Nevin Manimala

Exp Dermatol. 2023 Oct 21. doi: 10.1111/exd.14963. Online ahead of print.

ABSTRACT

In the registration trial of risankizumab for patients with moderate-to-severe psoriasis in Japan, similar Psoriasis Area Severity Index (PASI) responses were observed for 75 mg or 150 mg risankizumab at most time points up to 52 weeks, except for PASI 100 at week 16. The use of 75 mg risankizumab offers an attractive option considering the high cost of risankizumab. However, it is unknown whether patients with mild-to-moderate psoriasis respond similarly, and the efficacy data of non-Japanese patients is also lacking. We retrospectively included 30 consecutive Chinese patients receiving half-dose (75 mg) risankizumab as scheduled up to 52 weeks. Compared with biologic-experienced group, biologic-naive group had a significantly higher PASI 50/75/90/100 achievement (p = 0.0098/0.0039/0.0016/0.0054) at week 52. PASI 50/75/90/100 curves in biologic-naive group (p = 0.0117/0.0239/0.0143/0.0269) were also significantly higher when analysed generalized estimating equations (GEE) model. Though there was no statistically significant difference in terms of PASI 50/75/90/100 responses at any time points between those with body weight ≦ 65 kg and those >65 kg, a tendency of secondary failure was noted in those >65 kg from week 40 onwards. Patients who were both biologic-naive and weighed ≦ 65 kg achieved sustained PASI 50/75/90 responses from week 16/28/40 onwards, respectively, indicating that they could be considered as potential candidates for 75 mg risankizumab. Though PASI 75 curve in patients without diabetes mellitus (DM) surpassed that in patient without DM, curves of other parameters did not reach significance when analysed by GEE model. There was no HBV, HCV or TB reactivation, nor other new safety signals during the 52-week observational period. Providing risankizumab with flexible dosing options is beneficial in clinical practice considering the high cost of this medication.

PMID:37864438 | DOI:10.1111/exd.14963

Anaesthesia. 2023 Oct 21. doi: 10.1111/anae.16148. Online ahead of print.

ABSTRACT

Acute postoperative pain remains a critical treatment priority and has prompted a search for technologies and techniques to assist with intra-operative analgesic monitoring and management. Anaesthetists traditionally rely on clinical judgement to guide intra-operative analgesia, but several emerging technologies such as the nociception level index herald the possibility of routine intra-operative analgesia monitoring. However, the impact of devices like nociception level index on postoperative outcomes has not been proven. We undertook a systematic review and meta-analysis of articles which compared nociception level index-guided analgesia to standard care. The primary outcomes were pain intensity and opioid consumption during the first 60-120 min after surgery. Secondary outcomes were the incidence of postoperative nausea and vomiting and duration of stay in the post-anaesthesia care unit. Ten studies, collectively including 662 patients and published between 2019 and 2023, met inclusion criteria for both the qualitative systematic review and quantitative meta-analysis. Risk of methodological bias was generally low or unclear, and six studies reported a significant conflict of interest relevant to their findings. Our meta-analysis was performed using a random-effects model. It found statistically significant benefits of nociception level index-guided analgesia for early postoperative pain (mean (95%CI) difference -0.46 (-0.88 to -0.03) on an 11-point scale, p = 0.03), and opioid requirement (mean (95%CI) difference -1.04 (-1.94 to -0.15) mg intravenous morphine equivalent, p = 0.02). Our meta-analysis of the current literature finds that nociception level index-guided analgesia statistically significantly reduces reported postoperative pain intensity and opioid consumption but fails to show clinically relevant outcomes. We found no evidence that nociception level index-guided analgesia affected postoperative nausea and vomiting nor duration of stay in the post-anaesthesia care unit.

PMID:37864430 | DOI:10.1111/anae.16148

J Magn Reson Imaging. 2023 Oct 21. doi: 10.1002/jmri.29044. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) results in right ventricular (RV) dysfunction, subsequently leading to left ventricular (LV) impairment. The mechanism underlying ventricular interdependence is largely uninvestigated.

PURPOSE: To explore the biventricular dysfunction and the ventricular interdependence in PH patients.

STUDY TYPE: Retrospective.

POPULATION: One hundred and seven PH patients (mean pulmonary artery pressure >20 mmHg) and 72 age- and sex-matched controls with cardiac magnetic resonance imaging (MRI) studies.

FIELD STRENGTH/SEQUENCE: 3.0 T/balanced steady-state free precession sequence.

ASSESSMENT: LV and RV ejection fractions (EF) and RV and LV radial, circumferential, and longitudinal strains were assessed using commercial software. Strains were compared between controls, PH patients with preserved RVEF (RVEF ≥40%, N = 48), and PH patients with reduced RVEF (RVEF <40%, N = 59).

STATISTICAL TESTS: Chi-squared tests or Fisher’s exact test, t tests or Mann-Whitney U test, one-way ANOVA with Bonferroni’s post hoc correction or Kruskal-Wallis test, Pearson or Spearman correlation, and multivariable linear regression analysis. A two-tailed P < 0.05 was deemed statistically significant.

RESULTS: RV strain decreased sequentially from controls, through PH with preserved RVEF, to PH with reduced RVEF. PH patients with reduced RVEF had significantly lower LV strain, especially septal strain, and LV peak diastolic strain rate compared with both controls and PH patients with preserved RVEF. Multivariable analyses showed that RVEF was independently correlated with LV strain; furthermore, independent of RVEF, RV strain was significantly correlated with LV strain (LVGRS: β = 0.416; LVGCS: β = -0.371; LVGLS: β = 0.283).

DATA CONCLUSION: Subclinical impairment of RV function was found in PH with preserved RVEF. LV strain was impaired when RV was dysfunctional, which was associated with worsening RV strain. Therefore, while focusing on improving RV function, LV dysfunction in PH patients should also be monitored and treated early in order to slow the progression of the disease.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

PMID:37864419 | DOI:10.1002/jmri.29044

Rhinology. 2023 Oct 21. doi: 10.4193/Rhin23.160. Online ahead of print.

ABSTRACT

BACKGROUND: Inhibitors of apoptosis proteins (IAPs) modulate the inflammatory process, and may facilitate the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to observe if IAPs were differently expressed between patients with CRSwNP and controls, and to correlate the expression of IAPs with some inflammatory markers, as with the response to nasal corticosteroids in patients with CRSwNP.

METHODOLOGY: We obtained nasal biopsies from patients with CRSwNP (n=27) and controls (n=16). qRT-PCR measured the expression of IAPs and caspases, while Luminex assay measured the concentration of cytokines. Unpaired parametric tests and Principal Component Analysis (PCA) were used for statistical analysis.

RESULTS: We observed lower expression of IAP genes (XIAP, BIRC2/IAP1, and BIRC3/IAP2) in CRSwNP patients compared to controls, and we identified that patients with bad response to corticosteroids presented lower levels of BIRC2/IAP1, XIAP, BCL2, CASP9, and IL-17, and higher levels of CASP7 and TGF-β.

CONCLUSIONS: IAPs expression was downregulated in CRSwNP, and was associated with poorer response to nasal corticosteroids. The present findings suggest the importance of IAPs as a link between environment and the host inflammatory responses, and this pathway could be explored as a potential new target therapy for patients with CRSwNP.

PMID:37864409 | DOI:10.4193/Rhin23.160

Trop Med Int Health. 2023 Oct 21. doi: 10.1111/tmi.13940. Online ahead of print.

ABSTRACT

OBJECTIVE: The primary objective of this study was to ascertain the acceptance, initiation, implementation and treatment completion rates of tuberculosis (TB) preventive therapy (TPT) using 3HP (INH-Rifapentine) among household contacts of microbiologically confirmed drug sensitive TB cases on anti-tubercular treatment under programmatic real-world settings. The secondary objectives were to estimate the prevalence and predictors of latent TB infection (LTBI) in household contacts of the index TB cases. We also ascertained the safety profile of the 3HP TPT regimen in the household contacts.

METHODS: This prospective observational study was conducted at 10 TB chest clinics in Delhi, India during 2022-2023. Household contacts aged 14 and older who tested positive for TB infection on a Tuberculin Skin test were initiated on the 3HP regimen. Logistic regression was performed by including statistically significant independent variables in multiple prediction models. p < 0.05 was considered statistically significant. STATA, version 15.1, was used to compute all analyses.

RESULTS: A total of 1067 (84.68%) eligible contacts of microbiologically confirmed, drug sensitive TB cases underwent screening with tuberculin skin test (TST), 614 (95.6%) LTBI positive contacts accepted the initiation of TPT, and 564 (91.8%) of those initiated on TPT completed the treatment. The major reason for refusal of screening was the lack of perception of risk of TB disease due to asymptomatic status. The prevalence of LTBI positivity through TST was 61.5% (95% CI, 58.5%, 64.4%). Adverse events were reported by 195 (31.8%) contacts initiated on 3HP of which 20 participants discontinued TPT. None of the sociodemographic factors showed a significant association with LTBI positivity (except age) or TPT completion rates.

CONCLUSION: LTBI management with 3HP is feasible among adolescent and adult household contacts in India with high rates of adherence from initiation until treatment completion. The maximum attrition of participants occurred at the time of screening for LTBI using TST.

PMID:37864386 | DOI:10.1111/tmi.13940

Pediatr Dermatol. 2023 Oct 20. doi: 10.1111/pde.15459. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVE: Stiff skin syndrome (SSS) is a rare disorder characterized by “rock hard” indurated skin affecting different body parts. The localized variant poses a diagnostic challenge, as it is frequently mistaken for other inflammatory connective tissue disorders. The aim of this study is to provide insightful clinical, radiologic and diagnostic data that might prove useful for the evaluation, management and treatment of pediatric patients with segmental SS.

METHODS: This single-center cohort study included patients ≤18 years diagnosed with localized SSS from 1988 to 2021 in a quaternary pediatric healthcare center in Toronto, Canada. Data included demographics, clinical, histopathologic and radiologic features, treatments, and clinical course. Data were summarized with descriptive statistics (mean, standard deviation, medians, interquartile ranges [IQRs]) and frequencies.

RESULTS: A total of 11 patients were included. The sclerotic changes were measured clinically and radiologically, by a total of 16 imaging studies: 13 magnetic resonance imaging (MRI) and 3 ultrasound. MRI readings showed abnormal high signal intensity of the affected tissue correlating with the anatomical site of involvement in all cases, specifically, in the shoulder/pelvic girdle with limb extension. Shear wave ultrasound elastography (SWE) demonstrated higher values within the dermis compared to the control site.

CONCLUSION: The presence of segmental sclerotic changes that affects the pelvic/shoulder girdle with extension to the extremities, in the absence of inflammation on biopsy and abnormal signaling intensity on imaging is suggestive of SSS. Skin SWE is a feasible, noninvasive, and objective instrument to evaluate and monitor sclerotic changes overtime, it could be potentially extrapolated to other pediatric skin sclerotic conditions.

PMID:37864376 | DOI:10.1111/pde.15459

Eur J Oral Sci. 2023 Oct 20:e12959. doi: 10.1111/eos.12959. Online ahead of print.

ABSTRACT

The present study aimed to compare the microstructure, physical, and mechanical properties of three commercially available dental polychromatic multilayer zirconia materials of uniform composition: Dima Mill Zirconia ML, VITA YZ/ST Multicolor, and VITA YZ/XT Multicolor (with 3, 4, and 5 mol% Y₂ O₃ , respectively); thus, the influence of Y₂ O₃ content on the above properties of the produced materials was experimentally studied. Homogeneous zirconia ceramics with a dense micro- and nanostructure, without pores or defects, were produced after milling the blocks and sintering, which resulted in yttrium-stabilized tetragonal and cubic zirconia. Statistical analysis of the results of measurable magnitudes was performed by the one-way ANOVA test. The increase of Y₂ O₃ content (from 3 to 5 mol%) favored larger grain and crystallite sizes and a decrease of the values of the mechanical properties; yet, the differences were statistically insignificant. Clinically, these differences are expected to have no impact on their function in the oral cavity, both in terms of their fracture propensity and the damage that can be caused to the opposing teeth. Accordingly, the experimental results qualify the polychromic multilayer zirconia ceramics of uniform composition fabricated by milling technology for use in dental restorations.

PMID:37864371 | DOI:10.1111/eos.12959

J Magn Reson Imaging. 2023 Oct 21. doi: 10.1002/jmri.29072. Online ahead of print.

ABSTRACT

BACKGROUND: Deep-learning is widely used for lesion classification. However, in the clinic patient data often has missing images.

PURPOSE: To evaluate the use of generated, duplicate and empty(black) images for replacing missing MRI data in AI brain tumor classification tasks.

STUDY TYPE: Retrospective.

POPULATION: 224 patients (local-dataset; low-grade-glioma (LGG) = 37, high-grade-glioma (HGG) = 187) and 335 patients (public-dataset (BraTS); LGG = 76, HGG = 259). The local-dataset was divided into training (64), validation (16), and internal-test-data (20), while the public-dataset was an independent test-set.

FIELD STRENGTH/SEQUENCE: T1WI, T1WI+C, T2WI, and FLAIR images (1.5T/3.0T-MR), obtained from different suppliers.

ASSESSMENT: Three image-to-image translation generative-adversarial-network (Pix2Pix-GAN) models were trained on the local-dataset, to generate T1WI, T2WI, and FLAIR images. The rating-and-preference-judgment assessment was performed by three human-readers (radiologist (MD) and two MRI-technicians). Resnet152 was used for classification, and inference was performed on both datasets, with baseline input, and with missing data replaced by 1) generated images; 2) duplication of existing images; and 3) black images.

STATISTICAL TESTS: The similarity between the generated and the original images was evaluated using the peak-signal-to-noise-ratio (PSNR) and the structural-similarity-index-measure (SSIM). Classification results were evaluated using accuracy, F1-score and the Kolmogorov-Smirnov test and distance.

RESULTS: For baseline-state, the classification model reached to accuracy = 0.93,0.82 on the local and public-datasets. For the missing-data methods, high similarity was obtained between the generated and the original images with mean PSNR = 35.65,32.94 and SSIM = 0.87,0.91 on the local and public-datasets; 39% of the generated-images were labeled as real images by the human-readers. The classification model using generated-images to replace missing images produced the highest results with mean accuracy = 0.91,0.82 compared to 0.85,0.79 for duplicated and 0.77,0.68 for use of black images; DATA CONCLUSION: The feasibility for inference classification model on an MRI dataset with missing images using the Pix2pix-GAN generated images, was shown. The stability and generalization ability of the model was demonstrated by producing consistent results on two independent datasets.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 5.

PMID:37864370 | DOI:10.1002/jmri.29072

Ear Nose Throat J. 2023 Oct 20:1455613231205991. doi: 10.1177/01455613231205991. Online ahead of print.

ABSTRACT

Background: The association between increased nasal resistance (NR) and obstructive sleep apnea syndrome (OSAS) is controversial. The purpose of this study was to examine nasal ventilation function (NVF) in children with OSAS, with a focus on its pathogenetic role. Methods: Children were recruited and divided into the OSAS group (n = 109) and control group (n = 116). The participants underwent polysomnography (PSG), measurement of NR, and acoustic rhinometry (AR). A combination of intranasal corticosteroids (ICS) and oral montelukast (OM) was administered to 90 children with mild to moderate OSAS for 12 weeks. After excluding participants who dropped out or were lost to follow-up, there were 58 children who responded to the treatment, who were divided into 2 groups-A and B. We compared the size of the tonsil adenoids, the PSG, NR, and AR before and after treatment in the 2 groups. Results: Children aged 6 to 12 years with OSAS had significantly higher NR than the control group (P < .05). The OSAS group had a smaller nasal minimal cross-sectional area (NMCA), nasal cavity volume (NCV) from 0 to 5 cm, and nasopharyngeal volume (NPV) from 6 to 8 cm than the control group, and the difference was statistically significant (P < .05 or P < .01). A total of 58 (84.1%) children responded to the 12-week ICS+OM treatment and 11 (15.9%) children did not respond to the treatment. Effective treatment was achieved in 32 children, as evidenced by a significant reduction in tonsil adenoid size and variations in NR and AR values. There were significant improvements in NR, NMCA, and NCV in the remaining 26 children who were successfully treated, but there was no change in tonsil adenoids and NPV value. Conclusion: NVF may play an important pathogenetic role in children with OSAS.

PMID:37864363 | DOI:10.1177/01455613231205991

J Pharm Pract. 2023 Oct 20:8971900231200900. doi: 10.1177/08971900231200900. Online ahead of print.

ABSTRACT

Background: The optimal method for implementing rapid diagnostic testing (RDT) into clinical practice has not been determined for gram-negative rod (GNR) bacteremia. At our institution, RDT was implemented in conjunction with real-time notification of results to decentralized clinical pharmacists. Objective: To determine the impact of RDT result notification plus real-time clinical pharmacist review on the management of GNR bacteremia. Methods: This retrospective, matched cohort study included patients with a positive blood culture for a GNR on the BIOFIRE® Blood Culture Identification 2 panel from September 2020 to August 2021 (historical) and October 2021 to September 2022 (interventional). Exclusion criteria were polymicrobial bacteremia, discrepant RDT results from traditional culture, 24-hour mortality, and comfort care or not admitted at the time of RDT result. Patients were matched based on age, pathogen, and resistance. The primary endpoint was time from Gram stain to appropriate antibiotic therapy. Results: This study consisted of 240 patients (n = 120 historical, n = 120 interventional). Escherichia coli was isolated in 71% of patients with extended-spectrum beta-lactamase-producing organisms isolated in 8%. There was no difference in median time to appropriate therapy (0 vs 0 hours, P = 0.28). There was a statistically significant decrease in time to first organism-directed change in therapy (40 vs 11 hours; P < 0.01). Length of stay, days of anti-pseudomonal therapy, and inpatient mortality did not differ between groups. Conclusion: Implementation of RDT plus real-time clinical pharmacist review did not significantly decrease time to appropriate therapy in patients with GNR bacteremia but significantly reduced time to organism-directed antibiotic changes.

PMID:37864345 | DOI:10.1177/08971900231200900