Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 57
Filtrar
1.
Neuron ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34767770

RESUMO

The KCNQ family (KCNQ1-KCNQ5) of voltage-gated potassium channels plays critical roles in many physiological and pathological processes. It is known that the channel opening of all KCNQs relies on the signaling lipid molecule phosphatidylinositol 4,5-bisphosphate (PIP2). However, the molecular mechanism of PIP2 in modulating the opening of the four neuronal KCNQ channels (KCNQ2-KCNQ5), which are essential for regulating neuronal excitability, remains largely elusive. Here, we report the cryoelectron microscopy (cryo-EM) structures of human KCNQ4 determined in complex with the activator ML213 in the absence or presence of PIP2. Two PIP2 molecules are identified in the open-state structure of KCNQ4, which act as a bridge to couple the voltage-sensing domain (VSD) and pore domain (PD) of KCNQ4 leading to the channel opening. Our findings reveal the binding sites and activation mechanisms of ML213 and PIP2 for neuronal KCNQ channels, providing a framework for therapeutic intervention targeting on these important channels.

2.
Acta Otolaryngol ; 141(10): 915-920, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34633897

RESUMO

BACKGROUND: The success rate of stapedotomy in otosclerosis patients with cochlea involvement was unknown. AIMS/OBJECTIVES: To determine the difference of surgical outcomes and symptomatology in otosclerosis patients with or without cochlea involvement on CT. MATERIAL AND METHODS: 79 otosclerosis patients were included and grouped by HRCT, including cochlear-involved otosclerosis (C-group) or non-cochlear-involved otosclerosis (NC-group, control group). Patients were defined as NC-group in the presence of normal or solely fenestral involvement, or C-group if the hypodensities involve other parts of the labyrinthine bone Patients in the control group were collected at a 2:1 ratio to the C-group with similar follow-up times. Detailed complaints and surgical outcomes were compared between these groups. RESULTS: Chief complaints were similar in the C-group and NC-group. Although postoperative AC, BC, and ABG decreased significantly in both groups, the success rate was significantly higher in C-group regarding the postoperative ABG ≤10 dB. Furthermore, diffuse lesions may indicate a more severe disease and a poorer prognosis. CONCLUSIONS AND SIGNIFICANCE: Stapedotomy was effective for clinical otosclerosis. The surgical outcome was inferior favorable for cochlea involvement patients, especially for cases with widely involvement. There was no difference in chief complaints among patients with different CT degree of otosclerosis.

3.
Cell Rep ; 36(8): 109596, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34433060

RESUMO

Germline alterations of the NF2 gene cause neurofibromatosis type 2, a syndrome manifested with benign tumors, and Nf2 deletion in mice also results in slow tumorigenesis. As a regulator of the Hippo signaling pathway, NF2 induces LATS1/2 kinases and consequently represses YAP/TAZ. YAP/TAZ oncoproteins are also inhibited by motin family proteins (Motins). Here, we show that the Hippo signaling is fine-tuned by Motins in a NF2-dependent manner, in which NF2 recruits E3 ligase RNF146 to facilitate ubiquitination and subsequent degradation of Motins. In the absence of NF2, Motins robustly accumulate to restrict full activation of YAP/TAZ and prevent rapid tumorigenesis. Hence, NF2 deficiency not only activates YAP/TAZ by inhibiting LATS1/2 but also stabilizes Motins to keep YAP/TAZ activity in check. The upregulation of Motins upon NF2 deletion serves as a strategy for avoiding uncontrolled perturbation of the Hippo signaling and may contribute to the benign nature of most NF2-mutated tumors.

4.
Adv Drug Deliv Rev ; 176: 113891, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34324887

RESUMO

CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9) is a potent technology for gene-editing. Owing to its high specificity and efficiency, CRISPR/Cas9 is extensity used for human diseases treatment, especially for cancer, which involves multiple genetic alterations. Different concepts of cancer treatment by CRISPR/Cas9 are established. However, significant challenges remain for its clinical applications. The greatest challenge for CRISPR/Cas9 therapy is how to safely and efficiently deliver it to target sites in vivo. Nanotechnology has greatly contributed to cancer drug delivery. Here, we present the action mechanisms of CRISPR/Cas9, its application in cancer therapy and especially focus on the nanotechnology-based delivery of CRISPR/Cas9 for cancer gene editing and immunotherapy to pave the way for its clinical translation. We detail the difficult barriers for CRISIR/Cas9 delivery in vivo and discuss the relative solutions for encapsulation, target delivery, controlled release, cellular internalization, and endosomal escape.

5.
Mol Ther ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34174443

RESUMO

Myosin VI(MYO6) is an unconventional myosin that is vital for auditory and vestibular function. Pathogenic variants in the human MYO6 gene cause autosomal-dominant or -recessive forms of hearing loss. Effective treatments for Myo6 mutation causing hearing loss are limited. We studied whether adeno-associated virus (AAV)-PHP.eB vector-mediated in vivo delivery of Staphylococcus aureus Cas9 (SaCas9-KKH)-single-guide RNA (sgRNA) complexes could ameliorate hearing loss in a Myo6WT/C442Y mouse model that recapitulated the phenotypes of human patients. The in vivo editing efficiency of the AAV-SaCas9-KKH-Myo6-g2 system on Myo6C442Y is 4.05% on average in Myo6WT/C442Y mice, which was ∼17-fold greater than editing efficiency of Myo6WT alleles. Rescue of auditory function was observed up to 5 months post AAV-SaCas9-KKH-Myo6-g2 injection in Myo6WT/C442Y mice. Meanwhile, shorter latencies of auditory brainstem response (ABR) wave I, lower distortion product otoacoustic emission (DPOAE) thresholds, increased cell survival rates, more regular hair bundle morphology, and recovery of inward calcium levels were also observed in the AAV-SaCas9-KKH-Myo6-g2-treated ears compared to untreated ears. These findings provide further reference for in vivo genome editing as a therapeutic treatment for various semi-dominant forms of hearing loss and other semi-dominant diseases.

6.
Ear Hear ; 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34039936

RESUMO

Usher syndrome (USH) encompasses a group of clinically and genetically heterogenous disorders defined by the triad of sensorineural hearing loss (SNHL), vestibular dysfunction, and vision loss. USH is the most common cause of deaf blindness. USH is divided clinically into three subtypes-USH1, USH2, and USH3-based on symptom severity, progression, and age of onset. The underlying genetics of these USH forms are, however, significantly more complex, with over a dozen genes linked to the three primary clinical subtypes and other atypical USH phenotypes. Several of these genes are associated with other deaf-blindness syndromes that share significant clinical overlap with USH, pointing to the limits of a clinically based classification system. The genotype-phenotype relationships among USH forms also may vary significantly based on the location and type of mutation in the gene of interest. Understanding these genotype-phenotype relationships and associated natural disease histories is necessary for the successful development and application of gene-based therapies and precision medicine approaches to USH. Currently, the state of knowledge varies widely depending on the gene of interest. Recent studies utilizing next-generation sequencing technology have expanded the list of known pathogenic mutations in USH genes, identified new genes associated with USH-like phenotypes, and proposed algorithms to predict the phenotypic effects of specific categories of allelic variants. Further work is required to validate USH gene causality, and better define USH genotype-phenotype relationships and disease natural histories-particularly for rare mutations-to lay the groundwork for the future of USH treatment.

7.
Acta Otolaryngol ; 141(6): 603-607, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34028329

RESUMO

BACKGROUND: Although stapedotomy is effective for patients with clinical otosclerosis, the time of hearing stabilization has not yet been consistent. OBJECTIVE: To investigate the relationships between post-operative follow-up times, hearing outcomes, and threshold shift after stapedotomy. MATERIALS AND METHODS: Fifty-five patients with clinical otosclerosis that underwent stapedotomy were retrospectively studied. Pure tone audiometry tests were conducted within the first month (short-term) and within 1 year (mid-term) postoperatively. Data were analyzed for two rounds of audiometry tests at different postoperative follow-up times. RESULTS: Air conduction (AC) and bone conduction (BC) were significantly correlated with preoperative hearing levels (p<.01). AC, BC, and air bone gap (ABG) significantly improved at the short-term (p<.001) and continued to improve at the mid-term (p<.01). The success rate of surgery increased from 87% at short-term to 98% at mid-term. Less than 1/3 of cases encountered BC deterioration at short-term, whereas most improved at mid-term. CONCLUSIONS: Hearing results showed a trend of improvement between short-term and mid-term follow-ups after stapedotomy. AC, ABG, and success rate displayed significant improvement several months postoperatively. BC deterioration occurred in less than 30% of patients at short-term. The recovery of BC at 4 kHz was later than that of low frequencies.


Assuntos
Perda Auditiva/cirurgia , Otosclerose/cirurgia , Cirurgia do Estribo , Adulto , Audiometria de Tons Puros , Condução Óssea , Ossículos da Orelha/anatomia & histologia , Feminino , Seguimentos , Audição , Perda Auditiva/etiologia , Perda Auditiva Condutiva/etiologia , Perda Auditiva Condutiva/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Otosclerose/complicações , Otosclerose/patologia , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento
8.
Genome Biol ; 22(1): 86, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752742

RESUMO

BACKGROUND: Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection. RESULTS: The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV-CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV-CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV-CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz. CONCLUSIONS: These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.

9.
Eur Arch Otorhinolaryngol ; 278(3): 645-652, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32524207

RESUMO

PURPOSE: The aims of this article are: (1) is there an ideal incudostapedial joint (ISJ) angle after stapedotomy? (2) is there any difference between pre- and postoperative ISJ angle? and (3) what is the significance of the ISJ angle in postoperative hearing outcomes? METHODS: Forty six ears from 39 different adult patients (28 women and 11 men; 21 left and 25 right ears) with a mean age of 39 years with clinical otosclerosis who underwent stapedotomy between May 2017 and May 2019 were retrospectively registered, including seven bilateral surgery cases. ISJ angle and intravestibular depth of the stapes prosthesis were measured from multiple planar reconstruction-computed tomography images and the length of the prosthesis was measured during surgery. Relationships between the ISJ angle parameters and postoperative hearing outcomes and parameters of the prosthesis were analyzed. RESULTS: The mean ISJ angle was 93.3° ± 8.8° preoperatively and 101.9° ± 6.3° postoperatively, increasing by 8.6° during stapedotomy (p < 0.01). There were weak and negative correlations between ISJ angle changes and postoperative air conduction gains at frequencies ≤1 kHz and bone conduction gains at 0.5 kHz. When the postoperative ISJ angle changed more than 20°, the success rate of the procedure decreased to 0%. CONCLUSION: The stapedotomy operation increased the ISJ angle. The success of postoperative auditory outcomes had more to do with the ISJ angle change than the value of the angle itself, indicating there is no universal ideal ISJ angle that surgeons should aim for during stapedotomy.


Assuntos
Cirurgia do Estribo , Adulto , Condução Óssea , Feminino , Audição , Humanos , Bigorna/diagnóstico por imagem , Bigorna/cirurgia , Masculino , Prótese Ossicular , Otosclerose/diagnóstico por imagem , Otosclerose/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
10.
Laryngoscope ; 131(5): 1132-1137, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33030216

RESUMO

OBJECTIVES: To determine the clinical characteristics of papilloma involving the external auditory canal (PEAC) in a region of China. STUDY DESIGN: A retrospective study. METHODS: Demographics, manifestations, imaging results, histopathology, and treatment of 67 patients diagnosed with PEAC in a period of 6 years were analyzed at Shanghai Eye, Ear, Nose and Throat Hospital in China. RESULTS: PEAC were encountered in patients between the ages of 12 and 82 years (mean 53.8 years). It was more prevalent in men (82%) than in women (18%) (P < .05). The clinical presentation was usually a mass in EAC, aural fullness, and hearing loss. Otoscopic and radiological examination were used together for initial diagnosis and pretreatment planning. Unilateral involvement was more common than bilateral involvement (P < .05). The average time between onset of first symptom and surgical resection and/or biopsy was 6.5 months (range, 0.25-60 months). All patients underwent gross total resection. In 5 patients, (7.5%) carcinoma was detected in the specimen. Fifteen patients (22%) had recurrence; recurrent tumors were detected after an average period of 10 months after surgery (range, 4-24 months). CONCLUSION: PEAC is largely a benign lesion with a low risk of malignancy. Optimal management is via gross total resection. However, the risk of recurrence is high, which motivates a need for long-term monitoring. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1132-1137, 2021.


Assuntos
Meato Acústico Externo/patologia , Neoplasias da Orelha/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Procedimentos Cirúrgicos Otológicos/estatística & dados numéricos , Papiloma/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Meato Acústico Externo/cirurgia , Neoplasias da Orelha/patologia , Neoplasias da Orelha/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Procedimentos Cirúrgicos Otológicos/métodos , Papiloma/patologia , Papiloma/cirurgia , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
11.
Front Cell Dev Biol ; 8: 712, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32984303

RESUMO

Aminoglycoside-induced hair cell (HC) loss is one of the most important causes of hearing loss. After entering the inner ear, aminoglycosides induce the production of high levels of reactive oxygen species (ROS) that subsequently activate apoptosis in HCs. Citicoline, a nucleoside derivative, plays a therapeutic role in central nervous system injury and in neurodegenerative disease models, including addictive disorders, stroke, head trauma, and cognitive impairment in the elderly, and has been widely used in the clinic as an FDA approved drug. However, its effect on auditory HCs remains unknown. Here, we used HC-like HEI-OC-1 cells and whole organ explant cultured mouse cochleae to explore the effect of citicoline on aminoglycoside-induced HC damage. Consistent with previous reports, both ROS levels and apoptosis were significantly increased in neomycin-induced cochlear HCs and HEI-OC-1 cells compared to undamaged controls. Interestingly, we found that co-treatment with citicoline significantly protected against neomycin-induced HC loss in both HEI-OC-1 cells and whole organ explant cultured cochleae. Furthermore, we demonstrated that citicoline could significantly reduce neomycin-induced mitochondrial dysfunction and inhibit neomycin-induced ROS accumulation and subsequent apoptosis. Thus, we conclude that citicoline can protect against neomycin-induced HC loss by inhibiting ROS aggregation and thus preventing apoptosis in HCs, and this suggests that citicoline might serve as a potential therapeutic drug in the clinic to protect HCs.

12.
Mol Ther Methods Clin Dev ; 18: 511-519, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32953927

RESUMO

The aim of this study was to study an antimicrobial peptide (AMP), aurein 1.2, which substantially increased protein delivery directly into multiple mammalian inner-ear cell types in vivo. Different concentrations of aurein 1.2 with superpositively charged GFP (+36 GFP) protein fused with Cre recombinase were delivered to postnatal day 1-2 (P1-2) and adult cochleae of Cre reporter transgenic mice with various delivery methods. By cochleostomy at different concentrations of aurein 1.2-+36 GFP (1 µM, 5 µM, 22.5 µM, and 50 µM, respectively), the tdTomato (tdT) expression was observed in outer hair cells (OHCs; 20.77%, 23.02%, 76.36%, and 92.47%, respectively) and inner hair cells (IHCs; 14.90%, 44.50%, 89.59%, and 96.13%, respectively) in the cochlea. The optimal concentration was 22.5 µM with the highest transfection efficiency and the lowest cytotoxicity. Wide-spread tdT signals were detected in the cochlear-supporting cells, utricular-supporting cells, auditory nerve, and spiral ligament in neonatal and adult mice. Compared to cochleostomy, injection through the round window membrane (RWM) also produced highly efficient tdT+ labeled cells with less cell loss. In summary, the peptide aurein 1.2 fused with +36 GFP dramatically expanded the target cells with increased efficiency in direct protein delivery in the inner ear. Aurein 1.2-+36 GFP has the potential to be developed as protein-based therapy in regeneration and genome editing in the mammalian inner ear.

13.
Immunity ; 53(2): 456-470.e6, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32758419

RESUMO

Clinical evidence suggests that poor persistence of chimeric antigen receptor-T cells (CAR-T) in patients limits therapeutic efficacy. Here, we designed a CAR with recyclable capability to promote in vivo persistence and to sustain antitumor activity. We showed that the engagement of tumor antigens induced rapid ubiquitination of CARs, causing CAR downmodulation followed by lysosomal degradation. Blocking CAR ubiquitination by mutating all lysines in the CAR cytoplasmic domain (CARKR) markedly repressed CAR downmodulation by inhibiting lysosomal degradation while enhancing recycling of internalized CARs back to the cell surface. Upon encountering tumor antigens, CARKR-T cells ameliorated the loss of surface CARs, which promoted their long-term killing capacity. Moreover, CARKR-T cells containing 4-1BB signaling domains displayed elevated endosomal 4-1BB signaling that enhanced oxidative phosphorylation and promoted memory T cell differentiation, leading to superior persistence in vivo. Collectively, our study provides a straightforward strategy to optimize CAR-T antitumor efficacy by redirecting CAR trafficking.


Assuntos
Neoplasias/terapia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Linfócitos T/transplante , Animais , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Humanos , Memória Imunológica/imunologia , Imunoterapia Adotiva , Células Jurkat , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Mitocôndrias/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Linfócitos T/citologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Ubiquitinação , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Bioact Mater ; 5(4): 917-923, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32637754

RESUMO

Because of the unique features of spherical symmetry, angle-independency, good monodispersity, controllable components and morphologies, structural color particles (SCPs) have found great significances in various fields such as sensing, monitoring, biological assays, etc. Here, inspired by the melanosome-derived bright structural colors and the self-adhesivity of mussels, we present a kind of bioinspired SCPs assembled from polydopamine (PDA)-adhered multi-layer graphene oxide (GO) encapsulated silica nanoparticles (SNs). It is demonstrated that compared with traditional SCPs, the designed particles possess brighter and more vibrant structural colors, and no complicated modification is required during the functionalization process due to the abundant inherent functional groups of GO. The resultant SCPs are verified to be capable for direct hybridization chain reaction and multiplexed nucleic acid assays. These properties indicate the promising prospects of our designed SCPs.

15.
Front Public Health ; 8: 205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574296

RESUMO

The COVID-19 outbreak spread rapidly throughout the globe, with worldwide infections and deaths continuing to increase dramatically. To control disease spread and protect healthcare workers, accurate information is necessary. We searched PubMed and Google Scholar for studies published from December 2019 to March 31, 2020 with the terms "COVID-19," "2019-nCoV," "SARS-CoV-2," or "Novel Coronavirus Pneumonia." The main symptoms of COVID-19 are fever (83-98.6%), cough (59.4-82%), and fatigue (38.1-69.6%). However, only 43.8% of patients have fever early in the disease course, despite still being infectious. These patients may present to clinics lacking proper precautions, leading to nosocomial transmission, and infection of workers. Potential COVID-19 cases must be identified early to initiate proper triage and distinguish them quickly from similar infections. Early identification, accurate triage, and standardized personal protection protocols can reduce the risk of cross infection. Containing disease spread will require protecting healthcare workers.


Assuntos
COVID-19 , Tosse/etiologia , Febre/etiologia , Pessoal de Saúde/estatística & dados numéricos , COVID-19/diagnóstico , COVID-19/transmissão , Saúde Global , Humanos , Controle de Infecções , Medição de Risco , SARS-CoV-2
16.
Otolaryngol Head Neck Surg ; 163(4): 714-721, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32539586

RESUMO

OBJECTIVE: To evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in coronavirus disease 2019 (COVID-19) patients. STUDY DESIGN: Multicenter case series. SETTING: Five tertiary care hospitals (3 in China, 1 in France, 1 in Germany). SUBJECTS AND METHODS: In total, 394 polymerase chain reaction (PCR)-confirmed COVID-19-positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and visual analog scale (VAS) were used to quantify olfactory and gustatory dysfunction, respectively. All subjects at 1 hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n = 239), German (n = 39), and French (n = 116) cohorts was 32%, 69%, and 49%, respectively. The median age of included subjects was 39 years, 92 of 161 (57%) were male, and 10 of 161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10 of 90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. Forty-three percent (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of severe acute respiratory syndrome coronavirus 2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Diagnóstico Precoce , Transtornos do Olfato/etiologia , Pneumonia Viral/complicações , Olfato/fisiologia , Distúrbios do Paladar/etiologia , Adolescente , Adulto , COVID-19 , Criança , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , França/epidemiologia , Alemanha/epidemiologia , Humanos , Masculino , Transtornos do Olfato/epidemiologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Prevalência , Estudos Retrospectivos , SARS-CoV-2 , Distúrbios do Paladar/epidemiologia , Adulto Jovem
17.
medRxiv ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32511546

RESUMO

OBJECTIVE: Evaluate the prevalence and characteristics of olfactory or gustatory dysfunction in COVID-19 patients Study Design: Multicenter Case Series Setting: 5 tertiary care hospitals (3 in China, 1 in France, 1 in Germany) Subjects and Methods: 394 PCR confirmed COVID-19 positive patients were screened, and those with olfactory or gustatory dysfunction were included. Data including demographics, COVID-19 severity, patient outcome, and the incidence and degree of olfactory and/or gustatory dysfunction were collected and analyzed. The Questionnaire of Olfactory Disorders (QOD) and Visual Analogue Scale (VAS) were used to quantify olfactory and gustatory dysfunction respectively. All subjects at one hospital (Shanghai) without subjective olfactory complaints underwent objective testing. RESULTS: Of 394 screened subjects, 161 (41%) reported olfactory and/or gustatory dysfunction and were included. Incidence of olfactory and/or gustatory disorders in Chinese (n=239), German (n=39) and French (n=116) cohorts were 32%, 69%, and 49% 138 respectively. The median age of included subjects was 39 years old, 92/161 (57%) were male, and 10/161 (6%) were children. Of included subjects, 10% had only olfactory or gustatory symptoms, and 19% had olfactory and/or gustatory complaints prior to any other COVID-19 symptom. Of subjects with objective olfactory testing, 10/90 demonstrated abnormal chemosensory function despite reporting normal subjective olfaction. 43% (44/102) of subjects with follow-up showed symptomatic improvement in olfaction or gustation. CONCLUSIONS: Olfactory and/or gustatory disorders may represent early or isolated symptoms of SARS-CoV-2 infection. They may serve as a useful additional screening criterion, particularly for the identification of patients in the early stages of infection.

18.
Otolaryngol Head Neck Surg ; 163(1): 121-131, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32396445

RESUMO

Objective. To describe coronavirus disease 2019 (COVID-19) patient presentations requiring otolaryngology consultation and provide recommendations for protective measures based on the experience of ear, nose, and throat (ENT) departments in 4 Chinese hospitals during the COVID-19 pandemic. Study Design. Retrospective case series. Setting. Multicenter. Subjects and Methods. Twenty hospitalized COVID-19 patients requiring ENT consultation from 3 designated COVID-19 hospitals in Wuhan, Shanghai, and Shenzhen were identified. Data on demographics, comorbidities, COVID-19 symptoms and severity, consult reason, treatment, and personal protective equipment (PPE) use were collected and analyzed. Infection control strategies implemented for ENT outpatients and emergency room visits at the Eye and ENT Hospital of Fudan University were reported. Results. Median age was 63 years, 55% were male, and 95% were in severe or critical condition. Six tracheotomies were performed. Posttracheotomy outcomes were mixed (2 deaths, 2 patients comatose, all living patients still hospitalized). Other consults included epistaxis, pharyngitis, nasal congestion, hyposmia, rhinitis, otitis externa, dizziness, and tinnitus. At all hospitals, powered air-supply filter respirators (PAPRs) were used for tracheotomy or bleeding control. PAPR or N95-equivalent masks plus full protective clothing were used for other complaints. No inpatient ENT providers were infected. After implementation of infection control strategies for outpatient clinics, emergency visits, and surgeries, no providers were infected at the Eye and ENT Hospital of Fudan University. Conclusions and Relevance. COVID-19 patients require ENT consultation for many reasons, including tracheotomy. Otolaryngologists play an indispensable role in the treatment of COVID-19 patients but, due to their work, are at high risk of exposure. Appropriate protective strategies can prevent infection of otolaryngologists.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Otolaringologia/normas , Otorrinolaringopatias/terapia , Pandemias , Equipamento de Proteção Individual/normas , Pneumonia Viral/epidemiologia , Adulto , Idoso , COVID-19 , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/transmissão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Otorrinolaringopatias/complicações , Pneumonia Viral/complicações , Pneumonia Viral/transmissão , Estudos Retrospectivos , SARS-CoV-2
19.
Ear Nose Throat J ; : 145561320923823, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32352873

RESUMO

OBJECTIVE: Chronic suppurative otitis media (CSOM) is mostly caused by bacterial infection of the middle ear and antibiotics are generally used empirically, which may lead to the emergence of resistant bacterial strains. The objective of the study is to assess the bacteriological profile of and evaluate the antibiotic susceptibility of strains isolated in a tertiary care hospital in Shanghai, China. METHODS: This study included 289 individuals with clinical diagnosis of CSOM. Middle ear purulent discharge was obtained with sterile swabs and cultured for bacterial pathogens. The susceptibility of the isolated microorganisms to antibiotics was assessed by a microdilution method. RESULTS: Bacterial pathogens were found in 223 (77.2%) of the 289 cases. A total of 236 strains were isolated. Staphylococcus aureus was the commonest bacteria (44.9%) followed by Pseudomonas aeruginosa (16.9%) and coagulase-negative Staphylococcus (8.5%). There were 18.9% methicillin-resistant S aureus (MRSA) among the obtained S aureus organisms. Multidrug-resistant P aeruginosa was found in 4 patients, making up 10% of all detected P aeruginosa. Staphylococcus aureus showed highest susceptibility to vancomycin (100%), then gentamicin (98.1%) and rifampicin (97.2%) and was most resistant to penicillin (61.3%) and erythromycin (50%). All isolated P aeruginosa showed susceptibility to piperacillin, piperacillin/tazobactam, and meropenem. High degree of resistance in P aeruginosa was observed toward levofloxacin (42.5%), ciprofloxacin (40%), and ceftriaxone (30%). CONCLUSION: The high prevalence of MRSA and fluoroquinolone-resistant P aeruginosa indicated cephalosporins and fluoroquinolone as primary empirical antibiotic drugs in CSOM to be cautiously used. In order to reduce the incidence of resistant strains and promote effective usage of antibiotics, all aural discharges should be cultured to determine antibacterial susceptibility patterns before treatment.

20.
Otolaryngol Head Neck Surg ; 162(6): 809-810, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32286913

RESUMO

More than half of COVID-19 patients are afebrile early in the disease course, yet mildly ill or asymptomatic patients can still spread SARS-CoV-2 with high efficiency. Atypically presenting patients may be seen in noninfectious disease settings such as otolaryngology, which is a specialty prone to occupational exposure. Otolaryngologists have been infected with COVID-19 at higher rates than other specialties in China and other countries. Otolaryngology providers should maintain high clinical suspicion for mild and asymptomatic COVID-19 patients. Protective strategies should be implemented including preappointment screening, triaging, restriction of nonurgent visits and surgeries, telemedicine, and appropriate personal protective equipment use.


Assuntos
Doenças Assintomáticas/terapia , Infecções por Coronavirus/prevenção & controle , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Saúde do Trabalhador , Otolaringologia/organização & administração , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Doenças Assintomáticas/epidemiologia , COVID-19 , Controle de Doenças Transmissíveis/organização & administração , Gerenciamento Clínico , Feminino , Saúde Global , Pessoal de Saúde/estatística & dados numéricos , Humanos , Masculino , Otorrinolaringologistas/estatística & dados numéricos , Pandemias/estatística & dados numéricos , Precauções Universais/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...