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Timothy G Murray,1,2 Andrew J Layton,3 Kuo B Tong,3 Michael Gittelman,2 Azeema Latiff,1,2 Daniel Gologorsky,2 Michael M Vigoda21Murray Ocular Oncology and Retina, Miami, FL, USA; 2Bascom Palmer Eye Institute, Anne Bates Leach Eye Hospital, Departments of Ophthalmology, Anesthesiology and Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, USA; 3Quorum Consulting, San Francisco, CA, USABackground: Microincisional vitrectomy surgery (MIVS) is the current standard surgical approach for pars plana vitrectomy. Historically, the most common surgical platform for vitrectomy surgery, since its introduction in 1997, has been the Accurus vitrectomy system. Recent introduction of the next generation of vitrectomy platforms has generated concerns associated with transitioning to new technology in the operating room environment. This study compared, in a matched fashion, surgical use of the Accurus vitrectomy system and the next generation Constellation Vision System to evaluate surgical efficiencies, complications, and user perceptions of this transition.Methods: Electronic health records were abstracted as a hospital quality assurance activity and included all vitreoretinal surgical procedures at the Bascom Palmer Eye Institute, Anne Bates Leach Eye Hospital, during two discrete 12-month time periods. These two periods reflected dedicated usage of the Accurus (June 2008–May 2009) and Constellation Vision (July 2009–June 2010) systems. Data were limited to a single surgeon and evaluated for operating room (OR) total time usage/day, OR case time/case, and OR surgical time/case. Further analysis evaluated all patients undergoing combined MIVS and clear cornea phacoemulsification/intraocular lens (IOL) implantation during each individual time period to determine the impact of the instrumentation on these parameters. All records were evaluated for intraoperative complications.Results: Five hundred and fourteen eligible patients underwent MIVS during the 2-year study windows, with 281 patients undergoing surgery with the Accurus system and 233 patients undergoing surgery with the Constellation system. Combined MIVS and phacoemulsification with IOL implantation was performed 141 times during this period with the Accurus and 158 times during the second study period with the Constellation. Total number of patients operated per day increased from 7.55 with Accurus to 8.53 with Constellation. Surgical room time decreased from 56 minutes with Accurus to 52 minutes with Constellation, and procedure time decreased from 35 minutes with Accurus to 31 minutes with Constellation (P < 0.004). Combined MIVS/phacoemulsification surgery saw similar declines in surgical room time and procedure time (P < 0.001). Subset analysis of procedures limited by case number per day (eg, four cases/day, five cases/day, six cases/day, and seven or more cases/day) showed similar outcomes with a decrease in surgical room time and procedure time. No increases in surgery-related complications were noted by quality assurance review during these time periods.Discussion: Transitioning to advanced surgical technology is a complex issue for the surgeon, the hospital team, and the hospital administration. This study documents improvement in three significant measures of surgical efficiency: operative number of patients per day, operative room time, and surgical procedure time that reflect the positive impact of the novel, combined, integrated, posterior and anterior, ophthalmologic surgical platform of the Constellation Vision System. These data are imperative to evaluate the impact of transition from one surgical platform to another. During this transition, hospital quality assurance review and surgeon evaluation of operative complications showed no increased concerns for the shift from the Accurus to the Constellation Vision System surgical platform. Further, both operative staff and surgeons felt that the transition to the Constellation was not associated with increases in difficulty with setup, turnover, or use and that the Constellation decreased safety concerns for surgical usage. Ultimately, in this case, new technology benefited the surgeon, the patient, and the hospital.Keywords: MIVS, vitrectomy, new technology

Mycobacterial glycolipids are important cell envelope structures that drive host-pathogen interactions. Arguably, the most important are lipoarabinomannan (LAM) and its precursor, lipomannan (LM), which are trafficked from the bacterium to the host via unknown mechanisms. Arabinomannan is thought to be a capsular derivative of these molecules, lacking a lipid anchor. However, the mechanism by which this material is generated has yet to be elucidated. Here, we describe the identification of a glycoside hydrolase family 76 enzyme that we term LamH (Rv0365c in Mycobacterium tuberculosis) which specifically cleaves α-1,6-mannoside linkages within LM and LAM, driving its export to the capsule releasing its phosphatidyl-myo-inositol mannoside lipid anchor. Unexpectedly, we found that the catalytic activity of this enzyme is important for efficient exit from stationary phase cultures, potentially implicating arabinomannan as a signal for growth phase transition. Finally, we demonstrate that LamH is important for M. tuberculosis survival in macrophages., (© 2024. The Author(s).)

Mycobacterial glycolipids are important cell envelope structures that drive host-pathogen interactions. Arguably, the most important amongst these are lipoarabinomannan (LAM) and its precursor, lipomannan (LM), which are both trafficked out of the bacterium to the host via unknown mechanisms. An important class of exported LM/LAM is the capsular derivative of these molecules which is devoid of its lipid anchor. Here, we describe the identification of a glycoside hydrolase family 76 enzyme that we term LamH which specifically cleaves α-1,6-mannoside linkages within LM and LAM, driving its export to the capsule releasing its phosphatidyl- myo -inositol mannoside lipid anchor. Unexpectedly, we found that the catalytic activity of this enzyme is important for efficient exit from stationary phase cultures where arabinomannan acts as a signal for growth phase transition. Finally, we demonstrate that LamH is important for Mycobacterium tuberculosis survival in macrophages. These data provide a new framework for understanding the biological role of LAM in mycobacteria.

Bacterial cell growth and division require the coordinated action of enzymes that synthesize and degrade cell wall polymers. Here, we identify enzymes that cleave the D-arabinan core of arabinogalactan, an unusual component of the cell wall of Mycobacterium tuberculosis and other mycobacteria. We screened 14 human gut-derived Bacteroidetes for arabinogalactan-degrading activities and identified four families of glycoside hydrolases with activity against the D-arabinan or D-galactan components of arabinogalactan. Using one of these isolates with exo-D-galactofuranosidase activity, we generated enriched D-arabinan and used it to identify a strain of Dysgonomonas gadei as a D-arabinan degrader. This enabled the discovery of endo- and exo-acting enzymes that cleave D-arabinan, including members of the DUF2961 family (GH172) and a family of glycoside hydrolases (DUF4185/GH183) that display endo-D-arabinofuranase activity and are conserved in mycobacteria and other microbes. Mycobacterial genomes encode two conserved endo-D-arabinanases with different preferences for the D-arabinan-containing cell wall components arabinogalactan and lipoarabinomannan, suggesting they are important for cell wall modification and/or degradation. The discovery of these enzymes will support future studies into the structure and function of the mycobacterial cell wall., (© 2023. The Author(s).)

Introduction: First-line targeted therapies have been developed for advanced non-small-cell lung cancer (NSCLC). However, small biopsy samples pose a challenge to testing all relevant biomarkers. The present study characterized clinician-ordered single-gene lung cancer testing and evaluated tissue stewardship and the ability to successfully determine mutation status with single-gene testing or investigational use of the Oncomine Dx Target Test., Materials and Methods: Clinician-submitted orders for 3659 single-gene tests (EGFR, ALK, ROS1, BRAF, KRAS, ERBB2, MET, RET, FGFR1) across 1402 samples at a large US-based commercial reference laboratory and 169 investigational Oncomine Dx Target Tests were retrospectively evaluated. The testing success rates and tissue consumption were evaluated by sample type, test type, and number of single-gene tests per sample., Results: The large majority of lung tissue samples submitted for clinical testing were small (70.5% core needle biopsies; 10.0% fine needle aspirations). With single-gene testing, mutation status was successfully reported for ≥ 1 biomarker for 88.4% of the clinical samples. The success rates decreased and tissue consumption increased with testing of additional biomarkers. Investigational Oncomine Dx Target Tests were permitted 1 tissue slide each and demonstrated success rates similar to single-gene testing for ≥ 5 biomarkers on core needle biopsies, ≥ 4 biomarkers on fine needle aspirations, and ≥ 2 biomarkers on surgical resection specimens., Conclusion: Tissue stewardship is important to enable successful completion of genetic testing and informed NSCLC treatment decisions. Preliminary assessment of the investigational Oncomine Dx Target Test suggests it could facilitate access to multiple biomarker testing using small tissue samples to support therapy decisions for patients with advanced NSCLC., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: Patients with open-angle glaucoma (OAG) whose intraocular pressure is not adequately controlled by one medication have several treatment options in the US. This analysis evaluated direct costs of unilateral eye treatment with two trabecular micro-bypass stents (two iStents) compared to selective laser trabeculoplasty (SLT) or medications only., Materials and Methods: A population-based, annual state-transition, probabilistic, cost-of-care model was used to assess OAG-related costs over 5 years. Patients were modeled to initiate treatment in year zero with two iStents, SLT, or medications only. In years 1-5, patients could remain on initial treatment or move to another treatment option(s), or filtration surgery. Treatment strategy change probabilities were identified by a clinician panel. Direct costs were included for drugs, procedures, and complications., Results: The projected average cumulative cost at 5 years was lower in the two-stent treatment arm ($4,420) compared to the SLT arm ($4,730) or medications-only arm ($6,217). Initial year-zero costs were higher with two iStents ($2,810) than with SLT ($842) or medications only ($996). Average marginal annual costs in years 1-5 were $322 for two iStents, $777 for SLT, and $1,044 for medications only. The cumulative cost differences between two iStents vs SLT or medications only decreased over time, with breakeven by 5 or 3 years post-initiation, respectively. By year 5, cumulative savings with two iStents over SLT or medications only was $309 or $1,797, respectively., Limitations: This analysis relies on clinical expert panel opinion and would benefit from real-world evidence on use of multiple procedures and treatment switching after two-stent treatment, SLT, or polypharmaceutical initial approaches., Conclusions: Despite higher costs in year zero, annual costs thereafter were lowest in the two-stent treatment arm. Two-stent treatment may reduce OAG-related health resource use, leading to direct savings, especially over medications only or at longer time horizons.

Objective: To measure the impact of invasive aspergillosis infection on US hospital costs and financial performance across different patient populations., Methods: Hospital discharge data for patients with a primary or secondary diagnosis of aspergillosis were extracted from the 2003 Nationwide Inpatient Sample (NIS) and the fiscal year 2003 (FYO3) Medicare Provider Analysis and Review (MedPAR) file. The data on patient demographics, length of stay (LOS), hospital charges, estimated costs, and reimbursement levels were reported. After controlling for comorbidities, operative procedures, and diagnosis-related group (DRG) assignment, the clinical and economic outcomes were compared for patients with and without aspergillosis., Results: The NIS contains a total of over 38 million projected hospital discharges. From these, 10400 aspergillosis cases were identified across 171 DRGs, resulting in a US incidence rate of 36 per million per year. The mean age of aspergillosis patients was 55.6 years, with 53.4% male and 67.9% Caucasian. The median (mean) LOS per aspergillosis patient was 10 (17.7) days, with a median (mean) total hospital charge (THC) of $44,845 ($96,731). Among the patient subgroups analyzed, the median (mean) THC per patient ranged from $47,252 ($82,946) for HIV to $413,200 ($442,233) for bone marrow transplant (BMT). When compared to the non-aspergillosis patient population, the data showed a significant increase in LOS, THC, and hospital costs. Furthermore, the higher hospital costs associated with aspergillosis patients were not matched by similar increases in reimbursements, resulting in a greater financial loss for hospitals. The mean reimbursement-to-cost ratio for aspergillosis cases across the DRGs analyzed was 0.80., Conclusions: Aspergillosis affects a wide range of patient groups and has a negative economic impact across many DRGs. Improved prevention, diagnosis, and patient management strategies can help mitigate these effects on hospital financial performance.

Objective: To evaluate an audit of medical inpatient records., Design: Retrospective comparison of the quality of recording in inpatients' notes over three years (1988, 1989, 1990)., Setting: Central Middlesex Hospital., Materials: Random sample of 188 notes per year drawn systematically from notes from four selected one month periods and audited by two audit nurses and most hospital physicians., Main Measures: General quality of routine clerking, assessment, clinical management, and discharge, according to a standardised, criterion based questionnaire developed in the hospital., Results: 1988 was the year preceding the start of audit in the hospital, 1989 the year of active audit with implicit and loosely defined criteria, and 1990 the year after introduction and circulation of explicit criteria for note keeping. There was a significant trend over the three years in 21/56 items of the questionnaire, including recording of alcohol intake (x2 = 8.4, df = 1, p = 0.01), ethnic origin (x2 = 57, df = 1, p = 0.001), allergies and drug reactions (x2 = 10, df = 1, p = 0.01) at admission and of chest x ray findings (x2 = 8, df = 1, p = 0.01), final diagnosis (x2 = 5.6, df = 1, p = 0.025), and signed entries (x2 = 11.3, df = 1, p = 0.001). Documentation of discharge and notification of discharge to general practitioners was not significantly improved., Conclusions: Extended audit of note keeping failed to sustain an initial improvement in practice; this may be due to coincidental decline in feedback to doctors about their performance.

Objectives: To design an audit questionnaire and pilot its use by an audit assistant to monitor inpatient management of acute asthma and to compare the care given by chest physicians and general physicians., Design: Retrospective review by a chest physician and audit assistant of a random sample of 76 case records of patients by a criterion based questionnaire developed from hospital guidelines on management of acute asthma., Setting: One district general hospital., Patients: 76 adult patients with acute asthma: 38 admitted with a relevant primary diagnosis between April 1988 and March 1989 and a further 38 admitted through the accident and emergency department between April 1989 and March 1990., Main Outcome Measures: Conformity with recognised standards for assessment and management of acute asthma before and after the audit and by chest physicians and general physicians., Results: Age and sex did not differ significantly between the different groups of patients. Overall, deviations from the guidelines occurred in recording measures of severity of asthma, emergency treatment with beta 2 agonists (60/76, 79%) and steroids (43/76, 57%), and prescription of antibiotics in accordance with at least one criterion of the guidelines (29/45, 64%). Chest physicians were more rigorous than general physicians in recording severity measures, especially serum potassium concentration (chi 2 = 3.6, df = 1, p = 0.06), emergency steroid treatment within the correct period (chi 2 = 3.9, df = 1, p = 0.05), and referral for follow up at an outpatient chest clinic. Recording of arterial blood gas tensions improved significantly between the 1988-9 and 1989-90 samples (chi 2 = 7.0, df = 1, p = 0.08)., Conclusions: The questionnaire proved easy to use for both doctor and audit assistant. The audit improved few standards of care and emphasises the need for further reinforcement and feedback.

Objective: To evaluate the experience of a year's audit of care of medical inpatients., Design: Audit of physicians by monthly review of two randomly selected sets of patients' notes by 12 reviewers using a detailed questionnaire dedicated to standards of medical records and to clinical management. Data were entered into a database and summary statistics presented quarterly at audit meetings. Assessment by improvement in questionnaire scores and by interviewing physicians., Setting: 1 District general hospital., Participants: About 40 consultant physicians, senior registrars, and junior staff dealing with 140 inpatient records., Main Outcome Measures: Median scores (range 1 to 9) for each item in the questionnaire; two sets of notes were discussed monthly at "general" audit meetings and clinical management of selected common conditions at separate monthly meetings., Results: A significant overall increase in median scores for questions on record keeping occurred after the start of the audit (p less than 0.01), but interobserver variation was high. The parallel audit meetings on clinical management proved to be more successful than the general audits in auditing medical care and were also considered to be more useful by junior staff. CONCLUSIONS AND ACTION: Medical audit apparently resulted in appreciable improvements in aspects of care such as clerking and record keeping. Analysis of the scores of the general audits has led to the introduction of agreed standards that can be objectively measured and are being used in a further audit, and from the results of the audits of clinical management have been developed explicit guidelines, which are being further developed for criterion based audit.