Nevin Manimala

Immun Inflamm Dis. 2021 Jul 26. doi: 10.1002/iid3.491. Online ahead of print.

ABSTRACT

PURPOSE: Induction immunosuppression has improved the long-term outcomes after lung transplant. This is the first report exploring the association of induction immunosuppression with the development of de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) in lung transplant recipients (LTR).

METHODS: Sixty-seven consecutive primary LTR were followed for 3 years posttransplant. A total of 41/67 (61%) LTR-received induction immunosuppression using a single dose of rabbit Antithymocyte Globulin (rATG; 1.5 mg/kg) within 24 h of transplant. All recipients had a negative flow cytometry crossmatch on the day of transplant. Serum samples at 1, 3, 6, and 12 months posttransplant were assessed for the presence of de novo HLA DSA.

RESULTS: De novo HLA DSA were detected in 22/67 (32.8%) LTR within 1-year posttransplant. Of these, 9/41 (21.9%) occurred in the induction therapy group and 13/26 (50%) in the noninduction group. Class II DSA were detected in 3/41 (7.3%) LTR who received induction compared to 9/26 (34.6%) LTR without induction immunosuppression (p = .005). Differences in overall survival or freedom from chronic lung allograft dysfunction rates between the two groups were not statistically significant.

CONCLUSION: Induction immunosuppression utilizing a modified regimen of single-dose rATG is associated with a significant reduction in de novo DSA production in LTR.

PMID:34310850 | DOI:10.1002/iid3.491

Colorectal Dis. 2021 Jul 26. doi: 10.1111/codi.15836. Online ahead of print.

ABSTRACT

AIM: To investigate the conflicting consequences of faecal diversion on stoma outcomes and anastomotic leakage in anterior resection for rectal cancer, including interaction effects determined by the extent of mesorectal excision.

METHOD: Anterior resections between 2007 and 2016 were identified using the Swedish Colorectal Cancer Registry. National Patient Registry data were added to determine stoma outcome two years after surgery. Tumour distance from the anal verge constituted a proxy for extent of mesorectal excision [total mesorectal excision (TME): ≤ 10 cm; partial mesorectal excision (PME): 13-15 cm]. With confounder-adjusted probit regression, the total effect of defunctioning stoma on permanent stoma, and the interaction effect of extent of mesorectal excision, were estimated together with the indirect effect through anastomotic leakage. Baseline risks, risk differences (RDs) and relative risks (RRs) were reported.

RESULTS: The main study cohort included 4529 patients. Defunctioning stomas influenced the absolute permanent stoma risk [TME: RD 0.11 (95% CI 0.09-0.13); PME: RD 0.15 (95% CI 0.13-0.16)]. The baseline risk was higher in TME, with a resulting greater RR in PME [2.23 (95% CI 1.43-3.02) vs 4.36 (95% CI 3.05-5.68)]. The indirect reduction in permanent stoma rates, due to the alleviating effect of faecal diversion on anastomotic leakage, was small [TME: 0.89 (95% CI 0.81-0.96); PME: 0.96 (95% CI 0.91-1.00)].

CONCLUSION: In anterior resection for rectal cancer, defunctioning stomas may reduce chances of a stoma-free outcome. Considering leakage reduction benefits, consequences of routine diversion in TME might be fairly balanced, while this seems questionable in PME.

PMID:34310840 | DOI:10.1111/codi.15836

Int J Clin Pract. 2021 Jul 26:e14652. doi: 10.1111/ijcp.14652. Online ahead of print.

ABSTRACT

OBJECTIVE: Pediatric patients are highly exposed to medication errors especially dosing errors. This study assessed the community pharmacists’ knowledge about appropriate dosing of antibiotics among pediatric patients, factors affecting community pharmacists’ knowledge, and barriers that lead to inappropriate dosing of antibiotics.

METHODS: A self-administered questionnaire was distributed to 1283 Jordanian pharmacists who worked in community pharmacies. Descriptive statistics and multivariate regression were conducted.

RESULTS: The response rate was 87.1%. The majority of pharmacists (86.4%) were non-knowledgeable about appropriate dosing of antibiotics among pediatrics. The monthly income of the pharmacist was positively associated with pharmacists’ knowledge. The case of azithromycin dosing in acute bacterial pharyngitis was answered correctly by the highest percentage of community pharmacists (55.8%) while the case of trimethoprim-sulfamethoxazole dosing in lower urinary tract infection was answered correctly by the lowest percentage (15.7%). Poor scientific knowledge about dose calculation was the most reported barrier by the participants (54.7%).

CONCLUSION: Most community pharmacists were non-knowledgeable about appropriate dosing of antibiotics in pediatrics and the level of knowledge was affected by monthly income. Implementing adequate and appropriate educational programs, constructing specific guidelines that regulate antibiotics practice among community pharmacists are highly recommended.

PMID:34310826 | DOI:10.1111/ijcp.14652

Ann Noninvasive Electrocardiol. 2021 Jul 26:e12880. doi: 10.1111/anec.12880. Online ahead of print.

ABSTRACT

BACKGROUND: Several ECG criteria have been widely used for diagnosis of left ventricular hypertrophy (LVH) in clinical practice. However, their performance in a general Chinese population is limited.

METHODS AND RESULTS: A multi-stage, stratified cluster sampling across China was performed and 7415 representative Chinese adults aged 18-85 years were analyzed. ECG was collected by using GE MAC 5500 machine. The association between five ECG-LVH criteria (i.e., Peguero-Lo Presti, Cornell, Cornell product, Sokolow-Lyon and Sokolow-Lyon product) and echocardiographic LVH (Echo-LVH) was assessed by Pearson’s correlation, diagnostic statistics like predictive values, and receiver operating characteristics (ROC) curve. We found that the prevalence of the Echo-LVH was 11% while ECG-LVH ranged from 3% to 27%. All ECG-LVH criteria had high negative predictive value (NPV) (89%) and specificity (73-96%) but low positive predictive value (PPV) (12-24%) and sensitivity (4-29%). The newly Peguero-Lo Presti criteria had higher sensitivity (29%) but lower specificity (73%) and accuracy (68%) compared with other criteria. Cornell product had the best diagnostic performance (AUC: 0.59), as well as the highest specificity (96%) and accuracy (86%) but lowest sensitivity (4%). Among single-lead components of ECG criteria, R_aVL voltage and QRS duration performed relatively better than others. Hypertensive and older individuals had higher sensitivity but lower specificity and accuracy than their counterparts.

CONCLUSION: ECG-LVH criteria had high NPV to detect Echo-LVH. Though with higher sensitivity, Peguero-Lo Presti criteria did not have better diagnostic performance to detect Echo-LVH. R_aVL and QRS duration had stronger association with Echo-LVH among all single-lead components.

PMID:34310813 | DOI:10.1111/anec.12880

J Prosthodont. 2021 Jul 26. doi: 10.1111/jopr.13406. Online ahead of print.

ABSTRACT

PURPOSE: Error testing at each stage of prosthetic manufacturing remains relatively underdeveloped for computer-aided design/computer-aided manufacturing methods, and no experimental studies have validated the computer-aided design programs. This study aimed to test the accuracy and trueness of the computer-aided design of a three-unit fixed prosthesis.

MATERIALS & METHODS: Three computer-aided design programs (Exocad, Dental System™, and inLab 16) were tested on the designs of a three-unit fixed partial denture, and a three-dimensional analysis program was used to calculate the internal clearance error for the computer-aided design prostheses. The Kruskal-Wallis and Dunn’s post hoc tests were used to reveal significant differences in trueness between the three computer-aided design programs (α<0.05).

RESULTS: Dental System™ showed the lowest mean error values for #24 and #26 at the mesial margin (both 0 μm), mesial wall (0.10, 0.12 μm, respectively), occlusal surface (-0.05, 0.10 μm), distal wall (0.23, -0.02 μm), and distal margin (both 0 μm). In sum, except for the mesial margin and distal margin site of tooth #26, the mean error value of Dental System™ was statistically the lowest, followed by those of Exocad and inLab 16 (p<0.003).

CONCLUSIONS: The accuracy of computer-aided design differed according to the type of computer-aided design program: Dental System™ achieved the best trueness at the margins, axial walls, and occlusal surface, followed by Exocad and inLab 16. This article is protected by copyright. All rights reserved.

PMID:34310790 | DOI:10.1111/jopr.13406

Transpl Int. 2021 Jul 26. doi: 10.1111/tri.13994. Online ahead of print.

ABSTRACT

With this issue, Transplant International (TI) reveals its new attires! A new logo, a new cover page design and a new style accompany a re-branding effort by ESOT, but also denote the new spirit and the new strategic positioning of our journal.

PMID:34310784 | DOI:10.1111/tri.13994

Pediatr Allergy Immunol. 2021 Jul 26. doi: 10.1111/pai.13605. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood allergic rhinitis (AR) is clinically heterogeneous. We aimed to identify distinct phenotypes amongst children with AR using data-driven techniques, and to ascertain their association with patterns of symptoms, allergic sensitization and comorbidities.

METHODS: We recruited 510 children with physician-diagnosed AR, of whom 205 (40%) had asthma. Latent class analysis (LCA) was performed to identify latent structure within the data set using 17 variables (allergic conjunctivitis, eczema, asthma, family history of asthma, family history of allergic rhinitis, skin sensitization to 8 common allergens, tonsillectomy, adenoidectomy).

RESULTS: A four-class solution was selected as the optimal model based on statistical fit. We labeled latent classes as: (1) AR with grass mono-sensitization and conjunctivitis (n=361, 70.8%); (2) AR with house dust mite sensitization and asthma (n=75, 14.7%); (3) AR with pet and grass polysensitization and conjunctivitis (n=35, 6.9%) and (4) AR among children with tonsils and adenoids removed (n=39, 7.6%). Perennial AR was significantly more common among children in Class 2 (OR 5.83, 95%CI 3.42-9.94, p<0.001) and Class 3 (OR 2.88, 95%CI 1.36-6.13, p=0.006). Mild and intermittent AR symptoms were significantly more common in children in Class 2 compared to those in Class 1. AR was more severe in Class 1 compared to other 3 classes, indicating that upper respiratory symptoms are more severe among children with isolated seasonal rhinitis, than in those with rhinitis and coexisting asthma.

CONCLUSION: We have identified 4 phenotypes in school-age children with AR, which were associated with different patterns of clinical symptoms and comorbidities.

PMID:34310772 | DOI:10.1111/pai.13605

J Eur Acad Dermatol Venereol. 2021 Jul 26. doi: 10.1111/jdv.17533. Online ahead of print.

ABSTRACT

Therapeutic options for patients with metastatic melanoma have greatly improved with the introduction of immune checkpoint-inhibition (ICI) and targeted therapies (TT).(1-4) However, a substantial proportion of patients does not respond or experiences toxicities. Thus, prognostic and predictive biomarkers including metabolic host factors are needed. The modified Glasgow-prognostic-score (mGPS) is a well-established immuno-nutritional prognostic assessment in various cancers(5-8), but not yet assessed in melanoma.

PMID:34310762 | DOI:10.1111/jdv.17533

J Surg Oncol. 2021 Jul 26. doi: 10.1002/jso.26618. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Pancreatic neuroendocrine tumors (pNETs) in patients with hereditary cancer syndromes are typically multifocal. In contrast, sporadic pNETs are usually unifocal and the incidence of multifocal sporadic pNETs is unknown. The primary aim of this study was to investigate the incidence of multifocality in sporadic pNETs and any associated effect on recurrence risk and survival.

METHODS: Patients who underwent resection of pNETs at Mayo Clinic from 2000 to 2019 were identified and clinical data were obtained from medical records. Syndromic disease was defined as pNETs arising in the setting of a hereditary cancer syndrome. Statistical comparisons were made using χ² , Fisher’s exact, and Kruskal-Wallis tests and survival was assessed using the Kaplan-Meier method.

RESULTS: Six hundred and sixty-one patients with sporadic pNETs and fifty-nine with syndromic pNETs were identified. Multifocal disease was present in 4.8% of sporadic patients and 84.7% of syndromic patients (p < .001). Within patients with sporadic pNETs, clinicopathologic features and recurrence-free and overall survival were similar between patients with unifocal and multifocal disease.

CONCLUSIONS: Multifocal sporadic pNETs are rare and multifocality is not associated with worse survival or increased recurrence risk. Patients with multifocal sporadic pNETs can likely be safely managed with a combination of resection and observation as indicated for each tumor.

PMID:34310723 | DOI:10.1002/jso.26618

Int J Cancer. 2021 Jul 26. doi: 10.1002/ijc.33747. Online ahead of print.

ABSTRACT

Secondary resection of metastases is recommended in metastatic colorectal cancer (mCRC). Data describing changes in mutational profiles of corresponding primary tumor and metastatic tissue after conversion treatment are limited. Next generation sequencing was performed in formalin-fixed mCRC samples from patients of the FIRE-3 trial (FOLFIRI plus cetuximab or bevacizumab) before treatment start (baseline) and after secondary resection of metastases (post baseline). Changes of mutational profiles and tumor mutational burden (TMB) were assessed within a post-hoc analysis. Median overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were compared between treatment arms. Paired tumor samples were obtained from 25 patients (19 RAS wild-type, 6 RAS mutant by pyrosequencing). ORR (92.0% vs 58.0%) and OS (60.8 vs 35.4 months, hazard ratio = 0.39 [95% CI 0.14-1.12], P = 0.08) were higher for patients receiving cetuximab. After conversion therapy, 56 alterations (42 in the cetuximab and 14 in the bevacizumab arm) were newly observed in 18 patients (9 each treated with cetuximab or bevacizumab). Gains (n = 21) and losses (n = 21) of alterations occurred during cetuximab-based treatment, while mainly gains of alterations occurred during bevacizumab (n = 10). Three of nine patients treated with cetuximab that presented a change of mutational profiles, developed resistance to cetuximab. Mutational profiles were largely comparable before and after treatment with anti-VEGF or anti-EGFR directed monoclonal antibodies after secondary resection. Mutations associated with resistance to anti-EGFR antibodies were observed in only one third of patients.

PMID:34310714 | DOI:10.1002/ijc.33747