Survival trends for left and right sided colon cancer using population-based SEER database: A forty-five-year analysis from 1975 to 2019.

BACKGROUND: Survival differences between left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) has been previously reported with mixed results, with various study periods not accounting for other causes of mortality. PURPOSE: We sought to assess the trends in colon cancer cause- specific survival (CSS) and overall survival (OS) based on sidedness. METHOD: Fine-Gray competing risk and Cox models were used to analyze Surveillance, Epidemiology, and End Results (SEER) population-based cohort from 1975 to 2019. Various interval periods were identified based on the timeline of clinical adoption of modern chemotherapy (1975-1989, interval period A; 1990-2004, B; and 2005-2019, C). RESULTS: Of the 227,637 patients, 50.1% were female and 46.2% were RSCC. RSCC was more common for African Americans (51.5%), older patients (age ≥65; 51.4%), females (50.4%), while LSCC was more common among Whites (53.1%; p < 0.001), younger patients (age 18-49, 64.6%; 50-64, 62.3%; p < 0.001), males (58.1%; p < 0.001). The Median CSS for LSCC and RCC were 19.3 and 16.7 years respectively for interval period A (1975-1989). Median CSS for interval periods B and C were not reached (more than half of the cohort was still living at the end of the follow-up period). Adjusted CSS was superior for LSCC versus RSCC for the most recent interval period C (HR 0.89; 0.86-0.92; p < 0.001). LSCC consistently showed superior OS for all study periods. Stage stratification showed worse CSS for localized and regional LSCC in the earlier study periods, but the risk attenuated over time. However, left sided distant disease had superior CSS per stage for all interval periods. OS was better for LSCC irrespective of stage, with gradual improvement over time. CONCLUSION: LSCC was associated with superior survival compared to right sided tumors. With the adoption of modern chemotherapy regimens, prognosis between LSCC and RSCC became more divergent in favor of LSCC. Colon cancer clinical trials should strongly consider tumor sidedness as an enrollment factor.

The impact of COVID-19 on mortality, length of stay, and cost of care among patients with gastrointestinal malignancies: A propensity score-matched analysis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the coronavirus 19 (COVID-19) pandemic have had a lasting impact on the care of cancer patients. The impact on patients with gastrointestinal (GI) malignancies remains incompletely understood. We aimed to assess the impact of COVID-19 on mortality, length of stay (LOS), and cost of care among patients with GI malignancies, and identify differences in outcomes based on primary tumor site. METHODS: We analyzed discharge encounters collected from the National Inpatient Sample (NIS) between March 2020 and December 2020 using propensity score matching (PSM) and COVID-19 as the treatment effect. RESULTS: Of the 87,684 patient discharges with GI malignancies, 1892 were positive for COVID-19 (C+) and eligible for matching in the PSM model. Following PSM analysis, C+ with GI tumors demonstrated increased incidence of mortality compared to their COVID-19-negative (C-) counterparts (21.3% vs. 11.9%, p < 0.001). C+ patients with colorectal cancer (CRC) had significantly higher mortality compared to those who were C- (40% vs. 24%; p = 0.035). In addition, C+ patients with GI tumors had a longer mean LOS (9.4 days vs. 6.9 days; p < 0.001) and increased cost of care ($26,048.29 vs. $21,625.2; p = 0.001) compared to C- patients. C+ patients also had higher odds of mortality secondary to myocardial infarction relative to C- patients (OR = 3.54, p = 0.001). CONCLUSIONS: C+ patients with GI tumors face approximately double the odds of mortality, increased LOS, and increased cost of care compared to their C- counterparts. Outcome disparities were most pronounced among patients with CRC.

Race, age, and sex differences on the influence of obesity on colorectal cancer sidedness and mortality: A national cross-sectional study.

BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) sidedness is recognized as a prognostic factor for survival; left-sided colorectal cancer is associated with better outcomes than right-sided colon cancer (RsCC). We aimed to evaluate the influence of obesity on CRC sidedness and determine how race, age, and sex affect mortality among overweight and obese individuals. METHODS: A survey-weighted analysis was conducted using data obtained from the National Inpatient Sample between 2016 and 2019. RESULTS: Of the 24 549 patients with a diagnosis of CRC and a reported body mass index (BMI), 13.6% were overweight and 49.9% were obese. The race distribution was predominantly non-Hispanic Whites (69.7%), followed by Black (15.6%), Hispanic (8.7%), and other race (6.1%). Overweight (BMI: 25-29.9) and obese (BMI: ≥30) individuals were more likely to have RsCC (adjusted OR [aOR] = 1.28; 95% CI: 1.17-1.39, p < 0.001 and aOR = 1.45; 95% CI: 1.37-1.54, p < 0.001, respectively). Obese Black individuals were more likely to have RsCC as compared to their White counterparts (aOR = 1.23; 95% CI: 1.09-1.38). CONCLUSIONS: Obesity is associated with an increased risk of RsCC. In addition, racial disparities in CRC sidedness and outcomes are most pronounced among obese patients.

Second primary malignancies in patients with melanoma in situ: Insights from the surveillance, epidemiology, and end results program.

BACKGROUND: Melanoma in situ (MIS) is among the most frequently diagnosed cancers in the United States. Emerging data suggest that MIS is associated with an increased risk of developing a second primary malignancy (SPM). OBJECTIVES: To determine trends in MIS-associated SPMs and identify MIS-specific features that increase SPM risk. METHODS: In this retrospective population-based study, we identified 90,075 patients who were diagnosed with MIS between 1973 and 2015 from the Surveillance, Epidemiology, and End Results database. The risk of developing an SPM among these individuals was compared to individuals without a diagnosis of MIS. The risk of developing an SPM among patients with a diagnosis of MIS was also increased over time. RESULTS: Patients with a diagnosis of MIS had an increased relative risk (RR) of developing an SPM as compared to the general population with an identical age, sex, race, and follow-up period. The RR of a metachronous malignancy in MIS patients also increased over time, as follows: 1.16 (95 % CI: 1.07-1.26), 1.19 (95 % CI: 1.14-1.23), 1.30 (95 % CI: 1.27-1.33), and 1.52 (95 % CI: 1.49-1.56) in 1973-1982, 1983-1992, 1993-2002, and 2003-2015, respectively (P < 0.05). In addition, there was a direct correlation between the number of MIS lesions and SPM risk; ≥1, ≥2, and ≥3 tumors portended a 1.5-2, 2-3, and 4-5-fold increased risk of developing an SPM, respectively. CONCLUSIONS: MIS is associated with an increased risk of developing an SPM and therefore individuals with a history of MIS may benefit from close medical surveillance.

Expression of GFAP and Tau Following Blast Exposure in the Cerebral Cortex of Ferrets.

Blast exposures are a hallmark of contemporary military conflicts. We need improved preclinical models of blast traumatic brain injury for translation of pharmaceutical and therapeutic protocols. Compared with rodents, the ferret brain is larger, has substantial sulci, gyri, a higher white to gray matter ratio, and the hippocampus in a ventral position; these attributes facilitate comparison with the human brain. In this study, ferrets received compressed air shock waves and subsequent evaluation of glia and forms of tau following survival of up to 12 weeks. Immunohistochemistry and Western blot demonstrated altered distributions of astrogliosis and tau expression after blast exposure. Many aspects of the astrogliosis corresponded to human pathology: increased subpial reactivity, gliosis at gray-white matter interfaces, and extensive outlining of blood vessels. MRI analysis showed numerous hypointensities occurring in the 12-week survival animals, appearing to correspond to luminal expansions of blood vessels. Changes in forms of tau, including phosphorylated tau, and the isoforms 3R and 4R were noted using immunohistochemistry and Western blot in specific regions of the cerebral cortex. Of particular interest were the 3R and 4R isoforms, which modified their ratio after blast. Our data strongly support the ferret as an animal model with highly translational features to study blast injury.

Cranial molding on neonates in Ghana: mothers' perspective and their knowledge on potential harm to babies' brain.

BACKGROUND AND OBJECTIVES: Traditional cranial molding is an ancient practice prevalent in Ghana. In this work, we aimed at assessing mothers'/caregivers' perspective and their knowledge on potential harm of cranial molding on neonates. METHODS: Two hundred and one (201) nursing mothers with babies aged 1-12 months were sampled in a cross-sectional study using questionnaires. We assessed the mothers'/caregivers' reasons for cranial molding, their perceived benefits of this practice, and their knowledge about the potential harm this practice pose to babies. RESULTS: Sixty four percent (64%) of mothers confirmed they practice cranial molding on their babies either on their own or through the assistance of a caretaker. However, 72% of all mothers/caregivers did not know this practice has the potential to harm the baby in any way. Mothers'/caregivers' reasons for this practice included the following: to achieve a more "beautiful" head shape, hasten the healing of the fontanelle, and limit head growth. There was a significant association between the mothers'/caregivers' level of education and the practice of cranial molding (p value < 0.05). However, there was no association between head symmetry and cranial molding (p value > 0.05). CONCLUSIONS AND IMPLICATIONS: Majority of mothers/caregivers were actively engaged in cranial molding on neonates but remain ignorant about the potential harm this practice could have on their babies. Mothers/caregivers therefore need to be educated about the potential harm posed by traditional cranial molding on neonates.

Racial Disparity in Incidence and Survival for Gastrointestinal Stromal Tumors (GISTs): an Analysis of SEER Database.

BACKGROUND: Gastrointestinal tumors (GISTs) represent the most common mesenchymal tumors of the gastrointestinal tract. There has been limited data on GIST incidence and survival disparities between ethnic groups. AIMS: Assess disparities in incidence and survival among race in the USA in the era of available GIST histologic codes and treatment. METHODS: We queried Surveillance, Epidemiology, and End Results (SEER) database for GIST from 2002 to 2015, with diagnostic code 8936. RESULTS: Of the 7204 patients identified, 4928 (68.4%) were White, 1308 (18.2%) African American (AA), and 968 (13.4%) were classified as "Other" (American Indian/Alaskan Native, Asian/Pacific Islander). The overall incidence rate (IR) was 0.75 per 100,000. IR was highest among AA at 1.37/100,000, but 0.65/100,000 for Whites, 1.10/100,000 for Asians/Pacific Islanders, and 0.28/100,000 for American Indians/Alaskan Natives. The GIST incidence was twice as high for AA as for Whites (rate ratio [RR]: 2.12; 95% CI: 1.98-2.26; p < 0.001). There was higher proportion of Whites than AA, who underwent surgical extirpation. Median overall survival (OS) and GIST specific survival (GSS) were not reached for all race, which indicates more than half of the patients were still alive at end of follow-up period. In multivariate Cox model, belonging to "Other" had better OS (adjusted hazard ratio [aHR]; 0.73, 95% CI: 0.55-0.95, P = 0.021) for GIST, but no difference in prognosis and OS for AA and White [(aHR for whites; 0.84, 95% CI: 0.69-1.02, P = 0.071), AA = reference]. There was no difference in GSS among races. CONCLUSIONS: Significant racial disparity in incidence and overall survival for GIST exists, and efforts should be made to bridge this gap and improve outcomes for all races. The overall incidence rate for GIST was noted to be 7.5 per 1 million, and IR of GIST was twice as high for African Americans as compared to Whites. The "Other" racial group (American Indians/Alaskan Natives, Asians, and Pacific Islanders) had superior OS as compared to African Americans and Whites.

The effect of Zika virus infection in the ferret.

Although initial observations of infections with the Zika virus describe a mild illness, more recent reports show that infections by Zika result in neurotropism. In 2015, substantial congenital malformations were observed, with numerous infants born with microcephaly in Brazil. To study the underlying mechanism and effects of the disease, it is critical to find suitable animal models. Rodents lack an immune system parallel to humans and also have lissencephalic brains, which are likely to react differently to infections. As the smallest gyrencephalic mammal, ferrets may provide an important animal model to study the Zika virus, as their brains share many characteristics with humans. To evaluate the prospect of using ferrets to study Zika virus infection, we injected seven pregnant jills with the PR strain subcutaneously on gestational day 21, corresponding to the initiation of corticogenesis. These injections resulted in mixed effects. Two animals died of apparent infection, and all kits were resorbed in another animal that did not die. The other four animals remained pregnant until gestational day 40, when the kits were delivered by caesarian section. We evaluated the animals using CT, MRI, diffusion tensor imaging, and immunohistochemistry. The kits displayed a number of features compatible with an infection that impacted both the brain and skull. The outcomes, however, were variable and differed within and across litters, which ranged from the absence of observable abnormalities to prominent changes, suggesting differential vulnerability of kits to infection by the Zika virus or to subsequent mechanisms of neurodevelopmental disruption.

Distribution and Cellular Localization of KCC2 in the Ferret Neocortex.

KCC2 (a brain-specific potassium-chloride cotransporter) affects development of the cerebral cortex, including aspects of neuronal migration and cellular maturation and differentiation. KCC2 also modulates chloride homeostasis by influencing the switch of GABA from depolarizing in young neurons to hyperpolarizing in mature neurons. We describe the expression pattern, regional distribution, and cellular colocalization of KCC2 in the ferret cortex in normal kits and those treated with methylazoxymethanol acetate (MAM). We earlier developed a model of impaired cortical development by injecting MAM during mid-cortical gestation, which briefly interferes with neuronal production and additionally results in increased levels of KCC2 at P0. Using immunohistochemistry, we show a shift in KCC2 expression during development, being high in the subplate at P0, repositioning into a subtle laminar pattern in the neocortex at P7-P14, and becoming homogeneous at P35. KCC2 colocalizes with neuronal markers in the developing and mature cerebral cortex of normal ferrets and those treated with MAM, but shows a differential pattern of expression at different ages and locates in distinct cellular compartments during development. Subcellular localization shows that KCC2 predominantly situates in the membrane fraction of neocortical samples. These findings reveal that KCC2 colocalizes differentially with neurons and its expression pattern alters during development.