A Clinicopathological study of Fungal Diseases in Patients with Chronic Rhinosinusitis and Sinonasal Polyposis

INTRODUCTION: Fungi have been implicated in the etiopathogenesis of chronic rhinosinusitis with nasal polyposis. In an era with AIDS, broad spectrum antibiotic therapy, cytotoxic drugs, steroid therapy and the organ transplantations, fungal infections are becoming increasingly common and very diverse. The most common site of fungal infections in man is the lung with or without haematogenous spread to other organs. But localised fungal infections can also occur in the upper respiratory tract and is more common than was previously suspected. FUNGAL SPECIES: The common fungal infection which affect the nose and sinuses are Candidiasis, Aspergillosis, Phycomycosis, Actinomycosis, Coccidioidomycosis, Histoplasmosis, Cryptococcosis, Blastomycosis, Sporotrichosis and Nocardiosis. FUNGAL SINUSITIS: Fungus is ubiquitous, present in all our surroundings and the air we inhale.Most healthy people do not react to the presence of fungus due to functioning immune system. However, in rare instances,fungus may cause inflammation in the nose and sinuses. Fungal sinusitis may come in different forms, differing in pathology, symptoms, course, severity and the treatment required. CLASSIFICATION OF FUNGAL RHINOSINUSITIS: Fungal Rhinosinusitis is broadly classified into 2 groups 1) INVASIVE, 2) NON INVASIVE INVASIVE diseases include: a) Acute Invasive (Fulminant) Fungal Rhinosinusitis – Mucorales and Aspergillus. b) Granulomatous invasive Fungal rhinosinusitis – A.flavus c) Chronic invasive fungal rhinosinusitis – A.fumigatus NonInvasive diseases include: a) Fungal ball – A.fumigatus, A.flavus, Scedesporium b) Allergic fungal rhino-sinusitis – Bipolaris sp., Curvularia lunata, A.fumigatus. AIMS OF THE STUDY: To study the prevalence of Fungal Diseases in all cases of Sinonasal polyposis and chronic rhino-sinusitis admitted for Functional Endoscopic Sinus Surgery in our Hospital. OBJECTIVES: 1. To find out the prevalence of Fungal Sinusitis in cases of sinonasal polyposis/Chronic rhino-sinusitis. 2. To determine the presence of fungal organisms in Chronic rhinosinusitis associated with nasal polyposis by both KOH mount and fungal culture. 3. To identify the type of fungal sinusitis in sinonasal polyposis/Chronic rhino-sinusitis. 4. To identify the fungal isolates most common in chronic sinusitis and sinonasal polyposis. 5. To study the clinical and pathological manifestations of fungal infections of the nose and paranasal sinuses. 6. To find the association of Fungal sinusitis with Systemic diseases. MATERIALS AND METHODS: Specimen: sinus secretions and Polyps. Sample Size: 156. Patients of all age groups and of either sex who presented with radiologically proven sinusitis with symptoms > 12 weeks duration and undergoing functional endoscopic sinus surgery was included in the study. Patients were interviewed by structured questionnaire after obtaining informed consent. All the patients were also clinically assessed Inclusion Criteria: • All cases of CRS who underwent functional endoscopic sinussurgery in the department of ENT, TVMCH. • All age groups. • Both male & female. Exclusion Criteria: Patients who were on topical or systemic steroid for the past One month before the study period. All cases with characteristic appearance of fungi in DNE and during surgery. Cases with Clinically appearing Malignant Nasal mass and Rhinosporidiosis. Period of study: 2 years. Duration : November 2017 to June 2019. METHODS OF COLLECTION OF DATA. Detailed History taking and clinical examination. Relevant radiological investigations(CTscan). Obtaining a definitive diagnosis with the help of KOH mount and Fungal Culture reports. Sample collection and processing. During my study period , samples of nasal sinus tissue, sinus secretions and allergic mucin from patients undergoing FESS were subjected to mycological culture. The specimen was collected in sterile saline per operatively and taken to the microbiology lab as early as possible and was processed on the sameday. The sample was be subjected to direct microscopy with 10% potassium hydroxide and culture. RESULTS: In the present study 156 patients of chronic rhinosinusitis, majority of the patients were in the age group of 31 – 40 years. followed by 21-30 years.The mean age of the patients affected with fungal rhinosinusitis was 34.5 yrs. Males were predominant (55%) compared to females (45%). Male to female ratio was (1.3:1). The most common symptoms were nasal obstruction 85%, headache 56%, nasal discharge 24%, and sneezing 21%. In this study, 53 patients had nasal polyp 60 had deviated nasal septum, 15 patients had diabetes, 9 had hypertension and 4 had both. In this present study,out of 156 cases of chronic rhinosinusitis, prevalence of fungal rhinosinusitis was found to be 13%. In this study fungal positivity was found in 20 patients by direct examination (KOH mount) or culture In this study majority of the fungi isolated were Aspergillus species (90%) in particular A.flavus. Out of the 18 Aspergillus isolates 13 were Aspergillus flavus and 5 were Aspergillus fumigatus. CONCLUSION: The sinonasal mycotic infection accounts for 13% of chronic rhinosinusitis. The most commonly affected age group are the third and fourth decade. The sex ratio is more or less equal. Fungal sinusitis should be suspected in those patients with CRS presenting with signs and symptoms such as nasal obstruction, nasal polyps, nasal discharge. With the help of histopathological examination of all sinus specimens, CT scan, Diagnostic Nasal Endoscopy thediagnosis of CRS have become easier nowadays. Endoscopic sinus surgery followed by antifungal therapy role is the major treatment of fungal sinusitis. Due to the increased incidence in fungal infections of paranasal sinuses, the Otorhinolaryngolgists should keep fungal infections in their mind during their daily practice. In fungal sinusitis, unilateral involvement of paranasal sinuses is more common. Maxillary sinus is the most commonly affected sinus among all the paranasal sinuses in fungal rhinosinusitis

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant