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BACKGROUND: Lipid profiling is central for coronary artery disease (CAD) risk assessment. Nonadherence or unreported use of lipid-lowering drugs, particularly statins, can significantly complicate the association between lipid profile measures and CAD clinical outcomes. By combining medication history evaluation with statin analysis in plasma, we determined the effects of inaccurately reported statin use on lipid profile measures and their association with CAD risk. METHODS: We compared medication history of statin use with statin concentration measurements, by liquid chromatography-tandem mass spectrometry, in 690 participants undergoing coronary angiography (63 ± 11 years of age). Nominal logistic regression was employed to model CAD diagnosis with statin measurements, phenotypic, and lipid profile characteristics. RESULTS: Medication history of statin use was confirmed by statin assay for 81% of the patients. Surprisingly, statins were detected in 46% of patients without statin use records. Nonreported statin use was disproportionately higher among older participants. Stratifying samples by statin history resulted in underestimated LDL-lipid measures. Apolipoprotein B concentrations had a significant inverse CAD association, which became nonsignificant upon re-stratification using the statin assay data. CONCLUSIONS: Our study uncovered prominent discrepancies between medication records and actual statin use measured by mass spectrometry. We showed that inaccurate statin use assessments may lead to overestimation and underestimation of LDL levels in statin user and nonuser categories, exaggerating the reverse epidemiology association between LDL levels and CAD diagnosis. Combining medication history and quantitative statin assay data can significantly improve the design, analysis, and interpretation of clinical and epidemiological studies.
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Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos , Medição de Risco , Fatores de Risco , Pessoa de Meia-Idade , IdosoRESUMO
RATIONALE & OBJECTIVE: A history of prior abdominal procedures may influence the likelihood of referral for peritoneal dialysis (PD) catheter insertion. To guide clinical decision making in this population, this study examined the association between prior abdominal procedures and outcomes in patients undergoing PD catheter insertion. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults undergoing their first PD catheter insertion between November 1, 2011, and November 1, 2020, at 11 institutions in Canada and the United States participating in the International Society for Peritoneal Dialysis North American Catheter Registry. EXPOSURE: Prior abdominal procedure(s) defined as any procedure that enters the peritoneal cavity. OUTCOMES: The primary outcome was time to the first of (1) abandonment of the PD catheter or (2) interruption/termination of PD. Secondary outcomes were rates of emergency room visits, hospitalizations, and procedures. ANALYTICAL APPROACH: Cumulative incidence curves were used to describe the risk over time, and an adjusted Cox proportional hazards model was used to estimate the association between the exposure and primary outcome. Models for count data were used to estimate the associations between the exposure and secondary outcomes. RESULTS: Of 855 patients who met the inclusion criteria, 31% had a history of a prior abdominal procedure and 20% experienced at least 1 PD catheter-related complication that led to the primary outcome. Prior abdominal procedures were not associated with an increased risk of the primary outcome (adjusted HR, 1.12; 95% CI, 0.68-1.84). Upper-abdominal procedures were associated with a higher adjusted hazard of the primary outcome, but there was no dose-response relationship concerning the number of procedures. There was no association between prior abdominal procedures and other secondary outcomes. LIMITATIONS: Observational study and cohort limited to a sample of patients believed to be potential candidates for PD catheter insertion. CONCLUSION: A history of prior abdominal procedure(s) does not appear to influence catheter outcomes following PD catheter insertion. Such a history should not be a contraindication to PD. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is a life-saving therapy for individuals with kidney failure that can be done at home. PD requires the placement of a tube, or catheter, into the abdomen to allow the exchange of dialysis fluid during treatment. There is concern that individuals who have undergone prior abdominal procedures and are referred for a catheter might have scarring that could affect catheter function. In some institutions, they might not even be offered PD therapy as an option. In this study, we found that a history of prior abdominal procedures did not increase the risk of PD catheter complications and should not dissuade patients from choosing PD or providers from recommending it.
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Cateteres de Demora , Diálise Peritoneal , Sistema de Registros , Humanos , Masculino , Feminino , Diálise Peritoneal/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Cateteres de Demora/efeitos adversos , Falência Renal Crônica/terapia , Falência Renal Crônica/epidemiologia , Canadá/epidemiologia , Idoso , Estados Unidos/epidemiologia , Abdome/cirurgia , Adulto , Cateterismo/métodos , Cateterismo/efeitos adversosRESUMO
BACKGROUND: This study investigated the association of intra-abdominal adhesions with the risk of peritoneal dialysis (PD) catheter complications. METHODS: Individuals undergoing laparoscopic PD catheter insertion were prospectively enrolled from eight centers in Canada and the United States. Patients were grouped based on the presence of adhesions observed during catheter insertion. The primary outcome was the composite of PD never starting, termination of PD, or the need for an invasive procedure caused by flow restriction or abdominal pain. RESULTS: Seven hundred and fifty-eight individuals were enrolled, of whom 201 (27%) had adhesions during laparoscopic PD catheter insertion. The risk of the primary outcome occurred in 35 (17%) in the adhesion group compared with 58 (10%) in the no adhesion group (adjusted HR, 1.64; 95% confidence interval [CI], 1.05 to 2.55) within 6 months of insertion. Lower abdominal or pelvic adhesions had an adjusted HR of 1.80 (95% CI, 1.09 to 2.98) compared with the no adhesion group. Invasive procedures were required in 26 (13%) and 47 (8%) of the adhesion and no adhesion groups, respectively (unadjusted HR, 1.60: 95% CI, 1.04 to 2.47) within 6 months of insertion. The adjusted odds ratio for adhesions for women was 1.65 (95% CI, 1.12 to 2.41), for body mass index per 5 kg/m 2 was 1.16 (95% CI, 1.003 to 1.34), and for prior abdominal surgery was 8.34 (95% CI, 5.5 to 12.34). Common abnormalities found during invasive procedures included PD catheter tip migration, occlusion of the lumen with fibrin, omental wrapping, adherence to the bowel, and the development of new adhesions. CONCLUSIONS: People with intra-abdominal adhesions undergoing PD catheter insertion were at higher risk for abdominal pain or flow restriction preventing PD from starting, PD termination, or requiring an invasive procedure. However, most patients, with or without adhesions, did not experience complications, and most complications did not lead to the termination of PD therapy.
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Laparoscopia , Diálise Peritoneal , Humanos , Feminino , Cateteres de Demora/efeitos adversos , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Cateterismo , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Dor Abdominal , Estudos RetrospectivosRESUMO
Background and Objectives: Caregiving is a social process and commonly involves more than a single caregiver, especially for older adults with multimorbidity, including dementia. This study was to characterize informal caregiving networks of older adults with dementia superimposed on multimorbidity (e.g., end-stage kidney disease) and to examine the relationships of network properties to outcomes of caregivers and older adults. Research Design and Methods: An egocentric social network survey was conducted. Up to 3 family caregivers of older adults on dialysis who had moderate-to-severe irreversible cognitive impairment with or without a documented diagnosis of dementia were recruited from 11 dialysis centers in 2 states. Caregivers completed a social network survey about individuals providing caregiving to the older adult and measures of caregiving burden and rewards, depression, and financial hardship. Older adults' emergency department visits and hospital admissions during the past 12 months were abstracted from the medical records. Results: A total of 76 caregiver informants of 46 older adults (78% Black) participated in the study. Of the 46 older adults, 65% had a multimember network (median size of 4). As the network density (the proportion of ties between members among all possible ties) increased, primary caregivers' financial hardship decreased whereas nonprimary caregivers' financial hardship increased. Further, for every 1-unit increase in mean degree (the average number of connections among members), there was a nearly fourfold increase in the odds of no hospital admission during the prior year for the older adult. Discussion and Implications: The network dynamics of informal caregiving networks may have an impact on the well-being of caregivers and older adults with dementia, but confirmatory longitudinal studies are needed.
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Designing studies for lipid-metabolism-related biomarker discovery is challenging because of the high prevalence of various statin and fibrate usage for lipid-lowering therapies. When the statin and fibrate use is determined based on self-reports, patient adherence to the prescribed statin dose regimen remains unknown. A potentially more accurate way to verify a patient's medication adherence is by direct analytical measurements. Current analytical methods are prohibitive because of the limited panel of drugs per test and large sample volume requirement that is not available from archived samples. A 4-min-long method was developed for the detection of seven statins and three fibrates using 10 µL of plasma analyzed via reverse-phase liquid chromatography and tandem mass spectrometry. The method was applied to the analysis of 941 archived plasma samples collected from patients before cardiac catheterization. When statin use was self-reported, statins were detected in 78.6% of the samples. In the case of self-reported atorvastatin use, the agreement with detection was 90.2%. However, when no statin use was reported, 42.4% of the samples had detectable levels of statins, with a similar range of concentrations as the samples from the self-reported statin users. The method is highly applicable in population studies designed for biomarker discovery or diet and lifestyle intervention studies, where the accuracy of statin or fibrate use may strongly affect the statistical evaluation of the biomarker data.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ácidos Fíbricos/uso terapêutico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Atorvastatina/uso terapêutico , BiomarcadoresRESUMO
Inhalation anthrax has three clinical stages: early-prodromal, intermediate-progressive, and late-fulminant. We report the comprehensive characterization of anthrax toxins, including total protective antigen (PA), total lethal factor (LF), total edema factor (EF), and their toxin complexes, lethal toxin and edema toxin in plasma, during the course of inhalation anthrax in 23 cynomolgus macaques. The toxin kinetics were predominantly triphasic with an early rise (phase-1), a plateau/decline (phase-2), and a final rapid rise (phase-3). Eleven animals had shorter survival times, mean±standard deviation of 58.7±7.6 hours (fast progression), 11 animals had longer survival times, 113±34.4 hours (slow progression), and one animal survived. Median (lower-upper quartile) LF levels at the end-of-phase-1 were significantly higher in animals with fast progression [138 (54.9-326) ng/mL], than in those with slow progression [23.8 (15.6-26.3) ng/mL] (p = 0.0002), and the survivor (11.1 ng/mL). The differences were also observed for other toxins and bacteremia. Animals with slow progression had an extended phase-2 plateau, with low variability of LF levels across all time points and animals. Characterization of phase-2 toxin levels defined upper thresholds; critical levels for exiting phase-2 and entering the critical phase-3, 342 ng/mL (PA), 35.8 ng/mL (LF), and 1.10 ng/mL (EF). The thresholds were exceeded earlier in animals with fast progression (38.5±7.4 hours) and later in animals with slow progression (78.7±15.2 hours). Once the threshold was passed, toxin levels rose rapidly in both groups to the terminal stage. The time from threshold to terminal was rapid and similar; 20.8±7.4 hours for fast and 19.9±7.5 hours for slow progression. The three toxemic phases were aligned with the three clinical stages of anthrax for fast and slow progression which showed that anthrax progression is toxin- rather than time-dependent. This first comprehensive evaluation of anthrax toxins provides new insights into disease progression.
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Antraz , Bacillus anthracis , Infecções Respiratórias , Animais , Antígenos de Bactérias , Macaca mulattaRESUMO
Aberrations in lipid and lipoprotein metabolic pathways can lead to numerous diseases, including cardiovascular disease, diabetes, neurological disorders, and cancer. The integration of quantitative lipid and lipoprotein profiling of human plasma may provide a powerful approach to inform early disease diagnosis and prevention. In this study, we leveraged data-driven quantitative targeted lipidomics and proteomics to identify specific molecular changes associated with different metabolic risk categories, including hyperlipidemic, hypercholesterolemic, hypertriglyceridemic, hyperglycemic, and normolipidemic conditions. Based on the quantitative characterization of serum samples from 146 individuals, we have determined individual lipid species and proteins that were significantly up- or down-regulated relative to the normolipidemic group. Then, we established protein-lipid topological networks for each metabolic category and linked dysregulated proteins and lipids with defined metabolic pathways. To evaluate the differentiating power of integrated lipidomics and proteomics data, we have built an artificial neural network model that simultaneously and accurately categorized the samples from each metabolic risk category based on the determined lipidomics and proteomics profiles. Together, our findings provide new insights into molecular changes associated with metabolic risk conditions, suggest new condition-specific associations between apolipoproteins and lipids, and may inform new biomarker discovery in lipid metabolism-associated disorders.
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Transtornos do Metabolismo dos Lipídeos , Lipidômica , Humanos , Proteômica , Metabolismo dos Lipídeos , Lipídeos , Biomarcadores/metabolismoRESUMO
The objective of this study was to examine long-term trends in serum cotinine (COT) concentrations, as a measure of secondhand smoke (SHS) exposure, in U.S. nonsmokers using data from the National Health and Nutrition Examination Surveys (NHANES) from 2003 to 2018. We analyzed NHANES serum COT results from 8 continuous NHANES 2 year cycles from 2003 to 2018 using a liquid chromatography−tandem mass spectrometry assay that has been maintained continuously at the Centers for Disease Control and Prevention (CDC) since 1992. Serum COT concentrations (based on the geometric means) among nonsmokers in the U.S. decreased by an average of 11.0% (95% confidence interval (CI) [8.8%, 13.1%]; p < 0.0001) every 2 year cycle. From 2003 to 2018, serum COT concentrations in U.S. nonsmokers declined by 55.0%, from 0.065 ng/mL in 2003−2004 to 0.029 ng/mL in 2017−2018 (p < 0.0001). Significant decreases in serum COT concentrations were observed in all demographic groups. While disparities between these groups seems to be shrinking over time, several previously observed disparities in SHS exposure remain in 2017−2018. Serum COT concentrations of the non-Hispanic Black population remained higher than those of non-Hispanic Whites and Mexican Americans (p < 0.0001). Additionally, serum COT concentrations were significantly higher for children aged 3−5 years than other age groups (p ≤ 0.0002), and men continued to have significantly higher serum COT concentrations than women (p = 0.0384). While there is no safe level of exposure to SHS, the decrease in serum COT concentrations in the U.S. population as well as across demographic groupings represents a positive public health outcome and supports the importance of comprehensive smoke-free laws and policies for workplaces, public places, homes, and vehicles to protect nonsmokers from SHS exposure.
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Cotinina , Poluição por Fumaça de Tabaco , Criança , Exposição Ambiental , Feminino , Humanos , Masculino , não Fumantes , Inquéritos NutricionaisRESUMO
INTRODUCTION: The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative cohort of tobacco product users and nonusers. The study's main purpose is to obtain longitudinal epidemiologic data on tobacco use and exposure among the US population. AIMS AND METHODS: Nicotine biomarkers-cotinine (COT) and trans-3'-hydroxycotinine (HCT)-were measured in blood samples collected from adult daily tobacco users and nonusers during Wave 1 of the PATH Study (2013-2014; n = 5012; one sample per participant). Participants' tobacco product use and exposure to secondhand smoke were categorized based on questionnaire responses. Nonusers were subdivided into never users and recent former users. Daily tobacco users were classified into seven tobacco product use categories: exclusive users of cigarette, smokeless tobacco, electronic cigarette, cigar, pipe, and hookah, as well as polyusers. We calculated sample-weighted geometric mean (GM) concentrations of cotinine, HCT, and the nicotine metabolite ratio (NMR) and evaluated their associations with tobacco use with adjustment for potential confounders. RESULTS: The GMs (95% confidence intervals) of COT and HCT concentrations for daily tobacco users were 196 (184 to 208) and 72.5 (67.8 to 77.4) ng/mL, and for nonusers they were 0.033 (0.028 to 0.037) and 0.021 (0.018 to 0.023) ng/mL. Exclusive smokeless tobacco users had the highest COT concentrations of all user groups examined. The GM NMR in daily users was 0.339 (95% confidence interval: 0.330 to 0.350). CONCLUSIONS: These nationally representative estimates of serum nicotine biomarkers could be the basis for reference ranges characterizing nicotine exposure for daily tobacco users and nonusers in the US adult population. IMPLICATIONS: This report summarizes the serum nicotine biomarker measurements in Wave 1 of the PATH Study. We are reporting the first estimates of HCT in serum for daily tobacco users and nonusers in the noninstitutionalized, civilian US adult population; the first nationally representative serum COT estimates for daily exclusive users of different tobacco products and daily polyusers; and the first nationally representative estimate of the serum NMR in daily tobacco users by age, race/ethnicity, and sex.
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Sistemas Eletrônicos de Liberação de Nicotina , Tabagismo , Adulto , Biomarcadores , Cotinina/análogos & derivados , Humanos , Nicotina , Nicotiana , Tabagismo/epidemiologiaRESUMO
Large epidemiological studies often require sample transportation and storage, presenting unique considerations when applying advanced lipidomics techniques. The goal of this study was to acquire lipidomics data on plasma and serum samples stored at potential preanalytical conditions (e.g., thawing, extracting, evaporating), systematically monitoring lipid species for a period of one month. Split aliquots of 10 plasma samples and 10 serum samples from healthy individuals were kept in three temperature-related environments: refrigerator, laboratory benchtop, or heated incubator. Samples were analyzed at six different time points over 28 days using a Bligh & Dyer lipid extraction protocol followed by direct infusion into a lipidomics platform using differential mobility with tandem mass spectrometry. The observed concentration changes over time were evaluated relative to method and inter-individual biological variability. In addition, to evaluate the effect of lipase enzyme levels on concentration changes during storage, we compared corresponding fasting and post-prandial plasma samples collected from 5 individuals. Based on our data, a series of low abundance free fatty acid (FFA), diacylglycerol (DAG), and cholesteryl ester (CE) species were identified as potential analytical markers for degradation. These FFA and DAG species are typically produced by endogenous lipases from numerous triacylglycerols (TAGs), and certain high abundance phosphatidylcholines (PCs). The low concentration CEs, which appeared to increase several fold, were likely mass-isobars from oxidation of other high concentration CEs. Although the concentration changes of the high abundant TAG, PC, and CE precursors remained within method variability, the concentration trends of FFA, DAG, and oxidized CE products should be systematically monitored over time to inform analysts about possible pre-analytical biases due to degradation in the study sample sets.
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N-glycosylation plays an important role in the structure and function of membrane and secreted proteins. The spike protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is heavily glycosylated and the major target for developing vaccines, therapeutic drugs and diagnostic tests. The first major SARS-CoV-2 variant carries a D614G substitution in the spike (S-D614G) that has been associated with altered conformation, enhanced ACE2 binding, and increased infectivity and transmission. In this report, we used mass spectrometry techniques to characterize and compare the N-glycosylation of the wild type (S-614D) or variant (S-614G) SARS-CoV-2 spike glycoproteins prepared under identical conditions. The data showed that half of the N-glycosylation sequons changed their distribution of glycans in the S-614G variant. The S-614G variant showed a decrease in the relative abundance of complex-type glycans (up to 45%) and an increase in oligomannose glycans (up to 33%) on all altered sequons. These changes led to a reduction in the overall complexity of the total N-glycosylation profile. All the glycosylation sites with altered patterns were in the spike head while the glycosylation of three sites in the stalk remained unchanged between S-614G and S-614D proteins.
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Glicopeptídeos/análise , Espectrometria de Massas/métodos , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/patologia , COVID-19/virologia , Cromatografia Líquida de Alta Pressão , Glicosilação , Humanos , Mutação , Ligação Proteica , Estrutura Terciária de Proteína , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/químicaRESUMO
Extrusion of the superficial cuff of a peritoneal dialysis (PD) catheter is an uncommon complication that may be associated with infection or malfunction. However, extrusion of both the superficial and deep cuffs of a double-cuff catheter is rare and uniformly associated with failure and peritonitis. We report a case of a presternal-type PD double-cuff catheter with extrusion of both cuffs through an abdominal exit site after 6 years of use that has remained functional, which has not been previously reported. In this case, the patient had achieved a 60-kg weight loss resulting in retraction of the subcutaneous tissue around both cuffs, while the catheter was held in place by the titanium connector between the presternal extension tubing and the inner, coiled catheter. In such special circumstances, extrusion of both cuffs may not necessitate urgent catheter removal. A review of the literature revealed previous cases of superficial cuff extrusions with catheters remaining functional but not with deep cuff extrusion.
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Understanding and applying pathophysiological concepts to patient care is an important skill for physicians in the clinical setting. Here, we present a case that demonstrates how the application of common physiological concepts relating to the widely accepted hyponatremia algorithm led to an accurate diagnosis of hyponatremia. This case documents iso-osmolar hyponatremia caused by orally administered polyethylene glycol absorption in the gastrointestinal tract. Herein, we discuss the workup and differential diagnosis for iso-osmolar hyponatremia in juxtaposition with the pathophysiological mechanisms unique to this case. We discuss these pathophysiological mechanisms based on the patients' laboratory data and responses to therapeutic interventions.
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A critical step in Raman spectroscopy is baseline correction. This procedure eliminates the background signals generated by residual Rayleigh scattering or fluorescence. Baseline correction procedures relying on asymmetric loss functions have been employed recently. They operate with a reduced penalty on positive spectral deviations that essentially push down the baseline estimates from invading Raman peak areas. However, their coupling with polynomial fitting may not be suitable over the whole spectral domain and can yield inconsistent baselines. Their requirement of the specification of a threshold and the non-convexity of the corresponding objective function further complicates the computation. Learning from their pros and cons, we have developed a novel baseline correction procedure called the iterative smoothing-splines with root error adjustment (ISREA) that has three distinct advantages. First, ISREA uses smoothing splines to estimate the baseline that are more flexible than polynomials and capable of capturing complicated trends over the whole spectral domain. Second, ISREA mimics the asymmetric square root loss and removes the need of a threshold. Finally, ISREA avoids the direct optimization of a non-convex loss function by iteratively updating prediction errors and refitting baselines. Through our extensive numerical experiments on a wide variety of spectra including simulated spectra, mineral spectra, and dialysate spectra, we show that ISREA is simple, fast, and can yield consistent and accurate baselines that preserve all the meaningful Raman peaks.
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Diabetes Mellitus Tipo 2/terapia , Deficiência de Magnésio/urina , Magnésio/urina , Idoso , Análise Química do Sangue , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Diagnóstico Diferencial , Feminino , Hemoglobinas Glicadas/análise , Glicosúria/complicações , Humanos , Hipotireoidismo/complicações , Deficiência de Magnésio/diagnóstico , Deficiência de Magnésio/etiologia , Poliúria/etiologia , Erros Inatos do Transporte Tubular Renal/diagnóstico , UrináliseRESUMO
Pauci-immune necrotizing and crescentic glomerulonephritis (GN) is the most common etiology of rapidly progressive GN. Clinical presentation in those afflicted is usually related to rapid loss of kidney function. We report the case of a 70-year-old woman who came to medical attention for signs and symptoms related to lower-extremity deep vein thrombosis (DVT). At presentation, the patient had biochemical abnormalities consistent with active GN, which quickly progressed to rapid loss in kidney function requiring renal replacement therapy. Kidney biopsy revealed small-vessel vasculitis with glomerular crescents. Serologic studies were negative for antineutrophil cytoplasmic antibody antibodies and other causes of acute GN. Plasmapheresis, immunosuppressive, and anticoagulant therapies were prescribed. Absence of other apparent end-organ involvement with vasculitis pointed toward renal-limited small-vessel vasculitis, yet presence of unprovoked DVT argues for systemic vascular inflammation. This case illustrates that venous thrombosis can be the presenting manifestation in patients with vasculitis and silent, severe end-organ involvement. The epidemiology and pathophysiology of venous thromboembolism in small-vessel vasculitis are discussed in this report.
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BACKGROUND: Irradiative sterilization of clinical specimens prior to chemical laboratory testing provides a way to not only sterilize pathogens and ensure laboratorian safety but also preserve sample volume and maintain compatibility with quantitative chemical diagnostic protocols. Since the compatibility of clinical biomarkers with gamma irradiation is not well characterized, a subset of diagnostic biomarkers ranging in molecular size, concentration, and clinical matrix was analyzed to determine recovery following gamma irradiation. METHODS: Sample irradiation of previously characterized quality control materials (QCs) at 5 Mrad was carried out at the Gamma Cell Irradiation Facility at the Centers for Disease Control and Prevention (CDC) in Atlanta, GA. Following irradiation, the QCs were analyzed alongside non-irradiated QCs to determine analyte recovery between dosed and control samples. RESULTS: Biomarkers for exposure to abrin, ricin, and organophosphorus nerve agents (OPNAs) were analyzed for their stability following gamma irradiation. The diagnostic biomarkers included adducts to butyrylcholinesterase, abrine, and ricinine, respectively, and were recovered at over 90% of their initial concentration. CONCLUSIONS: The results from this pilot study support the implementation of an irradiative sterilization protocol for possible mixed-exposure samples containing both chemical and biological threat agents (mixed CBTs). Furthermore, irradiative sterilization significantly reduces a laboratorian's risk of infection from exposure to an infectious agent without compromising chemical diagnostic testing integrity, particularly for diagnostic assays in which the chemical analyte has been shown to be fully conserved following a 5 Mrad irradiative dose.
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Biomarcadores , Raios gama , Esterilização , Alcaloides/análise , Alcaloides/química , Biomarcadores Farmacológicos/análise , Biomarcadores Farmacológicos/química , Segurança Química , Cromatografia Líquida de Alta Pressão , Qualidade de Produtos para o Consumidor , Segurança de Equipamentos , Alcaloides Indólicos/análise , Alcaloides Indólicos/química , Projetos Piloto , Piridonas/análise , Piridonas/química , Controle de Qualidade , Doses de Radiação , Esterilização/métodosRESUMO
BACKGROUND: A mandated reduction in the nicotine content of cigarettes could reduce smoking rate and prevalence. However, one concern is that smokers may compensate by increasing the intensity with which they smoke each cigarette to obtain more nicotine. This study assessed whether smokers engage in compensatory smoking by estimating the mouth-level nicotine intake of low nicotine cigarettes smoked during a clinical trial. METHODS: Smokers were randomly assigned to receive cigarettes with one of five nicotine contents for 6 weeks. An additional group received a cigarette with the lowest nicotine content, but an increased tar yield. The obtained mouth-level nicotine intake from discarded cigarette butts for a subset of participants (51-70/group) was estimated using solanesol as described previously. A compensation index was calculated for each group to estimate the proportion of nicotine per cigarette recovered through changes in smoking intensity. RESULTS: There was no significant increase in smoking intensity for any of the reduced nicotine cigarettes as measured by the compensation index (an estimated 0.4% of the nicotine lost was recovered in the lowest nicotine group; 95% confidence interval, -0.1 to 1.2). There was a significant decrease in smoking intensity for very low nicotine content cigarettes with increased tar yield. CONCLUSIONS: Reductions in nicotine content did not result in compensatory changes in how intensively participants smoked research cigarettes. IMPACT: Combined with data from clinical trials showing a reduction in cigarettes smoked per day, these data suggest that a reduction in nicotine content is unlikely to result in increased smoke exposure.
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Fumar Cigarros/terapia , Nicotina/análise , Redução do Consumo de Tabaco/métodos , Produtos do Tabaco/normas , Adulto , Fumar Cigarros/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca , Nicotina/efeitos adversos , Nicotina/normas , Fumantes/estatística & dados numéricos , Terpenos/análise , Produtos do Tabaco/efeitos adversosRESUMO
BACKGROUND: Peritoneal dialysis (PD) is a more cost-effective therapy to treat kidney failure than in-center hemodialysis, but successful therapy requires a functioning PD catheter that causes minimal complications. In 2015, the North American Chapter of the International Society for Peritoneal Dialysis established the North American PD Catheter Registry to improve practices and patient outcomes following PD catheter insertion. AIMS: The objective of this study is to propose a methodology for defining insertion-related complications that lead to significant adverse events and report the risk of these complications among patients undergoing laparoscopic PD catheter insertion. METHODS: Patients undergoing laparoscopic PD catheter insertion were enrolled at 14 participating centers in Canada and the United States and followed using a Web-based registry. Insertion-related complications were defined as flow restriction, exit-site leak, or abdominal pain at any point during follow-up. We also included infections or bleeding within 30 days of insertion, and any immediate postoperative complications. Adverse events were categorized as PD never starting or termination of PD therapy, delay in the start of PD therapy or interruption of PD therapy, an emergency department visit or hospitalization, or need for invasive procedures. Cause-specific cumulative incidence functions were used to estimate risk. RESULTS: Five hundred patients underwent laparoscopic PD catheter insertion between 10 November 2015 and 24 July 2018. The cumulative risk of insertion-related complications 6 months from the date of insertion that led to an adverse event was 24%. The risk of flow restriction, exit-site leak, and pain at 6 months was 10.2%, 5.7%, and 5.3%, respectively. PD was never started or terminated in 6.4% of patients due to an insertion-related complication. Leaks and flow restrictions were most likely to delay or interrupt PD therapy. Flow restrictions were the primary cause of invasive procedures. Fifty percent of the complications occurred before the start of PD therapy. CONCLUSIONS: Insertion-related complications leading to significant adverse events following laparoscopic placement of PD catheters are common. Many complications occur before the start of PD. Insertion-related complications are an important area of focus for future research and quality improvement efforts.