Mammalian RNAi represses pericentromeric lncRNAs to maintain genome stability.

Mammalian pericentromeric tandem repeats produce long noncoding RNAs (lncRNAs) that are dysregulated in cancer and linked to genomic instability. Identifying the basic molecular characteristics of these lncRNAs and their regulation is important to understanding their biological function. Here, we determine that the Argonaute (Ago) proteins of the RNA interference (RNAi) pathway directly and uniformly repress bidirectional pericentromeric lncRNAs in a Dicer-dependent manner in mouse embryonic and adult stem cells. Ago-dependent and Dicer-dependent autoregulatory small RNAs were identified within pericentromeric lncRNA degradation intermediates. We develop an RNase H cleavage assay to determine the relative proportions and lengths of the pericentromeric lncRNA targets. We find that 5'-phosphate and non-polyadenylated bidirectional pericentromeric lncRNAs are expressed at similar proportions. These lncRNAs can span up to 9 repeats, with transcription from the reverse strand template yielding the longer products. Using pericentromeric repeat RNA reporters, we determine that Ago represses pericentromeric lncRNAs after S phase transcription. Upon loss of Ago, pericentromeric lncRNA dysregulation results in delayed cell cycle progression, a defective mitotic spindle assembly checkpoint (SAC) and genomic instability. These results show that an evolutionarily conserved Ago activity at pericentromeres contributes to mammalian genome stability.

Pediatric foot fractures on radiographs: distribution and predictors of surgery.

PURPOSE: To examine the distribution and characteristics of pediatric foot fractures on radiographs with respect to age and skeletal maturation, and to identify predictors of surgery. METHODS: This retrospective study included children (≤ 18 years) with foot fractures, who underwent radiographic examinations (2020-2022). Electronic medical records were reviewed to obtain demographic and clinical data. Fracture characteristics, including anatomic location, presence of displacement, angulation, articular involvement, and, if skeletally immature, physeal involvement and Salter-Harris fracture pattern were collected. Logistic regression models were used to identify predictors of surgery. RESULTS: 1,090 (596-boys, 494-girls; mean age, 11.0 ± 4.0 years) patients with 1,325 (59.8% metatarsal, 33.8% phalangeal, and 6.4% tarsal) fractures were included. Fractures of 1st metatarsal were more common among younger children whereas fractures of 2nd-4th and 5th metatarsals were more common among older children (median ages: 5.9 years vs. 10.3 years and 12.4 years, p < 0.001). Intra-articular fractures were more common among maturing and mature than immature bones (25.3% and 20.4% vs. 9.9%, p < 0.001). Physeal involvement was uncommon (162/977, 16.6%) and the most common pattern was Salter-Harris type II (133/162, 82.1%). A minority (47/1090, 4.3%) of patients required surgery and independent predictors of surgery included physeal involvement (OR = 5.12, 95% CI: 2.48-10.39, p < 0.001), multiple fractures (OR = 3.85, 95% CI: 1.67-8.53, p = 0.001), fracture displacement (OR = 9.16, 95% CI:4.43-19.07, p < 0.001), and articular involvement (OR = 2.72, 95% CI:1.27-5.72, p = 0.008). Using these predictors, the likelihood for surgery ranged between 8.0% with 1 and 86.7% with 3 predictors. CONCLUSION: Pediatric foot fracture patterns differed based on age and regional skeletal maturation. Physeal involvement, multiple fractures, fracture displacement, and articular involvement were independent predictors of surgery in our study group.

Patellar osteochondritis dissecans: maturation-dependent patellofemoral joint characteristics.

BACKGROUND: The likelihood of healing of osteochondritis dissecans decreases with skeletal maturity and there are theories that abnormal biomechanical forces contribute to the development and progression of these lesions. OBJECTIVE: To characterize, according to regional skeletal maturity, the morphology and alignment indices of the patellofemoral joint on MRI in patients with patellar osteochondritis dissecans. MATERIALS AND METHODS: MRI examinations of patients with patellar osteochondritis dissecans obtained between January 2008 and May 2023 were retrospectively reviewed to determine regional skeletal maturity, osteochondritis dissecans lesion size and location, patellar and trochlear morphology (Wiberg/Dejour classifications), and to calculate trochlear sulcus angles, trochlear depth index, lateral trochlear inclination, Insall-Salvati index, Caton-Deschamps index, patellar tendon-lateral trochlear ridge, and tibial tubercle-trochlear groove distances. Values were compared between skeletally immature and mature groups. RESULTS: Sixty-eight children (22 girls, 46 boys, age: 14.0 ± 1.7 years) yielded 74 knees with patellar osteochondritis dissecans lesions, 14 (19%) of which were skeletally mature. The most common anatomic location was over the central patella [median ridge (34/74 - 46%) on the axial images and over the middle third (45/74 - 61%) on the sagittal images]. Overall, mean trochlear sulcus angle (high, 151 ± 11°), trochlear depth index (low, 2.8 ± 1.4 mm), and Insall-Salvati index (borderline, 1.3 ± 0.1) were abnormal for the entire sample. Skeletally mature knees were significantly more likely to have higher (more dysplastic) Dejour types when compared to skeletally immature knees (p < 0.01). Knees in the mature group, compared to immature, had significantly more abnormal mean lateral trochlear inclination (15 ± 8° vs. 19 ± 6°, p = 0.03) and patellar tendon-lateral trochlear ridge distance (5.55 ± 4.31 mm vs. 2.89 ± 4.69 mm, p = 0.04). Half of the knees had ≥ 4 abnormal features that predispose to patellofemoral maltracking; mature knees were significantly (p = 0.02) more likely to have a higher number of abnormal features (> 6 features, 7/14, 50.0%) versus immature knees (0-3 features, 33/60, 55.0%). CONCLUSION: In children with patellar osteochondritis dissecans, abnormal patellofemoral morphology and alignment indices were common in all patients and more severe in mature knees.

Return to Play in Youth Athletes: Role of the Radiologist with Focus on the Upper Extremity.

Increase in youth sports participation, longer duration of play, and earlier starting points have increased the prevalence of acute and repetitive overuse musculoskeletal injuries. This rise in injury rates has led to increased efforts to better understand the susceptible sites of injury that are unique to the growing immature skeleton. Upper extremity injuries are currently the best studied, particularly those that occur among pediatric baseball players and gymnasts. The weak link in skeletally immature athletes is the growth plate complex that includes those injuries located at the epiphyseal and apophyseal primary physes and the peripherally located secondary physes. This article reviews the anatomy and function of these growth plate complexes, followed by a discussion of the pathophysiologic mechanisms, spectrum of imaging findings, and existing evidence-based guidelines for injury prevention and return to play.

Distribution of bacterial community structures and spread of antibiotic resistome at industrially polluted sites of Mini River, Vadodara, Gujarat, India.

The influence of anthropogenic pollution on the distribution of bacterial diversity, antibiotic-resistant bacteria (ARBs), and antibiotic resistance genes (ARGs) was mapped at various geo-tagged sites of Mini River, Vadodara, Gujarat, India. The high-throughput 16S rRNA gene amplicon sequencing analysis revealed a higher relative abundance of Planctomycetota at the polluted sites, compared to the pristine site. Moreover, the relative abundance of Actinobacteriota increased, whereas Chloroflexi decreased in the water samples of polluted sites than the pristine site. The annotation of functional genes in the metagenome samples of Mini River sites indicated the presence of genes involved in the defence mechanisms against bacitracin, aminoglycosides, cephalosporins, chloramphenicol, streptogramin, streptomycin, methicillin, and colicin. The analysis of antibiotic resistome at the polluted sites of Mini River revealed the abundance of sulfonamide, beta-lactam, and aminoglycoside resistance. The presence of pathogens and ARB was significantly higher in water and sediment samples of polluted sites compared to the pristine site. The highest resistance of bacterial populations in the Mini River was recorded against sulfonamide (≥ 7.943 × 103 CFU/mL) and ampicillin (≥ 8.128 × 103 CFU/mL). The real-time PCR-based quantification of ARGs revealed the highest abundance of sulfonamide resistance genes sul1 and sul2 at the polluted sites of the Mini River. Additionally, the antimicrobial resistance genes aac(6')-Ib-Cr and blaTEM were also found abundantly at polluted sites of the Mini River. The findings provide insights into how anthropogenic pollution drives the ARG and ARB distribution in the riverine ecosystem, which may help with the development of antimicrobial resistance mitigation strategies.

Identification of fractures on pediatric foot radiographs: do localization cues improve diagnostic accuracy and reduce interpretation time?

OBJECTIVE: To investigate the diagnostic accuracy and time in the detection of fractures on pediatric foot radiographs marked without and with localization cues. METHOD: One-hundred randomly selected foot radiographic examinations that were performed on children (<18 years old) after injury and with at least 4 weeks of follow-up were included. Blinded to history and diagnosis, 4 readers (one each: medical student, pediatrician, pediatric orthopedic surgeon, and pediatric musculoskeletal radiologist) retrospectively and independently reviewed each examination twice (without and with cue, at least 1 month apart, and after randomization). Each reader recorded the presence or absence of a fracture, fracture location, diagnostic confidence, and the total (interpretation) time spent on each study. Diagnostic accuracy, reader confidence, and interpretation time were compared between examinations without and with cues. RESULTS: Our study included 59 examinations without and 41 with fractures (21 phalangeal, 18 metatarsal, and 2 tarsal fractures). Localization cues improved inter-reader agreement (κ=0.36 to 0.64), overall sensitivity (68 to 72%), specificity (66 to 73%), and diagnostic accuracy (67 to 73%); thus, overcalled and missed rates also improved from 34 to 27% and 32 to 28%, respectively. Reader confidence improved with cue (49 to 61%, p<0.01) with higher incremental improvement with younger children (30% for 1-6 years; 14% for 7-11 years; and 10% for 12-17 years). Interpretation time decreased by 40% per examination (40±22 s without to 24±13 s with cues, p<0.001). CONCLUSION: Localization cues improved diagnostic accuracy and reader confidence, reducing interpretation time in the detection of pediatric foot fractures.

Pediatric thrower's elbow: maturation-dependent MRI findings in symptomatic baseball players.

BACKGROUND: Elbow pain is common among youth baseball players and elbow MRI is increasingly utilized to complement the clinical assessment. OBJECTIVE: To characterize, according to skeletal maturity, findings on elbow MRI from symptomatic youth baseball players. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant retrospective study included pediatric (<18 years of age) baseball players with elbow pain who underwent MRI examinations between 2010 and 2021. Two radiologists, blinded to the outcome, independently reviewed examinations to categorize skeletal maturity and to identify osseous and soft tissue findings with consensus used to resolve discrepancies. Findings were compared between skeletally immature and mature patients and logistic regression models identified predictors of surgery. RESULTS: This study included 130 children (115 boys, 15 girls): 85 skeletally immature and 45 mature (12.8±2.3 and 16.2±1.0 years, respectively, p<0.01). Kappa coefficient for interobserver agreement on MRI findings ranged from 0.64 to 0.96. Skeletally immature children, when compared to mature children, were more likely to have elbow effusion (27%, 23/85 vs 9%, 4/45; p=0.03), medial epicondyle marrow edema (53%, 45/85 vs 16%, 7/45; p<0.01), avulsion fracture (19%, 16/85 vs 2%, 1/45; p=0.02), and juvenile osteochondritis dissecans (OCD, 22%, 19/85 vs 7%, 3/45; p=0.04), whereas skeletally mature children were more likely to have sublime tubercle marrow edema (49%, 22/45 vs 11%, 9/85; p<0.01) and triceps tendinosis (40%, 18/45 vs 20%, 17/85; p=0.03). Intra-articular body (OR=4.2, 95% CI 1.5-47.8, p=0.02) and osteochondritis dissecans (OR=3.7, 95% CI 1.1-11.9, p=0.03) were independent predictors for surgery. CONCLUSION: Differential patterns of elbow MRI findings were observed among symptomatic pediatric baseball players based on regional skeletal maturity. Intra-articular body and osteochondritis dissecans were independent predictors of surgery.

Early Outcomes Following Plantar Condylectomy and Imbrication of Plantar Plate to Metatarsal Neck for Metatarsalgia and Grade 0 Lesser Toe Metatarsophalangeal Joint Instability.

Background: Metatarsalgia and plantar plate tears are characterized by forefoot pain and toe deformity in severe cases. Conservative management may slow progression of symptoms; however, definitive treatment often requires operative intervention. The purpose of this observational study was to evaluate the combination of plantar condylectomy and surgical imbrication of the plantar plate to the metatarsal neck to repair grade 0 plantar plate injuries. Methods: We retrospectively identified 22 patients with metatarsalgia and low-grade plantar plate lesions (grade 0), operated between 2018 and 2021, who underwent operative repair involving plantar metatarsal condylectomy and proximal surgical imbrication of the plantar plate to the metatarsal neck. Fourteen patients underwent concomitant hallux valgus correction. Data collection was performed preoperatively and postoperatively and included Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) scores. Paired Wilcoxon signed-rank tests compared PROMIS PF and PI scores at patients' preoperative, 6-9-week, 3-4-month, 5-6-month, and ≥9-month follow-up evaluations (P < .05). Results: Compared to their preoperative visit, patients demonstrated modest improvement in their PROMIS (pain and physical function) scores over the first ≥9 months postoperatively (median 13.0 months). Median preoperative and most recent PROMIS physical function scores were 40.5 (95% CI: 36-49) and 44.5 (95% CI: 40-52), respectively. Median PROMIS pain interference scores changed from 62.5 (95% CI: 56-67) to 56.0 (95% CI: 51-62). Improvement in pain and function was sustained in patients available for postoperative follow-up. Conclusion: In this small, early follow-up series, we found that plantar condylectomy and surgical imbrication of the plantar plate to the metatarsal neck was modestly helpful to treat metatarsalgia and grade 0 plantar plate injuries. Level of Evidence: Level IV, retrospective case series.

Maturation-dependent patterns of knee injuries among symptomatic pediatric soccer players on MRI.

OBJECTIVE: To systematically investigate the prevalence of knee MRI findings among symptomatic pediatric soccer players with respect to skeletal maturity and to identify predictors of surgery. METHODS: This IRB-approved, HIPAA-compliant retrospective study included soccer players (< 18 years of age) who underwent MRI examinations in the past 5 years (2018-2023). Two radiologists retrospectively and independently reviewed all examinations to categorize skeletal maturity and to identify osseous and soft tissue findings. Findings were compared between maturation groups, and logistic regression models were used to identify predictors of surgery. RESULTS: Ninety-seven players (45 boys, 52 girls) included 39 skeletally immature, 21 maturing, and 37 mature knees. Kappa coefficient for interobserver reliability ranged between 0.65 and 1.00. Osgood-Schlatter disease (OSD) was more common among immature than maturing and mature knees (25% vs 14% and 5%, p = 0.04); anterior cruciate ligament (ACL) injury was more common among maturing and mature than immature knees (59% and 48%, vs 15%, p < 0.01); and meniscal tears were more common among mature than immature and maturing knees (medial, 41% vs 18% and 14%, p = 0.03; lateral, 43% vs 21% and 19%, p = 0.04). Players in the mature group were more likely to undergo surgery (p = 0.01). The presence of an effusion (OR = 19.5, 95% CI 2.8-240.9, p = 0.01), ACL injury (OR = 170.0, 95% CI 1.3-6996.9, p < 0.01), and lateral meniscal tears (OR = 10.8, 95% CI 1.8-106.1, p = 0.02) were independent predictors of surgery. CONCLUSION: Differential patterns of injury were found among symptomatic pediatric soccer players; the presence of an effusion, ACL injury, and lateral meniscal tears were independent predictors of surgery, likely contributing to the higher rates of surgery among skeletally mature players.

Correction: Referral for Cardiac Amyloidosis in Patients Who Underwent Transcatheter Aortic Valve Replacement: Results of the Quality Outcome Project.

[This corrects the article DOI: 10.7759/cureus.45024.].

Referral for Cardiac Amyloidosis in Patients Who Underwent Transcatheter Aortic Valve Replacement: Results of the Quality Outcome Project.

Background Transthyretin cardiac amyloidosis (ATTR) is an important comorbidity present in severe aortic stenosis (AS). The purpose of this study was to raise awareness of ATTR in patients who underwent transcatheter aortic valve replacement (TAVR) for severe AS among healthcare providers and patients. Methodology We reviewed 197 consecutive TAVR cases performed from 2019 to 2020. Adapting predefined high-risk features for ATTR based on prior literature, we contacted the patients to discuss our clinical suspicion of ATTR and offered a referral to a cardiac amyloid specialist. Results We identified 125 (69.4%) patients who had high-risk features of ATTR. Of the 105 patients contacted, 44 patients agreed to referral, 46 patients were not able to be contacted after several attempts, and 15 patients declined referral. Of the 44 patients who agreed to the referral, 20 patients completed the evaluation for cardiac amyloidosis, all of whom were negative for transthyretin and light-chain cardiac amyloidosis. Conclusions Our attempt to detect ATTR in prior TAVR patients was unsuccessful two to three years post-TAVR. We believe that early detection of cardiac amyloidosis close to the timing of TAVR is important and the most effective means.

Compartment Syndrome After Tibial Intramedullary Nail Removal and Intramedullary Debridement: A Case Report.

CASE: A 45-year-old man who sustained an open tibial shaft fracture treated with intramedullary (IM) nailing 9 years earlier presented with persistent pain and concern for occult infection. He underwent tibial nail removal and debridement with reamer-irrigator-aspirator. Postoperative course was complicated by acute compartment syndrome. CONCLUSION: This is a unique case of postoperative compartment syndrome after IM debridement and tibial hardware removal. A high index of suspicion should be prioritized in patients who complain of severe or unexpected pain to mitigate delays in diagnosis and aid in early treatment.

Diagnostic thresholds and optimal collection protocol of salivary pepsin for gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver-operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time < 4% no GERD) and 50% with elevated acid exposure (GERD). Mean pepsin concentrations were significantly lower in the AM (22.6 ± 25.2 ng/mL) compared to post-prandial (44.5 ± 36.7 ng/mL) and PM (55.4 ± 47.0 ng/mL). Agreement between pepsin concentrations across 3 days was substantial for AM samples (kappa 0.61), with lower agreement for post-prandial and PM samples. A single AM pepsin concentration of 25 ng/mL was 67% accurate for GERD with 56% sensitivity and 78% specificity. This validation study highlights fair accuracy and performance characteristics of a single fasting AM salivary pepsin concentration for the diagnosis of GERD.

Rates and reasons for reoperation within 30 and 90 days following cervical spine surgery: a retrospective cohort analysis of the Michigan Spine Surgery Improvement Collaborative (MSSIC) registry.

BACKGROUND CONTEXT: Reoperation following cervical spinal surgery negatively impacts patient outcomes and increases health care system burden. To date, most studies have evaluated reoperations within 30 days after spine surgery and have been limited in scope and focus. Evaluation within the 90-day period, however, allows a more comprehensive assessment of factors associated with reoperation. PURPOSE: The purpose of this study is to assess the rates and reasons for reoperations after cervical spine surgery within 30 and 90 days. DESIGN: We performed a retrospective analysis of a state-wide prospective, multi-center, spine-specific database of patients surgically treated for degenerative disease. PATIENT SAMPLE: Patients 18 years of age or older who underwent cervical spine surgery for degenerative pathologies from February 2014 to May 2019. Operative criteria included all degenerative cervical spine procedures, including those with cervical fusions with contiguous extension down to T3. OUTCOME MEASURES: We determined causes for reoperation and independent surgical and demographic risk factors impacting reoperation. METHODS: Patient-specific and surgery-specific data was extracted from the registry using ICD-10-DM codes. Reoperations data was obtained through abstraction of medical records through 90 days. Univariate analysis was done using chi-square tests for categorical variables, t-tests for normally distributed variables, and Wilcoxon rank-sum tests for variables with skewed distributions. Odds ratios for return to the operating room (OR) were evaluated in multivariate analysis. RESULTS: A total of 13,435 and 13,440 patients underwent cervical spine surgery and were included in the 30 and 90-day analysis, respectively. The overall reoperation rate was 1.24% and 3.30% within 30 and 90 days, respectively. Multivariate analysis showed within 30 days, procedures involving four or more levels, posterior only approach, and longer length of stay had increased odds of returning to the OR (p<.05), whereas private insurance had a decreased odds of return to OR (p<.05). Within 90 days, male sex, coronary artery disease (CAD), previous spine surgery, procedures with 4 or more levels, and longer length of stay had significantly increased odds of returning to the OR (p<.05). Non-white race, independent ambulatory status pre-operatively, and having private insurance had decreased odds of return to the OR (p<.05). The most common specified reasons for return to the OR within 30 days was hematoma (19%), infection (17%), and wound dehiscence (11%). Within 90 days, reoperation reasons were pain (10%), infection (9%), and hematoma (8%). CONCLUSION: Reoperation rates after elective cervical spine surgery are 1.24% and 3.30% within 30 and 90 days, respectively. Within 30 days, four or more levels, posterior approach, and longer length of stay were risk factors for reoperation. Within 90 days, male sex, CAD, four or more levels, and longer length of hospital stay were risk factors for reoperation. Non-white demographic and independent preoperative ambulatory status were associated with decreased reoperation rates.

Distribution of pediatric hand fractures: age- and bone maturation-dependent differences.

PURPOSE: To investigate the distribution and characteristics of fractures of bones of the hand on radiographs with respect to age and skeletal maturity of the fractured bone, and to identify predictors of surgery. METHODS: This cross-sectional, retrospective study included children (≤ 18 years) with hand fractures who underwent radiographic examinations (2019-2021). Fracture location, presence of displacement (≥ 2 mm), angulation (≥ 10°), articular extension, and if skeletally immature, then physeal involvement and Salter-Harris grade were recorded. Mann-Whitney U, Kruskal-Wallis, Fisher's exact, and chi-square tests as well as logistic regression analyses were used. RESULTS: Study group of 508 (350 boys, 158 girls; median age, 11.9 years) included 575 (63% phalangeal, 37% metacarpal, and 0.3% carpal) fractures. Younger children were more likely to sustain phalangeal and older children carpal and metacarpal fractures (median ages: 10.8 vs 12.3 and 13.8 years, p < 0.001); and fractures of the small finger accounted for 50% of metacarpal and 43% of phalangeal fractures. Fracture displacement (12% vs 22%, p = 0.02) and angulation (25% vs 49%, p < 0.001) were more common with mature than immature bones. A third of immature bones had physeal involvement and the most common pattern was Salter-Harris type II (89%). Surgical intervention was uncommon (11%) and independent predictors were displacement (OR = 3.99, 95% CI 1.95-8.19, p < 0.001) and articular extension (OR = 5.11, 95% CI 2.00-13.07, p < 0.001). CONCLUSION: While younger children were more likely to sustain phalangeal than metacarpal fractures and less likely to have displacement and angulation when compared to older children; only displacement and articular extension were significant independent predictors of surgery.

Pediatric hand fractures detection on radiographs: do localization cues improve diagnostic performance?

OBJECTIVE: To compare the diagnostic accuracy and interpretation time for detection of pediatric fractures on hand radiographs with and without localization cues. MATERIALS AND METHODS: Consecutive children, who underwent radiographic examinations after injury, over 2 years (2019-2021) and with > 2 weeks of follow-up to confirm the presence or absence of a fracture, were included. Four readers, blinded to history and diagnosis, retrospectively reviewed all images twice, without and with cue, at least 1 week apart and after randomization, to determine the presence or absence of a fracture, and if present, anatomic location and diagnostic confidence were recorded. Interpretation time for each study was also recorded and averaged across readers. Inter-reader agreement was calculated using Fleiss' kappa. Diagnostic accuracy and interpretation time were compared between examinations using sensitivity, specificity, and Mann-Whitney U correlation. RESULTS: Study group included 92 children (61 boys, 31 girls; 10.8 ± 3.4 years) with and 40 (31 boys, 9 girls; 10.9 ± 3.7 years) without fractures. Cue improved inter-reader agreement (κ = 0.47 to 0.62). While the specificity decreased (63 to 62%), sensitivity (75 to 78%), diagnostic accuracy (71 to 73%), and confidence improved (78 to 87%, p < 0.01), and interpretation time (median: 40 to 22 s, p < 0.001) reduced with examinations with localization cue. Specifically, examinations with fracture and cue had the shortest interpretation time (median: 16 s), whereas examinations without fracture and without cue had the longest interpretation time (median: 48 s). CONCLUSION: Localization cues increased inter-reader agreement and diagnostic confidence, reduced interpretation time in the detection of fractures on pediatric hand radiographs, while maintaining diagnostic accuracy.

Effect of Immunosuppressive Therapy and Biopsy Status in Monitoring Therapy Response in Suspected Cardiac Sarcoidosis.

BACKGROUND: Patients with suspected cardiac sarcoidosis frequently undergo fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging to assess disease activity at baseline and after treatment initiation. OBJECTIVES: This study investigated the effect of immunosuppressive therapy and biopsy status to achieve complete treatment response (CTR), partial treatment response (PTR), or no response (NR) on myocardial FDG-PET/CT. METHODS: This study analyzed 83 patients with suspected cardiac sarcoidosis (aged 53 ± 1.8 years, 71% were male, 69% were White, 61% had a history of biopsy-confirmed sarcoidosis) who were treatment naive, had evidence of myocardial FDG at baseline, and underwent repeat PET imaging after treatment initiation. CTR was graded visually, and PTR/NR were measured both visually and quantitatively using the total glycolytic activity. Patients were also evaluated for the occurrence of death, sustained ventricular arrhythmias, and heart failure admissions. RESULTS: Overall, 59 patients (71%) achieved CTR/PTR (30%/41%) at follow-up scan (P = 0.04). Total glycolytic activity and visual estimate of PTR/NR had excellent agreement (κ = 0.86 [95% CI: 0.72-0.99]; P < 0.0001). In patients receiving prednisone only, the highest rates of CTR/PTR were observed in patients initiated on moderate or high dose (P < 0.01). In a regression model, moderate prednisone start dose (P = 0.03) was more strongly associated with achieving CTR/PTR than was high prednisone start dose. However, the latter patients were tapered faster between start dose and follow-up scan (P < 0.01). After a median follow-up of 4.7 (IQR: 3.1-7.8) years, patients who were biopsy-proven (vs non-biopsy-proven; P = 0.029) and with preserved left ventricular function (P = 002) were less likely to experience major adverse cardiac events. Outcomes based on treatment response status (CTR vs PTR vs NR; P = 0.23) were not significantly different. CONCLUSIONS: Among patients with suspected sarcoidosis and evidence of myocardial inflammation, treatment response by serial FDG-PET was variable, but a favorable response was more common when using moderate-to-high intensity prednisone dose. Biopsy-proven individuals and those with preserved systolic function were less likely to experience adverse outcomes during follow-up.

Factors that Impact Day-to-Day Esophageal Acid Reflux Variability and Its Diagnostic Significance for Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common disease affecting a significant number of adults both globally and in the USA. GERD is clinically diagnosed based on patient-reported symptoms, and the gold standard for diagnosis is ambulatory reflux monitoring, a tool particularly utilized in the common scenario of non-response to therapy or atypical features. Over the past 20 years, there has been a shift toward extending the duration of reflux monitoring, initially from 24 to 48 h and more recently to 96 h, primarily based on a demonstrated increase in diagnostic yield. Further, multiple studies demonstrate clinically relevant variability in day-to-day acid exposure levels in nearly 30% of ambulatory reflux monitoring studies. For these reasons, an ongoing clinical dilemma relates to the optimal activities patients should engage in during prolonged reflux monitoring. Thus, the aims of this review are to detail what is known about variability in daily acid exposure, discuss factors that are known to influence this day-to-day variability (i.e., sleep patterns, dietary/eating habits, stress, exercise, and medications), and finally provide suggestions for patient education and general GERD management to reduce variation in esophageal acid exposure levels.

Salivary biomarkers and esophageal disorders.

Saliva is a complex physiologic fluid that contains an abundance of biological analytes, or biomarkers. Recent research has shown that these biomarkers may be able to convey the physiologic health of a person. Work has been done linking derangements in these salivary biomarkers to a wide variety of pathologic disorders ranging from oncologic diseases to atopic conditions. The specific area of interest for this review paper is esophageal disorders. Particularly because the diagnosis and management of esophageal disorders often includes invasive testing such as esophagogastroduodenoscopy, prolonged pH monitoring, and biopsy. The aim of this review will be to explore salivary biomarkers (pepsin, bile, epidermal growth factor, and micro-RNA) that are being studied as they relate specifically to esophageal disorders. Finally, it will explore the benefits of salivary testing and identify areas of possible future research.