Nevin Manimala

Clin Exp Rheumatol. 2022 Jul 11. doi: 10.55563/clinexprheumatol/5epyh7. Online ahead of print.

ABSTRACT

OBJECTIVES: Biologic disease-modifying anti-rheumatic drugs (b-DMARDs) have qualitatively improved the management of axial spondyloarthritis (axSpA), but up to 30-40% of patients do not respond. Although lymphocytes are clearly implicated in the pathology of SpA, circulating lymphocyte subsets (LS) dynamics has been poorly studied. The objective of this pilot study was to comprehensively analyse circulating LS abnormalities in axSpA, and to determine their potential association with response to b-DMARDs.

METHODS: Sixty-nine patients with axSpA and 141 control subjects (HC) were included. The clinical features were measured at baseline, and additionally at 6 months in a subgroup of patients who received TNFi (n=36) or IL17i (n=26). Clinical response was defined as a 50% reduction of BASDAI or decrease in ASDAS of 1.1 point. CD4/CD8 T-cells, B-cells and NK-cells and their subsets were analysed by flow cytometry at inclusion.

RESULTS: At baseline, alterations in LS were observed in axSpA with reduced/increased frequencies of 10/27 subsets (p<0.003 after correction) and trends for another 5. There was no association of response to bDMARDs with clinical data. Response to IL17i (61% cases) was associated with a higher frequency of NK-cells (p=0.003), trends for change in naïve/memory-CD8+T-cells (p<0.055) and increased expression of KIR3DL2 on Th17-cells (p=0.052). No LS was associated with response to TNFi (69% cases) although trends were observed (CD4+T-cells subsets, higher IL-6R on CD4+/CD8+T-cells).

CONCLUSIONS: This pilot work demonstrated a dysregulation of LS in axSpA. The association observed between several LS and clinical response to IL17i (NK/CD8 subsets/Th17-KIR3DL2) was very different to that observed for TNFi (CD4/IL-6R).

PMID:35819806 | DOI:10.55563/clinexprheumatol/5epyh7

Clin Exp Rheumatol. 2022 Jul 11. doi: 10.55563/clinexprheumatol/0gs167. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine whether early damage and its kinetics measured by the Damage Index for Antiphospholipid Syndrome (DIAPS) predicts mortality.

METHODS: We carried out a single-centre retrospective analysis of thrombotic APS patients (2006 Sydney criteria), using the DIAPS for damage assessment. Early damage was considered to be at six months after disease onset; early damage increase (delta-DIAPS) was deemed to be at least a one-point rise in DIAPS within the first five years of illness. Groups were compared using appropriate statistical tests. Survival was analysed by the Kaplan-Meier method. Cox regression analysis was performed to investigate predictors of mortality.

RESULTS: A total of 197 patients (71.1% female; 65.9% primary APS; 72.4% Caucasian) were followed for up to 43 years (median 10). Damage developed in 143 (73.6%) patients. Twenty-three patients (12%) died. Secondary APS (HR 3.07, 95%CI 1.32-7.12, p=0.009), male sex (HR 3.14, 95%CI 1.35-7.33, p=0.008) and age at APS onset ≥40 years (HR 5.34, 95%CI 1.96-14.53, p=0.001) were risk factors for death. Early damage (n=69, 35.0%) was not associated with death (p=0.231). Having a first arterial event was associated with early damage (p<0.001), but not with delta-DIAPS (p=0.539) nor with the risk of death (p=0.151). Delta-DIAPS (n=53/181, 29.3%) predicted mortality (HR 5.40, 95%CI 2.33-12.52, p<0.001), even after adjusting individually for APS category (secondary), sex (male), early damage and age at APS onset (≥40 years) (all p<0.005).

CONCLUSIONS: Evolving damage in the first five years of illness, but not early damage, predicted mortality regardless of the nature of the first thrombotic event, sex, APS category and age.

PMID:35819804 | DOI:10.55563/clinexprheumatol/0gs167

Acta Orthop. 2022 Jul 5;93:634-642. doi: 10.2340/17453674.2022.3909.

ABSTRACT

BACKGROUND AND PURPOSE: Developing meaningful thresholds for the Oxford Knee Score (OKS) advances its clinical use. We determined the minimal important change (MIC), patient acceptable symptom state (PASS), and treatment failure (TF) values as meaningful thresholds for the OKS at 3-, 12-, and 24-month follow-up in patients undergoing unicompartmental knee arthroplasty (UKA).

PATIENTS AND METHODS: This is a cohort study with data from patients undergoing UKA collected at a hospital in Denmark between February 2016 and September 2021. The OKS was completed preoperatively and at 3, 12, and 24 months postoperatively. Interpretation threshold values were calculated with the anchor-based adjusted predictive modeling method. Non-parametric bootstrapping was used to derive 95% confidence intervals (CI).

RESULTS: Complete 3-, 12-, and 24-month postoperative data was obtained for 331 of 423 (78%), 340 of 479 (71%), and 235 of 338 (70%) patients, median age of 68-69 years (58-59% females). Adjusted OKS MIC values were 4.7 (CI 3.3-6.0), 7.1 (CI 5.2-8.6), and 5.4 (CI 3.4- 7.3), adjusted OKS PASS values were 28.9 (CI 27.6-30.3), 32.7 (CI 31.5-33.9), and 31.3 (CI 29.1-33.3), and adjusted OKS TF values were 24.4 (CI 20.7-27.4), 29.3 (CI 27.3-31.1), and 28.5 (CI 26.0-30.5) at 3, 12, and 24 months postoperatively, respectively. All values statistically significantly increased from 3 to 12 months but not from 12 to 24 months.

INTERPRETATION: The UKA-specific measurement properties and clinical thresholds for the OKS can improve the interpretation of UKA outcome and assist quality assessment in institutional and national registries.

PMID:35819794 | DOI:10.2340/17453674.2022.3909

JAMA Netw Open. 2022 Jul 1;5(7):e2220696. doi: 10.1001/jamanetworkopen.2022.20696.

ABSTRACT

IMPORTANCE: The effect of pediatric advance care planning (pACP) on the sustainability of end-of-life treatment preference congruence between adolescents with cancer and their families has not been examined.

OBJECTIVE: To evaluate the longitudinal efficacy of the Family-Centered Advance Care Planning for Teens with Cancer (FACE-TC) intervention to sustain adolescent-family congruence about end-of-life treatment preferences.

DESIGN, SETTING, AND PARTICIPANTS: This multisite, assessor-blinded, randomized clinical trial enrolled adolescents with cancer (aged 14-21 years) and their family members from 4 pediatric hospitals between July 16, 2016, and April 30, 2019. Participants were randomized 2:1 to FACE-TC (intervention group) or treatment as usual (control group) and underwent 5 follow-up visits over an 18-month postintervention period. Intention-to-treat analyses were conducted from March 9, 2021, to April 14, 2022.

EXPOSURES: Adolescent-family dyads randomized to the FACE-TC group received 3 weekly 60-minute sessions consisting of the discussion and/or completion of the Lyon Family-Centered Advance Care Planning Survey (session 1), Respecting Choices Next Steps pACP conversation (session 2), and Five Wishes advance directive (session 3). Dyads in the control group received treatment as usual. Both groups received pACP information.

MAIN OUTCOMES AND MEASURES: Congruence was measured by completion of the Statement of Treatment Preferences (a document that discusses 4 hypothetical clinical situations and treatment choices for each scenario: continue all treatments, stop all efforts to keep me alive, or unsure) after session 2 (time 1) and at 3 months (time 2), 6 months (time 3), 12 months (time 4), and 18 months (time 5) after intervention. The influence of FACE-TC on the trajectory of congruence over time was measured by longitudinal latent class analysis.

RESULTS: A total of 252 participants (126 adolescent-family dyads) were randomized. Adolescents (mean [SD] age, 17 [1.9] years) and family members (mean [SD] age, 46 [8.3] years) were predominantly female (72 [57%] and 104 [83%]) and White individuals (100 [79%] and 103 [82%]). There was an 83% (104 of 126) retention at the 18-month assessment. Two latent classes of congruence over time were identified: high-congruence latent class (69 of 116 [60%]) and low-congruence latent class (47 of 116 [41%]). The dyads in the FACE-TC group had a 3-fold odds of being in the high-congruence latent class (odds ratio [OR], 3.22; 95% CI, 1.09-9.57) compared with the control group. Statistically significant differences existed at 12 months (β [SE] = 1.17 [0.55]; P = .03]) but not at 18 months (OR, 2.08; 95% CI, 0.92-4.69). In the high-congruence latent class, good agreement (agreement on 2 or 3 of 4 situations) increased over 12 months. White adolescents and families had significantly greater odds of congruence than a small population of American Indian or Alaska Native, Asian, Black or African American, Hispanic or Latino, or multiracial adolescents and families (OR, 3.97; 95% CI, 1.07-14.69).

CONCLUSIONS AND RELEVANCE: Results of this trial showed that, for those who received the FACE-TC intervention, the families’ knowledge of their adolescents’ end-of-life treatment preferences was sustained for 1 year, suggesting yearly follow-up sessions. Race and ethnicity-based differences in the sustainability of this knowledge reflect a difference in the effect of the intervention and require further study.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02693665.

PMID:35819787 | DOI:10.1001/jamanetworkopen.2022.20696

JAMA Netw Open. 2022 Jul 1;5(7):e2221140. doi: 10.1001/jamanetworkopen.2022.21140.

ABSTRACT

IMPORTANCE: Platform trial design allows the introduction of new interventions after the trial is initiated and offers efficiencies to clinical research. However, limited guidance exists on the economic resources required to establish and maintain platform trials.

OBJECTIVE: To compare cost (US dollars) and time requirements of conducting a platform trial vs a series of conventional (nonplatform) trials using a real-life example.

DESIGN, SETTING, AND PARTICIPANTS: For this economic evaluation, an online survey was administered to a group of international experts (146 participants) with publication records of platform trials to elicit their opinions on cost and time to set up and conduct platform, multigroup, and 2-group trials. Using the reported entry dates of 10 interventions into Systemic Therapy in Advancing Metastatic Prostate Cancer: Evaluation of Drug Efficacy, the longest ongoing platform trial, 3 scenarios were designed involving a single platform trial (scenario 1), 1 multigroup followed by 5 2-group trials (scenario 2), and a series of 10 2-group trials (scenario 3). All scenarios started with 5 interventions, then 5 more interventions were either added to the platform or evaluated independently. Simulations with the survey results as inputs were used to compare the platform vs conventional trial designs. Data were analyzed from July to September 2021.

EXPOSURE: Platform trial design.

MAIN OUTCOMES AND MEASURES: Total trial setup and conduct cost and cumulative duration.

RESULTS: Although setup time and cost requirements of a single trial were highest for the platform trial, cumulative requirements of setting up a series of multiple trials in scenarios 2 and 3 were larger. Compared with the platform trial, there was a median (IQR) increase of 216.7% (202.2%-242.5%) in cumulative setup costs for scenario 2 and 391.1% (365.3%-437.9%) for scenario 3. In terms of total cost, there was a median (IQR) increase of 17.4% (12.1%-22.5%) for scenario 2 and 57.5% (43.1%-69.9%) for scenario 3. There was a median (IQR) increase in cumulative trial duration of 171.1% (158.3%-184.3%) for scenario 2 and 311.9% (282.0%-349.1%) for scenario 3. Cost and time reductions in the platform trial were observed in both the initial and subsequently evaluated interventions.

CONCLUSIONS AND RELEVANCE: Although setting up platform trials can take longer and be costly, the findings of this study suggest that having a single infrastructure can improve efficiencies with respect to costs and efforts.

PMID:35819785 | DOI:10.1001/jamanetworkopen.2022.21140

Ir J Med Sci. 2022 Jul 11. doi: 10.1007/s11845-022-03075-x. Online ahead of print.

ABSTRACT

BACKGROUND: Apatinib, a small molecule targeting VEGFR2, is commonly used for advanced gastric cancer treatment. This prospective cohort study further investigated the efficacy and safety of neoadjuvant apatinib plus chemotherapy in locally advanced gastric carcinoma patients.

METHODS: Ninety-six locally advanced gastric carcinoma patients were divided into the apatinib plus chemotherapy group (N = 45) and chemotherapy group (N = 51) according to their chosen treatment. Apatinib was administered (375 mg/day), and S-1 plus oxaliplatin (SOX) or oxaliplatin plus capecitabine (CapOx) was given as chemotherapy, for 3 cycles with 3 weeks a cycle before surgery.

RESULTS: The objective response rate (62.2% vs. 37.3%, P = 0.015) and pathological response grade (P = 0.011) were better; meanwhile, the tumor-resection rate (95.6% vs. 84.3%, P = 0.143) and pathological complete response rate (23.3% vs. 9.3%, P = 0.080) exhibited increasing trends (without statistical significance) in the apatinib plus chemotherapy group compared with the chemotherapy group. Additionally, the apatinib plus chemotherapy group achieved prolonged disease-free survival (DFS) (P = 0.019) and overall survival (OS) (P = 0.047) compared with the chemotherapy group. After adjusted by multivariate Cox’s regression analysis, neoadjuvant apatinib plus chemotherapy was still superior to chemotherapy regarding DFS (hazard ratio (HR): 0.277, P = 0.014) and OS (HR: 0.316, P = 0.038). Notably, the incidences of adverse events between the two groups were not different (P > 0.050). Moreover, the most common adverse events of neoadjuvant apatinib plus chemotherapy were leukopenia (42.2%), fatigue (37.8%), hypertension (37.8%), and anemia (31.1%).

CONCLUSION: Neoadjuvant apatinib plus chemotherapy realizes better clinical response, pathological response, survival profile, and non-inferior safety profile compared to chemotherapy in locally advanced gastric carcinoma.

PMID:35819743 | DOI:10.1007/s11845-022-03075-x

Oral Radiol. 2022 Jul 11. doi: 10.1007/s11282-022-00637-8. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the crown and root metric properties of two- and single-rooted/multi-canal mandibular canines (MnCn) with single-rooted/single-canal MnCn.

METHODS: Cone-beam computed tomography images of 1000 patients (500 women and 500 men) with both right and left MnCn were analyzed. First, the root and canal morphologies of all teeth were examined. Then, the teeth were divided into three groups; (a) 2-rooted, (b) 1-rooted and multi-canals, (c) 1-rooted and single-canal. Crown lengths/sizes and tooth lengths were compared between the three groups. Statistical analyses were performed using Chi-square, one-way ANOVA, Welch, post hoc pairwise comparison, and independent sample t-tests. The significance level was set at 5%.

RESULTS: Of all the teeth, 2.35% were 2-rooted, and 6.3% were 1-rooted/multi-canal. The frequency of double roots was higher in women (p < 0.05). Double-rooted teeth had longer crown lengths but shorter tooth lengths than single-rooted teeth (p < 0.05). In 2-rooted teeth, buccal and lingual root lengths were similar, root bifurcation levels were mostly at the mid-root, and the mean distance of the bifurcation points of the canals to the cemento-enamel junction was 4.09 mm. Double-rooted teeth were mostly observed unilaterally.

CONCLUSIONS: Since 2-rooted MnCn do not differ significantly from other teeth in terms of crown sizes, it is not possible to differentiate between single- vs. double-rooted MnCn based on clinical examination.

PMID:35819742 | DOI:10.1007/s11282-022-00637-8

Int Ophthalmol. 2022 Jul 12. doi: 10.1007/s10792-022-02402-6. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the effect of intranasal mometasone furoate (INMF) on short-term intraocular pressure (IOP) alterations in children with allergic rhinitis (AR).

METHODS: Children diagnosed with AR and to whom INMF nasal spray had been firstly prescribed were enrolled. Cases with any ocular diseases except for refractive errors were excluded. Complete ophthalmologic examinations including IOP measurements using Tonopen XL were performed before the treatment as well as at the first and sixth weeks of follow-up. Demographics and ophthalmologic findings were noted and statistically analyzed.

RESULTS: Study population consisted of 62 right eyes of 62 children with a mean age of 8.55 ± 3.14 years. Of them, 29 were female (46.8%) and 33 were male (53.2%). Dilated fundoscopy revealed an enlarged Cup/Disc ratio in 12 eyes (19.4%). Family history of glaucoma was positive in 13 cases (21.0%). Mean best corrected visual acuity was found as 0.05 ± 0.08 logMAR. Initial IOP was 17.1 ± 2.3 mmHg; whereas it was measured as 18.2 ± 2.0 mmHg and 17.3 ± 2.1 mmHg at the first and sixth weeks of follow-up, respectively (p < 0.001). Both at the first and sixth weeks of follow-up, significant IOP rise was present in children with a positive family history of glaucoma (p < 0.001 and p = 0.003, respectively). Besides, increased IOP was found in participants with cupping revealed on fundoscopy at the first week of follow-up (p = 0.044).

CONCLUSION: Since children have greater risk for steroid-induced ocular hypertensive response than adults, ophthalmologic evaluation must be recommended in children receiving intranasal steroids.

PMID:35819739 | DOI:10.1007/s10792-022-02402-6

Neurosurg Rev. 2022 Jul 12. doi: 10.1007/s10143-022-01834-z. Online ahead of print.

ABSTRACT

Vestibular schwannoma (VS) is a benign tumor which develops in the internal auditory canal and the cerebellopontine angle, potentially diminishing hearing or balance. Most VS tumors arise from one of two vestibular branches: the superior or inferior vestibular nerve. Determining the specific nerve of origin could improve patient management in terms of preoperative counseling, treatment selection, and surgical decision-making and planning. The aim of this study was to introduce a preoperative testing protocol with high accuracy to determine the nerve branch of origin. The nerve of origin was predicted on the basis of preoperative vestibular evoked myogenic potentials (VEMPs), caloric stimulation test, and pure tone audiometry on 26 recipients. The acquired data were entered into a statistic scoring system developed to allocate the tumor origin. Finally, the nerve of origin was definitively determined intraoperatively. Receiver operating characteristic (ROC) curves analysis of preoperative testing data showed the possibility of predicting the branch of origin. In particular, ROC curve of combined VEMPs absence, nystagmus detectable at caloric stimulation, and PTA < 75 dB HL allowed to obtain high accuracy for inferior vestibular nerve implant of the tumor (area under the curve-AUC = 0.8788, p = 0.012). In 24 of 26 cases, the preoperatively predicted tumor origin was the same as the origin determined during surgery. Preoperative audiological and vestibular evaluation can predict the vestibular tumor branch of origin with high accuracy. Despite the necessity of larger prospective cohort studies, these findings may change preoperative approach, possible functional aspects, and counseling with the patients.

PMID:35819734 | DOI:10.1007/s10143-022-01834-z

J Exp Orthop. 2022 Jul 10;9(1):67. doi: 10.1186/s40634-022-00503-w.

ABSTRACT

PURPOSE: Intraoperative wound irrigation prior to closure during total joint arthroplasty (TJA) is an essential component of preventing infections and limiting health care system costs. While studies have shown the efficacy of dilute betadine in reducing infection risk, there remains concerns over its safety profile and theoretical inactivation by blood and serum. This study aims to compare infection and wound complications between chlorhexidine gluconate (CHG) and betadine lavage during TJA.

METHODS: All primary TJA between 2019-2021 were analyzed at a single institution, and periprosthetic joint infection (PJI), wound drainage, 30 and 90-day emergency room (ER) readmission due to wound complications, aseptic loosening, and revision surgery rate were compared between patients undergoing intraoperative CHG versus betadine lavage prior to closure. Baseline demographics were controlled, and multivariate logistic regression was performed to compare complication rates.

RESULTS: A total of 410 TJA, including 160 hip and 250 knee arthroplasties were included. Compared to the dilute betadine cohort, all TJA patients undergoing CHG lavage had a statistically significant lower 30 and 90-day emergency room readmission rate due to wound complications. Both hip and knee arthroplasty patients with CHG had a statistically significant lower rate of postoperative superficial drainage and dressing saturation at clinic follow-up, but only knee arthroplasty patients had significant decreased readmission rate for incisional wound vacuum placement and close inpatient monitoring of wound healing. Among all TJA, there was no significant association in the rate of PJI requiring return to the OR between groups.

CONCLUSIONS: Although betadine is cost-effective and has been shown to reduce PJI rates, there remains concerns in the literature over soft tissue toxicity and wound healing. This study suggests CHG may be as efficacious as dilute betadine in preventing PJI while also decreasing the risk of superficial drainage and wound complications needing unplanned ER visits during the acute postoperative period.

PMID:35819733 | DOI:10.1186/s40634-022-00503-w