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"Issa, Peter P."
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The Diagnostic Performance of Ultrasonography in the Evaluation of Extrathyroidal Extension in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis
by
Toraih, Eman
,
Albuck, Aaron L.
,
Aboueisha, Mohamed
in
Carcinoma, Papillary - pathology
,
Humans
,
Odds Ratio
2022
Extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) is an indication of disease progression and can influence treatment aggressiveness. This meta-analysis assesses the diagnostic accuracy of ultrasonography (US) in detecting ETE. A systematic review and meta-analysis were performed by searching PubMed, Embase, and Cochrane for studies published up to April 2022. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. The areas under the curve (AUC) for summary receiver operating curves were compared. A total of 11 studies analyzed ETE in 3795 patients with PTC. The sensitivity of ETE detection was 76% (95%CI = 74–78%). The specificity of ETE detection was 51% (95%CI = 49–54%). The DOR of detecting ETE by US was 5.32 (95%CI = 2.54–11.14). The AUC of ETE detection was determined to be 0.6874 ± 0.0841. We report an up-to-date analysis elucidating the diagnostic accuracy of ETE detection by US. Our work suggests the diagnostic accuracy of US in detecting ETE is adequate. Considering the importance of ETE detection on preoperative assessment, ancillary studies such as adjunct imaging studies and genetic testing should be considered.
Journal Article
Helicobacter Pylori: A Review of Current Treatment Options in Clinical Practice
by
Malone, Kevin
,
Ahmadzadeh, Shahab
,
Eubanks, Treniece N.
in
Antibacterial agents
,
Antibiotics
,
Antimicrobial agents
2022
Background: When prescribing antibiotics, infection eradication rates, local resistance rates, and cost should be among the most essential considerations. Helicobacter pylori is among the most common infections worldwide, and it can lead to burdensome sequela for the patient and the healthcare system, without appropriate treatment. Due to constantly fluctuating resistance rates, regimens must be constantly assessed to ensure effectiveness. Methods: This was a narrative review. The sources for this review are as follows: searching on PubMed, Google Scholar, Medline, and ScienceDirect; using keywords: Helicobacter pylori, Treatment Options, Clinical Practice. Results: Multiple antibiotics are prescribed as part of the regimen to thwart high resistance rates. This can lead to unwanted adverse reactions and adherence issues, due to the amount and timing of medication administration, which also may contribute to resistance. Single-capsule combination capsules have reached the market to ease this concern, but brand-only may be problematic for patient affordability. Due to the previously mentioned factors, effectiveness and affordability must be equally considered. Conclusions: This review will utilize guidelines to discuss current treatment options and give cost considerations to elicit the most effective regimen for the patient.
Journal Article
Hashimoto’s Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas
by
Toraih, Eman
,
Corsetti, Ralph L.
,
Aboueisha, Mohamed
in
Biopsy
,
Decision making
,
Hashimoto’s thyroiditis
2022
Hashimoto’s thyroiditis (HT) (autoimmune thyroiditis) is a clinicopathological entity associated with chronic lymphocytic infiltration resulting in hypothyroidism. HT is a double-edged sword that increases the risk of papillary thyroid cancer (PTC), yet it serves as a protective factor for PTC progression. BRAF mutation in PTCs is associated with rapid cell growth, aggressive tumor characteristics, and higher mortality rates. Here, we aimed to analyze the influence of HT in patients with PTCs and its effect on lymph node metastasis (LNM) in BRAF mutant tumors. Adults diagnosed with PTC between 2008 and January 2021 were retrospectively included. A total of 427 patients, 128 of whom had underlying HT, were included. The HT group had significantly higher rates of microcarcinoma (49.2% vs. 37.5%, p = 0.025) and less lateral LNM (8.6% vs. 17.1%, p = 0.024). Interestingly, BRAF-mutated PTCs were found to have significantly less overall LNM (20.9% vs. 51%, p = 0.001), central LNM (25.6% vs. 45.1%, p = 0.040) and lateral LNM (9.3% vs. 29.4%, p = 0.010) in patients with HT when compared to those without underlying HT. HT was found to be an independent protective predictor of overall and lateral LNM. Altogether, HT was able to neutralize the effect of BRAF mutation and was determined to be an independent protective factor against LNM. Specifically, our work may influence treatment-aggressiveness decision making for endocrinologists, oncologists and surgeons alike.
Journal Article
Minoxidil weakens newly synthesized collagen in fibrotic synoviocytes from osteoarthritis patients
by
Sarkovich, Stefan
,
McTernan, Patrick
,
Longanecker, Andrew
in
Arthritis
,
Arthroplasty
,
Collagen type I
2023
Purpose
Synovial fibrosis (SFb) formation and turnover attributable to knee osteoarthritis (KOA) can impart painful stiffness and persist following arthroplasty. To supplement joint conditioning aimed at maximizing peri-operative function, we evaluated the antifibrotic effect of Minoxidil (MXD) on formation of pyridinoline (Pyd) cross-links catalyzed by
Plod2
-encoded lysyl hydroxylase (LH)2b that strengthen newly synthesized type-I collagen (COL1) in fibroblastic synovial cells (FSCs) from KOA patients. MXD was predicted to decrease Pyd without significant alterations to
Col1a1
transcription by FSCs stimulated with transforming growth factor (TGF)β1.
Methods
Synovium from 10 KOA patients grouped by SFb severity was preserved for picrosirius and LH2b histology or culture. Protein and RNA were purified from fibrotic FSCs after 8 days with or without 0.5 µM MXD and/or 4 ng/mL of TGFβ1. COL1 and Pyd protein concentrations from ELISA and expression of
Col1a1
,
Acta2
, and
Plod2
genes by qPCR were compared by parametric tests with α = 0.05.
Results
Histological LH2b expression corresponded to SFb severity. MXD attenuated COL1 output in KOA FSCs but only in the absence of TGFβ1 and consistently decreased Pyd under all conditions with significant downregulation of
Plod2
but minimal alterations to
Col1a1
and
Acta2
transcripts.
Conclusions
MXD is an attractive candidate for local antifibrotic pharmacotherapy for SFb by compromising the integrity of newly formed fibrous deposits by FSCs during KOA and following arthroplasty. Targeted antifibrotic supplementation could improve physical therapy and arthroscopic lysis strategies aimed at breaking down joint scarring. However, the effect of MXD on other joint-specific TGFβ1-mediated processes or non-fibrotic components requires further investigation.
Journal Article
Latency Trend Analysis as a Guide to Screening Malignancy Survivors for Second Primary Thyroid Cancer
by
Toraih, Eman
,
Haidari, Muhib
,
Trinh, Lily
in
Breast cancer
,
Cancer therapies
,
Care and treatment
2022
Primary cancer survivors have a higher risk of developing second primary thyroid cancer (SPTC). Patients with SPTC who survived primary malignancies, diagnosed from 1975 to 2016, were identified from the Surveillance, Epidemiology, and End Results (SEER) database (SEER 18 Registry). A total of 33,551 cancer cases were enrolled in the final analysis. Individuals with a primary malignancy were at a significant 90% increased risk of developing SPTC (SIR = 1.90, 95%CI = 1.86–1.93, p < 0.05) compared to the general population. More than half (54.7%) of SPTC diagnoses were made in the first three years after primary cancer diagnosis, and the most aggressive presentations of SPTC occurred within the first year following malignancy. A latency trend analysis identified persistent high risk for development of SPTC after diagnosis of lymphoma, leukemia, soft tissue tumors, kidney, breast, and uterine cancer; elevated 10-year risk for most cancers such as salivary gland, melanoma, stomach, lung, colon, ovarian, pancreas, prostate, and bladder; and high 5-year risk after cancers such as larynx, oral, orbit, bone, small intestine, and liver. Our latency period model identifying risk according to each type of primary cancer may aid clinicians in identifying at-risk patients to be screened for thyroid cancer and guide them in developing a surveillance plan according to the latency period attributed to a patient’s primary cancer.
Journal Article
Radiologist versus Non-Radiologist Detection of Lymph Node Metastasis in Papillary Thyroid Carcinoma by Ultrasound: A Meta-Analysis
2022
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer worldwide and is known to spread to adjacent neck lymphatics. Lymph node metastasis (LNM) is a known predictor of disease recurrence and is an indicator for aggressive resection. Our study aims to determine if ultrasound sonographers’ degree of training influences overall LNM detection. PubMed, Embase, and Scopus articles were searched and screened for relevant articles. Two investigators independently screened and extracted the data. Diagnostic test parameters were determined for all studies, studies reported by radiologists, and studies reported by non-radiologists. The total sample size amounted to 5768 patients and 10,030 lymph nodes. Radiologists performed ultrasounds in 18 studies, while non-radiologists performed ultrasounds in seven studies, corresponding to 4442 and 1326 patients, respectively. The overall sensitivity of LNM detection by US was 59% (95%CI = 58–60%), and the overall specificity was 85% (95%CI = 84–86%). The sensitivity and specificity of US performed by radiologists were 58% and 86%, respectively. The sensitivity and specificity of US performed by non-radiologists were 62% and 78%, respectively. Summary receiver operating curve (sROC) found radiologists and non-radiologists to detect LNM on US with similar accuracy (p = 0.517). Our work suggests that both radiologists and non-radiologists alike detect overall LNM with high accuracy on US.
Journal Article
The HCV-Melanoma Paradox: First Multi-Cohort and Molecular Net-Work Analysis Reveals Lower Incidence but Worse Outcomes—Integrating Clinical, Real-World, and In Silico Data
2024
Background and Objectives: The relationship between hepatitis C virus (HCV) infection and melanoma remains poorly understood. This study aimed to investigate the association between HCV and melanoma, assess outcomes in patients with both conditions, and explore potential molecular mechanisms connecting the two diseases. Materials and Methods: We conducted a retrospective cohort study of 142 melanoma patients, including 29 with HCV-related cirrhosis, and analyzed their clinical outcomes. For external validation, we used the TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched patients per group. An in silico analysis was performed to identify the molecular pathways linking HCV and melanoma. Results: In the retrospective cohort, HCV-positive melanoma patients showed an increased risk of early relapse (41.4% vs. 18.6%, p = 0.014), recurrence (65.5% vs. 39.8%, p = 0.020), and mortality (65.5% vs. 23.0%, p < 0.001) compared to HCV-negative patients. TriNetX data analysis revealed that HCV-positive patients had a 53% lower risk of developing melanoma (RR = 0.470, 95% CI: 0.443–0.498, p < 0.001). However, HCV-positive melanoma patients had higher all-cause mortality (HR = 1.360, 95% CI: 1.189–1.556, p < 0.001). An in silico analysis identified key molecular players, including IL-6 and CTLA4, in the HCV-melanoma network. Conclusions: While HCV infection may be associated with a lower risk of melanoma development, HCV-positive patients who develop melanoma have poorer outcomes. The identified molecular pathways provide potential targets for future research and therapeutic interventions.
Journal Article
Diagnostic utility of RAS mutation testing for refining cytologically indeterminate thyroid nodules
2024
mutations are prevalent in indeterminate thyroid nodules, but their association with malignancy risk and utility for diagnosis remains unclear. We performed a systematic review and meta-analysis to establish the clinical value of
mutation testing for cytologically indeterminate thyroid nodules. PubMed and Embase were systematically searched for relevant studies. Thirty studies comprising 13,328 nodules met the inclusion criteria. Random effects meta-analysis synthesized pooled estimates of
mutation rates, risk of malignancy with
positivity, and histologic subtype outcomes. The pooled mutation rate was 31 % (95 % CI 19-44 %) among 5,307 indeterminate nodules. N
mutations predominated at 67 % compared to H
(24 %) and K
(12 %). The malignancy rate with
mutations was 58 % (95 %CI=48-68 %).
positivity increased malignancy risk 1.7-fold (RR 1.68, 95 %CI=1.21-2.34, p=0.002), with significant between-study heterogeneity (I2=89 %). Excluding one outlier study increased the relative risk to 1.75 (95 %CI=1.54-1.98) and I2 to 14 %. Funnel plot asymmetry and Egger's test (p=0.03) indicated potential publication bias. Among
-positive malignant nodules, 38.6 % were follicular variant papillary carcinoma, 34.1 % classical variant, and 23.2 % follicular carcinoma. No statistically significant difference in the odds of harboring
mutation was found between subtypes. In conclusion,
mutation testing demonstrates clinical utility for refining the diagnosis of cytologically indeterminate thyroid nodules. Positivity confers a 1.7-fold increased malignancy risk, supporting use for personalized decision-making regarding surgery vs. monitoring. Follicular variant papillary carcinoma constitutes the most common
-positive malignant histological subtype. See also the graphical abstract(Fig. 1).
Journal Article
Ultraviolet Light Exposure Decreases Thyroid Cancer Risk: A National Perspective
by
Toraih, Eman
,
Lavorgna, Tessa R.
,
Issa, Peter P.
in
African Americans
,
Anti-oncogenes
,
Development and progression
2022
Ultraviolet (UV) light has been reported to have both pro-oncogenic and anti-oncogenic effects. Since patient pigmentation can influence the role of UV light exposure, we thought to investigate the recent trends in thyroid cancer incidence and survival with an emphasis on patient race and UV exposure. Patients diagnosed with thyroid cancer from the Surveillance, Epidemiology, and End Results (SEER) database were identified. A total of 284,178 patients were enrolled. Data were stratified according to population sex, race, and state. UV exposure data in Watt-Hours Per Square Meter for the state were obtained from the National Cancer Institute Cancer Atlas. Thyroid cancer incidence rate varied by race, ranging from 14.9 cases per 100,000 in Asian or Pacific Islanders and 14.7 per 100,000 in Caucasians, to 8.7 per 100,000 in African American and 8.0 per 100,000 in Native Americans. UV exposure was negatively correlated with thyroid cancer incidence when analyzed across all populations (r = −0.299, p = 0.035). UV exposure was most steeply negatively correlated with thyroid cancer rates in Black populations (r = −0.56, p < 0.001). Despite this, Black men had the worst 5-year survival rate when compared to other ethnic populations. Overall, UV exposure does not increase the risk of thyroid cancer and may serve as a protective factor in the development of thyroid cancer.
Journal Article
Radiofrequency Ablation of Indeterminate Thyroid Nodules: The First North American Comparative Analysis
by
Toraih, Eman
,
Buti, Yusef
,
Aboueisha, Mohamed
in
Ablation
,
Catheter Ablation - adverse effects
,
Comparative analysis
2022
Thyroid nodules can be classified as benign, malignant, or indeterminate, the latter of which make up 10–30% of nodules. Radiofrequency ablation (RFA) has become an attractive and promising therapy for the treatment of benign thyroid nodules. However, few studies have investigated the safety and efficacy of RFA for the management of indeterminate thyroid nodules. In this study, 178 patients with thyroid nodules diagnosed as benign (Bethesda II) or indeterminate (Bethesda III/IV) by preoperative cytopathological analysis were included. Patients in the benign and indeterminate cohorts had similar thyroid nodule volume reduction rates at 65.60% and 64.20%, respectively (p = 0.68). The two groups had similar nodular regrowth rates, at 11.2% for benign nodules and 9.40% for indeterminate nodules (p = 0.72). A total of three cases of transient dysphonia were reported. RFA of indeterminate thyroid nodules was comparable to that of benign thyroid nodules in all parameters of interest, including volume reduction rate. To our best knowledge, our work is the first North American analysis comparing benign and indeterminate thyroid nodules and suggests RFA to be a promising modality for the management of indeterminate thyroid nodules.
Journal Article