Development of the International Classification of Diseases Ontology (ICDO) and its application for COVID-19 diagnostic data analysis.

BACKGROUND: The 10th and 9th revisions of the International Statistical Classification of Diseases and Related Health Problems (ICD10 and ICD9) have been adopted worldwide as a well-recognized norm to share codes for diseases, signs and symptoms, abnormal findings, etc. The international Consortium for Clinical Characterization of COVID-19 by EHR (4CE) website stores diagnosis COVID-19 disease data using ICD10 and ICD9 codes. However, the ICD systems are difficult to decode due to their many shortcomings, which can be addressed using ontology. METHODS: An ICD ontology (ICDO) was developed to logically and scientifically represent ICD terms and their relations among different ICD terms. ICDO is also aligned with the Basic Formal Ontology (BFO) and reuses terms from existing ontologies. As a use case, the ICD10 and ICD9 diagnosis data from the 4CE website were extracted, mapped to ICDO, and analyzed using ICDO. RESULTS: We have developed the ICDO to ontologize the ICD terms and relations. Different from existing disease ontologies, all ICD diseases in ICDO are defined as disease processes to describe their occurrence with other properties. The ICDO decomposes each disease term into different components, including anatomic entities, process profiles, etiological causes, output phenotype, etc. Over 900 ICD terms have been represented in ICDO. Many ICDO terms are presented in both English and Chinese. The ICD10/ICD9-based diagnosis data of over 27,000 COVID-19 patients from 5 countries were extracted from the 4CE. A total of 917 COVID-19-related disease codes, each of which were associated with 1 or more cases in the 4CE dataset, were mapped to ICDO and further analyzed using the ICDO logical annotations. Our study showed that COVID-19 targeted multiple systems and organs such as the lung, heart, and kidney. Different acute and chronic kidney phenotypes were identified. Some kidney diseases appeared to result from other diseases, such as diabetes. Some of the findings could only be easily found using ICDO instead of ICD9/10. CONCLUSIONS: ICDO was developed to ontologize ICD10/10 codes and applied to study COVID-19 patient diagnosis data. Our findings showed that ICDO provides a semantic platform for more accurate detection of disease profiles.

Oncolytic herpesvirus therapy for mesothelioma - A phase I/IIa trial of intrapleural administration of HSV1716.

OBJECTIVES: Malignant Pleural Mesothelioma (MPM) remains a major oncological challenge with limited therapeutic options. HSV1716 is a replication restricted oncolytic herpes simplex virus with anti-tumor effects in multiple cell lines including MPM. Intrapleural treatment appeals because MPM is typically multifocal but confined to the pleura, and distant metastases are uncommon. We assessed the safety and possible efficacy of intrapleural HSV1716 for inoperable MPM. MATERIALS AND METHODS: Patients with MPM received 1 × 107iu HSV1716 injected via an indwelling intrapleural catheter (IPC) on one, two or four occasions a week apart. The primary endpoint was the safety and tolerability of HSV1716. Secondary endpoints were assessment of HSV1716 replication, detection of immune response and evaluation of tumor response. RESULTS: Of thirteen patients enrolled, five had received previous pemetrexed-cisplatin chemotherapy, and eight were chemotherapy naïve. Three patients were enrolled to receive one dose, three patients to two doses and seven patients to four doses. The treatment was well-tolerated with few virus-related adverse events and no dose limiting toxicities. Twelve patients were evaluable for response, as one patient withdrew early after a catheter fracture. There was evidence of viral replication/persistence in pleural fluid in seven of the twelve patients. Induction of Th1 cytokine responses to HSV1716 treatment occurred in eight patients and four patients developed novel anti-tumor IgG. No objective responses were observed but disease stabilization was reported in 50 % of patients at 8 weeks. CONCLUSIONS: Intrapleural HSV1716 was well-tolerated and demonstrated an anti-tumor immune response in MPM patients. These results provide a rationale for further studies with this agent in MPM and in combination with other therapies.

Giant berry aneurysms in a forensic setting: a series of 14 cases.

This is a series reviewing 14 cases of giant saccular aneurysms diagnosed at the Office of the Chief Medical Examiner of New York City collected over an 11-year period. Data collected on all 14 cases included neuropathological findings, comorbidities, and toxicological findings. Of these 14 cases, 8 were in women, and the ages ranged from 3 to 79 years, with a mean and a median of 50 years. Women were overrepresented in the sixth through eighth decades. Of the 14 cases described, 11 presented with a subarachnoid hemorrhage; 3, no hemorrhage; 2, subdural hemorrhage; 8, intraventricular hemorrhage; 2, intracerebral hemorrhage; and 8, more than 1 hemorrhage type. Location of the aneurysms varied with 6 in the left side of the brain, 6 present in the right side of the brain, and 2 at the midline. We described the clinical, pathological, and toxicological findings associated with these giant aneurysms.