Validated Clinical Score to Predict Gastroesophageal Reflux in Patients With Chronic Laryngeal Symptoms: COuGH RefluX.

BACKGROUND & AIMS: Discerning whether laryngeal symptoms result from gastroesophageal reflux is clinically challenging and a reliable tool to stratify patients is needed. We aimed to develop and validate a model to predict the likelihood of gastroesophageal reflux disease (GERD) among patients with chronic laryngeal symptoms. METHODS: This multicenter international study collected data from adults with chronic laryngeal symptoms who underwent objective testing (upper gastrointestinal endoscopy and/or ambulatory reflux monitoring) between March 2018 and May 2023. The training phase identified a model with optimal receiver operating characteristic curves, and ß coefficients informed a weighted model. The validation phase assessed performance characteristics of the weighted model. RESULTS: A total of 856 adults, 304 in the training cohort and 552 in the validation cohort, were included. In the training phase, the optimal predictive model (area under the curve, 0.68; 95% CI, 0.62-0.74), was the Cough, Overweight/obesity, Globus, Hiatal Hernia, Regurgitation, and male seX (COuGH RefluX) score, with a lower threshold of 2.5 and an upper threshold of 5.0 to predict proven GERD. In the validation phase, the COuGH RefluX score had an area under the curve of 0.67 (95% CI, 0.62-0.71), with 79% sensitivity and 81% specificity for proven GERD. CONCLUSIONS: The externally validated COuGH RefluX score is a clinically practical model to predict the likelihood of proven GERD. The score classifies most patients with chronic laryngeal symptoms as low/high likelihood of proven GERD, with only 38% remaining as indeterminate. Thus, the COuGH RefluX score can guide diagnostic strategies and reduce inappropriate proton pump inhibitor use or testing for patients referred for evaluation of chronic laryngeal symptoms.

Laryngeal Recalibration Therapy Improves Laryngopharyngeal Symptoms in Patients With Suspected Laryngopharyngeal Reflux Disease.

INTRODUCTION: Laryngopharyngeal symptoms such as cough, throat clearing, voice change, paradoxic vocal fold movement, or laryngospasm are hyper-responsive behaviors resulting from local irritation (e.g., refluxate) and heightened sympathetic tone. Laryngeal recalibration therapy (LRT) guided by a speech-language pathologist (SLP) provides mechanical desensitization and cognitive recalibration to suppress hyper-responsive laryngeal patterns. The aim of this study was to assess symptom response to LRT among patients with chronic laryngopharyngeal symptoms undergoing evaluation of gastroesophageal reflux disease (GERD). METHODS: Adults with chronic laryngopharyngeal symptoms referred for evaluation of GERD to a single center were prospectively followed. Inclusion criteria included ≥2 SLP-directed LRT sessions. Data from endoscopy, ambulatory reflux monitoring, and patient-reported outcomes were collected when available. The primary outcome was symptom response. RESULTS: Sixty-five participants completed LRT: mean age 55.4 years (SD 17.2), 46 (71%) female, mean body mass index 25.6 kg/m 2 (6.8), and mean of 3.7 (1.9) LRT sessions. Overall, 55 participants (85%) met criteria for symptom response. Specifically, symptom response was similar between those with isolated laryngopharyngeal symptoms (13/15, 87%) and concomitant laryngopharyngeal/esophageal symptoms (42/50, 84%). Among participants who underwent reflux monitoring, symptom response was similar between those with proven, inconclusive for, and no GERD (18/21 [86%], 8/9 [89%], 10/13 [77%]). DISCUSSION: Eighty-five percent of patients with chronic laryngopharyngeal symptoms referred for GERD evaluation who underwent LRT-experienced laryngeal symptom response. Rates of symptom response were maintained across patients with or without proven GERD and patients with or without concomitant esophageal reflux symptoms. SLP-directed LRT is an effective approach to incorporate into multidisciplinary management of chronic laryngopharyngeal symptoms/laryngopharyngeal reflux disease.

Diagnostic Yield of Ambulatory Reflux Monitoring Systems for Evaluation of Chronic Laryngeal Symptoms.

INTRODUCTION: Among patients with chronic laryngeal symptoms, ambulatory reflux monitoring off acid suppression is recommended to evaluate for laryngopharyngeal reflux (LPR). However, reflux monitoring systems are diverse in configuration and monitoring capabilities, which present a challenge in creating a diagnostic reference standard in these patients. This study aimed to compare diagnostic yield and performance between reflux monitoring systems in patients with chronic laryngeal symptoms. METHODS: This multicenter, international study of adult patients referred for evaluation of LPR over a 5-year period (March 2018-May 2023) assessed and compared diagnostic yield of pathologic gastroesophageal reflux (GER+) on ambulatory reflux monitoring off acid suppression. RESULTS: Of 813 patients, 296 (36%) underwent prolonged wireless pH, 532 (65%) underwent 24-hour pH-impedance monitoring, and 15 (2%) underwent both tests. Overall diagnostic yield for GER+ was 36% and greater for prolonged wireless pH compared with that for 24-hour pH-impedance monitoring (50% vs 27%; P < 0.01). Among 15 patients who underwent both prolonged wireless pH and 24-h pH-impedance monitoring, concordance between systems for GER+ was 40%. The most common source of discordance was strong evidence of GER+ across multiple days on prolonged wireless pH compared with no evidence of GER+ on pH-impedance. DISCUSSION: In this multicenter international study of patients with chronic laryngeal symptoms referred for LPR evaluation, diagnostic yield of ambulatory reflux monitoring off acid suppression was 36% and rose to 50% when using wireless pH monitoring. In patients referred for chronic laryngeal symptoms, 24-hour pH-impedance monitoring may risk a low negative predictive value in patients with unproven GER+ disease.

The Adherence to an Intraoperative Blood Product Transfusion Algorithm Is Associated With Reduced Blood Product Transfusions in Cardiac Surgical Patients Undergoing Coronary Artery Bypass Grafts and Aortic and/or Valve Replacement Surgery: A Single-Center, Observational Study.

OBJECTIVE: To demonstrate the value of a viscoelastic-based intraoperative transfusion algorithm to reduce non-RBC product administration in adult cardiac surgical patients. DESIGN: A prospective observational study. SETTING: At a quaternary academic teaching hospital. PARTICIPANTS: Cardiac surgical patients. INTERVENTIONS: Viscoelastic-based intraoperative transfusion algorithm. MEASUREMENTS AND MAIN RESULTS: The study authors compared intraoperative blood product transfusion rates in 184 cardiac surgical patients to 236 historic controls after implementing a viscoelastic-based algorithm. The authors found a non-significant reduction in transfusion of 23.8% for fresh frozen plasma (FFP) units (0.84 ± 1.4 v 0.64 ± 1.38; p = ns), 33.4% for platelet units (0.90 ± 1.39 v 0.60 ± 131; p = ns), and 15.8% for cryoprecipitate units (0.19 ± 0.54 v 0.16 ± 0.50; p = ns). They found a 43.9% reduction in red blood cell (RBC) units transfused (1.98 ± 2.24 v 0.55 ± 1.36; p = 0.008). There were no statistically significant differences in time to extubation (8.0 hours (4.0-21.0) v 8.0 (4.0-22.3), reoperation for bleeding (15 [12.3%] v 10 [10.6%]), intensive care unit length of stay (ICU LOS) (51.0 hours [28.0-100.5] v 53.5 [33.3-99.0]) or hospital LOS (9.0 days [6.0-15.0] v 10.0 [7.0-17.0]). Deviation from algorithm adherence was 32.7% (48/147). Packed RBC, FFP, platelets, cryoprecipitate, and cell saver were significantly reduced in the Algorithm Compliant Cohort compared with historic controls, whereas times to extubation, ICU LOS, and hospital LOS did not reach significance. CONCLUSIONS: After the implementation of a viscoelastic-based algorithm, patients received fewer packed RBC, FFP, platelets, cryoprecipitate, and cell saver. Algorithm-compliant patients received fewer transfusions; however, reductions in times to extubation, ICU LOS, and hospital LOS were not statistically significant compared with historic controls.

Low-risk pneumatosis intestinalis in the pediatric surgical population.

BACKGROUND: Pneumatosis intestinalis (PI, presence of air in bowel wall) develops in a variety of settings and due to a variety of insults which is then characterized by varying severity and clinical course. Anecdotally, many of these cases are benign with few clinical sequelae; however, we lack evidence-based guidelines to help guide management of such lower-risk cases. We aimed to describe the clinical entity of low-risk PI, characterize the population of children who develop this form of PI, determine if management approach or clinical outcomes differed depending on the managing physician's field of practice, and finally determine if a shortened course of NPO and antibiotics was safe in the population of children with low-risk PI. METHODS: We performed a retrospective review of all children over age 1 year treated at Children's Hospital Colorado (CHCO), between 2009 and 2019 with a diagnosis of PI who did not also have a diagnosis of cancer or history of bone marrow transplant (BMT). Data including demographic variables, clinical course, and outcomes were obtained from the electronic medical record. Low-risk criteria included no need for ICU admission, vasopressor use, or urgent surgical intervention. RESULTS: Ninety-one children were treated for their first episode of PI during the study period, 72 of whom met our low-risk criteria. Among the low-risk group, rates of complications including hemodynamic decompensation during treatment, PI recurrence, Clostridium difficile colitis, and death did not differ between those who received 3 days or less of antibiotics and those who received more than 3 days of antibiotics. Outcomes also did not differ between children cared for by surgeons or pediatricians. CONCLUSIONS: Here, we define low-risk PI as that which occurs in children over age 1 who do not have a prior diagnosis of cancer or prior BMT and who do not require ICU admission, vasopressor administration, or urgent surgical intervention. It is likely safe to treat these children with only 3 days of antibiotic therapy and NPO. LEVEL OF EVIDENCE: Level III.

Lidocaine Intraoperative Infusion Pharmacokinetics during Partial Hepatectomy for Living Liver Donation.

BACKGROUND: Postoperative pain associated with open partial hepatectomy can be intense and persistent. The multimodal approach used to lessen this problem includes an intraoperative intravenous infusion of lidocaine hydrochloride. Decreased hepatic metabolism after resection raises concerns about safe lidocaine dosing in this patient population. The hypothesis was that the elimination clearance of lidocaine and its metabolites, monoethylglycinexylidide and glycinexylidide, is reduced after a partial hepatectomy, as reflected by observed plasma concentrations that are higher and have a longer half-life than expected based on pharmacokinetic modeling (estimated for normal liver function). Secondarily, this study postulated that plasma concentrations of lidocaine, monoethylglycinexylidide, and glycinexylidide do not reach toxic concentrations with institutional protocol up to 24 h after surgery. METHODS: Blood samples were collected from 15 patients undergoing a partial hepatectomy for living liver donation, at the following specific time points: before and immediately after induction of anesthesia, during hepatectomy, 30 min after hepatectomy completion, at case end, and 24 h after the end of surgery. Plasma concentrations of lidocaine and metabolites were measured by liquid chromatography-mass spectrometry. The population lidocaine pharmacokinetics were estimated, and total body weight and the fraction of remaining liver mass as potential model covariates were evaluated. The detection of any lidocaine, monoethylglycinexylidide, or glycinexylidide toxic plasma concentrations at any time point during and after hepatectomy were also evaluated. RESULTS: The typical value for lidocaine elimination clearance was 0.55 ± 0.12 l/min (± standard error of the estimate) which, on average, was reduced to about one third of the baseline clearance, 0.17 ± 0.02 l/min, once the donor graft was surgically isolated, and remained so for 24 h according to the current data and model. The fraction of remaining liver was a significant covariate for the posthepatectomy lidocaine clearance' such that if 50% of the liver is removed the clearance is reduced by approximately 60%. Plasma concentrations of lidocaine and its metabolites remained below their theoretical combined toxic threshold concentrations throughout the surgical and postoperative course in all patients, with one exception obtained near induction of anesthesia. Plasma lidocaine concentrations decreased at case end and postoperatively, while metabolite concentrations continued to rise at the end of surgery with reduction postoperatively. Pharmacokinetic modeling revealed that the only significant covariate in the model was the fraction of liver remaining after isolation of the donor graft. CONCLUSIONS: Intravenous lidocaine infusions are an acceptable option for multimodal pain management in patients undergoing a hepatectomy for living donation if the lidocaine infusion is stopped when the liver resection is complete. Clearance of lidocaine is decreased proportionally to the remaining liver mass, which should guide lidocaine infusion administration or dosing adjustments for patients undergoing liver resection surgery.

Effects of cohort, genotype, variant, and maternal ß-blocker treatment on foetal heart rate predictors of inherited long QT syndrome.

AIMS: In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal ß-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS. METHODS AND RESULTS: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal ß-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or ß-adrenergic response) had lower FHR. Maternal ß-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity. CONCLUSION: Genotype, LQT1 variant, and maternal ß-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.

Prelude to PATHWEIGH: pragmatic weight management in primary care.

OBJECTIVE: Treatment of obesity-related diseases, rather than obesity itself, remains the mainstay of medical care. The current study examined a novel approach that prioritizes weight management in primary care to shift this paradigm. METHODS: PATHWEIGH is a weight management approach consisting of staff team training, workflow system management, and data capture from tools built into the electronic medical record (EPIC). PATHWEIGH was compared to standard of care (SOC) using two family medicine clinics in the same US healthcare system. Descriptive statistics compared patient-, provider-, and clinic-level factors between the groups among those with at least one weight-prioritized visit (WPV) and one follow-up weight over 14 months. RESULTS: Groups were similar in terms of total patient visits (7,353 vs. 7,984) and patients eligible for a WPV (i.e. >18 years + body mass index >25 kg/m2; 3,746 vs. 3,008, PATHWEIGH vs. SOC, respectively). However, more PATHWEIGH clinic patients (15.9% vs. 8.4%; P < 0.001) received at least one WPV. Although no difference was observed for average patient weight loss over 14 months (P = 0.991), the number of WPVs per patient was higher in PATHWEIGH (P < 0.001) and significantly associated with weight loss (P = 0.001), with an average decrease in weight of 0.55 kg per additional visit. CONCLUSIONS: Results from the current study demonstrate early success in changing the paradigm from treating weight-related comorbidities to treating weight in primary care.

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.

What is the role of neutropenia in pediatric cancer patients with pneumatosis intestinalis?

BACKGROUND: We aimed to identify prognostic indicators in pneumatosis intestinalis (PI) in a pediatric oncology population. We hypothesized that neutropenia would be an independent risk factor for adverse outcomes, including the need for abdominal operation to treat PI and for the development of recurrent PI. METHODS: We performed a retrospective review of all patients treated for PI between 2009 and 2019 with a diagnosis of cancer or history of bone marrow transplant (BMT). RESULTS: Sixty-eight children were treated for their first episode of PI; 15 (22%) were not neutropenic at presentation; eight underwent urgent abdominal operation (12%). Patients with neutropenia were more likely to receive TPN, had a longer course of NPO, and received a longer course of antibiotics. Neutropenia at presentation was associated with a decreased risk of PI recurrence (40% vs 13%, p = 0.03). Children who required an abdominal operation were more likely to require vasopressors at diagnosis (50% vs 10%, p = 0.013). CONCLUSIONS: Among pediatric cancer patients, need for vasopressors at the time of PI is a marker of severe PI, with increased likelihood of requiring operative intervention. The presence of neutropenia is associated with lower rates of PI recurrence. LEVEL OF EVIDENCE: Level III.

Lead and Pulse Generator Migration After Spinal Cord Stimulation Implantation: Insights From an Analysis of 7322 Patients.

OBJECTIVES: Lead migration (LM) after spinal cord stimulation (SCS) implantation surgery is the most common device-related complication. Our study of lead and implantable pulse generator (IPG) migration using a large administrative claims data base aims to understand rates, risk factors, and outcomes after SCS implantation. MATERIALS AND METHODS: This retrospective cohort study used the IBM® MarketScan® (Armonk, NY) Commercial and Medicare Supplemental Databases from 2016 to 2018. Adult patients who underwent SCS surgical procedures with at least 90 days of follow-up were identified using Current Procedural Terminology (CPT®) codes. Patients with LM and IPG migration after SCS surgery were identified using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10 CM) codes. Patients who underwent revision surgery after SCS implantation were identified using the CPT codes and ICD-10 CM codes. In addition, patient characteristics associated with LM or IPG migration, the temporal relationship of migration diagnosis, and revision surgery were evaluated in the cohort. Continuous outcomes were compared between groups using the two-sample Student t-test. The Fisher exact test was used to compare categorical outcomes between groups. RESULTS: A total of 7322 patients (64.4% percutaneous SCS) underwent SCS surgery during the study period. A total of 141 patients (1.9%) had LM or IPG migration. Of those, 116 patients (1.6%) had LM only; 18 patients (0.2%) had IPG migration; and seven patients (0.1%) had LM and IPG migration. The mean duration for migration diagnosis after initial SCS implantation was 168 (±163.1) days. The mean duration to revision surgery after the migration diagnosis was 12.3 (±35.2) days only. Most patients with migration (105, 74.5%) underwent revision surgery. Only younger age (p = 0.02) was associated with migration in this study. CONCLUSIONS: LM and pulse generator migration that required revision surgery occurred in a small proportion of patients who underwent SCS surgical procedures.

Ambulatory Reflux Monitoring Guides Proton Pump Inhibitor Discontinuation in Patients With Gastroesophageal Reflux Symptoms: A Clinical Trial.

BACKGROUND AND AIMS: Proton pump inhibitor (PPI) therapy fails to provide adequate symptom control in up to 50% of patients with gastroesophageal reflux symptoms. Although a proportion do not require ongoing PPI therapy, a diagnostic approach to identify candidates appropriate for PPI cessation is not available. This study aimed to examine the clinical utility of prolonged wireless reflux monitoring to predict the ability to discontinue PPIs. METHODS: This double-blinded clinical trial performed over 3 years at 2 centers enrolled adults with troublesome esophageal symptoms of heartburn, regurgitation, and/or chest pain and inadequate PPI response. Participants underwent prolonged wireless reflux monitoring (off PPIs for ≥7 days) and a 3-week PPI cessation intervention. Primary outcome was tolerance of PPI cessation (discontinued or resumed PPIs). Symptom burden was quantified using the Reflux Symptom Questionnaire electronic Diary (RESQ-eD). RESULTS: Of 128 enrolled, 100 participants met inclusion criteria (mean age, 48.6 years; 41 men). Thirty-four participants (34%) discontinued PPIs. The strongest predictor of PPI discontinuation was number of days with acid exposure time (AET) > 4.0% (odds ratio, 1.82; P < .001). Participants with 0 days of AET > 4.0% had a 10 times increased odds of discontinuing PPI than participants with 4 days of AET > 4.0%. Reduction in symptom burden was greater among the discontinued versus resumed PPI group (RESQ-eD, -43.7% vs -5.3%; P = .04). CONCLUSIONS: Among patients with typical reflux symptoms, inadequate PPI response, and absence of severe esophagitis, acid exposure on reflux monitoring predicted the ability to discontinue PPIs without symptom escalation. Upfront reflux monitoring off acid suppression can limit unnecessary PPI use and guide personalized management. (ClinicalTrials.gov, Number: NCT03202537).

Distinct Clinical Physiologic Phenotypes of Patients With Laryngeal Symptoms Referred for Reflux Evaluation.

BACKGROUND & AIMS: Heterogeneous presentations and disease mechanisms among patients with laryngeal symptoms account for misdiagnosis of laryngopharyngeal reflux (LPR), variations in testing, and suboptimal outcomes. We aimed to derive phenotypes of patients with laryngeal symptoms based on clinical and physiologic data and to compare characteristics across phenotypes. METHODS: A total of 302 adult patients with chronic laryngeal symptoms were prospectively enrolled at 3 centers between January 2018 to October 2020 (age 57.2 ± 15.2 years; 30% male; body mass index 27.2 ± 6.0 kg/m2). Discriminant analysis of principal components (DAPC) was applied to 12 clinical and 11 physiologic variables collected in stable condition to derive phenotypic groups. RESULTS: DAPC identified 5 groups, with significant differences across symptoms, hiatal hernia size, and number of reflux events (P < .01). Group A had the greatest hiatal hernia size (3.1 ± 1.0 cm; P < .001) and reflux events (37.5 ± 51; P < .001), with frequent cough, laryngeal symptoms, heartburn, and regurgitation. Group B had the highest body mass index (28.2 ± 4.6 kg/m2; P < .001) and salivary pepsin (150 ± 157 ng/mL; P = .03), with frequent cough, laryngeal symptoms, globus, heartburn, and regurgitation. Group C frequently reported laryngeal symptoms (93%; P < .001), and had fewest esophageal symptoms (9.6%; P < .001) and reflux events (10.7 ± 11.0; P < .001). Group D commonly reported cough (88%; P < .001) and heartburn. Group E (18%) was oldest (62.9 ± 14.3 years; P < .001) and distinguished by highest integrated relaxation pressure. CONCLUSIONS: DAPC identified distinct clinicophysiologic phenotypes of patients with laryngeal symptoms referred for reflux evaluation: group A, LPR and gastroesophageal reflux disease (GERD) with hiatal hernia; group B, mild LPR/GERD; group C, no LPR/No GERD; group D, reflex cough; and group E, mixed/possible obstructive esophagogastric junction. Phenotypic differences may inform targeted clinical trials design and improve outcomes.

Optimal Wireless Reflux Monitoring Metrics to Predict Discontinuation of Proton Pump Inhibitor Therapy.

INTRODUCTION: Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response. METHODS: This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to > 8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks. RESULTS: Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01). DISCUSSION: This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy.

Evaluation of Diaphragmatic Function after Interscalene Block with Liposomal Bupivacaine: A Randomized Controlled Trial.

BACKGROUND: Interscalene blocks provide analgesia for shoulder surgery but also cause phrenic nerve paralysis. Liposomal bupivacaine is approved for use in interscalene blocks with the potential to provide longer pain control. However, the impact of liposomal bupivacaine on the phrenic nerve has not been evaluated. It was hypothesized that patients who received an interscalene block with both bupivacaine and liposomal bupivacaine would have a decreased diaphragmatic excursion when compared to bupivacaine alone at 24 h. METHODS: This was a double-blinded study of adult patients who were randomized to receive an interscalene block with either 20 ml 0.5% bupivacaine (bupivacaine group) or 10 ml 0.5% bupivacaine plus 10 ml liposomal bupivacaine (liposomal bupivacaine group). Twenty-six patients were randomized with 22 included in the analysis. Diaphragmatic excursion (via ultrasound) and spirometry were assessed before the block, in the postanesthesia care unit, and at 24 h postblock. The primary outcome was diaphragm excursion with sigh. No adverse events were observed. RESULTS: At 24 h, the liposomal bupivacaine group median [25th, 75th], had a greater percent change in diaphragmatic excursion during sigh breath compared to the bupivacaine group, -24% [-30, -9] versus 9% [-8, 26], difference in location, 32 (95% CI, 12 to 52), P = 0.007. Five patients in the liposomal bupivacaine group had a greater than 25% reduction in diaphragmatic excursion at 24 h versus zero in the bupivacaine group. They also had a significantly greater percent reduction in forced expiratory volume in 1 s and forced vital capacity compared with the bupivacaine group at 24 h (median decrease of 22% vs. 2%, P = 0.006, and median decrease of 19% vs. 1%, P = 0.049, respectively). CONCLUSIONS: The addition of liposomal bupivacaine to bupivacaine in an interscalene block results in statistically significant reductions in diaphragm excursion and pulmonary function testing 24 h after block placement when compared to bupivacaine alone. This reduction, however, falls within the range of normal diaphragmatic function.

Reducing the burden of surveillance in pregnant women with no history of fetal atrioventricular block using the negative predictive value of anti-Ro/SSA antibody titers.

BACKGROUND: The risk of fetal atrioventricular block in anti-Ro/SSA antibody-exposed pregnancies with no previous affected offspring is approximately 2%. A high antibody titer is necessary but not sufficient for atrioventricular block, and specific antibody titers do not predict risk. However, there are no data on the negative predictive value of antibody titer to identify pregnancies at low risk of fetal atrioventricular block, and may not require surveillance. OBJECTIVE: This study aimed to define anti-Ro52 and anti-Ro60 antibody thresholds for the identification of fetuses unlikely to develop atrioventricular block using clinically validated and research laboratory tests. STUDY DESIGN: This study performed a multicenter review of pregnant subjects who tested positive in their local commercial laboratories for anti-Ro/SSA antibodies at the University of Colorado Children's Hospital (2014-2021) and Phoenix Children's Hospital (2014-2021) and enrolled in the Research Registry for Neonatal Lupus (RRNL) at New York University Langone Medical Center (2002-2021). The subjects were referred on the basis of rheumatologic symptoms or history of atrioventricular block in a previous pregnancy and were retrospectively grouped on the basis of pregnancy outcome. Group 1 indicated no fetal atrioventricular block in current or past pregnancies; group 2 indicated fetal atrioventricular block in the current pregnancy; and group 3 indicated normal current pregnancy but with fetal atrioventricular block in a previous pregnancy. Maternal sera were analyzed for anti-Ro52 and anti-Ro60 antibodies using a clinically validated multiplex bead assay (Associated Regional and University Pathologists Laboratories, Salt Lake City, UT) and a research enzyme-linked immunosorbent immunoassay (New York University). This study calculated the negative predictive value separately for anti-Ro52 and anti-Ro60 antibodies and for the 2 combined using a logistic regression model and a parallel testing strategy. RESULTS: This study recruited 270 subjects (141 in group 1, 66 in group 2, and 63 in group 3). Of note, 89 subjects in group 1 had data on hydroxychloroquine treatment: anti-Ro/SSA antibody titers were no different between those treated (n=46) and untreated (n=43). Mean anti-Ro52 and anti-Ro60 titers were the lowest in group 1 and not different between groups 2 and 3. No case of fetal atrioventricular block developed among subjects with anti-Ro52 and anti-Ro60 titers of <110 arbitrary units per milliliter using the multiplex bead assay of the Associated Regional and University Pathologists Laboratories (n=141). No case of fetal atrioventricular block developed among subjects with research laboratory anti-Ro52 titers of <650 and anti-Ro60 of <4060 enzyme-linked immunosorbent immunoassay units (n=94). Using these 100% negative predictive value thresholds, more than 50% of the anti-Ro/SSA antibody pregnancies that ultimately had no fetal atrioventricular block could be excluded from surveillance based on clinical and research titers, respectively. CONCLUSION: Study data suggested that there is a clinical immunoassay level of maternal anti-Ro/SSA antibodies below which the pregnancy is at low risk of fetal atrioventricular block. This study speculated that prospectively applying these data may avert the costly serial echocardiograms currently recommended for all anti-Ro/SSA-antibody positive pregnancies and guide future management.

Upper Esophageal Sphincter Compression Device as an Adjunct to Proton Pump Inhibition for Laryngopharyngeal Reflux.

BACKGROUND: The Reflux Band, an external upper esophageal sphincter (UES) compression device, reduces esophago-pharyngeal reflux events. This study aimed to assess device efficacy as an adjunct to proton pump inhibitor (PPI) therapy in patients with laryngopharyngeal reflux (LPR). METHODS: This two-phase prospective clinical trial enrolled adults with at least 8 weeks of laryngeal symptoms (sore throat, throat clearing, dysphonia) not using PPI therapy at two tertiary care centers over 26 months. Participants used double dose PPI for 4 weeks in Phase 1 and the external UES compression device nightly along with PPI for 4 weeks in Phase 2. Questionnaire scores and salivary pepsin concentration were measured throughout the study. The primary endpoint of symptom response was defined as reflux symptom index (RSI) score ≤ 13 and/or > 50% reduction in RSI. RESULTS: Thirty-one participants completed the study: 52% male, mean age 47.9 years (SD 14.0), and mean body mass index (BMI) 26.2 kg/m2 (5.1). Primary endpoint was met in 11 (35%) participants after Phase 1 (PPI alone) and 17 (55%) after Phase 2 (Device + PPI). Compared to baseline, mean RSI score (24.1 (10.9)) decreased at end of Phase 1 (PPI alone) (21.9 (9.7); p = 0.06) and significantly decreased at end of Phase 2 (Device + PPI) (15.5 (10.3); p < 0.01). Compared to non-responders, responders to Device + PPI had a significantly lower BMI (p = 0.02) and higher salivary pepsin concentration (p = 0.01). CONCLUSION: This clinical trial highlights the potential efficacy of the external UES compression device (Reflux Band) as an adjunct to PPI for patients with LPR (ClinicalTrials.Gov NCT03619811).

Anesthetic Management and Outcomes of Patients With Epidermolysis Bullosa: Experience at a Tertiary Referral Center.

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare epithelial disorders caused by abnormal or absent structural proteins at the epidermal-dermal junction. As a result, patients experience blisters and wounds from mild shearing forces. Some forms of EB are complicated by resultant scarring and contractures. The perioperative anesthetic management of patients with EB is complex and requires a systems-based approach to limit harm. We reviewed our experience with providing general anesthesia to patients at our tertiary EB referral center, including adverse events related to anesthetic care, outcomes in the immediate perioperative period, and details of anesthetic management. METHODS: We retrospectively reviewed the charts of all patients with EB anesthetized at the Children's Hospital Colorado between January 2011 and December 2016. A subset of pediatric anesthesiologists cared for all patients using a standardized clinical care pathway. Patient demographics, detailed anesthetic methods, immediate perioperative outcomes, and adverse events were characterized. RESULTS: Over a 6-year period, 37 patients underwent 202 general anesthetics. Most patients (75.7%) had dystrophic EB (DEB). Female patients comprised 48.6%. The majority (56.7%) traveled >50 miles to receive care, and many (35.1%) traveled >150 miles for their care. Common adaptations to care included avoidance of electrocardiogram leads (88.6%) and temperature probes (91.6%). Nasal fiberoptic intubation (n = 160) was performed, or natural airway/mask (n = 27) was maintained for most patients. Supraglottic devices were not used for airway management during any of the anesthetics. Anesthesia preparation time was longer (average 25.8 minutes [standard deviation {SD} = 12.7]) than our average institutional time (14 minutes). Succinylcholine was never used, and nondepolarizing muscle relaxants were used in only 1.5% of patient encounters. Blood was transfused in 16.3% of cases and iron infused in 24.8%. Average length of stay in the postanesthesia care unit was comparable to our institutional average (average 40.1 [SD = 28.6] vs 39 minutes). New skin or mucosal injury occurred in 8 encounters (4%), and desaturation occurred in 43 cases (21.3%). There were no major adverse events. CONCLUSIONS: By using a specialized team and a standardized clinical care pathway, our institution was able to minimize adverse events caused by the anesthetic and surgical care of patients with EB. We recommend natural airway or nasal fiberoptic airway management, meticulous avoidance of shear stress on the skin, and a multidisciplinary approach to care. Supportive therapy such as perioperative blood transfusions and iron infusions are feasible for the treatment of chronic anemia in this population.

Integrated Biomarkers for the Management of Indeterminate Pulmonary Nodules.

Rationale: Patients with indeterminate pulmonary nodules (IPNs) at risk of cancer undergo high rates of invasive, costly, and morbid procedures. Objectives: To train and externally validate a risk prediction model that combined clinical, blood, and imaging biomarkers to improve the noninvasive management of IPNs. Methods: In this prospectively collected, retrospective blinded evaluation study, probability of cancer was calculated for 456 patient nodules using the Mayo Clinic model, and patients were categorized into low-, intermediate-, and high-risk groups. A combined biomarker model (CBM) including clinical variables, serum high sensitivity CYFRA 21-1 level, and a radiomic signature was trained in cohort 1 (n = 170) and validated in cohorts 2-4 (total n = 286). All patients were pooled to recalibrate the model for clinical implementation. The clinical utility of the CBM compared with current clinical care was evaluated in 2 cohorts. Measurements and Main Results: The CBM provided improved diagnostic accuracy over the Mayo Clinic model with an improvement in area under the curve of 0.124 (95% bootstrap confidence interval, 0.091-0.156; P < 2 × 10-16). Applying 10% and 70% risk thresholds resulted in a bias-corrected clinical reclassification index for cases and control subjects of 0.15 and 0.12, respectively. A clinical utility analysis of patient medical records estimated that a CBM-guided strategy would have reduced invasive procedures from 62.9% to 50.6% in the intermediate-risk benign population and shortened the median time to diagnosis of cancer from 60 to 21 days in intermediate-risk cancers. Conclusions: Integration of clinical, blood, and image biomarkers improves noninvasive diagnosis of patients with IPNs, potentially reducing the rate of unnecessary invasive procedures while shortening the time to diagnosis.

The Use of a Viscoelastic-Based Transfusion Algorithm Significantly Reduces Non-red Blood Cell Transfusion in Patients Undergoing Left Ventricular Assist Device Placement or Heart Transplantation: A Single-Center Observational Study.

OBJECTIVES: Does point-of-care viscoelastic testing in patients undergoing left ventricular assist device implantation or orthotopic heart transplantation reduce non-red blood cell transfusion or improve postoperative outcomes? DESIGN: A retrospective observational study. SETTING: At a single-center tertiary university hospital. PARTICIPANTS: Patients undergoing left ventricular assist device placement or heart transplantation INTERVENTIONS: The authors implemented a TEG-based transfusion algorithm to reduce non-red cell transfusion rates compared with historical controls. MEASUREMENTS AND MAIN RESULTS: From May 15, 2019, through March 20, 2020, 68 patients underwent left ventricular assist device placement or heart transplantation. Algorithm adherence was 49.2%. After adjusting for relevant variables, platelet (odds ratio [OR] 0.58 [0.39-0.84]; p = 0.004) and cryoprecipitate (OR 0.37 [0.19-0.72]; p = 0.004) transfusion rates and time to extubation (OR -14.1 [-25.8 to -2.3]; p = 0.020) were significantly reduced compared with historical controls. After adjusting for relevant clinical variables, there was a statistically significant reduction in plasma (median [interquartile range] 0.16 [0.07-0.36], p < 0.001), platelets (0.06 [0.02-0.21], p < 0.001), and cryoprecipitate (0.06 [0.01-0.47], p = 0.007) transfusion rates and time to extubation (-16.95 [-27.20 to -6.71], p = 0.002) compared with historical controls. CONCLUSIONS: The authors report a statistically significant reduction in transfusion of platelets and cryoprecipitate and time to extubation after adjusting for relevant clinical variables compared with historical controls and a significant reduction in the transfusion of plasma, platelets, and cryoprecipitate and time to extubation in those patients for whom the transfusion algorithm was followed. Their results suggest the importance of implementing transfusion algorithms for patients undergoing heart transplantation and left ventricular assist device placement and of accounting for adherence.