FDC:TFH Interactions within Cervical Lymph Nodes of SIV-Infected Rhesus Macaques

Cerebrospinal fluid (CSF) drains via the lymphatic drainage pathway. This lymphatic pathway connects the central nervous system (CNS) to the cervical lymph node (CLN). As the CSF drains to CLN via the dural and nasal lymphatics, T cells and antigen presenting cells pass along the channels from the subarachnoid space through the cribriform plate. Human immunodeficiency virus (HIV) may also egress from the CNS along this pathway. As a result, HIV egressing from the CNS may accumulate within the CLN. Towards this objective, we analyzed CLNs isolated from rhesus macaques that were chronically-infected with simian immunodeficiency virus (SIV). We detected significant accumulation of SIV within the CLNs. SIV virion trapping was observed on follicular dendritic cells (FDCs) localized within the follicular regions of CLNs. In addition, SIV antigens formed immune complexes when FDCs interacted with B cells within the germinal centers. Subsequent interaction of these B cells with CD4+ T follicular helper cells (T_FHs) resulted in infection of the latter. Of note, 73% to 90% of the T_FHs cells within CLNs were positive for SIV p27 antigen. As such, it appears that not only do the FDCs retain SIV they also transmit them (via B cells) to T_FHs within these CLNs. This interaction results in infection of T_FHs in the CLNs. Based on these observations, we infer that FDCs within the CLNs have a novel role in SIV entrapment with implications for viral trafficking.     

Distance traveled to undergo revision shoulder arthroplasty is impacted by patient demographics and exceeds that of primary shoulder arthroplasty

BackgroundPrevious research has highlighted disparities in access to and outcomes following shoulder arthroplasty. The purpose of this study is to compare travel distance for primary vs. revision surgery and to determine the relationships between travel distance to undergo revision shoulder arthroplasty and patient demographics and postoperative adverse outcomes. We hypothesized that older patients, those with increased medical comorbidities, and those with greater financial resources would travel farther for surgery.MethodsThe Healthcare Cost and Utilization Project, American Hospital Association, and UnitedStatesZipCodes.org Enterprise data sets were compiled to collect data on patient demographics, operation performed, and postoperative adverse outcomes. Population-weighted zip code centroid points of patients’ residences as well as hospital coordinates were used to approximate the distance traveled to undergo shoulder arthroplasty. Kruskal-Wallis tests and logistic regression analyses were used to analyze the relationship between travel distance and patients’ demographics and postoperative outcomes.ResultsPatients traveled farther to undergo revision shoulder arthroplasty than to undergo primary shoulder arthroplasty (P = .0001). Among patients who underwent revision operations, older age (P = .0001) and increased medical comorbidities (P = .003) were associated with decreased travel distance. White patients and those with commercial insurance traveled farther to receive care (P = .0001). There were no clinically significant associations between postoperative outcomes following revision surgery and travel distance.ConclusionPatients may travel farther to undergo revision surgery owing to patient preferences or because these complex operations are performed at fewer centers. Younger and healthier patients, white patients, and those with commercial insurance plans traveled farther to receive care. Future work is needed to determine the underlying causes of these disparities and whether it is patient preferences or systemic factors such as hospital density or access to high-quality health insurance that are influencing access to this specialized surgical care.     

MRI-Based Shoulder Osteoarthritis Severity score (SOAS) is predictive of functional improvement following total shoulder arthroplasty

BackgroundTotal shoulder arthroplasty (TSA) is an increasingly common treatment for end-stage glenohumeral osteoarthritis. Current established radiographic measures and classification systems do not predict patient-reported outcomes from TSA. We hypothesized that the MRI-based Shoulder Osteoarthritis Severity (SOAS) Score would correlate with subjective improvement following TSA.MethodsPatients undergoing TSA with preoperative shoulder MRIs and pre- and postoperative ASES scores with minimum 2-year follow-up were included from a prospectively collected institutional shoulder arthroplasty database. SOAS scores, which is measured from 0 to 100 with an increasing score reflecting greater global degenerative changes, were assessed by two independent reviewers, and Samilson-Prieto grade and Walch classification were scored by one reviewer. Average SOAS scores were correlated with demographic factors and pre-, post-, and change (Δ) in ASES scores. Statistical analysis was performed with STATA with Pearson's correlation, one-way ANOVA, and ROC analysis, with significance defined by p <.05.Results30 patients (age 63 ± 10 years, 14 females, 16 males) who underwent primary anatomic TSA were included. The intraclass correlation coefficient (ICC) for total SOAS scores calculated by reviewers was 0.91. SOAS score correlated significantly with ΔASES (r = 0.61, p = .0003) and preoperative ASES (r = -0.37, p = .042), with greater MRI-based degenerative change associated with greater improvement after TSA and lower preoperative ASES score. No significant relationship was found between either Samilson-Prieto or Walch classification and SOAS or ASES scores. No significant relationship was found between SOAS scores and age, sex, or BMI. Using an MCID of 21 as previously reported, an ROC curve was generated and found to have an AUC of 0.96. A SOAS score cut-point of 36.25 was found to maximize sensitivity and specificity in predicting reaching MCID.ConclusionWe observed a significant positive correlation between the MRI-based SOAS score and functional improvement following TSA measured using change in ASES scores, indicating that patients with more advanced degenerative changes on MRI had greater improvement after shoulder replacement surgery. We found that the correlation strength was highest when comparing total SOAS score to ΔASES as opposed to any individual sub-component of the SOAS score. The MRI-based SOAS score for shoulder osteoarthritis may be a valuable tool for predicting patient outcomes following TSA.Level of evidenceLevel III; Retrospective Cohort Comparison; Prognosis Study     

Failed prior rotator cuff repair is associated with worse clinical outcomes after reverse total shoulder arthroplasty

BackgroundThe purpose of this study is to determine the comparative risk profile and clinical outcomes for patients undergoing reverse total shoulder arthroplasty (RTSA) for cuff tear arthropathy (CTA) without failed prior rotator cuff repair (RCR) compared with RTSA for CTA with prior RCR.MethodsFrom 2006 to 2014, all patients who underwent RTSA by two surgeons after failed RCR with minimum 2-year follow-up were identified. Patients who underwent RTSA with failed prior RCR were matched in a 1:1 ratio to patients undergoing primary RTSA, while controlling for demographic factors, prosthesis design, and surgeon. Postoperative active forward elevation and active external rotation were recorded. Outcome measures included American Shoulder and Elbow Surgeons score, Visual Analog Scale (VAS), and Simple Shoulder Test. Perioperative complications and rates of secondary reoperation were noted, and comparative multivariate analysis was performed.ResultsOf 262 patients, 192 (73.3%) were available at minimum 2-year follow-up. The prior RCR group had a significantly higher complication rate (17.4%, n = 15) than the primary RTSA group (3.8%, n = 4) (P = .001), although no significant difference in periprosthetic infection (P = .469) or secondary revision rate (P = .136) was observed. At mean 36.3 ± 26.1-month follow-up, the prior RCR group had statistically worse American Shoulder and Elbow Surgeons score (P < .001), VAS (P = .001), Simple Shoulder Test (P < .001), and active forward elevation (P = .006). Patients with multiple failed RCR attempts (n = 38) before RTSA demonstrated no significant differences versus isolated failed RCR (n = 48; P > .05).ConclusionThis study demonstrated that patients with RTSA after prior failed RCR have significantly worse patient-reported outcomes and greater rate of perioperative complications than patients undergoing primary RTSA for CTA.     

Factors influencing lower extremity amputation outcomes in people with active foot ulceration in regional Australia: A retrospective cohort study

Australia has the second highest rate of non-traumatic lower extremity amputation (LEA) globally. Australia's large geographical size is one of the biggest challenges facing limb preservation services and may be contributing to LEA. The aim of this study was to determine what factors contribute to the likelihood of LEA in people with active foot ulceration in regional Australia. This retrospective cohort study audited patients with active foot ulceration in a multidisciplinary high risk foot service (HRFS) in regional Australia. Neurological, vascular and wound characteristics were systematically extracted, along with demographic information. Participants were followed for at least 12 months until healing or LEA occurred. Correlations between LEA and clinical and demographic characteristics were assessed using the Pearson's product moment correlation coefficient and chi squared test for independence. Significant variables (p < 0.05) were included in the model. Direct logistic regression assessed the independent contribution of significantly correlated variables on the likelihood of LEA. Of note, 1876 records were hand screened with 476 participants (25%) meeting the inclusion criteria. Geographical distance from the HRFS, toe systolic pressure (TSP), diabetes and infection were all significantly correlated with LEA and included in the logistic regression model. TSP decrease of 1 mmHg (OR 1.02, 95% CI 1.01–1.03), increased geographical distance (1 km) from HRFS (OR 1.006, 95% CI 1.001–1.01) infection (OR 2.08, 95% CI 1.06–4.07) and presence of diabetes (OR 3.77, 95% CI 1.12–12.65) were all significantly associated with increased likelihood of LEA. HRFS should account for the disparity in outcomes between patients living in close proximity to their service, compared to those in rural areas. Optimal management of diabetes, vascular perfusion and control of infection may also contribute to preventing LEA in people with active foot ulceration.     

An OxPLORE Initiative Evaluating Children’s Surgery Resources Worldwide: A Cross-sectional Implementation of the OReCS Document

World Journal of Surgery - The Global Initiative for Children's Surgery (GICS) group produced the Optimal Resources for Children’s Surgery (OReCS) document in 2019, listing standards of...     

Mechanism of action of Melaleuca alternifolia (tea tree) oil on Staphylococcus aureus determined by time-kill,lysis, leakage,and salt tolerance assays and electron microscopy

The essential oil of Melaleuca alternifolia (tea tree) has broad-spectrum antimicrobial activity. The mechanisms of action of tea tree oil and three of its components, 1,8-cineole, terpinen-4-ol, and alpha-terpineol, against Staphylococcus aureus ATCC 9144 were investigated. Treatment with these agents at their MICs and two times their MICs, particularly treatment with terpinen-4-ol and alpha-terpineol, reduced the viability of S. aureus. None of the agents caused lysis, as determined by measurement of the optical density at 620 nm, although cells became disproportionately sensitive to subsequent autolysis. Loss of 260-nm-absorbing material occurred after treatment with concentrations equivalent to the MIC, particularly after treatment with 1,8-cineole and alpha-terpineol. S. aureus organisms treated with tea tree oil or its components at the MIC or two times the MIC showed a significant loss of tolerance to NaCl. When the agents were tested at one-half the MIC, only 1,8-cineole significantly reduced the tolerance of S. aureus to NaCl. Electron microscopy of terpinen-4-ol-treated cells showed the formation of mesosomes and the loss of cytoplasmic contents. The predisposition to lysis, the loss of 260-nm-absorbing material, the loss of tolerance to NaCl, and the altered morphology seen by electron microscopy all suggest that tea tree oil and its components compromise the cytoplasmic membrane.     

Self‐rated preparedness of Australian prevocational hospital doctors for emergencies

Objective: To determine perceived preparedness of Australian hospital‐based prevocational doctors for resuscitation skills and management of emergencies, and to identify differences between doctors who perceive themselves well prepared and those who perceive themselves poorly prepared for emergencies, in demographics and exposure to desired learning methods. Methods: Questionnaire consisting of a mix of graded Likert scales and free‐text answers distributed to 36 Australian hospitals for secondary distribution to hospital medical officers. Results: From 2607 questionnaires posted, 470 (18.1%) were returned. Thirty‐one per cent (95% confidence interval [CI] 26–35%) felt well prepared for resuscitation and management of emergencies, 41% (CI 37–45%) felt adequately prepared and 28% (CI 24–32%) felt they were not well prepared. Those who felt well prepared reported that they had experienced more exposure to a range of educational methods, including consultant contact, supervisor feedback, clinical skills, high fidelity simulator sessions and unit meetings. Well‐prepared and poorly prepared doctors had similar opinions of the usefulness of various learning methods, but the poorly prepared group more frequently expressed a desire for increased exposure to contact with registrars and consultants, clinical skills sessions and hospital and unit meetings. There were no differences in gender, age or country of origin (Australia vs international medical graduates) between those who felt well or poorly prepared. Conclusions: Many prevocational hospital doctors feel inadequately prepared for the management of emergencies. Perceived preparedness is associated with more exposure to particular educational activities. Increasing exposure to learning of emergencies in undergraduate and prevocational years could reduce the number of junior doctors who feel poorly prepared for emergencies.     

Estimating the potential pool of uncontrolled DCD donors in the United States

Organs from uncontrolled DCD donors (uDCDs) have expanded donation in Europe since the 1980s, but are seldom used in the United States. Cited barriers include lack of knowledge about the potential donor pool, lack of robust outcomes data, lack of standard donor eligibility criteria and preservation methods, and logistical and ethical challenges. To determine whether it would be appropriate to invest in addressing these barriers and building this practice, we sought to enumerate the potential pool of uDCD donors. Using data from the Nationwide Emergency Department Sample, the largest all‐payer emergency department (ED) database, between 2013 and 2016, we identified patients who had refractory cardiac arrest in the ED. We excluded patients with contraindications to both deceased donation (including infection, malignancy, cardiopulmonary disease) and uDCD (including hemorrhage, major polytrauma, burns, and poisoning). We identified 9828 (range: 9454‐10 202) potential uDCDs/y; average age was 32 years, and all were free of major comorbidity. Of these, 91.1% had traumatic deaths, with major causes including nonhead blunt injuries (43.2%) and head injuries (40.1%). In the current era, uDCD donors represent a significant potential source of unused organs. Efforts to address barriers to uDCD in the United States should be encouraged.