How Support of Early Career Researchers Can Reset Science in the Post-COVID19 World.

The COVID19 crisis has magnified the issues plaguing academic science, but it has also provided the scientific establishment with an unprecedented opportunity to reset. Shoring up the foundation of academic science will require a concerted effort between funding agencies, universities, and the public to rethink how we support scientists, with a special emphasis on early career researchers.

Apirhabdus apintestini gen. nov., sp. nov., a member of a novel genus of the family Enterobacteriaceae, isolated from the gut of the western honey bee Apis mellifera.

A Gram-negative, motile, rod-shaped bacterial strain, CA-0114T, was isolated from the midgut of a western honey bee, Apis mellifera. The isolate exhibited ≤96.43 % 16S rRNA gene sequence identity (1540 bp) to members of the families Enterobacteriaceae and Erwiniaceae. Phylogenetic trees based on genome blast distance phylogeny and concatenated protein sequences encoded by conserved genes atpD, fusA, gyrB, infB, leuS, pyrG and rpoB separated the isolate from other genera forming a distinct lineage in the Enterobacteriaceae. In both trees, the closest relatives were Tenebrionicola larvae YMB-R21T and Tenebrionibacter intestinalis BIT-L3T, which were isolated previously from Tenebrio molitor L., a plastic-eating mealworm. Digital DNA-DNA hybridization, orthologous average nucleotide identity and average amino acid identity values between strain CA-0114T and the closest related members within the Enterobacteriaceae were ≤23.1, 75.45 and 76.04 %, respectively. The complete genome of strain CA-0114T was 4 451669 bp with a G+C content of 52.12 mol%. Notably, the apparent inability of strain CA-0114T to ferment d-glucose, inositol and l-rhamnose in the API 20E system is unique among closely related members of the Enterobacteriaceae. Based on the results obtained through genotypic and phenotypic analysis, we propose that strain CA-0114T represents a novel species and genus within the family Enterobacteriaceae, for which we propose the name Apirhabdus apintestini gen. nov., sp. nov. (type strain CA-0114T=ATCC TSD-396T=DSM 116385T).

In Patients With Rotator Cuff Tears, Female, Hispanic, African American, Asian, Socially Deprived, Federally Insured, and Uninsured Patients Are Less Commonly Treated Surgically.

PURPOSE: The purpose of the current study was to evaluate socioeconomic factors affecting whether a patient undergoes rotator cuff repair after a diagnosis of a rotator cuff tear. METHODS: From 2009 through 2018, claims for adult (≥18 years of age) patients who were diagnosed with a primary rotator cuff injury were identified in the New York Statewide Planning and Research Cooperative System (SPARCS) database via International Classification of Diseases (ICD)-9th Revision-Clinical Modification (CM) and ICD-10-CM diagnostic codes. SPARCS is a comprehensive all-payer database collecting all inpatient and outpatient pre-adjudicated claims in New York. ICD-9-CM and ICD-10-CM codes were used to identify the initial diagnosis for each patient. Current Procedural Terminology codes were used to identify subsequent rotator cuff surgery. The procedures identified were linked with the initial diagnosis, and patients were noted as either having or not having rotator cuff surgery. Logistic regression analysis was performed for variables including age, sex, race, Social Deprivation Index (SDI), Charlson Comorbidity Index, and primary insurance type to determine the effect of patient factors on the likelihood of having surgery after a diagnosis of rotator cuff injury. RESULTS: Of the 67,584 rotator cuff patients included in the analysis, 19,770 (29.3%) of the patients underwent surgical intervention. From the logistic regression, females relative to males (odds ratio [OR] = 0.798, P < .0001), increased SDI (OR = 0.994, p < .0001), African American compared with White race (OR = 0.694, P < .0001), Asian compared with White (OR = 0.832, P < .0001), Hispanic compared with White (OR = 0.693, P < .0001), other race (OR = 0.58, P < .0001), those with Medicare (OR = 0.601, P < .0001) or Medicaid (OR = 0.614, P < .0001) relative to private insurance, and self-pay relative to private insurance (OR = 0.727, P < .0001) were all associated with decreased odds of undergoing rotator cuff surgery. Older patients (OR = 1.012, P < .0001) and Workers' Compensation relative to private insurance (OR = 1.664, P < .0001) had increased odds of undergoing surgery. CONCLUSIONS: The results of the current study identified disparities in the likelihood of undergoing rotator cuff repair after a diagnosis of a rotator cuff tear based on patient demographic and socioeconomic factors. Individuals with higher SDI; African American, Asian, Hispanic, or other non-White races; and those with Medicare, Medicaid, or self-pay insurance had decreased odds of surgery, whereas older age and Workers' Compensation insurance were associated with increased odds of undergoing surgery. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Peroneus Longus Tendon Autograft May Present a Viable Alternative for Anterior Cruciate Ligament Reconstruction: A Systematic Review.

PURPOSE: To examine the available literature to better understand the objective and patient-reported outcomes using peroneus longus tendon (PLT) autograft compared with more commonly used autografts, such as the quadrupled hamstring tendons (HT), in patients undergoing primary for anterior cruciate ligament reconstruction (ACLR). METHODS: A comprehensive search of published literature in PubMed, Web of Science, Cochrane Library, Ovid, and EMBASE databases was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria included patients undergoing ACLR with PLT autograft, inclusion of patient-recorded outcome measures, and availability in English language. Publications that included only biomechanical analysis or ACLR with use of allograft or combination grafts were excluded. RESULTS: A total of 16 studies (Level of Evidence range: I-IV) met inclusion criteria, with follow-up ranging from 3 months to 5 years. In the available case series, patient-reported outcomes ranged from Lysholm = 80.7 to 95.1, International Knee Documentation Committee 78.1 to 95.7. In prospective cohorts and randomized controlled trials, PLT performance was comparable with HT autografts (PLT/HT: Lysholm = 88.3-95.1/86.5-94.9, International Knee Documentation Committee = 78.2-92.5/87.4-93.4). The majority of PLT grafts diameters were equal or greater than HT counterparts with a mean of >8 mm (PLT/HT: 7.0-9.0 mm/7.65-8.5 mm). There was minimal donor-site morbidity associated with PLT harvest. CONCLUSIONS: Although limitations exist within the available literature, existing evidence suggests that PLT autograft routinely produces adequately sized grafts with comparable early outcomes to HT autograft and low risk of donor-site morbidity. However, the PLT autograft is yet to demonstrate superiority to any of the more-traditional autograft selections. LEVEL OF EVIDENCE: Level IV, systematic review of Level I-IV studies.

Testosterone Replacement Therapy and Associated Rates of Trigger Finger, de Quervain Tenosynovitis, and Their Subsequent Management.

PURPOSE: Anabolic steroid therapy has been associated with tendon injury, but there is a paucity of evidence associating physiologic testosterone replacement therapy (TRT) with tenosynovitis of the hand, specifically trigger finger and de Quervain tenosynovitis. The purpose of this study was to evaluate the relationship between TRT and tenosynovitis of the hand. METHODS: This was a one-to-one exact matched retrospective cohort study using a large nationwide claims database. Records were queried between 2010 and 2019 for adult patients who filled a prescription for TRT for 3 consecutive months. Rates of new onset trigger finger and de Quervain tenosynovitis and subsequent steroid injection or surgery were identified using ICD-9, ICD-10, and Current Procedural Terminology billing codes. Single-variable chi-square analyses and multivariable logistic regression were used to compare rates in the TRT and control cohorts while controlling for potential confounding variables. Both unadjusted and adjusted odds ratios (OR) are reported for each comparison. RESULTS: In the adjusted analysis, patients undergoing TRT were more than twice as likely to develop trigger finger compared to their matched controls. TRT was also associated with an increased likelihood of experiencing de Quervain tenosynovitis. Of the patients diagnosed with either trigger finger or de Quervain tenosynovitis over the 2-year period, patients with prior TRT were roughly twice as likely to undergo steroid injections or surgical release for both trigger finger and de Quervain tenosynovitis compared to the controls. CONCLUSIONS: TRT is associated with an increased likelihood of both trigger finger and de Quervain tenosynovitis, and an increased likelihood of requiring surgical release for both conditions. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Decreased prevalence of new-onset adhesive capsulitis in patients prescribed angiotensin receptor blockers.

BACKGROUND: Angiotensin receptor blockers (ARBs) are commonly prescribed antihypertensive agents that have well-known antifibrotic properties. The purpose of this study was to examine the association between ARB use and the rates of new-onset adhesive capsulitis as well as adhesive capsulitis requiring operative treatment. METHODS: Using a large national insurance database, a randomly generated cohort of patients with at least 3 continuous months of ARB use between January 2010 and December 2019 (n = 1,000,000) was compared to a separate randomly generated cohort without ARB use (n = 3,000,000). Rates of newly diagnosed adhesive capsulitis and associated manipulation under anesthesia (MUA) and/or arthroscopic capsulotomy were calculated over a 1- and 2-year period following the completion of at least 3 continuous months of ARB therapy. Rates were compared using multivariable logistic regression to control for demographics and comorbidities. Both unadjusted and adjusted odds ratios and 95% confidence intervals were calculated and reported for each comparison. Statistical significance was set at P <.05. RESULTS: The mean age in the ARB cohort was 61.8 years (standard deviation [SD] = 10.0), whereas in the control cohort, it was 54.8 years (SD = 12.3) (P < .001). The ARB cohort had significantly lower rates of newly diagnosed adhesive capsulitis compared with the control cohort at both 1 year (0.15% vs. 0.55%, P < .001) and 2 years (0.3% vs. 0.78%, P < .001). Similar findings were observed for the arthroscopic capsular release/MUA cohort associated with adhesive capsulitis. After adjusting for confounding factors, the lower rates of adhesive capsulitis and arthroscopic capsular release/MUA associated with adhesive capsulitis in the ARB cohort remained statistically significant (P < .001). CONCLUSION: Patients prescribed ARBs experienced a decreased rate of newly diagnosed adhesive capsulitis, as well as adhesive capsulitis requiring surgical intervention when compared to a control cohort. These findings suggest a potential protective effect of ARBs against the development of adhesive capsulitis. Further investigations are warranted to elucidate the underlying mechanisms and establish a causal relationship.

Optimizing Safe Opioid Prescribing: A Paradigm Shift in Buprenorphine Management for Orthopaedic Surgery.

The worsening opioid epidemic in the United States, exacerbated by the COVID-19 pandemic, necessitates innovative approaches to pain management. Buprenorphine, a long-acting opioid, has gained popularity due to its safety profile and accessibility. Orthopaedic surgeons, encountering an increasing number of patients on buprenorphine, face challenges in perioperative management. This article will update orthopaedic surgeons on new developments in the understanding of buprenorphine as a pain reliever and share evidence-based practice guidelines for buprenorphine management. For patients on buprenorphine for opioid use disorder or chronic pain, the updated recommendation is to continue their home dose of buprenorphine through the perioperative period. The patient's buprenorphine prescriber should be contacted and notified of any impending surgery. The continuation of buprenorphine should be accompanied by a multimodal approach to analgesia, including a preoperative discussion about expectations of pain and pain control, regional anesthesia, standing acetaminophen, Nonsteroidal anti-inflammatory drugs when possible, gabapentinoids at night for patients under 65 years, cryotherapy, elevation, and early mobilization. Patients can also be prescribed short-acting, immediate-release opioids for breakthrough pain. Transdermal buprenorphine is emerging as an excellent option for the management of acute perioperative pain in both elective and nonelective orthopaedic patients. A single patch can provide a steady dose of pain medication for up to 1 week during the postoperative period. A patch delivery method can help combat patient nonadherence and ultimately provide better overall pain control. In the future, transdermal buprenorphine patches could be applied in virtually all fracture surgery, spinal surgery, total joint arthroplasty, ligament reconstructions with bony drilling, etc. As the stigma surrounding buprenorphine decreases, further opportunities for perioperative use may develop.

Postoperative Angiotensin Receptor Blocker Use is Associated With Decreased Rates of Manipulation Under Anesthesia, Arthroscopic Lysis of Adhesions, and Prosthesis-Related Complications in Patients Undergoing Total Knee Arthroplasty.

BACKGROUND: The cellular mechanisms underlying excess scar tissue formation in arthrofibrosis following total knee arthroplasty (TKA) are well-described. Angiotensin receptor blockers (ARB), particularly losartan, is a commonly prescribed antihypertensive with demonstrated antifibrotic properties. This retrospective study aimed to assess the rates of 1- and 2-year postoperative complications in patients who filled prescriptions for ARBs during the 90 days after TKA. METHODS: Patients undergoing primary TKA were selected from a large national insurance database, and the impact of ARB use after TKA on complications was assessed. Of the 1,299,106 patients who underwent TKA, 82,065 had filled at least a 90-day prescription of losartan, valsartan, or olmesartan immediately following their TKA. The rates of manipulation under anesthesia (MUA), arthroscopic lysis of adhesions (LOA), aseptic loosening, periprosthetic fracture, and revision at 1 and 2 years following TKA were analyzed using multivariable logistic regressions to control for various comorbidities. RESULTS: ARB use was associated with decreased rates of MUA (odds ratio [OR] = 0.94, 95% confidence interval (CI), 0.90 to 0.99), arthroscopy/LOA (OR = 0.86, 95% CI, 0.77 to 0.95), aseptic loosening (OR = 0.71, 95% CI, 0.61 to 0.83), periprosthetic fracture (OR = 0.58, 95% CI, 0.46 to 0.71), and revision (OR = 0.79, 95% CI, 0.74 to 0.85) 2 years after TKA. CONCLUSIONS: ARB use throughout the 90 days after TKA is associated with a decreased risk of MUA, arthroscopy/LOA, aseptic loosening, periprosthetic fracture, and revision, demonstrating the potential protective abilities of ARBs. Prospective studies evaluating the use of ARBs in patients at risk for postoperative stiffness would be beneficial to further elucidate this association.

Application of a CRISPR Sequence-Based Method for a Large-Scale Assessment of Salmonella Serovars in Ontario Poultry Production Environments.

Accurate detection of all Salmonella serovars present in a sample is important in surveillance programs. Current detection protocols are limited to detection of a predominant serovar, missing identification of less abundant serovars in a sample. An alternative method, called CRISPR-SeroSeq, serotyping by sequencing of amplified CRISPR spacers, was employed to detect multiple serovars in a sample without the need of culture isolation. The CRISPR-SeroSeq method successfully detected 34 most frequently reported Salmonella serovars in pure cultures and target serovars at 104 CFU/mL in 27 Salmonella-negative environmental enrichment samples post-spiked with one of 15 different serovars, plus 2 additional serovars at 1 log CFU/mL higher abundance. When the method was applied to 442 naturally contaminated environmental samples collected from 192 poultry farms, 25 different serovars were detected from 430 of the samples. In 73.1% of the samples, 2 to 7 serovars were detected, with Salmonella Kiambu (55.7%), Salmonella Infantis (48.4%), Salmonella Kentucky (27.1%), Salmonella Livingstone (26.6%), and Salmonella Mbandaka/Montevideo (23.4%) being the most prevalent on the farms. Single isolates from 384 samples were also analyzed using a traditional serotyping method, and the same serovar identified by culture was detected by CRISPR-SeroSeq in 96.1% (369/384) of samples, with the former missing detection of additional and sometimes critical serovars. The surveillance data obtained via CRISPR-SeroSeq revealed a significant emergence of Salmonella Kiambu and Salmonella Rissen on poultry farms in Ontario. The results highlight the effectiveness of the CRISPR-SeroSeq approach in detecting multiple Salmonella serovars in poultry environmental samples under applied conditions, providing updated surveillance information on Salmonella serovars on poultry farms in Ontario. IMPORTANCE The CRISPR-SeroSeq method represents an alternative molecular tool to the traditional culture-based serotyping method that can detect multiple Salmonella serovars in a sample and provide rapid serovar results without the need of selective enrichment and culture isolation. The evaluation results can facilitate implementation of the method in routine Salmonella surveillance on poultry farms and in outbreak investigations. The application of the method can increase the accuracy of current serovar prevalence information. The results highlight the effectiveness of the validated method and the need for monitoring Salmonella serovars in poultry environments to improve current surveillance programs. The updated surveillance data provide timely information on emergence of different Salmonella serovars on poultry farms in Ontario and support on-farm risk assessment and risk management of Salmonella.

First-in-class humanized FSH blocking antibody targets bone and fat.

Blocking the action of FSH genetically or pharmacologically in mice reduces body fat, lowers serum cholesterol, and increases bone mass, making an anti-FSH agent a potential therapeutic for three global epidemics: obesity, osteoporosis, and hypercholesterolemia. Here, we report the generation, structure, and function of a first-in-class, fully humanized, epitope-specific FSH blocking antibody with a KD of 7 nM. Protein thermal shift, molecular dynamics, and fine mapping of the FSH-FSH receptor interface confirm stable binding of the Fab domain to two of five receptor-interacting residues of the FSHß subunit, which is sufficient to block its interaction with the FSH receptor. In doing so, the humanized antibody profoundly inhibited FSH action in cell-based assays, a prelude to further preclinical and clinical testing.

A Diagnosis of Vitamin D Deficiency Is Associated With Increased Rates of Anterior Cruciate Ligament Tears and Reconstruction Failure.

PURPOSE: To characterize the association between a diagnosis of hypovitaminosis D and primary anterior cruciate ligament (ACL) tear, primary anterior cruciate ligament reconstruction (ACLR), and revision ACLR in different sex and age cohorts. METHODS: In this retrospective cohort study of the PearlDiver claims database, records were queried between January 1, 2011, and October 31, 2018 for all patients aged 10 to 59 years who received a diagnosis of hypovitaminosis D. Rates of primary ACL tears, primary reconstruction, and revision reconstruction were calculated for sex- and age-specific cohorts and compared with a control of patients without a diagnosis of hypovitaminosis D. Incidence rates for primary ACL injuries were calculated, and multivariable logistic regression was used to compare rates of ACL injury, primary reconstruction, and revision reconstruction while controlling for age, sex, Charlson Comorbidity Index, and several other comorbidities. RESULTS: Among the 328,011 patients (mean age 41.9 ± 12.6 years, 65.8% female) included in both the hypovitaminosis D and control cohorts, the incidence of ACL tears was 115.2 per 100,000 person-years (95% confidence interval [CI] 107.2-123.7) compared with 61.0 (95% CI 55.2-67.2) in the demographic- and comorbidity-matched control cohort. The study cohort was significantly more likely to suffer an ACL tear over a 1- (aOR 1.67, 95% CI 1.41-1.99, P < .001) and 2-year (aOR 1.81, 95% CI 1.59-2.06, P < .001) period. This trend remained for both male patients at the 1- (aOR 1.66, 95% CI 1.29-2.14, P < .001) and 2-year (aOR 1.68, 95% CI 1.37-2.06, P < .001) mark and female patients at the 1- (aOR 1.69, 95% CI 1.33-2.14, P < .001) and 2-year (aOR 1.80, 95% CI 1.51-2.14, P < .001) mark. Finally, patients with vitamin D deficiency had a significantly increased likelihood of undergoing a revision ACLR within 2 years of a primary reconstruction (aOR 1.28, 95% CI 1.05-1.55, P = .012). CONCLUSIONS: This study reports an association between patients previously diagnosed with hypovitaminosis D and significantly increased rates of both index ACL tears (81% increase within 2 years of diagnosis) and revision ACLR (28% within 2 years). These results identify a population with increased odds of injury and provide valuable knowledge as we expand our understanding of the relationship between vitamin D and musculoskeletal health. LEVEL OF EVIDENCE: Level III, retrospective database study.

Increased Medical and Implant-Related Complications in Total Hip Arthroplasty Patients With Underlying Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been associated with impaired bone metabolism. The purpose of this study is to investigate rates of readmission, respiratory complications, implant-related complications, and revision after total hip arthroplasty (THA) in patients with and without underlying COPD. METHODS: The PearlDiver Mariners database was used to divide patients undergoing primary THA (CPT-27130) into two cohorts: 1) THA with COPD (including asthma) or 2) THA without COPD. The incidence of 30-day readmission, COPD exacerbation, pneumonia, other respiratory complications as well as dislocations, mechanical loosening, and joint prosthetic infection was calculated through logistic regression. The risk of THA revision was also assessed through Cox-proportional hazards regression. All regression controlled for age, gender, and medical comorbidities found to be associated with COPD. RESULTS: Between 2010 and 2018, 97,784 THA patients with COPD and 338,243 THA patient without COPD were studied. THA patients with COPD had higher risk of 30-day readmission (aOR = 1.17, 95% CI 1.11-1.23, P < .0001). There was higher risk of 30-day pneumonia (aOR = 2.07, 95% CI 1.76-2.44, P < .0001). THA patients with COPD also faced higher risk of 30-day dislocations (aOR = 1.31, 95% CI 1.19-1.45, P < .0001), joint prosthetic infections (aOR = 1.25, 95% CI 1.14-1.37, P < .0001), and periprosthetic fracture (aOR = 1.19, 95% CI 1.07-1.32, P = .0015). Regarding revisions, 3.3% of THA patients with COPD underwent THA revision at 1 year, a higher risk than THA patients without COPD (aOR = 1.11, 95% CI 1.06-1.16, P < .0001). CONCLUSION: Patients undergoing THA with underlying COPD face a higher rate of comorbidities, respiratory complications, implant complications, and revision surgeries, than patients without COPD. LEVEL OF EVIDENCE: III.

Human GDPD3 overexpression promotes liver steatosis by increasing lysophosphatidic acid production and fatty acid uptake.

The glycerol phosphate pathway produces more than 90% of the liver triacylglycerol (TAG). LysoPA, an intermediate in this pathway, is produced by glycerol-3-phosphate acyltransferase. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), whose gene was recently cloned, contains lysophospholipase D activity, which produces LysoPA from lysophospholipids. Whether human GDPD3 plays a role in hepatic TAG homeostasis is unknown. We hypothesized that human GDPD3 increases LysoPA production and availability in the glycerol phosphate pathway, promoting TAG biosynthesis. To test our hypothesis, we infected C57BL/6J mice with adeno-associated virus encoding a hepatocyte-specific albumin promoter that drives GFP (control) or FLAG-tagged human GDPD3 overexpression and fed the mice chow or a Western diet to induce hepatosteatosis. Hepatic human GDPD3 overexpression induced LysoPA production and increased FA uptake and incorporation into TAG in mouse hepatocytes and livers, ultimately exacerbating Western diet-induced liver steatosis. Our results also showed that individuals with hepatic steatosis have increased GDPD3 mRNA levels compared with individuals without steatosis. Collectively, these findings indicate that upregulation of GDPD3 expression may play a key role in hepatic TAG accumulation and may represent a molecular target for managing hepatic steatosis.

Putaminal Diffusion Restriction in a Case of Methanol Toxicity with Clinical Recovery.

A 32-year-old male presented to the emergency department for confusion, dyspnea, and a "white out" of his central vision over the preceding 24 hours. The patient had recently consumed a bottle of alcohol purchased overseas. Bloodwork revealed a severe metabolic acidosis (pH 6.90) and a critically high methanol level of 28.9 mmol/l. Shortly after presentation, the patient went into respiratory failure and became comatose. He was intubated and admitted to the ICU.

A stakeholder meeting exploring the ethical perspectives of immediately sequential bilateral cataract surgery.

PURPOSE: The purported benefits and risks of immediately sequential bilateral cataract surgery (ISBCS) have been well described, yet the procedure remains controversial among UK ophthalmologists. As many of the controversies of ISBCS are underpinned by ethical dilemmas, the aim of this work was to explore the ethical perspectives of ISBCS from a variety of stakeholder viewpoints. METHOD: A semi-structured independent stakeholder meeting was convened at the Royal College of Ophthalmologists London headquarters in June 2018. In total, 29 stakeholders attended the meeting. The professional characteristics of stakeholders included but were not limited to: ophthalmologists (9), patients (5), religious leaders (4), ethicists (2), lawyers (2) and commissioners (1). Thematic qualitative analysis using methodology proposed by Braun and Clarke was conducted on the resultant transcript of the discussion. RESULTS: Themes identified include: (1) beneficence and non-maleficence (patient benefits, patient risks, the uncertainties of risk, patient interpretation of the risk-benefit analysis); (2) autonomy (informed consent, the barriers to communication); (3) distributive justice (the allocation of resources: the individual vs the collective). CONCLUSION: This analysis provides a reference point for the ethical factors surrounding ISBCS. The stakeholders concluded that this approach was an ethical undertaking provided patient autonomy was appropriately attained. This requires a patient's interpretation of the risk-benefit balance, which must include an understanding of the low but unquantifiable risk of severe complications. A surgeon must aim to minimise risks through the adaption of accepted surgical protocols and by performing appropriate patient selection. Currently, cost savings to healthcare that may occur following the implementation of ISBCS should be considered a secondary benefit of the protocol.

Advanced Digital Health Technologies for COVID-19 and Future Emergencies.

Background: Coronavirus disease 2019 (COVID-19) has led to a national health care emergency in the United States and exposed resource shortages, particularly of health care providers trained to provide critical or intensive care. This article describes how digital health technologies are being or could be used for COVID-19 mitigation. It then proposes the National Emergency Tele-Critical Care Network (NETCCN), which would combine digital health technologies to address this and future crises. Methods: Subject matter experts from the Society of Critical Care Medicine and the Telemedicine and Advanced Technology Research Center examined the peer-reviewed literature and science/technology news to see what digital health technologies have already been or could be implemented to (1) support patients while limiting COVID-19 transmission, (2) increase health care providers' capability and capacity, and (3) predict/prevent future outbreaks. Results: Major technologies identified included telemedicine and mobile care (for COVID-19 as well as routine care), tiered telementoring, telecritical care, robotics, and artificial intelligence for monitoring. Several of these could be assimilated to form an interoperable scalable NETCCN. NETCCN would assist health care providers, wherever they are located, by obtaining real-time patient and supplies data and disseminating critical care expertise. NETCCN capabilities should be maintained between disasters and regularly tested to ensure continual readiness. Conclusions: COVID-19 has demonstrated the impact of a large-scale health emergency on the existing infrastructures. Short term, an approach to meeting this challenge is to adopt existing digital health technologies. Long term, developing a NETCCN may ensure that the necessary ecosystem is available to respond to future emergencies.

Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure.

Hepatic encephalopathy is a serious neurological complication of liver failure. Serum bile acids are elevated after liver damage and may disrupt the blood-brain barrier and enter the brain. Our aim was to assess the role of serum bile acids in the neurological complications after acute liver failure. C57Bl/6 or cytochrome p450 7A1 knockout (Cyp7A1(-/-)) mice were fed a control, cholestyramine-containing, or bile acid-containing diet before azoxymethane (AOM)-induced acute liver failure. In parallel, mice were given an intracerebroventricular infusion of farnesoid X receptor (FXR) Vivo-morpholino before AOM injection. Liver damage, neurological decline, and molecular analyses of bile acid signaling were performed. Total bile acid levels were increased in the cortex of AOM-treated mice. Reducing serum bile acids via cholestyramine feeding or using Cyp7A1(-/-) mice reduced bile acid levels and delayed AOM-induced neurological decline, whereas cholic acid or deoxycholic acid feeding worsened AOM-induced neurological decline. The expression of bile acid signaling machinery apical sodium-dependent bile acid transporter, FXR, and small heterodimer partner increased in the frontal cortex, and blocking FXR signaling delayed AOM-induced neurological decline. In conclusion, circulating bile acids may play a pathological role during hepatic encephalopathy, although precisely how they dysregulate normal brain function is unknown. Strategies to minimize serum bile acid concentrations may reduce the severity of neurological complications associated with liver failure.