Detecting Drug-Drug Interactions in COVID-19 Patients.

COVID-19 patients with multiple comorbid illnesses are more likely to be using polypharmacy to treat their COVID-19 disease and comorbid conditions. Previous literature identified several DDIs in COVID-19 patients; however, various DDIs are unrecognized. This study aims to discover novel DDIs by conducting comprehensive research on the FDA Adverse Event Reporting System (FAERS) data from January 2020 to March 2021. We applied seven algorithms to discover DDIs. In addition, the Liverpool database containing DDI confirmed by clinical trials was used as a gold standard to determine novel DDIs in COVID-19 patients. The seven models detected 2,516 drug-drug pairs having adverse events (AEs), 49 out of which were confirmed by the Liverpool database. The remaining 2,467 drug pairs tested to be significant by the seven models can be candidate DDIs for clinical trial hypotheses. Thus, the FAERS database, along with informatics approaches, provides a novel way to select candidate drug-drug pairs to be examined in COVID-19 patients.

Machine Learning Approach Using Routine Immediate Postoperative Laboratory Values for Predicting Postoperative Mortality.

BACKGROUND: Several prediction models have been proposed for preoperative risk stratification for mortality. However, few studies have investigated postoperative risk factors, which have a significant influence on survival after surgery. This study aimed to develop prediction models using routine immediate postoperative laboratory values for predicting postoperative mortality. METHODS: Two tertiary hospital databases were used in this research: one for model development and another for external validation of the resulting models. The following algorithms were utilized for model development: LASSO logistic regression, random forest, deep neural network, and XGBoost. We built the models on the lab values from immediate postoperative blood tests and compared them with the SASA scoring system to demonstrate their efficacy. RESULTS: There were 3817 patients who had immediate postoperative blood test values. All models trained on immediate postoperative lab values outperformed the SASA model. Furthermore, the developed random forest model had the best AUROC of 0.82 and AUPRC of 0.13, and the phosphorus level contributed the most to the random forest model. CONCLUSIONS: Machine learning models trained on routine immediate postoperative laboratory values outperformed previously published approaches in predicting 30-day postoperative mortality, indicating that they may be beneficial in identifying patients at increased risk of postoperative death.

A Framework (SOCRATex) for Hierarchical Annotation of Unstructured Electronic Health Records and Integration Into a Standardized Medical Database: Development and Usability Study.

BACKGROUND: Although electronic health records (EHRs) have been widely used in secondary assessments, clinical documents are relatively less utilized owing to the lack of standardized clinical text frameworks across different institutions. OBJECTIVE: This study aimed to develop a framework for processing unstructured clinical documents of EHRs and integration with standardized structured data. METHODS: We developed a framework known as Staged Optimization of Curation, Regularization, and Annotation of clinical text (SOCRATex). SOCRATex has the following four aspects: (1) extracting clinical notes for the target population and preprocessing the data, (2) defining the annotation schema with a hierarchical structure, (3) performing document-level hierarchical annotation using the annotation schema, and (4) indexing annotations for a search engine system. To test the usability of the proposed framework, proof-of-concept studies were performed on EHRs. We defined three distinctive patient groups and extracted their clinical documents (ie, pathology reports, radiology reports, and admission notes). The documents were annotated and integrated into the Observational Medical Outcomes Partnership (OMOP)-common data model (CDM) database. The annotations were used for creating Cox proportional hazard models with different settings of clinical analyses to measure (1) all-cause mortality, (2) thyroid cancer recurrence, and (3) 30-day hospital readmission. RESULTS: Overall, 1055 clinical documents of 953 patients were extracted and annotated using the defined annotation schemas. The generated annotations were indexed into an unstructured textual data repository. Using the annotations of pathology reports, we identified that node metastasis and lymphovascular tumor invasion were associated with all-cause mortality among colon and rectum cancer patients (both P=.02). The other analyses involving measuring thyroid cancer recurrence using radiology reports and 30-day hospital readmission using admission notes in depressive disorder patients also showed results consistent with previous findings. CONCLUSIONS: We propose a framework for hierarchical annotation of textual data and integration into a standardized OMOP-CDM medical database. The proof-of-concept studies demonstrated that our framework can effectively process and integrate diverse clinical documents with standardized structured data for clinical research.

Can the basal serum thyroglobulin level be used to predict the recombinant human TSH-stimulated thyroglobulin level in differentiated patients with thyroid cancer?

This study investigated the correlation between basal thyroglobulin (Tg) and recombinant human thyroid-stimulating hormone (rhTSH)-stimulated Tg in differentiated patients with thyroid cancer, and sought to determine whether the basal Tg level predicts the rhTSH-stimulated Tg level.We retrospectively enrolled 177 patients with papillary thyroid cancer (mean age = 44 years; 50 males, 127 females) who received rhTSH before radioiodine therapy (RIT). Serum Tg levels were measured 7 days before the 1st rhTSH injection (basal Tg) and on the days of RIT (rhTSH-stimulated Tg). Patients were divided into 3 groups according to rhTSH-stimulated Tg cut-off levels of 2, 5, and 10 ng/mL. The correlation between basal Tg and rhTSH-stimulated Tg levels was assessed, and whether basal Tg was useful in predicting the rhTSH-stimulated Tg level was determined.A significant positive correlation was observed between basal and rhTSH-stimulated Tg levels (|rho| = 0.48, P < .0001). The basal Tg level had significant diagnostic ability in predicting an rhTSH-stimulated Tg level of 2 ng/mL or higher, and the optimal basal Tg level for this prediction was 0.3 ng/mL (AUC = 0.77, P < .0001). A basal Tg level of 0.5 ng/mL was optimal for predicting rhTSH-stimulated Tg levels of 5 ng/mL or higher (AUC = 0.81, P < .0001), and of 10 ng/mL or higher (AUC = 0.82, P = .0171).The basal Tg level was significantly correlated with the rhTSH-stimulated Tg level. If the basal Tg level is >0.3 or 0.5 ng/mL, then the rhTSH-stimulated Tg level can be expected to be sufficiently high to necessitate clinical examination.

Risk Factors for Indeterminate Response After Radioactive Iodine Therapy in Patients With Differentiated Thyroid Cancer.

PURPOSE: We investigated the risk factors of indeterminate response (IDR) in patients who underwent recombinant human thyroid-stimulating hormone (rhTSH)-aided radioactive iodine therapy (RAIT). METHODS: A total of 128 patients with papillary thyroid cancer were included in this retrospective study. The patients were classified into excellent response and IDR groups based on follow-up diagnostic whole-body scintigraphy (WBS) and TSH-stimulated thyroglobulin (Tg). Indeterminate response was defined as the presence of a faint uptake in the thyroid bed on the diagnostic WBS or a TSH-stimulated Tg detectable, but less than 10 ng/mL. Parameters that act as significant risk factors for IDR, including age, sex, stage, surgeon, time interval between surgery and RAIT, post-treatment WBS finding, urine iodine-to-creatinine ratio, TSH-unstimulated Tg, and rhTSH-stimulated Tg, were analyzed using a Cox proportional hazards regression method. RESULTS: After treatment, 64 patients showed IDR. Recombinant human TSH-stimulated Tg was the only independent risk factor for predicting IDR. Patients with an rhTSH-stimulated Tg greater than 2 ng/mL prior to RAIT were 3.75 times more likely (95% confidence interval, 1.61-8.72) to have an IDR than those with a lower rhTSH-stimulated Tg (≤2 ng/mL). CONCLUSIONS: Pre-RAIT TSH-stimulated Tg levels are a risk factor for IDR after RAIT.

A Case of Radioactive Iodine Uptake Found in Artificial Eye.

Radioactive iodine (RAI) therapy is widely used as an adjunctive treatment in patients with differentiated thyroid cancer. Although I has high avidity in the functioning thyroid, and in differentiated thyroid cancer lesions, physiological and nonspecific uptake of I in healthy or benign tissue may contribute to false-positive findings on an I scan. Here, we present an interesting image of RAI uptake in the eye region post-RAI treatment, which has been identified as tear contamination in the artificial eye.

Anaplastic Oligodendroglioma Found as an Incidental Photopenic Lesion on 18F-FP-CIT PET/CT Image.

F-FP-CIT PET is a useful modality for imaging dopamine transporters. It has excellent resolution compared with I-beta-CIT SPECT and is widely used clinically for the evaluation of Parkinson disease. In general, the main focus of F-FP-CIT PET imaging is the basal ganglia, and it is important to observe whether F-FP-CIT uptake is normal in the putamen and caudate nuclei. However, abnormal findings may be seen in other brain regions besides the basal ganglia. Here, we present a case of anaplastic oligodendroglioma, a high-grade tumor, which was found as an incidental photopenic lesion on F-FP-CIT PET/CT.

Relation between tumor FDG uptake and hematologic prognostic indicators in stage I lung cancer patients following curative resection.

Hematologic parameters of systemic inflammation are receiving attention as promising prognostic indicators in cancer patients. Here, we investigated the relation and compared the prognostic values of circulating blood cell-based parameters and tumor F-fluoro-2-deoxyglucose (FDG) uptake in patients with stage I nonsmall cell lung cancers (NSCLC).Subjects were 1034 patients with newly diagnosed stage I NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) followed by curative resection. Total white blood cell (WBC) count, absolute neutrophil, lymphocyte and platelet counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were obtained. Tumor FDG uptake was measured as SUVmax.WBC, neutrophil and lymphocyte counts, and NLR demonstrated weak but significant correlation to tumor SUVmax. Using the upper quartile as cutoff, patients with high tumor SUVmax had significantly higher WBC, neutrophil and lymphocyte counts, and greater NLR. There were 144 recurrences (13.9%) over a median follow-up of 29.5 months. On Cox proportional hazards regression analysis, WBC count, tumor SUVmax, age, gender, smoking, cell type, and tumor stage were significant univariate prognostic factors. On multivariate analysis, high tumor SUVmax (HR = 2.22; 95% CI, 1.52-3.25; P < 0.001), tumor stage 1B (HR = 2.11; 95% CI, 1.47-3.01; P < 0.001), and old age (HR = 1.03; 95% CI, 1.01-1.05; P = 0.002) were significant independent predictors of poor survival. Finally, high tumor SUVmax remained a significant predictor of prognosis in both low and WBC count groups.Circulating blood counts showed significant correlation to tumor FDG uptake in early stage NSCLC. WBC count was a significant univariate variable, but tumor FDG uptake was a superior and independent predictor of outcome. Hence, tumor FDG uptake effectively stratified prognosis in patients with low as well as high WBC count.

The Clinical Role of Dual-Time-Point (18)F-FDG PET/CT in Differential Diagnosis of the Thyroid Incidentaloma.

Thyroid incidentalomas are common findings during imaging studies including (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) for cancer evaluation. Although the overall incidence of incidental thyroid uptake detected on PET imaging is low, clinical attention should be warranted owing to the high incidence of harboring primary thyroid malignancy. We retrospectively reviewed 2,368 dual-time-point (18)F-FDG PET/CT cases that were undertaken for cancer evaluation from November 2007 to February 2009, to determine the clinical impact of dual-time-point imaging in the differential diagnosis of thyroid incidentalomas. Focal thyroid uptake was identified in 64 PET cases and final diagnosis was clarified with cytology/histology in a total of 27 patients with (18)F-FDG-avid incidental thyroid lesion. The maximum standardized uptake value (SUVmax) of the initial image (SUV1) and SUVmax of the delayed image (SUV2) were determined, and the retention index (RI) was calculated by dividing the difference between SUV2 and SUV1 by SUV1 (i.e., RI = [SUV2 - SUV1]/SUV1 × 100). These indices were compared between patient groups that were proven to have pathologically benign or malignant thyroid lesions. There was no statistically significant difference in SUV1 between benign and malignant lesions. SUV2 and RI of the malignant lesions were significantly higher than the benign lesions. The areas under the ROC curves showed that SUV2 and RI have the ability to discriminate between benign and malignant thyroid lesions. The predictability of dual-time-point PET parameters for thyroid malignancy was assessed by ROC curve analyses. When SUV2 of 3.9 was used as cut-off threshold, malignancy on the pathology could be predicted with a sensitivity of 87.5 % and specificity of 75 %. A thyroid lesion that shows RI greater than 12.5 % could be expected to be malignant (sensitivity 88.9 %, specificity 66.3 %). All malignant lesions showed an increase in SUVmax on the delayed images compared with the initial images. But in the group of benign lesions, 37.5 % (6/16) showed a decrease or no change in SUVmax. Dual-time-point (18)F-FDG PET/CT, obtaining additional images 2 h after injection, seems to be a complementary method for the differentiation between malignancy and benignity of incidental thyroid lesions.

Peripheral bone involvement of intravascular large B-cell lymphoma on 99mTc-MDP bone scan and 18F-FDG PET/CT.

A 64-year-old man was admitted for evaluation of recently developed anemia and bone pain. The bone scan showed diffusely active lesions in the peripheral bones, symmetrically. Interestingly, 18F-FDG PET/CT revealed the hypermetabolic changes in the peripheral bones as well as the internal organs. Biopsy of bone marrow confirmed the diagnosis of intravascular B-cell lymphoma. After the 3 cycles of R-CHOP chemotherapy, 18F-FDG PET/CT showed improvement of the previous hypermetabolic lesions, suggesting good response. Intravascular B-cell lymphoma is a rare and aggressive variant of diffuse large cell lymphoma characterized by proliferation of malignant cells within the vascular lumina.

Detectability of T-Measurable Diseases in Advanced Gastric Cancer on FDG PET-CT.

PURPOSE: Usefulness of FDG PET-CT in monitoring response in locally advanced gastric cancer has been reported. The purpose of this study was to evaluate the related factors to detect measurable diseases in advanced gastric cancer on FDG PET-CT. METHODS: We retrospectively reviewed 38 patients diagnosed as having advanced gastric cancer. We defined the measurable diseases when there was visualized tumor of which maximum standardized uptake value (SUVmax) was higher than 1.35*SUVmax of liver + 2*SD of liver SUV. We evaluated what kinds of factors from the clinicopathologic features were related to identifying measurable diseases. RESULTS: Of 38 patients with advanced gastric cancer, 18 (50 %) had measurable tumors on FDG PET-CT. Measurable tumors were significantly more frequent in well or moderately differentiated adenocarcinoma (70.5 % vs 35.3 %, p < 0.05), in the tumors located at antrum or angle (66.7 % vs 29.4 %, p < 0.05) and in the elderly group (age of 55 years old or more, 72.0 % vs 8.3 %, p < 0.001) than the others, respectively. By multivariate analysis, age at diagnosis was the only independent predictor for the measurable disease on FDG PET-CT. CONCLUSION: We found that age at diagnosis, as well as histologic types and location of tumors, were the affecting factors to detect measurable disease on FDG PET-CT in patients with advanced gastric cancer. Our study suggests that elderly patients of age of 55 years old or more can frequently have T-measurable disease on FDG PET-CT in advanced gastric cancer and FDG PET-CT will be helpful to monitor measurable disease.

Topical ALA-Photodynamic Therapy for Acne Can Induce Apoptosis of Sebocytes and Down-regulate Their TLR-2 and TLR-4 Expression.

BACKGROUND: Although photodynamic therapy (PDT) is widely performed for acne, little is known about its exact therapeutic mechanism. OBJECTIVE: We aimed to estimate the efficacy and safety of PDT on acne and to discover its mode of action. METHODS: We performed PDT on 12 patients with mild to moderate acne. The clinical efficacy was assessed by counting the acne lesions and measuring the sebum secretion before and after PDT. In addition, we took biopsy samples from the peri-lesional areas before and after 3-session of PDT. To examine the degree of apoptosis of the sebaceous follicles, TUNEL assay was performed. To investigate the changes of toll-like receptor (TLR)-2 and TLR-4 expression after PDT, immunohistochemical stainings were also carried out. Finally, we performed TUNEL assay using the cultured sebocytes to confirm the apoptosis of sebocytes in vitro after PDT. RESULTS: There was a significant reduction in the number of inflammatory acne lesions after PDT, compared to baseline (p<0.05). Sebum excretion significantly decreased 2 weeks after the first PDT session except for one patient (p<0.05). The TUNEL positive cells in the peri-lesional sebaceous glands after PDT markedly increased, compared with those of before PDT. A decrease in TLR-2 and TLR-4 expression by sebaceous glands and epidermis after PDT was 50% and 30%, respectively. CONCLUSION: Our results demonstrate that apoptosis of the sebaceous glands is associated with improvement of acne by PDT. PDT has shown to down-regulate TLR-2 and TLR-4 expression in the sebaceous glands and epidermis of acne patients.

Radiation safety issues in y-90 microsphere selective hepatic radioembolization therapy: possible radiation exposure from the patients.

PURPOSE: The purpose of this study was to estimate the possible external radiation dose to other individuals from patients treated with Y-90 resin microspheres for unresectable hepatocellular carcinoma. METHODS: We designed the study prospectively to estimate the possible radiation dose to other individuals from patients who had been treated with Y-90 microspheres for unresectable hepatocellular carcinoma. We estimated the total effective dose equivalent (TEDE) using two methods: 'theoretical' TEDEs according to the administered activity and 'measured' TEDE based on the 'measured' ambient radiation exposure rate. We compared the results from each method to determine when we can release patients from confinement at the earliest time complying with the patient release criteria. RESULTS: A total of 20 administrations of Y-90 resin microspheres were done in 18 patients. The average administered activity was 1.2 ± 0.77 (0.28-2.97) GBq. The 'theoretical' TEDEs were in the range of 0.8-10 µSv. The 'measured' TEDEs were in the range of 2.31-185 µSv. The measured TEDEs tend to be higher than the theoretical TEDEs. The values of theoretical and measured TEDE were both far less than 1 mSv, the upper limit at which the licensee can release a patient without any written documents. CONCLUSION: The effective dose equivalent caused by the Y-90 microsphere administered patient is very low. It is safe in terms of radiation safety to the other individuals when Y-90 microsphere radioembolization therapy is done with dose less than 3 GBq. Because the measured TEDE tends to be higher than the theoretical TEDE, it is recommended to use 'measured' TEDE for determining patient release.

Late-onset eccrine angiomatous hamartoma on the forehead.

A 71-year-old Korean man presented with a solitary erythematous plaque on his forehead (Fig. 1). It was first noticed by the patient 1 year previously and had slowly increased in size over that time. Physical examination revealed a slightly elevated, 1.5 cm x 1.5 cm erythematous plaque on the upper midline of the forehead. Sweating was not evoked by physical work or emotional stress. There was no pain or tenderness associated with the lesion. The patient had no history of trauma to the forehead. Histopathologic examination of the lesion showed increased numbers of eccrine glands, as well as dilated vascular channels in the deep dermis and subcutaneous tissue (Fig. 2). An immunohistochemical study showed that these eccrine glands stained positively for S-100 and carcinoembryonic antigen (CEA), and the vascular channels for the antifactor VIII-related antigens. These findings are consistent with eccrine angiomatous hamartoma. There was no change in the lesion during the 1-year follow-up period.

Treatment of congenital nevomelanocytic nevi with the CO2 and Q-switched alexandrite lasers.

BACKGROUND: A variety of treatment options exist for the management of congenital nevomelanocytic nevi (CNN). Surgical treatment has been the traditional approach, but scarring and cosmetic problems are common. Recently, lasers have been used to treat CNN because, in some cases, surgical excisions are inadequate owing to their inaccessible location, size, and depth. OBJECTIVE: The effects of the combined use of CO2 laser and Q-switched Alexandrite laser on CNN were evaluated. METHODS: Eleven patients with CNN were enrolled in this study. The surface epithelium was abraded by a CO2 laser. Subsequently, the lesion was treated by a Q-switched alexandrite laser. Repeated treatments were done every 6 weeks. The results were evaluated clinically by both physicians and patients at 2 and 6 weeks after each treatment using a 5-point grade scale. RESULTS: By the end of the treatments, the average improvement scale assessed by the physicians, with a 5-point grade scale, was 3.82 and that of the patients was 3.73. There were no cases of hypertrophic scar or postinflammatory hyperpigmentaton persisting beyond 2 weeks. There were no recurrences during the 2-year follow-up period. CONCLUSION: The combined laser treatment is an effective method for the treatment of CNN. The clinical outcome was favorable; the treatment was safer, less painful, and relatively nonscarring; and there was a quicker recovery period and less of a burden to repeat treatment when necessary compared with conventional treatments.