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International Journal of Infectious... May 2024The objective was to estimate the probability that finding a Streptococcus pyogenes (Group A Streptococcus) in a throat swab in a patient with a sore throat reflects the...
OBJECTIVES
The objective was to estimate the probability that finding a Streptococcus pyogenes (Group A Streptococcus) in a throat swab in a patient with a sore throat reflects the aetiology. We also investigated to what extent this is influenced by age, carrier rates of S. pyogenes and climate zone.
METHODS
We conducted a comprehensive search of Medline and Scopus up until October 2023 for case-control studies reporting the prevalence of S. pyogenes in patients with a sore throat and healthy controls. We only included studies with separate data for children and adults. We used the positive and negative etiologic predictive value (P-EPV and N-EPV) to estimate the probability of a link between a sore throat and a finding of S. pyogenes.
RESULTS
We included 15 studies in our meta-analysis. The overall P-EPV for children and adults were 63% (49-74%) and 92% (87-95%), respectively. The P-EPV rose to 83% (64-93%) for children and 94% (90-97%) for adults when only patients with 3-4 Centor criteria were included. The overall N-EPV was 97% (96-98%) for children and 96% (95-97%) for adults.
CONCLUSIONS
Detecting S. pyogenes in adult patients with an uncomplicated acute sore throat is useful to rule in S. pyogenes as the likely aetiologic agent. The P-EPV significantly increased for children when those with 3-4 Centor criteria were selected. A negative throat swab is always useful for both children and adults to rule out S. pyogenes as the cause of the sore throat.
PubMed: 38762046
DOI: 10.1016/j.ijid.2024.107100 -
Ear, Nose, & Throat Journal May 2024A 48-year-old man diagnosed with rheumatoid arthritis was treated with methotrexate for 10 years. He presented left tonsil ulceration and ipsilateral cervical...
A 48-year-old man diagnosed with rheumatoid arthritis was treated with methotrexate for 10 years. He presented left tonsil ulceration and ipsilateral cervical lymphadenopathy. A tonsillar biopsy revealed tuberculosis. The patient received antituberculous therapy for 8 months with a positive response. However, after resumption of methotrexate due to worsening rheumatoid arthritis, symptoms recurred. The patient initiated antituberculous therapy once more for 6 months, and methotrexate was stopped. At regular follow-up, the patient showed a positive clinical response with resolution of tonsillar ulceration and lymphadenopathy after 14 months of antituberculosis treatment.
PubMed: 38757686
DOI: 10.1177/01455613241254685 -
Antimicrobial Agents and Chemotherapy May 2024Cell culture-based screening of a chemical library identified diphenoxylate as an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)....
Cell culture-based screening of a chemical library identified diphenoxylate as an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The observed 50% effective concentrations ranged between 1.4 and 4.9 µM against the original wild-type strain and its variants. Time-of-addition experiments indicated that diphenoxylate is an entry blocker targeting a host factor involved in viral infection. Fluorescence microscopic analysis visualized that diphenoxylate prevented SARS-CoV-2 particles from penetrating the cell membrane and also impaired endo-lysosomal acidification. Diphenoxylate exhibited a synergistic inhibitory effect on SARS-CoV-2 infection in human lung epithelial Calu-3 cells when combined with a transmembrane serine protease 2 (TMPRSS2) inhibitor, nafamostat. This synergy suggested that efficient antiviral activity is achieved by blocking both TMPRSS2-mediated early and endosome-mediated late SARS-CoV-2 entry pathways. The antiviral efficacy of diphenoxylate against SARS-CoV-2 was reproducible in a human tonsil organoids system. In a transgenic mouse model expressing the obligate SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, intranasal administration of diphenoxylate (10 mg/kg/day) significantly reduced the viral RNA copy number in the lungs by 70% on day 3. This study underscores that diphenoxylate represents a promising core scaffold, warranting further exploration for chemical modifications aimed at developing a new class of clinically effective antiviral drugs against SARS-CoV-2.
PubMed: 38742905
DOI: 10.1128/aac.00341-24 -
Frontiers in Pediatrics 2024Group A streptococcus (GAS) infections, such as pharyngitis and impetigo, can lead to rheumatic fever and rheumatic heart disease (RHD). Australian Aboriginal and Torres...
INTRODUCTION
Group A streptococcus (GAS) infections, such as pharyngitis and impetigo, can lead to rheumatic fever and rheumatic heart disease (RHD). Australian Aboriginal and Torres Strait Islander populations experience high rates of RHD and GAS skin infection, yet rates of GAS pharyngitis are unclear. Anecdotally, clinical presentations of pharyngitis, including tonsillar hypertrophy and sore throat, are uncommon. This study aimed to develop a standardised set of tonsil photographs and determine tonsil size distribution from an urban paediatric population.
METHODS
A prospective cohort of children aged 3-15 years were recruited at the public events "Discover Day" and "Telethon Weekend" (October 2017) in Perth, Western Australia, Australia. Tonsil photographs, symptomatology, and GAS rapid antigen detection tests (RADT) were collected. Tonsil size was graded from the photographs using the Brodsky Grading Scale of tonsillar hypertrophy (Brodsky) by two independent clinicians, and inter-rater reliability calculated. Pharyngitis symptoms and GAS RADT were correlated, and immediate results provided.
RESULTS
Four hundred and twenty-six healthy children participated in the study over three days. The median age was seven years [interquartile range (IQR) 5.9-9.7 years]. Tonsil photographs were collected for 92% of participants, of which 62% were rated as good-quality photographs and 79% were deemed of adequate quality for assessment by both clinicians. When scored by two independent clinicians, 57% received the same grade. Average Brodsky grades (between clinicians) were 11%, 35%, 28%, 22% and 5% of grades 0,1,2,3 and 4, respectively. There was moderate agreement in grading using photographs, and minimal to weak agreement for signs of infection. Of 394 participants, 8% reported a sore throat. Of 334 GAS RADT performed, <1% were positive.
DISCUSSION
We report the first standardised use of paediatric tonsil photographs to assess tonsil size in urban-living Australian children. This provides a proof of concept from an urban-living cohort that could be compared with children in other settings with high risk of GAS pharyngitis or rheumatic fever such as remote-living Australian Indigenous populations.
PubMed: 38725980
DOI: 10.3389/fped.2024.1367060 -
International Journal of Surgery Case... Apr 2024Polymorphous low-grade adenocarcinoma (PLGA) is a rare neoplasm arising from minor salivary glands, representing approximately 3 % of head and neck tumors. The clinical...
INTRODUCTION AND IMPORTANCE
Polymorphous low-grade adenocarcinoma (PLGA) is a rare neoplasm arising from minor salivary glands, representing approximately 3 % of head and neck tumors. The clinical presentation of PLGA is defined as a painless, slow-growing tumor, mostly occurring in the palate. We report a case of PLGA with a rare presentation.
CASE PRESENTATION
A 76-year-old male, known case of hepatitis B, diabetes, and hypertension, presented to the emergency department complaining of spitting blood and dysphagia. Imaging showed a heterogeneous enlarged left tonsil with hyperemia of the mucosa, and air foci. Biopsy with excisional biopsy confirmed the diagnosis of PLGA. The patient underwent completion tonsillectomy and selective neck dissection which yielded tonsillar tissue with underlying PLGA, and reactive lymph nodes with no malignant tissue respectively, margins were negative for malignancy.
CLINICAL DISCUSSION
Polymorphous low-grade adenocarcinoma is a rare lesion with clinical behavior resembling that of a benign neoplasm. Predominantly occurring in the oral cavity, especially on the hard palate, buccal mucosa, and retromolar region, with fewer cases in the upper lip. Occurrence in the nasopharynx and oropharynx is rare. PLGA presents as painless slow-growing masses, typically in females aged 50-60. Local excision with careful margin evaluation is the preferred treatment, with good prognosis compared to other carcinomas.
CONCLUSION
PLGA is rare, with limited reported case from around the world. It is mostly seen in adults between their fifth and sixth decades with female predominance. PLGA is diagnosed using imaging, immunohistochemistry. Owing to the limited cases there is no standard approach to treating PLGA. However, most cases are managed with local excision and showed an excellent response in terms of tumor nonrecurrence.
PubMed: 38723440
DOI: 10.1016/j.ijscr.2024.109647 -
Chinese Medicine May 2024Thesium chinense Turcz. (Named as Bai Rui Cao in Chinese) and its preparations (e.g., Bairui Granules) have been used to treat inflammatory diseases, such as acute...
BACKGROUND
Thesium chinense Turcz. (Named as Bai Rui Cao in Chinese) and its preparations (e.g., Bairui Granules) have been used to treat inflammatory diseases, such as acute mastitis, lobar pneumonia, tonsillitis, coronavirus disease 2019 (COVID-19), and upper respiratory tract infection. However, the material basis, pharmacological efficiency, and safety have not been illustrated.
METHODS
Anti-inflammatory activity-guided isolation of constituents has been performed using multiple column chromatography, and their structures were elucidated by NMR spectroscopy and ECD calculations. The inhibitory effects on lung inflammation and safety of the crude ethanol extract (CE), Bairui Granules (BG), and the purified active constituents were evaluated using lipopolysaccharide (LPS)-stimulated acute lung inflammation (ALI) mice model or normal mice.
RESULTS
Seven new compounds (1-7) and fifty-six known compounds (8-63) were isolated from T. chinense, and fifty-four were reported from this plant for the first time. The new flavonoid glycosides 1-2, new fatty acids 4-5, new alkaloid 7 as well as the known constituents including flavonoid aglycones 8-11, lignans 46-54, alkaloids 34 and 45, coumarins 57, phenylpropionic acids 27, and simple aromatic compounds 39, 44 and 58 exhibited anti-inflammatory activity. Network pharmacology analysis indicated that anti-inflammation of T. chinense was attributed to flavonoids and alkaloids by regulating inflammation-related proteins (e.g., TNF, NF-κB, TGF-β). Furthermore, constituents of T. chinense including kaempferol-3-O-glucorhamnoside (KN, also named as Bairuisu I, 19), astragalin (AG, Bairuisu II, 12), and kaempferol (KF, Bairuisu III, 8), as well as CE and BG could alleviate lung inflammation caused by LPS in mice by preventing neutrophils infiltration and the expression of the genes for pro-inflammatory cytokines NLRP3, caspase-1, IL-1β, and COX-2. After a 28-day subacute toxicity test, BG at doses of 4.875 g/kg and 9.750 g/kg (equivalent to onefold and twofold the clinically recommended dose) and CE at a dose of 11.138 g/kg (equivalent to fourfold the clinical dose of BG) were found to be safe and non-toxic.
CONCLUSIONS
The discovery of sixty-three constituents comprehensively illustrated the material basis of T. chinense. T. chinense and Bairui Granules could alleviate lung inflammation by regulating inflammation-related proteins and no toxicity was observed under the twofold of clinically used doses.
PubMed: 38720376
DOI: 10.1186/s13020-024-00940-y -
Poultry Science Apr 2024The objective of this study was to evaluate the effect of 25% arginine supplementation as a functional amino acid in partially alleviating the detrimental effects of...
The objective of this study was to evaluate the effect of 25% arginine supplementation as a functional amino acid in partially alleviating the detrimental effects of necrotic enteritis (NE) on the growth performance, serum biochemistry, gut integrity, and the relative gene expression of tight junction proteins and inflammatory cytokines in broilers during NE. Three hundred and sixty 1-day-old chicks were randomly allocated to 4 treatments in a 2 × 2 factorial arrangement -basal diet and 125% arginine diet, with or without NE challenge. NE was induced by inoculating 1 × 10Eimeria maxima sporulated oocysts on d 14 and 1 × 10 CFU/bird C. perfringens on d 19, 20, and 21. The NE challenge had a significant effect on the BWG (p < 0.05), FCR (p < 0.05), serum AST (p < 0.05), GLU (p < 0.05), and K (p < 0.05) levels, and intestinal permeability (p < 0.05) and jejunal lesion score (p < 0.05). A significant challenge × diet interaction effect was observed in the cecal tonsil CD8: CD4 T-cell ratio on d 21 (p < 0.05) and 28 (p < 0.05) and spleen CD8: CD4 T-cell ratio on d 21 (p < 0.05) and 35 (p < 0.05). Arginine supplementation significantly increased the CD8: CD4 T-cell ratio in uninfected birds but decreased the CD8: CD4 T-cell ratio in infected birds. On d 21, a significant interaction effect was observed on the relative expression of the iNOS gene (p < 0.05). Arginine supplementation significantly downregulated the expression of the iNOS gene in infected birds. A significant effect of the challenge (p < 0.05) was observed on the relative gene expression of the ZO-1 gene in the jejunum. NE challenge significantly downregulated the expression of the ZO-1 gene on d 21. In conclusion, arginine supplementation did not alleviate the depression in growth performance and disease severity during the NE challenge. However, arginine downregulated the expression of inflammatory cytokines and enzymes, preventing inflammatory injury to the tissues during NE. Hence, arginine might be supplemented with other alternatives to downregulate inflammatory response during NE in poultry.
PubMed: 38713988
DOI: 10.1016/j.psj.2024.103815 -
Acta Otorhinolaryngologica Italica :... May 2024Studies have demonstrated that tonsillectomy may alter the risk of oropharyngeal cancer (OPC). We systematically reviewed the evidence and pooled data to examine such an... (Review)
Review
OBJECTIVE
Studies have demonstrated that tonsillectomy may alter the risk of oropharyngeal cancer (OPC). We systematically reviewed the evidence and pooled data to examine such an association.
METHODS
PubMed, Embase, and Scopus were searched up to 25 April 2023. Studies reporting an association between tonsillectomy and oropharyngeal cancer risk at any site were included.
RESULTS
Five studies were eligible. All examined the risk of tonsillar and base of the tongue (BOT) cancer with prior history of tonsillectomy. On meta-analysis of the data, prior history of tonsillectomy was associated with a significantly decreased risk of tonsillar cancer. The second meta-analysis showed that history of tonsillectomy did not significantly alter the risk of BOT cancer. However, after exclusion of one study, the results showed an increased risk of BOT cancer with a history of tonsillectomy.
CONCLUSIONS
The scarce data available in the literature suggests that tonsillectomy may reduce the risk of tonsillar cancer but does not alter the risk of BOT cancer. Further studies are needed to explore the association between tonsillectomy and the risk of OPC.
PubMed: 38712770
DOI: 10.14639/0392-100X-N2790 -
Journal of Translational Medicine May 2024Programmed cell death 1 (PD-1) belongs to immune checkpoint proteins ensuring negative regulation of the immune response. In non-small cell lung cancer (NSCLC), the...
BACKGROUND
Programmed cell death 1 (PD-1) belongs to immune checkpoint proteins ensuring negative regulation of the immune response. In non-small cell lung cancer (NSCLC), the sensitivity to treatment with anti-PD-1 therapeutics, and its efficacy, mostly correlated with the increase of tumor infiltrating PD-1 lymphocytes. Due to solid tumor heterogeneity of PD-1 populations, novel low molecular weight anti-PD-1 high-affinity diagnostic probes can increase the reliability of expression profiling of PD-1 tumor infiltrating lymphocytes (TILs) in tumor tissue biopsies and in vivo mapping efficiency using immune-PET imaging.
METHODS
We designed a 13 kDa β-sheet Myomedin scaffold combinatorial library by randomization of 12 mutable residues, and in combination with ribosome display, we identified anti-PD-1 Myomedin variants (MBA ligands) that specifically bound to human and murine PD-1-transfected HEK293T cells and human SUP-T1 cells spontaneously overexpressing cell surface PD-1.
RESULTS
Binding affinity to cell-surface expressed human and murine PD-1 on transfected HEK293T cells was measured by fluorescence with LigandTracer and resulted in the selection of most promising variants MBA066 (hPD-1 KD = 6.9 nM; mPD-1 KD = 40.5 nM), MBA197 (hPD-1 KD = 29.7 nM; mPD-1 KD = 21.4 nM) and MBA414 (hPD-1 KD = 8.6 nM; mPD-1 KD = 2.4 nM). The potential of MBA proteins for imaging of PD-1 populations in vivo was demonstrated using deferoxamine-conjugated MBA labeled with Galium isotope. Radiochemical purity of Ga-MBA proteins reached values 94.7-99.3% and in vitro stability in human serum after 120 min was in the range 94.6-98.2%. The distribution of Ga-MBA proteins in mice was monitored using whole-body positron emission tomography combined with computerized tomography (PET/CT) imaging up to 90 min post-injection and post mortem examined in 12 mouse organs. The specificity of MBA proteins was proven by co-staining frozen sections of human tonsils and NSCLC tissue biopsies with anti-PD-1 antibody, and demonstrated their potential for mapping PD-1 populations in solid tumors.
CONCLUSIONS
Using directed evolution, we developed a unique set of small binding proteins that can improve PD-1 diagnostics in vitro as well as in vivo using PET/CT imaging.
Topics: Humans; Programmed Cell Death 1 Receptor; Animals; Positron-Emission Tomography; HEK293 Cells; Protein Engineering; Mice; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Lung Neoplasms; Amino Acid Sequence
PubMed: 38711085
DOI: 10.1186/s12967-024-05210-x -
PloS One 2024Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for...
BACKGROUND
Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for antigen-specific humoral immune responses in the palatine tonsils. Germinal center involution is frequently observed in the palatine tonsils of IgAN (IgAN tonsils). However, the pathogenic significance of these characteristic changes remains unclear. This study aimed to investigate the morphological changes in secondary lymphoid follicles in IgAN tonsils and to evaluate the correlation between the morphometric results and the clinicopathological severity of IgAN.
METHODS
The tonsils of age-matched patients with recurrent tonsillitis (RT tonsils) were used as controls. The correlation between the degree of lymphoid follicular involution and histopathological severities in clinical or kidney biopsy was evaluated.
RESULTS
In total, 87 patients with IgAN were included (48% male, median age 35 years, median estimated glomerular filtration rate: 74 mL/min/1.73 m2). Compared to RT tonsils, IgAN tonsils showed smaller median sizes of lymphoid follicles and germinal centers (P < 0.001). The relative areas of lymphoid follicles (%LFA) and germinal centers (%GCA) in the total tonsillar tissue were smaller in the IgAN tonsils than in the RT tonsils (P < 0.001). In contrast, the median proportion of mantle zones in the total tonsillar tissue was comparable between the groups. A lower %LFA was associated with a longer period from the onset of urinary abnormalities to biopsy diagnosis and higher urinary protein excretion (P = 0.01). %LFA showed significant negative correlations with frequencies of glomeruli with both global and segmental sclerosis.
CONCLUSIONS
The present study confirmed accelerated germinal center involution in the tonsils of patients with IgAN. This characteristic change in the IgAN tonsil correlates with heavy proteinuria and advanced chronic histopathological changes in the kidneys, thereby suggesting the involvement of repeated tonsillar immunoreactions during IgAN progression.
Topics: Humans; Glomerulonephritis, IGA; Palatine Tonsil; Germinal Center; Male; Female; Adult; Tonsillitis; Middle Aged; Young Adult; Kidney
PubMed: 38709804
DOI: 10.1371/journal.pone.0301853