Abundant deposition of bronchoalveolar fibrin and fibronectin occurs during the exudative phase of the adult respiratory distress syndrome (ARDS), promoting hyaline-membrane formation and subsequent alveolar fibrosis. To explore the mechanisms that account for the persistence of bronchoalveolar fibrin and fibronectin, we compared the activity of urokinase, which is necessary for plasminogen activation and fibrin degradation, in cell-free bronchoalveolar-lavage fluid from 8 patients with ARDS, 9 patients with acute pulmonary diseases other than ARDS, and 10 normal subjects. The mean level of urokinase activity in the lavage fluid from the patients with ARDS was 0.003 IU per milliliter of fluid (range, 0 to 0.008), which was significantly lower (P = 0.001) than the level in the fluid from either the patients with pulmonary diseases other than ARDS (0.118 IU per milliliter [range, 0.032 to 0.295]) or the normal subjects (0.129 IU per milliliter [range, 0.045 to 0.198]). The lavage fluid from all the patients with ARDS also had antiplasmin activity, which would promote the persistence of fibrin. A true decrease in urokinase activity was confirmed by the failure of the lavage fluid from the patients with ARDS to convert [125I]plasminogen to plasmin. Despite the low urokinase activity, immunochemical assays revealed normal levels of urokinase antigen in the fluid from the patients with ARDS, suggesting the presence of urokinase inhibitors. Inhibitors were demonstrated directly by a fibrin gel-underlay assay that detects complexes of urokinase with inhibitors. Plasminogen-activator inhibitor type 1 was the principal inhibitor identified. We conclude that increased antifibrinolytic activity due to both urokinase inhibitors and antiplasmins in the bronchoalveolar compartment of patients with ARDS contributes to the formation and persistence of hyaline membranes, a key component of alveolar histopathology in ARDS.

Traditional kidney biomarkers are insensitive indicators of acute kidney injury, with meaningful changes occurring late in the course of injury. The aim of this work was to demonstrate the diagnostic potential of urinary osteopontin (OPN) and neutrophil gelatinase-associated lipocalin (NGAL) for drug-induced kidney injury (DIKI) in rats using data from a recent regulatory qualification submission of translational DIKI biomarkers and to compare performance of NGAL and OPN to five previously qualified DIKI urinary biomarkers. Data were compiled from 15 studies of 11 different pharmaceuticals contributed by Critical Path Institute's Predictive Safety Testing Consortium (PSTC) Nephrotoxicity Working Group (NWG). Rats were given doses known to cause DIKI or other target organ toxicity, and urinary levels of the candidate biomarkers were assessed relative to kidney histopathology and serum creatinine (sCr) and blood urea nitrogen (BUN).OPN and NGAL outperformed sCr and BUN in identifying DIKI manifested as renal tubular epithelial degeneration or necrosis. In addition, urinary OPN and NGAL, when used with sCr and BUN, increased the ability to detect renal tubular epithelial degeneration or necrosis. NGAL and OPN had comparable or improved performance relative to Kim-1, clusterin, albumin, total protein, and beta-2 microglobulin. Given these data, both urinary OPN and NGAL are appropriate for use with current methods for assessing nephrotoxicity to identify and monitor DIKI in regulatory toxicology studies in rats. These data also support exploratory use of urinary OPN and NGAL in safety monitoring strategies of early clinical trials to aid in the assurance of patient safety.

Intravascular large B-cell lymphoma, also known as angiotrophic large cell lymphoma, is a rare disorder where neoplastic lymphoid cells proliferate within the walls of small- to medium-sized blood vessels. Peripheral neuropathy and other neurological manifestations, including stroke and dementia, are common, but cases of isolated multiple mononeuropathies in the absence of systemic symptoms are distinctly rare. We present an unusual case of biopsy-proved angiotrophic large cell lymphoma presenting exclusively with multiple mononeuropathies.

Introduction: This matched cohort study aims to determine whether the presence of a spinal arthrodesis (SA) compromises outcome of total hip arthroplasty (THA) and whether the outcome is better if THA is performed before- (THA-1st) or after- SA (THA-2nd). Methods: This is a single centre, multi-surgeon, review of prospective data. Thirty-seven patients (47 hips) that had SA and 1° THA(s), formed the cases (26 THA-1st; 21 THA-2nd). Most cases had 1-level SA ( n = 24). Controls were patients without SA that had THA, over the same period matched for age, gender and prosthesis type. Outcome measures included complication-, revision- rates, Oxford-Hip- and Harris-Hip-Scores (OHS/HHS) (Δ: difference between pre- and post-operative scores). This is a single-centre, multi-surgeon, review of prospective data. Results: At a mean follow-up of 6 years, more complications were seen in cases of THA and SA compared with controls without SA (7 vs. 2) ( p = 0.03). Consequently, more cases were revised ( n = 4) compared with controls ( n = 0) ( p = 0.02). There were no differences in functional outcome between cases and controls ( p = 0.1–0.6). No differences in complications- (4/26 vs. 3/21; p = 1.00) or revision- rates (2/26 vs. 2/21; p = 1.00) were seen between THA-1st and THA-2nd Groups. The THA-1st Group had higher pre- and post-operative OHS/HHS, compared to the THA-2nd Group. However, no significant difference in ΔOHS (24 vs. 17) and ΔHHS (39 vs. 26) were seen between the THA-1st and THA-2nd Groups ( p = 0.1). Conclusions: Patients with THA and SA, had increased rates of revision; but no differences in patient-reported outcome measures (PROMs) were detected. Addressing the hip pathology first may be associated with improved functional outcome.