Nevin Manimala

J Pediatr Urol. 2021 Mar 19:S1477-5131(21)00126-1. doi: 10.1016/j.jpurol.2021.03.010. Online ahead of print.

ABSTRACT

INTRODUCTION: Minimally-invasive surgery (MIS) has been adopted slowly in pediatric oncology. We attempted to describe contemporary national trends in MIS use; we hypothesized that adolescents (who are more likely to have relatively small renal cell carcinomas) would have a higher proportion of MIS than younger children (who are more likely to have relatively large Wilms tumors) and that this relationship would vary by region.

OBJECTIVE: To explore whether pediatric urologic oncology outcomes vary by patient age or by surgical technique.

METHODS: We queried the 1998-2014 National Inpatient Sample (NIS) and included encounters in children aged ≤ 18 y, ICD-9 diagnostic code for renal tumor, and procedure code for open or MIS partial or radical nephrectomy. All analyses used weighted descriptive statistics and outcomes are compared based on age group (</>10 y) or surgery type; Wald-Chi square test was used for differences in proportions and unadjusted weighted ANOVA was used to test for differences in means.

RESULTS: 9259 weighted encounters were included; 91% were <10 years old and 50.7% were female. MIS surgery accounted for 1.8% of encounters; there was a difference in proportions by age group (1% <9 y vs. 9.9% >9 y, p < 0.01). The proportion of surgery type was similar across regions within age groups, however. Complications occurred in 13.3% of encounters; mean inpatient length of stay was 8.9 days (SD: 0.3); mean cost was $ 34,457.68 (SD: $1197.00). There was no evidence of a difference between surgery type and proportion of post-operative complications, mean inpatient length of stay or mean inpatient cost.

DISCUSSION: The admission-based, retrospective design of NIS left us unable to assess long-term outcomes, repeated admissions, or to track a particular patient across time; this is particularly relevant for oncologic variables on interest such as tumor stage or event-free survival. We were similarly limited in evaluating the effect of pre-surgical referral patterns on patient distributions.

CONCLUSION: In this preliminary descriptive analysis, MIS techniques were infrequently used in children, but there was a higher proportion of MIS use among adolescents. There were similar proportions of surgery type across geographic regions within the United States. Whether this infrequent usage is appropriate is as yet unclear given the lack of Level I evidence regarding the relative merits of MIS and open surgery for pediatric and adolescent renal tumors.

PMID:33849794 | DOI:10.1016/j.jpurol.2021.03.010

Cytokine. 2021 Apr 10:155522. doi: 10.1016/j.cyto.2021.155522. Online ahead of print.

ABSTRACT

Complement is an important branch of innate immunity; however, its biological significance goes far beyond the scope of simple nonspecific defense and involves a variety of physiological functions, including the adaptive immune response. In this review, to unravel the complex relationship between complement and tumors, we reviewed the high diversity of complement components in cancer and the heterogeneity of their production and activation pathways. In the tumor microenvironment, complement plays a dual regulatory role in the occurrence and development of tumors, affecting the outcomes of the immune response. We explored the differential expression levels of various complement components in human cancers via the Oncomine database. The gene expression profiling interactive analysis (GEPIA) tool and Kaplan-Meier plotter (K-M plotter) confirmed the correlation between differentially expressed complement genes and tumor prognosis. The tumor immune estimation resource (TIMER) database was used to statistically analyze the effect of complement on tumor immune infiltration. Finally, with a view to the role of complement in regulating T cell metabolism, complement could be a potential target for immunotherapies. Targeting complement to regulate the antitumor immune response seems to have potential for future treatment strategies. However, there are still many complex problems, such as who will benefit from this therapy and how to select the right therapeutic target and determine the appropriate drug concentration. The solutions to these problems depend on a deeper understanding of complement generation, activation, and regulatory and control mechanisms.

PMID:33849765 | DOI:10.1016/j.cyto.2021.155522

J Bone Joint Surg Am. 2021 Apr 21;103(8):668-680. doi: 10.2106/JBJS.20.01139.

ABSTRACT

BACKGROUND: The prevalence of nonunion after a proximal humeral fracture (PHF) and the risk factors for its occurrence are poorly defined. We aimed to estimate the rate of nonunion in nonoperatively treated patients and to produce a clinical model for its prediction.

METHODS: Two thousand two hundred and thirty adult patients (median age, 72 years [range, 18 to 103 years]; 75.5% were female) with a PHF underwent assessment of fracture union using standard clinical evaluation and conventional radiographs. We assessed the prevalence of nonunion and measured the effect of 19 parameters on healing. Best statistical practices were used to construct a multivariate logistic regression model. The PHF assessment of risk of nonunion model (PHARON) was externally validated in a subsequent prospectively collected population of 735 patients, treated by the same protocol in our institution.

RESULTS: Overall, 231 (10.4%) of 2,230 patients developed nonunion. Only 3 (0.8%) of 395 patients with a head-shaft angle (HSA) of >140° developed nonunion; in this cohort, none of the measured candidate variables were independently predictive of nonunion on multivariate logistic regression analysis. In the larger cohort of 1,835 patients with an HSA of ≤140°, 228 (12.4%) developed nonunion. Decreasing HSA, increasing head-shaft translation (HST), and smoking were independently predictive of nonunion on multivariate analysis. The prevalence of nonunion was very low (1%) in the majority with both an HSA of >90° and HST of <50%, whereas the risk was much higher (83.7%) in the 8.3% with an HSA of ≤90° and HST of ≥50%. In both groups, the prevalence of nonunion was much higher in smokers.

CONCLUSIONS: The prevalence of nonunion after PHF is higher than previously reported. Most patients have favorable risk-factor estimates and a very low risk of this complication, but a smaller subgroup is at much higher risk. The risk can be accurately estimated with PHARON, using standard clinical assessment tools.

LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

PMID:33849049 | DOI:10.2106/JBJS.20.01139

Respiration. 2021 Apr 13:1-9. doi: 10.1159/000515335. Online ahead of print.

ABSTRACT

BACKGROUND: In idiopathic pulmonary fibrosis (IPF), some physiological parameters measured during a 6-min walk test (6-MWT) impart reliable prognostic information. Sit-to-stand tests (STSTs) are field exercise tests that are easier to implement than the 6-MWT in daily practice.

OBJECTIVES: The aims of the study were to test the reproducibility and compare 2 STSTs (the 1-min STST [1-STST] and the semi-paced 3-min chair rise test [3-CRT]) in IPF, and to determine if selected physiological parameters (speed of displacement and changes in pulse oxygen saturation [SpO2]) are interchangeable between the STSTs and the 6-MWT.

METHODS: Thirty-three patients with stable IPF were studied in 3 French expert centers. To test reproducibility, intra-class correlations (ICCs) of parameters measured during tests performed 7-14 days apart were calculated. To test interchangeability, the agreement and correlation of physiological responses measured during STSTs and during 6-MWT were studied.

RESULTS: Vertical displacements and changes in SpO2 during both STSTs were reproducible, with ICCs ranging from 0.78 [0.63-0.87] to 0.95 [0.92-0.97]. Vertical displacements during 1-STST and 3-CRT were correlated with 6-MWT distance (correlation coefficients (r) of 0.72 and 0.77, respectively; p < 0.001). Similarly, correlations were found between changes in SpO2 measured during the 2 STSTs and the 6-MWT, with coefficients ranging from 0.73 to 0.91 (p < 0.001). Distance walked and SpO2 during 6-MWT were well estimated from vertical displacement and SpO2 during the 2 STSTs, respectively.

CONCLUSION: The correlations found between the 2 STSTs and the 6-MWT suggest that STSTs may be of interest to assess displacement and exercise-induced changes in SpO2 in IPF patients.

PMID:33849043 | DOI:10.1159/000515335

Cerebrovasc Dis. 2021 Apr 13:1-6. doi: 10.1159/000515320. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Randomized controlled trials have demonstrated the importance of time to endovascular therapy (EVT) in clinical outcomes in large vessel occlusion (LVO) acute ischemic stroke. Delays to treatment are particularly prevalent when patients require a transfer from hospitals without EVT capability onsite. A computer-aided triage system, Viz LVO, has the potential to streamline workflows. This platform includes an image viewer, a communication system, and an artificial intelligence (AI) algorithm that automatically identifies suspected LVO strokes on CTA imaging and rapidly triggers alerts. We hypothesize that the Viz application will decrease time-to-treatment, leading to improved clinical outcomes.

METHODS: A retrospective analysis of a prospectively maintained database was assessed for patients who presented to a stroke center currently utilizing Viz LVO and underwent EVT following transfer for LVO stroke between July 2018 and March 2020. Time intervals and clinical outcomes were compared for 55 patients divided into pre- and post-Viz cohorts.

RESULTS: The median initial door-to-neuroendovascular team (NT) notification time interval was significantly faster (25.0 min [IQR = 12.0] vs. 40.0 min [IQR = 61.0]; p = 0.01) with less variation (p < 0.05) following Viz LVO implementation. The median initial door-to-skin puncture time interval was 25 min shorter in the post-Viz cohort, although this was not statistically significant (p = 0.15).

CONCLUSIONS: Preliminary results have shown that Viz LVO implementation is associated with earlier, more consistent NT notification times. This application can serve as an early warning system and a failsafe to ensure that no LVO is left behind.

PMID:33849032 | DOI:10.1159/000515320

Pediatr Neurosurg. 2021 Apr 13:1-10. doi: 10.1159/000515038. Online ahead of print.

ABSTRACT

OBJECTIVE: We sought to compare our large single-institution cohort of postnatal myelomeningocele closure to the 2 arms of the Management of Myelomeningocele Study (MOMS) trial at the designated trial time points, as well as assess outcomes at long-term follow-up among our postnatal cohort.

METHODS: A single-institutional retrospective review of myelomeningocele cases presenting from 1995 to 2015 at Children’s Hospital of Pittsburgh was performed. We compared outcomes at 12 and 30 months to both arms of the MOMS trial and compared our cohort’s outcomes at those designated time points to our long-term outcomes. Univariate statistical analysis was performed as appropriate.

RESULTS: One-hundred sixty-three patients were included in this study. All patients had at least 2-year follow-up, with a mean follow-up of 10 years (range 2-20 years). There was no difference in the overall distribution of anatomic level of defect. Compared to our cohort, the prenatal cohort had a higher rate of tethering at 12 months of age, 8 versus 1.8%. Conversely, the Chiari II decompression rate was higher in our cohort (10.4 vs. 1.0%). At 30 months, the prenatal cohort had a higher rate of independent ambulation, but our cohort demonstrated the highest rate of ambulation with or without assistive devices among the 3 groups. When comparing our cohort at these early time points to our long-term follow-up data, our cohort’s ambulatory function decreased from 84 to 66%, and the rate of detethering surgery increased almost 10-fold.

CONCLUSIONS: This study demonstrated that overall ambulation and anatomic-functional level were significantly better among our large postnatal cohort, as well as having significantly fewer complications to both fetus and mother, when compared to the postnatal cohort of the MOMS trial. Our finding that ambulatory ability declined significantly with age in this patient population is worrisome for the long-term outcomes of the MOMS cohorts, especially given the high rates of cord tethering at early ages within the prenatal cohort. These findings suggest that the perceived benefits of prenatal closure over postnatal closure may not be as substantial as presented in the original trial, with the durability of results still remaining a concern.

PMID:33849030 | DOI:10.1159/000515038

Dermatology. 2021 Apr 13:1-8. doi: 10.1159/000515158. Online ahead of print.

ABSTRACT

BACKGROUND: Mobile teledermoscopy is an emerging technology that involves imaging and digitally sending dermoscopic images of skin lesions to a clinician for assessment. High-quality, consistent images are required for accurate telediagnoses when monitoring lesions over time. To date there are no tools to assess the quality of sequential images taken by consumers using mobile teledermoscopy. The purpose of this study was to develop a tool to assess the quality of images acquired by consumers.

METHODS: Participants imaged skin lesions that they felt were concerning at baseline, 1-, and 2-months. A checklist to assess the quality of consumer sequential imaging of skin lesions was developed based on the International Skin Imaging Collaboration guidelines. A scale was implemented to grade the quality of the images: 0 (low) to 18 (very high). Intra- and inter-reliability of the checklist was assessed using Bland-Altman analysis. Using this checklist, the consistency with which 85 sets of images were scored by 2 evaluators were compared using Kappa statistics. Items with a low Kappa value <0.4 were removed.

RESULTS: After reliability testing, 5 of the items were removed due to low Kappa values (<0.4) and the final checklist included 13 items surveying: lesion selection; image orientation; lighting; field of view; focus and depth of view. Participants had a mean age of 41 years (range 19-73), and 67% were female. Most participants (84%, n = 71/85) were able to select and image the correct lesion over time for both the dermoscopic and overview images. Younger participants (<40 years old) scored significantly higher (8.1 ± 2.1) on the imaging checklist compared to older participants (7.1 ± 2.4; p = 0.037). Participants had most difficulty with consistent image orientation.

CONCLUSIONS: This checklist could be used as a triage tool to filter images acquired by consumers prior to telediagnosis evaluation, which would improve the efficiency and accuracy of teledermatology and teledermoscopy processes. It may also be used to provide feedback to the consumers to improve image acquisition over time.

PMID:33849022 | DOI:10.1159/000515158

Gerontology. 2021 Apr 13:1-9. doi: 10.1159/000515161. Online ahead of print.

ABSTRACT

INTRODUCTION: The Multidimensional Prognostic Index (MPI) is a validated tool for assessing mortality risk in hospitalised patients. We aimed to evaluate whether the MPI predicted mortality and the risk of developing diverticular disease (DD) complications in older patients.

METHODS: This is a multicentre study conducted in January 2016-March 2018. All patients with DD aged 65 years and older were included. Patients were stratified into three groups according to MPI groups (1, low risk; 2, moderate risk; 3, high risk). Risk of developing DD complications and mortality rate were assessed. Bivariate models were fitted.

RESULTS: One hundred hospitalised patients with DD (mean age 77.9 ± 10.6 years, 53 female patients) were included. Patients with higher MPI groups were more likely to develop DD complications. In particular, 12 (46.2%), 21 (52.5%), and 28 (82.4%) patients with complicated DD were distributed to the MPI 1, MPI 2, and MPI 3 groups (p = 0.0063), respectively. Two patients died in the MPI 1, 4 in the MPI 2, and 29 in the MPI 3 group, with mortality rates of 4.0 per 100 person-year (95% confidence interval [CI] 1.0-15.9), 5.6 (95% CI 2.1-15.0), and 89.2 (95% CI 62-130), respectively (log-rank test p < 0.001). In bivariate analysis, after adjustment for age >80 years, Charlson Comorbidity Index >4, DD complications, and the presence of thromboembolism, higher MPI group was independently associated with higher mortality. Those in the MPI 3 group experienced a greater risk of 1-year hospital readmission (p < 0.001).

CONCLUSION: MPI predicted mortality in patients with DD and also correlated with the risk of developing DD complications. Studies focussing on possible pathophysiological mechanisms between DD complications and MPI are needed.

PMID:33849017 | DOI:10.1159/000515161

Acta Haematol. 2021 Apr 13:1-9. doi: 10.1159/000514907. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to determine the expression of G protein-coupled receptors (GPCRs) in platelets from adult patients with chronic immune thrombocytopenic purpura (ITP).

METHODS: Peripheral blood samples were collected from 40 patients with chronic ITP in the Second Affiliated Hospital of Shantou University Medical College, and 40 peripheral blood samples from healthy volunteers were collected; expressions of the adenosine diphosphate receptors (P2Y1 and P2Y12), alpha-2A adrenergic receptor (α2A-AR), and thromboxane A2 receptor (TP) in platelets were detected by flow cytometry. Gα protein, protease-activated receptor 1 (PAR1), and protease-activated receptor 4 (PAR4) were analyzed by Western blot and analyzed statistically.

RESULTS: Flow cytometry measurements of mean fluorescence intensities showed platelets from patients with chronic ITP, compared to healthy individuals, had significantly higher levels of P2Y1 (31.4 ± 2.2 vs. 7.8 ± 0.8), P2Y12 (29.6 ± 2.1 vs. 7.2 ± 1.3), α2A-AR (25.8 ± 2.9 vs. 9.8 ± 0.9), and TP (39.8 ± 3.1 vs. 4.7 ± 0.6) (all p < 0.01). Similarly, integrated optical density analysis of Western blots showed that platelets from patients with chronic ITP had significantly higher levels of Gα (1046.3 ± 159.96 vs. 254.49 ± 39.51), PAR1 (832.98 ± 98.81 vs. 203.92 ± 27.47), and PAR4 (1518.80 ± 272.45 vs. 431.27 ± 41.86) (all p < 0.01).

CONCLUSION: Expression of GPCRs is increased in platelets from patients with chronic ITP, suggesting that platelets of chronic ITP may participate in the complicated biological process by means of GPCR-mediated signaling pathways.

PMID:33849009 | DOI:10.1159/000514907

J Neural Eng. 2021 Apr 13. doi: 10.1088/1741-2552/abf772. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the viability of developing a computer-aided diagnostic system for Parkinsonian syndromes using dynamic [11C]raclopride PET and T1-weighted MRI data.

APPROACH: The biological heterogeneity of Parkinsonian syndromes renders their statistical classification a challenge. The unique combination of structural and molecular imaging data allowed different classifier designs to be tested. Datasets from dynamic [11C]raclopride PET and T1-weighted MRI scans were acquired from six groups of participants: healthy controls (CTRL n=15), patients with Parkinson’s disease (PD n=27), multiple system atrophy (MSA n=8), corticobasal degeneration (CBD n=6), and dementia with Lewy bodies (DLB n=5). MSA, CBD, and DLB patients were classified into one category designated as atypical parkinsonism (AP). The distribution volume ratio (DVR) kinetic parameters obtained from PET data were used to quantify the reversible tracer binding to D2/D3 receptors in the subcortical regions of interest (ROI). Grey matter (GM) volumes obtained from the MRI data were used to quantify GM atrophy across cortical, subcortical, and cerebellar ROI.

RESULTS: The classifiers CTRL vs PD and CTRL vs AP achieved the highest balanced accuracy combining DVR and GM (DVR-GM) features (96.7%, 92.1%, respectively), followed by the classifiers designed with DVR features (93.3%, 88.8%, respectively), and GM features (69.6%, 86.1%, respectively). In contrast, the classifier PD vs AP showed the highest balanced accuracy (78.9%) using DVR features only. The integration of DVR-GM (77.9%) and GM features (72.7%) produced inferior performances. The classifier CTRL vs PD vs AP showed high weighted balanced accuracy when DVR (80.5%) or DVR-GM features (79.9%) were integrated. GM features revealed poorer performance (59.5%).

SIGNIFICANCE: This work was unique in its combination of structural and molecular imaging features in binary and triple category classifications. We were able to demonstrate improved binary classification of healthy/diseased status (concerning both PD and AP) and equate performance to DVR features in multiclass classifications.

PMID:33848996 | DOI:10.1088/1741-2552/abf772