A Multidisciplinary Approach for the Management of Portal Vein Thrombosis.

Portal venous thrombosis (PVT) is an uncommon disease associated with highly morbid conditions such as intestinal ischemia and portal hypertension. Patients at higher risk of developing PVT include those with cirrhosis, malignancy, or prothrombotic states. The mainstay of treatment is early initiation of anticoagulation. The first case is a 49-year-old female diagnosed with a cecal mass and PVT. She was started on anticoagulation and underwent a right hemicolectomy with several small bowel resections. She developed portal hypertension that required TIPS and mechanical thrombectomy. The second patient is a 65-year-old female found to have PVT. She was anticoagulated with heparin and given systemic TPA. She developed intestinal ischemia and portal hypertension requiring small bowel resection, TIPS, and mechanical thrombectomy. These cases give insight into the impact of a multidisciplinary team approach to PVT. The role and timing of endovascular treatment is not well established and needs to be further investigated.

Could Home Human Immunodeficiency Virus Self-Testing Ever Become a Game Changer?

Could home human immunodeficiency virus (HIV) self-testing make a major difference in identifying persons with undiagnosed HIV in the United States? We argue that approval of new self-test assays for home use would help but must be combined with extensive investment in community outreach and linkage to care to make an impact.

Evolution of water conservation in humans.

To sustain life, humans and other terrestrial animals must maintain a tight balance of water gain and water loss each day.1-3 However, the evolution of human water balance physiology is poorly understood due to the absence of comparative measures from other hominoids. While humans drink daily to maintain water balance, rainforest-living great apes typically obtain adequate water from their food and can go days or weeks without drinking4-6. Here, we compare isotope-depletion measures of water turnover (L/d) in zoo- and rainforest-sanctuary-housed apes (chimpanzees, bonobos, gorillas, and orangutans) with 5 diverse human populations, including a hunter-gatherer community in a semi-arid savannah. Across the entire sample, water turnover was strongly related to total energy expenditure (TEE, kcal/d), physical activity, climate (ambient temperature and humidity), and fat free mass. In analyses controlling for those factors, water turnover was 30% to 50% lower in humans than in other apes despite humans' greater sweating capacity. Water turnover in zoo and sanctuary apes was similar to estimated turnover in wild populations, as was the ratio of water intake to dietary energy intake (∼2.8 mL/kcal). However, zoo and sanctuary apes ingested a greater ratio of water to dry matter of food, which might contribute to digestive problems in captivity. Compared to apes, humans appear to target a lower ratio of water/energy intake (∼1.5 mL/kcal). Water stress due to changes in climate, diet, and behavior apparently led to previously unknown water conservation adaptations in hominin physiology.

Human Immunodeficiency Virus Training Pathways in Residency: A National Survey of Curricula and Outcomes.

BACKGROUND: The Ending the HIV Epidemic initiative, which aims to decrease the annual incidence of HIV infections in the United States (US) by 90% over the next decade, will require growth of a limited HIV provider workforce. Existing HIV training pathways within Family Medicine (FM) and Internal Medicine (IM) residency programs may address the shortage of HIV medical providers, but their curricula and outcomes have not previously been assessed. METHODS: We identified HIV residency pathways via literature review, Internet search, and snowball sampling and designed a cross-sectional study of existing HIV pathways in the US. This survey of pathway directors included 33 quantitative items regarding pathway organization, curricular content, graduate outcomes, and challenges. We used descriptive statistics to summarize responses. RESULTS: Twenty-five residency programs with dedicated HIV pathways in the US were identified (14 FM and 11 IM), with most located in the West and Northeast. All 25 (100%) pathway directors completed the survey. Since 2006, a total of 228 residents (77 FM and 151 IM) have graduated from these HIV pathways. Ninety (39%) of 228 pathway graduates provide primary care to persons with HIV (PWH). CONCLUSIONS: HIV pathways are effective in graduating providers who can care for PWH, but generally are not located in nor do graduates practice in the geographic areas of highest need. Our findings can inform quality improvement for existing programs, development of new pathways, and workforce development strategies. Specifically, expanding pathways in regions of greatest need and incentivizing pathway graduates to work in these regions could augment the HIV workforce.

Brief Report: Weight Gain Following ART Initiation in ART-Naïve People Living With HIV in the Current Treatment Era.

OBJECTIVES: Evaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era. METHODS: Between 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time. RESULTS: Mean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens. CONCLUSIONS: There is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

Evidence-Based Valuation in Oncology:: Lessons Learned from a Case Study.

BACKGROUND: Value demonstration in health care remains a challenge. This paper examines traditional approaches to pricing and the evolution of value-based pricing (VBP), and proposes a new framework for evidence-based valuation (EBV). The main objective of EBV is to estimate the value-based pricing range for the new medicine, identify key product attributes that drive value as perceived by various stakeholders, and then elucidate the requisite evidence to support those value claims. METHODS: EBV centers on a structured framework for estimating a drug's price based on its perceived value to various stakeholders. The EBV framework consists of identifying key value attributes that drive adoption of a drug in a given therapeutic area; gaining insights into stakeholder value considerations and evidence requirements; and quantifying stakeholders' perceptions of specific value attributes within pricing premiums. RESULTS: An example demonstrates the application of the EBV framework in a simplified manner for 3 drugs indicated for renal cell carcinoma, 3 drugs for prostate cancer, and 1 drug for melanoma. HTAs, published trial results, and publications archived in PubMed between 2005 and 2013 were analyzed to identify key value attributes. The following 5 attributes were considered: overall survival (OS), progression-free survival (PFS), population size, trial comparator, and adverse events. CONCLUSIONS: The method described offers a means to appraise pharmaceuticals in an environment increasingly focused on evidence-based medicine and value-based health care.

Using an Innovative Telehealth Model to Support Community Providers Who Deliver Perinatal HIV Care.

Mountain West AETC (AIDS Education and Training Center) ECHO (Extension for Community Healthcare Outcomes), a longitudinal HIV telemen-toring program, connects community providers and a multidisciplinary specialist team at the University of Washington. The program employs focused lectures and real-time case discussions to educate and support providers in low-resource and rural settings. We assessed the impact of the program on management of perinatal HIV through surveying community providers who participate, and reviewing cases presented by providers for consultation. One hundred percent of providers who presented a perinatal HIV case for ECHO consultation reported that presentation "very much" impacted management of the case, and 93% of survey respondents reported that ECHO participation helped them stay up to date on national perinatal HIV guidelines. All 13 cases had the successful outcome of prevention of mother-to-child transmission of HIV. The ECHO model can effectively support and educate community providers who care for HIV-infected pregnant women.

Palliative care in people with idiopathic Parkinson's disease who die in hospital.

BACKGROUND: The UK National Institute for Health and Clinical Excellence guidelines state that palliative care options for people with Parkinson's disease (PD) should be discussed. AIMS: To investigate whether palliative care guidelines are adhered to for people with PD who die in hospital. SETTING/PARTICIPANTS: The medical notes of all people with a diagnosis of idiopathic PD who were living in two adjacent areas of northeast England and who died over a 3-year period were examined. Demographic data and specific information regarding events around the time of death were recorded. RESULTS: For the 236 patients identified, the average age at death was 82.8 years. Of these patients, 110 (46.6%) died in hospital, 56 (23.7%) at home, 59 (25.0%) in a care home and for 11 patients (4.7%) the place of death was not recorded. For those who died in hospital, only three patients, and seven relatives of patients, had had a recorded discussion with a clinician regarding their preferred place of death and only 15 (13.6%) were referred to a specialist palliative care team. Forty-six patients (41.8%) were placed on the Liverpool Care Pathway. CONCLUSIONS: For those dying in hospital, there are few previously documented end-of-life care discussions with patients or their relatives. The use of end-of-life pathways and access to specialist palliative care is variable. Following the Neuberger report, the Liverpool Care Pathway is to be replaced with individual end-of-life care plans. It is important to engage patients, and their relatives, in decision making regarding preferences at the end of life.

Radiographic progression by Prostate Cancer Working Group (PCWG)-2 criteria as an intermediate endpoint for drug development in metastatic castration-resistant prostate cancer.

OBJECTIVE: To investigate the association of radiographic progression defined by Prostate Cancer Working Group (PCWG)-2 guidelines and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Two trials that used PCWG-2 guidelines to define progression were analysed: a randomized phase II trial (n = 221) comparing first-line docetaxel-prednisone plus AT-101 or placebo, and a phase III trial (n = 873) comparing prednisone plus sunitinib or placebo after docetaxel-based chemotherapy. Cox proportional hazards regression models were used to estimate the association of radiographic progression with OS. Landmark analyses compared progressing patients with those who had not progressed. Sub-analyses compared patients removed from trial for progression vs other reasons. RESULTS: An increased risk of death was seen for radiographic progression at landmark times from 6 to 12 months with docetaxel-based therapy (hazard ratio [HR] >1.7 at all time-points). An increased risk of death was also seen with post-docetaxel prednisone alone or with sunitinib for progression at landmark times from 2 to 8 months (HR >2.7 at all time-points). Kendall's τ was 0.50 (P < 0.001) in the setting of docetaxel-based therapy and 0.34 (P < 0.001) in the post-docetaxel setting for association between radiographic progression and death amongst patients with both events. Removal from study due to radiographic progression was associated with a significantly lower OS compared with removal for other reasons in both trials. Limitations of a retrospective analysis apply and there was no central radiology review. CONCLUSIONS: Radiographic progression by PCWG-2 criteria was significantly associated with OS in patients with mCRPC receiving first-line docetaxel-based chemotherapy or post-docetaxel therapy. With external validation as a surrogate endpoint in trials showing survival benefits, the use of radiographic progression-free survival may expedite drug development in mCRPC, which has been hampered by the lack of intermediate endpoints.

Efficacy of docetaxel-based chemotherapy following ketoconazole in metastatic castration-resistant prostate cancer: implications for prior therapy in clinical trials.

OBJECTIVES: Abiraterone acetate (AA) is a CYP17 inhibitor of androgen synthesis approved for use following docetaxel for metastatic castration-resistant prostate cancer (mCRPC); evaluation in the pre-docetaxel setting is ongoing. Given that the reported efficacy of AA is lower following docetaxel vs. pre-docetaxel, the potential exists for cross resistance given docetaxel's partly androgen receptor targeting activity. The efficacy of docetaxel following ketoconazole (KC), a weaker and nonspecific inhibitor of CYP17, may provide some insights into this potential interaction. We retrospectively evaluated the efficacy of every 3-week docetaxel with prednisone (DP) in mCRPC previously exposed to KC compared to KC-naive patients. MATERIALS AND METHODS: A randomized phase II trial of men with mCRPC treated with DP + AT-101 (bcl-2 inhibitor) vs. DP plus placebo was analyzed. Both arms were combined for analysis as no significant differences were seen. Overall survival (OS), progression-free survival (PFS), objective response (ORR), pain, and prostate-specific antigen (PSA) response rates were estimated with and without prior KC. Cox proportional hazards regression models were used to estimate the effect of covariates on OS. RESULTS: Of 220 evaluable men, 40 (18.2%) received prior KC. The median OS with DP-based therapy of KC-naive patients (18.3 months, 95% CI: 15.0, 24.5) and post-KC patients (17.0 months, 95% CI: 9.9, 20.4) was not statistically different (P = 0.20). After controlling for prognostic classifications, analyses demonstrated consistent trends for worsening of OS after KC, with (hazard ratios (HRs) 1.33-1.46. Similar unfavorable trends were observed for ORR, PSA declines, and PFS. CONCLUSIONS: In this hypothesis-generating analysis, patients treated with docetaxel-based chemotherapy following prior KC had numerically and consistently worse outcomes than patients not exposed to prior KC. Although the estimated differences did not attain statistical significance, evaluation of outcomes with docetaxel in particular, and all classes of novel and emerging agents following AA, is of clinical importance, given its more potent androgen synthesis inhibition compared with KC. Drug development should take into account the potential impact of previous therapy.

Neutropenia as a potential pharmacodynamic marker for docetaxel-based chemotherapy in men with metastatic castration-resistant prostate cancer.

BACKGROUND: Docetaxel clearance appears increased in men who are castrated. Neutropenia in cycle 1 may be a pharmacodynamic marker for docetaxel, which may enable tailored dosing in metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: The association of cycle 1 neutropenia with overall survival (OS) was examined post hoc in a randomized phase II trial of 221 men with mCRPC who received docetaxel-prednisone combined with placebo or AT-101 (bcl-2 inhibitor); weekly blood cell counts were performed during the first cycle. Patients from both arms were combined because no outcome and toxicity differences were observed. OS was calculated from randomization by the Kaplan-Meier method, and Cox proportional hazards regression models were used to estimate the association with OS. RESULTS: The difference in OS between men with day 8 ≥grade 3 neutropenia and those with ≤grade 2 neutropenia was significant after adjusting for trial stratification factors, pain, and performance status (hazard ratio [HR] 0.64; 2P = .048). Results were similar for logarithmic neutrophil counts adjusted for the risk group based on anemia, visceral metastasis, progression by bone scan and pain (HR 1.18; 2P = .07) for stratification factors (HR 1.20; 2P = .052) or both (HR, 1.20; 2P = .046). Men with ≥grade 3 neutropenia and ≥30% prostate-specific antigen level decline by day 90 had improved OS compared with men exhibiting neither (HR 0.51; 2P = .014). CONCLUSIONS: For patients with mCRPC who received docetaxel, ≥grade 3 neutropenia on day 8 was prognostic for improved OS, which suggests its utility as a pharmacodynamic marker, in this hypothesis-generating analysis. Exploration of dose escalation of docetaxel to attain ≥grade 3 neutropenia on day 8 may be warranted.

HIV-2 encephalitis: case report and literature review.

We report the case of a 59-year-old man who moved from Cape Verde to Massachusetts at the age of 29. He had multiple sexual contacts with female partners in Cape Verde and with West African women in Massachusetts, as well as multiple past indeterminate HIV-1 antibody tests. He presented to our facility with 2-3 months of inappropriate behaviors, memory impairment, weight loss, and night sweats, at which time he was found to have an abnormal enhancing lesion of the corpus collosum on brain magnetic resonance imaging (MRI). Laboratory testing revealed a CD4 count of 63 cells/mm(3), positive HIV-2 Western blot, serum HIV-2 RNA polymerase chain reaction (PCR) of 1160 copies per milliliter and cerebrospinal fluid (CSF) HIV-2 RNA PCR of 2730 copies per milliliter. Brain biopsy demonstrated syncytial giant cells centered around small blood vessels and accompanied by microglia, which correlated with prior pathologic descriptions of HIV-2 encephalitis and with well-described findings of HIV-1 encephalitis. Based on genotype resistance assay results, treatment guidelines, and prior studies validating success with lopinavir-ritonavir, he was treated with tenofovir-emtricitabine and lopinavir-ritonavir, which has led to virologic suppression along with steady neurologic and radiologic improvement, although he continues to have deficits.

Ability of C-reactive protein to complement multiple prognostic classifiers in men with metastatic castration resistant prostate cancer receiving docetaxel-based chemotherapy.

UNLABELLED: What's known on the subject? and What does the study add? Serum C-reactive protein (C-reactive protein) is emerging as a potential novel prognostic factor in metastatic castration-resistant prostate cancer (mCRPC). In the present study, a prospective trial was investigated retrospectively and a significant prognostic impact for C-reactive protein that was independent of multiple published prognostic models was identified in men receiving docetaxel-based chemotherapy for mCRPC. Prospective validation is warranted. OBJECTIVE: • Given the recent emergence of C-reactive protein levels as a novel prognostic factor in men with metastatic castration-resistant prostate cancer (mCRPC), we sought to evaluate the independent prognostic ability of C-reactive protein in the context of published prognostic nomograms, risk grouping and disease state models in men receiving docetaxel-based chemotherapy for mCRPC. PATIENTS AND METHODS: • A large randomized phase II trial (CS-205) of mCRPC patients who received docetaxel-prednisone + AT-101 (Bcl-2 inhibitor) or docetaxel-prednisone + placebo was analyzed retrospectively (n= 220). • Overall survival (OS), progression-free survival (PFS) and measures of discriminatory ability were assessed in a hypothesis-generating analysis using Cox regression and concordance probabilities. • Patients from both treatment groups were combined for this analysis because no significant differences in outcomes were observed. • Because some factors used in nomograms were not collected or defined differently, risk was estimated based on slightly modified versions of nomograms. RESULTS: • C-reactive protein was independently prognostic for OS and PFS (P ≤ 0.002) after adjusting for all modeled risk estimates and classifiers. • C-reactive protein showed a concordance probability of 0.65 for both OS and PFS. • A 10-factor modified prognostic model based on the TAX327 trial had the greatest observed discrimination ability for OS and PFS (concordance probability = 0.623 and 0.603, respectively) among the modified nomograms or classifiers. • Adding the TAX327 model risk estimates to C-reactive protein did not substantially increase discrimination ability over C-reactive protein alone. CONCLUSIONS: • Current prognostic classifications provide modest discrimination of outcomes in mCRPC receiving docetaxel-based chemotherapy, highlighting the need for improved risk-based models. • Baseline C-reactive protein appears to be an useful, independent prognostic factor and prospective external validation is warranted.

Evaluating the value of number of cycles of docetaxel and prednisone in men with metastatic castration-resistant prostate cancer.

BACKGROUND: The optimal number of 3-wk docetaxel plus prednisone (DP) cycles for metastatic castration-resistant prostate cancer (mCRPC) is unclear. OBJECTIVE: A retrospective analysis of two clinical trials was performed to evaluate the association of the number of cycles with overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: An exploratory analysis compared outcomes of 332 men who received DP in the TAX-327 trial, which stipulated up to 10 cycles, and 220 men who received DP in CS-205, a randomized phase 2 trial comparing DP plus AT-101 (bcl-2 inhibitor) versus DP plus placebo, which allowed up to 17 cycles. MEASUREMENTS: Patients who completed 10 cycles of DP without progression in both trials were included. Men in both arms of CS-205 were combined for analysis, as no significant differences in outcomes were observed. OS was estimated from the date of cycle 10 docetaxel infusion. RESULTS AND LIMITATIONS: The number of men receiving 10 cycles was similar (p=0.26) in the two trials (166 [50.0%] in TAX-327 vs 99 [45.0%] in CS-205; the latter group received a median of five additional cycles). Six- and 12-mo estimated survival after cycle 10 was 92.2% (95% confidence interval [CI], 86.9-95.4%) and 74.6% (CI, 67.2-80.5%) in TAX-327, compared with 92.8% (CI, 85.5-96.5) and 63.4% (CI, 51.8-72.9%) in CS-205. Subanalyses suggested that <10 cycles may have a negative impact and prostate-specific antigen (PSA) declines at cycle 10 may carry a favorable impact. The significance of continued PSA declines up to 17 cycles is unclear. Limitations of a retrospective analysis apply. CONCLUSIONS: A survival benefit was not detected with >10 cycles of DP in men with mCRPC in this retrospective hypothesis-generating analysis.

Double-blind, placebo-controlled, randomized phase 2 study of the proapoptotic agent AT-101 plus docetaxel, in second-line non-small cell lung cancer.

BACKGROUND: AT-101 is an inhibitor of Bcl-2 family proteins including Bcl-2, Bcl-xL, Mcl-1, and Bcl-w. In vivo and in vitro studies have exhibited broad activity of AT-101, including synergy with docetaxel in non-small cell lung cancer tumor models. METHODS: We conducted a prospective, randomized (1:1), double-blind, placebo-controlled phase 2 study. Eligible patients must have received one prior chemotherapeutic regimen for advanced or metastatic non-small cell lung cancer and may also have received therapy with an epidermal growth factor receptor inhibitor. Patients received AT-101 (40 mg b.i.d. × 3 days) or placebo in combination with docetaxel (75 mg/m on day 1) every 21 days. The primary endpoint was progression-free survival (PFS) as determined by independent review; other endpoints include overall survival and PFS by investigator determination. Approximately 102 patients were planned to provide 70 events (80% power, hazard ratio [HR] of 0.6, one-sided alpha of 0.1). RESULTS: : One hundred six patients were assigned to treatment and 105 patients received at least one dose of AT-101 or placebo. Baseline factors were balanced between treatment groups: median age 59 years; 77% men, and 79% current or former smokers. Ninety-three percent of patients had distant metastatic disease at randomization and 56% squamous histology. The most frequently reported adverse events were fatigue (18%), anemia (18%), and dyspnea (18%). No statistically significant differences in serious adverse events were observed between AT-101 and placebo; grade 1/2 headaches appeared more frequently with AT-101 (9% versus 0%) and neutropenia was reported more frequently in the docetaxel plus placebo arm compared with docetaxel plus AT-101 (17% versus 8%). Unlike trials with continuous daily dosing of AT-101, no cases of small bowel obstruction were reported. The response rate and median PFS were not different between the arms by independent review, PFS 7.5 weeks for docetaxel plus AT-101 and 7.1 weeks for docetaxel plus placebo arms (HR, 1.04; p = 0.57). The median overall survival was 7.8 months for docetaxel plus AT-101 versus 5.9 months for docetaxel plus placebo (HR, 0.82; p = 0.21). CONCLUSIONS: The primary endpoint of improved PFS for AT-101 plus docetaxel was not met. AT-101 plus docetaxel was well tolerated with an adverse event profile indistinguishable from the base docetaxel regimen. AT-101 is the first oral, pan Bcl-2 family inhibitor to exhibit a possible survival benefit in a randomized study.

Oxidative remobilization of biogenic uranium(IV) precipitates: effects of iron(II) and pH.

The oxidative remobilization of uranium from biogenic U(IV) precipitates was investigated in bioreduced sediment suspensions in contact with atmospheric O2 with an emphasis on the influence of Fe(II) and pH on the rate and extent of U release from the solid to the aqueous phase. The sediment was collected from the U.S. Department of Energy Field Research Center (FRC) site at Oak Ridge, Tennessee. Biogenic U(IV) precipitates and bioreduced sediment were generated through anaerobic incubation with a dissimilatory metal reducing bacterium Shewanella putrefaciens strain CN32. The oxidative remobilization of freshly prepared and 1-yr aged biogenic U(IV) was conducted in 0.1 mol/L NaNO3 electrolyte with variable pH and Fe(II) concentrations. Biogenic U(IV)O2(s) was released into the aqueous phase with the highest rate and extent at pH 4 and 9, while the U remobilization was the lowest at circumneutral pH. Increasing Fe(II) significantly decreased U remobilization to the aqueous phase. From 70 to 100% of the U in the sediments used in all the tests was extractable at the experiment termination (41 d) with a bicarbonate solution (0.2 mol/L), indicating that biogenic U(IV) was oxidized regardless of Fe(II) concentration and pH. Sorption experiments and modeling calculations indicated that the inhibitive effect of Fe(II) on U(IV) oxidative remobilization was consistent with the Fe(III) oxide precipitation and U(VI) sorption to this secondary phase.

Specific compliance and gas exchange during high-frequency oscillatory ventilation.

OBJECTIVES: To evaluate the use of specific compliance (static compliance/functional residual capacity) to adjust mean airway pressure, resulting in optimal gas exchange during high-frequency oscillatory ventilation in a surfactant-deficient newborn piglet. DESIGN: Prospective controlled animal study. SETTING: Laboratory. SUBJECTS: Eight newborn piglets at 5 days of age. BACKGROUND: High-frequency oscillatory ventilation enables the use of relatively high mean airway pressures without the lung damage associated with conventional positive pressure ventilation. Mean airway pressures can be increased, resulting in static lung expansion that approaches total lung capacity with its negative impact on venous return. Therefore, knowledge of lung volume is important for safe patient management. A simple, noninvasive technique to enable the clinician to determine the optimal mean airway pressure likely would improve patient management. INTERVENTIONS: The lungs were lavaged after placement of central catheters and tracheostomy to lower respiratory system compliance and worsen ventilation perfusion matching. The animals were ventilated with high-frequency oscillatory ventilation at the same mean airway pressure as before lung lavage. Mean airway pressures then were increased in a step-wise fashion up to 30 cm H2O or until clinical deterioration occurred. All other ventilator variables, Fio2, frequency, and pressure amplitude were constant throughout the experiment. MEASUREMENTS AND MAIN RESULTS: Before lavage and at each level of mean airway pressure after lung lavage, respiratory system compliance and functional residual capacity were measured. Additionally, central arterial pressure, central venous pressure, heart rate, arterial blood gas, and pulse oximetric saturation were recorded. Lung lavage significantly lowered respiratory system compliance (static as well as specific compliance) and worsened ventilation perfusion matching as evidenced by an increase in Paco2 and a decreased arterial to alveolar oxygen ratio. With increasing mean airway pressures, static/specific compliance improved and then peaked before declining, functional residual capacity increased, and blood gas improved until reaching the flat portion of the pressure-volume relationship of the lung. Optimal gas exchange as reflected by the highest arterial to alveolar oxygen ratio and lowest Paco2 at constant ventilation was found at a mean airway pressure that maintained the functional residual capacity and static respiratory system compliance at the same level as the preinjury levels ("normalized" functional residual capacity and respiratory system compliance). CONCLUSIONS: These results suggest that specific compliance measurement that incorporates static respiratory system compliance and functional residual capacity during high-frequency oscillatory ventilation can be used to adjust mean airway pressure and achieve "normalized" functional residual capacity, static compliance, and gas exchange. These measurements may provide a simple method to optimize lung volume in a surfactant-deficient patient during high-frequency oscillatory ventilation.