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1.
J Surg Res ; 300: 287-297, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38833755

RESUMO

INTRODUCTION: Although outcome disparities by race have been identified in colorectal cancer, these patterns are challenging to explain using variables that are commonly available in databases. In a single institution serving a diverse community, length of stay (LOS) varies by race following elective oncologic colectomy. We investigated previously unexplored variables that may explain the relationship between race and LOS following elective resection of colorectal neoplasms. METHODS: Retrospective, single institution cohort study from January 2015 to December 2020 for adult patients undergoing elective colorectal cancer resections. Baseline demographic variables and intraoperative factors were analyzed for changes in LOS following elective colorectal resection. Additional retrospective chart review was carried out to determine household member composition and distance from home to hospital. Bivariate analysis was conducted to determine which variables should be included in multivariable analyses. All analyses were conducted using SAS Academic. RESULTS: Most patients (n = 383) were Asian (40%), Black (12%), or Hispanic (26%). Race and LOS were associated with age (P = 0.001 and P < 0.001 for race and LOS, respectively), American Society of Anesthesiologists class (P = 0.004 and P < 0.001), enhanced recovery after surgery protocols (P = 0.006 and P < 0.001), household members (P = 0.009 and P = 0.002), and discharge disposition (P = 0.049 and P < 0.001). In multivariable analysis, household members (P = 0.021) independently remained associated with LOS after controlling for race (P = 0.008) and discharge disposition (P < 0.001). CONCLUSIONS: Household member composition varies with LOS, suggesting that level of support at home may influence decisions regarding discharge disposition, which lead to differences in LOS.

2.
Surg Endosc ; 38(6): 2947-2963, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38700549

RESUMO

BACKGROUND: When pregnant patients present with nonobstetric pathology, the physicians caring for them may be uncertain about the optimal management strategy. The aim of this guideline is to develop evidence-based recommendations for pregnant patients presenting with common surgical pathologies including appendicitis, biliary disease, and inflammatory bowel disease (IBD). METHODS: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee convened a working group to address these issues. The group generated five key questions and completed a systematic review and meta-analysis of the literature. An expert panel then met to form evidence-based recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Expert opinion was utilized when the available evidence was deemed insufficient. RESULTS: The expert panel agreed on ten recommendations addressing the management of appendicitis, biliary disease, and IBD during pregnancy. CONCLUSIONS: Conditional recommendations were made in favor of appendectomy over nonoperative treatment of appendicitis, laparoscopic appendectomy over open appendectomy, and laparoscopic cholecystectomy over nonoperative treatment of biliary disease and acute cholecystitis specifically. Based on expert opinion, the panel also suggested either operative or nonoperative treatment of biliary diseases other than acute cholecystitis in the third trimester, endoscopic retrograde cholangiopancreatography rather than common bile duct exploration for symptomatic choledocholithiasis, applying the same criteria for emergent surgical intervention in pregnant and non-pregnant IBD patients, utilizing an open rather than minimally invasive approach for pregnant patients requiring emergent surgical treatment of IBD, and managing pregnant patients with active IBD flares in a multidisciplinary fashion at centers with IBD expertise.


Assuntos
Apendicectomia , Apendicite , Doenças Inflamatórias Intestinais , Laparoscopia , Complicações na Gravidez , Humanos , Gravidez , Feminino , Complicações na Gravidez/cirurgia , Complicações na Gravidez/terapia , Laparoscopia/métodos , Apendicite/cirurgia , Doenças Inflamatórias Intestinais/cirurgia , Apendicectomia/métodos , Doenças Biliares/cirurgia
3.
J Gastrointest Surg ; 28(5): 662-666, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38704203

RESUMO

BACKGROUND: This study aimed to determine the effect of Enhanced Recovery After Surgery (ERAS) protocols on the weekend effect after elective colectomies. METHODS: This was a retrospective study on all elective colorectal surgeries at a single institution in New York City between January 1, 2015, and December 31, 2020. The length of stay (LOS) by day of the week of surgery and the effect of ERAS using univariable and multivariable analyses were compared. RESULTS: A total of 605 patients were included in the study. Of note, 41 cases were performed on Mondays, 197 cases were performed on Tuesdays, 45 cases were performed on Wednesdays, 187 cases were performed on Thursdays, and 135 cases were performed on Fridays. Univariate analysis showed that, for patients who did not undergo ERAS, Monday and Tuesday were significantly associated with decreased LOS (P < .001). For patients who underwent ERAS, there was no statistically significant difference in LOS (P = .06) when operated on early in the week vs later. After controlling for age, race/ethnicity, comorbidities, complications, functional health status, operation type, duration of surgery, presence of ostomy, and albumin level, adhering to the ERAS protocol was significantly associated with a shorter LOS (P < .001). CONCLUSION: Our study demonstrated that ERAS can mitigate the weekend effect on LOS. ERAS protocols may provide more structure to the expected hospital course and allow patients to reach recovery milestones earlier, facilitating discharge even by covering teams.


Assuntos
Colectomia , Procedimentos Cirúrgicos Eletivos , Recuperação Pós-Cirúrgica Melhorada , Tempo de Internação , Humanos , Tempo de Internação/estatística & dados numéricos , Feminino , Estudos Retrospectivos , Masculino , Colectomia/métodos , Colectomia/efeitos adversos , Pessoa de Meia-Idade , Idoso , Fatores de Tempo , Cidade de Nova Iorque , Complicações Pós-Operatórias/epidemiologia
4.
J Immunol Methods ; 525: 113599, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38081407

RESUMO

Intestinal transplantation is the definitive treatment for intestinal failure. However, tissue rejection and graft-versus-host disease are relatively common complications, necessitating aggressive immunosuppression that can itself pose further complications. Tracking intraluminal markers in ileal effluent from standard ileostomies may present a noninvasive and sensitive way to detect developing pathology within the intestinal graft. This would be an improvement compared to current assessments, which are limited by poor sensitivity and specificity, contributing to under or over-immunosuppression, respectively, and by the need for invasive biopsies. Herein, we report an approach to reproducibly analyze ileal fluid obtained through stoma sampling for antimicrobial peptide/protein concentrations, reasoning that these molecules may provide an assessment of intestinal homeostasis and levels of intestinal inflammation over time. Concentrations of lysozyme (LYZ), myeloperoxidase (MPO), calprotectin (S100A8/A9) and ß-defensin 2 (DEFB2) were assessed using adaptations of commercially available enzyme-linked immunosorbent assays (ELISAs). The concentration of α-defensin 5 (DEFA5) was assessed using a newly developed sandwich ELISA. Our data support that with proper preparation of ileal effluent specimens, precise and replicable determination of antimicrobial peptide/protein concentrations can be achieved for each of these target molecules via ELISA. This approach may prove to be reliable as a clinically useful assessment of intestinal homeostasis over time for patients with ileostomies.


Assuntos
Peptídeos Antimicrobianos , alfa-Defensinas , Humanos , Intestinos , Ensaio de Imunoadsorção Enzimática , Biópsia
5.
Lancet Oncol ; 24(8): e344-e354, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37541280

RESUMO

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes. This Policy Review outlines existing knowledge gaps, collaborative opportunities, and specific recommendations regarding consensus priorities and future directions in brain metastases research. Achieving major advances in research will require enhanced coordination between the ongoing efforts of individual organisations and consortia. Importantly, the continual and active engagement of patients and patient advocates will be necessary to ensure that the directionality of all efforts reflects what is most meaningful in the context of patient care.


Assuntos
Pesquisa Biomédica , Neoplasias Encefálicas , Estados Unidos , Humanos , Qualidade de Vida , National Cancer Institute (U.S.) , Consenso , Neoplasias Encefálicas/terapia
7.
Curr Osteoporos Rep ; 21(2): 128-146, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36862360

RESUMO

PURPOSE OF REVIEW: To review the role of the immune cells and their interaction with cells found in gingiva, periodontal ligament, and bone that leads to net bone loss in periodontitis or bone remodeling in orthodontic tooth movement. RECENT FINDINGS: Periodontal disease is one of the most common oral diseases causing inflammation in the soft and hard tissues of the periodontium and is initiated by bacteria that induce a host response. Although the innate and adaptive immune response function cooperatively to prevent bacterial dissemination, they also play a major role in gingival inflammation and destruction of the connective tissue, periodontal ligament, and alveolar bone characteristic of periodontitis. The inflammatory response is triggered by bacteria or their products that bind to pattern recognition receptors that induce transcription factor activity to stimulate cytokine and chemokine expression. Epithelial, fibroblast/stromal, and resident leukocytes play a key role in initiating the host response and contribute to periodontal disease. Single-cell RNA-seq (scRNA-seq) experiments have added new insight into the roles of various cell types in the response to bacterial challenge. This response is modified by systemic conditions such as diabetes and smoking. In contrast to periodontitis, orthodontic tooth movement (OTM) is a sterile inflammatory response induced by mechanical force. Orthodontic force application stimulates acute inflammatory responses in the periodontal ligament and alveolar bone stimulated by cytokines and chemokines that produce bone resorption on the compression side. On the tension side, orthodontic forces induce the production of osteogenic factors, stimulating new bone formation. A number of different cell types, cytokines, and signaling/pathways are involved in this complex process. Inflammatory and mechanical force-induced bone remodeling involves bone resorption and bone formation. The interaction of leukocytes with host stromal cells and osteoblastic cells plays a key role in both initiating the inflammatory events as well as inducing a cellular cascade that results in remodeling in orthodontic tooth movement or in tissue destruction in periodontitis.


Assuntos
Reabsorção Óssea , Periodontite , Humanos , Osteoclastos/metabolismo , Técnicas de Movimentação Dentária , Reabsorção Óssea/metabolismo , Periodontite/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo
8.
J Surg Res ; 286: 74-84, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36774706

RESUMO

INTRODUCTION: Enhanced recovery after surgery (ERAS) colorectal programs have been shown to improve the length of stay (LOS) without increasing hospital resource utilization at academic centers worldwide. A multidisciplinary ERAS protocol that includes preoperative, intraoperative, and postoperative management guidelines was recently implemented at our urban, racially diverse, and academically affiliated community hospital. A delivery option was provided to reduce barriers to care. Given our unique patient population, the objective of our study was to determine if improvements in outcomes were reproducible in our hospital. METHODS: This is a retrospective study of patients undergoing elective colectomy at New York-Presbyterian Queens Hospital between January 1, 2015, and December 31, 2020. Patient outcomes were compared between surgeries performed under standard practice (all colectomies prior to April 2017) and those performed after the implementation of the ERAS protocol. Demographic and perioperative data were abstracted from a prospectively derived database used to submit data to the National Surgical Quality Improvement Program. Additional data were obtained from chart review. RESULTS: Six hundred five elective colectomies were performed by 12 surgeons (range 1-228 cases) during the study period. Of these, 22 were performed open (41% followed ERAS), 467 were performed laparoscopically (57% followed ERAS), and 116 were performed robotically (74% followed ERAS). The average patient age was 64 y. Of which, 55% were male; 34% were Asian, 27% were non-Hispanic Caucasian, 27% were Hispanic, and 11% were Black or African American (all P-values > 0.05 for ERAS versus non-ERAS). Average duration of procedure was longer in the ERAS group (262 min versus 243 min, P = 0.04), although when stratified by procedure type, this relationship held true only for laparoscopic procedures. Hospital LOS was significantly shorter in the ERAS group (4.3 versus 5.4 d, P < 0.001) and this relationship held true for procedures performed both laparoscopically (4.2 versus 5.3 d, P = 0.01) and robotically (4.1 versus 5.1 d, P = 0.04). Of the ERAS group, patients who opted for delivery of ERAS components (n = 205) had the shortest LOS when compared to patients who picked up components (n = 91) or opted out of ERAS (n = 309) (4.1 versus 4.4 versus 5.2 d, P = 0.003). No significant differences were found for 30-d mortality, 30-d readmission, wound infection, or other postoperative complications (all P-values > 0.05). CONCLUSIONS: Implementation of an ERAS protocol in an urban, diverse, academically affiliated community hospital is associated with reductions in LOS for colectomies performed both laparoscopically and robotically. Facilitating ERAS compliance with a delivery option was also associated with improvements in hospital LOS. Preoperative nutrition supplementation was not associated with outcomes. No differences in mortality, readmission rates, or rates of postoperative complications were found.


Assuntos
Neoplasias Colorretais , Recuperação Pós-Cirúrgica Melhorada , Humanos , Masculino , Feminino , Estudos Retrospectivos , Colectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tempo de Internação
9.
Surg Endosc ; 37(2): 781-806, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36529851

RESUMO

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common diseases in North America and globally. The aim of this guideline is to provide evidence-based recommendations regarding the most utilized and available endoscopic and surgical treatments for GERD. METHODS: Systematic literature reviews were conducted for 4 key questions regarding the surgical and endoscopic treatments for GERD in adults: preoperative evaluation, endoscopic vs surgical or medical treatment, complete vs partial fundoplication, and treatment for obesity (body mass index [BMI] ≥ 35 kg/m2) and concomitant GERD. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. RESULTS: The consensus provided 13 recommendations. Through the development of these evidence-based recommendations, an algorithm was proposed for aid in the treatment of GERD. Patients with typical symptoms should undergo upper endoscopy, manometry, and pH-testing; additional testing may be required for patients with atypical or extra-esophageal symptoms. Patients with normal or abnormal findings on manometry should consider undergoing partial fundoplication. Magnetic sphincter augmentation or fundoplication are appropriate surgical procedures for adults with GERD. For patients who wish to avoid surgery, the Stretta procedure and transoral incisionless fundoplication (TIF 2.0) were found to have better outcomes than proton pump inhibitors alone. Patients with concomitant obesity were recommended to undergo either gastric bypass or fundoplication, although patients with severe comorbid disease or BMI > 50 should undergo Roux-en-Y gastric bypass for the additional benefits that follow weight loss. CONCLUSION: Using the recommendations an algorithm was developed by this panel, so that physicians may better counsel their patients with GERD. There are certain patient factors that have been excluded from included studies/trials, and so these recommendations should not replace surgeon-patient decision making. Engaging in the identified research areas may improve future care for GERD patients.


Assuntos
Derivação Gástrica , Refluxo Gastroesofágico , Adulto , Humanos , Refluxo Gastroesofágico/cirurgia , Fundoplicatura/métodos , Endoscopia Gastrointestinal , Obesidade/complicações , Resultado do Tratamento
10.
Radiat Res ; 198(6): 625-631, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35976726

RESUMO

Preclinical studies inform and guide the development of novel treatment combination strategies that bridge the laboratory with the clinic. We aimed to evaluate approaches cancer researchers used to justify advancing new combinations of molecularly targeted agents and radiation treatment into early-phase human clinical trials. Unsolicited early phase clinical trial proposals submitted to the National Cancer Institute's Cancer Therapy Evaluation Program between January 2016 and July 2020 were curated to quantify key characteristics and proportion of preclinical data provided by trialists seeking to conduct molecularly targeted agent-radiation combination studies in cancer patients. These data elucidate the current landscape for how the rationale for a molecularly targeted agent-radiation combination therapy is supported by preclinical research and illustrate unique challenges faced in translation at the intersection of precision medicine and radiation oncology.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia
11.
Dermatol Ther (Heidelb) ; 12(8): 1885-1895, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35864377

RESUMO

INTRODUCTION: Achievement of remission in psoriatic arthritis is a key goal for patients and clinicians, yet definitions of remission may vary. Previous efforts have utilized multidomain measures such as minimal disease activity that assess the status of joints, skin, and function to determine current level of psoriatic arthritis (PsA) disease activity. The goal of this study is to identify factors associated with patient-reported psoriatic arthritis remission. METHODS: The National Psoriasis Foundation conducted a cross-sectional study using an online survey of a random stratified sample of 1570 individuals with psoriatic disease in the USA. Participants were asked about a provider diagnosis of psoriasis and/or psoriatic arthritis, comorbid conditions, and psoriatic arthritis impact and disease activity, and demographic questions. All participants reporting a physician-given diagnosis of psoriatic arthritis were asked if they felt their psoriatic arthritis was in remission ("Do you feel your psoriatic arthritis is in remission?" Yes/No/Unsure) and, if so, length of remission. Individuals with psoriasis and psoriatic arthritis reporting a body surface area impacted by psoriasis 3% or less were asked if they felt their psoriasis was in remission. Psoriatic arthritis disease activity and impact was assessed using the nine-question Psoriatic Arthritis Impact of Disease (PsAID-9) instrument and a global PsA-related quality of life question. PsAID-9 scores ≤ 4 were used to indicate acceptable disease state. Multivariate logistic regression was used to identify factors associated with patient-perceived PsA remission. RESULTS: Of 834 participants with PsA, including 76 (4.8%) with PsA without skin involvement ever, 144 (17.3%) felt their psoriatic arthritis was in remission, with an average remission duration of 43 months. Of those in remission, 116 (78.4%) reported currently using a treatment for their PsA, with most (75.7%) reporting using a biologic therapy for their PsA in the past 12 months. Multivariate logistic regression revealed that patient-perceived psoriatic arthritis remission was independently associated with experiencing acceptable disease state (PsAID-9 ≤ 4), perception of psoriasis remission, lower impact of PsA on global quality of life, and non-white race. Age, sex, body mass index, or biologic use in the last 12 months were not associated with patient-reported PsA remission. CONCLUSION: Overall, patient perception of PsA remission was most strongly associated with patient-reported psoriasis remission.

12.
J Psoriasis Psoriatic Arthritis ; 7(2): 79-92, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35757187

RESUMO

Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and co-morbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups.

13.
Surg Endosc ; 36(5): 2723-2733, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35237900

RESUMO

BACKGROUND: SARS-CoV-2 has changed global healthcare since the pandemic began in 2020. The safety of minimally invasive surgery (MIS) utilizing insufflation from the standpoint of safety to the operating room personnel is currently being explored. The aims of this guideline are to examine the existing evidence to provide guidance regarding MIS for the patient with, or suspecting of having, the SARS-CoV-2 as well as the healthcare team involved. METHODS: Systematic literature reviews were conducted for 2 key questions (KQ) regarding the safety of MIS in the setting of COVID-19 pandemic. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria. Evidence-based recommendations were formulated using a narrative synthesis of the literature by subject experts. Recommendations for future research were also proposed. RESULTS: In KQ1, a total of 1361 articles were reviewed, with 2 articles meeting inclusion. In KQ2, a total of 977 articles were reviewed, with 4 articles met inclusions criteria, of which 2 studies reported on the SARS-CoV2 virus specifically. Despite many publications in the field, very little well-controlled and unbiased data exist to inform the recommendations. Of that which is available, it shows that both laparoscopic and open operations in Covid-positive patients had similar rates of OR staff positivity rates; however, patients who underwent laparoscopic procedures had a lower perioperative mortality than open procedures. Also, SARS-CoV-2 particles have been detected in the surgical plume at laparoscopy. CONCLUSION: With demonstrated equivalence of operating room staff exposure, and noninferiority of laparoscopic access with respect to mortality, either laparoscopic or open approaches to abdominal operations may be used in patients with SARS-CoV-2. Measures should be employed for all laparoscopic or open cases to prevent exposure of operating room staff to the surgical plume, as virus can be present in this plume.


Assuntos
COVID-19 , Laparoscopia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Laparoscopia/métodos , Pandemias/prevenção & controle , RNA Viral , SARS-CoV-2
15.
Front Immunol ; 13: 835760, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309349

RESUMO

Early diagnosis of psoriatic arthritis (PSA) is important for successful therapeutic intervention but currently remains challenging due, in part, to the scarcity of non-invasive biomarkers. In this study, we performed single cell profiling of transcriptome and cell surface protein expression to compare the peripheral blood immunocyte populations of individuals with PSA, individuals with cutaneous psoriasis (PSO) alone, and healthy individuals. We identified genes and proteins differentially expressed between PSA, PSO, and healthy subjects across 30 immune cell types and observed that some cell types, as well as specific phenotypic subsets of cells, differed in abundance between these cohorts. Cell type-specific gene and protein expression differences between PSA, PSO, and healthy groups, along with 200 previously published genetic risk factors for PSA, were further used to perform machine learning classification, with the best models achieving AUROC ≥ 0.87 when either classifying subjects among the three groups or specifically distinguishing PSA from PSO. Our findings thus expand the repertoire of gene, protein, and cellular biomarkers relevant to PSA and demonstrate the utility of machine learning-based diagnostics for this disease.


Assuntos
Artrite Psoriásica , Psoríase , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/genética , Biomarcadores , Epitopos , Humanos , Aprendizado de Máquina , Psoríase/diagnóstico , Psoríase/genética , Transcriptoma
16.
Transl Lung Cancer Res ; 10(7): 3079-3092, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430349

RESUMO

BACKGROUND: Although most malignancies express cancer-testis antigens (CTA), immune responses to these proteins are limited in thoracic oncology patients. This trial was undertaken to examine if a cancer cell lysate vaccine could induce immunity to CTA, and to ascertain if metronomic cyclophosphamide and celecoxib enhances vaccine-induced immune responses. METHODS: Eleven patients with primary thoracic malignancies and 10 patients with extrathoracic neoplasms metastatic to the chest rendered NED by conventional therapies were randomized to receive H1299 lung cancer cell lysates (10 mg protein/vaccine) with Iscomatrix™ adjuvant via deep intradermal injection q 4 weeks ×6 with or without daily oral metronomic cyclophosphamide/celecoxib. The primary endpoint was serologic response to purified CTA assessed 1 month after the 6th vaccination. Secondary endpoints included assessment of the effects of cyclophosphamide and celecoxib on frequency and magnitude of vaccine-induced immune responses to CTA. Exploratory endpoints included evaluation of the effects of the vaccine regimens on peripheral immune subsets. Standard of care imaging studies were obtained at baseline and 1 month after the 3rd and 6th vaccinations. RESULTS: All patients exhibited local and systemic inflammatory responses lasting 72-96 hours following vaccinations. There were no dose limiting treatment related toxicities. Fourteen patients (67%) completed all six vaccinations. Eight of 14 patients (57%) exhibited serologic responses to NY-ESO-1. One patient developed antibodies to GAGE7; several patients exhibited reactivity to XAGE and MAGE-C2. Vaccine therapy decreased the percent of Tregs (P=0.0068), PD-1 expression on Tregs (P=0.0027), PD-L1 expression on CD14+ monocytes (P=0.0089), PD-L1 expression on classical monocytes (P=0.016), and PD-L1 expression on intermediate monocytes (P=0.0031). Cyclophosphamide/celecoxib did not appear to increase immune responses or enhance vaccine-induced alterations in peripheral immune subsets. CONCLUSIONS: H1299 lysate vaccines with Iscomatrix™ induce immune responses to CTA and modulate peripheral immune subsets in a manner that may enhance antitumor immunity in patients with thoracic malignancies.

17.
JNCI Cancer Spectr ; 5(4)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34350377

RESUMO

In a time of rapid advances in science and technology, the opportunities for radiation oncology are undergoing transformational change. The linkage between and understanding of the physical dose and induced biological perturbations are opening entirely new areas of application. The ability to define anatomic extent of disease and the elucidation of the biology of metastases has brought a key role for radiation oncology for treating metastatic disease. That radiation can stimulate and suppress subpopulations of the immune response makes radiation a key participant in cancer immunotherapy. Targeted radiopharmaceutical therapy delivers radiation systemically with radionuclides and carrier molecules selected for their physical, chemical, and biochemical properties. Radiation oncology usage of "big data" and machine learning and artificial intelligence adds the opportunity to markedly change the workflow for clinical practice while physically targeting and adapting radiation fields in real time. Future precision targeting requires multidimensional understanding of the imaging, underlying biology, and anatomical relationship among tissues for radiation as spatial and temporal "focused biology." Other means of energy delivery are available as are agents that can be activated by radiation with increasing ability to target treatments. With broad applicability of radiation in cancer treatment, radiation therapy is a necessity for effective cancer care, opening a career path for global health serving the medically underserved in geographically isolated populations as a substantial societal contribution addressing health disparities. Understanding risk and mitigation of radiation injury make it an important discipline for and beyond cancer care including energy policy, space exploration, national security, and global partnerships.


Assuntos
Inteligência Artificial/tendências , Neoplasias/radioterapia , Assistência Centrada no Paciente/tendências , Radioterapia (Especialidade)/tendências , Pesquisa/tendências , Big Data , Ensaios Clínicos como Assunto , Humanos , Hipertermia Induzida , Terapia por Captura de Nêutron/métodos , Assistência Centrada no Paciente/organização & administração , Fotoquimioterapia , Radioterapia (Especialidade)/organização & administração , Tolerância a Radiação , Radiobiologia/educação , Compostos Radiofarmacêuticos/uso terapêutico , Radioterapia/efeitos adversos , Radioterapia/métodos , Radioterapia/tendências , Eficiência Biológica Relativa , Pesquisa/organização & administração , Apoio à Pesquisa como Assunto
18.
Eur J Nucl Med Mol Imaging ; 49(1): 64-72, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34378064

RESUMO

BACKGROUND: Radiopharmaceutical targeted therapy (RPT) has been studied for decades; however, recent clinical trials demonstrating efficacy have helped renewed interest in the modality. METHODS: This article reviews National Cancer Institute (NCI)'s support of RPT through communication via workshops and interest groups, through funding extramural programs in academia and small business, and through intramural research, including preclinical and clinical studies. RESULTS: NCI has co-organized workshops and organized interest groups on RPT and RPT dosimetry to encourage the community and facilitate rigorous preclinical and clinical studies. NCI has been supporting RPT research through various mechanisms. Research has been funded through peer-reviewed NCI Research and Program Grants (RPG) and NCI Small Business Innovation Research (SBIR) Development Center, which funds small business-initiated projects, some of which have led to clinical trials. The NCI Cancer Therapy Evaluation Program (CTEP)'s Radiopharmaceutical Development Initiative supports RPT in NCI-funded clinical trials, including Imaging and Radiation Oncology Core (IROC) expertise in imaging QA and dosimetry procedures. Preclinical targeted a-emitter therapy (TAT) research at the NCI's intramural program is ongoing, building on foundational work dating back to the 1980s. Ongoing "bench-to-bedside" efforts leverage the unique infrastructure of the National Institutes of Health's (NIH) Clinical Center. CONCLUSION: Given the great potential of RPT, our goal is to continue to encourage its development that will generate the high-quality evidence needed to bring this multidisciplinary treatment to patients.


Assuntos
Neoplasias , Humanos , National Cancer Institute (U.S.) , Neoplasias/radioterapia , Radiometria , Compostos Radiofarmacêuticos , Estados Unidos
19.
Dermatol Ther (Heidelb) ; 11(3): 799-831, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33978917

RESUMO

Nail psoriasis has a prevalence that ranges from 10 to 82% and can significantly impact the quality of life of patients. Nail psoriasis is one of the most challenging areas to treat, and multiple therapies have been explored. Topical and injectable therapies are recommended for few-nail disease. Systemic therapies, including biologics, can be considered for patients with multiple and resistant nail disease, impaired quality of life, and severe skin and joint involvement, due to their long-term efficacy. Although outcome data are difficult to compare, interleukin (IL)-17 inhibitors may have superior short-term efficacy when compared to IL-23 inhibitors and tumor necrosis factor (TNF)-alpha inhibitors, although long-term efficacy is similar to TNF-alpha inhibitors. IL-23 inhibitors and TNF-alpha inhibitors have a similar efficacy for nail psoriasis.

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