Application of narrow band imaging and Lugol's iodine staining in screening for nasopharyngeal carcinoma.

BACKGROUND: To investigate the diagnostic value of conventional white light endoscopy (WLE), narrow band imaging (NBI) endoscopy, and Lugol's iodine staining under WLE (endoscopic iodine staining) in the screening and early diagnosis of nasopharyngeal carcinoma. METHODS: Patients with nasopharyngeal lesions requiring biopsy attending the Department of Otolaryngology Head and Neck Surgery in our hospital between January 2021 and April 2023 were included in this study. Before biopsy, all subjects underwent conventional WLE, NBI endoscopy, and endoscopic iodine staining. On WLE, according to nasopharyngeal lesion morphology and color, patients were diagnosed with nasopharyngeal carcinoma ( +) or chronic hyperplastic nasopharyngitis (-). On NBI endoscopy, according to nasopharyngeal lesion vascular morphology, patients with type V manifestations (nasopharyngeal carcinoma) were categorized as NBI ( +) and patients with type I-IV manifestations (chronic hyperplastic nasopharyngitis) were categorized as NBI (-). Endoscopic iodine staining (1.6% Lugol's iodine solution) was positive ( +) if the mucosal surface was brown with no white patches, or negative (-) if there was no or light brown staining of the mucosal surface. Patients were divided into 2 groups based on histopathological diagnosis: nasopharyngeal carcinoma or chronic hyperplastic nasopharyngitis. Endoscopic diagnoses were compared with histopathological findings. The diagnostic performance of WLE, NBI endoscopy and endoscopic iodine staining for nasopharyngeal carcinoma were determined. RESULTS: This study included 159 patients. On histopathology, 29 patients were diagnosed with nasopharyngeal carcinoma, and 130 patients were diagnosed with chronic hyperplastic nasopharyngitis. There were no significant differences in the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic (ROC) curve (AUC) of conventional WLE, NBI endoscopy or endoscopic iodine staining for differentiating nasopharyngeal carcinoma and chronic hyperplastic nasopharyngitis. The diagnostic performance of the combination of conventional WLE, NBI endoscopy and endoscopic iodine staining was significantly improved compared to any procedure alone. CONCLUSIONS: Conventional WLE, NBI endoscopy or endoscopic iodine staining had good diagnostic performance for differentiating nasopharyngeal carcinoma and chronic hyperplastic nasopharyngitis. In particular, NBI endoscopy and endoscopic iodine staining alone or combined had clinical utility for identifying patients with nasopharyngeal lesions that are eligible for a watch-and-wait strategy.

Short-term risk and long-term incidence rate of infection and malignancy with IL-17 and IL-23 inhibitors in adult patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis.

The risk of infection and malignancy may be a concern for patients with psoriasis receiving interleukin (IL)-17 and IL-23 inhibitors, particularly with long-term treatments. We aimed to estimate the short-term risks and long-term incidence rates of infection and malignancy with IL-17 or IL-23 antagonists in adult patients with psoriasis and psoriatic arthritis through this comprehensive meta-analysis (PROSPERO registration number: CRD42022363127). We searched PubMed, MEDLINE, Web of Science and ClinicalTrials.gov until May 17, 2023 for randomized placebo-controlled trials and long-term (≥ 52 weeks) open-label extension studies. The estimates of short-term risk ratios (RRs) and long-term exposure-adjusted incidence rates (EAIRs) were pooled using R software 4.1.1 and STATA 16.0. This review included 45 randomized placebo-controlled studies and 27 open-label extension studies. Short-term RRs of serious infection, overall infection and malignancy were 1.45 (95% confidence intervals, 95% CI: 0.81-2.59), 1.20 (95% CI: 1.06-1.35), 0.83 (95% CI: 0.41-1.71) with IL-17 inhibitors; and 0.68 (95% CI: 0.38-1.22), 1.13 (95% CI: 1.00-1.28), 0.87 (95% CI: 0.37-2.04) with IL-23 inhibitors. Increased short-term risks of nasopharyngitis and Candida infection with IL-17 inhibitors were found. Long-term EAIRs of serious infection, overall infection, nonmelanoma skin cancer (NMSC), malignancies excluding NMSC, nasopharyngitis and upper respiratory tract infection were 1.11/100 patient-years (PYs), 57.78/100PYs, 0.47/100PYs, 0.24/100PYs, 15.07/100PYs, 8.52/100PYs, 3.41/100PYs with IL-17 inhibitors; and 1.09/100PYs, 48.50/100PYs, 0.40/100PYs, 0.43/100PYs, 10.75/100PYs, 5.84/100PYs with IL-23 inhibitors. Long-term EAIR of Candida infection was 3.41/100PYs with IL-17 inhibitors. No active or reactivated tuberculosis was ever reported in all the trials, and only a few cases of latent tuberculosis, hepatitis, and herpes zoster were reported during the long-term extension periods. No evidence of increased EAIRs of infection and malignancy with longer durations was found. Our study suggested that short-term risk and long-term incidence of infections and malignancies in psoriasis patients receiving IL-17 inhibitors and IL-23 inhibitors are generally low. However, close monitoring is required for nasopharyngitis and Candida infection with IL-17 inhibitors. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363127.

Randomized controlled trial of KW-6356 monotherapy in patients with early untreated Parkinson's disease.

INTRODUCTION: KW-6356 is a novel selective adenosine A2A receptor antagonist/inverse agonist. We evaluated the efficacy and safety of KW-6356 as monotherapy in patients with early, untreated Parkinson's disease (PD). METHODS: This was a randomized, placebo-controlled, double-blind study conducted in Japan to investigate the efficacy and safety of once-daily KW-6356 (3 or 6 mg/day) orally administered as monotherapy for 12 weeks in patients with early PD (NCT02939391). The primary endpoint was the least squares means of change from baseline in the MDS-UPDRS Part III total score. RESULTS: Overall, 168 patients were randomized and treated (KW-6356 3 mg/day n = 55; 6 mg/day n = 58, placebo n = 55); Week 12 completion rates were >90% per group. LS mean [95% CI] changes from baseline to Week 12 in MDS-UPDRS Part III total scores were -5.37 [-7.25, -3.48] for 3 mg/day, -4.76 [-6.55, -2.96] for 6 mg/day and -3.14 [-4.97, -1.30] for placebo. Changes from baseline were larger for both KW-6356 groups than for the placebo group at all time points. Secondary endpoints supported the primary findings with larger changes in MDS-UPDRS Part II, Parts II + III, and Total scores in the KW-6356 groups than in the placebo group. Treatment was well-tolerated; the most common treatment-emergent adverse events with KW-6356 were constipation (n = 4 [7.3%] and n = 6 [10.3%] in the 3 and 6 mg/day groups, respectively) followed by nasopharyngitis (n = 4 [7.3%] and n = 5 [8.6%] in the 3 and 6 mg/day groups, respectively). CONCLUSION: KW-6356 monotherapy is well tolerated and more effective than placebo in patients with early, untreated PD.

Successful management of nasopharyngitis caused by Schizophyllum commune in a captive cheetah (Acinonyx jubatus).

Herein, we describe the management of nasopharyngitis caused by Schizophyllum commune infection in a captive cheetah. Computed tomography revealed a nodule in the nasal cavity and pharynx, and an endoscopic biopsy was performed. As a result, the nodule was surgically resected because of a suspected carcinoma. However, the surgical specimen was histologically re-evaluated and a fungal granuloma was diagnosed. Sequence analysis of DNA from formalin-fixed, paraffin-embedded samples revealed S. commune infection. The cheetah was administered fluconazole orally for 73 days. However, the drug was ineffective and itraconazole was administered for 14 days. Symptoms such as nasal discharge and sneezing have completely resolved for 4 years.

Real-world safety profile of eculizumab in patients with paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, or generalized myasthenia gravis: an integrated analysis of post-marketing surveillance in Japan.

Eculizumab is a C5 inhibitor approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR + gMG) in Japan. We report integrated safety data from post-marketing surveillance in these three indications, focusing on commonly occurring adverse events (AEs) and infection-related AEs. Of 1219 patients registered, 1055 (PNH: 780; aHUS: 192; AChR + gMG: 83) had available safety data. Total eculizumab exposure was 3977.361 patient-years. AEs were reported in 74.03% of patients. AEs with an incidence of  ≥ 1.0 per 100 patient-years included hemolysis, headache, nasopharyngitis, renal impairment, anemia, pneumonia, upper respiratory tract inflammation, influenza, condition aggravated, and infection. The incidence of infection-related AEs was 21.30 per 100 patient-years, the most frequent types (≥ 1.0 per 100 patient-years) being nasopharyngitis, pneumonia, influenza, and infection. Meningococcal infections were reported in four patients (0.10 per 100 patient-years). Two patients died from meningococcal sepsis, with a mortality rate of 0.05 per 100 patient-years. This is the largest safety dataset on eculizumab in Japan derived from more than 10 years of clinical experience. No new safety signals were observed and the safety profile of eculizumab was consistent with that in previous clinical trials and international real-world safety analyses.

[Efficacy of bioregulative drugs in the treatment of otitis media with effusion associated with rhinosinusitis and adenoiditis]. / Effektivnost' preparatov bioregulyatsionnoi meditsiny pri lechenii ekssudativnogo srednego otita, sopryazhennogo s rinosinusitom i adenoiditom.

PURPOSE: Improving of otitis media with effusion (OME) with rhinosinusitis (RS) and adenoiditis treatment effectiveness. MATERIALS AND METHODS: The study included 112 patients 12-18 y.o. with otitis media with effusion, who were divided into 2 groups depending on the treatment scheme. The Group I (the main group) patients treatment included Traumeel S and Euphorbium compositum Nasentropfen S in addition to the standard treatment, and the Group II (comparison), children were prescribed standard therapy. Patients of both groups were divided into 3 subgroups depending on the upper respiratory tract inflammation symptoms: A - patients with adenoiditis; B - with rhinosinusitis and C - combination of adenoiditis and rhinosinusitis. The comparison group (groups IIB and IIC) treatment scheme (children with rhinosinusitis) included topical corticosteroids and the main group patients didn't receive corticosteroids. All patients went through complaints and anamnesis collection, routine otorhinolaryngological and instrumental examination before and after treatment. RESULTS: Analysis of treatment results demonstrated high efficacy of multicomponent drugs with low doses of active ingredients in the therapy of patients with OME, regardless of comorbid pathology. Significantly better results were obtained in the patients treated with bioregulatory drugs when comparing the outcomes of OME therapy in combination with adenoiditis (groups IA and IIA). Comparable efficacy results were obtained in the treatment group of patients with OME associated with RS (in groups IB and IIB as well as in groups IC and IIC), where GCS was received in the comparison group. The high efficacy and safety of bioregulatory drugs makes the use of these agents a promising treatment for patients with OME, RS and adenoiditis.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome and Syndrome of Unexplained Recurrent Fevers in Children and Adults.

Children and adults with autoinflammatory disorders, who often experience recurrent fevers, rashes, cold-induced symptoms, conjunctivitis, lymphadenopathy, recurrent infections, aphthous stomatitis, and abnormal blood cell counts, may present to the allergist/immunologist because the symptoms mimic allergies and disorders of immunity. In recent years, there has been increased recognition of non-monogenic autoinflammatory disorders, including periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome and syndrome of undifferentiated recurrent fevers. For many clinical practitioners, the natural history, diagnostic criteria, differential diagnoses, and preferred therapies remain challenging because of the presumed rarity of patients and the evolving field of autoinflammation. Here, we aim to provide a practical framework for the clinical allergist/immunologist to evaluate and treat this patient population.

AURKA, as a potential prognostic biomarker, regulates autophagy and immune infiltration in nasopharyngeal carcinoma.

BACKGROUND: Dysfunction of Aurora A (AURKA) plays crucial role in tumorigenesis and development of many types of cancer. However, the role of AURKA in nasopharyngeal carcinoma (NPC) has not been investigated yet. MATERIALS AND METHODS: Two independent NPC cohorts (GSE61218 and GSE102349) were enrolled from public database to investigate the expression level of AURKA between NPC and nasopharyngitis samples, the association of AURKA expression level with prognosis in NPC, and the potential mechanism of AURKA in NPC by using bioinformatics analyses. The expression level of AURKA protein in 62 paired NPC and nasopharyngitis tissues was evaluated by immunohistochemistry (IHC). Two NPC cell lines (SUNE-1 and CNE-2) were enrolled and the expression levels of AURKA in the NPC cells were inhibited by RNA interference. The expression levels of mRNAs were tested by qPCR and western-blotting. CCK-8 assay was applied to measure the cell growth. Cell migration was measured by using wound healing assays. RESULTS: AURKA was highly expressed in NPC samples compared to nasopharyngitis samples in GSE61218, which was confirmed by IHC. High expression of AURKA was associated with worse prognosis in GSE102349. Notably, silencing of AURKA was associated with significantly decreased cell growth and migration in NPC. Moreover, we found that the differentially expressed genes between high and low AURKA expression groups in GSE102349 were majorly enriched in both autophagy-related and immune-related pathways. Additionally, the expression level of AURKA was associated with the expression levels of autophagy-related genes and the infiltration of immune cells. CONCLUSION: AURKA overexpressed in NPC, which was associated with poor prognosis. Silencing of AURKA inhibited the proliferation and migration of NPC cells. Besides, AURKA might participate in the regulation of both autophagy and immunity in NPC.

Laryngopharyngeal reflux induced sleep-related laryngospasm.

BACKGROUND: Sleep-related laryngospasm (SRL) has been defined as the sustained closure of the vocal cords during sleep. Studies have suggested that it is a rare manifestation of laryngopharyngeal reflux (LPR). Difficulties in diagnosing SRL and LPR have led to the condition being under-recognised in the clinical setting. AIMS: The aim of this study was to determine if LPR was the cause of the SRL symptoms seen in our patients. METHODS: A retrospective chart assessment of patients with SRL. Patients with risk factors for LPR were identified. These included smoking status, alcohol intake, a history of dyspepsia or history of gastroesophageal reflux disease, a history of late-night eating and a history of eating spicy or fatty foods before bed. A clinical diagnosis based on the history and response to management was made for the diagnosis of LPR. All were advised to refrain from late meals and those with signs of nasopharyngitis were commenced on proton pump inhibitor therapy. RESULTS: Nineteen patients (mean age ± SD: 57.21 ± 15.18) were included in the study. All had at least one risk factor for LPR. Ten (52.6%) had signs of nasopharyngitis on nasendoscopy. Following treatment, 17 (89.5%) reported no further SRL symptoms at 1-year follow-up. CONCLUSION: SRL is a largely unknown and under-diagnosed condition. We believe this study provides supportive evidence for the causal relationship between LPR and SRL.

[The effectiveness comparison of various conservative treatment options of nasopharyngeal inflammation in children]. / Sravnenie effektivnosti razlichnykh variantov konservativnogo lecheniya vospaleniya glotochnoi mindaliny u detei.

The problem of hyperplasia/inflammation of the structures of the Pirogov-Waldeyer lymphoid-pharyngeal ring and related complications is one of the most frequently discussed in pediatric practice, in particular in matters of methods and expediency of conservative treatment. The article describes the effectiveness of various regiment of conservative treatment of pediatric patients with inflammation of the pharyngeal tonsil (adenoiditis) based on the results of an open comparative observational study. OBJECTIVE: To compare the effectiveness of various schemes of conservative therapy of adenoiditis in children. MATERIAL AND METHODS: 154 patients were divided into three groups: group I - standard therapy; group II - standard therapy + a specially developed homeopathic protocol; group III - a specially developed homeopathic protocol. At each of the visits (day 0th, 7th, 30th, and 90th), ENT-organs endoscopy and a 10-point visual assessment of symptoms were performed by analog score. The effectiveness of treatment (day 7th, 30th, and 90th) was evaluated by both doctors and patients. RESULTS: Analysis of the results showed that the symptoms of adenoiditis were stopped most quickly (day 7th) in patients of group I, but more pronounced and prolonged positive dynamics was noted in comparison groups II and III (only in these groups parents/legal representatives of patients rated the effectiveness as recovery in 25% and 35%, respectively). CONCLUSION: Conservative treatment of adenoiditis: has a positive effect (the severity and duration depends on the therapy regimen); avoids adenotomy, especially in patients who have taken homeopathic medications as a part of combined therapy. The use of a standardized homeopathic protocol is possible, both in combination with the use of other medications, and as monotherapy. Against the background of taking homeopathic medications, undesirable side effects may occur, which the parents of patients should be informed about in advance.

The use of SN-5 to differentiate chronic rhinosinusitis and chronic adenoiditis in children.

BACKGROUND: Chronic adenoiditis (CA) and chronic rhinosinusitis (CRS) present with similar symptoms, but an accurate diagnosis is critical for optimal treatment. We aim to differentiate CRS and CA based on sinonasal symptoms using the Sinus and Nasal Quality of Life Survey (SN-5) in children. METHODS: This is a retrospective cohort study. Children (age 12 and younger) presenting with chronic sinonasal symptoms were divided into 2 groups based on CT scan sinus findings: CA group included patients with CT Lund-Mackay (LM) score <5 and CRS group included patients with CT LM score of 5 and more. SN-5 scores for each group were then compared, and both groups were compared to a control group. Other demographic data were also collected and analyzed. RESULTS: There were 27 patients in the CA group, 42 patients in CRS group and 38 patients in the control group. Mean SN-5 scores were 2.03±0.71 for the control group, 3.49±1.00 for the CA group, and 4.53±0.77 for the CRS group (p < 0.0001); Statistical significance persisted when CA and CRS were compared in subset analysis (p < 0.0001). CT LM score was 2.70±2.07 for the CA group and 9.94±3.46 for the CRS group (p < 0.0001). Rates of asthma, allergic rhinitis, and smoke exposure differed between the three groups (p < 0.01), but they were not statistically different when CA and CRS were compared in subset analysis. CONCLUSION: Children with CRS have higher SN-5 score than children with CA. SN-5 score can be used to help otolaryngologists differentiate between these two clinical entities.

Infection risk in psoriatic patients receiving tumour necrosis factor inhibitors: a 20-year systematic review and meta-analysis of randomized controlled trials.

Tumour necrosis factor inhibitors (TNFis) are commonly used for treating psoriatic diseases; however, the risk of infection while receiving TNFis remains uncertain. The aim of this study was to investigate the infection risk in patients with psoriatic disease receiving TNFis. A prospectively registered systematic literature search was conducted in Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ClinicalTrials.gov databases from inception to December 31, 2021. We included double-blind randomized controlled trials that compared TNFis or other biologics with placebo in adults with psoriasis or psoriatic arthritis. The primary outcomes included overall and serious infection risks, and secondary outcomes included upper respiratory infections and nasopharyngitis risks. The risk ratio of the dichotomous outcome was calculated using the Mantel-Haenszel method with random effects, and heterogeneity was assessed using Cochran's Q statistic and quantified using the I-squared statistic. A total of 48 studies with 15 464 patients with psoriatic diseases were included. The meta-analysis demonstrated a slightly increased overall infection risk (risk ratio = 1.09; 95% confidence interval, 1.02-1.15) but not serious infection risk (risk ratio = 0.95; 95% confidence interval, 0.61-1.49) among patients receiving TNFis. There were also no increased risks of upper respiratory infections (risk ratio = 1.10; 95% confidence interval, 0.94-1.28) or nasopharyngitis (risk ratio = 1.14; 95% confidence interval, 1.00-1.30). In subgroup analyses using the fixed effects model, only etanercept and certolizumab pegol were, respectively, associated with an increased risk of overall infection (RR = 1.14, 95% CI, 1.03-1.27) and upper respiratory infections (RR = 1.42, 95% CI, 1.02-1.98). In conclusion, evidence to date suggests an increased overall infection risk that is generally tolerable in patients with psoriatic diseases receiving TNFis. There are no increased risks of serious infections, upper respiratory infections or nasopharyngitis.

Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials.

BACKGROUND: There is a great unmet need for advanced therapies that provide rapid, robust, and sustained disease control for patients with ulcerative colitis. We assessed the efficacy and safety of upadacitinib, an oral selective Janus kinase 1 inhibitor, as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. METHODS: This phase 3, multicentre, randomised, double-blind, placebo-controlled clinical programme consisted of two replicate induction studies (U-ACHIEVE induction [UC1] and U-ACCOMPLISH [UC2]) and a single maintenance study (U-ACHIEVE maintenance [UC3]). The studies were conducted across Europe, North and South America, Australasia, Africa, and the Asia-Pacific region at 199 clinical centres in 39 countries (UC1), 204 clinical centres in 40 countries (UC2), and 195 clinical centres in 35 countries (UC3). Patients aged 16-75 years with moderately to severely active ulcerative colitis (Adapted Mayo score 5-9; endoscopic subscore 2 or 3) for at least 90 days were randomly assigned (2:1) to oral upadacitinib 45 mg once daily or placebo for 8 weeks (induction studies). Patients who achieved clinical response following 8-week upadacitinib induction were re-randomly assigned (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks (maintenance study). All patients were randomly assigned using web-based interactive response technology. The primary endpoints were clinical remission per Adapted Mayo score at week 8 (induction) and week 52 (maintenance). The efficacy analyses in the two induction studies were based on the intent-to-treat population, which included all randomised patients who received at least one dose of treatment. In the maintenance study, the primary efficacy analyses reported in this manuscript were based on the first 450 (planned) clinical responders to 8-week induction therapy with upadacitinib 45 mg once daily. The safety analysis population in the induction studies consisted of all randomised patients who received at least one dose of treatment; in the maintenance study, this population included all patients who received at least one dose of treatment as part of the primary analysis population. These studies are registered at ClinicalTrials.gov, NCT02819635 (U-ACHIEVE) and NCT03653026 (U-ACCOMPLISH). FINDINGS: Between Oct 23, 2018, and Sept 7, 2020, 474 patients were randomly assigned to upadacitinib 45 mg once daily (n=319) or placebo (n=155) in UC1. Between Dec 6, 2018, and Jan 14, 2021, 522 patients were randomly assigned to upadacitinib 45 mg once daily (n=345) or placebo (n=177) in UC2. In UC3, a total of 451 patients (21 from the phase 2b study, 278 from UC1, and 152 from UC2) who achieved a clinical response after 8 weeks of upadacitinib induction treatment were randomly assigned again to upadacitinib 15 mg (n=148), upadacitinib 30 mg (n=154), and placebo (n=149) in the primary analysis population. Statistically significantly more patients achieved clinical remission with upadacitinib 45 mg (83 [26%] of 319 patients in UC1 and 114 [34%] of 341 patients in UC2) than in the placebo group (seven [5%] of 154 patients in UC1 and seven [4%] of 174 patients; p<0·0001; adjusted treatment difference 21·6% [95% CI 15·8-27·4] for UC1 and 29·0% [23·2-34·7] for UC2). In the maintenance study, clinical remission was achieved by statistically significantly more patients receiving upadacitinib (15 mg 63 [42%] of 148; 30 mg 80 [52%] of 154) than those receiving placebo (18 [12%] of 149; p<0·0001; adjusted treatment difference 30·7% [21·7-39·8] for upadacitinib 15 mg vs placebo and 39·0% [29·7-48·2] for upadacitinib 30 mg vs placebo). The most commonly reported adverse events in UC1 were nasopharyngitis (15 [5%] of 319 in the upadacitinib 45 mg group vs six [4%] of 155 in the placebo group), creatine phosphokinase elevation (15 [4%] vs three [2%]), and acne (15 [5%] vs one [1%]). In UC2, the most frequently reported adverse event was acne (24 [7%] of 344 in the upadacitinib 45 mg group vs three [2%] of 177 in the placebo group). In both induction studies, serious adverse events and adverse events leading to discontinuation of treatment were less frequent in the upadacitinib 45 mg group than in the placebo group (serious adverse events eight [3%] vs nine (6%) in UC1 and 11 [3%] vs eight [5%] in UC2; adverse events leading to discontinuation six [2%] vs 14 [9%] in UC1 and six [2%] vs nine [5%] in UC2). In UC3, the most frequently reported adverse events (≥5%) were worsening of ulcerative colitis (19 [13%] of 148 in the upadacitinib 15 mg group vs 11 [7%] of 154 in the upadacitinib 30 mg group vs 45 [30%] of 149 in the placebo group), nasopharyngitis (18 [12%] vs 22 [14%] vs 15 [10%]), creatine phosphokinase elevation (nine [6%] vs 13 [8%] vs three [2%]), arthralgia (nine [6%] vs five [3%] vs 15 [10%]), and upper respiratory tract infection (seven [5%] vs nine [6%] vs six [4%]). The proportion of serious adverse events (ten [7%] vs nine [6%] vs 19 [13%]) and adverse events leading to discontinuation (six [4%] vs ten [6%] vs 17 [11%]) was lower in both upadacitinib groups than in the placebo group. Events of cancer, adjudicated major adverse cardiac events, or venous thromboembolism were reported infrequently. There were no treatment-related deaths. INTERPRETATION: Upadacitinib demonstrated a positive efficacy and safety profile and could be an effective treatment option for patients with moderately to severely active ulcerative colitis. FUNDING: AbbVie.

Risk of infections of biological and targeted drugs in patients with spondyloarthritis: meta-analysis of randomized clinical trials.

BACKGROUND: Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool. RESULTS: In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07-1.26, P < 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26-2.17, P < 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04-1.32, P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10-1.42, P < 0.001), and Candida infection (Peto OR: 2.64, 95% CI: 1.48-4.71, P  = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-a inhibitors (Peto OR: 1.38, 95% CI: 1.13-1.68, P  = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08-2.22, P  = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14-1.69, P  = 0.001); higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26-9.55, P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38-2.91, P < 0.001); higher risk of URTI for TNF-a inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05-1.78, P = 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08-2.36, P = 0.018); higher risk of nasopharyngitis for TNF-a inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05-1.90, P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09-2.05, P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01-1.82, P = 0.044); higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03-4.62, P = 0.043); higher risk of Candida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31-4.84, P = 0.006). CONCLUSIONS: This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, and Candida infection, which should be paid attention to in our clinical practice.

Infectious events in patients treated with immune checkpoint inhibitors, chimeric antigen receptor T cells, and bispecific T-cell engagers: a review of registration studies.

BACKGROUND: Immunological treatments (immune checkpoint inhibitors [ICIs], chimeric antigen receptor T [CAR-T] cells, bispecific T-cell engagers [BiTEs]) have deeply changed the treatment of several cancers. However, the impact of these treatments on the risk of developing infections has not been completely ascertained yet. METHODS: We reviewed all the registration studies of currently approved ICIs, CAR-T cells, and BiTEs to collect all the reported infections. For each drug, we have generated a report with the infections occurring in at least 10% of the patients enrolled. RESULTS: The most frequently reported infections involving patients treated with ICIs involved the respiratory tract, including nasopharyngitis, upper respiratory tract infections, and pneumonia and the urinary tract. Those treated with CAR-T cells frequently reported the incidence of unspecified infections and infestations, bacterial infections, and viral infections. In patients treated with BiTEs, nasopharyngitis, pneumonia, and device-related infections were the most frequently reported conditions. CONCLUSIONS: A wide range of infections are reported in registration studies and clinical trials of ICIs, CAR-T cells, and BiTEs.

[Hypertrophy of adenoid vegetation in modern treatment conditions]. / Problema gipertrofii adenoidnykh vegetatsii v usloviyakh sovremennoi terapii.

We present data on the hypertrophy of adenoid vegetation in modern treatment conditions. Actual aspects of the etiology of hypertrophy of adenoid vegetation and chronic adenoiditis are discussed, and mechanisms of the formation of local immunity and the effect of immunomodulating therapy are also described. Data on the morphology of adenoids, immunity condition after exposure to modern drugs and the rationality of treatment in frequently ill children are presented.

Acute Herpetic Nasopharyngitis in an Adult Patient: A Case Report and Literature Review.

OBJECTIVE: To report a case of herpes virus-associated nasopharyngitis in an adult patient. METHODS: The patient's medical record was reviewed for demographic and clinical data. For literature review, all case reports or other publications published in English literature were identified using Pubmed with the MeSH terms "herpes," "nasopharyngitis," and "upper respiratory infection." RESULTS: A 40-year-old male presented for nasal congestion and a suspected nasal mass. Computed tomography of the sinuses revealed edematous changes in the nasopharynx which exerted a downward mass effect at the right aspect of the soft palate. Flexible fiberoptic laryngoscopy (FFL) revealed a lesion arising from the posterior aspect of the soft palate with extension into the posterior nasal cavity as well as copious mucopurulent secretions consistent with a superimposed acute sinusitis. Rigid nasal endoscopy demonstrated a friable and ulcerated lesion arising from the aforementioned anatomical location. Biopsy of this lesion and subsequent immunohistochemical analysis revealed a diagnosis of herpetic nasopharyngitis. CONCLUSIONS: Herpetic infection should be in the differential diagnosis of patients presenting with atypical symptoms of nasopharyngitis. Early accurate diagnosis and appropriate specific management can limit the duration of disease course and prevent further complications.

[Microbiocenosis-regulating therapy of inflammatory pathology of the oropharynx]. / Mikrobiotsenoz-reguliruyushchaya terapiya vospalitel'noi patologii rotoglotki.

Inflammatory pathology of the oropharynx, which does not lose its relevance, is a problem that is of interest to doctors of various specialties. As one of the main causes of inflammatory diseases of the pharynx, the influence of microorganisms, primarily viruses, on the mucous membrane of the upper respiratory tract is indicated. The authors of the article emphasize the importance of preserving the indigenous microbiota, which provides a barrier function and prevents the adhesion and colonization of pathogenic microorganisms. In this regard, the most effective and safe is local microbiocenosis-regulatory therapy using lysozyme, a natural peptide that has antiseptic, anti-inflammatory and immunoregulatory effects. As such a drug, the authors recommend the combined drug Lorolizin, which can be used in the treatment of acute pharyngitis, acute tonsillitis, and adenoiditis.

A first case report of nasopharyngeal Mycobacterium abscessus subspecies massiliense infection.

BACKGROUND: Mycobacterium abscessus subspecies massiliense is a non-tuberculous mycobacteriosis and was subdivided from Mycobacterium abscessus in 2006. This article is the first report on nasopharyngitis caused by Mycobacterium abscessus subspecies massiliense. CASE PRESENTATION: A 45-year-old woman had an 18-month history of recurrent nasopharyngitis and presented with pain in the throat. Mycobacterial tissue culture and polymerase chain reaction testing revealed the presence of Mycobacterium abscessus subspecies massiliense in the nasopharyngeal tissue. This patient underwent surgery, followed by multiple rounds of chemotherapy with oral and intravenous antibiotic agents for 16 weeks. She has had no recurrence during the 56 weeks since treatment. CONCLUSION: It is difficult to detect the presence of Mycobacterium abscessus subspecies massiliense in a culture from the swabbing sample. The tissue culture from a biopsy specimen is mandatory for the identification of the species. Currently, no definite treatment policy is available and only empirical treatment is applied. This case is an important for the diagnosis and treatment of this bacterial infection on nasopharynx.

Chronic adenoiditis.

In addition to acute adenoiditis and adenoid hypertrophy/vegetation, chronic adenoiditis is another disease of the adenoids. However, most physicians overlook chronic adenoiditis or confuse it with adenoid hypertrophy/vegetation. The incidence of chronic adenoiditis has increased in recent years as a result of higher rates of chronic nasopharyngeal or upper airway infections. The clinical characteristics of chronic adenoiditis can include but are not restricted to the following: long-term infection (especially bacterial infection); obstruction of the upper airway; infections of adjacent regions, such as the nose, nasal sinus, pharyngeal space, middle ear, and atlantoaxial joint; induced upper airway cough syndrome; and the presence of several "infectious-immune" diseases, including rheumatic fever, autoimmune nephropathy, and anaphylactoid purpura. To date, no consensus on the treatment of chronic adenoiditis is available. However, adenoidectomy can address the local obstruction, and some patients benefit from systemic or local anti-bacterial therapy. Physicians in the Departments of Otolaryngology, Respiration, and Pediatrics should be familiar with the clinical manifestations of chronic adenoiditis and try to develop effective treatment methods for this disease.