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Chronic maxillary atelectasis (CMA) is a progressive alteration in the volume of the maxillary sinuses that may result in facial asymmetry. CMA in asymptomatic patients is known as silent sinus syndrome (SSS) and is a rare entity, especially in pediatric patients. This study reports a case of SSS in a pediatric patient who received an early diagnosis through cone-beam computed tomography (CBCT). An asymptomatic 12-year-old female patient in orthodontic treatment presented with opacification of the left maxillary sinus on a panoramic radiograph. Clinically, the patient had discrete hypoglobus and enophthalmos. CBCT and nasal video-endoscopy revealed ostiomeatal obstruction with bone deformity, leading to diagnosis of SSS. Endonasal endoscopic maxillary sinusotomy was performed. Two years later, the patient remained asymptomatic, and a second CBCT exam confirmed a stable condition. This case highlights the role of optimal radiographic interpretation for early diagnosis of maxillofacial alterations in pediatric patients.

Calciphylaxis is a potencially disorder in patients with hyperphosphatemic familial tumoral calcinosis (HFTC). Patients commonly present livedo racemosa and retiform purpura, which may progress to necrosis and very painful ulcers. Treatment with sodium thiosulfate provides good results; however, intralesional and intravenous treatment can be limited by its adverse effects. Topical sodium thiosulfate has been successfully reported for cutaneous calcification associated with connective tissue diseases and calciphylaxis in patients with chronic kidney disease. We provide a case report of a patient with HFTC and calciphylaxis who was treated with topical sodium thiosulfate with a rapid and complete response with no side effects.

Cowden syndrome is a rare autosomal dominant disorder that is characterized by multiple hamartomatous neoplasms in a variety of tissues and is associated with germline mutations in the PTEN gene. Cowden syndrome does not have increased risk of gastric malignancy; however, complications of benign neoplasm can occur. The authors report a case of a patient with Cowden Syndrome and with gastric polyps that caused severe morbidity and a surgical approach was indicated. An antrectomy with troncular vagotomy was performed with a Billroth I reconstruction. In this case, this was of paramount importance so the duodenum can be revisited.

Tejera-Vaquerizo, A (Tejera-Vaquerizo, Antonio); Paradela, S (Paradela, Sabela); Toll, A (Toll, Agusti); Santos-Juanes, J (Santos-Juanes, Jorge); Jaka, A (Jaka, Ane); Lopez, A (Lopez, Alba); Canueto, J (Canueto, Javier); Bernal, A (Bernal, Alvaro); Villegas-Romero, I (Villegas-Romero, Isabel); Fernandez-Pulido, C (Fernandez-Pulido, Carla); Perandones, H (Perandones, Hector); Moreno-Ramirez, D (Moreno-Ramirez, David); Dominguez-Mahamud, C (Dominguez-Mahamud, Carolina); Salido-Vallejo, R (Salido-Vallejo, Rafael); Sanmartin, O (Sanmartin, Onofre); Almazan-Fernandez, FM (Almazan-Fernandez, Francisco M.); Rodriguez-Jimenez, P (Rodriguez-Jimenez, Pedro); Banuls, J (Banuls, Jose); Podlipnik, S (Podlipnik, Sebastian); Sandoval-Clavijo, A (Sandoval-Clavijo, Alejandra); Boada, A (Boada, Aram); Garcia-Bracamonte, B (Garcia-Bracamonte, Beatriz); Palencia, S (Palencia, Sara); Revilla-Nevreda, D (Revilla-Nevreda, David); Reola-Ramirez, E (Reola-Ramirez, Enara); Gomez-Mateo, MD (del Carmen Gomez-Mateo, Maria); Linares-Barrios, M (Linares-Barrios, Mario); Jimenez-Gallo, D (Jimenez-Gallo, David); Gonzalez-Cruz, C (Gonzalez-Cruz, Carlos); Samaniego, E (Samaniego, Elia); Navedo-De Las Heras, M (Navedo-De Las Heras, Maria); Taberner, R (Taberner, Rosa); Rodenas-Herranz, T (Rodenas-Herranz, Teresa); Garcia-Donoso, C (Garcia-Donoso, Carmen); Puig, S (Puig, Susana); Nagore, E (Nagore, Eduardo)

The most frequently performed bariatric surgery is the laparoscopic Roux-en-Y gastric bypass (LRYGB). An uncommon complication of LRYGB is gastro-gastric fistula (GGF). Possible causes of GGF include incomplete transection of the stomach during the initial surgery, staple-line leaks in the post-operative period and marginal ulcers. The optimal management of GGF is still under debate, with medical, endoscopic and surgical treatment modalities available. The authors present two cases of a GGF successfully managed with a laparoscopic surgical approach, after failed medical and endoscopic treatment.

Background and objectives: The efficacy and safety of ustekinumab have been proved in clinical trials. In daily clinical practice, knowing the factors that determine survival differences of biological drugs allows psoriasis treatment to be optimized as a function of patient characteristics. The main objectives of this work are to understand ustekinumab drug survival in patients diagnosed with plaque psoriasis in the Hospital Universitario Central de Asturias (HUCA Dermatology Department, and to identify the predictors of drug discontinuation. Materials and Methods: A retrospective hospital-based study, including data from 148 patients who were receiving ustekinumab (Stelara&reg, ) between 1 February 2009 and 30 November 2019, were collected. Survival curves were approximated through the Kaplan&ndash, Meier estimator and compared using the log-rank test. Proportional hazard Cox regression models were used for multivariate analyses while both unadjusted and adjusted hazard ratios (HR) were used for summarizing the studied differences. Results: The average duration of the treatment before discontinuation was 47.57 months (SD 32.63 months, median 41 months). The retention rates were 82% (2 years), 66% (5 years), and 58% (8 years). Median survival was 80 months (95% confidence interval. CI 36.9 to 123.01 months). The survival study revealed statistically significant differences between patients with arthritis (log-rank test, p &lt, 0.001) and those who had previously received biological treatment (log-rank test, p = 0.026). The five-year prevalence in patients still under treatment was 80% (those without arthritis) and 54% (arthritis patients). In the multivariate analysis, only the patients with arthritis had a lower rate of drug survival. No statistically significant differences were observed for any of the other comorbidities studied. The first and second most frequent causes of discontinuation were secondary failure and arthritis inefficacy, respectively. Conclusion: Ustekinumab is a biological drug conferring high survival in plaque psoriasis patients. Ustekinumab survival is lower in patients with arthritis.

Background Neglected tropical diseases (NTDs) comprise 20 communicable diseases that are prevalent in rural poor and remote communities with less access to the health system. For effective and efficient control, the WHO recommends that affected countries implement integrated control interventions that take into account the different co-endemic NTDs in the same community. However, implementing these integrated interventions involving several diseases with different etiologies, requiring different control approaches and driven by different vertical programs, remains a challenge. We report here the results and lessons learned from a pilot test of this integrated approach based on integrated screening of skin diseases in three co-endemic health districts of Côte d’Ivoire, a West African country endemic for Buruli ulcer, leprosy and yaw. Method This cross-sectional study took place from April 2016 to March 2017 in 3 districts of Côte d’Ivoire co-endemic for BU, leprosy and yaws. The study was carried out in 6 stages: identification of potentially co-endemic communities; stakeholder training; social mobilization; mobile medical consultations; case detection and management; and a review meeting. Results We included in the study all patients with skin signs and symptoms at the screening stage who voluntarily accepted screening. In total, 2310 persons screened had skin lesions at the screening stage. Among them, 07 cases were diagnosed with Buruli ulcer. There were 30 leprosy cases and 15 yaws detected. Other types of ulcerations and skin conditions have been identified and represent the majority of cases detected. We learned from this pilot experience that integration can be successfully implemented in co-endemic communities in Côte d’Ivoire. Health workers are motivated and available to implement integrated interventions instead of interventions focused on a single disease. However, it is essential to provide capacity building, a minimum of drugs and consumables for the care of the patients identified, as well as follow-up of identified patients, including those with other skin conditions. Conclusions The results of this study show that the integration of activities can be successfully implemented in co-endemic communities under the condition of staff capacity building and minimal care of identified patients.

TSC; Resource use; TOSCA TSC; Uso de recursos; TOSCA TSC; Ús de recursos; TOSCA Tuberous Sclerosis Complex (TSC) is a rare autosomal-dominant disorder caused by mutations in the TSC1 or TSC2 genes. Patients with TSC may suffer from a wide range of clinical manifestations; however, the burden of TSC and its impact on healthcare resources needed for its management remain unknown. Besides, the use of resources might vary across countries depending on the country-specific clinical practice. The aim of this paper is to describe the use of TSC-related resources and treatment paterns within the TOSCA registry. A total of 2,214 patients with TSC from 31 countries were enrolled and had a follow-up of up to 5 years. A search was conducted to identify the variables containing both medical and non-medical resource use information within TOSCA. This search was performed both at the level of the core project as well as at the level of the research projects on epilepsy, subependymal giant cell astrocytoma (SEGA), lymphangioleiomyomatosis (LAM), and renal angiomyolipoma (rAML) taking into account the timepoints of the study, age groups, and countries. Data from the quality of life (QoL) research project were analyzed by type of visit and age at enrollment. Treatments varied greatly depending on the clinical manifestation, timepoint in the study, and age groups. GAB Aergics were the most prescribed drugs for epilepsy, and mTOR inhibitors are dramatically replacing surgery in patients with SEGA, despite corrent recommendations proposing both treatment options.mTOR inhibitors are also becoming common treatments in rAML and LAMpatients. Forty-two out of the 143 patients (29.4%) who participated in the QoL research project reported inpatient stays over the last year. Data from non-medical resource use showed the critical impact of TSC on job status and capacity. Disability allowances were more common in children than adults (51.1% vs 38.2%). Psychological counseling, social services and social worker services were needed by

Objective: The main aim of this study is to identify, appraise and synthesize evidence on the level of physical activity and sedentary behavior in older adults. Method: This review was restricted to studies published between January 2006 and January 2019 and included studies that reported physical activity and sedentary behavior in older adults (≥65 years old) without chronical health conditions. Results: Twenty studies met the inclusion criteria. Two studies reported data for older adults residing at assisted care facilities, showing results of moderate to vigorous physical activity much lower than those reported in studies with older adults living in the community (2 min/per day and 37.2 min/per day, respectively). Conclusion: Sedentary behavior is high in the elderly, with men presenting higher values than women. moderate to vigorous physical activity has very low values, and with the advancing age there is a decrease in the same.

Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immunoglobulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs.

Glioblastoma (GBM) ranks among the most challenging cancers to treat and there is an urgent need for clinically relevant prognostic and diagnostic biomarkers. Here, we set out to investigate the expression of eight proteins (bcl-2, cyclin D1, p16, p21, p27, p53, Sox11 and WT1) in GBM with the specific aim to establish immunohistochemistry cut-off points with clinical relevance.Immunohistochemistry (IHC) was used to examine protein expression in 55 surgical GBM specimens using H-scores, and IHC cut-off points were established using the Cutoff Finder web platform. Protein co-expression and its correlation with histopathological features were assessed, and cases were classified according to IDH1 mutation status. Survival curves were determined using Kaplan-Meier analyses.Clinical and molecular parameters found to be correlated with overall survival (OS) were tumor size (r = -0.278; p = 0.048), p53 (r = -0.452; p = 0.001), p16 (r = 0.351; p = 0.012) and Sox11 (r = 0.324; p = 0.020). In addition, we found that tumor size correlated with cyclin D1 (r = -0.282; p = 0.037), p53 (r = 0.269; p = 0.041), Sox11 (r = -0.309; p = 0.022) and WT1 (r = -0.372; p = 0.003). Variables found to be significantly associated with IDH1 mutation status were OS (p 0.01), age (p 0.01), cyclin D1 (p = 0.046), p16 (p = 0.019) and Sox11 (p = 0.012). Variables found to be significantly associated with a poor survival were tumor size5 cm (p 0.001), bcl-2 score 40 (p = 0.034), cyclin D1 score ≤ 70 (p = 0.004), p16 score ≤ 130 (p = 0.005), p53 score 20 (p = 0.003), Sox11 score ≤ 40 (p 0.001) and WT1 score ≤ 270 (p = 0.02).Correlations between protein biomarkers and main clinical GBM variables were identified. The establishment of distinct biomarker cut-off points may enable clinicians and pathologists to better weigh their prognostic value.

Background Tumor budding is a readily detectable histopathologic feature that has been recognized as an adverse prognostic factor in several human cancers. Objective We sought to assess the correlation of tumor budding with the clinicopathologic features and the prognostic value of tumor budding in cutaneous squamous cell carcinoma (cSCC). Methods Forty-nine primary nonmetastatic and 49 primary metastatic cSCCs to regional lymph nodes were retrospectively studied. Statistical analyses were carried out to assess the relationship between tumor budding, clinicopathologic parameters, and patient survival. Results Tumor budding was observed in 45 cases of 98 (46%). High-intensity budding (≥5 tumor buds) was observed in 20 tumors. Presence of tumor buds was a significant risk factor for nodal metastasis with crude and adjusted hazard ratios (HRs) of 8.92 (95% CI, 4.39-18.1) and 6.93 (95% CI, 3.30-14.5), respectively, and for reduced overall survival time (crude and adjusted HRs of 2.03 [95% CI, 1.26-3.28] and 1.72 [95% CI, 1.05-2.83], respectively). Limitations This was a retrospective study limited to cSCCs of the head and neck. Examined tumors were >2 mm thick, and all were from a primary excision. Conclusion These results indicate an increased frequency of nodal metastasis and risk of death in patients with tumor buds.

BackgroundNeglected Tropical Diseases (NTDs) comprise 20 communicable diseases that are prevalent in rural poor and remote communities with less access to the health system. For an effective and efficient control, the WHO recommends to affected countries the implementation of integrated control interventions that take into account the different co-endemic NTDs in the same community. However, implementing these integrated interventions involving several diseases with different etiologies, requiring different control approaches and driven by different vertical programs remains a challenge. We report here the results and lessons learned from a pilot test of this integrated approach based on integrated screening of skin diseases in three co-endemic health districts of Côte d'Ivoire, a West African country endemic for Buruli ulcer, leprosy and yaw three skin NTDs. MethodThis cross-sectional study took place from April 2016 to March 2017 in 3 Districts of Côte d’Ivoire co-endemic for BU, leprosy and yaws. It was carried out in 6 stages: identification of potentially co-endemic communities; stakeholder training; social mobilization; mobile medical consultations; case detection and management; and a review meeting.ResultsIn total, 2310 persons were screened with skin diseases. Among them, 07 cases were diagnosed as Buruli ulcer. There were 30 leprosy cases and 15 yaws detected. Other types of ulcerations and skin conditions have been identified and represent the majority of cases detected. We learned from this pilot experience that integration can be successfully implemented in co-endemic communities in Côte d’Ivoire. Health workers are motivated and available to implement integrated interventions instead of interventions focused on a single disease. However, it is essential to provide capacity building, a minimum of drugs and consumables for the care of the patients detected, as well as follow up of detected patients including those with other skin conditions.ConclusionsThe results of this study show that the integration of activities can be successfully implemented in co-endemic communities under the condition of a staff capacity building and a minimal care of the detected patients.

SEGA; TOSCA; Tuberous sclerosis complex SEGA; TOSCA; Complex d’esclerosi tuberosa SEGA; TOSCA; Complejo de esclerosis tuberosa The onset and growth of subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis complex (TSC) typically occurs in childhood. There is minimal information on SEGA evolution in adults with TSC. Of 2,211 patients enrolled in TOSCA, 220 of the 803 adults (27.4%) ever had a SEGA. Of 186 patients with SEGA still ongoing in adulthood, 153 (82.3%) remained asymptomatic, and 33 (17.7%) were reported to ever have developed symptoms related to SEGA growth. SEGA growth since the previous scan was reported in 39 of the 186 adults (21%) with ongoing SEGA. All but one patient with growing SEGA had mutations in TSC2. Fourteen adults (2.4%) were newly diagnosed with SEGA during follow-up, and majority had mutations in TSC2. Our findings suggest that surveillance for new or growing SEGA is warranted also in adulthood, particularly in patients with mutations in TSC2. The study was funded by Novartis Pharma AG.

SEGA; TOSCA; Tuberous sclerosis complex SEGA; TOSCA; Complejo de esclerosis tuberosa SEGA; TOSCA; Complex d'esclerosi tuberosa Background: This study evaluated the characteristics of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC) entered into the TuberOus SClerosis registry to increase disease Awareness (TOSCA). Methods: The study was conducted at 170 sites across 31 countries. Data from patients of any age with a documented clinical visit for TSC in the 12 months preceding enrollment or those newly diagnosed with TSC were entered. Results: SEGA were reported in 554 of 2,216 patients (25%). Median age at diagnosis of SEGA was 8 years (range, 18 years. SEGA were symptomatic in 42.1% of patients. Symptoms included increased seizure frequency (15.8%), behavioural disturbance (11.9%), and regression/loss of cognitive skills (9.9%), in addition to those typically associated with increased intracranial pressure. SEGA were significantly more frequent in patients with TSC2 compared to TSC1 variants (33.7 vs. 13.2 %, p < 0.0001). Main treatment modalities included surgery (59.6%) and mammalian target of rapamycin (mTOR) inhibitors (49%). Conclusions: Although SEGA diagnosis and growth typically occurs during childhood, SEGA can occur and grow in both infants and adults. The study was funded by Novartis Pharma AG. Novartis has contributed to the study design, data analysis, and the decision to publish. Novartis authors reviewed the draft for submission.

[Introduction]: Goblet cell carcinoma (GCC) is an appendicular neoplasia representing less than 5% of all appendicular tumors, found in 0.3–0.9% of the appendectomies, 35–58% of all appendicular neoplasms, and less than 14% of malign appendix tumors. The most frequent clinical presentation is abdominal pain associated with a picture of acute appendicitis., [Materials and methods]: We present 3 clinical cases of appendix GCC, 2 subjected to cytoreductory surgery plus intraperitoneal hyperthermic chemotherapy and a third, who is currently receiving neoadjuvant treatment with a good response to chemotherapy and who will be offered the same treatment as the first two patients. Given the unpredictable behavior of these tumors, the use of molecular markers could help us to predict their behavior and prognosis. In this context, the TP73 gene would make an interesting putative marker. ∆Np73 has been described as overexpressed in a great variety of tumor types including colon cancer and this up-regulation is associated with a poor prognosis. To evidence its role in this malignancy, we evaluate here the status of ∆Np73 in the primary tumor and normal counterpart tissues, in the metastatic implants and in healthy areas of the peritoneum from the appendicular GCC patients. In addition, we checked the expression levels of this p73 variant in the tumor and normal tissue of 26 patients with colon cancer., [Results]: Remarkably, 2 patients showed significant ∆Np73 down-regulation in both the primary tumor and the implants. Case 1 presented a fourfold decrease of levels in the primary tumor and 20-fold decrease in the implants. Case 2 showed a seven- and fourfold down-regulation in the primary tumor and implants, respectively. However, Case 3 showed an up-regulation of 53- and threefold in the primary tumor and implants, respectively., [Conclusion]: Goblet cell carcinoma of the appendix is very rate. It tends to seed throughout the peritoneum, making aggressive surgical cytoreduction and chemotherapy viable treatment options. Investigation into the molecular basis of these tumors may improve the diagnosis, prognosis and therapeutic decisions regarding these patients. ∆Np73 seems a good candidate for further analysis in longer series., We acknowledge ISCIII, FIS, FEDER and Cátedra UAM-ROCHE de Medicina de Innovación for funding our current research through the PI18/00473 and CIBERONIC. Gemma Domínguez and Nuria Rodriguez have received research grants from Roche Farma SA.

Colon interposition in oesophageal replacement after oesophagectomy for benign strictures is associated with significant perioperative complications that carry high morbidity and mortality. Long-term sequelae such as further strictures and colonic redundancy are frequent. Adenocarcinoma in the colonic graft is rare. A 70-year-old female presented to our clinic with symptoms of dysphagia. When she was 51 years, she underwent left colonic oesophageal interposition for an oesophageal stricture caused by caustic ingestion. Studies revealed colonic adenocarcinoma in interposed colonic graft, with latero-cervical lymph nodes. She was proposed to neoadjuvant chemotherapy. Although long-term risk analysis is lacking, it’s not unreasonable to propose endoscopic screening according to general colonic cancer guidelines in patients with colonic interposition in oesophageal replacement after oesophagectomy.

Background Sentinel lymph node biopsy and wide local excision of the primary melanoma (SLNB) is now a standard staging procedure for patients with melanomas 1 mm or more in thickness, but its therapeutic benefit is not clear. Objective To determine whether there is an association between performance of SLNB and patient prognosis. Methods Studies assessing the association between performance of SLNB and patient prognosis were pooled from MEDLINE, EMBASE, PubMed, Cochrane Database of Systematic Reviews and Google Scholar. From each study, first author's last name, publication year, origin country, type of study design, characteristics of participants and the Hazard risk (HR) for melanoma specific survival (MSS) with the corresponding 95% confidence interval (95% CI) were collected. Methodological assessment of the studies was evaluated using the Newcastle-Ottawa scale (NOS) and the ‘Risk of bias’ tool detailed in the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses for the global HR were performed. In addition, in order to explore the sources of heterogeneity among the studies, sensitivity analyses are also provided. Results A total of six studies with 8764 patients who had undergone SLNB and 11054 patients who had undergone wide location excision alone (WLEA) were identified for the analysis. The indicators suggest that the heterogeneity is low: τ2 = 0; H = 1 [1; 1.74]; I2 = 0% [0%; 66.5%]. Evidence for publication bias was not found (Egger's test P = 0.4654). The pooled MSS HR from fixed effects analysis was determined to be 0.88 (95% CI = 0.80–0.96). Conclusions Although no significant survival difference was observed in four of the six series, the pooling summary data from all the studies that deal with this issue suggested that SLNB is associated with a significantly better outcome compared with WLEA for localized melanoma.

Celiac disease (CD) is an immune-mediated, gluten-induced enteropathy that affects predisposed individuals of all ages. Many patients with CD do not report gastrointestinal symptoms making it difficult to reach an early diagnosis. On the other hand, CD is related to a wide spectrum of extra-intestinal manifestations, with dermatitis herpetiformis (DH) being the best characterized. These associated conditions may be the clue to reaching the diagnosis of CD. Over the last few years, there have been multiple reports of the association between CD and several cutaneous manifestations that may improve with a gluten-free diet (GFD). The presence of some of these skin diseases, even in the absence of gastrointestinal symptoms, should give rise to an appropriate screening method for CD. The aim of this paper is to describe the different cutaneous manifestations that have been associated with CD and the possible mechanisms involved.

Celiac disease (CD) is an immune-mediated gluten-induced enteropathy that affects predisposed individuals of all ages. Many patients with CD do not report gastrointestinal symptoms making it difficult to reach an early diagnosis. On the other hand, CD is related to a wide spectrum of extra-intestinal manifestations, being dermatitis herpetiformis (DH) the best characterized. These associated conditions may be the clue for reaching the diagnosis of CD. Over the last years, there have been multiple reports of the association between CD and several cutaneous manifestations that may improve with a gluten-free diet (GFD). The presence of some of these skin diseases, even in absence of gastrointestinal symptoms, should give rise to an appropriate screening for CD. The aim of this paper is to describe the different cutaneous manifestations that have been associated to CD and the possible mechanisms involved.

IgA vasculitis is a small-vessel vasculitis mediated by immune complexes. In clinical terms, it is characterized by palpable purpura in the lower limbs, joint involvement in the form of arthralgia or arthritis, and gastrointestinal and renal involvement (this will mark a poorer prognosis in adults). Infectious processes, mainly in the upper respiratory tract, are frequently found to be triggers. On the other hand, human immunodeficiency virus (HIV) causes immune dysfunction, which triggers hypergammaglobulinemia and can trigger autoimmune disorders. At times, this can affect the vascular endothelium, giving rise to vasculitic manifestations, although there are few reports in the literature of its role in the presentation of HIV.

del poster presentado: ESMO 21st World Congress on Gastrointestinal Cancer, 03–06 July 2019, Barcelona, Spain.

A bioanalytical method was developed and applied to quantify the free imipenem concentrations for pharmacokinetics and PK/PD correlation studies of the dose adjustments required to maintain antimicrobial effectiveness in pediatric burn patients. A reverse-phase Supelcosil LC18 column (250 x 4.6 mm 5 micra), binary mobile phase consisting of 0.01 M, pH 7.0 phosphate buffer and acetonitrile (99:1, v/v), flow rate of 0.8 mL/min, was applied. The method showed good absolute recovery (above 90%), good linearity (0.25-100.0 µg/mL, r2=0.999), good sensitivity (LLOQ: 0.25 µg/mL; LLOD: 0.12 µg/mL) and acceptable stability. Inter/intraday precision values were 7.3/5.9%, and mean accuracy was 92.9%. A bioanalytical method was applied to quantify free drug concentrations in children with burns. Six pediatric burn patients (median 7.0 years old, 27.5 kg), normal renal function, and 33% total burn surface area were prospectively investigated; inhalation injuries were present in 4/6 (67%) of the patients. Plasma monitoring and PK assessments were performed using a serial blood sample collection for each set, totaling 10 sets. The PK/PD target attained (40%T>MIC) for each minimum inhibitory concentration (MIC: 0.5, 1.0, 2.0, 4.0 mg/L) occurred at a percentage higher than 80% of the sets investigated and 100% after dose adjustment. In conclusion, the purification of plasma samples using an ultrafiltration technique followed by quantification of imipenem plasma measurements using the LC method is quite simple, useful, and requires small volumes for blood sampling. In addition, a small amount of plasma (0.25 mL) is needed to guarantee drug effectiveness in pediatric burn patients. There is also a low risk of neurotoxicity, which is important because pharmacokinetics are unpredictable in these critical patients with severe hospital infection. Finally, the PK/PD target was attained for imipenem in the control of sepsis in pediatric patients with burns. Desenvolveu-se e aplicou-se método bioanalítico para quantificar concentrações de imipenem livre para estudos de farmacocinética (PK) e de correlação PK/PD dos ajustes de dose requeridos para manter a efetividade antimicrobiana em pacientes pediátricos queimados. Utilizou-se coluna Supelcosil LC18 (250 x 4,6 mm 5 micra), fase móvel binária, consistindo de tampão fosfato 0,01M pH 7,0 e acetonitrila (99:1, v/v) e fluxo de 0,8 mL/min. O método mostrou boa recuperação absoluta (acima de 90%), boa linearidade (0,25-100,0 µg/mL, r2=0.999), boa sensibilidade (LLOQ: 0,25 µg/mL; LLOD: 0,12 µg/mL) e estabilidade aceitável. Os valores de precisão inter/intradia foram 7,3/5,9% e a exatidão média foi de 92,9%. O método bioanalítico foi aplicado para quantificar concentrações de fármaco livre em crianças com queimaduras, Seis pacientes pediátricos queimados (idade média de 7,0 anos, 27,5 kg), com função renal normal e 33% da superfície total queimada foram investigados prospectivamente. Lesões por inalação estavam presentes em 4/6 (67%) dos pacientes. O monitoramento plasmático e a as avaliações de PK foram efetuadas utilizando coleção de amostras seriais de sangue para cada série, totalizando 10 conjuntos. O alvo PK/PD alcançado (40%T>MIC) para cada concentração inibitória mínima (MIC: 0,5, 1,0, 2,0, 4,0 mg/L) ocorreu em porcentagem maior do que 80% dos conjuntos investigados e 100% após o ajuste de dose. Em conclusão, a purificação das amostras do plasma usando técnica de ultrafiltração seguida de quantificação das medidas do imipenem no plasma usando método de cromatografia líquida é bastante simples, útil e necessita de pequenos volumes para as amostras de sangue. Além disso, pequena quantidade de plasma (0,25 mL) é necessário para garantir a efetividade do fármaco nos pacientes pediátricos queimados. Há, ainda, baixo risco de neurotoxicidade, o que é importante, visto que as farmacocinéticas são imprevisíveis nesses pacientes críticos, com grave infecção hospitalar. Finalmente, o alvo PK/PD foi alcançado para o imipenem no controle da sepse em pacientes pediátricos com queimaduras.

Metastasis to the skin from carcinoma arising in other organs is uncommon, yet it may be the first presentation of neoplastic disease. The incidence of esophageal adenocarcinoma has been rapidly rising and now accounts for at least half of esophageal carcinomas. Cutaneous metastases of esophageal adenocarcinoma are extremely rare; less than 1 % of patients with metastatic disease have cutaneous involvement. We reported a rare cutaneous cheek metastasis from an adenocarcinoma in an 81-year-old white man, who was excised, and the defect repaired with a reverse cervicofacial flap. Subsequent investigations, based on the result of the pathological anatomy, detected the primary tumor in the esophagus, despite no symptoms. Although cancer of internal organs rarely presents with skin metastases, any suspicious lesions with rapid growth should be ruled out as their metastatic origin. We reported a case and reviewed the clinical characteristics of the few patients reported on the literature.

Highlights • Primary gastric choriocarcinoma is a rare and aggressive tumour with poor prognosis. • It is a β-HCG-producing tumour of trophoblastic cells. • Most (70%) primary gastric choriocarcinomas have an adenocarcinoma component. • Definitive diagnosis is usually made after surgery. • The optimal treatment has not yet been established due to very few reported cases., Introduction Primary gastric choriocarcinoma accounts for 0.08% of all gastric cancers. It is a rapidly growing, widely metastatic and β-HCG-producing tumour of trophoblastic cells. Presentation of case A 69-year-old white man presented to the hospital with symptomatic anaemia. An upper gastrointestinal endoscopy showed an ulcer of the cardia and lesser curvature, whose biopsy specimens proved to be malignant (carcinoma cells, non-specified). The patient underwent total gastrectomy with D2 lymphadenectomy. A histologic evaluation revealed a choriocarcinoma admixed with adenocarcinoma cells without lymph node metastases. The patient died from haemorrhagic shock, due to rupture of liver metastases and a massive haemoperitoneum, within 2 months of the initial presentation. Discussion Primary gastric choriocarcinoma characteristics resemble those of gastric primary adenocarcinoma. The dedifferentiation theory is the most widely accepted theory to explain the pathogenesis of PGC. It is essential to rule out other possible primary lesions such as testicular tumour. The optimal treatment is not yet well established due to very few reported cases. Conclusion Primary gastric choriocarcinoma is a rare tumour with an aggressive behaviour and very poor prognosis.

Genetic factors are involved not only in the overall risk of suffering psoriasis, but also in their clinical characteristics and eventually in drug outcome. Biological therapies have dramatically improved the prognosis of Psoriasis. However, these treatments are very expensive and patients often exhibit a heterogeneous response that could be partially attributed to their genetic background. Thus, the research for genetic markers in psoriatic patients that could predict a poor response to biological therapies is an important issue. Our aim was to evaluate the effect of DNA variants at the “TNFα pathway” that could affect the risk of developing Psoriasis or the response to biological therapies among these patients. The genetic association study included a total of 518 Psoriatic patients and 480 healthy controls. Ninety of these patients received biological treatment and based on the change in the PASI score after 24 weeks were classified as good (PASI score ≥75 %), intermediate (PASI 50–75), and non-responders (PASI

Bruton's tyrosine kinase (Btk) is a member of the Tec family of protein tyrosine kinases involved in B cell development and proliferation in neoplastic human lymphoid tissues. We used immunohistochemistry to evaluate a polyclonal anti-Btk antibody on formalin-fixed paraffin-embedded tissue blocks. The tested samples included normal lymphoid tissues, tissue samples of 395 different lymphomas and 14 malignant lymphoid cell lines. Btk was expressed more often in B cell lymphomas than in T cell lymphomas. This correlated well with the results obtained on B cell lymphoma cell lines, which strongly expressed Btk, in contrast to T cell lymphoma cell lines. More than 60% of myelomas expressed Btk. Among Hodgkin lymphomas, the nodular lymphocyte predominant variant was more often positive (14/16) than the classical variant (6/27). Only one out of three Hodgkin lymphoma-derived cell lines showed a few atypical large cells expressing Btk. Btk represents a useful marker to identify B cell non-Hodgkin lymphomas. Furthermore, Btk might help to distinguish the nodular lymphocyte predominant variant of Hodgkin lymphomas from the classical form. Finally, in view of the recently discovered therapeutic potential of Btk inhibitors in lymphoma, we report the pattern of expression of Btk in a large collection of different types of lymphoma.

The heterogeneous response to anti-TNF biological drugs among Psoriasis (Psor) patients might be explained by gene variants linked to the risk for Psor. Common variants in the CDKAL1 gene have been associated with the risk of developing Psor. Our hypothesis was that these variants could also influence the response to anti-TNFs among Psor-patients. A reduction of at least 75% in the Psoriasis area and severity index (PASI 75) at week 24 was considered a positive response to treatment. A total of 116 patients (78 responders and 38 non-responders) were genotyped for the CDKAL1 rs6908425, rs4712523, rs111739077, and rs77152992 (p.P409L) single nucleotide polymorphisms. Allele and genotype frequencies differed between the two response groups, with the highest difference for the rs6908425: CC homozygotes were significantly more common among responders (72% vs. 45%; p = 0.005; OR = 3.14, 95%CI = 1.40–7.05). In conclusion, our data suggested that CDKAL1 gene variants have a significant effect on the response to anti-TNF therapies among Psor patients. If confirmed on other large cohorts of patients, the genotyping of these variants might help to predict the biological response.

AimsTo investigate the expression of major proteins related to primary neurodegenerative diseases and their prognostic significance in brains with Creutzfeldt-Jakob disease (CJD).Materials and methodsThirty consecutive cases of confirmed CJD during the period 2010–2015 at Basque Brain bank were retrospectively reviewed. Moreover, major neurodegenerative-associated proteins (phosphorylated Tau, 4R tau, 3R tau, alpha-synuclein, TDP43, amyloid beta) were tested. Clinical data were reviewed. Cases were divided according to the presence or absence of copathology. Survival curves were also determined.ResultsCopathology was significantly associated with survival in brains with CJD (4.2±1.2 vs 9.2±1.9; P=0.019) and in brains with MM1/MV1 CJD (2.1±1.0 vs 6.7±2.8; P=0.012). Besides, the presence of more than one major neurodegenerative-associated protein was significantly associated with survival (4.2±1.2 vs 10.7±2.6; P=0.017). Thus, univariate analyses further pointed out variables significantly associated with better survival: copathology in CJD (HR=0.430; P=0.033); more than one neurodegenerative-associated protein in CJD (HR=0.369; P=0.036) and copathology in MM1/MV1 CJD (HR=0.525; P=0.032).ConclusionThe existence of copathology significantly prolongs survival in patients with rapidly progressive dementia due to CJD. The study of major neurodegenerative-associated proteins in brains with CJD could allow us to further understand the molecular mechanisms behind prion diseases.

Rheumatic fever (RF) and rheumatic heart disease (RHD) follow untreated S. pyogenes throat infections in children who present susceptible genes that favor the development of autoimmune reactions. In this review, we focus on the genes that confer susceptibility and on the autoimmune reactions that occur due to molecular mimicry between human-tissue proteins and streptococcal M protein. Polyarthritis is the initial manifestation, which can evolve to carditis and severe valve damage; these culminate in rheumatic heart disease (RHD) or Sydenham's chorea, which affects the central nervous system. A perspective on vaccine development to prevent the disease is also discussed.

Purpose In critical burn patients, the pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare 2 groups of burn patients undergoing treatment for health care–associated infections with and without therapeutic drug monitoring. Methods A retrospective analysis of a clinical intervention (ie, a before/after study) was conducted with patients with health care–associated pneumonia, burn infection, bloodstream infection, and urinary tract infection in the burn intensive care unit of a tertiary care hospital. The patients were divided into 2 groups: (1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimens; and (2) those admitted from November 2008 to June 2011 who received antibiotics (imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according to plasma monitoring and pharmacokinetic modeling. General characteristics of the groups were analyzed, as were clinical outcomes and 14-day and in-hospital mortality. Findings Sixty-three patients formed the conventional treatment group, and 77 comprised the monitored treatment group. The groups were homogeneous, median age was 31 years (range: 1–90) and 66% were male. Improvement occurred in 60% of the patients under monitored treatment (vs 52% with conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital mortality was similar between groups (39% vs 36%). In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area ≥30%, older age, and male sex. Treatment group did not affect the prognosis. Implications Therapeutic drug monitoring of antimicrobial treatment did not alter the prognosis of these burn patients. More trials are needed to support the use of therapeutic drug monitoring to optimize treatment in burn patients.

Summary Objective: To evaluate clinical and epidemiological characteristics and clinical outcomes in patients hospitalized with decompensated heart failure (DHF), with a comparison between Chagas and non-Chagas disease. Method: This is a retrospective cohort study involving 136 patients consecutively admitted with DHF between January 1 and December 31, 2011, with the following outcomes: acute renal failure, cardiogenic shock, rehospitalization, and hospital death. Individuals aged ≥ 18 years with DHF were included while those with more than 10% of missing data regarding outcomes were excluded. Statistical analysis was performed using SPSS version 17.0. Chi-squared test was used to compare proportions. Student's T test was used to compare means. Kaplan-Meier and log-rank tests were used to compare rehospitalization rates between the two groups over time. Results: Chagasic and non-chagasic patients were compared. The first had lower mean systolic blood pressure (111.8±18.4 versus 128.8±24.4, p

Background Common DNA variants in IL12B, IL23R and IL23A have been associated with an increased susceptibility to psoriasis (Ps) and psoriatic arthritis (PsA). Metabolic comorbidities and cardiovascular risk factors have also been associated to both Ps and PsA. Objective To analyze the effect of single nucleotide polymorphisms (SNPs) previously linked to Ps (IL12B rs6887695 and rs3212227, IL23R rs2201841 and rs11209026, and IL23A rs2066808) in the main phenotype and metabolic/cardiovascular characteristics among Ps patients from a Northern Spanish population. Methods The aforementioned genetic variants were determined in a total of 405 chronic plaque Ps patients and 426 controls. Subsequent statistical analysis included stratification for psoriatic clinical characteristics (age of onset, disease severity, familial psoriasis, HLA-Cw6, nail psoriasis) plus diabetes mellitus type 2, arterial hypertension, dyslipidemia and ischemic cardiac events as comorbidities. Results An association between IL23R rs11209026-GG genotype with a more severe disease (p = 0.02, OR = 2.11, 95% CI = 1.13–3.95). Carriers of the IL23A rs2066808-A allele were significantly more frequent among PsA patients (p = 0.016, OR = 3.04, 95% CI = 1.19–7.78). We found significant associations between three SNP genotypes and type 2 diabetes: IL12B rs6887695-CC (p = 0.03, OR = 2.90, 95% CI = 1.09–7.69), IL12B rs3212227-CC (p = 0.035, OR = 5.90, 95% CI = 1.35–25.73) and IL23R rs2201841-GG (p = 0.027, OR = 2.69, 95% CI = 1.09–6.66). Conclusion In our population, genetic variation at IL12B, IL23R and IL23A has an influence not only on the risk for Ps but also on disease severity and type 2 diabetes mellitus.

Merkel cell carcinoma (MCC) is an aggressive uncommon neuroendocrine tumour of the skin, probably originating from Merkel cells, and described by Toker in 1972 as Trabecular carcinoma [1]. Subsequently, electron-dense neurosecretory granules were demonstrated in the tumour cells and it was classified as definite neuroendocrine tumour. Merkel cell carcinoma is characterised by a high incidence of local recurrences, regional local metastases, distant metastasis, and high mortality rate [2]. Merkel cell carcinoma occurs predominantly in elderly white males (61% male vs. 39% female), with a mean age of 69 years at diagnosis [3]. Lately, reports on MCC have increased, probable due to the higher incidence of damaging sun exposure, the advancing age of the population, and the increasing numbers of immunocompromised individuals [3]. In fact, it has been described that MCC is strongly associated with a polyomavirus [4], which might explain why MCC appears more frequently in immunocompromised patients such as solid-organ transplant recipients and HIV/AIDS infected people, and is associated with other malignancies [5]. Taking all of the data together, MCC could sometimes appear as a metastatic tumour in many different organs such as liver, bone, lung, and brain [6]. In light of this we report herein a patient who developed anaemia due to gastric haemorrhage as the first sign of gastric metastasis by MCC, which has rarely been reported [7]. A 52-year-old man with a previous diagnosis of type 2 diabetes mellitus and mild retinopathy was referred to our hospital due to severe asthaenia and dizziness. Almost 2 years previously, a cutaneous surgical excision was performed removing a 2 cm well-delimitated solid nodule on his right thigh, diagnosed as a Merkel cell carcinoma after a battery of immunohistochemical tests (Figures 1 A, ​,B).B). Moreover, ipsilateral inguinal lymphadenectomy was done revealing one infiltrated lymph node. The patient underwent local radiotherapy (5000 RADs) in combination with chemotherapy (carboplatin and etopoxide) with a very good clinical tolerance. So far, the patient has been asymptomatic. Figure 1 Histopathological images of the primary and metastatic Merkel cell carcinoma. Haematoxylin and eosin staining of the primary cutaneous MCC (A, 40×; B, 200×) and the gastric metastasize (C, 20×; D, 200×) show an infiltrative ... The current physical examination of the patient pointed out a paleness of the skin and mucous membranes. An extensive workup was performed showing intense anaemia with haemoglobin level of 8.4 g/dl. Abdominal computed tomography (CT) highlighted a gastric wall thickening with associated regional lymphadenopathy. Subsequently, gastroscopy showed a bleeding, ulcerated lesion measuring 2 cm in diameter, with irregular borders and presented at minor curvature of the stomach. Biopsies were taken from the lesion and studied in the Pathology Department. Microscopic examination of the gastric ulcer showed an gastric mucosa infiltrated by small cells with uniform hyperchromatic nuclei with “salt and pepper” chromatin (Figures 1 C, ​,D).D). Immunohistochemically, these cells were positive for cytokeratin 8, cytokeratin 20 (dot-like pattern), neuron-specific enolase, synaptophysin, and chromogranin A (Figures 1 E, ​,F).F). Ki-67 proliferation index was about 50%. The tumour cells were negative for CK7, TTF1, S100, CD45, and CD99. Moreover, a previous surgical skin biopsy diagnosed as MCC almost 2 years ago was fully revised, pointing out the same histological appearances and immunohistochemistry expressions. Finally, these clinical, radiological, and pathological findings were consistent with an ulcerative metastatic MCC in the stomach. The patient was transfused with two red blood cell concentrates and oral iron. Even though he received chemotherapy again, he passed away 6 months after admission. Merkel cell carcinoma is an rare neuroendocrine tumour of the skin that occurs predominantly in the head and neck (41% to 50%), followed by the extremities (32% to 38%) and trunk (12% to 14%), mainly in elderly white males [3]. This neoplasm usually presents as a rapidly growing, dome-shaped red or bluish nodule. However, sometimes it can adopt a plaque-like appearance with small satellite lesions. Thus, due to its rareness and heterogeneous clinical appearance, it is hardly ever thought of as a primary diagnosis, so definite diagnosis is often established only after biopsy [8]. Therefore, on H + E, microscopic appearances are consistent with highly proliferative cells of uniform small round cell with atypical features that could be easily confused with lymphoma, leukaemia, metastatic small cell carcinoma of the lung, melanoma, and other poorly differentiated cutaneous malignancies [9]. However, MCC presents a few microscopic clues that could help us to make an accurate diagnosis, such as pseudorosettes or a rounded irregular nucleus with condensed and uniformly dispersed nuclear chromatin, without the presence of any nucleoli. Immunohistochemically, the tumour cells are mainly characterised by their positive expression for neuroendocrine markers such as synaptophysin and chromogranin, with a characteristic diagnostic feature of a cytoplasmic dot-like staining pattern for cytokeratin 20 [10]. Moreover, negativity for CK7, TTF1, S100, CD45, and CD99 excluded other differential diagnosis, such as metastatic small cell carcinoma of the lung, melanoma, lymphoma, or primitive neuro-ectodermal tumours, respectively. None of the plasma hormone levels was elevated, considering the remote possibility of a primary neuroendocrine tumour of the stomach. Merkel cell carcinoma is an aggressive tumour characterised by high incidence of local recurrences of regional local metastases and distant metastasis. In fact, the most common sites of distant metastasis are distant lymph nodes (27–60%), distant skin (9–30%), lung (10–23%), central nervous system (18%), and bone (15%) [11]. Merkel cell carcinoma rarely metastasises to the stomach. However, a few cases have been reported in the literature with an interesting recent study performed by Syal et al., pointing out that up to 80% of patients with gastric metastasis of MCC presented with upper gastrointestinal bleeding consistent with the presented case [12]. Furthermore, they also noted that the mean time between upper gastrointestinal bleeding due to a metastatic MCC and death is about 4 months [12], slightly less than the 6-month survival observed in our patient. In conclusion, MCC is an aggressive skin tumour that hardly ever metastasises to the stomach, giving rise to a fatal outcome. Immunohistochemical studies play an important role in the diagnosis, in order to rule out more frequent gastric malignancies. An interdisciplinary approach is recommended in the management of this rare tumour.

Individual age is a key parameter when studying population dynamics of a species. However, accurate age determination in bivalve shells is not always straightforward due to the difficulty of using external growth lines on the shell surface as a reliable method to identify annual growth patterns. In the present paper, we aimed at validating the seasonality in growth lines in the shell of Macoma balthica using stable oxygen and carbon isotopes (delta O-18 and delta C-13) as well as trace elements (Sr, Mn, Mg and Ca).During a 1-year growth experiment, delta O-18 values in the shell carbonate peaked in February/March and matched the annual line visible in the acetate peel of the shell's cross-section. Most carbonate was deposited in the months March to May, which was supported by the observed fast growth in the experiment during this period. Growth stopped between October and December indicating that annual growth lines are formed due to autumn growth stop. Fast growth occurs mainly at temperatures above 6-7 degrees C, although growth may already start at temperatures of about 5 degrees C.delta C-13 profiles did not show any clear seasonality related to the position of the growth lines on the valve or acetate peel and, therefore, cannot be used to estimate age. Along the hinge, Sr was the only element showing variation on the growth lines. High Sr/Ca ratios in the hinge occurred near annual growth lines identified in the acetate peel, suggesting that Sr/Ca ratios may be used to identify annual growth lines and estimate age in M. balthica. Furthermore, counting external lines (on the valve) always lead to an overestimation of age and thus an underestimation of annual growth rates. Therefore, an analysis of the cross-section of the valve seems necessary to accurately estimate age and growth rate in this species. This aspect should be taken into account in studies of growth and population dynamics.

Epithelioid angiosarcomas are rare malignant mesenchymal tumors. The main problem of these tumors is the complicate clinical and histological diagnosis. We report a case with an immunohistochemical panel. We propose the use of CD31 in the immunohistochemical panel of an undifferenciated tumor with epithelioid features, because it appears to be the only endothelial marker these tumors constantly express.

Background Several studies stated that patient with psoriasis carried an increased risk of psoriasis but some studies did not demonstrate this association. Objectives The aim of this study was to evaluate the prevalence of hypertension in psoriasis based on a sample of Spanish population. Methods This was a hospital-based case-control study involving 661 psoriatic patients (cases) and 661 control matched by gender and age. Meta-analysis of the previous studies was made. Results The prevalence of hypertension was significantly higher in psoriasis patients than controls (30.3%, 21.3%, respectively, P

Nitric oxide (NO) is a potent regulator of keratinocyte growth and differentiation that has been implicated in the pathogenesis of psoriasis (Ps). The NOS3 −786 T/C (SNP id rs2070744; http://www.ensembl.org), intron 4 variable number tandem repeat (VNTR), and Glu298Asp (SNP id rs1799983) polymorphisms, have been associated with differences in NO plasma concentrations and with the risk of hypertension (HT) and ischemic cardiac disease. The aim of this study was to determine whether the above-mentioned NOS3 variants contributed to the risk of Ps, and were associated with the risk for HT and CAD in these patients. A total of 368 patients with chronic plaque Ps and 400 healthy controls were genotyped for the NOS3 −786 T/C, intron 4 VNTR, and Glu298Asp polymorphisms. Carriers of the −786 C allele were significantly more frequent among the patients (p < 0.001). Carriers of the 4-repeats allele (45 + 44 genotypes) were also more frequent a (p < 0.001). No significant difference was found for the Glu298Asp polymorphism. None of the NOS3 variants was associated with Ht and CAD in our population. In conclusion, NOS3 gene polymorphism would be risk factors for developing Ps.

OBJETIVOS: Identificar os sorotipos de pneumococo mais frequentemente isolados de crianças internadas com pneumonia invasiva, comparar os sorotipos com os incluídos em vacinas conjugadas e analisar sua sensibilidade aos antimicrobianos mais utilizados na faixa etária pediátrica. MÉTODOS: Estudo descritivo, retrospectivo das pneumonias pneumocócicas identificadas em crianças internadas no hospital universitário da Universidade de São Paulo, no período de janeiro de 2003 a outubro de 2008. Os critérios de inclusão foram: faixa etária de 29 dias até 15 anos incompletos com diagnóstico clínico e radiológico de pneumonia e com cultura de sangue e/ou líquido pleural com crescimento de Streptococcus pneumoniae. RESULTADOS: Foram incluídas no estudo 107 crianças. Os sorotipos mais frequentes foram: 14 (36,5%), 1 (16,7%), 5 (14,6%), 6B (6,3%) e 3 (4,2%). A proporção de sorotipos contidos na vacina conjugada heptavalente seria de 53,1%, na vacina 10-valente de 86,5% e na 13-valente seria de 96,9%. De acordo com os padrões do Clinical and Laboratory Standards Institute 2008, 100 cepas (93,5%) de pneumococos foram sensíveis à penicilina (concentração inibitória mínima, CIM < 2 µg/mL), 7 cepas (6,5%) com resistência intermediária (CIM = 4 µg/mL) e nenhuma com resistência (CIM > 8 µg/mL). Verificamos alta taxa de sensibilidade para as cepas testadas para vancomicina, rifampicina, ceftriaxone, clindamicina, cloranfenicol e eritromicina. CONCLUSÕES: Nossos resultados confirmam um expressivo impacto potencial das vacinas conjugadas, principalmente pela 10-valente e 13-valente, sobre os casos de pneumonias invasivas. Os resultados de sensibilidade à penicilina evidenciam que a opção terapêutica de escolha para o tratamento das pneumonias invasivas continua sendo a penicilina. OBJECTIVES: To identify the most common pneumococcal serotypes in children hospitalized with invasive pneumonia, correlate isolated serotypes with those included in conjugate vaccines, and ascertain the sensitivity of the isolated pneumococcal strains to penicillin and other antibiotics. METHODS: From January 2003 to October 2008, a retrospective study of hospitalized children with a diagnosis of Streptococcus pneumoniae pneumonia was conducted at the university hospital of Universidade de São Paulo. Criteria for inclusion were: age greater than 29 days and less than 15 years, radiological and clinical diagnosis of pneumonia, and isolation of Streptococcus pneumoniae in blood cultures and/or pleural effusion. RESULTS: The study included 107 children. The most common serotypes were 14 (36.5%), 1 (16%), 5 (14.6%), 6B (6.3%) and 3 (4.2%). The proportion of identified serotypes contained in the heptavalent, 10-valent and 13-valent conjugate vaccines was 53.1, 86.5, and 96.9%, respectively. Pneumococcal strains were sensitive to penicillin (minimum inhibitory concentration, MIC < 2 µg/mL) in 100 cases (93.5%) and displayed intermediate resistance (MIC = 4 µg/mL) in 7 cases (6.5%). No strains were penicillin-resistant (MIC > 8 µg/mL) according to the Clinical and Laboratory Standards Institute 2008 standards. Tested isolates were highly sensitive to vancomycin, rifampicin, ceftriaxone, clindamycin, erythromycin, and chloramphenicol. CONCLUSIONS: Our results confirm a significant potential impact of conjugate vaccines, mainly 10-valent and 13-valent, on invasive pneumonia. Furthermore, susceptibility testing results show that penicillin is still the treatment of choice for invasive pneumonia in our setting.

Data on the potential influence of the angiotensin-converting enzyme (ACE) insertion/ deletion (I/D) genotype on psoriasis are contradictory. Our aim was to investigate the relationship between the ACE gene I/D polymorphism and psoriasis/psoriatic arthritis. To investigate this, a genetic association study was conducted among 268 unrelated patients with psoriasis and 272 controls. The distribution of DD, ID, and II genotypes did not significantly differ between psoriatic patients and controls (DD: 39.6% vs. 34.2%; ID: 46.3% vs. 53.3%; II: 14.1% vs. 12.5%). In conclusion, the ACE polymorphism is not likely to be associated with either psoriasis or psoriatic arthritis in this study.

PURPOSE: Cardiopulmonary bypass is known to alter propofol pharmacokinetics in patients undergoing cardiac surgery. However, few studies have evaluated the impact of these alterations on postoperative pharmacodynamics. This study was designed to test the hypothesis that changes in propofol pharmacokinetics increase hypnotic effects after cardiopulmonary bypass. METHODS: Twenty patients scheduled for on-pump coronary artery bypass graft (group, n=10) or off-pump coronary artery bypass graft (group, n=10) coronary artery bypass grafts were anesthetized with sufentanil and a propofol target controlled infusion (2.0 µg/mL). Depth of hypnosis was monitored using the bispectral index. Blood samples were collected from the induction of anesthesia up to 12 hours after the end of propofol infusion, at predetermined intervals. Plasma propofol concentrations were measured using high-performance liquid chromatography, followed by a non-compartmental propofol pharmacokinetic analysis. Data were analyzed using ANOVA, considering p