The impact of the COVID-19 pandemic on the use of Emergency Departments in Italy.

Background: During 2020, COVID-19 had a diversified distribution in Italy, the first nation in Europe to experience the outbreak of the epidemic. This was linked to geographical differences in population density and distribution of healthcare facilities, including Emergency Departments (EDs). This study aims to assess the impact of the pandemic on ED utilization in 2020 across different subpopulations and geographical locations in Italy. Methods: We used anonymized data from a survey conducted by the Italian National Institute of Statistics on 25,000 families to analyze the yearly rate of people who used EDs from 2015 to 2020. The rate of persons who accessed ED services in 2020 per 1,000 population was compared with those of the previous non-pandemic years. Results: The number of people accessing EDs in 2020 was 32.3% lower, although this reduction was not uniform across the 21 regions / autonomous provinces. People aged 0-14 years experienced the highest reduction in ED visits. In 2020, low educational level people exhibited a steeper reduction in the use of EDs. Conclusions: This study shows a significant drop in EDs use especially by children; the population section mostly affected by the effects of the pandemic. This study also confirms that education and socio-economic status are important determinants of ED use. The heterogeneous reduction in ED use across the regions of Italy highlights the need to further investigate the impact of this pattern on the health of the population, as well as to define adequate preparedness strategies to face future emergencies.

MR Brain Screening in ADPKD Patients : To Screen or not to Screen?

BACKGROUND: Adult polycystic kidney disease (ADPKD) still represents a major cause of renal failure and intracranial aneurisms (IA) have a higher prevalence in ADPKD than in the general population. Current guidelines suggest performing brain MRI only in the subjects with a positive familiar history of IAs or subarachnoid hemorrhage (SAH). This is a retrospective case-control analysis to evaluate the usefulness of a MR screening program in ADPKD patients. METHODS: We retrospectively analyzed all ADPKD patients followed in our outpatient clinic between 2016 and 2019 who underwent a brain MRI screening. We evaluated the presence of IAs and others brain abnormalities and compared our results with a non-ADPKD population (n = 300). We performed univariate and multivariate regression analysis to evaluate if general and demographic features, laboratory findings, clinical parameters and genetic test results correlated with IAs or other brain abnormalities presence. RESULTS: Among the patients evaluated 17 out of 156 (13.6%) ADPKD patients had IAs, compared to 16 out of 300 (5.3%) non-ADPKD controls (p < 0.005). Considering ADPKD patients presenting IAs, 12 (70.6%) had no family history for IAs or SAH. Genetic analysis was available for 97 patients: in the sub-population with IAs, 13 (76.5%) presented a PKD1 mutation and none a PKD2 mutation. We found that arachnoid cysts (AC) (p < 0.001) and arterial anatomical variants (p < 0.04) were significantly more frequent in ADPKD patients. CONCLUSION: In our population ADPKD patients showed a higher prevalence of IAs, AC and arterial variants compared to non-ADPKD. Most of the IAs were found in patients presenting a PKD1 mutation. We found a significant number of alterations even in those patients without a family history of IAs or SAH. The practice of submitting only patients with familial IAs or kidney transplantation candidates to MRI scan should be re-evaluated.

Trust of Italian healthcare professionals in COVID-19 (anti-SARS-COV-2) vaccination.

ABSTRACT: Background. Vaccination is one of the most effective tools available to Public Health. Its potential usefulness is threatened by the rise of vaccine hesitancy among the general population, which has grown as much as to prompt the World Health Organization to express its concerns on the matter. The risk posed by vaccine hesitancy is even more concerning in the light of the efforts to curb the ongoing COVID-19 pandemic, which focus mainly on mass vaccination campaigns. This holds especially true when applied to healthcare professionals, among whom vaccine hesitancy can be particularly detrimental. For these reasons, our study focuses on potential determinants of vaccine hesitancy among healthcare professionals. Study design. The study is a cross-sectional study. Methods. Data were collected from January 1st to February 16th, by means of a self-administered online questionnaire in a cohort of Italian healthcare professionals. Results. Overall, 10,898 questionnaires were collected. Among the respondents, 1.1% expressed vaccine hesitancy. Hesitancy was less frequent in professionals involved in Primary Care and in the Clinical Scien-ces/Public Health group. Among clinicians, paediatricians, oncologists, and geriatrists showed especially accepting attitudes towards vaccination. Lower hesitancy rates were also registered among the respondents who already had received influenza vaccination and who never had any adverse effects following vaccination. Higher hesitancy rates were observed among individuals who had family members aged >65 years and with a history of severe adverse reactions to vaccination. Conclusion. Vaccine hesitancy rates were extremely low among participants in our study. Some medical specialties shown were particularly accepting towards vaccination. The potential predictors and protective factors pointed out by our analysis might allow more refined targets.

COVID-19 Vaccine Hesitancy and Early Adverse Events Reported in a Cohort of 7,881 Italian Physicians.

Background: The COVID-19 vaccination campaign began in Italy at the end of December 2020, with the primary aim of immunizing healthcare professionals, using the EMA approved mRNA vaccines (Comirnaty® by Pfizer/BioNTech; mRNA-1273 by Moderna) and recombinant adenoviral vaccine (Vaxzevria® by AstraZeneca). The study aimed at evaluating the prevalence and motivations underlying Vaccine Hesitancy, as well as the incidence and type of adverse events associated with COVID-19 vaccination. Methods: Cross-sectional study. Data were collected January 1st to 28th 2021 using a purposely created online self-administered questionnaire from a selected cohort of Italian physicians. Results: Overall, 7,881 questionnaires were analyzed: 6,612 physicians had received one dose, and 1,670 two doses of Comirnaty®; 30 had received one dose of mRNA-1273. Vaccine Hesitancy rate was 3.6%; it correlated with prior SARS-CoV-2 infection, diabetes, Adverse Eventss at previous vaccinations and refusal of 2020 flu vaccine, and was mainly motivated by concerns about vaccine Adverse Events. Typical Adverse Events were pain/itching/paresthesia at the inoculation site, followed by headache, fever, fatigue and myalgia/arthralgia occurring more frequently after the second dose (77.8 vs 66.9%; p<0.001), and in subjects with a prior SARS-CoV-2 infection. Conclusion: Adherence to COVID-19 vaccination is high among physicians. Adverse Events are typically mild and more frequent in people with a prior SARS-CoV-2 infection.

Measures of walkability in the pediatric population: a qualitative review of the literature.

CONTEXT: Sedentary lifestyle is spreading among children living in urban settings. Recent studies in urban health investigated the effects of built environment on children's physical activity, focusing on the concept of "walkability", an index of how much an area is conducive to walking and active transportation. We decided to browse the literature in order to review all possible tools and methods by which walkability has been evaluated and measured. METHODS: We conducted a qualitative review of the literature in agreement with PRISMA guidelines, searching three medical databases for papers published between January 1994 and July 2017. Inclusion criteria were: primary studies, population ≤18 years and exposure variable as an assessment of walkability or built environment. RESULTS: We retrieved 1,702 articles and included 195 of them in the final review. Most of the studies were cross-sectional (n=188, 96.4%). We identified two possible approaches and four main tools to address walkability measurement. A subjective method approach was used in 71 studies (36.4%), an objective method in 87 (44.6%). Only 37 studies (19.0%) used both. Main tools were survey (n=70, 35.9%), Geographic Information System (GIS) (n=64, 32.8%), street audits (n=11, 5.6%) and Walk-score™ (n=3, 1.5%). Forty-six studies (23.4%) used mixed methods. Environmental variables' assessment and definition was found to vary greatly by method of choice. CONCLUSIONS: We found a high degree of heterogeneity regarding methods and measurements of walkability. A standard approach regarding tools and environmental variables' choice and definition will be advisable in order to allow comparisons among studies. Also, more longitudinal studies are needed.

Results and predictors of outcome of endoscopic endonasal surgery in Cushing's disease: 20-year experience of an Italian referral Pituitary Center.

PURPOSE: To assess outcomes and predictors of early and long-term remission in patients with Cushing's disease (CD) due to ACTH-secreting adenomas treated via endoscopic endonasal approach (EEA). METHODS: This is a retrospective study. Consecutive patients operated for CD from 1998 to 2017 in an Italian referral Pituitary Center were enrolled. Clinical, radiological, and histological data at enrollment and follow-up were collected. RESULTS: 151 patients (107 F) were included; 88.7% were naïve for treatment, 11.3% had been treated surgically and 11.2% medically. At pre-operative magnetic resonance imaging (MRI), 35 had a macroadenoma and 80 a microadenoma, while tumor was undetectable in 36 patients. Mean age at surgery was 41.1 ± 16.6 years. Diagnosis was confirmed histologically in 82.4% of the cases. Patients with disease persistence underwent second surgery and/or medical and/or radiation therapy. Mean follow-up was 92.3 ± 12.0 (range 12-237.4) and median 88.2 months. Remission rate was 88.1% after the first surgery and 90.7% at last follow-up. One patient died of pituitary carcinoma. Post-surgical cortisol drop (p = 0.004), tumor detection at MRI (p = 0.03) and size < 1 cm (p = 0.045) increased the chance of disease remission; cavernous sinus invasion was a negative predictor of outcome (p = 0.002). Twenty-seven patients developed diabetes insipidus and 18 hypopituitarism. Surgery repetition increased the risk of hypopituitarism (p = 0.03), but not of other complications, which included epistaxis (N = 2), cerebrospinal fluid leakage (1), pneumonia (3), myocardial infarction (1), and pulmonary embolisms (2). CONCLUSIONS: Selective adenomectomy via EEA performed by experienced surgeons, supported by a multidisciplinary dedicated team, allows long-term remission in the vast majority of CD patients with low complication rate.

Comparative assessment of hypothalamic-pituitary-adrenal axis suppression secondary to intrabursal injection of different glucocorticoids: a pilot study.

BACKGROUND: Hypothalamic-pituitary-adrenal axis (HPAA) suppression is the most common and dangerous, although often unrecognized and untreated, side effect of glucocorticoid administration. The risk and duration depend both on patient and treatment characteristics. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) currently represents the gold standard method to evaluate the metabolism of endogenous and exogenous steroids. OBJECTIVE: To assess prevalence, severity, and duration of HPAA suppression subsequent to the injection of two steroids with equivalent potency but different pharmacokinetics. SUBJECTS AND METHODS: Single-blind randomized case-control pilot study. Forty patients (22 F; age 48.7 ± 7.2 years) with shoulder calcific tendinopathy received an intrabursal injection of 40 mg of 6α-methylprednisolone acetate (MA) or triamcinolone acetonide (TA). Just before (T0) and after 1 (T1), 7 (T2), 15 (T3), 30 (T4) and 45 (T5) days, we assessed morning blood cortisol and ACTH by RIA, and 24-h urinary levels of MA, TA and free cortisol by HPLC-MS/MS. RESULTS: HPAA function was normal at baseline. At T1, all patients presented HPAA suppression reaching the lowest cortisol, ACTH and UFC levels, that were similar between groups. At T2, mean cortisol remained lower than at baseline (p < 0.0001) in the TA group. In both groups, mean cortisol and ACTH levels progressively normalized, suggesting HPA recovery, except for three patients in the MA and two in the TA group. UFC levels remained lower than normal (p < 0.0001) up to T5, despite the disappearance of exogenous GCs. No patient developed manifestations of hypocortisolism. CONCLUSIONS: A single 40-mg intrabursal injection of MA or TA is sufficient to suppresses HPAA up to 45 days. Although typically asymptomatic, patients should be instructed to recognize and report symptoms suggestive for hypocortisolism, to provide prompt diagnosis, and eventually, treatment, thus avoiding severe complications.

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution.

PURPOSE: Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors. METHODS: 52 patients (30 F; age 61 ± 13 years) with advanced melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2 weeks) or pembrolizumab (2 mg/kg i.v./3 weeks). Thyroid function and autoimmunity were assessed before, after 6 weeks, at the end of ipilimumab, as well as before and every 3 months during nivolumab/pembrolizumab treatment. RESULTS: During ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1 associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7 patients (3 F) developed hypothyroidism with severe manifestations in 6 of them; 3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean follow-up after anti-CTLA4 inhibitors treatment was 36 ± 28 months. Thyroid disorders occurred 45.1 ± 20.8 and 151 ± 67 days after the initiation of CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation were associated with a better clinical response to CTLA4 followed by PD1 treatment. CONCLUSIONS: Immune checkpoint blockade is burdened by a high incidence of autoimmune thyroid dysfunction, which is often severe. Therefore, early and careful monitoring and, eventually, treatment are crucial to prevent the negative impact of thyroid dysfunction on the clinical outcome.

Effectiveness of educational and lifestyle interventions to prevent paediatric obesity: systematic review and meta-analyses of randomized and non-randomized controlled trials.

OBJECTIVE: This review and meta-analysis aim at updating a previous meta-analysis carried out by Waters et al. on the efficacy of interventions aimed at preventing childhood obesity and at identifying predictors of outcome. METHODS: Using an ad-hoc search string, PubMed database was searched for studies assessing body mass index reduction associated with programmes lasting ≥12 weeks in overweight and obese children aged 2-18 years. Studies designed for children with eating disorders or relevant comorbidities were excluded. Studies meeting inclusion criteria were classified according to patient age (<6, 6-12 and 13-18 years), and intervention type (physical activity, diet or both), setting (educational, family or both) and duration (≤1 or >1 year). The search was also extended to other databases. Hand-searching techniques were also applied. The Cochrane 'risk of bias' was applied for quality assessment. RESULTS: Seventy-two studies were meta-analysed. Overall, the best results were achieved by programmes combining diet and physical activity (n = 39). With regard to the setting, programmes involving both school and family and lasting ≤1 year were the most efficacious for 6- to 12-year-old children (n = 26); family-based-only interventions were also effective in children <6 years old (n = 2), although results have to be interpreted cautiously because of the small number of patients enrolled and the high study heterogeneity. In 13- to 18-year-old patients, interventions delivered at school (n = 8) were substantially unsuccessful. CONCLUSIONS: Interventions for childhood obesity prevention should include both diet and physical activity, be preferentially targeted towards school age children and involve both the school and family setting. However, because of the important methodological limitations associated with currently available literature, additional studies are needed to draw definite conclusions.

Usefulness of an ad hoc questionnaire (Acro-CQ) for the systematic assessment of acromegaly comorbidities at diagnosis and their management at follow-up.

PURPOSE: To determine the validity of a self-administered questionnaire (Acro-CQ) developed to systematically assess the presence, type and time of onset of acromegaly comorbidities. METHODS: This is a cross-sectional study; 105 acromegaly patients and 147 controls with other types of pituitary adenoma, referred to a specialized Italian Center, autonomously compiled Acro-CQ in an outpatient clinical setting. To test its reliability in a different setting, Acro-CQ was administered via mail to 78 patients with acromegaly and 100 with other pituitary adenomas, referred to a specialized US Center. Data obtained from questionnaires in both settings were compared with medical records (gold standard). RESULTS: Demographics of patients and controls from both countries were similar. In both settings, >95 % of the questionnaires were completely filled; only one item was missed in the others. Concordance with medical record was excellent (k > 0.85) for most of the items, independently from the way of administration, patient age, gender and nationality, pituitary adenoma type and disease activity. CONCLUSIONS: Acro-CQ is an inexpensive, highly accepted from patients and reliable tool recommended to expedite systematic collection of relevant clinical data in acromegaly at diagnosis, to be replicated at follow-ups. This tool may guide a targeted, cost-effective management of complications. Moreover, it could be applied to retrieve data for survey studies in both acromegaly and other pituitary adenomas, as information is easily and rapidly accessible for statistical analysis.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Probiotics for prevention of atopic diseases in infants: systematic review and meta-analysis.

Growing evidence underlines the pivotal role of infant gut colonization in the development of the immune system. The possibility to modify gut colonization through probiotic supplementation in childhood might prevent atopic diseases. The aim of the present systematic review and meta-analysis was to evaluate the effect of probiotic supplementation during pregnancy and early infancy in preventing atopic diseases. PubMed, Embase and Cochrane Library were searched for randomized controlled trials evaluating the use of probiotics during pregnancy or early infancy for prevention of allergic diseases. Fixed-effect models were used, and random-effects models where significant heterogeneity was present. Results were expressed as risk ratio (RR) with 95% confidence interval (CI). Seventeen studies, reporting data from 4755 children (2381 in the probiotic group and 2374 in the control group), were included in the meta-analysis. Infants treated with probiotics had a significantly lower RR for eczema compared to controls (RR 0.78 [95% CI: 0.69-0.89], P = 0.0003), especially those supplemented with a mixture of probiotics (RR 0.54 [95% CI: 0.43-0.68], P < 0.00001). No significant difference in terms of prevention of asthma (RR 0.99 [95% CI: 0.77-1.27], P = 0.95), wheezing (RR 1.02 [95% CI: 0.89-1.17], P = 0.76) or rhinoconjunctivitis (RR 0.91 [95% CI: 0.67-1.23], P = 0.53) was documented. The results of the present meta-analysis show that probiotic supplementation prevents infantile eczema, thus suggesting a new potential indication for probiotic use in pregnancy and infancy.

[Stromal tumors of the small intestine (GIST). Prognostic differences based on clinical, morphological and immunophenotypic features]. / I tumori stromali del piccolo intestino (GIST). Differenze prognostiche sulla base delle caratteristiche cliniche, morfologiche e immunofenotipiche.

Gastro Intestinal Stromal Tumors (GIST) are rare malignant non-epithelial tumors arising from gastro-intestinal tract. They represent the 0.2% of all malignancy of this site. Three cases, treated in our Department, are an example of the anatomo-clinical features of these tumors. In two cases the clinical features on admission were similar to those of acute abdominal pain; in the third one a palpable mass rapidly growing was observed. All three patients had surgical treatment but survival were quite different. The size of tumor mass in the first two cases was 5 cm; one patient was alive after ten years without relapse, the second one died five years after with liver metastasis. The third one, with a mass larger more than ten centimeters, developed 8 months after surgical resection a diffuse local relapse of the disease. The microscopic pattern and the lack of epithelial markers allowed to classify them as GIST. All cases were tested with S100 protein, smooth muscle actine, and CD-34 antigen. Two cases had both smooth muscle and nervous markers, the third resembled a malignant schwannoma. Prognosis was correlated with the size of tumor at the time of surgery and immunophenotype pattern. The tumors with high expression of nervous antigens had a worse prognosis.

Effusion cytology of hepatocellular carcinoma.

OBJECTIVE: To evaluate effusion cytology on routine smears in patients with hepatocellular carcinoma. STUDY DESIGN: Filed smears from 106 patients with autopsy-proven hepatocellular carcinoma were retrospectively reviewed for the presence of malignant cells. Morphologic patterns, as well as immunochemical reactivity for a panel of antibodies, were analyzed when feasible. RESULTS: Malignant cells were identified in 10 cases of ascites and 1 of pleural fluid. Positive smears were variably cellular, with paucicellular, round or linear aggregates of polygonal cells. The cytoplasm was usually evident and very stainable. The nuclei were hyperchromatic or vesicular, with inconspicuous nucleoli. Reactive changes were frequent. Malignant cells were positive for keratins (7/8) and erythropoietin (4/8) and negative for carcinoembryonic antigen (0/8). Concomitant cirrhosis was present in 103 cases (97.1%); all the noncirrhotic cases had malignant cells identifiable in the effusion. Antemortem clinical diagnosis of malignancy was made in 59 cases (55.7%); cytology was the only source of the morphologic diagnosis in most of them. CONCLUSION: These results indicate that although the yield of hepatocellular carcinoma in effusion cytology is limited, it may be important in the initial assessment of the disease, given the ineligibility of most patients for invasive procedures and the equivocal features of instrumental investigations. Immunocytochemistry may further assist in differentiating doubtful cases.

Interictal abnormalities of regional cerebral blood flow in migraine with and without aura.

Some controversial issues exist whether regional cerebral blood flow (rCBF) changes are present both in migraine with and without aura during the interictal period. For this reason we have studied rCBF characteristics in migraine patients when headache-free. rCBF examinations were performed by the 133Xe inhalation method on 39 normal subjects (24 aged 45 or less and 15 older than 45), on 10 migraine patients with (A+) and on 10 without (A-) aura. The values of each patient were compared with the age-matched control population mean by a computer-assisted mapping system that allows statistical analysis in real time. To compare inter-individual variability 10 subjects, out of 39 normals, constituted an age-, sex- and CO2-matched control group (C). 8 A+ patients and 7 A- showed significant alterations of CBF in comparison with the age-matched control population. The analysis between the age-, sex- and CO2 matched groups showed significant differences of the inter-hemispheric (F = 6.669, p = 0.004) and of the frontal (F = 7.480 p = 0.0008) asymmetries. These data show that in the headache-free period a derangement of the cerebral perfusion is present in both migraine with and without aura, suggesting they are due to the same disease process. Furthermore they show the usefulness of a computer-assisted mapping system, suitable for clinical use, in discovering small alterations in cerebral perfusion.

Multicentric papillomavirus infection of the female genital tract. A study of morphologic pattern, possible risk factors and viral prevalence.

We have investigated 103 biopsy specimens obtained from 50 women (average 28.1 years, range 16-66) with multicentric condylomatosis of the genital tract, including the uterine cervix (48 samples), the vagina (23), and the vulva (32). Each patient had at least 2 biopsies. A positive in situ hybridization for a Human Papilloma Virus (HPV) cocktail was observed in samples from 38 patients: in these multiplicity of lesions regarded the cervix and vulva (22 cases), cervix and vagina (12), vulva and vagina (1), cervix, vulva and vagina (3). Viral types 6,11 were more prevalent in simple condylomata. Both low- and high grade lesions of cervix, vagina, and vulva showed prevalence of types 16, 18 and 31, 33, 35. Signaling for more than one probe cocktail was detected in 14 (13.6%) samples. Partner's condylomatosis was referred to by a sizeable minority of patients. It is concluded that the spectrum of HPV infection in the female genital tract reflects a multiplicity of factors, including involved viral type and site, immunitary reaction of the host, perpetration or reactivation of latent infections.

Association of breast cancer and meningioma. Report of 12 new cases and review of the literature.

We report 12 new cases of female breast cancer associated with intracranial meningiomas, inclusive of autopsy study. At the time of death the patients' age ranged from 52 to 95 years (average 70.6 years). Breast carcinomas were documented ante mortem in 11 cases and at autopsy in 1. Meningiomas were diagnosed at autopsy (10 cases) or in vivo (2 cases). The diagnosis of meningioma antedated that of mammary carcinoma in only one patient. Histologically, the cancers were of ductal (11 cases) and lobular infiltrating (1 case) types and showed a variable malignancy grade. Widespread extracranial metastases were present at autopsy in 7 cases. Brain metastases were seen in 1 case. Neurologic signs were referred in 4 subjects. Four breast cancers and one meningioma showed immunoreactivity for progesterone receptors, whereas all the cases were negative for estrogen receptors. In one case, metastatic breast carcinoma tissue was present within a psammomatous meningioma. A brief review of the literature, which includes 14 similar observations, is reported. Although the association of breast cancer and meningioma is still difficult to explain, its clinical implications are important and deserve proper attention. A proper work up in patients with suspected intracranial metastases is recommended so that resectable meningiomas are not mistaken for metastases.