Πέμπτη 16 Δεκεμβρίου 2021

A New Dynamic Response to Therapy Assessment in Postoperative Patients With Low-Risk Differentiated Thyroid Cancer Treated Without Radioactive Iodine

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Front Oncol. 2021 Nov 29;11:764258. doi: 10.3389/fonc.2021.764258. eCollection 2021.

ABSTRACT

BACKGROUND: Total thyroidectomy (TT) or lobectomy without radioactive iodine (RAI) is becoming a common management for patients with low-risk differentiated thyroid cancer (DTC). However, the assessment of response to therapy for these patients remains controversial. The aim of this study was to propose and validate a new dynamic evaluation strategy to assess the response to therapy in pat ients with low-risk DTC treated with TT or lobectomy but without RAI.

METHODS: We performed a retrospective analysis of 543 adult patients with low-risk DTC who underwent TT or lobectomy without RAI therapy. Follow-up consisted of trends of serum thyroglobulin (Tg), anti-thyroglobulin antibody (TgAb) levels and neck ultrasonography (US) were conducted every 6-24 months. Response to therapy assessments were defined as excellent response, biochemical incomplete response, structural incomplete response, and indeterminate response according to the follow-up findings.

RESULTS: At a median follow-up of 51 months (range 33-66 months), 517 (95%) had excellent response, while the other 26 had either biochemical incomplete response (an increasing trend of suppressed serum Tg levels, n=9; an increasing trend of TgAb levels, n=3) or indeterminate response (a stable or decreasing trend of suppressed serum Tg levels, but a stable positive trend of TgAb levels, n=14). No patients had s tructural incomplete response or no deaths related to thyroid cancer. The risk of incomplete response was significantly higher in lobectomy than in TT (p<0.001).

CONCLUSION: Our study proposed and validated a new dynamic response to therapy assessment depending on trends of suppressed serum Tg, TgAb levels, and neck US findings which could be an appropriate tool for postoperative follow-up in low-risk DTC patients without RAI therapy. Our findings provided further evidence to support no routine recommendation of RAI after surgery in low-risk DTC.

PMID:34912712 | PMC:PMC8667687 | DOI:10.3389/fonc.2021.764258

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90-Day Bundled Payment Simulation, Health Care Utilization, and Complications following Craniopharyngioma Resection in Adult Patients

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0041-1740395

Context Bundled payment and health care utilization models inform cost optimization and surgical outcomes. Economic analysis of payment plans for craniopharyngioma resection is unknown. Objective This study aimed to identify impact of endocrine and nonendocrine complications (EC and NEC, respectively) on health care utilization and bundled payments following craniopharyngioma resection. Design This study is presented as a retrospective cohort analysis (2000–2016) with 2 years of follow-up. Setting The study included national inpatient hospitalization and outpatient visits. Patients Patients undergoing craniopharyngioma resection were divided into the following four groups: group 1, no complications (NC); group 2, only EC; group 3, NEC; and group 4, both endocrine and nonendocrine complications (ENEC). Interventions This study investigated transphenoidal or subfrontal approach for tumor resection. Main Outcome Hospital readmission, health care utilization up to 24 months following discharge, and 90-day bundled payment performances are primary outcomes of this study. Results Median index hospitalization payments were significantly lower for patients in NC cohort ($28,672) compared with those in EC ($32,847), NEC ($36,259), and ENEC ($32,596; p < 0.0001). Patients in ENEC incurred higher outpatient services and overall median payments at 6 months (NC: 38,268; EC: 49,844; NEC: 68,237; and ENEC: 81,053), 1 year (NC: 46,878; EC: 58,210; NEC: 81,043; and ENEC: 94,768), and 2 years (NC: 58,391; EC: 70,418; NEC: 98,838; and ENEC: 1,11,841; p < 0.0001). The 90-day median bundled payment was significantly different among the cohorts with the highest in ENEC ($60,728) and lowest in the NC ($33,089; p < 0.0001). Conclusion ENEC following surgery incurred almost two times the overall median payments at 90 days, 6 months, 1 year. and 2 years compared with those without complications. Bundled payment model may not be a feasible option in this patient population. Type of complications and readmission rates should be considered to optimize payment model prediction following craniopharyngioma resection.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Risk of Diabetes in Patients with Long-Standing Graves' Disease: A Longitudinal Study

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Endocrinol Metab (Seoul). 2021 Dec 16. doi: 10.3803/EnM.2021.1251. Online ahead of print.

ABSTRACT

BACKGROUND: The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies.

METHODS: The risk of diabetes in patients with Graves' disease treated with antithyroid dru gs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group.

RESULTS: A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019).

CONCLUSION: The risk of diabetes was significantly higher in patients with long-standing Graves' disease than in t he general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

PMID:34915605 | DOI:10.3803/EnM.2021.1251

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Τετάρτη 15 Δεκεμβρίου 2021

Identification of heterogeneity and prognostic key genes associated with uveal melanoma using single-cell RNA-sequencing technology

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Uveal melanoma (UM) is the most common intraocular malignancy in adults. The prognosis is poor once metastasis has developed. The treatment of metastatic UM remains challenging nowadays due to lacking a deep understanding of the biological characteristics of this disease. Here, we revealed the cell subpopulations w ith distinct functional status and the existence of cells with high invasive potential within heterogeneous primary and metastatic UM. The single-cell sequencing data were retrieved from GSE139829 and GSE138433, through which we identified a new cell cluster related to metastatic UM as a unique type of immune cell. The cell–cell communication was conducted by 'Cellchat' to understand the cell crosstalk between these immune cells and their surrounding cells. The crucial signals contributing most to outgoing or incoming signaling of this cell group were identified to reveal the crucial pathway genes. Furthermore, we judged the prognostic value of these candidates on the basis of the data downloaded from The Cancer Genome Atlas. The results demonstrated that the increased IL10, SELPLG, EPHB and ITGB2 signaling pathways could be promising predicting factors for the patient prognosis in UM. Conclusively, we discover the potential key signals of UM for occurrence and metastasis, and also provide a theoretical basis for judging whether there is a high risk of metastasis or recurrence. * Songlin Sun and Rui Shi contributed equally to the writing of this article. Received 25 May 2021 Accepted 24 August 2021 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to Fengyuan Sun, PhD, MD, Tianjin Medical University Eye Hospital, Xiqing District, No.251 Fukang Road, Tianjin 300384, Tianjin, China, Tel: +086 022 86428810; e-mail: tianjiny2020@163.com Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Thyroid Cancer Incidence Trends

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Objective

To analyze thyroid cancer incidence trends among Filipinos relative to non-Filipino Asians and non-Hispanic Whites in the US.

Study Design

Population-based analysis of cancer incidence data.

Methods

Population-based analysis of cancer incidence data from Surveillance, Epidemiology, and End Results 9 detailed Asian/Pacific Islander subgroup incidence and population datasets. Adult patients aged 20 and older with thyroid cancer diagnosed in 2004 to 2014 were included. Annual percent change (APC) of the incidence rates were calculated using joinpoint regression analysis.

Results

The incidence rates were 19.57 (95% CI 19.03–20.12) per 100,000 for Filipinos, 10.45 (95% CI 10.22–10.68) per 100,000 for non-Filipino Asians, and 13.94 (95% CI 13.85–14.02) per 100,000 for non-Hispanic Whites. The highest increase was seen among non-Hispanic Whites (average APC 5.04, 95% CI 4.61–5.46). Incidence rates of tumors ≤ 2 cm remained stable among Filipinos but increased in non-Filipino Asians (average APC 5.38, 95% CI 2.51–8.34) and non-Hispanic Whites (average APC 5.81 95% CI 4.52–7.11).

Conclusion

Filipinos have high incidence of thyroid cancer compared with other racial/ethnic groups. However, non-Hispanic Whites have the highest increase in incidence rates, resulting in a significant narrowing of the gap in incidence rates between Filipinos and non-Hispanic Whites. This is most likely due to enhanced detection of small tumors in non-Hispanic Whites. Laryngoscope, 2021

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Association between olfactory dysfunction and COVID-19 severity: A prospective study in a highly complex hospital in Peru

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Ear Nose Throat J. 2021 Dec 15:1455613211066691. doi: 10.1177/01455613211066691. Online ahead of print.

ABSTRACT

INTRODUCTION: Olfactory dysfunction has been included among the early symptoms of coronavirus disease (COVID-19). Evidence suggests that a relationship exists between the duration of olfaction disorders and the probability of developing severe COVID-19. Given the scope of the COVID-19 pandemic, this study aimed to determine the frequency of smell alteration and it s association with the severity of COVID-19 in a referral hospital in Peru, which is one of the most affected countries in the Latin American region.

MATERIALS AND METHODS: This study was an observational, prospective cohort study that included patients with COVID-19 who were treated at the Hospital Nacional Edgardo Rebagliati Martins from August to November 2020. To assess the association, the chi-square test of independence or Fisher's exact test was performed. The outcome variable was COVID-19 severity, and the exposure variable was olfactory dysfunction. The first data collection was in the emergency department and the follow-up was via telephone.

RESULTS: A total of 179 patients were included. The mean age was 61.6 ± 15.5 years, and 129 patients (72.1%) were male. Olfactory dysfunction was observed in 43 patients (24%). An inverse association was found between age and olfactory dysfunction (P = .002). No significant association was found between COVID-19 sev erity level and olfactory alteration (P = .056). However, a direct association was found between COVID-19 severity and age (P = .003), cough (P < .001), and respiratory distress (P = .003).

CONCLUSION: This study did not find any association between the severity of COVID-19 and olfactory dysfunction. It showed a low incidence rate of smell alteration compared with studies from other regions. Moreover, smell alteration was associated with younger age.

PMID:34908507 | DOI:10.1177/01455613211066691

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Concomitant Variants in NF1, LZTR1, and GNAZ Genes Probably Contribute to the Aggressiveness of Plexiform Neurofibroma and Warrant Treatment with MEK Inhibitor

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Abstract

Neurofibromatosis 1 (NF1) is caused by germline mutations in the NF1 gene and manifests as proliferation of various tissues, including plexiform neurofibromas. The plexiform neurofibroma phenotype varies from indolent to locally aggressive, suggesting contributions of other modifiers in addition to somatic loss of NF1. Here, we investigated a life-threatening plexiform neurofibroma in a 9-month-old female infant with NF1. Germline mutations in two Rasopathy-associated genes were identified using whole exome sequencing - a de-novo pathogenic variant in the NF1 gene, and a known pathogenic variant in the LZTR1 gene. Somatic analysis of the plexiform neurofibroma revealed NF1 loss of heterozygosity and a variant in GNAZ, a gene encoding a G Protein Coupled Receptor. Cells expressing mutant GNAZ exhibited increased ERK 1,2 activation compared to those expressing wild type GNAZ. Taken together, we suggest the variants in NF1, LZRT1, and GNAZ act synergistically in our patient, leading to MAPK pathway activation and contributing to the severity of the patient's plexiform neurofibromatosis. After treatment with the MEK inhibitor, trametinib, a prominent clinical improvement was observed in this patient. This case study contributes to the knowledge of germline and somatic non-NF1 variants affecting the NF1 clinical phenotype and supports use of personalized, targeted therapy.

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