Jacob Szejnfeld

Congenital Zika Virus Infection: Beyond Neonatal Microcephaly

Importance Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects. Objective To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil. Design, Setting, and Participants We observed 11 infants with congenital ZIKV infection from gestation to 6 months in the state of Paraíba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis. Main Outcomes and Measures Description of the major lesions caused by ZIKV congenital infection. Results Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and brain). Phylogenetic analyses showed an intrahost virus variation with some polymorphisms in envelope genes associated with different tissues. Conclusions and Relevance Combined findings from clinical, laboratory, imaging, and pathological examinations provided a more complete picture of the severe damage and developmental abnormalities caused by ZIKV infection than has been previously reported. The term congenital Zika syndrome is preferable to refer to these cases, as microcephaly is just one of the clinical signs of this congenital malformation disorder.

Congenital Brain Abnormalities and Zika Virus: What the Radiologist Can Expect to See Prenatally and Postnatally

Purpose To document the imaging findings associated with congenital Zika virus infection as found in the Instituto de Pesquisa in Campina Grande State Paraiba (IPESQ) in northeastern Brazil, where the congenital infection has been particularly severe. Materials and Methods From June 2015 to May 2016, 438 patients were referred to the IPESQ for rash occurring during pregnancy or for suspected fetal central nervous system abnormality. Patients who underwent imaging at IPESQ were included, as well as those with documented Zika virus infection in fluid or tissue (n = 17, confirmed infection cohort) or those with brain findings suspicious for Zika virus infection, with intracranial calcifications (n = 28, presumed infection cohort). Imaging examinations included 12 fetal magnetic resonance (MR) examinations, 42 postnatal brain computed tomographic examinations, and 11 postnatal brain MR examinations. Images were reviewed by four radiologists, with final opinion achieved by means of consensus. Results Brain abnormalities seen in confirmed (n = 17) and presumed (n = 28) congenital Zika virus infections were similar, with ventriculomegaly in 16 of 17 (94%) and 27 of 28 (96%) infections, respectively; abnormalities of the corpus callosum in 16 of 17 (94%) and 22 of 28 (78%) infections, respectively; and cortical migrational abnormalities in 16 of 17 (94%) and 28 of 28 (100%) infections, respectively. Although most fetuses underwent at least one examination that showed head circumference below the 5th percentile, head circumference could be normal in the presence of severe ventriculomegaly (seen in three fetuses). Intracranial calcifications were most commonly seen at the gray matter-white matter junction, in 15 of 17 (88%) and 28 of 28 (100%) confirmed and presumed infections, respectively. The basal ganglia and/or thalamus were also commonly involved with calcifications in 11 of 17 (65%) and 18 of 28 (64%) infections, respectively. The skull frequently had a collapsed appearance with overlapping sutures and redundant skin folds and, occasionally, intracranial herniation of orbital fat and clot in the confluence of sinuses. Conclusion The spectrum of findings associated with congenital Zika virus infection in the IPESQ in northeastern Brazil is illustrated to aid the radiologist in identifying Zika virus infection at imaging. (©) RSNA, 2016 Online supplemental material is available for this article.

Flow Pattern and Vascular Resistive Index as Predictors of Malignancy Risk in Thyroid Follicular Neoplasms

The purpose of this study was to evaluate whether flow pattern and resistive index (RI) are useful parameters for distinguishing benign from malignant thyroid follicular neoplasms (FNs).

Risk factors for osteoporotic fractures and low bone density in pre and postmenopausal women

OBJECTIVE To estimate the prevalence and analyze risk factors associated to osteoporosis and low-trauma fracture in women. METHODS Cross-sectional study including a total of 4,332 women older than 40 attending primary care services in the Greater São Paulo, Southeastern Brazil, between 2004 and 2007. Anthropometrical and gynecological data and information about lifestyle habits, previous fracture, medical history, food intake and physical activity were obtained through individual quantitative interviews. Low-trauma fracture was defined as that resulting from a fall from standing height or less in individuals 50 years or older. Multiple logistic regression models were designed having osteoporotic fracture and bone mineral density (BMD) as the dependent variables and all other parameters as the independent ones. The significance level was set at p<0.05. RESULTS The prevalence of osteoporosis and osteoporotic fractures was 33% and 11.5%, respectively. The main risk factors associated with low bone mass were age (OR=1.07; 95% CI: 1.06;1.08), time since menopause (OR=2.16; 95% CI: 1.49;3.14), previous fracture (OR=2.62; 95% CI: 2.08;3.29) and current smoking (OR=1.45; 95% CI: 1.13;1.85). BMI (OR=0.88; 95% CI: 0.86;0.89), regular physical activity (OR=0.78; 95% CI: 0.65;0.94) and hormone replacement therapy (OR=0.43; 95% CI: 0.33;0.56) had a protective effect on bone mass. Risk factors significantly associated with osteoporotic fractures were age (OR=1.05; 95% CI: 1.04;1.06), time since menopause (OR=4.12; 95% CI: 1.79;9.48), familial history of hip fracture (OR=3.59; 95% CI: 2.88;4.47) and low BMD (OR=2.28; 95% CI: 1.85;2.82). CONCLUSIONS Advanced age, menopause, low-trauma fracture and current smoking are major risk factors associated with low BMD and osteoporotic fracture. The clinical use of these parameters to identify women at higher risk for fractures might be a reasonable strategy to improve the management of osteoporosis.OBJETIVO: Estimar a prevalencia e analisar os fatores de risco associados com osteoporose e fratura por baixo impacto entre mulheres. METODOS: Estudo transversal realizado com 4.332 mulheres acima de 40 anos de idade provenientes de atendimento primario de saude na area metropolitana da Grande Sao Paulo, SP, entre 2004 e 2007. Dados antropometricos e ginecologicos e relativos a habitos de vida, fratura previa, antecedentes pessoais, ingestao alimentar e atividade fisica foram avaliados por meio de entrevista individual e quantitativa. Fratura por baixo impacto foi definida como decorrente de queda da propria altura ou menos em individuos com mais de 50 anos de idade. Modelos de regressao multivariada e logistica analisaram, respectivamente, a densidade ossea e a fratura por osteoporose como variaveis dependentes e todas as outras como independentes. O nivel de significância estatistica estabelecido foi p < 0,05. RESULTADOS: A prevalencia de osteoporose e de fraturas por fragilidade ossea foi de 33% e 11,5%, respectivamente. Os principais fatores de risco associados com baixa densidade ossea foram idade (OR = 1,07; IC 95%: 1,06;1,08), menopausa (OR = 2,16; IC 95%: 1,49;3,14), fratura previa (OR = 2,62; IC 95%: 2,08;3,29) e tabagismo atual (OR = 1,45; IC 95%: 1,13;1,85). Por outro lado, elevado IMC (OR = 0,88; IC 95%: 0,86;0,89), atividade fisica regular (OR = 0,78; IC 95%: 0,65;0,94) e terapia hormonal atual (OR = 0,43; IC 95%: 0,33;0,56) desempenharam papel protetor. Os fatores de risco significativamente relacionados com fratura por osteoporose foram idade (OR = 1,05; IC 95%: 1,04;1,06), menopausa (OR = 4,12; IC 95%: 1,79;9,48), historia familiar de fratura de quadril (OR = 3,59; IC 95%: 2,88;4,47) e baixa densidade ossea (OR = 2,28; IC 95%: 1,85;2,82). CONCLUSOES: Idade avancada, menopausa, fratura previa por baixo impacto e tabagismo atual sao os principais fatores de risco associados com baixa densidade ossea, a qual se associa com as fraturas por fragilidade ossea. O uso clinico desses parâmetros para identificar mulheres de maior risco para fraturas pode ser uma estrategia interessante para melhorar a abordagem da osteoporose.

A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid

In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease, 30 patients with body mass indices higher than 25, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyltransferase (gamma-GT) at least more than 1.5 times the upper limit of normality, and hepatic steatosis demonstrated by ultrasonography were randomized into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1 ursodeoxycholic acid for three months. Abdominal computed tomography was performed to quantify hepatic fat content, which was significantly correlated with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass index remained stable for both groups throughout the study, but a significant reduction in mean ( +/- SEM) serum levels of ALT, AST and gamma-GT was observed only in the treated group (ALT = 81.2 +/- 9.7, 44.8 +/- 7.7, 48.1 +/- 7.7 and 52.2 +/- 6.3 IU/l at the beginning and after the first, second and third months, respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 +/- 9.8, 54.5 +/- 7, 60 +/- 7.6 and 43.7 5 IU/l, respectively. No alterations in hepatic lipid content were observed in these patients by computed tomography examination (50.2 +/- 4.2 Hounsfield units (HU) at the beginning versus 51.1 +/- 4.1 HU at the third month). These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content.

CT quantification of effects of thalidomide in patients with metastatic renal cell carcinoma

OBJECTIVE Our objective was to use functional CT to evaluate the effects of thalidomide in patients with metastatic renal cell carcinoma. SUBJECTS AND METHODS Patients with proven metastatic renal cell carcinoma were examined prospectively with functional CT. Functional CT studies (cine mode, 4 x 5 mm) were performed through the tumor after i.v. administration of a bolus of contrast material before and every 12 weeks after treatment with thalidomide. Quantitative values for blood flow, blood volume, mean transit time, and permeability-surface area product were calculated with commercial software. The average difference in percentage change in functional CT parameters from pretreatment to 12 and 24 weeks after treatment and the median difference in percentage change in functional CT parameters between response groups were assessed. We also tested whether percentage changes in functional CT parameters 12 weeks after treatment correlated with time to progression of disease and size of the perfused lesion. RESULTS Sixteen patients with a total of 23 tumors underwent at least one follow-up functional CT examination. Blood flow, blood volume, and permeability-surface area product decreased significantly 12 weeks (-18%, p = 0.0039; -15%, p = 0.0350; -24%, p = 0.0010) and 24 weeks (-28%, p = 0.017; -19%, p = 0.0300; -25%, p = 0.0031) after treatment with thalidomide. Time to progression correlated significantly with percentage change in blood flow (r = -0.34; p = 0.040) and permeability-surface area product (r = -0.36, p = 0.023) at 12 weeks. Responders had a significantly larger decrease in blood flow 12 weeks after treatment than did nonresponders (-29% vs -6%; p = 0.032). We also found a significant correlation between decrease in size of the perfused lesion and percentage decrease in blood flow 12 weeks after treatment (r = 0.50; p = 0.019). CONCLUSION Changes in functional CT parameters 12 weeks after treatment may be useful for monitoring the effects of thalidomide and predicting treatment outcome among patients with metastatic renal cell carcinoma. Further study with a larger clinical trial is needed.

Analysis by MRI of residual tumor after radiofrequency ablation for early stage breast cancer.

OBJECTIVE The objective of our study was to evaluate the effectiveness of MRI in the detection of possible residual lesions after radiofrequency ablation (RFA) in the treatment of breast cancer. SUBJECTS AND METHODS We prospectively evaluated 14 patients who had undergone ultrasound-guided core biopsies diagnostic of invasive ductal carcinoma (IDC; range of diameters, 1.0-3.0 cm) and then ultrasound-guided percutaneous RFA with sentinel node biopsy as the primary treatment. Breast MRI was performed 1 week before RFA to evaluate tumor extension and again 3 weeks after RFA to verify the presence of possible residual lesions. Conventional surgical resection of the tumors was performed 1 week after RFA. The MRI findings were compared with histopathologic analyses to confirm the presence or absence of residual tumor. RESULTS There was no residual enhancement in seven lesions on the postablation breast MRI scans. These findings were confirmed by negative histopathologic findings in the surgical specimens. The MRI scans of five patients showed small areas of irregular enhancement that corresponded to residual lesions. In the two remaining patients, we observed enhancement of almost the entire lesion, indicating that RFA had failed. CONCLUSION Breast MRI is effective in detecting residual lesions after RFA in patients with IDC.

New Trends in Diffusion-Weighted Magnetic Resonance Imaging as a Tool in Differentiation of Serous Cystadenoma and Mucinous Cystic Tumor: A Prospective Study

Background/Aims: Pancreatic cystic lesions are increasingly being recognized. Magnetic resonance imaging (MRI) is the method that brings the greatest amount of information about the morphologic features of pancreatic cystic lesions. To establish if diffusion-weighted MRI (DW-MRI) can be used as a tool to differentiate mucinous from nonmucinous lesions. Methods: Fifty-six patients with pancreatic cystic lesions (benign, n = 46; malignant, n = 10) were prospectively evaluated with DW-MRI in order to differentiate mucinous from nonmucinous lesions. Final diagnosis was obtained by follow-up (n = 31), surgery (n = 16) or endoscopic ultrasound-guided fine needle aspiration (n = 9). Serous cystadenoma was identified in 32 (57%) patients. Results: The threshold value established for the differentiation of mucinous from nonmucinous lesions was 2,230.06 s/mm2 for ADC of 700. DWI-MRI behavior between mucinous and nonmucinous groups revealed sensitivity, specificity, positive predictive value, negative predictive value and accuracy to be 80, 98, 92, 93 and 93%, respectively (p < 0.01, power of sample = 1.0). In the comparison of the diffusion behavior between mucinous (n = 13) and serous (n = 32) lesions, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 100, 97, 92, 100 and 98%, respectively (p < 0.01, power of sample = 1.0). The results of endoscopic ultrasound-guided fine needle aspiration were similar to those of DW-MRI. Conclusions: DW-MRI can be included as part of the array of tools to differentiate mucinous from nonmucinous lesions and can help in the management of pancreatic cystic lesions.

Endoscopic, ultrasonographic, and US-Doppler parameters as indicators of variceal bleeding in patients with schistosomiasis.

Bleeding from esophagogastric varices is a potentially deadly complication in patients with hepatosplenic schistosomiasis. The aim of this study is to establish indicators of variceal bleeding. We studied 40 patients with compensated hepatosplenic schistosomiasis and varices, analyzing four endoscopic (variceal size, red color signs, fundic varices, and congestive gastropathy), nine ultrasonographic (right and left hepatic lobe size, periportal and gallbladder wall thickness, portal and splenic veins diameter, spleen longitudinal axis and volume, and presence of collateral circulation), and five US-Doppler parameters (portal and splenic veins velocity and flow and portal vein congestion index). Patients were divided in two groups according to previous history of variceal bleeding. The group with bleeding episodes was again divided in two groups: with and without treatment, namely endoscopic sclerotherapy. All endoscopic parameters and two ultrasonographic (periportal thickness and portal vein diameter) were statistically different between the groups with and without previous bleeding. The likelihood index, adopted to determine the best parameters related to previous bleeding showed that the most important combinations are: gastropathy and red signs followed by portal vein diameter and variceal size. In conclusion, although aware of the limits of the statistical analysis due to the small number of patients, our results demonstrated that endoscopic and US parameters (isolated or combined) can identify patients with a high risk of variceal bleeding, allowing physicians to optimize prophylactic therapy.

Análise radiológica das alterações gastrintestinais após cirurgia de Fobi-Capella

OBJECTIVE: The present study was aimed at evaluating radiological findings of delayed postoperative upper gastrointestinal series in patients submitted to Fobi-Capella surgery. MATERIALS AND METHODS: Radiological studies of 41 patients, six to nine months following the surgery. RESULTS: The following pathological alterations have been found: hiatal hernia (17%), gastroesophageal reflux disease (19.5%) and sliding of the silastic ring (4.8%). Least frequent findings have been the following: enterocutaneous fistula (2.4%), stenosis of the gastric pouch outlet (2.4%), bezoar (2.4%), and non-visualization of the silastic ring caused by its removal due to patient intolerance (2.4%). Anatomical alterations resulting from the surgery have been clearly demonstrated. CONCLUSION: The present study could demonstrate anatomical alterations and complications resulting from Fobi-Capella surgery.