-
Medicine Feb 2024Traditional observational and in vivo studies have suggested an etiological link between gastroesophageal reflux disease (GERD) and the development of extraesophageal...
Traditional observational and in vivo studies have suggested an etiological link between gastroesophageal reflux disease (GERD) and the development of extraesophageal diseases (EEDs), such as noncardiac chest pain. However, evidence demonstrating potential causal relationships is lacking. This study evaluated the potential causal relationship between GERD and EEDs, including throat and chest pain, asthma, bronchitis, chronic rhinitis, nasopharyngitis and pharyngitis, gingivitis and periodontal disease, cough, using multiple Mendelian randomization (MR) methods, and sensitivity analysis was performed. The Mendelian randomization Pleiotropy RESidual Sum and Outlier and PhenoScanner tools were used to further check for heterogeneous results and remove outliers. MR with inverse-variance weighted (IVW) showed a significant causal relationship between GERD and EEDs after Bonferroni correction. IVW results indicated that GERD increased the risk of chronic rhinitis, nasopharyngitis and pharyngitis (odds ratio [OR] = 1.482, 95% confidence interval [CI] = 1.267-1.734, P < .001], gingivitis and periodontal disease (OR = 1.166, 95% CI = 1.046-1.190, P = .001), throat and chest pain (OR = 1.585, 95% CI = 1.455-1.726, P < .001), asthma (OR = 1.539, 95% CI = 1.379-1.717, P < .001), and bronchitis (OR = 1.249, 95% CI = 1.168-1.335, P < .001). Sensitivity analysis did not detect pleiotropy. Leave-one-out analysis shows that MR results were not affected by individual single nucleotide polymorphisms. The funnel plot considers the genetic instrumental variables to be almost symmetrically distributed. This MR supports a causal relationship among GERD and EEDs. Precise moderation based on causality and active promotion of collaboration among multidisciplinary physicians ensure high-quality diagnostic and treatment recommendations and maximize patient benefit.
Topics: Humans; Nasopharyngitis; Mendelian Randomization Analysis; Gastroesophageal Reflux; Pharyngitis; Asthma; Bronchitis; Chest Pain; Gingivitis; Periodontal Diseases; Rhinitis; Genome-Wide Association Study
PubMed: 38363933
DOI: 10.1097/MD.0000000000037054 -
Phytomedicine : International Journal... Nov 2023Pudilan Xiaoyan Oral Liquid (PDL) is a famous traditional Chinese prescription recorded in the Chinese Pharmacopeia, which is widely used to treat inflammatory diseases...
Integrated metabolome-microbiome analysis investigates the different regulations of Pudilan Xiaoyan oral liquid in young rats with acute pharyngitis compared to adult rats.
BACKGROUND
Pudilan Xiaoyan Oral Liquid (PDL) is a famous traditional Chinese prescription recorded in the Chinese Pharmacopeia, which is widely used to treat inflammatory diseases of the respiratory tract in children and adults. However, the endogenous changes in children and adults with PDL in the treatment of acute pharyngitis remain unclear.
PURPOSE
The differential regulatory roles of PDL in endogenous metabolism and gut microbes in young and adult rats were investigated with a view to providing a preclinical data reference for PDL in medication for children.
METHODS
An acute pharyngitis model was established, and serum levels of inflammatory factors and histopathology were measured. This study simulated the growth and development of children in young rats and explored the endogenous metabolic characteristics and intestinal microbial composition after the intervention of PDL by using serum metabolomic technique and 16S rRNA high-throughput sequencing technique.
RESULTS
The results showed that PDL had therapeutic effects on young and adult rats with acute pharyngitis. Sixteen biomarkers were identified by metabolomics in the serum of young rats and 23 in adult rats. PDL can also affect intestinal microbial diversity and community richness in young and adult rats. Alloprevotella, Allobaculum, Alistipes, Bifidobacterium, and Enterorhabdus were prominent bacteria in young rats. Bacteria from the phylum Firmicutes of the adult rats changed more significantly under the treatment of PDL. In young rats, amino acid metabolism was the primary regulatory mode of PDL, whereas, in adult rats, glycerophospholipid metabolism was studied.
CONCLUSION
The regulation of PDL on the serum metabolite group and intestinal microflora in young rats was different from that in adult rats, indicating the necessity of an independent study on children's medication. PDL may also exert therapeutic effects on young and adult rats by regulating gut microbial homeostasis. The results support the clinical application of PDL.
Topics: Humans; Child; Rats; Animals; RNA, Ribosomal, 16S; Drugs, Chinese Herbal; Metabolome; Metabolomics; Gastrointestinal Microbiome; Pharyngitis
PubMed: 37611464
DOI: 10.1016/j.phymed.2023.155037 -
Journal of Clinical Medicine Sep 2023Acute pharyngitis can cause sore throat. This multicentre, active-controlled, randomised, open-label, and parallel-group study, conducted according to the German Medical...
Effectiveness and Tolerability of Ectoin Mouth and Throat Spray Althaea Honey (ERS09) for Sore Throat due to Acute Pharyngitis and Dry Cough: A Multicentre, Actively Controlled, Open Label Study in Germany.
Acute pharyngitis can cause sore throat. This multicentre, active-controlled, randomised, open-label, and parallel-group study, conducted according to the German Medical Devices Act, compared the effectiveness and tolerability of ERS09 mouth and throat spray with a well-established device for the treatment of sore throat caused by acute pharyngitis and dry cough. Patients were randomised 1:1 into ERS09/comparator groups (EMSER Sore Throat Spray) for 7 ± 2 days. Patients and investigators reported effectiveness (change in total symptom score [TSS]) and safety endpoints (incidence of adverse events [AEs]; adverse device effects [ADEs]). A total of 186 patients were included (ERS09: = 92; comparator: = 94). The baseline-adjusted mean TSS over 7 days was -90.14 and -74.91 in the ERS09 and comparator groups, respectively ( < 0.05). The majority of patients reached a 50% reduction in symptoms by day 6 (ERS09 = 78.85; comparator = 75.8%). Most patients reported a soothing effect within five minutes (ERS09 = 82%; comparator = 71%). Improvements in individual symptoms were similar with no significant differences between groups; more patients in the ERS09 group reported an improvement in pharyngeal redness/swelling. Three AEs unrelated to medication, one ADE following ERS09, and no serious AE/ADE were reported. ERS09 was as well tolerated and effective as the established device, showing greater improvement in the management of some symptoms and greater patient preference.
PubMed: 37762768
DOI: 10.3390/jcm12185813 -
International Journal of Infectious... Aug 2023Unnecessary and inappropriate antibiotic use is an increasing global health challenge. In limited resource settings, prophylactic antibiotics are still often used in... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Unnecessary and inappropriate antibiotic use is an increasing global health challenge. In limited resource settings, prophylactic antibiotics are still often used in (adeno)tonsillectomy (AT), despite evidence against their effectiveness. This study aimed to investigate the effect of prophylactic amoxicillin, given after AT in children.
METHODS
This is a secondary analysis from a two-center, double-blinded, randomized controlled, non-inferiority trial to study the effect of prophylactic amoxicillin on post-AT morbidity. Children aged 2-14 years with recurrent chronic tonsillitis and/or obstructive sleep apnea were randomly assigned to receive either placebo or amoxicillin for 5 days after the operation. Pre- and postoperative samples were collected for polymerase chain reaction (PCR) analyses to detect the five most important pathogens known to be common causes of tonsillitis. PCR results were compared before and after surgery as well as between placebo and amoxicillin.
RESULTS
PCR results were obtained, 109 in the amoxicillin group and 115 in the placebo group. In the amoxicillin group, 91% of patients had at least one positive PCR test before surgery and 87% after surgery. In the placebo group, the respective percentages were 92% and 90%. In both groups, a decrease in the total number of pathogens was found after surgery.
CONCLUSION
Prophylactic amoxicillin given after AT in children did not show a clinically relevant effect with respect to the number of oropharyngeal microorganisms as compared to placebo.
Topics: Humans; Child; Tonsillectomy; Amoxicillin; Palatine Tonsil; Tonsillitis; Anti-Bacterial Agents
PubMed: 37116578
DOI: 10.1016/j.ijid.2023.04.409 -
BMJ Global Health Oct 2023Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) encompasses the timely diagnosis and adequate treatment of the superficial group A... (Review)
Review
Research opportunities for the primary prevention and management of acute rheumatic fever and rheumatic heart disease: a National Heart, Lung, and Blood Institute workshop report.
Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) encompasses the timely diagnosis and adequate treatment of the superficial group A (GAS) infections pharyngitis and impetigo. GAS is the only known inciting agent in the pathophysiology of the disease. However, sufficient evidence indicates that the uptake and delivery of primary prevention approaches in RHD-endemic regions are significantly suboptimal. This report presents expert deliberations on priority research and implementation opportunities for primary prevention of ARF/RHD that were developed as part of a workshop convened by the US National Heart, Lung, and Blood Institute in November 2021. The opportunities identified by the Primary Prevention Working Group encompass epidemiological, laboratory, clinical, implementation and dissemination research domains and are anchored on five pillars including: (A) to gain a better understanding of superficial GAS infection epidemiology to guide programmes and policies; (B) to improve diagnosis of superficial GAS infections in RHD endemic settings; (C) to develop scalable and sustainable models for delivery of primary prevention; (D) to understand potential downstream effects of the scale-up of primary prevention and (E) to develop and conduct economic evaluations of primary prevention strategies in RHD endemic settings. In view of the multisectoral stakeholders in primary prevention strategies, we emphasise the need for community co-design and government engagement, especially in the implementation and dissemination research arena. We present these opportunities as a reference point for research organisations and sponsors who aim to contribute to the increasing momentum towards the global control and prevention of RHD.
Topics: Humans; National Heart, Lung, and Blood Institute (U.S.); Primary Prevention; Rheumatic Fever; Rheumatic Heart Disease; United States
PubMed: 37914184
DOI: 10.1136/bmjgh-2023-012356 -
Case Reports in Pediatrics 2023. Differentiating Crohn's disease (CD) and Behçet's disease (BD) with gastrointestinal (GI) manifestations can be clinically challenging, as current diagnostic criteria...
. Differentiating Crohn's disease (CD) and Behçet's disease (BD) with gastrointestinal (GI) manifestations can be clinically challenging, as current diagnostic criteria are not clear between both conditions and multiple symptoms could overlap. . The patient is an 8-year-old boy of Brazilian descent, who initially presented with a 1-year history of painful oral ulcers. Before presenting to the hospital, he had been treated for periodic fever, aphthous stomatitis, pharyngitis, and adenitis and placed on steroids, with relapsing symptoms on attempts to wean the doses. The initial workup was largely unremarkable. Buccal biopsies showed no granulomas, and the ophthalmologic exam was normal. Infectious and rheumatological tests were negative. Prometheus IBD sgi testing showed a pattern consistent with CD; however, the patient had multiple negative endoscopies, colonoscopies, and capsule endoscopies. He developed intermittent bloody stools and severe malnutrition and did not respond to infliximab, colchicine, or methotrexate. After a large GI bleed, a 4th colonoscopy was performed, which showed large round ulcers in the terminal ileum, and no granulomas. He was started on ustekinumab with clinical improvement. One month later, he developed bilateral hip effusion and meningismus, being diagnosed with aseptic meningitis secondary to COVID-19. He improved, but in one month developed worsening symptoms, and MRV showed extensive venous sinus thrombosis. The patient was started on enoxaparin, methylprednisolone, and colchicine, with resolution of the thrombus on a 3-month follow-up. The patient's overall symptoms remained controlled with clinical and biochemical remission on monthly ustekinumab. . Our patient had a challenging clinical course, with nonspecific systemic and intestinal manifestations which proved difficult to differentiate between BD and CD. Given endoscopic findings and the worsening of an auto-inflammatory reaction in the central nervous system after COVID-19 in a patient with controlled GI symptoms, the most likely diagnosis is BD.
PubMed: 37830113
DOI: 10.1155/2023/4705638 -
European Journal of Pediatrics Dec 2023Despite the advanced knowledge concerning autoinflammatory diseases (AID), more data regarding the optimal treatment options and outcomes of the children who met the...
Gray zone in the spectrum of autoinflammatory diseases: familial Mediterranean fever accompanying periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: single-center experience.
Despite the advanced knowledge concerning autoinflammatory diseases (AID), more data regarding the optimal treatment options and outcomes of the children who met the criteria of more than one AID are required. This study aimed to describe the demographic and clinical characteristics of children from familial Mediterranean fever (FMF)-endemic countries who meet both the FMF and the periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome criteria. Moreover, we aimed to measure the response rates to colchicine and tonsillectomy and evaluate the factors affecting the colchicine response in these patients. The study was conducted at pediatric rheumatology tertiary centre. A total of 131 patients (58 females; 73 males) who met both the modified Marshall and pediatric FMF criteria were included. The median age at onset was 18 months (1-77 months), and the mean age at diagnosis was 47 ± 21.88 months. The median interval between episodes was 21 (7-90) days. The median disease duration was 46 (6-128) months. Consanguineous marriage was detected in 17 (13%) of the patients. The most common clinical finding was fever (100%), followed by exudative pharyngitis (88.5%), abdominal pain (86.3%), arthralgia (61.8%), stomatitis (51.1%), adenitis (42%), myalgia (28.7%), chest pain (16%), maculopapular rash (12.2%), arthritis (8.4%), and erysipelas-like rash (4.6%). MEFV gene variants were identified in 106 (80.9%) patients. The most common variants were M694V heterozygous (29%). We found that patients with tonsillopharyngitis, aphthous stomatitis, and PFAPA family history were more likely to be colchicine-resistant and tonsillectomy responsive, while those with exon 10 MEFV gene mutations were more prone to have a favorable response to colchicine. Conclusion: PFAPA syndrome patients with exon 10 MEFV gene mutation, showing typical FMF symptoms, should be treated with colchicine, even after tonsillectomy. In multivariate analysis, PFAPA family history and lack of exon 10 MEFV gene mutations were independent risk factors for colchicine resistance. Thus, tonsillectomy may be recommended as a possible treatment option for these patients. It has yet to be clarified when colchicine treatment will be discontinued in patients whose attacks ceased after tonsillectomy that was performed due to colchicine unresponsiveness. What is Known: • A certain number of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome concomitantly fulfill the familial Mediterranean fever (FMF) criteria. • While colchicine is proposed as a first treatment choice in familial Mediterranean fever (FMF), corticosteroids are recommended as a first-line treatment in PFAPA syndrome patients. What is New: • In patients with concomitant PFAPA syndrome and FMF, PFAPA family history and lack of exon 10 MEFV gene mutation are predictive factors of colchicine resistance. • The presence of exon 10 MEFV gene mutations in patients with concomitant FMF and PFAPA syndrome has a favourable effect on response to colchicine treatment.
Topics: Male; Female; Child; Humans; Infant; Child, Preschool; Familial Mediterranean Fever; Stomatitis, Aphthous; Fever; Pharyngitis; Lymphadenitis; Colchicine; Lymphadenopathy; Tonsillectomy; Syndrome; Exanthema; Pyrin
PubMed: 37777601
DOI: 10.1007/s00431-023-05209-4 -
The Journal of Emergency Medicine Aug 2023
Topics: Humans; Mpox (monkeypox); Peritonsillar Abscess
PubMed: 37604603
DOI: 10.1016/j.jemermed.2023.04.029 -
International Journal of Hematology Oct 2023Eculizumab is a C5 inhibitor approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine...
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.
Topics: Humans; Atypical Hemolytic Uremic Syndrome; Hemoglobinuria, Paroxysmal; Japan; Influenza, Human; Nasopharyngitis; Complement Inactivating Agents; Myasthenia Gravis; Product Surveillance, Postmarketing; Pneumonia
PubMed: 37515657
DOI: 10.1007/s12185-023-03630-x -
RMD Open Nov 2023Different patient clusters were preliminarily suggested to dissect the clinical heterogeneity in Still's disease. Thus, we aimed at deriving and validating disease... (Observational Study)
Observational Study
BACKGROUND
Different patient clusters were preliminarily suggested to dissect the clinical heterogeneity in Still's disease. Thus, we aimed at deriving and validating disease clusters in a multicentre, observational, prospective study to stratify these patients.
METHODS
Patients included in GIRRCS AOSD-study group and AIDA Network Still Disease Registry were assessed if variables for cluster analysis were available (age, systemic score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and ferritin). K-means algorithm with Euclidean metric and Elbow plot were used to derive an adequate number of clusters.
RESULTS
K-means clustering assessment provided four clusters based on means standardised according to z-scores on 349 patients. All clusters mainly presented fever, skin rash and joint involvement. Cluster 1 was composed by 115 patients distinguished by lower values of age and characterised by skin rash myalgia, sore throat and splenomegaly. Cluster 2 included 128 patients identified by lower levels of ESR, ferritin and systemic score; multiorgan manifestations were less frequently observed. Cluster 3 comprised 31 patients categorised by higher levels of CRP and ferritin, they were characterised by fever and joint involvement. Cluster 4 contained 75 patients derived by higher values of age and systemic score. Myalgia, sore throat, liver involvement and life-threatening complications, leading to a high mortality rate, were observed in these patients.
CONCLUSIONS
Four patient clusters in Still's disease may be recognised by a multidimensional characterisation ('Juvenile/Transitional', 'Uncomplicated', 'Hyperferritinemic' and 'Catastrophic'). Of interest, cluster 4 was burdened by an increased rate of life-threatening complications and mortality, suggesting a more severe patient group.
Topics: Humans; Arthritis, Juvenile; C-Reactive Protein; Exanthema; Ferritins; Fever; Myalgia; Pharyngitis; Prospective Studies; Still's Disease, Adult-Onset
PubMed: 37989322
DOI: 10.1136/rmdopen-2023-003419