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Age and Ageing Aug 2020Statins are widely prescribed in the treatment of hypercholesterolemia. While their efficacy in the secondary prevention of vascular events is proven, their safety...
Statins are widely prescribed in the treatment of hypercholesterolemia. While their efficacy in the secondary prevention of vascular events is proven, their safety profile in older patients with multiple co-morbidities and polypharmacy remains questionable. Although rare, antihydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy is a severe adverse effect of statins, manifesting as myalgias, proximal muscle weakness, muscle cell necrosis and rhabdomyolysis. We report an uncommon case of an autopsy-proven anti-HMGCR necrotising myopathy predominately affecting pharyngeal muscles in an older patient, leading to dysphagia, pneumonia and death within 3 weeks from onset. Clinicians should screen for dysphagia in any patient with suspected anti-HMGCR myopathy, order an anti-HMGCR antibody titre and consider prompt immunosupressive therapy.
Topics: Aged; Autoantibodies; Autoimmune Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Myositis; Pharyngeal Muscles
PubMed: 32147707
DOI: 10.1093/ageing/afaa038 -
Journal of Cellular and Molecular... Sep 2018The presence of bile is not an uncommon finding in acidic oesophageal and extra-oesophageal refluxate, possibly affecting the hypopharyngeal mucosa and leading to...
The presence of bile is not an uncommon finding in acidic oesophageal and extra-oesophageal refluxate, possibly affecting the hypopharyngeal mucosa and leading to neoplastic events. We recently demonstrated that acidic bile (pH ≤ 4.0) can induce NF-κB activation and oncogenic mRNA phenotype in normal hypopharyngeal cells and generate premalignant changes in treated hypopharyngeal mucosa. We hypothesize that curcumin, a dietary inhibitor of NF-κB, may effectively inhibit the acidic bile-induced cancer-related mRNA phenotype, in treated human hypopharyngeal primary cells (HHPC), supporting its potential preventive use in vivo. Luciferase assay, immunofluorescence, Western blot, qPCR and PCR microarray analysis were used to explore the effect of curcumin in HHPC exposed to bile (400 μmol/L) at acidic and neutral pH. Curcumin successfully inhibited the acidic bile-induced NF-κB signalling pathway (25% of analysed genes), and overexpression of NF-κB transcriptional factors, c-REL, RELA(p65), anti-apoptotic bcl-2, oncogenic TNF-α, EGFR, STAT3, WNT5A, ΔNp63 and cancer-related IL-6. Curcumin effectively reduced bile-induced bcl-2 overexpression at both acidic and neutral pH. Our novel findings suggest that, similar to pharmacologic NF-κB inhibitor, BAY 11-7082, curcumin can suppress acidic bile-induced oncogenic mRNA phenotype in hypopharyngeal cells, encouraging its future in vivo pre-clinical and clinical explorations in prevention of bile reflux-related pre-neoplastic events mediated by NF-κB.
Topics: Anticarcinogenic Agents; Bile; Bile Acids and Salts; Curcumin; Epithelial Cells; ErbB Receptors; Gene Expression Regulation; Humans; Hydrogen-Ion Concentration; Hypopharynx; Interleukin-6; NF-kappa B; Phenotype; Primary Cell Culture; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-rel; RNA, Messenger; STAT3 Transcription Factor; Signal Transduction; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Wnt-5a Protein
PubMed: 29911313
DOI: 10.1111/jcmm.13701 -
Annals of Palliative Medicine Jul 2021Necrotizing fasciitis (NF) is a rare, fulminant, lethal soft-tissue infection result in fascial necrosis, it is rarer in the head and neck area. Infection caused by...
Necrotizing fasciitis (NF) is a rare, fulminant, lethal soft-tissue infection result in fascial necrosis, it is rarer in the head and neck area. Infection caused by Klebsiella oxytoca is much less common. Therefore, we reported a case of NF in the maxillofacial region, neck and upper mediastinum caused by Klebsiella oxytoca as the main cause recently treated in our department. The patient is a middle-aged male with a 10-year history of diabetes with unstable insulin control. The main symptoms were pain on left side with dysphagia and fever and the situation was getting worse. The patient had limited ability to have mouth open and had hyperemia, swelling on the left pharynx, maxillofacial area, and upper left neck and skin tenderness, and all symptoms were getting worse quick. The CT mainly found out that left oropharyngeal wall, parotid gland area, bilateral submaxilla, left neck, and superior mediastinum are swelling with gas. The blood test result: leukocytes count 16.64×109/L, neutrophils percentage 85.8%; C-Pr 320 mg/L; urinary routine: urine glucose (+++++), ketone bodies (+++++); fasting glucose metabolism: glucose 21.33 mmol/L, glycosylated albumin 47.67%. Three incisions of facial and neck were performed to drain pus. Result of bacteria culture: Klebsiella oxytoca and Streptococcus constellatus During treatment of DKA and reduce patient glucose level, we also treated patient with neck and trachea incisions to drain pus and cleaned daily wound area and used different antibiotics according to the bacteria culture and CT results. And finally, the patient was cured and discharged from hospital. This case of NF was very rare not only the bacteria in this case but also the pathological changes related (involving the mediastinum). The report of his diagnosis and treatment can provide experience for future treatments.
Topics: Fasciitis, Necrotizing; Humans; Klebsiella oxytoca; Male; Mediastinum; Middle Aged; Neck; Streptococcus constellatus
PubMed: 33977729
DOI: 10.21037/apm-20-2427 -
Cancer Radiotherapie : Journal de La... Apr 2020Postradiation nasopharyngeal necrosis (PRNN) is a notorious complication after radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma (NPC). It is...
OBJECTIVE
Postradiation nasopharyngeal necrosis (PRNN) is a notorious complication after radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma (NPC). It is important for clinical doctors to realize this problem in order to cope with this severe clinical situation. The aim of our study was to assess the bacteriology of PRNN and to demonstrate the antimicrobial susceptibility pattern that should guide the clinicians towards more appropriate antibiotic use.
METHODS
Sixty-nine NPC patients with PRNN in our department between March 2013 and December 2017 were retrospectively enrolled. Pathogenic culture and drug sensitivity test were performed in these 69 NPC patients with PRNN. The infection rate of Pathogens and the sensitivity of the drugs were analyzed based on these results.
RESULTS
Sixty-nine NPC patients with PRNN were enrolled in our study. Pathogens were identified in 58 (84%) patients. Of the 58 patients, Staphylococcus aureus was isolated in 34 (58.6%) patients. And the second most common group of bacterial isolates was Pseudomonas aeruginosa. Antibiotic sensitivity showed that Levofloxacin was the highest (88.5%), followed by Ciprofloxacin (85.2%) and Gentamicin (80.3%). The only pathologic fungus was Candidaalbicans, about 6.8%. The positive rates of bacterial and fungal culture in PRNN patients were not significantly different from the patients' gender, age, stage, number of radiotherapy courses (P>0.05), but the cure rate was statistically higher in culture-negative patients in comparison with culture-positive patients (63.6% vs 20.7%, P=0.011).
CONCLUSION
Our results provide an overall picture of the microbiology and drug susceptibility patterns for NPC patients with PRNN and could help implement guidelines for more rational treatment and improve therapeutic outcome.
Topics: Adult; Aged; Anti-Bacterial Agents; Candida albicans; Ciprofloxacin; Female; Gentamicins; Humans; Levofloxacin; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Necrosis; Pseudomonas aeruginosa; Radiation Injuries; Retrospective Studies; Staphylococcus aureus; Treatment Outcome
PubMed: 32057645
DOI: 10.1016/j.canrad.2019.09.008 -
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 -
Frontiers in Immunology 2021The intercellular adhesion molecule-1 (ICAM-1), known as CD54, is a transmembrane cell surface glycoprotein that interacts with two integrins (i.e., LFA-1 and Mac-l)...
Molecular Characterization and Expression Analysis of Intercellular Adhesion Molecule-1 (ICAM-1) Genes in Rainbow Trout () in Response to Viral, Bacterial and Parasitic Challenge.
The intercellular adhesion molecule-1 (ICAM-1), known as CD54, is a transmembrane cell surface glycoprotein that interacts with two integrins (i.e., LFA-1 and Mac-l) important for trans-endothelial migration of leukocytes. The level of ICAM-1 expression is upregulated in response to some inflammatory stimulations, including pathogen infection and proinflammatory cytokines. Yet, to date, our knowledge regarding the functional role of ICAM-1 in teleost fish remains largely unknown. In this study, we cloned and characterized the sequence of ICAM-1 in rainbow trout () for the first time, which exhibited that the molecular features of ICAM-1 in fishes were relatively conserved compared with human ICAM-1. The transcriptional level of ICAM-1 was detected in 12 different tissues, and we found high expression of this gene in the head kidney, spleen, gills, skin, nose, and pharynx. Moreover, upon stimulation with infectious hematopoietic necrosis virus (IHNV), G (), and (Ich) in rainbow trout, the morphological changes were observed in the skin and gills, and enhanced expression of ICAM-1 mRNA was detected both in the systemic and mucosal tissues. These results indicate that ICAM-1 may be implicated in the mucosal immune responses to viral, bacterial, and parasitic infections in teleost fish, meaning that ICAM-1 emerges as a master regulator of mucosal immune responses against pathogen infections in teleost fish.
Topics: Animals; Ciliophora Infections; Fish Diseases; Fish Proteins; Flavobacteriaceae Infections; Flavobacterium; Gene Expression Regulation; Hymenostomatida; Infectious hematopoietic necrosis virus; Intercellular Adhesion Molecule-1; Oncorhynchus mykiss; Rhabdoviridae Infections
PubMed: 34489953
DOI: 10.3389/fimmu.2021.704224 -
EBioMedicine Mar 2020Human immunology research is often limited to peripheral blood. However, there are important differences between blood immune cells and their counterparts residing in...
BACKGROUND
Human immunology research is often limited to peripheral blood. However, there are important differences between blood immune cells and their counterparts residing in secondary lymphoid organs, such as in the case of germinal center (GC) T follicular helper (Tfh) cells and GC B cells.
METHODS
We developed a versatile ex vivo lymphoid organ culture platform that is based on human pharyngeal tonsils (adenoids) and allows for drug testing. We systematically phenotyped Tfh and GC B cell subsets in explant- and suspension cultures using multicolor flow cytometry and cytokine multiplex analysis.
FINDINGS
Phenotypic changes of certain ex vivo cultured immune cell subsets could be modulated by cytokine addition. Furthermore, we optimized an activation-induced marker assay to evaluate the response to T cell stimulation. We provide proof-of-concept that Tfh and GC B cells could be modulated in these cultures by different anti-inflammatory drugs in unstimulated states and upon activation with vaccine-derived antigens. For example, GC B cells were lost upon CD40L blockade, and clinically approved JAK inhibitors impacted Tfh and GC B cells, including down-regulation of their key transcription factor BCL6. BCL6 regulation was affected by IL-6 signaling in T cells and IL-4 in B cells, respectively. Furthermore, we demonstrated that JAK signaling and TNF signaling contributed to the stimulation-induced activation of tonsil-derived T cells.
INTERPRETATION
Our optimized methods, assays, and mechanistic findings can contribute to a better understanding of human GC responses. These insights may be relevant for improving autoimmune disease therapy and vaccination efficacy.
FUNDING
This work was supported by a project grant under the joint research cooperation agreement of LMU Munich, LMU University Hospital, and Sanofi-Aventis Deutschland GmbH, as well as by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - Emmy Noether Programme BA 5132/1-1 and BA 5132/1-2 (252623821), SFB 1054 Project B12 (210592381), and SFB 914 Project B03 (165054336).
Topics: Adenoids; Anti-Inflammatory Agents; B-Lymphocytes; Cells, Cultured; Child; Child, Preschool; Germinal Center; Humans; Immunophenotyping; Interleukins; Janus Kinases; Proto-Oncogene Proteins c-bcl-6; T Follicular Helper Cells; Tissue Culture Techniques; Tumor Necrosis Factor-alpha
PubMed: 32114393
DOI: 10.1016/j.ebiom.2020.102684 -
Molecular Medicine Reports Mar 2018Maternally expressed gene 3 (MEG3), a long noncoding RNA (lncRNA) has been dysregulated in various tumors. However, the expression level and functional role of MEG3 in...
Maternally expressed gene 3 (MEG3), a long noncoding RNA (lncRNA) has been dysregulated in various tumors. However, the expression level and functional role of MEG3 in the progression of respiratory syncytial virus (RSV) infection remains to be elucidated. The present study quantified the expression level of MEG3 in the nasopharyngeal (NPA) samples of RSV‑infected patients and in BEAS‑2B cells infected with RSV. The findings of the present study demonstrated that the expression level of lncRNA MEG3 was reduced in the NPA samples of RSV‑infected patients and in BEAS‑2B cells infected with RSV. In vitro transfection revealed increased mRNA expression levels of toll‑like receptor 4 (TLR4), tumor necrosis factor‑α (TNFα) and interleukin (IL)‑8 following RSV infection in BEAS‑2B cells. Additionally, ectopic expression of MEG3 reduced the expression level of TLR4, subsequently suppressing the mRNA expression levels of TNFα and IL‑8, indicating the protective role of MEG3 in the process of RSV infection. It is of note, that RSV infection‑induced p38 mitogen activated protein kinase (MAPK) and nuclear factor‑κB (NF‑κB) activation was partly abolished by overexpression of MEG3. In conclusion, to the best of our knowledge, the present study provided the first evidence that lncRNA MEG3 expression level was reduced in the NPA samples of patients with RSV infection and RSV‑infected cells. Additionally, it was demonstrated that MEG3 protected human airway epithelial cells from RSV infection, primarily by suppressing TLR4‑dependent p38 MAPK and NF‑κB signaling.
Topics: Bronchiolitis, Viral; Cell Line; Child; Child, Preschool; Epithelial Cells; Female; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Interleukin-8; Length of Stay; Male; NF-kappa B; Nasopharynx; RNA, Long Noncoding; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; p38 Mitogen-Activated Protein Kinases
PubMed: 29257348
DOI: 10.3892/mmr.2017.8303 -
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 -
Materia Socio-medica Feb 2016Acute intoxications with corrosive substances can cause severe chemical injuries of the upper gastrointestinal tract, most often located in the mouth, pharynx,...
INTRODUCTION
Acute intoxications with corrosive substances can cause severe chemical injuries of the upper gastrointestinal tract, most often located in the mouth, pharynx, esophagus, stomach and duodenum. If a patient survives the acute phase of intoxication, regenerative response may result in esophageal and/or gastric stenosis, and increased risk of esophageal and gastric cancer. Such intoxication may be fatal due to perforation or tracheal necrosis. Enteral nutrition is a nutritional method when nutritional substances are administered through specially designed tubing placed through the nose or percutaneously, directly into the GIT.
AIM
The aim of this study is to describe the methods of artificial nutrition in patients with acute corrosive intoxications and the importance of nutritional support in the treatment of these intoxications.
DISCUSSION
Nutrition in the treatment of acute corrosive intoxications is one of the most important therapeutic processes that largely contribute to faster recovery of the post-corrosive injuries of upper GIT, stabilization of biologic, immunologic and metabolic parameters, and reduction of length of stay in hospital Aim of the treatment of acute corrosive intoxications is to prevent perforation and progressive fibrosis, and esophageal and gastric stenosis. There are different and often conflicting positions, on the conservative treatment of acute corrosive intoxications in adults. Such treatment mainly consists of anti-secretory treatment, antibiotics and intensive hyper-alimentation, aiming to prevent late post-corrosive intoxications.
CONCLUSION
It is considered that nutritional support plays a major role in maintenance of metabolic processes and prevention of severe metabolic complications that could additionally aggravate the condition and impair the treatment.
PubMed: 27047272
DOI: 10.5455/msm.2016.28.66-70