Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Cec and You Shall Find: Cecal Perforation in a Patient with COVID-19

Digestive Diseases and Sciences -     

Bone mineral density testing in healthy postmenopausal women. The role of clinical risk factor assessment in determining fracture risk.

The ease of measurement and the quantitative nature of bone mineral densitometry (BMD) is clinically appealing. Despite BMD's proven capability to stratify fracture risk, data indicate that clinical risk factors provide complementary information on fracture susceptibility that is independent of BMD. Methods to quantify fracture risk using both clinical and BMD variables would have great appeal for clinical decision-making. We describe a procedure for quantifying hip fracture risk (5-yr and remaining lifetime) based on (1) the individual's age alone (base model, assuming average clinical risk factors and bone density), (2) incorporation of multiple patient-specific clinical risk factor data in the base model, and (3) incorporation of both patient-specific clinical risk factor data and BMD results.     

Pulmonary resection for metastases from colorectal cancer

Aim: The prognosis of patients with disseminated colorectal carcinoma is poor except for those with single organ pulmonary or hepatic metastases. The objective of the present study was to evaluate the result of pulmonary metastasectomy for colorectal secondary and to identify the prognostic factors. Methods: This was a retrospective study of 80 patients who had pulmonary metastasectomy for pulmonary secondary from colorectal carcinoma in Queen Elizabeth Hospital, Hong Kong. Results: The overall 5‐year and 10‐year survival rates of the entire cohort were 42.5% and 35.5%, respectively. High premetastasectomy carcinoembryonic antigen (> 20 μg/dL), short disease‐free interval (< 12 months) and incomplete resection were the independent prognostic factors. Neither the characteristics of the primary colorectal tumour nor the number of metastatic nodules had a significant contribution to the long‐term survival. Six patients underwent second pulmonary metastasectomy and three were still free from tumour recurrence after the second operation. Conclusion: Patients with pulmonary metastases from colorectal carcinoma would benefit from pulmonary metastasectomy. High premetastasectomy carcinoembryonic antigen and short disease‐free interval were negative predictive factors for survival. Long‐term follow‐up study is required, as recurrence can occur more than 5 years after pulmonary metastasectomy. Also, whether the survival benefit is due to surgical treatment effect or lead‐time bias remains undecided.     

A mechanism for reducing intraocular pressure in normal volunteers using UF-021, a prostaglandin-related compound]

The mechanism of reduction of intraocular pressure (IOP) and other ocular effects were studies after topical application of prostaglandin (PG) F2 alpha and UF-021, a new PG related compound, in eight normal volunteers. IOP, aqueous humor flow rate and outflow rate were evaluated during a period of four hours after the application. Both PGF2 alpha and UF-021 caused significant and similar IOP reduction for four hours. Neither compound produced any significant change in the aqueous humor flow rate or outflow rate, suggesting the increase of unconventional outflow rate as being the possible mechanism of IOP reduction in normal human eyes.     

Effect of meropenem on fecal flora in children]

Meropenem (MEPM, SM-7338), a novel parenteral carbapenem antibiotic, was examined for its effect on intestinal flora in children. Seven children with infectious diseases (3 male and 4 female children of age's ranging from 4 months to 8 years and 9 months weighing from 7.3 to 23.0 kg) were treated with MEPM at doses ranging 10.3 to 40.5 mg/kg 3 or 4 times a day for 6 to 12 days. Before, during and after the treatment, identities and numbers of various bacteria contained in 1 g of feces were determined and fecal beta-lactamase activity and Clostridium difficile D-1 antigen were also assayed. Changes in fecal flora during MEPM treatment was somewhat different depending on cases. Regarding Enterobacteriaceae among aerobes, all of 7 cases exhibited moderate or pronounced reductions in Escherichia coli. Some of the cases exhibited the tendency to increase in Klebsiella oxytoca. Enterobacter cloacae and Citrobacter freundii. E. coli which was reduced during the treatment increased rapidly after the treatment in 5 out of 7 cases, and the initial bacterial counts were restored. Diverse strains were observed within the genus Enterococcus, while the overall bacterial counts of this genus exhibited the tendency to increase during the treatment. As a result, no significant change in total aerobe count was observed in any case except 1 case where Enterococcus count was somewhat reduced. Among anaerobes, major bacteria such as Bacteroides, Bifidobacterium, Eubacterium and Peptococcaceae exhibited tendencies to decrease in some cases during the antibiotic treatment. Two infants and 1 child exhibited significant decreases in total anaerobe counts. In most of the cases, such changes in major anaerobes were transient and bacterial counts recovered to their initial values rapidly after completion of the treatment. In no cases, glucose non-fermentative Gram-negative bacilli or fungus became predominant. Although C. difficile D-1 antigen was observed in 4 cases, its changes had no relationship with characteristics of feces. C. difficile was not detected in any of the cases. MEPM was detected in feces in 4 cases being treatment, in concentrations ranging from 0.35 to 66.0 micrograms/g. Fecal MEPM levels were very low except in 1 case in which beta-lactamase was negative. From these results, effects of MEPM on intestinal flora in children were relatively minor compared to other new beta-lactam drugs. However, a care should be taken to minimize diarrhea and bacterial turnover when a prolonged use of the antibiotic, was practiced because of potential significant effects on intestinal flora.     

Atypical sexual behavior during sleep

OBJECTIVE: This article reports a case series of atypical sexual behavior during sleep, which is often harmful to patients or bed partners. METHODS: Eleven subjects underwent clinical evaluation of complaints of sleep-related atypical sexual behavior. Complaints included violent masturbation, sexual assaults, and continuous (and loud) sexual vocalizations during sleep. One case was a medical-legal case. Sleep logs, clinical evaluations, sleep questionnaires, structured psychiatric interviews, polysomnography, actigraphy, home electroencephalographic monitoring during sleep, and clinical electroencephalographic monitoring while awake and asleep were used to determine clinical diagnoses. RESULTS: Atypical sexual behaviors during sleep were associated with feelings of guilt, shame, and depression. Because of these feelings, patients and bed partners often tolerated the abnormal behavior for long periods of time without seeking medical attention. The following pathologic sleep disorders were demonstrated on polysomnography: partial complex seizures, sleep-disordered breathing, stage 3 to 4 non-rapid eye movement (REM) sleep parasomnias, and REM sleep behavior disorder. These findings were concurrent with morning amnesia. CONCLUSIONS: The atypical behaviors were related to different syndromes despite the similarity of complaints from bed partners. In most cases the disturbing and often harmful symptoms were controlled when counseling was instituted and sleep disorders were treated. In some cases treatment of seizures or psychiatric disorders was also needed. Clonazepam with simultaneous psychotherapy was the most common successful treatment combination. The addition of antidepressant or antiepileptic medications was required in specific cases.     

Expression of interleukin-18 by nasopharyngeal carcinoma cells: a factor that possibly initiates the massive leukocyte infiltration

Interleukin-18 (IL-18) is a single-chain cytokine that is produced by various cells. With interleukin-12 (IL-12), it synergistically stimulates activated T cells and natural killer (NK) cells to produce interferon-gamma (IFN-gamma). Nasopharyngeal carcinoma (NPC) is the most common form of nasal and nasopharyngeal malignancy, and in NPC tumor tissues there is an intense leukocyte infiltration comprising predominantly T cells and macrophages. We previously showed an increased expression of IFN-gamma in the infiltrating T cells. To identify the cells that provide IL-12 and IL-18 for stimulating the expression of IFN-gamma in activated T cells, NPC cell lines CNE-2 and HK-1, as well as biopsies obtained from NPC and control individuals, were examined. CNE-2 and HK-1 cells were found to express messenger RNA encoding IL-18, but not IL-12. Secreted IL-18 was detected in the culture supernatant. Addition of a caspase-1 inhibitor decreased the secretion level, indicating that this IL-18 secretion was caspase-1 dependent. Moreover, the in vitro IL-18 production in NPC cell lines correlated with the NPC tumor cells in situ. NPC tumor cells in the biopsies produced IL-18, as detected by immunohistochemistry and immunofluorescent double staining. In contrast, IL-18 expression was not observed in the control biopsies. We suggest that IL-18 secreted by NPC tumor cells plays a role in initiating the leukocyte infiltration process. IL-18 stimulates T cells and NK cells to produce IFN-gamma, which consequently activates macrophages and other immune cells to secrete chemokines to start a leukocyte recruitment cascade.     

Adhesion contact dynamics of HepG2 cells on galactose-immobilized substrates

The specific recognition between asialoglycoprotein receptor and galactose ligand at cell-substrate interfaces has been shown to mediate hepatocyte adhesion and maintain liver specific functions of hepatocytes. Conventionally, the success of hepatocyte attachment on engineered tissue scaffold is inferred from the degree of two-dimensional cell spreading that is measured by transmitted light microscopy. However, the actual contact mechanics and adhesion strength of hepatocytes during two-dimensional cell spreading has not been elucidated due to lack of biophysical probe. In this study, a novel biophysical technique known as confocal reflectance interference contrast microscopy (C-RICM) in conjunction with phase contrast microscopy is utilized to probe the adhesion dynamics, contact mechanics and two-dimensional spreading kinetics of HepG2 cells on galactose immobilized and collagen gel coated substrates. C-RICM demonstrates that HepG2 cells form strong adhesion contacts with both galactose-immobilized surfaces and collagen gel coated substrates. Moreover, HepG2 cells maintain their compact shapes in the presence of asialoglycoprotein receptor-mediated recognition while they become exceedingly spread under integrin-mediated adhesion on collagen gel coated substrate. The initial rate of adhesion contact formation and the steady-state adhesion energy of HepG2 cell population are highest on substrate conjugated with galactose ligand via a longer spacer. The adhesion dynamics and final adhesion energy of HepG2 cells depends both on the type of ligand-receptor interaction and the length of spacer between the ligand and substrate. Most importantly, new biophysical insights into the initial hepatocyte attachment that are critical for hepatocyte culture are provided through the decomposition of two-dimensional spreading and adhesion contact formation on bio-functional substrates.