Depression Treatment in Pregnancy: Is It Safe, or Is It Not?

Prenatal depression carries substantial risks for maternal and fetal health and increases susceptibility to postpartum depression. Untreated depression in pregnancy is correlated with adverse outcomes such as an increased risk of suicidal ideation, miscarriage and neonatal growth problems. Notwithstanding concerns about the use of antidepressants, the available treatment options emphasize the importance of specialized medical supervision during gestation. The purpose of this paper is to conduct a brief literature review on the main antidepressant drugs and their effects on pregnancy, assessing their risks and benefits. The analysis of the literature shows that it is essential that pregnancy be followed by specialized doctors and multidisciplinary teams (obstetricians, psychiatrists and psychologists) who attend to the woman's needs. Depression can now be treated safely during pregnancy by choosing drugs that have no teratogenic effects and fewer side effects for both mother and child. Comprehensive strategies involving increased awareness, early diagnosis, clear guidelines and effective treatment are essential to mitigate the impact of perinatal depression.

Shedding of Syncytiotrophoblast-Derived Extracellular Vesicles Is Increased in Placenta Previa and Accreta Spectrum.

Placenta accreta spectrum (PAS) refers to excessive placental invasion into the maternal uterus and it is associated with high risk of obstetric haemorrhage and adverse maternal-neonatal outcomes. Currently, no specific circulating biomarkers of PAS have been identified. Given that in PAS disorders, the depth and the extension of placental invasion into the uterus are expected to be increased, in this study, we analysed plasma levels of syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with placenta previa (PP), at a high risk of PAS disorders, and pregnant women with normal placentation. Venous blood samples were collected from 35 women with ultrasonographic diagnosis of PP and 35 women with normal placentation, matched for gestational age. Plasma samples were ultracentrifuged at 120.000 g to collect extracellular vesicles (EVs). To identify and quantify plasma placenta-derived EVs (or STBEVs), EVs were analysed by flow cytometry using a monoclonal antibody against placental alkaline phosphatase (PLAP). Plasma levels of STBEVs were significantly higher in PP patients compared to controls. Plasma levels of STBEVs in women with PP and PAS showed a trend to a higher concentration compared to women with PP without PAS, although not reaching a statistical significance. Circulating STBEVs are potential candidates as biological markers to be integrated to ultrasonography in the antenatal screening programme for PAS. More studies are needed to confirm our observation in a larger cohort of patients and to analyse a possible association between high circulating levels of STBEVs and PAS.

Association between Plasma HLA-DR+ Placental Vesicles and Preeclampsia: A Pilot Longitudinal Cohort Study.

(1) Background: Preeclampsia (PE) usually presents with hypertension and proteinuria, related to poor placentation. Reduced maternal-fetal immunological tolerance is a possible trigger of inadequate placentation. Aberrant antigen expression of HLA-DR has been observed in the syncytiotrophoblast of PE patients. In this study, we analyzed plasma levels of Human Leukocyte Antigen (HLA)-DR+ syncytiotrophoblast-derived extracellular vesicles (STEVs) during the three trimesters of pregnancy in relation to PE onset. (2) Methods: Pregnant women underwent venous blood sampling during the three trimesters. STEVs were collected from plasma via ultracentrifugation (120,000 g) and characterized by Western blot, nanotracking analysis and flow cytometry for the expression of Placental Alkaline Phosphatase (PLAP), a placental-derived marker, and HLA-DR. (3) Results: Out of 107 women recruited, 10 developed PE. STEVs were detected in all three trimesters of pregnancy with a zenith in the second trimester. A significant difference was found between the non-PE and PE groups in terms of plasma levels of HLA-DR+ STEVs during all three trimesters of pregnancy. (4) Conclusions: More research is needed to investigate HLA-DR+ as a potential early marker of PE.

Healthcare associated infections in gynecologic oncology: clinical and economic impact.

OBJECTIVE: The purpose of this study was to assess the rate and type of infections in gynecological cancer patients. We also performed an economic analysis to provide an overview of costs related to healthcare associated infections. METHODS: We retrospectively collected data from culture samples at the site of infection from patients undergoing surgery or chemotherapy, admitted to the Gynecologic Oncology Unit, Fondazione Policlinico Agostino Gemelli IRCCS, from January 2017 to December 2018. We performed univariate and multivariate analyses to calculate potential risk factors for prolonged length of hospitalization. The average cost per patient was calculated, including the cost of hospital stay, operating room, medications, and diagnostic and invasive procedures. RESULTS: Among 5682 patients, 322 (5.6%) gynecological cancer patients with healthcare associated infections were identified. A total of 249 patients (77.3%) had undergone surgery in the previous 30 days and 73 (22.7%) patients were receiving chemotherapy. In the whole population, the most common healthcare associated infections were urinary infections (58%) and surgical wound infections (42.1%). In addition, 14.5% of patients had central venous catheter infections and 21.7% had blood stream infections. Median length of stay was 20 days (range 1-100). Among surgical patients, advanced age (odds ratio (OR) 1.233, 95% confidence interval (CI) 1.001 to 1.519, p=0.049), bowel resection (OR 2.659, 95% CI 1.493 to 4.735, p=0.001), surgical site infection (OR 10.447, 95% CI 1.143 to 95.5, p=0.038), and central venous catheter infection (OR 9.856, 95% CI 1.139 to 85.319, p=0.038) were independently associated with an increased risk of prolonged hospital stay (>20 days). The overall direct cost of healthcare associated infections was $6 273 852 per year. CONCLUSIONS: The infection rate in our population was 5.6%. The most common healthcare associated infections were urinary and surgical wound infections. Among surgical patients, advanced age, bowel resection, surgical site, and central venous catheter infection were associated with an increased length of hospitalization. Healthcare associated infections cause an increase in the length of stay after surgery and hospital costs.

Enoxaparin Increases D6 Receptor Expression and Restores Cytoskeleton Organization in Trophoblast Cells from Preeclampsia.

D6 is a scavenger receptor for CC chemokines expressed in the human placenta. It prevents excessive leukocyte tissue infiltration by internalizing chemokines through cytoskeleton-dependent intracellular transport. In preeclampsia (PE), the D6 receptor is overexpressed in trophoblast cells, but functionally impaired, due to cytoskeleton destructuring. Low molecular weight heparin (LMWH) represents a potential treatment for PE based on its anti-thrombotic and anti-inflammatory properties. Here, we investigated the effect of enoxaparin on D6 expression, and cytoskeleton organization primary cytotrophoblast cell cultures were obtained from the placentae of women with PE (n = 9) or uncomplicated pregnancy (n = 9). We demonstrated that enoxaparin is able to (i) increase D6 expression, and (ii) improve cytoskeletal fiber alignment in trophoblast cells from PE patients.

Circulating Placental Vesicles Carry HLA-DR in Pre-Eclampsia: A New Potential Marker of the Syndrome.

Background: Pre-eclampsia (PE) is a common disorder of pregnancy that usually presents with hypertension and proteinuria. The clinical presentation arises from soluble factors released into the maternal circulation from the placenta owing to the stress of syncytiotrophoblast, consequence of defective placentation occurring in the first half of pregnancy. Reduced tolerance of the semiallogeneic fetus by the maternal immune system has been proposed as first trigger leading to poor placentation. We previously observed aberrant expression of human leukocyte antigen (HLA)-DR molecules in the syncytiotrophoblast of a subset of women with PE. Aim of this study was to investigate abnormal expression of circulating HLA-DR in syncytiotrophoblast-derived extracellular vesicles (STBEVs) in women with PE compared to normal pregnant women. Methods: peripheral venous blood was collected from 22 women with PE and 22 normal pregnant women. Circulating STBEVs were collected by ultra-centrifugation (120000 g) and analyzed for the expression of HLA-DR and placental alkaline phosphatase (PLAP), a specific marker of the placenta, by Western blot analysis and flow cytometry. Results: circulating STBEVs positive for HLA-DR were observed in 64% of PE women while no HLA-DR positivity was detected in any of the controls (P<0.01). Conclusions: Aberrant expression of HLA-DR in circulating STBEVs is specifically associated to PE. Further studies are required: a) to define the role of aberrant placental expression of HLA-DR molecules in the pathogenesis of PE; b) evaluate a possible application of detecting circulating HLA-DR positive STBEVs in the diagnosis and prediction of PE in the first and second trimester of pregnancy.

Role of Human Leukocyte Antigens at the Feto-Maternal Interface in Normal and Pathological Pregnancy: An Update.

The successful maternal tolerance of the semi-allogeneic fetus provides an apparent immunologic paradox. Indeed, deep invasion of placental trophoblast cells into maternal uterine tissue and the following growth of the fetus have to be tolerated by a pregnant woman's immune system. Among the various possible protective mechanisms that may be involved in human pregnancy, the expression of a non-classical pattern of human leukocyte antigen (HLA) class I molecules and the complete lack of expression of HLA class II molecules in placental tissues seem to be the most relevant mechanisms of fetal escape from maternal immune recognition. The importance of HLA molecules in fetal toleration by the maternal immune system is highlighted by pregnancy complications occurring in cases of abnormal HLA molecule expression at the maternal-fetal interface. In this review, we summarize evidences about the role of placental HLA molecules in normal and pathological pregnancies.

Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy?

PURPOSE:: To evaluate the effects of mesenchymal stem cells on liver regeneration in rats following a 70% hepatectomy. METHODS:: Forty rats were subjected to 70% hepatectomy and then ~106 mesenchymal stem cells (test group), or saline solution (control group), were infused into their livers via the portal vein. Each treatment group was divided into early and late subgroups (euthanized 3 d and 5 d following the operation, respectively). Group comparisons of Albumin, aminotransaminases (AST, ALT), and Alcaline Phosphatase (AP) levels, proliferative index (ki-67+ straining), and mitotic cell counts were conducted. RESULTS:: No significant differences in liver regeneration rate, number of mitoses, proliferative index, or serum levels of albumin, AST, or AP were observed. ALT levels were higher in the test group than in the control group (p<.05). CONCLUSIONS:: Mesenchymal stem-cell therapy did not improve liver regeneration rate 3 d or 5 d after 70% hepatectomy in rats. Likewise, the therapy appeared not to affect liver function, proliferative index, or number of mitoses significantly.

Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy?

Abstract Purpose: To evaluate the effects of mesenchymal stem cells on liver regeneration in rats following a 70% hepatectomy. Methods: Forty rats were subjected to 70% hepatectomy and then ~106 mesenchymal stem cells (test group), or saline solution (control group), were infused into their livers via the portal vein. Each treatment group was divided into early and late subgroups (euthanized 3 d and 5 d following the operation, respectively). Group comparisons of Albumin, aminotransaminases (AST, ALT), and Alcaline Phosphatase (AP) levels, proliferative index (ki-67+ straining), and mitotic cell counts were conducted. Results: No significant differences in liver regeneration rate, number of mitoses, proliferative index, or serum levels of albumin, AST, or AP were observed. ALT levels were higher in the test group than in the control group (p<.05). Conclusions: Mesenchymal stem-cell therapy did not improve liver regeneration rate 3 d or 5 d after 70% hepatectomy in rats. Likewise, the therapy appeared not to affect liver function, proliferative index, or number of mitoses significantly.

Evaluation of systemic inflammatory responses in cholecystectomy by means of access. Single-port umbilical incision, transvaginal NOTES, laparoscopy and laparotomy.

PURPOSE: To evaluate and compare clinical and inflammatory responses to the surgical trauma caused by cholecystectomy via several access approaches: single-port umbilical incision (SILS), transvaginal natural orifice transluminal endoscopic surgery (NOTES), laparoscopy, and Laparotomy. METHODS: Twenty-eight female pigs were equally divided into four groups and submitted to cholecystectomy by single-port umbilical incision, transvaginal NOTES, laparoscopy, or Laparotomy. An additional five animals served as controls (sham group). Animals were monitored perioperatively regarding anesthesia and surgical procedure times, as well as for the presence of complications. Postoperatively, they were evaluated regarding time to ambulation and feeding, and the presence of clinical events. Procalcitonin, C-reactive protein (CRP), and AQUI feron-gamma (IFN-γ) measurements were performed before surgery and immediately, two days, and seven days after surgery. Animals were sacrificed and necropsied at seven days after surgery. RESULTS: All procedures were successfully performed as proposed in each group. Only minor complications, such as gallbladder perforation and bleeding from the liver bed, were observed during surgery in all groups. The vaginal NOTES group showed higher anesthesia and surgical procedure times compared to the other groups (p<0.001). No other between-group differences in perioperative or postoperative times, clinical evolution, or serum inflammatory markers were observed. Only adhesions were found on necropsy, with no differences between groups. CONCLUSION: The single-port umbilical and transvaginal NOTES access approaches were feasible and safe compared to laparoscopic and laparotomy for cholecystectomy.

Evaluation of systemic inflammatory responses in cholecystectomy by means of access. Single-port umbilical incision, transvaginal NOTES, laparoscopy and laparotomy

PURPOSE: To evaluate and compare clinical and inflammatory responses to the surgical trauma caused by cholecystectomy via several access approaches: single-port umbilical incision (SILS), transvaginal natural orifice transluminal endoscopic surgery (NOTES), laparoscopy, and Laparotomy.METHODS: Twenty-eight female pigs were equally divided into four groups and submitted to cholecystectomy by single-port umbilical incision, transvaginal NOTES, laparoscopy, or Laparotomy. An additional five animals served as controls (sham group). Animals were monitored perioperatively regarding anesthesia and surgical procedure times, as well as for the presence of complications. Postoperatively, they were evaluated regarding time to ambulation and feeding, and the presence of clinical events. Procalcitonin, C-reactive protein (CRP), and AQUI feron-gamma (IFN-γ) measurements were performed before surgery and immediately, two days, and seven days after surgery. Animals were sacrificed and necropsied at seven days after surgery.RESULTS: All procedures were successfully performed as proposed in each group. Only minor complications, such as gallbladder perforation and bleeding from the liver bed, were observed during surgery in all groups. The vaginal NOTES group showed higher anesthesia and surgical procedure times compared to the other groups (p<0.001). No other between-group differences in perioperative or postoperative times, clinical evolution, or serum inflammatory markers were observed. Only adhesions were found on necropsy, with no differences between groups.CONCLUSION: The single-port umbilical and transvaginal NOTES access approaches were feasible and safe compared to laparoscopic and laparotomy for cholecystectomy.

An evaluation of the protective effect of an infusion of chilled glucose solution on thermal injury of the bile ducts caused by radiofrequency ablation of the liver.

PURPOSE: To evaluate the protective effects of chilling the bile ducts with cold (5°C) 5% glucose solution (GS) during radiofrequency (RF) administration. METHODS: Twenty male pigs (3 mos. old; 25-30 kg) were subjected to RF delivery with chilling (experimental group, N=10) or without chilling (control group, N=10). Half of the animals in each group were euthanized immediately after the operation, and half were euthanized one week later. The following histological variables in relation to the bile ducts were evaluated by a pathologist (blind examiner): degenerative changes to the epithelium; epithelial necrosis; ulceration, regenerative changes of the epithelium; polymorphonuclear neutrophil infiltration; and thermal effects. RESULTS: The experimental group (88 bile ducts examined) showed reduced thermal damage relative to the control group (86 bile ducts examined) as demonstrated by significant differences in the following histopathological parameters: epithelial detachment of biliary epithelium (84.1% vs. 59.3%; p<0.006); elongation/palisade arrangement of nuclei (65.1% vs. 87.5%; p<0.001); pseudo-goblet cells (32.9% vs. 56.8%; p<0.001). CONCLUSION: Infusion of 5% glucose solution (5°C) has a protective effect on bile ducts subjected to heat (95-110°C, 12 min) from radiofrequency thermal ablation device.

An evaluation of the protective effect of an infusion of chilled glucose solution on thermal injury of the bile ducts caused by radiofrequency ablation of the liver

PURPOSE: To evaluate the protective effects of chilling the bile ducts with cold (5°C) 5% glucose solution (GS) during radiofrequency (RF) administration. METHODS: Twenty male pigs (3 mos. old; 25-30 kg) were subjected to RF delivery with chilling (experimental group, N=10) or without chilling (control group, N=10). Half of the animals in each group were euthanized immediately after the operation, and half were euthanized one week later. The following histological variables in relation to the bile ducts were evaluated by a pathologist (blind examiner): degenerative changes to the epithelium; epithelial necrosis; ulceration, regenerative changes of the epithelium; polymorphonuclear neutrophil infiltration; and thermal effects. RESULTS: The experimental group (88 bile ducts examined) showed reduced thermal damage relative to the control group (86 bile ducts examined) as demonstrated by significant differences in the following histopathological parameters: epithelial detachment of biliary epithelium (84.1% vs. 59.3%; p<0.006); elongation/palisade arrangement of nuclei (65.1% vs. 87.5%; p<0.001); pseudo-goblet cells (32.9% vs. 56.8%; p<0.001). CONCLUSION: Infusion of 5% glucose solution (5°C) has a protective effect on bile ducts subjected to heat (95-110°C, 12 min) from radiofrequency thermal ablation device. .

Analysis of differentially expressed genes in colorectal adenocarcinoma with versus without metastasis by three-dimensional oligonucleotide microarray.

BACKGROUND: Our objective was to examine how the gene expression profile of tumor tissue correlates with lymph node metastasis in patients with advanced colorectal adenocarcinoma (CRAC). METHODS: We studied 36 patients (20 men and 16 women, 22-90 years of age) treated for CRAC (classifications of T2, T3, or T4; histological grade of G1 or G2). Amplified tumor mRNA samples were exposed to 20,000 human sequence probes and digitized images of the hybridized samples were analyzed. RESULTS: On average, 2389 probes were detected above the background, with an average correlation R value of 0.19 between data from different patient groups (with or without lymph node invasion, colon or rectal, with or without angio-lymphatic invasion, with or without recurrence). Lymph node metastasis had a statistically significant signature according to Significance Analysis of Microarrays (SAM) and parametric t-tests, with a false discovery rate (FDR)=0.1% and p=0.001, respectively. Cross-correlation of these two tests identified 102 transcripts as being potentially related to node metastases, with fold changes in the range of 2.182-12.960. CONCLUSION: We identified 102 differentially expressed genes related to the presence of lymph node metastases in patients with advanced colorectal cancer.

O valor da fase sem contraste na tomografia computadorizada do abdome / The role of the unenhanced phase in the routine abdominal computed tomography

OBJETIVO: Determinar o valor agregado da fase sem meio de contraste da tomografia computadorizada do abdome em pacientes sem diagnóstico determinado ou em estadiamento tumoral. MATERIAIS E MÉTODOS: Estudo prospectivo e transversal em 100 pacientes consecutivos submetidos a tomografia computadorizada abdominal sem e com meio de contraste intravenoso. Dois examinadores avaliaram todos os exames, procurando estabelecer, através da fase com meio de contraste intravenoso (primeira análise) e posteriormente através da fase sem contraste (segunda análise), o diagnóstico principal e os secundários em função da indicação clínica do exame. Mediu-se a freqüência de mudança diagnóstica decorrente da análise combinada das fases pré- e pós-contraste intravenoso. Casos que tiveram mudança diagnóstica foram avaliados por especialistas clínicos para determinar se implicaria mudanças de conduta. RESULTADOS: Diagnósticos principal e secundário foram modificados em 1 e 18 casos, respectivamente (p = 1,000; p = 0,143). Os diagnósticos modificados foram: esteatose, definição de nódulo em adrenal, nefrolitíase, classificação de cistos renais e calcificação hepática. Nos casos em que a fase sem contraste modificou o diagnóstico, os especialistas mudaram sua conduta em 14/19 (73 por cento) dos pacientes (p = 0,038). CONCLUSÃO: A fase sem contraste não modificou significativamente o diagnóstico principal ou secundário. Porém, as mudanças nos diagnósticos secundários influenciaram na conduta adotada pelos especialistas.

OBJECTIVE: To determine the role of the unenhanced phase of abdominal computed tomography in patients without a definite diagnosis or undergoing tumor staging. MATERIALS AND METHODS: A prospective and transversal study was developed with 100 consecutive patients submitted to unenhanced and contrast-enhanced abdominal computed tomography. Two observers evaluated all the computed tomography images in the contrast-enhanced phase (first analysis) and, later, in the unenhanced phase (second analysis) in an attempt to establish the primary and secondary diagnoses as a function of the clinical indication for the study. The frequency of changes in the diagnoses resulting from a combined analysis of the images in the pre- and post-contrast phases was evaluated. Cases with changes in the diagnosis were reviewed by clinical specialists for determining possible changes in the therapeutic approach. RESULTS: Primary and secondary diagnoses were changed in respectively 1 and 18 cases (p = 1.000; p = 0.143) as follows: steatosis, adrenal nodules, nephrolithiasis, renal cysts and hepatic calcification. In the cases where the unenhanced phase changed the diagnosis, the specialists changed the therapeutic approach in 14 of the 19 patients (73 percent) (p = 0.038). CONCLUSION: No significant change was observed in the primary or secondary diagnosis as a result of the findings in the unenhanced phase. However, changes in secondary diagnoses affected the therapeutic approach adopted by the specialists.

Consumo de medicamentos com um grupo populacional da área urbana de Salvador-BA / Consumption of medicines in a population group of the urban area of Salvador-Bahia

O presente estudo teve por objetivo avaliar o consumo de medicamentos em um grupo populacional da cidade de Salvador. O material foi obtido através de entrevistas domiciliares a uma amostra de 609 indivíduos, utilizando-se um questionário que investigou a relaçäo do consumo e da prescriçäo médica com faixa etária, sexo, escolaridade, inserçäo produtiva e cobertura previdenciária. Quase a totalidade (98%) dos domicílios visitados possuía medicamentos em estoque. Os dados revelaram alta prevalência do consumo de medicamentos (61,7%), num período de apenas 15 dias, sendo que, entre os consumidores, mais da metade utilizou algum item medicamentoso sem prescriçäo médica. Näo se observou qualquer associaçäo entre consumo de medicamentos e sexo, enquanto que se verificaram maiores taxas entre crianças e idosos. Encontrou-se, também, uma associaçäo de nível educacional, inserçäo produtiva e cobertura previdenciária com o consumo de medicamentos prescritos e com automedicaçäo. Os resultados säo discutidos, destacando-se as suas relaçöes com a precariedade do sistema de saúde e com o processo mais amplo de medicalizaçäo da sociedade brasileira