Nevin Manimala

Cancer Med. 2023 Jun 3. doi: 10.1002/cam4.6207. Online ahead of print.

ABSTRACT

BACKGROUND: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology.

MATERIALS & METHODS: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

RESULTS: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use.

CONCLUSION: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.

PMID:37269199 | DOI:10.1002/cam4.6207

Cancer Med. 2023 Jun 3. doi: 10.1002/cam4.6184. Online ahead of print.

ABSTRACT

BACKGROUND: Dacomitinib significantly improves progression-free survival and overall survival (OS) compared with gefitinib in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-activating mutations. However, dacomitinib often causes skin toxicities, resulting in treatment discontinuation. We aimed to evaluate a prophylactic strategy for skin toxicity induced by dacomitinib.

METHODS: We performed a single-arm, prospective, open-label, multi-institutional phase II trial for comprehensive skin toxicity prophylaxis. Patients with NSCLC harboring EGFR-activating mutations were enrolled and received dacomitinib with comprehensive prophylaxis. The primary endpoint was the incidence of skin toxicity (Grade ≥2) in the initial 8 weeks.

RESULTS: In total, 41 Japanese patients participated between May 2019 and April 2021 from 14 institutions (median age 70 years; range: 32-83 years), 20 were male, and 36 had a performance status of 0-1. Nineteen patients had exon 19 deletions and L858R mutation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration. Skin toxicities (Grade ≥2) occurred in 43.9% of patients (90% confidence interval [CI], 31.2%-56.7%). The most frequent skin toxicity was acneiform rash in 11 patients (26.8%), followed by paronychia in five patients (12.2%). Due to skin toxicities, eight patients (19.5%) received reduced doses of dacomitinib. The median progression-free survival was 6.8 months (95% CI, 4.0-8.6 months) and median OS was 21.6 months (95% CI, 17.0 months-not reached).

CONCLUSION: Although the prophylactic strategy was ineffective, the adherence to prophylactic medication was quite good. Patient education regarding prophylaxis is important and can lead to improved treatment continuity.

PMID:37269194 | DOI:10.1002/cam4.6184

Cancer Med. 2023 Jun 3. doi: 10.1002/cam4.6187. Online ahead of print.

ABSTRACT

BACKGROUND: In randomized trials in women with breast cancer, exercise has been shown to have beneficial effects on cancer-related circulating biomarkers that may impact survival. Such studies are lacking for ovarian cancer.

METHODS: This secondary analysis of a published randomized controlled trial examined the impact of a 6-month exercise intervention versus attention-control on change in prespecified circulating biomarkers (cancer antigen 125 (CA-125), C-reactive protein (CRP), insulin-like growth factor-1(IGF-1), insulin and leptin) in a subset of participants who provided a fasting blood draw (N = 104/144) at enrollment and at 6 months. Change in biomarkers between study arms was compared using a linear mixed effects model analysis. An exploratory analysis of the exercise intervention versus attention-control on all-cause mortality included all (N = 144) participants. All statistical tests were two-sided.

RESULTS: Participants included in the biomarker analysis were 57.0 ± 8.8 (mean ± SD) years old and 1.6 ± 0.9 years post-diagnosis. Adherence to the exercise intervention was 176.4 ± 63.5 min/week. Post intervention IGF-1 (group difference in change: -14.2 (-26.1 to -2.3) ng/mL (least squared means (95% CI))) and leptin (-8.9 (-16.5 to -1.4) ng/mL) were significantly reduced in the exercise group (N = 53) compared to those in attention-control (N = 51). No group difference in change was seen for CA-125 (p = 0.54), CRP (p = 0.95), or insulin (p = 0.37). With median follow-up of 70 months [range 6.6-105.4 months], 50/144 (34.7%) (exercise group; 24/74 (32.4%) versus attention-control group; 26/70 (37.1%)) participants died with no between group difference in overall survival (p = 0.99).

CONCLUSIONS: Further studies are needed to determine the clinical significance of exercise-induced changes in cancer-related circulating biomarkers in women with ovarian cancer.

PMID:37269192 | DOI:10.1002/cam4.6187

Congenit Anom (Kyoto). 2023 Jun 3. doi: 10.1111/cga.12527. Online ahead of print.

ABSTRACT

Cleft lip and/or palate anomalies (CL ± P) are the most frequent birth defects affecting the orofacial region in humans. Although their etiology remains unclear, the involvement of environmental and genetic risk factors is known. This observational study aimed to investigate how the use of crude drugs with estrogen activity influenced an animal model’s ability to prevent CL ± P. A/J mice were randomly divided into six experimental groups. Five of these groups consumed a drink containing crude drug licorice root extract, with the following weights attributed to each group: 3 g in group I, 6 g in group II, 7.5 g in group III, 9 g in group IV, and 12 g in group V, whereas a control group consumed tap water. The effect of licorice extract was examined for fetal mortality and fetal orofacial cleft development compared to the control group. The rates for fetal mortality were 11.28%, 7.41%, 9.18%, 4.94%, and 7.90% in groups I, II, III, IV, and V, respectively, compared to 13.51% in the control group. There were no significant differences in the mean weight of alive fetuses in all five groups compared to the control group (0.63 ± 0.12). Group IV showed the lowest orafacial cleft occurrence of 3.20% (8 fetuses) with statistical significance (p = 0.0048) out of 268 live fetuses, whereas the control group had the occurrence of 8.75% (42 fetuses) among 480 live fetuses. Our study showed that the dried licorice root extract may reduce orofacial birth defects in experimental animal studies.

PMID:37269175 | DOI:10.1111/cga.12527

Med Decis Making. 2023 Jun 2:272989X231171166. doi: 10.1177/0272989X231171166. Online ahead of print.

ABSTRACT

The unit normal loss integral (UNLI) is widely used in decision analysis and risk modeling, including in the computation of various value-of-information metrics, but its closed-form solution is only applicable to comparisons of 2 strategies.We derive a closed-form solution for 2-dimensional UNLI, extending the applicability of the UNLI to 3-strategy comparisons.Such closed-form computation takes only a fraction of a second and is free from simulation errors that affect the hitherto available methods.In addition to the relevance in 3-strategy model-based and data-driven decision analyses, a particular application is in risk prediction modeling, where the net benefit of a classifier should always be compared with 2 default strategies of treating none and treating all.

PMID:37269136 | DOI:10.1177/0272989X231171166

Foot Ankle Int. 2023 Jun 2:10711007231174198. doi: 10.1177/10711007231174198. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study was to validate the Foot and Ankle Outcome Score (FAOS) for osteochondral lesions of the talus (OLTs). We hypothesize that the FAOS will meet all 4 psychometric criteria for validity in this patient population.

METHODS: From 2008 to 2014, a total of 208 patients with OLTs were included in the construct validity portion of the study. All patients completed FAOS and 12-Item Short-Form Health Survey (SF-12) scores. Twenty additional patients were prospectively recruited and were asked to complete questionnaires to determine the relevance of each of the FAOS questions as it related to their OLT. Forty-four patients completed the FAOS 1 month after the first FAOS to assess reliability via Spearman correlation coefficient. Responsiveness of the FAOS was assessed with 54 patients who had both preoperative and postoperative FAOS scores via Student paired t test with significance determined as P < .05. In total, 229 unique patients were included in this study.

RESULTS: Statistically significant associations were found between all FAOS and SF-12 subscales (P < .01). The FAOS symptoms subscale demonstrated the lowest correlation with the SF-12 physical health domains. No floor or ceiling effects were identified. Weak correlations were calculated between the 5 FAOS subscales and the SF-12 mental component summary score. All FAOS domains met the threshold for acceptable content validity (score > 2.0). All FAOS subscales demonstrated acceptable test-retest reliability, with ICC values ranging from 0.81 (ADL) to 0.92 (Pain).

CONCLUSION: This study demonstrates the acceptable yet moderate construct and content validity, reliability, and responsiveness of the FAOS for patients with OLTs of the ankle joint. We endorse the use of the FAOS in evaluating ankle OLTs in both the research and clinical setting and consider it a useful patient-reported, self-administered instrument following surgical intervention.

LEVEL OF EVIDENCE: Level IV, retrospective case study.

PMID:37269134 | DOI:10.1177/10711007231174198

Neurorehabil Neural Repair. 2023 Jun 2:15459683231177598. doi: 10.1177/15459683231177598. Online ahead of print.

ABSTRACT

Baseline scores after stroke have long been known as a good predictor of post-stroke outcomes. Similarly, the extent of baseline impairment has been shown to strongly correlate with spontaneous recovery in the first 3 to 6 months after stroke, a principle known as proportional recovery. However, recent critiques have proposed that proportional recovery is confounded, most notably by mathematical coupling and ceiling effects, and that it may not be a valid model for post-stroke recovery. This article reviews the current understanding of proportional recovery after stroke, discusses its supposed confounds of mathematical coupling and ceiling effects, and comments on the validity and usefulness of proportional recovery as a model for post-stroke recovery. We demonstrate that mathematical coupling of the true measurement value is not a real statistical confound, but rather a notational construct that has no effect on the correlation itself. On the other hand, mathematical coupling does apply to the measurement error and can spuriously amplify correlation effect sizes, but should be negligible in most cases. We also explain that compression toward ceiling and the corresponding proportional recovery relationship are consistent with our understanding of post-stroke recovery dynamics, rather than being unwanted confounds. However, while proportional recovery is valid, it is not particularly groundbreaking or meaningful as previously thought, just like how correlations between baseline scores and outcomes are relatively common in stroke research. Whether through proportional recovery or baseline-outcome regression, baseline scores are a starting point for investigating factors that determine recovery and outcomes after stroke.

PMID:37269116 | DOI:10.1177/15459683231177598

J Orthod. 2023 Jun 2:14653125231176575. doi: 10.1177/14653125231176575. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine differences in the location of centre of resistance (Cres) between functional and hypofunctional teeth and to evaluate the relationship between the pulp cavity volume and locations of the Cres, using the finite element (FE) method.

DESIGN: Retrospective cohort study.

PARTICIPANTS: FE models of right maxillary central incisor, derived from cone-beam computed tomography (CBCT) images of 46 participants, were divided into normal function (n = 23) and hypofunction (n = 23) groups using anterior overbite and cephalometric measurements.

METHODS: Measurements of the tooth and pulp cavity volume were made from CBCT. Cres levels were presented as percentages of the root length from the root’s apex. All data were analysed and compared using the independent t-test (P < 0.05). The relationship between the location of Cres and volume ratios were evaluated statistically.

RESULTS: The means of the pulp cavity/tooth volume and root canal/ root volume ratio of the maxillary central incisor in anterior open bite group were significantly greater than those in the normal group. The average location of Cres in the anterior open bite group was 0.6 mm (3.7%) apically from the normal group, measured from root apex. The difference was statistically significant (P < 0.01). There was a significant correlation between root canal/root volume ratio and locations of Cres (r = -0.780, P < 0.001).

CONCLUSIONS: The Cres in the hypofunctional group was located more apical than the functional group. As the pulp cavity volume increased, the levels of Cres apically shifted.

PMID:37269106 | DOI:10.1177/14653125231176575

Hand (N Y). 2023 Jun 2:15589447231175512. doi: 10.1177/15589447231175512. Online ahead of print.

ABSTRACT

BACKGROUND: The Digit Widget is an external fixation device that can be used to reverse proximal interphalangeal joint (PIPJ) contractures in the hand. Our hypothesis is that usage of the Digit Widget prior to fasciectomy in patients with severe Dupuytren’s proximal interphalangeal (PIP) contractures will result in short-term improvement and maintenance of the PIPJ contracture after fasciectomy.

METHODS: Patients who underwent placement of the Digit Widget soft tissue distractor prior to fasciectomy for Dupuytren’s disease were identified between January 2015 and December 2018. Multiple fingers were considered separately. Patient Reported Outcome Measurement Information System (PROMIS) Physical Function (PF), Pain Interference, and Depression scores were collected. Patients treated for contractures from etiologies other than Dupuytren’s were not included. Multiple linear regression was used to compare initial PIP contractures, PF scores, and final contractures.

RESULTS: There were 28 fingers in 24 patients with average age of 56 ± 12 (30.5-69.9) years. Initial mean PIPJ contracture was 81° (50°-120°), which had corrected to 23° at time of removal. Average time between application and fasciectomy was 58 (28-112) days. At final follow-up, average 449 (58-1641) days, the average contracture was 39° (0°-105°). Contracture immediately following fasciectomy was found to be strongly correlated with the contracture at final follow-up. There was no statistical relationship between final PROMIS PF scores and final change in contracture.

CONCLUSIONS: Digit Widget external fixation is an effective treatment for the correction of advanced PIPJ contractures related to Dupuytren’s disease, with an average of 52% improvement in contracture at 15 months.

PMID:37269101 | DOI:10.1177/15589447231175512

Hand (N Y). 2023 Jun 2:15589447231174481. doi: 10.1177/15589447231174481. Online ahead of print.

ABSTRACT

Opposition is an essential function of the human thumb to enable fine pinch and grip strength. Loss of opposition can be caused by both congenital and acquired pathology resulting in significant disability. This systematic review aims to compare the different techniques available to restore opposition. A systematic review of opponensplasty techniques was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines using PubMed, Embase, Medline, and Web of Science. Studies published in English before April 2021 and that reported on original outcomes of opponensplasty techniques used in the context of neurologic dysfunction were eligible for inclusion. A total of 641 articles were included, of which 42 texts were eligible for inclusion with a total cohort of 873 patients. The most commonly used transfers were palmaris longus (PL), extensor indicis proprius (EIP), and flexor digitorum superficialis (FDS). These transfers all demonstrated an improvement in range of motion, pinch strength, and Kapandji scores. Complication rates of 19% and 12% were reported with FDS and EIP transfers, respectively, predominantly related to donor site morbidity. A complication rate of 6% was observed with PL transfers, which was most commonly related to bowstringing. Heterogeneity of outcomes precluded a direct statistical comparison. There is significant heterogeneity in the literature reporting on opponensplasty techniques. There is limited capacity of direct comparison; however, FDS and EIP appear to demonstrate better functional outcomes, at the cost of higher complication rates. Each technique has specific complications and advantages and importance in patient counseling and discussion. Further prospective comparative studies are warranted.

PMID:37269095 | DOI:10.1177/15589447231174481