Combined Robotic Ventral Mesh Rectopexy and Sacrocolpopexy for Multicompartmental Pelvic Organ Prolapse.

BACKGROUND: Multispecialty management should be the preferred approach for the treatment of pelvic floor dysfunction because there is often multicompartmental prolapse. OBJECTIVE: To assess the safety of combined robotic ventral mesh rectopexy and either uterine or vaginal fixation for the treatment of multicompartmental pelvic organ prolapse at our institution. DESIGN: Retrospective analysis. SETTINGS: Tertiary referral academic center. PATIENTS: All patients who underwent a robotic approach and combined procedure and whose cases were discussed at a biweekly pelvic floor multidisciplinary team meeting. MAIN OUTCOME MEASURES: Operative time, intraoperative blood loss and complications, postoperative pelvic organ prolapse quantification score, length of stay, 30-day morbidity, and readmission. RESULTS: From 2018 to 2021, there were 321 operations for patients with multicompartmental prolapse. The mean age was 63.4 years. The predominant pelvic floor dysfunction was rectal prolapse in 170 cases (60%). Pelvic organ prolapse quantification scores were II in 146 patients (53%), III in 121 patients (44%), and IV in 9 patients (3%); 315 of 323 cases included robotic ventral mesh rectopexy (98%). Sacrocolpopexy or sacrohysteropexy was performed in 281 patients (89%). Other procedures included 175 hysterectomies (54%), 104 oophorectomies (32%), 151 sling procedures (47%), 149 posterior repairs (46%), and 138 cystocele repairs (43%). The operative time for ventral mesh rectopexy was 211 minutes and for combined pelvic floor reconstruction was 266 minutes. Average length of stay was 1.6 days. Eight patients were readmitted within 30 days: 1 with a severe headache and 7 with postoperative complications (2.5%), such as pelvic collection and perirectal collection, both requiring radiologic drainage. Four complications required reoperation: epidural abscess, small-bowel obstruction, missed enterotomy requiring resection, and urinary retention requiring sling revision. There were no mortalities. LIMITATIONS: Retrospective single-center study. CONCLUSIONS: A combined robotic approach for multicompartmental pelvic organ prolapse is a safe and viable procedure with a relatively low rate of morbidity and no mortality. This is the highest volume series of combined robotic pelvic floor reconstruction in the literature and demonstrates a low complication rate and short length of stay. See Video Abstract . RECTOPEXIA Y SACROCOLPOPEXIA ROBTICA VENTRAL COMBINADAS CON MALLA PARA EL PROLAPSO DE RGANOS PLVICOS MULTICOMPARTIMENTALES: ANTECEDENTES:El tratamiento multiespecializado debe ser el enfoque preferido para el tratamiento de la disfunción del suelo pélvico, ya que a menudo hay prolapso multicompartimental.OBJETIVO:Evaluar la seguridad de la rectopexia robótica combinada con malla ventral y fijación uterina o vaginal para el tratamiento del prolapso multicompartimental de órganos pélvicos en nuestra institución.DISEÑO:Análisis retrospectivo.AJUSTES:Centro académico de referencia terciarioPACIENTES:Todos los pacientes que se sometieron a un enfoque robótico y un procedimiento combinado y se discutieron en una reunión quincenal del equipo multidisciplinario sobre el piso pélvico.MEDIDAS DE RESULTADO:Tiempo operatorio, pérdida de sangre intraoperatoria y complicaciones. Puntuación de cuantificación del prolapso de órganos pélvicos posoperatorio, duración de la estancia hospitalaria, morbilidad a 30 días y reingreso.RESULTADOS:De 2018 a 2021, se realizaron 321 operaciones de pacientes con prolapso multicompartimental. La edad media fue 63.4 años. La disfunción del suelo pélvico predominante fue el prolapso rectal en 170 casos (60%). Las puntuaciones de cuantificación del prolapso de órganos pélvicos fueron II en 146 pacientes (53%), III en 121 (44%) y IV en 9 (3%); 315 de los 323 casos incluyeron rectopexia robótica de malla ventral (98%). Se realizó sacrocolpopexia o sacrohisteropexia en 281 pacientes (89%). Otros procedimientos incluyeron 175 histerectomías (54%), 104 ooforectomías (32%), 151 procedimientos de cabestrillo (47%), 149 reparaciones posteriores (46%) y 138 reparaciones de cistocele (43%). El tiempo operatorio para la rectopexia con malla ventral fue de 211 minutos y la reconstrucción combinada del piso pélvico de 266 minutos. La estancia media fue de 1.6 días. Ocho pacientes reingresaron dentro de los 30 días, 1 con dolor de cabeza intenso y 7 pacientes con complicaciones posoperatorias (2.5%): colección pélvica y colección perirrectal, ambas requirieron drenaje radiológico. Cuatro complicaciones requirieron reoperación: absceso epidural, obstrucción del intestino delgado, enterotomía omitida que requirió resección y retención urinaria que requirió revisión del cabestrillo. No hubo mortalidades.LIMITACIONES:Estudio retrospectivo unicéntrico.CONCLUSIONES:Un enfoque robótico combinado para el prolapso multicompartimental de órganos pélvicos es un procedimiento seguro y viable con una tasa relativamente baja de morbilidad y ninguna mortalidad. Esta es la serie de mayor volumen de reconstrucción robótica combinada del suelo pélvico en la literatura y demuestra una baja tasa de complicaciones y una estancia hospitalaria corta. (Traducción-Dr. Aurian Garcia Gonzalez )See Editorial on page 195.

Comparing three-dimensional endorectal ultrasound and magnification chromoendoscopy for early rectal neoplasia invasion depth assessment.

INTRODUCTION: Accurate assessment of invasion depth of early rectal neoplasms is essential for optimal therapy. We aimed to compare three-dimensional endorectal ultrasound (3D-ERUS) with magnification chromoendoscopy (MCE) regarding their accuracy in assessing parietal invasion depth (T). METHODS: Patients with middle and distal rectum neoplasms were prospectively included. Two providers blinded to each other's assessment performed 3D-ERUS and MCE, respectively. The T stage assessed through ERUS was compared to the MCE evaluation. The results were compared to the surgical specimen anatomopathological report. Sensitivity, specificity, accuracy, positive (PPV), and negative (NPV) predictive values were calculated for the T stage and for the final therapy (local excision or radical surgery). RESULTS: In 8 years, 70 patients were enrolled, and all underwent both exams. MCE and ERUS showed an accuracy of 94.3% and 85.7%, sensitivity of 83.7 and 93.3%, specificity of 96.4 and 83.6%, PPV of 86.7 and 60.9%, and NPV of 96.4 and 97.9%, respectively. Kappa for T stage assessed through ERUS was 0.64 and 0.83 for MCE. CONCLUSION: MCE and 3D-ERUS had good diagnostic performance, but the endoscopic method had higher accuracy. Both methods reliably assessed lesion extension, circumferential involvement, and distance from the anal verge.

Intramolecular Cyclization of Azido-Isocyanides Triggered by the Azide Anion: An Experimental and Computational Study.

This work describes the unprecedented intramolecular cyclization occurring in a set of α-azido-ω-isocyanides in the presence of catalytic amounts of sodium azide. These species yield the tricyclic cyanamides [1,2,3]triazolo[1,5-a]quinoxaline-5(4H)-carbonitriles, whereas in the presence of an excess of the same reagent, the azido-isocyanides convert into the respective C-substituted tetrazoles through a [3 + 2] cycloaddition between the cyano group of the intermediate cyanamides and the azide anion. The formation of tricyclic cyanamides has been examined by experimental and computational means. The computational study discloses the intermediacy of a long-lived N-cyanoamide anion, detected by NMR monitoring of the experiments, subsequently converting into the final cyanamide in the rate-determining step. The chemical behavior of these azido-isocyanides endowed with an aryl-triazolyl linker has been compared with that of a structurally identical azido-cyanide isomer, experiencing a conventional intramolecular [3 + 2] cycloaddition between its azido and cyanide functionalities. The synthetic procedures described herein constitute metal-free approaches to novel complex heterocyclic systems, such as [1,2,3]triazolo[1,5-a]quinoxalines and 9H-benzo[f]tetrazolo[1,5-d][1,2,3]triazolo[1,5-a][1,4]diazepines.

Ischemia-guided vs routine non-culprit vessel angioplasty for patients with ST segment elevation myocardial infarction and multi-vessel disease: the IAEA SPECT STEMI trial.

BACKGROUND: In patients with multi-vessel disease presenting with ST elevation myocardial infarction (STEMI), the efficacy and safety of ischemia-guided, vs routine non-culprit vessel angioplasty has not been adequately studied. METHODS: We conducted an international, randomized, non-inferiority trial comparing ischemia-guided non-culprit vessel angioplasty to routine non-culprit vessel angioplasty, following primary PCI for STEMI. The primary outcome was the between-group difference in percent ischemic myocardium at follow-up stress MPI. All MPI images were processed and analyzed at a central core lab, blinded to treatment allocation. RESULTS: In all, 109 patients were enrolled from nine countries. In the ischemia-guided arm, 25/48 (47%) patients underwent non-culprit vessel PCI following stress MPI. In the routine non-culprit PCI arm, 43/56 (77%) patients underwent angioplasty (86% within 6 weeks of randomization). The median percentage of ischemic myocardium on follow-up imaging (mean 16.5 months) was low, and identical (2.9%) in both arms (difference 0.13%, 95%CI - 1.3%-1.6%, P < .0001; non-inferiority margin 5%). CONCLUSION: A strategy of ischemia-guided non-culprit PCI resulted in low ischemia burden, and was non-inferior to a strategy of routine non-culprit vessel PCI in reducing ischemia burden. Selective non-culprit PCI following STEMI offers the potential for cost-savings, and may be particularly relevant to low-resource settings. (CTRI/2018/08/015384).

"That's why we're speaking up today": exploring barriers to overdose fatality prevention in Indianapolis' Black community with semi-structured interviews.

BACKGROUND: Opioid overdose deaths are of great concern to public health, with over one million lives lost since 1999. While many efforts have been made to mitigate these, Black communities continue to experience a greater burden of fatalities than their white counterparts. This study aims to explore why by working with Black community members in Indianapolis through semi-structured interviews. METHODS: Semi-structured one-on-one in-depth interviews were conducted in spring and summer of 2023 with Black residents (N = 23) of zip codes 46202, 46205, 46208, and 46218 in Indianapolis. Ten interview questions were used to facilitate conversations about opioid overdoses, recovery, fatality prevention tools such as calling 911 and naloxone, law enforcement, and racism. Data were analyzed using grounded theory and thematic analysis. RESULTS: Interviews revealed access barriers and intervention opportunities. Racism was present in both. Mental access barriers such as stigma, fear, and mistrust contributed to practical barriers such as knowledge of how to administer naloxone. Racism exacerbated mental barriers by adding the risk of race-based mistreatment to consequences related to association with substance use. Participants discussed the double stigma of substance use and being Black, fear of being searched in law enforcement encounters and what would happen if law enforcement found naloxone on them, and mistrust of law enforcement and institutions that provide medical intervention. Participants had favorable views of interventions that incorporated mutual aid and discussed ideas for future interventions that included this framework. CONCLUSIONS: Racism exacerbates Blacks' mental access barriers (i.e., help-seeking barriers), which, in turn, contribute to practical barriers, such as calling 911 and administering naloxone. Information and resources coming from people within marginalized communities tend to be trusted. Leveraging inter-community relationships may increase engagement in opioid overdose fatality prevention. Interventions and resources directed toward addressing opioid overdose fatalities in Black communities should use mutual aid frameworks to increase the utilization of the tools they provide.

The double-barrel wet colostomy: An alternative for urinary diversion after pelvic exenteration.

AIM: Pelvic exenteration is a radical procedure used to treat locally advanced and/or recurrent pelvic malignancies. Different reconstruction options exist, the most popular being the end colostomy with ileal conduit. The double barrel wet colostomy (DBWC) offers concomitant fecal and urinary diversion through a single stoma, but is infrequently utilized. We aim to review the evidence base of the postoperative complications, long-term oncologic risks and quality of life following creation of a double barrel wet colostomy. METHODS: A narrative review of the literature was performed evaluating the DBWC. Patient demographics, perioperative complications, operative variables, long terms oncologic outcomes and quality of life data were extracted. Descriptive statistics were used to define the data. RESULTS: Fourteen articles with a total of 300 patients undergoing DBWC following pelvic exenteration were selected. 41% of malignancies were gastrointestinal in origin while 41.7% were gynecologic and 5.3% genitourinary. 42% of patients experienced at least one complication within in 40 days of surgery, the most common being wound infection (8.7%) and urinary leak (8.3%). There was no evidence of malignancy within the DBWC during long-term surveillance. Quality of life following DBWC is comparable to other reconstructive methods. CONCLUSION: The DBWC is a well described reconstructive method for urinary and fecal diversion utilizing a single stoma following pelvic exenteration. The short- and long-term outcomes following DBWC are comparable to other reconstructive methods and the quality of life with a DBWC is acceptable. DBWC should remain a readily available option for reconstruction following pelvic exenteration.

Exploring the Chemistry of the Mechanical Bond: Synthesis of a [2]Rotaxane through Multicomponent Reactions.

The synthesis of a [2]rotaxane through three- or five-component coupling reactions has been adapted to an organic chemistry experiment for upper-division students. The experimental procedure addresses the search for the most favorable reaction conditions for the synthesis of the interlocked compound, which is obtained in a yield of up to 71%. Moreover, the interlocked nature of the rotaxane is proven by NMR spectroscopy. The content of the sessions has been designed on the basis of a proactive methodology whereby upper-division undergraduate students have a dynamic role. The laboratory experience not only introduces students to the chemistry of the mechanical bond but also reinforces their previous knowledge of basic organic laboratory procedures and their skills with structural elucidation techniques such as NMR and FT-IR spectroscopies. The experiment has been designed in such a customizable way that both experimental procedures and laboratory material can be adapted to a wide range of undergraduate course curricula.

Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice.

Nicotinamide adenine dinucleotide (NAD+ ) homeostasis is constantly compromised due to degradation by NAD+ -dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.

Environmental Enrichment Differentially Activates Neural Circuits in FVB/N Mice, Inducing Social Interaction in Females but Agonistic Behavior in Males.

Environmental enrichment induces behavioral and structural modifications in rodents and influences the capability of mice to cope with stress. However, little is understood about hippocampal neurogenesis and the appearance of social/agonistic (aggressive) behavior upon activation of different neuronal circuits in FVB/N mice. Thus, in this study we hypothesized that environmental enrichment differentially regulates neurogenesis, neural circuit activation and social/agonistic behavior in male and female FVB/N mice. We explored the (1) neurogenic process as an indicative of neuroplasticity, (2) neuronal activation in the limbic system, and (3) social behavior using the resident-intruder test. On postnatal day 23 (PD23), mice were assigned to one of two groups: Standard Housing or Environmental Enrichment. At PD53, rodents underwent the resident-intruder test to evaluate social behaviors. Results revealed that environmental enrichment increased neurogenesis and social interaction in females. In males, environmental enrichment increased neurogenesis and agonistic behavior. Enriched male mice expressed higher levels of agonistic-related behavior than female mice housed under the same conditions. Neural circuit analysis showed lower activation in the amygdala of enriched males and higher activation in enriched females than their respective controls. Enriched females also showed higher activation in the frontal cortex without differences in male groups. Moreover, the insular cortex was less activated in females than in males. Thus, our results indicate that environmental enrichment has different effects on neuroplasticity and social/agonistic behavior in FVB/N mice, suggesting the relevance of sexual dimorphism in response to environmental stimuli.

Administration of an Anal Bulking Agent With Polyacrylate-Polyalcohol Copolymer Particles Versus Endoanal Electrical Stimulation With Biofeedback for the Management of Mild and Moderate Anal Incontinence: A Randomized Prospective Study.

BACKGROUND: There are few treatment options for mild-to-moderate anal incontinence with isolated internal anal sphincter defects or anal incontinence without muscle damage. Less-invasive techniques are generally favored. OBJECTIVE: To compare the results between the use of an anal bulking agent with polyacrylate-polyalcohol copolymer particles and endoanal electrical stimulation with biofeedback in patients with mild or moderate anal incontinence. DESIGN: This was a prospective parallel-group, single-institution, randomized clinical trial. SETTINGS: This study was conducted in an ambulatory setting at the Colorectal Physiology Service of the Hospital das Clinicas, Medical School, University of Sao Paulo. PATIENTS: This study included patients who had anal incontinence for >6 months with isolated internal anal sphincter muscle damage or absence of anatomical defects in the anorectal sphincter complex. INTERVENTIONS: Anal bulking agent and endoanal electrical stimulation with biofeedback. MAIN OUTCOME MEASURES: The primary outcome measure was the Cleveland Clinic Florida Fecal Incontinence Score, and the secondary outcome measures included quality of life, recommended procedures, and anorectal manometry. RESULTS: There were no significant between-group differences in mean age, sex, BMI, stool consistency, and Cleveland Clinic Florida Fecal Incontinence Score (p = 0.20) at baseline. After 12 months, the Cleveland Clinic Florida Fecal Incontinence Score was found to be significantly improved in patients treated with the bulking agent compared to those treated with electrical stimulation (mean, 6.2 vs 9.2; p = 0.002), though the anorectal manometry parameters did not change significantly. The mean anal Cleveland Clinic Florida Fecal Incontinence Score declined by 4.2 points in the bulking agent group compared to a decline of 0.8 in the electrical stimulation group (mean difference in decline: 3.4 points; 95% CI, 1.2-5.5). Quality-of life evaluation showed similar results between groups comparing baseline parameters with 12-month follow-up. LIMITATIONS: The short follow-up period of 1 year, atypical method of biofeedback, and unmatched baseline in some of the quality-of-life scales between the 2 groups limited this study. CONCLUSIONS: In patients with mild or moderate anal incontinence, the Cleveland Clinic Florida Fecal Incontinence Score significantly improved in the bulking agent with polyacrylate-polyalcohol copolymer group compared with the endoanal electrical stimulation with biofeedback group. See Video Abstract at http://links.lww.com/DCR/B938. ADMINISTRACIN DE UN GEL ANAL CON PARTCULAS DE COPOLMERO DE POLIACRILATOPOLIALCOHOL VERSUS ESTIMULACIN ELCTRICA ENDOANAL CON EJERCICIOS ANALES BIOFEEDBACK PARA EL MANEJO DE LA INCONTINENCIA ANAL LEVE Y MODERADA UN ESTUDI PROSPECTIVO ALEATORIZADO: ANTECEDENTES:Hasta la fecha, existen pocas opciones de tratamiento para la incontinencia anal de leve a moderada con defectos aislados del esfínter anal interno o la incontinencia anal sin daño muscular. Por lo general, se prefieren técnicas menos invasivas.OBJETIVO:El objetivo fue comparar los resultados entre el uso de un gel intra-anal con partículas de copolímero de poliacrilato-polialcohol y la estimulación eléctrica endoanal con ejercicios anales en pacientes con incontinencia anal leve o moderada.DISEÑO:Este fue un ensayo clínico aleatorio prospectivo de grupos paralelos, de una institución, realizado en cuatro etapas: base, procedimientos, postratamiento temprano y tardío.AJUSTE:Este estudio se realizó en el ambulatorio de Fisiología Colorrectal del Servicio de Coloproctología del Hospital das Clínicas, Facultad de Medicina, Universidad de São Paulo.PACIENTES:Paciente con incontinencia anal con más de 6 meses, con daño muscular aislado del esfínter anal interno o ausencia de defectos anatómicos en el esfínter anorrectal.INTERVENCIONES:Las intervenciones incluyeron la inyección del gel intra-anal y estimulación eléctrica endoanal con ejercicios anales.PRINCIPALES MEDIDAS DE RESULTADO:Indice de incontinencia fecal (Cleveland Clinic Florida), Indice de calidad de vida, los procedimientos recomendados y la manometría anorrectal.RESULTADOS:No hubo diferencias significativas entre los grupos en cuanto a la edad media, el sexo, el índice de masa corporal, la consistencia de las heces y la puntuación de incontinencia fecal (p = 0,20) al inicio del estudio. Después de 12 meses, la puntuación de incontinencia fecal mejoró significativamente en los pacientes tratados con el el gel intra-anal (media = 6,2) en comparación con los tratados con estimulación eléctrica (media = 9,2; p = 0,002), aunque los parámetros de manometría anorrectal no mejoraron significativamente. La puntuación anal media de incontinencia fecal disminuyó 4,2 puntos en el grupo del Gel intra-anal en comparación con 0,8 en el grupo de estimulación eléctrica (diferencia media en la disminución: 3,4 puntos; IC del 95%: 1,2 a 5,5). La evaluación de la calidad de vida mostró resultados similares entre los grupos que compararon los parámetros iniciales con un seguimiento de 12 meses.LIMITACIONES:Breve período de seguimiento de un año, métodos diferentes de ejercicios anales y línea de base sin igual en algunas de las escalas de calidad de vida entre los dos grupos.CONCLUSIONES:En pacientes con incontinencia anal leve y moderada, la puntuación de incontinencia fecal mejoró significativamente en el grupo de gel intra-anal con copolímero de poliacrilato-polialcohol en comparación con la estimulación eléctrica endoanal. Consulte Video Resumen en http://links.lww.com/DCR/B938. (Traducción- Dr Leonardo Alfonso Bustamante-Lopez).

Outcomes of Patients With Local Regrowth After Nonoperative Management of Rectal Cancer After Neoadjuvant Chemoradiotherapy.

BACKGROUND: Clinical complete responders after chemoradiation for rectal cancer are increasingly being managed by a watch-and-wait strategy. Nonetheless, a significant proportion will experience a local regrowth, and the long-term oncological outcomes of these patients is not totally known. OBJECTIVE: The purpose of this study was to analyze the outcomes of patients who submitted to a watch-and-wait strategy and developed a local regrowth, and to compare these results with sustained complete clinical responders. DESIGN: This was a retrospective study. SETTING: Single institution, tertiary cancer center involved in alternatives to organ preservation. PATIENTS: Patients with a biopsy-proven rectal adenocarcinoma (stage II/III or low lying cT2N0M0 at risk for an abdominoperineal resection) treated with chemoradiation who were found at restage to have a clinical complete response. INTERVENTIONS: Rectal cancer patients treated with chemoradiation who underwent a watch-and-wait strategy (without a full thickness local excision) and developed a local regrowth were compared to the remaining patients of the watch-and-wait strategy. MAIN OUTCOME MEASURES: Overall survival between groups, incidence of regrowth' and results of salvage surgery. RESULTS: There were 67 patients. Local regrowth occurred in 20 (29.9%) patients treated with a watch-and-wait strategy. Mean follow-up was 62.7 months. Regrowth occurred at mean 14.2 months after chemoradiation, half of them within the first 12 months. Patients presented with comparable initial staging, lateral pelvic lymph-node metastasis, and extramural venous invasion. The regrowth group had a statistically nonsignificant higher incidence of mesorectal fascia involvement (35.0% vs 13.3%, p = 0.089). All regrowths underwent salvage surgery, mostly (75%) a sphincter-sparing procedure. 5-year overall survival was 71.1% in patients with regrowth and 91.1% in patients with a sustained complete clinical response (p = 0.027). LIMITATIONS: This study was limited by its retrospective evaluation of patient selection for a watch-and-wait strategy and outcomes, as well as its small sample size. CONCLUSIONS: Local regrowth is a frequent event when following a watch-and-wait policy (29.9%); however, patients could undergo salvage surgical treatment with adequate pelvic control. In this series, overall survival showed a statistically significant difference from patients managed with a watch-and-wait strategy who experienced a local regrowth compared to those who did not. See Video Abstract at http://links.lww.com/DCR/B773.RESULTADOS DE LOS PACIENTES CON REBROTE LOCAL, DESPUÉS DEL MANEJO NO QUIRÚRGICO DEL CÁNCER DE RECTO, DESPUÉS DE LA QUIMIORRADIOTERAPIA NEOADYUVANTEANTECEDENTES:Los respondedores clínicos completos, después de la quimiorradiación para el cáncer de recto, se tratan cada vez más mediante una estrategia de observación y espera. No obstante, una proporción significativa experimentará un rebrote local y los resultados oncológicos a largo plazo de estos pacientes, no se conocen por completo.OBJETIVO:El propósito de este estudio, fue analizar los resultados de los pacientes sometidos a una estrategia de observación y espera, que desarrollaron un rebrote local, y comparar estos resultados con respondedores clínicos completos sostenidos.DISEÑO:Este fue un estudio retrospectivo.ENTORNO CLINICO.Institución única, centro oncológico terciario involucrado en alternativas a la preservación de órganos.PACIENTES:Pacientes con un adenocarcinoma de recto comprobado por biopsia (estadio II / III o posición baja cT2N0M0, en riesgo de resección abdominoperineal), tratados con quimiorradiación, y que durante un reestadiaje, presentaron una respuesta clínica completa.INTERVENCIONES:Los pacientes con cáncer de recto tratados con quimiorradiación, sometidos a una estrategia de observación y espera (sin una escisión local de espesor total) y que desarrollaron un rebrote local, se compararon con los pacientes restantes de la estrategia de observación y espera.PRINCIPALES MEDIDAS DE VALORACION:Supervivencia global entre los grupos, incidencia de rebrote y resultados de la cirugía de rescate.RESULTADOS:Fueron 67 pacientes. El rebrote local ocurrió en 20 (29,9%) pacientes tratados con una estrategia de observación y espera. El seguimiento medio fue de 62,7 meses. El rebrote se produjo a la media de 14,2 meses después de la quimiorradiación, la mitad de ellos dentro de los primeros 12 meses. Los pacientes se presentaron con una estadificación inicial comparable, metástasis en los ganglios linfáticos pélvicos laterales e invasión venosa extramural. El grupo de rebrote tuvo una mayor incidencia estadísticamente no significativa de afectación de la fascia mesorrectal (35,0 vs 13,3%, p = 0,089). Todos los rebrotes se sometieron a cirugía de rescate, en su mayoría (75%) con procedimiento de preservación del esfínter. La supervivencia global a 5 años fue del 71,1% en pacientes con rebrote y del 91,1% en pacientes con una respuesta clínica completa sostenida (p = 0,027).LIMITACIONES:Evaluación retrospectiva de la selección de pacientes para una estrategia y resultados de observar y esperar, tamaño de muestra pequeño.CONCLUSIONES:El rebrote local es un evento frecuente después de la política de observación y espera (29,9%), sin embargo los pacientes podrían someterse a un tratamiento quirúrgico de rescate con un adecuado control pélvico. En esta serie, la supervivencia global mostró una diferencia estadísticamente significativa de los pacientes manejados con una estrategia de observación y espera que experimentaron un rebrote local, en comparación con los que no lo hicieron. Consulte Video Resumen en http://links.lww.com/DCR/B773. (Traducción-Dr. Fidel Ruiz Healy).

Ring-to-Thread Chirality Transfer in [2]Rotaxanes for the Synthesis of Enantioenriched Lactams.

The synthesis of chiral mechanically interlocked molecules has attracted a lot of attention in the last few years, with applications in different fields, such as asymmetric catalysis or sensing. Herein we describe the synthesis of orientational mechanostereoisomers, which include a benzylic amide macrocycle with a stereogenic center, and nonsymmetric N-(arylmethyl)fumaramides as the axis. The base-promoted cyclization of the initial fumaramide thread allows enantioenriched value-added compounds, such as lactams of different ring sizes and amino acids, to be obtained. The chiral information is effectively transmitted across the mechanical bond from the encircling ring to the interlocked lactam. High levels of enantioselectivity and full control of the regioselectivity of the final cyclic compounds are attained.

The capacity of differentiation of stromal vascular fraction cells into beige adipocytes is markedly reduced in subjects with overweight/obesity and insulin resistance: effect of genistein.

BACKGROUND: Dietary bioactive compounds have been demonstrated to produce several health benefits. Genistein, an isoflavone of soy protein, and resveratrol, a polyphenol from grapes, have been shown to improve insulin sensitivity and to stimulate white adipose tissue (WAT) browning, leading to increased energy expenditure. However, it has not been demonstrated in humans whether genistein or resveratrol have the capacity to stimulate the differentiation of stromal vascular fraction (SVF) cells from white fat into beige adipocytes. SUBJECTS/METHODS: With this aim, we assessed whether stromal vascular fraction cells obtained from biopsies of the subdermal fat depots of subjects with normal body weight (NW) or from subjects with overweight/obesity with (OIR) or without (OIS) insulin resistance were able to differentiate into the beige adipose tissue lineage in vitro, by exposing the cells to genistein, resveratrol, or the combination of both. RESULTS: The results showed that SVF cells obtained from NW or OIS subjects were able to differentiate into beige adipocytes according to an increased expression of beige biomarkers including UCP1, PDRM-16, PGC1α, CIDEA, and SHOX2 upon exposure to genistein. However, SVF cells from OIR subjects were unable to differentiate into beige adipocytes with any of the inducers. Exposure to resveratrol or the combination of resveratrol/genistein did not significantly stimulate the expression of browning markers in any of the groups studied. We found that the non-responsiveness of the SVF from subjects with obesity and insulin resistance to any of the inducers was associated with an increase in the expression of endoplasmic reticulum stress markers. CONCLUSION: Consumption of genistein may stimulate WAT browning mainly in NW or OIS subjects. Thus, obesity associated with insulin resistance may be considered as a condition that prevents some beneficial effects of some dietary bioactive compounds.

Short Daily Exposure to Environmental Enrichment, Fluoxetine, or Their Combination Reverses Deterioration of the Coat and Anhedonia Behaviors with Differential Effects on Hippocampal Neurogenesis in Chronically Stressed Mice.

Depression is a neuropsychiatric disorder with a high impact on the worldwide population. To overcome depression, antidepressant drugs are the first line of treatment. However, pre-clinical studies have pointed out that antidepressants are not entirely efficacious and that the quality of the living environment after stress cessation may play a relevant role in increasing their efficacy. As it is unknown whether a short daily exposure to environmental enrichment during chronic stress and antidepressant treatment will be more effective than just the pharmacological treatment, this study analyzed the effects of fluoxetine, environmental enrichment, and their combination on depressive-associated behavior. Additionally, we investigated hippocampal neurogenesis in mice exposed to chronic mild stress. Our results indicate that fluoxetine reversed anhedonia. Besides, fluoxetine reversed the decrement of some events of the hippocampal neurogenic process caused by chronic mild stress. Conversely, short daily exposure to environmental enrichment changed the deterioration of the coat and anhedonia. Although, this environmental intervention did not produce significant changes in the neurogenic process affected by chronic mild stress, fluoxetine plus environmental enrichment showed similar effects to those caused by environmental enrichment to reverse depressive-like behaviors. Like fluoxetine, the combination reversed the declining number of Ki67, doublecortin, calretinin cells and mature newborn neurons. Finally, this study suggests that short daily exposure to environmental enrichment improves the effects of fluoxetine to reverse the deterioration of the coat and anhedonia in chronically stressed mice. In addition, the combination of fluoxetine with environmental enrichment produces more significant effects than those caused by fluoxetine alone on some events of the neurogenic process. Thus, environmental enrichment improves the benefits of pharmacological treatment by mechanisms that need to be clarified.

Analysis of Colombia's Telemedicine Development, the Postconflict Potential Opportunity.

Aims: The goal of this study was to evaluate the development of telemedicine in Colombia. Materials and Methods: Searched for laws in the Colombian legal system; the statistics of services and health operators was extracted from the unique system of habilitation; we looked for reports from the Ministry of Information and Communication Technologies (ICT), the demographic statistics was obtained from the National Administrative Department of Statistics. Data analysis techniques were applied to identify possible relationships between them. Results: In Colombia, since the proclamation of the legality of telemedicine in 2007, there are five laws, five resolutions, and three government plans. A total of 3,245 services have been implemented in telemedicine, distributed throughout the territory by 51,490 operators, the ICT penetration rate is 21.17% by fixed internet and 39.3% by mobile internet; the Colombian population is 49,882,091 people, 25,228,444 women and 24,605,796 men, who are distributed 76.97% in the urban sector and 23.02% in the rural sector, and the coverage of health services is 94.8%. Conclusion: The development of health services in the telemedicine modality has been driven by Colombian regulations since 2007 and the plans for the growth of ICT infrastructure since 2009; however, these services have not yet reached 100% of the territory, especially areas with difficult access. The Colombian peace agreement creates the National Rural Health Plan (PNSR), which is presented as the obligation to carry out health coverage in all the territories, especially those in the rural areas, for the implementation of the strategy related to the implementation of services in telemedicine.

Melatonin Modulates Dendrite Maturation and Complexity in the Dorsal- and Ventral- Dentate Gyrus Concomitantly with Its Antidepressant-Like Effect in Male Balb/C Mice.

Adult neurogenesis occurs in the dentate gyrus (DG) of the hippocampus. New neurons help to counteract the effects of stress and several interventions including antidepressant drugs, environmental modifications and internal factors act pro-neurogenic with consequences in the dorsal and ventral DG. Melatonin, the main product synthesized by the pineal gland, induces antidepressant-like effects and modulates several events of the neurogenic process. However, the information related to the capability of melatonin to modulate dendrite maturation and complexity in the dorsal and ventral regions of the DG and their correlation with its antidepressant-like effect is absent. Thus, in this study, we analyzed the impact of melatonin (0, 0.5, 1, 2.5, 5 or 10 mg/kg) administered daily for fourteen days on the number, dendrite complexity and distribution of doublecortin (DCX)-cells in the dorsal-ventral regions of the DG in male Balb/C mice. Doublecortin is a microtubule-associated protein that is expressed during the course of dendritic maturation of newborn neurons. Also, we analyzed the impact of melatonin on despair-like behavior in the forced swim test. We first found a significant increase in the number and higher dendrite complexity, mainly with the doses of 2.5, 5 and 10 mg/kg of melatonin (81%, 122%, 78%). These cells showed more complex dendritic trees in the ventral- and the dorsal- DG. Concomitantly, the doses of 5 and 10 mg/kg of melatonin decreased depressant-like behavior (76%, 82%). Finally, the data corroborate the antidepressant-like effect of melatonin and the increasing number of doublecortin-associated cells. Besides, the data indicate that melatonin favors the number and dendrite complexity of DCX-cells in the dorsal- and ventral- region of the DG, which may explain part of the antidepressant-like effect of melatonin.

Goat's Milk Intake Prevents Obesity, Hepatic Steatosis and Insulin Resistance in Mice Fed A High-Fat Diet by Reducing Inflammatory Markers and Increasing Energy Expenditure and Mitochondrial Content in Skeletal Muscle.

Goat's milk is a rich source of bioactive compounds (peptides, conjugated linoleic acid, short chain fatty acids, monounsaturated and polyunsaturated fatty acids, polyphenols such as phytoestrogens and minerals among others) that exert important health benefits. However, goat's milk composition depends on the type of food provided to the animal and thus, the abundance of bioactive compounds in milk depends on the dietary sources of the goat feed. The metabolic impact of goat milk rich in bioactive compounds during metabolic challenges such as a high-fat (HF) diet has not been explored. Thus, we evaluated the effect of milk from goats fed a conventional diet, a conventional diet supplemented with 30% Acacia farnesiana (AF) pods or grazing on metabolic alterations in mice fed a HF diet. Interestingly, the incorporation of goat's milk in the diet decreased body weight and body fat mass, improved glucose tolerance, prevented adipose tissue hypertrophy and hepatic steatosis in mice fed a HF diet. These effects were associated with an increase in energy expenditure, augmented oxidative fibers in skeletal muscle, and reduced inflammatory markers. Consequently, goat's milk can be considered a non-pharmacologic strategy to improve the metabolic alterations induced by a HF diet. Using the body surface area normalization method gave a conversion equivalent daily human intake dose of 1.4 to 2.8 glasses (250 mL per glass/day) of fresh goat milk for an adult of 60 kg, which can be used as reference for future clinical studies.

T≤2N0 TRG1-2 in Post-Chemoradiation Therapy MRI: What can it Predict?

BACKGROUND: Total mesorectal excision is the standard radical operation after neoadjuvant chemoradiotherapy for patients with middle/low locally advanced rectal cancer. However, it carries significant rates of morbidity, sexual/urinary dysfunction, fecal impairment and permanent stoma. The ability to identify patients with a complete or nearly-complete response could help steer patients to less-invasive surgery or a watch-and-wait strategy. OBJECTIVE: To assess the ability to predict good responders and a favorable prognosis among rectal cancer patients by post-chemoradiation therapy MRI. PATIENTS: Consecutive patients stage T3-4N0M0 or T(any)N+M0 located within 10cm from the anal verge were enrolled. Patients were staged and re-staged 8.8 weeks after the completion of chemoradiation by digital exam, colonoscopy, pelvic-MRI, and thorax and abdominal CT scans. All patients underwent total mesorectal excision with curative intent. RESULTS: Of the total 309 patients, 275 were eligible, and 199 (72.4%) of these were stage III. Restaging-MRI identified 59 (21.4%) T=2N0/TRG1-2. Specimen pathologic evaluation revealed 43 (15.6%) patients with a complete pathologic response. Estimates of the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of MRIyT=2N0/TRG1-2 for the identification of ypT0N0 were 79.7%, 84.5%, 53.5%, 39%, and 90.7%, respectively. Estimates for the identification of ypN0 were 48.4%, 27.8%, 92%, 88.1%, and 48.4%, respectively. In a multivariate analysis, the only pre-CRT/MRI variables that were associated with an increased risk of lymph node involvement at the specimen were N+ (OR=2.22) and extramural vascular invasion (OR=2.28). MRI yT=2N0/TRG1-2 patients showed improved estimated 5-year disease-free survival, but no difference in estimated 5-year survival. CONCLUSION: Although MRIyT=2N0/TRG1-2 cannot predict all cases of a complete pathologic response, it can effectively predict a low rate of lymph node involvement and a better prognosis in patients who undergo total mesorectal excision.

Adiponectin synthesis and secretion by subcutaneous adipose tissue is impaired during obesity by endoplasmic reticulum stress.

Subcutaneous (SAT) and visceral (VAT) adipose tissues stores excess energy as triglycerides and synthesize adiponectin to prevent ectopic lipid accumulation and lipotoxicity. During obesity, an impairment in the capacity of SAT to store triglycerides and synthesize adiponectin is associated with increased free fatty acids (FFA) release, leading to VAT hypertrophy and hepatic and skeletal muscle lipotoxicity. Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may be involved in SAT dysfunction during obesity. The objectives of this study were to assess UPR activation and adiponectin synthesis in: 1) SAT and VAT from mice exposed to acute pharmacologic or chronic obesity-induced ER stress and in 2) cultured mice primary mature adipocytes or adipocytes differentiated in vitro from SAT and VAT exposed to tunicamycin or thapsigargin. Mice fed a high-fat diet developed obesity, increased FFA and lower circulating adiponectin in association with lower adiponectin synthesis and increased UPR markers in SAT. Mice subjected to acute ER stress by pioglitazone administration and a low-dose tunicamycin injection presented a maladaptive UPR activation in SAT along with reduced adiponectin synthesis and secretion and increased lipolysis with respect to VAT, associated with lipid accumulation in skeletal muscle and liver. Primary adipocytes and adipocytes differentiated from SAT exposed to pharmacologic ER stress also developed maladaptive UPR, along with reduced adiponectin synthesis and increased lipolysis with respect to those from VAT. Our results indicate that compared to VAT, SAT is more susceptible to ER stress, leading to increased lipolysis and reduced adiponectin synthesis and secretion.