Authors: Ross Davenport, Nicola Curry, Erin E Fox...

IMPORTANCE

Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage.

OBJECTIVE

To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol.

DESIGN, SETTING, AND PARTICIPANTS

CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US major trauma centers from August 2017 to November 2021. Eligible patients were injured adults requiring activation of the hospital's major hemorrhage protocol with evidence of active hemorrhage, systolic blood pressure less than 90 mm Hg at any time, and receiving at least 1 U of a blood component transfusion.

INTERVENTION

Patients were randomly assigned (in a 1:1 ratio) to receive standard care, which was the local major hemorrhage protocol (reviewed for guideline adherence), or cryoprecipitate, in which 3 pools of cryoprecipitate (6-g fibrinogen equivalent) were to be administered in addition to standard care within 90 minutes of randomization and 3 hours of injury.

MAIN OUTCOMES AND MEASURES

The primary outcome was all-cause mortality at 28 days in the intention-to-treat population.

RESULTS

Among 1604 eligible patients, 799 were randomized to the cryoprecipitate group and 805 to the standard care group. Missing primary outcome data occurred in 73 patients (principally due to withdrawal of consent) and 1531 (95%) were included in the primary analysis population. The median (IQR) age of participants was 39 (26-55) years, 1251 (79%) were men, median (IQR) Injury Severity Score was 29 (18-43), 36% had penetrating injury, and 33% had systolic blood pressure less than 90 mm Hg at hospital arrival. All-cause 28-day mortality in the intention-to-treat population was 26.1% in the standard care group vs 25.3% in the cryoprecipitate group (odds ratio, 0.96 [95% CI, 0.75-1.23]; P = .74). There was no difference in safety outcomes or incidence of thrombotic events in the standard care vs cryoprecipitate group (12.9% vs 12.7%).

CONCLUSIONS AND RELEVANCE

Among patients with trauma and bleeding who required activation of a major hemorrhage protocol, the addition of early and empirical high-dose cryoprecipitate to standard care did not improve all cause 28-day mortality.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT04704869; ISRCTN Identifier: ISRCTN14998314.

Topics: Adult; Male; Humans; Middle Aged; Female; Hemorrhage; Fibrinogen; Blood Transfusion; Blood Component Transfusion; Wounds, Penetrating

PubMed: 37824155
DOI: 10.1001/jama.2023.21019

Authors: Vidmantas Kalendra, Justinas Turčak, Gediminas Usevičius...

Following the success of cryogenic EPR signal preamplification at X-band, we present a Q-band EPR cryoprobe compatible with a standard EPR resonator. The probehead is equipped with a cryogenic ultra low-noise microwave amplifier and its protection circuit that are placed close to the sample in the same cryostat. Our cryoprobe maintains the same sample access and tuning which is typical in Q-band EPR, as well as supports high-power pulsed experiments on typical samples. The performance of our setup is benchmarked against that of existing commercial and home-built Q-band spectrometers, using CW EPR and pulsed EPR/ENDOR experiments to reveal a significant sensitivity improvement which reduces the measurement time by a factor of about 40× at 6 K temperature at reduced power levels.

PubMed: 37856964
DOI: 10.1016/j.jmr.2023.107573

Authors: Rishabh Upadhyay, Dmitry S Golubev, Yu-Cheng Chang...

The fragile nature of quantum circuits is a major bottleneck to scalable quantum applications. Operating at cryogenic temperatures, quantum circuits are highly vulnerable to amplifier backaction and external noise. Non-reciprocal microwave devices such as circulators and isolators are used for this purpose. These devices have a considerable footprint in cryostats, limiting the scalability of quantum circuits. As a proof-of-concept, here we report a compact microwave diode architecture, which exploits the non-linearity of a superconducting flux qubit. At the qubit degeneracy point we experimentally demonstrate a significant difference between the power levels transmitted in opposite directions. The observations align with the proposed theoretical model. At - 99 dBm input power, and near the qubit-resonator avoided crossing region, we report the transmission rectification ratio exceeding 90% for a 50 MHz wide frequency range from 6.81 GHz to 6.86 GHz, and over 60% for the 250 MHz range from 6.67 GHz to 6.91 GHz. The presented architecture is compact, and easily scalable towards multiple readout channels, potentially opening up diverse opportunities in quantum information, microwave read-out and optomechanics.

PubMed: 38245544
DOI: 10.1038/s41467-024-44908-w

Authors: M Marsden, J Benger, K Brohi...

Topics: Biomedical Research; Blood Coagulation Disorders; Clinical Trials as Topic; Factor VIII; Fibrinogen; Hemorrhage; Humans; United Kingdom; Wounds and Injuries

PubMed: 30686301
DOI: 10.1016/j.bja.2018.10.055

Authors: Pin-Hui Chen, Chukun Gao, Nicholas Alaniva...

We demonstrate the construction of 7 Tesla and 12 Tesla all high-temperature-superconducting (HTS) magnets, small enough to fit on your wrist. The size of the magnet reduces the cost of fabrication, decreases the fringe field to permit facile siting of magnets, and decreases the stored energy of high field magnets. These small HTS-based magnets are being developed for gyrotron microwave sources for use in high-field nuclear magnetic resonance applications. The 7 Tesla and 12 Tesla magnets employ a no-insulation winding technique and are cooled to 4.2 Kelvin in a liquid helium cryostat. The 7 Tesla magnet is a single pancake coil, made of only 9.4 m of HTS tape, with an inner diameter of 8 mm and an outer diameter of 24 mm. This magnet was charged up to 1168 Amperes, generating a field of 7.3 Tesla. The 12 Tesla magnet is comprised of two pancake coils (inner diameter of 10 mm and outer diameter of 27 mm) connected in series. This magnet reached its maximum field at a current of 850 Amperes.

PubMed: 37976810
DOI: 10.1016/j.jmr.2023.107588

Authors: S Steven Potter, Eric W Brunskill

This chapter describes detailed methods used for laser capture microdissection (LCM) of discrete subpopulations of cells. Topics covered include preparing tissue blocks, cryostat sectioning, processing slides, performing the LCM, and purification of RNA from LCM samples. Notes describe the fine points of each operation, which can often mean the difference between success and failure.

Topics: Animals; Cryoultramicrotomy; Equipment Design; Kidney; Laser Capture Microdissection; RNA

PubMed: 22639264
DOI: 10.1007/978-1-61779-851-1_19

Comparative Study

Authors: Vashendriya V V Hira, Annique Loncq de Jong, Klea Ferro...

Immunohistochemistry (IHC) specifically localizes proteins in cells and tissues, but methodologies vary widely. Therefore, we performed a methodological IHC optimization and validation study. First, we compared advantages and disadvantages of cryostat sections versus paraffin sections. Second, we compared and optimized antigen retrieval in paraffin sections using citrate buffer and Tris/EDTA buffer. Third, aminoethyl carbazole (AEC) and 3,3'-diaminobenzidine (DAB) were tested as horseradish peroxidase (HRP) substrates to obtain a water-insoluble coloured end product to visualize antigens. Fourth, secondary antibodies conjugated with either mono-HRP or poly-HRP were compared. The study was performed using serial sections of human tonsil. IHC was performed with primary antibodies against endothelial cell marker CD31, smooth muscle actin (SMA), chemokine stromal-derived factor-1α (SDF-1α) and its receptor C-X-C receptor type 4 (CXCR4), macrophage marker CD68 and proliferation marker Ki67. DAB rather than AEC, and cryostat sections rather than paraffin sections gave optimum staining at highest primary antibody dilutions, whereas tissue morphology in paraffin sections was superior. Loss of antigenicity in paraffin sections by formaldehyde fixation, heat and/or masking of epitopes was counteracted by antigen retrieval but not for all antigens. Two out of six antigens (CD31 and CD68) could not be retrieved irrespective time and type of retrieval. Tris-EDTA was superior to citrate buffer for antigen retrieval. The use of mono-HRP or poly-HRP depended on the affinity of the primary antibody for its antigen. We conclude that IHC methodology optimization and validation are crucial steps for each antibody and each research question.

Topics: Antigens; Biomarkers; Formaldehyde; Frozen Sections; Humans; Immunohistochemistry; Paraffin; Paraffin Embedding; Staining and Labeling; Tissue Fixation

PubMed: 30454859
DOI: 10.1016/j.acthis.2018.10.011

Review

Authors: Joachim Weis, Sebastian Brandner, Martin Lammens...

Nerve biopsy is a valuable tool in the diagnostic work-up of peripheral neuropathies. Currently, major indications include interstitial pathologies such as suspected vasculitis and amyloidosis, atypical cases of inflammatory neuropathy and the differential diagnosis of hereditary neuropathies that cannot be specified otherwise. However, surgical removal of a piece of nerve causes a sensory deficit and - in some cases - chronic pain. Therefore, a nerve biopsy is usually performed only when other clinical, laboratory and electrophysiological methods have failed to clarify the cause of disease. The neuropathological work-up should include at least paraffin and resin semithin histology using a panel of conventional and immunohistochemical stains. Cryostat section staining, teased fiber preparations, electron microscopy and molecular genetic analyses are potentially useful additional methods in a subset of cases. Being performed, processed and read by experienced physicians and technicians nerve biopsies can provide important information relevant for clinical management.

Topics: Biopsy; Histocytological Preparation Techniques; Humans; Neurology; Pathology, Clinical; Peripheral Nerves; Peripheral Nervous System Diseases; Practice Guidelines as Topic; Specimen Handling

PubMed: 22192700
DOI: 10.5414/np300468

Authors: Frederik Thiele, Thomas Hummel, Adam N McCaughan...

Quantum photonic processing via electro-optic components typically requires electronic links across different operation environments, especially when interfacing cryogenic components such as superconducting single photon detectors with room-temperature control and readout electronics. However, readout and driving electronics can introduce detrimental parasitic effects. Here we show an all-optical control and readout of a superconducting nanowire single photon detector (SNSPD), completely electrically decoupled from room temperature electronics. We provide the operation power for the superconducting detector via a cryogenic photodiode, and readout single photon detection signals via a cryogenic electro-optic modulator in the same cryostat. This method opens the possibility for control and readout of superconducting circuits, and feedforward for photonic quantum computing.

PubMed: 37859067
DOI: 10.1364/OE.492035