Validation of Biomechanical Computed Tomography for Fracture Risk Classification in Metastatic Hormone-sensitive Prostate Cancer.

BACKGROUND: Guidelines recommend dual-energy x-ray absorptiometry (DXA) screening to assess fracture risk and benefit from antiresorptive therapy in men with metastatic hormone-sensitive prostate cancer (mHSPC) on androgen deprivation therapy (ADT). However, <30% of eligible patients undergo DXA screening. Biomechanical computed tomography (BCT) is a radiomic technique that measures bone mineral density (BMD) and bone strength from computed tomography (CT) scans. OBJECTIVE: To evaluate the (1) correlations between BCT- and DXA-assessed BMD, and (2) associations between BCT-assessed metrics and subsequent fracture. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective cohort study was conducted among patients with mHSPC between 2013 and 2020 who received CT abdomen/pelvis or positron emission tomography/CT within 48 wk before ADT initiation and during follow-up (48-96 wk after ADT initiation). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used univariate logistic regression to assess the associations between BCT measurements and the primary outcomes of subsequent pathologic and nonpathologic fractures. RESULTS AND LIMITATIONS: Among 91 eligible patients, the median ([interquartile range) age was 67 yr (62-75), 44 (48.4%) were White, and 41 (45.1%) were Black. During the median follow-up of 82 wk, 17 men (18.6%) developed a pathologic and 15 (16.5%) a nonpathologic fracture. BCT- and DXA-assessed femoral-neck BMD T scores were strongly correlated (R2 = 0.93). On baseline CT, lower BCT-assessed BMD (odds ratio [OR] 1.80, 95% confidence interval or CI [1.10, 3.25], p = 0.03) was associated with an increased risk of a pathologic fracture. Lower femoral strength (OR 1.63, 95% CI [0.99, 2.71], p = 0.06) was marginally associated with an increased risk of a pathologic fracture. Neither BMD (OR 1.52, 95% CI [0.95, 2.63], p = 0.11) nor strength (OR 1.14, 95% CI [0.75, 1.80], p = 0.57) was associated with a nonpathologic fracture. BCT identified nine (9.9%) men eligible for antiresorptive therapy, of whom four (44%) were not treated. Limitations include low fracture numbers resulting in lower power to detect fracture associations. CONCLUSIONS: Among men diagnosed with mHSPC, BCT assessments were strongly correlated with DXA, predicted subsequent pathologic fracture, and identified additional men indicated for antiresorptive therapy. PATIENT SUMMARY: We assess whether biomechanical computer tomography (BCT) from routine computer tomography (CT) scans can identify fracture risk among patients recently diagnosed with metastatic prostate cancer. We find that BCT and dual-energy x-ray absorptiometry-derived bone mineral density are strongly correlated and that BCT accurately identifies the risk for future fracture. BCT may enable broader fracture risk assessment and facilitate timely interventions to reduce fracture risk in metastatic prostate cancer patients.

Heterozygous variant in WNT1 gene in two brothers with early onset osteoporosis.

Osteoporosis is a multifactorial disorder characterized by low bone mass and strength, leading to increased risk of fracture. The WNT pathway plays a critical role in bone remodeling by enhancing osteoblastic differentiation, which promotes bone formation, and inhibiting osteoclastic differentiation, decreasing bone resorption. Therefore, genetic alterations of this pathway will lead to impaired bone homeostasis and could contribute to varying response to treatment. We present the case of two brothers with early osteoporosis who were found to have a heterozygous variant of unknown significance in the WNT1 gene, c.1060_1061delCAinsG (p.H354Afs*39). This finding demonstrates that frameshift variants in WNT1 may also act in a dominant fashion leading to decreased bone mass.

A highly conductive thin film composite based on silver nanoparticles and malic acid for selective electrochemical sensing of trichloroacetic acid.

A highly conductive thin film composite based on silver nanoparticles (AgNPs) and malic acid (MA) was deposited on glassy carbon electrode (GCE) for the selective and sensitive electrochemical sensing of trichloroacetic acid (TCA). The casting solution containing MA functionalized AgNPs was employed as a precursor for the thermal deposition of the AgNPs integrated MA thin film composite onto the GCE surface. The uniform coverage of AgNPs within the thin film composite at GCE was obtained by field emission scanning electron microscopy (FESEM). A significantly high charge transfer resistance of the modified electrode (85.7â€¯Ω for AgNPs-MA/GCE in 2 mM [Fe(CN)6]3-/4- at a bias of +0.235 V as compared to bare GCE (38.01 Ω) verified the optimum coating of AgNPs-MA composite at the surface of the electrode. The AgNPs-MA composite deposited GCE revealed substantial electrocatalytic activity toward TCA reduction with significantly enhanced reduction current. The novel electrode manifested a linear square wave voltammetric (SWV) response over the concentration ranges of 0.1-2 (R2 = 0.9953) and 4-100 µM (R2 = 0.9969) with a limit of detection (LOD) and limit of quantification (LOQ) of 30 nM and 92.5 nM, respectively. The modified electrode exhibited an excellent long-term stability (30 days) with the retention of >95% of initial current. The selectivity of the proposed electrode for the determination of TCA was examined in the presence of dichloroacetic acid (DCA) and monochloroacetic acid (MCA) with the retention of high recovery percentages.

Gestational Gigantomastia Complicated by PTHrP-Mediated Hypercalcemia.

Context: Gestational gigantomastia is an uncommon condition characterized by abnormal and excessive growth of breast tissue during an otherwise uncomplicated pregnancy. Gestational gigantomastia may be accompanied by hypercalcemia, which in some cases has been associated with elevated serum levels of PTHrP. The source of the PTHrP in these cases has been suggested to be the enlarged breasts. Objective: To describe the rapid resolution of hypercalcemia and normalization of serum PTHrP after elective termination of pregnancy, indicating that the placenta was the source of the PTHrP. Design: A retrospective analysis of clinical and biochemical data over a 2-year interval and review of literature. Setting: An academic medical center. Patient: A 33-year-old G8P4 female who presented at week 8 of pregnancy with gestational gigantomastia and subsequently developed marked hypercalcemia at week 13. Serum levels of PTH were suppressed but circulating PTHrP was elevated. There was no history of hypercalcemia or significant breast growth during previous pregnancies. Intervention: Hypercalcemia was poorly responsive to IV saline, prednisone, calcitonin, and cinacalcet. She requested termination of pregnancy at week 20. Results: Serum levels of calcium, PTH, and PTHrP normalized within 48 hours of termination of pregnancy. Conclusion: The rapid resolution of hypercalcemia after termination of pregnancy, despite persistent gigantomastia, provides evidence for a pathologic role of the placenta in the excess production of PTHrP, possibly through an as yet uncharacterized placenta-breast hormonal axis.

The impact of thyroid nodule size on the risk of malignancy in follicular neoplasms.

BACKGROUND/AIM: Studies have shown that the risk of malignancy in follicular neoplasms is as high as 30%. Often, surgery is recommended for such lesions, not for therapeutic purposes but as a diagnostic method, leading to increased hospital costs and related morbidities. Recent studies have suggested that tumor size predicts malignant potential of these follicular neoplasms. Our aim was to identify the impact of nodule size on the risk of malignancy for such lesions. PATIENTS AND METHODS: A retrospective medical chart review was undertaken for patients who underwent thyroid surgery at a single academic North American Institution. A total of 120 follicular lesions, follicular neoplasms (Bethesda category IV) or follicular lesions of undetermined significance (Bethesda category III) in 110 patients undergoing thyroid surgery were evaluated. Nodule size as measured by ultrasound, fine-needle aspiration cytological results, and final histopathology reports were reviewed. Analysis was performed by classification according to nodule size: <3 cm, ≥3 cm, <4 cm and ≥4 cm. RESULTS: Out of the 120 nodules, 48 (40%) were reported to be malignant on final pathological examination. The malignancy rate in nodules<3 cm and ≥ 3cm was 41% and 37.8%, respectively (p=0.84). When 4 cm was used as the cut-off, the rate in nodules<4 cm and ≥4 cm was 40.6% and 37.5%, respectively (p=0.82). CONCLUSION: Increased thyroid nodule size does not increase the malignancy rate for follicular neoplasms. Hence, we recommend against routine total thyroidectomy for patients with follicular neoplasms based on the size criteria.

Thyroid cancer in black thyroid glands: the effect of age and race.

BACKGROUND: Black thyroid pigmentation is a rare entity. The risk of malignancy is higher in black thyroid compared to non-black thyroid glands. We aimed to examine the effect of age and race on the risk of malignancy in black thyroid glands. METHODS: We identified a series of consecutive patients who underwent thyroidectomy at an academic institution between January 1998 and May 2013. Patient demographics, clinical characteristics, and histopathology data were reviewed. RESULTS: Among 925 patients who underwent thyroidectomy, 112 (12.1%) patients with black thyroid glands were identified. The incidence of thyroid cancer was 55.4% in black thyroid glands compared to 32.8% in non-black thyroid glands (p < 0.0001). The incidence of papillary thyroid cancer among the black and non-black thyroid glands was 34.8 and 20%, respectively (p < 0.001). The mean age (± SD) for patients with black thyroid glands and those with non-black thyroid was 54.3 ± 12.8 and 51.2 ± 15.7 years, respectively (p = 0.05). Black thyroid glands were also associated with a higher incidence of microcarcinomas (76 vs. 59%, p = 0.02). Among patients with black thyroid glands, Caucasians had a higher malignancy rate (63.4%) than African-Americans (37%; p = 0.03). CONCLUSION: The incidence of malignancy is higher in black thyroid compared to non-black thyroid glands, specifically in Caucasians.

Crystal structure of ethyl 2-[(4-bromo-phen-yl)amino]-3,4-di-methyl-pent-3-enoate.

In the title compound, C15H20BrNO2, there are two independent mol-ecules (A and B) comprising the asymmetric unit and these adopt very similar conformations. In A, the dihedral angle between the CO2 and MeC=CMe2 groups is 80.7 (3)°, and these make dihedral angles of 3.5 (3) and 84.09 (16)°, respectively, with the bromo-benzene ring. The equivalent dihedral angles for mol-ecule B are 78.4 (3), 2.1 (3) and 78.37 (12)°, respectively. The most prominent inter-actions in the crystal packing are amine-N-H⋯O(carbon-yl) hydrogen bonds between the two independent mol-ecules, resulting in non-centrosymmetric ten-membered {⋯OC2NH}2 synthons. Statistical disorder is noted for each of the terminal methyl groups of the ethyl residues.

Adherence and efficacy of screening for low bone mineral density among ulcerative colitis patients treated with corticosteroids.

OBJECTIVES: Ulcerative colitis (UC) is associated with an increased risk of metabolic bone disease and fragility fractures. The aim of this study was to assess the adherence to the guidelines issued by the American Gastroenterology Association (AGA) for the screening for low bone density in UC patients and to assess the benefits of dual-energy X-ray absorptiometry (DXA) screening among corticosteroid (CS)-treated UC patients. METHODS: Nationwide Veterans Affairs system (VA) data were obtained. UC patients followed up in the VA between 2001 and 2011 and the occurrence of fragility fractures were identified using International Classification of Diseases, Ninth Revision codes. Exposure to CSs was assessed using pharmacy data. DXA screening was assessed using the VA procedure database. Post DXA screening, medication use was also assessed from the pharmacy database. Cox regression analysis was performed to calculate the hazard ratio (HR) of fragility fractures among those patients who received DXA compared with those who did not. RESULTS: We included 5,736 patients. Among them, 80 (1.4%) patients suffered from fragility fractures during the follow-up period. Overall adherence rate to AGA guidelines was 23%. Adherence rate was highest among postmenopausal women (48%) and lowest among men above 50 years of age (20%). UC patients who received DXA screening were more likely to be started on bisfosfonates (P<0.001), calcitonin (P<0.001), vitamin D, and calcium (P<0.001) compared with those who did not receive screening. Those who received DXA screening were half as likely (HR=0.5, 0.3-0.9, P=0.03) to develop fragility fractures as compared with those who did not receive screening. The benefits were more prominent among those with higher CS exposure. CONCLUSIONS: Rates of DXA screening were low among CS-treated UC patients. Those who received DXA screening were more likely to be started on antiresorptive therapy and supplemental medications and had a 50% reduction in the risk of fragility fractures. More efforts should be directed toward raising the adherence to AGA guidelines and the awareness of DXA benefits.

Acidosis: the prime determinant of depressed sensorium in diabetic ketoacidosis.

OBJECTIVE: The etiology of altered sensorium in diabetic ketoacidosis (DKA) remains unclear. Therefore, we sought to determine the origin of depressed consciousness in DKA. RESEARCH DESIGN AND METHODS: We analyzed retrospectively clinical and biochemical data of DKA patients admitted in a community teaching hospital. RESULTS: We recorded 216 cases, 21% of which occurred in subjects with type 2 diabetes. Mean serum osmolality and pH were 304 +/- 31.6 mOsm/kg and 7.14 +/- 0.15, respectively. Acidosis emerged as the prime determinant of altered sensorium, but hyperosmolarity played a synergistic role in patients with severe acidosis to precipitate depressed sensorium (odds ratio 2.87). Combination of severe acidosis and hyperosmolarity predicted altered consciousness with 61% sensitivity and 87% specificity. Mortality occurred in 0.9% of the cases. CONCLUSIONS: Acidosis was independently associated with altered sensorium, but hyperosmolarity and serum "ketone" levels were not. Combination of hyperosmolarity and acidosis predicted altered sensorium with good sensitivity and specificity.

Composite pheochromocytoma-ganglioneuroma: a rare experiment of nature.

OBJECTIVE: To present a rare case of composite pheochromocytoma-ganglioneuroma (Pheo-GN) of the adrenal medulla, review the related literature, and discuss the clinical features, pathologic findings, behavior, and management of such tumors. METHODS: A case report of a patient with composite Pheo-GN of the adrenal gland is presented. Using the online database PUBMED, we searched and analyzed all cases of composite pheochromocytoma reported in the English-language literature during the past 70 years. RESULTS: On computed tomography, a 61-year-old man was incidentally found to have a 3.8-cm nonadenomatous right adrenal lesion. Adrenalectomy revealed a 5-cm mass consistent with composite Pheo-GN. To date, 45 cases of composite pheochromocytomas have been reported during the past 70 years, 71% of which coexisted with ganglioneuromas. These tumors occurred with approximately equal frequency in male and female patients, the majority of whom were from 40 to 60 years old. Only 14 cases have been reported in the United States. Bilateral tumors were found in 3 cases. The mean size was 4 to 6 cm. Preoperatively, functional evidence was found in 76.3% of all composite pheochromocytomas (and in 67% of Pheo-GN). Only one Pheo-GN was found to have liver metastatic lesions at the time of autopsy; the rest were not aggressive. CONCLUSION: To our knowledge, this is the first literature review describing the characteristics and behavior of all reported cases of composite pheochromocytomas, with an emphasis on those with ganglioneuromas. Composite pheochromocytoma is a rare variant of a relatively uncommon disease diagnosed by pathologists only. Fortunately, the treatment of such an entity remains the same as for any pheochromocytoma.

Genetic networks controlling retinal injury.

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury. METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases. RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription factors. Three genomic loci control transcript expression of acute phase genes in brains of BXD RI mouse strains. One locus was identified on chromosome 12 and was highly correlated with the expression of classic acute phase genes. Within the locus we identified the inhibitor of DNA binding 2 (Id2) as a candidate upstream regulator. Id2 was upregulated as an acute phase transcript in injury models of rat retina, brain, and spinal cord. CONCLUSIONS: We defined a group of transcriptional changes associated with the retinal acute injury response. Using genetic linkage analysis of natural transcript variation, we identified regulatory loci and candidate regulators that control transcript levels of acute phase genes.