteristics and mesorectal grading. Log-rank tests were used to evaluate any difference in overall survival between the groups. RESULTS: 689 patients met inclusion criteria. Demographics and perioperative variables were comparable between the groups. On multivariate analysis, abdominoperineal resection, and involved circumferential resection margin were significantly associated with non-complete mesorectum. Finally, patients with non-complete mesorectal grading have approximately twice the hazard of death compared to those with complete mesorectal grading. CONCLUSIONS: Several factors are associated with a non-complete mesorectal excision. Non-complete mesorectal grade is associated with decreased survival.

Role of long-term acute care in reducing hospital readmission.

Long-term acute care hospitals (LTACs) are health care facilities capable of admitting complex patients with high acuity that are unable to return home after hospitalization in acute care. Its defining characteristic is to accommodate patients for a length of stay greater than 25 days, however, little is known about its role of preventing hospital readmissions. Created in the 1980s, these facilities were designed to help acute care facilities improve their resource management, expenditures, and quality of care. Although these units were initially created for chronic ventilator weaning, their scope of practice has broadened. This article analyzes studies and suggests role of LTACs in reducing hospital readmissions.

Screening for immune response against Dengue virus in Vietnamese non-human primates: implications for vaccine developers.

One of the major problems faced for the development of a vaccine against Dengue virus is the lack of a suitable animal model. Although non-human primates do not show overt signs of disease, these animals develop viremia after the infection and are the best model to evaluate vaccine candidates against this pathogen. However, for that purpose, the screening of all animals is mandatory to discard those with previous natural immunity. The most common technique used in the screening is the plaque reduction neutralization test (PRNT). However, most recent studies points to the cell-mediated immunity (CMI) as an important player in the process of controlling Dengue virus (DENV) infections. Here we presented the results from the screening of 55 rhesus monkeys housed in an animal breeding facility at Quang Ninh province, Vietnam. We evaluated the neutralizing antibody response by PRNT and determined the levels of interferon γ (IFNγ)-secretion after the viral stimulation of monkey-peripheral blood mononuclear cells, by enzyme-linked immunosorbent assay (ELISA). We found no correspondence between PRNT and IFNγ-ELISA. In fact, 19 animals were positive only by IFNγ-ELISA. Moreover, to study the protective capacity of the CMI detected, three animals with positive response by IFNγ-ELISA and negative by PRNT were inoculated with an infective preparation of DENV-3 and, as a result, no viremia was detected during 10 days after the challenge. This fact points to the importance of screening non-human primates through a CMI assay together with PRNT. This procedure should discard those false-negative cases which would be protected after the viral challenge in the immunization schedule.

Considering Value in Rectal Cancer Surgery: An Analysis of Costs and Outcomes Based on the Open, Laparoscopic, and Robotic Approach for Proctectomy.

OBJECTIVE: The aim of the study was to compare value (outcomes/costs) of proctectomy in patients with rectal cancer by 3 approaches: open, laparoscopic, and robotic. BACKGROUND: The role of minimally invasive proctectomy in rectal cancer is controversial. In the era of value-based medicine, costs must be considered along with outcomes. METHODS: Primary rectal cancer patients undergoing curative intent proctectomy at our institution between 2010 and 2014 were included. Patients were grouped by approach [open surgery, laparoscopic surgery, and robotic surgery (RS)] on an intent-to-treat basis. Groups were compared by direct costs of hospitalization for the primary resection, 30-day readmissions, and ileostomy closure and for short-term outcomes. RESULTS: A total of 488 patients were evaluated; 327 were men (67%), median age was 59 (27-93) years, and restorative procedures were performed in 333 (68.2%). Groups were similar in demographics, tumor characteristics, and treatment details. Significant outcome differences between groups were found in operative and anesthesia times (longer in the RS group), and in estimated blood loss, intraoperative transfusion, length of stay, and postoperative complications (all higher in the open surgery group). No significant differences were found in short-term oncologic outcomes. Direct cost of the hospitalization for primary resection and total direct cost (including readmission/ileostomy closure hospitalizations) were significantly greater in the RS group. CONCLUSIONS: The laparoscopic and open approaches to proctectomy in patients with rectal cancer provide similar value. If robotic proctectomy is to be widely applied in the future, the costs of the procedure must be reduced.

Active immunization with human interleukin-15 induces neutralizing antibodies in non-human primates.

BACKGROUND: Interleukin-15 is an immunostimulatory cytokine overexpressed in several autoimmune and inflammatory diseases such as Rheumatoid Arthritis, psoriasis and ulcerative colitis; thus, inhibition of IL-15-induced signaling could be clinically beneficial in these disorders. Our approach to neutralize IL-15 consisted in active immunization with structurally modified human IL-15 (mhIL-15) with the aim to induce neutralizing antibodies against native IL-15. In the present study, we characterized the antibody response in Macaca fascicularis, non-human primates that were immunized with a vaccine candidate containing mhIL-15 in Aluminum hydroxide (Alum), Montanide and Incomplete Freund's Adjuvant. RESULTS: Immunization with mhIL-15 elicited a specific antibodies response that neutralized native IL-15-dependent biologic activity in a CTLL-2 cell proliferation assay. The highest neutralizing response was obtained in macaques immunized with mhIL-15 adjuvanted in Alum. This response, which was shown to be transient, also inhibited the activity of simian IL-15 and did not affect the human IL-2-induced proliferation of CTLL-2 cells. Also, in a pool of synovial fluid cells from two Rheumatoid Arthritis patients, the immune sera slightly inhibited TNF-α secretion. Finally, it was observed that this vaccine candidate neither affect animal behavior, clinical status, blood biochemistry nor the percentage of IL-15-dependent cell populations, specifically CD56+ NK and CD8+ T cells. CONCLUSION: Our results indicate that vaccination with mhIL-15 induced neutralizing antibodies to native IL-15 in non-human primates. Based on this fact, we propose that this vaccine candidate could be potentially beneficial for treatment of diseases where IL-15 overexpression is associated with their pathogenesis.

Is there anything we can modify among factors associated with morbidity following elective laparoscopic sigmoidectomy for diverticulitis?

BACKGROUND: Laparoscopic sigmoidectomy for diverticulitis is widely accepted, using either endolinear staplers or traditional linear staplers under direct vision through the extraction site to transect the rectum. The aim of this study was to assess modifiable factors affecting perioperative morbidity after elective laparoscopic sigmoidectomy for diverticulitis. METHODS: Potential associations between perioperative morbidity and demographic, disease-related, and treatment-related factors were assessed on all consecutive patients included in a prospectively collected database undergoing elective laparoscopic sigmoidectomy for diverticulitis between 1992 and 2013. Rectal transection with a linear stapler under direct vision through the extraction site was considered compatible with laparoscopic technique. RESULTS: There were two deaths out of 1059 patients (0.19 %). Conversion rate was 13.1 %, overall morbidity 28 %, and anastomotic leak 3.7 %. Independent factors associated with morbidity in an intent-to-treat analysis were ASA 3 (OR 1.53, p = 0.006), conversion (OR 1.71, p = 0.015), and rectal transection without endolinear stapling (traditional linear stapler: OR 1.75, p = 0.003; surgical knife: OR 2.09, p = 0.002). The same factors along with complicated diverticulitis (OR 1.56, p = 0.013) were independently associated with overall morbidity among laparoscopically completed cases. BMI ≥ 35 (OR 2.3, p = 0.017), complicated diverticulitis (OR 2.37, p = 0.002), and rectal transection with a traditional linear stapler (OR 2.19, p = 0.018) were independently associated with abdomino-pelvic infections, both in an intent-to-treat analysis and among laparoscopically completed cases. The number of endolinear stapler firings was not associated with morbidity. CONCLUSIONS: Most factors associated with morbidity of laparoscopic sigmoidectomy for diverticulitis cannot be easily modified. With the limitation of a retrospective analysis, modifiable factors to minimize morbidity are laparoscopic completion and endolinear stapling.

Medical versus Surgical Patients with Clostridium difficile Infection: Is There Any Difference?

Severity of Clostridium difficile infection (CDI) varies from one patient to another. We aimed to test the hypothesis that surgical patients would suffer more severe CDIs than medical patients. Patients receiving in-hospital medical or surgical treatment for any underlying disease from 2007 to 2012, who developed CDI, were divided into two groups: "Medical group" and "Surgical group." Demographics, disease characteristics, and outcomes including mortality and recurrence were compared. Of 3231 patients with CDI evaluated, 1984 (61.4%) and 1247 (38.6%) were medical and surgical patients, respectively. Surgical patients had more severe CDIs than medical. However, the long-term effects of CDI were worse in medical patients, with more and quicker deaths. Recurrence was comparable between groups. Surgical patients were more frequently male, older, and obese; had higher white blood cells but lower levels of hemoglobin, hematocrit, and prealbumin; and had a higher rate of severe CDI. Conversely, medical patients had fewer in-hospital days, CDI appeared earlier, and had greater 30-day mortality and total number of deaths, with death after CDI occurring earlier. Although surgical patients tend to have a stormier clinical course related to CDI, overall they do better than medical patients. Future studies focusing on modifiable risk factors for each group are needed.

Experimental studies of a vaccine formulation of recombinant human VEGF antigen with aluminum phosphate.

CIGB-247 is a cancer vaccine that is a formulation of a recombinant protein antigen representative of the human vascular endothelial growth factor (VEGF) with a bacterially-derived adjuvant (VSSP). The vaccine has shown an excellent safety profile in mice, rats, rabbits, not-human primates and in recent clinical trials in cancer patients. Response to the vaccine is characterized by specific antibody titers that neutralize VEGF/VEGFR2 binding and a cytotoxic tumor-specific response. To expand our present anti-VEGF active immunotherapy strategies, we have now studied in mice and non-human primates the effects of vaccination with a formulation of our recombinant VEGF antigen and aluminum phosphate adjuvant (hereafter denominated CIGB-247-A). Administered bi-weekly, CIGB-247-A produces high titers of anti-VEGF IgG blocking antibodies in 2 mice strains. Particularly in BALB/c, the treatment impaired subcutaneous F3II mammary tumor growth and reduced the number of spontaneous lung macro metastases, increasing animals' survival. Spleen cells from specifically immunized mice directly killed F3II tumor cells in vitro. CIGB-247-A also showed to be immunogenic in non-human primates, which developed anti-VEGF blocking antibodies and the ability for specific direct cell cytotoxic responses, all without impairing the healing of deep skin wounds or other side effect. Our results support consideration of aluminum phosphate as a suitable adjuvant for the development of new vaccine formulations using VEGF as antigen.

Is it really small-bowel obstruction in patients with paradox after IPAA?

BACKGROUND: Diagnosing outlet obstruction after IPAA can be challenging because the etiology is multifactorial. OBJECTIVE: The aim of this study was to assess possible factors associated with outlet obstruction from paradoxical anal muscle contraction (paradox) after IPAA unrelated to strictures or structural abnormalities. DESIGN: This was a retrospective study from a prospectively maintained pouch database. SETTINGS: The study was conducted at a tertiary referral center. PATIENTS: All of the patients with paradox after ileal J-pouch-anal anastomosis verified by anal physiology were identified from our prospectively maintained database. Patients with endoscopic or digital evidence of strictures or other anatomic abnormalities were excluded. MAIN OUTCOME MEASURES: Demographic, clinical, and perioperative factors were obtained, including previous abdominal operations, history of pouchitis, need for anal intubation, diagnosis of small-bowel obstruction, and radiologic findings at the time of paradox diagnosis. RESULTS: There were 40 patients (17 women) with an overall mean age of 39 years (range, 17-60 years) and a mean follow-up of 15 years (range, 1-28 years) after IPAA. Pathologic diagnoses at the time of ileal pouch creation were ulcerative colitis (n = 27), indeterminate colitis (n = 11), Crohn's disease, and familial adenomatous polyposis (1 case each). A total of 15 (37%) of 40 patients were diagnosed with small-bowel obstruction before their paradox diagnosis, 8 of whom underwent surgery, which revealed diffusely dilated small bowel and pouch without intraoperative identification of a transition point. The time from ileal pouch creation to paradox diagnosis was significantly longer in patients receiving a diagnosis of small-bowel obstruction than in the remaining paradox patients (7.2 vs 2.6 years; p < 0.001). LIMITATIONS: This study was limited by its nonrandomized retrospective nature. CONCLUSIONS: After an IPAA, patients with outlet obstruction from paradox can appear to have a small-bowel obstruction. A high incidence of suspicion is needed to make the correct diagnosis and avoid an unneeded laparotomy.