Months Of Combination Therapy Research Articles

Combination of oral zinc gluconate and topical triclosan: An anti-inflammatory treatment modality for initial hidradenitis suppurativa

BackgroundHidradenitis suppurativa (HS) is often a therapeutic challenge with relapses and chronicity which can severely impact patients’ quality of life. ObjectiveTo evaluate the efficacy of anti-inflammatory oral zinc gluconate, 90mg/day, combined with topical triclosan, 2% twice daily. MethodsWe retrospectively evaluated the medical records of HS patients in our HS Center of the Department of Dermatology, Venereology, and Allergology, Ruhr-University Bochum, regarding change of disease severity and quality of life. Secondary outcome measures were the number of nodules and fistulas, the number of boils or flair-ups, and the intensity of pain. ResultsSixty-six patients in Hurley stage I and II were included. After 3 months of combination therapy, the modified HS Score and the Dermatology Life Quality Index improved significantly (p<0.0001 and p=0.0386, respectively). The number of inflammatory nodules, new boils or flare-ups, and erythema scores decreased significantly. Fistula count and the visual analogue scale score showed no significant difference. Side-effects (mostly abdominal pain and nausea) were reported by 12 (22.2%) patients. ConclusionThe combination therapy of zinc gluconate and topical triclosan can be considered as an anti-inflammatory treatment for HS patients in Hurley stage I and initial Hurley stage II.

Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity

AbstractIdelalisib is a small-molecule inhibitor of PI3Kδ with demonstrated efficacy for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as front-line therapy, we enrolled 24 subjects in a phase 2 study consisting of 2 months of idelalisib monotherapy followed by 6 months of combination therapy with idelalisib and the anti-CD20 antibody ofatumumab. After a median follow-up period of 14.7 months, hepatotoxicity was found to be a frequent and often severe adverse event. A total of 19 subjects (79%) experienced either grade ≥1 ALT or AST elevation during the study, and 13 subjects (54%) experienced grade ≥3 transaminitis. The median time to development of transaminitis was 28 days, occurring before ofatumumab introduction. Younger age and mutated immunoglobulin heavy chain status were significant risk factors for the development of hepatotoxicity. Multiple lines of evidence suggest that this hepatotoxicity was immune mediated. A lymphocytic infiltrate was seen on liver biopsy specimens taken from 2 subjects with transaminitis, and levels of the proinflammatory cytokines CCL-3 and CCL-4 were higher in subjects experiencing hepatotoxicity. All cases of transaminitis resolved either by holding the drug, initiating immunosuppressants, or both, and rates of recurrent toxicity were lower in patients taking steroids when idelalisib was reinitiated. A decrease in peripheral blood regulatory T cells was seen in patients experiencing toxicity on therapy, which is consistent with an immune-mediated mechanism. These results suggest that caution should be taken as drugs within this class are developed for CLL, particularly in younger patients who have not received prior disease-specific therapy. This study was registered at www.clinicaltrials.gov as #NCT02135133.

PTU-049 Concurrent Immunomodulator Therapy does not Influence Infliximab or Adalimumab Trough Levels During Maintenance Therapy

Introduction Combination therapy with infliximab (IFX) and immunomodulators (IM) is superior to monotherapy showing better outcomes at 1 year for Crohn’s disease 1 and UC. 2 Withdrawal of IM after 6 months of combination therapy has been shown not to adversely affect clinical outcomes though patients on concurrent thiopurine have higher trough levels and lower CRP. 3 The role of concomitant IM therapy is unclear for patients treated with adalimumab (ADA). We aimed to evaluate the impact of concomitant IM therapy on trough levels of IFX and ADA. Methods We conducted a retrospective observational study of all IBD patients on maintenance therapy who had had IFX and ADA trough levels measured between Jan13-Jan16. Testing was undertaken at the discretion of the treating clinician. Clinical information including duration of disease, site of disease, duration of anti-TNF therapy, IM therapy, smoking status, prior anti-TNF exposure, and disease activity was recorded. Drug level and anti-drug antibody measurements were performed on sera using the Lisa-Tracker IFX and ADA ELISA kit (Theradiag, France). Pairwise comparison of means was used to compare trough levels in patients with and without concomitant IM therapy. A multivariate logistic regression was used to correct for confounders and the impact on antibody formation assessed with Fishers exact test. Results 200 patients (120 IFX and 80 ADA) were included. 65.8% of IFX and 55% of ADA patients were on concurrent IM therapy. Mean ADA trough levels among patients on concurrent IM was 6.72±1.91µg/ml whilst patients not on concurrent IM had levels of 5.16±2.88 µg/ml(p = 0.005). This difference was not significant after adjustment for dose escalation. 23 patients (28.7%) were on weekly dosing whereas 57 (71.2%) were on alternate weeks. The mean trough level in patients on IM was 4.01±3.52 and not on IM was 3.96±2.83(p = 0.9). Thirty patients had positive antibodies and trough levels were 1.25±2.1µg/ml compared to 4.91±3.1µg/ml(p Conclusion Trough levels of IFX and ADA were not significantly different among maintenance patients with and without concomitant IM therapy. Surprisingly, the immunogenicity of IFX was not impacted by concurrent IM. References 1 Ruffolo C, et al . Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 2010; 363 :1086–8. 2 Panaccione R, et al . Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology 2014; 146 :392–400. 3 Drobne D, et al . Withdrawal of immunomodulators after co-treatment does not reduce trough level of infliximab in patients with crohn’s disease. Clin Gastroenterol Hepatol 2015; 13 :514–21. Disclosure of Interest None Declared

Lamivudine-resistant rtL180M and rtM204I/V are persistently dominant during combination rescue therapy with entecavir and adefovir for hepatitis B.

Adefovir (ADV) sequential monotherapy was included in the 2005 Asia-Pacific guidelines for the management of patients with lamivudine (LAM) resistance. However, following the development of ADV resistance, the proportion of resistant variants during combined rescue therapy with ADV and entecavir (ETV) were unknown. The present study characterized the dynamics of resistant variants in patients with chronic hepatitis B (CHB) and LAM-resistant variants during antiviral therapy consisting of ADV monotherapy followed by ADV-ETV combination therapy. A total of 3 patients were selected from a cohort of 55 patients with CHB due to developing ADV resistance. The patients had been previously treated with LAM (100 mg daily) for 21–24 months. At the initiation of sequential monotherapy with ADV, LAM-resistant variants (rtM204V/I and rtL180M) were detected in the three patients. These patients developed ADV resistance during 19–30 months of ADV sequential monotherapy, and then switched their antiviral regimen to ADV-ETV combination therapy. During ADV monotherapy and ADV-ETV combination therapy, the patients were monitored every 3 months for the first year of therapy, and then every 6 months thereafter. A total of 30 serum samples were collected from the patients throughout the monitoring period. In total, 10 mutants that were associated with commonly-used antiviral drugs were detected by pyrosequencing. During ADV sequential monotherapy, LAM-resistant variants were gradually decreased, whereas ADV-resistant rtA181V/T and rtN236T variants gradually increased in the viral population. During 30–41 months of ADV-ETV combination therapy, viral load reduction was 2.59–3.28 log10 copies/ml; ADV-resistant variants rtA181T/V and rtN236T were undetectable following 11–24 months of combination therapy; and rtL180M and rtM204I/V remained dominant in the viral population. In conclusion, the results of the present study suggested that, in patients with LAM and ADV-resistant variants that developed during LAM-ADV sequential monotherapy, ETV-ADV combination therapy may partially inhibit the replication of HBV DNA; however, LAM-resistant rtL180M and rtM204I/V variants remained predominant following 30–41 months combination therapy.

SHORT-TERM IMPACT OF A COMBINED NUTRACEUTICAL ON COGNITIVE FUNCTION, PERCEIVED STRESS AND DEPRESSION IN YOUNG ELDERLY WITH COGNITIVE IMPAIRMENT: A PILOT, DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

Background: The prevalence of senile dementia is increasing worldwide, especially in the developed countries. Nevertheless, drug therapy isn’t often enough to treat this condition. Researchers are evaluating the possible impact of a preventive approach, based on an improvement of lifestyle and the intake of micronutrients. Moreover, there is an increasing interest for combined nutraceuticals that can act as memory and learning enhancers, with a significant and beneficial potential on the cognitive disorders. Objective: To evaluate the effects of a rational assemblage of nutraceuticals on cognitive functions in a sample of 30 elderly subjects. Design: Double bind, cross-over designed trial versus placebo Setting: outpatient clinical practice Participants: 30 elderly subjects with basal Mini-Mental State Examination score between 20 and 27 and self-perceived cognitive decline. Intervention: Treatment with a combination of nutraceuticals based on Bacopa monnieri, L-theanine, Crocus sativus, copper, folate and vitamins of B and D group. After2 months of treatment or placebo. Measurements: Patients were evaluated with Mini-Mental State Examination (MMSE), Perceived Stress Questionnaire (PSQ) and Index and Self-Rating Depression Scale (SRDS). Results: MMSE and PSQ Index significantly improved in the active treatment arm, both versus baseline and versus the parallel arm. Both groups experienced a significant improving in the SRDS scores. Conclusions: We obtained a good and significant improvement of the cognitive functions tested with the MMSE, PSQ-Index and SRDS score, after 2 months of combined therapy of nutraceuticals. Further confirmation will be needed to verify these observations on the middle and long term in a larger number of subjects.

Surgery for brain tuberculosis: a review.

The two main manifestations of brain tuberculosis that require surgery are hydrocephalus associated with tuberculous meningitis (TBMH) and brain tuberculomas. TBMH most often responds to medical therapy but surgery is required promptly for those who fail medical therapy. Both ventriculoperitoneal (VP) shunt and endoscopic third ventriculostomy (ETV) are valid options although the latter is more often successful in patients with chronic hydrocephalus than in those with acute meningitis. Patients with TBMH are more prone to complications following VP shunt than other patients. The outcome of these patients is determined by the Vellore grade (I to IV) of the patients prior to surgery with those in good grades (I and II) having a better outcome and those in the worst grade (IV) having a high mortality in excess of 80 %. Patients with brain tuberculomas present clinically with features of a brain mass, indistinguishable clinically from other pathologies. CT and MR features might provide a probable diagnosis of a tuberculoma but most often a histological diagnosis is desirable. Empiric medical therapy is reserved for a small number of patients. Although the treatment of brain tuberculomas is essentially medical, surgery is required when the diagnosis is in doubt, to reduce raised intracranial pressure or local mass effect and to obtain tissue for culture and sensitivity studies. Stereotactic biopsy, stereotactic craniotomy and excision of superficial small tuberculomas and microsurgery are all procedures used to manage brain tuberculomas. The outcome in patients with brain tuberculomas is good if the tuberculous bacillus is sensitive to the anti-tuberculous therapy. The duration of therapy is debated but we suggest at least 18 months of combination therapy with three or four anti-tuberculous drugs and continue the therapy till the tuberculoma has resolved on neuro-imaging.

Identification of mutations in the HVR1 and PKR-BD regions in HCV-infected patients resistant to PEG-IFNα/RBV therapy.

The identification of mutations in the HVR1 region of hepatitis type C virus (HCV) is time-consuming and expensive, and there is a need for a rapid, inexpensive method of screening for these mutations to predict the ineffectiveness of pegylated interferon alpha combined with ribavirin (PEG-IFNα/RBV) therapy. The project was designed to evaluate the usefulness of the high resolution melting (HRM) technique to screen for mutation in the cDNAs encoding the HVR1 and protein kinase R-binding domain (PKR-BD) regions in a group of 36 patients infected with HCV and resistant to 12 months of combined therapy with PEG-IFNα/RBV. Viral RNA was isolated, reverse transcribed, and the fragments encoding the HVR1 and PKR-BD regions were polymerase chain reaction (PCR)-amplified, cloned, sequenced, and the melting profiles and the melting temperature (Tm) were determined by the HRM technique. After the treatment, the melting profiles of HVR1 cDNAs revealed a dominant peak corresponding to the Tm of about 85 °C (HCVs85) in almost all patients. One or more minor peaks were also observed, indicating the existence of cDNA(s) of different Tm. The HMR analysis suggested four typical forms of response to treatment. These suppositions were supported by sequencing. The HRM analysis revealed no changes in the melting profiles of PKR-BD cDNAs in the same patient before and after the therapy, suggesting that, within 12 months of treatment, new mutations were not introduced in PKR-BD. These findings were substantiated by sequencing. The HRM technique can be applied for the rapid screening for mutations in the cDNAs encoding the HVR and PKR-BD regions of HCV. We suggest that the detection of HCVs85 peak before the IFNα/RBV therapy might predict the ineffectiveness of treatment.

Factors Predicting Therapeutic Efficacy of Combination Treatment With Sitagliptin and Insulin in Type 2 Diabetic Patients: The ASSIST-K Study.

BackgroundIt is unclear whether dipeptidyl peptidase-4 inhibitors decrease hemoglobin A1c (HbA1c) in a glucose-dependent manner in patients on insulin therapy who have impaired insulin secretion. This study investigated factors influencing the efficacy of sitagliptin when used concomitantly with insulin to treat type 2 diabetes mellitus (T2DM) in the real-world setting.MethodsA retrospective study was conducted of 1,004 T2DM patients at 36 Japanese clinics associated with the Diabetes Task Force of the Kanagawa Physicians Association. Eligible patients had been on insulin for at least 6 months, with a baseline HbA1c of 7.0% (53 mmol/mol) or higher. Baseline characteristics and laboratory data from 495 patients were subjected to multiple regression analysis to identify factors influencing the change of HbA1c.ResultsMost patients (n = 809) received sitagliptin at a dose of 50 mg. In the 1,004 patients, HbA1c decreased by 0.74% (6 mmol/mol) and body weight increased by 0.1 kg after 6 months of combination therapy. Multiple regression analysis showed that a higher baseline HbA1c, older age, and lower body mass index influenced the change of HbA1c after 6 months. Hypoglycemic symptoms occurred in 7.4%, but none were severe.ConclusionsThese results emphasize the importance of a higher HbA1c at the commencement of sitagliptin therapy in patients on insulin. Glucose-dependent suppression of glucagon secretion by sitagliptin may be useful in patients with impaired insulin secretion. Sitagliptin can be used concomitantly with insulin irrespective of the insulin regimen, duration of insulin treatment, and concomitant medications.

Significance of intraprostatic architecture and regrowth velocity for considering discontinuation of dutasteride after combination therapy with an alpha blocker: a prospective, pilot study.

PurposeWe conducted a prospective single-center study to evaluate the possibility of discontinuation of dutasteride after combination therapy with an alpha blocker for benign prostatic hyperplasia (BPH).Materials and MethodsWe prospectively treated BPH patients with an alpha blocker and dutasteride (0.5 mg/d). Patients who had been treated with alpha blockers against BPH for more than 2 months were eligible, and 20 patients were included in the study. After 6 months of combination therapy, dutasteride was discontinued. Patients were followed for 12 months after cessation. Prostate volume, intraprostatic architecture determined by transrectal ultrasound, peak urinary flow rate, postvoid residual urine volume, and the serum prostate-specific antigen level were evaluated every 6 months, and the International Prostate Symptom Score and overactive bladder symptom score (OABSS) every 3 months. Patients were allowed to restart dutasteride during the follow-up period according to their desire.ResultsTwelve patients (12/20, 60%) restarted the combination therapy from 6 to 12 months into the follow-up period. For patients who restarted dutasteride, the prostate volume and OABSS had increased and worsened after discontinuation, respectively. A visible transition zone with a clear border on transrectal ultrasound at baseline and regrowth of the prostate after discontinuation of dutasteride were risk factors for restarting the therapy (Mann-Whitney U test: p=0.008, p=0.017).ConclusionsProstatic enlargement after discontinuation of dutasteride differs among patients. Rapid regrowth of the prostate leads to deterioration of storage symptoms and a tendency to restart dutasteride. Baseline intraprostatic architecture may be a predictive factor for whether the patient is a good candidate for discontinuation.

Presumed tuberculous choroiditis: Unusual presentation and review of the literature

This is a report of a 35-year-old female who was managed as a case of presumed tuberculous choroiditis. She presented with bilateral serpiginous choroiditis which failed to heal despite 3 months of combination therapy with steroids and immunosuppressive medications; however, the lesions successfully healed after initiation of anti-tuberculous agents and stoppage of immunosuppressive agents. The association represent underlying tuberculosis in the aetiopathogenesis of serpiginous choroiditis. This report also highlights the importance of a detailed systemic and laboratory evaluation of patients presenting with serpiginous choroiditis.

A Novel Immunomodulatory Treatment Involving Mycophenolate Mofetil and Corticosteroids for Pediatric Autoimmune Cytopenias

Background: Autoimmune cytopenias are defined by immune-mediated destruction of distinct hematopoietic lineages, including white blood cells, red blood cells, and platelets. The destruction of a single lineage in response to an unknown stimulus is known as a primary or idiopathic autoimmune cytopenia. These include immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN). The primary treatment modality for all autoimmune cytopenias are drugs that suppress or modulate the immune system. Typically first-line treatment involves the use of corticosteroids. However, this treatment modality often requires prolonged use of steroids, which impacts the quality of life of affected patients and causes multiple adverse side effects. For the treatment of pediatric autoimmune cytopenias, the goal of therapy is to modulate the immune system and hence stabilize counts, while also preventing adverse side effects secondary to medications. Mycophenolate mofetil (MMF) is an immunosuppressive drug that inhibits lymphocyte proliferation and limits the mobilization of leukocytes to sites of inflammation. Here, we propose a novel combination therapy of MMF, an adjunct immunosuppressive, and corticosteroids. This combination may allow for rapid decrease of steroid usage as well as prolonged count stabilization in pediatric patients with autoimmune cytopenias.Objective: To evaluate the efficacy of Mycophenolate mofetil and corticosteroids as a novel combination therapy for stabilizing counts and rapid weaning of steroid usage in pediatric patients with autoimmune cytopenias.Design/Method: Prospective case series of 5 patients, 4 with AIHA and 1 with ITP, between the ages of 2 and 16 that are being treated with the combination therapy of corticosteroids and MMF.Results: All patients (Patients 1-4 with AIHA and Patient 5 with ITP) reached minimal to no corticosteroid use after a few months of being on combination therapy, as seen in Figure 1. Patient 1 sustained Hgb levels above 13g/dl after 20 days of combination therapy and an improvement in IgG mediated AIHA, with a decrease in titers from 4+ to 2+ after five months of therapy. In addition, Patient 1 had a decrease in reticulocyte counts from 21.4% to 0.2% after five months of therapy, as well as a decrease in LDH levels from 714 IU/L to 551 IU/L after two months of therapy. Patient 2 sustained Hgb levels above 13g/dl after one month of combination therapy as well as a normal reticulocyte count of 0.8%. Patient 3 has been on combination therapy for one month and has improved Hgb levels from 11g/dl to 11.4g/dl as well as had a significant reduction in steroid usage. Patient 4 sustained Hgb levels above 12g/dl after six months of combination therapy, an improvement in IgG mediated AIHA, with a decrease in titers from 4+ to 3+ after 16 months of therapy, and a decrease in reticulocyte counts from 43.2% to less than 2% after 12 months of therapy. Patient 5 with ITP had a marked increase in platelet counts from 9k/μl to 418k/μl after only 8 days of combination therapy and has maintained normal platelet counts thereafter. All patients have rapidly decreased steroid doses, maintained targeted MMF doses without toxicities or secondary infections, and not had recurrences of autoimmune cytopenias.Conclusions: Mycophenolate mofetil has been utilized as an adjunct immunosuppressive in a small number of autoimmune diseases and for the treatment of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. Never before has the combination of MMF and corticosteroids been used to treat pediatric patients with autoimmune cytopenias. The novel combination of MMF and corticosteroids may be an optimal treatment option for pediatric patients with autoimmune cytopenias such as AIHA and ITP. This unique combination of high dose steroids with rapid weaning, coupled with the continued use of MMF mediated immunosuppression allows for prolonged count stabilization with minimal adverse side effects. [Display omitted] *Patient 1’s baseline total daily dose of prednisone is 120mg at time 0 months DisclosuresOff Label Use: Mycophenalate mofetil is an immunosuppressive medication initially utilized in transplantation medicine, and now has been used in a variety of autoimmune diseases. .

Combined Therapy with Peritoneal Dialysis and Hemodialysis: A Multicenter Retrospective Observational Cohort Study in Japan

Background/Aims: Combining peritoneal dialysis (PD) and hemodialysis (HD) has been common treatment option in Japan. Methods: In this retrospective, multicenter, observational study, the clinical characteristics and outcomes of 104 patients (57 w 11 years, males 72%) who had switched from PD alone to combined therapy with PD and HD were studied. Clinical parameters were measured at baseline and after 3 months of combined therapy. Results: At baseline, urine volume, dialysate-to-plasma ratio of creatinine (D/P Cr), and total Kt/V were 150 ml/day (range: 0-2,000 ml/day), 0.67 w 0.11, and 1.8 w 0.4, respectively. During the first 3 months of combined therapy, body weight, urine volume, serum creatinine level, and D/P Cr decreased, whereas hemoglobin levels increased. Conclusions: In patients where PD does not result in acceptable outcomes, combined therapy with PD and HD may have potential benefits in terms of dialysis adequacy and hydration status. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=368389 i 2014 S. Karger AG, Basel

Effect of Telmisartan on Heart Failure in Patient with Hypertensive Cardiomyopathy

A 58-year-old man was referred to our hospital because of acute heart failure. He was diagnosed as hypertensive cardiomyopathy, and started treatment of heart failure and hypertension. After 6 months of combination therapy, we modified the treatment, and started telmisartan, then, follow-up examination of standard ECG-gated SPECT imaging was done. The SPECT data were reanalyzed by using new software, heart function view (Medi-Physics Co.), automatically. LVEF were used as markers of systolic function, and Peak phase, systolic phase standard deviation (Phase SD) and histogram bandwidth (Bandwidth) were used as markers of dyssynchrony. We also tested BNP concentration as a marker of heart failure. As shown in figure, telmisartan may have had favourable effects on heart failure in this case.Tabled 1TreatmentLVEF (%)EDV (ml)Peak Phase (°)Phase SD (°)Bandwidth (°)BNP (pg/ml)Pre-treatment (amlodipine 2.5mg)25.423114552.3181302amlodipine 2.5mgcarvedilol 2.5mg35.321112962.218334.3losartan 25mgperindopril 2mgamlodipine 2.5mg45.314113617.16813.6carvedilol 2.5mg50.211212917.16610telmisartan 40mg53.213913513.3494.8 Open table in a new tab

Comparison of visual outcomes between intravitreal ranibizumab injection combined with or without photodynamic therapy for polypoidal choroidal vasculopathy

Objective To compare the visual outcomes of treatment with intravitreal ranibizumab alone or in combination with photodynamic therapy (PDT) in patients with polypoidal choroidal vasculopathy (PCV).Methods In this retrospective and comparative study,36 eyes of 36 patients with PCV were enrolled.Eighteen eyes received 0.5 mg (0.05 ml) ranibizumab injection only (simple injection group) and the other 18 eyes underwent combination therapy of ranibizumab injection and PDT (combination treatment group).Intravitreal ranibizumab was given at the third day after PDT.Re-treatment was considered in clinic examination.The minimum re-treatment interval was 3 months for combination therapy and 1 month for ranibizumab.Best corrected visual acuity (BCVA) of logarithm of the minimum angle of resolution (logMAR) at baseline and each follow-up visit at 1,3,6,12 month was measured as a primary outcome,and complications also observed in every follow-up.Results No complications occurred in these 36 patients during the treatment or follow-up,such as retinal detachment,sustained high intraocular pressure,retinal holes,intraocular inflammation,and systemic adverse reactions.The average times of ranibizumab injections of simple injection group and combined treatment group were (3.00 ± 0.84) and (1.89±0.68) times respective,and the difference was significant (t=4.370,P=0.000).The logMAR BCVA of the first and third month after initial treatment between two groups were significant different (t=0.668,0.940; P＞0.05).However,there was no significant difference between them at the 6th and 12th month (t=2.188,2.547; P＜0.05).In the last follow-up,the logMAR BCVA were improved in simple injection group and combination treatment group compared to the pre-treatment values (t =3.351,9.408; P=0.012,0.000).In simple injection group,visual acuity was improved in 3 eyes (16.7％),stable in 13 eyes (72.2％) and decreased in 2 eyes (11.1％).In combination treatment group,visual acuity was improved in 4 eyes (22.2％),stable in 13 eyes (72.2％) and decreased in 1 eyes (5.6％).Conclusions Intravitreal ranibizumab injection and combined with PDT are both effective to improve vision in patients with PCV.Visual acuity was the same between the two treatments in 3 months after initial treatment; however 6 to 12 months after first treatment,patients received PDT combined with intravitreal ranibizumab injection had better visual acuity than those received the intravitreal ranibizumab injection only. Key words: Choroid diseases/therapy; Photochemotherapy; Antibodies, monoclonal; Comparative effectiveness research

Disseminated Abdominal Hydatidosis: A Rare Presentation of Common Infectious Disease

Hydatid disease is one of the most geographically widespread zoonoses with substantial disease burden. In this report we are discussing an unusual case of intra-abdominal HD that was ongoing for 22 years despite two surgical interventions. Significant symptomatic relief was achieved within the first two months of combination therapy with albendazole and praziquantel. HD is still of public health concern in the Middle East that needs optimized care.

Laboratory Correlates and a Phase I Clinical Trial Of Lenalidomide In Combination With Plerixafor In Patients With Previously Treated Chronic Lymphocytic Leukemia

The microenvironment emerged as an attractive therapeutic target for chronic lymphocytic leukemia (CLL) given increasing evidence of its essential role in CLL cell survival. Plerixafor, a small molecule inhibitor of the CXCR4 receptor, is responsible for homing CLL to the microenvironment via a concentration gradient of its cognate ligand CXCL12 and has been safely tested in CLL patients. Lenalidomide is an immunomodulatory small molecule with efficacy in CLL, though monotherapy responses are typically partial and delayed. The combination of plerixafor with lenalidomide offers a novel non-cytotoxic alternative to improve clinical activity. Laboratory correlatives were designed to improve understanding of the effects of individual and combination therapy on the biology of CLL, assess for CLL mobilization from the microenvironment, and discover targetable drug resistance mechanisms to improve therapeutic efficacy. [Display omitted] In this single institution phase I clinical trial, subjects were dose escalated on lenalidomide before initiation of plerixafor (Fig. 1). Primary safety response assessment was after one month of combination therapy. After four cycles of combination therapy, the primary response assessment was performed. Peripheral blood was collected for correlates and included an extended CLL phenotype panel (CLL cell-surface markers, CD184/CXCR4, sIgM, CD38, CD40, CD52, CD80, CD86, CD95) by flow cytometry with analysis of CLL subpopulations by CXCR4 expression levels. Phosphoprotein analysis was performed by phosphor-flow cytometry (phosflow).Fifteen subjects were enrolled with 10 subjects initiating plerixafor. Subjects included 4 females with a median 62 years of age and 4 prior lines of therapy. Two dose limiting toxicities (neutropenia, thrombocytopenia) occurred in plerixafor dose level two. Four patients reached primary response assessment. One patient had a PR and three patients had SD, however, all assessed patients derived improvement in nodal mass and disease symptoms. Phenotyping demonstrated a statistically significant decrease in CD20 and an increase in CD40 and CD95 for subjects initiating plerixafor. For the four subjects completing to end of study (EOS), the statistically significant decline in CD20 continued and CD95 and CD52 declined significantly. In all subjects, the proportion of CLL expressing high CD184/CXCR4 decreased significantly by four hours after plerixafor administration (Fig. 2). Phosflow for subjects initiating plerixafor revealed significant increases in phosphorylation of p-Akt, p-Mek, and p-Erk with decreases after plerixafor addition. For subjects reaching EOS, there was a significant decline in p-Syk from time of plerixafor addition but an increase in p-Akt. [Display omitted] Lenalidomide plus plerixafor is a novel non-cytotoxic therapeutic alternative with an acceptable safety profile in heavily pretreated CLL patients. Grade 3/4 toxicities (and DLTs) were predominantly related to myelosuppression. Though the study is ongoing, the first two patients of cohort 3 have reached safety response assessment without a DLT; therefore a minimum total of 5 subjects were safely treated at dose level one (plerixafor 0.24mg/kg) and it was identified as the MTD. Plans are to proceed to a phase II trial to evaluate efficacy. Early responses among patients able to escalate lenalidomide to 10mg target dose are encouraging given the duration subjects remained on trial without progression. Correlates support mobilization of CLL from the microenvironment with decreases in CXCR4 expression and downstream signaling. Increases of CD40, CD80 and CD86 on lenalidomide monotherapy suggest immunomodulatory actions. Ongoing study will confirm observed trends, and improve understanding of response and resistance mechanisms for translation into optimized treatment strategies. Disclosures:Brander:Celgene: Research Funding, Research Fund provided to lab but not author Other. Off Label Use: Lenalidomide and Plerixafor are being studied in this Phase I clinical trial but have not been FDA approved for the indication of CLL. Allgood:Celgene: Research Funding. Lanasa:Celgene: Research Funding.

Combining Incretin-Based Therapies With Insulin

### What is the rationale for adding incretin-based therapies to insulin? The combination of the incretin-based therapies, i.e., the dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 receptor agonists (GLP-1RAs), with basal insulin has, in theory, logical appeal. While basal insulin primarily improves fasting plasma glucose (FPG) control, the glucose-dependent effect of incretins will additionally benefit postprandial plasma glucose (PPG) control. This should enable improved control of A1C with the expectation of relatively stable blood glucose concentrations, and the combination of incretins with basal insulin might reduce insulin dose requirement and, consequently, weight gain. This also supports the concept that combining the incretin-based therapies with basal insulin should enable tight glycemic control with a low risk of hypoglycemia. Furthermore, a reciprocal benefit of this combination is that the basal insulin will theoretically supplement endogenous insulin production and “rest” the β-cell, enabling greater recovery of the endogenous insulin response when required. The basis of this theory is formed from research showing benefits with incretin therapies for β-cell function (1) and β-cell mass in experimental systems (2–4). In addition to their antihyperglycemic properties, GLP-1RAs also reduce gastrointestinal motility, which, together with increased satiety, produces a weight-sparing effect (2). This quality could mitigate the weight gain associated with insulin therapy and might be further enhanced through any reductions in insulin dose. ### Evidence to date: how do the data from insulin plus incretin clinical studies meet with expectations? #### Glycemic control. Using basal insulin to reduce FPG is an effective way of improving glycemic control; however, the second component of glycemic control, PPG, requires additional consideration. This is one area where incretin-based therapies and basal insulin should have complementary actions. ##### Adding incretin-based therapies to insulin. In an uncontrolled, retrospective investigation involving a cohort of 188 patients receiving insulin, the addition of exenatide produced an A1C reduction of –0.66% ( P < 0.001) from a baseline value of 8.05% after 6 months of combination therapy—an improvement that was maintained at 27 months (5). Moreover, the patients in this …

Successful treatment of chronic hepatitis B and D with pegylated-interferon plus entecavir

Interferon-based regimen has been used to treat hepatitis D virus (HDV) super-infection on top of hepatitis B virus (HBV) carriers; however, viral relapse is frequent after stopping therapy. Recently, quantitative hepatitis B surface antigen (qHBsAg) was introduced to help the management of chronic hepatitis B (CHB). Little is known about its role in the treatment of HBV and HDV dual infection. Herein, we reported a 45-year-old male HBV carrier with HDV co-infection who received combination therapy of pegylated-interferon α-2a plus entecavir. The qHBsAg level was adopted as the treatment guidance and a consolidation therapy of 12 months was continued after HBsAg loss. The patient achieved HBsAg seroconversion with HDV RNA undetectable after 35 months of combination therapy and sustained therapeutic response 12 months post-therapy. Therefore, personalized response-guided therapy by using qHBsAg may be an option for the treatment for HBV and HDV dual infection.

Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice

AimTo evaluate the efficacy and safety of Entecavir (ETV) plus adefovir (ADV) for chronic hepatitis B (CHB) patients after multiple nucleos(t)ide analogue (NAs) failure treatment.MethodsHepatitis B e antigen (HBeAg)-positive patients who had a suboptimal response or developed resistance to two or more previous NAs treatments were included, and all subjects were treated with ETV in combination with ADV for ≥ 24 months. Complete virologic response (CVR) was defined as an undetectability of serum hepatitis B virus (HBV) DNA level during treatment. Safety assessment was based on the increasing of serum creatinine and creatine kinase levels.ResultsA total of 45 eligible patients were included. Twenty-five patients had been treated with lamivudine (LAM) or telbivudine (LdT) and developed genotypic resistance. Resistance to ADV was present in 18 patients and 4 patients had a suboptimal response to ETV. Two patients had a resistance to both LAM and ADV. The cumulative probabilities of CVR at 12 and 24 months of ETV + ADV treatment were 88.9% (40/45) and 97.8% (44/45), respectively. Although one patient failed to achieve CVR, its serum HBV DNA level decreased by 3.3 log copies/mL after 24 months of combination therapy. The cumulative probability of HBeAg seroconversion was 15.6% (7/45) and 26.7% (12/45) at 12 and 24 months of treatment, respectively. History of prior exposure to specific NAs did not make a difference to ETV + ADV treatment outcome. There were no significant adverse events related to ETV + ADV therapy observed in the study subjects.ConclusionETV + ADV can be used as an effective and safe rescue therapy in patients after multiple NA therapy failures, especially in the areas where tenofovir is not yet available.

Metastatic ACTH-producing pituitary carcinoma managed with combination pasireotide and bevacizumab following failure of temozolamide therapy: A case report.

e13022 Background: ACTH-producing pituitary carcinomas (APPC) are malignant neuroendocrine tumors affecting the adenohypophysis. They are extremely rare, with a poor prognosis. They are poorly responsive to chemotherapy and radiotherapy. We report the case of a 25 year old female with a diagnosis of APPC, metastatic to bone, treated with temozolamide, followed by bevacizumab and the novel agent, pasireotide. Methods: The patient was diagnosed in 2002 with an ACTH-secreting pituitary macroadenoma causing Cushing’s disease. Despite two transphenoidal surgeries, bilateral adrenalectomies, craniotomy with excision of pituitary fossa tumour and radiotherapy she developed aggressive Nelson’s Syndrome. Following discontinuation of a somatostatin analogue in 2009 her ACTH levels rose dramatically causing progressive skin hyperpigmentation. Her disease continued to progress despite CyberKnife treatment. She was referred for temozolamide chemotherapy for treatment of the pituitary adenoma. At review, she had severe back pain. Investigations suggested metastatic disease and biopsy confirmed a diagnosis of metastatic APPC to bone.We commenced treatment with Temozolamide, however her disease progressed – ACTH levels were &gt;200,000pmol/l in June 2012. Molecular profiling completed on the patient’s tissue was negative. Pasireotide, a novel multi-somatostatin receptor analogue, was commenced concomitantly with the anti-angiogenesis agent bevacizumab. Results: Treatment response is being assessed with imaging, serial monitoring of serum ACTH levels and skin examination. Interval imaging has shown stable disease, ACTH levels have decreased to 113,000pg/ml. Conclusions: Pituitary carcinomas are extremely rare representing 0.1-0.2% of pituitary neoplasms. To date, there is no established standard treatment, although there are reports of response to temozolamide.Our patient exhibited a clinical improvement and a reduction in ACTH levels after 6 months of combination therapy with pasireotide and bevacizumab. This combination is a possible therapeutic option in patients with metastatic ACTH-producing pituitary carcinoma.