Metagenomic insights into fungal community composition of the nasopharyngeal region of COVID-19 associated mucormycosis patients from India.

Coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) was reported predominantly from India during the second wave of COVID-19  and has a high mortality rate. The present study aims to understand the fungal community composition of the nasopharyngeal region of CAM-infected individuals and compare it with severe COVID-19 patients and healthy controls. The fungal community composition was decoded by analyzing the sequence homology of the internal transcribed spacer-2-(ITS-2) region of metagenomic DNA extracted from the upper respiratory samples. The alpha-diversity indices were found to be significantly altered in CAM patients (p < 0.05). Interestingly, a higher abundance of Candida africana, Candida haemuloni, Starmerella floris, and Starmerella lactiscondensi was observed exclusively in CAM patients. The interindividual changes in mycobiome composition were well supported by beta-diversity analysis (p < 0.05). The current study provides insights into the dysbiosis of the nasal mycobiome during CAM infection. In conclusion, our study shows that severe COVID-19 and CAM are associated with alteration in mycobiome as compared to healthy controls. However, the sequential alteration in the fungal flora which ultimately leads to the development of CAM needs to be addressed by future studies.

Real World Presentation and Treatment Outcomes with a Predominant Induction Chemotherapy Based Approach in Nasopharyngeal Carcinoma: A Sixteen Year Report from a Teaching Hospital in India.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a rare malignancy in India except in north-eastern states. We present our institutional experience of 16 years highlighting management, outcomes, responses and toxicities. MATERIALS AND METHODS: NPC patients registered at our center during the period of 2000-2015. The primary objective of the study was to assess the overall survival (OS). Secondary outcome included determinations of response rates, progression free survival (PFS) and to assess treatment-related toxicity (CTCAE v4.0). Institute ethics committee approval was obtained prior to initiation of this study. RESULTS: Data was retrieved from complete records of 222 patients out of 390 registered during study period. There were 163 males (73.4%) and 59 females (26.6%) with a male to female ratio of 2.8:1. The median age was 35 years (range 6-73). Only 5.6% (n = 12) presented in early-stage disease (stage I and II) while 89.6% (n = 199) were advanced stage (stage III, IVA, IVB). Five patients (2.2%) presented as metastatic disease. Majority of patients were treated with induction chemotherapy followed by concurrent chemoradiation (CCRT) {76.1%, n = 169}. Relapses were documented in 10.4% patients. 5% patients had loco-regional relapse while distant metastases were seen in 4% patients. The 3-year PFS and OS rates are 60.9% and 68.4%, respectively. Achieving a CR predicted superior OS on multivariate analysis. CONCLUSIONS: NPC is a rare malignancy and majority presented with advanced stages. This data outlines our experience and outcomes with a predominantly induction chemotherapy followed by definitive CCRT based approach.

Factors affecting clinical outcome in COVID-associated rhino-orbito-cerebral mucormycosis (CAROM) patients-An ambispective, single-arm, observational study.

BACKGROUND: COVID-associated Rhino-Orbito-Cerebral Mucormycosis (CAROM) appeared as an epidemic in India during the second wave of the COVID-19 pandemic during the months of March to May 2021. Though many reports have highlighted cross sectional and short-term attributes related to CAROM, long term follow up data is sparse. OBJECTIVE: This report aims to analyze the follow-up outcomes in consecutive patients presenting to us during the epidemic. PATIENTS AND METHODS: This was an ambispective observational analytical study, recruiting the consecutive patients admitted to our tertiary care centre during the period of the CAROM epidemic. The mortality rate during the follow-up and various factors affecting survival were studied using univariable and multivariable statistics with the Stata 14.0 software. RESULTS: Of the 189 patients studied, eight were lost to follow-up. The outcome analysis was performed for the 181 patients. 93.6 % (162/173) of the patients had diabetes. The All-cause mortality was 45 % (81/181), while the ROCM-specific mortality was found to be 24 % (46/181) at a median follow-up of 176 days (IQR: 21-217 days). With univariable analysis, increasing age, higher serum IL-6 levels, presence of additional comorbidities (in addition to Diabetes and hypertension), bilateral disease, skin necrosis, palatal involvement, infratemporal fossa involvement, and impaired vision/ocular movements were found to be associated with increased mortality. However, on multivariable analysis, only 1) increasing age, 2) raised serum IL-6 levels, and 3) bilateral disease were predictive of increased mortality. Surgical debridement (endoscopic, palatal removal, orbital exenteration, neurosurgical intervention) was associated with significantly reduced mortality on both univariable and multivariable analysis. CONCLUSION: Our intermediate-term follow-up data showed advanced age at presentation, raised IL-6 levels, and bilateral sinonasal involvement to be predictive of increased mortality, while surgical debridement is significantly protective from mortality in CAROM patients.

Split-bolus, single-phase contrast enhanced CT: a one-stop shop for invasive fungal sinusitis.

Contrast-enhanced magnetic resonance imaging is considered the imaging modality of choice for invasive fungal sinusitis (IFS); however, it is not feasible to perform emergency CEMRI especially in the setting of COVID-19. The CECT protocol for evaluation of suspected IFS can be modified by using split-bolus, single-phase CT as it provides an optimal soft tissue demonstration of sinonasal disease; extrasinus spread to orbit, and intracranial involvement along with simultaneous opacification of the internal carotid artery and cavernous sinus. The extent of bone erosion can also be well delineated on the multiplanar reconstructions (MPRs) in the bone window. Further a structured reporting format can help provide optimal surgical guidance in cases of IFS.

The Childhood and Adolescent Sleep Evaluation Questionnaire (CASEQ): Development and validation of an ICSD-3-based screening instrument, a community and hospital-based study.

Sleep disorders are common in children and adolescents. Polysomnography is the gold-standard diagnostic method; however, it is a tedious procedure. The objective of the study was to develop a screening questionnaire for sleep problems based on International Classification of Sleep Disorders-3 in children and adolescents, and validate it with clinical evaluation and polysomnography. A questionnaire was developed in English and Hindi with content validation by eight multidisciplinary experts. Respondents were parents of children and adolescents, aged 2-18 years, recruited from a public school and a tertiary care teaching hospital in north India. A subset of these children and adolescents underwent overnight polysomnography and detailed clinical evaluation within 4 weeks of applying the questionnaire. The questionnaire, named Childhood and Adolescent Sleep Evaluation Questionnaire, contains primary questions covering all subgroups of disorders under International Classification of Sleep Disorders-3, and secondary questions on sleep hygiene and comorbidities. The questionnaire was filled by 750 respondents, out of which 100 cases underwent polysomnography and clinical evaluation. The internal consistency in the form of Cronbach's α was 0.8 for the questionnaire. The sensitivity, specificity, positive and negative predictive values for the questionnaire in identifying those with sleep problems compared with detailed clinical and polysomnographic evaluations were 85%, 100%, 100% and 62.5%, respectively. For individual subgroups of disorders, the sensitivity, specificity, positive and negative predictive values varied between 72.7% and 100%, 88.9% and 100%, 62.5% and 100% and 81.6% and 100%, respectively. The Childhood and Adolescent Sleep Evaluation Questionnaire has good psychometric properties, moreover, its simplicity and translatability make it ideal for use at the community and hospital settings.

Human papilloma virus in the etiopathogenesis of allergic nasal polyposis: A prospective study.

PURPOSE: To evaluate and compare the prevalence of high-risk HPV and low-risk HPV types in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and healthy controls. MATERIALS AND METHODS: A prospective cohort study was conducted in a tertiary care hospital on the patients of CRSwNP undergoing surgical management. All patients underwent preoperative endoscopic evaluation and radiological assessment using NCCT of the nose and paranasal sinuses. The severity of the disease was graded using the Lund-Mackay score on NCCT. All patients underwent endoscopic polypectomy and the sample of tissues was sent for HPV DNA detection using Hybrid Capture II® technique. The clinicopathological characteristics of HPV positive and negative patients were compared. RESULTS: Sixty cases and 20 controls were included in the study. All controls were negative for HPV DNA. 27 patients (45%) had the presence of HPV DNA, out of which 23 had only LR-HPV and 1 had only HR-HPV types. Three patients had both HR-HPV and LR-HPV subtypes. There was a significant difference between the cases and controls for the presence of HPV DNA (p < 0.001). However, the patients with HPV-positive DNA in the nasal specimen did not differ significantly from HPV-negative patients in age, gender, or severity of the disease. CONCLUSIONS: Human papillomaviruses may play a significant role in the etiopathogenesis of CRSwNP, however, do not impact the degree of sinus involvement.

Covid-19-associated rhino-orbito-cerebral mucormycosis (CAROM) in Delhi: Demographics and risk factors in a single-centre consecutive cohort of 200 inpatients.

Background There was a dramatic rise in the incidence of rhino-orbito-cerebral mucormycosis associated with the 2021 Covid-19 wave in India. We aim to document the demographic characteristics and risk factors of a consecutive cohort of inpatients with Covid-19-associated rhino-orbito-cerebral mucormycosis (CAROM) during the surge of April-June 2021. Methods We included all patients of CAROM treated at our tertiary referral facility from 1 April to 14 June 2021. We prospectively gathered details with regard to Covid-19 illness and treatment, CAROM presentation, comorbid conditions and risk factors. Results Our prospective cohort consisted of 200 consecutive patients, of which 146 (73%) patients tested positive on the Covid-19 RT-PCR test at presentation. CAROM occurred concurrent with the Covid-19 infection in 86%, and delayed CAROM after seeming recovery from Covid-19 was seen in 14%. Covid-19 was classified as mild, moderate and severe in 54%, 33% and 13%. The surge of CAROM followed the population peak of Covid-19 infections by about 3 weeks. Advanced disease at presentation was frequent with ocular involvement in 56.6% (111/196) and central nervous system involvement in 20% (40/199). One or more comorbid conditions were identified in 191/200 (95.5%) patients. The dominant associations were with diabetes (189/200; 94.5%) and uncontrolled hyper-glycaemia (122/133; 91.7%), recent steroid use (114/ 200; 57%), which was often considered as inappropriate in dosage or duration, lymphopenia (142/176; 80.7%), and increased ferritin levels (140/160; 87.5%). No evidence supported the role of previous oxygen therapy or previous nasal swab testing as risk factors for CAROM. Conclusion The inpatient volumes of CAROM were noted to parallel the Covid-19 incidence curve by about 3 weeks. Covid-19 infection may directly predispose to CAROM by way of lymphopenia and increased ferritin levels. Uncontrolled hyperglycaemia is identified as a near-invariable association. Recent steroid use is noted as very frequent and was often received in excess of treatment advisories.

Topical lignocaine anaesthesia for oropharyngeal sampling for COVID-19.

OBJECTIVES: To ascertain if topical lignocaine application in oropharynx prior to swab sampling to test for COVID-19 improves a patient's comfort and to assess its effect on the swab sample taken to conduct the RT-PCR. METHODS: Adult patients testing positive on the RT-PCR COVID-19 test were sampled again within 48 h after administering topical oropharyngeal anaesthesia. Patients were asked to rate their discomfort on a visual analog scale (VAS) for both sample A and B. A qualitative real-time RT-PCR for detection of SARS-CoV-2 RNA, was performed, and the cycle threshold value (Ct), used as a surrogate marker for the viral load, was measured for the sample taken without lignocaine (sample A) and the sample taken post-lignocaine application (sample B). The difference in Ct values of both the groups was checked for any statistical significance using paired t-test. Wilcoxon signed rank test was used on VAS scores to determine any significant decrease in discomfort. RESULTS: Forty patients were included in the study. Twenty-nine patients (72.5%) reported the procedure to be more comfortable post-lignocaine application. Median (IQR) discomfort on VAS decreased from 7 (1) to 5 (2) after lignocaine use, which was statistically significant (p < 0.05). Mean Ct value for sample A was 17.21 ± 5.25 and for sample B was 18.44 ± 4.8 (p > 0.05), indicating a non-significant effect of lignocaine on SARS-CoV-2 concentration in the sample. CONCLUSION: Topical lignocaine, while improving the comfort of the procedure of oropharyngeal sampling for patient did not alter the SARS-CoV-2 viral load that was detected in nasal and oropharyngeal samples taken together.

Prevalence of hearing loss in India.

Background Despite abundant literature, a clear and coherent understanding of hearing loss (HL) in India is limited by the wide disparity in studies. Methods We did a review of published peer-reviewed journal articles. Studies reporting the prevalence and degree of HL in India from 1980 to 2020 were included. Information was gathered on the population characteristics, methodology applied and the prevalence of hearing impairment. The data were analysed to identify trends and at-risk sections of population in various categories. Results Four hundred and forty studies were identified after a database search; 29 full-length articles were selected for final analysis. Using a 3-step screening protocol, hearing impairment (abnormal auditory brainstem response/auditory steady state response) in neonates ranged between 1.59 and 8.8 per 1000 births. Among 'at risk' neonates, it ranged from 7 to 49.18 per 1000 births. In children the prevalence of HL was 6.6% to 16.47%. Otitis media was the most common cause of HL in children. Community-based studies (all ages) reported prevalence of HL between 6% and 26.9% and prevalence of disabling HL between 4.5% and 18.3%. Rural areas and elderly showed a higher prevalence of hearing impairment. Conclusion Despite India's improving health indices, hearing disability remains persistently high. It is a major contributor to the loss of personal potential and a financial strain for the individual and the country. A large-scale multicentric study to identify the degree and type of HL, social awareness campaigns, widespread neonatal screening, strengthening treatment facilities and well-funded rehabilitation programmes can counter the rising prevalence of hearing impairment.

Revisiting rhino-orbito-cerebral acute invasive fungal sinusitis in the era of COVID-19: pictorial review.

COVID-19 patients have been found to have an increased incidence of superadded fungal infections because of multiple factors such as impaired cell-mediated immunity, immunosuppressive therapy, and coexistent diabetes mellitus. Recently, there has been a significant rise in the COVID-19-associated mucormycosis and aspergillosis cases involving the sinonasal cavity and the lungs. Rhino-orbito-cerebral acute invasive fungal rhinosinusitis (AIFR) is a potentially life-threatening, invasive fungal infection. Early diagnosis followed by prompt medical management and surgical intervention is crucial for patient survival. The role of cross-sectional imaging (CT/MRI) is not only to suggest a diagnosis of invasive fungal sinusitis but also to delineate the complete extent of disease. Mapping the extent of orbital and intracranial disease has prognostic as well as management implications, as involvement of these sites marks a worse prognosis. A stepwise approach to evaluation of imaging of AIFR along with a pictorial depiction of the key imaging findings is presented.

p16 Immunoexpression in sinonasal and nasopharyngeal adenoid cystic carcinomas: a potential pitfall in ruling out HPV-related multiphenotypic sinonasal carcinoma.

AIMS: Adenoid cystic carcinoma (AdCC) is frequent in the sinonasal region. The recently described human papilloma virus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) histopathologically resembles solid AdCC, but has a better outcome. Thus, clinical and pathogenetic differences between HMSC and sinonasal AdCC necessitate their distinction. We conducted this study to assess p16 immunoexpression in previously diagnosed AdCC cases, and to identify HMSC cases in p16 immunopositive cases. METHODS AND RESULTS: Cases diagnosed as sinonasal and nasopharyngeal AdCC were retrieved. Histomorphological features were reviewed. Immunohistochemistry (IHC) for p16 was performed. HPV testing was performed in p16-positive cases by mRNA in-situ hybridisation (mRNA ISH) and polymerase chain reaction (PCR) assay. MYB rearrangement was assessed by fluorescence in-situ hybridisation. One hundred and two AdCC cases were retrieved. Six cases (5.9%) showed diffuse p16 positivity. HPV mRNA ISH and PCR were negative in p16-positive cases. Two cases showed MYB rearrangement. p16-positive cases were composed of basaloid cells demonstrating a cribriform pattern, at least focally. The predominant pattern was cribriform in three and solid in three cases. One case showed two distinct components: keratinising squamous cell carcinoma and cribriform AdCC. Other morphological patterns seen were tubular, reticular, epithelial-myoepithelial carcinoma-like, and glomeruloid, forming a minor component of the tumour area. CONCLUSIONS: p16 staining alone, even when diffuse and strong, cannot be used as a surrogate for HPV testing to distinguish sinonasal AdCC from HMSC. p16 IHC should be accompanied by more specific methods, such as mRNA ISH, so as not to erroneously diagnose HMSC over sinonasal AdCC, bearing in mind the highly aggressive nature of the latter.

Consensus & Evidence-based INOSA Guidelines 2014 (First edition).

Obstructive sleep apnoea (OSA) and obstructive sleep apnoea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences amongst the general public as well as the majority of primary care physcians across India is poor. This necessiated the development of the INdian initiative on Obstructive Sleep Apnoea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health & Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep related symptoms or comorbidities or ≥ 15 such episodes without any sleep related symptoms or comorbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents and high risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography (PSG) is the "gold standard" for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioural measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.

Perioperative complications of cochlear implant surgery in children.

Cochlear implant is a commonly performed surgery for hearing loss in pre-school and school children. However, data on anesthesia management and anesthesia-related complications are sparse. We retrospectively reviewed the data of our institute from January, 2007 to December, 2012. Medical records and anesthesia charts of all the patients who had undergone cochlear implant under general anesthesia between this period were reviewed. Information related to the demographic profile, preoperative evaluation, anesthetic techniques, and perioperative complications were collected and analyzed. A total of 190 patients underwent cochlear implant surgery for pre-lingual (175) and post-lingual (15) deafness. General endotracheal anesthesia with inhalational agents was used in all the cases. Difficult intubation was encountered in three patients. Anesthesia-related complications were laryngospasm at extubation (4.73 %), emergence agitation (2.63 %), and postoperative nausea and vomiting (1.05 %). Major surgical complications were CSF leak without meningitis (3.15 %), device migration/failure (1.05 %), and flap infection (1.57 %). Cochlear implant under general anesthesia in small children is safe and anesthesia-related complications were minimal. Surgical complications, although more frequent, were predominantly minor and self-limiting.

Consensus & evidence-based INOSA Guidelines 2014 (first edition).

Obstructive sleep apnoea (OSA) and obstructive sleep apnoea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences amongst the general public as well as the majority of primary care physcians across India is poor. This necessiated the development of the INdian initiative on Obstructive sleep apnoea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health & Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep related symptoms or co-morbidities or ≥ 15 such episodes without any sleep related symptoms or co-morbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents and high risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography (PSG) is the "gold standard" for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioural measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.

Multimodality management of locoregionally extensive Marjolin ulcer: a case report and review of the literature.

BACKGROUND: Marjolin ulcer (MU) is an aggressive cutaneous malignancy that commonly occurs in those with a chronic wound such as post-burn scar. CASE REPORT: A 20-year-old male who sustained a flame burn over the scalp at 3 months of age developed a nonhealing ulcer over the burn scar 20 years later, which was treated with adequate surgical margins with adjuvant mold brachytherapy. Two months after completion of that treatment, he developed parotid nodal metastasis with positron emission tomography (PET)-positive bilateral cervical, supraclavicular, right suboccipital, and mesenteric lymph nodes that were treated with concurrent chemoradiation. One month later, the patient developed an ulcerative lesion involving the left parotid region with PET showing infiltration of the parotid gland, but with resolution of other previous sites of uptake. The patient was treated surgically with radical parotidectomy with elective neck dissection and reconstruction with locoregional flap. At 6-month follow-up, the patient developed extensive locoregional recurrence and distant metastasis and was started on oral metronomic therapy. The patient was alive with stable disease at 3-month follow-up after initiation of palliative chemotherapy. CONCLUSION: Despite timely multimodality therapy, MU may present with a hostile clinical course with a short disease-free interval and early recurrence.

Novel Therapeutic Strategies of Non-Invasive Brain Stimulation and Nanomedicine in Pediatric Cerebral Palsy Patients.

Infantile central palsy (CP) is caused due to damage to the immature developing brain usually before birth, leading to altered topography and biochemical milieu. CP is a life-limiting disorder, which causes changes in sensory, motor, cognitive, and behavioral functioning. Understanding its pathophysiology is complex, and current therapeutic modalities, oral medication, surgical treatment, physical therapy, and rehabilitation provide minimal relief. As the brain is plastic, it has an inherent capacity to adapt to altered activity; thus, non-invasive brain stimulation (NIBS) strategies, like repetitive transcranial magnetic stimulation, which can modulate the neuronal activity and its function, may lead to recovery in CP patients. Further, in recent years, nanomedicine has shown a promising approach in pre-clinical studies for the treatment of central nervous system disorder because it can cross the blood-brain barrier, improve penetration, and provide sustained release of the drug. The review focuses on the principles and mechanisms of various NIBS techniques used in CP. We have also contemplated the effect of rehabilitation and nanomedicine in CP children, which will definitely lead to advancing our diagnostic as well as therapeutic abilities, in a vulnerable group of little ones.

Quality of life and swallowing outcomes following major glossectomy: A prospective single-center experience.

BACKGROUND: There exists a lacuna in the structured reporting of swallowing dysfunction and quality of life (QoL) outcome following major glossectomy. METHODS: Prospective cohort study to assess the swallowing dysfunction and QoL following STG (subtotal glossectomy) or NTG (near total glossectomy) over a 6-month period using FEES and PAS scale, MDADI, and FACT-HN. RESULTS: Twenty-four patients were available for analysis. The pre- and post-adjuvant evaluation revealed a statistically significant improvement in the composite MDADI and FACT-HN scores. Subscale analysis of FACT-HN scores revealed maximum deficit in the head and neck cancer-specific score domain followed by functional domain and social well-being domain, with serial improvement noted in the post-adjuvant setting. CONCLUSION: This study showed serial improvement in terms of swallowing dysfunction although social and functional well-being domains related to QoL continued to reveal major deficits. Better outcomes were seen with preservation of bilateral base of tongue and mandible.