Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi.

BACKGROUND: In this phase 2 randomised placebo-controlled clinical trial in patients with COVID-19, we hypothesised that blocking mineralocorticoid receptors using a combination of dexamethasone to suppress cortisol secretion and spironolactone is safe and may reduce illness severity. METHODS: Hospitalised patients with confirmed COVID-19 were randomly allocated to low dose oral spironolactone (50 mg day 1, then 25 mg once daily for 21 days) or standard of care in a 2:1 ratio. Both groups received dexamethasone 6 mg daily for 10 days. Group allocation was blinded to the patient and research team. Primary outcomes were time to recovery, defined as the number of days until patients achieved WHO Ordinal Scale (OS) category ≤ 3, and the effect of spironolactone on aldosterone, D-dimer, angiotensin II and Von Willebrand Factor (VWF). RESULTS: One hundred twenty patients with PCR confirmed COVID were recruited in Delhi from 01 February to 30 April 2021. 74 were randomly assigned to spironolactone and dexamethasone (SpiroDex), and 46 to dexamethasone alone (Dex). There was no significant difference in the time to recovery between SpiroDex and Dex groups (SpiroDex median 4.5 days, Dex median 5.5 days, p = 0.055). SpiroDex patients had significantly lower D-dimer levels on days 4 and 7 (day 7 mean D-dimer: SpiroDex 1.15 µg/mL, Dex 3.15 µg/mL, p = 0.0004) and aldosterone at day 7 (SpiroDex 6.8 ng/dL, Dex 14.52 ng/dL, p = 0.0075). There was no difference in VWF or angiotensin II levels between groups. For secondary outcomes, SpiroDex patients had a significantly greater number of oxygen free days and reached oxygen freedom sooner than the Dex group. Cough scores were no different during the acute illness, however the SpiroDex group had lower scores at day 28. There was no difference in corticosteroid levels between groups. There was no increase in adverse events in patients receiving SpiroDex. CONCLUSION: Low dose oral spironolactone in addition to dexamethasone was safe and reduced D-dimer and aldosterone. Time to recovery was not significantly reduced. Phase 3 randomised controlled trials with spironolactone and dexamethasone should be considered. TRIAL REGISTRATION: The trial was registered on the Clinical Trials Registry of India TRI: CTRI/2021/03/031721, reference: REF/2021/03/041472. Registered on 04/03/2021.

Sensitivity of liquid-based cytology in the diagnosis of mucormycosis in COVID-19 treated patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) infection caused by the novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is associated with a wide range of disease patterns, ranging from mild to life-threatening pneumonia. COVID-19 can be associated with a suppressed immune response and/or hyperinflammatory state due to cytokine storm. Reduced immunity, combined with steroid usage to prevent cytokine storm along with various pre-existing co morbidities can prove to be a fertile ground for various secondary bacterial and fungal infection, including mucormycosis. Diagnosis of mucor is a challenging task given high negativity rate of various detection methods. While histopathology is considered the gold standard, the acquisition of necessary tissue biopsy specimens requires invasive procedures and is time consuming. METHOD: In this study various methods of mucor detection, like conventional cytopathology (CCP), liquid-based cytology (LBC, BD SurepathTM ), potassium hydroxide mount (KOH) preparation, culture and histopathology were analysed. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for various methods. RESULTS: This study showed that LBC has sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 72.4%,100%,100% and 38.4% respectively. CONCLUSION: This study showed that, liquid-based cytology (LBC) can be a rapid and effective alternative to histopathology in mucor diagnosis.

Outcomes among 10,314 hospitalized COVID-19 patients at a tertiary care government hospital in Delhi, India.

A significant proportion of patients with coronavirus disease 2019 (COVID-19) require timely hospitalization to reduce the risk of complications and mortality. We describe the trends of the age and gender stratified outcomes among hospitalized COVID-19 patients with moderate to severe illness at the largest dedicated tertiary care COVID-19 government hospital in New Delhi, India. A retrospective cohort study through secondary data analysis from in-patient hospital data of patients admitted from April 1 to November 15, 2020 was conducted. The data of 10,314 laboratory-confirmed patients with COVID-19 was analyzed, of which 8899 (86.28%) were discharged after recovery, and 1415 (13.72%) died. The mean (SD) age of the hospitalized patients was 46.43 (18.74) years (n = 10,309) including 6031 (58.50%) male and 4278 (41.50%) female patients (n = 10,309). On bivariate analysis, increasing age was associated with significantly higher odds of mortality in both gender (p < .001). The mortality rate in female patients was lower (11.92%) compared with male patients (15.75%) (p = .675). However, elderly women had the highest odds of mortality (p < .001), indicating the possible role of delayed health seeking behavior, secondary to familial, and social neglect. Mortality in the patients with COVID-19 also occurred early after admission suggesting rapid deterioration, delayed reporting by patients, or their late referral from other health facilities. However, the overall statewide recovery rate showed steady improvement since the onset of the pandemic. In contrast, the recovery rate among the moderate-severe cases that were hospitalized at this tertiary care center during the same period reflected a lower nonspecific zigzag pattern indicating limited effectiveness of the COVID-19 treatment regimens.

Sensorineural Hearing Loss in Unilateral Mucosal Type of Chronic Otitis Media.

Sensorineural hearing loss is relatively well established in the squamosal chronic otitis media. However, its association with mucosal COM is still debated. The present study aimed at evaluating the prevalence of sensorineural hearing loss in unilateral mucosal COM. The study was conducted at a tertiary care hospital in New Delhi, and 60 patients with unilateral mucosal chronic otitis media were recruited. Pure tone thresholds were ascertained for air and bone conduction in an acoustically treated room and matched against certain patient and disease characteristics. In this study, the combined prevalence of SNHL/Mixed Hearing loss in mucosal COM was found to be 8.3%. A statistically significant association between SNHL/Mixed HL was seen in the 40-50-year age group (p-0.004). Prevalence with a disease duration of more than 10 years was 33% (p-0.019). All the patients who presented with SNHL/Mixed HL had an actively discharging ear. 80% of the patients who presented with SNHL/Mixed HL had large perforations. SNHL/Mixed HL prevalence of 28.6% was found in smokers, compared to 5.7% in non-smokers (p-0.039). The risk of developing SNHL/Mixed HL increased with increasing patients' age, disease duration, and size of the perforation and smokers.

Chronic Alcohol Use Associated Encephalopathy With a Nearly Identical Presentation to Normal Pressure Hydrocephalus.

We present the case of a 52-year-old male who arrived at the Emergency Department after several ground-level falls in the past month. He complained of urinary incontinence, mild confusion, headaches, and appetite loss in the past month as well. Brain computed tomography (CT) and magnetic resonance imaging (MRI) were performed, which showed enlarged ventricles with moderately prominent cortical atrophy and no acute abnormalities. It was decided to conduct a cisternogram study with serial scans. The study showed a type IIIa cerebrospinal fluid (CSF) flow pattern at 24 hours. At the 48- and 72-hour marks, the study displayed an absence of radiotracer activity within the ventricles, while all the activity was concentrated within the cerebral cortices. These findings successfully ruled out normal pressure hydrocephalus (NPH) due to the highly specific indication of normal CSF circulation pattern. The patient was treated with thiamine and advised to quit drinking, as well as return for follow-up in one month as an outpatient for a repeat brain CT.

Comparison of Trans-septal Suturing Technique With Polyvinyl Alcohol Sponge-Based Nasal Packing for Hemostasis in Septoplasty.

Introduction Despite the theoretical advantages of bleeding control, there is increased morbidity in postoperative pain, sleep disturbance, allergy, toxic shock syndrome, and mucosal injury with the nasal packing in septoplasty procedure for deviated nasal septum. Trans-septal suturing after septoplasty has been advocated as an effective alternative to conventional nasal packing. The current study aims to compare the frequency of subjective symptoms, such as postoperative nasal pain, nasal bleeding, postnasal drip, sleep disturbance, dysphagia, headache, and epiphora between the trans-septal suturing technique and nasal packing in septoplasty surgery. Methods We prospectively recruited all adult septoplasty patients for a one-year duration. Trans-septal nasal suturing was done for hemostasis after septoplasty in the case group. Anterior nasal packing after septoplasty was performed in the control group. The postoperative subjective symptoms were evaluated, such as postoperative nasal pain, nasal bleeding, postnasal drip, sleep disturbance, dysphagia, headache, and epiphora. Procedure-related complications were compared between the two groups. Results A total of 50 patients were recruited for the study (25 in each group). The postoperative symptoms evaluation suggested that the number of patients with postoperative pain was significantly higher in the control group on both occasions. Besides pain, a significantly higher number of patients in the control group had symptoms of nasal bleeding, postnasal drip, sleep disturbance, dysphagia, headache, and epiphora. Conclusion Trans-septal suture technique is an effective alternative to nasal packing with a low risk of nasal pain, bleeding, postnasal drip, epiphora, headache, dysphagia, and sleep disturbance. In addition, there is a low risk of complications like nasal bleeding, septal hematoma, septal perforation, and synechiae formation. The only disadvantage of trans-septal suturing compared to PVA-coated nasal packing is the increase in the operative time.

Fine needle aspiration cytology of primary thyroid non-hodgkins lymphoma: Experience from a tertiary care center of North India.

Presentation: Twelve cases of Primary Thyroid Non-Hodgkin's Lymphoma (PT-NHL) were retrieved from the records suspected or diagnosed as NHL on fine needle aspiration cytology (FNAC) over a period of nine years from 2010-2018. During this period 5236 patients underwent thyroid FNAC;of these 685 cases were diagnosed under Bethesda Caregory V and VI. Thyroid NHL constituted 0.23 % of all thyroid FNA (12/5236 cases)and 1.7% (12/685) of all thyroid malignancies. Patients ranged in age from 40-61 years with Female:Male 7:5. All patients presented with thyroid enlargement (5-14 cms), and were of two months to five years duration. Patients had history of tobacco intake (smoking/chewing)in nine cases (75%). Thyroid function tests showed hypothyroidism in four (33%), positive antithyroid antibodies in three (25%) and; two cases(16.7%) were known cases of Hashimotos thyroiditis with follow up. Cytological Findings: Eight cases (66.7%) had monomorphic large cell morphology,other four had mostly intermediate cell types (33.3%). A panel of immunocyto/ histochemistry (ICC/ IHC) showed CD 19 and CD 20 positivity in all cases;sixof these could be correlated on Flow cytometry (FC) with expression of FMC7, CD20, CD19 with kappa light chain restriction (5) and Lambda (1). FC findings corroborated completely with IHC on biopsy sections. The final diagnosis were Diffuse large B cell Lymphoma (DLBCL,8) and MALT- Lymphoma(4). The follow up was available in DLBCL (4) and MALT- Lymphoma (1). CHOP therapy were given in all patients followed by radiotherapy in DLBCL; one patient of DLBCL died following pulmonary complications, rest are well and alive on follow-up. Discussion: PT-NHL is rare in India. DLBCL is the commonest histological type reported. In the present study, tobacco exposure has shown strong association. Combined FNAC-FC provide definitive diagnosis and thus can replace histopathology reducing turn around time. Conclusion: FNAC -FC provides a definitive diagnosis and thus can reduce turnaround time.

Nasopharyngeal Carcinoma With Bilateral Breast Metastasis: A Report of an Elusive Case.

Nasopharyngeal carcinoma is a prevalent head and neck cancer, especially in Southeast Asia. Although its potential for distant metastasis is well established, metastasis to the breast has seldom been reported. To the best of our knowledge, this is the fourth report of a case of nasopharyngeal carcinoma metastasizing to bilateral breasts. A 35-year-old patient presented with left nasal obstruction, epistaxis, and a palpable mass in her left breast, without any cervical or axillary lymph nodal enlargement. Radiological examination with contrast-enhanced computed tomography scan and magnetic resonance and imaging of breast revealed the presence of enhancing mass lesions in bilateral breasts. Histopathology of the nasal mass was suggestive of undifferentiated nasopharyngeal carcinoma. Breast fine needle aspiration revealed an abundance of metastatic squamous cells. Immunohistochemistry examination was positive for chromogranin A, synaptophysin, and cluster of differentiation-56, confirming the diagnosis of a primary nasopharyngeal malignancy metastasizing to bilateral breasts. Differentiation between metastatic disease and a coexisting second primary is imperative for planning appropriate treatment and defining the further outcomes.

Differentiation of Benign From Malignant Sinonasal Masses Using Diffusion Weighted Imaging and Dynamic Contrast Enhanced Magnetic Resonance Imaging.

BACKGROUND: The sinonasal region is affected by a variety of neoplasms. A differentiation between benign and malignant masses is essential both for management and prognostication. Morphological analysis often does not allow this differentiation. OBJECTIVES: This article aims to assess the value of advanced MRI (diffusion [DWI] and dynamic contrast enhanced MRI [DCE-MRI]) in differentiation of benign and malignant sinonasal masses. METHODS: This prospective study included 40 patients with sinonasal masses who underwent advanced MR on 3T MR scanner. The lesions were analyzed based on morphological characteristics, qualitative, quantitative diffusion parameters, and time signal intensity curves. Apparent diffusion coefficient (ADC) values were acquired using b values of 50 and 1000 s/mm2. The accuracy of DWI, DCE-MRI, and combined DWI/DCE-MRI in differentiating benign from malignant sinonasal masses were analyzed. RESULTS: Perineural extension and growth pattern of the tumor were the best morphological discriminators. Mean ADC values for benign and malignant lesions were 1.675 ± 0.561 and 0.903 ± 0.405 × 10-3 mm2/sec, ,respectively. ROC revealed that ADC cutoff value of 1.005 × 10-3 mm2/sec provided an accuracy of 92.5% in differentiating benign from malignant masses (P value <.01). On excluding the benign vascular masses (Juvenile Nasopharyngeal Angiofibroma and hemangioma), the time signal intensity curve showed 78% accuracy (P value <.001). The highest diagnostic performance was achieved by combining DWI and DCE-MRI (95% accuracy). CONCLUSION: DWI has higher accuracy than DCE-MRI. Quantitative DWI is preferable over qualitative DWI. Accuracy of DCE-MRI can be increased by excluding vascular masses with characteristic imaging features. DWI and DCE-MRI have the highest accuracy when used in combination than either of them alone in differentiating benign from malignant sinonasal masses.

Perceived usefulness of trauma audit filters in urban India: a mixed-methods multicentre Delphi study comparing filters from the WHO and low and middle-income countries.

OBJECTIVE: To compare experts' perceived usefulness of audit filters from Ghana, Cameroon, WHO and those locally developed; generate context-appropriate audit filters for trauma care in selected hospitals in urban India; and explore characteristics of audit filters that correlate to perceived usefulness. DESIGN: A mixed-methods approach using a multicentre online Delphi technique. SETTING: Two large tertiary hospitals in urban India. METHODS: Filters were rated on a scale from 1 to 10 in terms of perceived usefulness, with the option to add new filters and comments. The filters were categorised into three groups depending on their origin: low and middle-income countries (LMIC), WHO and New (locally developed), and their scores compared. Significance was determined using Kruskal-Wallis test followed by Wilcoxon rank-sum test. We performed a content analysis of the comments. RESULTS: 26 predefined and 15 new filter suggestions were evaluated. The filters had high usefulness scores (mean overall score 9.01 of 10), with the LMIC filters having significantly higher scores compared with those from WHO and those newly added. Three themes were identified in the content analysis relating to medical relevance, feasibility and specificity. CONCLUSIONS: Audit filters from other LMICs were deemed highly useful in the urban India context. This may indicate that the transferability of defined trauma audit filters between similar contexts is high and that these can provide a starting point when implemented as part of trauma quality improvement programmes in low-resource settings.

Electrocardiogram Signals Denoising Using Improved Variational Mode Decomposition.

BACKGROUND: Electrocardiogram (ECG) plays a vital role in the analysis of heart activity. It can be used to analyze the different heart diseases and mental stress assessment also. Various noises, such as baseline wandering, muscle artifacts and power line interface disturbs the information within the ECG signal. To acquire correct information from ECG signal, these noises should be removed. METHODS: In the proposed work, the improved variational mode decomposition (IVMD) method for the removal of noise in ECG signals is used. In the proposed method, the weighted signal amplitude integrated over the timeframe of the ECG signal varies the window size during decomposition. Raw ECG data are extracted from 10 subjects and ECG data are also taken from the MIT BIH database for the proposed method. RESULTS: The performance comparison of traditional variational mode decomposition (VMD) and the proposed technique is also calculated using mean square error, percentage root mean square difference, signal to noise ratio and correlation coefficient. The extracted highest signal to noise ratio (SNR) value of acquired ECG signals using traditional VMD is 42db whereas highest value of signal to noise ratio (SNR) using improved VMD (IVMD) is 83db. CONCLUSION: The proposed IVMD technique represented better performance than traditional VMD for denoising of ECG signals.

Design and rationale of an intelligent algorithm to detect BuRnoUt in HeaLthcare workers in COVID era using ECG and artificiaL intelligence: The BRUCEE-LI study.

BACKGROUND: There is no large contemporary data from India to see the prevalence of burnout in HCWs in covid era. Burnout and mental stress is associated with electrocardiographic changes detectable by artificial intelligence (AI). OBJECTIVE: The present study aims to estimate the prevalence of burnout in HCWs in COVID-19 era using Mini Z-scale and to develop predictive AI model to detect burnout in HCWs in COVID-19 era. METHODS: This is an observational and cross-sectional study to evaluate the presence of burnout in HCWs in academic tertiary care centres of North India in the COVID-19 era. At least 900 participants will be enrolled in this study from four leading premier government-funded/public-private centres of North India. Each study centre will be asked to recruit HCWs by approaching them through various listed ways for participation in the study. Interested participants after initial screening and meeting the eligibility criteria, will be asked to fill the questionnaire (having demographic and work related with Mini Z questionnaire) to assess burnout. The healthcare workers will include physicians at all levels of training, nursing staff and paramedical staff who are involved directly or indirectly in COVID-19 care. The analysis of the raw electrocardiogram (ECG) data and development of algorithm using convolutional neural networks (CNN) will be done by experts. CONCLUSIONS: In Summary, we propose that ECG data generated from the people with burnout can be utilized to develop AI-enabled model to predict the presence of stress and burnout in HCWs in COVID-19 era.

Impending Rupture of Internal Carotid Artery Aneurysm Mimicking Peritonsillar Abscess.

Extracranial carotid artery aneurysms are rare but important entity. Impending rupture of such aneurysms can lead to catastrophic hemorrhage, airway compromise and may prove fatal. The authors report a case of true aneurysm of cervical internal carotid artery in a four-year-old girl who presented with fever and swelling of neck and oropharynx. High clinical suspicion is required to differentiate aneurysm from peritonsillar and parapharyngeal abscess as incision and drainage can prove fatal. Securing airway beforehand and timely embolization has led to the favorable outcome in the present case.

Largest De Novo Parapharyngeal Pleomorphic Adenoma: A Rare Case Removed Via Minimal Access Approach.

Parapharyngeal tumors are relatively rare tumors of head and neck. In general, pleomorphic adenoma is one of the most common benign tumor of the parapharyngeal region. Various approaches have been described in the literature for removal of parapharyngeal tumor with mandibulotomy generally carried out for large tumors. Here, we describe removal of a large parapharyngeal pleomorphic adenoma transcervically without mandibulotomy which subsequently turned out to be one of the largest ever reported in the literature and describe how large tumors of parapharyngeal can be removed with minimal invasive approach with mandibulotomy kept as a backup thereby avoiding complications associated with mandibulotomy.

Classical chemotherapy: mechanisms, toxicities and the therapeutic window.

Chemotherapy can be best used by understanding the principles of pharmacology, tumor biology, cellular kinetics and drug resistance. Here we try to focus on the major classes of chemotherapeutic drugs, their mechanisms of action, toxicities; and the therapeutic window.

Neoadjuvant and adjuvant chemotherapy with doxorubicin and docetaxel in locally advanced breast cancer.

Fifty patients with histologically confirmed stage III breast cancer were enrolled in this study of doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 intravenously infused over 1 hour every 21 days with granulocyte colony-stimulating factor for 4 cycles. This was followed by surgery (mastectomy or lumpectomy) and 4 more cycles of doxorubicin/docetaxel postoperatively, then radiation and tamoxifen as indicated. Forty-six of the 50 patients (92%) completed neoadjuvant chemotherapy, and 38 patients (76%) completed adjuvant chemotherapy. Clinical response (defined as > 50% decrease in size of tumor) was achieved after 2 cycles in 37 patients (74%) and after 4 cycles in 42 of the 46 patients (91%) who finished neoadjuvant chemotherapy. Pathologic complete response (pCR; no pathologic invasive cancer) at the primary site was obtained in 7 of 46 patients (15%); 11 had no residual gross disease but did have microscopic persistence or microscopic complete response (mCR), for a combined pCR and mCR of 18 of 46 patients (39%). No treatment-related deaths occurred, but 3 patients died during treatment: 1 from progressive disease, 1 from a gastrointestinal bleeding, and 1 from unexplained sudden cardiac death. Dose-limiting toxicities were hematologic (grade 3 neutropenia in 5 patients and grade 4 in 23 patients). Congestive heart failure developed in 4 of 50 patients (8%), with a mean decrease in left ventricular ejection fraction (LVEF) of 20% in affected patients and 1 asymptomatic decrease in LVEF of 25%. At last follow-up, 10 patients had died of progressive disease, and 1 each from sudden cardiac death and lower gastrointestinal bleeding. In locally advanced breast cancer, neoadjuvant doxorubicin/docetaxel is a very active regimen that achieved pCR of 15% and a combined pCR and mCR of 39%, for an overall clinical response rate of 91%. Adjuvant chemotherapy was complicated by dropouts and congestive heart failure. This regimen should be used with close monitoring of cardiac function.

Non-syndromic hearing impairment in India: high allelic heterogeneity among mutations in TMPRSS3, TMC1, USHIC, CDH23 and TMIE.

Mutations in the autosomal genes TMPRSS3, TMC1, USHIC, CDH23 and TMIE are known to cause hereditary hearing loss. To study the contribution of these genes to autosomal recessive, non-syndromic hearing loss (ARNSHL) in India, we examined 374 families with the disorder to identify potential mutations. We found four mutations in TMPRSS3, eight in TMC1, ten in USHIC, eight in CDH23 and three in TMIE. Of the 33 potentially pathogenic variants identified in these genes, 23 were new and the remaining have been previously reported. Collectively, mutations in these five genes contribute to about one-tenth of ARNSHL among the families examined. New mutations detected in this study extend the allelic heterogeneity of the genes and provide several additional variants for structure-function correlation studies. These findings have implications for early DNA-based detection of deafness and genetic counseling of affected families in the Indian subcontinent.