Chicago Classification Version 4.0 Improves Stratification of Ineffective Esophageal Motility Patients into Clinically Meaningful Subtypes: A Two-Center International Study.

The 4th iteration of the Chicago Classification (CC v4.0) for esophageal motility disorders offers more restrictive criteria for the diagnosis of Ineffective Esophageal Motility (IEM) compared to version 3.0 (CC v3.0). In light of the updated criteria for IEM, we aimed to characterize and compare the patients who retained their IEM diagnosis to those who were reclassified as normal motility, and to evaluate the clinical impact of the newly introduced CC v4.0. We performed a retrospective case-control study. We included all individuals who underwent a high-resolution manometry (HRM) between 2020 and 2021 at two centers. Consecutive studies reported as IEM according to the CC v3.0 were reanalyzed according to the CC v4.0. We compared demographics, clinical, manometry, and pH-monitoring parameters. Out of 452 manometry studies, 154 (34%) met criteria for IEM as per the CC v3.0 (CC v3.0 IEM group). Of those, 39 (25%) studies were reclassified as normal studies according to the CC v4.0 (CC v4.0 normal group), while the remaining 115 studies (25% of the overall cohort) retained an IEM diagnosis (CC v4.0 IEM group). The CC v4.0 normal group had more recovered contractions during solid swallows (p = 0.01), less ineffective swallows (p = 0.04), and lower acid exposure time (p = 0.02) compared to the CC4.0 IEM group. Under CC v4.0 criteria, fewer patients are diagnosed with IEM. Those diagnosed with IEM had worse esophageal function and higher acid burden. Though further studies are needed to confirm these findings, our results indicate that CC v4.0 criteria restrict the IEM diagnosis to a more clinically meaningful population.

Correlation between Lower Esophageal Sphincter Metrics on High-Resolution Manometry and the Clinical Presentation of Patients with Newly Diagnosed Achalasia.

BACKGROUND: Achalasia is characterized by aperistalsis with poor relaxation of the lower esophageal sphincter (LES). We aimed to systematically assess whether LES metrics on high-resolution manometry (HRM) correlate with the symptomatic or endoscopic presentation of patients with achalasia. METHODS: A retrospective study was performed at two tertiary medical centers. All cases of newly diagnosed, untreated achalasia were reviewed for demographics, symptoms, and endoscopic findings. These were correlated with HRM metrics, including LES basal pressure (LESP), integrated relaxation pressure (IRP), percent LES relaxation, and esophagogastric junction (EGJ) morphology. RESULTS: 108 achalasia patients were included; 56 (51.9%) were men, with a mean overall age of 55.6 ± 17.9 years old. Achalasia subtypes included 23.1% with Type I, 65.7% Type II, and 11.1% Type III. Mean LESP was 40.9 ± 13.7 mmHg, IRP 26.8 ± 11.5 mmHg, with 36% ± 20% LES relaxation. On univariate analyses, a higher IRP was associated with age < 50 (p = 0.028), female sex (p = 0.030), Arab ethnicity (p < 0.001), weight loss (p = 0.016), a tortuous esophagus (p = 0.036), and resistance at the EGJ (p = 0.033). However, on multivariate regression analyses, only ethnicity remained significantly associated with IRP. No unique variables were associated with either LESP or percent LES relaxation. Achalasia subtype and Eckardt score were not associated with any LES metrics. Non-Type 1 EGJ morphology was associated with a lower LESP. CONCLUSIONS: LES metrics on HRM do not appear to correlate with the clinical or endoscopic presentation of patients with untreated achalasia.

Ethnic Differences in Clinical Presentations and Esophageal High-Resolution Manometry Findings in Patients with Achalasia.

BACKGROUND: Ethnic differences in achalasia presentations have scarcely been described. The association between achalasia and immunologic HLA haplotypes suggests that there may be a genetic predisposition. We aimed to evaluate differences in demographic, clinical, endoscopic, and manometric findings between two distinct ethnic groups with achalasia-Israeli Arabs (IA) and Israeli Jews (IJ). METHODS: A retrospective study was performed at two medical centers. High-resolution manometry (HRM) reports were reviewed for newly-diagnosed achalasia patients. Demographic data, clinical presentations, endoscopy reports, and HRM metrics including the integrated relaxation pressure (IRP) were all reviewed. RESULTS: Overall, 94 achalasia patients were included (53.2% male; mean age 54.5 ± 18.0). 43 patients were IA (45.7%). Body mass index (BMI) was similar in both groups. Compared to IJ, the IA patients had more esophageal dysphagia (100% vs. 88.2%; P = 0.022), chest pain (46.5% vs. 25.5%; P = 0.033), and a tortuous esophagus on endoscopy (23.3% vs. 3.9%; p = 0.005). IA patients were also diagnosed at a younger age than IJ patients (50.9 ± 17.5 vs. 57.5 ± 18.0; p = 0.039). Furthermore, IRP values were higher among IA patients than IJ patients (32.2 ± 13.8 vs. 23.3 ± 8.4; p < 0.001). A regression model analysis found that ethnicity significantly predicted IRP (ß = - 10, p < .001). CONCLUSION: Ethnicity appears to affect achalasia clinical presentation and HRM findings. IA achalasia patients are diagnosed at a younger age, present with more severe esophageal symptoms, and have a higher IRP compared to IJ patients. Additional studies of diverse, multiethnic populations, especially with genetic evaluations, are required to further assess the role of ethnicity in achalasia.

The short term adaptation of the autonomic nervous systems (ANS) by type of urban environment and ethnicity.

BACKGROUND: Previous studies examined the effects of urban environments on the Autonomic Nervous System (ANS). These studies measured the effects of environments on Heart Rate Variability (HRV) averaging different time intervals to one value. Yet, the dynamics of change, reflecting the functions and their derivatives that describe the adaptation to the new environments remain unknown. In addition, ethnic differences in the ANS adaptation were not investigated. METHOD: Forty-eight Arab and 24 Jewish women ages 20-35 years, all healthy, non-smokers were recruited by a snowball sample. Both groups were of a similar socioeconomic status and BMI distributions. Using a portable monitor, the HRV response was continuously analyzed for 35 min of sedentary sitting in each of the three environments: a park, a city center and a residential area. LF/HF polynomial function was adapted to describe the dynamic change in each environment for each ethnic group. RESULTS: Green area exposure was associated with 90% immediate change while in built-up areas, the change in HRV is about 40% adaptive (changing gradually). The adaptive process of HRV may stabilize after 15 min in the city center yet not even after 35 min in the residential environment. The total change (immediate + adaptive) reached 24% in city centers and 10% in residential areas. Changes in HRV rates in the park and the city center environments were higher among Arab women as compared to Jewish women but similar between the two groups in the residential area. The distributions of LF/HF in each time cohort were normal, meaning that shifting the focus to analyze functions of change in HRV, opens the possibility to employ analytic methods that assume the normal distribution. CONCLUSIONS: Changing the focus from average levels of HRV to functions of change and their derivatives brings new insight into the understanding of the ANS response to environmental challenges. ANS short term adaptation to different environments is gradual and spans differently both in magnitude of response and latencies between different environments. Importantly, in green areas, the response is immediate unlike the adaptation to urban environments that is significantly more gradual. The ethnic differences in ANS adaptation is also noteworthy. In addition, adaptation proceeesses are normaly distributed in each time cohort suggesting a possible novel ANS index.

Women Emotional, Cognitive and Physiological Modes of Coping with Daily Urban Environments: A Pilot Study.

Studies on the effect of urban environments on human risk to health and well-being tend to focus on either physiological or cognitive and emotional effects. For each of these effects, several indicators have been proposed. They are determined either by a physiological-emotional theory or by a cognitive theory of direct attention. However, the interrelationships between these indices have not been thoroughly investigated in environmental contexts. Recently, a neuro-visceral model that incorporates all three aspects has been proposed. The present article focuses on understanding the mechanism of coping with urban environments. More specifically, we analyze the interrelations among nine of the more commonly used indices that represent the physiological, emotional and cognitive aspects of coping with urban environments. The data were collected in the following four environments: home, park, city center and residential area. The participants were 72 healthy, middle-class mothers with either high school or postgraduate education. They wherein their fertile age (20-35) with average Body Mass Index (BMI) of 22.2 and S.D. of 0.8 (48 Arab Muslims and 24 Jewish). They were recruited in a snowball method. Path analysis and principal component analysis are used in order to identify the interrelations among the physiological, cognitive and emotional indices and the directions of these interrelations. According to the findings, the Autonomic Nervous System (ANS), as measured by Heart Rate Variability (HRV) and primarily the parasympathetic tone (High frequency-HF) is the pivotal mechanism that modulates emotional and cognitive responses to environmental nuisances. The ANS response precedes and may trigger the emotional and the cognitive responses, which are only partially interrelated. It appears that the autonomic balance measured by Standard Deviation of NN interval (SDNN) and HF, the cognitive index of restoration and the emotional indices of discomfort and relaxation are closely interrelated. These seemingly disparate operands work together to form a comprehensive underlying network that apparently causes stress and risk to health in urban environments while restoring health in green environments.

An Innovative Ultrasound Technique for Early Detection of Kidney Dysfunction: Superb Microvascular Imaging as a Reference Standard.

BACKGROUND: Superb microvascular imaging (SMI) is an innovative ultrasound image processing technique that provides greater detail and better visualization of small branching vessels. We assume that SMI will provide sufficient information regarding the severity of chronic kidney disease (CKD) and reflecting histological changes. AIMS: The aims was to assess the capabilities of SMI imaging regarding the early detection of kidney dysfunction and renal fibrosis in comparison to the reference standard renal biopsy for the early diagnosis of kidney fibrosis. METHODS: SMI was performed in patients (n = 52) with CKD stage 2-5, where some of them underwent biopsy proven CKD and fibrosis as part of the diagnosis. In addition, biochemical tests were performed, including kidney function tests, urine collection for proteinuria, and the estimation of GFR by MDRD or CKD-EPI eGFR in CKD patients and healthy controls (n = 17). All subjects underwent SMI, where vascularity is expressed as the SMI index (a low index reflects low vascularity/fibrosis and vice versa). RESULTS: The SMI vascular index was significantly lower in CKD patients as compared with healthy controls (72.2 ± 12.9 vs. 49.9 ± 16.7%, p < 0.01). Notably, a moderate correlation between the SMI index and eGFR was found among the CKD patients (r = 0.56, p < 0.001). Similarly, a strong correlation was found between SCr and the SMI index of the diseased subjects (r = -0.54, p < 0.001). In patients who underwent renal biopsy, the SMI index corresponded with the histological alterations and CKD staging. CONCLUSIONS: This study demonstrated that SMI imaging may be utilized in CKD patients of various stages for the evaluation of chronic renal morphological changes and for differentiation between CKD grades.

HIV Viremia Is Associated With APOL1 Variants and Reduced JC-Viruria.

Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89-40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49-13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0-5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66-33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12-0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.

Effects of Preoperative WBC Count on Post-CABG Surgery Clinical Outcome.

OBJECTIVE: White blood cells (WBCs) play a major role in inflammation, with effects on the vascular wall, the microvascular blood flow, and endothelial cells and endothelial function. Previous studies have shown that a high WBC count may increase the risk of cardiovascular complication rate and mortality after coronary artery bypass graft (CABG) surgery. The aim of the study was to evaluate the association between preoperative WBC count and the post-CABG clinical outcome. METHODS: A retrospective study that was based on 239 patients who underwent CABG surgery in our medical center. Statistical analysis estimated the effect of WBC count in postoperative clinical outcomes, including atrial fibrillation, length of stay, readmission rate, and death. RESULTS: The preoperative WBC count was associated with longer hospitalization length (B = 0.392, P < 0.01). A preoperative WBC count >8150/µL predicted a longer stay (Z = 2.090, P = 0.03). A low lymphocyte count was associated with atrial fibrillation (B = -0.543, P = 0.03). Female patients were older (Z = 2.920, P < 0.01), had impaired renal function (Z = -3.340, P < 0.01), and had a higher rate of postoperative atrial fibrillation (df 2 = 3.780, P = 0.05) and readmission (df 2 = 5.320, P = 0.02). CONCLUSIONS: Preoperative WBC count may have an effect on the postoperative clinical outcome in patients undergoing CABG. Surgeons should pay more attention to patients' WBC count and sex and plan surgery and postoperative management accordingly.

Diagonal Earlobe Crease (Frank's Sign): A Predictor of Cerebral Vascular Events.

BACKGROUND: Frank's sign was first described in 1973 by an American physician (Sonders T. Frank). It is a diagonal crease in the earlobe that starts from the tragus to the edge of the auricle in an angle of 45° in varying depths. Frank's sign was described as a predictor of future coronary heart disease and peripheral vascular diseases. The aim of the study was to examine the association between Frank's sign and the development of ischemic stroke. METHODS: This was a prospective study that enrolled consecutive patients admitted with an acute ischemic stroke. Frank's sign was tested in both ears. Clinical data included age, gender, type 2 diabetes mellitus, and hypertension. The study was approved by the institutional review board (the institutional ethics committee). RESULTS: A total of 241 consecutive patients who were hospitalized with an acute stroke and were eligible to take part in the study were recruited. Frank's sign was present in 190 patients (78.8%). Patients were divided according to clinical findings and the findings from brain computed tomography. There were 153 patients with transient ischemic attacks (63.6% of the patients) and 88 with cerebrovascular accidents (36.4% of the patients). A total of 112 patients with transient ischemic attacks had Frank's sign (73.2%), and 78 patients with cerebrovascular accidents had Frank's sign (88.6%), with a statistically significant difference (P <.01). DISCUSSION: Frank's sign could predict ischemic cerebrovascular events. Patients with classical cardiovascular risk factors had Frank's sign at a higher frequency.