Personalized Versus Non-personalized Nutritional Recommendations/Interventions for Type 2 Diabetes Mellitus Remission: A Narrative Review.

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.

Perioperative Pain Management and Cancer Outcomes: A Narrative Review.

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.

Incidence of acute kidney injury after noncardiac surgery in patients receiving intraoperative dexmedetomidine: a retrospective study.

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.

Total intravenous anesthesia versus inhalation anesthesia: how do outcomes compare?

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.

Opioid use, misuse, and abuse: a narrative review about interventions to reduce opioid consumption and related adverse events in the perioperative setting.

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.

Perioperative pain, analgesics and cancer-related outcomes: where do we stand?

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.

Temperature management during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

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.

Anesthesia Techniques and Long-Term Oncological Outcomes.

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.

Predictive value of 1q21 gain in multiple myeloma is strongly dependent on concurrent cytogenetic abnormalities and first-line treatment.

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.

CD8+ T lymphocytes are sensitive to NKG2A/HLA-E licensing interaction: role in the survival of cancer patients.

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.

Low-affinity immunoglobulin gamma Fc region receptor III-B (FcγRIIIB, CD16B) deficiency in patients with blood and immune system disorders.

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.

Blood-based risk stratification for pre-malignant and symptomatic plasma cell neoplasms to improve patient management.

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.

Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms.

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.

Opioids and cancer prognosis: A summary of the clinical evidence.

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.

Optimizing Perioperative Use of Opioids: A Multimodal Approach.

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.

KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling.

Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved.

Anesthesia Options and the Recurrence of Cancer: What We Know so Far?

Surgery is a critical period in the survival of patients with cancer. While resective surgery of primary tumors has shown to prolong the life of these patients, it can also promote mechanisms associated with metastatic progression. During surgery, patients require general and sometimes local anesthetics that also modulate mechanisms that can favor or reduce metastasis. In this narrative review, we summarized the evidence about the impact of local, regional and general anesthesia on metastatic mechanisms and the survival of patients. The available evidence suggests that cancer recurrence is not significantly impacted by neither regional anesthesia nor volatile or total intravenous anesthesia.

Low-cost media statistical design for laccase rPOXA 1B production in P. pastoris.

Laccases (E.C. 1.10.3.2) are multicopper oxidases of great importance in the industry due to their non-specificity and high oxidative potential. Laccases are useful to bleach synthetic dyes, oxidize phenolic compounds and degrade pesticides, among others. Hence, the objective of this work was to optimize low cost culture media for recombinant (rPOXA 1B) laccase production from Pleurotus ostreatus in Pichia pastoris. To this end, low cost nitrogen sources were studied, such as malt extract, isolated soy protein and milk serum. Following, two central composite designs (CCD) were performed. In CCD-1 different concentrations of glucose USP (0-13.35 gL-1), protein isolated soy protein (5-25 gL-1), malt extract (3.5-17.5 gL-1) and (NH4)2SO4 (1.3-6.5 gL-1) were evaluated. In CCD-2 only different concentrations of glucose USP (7.9-22 gL-1) and isolated soy protein (15.9-44.9 gL-1) were evaluated. CCD-2 results led to a One Factor Experimental design (OFED) to evaluate higher isolated soy protein (20-80 gL-1) concentrations. In all designs, (CCD-1, CCD-2 and OFED) CuSO4 (0.16 gL-1) and chloramphenicol (0.1 gL-1) concentrations remained unchanged. For the OFED after sequential statistical optimization, an enzyme activity of 12,877.3 ± 481.2 UL-1 at 168 h was observed. rPOXA 1B activity increased 30.54 % in comparison with CCD-2 results. Final composition of optimized media was: 20 gL-1 glucose USP, 50 gL-1 isolated soy protein 90 % (w/w), 11.74 gL-1 malt extract, and 4.91 gL-1 (NH4)2SO4. With this culture media, it was possible to reduce culture media costs by 89.84 % in comparison with improved culture media previously described by our group.