Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Clinical and Mycologic Characteristics of Emerging Mucormycosis Agent Rhizopus homothallicus.

We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02-0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03-16], itraconazole [0.03-16], posaconazole [0.03-8], and isavuconazole [0.03-16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus.

Drug-induced sleep endoscopy-continuous positive airway pressure (DISE-CPAP), a newer modality to choose the right candidates for CPAP.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy is recommended for moderate-to-severe obstructive sleep apnea (OSA). We aimed to investigate whether or not combining drug-induced sleep endoscopy (DISE) with CPAP titration may inform more appropriate pressure settings. MATERIALS AND METHODS: A sleep CPAP titration study and DISE-CPAP treatment were performed on consecutive subjects with moderate-to-severe OSA under controlled sedation using bispectral monitoring. Video recordings of dynamic changes in UA with CPAP pressure ranges of 5 to 25 cm were assessed in accordance with the VOTE classification. The 95th percentile (95th PC) pressure of the CPAP titration trial was compared to optimal pressure for alleviating UA blockage. RESULTS: We included 30 subjects (mean age 37.5, 17% women). All showed UA collapse at more than one level, with more than 80% of them collapsing completely at the levels of the velum and oropharynx. At the velum, 90% of subjects experienced improvement with CPAP. At the oropharynx, 75% of subjects experienced improvement with CPAP. The mean pressure and standard deviation (SD) of the 95th PC of the CPAP titration was 14.3 (3.5) cmH2O, while the pressure required to partially or fully open the airway (best possible pressure) was 16.1 (3.9) cmH2O; mean (SD) difference, 1.9 (2.2); P ≤ 0.001. The limits of agreement between the CPAP 95th pressure and the ideal pressure were - 6.32 to + 2.52. CONCLUSIONS: The palate and lateral pharynx were more affected by CPAP than the hypopharynx. Most of the time, the mean 95th PC CPAP titration pressure was lower than the mean optimal pressure needed to alleviate the collapse.

Serum PTH at 4 h after total thyroidectomy as a predictor of hypocalcemia: a prospective time frame analysis in search of evidence.

INTRODUCTION: There has not been a universal agreement about the timings and the threshold level of PTH that can accurately predict the risk of hypocalcemia. Our study aimed to investigate the changes in the serum PTH levels at various time intervals and correlate it with the development of subsequent hypocalcemia. MATERIALS AND METHODS: All patients had a pre-operative serum PTH done and were again assessed intra-operatively, at 4 h, 24 h, 72 h, and 1 month after the thyroid surgery. Absolute serum PTH value at various time points, absolute change in serum PTH values compared to pre-operative level, and relative change (percentage change) in serum PTH values compared with pre-operative levels were used to predict post-operative Hypocalcemia. RESULTS: 49 patients were included in the study. The sensitivity and negative predictive value was 100% for serum PTH at 4 h. There was a statistically significant difference between the groups that required calcium supplementation versus the group that did not require it. The maximum relative reduction in serum PTH value with respect to the pre-operative level occurred at 4 h in the calcium supplement required group which was 82.5%. Use of combination of 4 h serum PTH and relative change at 4 h yielded the best results. CONCLUSION: A combination of absolute serum PTH level at 4 h and the relative decline in serum PTH at 4 h has the highest diagnostic accuracy. The use of this combined parameter helps to reliably predict patients who would require supplementation.

Satellite Epidemic of Covid-19 Associated Mucormycosis in India: A Multi-Site Observational Study.

BACKGROUND: Sudden upsurge in cases of COVID-19 Associated Mucormycosis (CAM) following the second wave of the COVID-19 pandemic was recorded in India. This study describes the clinical characteristics, management and outcomes of CAM cases, and factors associated with mortality. METHODS: Microbiologically confirmed CAM cases were enrolled from April 2021 to September 2021 from ten diverse geographical locations in India. Data were collected using a structured questionnaire and entered into a web portal designed specifically for this investigation. Bivariate analyses and logistic regression were conducted using R version 4.0.2. RESULTS: A total of 336 CAM patients were enrolled; the majority were male (n = 232, 69.1%), literate (n = 261, 77.7%), and employed (n = 224, 66.7%). The commonest presenting symptoms in our cohort of patients were oro-facial and ophthalmological in nature. The median (Interquartile Range; IQR) interval between COVID diagnosis and admission due to mucormycosis was 31 (18, 47) days, whereas the median duration of symptoms of CAM before hospitalization was 10 (5, 20) days. All CAM cases received antifungal treatment, and debridement (either surgical or endoscopic or both) was carried out in the majority of them (326, 97.02%). Twenty-three (6.9%) of the enrolled CAM cases expired. The odds of death in CAM patients increased with an increase in HbA1c level (aOR: 1.34, 95%CI: 1.05, 1.72) following adjustment for age, gender, education and employment status. CONCLUSION: A longer vigil of around 4-6 weeks post-COVID-19 diagnosis is suggested for earlier diagnosis of CAM. Better glycemic control may avert mortality in admitted CAM cases.

Neuropsychological Differences between the Unilateral and Bilateral Tinnitus Participants with Normal Hearing.

INTRODUCTION: This paper attempts to describe the neuropsychological differences between subgroups of tinnitus with normal hearing. METHODS: The study compared 150 normal-hearing participants with and without tinnitus in the 18-55 age-group. The participants completed nine neuropsychological tests, namely, Rey's auditory verbal learning test (RAVLT), Rey complex figure test (RCFT), digit vigilance test (DVT), Verbal N-back test (N Back), controlled oral word association test (COWA), animal names test (ANT), digit symbol substitution test (DSST), Wechsler digit span test (DST), and Stroop test. RESULTS: Poor verbal memory was demonstrated by a unilateral tinnitus group (p = 0.0001) for the total RAVLT score, immediate score, delayed recall, hits, and omissions). Significant deficits were observed in working memory functioning by the unilateral and bilateral tinnitus participants (p < 0.001) for one-back and two-back hit and error scores). In addition, there was a significant impairment in the auditory attention of single-sided tinnitus participants (p < 0.03, 0.02). Selective attention was affected in bilateral tinnitus participants (p < 0.05). DISCUSSION/CONCLUSION: Tinnitus, whether unilateral or bilateral, has an effect on working memory. The RAVLT and DST results, on the other hand, demonstrated that unilateral tinnitus suffers from significant deficits in auditory memory and attention, whereas bilateral tinnitus suffers from selective attention issues. When treating individuals with unilateral and bilateral tinnitus, these findings must be addressed.

Serum iron indices in COVID-19-associated mucormycosis: A case-control study.

BACKGROUND: Whether dysregulated iron metabolism is associated with COVID-19-associated mucormycosis (CAM) remains unknown. Herein, we compare the serum iron indices in COVID-19 subjects with and without mucormycosis. METHODS: We conducted a case-control study enrolling COVID-19 participants with and without mucormycosis. We compared the baseline serum iron indices (iron, ferritin, total iron-binding capacity [TIBC], unsaturated iron-binding capacity and percentage transferrin saturation) between CAM cases and COVID-19 controls. Additionally, we performed a multivariate logistic regression analysis to assess whether any iron indices are associated with CAM. RESULTS: We enrolled 28 CAM cases (mean age 53.6 years old; 78.6% men) and 26 controls (mean age 57.2 years old; 73.1% men). Rhino-orbital (±cerebral) mucormycosis (85.7%) was the most clinical presentation. Diabetes mellitus was more frequent in the cases than controls (75% vs. 42.3%; p = .015). Hypoxaemia during COVID-19 illness was more common in controls than cases. The mean serum iron values (33 vs. 45 µg/dl, p = .03) and TIBC (166.6 vs. 201.6 µg/dl, p = .003) were significantly lower in CAM cases than controls. On multivariate analysis, we found a lower TIBC (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.95-0.99) and diabetes mellitus (OR 5.23; 95% CI, 1.21-22.68) to be independently associated with CAM after adjusting for serum iron, ferritin and glucocorticoid therapy. The case fatality rate of CAM was 73.9%. The iron indices were not significantly different between CAM survivors and non-survivors. CONCLUSIONS: The CAM is associated with lower TIBC levels than COVID-19 subjects without mucormycosis, suggesting dysregulated iron metabolism in its pathogenesis. Further studies are required to confirm our preliminary observations.

As the virus sowed, the fungus reaped! A comparative analysis of the clinico-epidemiological characteristics of rhino-orbital mucormycosis before and during COVID-19 pandemic.

BACKGROUND: The sudden surge of mucormycosis cases which happened during the second wave of COVID-19 pandemic was a significant public health problem in India. OBJECTIVES: The aim of this study was to analyse the clinico-epidemicological characteristics of the mucormycosis cases to determine the changes that had occurred due to COVID-19 pandemic. METHODOLOGY: A retrospective cross-sectional study was conducted at the Department of Otolaryngology Head and Neck Surgery, PGIMER, Chandigarh, India. Patients diagnosed with rhino-orbital mucormycosis were categorised into the following groups: Pre-pandemic(May 2019 to April 2020), Pandemic Pre-epidemic (May 2020 to April 2021) and Epidemic (1 May 2021 to 12 July 2021). The epidemiological, clinical and surgical data of all the patients were retrieved from the hospital records and analysed. RESULTS: The epidemic period had 370 cases, compared with 65 during pandemic period and 42 in the pre-pandemic period. Diabetes mellitus was seen in 87% of cases during epidemic period, 92.9% in the pre-pandemic period and 90.8% in the pre-pandemic pre-epidemic period. The proportion of patients suffering from vision loss, restricted extra-ocular movements, palatal ulcer and nasal obstruction was higher in the pre-epidemic groups, and the difference was significant (p, <.01). There was no history of oxygen use in 85.9% of patients and no steroid use in 76.5%. The death rates were the lowest during epidemic (10%). CONCLUSION: COVID-19 has caused a statistically significant increase in the number of mucormycosis infections. The mortality and morbidity which showed an increase during the first wave of COVID-19 decreased significantly during the epidemic period.

Serum glucose-regulated protein 78 (GRP78) levels in COVID-19-associated mucormycosis: results of a case-control study.

BACKGROUND: In experimental models, the expression of glucose-regulated protein 78 (GRP78) in endothelial cells played a role in the pathogenesis of mucormycosis. However, the role of GRP78 in COVID-19-associated mucormycosis (CAM) has not been studied. We hypothesized that serum GRP78 levels are elevated in subjects with CAM. OBJECTIVE: To compare the serum GRP78 levels in subjects with CAM and COVID-19 controls without mucormycosis. DESIGN AND SETTING: We performed a hospital-based, case-control study between 1 April 2021 and 31 May 2021. PARTICIPANTS: We enrolled 24 subjects each of CAM and COVID-19 subjects without mucormycosis. We also measured serum GRP78 levels in ten healthy controls. EXPOSURE: The primary exposure studied was serum GRP78 concentration, estimated using a commercially available ELISA kit in stored serum samples. RESULTS: We found the mean ± standard deviation (SD) serum GRP78 levels significantly higher (p = 0.0001) among the CAM (374.3 ± 127.3 pg/mL) than the COVID-19 (246.4 ± 67.0 pg/mL) controls. The proportion of subjects with an abnormal GRP78 level (> mean [184.8 pg/mL] plus two SD [23.2 pg/mL] of GRP78 from healthy participants) was 87.5% and 45.8% in the CAM group and COVID-19 controls, respectively. Serum GRP78 level was independently associated with CAM (odds ratio 1.011; 95% confidence interval [1.002-1.019]) after adjusting for diabetes mellitus and hypoxemia during acute COVID-19. CONCLUSION: Serum GRP78 levels were significantly higher in CAM than in COVID-19 controls. Further studies are required to the role of GRP78 in the pathogenesis of CAM.

Is there an association between zinc and COVID-19-associated mucormycosis? Results of an experimental and clinical study.

BACKGROUND: The enormous increase in COVID-19-associated mucormycosis (CAM) in India lacks an explanation. Zinc supplementation during COVID-19 management is speculated as a contributor to mucormycosis. We conducted an experimental and clinical study to explore the association of zinc and mucormycosis. METHODS: We inoculated pure isolates of Rhizopus arrhizus obtained from subjects with CAM on dichloran rose Bengal chloramphenicol (DRBC) agar enriched with (three different concentrations) and without zinc. At 24 h, we counted the viable colonies and measured the dry weight of colonies at 24, 48 and 72 h. We also compared the clinical features and serum zinc levels in 29 CAM cases and 28 COVID-19 subjects without mucormycosis (controls). RESULTS: We tested eight isolates of R arrhizus and noted a visible increase in growth in zinc-enriched media. A viable count percentage showed a significantly increased growth in four of the eight isolates in zinc-augmented DRBC agar. A time- and concentration-dependent increase in the mean fungal biomass with zinc was observed in all three isolates tested. We enrolled 29 cases of CAM and 28 controls. The mean serum zinc concentration was below the reference range in all the subjects and was not significantly different between the cases and controls. CONCLUSIONS: Half of the R arrhizus isolates grew better with zinc enrichment in vitro. However, our study does not conclusively support the hypothesis that zinc supplementation contributed to the pathogenesis of mucormycosis. More data, both in vitro and in vivo, may resolve the role of zinc in the pathogenesis of CAM.

Feasibility of Using Posterior Auricular Artery as Landmark for Identification of Facial Nerve Trunk in Parotid Surgery: A Cadaver Study.

INTRODUCTION: Despite good surgical knowledge of the anatomy of parotid gland and meticulous surgical technique, the incidence of facial palsy in parotid surgeries is up to 26.7% transient and 1.7% complete facial palsy(1). The risk of facial palsy increases further in malignant and revision cases. METHOD: Superficial parotidectomy was done in 14 cadaveric hemi faces in 10 cadavers. Posterior auricular artery and its stylomastoid branch was dissected and facial nerve trunk was identified in all cases. The relationship of posterior auricular artery along with its stylomastoid branch with the facial nerve trunk was studied and recorded. RESULT: Posterior auricular artery was found running inferior to the facial nerve trunk in 12 cadaveric dissection while the posterior auricular artery was found crossing below the main trunk of facial in 2 cadaver dissection. The average distance between PAA and facial nerve trunk was 7 mm (2-14 mm) Stylomastoid artery was found arising from Posterior auricular artery in 12 of 14 and it was found running medial to the facial nerve trunk in all the 8 cadavers. CONCLUSION: Post auricular artery can be used as another landmark for identification of the main trunk of facial nerve in parotid surgeries.

Perception of Tinnitus Handicap And Stress Across Age Groups in Normal Hearing.

INTRODUCTION: This research was conducted to investigate the severity of tinnitus, its impact on subject's daily, personal and emotional life, which varies widely across the age groups. METHODOLOGY: Sample population of 60 unilateral tinnitus subjects with normal hearing between the age ranges of 15-55years were divided into four age groups. Tinnitus severity was measured using tinnitus severity index, impact of tinnitus on daily life was documented through tinnitus handicap inventory and the stress levels through perceived stress scale. RESULTS: A high frequency tinnitus was observed in age group of 56-65years, in contrast to noise like tinnitus in subjects aged 15-25years. The tinnitus was found to be most handicapping (38-56; moderate handicap) in Group 4(56-65years), the perceived stress levels were also falling in very high range (21 and over). Tinnitus severity index did not show any significant difference between the Group 1:15-25yrs, Group 2: 26-40yrs, Group 3:41-55yrs, and however group 4(56-65 yrs) did report with mild severity. The outcomes of present study demonstrated that elderly subjects certainly require modifications in the test protocols and referrals to address to their significant responses to tinnitus.

Assessment of Clinical and Histological Changes in the Skin Paddle of Pectoralis Major Myocutaneous Flap in Intraoral Reconstruction: A Prospective Cohort Study.

PURPOSE: This study was carried out to characterize the clinical and histological changes in the cutaneous portion of the transferred pedicled pectoralis major myocutaneous flaps used in intraoral reconstruction in patients with head and neck malignancy. METHODS: This was a prospective cohort study carried out from July 2016 to 2018. All patients underwent ablative surgery for oropharyngeal cancers and primary reconstruction with pedicled pedicled pectoralis major myocutaneous flaps. The intraoral flaps were examined for color, texture, presence of hair, chronic inflammatory changes, and ulceration. At 12 months, incisional biopsies were taken from the skin paddle of the intraoral flap and contralateral normal buccal mucosa, and flap histology was compared with that of the contralateral buccal mucosa. RESULTS: Twenty patients were included in the final analysis (M/F, 4:1; mean ± SD age, 51.38 ± 6.76 years). Fourteen flaps resembled oral mucosa, 3 had a mixed appearance of both skin and mucosa, and 3 had appearance of normal skin at 1 year follow-up. The epidermis and stratum corneum were retained in all the flap biopsies; however, severe attenuation was noted in 7 patients (had mucosal appearance) but was significantly different from oral mucosa(P = 0.0003). Cutaneous appendages were found in all the flap epithelia. Thirteen flaps showed grossly attenuation, of which 11 patients had a gross appearance resembling oral mucosa and 2 had a mixed appearance. The biopsies showed varied degree of chronic changes like desquamation in around 35% (7 patients), hyperkeratosis in 35% (7 patients), and chronic candidiasis in 30% (6 patients). CONCLUSIONS: Although the intraorally transferred flaps demonstrate a morphological appearance similar to oral mucosa, there is a histological preservation of skin elements and architecture.

Analysis of volumetric and dosimetric changes in mid treatment CT scan in carcinoma nasopharynx: implications for adaptive radiotherapy.

OBJECTIVE: Carcinoma of nasopharynx is a radiosensitive tumor and therapeutic response during radiation treatment can result in dosimetric variations in the delivered dose to the tumor and critical organs. This study was done to evaluate the volumetric and dosimetric changes seen in tumor tissue and organs at risk in a mid treatment planning scan and its implications for adaptive replanning. Twenty patients of locally advanced carcinoma nasopharynx were evaluated. All patients were started on treatment with a baseline treatment plan on SIB-VMAT. To evaluate volumetric and dosimetric changes during treatment, a mid treatment CT scan (MTS) was taken at the 17th fraction of treatment and compared with the baseline planning CT scan (BS). Adaptive treatment plans were generated on the MTS and further treatment was continued on the adaptive plans. The mean weight loss observed at the 17th fraction of treatment was 3.4 ± 2.6 kg(Mean±S.D). The mean neck diameter at C2 level was 14.19±1.02 and 13.29 ± 1.14 cm in the BS and MTS respectively (p=0.001). The GTV 70 volume showed a 29.16% volume loss. The mean doses received by the right and left parotids were 25.45±0.98 and 24.64±3.8 Gy in the baseline treatment plan and 33.21±11.29 (p=0.054) and 31.76±8.44 Gy respectively in the MTS (p=0.016) The mean weight loss showed a statistically significant correlation with increase in the right parotid(p=0.043) and left parotid doses(p=0.024). Weight loss during treatment combined with volume changes in target tissues mandate routine adaptive replanning while treating carcinoma nasopharynx.

A prospective multicenter study on mucormycosis in India: Epidemiology, diagnosis, and treatment.

Mucormycosis due to Mucorales is reported at large numbers in uncontrolled diabetics across India, but systematic multicenter epidemiological study has not been published yet. The present prospective study was conducted at four major tertiary care centers of India (two in north and two in south India) during 2013-2015 to compare the epidemiology, treatment strategies and outcome of mucormycosis between the two regions. Molecular techniques were employed to confirm the identity of the isolates or to identify the agent in biopsy samples. A total of 388 proven/probable mucormycosis cases were reported during the study period with overall mortality at 46.7%. Uncontrolled diabetes (n = 172, 56.8%) and trauma (n = 31, 10.2%) were the common risk factors. Overall, Rhizopus arrhizus (n = 124, 51.9%) was the predominant agent identified, followed by Rhizopus microsporus (n = 30, 12.6%), Apophysomyces variabilis (n = 22, 9.2%) and Rhizopus homothallicus (n = 6, 2.5%). On multivariate analysis, the mortality was significantly associated with gastrointestinal (OR: 18.70, P = .005) and pulmonary infections (OR: 3.03, P = .015). While comparing the two regions, majority (82.7%) cases were recorded from north India; uncontrolled diabetes (n = 157, P = .0001) and post-tubercular mucormycosis (n = 21, P = .006) were significantly associated with north Indian cases. No significant difference was noted among the species of Mucorales identified and treatment strategies between the two regions. The mortality rate was significantly higher in north Indian patients (50.5%) compared to 32.1% in south India (P = .016). The study highlights higher number of mucormycosis cases in uncontrolled diabetics of north India and emergence of R. microsporus and R. homothallicus across India causing the disease.

DNA methylation regulated microRNAs in HPV-16-induced head and neck squamous cell carcinoma (HNSCC).

INTRODUCTION: Epigenetic modifications have been reported to play an important role in regulating gene expression and these modifications become critical when they have a role in controlling another important layer of epigenetic regulation namely microRNAs. In the present study, we have identified the microRNAs that may be regulated by promoter DNA methylation and histone acetylation in Human papilloma virus-positive head and neck squamous cell carcinoma. METHODOLOGY: HPV-negative cell line (UPCI:SCC-116) and HPV-16 +ve cell line (UPCI:SCC-090) were treated with methylation inhibitor (5-aza-2'-deoxycytidine, AZA) and acetylation inhibitor (Trichostatin-A, TSA), followed by micro-array analysis. The differentially expressed miRNAs were validated in control (n = 10), HPV-16 +ve (n = 30), and HPV -ve (n = 30) HNC, TCGA (n = 529) tissue samples, and two HPV -ve (SCC116 and Hacat) and two HPV +ve (SCC090 and SiHa) cell lines. Methylation-specific PCR (MSP) and chromatin immunoprecipitation assay (CHIP) were performed to validate their regulation. In silico and in vitro analyses of identified miRNAs were done to study putative pathways they target and their possible role in carcinogenesis. RESULTS: Among 10 miRNAs specifically up-regulated in microarray analysis of AZA-treated SCC090 cells, we observed significantly decreased expression of hsa-miR-181c-5p, hsa-miR-132-5p, hsa-miR-658 in HPV +ve HNC cohort, TCGA tissue samples, and cell lines as compared to their HPV -ve counterpart, and their promoter region also possesses CpG islands. MSP and analysis of TCGA data (MethHC) revealed increased frequency of methylation at the promoter of hsa-miR-132-5p that is negatively correlated with its expression. In TSA-treated SCC090 cells, out of 7 miRNAs, two namely Hsa-miR-129-2-3p and Hsa-miR-449a were found to be up-regulated as compared to HPV -ve cells. However, the levels of enrichment by anti-acetyl-H3 and anti-acetyl-H4 were significantly low in cell lines compared to respective controls and both were up-regulated in HPV +ve compared to HPV -ve TCGA tissue samples. In silico analysis revealed hsa-miR-132-5p targeted canonical ß-catenin/wnt pathway and modulation of down-stream genes of the pathway was observed on over-expression/inhibition of hsa-miR-132-5p. CONCLUSION: This study suggests the role of epigenetic modifications in regulating expression of miRNAs in HPV +ve HNSCC.

Surgery for post-traumatic facial paralysis: are we overdoing it?

PURPOSE: Early facial nerve decompression is recommended for cases of post-traumatic facial palsy on the basis of ENoG with degeneration > 95%. There is still a dispute in the literature concerning the role and timing of surgery versus conservative treatment in such cases. This study has been planned to evaluate the outcome of conservative management in traumatic facial paralysis with regard to type of trauma, onset, and electrodiagnostic tests. METHODS: A prospective cohort study included 39 patients with post-traumatic facial palsy. All patients underwent ENoG, nerve stimulation test, HRCT temporal bone and Schirmer's test. The patients received intravenous methylprednisolone 1 gm/day for 5 days or oral prednisolone 1 mg/kg in tapering doses for 3 weeks. Follow-up was done at 4, 12 and 24 weeks after the treatment. Surgical exploration was limited to patients showing no improvement after 12 weeks. Facial nerve function was evaluated by the HBFNS and FEMA grading systems. RESULTS: Among the 39 patients in the study [5 women and 34 men; mean (SD) age, 33.5 (11.37) years], facial nerve recovery with conservative treatment alone was noted in 31 patients. The first signs of clinical recovery were noted in 27 patients by 4 weeks, in 31 patients by 12 weeks. Seven patients required surgical exploration. At 24 weeks, 31 patients recovered to House-Brackmann grade I/III and 1 patient to grade IV. 19 of 26 patients with longitudinal fractures had grade I/III recovery, whereas all 6 patients with transverse fracture recovered on conservative treatment. CONCLUSIONS: Patients with incomplete facial palsy are candidates for conservative management. It is justified to try conservative management in patients with complete facial paralysis for up to 3 months even in cases where ENoG and NET suggest poor prognosis. The presence of sensorineural hearing loss or transverse fracture at presentation does not suggest a poor prognosis for improvement.