Category: Nevin Manimala

Angiogenesis. 2023 Mar 18. doi: 10.1007/s10456-023-09870-z. Online ahead of print.

ABSTRACT

The molecular mechanisms of angiogenesis have been intensely studied, but many genes that control endothelial behavior and fate still need to be described. Here, we characterize the role of Apold1 (Apolipoprotein L domain containing 1) in angiogenesis in vivo and in vitro. Single-cell analyses reveal that – across tissues – the expression of Apold1 is restricted to the vasculature and that Apold1 expression in endothelial cells (ECs) is highly sensitive to environmental factors. Using Apold1^-/- mice, we find that Apold1 is dispensable for development and does not affect postnatal retinal angiogenesis nor alters the vascular network in adult brain and muscle. However, when exposed to ischemic conditions following photothrombotic stroke as well as femoral artery ligation, Apold1^-/- mice display dramatic impairments in recovery and revascularization. We also find that human tumor endothelial cells express strikingly higher levels of Apold1 and that Apold1 deletion in mice stunts the growth of subcutaneous B16 melanoma tumors, which have smaller and poorly perfused vessels. Mechanistically, Apold1 is activated in ECs upon growth factor stimulation as well as in hypoxia, and Apold1 intrinsically controls EC proliferation but not migration. Our data demonstrate that Apold1 is a key regulator of angiogenesis in pathological settings, whereas it does not affect developmental angiogenesis, thus making it a promising candidate for clinical investigation.

PMID:36933174 | DOI:10.1007/s10456-023-09870-z

Drugs Real World Outcomes. 2023 Mar 18. doi: 10.1007/s40801-023-00360-8. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiac glycosides such as digoxin, digitoxin and ouabain are still used around the world to treat patients with chronic heart failure with reduced ejection fraction (HFrEF) and/or atrial fibrillation (AF). However, in the US, only digoxin is licensed for treating these illnesses, and the use of digoxin for this group of patients is increasingly being replaced in the US by a new standard of care with groups of more expensive drugs. However, ouabain and digitoxin, and less potently digoxin, have also recently been reported to inhibit SARS-CoV-2 virus penetration into human lung cells, thus blocking COVID-19 infection. COVID-19 is known to be a more aggressive disease in patients with cardiac comorbidities, including heart failure.

OBJECTIVE: We therefore considered the possibility that digoxin might provide at least a measure of relief from COVID-19 in digoxin-treated heart failure patients. To this end, we hypothesized that treatment with digoxin rather than standard of care might equivalently protect heart failure patients with regard to diagnosis of COVID-19, hospitalization and death.

METHODS: To test this hypothesis, we conducted a cross-sectional study by using the US Military Health System (MHS) Data Repository to identify all MHS TRICARE Prime and Plus beneficiaries aged 18-64 years with a heart failure (HF) diagnosis during the period April 2020 to August 2021. In the MHS, all patients receive equal, optimal care without regard to rank or ethnicity. Analyses included descriptive statistics on patient demographics and clinical characteristics, and logistic regressions to determine likelihood of digoxin use.

RESULTS: We identified 14,044 beneficiaries with heart failure in the MHS during the study period. Of these, 496 were treated with digoxin. However, we found that both digoxin-treated and standard-of-care groups were equivalently protected from COVID-19. We also noted that younger active duty service members and their dependents with HF were less likely to receive digoxin compared with older, retired beneficiaries with more comorbidities.

CONCLUSION: The hypothesis of equivalent protection by digoxin treatment of HF patients in terms of susceptibility to COVID-19 infection appears to be supported by the data.

PMID:36933173 | DOI:10.1007/s40801-023-00360-8

J Clin Monit Comput. 2023 Mar 18. doi: 10.1007/s10877-023-00988-5. Online ahead of print.

ABSTRACT

This study aimed to investigate the effect of preoperative education using virtual reality (VR) on preoperative anxiety and information desire. The participants were randomly assigned to the VR group and control group. The VR group received preoperative education using VR content describing preoperative and postoperative processes and their management, and the control group received preoperative education with traditional verbal education. Preoperative anxiety and information desire were measured using the Amsterdam Preoperative Anxiety and Information Scale (APAIS). Additionally, patient satisfaction was investigated. Preoperative anxiety (APAIS-A) and information desire (APAIS-I) scores were statistically significantly different between the VR group and the control group (p < 0.001). Patient satisfaction was not statistically significant (p = 0.147). Preoperative education using VR effectively reduced preoperative anxiety and information desire.Trial registration CRIS, KCT0007489. Registered 30 June 2022. http://cris.nih.go.kr/cris/ .

PMID:36933168 | DOI:10.1007/s10877-023-00988-5

Endocrine. 2023 Mar 18. doi: 10.1007/s12020-023-03341-7. Online ahead of print.

ABSTRACT

BACKGROUND: Using machine learning (ML) to explore the noninvasive differential diagnosis of Cushing’s disease (CD) and ectopic corticotropin (ACTH) secretion (EAS) model is the next hot research topic. This study was to develop and evaluate ML models for differentially diagnosing CD and EAS in ACTH-dependent Cushing’s syndrome (CS).

METHODS: Two hundred sixty-four CD and forty-seven EAS were randomly divided into training and validation and test datasets. We applied 8 ML algorithms to select the most suitable model. The diagnostic performance of the optimal model and bilateral petrosal sinus sampling (BIPSS) were compared in the same cohort.

RESULTS: Eleven adopted variables included age, gender, BMI, duration of disease, morning cortisol, serum ACTH, 24-h UFC, serum potassium, HDDST, LDDST, and MRI. After model selection, the Random Forest (RF) model had the most extraordinary diagnostic performance, with a ROC AUC of 0.976 ± 0.03, a sensitivity of 98.9% ± 4.4%, and a specificity of 87.9% ± 3.0%. The serum potassium, MRI, and serum ACTH were the top three most important features in the RF model. In the validation dataset, the RF model had an AUC of 0.932, a sensitivity of 95.0%, and a specificity of 71.4%. In the complete dataset, the ROC AUC of the RF model was 0.984 (95% CI 0.950-0.993), which was significantly higher than HDDST and LDDST (both p < 0.001). There was no significant statistical difference in the comparison of ROC AUC between the RF model and BIPSS (baseline ROC AUC 0.988 95% CI 0.983-1.000, after stimulation ROC AUC 0.992 95% CI 0.983-1.000). This diagnostic model was shared as an open-access website.

CONCLUSIONS: A machine learning-based model could be a practical noninvasive approach to distinguishing CD and EAS. The diagnostic performance might be close to BIPSS.

PMID:36933156 | DOI:10.1007/s12020-023-03341-7

Int J Colorectal Dis. 2023 Mar 18;38(1):73. doi: 10.1007/s00384-023-04353-5.

ABSTRACT

PURPOSE: Recent evidence-based publications disclosed that negative pressure wound therapy (NPWT) may reduce the incidence rate of surgical site infection (SSI) and length of stay (LOS) compared with conventional drainage in patient status post abdominoperineal resection (APR) and extralevator abdominoperineal excision (ELAPE).

METHODS: Data sources: Eligible randomized controlled trials and retrospective and prospective studies published before January 2023 were retrieved from databases (Cochrane Library, PubMed, and Embase).

STUDY SELECTION: (a) The study involved patients undergoing ELAPE or APR with postoperative NPWT; (b) the study compared NWPT with conventional drainage and reported at least one outcome of interest (i.e., SSI); and (c) the study provided adequate information to calculate the effect estimated for meta-analysis.

INTERVENTIONS: We calculated the odds ratio (ORs) and mean differences (MDs) with 95% confidence intervals (CIs).

MAIN OUTCOME MEASURES: The measure outcomes included surgical site infection(SSI) and length of stay (LOS).

RESULTS: Eight articles, involving 547 patients, met the selection criteria. Compared to conventional drainage, NPWT was associated with a significantly lower SSI rate (fixed effect, OR 0.29; 95% CI 0.18-0.45; I² = 0%) in eight studies and 547 patients. Besides, NPWT was associated with a shorter LOS (fixed effect, MD – 2.00; CI – 2.60 to – 1.39; I² = 0%) than conventional drainage in three studies and 305 patients. In a trial sequential analysis, the cumulative number of patients in the analyses of both outcomes exceeded the required information size and surpassed the significance boundary in favor of NPWT, suggesting conclusive results.

CONCLUSION: NPWT is superior to conventional drainage in both SSI rate and LOS, and the statistical power of SSI and LOS are confirmed by trial sequential analysis.

PMID:36933148 | DOI:10.1007/s00384-023-04353-5

Esophagus. 2023 Mar 18. doi: 10.1007/s10388-023-00995-0. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the performance of oropharyngoesophageal scintigraphy (OPES) in the assessment of dysphagia in patients with systemic sclerosis (SSc), and to compare OPES results with those of barium esophagogram.

METHODS: Adult SSc patients who underwent OPES for the assessment of dysphagia were enrolled. OPES was performed with both liquid and semisolid boluses and provided information regarding oropharyngeal transit time, esophageal transit time (ETT), oropharyngeal retention index (OPRI), esophageal retention index (ERI), and site of bolus retention. Barium esophagogram results were also collected.

RESULTS: Fifty-seven SSc patients (87.7% female, mean age 57.7 years) with dysphagia were enrolled. OPES identified at least one alteration in each patient and findings were generally worse for the semisolid bolus. Esophageal motility was widely impaired with 89.5% of patients with an increased semisolid ERI, and middle-lower esophagus was the most frequent site of bolus retention. However, oropharyngeal impairment was highlighted by widespread increased OPRI, especially in anti-topoisomerase I positivity. Older patients and with longer disease duration presented slower semisolid ETT (p = 0.029 and p = 0.002, respectively). Eleven patients with dysphagia had a negative barium esophagogram: all of them presented some alterations in OPES parameters.

CONCLUSION: OPES revealed a marked SSc esophageal impairment, in terms of both slowed transit time and increased bolus retention, but also shed light on oropharyngeal swallowing alterations. OPES showed high sensitivity, being able to detect swallowing alterations in dysphagic patients with negative barium esophagogram. Therefore, the use of OPES for the assessment of SSc-related dysphagia in clinical practice should be promoted.

PMID:36933137 | DOI:10.1007/s10388-023-00995-0

Environ Sci Pollut Res Int. 2023 Mar 18. doi: 10.1007/s11356-023-26451-1. Online ahead of print.

ABSTRACT

Epidemiological evidence for the relationship between cadmium exposure and mortality in specific chronic kidney disease (CKD) populations remains scarce. We aimed to explore the relationships between cadmium concentrations in urine and blood and all-cause mortality among CKD patients in the USA. This cohort study was composed of 1825 CKD participants from the National Health and Nutrition Examination Survey (NHANES) (1999-2014) who were followed up to December 31, 2015. All-cause mortality was ascertained by matching the National Death Index (NDI) records. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in relation to urinary and blood cadmium concentrations by Cox regression models. During an average follow-up period of 82 months, 576 CKD participants died. Compared with the lowest quartiles, HRs (95% CIs) for all-cause mortality associated with the fourth weighted quartiles of urinary and blood cadmium concentrations were 1.75 (1.28 to 2.39) and 1.59 (1.17 to 2.15), respectively. Furthermore, the HRs (95% CIs) for all-cause mortality per ln-transformed IQR increment in cadmium concentrations in urine (1.15 μg/g U_Cr) and blood (0.95 μg/L) were 1.40 (1.21 to 1.63) and 1.22 (1.07 to 1.40), respectively. Linear concentration-response relationships between urinary and blood cadmium concentrations and all-cause mortality were also found. Our findings suggested that increased cadmium concentrations in both urine and blood significantly contributed to enhanced mortality risk in CKD patients, thus highlighting that efforts to reduce cadmium exposure may reduce mortality risk in high-risk populations with CKD.

PMID:36933131 | DOI:10.1007/s11356-023-26451-1

Jpn J Ophthalmol. 2023 Mar 18. doi: 10.1007/s10384-023-00982-z. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the intereye correlations between and differences in the rates of visual field (VF) progression in eyes with bilateral open-angle glaucoma.

STUDY DESIGN: Retrospective, longitudinal, observational study.

METHODS: Patients with bilateral open-angle glaucoma with 8 or more reliable 30 – 2 standard automated perimetry tests over a period of more than 2 years were enrolled. The rate of change of the MD (MD slope) was used as the indicator for the rates of VF progression. Descriptive statistics of the absolute intereye difference in the MD slope values were computed. Factors associated with a large intereye difference (> 0.42 dB/year) were explored.

RESULTS: One hundred eighty-eight eyes from 94 patients (56 women) were enrolled. A significant intereye correlation of the rates of visual field progression (P = .002) was found. The mean ± standard deviation and median intereye differences of the MD slope values were 0.29 ± 0.31 and 0.18 dB/year (range: 0-1.41), respectively. The 5th, 10th, 25th, 75th, 90th, and 95th percentiles of intereye differences were 0.01, 0.02, 0.08, 0.42, 0.72, and 0.91 dB/year, respectively. Older age and slower progression were significantly associated with large intereye difference.

CONCLUSION: A significant intereye correlation in the rate of VF progression was found in eyes with bilateral open-angle glaucoma. We showed the distributions and associated factors of intereye differences in VF progression. These data may be used for improving the estimation of rates of VF progression.

PMID:36933119 | DOI:10.1007/s10384-023-00982-z

Dig Dis Sci. 2023 Mar 18. doi: 10.1007/s10620-023-07862-z. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).

METHODS: Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs.

RESULTS: Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small (n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes.

CONCLUSIONS: There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection.

PMID:36933112 | DOI:10.1007/s10620-023-07862-z

Clin Oral Investig. 2023 Mar 18. doi: 10.1007/s00784-023-04941-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the thermocycling effect of 3D-printed resins on flexural strength, surface roughness, microbiological adhesion, and porosity.

MATERIALS AND METHODS: 150 bars (8 × 2 × 2 mm) and 100 blocks (8 × 8 × 2 mm) were made and divided into 5 groups, according to two factors: “material” (AR: acrylic resin, CR: composite resin, BIS: bis-acryl resin, CAD: CAD/CAM resin, and PRINT: 3D-printed resin) and “aging” (non-aged and aged – TC). Half of them were subjected to thermocycling (10,000 cycles). The bars were subjected to mini-flexural strength (σ) test (1 mm/min). All the blocks were subjected to roughness analysis (R_a/R_q/R_z). The non-aged blocks were subjected to porosity analysis (micro-CT; n = 5) and fungal adherence (n = 10). Data were statistically analyzed (one-way ANOVA, two-way ANOVA; Tukey’s test, α = 0.05).

RESULTS: For σ, “material” and “aging” factors were statistically significant (p < 0.0001). The BIS (118.23 ± 16.26^A) presented a higher σ and the PRINT group (49.87 ± 7.55^E) had the lowest mean σ. All groups showed a decrease in σ after TC, except for PRINT. The CR_TC showed the lowest Weibull modulus. The AR showed higher roughness than BIS. Porosity revealed that the AR (1.369%) and BIS (6.339%) presented the highest porosity, and the CAD (0.002%) had the lowest porosity. Cell adhesion was significantly different between the CR (6.81) and CAD (6.37).

CONCLUSION: Thermocycling reduced the flexural strength of most provisional materials, except for 3D-printed resin. However, it did not influence the surface roughness. The CR showed higher microbiological adherence than CAD group. The BIS group reached the highest porosity while the CAD group had the lowest values.

CLINICAL RELEVANCE: 3D-printed resins are promising materials for clinical applications because they have good mechanical properties and low fungal adhesion.

PMID:36933047 | DOI:10.1007/s00784-023-04941-3