Citations

The relationship of blood volume (BV) to systemic blood pressure (BP) is not well defined in resistant hypertension (RH). The goal of this study was to examine the extent to which systemic BP stratified by patient sex would impact BV phenotypes. A retrospective analysis of clinical and quantitative BV data was undertaken in a cohort of ambulatory patients with a history of controlled and uncontrolled RH. We analyzed 253 unique BVs with 54% of patients above goal BP of <150 mmHg. BV phenotypes were highly variable but no correlation of systolic BP to absolute BV or percentage deviation from normal volume was identified in either sex. Males demonstrated overall larger absolute BVs with higher prevalence of large plasma volume (PV) expansion; females were overall more hypovolemic by total BV but with a higher frequency of normal PV than males. Females trended towards more RBC mass deficit (true anemia) (49% vs. 38%. P = 0.084) while more males demonstrated RBC mass excess (erythrocythemia) (21% vs. 11%, P = 0.029). Importantly, a significant portion (52%) of patients with true anemia identified by BVA would go undetected by hemoglobin measurement alone. BV phenotypes are highly diverse in patients with RH. However, absolute BV or variability in BV phenotypes even when stratified by patient sex did not demonstrate an association with systemic BP. BV phenotyping provides a key to optimizing clinical management by identifying RBC mass profiles particularly distinguishing true anemia, dilutional anemia, and erythrocythemia and the contribution of PV expansion. Findings support the clinical utility of BV phenotyping in RH.

Key Points Kidney stones are common in patients with autosomal dominant polycystic kidney disease compared with matched controls with CKD. The increase in imaging seen in patients with autosomal dominant polycystic kidney disease correlates with the kidney stone burden in these patients. Background Patients with autosomal dominant polycystic kidney disease (ADPKD) may have more imaging studies than patients with other forms of CKD. We characterized the imaging burden of patients with ADPKD relative to a CKD population to determine which factors lead to increased imaging in patients with ADPKD. Methods We retrospectively reviewed patients seen at Yale Nephrology between January 2012 and January 2021. We collected demographic, clinical, and imaging data through automated query and manual chart review. Eight hundred seven patients with ADPKD were matched to 4035 CKD controls on the basis of criteria of sex, race, ethnicity, CKD stage, hypertension, and diabetes, but not age. The number of abdominal imaging studies were compared between ADPKD and CKD groups, and the effect of kidney stone diagnosis was further evaluated. Chi-square and t tests were used to evaluate demographic variables, and Kruskal Wallis and negative binomial regression models were used to evaluate differences between abdominal imaging studies. Results Patients with ADPKD had a greater number of total abdominal imaging studies ( P < 0.0001), ultrasounds ( P < 0.0001), and magnetic resonance imagings ( P = 0.02) compared with controls. In patients with preserved renal function (eGFR >60 ml/min per m 2 ), these differences persisted. Kidney stones were significantly more common among patients with ADPKD ( P < 0.0001). In multivariable assessment of imaging study counts using a negative binomial model controlling for kidney stones, ADPKD was no longer a significant predictor. In patients with ADPKD, pyelonephritis; cyst complications; lower eGFR; diabetes; coronary artery disease; kidney stones; lower body mass index; and being male, Black, and younger increased the likelihood of having more imaging studies. Conclusions The higher prevalence of abdominal imaging studies in patients with ADPKD correlated with the increased incidence of kidney stones observed in this population.

BACKGROUND: The COVID-19 pandemic has severely affected healthcare systems globally, resulting in significant delays and challenges in various medical treatments, particularly in cancer care. This study aims to investigate the repercussions of the pandemic on surgical interventions for colorectal cancer (CRC) in the US, using data from the National Cancer Database. STUDY DESIGN: We conducted a retrospective analysis of the National Cancer Database, encompassing adult patients who underwent surgical procedures for colon and rectal cancer in 2019 (pre-COVID) and 2020 (COVID). We examined various demographic and clinical variables, including patient characteristics, tumor staging, surgical approaches, and socioeconomic factors. RESULTS: The analysis included 105,517 patients, revealing a 17.3% reduction in surgical cases during the initial year of the pandemic. Patients who underwent surgery in 2020 displayed more advanced clinical and pathological tumor stages compared to those treated in 2019. After diagnosis, no delay was reported in the treatment. Patients operated during the pandemic, Black patients, uninsured, and Medicaid beneficiaries had worse stage colon and rectal cancer, and individuals with lower incomes bore the burden of advanced colon cancer. CONCLUSIONS: The impact of the COVID-19 pandemic on CRC surgery transcends a mere decline in case numbers, resulting in a higher prevalence of patients with advanced disease. This study underscores the exacerbated disparities in cancer care, particularly affecting vulnerable populations. The COVID-19 pandemic has left a significant and enduring imprint on CRC surgery, intensifying the challenges faced by patients and healthcare systems. Comprehensive studies are imperative to comprehend the long-term consequences of delayed screenings, diagnoses, and treatments as healthcare planning for the future must consider the unintended repercussions of pandemic-related disruptions.

AbstractPurposeAbnormal adherence at functional myofascial interfaces is hypothesized as an important phenomenon in myofascial pain syndrome. This study aimed to investigate the feasibility of MR elastography (MRE)–based slip interface imaging (SII) to visualize and assess myofascial mobility in healthy volunteers.MethodsSII was used to assess local shear strain at functional myofascial interfaces in the flexor digitorum profundus (FDP) and thighs. In the FDP, MRE was performed at 90 Hz vibration to each index, middle, ring, and little finger. Two thigh MRE scans were performed at 40 Hz with knees flexed and extended. The normalized octahedral shear strain (NOSS) maps were calculated to visualize myofascial slip interfaces. The entropy of the probability distribution of the gradient NOSS was computed for the two knee positions at the intermuscular interface between vastus lateralis and vastus intermedius, around rectus femoris, and between vastus intermedius and vastus medialis.ResultsNOSS map depicted distinct functional slip interfaces in the FDP for each finger. Compared to knee flexion, clearer slip interfaces and larger gradient NOSS entropy at the vastus lateralis–vastus intermedius interface were observed during knee extension, where the quadriceps are not passively stretched. This suggests the optimal position for using SII to visualize myofascial slip interface in skeletal muscles is when muscles are not subjected to any additional force.ConclusionThe study demonstrated that MRE‐based SII can visualize and assess myofascial interface mobility in extremities. The results provide a foundation for investigating the hypothesis that myofascial pain syndrome is characterized by changes in the mobility of myofascial interfaces.

Background and Purpose Spontaneous intracranial hypotension (SIH) is caused by spinal cerebrospinal fluid (CSF) leaks. This study assessed whether the certainty and/or multifocality of CSF leaks is associated with the severity of intracranial sequelae of SIH. Materials and Methods A retrospective review was completed of patients with suspected SIH that underwent digital subtraction myelogram (DSM) preceded by brain MRI. DSMs were evaluated for the presence or absence of a CSF leak, categorized both as positive/negative/indeterminate and single versus multifocal. Brain MRIs were assessed for intracranial sequelae of SIH based on two probabilistic scoring systems (Dobrocky and Mayo methods). For each system, both an absolute “numerical” score (based on tabulation of findings) and “categorized” score (classification of probability) were tabulated. Results 174 patients were included; 113 (64.9%) were female, average age 52.0 ± 14.3 years. One or more definite leaks were noted in 76 (43.7%) patients; an indeterminate leak was noted in 22 (12.6%) patients. 16 (16.3%) had multiple leaks. There was no significant difference in the severity of intracranial findings between patients with a single versus multiple leaks ( p values ranged from .36 to .70 using categorized scores and 0.22–0.99 for numerical scores). Definite leaks were more likely to have both higher categorized intracranial scores (Mayo p = .0008, Dobrocky p = .006) and numerical scores ( p = .0002 for Mayo and p = .006 for Dobrocky). Conclusions Certainty of a CSF leak on diagnostic imaging is associated with severity of intracranial sequelae of SIH, with definite leaks having significantly more intracranial findings than indeterminate leaks. Multifocal leaks do not cause greater intracranial abnormalities.

Abstract In the last two decades, colorectal cancer (CRC) mortality has been decreasing in the United States. However, the mortality trends for the different subtypes of CRC, including different sides of colon, rectosigmoid, and rectal cancer remain unclear. We analyzed the mortality trends of different subtypes of CRC based on Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research data from 1999 to 2020. We calculated age‐adjusted mortality rates (AAMR) per 100,000 individuals and examined the trends over time by estimating the average annual percent change (AAPC) using the Joinpoint Regression Program. Our study shows that the overall CRC rates decreased significantly from 26.42 to 15.98 per 100,000 individuals, with an AAPC of −2.41. However, the AAMR of rectosigmoid cancer increased significantly from 0.82 to 1.08 per 100,000 individuals, with the AAPC of +1.10. Men and Black individuals had the highest AAMRs respectively (23.90 vs. 26.93 per 100,000 individuals). The overall AAMR of CRC decreased for those aged ≥50 years but increased significantly from 1.02 to 1.58 per 100,000 individuals for those aged 15–49 years, with an AAPC of +0.75. Rural populations had a higher AAMR than the urban populations (22.40 vs. 19.60 per 100,000 individuals). Although overall CRC mortality declined, rising trends in young‐onset CRC and rectosigmoid cancer warrant attention. Disparities persist in terms of sex, race, and geographic region, and urbanization level, emphasizing the need for targeted public health measures.

AbstractBackgroundFor many patients with lung disease the only proven intervention to improve survival and quality of life is lung transplantation (LTx). Esophageal dysmotility and gastroesophageal reflux (GER) are common in patients with respiratory disease, and often associate with worse prognosis following LTx. Which, if any patients, should be excluded from LTx based on esophageal concerns remains unclear. Our aim was to understand the effect of LTx on esophageal motility diagnosis and examine how this and the other physiological and mechanical factors relate to GER and clearance of boluses swallowed.MethodsWe prospectively recruited 62 patients with restrictive (RLD) and obstructive (OLD) lung disease (aged 33–75 years; 42 men) who underwent high resolution impedance manometry and 24‐h pH‐impedance before and after LTx.Key ResultsRLD patients with normal motility were more likely to remain normal (p = 0.02), or if having abnormal motility to change to normal (p = 0.07) post‐LTx than OLD patients. Esophageal length (EL) was greater in OLD than RLD patients' pre‐LTx (p < 0.001), reducing only in OLD patients' post‐LTx (p = 0.02). Reduced EL post‐LTx associated with greater contractile reserve (r = 0.735; p = 0.01) and increased likelihood of motility normalization (p = 0.10). Clearance of reflux improved (p = 0.01) and associated with increased mean nocturnal baseline impedance (p < 0.001) in RLD but not OLD. Peristaltic breaks and thoraco‐abdominal pressure gradient impact both esophageal clearance of reflux and boluses swallowed (p < 0.05).Conclusions and InferencesRLD patients are more likely to show improvement in esophageal motility than OLD patients post‐LTx. However, the effect on GER is more difficult to predict and requires other GI, anatomical and pulmonary factors to be taken into consideration.

Abstract Objective To develop a natural language processing (NLP) algorithm that can accurately extract headache frequency from free‐text clinical notes. Background Headache frequency, defined as the number of days with any headache in a month (or 4 weeks), remains a key parameter in the evaluation of treatment response to migraine preventive medications. However, due to the variations and inconsistencies in documentation by clinicians, significant challenges exist to accurately extract headache frequency from the electronic health record (EHR) by traditional NLP algorithms. Methods This was a retrospective cross‐sectional study with patients identified from two tertiary headache referral centers, Mayo Clinic Arizona and Mayo Clinic Rochester. All neurology consultation notes written by 15 specialized clinicians (11 headache specialists and 4 nurse practitioners) between 2012 and 2022 were extracted and 1915 notes were used for model fine‐tuning (90%) and testing (10%). We employed four different NLP frameworks: (1) ClinicalBERT (Bidirectional Encoder Representations from Transformers) regression model, (2) Generative Pre‐Trained Transformer‐2 (GPT‐2) Question Answering (QA) model zero‐shot, (3) GPT‐2 QA model few‐shot training fine‐tuned on clinical notes, and (4) GPT‐2 generative model few‐shot training fine‐tuned on clinical notes to generate the answer by considering the context of included text. Results The mean (standard deviation) headache frequency of our training and testing datasets were 13.4 (10.9) and 14.4 (11.2), respectively. The GPT‐2 generative model was the best‐performing model with an accuracy of 0.92 (0.91, 0.93, 95% confidence interval [CI]) and R 2 score of 0.89 (0.87, 0.90, 95% CI), and all GPT‐2–based models outperformed the ClinicalBERT model in terms of exact matching accuracy. Although the ClinicalBERT regression model had the lowest accuracy of 0.27 (0.26, 0.28), it demonstrated a high R 2 score of 0.88 (0.85, 0.89), suggesting the ClinicalBERT model can reasonably predict the headache frequency within a range of ≤ ± 3 days, and the R 2 score was higher than the GPT‐2 QA zero‐shot model or GPT‐2 QA model few‐shot training fine‐tuned model. Conclusion We developed a robust information extraction model based on a state‐of‐the‐art large language model, a GPT‐2 generative model that can extract headache frequency from EHR free‐text clinical notes with high accuracy and R 2 score. It overcame several challenges related to different ways clinicians document headache frequency that were not easily achieved by traditional NLP models. We also showed that GPT‐2–based frameworks outperformed ClinicalBERT in terms of accuracy in extracting headache frequency from clinical notes. To facilitate research in the field, we released the GPT‐2 generative model and inference code with open‐source license of community use in GitHub. Additional fine‐tuning of the algorithm might be required when applied to different health‐care systems for various clinical use cases.

AbstractBackgroundDespite the established efficacy of achalasia treatments on symptomatic outcomes, there are limited data evaluating the treatment effect on esophageal dilatation. This study aimed to assess the effect achalasia treatment on esophageal dilatation and the effect of esophageal width reduction (“recoil”) on clinical outcomes.MethodsPatients with type I or type II achalasia that completed high‐resolution manometry (HRM), functional lumen imaging probe (FLIP), and timed barium esophagram (TBE) pre and post treatment were included. Esophageal width was measured using TBE. Focused subgroup analysis was performed on patients with normal posttreatment EGJ opening on FLIP. Good clinical outcomes were defined as barium column height of <5 cm at 5 min and Eckardt Score ≤3.Key ResultsSixty‐nine patients (41% type I and 59% type II) were included. Esophageal width decreased from pre to post treatment mean (SD) 4.2 (1.3) cm–2.8 (1.2) cm; p < 0.01. In the normal post treatment EGJ opening subgroup, esophageal width was less in patients with good TBE outcome compared to poor outcome mean (SD) 2.2 (0.7) cm versus 3.2 (1.4) cm (p < 0.01), but did not differ in good versus poor symptomatic outcome groups. Esophageal width recoil >25% posttreatment was associated with a greater rate of good TBE outcome (71% vs. 50%, p = 0.04) and good symptomatic outcome (88% vs. 50%; p = 0.04).Conclusions and InferencesEsophageal recoil was associated with good achalasia treatment outcome in patients without posttreatment EGJ obstruction. This suggests that mechanical properties of the esophageal wall, likely associated with tissue remodeling, play a role in clinical outcomes following achalasia treatment.

Background The varicella-zoster virus (VZV), belonging to the group of human α-herpesviruses, has yet to be developed as a platform for oncolytic virotherapy, despite indications from clinical case reports suggesting a potential association between VZV infection and cancer remission. Methods Here, we constructed oncolytic VZV candidates based on the vaccine strain vOka and the laboratory strain Ellen. These newly engineered viruses were subsequently assessed for their oncolytic properties in the human MeWo melanoma xenograft model and the mouse B16-F10-nectin1 melanoma syngeneic model. Results In the MeWo xenograft model, both vOka and Ellen exhibited potent antitumor efficacy. However, it was observed that introducing a hyperfusogenic mutation into glycoprotein B led to a reduction in VZV’s effectiveness. Notably, the deletion of ORF8 (encodes viral deoxyuridine triphosphatase) attenuated the replication of VZV both in vitro and in vivo, but it did not compromise VZV’s oncolytic potency. We further armed the VZV Ellen-ΔORF8 vector with a tet-off controlled mouse single-chain IL12 (scIL12) gene cassette. This augmented virus was validated for its oncolytic activity and triggered systemic antitumor immune responses in the immunocompetent B16-F10-nectin1 model. Conclusions These findings highlight the potential of using Ellen-ΔORF8-tet-off-scIL12 as a novel VZV-based oncolytic virotherapy.