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Proceedings of the National Academy of... Mar 2024Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the...
Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTS). These NTS neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTS→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.
Topics: Humans; Animals; Mice; Pharynx; Anxiety; Pharyngitis; Brain; Sensory Receptor Cells; Inflammation
PubMed: 38446848
DOI: 10.1073/pnas.2312136121 -
JAMA May 2024
Topics: Humans; Anti-Bacterial Agents; Pharyngitis; Streptococcal Infections; Streptococcus pyogenes; Penicillins
PubMed: 38696184
DOI: 10.1001/jama.2024.3326 -
Frontiers in Endocrinology 2023The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain... (Comparative Study)
Comparative Study Meta-Analysis
Comparative safety of different recommended doses of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.
OBJECTIVE
The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain uncertain. This study aims to comprehensively estimate and rank the relative safety outcomes with different doses of SGLT-2i for T2DM.
METHODS
PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to 31 May 2023. We included double-blind randomized controlled trials (RCTs) comparing SGLT-2i with placebo or another antihyperglycemic as oral monotherapy in the adults with a diagnosis of T2DM.
RESULTS
Twenty-five RCTs with 12,990 patients randomly assigned to 10 pharmacological interventions and placebo were included. Regarding genital infections (GI), all SGLT-2i, except for ertugliflozin and ipragliflozin, were associated with a higher risk of GI compared to placebo. Empagliflozin 10mg/d (88.2%, odds ratio [OR] 7.90, 95% credible interval [CrI] 3.39 to 22.08) may be the riskiest, followed by empagliflozin 25mg/d (83.4%, OR 7.22, 95%CrI 3.11 to 20.04)) and canagliflozin 300mg/d (70.8%, OR 5.33, 95%CrI 2.25 to 13.83) based on probability rankings. Additionally, dapagliflozin 10mg/d ranked highest for urinary tract infections (UTI, OR 2.11, 95%CrI 1.20 to 3.79, 87.2%), renal impairment (80.7%), and nasopharyngitis (81.6%) when compared to placebo and other treatments. No increased risk of harm was observed with different doses of SGLT-2i regarding hypoglycemia, acute kidney injury, diabetic ketoacidosis, or fracture. Further subgroup analysis by gender revealed no significantly increased risk of UTI. Dapagliflozin 10mg/d (91.9%) and canagliflozin 300mg/d (88.8%) ranked first in the female and male subgroups, respectively, according to the probability rankings for GI.
CONCLUSION
Current evidence indicated that SGLT-2i did not significantly increase the risk of harm when comparing different doses, except for dapagliflozin 10mg/d, which showed an increased risk of UTI and may be associated with a higher risk of renal impairment and nasopharyngitis. Additionally, compared with placebo and metformin, the risk of GI was notably elevated for empagliflozin 10mg/d, canagliflozin 300mg/d, and dapagliflozin 10mg/d. However, it is important to note that further well-designed RCTs with larger sample sizes are necessary to verify and optimize the current body of evidence.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023396023.
Topics: Female; Humans; Male; Canagliflozin; Diabetes Mellitus, Type 2; Glucose; Nasopharyngitis; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38027214
DOI: 10.3389/fendo.2023.1256548 -
American Family Physician Apr 2024
Topics: Humans; Pharyngitis; Anti-Bacterial Agents
PubMed: 38648823
DOI: No ID Found -
Nature Reviews. Immunology Jun 2024Bacterial T cell superantigens (SAgs) are a family of microbial exotoxins that function to activate large numbers of T cells simultaneously. SAgs activate T cells by... (Review)
Review
Bacterial T cell superantigens (SAgs) are a family of microbial exotoxins that function to activate large numbers of T cells simultaneously. SAgs activate T cells by direct binding and crosslinking of the lateral regions of MHC class II molecules on antigen-presenting cells with T cell receptors (TCRs) on T cells; these interactions alter the normal TCR-peptide-MHC class II architecture to activate T cells in a manner that is independent of the antigen specificity of the TCR. SAgs have well-recognized, central roles in human diseases such as toxic shock syndrome and scarlet fever through their quantitative effects on the T cell response; in addition, numerous other consequences of SAg-driven T cell activation are now being recognized, including direct roles in the pathogenesis of endocarditis, bloodstream infections, skin disease and pharyngitis. In this Review, we summarize the expanding family of bacterial SAgs and how these toxins can engage highly diverse adaptive immune receptors. We highlight recent findings regarding how SAg-driven manipulation of the adaptive immune response may operate in multiple human diseases, as well as contributing to the biology and life cycle of SAg-producing bacterial pathogens.
Topics: Superantigens; Humans; T-Lymphocytes; Receptors, Antigen, T-Cell; Antigens, Bacterial; Lymphocyte Activation; Animals; Histocompatibility Antigens Class II; Bacteria
PubMed: 38225276
DOI: 10.1038/s41577-023-00979-2 -
The Journal of Laryngology and Otology Sep 2023Peritonsillar abscess is a localised infection in the peritonsillar space. Pus from the abscess can contain anaerobes. Many clinicians prescribe metronidazole in... (Review)
Review
BACKGROUND
Peritonsillar abscess is a localised infection in the peritonsillar space. Pus from the abscess can contain anaerobes. Many clinicians prescribe metronidazole in addition to penicillin, but evidence to support this is limited. This review assessed the evidence of benefit of metronidazole for the treatment of peritonsillar abscess.
METHODS
A systematic review was conducted of the literature and databases including Ovid Medline, Ovid Embase, PubMed and Cochrane library. Search terms included all variations of peritonsillar abscess, penicillin and metronidazole.
RESULTS
Three randomised, control trials were included. All studies assessed the clinical outcomes after treatment for peritonsillar abscess, including recurrence rate, length of hospital stay and symptom improvement. There was no evidence to suggest additional benefit with metronidazole, with studies suggesting increased side effects.
CONCLUSION
Evidence does not support the addition of metronidazole in first-line management of peritonsillar abscess. Further trials to establish optimum dose and duration schedules of oral phenoxymethylpenicillin would benefit clinical practice.
Topics: Humans; Peritonsillar Abscess; Metronidazole; Penicillins; Penicillin V; Drainage; Anti-Bacterial Agents
PubMed: 37194922
DOI: 10.1017/S0022215123000804 -
Neuropsychiatric Disease and Treatment 2023Sydenham's chorea (SC) is the most common form of acquired chorea in childhood, it is considered a neurological complication of streptococcal pharyngitis. In this study,...
INTRODUCTION
Sydenham's chorea (SC) is the most common form of acquired chorea in childhood, it is considered a neurological complication of streptococcal pharyngitis. In this study, we aimed to determine the clinical pattern, association of Sydenham's chorea with other manifestations of acute rheumatic fever, and the laboratory findings of Sydenham's chorea among Sudanese patients.
METHODS
A prospective cross-sectional study involving fifty patients of various ages diagnosed with Sydenham's chorea and followed up at The National Center for Neurological Sciences from January 2017 to November 2019. Data were obtained after patients' consent through personal interviews or personal review of patients' records via a structured questionnaire composed of demographic data, symptoms, co-morbid illness, risk factors, physical examination, and related investigations.
RESULTS
About 50 patient was enrolled in this study with a median age of 13.7 years. Females were (n=35) (70%) and (30%) (n=15) s were males. Generalized chorea was seen in 33 (66%) and hemichorea in 17 (34%) patients. Weakness (38%) and hypotonia (46%) were common, such as behavior change (44%), dysarthria (70%), gait change (18%), and deterioration of handwriting (12%). Arthritis occurred in (36%), carditis in 30 (60%), both arthritis and carditis in 18 (36%), and pure chorea in 14 (28%). Erythema marginatum and subcutaneous nodules were not observed in our patients. Only 13 patients (26%) gave a history of pharyngitis.
CONCLUSION
Sydenham chorea is more common in young female Sudanese, with a familial predominance and a tendency towards mitral valve disease. All pediatric Patients with chorea should be screened for Sydenham's chorea.
PubMed: 37525848
DOI: 10.2147/NDT.S417326 -
Infectious Diseases and Therapy Oct 2023Invasive meningococcal disease (IMD) due to serogroup W meningococci (MenW) is consistently reported with atypical clinical manifestations, including gastrointestinal... (Review)
Review
INTRODUCTION
Invasive meningococcal disease (IMD) due to serogroup W meningococci (MenW) is consistently reported with atypical clinical manifestations, including gastrointestinal symptoms, bacteremic pneumonia, and septic arthritis. We undertook a systematic review of the literature for a comprehensive assessment of the clinical presentation of IMD caused by MenW.
METHODS
PubMed and Embase databases were searched from inception to June 2022 using a combination of MeSH terms and free text for articles that reported symptoms and signs of MenW IMD, and associated manifestations.
RESULTS
The most commonly reported symptoms identified included: fever (range 36-100% of cases), nausea and/or vomiting (range 38-47%), vomiting (range 14-68%), cough (range 7-57%), sore throat (range 13-34%), headache (range 7-50%), diarrhea (range 8-47%), altered consciousness/mental status (range 7-38%), stiff neck (range 7-54%), and nausea (range 7-20%). Sepsis (range 15-83% of cases) was the most commonly reported manifestation followed by meningitis (range 5-72%), sepsis and meningitis (range 6-74%), bacteremic pneumonia (range 4-24%), arthritis (range 1-15%), and other manifestations (e.g., pharyngitis/epiglottitis/supraglottitis/tonsillitis/conjunctivitis; range 1-24%). The case fatality rates ranged from 8-40%, and among the survivors 4-14% had long-term sequelae.
CONCLUSIONS
Clinicians need to be aware of the nonspecific symptoms and signs of IMD, as well as of the atypical manifestations in regions where MenW is known to circulate to ensure timely diagnoses and treatment.
PubMed: 37751017
DOI: 10.1007/s40121-023-00869-z -
The Cochrane Database of Systematic... Nov 2023Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic... (Review)
Review
BACKGROUND
Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2021.
OBJECTIVES
To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2023, Issue 2), MEDLINE Ovid, Embase Elsevier, and Web of Science (Clarivate) up to 19 March 2023.
SELECTION CRITERIA
Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures recommended by Cochrane. We assessed the risk of bias in the included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results.
MAIN RESULTS
We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both, heterogeneity, and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials, 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials, 1660 participants; very low-certainty evidence). Based on an analysis of evaluable participants, we are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials, 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials, 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79 (95% CI 0.57 to 1.09; 6 trials, 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials, 802 participants; low-certainty evidence). Children treated with macrolides seemed to experience more adverse events than those treated with penicillin (OR 2.33, 95% CI 1.06 to 5.15; 1 trial, 489 participants; low-certainty evidence). However, the test for subgroup differences between children and adults was not significant. Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial, 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29 (95% CI 0.11 to 0.73; 1 trial, 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial, 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial, 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials, 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better at preventing serious but rare complications.
AUTHORS' CONCLUSIONS
We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. Antibiotics have a limited effect in the treatment of GABHS pharyngitis and the results do not demonstrate that other antibiotics are more effective than penicillin. In the context of antimicrobial stewardship, penicillin can be used if treatment with an antibiotic is indicated. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and disadvantaged populations, where the risk of complications remains high.
Topics: Adult; Child; Humans; Infant; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Chronic Disease; Macrolides; Penicillins; Pharyngitis; Randomized Controlled Trials as Topic; Recurrence; Streptococcus pyogenes; Systematic Reviews as Topic
PubMed: 37965935
DOI: 10.1002/14651858.CD004406.pub6 -
Pediatric Reports Mar 2024Lemierre syndrome is a rare, potentially fatal complication of oropharyngeal infections characterized by septic thrombophlebitis of the internal jugular vein. It... (Review)
Review
BACKGROUND
Lemierre syndrome is a rare, potentially fatal complication of oropharyngeal infections characterized by septic thrombophlebitis of the internal jugular vein. It primarily affects healthy adolescents and young adults. Its incidence declined after the antibiotic era, but it may have resurged in recent decades, likely due to judicious antibiotic use and increasing bacterial resistance. Prompt diagnosis and treatment are imperative to prevent significant morbidity and mortality.
METHODS
Lemierre syndrome has been called "the forgotten disease," with a reported incidence of around 3.6 cases per million. The mean age at presentation is around 20 years old, though it can occur at any age. Lemierre Syndrome follows an oropharyngeal infection, most commonly pharyngitis, leading to septic thrombophlebitis of the internal jugular vein. is the classic pathogen, though other organisms are being increasingly isolated. Metastatic infections, especially pulmonary, are common complications. Contrast-enhanced CT of the neck confirming internal jugular vein thrombosis is the gold standard for diagnosis. Long-course broad-spectrum IV antibiotics covering anaerobes are the mainstays of the disease's treatment. Anticoagulation may also be considered. Mortality rates are high without treatment, but most patients recover fully with appropriate therapy.
CONCLUSIONS
Lemierre syndrome should be suspected in patients with prolonged pharyngitis followed by unilateral neck swelling and fevers. Early diagnosis and prompt antibiotic therapy are key, given the potential for disastrous outcomes if untreated. An increased awareness of Lemierre syndrome facilitates its timely management.
PubMed: 38535514
DOI: 10.3390/pediatric16010018