Study to Evaluate the Pattern of Nodal Distribution in Papillary Thyroid Cancer.

Among the thyroid cancers, papillary thyroid cancer (PTC) is the most common with lymphatic metastasis. It has the propensity to spread to the level II-VI lymph nodes in a predictable manner. We evaluated the pattern of nodal distribution at different levels of neck in papillary thyroid cancer in this Observational Prospective study. Total 41 patients of PTC (Papillary thyroid cancer) were included in the study. 36 out of them were diagnosed as PTC by FNAC and underwent total thyroidectomy and central neck dissection, while 5 patients were histologically confirmed cases of PTC on previous hemithyroidectomy and underwent completion thyroidectomy and central neck dissection .Patients with T3/T4 stage or N1 underwent lateral neck dissection also. Clinicopathological factors such as age, sex, tumor stage, nodal metastasis and extracapsular invasion, were evaluated. Lymph node metastasis was noted in 21 patients (51.2%) and all these patients had central (level VI) lymph node involvement. Among 21 patients, pathological ipsilateral lateral neck metastasis was noted in 6 patients (28.57%) at level II, 10 patients (47.62%) at level III and 8 patients (38.10%) at level IV. Only 5 patients (23.81%) had metastasis at level V. Extracapsular invasion was observed in 10 (24.4%) patients. We concluded that patients with PTC show higher rates of metastasis at central neck (level VI) and are not easily detected on clinical examination or by USG due to low sensitivity but are sensitive and specific for lateral neck nodes in late stages . Thus, ipsilateral selective neck dissection should be considered with total thyroidectomy and central neck dissection in presence of clinically or radiologically evident lateral lymph nodes (preoperatively) and in T3, T4 stage (late stages) tumors.

A Prospective Study on Correlation of MERI (Middle Ear Risk Index) Score with Surgical Outcome of Tympano-mastoid Surgery in Patients of CSOM.

Chronic otits media (COM) is surgically treatable disease which includes complete removal of disease and improving hearing via ossicular reconstruction. Therefore, thorough assessment of the disease, ossicles and various factors causing it plays a major role in surgical outcome prediction. MERI (Middle ear risk index) is one such tool being used worldwide. Our aim was to evaluate the surgical outcome of tympanomastoid surgery using MERI and find out correlation between them as well as categorize cases into their severity score in a developing country. Observational prospective study conducted in a tertiary care center. 200 patients were included. After complete history and examination, they were given MERI scores and prediction of surgical outcome was done. Postoperatively it was compared with the real outcome of the surgery. Out of 200 patients, 71.5% had mild, 15.5% had moderate and 13% had severe MERI scores preoperatively. There was a success rate of 88.5% in graft uptake and the mean score of hearing benefit (A-B gain) among patients was 8.75 ± 8.82 dB postoperatively. MERI may be used as a prognostic indicator for predicting surgical outcome. Based on the MERI score, chances of surgical success and hearing benefit can be explained to the patient with certain limitations.

A Study of Pulmonary Function Tests in Patients with Chronic Rhinosinusitis Following Endoscopic Sinus Surgery.

Chronic inflammatory disorders of the upper airways are extremely prevalent and they have a major impact on public health.To assess the change in pulmonary function tests in patients of chronic rhinosinusitis undergoing functional endoscopic sinus surgery pre operatively and post operatively.To evaluate the difference in mean of FEV1, FEV1%, FVC, FVC%, FEV1/FVC in patients of chronic rhinosinusitis undergoing functional endoscopic sinus surgery.Prospective observational study.From July 2019 to September 2020 in Department of ENT and Head & Neck surgery, SMS Medical College, Jaipur.There was a significant improvement in the mean FEV1, FEV1%, FVC, and FVC% values post-surgically (p < 0.05). In our study, there was also a significant improvement in the FEV1/FVC value at one month postoperatively, reflecting the effect of FESS on relieving the symptomatic lower airway obstruction.Our study concludes that following Functional Endoscopic Sinus Surgery there is significant improvement in pulmonary function tests reflecting the improvement of asymptomatic lower airway disease in cases of chronic rhinosinusitis.

A Prospective Randomized Study to Compare Surgical Outcome Using Wet and Dry Temporalis Fascia Graft in Type I Tympanoplasty.

Temporalis fascia is being used as graft material for tympanic membrane repair for over six decades. Though cartilage with or without perichondrium is also being used for different situations, still temporalis fascia graft is being considered as an ideal graft for tympanoplasty. Earlier the dried temporalis fascia was used as a graft but now freshly taken wet temporalis fascia is increasingly being used as a more 'physiological/ live' graft. The present study was planned to compare the results of use of wet and dry temporalis fascia in chronic otitis media mucosal disease. The prospective study was conducted on 100 patients of chronic suppurative otitis media mucosal disease. Chronic ear survey questionnaire were filled to note the impact on quality of life. Otoscopic, oto-endoscopic and examination under microscope performed. Patients were allocated into two groups alternately. Freshly taken wet temporalis graft was used in group I whereas dry temporalis fascia was used in group II. Hearing evaluation by pure tone audiogram was done preoperatively and at 6th months post-operatively. Pre-operative and post-operative hearings in both the groups were compared. Air bone gap closures after surgery in between both the groups were compared to see for any statistical difference. We found similar graft uptake in both the groups after 6 months of surgery. The air bone gap closure in group I was 10.80 ± 5.74 and group II was 9.28 ± 4.81, there was no significant difference. However senior authors noted that in some of the cases in group I with fresh wet graft placement neo-tympanum formation was noticed early showing good circumferential leash of blood vessels all around signifying early vascularisation.

An Observational Study on Association of Clinical Outcome of Diphtheria Cases with Immunization Status: A Tertiary Care Hospital, Jaipur.

BACKGROUND: Diphtheria is an important vaccine preventable disease with varied outcome from mild to death. It was observed that the outcome also gets affected with status of immunization. The outcome is relatively milder in immunized children. OBJECTIVE: To find out the clinical presentation and outcome of diphtheria cases and its association with the immunization status. METHODS: A descriptive analysis of 64 diphtheria cases admitted from January 2019 to May 2020 at SMS hospital, a tertiary care referral hospital in Jaipur. RESULTS: Half of (51.56%, 33/60) patients were in the age group of 6-10 years. The peak load (48.44%) of diphtheria cases was seen in the monsoon season. Around 60% of the patients were fully immunized and around 10% partially immunized, every third case was un-immunized. The most common complication was neurological in 13 cases (20.31%), followed by cardiac complications in 11 cases (17.19%), and respiratory (7.81%). The proportion of complication was much lower (26.3%) in immunized cases as compare to partially immunized and un immunized. The proportion of myocarditis was significantly higher in un immunized cases (40%) than partially immunized (16.7%) and filly immunized group (5.3%). Similarly, Bronchopneumonia was also significantly higher (20%) in unimmunized. CONCLUSION: Our study depicted that there has been a shift of age above 5 years for diphtheria which suggests the need for the booster dose. Also high chances of complications are seen in unimmunized and partially immunized calling for public awareness regarding complete immunization.

Spectrum of Neurological Outcomes in Diphtheria: A Case Series.

Diphtheria is an acute infectious disease caused by the exotoxin produced by Corynebacterium diphtheriae, a gram positive bacteria. It has propensity to affect mainly cardiac muscle and nervous system. To study the percentage, spectrum of patients with various neurological complications and the pattern of recovery in followed up confirmed cases of diphtheria. Single centre prospective analysis of neurological complications in diphtheria patients from June 2019 to September 2020 at SMS Medical College and hospital,Jaipur. In this study, 60 cases were included. Immunised cases were 60% (36 out of 60 cases) whereas unimmunised constituted the rest 40% (24 out of 60 cases). Neurological complications were observed in 15% of the cases (9 out of 60). Isolated palatal palsy was the most common complication (4 out of 9 cases, 44.44%), succeeded by lower limb LMN palsies (2 out of 9 cases, 22.22%) with unilateral facial nerve palsy, bilateral abductor palsy and paralytic ileus constituting the rest (1 out of 9 cases each, 11.11% each). Onset of complications ranged from 10 to 36 days whereas recovery was complete and without any residual sequelae between 60 to 240 days. Our study concluded that neurological complications form a sizeable portion of post diptheritic complications and carries good prognosis, hence timely diagnosis and differentiation from other neuropathies is a pre requisite for rational management and contact tracing.

"An Observational Study on Association of Clinical Diagnosis of Diphtheria with Smear and Culture Test: A Tertiary Care Hospital, Jaipur".

Diphtheria is an acute infectious upper respiratory tract disease caused by toxigenic strains of Corynebacterium diphtheria and can lead to significant morbidity and mortality in all the age groups. Most of the time diagnosis of diphtheria is clinical. There may be a dirty white patch covering one or both tonsils on examination for which throat swabs are collected for Kleb's-Loeffler's Bacillus (KLB) by direct microscopy and for culture and sensitivity of the organism. To find out the association between clinical diagnosis of diphtheria with smear and culture positivity. 674 cases of Clinical diphtheria were admitted from June 2017 to September 2020 at a tertiary care hospital, Sawai Mansingh Hospital, Jaipur. throat, difficulty in swallowing and swelling in the neck. Out of 674 patients of clinical diphtheria, majority 610 cases (90.5%) were found to have both KLB smear and culture negative. 13 cases (1.9%) were found to have both KLB smear and culture positive. 19 cases (2.8%) were found to have KLB smear positive and culture negative and remaining 32 cases (4.8%) were found to have KLB smear negative and culture positive. Out of 19 patients of KLB smear positive,11 cases (3.5%) were found to have complications. Out of 32 culture positive patients,24 cases (7.7%) were found to have complications. Out of 13 patients of both KLB smear and culture positive,11 cases (3.5%) were found to have complications. Our study concluded that the negative report of KLB smear and culture does not rule out diphtheria and it is evident that percentage of complication is high in patients with either KLB smear or culture or both positive with respect to both being negative. The correlation is found to be significant (p < 0.001).

Efficacy of Sucralfate in Alleviating Post Tonsillectomy Symptoms and Morbidity: A Comparative Randomized Interventional Study.

Pain following tonsillectomy still remains the main concern of topic and it occurs along with sever ear pain and trismus until and unless the exposed and inflamed mucosa gets covered with the regenerated mucosa. To study the efficacy of sucralfate in alleviating postoperative pain and morbidity following tonsillectomy. Subjects included in our study were patients which were fulfilling criteria for tonsillectomy and were admitted under the Department of Otorhinolaryngology, SMS Medical College and Hospital, Jaipur from 1st July 2019 to 31st March 2020. 64 patients were evaluated and were randomly allocated into study and control group based on the administration of topical sucralfate. 64 patients who were admitted for tonsillectomy under the Department of Otorhinolaryngology, SMS Medical College and Hospital, Jaipur from 1st July 2019 to 31st March 2020 were included in study. Patients were evaluated and were randomly allocated into study and control group based on the administration of topical sucralfate. The incidence of throat pain and otalgia showed significant difference among both the group following postoperative day 2 onwards. On postoperative day 2, significant difference in trismus was also found. Effective alleviation of pain not only improves early dietary intake of the patients but also allays fear of apprehensive parents.

Fosfomycin versus Nitrofurantoin for the Treatment of Lower UTI in Outpatients.

Introduction Fosfomycin and nitrofurantoin are increasingly being prescribed in outpatients for the oral treatment of urinary tract infection (UTI). Although ample literature is available on the in vitro sensitivity pattern of fosfomycin and nitrofurantoin in UTI cases, clinical data are scant. Methodology Voided midstream urine, collected from patients ≥ 16 years of age of both genders with suspected sign and symptoms, was plated on cystine lactose electrolyte-deficient agar. Uropathogen was defined as an organism known to be associated with the signs and symptoms of UTI with > 10 5 colony forming units/mL of urine. Antimicrobial susceptibility testing was determined by Kirby-Bauer disc diffusion method. Further, for fosfomycin, agar dilution method was also performed. Results A total of 143 patients, 47 treated with fosfomycin and 96 with nitrofurantoin, were followed for clinical outcome. The most common isolated uropathogen was Escherichia coli . In vitro susceptibility rate of uropathogens against fosfomycin and nitrofurantoin was 99.3% and 81.2%, respectively. Overall, the clinical cure rate with fosfomycin and nitrofurantoin treatment groups was 80.85% and 90.06% respectively (not statistically significant). Conclusion Fosfomycin and nitrofurantoin showed good in vitro activity against uropathogens from lower UTI and can be used for empirical therapy in our area. Multiple confounding factors may have contributed to the discrepancy between in vitro susceptibility and clinical cure, which needs to be studied further.

RNA editing enzyme APOBEC3A promotes pro-inflammatory M1 macrophage polarization.

Pro-inflammatory M1 macrophage polarization is associated with microbicidal and antitumor responses. We recently described APOBEC3A-mediated cytosine-to-uracil (C > U) RNA editing during M1 polarization. However, the functional significance of this editing is unknown. Here we find that APOBEC3A-mediated cellular RNA editing can also be induced by influenza or Maraba virus infections in normal human macrophages, and by interferons in tumor-associated macrophages. Gene knockdown and RNA_Seq analyses show that APOBEC3A mediates C>U RNA editing of 209 exonic/UTR sites in 203 genes during M1 polarization. The highest level of nonsynonymous RNA editing alters a highly-conserved amino acid in THOC5, which encodes a nuclear mRNA export protein implicated in M-CSF-driven macrophage differentiation. Knockdown of APOBEC3A reduces IL6, IL23A and IL12B gene expression, CD86 surface protein expression, and TNF-α, IL-1ß and IL-6 cytokine secretion, and increases glycolysis. These results show a key role of APOBEC3A cytidine deaminase in transcriptomic and functional polarization of M1 macrophages.

Mitochondrial hypoxic stress induces widespread RNA editing by APOBEC3G in natural killer cells.

BACKGROUND: Protein recoding by RNA editing is required for normal health and evolutionary adaptation. However, de novo induction of RNA editing in response to environmental factors is an uncommon phenomenon. While APOBEC3A edits many mRNAs in monocytes and macrophages in response to hypoxia and interferons, the physiological significance of such editing is unclear. RESULTS: Here, we show that the related cytidine deaminase, APOBEC3G, induces site-specific C-to-U RNA editing in natural killer cells, lymphoma cell lines, and, to a lesser extent, CD8-positive T cells upon cellular crowding and hypoxia. In contrast to expectations from its anti-HIV-1 function, the highest expression of APOBEC3G is shown to be in cytotoxic lymphocytes. RNA-seq analysis of natural killer cells subjected to cellular crowding and hypoxia reveals widespread C-to-U mRNA editing that is enriched for genes involved in mRNA translation and ribosome function. APOBEC3G promotes Warburg-like metabolic remodeling in HuT78 T cells under similar conditions. Hypoxia-induced RNA editing by APOBEC3G can be mimicked by the inhibition of mitochondrial respiration and occurs independently of HIF-1α. CONCLUSIONS: APOBEC3G is an endogenous RNA editing enzyme in primary natural killer cells and lymphoma cell lines. This RNA editing is induced by cellular crowding and mitochondrial respiratory inhibition to promote adaptation to hypoxic stress.

RNA Editing in Pathogenesis of Cancer.

Several adenosine or cytidine deaminase enzymes deaminate transcript sequences in a cell type or environment-dependent manner by a programmed process called RNA editing. RNA editing enzymes catalyze A>I or C>U transcript alterations and have the potential to change protein coding sequences. In this brief review, we highlight some recent work that shows aberrant patterns of RNA editing in cancer. Transcriptome sequencing studies reveal increased or decreased global RNA editing levels depending on the tumor type. Altered RNA editing in cancer cells may provide a selective advantage for tumor growth and resistance to apoptosis. RNA editing may promote cancer by dynamically recoding oncogenic genes, regulating oncogenic gene expression by noncoding RNA and miRNA editing, or by transcriptome scale changes in RNA editing levels that may affect innate immune signaling. Although RNA editing markedly increases complexity of the cancer cell transcriptomes, cancer-specific recoding RNA editing events have yet to be discovered. Epitranscriptomic changes by RNA editing in cancer represent a novel mechanism contributing to sequence diversity independently of DNA mutations. Therefore, RNA editing studies should complement genome sequence data to understand the full impact of nucleic acid sequence alterations in cancer. Cancer Res; 77(14); 3733-9. ©2017 AACR.

Mitochondrial complex II regulates a distinct oxygen sensing mechanism in monocytes.

Mutations in mitochondrial complex II (succinate dehydrogenase; SDH) genes predispose to paraganglioma tumors that show constitutive activation of hypoxia responses. We recently showed that SDHB mRNAs in hypoxic monocytes gain a stop codon mutation by APOBEC3A-mediated C-to-U RNA editing. Here, we test the hypothesis that inhibition of complex II facilitates hypoxic gene expression in monocytes using an integrative experimental approach. By RNA sequencing, we show that specific inhibition of complex II by atpenin A5 in normoxic conditions mimics hypoxia and induces hypoxic transcripts as well as APOBEC3A-mediated RNA editing in human monocytes. Myxothiazol, a complex III inhibitor, has similar effects in normoxic monocytes. Atpenin A5 partially inhibits oxygen consumption, and neither hypoxia nor atpenin A5 in normoxia robustly stabilizes hypoxia-inducible factor (HIF)-1α in primary monocytes. Several earlier studies in transformed cell lines suggested that normoxic stabilization of HIF-1α explains the persistent expression of hypoxic genes upon complex II inactivation. On the contrary, we find that atpenin A5 antagonizes the stabilization of HIF-1α and reduces hypoxic gene expression in transformed cell lines. Accordingly, compound germline heterozygosity of mouse Sdhb/Sdhc/Sdhd null alleles blunts chronic hypoxia-induced increases in hemoglobin levels, an adaptive response mainly regulated by HIF-2α. In contrast, atpenin A5 or myxothiazol does not reduce hypoxia-induced gene expression or RNA editing in monocytes. These results reveal a novel role for mitochondrial respiratory inhibition in induction of the hypoxic transcriptome in monocytes and suggest that inhibition of complex II activates a distinct hypoxia signaling pathway in a cell-type specific manner.

Transient overexpression of exogenous APOBEC3A causes C-to-U RNA editing of thousands of genes.

APOBEC3A cytidine deaminase induces site-specific C-to-U RNA editing of hundreds of genes in monocytes exposed to hypoxia and/or interferons and in pro-inflammatory macrophages. To examine the impact of APOBEC3A overexpression, we transiently expressed APOBEC3A in HEK293T cell line and performed RNA sequencing. APOBEC3A overexpression induces C-to-U editing at more than 4,200 sites in transcripts of 3,078 genes resulting in protein recoding of 1,110 genes. We validate recoding RNA editing of genes associated with breast cancer, hematologic neoplasms, amyotrophic lateral sclerosis, Alzheimer disease and primary pulmonary hypertension. These results highlight the fundamental impact of APOBEC3A overexpression on human transcriptome by widespread RNA editing.

APOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages.

The extent, regulation and enzymatic basis of RNA editing by cytidine deamination are incompletely understood. Here we show that transcripts of hundreds of genes undergo site-specific C>U RNA editing in macrophages during M1 polarization and in monocytes in response to hypoxia and interferons. This editing alters the amino acid sequences for scores of proteins, including many that are involved in pathogenesis of viral diseases. APOBEC3A, which is known to deaminate cytidines of single-stranded DNA and to inhibit viruses and retrotransposons, mediates this RNA editing. Amino acid residues of APOBEC3A that are known to be required for its DNA deamination and anti-retrotransposition activities were also found to affect its RNA deamination activity. Our study demonstrates the cellular RNA editing activity of a member of the APOBEC3 family of innate restriction factors and expands the understanding of C>U RNA editing in mammals.