Clinicopathological predictors of repeated recurrence in sinonasal inverted papilloma.

PURPOSE: To evaluate association between clinical and pathological findings and repeated recurrence in sinonasal inverted papilloma. METHODS: Retrospective cohort study conducted at a tertiary care teaching hospital included all patients operated for inverted papilloma from January 2010 to December 2019. Patients were categorized as primary and recurrent cases. Based on disease status at follow-up, they were subcategorized into 'primary with no recurrence' (PnR), 'primary with recurrence' (PwR), 'recurrent with no further recurrence' (RnR), and 'recurrent with further recurrence' (RwR) groups. Data including demography, clinical, endoscopic and pathological findings were collected and analyzed. RESULTS: Increased incidence of pale appearance of lesion in RnR group (p = 0.017), polypoidal appearance in primary group (p = 0.002) and fibrous appearance in the recurrent group (p = 0.002) were statistically significant. Predominant epithelium was combined respiratory and squamous epithelium in primary and recurrent groups and also in RnR group (p = 0.019), while it was squamous (p = 0.024) in RwR group. Epithelial hyperplasia was more common in primary and RnR groups. Oncocytic change, cystic dilatation, microabscess and squamous metaplasia were seen more in recurrent and RnR groups. Cytoplasmic glycogenation was more in recurrent and RwR groups. Stroma was predominantly edematous in all the groups. CONCLUSIONS: Patients with recurrence are younger and present earlier than those with primary disease. Fleshy appearance and pink/red colour of tumour, lining epithelium being squamous and cytoplasmic glycogenation could be considered as features predicting recurrence. Negative predictors of recurrence of IP include pale appearance of tumour, combined respiratory and squamous epithelium lining and squamous metaplasia.

Rhinosporidiosis-Factors predicting disease recurrence.

BACKGROUND: Rhinosporidiosis is a chronic granulomatous disease of the nose caused by Rhinosporidium seeberi. The disease is largely non-amenable to medical therapy and shows high recurrence rates requiring patients to undergo multiple surgeries often resulting in increased morbidity. OBJECTIVE: To analyse the epidemiological, clinical, histopathological characteristics, treatment and outcome in rhinosporidiosis and to identify factors which predispose to recurrence of the disease. PATIENTS/METHODS: Retrospective analysis of data of all patients with a diagnosis of rhinosporidiosis confirmed by histopathology at a tertiary care hospital from 2015 to 2019. RESULTS: There were 42 patients, 40 males and two females, with a mean age of 37.37 years. Disease showed bilateral involvement in 17 (40.48%) patients. Nineteen (45.24%) patients had more than two sites involved at initial presentation. Most patients had nasal cavity involvement followed by nasopharynx. Among the 28 patients who had a follow-up, 12 showed recurrent disease. However, 21 patients were disease free following a revision excision. Involvement of more than two sites was an independent significant factor for recurrence. On univariate analysis, other factors which showed statistically significant odds of developing recurrence were previous surgery (p = .054), involvement of nasal septum (p = .022), middle turbinate (p = .024), nasopharynx (p = .049) and posterior pharyngeal wall (p = .05). Factors which showed significantly less likelihood of developing a recurrence included patients who had less than 12 months duration from first symptom to intervention (p = .016), involvement of less than two sites (p = .0003) and unilateral disease (p = .019). CONCLUSION: Early intervention in rhinosporidiosis especially when the disease is unilateral and involves less than two sites improves the outcome.

Rhinofacial conidiobolomycosis: Clinical and microbiological characterisation and shift in the management of a rare disease.

BACKGROUND: Conidiobolomycosis is a rare tropical rhinofacial fungal infection which has not been well characterised. The available evidence in its management is sparse due to lack of clinical studies and the limited data on antifungal susceptibility patterns. OBJECTIVE: To analyse the clinical manifestations, antifungal treatment and outcomes of patients with conidiobolomycosis and to determine antifungal susceptibility profiles of the isolates. PATIENTS/METHODS: Retrospective analysis of data of all patients with a diagnosis of conidiobolomycosis confirmed by histopathology and culture at a tertiary care hospital from 2012 to 2019 was done. RESULTS: There were 22 patients, 21 males and one female, with a mean age of 37.1 years. Most common presenting symptom was nasal obstruction, found in 20 (90.90%) patients. Patients who presented within 12 months had a better cure rate (85%) compared to those who presented late (67%). Among the 19 patients who had a follow-up, good outcome was seen in 15 of the 17 (88.24%) patients who were on itraconazole or potassium iodide containing regimen. Of the six patients who received additional trimethoprim-sulphamethoxazole (co-trimoxazole), 67% showed good outcome with two patients showing complete cure and two patients still on treatment with significant improvement. High minimum inhibitory concentration (MIC) values were noted for azoles and amphotericin B, whereas co-trimoxazole showed lowest MIC ranges. CONCLUSION: Itraconazole and potassium iodide are reasonable first-line options for the treatment of conidiobolomycosis. Good clinical response to KI and comparatively lower MIC of co-trimoxazole are promising. Further studies are required for developing clinical breakpoints that can predict therapeutic outcomes.

Hydrocortisone metabolism by Staphylococcus: Effects on anti-inflammatory and antimicrobial action.

KEY POINTS: Hydrocortisone 21-hemisuccinate (HCHS) influenced the growth and metabolism of Staphylococcus aureus S. aureus metabolic activity was high and antibiotic susceptibility low at 1.4 mg/mL HCHS S. aureus metabolized HCHS to cortisol and reduced poly(I:C)-induced IL-6 secretion.

Pott's puffy tumor: An unusual complication of rhino-orbito-cerebral mucormycosis.

Objective: To describe clinicoradiological features and surgical outcomes in a series of nine patients with rhino-orbito-cerebral mucormycosis (ROCM) who presented with Pott's puffy tumor (ROCM-PPT). Methods: The records of nine patients with ROCM-PPT seen between March 2020 and December 2021 were analysed. Clinical features, radiology, histopathology, operative findings, management and outcome were noted. Frontal sinus pneumatisation and outflow tract configuration was compared between patients and controls with ROCM and no PPT. Results: ROCM-PPT was diagnosed in 9 of 284 (3.2 %) patients with ROCM seen during the study period. There were six (66.7 %) males and the median age was 54 (IQR 46-60) years. Eight (88.9 %) patients had diabetes mellitus and seven (77.8 %) had been COVID-19 positive. Radiological features of osteomyelitis, subperiosteal abscess formation and dural enhancement were seen in all patients. No significant differences in pneumatisation or frontal sinus outflow tract configuration were noted between patients and controls. All patients underwent a craniectomy with frontal bone debridement and frontal sinus exteriorisation. All patients were treated with anti-fungal agents for several months. All patients had symptomatic improvement at a median follow-up of 21 (IQR 18-23) months. Repeat CT/MRI scans showed disease regression/resolution in six out of eight (75 %) patients with follow-up imaging, and stable disease in two others. Conclusions: ROCM-PPT is a rare, delayed complication of mucormycosis that was seen in larger numbers during the recent COVID-19 pandemic. Aggressive debridement of osteomyelitic bone and antifungal therapy results in a good outcome.

A Comparative Study of Acute Invasive Fungal Sinusitis During the First and Second Waves of the COVID-19 Pandemic.

We aimed to compare the demography, clinical profile, histopathology, fungal culture, radiology, surgery performed, medical therapy and outcomes of patients with acute invasive fungal sinusitis seen during the first and second waves of the COVID-19 pandemic by retrospectively reviewing their case records. Of 238 patients, 43(18.1%) presented during the first wave and 195(81.9%) during the second wave. Patients seen during the first wave were older (p = 0.04) and more likely to have visual impairment (p = 0.004), frozen eye (p = 0.012), altered sensorium (p = 0.007) and stage 3 disease (p = 0.03). Those seen during the second wave were more often COVID-19 positive and had newly diagnosed diabetes mellitus (p = 0.04)and stage 1 disease (p = 0.03). Most patients had a positive culture for Rhizopus species during both waves. Histopathology showed broad aseptate hyphae in all patients but angioinvasion was seen more often during the first wave (p = 0.04). The majority of patients were treated with endoscopic+/- open debridement followed by intravenous amphotericin B and oral posaconazole. While the overall survival rate was similar (first wave 65.1%; second wave 79%; p = 0.106), mortality after discharge was greater during the first wave (11.6% vs 1.5%; p = 0.001). Mortality was higher in patients with stage 3 disease (p = 0.003). Significant differences in clinical presentation, histopathology, radiological stage of disease and post-discharge survival were noted between the two waves of the COVID-19 pandemic, the causes for which were multi-factorial.

Optimizing Surgical Management of Acute Invasive Fungal Sinusitis.

Objective: Early surgical debridement is vital for favorable outcomes in acute invasive fungal sinusitis (AIFS). Our study aimed to propose guidelines with tailored, conservative surgical procedures based on areas of involvement and evaluate their usefulness in avoiding repeated debridement. Methods: This retrospective observational study was conducted on 150 AIFS patients operated on with the proposed surgical guidelines from May to June 2021 at a tertiary care hospital. Data including demography, comorbidities, surgical procedures, revision surgery, and outcome were collected and analyzed. Results: All 150 patients underwent bilateral endoscopic sinonasal debridement. Among them, 108 patients (72%) had current or recent coronavirus disease (COVID) infection. Ninety-two patients (61.3%) required additional procedures based on disease extent. Twenty patients (15.4%) required revision debridement because of progressive or recurrent disease. Mean age of this group was 46.15 (standard deviation ±11.2) years with a strong male predominance (9:1). Seventeen had diabetes mellitus, 12 suffered from active COVID-19 infection and six had received corticosteroids. None of the 31 patients who had recovered from COVID-19 or had no comorbidities required revision surgery. Age, gender, and comorbidities were not significant predictors for revision surgery. Fourteen patients (70%) underwent second surgery within one month of primary surgery. Predominant disease locations were alveolus and palate (55% each), and in 80% the site was uninvolved at primary surgery. The most common revision procedure was inferior partial maxillectomy (60%). At follow-up, all were asymptomatic with no evidence of disease. Conclusion: The proposed surgical guidelines for AIFS allow for adequate surgical debridement with preservation of optimum functional status. Low revision surgery rates and good outcomes with minimal morbidity validate its usefulness.

Short intravenous amphotericin B followed by oral posaconazole using a simple, stratified treatment approach for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis: a prospective cohort study.

OBJECTIVES: To evaluate the efficacy and safety of short-course intravenous amphotericin B followed by sustained release posaconazole tablets for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. METHODS: This prospective, pragmatic study included adults with diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. Patients received short (7-14 days) or long (15-28 days) intravenous antifungal therapy (short intravenous antifungal treatment [SHIFT] or long intravenous antifungal treatment [LIFT], respectively) depending on the presence or absence of brain involvement. All patients received step-down posaconazole tablets, debridement, and glycemic control. The primary outcome was the treatment success at week 14, which was determined by assessing survival and the absence of disease progression through clinical evaluation and nasal endoscopy. Log-binomial regression analysis (risk ratio and 95% CI) was performed to assess factors associated with the primary outcome. RESULTS: Intravenous therapy was administered to 251 participants: SHIFT, 205 (median duration, 13 days); LIFT, 46 (median duration, 22 days). Treatment success at 3 months was 88% (217/248; 95% CI, 83-91%): SHIFT group, 93% (189/203; 89-96%); LIFT group, 62% (28/45; 47-76%). All-cause mortality was 12% (30/251): SHIFT group, 6% (13/205); LIFT group, 37% (17/46). Age (aRR [95% CI]: 1.02 [1.00-1.05]; p 0.027), diabetic ketoacidosis at presentation (2.32 [1.20-4.46]; p 0·012), glycated haemoglobin A1c (1.19 [1.03-1.39]; p 0.019), stroke (3.93 [1.94-7.95]; p 0·0001), and brain involvement (5.67 [3.05-10.54]; p < 0.0001) were independently associated with unsuccessful outcomes. DISCUSSION: Short intravenous amphotericin B with step-down posaconazole tablets should be further studied as primary treatment option for diabetes or COVID-19-associated mucormycosis in randomized controlled trials.

Characteristics of Chronic Rhinosinusitis with Nasal Polyps Based on Allergic Mucin and Fungal Elements in Patients Undergoing Revision Endoscopic Sinus Surgery.

This study sought to document the features in chronic rhinosinusitis with nasal polyp (CRSwNP) patients undergoing revision endoscopic sinus surgery (RESS), based on presence or absence of allergic mucin (AM) and fungal elements (F). A retrospective chart review of RESS cases collected Lund Mackay score (LMS), endoscopic, microbiological, histopathological, surgical and follow-up data of these patients. Patients were categorised into AM + F +, AM + F-, AM-F + and AM-F- subgroups based on the presence or absence of AM and F. The total serum IgE was significantly higher (p > 0.001) in the AM + F + subgroup. Other factors analysed including LMS, duration from previous surgery, comorbidities, degree of inflammation and disease recurrence showed no specific predilection among subgroups. Patients with a retained middle turbinate showed lesser (p = 0.04) recurrence on follow-up. Subgroups of recurrent CRSwNP showed similar characteristics and had further disease recurrence which was independent of allergic mucin and fungal elements. The presence of an intact healthy middle turbinate could reduce early disease recurrence following RESS.

Risk factors associated with the mucormycosis epidemic during the COVID-19 pandemic.

This study was performed to assess the risk factors driving the epidemic of coronavirus disease 2019 (COVID-19)-associated mucormycosis (COVID-Mucor) in India that has accompanied the COVID-19 pandemic, particularly during the second wave. Risk factors were analysed among 164 participants: 132 COVID-Mucor (cases) and 32 non-COVID-Mucor (controls). Data from a prospective cohort study of mucormycosis over a period of 1 year were used. Diabetes mellitus remained a significant risk factor in both groups (97%), while uncontrolled diabetes mellitus (odds ratio (OR) 4.6; P = 0.026) and newly detected diabetes (OR 3.3; P = 0.018) were more common among the cases. Most patients with COVID-Mucor had mild COVID-19. Steroid use, often unwarranted, was highly associated with COVID-Mucor after adjusting for other risk factors (OR 28.4; P = 0.001). Serum ferritin was significantly higher (P = 0.041), while C-reactive protein was not, suggesting that alterations in iron metabolism may predispose to COVID-Mucor. Oxygen was used only in a small minority of patients with COVID-Mucor. The in-hospital mortality in both groups was low. In conclusion, the Indian COVID-Mucor epidemic has likely been driven by a convergence of interlinked risk factors: uncontrolled diabetes mellitus, unwarranted steroid use, and perhaps COVID-19 itself. Appropriate steroid use in patients with severe COVID-19 and screening and optimal control of hyperglycaemia can prevent COVID-Mucor.

Effect of commercial nasal steroid preparation on bacterial growth.

BACKGROUND: Topical budesonide (Pulmicort; AstraZeneca AB, Sodertalje, Sweden) is commonly used in the management of chronic rhinosinusitis (CRS). Although its use is due to its perceived anti-inflammatory effect, studies have suggested that it may also have antibacterial properties. To make the hydrophobic steroid molecule suitable for topical administration, pharmaceutical excipients are used in commercial steroid formulations. Herein we investigated the antibacterial action of commercial budesonide and its excipients. METHODS: Planktonic and biofilm forms of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) were treated with Pulmicort or its excipients at clinically relevant concentrations. Bacterial growth was determined by optical density, resazurin assays, colony-forming unit counts, and Giemsa staining. Minimum inhibitory concentration (MIC) studies assessed excipients' potentiation of antibiotics. Experiments were conducted in triplicate and results analyzed using one-way analysis of variance. RESULTS: There was significant reduction in planktonic and biofilm growth of S aureus and MRSA on exposure to budesonide (p < 0.0001) and its excipients (p < 0.0001). Excipient ethylene diamine-tetraactic acid (EDTA) demonstrated an antibacterial property even at the low concentrations used in topical preparations (p < 0.0001). With amoxicillin, excipients exhibited a potential additive/synergistic effect on MIC, whereas erythromycin and aminoglycosides showed an antagonistic action. CONCLUSION: The commercial product Pulmicort has a direct antibacterial effect on the planktonic and biofilm forms of S aureus and MRSA. This effect is at least in part mediated through the excipient EDTA in the product. Excipients also influenced the antimicrobial activity of antibiotics depending on the bacterial strain and antibiotic tested.

Extent of maxillary sinus surgery and its effect on instrument access, irrigation penetration, and disease clearance.

BACKGROUND: Middle meatal antrostomy (MMA) provides limited access to the anteromedial and inferior aspect of the maxillary sinus (MS) often resulting in residual disease and inflammatory burden. Newer extended procedures, such as mega-antrostomy (Mega-A) and extended modified mega-antrostomy (EMMA), have been developed to address this limitation. This study assesses the effect of varying extent of MS surgery on irrigation penetration and access of instrumentation. METHODS: The MS of 5 fresh-frozen cadavers were sequentially dissected. Irrigation was evaluated with a squeeze bottle (SB) in different head positions and using different volumes of fluid. Surgical reach and visualization were examined using common sinus instruments and different angled endoscopes. A disease simulation was also performed to check for residual debris after instrumentation and irrigations. RESULTS: Irrigation penetration improved as antrostomy size increased (p < 0.0001), with a significant difference observed between the extended procedures and MMA. The effect of the volume was significant for SB (p < 0.0001) but head positions appeared irrelevant (p = 0.613). Overall visualization improved for Mega-A and EMMA. A similar trend was seen for the reach of the instruments to all sinus wall subsites. EMMA facilitated the most removal of "sinus disease" in the disease simulation model when compared with both MMA and Mega-A, due to its reach of the anteroinferior aspects of the maxillary sinus. CONCLUSIONS: High-volume irrigation using SB achieved good sinus penetration, irrespective of head position. Extended MS procedures appear to further increase irrigation penetration as well as surgical access.