Genomic revolution: Transforming tuberculosis diagnosis and treatment with the use of Whole Genome Sequencing - A consensus statement.

Tuberculosis (TB) is a preventable, treatable, and curable disease. However, in 2020, 9∙9 million people were estimated to have developed tuberculosis, and 1.5 million people were estimated to have died from it. Whereas in India, 2.6 million were diagnosed with TB and 436,000 succumbed to TB in 2019. India (26%) is the major contributor to the global drop in TB cases. The COVID-19 pandemic has substantially reduced access to services for the diagnosis and treatment of TB, resulting in an increase in deaths and a reversal in global progress. [1] Presently, TB incidence is falling at a rate of 2% per year, obstructed mainly by the rearing pandemic of drug-resistant tuberculosis (DRTB). Particularly concerning is multi-drug resistant TB (MDRTB), defined as resistance towards isoniazid (INH) and rifampicin (RIF). [2] The World Health Organization (WHO) targeted to reduce worldwide TB incidence by 90% until 2035. (1) Early initiation of effective treatment based on susceptibility patterns of the Mycobacterium tuberculosis complex (MTBC) is considered key to successful TB control in countries with high DRTB incidence. Worldwide MDRTB treatment outcomes are poor, with cure rates less than 60% (2) due to the lack of comprehensive Drug Susceptibility Testing (DST) in most high MDRTB burden countries. This is leading to the inadequate anti-TB activity of the provided regimens (3-5), unlike regimens advised for DST assure optimal results. (6) In addition to resistances to the established regimens, the resistance to the newer DRTB drugs is increasing. On World TB Day 2022, Academy of Advanced Medical Education, Thyrocare Technologies Limited and HyastackAnalytics - IITB along with expert pulmonologist and renowned physicians from India convened for an advisory board meeting in Delhi on 20th March 2022 to discuss the role of Whole Genome Sequencing (WGS) in the diagnosis and management of TB. Objectives and specific topics relating to WGS in MDRTB were discussed, each expert shared their views, which led to a group discussion with a commitment to putting the patient first, and increasing their collective efforts, the organizations recognized that it is possible to make this goal a reality. The organizations involved in the discussion have declared their commitment to engaging in collaborative efforts to tackle DRTB detection efficiently. They advocate for strengthening access to WGS TB services, controlling and preventing TB, improving surveillance and drug resistance management, and investing in research and development. This Round Table serves as a framework to build on and ensure that the goal of ending TB is achievable with WGS services wherever needed. Post discussion, a uniform consensus was said to be arrived if more than 80% board members agreed to the statement. The present paper is the outcome of aspects presented and discussed in the advisory board meeting.

Prevalance of tuberculosis amongst healthcare workers, working in DOTS/sputum microscopy centre in two different districts of state of Uttarakhand & Uttar Pradesh of India.

BACKGROUND & OBJECTIVE: The Healthcare workers (HCWs) who work in DOTS/Sputum microscopy centre are exposed to higher risk of contacting tuberculosis (TB) comparatively to other health workers who are serving the other health sectors. The HCWs in DOTS are more exposed due to direct contact with patients suffering from TB or through sharing the infected air space with the infectious patients. The aim of the study is to know the prevalance of TB disease amongst the HCWs who are working in DOTS cum Sputum Microscopy Centre's under RNTCP in two different districts of state of Uttar Pradesh (UP) and Uttarakhand (UK) of india. METHODS: The prospective cross-sectional study is conducted in two districts of different states having high burden of TB disease in UP and low burden of TB disease in UK state. All 100% (130) staff i.e. Medical officers, Sputum microscopy technicians, DOTS providers of DOTS cum Sputum Microscopy centre's of both selected Ghaziabad (UP) and Dehradun (UK) districts are covered in the study. RESULTS: The 4.6% (6) healthcare workers of both the districts were taking ATT at the time of interview and 13.8% (18) HCWs had taken the ATT in past. The 62.5% (15) HCWs i.e 55.5% (5) from Dehradun district and 66.6% (10) from Ghaziabad district preferred to have a ATT from the private medical store inspite of taking DOTS with assumption of low efficacy of drugs and high toxicity. The 58.33% (14) HCWs ie 55.5% (5) staff members of DOTS/sputum microscopy centre in Dehradun & 60.0% (9) staff members of DOTS/sputum microscopy centre in Ghaziabad district had not notified about the status of their disease to the health care authority due the assumption that they may be asked to leave the job or to go on a long unpaid leave. CONCLUSION: The 18.4% (24) HCWs of both the district got TB disease during their working in DOTS/Sputum microscopy centre and 4.6% (6) HCWs of both the districts were taking the ATT at the time of interview.

Kiloh-Nevin syndrome: an unusual cause of forearm pain.

The popularity of weight training, bodybuilding and general physical conditioning has led to an increased rate of musculoskeletal injuries, such as nerve compression caused by muscle hypertrophy and, stretching of nerves peripherally. We present a case of anterior interosseous nerve (AIN) entrapment syndrome/neuropathy otherwise known as Kiloh-Nevin syndrome in a 22-year-old weightlifter. Knowledge of this injury is paramount for practitioners to increase awareness among athletes and bodybuilders.

Prevalence of onychomycosis in patients with diabetes mellitus: A cross-sectional study from a tertiary care hospital in North India.

Background Though diabetes mellitus (DM) is a well-recognised risk factor for onychomycosis (OM), the epidemiology of OM in diabetic patients remains largely unexplored, especially from the Indian subcontinent. Aims and objectives To estimate the prevalence of OM in diabetic patients, to identify and analyse risk factors, and correlate the severity of nail changes with glycemic control (HBA1c). Methods This cross-sectional, analytical study involved 300 diabetic patients. Patients with the clinical diagnosis of OM, supplanted by at least two of the four tests (KOH, culture, onychoscopy and nail histopathology) were considered cases of OM. Demographic and haematological profile was analysed using chi-square test/ Fischer's exact test. Logistic regression was applied to assess the independent risk factors. Results The prevalence of OM in DM patients was 34% (102/300) and significant risk factors included; age >60 years, male gender, closed shoes, disease duration >5 years, high BMI (>25) and lack of awareness about nail changes. Distal and lateral subungual OM (78%) was the commonest presentation followed by proximal subungual OM, superficial OM and total dystrophic OM. Correlation between HbA1c and the number of nails involved was found to be significant. Limitation As cases were recruited from a hospital setting, there could be chances of Berksonian bias. Conclusion The prevalence of OM in diabetic patients is high and the severity of nail changes correlates with HbA1C levels. It is important to diagnose OM early in order to treat and prevent complications.

Prognostic significance of soft tissue deposits in head and neck squamous cell carcinoma: a systematic review and meta-analysis.

Soft tissue deposits, also known as tumour deposits (TDs), have not been studied well in head and neck squamous cell carcinoma (HNSCC) and are not included in any of the staging systems or treatment guidelines. The aim of this systematic review was to determine the prevalence and prognostic implications of TDs in patients with HNSCC. This systematic review of the literature was conducted following the PRISMA guidelines. The PubMed, Embase, and Scopus electronic databases were searched for relevant studies, from inception to August 2022. Although 14 studies qualified for inclusion, only eight were finally included in the review due to the considerable overlap of patients in several studies. Data from 7127 patients were analysed. The pooled prevalence of TDs was 21% (95% confidence interval (CI) 9-33%). The presence of TDs was adversely associated with overall survival and disease-free survival, with hazard ratios of 2.08 (95% CI 1.60-2.70) and 2.56 (95% CI 1.97-3.32), respectively. TDs are detected in a significant number of patients with HNSCC and adversely affect survival. Longitudinal prospective studies are needed to evaluate the prognostic implications of TDs in HNSCC for their potential role in cancer staging and adjuvant treatment planning.

Drug resistant tuberculosis among elderly: Challenges.

The article deals with challenges faced by the geriatric populations while on MDR treatment. Risk factors like tobacco use, low socio-economic status, previous disease, longer delays in seeking treatment and reduced mobility are some of the challenges while initiating MDR treatment. Other issues like drug-related adverse events and increased co-morbidity pose a major challenge while treating patients. Susceptibility among the geriatric age group includes various anatomical and physiological changes including nutritional deficiencies and co morbidities.

Utilization of health care services by elderly for respiratory diseases including TB - Challenges.

Progressive functional decline of all body organ systems in association with decreased immunity makes elderly vulnerable to all types of diseases including respiratory diseases. Advances in medical fields have resulted in increasing proportion of elderly globally. Healthcare demands of elderly population are complex. Provision of healthcare services for this continuously increasing population subgroup & ensuring their adequate utilization is full of challenges. These are demographic, socioeconomic, financial, physical accessibility, quality of healthcare services, attitudinal & transportation related. Large size of this subgroup with special healthcare needs in context of limited available resources of middle income country like India is the biggest challenge. Poor educational status & socioeconomic condition of Indian elderly, dependence on family, absence of formal social security & healthcare security complicates situation further. Condition of elderly females is particularly worse. In view of poor physical ability with often associated physical disability makes accessibility of healthcare services also significant factor. Overcoming negative attitudinal factors prevalent in Indian elderly & make them utilize available healthcare services is another huge challenge. Quality of healthcare services in form of availability of required expertise & equipments, attitude of healthcare providers towards elderly patients & convenience in utilization of these services also play an important role. Special provisions in TB control program for elderly in view of their complex needs, high prevalence, morbidity & mortality are also required.

Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

Nociceptor Neurons Magnify Host Responses to Aggravate Periodontitis.

Periodontitis is a highly prevalent chronic inflammatory disease that progressively destroys the structures supporting teeth, leading to tooth loss. Periodontal tissue is innervated by abundant pain-sensing primary afferents expressing neuropeptides and transient receptor potential vanilloid 1 (TRPV1). However, the roles of nociceptive nerves in periodontitis and bone destruction are controversial. The placement of ligature around the maxillary second molar or the oral inoculation of pathogenic bacteria induced alveolar bone destruction in mice. Chemical ablation of nociceptive neurons in the trigeminal ganglia achieved by intraganglionic injection of resiniferatoxin decreased bone loss in mouse models of experimental periodontitis. Consistently, ablation of nociceptive neurons decreased the number of osteoclasts in alveolar bone under periodontitis. The roles of nociceptors were also determined by the functional inhibition of TRPV1-expressing trigeminal afferents using an inhibitory designer receptor exclusively activated by designer drugs (DREADD) receptor. Noninvasive chemogenetic functional silencing of TRPV1-expressing trigeminal afferents not only decreased induction but also reduced the progression of bone loss in periodontitis. The infiltration of leukocytes and neutrophils to the periodontium increased at the site of ligature, which was accompanied by increased amount of proinflammatory cytokines, such as receptor activator of nuclear factor κΒ ligand, tumor necrosis factor, and interleukin 1ß. The extents of increase in immune cell infiltration and cytokines were significantly lower in mice with nociceptor ablation. In contrast, the ablation of nociceptors did not alter the periodontal microbiome under the conditions of control and periodontitis. Altogether, these results indicate that TRPV1-expressing afferents increase bone destruction in periodontitis by promoting hyperactive host responses in the periodontium. We suggest that specific targeting of neuroimmune and neuroskeletal regulation can offer promising therapeutic targets for periodontitis supplementing conventional treatments.

Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study.

AIM: To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS: After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION: cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.

Impact of coronavirus disease 2019 on ENT clinical practice and training: the resident's perspective.

BACKGROUND: The arrival of the coronavirus disease 2019 pandemic disrupted life suddenly and forcefully, and healthcare systems around the world are still struggling to come to terms with it. This paper reviews the impact of the pandemic on ENT practice and training. METHODS: The present manuscript was developed as a narrative review to examine the role of otorhinolaryngologists in the management of the pandemic, and assess its impact on practice and training in the specialty. RESULTS: Otorhinolaryngologists handle secretions of organs implicated in disease transmission, leaving them particularly vulnerable even while performing simple procedures. Although the pandemic increased skill expectations, it simultaneously reduced learning opportunities for trainees. In addition, attention to emergencies has been delayed. Further, the suspension of elective procedures has affected patients with malignancies. CONCLUSION: While planning service resumption, provisions need to be made for protective equipment and training; improving teleconsultation services will help provide sustainable care during further waves.