Diverticulitis with abscess formation: Outcomes of non-operative management and nomogram for predicting emergency surgery: The Diplicab Study Collaborative Group.

BACKGROUND: To assess short- and long-term outcomes from non-surgical management of diverticulitis with abscess formation and to develop a nomogram to predict emergency surgery. METHODS: This nationwide retrospective cohort study was performed in 29 Spanish referral centers, including patients with a first episode of a diverticular abscess (modified Hinchey Ib-II) from 2015 to 2019. Emergency surgery, complications, and recurrent episodes were analyzed. Regression analysis was used to assess risk factors, and a nomogram for emergency surgery was designed. RESULTS: Overall, 1,395 patients were included (1,078 Hinchey Ib and 317 Hinchey II). Most (1,184, 84.9%) patients were treated with antibiotics without percutaneous drainage, and 194 (13.90%) patients required emergency surgery during admission. Percutaneous drainage (208 patients) was associated with a lower risk of emergency surgery in patients with abscesses of ≥5 cm (19.9% vs 29.3%, P = .035; odds ratio 0.59 [0.37-0.96]). The multivariate analysis showed that immunosuppression treatment, C-reactive protein (odds ratio: 1.003; 1.001-1.005), free pneumoperitoneum (odds ratio: 3.01; 2.04-4.44), Hinchey II (odds ratio: 2.15; 1.42-3.26), abscess size 3 to 4.9 cm (odds ratio: 1.87; 1.06-3.29), abscess size ≥5 cm (odds ratio: 3.62; 2.08-6.32), and use of morphine (odds ratio: 3.68; 2.29-5.92) were associated with emergency surgery. A nomogram was developed with an area under the receiver operating characteristic curve of 0.81 (95% confidence interval: 0.77-0.85). CONCLUSION: Percutaneous drainage must be considered in abscesses ≥5 cm to reduce emergency surgery rates; however, there are insufficient data to recommend it in smaller abscesses. The use of the nomogram could help the surgeon develop a targeted approach.

Progression in Time of Dentate Gyrus Granule Cell Layer Widening due to Excitotoxicity Occurs along In Vivo LTP Reinstatement and Contextual Fear Memory Recovery.

The dentate gyrus (DG) is the gateway of sensory information arriving from the perforant pathway (PP) to the hippocampus. The adequate integration of incoming information into the DG is paramount in the execution of hippocampal-dependent cognitive functions. An abnormal DG granule cell layer (GCL) widening due to granule cell dispersion has been reported under hyperexcitation conditions in animal models as well as in patients with mesial temporal lobe epilepsy, but also in patients with no apparent relation to epilepsy. Strikingly, it is unclear whether the presence and severity of GCL widening along time affect synaptic processing arising from the PP and alter the performance in hippocampal-mediated behaviors. To evaluate the above, we injected excitotoxic kainic acid (KA) unilaterally into the DG of mice and analyzed the evolution of GCL widening at 10 and 30 days post injection (dpi), while analyzing if KA-induced GCL widening affected in vivo long-term potentiation (LTP) in the PP-DG pathway, as well as the performance in learning and memory through contextual fear conditioning. Our results show that at 10 dpi, when a subtle GCL widening was observed, LTP induction, as well as contextual fear memory, were impaired. However, at 30 dpi when a pronounced increase in GCL widening was found, LTP induction and contextual fear memory were already reestablished. These results highlight the plastic potential of the DG to recover some of its functions despite a major structural alteration such as abnormal GCL widening.

Improved post-stroke spontaneous recovery by astrocytic extracellular vesicles.

Spontaneous recovery after a stroke accounts for a significant part of the neurological recovery in patients. However limited, the spontaneous recovery is mechanistically driven by axonal restorative processes for which several molecular cues have been previously described. We report the acceleration of spontaneous recovery in a preclinical model of ischemia/reperfusion in rats via a single intracerebroventricular administration of extracellular vesicles released from primary cortical astrocytes. We used magnetic resonance imaging and confocal and multiphoton microscopy to correlate the structural remodeling of the corpus callosum and striatocortical circuits with neurological performance during 21 days. We also evaluated the functionality of the corpus callosum by repetitive recordings of compound action potentials to show that the recovery facilitated by astrocytic extracellular vesicles was both anatomical and functional. Our data provide compelling evidence that astrocytes can hasten the basal recovery that naturally occurs post-stroke through the release of cellular mediators contained in extracellular vesicles.

BDNF induces in vivo long-lasting enhancement of synaptic transmission and structural reorganization at the hippocampal mossy fibers in a transcription and translation-independent manner.

Brain-derived neurotrophic factor (BDNF) is an essential product of protein synthesis with a prominent impact on brain signaling and synaptic plasticity. Exogenous application of this neurotrophin is able to induce long-term potentiation (LTP) in several brain structures such as the hippocampus along with increases in gene transcription and translation of proteins involved in functional and structural plasticity. In this regard, our previous studies have demonstrated that acute intrahippocampal administration of BDNF induces long-lasting enhancement of synaptic transmission at the mossy fibers projection (MF) accompanied by a structural reorganization at the CA3 hippocampus area. Thus, considering the non-canonical molecular mechanisms underlying MF-CA3-LTP and the high expression of this neurotrophin in the CA3 area, we wonder whether transcriptional and translational inhibition interferes with the persistence of the MF functional and structural synaptic plasticity elicited by BDNF in adult rats in vivo. Our results show that BDNF is able to induce a lasting potentiation of synaptic efficacy at the MF projection accompanied by a structural reorganization at the CA3 area in an mRNA synthesis and protein translation-independent manner. The present findings support the idea that BDNF is an essential plasticity related product, which is necessary and sufficient to induce and maintain functional and structural synaptic plasticity at the MF-CA3 pathway.

Can invasive breast carcinoma with close or positive margins be managed without a new surgery?

We present the long-term outcome (FU 127 months) of a prospective study with 248 breast cancer patients with close or positive surgical margin, treated with 50 Gy whole breast irradiation plus high-dose-rate boost, 3 × 4.4 Gy. Actuarial breast failure at 10/15 years was 6.5%/11.6%; with positive margin (120) 6.8%/14.8%, with margin ≤2 mm (76) 9.8%/9.8%, with margin >2 mm <5 mm (52) 2%/2%. In 90 patients aged ≤50 was 11.9%/17.8%, between 51 and 70, 3.8%/8.2%, >70, 0%. Fibrosis appeared in 26.7%. Cosmetic outcome was excellent/good in 85.8%. This approach avoids a second surgery in women >50 with positive surgical margin, or with close margins in all ages.

Bidirectional modulation of taste aversion extinction by insular cortex LTP and LTD.

The history of activity of a given neuron has been proposed to bidirectionally influence its future response to synaptic inputs. In particular, induction of synaptic plasticity expressions such as long-term potentiation (LTP) and long-term depression (LTD) modifies the performance of several behavioral tasks. Our previous studies in the insular cortex (IC), a neocortical region that has been related to acquisition and retention of conditioned taste aversion (CTA), have demonstrated that induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC pathway before CTA training enhances the retention of this task. In addition, we reported that CTA training triggers a persistent impairment in the ability to induce in vivo LTP in the IC. The aim of the present study was to investigate whether LTD can be induced in the Bla-IC projection in vivo, as well as, whether the extinction of CTA is bidirectionally modified by previous synaptic plasticity induction in this pathway. Thus, rats received 900 train pulses (five 250µs pulses at 250Hz) delivered at 1Hz in the Bla-IC projection in order to induce LTD or 10 trains of 100Hz/1s with an intertrain interval of 20s in order to induce LTP. Seven days after surgery, rats were trained in the CTA task including the extinction trials. Our results show that the Bla-IC pathway is able to express in vivo LTD in an N-Methyl-D-aspartate (NMDA) receptor-dependent manner. Induction of LTD in the Bla-IC projection previous to CTA training facilitates the extinction of this task. Conversely, LTP induction enhances CTA retention. The present results show the bidirectional modulation of CTA extinction in response to IC-LTP and LTD, providing evidence of the homeostatic adaptation of taste learning.

Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory.

Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace.

High-dose-rate brachytherapy boost effect on local tumor control in young women with breast cancer.

PURPOSE: To evaluate the local control rate and complications of a single fraction of high-dose-rate brachytherapy (HDR BT) boost in women aged 45 yeas and younger after breast-conserving therapy. METHODS AND MATERIALS: Between 1999 and 2007, 167 patients between the ages of 26 and 45 years old (72 were 40 years old or younger), with stages T1 to T2 invasive breast cancer with disease-free margin status of at least 5 mm after breast-conserving surgery received 46 to 50 Gy whole-breast irradiation plus a 7-Gy HDR-BT boost ("fast boost"). An axillary dissection was performed in 72.5% of the patients and sentinel lymph node biopsy in 27.5%. A supraclavicular area was irradiated in 19% of the patients. Chemotherapy was used in 86% of the patients and hormone treatment in 77%. Clinical nodes were present in 18% and pathological nodes in 29%. The pathological stage was pT0: 5%, pTis: 3%, pT1: 69% and pT2: 23%. Intraductal component was present in 40% and 28% were G3. RESULTS: At a median follow-up of 92 months, 9 patients relapsed on the margin of the implant, and 1 patient in another quadrant, resulting in a 10-year local relapse rate of 4.3% and a breast relapse rate of 4.9%, with breast preservation in 93.4%; no case of mastectomy due to poor cosmesis arose. Actuarial 5- and 10-year disease-free, cause-specific, and overall survival rates were 87.9% and 85.8%, and 92.1% and 88.4%, and 92.1% and 87.3%, respectively. In a univariate analysis, triple-negative cases and negative hormone receptors did worse, but in a multivariate analysis, only the last factor was significant for local and breast control. Asymptomatic fibrosis G2 was recorded in 3 cases, and there were no other late complications. Cosmetic results were good to excellent in 97% of cases. CONCLUSIONS: A single dose of 7 Gy using the fast-boost technique is well tolerated, with a low rate of late complications and improved local tumor control in women aged 45 and younger, compared to published data. This approach is recommended in breast-preserving treatment.

Patterns of responding on a balloon analogue task reveal individual differences in overall risk-taking: choice between guaranteed and uncertain cash.

We explored the utility of analyzing within- and between-balloon response patterns on a balloon analogue task (BAT) in relation to overall risk scores, and to a choice between a small guaranteed cash reward and an uncertain reward of the same expected value. Young adults (n = 61) played a BAT, and then were offered a choice between $5 in cash and betting to win $0 to $15. Between groups, pumping was differentially influenced by explosions and by the number of successive unexploded balloons, with risk takers responding increasingly on successive balloons after an explosion. Within-balloons, risk takers showed a characteristic pattern of constant high rate, while non-risk takers showed a characteristic variable lower rate. Overall, results show that the higher number of pumps and explosions that characterize risk takers at a molar level, result from particular forms of adaptation to the positive and negative outcomes of choices seen at a molecular level.

Mejora en el control local en mujeres jóvenes con cáncer de mama precoz añadiendo una sola fracción de braquiterapia de alta tasa de dosis / Improved local control in young women with early-stage breast cancer by adding a single fraction of high-dose-rate brachytherapy

Objetivo. Evaluar la eficacia de la braquiterapia con iridio-192 de alta tasa de dosis con una sola fracción como sobreimpresión después de irradiar la mama en mujeres de hasta 45 años. Pacientes y métodos. Se estudiaron 167 pacientes consecutivas con tumores T1-2, entre 26-45 años, sometidas a cirugía conservadora con bordes libres y radioterapia (46-50 Gy) por carcinoma de mama infiltrante entre 1999 y 2008. Se realizó implante con agujas metálicas paralelas bajo anestesia local y sedación de forma ambulatoria. La quimioterapia se utilizó en el 85% (66% adyuvante, 19% neoadyuvante) y la hormonoterapia en el 77%. Se administró una dosis única de 7 Gy con braquiterapia de alta tasa de dosis (fast-boost). Resultados. El seguimiento mediano fue de 69 meses. Ocho pacientes recayeron en el lecho o en el margen tumoral con un control actuarial local de 95,6% a 10 años (tasa de recaída 4,4%). Hubo una recaída en otro cuadrante, por tanto, el control local en la mama fue de 94,1%. Las pacientes hasta 40 años recayeron en la mama en un 6,9% a los 10 años. Ventidós pacientes desarrollaron metástasis. La supervivencia libre de enfermedad y global fue de 85,5 y 92%, respectivamente. Los resultados cosméticos fueron buenos/excelentes en el 97%. La toxicidad aguda y tardía fueron mínimas. Conclusiones. El fast-boost con una sola fracción es una técnica rápida, sencilla y eficaz cuando los márgenes quirúrgicos están libres. El control local en las mujeres jóvenes se ha mejorado respecto a la literatura, por lo que se recomienda la preservación de la mama con este esquema

Objective. To evaluate the effectiveness of a single fraction of high-dose-rate iridium-192 brachytherapy as a boost after irradiation of the breast in women aged 45 or less. Patients and methods. We studied 167 consecutive patients with T1-2 tumors, aged between 26 and 45 years undergoing conservative surgery with free margins and radiotherapy (46-50 Gy) for invasive breast carcinoma between 1999 and 2008. Parallel metal needles were implanted under local anesthesia and sedation on an outpatient basis. Chemotherapy was used in 85% (66% adjuvant and 19% neoadjuvant) and hormonal therapy in 77%. A single 7 Gy-dose of high-dose rate brachytherapy ("fast boost") was administered. Results. The median follow-up was 69 months. In 8 patients, recurrences occurred in the tumor bed or in the margin with an actuarial local control of 95.6% at 10 years (relapse rate 4.4%). There was a relapse in another quadrant and therefore breast control was 94.1%. In patients aged up to 40 years, the breast failure rate was 6.9% at 10 years. Metastases developed in 22 patients. Disease-free survival was 85.5% and overall survival was 92%. Cosmetic results were good or excellent in 97% and acute and late toxicity was minimal. Conclusions. The fast boost technique with a single fraction is fast, simple, and effective when surgical margins are free. Local control in young women has improved compared with prior reports in the literature. Therefore, this technique can be recommended for breast preservation

Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement.

It has been proposed that long-term memory (LTM) persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related LTM when protein synthesis was inhibited. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that intracortical delivery of BDNF reverses the deficit in CTA memory caused by the inhibition of IC protein synthesis due to anisomycin administration during early acquisition. In this work, we first analyze whether CTA memory storage is protein synthesis-dependent in different time windows. We observed that CTA memory become sensible to protein synthesis inhibition 5 and 7 h after acquisition. Then, we explore the effect of BDNF delivery (2 µg/2 µl per side) in the IC during those late protein synthesis-dependent phases. Our results show that BDNF reverses the CTA memory deficit produced by protein synthesis inhibition in both phases. These findings support the notion that recurrent rounds of consolidation-like events take place in the neocortex for maintenance of CTA memory trace and that BDNF is an essential component of these processes.

Fracturas pélvicas por insuficiencia tras radioterapia. Diagnóstico mediante TC / Pelvic insufficiency fractures following radiotherapy. CT Diagnosis

Objetivo: Determinar la utilidad de la tomografía computarizada (TC) como método de elección para establecer el diagnóstico definitivo de fracturas pélvicas por insuficiencia (FIP) frente al de enfermedad ósea metastásica en pacientes oncológicos tratados con radioterapia. Material y métodos: Valoración de las TC pélvicas de 26 pacientes oncológicos que presentaron sintomatología aguda referida como dolor lumbar. Los hallazgos de TC recogidos fueron: esclerosis, línea de fractura y masa de partes blandas. Se correlacionaron con los estudios gammagráficos y se compararon con las TC previas. Se realizó además seguimiento clinicorradiológico. Resultados: Todos los pacientes fueron diagnosticados de forma correcta de fracturas por insuficiencia pélvica mediante estudio por TC de pelvis. Los estudios por TC mostraron esclerosis en todos los casos (100 por ciento); líneas de fractura sacras en 16 (65 por ciento) casos; fracturas púbicas (30 por ciento) en ocho casos; masa de partes blandas en los cinco casos de fractura sinfisal bilateral. Se pudo establecer seguimiento en 21 pacientes, y la TC mostró: ausencia de visualización de las líneas de fractura, tendencia a la normalización con disminución progresiva de la esclerosis y pocos cambios en las fracturas de la sínfisis púbica. Conclusión: La TC es la técnica de imagen de elección para establecer el diagnóstico definitivo de FIP. Conocer esta entidad y ser capaz de diagnosticarla correctamente permite realizar el tratamiento adecuado y evitar la realización de pruebas diagnósticas y terapéuticas innecesarias, costosas y en ocasiones contraindicadas (AU)