Outcomes for haematological cancer patients admitted to an intensive care unit in a university hospital

Background

Haematological cancer (HC) patients are increasingly requiring intensive care (ICUs). The aim of this study was to investigate the outcome of HC patients in our ICU and evaluate 5 days-full support as a breakpoint for patients’ re-assessment for support.

Persistent polyamorphism in the chiton tooth: From a new biomineral to inks for additive manufacturing

Engineering structures that bridge between elements with disparate mechanical properties are a significant challenge. Organisms reap synergy by creating complex shapes that are intricately graded. For instance, the wear-resistant cusp of the chiton radula tooth works in concert with progressively softer microarchitectural units as the mollusk grazes on and erodes rock. Herein, we focus on the stylus that connects the ultrahard and stiff tooth head to the flexible radula membrane. Using techniques that are especially suited to probe the rich chemistry of iron at high spatial resolution, in particular synchrotron Mössbauer and X-ray absorption spectroscopy, we find that the upper stylus of Cryptochiton stelleri is in fact a mineralized tissue. Remarkably, the inorganic phase is nano disperse santabarbaraite, an amorphous ferric hydroxyphosphate that has not been observed as a biomineral. The presence of two persistent polyamorphic phases, amorphous ferric phosphate and santabarbaraite, in close proximity, is a unique aspect that demonstrates the level of control over phase transformations in C. stelleri dentition. The stylus is a highly graded material in that its mineral content and mechanical properties vary by a factor of 3 to 8 over distances of a few hundred micrometers, seamlessly bridging between the soft radula and the hard tooth head. The use of amorphous phases that are low in iron and high in water content may be key to increasing the specific strength of the stylus. Finally, we show that we can distill these insights into design criteria for inks for additive manufacturing of highly tunable chitosan-based composites.

Biominerals are broadly used by organisms to reinforce structural materials, enabling for instance locomotion, feeding, and defense but also finding application in sensing (1). A defining principle of mineralized tissues is their composite nature, reaping synergy from the combination of a soft macromolecular matrix and a hard, inorganic mineral phase (2, 3). Organisms functionally grade such composites by precisely controlling the phase, size, shape, orientation, dispersion, and spatial distribution of mineral nanoparticles. Harnessing the biological capability to create composites that combine complex shape with mechanical properties that are graded intricately yet over several orders of magnitude in range is of interest for a broad range of functional materials—for instance, for soft robotics (4).Chitons, a class of marine mollusks, are best known for the extreme hardness, rich chemistry, and intricate phase assemblage of their radula teeth (Fig. 1 and SI Appendix, Fig. S1, for recent reviews see refs. 5 and 6; for a cross-cutting review that includes chiton biominerals, see ref. 7). However, the mechanical system of their dentition is not only significantly more complex but also based on a continuous organic phase that is differentially reinforced. The chiton therefore serves as an excellent model system to study biological mechanisms and design principles.Open in a separate windowFig. 1.Radula teeth of C. stelleri. (A) Ventral aspect of C. stelleri [Image credit: Linda Schroeder (photographer)]. (B) Mouth and protruding anterior end of radula (ra) (8). Image credit: VicHigh Marine/David Young. (C) Mosaic image of the entire radula showing all stages of development, including deposition of the organic scaffold (stage I), infiltration of the cusp with ferrihydrite (stage II), conversion to magnetite (stage III), mineralization of the core (stage IV), and mature teeth (stage V). (D) SEM image of the anterior end of the radula with mature teeth. Major lateral teeth consist of the tricuspidate head (hd, 400 × 350 × 150 µm³) and the stylus (st, L-shape 1,400 × 1,400 × 350 µm³). The stylus anchors teeth on the thin (∼100 µm; SI Appendix, Fig. S10C) and flexible radula membrane (rm). The stylus canal (stc) runs along the length of the stylus but terminates below the head. (E) Rendering of a virtual section of a tooth head (hd) and upper stylus (st) generated from a 3D reconstruction of the normalized linear attenuation coefficient (LAC) as determined by synchrotron microcomputed tomography. Note the LAC is highest for the outer magnetite layer (ml) of the head, intermediate for AFP-based composite of the core (co), and rather low in the stylus. Typical for Cryptochiton type teeth, the core is exposed in a window (wi) in the magnetite layer on the trailing (anterior) face of the tooth.The chiton radula is slender ribbon with transverse rows of teeth (Fig. 1 B–D) (9). Two outsize major lateral teeth make contact with the substrate during grazing. Major lateral teeth consist of a tooth head and stylus (Fig. 1 D and E and SI Appendix, Figs. S1 and S10) that is anchored on the radula membrane (10, 11). The stylus canal runs along the length of the hollow stylus and terminates in a dead end below the junction zone between stylus and cusp. During the feeding stroke, the radula slides over a curved supporting surface and bends in two orthogonal directions. This results in a characteristic scraping and sweeping motion of radula teeth (12). The loss of entire rows of teeth due to wear is compensated for by synthesis of new teeth at the posterior end (13, 14). Newly formed teeth mature in several stages as they are transported toward the anterior end by the radula membrane (15). As a result, their entire development can be observed in one animal (Fig. 1C).The function of the radula requires highly disparate material properties. The tooth complex is based on a continuous organic scaffold comprised of semicrystalline, partially deacetylated α-chitin and protein and may be crosslinked by tanning reactions (16). The tooth head is comprised of a highly mineralized cusp with exceptional hardness, wear resistance, and self-sharpening properties (17). The cusp is supported by a softer core. In Cryptochiton-type teeth, magnetite covers the entire posterior surface (leading edge) of the cusp and all but a rectangular window on the anterior surface (trailing edge) (5). The biomineral of the tooth core, amorphous ferric phosphate (AFP), is thus exposed in the window (Fig. 1E and SI Appendix, Fig. S1) (18). Use of at least two biominerals is typical for chiton teeth, and a considerable number has been identified in the core of different species (see ref. 5 and references therein). Additionally, ferrihydrite occurs as a transient precursor phase in stage II of radula development (Fig. 1C) (18).The entire head is mounted on the stylus, an L-shaped chitinous tissue that is integral to the complex movement of the tooth head during the feeding stroke (Fig. 1D and SI Appendix, Fig. S10 A and B) (19). The stylus connects the tooth head to the radula and orients the tooth with respect to the substratum (20). The radula membrane (Fig. 1D and SI Appendix, Fig. S10C) has lower stiffness to accommodate complex shape changes but at the same time must be strong, tough, and resistant to fatigue to survive the cycling bending and unbending during feeding. As a consequence of these vastly different requirements, we expect that mechanical properties are strongly graded. This is well documented for the cusp and core of radula teeth but less explored for the stylus and radula (17, 21, 22).The stylus and the radula membrane are generally referred to as unmineralized tissues, even though the presence of transient mineral has been suggested and the junction zone does mineralize in later stages (5, 22). However, the chemical form in which iron appears in the junction zone and stylus remains unclear. We therefore set out to map the redox state and chemical environment of iron in the tooth of Cryptochiton stelleri with the long-term goal to trace these parameters over the development of the radula and thus gain insight into the mechanisms at play. This would then provide a foothold on the way to designing bio-inspired syntheses.Given the complex shape (Fig. 1 D and E) and small size of chiton teeth and the extraordinarily rich chemistry of iron, mapping of multiple, often poorly crystalline phases requires techniques that combine high spatial resolution with sensitivity for subtle differences in oxidation state and coordination geometry of iron. Synchrotron Mössbauer spectroscopy (SMS) recently emerged as a powerful tool that combines high spatial resolution with the deep chemical insights offered by classical Mössbauer spectroscopy (23–25). Herein, we report on our discovery of a biomineral in the mature upper stylus of C. stelleri using SMS and correlative imaging and spectroscopy techniques.     

An unusual case of osteoid osteoma clinically mimicking sacroiliitis

Osteoid osteoma is one of the unusual causes of musculosceletal pain. A case of a 21-year-old man who had low back and hip pain radiating to the posterior thigh for 3 years is presented. Pain was worse at night but reduced with the use of nonsteroidal anti-inflammatory drugs. Straight leg raising test was negative. Patrick–Fabere and sacroiliac compression tests were positive on the right. Neurological examination was normal. Lumbar spinal and pelvic radiographs were normal except for sclerosis at the inferior half of the iliac bone adjacent to the right sacroiliac joint. Sedimentation rate, C-reactive protein, and whole blood counts were normal. Bone scan showed nonspecific increased uptake. Computed tomography revealed the presence of diffuse sclerosis at inferior half of the right iliac bone extending to medial border of sacroiliac joint with subcortical osteolytic region and centrally hyperdense sclerotic nidus inside.     

Clinical presentations of chlamydial and non-chlamydial reactive arthritis

The aim of this study was to investigate the triggering micro-organisms and the clinical as well as laboratory differences between Chlamydial and non-chlamydial reactive arthritis (ReA) in a prospective study on 98 patients with acute/subacute arthritis. An inciting organism was found in 42 patients. Eighteen of these were chlamydial. Fifty-seven percent of all ReA patients were carriers for HLA-B27, which increased to 67% in the chlamydial group. Chlamydial ReA patients had more urethritis (P<0.05) with a longer period between arthritis and inciting infection, significantly lower CRP levels, and involved joint counts (P<0.05). Additionally, sacroiliitis was more frequent besides extra-articular manifestations in chlamydial ReA group. This study shows that chlamydial ReA differs in some points from non-chlamydial ReA, which in turn may affect the evaluation of an arthritic patient. ReA due to chlamydia more frequently encompasses a monoarticular or oligoarticular clinical picture with predominant distal extremity involvement. Non-chlamydial ReA presents higher joint counts and may involve upper extremity joints.     

An awl inflicted chest wound causing acute myocardial infarction

Penetrating chest wounds are frequent. When involving the heart, they usually cause tamponade. In our case, caused by an awl, laceration of the LAD occured without intrapericardial bleeding. The coronary angiography demonstrates the damage to the wall of the LAD.     

TRAIL-R2 promotes skeletal metastasis in a breast cancer xenograft mouse model

Despite improvements in detection, surgical approaches and systemic therapies, breast cancer remains typically incurable once distant metastases occur. High expression of TRAIL-R2 was found to be associated with poor prognostic parameters in breast cancer patients, suggesting an oncogenic function of this receptor. In the present study, we aimed to determine the impact of TRAIL-R2 on breast cancer metastasis. Using an osteotropic variant of MDA-MB-231 breast cancer cells, we examine the effects of TRAIL-R2 knockdown in vitro and in vivo. Strikingly, in addition to the reduced levels of the proliferation-promoting factor HMGA2 and corresponding inhibition of cell proliferation, knockdown of TRAIL-R2 increased the levels of E-Cadherin and decreased migration. In vivo, these cells were strongly impaired in their ability to form bone metastases after intracardiac injection. Evaluating possible underlying mechanisms revealed a strong downregulation of CXCR4, the receptor for the chemokine SDF-1 important for homing of cancers cells to the bone. In accordance, cell migration towards SDF-1 was significantly impaired by TRAIL-R2 knockdown. Conversely, overexpression of TRAIL-R2 upregulated CXCR4 levels and enhanced SDF-1-directed migration. We therefore postulate that inhibition of TRAIL-R2 expression could represent a promising therapeutic strategy leading to an effective impairment of breast cancer cell capability to form skeletal metastases.