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1.
Cell Death Dis ; 15(6): 403, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858387

ABSTRACT

Necroptosis is an inflammatory form of cell suicide that critically depends on the kinase activity of Receptor Interacting Protein Kinase 3 (RIPK3). Previous studies showed that immunization with necroptotic cells conferred protection against subsequent tumor challenge. Since RIPK3 can also promote apoptosis and NF-κB-dependent inflammation, it remains difficult to determine the contribution of necroptosis-associated release of damage-associated molecular patterns (DAMPs) in anti-tumor immunity. Here, we describe a system that allows us to selectively induce RIPK3-dependent necroptosis or apoptosis with minimal NF-κB-dependent inflammatory cytokine expression. In a syngeneic tumor challenge model, immunization with necroptotic cells conferred superior protection against subsequent tumor challenge. Surprisingly, this protective effect required CD4+ T cells rather than CD8+ T cells and is dependent on host type I interferon signaling. Our results provide evidence that death-dependent type I interferon production following necroptosis is sufficient to elicit protective anti-tumor immunity.


Subject(s)
Necroptosis , Receptor-Interacting Protein Serine-Threonine Kinases , Necroptosis/immunology , Animals , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Mice , Mice, Inbred C57BL , Interferon Type I/metabolism , CD8-Positive T-Lymphocytes/immunology , Signal Transduction , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Neoplasms/immunology , Neoplasms/pathology , Humans , NF-kappa B/metabolism , Cell Line, Tumor , Apoptosis/drug effects
2.
Ann Thorac Surg ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38615977

ABSTRACT

In 1945, the Welsh surgeon Ivor Lewis first reported performing the resection of a midesophageal tumor through a combined approach involving the abdomen and right chest. Although his technique was initially rebuffed by the preeminent esophageal surgeons of the time, it quickly became the standard approach for cancers of the midesophagus. Here we review the development and early dissemination of Lewis' operation using the case of the American actor Humphrey Bogart, who underwent an Ivor Lewis esophagectomy for esophageal cancer in 1956.

3.
Glob Chang Biol ; 30(4): e17257, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38572701

ABSTRACT

Countries are expanding marine protected area (MPA) networks to mitigate fisheries declines and support marine biodiversity. However, MPA impact evaluations typically assess total fish biomass. Here, we examine how fish biomass disaggregated by adult and juvenile life stages responds to environmental drivers, including sea surface temperature (SST) anomalies and human footprint, and multiple management types at 139 reef sites in the Mesoamerican Reef (MAR) region. We found that total fish biomass generally appears stable across the region from 2006 to 2018, with limited rebuilding of fish stocks in MPAs. However, the metric of total fish biomass masked changes in fish community structure, with lower adult than juvenile fish biomass at northern sites, and adult:juvenile ratios closer to 1:1 at southern sites. These shifts were associated with different responses of juvenile and adult fish to environmental drivers and management. Juvenile fish biomass increased at sites with high larval connectivity and coral cover, whereas adult fish biomass decreased at sites with greater human footprint and SST anomalies. Adult fish biomass decreased primarily in Honduran general use zones, which suggests insufficient protection for adult fish in the southern MAR. There was a north-south gradient in management and environmental drivers, with lower coverage of fully protected areas and higher SST anomalies and coastal development in the south that together may undermine the maintenance of adult fish biomass in the southern MAR. Accounting for the interplay between environmental drivers and management in the design of MPAs is critical for increasing fish biomass across life history stages.


Los países están ampliando las redes de áreas marinas protegidas (AMP) para mitigar la disminución de las pesquerías y apoyar la biodiversidad marina. Sin embargo, las evaluaciones de impacto de las AMP típicamente estudian la biomasa total de peces. Aquí, examinamos cómo la biomasa de peces desagregada por etapas de vida adultas y juveniles responde a factores ambientales como anomalías de la temperatura superficial del mar (SST) e impacto humano, y múltiples tipos de manejo en 139 sitios de arrecifes en el sistema arrecifal mesoamericano (SAM). Encontramos que la biomasa total de peces en general parece estable en toda la región entre 2006 y 2018, con una recuperación limitada de las poblaciones de peces en las AMP. Sin embargo, la métrica de biomasa total de peces enmascaró los cambios en la estructura de la comunidad de peces, con una biomasa de peces adultos más baja que juveniles en los sitios del norte, y proporciones adulto:juvenil más cercana a 1:1 en los sitios del sur. Estos cambios fueron asociados con diferentes respuestas de peces juveniles y adultos a variables ambientales y de manejo. La biomasa de peces juveniles aumentó en sitios con alta conectividad larvaria y cobertura coralina, mientras que la biomasa de peces adultos disminuyó en sitios con mayor impacto humano y anomalías en la SST. La biomasa de peces adultos disminuyó principalmente en las zonas de uso general (GUZ) hondureñas, lo cual sugiere una protección insuficiente para peces adultos en el sur del SAM. Hubo un gradiente norte­sur en el manejo y los factores ambientales, con menor cobertura de áreas totalmente protegidas y mayores anomalías de SST y desarrollo costero en el sur. En conjunto esto puede degradar el mantenimiento de la biomasa de peces adultos en el sur del SAM. La interacción entre factores ambientales y el manejo en el diseño de las AMP es fundamental para aumentar la biomasa de peces en todas las etapas del ciclo de vida.


Subject(s)
Anthozoa , Ecosystem , Animals , Humans , Coral Reefs , Conservation of Natural Resources , Biomass , Fishes/physiology , Fisheries
5.
Sci Total Environ ; 857(Pt 3): 159603, 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36272474

ABSTRACT

As climate change alters the global environment, it is critical to understand the relationship between shifting climate suitability and species distributions. Key questions include whether observed changes in population abundance are aligned with the velocity and direction of shifts predicted by climate suitability models and if the responses are consistent among species with similar ecological traits. We examined the direction and velocity of the observed abundance-based distribution centroids compared with the model-predicted bioclimatic distribution centroids of 250 bird species across the United States from 1969 to 2011. We hypothesized that there is a significant positive correlation in both direction and velocity between the observed and the modeled shifts. We then tested five additional hypotheses that predicted differential shifting velocity based on ecological adaptability and climate change exposure. Contrary to our hypotheses, we found large differences between the observed and modeled shifts among all studied bird species and within specific ecological guilds. However, temperate migrants and habitat generalist species tended to have higher velocity of observed shifts than other species. Neotropical migratory and wetland birds also had significantly different observed velocities than their counterparts, which may be due to their climate change exposure. The velocity based on modeled bioclimatic suitability did not exhibit significant differences among most guilds. Boreal forest birds were the only guild with significantly faster modeled-shifts than the other groups, suggesting an elevated conservation risk for high latitude and altitude species. The highly idiosyncratic species responses to climate and the mismatch between shifts in modeled and observed distribution centroids highlight the challenge of predicting species distribution change based solely on climate suitability and the importance of non-climatic factors traits in shaping species distributions.


Subject(s)
Birds , Climate Change , Animals , Animal Distribution , Birds/physiology , Ecosystem , North America
6.
Res Sq ; 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38196632

ABSTRACT

Necroptosis is an inflammatory form of cell suicide that critically depends on the kinase activity of Receptor Interacting Protein Kinase 3 (RIPK3). Previous studies showed that immunization with necroptotic cells conferred protection against subsequent tumor challenge. Since RIPK3 can also promote apoptosis and NF-κB-dependent inflammation, it remains difficult to determine the contribution of necroptosis-associated release of damage-associated molecular patterns (DAMPs) in anti-tumor immunity. Here, we describe a system that allows us to selectively induce RIPK3-dependent necroptosis or apoptosis with minimal NF-κB-dependent inflammatory cytokine expression. In a syngeneic tumor challenge model, immunization with necroptotic cells conferred superior protection against subsequent tumor challenge. Surprisingly, this protective effect required CD4+ T cells rather than CD8+ T cells and is dependent on host type I interferon signaling. Our results provide evidence that death-dependent type I interferon production following necroptosis is sufficient to elicit protective anti-tumor immunity.

7.
Transl Lung Cancer Res ; 11(7): 1453-1467, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35958338

ABSTRACT

Background: Evidence on the importance of lymph node (LN) dissection during resection for small cell lung cancer (SCLC) is scarce. This study sought to investigate the clinical impact of the extent of lymphadenectomy on the survival of patients with SCLC. Methods: Patients who underwent resection for primary SCLC between 2000 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) cancer registry. The patients were stratified based on the number of LNs dissected (0, 1-3, 4-11, and ≥12) via an X-Tile software analysis, and lung cancer-specific survival (LCSS) and overall survival (OS) were compared between these stratified groups using Kaplan-Meier curves. A propensity score-matched analysis and a Cox regression model were used to adjust for potential confounders. Results: A total of 1,883 patients with SCLC met our criteria and were enrolled in the study. The LCSS and OS analyses revealed that patients who underwent LN dissection during surgery had longer survival times significantly than patients who did not. Similarly, patients who underwent more extensive LN dissection (≥4 LNs) had longer survival times than those who underwent less extensive LN dissection (1-3 LNs). However, no significant increase in survival time was found for patients who underwent the dissection of ≥12 LNs compared to those who underwent the dissection of 4-11 LNs. These results were confirmed in our propensity-matched and Cox regression analyses. Conclusions: Our study revealed that patient survival after surgical resection for SCLC is associated with the number of dissected LNs, and the number of LNs for dissection ranges from 4 to 11 achieve the best survival outcome.

8.
Environ Evid ; 11(1): 15, 2022.
Article in English | MEDLINE | ID: mdl-35465308

ABSTRACT

Background: Natural climate solutions (NCS)-actions to conserve, restore, and modify natural and modified ecosystems to increase carbon storage or avoid greenhouse gas (GHG) emissions-are increasingly regarded as important pathways for climate change mitigation, while contributing to our global conservation efforts, overall planetary resilience, and sustainable development goals. Recently, projections posit that terrestrial-based NCS can potentially capture or avoid the emission of at least 11 Gt (gigatons) of carbon dioxide equivalent a year, or roughly encompassing one third of the emissions reductions needed to meet the Paris Climate Agreement goals by 2030. NCS interventions also purport to provide co-benefits such as improved productivity and livelihoods from sustainable natural resource management, protection of locally and culturally important natural areas, and downstream climate adaptation benefits. Attention on implementing NCS to address climate change across global and national agendas has grown-however, clear understanding of which types of NCS interventions have undergone substantial study versus those that require additional evidence is still lacking. This study aims to conduct a systematic map to collate and describe the current state, distribution, and methods used for evidence on the links between NCS interventions and climate change mitigation outcomes within tropical and sub-tropical terrestrial ecosystems. Results of this study can be used to inform program and policy design and highlight critical knowledge gaps where future evaluation, research, and syntheses are needed. Methods: To develop this systematic map, we will search two bibliographic databases (including 11 indices) and 67 organization websites, backward citation chase from 39 existing evidence syntheses, and solicit information from key informants. All searches will be conducted in English and encompass subtropical and tropical terrestrial ecosystems (forests, grasslands, mangroves, agricultural areas). Search results will be screened at title and abstract, and full text levels, recording both the number of excluded articles and reasons for exclusion. Key meta-data from included articles will be coded and reported in a narrative review that will summarize trends in the evidence base, assess gaps in knowledge, and provide insights for policy, practice, and research. The data from this systematic map will be made open access. Supplementary Information: The online version contains supplementary material available at 10.1186/s13750-022-00268-w.

9.
Transl Lung Cancer Res ; 11(3): 420-431, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35399567

ABSTRACT

Background: According to the latest the World Health Organization (WHO) classification in 2015, invasive mucinous adenocarcinoma (IMA) is defined as a new pathological subtype of lung adenocarcinoma (LUAD). However, whether this rare subtype of lung pathology has any difference in prognosis than conventional LUAD is debatable. Our study attempted to compare clinical characteristics and prognosis of IMA vs. noninvasive mucinous adenocarcinomas (NMA). Methods: A total of 1,857 patients with LUAD who underwent radical resection were screened from 2010 to 2015 at Zhejiang Cancer Hospital. Patients with pulmonary IMA were matched 1:1 by using propensity scores with LUAD adjusted for clinicopathological characteristics. After follow-up, overall survival (OS) and disease-free survival (DFS) were explored by Kaplan-Meier and Cox regression analyses. Forest plots were used for subgroup analyses. Results: Following screening, 499 patients with LUAD were enrolled, with 97 IMA and 402 NMA. Compared to NMA of the lung, IMA was proportionately lower in women (50.5% vs. 63.4%; P=0.026) and nonsmokers (P<0.001). IMA was also associated with earlier tumor stage I (68.0% vs. 55.5%; P=0.033) and lower frequency of upper lobe tumors compared to NMA (P=0.007). Following propensity score matching, 97 pairs were selected, among which we found that patients with pulmonary IMA had a longer OS than those with NMA (P=0.014). According to the subgroup analysis, improved OS in the IMA cohort versus the NMA cohort was observed across various factors, including the absence of lymphovascular invasion or perineural invasion. Conclusions: In this study, we found that resectable IMA patients had a better OS than NMA patients. This study contributes to the understanding of IMA in depth, but it needs to be validated through additional multicenter studies.

10.
Trends Biochem Sci ; 47(4): 342-351, 2022 04.
Article in English | MEDLINE | ID: mdl-34998669

ABSTRACT

Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 are signaling adaptors that critically regulate cell death and inflammation. Tumors have adapted to subvert RIPK-dependent cell death, suggesting that these processes have key roles in tumor regulation. Moreover, RIPK-driven cancer cell death might bolster durable antitumor immunity. By contrast, there are examples in which RIPKs induce inflammation and aid tumor progression. Furthermore, the RIPKs can exert their effects on tumor growth through regulating the activity of immune effectors in the tumor microenvironment, thus highlighting the context-dependent roles of RIPKs. Here, we review recent advances in the regulation of RIPK activity in tumors and immune cells and how these processes coordinate with each other to control tumorigenesis.


Subject(s)
Neoplasms , Receptor-Interacting Protein Serine-Threonine Kinases , Apoptosis , Cell Death/physiology , Humans , Immunity , Inflammation/metabolism , Necrosis , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Signal Transduction , Tumor Microenvironment
11.
Ann Thorac Surg ; 113(1): 366-371, 2022 01.
Article in English | MEDLINE | ID: mdl-34343472

ABSTRACT

In 1995, Dr Martin Dalton published a recounting of his involvement with the first human lung transplant in the Annals of Thoracic Surgery. As recalled in that account, the first lung transplant took place in the summer of 1963 in the context of another historical event, the assassination of Medgar Evers. This article is written in follow-up to Dalton's report in hopes of providing more insight into the events surrounding the assassination. This review will discuss the details of the assassination, attempted resuscitation, and the medical evidence presented in the trial of his assassin.


Subject(s)
Homicide/history , History, 20th Century , Homicide/legislation & jurisprudence , Mississippi , Wounds, Gunshot/history , Wounds, Gunshot/therapy
12.
Ann Surg ; 275(2): 348-355, 2022 02 01.
Article in English | MEDLINE | ID: mdl-32209899

ABSTRACT

OBJECTIVE: Determine whether adjuvant chemotherapy is associated with a survival benefit in high risk T2-4a, pathologically node-negative distal esophageal adenocarcinoma. SUMMARY OF BACKGROUND DATA: There is minimal literature to substantiate the NCCN guidelines recommending adjuvant therapy for patients with distal esophageal adenocarcinoma and no pathologic evidence of nodal disease. METHODS: The National Cancer Database was used to identify adult patients with pT2-4aN0M0 esophageal adenocarcinoma who underwent definitive surgery (2004-2015) and had characteristics considered high risk by the NCCN. Patients were stratified by receipt of adjuvant chemotherapy with or without radiation. The primary outcome was overall survival, which was evaluated using Kaplan-Meier and multivariable Cox Proportional Hazards models. A 1:1 propensity score-matched analysis was also performed to compare survival between the groups. RESULTS: Four hundred three patients met study criteria: 313 (78%) without adjuvant therapy and 90 who received adjuvant chemotherapy with or without radiation (22%). In both unadjusted and multivariable analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit compared to no adjuvant therapy. In a subgroup analysis of 335 patients without high risk features by NCCN criteria, adjuvant chemotherapy was not independently associated with a survival benefit. CONCLUSION: In this analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit in completely resected, pathologically node-negative distal esophageal adenocarcinoma, independent of presence of high risk characteristics. The risks and benefits of adjuvant therapy should be weighed before offering it to patients with completely resected pT2-4aN0M0 esophageal adenocarcinoma.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/mortality , Chemotherapy, Adjuvant , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/mortality , Esophagectomy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Survival Rate
13.
Ann Thorac Surg ; 113(3): 942-948, 2022 03.
Article in English | MEDLINE | ID: mdl-33857493

ABSTRACT

BACKGROUND: Endoscopic resection (ER) is the preferred treatment for superficial esophageal cancer; however, a safe time frame for performing ER has not been established. This study evaluated the period in which ER can be performed for patients with stage I esophageal adenocarcinoma without compromising outcomes. METHODS: The 2004-2015 National Cancer Database was used to identify patients with cT1 N0 M0 esophageal adenocarcinoma who underwent upfront ER. The primary outcome was overall survival, which was evaluated using Kaplan-Meier and multivariable Cox proportional hazards methods. The secondary outcome was rate of margin-positive resection, which was evaluated using a multivariable logistic regression. RESULTS: A total of 983 patients met study criteria. The median time from diagnosis to ER was 34 days (interquartile range, 5-70 days). Patients in the highest quartile of time to ER were more likely to be treated at a high-volume center and at a center different from that of diagnosis compared with those in the lowest quartile. Increasing time to ER was not independently associated with survival (adjusted hazard ratio per 10 days, 1.02; 95% confidence interval, 0.98-1.05; P = .32) or margin-positive resection (odds ratio per 10 days 1.01; 95% confidence interval, 0.96-1.06; P = .60). CONCLUSIONS: In this National Cancer Database analysis, increasing time to endoscopic resection, up to 180 days from diagnosis, was not associated with worsened survival or increased odds of margin-positive resection in patients with cT1 N0 M0 esophageal adenocarcinoma. Given these findings, patients may be afforded time to be seen in specialty centers without risk of tumor progression.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Adenocarcinoma/pathology , Esophagectomy/methods , Humans , Neoplasm Staging , Retrospective Studies , Treatment Outcome
14.
J Thorac Dis ; 13(11): 6587-6593, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34992837

ABSTRACT

Chronic lung allograft dysfunction remains the leading cause of long-term morbidity and mortality for lung transplant recipients. Lung retransplantation currently represents the only therapeutic option for patients for refractory allograft dysfunction. However, debate remains regarding both the efficacy and ethicality of lung retransplantation in light of the shortage of lung allografts. The aim of this review is to discuss the available literature on lung retransplantation in the current era. Through this we hope to provide insight into ideal patient selection, donor organ selection, surgical approaches, and future considerations within the field in order to improve outcomes and best address organ utilization while a waitlist continues to exist. Lung retransplantation in select patients can offer comparable survival outcomes to primary lung transplantation. However, several risk factors including retransplantation with the first year of primary transplantation, older age, poor functional status, and ICU level requirements prior to transplantation are associated with worsened outcomes. Donor organ selection considerations are comparable to those in primary lung transplantation. However, surgical approach is often impacted by dense pleural and mediastinal adhesions in the recipient which increase the complexity of the hilar dissection. The postoperative course is often more complex for patients undergoing retransplantation compared to those undergoing primary lung transplant as well. However, pending more data on long term outcomes in lung retransplantation and the potential impact of retransplant recipients on waitlist mortality, lung retransplantation should remain in use primarily for the treatment of chronic graft dysfunction in carefully selected patients.

15.
Mini Rev Med Chem ; 21(7): 792-802, 2021.
Article in English | MEDLINE | ID: mdl-33238842

ABSTRACT

CDATA[The inherited mutations and underexpression of BRCA1 in sporadic breast cancers resulting in the loss or functional inactivation of BRCA1 may contribute to a high risk of breast cancer. Recent researchers have identified small molecules (BRCA1 mimetics) that fit into a BRCA1 binding pocket within Estrogen Receptor alpha (ERα), mimic the ability of BRCA1 to inhibit ERα activity, and overcome antiestrogen resistance. Studies indicate that most of the BRCA1 breast cancer cases are associated with p53 mutations. It indicates that there is a potential connection between BRCA1 and p53. Most p53 mutations are missense point mutations that occur in the DNA-binding domain. Structural studies have demonstrated that mutant p53 core domain misfolding, especially p53-R175H, is reversible. Mutant p53 reactivation with a new class of zinc metallochaperones (ZMC) restores WT p53 structure and functions by restoring Zn2+ to Zn2+ deficient mutant p53. Considering the role of WT BRCA1 and reactivation of p53 in tumor cells, our hypothesis is to target both tumor suppressor proteins by a novel biomolecule (ZMC). Since both proteins are present in the same cell and are functionally inactive, this state may be a novel efficacious therapeutic regime for breast cancer therapy. In addition, we propose to use Albumin Nanovector (ANV) formulation for target drug release.


Subject(s)
Albumins/chemistry , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Molecular Chaperones/pharmacology , Nanoparticles/chemistry , Zinc/pharmacology , Antineoplastic Agents/chemistry , Cyclin D/antagonists & inhibitors , Cyclin D/metabolism , Drug Carriers/chemistry , Estrogen Receptor alpha/antagonists & inhibitors , Estrogen Receptor alpha/metabolism , Female , Humans , Molecular Chaperones/chemistry , Signal Transduction/drug effects , Tumor Suppressor Protein p53/antagonists & inhibitors , Tumor Suppressor Protein p53/metabolism , Zinc/chemistry
16.
Ecol Lett ; 23(9): 1404-1420, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32537896

ABSTRACT

Agriculture and development transform forest ecosystems to human-modified landscapes. Decades of research in ecology have generated myriad concepts for the appropriate management of these landscapes. Yet, these concepts are often contradictory and apply at different spatial scales, making the design of biodiversity-friendly landscapes challenging. Here, we combine concepts with empirical support to design optimal landscape scenarios for forest-dwelling species. The supported concepts indicate that appropriately sized landscapes should contain ≥ 40% forest cover, although higher percentages are likely needed in the tropics. Forest cover should be configured with c. 10% in a very large forest patch, and the remaining 30% in many evenly dispersed smaller patches and semi-natural treed elements (e.g. vegetation corridors). Importantly, the patches should be embedded in a high-quality matrix. The proposed landscape scenarios represent an optimal compromise between delivery of goods and services to humans and preserving most forest wildlife, and can therefore guide forest preservation and restoration strategies.


Subject(s)
Conservation of Natural Resources , Ecosystem , Biodiversity , Forests , Humans , Trees
17.
Ann Thorac Surg ; 110(6): 1854-1860, 2020 12.
Article in English | MEDLINE | ID: mdl-32544452

ABSTRACT

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend surgery for limited stage small cell lung cancer (SCLC). However, there is no literature on minimum acceptable lymph node retrieval in surgery for SCLC. METHODS: The National Cancer Database was queried for adult patients undergoing lobectomy for limited stage (cT1-2N0M0) SCLC from 2004 to 2015. Patients with unknown survival, staging, or nodal assessment, and patients who received neoadjuvant therapy were excluded. The number of lymph nodes assessed was studied both as a continuous variable and as a categoric variable stratified into distribution quartiles. The primary outcome was overall survival and the secondary outcome was pathologic nodal upstaging. RESULTS: A total of 1051 patients met study criteria. In multivariable analysis, only a retrieval of eight to 12 nodes was associated with a significant survival benefit (hazard ratio 0.73; 95% confidence interval, 0.56 to 0.98). However, when modeled as a continuous variable, there was no association between number of nodes assessed and survival (hazard ratio 1.00; 95% confidence interval, 0.98 to 1.02). The overall rate of pathologic nodal upstaging was 19%. Modeled as a continuous variable, more than seven lymph nodes assessed at time of resection was significantly associated with nodal upstaging in multivariable regression (odds ratio 1.03; 95% confidence interval, 1.01 to 1.06). CONCLUSIONS: In this study, there was no clear difference in survival based on increasing the number of lymph nodes assessed during lobectomy for limited stage SCLC. However, the number of retrieved lymph nodes was associated with pathologic nodal upstaging. Therefore, patients may benefit from retrieval of more than seven lymph nodes during lobectomy for SCLC.


Subject(s)
Lung Neoplasms/pathology , Lung Neoplasms/surgery , Lymph Node Excision , Pneumonectomy , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/surgery , Aged , Databases, Factual , Female , Humans , Lung Neoplasms/mortality , Lymph Nodes , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Small Cell Lung Carcinoma/mortality , Survival Rate , Treatment Outcome
18.
Adv Neurobiol ; 24: 469-479, 2020.
Article in English | MEDLINE | ID: mdl-32006368

ABSTRACT

Autism spectrum disorder (ASD) is an inherited neurodevelopmental disorder of social communication and restricted, repetitive behaviors. Much remains unknown about their mechanisms of action and physiological effects. In recent years, there has been a growing interest in nutritional diets, which can be used as a form of therapeutic intervention for ASD with a recent increase in the research being carried out in this field. Selective nutrition therapy for ASD and brain function shows improvement in behavioral changes and reduction in malnutrition seemingly associated with the allergies or food intolerances to gluten. Therefore, a gluten-free diet has yielded positive outcomes giving hope in developing therapy for ASD.


Subject(s)
Autism Spectrum Disorder/diet therapy , Autism Spectrum Disorder/immunology , Diet, Gluten-Free , Glutens/adverse effects , Glutens/immunology , Autism Spectrum Disorder/physiopathology , Autism Spectrum Disorder/psychology , Glutens/metabolism , Humans , Wheat Hypersensitivity/immunology , Wheat Hypersensitivity/metabolism
19.
J Thorac Cardiovasc Surg ; 159(4): 1616-1623, 2020 04.
Article in English | MEDLINE | ID: mdl-31836182

ABSTRACT

Lung cancer continues to be a leading cause of cancer-related death worldwide. Despite tremendous advances in surgical technique, chemotherapy regimens, radiation, and targeted therapies, survival is <50% at 5 years. Immunotherapy, specifically immune checkpoint inhibitors (ICIs), demonstrates promise as a solution to this clinical problem. Several agents have been Food and Drug Administration-approved for locally advanced and metastatic non-small cell lung cancer (NSCLC). Further studies are now exploring the use of these agents in the neoadjuvant and adjuvant settings. Although ICIs have demonstrated meaningful efficacy in NSCLC and other advanced malignancies, they are not without adverse toxicities. Furthermore, there are minimal data on their use in the perioperative period. Here we discuss the current domain of ICIs and their surgical implications in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Immunotherapy , Lung Neoplasms/therapy , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung Neoplasms/immunology , Lung Neoplasms/pathology
20.
Conserv Physiol ; 7(1): coz054, 2019.
Article in English | MEDLINE | ID: mdl-31452893

ABSTRACT

Sea-level rise, drought and water diversion can all lead to rapid salinization of freshwater habitats, especially in coastal areas. Increased water salinities can in turn alter the geographic distribution and ecology of freshwater species including turtles. The physiological consequences of salinization for freshwater turtles, however, are poorly known. Here, we compared the osmoregulatory response of two geographically separate populations of the freshwater Western Pond Turtle (Actinemys marmorata)-a species declining across its range in western North America-to three constant salinities: 0.4 ppt, 10 ppt and 15 ppt over 2 weeks. We found that turtles from a coastal estuarine marsh population regulated their plasma osmolality at lower levels than their conspecifics from an inland freshwater creek population 45 km away. Plasma osmolalities were consistently lower in estuarine marsh turtles than the freshwater creek turtles over the entire 2-week exposure to 10 ppt and 15 ppt water. Furthermore, estuarine marsh turtles maintained plasma osmolalities within 1 SD of their mean field osmolalities over the 2-week exposure, whereas freshwater creek turtles exceeded their field values within the first few days after exposure to elevated salinities. However, individuals from both populations exhibited body mass loss in 15 ppt water, with significantly greater loss in estuarine turtles. We speculate that the greater ability to osmoregulate by the estuarine marsh turtles may be explained by their reduced feeding and drinking in elevated salinities that was not exhibited by the freshwater creek population. However, due to mass loss in both populations, physiological and behavioural responses exhibited by estuarine marsh turtles may only be effective adaptations for short-term exposures to elevated salinities, such as those from tides and when traversing saline habitats, and are unlikely to be effective for long-term exposure to elevated salinity as is expected under sea-level rise.

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