Nevin Manimala

Thyroid. 2023 Nov 2. doi: 10.1089/thy.2023.0456. Online ahead of print.

ABSTRACT

OBJECTIVE: Redifferentiation therapy (RDT) can restore radioactive iodine (RAI) uptake in differentiated thyroid cancer (DTC) cells to enable salvage I-131 therapy for previously RAI refractory (RAIR) disease. This study evaluated the clinical outcomes of patients that underwent RDT and identified clinicopathologic characteristics predictive of RAI restoration following RDT.

METHODS: This is a retrospective case series of 33 patients with RECIST-progressive metastatic RAIR-DTC who underwent RDT between 2017 and 2022 at the Mayo Clinic Rochester. All patients underwent genomic profiling and received MEK, RET or ALK inhibitors alone or combination BRAF-MEK inhibitors for 4 weeks. At week 3, those with increased RAI avidity in metastatic foci received high dose I-131 therapy. Baseline and clinicopathologic outcomes were comprehensively reviewed.

RESULTS: Of the 33 patients, 57.6% had restored RAI uptake following RDT (Redifferentiated subgroup). 42.1% (8/19) with papillary thyroid cancers (PTC), 100% (4/4) with invasive encapsulated follicular variant PTCs (IEFV-PTC), and 100% (7/7) with follicular thyroid cancers (FTC) redifferentiated. All (11/11) RAS mutant tumors redifferentiated compared to 38.9% (7/18) with BRAF mutant disease (6 PTC and 1 IEFV-PTC). 76.5% (13/17) of redifferentiated and 66.7% (8/12) of non-redifferentiated patients achieved a best overall RECIST response of stable disease (SD) or non-complete response/non-progressive disease. Both subgroups had a median 12% tumor shrinkage at three weeks on drug(s) alone. The redifferentiated subgroup, following high dose I-131 therapy, achieved an additional median 20% tumor reduction at 6 months after RDT. There were no statistically significant differences between both groups in progression free survival (PFS), time to initiation of systemic therapy and time to any additional therapy. Of the entire cohort, 6.1% (2/33) experienced histologic transformation to anaplastic thyroid cancer and 15.1% (5/33) died, all had redifferentiated following RDT and received I-131 therapy.

CONCLUSION: RDT has the potential to restore RAI avidity and induce RECIST responses following I-131 therapy in select patients with RAIR-DTC, particularly those with RAS-driven ‘follicular’ phenotypes. In patients with PTC, none of the evaluated clinical outcomes differed statistically between the redifferentiated and non-redifferentiated subgroups. Further studies are needed to better characterize the long-term survival and/or safety outcomes of high-dose RAI following RDT, particularly whether it could be associated with histologic anaplastic transformation.

PMID:37917101 | DOI:10.1089/thy.2023.0456

J Endourol. 2023 Nov 2. doi: 10.1089/end.2023.0430. Online ahead of print.

ABSTRACT

BACKGROUND: Holmium laser enucleation of the prostate (HoLEP) has emerged as a new gold standard for treatment of benign prostatic hyperplasia (BPH); however, its steep learning curve hinders generalization of this technique. Therefore, there is a need for a benchtop HoLEP simulator to reduce this learning curve and provide training. We have developed a non-biohazardous HoLEP simulator using modern education theory and validated it in a multicenter study.

MATERIALS AND METHODS: Six experts established key components for a HoLEP simulator via a Delphi consensus over three rounds including 250 questions. Following consensus, a digital design was created and approved by experts, then used to fabricate a physical prototype using 3D printing and hydrogel molding. After a process of iterative prototype testing, experts completed a survey assessing the simulator with a five-point Likert scale for final approval. The approved model was validated with 56 expert and novice participants at seven institutions using subjective and objective performance metrics.

RESULTS: Consensus was reached on 85/250 questions and experts found the physical model to adequately replicate 82.5% of required features. Objective metrics were statistically significant (p<0.0001) when comparing experts and novices for procedure time (37.4 +/- 8.2 vs 16.7+/- 6.8 min), adenoma weight (79.6+/- 20.4 vs 36.2 +/- 9.9 gm), and complications (6 vs 22) respectively.

CONCLUSION: We have successfully completed a multi-center study to develop and validate a non-biohazardous benchtop simulator for HoLEP through modern education theory. A training curriculum including this simulator is currently under development.

PMID:37917099 | DOI:10.1089/end.2023.0430

Transl Vis Sci Technol. 2023 Nov 1;12(11):3. doi: 10.1167/tvst.12.11.3.

ABSTRACT

PURPOSE: The impact of functional vision, rather than visual acuity, on sleep disorders is not well understood. This study estimated the relationship between vision-related functional burden and sleep disorders among a nationally representative sample in the United States.

METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) 2005-2008 were analyzed, which included a total of 10,914 US adults 20 years and older. Sleep disorders and vision-related functional burden were measured by the NHANES questionnaire sleep disorders section and vision section, respectively. Logistic regression was used to explore the association between vision-related functional burden and sleep disorders.

RESULTS: A total of 9384 NHANES participants had complete functional vision and sleep disorders data. The mean age at baseline was 47.8 years, and the weighted prevalence of sleep disorders among adults with vision-related functional burden was 20.3%. After controlling for age, gender, race, smoking status, drinking frequency, general health condition, hypertension, diabetes, coronary heart disease, and depression, vision-related functional burden remained significantly associated with sleep disorders (adjusted odds ratio, 1.502; 95% confidence interval, 1.210-1.864; P < 0.001), whereas the association between presenting visual acuity and sleep disorders was not statistically significant.

CONCLUSIONS: Vision-related functional burden rather than impairment of visual acuity was related to the increased prevalence of sleep disorders in adults 20 years and older in the United States.

TRANSLATIONAL RELEVANCE: Our study provides insight into the relationship between functional vision and sleep disorders. It should be noted that individuals who report vision-related functional burden might be at risk of sleep disorders.

PMID:37917088 | DOI:10.1167/tvst.12.11.3

Transl Vis Sci Technol. 2023 Nov 1;12(11):4. doi: 10.1167/tvst.12.11.4.

ABSTRACT

PURPOSE: Evaluating bleb morphology is crucial after glaucoma filtering surgery. Advances in anterior segment optical coherence tomography (AS-OCT) allow for objective assessment. While various parameters differentiate functional from failed blebs, limited information exists regarding variations within functional blebs. This study aimed to identify factors influencing morphology of functional blebs following implantation of Preserflo MicroShunt.

METHODS: Eyes with functional blebs after Preserflo were retrospectively included. Age, gender, lens status, preoperative intraocular pressure (pre-IOP) and number of glaucoma medications were documented along with biometric measurements as axial length (AL), white-to-white distance, and anterior chamber depth. Postoperative data included time elapsed since surgery (TaS) and postoperative IOP (post-IOP). Bleb dimensions were measured using AS-OCT including maximal bleb height (MBH), width, length (MBL), bleb wall thickness (BWT), and bleb distance to limbus (DtL) along with dimensions of episcleral lake (maximal height, width [MLW], and length). Linear regression models were applied to correlate these parameters with bleb dimensions.

RESULTS: Included were 50 eyes from 50 patients. Mean IOP decreased from 25.3 ± 10.0 to 11.9 ± 3.0 mm Hg after 278.5 ± 221.9 days after surgery. MBH correlated negatively with age (unstandardized coefficients [uSC] = -0.012) and TaS (uSC = -0.001, P = 0.008 for both). BWT correlated negatively with age (uSC = -0.013, P = 0.02), MBL with AL (uSC = -0.566, P = 0.01) and MLW with pre-IOP (uSC = -0.073, P = 0.02). DtL exhibited a positive correlation with post-IOP (uCS = 0.136, P = 0.02).

CONCLUSIONS: Morphology of functional blebs might be influenced by multiple factors such as age, TaS, AL, and pre- and post-IOP.

TRANSLATIONAL RELEVANCE: Age, time after surgery, axial length, and preoperative and postoperative IOP could affect the morphology of a functional bleb; hence, these factors should be taken into consideration when making treatment decisions.

PMID:37917087 | DOI:10.1167/tvst.12.11.4

Transl Vis Sci Technol. 2023 Nov 1;12(11):6. doi: 10.1167/tvst.12.11.6.

ABSTRACT

PURPOSE: Glaucoma is an eye-brain axis disorder characterized by loss of retinal ganglion cells (RGCs). Although the role of intraocular pressure (IOP) elevation in glaucoma has been established, the reduction of oxidative stress and inflammation has emerged as a promising target for neuronal tissue-supporting glaucoma management. Therefore, we evaluated the effect of a proprietary spearmint extract (SPE) on RGC density, activity, and neuronal health markers in a rat model of hypertensive glaucoma.

METHODS: Animals were divided in four groups: untreated healthy control and three glaucomatous groups receiving orally administered vehicle, SPE-low dose, or SPE-high dose for 28 days. Ocular hypertension was induced through intracameral injection of methylcellulose at day 15. At day 29, rats underwent electroretinogram (ERG) recordings, and retinas were analyzed for RGC density and markers of neural trophism, oxidative stress, and inflammation.

RESULTS: SPE exerted dose-dependent response benefits on all markers except for IOP elevation. SPE significantly improved RGC-related ERG responses, cell density, neurotrophins, oxidative stress, and inflammation markers. Also, in SPE-high rats, most of the parameters were not statistically different from those of healthy controls.

CONCLUSIONS: SPE, a plant-based, polyphenolic extract, could be an effective nutritional support for neuronal tissues.

TRANSLATIONAL RELEVANCE: These results suggest that SPE not only may be a complementary approach in support to hypotensive treatments for the management of glaucoma but may also serve as nutritional support in other ocular conditions where antioxidant, anti-inflammatory, and neuroprotective mechanism are often disrupted.

PMID:37917085 | DOI:10.1167/tvst.12.11.6

JAMA Oncol. 2023 Nov 2. doi: 10.1001/jamaoncol.2023.4519. Online ahead of print.

ABSTRACT

IMPORTANCE: False-positive mammography results are common. However, long-term outcomes after a false-positive result remain unclear.

OBJECTIVES: To examine long-term outcomes after a false-positive mammography result and to investigate whether the association of a false-positive mammography result with cancer differs by baseline characteristics, tumor characteristics, and time since the false-positive result.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, matched cohort study was conducted in Sweden from January 1, 1991, to March 31, 2020. It included 45 213 women who received a first false-positive mammography result between 1991 and 2017 and 452 130 controls matched on age, calendar year of mammography, and screening history (no previous false-positive result). The study also included 1113 women with a false-positive result and 11 130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study. Statistical analysis was performed from April 2022 to February 2023.

EXPOSURE: A false-positive mammography result.

MAIN OUTCOMES AND MEASURES: Breast cancer incidence and mortality.

RESULTS: The study cohort included 497 343 women (median age, 52 years [IQR, 42-59 years]). The 20-year cumulative incidence of breast cancer was 11.3% (95% CI, 10.7%-11.9%) among women with a false-positive result vs 7.3% (95% CI, 7.2%-7.5%) among those without, with an adjusted hazard ratio (HR) of 1.61 (95% CI, 1.54-1.68). The corresponding HRs were higher among women aged 60 to 75 years at the examination (HR, 2.02; 95% CI, 1.80-2.26) and those with lower mammographic breast density (HR, 4.65; 95% CI, 2.61-8.29). In addition, breast cancer risk was higher for women who underwent a biopsy at the recall (HR, 1.77; 95% CI, 1.63-1.92) than for those without a biopsy (HR, 1.51; 95% CI, 1.43-1.60). Cancers after a false-positive result were more likely to be detected on the ipsilateral side of the false-positive result (HR, 1.92; 95% CI, 1.81-2.04) and were more common during the first 4 years of follow-up (HR, 2.57; 95% CI, 2.33-2.85 during the first 2 years; HR, 1.93; 95% CI, 1.76-2.12 at >2 to 4 years). No statistical difference was found for different tumor characteristics (except for larger tumor size). Furthermore, associated with the increased risk of breast cancer, women with a false-positive result had an 84% higher rate of breast cancer death than those without (HR, 1.84; 95% CI, 1.57-2.15).

CONCLUSIONS AND RELEVANCE: This study suggests that the risk of developing breast cancer after a false-positive mammography result differs by individual characteristics and follow-up. These findings can be used to develop individualized risk-based breast cancer screening after a false-positive result.

PMID:37917078 | DOI:10.1001/jamaoncol.2023.4519

Popul Health Manag. 2023 Nov 2. doi: 10.1089/pop.2023.0162. Online ahead of print.

ABSTRACT

The rise in health care costs, caused by older and more complex patient populations, requires Population Health Management approaches including risk stratification. With risk stratification, patients are assigned individual risk scores based on medical records. These patient stratifications focus on future high costs and expensive care utilization such as hospitalization, for which different models exist. With this study, the research team validated the accuracy of risk prediction scores for future hospitalization and high health care costs, calculated by the Adjusted Clinical Group (ACG)’s risk stratification models, using Dutch primary health care data registries. In addition, they aimed to adjust the US-based predictive models for Dutch primary care. The statistical validity of the existing models was assessed. In addition, the underlying prediction models were trained on 95,262 patients’ data from de Zoetermeer region and externally validated on data of 48,780 patients from Zeist, Nijkerk, and Urk. Information on age, sex, number of general practitioner visits, International Classification of Primary Care coded information on the diagnosis and Anatomical Therapeutic Chemical Classification coded information on the prescribed medications, were incorporated in the model. C-statistics were used to validate the discriminatory ability of the models. Calibrating ability was assessed by visual inspection of calibration plots. Adjustment of the hospitalization model based on Dutch data improved C-statistics from 0.69 to 0.75, whereas adjustment of the high-cost model improved C-statistics from 0.78 to 0.85, indicating good discrimination of the models. The models also showed good calibration. In conclusion, the local adjustments of the ACG prediction models show great potential for use in Dutch primary care.

PMID:37917048 | DOI:10.1089/pop.2023.0162

Euro Surveill. 2023 Nov;28(44). doi: 10.2807/1560-7917.ES.2023.28.44.2300019.

ABSTRACT

BackgroundThe NHS Test and Trace (NHSTT) programme was established in May 2020 in England to deliver SARS-CoV-2 testing and contact tracing in order to identify infected individuals and reduce COVID-19 spread. To further control transmission, people identified as contacts were asked to self-isolate for 10 days and test only if they became symptomatic. From March 2021, eligibility criteria for PCR testing expanded to include asymptomatic contacts of confirmed cases.AimTo analyse testing patterns of contacts before and after the change in testing guidance in England to assess the impact on PCR testing behaviour with respect to symptom status and contact type.MethodsTesting and contact tracing data were extracted from the national data systems and linked. Subsequently, descriptive statistical analysis was applied to identify trends in testing behaviour.ResultsBetween 1 January and 31 July 2021, over 5 million contacts were identified and reached by contact tracers; 42.3% took a PCR test around the time they were traced. Overall positivity rate was 44.3% and consistently higher in symptomatic (60-70%) than asymptomatic (around 20%, March-June) contacts. The proportion of tests taken by asymptomatic contacts increased over time, especially after the change in testing guidance. No link was observed between uptake of PCR tests and vaccination coverage. Fully vaccinated contacts showed lower positivity (23.8%) than those with one dose (37.2%) or unvaccinated (51.0%).ConclusionAlmost 1 million asymptomatic contacts were tested for SARS-CoV-2, identifying 214,056 positive cases, demonstrating the value of offering PCR testing to this group.

PMID:37917031 | DOI:10.2807/1560-7917.ES.2023.28.44.2300019

J Stud Alcohol Drugs. 2023 Oct 30. doi: 10.15288/jsad.23-00055. Online ahead of print.

ABSTRACT

OBJECTIVE: Understanding transitions in nicotine and cannabis use has implications for prevention and efforts to reduce harmful use. Focusing on cross-substance associations, we examined how use of one substance was associated with year-to-year transitions in frequency of use of the other among young adults in the context of legalized nonmedical cannabis.

METHOD: A statewide sample from Washington (N = 4,039; ages 18-25 at baseline) provided up to three years of annual data on past-month cannabis use and nicotine use (tobacco cigarettes and e-cigarettes/vaping). Manifest Markov models examined how use of each substance was associated with transitions in the other across categories of past-month no use, occasional use (1-19 days), and frequent use (20+ days).

RESULTS: Occasional and frequent nicotine use (vs. no use) predicted higher probability of transitioning from no cannabis use to occasional or frequent cannabis use and from occasional use to frequent use, while associations with cessation and de-escalation were inconsistent in direction, small in magnitude, and not statistically significant. Cannabis use positively predicted onset of nicotine use, and associations of cannabis use with escalation from occasional to frequent nicotine use, de-escalation in use, and cessation in use were small and inconsistent in direction.

CONCLUSIONS: The findings corroborate prior research on cannabis and nicotine use as risk factors to address in prevention efforts. The findings do not provide strong support for prioritization of dual abstinence in efforts to encourage reductions in or cessation of cannabis or nicotine use among young adults.

PMID:37917015 | DOI:10.15288/jsad.23-00055

J Anat. 2023 Nov 2. doi: 10.1111/joa.13967. Online ahead of print.

ABSTRACT

Muscle volume must increase substantially during childhood growth to generate the power required to propel the growing body. One unresolved but fundamental question about childhood muscle growth is whether muscles grow at equal rates; that is, if muscles grow in synchrony with each other. In this study, we used magnetic resonance imaging (MRI) and advances in artificial intelligence methods (deep learning) for medical image segmentation to investigate whether human lower leg muscles grow in synchrony. Muscle volumes were measured in 10 lower leg muscles in 208 typically developing children (eight infants aged less than 3 months and 200 children aged 5 to 15 years). We tested the hypothesis that human lower leg muscles grow synchronously by investigating whether the volume of individual lower leg muscles, expressed as a proportion of total lower leg muscle volume, remains constant with age. There were substantial age-related changes in the relative volume of most muscles in both boys and girls (p < 0.001). This was most evident between birth and five years of age but was still evident after five years. The medial gastrocnemius and soleus muscles, the largest muscles in infancy, grew faster than other muscles in the first five years. The findings demonstrate that muscles in the human lower leg grow asynchronously. This finding may assist early detection of atypical growth and allow targeted muscle-specific interventions to improve the quality of life, particularly for children with neuromotor conditions such as cerebral palsy.

PMID:37917014 | DOI:10.1111/joa.13967