Histopathological Spectrum of Ovarian Tumors – A Descriptive Study.

Ovarian Cancer Is The Fifth Most Common Malignancy Among Women And Second Most Common Gynecologic Malignancy. It Is The Most Common Cause Of Death Due To Malignancy Of Female Genital Tract.1 Ovarian Malignancies Constitute About 4% Of The Total Cancers In Females And 25% Of Malignant Tumors Of The Female Genital Tract.2 In India, The Ovary Is Next In Importance To Cervix As The Seat Of Cancer Of Female Genital Tract. Surface Epithelial Ovarian Tumors Constitute Two Thirds Of All Ovarian Tumors And Malignant Forms Account For 90% Of Ovarian Cancers.3 They Exist In Different Histological Patterns And Exhibit Varying Degree Of Aggressiveness.4 Ovary Is Subjected To Monthly Endocrine And Traumatic Insults During Normal Ovulatory Cycles And Becomes Susceptible To Tumorogenesis. Repeated Ovulatory Rupture And Repair Theoretically Creates Opportunities For Malignant Gene Mutations. This May Explain The Apparent Protective Effects Of Oral Contraceptives, Late Menarche, Early Menopause, Multiparity, And Breast Feeding. Each Of These Factors Decrease The Occurrence Of Ovulation.5 Although No Age Group Is Free From The Tumors, Different Tumors Tend To Involve Different Age Groups Preferentially. The Complex Anatomy Of The Ovary And Its Peculiar Physiology With The Constant Cyclical Changes From Puberty To Menopause Give Rise To Number Of Cell Types, Each Of Which Is Capable Of Giving Rise To Tumors. Both Primary And Secondary Tumors Of The Ovaries Are Relatively Frequent Showing A Variety Of Histopathological Patterns.6 Since Germ Cells Are Totipotential, It Is Not Surprising That A Very Wide Variety Of Neoplasms May Develop From Them. Germ Cell Tumors Are The Commonest Ovarian Neoplasms In Young Age Group And Constitute Two Thirds Of Ovarian Tumors In This Age Group, Out Of Which One Third Are Malignant. These Tumors Account For 25-30% Of All Ovarian Tumors, With Great Majority Of Them In The Category Of Mature Cystic Teratoma, The Most Common Variety Of Ovarian Neoplasm In Humans.3 Ovarian Tumors In Children And Adolescent Girls Constitute An Important Part Of Gynecological Oncology. Detection Of These Tumors At Such A Young Age Creates Much Anxiety To Parents And Throws Up A Great Challenge To Doctors In Charge As The Question Of Operative Safety, Chance Of Malignancy And Prospects Of Future Child Bearing Associated With Treatment. Practice Of Fertility Sparing Surgery, Replacement Of Radiotherapy By Chemotherapy And Arrival Of Newer Chemotherapeutic Drugs Has Made The Prognosis Much Better Today. The Main Aim Lies In Distinguishing Ovarian Neoplasms From The Wide Spectrum Of Nonneoplastic Lesions. Despite The New Techniques In Imaging And Clinical Diagnosis, The Diagnosis Of Ovarian Tumors Is Primarily Dependent Upon Histopathological Examination. Determination Of Various Histologic Patterns Of Ovarian Tumors Is Very Important In Diagnosis As Well As Prognosis Of Ovarian Tumors. Prognosis Of The Tumors Can Also Be Predicted From The Degree Of Differentiation Of The Tumors. The Stage And Laterality Of The Tumors Also Indicates Their Nature For Example, Tumors In The Sex Cord Stromal Category Are Almost Always Confined To A Single Ovary. On The Other Hand, Approximately 65% Of The Metastatic Tumors Are Bilateral. In This Study, It Was Aimed To Find Out The Histopathological Patterns Which Are More Prevalent In Our Population And Whether They Are Significantly Different From Other Populations.7 Their Characteristics With Regard To Age, Size, Laterality, Gross Features Were Evaluated. Incidence Of Benign Versus Malignant Tumors Was Also Studied

Accuracy Optimization of Centrality Score Based Community Detection

Various concepts can be represented as a graph or the network. The network representation helps to characterize the varied relations between a set of objects by taking each object as a vertex and the interaction between them as an edge. Different systems can be modelled and analyzed in terms of graph theory. Community structure is a property that seems to be common to many networks. The division of the some objects into groups within which the connections or relations are dense, and the connections with other objects are sparser. Various research and data points proves that many real world networks has these communities or groups or the modules that are sub graphs with more edges connecting the vertices of the same group and comparatively fewer links joining the outside vertices. The groups or the communities exhibit the topological relations between the elements of the underlying system and the functional entities. The proposed approach is to exploit the global as well as local information about the network topologies. The authors propose a hybrid strategy to use the edge centrality property of the edges to find out the communities and use local moving heuristic to increase the modularity index of those communities. Such communities can be relevantly efficient and accurate to some applications. DOI: 10.17762/ijritcc2321-8169.15073

Drug utilization pattern in dermatology outpatient department at a tertiary care hospital in Navi Mumbai

Background: Skin diseases are common and cause a huge disease burden globally. Different class of drugs and combinational products are available in dermatology for treatment. Periodic prescription analysis in the form of drug utilization study can improve the quality of prescription and curb the menace of irrational prescribing. Aim and objective of the study were to study the prescribing pattern and drug utilization trends in Dermatology outpatient department at a tertiary care hospital in Navi Mumbai.Methods: A cross-sectional, observational study was conducted over a period of three months in dermatology department of a tertiary care teaching hospital, Navi-Mumbai. A total of 102 adult patients visiting dermatology OPD were included and their prescriptions were analyzed with WHO prescribing indicators and additional indices.Results: Analysis showed that the average number of drugs per prescription was 3.27. Percentage of drugs prescribed by generic name was 31.1%. Percentage of drugs prescribed from National Essential drug list (NEDL) was 44.2%. The commonest prescribed drugs were antihistaminics followed by antifungals. Oral tablets were the commonest prescribed dosage form.Conclusions: Antihistaminics and antifungals dominated the prescribing pattern in this study with restraint on polypharmacy, but showed ample scope for improvement to prescribe generic and selection of essential drugs

Re-establishing Responsiveness in a Case of Refractory Metastatic Rectal Cancer with a Personalized de novo Combination Regimen

Introduction: Encyclopedic Tumor Analysis (ETA) is multi-analyte, molecular and functional interrogation to identify latent vulnerabilities in solid tumors which can then be targeted in organ- and label-agnostic combination treatment regimens.Case Presentation: We describe here a case of metastatic rectal cancer in a 61-year-old male who was progressed on all prior Standard of Care (SoC) treatment modalities including surgery, chemotherapy and radiotherapy. We addressed disease recurrence via personalized therapy guided by ETA which revealed characteristic molecular heterogeneity in primary and metastatic lesions in terms of single nucleotide variations (SNVs) and gene copy number variations (CNVs).  Notably, a novel TBL1XR1 (Exon1) – PIK3CA (Exon 2) gene fusion was identified in the tumor along with gene copy number gains in TERT, IGF-1R, MYC, FGFR1 and EGFR genes.Conclusion: ETA based molecular analysis with synchronous in vitro chemo-sensitivity profiling strategy helped to define de novo combinatorial therapy regimen of targeted and cytotoxic drugs which countered disease progression at each instance and led to the durable regression of primary as well as metastatic lesions

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Adaptive, Iterative, Long-Term Personalized Therapy Management in a Case of Stage IV Refractory NSCLC

In this paper we report long-term therapy management based on iterative de novo molecular and cellular analysis in a case of metastatic non-small cell lung cancer (NSCLC), with prior history of treated colorectal cancer. In the described case temporal tumor evolution, emergent therapy resistance and disease recurrences were addressed via the administration of personalized label- and organ-agnostic treatments based on de novo tumor profiling. This adaptive and iterative treatment strategy countered disease progression at each instance and led to the durable regression of primary as well as metastatic lesions. Concurrently, serial evaluation of mutations in cell-free circulating tumor DNA (ctDNA) via liquid biopsy (LBx) was performed to monitor disease status, ascertain treatment response, identify emergent drug resistance and detect recurrence at sub-radiological levels. The treatment management strategy described herein effectively addressed multiple, sequential clinical conundrums for which viable options were unavailable under the current Standard of Care (SoC)

Optimally biosynthesized, PEGylated gold nanoparticles functionalized with quercetin and camptothecin enhance potential anti-inflammatory, anti-cancer and anti-angiogenic activities

The development of nano delivery systems is rapidly emerging area of nanotechnology applications where nanomaterials (NMs) are employed to deliver therapeutic agents to specific site in a controlled manner. To accomplish this, green synthesis of NMs is widely explored as an eco-friendly method for the development of smart drug delivery system. In the recent times, use of green synthesized NMs, especially metallic NMs have fascinated the scientific community as they are excellent carriers for drugs. This work demonstrates optimized green, biogenic synthesis of gold nanoparticles (AuNPs) for functionalization with quercetin (QT) and camptothecin (CPT) to enhance potential anti-inflammatory, anti-cancer and anti-angiogenic activities of these drugs. Results: Gold nanoparticles were optimally synthesized in 8 min of reaction at 90 °C, pH 6, using 4 mM of HAuCl4 and 4:1 ratio of extract: HAuCl4. Among different capping agents tested, capping of AuNPs with polyethylene glycol 9000 (PG9) was found best suited prior to functionalization. PG9 capped AuNPs were optimally functionalized with QT in 1 h reaction at 70 °C, pH 7, using 1200 ppm of QT and 1:4 ratio of AuNPs-PG9:QT whereas, CPT was best functionalized at RT in 1 h, pH 12, AuNPs-PG9:CPT ratio of 1:1, and 0.5 mM of CPT. QT functionalized AuNPs showed good anti-cancer activity ( IC50 687.44 μg/mL) against MCF-7 cell line whereas test of anti-inflammatory activity also showed excellent activity ( IC50 287.177 mg/L). The CAM based assessment of anti-angiogenic activity of CPT functionalized AuNPs demonstrated the inhibition of blood vessel branching confirming the anti-angiogenic effect. Conclusions: Thus, present study demonstrates that optimally synthesized biogenic AuNPs are best suited for the functionalization with drugs such as QT and CPT. The functionalization of these drugs with biogenic AuNPs enhances the potential anti-inflammatory, anti-cancer and anti-angiogenic activities of these drugs, therefore can be used in biomedical application