Gender differences in workplace violence against physicians and nurses in Latin America: a survey from the Interamerican Society of Cardiology.

OBJECTIVES: To evaluate gender differences in workplace violence (WPV) against physicians and nurses in Latin America. STUDY DESIGN: Cross-sectional study. METHODS: A cross-sectional electronic survey was conducted between January 11 and February 28, 2022. A prespecified gender analysis was performed. RESULTS: Among the 3056 responses to the electronic survey, 57% were women, 81.6% were physicians, and 18.4% were nurses. At least one act of violence was experienced by 59.2% of respondents, with verbal violence being the most common (97.5%). Women experienced more WPV than men (65.8% vs 50.4%; P < 0.001; odds ratio [OR]: 1.89; 95% confidence interval [CI]: 1.63-2.19). Women were more likely to report at least one episode of WPV per week (19.2% vs 11.9%, P < 0.001), to request for psychological help (14.5% vs 9%, P = 0.001) and to experience more psychosomatic symptoms. In addition, women were more likely to report having considered changing their job after an aggression (57.6% vs 51.3%, P = 0.011) and even leaving their job (33% vs 25.7%, P = 0.001). In a multivariate analysis, being a woman (OR: 1.76), working in emergency departments (OR: 1.99), and with COVID-19 patients (OR: 3.3) were independently associated with more aggressive interactions, while older age (OR: 0.95) and working in a private setting (OR: 0.62) implied lower risk. CONCLUSIONS: Women are more likely to experience WPV and to report more psychosomatic symptoms after the event. Preventive measures are urgently needed, with a special focus on high-risk groups such as women.

Genotype-phenotype correlations in fetuses and neonates with autosomal recessive polycystic kidney disease.

The prognosis of autosomal recessive polycystic kidney disease is known to correlate with genotype. The presence of two truncating mutations in the PKHD1 gene encoding the fibrocystin protein is associated with neonatal death while patients who survive have at least one missense mutation. To determine relationships between genotype and renal and hepatic abnormalities we correlated the severity of renal and hepatic histological lesions to the type of PKHD1 mutations in 54 fetuses (medical pregnancy termination) and 20 neonates who died shortly after birth. Within this cohort, 55.5% of the mutations truncated fibrocystin. The severity of cortical collecting duct dilatations, cortical tubule and glomerular lesions, and renal cortical and hepatic portal fibrosis increased with gestational age. Severe genotypes, defined by two truncating mutations, were more frequent in patients of less than 30 weeks gestation compared to older fetuses and neonates. When adjusted to gestational age, the extension of collecting duct dilatation into the cortex and cortical tubule lesions, but not portal fibrosis, was more prevalent in patients with severe than in those with a non-severe genotype. Our results show the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease. Their absence, however, does not guarantee survival to the neonatal period.

Predictive factors of the response to chemoradiotherapy in esophageal cancer.

BACKGROUND: The aim of this study was to identify factors predictive of a complete endoscopic/histopathological response to chemoradiotherapy in patients with esophageal cancer. PATIENTS: Clinical and histopathological factors (Ki67, p53 and EGFR expression) were studied in 56 patients presenting with esophageal cancer between September 2000 and March 2006 (35 squamous cell carcinomas, 20 adenocarcinomas, one undifferentiated carcinoma). The response to chemoradiotherapy was evaluated endoscopically and by histological examination in 16 patients who underwent surgical resection. RESULTS: Independent factors predictive of a complete endoscopic response were good performance status (RR=15.75; CI: 1.74-142.58; P=0.01) and overexpression of Ki67 (RR=4.46; CI: 1.08-18.31; P=0.04). In patients who underwent surgery, a major histopathological response was associated with complete endoscopic response (P<0.01), complete CT-scan response (P=0.04) and good performance status (WHO=0) (P=0.04). The mean survival was 40 months. Adenocarcinoma histology (RR=3.18, CI: 1.13-8.54; P=0.02) and an impaired performance status (RR=4.79; CI: 1.07-21.41; P=0.04) were independently associated with poor survival. CONCLUSION: In the present study, good performance status and overexpression of Ki67 were two independent factors for complete endoscopic response after chemoradiotherapy for esophageal cancer. Independent risk factors for poor survival were adenocarcinoma histological type and impaired performance status. Further prospective studies are necessary to complete the present results.

Molecular heterogeneity in fetal forms of type II lissencephaly.

Type II lissencephaly (type II LIS) is a group of autosomal recessive congenital muscular dystrophies (CMD) associated with defects in alpha-DG O-glycosylation, which comprises Walker-Warburg syndrome, Fukuyama cerebral and muscular dystrophy, or muscle-eye-brain disease. The most severe forms of these diseases often have a fetal presentation and lead to a pregnancy termination. We report here the first molecular study on fetal type II LIS in a series of 47 fetuses from 41 unrelated families. Sequencing of the different genes known to be involved in alpha-DG O-glycosylation allowed the molecular diagnosis in 22 families: involvement of POMT1 was demonstrated in 32% of cases, whereas POMGNT1 and POMT2 were incriminated in 15% and in 7% of cases, respectively. We found 30 different mutations in these three genes, 25 were described herein for the first time, 15 in POMT1, and five in POMT2 and POMGNT1. Despite sequencing of FKRP, FCMD, and LARGE, no definitive molecular diagnosis could be made for the other half of our cases. Preliminary results concerning genotype-phenotype correlations show that the choice of the first gene sequenced should depend on the clinical severity of the type II LIS; POMT1 and POMT2 for severest clinical picture and POMGNT1 for milder disease. The other genes, FKRP, FCMD, and LARGE, seem not to be implicated in the fetal form of CMD.

[Linear insertion of the atrioventricular valves without defect]. / Insertion linéaire des valves atrioventriculaires sans défect. A propos d'une nouvelle série anatomique de 213 coeurs de foetus trisomiques 21.

On a first anatomical series of 52 hearts of trisomic 21 fetuses, published in June 2002, we described a new minor cardiac anomaly, belonging to the atrioventricular septal defect, with a linear insertion of the atrioventricular valves without defect. We want to confirm these data, on a larger series of 213 new hearts of trisomic 21 fetuses by adding a complementary section to the standard examination; 100% of controls have shown a normal insertion with an offsetting of the atrioventricular valves. On 113 out of these 213 hearts of trisomic 21 fetuses, with a so called "normal" heart at the standard examination showing no defect, the complementary section has shown that only 37.2% of these hearts have a normal insertion, whereas 62.83% show a linear insertion, without offsetting and without any septal defect. This linear insertion has been observed in all the different types of atrioventricular septal defect as a good hallmark for trisomy 21; but, since then, they have always been described associated with a septal defect, atrial or ventricular. Our hypothesis is that the linear insertion of the atrioventricular valves without defect is the minor form of the atrioventricular septal defect spectrum, taking place between the prior described partial types of atrioventricular septal defect, in which there is always a defect (ostium primum type atrial septal defect or inflow type ventricular septal defect), and the real normal heart. A precise description of the level of the complementary section and of the anatomic peculiarities of the linear insertion of the atrioventricular valves without defect would help its screening in fetal ultrasonography.

Value of fetal autopsy after medical termination of pregnancy.

We carried out a retrospective study of 352 medical terminations of pregnancy (MTP) carried out in a large French administrative region over two consecutive years. We analysed the indications for MTP and then compared the prenatal ultrasound diagnosis with fetal autopsy findings in order to demonstrate the value of pathological examination of the fetus in prenatal diagnosis and genetic counselling as well as the need to check by autopsy the quality of ultrasound screening. Preliminary analysis of the indication for these MTP showed that in 69.9% ultrasound screening had been carried out, revealing mainly brain abnormalities (22.2%) and heart defects generally associated with chromosomal abnormalities (32.1%). Prenatal findings were in agreement with autopsy results, showing no false-positive prenatal diagnoses. However, in 7.9% of cases in which brain abnormalities were detected, confirmation was not possible at autopsy because of tissue autolysis, showing the need for optimal conditions of expulsion. In 35.8% of cases, confirmation of the diagnosis by autopsy was not useful for management but still added to medical knowledge and demonstrated to the mother the reality of the defects. In 50.9%, the autopsy findings were decisive for genetic counselling.

Congenital atrioventricular block: histological aspects.

It is known that maternal immunological factors such as systemic disease are involved in the genesis of cardiac conduction problems in the fetus but the histologic changes in the conduction system are less documented. We report the case of a 33-year-old woman with no significant medical history. Her first pregnancy was induced by Clomifene. At 17 weeks of gestation, the fetus presented sonographic abnormalities characteristic of a complete atrioventricular block. Biological investigations found anti-SSA and -SSB antibodies. Clinical history search for systemic disease was positive for photosensitivity, lasting 10 years, suggesting the diagnosis of systemic lupus erythematosus. The patient was treated with prednisone 20 mg per day but fetal death occurred at 29 weeks of gestation. Histological examination of the fetal heart showed an altered atrioventricular node and bundle of His with fibrosis, calcifications, endocardial fibroelastosis and mononucleated inflammatory cells. The search for these specific lesions can be determinant in establishing the disease pathogenesis; also, it is important to eliminate this diagnosis in an unexplained fetal death.

[Outcome of infants with hypoplastic left heart syndrome diagnosed in utero]. / Devenir des enfants atteints d'une hypoplasie du coeur gauche diagnostiquée in utero.

The authors report the results of prenatal diagnosis of the hypoplastic left heart syndrome since 1998 in the University Hospitals of Marseille and Montpellier. Twenty-four prenatal diagnoses of this condition were made in mothers with a mean age of 29 (18 to 40 years) and after a mean term of 22 (18.5 to 33) weeks of amenorrhea. Seventeen therapeutic abortions were carried out and 7 neonates born after a mean term of 39 (28 to 40) weeks, were admitted to the paediatric intensive care unit. Two patients required ventilatory assistance with one early death. The other patients were stable after surgery. A Norwood (first stage) procedure was carried out in 6 neonates at a mean age of 5 (1 to 6) days. There was only one survivor (17%). Prenatal diagnosis of the hypoplastic left heart syndrome allows cardiac and extracardiac evaluation of foetuses with this condition. Therapeutic abortions may be proposed and was the commonest choice of the parents in this study. On the other hand, despite better management of neonates with this prenatal diagnosis, the poor prognosis of the Norwood first stage procedure is unchanged. A systematic search for a restriction of the foramen ovale on foetal echocardiography could optimise neonatal management of this problem.

Linear insertion of atrioventricular valves without septal defect: a new anatomical landmark for Down's syndrome?

Our objective was to explore whether minor anatomical abnormalities of the septal insertion of tricuspid and mitral valves could be a feature of trisomy 21 in fetuses with an otherwise normal heart. Postmortem examinations were performed in 41 fetuses affected by Down's syndrome and in 52 controls. Adjoining the standard postmortem procedure, an apex-to-base section of the crux of the heart was made on a plane corresponding to the sonographic four-chamber view. This allowed gross and histological examination of the hinge points of tricuspid and mitral leaflets, showing the usual apical displacement of the tricuspid valve in all controls. Of 41 fetuses affected by Down's syndrome, 18 had a structural heart defect. Of the 23 Down syndrome fetuses without a patent heart defect, 16 (i.e., 69% of those considered as having 'normal hearts') had nevertheless a linear insertion of atrioventricular valves at autopsy. Prospective clinical studies are required to evaluate if these postmortem findings can be transposed to the clinical setting of 2nd-trimester sonographic screening.

Congenital disseminated malignant rhabdoid tumor and cerebellar tumor mimicking medulloblastoma in monozygotic twins: pathologic and molecular diagnosis.

Malignant rhabdoid tumors are highly aggressive childhood tumors. Recently, all of the malignant rhabdoid tumors, whatever their location, have been related to the inactivation of the hSNF5/INI1 gene. A subset of cerebral tumors, associated with malignant rhabdoid tumors or isolated ones arising in siblings, showed similar molecular alterations. We report for the first time in monozygotic twins a congenital disseminated malignant rhabdoid tumor in one twin and a cerebellar tumor mimicking a medulloblastoma in the other. Molecular analysis revealed similar alterations for both tumors: a deletion of exon 7 of the hSNF5/INI1 gene in one allele, and a point mutation in the same exon in the other, suggesting a common genetic pathway. Analysis of constitutional DNA revealed a germline mutation. These findings are in favor of a common etiology for rhabdoid tumor and a subset of brain tumors developing in infancy.

[Crohn's disease and small intestine adenocarcinoma]. / Maladie de Crohn et adénocarcinome du grêle.

INTRODUCTION: The relationship between digestive neoplasia and Crohn's disease remains debated but several cases of carcinoma have been reported in the past 10 years. EXEGESIS: We report two cases of intestinal adenocarcinoma found in young people. Patients were asymptomatic during 15 years after the diagnosis of inflammatory bowel disease and presented a sudden occlusive syndrome. Carcinoma was observed incidentally at gross examination, and histopathological study showed dysplasia adjacent to neoplasia. Despite adequate surgical resection, death occurred quickly. CONCLUSION: Crohn's carcinoma should be suspected in patients with long-standing disease, poor symptomatology, and stenosis. Intestinoscopy surveillance remains illusory because inflammatory stenosis is often present and infiltrative neoplasia is invisible. Thus, it is important to be vigilant in this clinical presentation.

[Value of cytokeratin 7 and 20 for the diagnosis of cerebral metastases of adenocarcinoma: study of 78 cases]. / Intérêt des cytokératines 7 et 20 pour le diagnostic des métastases cérébrales d'adénocarcinome: étude de 78 cas.

OBJECTIVE: histological features of metastasis are not always specific of the origin. The usefulness of cytokeratin 7 and 20 (CK7 and CK20) in cerebral metastases from an adenocarcinoma was studied in a series of 78 patients. RESULTS: metastases from lung adenocarcinoma showed a CK7+/CK20- pattern in 79% of cases, CK7+/CK20+ in 19% and CK7-/CK20- in 2%. When observed, positivity for cytokeratin 20 was generally focal or weak. Breast adenocarcinoma metastases were CK7+/CK20- in 71% of cases and CK7-/CK20- in 29%. Less differentiated tumours were usually negative for both cytokeratins. Metastases by colonic adenocarcinoma were CK7-/CK20+ in 100% of cases. Cytokeratins 7 and 20 are useful to distinguish lung from colonic metastatic carcinoma. In case of double positivity, a more intense CK7 expression is rather suggestive of a lung origin. CONCLUSION: these results might modify paraclinic investigations in search of the primitive tumor.

[Contribution of immunohistochemistry and electron microscopy for the diagnosis of meningeal hemangiopericytomas. 15 case reports]. / Apport de l'immunohistochimie et de la microscopie électronique dans le diagnostic des hémangiopéricytomes méningés. A propos de 15 cas.

Meningeal hemangiopericytomas (HPC) are rare CNS tumors with a pour prognosis compared to meningiomas. In order to define diagnosis criteria, we performed an immunohistochemical and ultrastructural study in respectively 15 and 5 meningeal HPC. The following antibodies anti-KL1, EMA, vimentin, CD34, factor VIII, alpha-smooth actin, estrogen and progesteron receptors (RE, RP) were used in paraffin embedded sections whereas anti-NCAM and E-cadherin antibodies were used on frozen sections when available. We can differentiate meningeal HPC from meningioma because of a complete lack of immunostaining with epithelial markers as well as with NCAM antibody or RE and RP receptors. Besides a positivity with CD34 and alpha-smooth actin antibodies was always observed even focally in HPC. On the other hand, solitary fibrous tumor showed a strong and diffuse positivity with anti CD34 and anti-vimentin antibodies. Electron microscopy can be helpful in some instances showing membrane basal-like substance and absence of desmosomes.

[Value of endocervical margin examination of conization specimens. Prospective study conducted on 150 patients]. / Intérêt de l'examen extemporané de la limite supérieure d'exérèse des pièces de conisation. Etude prospective portant sur 150 patientes.

OBJECTIVE: To assess the usefulness of frozen sections (FS) on endocervical margin in surgical conization or loop electrosurgical specimens. MATERIAL AND METHODS: In a prospective study, 150 patients were treated from October 1995 to December 1997: 69 cases without FS, 81 cases with FS. CIN on frozen section resulted in an immediate additional resection. RESULTS: In the group without FS, 13 patients had involved endocervical margin by high-grade CIN (18.8%). Frozen section was impossible in a conization specimen that was too short. FS revealed 64 normal glandular epitheliums, seven squamous metaplasias in which two lesions were under-evaluated (being in fact CIN on permanent sections), eight high-grade CIN followed by additional resection in six cases and two invasive carcinomas. Endocervical margin on additionals section were always free of disease. The rate of failure was 2.6% among 77 cases. This rate corresponded to two under-evaluations. Invasive carcinoma and CIN without additional resection were excluded because frozen section only allowed a peroperative diagnosis. The average height of the cone and the rate of complications were similar. Repeat surgery was necessary in nine cases in the group without frozen section, in which five showed residual lesions, absent in the other group. CONCLUSION: The ultimate histological interpretation was never difficult after frozen section. This method permits reduction of cases with involved cone margin and residual lesions and, despite some limitations, it may be useful for surgical management.

Immunohistochemical localization of cytokines, C5b-9 and ICAM-1 in peripheral nerve of Guillain-Barré syndrome.

The spectrum of the Guillain-Barré Syndrome (GBS) has recently been widened by the newly identified forms of acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN). An important question has been raised regarding the possibility for the axon to be a target in immune-mediated damage. Although myelin breakdown is the characteristic feature of classic acute inflammatory demyelinating polyradiculoneuropathy (AIDP), axonal degeneration may occasionally be observed in this form, especially in cases with explosive onset and severe clinical course. Immunohistochemical findings of five frozen sural nerves biopsies of patients with GBS (AIDP variant) tested with a panel of monoclonal antibodies raised against different molecules implicated in immune-mediated processes have principally disclosed an immunoreactivity of tumor necrosis factor-alpha (TNF-alpha) on both Schwann cell membranes and in myelinated and unmyelinated axons. On the other hand, interleukin 1-beta (IL1-beta) labeled Schwann cells, endothelial cells and macrophages; interferon-gamma (IFN-gamma) was observed both in endothelial cells and lymphocytes. Membrane attack complex (C5b-9) deposits were observed on Schwann cell membranes and finally intercellular adhesion molecule-1 (ICAM-1) was localized both on endothelial cells and macrophages. Our findings strongly suggest that TNF-alpha is an important factor in the cascade of events leading to immune-mediated demyelination and axonal damage in GBS.

Local expression of monocyte chemoattractant protein-1 (MCP-1) in idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM), are a group of autoimmune diseases characterized by the recruitment of lymphocytes and monocytes to the site of affection. The mechanism for recruitment of these cells likely involves chemokines. The monocyte chemoattractant protein-1 (MCP-1), a chemoattractant to T lymphocytes and monocytes, may play an important role in the pathogenesis of IIM. Frozen muscular tissues were obtained from eight cases of DM, five PM, and four IBM. We investigated the MCP-1 expression by the reverse transcription-PCR technique, immunohistochemistry and in situ hybridization. MCP-1 mRNA was markedly expressed in all the IIM cases. Greater amounts of MCP-1 mRNA were observed in DM, and in situ hybridization showed MCP-1 mRNA accumulation in perivascular mononuclear cells. Immunohistochemistry showed MCP-1 expression in vessels (endothelial cells and walls of veins and arteries) in all IIM cases. Very few mononuclear cells in DM perivascular infiltrates expressed MCP-1, whereas in PM and IBM, it was strongly expressed by mononuclear cells partially invading non-necrotic muscle fibers. These findings suggest that MCP-1 can contribute to the inflammatory response by attracting monocytes and T lymphocytes to sites of cell-mediated immune injury. The morphological characteristics and distribution of positive cells indicate that macrophages, lymphocytes, and endothelial cells previously reported to produce MCP-1, contribute to its production in IIM lesions.