Nevin Manimala

Transplantation. 2022 Apr 14. doi: 10.1097/TP.0000000000004133. Online ahead of print.

ABSTRACT

BACKGROUND: Donor-specific antibodies (DSA) against HLA are an important biomarker predicting graft injury, rejection (Rej), and failure in various solid-organ transplant recipients. However, the impact of DSA with or without histopathological evidence of rejection among pancreas transplant recipients (PTRs) is unknown.

METHODS: In this study, we included all PTRs at our center between 2005 and 2020, with pancreas allograft biopsy before March 31, 2021, and with DSA checked within 15 d of the biopsy. PTRs were divided into 4 groups based on the biopsy findings on the index biopsy and DSA status as Rej-/DSA-, Rej+/DSA-, Rej-/DSA+, and Rej+/DSA+.

RESULTS: Two hundred two PTRs had a pancreas allograft biopsy during the study period. Thirty-nine were in Rej-/DSA-, 84 Rej+/DSA-, 24 Rej-/DSA+, and 55 Rej+/DSA+. The mean interval from transplant to index biopsy was not statistically different between the 4 groups. The most common type of rejection was T cell-mediated rejection; however, antibody-mediated rejection was more prevalent in the Rej+/DSA+ group. At 5 y postbiopsy, the rate of death-censored graft failure (DCGF) for Rej-/DSA- was 18%, 24% in Rej+/DSA-; 17% in Rej-/DSA+ and 36% in Rej+/DSA+ (P = 0.14). In univariate analysis, mixed rejection (hazard ratio [HR], 3.0; 95% confidence intervals [CI], 1.22-7.39; P = 0.02) along with solitary pancreas transplantation and Rej+/DSA+ were associated with DCGF. In multivariate analysis, compared with Rej-/DSA-, Rej+/DSA+ was significantly associated with DCGF (HR, 2.32; 95% CI, 1.03-5.20; P = 0.04); however, Rej+/DSA- was not (HR, 1.06; 95% CI, 0.32-3.56; P = 0.92).

CONCLUSIONS: PTRs with pancreas allograft rejection and concomitant DSA have an increased risk of DCGF.

PMID:35427295 | DOI:10.1097/TP.0000000000004133

J Neuroophthalmol. 2022 Mar 25. doi: 10.1097/WNO.0000000000001554. Online ahead of print.

ABSTRACT

BACKGROUND: To identify the factors associated with visual prognosis for functional and structural outcomes of optic neuritis (ON) in patients with aquaporin-4-immunoglobulin (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD).

METHODS: We included the eyes that experienced at least 1 episode of ON and were followed for at least 2 years after the first attack of ON in patients with AQP4-IgG-positive NMOSD. We performed a retrospective review of clinical data, including ophthalmological examination and orbital MRI, of 34 eyes of 22 patients. Functional outcomes were measured as final visual acuity, visual field index, and mean deviation and structural outcomes as final retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness.

RESULTS: The mean age at onset of the first ON was 42.7 ± 13.7, and all patients were female. The poor visual acuity was significantly associated with the worse final visual acuity and thinner RNFL and GCIPL. Older age also showed a negative correlation with RNFL thickness. The number of attacks was not statistically significant for functional and structural outcomes. The lesion involving the intracanalicular optic nerve to the chiasm on orbital MRI showed worse visual acuity and a thinner GCIPL. Rapid high-dose intravenous methylprednisolone pulse therapy within 3 days was statistically significant, with better visual acuity and more preserved GCIPL thickness.

CONCLUSIONS: Our results indicate that the severity of ON rather than the number of recurrences might be critical for the visual prognosis of patients with AQP4-IgG-positive NMOSD. Rapid treatment within 3 days may improve visual outcomes, and a younger age at onset may have better visual outcomes.

PMID:35427249 | DOI:10.1097/WNO.0000000000001554

Expert Opin Investig Drugs. 2022 Apr 15. doi: 10.1080/13543784.2022.2067528. Online ahead of print.

ABSTRACT

BACKGROUND: Lenvatinib is a tyrosine kinase receptor inhibitor that inhibits vascular and endothelial growth factor receptor kinase activity. This study evaluated the bioequivalence and safety of lenvatinib developed by Chia Tai Tianqing Pharmaceutical Co., Ltd. with Lenvima® developed by Eisai Manufacturing Ltd.

RESEARCH DESIGN AND METHODS: The fasting and postprandial groups were two independent trials. There were 32 and 31 subjects in the fasting and postprandial groups, respectively. Subjects were randomly divided into two sequences at a ratio of 1:1 for two-cycle crossover administration. Subjects took 10 mg lenvatinib or Lenvima® once per cycle. The wash-out period was 14 days. Plasma drug concentrations were detected by specific liquid chromatography and tandem mass spectrometry (LC-MS/MS) assays. Statistical analysis of major pharmacokinetic (PK) parameters to assess drug bioequivalence was performed. In addition, we evaluated the safety of the drugs throughout the trial.

RESULTS: In the fasting state, the GMRs of C_max, AUC_0-t, and AUC_0-∞ were 99.89%, 102.98% and 103.19%, respectively. The 90% CIs were all within 80%-125%. In the postprandial state, the GMRs of C_max, AUC_0-t, and AUC_0-∞ were 98.96%, 94.25% and 95.27%, respectively. The 90% CIs were all within 80%-125%. All results met the bioequivalence criteria. Both drugs had good safety and tolerance in this trial.

CONCLUSION: This study showed that lenvatinib and Lenvima® had similar bioequivalence and safety in healthy Chinese subjects under fasting and postprandial conditions.

CLINICAL TRIAL REGISTRATION: This trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html # CTR20191172).

PMID:35427205 | DOI:10.1080/13543784.2022.2067528

J Clin Child Adolesc Psychol. 2022 Apr 15:1-16. doi: 10.1080/15374416.2022.2051524. Online ahead of print.

ABSTRACT

OBJECTIVE: To systematically review the prevalence of Attention Deficit Hyperactivity Disorder (ADHD) among Black children and adolescents compared to White, Latino and Asian children and adolescents.

METHOD: Peer-reviewed articles were identified in seven databases and included if they reported prevalence of ADHD among Black children and adolescents living in a minority context and compared rates to at least one of White, Latino or Asian samples. A total of 7050 articles were retrieved and 155 articles were subjected to full evaluation. Twenty-three studies representing 26 independent samples were included.

RESULTS: The pooled sample size was n = 218,445 (k = 26), n = 835,505 (k = 25), n = 493,417 (k = 24), and n = 66,413 (k = 7) of Black, White, Latino, and Asian participants, respectively. Pooled prevalence rate of ADHD was 15.9% (95%CI 11.6% – 20.7%) among Black children and adolescents, 16.6% (95%CI 11.6% – 22.2%) among Whites, 10.1% (95%CI 6.9% – 13.8%) among Latinos and 12.4% (95%CI 1.4% – 31.8%) among Asians. There was no significant difference in prevalence between ethnic groups, whereas both Black and White children and adolescents had marginally statistically significant higher prevalence than Asians. The results of a meta-regression analysis showed no moderating effects of the type of sample and the year of publication of studies. A significant publication bias was observed, suggesting that other moderators were not identified in the present systematic review.

CONCLUSION: In contrast to the assertion in the DSM-5 that clinical identification among Black children and adolescents is lower than among White children and adolescents, the present meta-analysis suggests similar rates of ADHD among these two groups. The importance of considering cultural appropriateness of assessment tools and processes is emphasized.

PMID:35427201 | DOI:10.1080/15374416.2022.2051524

Eval Rev. 2022 Apr 15:193841X221082887. doi: 10.1177/0193841X221082887. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Selecting applications for college admission is critical for university operation and development. This paper leverages machine learning techniques to support enrollment management teams through data-informed decision-making in this otherwise laborious admissions processing.

RESEARCH DESIGN AND MEASURES: Two aspects of university admissions are considered. An ensemble learning approach, through the SuperLearner algorithm, is used to predict student show (yield) rate. The goal is to improve prediction accuracy to minimize over- or under-enrollment. A combinatorial optimization framework is proposed to weigh academic performance and experiential factors for ranking and selecting students for admission. This framework uses simulated annealing, and an efficacy study is presented to evaluate performance.

RESULTS: The proposed framework is illustrated for selecting an incoming class by optimizing predicted graduation rate and by developing an eligibility index. Each example presents a selection process under potential academic performance and experiential factor targets a university may place on an admitted class. R code is provided for higher education researchers and practitioners to apply the proposed methods in their own settings.

PMID:35427199 | DOI:10.1177/0193841X221082887

Sci Immunol. 2022 Apr 15;7(70):eabl9165. doi: 10.1126/sciimmunol.abl9165. Epub 2022 Apr 15.

ABSTRACT

Inflammatory conditions represent the largest class of chronic skin disease, but the molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting the complex mixture of immune and stromal cell perturbations in inflammatory skin disease states. We single-cell-profiled CD45⁺ immune cell transcriptomes from skin samples of 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6 clinical/histopathologically indeterminate rashes, and 7 healthy controls). Our data revealed active proliferative expansion of the T_reg and Trm components and universal T cell exhaustion in human rashes, with a relative attenuation of antigen-presenting cells. Skin-resident memory T cells showed the greatest transcriptional dysregulation in both atopic dermatitis and psoriasis, whereas atopic dermatitis also demonstrated recurrent abnormalities in ILC and CD8⁺ cytotoxic lymphocytes. Transcript signatures differentiating these rash types included genes previously implicated in T helper cell (T_H2)/T_H17 diatheses, segregated in unbiased functional networks, and accurately identified disease class in untrained validation data sets. These gene signatures were able to classify clinicopathologically ambiguous rashes with diagnoses consistent with therapeutic response. Thus, we have defined major classes of human inflammatory skin disease at the molecular level and described a quantitative method to classify indeterminate instances of pathologic inflammation. To make this approach accessible to the scientific community, we created a proof-of-principle web interface (RashX), where scientists and clinicians can visualize their patient-level rash scRNA-seq-derived data in the context of our T_H2/T_H17 transcriptional framework.

PMID:35427179 | DOI:10.1126/sciimmunol.abl9165

Int J Gynaecol Obstet. 2022 Apr 15. doi: 10.1002/ijgo.14220. Online ahead of print.

ABSTRACT

OBJECTIVE: The main objective of this study was to describe the risk factors for immediate failure of gynecological outpatient surgery. The secondary objective was to describe the risk factors for re-hospitalization within 30 days after surgery.

METHODS: This is a single center retrospective cohort study conducted on all patients operated on in outpatient surgery in gynecology at the Lille University Hospital. The primary outcome was defined as any unanticipated admission to inpatient post-operative care unit on the day of the operation. The secondary outcome was defined as any rehospitalization within 30 days following the intervention. Our statistical analysis included 916 patients operated on between January and July 2019.

RESULTS: In our study, 84 patients (9.2%) had an immediate failure of outpatient surgery. The most frequent etiologies were surgical (58.3%). In multivariate analysis with logistic regression, the following variables were associated with an increased risk of immediate failure of outpatient surgery: urogynecologic surgery (P<0.001), complex laparoscopy (P=0.004), endometriosis surgery (P<0.001) and a duration of intervention longer than one hour (P<0.001).

CONCLUSION: We find an increased risk of immediate failure of gynecological outpatient surgery depending on the type of surgery as well as for surgeries lasting more than 1 hour.

PMID:35426951 | DOI:10.1002/ijgo.14220

Bioinformatics. 2022 Apr 15:btac273. doi: 10.1093/bioinformatics/btac273. Online ahead of print.

ABSTRACT

MOTIVATION: Targeted therapy for cancer-related genetic variants is critical for precision medicine. Although several databases including The Clinical Interpretation of Variants in Cancer (CIViC), The Oncology Knowledge Base (OncoKB), The Cancer Genome Interpreter (CGI), My Cancer Genome (MCG) provide clinical interpretations of variants in cancer, the clinical evidence was limited and miscellaneous. In this study, we developed the DrugCVar database, which integrated our manually curated cancer variant-drug targeting evidence from literature and the interpretations from the public resources.

RESULTS: In total, 7,830 clinical evidences for cancer variant-drug targeting were integrated and classified into ten evidence tiers. Searching and browsing functions were provided for quick queries of cancer variant-drug targeting evidence. Also, batch annotation module was developed for user-provided massive genetic variants in various formats. Details such as the mutation function, location of the variants in gene and protein structures, and mutation statistics of queried genes in various tumor types were also provided for further investigations. Thus, DrugCVar could serve as a comprehensive annotation tool to interpret potential drugs for cancer variants especially the massive ones from clinical cancer genomics studies.

AVAILABILITY AND IMPLEMENTATION: The database is available at http://drugcvar.omicsbio.info.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35426945 | DOI:10.1093/bioinformatics/btac273

Acta Neurochir (Wien). 2022 Apr 15. doi: 10.1007/s00701-022-05198-7. Online ahead of print.

ABSTRACT

OBJECTIVE: Quantitative data on visual outcomes after trans-sphenoidal surgery is lacking in the literature. This study aims to address this by quantitatively assessing visual field outcomes after endoscopic trans-sphenoidal pituitary adenectomy using the capabilities of modern semi-automated kinetic perimetry.

METHODS: Visual field area (deg²) calculated on perimetry performed before and after surgery was statistically analysed. Functional improvement was assessed against UK driving standards.

RESULTS: Sixty-four patients (128 eyes) were analysed (May 2016-Nov 2019). I4e and I3e isopter area significantly increased after surgery (p < 0.0001). Of eyes with pre-operative deficits: 80.7% improved and 7.9% worsened; the median amount of improvement was 60% (IQR 6-246%). Median increase in I4e isopter was 2213deg² (IQR 595-4271deg²) and in I3e isopter 1034 deg² (IQR 180-2001 deg²). Thirteen out of fifteen (87%) patients with III4e data regained driving eligibility after surgery. Age and extent of resection (EOR) did not correlate with visual improvement. Better pre-operative visual field area correlated with a better post-operative area (p < 0.0001). However, the rate of improvement in the visual field area increased with poorer pre-operative vision (p < 0.0001).

CONCLUSIONS: A median visual field improvement of 60% may be expected in over 80% of patients. Functionally, a significant proportion of patients can expect to regain driving eligibility. EOR did not impact on visual recovery. When the primary goal of surgery is alleviating visual impairment, optic apparatus decompression without the aim for gross total resection appears a valid strategy. Patients with the worst pre-operative visual field often experience the greatest improvement, and therefore, poor pre-operative vision alone should not preclude surgical intervention.

PMID:35426509 | DOI:10.1007/s00701-022-05198-7

Skeletal Radiol. 2022 Apr 15. doi: 10.1007/s00256-022-04055-z. Online ahead of print.

ABSTRACT

OBJECTIVE: To study the prevalence of suprapatellar fat pad (SPFP) MR alterations in asymptomatic subjects, in relation to a wide range of clinical/imaging parameters, including muscle performance tests and physical activity data.

MATERIALS AND METHODS: We prospectively included 110 asymptomatic subjects as part of a cohort study. Inclusion criteria were no knee pain in the last year. Exclusion criteria were any medical/surgical history of a knee disorder. Subjects underwent knee and low-dose posture radiographs [EOS®], 3 T MRI, clinical examination including muscle performance tests, and physical activity monitoring. The presence/absence of SPFP alterations (hyperintensity and mass effect) were assessed through consensus reading on fluid-sensitive sequences. Differences between groups of knees with SPFP alterations and controls were tested for a total of 55 categorical/continuous clinical/imaging parameters, including SPFP relative-T2-signal, trochlear/patellar/lower-limb morphologic measurements. Wilcoxon-rank-sum and chi-square tests were used to compare groups of patients. The histological correlation was obtained in a cadaveric specimen.

RESULTS: SPFP alterations were common in asymptomatic subjects: hyperintensity 57% (63/110) and mass effect 37% (41/110), with 27% (30/110) showing both. Among the 55 imaging, clinical, or activity parameters tested, only increased patellar tilt angle (p = 0.02) and TT-TG distance (p = 0.03) were statistically different between groups of SPFP alterations and controls. The histological correlation showed more abundant connective tissue in SPFP compared to the prefemoral fat pad.

CONCLUSIONS: SPFP hyperintensity and mass effect are common MRI findings in asymptomatic knees, and they are not related to most imaging, clinical, and activity parameters. Care should be taken not to overcall them pathological findings as they most likely represent normal variants.

PMID:35426502 | DOI:10.1007/s00256-022-04055-z