Treatment regimens and survival among patients with head and neck squamous cell carcinoma from Mizo tribal population in northeast India - a single centre, retrospective cohort study.

Background: Patients with early-stage head and neck squamous cell carcinoma (HNSCC) are treated using a single-modality approach that involves either surgery (S) or radiotherapy (RT). Conversely, those with advanced-stage disease are treated using a multi-modality approach incorporating a combination of chemotherapy (CT), RT and S. In addition to behavioural factors, such as alcohol and tobacco use, clinical parameters, such as leukocyte and neutrophil counts and T and N classification, have been linked to the survival of patients with head and neck cancer. This retrospective study was designed to provide insights into the types of treatment (induction chemotherapy [IC], concurrent chemoradiotherapy [CCRT], S and RT) administered to patients with HNSCC in Mizoram, analyse their 2-year outcome, and identify potential factors that may affect the response to treatment. Methods: A retrospective cohort study was conducted using patients diagnosed with HNSCC between 2017 and 2020 in Mizoram, northeast India. Data on clinical and demographic factors and treatments provided were collected from medical records from the Mizoram State Cancer Institute, Mizoram. Overall survival (OS) and progression free survival (PFS) were determined for each factor using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was used to identify the factors that affected OS and PFS. Multicollinearity test was performed between the predictors using a variance inflation factor cut-off point of 2. Findings: A retrospective study was performed on 210 patients with HNSCC who were followed up for a period of 2 years. The findings revealed that hypopharynx was the most affected site, followed by the nasopharynx, oral cavity, oropharynx, and larynx. Regarding treatment regimens, 85/210 (40.5%) of the patients received IC along with CCRT or RT in a sequential manner. Moreover, 86/210 (41.0%) underwent CCRT alone, 22/210 (10.5%) received RT alone and 17/210 (8.1%) underwent surgery followed by adjuvant CCRT or RT. Two-year OS and PFS estimated using the Kaplan-Meier analysis were 78.1% (95% CI = 72.4%-84.2%) and 57.4% (95% CI = 50.8%-64.8%), respectively. Log-rank test showed that leucocytosis (p = 0.015) and neutrophilia (p = 0.014) exerted effects on OS, whereas nodal involvement (p = 0.005), neutrophilia (p = 0.043) and IC (p = 0.010) exerted effects on PFS. Multivariate analysis indicated that leucocytosis (p = 0.010 [OS], 0.025 [PFS]), neutrophilia (p = 0.029, 0.033), cancer site (laryngeal) (p = 0.009, 0.028) and nodal involvement (N2) (p = 0.020, 0.001) were predictors of poor OS and PFS. Interpretation: OS was better than PFS in HNSCC patients from Mizo population. Multi-modality approach offered survival advantages over single-modality approach. Leucocytosis, neutrophilia, nodal involvement, and cancer sites were associated with poor OS and PFS. More comprehensive research with a larger sample size is needed to confirm the findings from this study. Funding: There is no funding for this study.

Clinical profile of COVID-19 infection among persons with spinal cord injury: a case series.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To report the clinical features and outcomes of spinal cord injury (SCI) patients with COVID-19 and to see if they are any different from COVID-19 in the general population. SETTING: A tertiary care hospital in North-East India. METHODS: Data of already diagnosed traumatic SCI patients with COVID-19 infection reporting to the COVID-19 management team (from June 2021 to November 2021) were collected. The source of data was hospital records (admitted patients) and home visits and teleconsultation logs (home isolation patients). RESULTS: There were eight traumatic SCI patients (five admitted, three in home isolation) with COVID-19 infection. Four patients had complete injury with American Spinal Injury Association Impairment Scale (AIS) Grade A, two with AIS Grade C, and one each of Grade B and D respectively. Five patients were cervical level injuries, and others were T10 level and below. Six patients were categorized as mild clinical illness and one each as moderate and severe illness. Cough was the most common symptom which was seen in seven patients. Only two patients needed oxygen therapy. All eight traumatic SCI patients recovered eventually from COVID-19 symptoms and regained their pre-COVID-19 functional status, 1 month after being free from COVID-19 symptoms. CONCLUSION: The COVID-19 infection did not result in a worsening of functional ability among SCI people after 1-month post-recovery. It also did not affect the SCI patients in doing activities such as rehabilitation exercises at 6 months follow up.

Fermented pork fat (Sa-um) and lifestyle risk factors as potential indicators for type 2 diabetes among the Mizo population, Northeast India.

Over the last few decades, Mizoram has shown an increase in cases of type 2 diabetes mellitus; however, no in-depth scientific records are available to understand the occurrence of the disease. In this study, 500 patients and 500 healthy controls were recruited to understand the possible influence of their dietary and lifestyle habits in relation with type 2 diabetes mellitus. A multivariate analysis using Cox regression was carried out to find the influence of dietary and lifestyle factors, and an unpaired t test was performed to find the difference in the levels of biochemical tests. Out of 500 diabetic patients, 261 (52.3%) were males and 239 (47.7%) were females, and among the control group, 238 (47.7%) were males and 262 (52.3%) were females. Fermented pork fat, Sa-um (odds ratio (OR) 18.98), was observed to be a potential risk factor along with tuibur (OR 0.1243) for both males and females. Creatinine level was found to be differentially regulated between the male and female diabetic patients. This is the first report of fermented pork fat and tobacco (in a water form) to be the risk factors for diabetes. The unique traditional foods like Sa-um and local lifestyle habits like tuibur of the Mizo population may trigger the risk for the prevalence of the disease, and this may serve as a model to study other populations with similar traditional practices.

Whole exome sequencing identifies the novel putative gene variants related with type 2 diabetes in Mizo population, northeast India.

The contribution of genes towards T2D development varies among different population groups across the world. It has been reported that a number of loci involved in T2D susceptibility are common across certain population groups, but ethnicity specific variants are also observed. The population of Mizoram has an independent ethnic identity and there are no scientific records about the history of the Mizo people; which makes this ethnic group unique and interesting to study. The aim of the study focuses on the identification of the gene variants which may contribute to T2D susceptibility in Mizo-Mongloid ethnic tribe of North east India through whole exome sequencing. The variants like 328G > C (KRT18), 997G > T (CYP4A11), 2368 T > C (SLC4A3), 508G > A (SLC26A5), 1659C > T (KCNS1), 650C > A (ABCD1) 821A > T (YTHDC2), 931G > T (PINX1), 3280C > A (TNRC6A), 48C > A(TACO1), 6035A > T(LAMA1), 805C > A(ACP7) and 806A > G(ACP7) variants were not reported for any disease in the database and were found to be pathogenic in different insilico analysis softwares. The changes in protein stability upon mutation has been predicted where 35.71% increases the stability of the protein, while 64.28% of the variants decrease the stability of the protein. These findings present the population specific variants which might involve in the susceptibility to T2D in Mizo population. Further, in this study some gene variants have contribution as a possible diagnostic or prognostic marker for other diseases as well, which suggests the need for performing association analysis for different disease manifestations in Mizo population in the near future.

Genomic profiling of mitochondrial DNA reveals novel complex gene mutations in familial type 2 diabetes mellitus individuals from Mizo ethnic population, Northeast India.

The variants reported for mitochondrial DNA (mtDNA) and type 2 diabetes (T2D) may not be accountable for the disease in certain other populations and the risk depends upon numerous factors which may include genetics, environment as well as ethnicity. This leads to a challenge in identifying, exploring and comparing the variants between diabetic cases and healthy controls in a remote unexplored tribal population. To study the possible contribution of mtDNA variants, we sequenced the entire mitochondrial genomes and the frequencies of mtSNPs, their association with familial T2D and the potential impact of non-synonymous substitutions on protein functions were determined. The mtSNP 8584 G > A (ATP6: A20T) was detected in 14.28% of the diabetic patients and none in the control groups. The mitochondrial ND3 variant 10398A > G was found to be significantly associated with the risk of T2D (OR = 9.489, 95% CI = 1.161-77.54, P value = 0.036). A novel Frame-shift substitution ND5: 81_81ins A at position 12,417 was observed in 53.57% of diabetic individuals. Majority of the variants lie in tRNA-Phe in the non-protein coding region of mtDNA for both diabetic cases and common cases. We concluded that mutations in the coding (synonymous or non-synonymous) and noncoding regions of the mitochondria might have contribution towards the development of T2D. Our study is the first to report the distinct mitochondrial variants which may be attributed to the susceptibility as well as development of type 2 diabetes in an ethnic tribe from northeast India.