Emergency and postoperative access to critical and enhanced care: a multicentre prospective observational study.

Introduction: The ability to admit patients to enhanced or critical care may be limited by bed availability. In a network with low provision of critical and enhanced care beds, we aimed to assess the proportion of patients having surgery with moderate (1%-< 5%) or high (≥ 5%) predicted risk of 30-day postoperative mortality and their postoperative care location. We also aimed to study referral and admission outcomes to critical care.

Five historical innovations that have shaped modern otolaryngological surgery.

Throughout history, many innovations have contributed to the development of modern otolaryngological surgery, improving patient outcomes and expanding the range of treatment options available to patients. This article explores five key historical innovations that have shaped modern otolaryngological surgery: Operative Microscope, Hopkins Rigid Endoscope, Laryngeal Nerve monitoring, Cochlear implants and Laser surgery. The selection of innovations for inclusion in this article was meticulously determined through expert consensus and an extensive literature review.

Biomarkers in Prostate Cancer: A Review.

Background: Prostate cancer (PC) is the second most common cancer in men worldwide. It's the second leading cause cancer men in death. Prognostic tests based on molecular and biomarker analysis of tumor tissue may improve risk stratification of prostate cancer 2.

A metatranscriptomic evaluation of viruses in field-collected bed bugs.

Cimex lectularius, known as the common bed bug, is a widespread hematophagous human ectoparasite and urban pest that is not known to be a vector of any human infectious disease agents. However, few studies in the era of molecular biology have profiled the microorganisms harbored by field populations of bed bugs. The objective of this study was to examine the viruses present in a large sampling of common bed bugs and related bat bugs (Cimex pipistrelle).

Exosome-associated lysophosphatidic acid signaling contributes to cancer pain.

Pain associated with bone cancer remains poorly managed, and chemotherapeutic drugs used to treat cancer usually increase pain. The discovery of dual-acting drugs that reduce cancer and produce analgesia is an optimal approach. The mechanisms underlying bone cancer pain involve interactions between cancer cells and nociceptive neurons.

Association Between Combat-Related Traumatic Injury and Skeletal Health: Bone Mineral Density Loss Is Localized and Correlates With Altered Loading in Amputees: the Armed Services Trauma Rehabilitation Outcome (ADVANCE) Study.

The association between combat-related traumatic injury (CRTI) and bone health is uncertain. A disproportionate number of lower limb amputees from the Iraq and Afghanistan conflicts are diagnosed with osteopenia/osteoporosis, increasing lifetime risk of fragility fracture and challenging traditional osteoporosis treatment paradigms. The aim of this study is to test the hypotheses that CRTI results in a systemic reduction in bone mineral density (BMD) and that active traumatic lower limb amputees have localized BMD reduction, which is more prominent with higher level amputations.

ACLR and military service: time to rethink?

Anterior cruciate ligament (ACL) rupture is a common injury that affects young, active individuals, normally managed with reconstruction in this age group. Current UK Armed Forces policy precludes prospective applicants from joining with an anterior cruciate ligament reconstruction (ACLR). This isdue to the perceived risk of premature osteoarthritis (OA), graft rupture or clinical failure, all of which could make the service person medically non-deployable.

Total Synthesis of (±)-Aspidospermidine, (±)-Aspidofractinine, (±)-Limaspermidine, and (±)-Vincadifformine via a Cascade and Common Intermediate Strategy.

A concise strategy for the total synthesis of several alkaloids is reported. A Suzuki-Miyaura cross-coupling provides access to a 2-vinyl indole that undergoes a Diels-Alder cascade reaction with butyn-2-one to deliver a pyrroloindoline intermediate. This undergoes cascade amidation, reduction, skeletal rearrangement, and intramolecular Michael addition to provide a common intermediate containing the full framework of the alkaloids.

Phospholipase activity of acyloxyacyl hydrolase induces IL-22-producing CD1a-autoreactive T cells in individuals with psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by Th17 responses. Recent evidence has identified Langerhans cells to have a key role in disease pathogenesis, with constitutive high expression of CD1a and capacity to present lipid antigens to T cells. Phospholipase A enzymes generate neolipid antigens for recognition by CD1a-reactive T cells; however, the broader enzymatic pathways of CD1a lipid ligand generation have not been thoroughly investigated.

Hyaluronic Acid-Antibody Fragment Bioconjugates for Extended Ocular Pharmacokinetics.

Treatment of ocular diseases associated with neovascularization currently requires frequent intravitreal injections of antivascular endothelial growth factor (anti-VEGF) therapies. Reducing the required frequency of anti-VEGF injections and associated clinical visits may improve patient adherence to the prescribed treatment regimen and improve outcomes. Herein, we explore conjugation of rabbit and fragment antibodies (Fab) to the biopolymer hyaluronic acid (HA) as a half-life modifying strategy, and assess the impact on Fab biophysical properties and vitreal pharmacokinetics.

NMDA receptor modulation of glutamate release in activated neutrophils.

Background: Neutrophil depletion improves neurologic outcomes in experimental sepsis/brain injury. We hypothesized that neutrophils may exacerbate neuronal injury through the release of neurotoxic quantities of the neurotransmitter glutamate.

Methods: Real-time glutamate release by primary human neutrophils was determined using enzymatic biosensors.

Rapid Identification of Disulfide Bonds and Cysteine-Related Variants in an IgG1 Knob-into-Hole Bispecific Antibody Enhanced by Machine Learning.

Bispecific antibodies are regarded as the next generation of therapeutic modalities as they can simultaneously bind multiple targets, increasing the efficacy of treatments for several diseases and opening up previously unattainable treatment designs. Linking two half antibodies to form the knob-into-hole bispecific antibody requires an additional in vitro assembly step, starting with reduction of the antibodies and then reoxidization. Analysis of the disulfide bonds (DSBs) is vital to ensuring the correct assembly, stability, and higher-order structures of these important biomolecules because incorrect disulfide bond formation and/or presence of cysteine-related post-translational modifications can cause a loss of biological activity or even elicit an immune response from the host.

Uncontrolled sepsis: a systematic review of translational immunology studies in intensive care medicine.

Background: The design of clinical immunology studies in sepsis presents several fundamental challenges to improving the translational understanding of pathologic mechanisms. We undertook a systematic review of bed-to-benchside studies to test the hypothesis that variable clinical design methodologies used to investigate immunologic function in sepsis contribute to apparently conflicting laboratory data, and identify potential alternatives that overcome various obstacles to improve experimental design.

Methods: We performed a systematic review of the design methodology employed to study neutrophil function (respiratory burst), monocyte endotoxin tolerance and lymphocyte apoptosis in the intensive care setting, over the past 15 years.

Structure-Guided Design of an Anti-dengue Antibody Directed to a Non-immunodominant Epitope.

Dengue is the most common vector-borne viral disease, causing nearly 400 million infections yearly. Currently there are no approved therapies. Antibody epitopes that elicit weak humoral responses may not be accessible by conventional B cell panning methods.

Man is the new mouse: Elective surgery as a key translational model for multi-organ dysfunction and sepsis.

Translational research in critically ill human patients presents many methodological challenges. Diagnostic uncertainty, coupled with poorly defined comorbidities, make the identification of a suitable control population for case-control investigations an arguably insurmountable challenge. Healthy volunteer experiments using endotoxin infusion as an inflammatory model are methodologically robust, but fail to replicate the onset of, and diverse therapeutic interventions associated with, sepsis/trauma.

Simple tool for prediction of parotid gland sparing in intensity-modulated radiation therapy.

Sparing one or both parotid glands is a key goal when planning head and neck cancer radiation treatment. If the planning target volume (PTV) overlaps one or both parotid glands substantially, it may not be possible to achieve adequate gland sparing. This finding results in physicians revising their PTV contours after an intensity-modulated radiation therapy (IMRT) plan has been run and reduces workflow efficiency.

Cardiopulmonary exercise capacity and preoperative markers of inflammation.

Explanatory mechanisms for the association between poor exercise capacity and infections following surgery are underexplored. We hypothesized that aerobic fitness-assessed by cardiopulmonary exercise testing (CPET)-would be associated with circulating inflammatory markers, as quantified by the neutrophil-lymphocyte ratio (NLR) and monocyte subsets. The association between cardiopulmonary reserve and inflammation was tested by multivariable regression analysis with covariates including anaerobic threshold (AT) and malignancy.

Broadly neutralizing influenza hemagglutinin stem-specific antibody CR8020 targets residues that are prone to escape due to host selection pressure.

Broadly neutralizing antibodies (bNAb) that target a conserved region of a viral antigen hold significant therapeutic promise. CR8020 is a bNAb that targets the stem region of influenza A virus (IAV) hemagglutinin (HA). CR8020 is currently being evaluated for prophylactic use against group 2 IAVs in phase II studies.

Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes.

Background: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS.

Methods: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days.

Knowing the risk? NCEPOD 2011: a wake-up call for perioperative practice.

The high-risk surgical population comprises a minority of cases but accounts for the majority of postoperative complications and deaths. The most recent National Confidential Enquiry into Patient Outcome and Death review of these patients found highly variable standards of care and made several recommendations for change.

Mouse models for studying pain in sickle disease: effects of strain, age, and acuteness.

The clinical management of severe pain associated with sickle cell disease (SCD) remains challenging. Development of an optimal therapy would be facilitated by use of murine model(s) with varying degrees of sickling and pain tests that are most sensitive to vaso-occlusion. We found that young (≤3 months old) NY1DD and S+S(Antilles) mice (having modest and moderate sickle phenotype, respectively) exhibited evidence of deep tissue/musculoskeletal pain.

Tumor-evoked sensitization of C nociceptors: a role for endothelin.

Primary and metastatic cancers that effect bone are frequently associated with pain. Sensitization of primary afferent C nociceptors innervating tissue near the tumor likely contributes to the chronic pain and hyperalgesia accompanying this condition. This study focused on the role of the endogenous peptide endothelin-1 (ET-1) as a potential peripheral algogen implicated in the process of cancer pain.

Mental health status of Aboriginal and non-Aboriginal Australian prisoners.

Objective: To compare the mental health of Aboriginal and non-Aboriginal prisoners in New South Wales.

Methods: The sample consisted of a cross-sectional random sample of sentenced prisoners, and a consecutive sample of reception prisoners. The sample was drawn from 29 correctional centres (27 male, two female) across New South Wales.