Intra-Observer and Inter-Observer Variability of Intraocular Lens Measurements Using an Interferometry Metrology Device.

The NIMO TEMPO (Lambda-X, Nivelles, Belgium) is a novel, user-friendly and compact device designed for in vitro optical analysis of refractive and diffractive intraocular lenses (IOLs). This device analyzes the IOL wavefront and generates a synthetic eye model for numerical computation. The objective of this study was to evaluate the precision of this innovative device. Intra- and inter-observer variability were calculated using a two-way analysis of variance (ANOVA) after conducting ten measurements of eight different IOL models, with each measurement being repeated by three distinct operators (resulting in a total of 30 measurements for each IOL). The device demonstrated satisfactory intra- and inter-observer variability in evaluating IOL power and modulation transfer function (MTF) profiles, with values of 0.066 and 0.078 diopters for IOL power and 0.018 and 0.019 for MTF measurements, respectively. Furthermore, this hybrid optical and numerical in vitro IOL wavefront analyzer appears to have several advantages over conventional optical bench devices. It reduces the need for operator manipulation, and allows for numerical modeling of various optical environments, including cornea models and apertures. In conclusion, this novel metrology device designed for refractive and diffractive IOLs appears to provide a satisfactory precision, making it a promising tool in the field of IOL metrology.

Paper waste from instructions for use brochures in cataract surgery implant packaging in Europe and the United States.

PURPOSE: To assess the extent of paper waste generated per year by instructions for use (IFUs) brochures included in intraocular lens (IOL) packaging in Europe and the U.S. SETTING: Rothschild Foundation Hospital, Paris, France; Royal Free London NHS Foundation Trust; Center for Sight, London, United Kingdom. DESIGN: Experimental study. METHODS: A sample of IOLs were collected and each IFU was weighed. In addition, the cumulative weight of these brochures used in cataract surgeries performed annually in Europe and the U.S. was estimated, and the potential annual paper conservation that could be achieved if all manufacturers adopted electronic IFUs (e-IFUs) in Europe and the U.S. was determined. RESULTS: The mean and standard deviation of the weight for overall IFUs, classic IFUs, and e-IFUs were 17.6 ± 13.8 g, 23.5 ± 13.2 g, and 2.9 ± 1.9 g, respectively. The estimated cumulative weight of paper generated from the IFUs accompanying implants used in European and U.S. cataract surgeries is 153 tons. If all manufacturers transition to e-IFUs, the cumulative weight saved would be 128 tons (-84%), equivalent to 120 tons of carbon dioxide equivalent and the preservation of more than 2000 trees annually. CONCLUSIONS: The classic IFUs in IOL packaging result in a significant amount of paper waste annually. Therefore, there is an urgent need for a rapid transition to e-IFU technology. The adoption of e-IFUs has already been authorized in Europe and the U.S., and it is crucial to expedite this process.

Effect of mydriasis on chord mu value in cataract surgery candidates.

PURPOSE: This study investigates the relationship between pupil size during biometry examinations and the chord mu value in candidates for cataract surgery. METHODS: Retrospective analysis of ocular biometry measurements was performed on consecutive cataract surgery candidates above 50 years of age, examined between 2018 and 2020 at a single tertiary referral center. Statistical analysis assessed the association between pupil size and the chord mu value. The population was categorized into groups based on pupil size, and an analysis was conducted on the barycenter positions of the iris and pupil center for each group. RESULTS: The analysis included 2877 patients. A weak positive correlation was observed between the chord mu value and pupil size using Pearson's test (r = 0.160, p < 0.01). Group stratification by pupil size indicated temporal and inferior shifts in pupil center barycenter as pupil size increased, reflecting asymmetrical pupil dilation during mydriasis. A moderate positive correlation between the chord mu value and chord alpha value was identified (Pearson's test, r = 0.641, p < 0.01). As expected, no correlation was found between chord alpha value and pupil size. CONCLUSIONS: Chord mu values were higher in patients with mydriatic pupils, likely due to asymmetric pupil dilation and center displacement. Evaluating chord mu values requires considering pupil status and conducting biometry under standardized lighting to prevent misinterpretation caused by pharmacological dilation. This caution is crucial to avoid erroneously excluding eligible patients from multifocal IOL implants. Alternatively, the chord alpha value could serve as a more appropriate alternative in such scenarios.

How Advancement in Bone Science Should Inform the Examination and Treatment of Femoral Shaft Bone Stress Injuries in Running Athletes.

Stress fractures likely have a 1-2% incidence in athletes in general. In runners, a more vulnerable population, incidence rates likely range between 3.2 and 21% with female runners having greater susceptibility. The incidence of femoral shaft stress fractures is less well known. New basic and translational science research may impact the way clinicians diagnose and treat femoral stress fractures. By using a fictitious case study, this paper applies bone science to suggest new approaches to evaluating and treating femoral shaft stress fractures in the running population.

Individualized Exercise Prescription for Athletes Using a Construct-Based Model.

Rehabilitation professionals prescribe exercise regularly with the goals of decreasing pain, increasing function, and returning athletes to competition. To maximize the effect of an exercise intervention, the program must be individualized and in context for the athlete considering biopsychosocial aspects of care. Current models of exercise prescription may not be ideal considering that less than 50% of injured athletes return to their pre-injury level. Advice on exercise prescription has been offered in the past, but the paradigms are either not user friendly or user friendly but linear, based on phases of recovery. As such, there is a need for a more flexible exercise prescription paradigm that should improve the individuality of exercise prescription. In this Current Opinion, we offer a user-friendly construct-oriented paradigm designed to facilitate the creation of individualized exercise programs for athletes.

Analysis of Psilocybin-Assisted Therapy in Medicine: A Narrative Review.

Psilocybin-containing mushrooms have been consumed by various cultures in many different parts of the world for thousands of years. Psilocybin, a classic psychedelic, contains unique psychoactive properties and has been incorporated into religious ceremonies and investigated for its medicinal value. In the mid-20th century, psilocybin, along with most other classic psychedelics (5HT-2A agonists), was classified as a Schedule I substance, bringing a halt to research on its medicinal utility. The resurgence of clinical trials involving psilocybin in the 21st century has produced promising results concerning the treatment of addiction, depression, and end-of-life mood disorders. Results from these trials have shown significant reductions in depression and anxiety when compared with a placebo, and one trial found no significant difference when compared to a routinely prescribed selective serotonin reuptake inhibitor (SSRI). Studies conducted with patients with advanced-stage cancer have demonstrated that psilocybin may also be beneficial at reducing depression and anxiety associated with psychological crises due to a terminal diagnosis. Psilocybin therapy in the treatment of addiction, which is notoriously difficult to treat, has shown encouraging results. Due to its low toxicity and low risk of overuse, psilocybin has the potential to have a significant influence in the field of addiction medicine. Psilocybin addiction research has been primarily focused on nicotine and alcohol and, in a few small, open-label trials, has shown superiority over traditional therapies. Psilocybin has a relatively unique and incompletely understood mechanism of action, which allows it to be given at several isolated periods. This infrequent dosing regimen has been shown to produce durable effects with minimal toxicity. This review analyzes the potential of psilocybin in the treatment of addiction, depression, and end-of-life mood disorders. In addition, it will discuss the difficulties involved with conducting scientific research on psychedelic compounds, adverse effects, and the therapeutic measures that are necessary to accompany the safe and effective administration of these psychoactive chemicals.

NASHFit: A randomized controlled trial of an exercise training program to reduce clotting risk in patients with NASH.

BACKGROUND AND AIMS: NASH is a common disease associated with increased rates of thromboembolism (TE). Although exercise training can lessen thrombotic risk in patients with vascular disease, whether similar findings are observed in patients with NASH is open for study. APPROACH AND RESULTS: We conducted a 20-week randomized controlled clinical trial involving patients with biopsy-confirmed NASH. Patients were randomly assigned (2:1 ratio) to receive either an exercise training program or standard clinical care. The primary endpoint was change in plasminogen activator inhibitor 1 (PAI-1) level, an established thrombotic biomarker. Twenty-eight patients were randomly assigned (18 exercise training and 10 standard clinical care). PAI-1 level was significantly decreased by exercise training when compared to standard clinical care (-40 ± 100 vs. +70 ± 63 ng/ml; p = 0.02). Exercise training decreased MRI proton density fat fraction (MRI-PDFF; -4.7 ± 5.6 vs. 1.2 ± 2.8% absolute liver fat; p = 0.01); 40% of exercise subjects had a ≥30% relative reduction in MRI-PDFF (histological response threshold) compared to 13% for standard of care (p < 0.01). Exercise training improved fitness (VO2 peak, +3.0 ± 5.6 vs. -1.8 ± 5.1 ml/kg/min; p = 0.05) in comparison to standard clinical care. CONCLUSIONS: This clinical trial showed that, independent of weight loss or dietary change, exercise training resulted in a significantly greater decrease in thrombotic risk than standard clinical care in patients with NASH, in parallel with MRI-PDFF reduction and improvement in fitness. Future studies are required to determine whether exercise training can directly impact patient outcomes and lower rates of TE.

Initial endoscopic intervention is not associated with reduced risk of recurrent gastrointestinal bleeding in left ventricular assist device patients.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used for mechanical support of end-stage heart failure. Gastrointestinal bleeding (GIB) confers a significant morbidity in LVAD patients, with rates of up to 30% at 5 years. We assessed predictors of index and recurrent GIB (rGIB) in LVAD patients to risk stratify patients and evaluate if endoscopic approach and intervention at index GIB impacted rGIB. METHODS: A retrospective chart review of all LVAD patients at our institution from 01/01/2006 to 31/10/2016 was completed. Predictors for index and recurrent GIB were analyzed. Multivariate logistic regression analysis was created using only statistically significant dependent variables and adjusted for demographic variables. RESULTS: A total of 77/214 (36%) patients developed GIB, and 38/214 (17.8%) developed rGIB. Destination therapy (P=0.01), longer duration of LVAD (P=0.03), and low albumin (<3.5 g/dL) (P<0.001) were associated with increased risk of index GIB. Charlson Comorbidity Index, heart failure etiology, and Medicare were predictors of index GIB on univariate analysis, but this was not seen on multivariate analysis. Performing an endoscopy with/without intervention, non- angioectasia lesions, and location of bleeding were not statistically significant predictors of rGIB. Longer duration of hospitalization appeared to be protective for rGIB on univariate analysis. CONCLUSIONS: Index endoscopy and intervention is not associated with reduced risk of rGIB in LVAD patients. Several independent factors are associated with the risk of index GIB. Albumin is a potentially modifiable risk factor, and likely contributes to bleeding through poor nutrition. It is a surrogate marker for systemic illness, and may have pharmacologic implications.

Utilization of a Directly Supervised Telehealth-Based Exercise Training Program in Patients With Nonalcoholic Steatohepatitis: Feasibility Study.

BACKGROUND: Most patients with nonalcoholic fatty liver disease (NAFLD) are physically inactive despite the well-known benefits of physical activity. Telehealth offers promise as a novel way to deliver an exercise training program and increase physical activity. However, the feasibility, safety, and efficacy of telehealth-based exercise programs is unknown in patients with NAFLD. OBJECTIVE: The aim of this study was to determine the feasibility of a directly supervised exercise training program delivered exclusively with telehealth to patients with nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD. METHODS: In response to COVID-19 research restrictions, we adapted an existing clinical trial and delivered 20 weeks of moderate-intensity aerobic training 5 days a week under real-time direct supervision using an audio-visual telehealth platform. Aerobic training was completed by walking outdoors or using a home treadmill. Fitness activity trackers with heart rate monitors ensured exercise was completed at the prescribed intensity with real-time feedback from an exercise physiologist. RESULTS: Three female patients with biopsy-proven NASH were enrolled with a mean age of 52 (SD 14) years. The mean body mass index was 31.9 (SD 5.1) kg/m2. All patients had metabolic syndrome. All patients completed over 80% of exercise sessions (mean 84% [SD 3%]) and no adverse events occurred. Body weight (mean -5.1% [SD 3.7%]), body fat (mean -4.4% [SD 2.3%]), and waist circumference (mean -1.3 in. [SD 1.6 in.]) all improved with exercise. The mean relative reduction in magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was 35.1% (SD 8.8%). Mean reductions in hemoglobin A1c and Homeostatic Model Assessment for Insulin Resistance were also observed (-0.5% [SD 0.2%] and -4.0 [SD 1.2], respectively). The mean peak oxygen consumption (VO2peak) improved by 9.9 (SD 6.6) mL/kg/min. CONCLUSIONS: This proof-of-concept study found that supervised exercise training delivered via telehealth is feasible and safe in patients with NASH. Telehealth-based exercise training also appears to be highly efficacious in patients with NASH, but this will need to be confirmed by future large-scale trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT03518294; https://clinicaltrials.gov/ct2/show/NCT03518294.

Lactulose-induced pneumatosis intestinalis following colonoscopy: a case report.

Pneumatosis intestinalis (PI) occurs when gas is discovered in the intestinal wall and is categorized into two types: primary PI which is idiopathic and mainly occurs in the colon, and secondary PI which occurs more often in the small bowel but has variable presentation and etiology. We report a case of a patient status post-orthotopic deceased liver transplantation complicated by a portal vein thrombus on chronic lactulose for portosystemic encephalopathy who presented due to pyelonephritis and persistent diarrhea. The patient underwent colonoscopy with random biopsies and subsequently developed acute sepsis with Escherichia coli bacteremia. The findings of PI were noted on computed tomography imaging obtained 5 days post-colonoscopy, due to persistent post-procedure abdominal pain. The patient was treated with discontinuation of lactulose, supportive care, and antibiotics for her bacteremia with resolution of her PI 3 days later. This suggests that a combination of factors may lead to the development of PI, and while some cases require emergent intervention including surgery, others may be treated conservatively. Awareness of risk factors that may precipitate PI and specific clinical predictors may help to both mitigate and manage PI appropriately.

State dependence: Does a prior injury predict a future injury?

The sports medicine literature is filled with associations between injury and causal factors. However, those results have been inconsistent. We're left wondering which of our athletes might need more attention and where our efforts might be best spent. Resistance to injury is the result of interaction between many variables. These variables are interdependent with dynamic relationships which can be sometimes correlated, at times anti-correlated and from time to time show no relationship with injury risk. Relationships we may have seen yesterday do not necessarily hold true for today and we should not use those to infer what will happen. This perspective piece builds on prior works and describes how the complex interaction between injury determinants presents in other systems, why determinants are not stable and instead vary over time due to internal and external forcing and why our prediction ability remains limited even when determinants are identified. Patterns built from frequent time series data in conjunction with nonlinear dynamical methods can offer us a new approach to thinking about injury prediction.

Rhizosphere activity in an old-growth forest reacts rapidly to changes in soil moisture and shapes whole-tree carbon allocation.

Drought alters carbon (C) allocation within trees, thereby impairing tree growth. Recovery of root and leaf functioning and prioritized C supply to sink tissues after drought may compensate for drought-induced reduction of assimilation and growth. It remains unclear if C allocation to sink tissues during and following drought is controlled by altered sink metabolic activities or by the availability of new assimilates. Understanding such mechanisms is required to predict forests' resilience to a changing climate. We investigated the impact of drought and drought release on C allocation in a 100-y-old Scots pine forest. We applied 13CO2 pulse labeling to naturally dry control and long-term irrigated trees and tracked the fate of the label in above- and belowground C pools and fluxes. Allocation of new assimilates belowground was ca. 53% lower under nonirrigated conditions. A short rainfall event, which led to a temporary increase in the soil water content (SWC) in the topsoil, strongly increased the amounts of C transported belowground in the nonirrigated plots to values comparable to those in the irrigated plots. This switch in allocation patterns was congruent with a tipping point at around 15% SWC in the response of the respiratory activity of soil microbes. These results indicate that the metabolic sink activity in the rhizosphere and its modulation by soil moisture can drive C allocation within adult trees and ecosystems. Even a subtle increase in soil moisture can lead to a rapid recovery of belowground functions that in turn affects the direction of C transport in trees.

A Novel Method of Visual Field Assessment for Patients with Unilateral Severely Limited Central Vision: A Pilot Study.

PURPOSE: Reliable visual field testing requires the tested eye to be fixated on a central target. This poses a major obstacle for eyes with severe central vision loss. This pilot study assesses whether it may be feasible to examine such patients with a modified method. METHODS: A green filter was placed over the fellow eye. A FASTPAC algorithm was used with a red stimulus. The green filter prevented transmission of the red stimuli but allowed visualization of the yellow fixation light. Subjects were tested by both the conventional and the novel method, performed in a randomized order. We compared the reliability indices and also the precision of the two methods. RESULTS: We present results from six patients. The novel method was associated with an 85% reduction in fixation losses (P=0.028) and a 58% reduction in eye motion on gaze tracking (P=0.007). Further, specialized testing in one of the volunteers demonstrated that the novel technique could more precisely define a small zone of preserved peripheral vision (P=0.008). CONCLUSION: The results of this pilot study suggest that the novel method described may be a feasible strategy for visual field testing in patients with unilateral severe central vision loss.

Correction to: Incorporating Colorectal Cancer Genetic Risk Assessment into Gastroenterology Practice.

The original article unfortunately contained a mistake. On page 8, Table 2, the row with "POLE POLD1" has been shifted right so all the columns are not correct.

Incorporating Colorectal Cancer Genetic Risk Assessment into Gastroenterology Practice.

PURPOSE OF REVIEW: Decades have passed since the underlying molecular etiologies of the most common hereditary forms of colorectal cancer (CRC), Lynch syndrome, and familial adenomatous polyposis (FAP) were first described. With the advent of next-generation sequencing (NGS) panels, the landscape of hereditary CRC testing has changed dramatically. We review available screening strategies, novel CRC predisposition genes, and challenges and opportunities in this field. RECENT FINDINGS: Improved sensitivity and availability of NGS panel testing have greatly expanded our understanding regarding the number of CRC syndromes and their phenotypic expression. A variety of screening strategies are available to identify heritable CRC syndromes, potentially decreasing morbidity and mortality in this population. However, these screening strategies remain imperfect and present challenges regarding their implementation in clinical practice. Screening strategies include universal screening of CRC tumors for Lynch syndrome, clinical prediction algorithms, and risk assessment questionnaires. Additionally, there remains a gap in our understanding of the clinical implications of novel gene mutations of variable penetrance and unexpected NGS panel test results. Incorporation of single nucleotide polymorphisms (SNPs) may help to further refine cancer risk assessment, and the clinical introduction of RNA analysis may allow us to clarify variants of unknown significance (VUSs) and identify deep intronic mutations that would otherwise be missed. Recognition of genetic predisposition to CRC is critical for the practicing gastroenterologist. The evolving field of cancer genetics offers great challenges and opportunities for improved CRC management.

Transluminal washout and debridement of extraluminal contamination as an adjunct to endoscopic defect repair.

BACKGROUND AND AIMS: GI tract perforations and anastomotic dehiscence are increasingly effectively being repaired endoscopically; however, well-known and long-held surgical principles must still be honored. One important principle is that significant extraluminal contamination must be washed out, debrided, and drained in conjunction with repair of the defect if the wound is to effectively heal and resolve. Here we describe the use of endoscopic washout and debridement of extraluminal contamination at the time of luminal defect closure in a 7-patient series at our institution, with video demonstration of 2 patients in the series. METHODS: We reviewed a series of 7 patients at our institution and provide a video demonstration of the described technique in 2 patients. A 50-year-old man with decompensated liver cirrhosis presented with a large distal esophageal disruption secondary to a severe Minnesota tube injury. Extensive thoracic and mediastinal contamination of solid and liquid debris was removed and washed out endoscopically, followed by esophageal defect repair. Closure of the defect with overlapping, fully covered, esophageal stents sutured in place was successful after attempts at repairing the primary disruption with suturing alone failed. A 49-year-old man with multiple endocrine neoplasia type 1 and multiple prior surgeries presented with an acute abdomen and sepsis secondary to a fully perforated duodenal ulcer. Extensive endoscopic washout and lavage of the purulent liquid and semiliquid debris covering the liver, stomach, and adjacent structures was performed, followed by closure of the perforation by endoscopic suturing. A percutaneous pigtailed drainage catheter was placed in the extraluminal cavity to facilitate postoperative drainage, followed by placement of a PEG with jejunal extension for enteric exclusion and nutrition. RESULTS: The results for all 7 patients were reviewed. The overall rate of technical success, defined as effective repair of the luminal defect and drainage of extraluminal contamination, was 100%. The overall rate of clinical success, defined as clinical recovery and return to the patient's previous state of health, was 86% because 1 patient died because of severe concomitant disease. The length of time from the described procedure to hospital discharge ranged from 8 to 52 days (mean, 27 days). CONCLUSION: Endoscopic washout and debridement can effectively and immediately address extraluminal contamination at the time of endoscopic luminal defect repair in appropriately selected patients. Therefore, it may represent a valuable option to address this clinical situation when a more conventional surgical approach is problematic. A more structured study should be considered for the development and validation of this approach.

Influences and Impact of Anxiety and Depression in the Setting of Inflammatory Bowel Disease.

Background: Individuals with inflammatory bowel disease (IBD) are at increased risk of developing anxiety or depression (A&D). Crohn's disease (CD) and ulcerative colitis (UC) with comorbid A&D are both more challenging to manage. IBD providers need to better understand the causes and impact of A&D in order to improve care for IBD patients. We sought to identify clinical factors that influence development of A&D and healthcare utilization in IBD. Methods: This is a retrospective analysis using an IBD natural history registry from a single tertiary care referral center. Presence of A&D was determined based upon responses to the Hospital Anxiety and Depression Scale. Demographic and clinical factors were abstracted to evaluate for significant associations. Results: Four hundred thirty-two IBD patients (132 UC, 256 CD, and 44 indeterminate colitis) were included in this study. One hundred ninety-two (44.4%) had anxiety or depression or both, and most were female (59.4%, P < 0.05). History of surgery (P < 0.05), female gender (P < 0.05), smoking (P < 0.05), and extra-intestinal manifestations (P < 0.01) were each independently predictive of A&D. Inflammatory bowel disease patients with A&D more often underwent imaging studies (53.6% vs 36.7%, P < 0.05), visited the ED (30.7% vs 20.8%, P < 0.05), or were hospitalized (31.7% vs 21.7%, P < 0.05). They were also more frequently prescribed corticosteroids (50.5% vs 36.7%, P < 0.01) and biologic medications (62.5% vs 51.3%, P < 0.05). Finally, they were more likely to have had at least 1 "no-show" (29.2% vs 16.7%, P < 0.01) and had a higher mean number of "no-shows" (0.69 +/- 0.1 vs 0.30 +/- 0.1, P < 0.01) over the study period. Discussion: Anxiety and depression are common in the setting of IBD and are strongly associated with surgical history, disease complications (including extra-intestinal manifestations), smoking, and female gender. Inflammatory bowel disease patients with A&D are also more likely to require therapy and to utilize healthcare resources. This study refines our understanding of A&D development and its impact in IBD and provides additional considerations for management in this setting.

Predictors of 30-Day Mortality in Hospitalized Patients with Clostridium difficile Infection.

OBJECTIVES: Clostridium difficile infection (CDI) is a significant cause of morbidity and mortality and is the most common nosocomial infection in the United States, with associated annual costs of approximately $3 billion. The epidemiology of CDI has changed with the identification of novel risk factors for incident and recurrent CDI. The aim of this study was to identify the predictors of 30-day mortality in hospitalized patients with CDI. METHODS: We identified all of the patients diagnosed as having CDI from January 2011 to December 2014 at our university-setting hospital. Data were extracted using electronic medical records and chart review. The data of all of the patients who died within 30 days of incident CDI were compared with those who survived beyond 30 days of incident CDI. A multivariable logistic regression model was created for mortality after finding a subset of significant predictor variables by making bivariate comparisons also using logistic regression. RESULTS: A total of 893 patients were diagnosed as having CDI during the study period. The mean age was 62 years and 49.5% were women. The mean length of hospital stay was 11.73 days. Of the 893 patients with CDI, 98 (10.97%) died within 30 days of incident CDI. CDI recurrence was noted in 76 patients (8.51%). On multivariate logistic regression analysis, peptic ulcer disease, advanced age, Charlson comorbidity index, and intensive care unit status were found to be significantly associated with 30-day mortality. There was no significant association between acid suppression and CDI mortality. CONCLUSIONS: Advanced age, Charlson comorbidity index, intensive care unit status, and peptic ulcer disease are predictors of all-cause 30-day mortality in hospitalized patients with CDI.