Impact Of Combination Therapy Research Articles

The impact of combined therapy on healing of foot injuries in runners

Purpose. The structure of the lower body has a very important role as support for the body and is often injured in runners. The aim of this study was to determine whether there is an impact of providing combined therapy on the healing of foot injuries. Material and methods. The type of research used was experimental, with a randomized pretest and posttest group design. The total research sample was 56 runners who were divided into four therapy groups, namely the sports massage, trigger point, chiropractic, and 1 control group. Measurement of the degree of strain uses visual analogue scale (VAS) criteria. Results. From the research results, it is known that providing therapy to the sports massage, trigger point, chiropractic group and 1 control group can reduce the intensity of strain pain (2.35 ± 0.756; 1.63 ± 0.840; 2.24 ± 0.840; 3.71 ± 0.756) with p-value = 0.001. Conclusions. Based on the stages of the research results, it can be concluded: 1) There was a significant impact after being given sports massage, trigger point and chiropractic therapy on reducing pain intensity 15 minutes after treatment; 2) There was no significant difference between the sports massage, trigger point and chiropractic treatment groups on pain intensity 15 minutes after treatment.

Chemotherapy-induced neuropathy and pain in pediatric oncology patients: impact of combination therapies.

Combination therapy stands out as a risk factor for clinical CIPN. The high prevalence of moderate/severe pain underscores the importance of close vigilance given its potential to compromise the patient's overall well-being. • Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse effect and dose-limiting factor in pediatric cancer treatment. • Prevalence varies among regions and risk factors are still under study. • Prevalence of symptomatic CIPN is 23% among pediatric patients undergoing treatment for hematopoietic tumors in a referral hospital in Argentina. Most patients report moderate or severe pain. • Combining vincristine with cytarabine and using a higher number of neurotoxic drugs in combination therapies exhibit significant association with the development of CIPN-related symptoms.

Impact of Combination Therapy with Chemical Drugs and Megavoltage X-ray Exposure on Breast Cancer Stem Cells' Viability and Proliferation of MCF-7 and MDA-MB-231 Cell Lines.

Breast Cancer (BC) is a serious malignancy among women. However, chemotherapy is an important tool for cancer treatments, but the long-term use of chemotherapy drugs may lead to drug resistance and tumor recurrence. Since Breast Cancer Stem Cells (BCSCs) can be the main factor to induce BC treatment resistance and recurrence, investigation of BCSCs signaling pathways can be an effective modality to enhance cancer treatment efficiency. In this study, the effect of metformin, SB203580, and takinib alone or in combination with radiotherapy on MCF-7 and MDA-MB-231 breast cancer cell lines was evaluated. MCF-7 and MDA-MB-231 breast cancer cell lines were treated with metformin, SB203580, and takinib for 24 or 48 hours, followed by X-ray exposure. The MTT assay and flow cytometry analysis were performed to assess cell growth inhibition and cellular death, CXCr4 expression, and BCSCs, respectively. The results showed the combination of takinib/SB203580 with radiotherapy to remarkably reduce the CXCR4 expression and BCSCs levels in the MCF-7 cell line. Also, the concurrent administration of takinib/metformin/radiotherapy significantly reduced BCSCs and CXCR4 metastatic markers in the MDA-MB- 231 cells. Since the MAPK signaling pathway has an important role in inducing drug resistance and cell proliferation, the use of SB203580 as an inhibitor of p38 MAPK can improve breast cancer treatment. Furthermore, metformin and ionizing radiation by suppression of the mTOR signaling pathway can control AMPK activation and cellular proliferation. Anti-cancer and cytotoxic effects of metformin can be effective in this strategy. In conclusion, the combination of conventional chemotherapeutic drugs, including SB203580, metformin, and takinib with X-ray exposure can be a new approach to diminish the drug resistance of breast cancer.

Impact of combination therapy on Ki-67 and Bcl-2 expression in psoriasis

BACKGROUND: Psoriasis is a chronic inflammatory immune-mediated disease characterized by an increased rate of keratinocyte division. Modern ideas about the immunopathogenesis of psoriasis, systemic inflammation and manifestations, comorbid conditions bring to the fore the question of the rational choice of therapy in patients with moderate and severe psoriasis.
 AIM: to study the effect of the combined use of PUVA therapy and methotrexate on the expression levels of receptors for the proliferation marker Ki-67 and the anti-apoptotic protein Bcl-2.
 MATERIALS AND METHODS: The study included 110 patients with moderate to sеvеrе psоriаsis,divided into 2 groups: the first group received PUVA therapy in combination with methotrexate (Mt); the second group received methotrexate (Mt) monotherapy. Skin biopsies were taken from the affected areas in 10 patients from the 1st group before and after therapy for immunohistochemical study to determine the level of expression of Ki-67 and Bcl-2. Healthy skin bioptats were taken from patients operated on for appendicitis and used as the control samples.
 RESULTS: An immunohistochemical study revealed a statistically significant increase in the initial indicators of the expression level of Ki-67 and Bcl-2 in all patients with psoriasis compared with the control group. As a result of the combined therapy, there was a significant decrease in the expression of Ki-67 and Bcl-2.
 CONCLUSION: The combined method of treatment of patients with psoriasis has an immunosuppressive effect, as evidenced by a significant decrease in the expression of the proliferation marker Ki-67 and the apoptosis inhibitor Bcl-2.

Approach to the patient with suspected hypereosinophilic syndrome.

Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders with clinical manifestations ranging from fatigue to life-threatening endomyocardial fibrosis and thromboembolic events. Given the broad differential diagnosis of HES, a comprehensive approach is needed to identify potential secondary (treatable) causes and define end-organ manifestations. Classification by clinical HES subtype is also useful in terms of assessing prognosis and guiding therapy. Corticosteroids remain the mainstay of initial therapy in the setting of acute, life-threatening PDGFR mutation-negative HES. Whereas the recent availability of eosinophil-targeted therapies with extraordinary efficacy and little apparent toxicity is changing the treatment paradigm, especially for idiopathic HES and overlap syndromes, questions remain unanswered regarding the choice of agent, impact of combination therapies, and long-term effects of eosinophil depletion. This review provides a case-based discussion of the differential diagnosis of HES, including the classification by clinical HES subtype. Treatment options are reviewed, including novel eosinophil-targeted agents recently approved for the treatment of HES and/or other eosinophil-associated disorders. Primary (myeloid) disorders associated with hypereosinophilia are not be addressed in depth in this review.

The Impact of Combination Therapy with Rivaroxaban and Acetylsalicylic Acid in Patients with Coronary Heart Disease on the Achievement of the Target for Reducing Mortality from Cardiovascular Diseases of the Federal Project "Fight against Cardiovascular Diseases"

Aim. To assess the outcomes of combination therapy with rivaroxaban and acetylsalicylic acid (ASA) in patients with stable coronary artery disease (CAD) and a high risk of thrombotic events on the set targets of Ministry of Health for reduction of cardiovascular mortality in Russia.Material and methods. The development of the model for analysis in MS Excel included the following stages: calculation of the population of patients with stable CAD who can be treated with combination therapy (rivaroxaban and ASA); calculation of the number of deaths due to cardiovascular disease (CVD), number of strokes and myocardial infarction (MI) in the current scenario (patients receive monotherapy with ASA) and simulated scenario (some patients switch from monotherapy to combination therapy); estimation the impact of the number of avoided cases of deaths due to combination therapy on set target for reducing CVD mortality in 2024 year; sensitivity analysis to assess the sustainability of outcomes.Results. Total number of eligible patients for combination therapy was estimated as 1.08 million patients. Based on the simulation results, it was determined that with the reallocation of patients from monotherapy with ASA to combination therapy with rivaroxaban and ASA, the number of avoided deaths in 2022 will be 973 cases, in 2023 – 1,622 cases, in 2024 – 3,245 cases, which will make it possible to reach 6.7%, 7.4% and 11.1% of the set target for reduction of mortality from CVD in the respective years. In addition, the gradual reallocation of patients from monotherapy to combination therapy might decrease the cases of stroke and MI in 973 and 649 cases by 2022, 1,622 and 1,082 cases by 2023, and 3 245 and 2 163 cases by 2024 year, respectively. Sensitivity analysis showed that outcomes are sustainable.Conclusion. The use of combination therapy of rivaroxaban and ASA in patients with stable CAD and high thrombotic risk will allow to achieve up to 11.1% of the set target for reduction of mortality from CVD by 2024 in Russia and can also potentially impact on another set target for reduction mortality from cerebrovascular diseases by reducing the number of strokes. Thereby, this therapy can be considered for drug provision programmes for patients with stable CAD and high thrombotic risk to fulfill the goals to reduce mortality from CVD.

The impact of combination therapy with Femoklim and Nervo-Vit on the psychological state of women with estrogen deficiency and metabolically healthy obesity

The impact of combination therapy with Femoklim and Nervo-Vit on the psychological state of women with estrogen deficiency and metabolically healthy obesity

630. Emergence of Colistin Resistance in the OVERCOME Trial: Impact of Combination Therapy with Meropenem

BackgroundColistin (COL) remains an important therapeutic option for carbapenem-resistant (CR) Gram-negative bacilli (GNB). COL is often utilized in combination with meropenem (MEM), in part due to concerns regarding the development of COL resistance with monotherapy. We recently completed a randomized controlled trial comparing outcomes in patients receiving COL + placebo to those receiving COL + MEM; herein we present data on the emergence of COL resistance in this trial.MethodsOVERCOME was an international, multicenter, randomized, double-blind, placebo-controlled study comparing COL and COL + MEM for the treatment of bloodstream infection and/or pneumonia due to CR GNB. Subjects were included in the modified intent to treat population (mITT) if their enrollment pathogen had a COL MIC ≤2 mg/L, as determined by broth microdilution (BMD). Daily blood and/or respiratory samples were obtained in patients per protocol until two consecutive negatives were obtained or the end of study treatment. All subsequent isolates were evaluated for COL resistance via BMD, defined as MIC ≥ 4 mg/L. ResultsOf the 425 patients in the mITT population, 380 (191 COL; 189 COL + MEM) were evaluable for the endpoint of COL resistance development. The median age of the cohort was 70, 38% were female, 47% were white, and 45% were Asian. 70% had an index infection of pneumonia, 68% were in the intensive care unit at the onset of their infection, and A. baumannii was the most common pathogen (78% of patients). Baseline characteristics, infection type, severity of illness, and index pathogen were similar amongst treatment arms. No significant difference in resistance development was seen between the COL and COL + MEM groups overall (12% vs. 8%; p = 0.31), or in any subgroup (Table). In patients with A. baumannii, there was a trend towards decreased resistance development with COL + MEM (13.3% vs 7.5%; p = 0.13).ConclusionWe were unable to identify a significant difference in resistance emergence between treatment arms, but given the low incidence of this outcome, were underpowered to do so. The impact of COL + MEM on preventing emergence of COL resistance in A. baumannii warrants further clinical study. Disclosures Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support) Emmanuel Roilides, MD, PhD, FIDSA, FAAM, FESCMID, Merck Sharp & Dohme Corp. (Consultant, Grant/Research Support) Matthew Sims, MD, PhD, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor)

The impact of combination therapy with metformin and exogenous vitamin D on hypothalamic-pituitary-thyroid axis activity in women with autoimmune thyroiditis and high-normal thyrotropin levels.

Metformin was found to decrease thyrotropin levels in subjects with non-autoimmune but not with autoimmune hypothyroidism. Vitamin D reduced thyroid autoimmunity without affecting thyrotropin and thyroid hormone levels. The aim of the current study was to investigate whether exogenous vitamin D modulates the impact of metformin on hypothalamic-pituitary-thyroid axis activity in young women with autoimmune thyroiditis. This case-control study included 32 prediabetic women with Hashimoto's thyroiditis, high-normal thyrotropin levels (2.5-4.5mIU/L) and vitamin D insufficiency. Based on patient preference, these individuals received either metformin (3g daily) plus vitamin D (4000IU daily) (n=17) or were treated with only metformin (3g daily) (n=15). Plasma levels of glucose, serum levels of insulin, thyrotropin, total and free thyroid hormones and 25-hydroxyvitamin D, as well as serum titres of thyroid antibodies, were assessed at baseline and 6months later. Thirty-one women completed the study. At baseline, there were no differences between the treatment groups. In both study arms, metformin reduced plasma glucose levels and improved insulin sensitivity but this effect was stronger in subjects receiving vitamin D. Only metformin administered with vitamin D decreased thyrotropin levels, increased 25-hydroxyvitamin D levels and reduced thyroid antibody titres. The impact on thyrotropin and antibody titres correlated with the increase in 25-hydroxyvitamin D levels and with the improvement in insulin sensitivity. This study has shown for the first time that exogenous vitamin D potentiates the impact of metformin on thyrotropin levels in women with autoimmune thyroiditis.

Evaluation of Addition of Intravenous Metronidazole to Oral Vancomycin Therapy in Critically Ill Patients with Non-Fulminant Severe Clostridioides difficile Infection.

Data on the impact of combination therapy (intravenous metronidazole [IV MTZ] plus oral vancomycin [PO VAN]) on clinical outcomes in intensive care unit (ICU) patients with severe non-fulminant Clostridioides difficile infection (CDI), including NAP1-positive samples, are lacking. Retrospective observational cohort of adult patients who developed CDI in the ICU diagnosed with severe non-fulminant CDI who received PO VAN. Patients with an order for IV MTZ started within 72hours of PO VAN and who received at least 72hours of combined therapy composed the combination therapy group. A subset of patients had stool samples collected for NAP1 testing. An additional subset was matched by Acute Physiology and Chronic Health Evaluation (APACHE) II scores. The primary outcome was inpatient all-cause mortality within 30 days of CDI diagnosis. A total of 138 patients were included with 60 (43.5%) patients in the combination group. Compared with the PO VAN group, those in the combination group had higher white blood cell counts at diagnosis (15.9 [interquartile range (IQR) 10.2-21.1] vs 20.9 [IQR 16.2-29] cells/mm3 , p<0.001), respectively. Overall inpatient mortality was higher in the combination group, but 30-day mortality was not significantly different between groups (12.8% monotherapy vs 18.3% combination, p=0.371). This finding was the same for the 96 patients in the APACHE II-matched subgroup, 14.6% monotherapy versus 18.8% combination, p=0.785. NAP1 testing was completed in 42 patients; 11 were positive (26.2%). Patients who were NAP1 positive were more likely to receive IV MTZ (54.5% vs 19.4%, p=0.026). Compared with PO VAN, combination therapy with IV MTZ was not associated with better clinical outcomes in severe non-fulminant CDI in ICU patients.

Reduction in anxiety during treatment with exercise and duloxetine is related to improvement of low back pain-related disability in patients with non-specific chronic low back pain.

Background: Non-invasive treatment is generally recommended for patients with non-specific chronic low back pain (CLBP). However, the impact of combination therapy with physical exercise and a serotonin-norepinephrine reuptake inhibitor has not been clarified in patients with non-specific CLBP. This study assessed the efficacy of combination treatment with exercise and duloxetine on non-specific CLBP and aimed to identify factors that contributed to improvement of LBP-induced disability.Methods: This prospective study was conducted on consecutive outpatients with non-specific CLBP. Patients received a supervised home-based exercise program and duloxetine administration for 15 weeks. The Roland-Morris Disability Questionnaire (RDQ), Numerical Rating Scale (NRS), Hospital Anxiety and Depression Scale (HADS), and Pain Catastrophizing Scale (PCS) were assessed at baseline and 15 weeks. Multiple logistic regression modeling was used to identify factors associated with an improvement in RDQ. Results: Forty-two patients were enrolled. Overall, scores on the RDQ, NRS, and PCS (total score, magnification, helplessness) were significantly reduced at 15 weeks (p < 0.01 for all). An improvement of disability was confirmed in 22 patients (52%). A higher HADS depression score before and after the intervention was significantly associated with a lack of improvement in disability (p < 0.01). Further, a reduction in HADS anxiety score over 15 weeks was a significant factor associated with an improvement in disability (odds ratio: 1.99;95% CI: 1.26-3.65). Conclusions: Supervised exercise plus duloxetine resulted in favorable outcomes and an improvement of LBP-related disability in approximately 50% of patients. A reduction in anxiety over treatment was associated with the improved disability.

A mathematical study of the impact of cell plasticity on tumour control probability.

The tumour control probability (TCP) is a treatment planning tool that evaluates the probability of tumour eradication and helps in the assessment of the relative efficacy of different radiotherapy regimens. The response of tumours to radiation differs greatly even between patients with same types of cancers. Tumour heterogeneity or cellular diversity among cancer cells has a pronounced impact on the success of administered radiotherapy protocols. Tumour heterogeneity can be explained using the cancer stem cells (CSCs) hypothesis, which posits that CSCs are responsible for tumour initiation and propagation as well as therapeutic resistance. Moreover, the existence of plasticity or bidirectional transition between CSCs and non-CSCs indicates that, sometimes, non-CSCs appear to mimic CSC phenotypes, resulting in an increase in resistance. Here, we have developed a stochastic model to investigate the impact of plasticity on the efficacy of radiotherapy. The effect of plasticity on TCP is explored by applying the model to standard and hyper-fractionated schedules for a three week period of treatment as well as standard, hyper-fractionated, and accelerated hyper-fractionated schedules with an equal total dose of 30 Gy. Our results confirm that tumour control becomes increasingly difficult in the presence of plasticity as well as for the most resistant tumours. For the case with equal total dose, it is observed that increasing fractionation, at first enhances the probability of CSCs and tumour removal, but ultimately results in lower TCPS+P and TCPS. In addition, the combination of radiotherapy and targeted therapy (with increasing CSC differentiation) improves both the probability of CSC and tumour removal, in the absence of plasticity. However, in the presence of plasticity, the impact of combination therapy is not significant.

Immune Checkpoint Inhibition in Non-metastatic Non-small Cell Lung Cancer: Chance for Cure?

Immune checkpoint inhibition of programmed-death receptor 1 (PD-1) or its ligand (PD-L1) has become a standard in the treatment of metastatic non-small cell lung cancer, either as monotherapy or in combination. Recently, it could be shown that immunotherapy works as consolidation after chemoradiotherapy in locally advanced disease if the tumours express PD-L1. A significant and meaningful survival benefit for consolidation with durvalumab after chemoradiotherapy compared to chemoradiotherapy alone was observed in the PACIFIC trial. In addition, there is a growing body of evidence that this treatment modality is also effective in a neoadjuvant setting in early stages, whereas the role as adjuvant treatment after surgery needs to be determined. The impact of combination therapies in non-metastatic stages-either neoadjuvant or adjuvant-needs to be evaluated in future trials. It is yet unclear whether PD-L1 and tumour mutational burden are predictive biomarkers as randomised trials are missing.

Impact of combination therapy with anti-PD-1 blockade and a STAT3 inhibitor on the tumor-infiltrating lymphocyte status

Recently, clinical studies using anti-immune checkpoint molecule antibodies have been successful in solid tumors, such as melanoma and non-small cell lung cancers. However, pancreatic cancers are still intractable and difficult to treat once recurrence or metastasis occurs; thus, novel combined use of immune checkpoint blockade (ICB) with molecular targeted drugs is considered a therapeutic option.Previously, we developed a novel humanized MHC-double knockout (dKO) NOG mouse model and demonstrated that an anti-PD-1 antibody or a STAT3 inhibitor showed anti-tumor effects through an immunological mechanism.In the current study, using a humanized mouse model, we aimed to develop a combination therapy with an anti-PD-1 antibody and a STAT3 inhibitor (STX-0119) for use in vivo against pancreatic cancer. In an in vitro investigation, STX-0119 showed weak to moderate cytotoxic activity against several pancreatic cancer cell lines, which exhibited activated pSTAT3 and weak PD-L1 expression.However, unexpectedly, an in vivo study indicated that the combination of the anti-PD-1 antibody with STX-0119 remarkably reduced the anti-tumor effect and TIL numbers despite the effective anti-tumor activity against pancreatic cancer was produced individually by STX-0119 and the anti-PD-1 antibody.These results suggested that the combination of an anti-PD-1 antibody with specific signal inhibiting drugs should be carefully evaluated to avoid unexpected side effects, and such studies might contribute to the development of an effective combination regimen of ICB with cancer-targeting drugs such as tyrosine kinase inhibitors (TKIs).

Chrysin in Combination with Insulin Promotes Glucose Uptake in Skeletal Muscle Cell: Impact of Combination Therapy in Diabetes Myopathy (P01-031-19)

ObjectivesThe objective of the current study was examining the beneficial effects of DPP4 inhibitor chrysin alone and in combination with insulin benefits diabetes myopathy. MethodsSulforhodamine B (SRB) protein-dye was used to determine the acute toxicity, and 1H NMR spectroscopy was used to identify and quantify glucose levels to assess glucose uptake on treatments chrysin and combination of chrysin with Insulin on differentiated skeletal muscle cells. Pathway analysis was carried out using omics net web server. All experiments were conducted in triplicates, and all data in the graph represent Mean ± S.D. Graph pad software was used to calculate One-way analysis of variance (ANOVA), computed p-value among different groups and values with P < 0.05 is significant. ResultsResults showed that 250 μM chrysin and combination (10 nM Insulin with 250 μM chrysin) treatments are not acutely toxic to skeletal muscle cells and proliferates the cells significant to insulin-treated skeletal muscle cells (Figure 1A). Glucose metabolite levels are studied as skeletal muscle cells adopted cell proliferative and to demonstrate our hypothesis on glucose metabolism. Significant differences were observed in skeletal muscle cells treated with insulin, chrysin, and combination (Figure 1B). It is observed that chrysin alone, combination increases glucose uptake significantly in comparison to control cells. Pathway analysis revealed that GPCR signaling and immune-related signaling plays a role in proliferating skeletal muscle cells to regulate glucose metabolism. ConclusionsThe results of this study propose the use of natural compound chrysin in combination with insulin to promote skeletal muscle health in diabetes mellitus. The combination identified herein must be considered for future therapies to control diabetic myopathy in preclinical and clinical studies. Chrysin can also be applied as a supplement in the diet as well, to control diabetic myopathy. Funding SourcesAuthors wish to express their gratitude to Escuela Nacional de Ciencias Biológicas-Instituto Politécnico Nacional (ENCB-IPN) for providing financial support for the present study. Supporting Tables, Images and/or Graphs▪

Clinical Outcomes at 2 Years Between Beta-Blockade with ACE Inhibitors or ARBs in Patients with AMI Who Underwent Successful PCI with DES: A Retrospective Analysis of 23,978 Patients in the Korea AMI Registry.

Data concerning the clinical impact of combination therapy with β-blockers (BBs) + angiotensin-converting enzyme inhibitors (ACEIs) compared with BBs + angiotensin-receptor blockers (ARBs) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) are limited. We compared the clinical outcomes at 2years between these two combination therapies. We enrolled 23,978 patients with AMI who underwent successful PCI with DES between January 2005 and June 2015 from the Korea AMI Registry (KAMIR) and divided them into the two groups: BB + ACEI (n = 17,310) and BB + ARB (n = 6668). The primary endpoint was major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (re-MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and non-TVR. The secondary endpoints were the cumulative incidences of individual components of MACE and target vessel failure (TVF), a composite of death related to the target vessel, re-MI, or clinically driven TVR. The relative risk of MACE was higher in the BB + ARB group than in the BB + ACEI group after propensity score-matched (PSM) analysis (hazard ratio [HR] 1.204; 95% confidence interval [CI] 1.057-1.370; p = 0.005). The relative risks of all-cause death (HR 1.435 [95% CI 1.117-1.845]; p = 0.005), cardiac death (HR 1.733 [95% CI 1.253-2.396]; p = 0.001), TVR (HR 1.437 [95% CI 1.157-1.784]; p = 0.001), and TVF (HR 1.231 [95% CI 1.065-1.424]; p = 0.005) were also higher in the BB + ARB group after PSM. The BB + ACEI group demonstrated reduced cumulative incidences of MACE, all-cause death, cardiac death, TVR, and TVF compared with the BB + ARB group in patients with AMI who underwent successful PCI with DES during a 2-year follow-up period.

Approaches to treat immune hot, altered and cold tumours with combination immunotherapies.

Immunotherapies are the most rapidly growing drug class and have a major impact in oncology and on human health. It is increasingly clear that the effectiveness of immunomodulatory strategies depends on the presence of a baseline immune response and on unleashing of pre-existing immunity. Therefore, a general consensus emerged on the central part played by effector T cells in the antitumour responses. Recent technological, analytical and mechanistic advances in immunology have enabled the identification of patients who are more likely to respond to immunotherapy. In this Review, we focus on defining hot, altered and cold tumours, the complexity of the tumour microenvironment, the Immunoscore and immune contexture of tumours, and we describe approaches to treat such tumours with combination immunotherapies, including checkpoint inhibitors. In the upcoming era of combination immunotherapy, it is becoming critical to understand the mechanisms responsible for hot, altered or cold immune tumours in order to boost a weak antitumour immunity. The impact of combination therapy on the immune response to convert an immune cold into a hot tumour will be discussed.

Impact of Combination Therapy with Ezetimibe/Simvastatin Treatment on the Neointimal Response to Biodegradable Polymer Biolimus-Eluting Stent Implantation in Patients with Acute Myocardial Infarction: Serial Assessment with Optical Coherence Tomography

The aim of this study was to compare the neointimal response at 12-month follow-up between ezetimibe/simvastatin (Vytorin, manufactured by Merck) 10/10 mg and Vytorin 10/40 mg after biodegradable polymer Biolimus-eluting stent (BP-BES) implantation in patients with acute myocardial infarction (AMI). A total of 20 patients requiring revascularization were randomly assigned to receive either Vytorin 10/10 mg (n = 9) or Vytorin 10/40 mg (n = 11). Baseline optical coherence tomography (OCT) was performed after stent implantation, and follow-up OCT was scheduled at 12 months. We performed follow-up OCT in 18 patients (Vytorin 10/10 mg (n = 9) or Vytorin 10/40 mg (n = 9)). A total of 842 frames and 8552 struts were analyzed at initial and follow-up OCT. At follow-up, the percentage of uncovered struts was not significantly different between both groups (6.61 ± 10.29% vs. 7.57 ± 6.45%, p = 0.815). The percentage of malapposed struts was also similar between both groups (0.69 ± 1.58% vs. 1.55 ± 2.72%, respectively, p = 0.422). Mean percent neointimal hyperplasia area was not significantly different between both groups (6.53 ± 3.26% vs. 6.37 ± 8.96%, p = 0.961). This OCT study showed that both high- and moderate-intensity dosing of Vytorin was associated with relatively lower percentages of uncovered struts and malapposed struts after Biolimus A9-eluting stent implantation in patients with AMI.

The Impact of Combination Therapy on Infliximab Levels and Antibodies in Children and Young Adults With Inflammatory Bowel Disease.

The aim of this study was to evaluate the effect of combination therapy with methotrexate or 6-mercaptopurine on infliximab levels (IFXL) and antibodies to infliximab (ATI). Infliximab (IFX) is a highly effective therapy for inflammatory bowel disease (IBD). Unfortunately, 25%-50% of patients will lose response to IFX. Loss of response is correlated with low IFXL and ATI formation which accelerates drug clearance. Combination therapy is thought to decrease ATI formation. We performed a cross-sectional analysis of 223 pediatric and young adult patients with IBD on IFX. IFXL and ATI were measured and compared between subjects on current combination therapy, prior combination therapy, and IFX monotherapy. Eighty-four (37.7%) patients were on combination therapy and 139 (62.3%) were on IFX monotherapy. Within the current monotherapy group, 112 (80.6%) had previously been on combination therapy, while 27 (19.4%) had never been on a concomitant immunomodulator. Patients currently on combination therapy had a higher IFXL (17.00 ± 1.33 μg/mL) than those currently on IFX monotherapy (13.18 ± 1.26 μg/mL), P < 0.01. IFXL was lowest in patients who had never been on combination therapy (11.53 ± 2.05 μg/mL) and highest in patients currently on combination therapy (17.00 ± 1.33 μg/mL). Patients currently on combination therapy had a lower rate of detectable ATI (9.5%) compared with those on monotherapy (20.0%) in multivariate analysis (odds ratio [OR]: 0.3; 95% confidence interval (CI), 0.1-0.7, P < 0.01). Current or prior combination therapy is associated with higher IFXL and lower rates of ATI formation.

Arnica and Bromelain for Blepharoplasty-Associated Ecchymosis

Homeopathic and naturopathic supplementation has gained increasing popularity as complementary and alternative medicine (CAM) modalities. Arnica and Bromelain are 2 commonly used supplements thought to be effective in reducing ecchymosis. This study was designed to explore the impact of combination therapy with Arnica and Bromelain on postoperative ecchymosis in patients undergoing blepharoplasty. In total, 130 patients undergoing upper eyelid blepharoplasty were enrolled. Patients with bleeding diatheses or inability to comply with cessation of anticoagulants were excluded. Aspirin and all naturopathic and homeopathic treatments were discontinued 2 weeks prior to surgery. In all, 64 patients received oral Arnica and Bromelain treatment starting 7 days prior to surgery and extending 7 days postoperatively. Sixty-six patients received no supplementation. Upper eyelid blepharoplasty was performed with skin flap excision, hemostasis with electrocautery, and closure with running 6-0 fast absorbing plain gut. Postoperative photos were taken 7 days following surgery. Photos were analyzed by 2 blinded reviewers, who graded the severity of ecchymosis using a visual analog scale. All 130 patients were seen during the postoperative course. There were no patients lost to follow-up, and there were no adverse reactions to the treatment protocol that necessitated discontinuation of Arnica and Bromelain. Average ecchymosis in the treatment arm was 5.00 compared with 4.43 in the control arm ( P = .67). At the conclusion of this study, the investigators find insufficient evidence that the combination of Arnica and Bromelain is effective at producing a statistically significant difference in ecchymosis following upper eyelid blepharoplasty.