Critical care in the developing world - a challenge for us all

The rapid economic growth in parts of the developing world is being accompanied by an expansion of critical care. Hurdles to expansion include lack of critical care training for healthcare workers. This is coupled with a need for a huge number of healthcare workers due to the high populations of countries such as China and India. Intensivists in the developed world can and should help

Surgical Helmets and SARS Infection

Performance testing of two brands of surgical helmets indicated that their efficiency at in vivo filtration of sub–micrometer-sized particles is inadequate for their use as respirators. These helmets are not marketed for respiratory protection and should not be used alone for protection against severe acute respiratory syndrome when performing aerosol-generating procedures

Is inhaled prophylactic heparin useful for prevention and management of pneumonia in ventilated ICU patients?

Purpose: The purpose was to determine the efficacy of prophylactic inhaled heparin for the prevention and treatment of pneumonia in patients receiving mechanical ventilation (MV)

Use of previous-day recalls of physical activity and sedentary behavior in epidemiologic studies: results from four instruments.

BACKGROUND: The last few years have seen renewed interest in use-of-time recalls in epidemiological studies, driven by a focus on the 24-h day [including sleep, sitting, and light physical activity (LPA)] rather than just moderate-vigorous physical activity (MVPA). This paper describes four different computerised use-of-time instruments (ACT24, PAR, MARCA and cpar24) and presents population time-use data from a collective sample of 8286 adults from different population studies conducted in Australia/New Zealand, Germany and the United States. METHODS: The instruments were developed independently but showed a number of similarities: they were self-administered through the web or used computer-assisted telephone interviews; all captured energy expenditure using variants of the Ainsworth Compendium; each had been validated against criterion measures; and they used a domain structure whereby activities were aggregated under categories such as Personal Care and Work. RESULTS: Estimates of physical activity level (average daily rate of energy expenditure in METs) ranged from 1.53 to 1.78 in the four studies, strikingly similar to population estimates derived from doubly labelled water. There was broad agreement in the amount of time spent in sleep (7.2-8.6 h), MVPA (1.6-3.1 h), personal care (1.6-2.4 h), and transportation (1.1-1.8 h). There were consistent sex differences, with women spending 28-81% more time on chores, 8-40% more time in LPA, and 3-39% less time in MVPA than men. CONCLUSIONS: Although there were many similarities between instruments, differences in operationalizing definitions of sedentary behaviour and LPA resulted in substantive differences in the amounts of time reported in sedentary and physically active behaviours. Future research should focus on deriving a core set of basic activities and associated energy expenditure estimates, an agreed classificatory hierarchy for the major behavioural and activity domains, and systems to capture relevant social and environmental contexts

Global outbreak research: harmony not hegemony

No abstract available

The story of critical care in Asia: a narrative review

Background Asia has more critically ill people than any other part of our planet. The aim of this article is to review the development of critical care as a specialty, critical care societies and education and research, the epidemiology of critical illness as well as epidemics and pandemics, accessibility and cost and quality of critical care, culture and end-of-life care, and future directions for critical care in Asia. Main body Although the first Asian intensive care units (ICUs) surfaced in the 1960s and the 1970s and specialisation started in the 1990s, multiple challenges still exist, including the lack of intensivists, critical care nurses, and respiratory therapists in many countries. This is aggravated by the brain drain of skilled ICU staff to high-income countries. Critical care societies have been integral to the development of the discipline and have increasingly contributed to critical care education, although critical care research is only just starting to take off through collaboration across groups. Sepsis, increasingly aggravated by multidrug resistance, contributes to a significant burden of critical illness, while epidemics and pandemics continue to haunt the continent intermittently. In particular, the coronavirus disease 2019 (COVID-19) has highlighted the central role of critical care in pandemic response. Accessibility to critical care is affected by lack of ICU beds and high costs, and quality of critical care is affected by limited capability for investigations and treatment in low- and middle-income countries. Meanwhile, there are clear cultural differences across countries, with considerable variations in end-of-life care. Demand for critical care will rise across the continent due to ageing populations and rising comorbidity burdens. Even as countries respond by increasing critical care capacity, the critical care community must continue to focus on training for ICU healthcare workers, processes anchored on evidence-based medicine, technology guided by feasibility and impact, research applicable to Asian and local settings, and rallying of governments for support for the specialty. Conclusions Critical care in Asia has progressed through the years, but multiple challenges remain. These challenges should be addressed through a collaborative approach across disciplines, ICUs, hospitals, societies, governments, and countries

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies