The Utility of the Ultrasonographic Characteristics in Differentiating Between Malignant and Tuberculous Mediastinal Lymphadenopathy During EBUS-TBNA.

BACKGROUND: Ultrasonographic characteristics may help differentiate between benign and malignant lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). There is limited data on the utility of various ultrasonographic lymph node features to differentiate between malignant and tuberculous mediastinal lymphadenopathy. METHODS: We studied the various EBUS ultrasonographic lymph node characteristics (size, shape, margins, heterogeneous echotexture, calcification, central hilar structure, lymph node conglomeration, central intranodal vessel, and coagulation necrosis sign) from our available EBUS-TBNA database. RESULTS: We extracted 1086 subjects [547 with tuberculosis (TB) and 539 with malignant diagnosis]. Comparing the 2 groups (multivariate analysis), presence of central hilar structure (8.2% vs. 2.6%), coagulation necrosis sign (37.5% vs. 13.7%), lymph node conglomeration (30.5% vs. 7.2%), calcification (5.1% vs. 1.5%), and distinct margins (83.5% vs. 69.8%), were significantly more common in TB ( P <0.05). On the other hand, malignant lymph nodes were larger and more likely to show the presence of a central intranodal vessel (20% vs. 15.8%, P =0.04, multivariate analysis). The absence of lymph node conglomeration had the highest overall diagnostic accuracy (0.61) for the differentiation between malignant and tuberculous lymph nodes. CONCLUSION: Sonographic lymph node characteristics may help differentiate malignant and tuberculous mediastinal lymphadenopathy. Contrary to previously published literature, we observed coagulation necrosis sign, heterogeneous echotexture and absent central intranodal vessel, more commonly in TB than malignant nodes. These findings from a TB endemic setting are different from other settings, where the prevalence of lung cancer is high in patients undergoing EBUS-TBNA.

Selection of Ideal Reference Genes for Gene Expression Analysis in COVID-19 and Mucormycosis.

Selection of reference genes during real-time quantitative PCR (qRT-PCR) is critical to determine accurate and reliable mRNA expression. Nonetheless, not a single study has investigated the expression stability of candidate reference genes to determine their suitability as internal controls in SARS-CoV-2 infection or COVID-19-associated mucormycosis (CAM). Using qRT-PCR, we determined expression stability of the nine most commonly used housekeeping genes, namely, TATA-box binding protein (TBP), cyclophilin (CypA), ß-2-microglobulin (B2M), 18S rRNA (18S), peroxisome proliferator-activated receptor gamma (PPARG) coactivator 1 alpha (PGC-1α), glucuronidase beta (GUSB), hypoxanthine phosphoribosyltransferase 1 (HPRT-1), ß-ACTIN, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in patients with COVID-19 of various severities (asymptomatic, mild, moderate, and severe) and those with CAM. We used statistical algorithms (delta-CT [threshold cycle], NormFinder, BestKeeper, GeNorm, and RefFinder) to select the most appropriate reference gene and observed that clinical severity profoundly influences expression stability of reference genes. CypA demonstrated the most consistent expression irrespective of disease severity and emerged as the most suitable reference gene in COVID-19 and CAM. Incidentally, GAPDH, the most commonly used reference gene, showed the maximum variations in expression and emerged as the least suitable. Next, we determined expression of nuclear factor erythroid 2-related factor 2 (NRF2), interleukin-6 (IL-6), and IL-15 using CypA and GAPDH as internal controls and show that CypA-normalized expression matches well with the RNA sequencing-based expression of these genes. Further, IL-6 expression correlated well with the plasma levels of IL-6 and C-reactive protein, a marker of inflammation. In conclusion, GAPDH emerged as the least suitable and CypA as the most suitable reference gene in COVID-19 and CAM. The results highlight the expression variability of housekeeping genes due to disease severity and provide a strong rationale for identification of appropriate reference genes in other chronic conditions as well. IMPORTANCE Gene expression studies are critical to develop new diagnostics, therapeutics, and prognostic modalities. However, accurate determination of expression requires data normalization with a reference gene, whose expression does not vary across different disease stages. Misidentification of a reference gene can produce inaccurate results. Unfortunately, despite the global impact of COVID-19 and an urgent unmet need for better treatment, not a single study has investigated the expression stability of housekeeping genes across the disease spectrum to determine their suitability as internal controls. Our study identifies CypA and then TBP as the two most suitable reference genes for COVID-19 and CAM. Further, GAPDH, the most commonly used reference gene in COVID-19 studies, turned out to be the least suitable. This work fills an important gap in the field and promises to facilitate determination of an accurate expression of genes to catalyze development of novel molecular diagnostics and therapeutics for improved patient care.

Patient profile and comparison of three diagnostic criteria for cardiac sarcoidosis in a tuberculosis endemic population.

BACKGROUND: Cardiac sarcoidosis (CS) is an underdiagnosed and life-threatening condition. Histopathological diagnosis is difficult due to the risks and variable diagnostic yield of endomyocardial biopsy. OBJECTIVES: To study the clinical profile and compare the diagnostic criteria of CS in a cohort of sarcoidosis. METHODS: A retrospective review of the Sarcoidosis database (375 patients) was performed to identify patients with CS. Demographic and clinical details were retrieved. We applied the available diagnostic criteria for the diagnosis of CS: The World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG), Heart Rhythm Society (HRS), and Japanese Ministry of Health and Welfare (JMHW) criteria. RESULTS: Out of the 375 patients, 15 (4%) were identified with CS. The median age was 41 years, and 53% were female. The most common symptoms were breathlessness, palpitation, and fatigue in 80%, 53.3%, and 46.6% of patients, respectively. Tuberculin positivity (≥ 10mm induration) was seen in 26.6%. 80% and 53.3% of the patients had abnormal ECG and 2D echocardiography findings, respectively. Six patients had a history of Ventricular tachycardia (40%). LV Ejection fraction was reduced in 12 subjects (80%). Cardiac-MRI showed late gadolinium enhancement in 53.3%. A definitive histopathological diagnosis for sarcoidosis was established in 86.6% (13/15) patients. Of the 15, all satisfied JMHW criteria and WASOG criteria (12 (80%) at least probable category, 3 (20%) possible CS), and 13 (86.6%) met HRS criteria for a diagnosis of CS. CONCLUSION: In a cohort of 375 patients with sarcoidosis in a tuberculosis endemic setting, 4% were diagnosed with cardiac sarcoidosis. Histopathological diagnosis may be obtained by sampling from extracardiac sites. JMHW and WASOG criteria perform equally well in TB endemic settings.

Utility of Elastography for Differentiating Malignant and Benign Lymph Nodes During EBUS-TBNA: A Systematic Review and Meta-analysis.

BACKGROUND: Ultrasound elastography noninvasively estimates tissue hardness. Studies have evaluated elastography for differentiating malignant from benign lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration. Several methods of performing elastography are described with variable diagnostic accuracy. METHODS: The aim of this study was to evaluate endobronchial ultrasound-guided elastography in differentiating malignant from benign mediastinal lymphadenopathy. We performed a systematic search of the PubMed and Embase databases to extract the relevant studies. A diagnostic accuracy meta-analysis was carried out to calculate the pooled sensitivity and specificity [with 95% confidence intervals (CIs)], and positive and negative likelihood ratios of elastography. RESULTS: After a systematic search, 20 studies (1600 patients, 2712 nodes) were selected. The pooled sensitivity and specificity of elastography were 0.90 (95% CI, 0.84-0.94) and 0.79 (95% CI, 0.73-0.84), respectively. The summary receiver operating curve demonstrated an area under the curve for elastography of 0.90 (0.88-0.93). The positive and negative likelihood ratios and the diagnostic odds ratio were 4.3 (95% CI, 3.3-5.5), 0.12 (95% CI, 0.07-0.20), and 35 (95% CI, 19-63), respectively. Of the most commonly described methods, the color classification method (type 3 malignant vs. type 1 benign) demonstrated the highest area under the curve of 0.91 (0.88-0.93). There was significant heterogeneity and publication bias. Subgroup analyses indicated no significant difference between the sensitivity and specificity of quantitative and qualitative elastography methods. CONCLUSIONS: Ultrasound elastography is useful in differentiating malignant and benign lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration. However, elastography does not replace the requirement of lymph node aspiration.

Head and Neck Surgery During COVID-19 Pandemic: Experience from a Tertiary Care in India.

Head and neck pathologies requiring surgical intervention are considered a high-risk subsite in the context of COVID-19 pandemic by virtue of its close proximity to the mucosa of the upper aerodigestive tract. Retrospective review of all head and neck surgical procedures is undertaken during the pandemic from 23rd April 2020 to 30th September 2020. One hundred procedures were performed on 98 patients. COVID-19 status determined by SARS-Cov-2 RT-PCR at baseline was negative for 81, positive in 8 and unknown in 11. The RT-PCR negative subgroup included 40 diagnostic procedures and 41 ablative and or reconstructive procedures for head and neck neoplasms. None of the patients or health-care workers converted to COVID-19-positive status during the duration of the hospital stay. There were no cases with 30-day mortality. Clavien-Dindo grading for postoperative complications was as follows: 1-4, 2-12, 3a-2, 3b-1. Eleven patients with unknown COVID-19 status at baseline underwent emergency tracheostomy in a COVID-19 designated operating room for upper airway obstruction secondary to head and neck cancer. Of the 8 procedures conducted on known cases of COVID-19, 6 were tracheostomies performed for COVID-19 ARDS. The rest were maxillectomy for acute invasive mucormycosis and incision and drainage for parotid abscess. A matched-pair analysis was performed with similarly staged historical cohort operated during January to December 2016 to compare peri-operative complication rates (Clavien-Dindo Score). Incidence of complication with higher Clavien Dindo Score (>/=3a) was found to be lower in those patients operated during the pandemic (p=0.007). By meticulous preoperative COVID-19 screening and isolation, head and neck surgical procedures can be continued to avoid delay in diagnosis and treatment without jeopardising the risk of transmission of COVID-19 to the patients or health-care workers.

Otolaryngologic Manifestation and Long-Term Outcome in Mild COVID-19: Experience from a Tertiary Care Centre in India.

This study endeavours to comprehensively the study the spectrum of ENT manifestations in mild and asymptomatic COVID-19 and observe the natural course of anosmia and dysgeusia consequent to SARS-Cov-2 infection. A prospective cohort study was undertaken at a tertiary care centre in India on admitted patients with RT-PCR proven COVID-19. Patients were included provided the baseline National Early Warning Score (NEWS) was less than 4. Patients were screened for ENT manifestations using a questionnaire at baseline, 7 days, 14 days and 28 days. 225 patients were included in the study. Of these complete data at 4 weeks was available for 210. Out of 145 patients with mild COVID-19 (asymptomatic = 80), ENT manifestations accounted for 66.2% of all symptoms. Smell and taste disturbance had an overall incidence of 20% and 45% of ENT manifestations. Temporal trends of the recovery rate of anosmia and dysgeusia were 53.6% and 66.7% at 2 weeks, respectively. Corresponding rates at 3 weeks were 89.29% and 86.7%, respectively. By the end of 4 weeks 96% of the patients had recovered completely. The incidence of anosmia and dysgeusia in this study parallels the rates reported from other Asian countries, albeit, lower than the rates quoted from the Western Hemisphere. We recommend structured reporting of all ENT manifestations especially smell and taste disturbances to accurately identify individuals infected with SARS-Cov-2.

EBUS-TBNA versus EUS-B-FNA for the evaluation of undiagnosed mediastinal lymphadenopathy: The TEAM randomized controlled trial.

BACKGROUND: Endobronchial Ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a standard of care modality for the evaluation of mediastinal lymphadenopathy. Transesophageal Bronchoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-B-FNA), wherein one introduces the EBUS bronchoscope through the esophageal route, is also a safe and efficacious diagnostic modality for sampling the mediastinal lymph nodes. The objective of this study was to compare the diagnostic yield and patient comfort with these two available approaches. METHODS: We randomized subjects with predominant subcarinal or lower left paratracheal mediastinal lymph node enlargement to either EBUS-TBNA or EUS-B-FNA (50 to each group). Co-Primary objectives were the comparison of adequate and diagnostic aspirates between groups. Key secondary objectives were a comparison of Operator rated cough and Operator rated procedural comfort on Visual Analog scale (VAS), procedure duration and complications between the groups. RESULTS: Baseline characteristics were comparable between the groups. The proportion of adequate (EBUS-TBNA 46/50; 92% and EUS-B-FNA 48/50;96%, P = 0.4) and diagnostic aspirates (EBUS-TBNA 38/50; 76% and EUS-B-FNA 36/50;74%, P = 0.4) were similar between the two groups. Operator rated cough was significantly less, and Operator rated patient comfort significantly higher with the EUS-B-FNA approach. Procedure duration was significantly shorter with EUS-B-FNA [18.1(14.4) minutes versus 16.4 (49.6) minutes, P < 0.001]. Minor complications occurred in one patient in the EBUS-TBNA group and none in the EUS-B-FNA group. CONCLUSION: During the endosonographic evaluation for undiagnosed mediastinal lymphadenopathy located at predominantly the subcarinal or lower left paratracheal stations, EUS-B-FNA as compared with EBUS-TBNA provides greater patient comfort with a similar diagnostic yield.

Rigid Mini-Thoracoscopy Versus Semirigid Thoracoscopy in Undiagnosed Exudative Pleural Effusion: The MINT Randomized Controlled Trial.

BACKGROUND: There is debate regarding the ideal instrument for medical thoracoscopy. The authors compared rigid mini-thoracoscopy with semirigid thoracoscopy for thoracoscopic pleural biopsy. METHODS: Consecutive subjects with undiagnosed exudative pleural effusion were randomized (1:1 ratio) to mini-thoracoscopy or semirigid thoracoscopy groups. The primary objective was a comparison of the diagnostic yield of pleural biopsy. Key secondary outcomes were the comparison of sedative/analgesic dose, operator-rated and patient-rated pain on visual analog scale (VAS), operator-rated overall procedural satisfaction (VAS), pleural biopsy size, and complications between the groups. RESULTS: Of the 88 screened subjects, 73 were randomized: 36 to mini-thoracoscopy and 37 to semirigid thoracoscopy. Diagnostic yield of pleural biopsy in the mini-thoracoscopy (69.4%) and semirigid thoracoscopy groups (81.1%) was similar on intention-to-treat analysis (P=0.25). Although the operator-rated overall procedure satisfaction scores were similar between groups (P=0.87), operator-rated pain [VAS (mean±SD), 43.5±16.7 vs. 31.7±15.8; P<0.001] and patient-rated pain (VAS, 41.9±17.3 vs. 32.1±16.5; P=0.02) scores were greater in the mini-thoracoscopy group. Mean dose of fentanyl and midazolam received was similar between the 2 groups (P=0.28 and 0.68, respectively). Biopsy size was larger in the mini-thoracoscopy group (16.1±4.5 vs. 8.3±2.9 mm; P<0.001). Three minor complications occurred in the mini-thoracoscopy group and 6 in the semirigid thoracoscopy group (P=0.11). There were no serious adverse events or procedure-related mortality. CONCLUSION: Diagnostic yield of rigid mini-thoracoscopy is not superior to semirigid thoracoscopy. Use of semirigid thoracoscope may provide greater patient comfort.

Tracheobronchial puncture-site nodular reaction (TPNR) following endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): Systematic review of case reports.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive and efficacious diagnostic modality for lung cancer staging and evaluation of undiagnosed mediastinal lymphadenopathy. Procedure-related complications are uncommon. We herein report an infrequently described phenomenon following EBUS-TBNA in which two patients developed nodular granulation tissue at the tracheobronchial puncture site. On systematic review, we found description of such phenomena by terminologies such as endobronchial inflammatory polyp, granuloma, and endobronchial mass. The endobronchial inflammatory polyp has been one of the most commonly used terminologies for these; but in most cases, the classical features of an inflammatory polyp are lacking. We propose the term, tracheobronchial puncture-site nodular reaction (TPNR) with further classification into granulomatous and nongranulomatous subtypes, for standardized reporting of such reactions following transbronchial needle aspiration procedures. Knowledge of this entity and standardized nomenclature shall help in better characterization of the outcomes and risk factors for the occurrence of these reactions.

A young man with hemoptysis: Rare association of idiopathic pulmonary hemosiderosis, celiac disease and dilated cardiomyopathy.

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of recurrent diffuse alveolar hemorrhage (DAH) with no specific treatment. Herein, we discuss a case of hemoptysis, who had IPH and other rare associations. A 19-year-old man presented with recurrent hemoptysis, generalized weakness and progressive dyspnea for 3 years. Earlier, he was diagnosed with anemia and was treated with blood transfusions and hematinics. On examination he had pallor, tachycardia and was underweight. Investigations revealed low level of hemoglobin (7.8 g/dl) and iron deficiency. An electrocardiography (ECG) showed sinus tachycardia, interventricular conduction delay and T-wave inversion. Echocardiography revealed dilated cardiomyopathy with left ventricular dysfunction. Computed tomography of the chest demonstrated bilateral diffuse ground glass opacity suggestive of pulmonary hemorrhage. Pulmonary function tests showed restrictive pattern with increased carbon monoxide diffusion. Bronchoalveolar lavage and transbronchial lung biopsy showed hemosiderin-laden macrophages. Patient could recall recurrent episodes of diarrhea in childhood. Serum antitissue transglutamase antibodies were raised (291.66 IU/ml, normal <30 IU/ml). Duodenal biopsy showed subtotal villous atrophy consistent with celiac disease. He was started on gluten-free diet, beta blockers and diuretics. After two years of treatment, he has been showing consistent improvement. Screening for CD is important in patients with IPH. Cardiomyopathy forms rare third association. All three show improvement with gluten-free diet.

Pleuro-peritoneal lymphomatosis with concurrent tonsillar involvement in T-cell nonHodgkin's lymphoma: Clinical presentation mimicking disseminated tuberculosis.

A young male patient had been evaluated for pleural effusion at another center wherein on the basis of exudative, lymphocyte predominant pleural effusion with high pleural fluid adenosine deaminase (ADA) levels and tuberculin skin test (TST) reactivity, antituberculous medications had been administered. Reevaluation in view of worsening symptoms led to confirmation of the diagnosis of T-cell lymphoblastic lymphoma with pleuro-peritoneal lymphomatosis and tonsillar involvement. This case highlights the fact that elevated ADA levels should not be taken as surrogate for a diagnosis of TB in the absence of histopathological/microbiological confirmation even in countries with high tuberculosis (TB) prevalence. Tonsil in an uncommon site of involvement in patients with T-cell lymphoma. As the diagnosis in our patient was confirmed from biopsy of a tonsillar mass, a thorough physical examination should be performed in all patients with a suspected diagnosis of lymphoma.

Dermatological manifestations in HIV-infected patients at a tertiary care hospital in a tribal (Bastar) region of Chhattisgarh, India.

BACKGROUND: Cutaneous disorders during HIV infection are numerous and skin is often the first and only organ affected during most of the course of HIV disease. Some Cutaneous disorders reflect the progression of HIV disease; though the relation is still controversial. AIMS: The objective of this study, conducted at a tertiary care centre in Bastar, Jagdalpur, is to estimate the status of cutaneous manifestation in HIV-infected patients and its relationship with CD4 cell counts. METHODS: We enrolled 137 HIV positive subjects. Demographic information such as age, gender, weight, height, socioeconomic status, and educational status were recorded. Laboratory parameter (CD4 counts) and treatment regimen were noted. Patients were examined for skin disorders by a dermatologist. Data were analyzed using chi-square test for categorical variables. RESULTS: Majority of the patients were from rural area (65.69%) and belonged to a low socioeconomic and educational status. 30.65% of the patients were housewives, 23.35% drivers, and 16.78% labourers. Predominant mode of transmission was heterosexual contact (94.16%). Most common HIV-related dermatological manifestations were seborrheic dermatitis (74.16%), xerosis (52.5%), generalized skin hyperpigmentation 56 (46.67%), onychomycosis 53 (44.16%), pruritic papular eruption 27 (22.5%), oral candidiasis 21 (17.5%), photo dermatitis 21 (17.5%), and scabies 4 (3.33%). Significant correlation with low CD4+ cell counts was found for oral candidiasis (P < 0.0001) and Kaposi's sarcoma (P = 0.03), while other disorders such as seborrheic dermatitis (P = 0.22), xerosis (P = 0.25), and onychomycosis (P = 0.08) were not statistically significant. CONCLUSION: This study showed high prevalence of dermatological manifestations in HIV-infected subjects, and they occur more frequently with progression of HIV and decline in immune functions. Therefore, early diagnosis and management of skin disorders can improve the quality of life of HIV-infected subjects.