Background: Acute invasive fungal sinusitis (AIFS) is a highly fatal infection affecting immunocompromised patients. While defects in innate immunity have been studied as the primary focus in AIFS, adaptive immunity has yet to be explored in this condition.
Methods: Sinonasal biopsies from consenting surgical patients were collected from 13 AIFS patients, 8 immunocompromised patients without fungal infection, and 4 healthy controls. B- and T-cell receptor (BCR/TCR) sequences were reconstructed from bulk transcriptome sequencing. Clonal homeostasis, repertoire diversity, and V gene usage were compared for both BCRs and TCRs. Somatic hypermutation (SHM) rates, isotype distribution, and biophysical properties of BCRs were further analyzed. Lastly, bulk transcriptomic deconvolution was performed to examine the abundance of adaptive immune cells in AIFS.
Results: Both B and T cells in AIFS exhibited increased clonal expansion, coupled with decreased receptor diversity compared with control groups. V gene usage in BCRs and TCRs demonstrated immunosuppression-associated and AIFS-specific patterns. SHM was decreased in AIFS compared with both healthy and immunocompromised controls, particularly in IgG and IgA BCRs. The light and heavy chains of BCRs in AIFS were biophysically distinct from those of controls. Bulk deconvolution reveals depletion of naïve and memory B cells, as well as CD4 and CD8 T cells in AIFS compared with immunosuppressed controls.
Conclusions: Our results suggest that adaptive immunity is dysregulated in AIFS. Further studies should focus on single-cell profiling to further dissect the cellular dynamics underlying this dysregulation. Recombinant cytokine therapies to boost adaptive responses represent promising medical therapies to complement surgical debridement and antifungal medications.
Background: Endoscopic sinus surgery (ESS) fails to adequately address symptoms in some chronic rhinosinusitis (CRS) patients. This study aims to evaluate machine learning models (MLMs) in predicting ESS outcomes from preoperative data.
Methods: CRS patients who underwent primary ESS were used to train and test MLMs for the identification of the minimal clinically important difference (MCID) between pre- and post-operative total SNOT-22 scores. Fifty-nine preoperative predictors were included in the MLMs. Each model was optimized using K-fold cross validation. The performance of two MLMs and a conventional logistic regression (LR) model was evaluated.
Results: The study cohort constituted 242 patients. The Ensemble model achieved the highest discriminative performance (Ensemble area-under-the-curve [AUC] 0.89, 95% CI 0.87-0.91; LR AUC 0.85, 95% CI 0.83-0.87; XGBoost AUC 0.74, 95% CI 0.72-0.76, p < 0.05) and accuracy (Ensemble 87.8%; LR 81.6%; XGBoost 81.6%). The XGBoost model achieved the highest sensitivity (XGBoost 97.1%; LR 76.5%; Ensemble 85.3%) but poorer specificity (XGBoost 46.7%; LR 93.3%; Ensemble 93.3%). The most predictive factors in the Ensemble model were age, preoperative SNOT-22 and Patient Health Questionnaire 2 (PHQ-2) scores, nasal obstruction, and facial pain/pressure.
Conclusion: The Ensemble MLM achieved the highest overall accuracy and discriminative performance and matched LR for the highest specificity, suggesting that this model could be used in clinical decision-making to "rule in" patients likely to achieve MCID after ESS. This is the highest performance achieved in an MLM trained toward clinical outcomes in CRS. After validation in a multicenter cohort, the Ensemble MLM could become a useful adjunct in clinical decision-making for ESS.
Background: Regional anesthesia is effective in alleviating postoperative pain and reducing the requirement for systemic pain medications. However, optimal postoperative pain management in endoscopic sinus surgery (ESS) remains challenging. This study investigated the potential pain-reducing outcomes of general anesthesia combined with a bupivacaine injection at the sphenopalatine ganglion (SPG) and an anterior ethmoid nerve block following ESS.
Methods: A double-blind randomized controlled trial that included 80 patients (18-75 years old) with chronic rhinosinusitis who underwent ESS was conducted. Either 0.5% bupivacaine or normal saline was injected into the anterior ethmoid nerve and SPG. The visual analog scale (VAS) pain score was assessed at 0, 1, 2, 4, 6, 8, 12, and 24 h following the surgical procedure. The timing of analgesic administration and any postoperative adverse effects of 0.5% bupivacaine were recorded.
Results: The VAS scores were significantly improved in the bupivacaine group at 1 h (95% confidence interval [CI] = 0.77-3.81, p = 0.004), 2 h (95% CI = 1.00-3.47, p = 0.001), 4 h (95% CI = 0.59-2.38, p = 0.002), and 6 h (95% CI = 0.22-2.28, p = 0.0019). Overall, the results showed a significant difference (95% CI = 0.51-1.74, p < 0.001).
Conclusions: Postoperative endoscopic SPG and anterior ethmoid nerve blocks with bupivacaine effectively reduce postoperative pain and minimize analgesic requirements after ESS.
Chronic rhinosinusitis (CRS) may require endoscopic sinus surgery (ESS) as a complement to medical therapies. Type 2 dominant inflammation underlies nasal polyposis (CRSwNP), and is characterized by eosinophilic inflammation, poor therapeutic response, and high recurrence risk. Type 2 inflammation was defined as eosinophilic CRS (ECRS) based on clinical presentation and laboratory findings. Unfavorable wound healing, associated with elevated levels of matrix metalloproteinase 9 (MMP-9), can lead to failure of ESS. Doxycycline with its antibiotic, anti-inflammatory, and anti-protease (including MMP-9) properties may improve postoperative healing.
Thirty-three adult CRS patients scheduled for ESS were randomly assigned to receive either doxycycline or placebo for 56 days postoperative and were followed up until 48 weeks post-ESS. Postoperative wound healing was assessed endoscopically. Nasal secretions, serum, and patient-reported outcome measures were collected throughout the study. Nasal secretions were analyzed to monitor local myeloperoxidase (MPO), MMP-9, eosinophilic cationic protein (ECP), and IgE levels from baseline until 48 weeks post-ESS. Proteomics analysis, using LC-MS/MS, of nasal secretions was performed at baseline, 2- and 8-weeks post-ESS to investigate wound healing mechanisms.
Postoperative doxycycline significantly improved wound healing quality in patients with CRSwNP or ECRS. Increased local MMP-9, neutrophilic (MPO), and eosinophilic (ECP) inflammation post-ESS was dampened by doxycycline. Wound healing and extracellular matrix remodeling processes were upregulated by doxycycline treatment. In contrast, the placebo group showed increased neutrophilic inflammation and delayed healing.
Postoperative doxycycline therapy facilitated wound healing in CRSwNP and ECRS patients and suppressed local mucosal inflammation.
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