A quantitative systems pharmacology model of hyporesponsiveness to erythropoietin in rats

Journal of Pharmacokinetics and Pharmacodynamics - Recombinant human erythropoietin (rHuEPO) is effective in managing chronic kidney disease and chemotherapy-induced anemia. However,...     

Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro

Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.     

Investigating the Use of Denosumab in the Treatment of Acute Charcot Neuroarthropathy

Charcot neuroarthropathy is a devastating condition, most commonly affecting poorly controlled diabetic patients with peripheral neuropathy. Pharmacological options for the condition are currently limited. The purpose of this study was to investigate the potential of Prolia® (denosumab) as a safe and feasible option in the treatment of acute Charcot neuroarthropathy. A total of 7 consecutive subjects were enrolled and followed for 1 year. Subjects received a single one-time injection of denosumab 60 mg. Subjects also received standard of care treatment, which included total contact casting, restricted weightbearing status, and biweekly office visits until normalization of the skin temperature gradient. Overall, the pharmaceutical treatment was generally well-tolerated. One subject developed a diabetic foot infection with cellulitis of the contralateral lower extremity, which occurred following the 6-month follow-up visit and which resolved with oral antibiotics One subject identified transient muscle pain in the same upper extremity which received the injection. Subjects were found to exit the acute phase of the condition at an average of 52.00 ± 17.89 days after their injection, which was defined by normalization of skin temperature to within 2°C of the contralateral foot. Treatment of acute Charcot neuroarthropathy with denosumab was well-tolerated in this open-label, pilot study. The clinical outcomes suggest that the medication may be efficacious, though a larger sample size would be needed to confirm these preliminary results. An adequately-powered, randomized, controlled study may be an appropriate follow-up.     

Plombage for Hemoptysis Control in Pulmonary Aspergilloma: Safety and Effectiveness of Forgettable Surgery in High-Risk Patients

Objectives: To evaluate plombage surgery for hemoptysis control in pulmonary aspergilloma in high-risk patients.Methods: This study was carried out on 75 pulmonary aspergilloma patients presenting with hemoptysis that underwent a plombage surgery for approximately 7 years (November 2011–September 2018) at Pham Ngoc Thach Hospital. They revisited the hospital 6 months after plombage surgery and considered plombage removal. The group whose plombage was removed was compared with that whose plombage was retained 6 and 24 months after surgery.Results: Hemoptysis reduced significantly after surgery. Hemoptysis ceased in 91.67% of the patients and diminished in 8.33% of the patients 6 months after surgery. Similarly, hemoptysis ceased in 87.32% of the patients and diminished in 12.68% of the patients 24 months after surgery. Body mass index (BMI) index, Karnofsky score, and forced expiratory volume in one second (FEV1) increased. Plombage surgery was performed with operative time of 129.5 ± 36.6 min, blood loss during operation of 250.7 ± 163.1 mL, and the number of table tennis balls of 4.22 ± 2.02. No deaths related to plombage surgery were recorded. Plombage was removed in 29 cases because of patients’ requirements (89.8%), infection (6.8%), and pain (3.4%). There were no patient developing complications after the treatment and there were no statistically significant differences between the two groups.Conclusions: Plombage surgery is safe and effective for hemoptysis control in pulmonary aspergilloma. To minimize the risk of long-term complications, surgeons should remove the plombage 6 months after the initial operation.     

Impact of the affordable care act’s medicaid expansion on burn outcomes and disposition

BackgroundWe aimed to analyze the impact of the Affordable Care Act’s Medicaid Expansion on clinical outcomes and patient disposition after burn injury. We hypothesized that increased insurance coverage results in improved outcomes and higher rates of discharge to inpatient rehabilitation.MethodsWe reviewed the University of Washington Regional Burn Center registry data for patients admitted from 2011 to 2018. Patients were grouped into two categories: before (2011–2013) and after (2015?2018) Medicaid expansion; we excluded 2014 data to serve as a washout period. Outcomes assessed included length of hospital stay, patient disposition, and mortality. Multivariable logistic and linear regression models with covariates for sex, age, burn size, ethnicity ethnicity, distance from burn center, etiology of burn, and presence of inhalation injury were used to determine the impact of Medicaid expansion on outcomes.ResultsRates of uninsured patients decreased while Medicaid coverage increased. Despite increased median burn size after Medicaid expansion, inpatient mortality rates did not change, but average acute care length of stay increased. More patients were discharged to rehabilitation centers.ConclusionsOur study corroborates prior findings of increased insurance coverage since Medicaid expansion. Increased insurance coverage is associated with higher rates of discharge to inpatient rehabilitation programs after burn injury.     

Uveitis, an under-recognized adverse effect of pamidronate. Case report and literature review

Ophthalmologic adverse effects of bisphosphonate therapy are infrequent and of unclear pathogenesis. The most common has been anterior uveitis, of which 18 cases have been reported. Onset was within 24 to 48 hours after infusion initiation, and both eyes were affected in most patients. The outcome was favorable within a few days after bisphosphonate discontinuation and topical glucocorticoid therapy, although rechallenge was frequently followed by a recurrence. Bisphosphonates are being used successfully in an increasingly broad range of disorders. We report a case of pamidronate-induced anterior uveitis and present a review of the relevant literature.     

Detection of growth-stimulating activity in the proximal small intestine during weaning in the suckling rat

Adaptive changes in enzyme expression and cell proliferation occur in the small intestine of the suckling rat at the beginning of the 3rd postnatal week. This physiological adaptation can be modulated by factors including diet or glucocorticoids. We have previously described an intestinal growth-stimulating fraction derived from the remnant small bowel after resection and found that enteral nutrition is critical for its detection. In view of the similarity between the changes in cell proliferation that occur between 15 and 22 days postnatally and those immediately after resection, we sought to determine whether the small intestinal mucosa of the neonatal rat also contains a similar growth-stimulating fraction. Our results show that extracts of the proximal intestine prepared from 15-day-old rats do contain the growth-stimulating fraction. The activity was not detectable in maternal milk nor in the intestinal extract from 8-day-old rats. When the suckling rats were deprived of solid food, the activity was not detectable in the 15-day-old group. Gel filtration of the acidic extract on a G-25 Sephadex column revealed that the active component is made up of two molecular weight species (approximately 4,500 and 1,500 daltons) similar to that described in the proximal intestine of the postresectional model. These findings suggest that dietary factors may play a role in modulating the proliferative changes that occur at the time of weaning by way of the growth-stimulating fraction.     

L'alimentation de compl��ment du jeune enfant apr��s la d��valuation du franc CFA: deux ��tudes de cas en milieu urbain, au Congo et au S��n��gal.

Developing countries frequently see their currency depreciated to varying degrees. The consequences of such monetary disturbances on the nutrition of young children are not well known, though children are the most vulnerable in nutritional terms. One year after the 50% devaluation of the CFA Franc (communauté financière africaine, "African Financial Community"), which took place on 12 January 1994 simultaneously in fourteen countries, nine of which are on the UNDP list of least developed countries, we wanted to find out the long-term effects of the devaluation, and the strategies that families had adopted to cope with it. In Brazzaville, Congo, in December 1994, an epidemiological survey was conducted on a representative sample of 893 children between the ages of 4 and 12 months in two districts, and indicators of child nutrition were established. A comparable survey had been conducted in December 1993, before the devaluation. In Senegal, in the absence of a previous survey which could be used in comparison, a qualitative survey using RAP methodology, was conducted in January 1995 in two towns near the capital. In three districts in each of these towns, a cluster of ten plots was chosen at random and surveyed, with a combination of semi-structured individual interviews with mothers (n = 60) and group interviews with all the women together (n = 6). The information was put together with interviews of 25 local traders selling food. In the Congo, comparison of the two surveys shows that the practice of breast-feeding had hardly changed, nor had the age at which baby food was introduced (90% of children of 4-5 months take semi-solid and solid foods); on the other hand, more children are being given the ordinary family meal earlier, at 6-9 months. The proportion of baby foods based on commercially imported flour has fallen (from 32% in 1993 to 18% in 1994), and has been replaced with local products based on maize; this change is more marked among poorer families. The low nutritional value of such preparations is in part compensated by the addition of sugar, though less milk is added (28% in 1994 as opposed to 43% in 1993). In Senegal, mothers do not seem to have changed their breast-feeding practices either, the age at which baby foods are introduced, or the number of times they are provided daily. The most important change is the drop in quality of food given to children, and the poorer family food for the older children. The partial switch from imported products to local produce was an expected consequence of devaluation; it is clearly confirmed here for nutrition of young children, with the consequent loss of nutritional quality (a reduction in energy density and in nutrients). The first thing needed is, therefore, an improvement in local manufacture of food supplements of good nutritional quality, for young children. Mothers also complain of the increased difficulty in managing a family diet so as to take account of economic needs, cultural values and nutrition. They therefore criticize a number of nutritional education messages that are clearly no longer appropriate to the new economic context. Finally the fact that young children are getting poorer quality nutrition is worrying for the future: if it lasts, the nutritional status of children will deteriorate; whenever possible, monitoring must be established so that measures can be taken when necessary to forestall any dramatic deterioration that would endanger the health of the children.