Tag: nevin manimala

Am J Nephrol. 2022 Apr 22:1-9. doi: 10.1159/000523961. Online ahead of print.

ABSTRACT

BACKGROUND: Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being developed to treat anemia in patients with chronic kidney disease (CKD) without dialysis dependency.

METHODS: In total, 588 patients with a clinical diagnosis of anemia due to CKD without dialysis need and with baseline hemoglobin of 7.0-10.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat 100 mg oral tablets thrice a week for 24 weeks or biosimilar darbepoetin subcutaneous injection 0.75 μg/kg once in 2 weeks for 24 weeks. The primary outcome was the change from baseline in hemoglobin to evaluation period of Weeks 16-24. Key secondary outcomes included the number of patients with hemoglobin response, changes in the hepcidin levels, changes in the vascular endothelial growth factor (VEGF) levels, and changes in the lipid and lipoprotein profiles.

RESULTS: Hemoglobin change from baseline to Weeks 16-24 was 1.95 g/dL in the desidustat group and 1.83 g/dL in the darbepoetin group (difference: 0.11 g/dL; 95% CI: -0.12, 0.34), which met prespecified non-inferiority margin (-0.75 g/dL). The hemoglobin responders were significantly higher (p = 0.0181) in the desidustat group (196 [77.78%]) compared to the darbepoetin group (176 [68.48%]). The difference of change in hepcidin from baseline to Week 12 and Week 24 (p = 0.0032 at Week 12, p = 0.0016 at Week 24) and the difference of change in low-density lipoprotein from baseline to Week 24 (p value = 0.0269) between the two groups was statistically significant. The difference of change from baseline in VEGF to Weeks 12 and 24 between the two groups was not statistically significant.

CONCLUSION: Desidustat is non-inferior to darbepoetin in the treatment of anemia due to non-dialysis dependent CKD and it is well-tolerated.

PMID:35462372 | DOI:10.1159/000523961

J Environ Manage. 2022 Apr 21;314:115102. doi: 10.1016/j.jenvman.2022.115102. Online ahead of print.

ABSTRACT

A systems analysis perspective related to soil science is necessary to achieve many of the sustainability targets articulated by the United Nations Sustainable Development Goals (SDGs). The System of Environmental-Economic Accounting – Ecosystem Accounting (SEEA-EA) framework is the international statistical standard for quantifying both the contributions that ecosystems make to the economy, and the impacts of economic activity on ecosystems. However, due to the difficulty of obtaining empirical data on ecosystem service flows, in many cases such quantification is informed by ecosystem service models. Previous research on the Mitchell catchment, Queensland Australia provided a novel opportunity to quantify the implications of using a model of hillslope erosion and sediment delivery in isolation (as represented in one of the most frequently used ecosystem service models – InVEST), by comparing such estimates against multiple lines of local empirical data, and a more comprehensive representation of locally important erosion and deposition processes through a sediment budget model. Estimates of the magnitude of hillslope erosion modelled using an approach similar to InVEST and the calibrated sediment budget differed by an order of magnitude. If an uncalibrated InVEST-type model was used to inform the relative distribution of erosion magnitude, findings suggest the incorrect erosion process would be identified as the dominant contributor to suspended sediment loads. However, the sediment budget model could only be calibrated using data on sediment sources and sinks that had been collected through sustained research effort in the catchment. A comparable level of research investment may not be available to inform ecosystem service assessments elsewhere. Findings for the Mitchell catchment demonstrate that practitioners should exercise caution when using model-derived estimates of the sediment retention ecosystem service, which have not been calibrated and validated against locally collected empirical data, to inform an ecosystem account and progress towards achieving the SDGs.

PMID:35462256 | DOI:10.1016/j.jenvman.2022.115102

Fetal Diagn Ther. 2022 Apr 22. doi: 10.1159/000521421. Online ahead of print.

ABSTRACT

INTRODUCTION: The methodological quality of fetal brain charts has not been critically appraised yet.

MATERIAL AND METHODS: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to December 31, 2020. The primary outcome was to evaluate the methodology of the studies assessing the growth of fetal brain structures throughout gestation. A list of 28 methodological quality criteria divided into three domains according to “study design”, “statistical and reporting methods”, and “specific relevant neurosonography aspects” was developed in order to assess the methodological appropriateness of the included studies. The overall quality score was defined as the sum of low risk of bias marks, with the range of possible scores being 0-28. This quality assessment was applied to each individual study reporting reference ranges for fetal brain structures.

RESULTS: Sixty studies were included in the systematic review. The overall mean quality score of the studies included in this review was 51.3%. When focusing on each of the assessed domains, the mean quality score was 53.7% for “study design”, 54.2% for “statistical and reporting methods” and 38.6% for “specific relevant neurosonography aspects”. The sample size calculation, the correlation with a postnatal imaging evaluation and the whole fetal brain assessment were the items at the highest risk of bias for each domain assessed, respectively. The subgroup analysis according to different anatomical location showed the lowest quality score for ventricular and periventricular structures and the highest for cortical structures.

CONCLUSIONS: Most previously published studies reporting fetal brain charts suffers from poor methodology and are at high risk of biases, mostly when focusing on neurosonography issues. Further prospective longitudinal studies aiming at constructing specific growth charts for fetal brain structures should follow rigorous methodology to minimize the risk of biases, guarantee higher levels of reproducibility and improve the standard of care.

PMID:35462359 | DOI:10.1159/000521421

Int J Pediatr Otorhinolaryngol. 2022 Apr 14;157:111133. doi: 10.1016/j.ijporl.2022.111133. Online ahead of print.

ABSTRACT

OBJECTIVE: Repair of pediatric mandibular fractures (PMFs) can be challenging due to the lack of permanent dentition for immobilization, and the presence of unerupted teeth and growth plates in the mandible limiting the space for fixation. Interdental splinting (IDS) has been advocated to provide temporary fixation without the need for mandibular plating; however, there is sparse description of the surgical methodology, and data on long term outcomes are even more limited. The aim of this study is to present our technique and outcomes using a novel technique for IDS repair of pediatric mandible fractures.

STUDY DESIGN: Observational retrospective chart review.

SETTING: Tertiary care pediatric hospital.

SUBJECTS AND METHODS: Pediatric patients requiring operative repair for mandibular fracture at our tertiary care institution between 2004 and 2021 were included. Patients over 18 years of age, those who died due to associated injuries, or those who underwent non-IDS repairs were excluded. Subjects with at least 3 months of follow-up were assessed for efficacy of surgical repair and short-term adverse outcomes, and at least 1 year for long-term adverse events. Descriptive statistics were obtained.

RESULTS: Twenty-three children were included in the study with an average age of 7.4 years (range 2-17 years). Fifty-two percent (52.2%) were female. The most common fracture site was the condyle, occurring in 16 children (70%). The indication for operative repair in all cases was malocclusion. The average duration of maxillomandibular fixation (MMF) with the novel IDS was 21 days (range 12-42 days). The average length of follow up was 1.6 years (range 3 months-11 years). All children had restored, functional occlusion at follow up with none requiring further orthodontic or dental intervention. Three children of the total cohort (13.0%) had prolonged hospitalization beyond 48 h for poor oral intake. Five children (21.7%) experienced minor long-term complications including persistent temporomandibular joint pain (n = 1, 4.3%), infection (n = 2, 8.7%), hypertrophic scar (n = 1, 4.3%) and exposure of hardware (n = 1, 4.3%).

CONCLUSION: PMFs resulting in malocclusion are safely and effectively managed with operative repair utilizing a customizable IDS, with few observed short- and long-term complications.

PMID:35462217 | DOI:10.1016/j.ijporl.2022.111133

J Mol Graph Model. 2022 Apr 19;114:108199. doi: 10.1016/j.jmgm.2022.108199. Online ahead of print.

ABSTRACT

In this study, two approaches were applied to enhance the conformational search from molecular dynamics simulations to determine the transition states of a potential energy surface topology. The main focus is on the augmented dynamics using the swarm particle intelligence and Tsallis statistics molecular dynamics simulations of the phase transition from folding to unfolding state of a peptide in an explicit solvent environment. The transition between nodes is modelled as a random walk in a dynamic graph describing a set of basins in a free energy landscape and their pairwise relations. In this study, a dynamic graph neural networks approach is used to model the dynamic information of each free energy state as the graph evolves by observing the sequential information of edges, the time intervals between edges, and information flow. In addition, a multi-digraph approach is suggested to determine the discrete pathways of the conformation transitions between the states in that free energy surface. Besides, the role of water in the thermal and chemical denaturation of the protein is studied. This study supports the idea that the folding process is characterised by a reaction in water resulting in a reduction of the iceberg formation. Whereas unfolding by another reaction in which equilibrium is shifted towards creating iceberg states in water. In this study, the dipole-dipole correlations between the peptide and solvent are described based on an information-theoretic measure, such as local transfer entropy, to explain the role of waters in the folding/unfolding mechanism.

PMID:35462186 | DOI:10.1016/j.jmgm.2022.108199

Zhonghua Wei Chang Wai Ke Za Zhi. 2022 Apr 25;25(4):342-347. doi: 10.3760/cma.j.cn441530-20220217-00051.

ABSTRACT

Objective: To analyze the association of No.11p posterior lymph node metastasis with clinicopathological features and its prognostic significance in gastric cancer. Methods: A single-center retrospective cohort study was conducted. Clinicopathological data of patients with primary gastric cancers undergoing No.11p posterior lymph node dissection from January 2016 to December 2020 were retrieved from the Database of Gastric Cancer, West China Hospital, Sichuan University. Case inclusion criteria: (1) gastric cancer proved by pathology; (2) radical resection with intraoperative No.11p posterior lymph node dissection; (3) operations performed by the same surgical team; (4) no previous history of other malignant tumors and no concurrent malignant tumors. Those with stump gastric cancer, history of gastrectomy, neoadjuvant chemotherapy, incomplete clinicopathological data and lost to follow-up were excluded. During the operation, the upper edge of the pancreas was retracted forward to expose the area between the upper edge of the pancreas and the splenic vessels. The proximal segment of the splenic artery was skeletonized to remove lymphatic tissue anterior and superior to the splenic artery for No.11p lymph node dissection. For patients with lymphadenopathy in the area between the splenic artery and the splenic vein, dissection was performed. The enlarged lymph nodes were labeled with titanium clips and named as No.11p posterior lymph node. Pathological examination was performed separately after the specimen was isolated. Statistical analysis was performed using R software. Results: A total of 127 gastric cancer patients, who underwent No.11p posterior lymph nodes dissection were included in this study, of which 120 patients without No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes negative) and 7 patients with No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes positive). A total of 8 metastatic No.11p posterior lymph nodes were detected in 7 patients, metastasis rate and with a ratio of 5.5% (7/127) and 6.8% (8/127), respectively. In the subgroup analysis of T3-4 stage patients, the metastasis rate and ratio of No.11p posterior lymph nodes were 9.0% (7/78) and 10.7% (8/75), respectively. Compared to negative cases, patients with No.11p posterior lymph nodes metastasis had larger tumor (P=0.002), higher proportion of Borrmann type Ⅲ and Ⅳ tumors (P=0.005), more metastatic lymph nodes (P<0.001), more advanced T stage (P=0.043), N stage (P=0.004) and TNM stage (P=0.015). In survival analysis, patients with No.11p posterior lymph node metastasis had a significantly worse prognosis than those without metastasis after adjusting for TNM stage (hazard ratio=3.009, 95% confidence interval: 1.824-4.964, P<0.001). Conclusions: The No.11p posterior lymph node metastasis in gastric cancer is associated with worse prognosis. For patients of T3-4 stage gastric cancer, No.11p posterior lymph node dissection should be emphasized during radical operation.

PMID:35461203 | DOI:10.3760/cma.j.cn441530-20220217-00051

Zhonghua Wei Chang Wai Ke Za Zhi. 2022 Apr 25;25(4):336-341. doi: 10.3760/cma.j.cn441530-20210520-00214.

ABSTRACT

Objective: To investigate the safety and efficacy of pelvic peritoneal reconstruction and its effect on anal function in laparoscopy-assisted anterior resection of low and middle rectal cancer. Methods: A prospective cohort study was conducted. Consecutive patients with low and middle rectal cancer who underwent laparoscopy-assisted transabdominal anterior resection at Naval Military Medical University Changhai Hospital from February 2020 to February 2021 were enrolled. Inclusion criteria: (1) the distance from tumor to the anal verge ≤10 cm; (2) laparoscopy-assisted transabdominal anterior resection of rectal cancer; (3) complete clinical data; (4) rectal adenocarcinoma diagnosed by postoperative pathology. Exclusion criteria: (1) emergency surgery; (2) patients with a history of anal dysfunction or anal surgery; (3) preoperative diagnosis of distant (liver, lung) metastasis; (4) intestinal obstruction; (5) conversion to open surgery for various reasons. The pelvic floor was reconstructed using SXMD1B405 (Stratafix helical PGA-PCL, Ethicon). The first needle was sutured from the left anterior wall of the neorectum to the right. Insertion of the needle was continued to suture the root of the sigmoid mesentery while the Hemo-lok was used to fix the suture. The second needle was started from the beginning of the first needle, after 3-4 needles, a drainage tube was inserted through the left lower abdominal trocar to the presacral space. Then, the left peritoneal incision of the descending colon was sutured, after which Hemo-lok fixation was performed. The operative time, perioperative complications, postoperative Wexner anal function score and low anterior resection syndrome (LARS) score were compared between the study group and the control group. Three to six months after the operation, pelvic MRI was performed to observe and compare the pelvic floor anatomical structure of the two groups. Results: A total of 230 patients were enrolled, including 58 who underwent pelvic floor peritoneum reconstruction as the study group and 172 who did not undergo pelvic floor peritoneum reconstruction as the control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time of the study group was longer than that of control group [(177.5±33.0) minutes vs. (148.7±45.5) minutes, P<0.001]. There was no significant difference in the incidence of perioperative complications (including anastomotic leakage, anastomotic bleeding, postoperative pneumonia, urinary tract infection, deep vein thrombosis, and intestinal obstruction) between the two groups (all P>0.05). Eight cases had anastomotic leakage, of whom 2 cases (3.4%) in the study group were discharged after conservative treatment, 5 cases (2.9%) of other 6 cases (3.5%) in the control group were discharged after the secondary surgical treatment. The Wexner score and LARS score were 3.1±2.8 and 23.0 (16.0-28.0) in the study group, which were lower than those in the control group [4.7±3.4 and 27.0 (18.0-32.0)], and the differences were statistically significant (t=-3.018, P=0.003 and Z=-2.257, P=0.024). Severe LARS was 16.5% (7/45) in study group and 35.5% (50/141) in control group, and the difference was no significant differences (Z=4.373, P=0.373). Pelvic MRI examination 3 to 6 months after surgery showed that the incidence of intestinal accumulation in the pelvic floor was 9.1% (3/33) in study group and 46.4% (64/138) in control group (χ(2)=15.537, P<0.001). Conclusion: Pelvic peritoneal reconstruction using stratafix in laparoscopic anterior resection of middle and low rectal cancer is safe and feasible, which may reduce the probability of the secondary operation in patients with anastomotic leakage and significantly improve postoperative anal function.

PMID:35461202 | DOI:10.3760/cma.j.cn441530-20210520-00214

Arch Gerontol Geriatr. 2022 Apr 15;101:104705. doi: 10.1016/j.archger.2022.104705. Online ahead of print.

ABSTRACT

BACKGROUND: Frailty is a syndrome commonly associated with old age. Social relationships are an essential determinant of frailty progression, and frailty can negatively affect social relationships.

OBJECTIVES: To identify social relationship types among older adults in Europe; to evaluate whether social relationship types differ across European regions; and to assess the association between frailty status and social relationship type.

METHODS: We used data from 56,226 individuals from 17 European countries who participated in Wave 6 of the Survey of Health, Ageing and Retirement in Europe. We constructed social relationship types from social relationship variables (contacts frequency, perceived emotional support, participation in social activities, providing and receiving instrumental support) using latent class analysis (LCA). Associations between social relationship types and frailty were examined using multinomial regression analyses integrated with LCA.

RESULTS: We identified four social relationship types: ‘poor’; ‘frequent and emotionally close’; ‘frequent, emotionally close, and supportive’; and ‘frequent, emotionally close, and active’. Type 3 is also characterised by participation in sport/social clubs (in the northern region) or receiving support (in the eastern region). Participation in volunteering/charity activities (in the central and northern regions) and instrumental support provision (in the northern region) are Type 4’s characteristics as well. In all regions, being frail was associated with less active social relationships (Types 1, 2, and 3) relative to the more ‘active’ type (Type 4).

CONCLUSION: Frailty status was associated with social relationship types. The identified types may help tailor intervention programmes for older adults to prevent worsening frailty.

PMID:35461166 | DOI:10.1016/j.archger.2022.104705

J Sport Rehabil. 2022 Apr 23:1-9. doi: 10.1123/jsr.2021-0386. Online ahead of print.

ABSTRACT

CONTEXT: Weight-bearing test (WBT) is a noninvasive quantitative test which has been used recently to determine loading capability of the individuals. The aim of this study was to strengthen the evidence for using the WBT test for measuring weight-bearing capacity of the upper-extremity with the specific objective of examining the internal and external responsiveness and concurrent validity of the test in patients with triangular fibrocartilage complex injury.

DESIGN: Single-group repeated measures.

METHODS: Internal responsiveness was assessed using effect size statistics. The correlation coefficient was used to examine external responsiveness by testing 5 hypotheses regarding predefined correlations between the changes in the measurements. Concurrent validity was evaluated by analyzing correlations between the WBT and other measurements. Thirty-one patients with triangular fibrocartilage complex injury were included for the analysis of the concurrent validity. Eighteen patients who completed all measurements at baseline and at 3-month follow-up enrolled for the responsiveness analysis. Measurements included the WBT, pain intensity, grip strength, and upper extremity functional level.

RESULTS: The WBT test was able to detect statistically significant changes in weight-bearing capacity between baseline and follow-up (P = .0001). The effect size of the WBT was large. Three out of 5 hypotheses (60%) were confirmed, a good correlation was found between changes scores of the WBT and grip strength (r = .478; P < .05). There were significant correlations between the WBT and other measurements (r value range from -.401 to .742; P < .05). A higher correlation was found between the WBT and grip strength (r = .742; P = .0001).

CONCLUSIONS: The responsiveness and concurrent validity of the WBT test confirmed that it is able to measure change in weight-bearing capacity in patients with triangular fibrocartilage complex injury.

PMID:35461186 | DOI:10.1123/jsr.2021-0386

Int Immunopharmacol. 2022 Apr 20;109:108780. doi: 10.1016/j.intimp.2022.108780. Online ahead of print.

ABSTRACT

OBJECTIVE: Tofacitinib is an oral Janus kinase (JAK) inhibitor that has been marketed and approved in the USA for the clinical treatment of rheumatoid arthritis, psoriasis and other inflammatory and autoimmune diseases. A phase I clinical trial was conducted to compare the bioequivalence and safety of tofacitinib (Chia Tai Tianqing Pharmaceutical Group Co., Ltd.) and Xeljanz® (Pfizer Inc.) in healthy Chinese subjects, providing basis for the clinical application of tofacitinib.

METHODS: Healthy Chinese subjects (N = 32) were randomly assigned to two groups at a 1:1 ratio. Subjects orally took 5 mg tofacitinib or Xeljanz® per cycle in random sequence. Blood samples were collected at 15 sampling points per cycle, and plasma drug concentrations of tofacitinib or Xeljanz® were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and statistical analysis for the pharmacokinetic (PK) parameters. Subjects’ physical indicators were monitored during the whole process to evaluate drug safety.

RESULTS: The adjusted geometric mean ratios (GMRs) of the peak concentration (C_max), area under the curve (AUC) from time zero to the last measurable concentration (AUC_0-t) and AUC from time zero to observed infinity (AUC_0-∞) were all within the range of 80-125%. The other PK parameter values were similar. The above values were all meeting the bioequivalence criteria with well safety.

CONCLUSION: The pharmacokinetic parameters and safety profile of tofacitinib were similar to those of Xeljanz® in healthy Chinese subjects. Therefore, tofacitinib can be considered bioequivalent to Xeljanz®, and the findings of this trial will promote the clinical application of tofacitinib.

PMID:35461158 | DOI:10.1016/j.intimp.2022.108780