Search

Summary Background The aim of our study was to determine the presence and pattern of ventricular hyperadduction (VH) following unilateral vocal fold (VF) paralysis/paresis and that following unilateral cordectomy (UC). Methods The authors independently reviewed charts and flexible videostroboscopic recordings of 214 patients diagnosed with unilateral VF paralysis/paresis and those who had undergone UC from 2015 to 2018. The presence and pattern of VH was noted. VH was considered to be present when the false vocal fold (FVF) obliterated 50% or more of the true vocal fold width during phonation, with or without FVF vibration. The true vocal fold width was considered to be that which was visible on abduction of the VFs. Categorical variables were presented in numbers and percentages and qualitative variables were correlated using Chi-Square test. Odds ratio with 95% Confidence Interval was calculated. Results In 154 patients diagnosed as unilateral VF paralysis/paresis 85 patients had a VH pattern (55.19%) with contralateral VH observed in 74 (87.05%), ipsilateral VH observed in 6 (7.05%) and bilateral VH observed in five patients (5.88 %). The total number of patients of UC was 60 with 36 of these patients developing a VH (60%). Ipsilateral VH was observed in 28 of these 36 patients (77.77%), three patients developed contralateral VH (8.33%) and five patients developed bilateral VH (13.88%). Conclusion Ipsilateral ventricular hyper-adduction following unilateral cordectomy in the group of patients that develop hyperadduction is a significant finding in our study suggesting possibility of unilateral central phonatory control of the FVF. Contralateral ventricular hyper-adduction following unilateral paralysis and paresis, in the group of patients that develop hyperadduction is a significant finding in our study and this finding resonates with previously published papers. A finding of unilateral VH may serve as a possible indicator of the occasionally challenging diagnosis of vocal fold paresis. Study type : Retrospective, Observational

Background: Anti-cancer agents are known to be toxic, leading to a number of adverse drug reactions (ADRs). ADRs not only increase the financial burden on the patient/healthcare system but also decrease the quality of life. Understanding the burden of ADR will help strengthen the knowledge on patient safety and implement intervention strategies to reduce it. Objectives: The objectives of the study are as follows: 1. To study the pattern of adverse drug reactions of anticancer agents of patients admitted in the oncology ward. 2. To assess the causality, severity, and preventability of the adverse drug reactions observed. Methods: This was a cross-sectional, observational study carried out in 200 adult patients in the daycare center for chemotherapy. Details of ADRs noted in the previous and current cycles were noted. Causality assessment was done using Naranjo and WHO scales. For severity and preventability assessment, Hartwig Siegel and Modified Schumock Thorton scale were used, respectively. Conclusion: Alopecia was the most common ADR reported. Most of the ADRs could be causally related to drugs. These ADRs were mild to moderate in severity and were not preventable. There is a need to identify the underlying factors that predispose patients to these ADRs and target them in future research. Results: Out of the total 732 ADRs encountered, alopecia was the most common ADR. The average number of ADRs observed per patient was 3.66 + 1.59 (mean + SD). The maximum number of ADRs were seen in Paclitaxel-carboplatin 3 weekly regimen. Nausea and alopecia were the most common ADRs reported with most regimens. On causality assessment, 95 (12.97%) were definitely related according to Naranjo’s Causality scale, while 15.71% were certainly related according to the WHO scale. Of all the ADRs recorded, 47.81% were of moderate intensity, while 52.18% were of mild intensity. The majority of ADRs, i.e., 87.59%, were not preventable.

Introduction: Transurethral Resection of Prostate (TURP), using bipolar resectoscope, is performed using 0.9% Normal Saline (NS) as irrigating fluid. The NS is absorbed at about 10-30 mL per minute of resection time. The TURP averages 45 to 90 minutes of resection time. Thus, 450-2700 mL of NS is expected to be absorbed in this short time. Rapid administration of higher quantities of NS can cause hyperchloraemic acidosis, hyperkalaemia and negative protein balance. Aim: To detect changes in pH, serum electrolytes (serum bicarbonate, serum chloride, serum sodium, and serum potassium) and to record complications, if any, in patients undergoing bipolar TURP with 0.9% NS irrigation. Materials and Methods: This prospective cohort study was conducted at Lokmanya Tilak Municipal General Hospital, Mumbai, Maharashtra, India, from May 2017 to May 2018. Thirty patients undergoing saline bipolar TURP under subarachnoid block were studied. Preoperative and postoperative venous blood pH and serum electrolyte samples were collected. The quantity of NS used, duration of resection, and occurrence of complications were recorded and statistically analysed. Results: The mean age, mean gland size, resection time and volume of irrigation fluid used were 65.17±7.2 years, 64.9±30.85 cc, 60.67±14.17 minutes and 23.73±4.78 Litres, respectively. The mean preoperative pH of 7.33±0.047 fell by 0.03 postresection (p-value=0.02) and mean serum sodium increased from 139±3.65 meq/L to 142.2±3.60 meq/L, which was statistically significant (p-value=0.01). Serum bicarbonate, serum potassium, and serum chloride did not show any significant change. On relating the various intraoperative parameters with biochemical changes, a statistically significant but clinically insignificant association was found between the amount of irrigation fluid used and changes in serum sodium levels. Conclusion: The use of approximately 23.73 L NS in 60.67 mins of resection time and gland sizes up to 64.91 cc appear to produce no clinically significant changes in pH, serum electrolytes or complications with Bipolar TURP. However, further studies are needed to determine the acid base changes and safety with higher gland sizes requiring prolonged resection times and subsequently higher NS absorption.

Introduction Programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade is currently widely used in the treatment of metastatic NSCLC. Despite available biomarker stratification, clinical responses vary. Thus, the search for novel biomarkers with improved response prediction is ongoing. Previously, using mass cytometry or cytometry by time-of-flight (CyTOF), our group demonstrated that CD39+CD8+ immune cells represent tumor antigen-specific, cytotoxic T cells in treatment-naive NSCLC. We hypothesized that accurate quantitation of this T cell subset would predict immunotherapy outcome. Methods To translate this to a clinical setting, the present study compared CyTOF data with a range of clinically relevant methods, including conventional immunohistochemistry (IHC), multiplex IHC or immunofluorescence (mIHC), and gene expression assay by NanoString. Results Quantification using mIHC but not conventional IHC or NanoString correlated with the CyTOF results. The specificity and sensitivity of mIHC were then evaluated in a separate retrospective NSCLC cohort. CD39+CD8+ T cell proportion, as determined by mIHC, successfully stratified responders and nonresponders to PD-1 or PD-L1 inhibitors (objective response rate of 63.6%, compared with 0% for the negative group). This predictive capability was independent from other confounding factors, such as total CD8+ T cell proportion, CD39+ lymphocyte proportion, PD-L1 positivity, EGFR mutation status, and other clinicopathologic parameters. Conclusions Our results suggest that the mIHC platform is a clinically relevant method to evaluate CD39+CD8+ T cell proportion and that this marker can serve as a potential biomarker that predicts response to PD-1 or PD-L1 blockade in patients with NSCLC. Further validation in additional NSCLC cohorts is warranted.

Lead is a toxic heavy metal whose widespread use has caused extensive environmental contamination and health problems particularly in children and women of reproductive age. It affects multiple body systems, including the neurologic, hematologic, gastrointestinal, cardiovascular, and renal systems. Recent studies have shown that lead, has the potential to harm not only the young and the occupationally-exposed, but also older people and females with in the reproductive age. They may have been exposed to lead while working in unregulated occupations, or they may have encountered more lead in the environment on a daily basis. The Aim of the present study is to estimate urinary δ-ALA levels in heterogenous population of females in the reproductive age as an index of lead exposure. This cross- sectional study was conducted on randomly chosen 80 females of reproductive age from different areas of Mumbai with brief history related lead exposure. The morning first mid stream urine samples were collected with all standard precautions and analyzed for δ-ALA using modified Ehrlich’s reagent method. Out of the 80 samples – 69 samples (86.25%) urinary δ-ALA had levels above reference level i.e. (< 5mg/l). This is alarming. The reasons for this exposure may vary and we could not find a single cause for such a high level exposure, but we can say that it is closely related to the duration of exposure. Hence it is to conclude that it is difficult to stop lead exposure completely but by taking necessary precautions and providing health education we can reduce the lead exposure and its ill effects on health.

We read with great interest the article published by Zuo et al , which highlighted the presence of SARS-CoV-2 RNA in stool samples during active and convalescence phases of COVID-19 infection.1 However, no study has reported the presence of viral antigens within GI and hepatic organs during the convalescent phase. Using conventional immunohistochemistry, we detected SARS-CoV-2 nucleocapsid protein (NP) in the colon, appendix, ileum, haemorrhoid, liver, gallbladder and lymph nodes (figure 1A–K) from five patients who recovered from COVID-19, ranging from 9 to 180 days after testing negative for SARS-CoV-2 (online supplemental table 1). Notably, when multiple tissues were obtained from one patient (patients 1 and 4), all the tissues showed the presence of the viral antigen, suggesting widespread multiorgan involvement of the viral infection. Interestingly, for the colon, the viral antigen was only present in normal colonic crypts and polyps but not in the neoplastic tissues (figure 1Q). Similar negative staining in the hepatocellular carcinoma tumour region was also observed (figure 1R) albeit the positive staining in some of the scattered immune cells (figure 1D). Validating our findings, we detected SARS-CoV-2 spike protein (figure 1L–P) and RNA (figure 2B–F) in the above-mentioned tissues using conventional immunohistochemistry and RNAscope, respectively. However, we were unable to detect viral RNA in some patients’ tissues (online supplemental table 1), possibly because of higher RNA degradation rate as compared with protein and other patient-dependent factors such as disease severity, time since recovery and basal metabolic rate.### Supplementary data [gutjnl-2021-324280supp001.pdf] Figure 1 Immunohistochemical staining of the SARS-CoV-2 nucleocapsid and spike proteins in intestinal and hepatic tissues. (A and B) Positive SARS-CoV-2 nucleocapsid protein (NP) staining in colonic crypts (A) and appendix (B), both with a granular supranuclear cytoplasmic pattern. (C) positive SARS-CoV-2 NP staining in scattered immune cells …

Introduction: Malaria is one of the most common Parasitic infection prevalent worldwide especially in India, South Asia and Africa. About 250 million cases and approximately One million deaths of malaria reported per year worldwide. Oxidative stress (O.S.) has been implicated as possible mediator of thrombocytopenia in malarial patients. All eukaryotic cells, specially immune effector cells generate reactive oxygen species (ROS) and reactive nitrogen species (RNS) as a mean to combat invading microbes i.e. via the ' Oxidative burst', which increases the oxidative burden on the microbe to lethal levels. An excess of ROS such as superoxide anions, hydrogen peroxide (H2O2), hydroxyl radicals and /or RNS, such as nitric oxide (NO) and peroxynitrite (ONOO-) creates a potentially dangerous situation known as oxidative or nitrosative stress respectively. Aim: Present study aims to study the status of serum Malondialdehyde and Glutathione Peroxidase activity in hemolysate among the patients with Malaria. Materials and Methods: This is cross-sectional observational study on 200 non-treated malaria patients, compared with 100 normal individuals. Out of total 200 malaria patients 96 were plasmodium (P) vivax & 104 were P falciparum diagnosed cases. Results: Mean MDA level in the P. Vivax malaria cases was 12.29 + 0.32 micromole/L which was found to be higher compared to the controls with mean MDA level is 6.55+ 0.24 micromole/L, whereas the mean MDA level in P. Falciparum malaria cases was 13.5+ 0.18 micromole/L which was higher compared to the controls with mean MDA level of 6.55+ 0.24 micromole/L. Conclusion: The present study on malaria explains the role of oxidative stress in the pathophysiology of malaria which is a multifactorial phenomenon and represents an important aspect of the intricate and complex host- parasite relationship. Oxidative stress is aggravated by reduced effectiveness of the antioxidant defence system; hence it is advised to provide antioxidant supplements through diet that can reduce the disease severity and risk of death during infection.

Malaria is parasitic disease of humans caused by parasitic protozoan and genus plasmodium, widely present in tropical region. In the blood, the parasite travel to the liver to mature and reproduce. Oxidative stress is generated through the invasion of malarial parasites in human system. Malondialdehyde is a highly reactive compound is assayed in vivo as a biomarker of oxidative stress. Uric acid contributes to the pathology of human malaria by stimulating the production of cytokines from immune system. To estimate serum MDA & serum uric acid levels in patients with malarial infection and compare same with healthy individuals. This is a cross-sectional observational study, cases and controls were selected using random sampling method, attending hospital OPD. Study includes 50 laboratory diagnosed cases of malaria patients with equal age and sex matched controls. MDA was estimated using MDA - thiobarbituric acid method, uric acid was estimated by phosphotungstic acid method. Standardization of both the methods was carried out prior to experiment. There is generalized increase in serum MDA and uric acid levels in cases as compared to the control group.Shalaka S Prabhu, Dr. Sachin A Patharkar, Dr. Neelam J Patil, Jalinder B Sanap, Kalpana U Shinde, Rupa R Dalvi.

Background Laparoscopic surgery is performed under general anesthesia with mechanical ventilation, and a high-volume, low-pressure endotracheal tube (ETT) with a sealing cuff pressure about 20–30 cm of H2O is commonly used for a proper seal and avoidance of overinflation. Nitrous oxide (N2O) is an inhalational anesthetic that is used with oxygen in the ratio 50:50 for the maintenance of anesthesia if there is no facility of medical air. However, N2O increases the intracuff pressure of the tracheal tube due to diffusion of N2O in to cuff during general anesthesia. The present research was done to study the cuff pressure changes during laparoscopic surgeries with N2O anesthesia and to assess its variation during the various stages of surgery and also its correlation with position of the patient. Materials and methods A study was done in a tertiary-level hospital over a period of 1 year in 70 patients undergoing laparoscopic surgery. Endotracheal tube was inflated with incremental doses of 0.5 mL of air to a point where no leak on auscultation on the suprasternal area was noted. Cuff pressure measurement using cuff pressure monitor (Hand pressure gauge) was done at the time of first inflation of cuff up to 20–30 cm of H2O and airway pressure, along with total amount of air inflated was noted as “zero” reading. Thereafter, cuff pressure was measured at regular interval of 5 minutes. Cuff pressures and airway pressures were taken just prior to insufflation, 2 minutes after abdominal insufflation, thereafter every 15 minutes throughout surgery, and 2 minutes after desufflation and prior to extubation. Results Out of 70 patients, maximum patients were of the age-group of 20–50 years (78.5%). There was no statistically significant difference between the groups. Cuff pressure at the induction was kept in range of 20–30 cm of H2O. In this study, mean tracheal cuff pressure at baseline was 21.10 + 6.16 (p value of 0.207) and prior to insufflation was 21 + 7.13 (p value of 0.733). The cuff pressures at 2 minutes post insufflation (P2), P15, P30, P45, and P60 were 31.40 ± 12.54 cm of H2O, 25.79 ± 8.68 cm of H2O, 24.61 ± 7.37 cm of H2O, 23.83 ± 9.43 cm of H2O, and 24.63 ± 4.77 cm of H2O, respectively. p value was strongly significant showing a positive correlation between pneumo-peritoneum and cuff pressures. We could see the cuff pressure continuously increasing in successive readings. Post desufflation and prior to extubation, there was a fall in cuff pressure with mean cuff pressure being 17.24 + 5.32 cm of H2O and 15.27 + 4.00 cm of H2O, respectively, which also suggests that cuff pressures increased with pneumoperitoneum. Conclusion Use of N2O increases the cuff pressure (31.4 + 12.54 cm of H2O), especially immediately post-insufflation (35.54 + 12.06 cm of H2O), more so in head low position (36.28 + 12.13 cm of H2O). Mean airway pressure (Ppeak) also increased with pneumoperitoneum (22.60 + 4.38 cm of H2O). The regular monitoring of endotracheal tube cuff pressure should be a part of regular safe practice of anesthesia, and use of handy device like hand pressure gauge should be implemented in regular practice where N2O is used. How to cite this article Narendra HR, Nerurkar A, Sasidharan S. Observational Analysis of Changes in Endotracheal Tube Cuff Pressure During Laparoscopic Surgery. J Med Acad 2020;3(2):46–49.

International audience; Background: Global HIV-1 genetic diversity and evolution form a major challenge to treatment and prevention efforts. An increasing number of distinct HIV-1 recombinants have been identified worldwide, but their contribution to the global epidemic is unknown. We aimed to estimate the global and regional distribution of HIV-1 recombinant forms during 1990-2015.Methods: We assembled a global HIV-1 molecular epidemiology database through a systematic literature review and a global survey. We searched the PubMed, Embase (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) databases for HIV-1 subtyping studies published from Jan 1, 1990, to Dec 31, 2015. Unpublished original HIV-1 subtyping data were collected through a survey among experts in the field who were members of the WHO-UNAIDS Network for HIV Isolation and Characterisation. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. Countries were grouped into 14 regions and analyses were done for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV in each country to generate regional and global estimates of numbers and proportions of HIV-1 recombinants in each time period. The systematic review is registered with PROSPERO, CRD42017067164.Findings: Our global data collection yielded an HIV-1 molecular epidemiology database of 383 519 samples from 116 countries in 1990-2015. We found that the proportion of recombinants increased over time, both globally and in most regions, reaching 22·8% (7 978 517 of 34 921 639) of global HIV-1 infections in 2010-15. Both the proportion and the number of distinct CRFs detected increased over time to 16·7% and 57 CRFs in 2010-15. The global and regional distribution of HIV-1 recombinants was diverse and evolved over time, and we found large regional variation in the numbers (0-44 CRFs), types (58 distinct CRFs), and proportions (0-80·5%) of HIV-1 recombinants. Globally, CRF02_AG was the most prevalent recombinant, accounting for 33·9% (2 701 364 of 7 978 517) of all recombinant infections in 2010-15. URFs accounted for 26·7% (2 131 450 of 7 978 517), CRF01_AE for 23·0% (1 838 433), and other CRFs for 16·4% (1 307 270) of all recombinant infections in 2010-15. Although other CRFs accounted for small proportions of infections globally (

The aim of the study was to compare interpositional arthroplasty using a dermis fat graft with gap arthroplasty in the management of ankylosis of the temporomandibular joint (TMJ). We organised a prospective randomised study of 22 patients who presented with ankylosis of the TMJ. They were randomised to be treated with either plain gap arthroplasty or dermis fat arthroplasty, and the predictor variable was the method of treatment. The primary outcome variables were mouth opening and pain on jaw exercises. Pain and interincisal opening were measured on day 5, day 14, at the end of one month, and at six months, one year, two years, and three years. There was a significant difference between the two groups on two occasions: postoperative day 5 (p=0.013) and at one year (p=0.018). The mean (SD) scores for mouth-opening were higher in the dermis fat group at all times (41.20 (4.69) mm compared with 39.50 (2.46) mm in gap arthroplasty at two years, and 41.40 (3.60) mm compared with 38.9 (2.02) mm at three years). The visual analogue pain scores were also lower in the dermis fat graft group. The groups showed similar results at the end of three years follow up, with no significant difference in mouth opening. We conclude therefore that the two techniques have similar outcomes in the management of ankylosis of the TMJ.

Highlights • It is a case study of an immunocompromised patients affected by Mucormycosis which is - a profoundly mortal fungal infection. • In order to restore the function, enhance the cosmetic appearance and quality of life of the patient, surgical intervention is often necessary to correct the various pathologies affecting the patients. • This paper highlights the significance of prompt diagnosis and urgent treatment, especially among high-risk patients, of this potentially lethal phenomenon and the surgical procedure undertaken to remove the disease afecting the person and improve the patient's overall health. • The management of our patient demonstrates the need for an early visual identification and diagnosis approach that is multidisciplinary, multi-factorial and multi-faceted., Introduction Mucormycosis is a rare, rapidly progressive and a fulminant, life-threatening, opportunistic infection. Although it most commonly manifests in diabetic patients, its presence in other immunologically compromised patients cannot be ruled out. Its etiology is saprophytic fungal organisms, with rhizopus being the most common causative organism. Clinically the disease is marked by a partial loss of neurological function and a progressive necrosis due to the invasion of the organisms into the blood vessels causing a lack of blood supply. The disease may progress to involve the cranium thereby increasing the mortality rate. The first line of management in mucormycosis is antifungal therapy which may extend and also include surgical management. Presentation of case Authors present here two patients with mucormycosis affecting the maxillofacial region, that were treated by including both medical and surgical lines of management. Discussion This report aims to highlight the importance of prompt diagnosis and urgent management of this potentially fatal phenomenon, particularly among high-risk individuals. Conclusion This case report intensifies the importance of considering mucormycosis as a possible diagnosis in spontaneous necrotic soft tissue lesions of the face, especially in an immunocompromised patient.

Background COVID‐19 has become a pandemic, but its reported characteristics and outcomes vary greatly amongst studies. Objectives We determined pooled estimates for clinical characteristics and outcomes in COVID‐19 patients including subgroups by disease severity (based on WHO Interim Guidance Report or IDSA/ATS criteria) and by country/region. Methods We searched Pubmed, Embase, Scopus, Cochrane, Chinese Medical Journal, and preprint databases from January 1, 2020 to April 6, 2020. Studies of laboratory confirmed COVID‐19 patients with relevant data were included. Two reviewers independently performed study selection and data extraction. Results From 6,007 articles, 212 studies from 11 countries/regions involving 281,461 individuals were analyzed. Overall, mean age was 46.7 years, 51.8% were male, 22.9% had severe disease, and mortality was 5.6%. Underlying immunosuppression, diabetes, and malignancy were most strongly associated with severe COVID‐19 (coefficient=53.9, 23.4, 23.4, respectively, all p

Background: Lead toxicity is a significant environmental hazard and has widespread ill effects on human body. In this study we detected the lead exposure by measuring urinary delta aminolevulinic acid levels. The activity of delta aminolevulinic acid dehydratase enzyme is inhibited significantly by lead, which leads to an increase in urinary δ- ALA excretion. Hence we can use estimation of urinary δ-ALA levels as a surrogate marker of lead exposure in pottery workers. Aim: To estimate the urinary delta aminolevulinic acid levels in pottery workers as an index of lead exposure. Materials and Methods: The study was done on 85 pottery workers of age group between 18 to 50 years with their brief history related to lead exposure. Their urine samples were analysed for δ-ALA by Ehrlich method. Results: According to our observation, it was found that out of 85 urine samples; 58 samples showed increased urinary δ-ALA levels (68.23%). Conclusion: We conclude that the prevalence of lead exposure in pottery workers in Mumbai is very high. Good hygienic practices and necessary precautions should be followed to avoid its ill effects on human body.

Background: Lead poisoning is a serious and sometimes fatal condition. It occurs when lead builds up in the body. Students exposed to lead by eating junk foods wrapped in newspaper, the licking of fingers for turning the photocopies, book pages, printout etc. and use of same fingers for eating purpose. Additionally young population get exposed to lead by use of Kohl or Kajal eyeliners, some traditional ethnic medicines, time spent at firing ranges and some hobbies like wall paintings or jobs related to plumbing and soldering. Damage caused by lead poisoning cannot be reversed. Lead inhibits necessary enzymes required for heme synthesis, and this result in increased levels of delta-aminolevulinic acid (δ-ALA) excretion through urine. Aim: To Estimate the urinary δ-ALA levels in the students of age group 15 to 25 years as an index of lead exposure. Study Design: This is a cross-sectional study in Mumbai from a suburban locality. Methodology: The study was done on 70 students of age group between 15 years and 25 years with their brief history related to lead exposure. Their urine samples were analyzed for δ-ALA by using Ehrlich reagent. Results: According to our observation, out of 70 students 46 student’s (65.71%)urine samples shown δ-ALA level above reference level and remaining 24 (34.28%) were considered as below reference level. Conclusion: The prevalence of lead exposure among our study population is 65.71%. Clinical Significance: We conclude that there is high prevalence of lead exposure in students of age group 15 to 25 years in Mumbai and necessary precautions need to be taken to avoid detrimental effects of lead poisoning.

Objective An increasing number of vocal fold cysts excised, as compared to polyps, over the last decade led us to review these cases. We found a statistically significant increase in cysts excised as compared to polyps, over the latter 5-year period (2013-2017). This prompted us to analyze possible factors responsible for this increase. We also performed a histological study of the normative distribution pattern of seromucinous glands in the apparently normal vocal folds. Methods A retrospective review of all cysts and polyps excised over a 10-year period was performed. Patient demographics, air-pollution levels, videostroboscopic findings and histologic analysis of pathology were reviewed. Findings were compared between the initial and latter 5-year period of all cysts excised. The second part of the study entailed a histological study of the presence and distribution pattern of seromucinous glands in 40 apparently normal fresh frozen cadaver vocal folds. Results There was a statistically significant (P = .035) increase of mucous retention cysts excised as compared to polyps over the latter 5-year period. Decreased laryngeal hydration was a significant associated finding in cysts excised over the decade as compared to polyps. Striking zone lesions, suggestive of vocal abuse, were seen in a majority of patients of both polyps and cysts excised over the decade. Air pollution had significantly increased in India over the latter 5-year period. Vocal fold histology in cadavers revealed a presence of seromucinous glands in 32.50% (13/40) with 25.00% (10/40) present in the Superficial Lamina Propria (SLP). Conclusion Decreased laryngeal hydration, vocal abuse and mucous glands present in the SLP may be predisposing factors towards mucous retention cyst formation. An increase in number of these cysts excised over the latter 5-year period was seen as was increased air pollution. Level of evidence 3b for the first part of study and NA for the second part of the study Laryngoscope, 130:986-991, 2020.

Purpose: Advanced breast cancer (ABC) has not been subjected to the same degree of molecular scrutiny as early primary cancer. Breast cancer evolves with time and under the selective pressure of treatment, with the potential to acquire mutations with resistance to treatment and disease progression. To identify potentially targetable mutations in advanced breast cancer, we performed prospective molecular characterization of a cohort of patients with ABC. Experimental Design: Biopsies from patients with advanced breast cancer were sequenced with a 41 genes targeted panel in the ABC Biopsy (ABC-Bio) study. Blood samples were collected at disease progression for circulating tumor DNA (ctDNA) analysis, along with matched primary tumor to assess for acquisition in ABC in a subset of patients. Results: We sequenced 210 ABC samples, demonstrating enrichment compared with primary disease for potentially targetable mutations in HER2 (in 6.19% of samples), AKT1 (7.14%), and NF1 (8.10%). Of these enriched mutations, we show that NF1 mutations were frequently acquired in ABC, not present in the original primary disease. In ER-positive cancer cell line models, loss of NF1 resulted in endocrine therapy resistance, through both ER-dependent and -independent mechanisms. NF1 loss promoted ER-independent cyclin D1 expression, which could be therapeutically targeted with CDK4/6 inhibitors in vitro. Patients with NF1 mutations detected in baseline circulating tumor DNA had a good outcome on the CDK4/6 inhibitor palbociclib and fulvestrant. Conclusions: Our research identifies multiple therapeutic opportunities for advanced breast cancer and identifies the previously underappreciated acquisition of NF1 mutations.

SUMMARYMalaria-causing P. vivax parasites can linger in the human liver for weeks to years, and then reactivate to cause recurrent blood-stage infection. While an important target for malaria eradication, little is known about the molecular features of the replicative and non-replicative states of intracellular P. vivax parasites, or the human host-cell responses to them. Here, we leverage a bioengineered human microliver platform to culture Thai clinical isolates of P. vivax in primary human hepatocytes and conduct transcriptional profiling of infected cultures. By coupling enrichment strategies with bulk and single-cell analyses, we captured both parasite and host transcripts in individual hepatocytes throughout the infection course. We defined host- and state-dependent transcriptional signatures and identified previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We found that infection suppresses transcription of key hepatocyte function genes, and that P. vivax elicits an innate immune response that can be manipulated to control infection. Our work provides an extendible framework and resource for understanding host-parasite interactions and reveals new insights into the biology of malaria dormancy and transmission.

The impact of COVID-19 disease on health and economy has been global, and the magnitude of devastation is unparalleled in modern history. Any potential course of action to manage this complex disease requires the systematic and efficient analysis of data that can delineate the underlying pathogenesis. We have developed a mathematical model of disease progression to predict the clinical outcome, utilizing a set of causal factors known to contribute to COVID-19 pathology such as age, comorbidities, and certain viral and immunological parameters. Viral load and selected indicators of a dysfunctional immune response, such as cytokines IL-6 and IFNα, which contribute to the cytokine storm and fever, parameters of inflammation d-dimer and ferritin, aberrations in lymphocyte number, lymphopenia, and neutralizing antibodies were included for the analysis. The model provides a framework to unravel the multi-factorial complexities of the immune response manifested in SARS-CoV-2 infected individuals. Further, this model can be valuable to predict clinical outcome at an individual level, and to develop strategies for allocating appropriate resources to mitigate severe cases at a population level.

Isolated Fungal Laryngitis (FL) has recently shown an increased incidence globally and is now being reported even in immunocompetent individuals. In our Voice Clinic we have documented an increasing number of cases of FL, specifically laryngeal candidiasis, with the lesion over the striking zone (anterior 1/3rd posterior—2/3rd) of vocal folds. Our objective was to study the sites of involvement of FL within the glottis along with a review of literature. A 4 year retrospective study was performed by reviewing clinical and stroboscopic recordings of all patients diagnosed as FL at our Voice clinic. Age, gender, presenting complaints, co-morbidities, history of steroid intake orally or via inhalation and stroboscopic findings were noted as was response to antifungals and duration of treatment. A total of 55 cases were diagnosed with FL (all laryngeal candidiasis) between 2016 and 2019. Majority of them were immunocompetent, middle aged (41–60 years) males. Hoarseness was the most common presenting complaint. On stroboscopy, the striking zone involvement was seen in 89.1% cases. On comparing site of involvement a chi-square value of 115.58; p

Using genomics, bioinformatics and statistics, herein we demonstrate the effect of statewide and nationwide quarantine on the introduction of SARS-CoV-2 variants of concern (VOC) in Hawai’i. To define the origins of introduced VOC, we analyzed 260 VOC sequences from Hawai’i, and 301,646 VOC sequences worldwide, deposited in the GenBank and global initiative on sharing all influenza data (GISAID), and constructed phylogenetic trees. The trees define the most recent common ancestor as the origin. Further, the multiple sequence alignment used to generate the phylogenetic trees identified the consensus single nucleotide polymorphisms in the VOC genomes. These consensus sequences allow for VOC comparison and identification of mutations of interest in relation to viral immune evasion and host immune activation. Of note is the P71L substitution within the E protein, the protein sensed by TLR2 to produce cytokines, found in the B.1.351 VOC may diminish the efficacy of some vaccines. Based on the phylogenetic trees, the B.1.1.7, B.1.351, B.1.427, and B.1.429 VOC have been introduced in Hawai'i multiple times since December 2020 from several definable geographic regions. From the first worldwide report of VOC in GenBank and GISAID, to the first arrival of VOC in Hawai’i, averages 320 days with quarantine, and 132 days without quarantine. As such, the effect of quarantine is shown to significantly affect the time to arrival of VOC in Hawai’i, both during and following quarantine. Further, the collective 2020 quarantine of 43-states in the United States demonstrates a profound impact in delaying the arrival of VOC in states that did not practice quarantine, such as Utah. Our data demonstrates that at least 76% of all definable SARS-CoV-2 VOC have entered Hawai’i from California, with the B.1.351 variant in Hawai’i originating exclusively from the United Kingdom. These data provide a foundation for policy-makers and public-health officials to apply precision public health genomics to real-world policies such as mandatory screening and quarantine.

Introduction: Tobacco chewing is a serious oral health problem in India responsible for halitosis, periodontitis, sub mucus fibrosis, leukoplakia and oral cancer. There is a need to understand the oral microbiological changes in tobacco chewers. Aim and Objective: To find out the changes in oral microbiota in tobacco chewing patients and patients with associated oral cancer. Materials and Methods: A case control study on 102 patients was conducted over a period of 2 months. Case group included subjects with tobacco chewing habits and presence of leukoplakia and oral cancer while control group included subjects with no tobacco chewing habits. Oral swabs collected were microscopically examined and grown on routine culture media- Blood Agar, Nutrient Agar and McConkey’s Agar. After obtaining the complete data of different bacteria isolated, a statistical analysis was made comparing the isolates from case and control group. Results: Streptococci spp. and Coagulase Negative Staphylococcispp (CONS) forms a part of normal oral flora, which was found in 79% of the control isolates but only in 49% of the case isolates. This result of normal flora being reduced in case group was statistically significant (p group, other species- Enterococci, Pseudomonas and Klebsiella were found in only 21% of control isolates while 51% of cases showed such result but Acinetobacter spp, Proteus spp and Citrobacter freundii were also isolated. Conclusion: Tobacco chewing is associated with a disruption of normal oral flora and a consequent increase in other organisms making the oral cavity more prone to ailments. Keywords: Oral flora, Tobacco chewers.

Objective: To evaluate the prescription pattern of chronic kidney disease patients undergoing haemodialysis in both hospitals. Methods: The study was carried out in a tertiary care and a private hospital for a period of nine months. Chronic kidney disease patients on maintenance haemodialysis for at least one month were included. Details like sociodemographic and clinical characteristics, past medication history, comorbidities and current medications were noted in self-pre-designed Patient Proforma. Mean ± standard deviation and percentages and relevant statistical tests like Chisquare test was used. Results: Majority of the patients belonged to middle socio-economic class in private hospital and lower-middle class in tertiary hospital. Maximum were unemployed (50.60%, 36%), married (90.36%, 88%) and had high school qualification (62.65%, 45.33%). About 78 (93.97%) patients were covered with insurance/health scheme in tertiary hospital and 39 (52%) in private hospital. Hypertension was found to be the leading cause in tertiary and private hospital. Calcium channel blockers (77.10%, 53.30%) were highly prescribed in both the hospitals. Erythropoietin (69.80%), calcium acetate (21.70%) and anti-diabetics (Insulin 10.84%) in tertiary hospital, whereas newer and costlier drugs like Darbepoetin, Iron preparations and Lanthanum carbonate were prescribed in private hospital. Conclusion: Socioeconomic status led to variation in prescription patterns among both hospitals as newer and costlier drugs like Lanthanum carbonate, Sevelamer and Darbepoetin were prescribed only in private hospital. Key words: Chronic kidney disease, Polypharmacy, Prescription pattern, Socioeconomic status.

Introduction: A surgical site infections (SSI) are a 3rd most common nosocomial infection and is responsible for morbidity, mortality and increased healthcare costs. Aims and Objectives: The main aim of this study is to identify the isolates causing surgical site infections and its anti-microbial susceptibility pattern. Materials and Methods: A total 50 cases of surgical site infections were taken for the study. The suspected samples were processed by using standard microbiological methods. The modified Kirby-Bauer’s disc diffusion method was used for antibiotic susceptibility pattern. The isolates of Enterobacteriaceae family were initially screened for ESBL production and were further confirmed by Double Disk Synergy Test as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Reference strains of E. coli (ATCC 25922), P. aeruginosa (ATCC-27853), S. aureus (ATCC 25923) and Klebsiella 700603 were used as controls. Result: Out of 50 samples, 19(38%) were culture positive and total 23 organisms were isolated. Pseudomonas aeruginosa 9 (39.13%) was the most common organism isolated, followed by Klebsiella spp. 5 (21.73%), Staphylococcus aureus 3 (13.04%). Most of the Gram-negative isolates were sensitive to imipenem and meropenem followed by piperacillin-tazobactam. Gram-positive organisms were found to be more sensitive to levofloxacin, linezolid and vancomycin. ESBL production was seen among 44.44% isolates of Enterobacteriaceae family. Conclusion: The rate of infection reflects on patient's care and standard of treatment in any hospital. Thus, better stewardship of SSI is required with accurate antibiotic policies. Periodic monitoring of etiology and antimicrobial susceptibility in the community and hospital settings is recommended. Keywords: Surgical site infection, Bacteriological profile, Antibiotic susceptibility test, ESBL (Extended Spectrum Beta-Lactamase).

Background Accurate diagnosis of malaria is important for effective disease management and control. In Cameroon, presumptive clinical diagnosis, thick-film microscopy (TFM), and rapid diagnostic tests (RDT) are commonly used to diagnose cases of Plasmodium falciparum malaria. However, these methods lack sensitivity to detect low parasitaemia. Polymerase chain reaction (PCR), on the other hand, enhances the detection of sub-microscopic parasitaemia making it a much-needed tool for epidemiological surveys, mass screening, and the assessment of interventions for malaria elimination. Therefore, this study sought to determine the frequency of cases missed by traditional methods that are detected by PCR. Methods Blood samples, collected from 551 febrile Cameroonian patients between February 2014 and February 2015, were tested for P. falciparum by microscopy, RDT and PCR. The hospital records of participants were reviewed to obtain data on the clinical diagnosis made by the health care worker. Results The prevalence of malaria by microscopy, RDT and PCR was 31%, 45%, and 54%, respectively. However, of the 92% of participants diagnosed as having clinical cases of malaria by the health care worker, 38% were malaria-negative by PCR. PCR detected 23% and 12% more malaria infections than microscopy and RDT, respectively. A total of 128 (23%) individuals had sub-microscopic infections in the study population. The sensitivity of microscopy, RDT, and clinical diagnosis was 57%, 78% and 100%; the specificity was 99%, 94%, and 17%; the positive predictive values were 99%, 94%, and 59%; the negative predictive values were 66%, 78%, and 100%, respectively. Thus, 41% of the participants clinically diagnosed as having malaria had fever caused by other pathogens. Conclusions Malaria diagnostic methods, such as TFM and RDT missed 12–23% of malaria cases detected by PCR. Therefore, traditional diagnostic approaches (TFM, RDT and clinical diagnosis) are not adequate when accurate epidemiological data are needed for monitoring malaria control and elimination interventions.

Summary The coexistence of immune-mediated inflammatory diseases with depression has long been recognised. Data that illustrate the intimate associations between peripheral and brain immune responses raise the possibility of shared pathophysiological mechanisms. These associations include the negative effects of proinflammatory cytokines on monoaminergic neurotransmission, neurotrophic factors, and measures of synaptic plasticity. The evidence supporting this association is accumulating and includes findings from clinical trials of immunomodulatory therapy, indicating that these interventions can provide benefits to mental health independent of improvements in physical disease scores. In this Review, we assess this evidence in relation to rheumatoid arthritis and depression, with a focus on innate immune and molecular responses to inflammation, and discuss the challenges of assessing causation in this population, acknowledging the difficulty of assessing the confounding and contributory effects of pain and fatigue. We also discuss how future clinical and preclinical research might improve diagnosis of depression in people with rheumatoid arthritis and shed light on mechanisms that could be substrates for therapeutic interventions.

Setting: A prospective observational study conducted in Medical college hospital, in a high-TB- prevalence region of northern Telangana, India. Objective: To know the diagnostic role of Xpert MTB/RIF assay in bronchoalveolar lavage fluid (BALF) in sputum-scarce, suspected pulmonary tuberculosis (PTB) patients. Design: Study period was between October 2014 and March 2017. Suspected pulmonary tuberculosis patients aged 15 years or more, who were sputum-scarce and conforming to the inclusion criteria were submitted to bronchoscopy. BALF thus obtained was submitted to smear for acid fast bacilli (AFB) and Xpert MTB/RIF assay as index tests along with culture for Mycobacterium tuberculosis complex (MTBC). Culture for M. tuberculosis complex was considered as gold standard for the diagnosis of PTB. The sensitivity, specificity and predictive values were calculated for smear AFB and Xpert MTB/RIF assay. Results: 56 of the 81 patients were included and evaluated in the final analysis. In 10 of these 56 patients PTB was confirmed by culture positivity. The sensitivity and specificity of Xpert MTB/RIF assay was 90% (9/10,95%CI 59.6- 98.2) and 52.2% (24/46, 95%CI 38. 1-65.9) respectively and that of the smear AFB was 60% (6/10, 95%CI 31.2–83.1) and 67.4% (31/46, 95%CI 53.0–79.1). All the patients considered ‘probable’ PTB (pending culture results), were administered antituberculous treatment and showed complete clinicoradiological improvement on follow up. Three of the 31 Xpert MTB/RIF positive patients were detected as resistance to rifampicin (RR). Conclusions: Xpert MTB/RIF assay of BALF in the study cohort provides rapid diagnosis of Mycobacterium tuberculosis, and detection of rifampicin resistance at the very outset, aiding in selection of appropriate ATT regimen. In this context, it can be recommended as the first line investigation. Xpert MTB/RIF assay aided by HRCT Chest and suggestive clinical presentation may be helpful in early institution of ATT especially in smear negative, culture negative cases. Keywords: Xpert MTB/RIF assay, BAL fluid, Tuberculosis

The embryonic gut tube is a cylindrical structure from which the respiratory and gastrointestinal tracts develop1. Although the early emergence of the endoderm as an epithelial sheet2,3 and later morphogenesis of the definitive digestive and respiratory organs4-6 have been investigated, the intervening process of gut tube formation remains relatively understudied7,8. Here we investigate the molecular control of macroscopic forces underlying early morphogenesis of the gut tube in the chick embryo. The gut tube has been described as forming from two endodermal invaginations-the anterior intestinal portal (AIP) towards the rostral end of the embryo and the caudal intestinal portal (CIP) at the caudal end-that migrate towards one another, internalizing the endoderm until they meet at the yolk stalk (umbilicus in mammals)1,6. Migration of the AIP to form foregut has been descriptively characterized8,9, but the hindgut is likely to form by a distinct mechanism that has not been fully explained10. We find that the hindgut is formed by collective cell movements through a stationary CIP, rather than by movement of the CIP itself. Further, combining in vivo imaging, biophysics and mathematical modelling with molecular and embryological approaches, we identify a contractile force gradient that drives cell movements in the hindgut-forming endoderm, enabling tissue-scale posterior extension of the forming hindgut tube. The force gradient, in turn, is established in response to a morphogenic gradient of fibroblast growth factor signalling. As a result, we propose that an important positive feedback arises, whereby contracting cells draw passive cells from low to high fibroblast growth factor levels, recruiting them to contract and pull more cells into the elongating hindgut. In addition to providing insight into the early gut development, these findings illustrate how large-scale tissue level forces can be traced to developmental signals during vertebrate morphogenesis.

Limbal stem cell deficiency (LSCD) is a disease resulting from the loss or dysfunction of epithelial stem cells, which seriously impairs sight. Autologous limbal stem cell transplantation is effective in unilateral or partial bilateral disease but not applicable in total bilateral disease. An allogeneic source of transplantable cells for use in total bilateral disease can be obtained from culture of donated cadaveric corneal tissue. We performed a controlled multicenter study to examine the feasibility, safety, and efficacy of allogeneic corneal epithelial stem cells in the treatment of bilateral LSCD. Patients were randomized to receive corneal epithelial stem cells cultured on amniotic membrane (AM): investigational medicinal product (IMP) or control AM only. Patients received systemic immunosuppression. Primary endpoints were safety and visual acuity, secondary endpoint was change in composite ocular surface score (OSS). Sixteen patients were treated and 13 patients completed all assessments. Safety was demonstrated and 9/13 patients had improved visual acuity scores at the end of the trial, with no significant differences between IMP and control groups. Patients in the IMP arm demonstrated significant, sustained improvement in OSS, whereas those in the control arm did not. Serum cytokine levels were measured during and after the period of immune suppression and we identified strongly elevated levels of CXCL8 in the serum of patients with aniridia, which persisted throughout the trial. This first randomized control trial of allogeneic corneal epithelial stem cells in severe bilateral LSCD demonstrates the feasibility and safety of this approach. tem Cells Translational Medicine 2019;8:323–331