Thrombosis in COVID 2022: An Updated Narrative Review of Current Literature and Inpatient Management.

Early in the pandemic, it was recognized that infection with COVID-19 was associated with an increased incidence in both venous and arterial thrombotic events leading to poor patient outcomes. Given the rapid rise of the pandemic, anticoagulation strategies were initially based upon retrospective and observational data with few high-quality randomized control trials to help direct strategies regarding the use of thromboprophylaxis during hospitalization, empiric therapeutic anticoagulation, and extended-duration thromboprophylaxis after discharge. Over the past year, several randomized control trials have now been published evaluating these strategies. In this article, we hope to review the current literature surrounding the use of intermediate-dose thromboprophylaxis, empiric therapeutic anticoagulation, and the use of extended-duration thromboprophylaxis for patients hospitalized with COVID-19.

Analysis of Hematology and Oncology Fellowship Website Content and Diversity Representation.

PURPOSE: Hematology and oncology (HO) lags behind all medicine subspecialties in fellows under-represented in medicine (URM) despite a growing minority patient population. Websites have been effectively used in URM recruitment. We evaluated all US HO program websites to facilitate a more informed and URM-considerate recruitment. We also performed a stratified analysis on programs affiliated with National Cancer Institute (NCI) Designated Cancer Centers, National Comprehensive Cancer Center Network (NCCN) member institutions, and ranked as a top 50 cancer hospital by US News, given their stated commitment to outreach. MATERIALS AND METHODS: Websites of all 2019-2020 Accreditation Council for Graduate Medical Education-accredited HO programs were assessed for 28 informational and three diversity categories. Websites with > 70% of categories were comprehensive. Affiliation with NCI, NCCN, and US News was noted. RESULTS: One hundred fifty-six websites were analyzed: 20% were comprehensive and 22% had any diversity information. Inclusion of diversity content and being comprehensive were significantly associated (P = .001). NCI, NCCN, and US News ranking were significantly associated with inclusion of more information in univariate analyses (P < .001, P = .008, and P < .001, respectively). Multivariate analyses showed that US News ranking was significantly associated with more information (P = .005). Diversity-related univariate and multivariate analyses showed a significant association with US News ranking (P = .006 and P = .029, respectively). CONCLUSION: Most HO fellowship websites are not comprehensive and lack diversity content. Given COVID-19 travel restrictions limit in-person interviews, digital program presence remains an important opportunity. HO programs should offer comprehensive and inclusive websites to better inform applicants, including URM. This may increase institutional diversity and potentially improve URM representation in the HO workforce.

Neuraxial anaesthesia is associated with improved outcomes and reduced postoperative complications in patients undergoing aseptic revision total hip arthroplasty.

BACKGROUND: As the incidence of primary total hip arthroplasty (THA) continues to increase, revision THA (rTHA) is becoming an increasingly common procedure. rTHA is widely regarded as a more challenging procedure, with higher complication rates and increased medical, social and economic burdens when compared to its primary counterpart. Given the complexity of rTHA and the projected increase in incidence of these procedures, patient optimisation is becoming of interest to improve outcomes. Anaesthetic choice has been extensively studied in primary THA as a modifiable risk factor for postoperative outcomes, showing favourable results for neuraxial anaesthesia compared to general anaesthesia. The impact of anaesthetic choice in rTHA has not been studied previously. METHODS: A retrospective study was performed using the American College of Surgeons National Surgical Quality Improvement Program database. Patients who underwent rTHA between 2014 and 2017 were divided into 3 anaesthesia cohorts: general anaesthesia, neuraxial anaesthesia, and combined general-regional (neuraxial and/or peripheral nerve block) anaesthesia. Univariate and multivariate analyses were used to analyse patient characteristics and 30-day postoperative outcomes. Bonferroni correction was applied for post-hoc analysis. RESULTS: In total, 5759 patients were identified. Of these, 3551 (61.7%) patients underwent general anaesthesia, 1513 (26.3%) patients underwent neuraxial anaesthesia, and 695 (12.1%) patients underwent combined general-regional anaesthesia. On multivariate analysis, neuraxial anaesthesia was associated with decreased odds for any-one complication (OR 0.635; p < 0.001), perioperative blood transfusion (OR 0.641; p < 0.001), and extended length of stay (OR 0.005; p = 0.005) compared to general anaesthesia. CONCLUSIONS: Relative to those receiving general anaesthesia, patients undergoing neuraxial anaesthesia are at decreased risk for postoperative complications, perioperative blood transfusions, and extended length of stay. Prospective controlled trials should be conducted to verify these findings.

Association of Anesthesia Type with Postoperative Outcome and Complications in Patients Undergoing Revision Total Knee Arthroplasty.

Revision total knee arthroplasty (TKA) is an increasingly common procedure and is effective in treating knee osteoarthritis, but it has higher complication rates than primary TKA. Anesthetic choice poses perioperative risk that has been extensively studied in primary TKA, showing favorable results for regional anesthesia compared with general anesthesia. The impact of anesthetic choice in revision TKAs is not well studied. A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program database. Patients who underwent revision TKAs between 2014 and 2017 were divided into three anesthesia cohorts: (1) general anesthesia, (2) regional anesthesia, and (3) combined general-regional anesthesia. Univariate and multivariate analyses were used to analyze patient characteristics and 30-day postoperative outcomes. Bonferroni correction was applied for post hoc analysis. In total, 8,820 patients were identified. Of whom, 3,192 patients underwent general anesthesia, 3,474 patients underwent regional anesthesia, and 2,154 patients underwent combined anesthesia. After multivariate analyses, regional anesthesia was associated with decreased odds for any complication (p = 0.008), perioperative blood transfusion (p < 0.001), and extended length of stay (p < 0.001) compared with general anesthesia. In addition, regional anesthesia was associated with decreased odds for perioperative blood transfusion (p < 0.001) and extended length of stay (p = 0.006) compared with combined anesthesia. However, following multivariate analysis, regional anesthesia was not associated with decreased odds of wound, pulmonary, renal, urinary tract, thromboembolic, and cardiac complications, and was not associated with return to operating room, extended length of stay, minor and major complications, and mortality. Retrospective analysis of a large surgical database suggests that patients receiving general anesthesia have increased likelihood for developing adverse postoperative outcomes relative to patients receiving regional anesthesia. Prospective and controlled trials should be conducted to verify these findings.

Does tumor profile in gastric and gastroesophageal (GE) junction cancer justify off-label use of targeted therapy?-a narrative review.

Despite significant therapeutic progress, gastric cancer remains among the most deadly forms of cancer encountered in clinical practice, and this remains true even in the context of declining incidence. Outcomes in advanced disease remain poor and therapy is rarely curative in this setting. As our understanding of tumor profile gains sophistication, a growing interest in targeted therapies and moreover the use of tumor profile to inform these therapies has developed in the hopes of altering nearly uniformly poor outcomes. A wide and growing array of molecular targets have been identified in the recent past. Targets of potential clinical interest include human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR), poly(ADP-ribose) polymerase (PARP), mammalian target of rapamycin (mTOR), c-MET, and fibroblast growth factor receptor (FGFR). This advanced molecular understanding has been increasingly used to justify the off-label usage of targeted therapies, though the efficacy of this approach warrants careful consideration. While targeted agents have demonstrated efficacy across a wide range of malignancies, even with molecular profiling data, efficacy is not assured. It will also be demonstrated that even within the same malignancy, what holds true in the metastatic setting does not necessarily apply to the adjuvant or neoadjuvant setting. This review will assess the current evidence for the use of targeted therapies utilizing these biomarkers in the context of gastric and gastroesophageal (GE) junction cancers.

Correction: In Porphyromonas gingivalis VimF Is Involved in Gingipain Maturation through the Transfer of Galactose.

[This corrects the article DOI: 10.1371/journal.pone.0063367.].

Genome Sequences of Bacteriophages KaiHaiDragon and OneinaGillian, Isolated from Microbacterium foliorum in Riverside, California.

KaiHaiDragon and OneinaGillian are two bacteriophages which have been recovered from soil samples using the bacterial host Microbacterium foliorum Their genome lengths are 52,992 bp and 61,703 bp, with 91 and 104 predicted open reading frames, respectively. KaiHaiDragon belongs to cluster EC, and OneinaGillian is a member of cluster EG.

Genome Sequence of JangDynasty, a Newly Isolated Mycobacteriophage.

JangDynasty is a bacteriophage that infects Mycobacterium smegmatis mc2155. It has a genome length of 70,883 bp, with 124 predicted open reading frames (ORFs), 42 of which have known functions. JangDynasty belongs to cluster O, and like other cluster O phages, it is a siphovirus with a prolate capsid.

In Porphyromonas gingivalis VimF is involved in gingipain maturation through the transfer of galactose.

Previously, we have reported that gingipain activity in Porphyromonas gingivalis, the major causative agent in adult periodontitis, is post-translationally regulated by the unique Vim proteins including VimF, a putative glycosyltransferase. To further characterize VimF, an isogenic mutant defective in this gene in a different P. gingivalis genetic background was evaluated. In addition, the recombinant VimF protein was used to further confirm its glycosyltransferase function. The vimF-defective mutant (FLL476) in the P. gingivalis ATCC 33277 genetic background showed a phenotype similar to that of the vimF-defective mutant (FLL95) in the P. gingivalis W83 genetic background. While hemagglutination was not detected and autoaggregation was reduced, biofilm formation was increased in FLL476. HeLa cells incubated with P. gingivalis FLL95 and FLL476 showed a 45% decrease in their invasive capacity. Antibodies raised against the recombinant VimF protein in E. coli immunoreacted only with the deglycosylated native VimF protein from P. gingivalis. In vitro glycosyltransferase activity for rVimF was observed using UDP-galactose and N-acetylglucosamine as donor and acceptor substrates, respectively. In the presence of rVimF and UDP-galactose, a 60 kDa protein from the extracellular fraction of FLL95 which was identified by mass spectrometry as Rgp gingipain, immunoreacted with the glycan specific mAb 1B5 antibody. Taken together, these results suggest the VimF glycoprotein is a galactosyltransferase that may be specific for gingipain glycosylation. Moreover, galatose is vital for the growing glycan chain.

Sialidase and sialoglycoproteases can modulate virulence in Porphyromonas gingivalis.

The Porphyromonas gingivalis recombinant VimA can interact with the gingipains and several other proteins, including a sialidase. Sialylation can be involved in protein maturation; however, its role in virulence regulation in P. gingivalis is unknown. The three sialidase-related proteins in P. gingivalis showed the characteristic sialidase Asp signature motif (SXDXGXTW) and other unique domains. To evaluate the roles of the associated genes, randomly chosen P. gingivalis isogenic mutants created by allelic exchange and designated FLL401 (PG0778::ermF), FLL402 (PG1724::ermF), and FLL403 (PG0352::ermF-ermAM) were characterized. Similar to the wild-type strain, FLL402 and FLL403 displayed a black-pigmented phenotype in contrast to FLL401, which was not black pigmented. Sialidase activity in P. gingivalis FLL401 was reduced by approximately 70% in comparison to those in FLL402 and FLL403, which were reduced by approximately 42% and 5%, respectively. Although there were no changes in the expression of the gingipain genes, their activities were reduced by 60 to 90% in all the isogenic mutants compared to that for the wild type. Immunoreactive bands representing the catalytic domains for RgpA, RgpB, and Kgp were present in FLL402 and FLL403 but were missing in FLL401. While adhesion was decreased, the capacity for invasion of epithelial cells by the isogenic mutants was increased by 11 to 16% over that of the wild-type strain. Isogenic mutants defective in PG0778 and PG0352 were more sensitive to hydrogen peroxide than the wild type. Taken together, these results suggest that the P. gingivalis sialidase activity may be involved in regulating gingipain activity and other virulence factors and may be important in the pathogenesis of this organism.

Role of vimA in cell surface biogenesis in Porphyromonas gingivalis.

The Porphyromonas gingivalis vimA gene has been previously shown to play a significant role in the biogenesis of gingipains. Further, in P. gingivalis FLL92, a vimA-defective mutant, there was increased auto-aggregation, suggesting alteration in membrane surface proteins. In order to determine the role of the VimA protein in cell surface biogenesis, the surface morphology of P. gingivalis FLL92 was further characterized. Transmission electron microscopy demonstrated abundant fimbrial appendages and a less well defined and irregular capsule in FLL92 compared with the wild-type. In addition, atomic force microscopy showed that the wild-type had a smoother surface compared with FLL92. Western blot analysis using anti-FimA antibodies showed a 41 kDa immunoreactive protein band in P. gingivalis FLL92 which was missing in the wild-type P. gingivalis W83 strain. There was increased sensitivity to globomycin and vancomycin in FLL92 compared with the wild-type. Outer membrane fractions from FLL92 had a modified lectin-binding profile. Furthermore, in contrast with the wild-type strain, nine proteins were missing from the outer membrane fraction of FLL92, while 20 proteins present in that fraction from FLL92 were missing in the wild-type strain. Taken together, these results suggest that the VimA protein affects capsular synthesis and fimbrial phenotypic expression, and plays a role in the glycosylation and anchorage of several surface proteins.