COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the newly developed worldwide outbreak of coronavirus disease with a high rate of mortality especially among elderly and multiple co-morbid personnel. Asymptomatic COVID-19-infected patients are a well-known source of transmission of infection. The risk of exposure to respiratory secretions and/or feces is hardly avoidable during the endoscopic procedure; also, the aerosol and droplets take up to an hour disperse, so they remain a risk to staff and other patients after they leave the room; therefore, strict infectious precautions should be taken by all health care workers to limit the virus spread.We present an endoscopic trial of duodenal stent insertion in non-operable gastric carcinoma that is proven 2 days later to be a COVID-19-positive case. Fortunately, no one of the health care workers that came in contact with the case becomes infected owing to the proper infection control measures.We recommended that the endoscopy examination and procedures should be strictly limited to urgent cases to minimize the risk of virus infection among health care workers. On 12 December 2019, a severe respiratory disease was recently reported in Wuhan, known as COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for the worldwide outbreak pandemic of coronavirus disease . Due to We report a case of a 40-year-old male patient, recently discovered with non-operable obstructing gastric cancer infiltrating the duodenum subjected to palliative endoscopic duodenal stenting, who proved to have a confirmed COVID-19 infection latterly. We aimed to emphasize the importance of prophylaxis measures during endoscopic procedures in the prevention of COVID-19 infection.On 9 March 2020, a 40-year-old male patient complained of obstructive jaundice, vomiting, dyspepsia, and weight loss of 15 kg in the last 2 months together with a mild sore throat, but there were no fever, dyspnea, cough, or any other respiratory symptoms. The patient was not known to have diabetes, hypertension, or any other medical condition. His diagnostic upper endoscopy showed a mass in the body extending to the antrum; multiple biopsies were taken for the histopathological examination which revealed a case of moderately differentiated adenocarcinoma (T3N1M0). CT scan of the abdomen was done and revealed an obstruction to the common hepatic duct (CHD) by diffuse lymphatic permeation, rather than definite soft tissue lesions, causing dilatation of the RT and LT hepatic ducts and IHBR together with malignant duodenal infiltration causing a picture of gastric outlet obstruction , rapidly progressive dyspnea, hypotension, and disturbance in the conscious level, upon which he was admitted to the ICU with the diagnosis of septic shock secondary to a chest infection. On admission to ICU, the patient has a disturbed conscious level GCS was 12 /15) with no lateralizing signs; chest examination revealed bilateral diminished air entry more to the left lung. Central venous catheter was inserted, resuscitation by IV fluids failed to achieve mean BP more than 65 mmHg so vasopressin therapy in the form of norepinephrine was started. Chest X-ray was done on day 1 of ICU admission which revealed bilateral ground-glass opacities more at the left lung  during the examination, and by restricting the endoscopic examination and procedures to the emergency cases only; however, there is still controversy between different societies regarding urgent procedures, postponement of non-urgent examinations, prescreening of patients, training for PPE use (to wear and to remove), contact patients 14 days after examination, and self-surveillance by HCW. It should be taken into consideration that the potential or confirmed cancer cases which are difficult to be deferred should be reviewed on a case-by-case basis.


Background and objectivesA flare-up in coronavirus disease 2019 (COVID-19) cases threatens the health of people, and though there is no proven pharmacological treatment, many analytical studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of severe COVID-19 and that the anti-IL-6 biologic agent tocilizumab may be beneficial. This is a critical review of studies aiming to assess the safety and efficacy of tocilizumab as compared to the standard regimen in patients with COVID-19.Materials and methodsOnline databases (PubMed and Cochrane) were searched until June 29, 2020, for original articles investigating the immunological response in COVID-19 and its treatment with tocilizumab. Data on multiple baseline characteristics and pre-specified endpoints were extracted and pooled using a random effect model. We used Review Manager version 5.3  and Stata 11.0  for all analyses. Risk ratios (RR) and the weighted mean difference (WMD) with the corresponding 95% confidence interval (CI) were calculated.Results2=76%), as was the need for artificial invasive ventilation  as compared to the control group. No significant differences were observed between tocilizumab and control group in intensive care unit admissions  and risks of post-drug infection . In terms of efficacy outcome, improved oxygen saturation  was reported to be markedly significant in tocilizumab patients when compared with the standard care group.From a total of 1,246 identified articles, 13 studies were included after duplicate removal and narrowing based on title and abstract. Of the 13 included studies, seven case-control studies were shortlisted for meta-analysis (quantitative) and six-single arm studies were used in the discussion . These studies had 766 patients (351 in the tocilizumab arm and 414 in the control arm). Their pooled analysis demonstrated that mortality was significantly lower in the tocilizumab group (RR=0.56 ; p=0.02; IConclusionsOur results based on pooled studies show tocilizumab to be safe and efficacious in reducing mortality among critically ill COVID-19 patients. However, due to the limited number of observational studies, the positive findings should be viewed cautiously and warrant further investigation. An exponential increase in the number of patients infected by severe acute respiratory syndrome-related coronavirus SARS-CoV-2), as well as the rapidly changing disease profile of coronavirus disease 2019 (COVID-19), has been a life-threatening and public health emergency [, as wellAlthough its pathogenesis is still vague, laboratory findings of patients suffering from severe disease show a cytokine storm, involving a considerable release of pro-inflammatory cytokines, among which Interleukin-6 (IL-6) plays a cardinal role . TocilizStudies carried out to evaluate the adequacy of tocilizumab so far have yielded different results. Some observational studies showed it to be beneficial, which led to its use in some countries and prompted further research; however, a recent randomized controlled trial (RCT), COVACTA , suggested no evidence of its benefit in COVID-19 [This meta-analysis was conducted according to the guidelines set by Preferred Reporting Items for Systemic Review and Meta-Analysis (PRISMA) and Cochrane guidelines -8.Search strategyA systematic literature search was conducted up till June 29, 2020, on the PubMed and Cochrane CENTRAL databases with the following subject keywords and their MeSH terms: ((COVID-19 OR Coronavirus OR SARS-coV-2) AND (Tocilizumab OR IL-6 antagonists OR IL-6 Inhibitors).Clinicaltrials.gov were searched for any studies that had not yet been published but had reported their results online. There was no language barrier, as all the studies retrieved in the search were in the English language. Two reviewers independently screened the search results. A third reviewer was consulted in case of discrepancies. Duplicates were removed and studies were initially shortlisted based on title and abstract, after which the full text was assessed for eligibility. References of the selected studies were also reviewed thoroughly to prevent any risk of selection bias.Google Scholar and Inclusion and exclusion criteriaObservational studies, including adults ≥18 years with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection in which the efficacy of tocilizumab added to standard therapy and standard therapy alone, were compared. Additionally, studies that had published full-text in the English language were considered. Only articles were excluded if they were reviews, editorials, or case reports. All identified studies were imported in EndNote Reference Library version X4  for the removal of duplicates.Data extractionData extraction of the relevant studies included the first author, year of publication, type of study, study follow-up time, total number of COVID-19 positive patients, and patients who received tocilizumab. From the obtained relevant studies, the baseline characteristics  and comorbidities  of patients in the two groups were also extracted. We accepted the study investigator’s definition for all safety and efficacy outcomes. The outcomes extracted are mentioned below.Safety outcomesSafety outcomes included mortality, ICU admission, risk of infection , need for mechanical ventilation, and serious adverse events.Efficacy outcomeImproved oxygen saturation was considered an efficacy outcome.Assessment of risk of biasQuality assessment of all the observational studies was done using the Newcastle-Ottawa reference scale .Statistical analysis2 statistic was used to evaluate heterogeneity, and the value of 25%-50% as mild, 50%-75% as moderate, and >75% was considered significant heterogeneity. A p-value of ≤0.05 was considered significant.Statistical analysis was done only for comparative studies using Review Manager version 5.3  and Stata 11.0 . Relative risks (RR) with 95% confidence intervals (CIs) were calculated using raw study data and were pooled using a random-effects model for dichotomous data. Due to the lack of adjusted outcome measures, baseline differences were assessed between the tocilizumab and control group patients in this study to identify potential confounding factors. Funnel plots for all outcomes were visualized and Begg's test was performed to assess publication bias. Potential causes of heterogeneity were explored by carrying out a subgroup analysis according to the use of corticosteroids analyses. The Higgins I A total of 1,246 articles were identified initially from the literature search, 1,231 from database searches and 15 from other sources such as references of relevant studies. Finally, 13 retrospective observational studies were found, amongst which seven were comparative -16 and sQuality assessment and publication biasThe quality assessment of studies using the New Castle Ottawa scale depicted a significantly low risk of bias in all the included case-control studies Table . The funBaseline characteristicsThe seven studies included 766 patients (351 in the tocilizumab arm and 414 in the control arm). The baseline characteristics and comorbidities of the comparative studies are given in Table Assessment of baseline differencesWhen baseline characteristics were pooled, we found significantly more male patients  and less diabetic patients  in the tocilizumab group. All the remaining characteristics were insignificant between both the intervention groups. Differences in key baseline characteristics between the tocilizumab group and the control group are represented in Table 5, 0.99; Safety outcomes2=76%) as compared to the control group, and no publication bias was found for the mortality outcome (p=0.20). Also, there was a significant decrease in patients needing post-therapy mechanical ventilation  in the tocilizumab group versus the control group. Yet, no significant differences were observed between the two groups in terms of ICU admissions , risk of post-drug infection  and serious adverse events . The forest plots for all the above-mentioned outcomes are displayed in Figure The pooled analysis of the patients receiving tocilizumab showed a significantly lower risk of mortality  was reported to be markedly significant in tocilizumab patients when compared with the standard care group as shown in Figure However, in terms of efficacy outcome, improved oxygen saturation . The details of other subgroup analyses are given in Table Subgroup analysis was performed to check whether the administration of corticosteroids in addition to tocilizumab and standard care influenced the results produced, and no significant difference was found in any safety and efficacy outcome among the subgroups except that infection was markedly reduced in those patients who were given corticosteroids  in the development of ARDS and lung failure -26. A meThe baseline characteristics and outcomes of six single-arm, observational studies investigating the safety of tocilizumab therapy in COVID-19 patients are shown in Table The meta-analysis suggests a significantly lower risk of mortality among the patients who received tocilizumab therapy along with standard therapy compared to those receiving standard therapy alone. This finding is consistent with the findings of most comparative observational studies, including those by Klopfenstein et al. and Capra et al. -11. In cConsistent with the results of the single-arm observational studies, this meta-analysis also demonstrated that a significantly lower number of patients requiring mechanical ventilation following tocilizumab therapy and a significant improvement in their blood oxygen saturation -5,26. ThTocilizumab is known to pose an increased risk of secondary bacterial/fungal infections due to its immunosuppressive mode of action. However, the pooling of the results demonstrated no significant difference in infections between the two groups. One plausible explanation may be the lower rate of intubation and mechanical ventilation in these patients, eliminating risk from infection-causing procedures. Interestingly, scientists in favor of tocilizumab suggest that the desquamation of alveolar cells, hyaline membrane formation, and pulmonary edema following the hyper-inflammatory state make the lungs more vulnerable to secondary infections, and hence tocilizumab has a protective action . Also, iPatients were administered corticosteroid therapy as part of the standard regimen in five of the seven cohorts. Corticosteroids have a potent anti-inflammatory effect . The posLimitationsThere are several limitations that this meta-analysis attempts to overcome, including the limited sample sizes, non-homogenous sample population, and short duration of studies. To minimize inter-study heterogeneity, the baseline characteristics of both cohorts were adjusted. However, the lack of a uniform standard protocol for treatment and no clear guidelines on the dosing and administration of tocilizumab generate a confounding bias. Moreover, the populations differed in disease severity and the relative time of treatment during the course of the disease.Tocilizumab appears to improve mortality and oxygen saturation as compared to controls upon pooling of the observational studies; however, the COVACTA trial showed no mortality benefit . The obsThis meta-analysis shows that therapy with tocilizumab lowers the mortality rate and risk of artificial ventilation in COVID-19 patients and improves their oxygen saturation levels. While it has no role in reducing ICU admissions, it does not pose a serious risk of infections and other adverse events. Furthermore, concomitant corticosteroid therapy seems to lower the risk of infections. Similarly, the six single-arm studies show a lower mortality rate with tocilizumab therapy. Tocilizumab is a promising agent to attenuate inflammation and cytokine release, which is the underlying pathophysiology of several COVID-19 cases. However, the poor design and various limitations of the studies render them ineffective in gauging the full extent of its safety and efficacy and thus warrant further research into the use of tocilizumab.


Ependymoma (EPN) is a rare primary tumor of the central nervous system (CNS) that affects both children and adults. Despite the definition and classification of distinct molecular subgroups, there remains a group of EPNs with a balanced genome, which makes it difficult to predict a prognosis of patients with EPN. The role of miRNA-mRNA network on EPN is still poorly understood. We assessed the involvement of miRNA-mRNA pairs in EPN by applying a weighted co-expression network analysis (WGCNA) approach. Using whole genome expression profile analysis followed by functional enrichment, we detected hub genes involved in active proliferation and DNA replication of nerve cells. Key genes including CYP11B1, KRT33B, RUNX1T1, SIK1, MAP3K4, MLANA, and SFRP5 identified in co-expression networks were regulated by miR-15a and miR-24-1. These seven miRNA-mRNA pairs were considered to influence not only pathways in cancer and tumor suppression process, but also MAPK, NF-kappaB, and WNT signaling pathways which were associated with tumorigenesis and development. This study provides a novel insight into potential diagnostic biomarkers of EPN and may have value in choosing therapeutic targets with clinical utility. Ependymomas (EPN) are rare neuroepithelial primary tumors of the brain and spinal cord that occurs in both children and adults. EPNs in childhood arise most often within the posterior fossa (PF) than supratentorial brain (ST), while spinal cord EPNs occur more frequently in adulthood. These neoplasms are the third most common central nervous system (CNS) tumors in children, accounting for 6–12% of brain tumors in childhood, while making up 1.8% of all primary tumors of the CNS , 2016. TThe microRNAs (miRNAs), small non-coding RNAs of approximately 22 nucleotides, fine-tune gene expression by binding to the 3′-UTR of the target mRNAs post-transcriptionally, causing gene silencing . PreviouIn silico technology greatly improves the efficiency of our research on molecular mechanisms and biological functions  can find co-expressed genes by calculating gene connectivity, and identify candidate biomarkers from a large number of gene sets rather than a small number of differentially expressed gene sets . It is aunctions . Theoretunctions . The larunctions . In thisGSE21687 (The paired mRNA expression and miRNA profiles of 64 ependymoma patients were downloaded from NCBI Gene Expression Omnibus (GEO) with accession number GSE21687 . The 64 GSE21687 . FinallyThe workflow of the miRNA and mRNA co-expression network analysis was shown in Screening hub genes and detecting co-expression of miRNA-mRNA pairs were performed by WGCNA, which is an R package for analyzing a weighted correlation network . Appropr1 and the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were downloaded from the KEGG database2. Hypergeometric distribution test  methods with a cutoff FDR < 0.05. Significantly enriched entries in all modules were sorted in ascending order by FDR value.We performed functional enrichment analysis on clustered genes in each module to detect the biological function of co-expressed hub genes. Gene Ontology (GO) terms included three parts: Biological Progress (BP), Molecular Function (MF), and Cell Component (CC). These were downloaded from the Gene Ontology databaseion test  was applWe used a hypergeometric test to identify the miRNA-enriched modules. For each module, we counted the number of members (genes and miRNAs) and the number of miRNAs and compared them with the number of all genes and miRNAs and the number of all miRNAs. Based on these numbers, we can calculate the statistical significance of miRNA enrichment in this module using a hypergeometric test. The modules with FDR < 0.05 were considered as miRNA-enriched modules.3, PicTar4, TarBase5, MirTarget6, miRBase7, and TargetScan8 databases to detect target genes of miRNAs. All records in the databases were retained and merged into a set of predicted miRNA target genes.Interested miRNAs were searched against miRanda2 meant how well the liner regression model fit for the association between degree and the log of the number of nodes with the corresponding degree. In scale-free network, the degree and the number of nodes with a corresponding degree has a power law relationship. Therefore, the degree and the log of the number of nodes with a corresponding degree has a linear relationship and the R2 of the linear regression model can be used to check how well the network fits the scale freeness. When soft-thresholding power was set to be five, the R2 was 0.967. A total of 38 modules were detected in this network and their relationship was shown in a cluster dendrogram , in which less than 0.05 were retained and sorted into ascending order. It was found that genes in the red module significantly enriched in cell cycle and DNA replication pathway , which were important processes during cell proliferation. The synaptic vesicle cycle pathway and glutamatergic synapse pathway was remarkably enriched in turquoise module , reflecting genes in such modules played important roles in the nervous system.To investigate the functions of classified modules, we used a hypergeometric distribution test to analyze KEGG and GO enrichment on each clustered module . After F–61), nucleic acid binding , and synapse part , which indicated that these co-expressed gene hubs were closely related to proliferation and genome replication of nerve cells.The Gene Ontology (GO) enrichment analysis was performed on all modules from three aspects: biological process, molecular function, and cellular component . Top terBeside the KEGG and GO functional annotations, we enriched the modules with reported multi-omics ependymoma signatures: the 51 gene expression signatures of ependymoma survival from Supplementary Table 6 of We compared our modules with the modules reported by GSE21687. Similarly, we constructed their co-expression network using WGCNA and identified 16 modules  by accession number  modules . The hypAs mentioned above, 31 out of 38 classified modules possessed miRNAs. We further calculated percentages of miRNAs in total genes in corresponding modules to detect miRNAs-enriched functional modules. Five modules with hypergeometric test FDR smaller than 0.05 were considered to be miRNA-enriched modules . More th9 , the log rank p-values of miR-24 were smaller than 0.05. Both miR-15a and miR-24 played important roles in various cancers. The findings we discovered may also be helpful in understanding the mechanisms of other cancers.We checked the association of miR-15a and miR-24 with survival in 21 TCGA cancers  using KM-plotter10 . In 13 cGenes (mRNAs) and microRNAs (miRNAs) were identified as molecular markers for clinical management based on the change of expression signatures in ependymoma . HoweverWe used high-performance computers to construct a co-expression network of 64 EPN samples with both mRNA and miRNA profiles. The network model passed strict and reasonable soft-threshold criteria to meet approximate scale-free topology. In our results, a total of 18,292 genes were clustered into 37 modules with intrinsic association (excluding 2933 genes in gray modules without association). We found that more than 80% of modules (31 out of 37) included miRNA, indicating an extensive participation of miRNA in the regulation of gene co-expression networks. Considering the complexity of tumor cell biological process, it is insufficient to investigate the pathogenesis of tumors from a single type of RNA alone, while analyzing co-expression profiles of integrated miRNA and mRNA pairs could identify the regulatory network for a prognosis of brain tumors .Subsequently, we performed functional enrichment analysis on clustered modules to determine gene groups that were intrinsically related to the progress of EPN. Interestingly, KEGG enrichment analysis showed that the most significant pathway was the cell cycle pathway in the red module, which was closely related to various intracellular molecular activities and cell proliferation capabilities. Development of the nervous system and brain evolution were affected by changes in the cell cycle of neural stem cells, which, with an out-of-control subpopulation growth, may transform into initial brain tumors in a cancer stem cell niche . The secConsistent with previous reports that the Synaptic vesicle cycle pathway is a key pathway for up-regulation in EPN , this stAs we all know, miRNA play a role in regulating mRNA expression through initiating transcriptional repression and introducing mRNA cleavage or degradation. We identified five miRNA-enriched modules (>10%), including oncogenic molecules miR-15a and miR-24-1, which were previously reported as poor prognosis biomarkers in child patients with ependymoma . Four taThree target genes  of miR-24-1 were detected in the co-expression network module (saddle-brown). After annotation, we found that they affected the development progress of tumors through three different signaling pathways. Firstly, MAP3K4 was involved in MAPK kinase signal transduction, which was a characteristic signaling pathway for discriminating group A subtype ependymoma . SecondlTo summarize, based on a weighted gene co-expression network approach, we identified enriched biological processes and pathways composed of associated genes that were related to ependymoma development. Our study reveals that, for the first time, the key regulatory mechanism of miRNAs is in promoting tumorigenesis and tumor development by analyzing co-expression network of miRNAs and mRNAs in ependymoma. Discoveries in the current study not only cover unexplored molecular mechanisms of miRNAs serving as a prognostic biomarker, but also propose novel genes that can be used for diagnosis signature and for potential antitumor treatment targets of ependymoma.https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21687.Publicly available datasets were analyzed in this study. This data can be found here: TH designed the experiment. FL and HD performed the experiment and analyzed the data. HD and ZM wrote the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The World Health Organization declared coronavirus disease 2019 a pandemic on 11th March 2020. There is concern regarding performing endonasal surgical procedures because of a high viral load in the nasopharynx. This paper describes our experience in conducting emergency and urgent endonasal operations during the peak of the coronavirus disease 2019 pandemic in the UK.To show the outcome of endonasal surgery during the peak of the coronavirus disease 2019 pandemic and to assess the post-operative rate of nosocomial coronavirus disease 2019 infection.A retrospective cohort study was conducted of all patients who underwent high priority endoscopic nasal surgery or anterior skull base surgery between 23rd March and 15th June 2020 at University Hospitals Birmingham NHS Trust.Twenty-four patients underwent endonasal surgery during the study period, 12 were males and 12 were females. There was no coronavirus-related morbidity in any patient.This observational study found that it is possible to safely undertake urgent endonasal surgery; the nosocomial risk of coronavirus disease 2019 can be mitigated with appropriate peri-operative precautions. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).4 This creates a major concern when managing patients requiring transnasal endoscopic surgery, especially with the use of micro-debriders and drills, which cause aerosolisation of SARS-CoV-2.5 Global reports mention a high rate of infection amongst otolaryngologists.6 There is a general fear across the world, and this is extended to and forms a particular challenge for endoscopic rhinology surgery in the management of cancers and life-threatening conditions.In addition to the transmission of infection to healthcare workers, there is concern about nosocomial Covid-19 infection. Research shows that there is a high viral load in the nasopharyngeal area.7 In such a situation, it is necessary to maintain a balance between deferring and performing transnasal endoscopic surgical procedures. There are very limited data showing the impact and outcomes of high priority surgery during this pandemic. This article presents the outcomes of transnasal endoscopic operations performed during the peak of the Covid-19 pandemic in a tertiary care hospital in Birmingham, UK.Trends show that there is likely to be a decline in the number of new Covid-19 cases; however, a further second or third peak has been predicted.9A retrospective study was conducted of 24 patients who underwent endonasal surgery, performed both by ENT surgeons and neurosurgeons, between 23rd March and 15th June 2020 at University Hospitals Birmingham NHS Trust, UK. This was the time frame when the UK declared a medical emergency and there was a peak in transmission rates.10 and underwent emergency or urgent endonasal surgery.11 One patient underwent surgery twice.After considering the priority levels for surgery as per the UK guidelines, a total of 24 patients were prioritised as level 1 or 2 ,10 and u11 Apart from one emergency epistaxis case, all patients self-isolated for 14 days before and 14 days after surgery. All operations were performed with full personal protective equipment (PPE), which included: a long-sleeved, fluid-repellent disposable gown and gloves; a filtering face piece (FFP) code 2 or code 3 mask; a FFP3 respirator and loose-fitting respirator hood; and a visor. Patients were monitored for any symptoms of Covid-19 infection before discharge and two weeks post-surgery.All patients were pre-operatively screened for Covid-19 infection with reverse transcription polymerase chain reaction testing, via the method described by national authorities.Informed consent was obtained from all patients, including the risk of acquiring Covid-19. All patients were managed according to the most up-to-date recommendations for surgery, following our hospital coronavirus priority operating plan. No separate ethical committee approval was sought as this was an observational study. Data were collected retrospectively, using medical records.Regarding statistical analysis, continuous variables are presented as means; categorical variables are expressed as frequencies and percentages.Twenty-four patients, 12 females and 12 males, underwent endonasal surgery during the study period, with 1 patient undergoing surgery twice. None of the patients had a history of recent travel. The patients’ age range was 19 to 84 years . The baseline patient characteristics are described in Thirteen of the patients had co-morbidities  and 4. FAll patients were discussed in a multidisciplinary meeting and were prioritised before surgery. They were all negative for Covid-19 at their pre-screening appointment. Six patients were priority level 1, with the remainder being priority level 2 .Table 5One patient had an overnight stay in intensive care for observation, with a lumbar drain inserted. The average hospital stay was 4 days. During endoscopic surgery, debriders and drills were avoided where possible. All operations were undertaken in full PPE. Post-operatively, no patient had any signs or symptoms suggestive of Covid-19 infection.12 None of the patients were symptomatic at discharge from hospital or at their first telephone follow up at two weeks.At the time of discharge, patients were instructed to self-isolate for a period of 14 days and asked to contact the UK Covid-19 helpline if they became symptomatic.14 Lei et al. identified a high rate of post-operative coronavirus infection.15 The most important aspect is the mortality associated with being operated on, and having Covid-19 or contracting it in immediate post-operative period.16 Although endoscopic nasal surgery is considered to be one of the most aerosol-generating procedures, our study showed a 0 per cent rate of infection with Covid-19.This article describes our experience of operating on nose and skull base lesions during the coronavirus pandemic on a high priority or urgent basis. The length of hospital stay was less than the median incubation period of SARS-CoV-2.17 however, the surgery was performed in a normal operating theatre, without additional precautions and PPE. In our study, the entire operating theatre team had taken appropriate measures, wearing full PPE.18Currently, there are sparse data on patients undergoing endoscopic nasal surgical procedures in the coronavirus era. Zhu and colleagues reported on a patient diagnosed with pituitary adenoma who unfortunately succumbed to Covid-19 and died of respiratory failure;We have demonstrated that urgent endonasal surgery may be undertaken, following careful patient selection and categorisation, in those prioritised as level 1 or 2, as long as there is a careful and thorough patient investigation.Primum non nocere (first do no harm); in acknowledgment of the significant progression of disease processes if left unchecked, we suggest that surgical teams, as described in this paper, consider the option of endonasal surgery for urgent cases, rather than alternative external, more invasive approaches or no treatment. All patients should be prioritised for these surgical procedures, and where appropriate discussed in a multidisciplinary team setting, taking into account the disease process and the harm caused by not operating or offering an alternative, non-endonasal option.20 Strict pre-operative and operative protocols should be followed for cases that cannot be deferred. Patients need to be thoroughly consented regarding the risks of surgery specific to the background rate of coronavirus in their locality and in relation to the anatomical region that is being operated on.•All patients should be prioritised for endonasal surgery•Prioritisation should consider the disease process and the harm caused by not operating or offering an alternative, non-endonasal option•Every hospital should establish their own local protocol based on the most up-to-date evidence, using national and international guidelines•Strict pre- and peri-operative protocols should be followedEvery hospital should establish their own local protocol based on the most up-to-date evidence, using national and international guidelines.In summary, our retrospective data of 24 patients who underwent 25 endonasal surgical procedures demonstrate a 0 per cent morbidity rate and mortality rate from operating endonasally in a controlled environment. We therefore recommend that patients with pathologies that demand urgent or immediate intervention not be denied the endonasal surgery route if this would have been the first-line approach before the Covid-19 pandemic.


Background: Video fluoroscopic swallowing study (VFSS) is considered as the gold standard diagnostic tool for evaluating dysphagia. However, it is time consuming and labor intensive for the clinician to manually search the recorded long video image frame by frame to identify the instantaneous swallowing abnormality in VFSS images. Therefore, this study aims to present a deep leaning-based approach using transfer learning with a convolutional neural network (CNN) that automatically annotates pharyngeal phase frames in untrimmed VFSS videos such that frames need not be searched manually. Methods: To determine whether the image frame in the VFSS video is in the pharyngeal phase, a single-frame baseline architecture based the deep CNN framework is used and a transfer learning technique with fine-tuning is applied. Results: Compared with all experimental CNN models, that fine-tuned with two blocks of the VGG-16 (VGG16-FT5) model achieved the highest performance in terms of recognizing the frame of pharyngeal phase, that is, the accuracy of 93.20 (±1.25)%, sensitivity of 84.57 (±5.19)%, specificity of 94.36 (±1.21)%, AUC of 0.8947 (±0.0269) and Kappa of 0.7093 (±0.0488). Conclusions: Using appropriate and fine-tuning techniques and explainable deep learning techniques such as grad CAM, this study shows that the proposed single-frame-baseline-architecture-based deep CNN framework can yield high performances in the full automation of VFSS video analysis. Dysphagia is defined as a clinical symptom of difficulty swallowing foods . NeuroloVideofluoroscopy swallowing study (VFSS) or a modified barium swallow study, is considered the gold standard tool for studying the oral and pharyngeal processes for evaluating the swallowing process of dysphasia patients . During The swallowing process is generally categorized into three phases—the oral, pharyngeal and esophageal phases, as shown in VFSS can illustrate the physiological process of the entire swallowing activity, including the motions of the jaws, tongue, palate, pharynx, larynx, esophagus and bolus of food . AlthougWith recent efforts to obtain objective and consistent evaluations of VFSS image data, as well as with the rapid development of artificial intelligence (AI) research on medical imaging, several deep learning-based VFSS analysis methods have been suggested. In particular, inspired by the recent success of temporal action detection technology on action classification and action recognition in videos, such as three-dimensional convolutional networks (3DConvNets) ,15, mediTherefore, to suggest a simple but practical computer-aided detection system using generic deep learning technology, this study proposes a single-frame-baseline-architecture-based  convolutTo recognize the pharyngeal phase in a long frame of raw VFSS videos, this study proposes a framework composed of three stages: training, classifying and temporal action grouping stages. In the first training stage, a CNN model is trained by a dataset, where each frame is labeled whether it is the pharyngeal phase. In the second classification stage, each frame in the test dataset video is classified using a predicted score (0.0–1.0) regardless of whether each image corresponds to the pharyngeal phase using the trained CNN model. In the third stage, we integrate the classification results on each frame using the sliding window technique to recognize the pharyngeal phase in untrimmed VFSS videos.The VFSS video data were taken from all 54 subjects who visited the Department of Rehabilitation Medicine at Korea University Anam Hospital from 1 March to 30 June, 2020, who were experiencing subjective swallowing difficulties. The subjects were 19 to 94 years old (mean age 70.67 ± 14.73 years) and included 29 men and 25 women.The collected VFSS dataset was recorded by rehabilitation medicine specialists who performed the VFSS based on the standard protocol . During The entire collected video clips were randomly segmented into training and testing sets at a ratio of 80:20. In order to avoid over-estimation, the division was performed on a subject basis. Consequently, among 54 subjects , 43 subjects  were used for training and 11 subjects  were used for testing.https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/, accessed on 14 September 2020). Because this study was designed as retrospective study, the requirement to obtain informed consent was waived. This study was approved by the Institutional Review Board of the Korea University Medical Center (IRB No. 2021AN0019) and carried out according to the guidelines of the committee.This study was conformity with the Declaration of Helsinki and Ethical Guidelines for Medical and Health Research Involving Human Subjects  is a class of deep neural network that is the most typically applied in analyzing visual images . CNNs caThis experiment was conducted using six different CNNs with different degrees of fine-tuning using VGG-16  as the bWhen the training dataset is relatively small, transferring a CNN pretrained by a large annotated dataset and fine-tuning it for a specific task can be an efficient method for achieving acceptable goals and lower training costs . AlthougThe 258 video clips selected as the training dataset were randomly segmented into five folds to perform five-fold cross validation to evaluate the model training while avoiding overfitting or bias [TM  with an Ubuntu 18 operating system, 256 GB of system memory and four NVIDIA Telsa V100 GPU. All the experiments were performed using the Keras [The training process above was repeated for all 12 experimental groups . All deehe Keras  library he Keras  backend Three specialists in rehabilitation medicine annotated and validated the pharyngeal phase occurrence. They annotated the start and end frames of all occurrences of the pharyngeal phase in all experimental VFSS video clips. According to medical criteria ,29, the To comprehensively evaluate the recognition performance of the pharyngeal phase on the test dataset, the accuracy, sensitivity, specificity, false positive rate (FPR), false negative rate (FNR), positive prediction value (PPV), Negative Prediction Value (NPV), diagnostic odds ratio (DOR), area under the receiver operating characteristic curve (AUC), Matthews correlation coefficient (MCC) and kappa were calculated as follows:TP and FP denote the number of correctly and incorrectly predicted frame images from the entire video clip in the test dataset, respectively. Similarly, TN and FN represent the number of correctly and incorrectly predicted frame images from the entire video clip in the test dataset, respectively.A sample of the evaluation process is shown in This study was conducted using experimental groups according to the degree of fine-tuning of one backbone deep CNN (VGG16). For each experimental group according to the number of trainable blocks (0 to 5) of the backbone deep CNN (VGG-16) used in this study, the number of non-trainable parameters, number of trainable parameters and training time of each experimental group are shown in Among all experimental groups, fine-tuned with all blocks of the VGG-16 model (VGG16-FT5) achieved the highest recognizing performance, that is, the accuracy of 93.20 (±1.25)%, sensitivity of 84.57 (±5.19)%, specificity of 94.36 (±1.21)%, FPR of 5.64 (±5.64)%, FNR of 15.43 (±5.19)%, PPV of 67.19 (±4.98)%, NPV of 97.84 (±0.72)%, DOR of 104.9054 (±36.92), AUC of 0.8947 (±0.0269), MCC of 0.716 1 (±0.0482) and Kappa of 0.7093 (±0.0488). All performance metrics values generated through 5-fold cross validation of each experimental group are presented in An automatic recognition of the pharyngeal phase frame from VFSS videos may be useful for the clinical analysis of VFSS. Clinically, the analysis of the pharyngeal phase in the VFSS video is important to the entire swallowing process, as it can identify any abnormalities that can result in serious medical complications, such as aspiration pneumonia or asphyxia . To asseThe CNN model learned from pre-training a large natural image dataset that can be used to classify common images but cannot be well utilized for specific classification tasks of medical images. However, based on a previous study that described the effects and mechanisms of fine-tuning on deep CNNs, when setting certain convolutional layers of a deep CNN model be trainable, the CNN model can be further specialized for specific classifying tasks ,31. EspeAs shown in Grad-CAM uses the gradient information flowing into the last convolutional layer of the deep CNN to understand the significance of each neuron for making decisions . For a qWhen the pharyngeal phase is recognized as a non-pharyngeal phase , the pharyngeal cavity was not imaged in the x-ray area as the patient moves and thus it was determined to be a similar part to the pharyngeal cavity A. Even iThis study has a limitation in that the sample size estimation method was not applied as it has only a limited set of data due to the characteristics of medical images that are limited to large-scale data collection. In addition, this study has a limitation in that it does not perform random sampling related to dataset sampling and uses sample of convenience that only uses VFSS videos taken at a certain time. The limitation of such a sampling method was mentioned in the previous literature , such asA single-frame-baseline-architecture-based simple CNN for recognizing pharyngeal phase in untrimmed VFSS video clips is presented here and the following conclusions are drawn. When using deep CNNs for recognizing the pharyngeal phase in VFSS video clips, by applying transfer learning technique to a deep CNN for classification, an appropriate fine-tuning degree was required. In addition, in the case of image classification using a deep CNN, classification must be evaluated qualitatively using visual interpretation methods such as the Grad-CAM technique to identify whether an appropriate classification has occurred based on the correct reason. The single-frame-baseline-architecture-based simple CNN using the factors above demonstrated the possibility of yielding high performances in the full automation of VFSS video analysis. However, this study was conducted based on images taken only in one institution and may have limitations compared to studies using multi-center and multiple imaging devices.


This article reports new measurements of laser-induced plasma hypersonic expansion measurements of diatomic molecular cyanide (CN). Focused, high-peak-power 1064 nm Q-switched radiation of the order of 1 TW/cm Molecular-recombination spectra are readily measured following optical breakdown in gases. The cyanide (CN) molecule can be recognized rather early for time delays of the order of 100 ns after cessation of the laser pulse [Pseudomonas aeruginosa [Cyanides are connected to many living organisms, and are created through artificial processes, but they are highly toxic. Human exposure can occur through accidental ingestion or inhalation of cyanides. Synthetic materials can be found in 21st century buildings and furnishings that produce toxic-combustion byproducts like hydrogen cyanide (HCN) when burned [ruginosa . Immune-ruginosa . DetectiDiatomic molecule CN has remained a target for improved detection capability and deeper understanding, largely because engineers cannot replicate its effectiveness for certain industrial applications with any other compound . For exaEngineering applications associated with plastic manufacturing that continue to use cyanide create a downstream problem for firefighters, analogous to that of fire victims mentioned above. Firefighters must go into buildings where plastics that may have used cyanide during their manufacture then evolve their constituents into the air as they are consumed by fire . Again, Engineers continue to look for means of obtaining CN properties that customers need but that do not have the potential health hazards that are present with CN ,8. EnginIn addition, CN is a component of vehicle exhaust ,13,14,15The standard experiment components were used for laser-induced breakdown spectroscopy, and were summarized previously, e.g., see , but werFor the generation of optical-breakdown microplasma, a singlet lens  was used close to the top entrance window of one arm of the chamber containing the 1:1 COIn previous experiments, captured shadowgraphs of the breakdown plasma  served tTwo typical images are reported here. First, E, gas density The expanding shockwave was clearly visible, including the central plasma kernel. The image was nearly spherical; previously reported shadowgraphs that utilized 850 mJ excitation would reveal stronger deviation from spherical symmetry than the images obtained with a 170 mJ/pulse. The expanding shockwave radius was consistent with previous assessments of hypersonic laser-plasma expansion images  that emppendency ,(1)R(τ)F and D denoting the focal length and the beam diameter at the lens, respectively, for 1064 nm IR wavelength, Subsidiary measurement utilized a pyroelectric laser-pulse energy meter  for determination of absorbed energy for the laser-induced plasma studies. Transmitted energy per pulse reakdown . For exareakdown ,24 with The experiment series for the measurement of CN molecular distribution after optical breakdown includes evacuating the cell to a nominal backing pump pressure of the order of 1 Pa  program that uses the Nelder–Mead algorithm  and was Unfiltered spectra contained an overlap of the C I 193.09 nm atomic carbon line in second order and the 2-2 CN band head of 386.19 nm, where filtered spectra only contained the 2-2 CN band head of 386.19 nm. C I 193.09 nm atomic carbon line in second-order Stark widths were evaluated for filtered and unfiltered spectra using peak-fitting programs. The difference between the filtered and unfiltered spectra was obtained by applying deconvolution. w was extrapolated [Electron number density bon line , measureapolated ,29 to amUsing the Taylor–Sedov blast-wave model (see Equation ), plasmaThe experiment series for the measurement of CN molecular distribution after optical breakdown for the flowing-gas mixture utilized a similar process as discussed in the previous sections. The experiments included supplying the cell with a constant flow of ultrahigh pure NApplying the NMT program to the filtered, line-of-sight molecular CN-spectra produced in the flowing-gas mixture yielded the results shown in Just as in the fixed gas mixture, unfiltered spectra contained an overlap of the C I 193.09 nm atomic carbon line in second order and the 2-2 CN band head of 386.19 nm, where filtered spectra only contained the 2-2 CN band head of 386.19 nm. The C I 193.09 nm atomic carbon line in second-order Stark widths was evaluated for filtered and unfiltered spectra using peak-fitting programs, and the difference between filtered and unfiltered spectra was obtained by applying deconvolution. Using Equation , electroIn view of the shadowgraphs that were recorded in the 0.5 to 1 ange see , it woul spectra ,31.z-direction corresponds to slit height, and line-of-sight integration was along the y-direction in view of z were inverted for each wavelength The use of Chebyshev polynomials for Abel inversion of integral equationThe radial spectra were computed from the two-dimensional line-of-sight data see  that werAnalysis of Abel-inverted data was expected to reveal similar results for the shockwave, but in view of the shadowgraphs in The main results of the work are summarized here: Primarily shockwave expansion affects the formation of CN molecules as the plasma expands. For time delays of the order of 1 Laser-plasma expansion following optical breakdown occurs at well above hypersonic speed. Measurements of recombination CN spectra within the first few microseconds yielded results as expected from atomic hydrogen Balmer series laser spectroscopy: Analysis revealed higher electron and higher CN excitation temperature near the shockwave than in the central region for time delays of the order of one microsecond. The expansion characteristics were deduced from systematic analysis of the recorded line-of-sight spectra. Application of Abel inversion was reasonable and supported by shadowgraphs recorded in SATP air for laser-plasma initiation for similar energy/pulse, as utilized for measurements of molecular spectra.Further development of CN diagnosis with laser spectroscopy should focus on accurate measurements of spatial distributions with simultaneous recording of spectra at different angles. This would allow the examination of deviation from spherical symmetry by invoking inverse Radon transforms, viz. by applying computed tomography. For the various applications mentioned in this work, measurements of spatial distribution as plasma expands would also alleviate averaging along the line of sight.


Severe Acute Respiratory Syndrome Coronavirus 2 pandemic has infected millions of people. The conjunctival epithelium is easily exposed to infectious droplets and body fluids making eyes a potential route and reservoir of the infection. The CD147 and ACE2 receptor has been demonstrated in ocular surface cells, which implies that these cells may facilitate as a portal of entry for transmission of Severe Acute Respiratory Syndrome Coronavirus 2. Despite low viral load in tears and conjunctival swab, the negative RT-PCR results cannot exclude the possibility of the presence of Severe Acute Respiratory Syndrome Coronavirus 2 in ocular secretions. Pathogens might be transported by constant tear flow through the lacrimal duct system to the respiratory tract causing infection. Eyes are unlikely to be the main transmission route, however, their role in the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 cannot be overlooked. Therefore, proper eye protection should be instituted while attending Severe Acute Respiratory Syndrome Coronavirus 2 positive individuals, especially by health professionals. The main route of transmission of SARS-CoV-2 seems to be airborne droplets, close contact with an infected person, or contact with infected fomites. The ocular transmission has also been reported with great concern1 Especially, hand-eye contacts may play an intrinsic role in transmitting the virus. The eyes may represent a source of transmission through infected tears as well as a window for infection via respiratory droplets and aerosolized particles coming in contact with the conjunctiva.2Respiratory viruses cause numerous diseases in humans, including several ocular tropisms. The main reason for this is the easy contamination of conjunctival epithelium by infectious droplets and bodily fluids.3 among patients with SARS-CoV-2 infection showed aggravated ocular symptoms in 27%, among which 11% had prodromal ocular symptoms.A study by Nan Hong et. Al.Ocular symptomatology is relatively common and may present just before the onset of respiratory symptoms. The ocular manifestations such as follicular conjunctivitis have been repeatedly noted as an initial or subsequent symptom of SARS-CoV-2-positive patients.4, the prevalence of ocular signs and symptoms varies from 0 to 31.58% while the detection rate of SARS-CoV-2 in the ocular sample ranged from 0 to 11.1%. Conjunctivitis was a relatively rare occurrence. The ocular manifestations were not always consistent with the detection of SARS-CoV-2 infection by reverse transcription-polymerase chain reaction (RT-PCR), done in the conjunctival swab samples and the opposite was also found to be true.In a systematic review5, thereby potentially colonizing the respiratory tract. This implies the eyes to be the potential site of infection and gateway for the respiratory infection.The nasolacrimal system acts as an anatomical bridge between two systems: the respiratory and the ocular system. The natural mechanism of tear flow dynamics from the ocular surface to the inferior meatus via the nasolacrimal system might also facilitate the movement of virus particles from the ocular surface to the respiratory tract6 Previous studies point out CD147 as a transmembrane glycoprotein, a new spike protein (SP) receptor, and the interaction between CD147 and SP facilitates SARS-CoV-2 invasion of host cells.7 The presence of ACE2, another receptor revealed that ocular surfaces are susceptible to SARS-CoV-2 infections, and these cells may result in the transmi ssion of this virus to a human.1 Both CD147 and ACE2 have been demonstrated in ocular surfaces cells, these cells may serve as a portal for entry and reservoirs for the person to person transmission of respiratory virus like SARS-CoV-2.The structure of the cellular receptors and their distribution in respiratory and ocular systems are likely to aid the tissue tropism of most of the respiratory viruses, that now includes SARS-CoV-2, such as the host epithelial cell glycoproteins bearing terminal sialic acids which are thoroughly distributed all over the respiratory and ocular system. It indicates that ocular discharges containing viruses may come in contact with the respiratory tract through the nasolacrimal route and lead to infection manifesting as pneumonia.8 Significantly low detection of human-CoV-RNA by RT-PCR in conjunctival secretions from patients with SARS-CoV-2 may be related to the relatively low sensitivity of the current RT-PCR technique, later timing of sample collection, along with activation of the host immune system, significant increases in lactoferrin, secretory IgA levels in tears and increase in circulating IgM and IgG levels in plasma. Similar was demonstrated with SARS. Hence, negative RT-PCR results cannot exclude the possibilities of the presence of SARS-CoV-2 in ocular secretions.9The virus concentration in tears seems to be significantly less in comparison to the respiratory samples. Even PCR done on pharyngeal swab has an approximately 30% positive rate, thus making it more difficult to detect SARS-CoV-2 on the ocular samples. Also, the amount of sample that can be collected from the eye surface is naturally limited9 Studies suggest the eye is less often involved in SARS-CoV, Middle East Respiratory Syndrome-CoV (MERS-CoV), and 2019-nCoV infection. Even conjunctivitis has been less reported in SARS-CoV-2 and never reported in SARS and MERS patients.9 This hints that the eye is neither a preferred organ nor is a suitable entry point for human CoV infection that enables the virus to colonize and infect the respiratory tract. However, the pathogens that come in contact with the ocular surface might be transported by regular drainage of a tear through the lacrimal duct system to reach the respiratory tract and cause infection.9 Some studies also have shown ocular symptoms to be relatively common in SARS-CoV-2.3 Whilst the eye is unlikely to be the main transmission route, its role in the transmission of SARS-CoV-2 cannot be excluded.4Considering the vulnerability of the conjunctiva to the infectious droplets and fomite transmission, anatomical and physiological connection between mucosa of the upper respiratory tract and ocular surface and presence of same entry receptor in both respiratory and ocular surface for some respiratory viruses including SARS-CoV-2, the role of eyes in human coronavirus infection is crucial and cannot be overlooked.1 One of the risk factors for the nosocomial infection of medical personals with SARS was whether they wore protective goggles. Only one percent of the clinicians wearing eye protection were infected compared to eight percent of the clinicians infected who did not wear eye protection.10 Similar is true in SARS-CoV-2 infection3 thus optimal use of eye safety measures is mandatory.Considering the high viral aerosol load in the hospital, the ocular transmission route should be seriously considered. A breach in eye protection may lead to exposure of the ocular surface to potentially infectious agents like virus, which may then transmit to the hands through eye-hand contact and eventually to other mucous membranes like the mouth. Therefore, along with regular masks, gowns, and gloves; goggles, and frequent hand washing, especially for medical personals who are in close proximity with SARS-CoV-2 patients is utmost.2Ocular symptoms are found to be relatively common and viruses have also been demonstrated particularly in those with ocular symptoms with SARS-CoV-2. Therefore, there is a possibility of the virus transmitting from the ocular surface. All health workers should be vigilant about ocular symptoms consistent with SARS-CoV-2 infection, and optimally use eye protection such as goggles or face shields as an absolute part of the standard personal protective equipment, and should consider tears, ocular discharges, and ocular contaminants to be potentially infectious.Based on the anatomical, molecular, and current clinical evidence, the possibility of the ocular surface being an infection gateway is low but the role of the eyes in the transmission of SARS-CoV-2 infection cannot be overlooked and ought not to be underestimated. SARS-CoV-2 infection or transmission through the ocular surface may be a potential infection route, especially in hospitals where infected aerosols are frequent. Therefore, appropriate ocular protection is very important to prevent infection, especially for medical personnel.


The novel coronavirus (COVID-19) pandemic has led to an increase in the number of patients presenting to the emergency department (ED) with severe hypoxia and acute respiratory distress. With limited resources and ventilators available, emergency physicians working at a hospital within the epicenter of the United States outbreak developed a stepwise, non-invasive oxygenation strategy for treating COVID-19 patients presenting with severe hypoxia and acute respiratory distress.2 (blood oxygenation saturation) 55% on room air. Emergency physicians employed a novel non-invasive oxygenation strategy using a nasal cannula, non-rebreather, and self-proning. This approach led to a reversal of the patient’s respiratroy distress and hypoxia (SpO2 88–95%) for the following 24 hours. This non-invasive intervention allowed providers time to obtain and initiate high-flow nasal cannula and discuss end-of-life wishes with the patient and his family.A 72-year-old male suspected of having the COVID-19 virus presented to the ED with shortness of breath. He was found to be severely tachypneic, febrile, with rales in all lung fields. His initial oxygen saturation registered at SpOOur case highlights a stepwise, organized approach to providing non-invasive oxygenation for COVID-19 patients presenting with severe hypoxia and acute respiratory distress. This approach primarily employs resources and equipment that are readily available to healthcare providers around the world. The intent of this strategy is to provide conventional alternatives to aid in the initial airway management of confirmed or suspected COVID-19 patients. The novel coronavirus disease COVID-19) pandemic, caused by the highly contagious severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is currently threatening the global human population.9 pandemiThe COVID-19 pandemic has led to an increase in the number of patients presenting to the hospital with severe hypoxia and acute respiratory distress. We employed a novel non-invasive oxygensation strategy using a nasal cannula (NC), non-rebreather (NRB), and self-proning. This technique led to an improvement in the patient’s hypoxia and a 24-hour reversal in his acute respiratory failure, which allowed us time to obtain and initiate high-flow NC and discuss end-of-life wishes with the patient and his family.Our case highlights a stepwise, organized approach to providing non-invasive oxygenation for hypoxic patients in acute respiratory distress. It was developed during the initial days of the COVID-19 pandemic at a frontline hospital at the epicenter of the US outbreak. This approach employs resources and equipment readily available to healthcare providers around the world. The intent of this strategy is to provide conventional alternatives to aid in the initial management of confirmed or suspected COVID-19 patients with acute hypoxic respiratory failure.A 72-year-old male presented to the ED for shortness of breath that had progressed over the prior seven days. He was found to be tachypneic, febrile, and with rales in all lung fields. His blood pressure and heart rate were within acceptable limits. He was awake, alert and cooperative. However, his oxygen saturation upon presentation to the ED was abnormal and initially registered at 55% on room air. The patient was placed on a cardiac monitor with pulse oximetry, and we obtained a chest radiograph revealing multilobar pneumonia .We employed a non-invasive oxygenation strategy using a NC at 6 liters per minute (LPM) and a NRB mask at 15 LPM. In addition, the patient was assisted to the prone position on the stretcher. Within five minutes, his mental status and work of breathing improved, his oxygen saturation improved to 95%, and he remained between 88–95% for the next 16 hours. Approximately 16 hours after arrival, the patient became hypoxic with oxygen saturations dipping below 88%. The NC was removed and a high-flow nasal cannula (HFNC) 60 LPM was added. Using this strategy of a HFNC, NRB, and self-proning, the patient remained alert and his oxygen saturation remained between 88–95% for a total of 24 hours.What do we already know about this clinical entity?A common presentation of symptomatic patients with coronavirus disease 2019 (COVID-19) is severe hypoxia and respiratory distress often requiring emergent intubation in the emergency department (ED) setting.What makes this presentation of disease reportable?We present a COVID-19 patient presenting to the ED with profound hypoxia and respiratory distress and rather than intubate, we employed a novel stepwise approach to non-invasive oxygenation.What is the major learning point?A stepwise approach to non-invasive oxygenation of COVID -19 patients can delay emergent intubation, allow time for additional ventilatory treatments to become available, and provide time for emergency providers to clarify goals of care with patients and their family.How might this improve emergency medicine practice?Resuscitating the hypoxic COVID-19 patient is uniquely challenging and necessitates a stepwise approach for both provider safety and patient care.Eventually, his mental status waned, his work of breathing became labored, and his oxygen saturation further deteriorated. Discussions with the patient and his family regarding advance directives revealed that his wishes were to be full code. He was admitted to the intensive care unit (ICU) and soon placed on a ventilator. Ultimately, our non-invasive strategy did not reverse this patient’s respiratory failure. However, it did allow us time (24 hours) to stabilize him, procure additional resuscitative resources, and discuss advance directives with him and his family.We present a stepwise approach to providing non-invasive oxygenation to confirmed or suspected COVID-19 patients presenting to the ED with hypoxia and acute respiratory distress. This strategy was developed during the initial days of the COVID-19 pandemic at a frontline hospital at the epicenter of the US outbreak. As in the case of our patient, this approach can be used to improve oxygen saturation, work of breathing, and may reduce the need for early mechanical ventilation.Our pathway does not include non-invasive positive pressure ventilation (NIPPV). We did not have masks or helmets available that would have sufficiently protected staff from aerosolization of the COVID-19 virus during NIPPV. In addition, due to limited resources, we needed to repurpose all of our bi-level positive airway pressure machines into ventilators.Patients presenting to the ED during the COVID-19 pandemic with symptoms such as fever, dyspnea, and hypoxia should be suspected of having the COVID-19 virus.3Contact and droplet precautions should be initiated for all patients suspected of having COVID-19, and providers should wear personal protective equipment (PPE) that includes a gown, gloves, eye protection, and a respirator .Patients presenting to the ED with confirmed or suspected COVID-19 should receive an initial assessment that includes evaluation of their airway, breathing, and circulation. The patient should be placed on a cardiac monitor to evaluate blood pressure, heart rate, and breaths per minute. Continuous pulse oximetry should be obtained. However, the presence of hypoxemia alone should not trigger intubation, as hypoxemia is often remarkably well tolerated in patients with COVID-19.5Patients with COVID-19 differ in some ways from other patients with acute respiratory failure. On presentation to the ED, most have significant hypoxia without other organ failures and without hypercapnia. The interventions described here as well as the inclusion/exclusion criteria  are buil6Supplemental oxygen is the mainstay of treatment of hypoxic patients, and for the majority of patients should begin with non-invasive maneuvers. If initial resuscitation strategies fail, if the patient becomes altered or shows continuing signs of respiratory failure, then he or she should be placed on mechanical ventilation. The remainder of this report describes our stepwise, non-invasive oxygen strategy for hypoxic patients with suspected or confirmed COVID-19.2) of 44%.9Initiate non-invasive oxygenation using a NC at 6 LPM. At room air, the air we breathe consists of 21% oxygen. A NC at 6 LPM equates to fraction of inspired oxygen  80% at triage demonstrated an improved SpO2 (94%) after five minutes of self-proning.14Patients should rotate every 30–120 minutes from prone position to left-lateral decubitus, right-lateral decubitus, and upright sitting positions. A recent observational cohort study revealed that patients presenting to the ED during the COVID-19 pandemic with moderate to severe hypoxemia, periperal oxygen saturation (SpO2 of nearly 100% and add about three to five cm H2O of positive-end expiratory pressure.2 via oral inhalation. We also recommend self-proning of patients to improve O2 delivery and reduce respiratory effort.The next step in our non-invasive oxygenation strategy includes employing a HFNC in conjunction with a NRB and self-proning. HFNC warms oxygen to 37° Celsius creating 100% humidity, and when set to high flow rates 60 LPM can achieve FIOThe novel coronavirus COVID-19 triggered a global pandemic leading to the infection of millions of individuals worldwide. Critically ill patients infected with COVID-19 often present to the ED with hypoxia and acute respiratory distress. The sheer scope and size of this pandemic has led to limited ventilator supplies and resources. Speaking with family members and determining wishes in patients who may not be good candidates for invasive ventilation is more time-consuming than ever before as most hospitals are limiting or banning visitors, and any procedure that can delay or prevent intubation has significant value.With limited data and supplies during the COVID 19 pandemic, novel strategies have been stressed as a bridge therapy for the patients with hypoxemia and respiratory distress. Our case report describes a stepwise approach to providing non-invasive oxygenation for confirmed or suspected COVID-19 patients presenting to the ED with hypoxia and acute respiratory distress.This strategy was developed during the initial days of the COVID-19 pandemic at a frontline hospital at the epicenter of the US outbreak. As in the case of our patient, this approach can be used to improve oxygen saturation, work of breathing, and reduce the need for early mechanical ventilation. Further evidence is needed to support causality and determine the effect this non-invasive has on disease severity and mortality.


The observations of some recent epidemiological studies offer hope for a reduced impact of COVID-19 for countries which practice universal BCG vaccination policy.This report provides a correlation between the case fatality rates of COVID-19 and the percentage of BCG vaccination coverage in 183 most affected countries. The main objective of this observational ecologic report is to evaluate possible effects of the previous BCG vaccination in different populations and the epidemic outcomes specially the rates of severe/critical cases and case fatalities. The analysis is preliminary since it is based on constantly rolling data while the COVID-19 pandemic is still unfolding.Our findings seem to support the fact that an older BCG vaccine may have a protective role in avoiding severe/critical SARS-CoV2 pneumonia and relatively decrease its fatalities. Several reports showed that exaggerated immune response of COVID-19 contributes to severe disease [As the BCG vaccine is already approved for human use, it is known to boost the immune system and modulate the exaggerated immunity response against tuberculosis . It provIt is hypothesized that, until a specific vaccine is developed, SARS-CoV-2 vulnerable populations could be immunized with BCG vaccines. Such a strategy would also be suitable for frontline health personnel .The aim of this perspective is to correlate between the COVID-19 case fatality rates, serious/critical case percentage, and percentage of national BCG vaccine coverage.methodology, to evaluate the effect of BCG vaccine, we included the BCG coverage percentage in 183 countries , countries which had included the vaccine in the past but do not do so currently, and countries who currently have BCG vaccine included in their NIP) and the COVID-19 infection rate, mortality levels, prevalence of serious/critical cases, and case fatality rates  as well as negative correlation between BCG coverage and incidence rate of all cases as well as serious and critical cases of COVID-19 among the studied countries (P = 0.001).As for data published from the WHO first announcement of the disease to 18th May 2020, when we analyzed the available data on BCG coverage , WHO COVID-19 status reports [Since the beginning of the pandemic, it was noticed that countries with BCG vaccination program appear to have a lower incidence and death rate from COVID-19 as compared to countries without such a program , 10. TheHowever, many reports do not support the BCG hypothesis that all existing claims are based on cross-country correlations , 16. WheBCG vaccine correlates with COVID-19 case fatality rates and probably offers protection against severe/critical cases of SARS-CoV-2. Recommended work through randomized controlled trials to determine how fast a BCG-induced protective immune response against COVID-19 develops is needed to validate its use as immune prophylaxis for more exposed population as healthcare workers.http://www.bcgatlas.org/) [The findings of the current report should be viewed within the limitation that these data are rapidly changeable; the majority of the studies use publicly available data repositories such as Worldometer to source COVID-19-related data . In the as.org/)  and othe


Internet-based self-help interventions for individuals with depressive symptoms, in which the main component is often a web-based self-help program, have been shown to be efficacious in many controlled trials. However, there are also trials on self-help programs showing no significant effect when delivered in routine care, and some studies report high dropout and low adherence rates. Research suggests that these findings do not emerge primarily due to the specific content of a self-help program. It seems more important how a program is embedded in the context of human and automated support before and during the use of a self-help program.This study aims to better understand the effects of 4 supportive contextual factors on outcomes of and adherence to a web-based self-help program for depressive symptoms. In a factorial experiment, 2 of 4 supportive factors, for which there is evidence for their role on outcomes and adherence, are realized during the intervention—personal guidance and automated email reminders. The other 2 factors are realized before the intervention—a diagnostic interview and a preintervention module aimed at increasing the motivation to use the program with motivational interviewing techniques.The study is a full factorial randomized trial. Adults with mild to moderate depressive symptoms  are recruited from the community through the internet and conventional media. All participants receive access to a web-based self-help program based on problem-solving therapy. They are randomized across 4 experimental factors, each reflecting the presence versus absence of a supportive factor  resulting in a 16-condition balanced factorial design. The primary outcome is depressive symptoms at 10 weeks post assessment. Secondary outcomes include adherence to the program, anxiety, stress, health-related quality of life, possible negative effects, and treatment satisfaction. Potential moderators and mediators  will also be investigated.Ethical approval was received on January 20, 2020. The study was initiated in February 2020, and 240 participants have been enrolled in the study as of November 1, 2020. Recruitment for a total of 255 participants is ongoing. Data collection is expected to be completed by May 2021.A better understanding of relevant supportive factors in the dissemination of web-based interventions is necessary to improve outcomes of and adherence to web-based self-help programs. This study may inform health care systems and guide decisions to optimize the implementation context of web-based self-help programs for depressive symptoms.ClinicalTrials.gov NCT04318236; https://clinicaltrials.gov/ct2/show/NCT04318236DERR1-10.2196/21207 Depression is one of the most common mental disorders that burdens society and individuals psychologically and financially ,2. PsychInternet-based self-help interventions complement existing interventions in health care, addressing some of their limitations. Potential advantages of internet-based self-help interventions include that they are easily accessible, provide a high degree of anonymity, can be used independently of time and place, and can be provided to many people simultaneously. Hence, many authors suggest internet-based self-help interventions as a possibility to complement face-to-face psychotherapy to improve mental health care .g=0.02-1.56). One study [Although internet-based self-help interventions effectively reduce depressive symptoms, their potential might not be fully exploited. For example, studies  about inne study  that invne study ,16.One reason for diverging outcomes and adherence seems to be the degree of human support and guidance provided before and during the use of a self-help program. Current literature suggests that unguided internet interventions without human support at any stage tend to be associated with high dropout rates , lower aIn the review , the autOther aspects that potentially improve internet-based self-help intervention outcomes and adherence can be automated and realized without human contact. There is limited evidence that automated email reminders may improve adherence and outcomes of internet interventions. For example, a study  that comAnother possibility for increasing outcomes of and adherence to internet-based self-help interventions is to enhance the motivation of participants. A well-known method in face-to-face treatments to address ambivalence and enhance motivation is motivational interviewing . High efThus, several supportive contextual factors have been associated with better outcomes and increased adherence. Yet, it is not entirely clear which factors are crucial for a significant enhancement of internet-based self-help interventions. Consequently, clear guidelines for how to optimally embed internet-based self-help interventions into a context of supportive factors are missing. To fully exploit the potential of internet-based self-help interventions, dismantling studies are needed to understand how and which supportive factors are essential when disseminating internet-based self-help interventions. Often, studies that investigated the influence of a specific supportive factor such as guidance had other factors in their study design that potentially confounded the effect of guidance . Therefore, only conclusions about the whole treatment package  and not about individual supportive factors  were possible. This entanglement limits insight into both the main effect of a given factor and possible interactions with other factors.One reason for limited insight into essential supportive factors may be reliance upon RCTs in internet-based self-help intervention research. Although RCTs are the gold standard for establishing the efficacy or effectiveness of an intervention, they are not suited for investigating the effects of single supportive factors or specific treatment components. Because RCTs only compare the whole multifactorial intervention (treatment package) with another intervention or a control group, specific mechanisms are confounded with one another. Therefore, it is only possible to draw conclusions about the whole treatment package and not about the main and interactive effects of specific factors .A new approach to getting more insight into how treatments work is the multiphase optimization strategy, which integrates perspectives, approaches, and concepts of various sciences . CollinsThe multiphase optimization strategy presents several experimental designs to optimize interventions. The most frequently used in behavioral sciences is the factorial design -36. ThisThis study aims to further clarify the optimal context of support of internet-based self-help interventions for depressive symptoms. It uses a factorial design to test the impact of 4 factors and their combinations. These factors are (1) a diagnostic interview conducted before the intervention, (2) a preintervention module using techniques of motivational interviewing accessible before the intervention, (3) human guidance during the intervention, and (4) automated email reminders during the intervention.The study, including assessments and the self-help intervention, will be conducted online. Participants will not receive any financial reimbursement for taking part in the study. The study consists of a full factorial trial that includes 4 experimental factors. Each factor will be evaluated at 2 levels (either present or absent), resulting in a 16-condition (2×2×2×2) balanced full factorial design . FactoriEligible participants are German-speaking residents of Switzerland, Germany, Austria, and Lichtenstein. Inclusion criteria are (1) being at least 18 years of age; (2) meeting criteria for mild to moderate depression  ; (3) proInterested participants can leave an email address on our study website . ParticiIf individuals are excluded, they can make use of the intervention outside of the study. However, participants reporting suicidal ideation first need to confirm that they are in touch with their emergency contact or a psychotherapist. We offer to provide a contact for professional psychological help in case participants are severely depressed.Participants are recruited through depression-related websites, radio interviews, self-help groups, Facebook groups, Google ads, and the website of the University of Bern (Switzerland). The description of our study includes a link to the study website. Written informed consent to participate in the study is obtained from all participants.Herausforderungen meistern  (HERMES) is based on problem-solving therapy [The web-based self-help program  therapy . The fir therapy . Results therapy .Within the factorial design, 4 factors are realized. The first factor consists of a diagnostic telephone interview conducted before the self-help program. The second factor is a preintervention module based on motivational interviewing presented before the self-help program. The module aims at initiating a reflection process about one’s motivation for using the intervention . The thiAll outcome measures will be assessed online with validated German versions of the original questionnaires.Symptoms of depression will be assessed with the self-reported measure Patient Health Questionnaire–9 . The Patz scores of these indicators. Furthermore, and for exploratory purposes, we will also run the analyses with each of these indicators of adherence. Symptoms of anxiety will be assessed with the Generalized Anxiety Disorder–7 [Adherence is defined as the extent to which participants use the intervention. Following the suggestion of Donkin et al , a composorder–7 . Symptomsorder–7 . Health-sorder–7 ,47. Suicsorder–7 ,39. Probsorder–7 ,49.Possible adverse effects of the intervention will be assessed with the Inventory for the Assessment of Negative Effects of Psychotherapy . Client Demographic information about participants will be assessed at baseline. Treatment expectancy will be assessed with the Credibility/Expectancy Questionnaire . WorkingThe online platform Qualtrics  randomizes participants in 2 steps. First, after T0 and before any contact with the study team, participants are randomized automatically to 1 of 4 groups . The first randomization is stratified (either mild or moderate depressive symptoms). Second, after 2 weeks and completing T1, participants are randomized to 1 of 4 groups . Both times, block randomization ensures a balance in sample size across groups over time. A schedule of enrollment and participation is shown in Participants complete questionnaires at all 5 time points online via Qualtrics. We manually invite participants to complete the baseline questionnaire (T0). The 4 subsequent time points  are automatically triggered once T0 is completed. We try to limit the amount of missing data from survey attrition by reminding participants after 5 and 10 days to complete the questionnaires.Statistical reporting will follow CONSORT  and CONSTo test for the main and interaction effects of treatment components on primary and secondary outcomes, linear mixed model analysis of variance will be used. This approach uses all available data on each subject and does not involve the substitution of missing values but estimates parameters about missing values. However, sensitivity analyses will explore the impact of the imputation of missing values before computing the mixed models. The main effects and interactions will be based on aggregates across experimental conditions. The purpose of the factorial experiment is not to compare the 16 conditions to each other but to estimate the main effects of the 4 factors and interactions between the factors. For example, the main effect of the diagnostic interview will be estimated by comparing the mean of the experimental conditions in which this factor is present (conditions 1-8 in d=.35) for main effects and interactions between 2 factors  on change in depressive symptoms (G-Power 3.1). From a clinical perspective, smaller effects are considered to be less relevant [r=.60. For a factorial design, this signifies a sample of n=204 to detect effects. Because we expect a dropout rate of about 20%, the planned sample size is n=255. For every condition, roughly 15 participants are required.We conducted an a priori power analysis for small-to-medium effect sizes  approved the study on January 20, 2020 (2019-01795). Recruitment started in February 2020. As of November 1, 2020, out of 1480 interested individuals, 409 individuals have completed T0, and 240 participants have been enrolled in the study.The study was registered at ClinicalTrials.gov (NCT04318236). The ethics committee of the canton of Bern  and mediating  effects will be tested. Furthermore, negative effects of psychotherapy, treatment satisfaction, system usability, and dropout rates will also be measured and inspected. This study builds on a wealth of encouraging efficacy studies of internet-based self-help. It promises to provide a more detailed insight into which supportive context factors enhance outcomes of and adherence to internet-based self-help interventions for depressive symptoms. Furthermore, the study may also inform about possible mediation and moderation effects that could provide more information about how or why internet-based self-help interventions for depressive symptoms work.Our study has been designed to shed more light on the supportive context of internet-based self-help interventions. It deconstructs a treatment package and explores active and inactive supportive factors. Understanding which factors do and do not work will help us get closer to the goal of delivering internet-based self-help interventions optimally. According to the guidelines of multiphase optimization strategy, a future RCT should test an intervention providing an optimal supportive context based on our findings, against an intervention providing a context that is usual in studies about internet-based self-help interventions . With such a study, the possible superiority of the optimized context could be established.Limitations of this study are comparable to those of the majority of studies about internet-based self-help interventions. The sample of this study is self-selected and participants become aware of our study through the internet. This limits the generalizability of possible findings to regular clinical settings or individuals that rarely use the internet.To improve outcomes to future internet-based self-help interventions for depression, this study could provide recommendations on how to optimize the context of human and automated support. Based on findings of active and inactive factors and the interactions thereof, recommendations could be made for future research and the implementation and dissemination of internet-based self-help interventions in routine care.


To investigate the course of anxiety and depression before and after transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and in the postoperative 1st month when the histopathological biopsy result was obtained. In between June 2017- January 2019, 204 patients who underwent TRUS-Bx and completed the questionnaires assessing anxiety and depression were included in the study. Questionnaires were completed immediately before the biopsy, immediately after the biopsy and at the end of the first month when the histopathological biopsy results were given. State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS) and perceived stress scale (PSS) forms were used to assess anxiety and depression. After the histopathological examination patients were divided into two groups as patients without cancer (Group 1) and with cancer (Group 2). Data was compared between the groups. PSA level was negatively correlated with STAI TX-1 scores of the patients immediately after TRUS-Bx, whereas it was positively correlated with STAI TX-1 and TX-2 30 days after the TRUS-Bx. PSA level was positively correlated with HADS-A and HADS-D scores immediately before and 30 days after TRUS-Bx. Biopsy results showed a significant difference in 30 day post-biopsy related data. STAI TX-1, STAI TX-2, HADS-A, HADS-D and PSS scores were higher in Group 2 compared with Group 1. Pre-biopsy anxiety disappeared after bx, but there was a significant increase in anxiety and depression in patients after the diagnosis of malignancy. Patients were seriously concerned about the diagnosis of prostate cancer. Through the widespread use of prostate-specific antigen (PSA), earlier detection of prostate cancer (PCa) at lower stages, lower grades, and smaller tumor volumes is feasible. Contemporary PCa screening modalities such as PSA and digital rectal examination (DRE) are two parameters used to predict the detection of PCa   . TransrProstate biopsy can cause psychological and physical impacts   . CancerWade et al. investigated the psychological impact of TRUS-Bx, including relationships between physical biopsy-related symptoms and anxiety/depression using the Hospital Anxiety and Depression Scale (HADS) in a prospective observational study of 1144 men undergoing standard TRUS-Bx   . In anoIn this prospective study, we aimed to investigate the course of anxiety and depression before and after TRUS-Bx and to evaluate the factors that affect patient anxiety and depression.After receiving ethical approval from the ethics committee of our institution  and the written informed consent form from all participants, patients with the ability to read and answer the questionnaire forms who underwent prostate biopsy due to elevated PSA or abnormal digital rectal examination from June 2017 to January 2019 were prospectively evaluated. Patients were excluded if they were under 40 years old, had prior prostate biopsy, had a diagnosed psychiatric disease such as psychosis, depression, mental retardation, and dementia, prior or concomitant malignancies, history of serious cardiovascular disease and end stage renal disease.Patient’s age, PSA level, education level, rectal examination result, prostate volume, pain scores  just after the biopsy procedure) and TRUS-Bx pathological results were recorded. Patients underwent standardized 12-core TRUS-Bx with periprostatic blockage. Patients received antibiotic therapy for 5 days from the day of biopsy.All patients who participated in the study completed the self-report questionnaires assessing anxiety and depression immediately before biopsy, immediately after biopsy and 30 days after biopsy when the histopathological biopsy results were given. In all groups, correlation between patient’s demographics and questionnaire results was investigated. After the histopathological biopsy results were given, patients were divided into two groups as benign pathology of the prostate (Group 1) and PCa (Group 2). Then, patient’s demographics and questionnaire results were compared between the groups. In addition, ∆ scores for the questionnaires, which is the difference between immediately before biopsy and 30 days after biopsy, were compared between the groups. Patients with clinically insignificant PCa (defined as grade group (GG) 1 PCa detected in ≤2 cores and <50% of any one core) and clinically significant PCa (others) were recorded. Correlation between patient’s demographics and questionnaire results was also investigated in group 2.Appendix) and perceived stress scale (PSS) forms. The STAI form includes two scales: State anxiety scale (TX-1)  and Trait anxiety scale (TX-2)  ( Anxiety and depression were measured using the State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS) (points)   . The scpoints)   . The peData were analyzed using the Statistical Package for Social Sciences, version 20.0  software program. The sample size was calculated according to the power analysis (with 80% power and 5% type I error rate) of the previous studies’ results, the minimum number for the sample was found to be 57patients for anxiety and depression scores in prostate cancer and benign groups. Therefore, we included a total of 204 patients in the current study. The power of this study was found to be 0.665  using variance analysis. The Pearson Correlation test was used between questionnaire scores and the age, PSA level and education level. The Mann-Whitney U test and Pearson Chi-square test were used for univariate analysis between the groups according to histopathologic examination results. Also, the Pearson Correlation test was used for questionnaire scores and age, PSA level, VAS score, presence of clinically significant PCa and education level in the PCa group. Data are given as mean±SD in the tables. Statistical significance was defined as p <0.05.st month) are shown in stmonth. Also, PSA level was positively correlated with HADS-A and HADS-D scores immediately before TRUS-Bx and in postoperative 1stmonth and positive correlation was found between PSS level in thepostoperative 1stmonth and PSA level. In addition, VAS score was positively correlated with HADS-A immediately after TRUS-Bx and postoperative 1st month PSS. Education level was not correlated with any score. Demographic data and questionnaire results for the benign and malignant (PCa) groups according to histopathological examination results after TRUS-Bx are given in A total of 204 patients who met the inclusion criteria consented to participate and completed the questionnaires. Patient’s demographic data are given in There were 52 patients with clinically significant PCa and 10 with clinically insignificant PCa. No significant correlations were found between presence of clinically significant PCa and anxiety and depression scores.TRUS-Bx is a procedure that can cause significant pain and discomfort in a great proportion of patients   . AnxietMen with consistently elevated PSA values may experience psychological distress in relation with the interval of testing, PSA changes, and biopsy results   . PSA isAnxiety may occur in 30.5% of patients with PCa   . AnxietOur study revealed that the patients’ pre-biopsy symptoms disappeared after biopsy, while there was a significant increase in anxiety and depression in patients after the diagnosis of malignancy. We found that our patients were more worried about cancer than the biopsy procedure. Biopsy results caused a significant difference in 30-day post-biopsy related data. STAI TX-1, STAI TX-2, HADS-A, HADS-D and PSS scores were higher in PCa patients compared with those with benign biopsies. We believe that anxiety can be relieved by explaining to the patients that a significant proportion of patients have clinically insignificant cancer diagnosed after cancer screening and the prognosis of these patients is good. In our study group, 10/62 (16.1%) of PCa patients had clinically insignificant PCa and active surveillance was recommended for these patients. Offering an active surveillence protocol or definitive treatment to the patients did not make a significant difference to their anxiety and depression scores.There are some limitations of the current study. Our analyses stratified by biopsy result were based on small numbers and for that reason, should be considered exploratory. Another limitation is that we could not follow the psychological distress of confirmed biopsy in the patient with active surveillance approximately one year after the first biopsy. We are uncertain about the willingness of the patients to decide to repeat the biopsy and to reply to the same repeated questionnaires. Also, it is better to follow-up about the psychological susceptibility to PSA changes in patients with benign biopsy. Despite its limitations, the study assessed the psychological stress of patients who underwent TRUS-Bx and were diagnosed with PCa using a highly specialized questionnaire.We observed that anxiety and depression before prostate biopsy disappeared in the early post-biopsy period and increased again after the diagnosis of prostate cancer. Diagnosis of PCa causes more anxiety and depression than TRUS-Bx itself.