Categories
Nevin Manimala Statistics

Antibody Response and Safety After mRNA-1273 SARS-CoV-2 Vaccination in Peritoneal Dialysis Patients – the Vienna Cohort

Front Immunol. 2021 Dec 2;12:780594. doi: 10.3389/fimmu.2021.780594. eCollection 2021.

ABSTRACT

BACKGROUND: Dialysis patients are at high risk for a severe clinical course after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Safety and early immune responses after mRNA-based vaccination have been reported mostly in patients on hemodialysis (HD), whereas reports of peritoneal dialysis (PD) patients remain rare.

METHODS: In this retrospective observational study, 39 PD patients had received two doses of the mRNA-1273 Moderna® vaccine. We analyzed SARS-CoV-2 Spike (S) antibody titers 4 weeks after each dose of mRNA-1273 and report local and systemic side effects in PD patients that occurred within one week after each mRNA-1273 dose. Using a quantile regression model we examined factors that might influence SARS-CoV-2 S antibody levels in PD patients.

RESULTS: Four weeks after the first dose of mRNA-1273 vaccine 33 of 39 (84.6%) PD patients seroconverted and presented with 6.62 U/mL (median; IQR 1.57-22.5) anti-SARS-CoV-2 S antibody titers. After the second dose, 38 of 39 (97.4%) PD patients developed anti-SARS-CoV-2 S antibodies and titers increased significantly (median 968 U/mL; IQR 422.5-2500). Pain at the injection site was the most common local adverse event (AE) (71%). Systemic AEs occurring after the first dose were mostly fatigue (33%) and headache (20%). No severe systemic AEs were reported after the first injection. After the second dose the incidence and the severity of the systemic AEs increased. The most common systemic AEs were: fatigue (40.5%), headache (22.5%), joint pain (20%), myalgia (17.5%) and fever (13%). Lower Davies Comorbidity Score (p=0.04) and shorter dialysis vintage (p=0.017) were associated with higher antibody titers after the first dose. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose (p=1.53×10-05).

CONCLUSIONS: Peritoneal dialysis patients in this cohort had a high seroconversion rate of 97.4%, showed high antibody titers after full vaccination and tolerated the anti-SARS-CoV-2 mRNA-1273 vaccine well without serious adverse events.

PMID:34925359 | PMC:PMC8674530 | DOI:10.3389/fimmu.2021.780594

Categories
Nevin Manimala Statistics

Evidence for the Application of Emerging Technologies to Accelerate Crop Improvement – A Collaborative Pipeline to Introgress Herbicide Tolerance Into Chickpea

Front Plant Sci. 2021 Dec 3;12:779122. doi: 10.3389/fpls.2021.779122. eCollection 2021.

ABSTRACT

Accelerating genetic gain in crop improvement is required to ensure improved yield and yield stability under increasingly challenging climatic conditions. This case study demonstrates the effective confluence of innovative breeding technologies within a collaborative breeding framework to develop and rapidly introgress imidazolinone Group 2 herbicide tolerance into an adapted Australian chickpea genetic background. A well-adapted, high-yielding desi cultivar PBA HatTrick was treated with ethyl methanesulfonate to generate mutations in the ACETOHYDROXYACID SYNTHASE 1 (CaAHAS1) gene. After 2 years of field screening with imidazolinone herbicide across >20 ha and controlled environment progeny screening, two selections were identified which exhibited putative herbicide tolerance. Both selections contained the same single amino acid substitution, from alanine to valine at position 205 (A205V) in the AHAS1 protein, and KASP™ markers were developed to discriminate between tolerant and intolerant genotypes. A pipeline combining conventional crossing and F2 production with accelerated single seed descent from F2:4 and marker-assisted selection at F2 rapidly introgressed the herbicide tolerance trait from one of the mutant selections, D15PAHI002, into PBA Seamer, a desi cultivar adapted to Australian cropping areas. Field evaluation of the derivatives of the D15PAHI002 × PBA Seamer cross was analyzed using a factor analytic mixed model statistical approach designed to accommodate low seed numbers resulting from accelerated single seed descent. To further accelerate trait introgression, field evaluation trials were undertaken concurrent with crop safety testing trials. In 2020, 4 years after the initial cross, an advanced line selection CBA2061, bearing acetohydroxyacid synthase (AHAS) inhibitor tolerance and agronomic and disease resistance traits comparable to parent PBA Seamer, was entered into Australian National Variety Trials as a precursor to cultivar registration. The combination of cross-institutional collaboration and the application of novel pre-breeding platforms and statistical technologies facilitated a 3-year saving compared to a traditional breeding approach. This breeding pipeline can be used as a model to accelerate genetic gain in other self-pollinating species, particularly food legumes.

PMID:34925421 | PMC:PMC8678039 | DOI:10.3389/fpls.2021.779122

Categories
Nevin Manimala Statistics

Bone Turnover Markers in Response to Ultrasound-Guided Microwave Ablation for Primary Hyperparathyroidism

Front Endocrinol (Lausanne). 2021 Dec 1;12:782050. doi: 10.3389/fendo.2021.782050. eCollection 2021.

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of primary hyperparathyroidism (PHPT), and to investigate whether MWA can improve the bone turnover and renal function.

METHODS: A total of 20 consecutive PHPT patients with 21 parathyroid lesions treated with MWA in our center from May 2019 to March 2021 were recruited in this study. Serum parathyroid hormone (PTH), calcium and phosphorus levels before MWA and at 20 minutes, 4 hours, 1 day, 3 months, 6 months and 12 months after MWA were measured. Bone turnover biomarkers, renal function and lesion volume with volume reduction rate (VRR) before MWA and at the last follow-up were compared. Any complication related with MWA was evaluated. The technical and clinical success rates of MWA in the treatment of PHPT were calculated. Clinical success was defined as normal serum PTH and calcium without PHPT-associated manifestations at more than 6 months after ablation. Technical success was defined as complete ablation indicated by immediate postoperative contrast-enhanced ultrasound.

RESULTS: The serum PTH, calcium and phosphorus levels at their respective follow-up time points dropped significantly after MWA (P <0.05). The volume of parathyroid lesions at the final examination was significantly reduced, compared with pre-ablation volume (P <0.001), with a median VRR reaching 89%. The technical and clinical success rates were 100% and 63.6%, respectively. Substantial changes of bone turnover biomarkers were observed before and after MWA (P <0.05), but the differences in renal function were not statistically significant. No major complications were reported in all cases. Pre-MWA serum PTH, lesion volume, maximum diameter of lesion and ablation time were significantly different between patients with successful and failed MWA.

CONCLUSIONS: PHPT can be effectively and safely treated by ultrasound-guided MWA, as proven by drop in serum PTH and reduction in the volume of parathyroid adenomas. Besides, MWA can impede bone remodeling to suppress hyperparathyroidism in the condition of PHPT.

PMID:34925241 | PMC:PMC8672162 | DOI:10.3389/fendo.2021.782050

Categories
Nevin Manimala Statistics

Vitamin D Metabolic Pathway Genes Polymorphisms and Their Methylation Levels in Association With Rheumatoid Arthritis

Front Immunol. 2021 Dec 2;12:731565. doi: 10.3389/fimmu.2021.731565. eCollection 2021.

ABSTRACT

Abnormal vitamin D metabolism is involved in the pathogenesis of rheumatoid arthritis (RA). In this study, we evaluated the association of single nucleotide polymorphisms (SNPs) and methylation levels in vitamin D metabolic pathway genes with RA susceptibility. Ten SNPs in vitamin D metabolic pathway genes (CYP2R1, CYP24A1, VDR, CYP27B1) were genotyped in 477 RA patients and 496 controls by improved multiple ligase detection reaction (iMLDR). The methylation levels of the promoter regions of these genes were detected in 122 RA patients and 123 controls using Illumina Hiseq platform. We found that the CYP2R1 rs1993116 GA genotype, CYP27B1 rs4646536 GA genotype, rs4646536 A allele frequencies were significantly increased in RA patients when compared to controls. The decreased risk of rs1993116, rs4646536 was found under the dominant mode in RA patients. However, no significant association was found between CYP2R1 rs7936142, rs12794714, CYP24A1 rs2762934, rs6068816, rs2296239, rs2296241, VDR rs11574129, rs3847987 polymorphism, and RA susceptibility. The VDR, CYP27B1 methylation levels in RA patients were significantly lower than those in controls, while CYP2R1, CYP24A1 methylation levels were not associated with RA. There were no statistical associations between CYP2R1, CYP24A1, VDR, CYP27B1 methylation levels and their respective genotype in RA patients. In addition, plasma 25OHD level in RA patients was significantly lower than that in healthy controls. In summary, our results showed that CYP2R1, CYP27B1 genetic variations were associated with the genetic background of RA, while altered VDR, CYP27B1 methylation levels were related to the risk of RA.

PMID:34925313 | PMC:PMC8677352 | DOI:10.3389/fimmu.2021.731565

Categories
Nevin Manimala Statistics

Effect of peritoneum reconstruction on postoperative complications after laparoscopic low anterior resection for rectal cancer

Zhonghua Wei Chang Wai Ke Za Zhi. 2021 Dec 25;24(12):1079-1085. doi: 10.3760/cma.j.cn441530-20210209-00061.

ABSTRACT

Objective: To determine the effect of peritoneum reconstruction on postoperative complications after laparoscopic low anterior resection (LAR) for rectal cancer. Methods: Retrospective cohort study and propensity score matching were conducted. Case inclusion criteria: (1) pathologically confirmed rectal adenocarcinoma; (2) 18 to 80 years; (3) patients with middle to low rectal cancer undergoing laparoscopic LAR; (4) patients staging cT1-4aN0-2M0 or ycT1-4aN0-2M0 after neoadjuvant therapy; (5) the distance of 4-10 cm from tumor low margin to anal verge. Exclusion criteria: (1) abdominal surgery history (except appendicitis, cholecystitis, ectopic pregnancy); (2) anastomosis above the peritoneal reflection; (3) tumor distant metastasis or clinical staging of T4b during surgery; (4) conversion to open surgery; (5) severe incapacitating disease (American Society of Anesthesiologists classification IV or V, ASA). A total of 666 patients with middle to low rectal cancer undergoing laparoscopic LAR in The First Affiliated Hospital of Army Medical University from January 2017 to June 2020 were enrolled. There were 473 males and 193 females with the median age of 59 (18-80) years. Laparoscopic LAR with peritoneum reconstruction was performed in 188 cases (PR group), and laparoscopic LAR without peritoneum reconstruction was performed in 478 cases (NPR group). After 1:1 propensity score matching according to 1:1 based on age, gender, body mass index, TNM staging, ASA classification, intraoperative blood loss, distance from tumor low margin to anal edge, 153 cases were included in each group. Postoperative complications were classified according to Clavien-Dindo classification. Anastomotic leakage was defined and graded according to the International Study Group of Rectal Cancer (ISGRC) criteria. Results: After propensity score matching, there were no significant differences in baseline demographic characteristics between the 2 groups (all P>0.05), indicating that these two groups were comparable. (1) Operative conditions: All the patients in both groups completed operation successfully. Compared with the NPR group, the PR group had longer operation time [(181.3±60.3) minutes vs. (168.9±51.5) minutes, t=2.185, P=0.029], shorter postoperative median hospital stay [8 (7, 10) days vs. 9 (7, 11) days, Z=-2.282, P=0.022], and the differences were statistically significant (P<0.05). (2) Postoperative complications: The overall morbidity of postoperative complication in PR group and NPR group was 20.3% (31/153) and 24.2% (37/153) respectively, and the incidence of anastomotic leakage was 9.8% (15/153) and 11.1%(17/153) respectively, whose differences were not statistically significant (both P>0.05). Compared with NPR group, PR group had lower morbidity of grade III to IV complications [3.9% (6/153) vs. 11.1% (17/153), χ(2)=5.688, P=0.017] and lower secondary operation rate [1.3% (2/153) vs. 5.9% (9/153), χ(2)=4.621, P=0.032], the differences were statistically significant (both P<0.05). Though PR group had lower incidence of grade C anastomoic leakage [1.3% (2/153) vs. 3.9% (6/153), χ(2)=2.054, P=0.152], but the differences were not statistically significant. (3) Postoperative inflammation: The difference of the procalcitonin level of both PR and NPR groups at postoperative 1-d, 3-d, and 5-d was statistically significant (F=5.222, P=0.010) in time-dependent manner, while the difference was not significant in the interaction effect (P>0.05). No statistically significant differences in the C-reactive protein level between two groups at postoperative 1-d, 3-d, and 5-d were found (all P>0.05). Conclusion: Peritoneum reconstruction in laparoscopic LAR can decrease the morbidity of postoperative complication of grade III to IV and the reoperation rate, and plays an important role in controlling the inflammatory reaction, which has great clinical value.

PMID:34923791 | DOI:10.3760/cma.j.cn441530-20210209-00061

Categories
Nevin Manimala Statistics

Use of computational fluid dynamics (CFD) to model observed nasal nitric oxide levels in human subjects

Int Forum Allergy Rhinol. 2021 Dec 18. doi: 10.1002/alr.22913. Online ahead of print.

ABSTRACT

BACKGROUND: Upper airway nitric oxide (NO) is physiologically important in airway regulation and defense, and nasal NO (nNO) levels typically exceed those in exhaled breath (fractional exhaled NO [FeNO]). Elevated concentrations of NO sampled from the nose, in turn, reflect even higher concentrations in the paranasal sinuses, suggesting a “reservoir” role for the latter. However, the dynamics of NO flux within the sinonasal compartment are poorly understood.

METHODS: Data from 10 human subjects who had previously undergone both real-time nNO sampling and computed tomography (CT) scanning of the sinuses were analyzed using computational fluid dynamics (CFD) methods. Modeled and observed nNO values during the initial 2-s transient (“spike”) during nasal exhalation were then compared.

RESULTS: Examining the initial 2-s transient spike for each subject (as well as the pooled group), there was a statistically significant correlation between modeled and observed nNO levels, with r values ranging from 0.43 to 0.89 (p values ranging from <0.05 to <0.0001). Model performance varied between subjects, with weaker correlations evident in those with high background (FeNO) levels. In addition, the CFD simulation suggests that ethmoid sinuses (>60%) and diffusion process (>54%) contributed most to total nasal NO emissions.

CONCLUSION: Analysis of this dataset confirms that CFD is a valuable modeling tool for nNO dynamics, and highlights the importance of the ethmoid sinuses, as well as the role of diffusion as an initiating step in sinonasal NO flux. Future model iterations may apply more generally if baseline FeNO is taken into account.

PMID:34923761 | DOI:10.1002/alr.22913

Categories
Nevin Manimala Statistics

One-year outcomes of laparoscopic single-anastomosis duodenal-ileal bypass with sleeve gastrectomy versus laparoscopic sleeve gastrectomy for the treatment of obesity and obesity-related metabolic diseases

Zhonghua Wei Chang Wai Ke Za Zhi. 2021 Dec 25;24(12):1058-1064. doi: 10.3760/cma.j.cn441530-20210126-00044.

ABSTRACT

Objective: To compare the efficacy and safety of laparoscopic single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) and laparoscopic sleeve gastrectomy (SG) in the treatment of obesity and obesity-related metabolic diseases. Methods: A retrospective cohort study method was used to analyze the clinical data of 22 patients with obesity who underwent laparoscopic SADI-S in the China-Japan Union Hospital of Jilin university from May 2018 to December 2019 (SADI-S group). Meanwhile, 22 patients with obesity undergoing laparoscopic SG at the same period were selected in this study whose preoperative demographics, including sex, age, body weight, body mass index, metabolic diseases and blood index, were comparable to those of SADI-S group. All the patients were followed up at 3 months, 6 months and 12 months after operation to compare the weight loss [body weight, body mass index, percent of excess weight loss (%EWL) and percent of total weight loss (%TWL), etc.], remission of obesity-related metabolic diseases (hypertension, hyperuricemia, and type 2 diabetes mellitus, etc.) and nutritional deficiency (albumin, retinal-binding-protein, vitamin B12, vitamin D and iron protein, etc.) between the two groups. Results: All the patients successfully underwent laparoscopic bariatric surgery without conversion to laparotomy or death. Compared with SG group, SADI-S group had longer operative time [(204.8±38.3) minutes vs. (109.2±22.4) minutes, t=10.107, P<0.001], higher rate of intraoperative drainage tube [100.0% (22/22) vs. 50.0% (11/22), P<0.001], longer duration of indwelling drainage tube [4 (2-7) days vs. 1 (0-7) days, U=131.000, P=0.008], and the differences were statistically significant (all P<0.05). There was no significant difference between the SG group and the SADI-S group in terms of postoperative hospital stay and complication rate. The weight loss efficacy of SADI-S group and SG group was compared at 3, 6 and 12 months after operation. The results showed that with the increase of follow-up time, the patient’s body weight and body mass index gradually decreased, %EWL and %TWL gradually increased (all P<0.05). There were no statistically significant differences in body weight, body mass index and %EWL between the SADI-S group and the SG group at 3, 6 and 12 months after operation (all P>0.05). There was no statistically significant difference of %TWL between two groups at 3 months after operation (F=0.846, P=0.368), but SADI-S group had higher %TWL at 6 and 12 months after operation and the differences were statistically significant (6-month: 34.0±5.1 vs. 30.2±4.3, F=5.813, P=0.025; 12-month: 42.9±6.8 vs. 34.8±7.6, F=14.262, P=0.001). Except for that the remission rate of total cholesterol of SADI-S group was higher than that of SG group, remission rates of metabolic diseases were not significantly different at different follow-up points (all P>0.05). As for the nutrient deficiency (albumin, retinal-binding-protein, iron protein, vitamin B12, vitamin D and folic acid) and the incidence of gallstones, no significant differences were found between two groups (all P>0.05). Conclusion: Both SADI-S and SG are safe and effective for the treatment of obesity and obesity-related metabolic diseases, but the former is more effective.

PMID:34923788 | DOI:10.3760/cma.j.cn441530-20210126-00044

Categories
Nevin Manimala Statistics

High-frequency ultrasound for differentiation between high-risk basal cell carcinoma and cutaneous squamous cell carcinoma

Skin Res Technol. 2021 Dec 19. doi: 10.1111/srt.13121. Online ahead of print.

ABSTRACT

BACKGROUND: The similar visual appearance of high-risk basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) may cause confusion for diagnosis. High-frequency ultrasound (HFUS) may provide additional intralesional information and thus help to distinguish them.

METHOD: In this retrospective study, we analyzed the clinical characteristics, HFUS grayscale, and color Doppler flow imaging (CDFI) features of pathologically confirmed high-risk BCC and cSCC lesions (n = 65 vs n = 68). Subsequently, discrimination models based on the significant HFUS features were established.

RESULTS: Between high-risk BCC and cSCC lesions, the HFUS grayscale features of the lesion size (10.0 mm vs 17.4 mm), thickness (3.1 mm vs 5.9 mm), internal hyperechoic spots (80.0% vs 23.5%), and posterior acoustic shadowing (16.9% vs 66.2%) were statistically different (all p < 0.001). As for the CDFI features, high-risk BCC lesions mainly appeared as pattern II (47.7%), while cSCC lesions mainly appeared as pattern III (66.2%). Based on the above five features, an optimal discrimination model was established with a sensitivity of 91.2%, a specificity of 87.7%, and an accuracy of 89.5%.

CONCLUSION: HFUS features, including size, thickness, internal hyperechoic spots, posterior acoustic shadowing, and Doppler vascularity pattern, are useful for differential diagnosis between high-risk BCC and cSCC.

PMID:34923684 | DOI:10.1111/srt.13121

Categories
Nevin Manimala Statistics

Genetic models and approaches to study orofacial clefts

Oral Dis. 2021 Dec 18. doi: 10.1111/odi.14109. Online ahead of print.

ABSTRACT

INTRODUCTION: Orofacial clefts (OFCs) are common craniofacial birth defects with heterogeneous phenotype and etiology. Geneticists have applied nearly every available method and technology to further our understanding of the genetic architectures of OFCs.

OBJECTIVE: This review describes the evidence for a genetic etiology in OFCs, statistical genetic approaches employed to identify genetic causes, and how the results have shaped our current understanding of the genetic architectures of syndromic and nonsyndromic OFCs.

CONCLUSION: There has been rapid progress towards elucidating the genetic architectures of OFCs due to the availability of large collections of DNA samples from cases, controls, and families with OFCs and the consistent adoption of new methodologies and novel statistical approaches as they are developed. Genetic studies have identified rare and common variants influencing risk of OFCs in both Mendelian and complex forms of OFCs, blurring the distinctions traditional categories used in genetic studies and clinical medicine.

PMID:34923716 | DOI:10.1111/odi.14109

Categories
Nevin Manimala Statistics

Comparison of heart rates at fixed percentages and the ventilatory thresholds in patients with interstitial lung disease

Scand J Med Sci Sports. 2021 Dec 18. doi: 10.1111/sms.14117. Online ahead of print.

ABSTRACT

Heart rate (HR) responses to maximal exercise are commonly used for the prescription of training intensities in pulmonary rehabilitation. Those intensities are usually based on fixed percentages of peak HR (HRpeak), heart rate reserve (HRR), or peak work load (Wpeak), and rarely on HRs at the individual ventilatory thresholds (VT1 and VT2) derived from cardiopulmonary exercise testing (CPET). For patients suffering from interstitial lung disease (ILD), data on cardiorespiratory responses to CPET are scarce. Thus, the aim of this study was to record cardiorespiratory responses to CPET and to compare fixed HR percentages with HRs at VT1 and VT2 in ILD patients. A total of 120 subjects, 80 ILD patients and 40 healthy controls, underwent a symptom-limited CPET. From the ILD patient, 32 suffered from idiopathic pulmonary fibrosis (IPF), 37 from connective tissue disease (CTD) and 11 from sarcoidosis. HRs at fixed percentages, i.e., at 70%HRpeak, at 70%Wpeak and at 60%HRR were significantly lower in the ILD patients compared to the control group (p-values: 0.001, 0.044, and 0.011). Large percentages of HR values at 70%Wpeak and 60%HRR ranged between the HRs at VT1 and VT2 in ILD subgroups and controls as well. HRs at 70%HRpeak were lower than HRs at VT1 in 66% of the IPF patients, 54% of the CTD patients and 55% of patients with sarcoidosis compared to 18% in the control group. Our findings demonstrate a considerable scattering of fixed HR percentages compared to HRs at the individual VTs derived from CPET in ILD patients. These findings may provide valuable information for the prescription of exercise intensity in pulmonary rehabilitation of ILD patients.

PMID:34923682 | DOI:10.1111/sms.14117