TNF-Alpha Inhibitors and Ustekinumab for the Treatment of Psoriasis: Therapeutic Utility in the Era of IL-17 and IL-23 Inhibitors

Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and comorbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups.

Malignancy Risk Stratification of Thyroid Nodules According to Echotexture and Degree of Hypoechogenicity: A Multicenter Validation Study

Purpose Various risk stratification systems show some discrepancies in the ultrasound (US) lexicon of nodule echotexture and hypoechogenicity. This study aimed to determine the malignancy risk of thyroid nodules according to their echotexture and degree of hypoechogenicity in a multicenter dataset.Methods From June to September 2015, 5,601 thyroid nodules (≥ 1.0 cm) in 4,989 consecutive patients who underwent thyroid US and with a final diagnoses from 26 institutions were evaluated. Thyroid nodules were stratified according to the US echotexture (homogeneous vs. heterogeneous) and degree of hypoechogenicity (mild, moderate, or marked). We then calculated malignancy risk and compared four subgroups stratified with nodule composition and presence of suspicious features.Results Heterogeneous hypoechoic nodules showed a significantly higher malignancy risk than heterogeneous isoechoic nodules (P ≤ 0.017) except in partially cystic nodules. There was no significant difference in malignancy risk between homogeneous vs. heterogeneous hypoechoic nodules (P ≥ 0.086) and between homogeneous vs. heterogeneous iso- or hyperechoic nodules (P ≥ 0.05) except in partially cystic nodules without suspicious features. The malignancy risks of both homogeneous and heterogeneous iso- or hyperechoic nodules were low to intermediate, depending on the presence of suspicious features. Regarding the degree of hypoechogenicity, there was no significant difference in malignancy risk between markedly and moderately hypoechoic nodules in all subgroups (P ≥ 0.48). Marked or moderately hypoechoic nodules showed a significantly higher risk than mild hypoechoic (P ≤ 0.016) and iso- or hyperechoic (P < .001) nodules. Conclusions The predominant echogenicity effectively stratifies the malignancy risk of nodules with heterogeneous echotexture. For malignancy risk stratification, the degree of nodules’ hypoechogenicity could be grouped as mild vs. moderate to marked hypoechogenicity.

Performance of current ultrasound-based malignancy risk stratification systems for thyroid nodules in patients with follicular neoplasms

Objectives To investigate the ability of the currently used ultrasound-based malignancy risk stratification systems for thyroid neoplasms (ATA, AACE/ACE/AME, K-TIRADS, EU-TIRADS, ACR-TIRADS and C-TIRADS) in distinguishing follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA). Additionally, we evaluated the ability of these systems in correctly determining the indication for biopsy. Methods Three hundred twenty-nine follicular neoplasms with definitive postoperative histopathology were included. The nodules were categorized according to each of six stratification systems, based on ultrasound findings. We dichotomized nodules into the positive predictive group of FTC (high and intermediate risk) and negative group of FTC based on the classification results. Missed biopsy was defined as neoplasms that were diagnosed as FTCs but for which biopsy was not indicated based on lesion classification. Unnecessary biopsy was defined as neoplasms that were diagnosed as FTAs but for whom biopsy was considered indicated based on classification. The diagnostic performance and missed and unnecessary biopsy rates were evaluated for each stratification system. Results The area under the curve of each system for distinguishing follicular neoplasms was < 0.700 (range, 0.511–0.611). The missed biopsy rates were 9.0–22.4%. The missed biopsy rates for lesions ≤ 4 cm and lesions sized 2–4 cm were 16.2–35.1% and 0–20.0%, respectively. Unnecessary biopsy rates were 65.3–93.1%. In ≤ 4 cm group, the unnecessary biopsy rates were 62.2–89.7%. Conclusion The malignancy risk stratification systems can select appropriate nodules for biopsy in follicular neoplasms, while they have limitations in distinguishing follicular neoplasms and reducing unnecessary biopsy. Specific stratification systems and recommendations should be established for follicular neoplasms. Key Points • Current ultrasound-based malignancy risk stratification systems of thyroid nodules had low efficiency in the characterization of follicular neoplasms. • The adopted stratification systems showed acceptable performance for selecting FTC for biopsy but unsatisfactory performance for reducing unnecessary biopsy.

Modified Models for Predicting Malignancy Using Ultrasound Characters Have High Accuracy in Thyroid Nodules With Small Size

To assess the malignancy risk of thyroid nodules, ten ultrasound characteristics are suggested as key diagnostic markers. The European Thyroid Association Guidelines (EU-TIRADS) and 2015 American Thyroid Association Management Guidelines (2015ATA) are mainly used for ultrasound malignancy risk stratification, but both are less accurate and do not appropriatetly classify high risk patients in clinical examination. Previous studies focus on papillary thyroid carcinoma (PTC), but follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC) remained to be characterized. Thus, this study aimed to determine the diagnostic accuracy and establish models using all ultrasound features including the nodule size for predicting the malignancy of thyroid nodules (PTC, FTC, and MTC) in China. We applied logistic regression to the data of 1,500 patients who received medical treatment in Shanghai and Fujian. Ultrasound features including taller-than-wide shape and invasion of the thyroid capsule showed high odds ratio (OR 19.329 and 4.672) for PTC in this dataset. Invasion of the thyroid also showed the highest odds ratio (OR = 8.10) for MTC. For FTC, the halo sign has the highest odds ratio (OR = 13.40). Four ultrasound features revealed distinct OR in PTC nodule groups with different sizes. In this study, we constructed a logistic model with accuracy up to 80%. In addition, this model revealed more accuracy than TIRADS in 4b and 4c category nodules. Hence, this model could well predict malignancy in small nodules and classify high-risk patients.

Malignancy risk of indeterminate mammographic calcification in symptomatic breast clinics

BackgroundTo explore the potential risk factors predicting malignancy in patients with indeterminate incidental mammographic microcalcification and to evaluate the short-term risk of developing malignancy.MethodsBetween January 2011 and December 2015, one hundred and fifty (150) consecutive patients with indeterminate mammographic microcalcifications who had undergone stereotactic biopsy were evaluated. Clinical and mammographic features were recorded and compared with histopathological biopsy results. In patients with malignancy, postsurgical findings and surgical upgrade, if any, were recorded. Linear regression analysis (SPSS V.25) was used to evaluate significant variables predicting malignancy. OR with 95% CIs was calculated for all variables. All patients were followed up for a maximum of 10 years. The mean age of the patients was 52 years (range 33–79 years).ResultsThere were a total of 55 (37%) malignant results in this study cohort. Age was an independent predictor of breast malignancy with an OR (95% CI) of 1.10 (1.03 to 1.16). Mammographic microcalcification size, pleomorphic morphology, multiple clusters and linear/segmental distribution were significantly associated with malignancy with OR (CI) of 1.03 (1.002 to 1.06), 6.06 (2.24 to 16.66), 6.35 (1.44 to 27.90) and 4.66 (1.07 to 20.19). The regional distribution of microcalcification had an OR of 3.09 (0.92 to 10.3), but this was not statistically significant. Patients with previous breast biopsies had a lower risk of breast malignancy than patients with no prior biopsy (p=0.034).ConclusionMultiple clusters, linear/segmental distribution, pleomorphic morphology, size of mammographic microcalcifications and increasing age were independent predictors of malignancy. Having a previous breast biopsy did not increase malignancy risk.