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Immunity Aug 2021Lymphoid stromal cells (LSCs) are essential organizers of immune responses. We analyzed tonsillar tissue by combining flow cytometry, in situ imaging, RNA sequencing,...
Lymphoid stromal cells (LSCs) are essential organizers of immune responses. We analyzed tonsillar tissue by combining flow cytometry, in situ imaging, RNA sequencing, and functional assays, defining three distinct human LSC subsets. The integrin CD49a designated perivascular stromal cells exhibiting features of local committed LSC precursors and segregated cytokine and chemokine-producing fibroblastic reticular cells (FRCs) supporting B and T cell survival. The follicular dendritic cell transcriptional profile reflected active responses to B cell and non-B cell stimuli. We therefore examined the effect of B cell stimuli on LSCs in follicular lymphoma (FL). FL B cells interacted primarily with CD49a FRCs. Transcriptional analyses revealed LSC reprogramming in situ downstream of the cytokines tumor necrosis factor (TNF) and transforming growth factor β (TGF-β), including increased expression of the chemokines CCL19 and CCL21. Our findings define human LSC populations in healthy tissue and reveal bidirectional crosstalk between LSCs and malignant B cells that may present a targetable axis in lymphoma.
Topics: B-Lymphocytes; Cells, Cultured; Chemokine CCL19; Chemokine CCL21; Dendritic Cells; Humans; Integrin alpha1; Lymphoma, Follicular; Palatine Tonsil; Signal Transduction; Stromal Cells; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha
PubMed: 34166622
DOI: 10.1016/j.immuni.2021.05.019 -
Emerging Microbes & Infections Dec 2023Cytokine dynamics in patients with coronavirus disease 2019 (COVID-19) have been studied in blood but seldomly in respiratory specimens. We studied different cell...
Correlations of Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in the nasopharyngeal specimens with the diagnosis and severity of SARS-CoV-2 infections.
Cytokine dynamics in patients with coronavirus disease 2019 (COVID-19) have been studied in blood but seldomly in respiratory specimens. We studied different cell markers and cytokines in fresh nasopharyngeal swab specimens for the diagnosis and for stratifying the severity of COVID-19. This was a retrospective case-control study comparing Myeloperoxidase (MPO), Adenosine deaminase (ADA), C-C motif chemokine ligand 22 (CCL22), Tumour necrosis factor alpha (TNFα) and Interleukin-6 (IL-6) mRNA expression in 490 (327 patients and 163 control) nasopharyngeal specimens from 317 (154 COVID-19 and 163 control) hospitalized patients. Of the 154 COVID-19 cases, 46 died. Both total and normalized MPO, ADA, CCL22, TNFα, and IL-6 mRNA expression levels were significantly higher in the nasopharyngeal specimens of infected patients when compared with controls, with ADA showing better performance (OR 5.703, 95% CI 3.424-9.500, < 0.001). Receiver operating characteristics (ROC) curve showed that the cut-off value of normalized ADA mRNA level at 2.37 × 10 had a sensitivity of 81.8% and specificity of 83.4%. While patients with severe COVID-19 had more respiratory symptoms, and elevated lactate dehydrogenase, multivariate analysis showed that severe COVID-19 patients had lower CCL22 mRNA (OR 0.211, 95% CI 0.060-0.746, = 0.016) in nasopharyngeal specimens, while lymphocyte count, C-reactive protein, and viral load in nasopharyngeal specimens did not correlate with disease severity. In summary, ADA appears to be a better biomarker to differentiate between infected and uninfected patients, while CCL22 has the potential in stratifying the severity of COVID-19.
Topics: Humans; COVID-19; Interleukin-6; Tumor Necrosis Factor-alpha; Retrospective Studies; Adenosine Deaminase; Case-Control Studies; Peroxidase; Ligands; SARS-CoV-2; Cytokines; Chemokines; Nasopharynx; Chemokine CCL22
PubMed: 36482706
DOI: 10.1080/22221751.2022.2157338 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Jul 2022Because of its peculiar anatomical location, most patients with hypopharyngeal and cervical esophageal cancer are at advanced stage when they visit the hospital. At...
OBJECTIVES
Because of its peculiar anatomical location, most patients with hypopharyngeal and cervical esophageal cancer are at advanced stage when they visit the hospital. At present, the treatment for hypopharyngeal and cervical esophageal cancer is primarily surgical resection and radiotherapy. However, due to the wide range of surgical resection, it can often lead to a large range of annular defects. Therefore, the upper digestive tract reconstruction after tumor resection is very important. We use the free anterolateral thigh flap (ALT) and free jejunum (FJ) transfer to reconstruct the hypopharyngeal and cervical esophagus, and to investigate the effect of both reconstruction methods on upper gastrointestinal tract defects.
METHODS
A retrospective analysis was conducted to investigate the clinical data of 42 patients with hypopharyngeal and cervical esophageal cancer (Clinical Stage IV) from Jan. 2004 to Jan. 2016 in the Second Xiangya Hospital of Central South University. All patients underwent total laryngopharyngectomy and cervical esophageal resection. The hypopharyngeal circumferential and cervical esophageal defects were reconstructed with free ALT (=22) or FJ (=20). Four patients who underwent radiotherapy and chemotherapy before surgery did not receive radiotherapy or chemotherapy after surgery. The remaining 38 patients underwent postoperative radiotherapy and chemotherapy. All patients were followed up by telephone or outpatient review, with a follow-up deadline in Jan. 2021. We compared the differences between the 2 groups in postoperative complications, radiotherapy complications, and survival rate. The differences in individual characteristics between 2 groups were analyzed using Fisher test. The differences in postoperative and radiotherapy complications between two groups were analyzed using χ² test. The 3- and 5-year overall survival rates were calculated using Kaplan-Meier survival curve method.
RESULTS
In the ALT group, the postoperative complications mainly included anastomotic fistula, chylous fistula and subcutaneous hematoma of the donor site. The radiotherapy complication was anastomotic stenosis. However, in the FJ group, the postoperative complications mainly included chylous fistula, intestinal obstruction, and intestinal fistula. The radiotherapy complications mainly contained anastomotic fistula and tissue flap necrosis. The cases of postoperative complications in the ALT group and the FJ group were 7 and 5, respectively (=0.625), and the cases of radiotherapy complications were 3 and 4, respectively (=0.563). The 3-year overall survival rates in the ALT group and the FJ group were 52.9% and 46.7%, respectively, and the 5-year total survival rates were 35.1% and 31.9%, respectively (=0.53). The cases of anastomotic stenosis after radiotherapy in the ALT group were more than those in the FJ group (=0.097). However, the cases of jejunal necrosis and anastomotic fistula after radiotherapy in the FJ group were more than those in the ALT group (=0.066).
CONCLUSIONS
There are no significant differences in postoperative and radiotherapy complications and 3-and 5-year survival rates between the ALT group and the FJ group. The reconstruction with ALT is prone to develop anastomotic stricture. The reconstruction with FJ cannot withstand high-dose radiotherapy. The ALT and FJ are effective methods in the reconstruction of hypopharynx and cervical esophagus. The treatment protocol should be carefully chosen based on its advantages and disadvantages of these 2 methods.
Topics: Constriction, Pathologic; Esophageal Neoplasms; Fistula; Free Tissue Flaps; Humans; Hypopharynx; Jejunum; Necrosis; Postoperative Complications; Plastic Surgery Procedures; Retrospective Studies; Thigh
PubMed: 36039585
DOI: 10.11817/j.issn.1672-7347.2022.210763 -
Ear, Nose, & Throat Journal Jan 2020The laryngopharyngeal reconstruction in patients with pyriform sinus carcinoma continues to be a challenge for surgeons. In this article, we describe our experience with...
The laryngopharyngeal reconstruction in patients with pyriform sinus carcinoma continues to be a challenge for surgeons. In this article, we describe our experience with laryngopharyngeal reconstruction in patients with pyriform sinus carcinoma using the modified infrahyoid myocutaneous flap (IHMCF). The modified incision design for the modified IHMCF and clinical outcomes are also detailed here. Between January 2012 and February 2018, 10 patients with hypopharyngeal squamous cell carcinoma who underwent laryngopharyngeal reconstruction using the modified IHMCF after hemicricolaryngopharyngectomy were included in this study. The drainage vessels of the modified IHMCF, oncological outcomes, and functional reservation of the larynx were recorded. All of the flaps survived well. No flap necrosis or other major complications occurred during follow-up. None of the patients remained on nasogastric feeding for more than 4 weeks postoperatively. The follow-up period ranged from 12 to 73 months (mean, 36 months). In our series, 6 patients were successfully decannulated and 5 had received radiation therapy. We roughly assessed the speech and swallowing functions, and the outcomes seemed acceptable in all of the patients after surgery. Laryngoscopic examination showed that the modified IHMCF survived well and the new glottis provided excellent function and good ventilation results. In our experience, the modified IHMCF is a safe and viable procedure that can serve as a valid alternative to free flaps and the pectoralis major myocutaneous flap to reconstruct laryngopharyngeal defects.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Humans; Hyoid Bone; Hypopharyngeal Neoplasms; Hypopharynx; Laryngoplasty; Larynx; Male; Middle Aged; Myocutaneous Flap; Plastic Surgery Procedures; Treatment Outcome
PubMed: 31079475
DOI: 10.1177/0145561319849947 -
Dysphagia Oct 2022Lateral medullary syndrome/Wallenberg syndrome is a stroke in the lateral medulla with symptoms often including dysphagia and dysphonia. In adults, this stroke is the...
Lateral medullary syndrome/Wallenberg syndrome is a stroke in the lateral medulla with symptoms often including dysphagia and dysphonia. In adults, this stroke is the most common brainstem stroke, but it is rare in the pediatric population. Insults to the medulla can involve the "swallowing centers," the nucleus ambiguus and nucleus tractus solitarius, and the cranial nerves involved in swallowing, namely IX (glossopharyngeal) and X (vagus). These individuals can develop severe dysphagia with an inability to trigger a swallow due to pharyngeal weakness and impaired mechanical opening of the upper esophageal sphincter (UES) which can result in aspiration. We present a 7-year-old male with 22q11.2 deletion syndrome (velocardiofacial syndrome) and velopharyngeal insufficiency who underwent pharyngeal flap surgery at an outside hospital whose post-operative course was complicated by adenovirus, viral myocarditis, and dorsal medullary stroke. He required a tracheostomy and gastrostomy tube. He was discharged from that hospital and readmitted to our hospital 4 months later for increased oxygen requirement, requiring a 5 month admission in the intensive care units. His initial VFSS revealed absent UES opening with the entire bolus remaining in the pyriform sinuses resulting in aspiration. His workup over the course of his admission included multiple videofluoroscopic swallow studies (VFSS), flexible endoscopic evaluation of swallowing (FEES), and pharyngeal and esophageal manometry. Intervention included intensive speech therapy, cricopharyngeal Botox® injection, and cricopharyngeal myotomy. Nineteen months after his stroke, he transitioned to oral intake of solids and liquids with adequate movement of the bolus through the pharynx and UES and no aspiration on his VFSS.
Topics: Adult; Brain Stem Infarctions; Child; Deglutition; Deglutition Disorders; Esophageal Sphincter, Upper; Humans; Lateral Medullary Syndrome; Male; Manometry; Stroke
PubMed: 34705083
DOI: 10.1007/s00455-021-10376-3 -
Journal of Medical Virology Jan 2020This study aimed to assess the clinical characteristics and T-helper 1 (Th1)/Th2 profile of human rhinovirus (HRV) infection in children with bronchiolitis and... (Comparative Study)
Comparative Study
This study aimed to assess the clinical characteristics and T-helper 1 (Th1)/Th2 profile of human rhinovirus (HRV) infection in children with bronchiolitis and pneumonia, compared with the respiratory syncytial virus (RSV). In September 2013 to August 2014, 335 nasopharyngeal aspirates from children below 14 with bronchiolitis and pneumonia were screened for HRV and 13 other respiratory viruses by PCR or reverse transcription PCR. Interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF)-α were detected by multiplex enzyme-linked immunosorbent assay. HRVs were found in 66 cases (19.7%), including 35 bronchiolitis and 31 pneumonia cases. Compared with the RSV alone group, children with pneumonia had more frequent wheezing episodes in HRV (P = .001) and HRV + non-RSV (P = .002) groups, and fever in the HRV (P = .004) and HRV + RSV (P = .005) groups. Among patients with bronchiolitis, cases with HRV alone were more likely to present in winter than those with RSV alone (P = .010) and HRV + non-RSV (P = .014), and less numerous in summer compared with HRV + non-RSV (P = .005). Children with HRV alone were more susceptible to have a history of eczema than RSV alone among bronchiolitis (P < .001) and pneumonia (P = .033) cases. HRV bronchiolitis cases had increased IL-4/IFN-γ and decreased TNF-α/IL-10 ratios, compared with HRV pneumonia counterparts. HRV is a major non-RSV pathogen causing hospitalization in children with bronchiolitis and pneumonia and induces an imbalanced Th1/Th2 response in bronchiolitis. Compared with RSV infection, HRV bronchiolitis and pneumonia differ significantly regarding wheezing episodes, susceptibility to eczema, fever occurrence, and seasonal prevalence.
Topics: Adolescent; Bronchiolitis; Child; Child, Preschool; Cytokines; Eczema; Female; Fever; Hospitalization; Humans; Infant; Infant, Newborn; Male; Nasopharynx; Picornaviridae Infections; Pneumonia, Viral; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Rhinovirus; Severity of Illness Index; Th1 Cells; Th2 Cells
PubMed: 31475732
DOI: 10.1002/jmv.25587 -
Frontiers in Immunology 2021In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral...
In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral cavity, oropharynx, esophagus, stomach and bowel. In this report, we describe an autopsy case of a COVID-19 patient who showed two undiagnosed ulcers at the level of the anterior and posterior walls of the hypopharynx. Molecular testing of viruses involved in pharyngeal ulcers demonstrated the presence of severe acute respiratory syndrome - coronavirus type 2 (SARS-CoV-2) RNA, together with herpes simplex virus 1 DNA. Histopathologic analysis demonstrated full-thickness lympho-monocytic infiltration (mainly composed of CD68-positive cells), with hemorrhagic foci and necrosis of both the mucosal layer and deep skeletal muscle fibers. Fibrin and platelet microthrombi were also found. Cytological signs of HSV-1 induced damage were not found. Cells expressing SARS-CoV-2 spike subunit 1 were immunohistochemically identified in the inflammatory infiltrations. Immunohistochemistry for HSV1 showed general negativity for inflammatory infiltration, although in the presence of some positive cells. Thus, histopathological, immunohistochemical and molecular findings supported a direct role by SARS-CoV-2 in producing local ulcerative damage, although a possible contributory role by HSV-1 reactivation cannot be excluded. From a clinical perspective, this autopsy report of two undiagnosed lesions put the question if ulcers along the GI tract could be more common (but frequently neglected) in COVID-19 patients.
Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Autopsy; Blood Platelets; COVID-19; Gastrointestinal Tract; Herpesvirus 1, Human; Humans; Hypopharynx; Immunohistochemistry; Inflammation; Lymphocytes; Monocytes; Mucous Membrane; Muscle, Skeletal; Necrosis; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Thrombosis; Ulcer
PubMed: 34290701
DOI: 10.3389/fimmu.2021.676828 -
Cureus Sep 2023Toxic epidermal necrolysis (TEN) is a life-threatening, blistering dermatitis. It is characterized by fever and the development of mucocutaneous lesions, which lead to...
Toxic epidermal necrolysis (TEN) is a life-threatening, blistering dermatitis. It is characterized by fever and the development of mucocutaneous lesions, which lead to necrosis and sloughing of the epidermis. It is commonly triggered by medications and infections. We present the case of a 75-year-old male who presented to the hospital with a fever and widespread exfoliating skin rash involving 41% of his body surface area (BSA). He has a past medical history of gout, hypertension, asthma, and depression. He was recently started on allopurinol by his general practitioner (GP) for hyperuricemia. The condition also involved oral, eye, and pharynx mucosae. He was diagnosed with toxic epidermal necrolysis and was managed with intravenous (IV) hydrocortisone, steroid and antibiotic eye drops, and steroid and antibiotic topical creams. Due to the weak available evidence supporting the use of ciclosporin and intravenous immunoglobulins, this patient was managed with steroid use only. His rash initially worsened, but ultimately, he made a full recovery without any sequelae. The patient was reviewed in the dermatology clinic four weeks post-discharge, and he did not have any residual disease.
PubMed: 37809172
DOI: 10.7759/cureus.44812 -
PloS One 2022A subset of individuals with COVID-19 can suffer from a severe form of the disease requiring breathing support for respiratory failure and even death due to disease...
INTRODUCTION
A subset of individuals with COVID-19 can suffer from a severe form of the disease requiring breathing support for respiratory failure and even death due to disease complications. COVID-19 disease severity can be attributed to numerous factors, where several studies have associated changes in the expression of serum pro-inflammatory cytokines with disease severity. However, very few studies have associated the changes in expression of pro-inflammatory changes in the nasopharyngeal milieu with disease severity. Therefore, in the current study, we performed differential gene expression analysis of various pro-inflammatory cytokines in the nasopharyngeal milieu of mild & severe COVID-19 cases.
MATERIAL AND METHOD
For this retrospective, cross-sectional study, a total of 118 nasopharyngeal swab samples, previously collected from mild and severe (based on the WHO criteria) COVID-19 patients were used. A real-time qPCR was performed to determine the viral loads and also evaluate the mRNA expression of eight cytokines (IL-1, IL-2, IL-4, IL-6, IL-10, IFN-γ, TGF-β1, and TNF-α). Subsequently, an unpaired T-test was applied to compare the statistical difference in mean expression of viral loads and each cytokine between the mild and severe groups, while the Pearson correlation test was applied to establish a correlation between disease severity, viral load, and cytokines expression. Similarly, a multivariable logistic regression analysis was performed to assess the relationship between different variables from the data and disease severity.
RESULTS
Out of 118 samples, 71 were mild, while 47 were severe. The mean viral load between the mild and severe groups was comparable (mild group: 27.07± 5.22; severe group: 26.37 ±7.89). The mRNA expression of cytokines IL-2, IL-6, IFN- γ, and TNF-α was significantly different in the two groups (p<0.05), where the Log2 normalized expression of IL-2, IL-6, IFN- γ, and TNF-α was found to be 2.2-, 16-, 2.3-, and 1.73-fold less in the severe group as compared to the mild group. Furthermore, we also observed a significant positive correlation between all the cytokines in the severe group. The multivariate analysis showed a significant relationship between age, IL-6, and disease severity.
CONCLUSION
This decreased expression of certain cytokines (IL-2, IL-6, TNF-α, and IFN-γ) in the nasopharyngeal milieu may be considered early biomarkers for disease severity in COVID-19 patients.
Topics: Humans; Cytokines; Tumor Necrosis Factor-alpha; Interleukin-6; Interleukin-2; Retrospective Studies; Cross-Sectional Studies; COVID-19; Gene Expression; Nasopharynx; RNA, Messenger
PubMed: 36584119
DOI: 10.1371/journal.pone.0279270 -
AAPS PharmSciTech Jul 2022Diseases caused by upper respiratory tract (URT) and pulmonary infections have been a serious threat to human health for millennia and lack of targeted effective...
Diseases caused by upper respiratory tract (URT) and pulmonary infections have been a serious threat to human health for millennia and lack of targeted effective therapeutic techniques. In this study, two kinds of cyclodextrin particles with typical particle shapes of nanocubes and microbars were synthesized through a facile process. Subsequently, the particles were used as carriers for loading and stabilizing iodine and characterizations were performed to demonstrate the loading mechanism. Next-generation impactor (NGI) experiments showed that iodine-loaded microbars (I@microbars) had a deposition rate of 79.75% in URT, while iodine-loaded nanocubes (I@nanocubes) were delivered to the deep lungs with a fine particle fraction (FPF) of 46.30%. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) indicated that the iodine-loaded nanocubes and microbars had similar bactericidal effect to povidone iodine solution. Cell viability studies and extracellular pro-inflammatory factor (TNF-α, IL-1β, IL-6) evaluations demonstrate noncytotoxic effects of the blank carriers and anti-inflammatory effects of iodine-loaded samples. The irritation of the rat pharynx by I@microbars was evaluated for the behavioral observations, body weight changes, histopathological studies, and TNF-α, IL-1β, and IL-6 levels in pharyngeal tissues. The results showed that I@microbars had no irritation to rat pharyngeal tissues at therapeutic doses. In conclusion, the present study provides novel treatment of URT infections via supramolecular cyclodextrin carriers for URT local therapy with iodine loading by a solvent-free method, which enhances the stability and reduces the inherent irritation without inhibiting their antimicrobial effects. Two kinds of cyclodextrin particles with typical shapes of microbars and nanocubes were synthesized by a facile process. Subsequently, iodine was successfully loaded into the particles by gas-solid interaction. The iodine-loaded microbars showed air dynamics characteristics for inhalation delivery to the upper respiratory tract with little alveolar deposition in the lungs.
Topics: Administration, Inhalation; Animals; Cyclodextrins; Interleukin-6; Iodine; Particle Size; Pneumonia; Rats; Tumor Necrosis Factor-alpha
PubMed: 35804252
DOI: 10.1208/s12249-022-02277-x