Treatment options for resectable hypopharyngeal squamous cell carcinoma: A systematic review and meta-analysis of randomized controlled trials

BACKGROUND: There is uncertainty in the treatment options for resectable hypopharyngeal squamous cell carcinoma. METHODS: A systematic review of randomised controlled trials (RCTs) was performed. Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, Science Citation Index, and Conference Proceedings databases and trial registries were searched until November 2020 for randomized controlled trials performed on resectable hypopharyngeal squamous cell carcinoma. Two systematic review authors independently identified studies and extracted data. The primary outcomes evaluated were overall survival, disease-free survival, any recurrence, local recurrence, loco-regional recurrence, distal recurrence and laryngectomy-free survival. The secondary outcomes were response rates following neoadjuvant treatment and comparison of treatment-related toxicity. Assessment of risk of bias was performed for the selected studies using Cochrane's tool for assessing risk of bias. The studies were evaluated for the quality of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Risk ratios (RR), rate ratios, and hazard ratios (HR) were calculated along with 95% confidence intervals (95% CI). The Meta-analysis was performed using a random-effects model. RESULTS: Five RCTs met the inclusion criteria for this review. The risk of bias was unclear or high for the trials. Non-organ preservation(n = 140) versus organ preservation (n = 144) (two trials): no statistically significant difference could be identified for any of the primary outcomes. Concurrent chemoradiotherapy (n = 37) versus sequential chemotherapy followed by radiotherapy (n = 34) (one trial): no statistically significant difference was noted between the two treatment arms for overall survival, disease-free survival and loco-regional recurrence. Laryngectomy-free survival was found to be superior in concurrent chemoradiotherapy arm (HR:0.28, 95% CI 0.13, 0.57). Induction chemotherapy followed by concurrent chemoradiotherapy (n = 53) versus induction chemotherapy followed by radiotherapy (n = 60) (one trial): no statistically significant difference was noted between the treatment arms for overall survival, disease-free survival and laryngectomy-free survival. Preoperative radiotherapy (n = 24) versus postoperative radiotherapy (n = 23) (one trial): overall survival was found to be better in the postoperative radiotherapy arm (HR:2.44, 95% CI1.18, 5.03). No statistically significant difference was noted in terms of treatment-related toxicity. CONCLUSIONS: There are considerable uncertainties in the management of resectable hypopharyngeal cancer. TRAIL REGISTRATION: PROSPERO registration: CRD42019155613

Hearing Rehabilitation of Patients with Chronic Otitis Media:A Discussion of Current State of Knowledge and Research Priorities

Although chronic otitis media is a major cause of conductive and mixed hearing loss, auditory rehabilitation is currently not optimal for this patient group. Planning for hearing rehabilitation must accompany strategies for infection control when surgically managing patients with chronic otitis media. Several barriers prevent adequate hearing restoration in such a heterogeneous patient population. A lack of standardized reporting of surgical interventions, hearing, and quality of life outcomes impedes meta-analyses of existing data and the generation of high-quality evidence, including cost-effectiveness data, through prospective studies. This, in turn, prevents the ability of clinicians to stratify patients based on prognostic indicators, which could guide the decision-making pathway. Strategies to improve reporting standards and methods have the potential to classify patients with chronic otitis media preoperatively, which could guide decision-making for hearing restoration with ossiculoplasty versus prosthetic hearing devices. Appropriately selected clinical guidelines would not only foster directed research but could enhance patient-centered and evidence-based decision-making regarding hearing rehabilitation in the surgical planning process

Success rates in restoring hearing loss in patients with chronic otitis media:A systematic review

Abstract Objective To assess the effectiveness of tympanoplasty in treating chronic otitis media‐related hearing loss, published literature was systematically reviewed to determine the clinical success rate of tympanoplasty at restoring hearing in chronic otitis media patients at a minimum follow‐up period of 12‐months. Data Sources PubMed, Embase and the Cochrane Library. Methods Two independent reviewers performed literature searches. Publications reporting long‐term (≥12‐month) hearing outcomes and complications data on adult and pediatric patients with chronic otitis media were included and assessed for risk of bias and strength of evidence. To assess how tympanoplasty influences long‐term hearing outcomes, data on pure tone audiometry (air‐bone gap) and complications were extracted and synthesized. Results Thirty‐nine studies met the inclusion criteria. Data from 3162 patients indicated that 14.0% of patients encountered postoperative complications. In adult patients, mean weighted air‐bone gap data show closure from 26.5 dB hearing level (HL) (preoperatively) to 16.1 dB HL (postoperatively). In studies that presented combined adult and pediatric data, the mean preoperative air‐bone gap of 26.7 dB HL was closed to 15.4 dB HL. In 1370 patients with synthesizable data, 70.7% of patients had a postoperative air‐bone gap ˂ 20 dB HL at long‐term follow‐up. Finally, subgroup analysis identified that mean improvement in ABG closure for patients with and without cholesteatoma was 10.0 dB HL and 12.4 dB HL, respectively. Conclusion In patients with chronic otitis media, tympanoplasty successfully closed the air‐bone gap to within 20 dB HL in 7/10 cases and had an overall complication rate of 14.0%. Level of Evidence 2a

Estimation of Serum Levels of Heavy Metals in Patients with Chronic Invasive Fungal Rhinosinusitis Before the COVID-19 Era: A Pilot Study

Objective:Various metals play role in the survival and pathogenesis of the invasive fungal disease. The objectives of this study were to compare the levels of heavy metals in patients with chronic invasive fungal rhinosinusitis (CIFR) and healthy controls, and to analyze their role in disease outcome.Methods:Twenty-three patients (15 with invasive mucormycosis and 8 with invasive aspergillosis, Group 1), and 14 healthy controls (Group 2) were recruited. Blood samples were collected from each group into ion-free tubes and analyzed for serum levels of Nickel (Ni), Copper (Cu), Zinc (Zn), Gallium (Ga), Arsenic (As), Selenium (Se), Rubidium (Rb), Strontium (Sr), Cadmium (Cd), and Lead (Pb). The final outcome of the patients during their hospital stay was categorized clinico-radiologically as improved or worsened, or death.Results:The levels of all metals were higher in Group 1 except for As and Pb. However, the differences in Cu (p=0.0026), Ga (p=0.002), Cd (p=0.0027), and Pb (p=0.0075) levels were significant. Higher levels of Zn (p=0.009), Se (p=0.020), and Rb (p=0.016) were seen in the invasive aspergillosis subgroup. Although Zn (p=0.035), As (p=0.022), and Sr (p=0.002) levels were higher in patients with improved outcome, subgroup analysis showed no differences.Conclusion:The levels of some heavy metals in CIFR significantly differ from those of the general population and also vary with the type of the disease and its outcome. These levels may not have a direct effect on the outcome of the patient, but they do play a role in the pathogenesis of the invading fungus

Overexpression of Prothymosin Alpha Predicts Poor Disease Outcome in Head and Neck Cancer

In our recent study, tissue proteomic analysis of oral pre-malignant lesions (OPLs) and normal oral mucosa led to the identification of a panel of biomarkers, including prothymosin alpha (PTMA), to distinguish OPLs from histologically normal oral tissues. This study aimed to determine the clinical significance of PTMA overexpression in oral squamous cell hyperplasia, dysplasia and head and neck squamous cell carcinoma (HNSCC).Immunohistochemistry of PTMA protein was performed in HNSCCs (n = 100), squamous cell hyperplasia (n = 116), dysplasia (n = 50) and histologically normal oral tissues (n = 100). Statistical analysis was carried out to determine the association of PTMA overexpression with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients.<0.001). Chi-square analysis showed significant association of nuclear PTMA with advanced tumor stages (III+IV). Kaplan Meier survival analysis indicated reduced disease free survival (DFS) in HNSCC patients (p<0.001; median survival 11 months). Notably, Cox-multivariate analysis revealed nuclear PTMA as an independent predictor of poor prognosis of HNSCC patients (p<0.001, Hazard's ratio, HR = 5.2, 95% CI = 2.3–11.8) in comparison with the histological grade, T-stage, nodal status and tumor stage.Nuclear PTMA may serve as prognostic marker in HNSCC to determine the subset of patients that are likely to show recurrence of the disease

Nuclear S100A7 Is Associated with Poor Prognosis in Head and Neck Cancer

Tissue proteomic analysis of head and neck squamous cell carcinoma (HNSCC) and normal oral mucosa using iTRAQ (isobaric tag for relative and absolute quantitation) labeling and liquid chromatography-mass spectrometry, led to the identification of a panel of biomarkers including S100A7. In the multi-step process of head and neck tumorigenesis, the presence of dysplastic areas in the epithelium is proposed to be associated with a likely progression to cancer; however there are no established biomarkers to predict their potential of malignant transformation. This study aimed to determine the clinical significance of S100A7 overexpression in HNSCC.Immunohistochemical analysis of S100A7 expression in HNSCC (100 cases), oral lesions (166 cases) and 100 histologically normal tissues was carried out and correlated with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients. Overexpression of S100A7 protein was significant in oral lesions (squamous cell hyperplasia/dysplasia) and sustained in HNSCC in comparison with oral normal mucosa (p(trend)<0.001). Significant increase in nuclear S100A7 was observed in HNSCC as compared to dysplastic lesions (p = 0.005) and associated with well differentiated squamous cell carcinoma (p = 0.031). Notably, nuclear accumulation of S100A7 also emerged as an independent predictor of reduced disease free survival (p = 0.006, Hazard ratio (HR = 7.6), 95% CI = 1.3-5.1) in multivariate analysis underscoring its relevance as a poor prognosticator of HNSCC patients.Our study demonstrated nuclear accumulation of S100A7 may serve as predictor of poor prognosis in HNSCC patients. Further, increased nuclear accumulation of S100A7 in HNSCC as compared to dysplastic lesions warrants a large-scale longitudinal study of patients with dysplasia to evaluate its potential as a determinant of increased risk of transformation of oral premalignant lesions

Developing Standard Treatment Workflows—way to universal healthcare in India

Primary healthcare caters to nearly 70% of the population in India and provides treatment for approximately 80–90% of common conditions. To achieve universal health coverage (UHC), the Indian healthcare system is gearing up by initiating several schemes such as National Health Protection Scheme, Ayushman Bharat, Nutrition Supplementation Schemes, and Inderdhanush Schemes. The healthcare delivery system is facing challenges such as irrational use of medicines, over- and under-diagnosis, high out-of-pocket expenditure, lack of targeted attention to preventive and promotive health services, and poor referral mechanisms. Healthcare providers are unable to keep pace with the volume of growing new scientific evidence and rising healthcare costs as the literature is not published at the same pace. In addition, there is a lack of common standard treatment guidelines, workflows, and reference manuals from the Government of India. Indian Council of Medical Research in collaboration with the National Health Authority, Govt. of India, and the WHO India country office has developed Standard Treatment Workflows (STWs) with the objective to be utilized at various levels of healthcare starting from primary to tertiary level care. A systematic approach was adopted to formulate the STWs. An advisory committee was constituted for planning and oversight of the process. Specialty experts' group for each specialty comprised of clinicians working at government and private medical colleges and hospitals. The expert groups prioritized the topics through extensive literature searches and meeting with different stakeholders. Then, the contents of each STW were finalized in the form of single-pager infographics. These STWs were further reviewed by an editorial committee before publication. Presently, 125 STWs pertaining to 23 specialties have been developed. It needs to be ensured that STWs are implemented effectively at all levels and ensure quality healthcare at an affordable cost as part of UHC

Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions