First line treatment of pemphigus vulgaris with a novel protocol in patients with contraindications to systemic corticosteroids and immunosuppressive agents: Preliminary retrospective study with a seven year follow-up

BackgroundConventional therapy for pemphigus vulgaris (PV) consists of high-dose systemic corticosteroids (CS) and immunosuppressive agents (ISA). This combination may be ineffective, cause serious adverse events or relapses in some patients.ObjectiveTo determine if the combination of intravenous immunoglobulin (IVIg) therapy and rituximab (RTX) can be used as first-line therapy in PV patients in whom systemic CS and ISA are contraindicated and evaluate its ability to produce long-term sustained remissions.MethodThis a retrospective study of five male and five female patients (mean age 47.87 years). RTX was administered once weekly for eight consecutive weeks, followed by once monthly for four months (dose 375 mg/m²). Since CD20⁺ B cells were undetectable, IVIg was infused until they reached normal levels (dose 2 g/kg/cycle). IVIg was then continued according to published protocol.ResultsInitial clinical response and complete disease resolution occurred in a mean of 3.2 weeks and 7.4 weeks, respectively. Mean duration of rituximab therapy was 6.09 months and 33.7 months for IVIg therapy. Mean duration of follow-up after the last dose of rituximab was 86.08 months, during which all patients remained in complete remission. Mean length of total follow-up was 103.99 months. No relapses, infections, or hospitalizations were reported.ConclusionsWhen systemic CS and ISA are contraindicated in PV patients, combination RTX and IVIg therapy can produce a prolonged, sustained remission without additional systemic therapy. This positive clinical outcome could be the consequence of pathogenic B cell depletion and restoration of immune regulation.     

Atorvastatin calcium in combination with methylprednisolone for the treatment of multiple sclerosis relapse

This study aimed to investigate the efficacy of combined atorvastatin calcium and methylprednisolone for the treatment of multiple sclerosis relapse. Patients with multiple sclerosis (MS) at the relapse phase were randomized to receive either combined treatment of atorvastatin calcium and methylprednisolone (n = 19) or methylprednisolone alone (n = 19). Expanded Disability Status Scale (EDSS) was administered at baseline, 1 week, 2 weeks, 4 weeks, 3 months, and 6 months after treatment initiation. The number and volume of brain lesions were evaluated using magnetic resonance imaging at baseline and 6 months. The levels of IL-13, IL-35, IFN-γ, and IL-10 in the cerebrospinal fluid were examined using the enzyme-linked immunosorbent assay method. There was no significant difference in EDSS scores at 1, 2, and 4 weeks. At 3 and 6 months, the combined treatment group showed significantly lower EDSS scores than the monotherapy group (P < 0.05). The number and volume of brain lesions in the combined treatment group were significantly lower than the monotherapy group at 6 months (P < 0.001). The mean time to relapse was significantly extended in the combined treatment group than the monotherapy group (P < 0.001). At 2 and 4 weeks, the combined treatment group had significantly higher levels of IL-13, IL-35, and IL-10 in the cerebrospinal fluid than the monotherapy group (P < 0.05), but significantly lower level of IFN-γ (P < 0.001). The levels of IL-13 and IL-10 in the combined treatment group were positively correlated with EDSS scores (r = 0.632, P = 0.001; r = 0.731, P = 0.002). Combined treatment with atorvastatin calcium and methylprednisolone can improve the outcomes of MS relapse compared with glucocorticosteroid alone.     

Efficacy of a targeted cognitive–behavioral treatment program for cannabis use disorders (CANDIS*)

AimsTo examine the efficacy, 3- and 6-month follow-up effects of a psychological treatment for older adolescents and adults with DSM-IV cannabis use disorders. The program was tailored to the needs of this patient population.Experimental proceduresA randomized controlled clinical trial of 122 patients aged 16 to 44 years with DSM-IV cannabis dependence as the main substance use diagnosis was conducted. Patients were randomly assigned to either Active Treatment (AT, n = 90) or a Delayed Treatment Control group (DTC, n = 32). Treatment consisted of 10 sessions of therapy, detailed in a strictly enforced manual. Assessments were conducted at baseline, during each therapy session, at post treatment and at follow-up assessments at 3 and 6 months.ResultsThe treatment retention rate was 88%. Abstinence was achieved in 49% of AT patients and in 13% of those in DTC (p < 0.001; intend-to-treat (ITT) analysis). Further, AT patients improved significantly (p < = 0.001) in the frequency of cannabis use per week, addiction severity, number of disability days, and overall level of psychopathology. Program effects were maintained over a 3-month- (abstinence rate: 51%) and 6-month follow-up (45%) period.ConclusionThe treatment program is effective in obtaining abstinence as well as reducing cannabis use and improves the associated social and mental health burden.     

The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: A systematic review and Meta-analysis

BackgroundThe purpose of this study was to assess the efficacy and safety between tenofovir and entecavir in the treatment of CHB and HBV related cirrhosis through Meta-analysis. MethodsThe electronic databases of PubMed, the Cochrane Library, Nature, CNKI and WanFang data were searched. The key words were: (“tenofovir”, “entecavir”) and (“Chronic Hepatitis B” or “CHB”) and “Liver cirrhosis”. Heterogeneity and report bias were analyzed.ResultsThere was significant difference of ALT norm level in the short-term period of 3 months (RR = 1.43, 95%CI: 1.06–1.94, P < 0.017) and 6 months (RR = 0.89, 95%CI: 0.81–0.97, P < 0.017), and significant difference of undetectable HBV-DNA only in 3 months follow-up period (RR = 1.59, 95%CI: 1.04–2.42, P < 0.017) between TDF and ETV, but no significant difference in the long-term period. There is significant difference between TDF and ETV in eGFR level (RR = 1.601, 95%CI: 1.035–2.478, P = 0.0034) and hypophosphatemia incidence (RR = 4.008, 95%CI: 1.485–10.820, P = 0.006).ConclusionTDF has a better efficacy than ETV in 3 months treatment duration, but intriguingly, TDF might not better than ETV during the 6 months treatment period in the viral suppression and liver function improvement. There's no significant difference between TDF and ETV in the long-term treatment duration and in the treatment of HBV related liver cirrhosis. Both TDF and ETV could influence renal function but patients under TDF therapy may have more risk to suffer from renal damage and hypophosphatemia.     

[Artículo traducido] Impacto de los corticoides sistémicos en el tiempo de hospitalización en pacientes con COVID-19

ObjectiveThe COVID-19 pandemic has posed a threat to hospital capacity due to the high number of admissions, which has led to the development of various strategies to release and create new hospital beds. Due to the importance of systemic corticosteroids in this disease, we assessed their efficacy in reducing the length of stay (LOS) in hospitals and compared the effect of 3 different corticosteroids on this outcome.MéthodWe conducted a real-world, controlled, retrospective cohort study that analysed data from a hospital database that included 3934 hospitalised patients diagnosed with COVID-19 in a tertiary hospital from April to May 2020. Hospitalised patients who received systemic corticosteroids (CG) were compared with a propensity score control group matched by age, sex and severity of disease who did not receive systemic corticosteroids (NCG). The decision to prescribe CG was at the discretion of the primary medical team.ResultsA total of 199 hospitalized patients in the CG were compared with 199 in the NCG. The LOS was shorter for the CG than for the NCG (median = 3 [interquartile range = 0–10] vs. 5 [2–8.5]; p = 0.005, respectively), showing a 43% greater probability of being hospitalised ≤ 4 days than > 4 days when corticosteroids were used. Moreover, this difference was only noticed in those treated with dexamethasone (76.3% hospitalised ≤ 4 days vs. 23.7% hospitalised > 4 days [p < 0.001]). Serum ferritin levels, white blood cells and platelet counts were higher in the CG. No differences in mortality or intensive care unit admission were observed.ConclusionsTreatment with systemic corticosteroids is associated with reduced LOS in hospitalised patients diagnosed with COVID-19. This association is significant in those treated with dexamethasone, but no for methylprednisolone and prednisone.     

Short term omega-3 polyunsaturated fatty acid supplementation induces favorable changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; A randomized clinical trial

IntroductionOmega-3 polyunsaturated fatty acids (omega 3-PUFAs) seem to favorably affect cardiac hemodynamics and may benefit the clinical course of heart failure patients. The role of omega 3-PUFAs supplementation on the left and right ventricular function of patients with chronic compensated systolic heart failure, under optimal treatment, was studied.Methods205 consecutive patients with chronic compensated heart failure, due to ischemic (IHF) or dilated cardiomyopathy (DCM)-NYHA classification I–III, under optimal medical treatment, were enrolled. Participants were 1-to-1 randomized on 1000 mg omega 3-PUFA supplementation or no supplementation, in a non-blinded fashion. Echocardiographic assessment was performed at first visit and 6 months after. Plasma BNP and serum creatinine levels were also measured.ResultsAs compared with the control group, BNP levels in omega 3-PUFA intervention group were 34.6% lower (p = 0.001); end-diastolic and end-systolic left ventricle dimensions were decreased by 2.5% (p = 0.047) and 3.7% (p = 0.01), maximum diameter of left atrium was decreased by 8.4% (p = 0.004), left atrium ejection fraction was ameliorated by 6.03% (p = 0.021) and as regards tissue Doppler parameters, TDI_Etv/Atv was decreased in omega 3-PUFA intervention group by 6.3% (p = 0.038). Moreover, improvement in diastolic indices was more prominent in subjects with DCM as compared to IHF patients.ConclusionOmega 3-PUFA supplementation was associated with improved left diastolic function and decreased BNP levels in patients with chronic heart failure. These findings suggest a beneficial role of omega 3-PUFAs on the hemodynamic course of patients with systolic heart failure.     

The effectiveness of outreach case management in re-enrolling discharged methadone patients

BackgroundHeroin dependence is a chronic relapsing disease often requiring multiple treatment experiences. Despite this knowledge, few methadone programs follow-up with discharged patients who frequently continue to engage in risky behaviors. The aim of this project was to evaluate the effectiveness of outreach case management for post-discharged methadone patients.MethodsAt 90 days post-discharge 128 active out of treatment heroin users were randomly assigned to receive either a passive referral (PR) for drug treatment (n = 52) or were provided with 6 weeks of outreach case management (OCM), an intervention designed to help motivate and coach patients to re-enter treatment (n = 76).ResultsAt 6 months post-baseline 29% of the OCM participants had successfully re-enrolled in drug treatment compared to 8% of the PR participants (χ² = 7.6, d.f. = 1, p = 0.006). A logistic regression analysis showed that OCM participants were nearly six times more likely than PR participants to re-engage in MMT (OR = 5.8, CI = 1.6–20.8, p = 0.008). Moreover, OCM subjects had fewer opiate and cocaine positive urines at the 6-month follow-up compared to PR subjects.ConclusionsThe findings highlight the importance of engaging former patients in treatment and actively assisting in treatment re-entry. OCM is a simple approach to reduce the number of out-of-treatment drug users, although availability of treatment funding limits enrollment opportunities.     

Effect of HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase inhibitors on the concentration of insulin-like growth factor-1 (IGF-1) in hypercholesterolemic patients

Studies have shown that HMG-CoA reductase inhibitors (statins) play an important role in the prevention and treatment of atherosclerosis and hyperlipidemia. The aim of this study was to investigate the effect of 3-month treatment with simvastatin on serum levels of Insulin-Like Growth Factor-1 (IGF-1) in patients with diagnosed hypercholesterolemia. In total, 156 patients with hypercholesterolemia were recruited for the study. The inclusion criteria for this study were designed to allow the enrollment of a representative group of patients for cytokine studies. The patients were divided into two groups: (1) patients with a mild-tomoderate risk of heart disease, who had total cholesterol (TC)  <  300 mg/dl (7.8 mmol/l), LDL-cholesterol > 210 mg/dl (5.4 mmol/l), and who lacked risk factors for coronary artery disease (CAD) after treatment with a diet for 3 months; (2) patients with a high-to very high risk of CAD, who had TC > 300 mg/dl (7.8 mmol/l), LDL-cholesterol > 210 mg/dl (5.4 mmol/l), and at least two risk factors for CAD after treatment with a diet and administration of simvastatin (20 mg/day) for a three month period. The control group consisted often healthy volunteers who each had a normal lipid profile. Total cholesterol, LDL-cholesterol and IGF-1 concentrations were measured at baseline and either after six months of dietary supplementation (first group) or after three months of dietary supplementation and three months of simvastatin treatment (second group). Conclusions: In patients with mild-tomoderate risk of CAD, a decreased serum concentration of IGF-1 was observed three months after beginning a low-fat diet. However, no changes in the serum concentration of IGF-1 were noted in patients with high-to-very high risk of CAD. Additional three-month treatment with simvastatin decreased the serum concentration of IGF-1.     

Morphological changes and viability of primary cultured human ocular trabecular meshwork cells after exposure to air

PurposeTo investigate the possible toxic effect of air exposure for an in vitro model of primary human ocular trabecular meshwork cells (HTM).MethodsHTM were isolated from five donor eyes and cultivated at 37 °C. After reaching confluence the cells were seeded on two well chamber slides. The chamber slides were turned upside down in a Petri culture dish full of culture medium and filled with air using a 5 ml syringe, starting this way the exposure of the cells to the air. Subsequently they were placed in the incubation chamber at 37 °C. Six groups of HTM cultures were set up: group 1 consisted of samples in which HTM were exposed to air for 30 min, group 2 for 1 h, group 3 for 3 h, group 4 for 6 h, group 5 for 12 h and group 6 for 24 h.ResultsAt 3 h after exposure, the morphology of the cells was still intact, at 6 h few cells appeared deformed and exhibited characteristics of more senescent cells. At 12 h after exposure to air the HTM cells started losing their typical morphology and appeared enlarged and compromised. Viability was superior to 94% in groups 1–3 while for groups 4, 5, 6 it was 82.7%, 39.5% and 12.7% respectively.ConclusionThe toxic effect of air exposure for the studied in vitro model of HTM is not significant for the time period of one to three hours. However it starts reducing viability and alternating morphology 6 h after exposure until the time period of 24 h, where the percentage of living cells is drastically decreased. Therefore, we suggest that the use of an air bubble especially in glaucomatous patients should be applied with caution.     

Progesterone therapy in women with epilepsy

BackgroundProgesterone with its anti-seizure effect plays a role in the pathophysiology of catamenial epilepsy which affects 31–60% of epileptic women. In this study, an attempt to treat women suffering from catamenial epilepsy with progesterone, as an adjuvant drug, was made.MethodsThe treatment was given to 36 women aged 20–40 years (mean age: 30.75 ± 6.05) with seizures in the entire second half of the menstrual cycle, who were found to have low serum levels of progesterone on days 22, 27, 28 of the cycle in comparison with a control group of healthy women. The patients were administered progesterone in a daily dose of 50 mg on days 16–25 of each cycle. The serum levels of antiepileptic drugs were assayed. The period of progesterone therapy ranged from 3 to 45 months (17.7 on average).ResultsThree patients were free of secondary generalized seizures, and one – of simple partial seizures. Adecline in the frequency of primary and secondary generalized seizures by 20–96% (55.9% on average) was accomplished in 18 patients (primary generalized by 20–96% – 54.7% on average, and secondarily generalized by 38–85% – 59% on average).Adecline in the frequency of complex partial seizures by 38–87% (63.1% on average) was achieved in 15 women. In 1 patient, the frequency of myoclonic seizures decreased by 46%. There was no improvement in 5 women (3 patients with generalized, 1 with complex partial and 1 with simple partial seizures). An exacerbation of seizure frequency occurred in 5 patients. Adverse effects were not found in any of the subjects. The average concentrations of antiepileptic drugs during hormonal therapy were in the therapeutic range.ConclusionProgesterone combined with antiepileptic therapy was well tolerated and resulted in a significant reduction of seizure frequency in majority of patients with catamenial epilepsy.     

The effects of corticosteroids on cytokine production from asthma lung lymphocytes

BackgroundLymphocytes play a central role in the pathophysiology of asthma. Corticosteroids have a limited effect in severe asthma and we hypothesise that lymphocytes play a central role in corticosteroid insensitivity. We investigated the effects of corticosteroids on cytokine production from lung lymphocytes obtained from patients with moderate severe asthma (MSA) compared to mild asthma (MA) and healthy non-smokers (HNS).MethodsBronchoalveolar lavage (BAL) cells obtained by bronchoscopy from patients with MSA and MA (n = 11 and n = 14 respectively) and HNS (n = 7) were stimulated with CD2/3/28 beads to activate the lymphocytes, in the presence or absence of dexamethasone (0.01–1 μM). Supernatants were assayed for IL-2, IFNγ, IL-17, IL-13 and IL-10 production.ResultsDexamethasone caused variable inhibition of cytokines; 1 μM inhibited IL-10 and IL-17 by 50% or lower, while inhibition > 50% was observed for IL-2, IL-13 and IFNγ. The effect of dexamethasone on IL-13 production was reduced in MSA.ConclusionThese findings suggest that the production of specific lymphocyte derived cytokines is poorly suppressed by corticosteroids in MSA, which may be responsible for persistent airway inflammation in these patients     

The association of race, comorbid anxiety, and antidepressant adherence among Medicaid enrollees with major depressive disorder

BackgroundDepressed patients often have comorbid anxiety. African-Americans with depression are less likely to adhere to antidepressant treatment. Knowledge of the association between race, comorbid anxiety, and adherence among Medicaid enrollees with depression is limited.ObjectiveThe objective of this study was to evaluate the association of race, comorbid anxiety, and antidepressant adherence, and persistence among Medicaid enrollees with major depressive disorder (MDD).MethodsThe MarketScan^® Multi-State Medicaid Database (Thomson Reuters, Ann Arbor, MI) was used in this retrospective cross-sectional study. Medicaid enrollees aged between 18 and 64 years, with MDD but without bipolar disorders, and with a newly initiated antidepressant between January 1, 2004 and December 31, 2006 were identified. An index date was assigned corresponding to the newly initiated antidepressant. Patients having claims for any antidepressant refills during the 12 months before the index date were excluded. Eligible patients were then followed-up for 12 months after the index date. Adherence was measured by a modified medication possession ratio. Adherence was evaluated using multivariate logistic regression. Persistence was assessed based on treatment discontinuation and examined by Kaplan-Meier survival curves and Cox-propositional hazard regression models.ResultsA total of 3083 Medicaid patients with MDD were included. Approximately, 25% of patients had comorbid anxiety. The odds of adhering to antidepressants were 40% lower among African-Americans than Caucasians, adjusting for covariates (AOR [adjust odds ratio] = 0.60; 95% confidence interval [CI] = 0.51-0.72, P < .001). MDD patients with comorbid anxiety were more likely to adhere to antidepressants than patients with MDD alone (AOR = 1.55, 95% CI = 1.27-1.90, P < .001). African-Americans had a higher hazard of not persistently taking antidepressants (hazard ratio = 1.47, 95% CI = 1.30-1.65, P < .001). The interaction between race and comorbid anxiety was not associated with adherence or persistence.ConclusionsAmong Medicaid enrollees with MDD, race and comorbid anxiety disorders are significantly associated with antidepressant adherence and persistence. Physicians need to recognize comorbid anxiety and race as 2 important determinants of antidepressant use behaviors when they encounter Medicaid patients with MDD.     

Análisis de minimización de costes de darbepoetina alfa frente a epoetina alfa en pacientes con insuficiencia renal crónica sometidos a hemodiálisis

IntroductionMultiple studies have shown that epoetin alpha (r-HuEpo) and darbepoetin alpha (NESP) are similarly effective and safe for maintaining haemoglobin levels in patients with chronic kidney disease (CKD). Nevertheless, there is some debate over their cost-effectiveness. The purpose of this study is to carry out a cost-minimisation analysis including a comparison of the costs to the hospital arising from treatment with r-HuEpo vs. NESP.MethodsProspective observational study. We included CRF patients on haemodialysis with no iron, vitamin B12 or folate deficiencies, treated with stable doses of IV r-HuEpo. Follow-up was performed over three periods: the first during six months, maintaining prior treatment with r-HuEpo; the second for eight months, after changing to NESP, and the third, during the final eight months, following resuming r-HuEpo treatment. For converting both treatments, the conversion factor established on technical sheet 1:200 was used.Results51 patients completed the study and were valid for analysis. Their mean age was 68.3 years, and 18 were women (35.3%). The mean weekly doses at the end of each period were 8,058.8 (SD 3,911.1) IU for the EPO1 period, 39.4 (SD 21.6) μg for NESP and 7,882.4 (SD 4,594.1) IU for EPO2. The weekly costs for each treatment showed significant differences between NESP and r-HuEpo: the cost of NESP was higher.ConclusionIn our study, we found that r-HuEpo and NESP were similarly effective in patients with CRF on haemodialysis, but that there was a significant cost increase associated with NESP treatment.     

Immunomodulatory effect of pleuran (β-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections

ObjectivesRecurrent respiratory tract infections (RRTIs) represent a very important problem in daily clinical practice because of their significant contribution to morbidity in children. Several natural nutritional supplements have been used in the prevention of RRTIs, but the clinical efficacy of only a few preparations is supported by scientific evidence.Materials and methodsIn a double-blind, placebo-controlled, randomised, multicentre study, we have observed a group of 175 children (aged 5.65 ± 2.39 years) with more than 5 respiratory infections that occurred during the 12 months prior to the beginning of the study. Children were randomised into an active group, treated with Imunoglukan P4H® syrup (with pleuran-β-glucan from Pleurotus ostreatus and vitamin C), or a placebo group (vitamin C only). During the 3 visits, within a 12-month period, questionnaires were completed, and blood samples were examined for immune parameters.ResultsIn the active group, 36% of the children did not suffer from any respiratory infections throughout the treatment, compared to 21% in the placebo group (p < 0.05). Imunoglukan P4H® also significantly decreased the frequency of flu and flu-like disease and the number of lower respiratory tract infections. Imunoglukan P4H® treatment resulted in a statistically significant modulation of humoral and cellular immunity.ConclusionsResults from this study demonstrate that Imunoglukan P4H® is effective in the prevention of RRTIs in children. Furthermore, our results also revealed complex immunomodulatory activity of this product. This is the first double-blind, placebo-controlled study in children with RRTIs that has addressed the preventive effects of pleuran on morbidity caused by respiratory infections.     

Long-term effectiveness and safety of natalizumab in a Portuguese population

ObjectivesNatalizumab long-term effectiveness data in real-world relapsing­remitting multiple sclerosis (RRMS) is needed. Our objective is to report the long­term effectiveness and safety of natalizumab in a cohort of RRMS patients.MethodsThis is a retrospective study of natalizumab treatment for two years or longer in RRMS. Annualized relapse rate, Expanded Disability Status Scale (EDSS), brain magnetic resonance imaging T2 lesion volume, JC virus antibody status, previous treatments and adverse events were analysed.ResultsSeventy-one patients were included with a mean treatment duration of 44.86 ± 17.39 months. Over the treatment duration there was a significant decrease in annualized relapse rate (88.37%) and EDSS (28.57%); no evidence of clinical disease activity in 73.24% and 61.97% after one and two-years respectively; and brain magnetic resonance imaging T2 lesion volume remained stable. Forty patients suspended natalizumab, in 85% due to high risk of developing progressive multifocal leukoencephalopathy (PML). The major complication was PML (n = 3).ConclusionsNatalizumab showed effectiveness in the long-term follow up period of our cohort, with reduction of ARR, EDSS, and MRI lesion load stabilization. PML was the major complication.     

Influence of the number and interval of treatment cycles on cytokine-induced killer cells and their adjuvant therapeutic effects in advanced non-small-cell lung cancer (NSCLC)

ObjectiveCytokine-induced killer (CIK) cells have important therapeutic effects in adoptive cell transfer (ACT) for the treatment of various malignancies. In this study, we focused on in vitro expansion of CIK cells and their clinical efficacy in combination with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).MethodsA total of 64 patients with NSCLC (enrolled from 2011 to 2012), including 32 patients who received chemotherapy alone or with sequential radiotherapy (conventional treatment, control group) and 32 patients who received conventional treatment and sequential CIK infusion (study group), were retrospectively analyzed. The time to progression (TTP), overall survival (OS) and adverse effects were analyzed and the phenotype of lymphocytes in CIK population was also determined by flow cytometry.ResultsAfter in vitro expansion, the average percentage of CIK cells was 26.35%. During the 54-month follow up, the median OS and TTP were significantly longer in the study group than in the control group (P = 0.0189 and P = 0.0129, respectively). The median OS of the ACT ≥ 4 cycles subgroup was significantly longer than that of the ACT < 4 cycles subgroup (P = 0.0316). The percentage of CIK cells in patients who received ≥ 4 cycles of ACT was higher than that in patients treated with < 4 cycles of ACT (P = 0.0376). Notably, CIK cells were difficult to expand in vitro in some patients after the first ACT cycle but became much easier as the treatment cycles increased monthly. Longer treatment interval negatively impacted the expansion of CIK cells.ConclusionsSystematic immune levels can be increasingly boosted by reinfusion of ACT. Conventional treatment plus CIK cells is an effective therapeutic strategy to prevent progression and prolong survival of patients with advanced NSCLC.     

Association between corneal temperature and mental status of treatment-resistant schizophrenia inpatients

IntroductionPreliminary point-prevalent data suggest that drug-free schizophrenia patients may exhibit increased body/corneal temperature, that antipsychotic drugs (APDs) may decrease body/core temperature and that patients' mental status might be associated with their body/corneal temperature. Hence, we hypothesized that treatment-resistant psychotic APD-treated schizophrenia patients' mental status may correlate with their corneal temperature during a continuous 6-week period.MethodsCorneal temperature of 12 treatment-resistant schizophrenia inpatients and 16 healthy volunteers was evaluated 2–3 times a week during 6 consecutive weeks using a flir thermal imaging camera.ResultsA significant and substantial correlation was found between inpatients' mean weekly Positive and Negative Syndrome Scale (PANSS)'s total scores and their mean weekly corneal temperature during the 6-week study period (r = 0.82; n = 6 weeks; p = 0.043). There was no significant difference in mean 6-week corneal temperature between the patient group and the healthy subjects (34.25 ± 0.64 °C vs. 34.39 ± 0.69 °C, respectively; t = 1.127, df = 131, p = 0.26).ConclusionsThis study indicates that treatment-resistant overtly psychotic schizophrenia inpatients' mental status (as assessed by the PANSS) correlates with their corneal temperature. The relevance of these phenomena to the pathophysiology of schizophrenia, the biological mechanism underlying corneal temperature alterations and the possible role of temperature-modulating drugs (neuroleptics or non-neuroleptics) on schizophrenic psychosis merits further large-scale investigation in both medicated- and drug-free schizophrenia patients compared to matched controls.     

A double-blind, placebo-controlled study of sertraline with naltrexone for alcohol dependence

IntroductionSignificant preclinical evidence exists for a synergistic interaction between the opioid and the serotonin systems in determining alcohol consumption. Naltrexone, an opiate receptor antagonist, is approved for the treatment of alcohol dependence. This double-blind placebo-controlled study examined whether the efficacy of naltrexone would be augmented by concurrent treatment with sertraline, a selective serotonin receptor uptake inhibitor (SSRI).MethodsOne hundred and thirteen participants meeting DSM IV alcohol dependence criteria, who were abstinent from alcohol between 5 and 30 days, were randomly assigned to receive one of two treatments at two sites. One group received naltrexone 12.5 mg once daily for 3 days, 25 mg once daily for 4 days, and 50 mg once daily for the next 11 weeks, together with placebo sertraline. The other group received naltrexone as outlined and simultaneously received sertraline 50 mg once daily for 2 weeks, followed by 100 mg once daily for 10 weeks. Both groups received group relapse prevention psychotherapy on a weekly basis.ResultsCompliance and attendance rates were comparable and high. The groups did not differ on the two primary outcomes, time to first drink and time to relapse to heavy drinking, or on secondary treatment outcomes. With the exception of sexual side effects which were more common in the combination group, most adverse events were similar for the two conditions.ConclusionsAs the doses are tested in combination with specialized behavioral therapy, this study does not provide sufficient evidence for the combined use of sertraline and naltrexone above naltrexone alone.     

Efectividad y seguridad de la terapia de rescate en pacientes VIH

IntroductionThe treatment used after failure of at least two lines of antiretroviral treatment in HIV patients is called salvage therapy. The study aims to describe the characteristics of HIV patients subjected to such a regimen, and determine the safety and effectiveness of treatment with tipranavir (TPV), darunavir (DRV), enfuvirtide (ENF) and etravirine (ETR) combined with an optimised antiretroviral regimen.Patients and methodsHIV patients treated with ENF, TPV, DRV or ETR in a tertiary hospital infectious diseases department subjected to at least 12 weeks treatment. The patient characteristics are described and the effectiveness, durability and adherence to the treatment analysed.ResultsThere were 28 patients studied, with an average of 10 treatment regimens prior to starting salvage therapy (SD = 3.5; 95 % CI, 8.9-11.1). A total of 85.7 % patients had treatment adherence > 90 %. For ENF, 70.8 % of the treatment lines were suspended during follow-up. After salvage therapy, the percentage of patients with viral load (VL) < 400 copies/ml doubled, and cases with undetectable CV (< 50 copies/ml) almost tripled. The treatments used did not change the liver or kidney profiles; however, they changed the lipid profile and increased the percentage of patients with hyperglycaemia.ConclusionsThe salvage therapy studied was effective. Good adherence to the therapy is critical for its effectiveness.     

Concentration of Il-1β, Il-2, Il-6, TNFα in the blood serum in children with generalized epilepsy treated by valproate

BackgroundThe aim of the study was the comparison of concentrations of IL-1β, IL-2, IL-6 and TNFα before and after valproate (VPA) treatment in blood serum in patients with generalized seizures diagnosed and treated in the Department of Developmental Neurology, Poznan University of Medical Sciences from January 2006 to May 2007.MethodsThe analysis was conducted in a group of 21 patients with well controlled, generalized seizures (mean age 7.7 ± 4.7 years) before and after 4–6 months of VPA therapy. Quantitative determination IL-1β, IL-2, IL-6 and TNFα were performed with method of enzyme-linked immunosorbent assay (ELISA). The serum drug concentration was determined with the use of fluorescence-polarization-immunoassay system (FPIA).ResultsThe concentration of IL-6 in blood serum of patients decreased significantly (p < 0.001) after 4–6 months of VPA therapy, but concentration of IL-1β (p = 0.732), IL-2 (p = 0.865), TNFα (p = 0.079) did not change significantly. The serum concentration of VPA in all of patients was in therapeutic range (mean 77.53 ± 19.71 μg/ml).ConclusionsThe serum level of pro-inflammatory IL-6 in patients with generalized epilepsy decreased in statistically significant way during VPA therapy, so the anti-inflammatory properties of VPA are also important for the effective control of seizure. Due to the incompatibility of reports on the influence of VPA on cytokine system in patients with generalized epilepsy, this problem needs more investigations, especially in the group of children.