Nevin Manimala

J Neuroimaging. 2022 Sep 18. doi: 10.1111/jon.13051. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Pituitary macroadenomas and meningiomas are common neoplasms arising within the cavernous sinus. Imaging characteristics on MRI can often distinguish these tumors from one another; however, some cases may be more difficult to differentiate. This study compares patterns of cavernous segment internal carotid artery (CS-ICA) stenosis between the two tumor types to establish a novel radiographic method of differentiation.

METHODS: A retrospective analysis of patients with pathology-confirmed meningioma and pituitary adenomas at Tufts Medical Center was performed. The diameter of the CS-ICA at the narrowest point within the cavernous sinus was measured and compared to the ipsilateral petrous segment ICA and contralateral CS-ICA. The mean and range of percent stenosis and frequency of cases of CS-ICA stenosis >15% were determined. Statistical analysis to compare the groups was conducted using the Chi-squared test, Fisher’s exact test, and t-test.

RESULTS: There were a total of 78 out of 231 patients who were included in the study. The mean % ICA stenosis for all meningiomas was 9.3%, with increasing stenosis with increasing World Health Organization grade. Of all meningioma cases, 13 (33%) had greater than 15% ICA stenosis. Mean ICA stenosis for pituitary adenomas was -1.48%. There were no cases of pituitary adenomas causing ICA stenosis >15%.

CONCLUSIONS: Differentiating pituitary adenomas and intracavernous meningioma tumors can have important implications on surgical approach and outcome. Our study found that stenosis of the CS-ICA greater than 15% is highly specific to meningiomas and can serve as a radiologic sign to distinguish between these two tumors.

PMID:36117152 | DOI:10.1111/jon.13051

Dermatol Ther. 2022 Aug 11:e15767. doi: 10.1111/dth.15767. Online ahead of print.

ABSTRACT

Pruritus is a symptom that adversely affects the quality of life of patients with epidermolysis bullosa (EB). Although studies indicate the positive effect of gabapentin on some types of pruritus, its effect on pruritus due to EB remains unexplored. Hence, this study investigated the efficacy of topical gabapentin in treating EB pruritus. We piloted a 6-week, double-blind, split-site, randomized controlled trial on 14 patients with EB pruritus. In each patient, one pruritic lesion received topical gabapentin and the other a placebo. The items of the Leuven Itch Scale were evaluated before and after therapy; the lesions were photographed, and their appearance (i.e., erythema and excoriation severity, pruritic geometric area) was objectively assessed. Statistical analyses were made using SPSS v. 25. Quantitative data were reported as median (interquartile range) or mean ± standard deviation as appropriate. The median age of the 14 patients was 18 years (12-37), and the majority (64.3%) were male. A significant improvement was seen in the geometric area of the pruritic lesion in the intervention group (p = 0.005) but not in the control group (p = 0.054). Erythema severity, excoriation intensity, pruritus frequency and duration, and symptom-related distress significantly improved in both groups (p < 0.05 in all cases), but topical gabapentin failed to offer any statistical superiority relative to the placebo in the between-group analysis (p > 0.05). This study showed no significant difference between topical gabapentin and placebo in erythema severity, excoriation intensity, pruritus frequency and duration, and symptom-related distress among EB patients. However, the lesion area decreased only in the gabapentin group.

PMID:36117146 | DOI:10.1111/dth.15767

Stat Med. 2022 Sep 18. doi: 10.1002/sim.9578. Online ahead of print.

ABSTRACT

Cancer heterogeneity plays an important role in the understanding of tumor etiology, progression, and response to treatment. To accommodate heterogeneity, cancer subgroup analysis has been extensively conducted. However, most of the existing studies share the limitation that they cannot accommodate heavy-tailed or contaminated outcomes and also high dimensional covariates, both of which are not uncommon in biomedical research. In this study, we propose a robust subgroup identification approach based on M-estimators together with concave and pairwise fusion penalties, which advances from existing studies by effectively accommodating high-dimensional data containing some outliers. The penalties are applied on both latent heterogeneity factors and covariates, where the estimation is expected to achieve subgroup identification and variable selection simultaneously, with the number of subgroups being apriori unknown. We innovatively develop an algorithm based on parallel computing strategy, with a significant advantage of capable of processing large-scale data. The convergence property of the proposed algorithm, oracle property of the penalized M-estimators, and selection consistency of the proposed BIC criterion are carefully established. Simulation and analysis of TCGA breast cancer data demonstrate that the proposed approach is promising to efficiently identify underlying subgroups in high-dimensional data.

PMID:36117143 | DOI:10.1002/sim.9578

J Plast Reconstr Aesthet Surg. 2022 Jun 29:S1748-6815(22)00407-7. doi: 10.1016/j.bjps.2022.06.083. Online ahead of print.

ABSTRACT

The thoracodorsal (TD) vessels represent a complex vascular system that offers a variety of pedicled and free flaps. Variations of the classical latissimus dorsi (LD) flap have been developed to overcome its major drawbacks. The thoracodorsal artery perforator (TDAP) flap described by Angrigiani represents one of these options. Other techniques have been defined as “muscle-sparing” latissimus dorsi (MSLD) due to the preservation of the LD muscle and the TD nerve, in whole or in part. Nevertheless, the term “muscle sparing” has also been applied to the descending branch LD (DB-LD) flap which requires the denervation of the LD muscle. According to our knowledge, there are no articles in the literature reviewing and comparing the reconstructive options based on the TD vessels. We performed a systematic search in PubMed, Web of Science, and Cochrane databases to perform a literature review and meta-analysis about the reconstructive options based on the TD vessels. The primary outcome of interest was the percentage of flaps developing a specific early complication, i.e., hematoma of the donor site, seroma of the donor site, partial flap loss, total flap loss, wound dehiscence, and wound infection. Moreover, we analyzed the outcomes and complications of our cases, comparing the MSLD flaps, the DB-LD flaps, and the TDAP flaps. According to both our casuistry and the literature, the three techniques can be considered safe in terms of early donor site complications. According to the literature, MSLD has been shown to develop partial flap necrosis more frequently than the TDAP flap.

PMID:36117135 | DOI:10.1016/j.bjps.2022.06.083

Clin Lung Cancer. 2022 Aug 15:S1525-7304(22)00186-3. doi: 10.1016/j.cllc.2022.08.007. Online ahead of print.

ABSTRACT

BACKGROUND: We investigated the impact of factors that influence TP53 mutations on the efficacy of EGFR-tyrosine kinase inhibitors and potential treatment strategies.

MATERIALS AND METHODS: Tumor samples were collected to screen gene mutations by next-generation sequencing, as well as the patients’ baseline characteristics. The overall response to treatment with TKIs was evaluated based on interval computed tomography scans at each follow-up time point. A Fisher’s exact test and log-rank test were used to determine the statistical differences in this study.

RESULTS: A total of 1134 clinical samples were collected from NSCLC patients, and TP53^mut was identified in 644 cases and EGFR^mut in 622 cases. A low frequency of TP53^mut or more than 50% EGFR co-mutation rate were related to the prognosis of TKI-treated patients. In addition, TP53^mut in the region outside of the DB domain had the strongest correlation with TKI resistance, whereas various types of mutations in the DB domain only had an impact on PFS. A grouping study of EGFR-TKI-based treatment revealed that EGFR-TKIs with chemotherapy were associated with more significant survival benefits for patients with prognostic TP53^mut, whereas EGFR-TKI therapy was favorable for TP53^wt patients. Furthermore, TP53^mut could shorten the time to the relapse of postoperative patients, who will also likely respond well to EGFR-TKIs with chemotherapy.

CONCLUSION: Various characteristics of TP53^mut affect the prognosis of TKI-treated patients to varying degrees. EGFR-TKIs with chemotherapy were benefit for patients’ survival with prognostic TP53^mut, which provides an important reference for treatment management of EGFR^mut patients.

PMID:36117108 | DOI:10.1016/j.cllc.2022.08.007

J Am Pharm Assoc (2003). 2022 Aug 19:S1544-3191(22)00284-9. doi: 10.1016/j.japh.2022.08.014. Online ahead of print.

ABSTRACT

BACKGROUND: The glass ceiling is a metaphor used to describe an invisible barrier that prevents an underrepresented group from rising beyond a certain level. Among pharmacists, underrepresented groups face various barriers and limitations to their successes.

OBJECTIVES: The purpose of this study was to apply the intersectionality framework to data collected from the 2019 National Pharmacist Workforce Study (NPWS) to understand the association of gender and race with leadership aspiration among pharmacists, including differences in perceived barriers and attractors for pursuing leadership.

METHODS: The 2019 NPWS was conducted using an electronic Qualtrics survey. Three e-mails containing the survey link were sent to a systematic random sample of 94,803 pharmacists through the National Association of Boards of Pharmacy Foundation e-profile system. The 2019 NPWS had an overall response rate of 6% (5705/94,803). A total of 8466 pharmacists clicked on the survey link, resulting in a usable response rate of 67.3% (5705/8466). Data were analyzed in SPSS software using descriptive and Pearson’s r and chi-square test statistics.

RESULTS: Black, Indigenous, and People of Color (BIPOC) pharmacists reported holding 10.7% of all leadership positions. Leadership positions included manager, assistant manager, executive, dean, director, chief pharmacy officer, owner or partner, and other leadership position types. White men and women reported the lowest interest in leadership (38.8% and 37.7%), whereas Black men (65.1%), Latinas (59.2%), Black women (58.5%), and Latinos (57.1%) had the highest interest in leadership. “The ability to make an impact” was the most frequently selected attractor for wanting to pursue leadership, selected by 92.5% and 79.6% of Black men and women, respectively, 77.8% of Other women, and 76.9% of Latinos. At graduation from pharmacy school, the student debt loan average of all graduation years ranged from $63,886 (± $73,701) for Other men to $112,384 (± $105,417) for Black women. Higher student loan debt was positively correlated with wanting to pursue a leadership position (r = 0.22, P < 0.001). Black women graduating 2011-2019 had the highest student loan debt at graduation ($194,456 ± $88,898).

CONCLUSION: Interest in leadership positions by BIPOC pharmacists compared with reported leadership roles were inversely correlated. Understanding the discrepancy in interest in leadership and reported leadership positions held, particularly with relation to race and gender, is essential to understanding equity in pharmacy leadership. Further research is warranted to understand the factors that impede the ascension of women and underrepresented pharmacists into leadership positions.

PMID:36117106 | DOI:10.1016/j.japh.2022.08.014

Clin Colorectal Cancer. 2022 Aug 12:S1533-0028(22)00073-1. doi: 10.1016/j.clcc.2022.08.002. Online ahead of print.

ABSTRACT

BACKGROUND: The real-world survival benefit of FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus anti-VEGF therapy (Triplet) over doublet chemotherapy (Doublet) remains controversial in patients with BRAF^V600E mutant metastatic colorectal cancer (mCRC).

PATIENTS AND METHODS: WJOG13219G was a multicenter, retrospective, registry-based study of patients with BRAF^V600E mutant mCRC who received first-line triplet or doublet chemotherapy from January 2014 to December 2019 in Japan. Inverse probability of treatment weighting (IPTW) was used to adjust for patient background.

RESULTS: The analysis included 79 and 91 patients in the Triplet and Doublet groups, respectively. The Triplet group was significantly younger and had better performance status. No statistical difference was noted in progression-free survival (PFS; HR, 0.82; 95% CI, 0.60-1.13; P = .22) and overall survival (OS; HR, 0.88; 95% CI, 0.62-1.25; P = .48) between both groups. IPTW analysis also showed no difference between the 2 groups in PFS (HR, 0.86; 95% CI, 0.69-1.08; P = .20) and OS (HR, 0.93; 95% CI, 0.73-1.20; P = .59). The Triplet and Doublet groups had an objective response rate of 53% and 41%, respectively (P = .10). At least one grade 3 or 4 adverse event was seen in 51 (65%) and 43 (47%) patients in the Triplet and Doublet groups, respectively, with the incidence of neutropenia being significantly higher in the former.

CONCLUSION: Triplet therapy had no survival benefit versus doublet therapy in the overall and IPTW cohorts or specific subgroups for real-world patients with BRAF^V600E mutant mCRC.

PMID:36117091 | DOI:10.1016/j.clcc.2022.08.002

Schizophr Res. 2022 Sep 15:S0920-9964(22)00363-2. doi: 10.1016/j.schres.2022.09.021. Online ahead of print.

ABSTRACT

Catatonia is a neuropsychiatric disorder characterised by altered movement, speech, and behaviour. Clozapine is an established therapy for treatment-resistant schizophrenia, but its role in catatonia has not been systematically examined. In this systematic review, we aimed to assess the evidence for clozapine as a treatment for catatonia. Full text original research articles in English where at least one patient with catatonia was treated with clozapine were included, provided catatonia did not occur solely in the context of neuroleptic malignant syndrome. Results were tabulated with calculations of summary statistics presented. Risk of bias was assessed with the Tool for Evaluating the Methodological Quality of Case Reports and Case Series. 182 patients were included, 81 from cohort studies and 101 from case reports or case series. 119/182 patients (65 %) had a specified underlying diagnosis of schizophrenia. Over 80 % of reported patients with catatonia had at least partial remission following treatment with clozapine across both cohort studies and case reports and case series. Among the case reports and series, 24/101 patients (23.8 %) followed clozapine withdrawal. Overall, 25 studies were of low quality, 60 of moderate quality and 8 of high quality. Our findings should be interpreted with caution, as the reliance on case reports, case series and small cohort studies is susceptible to reporting biases, regression to the mean and confounding by other treatments. Future research could use large healthcare databases to ascertain outcomes in those on clozapine with a history of catatonia given the difficulty and expense of conducting randomised controlled trials.

PMID:36117082 | DOI:10.1016/j.schres.2022.09.021

J Pediatr Health Care. 2022 Sep 15:S0891-5245(22)00238-3. doi: 10.1016/j.pedhc.2022.08.005. Online ahead of print.

ABSTRACT

This survey aimed to evaluate contemporary pediatric nurse practitioner (PNP) practice as it relates to the competencies of both the primary and acute care population focus and settings of practice to guide curriculum revisions. The design of the study was a cross-sectional survey of PNPs certified by the Pediatric Nursing Certification Board. There were 2,265 surveys completed. Regardless of the certification type, PNPs report providing care across settings and integrating the competencies of both the primary and acute care PNP into practice. This warrants further consideration by programs to prepare future PNPs for dual primary and acute care certification.

PMID:36117073 | DOI:10.1016/j.pedhc.2022.08.005

J Heart Lung Transplant. 2022 Aug 15:S1053-2498(22)02071-X. doi: 10.1016/j.healun.2022.08.006. Online ahead of print.

ABSTRACT

BACKGROUND: Risk scores integrate clinical variables emphasizing symptoms, exercise capacity, and measures of cardiac strain to predict clinical outcome better than any single value in pulmonary arterial hypertension (PAH). Risk scores have demonstrated prognostic utility for outcomes in registries, and recent studies have suggested that they are also therapy-responsive in controlled trials.

METHODS: FREEDOM-EV, a global, placebo-controlled, event-driven study, randomized 690 PAH participants 1:1 to oral treprostinil (TRE) or placebo. Clinical assessments were performed every 12 weeks to calculate the non-invasive French risk assessment (FRA), 4-strata COMPERA, REVEAL 2.0, and REVEAL Lite 2; median follow-up was 58 weeks. The Week 12 risk scores were used to predict time to clinical worsening (from Week 12) with Kaplan-Meier product-limit estimates. Log-rank test was used to calculate the statistical difference among risk categories, and mediation analysis tested the hypothesis that improvements in risk score contributed to reduced likelihood for clinical worsening. We assessed the previously proposed “net clinical benefit” (achievement of FRA low-risk status and absence of clinical worsening).

RESULTS: Both REVEAL scores, COMPERA, and FRA at Week 12 predicted subsequent clinical worsening better than baseline risk. Mediation analysis demonstrated that Week 12 risk score reduction explained part of TRE’s effect on clinical worsening, especially for those with higher baseline risk. TRE assigned participants were more likely to achieve the previously proposed “net clinical benefit” at Weeks 24 and beyond. Few participants who achieved ‘net clinical benefit’ had subsequent clinical worsening.

CONCLUSIONS: Contemporary risk scores were therapy responsive in FREEDOM-EV and early improvements predicted subsequent outcomes. This post hoc analysis suggests that risk scores may be a surrogate for clinical worsening.

PMID:36117055 | DOI:10.1016/j.healun.2022.08.006