Nevin Manimala

Eur Radiol. 2023 Jul 18. doi: 10.1007/s00330-023-09942-0. Online ahead of print.

ABSTRACT

OBJECTIVES: A published tumour regression grade (TRG) score for squamous anal carcinoma treated with definitive chemoradiotherapy based on T2-weighted MRI yields a high proportion of indeterminate responses (TRG-3). We investigate whether the addition of diffusion-weighted imaging (DWI) improves tumour response assessment in the early post treatment period.

MATERIALS AND METHODS: This retrospective observational study included squamous anal carcinoma patients undergoing MRI before and within 3 months of completing chemoradiotherapy from 2009 to 2020. Four independent radiologists (1-20 years’ experience) scored MRI studies using a 5-point TRG system (1 = complete response; 5 = no response) based on T2-weighted sequences alone, and then after a 12-week washout period, using a 5-point DWI-TRG system based on T2-weighted and DWI. Scoring confidence was recorded on a 5-point scale (1 = low; 5 = high) for each reading and compared using the Wilcoxon test. Indeterminate scores (TRG-3) from each reading session were compared using the McNemar test. Interobserver agreement was assessed using kappa statistics.

RESULTS: Eighty-five patients were included (mean age, 59 years ± 12 [SD]; 55 women). T2-weighted TRG-3 scores from all readers combined halved from 24% (82/340) to 12% (41/340) with DWI (p < 0.001). TRG-3 scores changed most frequently (41%, 34/82) to DWI-TRG-2 (excellent response). Complete tumour response was recorded clinically in 77/85 patients (91%). Scoring confidence increased using DWI (p < 0.001), with scores of 4 or 5 in 84% (287/340). Interobserver agreement remained fair to moderate (kappa range, 0.28-0.58).

CONCLUSION: DWI complements T2-weighted MRI by reducing the number of indeterminate tumour responses (TRG-3). DWI increases radiologist’s scoring confidence.

CLINICAL RELEVANCE STATEMENT: Diffusion-weighted imaging improves T2-weighted tumour response assessment in squamous anal cancer, halving the number of indeterminate responses in the early post treatment period, and increases radiologists’ confidence.

KEY POINTS: Tumour response based on T2-weighted MRI is often indeterminate in squamous anal carcinoma. Diffusion-weighted imaging alongside T2-weighted MRI halved indeterminate tumour regression grade scores assigned by four radiologists from 24 to 12%. Scoring confidence of expert and non-expert radiologists increased with the inclusion of diffusion-weighted imaging.

PMID:37462820 | DOI:10.1007/s00330-023-09942-0

Clin Exp Med. 2023 Jul 18. doi: 10.1007/s10238-023-01132-y. Online ahead of print.

ABSTRACT

To compare the clinical effectiveness and safety of novel biologics for the treatment of lupus nephritis based on a reticulated meta-analysis approach. Registered clinical trials in 4 major databases (PubMed, Embase, Web of Science, The Cochrane Register of Clinical Trials) and ClinicalTrials.gov were systematically searched with a search time frame of build to June 2022. And we screened registered randomized controlled clinical trials of biologics for the treatment of lupus nephritis according to the protocol’s nadir criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 and Review Manager 5.3 software to compare and rank differences in effectiveness and safety between the biologics. A total of 10 registered randomized controlled clinical trials involving 2148 subjects were included in this study. The interventions were ranked from best to worst in terms of the primary outcome indicator of effectiveness, renal complete remission: belimumab > anifrolumab (900 + 300) mg > obinutuzumab > ocrelizumab 400 mg > abatacept 30/10 mg/kg > belimumab + rituximab > abatacept 10/10 mg/kg > abatacept (30/10 + 10/10) mg/kg > placeo > ocrelizumab 1000 mg > rituximab > anifrolumab 300 mg, belimumab was superior to placebo [OR = 1.75, 95% CI (1.13, 2.70)] and anifrolumab 300 mg [OR = 3.27, 95% CI (1.05, 10.14)], anifrolumab (900 + 300) mg was superior to anifrolumab 300 mg [OR = 3.56, 95% CI (1.30, 9.76)], and all were statistically significant. The ranking of each intervention in terms of overall renal remission for secondary outcome indicators from best to worst was: obinutuzumab > belimumab + rituximab > anifrolumab (900 + 300) mg > ocrelizumab 1000 mg > ocrelizumab 400 mg > belimumab > rituximab 1000 mg > abatacept 30/10 mg/kg > abatacept (30/10 + 10/10) mg/kg > placeo > abatacept 10/10 mg/kg > anifrolumab 300 mg, obinutuzumab was superior to placebo [OR = 2.27, 95% CI (1.11, 4.67)] and belimumab was also superior to placebo [OR = 1.56, 95% CI (1.07, 2.27)], and all were statistically significant. In terms of safety, with a focus on serious adverse events and serious infections, the results were: Serious adverse events at 1 year of monitoring occurred better with ocrelizumab 1000 mg than ocrelizumab 400 mg [OR = 0.51, 95% CI (0.29, 0.89)] and were statistically different; serious adverse events at 2 years of monitoring infection adverse events occurred better with obinutuzumab than with abatacept (30/10 + 10/10) mg/kg [OR = 0.24, 95% CI (0.07, 0.81)] and were statistically different. The safety of the new biologics in combination with conventional standard therapies is generally good, but it is belimumab and obinutuzumab that are most effective in achieving complete and overall remission in the kidney. This study protocol has been registered with PROSPERO, with a registration number of CRD42021262498.

PMID:37462818 | DOI:10.1007/s10238-023-01132-y

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

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

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

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

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 1^st to March 31^st, 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 1^st day to -0.315 on the 7^th day. While occupancy of medical wards always positively affected blocked number of patients, and its response was maximized at 0.309 on the 2^nd 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

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

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

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