Early resuscitation of septic shock patients reduces the sepsis-related morbidity and mortality. The main goals of septic shock resuscitation include volemic expansion, maintenance of adequate tissue perfusion and oxygen delivery, guided by central venous pressure, mean arterial pressure, mixed or central venous oxygen saturation and arterial lactate levels. An aggressive fluid resuscitation, possibly in association with vasopressors, inotropes and red blood cell concentrate transfusion may be necessary to achieve those hemodynamic goals. Nonetheless, even though fluid administration is one of the most common interventions offered to critically ill patients, the most appropriate type of fluid to be used remains controversial. According to recently published clinical trials, crystalloid solutions seem to be the most appropriate type of fluids for initial resuscitation of septic shock patients. Balanced crystalloids have theoretical advantages over the classic solutions, but there is not enough evidence to indicate it as first-line treatment. Additionally, when large amounts of fluids are necessary to restore the hemodynamic stability, albumin solutions may be a safe and effective alternative. Hydroxyethyl starches solutions must be avoided in septic patients due to the increased risk of acute renal failure, increased need for renal replacement therapy and increased mortality. Our objective was to present a narrative review of the literature regarding the major types of fluids and their main drawbacks in the initial resuscitation of the septic shock patients.

Summary This work presents the results of a 4D feasibility study performed with a synthetic carbonate reservoir model based on a pre-salt reservoir. We modeled one base survey and the first monitor acquired after 1.5 years of the first oil. We could observe strong 4D signals related to pore pressure increase due to the injector wells , as well as water and gas saturation changes around the WAG wells. Besides the results of the forward modeling, we also present the results of a 4D seismic inversion applied to the synthetic seismic amplitudes to discuss the complexities of 4D seismic interpretation as well as to check that most of the 4D changes on acoustic impedance can be recovered even with complex time-lapse amplitude data. We also highlight a region of the reservoir from which the 4D signal could be compromised by the presence of a volcanic rock nearby injector wells with intense production activity.

We report a case of disseminated infection by Rhodococcus equi as the inaugural manifestation of idiopathic T-CD4+ lymphopenia. We aim to demonstrate our diagnostic and therapeutic approach and focus on the major dilemmas arising from the lack of scientific evidence regarding best clinical practice of this infection in humans.

Objective: The main aim of the study was to evaluate the efficacy and safety profile of Nivolumab, an immune-checkpoint-inhibitor antibody, in advanced, previously treated, Non-Small Cell Lung Cancer (NSCLC) patients, in a real world setting. Methods: We performed a retrospective, multicentre data analysis of patients who were included in the Portuguese Nivolumab Expanded Access Program (EAP). Eligibility criteria included histologically or citologically confirmed NSCLC, stage IIIB and IV, evaluable disease, sufficient organ function and at least one prior line of chemotherapy. The endpoints included Overall Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS). Safety analysis was performed with the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and immune-related Adverse Events (irAEs) were treated according to protocol treatment guidelines. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Data was analysed using SPSS, version 21.0 (IBM Statistics). Results: From June 2015 to December 2016, a total of 229 patients with advanced NSCLC were enrolled at 30 Portuguese centres. Clinical data were collected up to the end of July 2018. The baseline median age was 64 years (range 37-83) and the majority of patients were males (70.3%) and former/current smokers (69.4%). Patients with non-squamous histology predominated (88.1%), and 67.6% of the patients had received 2 or more prior lines of chemotherapy. Out of 229 patients, data was available for 219 patients (3 patients did not start treatment, while data was unavailable in 7 patients); of the 219 patients, 15.5% were not evaluated for radiological tumour assessment, 1.4% had complete response (CR), 21% partial response (PR), 31% stable disease (SD) and 31.1% progressive disease (PD). Thus, the ORR was 22.4% and DCR was 53.4% in this population. At the time of survival analysis the median PFS was 4.91 months (95% CI, 3.89-6.11) and median OS was 13.21 months (95% CI, 9.89-16.53). The safety profile was in line with clinical trial data. Conclusions: Efficacy and safety results observed in this retrospective analysis were consistent with observations reported in clinical trials and from other centres. (C) 2019 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L.U.

Sepsis is a life-threatening condition which may arise from an extreme response of the body to an infection. While worldwide figures are unknown, it is estimated that sepsis causes millions of yearly fatalities. In this context, it is important to develop tools for decision support and training of healthcare professionals. This paper proposes that artificial intelligence tools be used for prognosis of septic patients. The model used is a neural network trained and validated with cross-validation. The information used includes data regarding patient history and treatment. More importantly, this paper also presents a principled approach of using sensitivity analysis for the identification of discriminatory variables when these are of mixed types such as binary, categorical, and integer. While initial results, validated on over 5000 patients, already show both specificity and sensitivity above 80% and good model robustness against errors in most inputs, even better performance is attained through the utilization of sensitivity analysis to select the variables used as inputs. This work presents a promising tool for input selection in contexts of limited data availability, and successfully applies this technique to obtain a high-performance model for prognosis of septic patients.

Objectives: To quantify the operational costs of a municipal public hospital in the city of São Paulo (Brazil) and to identify factors that led to cost increases during the year of 2016 using the absorption method. Methods: This was a retrospective study conducted between January and December of 2016 at Vila Santa Catarina Municipal Hospital, a public tertiary hospital in São Paulo, Brazil. Results: We identified and analyzed a total of 8702 inpatient data. Average day cost per patient was US$ 949, with a median of US$ 1,825, and a total operating cost of US$ 48,743,847. Transplant patients showed the highest median costs, while pregnant women had the lowest median costs, 69.9% of the 8,702 hospitalized patients was above the mean cost of US$ 3,068 registered for 2016. Age was associated with a 6.6% increase in cost for each one-year increase in age, while the cost associated with female patients was 1.1 times that of men. Patients who died in the hospital were 8 times more likely to cost more than patients who were discharged from the hospital. Oncology, transplant, and clinical-surgical patients had 18.8 times the cost of patients in the maternity unit, respectively. Conclusion: We identify the operating costs of the Vila Santa Catarina Municipal Hospital, where the average cost for the operation of the unit was US$ 133.179. The cost per patient was US$ 1,825.91. We also concluded as to the second objective that the cost increase factors were age and death.

A major challenge for hospitals in low-income and middle-income countries is to improve management of patients diagnosed with sepsis. The objective of the present study was to evaluate the Institute for Healthcare Improvement (IHI) Model as a strategy to implement a managed sepsis protocol aimed at reducing sepsis mortality. We performed a longitudinal, prospective, non-randomised study using PDSA cycles for translating and implementing improvement actions and tools. Baseline case mortality/case fatality data were collected, and compliance rates were evaluated according to the Surviving Sepsis Campaign guidelines (3-hour care-bundle). Sepsis multidisciplinary work teams were designated and were responsible to develop Driver Diagrams and implement process changes in the intensive care unit, wards and emergency department. Satisfaction levels of healthcare professionals were assessed (balance variables). The study was carried out in a public quaternary hospital, in São Paulo city, Brazil (Hospital Municipal da Vila Santa Catarina). The number of patients with sepsis studied was 416 who were followed over a 15-month period. The data analyses were carried out by statistical process control. Case fatality rates were kept below a prespecified target of 25% (15.9%) during the period. Satisfaction level of the participating staff was high (95.2%) and 71% of participants reported no work overload. The IHI model was found to be a feasible and useful strategy for implementing a sepsis management clinical protocol.

To explore the current and past methods used to account for patient-level costs in hospitals. Literature search was performed using Medline (by PubMed), Scopus and Web of Science databases. We only included studies which assessed individual patient’s cost during an entire hospital admission. Exclusions criteria was studies which only estimated patients’ costs; only calculated mean patients’ costs; only assessed costs of a single condition, a single intervention or evaluated only few hospital’s department. From a total of 1,813 studies, only eight fulfilled inclusion criteria and presented no exclusion criteria. Five different costing methods were employed: Absorption Costing Method in four of them; Activity-Based Costing and Cost-to-Charge Ratios were used in two studies; Relative Value Units and Economic Costing in just one study - in two studies two methods were applied simultaneously. Patient-level costs from the hospital perspective is less explored than other perspectives. Most of hospitals analyzed were large and, in general, the applied costing methods were poorly described (especially related on how personnel, material, medicines and depreciation costs were measured and allocated per patient). A hospital can obtain the cost of each patient, regardless of type (public, private or non-profit), size (small, medium or large) and location (developed or developing country), but the costing process can be challenging, because some hospital departments may not record information with the necessary detail, systems can be expensive and a large volume of records require checking, validations and investigations. Despite of patient-level costs are part of the Value-based Healthcare equation, and hospitals costs are usually one of the highest in the healthcare chain, literature is scarce on this subject. More studies on this setting are urgent and should be fostered.

Acute brain lesions constitute an alarming public health concern. Neuroprotective therapies have been implemented to stabilize, prevent, or reduce brain lesions, thus improving neurological outcomes and survival rates. Hypothermia is the most effective approach, mainly attributed to the reduction in cellular metabolic activity. Whole-body cooling is currently implemented by healthcare professionals; however, adverse events are frequent, limiting the potential benefits of therapeutic hypothermia. Therefore, selective methods have been developed to reduce adverse events while delivering neuroprotection. Nasopharyngeal approaches are the safest and most effective methods currently considered. Our primary objective was to determine the effects of a novel nasopharyngeal catheter on the brain temperature of pigs. In this prospective, non-randomized, interventional experimental trial, 10 crossbred pigs underwent nasopharyngeal cooling for 60 min followed by 15 min of rewarming. Nasopharyngeal catheters were inserted into the left nostril and properly positioned at the nasopharyngeal cavity. Nasopharyngeal cooling was associated with a decrease in brain temperature, which was more significant in the left cerebral hemisphere (p = 0.01). There was a reduction of 1.47 ± 0.86 °C in the first 5 min (p < 0.001), 2.45 ± 1.03 °C within 10 min (p < 0.001), and 4.45 ± 1.36 °C after 1 h (p < 0.001). The brain-core gradient was 4.57 ± 0.87 °C (p < 0.001). Rectal, esophageal, and pulmonary artery temperatures and brain and systemic hemodynamic parameters, remained stable during the procedure. Following brain cooling, values of oxygen partial pressure in brain tissue significantly decreased. No mucosal lesions were detected during nasal, pharyngeal, or oral inspection after nasopharyngeal catheter removal. In this study, a novel nasopharyngeal cooling catheter effectively induced and maintained exclusive brain cooling when combined with effective counter-warming methods. Exclusive brain cooling was safe with no device-related local or systemic complications and may be desired in selected patient populations.

Calcular el costo domiciliario de los pacientes con altas tempranas dentro de una red integral en salud. A través de una base de datos de consumo de servicios domiciliarios y hospitalarios del segundo semestre del 2018, reportados por una red integral de salud en Colombia, se identifica la fecha de inicio del consumo domiciliario y se compara con la fecha del egreso hospitalario, aquellos consumos domiciliarios reportados dentro de los 8 días posteriores a la estancia hospitalaria son definidos como altas tempranas. Solo se consideraron pacientes no crónicos que fueron definidos, como pacientes que no presentan consumo de servicios domiciliarios previo a una estancia hospitalaria. El costo promedio de un día de hospitalización domiciliaria para un paciente no crónico es de COP $45.600 (95% IC COP $35.712 – COP $55.536). Los días promedio del evento de la hospitalización domiciliaria son 7,5 días (95% IC 6.4 – 8.6) resultando en un costo promedio evento de hospitalización domiciliaria de COP $342.000. El costo evento domiciliario promedio de un paciente no crónico con alta temprana es de COP $342.000, que es considera muy por debajo del costo hospitalario promedio.

Leiomyoma is the most common benign uterine tumor. Atypically, it can show with metastatic disease. Lungs are the most frequent metastatic site. Although the benign, metastatic leiomyoma (MLM) has an indolent growth pattern and it may induce pulmonary symptoms and decrease the quality of life. We present a case of a 63-year-old woman, former smoker with a past medical history of hysterectomy and bilateral salpingo-oophorectomy due to leiomyoma in 1994. In 2015, the patient showed with a dry cough, chest pain and no fever. Chest X-ray revealed multiple non-specific bilateral pulmonary nodules. Chest and total abdominal CT scans were performed for further evaluation, which confirmed multiple well-circumscribed bilateral pulmonary nodules measuring up to 26mm and 31mm in the right and left lung respectively. No other suspected neoplastic lesions were found. Afterward, she underwent a thoracoscopic resection and pathology determined the neoplastic proliferation of smooth cells favoring the diagnosis of MLM. Tumor markers, including CEA, CA 19.9, CA 125, CA 15.3 and AFP were regular. Patient’s symptoms have improved, and she has started a clinical follow-up alternating chest X-ray with chest CT scan every six months. Four years later, lung nodules have increased, measuring up to 37mm (Figure 1). She underwent a lung CT scan-guided biopsy and final pathology showed mesenchymal neoplasia of smooth muscle cells, with a proliferation of spindle cells, with no atypia, absence of necrosis and mitoses. Positive immunohistochemical staining for desmin and smooth muscle actin positive with negative staining for CD34, S100 protein and DOG 1 (Figure 2). She remains asymptomatic, and the medical oncology team decided to maintain clinical follow-up with a chest CT scan. Despite the increase of the lesion, the patient was asymptomatic and maintained a follow-up in our service. Although MLM is a rare condition, it should be considered in the differential diagnosis in women with a past medical history of uterine leiomyoma. Accurate histopathological and immunochemistry analysis are necessary for the final diagnosis. Due to the slow growth of pattern, most of the patients can be followed with no active specific treatment. There are few similar cases described in the literature and the is no standard treatment in this scenario. Further studies are warranted to evaluate the best treatment option for these patients.

Microvascular dysfunction has been associated with adverse outcomes in critically ill patients, and the current concept of hemodynamic incoherence has gained attention. Our objective was to perform a comprehensive analysis of microcirculatory perfusion parameters and to investigate the best variables that could discriminate patients with and without circulatory shock during early intensive care unit (ICU) admission. This prospective observational study comprised a sample of 40 adult patients with and without circulatory shock (n = 20, each) admitted to the ICU within 24 h. Peripheral clinical [capillary refill time (CRT), peripheral perfusion index (PPI), skin-temperature gradient (Tskin-diff)] and laboratory [arterial lactate and base excess (BE)] perfusion parameters, in addition to near-infrared spectroscopy (NIRS)-derived variables were simultaneously assessed. While lactate, BE, CRT, PPI and Tskin-diff did not differ significantly between the groups, shock patients had lower baseline tissue oxygen saturation (StO(2)) [81 (76-83) % vs. 86 (76-90) %, p = 0.044], lower StO(2)min [50 (47-57) % vs. 55 (53-65) %, p = 0.038] and lower StO(2)max [87 (80-92) % vs. 93 (90-95) %, p = 0.017] than patients without shock. Additionally, dynamic NIRS variables [recovery time (r = 0.56, p = 0.010), descending slope (r = - 0.44, p = 0.05) and ascending slope (r = - 0.54, p = 0.014)] and not static variable [baseline StO(2) (r = - 0.24, p = 0.28)] exhibited a significant correlation with the administered dose of norepinephrine. In our study with critically ill patients assessed within the first twenty-four hours of ICU admission, among the perfusion parameters, only NIRS-derived parameters could discriminate patients with and without shock.

Sepsis is a life-threatening response of the body to infection that often leads to death. In Brazil, hundreds of thousands of deaths occur every year, with a mortality rate higher than the world average. In this context, it is important to develop tools for decision support and training of healthcare professionals. This work discusses a modelling for sepsis that may be instrumental for achieving such goals. Machine learning is used to train a model for prognosis of outcome of septic patients. The inputs of the model include information about the patient sepsis, previous clinical records and treatment variables. The results show that high accuracy can be achieved and that the network is able to really map patients in two highly distinct groups of risk (survival and fatal outcome), under certain conditions.

ABSTRACT Objective To verify the impact of the Lean Six Sigma methodology in reducing incorrect entries of non-appropriated revenues and expenses. Methods Process for the review and application of the Lean Six Sigma methodology between December 2015 and September 2016, in a high-complexity general hospital in the city of São Paulo (SP). Results A total of 3,756,814 (100%) entries were audited between December 2015 and September 2016. The Sigma level evolved over the course of the process and increased from 3.44 Sigma in December 2015 to 5.92 Sigma in September 2016. Entries classified as non-appropriated revenues and expenses were brought down to 0% at the end of the study. Conclusion The use of the Lean Six Sigma methodology was efficient in reducing incorrect entries, calculating costs, ensuring compliance in rendering of accounts and accurately determining cost-outcome ratios.

Magnesium alloys are important alternatives for structural weight reduction due to their low density and good specific mechanical strength. Among the magnesium alloys, the ZK type exhibits the highest mechanical strength. However, it has limitations on hot working or welding owing to the presence of intermetallics with low melting point and consequently susceptibility to hot crack formation. The addition of rare earths tends to form intermetallics with higher melting points, thus inhibiting the formation of hot cracks, as well as building up thin and dense surface films that improve corrosion resistance. This work studies the addition of 1.5% wt. of mischmetal (Mm) to the ZK60 alloy, and then demonstrates the effects of the casting process with mechanical mixing in the semi-solid state. The alloys produced were: ZK60 and ZK60-1.5 wt%Mm manufactured by conventional casting and rheocast ZK60-1.5 wt%Mm produced with mechanical mixing in the semi-solid state. The casting and cooling methods result in defect-free and chemically homogeneous materials, and the mechanical mixing provides a homogeneous microstructure with globular grains. The mechanical strength was though higher for the 2K60 alloy due to its increased solute content within the Mg-matrix and the smaller quantity of intermetallics that builds up an intermittent network. The Mg7Zn3 intermetallic, which is the main precipitate for ZK60 alloy, has hardness 20% higher than the MgZn2Ce intermetallic that is precipitated with the mischmetal addition and partly removes solute from the Mg-solid solution.