Contribution of infection and vaccination to population-level seroprevalence through two COVID waves in Tamil Nadu, India.

This study employs repeated, large panels of serological surveys to document rapid and substantial waning of SARS-CoV-2 antibodies at the population level and to calculate the extent to which infection and vaccination separately contribute to seroprevalence estimates. Four rounds of serological surveys were conducted, spanning two COVID waves (October 2020 and April-May 2021), in Tamil Nadu (population 72 million) state in India. Each round included representative populations in each district of the state, totaling ≥ 20,000 persons per round. State-level seroprevalence was 31.5% in round 1 (October-November 2020), after India's first COVID wave. Seroprevalence fell to 22.9% in round 2 (April 2021), a roughly one-third decline in 6 months, consistent with dramatic waning of SARS-Cov-2 antibodies from natural infection. Seroprevalence rose to 67.1% by round 3 (June-July 2021), with infections from the Delta-variant induced second COVID wave accounting for 74% of the increase. Seroprevalence rose to 93.1% by round 4 (December 2021-January 2022), with vaccinations accounting for 63% of the increase. Antibodies also appear to wane after vaccination. Seroprevalence in urban areas was higher than in rural areas, but the gap shrunk over time (35.7 v. 25.7% in round 1, 89.8% v. 91.4% in round 4) as the epidemic spread even in low-density rural areas.

Assessment of Registry-Based Surveillance Statistics Used for Cancer Control in the Dindigul District in South India.

Background: Cancer incidence rates from the Dindigul district were lower by 50% than Chennai in Tamil Nadu for most cancers. This study describes the cancer surveillance statistics and provides an assessment of missing cases from routine registration in the Dindigul Ambilikkai Cancer Registry (DACR), covering a predominantly rural population in the Dindigul district. Method: A total of 21,214 incident cancers in the DACR during 2003-2017 were examined for this study. Cancer registration was carried out by active case-finding following standard international norms. A total of 12,541 incident cancers registered during 2003-2012 and followed through 2014 were used to estimate survival. Data on follow-up were obtained through a mixture of active and passive methods. Survival probability was estimated by actuarial methods. A random survey carried out independently was used to assess the quality of case ascertainment. Results: The age-standardized rate (ASR) per 100,000 population was higher among women (76.2) than men (61) in 2013-2017, with both sexes reporting a 17% increase compared to 2003-2007. The most common cancers were cervix (ASR,18.5) and female breast (ASR,17.1), with percentage changes of -19% and +46.1%, respectively. Lung cancer (ASR, 5.5) was top among men with an increasing trend (+57.1%). The percent change in ASR of mouth cancer showed opposite trends among men (+24.3%) and women (- 21.4%). The ASR of colorectal cancers almost doubled among men between 2003-2007 and 2013-2017 (3.9; +94.7%). The 5- and 10-year absolute survival for all cancers were 31% and 20%, respectively. Out of 365 incident cancers that occurred during 2003-2010 in the surveyed areas, 310 (84.9%) were already registered in the DACR, while 55 were newly identified from the survey (15.1%). Inadequate coverage of sources outside the Dindigul district was significant (P = .002), with the highest number of missed cases from hospitals under nongovernment sectors (58.3%). Underascertainment was higher among cancer patients living in hilly regions (60%) and border areas (47.4%) than in core regions (P = .05). Conclusion: Because of an enacted government order making cancer a notifiable disease, the registry-based cancer surveillance could be extended, covering a population of 80 million in a cost-effective manner with enhanced coverage and systematic evaluation of cancer-screening programs.

Household catastrophic health expenditure for COVID-19 during March-August 2021, in South India: a cross-sectional study.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic increased the utilisation of healthcare services. Such utilization could lead to higher out-of-pocket expenditure (OOPE) and catastrophic health expenditures (CHE). We estimated OOPE and the proportion of households that experienced CHE by conducting a cross-sectional survey of 1200 randomly selected confirmed COVID-19 cases. METHODS: A cross-sectional survey was conducted by telephonic interviews of 1200 randomly selected COVID-19 patients who tested positive between 1 March and 31 August 2021. We collected household-level information on demographics, income, expenditure, insurance coverage, direct medical and non-medical costs incurred toward COVID-19 management. We estimated the proportion of CHE with a 95% confidence interval. We examined the association of household characteristics; COVID-19 cases, severity, and hospitalisation status with CHE. A multivariable logistic regression analysis was conducted to ascertain the effects of variables of interest on the likelihood that households face CHE due to COVID-19. RESULTS: The mean (95%CI) OOPE per household was INR 122,221 (92,744-1,51,698) [US$1,643 (1,247-2,040)]. Among households, 61.7% faced OOPE, and 25.8% experienced CHE due to COVID-19. The odds of facing CHE were high among the households; with a family member over 65 years [OR = 2.89 (2.03-4.12)], with a comorbid individual [OR = 3.38 (2.41-4.75)], in the lowest income quintile [OR = 1.82 (1.12-2.95)], any member visited private hospital [OR = 11.85 (7.68-18.27)]. The odds of having CHE in a household who have received insurance claims [OR = 5.8 (2.81- 11.97)] were high. Households with one and more than one severe COVID-19 increased the risk of CHE by more than two-times and three-times respectively [AOR = 2.67 (1.27-5.58); AOR = 3.18 (1.49-6.81)]. CONCLUSION: COVID-19 severity increases household OOPE and CHE. Strengthening the public healthcare and health insurance with higher health financing is indispensable for financial risk protection of households with severe COVID-19 from CHE.

Role of Covid vaccine in determining ICU admission and death due to Covid -19 in Tamil Nadu

COVID-19 pandemic threatened the world in terms of its rapid spread, strain on health infrastructure and many people lost their lives due to COVID. Mass Vaccination of public against Covid-19 were done with the notion that it protects against the severe form of the disease and death due to Covid-19. Covid vaccination was rolled out in Tamil Nadu from 16th January 2021 in a phased manner. This study was done using secondary data to assess the role of COVID vaccination in preventing ICU admission and death due to Covid-19 in Tamil Nadu for the period of August - December 2021. Unvaccinated individuals contributed to a higher proportion of hospitalization (60.9%) and ICU admission (65.5%) among Covid-19 infected during this period. Similarly, among patients who died due to Covid-19, 75.5% were unvaccinated. Odds of ICU admission and death among unvaccinated was 2.01 and 3.19 - times higher compared to fully vaccinated individuals infected with Covid-19. Unvaccinated Covid-19 patients had 2.73- and 1.46- times increased odds of dying and ICU admission respectively, compared to partially vaccinated. Population Attributable Risk showed that receiving at least one dose of vaccine could have reduced the mortality among Covid patients by 54% and ICU admission by 23.3%. This article emphasizes the need for vaccination against Covid-19 to reduce ICU admission and death among those infected with Covid-19.

S Gene Target Failure (SGTF) in Commercial Multiplex RT-PCR assay as indicator to detect SARS-CoV-2 VOC B.1.1.7 lineage in Tamil Nadu, India

Emergence of Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) Variants of Concern (VOC) possessing improved virulence, transmissibility and/or immune-escape capabilities has raised significant public health concerns. In order to identify VOCs, WHO recommends Whole-Genome Sequencing approach, which is costly and involves longer completion time. Hence, potential role of commercial multiplex RT-PCR kit to screen variants rapidly is being attempted in this study. A total of 1200 suspected COVID samples from different districts of Tamil Nadu State (India) were screened with Thermo TaqPath RT-PCR kit and Altonas Realstar RT-PCR Assay kit. Among 1200 screened, S-gene target failure (SGTF) phenomenon were identified in 112 samples while testing with TaqPath RT-PCR Kit. 100% concordant results were observed between SGTF phenomenon and whole-genome sequencing (WGS) results in detecting SARS-CoV-2 VOC B.1.1.7. TaqPath RT-PCR assay testing can be utilized by laboratories to screen rapidly the VOC B.1.1.7 variants, thus enabling early detection of B.1.1.7 variant infection and transmission in population. This in turn will pave way to implement suitable preventive measures by appropriate authorities to control the transmission of the viral variant.

Seroprevalence in Tamil Nadu through India's two COVID waves: Evidence on antibody decline following infection and vaccination

Four rounds of serological surveys were conducted, spanning two COVID waves (October 2020 and April-May 2021), in Tamil Nadu (population 72 million) state in India. Each round included representative populations in each district of the state, totaling [≥]20,000 persons per round. State-level seroprevalence was 31.5% in round 1 (October-November 2020), after Indias first COVID wave. Seroprevalence fell to 22.9% in 2 (April 2021), consistent with waning of antibodies from natural infection. Seroprevalence rose to 67.1% by round 3 (June-July 2021), reflecting infections from the Delta-variant induced second COVID wave. Seroprevalence rose to 93.1% by round 4 (December 2021-January 2022), reflecting higher vaccination rates. Antibodies also appear to wane after vaccination. Seroprevalence in urban areas was higher than in rural areas, but the gap shrunk over time (35.7 v. 25.7% in round 1, 89.8% v. 91.4% in round 4) as the epidemic spread even in low-density rural areas. Article Summary LineAntibodies waned after Indias first COVID wave and both vaccination and infection contributed its roughly 90% seroprevalence after its second wave.

Differential responses of sorghum genotypes to drought stress revealed by physio-chemical and transcriptional analysis.

Sorghum is an essential food crop for millions of people in the semi-arid regions of the world, where its production is severely limited by drought stress. Drought in the early stages of crop growth and development irreversibly interferes, which leads to poor yield. The effect of drought stress in sorghum was studied at physiological, biochemical, and molecular levels in a set of two genotypes differing in their tolerance to drought. Drought stress was imposed by restraining water for 10 days on 25 days old seedlings. A significant influence of water stress was observed on the considered morpho-physiological and biochemical traits. The genotype DRT1019 exhibited physiological and biochemical indicators of drought avoidance through delayed leaf rolling, osmotic adjustment, ideal gas-exchange system, solute accumulation, an increased level of enzyme synthesis and root trait expression as compared to the ICSV95022 genotype. Furthermore, differences in the metabolite changes viz. total carbohydrate, total amides, and lipids were found between the two genotypes under drought stress. In addition, transcript profiling of potential candidate drought genes such as SbTIP3-1, SbDHN1, SbTPS, and SbDREB1A revealed up-regulation in DRT1019, which corresponded with other important physiological and biochemical parameters exhibited in the genotype. In conclusion, this study provides an improved understanding of whole plant response to drought stress in sorghum. Additionally, our results provide promising candidate genes for drought tolerance in sorghum that can be used as potential markers for drought tolerance breeding programs.

Jarcho's Syndrome: Bone Marrow Infiltrates from a Gastric Malignancy.

Bone and bone marrow metastasis is extremely rare in adenocarcinoma particularly from the stomach. We present a case of gastric carcinoma primarily manifesting as anemia and pancytopenia. On evaluation, he was found to have bone marrow secondaries from a gastric primary tumor. Though such metastasis is rare, patients with refractory anemia must be evaluated to search for solid organ malignancy like the stomach.

Chimeric antigen receptors for treatment of glioblastoma: a practical review of challenges and ways to overcome them.

Glioblastoma (GBM) is by far the most common and the most aggressive of all the primary brain malignancies. No curative therapy exists, and median life expectancy hovers at around 1 year after diagnosis, with a minute fraction surviving beyond 5 years. The difficulty in treating GBM lies in the cancer's protected niche within the blood-brain barrier and the heterogeneity of the cancer cells, which possess varying degrees of susceptibility to various common modalities of treatment. Over time, it is the tumor heterogeneity of GBM and the ability of the cancer stem cells to evolve in response treatment that renders the cancer refractory to conventional treatment. Therefore, research has increasingly focused on treatment that incorporates knowledge of GBM molecular biology to therapeutic strategies. One type of therapy that shows great promise is the area of T-cell immunotherapy to target GBM-specific tumor antigens. One attractive strategy is to use T cells that have undergone genetic modification to express a chimeric antigen receptor capable of interacting with tumor antigens. In this article, we will review chimeric antigen receptor T-cell therapy, their advantages, drawbacks, challenges facing their use and how those challenges may be overcome.

Manipulating the expression of chemokine receptors enhances delivery and activity of cytokine-induced killer cells.

BACKGROUND: Cytokine-induced killer (CIK) cells are ex vivo-expanded immune cells that express NK-cell and T-cell markers and that are routinely used in the treatment of many cancers. One key advantage of CIK cells is their ability to efficiently traffic to many solid tumours. Although likely to be mediated by chemokine receptor (CKR) expression, a thorough examination of the mechanism of tumour targeting has not been previously explored. METHODS: Here, human CIK cell expansions were examined for the level, profile and kinetics of CKR expression. RESULTS: It was found that CIK cells express a panel of CKRs, with considerable variation between donors. Importantly, CKR levels dropped considerably beyond 14 days in culture, being significantly reduced by day 28 (the time at which cytolytic activity peaked). As such, CIK preparations that are used clinically may not have optimal CKR expression. Several approaches were found to re-stimulate CKR cell-surface levels at these later time points. These approaches also enhanced cytolytic activity in vitro and were demonstrated to increase both in vivo tumour trafficking and anti-tumour activity in mouse models. CONCLUSIONS: Simple modifications of the CIK expansion protocol could therefore be used to significantly enhance the anti-tumour effects of this therapy.

Potential for enhanced therapeutic activity of biological cancer therapies with doxycycline combination.

Despite significant strides made in the clinical translation of adoptive immune cell therapies, it is apparent that many tumors incorporate strategies to avoid recognition by receptors expressed on the immune cells, such as NKG2D. Strategies that stabilize the expression of ligands for these receptors may enhance the therapeutic potential of these and related therapies. Doxycycline inhibits matrix metalloproteinases (MMPs) that act to cleave the extracellular domain of MICA/B, ligands for the NKG2D receptor. Doxycycline treatment blocked shedding of MICA/B from a panel of human tumor cells, but also acted to increase their expression and cell surface translocation, possibly through its action on ATM. This meant that many tumor cells displayed increased MICA/B expression and enhanced susceptibility to CIK cells. Interestingly, doxycycline also selectively enhanced the replication of oncolytic vaccinia in many tumor cell lines, leading to increased sensitivity to these therapies. Combination (CIK-oncolytic vaccinia) therapies used in conjunction with doxycycline led to increased anti-tumor effects. The unexpected and pleiotropic beneficial anti-tumor effects of doxycycline on both immune cell and oncolytic viral therapies make it an excellent candidate for rapid clinical testing.

Cancer pattern and survival in a rural district in South India.

BACKGROUND: Cancer pattern data are rare and survival data are none from rural districts of India. METHODS: The Dindigul Ambilikkai Cancer Registry (DACR) covering rural population of 2 millions in Dindigul district, Tamil Nadu state, South India, registered 4516 incident cancers during 2003-2006 by active case finding from 102 data sources for studying incidence pattern, of which, 1045 incident cancers registered in 2003 were followed up for estimating survival. House visits were undertaken annually for each registered case for data completion. Cancer pattern was described using average annual incidence rates and survival experience was expressed by computing observed survival by actuarial method and age-standardized relative survival (ASRS). RESULTS: The average annual age-standardized rate per 100,000 of all cancers together was higher among women (62.6) than men (51.9) in DACR. The most common cancers among men were stomach (5.6), mouth (4.2) and esophagus (3.7). Cervical cancer (22.1) was ranked at the top among women followed by breast (10.9) and ovary (3.3). DACR incidence rates were lesser by at least two folds and 5-year survival were on par or lower than Chennai metropolitan registry for most cancers. Five-year age-standardized relative survival (%) in DACR was as follows: all cancers (29%), larynx (48), mouth (42), breast/tongue (38) and cervix (37). CONCLUSION: Cancer incidence was significantly lower, cancer patterns were markedly different and population-based cancer survival was lower in rural areas than urban areas thus providing valuable leads in estimating realistic cancer burden and instituting cancer control programs in India.

Role of lipid-soluble complexes in targeted tumor therapy.

UNLABELLED: Radionuclide therapy remains a promising arsenal against cancer. However, low tumor uptake, high radiation dose to normal organs, and subsequent adverse effects are challenging problems. This study assessed the therapeutic significance of lipid-soluble compounds of (111)In, which passively diffuse through the cell membrane, bind to cytoplasmic components, and remain cell bound until decay. METHODS: Athymic nude mice bearing human colorectal, prostate, or breast cancer received 11.1-14.8 MBq (300-400 micro Ci) (111)In-8-hydroxyquinoline ((111)In-oxine) or (111)In-mercaptopyridine-N-oxide ((111)In-Merc) in 200 micro L solution intratumorally through a multihole needle. Tumors in some mice were dissected, and 20- micro m-thick sections were autoradiographed. In additional mice, tumor diameter was measured daily, mice were imaged and weighed, and blood samples were drawn for determination of neutrophil counts for up to 28 d after injection. Some mice were sacrificed at predetermined times for quantitative tissue distribution of (111)In. Additionally, tumor cells were labeled with (111)In-oxine and homogenized, and (111)In associated with cell components was determined using polyacrylamide gel electrophoresis. Radiation dose that could be delivered to adjacent tissues was estimated. The (111)In absorbed dose as a function of radial position r in a 1-g tumor was theoretically compared with those of beta-emitting radionuclides (90)Y and (177)Lu. RESULTS: More than 85% of (111)In remained in tumors, bound to cell cytoplasmic components of apparent molecular weights 250 and 6 kDa. (111)In in tumors was uniformly distributed. Only 2% of the injected (111)In was in the liver, kidneys, and carcass. Statistical analysis showed that on day 28, control tumors grew >100%, whereas treated tumors either had growth arrest or grew only slowly (17%). The estimated radiation dose per megabecquerel (millicurie) injected was 90 Gy/g (9,000 rad/g), of which 64% was from conversion electrons, 16% from Auger electrons, 20% from gamma-photons and x-rays, respectively. Radiation dose to adjacent normal organs was 5%-10% of the radiation dose to the tumor and negligible to the liver and kidneys. Neutrophil counts remained unchanged. Mouse body weight was +/-10% of the initial weight. The radiation dosimetry for (111)In and (177)Lu compared favorably, but not that of (90)Y. CONCLUSION: Treatment is independent of receptor density, heterogeneity, or the hypoxic status of cells. It is applicable to treat all known and accessible tumor types, and it delivers a negligible radiation dose to vital organs and only 5%-10% of the radiation dose to organs adjacent to the tumor. Intratumoral administration of (111)In-oxine appears to be a feasible, effective, safe, and promising treatment for cancer.

Combined anterior craniofacial resection for tumors involving the cribriform plate: early postoperative complications and technical considerations.

OBJECTIVE: Combined craniofacial resection has become the standard approach for malignant tumors involving the cribriform plate and anterior cranial fossa. Despite its widespread application, however, many surgeons agree that the procedure carries a risk of significant morbidity and even mortality. The purpose of this study was to analyze the experience at a single institution to determine the incidence of early postoperative complications encountered after combined craniofacial resection of tumors involving the cribriform plate and to provide information to improve management. METHODS: Between 1987 and 1997, 168 patients underwent combined craniofacial resection at the National Cancer Institute of Milan for tumors involving the cribriform plate. Patient charts, operative notes, follow-up clinic notes, radiographic studies, and pathology reports were analyzed. Morbidity encountered in the first 30 cases was compared with that encountered in the subsequent 138 cases. RESULTS: The most frequently encountered pathological findings were adenocarcinoma (53.6%), squamous cell carcinoma (17%), and esthesioneuroblastoma (9.8%). Eight patients (4.7%) died, 6 of whom were among the first 30 patients to undergo resection. Among patients with fatal complications were three with meningoencephalitis, three with intracranial hemorrhage, and one with myocardial infarction. Fifty patients (29.7%) had nonfatal morbidity; 16 of these patients were among the first 30 patients operated. Transient cerebrospinal fluid leakage was the most frequent adverse effect (9.5%); 12 patients (7.1%) had pneumocephalus, 3 (1.8%) had meningitis, 4 (2.4%) had wound infections, 3 (1.8%) experienced transient impairment of mental status, 3 (1.8%) had transient diplopia, 2 (1.2%) had diabetes insipidus, and 1 (0.6%) had bone flap necrosis. CONCLUSION: We observed a dramatic decrease in mortality and morbidity in patients who underwent combined craniofacial resection after the first 30 cases in our series. Improvement of specific aspects of surgical technique, such as more refined reconstructive methods and improved prophylactic antibiotic therapy, is at least partly responsible for this favorable trend.

O6-benzylguanine potentiates the antitumor effect of locally delivered carmustine against an intracranial rat glioma.

Local delivery of carmustine (BCNU) via biodegradable polymers prolongs survival against experimental brain tumors and in human clinical trials. O6-benzylguanine (O6-BG), a potent inhibitor of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT), has been shown to reduce nitrosourea resistance and, thus, enhance the efficacy of systemic BCNU therapy in a variety of tumor models. In this report, we demonstrate that O6-BG can potentiate the activity of BCNU delivered intracranially via polymers in rats challenged with a lethal brain tumor. Fischer 344 rats received a lethal intracranial challenge of 100,000 F98 glioma cells (F98 cells have significant AGT activity, 328 fmol/mg protein). Five days later, animals receiving an i.p. injection of O6-BG (50 mg/kg) 2 h prior to BCNU polymer (3.8% BCNU by weight) implantation had significantly improved survival (n = 7; median survival, 34 days) over animals receiving either O6-BG alone (n = 7; median survival, 22 days; P = 0.0002) or BCNU polymer alone (n = 8; median survival, 25 days; P = 0.0001). Median survival for the control group (n = 8) was 23.5 days. Moreover, there was no physical, behavioral, or pathological evidence of treatment-related toxicity. These findings suggest that O6-BG can potentiate the effects of interstitially delivered BCNU and, for tumors expressing significant AGT, may be necessary for the BCNU to provide a meaningful therapeutic benefit. Given the clinical use of BCNU polymers against malignant gliomas, concurrent treatment with O6-BG may provide an important addition to our therapeutic armamentarium.

Cognitive impairments after surgical repair of ruptured and unruptured aneurysms.

OBJECTIVES: To determine the frequency and severity of neuropsychological impairments associated with aneurysmal subarachnoid haemorrhage, and associated with repair of intracerebral aneurysms. METHODS: Two groups of patients who underwent repair of intracerebral aneurysms were studied: patients with unruptured aneurysms (n=20) and patients with ruptured aneurysms (n=27). All patients were administered a battery of standardised neuropsychological tests about 3 months after surgery. A subset of 12 patients with unruptured aneurysms were administered the battery both before and after elective repair of the aneurysm(s). A subset of six patients with ruptured aneurysms were given the test at both 3 months and 1 year after surgery. RESULTS: As previously reported for patients with ruptured aneurysms, patients with both ruptured and unruptured aneurysms performed, as a group, significantly below published norms on many of the neuropsychological tests after surgery. However, there were significant differences between preoperative and postoperative performance in the unruptured aneurysm group only on a few tests: measures of word fluency, verbal recall, and frontal lobe function. Performance of patients with ruptured aneurysms was significantly below that of patients with unruptured aneurysms only on a few tests of verbal and visual memory. In addition, group differences compared with published norms reflected severely impaired performance by a minority of patients, rather than moderately impaired performance in a majority of patients. CONCLUSIONS: Although patients who undergo repair of ruptured aneurysms perform, as a group, below published norms on many neuropsychological tests, significant impairments are seen in a minority of patients. Some of the impairments are associated with subarachnoid haemorrhage, whereas others (found in patients who underwent repair of unruptured aneurysms) are due to general effects of neurosurgery and perioperative management. Finally, some of the postoperative deficits are merely a reflection of premorbid weaknesses.

Long-term visual outcome after nonradical microsurgery patients with parasellar and cavernous sinus meningiomas.

OBJECTIVE: To determine the long-term visual outcome in patients with parasellar and cavernous sinus meningiomas treated with nonradical surgery. METHODS: Retrospective clinical review of 29 patients with parasellar or cavernous sinus meningiomas and visual sensory or ocular motor dysfunction at presentation, all of whom had at least 10 years of follow-up after initial diagnosis and treatment with nonradical surgery. RESULTS: Nineteen of 29 patients had a unilateral or bilateral optic neuropathy at presentation, and 7 patients developed a unilateral or bilateral optic neuropathy during a mean follow-up period of 13.6 years. However, 27 (93%) of 29 patients retained vision of 20/40 or better in at least one eye, and 14 patients (48%) retained vision of 20/40 or better in both eyes. New ocular motility deficits developed in 3 (10%) of 29 patients during the follow-up period. CONCLUSION: Radical surgery is not required to achieve long-term useful visual function for patients with parasellar or cavernous sinus meningiomas.