Low-Dose Aspirin Use Does Not Increase Disease Activity in Pregnant Patients with Inflammatory Bowel Disease.

BACKGROUND: The adverse effects of non-steroidal anti-inflammatory (NSAID) drugs on the gastrointestinal system are well recognized, but the effect of NSAID use on disease activity patients with inflammatory bowel disease (IBD) remains unresolved. Low-dose aspirin (LDA) is recommended for all pregnant patients with risk factors for developing preeclampsia, including autoimmune conditions. As recognition of risk factors for preeclampsia improves, the preventative use of LDA is likely to increase. AIMS: To investigate if LDA use for prevention of preeclampsia increases the risk of disease activity in pregnant women with IBD. METHODS: Single-center retrospective cohort study of pregnant patients with IBD who delivered from 2012 to 2020, comparing those with and without LDA use. Primary outcome was odds of clinical IBD activity in patients in remission at time of conception. Secondary outcomes were rate of elevated inflammatory biomarkers, defined as C-reactive protein > 5 ug/mL or fecal calprotectin > 250 ug/g, and rate of preeclampsia. Univariate analyses tested for associations. RESULTS: Patients taking LDA were older (p = 0.003) and more likely to have chronic hypertension (p = 0.002), to have undergone in vitro fertilization (p < 0.001), and to be on biologics (p = 0.03). Among patients in remission at conception, there was no difference in clinical disease activity or biomarker elevation during pregnancy based on LDA use (OR 1.27, 95% CI [0.55-2.94], p = 0.6). Rates of preeclampsia were similar between groups. CONCLUSION: LDA use for preeclampsia prevention did not increase the incidence of disease activity in pregnant patients with IBD.

Peripartum Exposure to Biologic Therapy Does Not Impact Postpartum Wound Healing in Women With IBD.

BACKGROUND: Inflammatory bowel disease (IBD) commonly affects women during childbearing years and often requires antepartum therapy. Data regarding effects of biologic exposure on delivery outcomes are limited. We explored whether peripartum biologic exposure impacts wound healing following cesarean section (C-section) and vaginal delivery (VD) in IBD patients. METHODS: Pregnancy and IBD data from the IBD Preconception and Pregnancy Planning (I-PrePP) Clinic database were collected and analyzed. Primary outcome was frequency of postpartum wound infection in women receiving peripartum biologics, defined as exposure in the third trimester and up to 2 weeks postdelivery relative to nonexposed patients. Secondary outcomes included effect of peripartum biologic timing and IBD phenotype on wound healing. Descriptive statistics summarized data using frequency for categorical variables and median for continuous variables. Univariate analyses tested associations when appropriate. RESULTS: Of 100 deliveries (interquartile range, 30-35; median, 33 years old), 58 were C-sections and 42 VDs. Peripartum biologic exposure occurred in 72% (42 of 58) and 57% (24 of 42), respectively. Median time from last dose to delivery was 6 (interquartile range, 4-8) weeks; 21 (32%) received biologics within 72 hours following delivery. Seven infections occurred following C-section among 5 unique CD patients. Peripartum biologic exposure was not associated with infection (4 of 66 [6%] exposed vs 3 of 34 [8.8%] nonexposed; P = .68), nor was disease activity (P = 1.0). Crohn's disease (P = 0.02), internal penetrating phenotype (P < .001), prior IBD surgery (P = .03), and prior postpartum infection (P = .04) were associated with infection. CONCLUSIONS: Peripartum biologic exposure does not impair postpartum wound healing; however, patients with more complicated disease phenotypes require close monitoring.

No prior studies have explored risk of postpartum wound infection in women receiving biologics in the peripartum period. We found no significant increase in risk of postpartum wound infection; however, internal penetrating Crohn's phenotype may be an important risk factor.

Exposure to biologic therapy and associated maternal and neonatal outcomes in pregnancies complicated by inflammatory bowel disease.

BACKGROUND: There is growing evidence that biologic therapy is safe in pregnancies complicated by inflammatory bowel disease and that its use outweighs the risk of worsening disease activity, which is associated with adverse pregnancy outcomes. To our knowledge, there are limited data regarding the use of biologic therapy and the associated maternal adverse effects such as the risk of hypertensive outcomes, postoperative complications, and infectious risk. OBJECTIVE: Our objective was to evaluate a variety of obstetrical complications including maternal infectious outcomes, hypertensive outcomes, other adverse maternal outcomes including postoperative complications, venous thromboembolism, and postpartum hemorrhage; we also evaluated the neonatal outcomes associated with biologic use in pregnancies affected by inflammatory bowel disease. STUDY DESIGN: This was a retrospective cohort study including patients with inflammatory bowel disease who were pregnant and delivered at our institution. The maternal demographics and the incidence of maternal and neonatal outcomes were compared among groups on the basis of biologic exposure using the chi-square or Fisher exact test for categorical variables and the t test or Mann-Whitney test for continuous variables. Multivariable logistic regression analysis was performed on composite outcomes adjusting for age, disease activity, maternal obesity, history of cesarean delivery, and history of corticosteroid use in pregnancy. The statistical significance was defined as P<.05. RESULTS: A total of 322 patients who were pregnant, had inflammatory bowel disease, and delivered at our institution from 2012 to 2019, were included for analysis. Of these, 112 (34%) were on biologics during pregnancy. The patients in the biologic group had significantly lower body mass indices than the patients in the nonbiologic group (median body mass index, 22.4 vs 24.0, respectively; P=.04), and they were less likely to be multiparous (41% vs 59%, respectively; P=.003). In addition, more patients in the biologic group were likely to have Crohn disease with previous inflammatory bowel disease surgery (33% vs 20%, respectively; P=.01); otherwise, the 2 groups had similar baseline characteristics. Maternal infectious and hypertensive outcomes occurred significantly more frequently in the biologic group than the nonexposed group (22% vs 7%; P=.0003 and 19% vs 8%; P=.003, respectively). This remained statistically significant in multivariable logistic regression models. Specifically, maternal infectious and hypertensive outcomes occurred significantly more frequently in the patients on a single-agent antitumor necrosis factor treatment than the patients on no inflammatory bowel disease medication (24% vs 6%; P=.002; 22% vs 6%; P=.004), which remained statistically significant in multivariable logistic regression models. There was no difference in the neonatal adverse outcomes between the 2 groups. CONCLUSION: Our data suggest an association between antepartum biologic use- specifically antitumor necrosis factor alpha therapy-and an increased risk of maternal infectious and hypertensive outcomes. This increased risk may be related to underlying disease activity and the same should be incorporated into a discussion with the patient. However, the discussion must be balanced with the important benefit of optimal disease control associated with biologic use in patients being treated for IBD.

Accuracy of third trimester ultrasound in predicting neonatal birthweight in patients with inflammatory bowel disease.

OBJECTIVE: To evaluate the accuracy of third trimester ultrasound in predicting birthweight in patients with inflammatory bowel disease (IBD) using the gestation-adjusted projection (GAP) method. STUDY DESIGN: Retrospective cohort study including pregnant patients with IBD who had third trimester ultrasounds and delivered at a single institution from 2012 to 2017. Controls included pregnant patients without IBD seen during the study period with third trimester ultrasounds. Correlation plots of GAP birthweight and actual birthweight (AB) were created for IBD-positive cases, IBD-negative controls, and IBD-positive cases with and without prior abdominal surgery. GAP predicted birthweight error was calculated for cases and controls. Univariable linear regression models estimated the association between predicted birthweight and AB. Multivariable linear regression models estimated the association between GAP birthweight and AB adjusting for age, BMI, race, and IBD status. RESULTS: 320 patients were included (172 cases and 148 controls). Cases were more likely to be older (p < 0.001), white (p < 0.001), and have a lower BMI (p = 0.001). Correlation plots of GAP birthweight and AB showed linear correlations in cases (Spearman ρ = 0.81), controls (ρ = 0.74), cases with (p = 0.78) and without prior surgery (ρ = 0.83). GAP birthweight was significantly associated with AB in controls and cases in univariable linear regression models (ß = 0.85, standard error = 0.04, p < 0.001; ß = 0.90, standard error = 0.06, p < 0.001, respectively). No significant difference was found between the parameter estimates of the two models (p = 0.47). GAP birthweight remained significantly associated with AB in a multivariable linear regression model (ß = 0.86, standard error = 0.03, p < 0.001). There were no significant differences between GAP predicted birthweight error between controls and cases (APE 11% vs 10% respectively, p = 0.56) and between cases without and with prior surgery (APE 10% vs 11%, p = 0.7). CONCLUSION: The accuracy of fetal biometry in the third trimester for predicting actual birthweight was equivalent between patients with and without IBD and those with prior abdominal surgery.

Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies.

BACKGROUND & AIMS: The effect of pregnancy on inflammatory bowel disease (IBD) remains poorly understood. We aimed to monitor intestinal inflammation using fecal calprotectin (FC) in pregnant women and their babies during early life. METHODS: Pregnant women with or without IBD and their infants were prospectively enrolled. FC levels were measured at each trimester of pregnancy and in babies throughout the first 3 years of life. Repeated-measures analysis was applied to investigate changes in FC levels while adjusting for confounders. The FC levels were correlated with the bacterial abundance in both mothers and babies. RESULTS: Six hundred and fourteen fecal samples from 358 mothers (98 with IBD) and 1005 fecal samples from 289 infants (76 born to IBD mothers) were analyzed. Pregnant Patients with IBD maintained higher FC levels through pregnancy compared with controls (P = 7.5 × 10-54). FC gradually increased in controls and declined in Patients with IBD throughout pregnancy (P for interaction = 5.8 × 10-7). Babies born to mothers with IBD presented with significantly higher FC levels than those born to controls up to 3 years of age, after adjusting for sex, delivery mode, feeding behavior, and antibiotics exposure (2 weeks to 3 months of age, P = .015; 12-36 months of age, P = .00003). Subdoligranulum, Roseburia, Fusicatenibacter, and Alistipes negatively correlated, and Streptococcus, Prevotella, Escherichia-Shigella, and Bifidobacterium positively correlated with maternal FC levels at T3. Faecalibacterium, Bifidobacterium, and Alistipes showed negative correlations, and Streptococcus were positively correlated with FC levels within 3 months of birth. CONCLUSIONS: Pregnancy is associated with decreased inflammatory activity in mothers with IBD. Higher FC levels in babies born to mothers with IBD suggest subclinical inflammation in early life, the long-term consequences of which are uncertain.

Identifying Patient Priorities for Preconception and Pregnancy Counseling in IBD.

BACKGROUND: Inflammatory bowel disease (IBD) commonly affects women of reproductive age. Many patients lacking knowledge about IBD and reproduction make uninformed decisions, such as voluntary childlessness and medication cessation. Education should be individualized to the patient's knowledge base and include topics of most importance to the patient. Our study aimed to describe the priority rankings of topics selected by patients seeking preconception and pregnancy counseling. METHODS: As part of an ongoing prospective study, patients with IBD were asked to rank, in order of importance, nine a priori preconception, pregnancy, and postpartum topics they would like addressed by our specialized care team, which includes an IBD physician and a high-risk obstetrician. χ2 and Fisher's exact tests were used to assess associations between clinical and demographic characteristics and priority rankings, and a p value cutoff for significance was set as .05. RESULTS: One hundred and fifty-eight women with IBD (mean (IQR) age; 32 (28-37) years) were seen in consultation, and 116 (70 (60%) CD, 43 (37%) UC, and 3 (3%) IBD-U) completed intake forms were analyzed. There were 78 (68%) women seen in the preconception stage, median age 31 (IQR 28-34), and 38 women (32%) were pregnant, median age 32 (IQR 28-33). Safety of IBD medications during pregnancy was most commonly ranked as top priority (40%) for all patients regardless of pregnancy status, followed by control of IBD disease activity and impact on pregnancy (31%), impact of IBD and surgery on fertility (19%), pregnancy outcomes for the baby (18%), mode of delivery (6%), inheritance of IBD (4%), breastfeeding (2%), nutritional health (2%), and vaccines and newborn care (1%). The impact of IBD and surgery on fertility was ranked as the number one priority more often in the preconception group (p value < 0.01) and mode of delivery in the pregnancy group (p value 0.04). CONCLUSION: Safety of IBD medications remains a priority topic for patients seeking preconception and pregnancy counseling.

Placental cord insertion distance from the placental margin and its association with adverse perinatal outcomes.

OBJECTIVE: The placental cord insertion (PCI) to the placental margin has not been well studied as a continuous variable in relation to birth outcomes. We sought to evaluate the impact of PCI distance on outcomes associated with placental function and development of fetal growth restriction (FGR). STUDY DESIGN: This was a retrospective study of singleton gestations that underwent a fetal anatomy ultrasound from 2011-2013. The PCI was recorded as the distance in centimeters from the placental margin. Patients had FGR if the overall estimated fetal weight was <10 % for gestational age or abdominal circumference <5 % in the third trimester. Delivery, obstetric, and neonatal outcomes were obtained via medical chart review. Logistic and linear regression models were used to assess the impact of PCI distance on maternal and neonatal delivery outcomes. RESULTS: Of the 1443 women who met inclusion criteria, 93.6 % delivered at term. The mean (±SD) PCI distance was 4.4 ± 1.4 cm. There was no association between PCI and cesarean delivery, peripartum hemorrhage (PPH), pre-eclampsia, 5-min Apgar, or intrauterine fetal demise. PCI distance was statistically significantly shorter in patients requiring neonatal intensive care unit (NICU) admission (4.1 ± 1.5 cm vs. 4.4 ± 1.4 cm, p = 0.02) and was associated with lower birthweight (p = 0.01), though this association was no longer seen when corrected for gestational age. There were 3.5 % of patients who developed FGR; PCI distances from the placental edge were not significantly different for patients who developed FGR compared to those who did not (4.2 ± 1.4 cm vs. 4.5 ± 1.4 cm, p = 0.18). Furthermore, a receiver operating characteristic (ROC) curve for PCI had poor sensitivity (area under the curve [AUC] 0.57, 95 % CI 0.49-0.65). CONCLUSION: PCI distance at the time of fetal anatomic survey is significantly associated with NICU admission, though does not appear to impact rates of preterm birth, pre-eclampsia, PPH or cesarean delivery. PCI distance in singleton gestations does not appear to be predictive of FGR.

Study To Reduce Infection Prior to Elective Cesarean Deliveries (STRIPES): a randomized clinical trial of chlorhexidine.

BACKGROUND: Surgical site infections after cesarean delivery are a cause of maternal morbidity and are typically caused by skin microbial flora. Preadmission application of chlorhexidine gluconate using impregnated cloths may decrease surgical site infections by decreasing the abundance of microbial flora. OBJECTIVE: To determine whether the application of chlorhexidine gluconate cloths the night before and the morning of scheduled cesarean delivery decreases the risk of surgical site infections by 6 weeks postoperatively compared with placebo. STUDY DESIGN: In this single-center, double-blind, placebo-controlled trial, patients were randomized (1:1) to receive either Sage 2% chlorhexidine cloths or Sage Comfort Bath fragrance-free cloths (placebo) to apply to 6 skin sites on the body (neck, shoulders and chest, armpits, arm and hands, abdomen and groin, left leg and foot, right leg and foot, back and buttocks) the night before and after a shower the morning of scheduled cesarean delivery. Routine clinical and operative procedures were followed. The primary outcome was surgical site infections (superficial or deep incisional with or without organ space endometritis) by 6 weeks after cesarean delivery. The secondary outcomes were surgical site infections by 2 weeks and other wound-related complications by 2 and 6 weeks after cesarean delivery. RESULTS: From April 2015 to August 2019, 1356 patients were enrolled: 682 were assigned to the chlorhexidine group and 674 to the placebo group. The groups were similar in demographic and medical characteristics. A total of 14 patients were lost to follow-up before cesarean delivery (10 in chlorhexidine and 4 in placebo) and 33 were lost to follow-up after cesarean delivery (10 in chlorhexidine and 23 in placebo). Among the remaining 1309 (97%), no difference was found in surgical site infections by 6 weeks between the 2 groups (2.6% in chlorhexidine vs 3.7% in placebo; P=.24). There were no differences in secondary outcomes at 2 or 6 weeks and no differences in primary outcome in a per-protocol analysis. CONCLUSION: Preadmission use of chlorhexidine gluconate cloths compared with placebo does not reduce the risk of surgical site infection after scheduled cesarean deliveries. Following the standard of care guidelines results in a low risk of surgical site infections in this group of patients.

Renal cell carcinoma with inferior vena cava thrombus extending to the right atrium diagnosed during pregnancy.

Only one case of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus diagnosed and treated during pregnancy has been reported in the literature. In that report, the tumor thrombus extended to the infrahepatic IVC (level II tumor thrombus). In the present case, a 37-year-old woman with lupus anticoagulant antibodies was diagnosed with RCC and IVC tumor thrombus extending to the right atrium (level IV tumor thrombus) at 24 weeks of pregnancy. The fetus was safely delivered by cesarean section at 30 weeks of gestation. At 4 days later, an open right radical nephrectomy and IVC and right atrial thrombectomy were performed on cardiopulmonary bypass (CPB) once the patient's hemodynamic status had been optimized. Fetal and maternal concerns included the risk of a thromboembolic event (due to increased hypercoagulability from pregnancy, active malignancy, and lupus anticoagulant), intraoperative hemorrhage risk (due to extensive venous collaterals and anticoagulation), and fetal morbidity and mortality (due to fetal lung immaturity). Standardized guidelines for treatment of RCC with or without IVC tumor thrombus during pregnancy are unavailable due to the infrequency of such cases. Treatment decisions are therefore individualized and this case report may inform the management of future patients diagnosed with RCC with level IV tumor thrombus during pregnancy.

What could keep young people away from alcohol and cigarettes? Findings from the UK Household Longitudinal Study.

BACKGROUND: Adolescents are vulnerable to risky behaviours that are likely to co-occur. We examined whether happiness, awareness of alcohol- or smoking-related harm or the size of friendship networks would be longitudinally associated with young people's risky behaviours. METHODS: We used available cases (N=1,729) from adolescents aged between 10 and 15 who participated in waves 2 and 3 of the UK Longitudinal Household Study that has annually collected population representative data from 40,000 UK households. The outcome variable was patterns of cigarette and alcohol use among adolescents (1= persistent non-use; 2= ex-use; 3= initiation; 4= persistent use) that we derived by tabulating current alcohol or cigarette use at waves 2 and 3. Explanatory variables were scores on participants' perception of overall happiness, awareness of harm due to alcohol and cigarette use, and supportive friendship network size, collected at wave 2. Covariates were participants' sex, age, base level of self-reported health status, reported religious affiliation, and household social position. All estimates were corrected for the complex survey design and non-response. Multinomial logistic regression was used to test assumed associations by taking persistent cigarette and alcohol use as the reference category. RESULTS: Findings showed higher happiness scores were longitudinally associated with adolescents' persistent non-use (RRR=1.06, 95% CI=1.01-1.13). Awareness of alcohol or cigarette use-related harm was longitudinally associated with persistent non-use (RRR=1.24, 95% CI 1.15-1.35) as well as initiation of alcohol or cigarette use (RRR=1.21, 95% CI=1.11-1.32). CONCLUSION: Joint interventions to promote happiness and harm awareness could help young adolescents from engaging with drinking alcohol or smoking cigarettes.

Mitochondrial gene expression profiles are associated with intrahepatic cholestasis of pregnancy.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) affects 0.2-2% of pregnant women. While the maternal clinical course of ICP is usually benign, the fetal effects can be severe spanning from spontaneous preterm birth to fetal demise to long term effects on the health of the progeny. ICP is characterized by high maternal serum levels of bile acids and placental and hepatic bile acids accumulation. Intrahepatic cholestasis, in the non-pregnant state, has been also linked to alterations of the mitochondrial activity attributed to high oxidative stress rates driven by high intracellular bile acids concentrations. Here we explored the hypothesis that elevated bile acid levels of ICP modify the placental mitochondrial activity. METHODS: By using a set of 12 ICP and 12 control placenta samples, we assessed the expression of all 13 mitochondrial-encoded protein-coding genes and the mitochondrial DNA (mtDNA) relative abundance by real-time PCR. We also assessed the oxidative stress status by measuring DNA damage by ELISA. RESULTS: We determined that: 1) the expression of MT-ND4L (+53% - p < 0.01), MT-ND4 (-19%-0.05 < p ≤ 0.01), MT-ND5 (+40% - p < 0.01), MT-CYTB (+35% - p < 0.01) is associated with ICP; 2) the mtDNA relative abundance is not associated with ICP (0.098 in ICP vs 0.118 in controls - p > 0.05); 3) the oxidative stress status is associated with ICP (4403.9 pM 8-oxo-dG/µg DNA in ICP vs 3809.8 pM 8-oxo-dG/µg DNA in controls - p < 0.01). DISCUSSION: This preliminary study suggests that mitochondria in placenta respond to high oxidative stress to modify their gene expression which may play an important role in the pathophysiology of ICP.

The utility of screening for historical risk factors for preterm birth in women with known second trimester cervical length.

OBJECTIVE: To evaluate for the presence of risk factors (RFs) for preterm birth (PTB) in women without prior PTB having second trimester cervical length (CL) screening, and to estimate the utility of RF screening. METHODS: "Low-risk" singletons were prospectively screened with midtrimester transvaginal ultrasound CL. Prior PTB, intrauterine fetal demise and lethal anomalies were excluded. Women were analyzed based on second trimester CL (<25 mm versus ≥25 mm) and the presence of RFs for PTB. A p-value of < 0.05 was considered significant. RESULTS: A total of 639 women were screened; 8% had CL <25 mm. Ninety-eight percent of women with CL <25 mm and 95% of women with CL ≥25 mm had RFs for PTB. Five percent of women with a CL ≥25 mm delivered preterm as compared to 18% with CL <25 mm (p < 0.01). Treatment of cervical dysplasia, drug use during the pregnancy and unmarried status were significantly more common in women with CL <25 mm than CL ≥25 mm. When data were analyzed by CL, the presence of additional RFs did not add to the prediction of PTB <37 weeks. DISCUSSION: Over 95% of singleton gestations without prior PTB have ≥1 other RF for PTB. In women without prior PTB, assessment of other PTB RFs does not add to prediction of PTB provided by CL alone.

Enfermedad hereditaria en pacientes menores de 21 años con feocromocitoma "aparentemente" esporádico / Hereditary disease in patients younger than 21 years of age with ’apparently’ sporadic pheochromocytoma

INTRODUCCION: Los feocromocitomas son tumores productores de catecolaminas, que durante mucho tiempo fueron considerados esporádicos. Actualmente, se sabe que pueden ser familiares, como parte de neoplasia endocrina múltiple tipo 2 A o B, causada por mutaciones en el protooncogen RET (Rearregement during Transfection), enfermedad de Von Hippel Lindau (VHL) causada por mutaciones en el gen supresor VHL, neurofibromatosis tipo 1 o síndromes de paraganglioma familiar (PGL) 1, 3 y 4, causados por mutaciones en las subunidades D, C o B de la succinato deshidrogenada (SDHD, SDHC, SDHB).OBJETIVO: Evaluar la presencia de alteraciones en los genes susceptibles de enfermedad hereditaria en pacientes con diagnóstico bioquímico y anatomopatológico de feocromocitoma.METODOS: Se analizó a 69 pacientes <21 años. Para el estudio de biología molecular se realizó la extracción de ADN de sangre periférica, la amplificación por PCR, el screening por SSCP (single strand conformation polymorfism) y la confirmación por secuenciación y/o digestión enzimática. Se realizó la evaluación clínica, la medición de las catecolaminas urinarias, la localización y el tratamiento del tumor.RESULTADOS: Tuvieron fenotipo sindrómico o fueron familiares 14/69 pacientes. Tuvieron feocromocitoma aparentemente esporádico 55/69. En 33/55 pacientes se realizaron los estudios de biología molecular. Se identificaron mutaciones en 22/33 (67%): 17 en VHL (52%) y 5 en SDHB (15%). No se encontraron mutaciones en el RET ni en SDHD. En cuanto a la localización del tumor, en los pacientes con VHL predominó la bilateralidad (11/17) y en los esporádicos la mayoría fue unilateral (7/11). El porcentaje de tumores extraadrenales y malignos fue mucho mayor entre los pacientes con mutaciones del gen de SDHB (3/4).CONCLUSIONES: Es importante realizar el estudio genético en pacientes jóvenes con feocromocitoma aparentemente esporádico, dado que existe una alta prevalencia de mutaciones, entre las que predomina la del gen de VHL

INTRODUCTION: Pheochromocytomas are catecholamine secreting tumors, which have been traditionally considered sporadic. Nowadays, familial pheochromocytomas are found to be more common due to their association with multiple endocrine neoplasia type 2A or B caused by mutations of the RET gene, von Hippel-Lindau disease (VHL) caused by mutations of the suppressor gen VHL, neufibromatosis type 1, and familial paraganlioma (PGL) 1, 3 and 4 syndromes caused by mutations of the gene coding for D, B and C subunits of succinate dehydrogenase (SDHD, SDHB and SDHC).OBJECTIVE: To evaluate the presence of mutations in any of the susceptible genes in patients with biochemical and anatomopathological diagnosis of pheochromocytoma.METHODS: The studies were performed in 69 patients younger than 21 years of age. They included clinical examination, measurement of urinary catecholamines, localization of the tumor and treatment. Molecular biology analyses were carried out in DNA from peripheral blood, PCR (polymerase chain reaction), amplification, (SSCP) single strand conformation polymorfism screening, and confirmed by sequencing and/or enzymatic digestion.RESULTS: 14/69 patients were relatives or had clinical features of familial disease. 55/69 had apparently sporadic pheochromocytoma. In 33/55 patients molecular biology analyses were carried out. 22/33 (67%) presented germ-line mutations: 11/22 (52%) had VHL mutation and 5/22 (15%) SDHB mutations. Neither SDHD nor RET mutations were found. Regarding the localization of the tumores, 11 patients with VHL presented bilateral tumors, and 7/11 patients with sporadic tumors showed unilateral pheochromocytoma. Extra-adenal and malignant tumors were much more frequend among patients with SDHB gene mutations (3/4).CONCLUSIONS: The high prevalence of mutations, mainly in the VHL gene, highlights the importance of performing genetic studies in young patients with apparently sporadic pheochromocytoma.

Enfermedad hereditaria en pacientes menores de 21 años con feocromocitoma "aparentemente" esporádico / Hereditary disease in patients younger than 21 years of age with apparently sporadic pheochromocytoma

INTRODUCCION: Los feocromocitomas son tumores productores de catecolaminas, que durante mucho tiempo fueron considerados esporádicos. Actualmente, se sabe que pueden ser familiares, como parte de neoplasia endocrina múltiple tipo 2 A o B, causada por mutaciones en el protooncogen RET (Rearregement during Transfection), enfermedad de Von Hippel Lindau (VHL) causada por mutaciones en el gen supresor VHL, neurofibromatosis tipo 1 o síndromes de paraganglioma familiar (PGL) 1, 3 y 4, causados por mutaciones en las subunidades D, C o B de la succinato deshidrogenada (SDHD, SDHC, SDHB).OBJETIVO: Evaluar la presencia de alteraciones en los genes susceptibles de enfermedad hereditaria en pacientes con diagnóstico bioquímico y anatomopatológico de feocromocitoma.METODOS: Se analizó a 69 pacientes <21 años. Para el estudio de biología molecular se realizó la extracción de ADN de sangre periférica, la amplificación por PCR, el screening por SSCP (single strand conformation polymorfism) y la confirmación por secuenciación y/o digestión enzimática. Se realizó la evaluación clínica, la medición de las catecolaminas urinarias, la localización y el tratamiento del tumor.RESULTADOS: Tuvieron fenotipo sindrómico o fueron familiares 14/69 pacientes. Tuvieron feocromocitoma aparentemente esporádico 55/69. En 33/55 pacientes se realizaron los estudios de biología molecular. Se identificaron mutaciones en 22/33 (67%): 17 en VHL (52%) y 5 en SDHB (15%). No se encontraron mutaciones en el RET ni en SDHD. En cuanto a la localización del tumor, en los pacientes con VHL predominó la bilateralidad (11/17) y en los esporádicos la mayoría fue unilateral (7/11). El porcentaje de tumores extraadrenales y malignos fue mucho mayor entre los pacientes con mutaciones del gen de SDHB (3/4).CONCLUSIONES: Es importante realizar el estudio genético en pacientes jóvenes con feocromocitoma aparentemente esporádico, dado que existe una alta prevalencia de mutaciones, entre las que predomina la del gen de VHL

INTRODUCTION: Pheochromocytomas are catecholamine secreting tumors, which have been traditionally considered sporadic. Nowadays, familial pheochromocytomas are found to be more common due to their association with multiple endocrine neoplasia type 2A or B caused by mutations of the RET gene, von Hippel-Lindau disease (VHL) caused by mutations of the suppressor gen VHL, neufibromatosis type 1, and familial paraganlioma (PGL) 1, 3 and 4 syndromes caused by mutations of the gene coding for D, B and C subunits of succinate dehydrogenase (SDHD, SDHB and SDHC).OBJECTIVE: To evaluate the presence of mutations in any of the susceptible genes in patients with biochemical and anatomopathological diagnosis of pheochromocytoma.METHODS: The studies were performed in 69 patients younger than 21 years of age. They included clinical examination, measurement of urinary catecholamines, localization of the tumor and treatment. Molecular biology analyses were carried out in DNA from peripheral blood, PCR (polymerase chain reaction), amplification, (SSCP) single strand conformation polymorfism screening, and confirmed by sequencing and/or enzymatic digestion.RESULTS: 14/69 patients were relatives or had clinical features of familial disease. 55/69 had apparently sporadic pheochromocytoma. In 33/55 patients molecular biology analyses were carried out. 22/33 (67%) presented germ-line mutations: 11/22 (52%) had VHL mutation and 5/22 (15%) SDHB mutations. Neither SDHD nor RET mutations were found. Regarding the localization of the tumores, 11 patients with VHL presented bilateral tumors, and 7/11 patients with sporadic tumors showed unilateral pheochromocytoma. Extra-adenal and malignant tumors were much more frequend among patients with SDHB gene mutations (3/4).CONCLUSIONS: The high prevalence of mutations, mainly in the VHL gene, highlights the importance of performing genetic studies in young patients with apparently sporadic pheochromocytoma.

Efectividad de la psicoterapia y su relación con la alianza terapéutica / Effectiveness of the psychotherapy and its relation with the therapeutic alliance

En este estudio se evalúa la efectividad de la psicoterapia individual realizada por terapeutas noveles en la Clínica Psicológica de la Universidad de La Frontera (Temuco - Chile) y su relación con la alianza terapéutica. La investigación es de carácter cuantitativo, con diseño de grupo único y evaluaciones al inicio y término de la terapia. En el estudio participaron 23 consultantes, cuyos procesos psicoterapéuticos eran conducidos por 11 estudiantes de los últimos niveles de la Carrera de Psicología, que realizaban su primera experiencia en atención psicoterapéutica supervisada, o se encontraban efectuando su práctica profesional. Los instrumentos utilizados fueron las versiones adaptadas para Chile del Outcome Questionnaire (OQ-45.2) de De la Parra y Von Bergen (2000, 2002) que permite evaluar el nivel de cambio en el curso de la terapia y sus resultados finales y del Working Alliance Inventory (Inventario de Alianza de Trabajo, IAT-P) de Santibáñez (2001) que evalúa la alianza terapéutica desde la perspectiva del paciente. Los resultados informan diferencias significativas entre la primera y última aplicación del OQ-45.2. Los puntajes obtenidos en el IAT-P están ubicados en los dos tercios superiores de la escala, observándose una restricción de rango con sesgo positivo. Se evidencia una asociación significativa entre la alianza terapéutica percibida por el paciente y el resultado de la psicoterapia, tanto en el puntaje total de la escala OQ-45.2, como en la Subescala de Síntomas. Estos resultados son discutidos considerando la investigación actual en el área y el trabajo realizado por terapeutas noveles.

The present study was aimed to assess the effectiveness of individual psychotherapy undertaken at the Psychological Clinic of the Universidad de La Frontera (Temuco, Chile) and its relationship with the therapeutic alliance. The investigation involved 23 adult patients with neurotic symptoms. Their therapeutic processes were carried out by 11 trainee students from the regular psychology training program. Out of these, 4 therapists were performing their first supervised psychotherapeutic experience, and 7 therapists were undertaking their professional training using either a psychodynamic or a humanistic- experiential approach. The therapeutic processes considered in this study lasted between 5 and 42 sessions, comprising the following closure modalities: agreed closure between the patient and therapist because of the fulfillment of objectives, closure requested by the patient, and withdrawal of the therapeutic process. The instruments used were the Outcome Questionnaire (OQ-45.2) adapted for Chilean population by De la Parra and Von Bergen (2000, 2002), an instrument that allows to evaluate the level of change in the final course of the therapy and its outcomes; and the Working Alliance Inventory (Inventario de Alianza Terapéutica, IAT-P) adapted for Chilean population by Santibánez (2001), an instrument that evaluates the level of therapeutic alliance from the perspective of the patient. The study was quantitative in nature, with a unique group design and evaluations at the beginning and at the end of the therapy. For each patient, the OQ-45.2 was administered at the end of the first, and after the last psychotherapy session. In addition, the IAT-P was administered once, at the fourth session. In order to assess the pre-post psychotherapy differences, a samples-related t test was performed. In addition, a Reliable Change Index was calculated using scores of the first and final OQ-45.2 administration; and finally, the percentage of patients with clinically significant change, was estimated. The administration of the IAT-P showed a restriction of range with positive bias both, on overall total scale scores as well on each subscale score. For this reason, using the median, two subgroups for the overall IAT were created. Also, two subgroups were generated for each subscale: a subgroup of subjects with scores higher than the median and a subgroup of subjects with scores below the median. Then, by using the Mann-Whitney U test, the Reliable Change Index from the groups with high or low levels of alliance were compared. Results of this study showed significant differences between the first and last application of the OQ-45.2. In order to estimate whether the change was clinically significant, cut-off scores and Reliable Change Index were used. In the OQ-45.2 scale, 17 patients left the clinical group, 12 people met the Reliable Change Index criterion, and 8 people showed a clinically significant change. In relation to the closure modality, 7 patients with clinically significant change ended the psychotherapy with a discharge given by the therapist, while one requested the closure of the therapy. Scores from the IAT-P were located in the upper two thirds of the scale. The Bond Subscale had the highest mean, while Tasks and Goals got a slightly lower value. With respect to the main issue, it was found a significant association between therapeutic alliance and the outcome of the psychotherapy both, on overall total scale scores of the OQ-45.2 as well Symptoms Scale of the same instrument. Results showed that the alliance between therapist and the patient especially helped to reduce patient's symptoms. In addition, it was evident that students in training were able to establish good alliance with their patients, and thus to promote the achievement of the therapeutic outcome. These results are discussed taking into account current research on this topic.

Prediction of preterm birth: cervical sonography.

The cervix has to open to allow vaginal birth. Ultrasound has now shown that this lower part of the uterus begins to show changes weeks before eventual birth. Only transvaginal ultrasound should be used to evaluate the cervix for prediction of preterm birth (PTB). The shortest best cervical length (CL) is the most effective measurement for clinical use. Proper technique is paramount for accurate results. The risk of PTB increases with ever shorter CL (<25 mm). Other factors that must be carefully considered when using CL for prediction of PTB are number of fetuses, risk factors for PTB, and gestational age at screening.

Puerto Rico experience with plugs in the treatment of anal fistulas.

BACKGROUND: Anorectal fistula is a common problem that affects quality of life. Main objective of therapy has been to eradicate the fistula tract while preserving fecal continence. Latest good results for anal fistula treatment have been an anal fistula plug. This study was undertaken to determine if these results could be reproduced in Puerto Rico. METHOD: From January 2003 to January 2008, two experienced colorectal surgeons performed this new operation in 23 consecutive patients. A multivariable analysis was undertaken including age, sex, location of the fistula, previous surgeries, Seton placement before the insertion of the plug, continence pre and post operation, as well as close follow up. No patient with inflammatory bowel disease was included. RESULTS: We had a good result or healing of the fistula in 14 of 23 patients for a success rate of 60%. We had a subgroup of patients who did slightly better and had a healing rate of 66% compared to the 60% of the whole group. It appears to be a trend in favor of the Seton group but is not statically significant. We had 9 failures of 23 patients or 39%. Suppuration was noticed in three patients and all three had failures of the plug with recurrences. CONCLUSIONS: This new operation is another alternative to add to our armamentarium but we need to search for an operation that decreases the incidence of recurrences we had in our study while maintaining function of the sphincters.

Hermansky Pudlak syndrome: an unusual form of procto-colitis.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder consisting of oculocutaneous albinism, platelet dysfunction and systemic complications associated with lipofuscin deposition in the reticuloendothelial system. HPS has been associated with a granulomatous enterocolitis with pathologic features suggestive of Crohn's disease. It remains uncertain if HPS represents a truly distinct form of granulomatous enterocolitis. We report a series of two patients with HPS treated in Puerto Rico, and the results from medical and surgical intervention for gastrointestinal disease. Our experience with HPS patients has shown the difficult management of perineal disease similar in the management of Crohn's. However, complications from the bleeding diathesis necessitate caution during surgery and potential anesthesia complications. Furthermore, avoidance of a perineal wound is preferred, and when possible, ileostomies have fewer complications than colostomies as they do not involve the small bowel.

Variables inespecíficas en psicoterapia: [revisión] / Inespecific variables in psychoterapy: [revision]

Este artículo presenta una sistematización teórica de las variables inespecíficas que se han estudiado intervienen en el proceso psicoterapéutico.Se realiza una revisión de la investigación de proceso en psicoterapia y la influencia de los factores comunes en el cambio terapéutico, para finalizar con una descripción de los principales hallazgos respecto a las variables inespecíficas reportadas en la literatura: del consultante, del terapeuta y de la relación.

This paper presents a theoretical systematization of the non specific variables, that have been studied to intervene in the psychotherapy process. The article presents a review of the psychotherapy process research and its influence of the common factors in psychotherapeutic change. It finishes with a description to the principal findings about non specifics variables to the literature reports: to the patient, to the therapist and the therapeutic relationship.