Liver collagen proportionate area predicts decompensation in patients with recurrent hepatitis C virus cirrhosis after liver transplantation

Background and Aims: Current histological scoring systems do not subclassify cirrhosis. Computer‐assisted digital image analysis (DIA) of Sirius Red‐stained sections measures fibrosis morphologically producing a fibrosis ratio (collagen proportionate area [CPA]). CPA could have prognostic value within a disease stage, such as cirrhosis. The aim of the present study was to evaluate CPA in patients with recurrent hepatitis C virus (HCV) allograft cirrhosis and assess its relationship with hepatic venous pressure gradient (HVPG). Methods: In 121 consecutively‐transplanted HCV patients with HVPG, measured contemporaneously with transjugular liver biopsies, 65 had Ishak stage 5 or 6 disease (43 with HVPG measurement). Biopsies were stained with Sirius Red for DIA, and the collagen content was expressed as a CPA. In three cases, a tissue for Sirius Red staining was not obtained, and the patients were excluded. Results: Sixty‐two patients were analyzed. The median HVPG was 8 mmHg (interquartile range [IQR]: 5–10). Portal hypertension (HVPG ≥ 6 < 10 mmHg) was present in 30 (69.8%), and HVPG ≥ 10 mmHg in 13 (30.2%). The median CPA was 16% (IQR 10.75–23.25). Median Child–Pugh score and HVPG were not significantly different between Ishak fibrosis stage 5 or 6, whereas CPA was statistically different: 13% in stage 5 (IQR 8.3–12.4) versus 23% in stage 6 (IQR 17–33.7, P < 0.001). In the multivariate analysis, CPA was the only variable significantly associated with clinically‐significant portal hypertension (HVPG ≥ 10 mmHg, odds ratio: 1.085, confidence interval: 1.004–1.172, P = 0.040). A CPA of 14% was the best cut‐off value for clinically‐significant portal hypertension (CSPH) and liver decompensation, which occurred in 24 patients. Event‐free survival was significantly shorter in patients with CSPH or with a CPA value ≥ 14%, or with a combination of both. Conclusion: In Ishak stages 5 and 6, CPA correlated with HVPG, but had a wider range of values, suggesting a greater sensitivity for distinguishing “early” from “late” severe fibrosis/cirrhosis. CPA was a unique, independent predictor of HVPG ≥ 10 mmHg. CPA can be used to subclassify cirrhosis and for prognostic stratification.     

Impact of reduced levels of protein C, free protein S and antithrombin in normal frozen plasma on the interpretation of patients' results

The objective of this study was to investigate the effect of freezing of normal plasma samples on protein C, free protein S (FPS) and antithrombin levels in order to determine its potential impact on the interpretation of the results of similarly frozen patients' samples. Protein C, FPS and antithrombin levels were measured by clotting-based test, by sandwich ELISA and by chromogenic assay, respectively, in 50 normal plasma samples prior to freezing, and after 2 and 4 weeks in parallel aliquots frozen at -25°C. The mean levels of the three proteins dropped significantly after a fortnight's freezing, protein C: 130.7-122.8% (P < 0.0246); FPS: 105.9-94.1% (P < 0.0016); antithrombin: 103.2-95.8% (P < 0.0001). The corresponding inter-assay coefficient of variances of the two sets of results were 8.9, 6.6 and 9.3%. Thereafter, only FPS declined significantly (84.3%) (P < 0.0001). In two of 48 and five of 48 cases at the end of 2 and 4 weeks, respectively, the levels of FPS values went below the lower limit of the normal range established from the 50 plasma samples. Freezing of plasma at -25°C for 24 h per se did not alter the levels of protein C and antithrombin and caused only a negligible change in FPS levels. Since 6, 4 and 14% of normal plasma samples would have been labeled as antithrombin, protein C and protein S deficient, respectively, had the tests been performed after 4 weeks of freezing, it is recommended that for correct interpretation of the results, laboratories should establish their reference ranges on normal samples frozen for the same period of time as the patients' samples.     

Acute hypoxemia in a parturient with primary ciliary dyskinesia following the administration of intravenous oxytocin: a case report

Purpose

We present the case of a parturient diagnosed with primary ciliary dyskinesia with secondary bronchiectasis who developed significant hypoxemia following administration of intravenous oxytocin during Cesarean delivery under spinal anesthesia. This case suggests that oxytocin can affect pulmonary vascular tone and interfere with the protective effects of hypoxic vasoconstriction.

Clinical features

A 35-yr-old primigravida at 37 weeks gestation presented for a scheduled Cesarean delivery due to breech positioning and fetal abnormalities. The patient had a diagnosis of primary ciliary dyskinesia and had undergone a right middle lobectomy seven years earlier for resultant bronchiectasis. Pulmonary function testing in the month prior to delivery showed a 4% decline in her baseline FEV₁ to 1.06 L (32% of predicted value) but she was functionally well. The patient initially had an uneventful spinal anesthetic and maintained an oxygen saturation of 97% on room air in the supine position until delivery of her baby. An intravenous infusion of oxytocin for uterine contraction was started following removal of the placenta. The patient then became acutely hypoxemic with a drop in room air saturation to 84% but with no other accompanying hemodynamic instability. Maternal oxygen saturation did not improve with the addition of supplemental oxygen, and the patient had a significant arterial-alveolar oxygen gradient suggesting an intrapulmonary shunt. No supporting clinical, radiologic, or laboratory evidence of a thrombotic, air, or amniotic fluid embolism or mucous plug was detected. The patient remained hypoxemic during the postoperative period with gradual improvement back to baseline saturation in approximately 48 hr.

Conclusion

The vasodilatory effects of intravenous oxytocin on the pulmonary vasculature may worsen shunting and interfere with hypoxic pulmonary vasoconstriction, producing clinically significant hypoxemia in patients with comorbid lung disease. Oxytocin should be used with caution in patients with compromised lung function.     

Safety and Efficacy of Non-Cemented Femoral Fixation in Patients 75 Years of Age and Older

The aim of this study was to assess peri-operative complications, safety and efficacy of non-cemented femoral fixation in total hip arthroplasty (THA) as compared to cemented femoral fixation in the elderly population. Fifty-two matched pair analysis of patients with 75 years of age and older (104 patients), who underwent primary THA from June 1997 to December 2004, was performed based on age, sex, BMI, and Charnley classification. Mean age was 81 years (75–101) and the average follow up was 3.1 ± 2.9 years (1.2–6.4). There was no difference in peri-operative cardiopulmonary complications, pulmonary failures, deep venous thrombosis, pulmonary embolus, length of stay, or discharge deposition between the two groups. Non-cemented fixation is safe and effective in patients older than 75 years of age.     

Extracorporeal membrane oxygenation in burn and smoke inhalation injury

A systematic review and meta-analysis was conducted to assess the level of evidence for the use of extracorporeal membrane oxygenation (ECMO) in hypoxemic respiratory failure resulting from burn and smoke inhalation injury. We searched any article published before March 01, 2012. Available studies published in any language were included. Five authors rated each article and assessed the methodological quality of studies using the recommendation of the Oxford Centre for Evidence Based Medicine (OCEBM). Our search yielded 66 total citations but only 29 met the inclusion criteria of burn and/or smoke inhalation injury. There are no available systematic reviews/meta-analyses published that met our inclusion criteria. Only a small number of clinical trials, all with a limited number of patients, were available. The overall data suggests that there is no improvement in survival for burn patients suffering acute hypoxemic respiratory failure, with the use of ECMO. ECMO run times of less than 200 h correlate with higher survival compared to 200 h or more. Scald burns show a tendency of higher survival than flame burns.     

Can Bronchoscopic Airway Anatomy Be an Indicator of Autism?

Bronchoscopic evaluations revealed that some children have double branching of bronchi (designated “doublets”) in the lower lungs airways, rather than normal, single branching. Retrospective analyses revealed only one commonality in them: all subjects with doublets also had autism or autism spectrum disorder (ASD). That is, 49 subjects exhibited the presence of initial normal anatomy in upper airway followed by doublets in the lower airway. In contrast, the normal branching pattern was noted in all the remaining 410 subjects who did not have a diagnosis of autism/ASD. We propose that the presence of doublets might be an objective, reliable, and valid biologic marker of autism/ASD.     

Parkin-Knockout Mice did not Display Increased Vulnerability to Intranasal Administration of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

The loss of nigral dopaminergic neurons in Parkinson’s disease (PD) is believed to result from interactions between genetic susceptibility and environmental factors. Although loss-of-function mutations in the parkin gene cause early-onset familial PD, the hybrid 129Sv-C57BL/6 parkin-deficient mice did not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to neurotoxicity induced by 6-hydroxydopamine (6-OHDA) or intraperitoneal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. We aimed to re-evaluate the role of parkin in a pure C57BL/6 background after an acute intranasal (i.n.) MPTP administration, a new route of toxin delivery to the brain that mimics environmental exposure to neurotoxins. We found that the deficiency of parkin gene modifies the d-amphetamine-induced locomotion in saline-treated animals. Intranasal MPTP induced Parkinsonism in parkin^+/+ mice, through depletion of striatal dopamine, decreased number of dopaminergic neurons in the substantia nigra, and decreased d-amphetamine-induced hyperlocomotion. Additionally, the deletion of the parkin gene in a pure C57BL/6 background did not lead to increased vulnerability to i.n. MPTP-induced neurotoxicity. Moreover, the i.n. MPTP induced nigral astrogliosis predominantly in the pars reticulata in wild type and parkin^?/? mice. Taken together, these results showed that the absence of parkin did not modify the vulnerability of nigrostriatal dopaminergic pathway after i.n. MPTP intoxication, suggesting that independently of mouse strain, the endogenous parkin is not required for protection of this system. These findings also suggest that the development of familial parkin-linked PD is not associated with exposure to environmental factors that specifically affects the dopaminergic system.     

Morphology and performance relationship studies on biodegradable ternary blends of poly(3-hydroxybutyrate-co-3-hydroxyvalerate), polylactic acid,and polypropylene carbonate

A biodegradable ternary blend fabricated from polylactic acid (PLA), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and polypropylene carbonate (PPC) with a good balance of stiffness and toughness via optimizing the composition ratio and morphological structure is, to the best of the authors'' knowledge, reported here for the first time. The optimal blend formulation is comprised of 20% PLA, 40% PHBV, and 40% PPC, which possesses a tensile strength measuring 44 MPa and an elongation at break measuring at 215%. Thermal performance analysis revealed an HDT value of 72 °C. The Harkins equation predicts that the three immiscible polymers formed a complete wetting morphology, which was confirmed by scanning electrical microscopy. As the PPC content of the ternary blends is increased, the material undergoes morphological transition from droplet to co-continuous structure, resulting in significant improvement of elongation at break (approximately 40 times higher than that of the PLA–PHBV binary blend). Excellent stiffness and over 200% elongation at break make these sustainable ternary blends feasible for use in packaging as substitutes for certain non-biodegradable petroleum-based single use plastics.

Morphological arrangement leads to biodegradable stiffness–toughness–HDT balanced ternary blends.