MRI genicular nerve mapping: a novel approach to sagittal genicular nerve localization.

BACKGROUND AND OBJECTIVES: Chronic knee pain, including postarthroplasty knee pain, is a major cause of morbidity. Radiofrequency ablation of genicular nerve branches is a treatment option. The literature to date has demonstrated and recommended consistent rhizotomy targets in the coronal and axial position of the three primary genicular nerve branches (superomedial genicular nerve, superolateral genicular nerve, inferomedial genicular nerve). The debate on genicular nerve positions focuses on the anterior-posterior courses of the nerve branches. METHODS: The sagittal positions of the three primary genicular neurovascular bundles were measured in 28 consecutive knee MRI and described relative to the total anterior-posterior depth of the bony cortex. Standard radiofrequency capture radius at the classic rhizotomy targets sites was compared with identified nerve position to report proportion of observed nerves within the capture radius. RESULTS: The genicular neurovascular bundles were found further posterior than classic landmark targets. Proportion of visualized nerve branches captured by classic rhizotomy target radius varied by genicular nerve branch. CONCLUSIONS: This study supports updated guidance on genicular rhizotomy targets. Nerve localization studies using MRI data may be a promising avenue in future nerve localization research pertinent to rhizotomy.

Neonatal birthweight prediction using two- and three-dimensional estimated fetal weight among borderline small fetuses.

PURPOSE: This study aimed (1) to determine the degree of correlation between 2D and 3D estimated fetal weight (EFW) and neonatal birth weight (BW) among borderline small fetuses and (2) to compare the accuracy and precision of 2D and 3D EFW in BW prediction. METHODS: A retrospective cohort study evaluated fetuses who had an ultrasound performed between January 2017 and September 2021 at a tertiary maternal center. All singleton pregnancies with 3D EFW within 4 weeks of delivery were included. Fetuses with known structural or genetic abnormalities were excluded. Pearson's correlation coefficients were determined for both 2D and 3D EFW to BW then compared using Williams' test and Fisher r to z transformation, where applicable. Mean percent difference and standard deviation were used to assess the accuracy and precision, respectively, of 2D and 3D EFWs in BW prediction. RESULTS: Two hundred forty-eight pregnancies were included. Ultrasound studies were performed with a median interval of 2 weeks (IQR 1, 3) between ultrasound and delivery. Both 2D and 3D estimated fetal weights showed a significant correlation with birth weight (r = 0.74 and r = 0.73, respectively), indicating similar accuracy between the two techniques. CONCLUSION: Two-dimensional and three-dimensional EFWs performed similarly in the prediction of BW in borderline small fetuses.

Scanning the aged to minimize missed injury: An EAST multicenter study.

BACKGROUND: Despite the high incidence of blunt trauma in older adults, there is a lack of evidence-based guidance for computed tomography (CT) imaging in this population. We aimed to identify an algorithm to guide use of a Pan-Scan (Head/C-spine/Torso) or a Selective Scan (Head/C-spine ± Torso). We hypothesized that a patient's initial history and exam could be used to guide imaging. METHODS: We prospectively studied blunt trauma patients aged 65+ at 18 Level I/II trauma centers. Patients presenting >24 h after injury or who died upon arrival were excluded. We collected history and physical elements and final injury diagnoses. Injury diagnoses were categorized into CT body regions of Head/C-spine or Torso (chest, abdomen/pelvis, and T/L spine). Using machine learning and regression modeling as well as a priori clinical algorithms based, we tested various decision rules against our dataset. Our priority was to identify a simple rule which could be applied at the bedside, maximizing sensitivity (Sens) and negative predictive value (NPV) to minimize missed injuries. RESULTS: We enrolled 5,498 patients with 3,082 injuries. Nearly half (47.1%, n = 2,587) had an injury within the defined CT body regions. No rule to guide a Pan-Scan could be identified with suitable Sens/NPV for clinical use. A clinical algorithm to identify patients for Pan-Scan, using a combination of physical exam findings and specific high-risk criteria, was identified and had a Sens of 0.94 and NPV of 0.86 This rule would have identified injuries in all but 90 patients (1.6%) and would theoretically spare 11.9% (655) of blunt trauma patients a torso CT. CONCLUSIONS: Our findings advocate for Head/Cspine CT in all geriatric patients with the addition of torso CT in the setting of positive clinical findings and high-risk criteria. Prospective validation of this rule could lead to streamlined diagnostic care of this growing trauma population. LEVEL OF EVIDENCE: Level 2, Diagnostic Tests or Criteria.

Standardizing the Dosage and Timing of Dexamethasone for Postoperative Nausea and Vomiting Prophylaxis at a Safety-Net Hospital System.

BACKGROUND: A single dose of dexamethasone is routinely given during general anesthesia for postoperative nausea and vomiting (PONV) prophylaxis, although the exact dosage and timing of administration may vary between practitioners. The authors aimed to standardize the dosage and timing of this medication when given to adult patients undergoing general anesthesia for elective surgery. METHODS: Baseline data for 7,483 preintervention cases were analyzed. The researchers attempted to use a standard dose of 8 to 10 mg induction of anesthesia, which, based on a literature review, was effective for PONV prophylaxis, had a similar safety profile as a 4 to 5 mg dose (including in diabetic patients), and may confer additional benefits such as improved prophylaxis and quality of recovery. The interventions included standardizing the medication concentration vials, altering electronic health record quick-select button options, simplifying the intraoperative charting process, and educating the anesthesia providers. The research team then tracked compliance with the standard of care for 2,167 cases after the interventions. RESULTS: Overall compliance with the standard of care increased from 21.2% preintervention to 53.7% postintervention. The number of patients not receiving dexamethasone was reduced from 29.7% to 19.4%. Patients receiving a compliant dose at a noncompliant time increased from 16.3% to 23.8%. Postanesthesia care unit antiemetic administration also decreased after the interventions. CONCLUSION: This study showed improvements in compliance with the dosage of medication with the interventions. However, compliance with the timing of administration remains challenging.

The Association between Hormone Replacement Therapy and Gastroparesis in Post-Menopausal Women: A Worldwide Database Analysis.

Female sex hormones have been hypothesized to influence the higher prevalence of gastroparesis in females. This study investigated the effects of hormone replacement therapy (HRT) on gastroparesis and its related symptoms, medication use, and diagnostic testing in post-menopausal women. Utilizing the TriNetX platform, we conducted a population-based cohort study involving post-menopausal women aged 50 or older, with and without HRT. One-to-one propensity score matching was performed to adjust for age, race, ethnicity, diabetes, body mass index (BMI), and hemoglobin A1c. The exclusion criteria included functional dyspepsia, cyclic vomiting syndrome, and surgical procedures. After applying the exclusion criteria, we identified 78,192 post-menopausal women prescribed HRT and 1,604,822 not prescribed HRT. Post-propensity matching, each cohort comprised 67,874 patients. A total of 210 of the post-menopausal women prescribed HRT developed an ICD encounter diagnosis of gastroparesis at least 30 days after being prescribed HRT compared to post-menopausal women not prescribed HRT (OR = 1.23, 95% CI [1.01-1.51] p-value = 0.0395). These associations persisted in sensitivity analysis over 5 years (OR = 1.65, 95% CI [1.13-2.41] p-value = 0.0086). HRT was associated with increased GI symptoms, including early satiety (OR = 1.22, 95% CI [1.03-1.45] p-value = 0.0187), domperidone use (OR = 2.40, 95% CI [1.14-5.02] p-value = 0.0163), and undergoing gastric emptying studies (OR = 1.67, 95% CI [1.39-2.01] p-value < 0.0001). HRT is linked to an increased risk of developing an ICD encounter diagnosis of gastroparesis.

Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastro-oesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: a population-level retrospective matched cohort study.

BACKGROUND: Shorter half-life glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying (DGE) more than GLP-1 RAs with longer half-lives. DGE is a known risk factor for gastro-oesophageal reflux disease (GERD) and its complications. AIM: To determine whether short-acting or long-acting GLP-1 RAs are associated with an increased risk of new GERD or GERD-related complications DESIGN: We used the TriNetX global database to identify adult patients with type 2 diabetes mellitus and generated two cohorts totalling 1 543 351 patients on (1) GLP-1 RA or (2) other second-line diabetes medication. Using propensity-score matching, Kaplan-Meier Analysis and Cox-proportional hazards ratio (HR), we analysed outcomes and separately examined outcomes in patients starting short-acting (≤1 day) and long-acting (≥5 days) GLP-1 RAs. RESULTS: 177 666 patients were in each propensity-matched cohort. GLP-1 RA exposure was associated with an increased risk (HR 1.15; 95% CI 1.09 to 1.22) of erosive reflux disease (ERD). However, this was solely due to short-acting (HR 1.215; 95% CI 1.111 to 1.328), but not long-acting (HR 0.994; 95% CI 0.924 to 1.069) GLP-1 RA exposure. Short-acting GLP-1 RAs were also associated with increased risk of oesophageal stricture (HR 1.284; 95% CI 1.135 to 1.453), Barrett's without dysplasia (HR 1.372; 95% CI 1.217 to 1.546) and Barrett's with dysplasia (HR 1.505; 95% CI 1.164 to 1.946) whereas long-acting GLP-1 RAs were not. This association persisted in sensitivity analyses, and when individually examining the short-acting GLP-1 RAs liraglutide, lixisenatide and exenatide. CONCLUSION: Starting shorter-acting GLP-1 RAs is associated with increased risks of GERD and its complications.

Raloxifene increases the risk of gastroesophageal reflux disease, Barrett's esophagus, and esophageal stricture in postmenopausal women with osteoporosis.

BACKGROUND AND AIMS: Estrogen-based therapies may increase the risk of gastroesophageal reflux (GERD) and its complications. We aimed to determine the effect of raloxifene on the development of GERD, Barrett's esophagus, and esophageal stricture in postmenopausal women with osteoporosis. METHODS: This was a population-based, propensity-matched cohort study using the TriNetX platform. Patients 50 years and older with a diagnosis of "menopause" and "osteoporosis" were included in this study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for new GERD, esophageal stricture and Barrett's esophagus after raloxifene exposure. The control cohort consisted of patients who did not start any hormonal replacement therapy. We conducted a multivariable logistic regression analysis to evaluate the effect of confounding variables and also addressed common confounding medications with 1:1 propensity score-matching. Internal validity was confirmed by comparing to negative controls (lisinopril, atorvastatin) and positive controls (metformin, ibuprofen, aspirin). RESULTS: Five thousand four hundred and seventy two postmenopausal women with osteoporosis were on raloxifene of which 1908 (34.86%) developed GERD, compared to 296,067 postmenopausal who were not on raloxifene of which 90,643 (30.62%) developed GERD (OR 1.2; 95% CI 1.10-1.31, p < 0.0001). This persisted after adjusting for common medications known to affect GERD. Raloxifene was identified as a risk factor for GERD in a multivariate analysis, controlling for factors including age, obesity, smoking, and alcohol use (OR 1.51, 95% Wald CI 1.47-1.53). Raloxifene was associated with esophageal stricture (OR 1.60; 95% Wald CI 1.51-1.69) and Barrett's esophagus (OR 1.50; 95% Wald CI 1.37-1.63) in multivariate analysis. These associations persisted using sensitivity analyses. CONCLUSION: Raloxifene increases the risk of GERD, esophageal stricture and Barrett's esophagus in postmenopausal women with osteoporosis. Further studies are needed to confirm our findings.

Pre-appendectomy hyponatremia is associated with increased rates of complicated appendicitis.

Background: Acute appendicitis is one of the most common surgical emergencies worldwide. Preoperative assessment of the risk of complicated appendicitis may aid in treatment planning. We sought to investigate the association between pre-appendectomy hyponatremia and diagnosis of complicated appendicitis. Methods: The TriNetX platform, a federated health research network that aggregates de-identified electronic health record data of over 90 million patients across the United States, was queried for patients who underwent appendectomy starting January 2019 and who had at least one sodium value from the preoperative period. The study population was stratified into three age groups: pediatric (age < 18), adult (age 18-64), and older adult (age ≥ 65). These groups were subdivided into patients with preoperative hyponatremia (<135 mmol/L) and normonatremia (135-145 mmol/L). Results: Among the 61,245 patients who met inclusion criteria, 17,546 were included for analysis following propensity score matching. The odds of complicated appendicitis were highest in pediatric patients (age < 18) with pre-appendectomy hyponatremia (odds ratio [OR] = 2.91, 95 % CI [2.53, 3.35]). Patients age 18-64 and aged ≥ 65 with preoperative hyponatremia also demonstrated increased odds of a complicated appendicitis diagnosis, but to a lesser extent (OR = 2.11, 95 % CI [1.92, 2.32] (OR = 1.49, 95 % CI [1.25, 1.77], respectively). Conclusions: In a large analysis of matched patients with acute appendicitis, we found an association between immediate preoperative hyponatremia and complicated appendicitis. Future studies are indicated to further evaluate the role of hyponatremia as a potential diagnostic marker for complicated appendicitis in all age groups. Key message: This study suggests a role of hyponatremia as one of multiple variables to incorporate into future clinical decision tools for complicated acute appendicitis.

Physical activity has a stronger correlation with arterial stiffness than strength, balance, or BMI in an older population.

Background: Arterial stiffness is associated with an array of debilitating health conditions. While exercise typically has beneficial effects on both arterial stiffness and overall health, more research is needed to understand the associations of different types of fitness indices with arterial stiffness. Aim: To investigate the relationship between balance, strength, cardiovascular fitness and physical activity with arterial stiffness (as measured by pulse wave velocity (PWV)) in older adults. Method: Eighty retirement-village residents (24 males, 56 females, age: 78.2 ± 6.4 years, weight: 69.4 ± 12.5 kg, height: 162.9 ± 8.5 cm) completed the Yale Physical Activity Survey, PWV measurement, 30-s sit-to-stand leg strength test, hand grip strength assessment, 4-stage balance test, and a 6-min walk fitness test. The number of exiting risk factors (smoking, previous heart incidents, previous stroke(s), having hypertension, or taking anti-hypertension medication) were tallied. Pearson's correlations were used to assess the relationship between PWV and health and fitness parameters. Results were interpreted using qualitative inference. Results: The number of risk factors (r = 0.57, p < 0.001), age (r = 0.51, p < 0.001) and systolic blood pressure (r = 0.50, p = 0.001) had strong, harmful associations with PWV. Total physical activity minutes/week (r = -0.31 p = 0.01), total energy expenditure Kcal/week (r = -0.30, p = 0.01), and the 6-min walk test (r = -0.29, p = 0.01) had a moderate, beneficial association with PWV, while sit-to-stand (r = -0.27, p = 0.02) and balance (r = -0.27, p = 0.01) had a weak, beneficial association with PWV. Hand grip strength (r = 0.02, p = 0.94) and body mass index (r = -0.04, p = 0.75) had no significant associations with PWV. Discussion: All measured fitness indices had beneficial associations with PWV. However, having more risk factors, increased age, and higher systolic blood pressure had significant (harmful) associations with PWV in our older population. Conclusion: Controlling cardiovascular risk factors, especially high systolic blood pressure, is likely to have the largest beneficial effect on PWV. Improving general physical activity, including walking capacity, may prove beneficial in improving PWV in an older population.

Fibromuscular Dysplasia and Abdominal Aortic Aneurysms Are Dimorphic Sex-Specific Diseases With Shared Complex Genetic Architecture.

BACKGROUND: The risk of arterial diseases may be elevated among family members of individuals having multifocal fibromuscular dysplasia (FMD). We sought to investigate the risk of arterial diseases in families of individuals with FMD. METHODS: Family histories for 73 probands with FMD were obtained, which included an analysis of 463 total first-degree relatives focusing on FMD and related arterial disorders. A polygenic risk score for FMD (PRSFMD) was constructed from prior genome-wide association findings of 584 FMD cases and 7139 controls and evaluated for association with an abdominal aortic aneurysm (AAA) in a cohort of 9693 AAA cases and 294 049 controls. A previously published PRSAAA was also assessed among the FMD cases and controls. RESULTS: Of all first degree relatives of probands, 9.3% were diagnosed with FMD, aneurysms, and dissections. Aneurysmal disease occurred in 60.5% of affected relatives and 5.6% of all relatives. Among 227 female first-degree relatives of probands, 4.8% (11) had FMD, representing a relative risk (RR)FMD of 1.5 ([95% CI, 0.75-2.8]; P=0.19) compared with the estimated population prevalence of 3.3%, though not of statistical significance. Of all fathers of FMD probands, 11% had AAAs resulting in a RRAAA of 2.3 ([95% CI, 1.12-4.6]; P=0.014) compared with population estimates. The PRSFMD was found to be associated with an AAA (odds ratio, 1.03 [95% CI, 1.01-1.05]; P=2.6×10-3), and the PRSAAA was found to be associated with FMD (odds ratio, 1.53 [95% CI, 1.2-1.9]; P=9.0×10-5) as well. CONCLUSIONS: FMD and AAAs seem to be sex-dimorphic manifestations of a heritable arterial disease with a partially shared complex genetic architecture. Excess risk of having an AAA according to a family history of FMD may justify screening in family members of individuals having FMD.

Spontaneous coronary artery dissection is infrequent in individuals with heritable thoracic aortic disease despite partially shared genetic susceptibility.

Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N = 9), including COL3A1 (N = 3), FBN1 (N = 2), TGFBR2 (N = 2), TGFBR1 (N = 1), and PRKG1 (N = 1). Individuals with SCAD had an increased frequency of iliac artery dissection (25.0% vs. 5.1%, p = 0.047). The prevalence of SCAD among individuals with TAD is low. The identification of pathogenic variants in genes previously described in individuals with SCAD, particularly those underlying vascular Ehlers-Danlos, Marfan syndrome, and Loeys-Dietz syndrome, is consistent with prior reports from clinical SCAD series. Further research is needed to identify specific genetic influences on SCAD risk.

A Novel Recurrent COL5A1 Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia.

OBJECTIVE: While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in COL5A1 underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Results: We studied 4 independent probands with the COL5A1 pathogenic variant c.1540G>A, p.(Gly514Ser) who presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. Arterial medial fibroplasia and smooth muscle cell disorganization were confirmed histologically. The COL5A1 c.1540G>A variant is predicted to be pathogenic in silico and absent in gnomAD. The c.1540G>A variant is on a shared 160.1 kb haplotype with 0.4% frequency in Europeans. Furthermore, exome sequencing data from a cohort of 264 individuals with mFMD were examined for COL5A1 variants. In this mFMD cohort, COL5A1 c.1540G>A and 6 additional relatively rare COL5A1 variants predicted to be deleterious in silico were identified and were associated with arterial dissections (P=0.005). CONCLUSIONS: COL5A1 c.1540G>A is the first recurring variant recognized to be associated with arterial dissections and mFMD. This variant presents with a phenotype reminiscent of vascular Ehlers-Danlos syndrome. A shared haplotype among probands supports the existence of a common founder. Relatively rare COL5A1 genetic variants predicted to be deleterious by in silico analysis were identified in ≈2.7% of mFMD cases, and as they were enriched in patients with arterial dissections, may act as disease modifiers. Molecular testing for COL5A1 should be considered in patients with a phenotype overlapping with vascular Ehlers-Danlos syndrome and mFMD.