SAEM systematic online academic resource (SOAR) review: Gastrointestinal illnesses.

Background and Objectives: Free open access medical education (FOAM) has become an essential tool for emergency medicine (EM) education and can be valuable to clinicians as a point-of-care resource. The development of the revised Medical Education Translational Resources Impact and Quality (rMETRIQ) tool provides a standardized means of quality assessment. Previous entries of the Society for Academic Emergency Medicine systematic online academic resource (SOAR) series have focused on renal, endocrine, and sickle cell disorders. In this iteration, we strive to identify, curate, and describe FOAM topics specific to acute gastrointestinal (GI) illnesses. Methods: We searched 389 keywords across 11 GI topics that were modified from the 2019 Model of the Clinical Practice of EM (EM Model) using the search engine Google FOAM and within the top 50 websites listed on Academic Life in Emergency Medicine's Social Media Index. The sites underwent preliminary screening to eliminate resources that were not relevant to EM or GI illnesses. Identified resources were evaluated with the rMETRIQ tool by five board-certified EM physicians who received rMETRIQ tool rater training. Results: After duplicates of the initial 39,505 resources were eliminated, 8059 remained. Primary screening resulted in a final 1202 resources. The most common categories were large bowel (18%), small bowel (13%), stomach (11%), esophagus (11%), biliary (11%), and liver (10%). Many resources covered multiple topics and subtopics. The final mean intraclass correlation coefficient among the five physicians was 0.95 (95% CI 0.92-0.98) for rMETRIQ scoring. We identified 256 sites considered "high quality" with a rMETRIQ score of 16 or higher as designated in prior reviews. Conclusions: This iteration of the SOAR review resulted in the highest number of high-quality resources compared to other SOAR reviews, with 21% of resources thus far scoring ≥ 16. A final list of high-quality resources can guide trainees, educator recommendations, and FOAM authors.

Systematic online academic resource (SOAR) review: Pediatric respiratory infectious disease.

Background: Free open access medical education (FOAM) resources have become increasingly popular in graduate medical education. Despite their accessibility, the assessment of FOAM resources' quality is challenging due to their decentralized nature and the diverse qualifications of their authors and distribution platforms. In this first pediatric systematic online academic resource (SOAR) review, we utilized a systematic methodology to aggregate and assess the quality of FOAM resources on pediatric respiratory infectious disease topics. Methods: We searched 177 keywords using FOAMSearch, the top 50 FOAM websites on the Social Media Index, and seven additional pediatric emergency medicine-focused blogs. Following a basic initial screen, resources then underwent full-text quality assessment utilizing the revised Medical Education Translational Resources: Impact and Quality (rMETRIQ) tool. Results: The search yielded 44,897 resources. After 44,456 were excluded, 441 underwent quality assessment. A total of 36/441 posts (8% of posts) reached the high-quality threshold score (rMETRIQ ≥ 16). The most frequent topics overall were pneumonia and bronchiolitis. A total of 67/441 posts (15% of posts) were found to have a rMETRIQ score of less than or equal to 7, which may indicate poor quality. Conclusions: We systematically identified, described, and performed quality assessment on FOAM resources pertaining to the topic of pediatric respiratory infectious disease. We found that there is a paucity of high-quality posts on this topic. Despite this, the curated list of high-quality resources can help guide trainees and educators toward relevant educational information and suggest unmet needs for future FOAM resources.

Hemorrhage Following Muller's Muscle Conjunctival Resection: Description and Case-Control Study.

PURPOSE: The purpose of this study was to report a series of patients with postoperative hemorrhage after Muller's muscle conjunctival resection surgery and compare risk factors and outcomes with a control population. METHODS: In this case-control study, records of patients who underwent Muller's muscle conjunctival resection over 5 years were reviewed for a history of postoperative hemorrhage occurring >24 hours after surgery. A 4:1 control population was matched for age and sex. Clinical data collected included demographics, medical history, medications, and subsequent surgery. Preoperative and 3-month postoperative marginal reflex distance 1 were measured digitally using ImageJ. The hemorrhage and control groups were compared using Fisher's exact tests for categorical variables and independent samples t tests for continuous variables. RESULTS: The hemorrhage group contained 10 patients (mean age 66.4 ± 18.5 years). The control group consisted of 40 age and sex-matched controls. Of 350 charts reviewed, there were 10 cases of postoperative hemorrhage (incidence 2.9%). Hemorrhage occurred a mean of 4.2 ± 1.3 (range 2-7) days after surgery and lasted for a mean of 29.3 ± 19.1 (range 12-72) hours. In all 10 cases, the bleeding resolved with conservative measures. There was no difference between the hemorrhage and control groups in terms of medical conditions, blood thinners, and surgical revision. Preoperative, postoperative, and change in marginal reflex distance 1 did not differ between the hemorrhage and control groups. CONCLUSIONS: Hemorrhage occurs approximately 4-5 days postoperatively in a small percentage of patients undergoing Muller's muscle conjunctival resection surgery. This investigation did not identify any consistent risk factors, and outcomes in this patient population appear no different than controls.

SARS-CoV-2 spike protein promotes inflammatory cytokine activation and aggravates rheumatoid arthritis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) induces inflammation, autoantibody production, and thrombosis, which are common symptoms of autoimmune diseases, including rheumatoid arthritis (RA). However, the effect of COVID-19 on autoimmune disease is not yet fully understood. METHODS: This study was performed to investigate the effects of COVID-19 on the development and progression of RA using a collagen-induced arthritis (CIA) animal model. Human fibroblast-like synoviocytes (FLS) were transduced with lentivirus carrying the SARS-CoV-2 spike protein gene in vitro, and the levels of inflammatory cytokine and chemokine expression were measured. For in vivo experiments, CIA mice were injected with the gene encoding SARS-CoV-2 spike protein, and disease severity, levels of autoantibodies, thrombotic factors, and inflammatory cytokine and chemokine expression were assessed. In the in vitro experiments, the levels of inflammatory cytokine and chemokine expression were significantly increased by overexpression of SARS-CoV-2 spike protein in human FLS. RESULTS: The incidence and severity of RA in CIA mice were slightly increased by SARS-CoV-2 spike protein in vivo. In addition, the levels of autoantibodies and thrombotic factors, such as anti-CXC chemokine ligand 4 (CXCL4, also called PF4) antibodies and anti-phospholipid antibodies were significantly increased by SARS-CoV-2 spike protein. Furthermore, tissue destruction and inflammatory cytokine level in joint tissue were markedly increased in CIA mice by SARS-CoV-2 spike protein. CONCLUSIONS: The results of the present study suggested that COVID-19 accelerates the development and progression of RA by increasing inflammation, autoantibody production, and thrombosis. Video Abstract.

Henle Fiber Layer Hemorrhage in Macular Telangiectasia Type 2: Is Right Eye Dominance Coincidence or Consequence?

PURPOSE: To summarize all reported cases of Henle fiber layer (HFL) hemorrhage in the absence of subretinal neovascularization (SRNV) in patients with macular telangiectasia type 2 (MacTel2) and to propose a mechanism for the right-sided predominance of this unique presentation. DESIGN: Perspective. METHODS: Collection, review, and analysis of all cases in the literature and in the authors' databases of HFL hemorrhage in MacTel2, including analysis of baseline and follow-up multimodal retinal imaging findings of selected cases. Elucidation of the complex interplay of systemic venous pressure with the deep retinal capillary plexus and hypothesis regarding the right-sided predilection of HFL hemorrhage complicating MacTel2. RESULTS: Ten patients presented with a unilateral, characteristic radial macular hemorrhage within the HFL that affected only the right eye in all cases. Absence of SRNV was confirmed by fluorescein angiography and/or optical coherence tomography angiography. The hemorrhage resolved spontaneously in at least 7 of the 10 eyes. The HFL hemorrhage may plausibly be explained by dysfunction of the deep capillary plexus in MacTel2 combined with an acute rise in central venous pressure, for which the right side may be at increased risk. CONCLUSIONS: HFL hemorrhage can complicate MacTel2 in the absence of SRNV, and the radial pattern of blood affecting only the right eye is remarkable. The right eye predominance may be multifactorial in etiology. Related factors may include the right-sided predilection of MacTel2 and/or increased right-sided dural sinus drainage related to normal anatomical variation.

Systematic online academic resource (SOAR) review: Endocrine, metabolic, and nutritional disorders.

BACKGROUND: Free open-access medical education (FOAM) has become an integral resource for medical school and residency education. However, questions of quality and inconsistent coverage of core topics remain. In this second entry of the SAEM Systematic Online Academic Resource (SOAR) series, we describe the application of a systematic methodology to identify, curate, and describe FOAM topics specific to endocrine, metabolic, and nutritional disorders as defined by the 2016 Model of the Clinical Practice of Emergency Medicine (MCPEM). METHODS: We developed an automated algorithm to search 264 keywords derived from nine subtopics within the MCPEM category in the FOAM Search (a customized FOAM search tool) and the Social Media index. The top 100 results were extracted for each keyword. Resources underwent a manual iterative screening process, and those relevant to endocrine, metabolic, or nutritional disorders and EM were evaluated with the revised Medical Education Translational Resources: Impact and Quality (rMETRIQ) tool. RESULTS: The search yielded 36,346 resources, of which 756 met the criteria for quality assessment. After rMETRIQ tool training, four raters demonstrated an average measured intraclass correlation coefficient of 0.94 (95% confidence interval = 0.88 to 0.97, p < 0.001). A total of 121 posts (16% of posts) covering 25 subtopics were identified as high quality (rMETRIQ ≥16). The most covered subtopic was potassium disorders, representing 15% of all posts. Subtopics that did not have a high-quality resource identified include metabolic alkalosis, respiratory alkalosis, fluid overload, phosphorus metabolism, hyperglycemia, malabsorption, malnutrition, and thyroiditis. From most to least common, the overall target audience was junior resident (91%), PGY-1 resident (88%), senior resident (81%), clerk (64%), attending (50%), and preclerkship (9%). CONCLUSIONS: We systematically identified, described, and curated FOAM resources for EM learners on the topic of endocrine, metabolic, and nutritional disorders. A final list of high-quality resources can guide trainees, educator recommendations, and FOAM authors.

Pentosan Polysulfate Maculopathy: Prevalence, Spectrum of Disease, and Choroidal Imaging Analysis Based on Prospective Screening.

PURPOSE: To describe the prevalence and spectrum of disease of pentosan polysulfate (PPS) maculopathy in a large multimodal retinal imaging study and to report the results of choroidal vascularity index (CVI) analysis. DESIGN: Prospective cohort study Methods: Of 741 patients prescribed PPS within a large university database, 100 (13.4%) with any consumption agreed to participate in a prospective screening investigation. Multimodal retinal imaging including near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) was performed in all patients. Characteristic findings of affected patients were identified, and affected and unaffected cohorts were compared. CVI, defined as stromal choroidal area (SCA) divided by the total choroidal area, was analyzed. RESULTS: The prevalence of PPS maculopathy was 16%. NIR illustrated punctate hyperreflective lesions with early presentation. FAF illustrated a speckled macular network of hypo- and hyperautofluorescence colocalized with multifocal hyperreflective retinal pigment epithelial lesions on SD-OCT. Advanced cases demonstrated varying degrees of atrophy. The affected cohort exhibited significantly greater mean PPS therapy duration, mean daily dosage, and mean cumulative dosage (19.5±5.5 years, 433.9±137.6 mg, 3,103.1±1,402.2 g) compared with the unaffected cohort (7.1±6.6 years, 291.6±177.6 mg, 768.4±754.8 g). SCA was significantly lower and CVI was significantly greater in the affected vs the unaffected group. CONCLUSIONS: This prospective cohort study identified a prevalence of PPS maculopathy of 15%-20% among PPS users who agreed to participate. A spectrum of findings may be observed with multimodal retinal imaging. Significant choroidal abnormalities associated with this characteristic maculopathy may provide surrogate markers of macular toxicity.

Retained gallstones: an elusive complication of laparoscopic cholecystectomy.

A young, healthy woman presented to the emergency department multiple times with right upper quadrant pain and subjective fevers for over a year after her laparoscopic cholecystectomy. The patient required multiple hospital visits and extensive work-ups before finally being diagnosed with retained gallstones in her abdomen. After surgical removal of the stones, her symptoms resolved completely. The case highlights the challenges in diagnosing retained gallstones, the substantial burdens they can impose on patients, and the importance of prevention and thorough documentation.

Safety and Efficacy of Colored Iris Reconstruction Lens Implantation.

PURPOSE: We sought to evaluate the 1- to 9-year safety and efficacy of colored iris reconstruction lens implantation in eyes with visual disturbances caused by partial or complete aniridia. DESIGN: Prospective, interventional case series. METHODS: Thirty-eight patients were implanted with Ophtec 311 colored iris reconstruction lenses at the University of California, Los Angeles as part of a larger U.S. Food and Drug Administration clinical trial. Patients in group 1 lacked corneal pathology. Patients in group 2 patients had corneal pathology, such as endothelial failure, previous transplants, or scarring. Safety measures included loss of corrected distance visual acuity (CDVA), surgical complications, adverse events, secondary interventions, and corneal endothelial cell loss. Efficacy measures included improvement in uncorrected distance visual acuity (UDVA) and subjective visual disturbances. RESULTS: Groups 1 (n = 8) and 2 (n = 30) showed improvements in CDVA (P = .155 and .038), UDVA (P = .002 and P < .001), and subjective visual disturbance scores at year 3. Median CDVA and UDVA declined slightly for both groups after 1-2 years. Group 2 experienced more adverse events, surgical complications, and secondary interventions. Endothelial cell loss was greater for group 2 (19.7%) than group 1 (8.05%), although this difference was not statistically significant (P = .067). CONCLUSIONS: Colored iris reconstruction lens implantation improved CDVA, UDVA, and subjective visual disturbances 3 years postoperatively and beyond. Adverse events, complications, and subsequent declines in visual acuity were common, however, in these eyes with complex medical and surgical histories.

Alterations in GRHL2-OVOL2-ZEB1 axis and aberrant activation of Wnt signaling lead to altered gene transcription in posterior polymorphous corneal dystrophy.

Mutations associated with posterior polymorphous corneal dystrophy (PPCD) have been identified in three genes: ZEB1 (zinc-finger E-box binding homeobox 1) associated with sub-type PPCD3; OVOL2 (ovol-like zinc finger 2) associated with sub-type PPCD1; and GRHL2 (grainyhead like transcription factor 2) associated with sub-type PPCD4. Each of these genes encodes a transcription factor that regulates cell-state transitions. While the discovery of these PPCD-associated genes has greatly expanded our knowledge of the genetic basis of PPCD, the molecular mechanisms via which mutations in these genes lead to indistinguishable disease phenotypes have yet to be elucidated. To characterize the gene expression profiles of the genetic sub-types of PPCD, RNA-seq was performed on corneal endothelium derived from an individual with PPCD1 who harbors a c.-307T > C OVOL2 promoter mutation. Transcriptomic analysis of this and previously-reported RNA-seq data from two individuals with PPCD (the first with PPCD3 associated with a ZEB1 truncating mutation (c.1381delinsGACGAT) and the second with genetically unresolved PPCD in which ZEB1 coding region, OVOL2 promoter and GRHL2 promoter, exon 1, and intron 1 mutations were excluded) revealed: OVOL2 expression increased in PPCD1 (259 fold), unchanged in PPCD3 and slightly increased in genetically unresolved PPCD (from 0 TPM to 0.86 TPM, undefined fold change); ZEB1 expression decreased in PPCD1 (-5.9 fold), PPCD3 (-3.95 fold) and genetically unresolved PPCD (-3.96 fold); and GRHL2 expression increased in PPCD1 (333.5 fold), slightly increased (from 0 TPM to 0.67 TPM, undefined fold change) in PPCD3 and increased in genetically unresolved PPCD (1853 fold). Additionally, as the majority of pedigrees affected with PPCD remain genetically unresolved, we screened the promoter, exon 1, and intron 1 regions of GRHL2 in 24 PPCD probands who do not harbor a ZEB1 or OVOL2 mutation. GRHL2 screening did not identify any novel or rare GRHL2 variant in these 24 individuals. As ZEB1 can act as an activator or repressor of downstream target gene expression depending on Wnt signaling pathway activation or deactivation, we also sought to determine whether or not Wnt signaling is active in PPCD by performing immunohistochemistry in corneal tissue sections derived from an individual affected with PPCD3 and from an individual with genetically unresolved PPCD. Immunohistochemistry results demonstrated corneal endothelial nuclear accumulation of S552 phos-ß-catenin and cytosolic localization of S33/37/T42 non-phosphorylated ß-catenin in PPCD, indicating aberrant activation of Wnt signaling, which was not observed in control corneal endothelium. These findings suggest that alterations in the ZEB1-OVOL2-GRHL2 axis (caused by PPCD-associated mutations) lead to changes in corneal endothelial cell state and molecular pathways, including the aberrant activation of the Wnt signaling pathway.

Hepatoprotective effect of pinoresinol on carbon tetrachloride-induced hepatic damage in mice.

Forsythiae Fructus is known to have diuretic, anti-bacterial, and anti-inflammatory activities. This study examined the hepatoprotective effects of pinoresinol, a lignan isolated from Forsythiae Fructus, against carbon tetrachloride (CCl(4))-induced liver injury. Mice were treated intraperitoneally with vehicle or pinoresinol (25, 50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20 microl/kg) injection. In the vehicle-treated CCl(4 )group, serum aminotransferase activities were significantly increased 24 h after CCl4 injection, and these increases were attenuated by pinoresinol at all doses. Hepatic glutathione contents were significantly decreased and lipid peroxidation was increased after CCl4 treatment. These changes were attenuated by 50 and 100 mg/kg of pinoresinol. The levels of protein and mRNA expression of inflammatory mediators, including tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2, were significantly increased after CCl4 injection; and these increases were attenuated by pinoresinol. Nuclear translocation of nuclear factor-kappaB (NF-kappaB) and phosphorylation of c-Jun, one of the components of activating protein 1 (AP-1), were inhibited by pinoresinol. Our results suggest that pinoresinol ameliorates CCl4)-induced acute liver injury, and this protection is likely due to anti-oxidative activity and down-regulation of inflammatory mediators through inhibition of NF-kappaB and AP-1.

Palmatine attenuates D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice.

Palmatine is an isoquinoline alkaloid from Coptis chinensis, an herbal medicine used to treat various inflammatory diseases such as gastritis, edema and dermatitis. The present study examined the cytoprotective properties of palmatine on d(+)-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were intraperitoneally given GalN (700 mg/kg)/LPS (10 microg/kg). Palmatine (25, 50, 100, and 200mg/kg) was administered 1h before GalN/LPS. GalN/LPS increased the mortality and serum aminotransferase activities. These increases were attenuated by palmatine. GalN/LPS increased hepatic lipid peroxidation and decreased the contents of reduced glutathione. Palmatine did not affect the lipid peroxidation and glutathione content. GalN/LPS increased the circulating levels of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and IL-10. Palmatine prevented the increase of serum TNF-alpha and augmented that of serum IL-10. GalN/LPS treatment also increased the levels of TNF-alpha, IL-6 and IL-10 mRNA expression in liver tissue. Palmatine decreased the TNF-alpha mRNA expression and increased the IL-10 mRNA expression. Palmatine attenuated the apoptosis of hepatocytes, as evidenced by the TUNEL method and capase-3 analysis. Our data suggest that palmatine alleviates GalN/LPS-induced liver injury by modulating the cytokine response and inhibiting apoptosis.

The roles of Kupffer cells in hepatic dysfunction induced by ischemia/reperfusion in rats.

This study examined the role of Kupffer cells in altering the hepatic secretory and microsomal function during ischemia and reperfusion (Is/Rp). Rats were subjected to 60 min of hepatic ischemia, followed by 1 and 5 h of reperfusion. Gadolinium chloride (GdCl3, 7.5 mg/kg body weight, intravenously) was used to inactivate the Kupffer cells 1 day prior to ischemia. Is/Rp markedly increased the serum aminotransferase level and the extent of lipid peroxidation. GdCl3 significantly attenuated these increases. Is/Rp markedly decreased the bile flow and cholate output, and GdCl3 restored their secretion. The cytochrome P450 content was decreased by Is/Rp. However, these decreases were not prevented by GdCl3. The aminopyrine N-demethylase activity was decreased by Is/Rp, while the aniline p-hydroxylase activity was increased. GdCl3 prevented the increase in the aniline p-hydroxylase activity. Overall, Is/Rp diminishes the hepatic secretory and microsomal drug-metabolizing functions, and Kupffer cells are involved in this hepatobiliary dysfunction.