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BMJ Open Apr 2023Curative intent treatment of head and neck cancer (HNC) is frequently radiation therapy over 7 weeks with concurrent chemotherapy. This regimen is effective but carries...
Efficacy of ketamine mouthwash in the management of oral and pharyngeal toxicity associated with head and neck chemoradiotherapy: protocol for a phase II, Simon's two-stage trial.
INTRODUCTION
Curative intent treatment of head and neck cancer (HNC) is frequently radiation therapy over 7 weeks with concurrent chemotherapy. This regimen is effective but carries a burden of toxicity leading to severe pain and treatment breaks portending inferior outcomes. Conventional palliation methods include opioids, anticonvulsants and local anaesthetics. Breakthrough toxicities are nevertheless ubiquitous and present an urgent unmet need. Ketamine is an inexpensive drug with mechanisms of analgesia outside the opioid pathway including N-methyl-D-aspartate (NMDA) receptor antagonism and a pharmacologically unique property of opioid desensitisation. Systemic ketamine is validated in randomised controlled trials for efficacy in reducing pain and/or opioid burden in the oncologic setting. Literature supports peripherally administered ketamine for pain control without systemic toxicity. These data support our rationale of using ketamine mouthwash to decrease acute toxicity of curative treatment of HNC, the efficacy of which is our aim to elucidate.
METHODS AND ANALYSIS
This is a phase II, Simon's two-stage trial. Patients have pathologically confirmed HNC and an intended regimen of 70 Gy of radiation with concurrent cisplatin. The protocol is initiated on diagnosis of grade 3 mucositis and consists of 2 weeks of 4 times daily (QID) ketamine mouthwash use. The primary endpoint is pain response defined as a combination of pain score and opioid use. 23 subjects will be enrolled in stage 1. If statistical criteria are met, 33 subjects will be enrolled in stage 2. Secondary endpoints include daily pain, daily opioid use, dysphagia at baseline and completion, nightly sleep quality, feeding tube placement and any unscheduled treatment breaks.
ETHICS AND DISSEMINATION
All trial data will be stored in an Institutional Review Board (IRB) approved database. The protocol is registered under Northwell IRB registration number #22-0292 and U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) approval has been granted under IND number 161609. Results are intended to be published in an open-source journal and further data, statistics and source documents are available on request.
TRIAL REGISTRATION NUMBER
NCT05331131.
Topics: United States; Humans; Ketamine; Analgesics, Opioid; Mouthwashes; Pain; Head and Neck Neoplasms; Chemoradiotherapy; Clinical Trials, Phase II as Topic
PubMed: 37041046
DOI: 10.1136/bmjopen-2022-064809 -
Indian Journal of Otolaryngology and... Mar 2023To investigate the effect of two-step of jaw-thrust technique on the placement of flexible laryngeal mask with both hands. 157 patients scheduled for functional...
To investigate the effect of two-step of jaw-thrust technique on the placement of flexible laryngeal mask with both hands. 157 patients scheduled for functional endoscopic sinus surgery were divided into two groups using a random number table method: control group (group C, n = 78) and test group (group T, n = 79). After induction of general anesthesia, the traditional method was applied to insert the flexible laryngeal airway mask in group C, and the two-step of jaw-thrust technique with both hands by the nurse was applied to help place the laryngeal mask in group T. The success rate, alignment status, oropharyngeal leak pressure (OLP) of the laryngeal mask, soft tissue injury of the oropharyngeal cavity and postoperative sore throat, and the incidence of adverse airway event were recorded in both groups. Results: The success rate of the first placement of flexible laryngeal masks in group C and group T were 73.8% and 97.5%, and the final success rates were 97.5% and 98.7%, respectively. Compared with group C, the success rate of first placement in group T was higher, and the difference was statistically significant ( < 0.01). There was no significant difference in the final success rate between the two groups ( = 0.56). The alignment score showed that the placement of group T was better than that of group C, and the difference was statistically significant ( < 0.01). The OLP of group C was 22.1 ± 2.6 cmHO, and the OLP of group T was 25.4 ± 3.8 cmHO. The OLP of group T was significantly higher than that of group C ( < 0.01). The incidence of mucosal injury and postoperative sore throat in group T were 2.5% and 5.0%, which were significantly lower than that of 23.0% and 16.7% in group C (both < 0.01). There was no adverse airway event in each group. Conclusion: The two-step of jaw-thrust technique with both hands can improve the success rate of the first placement of the flexible laryngeal mask and the positioning of the laryngeal mask, increase the sealing pressure of the laryngeal mask, and reduce the incidence of oropharyngeal soft tissue injury and postoperative pharyngeal pain.
PubMed: 37007892
DOI: 10.1007/s12070-022-03099-w -
Frontiers in Immunology 2023We describe a series of patients whose auto-immune bullous skin disease (AIBD) of the dermal-epidermal junction (DEJ) was characterized by clinical, immunological and...
INTRODUCTION
We describe a series of patients whose auto-immune bullous skin disease (AIBD) of the dermal-epidermal junction (DEJ) was characterized by clinical, immunological and ultrastructural features intermediate between bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP), and a recalcitrant course.
PATIENTS AND METHODS
From the database of the French reference centre for AIBD, we screened all the patients who were referred for an AIBD of the DEJ with a mucosal involvement, who neither met the diagnostic criteria for the diagnosis of BP, nor were typical of MMP. Sera were analysed by NC16A-ELISA and immunobloting against the C-terminal and LAD-1 parts of BP180. Skin biopsies were studied by direct immunoelectron microscopy (IEM).
RESULTS
Fifteen patients (4 males, 11 females) of mean age 70.8 ± 11.8 years were included. The mucosal involvement was localized in oral cavity in all cases and in pharyngeal/laryngeal or genital area in 8 (53%), and 6 patients (40%), respectively. No patient had ocular involvement, nor atrophic or fibrosing scars. All patients had extensive skin lesions (mean BPDAI score =65.9 ± 24.4), which predominated on the upper body part. Direct IEM performed on 8 patients showed IgG deposits on the lamina lucida in all cases, and the lamina densa in 5 cases. All sera recognized NC16A, while none recognized BP-230 in ELISA. 10 out of the 13 tested sera (76.9%) contained IgG which recognized the C-terminal domain of BP180 and 10 sera (76.9%) the LAD-1 domain of BP180. Patients poorly responded to super potent topical corticosteroids and were treated with oral corticosteroids ± immunosuppressant in 13 cases (86.6%).
CONCLUSION
This mixed muco-cutaneous pemphigoid differs from BP by the younger age of patients, multiple mucosae involvement, circulating antibodies against both the C- and N-terminal part of BP180, and very poor response to topical CS. It differs from MMP by extensive inflammatory skin lesions, absence of ocular involvement and atrophic/fibrosing scars.
Topics: Male; Female; Humans; Middle Aged; Aged; Aged, 80 and over; Pemphigoid, Bullous; Cicatrix; Non-Fibrillar Collagens; Skin; Immunoglobulin G
PubMed: 37006294
DOI: 10.3389/fimmu.2023.1134720 -
Annals of Gastroenterological Surgery Mar 2023The clinical features of postoperative primary tracheobronchial necrosis (P-TBN; the necrosis without anastomotic leakage or other cervical and mediastinal abscess)...
BACKGROUND
The clinical features of postoperative primary tracheobronchial necrosis (P-TBN; the necrosis without anastomotic leakage or other cervical and mediastinal abscess) remains unclear. This nationwide multicenter retrospective study first investigated the clinical features of P-TBN after esophagectomy for upper aerodigestive tract cancer with a large cohort.
METHODS
As a study of the Japan Broncho-Esophagological Society, a nationwide questionnaire survey was conducted in 67 institutions. The clinical data of 6370 patients who underwent esophagectomy for laryngeal, pharyngeal, and esophageal cancer between 2010 and 2019 were collected. Grades of P-TBN were defined as follows: Grade 1, mucosal necrosis; Grade 2, transmural bronchial wall necrosis without fistula or perforation; Grade 3, transmural bronchial wall necrosis with fistula or perforation.
RESULTS
P-TBN was observed in 48 (0.75%) of 6370 patients. The incidences of P-TBN for pharyngo-laryngo-cervical esophagectomy (PLCE; n = 1650), total pharyngo-laryngo-esophagectomy (TPLE; n = 205), and subtotal esophagectomy (SE; n = 4515) were 2.0%, 5.4%, and 0.1%, respectively. The upper mediastinal LN dissection ( = 0.016) and the higher level of the tracheal resection ( = 0.039) were significantly associated with a higher grade of necrosis in PLCE and TPLE. Overall survival rates were significantly lower in patients with Grade 2 ( = 0.009) and Grade 3 ( = 0.004) than in those with Grade 1.
CONCLUSION
The incidence of TBN restricted to P-TBN was lower than previously reported. Maintaining the tracheal blood flow is essential to prevent worsening P-TBN, especially in PLCE and TPLE. Our new P-TBN severity grade may predict the outcome of patients with P-TBN.
PubMed: 36998306
DOI: 10.1002/ags3.12625 -
Trends in Microbiology Aug 2023The nasopharynx is an important microbial reservoir for the emergence and spread of antibiotic-resistant organisms. The nasopharyngeal resistome is an extensive,... (Review)
Review
The nasopharynx is an important microbial reservoir for the emergence and spread of antibiotic-resistant organisms. The nasopharyngeal resistome is an extensive, adaptable reservoir of antibiotic-resistance genes (ARGs) within this niche. Metagenomic sequencing decodes the genetic material of all organisms within a sample using next-generation technologies, permitting unbiased discovery of novel ARGs and associated mobile genetic elements (MGEs). The challenges of sequencing a low-biomass bacterial sample have limited exploration of the nasopharyngeal resistome. Here, we explore the current understanding of the nasopharyngeal resistome, particularly the role of MGEs in propagating antimicrobial resistance (AMR), explore the advantages and limitations of metagenomic sequencing technologies and bioinformatic pipelines for nasopharyngeal resistome analysis, and highlight the key outstanding questions for future research.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Drug Resistance, Microbial; Genes, Bacterial; Nasopharynx; Metagenomics
PubMed: 36967247
DOI: 10.1016/j.tim.2023.02.008 -
Scientific Reports Mar 2023Since the discovery of olfactory receptor (OR) genes, their expression in non-olfactory tissues have been reported in rodents and humans. For example, mouse OR23 (mOR23)...
Since the discovery of olfactory receptor (OR) genes, their expression in non-olfactory tissues have been reported in rodents and humans. For example, mouse OR23 (mOR23) is expressed in sperm and muscle cells and has been proposed to play a role in chemotaxis and muscle migration, respectively. In addition, mouse mesencephalic dopaminergic neurons express various ORs, which respond to corresponding ligands. As the OR genes comprise the largest multigene family of G protein-coupled receptors in vertebrates (over 400 genes in human and 1000 in rodents), it has been difficult to categorize the extent of their diverse expression in non-olfactory tissues making it challenging to ascertain their function. The zebrafish genome contains significantly fewer OR genes at around 140 genes, and their expression pattern can be easily analyzed by carrying out whole mount in situ hybridization (ISH) assay in larvae. In this study, we found that 31 out of 36 OR genes, including or104-2, or108-1, or111-1, or125-4, or128-1, or128-5, 133-4, or133-7, or137-3 are expressed in various tissues, including the trunk, pharynx, pancreas and brain in the larvae. In addition, some OR genes are expressed in distinct brain regions such as the hypothalamus and the habenula in a dynamic temporal pattern between larvae, juvenile and adult zebrafish. We further confirmed that OR genes are expressed in non-olfactory tissues by RT-PCR in larvae and adults. These results indicate tight regulation of OR gene expression in the brain in a spatial and temporal manner and that the expression of OR genes in non-olfactory tissues are conserved in vertebrates. This study provides a framework to start investigating the function of ORs in the zebrafish brain.
Topics: Animals; Male; Mesencephalon; Olfactory Receptor Neurons; Receptors, Odorant; Semen; Spermatozoa; Zebrafish
PubMed: 36944644
DOI: 10.1038/s41598-023-30895-3 -
Ear, Nose, & Throat Journal Mar 2023Atypical Ramsay-Hunt syndrome is caused by varicella zoster viruses (VZV), without herpes, herpes is not around the ear, or posterior cranial nerve palsy is the first...
Atypical Ramsay-Hunt syndrome is caused by varicella zoster viruses (VZV), without herpes, herpes is not around the ear, or posterior cranial nerve palsy is the first clinical manifestation. In this case, a 60-year-old male patient with VZV invades the branches of the vagus nerve alone. The initial symptoms were in the pharynx and larynx, which presented as mucosal ulcers and voice disorders. The ear symptoms were only otalgia and auricular herpes, without deafness, tinnitus, or peripheral facial palsy. Herpes and ulcers healed with medication, but voice disorders caused by vocal cord paralysis did not return. Voice correction treatment has been implemented to help restore the movement and closure of the vocal cords, with ultimately good results. After voice correction treatment, the patient recovered without residual nerve palsy complications. Voice correction treatment has been shown to be potentially effective and promising in shortening the recovery period and improving the recovery rate for vocal cord paralysis caused by viral infection.
PubMed: 36927171
DOI: 10.1177/01455613231162222 -
Medicine Mar 2023The traditional methods for exchanging the endoscopic nasobiliary drainage (ENBD) tube from the mouth to the nose, such as the guidewire method, sponge holding forceps...
RATIONALE
The traditional methods for exchanging the endoscopic nasobiliary drainage (ENBD) tube from the mouth to the nose, such as the guidewire method, sponge holding forceps method, and finger method, have significant drawbacks including pharyngeal stimulation symptoms, high incidence of epistaxis, low success rate, and potential bite injuries to the operator.
PATIENT CONCERNS
A case series of 9 patients who underwent ENBD at Shenzhen Second People's Hospital from January 2021 to December 2021 was collected.
DIAGNOSES
The study included 9 patients diagnosed with choledocholithiasis, with 3 males and 6 females, with an average age of (55 ± 9.798) years (range 43-71).
INTERVENTIONS
The M-NED was used to exchange the ENBD tube, and the success rate, operation time, and complications were recorded.
OUTCOMES
All patients successfully completed the operation in one go with an average mouth-nose exchange time of (44.67 ± 13.388) seconds (range 28-65). Two patients had mild adverse events, one of which was controllable bleeding caused by nasal mucosal injury with an estimated blood loss of 1 mL. The other patient had nausea during the operation, which improved after completion.
LESSONS
The novel M-NED is an effective and safe method for exchanging the ENBD tube from the mouth to the nose with a high success rate and low incidence of complications. It is a device with potential clinical application value.
Topics: Male; Female; Humans; Adult; Middle Aged; Aged; Cholangiopancreatography, Endoscopic Retrograde; Catheterization; Nose; Choledocholithiasis; Drainage
PubMed: 36897720
DOI: 10.1097/MD.0000000000033215 -
Nature Mar 2023Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes. On infection, immune cells release...
Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes. On infection, immune cells release a 'storm' of cytokines and other mediators, many of which are detected by neurons; yet, the responding neural circuits and neuro-immune interaction mechanisms that evoke sickness behaviour during naturalistic infections remain unclear. Over-the-counter medications such as aspirin and ibuprofen are widely used to alleviate sickness and act by blocking prostaglandin E2 (PGE2) synthesis. A leading model is that PGE2 crosses the blood-brain barrier and directly engages hypothalamic neurons. Here, using genetic tools that broadly cover a peripheral sensory neuron atlas, we instead identified a small population of PGE2-detecting glossopharyngeal sensory neurons (petrosal GABRA1 neurons) that are essential for influenza-induced sickness behaviour in mice. Ablating petrosal GABRA1 neurons or targeted knockout of PGE2 receptor 3 (EP3) in these neurons eliminates influenza-induced decreases in food intake, water intake and mobility during early-stage infection and improves survival. Genetically guided anatomical mapping revealed that petrosal GABRA1 neurons project to mucosal regions of the nasopharynx with increased expression of cyclooxygenase-2 after infection, and also display a specific axonal targeting pattern in the brainstem. Together, these findings reveal a primary airway-to-brain sensory pathway that detects locally produced prostaglandins and mediates systemic sickness responses to respiratory virus infection.
Topics: Animals; Humans; Mice; Behavior, Animal; Blood-Brain Barrier; Brain; Brain Stem; Dinoprostone; Drinking; Eating; Influenza, Human; Movement; Nasopharynx; Orthomyxoviridae; Orthomyxoviridae Infections; Sensory Receptor Cells; Survival Rate
PubMed: 36890237
DOI: 10.1038/s41586-023-05796-0