Metagenomic assessment of gut microbial communities and risk of severe COVID-19.

BACKGROUND: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. METHODS: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. RESULTS: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. CONCLUSIONS: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.

Metagenomic assessment of gut microbial communities and risk of severe COVID-19.

The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. We profiled 127 hospitalized patients with COVID-19 (n=79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. 48 species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID", suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with predicting whether stool was obtained from patients with severe vs. moderate COVID-19. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to validate these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.

Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe.

Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.

A novel MC1R allele for black coat colour reveals the Polynesian ancestry and hybridization patterns of Hawaiian feral pigs.

Pigs (Sus scrofa) have played an important cultural role in Hawaii since Polynesians first introduced them in approximately AD 1200. Additional varieties of pigs were introduced following Captain Cook's arrival in Hawaii in 1778 and it has been suggested that the current pig population may descend primarily, or even exclusively, from European pigs. Although populations of feral pigs today are an important source of recreational hunting on all of the major islands, they also negatively impact native plants and animals. As a result, understanding the origins of these feral pig populations has significant ramifications for discussions concerning conservation management, identity and cultural continuity on the islands. Here, we analysed a neutral mitochondrial marker and a functional nuclear coat colour marker in 57 feral Hawaiian pigs. Through the identification of a new mutation in the MC1R gene that results in black coloration, we demonstrate that Hawaiian feral pigs are mostly the descendants of those originally introduced during Polynesian settlement, though there is evidence for some admixture. As such, extant Hawaiian pigs represent a unique historical lineage that is not exclusively descended from feral pigs of European origin.

Effects of hyperbaric oxygen on the replanted extremity subjected to prolonged warm ischaemia.

In this investigation, the influence of hyperbaric oxygen (HBO) therapy on the survival of a replanted extremity subjected to prolonged warm ischaemia is evaluated. Among the relative contraindications to replantation are prolonged warm ischaemia time, since an obstruction to blood reflow ('no-reflow phenomenon') may occur in amputated parts that are subjected to more than 6h of warm ischaemia. Twenty-three rat hindlimbs were amputated and subjected to 4h of normothermic ischaemia. The average weight of the animals was 500 gm, and re-plantation of the hindlimb was performed by bone fixation followed by microvascular anastomosis of the femoral vessels. Limb re-vascularisation was confirmed at the end of all procedures by the milk test, clinical assessment and pulse oximetry recordings (>90%). Eleven animals served as a control group and no further therapy was instituted, whereas 12 animals served as the study (replantation) group and were subjected to HBO therapy for 3 days postoperatively. The therapy was conducted in a large animal chamber for 90 min at 2.5 ata. Limb survival was assessed by capillary refill upon compression, skin turgor assessment and colour. Confirmation of clinical findings was conducted with daily pulse oximetry readings of >90%. Animals were followed up for 7 days at which point all animals were euthanized or were euthanized earlier if a non-viable limb was present. Two of the 11 limbs in the control group survived following re-plantation, whereas eight of the 12 limbs in the experimental HBO group survived at least 7 days following replantation. This difference was statistically significant (p=0.0361) using chi-square analysis and Fisher's exact test. Although re-plantation of an amputated extremity after prolonged warm ischaemia is considered a relative contraindication due to the possibility of poor outcomes, our results indicate that the window for replantation may be increased if adjunctive HBO therapy is employed in the postoperative period.

Pediatric trigger finger from calcific tendonitis.

In pediatric patients, triggering of digits other than the thumb is uncommon and can have unique etiology. We present a juvenile patient whose trigger finger was associated with a solid calcified nodule on the flexor digitorum superficialis tendon.

Conversion of a ring finger metacarpophalangeal joint arthrodesis to arthroplasty: a case report.

This case report presents the conversion of a ring finger metacarpophalangeal joint arthrodesis to arthroplasty, using a pyrocarbon implant. The patient sought a conversion secondary to poor grip strength and inability to perform basic tasks in his job with the Marine Corps. Three months after surgery he had a stable joint and a 50% increase in grip strength.

Assessment of four midcarpal radiologic determinations.

Several radiologic measurement methods have been described for determining static carpal alignment of the wrist. These include the scapholunate, radiolunate, and capitolunate angles. The triangulation method is an alternative radiologic measurement which we believe is easier to use and more reproducible and reliable than the above mentioned methods. The purpose of this study is to assess the intraobserver reproducibility and interobserver reliability of the triangulation method, scapholunate, radiolunate, and capitolunate angles. Twenty orthopaedic residents and staff at varying levels of training made four radiologic measurements including the scapholunate, radiolunate and capitolunate angles as well as the triangulation method on five different lateral, digitized radiographs of the wrist and forearm in neutral radioulnar deviation. Thirty days after the initial measurements, the participants repeated the four radiologic measurements using the same radiographs. The triangulation method had the best intra-and-interobserver agreement of the four methods tested. This agreement was significantly better than the capitolunate and radiolunate angles. The scapholunate angle had the next best intraobserver reproducibility and interobserver reliability. The triangulation method has the best overall observer agreement when compared to the scapholunate, radiolunate, and capitolunate angles in determining static midcarpal alignment. No comment can be made on the validity of the measurements since there is no radiographic gold standard in determining static carpal alignment.

Constraint in primary total knee arthroplasty.

Instability is an important cause of failure following total knee arthroplasty. Increasing component constraint may reduce instability, but doing so also can cause increased forces to be transmitted to fixation and implant interfaces, which may lead to premature aseptic loosening. Constraint is defined as the effect of the elements of knee implant design that provides the stability needed to counteract forces about the knee after arthroplasty in the presence of a deficient soft-tissue envelope. Determining the amount of constraint necessary can be challenging. Most primary total knee arthroplasties are performed for knees without substantial deformity or the need for difficult ligament balancing; in these cases, either a posterior-stabilized or a posterior cruciate-retaining design is appropriate. In certain situations, such as patients with prior patellectomies, rheumatoid arthritis, or substantial preoperative deformities, a posterior-stabilized knee may be favored. With their large posts, varus-valgus constrained implants typically are reserved for patients with substantial coronal plane instability, which is difficult to balance with a posterior-stabilized or cruciate-retaining implant alone. Rotating-hinge knee implants usually are recommended for patients with severe deformity or instability that cannot be managed with a varus-valgus implant.

A technical note on percutaneous scaphoid fixation using a hybrid technique.

This article describes a percutaneous fixation technique for a midwaist scaphoid fracture using an antegrade (dorsal) guidewire and a retrograde (volar) cannulated screw placement. This simplified hybrid technique allows for accurate dorsal central wire placement and stable internal fixation with minimal violation of the articular cartilage of the proximal pole of the scaphoid.