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Capnography has been widely adopted in multiple clinical areas. The capnogram and end-tidal carbon dioxide offer a wealth of information, in the right clinical setting, and when properly interpreted. In this article, the authors aim to review the most common clinical scenarios during which capnography has been shown to be of benefit. This includes the areas of fluid responsiveness, cardiopulmonary resuscitation, and conscious sedation. They review the published literature, highlighting its pitfalls and identifying its limitations.

Background Reconstruction of the radial collateral ligament (RCL) of the thumb metacarpophalangeal (MP) joint is commonly performed for chronic injuries. This study aims to evaluate the anatomical feasibility and reliability of using the abductor pollicis brevis (APB) tendon to reconstruct the RCL. Methods Ten cadaver arms were dissected to evaluate the relationship between insertions of the RCL and APB. A slip of the APB was divided from tendon and reflected proximally. The dissected tendon was deemed sufficient for reconstruction if it could be reflected to the footprint of the RCL origin. The size of the dissected APB slip was then compared with that of the RCL. Results The dissected slip of the APB could be fully reflected proximally to the RCL origin in all specimens. The APB insertion was also found to be closely approximated to the RCL insertion, averaging 2.1 mm distal and 1.8 mm dorsal. Significant differences existed between the lengths ( P < .001) of the APB slip and RCL, with no significant difference in widths ( P = .051). Conclusions A sufficient APB tendon slip can be obtained to reliably reconstruct the RCL of the thumb MP. The location of the APB insertion closely approximates the RCL insertion.

The purpose of this study was to describe the outcomes of patients treated with surgical repair of partial tears of the distal biceps tendon.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).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.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.Therapeutic IV.

Fuchs endothelial corneal dystrophy (FECD), a progressive polygenic disease that causes degeneration of the corneal endothelium, is the leading indication for corneal transplantation in the U.S. Characteristically, loss of corneal endothelial cells and formation of degenerative extracellular “guttae” result in failure to maintain appropriate corneal hydration through active ion pumping to counter the passive leakage of aqueous humor. FECD pathogenesis is linked to oxidative stress and environmental exposure to ultraviolet A (UVA), and impaired endogenous response to oxidative stress is common to the disease across multiple genotypes. UV irradiation is also known to cause cellular damage by ferroptosis, a nonapoptotic oxidative cell death resulting from iron-mediated lipid peroxidation. Although a possible role for ferroptosis in FECD has been postulated to account for the increased susceptibility to oxidative damage and lipid peroxidation, this has not been explored systematically. In this study, we investigated the roles of genetic background and UVA exposure in causing lipid membrane damage and endothelial cell degeneration in FECD. We first sought clinical evidence of iron-mediated lipid peroxidation in surgical samples obtained from FECD patients undergoing endothelial keratoplasty, and found increased levels of cytosolic ferrous iron (Fe2+) and evidence of lipid peroxidation were present in end-stage diseased tissues compared with healthy human donor corneas. Next, using immortalized (F35T) and primary cell cultures modeling the TCF4 intronic trinucleotide repeat expansion genotype, we found that alterations in gene and protein expression involved in ferroptosis were conserved in both cell culture and tissue models of FECD disease compared to controls, including elevated levels of the ferroptosis-specific marker transferrin receptor 1. F35T immortalized cells showed significantly higher basal lipid peroxidation than control HCEC-B4G12 cells, indicating higher susceptibility to ferroptosis attributable to genetic background. Then, we tested the impact of physiologically relevant doses of UVA irradiation on F35T cell cultures and found increased cytosolic Fe2+ iron levels indicating a role for ferroptosis in FECD disease progression. Finally, we tested the effects of inhibitory ferroptosis molecules. We found that F35T cells were more prone to RSL3 induced ferroptosis than healthy controls with deferoxamine chelation which indicated increased susceptibility in FECD cells, and cell death could be prevented after experimentally-induced ferroptosis using solubilized antioxidant ubiquinol indicating a role for anti-ferroptosis therapies. This investigation demonstrates that FECD genetic background and UVA exposure contribute to basal and incidental iron-mediated lipid peroxidation and cell death in FECD, and provides the basis for future investigations of ferroptosis-mediated oxidative damage and disease progression in FECD.

Objective Currently, there are limited markers to predict the osteoporosis probability in patients with primary hyperparathyroidism. We studied the relationship between various parameters and results of DXAs at various skeletal sites. Methods Retrospective review of data for 218 patients with primary hyperparathyroidism was performed. Age, BMI, bone mineral density, serum total calcium, ionized calcium, intact parathyroid hormone, albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-hour urinary calcium levels and parathyroid tumor weight were analyzed. Two different statistical models- linear regression and multivariate logistic regression were performed. Results At the lumbar spine, with the linear model, BMI (P At the femoral neck, BMI (P At the total hip, BMI (P Conclusion In patients with primary hyperparathyroidism, BMI strongly correlated with T scores and probability of osteoporosis.

Purpose Rho-associated kinase (ROCK) inhibitors have been successfully used as a rescue strategy in eyes that failed to clear after descemetorhexis without endothelial graft for treatment of Fuchs endothelial corneal dystrophy (FECD). The functional mechanisms by which ROCK inhibitors modulate corneal endothelial cell regeneration in FECD patients have, however, not been clarified. Here, we analyzed the effect of the ROCK inhibitor ripasudil on corneal endothelial cells of FECD patients and normal donors using ex vivo tissue and in vitro cellular models. Design Experimental study: laboratory investigation. Methods This institutional study used endothelial cell–Descemet membrane lamellae from FECD patients (n = 450) undergoing Descemet membrane endothelial keratoplasty (FECD ex vivo model), normal research-grade donor corneas (n = 30) after scraping off central endothelial cells (ex vivo wound healing model), normal donor corneas (n = 20) without endothelial injury, and immortalized cell lines (n = 3) generated from FECD patients (FECD in vitro model). Descemet membrane lamellae were dissected into halves and incubated for 24-72 hours in storage medium with or without a single dose of 30 μM ripasudil. The effects of ripasudil on expression of genes and proteins related to endothelial cell proliferation, migration, functionality, and endothelial-to-mesenchymal transition were analyzed and complemented by functional assays on FECD cell lines. Results A single dose of ripasudil induced significant upregulation of genes and proteins related to cell cycle progression, cell-matrix adhesion and migration, as well as endothelial barrier and pump function up to 72 hours, whereas classical markers of endothelial-to-mesenchymal transition were downregulated in both FECD and normal specimens compared to unstimulated controls ex vivo. In addition to stimulation of proliferation and migration, ripasudil-induced changes in expression of functional signature genes could be also verified in FECD cell lines in vitro. Conclusions These data support the concept that inhibition of ROCK signaling represents a potent tool in regenerative therapies in FECD patients through reactivation of cell proliferation and migration as well as restoration of endothelial pump and barrier function without inducing adverse phenotypic changes.

Purpose To create a simplified critical illness severity scoring system with high prediction accuracy for 30-day mortality using only commonly available variables. Materials and methods This is a retrospective cohort study of ICU admissions 2010–2015 in 306 ICUs in 117 Veterans Affairs (VA) hospitals. We randomly divided our cohort into a training dataset (75%) and a validation dataset (25%). We created a critical illness severity scoring system (CISSS) using age, comorbidities, heart rate, mean arterial blood pressure, temperature, respiratory rate, hematocrit, white blood cell count, creatinine, sodium, glucose, albumin, bilirubin, bicarbonate, use of invasive mechanical ventilation, and whether the admission was surgical or not. We validated the performance of CISSS to predict 30-day mortality internally. Results After excluding 31,743 re-admissions, we divided our sample (n = 534,001) into a training (n = 400,613) and a validation dataset (n = 133,388). In the training dataset, the area under the curve (AUC) of CISSS was 0.847(95%CI = 0.845–0.850). In the validation dataset, the AUC was 0.848 (95%CI = 0.844–0.852), the standardized mortality ratio (SMR) was 1.00 (95%CI = 0.98–1.02), and Brier's score for 30-day mortality was 0.058 (95%CI = 0.057–0.059). CISSS calibration was acceptable. Conclusions CISSS has very good performance and requires only commonly used variables that can be easily extracted by electronic health records.

Purpose To determine whether ubiquinol improves mitochondrial function and cell viability in human donor corneal endothelial cells during hypothermic corneal tissue storage. Methods Endothelial cell Descemet membrane tissues were treated with 10 μM ubiquinol, the reduced form of the antioxidant coenzyme Q10, for 5 days in Optisol-GS storage media before assaying for mitochondrial activity using extracellular flux analysis of oxygen consumption. In addition, endothelial cell Descemet membrane tissues were analyzed for cell viability using apoptosis and necrosis assays. Control tissues from mate corneas were treated with diluent only, and comparisons were analyzed for differences. Results A total of 13 donor corneal tissues with a mean (SEM) preservation time of 11.8 days (0.4) were included for the analysis. Treatment with 10 μM ubiquinol increased spare respiratory capacity by 174% (P = 0.001), maximal respiration by 93% (P = 0.003), and proton leak by 80% (P = 0.047) compared with controls. Cells treated with ubiquinol had no significant change in cell necrosis or apoptosis. Conclusions Preliminary testing in donor corneal tissue at specified doses indicates that ubiquinol may be a useful biocompatible additive to hypothermic corneal storage media that increases corneal endothelial cell mitochondrial function. Additional investigations are indicated to further study and optimize the dose and formulation of ubiquinol for use in preserving donor corneal tissue function during hypothermic storage.

This article reviews the longstanding debate in the literature on electoral systems regarding the relative merits of open and closed lists for the election of women, describes the very different systems used in congressional and municipal elections in Peru, and examines gendered disparities between Lima and the provinces. A series of empirical comparisons demonstrates that the type of list is not of great importance in the capital, but that female candidates fare better under closed lists in the provinces, where the socioeconomic context and political culture are less supportive of women., Este artículo analiza el prolongado debate existente en la bibliografía sobre los méritos relativos para la elección de mujeres a través de listas abiertas y cerradas; describe los muy distintos sistemas empleados en las elecciones congresales y municipales en el Perú; y examina las disparidades existentes entre Lima y las provincias del país desde una perspectiva de género. Una serie de comparaciones empíricas demuestran que el tipo de listas no reviste mayor importancia en la capital, pero que las listas cerradas favorecen mucho más a candidatas mujeres en provincias, donde el contexto socioeconómico y la cultura política alientan menos a las mujeres.

The degree of osteoarthritis (OA) acceptable to leave in a native patella during unresurfaced total knee arthroplasty (TKA) remains unknown. This study's purpose was to examine the effect of patellofemoral OA severity on patient-reported outcome measures (PROMs) in primary TKAs performed without patellar resurfacing.One hundred ninety-three primary TKAs performed without patellar resurfacing were retrospectively reviewed. Preoperative patellofemoral OA severity was graded on severity, marginal osteophytes, joint space narrowing, and chondral damage using accepted grading systems. Patellar tilt and tibiofemoral alignment were measured radiographically. PROMs were evaluated at a minimum of 1-year follow-up.In multivariate regression, preoperative lateral patella Kellgren-Lawrence grade ≥2 was associated with superior change in Knee Society Score pain with level walking, higher absolute change in Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (P ≤ 0.029), and knees ‟always feeling normal" (odds ratio [OR] 3.12; P = 0.005). Osteoarthritis Research Society International atlas grades and Outerbridge classification scores did not significantly influence PROMs.Worse preoperative OA severity in the lateral patellar facet, graded with the Kellgren-Lawrence system, predicted superior knee-specific PROMs in patients with unresurfaced patellae after contemporary TKA. This observation supports the clinical finding that patients with more severe OA have optimized patient outcomes and highlights the minimal contribution of patella OA to knee function after primary TKA.

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.

For much of its brief history, extracorporeal life support (ECLS) has been accompanied by endotracheal intubation, supine positioning, deep sedation, and therapeutic paralysis—treatments that prevent, or greatly impede, mobilization. Yet, for many modern ECLS patients, especially those with single-organ lung failure treated with venovenous support, these are no longer necessary, opening the door to early physical therapy. Moving the ECLS patient is no small task. Nevertheless, modern technology; an attentive, well-trained team; and a culture of liberation join to get the carefully selected ECLS patient moving. This chapter explores the impact of newer circuits, pumps, and cannulas; accumulating data on the ravages of sedation and bed rest during critical illness; and early experiences with mobilization. Together, these offer a novel vision for ECLS; one in which extracorporeal gas exchange frees the patient from a range of noxious interventions, potentially improving outcomes.

To identify the time at which point of care ultrasound static image recognition and image acquisition skills decay in novice learners.The University of Iowa Hospitals and Clinics.Twenty-four subjects (23 first-year medical students and one first-year physician assistant student).The subjects completed an initial didactic and hands-on session with immediate testing of learned image acquisition and static image identification skills.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.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).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.

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.

Purpose To determine the concentration of amphotericin B that would be both effective against Candida albicans contamination and safe for corneal endothelial cells (CECs) in cold storage conditions. Methods Triplicate media cultures were inoculated with 10 colony-forming units (CFUs)/mL of C. albicans (American Type Culture Collection 10231), supplemented with amphotericin B (0-20 μg/mL), stored in cold conditions (2°C-8°C) for 72 hours, and analyzed quantitatively for CFUs. C. albicans concentration in each sample was determined initially and after 6, 24, 48, and 72 hours of storage. CEC mitochondrial function (oxygen consumption rate), apoptosis, and necrosis were examined in donor corneas after 7 days of amphotericin B exposure and compared with untreated controls. CEC viability was also examined by calcein-AM staining and Fiji segmentation after 72 hours or 2 weeks of amphotericin B exposure to mimic potential eye bank practices. Results Amphotericin B concentrations of 1.25, 2.5, and 5.0 μg/mL resulted in 0.47, 1.11, and 1.21 log10 CFU reduction after only 6 hours of cold storage and continued to decrease to 3.50, 3.86, and 4.49 log10 reductions after 72 hours, respectively. By contrast, amphotericin B 0.255 µg/mL showed only 1.01 log10 CFU reduction after 72 hours of incubation. CEC mitochondrial function and viability did not differ in donor corneas exposed to amphotericin B ≤2.59 μg/mL compared with the controls. Conclusions Optimal efficacy of amphotericin B against C. albicans is achieved in cold storage conditions at concentrations ≥1.25 μg/mL, and 2.5 μg/mL reduces Candida contamination by >90% after 6 hours of cold storage without sacrificing CEC health.

To determine how the Rho kinase inhibitor, ripasudil, affects metabolic function and cell viability in donor human corneal endothelial cells (HCECs).Endothelial cell-Descemet membrane (EDM) tissues were treated with 10 μM ripasudil and assayed for mitochondrial and glycolytic activity using extracellular flux analysis and then compared to untreated controls. In addition, EDM tissues with a 24-h ripasudil treatment and control tissues were exposed to 1 μM staurosporine to induce apoptosis and then analyzed for cell viability using apoptosis and necrosis assays.Mitochondrial respiration metrics, specifically maximal respiration (P = 0.758) and spare respiratory capacity (P = 0.777), did not differ among the 1-h ripasudil treatment, 24-h treatment, and untreated tissues. Glycolytic activity assays showed an increase in glycolytic capacity at 1 h compared to the 24-h exposure group (P = 0.049) and controls (P = 0.009). Following exposure to staurosporine, the percentage of apoptotic HCECs was lower (P = 0.009) in ripasudil-treated tissues (2.473%, standard error of the mean [SEM] 0.477%) compared to untreated controls (3.349%, SEM 0.566%). In contrast, the percentage of necrotic HCECs decreased but did not differ statistically (P = 0.158) between ripasudil-treated (3.789%, SEM 0.487%) and untreated (4.567%, SEM 0.571%) tissues.Exposures to ripasudil did not result in any detectable reduction in metabolic function for HCECs in an ex vivo donor tissue model, and an increase in glycolytic activity at the 1-h time point was detected. In addition, HCECs treated with ripasudil gained a protective effect against induced apoptosis, suggesting that ripasudil may help improve the integrity of the corneal endothelium.

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.

Mitochondrial function is essential for the viability of aerobic eukaryotic cells, as mitochondria provide energy through the generation of adenosine triphosphate (ATP), regulate cellular metabolism, provide redox balancing, participate in immune signaling, and can initiate apoptosis. Mitochondria are dynamic organelles that participate in a cyclical and ongoing process of regeneration and autophagy (clearance), termed mitophagy specifically for mitochondrial (macro)autophagy. An imbalance in mitochondrial function toward mitochondrial dysfunction can be catastrophic for cells and has been characterized in several common ophthalmic diseases. In this article, we review mitochondrial homeostasis in detail, focusing on the balance of mitochondrial dynamics including the processes of fission and fusion, and provide a description of the mechanisms involved in mitophagy. Furthermore, this article reviews investigations of ocular diseases with impaired mitophagy, including Fuchs endothelial corneal dystrophy, primary open-angle glaucoma, diabetic retinopathy, and age-related macular degeneration, as well as several primary mitochondrial diseases with ocular phenotypes that display impaired mitophagy, including mitochondrial encephalopathy lactic acidosis stroke, Leber hereditary optic neuropathy, and chronic progressive external ophthalmoplegia. The results of various studies using cell culture, animal, and human tissue models are presented and reflect a growing awareness of mitophagy impairment as an important feature of ophthalmic disease pathology. As this review indicates, it is imperative that mitophagy be investigated as a targetable mechanism in developing therapies for ocular diseases characterized by oxidative stress and mitochondrial dysfunction.

Defective cellular metabolism, impaired mitochondrial function, and increased cell death are major problems that adversely affect donor tissues during hypothermic preservation prior to transplantation. These problems are thought to arise from accumulated reactive oxygen species (ROS) inside cells. Oxidative stress acting on the cells of organs and tissues preserved in hypothermic conditions before surgery, as is the case for cornea transplantation, is thought to be a major reason behind cell death prior to surgery and decreased graft survival after transplantation. We have recently discovered that ubiquinol – the reduced and active form of coenzyme Q10 and a powerful antioxidant – significantly enhances mitochondrial function and reduces apoptosis in human donor corneal endothelial cells. However, ubiquinol is highly lipophilic, underscoring the need for an aqueous-based formulation of this molecule. Herein, we report a highly dispersible and stable formulation comprising a complex of ubiquinol and gamma cyclodextrin (γ-CD) for use in aqueous-phase ophthalmic products. Docking studies showed that γ-CD has the strongest binding affinity with ubiquinol compared to α- or β-CD. Complexed ubiquinol showed significantly higher stability compared to free ubiquinol in different aqueous ophthalmic products including Optisol-GS® corneal storage medium, balanced salt solution for intraocular irrigation, and topical Refresh® artificial tear eye drops. Greater ROS scavenging activity was noted in a cell model with high basal metabolism and ROS generation (A549) and in HCEC-B4G12 human corneal endothelial cells after treatment with ubiquinol/γ-CD compared to free ubiquinol. Furthermore, complexed ubiquinol was more effective at lowering ROS, and at far lower concentrations, compared to free ubiquinol. Complexed ubiquinol inhibited lipid peroxidation and protected HCEC-B4G12 cells against erastin-induced ferroptosis . No evidence of cellular toxicity was detected in HCEC-B4G12 cells after treatment with complexed ubiquinol. Using a vertical diffusion system, a topically applied inclusion complex of γ-CD and a lipophilic dye (coumarin-6) demonstrated transcorneal penetrance in porcine corneas and the capacity for the γ-CD vehicle to deliver drug to the corneal endothelium. Using the same model, topically applied ubiquinol/γ-CD complex penetrated the entire thickness of human donor corneas with markedly greater ubiquinol retention in the endothelium compared to free ubiquinol. Lastly, the penetrance of ubiquinol/γ-CD complex was assayed using human donor corneas preserved for 7 days in Optisol-GS® per standard industry practices, and demonstrated higher amounts of ubiquinol retained in the corneal endothelium compared to free ubiquinol. In summary, ubiquinol complexed with γ-CD is a highly stable composition that can be incorporated into a variety of aqueous-phase products for ophthalmic use including donor corneal storage media and topical eye drops to scavenge ROS and protect corneal endothelial cells against oxidative damage .

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.

Objective: To present a case of pyknodysostosis (PKND), a rare genetic cause of skeletal dysplasia that often goes undiagnosed even in patients with classic features. Methods: We report a case of PKND that went undiagnosed over many years despite classic features. We performed physical examination, imaging studies, and genetic testing on the patient. Results: A 21-year-old female presented to endocrinology to establish care. On evaluation, she was noted to have disproportionate short stature and a past medical history notable for bilateral blindness due to optic atrophy secondary to bone enlargement and thickening of the optic nerve canal before age 7 years. She also had a history of foot fractures occurring with ambulation. Her family history was significant for consanguineous parents and relatives with similar clinical features. Physical examination revealed a short, 128-cm tall female with open anterior and mastoid fontanels, mild frontal bossing and micrognathia, evidence of double rows of teeth, and digits of varied length in both hands and feet. Plain radiographs demonstrated diffuse sclerosis and marked cortical thickening of the pelvis, femurs, metacarpals, proximal phalanges, and metatarsals as well as decreased phalangeal length and acro-osteolysis of the hands and feet. Dual energy X-ray absorptiometry demonstrated increased bone mineral density (z scores +2.5 lumbar spine, +3.7 femoral neck, +4.5 total hip). Genetic testing revealed a exon 5-homozygous mutation in the cathepsin K (CTSK) gene consistent with PKND. Conclusion: Patients with PKND come to medical attention for a variety of reasons but often go undiagnosed even when presenting with classic features due to the rarity of the condition and the overlap with other skeletal dysplasias. Abbreviations: CTSK cathepsin K PKND pyknodysostosis

Critical illness can threaten the adequacy of O2 delivery or CO2 excretion. Monitoring seeks to identify the adequacy of oxygenation and ventilation and to detect deterioration early. Advances in oximetry, capnography, and transcutaneous CO2 monitoring offer new opportunities for more accurate estimation of gas exchange, noninvasive monitoring of parameters previously not amenable (eg, total hemoglobin measurement), detection of disease, and prediction of fluid responsiveness.

Purpose To assess how trypan blue staining affects Descemet membrane endothelial keratoplasty (DMEK) graft visibility and corneal endothelial cell (CEC) mitochondrial respiration. Methods DMEK grafts (n = 20) were stained with trypan blue 0.06% for 1, 3, 5, or 10 minutes. Each graft was injected into an artificial anterior chamber. Surgery was simulated with tapping and sweeping motions on the corneal surface and injections of balanced salt solution (BSS). Graft visibility was assessed at 5, 10, 20, and 30 minutes. Effects of trypan blue on mitochondrial respiration were assessed using primary CECs cultured from donor corneas (n = 43). Treatment wells exposed to trypan blue 0.06% (1, 5, or 30 minutes) and donor-matched control wells to methylene blue 1% (1 minute) or BSS (1, 5, or 30 minutes) were assayed for key respiration parameters. Results After 5 minutes of surgical manipulation, grafts stained for 5 minutes were significantly more visible than grafts stained for 1 or 3 minutes; there was no added benefit of staining for 10 minutes. After 10 minutes of surgical manipulation, grafts stained for 3 minutes were more visible than grafts stained for 1 minute, without additional benefits of staining ≥5 minutes. No visibility differences were observed after ≥20 minutes of surgical manipulation. CEC mitochondrial respiration did not change significantly following trypan blue exposure for all intervals tested compared to BSS. Conclusions Staining DMEK grafts with trypan blue for 3 to 5 minutes optimizes visibility during surgical manipulation without mitochondrial impairment. Corneal surgeons learning DMEK will benefit from optimizing this critical step.

The goal of the cardiopulmonary system is to supply oxygen and other nutrients to body tissues while eliminating carbon dioxide, and the heart and lung work closely together to achieve these ends. Because the heart and lung share volume and pressures within the thorax, each system tends to alter the other, especially when there is preexisting heart or lung disease, or when challenged by rising demand. Cardiopulmonary interactions are mediated by changes in pleural pressure (Ppl), lung volume, and gas exchange, all explored in the sections to follow.

PURPOSE To quantify changes in endothelial cell density (ECD) of donor corneal tissue in relation to the presence or absence of a medical history of diabetes mellitus diagnosis, treatment, and complications. METHODS A retrospective review was performed for all corneas collected at Iowa Lions Eye Bank between January 2012 and December 2015. For purposes of analysis, donor corneas were divided into 4 groups: nondiabetic, non-insulin-dependent diabetic, insulin-dependent diabetic without medical complications due to diabetes, and insulin-dependent diabetic with medical complications due to diabetes. ECD values (obtained through specular microscopy) and transplant suitability for endothelial transplantation (determined by the standard protocol of the eye bank) were compared among groups using linear mixed model analysis. RESULTS In total, 4185 corneas from 2112 donors were included for analysis. Insulin-dependent diabetic samples with medical complications due to diabetes (N = 231 from 119 donors) showed lower ECD values compared with nondiabetic samples (-102 cells/mm, P = 0.049) and non-insulin-dependent diabetic samples (-117 cells/mm, P = 0.031). ECD values did not differ significantly among the remaining groups. The likelihood of suitability for endothelial transplantation did not differ among all 4 groups. CONCLUSIONS Corneas from donors with insulin-dependent diabetes mellitus and medical complications resulting from the disease have lower mean ECD values compared with other donors. However, our analysis suggests that these corneas are equally likely to be included in the donor pool for corneal transplantation. Additional studies are needed to determine the mechanism(s) contributing to cell loss in donors with advanced diabetes and to assess associated endothelial cell functional impairment.

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 (ATS) and the American College of Chest Physicians (CHEST). Methods A multidisciplinary panel posed six clinical questions in a population, intervention, comparator, outcomes (PICO) format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, confidence in the evidence, certainty about how much the public values the main outcomes, magnitude and balance of desirable and undesirable outcomes, resources and costs associated with the intervention, impact on health disparities, and acceptability and feasibility of the intervention. Results Evidence-based recommendations were formulated and graded initially by subcommittees and then modified following 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.

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.

Background An update of evidence-based guidelines concerning liberation from mechanical ventilation is needed as new evidence has become available. The American College of Chest Physicians (CHEST) and the American Thoracic Society (ATS) have collaborated to provide recommendations to clinicians concerning liberation from the ventilator. Methods Comprehensive evidence syntheses, including meta-analyses, were performed to summarize all available evidence relevant to the guideline panel's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, and the results were summarized in evidence profiles. The evidence syntheses were discussed and recommendations developed and approved by a multidisciplinary committee of experts in mechanical ventilation. Results Recommendations for three population, intervention, comparator, outcome (PICO) questions concerning ventilator liberation are presented in this document. The guideline panel considered the balance of desirable (benefits) and undesirable (burdens, adverse effects, costs) consequences, quality of evidence, feasibility, and acceptability of various interventions with respect to the selected questions. Conditional (weak) recommendations were made to use inspiratory pressure augmentation in the initial spontaneous breathing trial (SBT) and to use protocols to minimize sedation for patients ventilated for more than 24 h. A strong recommendation was made to use preventive noninvasive ventilation (NIV) for high-risk patients ventilated for more than 24 h immediately after extubation to improve selected outcomes. The recommendations were limited by the quality of the available evidence. Conclusions The guideline panel provided recommendations for inspiratory pressure augmentation during an initial SBT, protocols minimizing sedation, and preventative NIV, in relation to ventilator liberation.

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 certaintyintheevidence,andthefeasibilityandacceptabilityofvarious interventions. Recommendations were rated as strong or conditional. Results:Theguidelinepanelmadefourconditionalrecommendations 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.