Evolution of Investigating Informed Assent Discussions about CPR in Seriously Ill Patients.

CONTEXT: Outcomes after cardiopulmonary resuscitation (CPR) remain poor. We have spent 10 years investigating an "informed assent" (IA) approach to discussing CPR with chronically ill patients/families. IA is a discussion framework whereby patients extremely unlikely to benefit from CPR are informed that unless they disagree, CPR will not be performed because it will not help achieve their goals, thus removing the burden of decision-making from the patient/family, while they retain an opportunity to disagree. OBJECTIVES: Determine the acceptability and efficacy of IA discussions about CPR with older chronically ill patients/families. METHODS: This multi-site research occurred in three stages. Stage I determined acceptability of the intervention through focus groups of patients with advanced COPD or malignancy, family members, and physicians. Stage II was an ambulatory pilot randomized controlled trial (RCT) of the IA discussion. Stage III is an ongoing phase 2 RCT of IA versus attention control in in patients with advanced chronic illness. RESULTS: Our qualitative work found the IA approach was acceptable to most patients, families, and physicians. The pilot RCT demonstrated feasibility and showed an increase in participants in the intervention group changing from "full code" to "do not resuscitate" within two weeks after the intervention. However, Stages I and II found that IA is best suited to inpatients. Our phase 2 RCT in older hospitalized seriously ill patients is ongoing; results are pending. CONCLUSIONS: IA is a feasible and reasonable approach to CPR discussions in selected patient populations.

Preliminary observations on whole-ovary xenotransplantation as an experimental model for fertility preservation.

Ovarian tissue preservation and retransplantation is a promising strategy to restore fertility in cancer survivors. Ischaemia accompanying ovarian tissue grafting, however, can lead to significant follicle loss. Transplantation of the whole ovary by vascular anastomosis has been considered as an alternative to prevent widespread ischaemic damage. In this study, the feasibility and function of transplanting whole ovary with intact vasculature were evaluated, with the goal of developing a xenograft model for studies using donated human ovaries. Whole-swine ovaries with vascular pedicles were perfused and transplanted as intact ovaries by anastomosis into irradiated ovariectomized nude rats (n = 10). The observation period was between 1 and 4 weeks. Fresh swine ovaries served as controls (n = 10). Ovarian stroma and follicle populations were assessed through histological examination in both transplanted and control ovaries. Most of the transplanted whole ovaries (n = 6) maintained stromal quality and all preantral follicle classes were represented, although follicle numbers decreased compared with fresh control. Four transplanted ovaries were fibrotic after 1-4 weeks within the nude rat. Our results demonstrate transplantation of whole-pig ovary into nude rats is possible and support development of this xenograft model system for human studies.

Spontaneous antral follicle formation and metaphase II oocyte from a non-stimulated prepubertal ovarian tissue xenotransplant.

BACKGROUND: Current strategies in cancer treatment have markedly increased the rates of remission and survival for cancer patients, but are often associated with subsequent sterility. While there are various options available to an adult female depending on the patient's particular situation, the only realistic option for preserving fertility in prepubertal females is to cryopreserve ovarian tissue. This is the first report of a morphologically mature oocyte collected from non-stimulated prepubertal ovarian tissue xenotransplants. METHODS: Ovarian tissue from a 6 year old patient suffering from nephroblastoma was removed and cryopreserved for fertility preservation. The frozen-thawed ovarian tissue fragments were xenotransplanted to bilaterally oophorectomized severe combined immunodeficiency (SCID) mice to assess follicle development. RESULTS: Antral follicle formation occurred post-xenotransplantation in a single ovarian fragment without exogenous hormone stimulation. A morphologically maturing oocyte was harvested from these follicles. CONCLUSIONS: Prepubertal human ovarian follicles and oocytes can be matured after xenotransplantation even without exogenous hormone stimulation. These results indicate that tissue collected from prepubertal patients can support fertility in cancer survivors.

Diagnostic imaging and risk stratification of patients with acute pulmonary embolism.

Pulmonary embolism (PE) is the third most common acute cardiovascular disease after myocardial infarction and stroke. The prompt diagnosis, risk stratification, and treatment of patients with acute PE can reduce mortality. Multidetector row computed tomography pulmonary angiography (CTPA) is the most common study used to make the diagnosis of acute PE. CTPA may additionally identify right heart dysfunction or alternative diagnoses. There is a growing body of evidence that computed tomography signs of right heart failure predict patients at higher risk of mortality. At the same time, CTPA has about a 6-fold greater whole body effective dose than ventilation-perfusion (V/Q) scintigraphy, and a much higher dose to breast tissue in particular. V/Q scintigraphy should be considered for patients with contraindications to iodinated contrast or for patients with normal chest radiographs, especially young women. Compression ultrasonography of the proximal lower extremities, an imaging study without ionizing radiation, should be considered for patients suspected of acute PE with signs of lower extremity deep venous thrombosis or for patients with negative CTPA or V/Q scan with discordant clinical probability. This article reviews factors affecting the selection of the best imaging test for a particular patient suspected of acute PE, performance characteristics of diagnostic imaging tests, and imaging findings that correlate with higher mortality.

Elevated international normalized ratio values associated with concomitant use of warfarin and ceftriaxone.

PURPOSE: The case of a patient receiving long-term warfarin therapy who experienced elevated International Normalized Ratio (INR) values on two occasions after injections of ceftriaxone is reported. SUMMARY: An elderly woman (age, 67 years) with multiple comorbidities who had been receiving warfarin therapy for about 8 years was given an intramuscular injection of ceftriaxone 1 g for the treatment of a urinary tract infection. Four days later, her INR (which had recently ranged from 1.9 to 3.0 at a weekly warfarin dosage of 52.5-54.5 mg) was 10.74. One scheduled warfarin dose was withheld and 5 mg of phytonadione administered; one day later, the INR was 3.4 (goal, 2.5-3.5). INR values remained stable for several weeks until the patient again received a 1-g ceftriaxone injection for an infection (she was also prescribed oral cefuroxime and phenazopyridine); four days later, the INR was 16.99. Again, the scheduled warfarin dose was withheld and 5 mg of phytonadione administered. One day later, the INR had declined to 4.6 but remained above the target range; therefore, warfarin was withheld for a second day, after which the patient received 7.5 mg of warfarin sodium daily for two days, resulting in an INR decrease to 2.1. The patient continued to receive 7.5 mg of warfarin sodium daily, and at one-week follow-up the INR value (2.5) was within the therapeutic range. CONCLUSION: A 67-year-old American Indian woman with previously stable INR values during long-term warfarin therapy after mitral valve replacement surgery had INR elevations on two occasions after receiving ceftriaxone for urinary tract infections.

Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function.

BACKGROUND: Asthma is a chronic inflammatory disease of the airway that is characterized by a Th2-type of immune response with increasing evidence for involvement of Th17 cells. The role of IL-6 in promoting effector T cell subsets suggest that IL-6 may play a functional role in asthma. Classically IL-6 has been viewed as an inflammatory marker, along with TNFalpha and IL-1beta, rather than as regulatory cytokine. OBJECTIVE: To investigate the potential relationship between IL-6 and other proinflammatory cytokines, Th2/Th17 cytokines and lung function in allergic asthma, and thus evaluate the potential role of IL-6 in this disease. METHODS: Cytokine levels in induced sputum and lung function were measured in 16 healthy control and 18 mild-moderate allergic asthmatic subjects. RESULTS: The levels of the proinflammatory biomarkers TNFalpha and IL-1beta were not different between the control and asthmatic group. In contrast, IL-6 levels were specifically elevated in asthmatic subjects compared with healthy controls (p < 0.01). Hierarchical regression analysis in the total study cohort indicates that the relationship between asthma and lung function could be mediated by IL-6. Among Th2 cytokines only IL-13 (p < 0.05) was also elevated in the asthmatic group, and positively correlated with IL-6 levels (rS = 0.53, p < 0.05). CONCLUSIONS: In mild-moderate asthma, IL-6 dissociates from other proinflammatory biomarkers, but correlates with IL-13 levels. Furthermore, IL-6 may contribute to impaired lung function in allergic asthma.

Effect of dietary constituents with chemopreventive potential on adduct formation of a low dose of the heterocyclic amines PhIP and IQ and phase II hepatic enzymes.

We conducted a study to evaluate dietary chemopreventive strategies to reduce genotoxic effects of the carcinogens 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). PhIP and IQ are heterocyclic amines (HCAs) that are found in cooked meat and may be risk factors for cancer. Typical chemoprevention studies have used carcinogen doses many thousand-fold higher than usual human daily intake. Therefore, we administered a low dose of [14C]PhIP and [3H]IQ and utilized accelerator mass spectrometry to quantify PhIP adducts in the liver, colon, prostate, and blood plasma and IQ adducts in the liver and blood plasma with high sensitivity. Diets supplemented with phenethylisothiocyanate (PEITC), genistein, chlorophyllin, or lycopene were evaluated for their ability to decrease adduct formation of [14C]PhIP and [3H]IQ in rats. We also examined the effect of treatments on the activity of the phase II detoxification enzymes glutathione S-transferase (GST), UDP-glucuronyltransferase (UGT), phenol sulfotransferase (SULT) and quinone reductase (QR). PEITC and chlorophyllin significantly decreased PhIP-DNA adduct levels in all tissues examined, which was reflected by similar changes in PhIP binding to albumin in the blood. In contrast, genistein and lycopene tended to increase PhIP adduct levels. The treatments did not significantly alter the level of IQ-DNA or -protein adducts in the liver. With the exception of lycopene, the treatments had some effect on the activity of one or more hepatic phase II detoxification enzymes. We conclude that PEITC and chlorophyllin are protective of PhIP-induced genotoxicity after a low exposure dose of carcinogen, possibly through modification of HCA metabolism.