Hepatorenal syndrome in hospitalized patients with chronic liver disease: results from the Nationwide Inpatient Sample 2002-2012.

Hepatorenal syndrome (HRS) is one of the leading causes of hospitalizations in patients with chronic liver disease (CLD). We conducted a retrospective national database study to determine the epidemiology of HRS in hospitalized patients with CLD. Data from a Nationwide Inpatient Sample were extracted from 2002 to 2012 using ICD-9-CM codes related to CLD and HRS. The following outcomes were examined: in-hospital mortality, total charges, length of stay (LOS), patient demographics, procedures, complications, and comorbidities. Statistical analysis including regression was performed to examine factors associated with HRS. During 2002-2012, hospital discharges related to CLD increased from 407,246 to 836,475 with an increase of 37.9% for HRS as a complication in this population. Patients with CLD and HRS had worse outcomes compared with patients with CLD without HRS. This was manifested as a higher mortality rate (32.0% vs 10.3%), increased LOS (median 7 vs 5 days), and increased hospital costs (median $16,000 vs $11,000). Logistic regression demonstrated that HIV/AIDS (adjusted OR 2.9, 95% CI 2.2 to 3.9), pneumonia (aOR 2.8, 95% CI 2.3 to 3.2), and esophageal variceal bleeding (aOR 1.9, 95% CI 1.7 to 2.0) were associated with higher mortality in patients with HRS. Conversely, liver transplantation (aOR 0.1, 95% CI 0.1 to 0.1), transjugular intrahepatic portosystemic shunt (aOR 0.5, 95% CI 0.4 to 0.6), and hospitalization in the Midwest region of the USA (aOR 0.7, 95% CI 0.6 to 0.7) were associated with reduced mortality. The incidence of HRS in hospitalized patients with CLD increased during 2002-2012. HRS is associated with significant mortality and morbidity in these patients.

Outcomes of Clostridium difficile infection in pediatric solid organ transplant recipients.

BACKGROUND: The incidence of Clostridium difficile infection (CDI) is increasing in the pediatric population. Pediatric recipients of solid organ transplantation (SOT) may be at a higher risk for CDI in part because of chemotherapy and prolonged hospitalization. METHODS: We utilized data from the Healthcare Cost and Utilization Project Kids' Inpatient Database to study the incidence and outcomes related to CDI as a complicating factor in pediatric recipients of SOT. RESULTS: Our results demonstrate that hospitalized children with SOT have increased rates of infection, with the greatest risk for younger children with additional comorbidities and severe illness. The type of transplanted organ affects the risk for CDI, with the lowest incidence observed in renal transplant patients. CONCLUSION: The occurrence of CDI in the pediatric SOT population contributes to a greater length of stay and higher hospital charges. However, CDI is not an independent predictor of increased in- hospital mortality in these patients.

Increasing the Number of Organ Transplants in the United States by Optimizing Donor Authorization Rates.

While recent policies have focused on allocating organs to patients most in need and lessening geographic disparities, the only mechanism to increase the actual number of transplants is to maximize the potential organ supply. We conducted a retrospective cohort study using OPTN data on all "eligible deaths" from 1/1/08 to 11/1/13 to evaluate variability in donor service area (DSA)-level donor authorization rates, and to quantify the potential gains associated with increasing authorization rates. Despite adjustments for donor demographics (age, race/ethnicity, cause of death) and geographic factors (rural/urban status of donor hospital, statewide participation in deceased-donor registries) among 52 571 eligible deaths, there was significant variability (p < 0.001) in donor authorization rates across the 58 DSAs. Overall DSA-level adjusted authorization rates ranged from 63.5% to 89.5% (median: 72.7%). An additional 773-1623 eligible deaths could have been authorized, yielding 2679-5710 total organs, if the DSAs with authorization rates below the median and 75th percentile, respectively, implemented interventions to perform at the level of the corresponding reference DSA. Opportunities exist within the current organ acquisition framework to markedly improve DSA-level donor authorization rates. Such initiatives would mitigate waitlist mortality while increasing the number of transplants.

Microwave ablation of a large renal aspergilloma.

Increasing numbers of immunocompromised patients have led to a corresponding rise in the incidence of invasive Aspergillus infections. Despite advances in antifungal therapy coupled with reduction in immunosuppression, invasive aspergillosis is associated with significant morbidity and mortality. Although surgical debulking has proven effective in difficult-to-treat cases, patient comorbidities may prevent such intervention. Non-invasive alternatives to surgery are needed. Microwave ablation has many advantages over other ablative techniques, including convection profile, faster heating time, and higher intra-lesion temperatures, which may be associated with greater therapeutic efficacy. We report a case of microwave ablation as an adjunct to medical therapy in angioinvasive renal aspergilloma.

Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome.

BACKGROUND AND AIMS: Teduglutide, a GLP-2 analogue, may restore intestinal structural and functional integrity by promoting repair and growth of the mucosa and reducing gastric emptying and secretion, thereby increasing fluid and nutrient absorption in patients with short bowel syndrome (SBS). This 24-week placebo-controlled study evaluated the ability of teduglutide to reduce parenteral support in patients with SBS with intestinal failure. METHODS: In 83 patients randomised to receive subcutaneous teduglutide 0.10 mg/kg/day (n = 32), 0.05 mg/kg/day (n = 35) or placebo (n = 16) once daily, parenteral fluids were reduced at 4-week intervals if intestinal fluid absorption (48 h urine volumes) increased ≥ 10%. Responders were subjects who demonstrated reductions of ≥ 20% in parenteral volumes from baseline at weeks 20 and 24. The primary efficacy end point, a graded response score (GRS), took into account higher levels and earlier onset of response, leading to longer duration of response. The intensity of the response was defined as a reduction from baseline in parenteral volume (from 20% to 100%), and the duration of the response was considered the response at weeks 16, 20 and 24. The results were tested according to a step-down procedure starting with the 0.10 mg/kg/day dose. RESULTS: Using the GRS criteria, teduglutide in a dose of 0.10 mg/kg/day did not have a statistically significant effect compared with placebo (8/32 vs 1/16, p=0.16), while teduglutide in a dose of 0.05 mg/kg/day had a significant effect (16/35, p = 0.007). Since parenteral volume reductions were equal (353 ± 475 and 354 ± 334 ml/day), the trend towards higher baseline parenteral volume (1816 ± 1008 vs 1374 ± 639 ml/day, p=0.11) in the 0.10 mg/kg/day group compared with the 0.05 mg/kg/day group may have accounted for this discrepancy. Three teduglutide-treated patients were completely weaned off parenteral support. Serious adverse events were distributed similarly between active treatment groups and placebo. Villus height, plasma citrulline concentration and lean body mass were significantly increased with teduglutide compared with placebo. CONCLUSIONS: Teduglutide was safe, well tolerated, intestinotrophic and suggested pro-absorptive effects facilitating reductions in parenteral support in patients with SBS with intestinal failure. ClinicalTrials.gov number NCT00172185.

Predicting outcome of procedures to slow intestinal transit.

Procedures designed to slow intestinal transit in patients with the short-bowel syndrome (SBS) have unpredictable outcomes. Our aim was to evaluate the outcome and predictive factors for this complication in SBS patients. Ten patients (37-61 years) underwent reversed segment (n = 9) or nipple valve creation (n = 1). All patients had remnant lengths over 90 cm and rapid intestinal transit times. All subjects had benign diseases, including Crohn's (n = 3). Six patients had a colon remnant. SBS had been present for 8 to 150 months. Nine (90%) required parental nutrition (PN) preoperatively. A procedure was performed either alone (n = 5) or concurrently with an ostomy closure (n = 3), an ostomy revision (n = 1), or a fundoplication (n = 1). There was one postoperative complication (urinary tract infection) and no deaths. Two patients developed bacterial overgrowth. One required repair of an ileocolonic stricture. One reversed segment was taken down 12 months later. Five (50%) patients improved (off PN), five remained on PN or had persistent diarrhea. Patients with a successful outcome were more likely to have had ostomy takedown (60% vs 0%). The duration of SBS; presence of Crohn's disease, a colon remnant, or type 1 anatomy; and the transit times were similar in both groups. Adjusted remnant length (small intestine +30 cm for type 2 anatomy and +60 cm for type 3) was similar (136 +/- 20 vs 154 +/- 25 cm). Procedures may benefit half of selected SBS patients with adequate remnant length and rapid transit. Successful patients are more likely to have an ostomy takedown, but the outcome is less determined by transit time or intestinal length if over 90 cm.

Histoplasmosis in solid organ transplant recipients at a large Midwestern university transplant center.

Histoplasma capsulatum sporadically causes severe infections in solid organ transplant (SOT) patients in the Midwest, but it has been an unusual infection among those patients followed at the University of Nebraska Medical Center (UNMC), located at the western edge of the 'histo belt.' Nine SOT patients with histoplasmosis are described (6 renal or renal-pancreas and 3 liver recipients) who developed severe histoplasmosis over a recent 2.5-year period at UNMC. Symptoms started a median of 11 months (range, 1.2-90 months) after organ transplant and consisted primarily of fever, cough, shortness of breath, and malaise or fatigue present for approximately 30 days prior to medical evaluation. All patients had an abnormal chest radiograph and/or computed tomographic scan. Tacrolimus was the main immunosuppressant in all 9 patients, along with prednisone or mycophenolate. Dacluzimab or thymoglobulin had been given around the time of transplant in 6 of 9. None was treated for an episode of acute rejection within 2 months before onset of histoplasmosis, although 2 were on high-dose immunosuppression after recent transplants. Diagnosis was made by culture in 8 of the 9 patients, with positive serum and urine histoplasma antigen tests in all 9 cases. From 1997 to 2001, during a period of relative quiescence of the disease in the general population, the rate of clinical histoplasmosis among SOT patients at UNMC was estimated at 0.11%, whereas during 2002 through the first half of 2004, the rate rose 17-fold to 1.9%. Histoplasmosis can present as a prolonged febrile illness with subacute pulmonary symptoms in a cohort of SOT patients, despite the absence of a regional outbreak.

Pegylated interferon for recurrent hepatitis C in liver transplant recipients with renal failure: a prospective cohort study.

BACKGROUND: Hepatitis C (HCV) universally recurs following orthotopic liver transplantation (OLT), representing an important cause for retransplantation. Although it is often treated with interferon and ribavirin, ribavirin is contraindicated in the presence of renal failure. In this setting of renal failure, pegylated-interferon monotherapy may be useful for recurrent HCV in liver transplant patients. METHODS: Between June 2001 and November 2002, patients with recurrent HCV were screened to determine if they were eligible for treatment. Renal failure was defined as serum creatinine greater than 1.8 mg/dL. HCVRNA and liver biopsies were performed prior to treatment, end of treatment (EOT) and 6 months after EOT for those who were HCV-RNA negative at EOT. Patients were followed prospectively after starting weekly pegylated-interferon alpha 2b 1.0 microg/kg (Schering-Plough, Kenilworth, NJ, USA). RESULTS: Among the 45 patients with recurrent HCV screened, 9 were eligible, including 8 men and 1 woman of average age 55 years. Eight patients were intolerant to the treatment requiring discontinuation within the first 3 months. Two patients developed a sustained response to HCV eradication. One patient who completed treatment has normal liver tests but is still viremic. CONCLUSIONS: Pegylated-interferon alpha 2b is poorly tolerated in liver transplant recipients with recurrent HCV and chronic renal failure. Larger, prospective studies are required to determine the optimum duration of treatment and the impact of treatment on histology and quality of life.

Lipoatrophic diabetes and end-stage liver disease secondary to nonalcoholic steatohepatitis with recurrence after liver transplantation.

BACKGROUND: Lipoatrophic diabetes is an insulin resistance syndrome characterized by the complete or partial lack of adipose tissue and disturbances in lipid and glucose metabolism. Nonalcoholic steatohepatitis (NASH) is a well-described change in liver pathology consisting of steatosis, hepatitis, and fibrosis that can be associated with lipoatrophic diabetes. RESULTS: This article describes the first reported case of lipoatrophic diabetes with NASH leading to liver failure and liver transplantation. Before transplantation, the patient required 600-700 U of insulin/day. After transplantation, a dramatic decline in her insulin requirements was observed, despite corticosteroids. Eighteen months after transplantation, her glycemic control worsened, and she developed recurrent NASH on serial liver biopsies. CONCLUSIONS: NASH associated with lipoatrophic diabetes can recur after liver transplantation, and in this case, was accompanied by increased insulin requirements. These results suggest that the development of NASH itself may contribute to the insulin resistance observed in lipoatrophic diabetes.

Confirmation of the role of the Mayo Risk Score as a predictor of resource utilization after orthotopic liver transplantation for primary biliary cirrhosis.

Resource utilization is an important consideration when patients are selected for orthotopic liver transplantation (OLT). The Mayo Risk Score has been proposed to help predict optimum time for OLT. We assessed the relation between Mayo risk score, Child-Pugh score, and resource utilization and outcome after OLT for primary biliary cirrhosis. The mean Mayo risk score was greater in patients who died than in the survivors (8.6 +/- 1.4 v 7.1 +/- 1.8; P <.05). There was a positive correlation between Mayo risk score and the 4 resource variables studied (intraoperative blood requirements, time ventilated, and duration of intensive care unit and hospital stays). Patients with a Mayo risk score greater than 7.8 used almost twice the resources of patients with a risk score less than 7.8. A positive correlation also existed between Child-Pugh score and duration of hospital stay. The mean Child-Pugh score in patients who died was greater than that in survivors (10.7 +/- 2.0 v 8.5 +/- 2.8, P =.03). This study confirms that Mayo Risk score is an important predictor of resource utilization and outcome after OLT.

Liver and small bowel transplantation: therapeutic alternatives for the treatment of liver disease and intestinal failure.

Intestinal transplantation is an established life-saving therapy for parenteral nutrition dependent patients suffering from severe complications of parenteral nutrition. Improvements in outcomes over the last decade have occurred with refinements in surgical technique, better immunosuppressive regimens, and clinical experience. The long-term results of intestinal transplantation are not well known and morbidity remains an important obstacle to wider application of this procedure to patients with short bowel syndrome (SBS). This article reviews the indications for intestinal transplantation, the evaluation of potential candidates, therapeutic considerations, postoperative management and common complications experienced by the recipients.

Syntheses of 5'-substituted analogues of carbocyclic 3-deazaadenosine as potential antivirals.

Various 5'-substituted derivatives (2, 3, 6a, 6b, 9a, 9b, 12, 13b, and 15) of carbocyclic 3-deazaadenosine (3-deaza CAdo, 1) were prepared from 3-deaza CAdo (1) and evaluated as antiviral agents against a number of viruses, including HIV-1. Several of the compounds had moderate to good antiviral activity against vaccinia (VV) and vesicular stomatitis (VSV) viruses; however, the antiviral activity of the analogues did not exceed that of the parent compound. No anti-HIV activity was detected.

Postischemic hypoperfusion during unilateral lung reperfusion in vivo.

The incomplete restoration of blood flow during reperfusion may amplify injury by prolonging ischemia; this "no-reflow" has been studied extensively in systemic organs. Our goal was to examine lung blood flow and microvascular function, specifically to determine whether blood flow is altered during lung reperfusion injury in vivo. In a unilateral lung model of ischemia-reperfusion in awake sheep, we measured pulmonary vascular resistance in each lung by radiolabeled microspheres. Measurements were made before 14 h of ischemia and again 4 h after reperfusion. Vascular resistance in the reperfused lung increased 3-fold (9.64 +/- 0.85 to 27.04 +/- 4.73 cm H2O/L/min) during reperfusion. The increase in vascular resistance in the reperfused lung fully accounted for the small increase in overall pulmonary vascular resistance (4.04 +/- 0.26 to 5.52 +/- 0.70 cm H2O/L/min). Microvascular permeability in the reperfused lung increased 52% more than in the contralateral lung, measured by an improved indicator dilution method with additional markers sensitive to surface area (butanediol). We conclude that changes in vascular resistance and microvascular function occur during lung reperfusion injury in vivo. The demonstration that postischemic hypoperfusion occurs during lung reperfusion in vivo suggests possible new avenues of approach to related clinical disorders.

Lung ischemia-reperfusion injury in awake sheep: protection with verapamil.

We caused unilateral lung ischemia-reperfusion injury in awake sheep by simultaneously occluding the left pulmonary artery and left main stem bronchus for 12 h. The occluded left lung was inflated with nitrogen. Reperfusion resulted in an elevation of lung lymph flow from 1.3 to 5.0 ml/15 min and an increase in lymph-to-plsma protein concentration ratios. Reperfusion, but not ischemia alone, caused an increase in wet-to-dry weight ratios in both the reperfused left lung and the contralateral right lung. Granulocytes increased in both lungs during the ischemic period and after reperfusion, and hypoxemia developed after reperfusion. The calcium channel antagonist, verapamil, given just before reperfusion, caused a marked attenuation in the reperfusion-induced changes in the lung lymph variables and wet-to-dry weight ratio. However, verapamil did not affect the hypoxemia or granulocyte sequestration seen after reperfusion. We conclude that reperfusion of ischemic sheep lung results in increased microvascular permeability that can be partially prevented by verapamil.

Pulmonary veno-occlusive disease. Fatal progression of pulmonary hypertension despite steroid-induced remission of interstitial pneumonitis.

This report describes a 28-yr-old patient with pulmonary veno-occlusive disease (PVOD). She presented with pulmonary hypertension, hypoxemia, and interstitial pneumonitis. We report the discordance between the response of her hypoxemia and interstitial pneumonitis, which resolved with corticosteroid therapy, and her progressive pulmonary hypertension, which caused fatal right heart failure. This report emphasizes that the radiographic interstitial shadowing of PVOD may be caused by either (1) an inflammatory interstitial pneumonitis (which may be responsive to anti-inflammatory therapy) or (2) interstitial pulmonary edema, or both.

Rib cage and abdominal volume displacements during breathing in pregnancy.

To examine the effect of abdominal distension upon the actions of both rib cage and abdomen, we made serial determinations of tidal volume with a chest wall volume-displacement method in 8 pregnant women. Enhancement of tidal volume, long recognized in pregnancy, was achieved usually by augmentation of rib cage volume displacement. By contrast, abdominal volume displacement during quiet breathing is not altered in a predictable fashion by the gravid state. Given these findings, we hypothesize that the increased diaphragmatic contraction of pregnancy is accompanied by the transmission of that force to the lower rib cage via the area of apposition and that diaphragmatic contraction accounts for enhancement of the tidal breath. Diminished abdominal compliance might contribute to the augmentation of rib cage volume displacement as well. Konno-Mead diagrams suggest that this hypothesis is true in some, but not all, subjects.

Relation of mouth flow to body surface flow during forced oscillation at the chest.

We have investigated the body surface flow/mouth flow transfer function (magnitude ratio and phase difference) in seven healthy male subjects driven at the chest from 4 to 30 Hz. The measurements were performed with a specially designed plethysmograph and analyzer. The subjects were driven with a mechanical oscillator placed on the sternum. After differences in gas temperature and humidity were taken into account, the data were in agreement up to 15 Hz with a simple second-order model including an airway compartment, with a resistance and an inertance, and a shunt compliance representing alveolar gas. At larger frequencies, closer inspection revealed that a third-order model was optimal. We interpret these results as indicating a compartmentalization of gas compliance within the thorax, communicating via a resistive element. Airway inertance did not seem to be distributed.

Respiratory mechanical effects of abdominal distension.

We develop a theory to predict the partitioning of a change in volume of the abdominal contents into the end-expiratory volume changes of the lung, rib cage, and anterior abdominal wall. First, we calculate the distribution of such a volume change using the relative compliances of the three compartments. We then consider the inspiratory influence of abdominal pressure on the rib cage and its effect on the distribution of this volume. We test our theory by inducing gastric distension in three experienced laboratory personnel. We instilled and subsequently withdrew 1 liter of water from a gastric balloon and examined the effects of this change in gastric volume on the relaxation characteristics of the respiratory system. The distribution of the volume change that would be expected from the observed relative compliances of the three compartments would be approximately 66% into change in lung volume, 25% into change in rib cage volume, and 9% into change in abdominal volume. Instead, in line with our predictions for acute gastric distension, approximately 33% went into decrease in lung volume, 40% into increase in rib cage volume, and 26% into increase in abdominal volume. These results suggest that the interactions among the rib cage, abdomen, and diaphragm are such as to defend against large changes in end-expiratory lung volume in the face of abdominal distension.