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1.
Curr Opin Anaesthesiol ; 36(4): 399-406, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37338939

RESUMO

RECENT FINDINGS: Surgical procedures that involve general anesthesia are performed with either volatile anesthetics or propofol-based total intravenous anesthesia. Both techniques are safe and provide appropriate conditions for surgery. Despite being a well established anesthetic, the use of propofol-based total intravenous anesthesia (TIVA) remains low. Possible explanations include the perceived increase risk of awareness, lack of target controlled infusion devices, increased turnover time for device set up and individual preference. SUMMARY: There are some scenarios where patients could potentially benefit from propofol-based TIVA rather than a volatile anesthetic (e.g. postoperative nausea and vomiting) and some other clinical scenarios where the use of propofol-based anesthesia remains controversial since the strength of the evidence remains low. PURPOSE: In this review we will summarize the clinical evidence comparing the effect of propofol-based TIVA and volatile anesthetic on postoperative outcomes such as postoperative nausea and vomiting, postoperative pain, quality of recovery, postoperative cognitive dysfunction and cancer outcomes.


Assuntos
Anestésicos Inalatórios , Propofol , Humanos , Propofol/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Anestesia Intravenosa/efeitos adversos , Anestesia Intravenosa/métodos , Anestesia por Inalação/efeitos adversos , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos
2.
Br J Haematol ; 195(5): 743-747, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34544201

RESUMO

Low-affinity immunoglobulin gamma Fc region receptor III-B (FcγRIIIB) deficiency is present in ˜0·05% of the general population. Among our patients, FcγRIIIB deficiency was less frequent in those with immune-system disorders (one of 1815 patients, 0·05%) than in those with blood disorders (nine of 2147 patients, 0·42%, P = 0·023): mainly primary immune thrombocytopenia (4·34%), therapy related myeloid neoplasms (1·16%) and myelodysplastic syndrome with excess blasts (1·28%). Four of the nine (44·4%) patients with blood disorders were diagnosed with or quickly evolved to acute myeloid leukaemia (AML), suggesting that FcγRIIIB deficiency could be an adverse prognostic factor for progression to AML that should be confirmed in large multicentre studies.


Assuntos
Doenças Hematológicas/patologia , Doenças do Sistema Imunitário/patologia , Receptores de IgG/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Progressão da Doença , Feminino , Proteínas Ligadas por GPI/análise , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Síndromes Mielodisplásicas/patologia , Neutrófilos/patologia , Púrpura Trombocitopênica Idiopática/patologia , Adulto Jovem
3.
Int J Mol Sci ; 22(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918790

RESUMO

Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (p < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% p < 0.0001) for MGUS, 82.5%/64.7% (p < 0.05) for SMM, and 62.3%/47.0% (p < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (p < 0.0001), 74.2%/50.4% (p < 0.0001), and 35.3%/20.0% (p = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, p < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PAhigh, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PAhigh at higher risk of progression and death.


Assuntos
Apoptose , Biomarcadores Tumorais , Neoplasias de Plasmócitos/diagnóstico , Neoplasias de Plasmócitos/etiologia , Lesões Pré-Cancerosas , Idoso , Biópsia , Medula Óssea/patologia , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias de Plasmócitos/mortalidade , Neoplasias de Plasmócitos/terapia , Prognóstico , Curva ROC , Fatores de Risco , Avaliação de Sintomas
4.
Vertex ; 29(138): 133-138, 2018 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-30605186

RESUMO

Currently, obesity has become one of the greatest concerns of global health since it is associated with a signifcant increase in population morbidity and mortality. Specifcally for severe obesity (BMI> to 40) treatments that include bariatric surgeries have shown greater effcacy in the long term outcomes. This article presents the prevalence of psychiatric disorders observed in the pre-surgical assessment of 968 candidates from a multidisciplinary team of a public hospital in the city of Buenos Aires during the period 2006 to 2011. The 68% of the sample (n=656) corresponded to women from an age range of 19 to 69 years while 32% of de sample (n=312) corresponded to males from 18 to 72 years. The evaluation was carried out in the form of a semi-structured clinical interview that resulted in a high prevalence of psychiatric disorders: 46.5%. Of which eating disorders predominate (51%), affective disorders (36.2%) and anxiety disorders (10%), including in the latter the percentage of adjustment disorders. These results were contrasted with relevant studies from other countries. As a conclusion, the need for standardized measurement methods is evident. So is the importance of specialized psychiatric approaches within the framework of surgical treatment teams for obesity, given that the most prevalent psychiatric pathologies are not considered an impediment to surgeries if they are adequately treated. The role of the mental health specialist is of vital importance for the improvement of the treatment results, so it should not be reduced to assess the aptitude of the candidate for surgery.


Assuntos
Cirurgia Bariátrica , Transtornos Mentais , Obesidade Mórbida , Adulto , Idoso , Feminino , Hospitais Públicos , Humanos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Transtornos do Humor , Obesidade Mórbida/psicologia , Obesidade Mórbida/cirurgia , Prevalência , Adulto Jovem
5.
World J Surg Oncol ; 15(1): 152, 2017 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-28807031

RESUMO

BACKGROUND: The magnitude of the perioperative inflammatory response plays a role in surgical outcomes. However, few studies have explored the mechanisms of the resolution of inflammation in the context of surgery. Here, we described the temporal kinetics of interleukin-6, cortisol, lipoxin A4, and resolvin D in patients who underwent oncologic liver resections. METHODS: All patients gave written informed consent. Demographic and perioperative surgical data were collected, along with blood samples, before surgery and on the mornings of postoperative days 1, 3, and 5. Interleukin-6, cortisol, lipoxin-A4, and resolvin D were measured in plasma. A P value < 0.05 was considered statistically significant. RESULTS: Forty-one patients were included in the study. Liver resection for colorectal metastatic disease was the most commonly performed surgery. The plasma concentrations of interleukin-6 were highest on day 1 after surgery and remained higher than the baseline up to postoperative day 1. Postoperative complications occurred in 14 (24%) patients. Cortisol concentrations spiked on postoperative day 1. The concentrations of lipoxin A4 and resolvin D were lowest on day 1 after surgery. CONCLUSIONS: The inflammatory response associated with hepatobiliary surgery is associated with low circulating concentrations of lipoxin A4 and resolvin D that mirror, in an opposite manner, the kinetics of interleukin 6 and cortisol. TRIAL REGISTRATION: NCT01438476.


Assuntos
Anti-Inflamatórios/sangue , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Neoplasias Colorretais/cirurgia , Hepatectomia/efeitos adversos , Inflamação/sangue , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/sangue , Idoso , Neoplasias Colorretais/patologia , Ácidos Docosa-Hexaenoicos/sangue , Feminino , Humanos , Hidrocortisona/sangue , Inflamação/etiologia , Interleucina-6/sangue , Lipoxinas/sangue , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Complicações Pós-Operatórias/etiologia , Prognóstico , Fatores de Tempo , Resultado do Tratamento
6.
J Surg Res ; 194(1): 185-93, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25475022

RESUMO

BACKGROUND: The cytotoxic activity and count of natural killer (NK) cells appear to be reduced after surgery; however, it is unknown whether the magnitude of this immune suppression is similar among different types of oncological surgery. In this study, we compared the innate immune function of patients undergoing three different oncological surgeries. METHODS: We compared the number and function of NK cells obtained from patients who had undergone mastectomies (n = 17), thoracotomies (n = 21), or liver resections for cancer (n = 22). Cytotoxicity assays were performed to measure the function of NK cells. We also determined the plasma concentrations of interleukins (IL) 2 and 4, interferon-γ, granzyme B, perforin, soluble major histocompatibility complex class I-related chain A, and epinephrine, both before and 24 h after surgery. Differences in immunologic parameters were compared preoperatively and postoperatively and by type of surgery. P values <0.05 were considered statistically significant. RESULTS: The preoperative NK cell count differed statistically (P < 0.006) among all three types of surgeries; however, within surgery postoperative counts and changes compared with baseline did not. The postoperative function of NK cells was similar among types of surgeries, but was significantly reduced compared with preoperative levels (mastectomy P < 0.0001, thoracotomy P = 0.001, and liver resections P = 0.002). We observed a significant increase in the postoperative plasma concentrations of epinephrine, whereas the concentrations of major histocompatibility class I polypeptide-related sequence A and the IL-2 and/or IL-4 ratio remained unchanged before and after surgery. CONCLUSIONS: The magnitude of innate immune suppression is similar among different oncological procedures. More studies are needed to better understand this complex phenomenon.


Assuntos
Neoplasias da Mama/cirurgia , Neoplasias Colorretais/cirurgia , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Neoplasias da Mama/imunologia , Neoplasias Colorretais/imunologia , Citocinas/fisiologia , Epinefrina/sangue , Feminino , Humanos , Imunidade Inata , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta/fisiologia
9.
Diabetes Ther ; 15(4): 749-761, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38378924

RESUMO

It is a well-evidenced fact that diet significantly impacts type 2 diabetes mellitus (T2DM) prevention and management. However, dietary responses vary among different populations, necessitating personalized recommendations. Substantial evidence supports the role of diet in T2DM remission, particularly low-energy or low-carbohydrate diets that facilitate weight loss, enhance glycemic control, and achieve remission. This review aims to comprehensively analyze and compare personalized nutritional interventions with non-personalized approaches in T2DM remission. We conducted a literature search using the Academy of Nutrition and Dietetics guidelines, focusing on clinical and observational trials published within the past decade. We present the strengths and drawbacks of incorporating personalized nutrition into practice, along with the areas for research in implementing personalized interventions, such as cost-effectiveness and accessibility. The findings reveal consistently higher diabetes remission rates in personalized nutrition studies compared to non-personalized interventions.

10.
J Pain Res ; 16: 4181-4189, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38078017

RESUMO

Cancer-related pain is one of the most common and incapacitating symptoms for cancer patients. Cancer pain can be caused by diagnostic or therapeutic procedures, side effects and toxicity from therapy, or the cancer itself. Uncontrolled cancer-related pain is associated with inadequate quality of life and reduced functional status. Optimal pain management during the perioperative period requires a tailored approach. Interventions that are recommended for the management of acute surgical pain include regional anesthesia, local anesthetic infusions, non-opioid analgesics (ketamine, dexmedetomidine, lidocaine, and non-steroidal anti-inflammatory drugs), and opioids. Despite continued research efforts and advances in cancer treatment, opioids remain the most effective medication to treat moderate to severe cancer-related pain; however, their role has been changing significantly due to the opioid epidemic and opioid misuse. While pre-clinical and retrospective studies have shown a negative association between opioid use and cancer outcomes, randomized control trials have failed to confirm this association. The purpose of this review is to summarize the pharmacological management of acute cancer-related pain during the perioperative period with an emphasis on cancer recurrence.

11.
BJA Open ; 6: 100136, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37588172

RESUMO

Background: Postoperative acute kidney injury (AKI) is a common complication and is associated with increased hospital length of stay and 30 day all-cause mortality. Unfortunately, we have neither a defined strategy to prevent AKI nor an effective treatment. In vitro, animal, and human studies have suggested that dexmedetomidine may have a renoprotective effect. We conducted a retrospective cohort study to evaluate if intraoperative dexmedetomidine was associated with a reduced incidence of AKI. Methods: We collected data from 6625 patients who underwent major non-cardiothoracic cancer surgery. Before and after propensity score matching, we compared the incidence of postoperative AKI in patients who received intraoperative dexmedetomidine and those who did not. AKI was defined according to the Kidney Disease Improving Global Outcomes (creatinine alone values) criteria and calculated for postoperative Days 1, 2, and 3. Results: Twenty per cent (n=1301) of the patients received dexmedetomidine. The mean [standard deviation] administered dose was 78 [49.4] mcg. Patients treated with dexmedetomidine were matched to those who did not receive the drug. Patients receiving dexmedetomidine had a longer anaesthesia duration than the non-dexmedetomidine group. The incidence of AKI was not significantly different between the groups (dexmedetomidine 8% vs no dexmedetomidine 7%; P=0.333). The 30 day rates of infection, cardiovascular complications, or reoperation attributable to bleeding were higher in patients treated with dexmedetomidine. The 30 day mortality rate was not statistically different between the groups. Conclusions: The administration of dexmedetomidine during major non-cardiothoracic cancer surgery is not associated with a reduction in AKI within 72 h after surgery.

12.
Minerva Anestesiol ; 88(4): 300-307, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34636223

RESUMO

Opioids remain the most potent and predictable drug available for perioperative analgesia and moderate-to-severe cancer-related pain. However, their efficacy has been questioned in other clinical settings. Moreover, opioids are associated with a wide variety of dose-dependent adverse events, limiting their use. The indiscriminate prescription of opioids has fueled the so-called "opioid epidemic" in the United States and other developed countries. Thus, there has been a significant effort to develop strategies to curtail their unnecessary prescription. Here, we summarize the history, current trends, and new directions in perioperative opioid prescription in an unbiased manner.


Assuntos
Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/efeitos adversos , Humanos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Estados Unidos
13.
Pain Manag ; 12(2): 229-242, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34636651

RESUMO

Cancer-related pain is one of the most common and debilitating symptoms among cancer patients. Undertreated cancer-related pain interferes with daily activities and increases morbidity and mortality. While opioids continue to play an essential role in treating moderate to severe cancer-related pain, they are associated with many adverse effects including misuse. While preclinical and retrospective studies have shown a negative association between opioid use and cancer outcomes, randomized control trials demonstrate that opioid use does not influence cancer recurrence. Additionally, analgesics and adjuvants used for perioperatively or chronic pain control are unlikely to improve oncological outcomes. This article focuses on the pharmacological management of cancer-related pain and offers an overview regarding the use of these medications perioperatively and the cancer outcomes.


Assuntos
Neoplasias , Dor Pós-Operatória , Analgésicos/uso terapêutico , Analgésicos Opioides/efeitos adversos , Humanos , Neoplasias/complicações , Dor Pós-Operatória/tratamento farmacológico , Estudos Retrospectivos
14.
Front Oncol ; 12: 1062158, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36741691

RESUMO

In addition to attaining complete or near complete cytoreduction, the instillation of select heated chemotherapeutic agents into the abdominal cavity has offered a chance for cure or longer survival inpatients with peritoneal surface malignancies. While the heating of chemotherapeutic agents enhances cytotoxicity, the resulting systemic hyperthermia has been associated with an increased risk of severe hyperthermia and its associated complications. Factors that have been associated with an increased risk of severe hyperthermia include intraoperative blood transfusions and longer perfusion duration. However, the development of severe hyperthermia still remains largely unpredictable. Thus, at several institutions, cooling protocols are employed during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Cooling protocols for CRS-HIPEC are not standardized and may be associated with episodes of severe hyperthermia or alternatively hypothermia. In theory, excessive cooling could result in a decreased effectiveness of the intraperitoneal chemotherapeutic agents. This presumption has been supported by a recent study of 214 adults undergoing CRS-HIPEC, where failure to attain a temperature of 38° C at the end of chemo-perfusion was associated with worse survival. Although not statistically significant, failure to maintain a temperature of 38° C for at least 30 minutes was associated with worse survival. Although studies are limited in this regard, the importance of maintaining a steady state of temperature during the hyperthermic phase of intraperitoneal chemotherapy administration cannot be disregarded. The following article describes the processes and physiological mechanisms responsible for hyperthermia during CRS-HIPEC. The challenges associated with temperature management during CRS-HIPEC and methods to avoid severe hypothermia and hyperthermia are also described.

15.
Front Oncol ; 11: 788918, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956903

RESUMO

Despite advances in cancer treatments, surgery remains one of the most important therapies for solid tumors. Unfortunately, surgery promotes angiogenesis, shedding of cancer cells into the circulation and suppresses anti-tumor immunity. Together this increases the risk of tumor metastasis, accelerated growth of pre-existing micro-metastasis and cancer recurrence. It was theorized that regional anesthesia could influence long-term outcomes after cancer surgery, however new clinical evidence demonstrates that the anesthesia technique has little influence in oncologic outcomes. Several randomized controlled trials are in progress and may provide a better understanding on how volatile and intravenous hypnotics impact cancer progression. The purpose of this review is to summarize the effect of the anesthesia techniques on the immune system and tumor microenvironment (TME) as well as to summarize the clinical evidence of anesthesia techniques on cancer outcomes.

16.
Neurosci Lett ; 746: 135661, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33482308

RESUMO

Pain is a common and devastating symptom among cancer patients. It can be caused by the cancer itself or by certain therapies like surgery, radiation or chemotherapy. Opioids are the first line of treatment for moderate to severe cancer-related pain. Opioids alone or in combination with non-opioid analgesics and adjuvant medications are important components for pain management during the perioperative period for cancer patients. Opioids act on the µ-opioid receptor (MOR), which is expressed in cancer cells and non-malignant cells of the tumor microenvironment. Retrospective studies suggest an association between the expression of MOR in cancers and shorter survival. In addition, recent evidence suggests that opium use and prescription opioids can influence clinical oncological outcomes. In this review, we will summarize the clinical evidence regarding the effect of opioid administration and survival in patients with cancer as well as the current evidence involving MOR expression and cancer progression.


Assuntos
Analgésicos Opioides/efeitos adversos , Dor do Câncer/metabolismo , Medicina Baseada em Evidências/métodos , Neoplasias/metabolismo , Receptores Opioides mu/biossíntese , Microambiente Tumoral/fisiologia , Analgésicos Opioides/administração & dosagem , Animais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Dor do Câncer/diagnóstico , Dor do Câncer/tratamento farmacológico , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Manejo da Dor/efeitos adversos , Manejo da Dor/métodos , Prognóstico , Receptores Opioides mu/genética , Estudos Retrospectivos , Microambiente Tumoral/efeitos dos fármacos
17.
Am J Cancer Res ; 11(6): 2736-2753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249425

RESUMO

Standard risk stratification (sRisk) guides clinical management in monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) and multiple myeloma (MM). Nonetheless, clinical results are considerably heterogeneous among patients with similar risk status. Blood and bone marrow samples from 276 MGUS, 56 SMM and 242 MM in regular clinical practice were analyzed at diagnosis by flow cytometry. Higher levels of aberrant circulating plasma cells (cPC) (> 0.0035% of leukocytes), combined with albumin, beta2-microglobuline and lactate-dehydrogenase levels, offered minimally-invasive risk stratification (RcPC) with results comparable to sRisk. RcPC and sRisk 10-year progression-free-survival (10y-PFS) rates were: 93.8% vs. 95.1% for low-risk, 78.4% vs. 81.7% for intermediate-risk and 50.0% vs. 47.8% for high-risk MGUS; 58.3% vs. 57.8% low-risk, 44.4% vs. 45.8% intermediate-risk and 8.9% vs. 15.0% high-risk SMM; and 44.4% vs. 44.4% low-risk, 36.1% vs. 36.8% intermediate-risk, and 13.3% vs. 16.2% high-risk MM. Circulating-PC > 0.0035% vs. cPC<0.0035% was an independent prognostic factor for PFS (HR=4.389, P=1.2×10-15, Harrell C-statistic =0.7705±0.0190) and over-all survival (OS, HR=4.286, 2.3×10-9, Harrell C-statistic =0.8225±0.0197) that complemented sRisk in patients with low-sRisk (10y-PFS rates 48.1% vs. 87.3%, P=1.2×10-8) and intermediate-sRisk (10y-PFS rates 28.9% vs. 74.1%, P=8.6×10-12). Patients with high cPCs values are associated with higher proliferation and lower apoptosis rates of PC. Circulating-PC > 0.0035% identified MGUS, SMM and MM patients at higher risk of progression or death and predicted a cohort of patients that after relapse from stringent complete response showed shorter OS. These patients could benefit from early consolidation therapy, tandem ASCT or intensive maintenance.

18.
Oncoimmunology ; 10(1): 1986943, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676148

RESUMO

NK and CD8+ T cells are the main cytolytic effectors involved in innate and adaptive tumor immune surveillance, respectively. Although their educational pathways differ, similarities in their development and function suggest that CD8+ T lymphocytes could be sensitive to NK cell licensing signals, which might influence their antitumor response. To demonstrate this hypothesis, we retrospectively evaluated the impact that NK cell licensing interactions have on the expression of CD226 on CD8+ T lymphocytes and on the survival of patients with different hematopoietic and solid cancers (n = 1,023). Prospectively, we analyzed by multiparametric flow cytometry the anti-CD3/CD28-induced proliferation and immune-receptor expression of purified CD8+ T lymphocytes from healthy donors (n = 17) with different combinations of NK cell licensing ligands. Results show that methionine/threonine (M/T) dimorphism at position -21 of the HLA-B leader peptide, but not other HLA class-I dimorphisms involved in the education of NK cells (HLA-C1/C2 or HLA-Bw4), is associated with greater survival and expression of CD226 in cancer patients, which was proportional to the number of methionines present in their genotype. CD8+ T lymphocytes from healthy donors with -21 M showed higher proliferation rates and lower expression of TIGIT after in vitro stimulation. Therefore, CD8+ T lymphocytes, like NK cells, appear to be sensitive to the -21 M/T dimorphism of HLA-B leader peptide, which results in the modulation of CD226 in vivo and the proliferation and expression of TIGIT after in vitro stimulation, all of which could be related to their immune-surveillance capacity and the survival of cancer patients.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Antígenos de Histocompatibilidade Classe I , Humanos , Neoplasias/genética , Estudos Retrospectivos , Antígenos HLA-E
19.
Am J Cancer Res ; 11(9): 4438-4454, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659897

RESUMO

Improved therapies in multiple myeloma (MM) have forced a constant risk stratification update, first Durie-Salmon, then international scoring systems (ISS), next revised-ISS (RISS) including high-risk cytogenetic abnormalities (HRCAs) such as del(17p) and t(4;14), and now R2-ISS including 1q21 gain has been proposed. Predictive value of 1q21 gain by itself or in concurrence with other cytogenetic abnormalities is evaluated in 737 real-world plasma cell neoplasm (PCN) patients under current therapies. Ten-year progression-free survival (10y-PFS) rates for patients with 2, 3 and >3 copies of 1q21 were 72.2%, 42.5% and 43.4% (P<1.1×10-17). Cox regression analysis confirmed that 1q21 gain was an independent prognostic factor for PFS (HR=1.804, P<0.0001, Harrell C-statistic =0.7779±0.01495) but not for OS (P=0.131). Gain of 1q21 was strongly associated with hypodiploidy (38.8% vs. 7.0%, P=1.3×10-22), hyperdiploidy (44.1% vs. 16.4%, P=1.6×10-13), HRCAs (12.6% vs. 3.5%, 1.8×10-5), IGH breaks (12.3% vs. 2.1%, P=2.1×10-7) and del(13q) (8.0% vs. 4.0%, P=0.031). In our series, 1q21 gain by itself did not improve RISS predictive capacity in patients either eligible or ineligible for autologous stem cell transplantation (ASCT). However, compared with patients with other 1q21 gains: concurrence with hyperdiploidy improved the prognosis of ASCT-eligible patients from 62.5% to 96.0% 10-year overall-survival (10y-OS, P<0.002); concurrence with hypodiploidy improved the prognosis of ASCT-ineligible patients from 35.7% to 71.0% (P=0.013); and concurrence with del(13q) worsened the prognosis of ASCT-ineligible patients from 12.5% to 53.4% (P=0.035). Gain of 1q21 should be patient-wisely evaluated, irrespective of the RISS, considering its concurrence with other cytogenetic abnormalities and eligibility for ASCT.

20.
Curr Anesthesiol Rep ; 10(4): 404-415, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33281504

RESUMO

PURPOSE OF REVIEW: The main purpose of this article is to review recent literature regarding multimodal analgesia medications, citing their recommended doses, efficacy, and side effects. The second part of this report will provide a description of drugs in different stages of development which have novel mechanisms with less side effects such as tolerance and addiction. RECENT FINDINGS: Multimodal analgesia is a technique that facilitates perioperative pain management by employing two or more systemic analgesics along with regional anesthesia, when possible. Even though opioids and non-opioid analgesics remain the most common medication used for acute pain management after surgery, they have many undesirable side effects including the potential for misuse. Newer analgesics including peripheral acting opioids, nitric oxide inhibitors, calcitonin gene-related peptide receptor antagonists, interleukin-6 receptor antagonists and gene therapy are under intensive investigation. SUMMARY: A patient's first exposure to opioids is often in the perioperative setting, a vulnerable time when multimodal therapy can play a large role in decreasing opioid exposure. Additionally, the current shift towards faster recovery times, fewer post-operative complications and improved cost-effectiveness during the perioperative period has made multimodal analgesia a central pillar of Enhanced Recovery After Surgery (ERAS) protocols.

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