Purpose Distinguishing between benign granulmoas and adenocarcinomas is confounded by their similar visual appearance on routine CT scans. Unfortunately, owing to the inability to discriminate these lesions radigraphically, many patients with benign granulomas are subjected to unnecessary surgical wedge resections and biopsies for pathologic confirmation of cancer presence or absence. This suggests the need for improved computerized characterization of these nodules in order to distinguish between these two classes of lesions on CT scans. While there has been substantial interest in the use of textural analysis for radiomic characterization of lung nodules, relatively less work has been done in shape based characterization of lung nodules, particularly with respect to granulmoas and adenocarcinomas. The primary goal of this study is to evaluate the role of 3D shape features for discrimination of benign granulomas from malignant adenocarcinomas on lung CT images. Towards this end we present an integrated framework for segmentation, feature characterization and classification of these nodules on CT. Methods The nodule segmentation method starts with separation of lung regions from the surrounding lung anatomy. Next, the lung CT scans are projected into and represented in a three dimensional spectral embedding (SE) space, allowing for better determination of the boundaries of the nodule. This then enables the application of a gradient vector flow active contour (SEGvAC) model for nodule boundary extraction. A set of 24 shape features from both 2D slices and 3D surface of the segmented nodules are extracted, including features pertaining to the angularity, spiculation, elongation and nodule compactness. A feature selection scheme, PCA-VIP, is employed to identify the most discriminating set of features to distinguish granulmoas from adenocarcinomas within a learning set of 82 patients. The features thus identified were then combined with a support vector machine classifier and independently validated on a distinct test set comprising 67 patients. The performance of the classifier for both of the training and validation cohorts was evaluated by the area under receiver characteristic curve (ROC). Results We used 82 and 67 studies from two different institutions respectively for training and independent validation of the model and the shape features. The Dice coefficient between automatically segmented nodules by SEGvAC and the manual delineations by expert radiologists (readers) was 0.84 ± 0.04 whereas inter-reader segmentation agreement was 0.79 ± 0.12. We also identified a set of consistent features (Roughness, Convexity and Spherecity) that were found to be strongly correlated across both manual and automated nodule segmentations (R > 0.80, p < 0.0001) and capture the marginal smoothness and 3D compactness of the nodules. On the independent validation set of 67 studies our classifier yielded a ROC AUC of 0.72 and 0.64 for manually- and automatically segmented nodules respectively. On a subset of 20 studies, th...

Objective To determine the association between vitamin D status and morbidity and mortality in adult hospitalized COVID-19 patients Methods We performed a retrospective chart review study in COVID-19 patients aged ≥18 years old hospitalized at Boston University Medical Center between March 1 – August 4, 2020. All studied patients were tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D results measured within one year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and were analyzed to determine the association between vitamin D status and hospital morbidity and mortality. Results Among the 287 patients, 100 (36%) patients were vitamin D-sufficient [25(OH)D >30 ng/mL] and 41 (14%) patients died during the hospitalization. Multivariate analysis in patients aged ≥65 years old revealed that vitamin D sufficiency [25(OH)D ≥30 ng/mL] was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95%CI, 0.12–0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95%CI, 0.05–0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95%CI, 0.08–0.88), after adjustement for potential confounders. Among patients with body mass index <30 kg/m 2 , vitamin D sufficiency was statistically significantly associated with a decreased odds of death (adjusted OR 0.18, 95%CI, 0.04–0.84). No significant association was found in the subgroups of patients aged <65 years old or BMI ≥30 kg/m 2 . Conclusion We revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.

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Introduction: Bone metastases from differentiated thyroid cancer are generally resistant to radioactive iodine (RAI) therapy and are associated with poor prognosis, except for RAI-avid bone metastases with no structural correlate on imaging studies. Case: A 59 y/o woman presented for the evaluation of non-toxic multinodular goiter. Thyroid US showed a 2.7 cm nodule meeting FNAB criteria and no suspicious cervical lymph nodes. Cytology reported a Bethesda IV category with ThyroSeq V3 positive for chromosomal copy number alterations and a high Na+/I− symporter (NIS) expression (27%) with an ~ 60% probability of cancer. The patient underwent left lobectomy with isthmusectomy without neck dissection. Surgical pathology showed a 3.5 cm papillary thyroid carcinoma with extensive angioinvasion (≥4 vessels), negative margins, no ETE, and did not contain a BRAF V600E mutation. Completion thyroidectomy, in anticipation of RAI treatment, showed no additional tumor. Post-operative Tg after 6 weeks was unexpectedly high at 69 ng/mL (negative Tg Ab, TSH 5.7 uIU/ml) which prompted a rhTSH I-123 RAI WBS with SPECT/ CT and a diagnostic chest CT to uncover possible distant metastases. There was RAI uptake in the thyroid bed and right anterolateral 9thrib without a CT correlate (no osteolytic lesion) but with a signal abnormality on MRI. She was categorized as T2NxM1, 8th Edition AJCC Stage IVB, and ATA high risk. She was treated with 148.3 mCi I-131. Unfortunately, 6 months later the Tg was elevated and rising (Tg 38.4 ng/mL, negative Tg Ab, TSH 0.05 uIU/ml). A second diagnostic I-123 WBS with SPECT/ CT showed a new recurrence in the neck but no uptake in the rib lesion on planar images or other distant sites. Because of the unusually high Tg without any RAI-avid metastatic disease, an 18-FDG PET/CT was ordered to search for non-RAI avid disease. This showed disease confined to the neck and increased sclerosis of the rib lesion without increased FDG-uptake consistent with treated disease status post-RAI. There were no other distant hypermetabolic lesions. The left thyroid bed lesion was biopsied and consistent with Bethesda VI cytology and she will soon undergo left central neck dissection with tumor resection. Discussion: RAI-avid bone metastases without structural correlate on high-resolution imaging are a subtype of bone metastases located in the marrow. They do not present as the typical lytic lesions from cortical destruction. They often resolve following RAI treatment, do not cause skeletal-related complications, and do not significantly affect prognosis. The combination of high NIS expression and increased vascularity in the bone marrow (as opposed to the protected microenvironment in the bone cortex) makes them vulnerable to RAI treatment. Recognition of this subset of bone lesions may prevent overtreatment with high doses of RAI treatment and avoid the use of bisphosphonates or external beam radiation.

Introduction: Parathyroid carcinoma (PC) is a rare malignancy with a high rate of recurrence and metastasis. Case: A 63-year-old man with a 13-year history of recurrent PC requiring 5 operations, including parathyroidectomies, thyroidectomy, and neck dissections presented with polyuria, polydipsia, and worsening rib pain. He had been recently treated with 6 monthly octreotide injections and maximal dose cinacalcet for gradually rising Ca/PTH levels. Tests revealed serum Ca 13.1mg/dL (8-10.5mg/dL), PTH 1750pg/mL (11-90 pg/mL), and serum Cr 3.34mg/dL (0.5-1.3mg/dL). Imaging identified tumor in the right 6th rib (3.6cm lytic lesion), and soft tissue lesions in the left thyroid bed (3 masses, the largest 1.6cm) and the suprasternal notch (1.1cm). He underwent rib resection (metastasectomy) and PTH declined from 2334pg/mL to 671pg/mL. Although metastasectomy improved the PTH level, Ca levels began to rise from the residual tumor. A multidisciplinary team deemed the risk of complications from repeat neck surgery to be prohibitively high. Temozolomide (TEM) (150-200mg/m2/d x 5d, q28d) was instituted 3 months after the rib resection. 13 months later, PTH has stably ranged from 600-800 pg/mL with a normal serum Ca of 9.8mg/dL. Recent imaging shows stable disease in the neck, without distant disease. Discussion: The mainstay of therapy for initial and recurrent/metastatic PC is surgery. Inoperable disease has a poor prognosis because of lack of effective systemic therapies. Radiation and chemotherapy have not shown much efficacy. Results of treatment with octreotide have not been encouraging. Anti-PTH immunotherapy and Lutathera are promising but require further investigation. Usually, no targetable mutation is found. Anti-angiogenic TKI’s (sorafenib, lenvatinib) have been used with varying success. An exciting therapy used in this patient is TEM, an alkylating agent used for CNS tumors, neuroendocrine tumors (NET) and aggressive pituitary tumors. A previous report described successful use of TEM in a case of metastatic PC, whose tumor harbored high O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, a known predictor of positive response in CNS tumors. Promoter methylation is an epigenetic alteration that leads to low MGMT enzyme activity & enhances the cytotoxicity of TEM. Some studies in NET demonstrated tumor response irrespective of MGMT status. This leads to the question of whether the same is true in PC. Our patient has radiographic/biochemical stable disease on TEM, and a surprising retrospective discovery was that the MGMT promoter was unmethylated. This is a unique case of PC which seems to be responding to TEM despite absent promoter methylation. Further studies are warranted, as the incidence of PC is rising over the past decades. In the interim, clinicians could consider using TEM for in-operable PC irrespective of MGMT methylation status.