OBJECTIVE: Frailty refers to a state of reduced physiological reserve and functional decline. We sought to analyse whether frailty, assessed using the 5-item modified frailty index (5mFI), was associated with increased morbidity and mortality following major mucosal head and neck surgery.
METHODS: We performed a retrospective study of patients undergoing major mucosal head and neck surgical resection over a 2-year period. Potential confounding variables were controlled by way of multivariable regression analysis.
RESULTS: There were 310 patients included with 77 (24.8 %) classified as frail. Most patients were male (219/310, 70.7 %), had a history of smoking (246/310, 79.4 %) and 151 patients (48.7 %) were older than 65 at time of surgery. Most surgeries related to oral cavity or oropharyngeal subsites (227/310, 73.2 %) and 150 patients (48.4 %) underwent microvascular free tissue reconstruction. On multivariable analysis, frail patients were more likely to suffer adverse outcomes such as a return to theatre (OR 3.47, 95 % CI 1.82-6.62, p < 0.001), a Clavien-Dindo grade IV complication (OR 6.23, 95 % CI 2.55-15.20, p < 0.001) or medical complications, such as respiratory complications (OR 2.61, 95 % CI 1.45-4.69; p = 0.001) or delirium (OR 5.05, 95 % CI 2.46-10.33; p < 0.001). Additionally, hospital length of stay was increased among frail patients (ß 16.46 days, 95 % CI 9.85-23.07 days; p < 0.001). Neither 90-day nor 1-year post-operative mortality was increased in frail patients.
CONCLUSIONS: Frailty assessed using the 5mFI was associated with greater post-operative morbidity, but not mortality following major mucosal head and neck surgery.

PURIFY-OBS-1 is an observational study evaluating the safety and efficacy of Seraph 100® Microbind Affinity Blood Filter (Seraph 100) use for COVID-19 patients with respiratory failure admitted to the intensive care unit (ICU). The Seraph 100 is a hemoperfusion device containing heparin-coated beads that can bind to, and reduce levels of, some circulating pathogens and inflammatory molecules. This study evaluated whether treatment with the Seraph 100 affected circulating and mucosal antibody levels in critically ill COVID-19 subjects. SARS-CoV-2 anti-spike and anti-nucleocapsid IgG and IgA levels in serum were evaluated at enrollment and on days 1, 4, 7, and 28 after Seraph 100 application, while anti-spike and nucleocapsid IgG, IgA, and secretory IgA levels in tracheal aspirates were evaluated at enrollment and on days 1, 2, 3, 7, and 28. Serum samples were also collected from the pre- and post-filter lines at 1 and 4 h following Seraph 100 application to evaluate the direct impact of the filter on circulating antibody levels. Treatment with the Seraph 100 did not alter the levels of circulating or mucosal antibodies in critically ill COVID-19 subjects admitted to the ICU.

We administered a questionnaire to participants who received different vaccination regimens to evaluate the effectiveness of Ad5-vectored COVID-19 vaccines. The results showed that administration of intramuscular Ad5-nCoV provided 21.32% more protection against SARS-CoV-2 infection than that of the inactivated COVID-19 vaccine in people who had received only one type of COVID-19 vaccine. Furthermore, aerosolized Ad5-nCoV exhibited good protection, whether it was administered as a homologous booster to people vaccinated with the intramuscular Ad5-nCoV or as a heterologous booster to people vaccinated with inactivated COVID-19 vaccines. Our research indicates that Ad5-nCoV is an effective booster. This finding supports the future selection of COVID-19 immunization strategies.

Cutaneous leishmaniasis is atypical in Sri Lanka because Leishmania donovani, which typically causes visceral disease, is the causative agent. The origins of recently described hybrids between L. donovani and other Leishmania spp. usually responsible for cutaneous leishmaniasis remain unknown. Other endemic dermotropic Leishmania spp. have not been reported in Sri Lanka. Genome analysis of 27 clinical isolates from Sri Lanka and 32 Old World Leishmania spp. strains found 8 patient isolates clustered with L. tropica and 19 with L. donovani. The L. tropica isolates from Sri Lanka shared markers with strain LtK26 reported decades ago in India, indicating they were not products of recent interspecies hybridization. Because L. tropica was isolated from patients with leishmaniasis in Sri Lanka, our findings indicate L. donovani is not the only cause of cutaneous leishmaniasis in Sri Lanka and potentially explains a haplotype that led to interspecies dermotropic L. donovani hybrids.

BACKGROUND: Adjuvant therapy has improved the clinical prognosis for postoperative melanoma patients. However, the long-term efficacy of this therapy on the melanoma acral and mucosal subtypes has not been fully evaluated in previous trials. This study assessed the 3-year recurrence-free survival and overall survival of patients with melanoma, including the acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or with the combination of the BRAF and MEK inhibitors dabrafenib and trametinib.
METHODS: We retrospectively analyzed both the 3-year time to relapse (TTR) and overall survival (OS) of 120 patients treated with anti-PD-1 antibody (Ab), or with the combination of dabrafenib and trametinib.
RESULTS: The overall median TTR was 18.4 months, with a range of 0.69 to 36 months. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. Baseline tumor thickness (TT) and acral type were associated with the TTR in subgroup analysis. Moreover, we classified 104 acral and non-acral cutaneous patients into the anti-PD-1 Abs or dabrafenib plus trametinib combined therapies cohort in multiple analyses. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type (p > 0.05).
CONCLUSIONS: This study suggests that adjuvant therapy is more effective with non-acral cutaneous melanoma than either the acral or mucosal types at the 3-year TTR endpoint.

BACKGROUND: The aim of our study was to investigate the prevalence of coexisting conditions and exposures in children with nodular tracheobronchitis diagnosed by flexible bronchoscopy.
METHODS: We conducted a single-center retrospective review of 100 children diagnosed with nodular tracheobronchitis by flexible bronchoscopy between 2012 and 2023.
RESULTS: Common coexisting diagnoses included gastroesophageal reflux disease (GERD, 50%), dysphagia/aspiration (40%), asthma (30%), recurrent croup (30%), tracheostomy dependence (19%) and eosinophilic esophagitis (EOE) (12%). Bronchoalveolar lavage (BAL) demonstrated cellular inflammation with elevated proportions of neutrophils in 63%, and lymphocytes in 24%. Among 88 patients in whom bacterial cultures were performed, 52% were positive, with Moraxella, Haemophilus, Streptococcal and Pseudomonas species predominating. Among 30 patients who underwent viral testing, 57% were positive, with rhinovirus (82%) and adenovirus (29%) predominating. Patients with neutrophilic inflammation were more likely to have a positive respiratory bacterial culture and/or viral polymerase chain reaction (p = 0.003, 0.005). Evaluation of the gastrointestinal tract included 79 patients with a history of esophagogastroduodenoscopy, 45 patients with a videofluoroscopic swallow study (VFSS), and 45 patients with multi-channel intraluminal impedance and pH testing. The majority of VFSS were abnormal (60%) demonstrating either laryngeal penetration (33%) or intratracheal aspiration (27%). Median pH reflux and impedance proximal reflux indices were 3.8% and 0.5% respectively.
CONCLUSIONS: Potential contributing factors in the pathophysiology of nodular tracheobronchitis include bacterial and viral infections, GERD, dysphagia/aspiration, and EOE. When nodular tracheobronchitis is observed during bronchoscopy, further evaluation to assess for these conditions should be considered.

BACKGROUND: Advancements in immunotherapy for recurrent head and neck cancer have necessitated a better understanding of salvage surgical outcomes. This study aimed to determine patterns of failure following salvage head and neck surgery.
METHODS: A retrospective cohort study was conducted of 280 patients who underwent salvage surgery for recurrent mucosal squamous cell carcinoma from 1997 to 2018. Cumulative incidence was calculated using the nonparametric Aalen-Johansen estimator. Time to recurrence (TTR) and overall survival (OS) were estimated using the Kaplan-Meier method and multivariable Cox proportional hazard models were used to evaluate associated factors.
RESULTS: The 2 and 5-year cumulative incidence rates of second recurrence were 48.3 % (95 % CI 42.4-54.3) and 54.9 % (95 % CI 48.9-60.8), respectively. At 5 years, second locoregional recurrence was twice as common as distant recurrence (41.5 % [95 % CI 35.6-47.4] vs. 21.7 % [95 % CI 16.8-26.6]). The median TTR was 21.1 months (95 % CI 4.4-34.8), which varied by site (38.2 larynx/hypopharynx, 13.9 oral cavity, 8.3 sinonasal, and 7.8 oropharynx, P=.0001). The median OS was 32.1 months (95 % CI 24.1-47.6) and was worse for patients who were Black (hazard ratio [HR] 2.15, 95 % CI 1.19-3.9), current smokers (HR 2.73, 95 % CI 1.53-4.88), former smokers (HR 2.00, 95 % CI 1.19-3.35), ≥ 60 years of age (HR 1.41, 95 % CI 1.01-1.97), or received multimodal primary therapy (HR 1.98, 95 % CI 1.26-3.13).
CONCLUSIONS: Rates of recurrence and mortality after salvage surgery were poor but worse for patients who were Black, older, smoked, had initial multimodal therapy, or had sinonasal or oropharyngeal cancers.

Intranasal M2SR (M2-deficient Single Replication influenza virus) vaccine induces robust immune responses in animal models and human subjects. A high-throughput multiplexed platform was used to analyze hemagglutinin-specific mucosal antibody responses in adults after a single dose of H3N2 M2SR. Nasal swab specimens were analyzed for total and hemagglutinin-specific IgA. Significant, dose-dependent increases in mucosal antibody responses to vaccine-matched and drifted H3N2 hemagglutinin were observed in M2SR vaccinated subjects regardless of baseline serum and mucosal immune status. These data suggest that M2SR induces broadly cross-reactive mucosal immune responses which may provide better protection against drifted and newly emerging influenza strains.

Despite advancements in treating cutaneous melanoma, patients with acral and mucosal (A/M) melanomas still have limited therapeutic options and poor prognoses. We analyzed 156 melanomas (101 cutaneous, 28 acral, and 27 mucosal) using the Foundation One cancer-gene specific clinical testing platform and identified new, potentially targetable genomic alterations (GAs) in specific anatomic sites of A/M melanomas. Using novel pre-clinical models of A/M melanoma, we demonstrate that several GAs and corresponding oncogenic pathways associated with cutaneous melanomas are similarly targetable in A/M melanomas. Other alterations, including MYC and CRKL amplifications, were unique to A/M melanomas and susceptible to indirect targeting using the BRD4 inhibitor JQ1 or Src/ABL inhibitor dasatinib, respectively. We further identified new, actionable A/M-specific alterations, including an inactivating NF2 fusion in a mucosal melanoma responsive to dasatinib in vivo. Our study highlights new molecular differences between cutaneous and A/M melanomas, and across different anatomic sites within A/M, which may change clinical testing and treatment paradigms for these rare melanomas.

Many pathogens enter the host through mucosal sites. Thus, interfering with pathogen entry through local neutralization at mucosal sites therefore is an effective strategy for preventing disease. Mucosally administered vaccines have the potential to induce protective immune responses at mucosal sites. This manuscript delves into some of the latest developments in mucosal vaccination, particularly focusing on advancements in adjuvant technologies and the role of these adjuvants in enhancing vaccine efficacy against respiratory pathogens. It highlights the anatomical and immunological complexities of the respiratory mucosal immune system, emphasizing the significance of mucosal secretory IgA and tissue-resident memory T cells in local immune responses. We further discuss the differences between immune responses induced through traditional parenteral vaccination approaches vs. mucosal administration strategies, and explore the protective advantages offered by immunization through mucosal routes.