Tumor-infiltrating T-Lymphocyte immunity-related immune tolerance and anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy for advanced hepatocellular carcinoma

Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.

Progress of Immunotherapy Combined with Anti-Angiogenesis Therapy in Lung Cancer

Lung cancer is the most prevalent and fatal cancer in China and even around the world, and many patients are found in the late stage of lung cancer. For the treatment of advanced lung cancer, in addition to traditional chemotherapy modalities, many emerging treatments are increasingly significant, such as immunotherapy, anti-angiogenic therapy, and targeted therapy. An increasing number of studies have now shown that anti-angiogenic therapy improves the immune microenvironment by enhancing tumor immunity through normalization of tumor vessels. Immunization combined with anti-angiogenic therapy can exert synergistic effects and improve the prognosis of patients. This article summarizes the extent of benefit, current clinical study data, and future prospects of immunotherapy combined with anti-angiogenic agents in the treatment of advanced NSCLC.

Menstrual Abnormalities and Gynaecological Problems in Women on Anticoagulant and Antiplatelet Therapy: Management Options

Introduction: The aim of this study was: 1) To study the pattern of menstrual abnormality and severity in women on anticoagulant and antiplatelet drugs. 2) To analyze the correlation of prothrombin time (PT), International Normalised ratio (INR) and the bleeding severity. 3) To discuss the various management options in unexpected emergencies and menstrual complications in this subset of women on anticoagulants. Material & Methods: It is a prospective study, over a period of 18 months from July 2011 to december 2012. We had 44 women on antithrombotic therapy. 32 women were on anticoagulants and 12 were on antiplatelet agents. The severity of bleeding pattern was assessed with pictoral bleeding assessment chart (PBAC). 1) Out of 44 women studied, 32 women were on anticoagulants and 12 were on antiplatelet agents. 26 (81.25%) were on acenocoumarol, 5 (15.62%) on warfarin, 1 (3.12%) on heparin, among the 12 antiplatelet users, 8 (66.66%) were on aspirin and 4 (33.33%) on clopidogrel. 2) The indication for anticoagulants was mitral valve replacement (MVR) in 9, double valve replacement (DVR) in 6, aortic valve replacement (AVR) in 3, severe pulmonary artery hypertension (PAH) in 2, severe mitral stenosis (MS) with atrial thrombus in 2, deep vein thrombosis (DVT) in 5, severe mitral regurgitation (MR) in one, the other indications were subdural hematoma, thromboendarterectomy, chronic kidney disease (CKD) stage V, coarction of aorta, one each. The indication for antiplatelet therapy was percutaneous transluminal coronary angioplasty (PTCA) in 3, Wolf Parkinson White (WPW) syndrome + atrial fibrillation (AF), acute myocardial infarction (AMI), coronary artery bypass graft (CABG), mid basilar artery aneurysm, renal allograft recipient, dialated cardiomyopathy, aortic aneurysm repair, hypertension and unstable angina one each. Results: In women on anticoagulants (32), the main complaint was menorrhagia/heavy menstrual bleeding (HMB) in 20, polymenorrhoea with menorrhagia in 4, continuous per vaginal (PV) bleeding in 6. One lady had postmenopausal bleeding. Among the 12 antiplatelet users the main complaint was menorrhagia in 8, polymenorrhoea with menorrhagia in 2, postmenopausal bleeding in one. While on antithrombotic therapy apart from heavy menstrual bleeding, two women had intraperitoneal bleeding, two had post menopausal bleeding, two had secondary postpartum bleeding (PPH). CVA due to embolic stroke occurred in three, one during the study period. Subchoroidal haemorrhage causing choroidal detachment was noted in one. Conclusions: In patients with prolonged INR, excessive uterine bleeding can be an alerting initial manifestation. Antithrombotic therapy can cause HMB or exaggerate the symptom of HMB due to an underlying gynaec pathology. Mefanamic acid and norethisterone were used to arrest heavy menstrual bleeding. Antithrombotic therapy in women needs special consideration with alterations in menstrual pattern and contraception. Pregnancy and postpartum period present special challenges.

Exploration and Study of Jianpi Qushi Powder Combined with Standard Anti HP Quadruple Therapy in the Treatment of HP Infectious Gastritis of Spleen Deficiency and Dampness Stagnation Type

Objective: To explore the therapeutic effect of traditional Chinese medicine Jianpi Qushi powder combined with standard anti-HP quadruple therapy in the treatment of HP infectious gastritis with spleen deficiency and dampness stagnation. Methods: From January 2020 to December 2021, 223 patients with laboratory-confirmed HP infection who were admitted to the Outpatient and Inpatient Department of Internal Medicine in our hospital were selected as the research objects and randomly divided into two groups. 101 patients in the control group were given standard anti HP quadruple therapy;122 cases in the treatment group were given traditional Chinese medicine Jianpi Qushi powder combined with standard anti HP quadruple therapy. The two groups were rechecked carbon breath test after the designed course of treatment, and the curative effects of the two groups were compared. Results: 113 cases in the treatment group were cured by traditional Chinese medicine Jianpi Qushi powder combined with standard anti HP quadruple therapy, and the cure rate was 92.62%. 84 cases in the control group were cured by standard anti HP quadruple therapy, and the cure rate was 83.17%, χ2 = 4.7955, P = 0.0285, the difference was statistically significant (P < 0.05). Conclusion: Traditional Chinese medicine Jianpi Qushi powder combined with standard anti HP quadruple therapy in the treatment of HP infectious gastritis with spleen deficiency and dampness stagnation is one of the best treatment schemes for HP infection. The results of this study achieve the best clinical treatment effect, and provide a more valuable and reliable method for the treatment of gastropathy in clinical internal medicine, which is worthy of popularization and application.

Hepatitis C: From inflammatory pathogenesis to antiinflammatory/hepatoprotective therapy

Hepatitis C virus(HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals(DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with antiinflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanismsof HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection.

Pancreatic tuberculosis mimicking pancreatic carcinoma during anti-tuberculosis therapy:A case report

Pancreatic tuberculosis(TB) is a rare condition,even in immunocompetent hosts.A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient.The patient was admitted to our hospital after suffering for nine days from epigastralgia and obstructive jaundice.Computed tomography revealed a pancreatic mass that mimicked a pancreatic head carcinoma.The patient had undergone an operation four months prior for thoracic TB and was undergoing anti-TB therapy.A previous abdominal ultrasound was unremarkable with the exception of gallbladder steroid deposits.The patient underwent surgery due to the progressive discomfort of the upper abdomen and a mass that resembled a pancreatic malignancy.A biopsy of the pancreas and lymph nodes was performed,revealing TB infection.The patient received a cholecystostomy tube and recovered after being administered standard anti-TB therapy for 15 mo.This case is reported to emphasize the rarecontribution of pancreatic TB to pancreatic masses and obstructive jaundice.

Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy

AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers (mCRCs) addicted to epidermal growth factor receptor (EGFR) signalling.METHODS: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting mCRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of PubMed, Medline and Web of Science to identify eligible papers until March 21st, 2016 using these following terms: ‘‘colorectal cancer’’, “predictive biomarkers’’, “anti-EGFR therapy”, “KRAS”, “NRAS’’, “PIK3CA”, “TP53”, “PTEN”, ‘‘EGFR”, “MET”, “HER2”, “epiregulin”, “amphiregulin”, “prognostic biomarkers”, “BRAF”, “miRNA” and “antibody-dependent cell-mediated cytotoxicity (ADCC) activity”. Two investigators independently evaluated and extracted data from each identified studies based on selected criteria of inclusion and exclusion.RESULTS: The introduction of agents targeting EGFR such as cetuximab and panitumumab increased overall survival of mCRCs. Nevertheless, it has firstly became evident that response rates to cetuximab regimens in unselected patient populations were typically lower than 30%. Clinical data confirmed the predictive value of RAS mutations for resistance to cetuximab and panitumumab leading to the license of these monoclonal antibodies exclusively for the management of patients with RAS-wild type colorectal cancers. So far the identification of predictive biomarkers have generated interesting, though preliminary and, at times, conflicting data on the importance of tumour mRNA levels of EGFR ligands, of activating mutations in other genes such as NRAS and PIK3CA. The prognostic value of selected microRNAs level and ADCC activity is under investigation, while the prognostic impact of BRAF status remains controversial.CONCLUSION: This review focuses on the personalized treatment of mCRC and discusses the potential of new prognostic and predictive biomarkers in selecting patients treated with anti-EGFR therapy.

Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

AIM:To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients. METHODS:Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and "high-grade" tumor budding was defi ned as 15 buds/high-power f ield.RESULTS: Tumor buds and K-RAS mutation both correctly classif ied 68% of patients. All patients with K-RAS mutation (n=7) or high-grade tumor budding (n=11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% CI): 2.8 (1.3-6.0, P=0.008)].CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting.

An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy

AIM： To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema（DME） resistant to anti-vascular endothelial growth factor（VEGF） therapy.METHODS： Thirty-two DME patients were enrolled.A700 microgram slow release Intravitreal Dexamethasone Implant（Ozurdex~） was placed in the vitreous cavity.All patients were followed for 18 mo.Best-corrected visual acuity（BCVA） measured with Early Treatment Diabetic Retinopathy Study（ETDRS） and central macular thickness（CMT） exams were carried out at baseline（T0）and after 1（T1）,3（T3）,4（T4）,6（T6）,9（T9）,12（T12）,15（T15）,and 18mo（T18） post injection. RESULTS： Repeated measures ANOVA showed an effect of treatment on ETDRS（P〈0.0001）.Post hoc analyses revealed that ETDRS values were significantly increased at T1,T3,T4,T9,and T15（P 〈0.001） as compared to baseline value（T0）.At T6,T12,and T18,ETDRS values were still statistically higher than baseline（P〈0.001 vs T0）.However,at these time points,we observed a trend to return to baseline conditions.ANOVA also showed an effect of treatment（P 〈0.0001）.CMT decreased significantly at T1,T3,T4,T9,and T15（P〈0.001）.At T6（P〈0.01）,T12 and T18（P〈0.001） CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed.CONCLUSION： Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improveBCVA and CMT in DME patients resistant to anti-VEGF therapy.Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects.

Withdrawal of anti-tumour necrosis factor α therapy in inflammatory bowel disease

Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.

Role of Anti Angiogenic Therapy in Prevention of Recurrence in Hormonal Positive Breast Cancer: A Secondary Prevention Strategy and Method of Therapy

Existing literature supports the role of signaling protein vascular endothelial growth factor (VEGF) in tumor growth and metastasis and furthers its involvement in recurrence. In both experimental and clinical studies, VEGF has been shown to be a significant factor involved for aberrant blood vessel growth, and in fact is the target of several classes of antineoplastic drugs [1] [2] [3] [4]. That said, the current standard of care for estrogen receptor positive breast cancer (although improved over the last decade), has not provided a “meaningful preventive shift” since the discovery of angiogenesis and its role in induction of recurrence. In this article, we discuss an anti angiogenic therapy implementing natural compounds to inhibit the production of VEGF. We applied our preclinical data to justify the predicted effect on VEGF. We used liquid biopsy to monitor patients response to therapy as a surrogate for recurrence. We hypothesize that by inhibition of angiogenesis through this protocol, we are able to positively impact tumor recurrence. It is our experience that patients in our sample even with high recurrence scores (based on Oncotype Dx testing) had a major reduction in recurrence when estrogen blockers were combined with this protocol. We also propose longitudinal studies to compare outcomes with combinational therapies with estrogen blockers in highly expected to recur disease.

Changing common sense:Anti-platelet/coagulation therapy against cirrhosis

Until recently,anti-platelet/coagulation therapy had not been recommended for patients with cirrhosis.Although venous thrombosis is one of the representative complications of cirrhosis and ischemic disorders associated with atherosclerosis are not infrequent in cirrhotic patients,many clinicians have tended to hesitate to introduce anti-platelet/coagulation therapy to their patients.Undoubtedly,this is due to the increased risk of hemorrhagic diathesis in cirrhotic patients.However,accumulating evidence has revealed the benefits of anti-platelet/coagulation therapy for cirrhotic patients.In addition to the safety of the therapy carried out against cardiovascular diseases in cirrhotic patients,some clinical data have indicated its preventive effect on venous thrombosis.Moreover,the efficacy of antiplatelet/coagulation therapy against cirrhosis itself has been demonstrated both clinically and experimentally.The conceptual basis for application of anti-platelet/coagulation therapy against cirrhosis was constructed through two pathologic studies on intrahepatic thrombosis in cirrhotic livers.It may be better to use thrombopoietinreceptor agonists,which have been tested as a treatment for cirrhosis-related thrombocytopenia,in combination with anti-platelet drugs to reduce the risk of venous thrombosis.During the last decade,the World Journal of Gastroenterology,a sister journal of World Journal of Hepatology,has been one of the main platforms of active discussion of this theme.

Numerical simulation of inhibiting effects on solid tumour cells in anti-angiogenic therapy: application of coupled mathematical model of angiogenesis with tumour growth

To investigate the inhibiting effects of the anti-angiogenic factor andostatin and the anti-angiogenic drug endostatin on turnout angiogenesis and turnout cells, a coupled mathematical model of tumor angiogenesis with tumour growth and blood perfusion is developed. Simulation results show that angiostatin and endostatin can improve the abnormal microenvironment inside the tumour tissue by effectively inhibiting the process of tumor angiogenesis and decreasing tumour cells. The present model can be used as a valid theoretical method in the investigation of the tumour anti-angiogenic therapy.

Recovery rates of combination antibiotic therapy using in vitro microdialysis simulating in vivo conditions

Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20μg/mL and flow rate of 1.0μL/min had the best recovery. A concentration of 5.0μg/mL and flow rate of 1.0μL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.

Hemolysins of <i>Staphylococcus aureus</i>—An Update on Their Biology, Role in Pathogenesis and as Targets for Anti-Virulence Therapy

Staphylococcus aureus is a dangerous gram positive bacterial pathogen which, not only evades the host’s immune system but also can destroy the leucocytes especially neutrophils. It has an embodiment of virulence factors most of which are secreted. Staphylococcus aureus secretes a number of toxins which cause tissue damage and facilitate spreading and nutrients uptake. Among the toxins, hemolysins α, β, γ, δ and Panton Valentine Leukocidin (PVL) are unique that they drill pores in the membrane, leading to the efflux of vital molecules and metabolites. Hemolysins also help in the scavenging of iron, although many of them also have leucolytic properties. α-hemolysin, also known as α-toxin, is the most prominent cytotoxin which damages a wide range of host cells including epithelial cells, endothelial cells, erythrocytes, monocytes, keratinocytes and it damages cell membrane and induces apoptosis. β-Hemolysin significantly affects human immune cell function. It has Mg2+ dependent sphingomyelinase activity and degrades sphingomyelin of plasma membrane into phosphorylcholine and ceramides. The bi-component leukocidins, which include γ-hemolysin and PVL, attack human phagocytic cells and greatly contribute to immune evasion. Delta toxin is a low molecular weight exotoxin with a broad cytolytic activity. Virulence determinants, quorum sensing and biofilm synthesis provide some attractive targets for design and development of a new group of antimicrobial compounds. This review provides an update on the structure, biological functions of hemolysins and their role in quorum sensing/biofilm synthesis (if any) and as effective therapeutic targets for anti-virulence drug development. We have tried to bring together information available on various aspects of hemolysins and highlighted their distribution among all species of Staphylococcus and other bacteria. We have updated the status of development of candidate drugs targeting the hemolysins for anti-virulence therapy as it offers an additional strategy to reduce the severity of infection and which would, through quorum quenching, delay the development biofilms leading to drug resistance.

Anti-CD-20 Therapy in Refractory Adult Still’s Disease

Adult Still’s disease is a relatively rare form of rheumatoid arthritis with systemic inflammatory features. The prevalence is around 1.5 cases per 100,000 - 1000,000. In the current case we display a 30-year-old male patient with refractory adult still’s disease who suffered recurrent attacks of fever 39.5°C, arthritis in proximal interphalangeal joints (PIPs), wrists, tempromandibular joints (TMJs), knees and ankles, stitching chest pain, dyspnea, erythematous rash over the trunk, sore throat, weight loss (15 Kilograms in 4 months). The patients’ disease remained uncontrolled despite of synthetic disease modifying anti-rheumatic drugs and repeated intramuscular corticosteroid injections. Laboratory workup revealed erythrocyte sedimentation rate (ESR) of 95, C-reactive protein (CRP) of 100 mg/L, hemoglobin 10.5 gm%, leukocytosis 12,000/microlitre, mild elevation of liver function tests and dyslipidemia. Serology revealed negative rheumatoid factor, anti-nuclear antibody titre of 1:80, elevated serum ferritin 4000 micrograms/litre. The patient was started on rituximab (375 mg/m2), prednisolone 20 mg/day and selective Cox-2 inhibitor. Follow up for over three months following the completion of his pulse therapy, revealed no relapse of fever or fatigue, with morning stiffness of 5 - 10 minutes, VAS of 3, DAS28 of 3.8, HAQDI of 0.62, ESR 23, CRP 4.9, Hb 12.5 gm%, leucocytic count 9000/microlitre, the dose of prednisolone was successfully reduced to a dose of 5 mg/day orally. Conclusion: Anti-CD20 therapy successfully controlled systemic and articular refractory disease with sustained efficacy over a follow up period of up to 24 weeks.

Future options of anti-angiogenic cancer therapy

In human patients,drugs that block tumor vessel growth are widely used to treat a variety of cancer types.Many rigorous phase 3 clinical trials have demonstrated significant survival benefits;however,the addition of an anti-angiogenic component to conventional therapeutic modalities has generally produced modest survival benefits for cancer patients.Currently,it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human patients.In this article,we discuss possible mechanisms of various anti-angiogenic drugs and the future development of optimized treatment regimens.

Harnessing macrophages in thermal and non-thermal ablative therapies for urologic cancers-Potential for immunotherapy

Prostate and bladder cancers are one of the cancers occurring worldwide.In addition to radical surgery,the past decade has also focused on targeted therapy of overexpressed cancer proteins that are lethal and critical for cancer cell survival.However,targeted therapy cannot adapt for changing of cancer molecular characteristics and,ultimately,a clone that bypasses the targeted therapy emerges.This can be overcome by immunotherapy.New studies on ablative therapy of cancers show presence of immunomodulatory effect in these modalities.Tumor ablation prime the immune system for further destruction of persistent primary tumor in addition to destruction of concurrent metastatic disease and also reduce recurrence.Ablative therapies can achieve a state of increased antigenicity.Its combination with a novel macrophage targeted therapy may enhance immune priming,trafficking,and/or effector phases;thereby improving clinical outcomes.Tumor associated macrophages or M2 phenotype are now known to mediate this immunosuppressive pro-tumorigenic effect.Alteration of macrophage differentiation may enhance tumor destruction of ablative therapy.This breakthrough in immunotherapy opens up arenas for further robust clinical trials on combinatorial therapies.In the present review,we aim to elucidate the major aspects of immune stimulatory minimal invasive approaches by combining with macrophage directed pathways.

Factors That Influence Anti-Retroviral Therapy Adherence among Women in Lilongwe Urban Health Centres, Malawi

Introduction: Sub-SaharanAfricaremains most severely affected, with nearly1 inevery 20 adults (4.9%) living with HIV and this is accounting for 69% of the people worldwide. Although the regional prevalence of HIV infection is nearly 25 times higher in sub-Saharan Africa than in Asia, almost 5 million people are living with HIV in South, South-East and East Asia combined. Purpose: The purpose of this study was to find out the factors that influence anti-retroviral therapy adherence among women in Lilongwe Urban,Malawi. Methods: a descriptive cross-sectional design was used to study multi sites using quantitative methods. The sites were ART clinics at Area 18 health centre, and Area 25 health centre. A questionnaire was used to a convenient sample of 118 HIV positive women. Quantitative data from close-ended questions were coded and analyzed using the Statistical Package for Social Science (SPSS), version 16. Logistic regression model was used to execute the potential covariates. Findings: ART adherence among women is influenced by knowledge levels on: perceived importance and consequences for not adhering to ART;Short waiting time;good relationships with the next of kin and service providers;trust and effective coping mechanisms to stressful events. Source of information was highly associated with adherence in the logistic regression OR ≤ 2.89;CI (1.66 ± 5.38);p (0.039). Moreover, Short waiting time of the women at the hospital during the ARV refill period is highly associated with ART adherence level OR ≤ 4.11;CI (2.05 ± 6.12);p (0.021). On the other hand, factors that contribute to non-adherence are reduced knowledge level p0.002;Side effects of ART;bad relationships with service providers and relationship with the next of kin as well as occupation of the clients (women). Conclusion: Despite stressful events to HIV positive living women, this study revealed that the majority of these participants would continue taking ART if the factors are very minimal. Encouraging the women who stop taking ART particularly in urban health centres due to such factors like religious beliefs that God is superior and will heal them would influence the ART survival rate in Malawi.

New Developments in Anti-Anginal Therapy: Roles of Ivabradine, Allopurinol and of Agents Modifying Myocardial Metabolism

Over the last 20 years, it has emerged that, while surgical revascularisation of extensive ischaemic heart disease may have prognostic advantages, the main issues considered regarding individual management are usually those of symptomatic improvement only. The major impetus towards invasive intervention is therefore failure of prophylactic anti-anginal therapy. On the other hand, many patients, especially the elderly, now present the clinical problem of ongoing angina without residual invasive options. There is an ongoing need for more effective anti-anginal therapies. Of the currently available major classes of prophylactic anti-anginal agents, neither nitrates, β-blockers nor calcium antagonists generally produce marked improvements in exercise duration. Three areas of new therapeutic development in anti-anginal therapy are worthy of note. These involve the sinus node inhibitor ivabradine, high dose allopurinol (xanthine oxidase inhibitor) and a new class of “metabolic modulators” represented by perhexiline, trimetazidine and probably ranolazine. The current review addresses the therapeutic potential of these agents. Notably, all of these “new” drugs are potentially suitable for management of angina in the setting of impaired left ventricular systolic function, and they may also be utilized in patients with angina independent of the presence of coronary disease (for example in hypertrophic cardiomyopathy). The current evidence for efficacy and potential future development in this area are reviewed.