Ergonomic considerations are key to the success of ultrasound-guided diagnostics [1] and medical interventions that require very fine control. Head movements in particular may inconvenience surgeons and result in technical difficulties, and there remains a significant failure rate for first pass interventions. Wearable devices that can be attached to smart glasses, consisting of a head-mounted display which projects the ultrasound screen in front of the operator’s eye, allow surgeons to keep their eyes and attention fixed on the surgical field. Research has shown that such smart glasses, which are both ergonomic and affordable, can improve the success rate of ultrasound-guided procedures.

Various studies in the last few years have contributed to highlighting the benefits of such smart glasses. A 2019 study first assessed the use of smart glasses in the context of ultrasound-guided peripheral venous access [2]. The research was carried out as a randomized, crossover-design simulation study in which emergency medicine residents attempted ultrasound-guided peripheral venous access on a pediatric patient with or without the use of smart glasses. Results demonstrated that the use of smart glasses, though not improving procedural time or the number of skin punctures and needle restrictions, significantly reduced the number of operator head movements.

A study shortly thereafter in 2020 examined the use of smart glasses equipped with augmented reality representing ultrasound information, alongside other real-time data such as endoscopic data [3]. The findings suggested that augmented reality can improve trauma surgery interventions. In particular, it improved the efficiency of surgery, reducing the operating time and minimizing the radiation exposure of clinical personnel and patients alike.

Most recently, a study from 2021 looked into the success rate of ultrasound-guided pediatric radial arterial catheterization [4]. The work was carried out as a prospective, single-blinded, randomized controlled, single-center study focused on pediatric patients under 2 years of age requiring radial artery cannulation under general anesthesia. Results demonstrated that smart glasses-assisted ultrasound-guided radial artery catheterization improved first-attempt success rates, procedure time, and overall complication rates. It also improved ergonomic satisfaction.

Interestingly, the use of smart glasses is beginning to extend beyond ultrasound-guided procedures. A 2020 prospective, randomized study sought to assess the feasibility of using smart glasses in the context of fluoroscopically guided minimally invasive spinal instrumentation surgery [5]. The study, which examined posterior lumbar interbody fusion, found that smart glasses did not significantly reduce the number of surgeon head turns and both the operative and radiation exposure times. Additional studies will provide a more complete picture.

Research has shown that the use of smart glasses in ultrasound-guided procedures improves first-attempt success rates, enhances ergonomic ease, minimizes procedure time, and decreases complication rates. However, certain challenges remain. First, future research will need to focus on developing faster data transfer algorithms to achieve higher spatial and temporal resolutions. Second, the glasses can be heavy, and applied research will need to focus on developing lighter smart glasses. Finally, work is required to elucidate more in depth how smart glasses might affect patient safety and health care professionals in a range of complex care environments [6].

References 

1. Maas, S., Ingler, M. & Overhoff, H. M. Using smart glasses for ultrasound diagnostics. Curr. Dir. Biomed. Eng. (2015). doi:10.1515/cdbme-2015-0049
2. Lim, H. et al. Use of smart glasses for ultrasound-guided peripheral venous access: A randomized controlled pilot study. Clin. Exp. Emerg. Med. (2019). doi:10.15441/ceem.19.029
3. Lal, A., Hu, M. H., Lee, P. Y. & Wang, M. L. A novel approach of using AR and smart surgical glasses supported trauma care. arXiv (2020).
4. Jang, Y. E. et al. Smart Glasses for Radial Arterial Catheterization in Pediatric Patients: A Randomized Clinical Trial. Anesthesiology (2021). doi:10.1097/ALN.0000000000003914
5. Matsukawa, K. & Yato, Y. Smart glasses display device for fluoroscopically guided minimally invasive spinal instrumentation surgery: A preliminary study. J. Neurosurg. Spine (2021). doi:10.3171/2020.6.SPINE20644
6. Romare, C. & Skär, L. Smart glasses for caring situations in complex care environments: Scoping review. JMIR mHealth and uHealth (2020). doi:10.2196/16055

Over 100,000 people currently sit on organ transplant waitlists ¹; about 6,000 die annually while waiting for a kidney, heart or lung. Xenotransplantation, a procedure involving transplants of live nonhuman cells, tissues, or organs (or such human tissues that have come into ex vivo contact with live nonhuman tissues) into humans, is thus of tremendous clinical promise and potential. While not a novel method – many clinical xenotransplantation attempts have been made in the last few centuries ², the challenges of xenotransplantation are significant but being steadily being overcome.

Despite its considerable benefits, nonhuman tissue transplants present a significant risk in light of the potential infection of recipients with foreign infectious agents, in addition to their potential transmission to the general human population ³. Advances in gene-editing tools (for example, genetically engineering pigs to make their tissues more resistant to human immune responses) and immunosuppressive therapy have particularly contributed to making clinical xenotransplantation more viable.

A number of xenotransplantation successes have been documented between nonhuman animals. In preliminary research studies, a life-supporting genetically engineered pig kidney functioned in a monkey for over a year ⁴, and genetically engineered orthotopically-placed pig hearts have maintained the lives of baboons for 6 months ⁵.

Xenotransplantation has also been met with budding success from nonhuman animal cells, tissues, and organs to humans. Pig cells have been a particularly viable transplantation agent to this end. Pig pancreatic islets can be used to treat diabetes, for example, while fetal porcine neural stem cells can be applied to Parkinson cell therapy. In parallel, pig skin can be transplanted to help burn victims ³.

1905 saw the first serious attempt at organ xenotransplantation, when slices of rabbit kidney were transplanted into a child with chronic kidney disease who was dying of renal insufficiency ⁶. The two first decades of the 20th century consequently saw a flurry of subsequent xenotransplantation efforts involving primate, pig and lamb organs, among others.

This culminated in the successful transplantation, in 1997, of a pig’s heart, lungs and kidneys into a terminally ill individual in India. The patient was a 32-year-old man who had failed to respond to conventional surgery; he remarkably survived for 7 days, dying thereafter from multiple infections ⁷.

The last few years saw another series of xenotransplantation breakthroughs. In 2021, a pig kidney was successfully transplanted into a brain-dead recipient. Partly because the pig’s thymus gland was transplanted as well, there were no indications of immediate immune rejection ⁸.

Most recently, in 2022, a 57-year-old successfully survived a surgery in which he received a heart from a 1-year-old pig in which the enzymes underpinning the production of hyperacute organ rejection antigens had been gene-edited out. The U.S. medical regulator granted special permission for the procedure, which is not currently approved, given that the patient would have otherwise died – and the surgery marked the first of its kind ⁹.

Since preclinical studies in nonhuman primates can take up to 4 years and are relatively expensive, 3D bioprinting has emerged as a particularly promising technology in this context ¹⁰. In particular, the scaffold-free 3D-bioprinting of pig organ models using genetically engineered pig cells can quickly and cheaply generate organ-specific 3D models. In parallel, organ-specific bioprinting can also be used to better understand different immunogenic responses, helping to advance the field of nonhuman tissue transplants ¹¹.

Ethical questions surrounding the clinical use of nonhuman tissue for transplants are being raised worldwide – to which end the U.S. Food and Drug Administration published comprehensive guidelines in 2003 ¹². While it remains unclear what type of evidence is considered sufficient, national regulatory authorities must shape regulations such as to enable safe, thorough, informative clinical trials well supported by preclinical data.

Recent clinical breakthroughs have been paving the way for the future of xenotransplantation, marking a step forward toward solving the problem of human organ shortage ¹³.

References

1. Organ Donation Statistics | organdonor.gov. Available at: https://www.organdonor.gov/learn/organ-donation-statistics.
2. Deschamps, J. Y., Roux, F. A., Saï, P. & Gouin, E. History of xenotransplantation. Xenotransplantation (2005). doi:10.1111/j.1399-3089.2004.00199.x
3. Xenotransplantation | FDA. Available at: https://www.fda.gov/vaccines-blood-biologics/xenotransplantation.
4. Kim, S. C. et al. Long-term survival of pig-to-rhesus macaque renal xenografts is dependent on CD4 T cell depletion. Am. J. Transplant. (2019). doi:10.1111/ajt.15329
5. Längin, M. et al. Consistent success in life-supporting porcine cardiac xenotransplantation. Nature (2018). doi:10.1038/s41586-018-0765-z
6. Toledo-Pereyra, L. H. & Lopez-Neblina, F. Xenotransplantation: a view to the past and an unrealized promise to the future. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation (2003). doi:10.1034/j.1399-0039.2002.00003.x
7. Why the US Pig Heart Transplant Was Different From the 1997 Assam Doc’s Surgery – The Wire Science. Available at: https://science.thewire.in/the-sciences/university-maryland-pig-heart-xenotransplant-dhani-ram-baruah-1997-failed-surgery-arrest/.
8. Progress in Xenotransplantation Opens Door to New Supply of Critically Needed Organs | NYU Langone News. Available at: https://nyulangone.org/news/progress-xenotransplantation-opens-door-new-supply-critically-needed-organs.
9. Man gets genetically-modified pig heart in world-first transplant – BBC News. Available at: https://www.bbc.com/news/world-us-canada-59944889.
10. Cooper, D. K. C. Financial support for xenotransplantation research. Xenotransplantation (2019). doi:10.1111/xen.12483
11. Li, P. et al. The potential role of 3D-bioprinting in xenotransplantation. Current Opinion in Organ Transplantation (2019). doi:10.1097/MOT.0000000000000684
12. Tissue Guidances | FDA. Available at: https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/tissue-guidances.
13. Lu, T., Yang, B., Wang, R. & Qin, C. Xenotransplantation: Current Status in Preclinical Research. Frontiers in Immunology (2020). doi:10.3389/fimmu.2019.03060

The Janus tyrosine kinase (JAK) family of proteins are cytoplasmic non-receptor tyrosine kinases that are expressed in all cells and are critical for development, immunity, and other cellular processes [1]. The four members of the JAK family – JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2) – bind to and phosphorylate (activate) cytokine receptors, enabling the binding of signaling molecules such as those belonging to the signal transducer and activator of transcription (STAT) family [2]. The JAK-STAT pathway was first described in 1992 and borrows its name from Janus, the two-faced Roman god, on account of JAKs having two phosphate-transferring domains [3]. Now, Janus kinase inhibitors are being studied as treatment options for COVID-19.

The JAK-STAT pathway is active during the body’s immune response and leads to the production of proinflammatory cytokines. Cytokines, such as interleukins and tumor necrosis factors, target pathogens and recruit leukocytes to the site of infection/injury. However, the JAK-STAT pathway can become overactive in response to infection, causing cytokine release syndrome (CRS, known colloquially as a “cytokine storm”), a condition whereby the overproduction of cytokines may lead to sepsis and other life-threatening conditions [4]. CRS has been reported to occur in some patients with severe cases of COVID-19 [5], and inhibiting the JAK-STAT pathway thus represents one potential approach to limiting the immune overreaction inducted by COVID-19.

JAK inhibitors target at least one of the JAK family members and are used for several different immune-related complications. For example, the JAK inhibitor ruxolitinib binds to and inhibits JAK1 and JAK2 and is administered to patients with myelofibrosis and polycythemia [6]. Janus kinase inhibitors seem to also reduce the hyperinflammation caused by COVID-19. Several cases in the literature report that ruxolitinib reduces mortality in severe cases of COVID-19 [7]. Baricitinib, a JAK inhibitor that also interferes with JAK1 and JAK2 and is used to treat the effects of rheumatoid arthritis, has also found success in treating the inflammatory side-effects of COVID-19. Unlike ruxolitinib, baricitinib also binds the cyclin G-associated kinase, a protein that regulates endocytosis [8]. Endocytosis is the process by which the SARS-CoV-2 virus enters lung cells, which may allow baricitinib to prevent further infection of lung cells in COVID-19 patients.

To better quantify the efficacy of Janus kinase inhibitors like ruxolitinib and baricitinib in reducing hyperinflammation from COVID-19, several researchers have conducted analyses of data on administering JAK inhibitors to COVID-19 patients. Chen et al. found that both ruxolitinib and baricitinib reduced the use of invasive mechanical ventilation but did not affect the length of hospitalization or rates of ICU admission [5]. Wijaya et al. similarly found that JAK inhibitors (including ruxolitinib, baricitinib, tofacitinib, and fedracitinib) reduced mortality levels but not risk of clinical deterioration [9]. An analysis comparing the relative efficacy of the various JAK inhibitors has not yet been conducted, though the NIH recommends baricitinib or tofacitinib over the others due to trials that showed their efficacy [10].

Bruton’s tyrosine kinase (BTK) is a kinase that is involved in the development of B cells and cytokine receptor pathways. The NIH COVID-19 Treatment Panel currently recommends against BTK inhibitors due to insufficient data. BTK inhibitors include acalabrutinib, which is used to treat B-cell malignancies such as chronic lymphocytic leukemia [11], and ibrutinib, which prevents graft-versus-host disease in stem cell transplant patients [12]. Both also reduce the signaling associated with inflammation, making them promising research avenues in the search for additional COVID-19 therapeutics.

References 

1. Schonhofer, C., Coatsworth, H., Caicedo, P., Ocampo, C. & Lowenberger, C. Chapter 10 – Aedes aegypti Immune Responses to Dengue Virus. in Lessons in Immunity (eds. Ballarin, L. & Cammarata, M.) 129–143 (Academic Press, 2016). doi:10.1016/B978-0-12-803252-7.00010-2.
2. Yamaoka, K. et al. The Janus kinases (Jaks). Genome Biol. 5, 253 (2004).
3. Seif, F. et al. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun. Signal. 15, 23 (2017).
4. Ragab, D., Salah Eldin, H., Taeimah, M., Khattab, R. & Salem, R. The COVID-19 Cytokine Storm; What We Know So Far. Front. Immunol. 11, 1446 (2020).
5. Chen, C. et al. JAK-inhibitors for coronavirus disease-2019 (COVID-19): a meta-analysis. Leukemia 35, 2616–2620 (2021).
6. PubChem. Ruxolitinib. https://pubchem.ncbi.nlm.nih.gov/compound/25126798.
7. D’Alessio, A. et al. Low-dose ruxolitinib plus steroid in severe SARS-CoV-2 pneumonia. Leukemia 35, 635–638 (2021).
8. Richardson, P. et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet Lond. Engl. 395, e30–e31 (2020).
9. Wijaya, I. et al. The use of Janus Kinase inhibitors in hospitalized patients with COVID-19: Systematic review and meta-analysis. Clin. Epidemiol. Glob. Health 11, 100755 (2021).
10. Kinase Inhibitors. COVID-19 Treatment Guidelines https://www.covid19treatmentguidelines.nih.gov/therapies/immunomodulators/kinase-inhibitors/.
11. Owen, C., Berinstein, N. L., Christofides, A. & Sehn, L. H. Review of Bruton tyrosine kinase inhibitors for the treatment of relapsed or refractory mantle cell lymphoma. Curr. Oncol. Tor. Ont 26, e233–e240 (2019).
12. Research, C. for D. E. and. FDA expands ibrutinib indications to chronic GVHD. FDA (2019).

The top three carbon emitters, the United States, China, and the European Union, contribute over half (56%) of the world’s total healthcare climate footprint [1]. Within the United States, the healthcare system is estimated to account for about 8.5% of the carbon dioxide emitted annually. The World Health Organization estimates that the costs of climate change’s direct damage to health will reach $2 to $4 billion annually by 2030: It is thus particularly important to minimize the compounding effects of heightened healthcare costs resulting from severe climate change effects on health by reducing the carbon footprint of healthcare in the first place. Ongoing operations in the healthcare setting in particular have a hefty carbon footprint, given their high demand for lighting, ventilation, heating, air conditioning, transport, and electronic equipment – representing a unique point of leverage to reduce environmental impact. 

First, it is key to minimize the use of healthcare resources, both in terms of infrastructure and personnel: Empowering patients to make the right decisions and develop healthy habits to minimize their need for healthcare in the first place is a cornerstone to reducing the use of medical resources. In parallel, any system of healthcare provider payment based on a fee-for-service model will influence healthcare providers to run more tests and use more resources than might be absolutely necessary – therefore, it may be important to adopt a system which minimizes any use of resources linked to a financial incentive. Second, in as much as possible, telemedicine should be utilized to improve efficiency and reduce pollution from transportation to and from sites. Routine check-ups and similar care can occur via teleconsultation without a loss in quality in many situations [2]. Further, the separation of elective surgery and emergency care facilities may maximize the efficient use of operating resources and beds; multi-purpose facilities for extended primary care teams could allow for better, cheaper, more environmentally sustainable healthcare delivery.  

As regards the ongoing operations of the healthcare system, indirect emissions from purchased energy sources such as electricity, steam, cooling, and heating account for 12% of the industry’s carbon footprint: It is therefore key to minimize their utilization, use them as efficiently as possible, and prioritize alternative energy generation. Hospitals can be built according to energy-efficient designs, and non-essential equipment can be switched off when not in use [3]. In addition, energy can be consumed and distributed more efficiently, with each unique medical specialty having its own opportunities and leverage points. Steps can also be taken to reduce, and recycle when possible, medical waste, food waste, and water use – all of which have a substantial impact at the institutional level.  

Outside the hospital, healthcare-related transportation should aim to make use of clean energy, such as through the use of hybrid or electric vehicles, in addition to collective methods of transportation such as shuttle services. Hospitals can also encourage active transport by installing bike parking and shower facilities while collaborating with local authorities on suitable routes, as well as carpooling and public transportation initiatives. 

Of course, optimal resource use will remain a difficult balance to strike. For example, the federal Occupational Health and Safety Administration is requiring hospitals to make hefty use of air purification systems to prevent the circulation COVID-19; however, this also increases energy use. “There are numerous other examples of where regulations compel hospitals to take actions that may not be aligned with efforts to decarbonize, but may be important to the care of patients or the safety of staff and others,” as explained by the chief operating officer of the American Hospital Association [4].  

Having pledged to cut United States greenhouse gas emissions by at least half by 2030, engaging the hospital industry will represent a core hurdle to the new Biden administration. Health, as every sector of society, has the responsibility to align itself with the global carbon reduction agenda in order to ensure a low-carbon, equitable, and healthy future. 

References 

1. Karliner, J., Slotterback, S., Boyd, R., Ashby, B. & Steele, K. Health care’s climate footprint: the health sector contribution and opportunities for action . Eur. J. Public Health. (2019). doi: 10.1093/eurpub/ckaa165.843  

1. Porter, M. E. What Is Value in Health Care? New Engl. J. Med. Perspect. Perspect. (2010). doi: 10.1056/NEJMp1011024  

1. Tomson, C. Reducing the carbon footprint of hospital-based care. Futur. Hosp. J. 2, 57 (2015). doi: 10.7861/futurehosp.2-1-57  

1. HHS will prod hospitals to cut carbon emissions | Modern Healthcare. Available at: https://www.modernhealthcare.com/politics-policy/hhs-will-prod-hospitals-cut-carbon-emissions. 

The healthcare system is estimated to account for up to 8.5% of the carbon dioxide emitted annually in the United States (1), and from 2010 to 2018, American greenhouse gas emissions increased by 6%, ranking first among industrialized countries (2). Healthcare supply chains generate the lion’s share of carbon emissions, representing nearly 80% (3), encompassing the production, transportation, use, and disposal of goods and services, including pharmaceuticals and other chemicals, food and agricultural products, medical devices, hospital equipment, and instruments. Decarbonizing this supply chain will be key to curbing climate change.

The measurement of greenhouse gas emissions is a crucial first step toward identifying and reducing the impact of the most carbon-intensive epicenters (4). To this end for example, England’s National Health Service’s Carbon Reduction Strategy was successful in developing tools, including the Procuring for Carbon Reduction Toolkit, aiming to provide professionals with guidance and methods to identify and understand the carbon reduction opportunities within the scope of their organization (5). In addition, healthcare systems may seek to develop an online platform to track the carbon footprint of product usage and resource consumption in order to generate the requisite high-quality data to inform policy thereafter.

In addition to better understanding carbon emission hotspots in healthcare supply chains, it is important to reduce consumption in general. This can be encouraged by promoting healthy lifestyles and ensuring excellent patient education as regards nutrition, fitness, and health – all contributing to sustainable preventative medicine.

Second, it is important to facilitate the sustainable procurement of goods. For example, buyers should use life-cycle costing to select the best supplier. Life-cycle costs are linked to both the contracting authority and other users, as well as to quantifiable environmental and social externalities. Examples include the costs of pollution caused by raw materials extraction and climate change mitigation costs. To address this issue, the largest healthcare provider of Sweden’s Skåne county has been increasingly using products made from biomaterials with a low life-cycle cost to replace certain plastic materials. As the result of innovative procurement strategies, one supplier has developed more climate-friendly aprons using 91% renewable materials.

Further, the transportation of goods must be carefully considered: Emissions emanating directly from healthcare facilities and healthcare owned vehicles constitute 17% of the healthcare’s footprint. Therefore, local goods or goods transported via sustainable energy-fueled modes of transportation should be favored.

In parallel, goods can be used in a more green-friendly fashion, such as by using compostable materials and reducing single-use goods and unnecessary disposal. Iceland’s Landspitali National University Hospital’s Environmental Program has resulted in the hospital replacing Styrofoam boxes for take-away food with high-quality, BPA-free reusable boxes – leading to the reduction in use of 123,000 boxes annually. In addition, food waste is composted, and hospital employees can receive free compost to use for their own at-home gardening.

To ensure that all stakeholders remain well-informed with regard to how best to reduce the carbon footprint of healthcare supply chains, it is important to ensure access to information and comprehensive training programs for staff. In the meantime, all healthcare sector personnel should continue to share ideas and highlight any opportunities for greater collaboration across stakeholders and programs. Decarbonizing the United States supply chain will require a progressive mentality shift alongside a broad range of policies aimed at supporting and rewarding sustainable innovations at all levels.

References 

1. U.S. Health System Will Need to Adapt to Climate Change. Available at: https://www.commonwealthfund.org/blog/2018/be-high-performing-us-health-system-will-need-adapt-climate-change.
2. Eckelman, M. J.et al.Health care pollution and public health damage in the United States: An update. Health Aff. (2020). doi:10.1377/hlthaff.2020.01247 
3. Zhao, Q.et al.Global, regional, and national burden of mortality associated with non-optimal ambient temperatures from 2000 to 2019: a three-stage modelling study. Lancet Planet. Heal. (2021). doi:10.1016/S2542-5196(21)00081-4 
4. Hippocrates Data Center | Global Green and Healthy Hospitals. Available at: https://www.greenhospitals.net/hippocrates/.
5. NHS Sustainable Development Unit. Carbon Footprint update for NHS in England 2015.NHS Engl.(2016).