Assessing the impact of pregnancy planning on obstetric and perinatal outcomes in women with pregestational diabetes mellitus.

AIMS: We investigated the role of pregnancy planning in improving glycemic control and its potential impact on the overall pregnancy outcomes, obstetric outcomes, and perinatal well-being in women with pregestational diabetes mellitus (PGDM). METHODS: A retrospective observational cohort study was conducted, including all pregnant women with PGDM treated in our center 2012 and 2018. RESULTS: Among 425 participants, 26.6 % had planned pregnancies. The lowest rate of pregnancy planning was observed in women with type 2 diabetes mellitus (6.5 %). Women with planned pregnancies had lower BMI. Both pregestational HbA1c levels (6.66 % vs. 7.61 %, p < 0.001) and HbA1c levels at the first prenatal visit (6.39 % vs. 7.24 %, p < 0.001) were significantly lower in the planned pregnancy group. These differences persisted until the end of pregnancy (6.09 % vs. 6.47 %, p = 0.006). Although better glycemic control was associated with a non-significant decrease in fetuses with birth weight over 4000 g (18.1 % vs. 22.1 %) and 4500 g (3.0 % vs. 4.2 %), we did not find significant effects on other morbidity events, maternal outcomes, or the cesarean section rate. CONCLUSIONS: Pregnancy planning in PGDM women improved glycemic control and HbA1c levels. Limited impact on obstetric and perinatal outcomes suggests scope for other focused interventions to optimize maternal and fetal health.

Stereochemical insights into ß-amino-N-acylhydrazones and their impact on DPP-4 inhibition.

Dipeptidyl peptidase IV (DPP-4) is a key enzyme that regulates several important biological processes and it is better known to be targeted by gliptins as a modern validated approach for the management of type 2 diabetes mellitus (T2DM). However, new generations of DPP-4 inhibitors capable of controlling inflammatory processes associated with chronic complications of T2DM are still needed. In this scenario, we report here the design by molecular modelling of new ß-amino-N-acylhydrazones, their racemic synthesis, chiral resolution, determination of physicochemical properties and their DPP4 inhibitory potency. Theoretical and experimental approaches allowed us to propose a preliminary SAR, as well as to identify LASSBio-2124 (6) as a new lead for DPP-4 inhibition, with good physicochemical properties, favourable eudismic ratio, scalable synthesis and anti-diabetes effect in a proof-of-concept model. These findings represent an interesting starting point for the development of a new generation of DPP-4 inhibitors, useful in the treatment of T2DM and comorbidities.

Outcomes following formation of a dedicated pediatric liver transplant anesthesia team.

BACKGROUND: Given the complex nature of liver transplant surgery, adult centers typically use a dedicated liver transplant anesthesia team, which has improved patient outcomes. AIMS: Our goal was to determine whether a dedicated pediatric liver transplant anesthesia team was associated with improved patient outcomes. METHODS: This retrospective cohort study analyzed patients who underwent liver transplantation from April 2013 to September 2020 at St. Louis Children's Hospital. The general group (April 2013-December 2016) was compared with the liver group (January 2017-September 2020). Outcomes measured included cases per anesthesiologist, early extubation, ventilator days, fluid and blood administration, postoperative events, and intensive care unit and hospital length of stay (LOS). RESULTS: Patients in both groups had similar demographics. The average number of cases/anesthesiologist/year was 2.9 times higher in the liver group (mean (SD) general 0.7 (0.5), liver 2.0 (0.6), and difference in mean [95% CI] 1.3 [0.8, 1.8]). The rate of extubation in the operating room was higher for patients in the liver group (general 56%, liver 80%, and difference in proportion [95% CI] 24.7 [7.0, 42.4]), while the number of ventilator days was lower (mean (SD) general 2.1 (4.4), liver 1.1 (3.6), and difference in proportion [95%CI] -0.9 [-2.6, 0.7]). Colloid administration was higher in the liver group (mean (SD) general 23.9 (14.5) ml/kg, liver 48.4 (37.7) ml/kg, and difference in mean [95% CI] 24.6 [12.7, 36.4]), while fresh frozen plasma administration was lower in the liver group (mean (SD) general 15.3 (23.9) ml/kg, liver 6.2 (14) ml/kg, and difference in mean [95% CI] -9.0 [-16.8, -1.3]). There were no significant differences between the groups in postoperative events including blood product transfusions, vasopressor use, and thromboses, or in the intensive care unit and hospital LOS. CONCLUSIONS: The liver group was associated with increased early extubations, decreased ventilator days, and decreased fresh frozen plasma use.

Massive Fetal Transfusion During an Emergency Ex Utero Intrapartum Treatment for a Congenital Infantile Fibrosarcoma: A Case Report.

Although originally described to assist airway management of fetal congenital malformations with life-threatening airway obstruction, the indications for an ex utero intrapartum treatment (EXIT) have expanded to include surgical resection of lesions that are potentially incompatible with life in the absence of uteroplacental circulatory support. We describe the case of an infantile fibrosarcoma (IFS) that presented with fetal hydrops and was successfully managed with an emergency EXIT that necessitated the initiation of a massive fetal blood transfusion both with and without the support of uteroplacental circulation.

Validación de la prueba de Romberg Modificada para la determinación del tiempo de propiocepción inconciente en adultos sanos / Validation of a Modified Romberg's Test to determine normal adult lower limb unconscious proprioception times

Introducción La propiocepción es la capacidad que tiene el cuerpo para detectar el movimiento y la posición articular, lo cual tiene grandes implicaciones en el control neuromuscular. Actualmente no hay una prueba clínica estandarizada que permita determinar objetivamente la normalidad en su evaluación en la población sana con un patrón de marcha maduro. En el año 2012 se diseñó un signo clínico denominado prueba de Romberg modificada, que permite caracterizar los valores propioceptivos de la población normal en los miembros inferiores. Materiales y métodos Estudio de cohorte transversal ciego de 163 pacientes. Se excluyeron pacientes con algún tipo de lesión osteoarticular o neuropatía periférica en los miembros inferiores. Estos individuos se sometieron a la prueba de Romberg modificada, registrando su valor en segundos en el miembro inferior derecho e izquierdo, y comparándolas con la edad, lateralidad y el sexo. Resultados Al estratificar los sujetos evaluados por grupos etarios, se observó una relación inversamente proporcional entre la prueba de Romberg modificada y la edad. La lateralidad y el sexo no presentaron una diferencia significativa (p=0,53).. Discusión La prueba de Romberg modificada, es una prueba útil para la determinación de la propiocepción normal en los adultos, la cual disminuye con la edad sin presentar diferencias con respecto a la lateralidad o el sexo del individuo. Nivel de evidencia IV

Background Proprioception is considered the ability of the body to detect movement and joint position, and has great implications in neuromuscular control. There are currently no standardised clinical tests to objectively determine how much should be considered normal in its evaluation in the healthy population with a mature gait pattern. In 2012, a clinical sign called the modified Romberg test was designed to determine the proprioceptive values in the lower limbs of the normal population. Materials and methods A cross-sectional blind study was conducted on a cohort of patients with no history of osteoarticular injury in the lower limbs and no peripheral neuropathy. The subjects underwent the modified Romberg test, with a record made of its value in seconds in the lower right and left limbs, and comparing them with age, laterality, and gender. Results The study included 163 patients. On stratifying the subjects evaluated according to age groups, a tendency to decrease the modified Romberg test result with increased age was observed. According to the analysis, it can be observed that the proprioception of a limb does not have a significant difference (P=.53) with respect to the contralateral limb (laterality) or gender, but there is with respect to age. Discussion The modified Romberg test result of 20seconds is a useful tool for the determination of normal proprioception in adults. This value decreases with age, without showing differences as regards the laterality or gender of the subject. Evidence Level IV.

Advanced thyroid carcinoma in pregnancy: case report of two pregnancies.

Differentiated thyroid carcinoma is one of the most frequently diagnosed cancers during pregnancy, second only to breast cancer. Therefore, it would be of value to determine if there are pregnancy-related physiological effects that impact long-term prognosis for patients with this disease. Hormone effects attributable to ß-human chorionic gonadotropin and estrogens seem particularly likely. We present a case of a 40-year-old woman with thyroid follicular carcinoma with accompanying bone metastases. The cancer was discovered immediately after childbirth and the woman became pregnant again when the disease was in an advanced stage. We describe the cancer evolution and present the maternal and fetal results. Pregnancy in women with advanced thyroid carcinoma could affect long-term prognosis. However, more studies are needed to evaluate this hypothesis. In this unique case, there were two pregnancies and the second occurred in an advanced state of the disease. We evaluated how these pregnancies could affect short-term prognosis of the disease.

Hiperreactio luteinalis, una causa rara de hipertiroidismo en la gestación / Hyperreactio luteinalis, a rare cause of hyperthyroidism in pregnancy

No disponible

Anti-inflammatory R-prostaglandins from Caribbean Colombian soft coral Plexaura homomalla.

OBJECTIVES: This study aims to evaluate the effect of prostaglandins isolated from soft coral Plexaura homomalla, collected in Colombian Caribbean Sea, on in vivo and in vitro inflammation models. METHODS: Extracts from P. homomalla were fractionated and sequentially chromatographed to obtain the prostaglandins: (15R)-PGA2 (1), (15R)-PGA2 -Me (2), (15R)-O-Ac-PGA2 (3), (15R)-O-Ac-PGA2 -Me (4) and (15R)-PGE2 (5) in addition to three semi-synthetic prostaglandins obtained by transformations of the natural products. The anti-inflammatory properties of natural and semi-synthetic compounds were determined in vivo using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear oedema model and in vitro leucocyte degranulation, myeloperoxidase (MPO) and elastase enzymatic activities from human polymorphonuclear cells (PMNs). The cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. KEY FINDINGS: In the in vivo assay, (15R)-PGE2 (1) and (15R)-O-Ac-PGA2 (3) showed anti-inflammatory activity, as well as in vitro inhibition of elastase release from PMNs. In the PMNs degranulation assay, (15R)-PGE2 (5), was the most active compound in the inhibition of MPO release. Finally, all the tested prostaglandins showed moderate inhibition for elastase enzyme activity, whereas none of the prostaglandins exhibit significative inhibition on MPO activity. CONCLUSION: (15R)-PGE2 (1) and (15R)-O-Ac-PGA2 (3) present significant inhibition on three important events related to the topical inflammatory response induced by TPA: the oedema formation, the PMNs degranulation, events that modulate MPO and elastase levels at inflammation site, and the inhibition of the enzyme activity.

Fuscoside E: a strong anti-inflammatory diterpene from Caribbean octocoral Eunicea fusca.

The screen of 10 soft coral extracts collected from the Colombian Caribbean Sea in the TPA-induced ear edema model allowed us to identify Eunicea fusca extract among others as an interesting source of active compounds. The new diterpene, fuscoside E (1), along with the known fuscoside B (2), fuscol (3), (+)-germacrene D (4) and a mixture of six sterols (5-10), were isolated from this soft coral. Their structures were elucidated by 1D and 2D NMR spectroscopy techniques. Fuscoside E (1) absolute stereochemistry was determined by chiroptical methods. Fuscoside E (1) and B (2) showed strong anti-inflammatory in the above mentioned bioassay. Additionally, fuscoside E (1) and the sterol mixture (5-10) presented antifouling activity against bacterial strains involved in surface colonization.

IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease.

Graft versus host disease (GVHD), mediated by donor T cells, is a significant source of morbidity and mortality following allogeneic stem cell transplantation. Mesenchymal stem cells (MSC) can successfully treat ongoing graft versus host disease, presumably due to their ability to suppress donor T cell proliferation. Little is known about the potential of MSC to prevent GVHD. Here we show that bone marrow-isolated MSC can suppress the development of GVHD if given after donor T cell recognition of antigen. IFN-gamma was required to initiate MSC efficacy. Recipients of IFN-gamma(-/-) T cells did not respond to MSC treatment and succumbed to GVHD. MSC, pre-treated with IFN-gamma, became immediately active and could suppress GVHD more efficiently than a fivefold-greater number of MSC that were not activated. When given at the time of bone marrow transplantation, activated MSC could prevent GVHD mortality (100% survival, p=0.006). MSC activation was dependent on the magnitude of IFN-gamma exposure, with increased IFN-gamma exposure leading to increased MSC suppression of GVHD. Activated MSC present a new strategy for preventing GVHD using fewer MSC.

Mesenchymal stem cells enhance xenochimerism in NK-depleted hosts.

BACKGROUND: Xenogeneic hematopoietic engraftment holds promise as a strategy to achieve whole organ xenograft tolerance. We tested whether xenogeneic bone marrow grafts, engineered with mesenchymal stem cells (MSCs), might provide a new nontoxic approach to enhance xenogeneic engraftment. METHODS: ACI rat MSCs, cultured from whole bone marrow, were identified as CD29+ CD44+OX-18+, CD45-HIS36- and could differentiate into adipogenic and osteogenic tissue. Lethally irradiated B6 mice received ACI whole bone marrow either alone or in combination with ACI MSC. Xenogeneic engraftment was measured in murine peripheral blood on days 7, 50, and 100. Natural killer (NK)-cell-depleted murine recipients treated with or without MSC underwent rat skin graft transplants on the day of the bone marrow infusion. RESULTS: In NK-depleted hosts, control animals failed to survive 60 days; 40% MSC-treated hosts survived >100 days, P < 0 .05. Rat hematopoietic engraftment exceeded 89% on days 7 and 54 and decreased to <25% by day 100. No graft-versus-host disease was observed in MSC-treated animals, P < 0.05. Skin graft survival was prolonged in the MSC-treated group, (21 +/- 1.7 days, P = 0.2). CONCLUSIONS: Our findings present a new approach in engineering xenografts and provide an encouraging platform for additional studies.