Tuft cells in the pathogenesis of chronic rhinosinusitis with nasal polyps and asthma.

OBJECTIVE: To review the latest discoveries regarding the role of tuft cells in the pathogenesis of chronic rhinosinusitis (CRS) with nasal polyposis and asthma. DATA SOURCES: Reviews and primary research manuscripts were identified from PubMed, Google, and bioRxiv using the search words airway epithelium, nasal polyposis, CRS or asthma and chemoreceptor cell, solitary chemosensory cell, brush cell, microvillus cell, and tuft cell. STUDY SELECTIONS: Studies were selected on the basis of novelty and likely relevance to the functions of tuft cells in chronic inflammatory diseases in the upper and lower airways. RESULTS: Tuft cells coordinate a variety of immune responses throughout the body. After the activation of bitter-taste receptors, tuft cells coordinate the secretion of antimicrobial products by adjacent epithelial cells and initiate the calcium-dependent release of acetylcholine resulting in neurogenic inflammation, including mast cell degranulation and plasma extravasation. Tuft cells are also the dominant source of interleukin-25 and a significant source of cysteinyl leukotrienes that play a role in initiating inflammatory processes in the airway. Tuft cells have also been found to seem de novo in the distal airway after a viral infection, implicating these cells in dysplastic remodeling in the distal lung in the pathogenesis of asthma. CONCLUSION: Tuft cells bridge innate and adaptive immunes responses and play an upstream role in initiating type 2 inflammation in the upper and possibly the lower airway. The role of tuft cells in respiratory pathophysiology must be further investigated, because tuft cells are putative high-value therapeutic targets for novel therapeutics in CRS with nasal polyps and asthma.

Medical malpractice in robotic surgery: a Westlaw database analysis.

Malpractice claims involving robot-assisted surgical procedures have increased more than 250% in the past 7 years compared to the seven years prior. We examined robotic surgery malpractice claims to identify trends in claimed liabilities, describe legal outcomes, and determine strategies to minimize future litigation. The Westlaw legal database was queried retrospectively for U.S. state and federal trials regarding robot-assisted surgical procedures from 2006 to 2013 and 2014 to 2021. Data abstracted from verdict reports included year, state, court type, defendant specialty, procedure performed, claimed injuries and liabilities, verdict, and damage amount awarded. Sixty-one cases across 25 states were identified, 16 cases between 2006 and 2013, and 45 from 2014 to 2021. Among those 45 cases, defendant verdicts predominated (n = 35, 77.8%), with only four plaintiff verdicts (8.9%) and six settlements (13.3%). Overall, 169 liabilities were claimed, most commonly negligent surgery (82.2%), misdiagnosis/failure to diagnose (46.7%), delayed treatment (35.6%), and lack of informed consent (31.1%). Thirteen cases resulted in indemnity payments (mean = $1,251,274), with damages ranging from $10,087 (infection and retained foreign body) to $5,008,922 (patient death). Hysterectomy (n = 19, 42.2%) was the most commonly litigated surgery, followed by prostatectomy (n = 5) and hernia repair (n = 4). The most litigated specialties were obstetrics/gynecology (48.9%), general surgery (28.9%), and urology (15.6%). Malpractice litigation in robot-assisted surgery is infrequent. As robotic procedures become more commonplace, surgeons must keep common liabilities in mind, as there are valuable and actionable lessons to be learned from these cases. Malpractice reform, continuing medical education activities, and improved informed consent protocols may help minimize future litigation.

Microbial metabolite succinate activates solitary chemosensory cells in the human sinonasal epithelium.

BACKGROUND: Succinate, although most famous for its role in the Krebs cycle, can be released extracellularly as a signal of cellular distress, particularly in situations of metabolic stress and inflammation. Solitary chemosensory cells (SCCs) express SUCNR1, the succinate receptor, and modulate type 2 inflammatory responses in helminth and protozoal infections in the small intestine. SCCs are the dominant epithelial source of interleukin-25, as well as an important source of cysteinyl leukotrienes in the airway, and have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis (CRS) and asthma. METHODS: In this study, we used scRNAseq analysis, live cell imaging of intracellular calcium from primary sinonasal air-liquid interface (ALI) cultures from 1 donor, and measure antimicrobial peptide release from 5 donors to demonstrate preliminary evidence suggesting that succinate can act as a stimulant of SCCs in the human sinonasal epithelium. RESULTS: Results from scRNAseq analysis show that approximately 10% of the SCC/ionocyte cluster of cells expressed SUCNR1 as well as a small population of immune cells. Using live cell imaging of intracellular calcium, we also demonstrate that clusters of cells on primary sinonasal ALI cultures initiated calcium-mediated signaling in response to succinate stimulation. Furthermore, we present evidence that primary sinonasal ALI cultures treated with succinate had increased levels of apical beta-defensin 2, an antimicrobial peptide, compared to treatment with a control solution. CONCLUSION: Overall, these findings demonstrate the need for further investigation into the activation of the sinonasal epithelium by succinate in the pathogenesis of CRS.

Smell and taste changes are early indicators of the COVID-19 pandemic and political decision effectiveness.

In response to the COVID-19 pandemic, many governments have taken drastic measures to avoid an overflow of intensive care units. Accurate metrics of disease spread are critical for the reopening strategies. Here, we show that self-reports of smell/taste changes are more closely associated with hospital overload and are earlier markers of the spread of infection of SARS-CoV-2 than current governmental indicators. We also report a decrease in self-reports of new onset smell/taste changes as early as 5 days after lockdown enforcement. Cross-country comparisons demonstrate that countries that adopted the most stringent lockdown measures had faster declines in new reports of smell/taste changes following lockdown than a country that adopted less stringent lockdown measures. We propose that an increase in the incidence of sudden smell and taste change in the general population may be used as an indicator of COVID-19 spread in the population.