Citations

Abstract Study Objectives Narcolepsy is associated with cardiovascular risk factors; however, the risk of new-onset cardiovascular events in this population is unknown. This real-world study evaluated the excess risk of new-onset cardiovascular events in U.S. adults with narcolepsy. Methods A retrospective cohort study using IBM MarketScan administrative claims data (2014–2019) was conducted. A narcolepsy cohort, comprising adults (≥18 years) with at least two outpatient claims containing a narcolepsy diagnosis, of which at least one was non-diagnostic, was matched to a non-narcolepsy control cohort (1:3) based on cohort entry date, age, sex, geographic region, and insurance type. The relative risk of new-onset cardiovascular events was estimated using a multivariable Cox proportional hazards model to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results The narcolepsy and matched non-narcolepsy control cohorts included 12 816 and 38 441 individuals, respectively. At baseline, cohort demographics were generally similar; however, patients with narcolepsy had more comorbidities. In adjusted analyses, the risk of new-onset cardiovascular events was higher in the narcolepsy cohort compared with the control cohort: any stroke (HR [95% CI], 1.71 [1.24, 2.34]); heart failure (1.35 [1.03, 1.76]); ischemic stroke (1.67 [1.19, 2.34]); major adverse cardiac event (1.45 [1.20, 1.74]); grouped instances of stroke, atrial fibrillation, or edema (1.48 [1.25, 1.74]); and cardiovascular disease (1.30 [1.08, 1.56]). Conclusion Individuals with narcolepsy are at increased risk of new-onset cardiovascular events compared with individuals without narcolepsy. Physicians should consider cardiovascular risk in patients with narcolepsy when weighing treatment options.

AbstractBackgroundDeformable Image Registration (DIR) is an essential technique required in many applications of radiation oncology. However, conventional DIR approaches typically take several minutes to register one pair of 3D CT images and the resulting deformable vector fields (DVFs) are only specific to the pair of images used, making it less appealing for clinical application.PurposeA deep‐learning‐based DIR method using CT images is proposed for lung cancer patients to address the common drawbacks of the conventional DIR approaches and in turn can accelerate the speed of related applications, such as contour propagation, dose deformation, adaptive radiotherapy (ART), etc.MethodsA deep neural network based on VoxelMorph was developed to generate DVFs using CT images collected from 114 lung cancer patients. Two models were trained with the weighted mean absolute error (wMAE) loss and structural similarity index matrix (SSIM) loss (optional) (i.e., the MAE model and the M+S model). In total, 192 pairs of initial CT (iCT) and verification CT (vCT) were included as a training dataset and the other independent 10 pairs of CTs were included as a testing dataset. The vCTs usually were taken 2 weeks after the iCTs. The synthetic CTs (sCTs) were generated by warping the vCTs according to the DVFs generated by the pre‐trained model. The image quality of the synthetic CTs was evaluated by measuring the similarity between the iCTs and the sCTs generated by the proposed methods and the conventional DIR approaches, respectively. Per‐voxel absolute CT‐number‐difference volume histogram (CDVH) and MAE were used as the evaluation metrics. The time to generate the sCTs was also recorded and compared quantitatively. Contours were propagated using the derived DVFs and evaluated with SSIM. Forward dose calculations were done on the sCTs and the corresponding iCTs. Dose volume histograms (DVHs) were generated based on dose distributions on both iCTs and sCTs generated by two models, respectively. The clinically relevant DVH indices were derived for comparison. The resulted dose distributions were also compared using 3D Gamma analysis with thresholds of 3 mm/3%/10% and 2 mm/2%/10%, respectively.ResultsThe two models (wMAE and M+S) achieved a speed of 263.7±163 / 265.8±190 ms and a MAE of 13.15±3.8 / 17.52±5.8 HU for the testing dataset, respectively. The average SSIM scores of 0.987±0.006 and 0.988±0.004 were achieved by the two proposed models, respectively. For both models, CDVH of a typical patient showed that less than 5% of the voxels had a per‐voxel absolute CT‐number‐difference larger than 55 HU. The dose distribution calculated based on a typical sCT showed differences of ≤2cGy[RBE] for clinical target volume (CTV) D95 and D5, within ±0.06% for total lung V5, ≤1.5cGy[RBE] for heart and esophagus Dmean, and ≤6cGy[RBE] for cord Dmax compared to the dose distribution calculated based on the iCT. The good average 3D Gamma passing rates (> 96% for 3 mm/3%/10% and > 94% for 2 mm/2%/10%, respectively) were also observed.ConclusionA deep neural network‐based DIR approach was proposed and has been shown to be reasonably accurate and efficient to register the initial CTs and verification CTs in lung cancer.

In this study, we report for the first time the in vivo emergence of dual resistance to levofloxacin and rifampin in C. avidum isolated from a patient who received both antibiotics orally in the setting of a salvage debridement and implant retention of an ODRI. Aside from the molecular insights reported here, this study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing these surgical procedures and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens.

AbstractBackgroundObtaining a diagnosis and treating pulmonary malignancies during the same anesthesia requires either an on‐site pathologist or a system for remotely evaluating microscopic images. Cytology specimens are challenging to remotely assess given the need to navigate through dispersed and three‐dimensional cell clusters. Remote navigation is possible using robotic telepathology, but data are limited on the ease of use of current systems, particularly for pulmonary cytology.MethodsAir dried modified Wright‐Giemsa stained slides from 26 touch preparations of transbronchial biopsies and 27 smears of endobronchial ultrasound guided fine needle aspirations were scored for ease of adequacy assessment and ease of diagnosis on robotic (rmtConnect Microscope) and non‐robotic telecytology platforms. Diagnostic classifications were compared between glass slides and the robotic and non‐robotic telecytology assessments.ResultsCompared to non‐robotic telecytology, robotic telecytology had a greater ease of adequacy assessment and non‐inferior ease of diagnosis. The median time to diagnosis using robotic telecytology was 85 s (range 28–190 s). Diagnostic categories were concordant for 76% of cases in robotic versus non‐robotic telecytology and 78% of cases in robotic telecytology versus glass slide diagnosis. Weighted Cohen's kappa scores for agreement in these comparisons were 0.84 and 0.72, respectively.ConclusionsUse of a remote‐controlled robotic microscope improved the ease of adequacy assessment compared to non‐robotic telecytology and enabled strongly concordant diagnoses to be expediently rendered. This study provides evidence that modern robotic telecytology is a feasible and user‐friendly method of remotely and potentially intraoperatively rendering adequacy assessments and diagnoses on bronchoscopic cytology specimens.

Hyperuricemia is described as a serum uric acid level more than 6.0 mg/dL. It is demonstrated by basic research and clinical studies, which the elevation of uric acid level may change the renal histology and function by developing acute and chronic kidney diseases (CKDs), diabetic nephropathy and end-stage renal disease (ESRD). There is no doubt about a significant relationship between uric acid and renal impairment. However, the details of this correlation, especially; between uric acid and renal failure, are discussable. Renal vasoconstriction, antiangiogenic properties, endothelial dysfunction, proinflammatory properties, renal fibrosis, pro-oxidative properties, and alteration of renal autoregulation are the most common mechanisms, which approve the association between uric acid and renal impairment. Allopurinol administration for CKD treatment in patients with gout is one of the most discussable challenges. It should be investigated whether allopurinol can diminish the deterioration of the glomerular filtration rate (GFR) in CKD patients who are at risk of ESRD. Some previous studies reported that allopurinol decreases the CKD incident risk, but others could not confirm this association. The benefit or risks of allopurinol in different stages of CKD, dialysis, and renal transplant are discussed in this study.

ABSTRACT Snapping proximal hamstring is an uncommon phenomenon, with few case reports documenting surgical treatment. The purpose of this study is to report snapping resolution, minimum 2-year post-operative patient-reported outcome (PRO), satisfaction scores and complications from patients who underwent surgical release of the conjoint tendon from the sacrotuberous ligament with reattachment to the ischial tuberosity. Prospectively collected data from two institutional databases were retrospectively reviewed for patients who underwent hamstring repair for partial- or full-thickness tears. Patients were included if they demonstrated ‘snapping proximal hamstrings’ on preoperative physical examination, including ultrasound confirmation, and repair subsequently performed. Patients were excluded if they had reconstruction of the proximal hamstring tendon or claimed worker’s compensation. With a total of 20 patients (15 females and 5 males), successful resolution of snapping was reported in 100% of the cohort. For patients with pre- and post-surgical lower-extremity functional scores (LEFS), post-surgical LEFS were significantly higher than pre-surgical LEFS (pre-surgical: 17.0 ± 4.0, post-surgical: 73.6 ± 3.3, P < 0.001). Average post-operative PROs were as follows: International Hip Outcome Tool-12, 92.3 ± 8.3; modified Harris Hip Score, 93.2 ± 7.8; Non-arthritic Hip Score, 92.5 ± 6.8; Hip Outcome Score-Sports Specific Subscale, 94.4 ± 6.7; LEFS, 73.9 ± 3.4; and median visual analog scale of 0 with an interquartile range of 0-1. Patient satisfaction was ‘very satisfied’ in 19 (95%) patients and ‘satisfied’ in 1 (5%) patient. At a minimum 2-year follow-up, patients who underwent surgical treatment for chronic snapping of the proximal hamstrings demonstrated complete resolution of painful posterior snapping, reported high PROs and satisfaction, and had no reported post-operative complications.

Objective: Limited evidence is available regarding the impact of workload-indexed hypertensive response to exercise (HRE) in patients at different stages of the heart failure (HF) spectrum. We evaluated the prevalence, pathophysiologic and prognostic correlates of HRE, evaluated by the systolic blood pressure (SBP)/Workload slope, across the HF spectrum as defined by the American College of Cardiology/American Heart Association. Design and method: We prospectively enrolled 58 healthy controls, 201 subjects at risk of developing HF (HF Stages A-B), and 369 patients with a definite diagnosis of HF (Stage C) and either preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction. All patients underwent a combined cardiopulmonary-exercise stress echocardiography test. We recorded two SBP measurements for each patient: the first within the first minute of exercise and the last at peak effort. The SBP/Workload slope was calculated as the difference in SBP over the corresponding increment in watts (W): (SBPpeak – SBPfirst)/(Wpeak – Wfirst). In each subgroup, we divided patients according to SBP/Workload slope tertiles, using sex-specific cut-off values; HRE was defined as the highest SBP/Workload slope tertile in each HF stage. A composite of all-cause mortality and hospitalization for cardiovascular reasons was chosen as the primary outcome. Results: The median SBP/Workload slope was 0.53 (interquartile range 0.36 - 0.72) mmHg/W and was steeper in women than men in all subgroups. After adjusting for age and sex, SBP/Workload slope in controls was similar to HFrEF but significantly lower than Stages A-B and HFpEF. In all HF stages, patients with HRE showed significantly lower peak oxygen consumption and peripheral oxygen extraction. After a median follow-up of 16 months, HRE was independently associated with adverse outcomes (Hazard Ratio 2.05, 95% confidence interval 1.81 - 5.18). Kaplan-Meier analysis confirmed a worse survival probability in Stages A-B and HFpEF, but not HFrEF. After adjusting for clinical and echocardiographic variables, patients in the highest SBP/Workload tertile had a 47% higher risk of the primary outcome than subjects in the lowest tertile. Conclusions: HRE is associated with peculiar pathophysiological features and possibly worse prognosis in patients in the earliest stages of cardiovascular disease and in those with HFpEF.

Objective: Electro-Hydraulic Acoustic Therapy (eHAT), using ∼10% of the energy used in shockwave lithotripsy, is a promising technique to ameliorate ischemia and regenerate tissues. eHAT has been demonstrated to enhance healing in tissues such as bone, muscle, and myocardium, via several mechanisms, particularly by promoting neovascularization. Furthermore, previous animal studies demonstrated that eHAT reduces blood pressure (BP) and preserves renal function after ischemic kidney injury. The present pilot study explored the clinical safety and efficacy of eHAT and tested the hypothesis that eHAT would reduce BP and preserve renal function in patients with medically-treated hypertension and CKD. Design and method: So far, a total of 15 patients with HTN and Stage III a/b CKD were enrolled in this prospective, single-arm study. The patients were treated with six sessions of eHAT during a 3-week period. At each session, 2400 shockwaves were applied to each kidney with 0.09 mJ/mm2 at 2.66Hz (NephrospecTM by Curespec LTD, Yehud, Israel). Follow-up (FU) visits were performed at 1, 3, and 6 months. Results: The treatment was well tolerated with no major adverse events or need for analgesic treatment. Average Automated Office BP (AOBP) showed a strong tendency for a decrease in diastolic BP from baseline to the Primary Efficacy Objective at FU II (3 months post-last treatment), which progressively decreased further at FU III (6 months) (Table 1). Similarly, average Office BP (OBP) detected a strong trend for a progressive decrease in systolic BP from baseline to the Primary Efficacy Objective (Table 1). Levels of eGFR appeared to slightly rise throughout the study, but this change has not reached statistical significance levels (Table 1). Conclusions: The current study demonstrates that the eHAT procedure is tolerable and safe in this cohort. Moreover, a 3-week regimen tended to reduce BP and preserve eGFR in patients with controlled HTN and CKD. Therefore, electro-Hydraulic Acoustic Therapy may emerge as a novel, safe, and non-invasive alternative therapeutic approach in the management of HTN in the context of CKD.

Abstract Aims Current European heart failure (HF) guidelines suggest the use of risk score: among them, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has demonstrated to be one of the most accurate. However, the risk scores are still poorly implemented in clinical practice, also due to the lack of strong evidence regarding their external validation in different populations. Thus, the current study was designed as an external validation test of the MECKI score in an international multicentre setting. Methods and results The study cohort consisted of patients diagnosed with HF with reduced ejection fraction (HFrEF) across international centres (not Italian), retrospectively recruited. Collected data included demographics, HF aetiology, laboratory testing, electrocardiogram (ECG), echocardiographic findings, and cardiopulmonary exercise testing (CPET) results as described in the original MECKI score publication. A total of 1042 patients across 8 international centres (7 European and 1 Asian) were included and followed up from 1998 till 2019. Patients were divided according to the calculated MECKI scores into three subgroups: (i) MECKI score <10%, (ii) 10–20%, and (iii) ≥ 20%. Survival analysis comparison among the three MECKI score subgroups showed a worse prognosis in patients with higher MECKI score value: median event-free survival times were 4396 days for MECKI score <10%, 3457 days for 10–20%, and 1022 days for ≥20% (P < 0.0001). Receiver operating characteristic (ROC) curves and area under the ROC curves (AUC) were like those reported in the original internal validation studies. Conclusion In patients diagnosed with HFrEF, the power of the MECKI score was confirmed in terms of prognosis and risk stratification, supporting its implementation as advised by the HF guidelines.

Abstract Background This study described the clinical characteristics, outcomes, and prognosis of Crohn’s disease (CD) patients with anal cancer in a tertiary referral center. Methods The electronic medical records of 35 adult CD patients, including CD of the pouch, with anal carcinoma evaluated at Mayo Clinic Rochester, Florida, or Arizona between January 1989 and August 2022 were retrospectively reviewed. Results Before cancer diagnosis, patients with pouch-related carcinoma had a shorter median duration of inflammatory bowel disease than those with anal carcinoma (10 vs 26 years). Twenty-six patients (74%) had perianal diseases or rectovaginal fistula, and 35% had a history of human papillomavirus infection. Twenty-one patients (60%) were diagnosed with cancer by anal examination under anesthesia (EUA). More than half of adenocarcinomas were mucinous. Sixteen patients (47%) were American Joint Committee on Cancer (AJCC) Tumor Nodes Metastasis (TNM) stage 3, and 83% were treated by surgery. At last follow-up, 57% of patients were alive without cancer. The 1-, 3- and 5-year overall survival rates were 93.8% (95% confidence interval [CI], 85.7%-100%), 71.5% (95% CI, 56.4%-90.7%), and 67.7% (95% CI, 51.2%-87.7%), respectively. Advanced AJCC TNM stage (hazard ratio, 3.20 per stage; 95% CI, 1.05-9.72; P = .040) was significantly associated with increased risk of death, whereas the period of cancer diagnosis in 2011-2022 (HR, relative to 1989-2000, 0.16; 95% CI, 0.04-0.72; P = .017) was significantly related to decreased risk of death. Conclusions Anal and pouch-related carcinomas were rare complications of CD, and long-standing perianal diseases were an important risk factor. Anal EUA improved the diagnostic yield. Newer cancer treatment strategies and surgery were associated with excellent survival outcome.