Restoration of the native humeral anatomy during stemless anatomic total shoulder arthroplasty: a radiographic comparison of intramedullary versus freehand resection.

BACKGROUND: During anatomic total shoulder arthroplasty (aTSA), the humeral head can be resected with or without the use of an intramedullary cutting guide, the former referred to as intramedullary (IM) resection and the latter referred to as freehand (FH) resection. Outcomes following aTSA are predicated upon the restoration of the native humeral anatomy, which can be more challenging with stemless implants. To date, no studies have determined which method of humeral head resection is superior in restoring native anatomy. Our purpose was to determine whether FH or IM resection was superior in restoring native anatomy during aTSA with stemless implants. METHODS: A review of all patients who underwent aTSA using the stemless Tornier Simpliciti Shoulder System at two academic institutions by two separate surgeons between January 2017 and June 2020 was performed. One surgeon at one institution performed stemless aTSA using the IM resection technique, while the second surgeon utilized the FH resection technique. Patients were excluded if they underwent surgery for an indication other than glenohumeral osteoarthritis, if they received a short-stem or standard-stem implant, or if they lacked adequate preoperative and postoperative Grashey radiographs. One hundred eleven patients across both institutions (51 IM, 60 FH) were included for the final radiographic assessment. The humeral head height (HH) and neck-shaft angle (NSA) were measured on preoperative and postoperative Grashey radiographs. The centers of rotation (CORs) were measured on postoperative Grashey radiographs. Patients were classified as having acceptable restoration of their native anatomy if the change (Δ) in COR or HH was ≤3 mm and ≤ 5 mm, respectively, or if the postoperative NSA was ≥130°. RESULTS: IM resection had the greatest acceptable restoration of COR (90.2% IM versus 70% FH, P = .009), HH (96.1% IM vs. 63.3% FH, P < .001), and NSA (96.1% IM vs. 78.3% FH, P = .006) relative to FH resection. The mean postoperative NSAs for the IM and FH cohorts were 134.4° (±2.1°) and 133.8° (±5.4°), respectively (P = .208). The mean ΔCORs for the IM and FH groups were 1.2 (±1.5) and 2.3 (±1.2) mm, respectively (P < .001). Finally, the mean ΔHHs for the IM and FH cohorts were 1.7 (±1.4) and 4.4 (±2.9) mm, respectively (P < .001). CONCLUSIONS: Restoration of the native humeral anatomy following stemless aTSA occurred at a significantly higher rate when using IM vs. FH resection.

DRPPM-EASY: A Web-Based Framework for Integrative Analysis of Multi-Omics Cancer Datasets.

High-throughput transcriptomic and proteomic analyses are now routinely applied to study cancer biology. However, complex omics integration remains challenging and often time-consuming. Here, we developed DRPPM-EASY, an R Shiny framework for integrative multi-omics analysis. We applied our application to analyze RNA-seq data generated from a USP7 knockdown in T-cell acute lymphoblastic leukemia (T-ALL) cell line, which identified upregulated expression of a TAL1-associated proliferative signature in T-cell acute lymphoblastic leukemia cell lines. Next, we performed proteomic profiling of the USP7 knockdown samples. Through DRPPM-EASY-Integration, we performed a concurrent analysis of the transcriptome and proteome and identified consistent disruption of the protein degradation machinery and spliceosome in samples with USP7 silencing. To further illustrate the utility of the R Shiny framework, we developed DRPPM-EASY-CCLE, a Shiny extension preloaded with the Cancer Cell Line Encyclopedia (CCLE) data. The DRPPM-EASY-CCLE app facilitates the sample querying and phenotype assignment by incorporating meta information, such as genetic mutation, metastasis status, sex, and collection site. As proof of concept, we verified the expression of TP53 associated DNA damage signature in TP53 mutated ovary cancer cells. Altogether, our open-source application provides an easy-to-use framework for omics exploration and discovery.

World Health Organization and knowledge translation in maternal, newborn, child and adolescent health and nutrition.

The World Health Organization (WHO) has a mandate to promote maternal and child health and welfare through support to governments in the form of technical assistance, standards, epidemiological and statistical services, promoting teaching and training of healthcare professionals and providing direct aid in emergencies. The Strategic and Technical Advisory Group of Experts (STAGE) for maternal, newborn, child and adolescent health and nutrition (MNCAHN) was established in 2020 to advise the Director-General of WHO on issues relating to MNCAHN. STAGE comprises individuals from multiple low-income and middle-income and high-income countries, has representatives from many professional disciplines and with diverse experience and interests.Progress in MNCAHN requires improvements in quality of services, equity of access and the evolution of services as technical guidance, community needs and epidemiology changes. Knowledge translation of WHO guidance and other guidelines is an important part of this. Countries need effective and responsive structures for adaptation and implementation of evidence-based interventions, strategies to improve guideline uptake, education and training and mechanisms to monitor quality and safety. This paper summarises STAGE's recommendations on how to improve knowledge translation in MNCAHN. They include support for national and regional technical advisory groups and subnational committees that coordinate maternal and child health; support for national plans for MNCAHN and their implementation and monitoring; the production of a small number of consolidated MNCAHN guidelines to promote integrated and holistic care; education and quality improvement strategies to support guidelines uptake; monitoring of gaps in knowledge translation and operational research in MNCAHN.

Difference between kwashiorkor and marasmus: Comparative meta-analysis of pathogenic characteristics and implications for treatment.

Kwashiorkor and marasmus are two clinical syndromes observed in severe acute malnutrition. In this review, we highlighted the differences between these two syndromes by reviewing the data comparing kwashiorkor and marasmus in literature, combined with recent microbiological findings and meta-analysis. Depletion of antioxidants, vitamins and minerals were more severe in kwashiorkor than marasmus. This was consistent with the severe and uncontrolled oxidative stress associated with the depletion of gut anaerobes and the relative proliferation of aerotolerant gut pathogens. This relative proliferation and invasion of gut microbes belonging to the aerotolerant Proteobacteria phylum and pathogens suggested a specific microbial process critical in the pathogenesis of kwashiorkor. Liver mitochondrial and peroxisomal dysfunction could be secondary to toxic microbial compounds produced in the gut such as ethanol, lipopolysaccharides and endotoxins produced by Proteobacteria, particularly Klebsiella pneumoniae, and aflatoxin produced by Aspergillus species. The gut-liver axis alteration is characterized by oedema and a fatty and enlarged liver and was associated with a dramatic depletion of methionine and glutathione, an excessive level of free circulating iron and frequent lethal bacteraemia by enteric pathogens. This was consistent with the fact that antibiotics improved survival only in children with kwashiorkor but not marasmus. The specific pathogenic characteristics of kwashiorkor identified in this review open new avenues to develop more targeted and effective treatments for both marasmus and/or kwashiorkor. Urgent correction of plasma glutathione depletion, alongside supply of specific essential amino acids, particularly methionine and cysteine, early detection of pathogens and an antibiotic more efficient than amoxicillin in supressing gut Proteobacteria including K. pneumoniae, and probiotics to restore the human gut anaerobic mature microbiota could save many more children with kwashiorkor.

Unique characteristics of the type B aortic dissection patients with malperfusion in the Vascular Quality Initiative.

OBJECTIVE: Type B aortic dissection (TBAD) complicated by malperfusion carries high morbidity and mortality. The present study was undertaken to compare the characteristics of malperfusion and uncomplicated cohorts and to evaluate the long-term differences in survival using a granular, national registry. METHODS: Patients with TBAD entered into the thoracic endovascular aortic repair/complex endovascular aortic repair module of the Vascular Quality Initiative from 2010 to 2019 were included. The demographic, radiographic, operative, postoperative, in-hospital, and long-term reintervention data were compared between the malperfusion and uncomplicated TBAD groups using t tests and χ2 analysis, as appropriate. Overall survival was compared using Cox regression to generate survival curves. RESULTS: Of the 2820 included patients, 2267 had uncomplicated TBAD and 553 had malperfusion. The patients with malperfusion were younger (age, 55.8 vs 61.2 years; P < .001), were more often male (79.7% vs 68.1%; P < .001), had a higher preoperative creatinine (1.8 vs 1.1 mg/dL; P < .001), had more often presented with an American Society of Anesthesiologists class of 4 or 5 (81.9% vs 58.4%; P < .001), and had more often presented with urgent status (77.4% vs 32.8%; P < .001). In contrast, the uncomplicated TBAD group had had more medical comorbidities, including coronary artery disease and chronic obstructive pulmonary disease, and a larger aortic diameter (4.0 cm vs 4.9 cm; P < .001). The malperfusion group more frequently had proximal zones of disease in zones 0 to 2 (38.6% vs 31.5%; P = .002) and distal zones of disease in zones 9 and above (78.7% vs 46.2%; P < .001), with a greater number of aortic zones traversed (7.7 vs 5.1; P < .001) and a greater frequency of dissection extension into branch vessels (61.8% vs 23.1%; P < .001). Patients with malperfusion also exhibited greater case complexity, with a greater need for branch vessel stenting and longer procedure times. The overall incidence of postoperative complications was greater in the malperfusion group (39.4% vs 17.1%; P < .001) and included a greater rate of spinal cord ischemia (6.3% vs 2.2%; P < .001), acute kidney injury (10.4% vs 0.9%; P < .001), and in-hospital mortality (11.6% vs 5.6%; P < .001). In-hospital reintervention was also greater for the malperfusion patients (14.5% vs 7.4%; P < .001), although the incidence of long-term reinterventions was similar between the two groups (8.7% vs 9.7%; P = .548). A proximal zone of disease in zone 0 to 2 was associated with decreased survival. In contrast, a distal zone of disease in 9 and above, in-hospital reintervention, and long-term follow-up were associated with increased survival. Despite these differences, long-term survival did not differ between the malperfusion and uncomplicated groups (P = .320.) CONCLUSIONS: Patients presenting with TBAD and malperfusion represent a unique cohort. Despite the greater need for branch vessel stenting and in-hospital reintervention, they had similar long-term reintervention rates and survival compared with those with uncomplicated TBAD. These data lend insight with regard to the observed differences between uncomplicated and malperfusion TBAD.

Effects of dual antiplatelet therapy on graft patency after lower extremity bypass.

OBJECTIVE: Current guidelines recommend single-agent antiplatelet therapy for patients with symptomatic peripheral artery disease and consideration of dual antiplatelet therapy (DAPT) after surgical revascularization. The objective of this study was both to explore prescribing patterns of single antiplatelet therapy vs DAPT after lower extremity bypass surgery and to investigate the effects of antiplatelet therapy on bypass graft patency. METHODS: A retrospective analysis of prospectively collected nonemergent infrainguinal lower extremity bypass operations entered in the national Vascular Quality Initiative (2003-2018) with captured long-term follow-up was performed. Patients discharged on aspirin monotherapy or DAPT were identified. Linear regression investigated temporal trends in antiplatelet use. Multivariable Cox regression investigated predictors of primary, primary assisted, and secondary patency. RESULTS: Of the 13,020 patients investigated, 52.2% were discharged on aspirin monotherapy and 47.8% on DAPT. The proportion of patients discharged on DAPT increased from 10.6% in 2003 to 60.6% in 2018 (P < .001). The DAPT cohort was younger, had higher rates of medical (hypertension, diabetes, congestive heart failure, chronic obstructive pulmonary disease) and atherosclerotic (coronary artery disease, prior coronary artery bypass graft or percutaneous coronary intervention, prior lower extremity intervention) comorbidities, and had higher risk bypass procedures (more distal targets, prior inflow bypass procedure, prosthetic conduit use). Multivariable Cox regression analysis did not show any difference between the DAPT and aspirin cohorts in primary patency (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.88-1.10; P = .78), primary assisted patency (HR, 0.93; 95% CI, 0.80-1.07; P = .30), or secondary patency (HR, 0.88; 95% CI, 0.74-1.06; P = .18). On subgroup analysis based on bypass conduit, DAPT was found to have a protective effect on patency only in the prosthetic bypass cohort (primary patency: HR, 0.81 [95% CI, 0.66-1.00; P = .05]; primary assisted patency: HR, 0.74 [95% CI, 0.58-0.94; P = .01]; and secondary patency: HR, 0.60 [95% CI, 0.44-0.82; P < .001]). No patency differences were observed on adjusted subgroup analysis for the other bypass conduits. CONCLUSIONS: A significant and increasing proportion of patients are discharged on DAPT after lower extremity bypass revascularization. These patients represent a higher risk cohort with more medical comorbidities and higher risk bypass features. After controlling for these differences, DAPT therapy had no beneficial effect on overall bypass graft patency or major adverse limb events. However, on subgroup analysis, DAPT was associated with improved bypass graft patency in patients receiving prosthetic bypass conduits. Further study is warranted to investigate optimal duration of DAPT therapy and its possible bleeding complications in prosthetic bypass patients.

Publisher Correction: Parallel evolution in the emergence of highly pathogenic avian influenza A viruses.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20006-5.

Parallel evolution in the emergence of highly pathogenic avian influenza A viruses.

Parallel molecular evolution and adaptation are important phenomena commonly observed in viruses. Here, we exploit parallel molecular evolution to understand virulence evolution in avian influenza viruses (AIV). Highly-pathogenic AIVs evolve independently from low-pathogenic ancestors via acquisition of polybasic cleavage sites. Why some AIV lineages but not others evolve in this way is unknown. We hypothesise that the parallel emergence of highly-pathogenic AIV may be facilitated by permissive or compensatory mutations occurring across the viral genome. We combine phylogenetic, statistical and structural approaches to discover parallel mutations in AIV genomes associated with the highly-pathogenic phenotype. Parallel mutations were screened using a statistical test of mutation-phenotype association and further evaluated in the contexts of positive selection and protein structure. Our resulting mutational panel may help to reveal new links between virulence evolution and other traits, and raises the possibility of predicting aspects of AIV evolution.

The evolution of open abdominal aortic aneurysm repair at a tertiary care center.

BACKGROUND: The characteristics of and indications for open abdominal aortic aneurysm (AAA) repair have evolved over time. We evaluated these trends through the experience at a tertiary care academic center. METHODS: A retrospective review was conducted for patients undergoing open AAA repair (inclusive of type IV thoracoabdominal aortic aneurysms) from 2005 to 2018 at an academic institution. Trends over time were evaluated using the Spearman test; Cox regression was used to determine predictors of mortality and to generate adjusted survival curves. RESULTS: There were 628 patients (71.5% male; 88.2% white) with a mean age of 70.5 ± 9.4 years who underwent open AAA repair with a mean aneurysm diameter of 6.2 ± 1.5 cm. The median length of stay was 10 days, and the median intensive care unit length of stay was 3 days. Urgent repair was undertaken in 21.1%; 22.3% were type IV thoracoabdominal aortic aneurysm repairs, and 9.9% were performed for explantation. Our series favored a retroperitoneal approach in the majority of cases (82.5%). The proximal clamp sites were supraceliac (46.1%), suprarenal (29.1%), and infrarenal (24.8%), with approximately a third requiring renal artery reimplantation. The average cross-clamp time was 25.5 ± 14.9 minutes; the mean renal ischemia time for supraceliac and suprarenal clamp sites was 28.4 ± 12.3 minutes and 23.5 ± 12.7 minutes, respectively. Postoperative renal dysfunction occurred in 19.6% of the overall cohort, with 6.2% requiring hemodialysis. Of those requiring postoperative hemodialysis, the majority (75%) received an urgent repair. The in-hospital mortality was 2.3% for elective cases vs 20.9% for urgent repair, and 29.8% of patients were discharged to rehabilitation, with an overall 30-day readmission rate of 7.9%. Over time, there were trends of increased aneurysm repair complexity, with decreasing infrarenal clamp sites, increasing supraceliac clamp sites, increasing proportion of explantations, and increasing need for bifurcated grafts. The acuity of aneurysm repair likewise changed, with the proportion of urgent repairs increasing over time, largely attributable to the rise in explantations. Clamp site influenced the frequency of perioperative complications. Urgent repairs and age at operation were associated with mortality, whereas mortality was not associated with need for explantation and clamp location. CONCLUSIONS: Aneurysm repair reflected increasing complexity over time, with the need for explantation among urgent repairs significantly on the rise. Urgency and clamp location independently predicted long-term mortality, even after adjustment for age. These findings underscore the changing landscape of open AAA repair in the current era.

The use of intravascular ultrasound in the treatment of type B aortic dissection with thoracic endovascular aneurysm repair is associated with improved long-term survival.

OBJECTIVE: Intravascular ultrasound (IVUS) examination is an integral technique used for treating type B aortic dissection (TBAD) because it verifies true lumen access. The purpose of this study was to evaluate the use of IVUS, to determine factors associated with IVUS use, and to investigate the potential survival benefit associated with IVUS in the treatment of TBAD. METHODS: A retrospective review of TEVARs performed for TBAD in the national Vascular Quality Initiative was performed from January 2010 to August 2018. Data collected included demographics, intraoperative and postoperative variables, and long-term mortality. Multivariable logistic regression evaluated variables associated with IVUS the use and mortality, and Cox regression was performed for adjusted survival analysis. RESULTS: In this study of 2686 patients, the average age was 60.4 years, 69.3% were male, and IVUS examination was used in 74.6% of cases. IVUS patients were younger (60.0 years vs 61.7 years; P = .004), more often male (72.1% vs 61.3%; P < .001), exhibited less coronary disease, but had higher preoperative creatinine (1.27 ± 0.89 mg/dL vs 1.14 ± 0.68 mg/dL; P < .001) and were more often treated in the acute setting (55.2% vs 49.7%; P = .03). Interestingly, there were no differences in contrast use (117.4 ± 77.6 mL vs 123.0 ± 81.90.1 mL; P = .11) or fluoroscopy time (20.3 ± 16.5 minutes vs 19.0 ± 22.1 minutes; P = .10). However, IVUS cases had a greater number of devices implanted (1.84 vs 1.65; P < .001), higher rates of Zone 0 to 2 proximal seal (43.9% vs 30.7%; P < .001), higher rates of distal seal zones beyond the diaphragm (53.9% vs 37.4%; P = .001), and larger proximal and distal graft diameters, with no differences in postoperative renal function. IVUS patients notably also had higher rates of follow-up imaging (61.3% vs 54.8%; P = .003), larger maximum aortic diameters at follow-up, and more reinterventions over time. The number of aortic devices (odds ratio [OR] 1.56; 95% confidence interval [CI], 1.24-1.97; P < .001), malperfusion indication (OR, 1.68; 95% CI, 1.17-2.42; P = .005) and distal seal zone beyond the diaphragm (OR, 1.64; 95% CI, 1.30-2.07; P < .001) were independently associated with IVUS use, whereas female gender showed a trend towards less IVUS use (OR, 0.79; 95% CI, 0.62-1.01; P = .063). Even after controlling for age, preoperative comorbidities, and postoperative complications like spinal cord ischemia, IVUS was associated with a 61% decrease in the odds of mortality (OR, 0.39; 95% CI, 0.20-0.78; P = .008), with a clear survival advantage shown in adjusted survival curves. CONCLUSIONS: IVUS examination was used in the majority of TBAD, although not universally. IVUS examination was used more often in acute TBAD and more complex aortic repairs, and was independently associated with improved long-term survival. Further study is needed to understand these patterns.

Malnutrition Predisposes to Endotoxin-Induced Edema and Impaired Inflammatory Response in Parenterally Fed Piglets.

BACKGROUND: Poor nutrition status is common among hospitalized children and children in low-income countries and may be associated with increased susceptibility to edema and infections. We hypothesized that poor nutrition status, established with a suboptimal composition of parenteral nutrition (PN), predisposes to endotoxemia-induced edema, oxidative stress, and dysregulated immune responses. METHODS: Using a 2 × 2 factorial design, 3-day-old piglets (n = 40) were given either optimal or suboptimal composition of PN for 7 days and then infused with either saline or lipopolysaccharide (LPS) for 9 hours to induce an acute-phase reaction. Abdominal tissue edema and blood markers of immunity, inflammation, and oxidative stress were assessed. RESULTS: Piglets receiving suboptimal nutrition showed signs of malnutrition with restricted growth, signs of inflammation (elevated C-reactive protein [CRP], interleukin-6, and serum amyloid A levels), oxidative stress (lower erythrocyte glutathione/hemoglobin and α-tocopherol/cholesterol ratios), and liver dysfunction (increased liver weight and blood bilirubin levels). Perirenal edema was more excessive in malnourished LPS-infused animals, relative to healthy LPS-infused control animals (P < .01). Malnutrition reduced the inflammatory response to LPS (lower CRP, tumor necrosis factor-α, haptoglobin, and neutrophil to lymphocyte ratio) but did not influence LPS-induced oxidative stress markers. CONCLUSIONS: We conclude that endotoxemia and malnutrition in combination lead to acute-phase hyporesponsiveness and perirenal edema in piglets. This finding may have implications for pediatric patients that suffer from malnutrition, as their response to bacterial infections may differ substantially from patients of normal nutrition status.

Evolutionary Analyses of Base-Pairing Interactions in DNA and RNA Secondary Structures.

Pairs of nucleotides within functional nucleic acid secondary structures often display evidence of coevolution that is consistent with the maintenance of base-pairing. Here, we introduce a sequence evolution model, MESSI (Modeling the Evolution of Secondary Structure Interactions), that infers coevolution associated with base-paired sites in DNA or RNA sequence alignments. MESSI can estimate coevolution while accounting for an unknown secondary structure. MESSI can also use graphics processing unit parallelism to increase computational speed. We used MESSI to infer coevolution associated with GC, AU (AT in DNA), GU (GT in DNA) pairs in noncoding RNA alignments, and in single-stranded RNA and DNA virus alignments. Estimates of GU pair coevolution were found to be higher at base-paired sites in single-stranded RNA viruses and noncoding RNAs than estimates of GT pair coevolution in single-stranded DNA viruses. A potential biophysical explanation is that GT pairs do not stabilize DNA secondary structures to the same extent that GU pairs do in RNA. Additionally, MESSI estimates the degrees of coevolution at individual base-paired sites in an alignment. These estimates were computed for a SHAPE-MaP-determined HIV-1 NL4-3 RNA secondary structure. We found that estimates of coevolution were more strongly correlated with experimentally determined SHAPE-MaP pairing scores than three nonevolutionary measures of base-pairing covariation. To assist researchers in prioritizing substructures with potential functionality, MESSI automatically ranks substructures by degrees of coevolution at base-paired sites within them. Such a ranking was created for an HIV-1 subtype B alignment, revealing an excess of top-ranking substructures that have been previously identified as having structure-related functional importance, among several uncharacterized top-ranking substructures.

Contained rupture of arch aneurysm managed with total arch, frozen elephant trunk and endograft.

We here describe a complex case of a 75-year-old man presenting with contained rupture of an aortic arch aneurysm in the presence of a second thoracic aortic aneurysm. He was managed with emergent total arch replacement with frozen elephant trunk. Another stent-graft was used to achieve hemostasis at the distal anastomosis. He later underwent TEVAR extension to manage his second aneurysm in a staged fashion. This case demonstrates a number of important concepts in the evolving interaction between open and endovascular therapies of the aortic arch, particularly in the emergent setting.

A structural basis for antibody-mediated neutralization of Nipah virus reveals a site of vulnerability at the fusion glycoprotein apex.

Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes frequent outbreaks of severe neurologic and respiratory disease in humans with high case fatality rates. The 2 glycoproteins displayed on the surface of the virus, NiV-G and NiV-F, mediate host-cell attachment and membrane fusion, respectively, and are targets of the host antibody response. Here, we provide a molecular basis for neutralization of NiV through antibody-mediated targeting of NiV-F. Structural characterization of a neutralizing antibody (nAb) in complex with trimeric prefusion NiV-F reveals an epitope at the membrane-distal domain III (DIII) of the molecule, a region that undergoes substantial refolding during host-cell entry. The epitope of this monoclonal antibody (mAb66) is primarily protein-specific and we observe that glycosylation at the periphery of the interface likely does not inhibit mAb66 binding to NiV-F. Further characterization reveals that a Hendra virus-F-specific nAb (mAb36) and many antibodies in an antihenipavirus-F polyclonal antibody mixture (pAb835) also target this region of the molecule. Integrated with previously reported paramyxovirus F-nAb structures, these data support a model whereby the membrane-distal region of the F protein is targeted by the antibody-mediated immune response across henipaviruses. Notably, our domain-specific sequence analysis reveals no evidence of selective pressure at this region of the molecule, suggestive that functional constraints prevent immune-driven sequence variation. Combined, our data reveal the membrane-distal region of NiV-F as a site of vulnerability on the NiV surface.

Severe acute malnutrition and mortality in children in the community: Comparison of indicators in a multi-country pooled analysis.

OBJECTIVES: This study aims to describe the mortality risk of children in the community who had severe acute malnutrition (SAM) defined by either a mid-upper arm circumference (MUAC) <115mm, a low weight-for-height Z-score (WHZ) <-3 or both criteria. METHODS: We pooled individual-level data from children aged 6-59 months enrolled in 3 community-based studies in the Democratic Republic of the Congo (DRC), Senegal and Nepal. We estimate the mortality hazard using Cox proportional hazard models in groups defined by either anthropometric indicator. RESULTS: In total, we had 49,001 time points provided by 15,060 children available for analysis, summing to a total of 143,512 person-months. We found an increasing death rate with a deteriorating nutritional status for all anthropometrical indicators. Children identified as SAM only by a low MUAC (<115mm) and those identified only by a low WHZ (Z-score <-3) had a similar mortality hazard which was about 4 times higher than those without an anthropometric deficit. Having both a low MUAC and a low WHZ was associated with an 8 times higher hazard of dying compared to children within the normal range. The 2 indicators identified a different set of children; the proportion of children identified by both indicators independently ranged from 7% in the DRC cohort, to 35% and 37% in the Senegal and the Nepal cohort respectively. CONCLUSION: In the light of an increasing popularity of using MUAC as the sole indicator to identify SAM children, we show that children who have a low WHZ, but a MUAC above the cut-off would be omitted from diagnosis and treatment despite having a similar risk of death.

Long-read amplicon denoising.

Long-read next-generation amplicon sequencing shows promise for studying complete genes or genomes from complex and diverse populations. Current long-read sequencing technologies have challenging error profiles, hindering data processing and incorporation into downstream analyses. Here we consider the problem of how to reconstruct, free of sequencing error, the true sequence variants and their associated frequencies from PacBio reads. Called 'amplicon denoising', this problem has been extensively studied for short-read sequencing technologies, but current solutions do not always successfully generalize to long reads with high indel error rates. We introduce two methods: one that runs nearly instantly and is very accurate for medium length reads and high template coverage, and another, slower method that is more robust when reads are very long or coverage is lower. On two Mock Virus Community datasets with ground truth, each sequenced on a different PacBio instrument, and on a number of simulated datasets, we compare our two approaches to each other and to existing algorithms. We outperform all tested methods in accuracy, with competitive run times even for our slower method, successfully discriminating templates that differ by a just single nucleotide. Julia implementations of Fast Amplicon Denoising (FAD) and Robust Amplicon Denoising (RAD), and a webserver interface, are freely available.

Contained rupture of arch aneurysm managed with total arch, frozen elephant trunk and endograft.

We here describe a complex case of a 75-year-old man presenting with contained rupture of an aortic arch aneurysm in the presence of a second thoracic aortic aneurysm. He was managed with emergent total arch replacement with frozen elephant trunk. Another stent-graft was used to achieve hemostasis at the distal anastomosis. He later underwent TEVAR extension to manage his second aneurysm in a staged fashion. This case demonstrates a number of important concepts in the evolving interaction between open and endovascular therapies of the aortic arch, particularly in the emergent setting.

Trends in inferior vena cava filter placement and retrieval at a tertiary care institution.

OBJECTIVE: The aim of this study was to examine practice patterns of inferior vena cava (IVC) filter insertion and retrieval at a tertiary care institution. METHODS: A retrospective review of all IVC filter procedures performed at the University of Pennsylvania and entered into the Penn cohort of the Vascular Quality Initiative registry between January 2013 and September 2017 was performed. Data collected included demographics, venous thromboembolism risk factors, indications for filter placement, and presence and timing of retrieval. Trend analysis and multivariable logistic regression were performed to evaluate factors associated with failure to retrieve the filter. RESULTS: During the study period, 627 IVC filters were inserted. The mean age was 52.8 ± 16.9 years, and 49.3% were male; 39.2% were placed for a major indication, whereas 58.1% were placed for prophylaxis. There was a significant decline in overall frequency of filter placement during the period observed, with a 33% decrease from 2015 to 2016 and a 26% decrease from 2016 to 2017 (P < .001), with an overall retrieval rate of 44.9%. In contrast, there was a corresponding increase in filter retrieval, with a 20% increase in 2015 and a 68% increase in 2016 (P = .02). In evaluating trends separated by indication, there was a significant decline in prophylactic filter placement (P < .001) and a trend toward an increase in retrieval of prophylactic filters (P = .09). Whereas there was not a significant change in number of filter insertions for major indication (P = .06), filter retrievals for major indication filters increased (P = .01). Multivariable regression analysis revealed that longer time to follow-up (odds ratio [OR], 1.08; P < .001) and discharge to rehabilitation facility (OR, 6.14; P < .001) were predictive of failure to retrieve the filter. In contrast, filter placement at a later date within our study period (OR, 0.90; P < .001) and prophylactic indication for filter placement (OR, 0.36; P < .001) were protective from filter nonretrieval. CONCLUSIONS: These results show both a decline in overall IVC filter placement and an increase in overall IVC filter retrieval at our institution. These trends are predominantly due to a decrease in prophylactic filter placement as well as an overall increase in filter retrieval. Further study should be dedicated to increasing the retrieval rate in this population of patients.

Length of Stay after Thoracic Endovascular Aortic Repair Depends on Indication and Acuity.

BACKGROUND: Length of stay (LOS) is a commonly used metric to optimize value in medical care. Although pathways have been developed for some procedures in vascular surgery to reduce LOS, they do not yet exist for thoracic endovascular aortic repair (TEVAR). The purpose of this study is to identify and define the risk factors for prolonged LOS in patients undergoing TEVAR to facilitate pathway development. METHODS: We included TEVAR patients in the National Surgical Quality Improvement Program database from 2005 to 2015. Prolonged LOS was defined as LOS > 75th percentile of the overall cohort (11 days). Because initial analysis revealed the distinct clinical differences between dissection and aneurysm patients, further analysis was stratified by aortic pathology. Student's t-test and Chi-square tests were used to compare demographic and perioperative variables between dissection and aneurysm patients, respectively. Multivariable logistic regression was used to evaluate the predictors for prolonged LOS. RESULTS: A total of 3,021 patients underwent TEVAR, with 858 patients (28.4%) undergoing TEVAR for dissection and 2,163 (71.6%) undergoing TEVAR for aneurysm. An initial analysis with logistic regression identified dissection indication (odds ratio [OR], 2.87; 95% confidence interval [CI], 1.1-7.3) as an independent predictor of prolonged LOS. Further analysis for prolonged LOS was subsequently performed separating dissection and aneurysm patients. Aneurysm patients were older (71.2 ± 11.7 vs. 63.1 ± 13.6 years, P < 0.001), more often Caucasian (76.8% vs. 61.8%, P < 0.001), and had more medical comorbidities (chronic obstructive pulmonary disease, cardiac history, diabetes, peripheral vascular disease, transient ischemic attack [TIA], P < 0.001). In contrast, dissection patients had higher American Society of Anesthesiology (ASA) classification score (58.5% had >3 ASA vs. 45.5%, P < 0.001), longer hospitalizations (10.2 ± 9.3 vs. 8.5 ± 10.4 days, P < 0.001), were more likely to have been transferred from another hospital or emergency room (58.4% vs. 48.3%, P < 0.001), and were more often emergent (32.4% vs. 15.4%, P < 0.001). In dissection patients, ASA classification score (OR, 1.49; 95% CI, 1.1-2.1) and dialysis (OR, 1.98; 95% CI, 1.0-3.9) were independent predictors for prolonged LOS. In aneurysm patients, dependent functional status (OR, 2.03; 95% CI, 1.4-2.8), diabetes (OR, 1.75; 95% CI, 1.1-2.8), cardiac history (OR, 1.37; 95% CI, 1.0-1.9), emergency status (OR, 1.98; 95% CI, 1.4-2.8), and dialysis (OR, 2.08; 95% CI, 1.2-3.7) predicted prolonged LOS. Postoperative complications including stroke/TIA; failure to wean from ventilator, sepsis, and pneumonia; and need for reoperation similarly increased LOS in both dissection and aneurysm patients. CONCLUSIONS: Dissection and aneurysm patients undergoing TEVAR are comprised of different patient populations, with dissection patients more often enduring prolonged hospitalizations. In contrast, TEVAR performed for nonemergent aneurysm repair had the shortest LOS. These data support the development of separate pathways defined by indication and acuity for patients undergoing TEVAR.

Severely malnourished children with a low weight-for-height have similar mortality to those with a low mid-upper-arm-circumference: II. Systematic literature review and meta-analysis.

BACKGROUND: The WHO recommended criteria for diagnosis of sever acute malnutrition (SAM) are weight-for-height/length Z-score (WHZ) of <- 3Z of the WHO2006 standards, a mid-upper-arm circumference (MUAC) of < 115 mm, nutritional oedema or any combination of these parameters. A move to eliminate WHZ as a diagnostic criterion has been made on the assertion that children with a low WHZ are healthy, that MUAC is a "superior" prognostic indicator of mortality and that adding WHZ to the assessment does not improve the prediction of death. Our objective was to examine the literature comparing the risk of death of SAM children admitted by WHZ or MUAC criteria. METHODS: We conducted a systematic search for reports which examined the relationship of WHZ and MUAC to mortality for children less than 60 months. The WHZ, MUAC, outcome and programmatic variables were abstracted from the reports and examined. Individual study's case fatality rates were compared by chi-squared analysis and random effects meta-analyses for combined data. RESULTS: Twenty-one datasets were reviewed. All the patient studies had an ascertainment bias. Most were inadequate because they had insufficient deaths, used obsolete standards, combined oedematous and non-oedematous subjects, did not report the proportion of children with both deficits or the deaths occurred remotely after anthropometry. The meta-analyses showed that the mortality risks for children who have SAM by MUAC < 115 mm only and those with SAM by WHZ < -3Z only are not different. CONCLUSIONS: As the diagnostic criteria identify different children, this analysis does not support the abandonment of WHZ as an important independent diagnostic criterion for the diagnosis of SAM. Failure to identify such children will result in their being denied treatment and unnecessary deaths from SAM.