The interactions of SARS-CoV-2 with cocirculating pathogens: Epidemiological implications and current knowledge gaps.

Despite the availability of effective vaccines, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that cocirculation with other pathogens and resulting multiepidemics (of, for example, COVID-19 and influenza) may become increasingly frequent. To better forecast and control the risk of such multiepidemics, it is essential to elucidate the potential interactions of SARS-CoV-2 with other pathogens; these interactions, however, remain poorly defined. Here, we aimed to review the current body of evidence about SARS-CoV-2 interactions. Our review is structured in four parts. To study pathogen interactions in a systematic and comprehensive way, we first developed a general framework to capture their major components: sign (either negative for antagonistic interactions or positive for synergistic interactions), strength (i.e., magnitude of the interaction), symmetry (describing whether the interaction depends on the order of infection of interacting pathogens), duration (describing whether the interaction is short-lived or long-lived), and mechanism (e.g., whether interaction modifies susceptibility to infection, transmissibility of infection, or severity of disease). Second, we reviewed the experimental evidence from animal models about SARS-CoV-2 interactions. Of the 14 studies identified, 11 focused on the outcomes of coinfection with nonattenuated influenza A viruses (IAVs), and 3 with other pathogens. The 11 studies on IAV used different designs and animal models (ferrets, hamsters, and mice) but generally demonstrated that coinfection increased disease severity compared with either monoinfection. By contrast, the effect of coinfection on the viral load of either virus was variable and inconsistent across studies. Third, we reviewed the epidemiological evidence about SARS-CoV-2 interactions in human populations. Although numerous studies were identified, only a few were specifically designed to infer interaction, and many were prone to multiple biases, including confounding. Nevertheless, their results suggested that influenza and pneumococcal conjugate vaccinations were associated with a reduced risk of SARS-CoV-2 infection. Finally, fourth, we formulated simple transmission models of SARS-CoV-2 cocirculation with an epidemic viral pathogen or an endemic bacterial pathogen, showing how they can naturally incorporate the proposed framework. More generally, we argue that such models, when designed with an integrative and multidisciplinary perspective, will be invaluable tools to resolve the substantial uncertainties that remain about SARS-CoV-2 interactions.

Using LASSO Regression to Estimate the Population-Level Impact of Pneumococcal Conjugate Vaccines.

Pneumococcal conjugate vaccines (PCVs) protect against diseases caused by Streptococcus pneumoniae, such as meningitis, bacteremia, and pneumonia. It is challenging to estimate their population-level impact due to the lack of a perfect control population and the subtleness of signals when the endpoint-such as all-cause pneumonia-is nonspecific. Here we present a new approach for estimating the impact of PCVs: using least absolute shrinkage and selection operator (LASSO) regression to select variables in a synthetic control model to predict the counterfactual outcome for vaccine impact inference. We first used a simulation study based on hospitalization data from Mexico (2000-2013) to test the performance of LASSO and established methods, including the synthetic control model with Bayesian variable selection (SC). We found that LASSO achieved accurate and precise estimation, even in complex simulation scenarios where the association between the outcome and all control variables was noncausal. We then applied LASSO to real-world hospitalization data from Chile (2001-2012), Ecuador (2001-2012), Mexico (2000-2013), and the United States (1996-2005), and found that it yielded estimates of vaccine impact similar to SC. The LASSO method is accurate and easily implementable and can be applied to study the impact of PCVs and other vaccines.

Differences in life attitudes between general population and hospitalized psychosomatic patients: a comparative cross-sectional study.

To compare the extent to which value-based life attitudes measured by means of the Life Attitude Profile (LAP-R) could differ between the general population and people suffering from mental disorders hospitalized in a psychosomatic ward. Cross-sectional comparative study between a sample of general population (n = 409) and a sample of unselected patients (n = 147) at admission in a psychosomatic ward. Comparisons were carried out by means of Cronbach's alpha, correlation matrix, t-tests, robust multivariate linear regression models (MLRM), and using propensity scores. The internal consistency of LAP-R is good (alpha = 0.90). Divergent validity with BFI dimensions is widely given. In MLRM general population scored higher for the indexes 'personal meaning' and 'existential transcendence', whereas psychosomatic patients for the dimensions 'responsibleness', 'death acceptance', 'goal seeking' and especially 'existential vacuum'. Sex, partnership and schooling display few associations. Neuroticism is negatively and agreeableness positively associated with life attitudes considered as protective. Norm values and differences were stratified by age ranges. This study demonstrates that basic human attitudes like personal transcendence, personal meaning, having a biographically supported mission in life, and belief in a reason for existence are so fundamental for individuals that they are to some degree given independently of having a mental disorder or not. Neuroticism is a risk trait and agreeableness a protective trait facing life attitudes. The findings of this study indicate that people suffering from mental disorders treated in a specialized psychosomatic unit in a general hospital have important value-based resources and simultaneously higher levels of existential vacuum that have to be considered in treatment planning but should also be embedded in a therapeutic alliance. The existential vacuum deserves special consideration in the treatment of patients, especially facing risk of suicide.

The pitfalls of inferring virus-virus interactions from co-detection prevalence data: application to influenza and SARS-CoV-2.

There is growing experimental evidence that many respiratory viruses-including influenza and SARS-CoV-2-can interact, such that their epidemiological dynamics may not be independent. To assess these interactions, standard statistical tests of independence suggest that the prevalence ratio-defined as the ratio of co-infection prevalence to the product of single-infection prevalences-should equal unity for non-interacting pathogens. As a result, earlier epidemiological studies aimed to estimate the prevalence ratio from co-detection prevalence data, under the assumption that deviations from unity implied interaction. To examine the validity of this assumption, we designed a simulation study that built on a broadly applicable epidemiological model of co-circulation of two emerging or seasonal respiratory viruses. By focusing on the pair influenza-SARS-CoV-2, we first demonstrate that the prevalence ratio systematically underestimates the strength of interaction, and can even misclassify antagonistic or synergistic interactions that persist after clearance of infection. In a global sensitivity analysis, we further identify properties of viral infection-such as a high reproduction number or a short infectious period-that blur the interaction inferred from the prevalence ratio. Altogether, our results suggest that ecological or epidemiological studies based on co-detection prevalence data provide a poor guide to assess interactions among respiratory viruses.

Modeling influenza seasonality in the tropics and subtropics.

Climate drivers such as humidity and temperature may play a key role in influenza seasonal transmission dynamics. Such a relationship has been well defined for temperate regions. However, to date no models capable of capturing the diverse seasonal pattern in tropical and subtropical climates exist. In addition, multiple influenza viruses could cocirculate and shape epidemic dynamics. Here we construct seven mechanistic epidemic models to test the effect of two major climate drivers (humidity and temperature) and multi-strain co-circulation on influenza transmission in Hong Kong, an influenza epidemic center located in the subtropics. Based on model fit to long-term influenza surveillance data from 1998 to 2018, we found that a simple model incorporating the effect of both humidity and temperature best recreated the influenza epidemic patterns observed in Hong Kong. The model quantifies a bimodal effect of absolute humidity on influenza transmission where both low and very high humidity levels facilitate transmission quadratically; the model also quantifies the monotonic but nonlinear relationship with temperature. In addition, model results suggest that, at the population level, a shorter immunity period can approximate the co-circulation of influenza virus (sub)types. The basic reproductive number R0 estimated by the best-fit model is also consistent with laboratory influenza survival and transmission studies under various combinations of humidity and temperature levels. Overall, our study has developed a simple mechanistic model capable of quantifying the impact of climate drivers on influenza transmission in (sub)tropical regions. This model can be applied to improve influenza forecasting in the (sub)tropics in the future.

A Novel Human Sex Difference: Male Sclera Are Redder and Yellower than Female Sclera.

In a seminal study, Kobayashi and Kohshima (1997) found that the human sclera-the white of the eye-is unique among primates for its whitish color, and subsequent work has supported the notion that this coloration underlies the human ability to gaze follow. Kobayashi and Kohshima also claimed that there is no significant sex difference in sclera color, though no data were presented to support the claim. We investigated sclera color in a standardized sample of faces varying in age and sex, presenting the first data comparing male and female sclera color. Our data support the claim that indeed there is a sex difference in sclera color, with male sclera being yellower and redder than female sclera. We also replicated earlier findings that female sclera vary in color across the adult lifespan, with older sclera appearing yellower, redder, and slightly darker than younger sclera, and we extended these findings to male sclera. Finally, in two experiments we found evidence that people use sclera color as a cue for making judgements of facial femininity or masculinity. When sclera were manipulated to appear redder and yellower, faces were perceived as more masculine, but were perceived as more feminine when sclera were manipulated to appear less red and yellow. Though people are typically unaware of the sex difference in sclera color, these findings suggest that people nevertheless use the difference as a visual cue when perceiving sex-related traits from the face.

Forecasting influenza in Europe using a metapopulation model incorporating cross-border commuting and air travel.

Past work has shown that models incorporating human travel can improve the quality of influenza forecasts. Here, we develop and validate a metapopulation model of twelve European countries, in which international translocation of virus is driven by observed commuting and air travel flows, and use this model to generate influenza forecasts in conjunction with incidence data from the World Health Organization. We find that, although the metapopulation model fits the data well, it offers no improvement over isolated models in forecast quality. We discuss several potential reasons for these results. In particular, we note the need for data that are more comparable from country to country, and offer suggestions as to how surveillance systems might be improved to achieve this goal.

Divergent patterns of confrontation with death using the Anticipated Farewell to Existence Questionnaire (AFEQT): a cross-sectional comparative study of four samples with increasing proximity to death.

BACKGROUND: Based on the concept of "Daseinsverabschiedung", an anthropological theory of "Anticipated Farewell to Existence" (AFE) was suggested on the basis of six grounding dimensions: selfhood, interpersonality, temporality, corporeality, worldliness, and transcendence, which are activated in a genuine manner facing death. The purpose of the study is to quantitatively compare the extent of confrontation with death between dying people in palliative care and those in other stages of life by means of the Anticipated Farewell to Existence Questionnaire" (AFEQT), based on these dimensions. METHODS: The sample (N = 485) consists of dying individuals in palliative wards and hospices (n = 121); old people living in nursing homes not suffering from a mortal disease (n = 62); young adults (n = 152), and middle-aged adults (n = 150). The design is cross-sectional and analytical. The relevance of anticipated farewell to existence was measured by means of the AFEQT. The internal consistency of the AFEQT was assessed using Cronbach's alpha and convergent validity by means of dimensions of the Life Attitude Profile-Revised (LAP-R). Differences between groups and associations with control variables were estimated by means of multiple regression models, including propensity scores. RESULTS: Cronbach's alpha for AFEQT was > 0.80 for the whole test and all subsamples, but < 0.70 for most dimensions in dying people. Correlations between each dimension and corresponding two factors was almost overall r > 0.80, p < 0.001. Good convergent validity between dimensions of AFEQT and of Life Attitude Profile-Revised in young and middle-aged participants showed correlations for superordinate indices between -0.23 and 0.72, and an overall p < 0.001. Dying people scored significantly higher for all dimensions, especially "altruistic preoccupation" and "reconciliation with existence" than people in other life stages (p < 0.01- < 0.001). Personality traits of "openness" and "agreeableness" are positively associated with higher scoring of AFEQT dimensions. About 77% of dying participants reported a personal benefit through the interview questions. CONCLUSIONS: With proximity to death, the anthropological dimensions proposed scored significant higher than in other stages of life, reflecting a stronger awareness, confrontation and reconciliation with the end of their own life. These dimensions, especially preoccupation for related persons and coexistence of acceptance and struggle with death have to be taken into account in a sensitive way by supporting dialogues with dying people and their relatives. TRIAL REGISTRATION: Observational cross-sectional study.

Amelioration of Cognitive and Behavioral Deficits after Traumatic Brain Injury in Coagulation Factor XII Deficient Mice.

Based on recent findings that show that depletion of factor XII (FXII) leads to better posttraumatic neurological recovery, we studied the effect of FXII-deficiency on post-traumatic cognitive and behavioral outcomes in female and male mice. In agreement with our previous findings, neurological deficits on day 7 after weight-drop traumatic brain injury (TBI) were significantly reduced in FXII-/- mice compared to wild type (WT) mice. Also, glycoprotein Ib (GPIb)-positive platelet aggregates were more frequent in brain microvasculature of WT than FXII-/- mice 3 months after TBI. Six weeks after TBI, memory for novel object was significantly reduced in both female and male WT but not in FXII-/- mice compared to sham-operated mice. In the setting of automated home-cage monitoring of socially housed mice in IntelliCages, female WT mice but not FXII-/- mice showed decreased exploration and reacted negatively to reward extinction one month after TBI. Since neuroendocrine stress after TBI might contribute to trauma-induced cognitive dysfunction and negative emotional contrast reactions, we measured peripheral corticosterone levels and the ration of heart, lung, and spleen weight to bodyweight. Three months after TBI, plasma corticosterone levels were significantly suppressed in both female and male WT but not in FXII-/- mice, while the relative heart weight increased in males but not in females of both phenotypes when compared to sham-operated mice. Our results indicate that FXII deficiency is associated with efficient post-traumatic behavioral and neuroendocrine recovery.

Development and validation of influenza forecasting for 64 temperate and tropical countries.

Accurate forecasts of influenza incidence can be used to inform medical and public health decision-making and response efforts. However, forecasting systems are uncommon in most countries, with a few notable exceptions. Here we use publicly available data from the World Health Organization to generate retrospective forecasts of influenza peak timing and peak intensity for 64 countries, including 18 tropical and subtropical countries. We find that accurate and well-calibrated forecasts can be generated for countries in temperate regions, with peak timing and intensity accuracy exceeding 50% at four and two weeks prior to the predicted epidemic peak, respectively. Forecasts are significantly less accurate in the tropics and subtropics for both peak timing and intensity. This work indicates that, in temperate regions around the world, forecasts can be generated with sufficient lead time to prepare for upcoming outbreak peak incidence.

[Hypoglycaemia and seizures in a 32-year-old woman with maple syrup urine disease]. / Hypoglykämien und Krampfanfälle bei einer 32­jährigen Patientin mit Ahornsiruperkrankung.

A 32-year-old woman with maple syrup urine disease presented with recurring episodes with hypoglycaemia and cerebral seizures. In most cases a connection to the inborn metabolic disorder is assumed, resulting in symptomatic treatment. Due to these treatments invasive procedures are required. This leads to prescriptions of multiple medications and medical aids. After 2 years of unexplained symptoms a routine examination led to the diagnosis of factitious disorder. The patient received the offer for psychiatric/psychotherapeutic treatment. Further prognosis remains uncertain.

[Data on the sexual health of providers and clients of sexual services for men who have sex with men in Germany]. / Daten zur sexuellen Gesundheit von Anbietern und Kunden sexueller Dienste bei in Deutschland lebenden Männern, die Sex mit Männern haben.

Little is known about the sexual health of male providers and clients of transactional sex. The data of participants of the European MSM Internet Survey (EMIS-DE; N = 50,086) who live in Germany were analysed. The outcomes were testing for and diagnoses of HIV and other sexually transmitted infections (STIs), partner numbers, illicit drug use, and sexual happiness in two populations: (1) men who offered and (2) men who paid for transactional sex in the past 12 months.In the age group of under 30 years (n = 19,138), providers of sexual services (escorts) were compared with non-providers; in the age group of 30 years and above (n = 30,948), we compared men who paid for sexual services with those who did not. We applied univariable and multinomial, multivariable logistic regression analyses in both age groups.Of those under the age of 30, 8% (n = 1529) had been paid for sex in the last 12 months, of which 49% were only paid once or twice. Escorts had lower educational achievements, lived more commonly in large cities, were more often born abroad, self-defined less frequently as gay, and were more frequently single. They reported higher numbers of sex partners, more drug use, and more sexual happiness. Escorts were more frequently tested for HIV and STIs, and among the tested, more diagnoses of HIV and STIs were reported, but those with HIV were less likely to be treated.Among those over 30 years, 11% (n = 3334) had paid for sex, the majority (58%) only once or twice. Payers were older, lived more commonly in large cities, and were more likely to be single, bisexual, or living with a woman. Clients used more illicit drugs, sexual enhancement drugs, and sedatives, but reported less sexual happiness. They were less likely to be tested for HIV and STIs.

Factors associated with unprotected anal sex with multiple non-steady partners in the past 12 months: results from the European Men-Who-Have-Sex-With-Men Internet Survey (EMIS 2010).

BACKGROUND: Practising unprotected anal intercourse (UAI) with high numbers of partners is associated with increased risk for acquiring and transmitting HIV and other sexually transmitted infections. Our aim was to describe factors associated with UAI with multiple partners in a large sample of MSM from 38 European countries recruited for an online survey in 2010. METHODS: Data are from the European Men-Who-Have-Sex-With-Men Internet Survey (EMIS). The analysis was restricted to men who reported any anal sex with a non-steady partner in the past 12 months, and who were either never diagnosed with HIV, or who had been diagnosed with HIV more than 12 months ago, reported a detectable viral load and did not exclusively serosort (n = 91,477). Multivariable logistic regression was used to compare men reporting UAI with four or more (4+) non-steady partners to two comparison groups: a) no UAI with non-steady partners, and b) UAI with 1-3 non-steady partners. RESULTS: Overall, 9.6% of the study population reported UAI with 4+ partners in the past 12 months. In both models, factors consistently associated with this behaviour were: having been diagnosed with HIV, lower educational levels, use of nitrite inhalants, drugs associated with sex and parties, or erectile dysfunction drugs in the past 4 weeks, using sex-on-site venues in the past 4 weeks, buying or selling sex in the past 12 months, having experienced physical violence due to sexual attraction to men in the past 12 months, reporting sexual happiness, being out to all or almost all of one's acquaintances, and knowing that ART reduces HIV transmissibility. CONCLUSIONS: Effective antiretroviral treatment drastically reduces HIV transmission for men diagnosed with HIV, irrespective of partner numbers. Apart from reducing partner numbers or increasing condom use no other recommendations are currently in place to reduce the risk of HIV acquisition and onward transmission for HIV-negative men practicing UAI with multiple partners. A range of factors were identified as associated with UAI with four or more partners which allow the strengthening and targeting of prevention strategies to reduce HIV transmission risks resulting from condomless anal intercourse with multiple partners.

Fat Intravasation from Intraosseous Flush and Infusion Procedures.

STUDY HYPOTHESIS: The primary study objective was to delineate the procedural aspects of intraosseous (IO) infusions responsible for fat intravasation by testing the hypothesis that the fat content of effluent blood increases during IO infusions. METHODS: IO cannulas were inserted into the proximal tibiae of 35 anesthetized swine (Sus scrofa, 50.1 ± 3.5 kg) and intravasated fat was assessed using a lipophilic fluoroprobe (Nile red) and by vascular ultrasound imaging. Effluent blood bone marrow fat was assessed at baseline, during flush, and with regimens of controlled infusion pressures (73-300 mmHg) and infusion flow rates (0.3-3.0 mL per second). Fat intravasation was also assessed with IO infusions at different tibial cannulation sites and in the distal femur. In 7 animals, the lipid uptake of alveolar macrophages and lung tissue assessed for fat embolic burden using oil red O stain 24 hours post infusion. Additionally, bone marrow shear-strain was assessed radiographically with IO infusions. RESULTS: Fat intravasation was observed during all IO infusion regimens, with subclinical pulmonary fat emboli persisting 24 hours post infusion. It was noted that initial flush was a significant factor in fat intravasation, low levels of intravasation occurred with infusions ≤300 mmHg, fat intravasation and bone marrow shear-strain increased with IO infusion rates, and intravasation was influenced by cannula insertion site. Ultrasound findings suggest that echogenic particles consistent with fat emboli are carried in fast and slow venous blood flow fields. Echo reflective densities were observed to rise to the nondependent endovascular margins and coalesce in accordance with Stoke's law. In addition, ultrasound findings suggested that intravasated bone marrow fat was thrombogenic. CONCLUSION: Results suggest that in swine the intravasation of bone marrow fat is a common consequence of IO infusion procedures and that its magnitude is influenced by the site of cannulation and infusion forces. Although the efficacy and benefits of IO infusions for emergent care are well established, emergency care providers also should be cognizant that infusion procedures affect bone marrow fat intravasation.

Factors associated with sexual risk behaviors with non-steady partners and lack of recent HIV testing among German men who have sex with men in steady relationships: results from a cross-sectional internet survey.

BACKGROUND: Recent evidence suggests that the majority of HIV transmissions among men who have sex with men (MSM) occur between steady partners. We sought to determine factors associated with HIV transmission risks in steady partnerships. METHODS: Data is from the German cross-sectional 2013 Gay Men and AIDS survey. The study population was HIV-negative or untested men reporting a steady partnership and at least one non-steady anal sex partner in the previous year. Bivariate and multivariate logistic regression was used to determine which of several independent variables best predicted both unprotected anal intercourse (UAI) with a non-steady partner and lack of HIV testing in the past year (high-risk outcome group). RESULTS: The study population consisted of 1731 men. Among individuals in the outcome group (n = 271), 67% reported UAI with a non-steady partner of unknown status and 9% reported UAI with a non-steady HIV-positive partner in the past 12 months; 55% considered themselves to be at low risk for HIV acquisition. In multivariate analyses (n = 1304), participants were statistically more likely to belong to the outcome group if they reported UAI with their steady partner in the past year (OR = 2.21), did not know their steady partner's HIV status (OR = 1.98), or agreed that condoms were disruptive during sex (OR = 3.82 (strongly agree), OR = 2.19 (agree)). Participants were less likely to belong to the outcome group if they were out to their primary doctor (OR = 0.54), were well-educated about post-exposure prophylaxis (OR = 0.46), had sought information on HIV in the past year and kept condoms in an accessible place (OR = 0.20), or believed that insisting on condoms would lead partners to assume they were HIV-negative (OR = 0.20). Participants in the outcome group were more likely to say they would use HIV home tests (OR = 1.58) or pre-exposure prophylaxis (OR = 2.11). CONCLUSIONS: Based on our results, we reflect on HIV prevention measures that should be improved in order to better target behaviors that may lead to HIV transmission between MSM in steady relationships. In particular, we highlight the need for multifaceted interventions focusing not only on members of the at-risk community themselves, but on communities as a whole.

Conditionally reprogrammed cells represent a stem-like state of adult epithelial cells.

The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y-27632, conditionally induces an indefinite proliferative state in primary mammalian epithelial cells. These conditionally reprogrammed cells (CRCs) are karyotype-stable and nontumorigenic. Because self-renewal is a recognized property of stem cells, we investigated whether Y-27632 and feeder cells induced a stem-like phenotype. We found that CRCs share characteristics of adult stem cells and exhibit up-regulated expression of α6 and ß1 integrins, ΔNp63α, CD44, and telomerase reverse transcriptase, as well as decreased Notch signaling and an increased level of nuclear ß-catenin. The induction of CRCs is rapid (occurs within 2 d) and results from reprogramming of the entire cell population rather than the selection of a minor subpopulation. CRCs do not overexpress the transcription factor sets characteristic of embryonic or induced pluripotent stem cells (e.g., Sox2, Oct4, Nanog, or Klf4). The induction of CRCs is also reversible, and removal of Y-27632 and feeders allows the cells to differentiate normally. Thus, when CRCs from ectocervical epithelium or tracheal epithelium are placed in an air-liquid interface culture system, the cervical cells form a well differentiated stratified squamous epithelium, whereas the tracheal cells form a ciliated airway epithelium. We discuss the diagnostic and therapeutic opportunities afforded by a method that can generate adult stem-like cells in vitro without genetic manipulation.

Locally advanced pancreatic cancer: Is surgical palliation associated with improved clinical outcome relative to medical palliation?

BACKGROUND: The value of palliative surgery in pancreatic cancer is not well-defined. METHODS: We queried the National Cancer Database for patients undergoing curative-intent resection, palliative surgery or medical palliation for clinical stage cT4N0-2M0 pancreatic cancer. Cohorts were 1:1:1 propensity-score-matched for comorbidities and stage. Kaplan-Meier method was used to compare overall survival for matched cohorts. RESULTS: 9,107 patients met inclusion criteria: 3,567 (39 â€‹%) underwent curative intent surgery, 1608 (18 â€‹%) surgical palliation, 3932 (43 â€‹%) medical palliation. Patients undergoing resection and surgical palliation had significant hospitalizations (11.0 â€‹± â€‹0.4 vs. 10.0 â€‹± â€‹0.3 days; p â€‹= â€‹0.821) and rates of readmission (8.1 â€‹% vs. 2.0 â€‹%; p â€‹< â€‹0.001). Patients undergoing surgical palliation demonstrated marginal increases in survival relative to those undergoing medical palliation (8.54 vs. 7.36 months; p â€‹< â€‹0.0001). CONCLUSION: In patients undergoing care for locally advanced pancreatic cancer, palliative surgery is associated with marginal improvement in survival but significant lengths of hospitalization and risk of readmission.

Fragmented care in localized pancreatic cancer: Is commission on cancer accreditation associated with improved overall survival?

BACKGROUND: Prior studies of fragmentation of care in pancreatic cancer have not adjusted for indicators of hospital quality such as Commission on Cancer accreditation. The effect of fragmentation of care has not been well defined. METHODS: We queried the National Cancer Database to identify patients undergoing pancreaticoduodenectomy and distal pancreatectomy with perioperative systemic therapy for clinical stages I-III pancreatic cancer between 2006 and 2019. Patients who received systemic therapy at a center different than the center performing surgery were categorized as having fragmentation of care. Patients having fragmentation of care were further categorized on the basis of whether (fragmentation of care Commission on Cancer) or not (fragmentation of care non-Commission on Cancer) systemic therapy was administered at a facility accredited by the Commission on Cancer. RESULTS: A total of 11,732 patients met inclusion criteria; 5,668 (48.3%) underwent fragmentation of care, and 3,426 (29.2%) fragmentation of care non-Commission on Cancer. Patients undergoing fragmentation of care non-Commission on Cancer were less likely to receive neoadjuvant systemic therapy than those undergoing fragmentation of care Commission on Cancer or non-fragmented care (27.7% vs 40.1% vs 36.8%, P < .001). On Cox analysis, advanced age, comorbid disease, node-positive disease, and facility type were associated with risk of overall survival. Fragmentation of care was not (adjusted hazard ratio = 0.99, 95% confidence interval [0.94-1.06], P = .8). On Kaplan-Meier analysis, there were no significant differences in 5-year overall survival between treatment cohorts. CONCLUSION: In patients undergoing fragmentation of care for localized pancreatic cancer, those treated with systemic therapy in Commission on Cancer accredited facilities are more likely to be given neoadjuvant therapy but demonstrate no significant improvement in survival relative to those undergoing non-fragmented care or those undergoing fragmentation of care but receiving systemic therapy in nonaccredited facilities.

Locally Advanced Adenocarcinoma of the Esophagus: Is Esophagectomy Associated with Improved Overall Survival?

BACKGROUND: Esophagectomy in locally advanced esophageal adenocarcinoma is challenging and carries risk. The value of esophagectomy in locally advanced esophageal adenocarcinoma is not well-defined. STUDY DESIGN: The National Cancer Database was used to identify patients with cT4 esophageal adenocarcinoma from 2004 to 2020. Multivariable regression was used to identify factors associated with use of esophagectomy. Cox modeling was used to identify factors associated with all-cause mortality. Patients undergoing esophagectomy were 1:1 propensity score-matched to patients treated nonsurgically. Kaplan-Meier analysis was used to compare 5-year overall survival (OS). RESULTS: A total of 3,703 patients met inclusion criteria. Of those, 541 (15%) underwent esophagectomy, and 3,162 (85%) did not. Age 65 years or less (adjusted odds ratio [aOR] 1.69, 95% CI 1.33 to 2.14), White race (aOR 2.98, 95% CI 2.24 to 3.96), treatment in academic centers (aOR 1.64, 95% CI 1.33 to 2.02), private insurance (aOR 1.88, 95% CI 1.50 to 2.36), and tumors less than 6 cm (aOR 1.86, 95% CI 1.44 to 2.40) were associated with use of esophagectomy. Government of lack of insurance (hazard ratio [HR] 1.23, 95% CI 1.12 to 1.35), income <$46,000 (HR 1.11, 95% CI 1.03 to 1.20), treatment in nonacademic centers (HR 1.16, 95% CI 1.07 to 1.25), Charlson-Deyo Comorbidity Index 1 or more (HR 1.22, 95% CI 1.12 to 1.32), and tumors 6 cm or more (HR 1.20, 95% CI 1.09 to 1.32) were associated with risk of all-cause mortality. Esophagectomy (HR 0.50, 95% CI 0.44 to 0.56) and systemic therapy (HR 0.40, 95% CI 0.37 to 0.43) were associated with decreased risk of all-cause mortality. Patients undergoing esophagectomy had higher rates of 5-year OS (27.4% vs 13.2%, p < 0.0001) and longer median OS (24.71 vs 10.09 months, p < 0.0001). Among cT4b patients, those who underwent esophagectomy had higher rates of 5-year OS (24.5% vs 12.3%, p < 0.0001) and longer median OS (25.53 vs 11.01 months, p < 0.0001). CONCLUSIONS: In cT4 esophageal adenocarcinoma, esophagectomy is associated with improved rates of 5-year OS compared with nonsurgical treatment.

Does commission on cancer (CoC) accreditation mitigate the effect of care fragmentation on clinical outcome in localized rectal cancer?

BACKGROUND: Studies of fragmented care (FC) in rectal cancer have not adjusted for indicators of hospital quality and may misrepresent the effects of FC. METHODS: We queried the National Cancer Database to identify patients undergoing care for clinical stage II and III rectal adenocarcinoma between 2006 and 2019. Those undergoing FC were sub-categorized based on whether (FC CoC) or not (FC non-CoC) they received systemic therapy at CoC accredited facilities. RESULTS: 44,339 patients met inclusion criteria; 23,921 (54 â€‹%) underwent FC, 16,929 (71 â€‹%) FC non-CoC. Differences in utilization of neoadjuvant therapy (92.3 â€‹% vs 89.7 â€‹% vs 89.5 â€‹%, p â€‹< â€‹0.01) and 5-year overall survival (76.1 vs 75.5 vs 74.1 %, p â€‹< â€‹0.01) between treatment cohorts were marginal. CONCLUSION: In patients undergoing multimodality therapy for rectal cancer, care fragmentation is not associated with long-term clinical outcome. Decisions regarding where these patients go for systemic therapy may be safely made on the basis of ease of access.