Clinical usefulness of B-type natriuretic peptide in the diagnosis of pleural effusions due to heart failure

Background and objective: Light`s criteria are frequently used to evaluate the exudative or transudative nature of pleural effusions. However, misclassification resulting from the use of Light`s criteria has been reported, especially in the setting of diuretic use in patients with heart failure (HF). The objective of this study was to evaluate the utility of B-type natriuretic peptide (BNP) measurements as a diagnostic tool for determining the cardiac aetiology of pleural effusions. Methods: Patients with pleural effusions attributable to HF (n = 34), hepatic hydrothorax (n = 10), pleural effusions due to cancer (n = 21) and pleural effusions due to tuberculosis (n = 12) were studied. Diagnostic thoracentesis was performed for all 77 patients. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic accuracy of plasma BNP and pleural fluid BNP for the prediction of HF. Results: The areas under the ROC curves were 0.987 (95% CI 0.93-0.998) for plasma BNP and 0.949 (95% CI 0.874-0.986) for pleural fluid BNP, for distinguishing between patients with pleural effusions caused by HF (n = 34) and those with pleural effusions attributable to other causes (n = 43). The cut-off concentrations with the highest diagnostic accuracy for the diagnosis of HF as the cause of pleural effusion were 132 pg/mL for plasma BNP (sensitivity 97.1%, specificity 97.4%) and 127 pg/mL for pleural fluid BNP (sensitivity 97.1%, specificity 87.8%). Conclusions: In patients with pleural effusions of suspected cardiac origin, measurements of BNP in plasma and pleural fluid may be useful for the diagnosis of HF as the underlying cause.

Exploring the role of O-Mannosylation in the modulation of E-Cadherin function in Gastric Cancer cell line models

Dissertação de mestrado em Bioquímica Aplicada – Biomedicina

The v-y latissimus dorsi musculocutaneous flap in the reconstruction of large posterior chest wall defects.

Posterior chest wall defects are frequently encountered after excision of tumors as a result of trauma or in the setting of wound dehiscence after spine surgery. Various pedicled fasciocutaneous and musculocutaneous flaps have been described for the coverage of these wounds. The advent of perforator flaps has allowed the preservation of muscle function but their bulk is limited. Musculocutaneous flaps remain widely employed. The trapezius and the latissimus dorsi (LD) flaps have been used extensively for upper and middle posterior chest wounds, respectively. Their bulk allows for obliteration of the dead space in deep wounds. The average width of the LD skin paddle is limited to 10-12 cm if closure of the donor site is expected without skin grafting. In 2001 a modification of the skin paddle design was introduced in order to allow large flaps to be raised without requiring grafts or flaps for donor site closure. This V-Y pattern allows coverage of large anterior chest defects after mastectomy. We have modified this flap to allow its use for posterior chest wall defects. We describe the flap design, its indications, and its limitations with three clinical cases. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266 .

Oxidative stress: a systemic factor implicated in the pathogenesis of hepatic encephalopathy.

Although ammonia is considered the main factor involved in the pathogenesis of hepatic encephalopathy (HE), it correlates well with the severity of HE in acute liver failure, but not in chronic liver disease. Oxidative stress is another factor believed to play a role in the pathogenesis of this syndrome; it represents an imbalance between the production and neutralization of reactive oxygen species, which leads to cellular dysfunction. In the setting of liver disease, oxidative stress represents a systemic phenomenon induced by several mechanisms: decreased antioxidant synthesis, increased systemic release of oxidant enzymes, generation of reactive oxygen species, and impaired neutrophil function. High ammonia concentrations induce cerebral oxidative stress, thus contributing to severe hepatic encephalopathy, as observed in acute liver failure. In chronic liver disease, significantly lower degrees of hyperammonemia (<500 μM) do not induce cerebral nor systemic oxidative stress. Data from both animal and human studies sustain that there is a synergistic effect between systemic oxidative stress, and ammonia that is implicated in the pathogenesis of hepatic encephalopathy.

“So the big rocks we put in the jar”: using situated reasoning to coordinate design activity

Ways in which situated reasoning featured in the course of action in the setting of a pair-programming software design exercise is examined, and how interactionally design was accomplished as a coordinated activity in situ.

Reflexões psicanalíticas winnicottianas sobre o sentido do silêncio no setting

We tried to analyze in this paper the meaning of silence into the analytical setting, based in Winnicott’s proposal of psychoanalysis and from clinical experience fragments of one the authors. Therefore, we surveyed the meaning of silence in the setting for some psychoanalysts and, afterwards, we made reference mainly to the concepts related to Winnicott’s Theory of the Emotional Maturity, such as holding, handling, the presentation of objects, and those concerning hesitation and transitionality. We further availed ourselves of the concepts of transference and count transference to ponder on the therapeutic dyad into the analytical setting. Our final considerations point to the need to consider silence as an important communication in certain circumstances of the therapeutic work, as well as suggesting that the setting, in this case study, requested hopeful non-invasive approach of the therapist, to allow the appearance of transitional space through which the emotional maturity can be resumed in this patient.

In vitro characterisation and expansion of human regulatory T cells for their in vivo application in the induction of tolerance in haematopoietic stem cell and solid organ transplantation

Solid organ transplantation (SOT) is considered the treatment of choice for many end-stage organ diseases. Thus far, short term results are excellent, with patient survival rates greater than 90% one year post-surgery, but there are several problems with the long term acceptance and use of immunosuppressive drugs. Hematopoietic Stem Cells Transplantation (HSCT) concerns the infusion of haematopoietic stem cells to re-establish acquired and congenital disorders of the hematopoietic system. The main side effect is the Graft versus Host Disease (GvHD) where donor T cells can cause pathology involving the damage of host tissues. Patients undergoing acute or chronic GvHD receive immunosuppressive regimen that is responsible for several side effects. The use of immunosuppressive drugs in the setting of SOT and GvHD has markedly reduced the incidence of acute rejection and the tissue damage in GvHD however, the numerous adverse side effects observed boost the development of alternative strategies to improve the long-term outcome. To this effect, the use of CD4+CD25+FOXP3+ regulatory T cells (Treg) as a cellular therapy is an attractive approach for autoimmunity disease, GvHD and limiting immune responses to allograft after transplantation. Treg have a pivotal role in maintaining peripheral immunological tolerance, by preventing autoimmunity and chronic inflammation. Results of my thesis provide the characterization and cell processing of Tregs from healthy controls and patients in waiting list for liver transplantation, followed by the development of an efficient expansion-protocol and the investigation of the impact of the main immunosuppressive drugs on viability, proliferative capacity and function of expanded cells after expansion. The conclusion is that ex vivo expansion is necessary to infuse a high Treg dose and although many other factors in vivo can contribute to the success of Treg therapy, the infusion of Tregs during the administration of the highest dose of immunosuppressants should be carefully considered.

MRI for differentiating ganglion and synovitis in the chronic painful wrist

OBJECTIVE: The purpose of our study was to determine if preoperative MRI can differentiate between occult ganglion and synovitis in the chronic painful wrist. CONCLUSION: MRI is accurate in preoperatively distinguishing between ganglion and synovitis in the setting of chronic dorsal wrist pain. Four main criteria were useful: margin, shape, internal structure, and enhancement after administration of contrast material, with shape and internal structure being most helpful.

Hodgkin lymphoma in the Swiss HIV Cohort Study

Hodgkin lymphoma (HL) risk is elevated among persons infected with HIV (PHIV) and has been suggested to have increased in the era of combined antiretroviral therapy (cART). Among 14,606 PHIV followed more than 20 years in the Swiss HIV Cohort Study (SHCS), determinants of HL were investigated using 2 different approaches, namely, a cohort and nested case-control study, estimating hazard ratios (HRs) and matched odds ratios, respectively. Forty-seven incident HL cases occurred during 84,611 person-years of SHCS follow-up. HL risk was significantly higher among men having sex with men (HR vs intravenous drug users = 2.44, 95% confidence interval [CI], 1.13-5.24) but did not vary by calendar period (HR for 2002-2007 vs 1995 or earlier = 0.65, 95% CI, 0.29-1.44) or cART use (HR vs nonusers = 1.02, 95% CI, 0.53-1.94). HL risk tended to increase with declining CD4(+) cell counts, but these differences were not significant. A lower CD4(+)/CD8(+) ratio at SHCS enrollment or 1 to 2 years before HL diagnosis, however, was significantly associated with increased HL risk. In conclusion, HL risk does not appear to be increasing in recent years or among PHIV using cART in Switzerland, and there was no evidence that HL risk should be increased in the setting of improved immunity.

Melan-a-positive "pseudomelanocytic nests": a pitfall in the histopathologic and immunohistochemical diagnosis of pigmented lesions on sun-damaged skin

We encountered recently 3 cases with a histopathologic diagnosis of melanoma in situ on sun-damaged skin (male = 2, female = 1; median age: 59 years; range: 52-60 years). The diagnosis was based mainly on the finding of actinic elastosis in the dermis and increased number of melanocytes in the epidermis and was confirmed by strong positivity for Melan-A in single cells and in small nests ("pseudomelanocytic nests"), located at the dermoepidermal junction. Indeed, examination of slides stained with hematoxylin and eosin revealed the presence of marked hyperpigmentation and small nests of partially pigmented cells at the dermoepidermal junction, positive for Melan-A. The histologic and especially the immunohistochemical features were indistinguishable from those of melanoma in situ on chronic sun-damaged skin. In addition, a variably dense lichenoid inflammation was present. Clinicopathologic correlation, however, showed, in all patients, the presence of a lichenoid dermatitis (phototoxic reaction, 1 case; lichen planus pigmentosus, 1 case; and pigmented lichenoid keratosis, 1 case). Our cases clearly show the histopathologic pitfalls represented by lichenoid reactions on chronic sun-damaged skin. Immunohistochemical investigations, especially if performed with Melan-A alone, may lead to confusing and potentially disastrous results. The unexpected staining pattern of Melan-A in cases like ours raises concern about the utility of this antibody in the setting of a lichenoid tissue reaction on chronic sun-damaged skin. It should be underlined that pigmented lesions represent a paradigmatic example of how immunohistochemical results should be interpreted carefully and always in conjunction with histologic and clinical features.

Hyperplasia to neoplasia sequence of duodenal and pancreatic neuroendocrine diseases and pseudohyperplasia of the PP-cells in the pancreas.

Hyperplastic changes of the neuroendocrine cell system may have the potential to evolve into neoplastic diseases. This is particularly the case in the setting of genetically determined and hereditary neuroendocrine tumor syndromes such as MEN1. The review discusses the MEN1-associated hyperplasia-neoplasia sequence in the development of gastrinomas in the duodenum and glucagon-producing tumors in the pancreas. It also presents other newly described diseases (e.g., glucagon cell adenomatosis and insulinomatosis) in which the tumors are (or most likely) also preceded by islet cell hyperplasia. Finally, the pseudohyperplasia of PP-rich islets in the pancreatic head is defined as a physiologic condition clearly differing from other hyperplastic-neoplastic neuroendocrine diseases.

Urinary albumin levels in the normal range determine arterial wall thickness in adults with Type 2 diabetes: a FIELD substudy

Aim Cardiovascular disease (CVD) rates are substantially higher among patients with Type 2 diabetes than in the general population. The objective of this study was to identify the determinants of carotid intima media thickness (IMT) in patients with Type 2 diabetes. Methods We measured the thickness of the intima media layer of the carotid artery, a strong predictor of the risk of future vascular events, in 397 Type 2 diabetic patients drawn from the Fenofibrate Intervention and Event Lowering in Diabetes study, prior to treatment allocation. Results The mean IMT was 0.78 mm [interquartile range (IQR) 0.23 mm], and the maximum IMT was 1.17 mm (IQR 0.36 mm). By multivariate analysis, age, sex, duration of diabetes, triglycerides, and total cholesterol were independently correlated with IMT, as was urine albumin-creatinine ratio (ACR) (P < 0.001). The effect of ACR on IMT was further examined by tertile. Clinically significant differences in IMT were associated with ACR > 0.65 mg/mmol, approximately one-fifth the standard clinical threshold for microalbuminuria (P < 0.01). Long-term diabetes, independent of other parameters, was associated with a 50% increase in age-related thickening. Conclusions IMT in people with Type 2 diabetes is independently and continuously related to urine albumin levels and to the duration of diabetes. These results support previous data linking urine albumin measurements within the normal range with increased ischaemic cardiac mortality in the setting of Type 2 diabetes, and strongly suggest that urine albumin levels within this range should trigger a formal evaluation for CVD.

Recovering Natural History: Modeling Cardiovascular Biomarkers in the Presence of Endogenous Medication Use

Thesis (Ph.D.)--University of Washington, 2016-08

Involving individuals in the manufacturing strategy formation : Strategic consensus among workers and managers

Decisions made and actions taken by individuals in the operations function impact the formation of a company’s manufacturing strategy (MS). Therefore, it is important that the MS is understood and agreed on by all employees, that is, strategic consensus among the individuals in the operations function is essential. This research contributes to the current body of knowledge by including a workers’ perspective on MS formation. It is the workers on the shop floor who bring the MS to life in the actual operations through their daily decisions and actions. The MS falls short if the priorities outlined do not materialise in practice as intended. The purpose of this research is to investigate how the individuals in the operations function perceive the MS in order to understand how these individuals are involved in the MS formation. The research is based on five studies, differing by evidence, as follows: one theoretical, three qualitative in the setting of small and medium-sized enterprises (SMEs), and one quantitative at a large company. Based on the findings presented in the six appended papers, the results show that empirically and conceptually, workers have been overlooked or given a passive role in the MS formation. Empirically, it is seen that workers and managers do not have a shared understanding of the underlying reasons for strategic priorities; hence, the level of strategic consensus is low. Furthermore, the level of strategic consensus varies among the different MS dimensions depending on their organisational level. Moreover, the empirical findings reveal that internal contextual factors influence the individuals’ perceptions of the MS and the possibilities for strategic consensus. Regarding the external context, the results show that major customers’ strategies influence the subcontractor SMEs’ MS formation. The usage of means of communication in the operations function has also shown to be of importance for how the MS is perceived. Conceptually, the findings indicate that the MS literature tends to treat individuals in the operations function in a deterministic manner; individuals on the shop floor are regarded as manufacturing resources. To ensure a successful MS formation process, where the patterns of the decisions made by the individuals in the operations function forms the MS, the view on human nature within the MS requires a more voluntaristic approach. This research suggests to view the MS formation as an iterative “patterning process” which builds on a reciprocal relationship between workers and managers. The introduction of the patterning process contributes to the research on MS formation by explaining the perception range within the hierarchical levels, by re-defining the hierarchical levels included in the MS formation and by detailing the activities in the MS formation.

Use of closed systems in the Hospital Pharmacy

Objective: In the setting of the increasing use of closed systems for reconstitution and preparation of these drugs, we intend to analyze the correct use of these systems in the Hospital Pharmacy, with the objective to minimize the risks of exposure not only for those professionals directly involved, but also for all the staff in the unit, taking also into account efficiency criteria. Method: Since some systems protect against aerosol formation but not from vapours, we decided to review which cytostatics should be prepared using an awl with an air inlet valve, in order to implement a new working procedure. We reviewed the formulations available in our hospital, with the following criteria: method of administration, excipients, and potential hazard for the staff handling them. We measured the diameters of the vials. We selected drugs with Level 1 Risk and also those including alcohol-based excipients, which could generate vapours. Outcomes: Out of the 66 reviewed formulations, we concluded that 11 drugs should be reconstituted with this type of awl: busulfan, cabazitaxel, carmustine, cyclophosphamide, eribulin, etoposide, fotemustine, melphalan, paclitaxel, temsirolimus and thiotepa; these represented an 18% of the total volume of formulations. Conclusions: The selection of healthcare products must be done at the Hospital Pharmacy, because the use of a system with an air valve inlet only for those drugs selected led to an outcome of savings and a more efficient use of materials. In our experience, we confirmed that the use of the needle could only be avoided when the awl could adapt to the different formulations of cytostatics, and this is only possible when different types of awls are available. Besides, connections were only really closed when a single awl was used for each vial. The change in working methodology when handling these drugs, as a result of this study, will allow us to start different studies about environmental contamination as a future line of work.