Sex-specific Differences of the Infraacetabular Corridor: A Biomorphometric CT-based Analysis on a Database of 523 Pelves

BackgroundAn infraacetabular screw path facilitates the closure of a periacetabular fixation frame to increase the plate fixation strength in acetabular fractures up to 50%. Knowledge of the variance in corridor sizes and axes has substantial surgical relevance for safe screw placement.Questions/purposes(1) What proportion of healthy pelvis specimens have an infraacetabular corridor that is 5 mm or larger in diameter? (2) Does a universal corridor axis and specific screw entry point exist? (3) Are there sex-specific differences in the infraacetabular corridor size or axis and are these correlated with anthropometric parameters like age, body weight and height, or the acetabular diameter?MethodsA template pelvis with a mean shape from 523 segmented pelvis specimens was generated using a CT-based advanced image analyzing system. Each individual pelvis was registered to the template using a free-form registration algorithm. Feasible surface regions for the entry and exit points of the infraacetabular corridor were marked on the template and automatically mapped to the individual samples to perform a measurement of the maximum sizes and axes of the infraacetabular corridor on each specimen. A minimum corridor diameter of at least 5 mm was defined as a cutoff for placing a 3.5-mm cortical screw in clinical settings.ResultsIn 484 of 523 pelves (93%), an infraacetabular corridor with a diameter of at least 5 mm was found. Using the mean axis angulations (54.8° [95% confidence interval {CI}, 0.6] from anterocranial to posterocaudal in relation to the anterior pelvic plane and 1.5° [95% CI, 0.4] from anteromedial to posterolateral in relation to the sagittal midline plane), a sufficient osseous corridor was present in 64% of pelves. Allowing adjustment of the three-dimensional axis by another 5° included an additional 25% of pelves. All corridor parameters were different between females and males (corridor diameter, 6.9 [95% CI, 0.2] versus 7.7 [95% CI, 0.2] mm; p < 0.001; corridor length, 96.2 [95% CI, 0.7] versus 106.4 [95% CI, 0.6] mm; p < 0.001; anterior pelvic plane angle, 54.0° [95% CI, 0.9] versus 55.3° [95% CI, 0.8]; p < 0.01; sagittal midline plane angle, 4.3° [95% CI, 0.6] versus −0.3° [95% CI, 0.5]; p < 0.001).ConclusionThis study provided reference values for placement of a 3.5-mm cortical screw in the infraacetabular osseous corridor in 90% of female and 94% of male pelves. Based on the sex-related differences in corridor axes, the mean screw trajectory is approximately parallel to the sagittal midline plane in males but has to be tilted from medial to lateral in females. Considering the narrow corridor diameters, we suggest an individual preoperative CT scan analysis for fine adjustments in each patient.     

From the Cover: Breaking the diffraction limit of light-sheet fluorescence microscopy by RESOLFT

We present a plane-scanning RESOLFT [reversible saturable/switchable optical (fluorescence) transitions] light-sheet (LS) nanoscope, which fundamentally overcomes the diffraction barrier in the axial direction via confinement of the fluorescent molecular state to a sheet of subdiffraction thickness around the focal plane. To this end, reversibly switchable fluorophores located right above and below the focal plane are transferred to a nonfluorescent state at each scanning step. LS-RESOLFT nanoscopy offers wide-field 3D imaging of living biological specimens with low light dose and axial resolution far beyond the diffraction barrier. We demonstrate optical sections that are thinner by 5–12-fold compared with their conventional diffraction-limited LS analogs.Far-field nanoscopy (1, 2) methods discern features within subdiffraction distances by briefly forcing their molecules to two distinguishable states for the time period of detection. Typically, fluorophores are switched between a signaling “on” and a nonsignaling (i.e., dark) “off” state. Depending on the switching and fluorescence registration strategy used, these superresolution techniques can be categorized into coordinate-stochastic and coordinate-targeted approaches (2). The latter group of methods, comprising the so-called RESOLFT [reversible saturable/switchable optical (fluorescence) transitions] (1, 3–7) approaches, have been realized using patterns of switch-off light with one or more zero-intensity points or lines, to single out target point (zero-dimensional) or line (1D) coordinates in space where the fluorophores are allowed to assume the on state. The RESOLFT idea can also be implemented in the inverse mode, by using switch-on light and confining the off state. In any case, probing the presence of molecules in new sets of points or lines at every scanning step produces images.Owing to the nature of the on and off states involved––first excited electronic and ground state––stimulated emission depletion (STED) (3) and saturated structured illumination microscopy (SSIM) (8), which both qualify as variants of the RESOLFT principle, typically apply light intensities in the range of MW/cm² and above. Especially when imaging sensitive samples where photoinduced changes must be avoided, RESOLFT is preferably realized with fluorophores which lead to the same factor of resolution improvement at much lower intensities of state-switching light. Reversibly switchable fluorescent proteins (RSFPs) are highly suitable for this purpose (4–7, 9), as transitions between their metastable on and off states require 5 orders of magnitude lower threshold intensities than STED/SSIM to guarantee switch-off. Suitable spectral properties, relatively fast millisecond switching kinetics, and high photostability of recently developed yellow-green-emitting RSFPs like rsEGFP (5), rsEGFP2 (7), and rsEGFP(N205S) (10) compared with early RSFPs have indeed enabled RESOLFT nanoscopy in living cells and tissues. To date, RSFP-based RESOLFT has achieved resolution improvements by factors of 4–5 in rsEGFP2-labeled samples (7). To further reduce the imaging time, massive parallelization of scanning has been reported (10). However, the diffraction-limited axial resolution and lack of background suppression restrict applications to thin samples.Imaging applications typically require careful tuning of imaging parameters including speed, contrast, photosensitivity, and spatial resolution, depending on the information that is sought. Light-sheet fluorescence microscopy (LSFM) (11–15) stands out by its ability to balance most of these parameters for 3D imaging of living specimens. Recently reenacted as the selective plane illumination microscope (13), this microscopy mode has sparked increasing interest notably because of its short acquisition times in 3D imaging and low phototoxicity in living specimens. It excites fluorophores only in a thin diffraction-limited slice of the sample, perpendicular to the direction of fluorescence detection. The LS is generated by a cylindrical lens which focuses an expanded laser beam in only one direction onto the specimen or into the back-focal plane of an illumination objective. Alternatively, a single beam is quickly moved as a “virtual” LS (16) across a specimen section.In such conventional LSFM imaging, the lateral resolution is determined by the numerical aperture (N.A.) of the detection objective (17), whereas axial resolution is given by the LS thickness, provided the latter is thinner than the axial extent of the point-spread function describing the imaging process from the focal plane of the detecting lens to the camera. In a previous study, the axial resolution of LSFM was pushed to the diffraction limit by using the full aperture of the illumination objective with Gaussian beams; this was carried out for practically useful combinations of N.A. (e.g., 0.8 for both illumination and detection objectives) permissible in light of the geometrical constraints given by the objective lens dimensions (18). High-N.A. illumination comes with short Rayleigh ranges of Gaussian beams, which inherently limit the field of view (FOV) along the direction of illumination. Scanned Bessel beams for diffraction-limited excitation with a virtual LS (19–21) typically offer larger FOVs (22), but side lobes broaden the scanned LS in the axial direction and contribute to phototoxicity outside of the focal plane of detection (20). A more complex approach has used Bessel-beam excitation in combination with structured illumination to obtain near-isotropic (but still diffraction-limited) resolution as measured on fluorescent beads (20), albeit at the cost of acquisition time and reduced contrast due to fluorescence generated by the side lobes. In different work, axial resolution has also been improved about fourfold by acquiring two complementary orthogonal views of the sample using two alternating LSs, followed by computationally fusing image information with a deconvolution incorporating both views (23). LS approaches have also helped suppress out-of-focus background for single-molecule imaging in biological situations (e.g., in ref. 24), including at superresolution (25–27).Slight axial resolution improvement beyond the diffraction barrier has been demonstrated by overlapping a Gaussian excitation LS with a STED LS featuring a zero-intensity plane (28). Due to scattering and possibly additional aberrations caused by the wavelength difference between excitation and STED light, the maximal achievable resolution in biological specimens was severely limited. This was the case even in fixed samples. A successful application of LS-STED to living cells or organisms has not been reported. The relatively high average STED laser power required for high resolution gains calls for developing a coordinate-targeted superresolution LS approach with low-power operation, meaning a concept that does not solely rely on changing the way the light is directed to––or collected from––the sample, but a concept that harnesses an “on–off” transition for improved feature separation.     

Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!: An analysis of 116,069 THAs in the Nordic Arthroplasty Register Association (NARA) database

ResultsUnadjusted 10-year survival with the endpoint revision of any component for any reason was 92.1% (CI: 91.8–92.4). Unadjusted 10-year survival with the endpoint stem revision due to aseptic loosening varied between the stem brands investigated and ranged from 96.7% (CI: 94.4–99.0) to 99.9% (CI: 99.6–100). Of the stem brands with the best survival, stems with and without HA coating were found. The presence of HA coating was not associated with statistically significant effects on the adjusted risk of stem revision due to aseptic loosening, with an HR of 0.8 (CI: 0.5–1.3; p = 0.4). The adjusted risk of revision due to infection was similar in the groups of THAs using HA-coated and non-HA-coated stems, with an HR of 0.9 (CI: 0.8–1.1; p = 0.6) for the presence of HA coating. The commonly used Bimetric stem (n = 25,329) was available both with and without HA coating, and the adjusted risk of stem revision due to aseptic loosening was similar for the 2 variants, with an HR of 0.9 (CI: 0.5–1.4; p = 0.5) for the HA-coated Bimetric stem.InterpretationUncemented HA-coated stems had similar results to those of uncemented stems with porous coating or rough sand-blasted stems. The use of HA coating on stems available both with and without this surface treatment had no clinically relevant effect on their outcome, and we thus question whether HA coating adds any value to well-functioning stem designs.Hydroxyapatite (HA) is thought to improve early implant ingrowth and long-term stability in bone (Overgaard et al. 1997), and many stems intended for uncemented total hip arthroplasty (THA) are thus manufactured with HA coating. Several uncemented stems are only available with HA coating. Some HA-coated stems have excellent long-term outcomes in terms of the risk of revision, both for any reason and due to aseptic loosening (Capello et al. 2003, Shah et al. 2009). Registry data from Norway and Finland also indicate that certain HA-coated stems have excellent survivorship up to 10 years (Eskelinen et al. 2006, Hallan et al. 2007, Makela et al. 2008).On the other hand, a number of studies on stem survival in the setting of randomized trials or smaller observational studies have failed to show beneficial effects of HA coating on clinical outcome and implant survival when compared to alternatives such as porous coating and sand-blasted rough surfaces (McPherson et al. 1995, Tanzer et al. 2001, Kim et al. 2003, Parvizi et al. 2004, Sanchez-Sotelo et al. 2004). Meta-analyses that have pooled data from randomized or cohort studies have come to the conclusion that there is “[…] no clinically beneficial effect to the addition of HA to porous coating alone in primary uncemented hip arthroplasty” (Gandhi et al. 2009, Li et al. 2013). In addition, a Danish registry analysis found that the use of HA coating does not reduce the risk of stem revision (Paulsen et al. 2007). Furthermore, a comparison of 4,772 uncemented Bimetric stems with or without HA coating implanted between 1992 and 2009 did not reveal any difference in survival between the 2 variants (Lazarinis et al. 2011).HA was initially introduced as an implant coating to speed up and facilitate ongrowth and ingrowth of bone and thereby improve fixation, based on comprehensive preclinical and promising clinical documentation (Geesink et al. 1987, Bauer et al. 1991, Overgaard et al. 1997, Karrholm et al. 1998). Later on, concerns were raised due to findings of delamination and generation of HA particles originating from the coating with the potential to trigger osteolysis, acceleration of polyethylene wear, and subsequent implant loosening (Bloebaum and Dupont 1993, Morscher et al. 1998, Lazarinis et al. 2010). Today, there is renewed interest in HA coatings due to possible properties as a carrier for agents aimed at preventing infection (Ghani et al. 2012). Theoretical arguments for and against the use of HA coating can therefore be found. Given the renewed interest in uncemented stems—instigated by favorable outcomes after uncemented stem fixation in younger patients—the question of whether HA coating is beneficial or not is highly relevant (Eskelinen et al. 2006, Hooper et al. 2009, Swedish Hip Arthroplasty Register 2011). We therefore investigated uncemented stems with and without HA coating that are in frequent use in the Nordic countries, regarding early and long-term survival.     

Activated pancreatic stellate cells can impair pancreatic islet function in mice

Background

Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets.

Methods

Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets.

Results

PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets co-cultured with PSCs for 24–48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days.

Conclusion

Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes.     

Does tumour necrosis factor‐α inhibitor infliximab induce histological resolution of pulmonary sarcoid granulomas?

Background: Sarcoid granuloma formation involves the orchestration of cytokines and chemokines, which modulate the host's immune response to the antigen stimulus. The release of cytokines enhances expression of the pro‐inflammatory cytokine tumour necrosis factor‐α (TNF), which plays a crucial role in the formation of sarcoid granuloma, being released from T‐lymphocytes and alveolar macrophages. Objective: The aim of this study was to evaluate the effect of infliximab in a case of pulmonary sarcoidosis using a histological approach. Materials and Methods: A 44‐year‐old man with biopsy verified chronic pulmonary sarcoidosis being resistant to treatment with corticosteroids and cell cycle inhibitors. Persisting disease activity was confirmed by declining lung function tests and a positive fluorine‐18‐fluorodeoxyglucose–positron emission tomography scan. The patient was treated with a single course of infliximab 3‐mg/kg body weight; 11 days later, a single lung transplantation was performed. Immunohistological staining with the macrophage marker CD68 was performed on lung tissue and mediastinal lymph node tissue from both the initial diagnostic evaluation (prior to infliximab) as well as from the explanted lung (after infliximab). Results: Biopsy specimens from lung and mediastinal lymph nodes prior to infliximab demonstrated sarcoid granulomas, and staining with CD68 showed dense infiltration by macrophages (epithelioid cells) in the central part of the granulomas. In contrast, biopsies from the explanted lung after infliximab demonstrated acellular sarcoid granulomas with central amorphous masses, and staining with CD68 showed complete absence of macrophages. Conclusions: In this patient, the TNF inhibitor infliximab appeared to induce resolution of sarcoid granulomas starting with disappearance of macrophages probably caused by cell lysis or apoptosis. Please cite this paper as: Milman N, Andersen CB, Baslund B, Loft A and Iversen M. Does tumour necrosis factor‐α inhibitor infliximab induce histological resolution of pulmonary sarcoid granulomas? The Clinical Respiratory Journal 2007; 1:106–113.     

Terlipressin plus hydroxyethyl starch infusion: an effective treatment for hepatorenal syndrome

Ornipressin is a vasopressin analogue that can cause potent splanchnic vasoconstriction. It has been shown that, in combination with albumin infusion, ornipressin is able to reverse hepatorenal syndrome. However, its clinical use is limited by possible severe ischaemic complications. In our case, a 47-year-old man received a right hemihepatectomy for cholangiocellular carcinoma. On post-operative day three, he developed hepatorenal syndrome with ascites, peripheral oedema and oliguria (250-500 ml/day). Serum creatinine was increased to 3.5 mg/dl. The patient was treated with terlipressin, another vasopressin analogue with fewer side effects than ornipressin, (1 mg every 4 h intravenously) and hydroxyethyl starch (500 ml/day). Urine output increased to 3000 ml/day, serum creatinine decreased to normal range within 4 days and ascites and oedema disappeared. We hereby report the first case of successful treatment of hepatorenal syndrome with terlipressin and hydroxyethyl starch, which appears to be a safe and effective treatment.