Pacientes com lúpus eritematoso sistêmico e síndrome antifosfolípide secundária possuem números reduzidos de células B CD4+ CD25+ Foxp3+ (células Treg) e células B CD3– CD19+ circulantes

IntroductionCD4+CD25+Foxp3+ regulatory T (Treg) cell depletion has been reported in systemic lupus erythematosus (SLE) and, recently, in primary antiphospholipid syndrome (APS); the issue has not been studied in SLE patients with secondary APS (SLE/APS) so far.ObjectiveTo quantify total lymphocytes, Treg cells, CD3+CD19– T cells and CD3–CD19+ B cells in SLE/APS patients and healthy controls.MethodsCell subtypes underwent immunophenotyping using specific monoclonal antibodies (anti–CD3 CY5, anti–CD4 FITC, anti–CD25, anti–Foxp3, anti–CD19 PE) and flow cytometry.ResultsTwenty–five patients with SLE/APS (mean age 43.5 years, 96% females, 96% caucasians, mean duration of disease 9.87 years, mean SLEDAI 10 ± 5.77) and 25 age and sexmatched controls entered the study. It was realized that the numbers of Treg and CD3– CD19+ B cells were significantly lower in SLE/APS patients than in controls (all p < 0.05). Treg and CD3–CD19+ B cells remained numerically low after controlling (ANCOVA) for percentage of total lymphocytes (p < 0.05). Decreasing levels of circulating Treg and CD3–CD19+ B cells correlated to higher scores of lupus activity (rs = –0.75, p < 0.0001; rs = –0.46, p = 0.021, respectively). Number of Treg cells and CD3–CD19+ B lymphocytes did not significantly differ in users or nonusers of chloroquine, azathioprine and corticosteroids (all p > 0.05).ConclusionsIn this preliminary study, patients with SLE and secondary APS showed depletion of Treg and CD3–CD19+ B cells; decreasing numbers of both subtypes correlated to a higher SLEDAI. Treg cells depletion might contribute to the autoimmune lesion seen in patients with SLE/APS. The reduced number of CD3–CD19+ B cells seen in these patients deserves more studies in order to get further elucidation.     

Growth hormone treatment and risk of recurrence or development of secondary neoplasms in survivors of pediatric brain tumors

Growth hormone (GH) is increasingly used for treatment of pediatric brain tumors. However, controversy remains over its safety. This meta-analysis assessed whether GH treatment was associated with risk of recurrence or development of secondary neoplasm for brain tumors in children. Systematic computerized searches of PubMed and Web of Knowledge were performed. Pooled relative risks (RR) with 95% confidence interval (CI) for recurrence and/or secondary neoplasm in children who were treated with GH versus those who did not receive GH were calculated. Ten studies were included. The pooled recurrence rates were 21.0% and 44.3% in the GH-treated group and non-GH-treated group, respectively. The pooled RR for recurrence was 0.470 (95% CI 0.372–0.593; z = 6.33, p = 0.000). Begg’s test (p = 0.060) and Egger’s test (p = 0.089) suggested there was no significant publication bias. The pooled RR in sensitivity analysis was 0.54 (95% CI 0.37–0.77; z = 3.32, p = 0.001), which showed the result was robust. The pooled RR for secondary neoplasm was 1.838 (95% CI 1.053–3.209; z = 2.14, p = 0.032). Begg’s test (p = 1.000) and Egger’s test (p = 0.553) suggested there was no significant publication bias. We found no evidence that GH therapy is associated with an increased risk of recurrence for pediatric brain tumors. However, because of our small sample size, the association of GH therapy with an increased risk of secondary neoplasm is uncertain. Further prospective cohorts are needed.     

Adjuvant HPV vaccination for anal cancer prevention in HIV-positive men who have sex with men: The time is now

ImportanceOutcomes of treating high-grade squamous intraepithelial lesions (HSIL), a precursor to anal cancer, remain uncertain. Emerging evidence shows that post HSIL treatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves the effectiveness of treatment. However, no recommendations exist regarding the use of qHPV vaccine as an adjuvant form of therapy. Our objective was to determine whether post-treatment adjuvant vaccination should be adopted in HIV-infected MSM (individuals at highest risk for anal cancer) on the basis of cost-effectiveness determined using existing evidence or whether future research is needed.MethodsWe developed a Markov (state-transition) cohort model to assess the cost-effectiveness of post-treatment adjuvant HPV vaccination of 27 years or older HIV-infected MSM. We first estimated cost-effectiveness and then performed value-of-information (VOI) analysis to determine whether future research is required by estimating the expected value of perfect information (EVPI). We also estimated expected value of partial perfect information (EVPPI) to determine what new evidences should have highest priority.ResultsWith the incremental cost-effectiveness ratio (ICER) of $71,937/QALY, “treatment plus vaccination” was the most cost-effective HSIL management strategy using the willingness-to-pay threshold of 100,000/QALY. We found that population-level EVPI for conducting future clinical research evaluating HSIL management approaches was US$12 million (range $6–$20 million). The EVPPI associated with adjuvant qHPV vaccination efficacy estimated in terms of hazards of decreasing HSIL recurrence was $0 implying that additional data from a future study evaluating efficacy of adjuvant qHPV vaccination will not change our policy conclusion that “treatment plus vaccination” was cost-effective. Both the ICER and EVPI were sensitive to HSIL treatment compliance.ConclusionPost-treatment adjuvant qHPV vaccination in HIV-infected MSM aged 27 or above is likely to be cost-effective. Use of adjuvant qHPV vaccination could be considered as a potential strategy to reduce rising anal cancer burden among these high-risk individuals.     

Identification of a methicillin-resistant Staphylococcus aureus inhibitory compound isolated from Serratia marcescens

In this study, we identified an antimicrobial compound produced by the Gram-negative bacterium Serratia marcescens. Colonies of S. marcescens inhibited the growth of nine different methicillin-resistant Staphylococcus aureus (MRSA) isolates and several other tested Gram-positive bacterial species, but not Gram-negative bacteria. Genetic analysis revealed the requirement for the swrW gene which codes for a non-ribosomal peptide synthetase that generates the cyclodepsipeptide antibiotic serratamolide, also known as serrawettin W1. This is the first report describing the anti-MRSA properties of serratamolide.     

Patient preferences for clinical follow-up after primary treatment for soft tissue sarcoma: A cross-sectional survey and discrete choice experiment

BackgroundPatients treated for soft tissue sarcoma (STS) require long-term follow-up to detect recurrent or metastatic disease, yet marked differences exist in clinical approaches to the length of follow-up, frequency of consultations and investigations undertaken at follow-up visits. There has been no published work assessing patient expectations or the acceptability of post-treatment follow-up strategies. This study aimed to assess the patient acceptability of different follow-up strategies following curative surgery for soft tissue sarcoma and to investigate the hypothetical levels of recurrence risk at which different follow-up regimes were acceptable.MethodsPatients were recruited from the Royal Orthopaedic Hospital in Birmingham. The study used a cross-sectional survey incorporating a best-worst scaling discrete choice experiment to assess patient preferences regarding different aspects of follow-up.Results132 patients participated (47% response). The nature of investigations undertaken during follow-up was the most important aspect of post-surgical care. Patients typically preferred appointments routinely consisting of clinical examination and chest X-ray, and for follow-up to remain in secondary care rather than general practice.ConclusionClear protocols for STS patient follow-up can improve consistency and equity of care. In determining the optimum follow-up plan for STS patients from the patient perspective, this study provides valuable information that should be considered alongside the clinical effectiveness of follow-up strategies to maximise patient outcomes and use NHS resources appropriately.     

Analysis of time intervals related to STEMI management in 2008–2016

IntroductionA modern treatment of patients with ST segment elevation myocardial infarction (STEMI) is based on a rapid primary percutaneous coronary intervention with direct recanalization of the affected coronary artery (dPCI). The outcome of the treatment depends largely on the pre-hospital care management, which can reduce the total ischaemic time and subsequently improve patient's outlook.AimsThe principal aims of this retrospective study were to assess the development of time intervals related to the pre-hospital care and the effect of the mode of transportation to the cathlab (primary vs secondary) on these intervals in patients with acute STEMI treated by primary PCI in 2008, 2010, 2012, 2014 and 2016.MethodsWe have analysed patients with STEMI treated using PCI within 12 h of symptoms onset. In total, 1250 patients were included. To evaluate the development over the last 8 years, uni- and multivariate analyses were used. Categorical variables were analysed using chi-squared tests while continuous variables were analysed using one-way ANOVA and general linear models. The effect of the year and of mode of transportation on time intervals were studied.ResultsThe time intervals did not significantly differ among years with the exception of 2014 where the reason of the deviation was however not related to the quality of the pre-hospital care. The 120 min limit from the first medical contact to unblocking the affected artery (FMCTB) was met in more than 80% patients (80.8), the recommended limit of 90 min in 55.2% of patients. The key factor affecting the total ischaemic time was however the patients’ choice of the mode of transportation – in patients who opted for the primary route of transportation, i.e., called the ambulance, the intervals were significantly shorter (FMCTB on average by 38.2 min and total ischaemic time by 92.9 min). The principal delays were detected in the patients’ delay (103 min inpatients with primary transportation route, 131 in patients with secondary route) as well as, unfortunately, in the intervals between reporting the patients’ problem to the system and ECG-confirmed diagnosis (26 min if the patient calls ambulance vs 52 min if they present at a general practitioner or outpatient clinic) and subsequent transportation to the cathlab (60 min for primary route, 97 for secondary). The latter two should be in particular targeted and we can see a significant room for improvement here.ConclusionThe time intervals do not vary among individual years (with some exceptions). The route of transportation, which is a patient's choice, on the total ischaemic time is however a crucial and predominant factor affecting the total ischaemic time as well as individual intervals.     

A Longitudinal Study of the Yield and Clinical Utility of a Specifically Designed Secondary Hypertension Investigation Protocol

Objective.?It has become common practice to use a day-case based approach to identify from the population of hypertensive patients those with an identifiable cause. We aimed to prospectively identify 96 consecutive hypertensive patients undergoing an algorithmic investigation protocol based around two day case hospital attendances. Methods.?The overall diagnostic yield and associated costs were recorded and the patients were observed for a mean of 2.5 years with ambulatory blood pressure (BP) monitoring every three months. Results.?A secondary cause of hypertension was identified in 18.1% of patients, three quarters of whom had renovascular disease. There was a fall in blood pressure with time (157/97 vs. 140/85) but this was associated with an increase in the amount of medication required (mean medication score 5.99 vs. 7.65). Improvement in BP occurred irrespective of whether or not a secondary cause was identified. Only 3.2% of patients were cured of their hypertension as a result of enrollment in the protocol. The cost of identifying each case of secondary hypertension was Euro 10, 196. Conclusions.?A comprehensive protocol aimed at identifying secondary hypertension had a low yield, the majority of whom had renovascular disease. In light of recent data illustrating the lack of improvement in BP following dilatation or bypass of atherosclerotic renovascular disease, it is debatable whether searching for it is justifiable.     

Parathyroid cancer: A systematic review of diagnostic biomarkers

IntroductionParathyroid cancers are rare and difficult to distinguish from benign parathyroid tumours. Prediction of malignancy often relies on intraoperative assessment of invasion. Standard histology is also inadequate; especially in the absence of local invasion, lymph nodal disease and metastasis. The aim of this project was to systematically review published literature on potential bio-markers used for the diagnosis of parathyroid cancer.MethodsPubmed, Web of Science and Medline databases were searched. Inclusion criteria included English language papers published after 1985 and reporting on biomarkers in human studies of parathyroid cancer and benign disease.Results118 relevant papers were appraised; all were observational studies. At least 2 papers studied 8 serum, 4 urine and 27 tissue biomarkers on the diagnosis of parathyroid cancer. Of these, 5 serum and 13 tissue markers have been demonstrated in at least one study to be statistically different in benign and malignant disease. We present a synthesis of data for each biomarker and measures of diagnostic accuracy where possible.ConclusionsConsideration should be given to the use of a panel of biomarkers to review patients with suspected parathyroid cancer. A profile including serum calcium and PTH levels and tissue expression of APC, Parafibromin, PGP9.5, Galectin 3 and Ki67 is proposed.Systematic Review Registration Number – CRD42019127833.