Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye.

Changes in the anterior segment of the eye due to type 2 diabetes mellitus (T2DM) are not well-characterized, in part due to the lack of a reliable animal model. This study evaluated changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites, and ciliary body vasculature, in a rat model of T2DM compared with human eyes. Male Sprague-Dawley rats were fed a high-fat diet (45% fat) or normal diet, and rats fed the high-fat diet were injected with streptozotocin intraperitoneally to generate a model of T2DM. Cataract formation and corneal endothelial cell density were assessed using microscopic analysis. Diabetes-related rat aqueous humor alterations were assessed using metabolomics screening. Transmission electron microscopy was used to assess qualitative ultrastructural changes ciliary process microvessels at the site of aqueous formation in the eyes of diabetic rats and humans. Eyes from the diabetic rats demonstrated cataracts, lower corneal endothelial cell densities, altered aqueous metabolites, and ciliary body ultrastructural changes, including vascular endothelial cell activation, pericyte degeneration, perivascular edema, and basement membrane reduplication. These findings recapitulated diabetic changes in human eyes. These results support the use of this model for studying ocular manifestations of T2DM and support a hypothesis postulating blood-aqueous barrier breakdown and vascular leakage at the ciliary body as a mechanism for diabetic anterior segment pathology.

Pulmonary Aspects of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory virus that gains entry via angiotensin-converting enzyme 2 (ACE2) within airway epithelium. Patients exhibit a spectrum of respiratory symptoms from asymptomatic to respiratory failure. Patient factors including obesity, tobacco use, and black race are all associated with increased ACE2 expression and may contribute to increased complications. Consolidation and ground-glass opacities on chest imaging are typical but not specific for coronavirus disease 2019 (COVID-19). Venous thromboembolism occurs infrequently when prophylactic anticoagulation is provided. However, capillary microthrombosis is nearly ubiquitous, suggesting that it contributes to hypoxemia. Remdesivir and glucocorticoids may benefit some hospitalized patients. Many of those afflicted remain symptomatic two weeks following diagnosis and continue to require health care. Total lung capacity, diffusion capacity, and maximal oxygen consumption may be reduced for months in some survivors. Lung transplant offers chronically critically ill patients new hope, and this option may have increasing potential for outpatients with COVID-19-associated fibrosis.

Ultrasonographic evaluation of diaphragm thickness and excursion: correlation with weaning success in trauma patients: prospective cohort study.

PURPOSE: Prolonged mechanical ventilation (MV) subjects multiple trauma patients to ventilator-induced diaphragmatic dysfunction. There is limited evidence on the predictive role of diaphragm ultrasound (DUS) for weaning success in multiple trauma patients. Therefore, we evaluated Ultrasound of the diaphragm as a valuable indicator of weaning outcomes, in trauma patients. MATERIAL AND METHODS: This prospective cohort study included 50 trauma patients from September 2018 to February 2019. DUS was performed twice: upon ICU admission and the first weaning attempt. The diagnostic accuracy of indexes was evaluated by ROC curves. RESULTS: The study included patients with a mean age of 35.4 ± 17.37, and 78% being male. The median injury severity score was 75 (42-75). The failure group exhibited significantly lower right diaphragmatic excursion (DE) compared to the success group (P = 0.006). In addition, the failure group experienced a significant decrease in both right and left DE from admission to the first attempt of weaning from MV (P < 0.001). Both groups showed a significant decrease in inspiratory and expiratory thickness on both sides during weaning from MV compared to the admission time (P < 0.001). The findings from the ROC analysis indicated that the Rapid shallow breathing index (RSBI) (Sensitivity = 91.67, Specificity = 100), respiratory rate (RR)/DE (Right: Sensitivity = 87.5, Specificity = 92.31), and RR/TF (Thickening Fraction) (Right: Sensitivity = 83.33, Specificity = 80.77) demonstrated high sensitivity and specificity in predicting weaning outcome. CONCLUSION: In the context of patients with multiple trauma, employing DUC and assessing diaphragmatic excursion, thickness, RR/DE index, RR/TF index, and RSBI can aid in determining successful ventilator weaning.

Clinical Outcomes of Surgical Repair for Partial Distal Biceps Tendon Tears.

PURPOSE: The purpose of this study was to describe the outcomes of patients treated with surgical repair of partial tears of the distal biceps tendon. METHODS: The study was a retrospective review of repairs of partial tears of the distal biceps tendon performed by multiple surgeons from January 1, 2015 to October 15, 2020. Inclusion criteria consisted of preoperative magnetic resonance imaging indicative of distal biceps pathology without a complete tear and surgical treatment with intraoperative confirmation of a partial tear. The presence of preceding trauma, duration of symptoms, and postoperative complications were documented. Patients were contacted for outcome assessment using the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Patient-Reported Elbow Evaluation outcome measures. Clinical outcomes were obtained from 56 of 74 (76%) eligible patients with an average follow-up of 46 months (range: 15-85 months). RESULTS: After surgery, the median QuickDASH was 2.3 (interquartile range, 0-9.7), and the median Patient-Reported Elbow Evaluation score was 1 (interquartile range, 0-12). Postoperative QuickDASH scores were significantly lower than the preoperative scores. Known traumas preceding the symptoms and duration of symptoms before surgery were not significantly associated with the outcome. Of all eligible patients, 30 complications were reported in 25 (34%) patients and included 2 reruptures, 2 cases of heterotopic ossification, 1 deep infection, 1 case of implant irritation, 21 neuropraxias, and 3 hematomas. Five (7%) patients underwent 6 reoperations including 1 revision for a rerupture, 1 irrigation and debridement, 2 heterotopic ossification excisions, 1 hematoma evacuation, and 1 implant removal. CONCLUSIONS: The results suggest that the repair of partial distal biceps tendon tears is a viable treatment option with significant improvement in QuickDASH. There was no significant relationship between the postoperative outcome and duration of symptoms or known traumas preceding the symptoms. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Selective Patella Resurfacing in Contemporary Cruciate Retaining and Substituting Total Knee Arthroplasty: A Matched Cohort Analysis.

BACKGROUND: Leaving the patella unresurfaced in total knee arthroplasty (TKA) is increasing due to modern patella-friendly implants, awareness that complications are not uncommon with resurfacing, and knowledge that historical studies were scientifically confounded. This study examined the effect of selective patellar resurfacing on patient-reported outcome measures (PROMs) using modern implants and techniques in cohorts rigorously matched for demographics and osteoarthritis severity. METHODS: A total of 166 TKAs performed without patellar resurfacing were case-control matched to 166 TKAs with patella resurfacing. Case-control matching was based on demographics, American Society of Anesthesiology Physical Status, comorbidities, and osteoarthritis severity. No significant differences were observed between cohorts for demographics (P ≥ .347), comorbidities (P ≥ .443), or radiographic osteoarthritis severity (P ≥ .078). Radiographic alignment and prospectively collected PROMs were evaluated preoperatively and at latest clinical follow-up. RESULTS: Preoperatively, patellar tilt was less for the unresurfaced patella group (3 versus 4°, P = .003); however, postoperative patellar tilt was not different (3 versus 3°, P = .225). At a mean of 2.1 years follow-up (range, 1 to 7), University of California Los Angeles Activity Level was significantly higher for the unresurfaced patella group (6.3 versus 5.5, P = .002), but the mean group difference did not reach a minimal clinically important difference. There were no other significant differences in PROMs or reoperation rates between cohorts (P ≥ .135). CONCLUSION: In contemporary cruciate retaining and substituting TKA designs, not resurfacing the patella in select patients may achieve comparable PROMs and re-operation rates; and potentially greater activity level compared to patella resurfacing at early follow-up. LEVEL OF EVIDENCE: III.

Reconstruction of the Thumb Metacarpophalangeal Ulnar Collateral Ligament With an Adductor Pollicis Slip: An Anatomic Evaluation.

PURPOSE: Reconstruction of the ulnar collateral ligament (UCL) of the thumb metacarpophalangeal joint is commonly performed for chronic injuries. This study evaluates the anatomic feasibility of using a part of the adductor pollicis tendon to reconstruct UCL. METHODS: Ten cadaveric arms were dissected to evaluate the relationship between the insertions of UCL and the adductor pollicis. A slip of the adductor pollicis was divided from the tendon and transposed dorsally. The dissected tendon was deemed sufficient for reconstruction if it could be reflected to the footprint of the UCL origin. The size of the adductor pollicis slip was then compared with that of UCL. RESULTS: The dissected slip of the adductor pollicis could be fully reflected proximally to the UCL origin in all the specimens, and the insertion was also found to be closely approximated to the UCL insertion, averaging 2 mm distally and 0.6 mm dorsally. CONCLUSIONS: A sufficiently sized partial adductor pollicis tendon can be obtained to reconstruct UCL of the thumb metacarpophalangeal joint, and the location of the adductor pollicis insertion closely approximates that of the UCL insertion. CLINICAL RELEVANCE: The anatomic relationship evaluated in this study relates to a recently described method of the reconstruction of UCL of the thumb metacarpophalangeal joint that does not require free tendon harvest. This study shows that the technique is anatomically feasible.

Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness.

BACKGROUND: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).

Ventilated Patients With COVID-19 Show Airflow Obstruction.

OBJECTIVE: Many patients with coronavirus disease 2019 (COVID-19) need mechanical ventilation secondary to acute respiratory distress syndrome. Information on the respiratory system mechanical characteristics of this disease is limited. The aim of this study is to describe the respiratory system mechanical properties of ventilated COVID-19 patients. DESIGN, SETTING, AND PATIENTS: Patients consecutively admitted to the medical intensive care unit at the University of Iowa Hospitals and Clinics in Iowa City, USA, from April 19 to May 1, 2020, were prospectively studied; final date of follow-up was May 1, 2020. MEASUREMENTS: At the time of first patient contact, ventilator information was collected including mode, settings, peak airway pressure, plateau pressure, and total positive end expiratory pressure. Indices of airflow resistance and respiratory system compliance were calculated and analyzed. MAIN RESULTS: The mean age of the patients was 58 years. 6 out of 12 (50%) patients were female. Of the 21 laboratory-confirmed COVID-19 patients on invasive mechanical ventilation, 9 patients who were actively breathing on the ventilator were excluded. All the patients included were on volume-control mode. Mean [±standard deviation] ventilator indices were: resistive pressure 19 [±4] cmH2O, airway resistance 20 [±4] cmH2O/L/s, and respiratory system static compliance 39 [±16] ml/cmH2O. These values are consistent with abnormally elevated resistance to airflow and reduced respiratory system compliance. Analysis of flow waveform graphics revealed a pattern consistent with airflow obstruction in all patients. CONCLUSIONS: Severe respiratory failure due to COVID-19 is regularly associated with airflow obstruction.

A Prospective Analysis of Motor and Cognitive Skill Retention in Novice Learners of Point of Care Ultrasound.

OBJECTIVES: To identify the time at which point of care ultrasound static image recognition and image acquisition skills decay in novice learners. SETTING: The University of Iowa Hospitals and Clinics. SUBJECTS: Twenty-four subjects (23 first-year medical students and one first-year physician assistant student). DESIGN: The subjects completed an initial didactic and hands-on session with immediate testing of learned image acquisition and static image identification skills. INTERVENTIONS: Retesting occurred at 1, 4, and 8 weeks after the initial training session with no retraining in between. Image acquisition skills were obtained on the same healthy male volunteers, and the students were given no immediate feedback on their performance. The image identification skills were assessed with a 10 question test at each follow-up session. MEASUREMENTS AND MAIN RESULTS: For pleural ultrasound by 4 weeks, there was a significant decline of the ability to identify A-lines (p = 0.0065). For pleural image acquisition, there was no significant decline in the ability to demonstrate lung sliding. Conversely, cardiac image recognition did not significantly decline throughout the study, while the ability to demonstrate cardiac images at 4 weeks (parasternal short axis view) did (p = 0.0008). CONCLUSIONS: Motor and cognitive skills decay at different times for pleural and cardiac images. Future ultrasound curricula should retrain skills at a maximum of 8 weeks from initial training. They should focus more on didactic sessions related to image identification for pleural images, and more hands-on image acquisition training for cardiac images, which represents a novel finding.

Hemodynamic monitoring in the extracorporeal membrane oxygenation patient.

PURPOSE OF REVIEW: Hemodynamic monitoring in ECMO patients requires familiarity with the underlying pathophysiology and circulatory mechanics of extracorporeal flow. This review discusses the various monitoring modalities relevant to the management of patients on venovenous ECMO (VV ECMO) and venoarterial (VA ECMO). We emphasize tools to judge the adequacy of perfusion, predict the response to fluid boluses, measure right ventricular function, assess left ventricular distention (for VA ECMO), and monitor the process of weaning from ECMO. We emphasize how differences between VV ECMO and VA ECMO are reflected in distinct approaches to monitoring. RECENT FINDINGS: Point-of-care ultrasound and near-infrared spectroscopy can play a significant role in monitoring of global and regional perfusion. SUMMARY: Recent literature in hemodynamic monitoring of ECMO patients is discussed, with comparison of VV ECMO and VA ECMO. Many common monitoring tools lack validity during ECMO: by taking into account the unique physiology of the ECMO circulation, selected methods can aid in the care of these complex patients.

Hand Infections in the Immunocompromised Patient: An Update.

Physicians are increasingly caring for immunocompromised individuals owing, in part, to the improved treatments and the increased life expectancy in these patients. Presentation of a patient with hand infection can vary greatly depending on the patient's underlying immune status. It is important to recognize and treat the infections quickly and effectively owing to the higher morbidity and mortality that may result from ineffective or delayed treatment in this patient population. The purpose of this article is to provide an outline of the most common and some of the more exotic organisms causing hand infections in patients with human immunodeficiency virus/acquired immunodeficiency syndrome, diabetes, and patients on immunosuppressive treatment. We discuss presentation, clinical picture, evidence-based approaches in treatment, and possible complications. It is important to inform surgeons of the atypical presentation of hand infections and systemic infections with hand manifestation in immunocompromised patients in order to shorten time to accurate diagnosis and effective treatment.

An Official American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. Rehabilitation Protocols, Ventilator Liberation Protocols, and Cuff Leak Tests.

BACKGROUND: Interventions that lead to earlier liberation from mechanical ventilation can improve patient outcomes. This guideline, a collaborative effort between the American Thoracic Society and the American College of Chest Physicians, provides evidence-based recommendations to optimize liberation from mechanical ventilation in critically ill adults. METHODS: Two methodologists performed evidence syntheses to summarize available evidence relevant to key questions about liberation from mechanical ventilation. The methodologists appraised the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach and summarized the results in evidence profiles. The guideline panel then formulated recommendations after considering the balance of desirable consequences (benefits) versus undesirable consequences (burdens, adverse effects, and costs), the certainty in the evidence, and the feasibility and acceptability of various interventions. Recommendations were rated as strong or conditional. RESULTS: The guideline panel made four conditional recommendations related to rehabilitation protocols, ventilator liberation protocols, and cuff leak tests. The recommendations were for acutely hospitalized adults mechanically ventilated for more than 24 hours to receive protocolized rehabilitation directed toward early mobilization, be managed with a ventilator liberation protocol, be assessed with a cuff leak test if they meet extubation criteria but are deemed high risk for postextubation stridor, and be administered systemic steroids for at least 4 hours before extubation if they fail the cuff leak test. CONCLUSIONS: The American Thoracic Society/American College of Chest Physicians recommendations are intended to support healthcare professionals in their decisions related to liberating critically ill adults from mechanical ventilation.

Official Executive Summary of an American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults.

BACKGROUND: This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society and the American College of Chest Physicians. METHODS: A multidisciplinary panel posed six clinical questions in a Population, Intervention, Comparator, and Outcomes format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, the confidence in the evidence, the certainty about how much the public values the main outcomes, the magnitude and balance of desirable and undesirable outcomes, the resources and costs associated with the intervention, the impact on health disparities, and the acceptability and feasibility of the intervention. RESULTS: Evidence-based recommendations were formulated and graded initially by subcommittees and then modified after full-panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation. CONCLUSIONS: The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and Chest.

Incidence and Outcomes of Positive Donor Corneoscleral Rim Fungal Cultures after Keratoplasty.

PURPOSE: To determine the incidence of positive corneoscleral donor rim fungal cultures after keratoplasty and to report clinical outcomes of grafts with culture-positive donor rims. DESIGN: Retrospective cohort study. PARTICIPANTS: Consecutive donor corneas and keratoplasty recipients at a single tertiary referral center over 20 years. METHODS: Patient charts were reviewed to determine the incidence of positive donor rim fungal cultures and clinical outcomes of all grafts using contaminated tissue. MAIN OUTCOME MEASURES: The primary outcome measures were positive donor rim fungal culture results and the development of postkeratoplasty fungal infection using corresponding corneal tissue. The secondary outcome measure was the impact of postoperative prophylaxis on donor tissue-associated infections. RESULTS: A total of 3414 keratoplasty cases were included in the statistical analysis. Seventy-one cases (2.1%) were associated with a fungal culture-positive donor rim. Candida species were cultured in 40 cases (56.3%). There was a higher incidence of positive rim cultures over the last 5 years of the analytic period compared with the first 15 years (P = 0.018). Fungal keratitis developed in 4 cases (5.6%), and all patients required further surgical intervention to achieve cure. There were no cases of fungal endophthalmitis. Empiric antimycotic prophylaxis initiated at the time of positive culture result reduced the incidence of keratitis from 15.8% in untreated cases to 1.9% in treated cases (P = 0.056). CONCLUSIONS: Positive donor rim fungal cultures are uncommon, but carry an unacceptably high risk of postoperative fungal infection. This risk may be reduced with prophylactic antimycotic therapy when culture-positive donor rims are identified.

Descemet membrane adhesion strength is greater in diabetics with advanced disease compared to healthy donor corneas.

Descemet membrane endothelial keratoplasty (DMEK) is an increasingly popular surgical procedure for treating ocular diseases that require a corneal transplant. Previous studies have found that tissue tearing during surgical preparation is more likely elevated in eyes from donors with a history of diabetes mellitus. To quantify these potential differences, we established an experimental technique for quantifying the force required to separate the endothelium-Descemet membrane complex (EDM) from stroma in human donor corneal tissue, and we assessed differences in adhesion strength between diabetic and non-diabetic donor corneas. Transplant suitable corneas were obtained from 23 donors 50-75 years old with an average preservation to assay time of 11.5 days. Corneas were classified from a medical records review as non-diabetic (ND, n = 9), diabetic without evidence of advanced disease (NAD, n = 8), or diabetic with evidence of advanced disease (AD, n = 10). Corneas were sectioned into 3 mm wide strips and the EDM peeled from the stroma. Using the force-extension data obtained from mechanical peel testing, EDM elastic peel tension (TE), elastic stiffness (SE), average delamination tension (TD), and maximum tension (TMAX) were calculated. Mean TE, SE, TD, and TMAX values for ND corneas were 0.78 ± 0.07 mN/mm, 0.37 ± 0.05 mN/mm/mm, 0.78 ± 0.08 mN/mm, and 0.94 ± 0.17 mN/mm, respectively. NAD values did not differ significantly. However, AD values for TE (1.01 ± 0.18 mN/mm), TD (1.09 ± 0.21 mN/mm), and TMAX (1.37 ± 0.24 mN/mm) were greater than ND and NAD corneas (P < 0.05). SE did not differ significantly between groups. These findings provide proof of the concept that chronic hyperglycemia from diabetes mellitus results in a phenotypically more adhesive interface between Descemet membrane and the posterior stroma in donor corneal tissue. Results of this study provide a foundation for further investigations into the impact of diabetes on the posterior cornea, eye banking, and keratoplasty.

Exercise-induced pulmonary hemorrhage in a nonathlete: case report and review of physiology.

The integrity of the pulmonary blood-gas barrier is vulnerable to intense exercise in elite athletes, similar to the phenomenon of exercise-induced pulmonary hemorrhage in thoroughbred racehorses. A 50-year-old previously healthy man presented with acute onset shortness of breath, dry cough, and hypoxemia after engaging in an extremely vigorous game of handball. CT scan of the chest showed diffuse patchy air-space disease. Bronchoalveolar lavage revealed diffuse alveolar hemorrhage. Infectious etiologies and bleeding diatheses were excluded by laboratory testing. Serological tests for ANCA-associated vasculitis, lupus, and Goodpasture's disease also were negative. A transthoracic echocardiogram was normal. The patient recovered completely on supportive therapy in less than 72 h. This case demonstrates strenuous exercise as a cause of diffuse alveolar hemorrhage in a previously healthy male with no apparent underlying cardiopulmonary disease.

Using a Cone-Shaped Glass Funnel Adapter Reduces Endothelial Cell Loss Caused by Preloading Descemet Membrane Endothelial Keratoplasty Tissue.

PURPOSE: The aims of this study were (1) to compare "front" and "rear" methods for loading Descemet membrane endothelial keratoplasty (DMEK) tissue into both micro-Jones and standard-Jones tubes and (2) to evaluate the efficacy of a cone-shaped glass funnel adapter designed to make loading DMEK tissue safer for corneal endothelial cells. METHODS: The corneal endothelium was stained with 0.06% trypan blue to confirm equivalence between mate corneas. The tissues were then processed using the Iowa Lions Eye Bank standard DMEK protocol. In comparison 1, one mate was loaded into the rear of a micro-Jones or standard-Jones tube and the other was loaded into the front of the same tube. In comparison 2, one mate was loaded into the front of the micro-Jones tube and the other was loaded through the cone-shaped funnel adapter into the rear. All tissues were ejected through the front of the modified Jones tubes and assessed for endothelial cell loss (ECL) with calcein AM staining, FIJI, and Trainable Weka Segmentation; scroll widths were measured digitally. RESULTS: There were no statistically significant differences in ECL between front and rear loading [micro (N = 6 pairs): front 15.74% vs. rear 17.95%; standard (N = 6 pairs): front 19.58% vs. rear 19.17%; all P > 0.05]. DMEK scrolls loaded with the funnel adapter exhibited lower ECL compared with scrolls loaded through the front [micro (N = 8 pairs): front 13.53% vs. loading funnel 2.40%; P < 0.001]. Loading with the adapter was not faster (front 6.66 seconds vs. loading funnel 5.52 seconds; P = 0.24). CONCLUSIONS: Using a cone-shaped DMEK loading funnel may reduce ECL sustained during preloading.

Long-term outcomes after treatment of delirium during critical illness with antipsychotics (MIND-USA): a randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Delirium is common during critical illness and is associated with long-term cognitive impairment and disability. Antipsychotics are frequently used to treat delirium, but their effects on long-term outcomes are unknown. We aimed to investigate the effects of antipsychotic treatment of delirious, critically ill patients on long-term cognitive, functional, psychological, and quality-of-life outcomes. METHODS: This prespecified, long-term follow-up to the randomised, double-blind, placebo-controlled phase 3 MIND-USA Study was conducted in 16 hospitals throughout the USA. Adults (aged ≥18 years) who had been admitted to an intensive care unit with respiratory failure or septic or cardiogenic shock were eligible for inclusion in the study if they had delirium. Participants were randomly assigned-using a computer-generated, permuted-block randomisation scheme with stratification by trial site and age-in a 1:1:1 ratio to receive intravenous placebo, haloperidol, or ziprasidone for up to 14 days. Investigators and participants were masked to treatment group assignment. 3 months and 12 months after randomisation, we assessed survivors' cognitive, functional, psychological, quality-of-life, and employment outcomes using validated telephone-administered tests and questionnaires. This trial was registered with ClinicalTrials.gov, NCT01211522, and is complete. FINDINGS: Between Dec 7, 2011, and Aug 12, 2017, we screened 20 914 individuals, of whom 566 were eligible and consented or had consent provided to participate. Of these 566 patients, 184 were assigned to the placebo group, 192 to the haloperidol group, and 190 to the ziprasidone group. 1-year survival and follow-up rates were similar between groups. Cognitive impairment was common in all three treatment groups, with a third of survivors impaired at both 3-month and 12-month follow-up in all groups. More than half of the surveyed survivors in each group had cognitive or physical limitations (or both) that precluded employment at both 3-month and 12-month follow-up. At both 3 months and 12 months, neither haloperidol (adjusted odds ratio 1·22 [95% CI 0·73-2.04] at 3 months and 1·12 [0·60-2·11] at 12 months) nor ziprasidone (1·07 [0·59-1·96] at 3 months and 0·94 [0·62-1·44] at 12 months) significantly altered cognitive outcomes, as measured by the Telephone Interview for Cognitive Status T score, compared with placebo. We also found no evidence that functional, psychological, quality-of-life, or employment outcomes improved with haloperidol or ziprasidone compared with placebo. INTERPRETATION: In delirious, critically ill patients, neither haloperidol nor ziprasidone had a significant effect on cognitive, functional, psychological, or quality-of-life outcomes among survivors. Our findings, along with insufficient evidence of short-term benefit and frequent inappropriate continuation of antipsychotics at hospital discharge, indicate that antipsychotics should not be used routinely to treat delirium in critically ill adults. FUNDING: National Institutes of Health and the US Department of Veterans Affairs.