Uncommon Yet Noteworthy: A Clear and Comprehensive Case Report on Pediatric Hip Dislocation.

Introduction: Children, especially those under the age of five, seldom get hip dislocations. Young children may sustain dislocations from minor accidents such as slips or falls from low heights, whereas adolescents typically do so from high-intensity events such as car crashes or collision sports. Posterior dislocation occurs 8-9 times more frequently than those in the anterior. Here, we describe about the acute posterior hip dislocation suffered by a 5-year-old boy in this case report. Case Report: A 5-year-old girl reported to ER with left hip pain and difficulty to walk after slipping and falling while playing football at home. About 90 min after the fall, she presented at the hospital. The injured hip showed internal rotation, adduction, and flexion. An immediate pelvis X-ray revealed a right hip posterior dislocation. Under intravenous anesthesia, the dislocation was successfully reduced utilizing the Allis technique in the emergency room 3 h after the accident. Post-reduction radiographs verified that the reduction was successful. After 15 days of immobilization and 2 weeks of bilateral skin traction, the youngster was able to resume full weight-bearing walking with excellent tolerance. Conclusion: To reduce the risk of avascular necrosis (AVN), pediatric hip dislocations require prompt reduction within 6 h. Soft-tissue injuries are found using post-reduction magnetic resource imaging. AVN requires constant observation for at least 2 years. Since traumatic hip dislocations in children under the age of five are rare, prompt diagnosis and treatment are essential.

Beating the Odds: A Full-Term Delivery After Liver Transplantation of a Pregnant Hyperthyroid Patient at 19 Weeks' Gestation for Propylthiouracil-Induced Acute Liver Failure.

Liver transplantation (LT) for acute liver failure is an uncommon occurrence in the setting of pregnancy given the risk of fetal demise, and rarely is it undertaken with a viable fetus. Maternal hyperthyroidism increases fetal risk in the setting of LT, particularly in the setting of thyrotoxicosis. We report the first case of propylthiouracil-induced acute liver failure in a hyperthyroid patient in her second trimester resulting in LT. The multidisciplinary management led to a favorable outcome for the patient and the subsequent delivery of a healthy infant at 38-weeks' gestation.

Utility of Tolvaptan in the Perioperative Management of Severe Hyponatremia During Liver Transplantation: A Case Report.

Severe hyponatremia can complicate the pretransplantation management of patients with decompensated cirrhosis while they await liver transplantation. Before the liver transplant, it is critical to correct severe hyponatremia to an appropriate level to reduce the risks of perioperative complications such as central pontine myelinolysis, cerebral edema, and seizures. Vasopressin receptor antagonists, and in particular tolvaptan, offer a therapeutic modality that can correct severe refractory hyponatremia in a timely and predictable manner before liver transplantation. In this case report, we describe a patient with decompensated cirrhosis and severe hyponatremia in whom administration of tolvaptan led to an optimal correction of preoperative severe hyponatremia and allowed for successful liver transplantation with no associated postoperative complications. In light of the increasing pretransplantation disease severity and higher risk of severe hyponatremia, the use of tolvaptan in the pretransplant period may gain increasing importance as a therapeutic intervention for maintaining peritransplant sodium homeostasis.

The Natural History of Severe Acute Liver Injury.

OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death. METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × elevated (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol, APAP) ALI, or INR≥2.0, ALT≥10x elevated, and bilirubin≥3.0 mg/dl for non-APAP ALI, both groups without any discernible HE. Subjects who progressed to poor outcomes (ALF, death, LT) were compared, by univariate analysis, with those who recovered. A model to predict poor outcome was developed using the random forest (RF) procedure. RESULTS: Progression to a poor outcome occurred in 90/386 (23%), primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of whom had a poor outcome). Of 82 variables entered into the RF procedure: etiology, bilirubin, INR, APAP level and duration of jaundice were the most predictive of progression to ALF, LT, or death. CONCLUSIONS: A majority of ALI cases are due to APAP, 93% of whom will improve rapidly and fully recover, while non-APAP patients have a far greater risk of poor outcome and should be targeted for early referral to a liver transplant center.

Acute Kidney Injury in Cirrhosis: Baseline Serum Creatinine Predicts Patient Outcomes.

OBJECTIVES: The International Ascites Club (IAC) recently defined Stage 1 acute kidney injury (AKI) for cirrhosis as an acute increase in serum creatinine (SCr) by ≥0.3 mg/dl or by ≥50% in <48 h from a stable value within 3 months. The baseline SCr may influence AKI risk and patient outcomes. The objective of this study is to determine in cirrhosis whether the baseline SCr has any effect on the in-hospital AKI course and patient survival. METHODS: North American Consortium for the Study of End-Stage Liver Disease is a consortium of tertiary-care hepatology centers prospectively enroling non-elective cirrhotic inpatients. Patients with different baseline SCr levels (≤0.5, 0.51-1.0, 1.01-1.5, >1.5 mg/dl) were evaluated for the development of AKI, and compared for AKI outcomes and 30-day survival. RESULTS: 653 hospitalized cirrhotics (56.7±10years, 64% men, 30% with infection) were included. The incidence of AKI was 47% of enrolled patients. Patients with higher baseline SCr were more likely to develop AKI, with significantly higher delta and peak SCr (P<0.001) than the other groups, more likely to have a progressive AKI course (P<0.0001), associated with a significantly reduced 30-day survival (P<0.0001). Multivariate logistic regression showed that the delta SCr during an AKI episode to be the strongest factor impacting AKI outcomes and survival (P<0.001), with a delta SCr of 0.70 mg/dl having a 68% sensitivity and 80% specificity for predicting 30-day mortality. CONCLUSIONS: Admitted cirrhotic patients with higher baseline SCr are at higher risk for in-hospital development of AKI, and more likely to have AKI progression with reduced survival. Therefore, such patients should be closely monitored and treated promptly for their AKI.

One Size Does Not Fit All--Regional Variation in the Impact of the Share 35 Liver Allocation Policy.

Allocation policies for liver transplantation underwent significant changes in June 2013 with the introduction of Share 35. We aimed to examine the effect of Share 35 on regional variation in posttransplant outcomes. We examined two patient groups from the United Network for Organ Sharing dataset; a pre-Share 35 group composed of patients transplanted between June 17, 2012, and June 17, 2013 (n = 5523), and a post-Share group composed of patients transplanted between June 18, 2013, and June 18, 2014 (n = 5815). We used Kaplan-Meier and Cox multivariable analyses to compare survival. There were significant increases in allocation Model for End-stage Liver Disease (MELD) scores, laboratory MELD scores, and proportions of patients in the intensive care unit and on mechanical, ventilated, or organ-perfusion support at transplant post-Share 35. We also observed a significant increase in donor risk index in this group. We found no difference on a national level in survival between patients transplanted pre-Share 35 and post-Share 35 (p = 0.987). Regionally, however, posttransplantation survival was significantly worse in the post-Share 35 patients in regions 4 and 10 (p = 0.008 and p = 0.04), with no significant differences in the remaining regions. These results suggest that Share 35 has been associated with transplanting "sicker patients" with higher MELD scores, and although no difference in survival is observed on a national level, outcomes appear to be concerning in some regions.

The use of transtracheal oxygen therapy in the management of severe hepatopulmonary syndrome after liver transplantation.

Hepatopulmonary syndrome (HPS) is a unique form of hypoxemia found in patients who have chronic liver disease. The definitive treatment for HPS is liver transplantation (LT), with resolution of hypoxemia occurring weeks to months after LT. Because there has been an increase in the use of LT to treat severe HPS (PaO2 ≤ 50 mm Hg), alternatives to oxygen administration via nasal cannula (NC) or face mask must be examined to facilitate early postoperative mobilization and to minimize postoperative pulmonary complications. Transtracheal oxygen (TTO) therapy is a practical alternative that has been shown to improve oxygen requirements, facilitate patient mobility, and improve exercise tolerance in advanced lung disease. In this case series, we describe the use of TTO in the management of hypoxemia associated with severe HPS after LT. A transition from NC to TTO resulted in a significant reduction in oxygen requirements, early postoperative mobilization and discharge from the hospital, and a subsequent expedited liberation from supplemental oxygen. This case series emphasizes the potential utility of TTO therapy as an alternative to conventional oxygen delivery modalities in the management of severe HPS after LT.

Diagnostic challenges in the evaluation of hepatic grafts from donors with HELLP syndrome: case report and review of the literature.

HELLP syndrome (hemolysis, elevated liver function tests, low platelets) is a rare complication of pregnancy that can result in severe complications such as hepatic infarction, subcapsular liver hematomas, and maternal brain death from cerebral hemorrhage. Recently, several investigators have described cases of successful transplantation using livers procured from donors who suffered brain death as a result of HELLP syndrome. However, this new class of marginal liver donors must be approached with caution. We report the case of a 28-year-old pregnant woman who suffered brain death due to HELLP syndrome and was subsequently evaluated for potential liver donation. Although her transaminitis and other liver function tests were markedly improving during the final days of her hospital course, her liver demonstrated segments of necrosis during attempted procurement, and the histology revealed extensive centrilobular necrosis. This case suggests that peak values of serum transaminases, as well as partial resolution of transaminitis, appear to have limited predictive ability in determining the suitability of the hepatic graft for transplantation. Thus, donors with HELLP syndrome should be approached with caution, even in the setting of laboratory values suggesting minimal or resolving hepatic injury. Furthermore, there should be an additional emphasis on obtaining and reviewing histology of the potential graft to determine its suitability for transplantation.

Structure-function relationships in side chain lactam cross-linked peptide models of a conserved N-terminal domain of apolipoprotein E.

Bioactive peptides have multiple conformations in solution but adopt well-defined conformations at lipid surfaces and in interactions with receptors. We have used side chain lactam cross-links to stabilize secondary structures in the following peptide models of a conserved N-terminal domain of apolipoprotein E (cross-link periodicity in parentheses): I, H2N-GQTLSEQVQEELLSSQVTQELRAG-COOH (none); III, [sequence; see text] (i to i + 3); IV,[sequence; see text] (i to i + 4); IVa, [sequence, see text] (i to i + 4) (lactams above the sequence, potential salt bridges below the sequence). We previously demonstrated [Luo et al. (1994) Biochemistry 33, 12367-12377; Braddock et al. (1996) Biochemistry 35, 13975-13984] that peptide III, containing lactam cross-links between the i and i + 3 side chains, enhances specific binding of LDL via a receptor other than the LDL-receptor. Peptide III in solution consists of two short alpha helices connected by a non alpha helical segment. Here we examine the hypothesis that the domain modeled by peptide III is one antipode of a conformational switch. To model another antipode of the switch, we introduced two strategic modifications into peptide III to examine structure-function relationships in this domain: (1) the spacing of the lactam cross-links was changed (i to i + 4 in peptides IV and IVa) and (2) peptides IV and IVa contain the two alternative sequences at a site of a possible end-capping interaction in peptide III. The structure of peptide IV, determined by 2D-NMR, is alpha helical across its entire length. Despite the remarkable degree of structural order, peptide IV is biologically inactive. In contrast, peptides III and possibly IVa contain a central interruption of the alpha helix, which appears necessary for biological activity. These and other studies support the hypothesis that this domain is a conformational switch which, to the extent that it models apolipoprotein E itself, may modulate interactions between apo E and its various receptors.

Conformationally specific enhancement of receptor-mediated LDL binding and internalization by peptide models of a conserved anionic N-terminal domain of human apolipoprotein E.

In this paper, we test the hypothesis that peptide models of a highly conserved domain of apolipoprotein E (amino acids 41-60 in human apo E) modulate the binding and internalization of LDL to cell surface receptors in a conformationally specific manner. Three peptides were compared: peptide I containing the natural sequence of amino acids 41-60 of human apo E; peptide III containing side-chain lactam cross-links designed to enhance alpha-helical structure; and peptide II containing cross-links designed to prevent formation of alpha-helices. Peptide III was shown previously to consist of two short alpha-helical domains linked by a turn and to have more alpha-helical content than peptide I, while peptide II was shown to have less helical content than either peptide III or I(Luo et al., 1994). Peptide III induced a 30-fold increase in the specific binding of 125I-LDL to normal human skin fibroblasts and a 60-fold increase in the binding to fibroblasts lacking the LDL-R. This same peptide also restored the binding to normal fibroblasts of 125I-LDL from a patient with familial defective apolipoprotein B, the R3500-->Q mutation. Analysis of binding indicated an increase in the apparent number of binding sites, with little effect on the affinity of 125I-LDL for the cell surface. Heparinase treatment of the cells did not abrogate this effect, suggesting that the increased binding is not mediated by cell surface glycans. LDL internalization but not degradation was also increased by peptide III. Similar but smaller effects were also induced by peptide I. Peptide II was much less active than peptide I or III. Thus, the order of biological activity was the same as the order of alpha-helical content, i.e., peptide III > peptide I > peptide II. These results suggest a hitherto unknown biological function for a highly conserved domain of apolipoprotein E, and this bioactivity was shown by peptide models to be specific to the alpha-helical conformation.

Structural and thermodynamic characterization of a bioactive peptide model of apolipoprotein E: side-chain lactam bridges to constrain the conformation.

Apolipoprotein E plays a critical role in plasma lipoprotein clearance. A peptide model of a highly conserved domain of this protein has been shown to increase low-density lipoprotein binding to fibroblast cell surface receptors. To distinguish between two potential structures--one essentially alpha-helical and nonamphiphilic, the other an amphiphilic pi-helix--synthetic side-chain lactam constraints have been incorporated into model peptides in order to restrict conformational flexibility favoring either the alpha- or pi-helix. Here we provide CD and 1H NMR data suggesting that the more biologically active, putatively alpha-helical peptide indeed contains two alpha-helical domains separated by a central bend. Whereas previous studies (Osapay & Taylor, 1992; Felix et al., 1988) indicated stabilization of alpha-helices by cross-links between the i and i + 4 residues, the current paper demonstrates that cross-links between the i and i + 3 residues also stabilize the helix. Indeed, the stabilization afforded by these cross-links is approximately 1 kcal/mol, similar to that reported for peptides cross-linked between the i and i + 4 residues, and derives exclusively from a loss of entropy of the unfolded state. The presence of the alpha-helical structure appears to correlate well with biological activity. This study provides initial insight into the bioactive structure of this domain of apo E and suggests strategies as to how peptides can be conformationally constrained to enhance their stability and biological function.