The contemporary pulmonary artery catheter. Part 2:measurements, limitations, and clinical applications

Nowadays, the classical pulmonary artery catheter (PAC) has an almost 50-year-old history of its clinical use for hemodynamic monitoring. In recent years, the PAC evolved from a device that enabled intermittent cardiac output measurements in combination with static pressures to a monitoring tool that provides continuous data on cardiac output, oxygen supply and-demand balance, as well as right ventricular performance. In this review, which consists of two parts, we will introduce the difference between intermittent pulmonary artery thermodilution using bolus injections, and the contemporary PAC enabling continuous measurements by using a thermal filament which heats up the blood. In this second part, we will discuss in detail the measurements of the contemporary PAC, including continuous cardiac output measurement, right ventricular ejection fraction, end-diastolic volume index, and mixed venous oxygen saturation. Limitations of all of these measurements are highlighted as well. We conclude that thorough understanding of measurements obtained from the PAC is the first step in successful application of the PAC in daily clinical practice

The contemporary pulmonary artery catheter. Part 1:placement and waveform analysis

Nowadays, the classical pulmonary artery catheter (PAC) has an almost 50-year-old history of its clinical use for hemodynamic monitoring. In recent years, the PAC evolved from a device that enabled intermittent cardiac output measurements in combination with static pressures to a monitoring tool that provides continuous data on cardiac output, oxygen supply and-demand balance, as well as right ventricular (RV) performance. In this review, which consists of two parts, we will introduce the difference between intermittent pulmonary artery thermodilution using cold bolus injections, and the contemporary PAC enabling continuous measurements by using a thermal filament which at random heats up the blood. In this first part, the insertion techniques, interpretation of waveforms of the PAC, the interaction of waveforms with the respiratory cycle and airway pressure as well as pitfalls in waveform analysis are discussed. The second part will cover the measurements of the contemporary PAC including measurement of continuous cardiac output, RV ejection fraction, end-diastolic volume index, and mixed venous oxygen saturation. Limitations of all of these measurements will be highlighted there as well. We conclude that thorough understanding of measurements obtained from the PAC are the first step in successful application of the PAC in daily clinical practice

Examining the distribution and impact of single nucleotide polymorphisms in the capsular locus of Streptococcus pneumoniae serotype 19A

Streptococcus pneumoniae serotype 19A prevalence has increased after implementation of PCV7 and PCV10 vaccines. In this study, we have provided, with high accuracy, the genetic diversity of the 19A serotype in a cohort of Dutch invasive pneumococcal disease patients and asymptomatic carriers obtained in the period 2004-2016. Whole genomes of the 338 pneumococcal isolates in this cohort were sequenced and their capsule (cps) loci compared to examine the diversity and determine the impact on the production of CPS sugar precursors and CPS shedding. We discovered 79 types with a unique CPS locus sequence. Most variation was observed in the rmlB and rmlD genes of the TDP-Rha synthesis pathway, and in the wzg gene, of unknown function. Interestingly, gene variation in the cps locus was conserved in multiple alleles. Using RmlB and RmlD protein models, we predict that enzymatic function is not affected by the single nucleotide polymorphisms as identified. To determine if RmlB and RmlD function was affected, we analyzed nucleotide sugar levels using UHPLC-MS. CPS precursors differed between 19A cps locus subtypes, including TDP-Rha, but no clear correlation was observed. Also, a significant difference in multiple nucleotide sugar levels was observed between phylogenetically branched groups. Because of indications of a role for Wzg in capsule shedding, we analyzed if this was affected. No clear indication of a direct role in shedding was found. We thus describe genotypic variety in rmlB, rmlD and wzg in serotype 19A the Netherlands, for which we have not discovered an associated phenotype

Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates

Contains fulltext : 97744.pdf (publisher's version ) (Open Access)BACKGROUND: M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed. RESULTS: The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement. CONCLUSIONS: M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens

Systemic phenotype related to primary Sjögren's syndrome in 279 patients carrying isolated anti-La/SSB antibodies

Objective. To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria. Methods. The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immu-nological phenotypes: Double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/ SSB, and immunonegative. Results. The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥ 1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/ SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in com-parison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/ SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group. Conclusion. Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients

Adaptive Stress Response in Segmental Progeria Resembles Long-Lived Dwarfism and Calorie Restriction in Mice

How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age), including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPD(G602D/R722W)/XPA(−/−)) that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80 (−/−) mouse. Specific (but not all) types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage

Age-Related Skeletal Dynamics and Decrease in Bone Strength in DNA Repair Deficient Male Trichothiodystrophy Mice

Accumulation of DNA damage caused by oxidative stress is thought to be one of the main contributors of human tissue aging. Trichothiodystrophy (TTD) mice have a mutation in the Ercc2 DNA repair gene, resulting in accumulation of DNA damage and several features of segmental accelerated aging. We used male TTD mice to study the impact of DNA repair on bone metabolism with age. Analysis of bone parameters, measured by micro-computed tomography, displayed an earlier decrease in trabecular and cortical bone as well as a loss of periosteal apposition and a reduction in bone strength in TTD mice with age compared to wild type mice. Ex vivo analysis of bone marrow differentiation potential showed an accelerated reduction in the number of osteogenic and osteoprogenitor cells with unaltered differentiation capacity. Adipocyte differentiation was normal. Early in life, osteoclast number tended to be increased while at 78 weeks it was significantly lower in TTD mice. Our findings reveal the importance of genome stability and proper DNA repair for skeletal homeostasis with age and support the idea that accumulation of damage interferes with normal skeletal maintenance, causing reduction in the number of osteoblast precursors that are required for normal bone remodeling leading to a loss of bone structure and strength

Association between the metabolic syndrome and its components and gait speed among U.S. adults aged 50 years and older: a cross-sectional analysis

BACKGROUND: To examine the relationship between the metabolic syndrome and its components and gait speed among older U.S. men and women. Whether these associations are independent of physical activity was also explored. METHODS: Eight hundred and thirty-five men and 850 women aged ≥50 years from the continuous National Health and Nutrition Examination Survey 1999–2002 were examined. We used the definition of the metabolic syndrome developed by the U.S. National Cholesterol Education Program Adult Treatment Panel III. Gait speed was measured with a 6.10-meter timed walk examination. RESULTS: The prevalence of the metabolic syndrome was 40.2% in men and 45.6% in women (P = .127). The prevalence of gait speed impairment was 29.3% in men and 12.5% in women (P < .001). No association was found between the metabolic syndrome and gait speed impairment. After including the individual components of the metabolic syndrome in a logistic model adjusted for age and leisure-time physical activity, abdominal obesity, low HDL cholesterol, and high fasting glucose were significantly associated with gait speed impairment among women (adjusted odds ratio [AOR] = 0.48, 95% confidence interval [CI] = 0.26 to 0.89; AOR = 2.26, 95% CI = 1.08 to 4.75; and AOR = 2.05, 95% CI = 1.12 to 3.74, respectively). Further adjustment for race/ethnicity, education, smoking status, alcohol consumption, arthritis status, and use of an assistive device attenuated these associations; among women, abdominal obesity and low HDL cholesterol remained significantly associated with gait speed impairment (AOR = 0.37, 95% CI = 0.18 to 0.76 and AOR = 2.45, 95% CI = 1.07 to 5.63, respectively) while the association between hyperglycemia and impaired gait speed attenuated to nonsignificance. CONCLUSION: Among women, gait speed impairment is associated with low HDL cholesterol and inversely with abdominal obesity. These associations may be sex-dependent and warrant further research