Category: Nevin Manimala

Mol Imaging Radionucl Ther. 2023 Jun 20;32(2):117-122. doi: 10.4274/mirt.galenos.2021.65902.

ABSTRACT

OBJECTIVES: To investigate the added diagnostic value of delayed imaging at 3 and 4 h compared to 2 h imaging as well as scanning up to 4 h compared to 3, and by this means, diagnosis reclassification or changes in diagnosis across various time points.

METHODS: Seventeen patients clinically suspected of gastroparesis, 8 (47.1%) men and 9 (52.9%) women, according to the standard procedural guidelines, underwent gastric emptying scintigraphy after ingesting a standard meal. One-minute static images in anterior and posterior projections were acquired immediately after ingestion and then at 1-, 2-, 3- , and 4 h time points. For image analysis, a manual region-of-interest was drawn, and then, count of stomach in each projection was used to calculate geometric mean for each time point. Decay correction was applied. At 2-, 3- and 4 h time points, percentage of retained activity was compared to standard values; therefore, each patient was labeled as normal or delayed.

RESULTS: Pairwise correlation between time points was statistically significant. Value of hour 3 shows an extremely strong correlation with the value of hour 4 (r=0.951, p<0.001). In hour 2, of 17 participants, 11 (64.7%) were diagnosed as normal and 6 (35.3%) as delayed. In hour 3, the diagnosis made as delayed rose to 9 (52.9%), whereas normal was 8 (47.1%). Finally, in hour 4, results were 10 (58.8%) as delayed and 7 (41.2%) as normal. All subjects who were labeled as delayed in hour 3 remained with the same diagnosis and 1 out of 8 subjects categorized as normal in hour 3 changed to delayed. For testing agreement, coefficient of kappa was computed between each pair. Agreement between diagnosis in hour 2 with hours 3 or 4 was not strong (kappa <0.6 for both pairs). However, a strong agreement was found between diagnosis in hours 3 and 4 (kappa: 0.881).

CONCLUSION: Because of excellent correlation between values of hours 3 and 4 and strong agreement between the diagnosis in those time points, extending acquisition from 3 to 4 h adds little to the final dai gnosis and may not be noticeably meaningful, especially in the clinical setting.

PMID:37337772 | DOI:10.4274/mirt.galenos.2021.65902

Mol Imaging Radionucl Ther. 2023 Jun 20;32(2):112-116. doi: 10.4274/mirt.galenos.2022.05826.

ABSTRACT

OBJECTIVES: The aim of this study was to compare the treatment responses after ablation with 30-50 mCi radioactive iodine (RAI) and 100 mCi RAI in patients with differentiated thyroid cancer (DTC) who were in the low-risk group according to 2015 American Thyroid Associations Classification (ATA 2015) criteria.

METHODS: Between February 2016 and August 2018, 100 patients who received RAI treatment in our clinic after total thyroidectomy and who were in the low-risk group DTC were included in this retrospective study. These patients were divided into 2 groups: low-activity (30-50 mCi) (group 1) and high-activity (100 mCi) (group 2). While 54 patients were treated with low activity, 46 patients received high activity RAI. The 2 groups were compared according to the 1^st– and 3^rd-year treatment response status.

RESULTS: According to the first-year follow-up, 15 patients were accepted as indeterminate response and 85 patients as excellent response. Three (5.5%) of the patients who were accepted as indeterminate response were in group 1 and 12 (26%) were in group 2. According to the third year follow-up, 1 patient in group 1 and 3 patients in group 2 were accepted as indeterminate response. No biochemical incomplete response or recurrent disease was detected. In the chi-square analysis performed to investigate the relationship between the first-year treatment response and RAI activities, a significant relationship was found (p=0.004). In the Mann-Whitney U test performed to investigate the parameters that may be effective in the treatment response, only the preablative serum thyroglobulin value was shown to have a significant difference between the two groups (p=0.01). In the long-term follow-up of the patients, based on the third year treatment response data, chi-square analysis was performed to evaluate the two groups in terms of treatment responses, and no statistically significant relationship was found (p=0.73).

CONCLUSION: Ablation with 30-50 mCi can be safely applied in DTC patients who are in the ATA 2015 low-risk group and are planned for RAI ablation treatment.

PMID:37337764 | DOI:10.4274/mirt.galenos.2022.05826

Brief Bioinform. 2023 Jun 19:bbad230. doi: 10.1093/bib/bbad230. Online ahead of print.

ABSTRACT

The T-cell receptor (TCR) repertoire is highly diverse among the population and plays an essential role in initiating multiple immune processes. TCR sequencing (TCR-seq) has been developed to profile the T cell repertoire. Similar to other high-throughput experiments, contamination can happen during several steps of TCR-seq, including sample collection, preparation and sequencing. Such contamination creates artifacts in the data, leading to inaccurate or even biased results. Most existing methods assume ‘clean’ TCR-seq data as the starting point with no ability to handle data contamination. Here, we develop a novel statistical model to systematically detect and remove contamination in TCR-seq data. We summarize the observed contamination into two sources, pairwise and cross-cohort. For both sources, we provide visualizations and summary statistics to help users assess the severity of the contamination. Incorporating prior information from 14 existing TCR-seq datasets with minimum contamination, we develop a straightforward Bayesian model to statistically identify contaminated samples. We further provide strategies for removing the impacted sequences to allow for downstream analysis, thus avoiding any need to repeat experiments. Our proposed model shows robustness in contamination detection compared with a few off-the-shelf detection methods in simulation studies. We illustrate the use of our proposed method on two TCR-seq datasets generated locally.

PMID:37337757 | DOI:10.1093/bib/bbad230

Diabetes Obes Metab. 2023 Jun 20. doi: 10.1111/dom.15164. Online ahead of print.

ABSTRACT

AIMS: To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with glimepiride in Korean patients with type 2 diabetes.

MATERIALS AND METHODS: This was a 52-week, multicentre, randomized, parallel-group, open-label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1-2 mg/day for 12 months as an add-on to metformin. Baseline and end of study body composition evaluations included dual-energy X-ray absorptiometry and abdominal computed tomography scans.

RESULTS: Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: -2.59 kg BF mass, -1.94% BF%, -17.55 cm² VAT area, -18.39 cm² SAT area, -0.46% glycated haemoglobin, -18.25 mg/dl fasting blood glucose, -3.7 kg weight, -2.21 cm waist circumference, -1.37 kg/m² body mass index, -6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group.

CONCLUSION: Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well-tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add-on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes.

PMID:37337747 | DOI:10.1111/dom.15164

Minerva Endocrinol (Torino). 2023 Jun 20. doi: 10.23736/S2724-6507.23.03985-4. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study is to investigate the use of once-weekly semaglutide in a real population of patients with type 2 diabetes mellitus (T2DM) over 70 years in two Spanish hospitals.

METHODS: An observational, retrospective, and multicenter clinical study was designed. It included 60 patients with T2DM, with a mean age of 76.5 years, 63.3% women, and a mean of 15.5 years of evolution of T2DM, all managed in the outpatient clinical setting. The primary endpoint was the change in HbA<inf>1c</inf> from baseline to the end of the study. The secondary endpoints included changes in body weight and the proportion of patients achieving HbA<inf>1c</inf> <7.0% and body weight loss >5%.

RESULTS: After 12 months of follow-up, the reductions in HbA<inf>1c</inf> were -0.61±0.9% (P<0.0001) in the total cohort. Body weight reductions were -8.2±5.3 kg (P<0.0001). Overall, 67% reached the objective of an HbA<inf>1c</inf> level of <7%, and 73% achieved a weight loss of ≥5%.

CONCLUSIONS: In routine clinical practice in Spain, the use of semaglutide once a week was associated with statistically significant and clinically relevant improvements in HbA<inf>1c</inf> and body weight in adults aged over 70 years with T2DM, without notable adverse effects, which supports real-world use.

PMID:37337740 | DOI:10.23736/S2724-6507.23.03985-4

J Intensive Care Med. 2023 Jun 20:8850666231182563. doi: 10.1177/08850666231182563. Online ahead of print.

ABSTRACT

PURPOSE: Significant increases in the volume of preprint articles due to the COVID-19 pandemic, we examined the reliability of preprint articles compared to their peer-reviewed publications.

MATERIALS AND METHODS: Preprint articles evaluating experimental studies of select treatment options (anticoagulation, dexamethasone, hydroxychloroquine, remdesivir, and tocilizumab) for COVID-19 in the critically ill, available in a peer-reviewed publication were screened for inclusion within Altmetric (n = 2040). A total of 40 articles met inclusion criteria, with 21 being randomly selected for evaluation. The primary outcome of this evaluation was a change in a study’s reported primary outcome or statistical significance between preprint and peer-reviewed articles. Secondary outcomes included changes in primary/secondary outcome effect size and change in study conclusion.

RESULTS: One article (4.8%, 95% CI 0.12%-23.8%) had a change in the primary outcome. Seven articles (33.3%, 95% CI 14.6%-57.0%) had a change in the primary outcome’s effect measure. Five studies (23.8%, 95% CI 8.2%-47.2%) had changes in statistical significance of at least one secondary outcome. Four studies (19.0%, 95% CI 5.4%-41.9%) had a change in study conclusion.

CONCLUSIONS: In preprint articles of COVID-19 treatments, the provided primary outcome is generally reliable, while interpretation of secondary outcomes should be made with caution, while awaiting completion of the peer-review process.

PMID:37337731 | DOI:10.1177/08850666231182563

Arthritis Rheumatol. 2023 Jun 20. doi: 10.1002/art.42546. Online ahead of print.

ABSTRACT

Retraction: Pavelka, K., Trč, T., Karpaš, K., Vítek, P., Sedláčková, M., Vlasáková, V., Böhmová, J. and Rovenský, J. (2007), The efficacy and safety of diacerein in the treatment of painful osteoarthritis of the knee: A randomized, multicenter, double-blind, placebo-controlled study with primary end points at two months after the end of a three-month treatment period. Arthritis & Rheumatism, 56: 4055-4064. https://doi.org/10.1002/art.23056. The above article, published online on November 29, 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal’s Editor-in-Chief, Dr. Daniel H. Solomon, the American College of Rheumatology, and Wiley Periodicals LLC. The retraction has been agreed following a post-hoc analysis by the research’s funder, TRB Chemedica International SA, that identified a discrepancy between the preliminary results of the post-hoc analysis and the results of the published article. The statistical analysis performed using the original database is deemed no longer reliable and the conclusions of the original study regarding the efficacy of diacerein versus placebo are not supported by robust data. As a result, the editors and funder are issuing this retraction.

PMID:37337725 | DOI:10.1002/art.42546

J Vet Diagn Invest. 2023 Jun 20:10406387231182102. doi: 10.1177/10406387231182102. Online ahead of print.

ABSTRACT

Based on publications reporting improvements in real-time PCR (rtPCR) performance, we compared protocols based on heat treatment or dilution followed by direct rtPCR to standard extraction and amplification methods for the detection of porcine reproductive and respiratory syndrome virus (PRRSV), influenza A virus (IAV), porcine epidemic diarrhea virus (PEDV), or Mycoplasma hyopneumoniae (MHP) in swine oral fluids (OFs). In part A, we subjected aliquots of positive OF samples to 1 of 4 protocols: protocol 1: heat (95°C × 30 min) followed by direct rtPCR; protocol 2: heat and cool (25°C × 20 min) followed by direct rtPCR; protocol 3: heat, cool, extraction, and rtPCR; protocol 4 (control): extraction and then rtPCR. In part B, positive OF samples were split into 3, diluted (D1 = 1:2 with Tris-borate-EDTA (TBE); D2 = 1:2 with negative OF; D3 = not diluted), and then tested by rtPCR using the best-performing protocol from part A (protocol 4). In part A, with occasional exceptions, heat treatment resulted in marked reduction in the detection of target and internal sample control (ISC) nucleic acids. In part B, sample dilution with TBE or OF produced no improvement in the detection of targets and ISCs. Thus, standard extraction and amplification methods provided superior detection of PRRSV, IAV, PEDV, and MHP nucleic acids in OFs.

PMID:37337714 | DOI:10.1177/10406387231182102

Mol Imaging Radionucl Ther. 2023 Jun 20;32(2):94-102. doi: 10.4274/mirt.galenos.2022.97658.

ABSTRACT

OBJECTIVES: This prospective study was planned to compare the predictive value of dynamic ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in locally advanced breast cancer patients (LABC) receiving neoadjuvant chemotherapy (NAC).

METHODS: Twenty seven patients with LABC [median age: 47, (26-66)] underwent a dynamic ¹⁸F-FDG PET study at baseline, and after 2-3 cycles of (NAC) were included (interim). Maximum standardized uptake value (SUV_max) values and SUV ratios for the 2^nd, 5^th, 10^th, and 30^th minutes and dynamic curve slope (SL) values and SL ratios were measured using ¹⁸F-FDG dynamic data. In addition, the values of SUV_mean (2minSUVmean), SULpeak (2minSULpeak), metabolic volume (2minVol), and total lesion glycolysis (2minTLG) were measured for the first 2 min. Percent changes between baseline and interim studies were calculated and compared with the pathological results as the pathological complete response (PCR) or the pathological non-complete response (non-PCR). Receiver operating characteristic curves were obtained to calculate the area under the curve to predict PCR. Optimal threshold values were calculated to discriminate between PCR and non-PCR groups.

RESULTS: Baseline study SUV 30 (p=0.044), SUV 30/2 (p=0.041), SUV 30/5 (p=0.049), SUV 30/10 (p=0.021), SL 30/2 (p=0.029) and SL 30/5 (p=0.027) values were statistically significant different between PCR and non-PCR groups. The percentage changes of 2minVol between PCR and non-PCR groups were statistically significant. For the threshold value of -67.6% change in 2minVol, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 87.2%, 77.8%, 63.6%, 93.3%, and 80.7%, respectively (area under the curve: 0.826, p=0.009).

CONCLUSION: Semiquantitative parameters for dynamic ¹⁸F-FDG PET can predict PCR. % changes in 2minVol can identify non-responding patients better than other parameters.

PMID:37337702 | DOI:10.4274/mirt.galenos.2022.97658

Eur J Clin Invest. 2023 Jun 19:e14040. doi: 10.1111/eci.14040. Online ahead of print.

ABSTRACT

BACKGROUND: Hypothermia is an effective method of reducing brain injury caused by a variety of neurological insults. It is aimed to elucidate whether a change in the expression of PERK-mediated pathway proteins is an indicator of the neuroprotective effect of mild hypothermia after cerebral ischaemia/reperfusion.

METHODS: One hundred and ninety-two male C57BL/6 mice were randomly divided into three groups: a sham group, a cerebral normothermic ischaemia/reperfusion (I/R) group and a cerebral hypothermic I/R group. A cerebral ischaemia model was established by ligating the bilateral common carotid artery for 15 min. Mice in the hypothermia group stayed in a cage that was set at 33°C, sprayed with a spray of 70% ethanol, and blown with two high-speed fans. The state of neurons was assessed on micropreparations stained with haematoxylin-eosin and TUNEL. The expressions of GRP78, p-perk, p-eif2α, ATF4 and CHOP were measured by western blot analysis 6, 12, 24 and 72 h after reperfusion.

RESULTS: The number of surviving cells was significantly higher in the hypothermia group than in the group without hypothermia (p < .05). The GRP78 expression in the hypothermia group was statistically higher (p < .05) than in the ischaemia/reperfusion group. Optical densities of p-perk, p-eif2α and ATF4 in hippocampus CA1 neurons ischaemia were statistically significantly lower in the hypothermia group than in the ischaemia/reperfusion group (p < .05). The CHOP expression in the hypothermia group was statistically lower (p < .05) than in the ischaemia/reperfusion group.

CONCLUSION: Mild hypothermia for 6 h promoted moderate neuroprotection by mediating the expression of GRP78, p-PERK, p-eIF2α, ATF4 and CHOP.

PMID:37337313 | DOI:10.1111/eci.14040