Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

An Experimentally Derived Stress Resultant Shell Model for Heart Valve Dynamic Simulations

In order to achieve a more realistic and accurate computational simulation of native and bioprosthetic heart valve dynamics, a finite shell element model was developed. Experimentally derived and uncoupled in-plane and bending behaviors were implemented into a fully nonlinear stress resultant shell element. Validation studies compared the planar biaxial extension and three-point bending simulations to the experimental data and demonstrated excellent fidelity. Dynamic simulations of a pericardial bioprosthetic heart valve with the developed shell element model showed significant differences in the deformation characteristics compared to the simulation with an assumed isotropic bending model. The new finite shell element model developed in the present study can also incorporate various types of constitutive models and is expected to help us to understand the complex dynamics of native and bioprosthetic heart valve function in physiological and pathological conditions.     

Effect of a modified, well-tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio

One hundred one patients with coronary artery disease and pretreatment ratios of total cholesterol to high density lipoprotein (HDL) cholesterol greater than 4.0 were treated with niacin, commencing at low dosages (100 to 250 mg twice daily) and gradually increasing the dosage over 4 to 8 weeks to 1,000 mg twice daily. Dosage adjustments were made to minimize side effects. At a mean follow-up duration of 11 +/- 7 months, and a mean dosage of 1,415 +/- 698 mg/day, the group had a 13% reduction in total cholesterol, 31% increase in HDL and 32% decrease in the cholesterol to HDL ratio. A subgroup of 62 patients taking greater than 1,000 mg/day of niacin had an 18% reduction in total cholesterol, 32% increase in HDL and 36% improvement in the cholesterol to HDL ratio. A subgroup of 39 patients taking less than or equal to 1,000 mg/day of niacin had only a 5% reduction in total cholesterol, although a 29% increase in HDL and a 24% decrease in the cholesterol to HDL ratio were recorded. Side effects of niacin were reported in 38% of the patients, but led to discontinuation of therapy in only 4. Niacin can be administered in a fashion that is well tolerated, inexpensive and very effective in improving the cholesterol to HDL ratio.     

Studies on the effect of vanadate on endocytosis and shape changes in human red blood cells and ghosts

When amphipathic cationic drugs are added to intact human RBCs, the RBCs first undergo a stomatocytic shape change and then, if relatively large amounts of drug are added and if the metabolic state of the RBC is appropriate, endocytic vacuoles form. Vanadate has a structural similarity to the transition state of phosphate, which presumably accounts for its ability to inhibit phosphohydrolases, although other actions of vanadate have been described. Vanadate inhibited three forms of drug-induced endocytosis in intact RBCs despite the fact that the three drugs chosen (primaquine, chlorpromazine, and vinblastine) are known to have differing requirements for RBC ATP. Vanadate also inhibited the stomatocytic shape change produced by primaquine, chlorpromazine, and vinblastine, but not the stomatocytosis produced by low pH. Vanadate had no effect on RBC echinocytosis produced by lysophosphatidylcholine. In studying endocytosis in hypotonic, leaky, "white" ghosts, we discovered that vanadate inhibited only the endocytosis produced by Mg-ATP and not the endocytosis produced by manipulations that directly attack the cytoskeletal proteins. These findings suggest that ATP hydrolysis has a role in some forms of amphipathic cation-induced stomatocytosis and endocytosis in intact RBCs. In addition, studies in ghosts support the idea that Mg-ATP does indeed produce "energized" endocytosis dependent on utilization or hydrolysis of ATP.     

A New Standard for Advance Care Planning (ACP) Conversations in the Hospital: Results from a Delphi Panel

BackgroundFewer than half of the US population has an advance healthcare directive. Hospitalizations offer a key opportunity for clinicians to engage patients in advance care planning (ACP) conversations. Guidelines suggest screening for the presence of “serious illness” but do not further specify how to prioritize the 12.4 million patients hospitalized each year.ObjectiveTo establish a normative standard for prioritizing hospitalized patients for ACP conversations.Design and SettingA modified Delphi study, with three iterative rounds of online surveys.ParticipantsMulti-disciplinary group of US-based clinicians with research and practical expertise in ACP.Main MeasuresIndirect and direct elicitation of short-term and 1-year risk of mortality that prompt experts to prioritize ACP conversations for hospitalized adults.Main resultsFifty-seven of 108 (52%) candidate panelists completed round 1, and 47 completed rounds 2 and 3. Panelists were primarily physicians (84%), with significant experience (mean years 23 [SD 9.8]), who either taught (55%) and/or performed research about ACP (55%). In round 1, > 70% of panelists agreed that all hospitalized adults ≥ 65 years should have an ACP conversation before discharge, but disagreed about the timing and content of the conversation. By round 3, > 70% of participants agreed that patients with either high (> 10%) short-term or high (≥ 34%) 1-year risk of mortality should have a goals of care conversation (i.e., focused on preferences for near-term treatment), while patients with low (≤ 10%) short-term and low (< 19%) 1-year risk of mortality warranted an ACP conversation (i.e., focused on preferences for future care) before discharge.LimitationsUse of case vignettes to elicit clinician judgment; response rate.ConclusionsPanelists agreed that clinicians should have an ACP conversation with all hospitalized adults over 65 years in an ACP conversation, adjusting the content and timing of the conversation conditional on the patient’s risk of short-term and 1-year mortality.Electronic supplementary materialThe online version of this article (10.1007/s11606-020-06150-0) contains supplementary material, which is available to authorized users.KEY WORDS: advance care planning, Delphi survey, physician performance

Numerous stakeholders recommend advance care planning (ACP) to improve the quality of care that patients receive as they approach the end-of-life.^1–3 Hospitalizations offer one opportunity for clinicians to initiate ACP conversations with patients.⁴ However, high-quality conversations, which allow patients to reveal (or potentially construct) their preferences, require clinicians to have the communication skills, the willingness to engage in emotionally complex interactions, and the time necessary to facilitate this process.^5–8 Guidelines suggest screening patients to prioritize those with near-term mortality or morbidity risk based on the presence of “serious illness,” defined as the presence of a condition that carries a high risk of mortality or impacts quality of life.⁴ In the absence of a quantifiable definition of this term, the surprise question (which requires the treating clinician to consider whether or not he/she would be surprised if the patient died in the next year) has been widely promoted.^{9, 10} Pooled results of two different meta-analyses, however, suggest poor to modest accuracy of the surprise question for predicting death at 12 months.^{10, 11} Efforts to improve the quality of care for patients at the end-of-life therefore require better strategies to screen and prioritize patients for ACP conversations.The objective of this study was to establish a consensus-based normative standard for risk of mortality that should prompt hospitalists to have an ACP conversation with their patients. Recognizing that people, even experts, struggle with probability-based judgments, we embedded a behavioral experiment within a Delphi process, sequentially presenting experts with cases selected from across the distribution of mortality risk and observing their judgments as the sampling frame changed. We hypothesized that experts would be more likely to recommend an immediate ACP conversation as the risk of mortality increased.     

Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA

Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state.     

Mental disorders and drug abuse in persons living with HIV/AIDS

This article reviews the literature on the prevalence of mental and substance use disorders among persons living with HIV/AIDS. Drug use, both injection and non-injection, substantially increases the risk for HIV infection. While injection drug users have the highest prevalence rates for HIV, substantially elevated rates of HIV infection are also present among crack cocaine users and individuals with substance use disorders generally. Persons with HIV/AIDS and a mental and/or substance use disorder have highly variable patterns of accessing services. Persons with HIV/AIDS who have a serious mental illness are more highly involved with services than other groups. Most individuals with co-occurring disorders report some involvement with outpatient primary medical care, although ancillary services such as mental health and substance abuse treatment, transportation assistance, and case management improve involvement in medical care. Women with HIV/AIDS and co-occurring mental and substance use disorders experience unique vulnerabilities, particularly those related to exposure to traumatic events. Given the complexity of needs with which triply or multiply diagnosed individuals present, effective treatment programmes are likely to be those that provide some degree of integrated care.