Use of Checkpoint Inhibitors in Gray Zone Lymphoma.

Checkpoint inhibitors, cancer immunotherapies, are the new forms of treatment for gray zone lymphoma, a rare subtype that combines the characteristics of both Hodgkin and non-Hodgkin disease forms. Programmed cell death protein 1/programmed cell death ligand 1 (PD-L1/PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) modulate the immune system function. Immunological checkpoints can be stimulatory or inhibitory, and tumors can use these checkpoints to protect against immune system attacks. This is a case report of a difficult diagnosis and describes the most current treatment using checkpoint inhibitors, through the review of the clinical record of a patient diagnosed with gray area lymphoma in August 2019, using a descriptive and cross-sectional analysis of the clinical history and disease evolution. The case showed that pembrolizumab therapy is an effective treatment option for patients with rare gray zone lymphoma refractory to different lines of treatment. Both the diagnosis and treatment of gray area lymphoma remain a challenge for the medical and multiprofessional teams, and collaboration between them ensured effective treatment for the patient.

Three new species of Cyclocephala (Coleoptera: Scarabaeidae: Dynastinae) from Amazonian Peru and a checklist of Cyclocephala species in Peru.

The following new species of Cyclocephala Dejean, 1821 (Coleoptera: Scarabaeidae: Dynastinae: Cyclocephalini) are described from Peru: C. mateoi Paz Ratcliffe, C. ukuku Paz Ratcliffe, and C. hylaea Ratcliffe Paz. A description, diagnosis, geographic distribution, notes on natural history, and illustrations are provided for each new species. Six Cyclocephala species are reported for the first time from Peru: C. emarginata Endrdi, 1964, C. guianae Endrdi, 1969, C. kuntzeniana Hhne, 1923, C. malyi Dupuis, 2014, C. ovulum Bates, 1888, and C. sylviae Dechambre, 1995. An updated, annotated list of the 81 Peruvian species of Cyclocephala is provided.

Clasificación de cesárea según el sistema de Robson en una IPS privada de Cali, 2017 / Cesarean section classification according to Robson's system in a private HSPI in Cali, 2017

RESUMEN Objetivo: Caracterizar las cesáreas según el sistema de clasificación de Robson en una IPS privada de alta complejidad, en el periodo comprendido entre el 1 de enero y el 31 de diciembre de 2017. Métodos: Estudio descriptivo, retrospectivo y de corte transversal realizado en una IPS privada de la ciudad de Cali. Se incluyó en el estudio gestantes ingresadas para atención del parto en el 2017. Se construyó una base de datos en Microsoft Excel 2010, con las variables definidas en la clasificación de Robson y se calculó la tasa de cesáreas, el tamaño relativo de cada grupo y la contribución relativa de cada grupo a la tasa general de cesáreas, así como se analizó las causas de las cesáreas. Se presentan los resultados en tablas. Resultados : La tasa de cesáreas general fue del 35,4 %. Los grupos de mayor contribución al porcentaje total de cesáreas fueron los grupos 2, 1 y 10, con 20,4%, 3,9 % y 3,3 %, respectivamente. El antecedente de cesárea previa fue la causa principal. Conclusiones. Utilizando la clasificación de Robson se logra concluir que es posible reducir la tasa de cesáreas en un 14 % interviniendo el antecedente de cesárea previa.

ABSTRACT Objective : To characterize cesarean sections according to the Robson classification system in a private high complexity HPSI, in the period between January 1 December 31, 2017. Methods : Descriptive, retrospective, cross-sectional study conducted in a private HPSI in the city of Cali. The study included pregnant women admitted for delivery care in 2017. A database was constructed in Microsoft Excel 2010, with the variables defined in Robson's classification. The rate of cesarean sections, the relative size of each group and the relative contribution of each group to the overall rate of cesarean sections were calculated, as well as the causes of cesarean sections were analyzed. The results are presented in tables. Results : The overall cesarean section rate was 35.4 %. The groups with the highest contribution to the total percentage of cesarean sections were groups 2, 1 and 10 with 20.4 %, 3.9 % and 3.3 %, respectively. History of previous cesarean section was the main cause. Conclusions: Using Robson's classification, it can be concluded that it is possible to reduce the rate of cesarean section rate by 14 % by intervening in the history of previous cesarean section.

El género Eurysternus Damlan, 1824 (Coleoptera: Scarabaeidae: Oniticellini) del departamento de Loreto, Perú / The genus Eurysternus Dalman, 1824 (Coleoptera: Scarabaeidae: Oniticellini) from Loreto department, Peru

Resumen Presentamos 13 especies del género Eurysternus (Coleoptera: Scarabaeidae: Oniticellini) del departamento de Loreto - Perú. Registramos por primera vez para Perú a la especie Eurysternus ventricosus Gill, 1990. Además, proporcionamos fotos de los habitus y aedeagus y mapas de distribución de las especies encontradas en este departamento.

Abstract Thirteen species of the genus Eurysternus (Coleoptera: Scarabaeidae: Oniticellini) occurring in Loreto Department - Peru are presented. Eurysternus ventricosus Gill, 1990 is recorded for the first time in Peru. Additionally, the habitus and aedeagus are illustrated, and distribution records for all the species found in the department are presented.

Laparoscopic Sleeve Gastrectomy for High-Risk Patients in a Monocentric Series: Long-Term Outcomes and Predictors of Success.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has gained popularity as a stand-alone bariatric procedure, but only a few reports provide data of long-term outcomes on high-risk patients. OBJECTIVE: To evaluate long-term efficacy of LSG as a definitive management on high-risk obese patients and to study factors that predict its success. SETTING: University hospital in Spain. METHODS: A retrospective analysis of prospectively collected data from 134 high-risk patients undergoing LSG from January 2007 through December 2016. Long-term weight loss, resolution of comorbidities, morbidity, and mortality were analyzed. RESULTS: One hundred thirty-four high-risk patients underwent LSG. The mean overall follow-up time was 70.9 ± 4.5 months. The mean age was 47 ± 11.0 years. The mean preoperative body mass index (BMI) was 55.9 ± 6.7 kg/m2 (83.5% were super-obese and 24.6% had BMI ≥ 60). The incidence of postoperative complications was 15%. Mean percentage of total weight loss (%TWL) at 5, 6, 7, and 8 years was 30.7 ± 12.8%, 28.7 ± 14.0%, 29.7 ± 12.3%, and 27.9 ± 11.1%, respectively. Differences were found in age, preoperative BMI, time to reach nadir weight and percentage of excess weight loss (%EWL) at 1 year between patients considered a failure compared to those considered a success. Using multivariate regression analysis, only age (p = 0.009) and time to reach nadir weight after surgery (p = 0.008) correlated with %EWL at 4 years. Resolution of type 2 diabetes (T2DM) was achieved in 62.2% of patients. CONCLUSION: This study supports effectiveness and durability of LSG as a definitive bariatric procedure in high-risk patients.

Endometriosis de localización extraovárica. Nuestra casuística en 10 años / Extraovarian endometriosis. Our 10-year casuistics

Introducción. La endometriosis es una enfermedad ginecológica cuya prevalencia oscila alrededor del 5-10% de las mujeres. La localización es pélvica en la mayoría de los casos; sin embargo, en un pequeño grupo de pacientes, puede presentarse en regiones diferentes de esta. Material y métodos. Estudio descriptivo, observacional y retrospectivo de las historias clínicas de 26 pacientes intervenidas quirúrgicamente de endometriosis de localización extraovárica en el Hospital General Universitario de Ciudad Real en el período comprendido entre enero del 2003 y enero del 2013. Resultados. Nuestra serie consta de 26 pacientes intervenidas de endometriosis de localización extraovárica. Las localizaciones, por orden de frecuencia, fueron: pared abdominal, ombligo, vulva, apéndice, íleon, saco herniario y colon. Discusión. La localización extrapélvica de la endometriosis se presenta con muy baja frecuencia. El tratamiento quirúrgico es la elección, llevando a cabo una resección con márgenes suficientes que permitirá reducir las posibilidades de recidiva (AU)

Introduction. Endometriosis is a gynecological disease with a prevalence of about 5% to 10% of women. Localization is usually pelvic but in a small group of patients the disease can be localized elsewhere. Material and methods. We performed a descriptive, observational and retrospective study of the medical records of 26 patients treated surgically for extraovarian endometriosis at the University General Hospital of Ciudad Real between January 2003 and January 2013. Results. Our series included 26 patients who underwent surgery for extraovarian endometriosis. In order of frequency, the locations were the abdominal wall, umbilicus, vulva, appendix, ileum, hernia sac and colon. Discussion. The frequency of extrapelvic endometriosis is very low. The treatment of choice is surgery. Resection with adequate margins reduces the chances of recurrence (AU)

Determinación rápida intraoperatoria de la paratirina intacta en la cirugía del hiperparatiroidismo primario. La experiencia en nuestro centro / Rapid intraoperative determination of intact parathyroid hormone during surgery for primary hyperparathyroidism. Experience at our center

INTRODUCCIÓN: El hiperparatiroidismo primario (HPTP) se debe a un adenoma único en el 85-95% de las ocasiones, lográndose frecuentemente la curación con la extirpación del mismo. La determinación rápida intraoperatoria de la paratirina intacta (PTHio) puede constituir una herramienta para el control de la efectividad de la cirugía del HPTP. El objetivo principal de nuestro estudio fue evaluar la determinación de PTHio y objetivar si su implementación colaboraba en lograr la aplicación de una cirugía mínimamente invasiva (CMI) y en régimen de cirugía mayor ambulatoria (CMA) en el tratamiento del HPTP. MATERIAL Y MÉTODOS: Estudio retrospectivo de una serie consecutiva de pacientes diagnosticados e intervenidos quirúrgicamente de HPTP en el Hospital General Universitario de Ciudad Real entre enero de 2005 y enero de 2012. RESULTADOS: En el periodo estudiado, se intervinieron 91 pacientes. 39 (42,9%) fueron intervenidos bajo anestesia general y 52 (57,1%) fueron candidatos a anestesia locorregional mediante bloqueo cervical. Del total, 76 (83,5%) fueron subsidiarios de CMI con abordaje unilateral. En el resto se realizó cervicotomía clásica. En 75 pacientes se realizó la determinación de PTHio, de los cuales, en 68 se demostró curación en el mismo acto quirúrgico. El 70,3% (64) de los pacientes fueron intervenidos en régimen de CMA. CONCLUSIONES: La determinación de PTHio puede permitir modificar la estrategia quirúrgica del HPTP en nuestro servicio, colaborando en la realización de una CMI en un porcentaje importante de pacientes, de forma ambulatoria, con alguna mejora estética, probablemente menor dolor, menor ingreso y con menos complicaciones potenciales que en la exploración cervical bilateral

INTRODUCTION: Primary hyperparathyroidism (PHPT) is due to a single adenoma in 85%-95% of cases, and is often cured after adenoma removal. Intraoperative rapid determination of intact parathyroid hormone (PTHio) may be a tool for monitoring the effectiveness of PHPT surgery. The main objective of our study was to evaluate PTHio determination and to establish whether its successful implementation contributed to achieve minimally invasive surgery (MIS) and major ambulatory surgery (MAS) in the treatment of PHPT. MATERIAL AND METHODS: Retrospective study of a consecutive series of patients diagnosed and operated on for PHPT at the University General Hospital of Ciudad Real between January 2005 and January 2012.RESULTS: In the study period, 91 patients underwent surgery. 39 (42.9%) under general anesthesia, while 52 (57.1%) were candidates for regional anesthesia by cervical block. Seventy-six of all patients (83.5%) were amenable to MIS using a unilateral approach. Classical cervicotomy was performed in all other patients. PTHio determination was done in 75 patients, showing cure in the same surgery in 68 of them. MAS was performed in 70.3% (64) of patients. CONCLUSIONS: Determination of PTHio may allow for changing the surgical approach to PHPT at our department, allowing for performance of MIS on an outpatient basis in a significant proportion of patients with some cosmetic improvement, probably less pain, shorter hospital stay, and less potential complications than bilateral cervical exploration

Rapid intraoperative determination of intact parathyroid hormone during surgery for primary hyperparathyroidism. Experience at our center.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is due to a single adenoma in 85%-95% of cases, and is often cured after adenoma removal. Intraoperative rapid determination of intact parathyroid hormone (PTHio) may be a tool for monitoring the effectiveness of PHPT surgery. The main objective of our study was to evaluate PTHio determination and to establish whether its successful implementation contributed to achieve minimally invasive surgery (MIS) and major ambulatory surgery (MAS) in the treatment of PHPT. MATERIAL AND METHODS: Retrospective study of a consecutive series of patients diagnosed and operated on for PHPT at the University General Hospital of Ciudad Real between January 2005 and January 2012. RESULTS: In the study period, 91 patients underwent surgery. 39 (42.9%) under general anesthesia, while 52 (57.1%) were candidates for regional anesthesia by cervical block. Seventy-six of all patients (83.5%) were amenable to MIS using a unilateral approach. Classical cervicotomy was performed in all other patients. PTHio determination was done in 75 patients, showing cure in the same surgery in 68 of them. MAS was performed in 70.3% (64) of patients. CONCLUSIONS: Determination of PTHio may allow for changing the surgical approach to PHPT at our department, allowing for performance of MIS on an outpatient basis in a significant proportion of patients with some cosmetic improvement, probably less pain, shorter hospital stay, and less potential complications than bilateral cervical exploration.

Angiosarcoma primario de mama y carcinoma papilar de tiroides sincrónico: presentación de un caso / Primary breast angiosarcoma and synchronous papillary carcinoma of thyroid: a case report

Presentamos el caso excepcional de paciente con angiosarcoma primario de mama y carcinoma papilar de tiroides sincrónicos. Mujer de 34 años con angiosarcoma primario en la mama derecha sometida a mastectomía simple. En el estudio de extensión se halló un incidentaloma tiroideo derecho compatible con carcinoma papilar que requirió tiroidectomía total y linfadenectomía del compartimento central en segundo tiempo. Los angiosarcomas primarios suponen menos del 0,05% de todos los tumores primarios malignos de la mama. El diagnóstico definitivo de estos tumores viene definido por el estudio anatomopatológico, que define tres grados: alto, bajo, intermedio, los cuales se relacionan de forma directa con la supervivencia. La prevalencia de los incidentalomas malignos tiroideos objetivados por PET varía del 14% - 30,9%. La planificación del tratamiento quirúrgico de las neoplasias incidentales tiroideas en pacientes con otro tumor primario debe analizarse de forma individualizada, según la supervivencia esperada del tumor primario

Present the exceptional case of a female patient with diagnostic of primary angiosarcoma of the breast and synchronous thyroid papillary carcinoma, we review the literature. Patient female 34 year old with diagnostic of primary angiosarcoma in the right breast, it was removed,in the extension study found an incidental thyroid papillary carcinoma that required total thyroidectomy and central lymphadenectomy in a second time. The primary angiosarcomas account for less than 0.05% of all primary malignant tumors of the breast. The definitive diagnosis is determined by the pathology study, which defines three grades: high, low and intermediate, which relate directlyto the survival. The prevalence of malignant thyroid incidentalomas was observed by PET varies from 14% to30,9%, according to different studies. Planning the surgical treatment of incidental thyroid malignancies in patients with other primary tumor should be analyzed individually,according the expected survival of the primary tumor

Estudio clínico y molecular de cinco familias con resistencia a la acción de las hormonas tiroideas / Clinical and molecular study of five families with resistance to thyroid hormones

Fundamento y objetivo: La resistencia a la acción de las hormonas tiroideas (SRHT) es un síndrome causado mayoritariamente por mutaciones en el gen receptor beta de las hormonas tiroideas (THRB). Se estudian cinco familias con fenotipo de SRHT. Pacientes y método: Se realizó secuenciación de THRB. Se evaluó la respuesta a triyodotironina (T3) y efecto dominante negativo de los mutantes in vitro y se estudiaron los mecanismos de resistencia en sujetos sin mutación THRB cuantificando en cultivos de fibroblastos cambios de expresión en los genes regulator of calcineurin 2 (ZAKI4) y Kruppel-like factor 9 (BTEB). Resultados: Tres casos presentaron mutaciones en THRB: R243Q, R320C, R429Q, dando lugar a receptores TRβ con menor respuesta a T3. R243Q y R320C ejercen efecto dominante negativo. Un sujeto sin mutación THRB presentó cambios de expresión en ZAKI4 y BTEB similar a R230C, mientras que el otro mostró niveles de expresión superiores a los controles. Conclusiones: Mutaciones heterocigotas en THRB causaron tres de los casos de SRHT estudiados. Uno de los casos con SRHT sin mutación se comporta a nivel molecular como los portadores de mutación, mientras que en el otro la resistencia no está mediada por TRβ (AU)

Background and objective: Resistance to thyroid hormone (RTH) is a syndrome mostly caused by mutations in thyroid hormone receptor beta gen (THRB). We present five families with RTH phenotype. Patients and methods:THRB gene sequencing. In vitro studies to evaluate the mutants response to thyroid hormones and their dominant negative effect. Mechanism of resistance in patients with RTH without THRB mutations quantifying expression of regulator of calcineurin 2 (ZAKI4) and Kruppel-like factor 9 (BTEB) genes in patients fibroblast cultures.Results: THRB mutations were found in three cases: R243Q, R320C, R429Q. Mutants showed a decreased response to T3. R243Q and R320C had a strong dominant negative effect. One subject without THRB mutation showed changes in ZAKI4 and BTEB expression similar to R320C and the other showed expression levels higher than normal controls. Conclusions:Three cases of RTH were caused by THRB heterozygous mutations but in two cases mutations were not found. THRB mutation carriers and one of the patients without mutations share a similar mechanism of resistance and in the other subject RTH is TRβ independent (AU)

[Clinical and molecular study of five families with resistance to thyroid hormones]. / Estudio clínico y molecular de cinco familias con resistencia a la acción de las hormonas tiroideas.

BACKGROUND AND OBJECTIVE: Resistance to thyroid hormone (RTH) is a syndrome mostly caused by mutations in thyroid hormone receptor beta gen (THRB). We present five families with RTH phenotype. PATIENTS AND METHODS: THRB gene sequencing. In vitro studies to evaluate the mutants response to thyroid hormones and their dominant negative effect. Mechanism of resistance in patients with RTH without THRB mutations quantifying expression of regulator of calcineurin 2 (ZAKI4) and Kruppel-like factor 9 (BTEB) genes in patients fibroblast cultures. RESULTS: THRB mutations were found in three cases: R243Q, R320C, R429Q. Mutants showed a decreased response to T3. R243Q and R320C had a strong dominant negative effect. One subject without THRB mutation showed changes in ZAKI4 and BTEB expression similar to R320C and the other showed expression levels higher than normal controls. CONCLUSIONS: Three cases of RTH were caused by THRB heterozygous mutations but in two cases mutations were not found. THRB mutation carriers and one of the patients without mutations share a similar mechanism of resistance and in the other subject RTH is TRß independent.

A family with congenital hypothyroidism caused by a combination of loss-of-function mutations in the thyrotropin receptor and adenylate cyclase-stimulating G alpha-protein subunit genes.

BACKGROUND: Resistance to thyrotropin (TSH) causes congenital hypothyroidism (CH). TSH receptor (TSHR) and adenylate cyclase-stimulating G alpha protein subunit (GNAS) loss-of-function mutations cause TSH resistance. We describe a family with TSH resistance and CH bearing a combination of inactivating mutations in TSHR and GNAS genes. We describe studies to determine the molecular mechanisms involved in TSH resistance in this family. METHODS: DNA sequencing to identify TSHR and GNAS gene mutations was performed. In vitro effects of the mutations on cAMP production and TSH binding were investigated in COS7 cells. cAMP production was evaluated by transfecting a cAMP response element (CRE)-luciferase reporter with pSVL-TSHR and pSVK3-GNAS vectors. For binding studies, cells transfected with pSVL-TSHR vectors were incubated with iodine-125 bovine TSH ((125)IbTSH). RESULTS: Family members with and without CH were heterozygous for the TSHR mutant p.E34K or the GNAS mutant c.750_751insA (=GNASMut). The propositus had CH and he was heterozygous for TSHR p.E34K; his mother, also heterozygous for TSHR p.E34K, did not have CH. The euthyroid propositus' wife was heterozygous for GNASMut. The propositus' two daughters had CH, one was heterozygous for GNASMut and the other a compound heterezygous for TSHR p.E34K and GNASMut. Albright's hereditary osteodystrophy phenotype was present in those with GNASMut mutation but only the daughters had pseudohypoparathyroidism type 1a. Cells transfected with TSHRE34K had lower TSH affinity and less CRE-luciferase response than cells transfected with TSHR wild-type (WT). Cells transfected with GNASMut did not stimulate CRE-luciferase activity, but when cells were transfected with GNASMut plus GNASWT, a similar response to GNASWT alone was observed. The combination of TSHRWT and GNASWT showed higher CRE-luciferase response than TSHRWT and TSHRE34K with either GNASWT or GNASWT plus GNASMut. CONCLUSIONS: CH was caused by loss-of-function mutations in TSHR and/or GNAS. The absence of CH in the propositus' mother argues against a role for TSHR p.E34K being the only cause of CH. The minimal thyroidal phenotypic differences between the sisters with pseudohypoparathyroidism type 1a and TSH resistance, both heterozygous for GNAS c.750_751insA but only one bearing the TSHR p.E34K mutant, suggest that the main cause for CH was preferential expression of the mutated maternal GNAS allele in the thyroid gland.

Colecistectomía laparoscópica de puerto único en un programa de CMA / Single port laparoscopic cholecystectomy in major ambulatory surgery (MAS)

Introducción: La cirugía endoscópica por orificios naturales es una nueva modalidad quirúrgica en fase de desarrollo. La vía más natural para los cirujanos es usar una cicatriz ya existente como es el ombligo. La reciente introducción de trocares diseñados para este fin ha hecho posible su puesta en práctica. Material y métodos: En este estudio presentamos nuestra experiencia preliminar en la colecistectomía laparoscópica con puerto de acceso único umbilical, mediante un estudio prospectivo que incluye a 26 pacientes intervenidos entre enero 2009 y enero 2010. También pretendemos conocer su posible realización en régimen de CMA. Resultados: Todos los pacientes presentaban colelitiasis no complicadas, aunque en 5 se identifico una colecistitis en la cirugía. El tiempo quirúrgico promedio fue de 51,2min. La estancia hospitalaria media fue 25,7h. En el 76,92% de los pacientes el ingreso fue menor de 24h. No hubo ningún reingreso ni complicación intraoperatoria o postoperatoria importante. Conclusiones: A la vista de nuestros resultados la colecistectomía laparoscópica por puerto único favorece su inclusión en un programa de cirugía mayor ambulatoria (AU)

Introduction: Natural orifice endoscopic surgery is a new surgical procedure still in the development phase. The most natural entry for surgeons is to use an already existing scar, such as the navel. The recent introduction of trocars designed for this purpose has made it possible to put this into practice. Material and methods: We present our preliminary experience in single trans‐umbilical incision laparoscopic cholecystectomy, by means of a prospective study which included 26 patients operated on between January 2009 and January 2010. We also attempt to find out whether it can be performed in a MAS programme. Results: All patients had uncomplicated cholelithiasis, although in 5 of them cholecystitis was identified during the surgery. The mean surgical time was 51.2min. The mean hospital stay was 25.7h, and 76.92% of patients were admitted for less than 24h. There were no re-admissions or significant intra-operative or post-operative complications. Conclusions: On looking at our results, single port laparoscopic cholecystectomy could be included in a major ambulatory surgery programme (AU)

[Single port laparoscopic cholecystectomy in major ambulatory surgery (MAS)]. / Colecistectomía laparoscópica de puerto único en un programa de CMA.

INTRODUCTION: Natural orifice endoscopic surgery is a new surgical procedure still in the development phase. The most natural entry for surgeons is to use an already existing scar, such as the navel. The recent introduction of trocars designed for this purpose has made it possible to put this into practice. MATERIAL AND METHODS: We present our preliminary experience in single trans-umbilical incision laparoscopic cholecystectomy, by means of a prospective study which included 26 patients operated on between January 2009 and January 2010. We also attempt to find out whether it can be performed in a MAS programme. RESULTS: All patients had uncomplicated cholelithiasis, although in 5 of them cholecystitis was identified during the surgery. The mean surgical time was 51.2 min. The mean hospital stay was 25.7h, and 76.92% of patients were admitted for less than 24h. There were no re-admissions or significant intra-operative or post-operative complications. CONCLUSIONS: On looking at our results, single port laparoscopic cholecystectomy could be included in a major ambulatory surgery programme.

A novel phenotypic expression associated with a new mutation in LMNA gene, characterized by partial lipodystrophy, insulin resistance, aortic stenosis and hypertrophic cardiomyopathy.

BACKGROUND: Lipodystrophies are a heterogeneous group of diseases characterized by abnormal fat distribution. Familial partial lipodystrophy 2 (FPLD2) is due to mutations in the LMNA gene. Previous studies have suggested that LMNA mutations 5' to the nuclear localization signal (NLS) are more likely to underlie laminopathies with cardiac or skeletal muscle involvement, while mutations 3' to the NLS are more likely to underlie lipodystrophy and progeroid syndromes. OBJECTIVE: To study the clinical and molecular features of a subject with FPLD. SUBJECTS AND METHODS: We carried out mutational analysis of LMNA gene in a woman with FPLD phenotype and in her relatives. Insulin resistance was evaluated by minimal model. Body composition was evaluated by dual-energy X-ray absorptiometry (DEXA). Echocardiography was done in affected subjects. 3T3-L1 preadipocytes were transfected with wild-type or mutant prelamin A constructs. In transfected cells, lamin A was detected using a Cy3-conjugated monoclonal anti-FLAG antibody. RESULTS: The patient showed atypical fat distribution, insulin resistance, severe aortic stenosis and hypertrophic cardiomyopathy. She has an affected 11-year-old son, not yet lipodystrophic but with an incipient aortic disease. LMNA sequencing showed that mother and son were both heterozygous for a novel c.1772G > T missense mutation in exon 11, which causes the substitution of the cysteine at residue 591 by a phenylalanine (C591F). In mouse preadipocytes transfected with the mutant human LMNA gene, the mutant lamin A isoform was mislocated in the nucleus. CONCLUSIONS: This patient shows a novel clinical form of FPLD2, due to a mutation affecting lamin A only, with cardiac involvement.

Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock.

OBJECTIVE: Septic shock is one of various causes of nonthyroidal illness syndrome (NTIS). In humans, the molecular mechanisms involved in NTIS are mostly unknown. The aim of this study was to investigate, in patients with NTIS secondary to septic shock, changes in the expression of genes involved in the actions of thyroid hormones and in the activity of deiodinase enzymes, in two tissues important for protein and energy metabolism, skeletal muscle (SM) and subcutaneous adipose tissue (SAT). DESIGN: Hospitalized patients were divided into a control and a septic shock NTIS group. MEASUREMENT: Serum collection for biochemical measurements, and SM and SAT biopsies for mRNA expression analysis of thyroid hormone receptors (THRB1, THRA1), retinoid X receptors (RXRA, RXRB, RXRG), nuclear receptor corepressor (NCOR1), silencing mediator of retinoid and thyroid hormone receptor (SMRT), steroid receptor coactivator (SRC1), type 1 and 2 deiodinases (D1, D2), monocarboxylate transporter 8 (MCT8), SECIS binding protein 2 (SBP2) and uncoupling protein 3 (UCP3) as well as D1, D2 and D3 enzyme activity measurements. RESULTS: The NTIS group had lower serum TSH, and free T3 and higher rT3 than controls. D1 and D3 were detected in SAT, with no differences found between the two groups; SM had very low D2 activity and again no differences were found between groups; D3 activity in SM was higher in NTIS than controls. SM expression of THRB1, RXRG and D2 was lower and RXRA higher in NTIS than controls. SAT from NTIS patients had lower MCT8, THRB1, THRA1, RXRG and SMRT, and higher UCP3 expression than controls. CONCLUSIONS: In patients with septic shock NTIS tissue responses are orientated to decrease production and increase degradation (muscle) or decrease uptake (adipose tissue) of T3, as well as to decrease thyroid hormone actions.

Cuidados de niños con traqueostomía / Care of the child with tracheostomy

Existe un número creciente de niños con vía aérea artificial, que han debido ser traqueostomizados por necesidad de recibir ventilación mecánica prolongada o por causas congénitas y adquiridas de obstrucción de la vía aérea superior. Aproximadamente un 40 por ciento de los pacientes tienen requerimientos tecnológicos especiales que limitan aún más su posibilidad de manejo ambulatorio. El presente documento aborda los principales cuidados necesarios de observar para facilitar los manejos domiciliarios entregados por la familia, sus cuidadores inmediatos y el equipo de salud.