Epidemiology of cancers among older adults in India: findings from the National Cancer Registry Programme.

OBJECTIVE: This study describes the epidemiology, clinical extent of disease at diagnosis and treatment modalities of cancer among older adults (aged 60 years and older) in India. STUDY DESIGN: Secondary data analysis of the National Cancer Registry Programme, which includes 28 Population-Based Cancer Registries (PBCRs) and 96 Hospital-Based Cancer Registries (HBCRs). METHODS: PBCR data were used to estimate the incidence in terms of crude rate (CR), age-adjusted incidence rate (AAR), age-specific rate (ASpR) and cumulative risk. Trends in the AAR were calculated with the Annual Percentage Change (APC) using join-point regression. HBCR data were used to describe the clinical extent of the disease at diagnosis and the treatment modalities. RESULTS: There is a wide heterogeneity across the country for the incidence of cancer and for the leading cancer sites among older adults. Males had a higher incidence rate compared to females in the majority of the registries. Aizawl had the highest AARs among both genders (males: 1388.8; females: 1033.0). Females had the highest ASpR at 65-69 years (482.8), whereas for males it was above 75 years (710.4). Cervical, stomach and oesophageal cancers were on the decline. The incidence of cancer among older adults was estimated to increase by 13.5% in 2025 as compared to 2020. CONCLUSION: The increasing cancer incidence among older adults in India poses a huge burden on the health system. There is a need to increase their participation in clinical trials, advocating comprehensive geriatric assessment and strengthening geriatric oncology within programs addressing older adult's care to deal with the rising cancer burden on the health system borne by them.

Maternal and neonatal characteristics, operative details and outcomes in COVID-19 positive parturients undergoing cesarean sections: A retrospective observational study.

Background and Aims: There is a marked inclination towards cesarean sections as the preferred mode of delivery in parturients with COVID-19 disease. However, the challenges associated with planning and performing a surgery in the COVID-19 setup are considerable. These factors may lead to widespread changes in obstetric decision-making, operative planning, and perioperative outcomes. Thus, our study aimed to study the clinical and logistical factors involved in cesarean sections in COVID-19 parturients. Material and Methods: This was a retrospective observational study performed at a dedicated COVID-19 tertiary care center in India. All women undergoing cesarean section in the specially earmarked operating room between 1st May 2020 and 31st December 2020 were included in the study. The clinical characteristics, operative details, and neonatal details, along with maternal and fetal outcomes were noted and analyzed. Results: A total of 44 women underwent cesarean section during the study period, with elective and emergency surgeries numbering 22 each. No indication, apart from COVID-19 status, was listed in over one-fourth of the women (13/44). The most common preoperative comorbidity was hypothyroidism (12/44). Median surgical duration was 117.5 min (IQR 100-133), with a median of 7.5 (IQR 6-8.25) healthcare personnel in the OT. Over one-fourth (12/44) of the delivered babies had low birth weight, while 4.5% (2/44) tested positive for SARS-CoV-2. Conclusion: COVID-19 status alone continues to be a common indication for cesarean section. Operative time is increased, but the number of healthcare personnel involved can be trimmed with proper planning. Maternal and fetal outcomes are largely positive, with low transmission rates, but a considerable proportion of low-birth-weight neonates.

Epigenetic modulation and apoptotic induction by a novel imidazo-benzamide derivative in human lung adenocarcinoma cells.

PURPOSE: Lung cancer is the most commonly diagnosed and leading cause of cancer death worldwide. Imidazo-benzamides are considered to be good anti-cancer agents. The present study was aimed to investigate the cytotoxicity of a novel imidazo-benzamide derivative N-(2-(3-(tert-butyl)ureido)ethyl)-4-(1H-imidazol-1-yl)benzamide (TBUEIB) in lung cancer cell line A549. METHODS: The antiproliferative activity of TBUEIB was investigated using MTT, LDH and trypan blue assay. The apoptotic potential was investigated using various staining techniques and further confirmed by DNA fragmentation assay and western blotting. RESULTS: TBUEIB inhibited fifty precent A549 cells at a dose of 106 µM. The novel compound was found to exert a modulatory effect on apoptotic marker caspase-3 as well as epigenetic regulatory proteins like DNA Methyltransferase 1 (DNMT1). In silico studies with the compound and other epigenetic proteins such as Histone deacetylase (HDAC) and ubiquitin-like with PHD (plant homeodomain) and RING (Really Interesting New Gene) finger domains 1(UHRF1) showed good modulatory effects. CONCLUSION: The overall results obtained in the study conclude that the novel compound TBUEIB has potential anti-cancer activities, mainly by targeting the expression of DNMT1 enzyme, which may have re-activated the major tumor suppressor genes involved in the cell cycle, leading to the apoptosis of the cancer cells. The results also indicate that the compound has more than one target in the epigenetic pathway implying that the compound may be a potential multi-target compound.

Secondary colonic stent insertion in acute large bowel obstruction following primary stent failure.

INTRODUCTION: Colonic stent insertion has been shown to be an effective treatment for patients with acute large bowel obstruction, either as a bridge to surgery or as definitive treatment. However, little is known of the role of secondary stent insertion following primary stent failure in patients considered inappropriate or high risk for emergency surgery. METHODS: Fourteen patients presenting with acute large bowel obstruction who had previously been treated with colonic stent insertion were studied. All underwent attempted placement of a secondary stent. RESULTS: Technical deployment of the stent was accomplished in 12 patients (86%) but only 9 (64%) achieved clinical decompression. Successful deployment and clinical decompression of a secondary stent was associated with older age (p=0.038). Sex, pathology, site of obstruction, duration of efficacy of initial stent and cause of primary failure were unrelated to outcome. No procedure related morbidity or mortality was noted following repeated intervention. CONCLUSIONS: Secondary colonic stent insertion appears an effective, safe treatment in the majority of patients presenting with acute large bowel obstruction following failure of a primary stent.

Calcium ionophore enhanced developmental competence and apoptotic dynamics of goat parthenogenetic embryos produced in vitro.

Parthenogenetically developed embryos are efficient sources of in vitro embryo production, having less ethical issue and being useful for investigating culture conditions/treatments, early developmental, genomic studies, and homonymous source of stem cells. Keeping its advantages in mind, we aimed to study the effects of different activating agents on embryo production and its quality and gene expression. In the present study, 1348 immature oocytes recovered were parthenogenetically developed to embryos. Usable-quality immature oocytes were collected by puncturing the surface follicles and matured in in vitro maturation (IVM) medium for 27 h in a humidified 5% CO2 incubator at 38.5°C. The matured oocytes were parthenogenetically activated by exposure to 5 µM calcium ionophore for 5 min or 7% ethanol for 7 min sequentially followed by 4 h incubation in 2 mM 6-DMAP and then in vitro cultured (IVC) in RVCL/G-2 medium for 8 days. Matured oocytes were activated by calcium ionophore, the cleavage rate observed was 76.67 ± 3.47%, and further they developed into 4-cell, 8-16-cell, morula, blastocyst, and hatched blastocyst with 85.30 ± 1.57%, 70.60 ± 2.00%, 45.05 ± 2.66%, 22.89 ± 2.40%, and 5.70 ± 1.97%, respectively. Whereas ethanol-activated oocytes showed cleavage rate of 87.60 ± 1.70% and further culture developed into 4-cell, 8-16 cell, morula, blastocyst, and hatched blastocyst with 86.14 ± 1.03%, 71.56 ± 2.21%, 40.90 ± 2.45%, 19.02 ± 1.26%, and 2.22 ± 0.38%, respectively. Blastocyst developed from calcium ionophore-activated oocytes showed significantly (P < 0.05) higher total cell number (282.25 ± 27.02 vs 206.00 ± 40.46) and a lower apoptotic index (2.42 ± 0.46 vs 4.07 ± 1.44) than blastocyst developed from ethanol-activated oocytes. The relative expression of anti-apoptotic genes (BCL2, BCL2A1, MCL) at different stages of embryos produced by either calcium ionophore or ethanol activation was found to be increased in earlier stages and decreased in later stages of embryonic development. Similarly, when these embryos were subjected to pro-apoptotic genes (BAX, BAD, BAK), expression was found to be slightly higher in blastocysts than other stages. This study shows that calcium ionophore-activated blastocysts were developmentally more competent than the ethanol-activated blastocysts.

Malignant hyperthermia in a 6-month-old infant.

Malignant hyperthermia (MH) is a rare hypermetabolic disorder of skeletal muscles that manifests as a life-threatening crisis in susceptible individuals, after exposure to triggering agents, most commonly halothane and succinylcholine. MH presents with multiple nonspecific signs and laboratory findings such as tachycardia, hyperthermia, hypercarbia, acidosis, and muscle rigidity. Caffeine halothane contracture test is not available at most centers in India. Larach et al. have described a clinical grading scale for determining the MH raw score based on clinical findings and biochemical tests. The high degree of suspicion, early recognition and aggressive treatment should commence immediately. It is imperative to avoid triggering agents, such as volatile anesthetics and succinylcholine, and promote the use of total intravenous anesthesia in MH susceptible patients. We report a case of 6-month-old child undergoing laparotomy under general anesthesia, who presented with signs and symptoms of MH, had MH rank 5 and raw score 36.

Human immunodeficiency virus, hepatitis B virus and hepatitis C virus seroprevalence in critically ill emergency department patients at a Trauma Care Centre, India.

INTRODUCTION: Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are the most common occupationally acquired infections amongst the healthcare workers (HCWs) with critically ill patients attending the emergency department being the most common source of occupationally acquired infections. Therefore, the present study was conducted at a 165 bedded level-1 trauma centre of India to ascertain the seroprevalence rate of HIV, HBV and HCV; and thus the risk associated with the occupational exposure in a busy emergency setting of the developing world. METHODOLOGY: A retrospective, 7 years study (2007-2013) was carried out at the JPNA Trauma Centre of the 2,500 bedded All India Institute of Medical Sciences, New Delhi. Records of all patients whose serum samples were sent to the laboratory for viral markers testing were obtained and those falling in the red area were included. RESULTS: A total of 11,630 patients were received in the red area; and samples from 7,650 patients were sent for testing. Seropositivity of HIV, HBV and HCV in these samples was 0.28%, 3.4% and 0.9% respectively. The number of samples received was lesser than the total number of patients received in the red area. CONCLUSION: Adopting Standard Precautions (SP) can be used as an easy method to decrease the risk of occupationally acquired infections.

Single versus double blade technique for skin incision and deep dissection in surgery for closed fracture: a prospective randomised control study.

PURPOSE: To compare blade cultures in surgery for closed fracture using a single or double blade technique to determine whether the current practice of double blade technique is justified. METHODS: 155 men and 29 women aged 20 to 60 (mean, 35) years who underwent surgery for closed fracture with healthy skin at the incision site were included. Patients were block randomised to the single (n=92) or double (n=92) blade technique. Blades were sent for bacteriological analysis. Outcome measures were early surgical site infection (SSI) within 30 days and cultures from the blades. RESULTS: The 2 groups were comparable in baseline characteristics. In the single blade group, 6 surgical blades and 2 control blades showed positive cultures; 4 patients developed SSI, but only one had a positive culture from the surgical blade (with different organism isolated from the wound culture). In the double blade group, 6 skin blades, 7 deep blades, and 0 control blade showed positive culture; only 2 patients had the same bacteria grown from both skin and deep blade. Five patients developed SSI, but only one patient had a positive culture from the deep blade (with different organism isolated from the wound culture). The difference in incidence of culture-positive blade or SSI between the 2 groups was not significant. The relative risk of SSI in the single blade group was 0.8. Positive blade culture was not associated with SSI in the single or double blade group. CONCLUSION: The practice of changing blade following skin incision has no effect on reducing early SSI in surgery for closed fracture in healthy patients with healthy skin.

Leptospirosis among the self-supporting convicts of Andaman Island during the 1920s--the first report on pulmonary haemorrhage in leptospirosis?

Several researchers had carried out investigations on the possibility of existence of Weil's disease in Andaman Islands during early 20 th century. The first report of a series of confirmed cases of leptospirosis that occurred during 1929 was published in 1931.There were several reports during 1995 to 2009 that described detailed account of leptospirosis including various clinical syndromes. The possibility of pulmonary involvement in leptospirosis being a manifestation historically overlooked rather than newly emerged during the past two decades is examined in this review in the context of Andaman Islands. Two case series of leptospirosis, one occurred in 1929 and the other in 1996-1997 were reviewed with special emphasis on pulmonary involvement and haemorrhagic manifestations. The similarities and differences in the clinical profile of patients of the two case series were analysed. The review shows that respiratory system involvement and pulmonary haemorrhage as evidenced by presence of haemoptysis as a complication of leptospirosis was occurring during 1920s in Andaman Islands. The incidence of pulmonary involvement, however, rose from 9.4 per cent during 1929 to 52 per cent in 1996-1997. The case fatality ratio in patients with pulmonary involvement, which was 50 per cent during 1929 and 42.9 per cent during 1996-1997, was higher than that in cases without pulmonary involvement.Fever, conjunctival congestion, jaundice, vomiting, diarrhoea, hepatomagaly, haemoptysis, haematemesis and subconjunctival haemorrhage were common in both series. The case series in Andaman Islands in 1929 was probably the first report of pulmonary haemorrhage as a manifestation of leptospirosis. The increase in the incidence of pulmonary involvement in leptospirosis in the recent past is probably due to the increase in the density and diversity of its animal vectors,the broadening of the range of circulating serovars and the interactions between the vector and the agent. An increased virulence of Leptospira through gene acquisition and loss on an evolutionary time scale and the resulting change in the gene content, gene order and gene expression cannot be ruled out.

Outcomes of surgical site infections in orthopedic trauma surgeries in a tertiary care centre in India.

BACKGROUND: Surgical site infections (SSIs) still cause significant morbidity and mortality despite advances in trauma care. We have studied in this paper the rate of SSIs, their outcomes in patients undergoing interventions for trauma and SSI trends in developing countries. MATERIALS AND METHODS: A 16-month study (May, 2011- August, 2012) was carried out. Patients undergoing interventions for orthopedic trauma were followed and assessed for SSIs and their outcomes and antimicrobial sensitivity patterns of the micro-organisms isolated were noted and correlated. RESULTS: A total of 40 (4.4%) confirmed cases of SSIs were identified among 852 patients of orthopedic trauma. Based on the new CDC criteria, after ruling out cellulitis, only 24 (2.6%) were found to have SSIs. A total of 12.5% of the SSIs were detected during follow-up. Acinetobacter baumannii was the predominant organism as also Staphylococcus aureus. Outcomes observed included changes in antibiotic regime, revision surgery, readmission to hospital and deaths. CONCLUSION: SSI is prevalent in orthopaedic trauma patients and an active surveillance program will help in early management and prevention.

Identification of protein succination as a novel modification of tubulin.

Protein succination is a stable post-translational modification that occurs when fumarate reacts with cysteine residues to generate 2SC [S-(2-succino)cysteine]. We demonstrate that both α- and ß-tubulin are increasingly modified by succination in 3T3-L1 adipocytes and in the adipose tissue of db/db mice. Incubation of purified tubulin from porcine brain with fumarate (50 mM) or the pharmacological compound DMF (dimethylfumarate, 500 µM) inhibited polymerization up to 35% and 59% respectively. Using MS we identified Cys347α, Cys376α, Cys12ß and Cys303ß as sites of succination in porcine brain tubulin and the relative abundance of succination at these cysteine residues increased in association with fumarate concentration. The increase in succination after incubation with fumarate altered tubulin recognition by an anti-α-tubulin antibody. Succinated tubulin in adipocytes cultured in high glucose compared with normal glucose also had reduced reactivity with the anti-α-tubulin antibody; suggesting that succination may interfere with tubulin-protein interactions. DMF reacted rapidly with 11 of the 20 cysteine residues in the αß-tubulin dimer, decreased the number of free thiols and inhibited the proliferation of 3T3-L1 fibroblasts. Our data suggest that inhibition of tubulin polymerization is an important undocumented mechanism of action of DMF. Taken together, our results demonstrate that succination is a novel post-translational modification of tubulin and suggest that extensive modification by fumarate, either physiologically or pharmacologically, may alter microtubule dynamics.

Decision-making in Colorectal Cancer Tumor Board meetings: results of a prospective observational assessment.

BACKGROUND: The management of colorectal cancer increasingly involves multidisciplinary tumor boards. In cases where these occur, the quality can be variable. Despite this, there are no uniform measures to evaluate them. The aim of this study was to evaluate the performance of colorectal cancer tumor boards, via real-time prospective observation. METHODS: An observational tool, termed Colorectal Multidisciplinary Team Metric for Observation of Decision-Making (cMDT-MODe), was used to assess decision-making in 267 cases. The presentation of case history, radiological and pathological information, as well as contributions to decision making of the various team members were analyzed using descriptive statistics and t-tests. Interobserver agreement was assessed using intraclasscorrelation coefficients. RESULTS: Tumor board meetings lasted 76 min, were attended by approximately 16 specialists each, and reviewed an average of 24 cancer cases (3 min per case review). Regarding the quality of presented information to the team, case history information was rated the highest (mean 4.57), followed by radiological information (mean 4.22) and pathological information (mean 3.81). Regarding each team-member's contribution to discussion, surgeons were scored the highest (mean 4.81), followed by radiologists (mean 4.41) and meeting chairs (mean 4.13)--all team members except the board coordinators were scored highly. Overall scoring reliability was good (0.79). CONCLUSIONS: The cMDT-MODe instrument can be reliably used to prospectively assess decision making in the multidisciplinary management of colorectal patients. By systematically quantifying the quality of a colorectal cancer tumor board, we can identify areas for improving practice so as to optimize decision making for cancer care.

Beta-hemolytic streptococcal infections in trauma patients.

PURPOSE: ß-hemolytic streptococci (ßHS) causes a diverse array of human infections. The molecular epidemiology of ß-hemolytic streptococcal infections in trauma patients has not been studied. This study reports the molecular and clinical epidemiology of ß-hemolytic streptococcal infections at a level 1 trauma centre of India. METHODS: A total of 117 isolates of ßHS were recovered from clinical samples of trauma patients. The isolates were identified to species level and subjected to antimicrobial susceptibility testing. Polymerase chain reaction (PCR) assay was done to detect exotoxin virulence genes. The M protein gene (emm gene) types of GAS strains were ascertained by sequencing. RESULTS: Group A Streptococcus (GAS) was the most common isolate (64 %), followed by group G Streptococcus (23 %). A large proportion of GAS produced speB (99 %), smeZ (91 %), speF (95 %) and speG (87 %). smeZ was produced by 22 % of GGS. A total of 25 different emm types/subtypes were seen in GAS, with emm 11 being the most common. Resistance to tetracycline (69 %) and erythromycin (33 %) was commonly seen in GAS. CONCLUSIONS: ß-hemolytic streptococcal infections in Indian trauma patients are caused by GAS and non-GAS strains alike. A high diversity of emm types was seen in GAS isolates, with high macrolide and tetracycline resistance. SpeA was less commonly seen in Indian GAS isolates. There was no association between disease severity and exotoxin gene production.

A case of dual infection in a paediatric trauma victim of primary cutaneous aspergillosis caused by Aspergillus flavus and Aspergillus terreus.

Aspergillus spp. are widely distributed throughout the environment. They are opportunistic pathogens causing infection at various sites in the body such as lungs, sinuses, eyes, skin, central nervous system etc., Primary cutaneous aspergillosis is an uncommon disease entity. Primary infections usually occur at sites having disruption of the skin and usually occur in burn patients, trauma and surgical patients. A 4-year-old girl who was run over by a truck and suffered extensive de-gloving injury to bilateral lower limbs developed greenish discharge and scaly lesions around the wound margins after 50 days of hospital stay. The skin biopsy demonstrated the presence of thin septate hyphae branching at acute angles and culture demonstrated growth of Aspergillus flavus and Aspergillus terreus. The child was started on voriconazole therapy for 3 weeks and the lesion healed satisfactorily. Subsequent skin biopsy culture was negative for fungi. Prompt diagnosis and management of such cases can salvage the limbs in severe trauma cases.

Kolaviron prevents carbendazim-induced steroidogenic dysfunction and apoptosis in testes of rats.

The study evaluated the protective role of kolaviron (an isolated biflavonoid from the seed of Garcinia kola) and vitamin E in carbendazim-induced reproductive dysfunction in male rats. Adult male Wistar rats were orally exposed to carbendazim (200mg/kg) singly or in combination with kolaviron (100 and 200mg/kg). Exposure to carbendazim significantly decreased the activities of superoxide dismutase and catalase but markedly increased sialic acid concentration and lipid peroxidation in the testes of rats. Western blot analysis revealed that carbendazim treatment decreased the expression of steroid acute regulatory (StAR) protein and androgen binding protein (ABP) with concomitant decrease in activities of steroidogenic enzymes. Germ cell apoptosis in carbendazim-treated rats was confirmed by TUNEL assay. However, pretreatment with kolaviron and vitamin E restored the testicular antioxidant status and steroidogenesis and decreased apoptotic nuclei to near control level in carbendazim-treated rats. Kolaviron may prove useful in combating carbendazim-induced reproductive toxicity.

Nonylphenol induces apoptosis via mitochondria- and Fas-L-mediated pathways in the liver of adult male rat.

Nonylphenol (NP) is an environmental contaminant known to possess estrogenic properties. Humans are constantly exposed to NP by contaminated water and food products. In the present study we sought to investigate whether treatment with low doses of NP induces apoptosis in the liver of adult rats. Rats were administered with NP by oral gavage at the doses of 15,150 and 1500 µg/kg body weight per day for 45 days. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assayed. Apoptosis-related proteins namely cytochrome c, caspase-3, caspase-8, caspase-9, Fas and Fas-l, and expression of bcl-2 mRNA and bax mRNA were examined in the liver. Levels of AST and ALT were increased in the treated rats. Western blot analysis revealed elevation in the levels of cytochrome c, caspase-3, caspase-8, caspase-9, Fas and Fas-l in the liver of NP-treated rats. Decreased expression of bcl-2 mRNA (anti-apoptotic) and increased expression of bax mRNA (apoptotic) were observed in the liver of treated rats. Increased localization of caspase-3 in the hepatocytes and DNA damage were observed in the liver of treated rat. It is concluded that NP induces apoptosis in liver involving both mitochondria-dependent and Fas-Fas-l pathways and thereby, leading to hepatic damage in rats.

Inter-laboratory comparison of methods to measure androstenone in pork fat.

Today, different analytical methods are used by different laboratories to quantify androstenone in fat tissue. This study shows the comparison of methods used routinely in different laboratories for androstenone quantification: Time-resolved fluoroimmunoassay in Norwegian School of Veterinary Science (NSVS; Norway), gas chromatography coupled to mass spectrometry in Co-operative Central Laboratory (CCL; The Netherlands) and in Institut de Recerca i Tecnologia Agroalimentàries (IRTA; Spain), and high-pressure liquid chromatography in Agroscope Liebefeld-Posieux Research Station (ALP; Switzerland). In a first trial, a set of adipose tissue (AT) samples from 53 entire males was sent to CCL, IRTA and NSVS for determination of androstenone concentration. The average androstenone concentration (s.d.) was 2.47 (2.10) µg/g at NSVS, 1.31 (0.98) µg/g at CCL and 0.62 (0.52) µg/g at IRTA. Despite the large differences in absolute values, inter-laboratory correlations were high, ranging from 0.82 to 0.92. A closer look showed differences in the preparation step. Indeed, different matrices were used for the analysis: pure fat at NSVS, melted fat at CCL and AT at IRTA. A second trial was organised in order to circumvent the differences in sample preparation. Back fat samples from 10 entire males were lyophilised at the ALP labortary in Switzerland and were sent to the other laboratories for androstenone concentration measurement. The average concentration (s.d.) of androstenone in the freeze-dried AT samples was 0.87 (0.52), 1.03 (0.55), 0.84 (0.46) and 0.99 (0.67) µg/g at NSVS, CCL, IRTA and ALP, respectively, and the pairwise correlations between laboratories ranged from 0.92 to 0.97. Thus, this study shows the influence of the different sample preparation protocols, leading to major differences in the results, although still allowing high inter-laboratory correlations. The results further highlight the need for method standardisation and inter-laboratory ring tests for the determination of androstenone. This standardisation is especially relevant when deriving thresholds of consumer acceptance, whereas the ranking of animals for breeding purposes will be less affected due to the high correlations between methods.