Novel Allograft in the Load-Bearing Portion of the Femoral Head.

Background: An osteochondral defect in the hip can be a painful and limiting pathologic process. The damaged joint may progress into premature osteoarthritis, further limiting a patient's functionality. Case Report: A 24-year-old male presented to the clinic with left hip pain. The patient had been involved in a motor vehicle accident 3 years prior to presentation to our clinic. His injury from the high-speed accident required intramedullary rod fixation for a right-sided (contralateral) subtrochanteric femur fracture. The patient complained of left groin pain when in a sitting position, with activities of daily living, and with exercise. He failed conservative management consisting of nonsteroidal anti-inflammatory drugs and physical therapy. Imaging on presentation demonstrated an osteochondral defect in the weight-bearing portion of the left femoral head consistent with an International Cartilage Repair Society grade 4b lesion, a cam lesion was noted on assessment of bone morphology, and magnetic resonance imaging revealed degenerative labral pathology. The patient was treated with surgical hip dislocation through a modified Hardinge approach, femoral head osteochondral allograft transplantation using a Missouri Osteochondral Preservation System (MOPS) graft, acetabuloplasty, femoral neck osteoplasty, and open labral repair. Conclusion: Femoral head osteochondral MOPS allograft transplantation is a viable technique for joint preservation in young patients with posttraumatic osteochondral defects of the femoral head.

Female-specific pancreatic cancer survival from CT imaging of visceral fat implicates glutathione metabolism in solid tumors.

RATIONALE AND OBJECTIVES: To identify if body composition, assessed with preoperative CT-based visceral fat ratio quantification as well as tumor metabolic gene expression, predicts sex-dependent overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This was a retrospective analysis of preoperative CT in 98 male and 107 female patients with PDAC. Relative visceral fat (rVFA; visceral fat normalized to total fat) was measured automatically using software and corrected manually. Median and optimized rVFA thresholds were determined according to published methods. Kaplan Meier and log-rank tests were used to estimate OS. Multivariate models were developed to identify interactions between sex, rVFA, and OS. Unsupervised gene expression analysis of PDAC tumors from The Cancer Genome Atlas (TCGA) was performed to identify metabolic pathways with similar survival patterns to rVFA. RESULTS: Optimized preoperative rVFA threshold of 38.9% predicted significantly different OS in females with a median OS of 15 months (above threshold) vs 24 months (below threshold; p = 0.004). No significant threshold was identified in males. This female-specific significance was independent of age, stage, and presence of chronic pancreatitis (p = 0.02). Tumor gene expression analysis identified female-specific stratification from a five-gene signature of glutathione S-transferases. This was observed for PDAC as well as clear cell renal carcinoma and glioblastoma. CONCLUSION: CT-based assessments of visceral fat can predict pancreatic cancer OS in females. Glutathione S-transferase expression in tumors predicts female-specific OS in a similar fashion.

Can we predict the cardiac benefit of deep inspiration breath hold for left breast and regional nodal irradiation?

PURPOSE: Deep inspiration breath hold (DIBH) is used to decrease the dose of radiotherapy delivered to the heart. There is a need to define criteria to select patients with the potential to derive a real clinical benefit from DIBH treatment. Our study's main goal was to investigate whether two CT-scan cardiac anatomical parameters, cardiac contact distance in the parasagittal plane (CCDps) and lateral heart-to-chest distance (HCD), were predictive of unmet dosimetric cardiac constraints for left breast and regional nodal irradiation (RNI). MATERIALS AND METHODS: This retrospective single-institution dosimetric study included 62 planning CT scans of women with left-sided breast cancer (BC) from 2016 to 2021. Two independent radiation oncologists measured HCD and CCDps twice to assess inter- and intra-observer reproducibility. Dosimetric constraints to be respected were defined, and dosimetric parameters of interest were collected for each patient. RESULTS: Mean heart dose was 7.9Gy. Inter-rater reproducibility between the two readers was considered excellent. The mean heart dose constraint<8Gy was not achieved in 25 patients (40%) and was achieved in 37 patients (60%). There was a significant correlation between mean heart dose and HCD (rs=-0.25, P=0.050) and between mean heart dose and CCDps (rs=0.25, P=0.047). The correlation between HCD and CCDps and unmet cardiac dosimetric constraints was not statistically significant. CONCLUSION: Our dosimetric analysis did not find that the cardiac anatomical parameters HCD and CCDps were predictive of unmet dosimetric cardiac constraints, nor that they were good predictors for cardiac exposure in left-sided BC radiotherapy comprising RNI.

Comparison between the HyperArc™ technique and the CyberKnife® technique for stereotactic treatment of brain metastases.

PURPOSE: The purpose of this study was to compare the planimetric capacities between HyperArc™-based stereotactic radiosurgery and robotic radiosurgery system-based planning using CyberKnife® M6 for single and multiple cranial metastases. MATERIALS AND METHODS: We evaluated 51 treatment plans for cranial metastases, including 30 patients with a single lesion and 21 patients with multiple lesions, treated with the CyberKnife® M6. These treatment plans were optimized using the HyperArc™ (HA) system with the TrueBeam. The comparison of the quality of the treatment plans between the two treatment techniques (CyberKnife and HyperArc) was performed using the Eclipse treatment planning system. Dosimetric parameters were compared for target volumes and organs at risk. RESULTS: Coverage of the target volumes was equivalent between the two techniques, whereas median Paddick conformity index and median gradient index for all target volumes were 0.9 and 3.4, respectively for HyperArc plans, and 0.8 and 4.5 for CyberKnife plans (P<0.001). The median dose of gross tumor volume (GTV) for HyperArc and CyberKnife plans were 28.4 and 28.8, respectively. Total brain V18Gy and V12Gy-GTVs were 11cm3 and 20.2cm3 for HyperArc plans versus 18cm3 and 34.1cm3 for CyberKnife plans (P<0.001). CONCLUSION: The HyperArc provided better brain sparing, with a significant reduction in V12Gy and V18Gy, associated with a lower gradient index, whereas the CyberKnife gave a higher median GTV dose. The HyperArc technique seems to be more appropriate for multiple cranial metastases and for large single metastatic lesions.

Chemoselective formation of cyclo-aliphatic and cyclo-olefinic 1,3-diols via pressure hydrogenation of potentially biobased platform molecules using Knölker-type catalysts.

The hydrogenative conversions of the biobased platform molecules 4-hydroxycyclopent-2-enone and cyclopentane-1,3-dione to their corresponding 1,3-diols are established using a pre-activated Knölker-type iron catalyst. The catalyst exhibits a high selectivity for ketone reduction, and does not induce dehydration. Moreover, by using different substituents of the ligand, the cis-trans ratio of the products can be affected substantially. A decent compatibility of this catalytic system with various structurally related substrates is demonstrated.

Hydrogenation of Cyclic 1,3-Diones to Their 1,3-Diols Using Heterogeneous Catalysts: Toward a Facile, Robust, Scalable, and Potentially Bio-Based Route.

Cyclopentane-1,3-diol (4b) has gained renewed attention as a potential building block for polymers and fuels because its synthesis from hemicellulose-derived 4-hydroxycyclopent-2-enone (3) was recently disclosed. However, cyclopentane-1,3-dione (4), which is a constitutional isomer of 3, possesses a higher chemical stability and can therefore afford higher carbon mass balances and higher yields of 4b in the hydrogenation reaction under more concentrated conditions. In this work, the hydrogenation of 4 into 4b over a commercial Ru/C catalyst was systematically investigated on a bench scale through kinetic studies and variation of reaction conditions. Herein, the temperature, H2-pressure, and the solvent choice were found to have significant effects on the reaction rate and suppression of undesired dehydration of 4. The cis-trans ratio of 4b is naturally generated as 7:3 in these reactions. However, at elevated reaction temperatures, 4b epimerizes, yielding more trans products. This effect was also studied and rationalized from a thermodynamic perspective using DFT. The combined optimized reaction conditions provided 78% yield for 4b, and successful applications to 8-fold scaled up reactions (40 g) and a substrate scope of several 1,3-diones demonstrate the general applicability of this catalytic approach.

Atrial Fibrillation and the Prognostic Performance of Biomarkers in Heart Failure.

BACKGROUND: Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended, but the influence of atrial fibrillation (AF) on prognostic performance of many markers is unclear. We investigated the influence of AF on the prognostic performance of circulating biomarkers in HF. METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide, C-type natriuretic peptide (CNP), NT-proCNP, high-sensitivity troponin-T, high-sensitivity troponin-I, mid-regional-propeptide adrenomedullin, co-peptin, growth differentiation factor-15, soluble Suppressor of Tumorigenicitiy (sST2), galectin-3, and procalcitonin plasma concentrations were measured in a prospective, multicenter study of adults with HF. AF was defined as a previous history of AF, and/or presence of AF/flutter on baseline 12-lead electrocardiogram. The primary outcome was the composite of HF-hospitalization or all-cause mortality at 2 years. RESULTS: Among 1099 patients (age 62 ± 12years, 28% female), 261(24%) patients had AF. Above-median concentrations of all biomarkers were independently associated with increased risk of the primary outcome. Significant interactions with AF were detected for galectin-3 and sST2. In considering NT-proBNP for additive risk stratification, sST2 (adjusted hazard ratio [AHR]1.85, 95%confidence interval [C.I.] 1.17-2.91) and galectin-3 (AHR1.85, 95%C.I. 1.09-2.45) were independently associated with increased primary outcome only in the presence of AF. The prognostic performance of sST2 was also stronger in AF for all-cause mortality (AF: AHR2.82, 95%C.I. 1.26-6.21; non-AF: AHR1.78, 95% C.I. 1.14-2.76 without AF), while galectin-3 predicted HF-hospitalization only in AF (AHR1.64, 95%C.I. 1.03-2.62). CONCLUSIONS: AF modified the prognostic utility of selected guideline-endorsed HF-biomarkers. Application of markers for prognostic purposes in HF requires consideration of the presence or absence of AF. CLINICAL TRIAL REGISTRATION: ACTRN12610000374066.

Contrasting biogeographical patterns in Margarella (Gastropoda: Calliostomatidae: Margarellinae) across the Antarctic Polar Front.

Members of the trochoidean genus Margarella (Calliostomatidae) are broadly distributed across Antarctic and sub-Antarctic ecosystems. Here we used novel mitochondrial and nuclear gene sequences to clarify species boundaries and phylogenetic relationships among seven nominal species distributed on either side of the Antarctic Polar Front (APF). Molecular reconstructions and species-delimitation analyses recognized only four species: M. antarctica (the Antarctic Peninsula), M. achilles (endemic to South Georgia), M. steineni (South Georgia and Crozet Island) and the morphologically variable M. violacea (=M. expansa, M. porcellana and M. pruinosa), with populations in southern South America, the Falkland/Malvinas, Crozet and Kerguelen Islands. Margarella violacea and M. achilles are sister species, closely related to M. steineni, with M. antarctica sister to all these. This taxonomy reflects contrasting biogeographic patterns on either side of the APF in the Southern Ocean. Populations of Margarella north of the APF (M. violacea) showed significant genetic variation but with many shared haplotypes between geographically distant populations. By contrast, populations south of the APF (M. antarctica, M. steineni and M. achilles) exhibited fewer haplotypes and comprised three distinct species, each occurring across a separate geographical range. We hypothesize that the biogeographical differences may be the consequence of the presence north of the APF of buoyant kelps - potential long-distance dispersal vectors for these vetigastropods with benthic-protected development - and their near-absence to the south. Finally, we suggest that the low levels of genetic diversity within higher-latitude Margarella reflect the impact of Quaternary glacial cycles that exterminated local populations during their maxima.

Patellofemoral Arthroplasty.

BACKGROUND: Patellofemoral arthritis is a common cause of anterior knee pain and limits flexion-related activities of daily living and exercise. While frequently present in bicompartmental and tricompartmental osteoarthritis, patellofemoral arthritis can occur in isolation. Patellofemoral arthroplasty as a treatment option is gaining in popularity, especially with new implant designs. We report a case in which new inlay implants were used to resurface the patellofemoral joint in a patient with contralateral compromise secondary to a previous below-knee amputation. CASE REPORT: A 37-year-old female with a contralateral right below-knee amputation and progressive left patellofemoral arthritis had failed multiple conservative treatment modalities. She underwent isolated patellofemoral arthroplasty using an inlay-designed implant. The patient was followed for 2 years postoperatively. She noticed an immediate increase in her knee range of motion and her pain scores improved. Two years postoperatively, she demonstrated drastic improvement in all outcome measures: International Knee Documentation Committee score (16.1 to 88.5), Lysholm Knee Scoring Scale (22 to 100), Knee Injury and Osteoarthritis Outcome Score (KOOS) Symptoms (7.14 to 96.43), KOOS Pain (2.78 to 100), KOOS Activities of Daily Living (0 to 100), KOOS Sports (0 to 100), and KOOS Quality of Life (12.5 to 93.75). CONCLUSION: Inlay patellofemoral arthroplasty is a valid treatment option for isolated patellofemoral arthritis. Successful results can be achieved with this procedure after failure of conservative measures in patients with limited or no evidence of tibiofemoral arthritis.

Synergy of Sex Differences in Visceral Fat Measured with CT and Tumor Metabolism Helps Predict Overall Survival in Patients with Renal Cell Carcinoma.

Purpose To determine if sex differences in abdominal visceral fat composition, measured by using computed tomography (CT), and tumor glucose metabolism, measured by gene expression, can help predict outcomes in patients with clear cell renal cell carcinoma (RCC). Materials and Methods This retrospective cohort study included 222 patients with clear cell RCC from The Cancer Imaging Atlas. By using CT, body fat was segmented into subcutaneous fat and visceral fat areas (VFAs) and normalized to total fat to obtain the relative VFA (rVFA) and relative subcutaneous fat area. Multivariate Cox proportional hazard regression models were performed to identify effects of rVFA on sex-specific survival. Expression profiles for 39 glycolytic genes in tumors from these patients were obtained from The Cancer Genome Atlas to determine sex differences in metabolism and compared with rVFA. Key mutations in clear cell RCC were analyzed for association with rVFA and tumor glycolytic profiles. Results Women with rVFA greater than 30.9% had an increased risk of death (hazard ratio, 3.66 [95% confidence interval: 1.64, 8.19]) for women vs 1.13 ([95% confidence interval: 0.58, 2.18] for men, P = .028). Glycolytic gene expression stratified both men and women, and the combination of low rVFA and low glycolysis identified 19 women with excellent overall survival (P < .001). SETD2 and BAP1 mutations were uniquely enriched in female tumors with high glycolysis (P = .036 and .001, respectively). No significant differences were identified in tumor mutations between patients with high and low rVFA. Conclusion Sex differences in visceral fat and tumor glucose metabolism may provide a new risk-stratification system for patients with clear cell RCC. © RSNA, 2018 Online supplemental material is available for this article.

Urinary hypoxia: an intraoperative marker of risk of cardiac surgery-associated acute kidney injury.

Background: Acute kidney injury (AKI) is common after cardiac surgery and profoundly affects postoperative mortality and morbidity. There are no validated methods to assess risk of AKI intraoperatively. Methods: We determined the association between postoperative AKI and intraoperative urinary oxygen tension (PO2), measured via a fiber optic probe in the tip of the urinary catheter, in 65 patients undergoing high-risk cardiac surgery requiring cardiopulmonary bypass (CPB). AKI was diagnosed by modified Kidney Disease: Improving Global Outcomes criteria. Results: Urinary PO2 fell during the operation, often reaching its nadir during rewarming or after weaning from CPB. Nadir urinary PO2 was lower in the 26 patients who developed AKI (mean ± SD, 8.9 ± 5.6 mmHg) than in the 39 patients who did not (14.9 ± 10.2 mmHg, P = 0.008). Patients who developed AKI had longer periods of urinary PO2 ≤15 and 10 mmHg than patients who did not. Odds of AKI increased when urinary PO2 fell to ≤10 mmHg {3.60 [95% confidence interval (CI) 1.27-10.21]} or ≤5 mmHg [3.60 (95% CI 1.04-12.42), P = 0.04] during the operation. When urinary PO2 fell to ≤15 mmHg, for more than or equal to the median duration for all patients (4.8 min/h surgery), the odds of AKI were 4.85 (95% CI 1.64-14.40), P = 0.004. The area under the receiver-operator curve for this parameter alone was 0.69, and was 0.89 when other variables with P ≤ 0.10 in univariable analysis were included in the model. Conclusion: Low urinary PO2 during adult cardiac surgery requiring CPB predicts AKI, so may identify patients in which intervention to improve renal oxygenation might reduce the risk of AKI.

The prognostic value of highly sensitive cardiac troponin assays for adverse events in men and women with stable heart failure and a preserved vs. reduced ejection fraction.

AIMS: Circulating biomarkers are important in the diagnosis, risk stratification and management of patients with heart failure (HF). Given the current lack of biomarkers in HF with preserved ejection fraction (HFpEF), we aimed to investigate the prognostic performance of the newly developed high-sensitivity (hs) assays for cardiac troponin I (hsTnI) compared with troponin T (hsTnT) for adverse events in HFpEF vs. HF with reduced ejection fraction (HFrEF). Findings in these two HF subgroups were also compared with those in the recently defined HF with mid-range ejection fraction (HFmrEF) subgroup. METHODS AND RESULTS: Both hsTnI and hsTnT were measured in 1096 patients with HFrEF [left ventricular ejection fraction (LVEF) <50%; n = 853] or HFpEF (LVEF ≥50%; n = 243) enrolled in the Singapore Heart Failure Outcomes and Phenotypes (SHOP) study. Both troponin assays were more strongly associated with the composite endpoint (all-cause mortality or first rehospitalization for HF) in HFpEF than in HFrEF. The hsTnT assay provided the greatest additional prognostic value in HFpEF in comparison with hsTnI and NT-proBNP. TnI was more strongly associated with composite events in men with HFpEF [hazard ratio (HR) 3.33, 95% confidence interval (CI) 1.82-6.09; P < 0.001 per standard deviation (SD) increase in log-transformed hsTnI] than in women with HFpEF (HR 1.35, 95% CI 0.94-1.93; P = 0.10 per SD increase in log-transformed hsTnI). CONCLUSIONS: There is a potential role for the prognostic use of high-sensitivity troponin assays, particularly hsTnT, in men and women with HFpEF. The predictive association of hsTnI with outcome appears strongest in men with HFpEF.

Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients With Heart Failure.

OBJECTIVES: The study sought to compare the prevalence, clinical correlates and prognostic impact of diabetes in Southeast Asian versus white patients with heart failure (HF) with preserved or reduced ejection fraction. BACKGROUND: Diabetes mellitus is common in HF and is associated with impaired prognosis. Asia is home to the majority of the world's diabetic population, yet data on the prevalence and clinical significance of diabetes in Asian patients with HF are sparse, and no studies have directly compared Asian and white patients. METHODS: Two contemporary population-based HF cohorts were combined: from Singapore (n = 1,002, median [25th to 75th percentile] age 62 [54 to 70] years, 76% men, 19.5% obesity) and Sweden (n = 19,537, 77 [68 to 84] years, 60% men, 24.8% obesity). The modifying effect of ethnicity on the relationship between diabetes and clinical correlates or prognosis (HF hospitalization and all-cause mortality) was examined using interaction terms. RESULTS: Diabetes was present in 569 (57%) Asian patients versus 4,680 (24%) white patients (p < 0.001). Adjusting for clinical covariates, obesity was more strongly associated with diabetes in white patients (odds ratio [OR]: 3.45; 95% confidence interval [CI]: 2.86 to 4.17) than in Asian patients (OR: 1.82; 95% CI: 1.13 to 2.96; pinteraction = 0.026). Diabetes was more strongly associated with increased HF hospitalization and all-cause mortality in Asian patients (hazard ratio: 1.50; 95% CI: 1.21 to 1.87) than in white patients (hazard ratio: 1.29; 95% CI: 1.22 to 1.36; pinteraction = 0.045). CONCLUSIONS: Diabetes was 3-fold more common in Southeast Asian compared to white patients with HF, despite younger age and less obesity, and more strongly associated with poor outcomes in Asian patients than white patients. These results underscore the importance of ethnicity-tailored aggressive strategies to prevent diabetes and its complications.

Molecular basis of familial hypercholesterolemia.

PURPOSE OF REVIEW: To provide an overview about the molecular basis of familial hypercholesterolemia. RECENT FINDINGS: Familial hypercholesterolemia is a common hereditary cause of premature coronary heart disease. It has been estimated that 1 in every 250 individuals has heterozygous familial hypercholesterolemia and that fewer than 1% of patients with familial hypercholesterolemia have been identified across the globe. If heterozygous familial hypercholesterolemia is left untreated, it is likely that coronary heart disease will manifest clinically prior to the age of 55 years and that half of all patients will prematurely die from the consequences of myocardial infarction. It is crucial to understand the molecular basis of familial hypercholesterolemia to diagnose familial hypercholesterolemia properly. SUMMARY: The phenotype of familial hypercholesterolemia is caused by more than 1700 mutations the LDLR, apoB and PCSK9 genes, which explains approximately 85% of familial hypercholesterolemia cases. By means of next-generation sequencing, an increasing number of mutations in established and putative novel genes associated with this phenotype have been identified.

Ethnic differences in the association of QRS duration with ejection fraction and outcome in heart failure.

BACKGROUND: QRS duration (QRSd) criteria for device therapy in heart failure (HF) were derived from predominantly white populations and ethnic differences are poorly understood. METHODS: We compared the association of QRSd with ejection fraction (EF) and outcomes between 839 Singaporean Asian and 11 221 Swedish white patients with HF having preserved EF (HFPEF)and HF having reduced EF (HFREF) were followed in prospective population-based HF studies. RESULTS: Compared with whites, Asian patients with HF were younger (62 vs 74 years, p<0.001), had smaller body size (height 163 vs 171 cm, weight 70 vs 80 kg, both p<0.001) and had more severely impaired EF (EF was <30% in 47% of Asians vs 28% of whites). Overall, unadjusted QRSd was shorter in Asians than whites (101 vs 104 ms, p<0.001). Lower EF was associated with longer QRSd (p<0.001), with a steeper association among Asians than whites (pinteraction<0.001), independent of age, sex and clinical covariates (including body size). Excluding patients with left bundle branch block (LBBB) and adjusting for clinical covariates, QRSd was similar in Asians and whites with HFPEF, but longer in Asians compared with whites with HFREF (p=0.001). Longer QRSd was associated with increased risk of HF hospitalisation or death (absolute 2-year event rate for ≤120 ms was 40% and for >120 ms it was 52%; HR for 10 ms increase of QRSd was 1.04 (1.03 to 1.06), p<0.001), with no interaction by ethnicity. CONCLUSION: We found ethnic differences in the association between EF and QRSd among patients with HF. QRS prolongation was similarly associated with increased risk, but the implications for ethnicity-specific QRSd cut-offs in clinical decision-making require further study.

Enantio- and diastereoselective synthesis of γ-amino alcohols.

The γ-amino alcohol structural motif is often encountered in drugs and natural products. We developed two complementary catalytic diastereoselective methods for the synthesis of N-PMP-protected γ-amino alcohols from the corresponding ketones. The anti-products were obtained through Ir-catalyzed asymmetric transfer hydrogenation, the syn-products via Rh-catalyzed asymmetric hydrogenation.

Clinical Features of Lysosomal Acid Lipase Deficiency.

OBJECTIVE: The aim of this study was to characterize key clinical manifestations of lysosomal acid lipase deficiency (LAL D) in children and adults. METHODS: Investigators reviewed medical records of LAL D patients ages ≥5 years, extracted historical data, and obtained prospective laboratory and imaging data on living patients to develop a longitudinal dataset. RESULTS: A total of 49 patients were enrolled; 48 had confirmed LAL D. Mean age at first disease-related abnormality was 9.0 years (range 0-42); mean age at diagnosis was 15.2 years (range 1-46). Twenty-nine (60%) were male patients, and 27 (56%) were <20 years of age at the time of consent/assent. Serum transaminases were elevated in most patients with 458 of 499 (92%) of alanine aminotransferase values and 265 of 448 (59%) of aspartate aminotransferase values above the upper limit of normal. Most patients had elevated low-density lipoprotein (64% patients) and total cholesterol (63%) at baseline despite most being on lipid-lowering therapies, and 44% had high-density lipoprotein levels below the lower limit of normal. More than half of the patients with liver biopsies (n = 31, mean age 13 years) had documented evidence of steatosis (87%) and/or fibrosis (52%). Imaging assessments revealed that the median liver volume was ∼1.15 multiples of normal (MN) and median spleen volume was ∼2.2 MN. Six (13%) patients had undergone a liver transplant (ages 9-43.5 years). CONCLUSION: This study provides the largest longitudinal case review of patients with LAL D and confirms that LAL D is predominantly a pediatric disease causing early and progressive hepatic dysfunction associated with dyslipidemia that often leads to liver failure and transplantation.

Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study.

BACKGROUND: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare. A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence implicating enhanced serotonergic neurotransmission in CFS. Genetic studies and imaging studies support the hypothesis of upregulated serotonin system in CFS. In line with the hypothesis of an increased serotonergic state in CFS, we performed a randomised clinical trial investigated the effect of 5-HT3 receptor antagonism in CFS. No benefit was found of the 5-HT3 receptor antagonist ondansetron compared to placebo.To further investigate the involvement of serotonin in CFS we performed a placebo controlled cross over pilot study investigating the effect of Acute Tryptophan Depletion. FINDINGS: Five female CFS-patients who met the US Center for Disease Control and Prevention criteria for CFS were recruited. There were two test days, one week apart. Each participant received placebo and ATD. To evaluate the efficacy of the ATD procedure tryptophan and the large neutral amino acids were measured. The outcome measures were fatigue severity, concentration and mood states. ATD resulted in a significant plasma tryptophan to large neutral amino acid ratio reduction of 96%. There were no significant differences in fatigue-, depression and concentration between the placebo- and ATD condition. CONCLUSIONS: These first five CFS-patients did not respond to the ATD procedure. However, a much larger sample size is needed to draw final conclusions on the hypothesis of an increased serotonergic state in the pathophysiology of CFS. TRIAL REGISTRATION: ISRCTN07518149.

Determination of a perfusion threshold in experimental perforator flap surgery using indocyanine green angiography.

Indocyanine green (ICG) angiography has been used in the evaluation of flap perfusion but the viability threshold has not been elucidated. In this study, we determined the threshold by comparing perfusion, using ICG imaging (SPY imaging system, LifeCell Corporation), to clinical evidence of nonviability in rat abdominal perforator flaps. Abdominal flaps, based on a single perforator, were elevated and re-inset in Sprague-Dawley rats. ICG imaging and clinical assessments were conducted preoperatively, as well as 0, 24, and 48 hours postoperatively. SPY-Q software allowed standardization of the perforator's perfusion for comparison purposes. A total of 278 random percentage measurements were made from postoperative day 0 giving a mean (SE) percentage perfusion of 26.8% (1.6%) and 59.1% (1.3%), respectively, for necrosis and survival (P<0.05). We demonstrate that ICG angiography can be readily analyzed in a perforator flap environment allowing a determination of the perfusion threshold.