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The Cochrane Database of Systematic... May 2022COVID-19 illness is highly variable, ranging from infection with no symptoms through to pneumonia and life-threatening consequences. Symptoms such as fever, cough, or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
COVID-19 illness is highly variable, ranging from infection with no symptoms through to pneumonia and life-threatening consequences. Symptoms such as fever, cough, or loss of sense of smell (anosmia) or taste (ageusia), can help flag early on if the disease is present. Such information could be used either to rule out COVID-19 disease, or to identify people who need to go for COVID-19 diagnostic tests. This is the second update of this review, which was first published in 2020.
OBJECTIVES
To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19.
SEARCH METHODS
We undertook electronic searches up to 10 June 2021 in the University of Bern living search database. In addition, we checked repositories of COVID-19 publications. We used artificial intelligence text analysis to conduct an initial classification of documents. We did not apply any language restrictions.
SELECTION CRITERIA
Studies were eligible if they included people with clinically suspected COVID-19, or recruited known cases with COVID-19 and also controls without COVID-19 from a single-gate cohort. Studies were eligible when they recruited people presenting to primary care or hospital outpatient settings. Studies that included people who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards.
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently selected all studies, at both title and abstract, and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and assessed risk of bias using the QUADAS-2 checklist, and resolved disagreements by discussion with a third review author. Analyses were restricted to prospective studies only. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic (ROC) space and in dumbbell plots. We estimated summary parameters using a bivariate random-effects meta-analysis whenever five or more primary prospective studies were available, and whenever heterogeneity across studies was deemed acceptable.
MAIN RESULTS
We identified 90 studies; for this update we focused on the results of 42 prospective studies with 52,608 participants. Prevalence of COVID-19 disease varied from 3.7% to 60.6% with a median of 27.4%. Thirty-five studies were set in emergency departments or outpatient test centres (46,878 participants), three in primary care settings (1230 participants), two in a mixed population of in- and outpatients in a paediatric hospital setting (493 participants), and two overlapping studies in nursing homes (4007 participants). The studies did not clearly distinguish mild COVID-19 disease from COVID-19 pneumonia, so we present the results for both conditions together. Twelve studies had a high risk of bias for selection of participants because they used a high level of preselection to decide whether reverse transcription polymerase chain reaction (RT-PCR) testing was needed, or because they enrolled a non-consecutive sample, or because they excluded individuals while they were part of the study base. We rated 36 of the 42 studies as high risk of bias for the index tests because there was little or no detail on how, by whom and when, the symptoms were measured. For most studies, eligibility for testing was dependent on the local case definition and testing criteria that were in effect at the time of the study, meaning most people who were included in studies had already been referred to health services based on the symptoms that we are evaluating in this review. The applicability of the results of this review iteration improved in comparison with the previous reviews. This version has more studies of people presenting to ambulatory settings, which is where the majority of assessments for COVID-19 take place. Only three studies presented any data on children separately, and only one focused specifically on older adults. We found data on 96 symptoms or combinations of signs and symptoms. Evidence on individual signs as diagnostic tests was rarely reported, so this review reports mainly on the diagnostic value of symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. RT-PCR was the most often used reference standard (40/42 studies). Only cough (11 studies) had a summary sensitivity above 50% (62.4%, 95% CI 50.6% to 72.9%)); its specificity was low (45.4%, 95% CI 33.5% to 57.9%)). Presence of fever had a sensitivity of 37.6% (95% CI 23.4% to 54.3%) and a specificity of 75.2% (95% CI 56.3% to 87.8%). The summary positive likelihood ratio of cough was 1.14 (95% CI 1.04 to 1.25) and that of fever 1.52 (95% CI 1.10 to 2.10). Sore throat had a summary positive likelihood ratio of 0.814 (95% CI 0.714 to 0.929), which means that its presence increases the probability of having an infectious disease other than COVID-19. Dyspnoea (12 studies) and fatigue (8 studies) had a sensitivity of 23.3% (95% CI 16.4% to 31.9%) and 40.2% (95% CI 19.4% to 65.1%) respectively. Their specificity was 75.7% (95% CI 65.2% to 83.9%) and 73.6% (95% CI 48.4% to 89.3%). The summary positive likelihood ratio of dyspnoea was 0.96 (95% CI 0.83 to 1.11) and that of fatigue 1.52 (95% CI 1.21 to 1.91), which means that the presence of fatigue slightly increases the probability of having COVID-19. Anosmia alone (7 studies), ageusia alone (5 studies), and anosmia or ageusia (6 studies) had summary sensitivities below 50% but summary specificities over 90%. Anosmia had a summary sensitivity of 26.4% (95% CI 13.8% to 44.6%) and a specificity of 94.2% (95% CI 90.6% to 96.5%). Ageusia had a summary sensitivity of 23.2% (95% CI 10.6% to 43.3%) and a specificity of 92.6% (95% CI 83.1% to 97.0%). Anosmia or ageusia had a summary sensitivity of 39.2% (95% CI 26.5% to 53.6%) and a specificity of 92.1% (95% CI 84.5% to 96.2%). The summary positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.55 (95% CI 3.46 to 5.97) and 4.99 (95% CI 3.22 to 7.75) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The summary positive likelihood ratio of ageusia alone was 3.14 (95% CI 1.79 to 5.51). Twenty-four studies assessed combinations of different signs and symptoms, mostly combining olfactory symptoms. By combining symptoms with other information such as contact or travel history, age, gender, and a local recent case detection rate, some multivariable prediction scores reached a sensitivity as high as 90%.
AUTHORS' CONCLUSIONS
Most individual symptoms included in this review have poor diagnostic accuracy. Neither absence nor presence of symptoms are accurate enough to rule in or rule out the disease. The presence of anosmia or ageusia may be useful as a red flag for the presence of COVID-19. The presence of cough also supports further testing. There is currently no evidence to support further testing with PCR in any individuals presenting only with upper respiratory symptoms such as sore throat, coryza or rhinorrhoea. Combinations of symptoms with other readily available information such as contact or travel history, or the local recent case detection rate may prove more useful and should be further investigated in an unselected population presenting to primary care or hospital outpatient settings. The diagnostic accuracy of symptoms for COVID-19 is moderate to low and any testing strategy using symptoms as selection mechanism will result in both large numbers of missed cases and large numbers of people requiring testing. Which one of these is minimised, is determined by the goal of COVID-19 testing strategies, that is, controlling the epidemic by isolating every possible case versus identifying those with clinically important disease so that they can be monitored or treated to optimise their prognosis. The former will require a testing strategy that uses very few symptoms as entry criterion for testing, the latter could focus on more specific symptoms such as fever and anosmia.
Topics: Aged; Ageusia; Anosmia; Artificial Intelligence; COVID-19; COVID-19 Testing; Child; Cough; Dyspnea; Fatigue; Fever; Hospitals; Humans; Outpatients; Pharyngitis; Primary Health Care; Prospective Studies; SARS-CoV-2; Sensitivity and Specificity
PubMed: 35593186
DOI: 10.1002/14651858.CD013665.pub3 -
Clinical Otolaryngology : Official... Jul 2022The aim of this study was to assess the effect of topical steroids on acute-onset olfactory dysfunction in patients infected with COVID-19. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The aim of this study was to assess the effect of topical steroids on acute-onset olfactory dysfunction in patients infected with COVID-19.
DESIGN AND SETTING
Systematic review and meta-analysis of cohort studies.
PARTICIPANTS
Patients infected with COVID-19.
MAIN OUTCOME MEASURES
PubMed, Embase, the Web of Science, SCOPUS, Cochrane database and Google Scholar were searched for articles up to September 2021. We analysed studies comparing the improvement of olfactory dysfunction between topical steroid treatment and control groups (placebo or no treatment). In addition, we performed a subgroup analysis by study type.
RESULTS
The improvement of olfactory score at 2 (standardised mean difference [SMD] = 0.7272, 95% confidence interval = [0.3851, 1.0692], p < .0001, I = 62.1%) and 4 weeks post-treatment (SMD = 1.0440 [0.6777, 1.4102], p < .0001, I = 61.2%) was statistically greater in the treatment than control group. However, there was no significant difference (odds ratio [OR] = 1.4345 [0.9525, 2.1604], p = .0842, I = 45.4%) in the incidence of fully recovery from anosmia/hyposmia between the treatment and control groups. In subgroup analysis, there were no significant differences in the improvement of olfactory score at 4 weeks post-treatment (OR = 0.6177 [0.1309, 1.1045] vs. 0.1720 [0.8002, 1.5438], p = .0761) or the incidence of full recovery from anosmia/hyposmia (OR = 1.8478 [0.6092, 5.6053] vs. 1.3784 [0.8872, 2.1414], p = .8038) between randomised and non-randomised controlled trials.
CONCLUSIONS
Although this meta-analysis found that topical steroids improved the acute-onset olfactory dysfunction caused by COVID-19, there was no difference in the rate of full olfactory recovery between treated and control patients.
Topics: Anosmia; COVID-19; Humans; Olfaction Disorders; Smell; Steroids
PubMed: 35352483
DOI: 10.1111/coa.13933 -
The Laryngoscope Jun 2022Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention.
METHODS
PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID-19 infection and OD, following preferred reporting items for systematic reviews and meta-analyses guidelines and a PROSPERO-registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random-effects meta-analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID-19-associated OD.
RESULTS
We included 7 case-control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID-19 infection and OD (63%, 95% CI = 0.38-0.82) was significantly higher than that in controls (4%, 95% CI = 0.01-0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID-19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes.
CONCLUSION
Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID-19 patients. Laryngoscope, 132:1260-1274, 2022.
Topics: Adolescent; Adult; COVID-19; Humans; Olfaction Disorders; Olfactory Bulb; Olfactory Mucosa; Smell
PubMed: 35318656
DOI: 10.1002/lary.30078 -
Reviews in Medical Virology Nov 2022Coronavirus disease 2019 (COVID-19) is a novel disease caused by a newly identified virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing diverse... (Review)
Review
Coronavirus disease 2019 (COVID-19) is a novel disease caused by a newly identified virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing diverse systemic manifestations. The oral cavity too is not spared and the symptoms appear either independently, concurrently, or sequentially. In view of the rising documented cases of oral lesions of COVID-19, this systematic review aims to assess the prevalence of oral manifestations in COVID-19 confirmed individuals. An extensive literature search was conducted in databases like Scopus, Pubmed/Medline, Livivo, Lilacs and Google Scholar and varied oral signs and symptoms were reported as per the PRISMA guidelines. Studies published in English language literature only were included and were subjected to the risk of bias using the Joana Briggs Institute Appraisal tools for prevalence studies, case series and case reports. In a two-phase selection, 34 studies were included: 21 observational, 3 case-series and 10 case reports. These observational studies included approximately 14,003 patients from 10 countries. In this review, we explored the most commonly encountered oral and dental manifestations in COVID-19 and identified that loss of taste acuity, xerostomia and anosmia were frequently reported. Elevated incidence of opportunistic infections like mucormycosis and aspergillosis were reported during the treatment due to prolonged intake of steroids. Immunosuppression and poor oral hygiene led to secondary manifestations like enanthematous lesions. However, it is not clear that oral signs and symptoms are due to COVID-19 infection itself or are the result of extensive treatment regimen followed [PROSPERO CRD42021258264].
Topics: Humans; COVID-19; SARS-CoV-2; Prevalence
PubMed: 35271738
DOI: 10.1002/rmv.2345 -
Chinese Medical Sciences Journal =... Mar 2022Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection. In anosmic patients, SARS-CoV-2 temporarily alters the signaling process in olfactory...
Background Anosmia is one of the symptoms in individuals with SARS-CoV-2 infection. In anosmic patients, SARS-CoV-2 temporarily alters the signaling process in olfactory nerve cells and olfactory bulb (OB), which eventually damages the structure of the olfactory epithelium, leading to a permanent disorder in the olfactory pathway that this damaged structure is showed in MRI imaging Methods Two investigators independently searched four databases consisting of PubMed, ProQuest, Scopus, and Web of Science for relevant records as of November 11, 2020 with no time, space, and language restrictions. Google Scholar was also searched for the related resources within the time limit of 2020. All the found articles were reviewed based on the PRISMA flow diagram. Qualitative studies, case reports, editorials, letters, and other non-original studies were excluded from this systematic analysis. Results Initial search yielded 434 records. After reviewing the titles and abstracts, we selected 74 articles; finally, 8 articles were depicted to be investigated and read in full text. The obtained results showed an increase in the width and volume of the olfactory cleft (OC), complete or partial destruction of OC, and complete occlusion of OC in COVID-19 patients. Deformation and degeneration as well as a subtle asymmetry were evident in the OBs. Computed tomography (CT), meganetic resonance imaging (MRI), and positron emission tomography (PET) were used to detect the outcomes of anosmia in these studies. Conclusions The changes in OC are greater than those in OB in patients with COVID-19, mainly due to the inflammatory and immune responses in OC. However, fewer changes in OB are due to neurological or vascular disorders. Topical steroid therapy and topical saline can be helpful.
PubMed: 35256044
DOI: 10.24920/003982 -
Journal of Nuclear Medicine : Official... Jul 2022Molecular imaging techniques such as PET and SPECT have been used to shed light on how coronavirus disease 2019 (COVID-19) affects the human brain. We provide a...
Molecular imaging techniques such as PET and SPECT have been used to shed light on how coronavirus disease 2019 (COVID-19) affects the human brain. We provide a systematic review that summarizes the current literature according to 5 predominant topics. First, a few case reports have suggested reversible cortical and subcortical metabolic alterations in rare cases with concomitant para- or postinfectious encephalitis. Second, imaging findings in single patients with the first manifestations of parkinsonism in the context of COVID-19 resemble those in neurodegenerative parkinsonism (loss of nigrostriatal integrity), but scarceness of data and a lack of follow-up preclude further etiologic conclusions (e.g., unmasking/hastening of neurodegeneration vs. infectious or parainfectious parkinsonism). Third, several case reports and a few systematic studies have addressed focal symptoms and lesions, most notably hyposmia. The results have been variable, although some studies found regional hypometabolism of regions related to olfaction (e.g., orbitofrontal and mesiotemporal). Fourth, a case series and systematic studies in inpatients with COVID-19-related encephalopathy (acute to subacute stage) consistently found a frontoparietal-dominant neocortical dysfunction (on imaging and clinically) that proved to be grossly reversible in most cases until 6 mo. Fifth, studies on post-COVID-19 syndrome have provided controversial results. In patients with a high level of self-reported complaints (e.g., fatigue, memory impairment, hyposmia, and dyspnea), some authors found extensive areas of limbic and subcortical hypometabolism, whereas others found no metabolic alterations on PET and only minor cognitive impairments (if any) on neuropsychologic assessment. Furthermore, we provide a critical appraisal of studies with regard to frequent methodologic issues and current pathophysiologic concepts. Finally, we devised possible applications of PET and SPECT in the clinical work-up of diagnostic questions related to COVID-19.
Topics: Anosmia; Brain; COVID-19; Coronavirus Infections; Humans; Molecular Imaging; Pandemics; Parkinsonian Disorders; Pneumonia, Viral; Post-Acute COVID-19 Syndrome
PubMed: 35177424
DOI: 10.2967/jnumed.121.263085 -
The Journal of Laryngology and Otology Jul 2022This meta-analysis provides a quantitative measure of the otorhinolaryngological manifestations of coronavirus disease 2019 in children. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This meta-analysis provides a quantitative measure of the otorhinolaryngological manifestations of coronavirus disease 2019 in children.
METHODS
A structured literature review was carried out using PubMed, Embase and Cochrane Central, employing pertinent search terms. The statistical analysis was performed using Stata version 14.2 software, and the analysed data were expressed as the pooled prevalence of the symptoms with 95 per cent confidence intervals.
RESULTS
The commonest symptoms noted were cough (38 per cent (95 per cent confidence interval = 33-42; I = 97.5 per cent)), sore throat (12 per cent (95 per cent confidence interval =10-14; I = 93.7 per cent)), and nasal discharge (15 per cent (95 per cent confidence interval = 12-19; I = 96.9 per cent)). Anosmia and taste disturbances showed a pooled prevalence of 8 per cent each. Hearing loss, vertigo and hoarseness were rarely reported.
CONCLUSION
Cough, sore throat and nasal discharge were the commonest otorhinolaryngological symptoms in paediatric patients with coronavirus disease 2019. Compared with adults, anosmia and taste disturbances were infrequently reported in children.
Topics: Adult; Anosmia; COVID-19; Child; Cough; Humans; Pharyngitis
PubMed: 35172911
DOI: 10.1017/S0022215122000536 -
International Journal of Preventive... 2021Evidence showed that partial or complete loss of smell and taste might be a possible primary symptom of the 2019 novel coronavirus (COVID-19). This study aimed to... (Review)
Review
BACKGROUND
Evidence showed that partial or complete loss of smell and taste might be a possible primary symptom of the 2019 novel coronavirus (COVID-19). This study aimed to systematically review and pool all available evidence on the olfactory and gustatory dysfunction in COVID-19 patients.
METHODS
In this systematic review, a comprehensive search was carried out systematically through e-databases including PubMed, EMBASE, Scopus, and Web of Science (WoS); that was limited to English-language studies published from 2019 up to 6 May 2020. Afterward, all studies reported the taste and smell dysfunction in the COVID-19 patients were included. The quality of the studies was assessed by the Mixed Methods Appraisal Tool (MMAT). The pooled prevalence of olfactory and gustatory dysfunction was estimated using the random effects meta-analysis method.
RESULTS
Among 28 eligible included studies in this systematic review, finally, 22 studies met the eligibility criteria and were included in the meta-analysis. According to the random effect meta-analysis, the global pooled prevalence (95% confidence interval) of any olfactory dysfunction, anosmia, and hyposmia was 55% (40%-70%), 40% (22%-57%), and 40% (20%-61%) respectively. The pooled estimated prevalence of any gustatory dysfunction, ageusia, and dysgeusia was 41% (23%-59%), 31% (3%-59%), and 34% (19%-48%) respectively.
CONCLUSIONS
Olfactory and gustatory dysfunction is prevalent among COVID-19 patients. Therefore, olfactory and gustatory dysfunction seems to be part of important symptoms and notify for the diagnosis of COVID-19, especially in the early phase of the infection.
PubMed: 35070203
DOI: 10.4103/ijpvm.IJPVM_484_20 -
World Neurosurgery Apr 2022Olfactory disturbance is a common complication that occurs following the surgical resection of olfactory groove meningiomas (OGMs). There is little evidence on the best... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Olfactory disturbance is a common complication that occurs following the surgical resection of olfactory groove meningiomas (OGMs). There is little evidence on the best transcranial approach that minimizes rates of postoperative olfactory disturbance. The objective of this systematic review and meta-analysis is to compare smell outcomes after OGM resection in unilateral versus bilateral transcranial approaches.
METHODS
A systematic review of the literature and meta-analysis was conducted using PUBMED, SCOPUS, and EMBASE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary endpoint was incidence of new olfactory disturbance defined as anosmia or hyposmia, or both. Patients were classified as undergoing either a unilateral or bilateral approach. Data on presence of new postoperative olfactory deficits were used to generate standardized mean differences and 95% confidence intervals.
RESULTS
Ten studies met the inclusion criteria for quantitative analysis, comprising 342 patients. A total of 216 patients underwent unilateral approaches while 126 underwent resection via bilateral approach. In the unilateral approach cohort, 17.1% experienced new postoperative olfactory disturbance following resection, compared with 19.2% of patients in the bilateral approach cohort. Forest plot did not reveal any significant difference in the incidence of new olfactory disturbance following either unilateral or bilateral approaches.
CONCLUSIONS
Our data suggest that there is no significant difference between the investigated transcranial approaches and postoperative olfactory disturbances. Accordingly, our study suggests that further investigation with introduced experimental control could provide more insight into the capabilities and drawbacks of each route in relation to olfactory outcomes.
Topics: Craniotomy; Humans; Meningeal Neoplasms; Meningioma; Neurosurgical Procedures; Smell; Treatment Outcome
PubMed: 35033688
DOI: 10.1016/j.wneu.2022.01.034 -
International Forum of Allergy &... Aug 2022Several studies have described techniques aimed at mitigating olfactory dysfunction after nasoseptal flap (NSF) harvest for endoscopic skull base surgery (ESBS). No... (Review)
Review
BACKGROUND
Several studies have described techniques aimed at mitigating olfactory dysfunction after nasoseptal flap (NSF) harvest for endoscopic skull base surgery (ESBS). No consensus exists as to whether popular methods including using cold steel (CS) versus electrocautery (EC) or septal olfactory strip (SOS) preservation offer an advantage. This systematic review was performed to examine the impact of these two technical variations of NSF harvest on postoperative olfactory outcomes.
METHODS
Following PRISMA guidelines, PubMed, Scopus, and Web of Science were searched for articles reporting olfactory outcomes in ESBS cases employing an NSF. Original articles focusing on technique variations of the NSF and reporting at least one objective olfactory measure were included.
RESULTS
Nine studies comprising 610 patients were included. Various, olfactory testing outcomes were reported, and postoperative follow-up ranged from 6 weeks to 12 months. Three studies, including a randomized controlled trial, compared the use of CS and EC for the superior incision of the NSF. No significant difference was found in objective olfactory function (p > 0.05) when comparing these techniques. Five studies comprising 504 patients reported results from SOS-sparing. SOS-sparing technique in NSF harvest demonstrated smell preservation in the postoperative setting when compared with preoperative measures (p > 0.05); however, no direct comparison to non-SOS-sparing techniques was made.
CONCLUSION
The use of CS as opposed to EC for the superior NSF incision does not appear to confer an advantage in preserving postoperative olfactory function (grade B evidence). SOS preservation may be associated with better olfactory outcomes in NSF harvest (grade C evidence).
Topics: Endoscopy; Humans; Postoperative Complications; Randomized Controlled Trials as Topic; Plastic Surgery Procedures; Retrospective Studies; Skull Base; Smell; Steel; Surgical Flaps
PubMed: 34910852
DOI: 10.1002/alr.22945