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Antipathogenic Efficacy of Biogenic Silver Nanoparticles and Antibiofilm Activities Against Multi-drug-Resistant ESKAPE Pathogens

Appl Biochem Biotechnol. 2023 Jul 18. doi: 10.1007/s12010-023-04630-7. Online ahead of print.

ABSTRACT

The silver nanoparticles (AgNPs) were produced by employing a biogenic loom and tested for antipathogenic assets against multi-drug-resistant (MDR) ESKAPE bacteria. Biogenically synthesized AgNPs were characterized adopting various high-throughput techniques such as UHRTEM, SEM with EDX, DLS, TGA-DTA, and XRD and spectroscopic analysis showed polydispersion of nanoparticles. In this context, AgNPs with the attribute of spherical-shaped nanoparticles with an average size of 26 nm were successfully synthesized utilizing bacterial supernatant. The antipathogenic activities of AgNPs were assessed against 11 strains of MDR ESKAPE bacteria including Enterococcus faecium; methicillin-resistant Staphylococcus aureus; Klebsiella pneumonia; Acinetobacter baumannii; Pseudomonas aeruginosa; Enterobacter aerogenes; and Enterobacter species. The exposure of biogenic AgNPs in a well diffusion assay showed all the growth inhibitions of ESKAPE bacteria at 200 μg/ml after 18 h of incubation. Growth kinetics demonstrated maximum killing at 60 μg/ml after 4 h of completion. The highest biofilm depletions were found at 100 μg/ml in adhesion assay. Live/dead assays showed effective killing of the ESKAPE bacteria at 10 μg/ml in pre-existing biofilms. The effective inhibitory concentrations of AgNPs were investigated ranging from 10 to 200 μg/ml. The selected pathogens found sensitive to AgNPs are statistically significant (P < 0.05) than that of cefotaxime/AgNO3. Consequently, a broad spectrum of antimicrobial potentials of AgNPs can be alternative to conventional antimicrobial agents for future medicine.

PMID:37462813 | DOI:10.1007/s12010-023-04630-7

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Progression pattern of non-amblyopic Anisomyopic eyes compared to Isomyopic eyes

Eur J Pediatr. 2023 Jul 18. doi: 10.1007/s00431-023-05088-9. Online ahead of print.

ABSTRACT

This study aimed to determine the progression pattern of non-amblyopic anisomyopic children from ages 6 to 16 years. This retrospective study analyzed the electronic medical records of 8680 myopic children who visited Sankara Nethralaya, Chennai, India over eight years (2009 to 2017). A total of 711 records were retrieved based on inclusion criteria. In addition, 423 records out of 711 had consecutive follow-up for three years (baseline plus three follow-up visits) and were considered to determine the progression pattern. The cycloplegic sphero-cylindrical refraction was taken for analysis and converted to vector notation of M (SE), J0, and J45. Anisomyopia referred to the interocular difference of myopic SE of ≥ 1 D whereas isomyopia referred to the interocular difference of myopic SE of < 1 D. Based on the refraction of the less ametropic eye, anisomyopes were further categorized into bilateral anisometropic myopia (BAM) and unilateral anisometropic myopia (UAM). The isomyopic cohort showed a mean annual progression of -0.49 ± 0.54 D (median [IQR] -0.38 D [{-0.75}-0.00]). In BAM, the mean annual progression of the more myopic eye was -0.45 ± 0.55 D (median [IQR] -0.38 D [{-0.75}-0.00]), and the less myopic eye was -0.37 ± 0.55 D (median [IQR] -0.25 D [{-0.63}-0.00]). This difference was significant (t (212) = -2.14, p < 0.05). In UAM, the myopic eyes (-0.39 ± 0.51 D; median [IQR] -0.25 D [{-0.75}-0.00]) showed a statistically significant higher mean annual progression compared to emmetropic eyes (-0.22 ± 0.36 D; median [IQR] 0.00 D [{-0.44}-0.00]; t (96) = -3.30, p < 0.001). In terms of progression trend, in the BAM group, the rate of change of mean SE between the more myopic and the less myopic eyes were similar (-1.12 ± 1.20 D; median [IQR] -1.13 D [{-2.00}-{-0.38}] vs. -1.05 ± 1.25 D; median [IQR] -0.88 D [{-1.75}-{-0.13}]; t (138) = -0.64, p > 0.05). However, the more myopic eyes of UAM showed a higher myopic trend compared to the emmetropic eyes (-1.37 ± 1.06 D; median [IQR] -1.32 D [{-2.13}-{-0.50}] vs. -0.96 ± 1.11 D; median [IQR] -0.75 D [{-1.56}-{-0.25}]; t (61) = -2.74, p < 0.05). Conclusion: Children with BAM and UAM eyes exhibit different progression patterns from each other. While the rate of the refractive shift in myopic eyes of UAM is similar to isomyopic eyes, BAM eyes present a slower rate of progression than isomyopic eyes. What is Known: • The rate of change of refraction in anisomyopes is higher compared to isomyopic children. • Less myopic eyes tend to shift towards more myopia while more myopic eyes show stable refraction. What is New: • The progression pattern of bilateral anisometropic myopia and unilateral anisometropic myopia differ from one another. • While the rate of the refractive shift in myopic eyes of unilateral anisometropic myopia is similar to isomyopic eyes, bilateral anisometropic myopia eyes present a slower rate of progression than isomyopic eyes. • The pattern of change in the interocular difference of anisometropia depends on the laterality (bilateral or unilateral ametropia), and degree of spherical equivalent in the more ametropic eye.

PMID:37462797 | DOI:10.1007/s00431-023-05088-9

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Novel economical, accurate, sensitive, single-cell analytical method for mitochondrial DNA quantification in mtDNA mutation carriers

J Assist Reprod Genet. 2023 Jul 18. doi: 10.1007/s10815-023-02878-w. Online ahead of print.

ABSTRACT

PURPOSE: Although a variety of analytical methods have been developed to detect mitochondrial DNA (mtDNA) heteroplasmy, there are special requirements of mtDNA heteroplasmy quantification for women carrying mtDNA mutations receiving the preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PD) in clinic. These special requirements include various sample types, large sample number, long-term follow-up, and the need for detection of single-cell from biopsied embryos. Therefore, developing an economical, accurate, high-sensitive, and single-cell analytical method for mtDNA heteroplasmy is necessary.

METHODS: In this study, we developed the Sanger sequencing combined droplet digital polymerase chain reaction (ddPCR) method for mtDNA quantification and compared the results to next-generation sequencing (NGS). A total of seventeen families with twelve mtDNA mutations were recruited in this study.

RESULTS: The results showed that both Sanger sequencing and ddPCR could be used to analyze the mtDNA heteroplasmy in single-cell samples. There was no statistically significant difference in heteroplasmy levels in common samples with high heteroplasmy (≥ 5%), low heteroplasmy (< 5%), and single-cell samples, either between Sanger sequencing and NGS methods, or between ddPCR and NGS methods (P > 0.05). However, Sanger sequencing was unable to detect extremely low heteroplasmy accurately. But even in samples with extremely low heteroplasmy (0.40% and 0.92%), ddPCR was always able to quantify them. Compared to NGS, Sanger sequencing combined ddPCR analytical methods greatly reduced the cost of sequencing.

CONCLUSIONS: In conclusion, this study successfully established an economical, accurate, sensitive, single-cell analytical method based on the Sanger sequencing combined ddPCR methods for mtDNA heteroplasmy quantification in a clinical setting.

PMID:37462790 | DOI:10.1007/s10815-023-02878-w

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A multi-institutional study of short-term mortality in COVID-positive patients undergoing hip fracture surgery: is survival better than expected?

Eur J Orthop Surg Traumatol. 2023 Jul 18. doi: 10.1007/s00590-023-03620-z. Online ahead of print.

ABSTRACT

PURPOSE: Early reports of 30-day mortality in COVID-positive patients with hip fracture were often over 30% and were higher than historical rates of 10% in pre-COVID studies. We conducted a multi-institutional retrospective cohort study to determine whether the incidence of 30-day mortality and complications in COVID-positive patients undergoing hip fracture surgery is as high as initially reported.

METHODS: A retrospective chart review was performed at 11 level I trauma centers from January 1, 2020 to May 1, 2022. Patients 50 years or older undergoing hip fracture surgery with a positive COVID test at the time of surgery were included. The primary outcome measurements were the incidence of 30-day mortality and complications. Post-operative outcomes were reported using proportions with 95% confidence interval (C.I.).

RESULTS: Forty patients with a median age of 71.5 years (interquartile range, 50-87 years) met the criteria. Within 30-days, four patients (10%; 95% C.I. 3-24%) died, four developed pneumonia, three developed thromboembolism, and three remained intubated post-operatively. Increased age was a statistically significant predictor of 30-day mortality (p = 0.01), with all deaths occurring in patients over 80 years.

CONCLUSION: In this multi-institutional analysis of COVID-positive patients undergoing hip fracture surgery, 30-day mortality was 10%. The 95% C.I. did not include 30%, suggesting that survival may be better than initially reported. While COVID-positive patients with hip fractures have high short-term mortality, the clinical situation may not be as dire as initially described, which may reflect initial publication bias, selection bias introduced by testing, or other issues.

LEVELS OF EVIDENCE: Therapeutic Level III.

PMID:37462783 | DOI:10.1007/s00590-023-03620-z

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Evaluating the Patient Boarding during Omicron Surge in Hong Kong: Time Series Analysis

J Med Syst. 2023 Jul 18;47(1):76. doi: 10.1007/s10916-023-01964-x.

ABSTRACT

The fifth wave of COVID-19 outbreaks in Hong Kong (HK) from January to March 2022 has the highest confirmed cases and deaths compared with previous waves. Severe hospital boarding (to inpatient wards) was noted in various Emergency Departments (EDs). Our objective is to identify factors associated with hospital boarding during Omicron surge in HK. We conducted a retrospective cohort study including all ED visits and inpatient (IP) ward admissions from January 1st to March 31st, 2022. Vector Autoregression model evaluated the effects of a single variable on the targeted hospital boarding variables. Admissions from elderly homes with 6 lag days held the highest positive value of statistical significance (t-stat = 2.827, P < .05) caused prolonged admission waiting time, while medical patients with 4 lag days had the highest statistical significance (t-stat = 2.530, P < .05) caused an increased number of boarding patients. Within one week after impulses, medical occupancy’s influence on the waiting time varied from 0.289 on the 1st day to -0.315 on the 7th day. While occupancy of medical wards always positively affected blocked number of patients, and its response was maximized at 0.309 on the 2nd day. Number of confirmed COVID-19 cases was not the sole significant contributor, while occupancy of medical wards was still a critical factor associated with patient boarding. Increasing ward capacity and controlling occupancy were suggested during the outbreak. Moreover, streamlining elderly patients in ED could be an approach to relieve pressure on the healthcare system.

PMID:37462766 | DOI:10.1007/s10916-023-01964-x

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Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor

Zhonghua Zhong Liu Za Zhi. 2023 Jul 23;45(7):613-620. doi: 10.3760/cma.j.cn112152-20211201-00886.

ABSTRACT

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

PMID:37462018 | DOI:10.3760/cma.j.cn112152-20211201-00886

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P077 Incidence of Colonic Strictures – A Systematic Review and Meta-analysis

Am J Gastroenterol. 2021 Dec 1;116(Suppl 1):S20. doi: 10.14309/01.ajg.0000798908.85532.2d.

ABSTRACT

BACKGROUND: Intestinal strictures are a complication of the inflammatory bowel diseases (IBD, including ulcerative colitis (UC) and Crohn’s disease (CD)) that can lead to bowel obstruction and therapy failure. Intestinal strictures occurring after long-standing tissue damage and repair are more frequently reported in CD, but colonic strictures can occur in UC. However, there is a paucity of literature that comprehensively summarizes the available information regarding the incidence and etiology of colonic strictures in UC. The aim of this study was to perform a systematic review and meta-analysis of published reports on the incidence of colonic strictures in UC patients.

METHODS: Four independent reviewers performed a comprehensive review of all original articles describing the incidence of colonic strictures in UC published from inception to June 2021. Primary outcomes were (1) overall incidence of colonic strictures; (2) 10-year incidence of colonic strictures; and (3) incidence of colonic strictures containing high-grade dysplasia (HGD) or colorectal cancer (CRC). Subgroup analysis was performed to compare the outcomes between the pre-biologic era and post-biologic era. The meta-analysis was performed and the statistics were 2-tailed. Finally, probability of publication bias was assessed using funnel plots and with Egger’s test.

RESULTS: Eleven studies reporting on a total of — patients with colonic strictures were included in the analysis after comprehensive search. This yielded a pooled colonic stricture incidence rate of 5.4% (95% confidence interval (CI) 3.7-7.8). The incidence rate of colonic strictures was lower in the post-biologic era compared to the pre-biologic era but the difference was not statistically significant (2.6% vs 6%; p = 0.14). The pooled 10-year colonic stricture rate was 3.2% (95% CI 1.5-6.8). The pooled 10-year incidence rate of colonic strictures was lower in the post-biologic era compared to the pre-biologic era but the difference was not statistically significant (1% vs 1.8%; p = 0.1). The pooled incidence of strictures with associated high-grade dysplasia (HGD) or colorectal cancer (CRC) was 21.9% (95% CI 12.2-36.5). The incidence rate of HGD or CRC in colonic strictures was higher in the post-biologic era compared to the pre-biologic era but the difference was not statistically significant (23.6% vs 20.4%; p = 0.79).

CONCLUSION: This systematic review and meta-analysis on the incidence of colonic strictures in UC showed that the overall pooled incidence and 10-year incidence of colonic strictures in UC are low. There was a trend towards lower incidences of UC strictures in the post-biologic era, although the differences did not reach statistical significance. While the overall incidence of colonic strictures, in UC is low, a high proportion of colonic strictures are associated with HGD or CRC, even in the biologic era. Therefore, this study provides further support for importance of stricture biopsy and surgical evaluation for colectomy in the UC patient with colonic stricture.

PMID:37461993 | DOI:10.14309/01.ajg.0000798908.85532.2d

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P075 Urgency and its Association with Quality of Life and Clinical Outcomes in Ulcerative Colitis Patients

Am J Gastroenterol. 2021 Dec 1;116(Suppl 1):S19-S20. doi: 10.14309/01.ajg.0000805324.84795.58.

ABSTRACT

BACKGROUND: Urgency, the immediate need to defecate, is common in ulcerative colitis (UC). The frequently used patient reported outcome (PRO)-2 for UC includes only rectal bleeding and stool frequency. We sought to investigate the association of urgency in UC patients with 1) quality of life (QoL) domains and 2) future UC hospitalizations, steroid prescriptions, and colectomy.

METHODS: We conducted a cross-sectional and then a subsequent longitudinal study within IBD Partners, a patient-powered research network. We described associations of levels of urgency in UC patients with PROMIS QoL domains (depression, anxiety, social satisfaction, fatigue, sleep, and pain). Next, a longitudinal cohort determined associations between baseline urgency and subsequent clinical outcomes including UC hospitalization, steroid prescription, or colectomy within 12 months. We used bivariate statistics and logistic regression models to describe independent associations.

RESULTS: A total of 632 UC patients were included in the cross-sectional study. After adjusting for clinical variables, rectal bleeding, and stool frequency, “hurry”, “immediately” and “incontinence” increased the odds of social impairment by 2.05 [1.24-3.4] (p = 0.005), 2.76 [1.1-6.74] (p = 0.028), and 7.7 [1.66-38.3] (p = 0.009) respectively compared to “no hurry”. Urgency also significantly increased the odds of depression, anxiety, and fatigue. In the multivariate pooled logistic regression of the longitudinal cohort, Urgency was associated with a significant stepwise increase in risk of hospitalizations, steroids, and colectomy. “Hurry”, “immediately” and “incontinence” increased the odds of colectomy within 12 months by 1.41 [1.15-1.72] (p < 0001), and 3.29 [2.13-5.09] (p < 0001).

CONCLUSION: We demonstrate that urgency is a PRO independently associated with compromised QoL in patients with UC. Urgency is associated with future risk of hospitalizations, steroid prescription, and colectomy. Our findings support the consideration of urgency as a UC-specific PRO and its use as an outcome in clinical trials to capture QoL and risk of clinical decompensation.

PMID:37461991 | DOI:10.14309/01.ajg.0000805324.84795.58

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P070 Next Generation Wearable Technology for IBD Patients: A Feasibility Study

Am J Gastroenterol. 2021 Dec 1;116(Suppl 1):S18. doi: 10.14309/01.ajg.0000798880.74975.18.

ABSTRACT

BACKGROUND: Inflammatory Bowel Disease (IBD) prevalence is rising. Quality of life (QOL) in chronic illness is affected by various physical and psychosocial factors. Recent studies in other chronic illnesses have used remote physiologic monitoring (RPM) to help predict changes in disease activity and provide opportunities for patient self-management. It has been proposed that bowel inflammation can lead to suboptimal sleep, circadian rhythm disruption and even additional immune system activation. Heart rate variability (HRV) is a validated metric that has been used to predict outcomes and help manage other disease states. To date, there is limited data on the benefit of RPM in IBD care. We wish to explore the potential benefit of the Whoop Strap (new wearable technology device) as a method of RPM for IBD patients.

METHODS: We recruited patients with Ulcerative Colitis from our tertiary care IBD center 18 years and older willing to wear the Whoop Strap 3.0 for 12 months with support from the Penn State Hershey Medical Center, 2020 Department of Medicine House Staff Grant; Clinical Trial Identifier is NCT04333810. During this time, participants were encouraged to use the Whoop mobile application to record symptoms. Physiologic metrics of interest included sleep, resting heart rate (RHR), and HRV; each were correlated to IBD related symptoms. Additionally, we performed monthly “check-ins” to collect disease activity (SCCAI), mood (HADS) and stress (PSS4) questionnaire data. Descriptive statistics were utilized along with correlation coefficient testing to explore potential relationships between Whoop metrics, disease activity scores and patient reported outcomes.

RESULTS: Enrollment is ongoing with 7 participants, one of which was lost to follow up. Of note, 2 patients proactively reached out to communicate concern for an underlying disease flare as they noticed significant change in their Whoop metrics in conjunction with worrying symptoms. Patient 1 subsequently had serologic testing after having increased HRV and elevated RHR several days prior to symptoms; results were consistent with active inflammation exhibiting a rise in C-reactive protein from 0.25 mg/dL in 2020 to 2.82 mg/dL. Fecal calprotectin was also elevated at 566 ug/g. Colonoscopy is scheduled for the near future. Patient 2 also had noticeable HRV and RHR changes alongside significant sleep disturbances, which has prompted additional testing.

CONCLUSION: Remote physiologic monitoring is a feasible way to give patients ownership of their medical care and involve them in the diagnostic and treatment process of their underlying IBD. As exhibited with our preliminary results, the Whoop device appears easy to use and may empower patients to reach out to providers even before symptoms occur, leading to an expedited evaluation for increased disease activity. Our feasibility study will hopefully lead to larger prospective efforts utilizing wearable technology devices such as the Whoop in IBD patients.

PMID:37461987 | DOI:10.14309/01.ajg.0000798880.74975.18

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P066 Real-World Experience of Ustekinumab in Crohn’s Disease Patients With Prior Anti-TNF Therapy at a Tertiary Care Hospital

Am J Gastroenterol. 2021 Dec 1;116(Suppl 1):S17. doi: 10.14309/01.ajg.0000798864.82003.45.

ABSTRACT

BACKGROUND: Ustekinumab (UST) is a monoclonal antibody against the p40 subunit of IL-12/23. It is approved for the treatment of moderate to severe Crohn’s disease (CD) and Ulcerative Colitis. We performed a retrospective study to demonstrate the efficacy and outcomes of UST in CD patients who received prior anti-TNF therapies.

METHODS: We collected a list of all patients who received UST until May 2021. In addition, the list was screened for patients who were on anti-TNFs for treatment of CD in the past. Data was collected for patient demographics, disease characteristics, comorbidities, disease phenotype, age of initiation of UST, prior biologic therapy, time since last biologic therapy, concomitant use of steroids or immunomodulator, inflammatory markers, induction of remission, deep remission. Chi-square tests were used for statistical analysis.

RESULTS: We identified 34 patients (59% females) with CD on UST who failed at least one anti-TNFs before induction with UST. Clinical remission was documented in 70.5% of patients. 29 percent of patients who achieved clinical remission were on concomitant steroids or immunomodulators at the time of induction of remission along with UST. Fifty percent of patients had a fistulizing disease, of which 70% achieved clinical remission with UST. C-reactive protein (CRP) was reported in 70 percent of patients. Mean CRP prior to initiation of UST was 2.4. CRP trended down to 1.98 (p = 0.079, 95% CI: -0.064-1.08). Eighteen percent of patients had fecal calprotectin reported. Mean fecal calprotectin before initiation of UST was 386, and it trended down 175 while on UST (p = 0.148, 95% CI: -106.25-528.46).

CONCLUSION: Our study demonstrates that remission rates in CD patients who have failed prior anti-TNF therapy are high, including for patients with perianal disease. In patients with fistulizing CD, we suggest using UST for higher rates of remission after induction. We also found that for fecal calprotectin, although an excellent surrogate of colon inflammation, compliance amongst patients remains low.

PMID:37461983 | DOI:10.14309/01.ajg.0000798864.82003.45