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Introduction/Objectives: Due to the risks associated with sedative hypnotic medications in older adults, our study evaluated the impact of a multidisciplinary approach to deprescribing in geriatric primary care clinics. Methods: The study was a retrospective review of older adults at 2 academic, geriatric primary care clinics who were prescribed sedative-hypnotic medications. Patients were mailed an education packet of information that included working with the clinical pharmacy team, behavioral health team, or both in order to deprescribe their sedative-hypnotic medication. The study assessed the rate of discontinuation of sedative-hypnotic medications between the different intervention groups. Results: The study included 93 older adults with a mean age of 81.3 years and 39.8% discontinuation rate of their medication. The number of falls decreased in patients who discontinued use compared to when previously using a sedative hypnotic medication. Conclusion: Patients are more likely to discontinue their sedative hypnotic medication with a multidisciplinary approach, specifically with primary care provider support.

Background Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance—IR or diabetes mellitus—T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF. Methods Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D. Results Compared with EU and IR, T2D was associated with increased filling pressures (E/e′ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p 2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p 2 in the T2D group (+ 13% increase in RV dimension, − 21% decline in TAPSE/PAPS ratio and − 20% decrease in peak VO2). Conclusion The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis. Trial registration ClinicalTrials.gov identifier: NCT023358017

Athletes training is often associated with morphological changes in the heart. In this sense, the ventricular pressure-volume (PV) relation provides a complete characterization of cardiac pump performance. Regarding the arterial system (AS), arterial wall viscosity is a source of energy dissipation, that takes place during mechanical transduction. Left ventricular stroke work (SW) constitutes the useful fraction of ventricular energy that is delivered to the AS.Left ventricular PV-loops were evaluated in terms of AS viscous property, by means of the interaction of two SW components (Stroke Work Damping Ratio, SWDR), both in untrained and trained subjects.Fourteen healthy individuals (seven trained) were noninvasively evaluated in terms of echocardiographic and aortic pressure measurements.SWDR was observed to be increased in trained subjects.SWDR was evaluated in trained individuals, being increased in comparison with the non-trained group. This effect is a consequence of a significant increase of SWD, which could be related with the viscous mechanical property of AS.

Aims Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients. Methods and Results The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P Conclusion MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target. Trial registration ClinicalTrials.gov identifier: NCT023358017

To estimate the impact of a school-based nutritional and healthy lifestyle intervention to increase the proportions of adolescents free of components of the metabolic syndrome.We conducted a pre-experimental study in a representative sample of adolescents from two schools in a high Andean district of Peru (Cajamarca city); 388 students completed the intervention and the baseline and post-intervention measurement. The intervention had nine thematic modules; each module was developed in an educational session of 45 minutes every two weeks. We used the National Cholesterol Education Program Expert Panel and Adult Treatment Panel III criteria for metabolic syndrome. We used paired proportions comparison (McNemar test) to determine the impact of the intervention.At baseline, 20.4% (95% CI: 16.2 to 24.5) students had no metabolic syndrome components, post-intervention this proportion increased to 32,5% (95% CI: 27.7 to 37.3), the difference in proportions was 12.1% (95% CI: 7.5 to 16.8; p0.001). The prevalence of metabolic syndrome was 4.6% (95% CI: 2.4 to 6.9) at baseline, while post-intervention was 2.3% (95%CI: 0.7 to 3.9). During the analysis of components, the greatest reduction was observed in the proportion of hypertriglyceridemia (difference in proportions: 21.9%, 95%CI: 16.9 to 26.9, p0.001); we also found a significant reduction in arterial hypertension (difference in proportions: 3.1%, 95% CI: 0.6 to 5.6, p=0.025). In the other components, there were no significant differences.The school-based intervention increased in 59.3% the proportion of students free of any component of the metabolic syndrome.Estimar el efecto de una intervención educativa basada en nutrición y estilos de vida saludables para incrementar la proporción de adolescentes libres de componentes del síndrome metabólico.Se realizó un estudio preexperimental en una muestra representativa de adolescentes de dos escuelas de un distrito altoandino del Perú (ciudad de Cajamarca); 388 estudiantes completaron la intervención, así como la medición basal y la posintervención. La intervención tuvo nueve ejes temáticos, cada uno fue desarrollado en una sesión educativa de 45 min cada dos semanas. Se usó los criterios del National Cholesterol Education Program Expert Panel and Adult Treatment Panel III para el síndrome metabólico. Se realizó la comparación de proporciones pareadas (prueba de McNemar) para determinar el impacto de la intervención.En la medición basal, el 20,4% (IC95%: 16,2 a 24,5) no tenía componentes de SM, posintervención dicha proporción se incrementó a 32,5% (IC95%: 27,7 a 37,3), la diferencia de proporciones fue 12,1% (IC95%: 7,5 a 16,8; p0,001). La prevalencia de síndrome metabólico fue 4,6% (IC95%: 2,4 a 6,9) basalmente; posintervención fue 2,3% (IC95%: 0,7 a 3,9). La diferencia de proporciones fue 2,3%, (IC95%: 0,3 a 3,2; p=0,022). Entre los componentes, la mayor reducción fue en la proporción de hipertrigliceridemia (diferencia de proporciones: 21,9%, IC95%: 16,9 a 26,9; p0,001), también se observó una reducción significativa de la hipertensión arterial (diferencia de proporciones: 3,1%, IC95%: 0,6 a 5,6; p=0,025). En los demás componentes no hubo diferencias significativas.La intervención educativa incrementó en un 59,3% la proporción de estudiantes libres de algún componente del síndrome metabólico.

Left ventricular (LV) interaction with the arterial system (arterial-ventricular coupling, AVC) is a central determinant of cardiovascular performance and cardiac energetics. Stress Echocardiography (SE) constitutes a valuable clinical tool in both diagnosis and risk stratification of patients with suspected and established coronary artery disease. Cluster Analysis (CA), an unsupervised Machine Learning technique, defines an exploratory statistical method which can be used to uncover natural groups within data.To evaluate the capacity of CA to identify uncoupled groups with ischemic condition based on SE baseline information.CA was applied to SE data acquired at baseline and peak exercise (PE) conditions. Obtained clusters were evaluated in terms of coupling conditions and LV wall motility alterations.Inter cluster significant AVC differences were obtained in terms of baseline data and changes in wall motility, confirmed by CA applied to PE data.AVC impairment was evidenced in both normal and ischemic subjects by applying CA.

The COVID-19 pandemic has rapidly altered ambulatory health care delivery and may have worsened disparities in health care access. To assess the telehealth implementation experiences of ambulatory personnel in different disciplines and their perspectives on potential telehealth disparities, and to make recommendations for more equitable telehealth delivery. We used a convergent parallel mixed-methods design. Clinic managers from geriatric medicine, internal medicine, and psychiatry e-mailed a survey to clinicians and staff regarding experiences with telehealth care delivery. Quantitative survey responses were analyzed with Fisher’s Exact tests. Qualitative responses were coded thematically. Recommendations were categorized by type of implementation strategy. Quantitative and qualitative findings on telehealth disparities were merged in a joint data display. Respondents (n = 147, 57% response rate) were distributed across three specialties: 66% internal medicine, 19% psychiatry, and 14% geriatric medicine. Prior to 2020, 77% of clinicians had never delivered telehealth services. By Spring 2020, 78% reported conducting more than half of clinic visits by telehealth. Among clinicians, 52% agreed/strongly agreed that rapid telehealth implementation exacerbated access to care disparities to: older adult patients, those with limited internet access, and those needing interpretation services. Staff expressed similar difficulties with telehealth set-up especially for these patients. To improve telehealth equity, clinicians recommended to: (i) change infrastructure; (ii) train and educate stakeholders; and (iii) support clinicians. Clinicians and staff reported specific subpopulations had challenges in accessing telehealth visits. To avoid perpetuating telehealth access disparities, further co-discovery of equitable implementation strategies with patients and clinics are urgently needed.

Aim: To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS). Methods: Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio Results: The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01–0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988–0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively. Conclusions: COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19., SCOPUS: ar.j, info:eu-repo/semantics/published

Combinations of therapies are currently recommended for patients with severe pulmonary arterial hypertension (PAH), and excellent results have been reported with triple upfront combination of these drugs. We evaluated the effects of this approach on right ventricular (RV) function and outcome in patients with severe PAH.Twenty-one patients (age, 44 ± 15 years) with newly diagnosed high-risk idiopathic PAH that was nonreversible by the inhalation of nitric oxide were treated upfront with a combination of ambrisentan, tadalafil, and subcutaneous treprostinil between 2014 and 2018. Clinical evaluation, World Health Organization functional class, 6-min walk distance, biomarkers, echocardiography, and right-sided heart catheterization data were recorded at baseline and during follow-up.At a median follow-up of 2 years, all patients were still alive. The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management score decreased from 10 ± 1 to 5 ± 1, right-sided atrial pressure decreased from 13 ± 3 to 5 ± 2 mm Hg, mean pulmonary artery pressure decreased from 60 ± 9 to 42 ± 5 mm Hg, pulmonary vascular resistance (PVR) decreased from 16.4 ± 4.4 to 5.5 ± 1.3 Wood units, N-terminal pro-brain natriuretic peptide decreased from 3,379 ± 1,921 to 498 ± 223 pg/mL, and World Health Organization functional class decreased from 3.4 ± 0.5 to 2.0 ± 0.4 (all P .001). Cardiac index increased from 1.8 ± 0.3 to 3.5 ± 0.8 L/min/mTriple upfront combination therapy with ambrisentan, tadalafil, and subcutaneous treprostinil in severe nonreversible PAH is associated with considerable clinical and hemodynamic improvement and right-sided heart reverse remodeling.

Objectives Abdominal obesity (AO) has become a public health issue due to its impact on health, society and the economy. The relationship between socioeconomic disparities and the prevalence of AO has yet to be studied in Peru. Thus, our aim was to analyze the socioeconomic inequalities in AO distribution defined using the International Diabetes Federation (IDF) cut-off points in Peruvian adults in 2018–2019. Methods This was a cross-sectional study using data from the 2018–2019 Demographic and Family Health Survey (ENDES) of Peru. We analyzed a representative sample of 62,138 adults over 18 years of age of both sexes from urban and rural areas. Subjects were grouped into quintiles of the wealth to calculate a concentration curve and the Erreygers Concentration Index (ECI) in order to measure the inequality of AO distribution. Finally, we performed a decomposition analysis to evaluate the major determinants of inequalities. Results The prevalence of AO among Peruvian adults was 73.8%, being higher among women than men (85.1% and 61.1% respectively, p < 0.001). Socioeconomic inequality in AO was more prominent among men (ECI = 0.342, standard error (SE) = 0.0065 vs. ECI = 0.082, SE = 0.0043). The factors that contributed most to inequality in the prevalence of AO for both sexes were having the highest wealth index (men 37.2%, women 45.6%, p < 0.001), a higher education (men 34.4%, women 41.4%, p < 0.001) and living in an urban setting (men 22.0%, women 57.5%, p < 0.001). Conclusions In Peru the wealthy concentrate a greater percentage of AO. The inequality gap is greater among men, although AO is more prevalent among women. The variables that most contributed to inequality were the wealth index, educational level and area of residence. There is a need for effective individual and community interventions to reduce these inequalities.

INTRODUCTION: Arterial-ventricular coupling (AVC) has been recognized as a key determinant of global cardiovascular performance. Diastolic dysfunction (DD) occurs when inadequate filling of the ventricles is related to an abnormal elevation of intracardiac filling pressures. In some cases, DD is evidenced during cardiac stress, provoked by exercise. OBJECTIVE: To evaluate AVC in individuals with stress evidenced DD, in relation to controls. MATERIALS AND METHODS: Stress echocardiography was applied to assess cardiac function during exercise. Arterial-ventricular coupling was evaluated, based on the assessment of left ventricular and arterial elastances. RESULTS: AVC showed a significant difference at peak exercise compared to controls, basically due to a loss of cardiac contractility. CONCLUSION: The manifestation of AVC coupling imbalance could act as a complementary parameter to support the diagnosis of DD.

Point-of-care ultrasound (POCUS) enables physicians to make critical diagnosis and treatment decisions at the bedside. However, access to and expertise with this technology remain limited in Peru. Establishing longitudinal POCUS educational curriculums in remote, low-resource settings can be challenging due to geographical distances, encumbering the ability to provide ongoing hands-on support. Previously described educational interventions have focused on training individual users on clinical applications of POCUS, rather than training physicians how to teach POCUS, thereby limiting scalability and sustainable impact. We therefore describe our experiences establishing the first ultrasound fellowship curriculum in Peru, which incorporates tele-ultrasonography to circumvent traditional geographical barriers.

Background: Psoriasis (Ps) is a chronic systemic autoimmune disease associated with pruritus in 64–98% of patients. However, few modestly sized studies assess factors associated with psoriatic pruritus. Objective: To investigate factors associated with Ps pruritus intensity. Methods: Psoriasis patients 18years or older seen in one of 155 centres in Italy between September 2005 and 2009 were identified from the Italian PsoCare registry. Patients without cutaneous psoriasis and those with missed information on pruritus were excluded. Results: We identified 10802 patients, with a mean age 48.8±14.3years. Mild itch was present in 33.2% of patients, moderate in 34.4%, severe in 18.7% and very severe in 13.7%. Higher itch intensity was associated with female gender, lower educational attainment compared to university degree, pustular psoriasis, psoriasis on the head, face, palmoplantar areas, folds and genitalia, more severe disease, disease duration

Pathfinders is a 10-session program developed in a community setting to creatively address the diverse needs of bereaved children and families, prevent complications of grief and trauma, and promote healthy adaptation. It is an accessible, grief-focused and trauma-informed family systems model that is theory-driven, research-informed, and grounded in practice-based evidence. Pathfinders incorporates principles central to narrative approaches, with a focus on restorative processes for helping children and families stay on track developmentally. This article outlines the structure, process, and content of Pathfinders, including examples of creative interventions used within the program.

A systematic review of the literature was conducted to investigate suicidal self-directed violence and homelessness among US military veterans, and identify existing suicide prevention strategies. In November 2015, MEDLINE, EMBASE, PsycInfo, CINAHL, Web of Science, Cochrane Library, Google, and Google Scholar were searched. Articles published since 1990 investigating self-directed violence among homeless veterans were identified. Data were extracted and synthesized qualitatively. Nineteen observational studies were included. Suicide ideation rates were 1.3% (current), 7.0% (past week), 12.1%-18% (past 30 days), and 74% (lifetime). Suicide attempt rates were 0%-6% (past 30 days), 30.7%-31.5% (past 5 years), and 15%-46.6% (lifetime). Death by suicide rate was 81.0 per 100,000. No interventional studies to prevent self-directed violence among homeless veterans were identified. Homeless veterans are at risk for self-directed violence, suggesting the need for research to examine preventive strategies. A comprehensive public health approach to suicide prevention needs to focus on vulnerable populations, including homeless veterans.

The Home-Based Mental Health Evaluation (HOME) program, which engages veterans in care following psychiatric hospitalization, was evaluated. Thirty-four veterans who participated in the HOME program were compared to 34 veterans from a matched archival control group on treatment engagement and implementation outcomes. Veterans who participated in the HOME program were significantly more likely to engage in care, engaged in care more quickly, and attended significantly more individual mental health appointments. Veterans reported high levels of satisfaction. Results suggest that the HOME program is effective at engaging veterans in care during the high-risk period of time following psychiatric hospitalization.

ObjectivesVagus nerve stimulation (VNS), most likely via enteric neurons, prevents postoperative ileus (POI) by reducing activation of alpha7 nicotinic receptor (α7nAChR) positive muscularis macrophages (mMφ) and dampening surgery-induced intestinal inflammation. Here, we evaluated if 5-HT4 receptor (5-HT4R) agonist prucalopride can mimic this effect in mice and human.DesignUsing Ca2+ imaging, the effect of electrical field stimulation (EFS) and prucalopride was evaluated in situ on mMφ activation evoked by ATP in jejunal muscularis tissue. Next, preoperative and postoperative administration of prucalopride (1–5 mg/kg) was compared with that of preoperative VNS in a model of POI in wild-type and α7nAChR knockout mice. Finally, in a pilot study, patients undergoing a Whipple procedure were preoperatively treated with prucalopride (n=10), abdominal VNS (n=10) or sham/placebo (n=10) to evaluate the effect on intestinal inflammation and clinical recovery of POI.ResultsEFS reduced the ATP-induced Ca2+ response of mMφ, an effect that was dampened by neurotoxins tetrodotoxin and ω-conotoxin and mimicked by prucalopride. In vivo, prucalopride administered before, but not after abdominal surgery reduced intestinal inflammation and prevented POI in wild-type, but not in α7nAChR knockout mice. In humans, preoperative administration of prucalopride, but not of VNS, decreased Il6 and Il8 expression in the muscularis externa and improved clinical recovery.ConclusionEnteric neurons dampen mMφ activation, an effect mimicked by prucalopride. Preoperative, but not postoperative treatment with prucalopride prevents intestinal inflammation and shortens POI in both mice and human, indicating that preoperative administration of 5-HT4R agonists should be further evaluated as a treatment of POI.Trial registration numberNCT02425774.

Introduction: Cirrhosis is associated with changes in the cardiovascular system, where the circulatory dysfunction is compensated by the development of a hyperdynamic circulation. Endothelial function can be understood as the endothelium capability to release Nitric Oxide (NO) where an impairment in the normal development of this process constitutes a main step in the genesis and progression of atherosclerosis, a major cause of cardiovascular events. In recent years, non-invasive measurements have gained attention, due to the potential complications associated to invasive procedures. Objective: To evaluate endothelial function (EF) in patients with cirrhosis, in different stages of the disease, complemented with hemodynamic measurements. Methods: Individuals were divided in three age groups, according to the severity of their disease. EF was assessed by using the flow mediated dilation technique (FMD), jointly with noninvasive determination of cardiac output (CO), total peripheral resistance (TPR) and arterial compliance (AC). Results: TPR showed a decrease in advanced severity while AC had an increase. Particularly, EF was found to be higher in CHC group, decreasing in CHB and more pronounceably in CHA. Concomitantly, an inverse behavior was observed regarding CO evolution. Conclusion: EF was noninvasively evaluated in cirrhosis, in terms of the progression of the disease. Hyperdynamic states in the more advanced condition were accompanied by a higher vascular reactivity, probably associated with higher peripheral NO release and increased AC.

Introduction: Hypertrophic cardiomyopathy (HCM) is associated with altered hemodynamics in the left ventricular outflow tract and tissue abnormalities. Exercise testing has become an integral and powerful tool for the noninvasive evaluation of HCM and, in some patients, it could define a treatment strategy. Obiective: To model the hemodynamic alterations during exercise in healthy and HCM patients, obtained by noninvasive methods. Methods: Cardiac output (CO), heart rate (HR), arterial blood pressure (ABP) and Total Peripheral Resistance (TPR) were assessed during exercise. The evaluation included a curve-fitting approach (sigmoidal model) that allowed a quantitative comparison of CO profiles. Results: When compared to controls, patients with HCM showed reduced peak exercise cardiac output and demonstrated high peripheral resistance during exercise. Analysis of modeled it CO curves revealed a higher maximum rate of recovery in healthy individuals than in HCM patients. Conclusion: The application of the sigmoidal model showed to be efficient in the characterization of CO dynamics for the different studied groups.

In order to determine the sociodemographic characteristics of human papillomavirus (HPV) in patients referred to the National Institute of Neoplastic Diseases (INEN) between 2012-2014, the detection of HPV in cervical cells was performed by polymerase chain reaction (PCR). In 465 cervical samples, 151 (32.5%) cases were HPV positive. The most common genotypes were HPV-16 (23.8%) and HPV-6 (11.9%). The presence of HPV was higher in women aged 17-29 years (OR = 2.64, 95% CI 1.14 to 6.13) and single women (OR = 2.31, 95% CI 1.37 to 3.91). The presence of genotypes of high-risk HPV was higher in single women (OR = 2.19, 95% CI 1.04 to 4.62). In conclusion, young and single women had a higher frequency of HPV-positive cases. Therefore participation by these groups should be emphasized in screening programs with combined molecular and cytological methods in order to detect the risk of developing cervical cancer in a timely manner. Con el objetivo de determinar las características sociodemográficas del virus de pacientes con papiloma humano (VPH) referidas al Instituto Nacional de Enfermedades Neoplásicas (INEN) durante los años 2012-2014, se realizó la detección del VPH en células cervicales por reacción en cadena de la polimerasa (PCR). En 465 muestras cervicales se detectaron 151 (32,5%) casos de VPH positivas. Los genotipos más frecuentes fueron VPH-16 (23,8%) y VPH-6 (11,9%). La presencia de VPH fue mayor en mujeres de 17 a 29 años (OR 2,64, IC 95%:1,14-6,13) y solteras (OR 2,31, IC 95%: 1,37-3,91), la presencia de genotipos de VPH de alto riesgo fue mayor en solteras (OR 2,19, IC 95%: 1,04-4,62). En conclusión, mujeres jóvenes y solteras presentaron mayor frecuencia de casos VPH-positivos a quienes se debe enfatizar la participación en programas de tamizaje con métodos moleculares y citológicos combinados, a fin de detectar oportunamente el riesgo de desarrollar cáncer de cuello uterino.

Background Postoperative ileus (POI) is characterized by impaired gastrointestinal motility resulting from intestinal handling-associated inflammation. The introduction of laparoscopic surgery has dramatically reduced the duration of POI. However, it remains unclear to what extent this results in a reduction of intestinal inflammation. The aim of the present study is to compare the degree of intestinal inflammation and gastrointestinal transit following laparoscopic surgery and open abdominal surgery. Methods Mice were subjected to laparoscopic surgery or laparotomy alone or, in combination with standardized intestinal manipulation of the small bowel (IM). Gastrointestinal transit and intestinal inflammation were assessed 24 h after surgery by the number of myeloperoxidase (MPO) positive cells and the level of cytokine expression. The recovery time and the degree of inflammation were also analyzed in patients subjected to colectomy under open conditions (laparotomy) or laparoscopic conditions. Key Results Mice undergoing IM by laparotomy (open IM), but not by laparoscopy (Lap IM) developed a significant delay in gastrointestinal transit compared to laparotomy or laparoscopy alone. In addition, there was significant intestinal inflammation only after open IM. Similarly, cytokine levels in peritoneal lavage fluid were lower while recovery time was faster in patients subjected to colectomy under laparoscopic conditions compared to open colectomy. Conclusions & Inferences Our data confirms that intestinal inflammation is underlying the delayed gastrointestinal transit observed after open surgery. Most importantly, we demonstrate that intestinal inflammation under laparoscopic conditions is significantly lower compared to open surgery, most likely explaining the faster recovery following laparoscopic surgery.

SummaryBackground The nationwide prevalence of latent tuberculosis infection (LTBI) in Italian patients with psoriasis has never been investigated. Objectives To estimate the nationwide prevalence of LTBI in Italian patients with psoriasis who are candidates for systemic treatment. Methods Data were obtained from the Psocare Registry on those patients (n = 4946) with age > 18 years, systemic treatment at entry specified and tuberculin skin test (TST) performed according to the Mantoux method. LTBI diagnosis was based on a positive TST result in the absence of any clinical, radiological or microbiological evidence of active tuberculosis. Results Latent tuberculosis infection was diagnosed in 8·3% of patients with psoriasis (409 of 4946). The prevalence of LTBI was lower in patients on biologics than in those on conventional systemic treatments, ranging from 4·3% (19 of 444) of patients on adalimumab to 31% (eight of 26) of those on psoralen–ultraviolet A (P

Cutaneous reactions are among the most frequent side-effects of drug intake. They encompass a wide range of clinical patterns such as macular or maculopapular rashes, urticaria, eczematous or lichenoid lesions, fixed drug eruptions, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The strongest data to establish accurate estimates of rates of cutaneous reactions to drugs come from prospective collected data in population-based studies that monitor large number of patients and capture all adverse events that occur. Despite differences in the design of epidemiologic studies, there is remarkable agreement in the results. Because most drug-induced eruptions appear within the first week after the drug therapy is started, attributing an eruption to a specific drug is often straightforward but it becomes particularly difficult when the patient is taking multiple drugs. In this case epidemiologic studies can be extremely helpful in assessing the likelihood that a certain drug is responsive for that eruption. The most frequent (rashes, urticaria) and the most severe (Stevens-Johnson syndrome, toxic epidermal necrolysis) cutaneous drug reactions are considered here.

Introduction: In recent years, peripheral arterial tonometry (PAT, a non-invasive and reproducible technique) has gained considerable interest. In this sense, arterial capacity to react to vasoactive stimulus (induced by reactive hyperemia) is known as vascular reactivity (VR). Objective: Post ischemic beat to beat VR characterization was performed based on PAT measurements. Methods: Systolic Blood Pressure (SBP) and Augmentation index (AIx) variations were modeled, as a response to flow stimulus. Results: Obtained R2 values were around 70% for VR while, to a lesser degree, AIx fit was about 50% Conclusion: Beat to Beat VR was described in terms of SBP and AIx behavior. Further studies are needed to determine the clinical usefulness of the proposed indicators.

Toll-like receptors (TLRs) are crucial players in the innate immune response to microbial invaders. The lipophilic yeast Malassezia furfur has been implicated in the triggering of scalp lesions in psoriasis. The aim of the present study was to assess the role of TLRs in the defence against M. furfur infection. The expression of the myeloid differentiation factor 88 (MyD88) gene, which is involved in the signalling pathway of many TLRs, was also analysed. In addition, a possible correlation of antimicrobial peptides of the beta-defensin family to TLRs was tested. Human keratinocytes infected with M. furfur and a variety of M. furfur-positive psoriatic skin biopsies were analysed by RT-PCR, for TLRs, MyD88, human beta-defensin 2 (HBD-2), HBD-3 and interleukin-8 (IL-8) mRNA expression. When keratinocytes were infected with M. furfur, an up-regulation for TLR2, MyD88, HBD-2, HBD-3 and IL-8 mRNA was demonstrated, compared to the untreated cells. The same results were obtained when psoriatic skin biopsies were analysed. The M. furfur-induced increase in HBD-2 and IL-8 gene expression is inhibited by anti-TLR2 neutralising antibodies, suggesting that TLR2 is involved in the M. furfur-induced expression of these molecules. These findings suggest the importance of TLRs in skin protection against fungi and the importance of keratinocytes as a component of innate immunity.

A 62-year-old man presented with the unusual association of acrokeratosis verruciformis of Hopf and multiple keratoacanthomas. Both conditions were treated successfully with acitretin.

Preeclampsia/eclampsia syndrome, a major cause of maternal mortality and morbidity, has been recognized as a condition with a globally impaired endothelial function (EF). The possibility of identifying early subclinical endothelial damage during pregnancy could be of value in classifying the different hypertensive states of pregnancy, and have a positive impact in the understanding of this syndrome, as well as on the appropriate treatment of these patients. Reactive hyperemia-related changes in carotid-radial pulse wave velocity (PWVcr) were proposed as an alternative tool for the evaluation of EF in patients with cardiovascular risk factors. If impaired EF, which follows hypertensive disorders of pregnancy can be assessed using PWVcr changes remains still unknown. Aims: To assess and compare reactive hyperemia-related changes in PWVcr and FMD in pregnant women (healthy and with hypertensive disorders) and non pregnant women. Methods: Healthy pregnant (HP; n=13), preeclamptic (PE; n=7), non-proteinuric hypertensive (NPH; n=6) and non-pregnant (NP; n=32) women were included. Left PWVcr (strain gauge mechano-transducers), left brachial arterial diameter (B-Mode ultrasound) and blood flow velocity (Doppler ultrasound) were measured before (baseline) and after the transient ischemia of the left forearm were determined. Results: One minute after the cuff deflation, PWVcr decreased in HP (6.9 ± 1.5 to 6.0 ± 0.9 m/s, p

Carotid intima-media thickness (CIMT) is a well-established subclinical marker of atherosclerosis. Non-invasive vascular evaluation has emerged as a useful tool to aid in individual cardiovascular (CV) risk stratification and diagnose. The use of CIMT in CV risk stratification requires knowing the expected reference values for the population studied. Our aim were: a) to evaluate the relationship between aging and CIMT, b) to analyze gender and side (right vs left) related-differences in CIMT and c) to determine the CIMT reference values for an Uruguayan population taking into account aging-related CIMT changes. Methods: 367 asymptomatic subjects without known CV disease or risk factors were included in the study. Subjects were divided into six age groups. High-resolution B-mode ultrasound images of both (right and left) common carotid arteries were obtained based on the techniques and recommendations described in international consensus. Results: No significant age-related differences in CIMT between men and women were observed. The mean left CIMT was thicker compared with right CIMT in groups 4, 5 and 6. However, there were no significant differences in those groups. The nomogram model was constructed from data base, in which the 95% confidence interval was considered. Diagnosis thresholds were determined as well. Conclusion: We define reference values of CIMT for our population using gold standard techniques which contributes to standard techniques which contributes to an improved insight into clinical practice and can be used routinely for evaluation.

Flow-mediated dilatation (FMD) is the most accepted technique for the evaluation of endothelial function. However, it has been show a great inter-subject variability limiting its clinical use. Carotid-radial pulse wave velocity (PWVcr) was proposed as an alternative tool for the evaluation of endothelial function. At the present, there is no doubt that PWVcr reduces its values in response to reactive hyperemia test (RHT) in healthy subjects. Aims: a) to determine simultaneously the temporal profile of FMD, PWVcr and shear rate in response to RHT and b) to describe and analyze how subjects “FMD responders” or “non-responders” behave regards to PWVcr changes. Methods: 34 healthy young subjects were included. The PWVcr (strain gauge mechanotransducers), brachial diameter (B-Mode ultrasound and blood flow velocity (Doppler ultrasound) were measured before (baseline) the cuff was inflated and after its deflation (5 minutes). 10th percentiles FMD and PWVcr changes in the population were used for the definition of the subjects (“responders and non-responders”). Results: Changes in PWVcr, brachial arterial diameter and shear rate were evidenced after the cuff release (p

Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness. However, the absence of standardized methodologies of study and lack of normal and references values have limited wider implementation of PWV in clinical practice. In this work normal PWV levels were determined in a Uruguayan population and the obtained values were analyzed taking into account data from other populations. The differences between the 'real' PWV levels and the PWV calculated using different wave detection algorithms and path lengths were assessed, and compared the taking into account the changes in PWV with aging.The Uruguayan population showed a rate of PWV increase comparable to that reported previously in non-hypertensive European subjects, although overall, PWV values were approximately 2 m/s higher in the Uruguayan population. The different approaches used to calculate the PWV showed differences in their availability to follow aging-variations in 'adjusted' (or 'real') PWV.

In this work we present an initiative to develop a national (Uruguayan) program to evaluate vascular age and to detect pre-clinical atherosclerosis using: gold-standard technologies; complimentary and integrative approaches to asses arterial functional and structural indexes; data bases systems to process, analyze and determine normal and reference values and to identify the most sensitive markers of vascular changes for different ages. We evaluated, in a Uruguayan population complementary structural and functional vascular parameters that associate aging-related changes and are considered markers of sub-clinical atherosclerosis. Traditional CV risk factors were assessed. The subjects (n=281) were submitted to non-invasive vascular studies to evaluate: 1) Common carotid artery (CCA) intima-media thickness and diameter waveforms, 2) CCA stiffness, 3) aortic stiffness (pulse wave velocity) and 4) peripheral and central pressure pulse wave derived parameters. Age groups: 21-30, 31-40, 41-50, 51-60, and 61-70 years-old. Age-related profiles were obtained for the different vascular parameters, and their utility to assess vascular changes in young, middle-aged and old subjects was evaluated. The work has the strength of being the first that uses, in Latin-America an integrative approach to characterize vascular aging-related changes.

Gender-related difference in cardiovascular diseases is one of the most investigated and still unsolved issues. Finding an explanation to this topic might have important implications for the understanding of the differences between men and women in diseases and possibly lead to the development of gender-specific strategies for its management. Recent studies have proposed that the capacitive or reservoir function of the aorta and large elastic arteries plays a major role in determining the pulse wave morphology. The pressure waveform can be explained in terms of a reservoir pressure related to arterial compliance and an "excess" or wave-related pressure associated with traveling waves. Gender-differences in the ascending aorta pressure waveform reservoir and excess components are to be characterized. The aim of this study was to evaluate, by means of a mathematical approach, gender-related differences in the central aortic pressure waveform components. Central aortic pressure waveform was non-invasively obtained in 22 healthy subjects (Age: 20 years old; 11 female). Males and females showed differences in the level and time to maximal excess pressure component, but no gender-related differences were found in the reservoir one.

Study of humans aging has presented difficulties in separating the aging process from concomitant disease and/or in defining normality and abnormality during its development. In accordance with this, aging associates structural and functional changes evidenced in variations in vascular parameters witch suffer alterations during atherosclerosis and have been proposed as early markers of the disease. The absence of adequate tools to differentiate the expected (normal) vascular changes due to aging from those related with a vascular disease is not a minor issue. For an individual, an early diagnosis of a vascular disease should be as important as the diagnosis of a healthy vascular aging. Recent studies have proposed that the capacitive or reservoir function of the aorta and large elastic arteries plays a major role in determining the pulse wave morphology. The arterial pressure waveform can be explained in terms of a reservoir pressure, related to the arterial system compliance, and an "excess" or wave-related pressure, associated with the traveling waves. The aim of this study was to evaluate, by means of a mathematical approach, age-related changes in measured, reservoir and excess central aortic pressure in order to determine if age-related changes are concentrated in particular decades of life. Central aortic pressure waveform was non-invasively obtained in healthy subjects (age range: 20-69 years old). Age-related profiles in measured, reservoir and excess pressure were calculated.

BACKGROUND Electrical stimulation of the cervical vagus nerve (VNS) prevents postoperative ileus (POI) in mice. As this approach requires an additional cervical procedure, we explored the possibility of peroperative abdominal VNS in mice and human. METHODS The effect of cervical and abdominal VNS was studied in a murine model of POI and lipopolysaccharide (LPS)-induced sepsis. Postoperative ileus was quantified by assessment of intestinal transit of fluorescent dextran expressed as geometric center (GC). Next, the effect of cervical and abdominal VNS on heart rate was determined in eight Landrace pigs to select the optimal electrode for VNS in human. Finally, the effect of sham or abdominal VNS on LPS-induced cytokine production of whole blood was studied in patients undergoing colorectal surgery. KEY RESULTS Similar to cervical VNS, abdominal VNS significantly decreased LPS-induced serum tumor necrosis factor-α (TNFα) levels (abdominal VNS: 366±33 pg/mL vs sham: 822±105 pg/mL; P

Dermoscopy used by experts has been demonstrated to improve the diagnostic accuracy for melanoma. However, little is known about the diagnostic validity of dermoscopy when used by nonexperts.

Rabies remains endemic in Peru. In 1983, Latin America and the Caribbean promised to eliminate canine-transmitted rabies from the continent. This led to Peru introducing a multidisciplinary public health system for controlling and managing rabies across the country. The system consists of mass canine vaccination campaigns, post exposure prophylaxis and monitoring aggressor animals for signs of rabies. The Peruvian city of Trujillo, La Libertad, is an urban area where dogs are the principal reservoir for rabies. The disease burden of rabies in Trujillo, La Libertad is currently minimal, with no rabies cases in humans for over 10 years, and only three canine cases. No human deaths due to rabies have occurred for several decades. From this it can be inferred that antirabies systems such as this do have real effects in reducing cases of human rabies at a grass roots level.

Background: Some studies have shown that switching patients from one tumor necrosis factor (TNF)-alfa inhibitor to another may be beneficial when they have an inadequate response or an adverse event. Objective: We sought to assess the variables predicting the efficacy of the second TNF-alfa inhibitor in patients discontinuing the first TNF-alfa inhibitor. Methods: Data from all 5423 consecutive patients starting TNF-alfa inhibitor therapy for psoriasis between September 2005 and September 2010 who were included in the Italian Psocare registry were analyzed. Results: In 105 patients who switched to a second TNF-alfa inhibitor who had complete follow-up data, 75% improvement in the Psoriasis Area Severity Index score (PASI 75) was reached by 29% after 16 weeks and by 45.6% after 24 weeks. Patients who switched because of secondary loss of efficacy (loss of initial PASI 75 response) or adverse events/intolerance were more likely to reach PASI 75 than those who switched as a result of primary inefficacy (PASI 75 never achieved) (hazard ratio 2.7, 95% confidence interval 1.3-5.5 vs hazard ratio 2.0, 95% confidence interval 1.0-3.9 and 1, respectively). Limitations: There was a small number of patients with complete follow-up data. Conclusion: PASI 75 response in patients who switched from one antie-TNF-alfa agent to another was significantly reduced in patients who showed primary inefficacy of the first antie-TNF-alfa.

Background: Postoperative ileus is characterized by a transient impairment of the gastrointestinal motility after abdominal surgery. The intestinal inflammation, triggered by handling of the intestine, is the main factor responsible for the prolonged dysmotility of the gastrointestinal tract. Secondary lymphoid organs of the intestine were identified as essential components in the dissemination of inflammation to the entire gastrointestinal tract also called field effect. The involvement of the spleen, however, remains unclear. Aim: In this study, we investigated whether the spleen responds to manipulation of the intestine and participates in the intestinal inflammation underlying postoperative ileus. Methods: Mice underwent Laparotomy (L) or Laparotomy followed by Intestinal Manipulation (IM). Twenty-four hours later, intestinal and colonic inflammation was assessed by QPCR and measurement of the intestinal transit was performed. Analysis of homeostatic chemokines in the spleen was performed by QPCR and splenic cell populations analysed by Flow Cytometry. Blockade of the egress of cells from the spleen was performed by administration of the Sphingosine-1phosphate receptor 1 (S1P1) agonist CYM-5442 10 h after L/IM. Results: A significant decrease in splenic weight and cellularity was observed in IM mice 24 h post-surgery, a phenomenon associated with a decreased splenic expression level of the homeostatic chemokine CCL19. Splenic denervation restored the expression of CCL19 and partially prevented the reduction of splenocytes in IM mice. Treatment with CYM-5442 prevented the egress of splenocytes but did not ameliorate the intestinal inflammation underlying postoperative ileus. Conclusions: Intestinal manipulation results in two distinct phenomena: local intestinal inflammation and a decrease in splenic cellularity. The splenic response relies on an alteration of cell trafficking in the spleen and is partially regulated by the splenic nerve. The spleen however does not participate in the intestinal inflammation during POI.

OBJECTIVE: To evaluate variations in laboratory parameters and diagnoses of selected clinical conditions up to 16 weeks after starting a new systemic psoriasis treatment for Psocare Registry enrollees. DESIGN: Prospective cohort study. SETTING: Italian public referral centres for psoriasis treatment. PATIENTS: First-time recipients (n = 10,539) of continuous systemic psoriasis treatment for at least 16 weeks. MAIN OUTCOME MEASURE: Mean variations in (weeks 8 and 16) and proportions of patients reaching a clinically meaningful increase in serum levels (week 16) of total and low-density lipoprotein cholesterol, triglycerides, aspartate amino transferase, alanine amino transferase and creatinine, as well as week-16 cumulative incidences of new diagnoses of diabetes mellitus and arterial hypertension. RESULTS: Mean cholesterol and triglyceride levels significantly increased in patients treated with acitretin or cyclosporine. Mean triglyceride levels also increased in efalizumab- and etanercept-treated patients. Mean transaminase values increased in methotrexate-treated patients, and mean aspartate amino transferase levels increased in infliximab-treated patients. The average serum creatinine value increased in cyclosporine-treated patients. Acitretin and cyclosporine were associated with risk of hypercholesterolaemia (odds ratios 1.51 and 1.34) and acitretin with risk of hypertriglyceridaemia (odds ratio 1.43). Methotrexate and infliximab were associated with risk of more than doubling the upper normal aspartate amino transferase (odds ratios 2.06 and 1.87) and alanine amino transferase (odds ratios 2.38 and 1.74) values. The relative risk of developing arterial hypertension and diabetes was increased for patients receiving cyclosporine (odds ratios 3.31 and 2.88). CONCLUSION: Systemic treatments for psoriasis resulted in heterogeneous effects on the parameters analysed.

This paper reports on a qualitative study to identify Italian nurses' feelings and emotions towards the management of distressed and disturbed psychiatric patients in acute inpatient settings. Four focus groups were carried out involving 33 nurses from seven acute psychiatric services in a region of Italy. Data were analysed using content analysis. Findings highlight that fear is the prevailing feeling experienced by nurses in the management of distressed patients. This includes both fear of being physically harmed and concerns about doing harm or damage to patients. The unpredictability of aggressive behaviour from unknown patients was described as especially frightening. Known patients, namely those previously admitted to the unit, induced less fear, as their behaviour was considered more predictable. Patients with dual diagnosis were also a worry for many nurses, who considered themselves lacking in the personal relational skills needed to manage an individual in crisis. Nurses reported that they try to understand the reasons for a patient's aggressive behaviour and are empathetic to his or her suffering. When such empathy is lacking, nurses experience conflicting feelings of counter-aggressiveness. The paper concludes by emphasizing the need to increase availability of education related to patient management, in particular team working and its internal relationships.

An observational multicenter study was carried out in Italy, to evaluate the acceptability and safety of the new intradermal (ID) influenza vaccine (Intanza Sanofi Pasteur SA, Lyon, France) among subjects aged≥60 years, compared with that of other intramuscular (IM) influenza vaccines. Compliance with the use of the ID vaccine by healthcare professionals was also assessed.A previously validated and self-administered questionnaire, Vaccinees' Perception of Injection (VAPI®), consisting of 21 questions, mainly focused on four dimensions (bother, arm movements, sleep, and acceptability), was administered to1,600 individuals with spontaneous access to outpatient clinics, located in Northern, Central, and Southern Italy, to evaluate the acceptance of the vaccines. Occurrence of solicited and unsolicited side effects and of serious adverse events was assessed in a subset of subjects (n=500), using a clinical diary filled in by vaccinees following immunization. Compliance with the new ID vaccine by healthcare professionals was investigated using an ad-hoc questionnaire.A very favorable opinion concerning the acceptability of both the vaccines under survey, with the most positive answers ranging between 75.5% and 94.9%, was registered within the study population. Also the compliance by healthcare professionals (n=130) with the novel ID vaccine was favorable. No serious adverse event occurred during the 6-month follow-up period. The frequency of solicited systemic reactions was comparable between the two study groups, while solicited local reactions were significantly higher in the ID-vaccine group than in the IM-vaccine group, even if at values lower than those reported in phase 3 clinical trials (ranges=18.5-32.6% vs. 29.5-70.9%). These local events were mild and transient, thus without any clinical relevance.The novel ID influenza vaccine can be widely recommended in clinical practice, representing a useful tool to improve immunization coverage rates, and thus the control of influenza.

Dermoscopy used by experts has been demonstrated to improve the diagnostic accuracy for melanoma. However, little is known about the diagnostic validity of dermoscopy when used by nonexperts.To evaluate the diagnostic performance of nonexperts using a new 3-point checklist based on a simplified dermoscopic pattern analysis.Clinical and dermoscopic images of 231 clinically equivocal and histopathologically proven pigmented skin lesions were examined by 6 nonexperts and 1 expert in dermoscopy. For each lesion the nonexperts assessed 3 dermoscopic criteria (asymmetry, atypical network and blue-white structures) constituting the 3-point method. In addition, all examiners made an overall diagnosis by using standard pattern analysis of dermoscopy.Asymmetry, atypical network and blue-white structures were shown to be reproducible dermoscopic criteria, with a kappa value ranging from 0.52 to 0.55. When making the overall diagnosis, the expert had 89.6% sensitivity for malignant lesions (tested on 68 melanomas and 9 pigmented basal cell carcinomas), compared to 69.7% sensitivity achieved by the nonexperts. Remarkably, the sensitivity of the nonexperts using the 3-point checklist reached 96.3%. The specificity of the expert using overall diagnosis was 94.2% compared to 82.8 and 32.8% achieved by the nonexperts using overall diagnosis and 3-point checklist, respectively.The 3-point checklist is a valid and reproducible dermoscopic algorithm with high sensitivity for the diagnosis of melanoma in the hands of non-experts. Thus it may be applied as a screening procedure for the early detection of melanoma.

Kidney biopsies were undertaken for persisting proteinuria 3.3 to 7 years (mean 5.4 years) from the onset of diarrhea-associated hemolytic uremic syndrome (D + HUS) in 5 boys and 2 girls (age at presentation mean 3.2 years, range 1.0 to 9.7 years). At 1 year the mean early morning urine protein/creatinine ratio was 100 mg/mmol, and the mean glomerular filtration rate was 65 mL/min/1.73 m2. At 5 years the mean early morning urine protein/creatinine ratio was 81 mg/mmol, and the mean glomerular filtration rate was 73 mL/min/1.73 m2. The biopsy specimens were compared with those of 7 age- and sex-matched children who were investigated for isolated persistent microscopic hematuria but in whom no abnormality was detected. Global glomerulosclerosis was noted in 6 patients with D + HUS, and 2 of these had segmental sclerosing lesions. Tubular atrophy and interstitial scarring were seen in all but 1 patients. The glomeruli in the D + HUS group were significantly larger than in the control group (P < .01). These findings are typically found in kidneys with reduced nephron numbers and are compatible with changes of hyperperfusion and hyperfiltration in surviving nephrons. Long-term follow-up of patients with D + HUS and proteinuria is advisable.

INTRODUCTION: Intestinal manipulation (IM) during abdominal surgery results in intestinal inflammation leading to hypomotility or ileus. Mast cell activation is thought to play a crucial role in the pathophysiology of postoperative ileus (POI). However, this conclusion was mainly drawn using mast cell-deficient mouse models with abnormal Kit signaling. These mice also lack interstitial cells of Cajal (ICC) resulting in aberrant gastrointestinal motility even prior to surgery, compromising their use as model to study POI. To avoid these experimental weaknesses we took advantage of a newly developed knock-in mouse model, Cpa3(Cre/+) , devoid of mast cells but with intact Kit signaling. DESIGN: The role of mast cells in the development of POI and intestinal inflammation was evaluated assessing gastrointestinal transit and muscularis externa inflammation after IM in two strains of mice lacking mast cells, i.e. Kit(W-sh/W-sh) and Cpa3(Cre/+) mice, and by use of the mast cell stabilizer cromolyn. RESULTS: Kit(W-sh/W-sh) mice lack ICC networks and already revealed significantly delayed gastrointestinal transit even before surgery. IM did not further delay intestinal transit, but induced infiltration of myeloperoxidase positive cells, expression of inflammatory cytokines and recruitment of monocytes and neutrophils into the muscularis externa. On the contrary, Cpa3(Cre/+) mice have a normal network of ICC and normal gastrointestinal. Surprisingly, IM in Cpa3(Cre/+) mice caused delay in gut motility and intestinal inflammation as in wild type littermates mice (Cpa3(+/+) ). Furthermore, treatment with the mast cell inhibitor cromolyn resulted in an inhibition of mast cells without preventing POI. CONCLUSIONS: Here, we confirm that IM induced mast cell degranulation. However, our data demonstrate that mast cells are not required for the pathogenesis of POI in mice. Although there might be species differences between mouse and human, our results argue against mast cell inhibitors as a therapeutic approach to shorten POI.

After a careful review of the Author's own case list and of the literature on this subject, Milligan-Morgans' technique is assessed and compared with different surgical techniques as far as early and late complications are concerned. The Authors conclude that the Milligan-Morgan technique is to be preferred because of its simplicity, safety and flexibility, particularly if associated with sphincterectomy, with or without rhagade, in order to prevent the cicatricial scars.

Thanks to the diffusion of the clinico-mammographic screening, in the last ten years a considerable increase of breast carcinomas diagnosed in a subclinical stage has been registered. The authors report the preliminary results of their experience in nonpalpable lesions of the breast and confirm the validity of conservative surgery for their treatment. Nonpalpable breast carcinomas must be considered as an early stage of palpable T1 tumors, for which validity of conservative surgery is largely demonstrated. Moreover, results are not compromised by possible multicentricity and/or positivity of axillary lymph nodes.

Over the years the palliative treatment of neoplastic stenosis of the esophagus in patients who cannot be operated has seen a variation of endoscopic methods which aimed to reopen the alimentary canal either using simple dilatation, or the insertion of endoprostheses, or sclerosing injection or antiblastic therapy, or lastly using disobstructive laser therapy. In particular, the use of Neodymium YAG laser in endoscopic therapy for the deobstruction of neoplastic esophageal stenosis is currently widely used. More recently deobstruction of the stenosis may also be achieved using bipolar diathermocoagulation with BICAP following esophageal dilatation. Recent comparative studies of the use of BICAP and laser therapy in the treatment of neoplastic esophageal stenosis have tended to reveal the complementary characteristics of the two techniques. The present paper reports the Authors' experience in this respect which has been satisfactory with regard to both methods, in line with the findings of other studies. In the study of two groups of 8 patients treated with BICAP and laser therapy respectively, recanalisation was obtained in 100% of cases with good functional results in 75% of patients treated with BICAP and 87.5% of those receiving laser therapy. The time interval between one treatment session and the next in relation to the efficacy of the therapy was similar in both methods and ranged from a minimum of 4 weeks to a maximum of 12 weeks. Complications were scarce in both groups.