The role of preoperative aspartate aminotransferase-to-platelet ratio index in predicting complications following total hip arthroplasty.

BACKGROUND: The purpose of this study was to investigate the relationship between preoperative aspartate aminotransferase-to-platelet ratio index (APRI) and postoperative complications following total hip arthroplasty (THA). METHODS: All THA for osteoarthritis patients from 2007 to 2020 within the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database were included in this study. Subjects were subsequently divided into cohorts based on APRI. Four groups, including normal range, some liver damage, significant fibrosis, and cirrhosis groups, were created. Comparisons between groups were made for demographics, past medical history, and rate of major and minor complications. Other outcomes included readmission, reoperation, discharge destination, mortality, periprosthetic fracture, and postoperative hip dislocation. Multivariate logistic regression analysis was performed to determine the role of preoperative APRI in predicting adverse outcomes. Statistical significance was set at p < 0.05. RESULTS: In total, 104,633 primary THA patients were included in this study. Of these, 103,678 (99.1%) were in the normal APRI group, 444 (0.4%) had some liver damage, 256 (0.2%) had significant fibrosis, and 253 (0.2%) had cirrhosis. When controlling for demographics and relevant past medical history, the abnormal APRI groups had a significantly higher likelihood of major complication, minor complication, intraoperative or postoperative bleeding requiring transfusion, readmission, and non-home discharge (all p < 0.05) compared to normal APRI individuals. CONCLUSIONS: Abnormal preoperative APRI is linked with an increasing number of adverse outcomes following THA for osteoarthritis for patients across the United States. LEVEL OF EVIDENCE: Level I.

Clonal evolution revealed by whole genome sequencing in a case of primary myelofibrosis transformed to secondary acute myeloid leukemia.

Clonal architecture in myeloproliferative neoplasms (MPNs) is poorly understood. Here we report genomic analyses of a patient with primary myelofibrosis (PMF) transformed to secondary acute myeloid leukemia (sAML). Whole genome sequencing (WGS) was performed on PMF and sAML diagnosis samples, with skin included as a germline surrogate. Deep sequencing validation was performed on the WGS samples and an additional sample obtained during sAML remission/relapsed PMF. Clustering analysis of 649 validated somatic single-nucleotide variants revealed four distinct clonal groups, each including putative driver mutations. The first group (including JAK2 and U2AF1), representing the founding clone, included mutations with high frequency at all three disease stages. The second clonal group (including MYB) was present only in PMF, suggesting the presence of a clone that was dispensable for transformation. The third group (including ASXL1) contained mutations with low frequency in PMF and high frequency in subsequent samples, indicating evolution of the dominant clone with disease progression. The fourth clonal group (including IDH1 and RUNX1) was acquired at sAML transformation and was predominantly absent at sAML remission/relapsed PMF. Taken together, these findings illustrate the complex clonal dynamics associated with disease evolution in MPNs and sAML.

The management of acute seizures in Naval Service personnel.

Seizures are a relatively common Emergency Department (ED) presentation among young adult populations, considered for the purpose of this report as being aged 15-59. Due to the varied aetiologies involved, understanding of the potential causes and their presentation is key to managing these patients. Although seizure incidence within the United Kingdom (UK) Armed Forces population is generally low, it is not negligible. Therefore, awareness of the initial management is required by all those involved in patient care from the Medical Assistant (MA) at the Role 1 facility, through to the senior doctors at Role 3 establishments. All management should be in line with the Clinical Guidelines for Operations (CGOs) and Advanced Life Support (ALS) principles, with resuscitation, seizure control and patient stabilisation taking precedence initially. Ultimately, the use of laboratory testing and imaging at a Role 3 setting will be required to accurately confirm a diagnosis. Information obtained during these assessments may serve to assist the Naval Service Medical Board of Survey (NSMBOS) in determining suitability for continued Service retention and employment.

Clonal diversity of recurrently mutated genes in myelodysplastic syndromes.

Recent studies suggest that most cases of myelodysplastic syndrome (MDS) are clonally heterogeneous, with a founding clone and multiple subclones. It is not known whether specific gene mutations typically occur in founding clones or subclones. We screened a panel of 94 candidate genes in a cohort of 157 patients with MDS or secondary acute myeloid leukemia (sAML). This included 150 cases with samples obtained at MDS diagnosis and 15 cases with samples obtained at sAML transformation (8 were also analyzed at the MDS stage). We performed whole-genome sequencing (WGS) to define the clonal architecture in eight sAML genomes and identified the range of variant allele frequencies (VAFs) for founding clone mutations. At least one mutation or cytogenetic abnormality was detected in 83% of the 150 MDS patients and 17 genes were significantly mutated (false discovery rate ≤0.05). Individual genes and patient samples displayed a wide range of VAFs for recurrently mutated genes, indicating that no single gene is exclusively mutated in the founding clone. The VAFs of recurrently mutated genes did not fully recapitulate the clonal architecture defined by WGS, suggesting that comprehensive sequencing may be required to accurately assess the clonal status of recurrently mutated genes in MDS.

Recurrent DNMT3A mutations in patients with myelodysplastic syndromes.

Alterations in DNA methylation have been implicated in the pathogenesis of myelodysplastic syndromes (MDS), although the underlying mechanism remains largely unknown. Methylation of CpG dinucleotides is mediated by DNA methyltransferases, including DNMT1, DNMT3A and DNMT3B. DNMT3A mutations have recently been reported in patients with de novo acute myeloid leukemia (AML), providing a rationale for examining the status of DNMT3A in MDS samples. In this study, we report the frequency of DNMT3A mutations in patients with de novo MDS, and their association with secondary AML. We sequenced all coding exons of DNMT3A using DNA from bone marrow and paired normal cells from 150 patients with MDS and identified 13 heterozygous mutations with predicted translational consequences in 12/150 patients (8.0%). Amino acid R882, located in the methyltransferase domain of DNMT3A, was the most common mutation site, accounting for 4/13 mutations. DNMT3A mutations were expressed in the majority of cells in all tested mutant samples regardless of myeloblast counts, suggesting that DNMT3A mutations occur early in the course of MDS. Patients with DNMT3A mutations had worse overall survival compared with patients without DNMT3A mutations (P=0.005) and more rapid progression to AML (P=0.007), suggesting that DNMT3A mutation status may have prognostic value in de novo MDS.

Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.

BACKGROUND: The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high resolution genome analyses in patients with unexplained mental retardation. AIM: We report the molecular and/or clinical characterisation of 22 individuals with the 17q21.31 microdeletion syndrome. RESULTS: We estimate the prevalence of the syndrome to be 1 in 16,000 and show that it is highly underdiagnosed. Extensive clinical examination reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour are the most characteristic features. Other clinically important features include epilepsy, heart defects and kidney/urologic anomalies. Using high resolution oligonucleotide arrays we narrow the 17q21.31 critical region to a 424 kb genomic segment (chr17: 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the recurrent deletion, failed to identify any disease associated variants. In five deletion carriers we identify a <500 bp rearrangement hotspot at the proximal breakpoint contained within an L2 LINE motif and show that in every case examined the parent originating the deletion carries a common 900 kb 17q21.31 inversion polymorphism, indicating that this inversion is a necessary factor for deletion to occur (p<10(-5)). CONCLUSION: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.

In vivo multiphoton imaging of a transgenic mouse model of Alzheimer disease reveals marked thioflavine-S-associated alterations in neurite trajectories.

Postmortem analyses of senile plaques reveal numerous dystrophic processes in their vicinity. We used in vivo multiphoton microscopy of a transgenic model of Alzheimer disease (AD) to simultaneously image senile plaques and nearby neuronal processes. Plaques were labeled by immunofluorescent staining or thioflavine-S and neuronal processes were labeled with a fluorescent dextran conjugate. Imaging of 3-dimensional volumes in the vicinity of plaques revealed subtle changes in neurite geometry in or near diffuse plaques. By contrast, disruptions in neurite morphology, including dystrophic neurites immediately surrounding plaques as well as major alterations in neurite trajectories, were seen in association with thioflavine-S-positive plaques. Nearly half of all labeled processes that came within 50 microm of a thioflavine-S-positive plaque were altered, suggesting a fairly large "halo" of neuropil alterations that extend beyond the discrete border of a thioflavine-S plaque. These results support the hypothesis that compact thioflavine-S-positive plaques disrupt the neuropil in AD.

Estrogen and xenoestrogens upregulate the brain aromatase isoform (P450aromB) and perturb markers of early development in zebrafish (Danio rerio).

Estrogen synthesized in the brain itself by the action of cytochrome P450 aromatase (P450arom) is known to have permanent organizing effects on the developing CNS. In fish, estrogen upregulates the predominant brain isoform (P450aromB), implying that xenoestrogens (XE) could act as neurodevelopmental toxicants by altering P450aromB. To test this hypothesis, zebrafish embryos were exposed to 17beta-estradiol (E(2)), diethylstilbestrol (DES, a potent agonist), and bisphenol A (BPA, a weak agonist). RT-PCR/Southern transfer analysis showed that E(2) (0.01-10 microM) upregulated P450aromB in a dose-response manner. The effect of DES (0.01 microM) was similar to 1 microM E(2) (three- to four-fold higher than control), but BPA was less effective (

Universal newborn hearing screening.

BACKGROUND: New technology has made universal newborn hearing screening possible. Our goal was to investigate the feasibility of universal newborn screening using distortion product otoacoustic emissions (DPOAE) on infants in a community hospital in a normal newborn nursery. METHODS: We used DPOAE to screen newborn infants from February 1997 to March 1999. RESULTS: Of 1002 infants, 111 failed the initial screen (11.1%). When screening was repeated, only 2 infants failed. One infant failed the second screen and a tympanogram. He was treated and he passed a third use of DPOAE. An additional infant failed the repeat screen but passed the tympanogram. That infant was referred on for auditory brain response testing. CONCLUSIONS: DPOAE testing can be accomplished easily in a normal newborn nursery with an acceptable false-positive rate when a two-stage approach is used. The cost for each test was $19.88. The cost to find the 1 infant with sensory neural hearing loss was $22,114.

Effect of scavenging on the psychomotor and cognitive function of subjects sedated with nitrous oxide and oxygen inhalation.

Maximizing scavenger effectiveness using a 45 L/min evacuation rate as recommended by the National Institute of Occupational Safety and Health (NIOSH) may alter the sedation level of the dental patient. The purpose of this pilot study was to determine if scavenging at the recommended NIOSH evacuation rate reduced psychomotor and cognitive impairment as a result of inhaling nitrous oxide. Computer-administered neurobehavioral tests of human psychomotor and cognitive function previously established in controlled trials to be sensitive to nitrous oxide inhalation were employed in this blind, randomized, crossover study of 30 healthy adult subjects. The results indicated that scavenging produced statistically significant improvement in finger-tapping speed, symbol/digit coding speed, and recall accuracy. Hand/eye coordination was not improved significantly by scavenging. Enhancement of psychomotor skills and cognitive functioning was interpreted as an undesirable side effect of scavenging that could potentially influence dental patient anxiety management when using nitrous oxide inhalation. The results of this pilot study suggested that scavenger operation under the conditions tested could reduce the level of psychosedation achieved with nitrous oxide inhalation.

Heat resistance of Escherichia coli O157:H7 in apple juice.

The objective was to determine the effect of cider composition on the heat resistance of Escherichia coli O157:H7. The average D52 value in a model Empire apple juice was 18 min with a z value of 4.8 degrees C. Increasing the Brix from 11.8 to 16.5 degrees had no effect on thermal resistance, while increasing L-malic acid from 0.2 to 0.8%, or reducing the pH from 4.4 to 3.6 sensitized the cells to heat. The greatest effect on heat resistance was afforded by the preservatives benzoic and sorbic acids: D50 values in ciders containing 1,000 mg/l were 5.2 min in the presence of sorbic acid and only 0.64 min in the presence of benzoic acid. Commercial apple juice concentrates yielded lower numbers of survivors than single-strength juices even though their higher sugar concentrations of about 46 degrees Brix increased heat resistance.