Efficacy analysis of hydroxychloroquine therapy in systemic lupus erythematosus: a study on disease activity and immunological biomarkers

Background

Hydroxychloroquine (HCQ) is a widely prescribed medication to patients with systemic lupus erythematosus (SLE), with potential anti-inflammatory effects. This study was performed to investigate the efficacy of HCQ therapy by serial assessment of disease activity and serum levels of proinflammatory cytokines in SLE patients.

Methods

In this prospective cohort study, 41 newly diagnosed SLE patients receiving 400 mg HCQ per day were included. Patients requiring statins and immunosuppressive drugs except prednisolone at doses lower than 10 mg/day were excluded. Outcome measures were assessed before commencement of HCQ therapy (baseline visit) as well as in two follow-up visits (1 and 2 months after beginning the HCQ therapy). Serum samples of 41 age-matched healthy donors were used as controls.

Results

Median levels of IL-1β (p?<?0.001), IL-6 (p?=?0.001), and TNF-α (p?<?0.001) were significantly higher, whereas, median CH50 level was significantly lower (p?<?0.001) in SLE patients compared with controls. Two-month treatment with HCQ resulted in significant decrease in SLEDAI-2K (p?<?0.001), anti-dsDNA (p?<?0.001), IL-1β (p?=?0.003), IL-6 (p?<?0.001) and TNF-α (p?<?0.001) and a significant increase in CH50 levels (p?=?0.012). The reductions in SLEDAI-2K and serum levels of IL-1β and TNF-α were significantly greater in the first month compared with the reductions in the second month.

Conclusion

HCQ therapy is effective on clinical improvement of SLE patients through interfering with inflammatory signaling pathways, reducing anti-DNA autoantibodies and normalizing the complement activity.

     

Normal-appearing brain t1 relaxation time predicts disability in early primary progressive multiple sclerosis

OBJECTIVE: To investigate whether patients with early primary progressive multiple sclerosis show changes in T1 relaxation time (T1-RT) in normal-appearing white matter (NAWM) and normal-appearing gray matter (NAGM) during 2 years and whether T1-RT at baseline predicts disability. METHODS: Twenty-one patients and 12 control subjects were studied at baseline and after 2 years. Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores were assessed. T1 relaxation time histograms of NAWM and NAGM were obtained in all subjects, and mean, peak height, and peak location of the histograms were measured. Paired t tests were used to compare baseline and 2-year histogram values in patients and control subjects. To investigate whether T1-RT predicted clinical changes, multiple linear regression analysis was used. RESULTS: Patients showed increases in NAWM and NAGM T1-RT mean and peak location during follow-up, and significant decreases in NAWM and NAGM peak height. Baseline NAWM T1-RT mean values and peak height predicted disability at 2 years, as measured with the Multiple Sclerosis Functional Composite score. CONCLUSION: T1 relaxometry is a good marker of disease progression and has prognostic potential in primary progressive multiple sclerosis.     

The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus

Objective

The antimalarial medication hydroxychloroquine has been proposed as a thromboprotective agent in systemic lupus erythematosus (SLE), but studies thus far have been limited by the possibility of confounding by indication. This study was conducted to assess whether exposure to antimalarial drugs is associated with a decrease in thrombovascular events (TEs) in patients with SLE.

Methods

The study was designed as a nested case–control study embedded in an inception cohort of patients with SLE, which allowed adjustments for possible confounding by calendar year, duration of disease, duration of observation, and severity of lupus. After controlling for the possible confounding variables in conditional logistic regression models, the use of antimalarial drugs was assessed for its effects on the development of TEs in lupus patients.

Results

Fifty‐four cases of TE were identified, and these were matched with 108 control subjects (lupus patients without TEs). Univariate analyses identified older age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01–1.07) or being older than age 50 years (OR 3.5, 95% CI 1.4–8.6) and ever having hypertension (OR 2.5, 95% CI 1.0–5.8) as being associated with an increased risk of TEs, whereas use of antimalarial drugs (OR 0.31, 95% CI 0.13–0.71) was associated with a decreased risk of TEs. Separate analyses were done for arterial and venous TEs, which yielded similar results. In multivariate analyses, use of antimalarial drugs (OR 0.32, 95% CI 0.14–0.74) and older age (OR 1.04, 95% CI 1.01–1.07) were the only 2 variables that remained significant.

Conclusion

The results from this nested case–control study demonstrate that, after accounting for the effects of disease severity, disease duration, and calendar year, antimalarial drugs were found to be thromboprotective, being associated with a 68% reduction in the risk of all TEs, with a range of risk reduction of at least 26% up to as high as 86%.

     

Diagnostic histological features of metastatic lymph nodes in adenosquamous carcinoma

Laryngeal adenosquamous carcinoma (ASC) is a rare malignancy, and the problems in true diagnosis of this entity are well known. In this paper, we describe a case of ASC and discuss its distinct histopathology in metastatic lymph nodes. A heavy smoker man presented with a progressive neck mass. Based on incisional biopsy, diagnosis of squamous cell carcinoma (SCC) was made and total laryngectomy with bilateral radical neck dissection was performed. Sections of primary tumor showed a well-differentiated SCC. However, lymph node metastases had a distinct feature of glandular structures. Further investigation with Mayer's mucicarmine stain confirmed the presence of rare scattered glands in primary tumor and the final diagnosis was changed to ASC. Adenosquamous carcinoma is a distinct entity and must be distinguished from the common SCC of larynx. As a result, when a lesion with diagnosis of squamous cell carcinoma shows evidence of glandular differentiation in a subsequent biopsy or in nodal metastases, more investigation is necessary. Moreover, the glandular structures in primary tumor, as in this case, may be rare and inconspicuous. Therefore, we suggest the precise evaluation of metastatic lymph nodes for any laryngeal tumor with diagnosis of SCC. This helps to make appropriate therapeutic decisions with respect to the aggressive behavior of ASC and its high propensity for lymph node metastasis.     

Implementing root cause analysis in Iranian hospitals: challenges and benefits

Root cause analysis (RCA) has been widely used for retrospective investigations of patient safety incidents. To increase patient safety competencies, RCA has recently been introduced in Iranian hospitals. The aims of the current study were to explore team members' experiences and perceptions of RCA and to identify the challenges and benefits of using it in Iranian hospitals from their perspective. A qualitative study was conducted consisting of 32 semi‐structured interviews with health professionals who participated in the national training programme and were involved in RCA investigations. Data were analysed using the thematic analysis method. The participants encountered a range of obstacles while conducting RCA, including time constraints, a lack of resources, the blame culture and unsupportive colleagues. They stressed the need for further leadership support and cultural change within the Iranian healthcare system to facilitate the application of RCA. RCA was perceived as a beneficial analytical tool that improved patient care, fostered teamwork and communication among staff and promoted safety culture. This study concluded that applying RCA in the Iranian healthcare setting has had a significant impact on improving commitment to safety. However, the general adoption of this method is hindered by the lack of workplace and system supports. To maximize profits from RCA, clinical leaders must assign a high priority to RCA investigations and support RCA team efforts. Copyright © 2016 John Wiley & Sons, Ltd.     

The effect of fresh frozen plasma in severe closed head injury

OBJECTIVE: Traumatic brain injury (TBI) is one of the most common causes of morbidity and mortality. Coagulopathy, commonly occurring after severe TBI, is associated with poor outcome and secondary complications, especially delayed traumatic intracerebral hematoma (DTICH). In this study we evaluated the effect of fresh frozen plasma (FFP) on the reduction in the incidence of DTICH in severe closed head injury victims. METHODS: This study was carried out as a double-blind randomized clinical trial. Ninety patients were entered in two parallel groups taking either FFP or normal saline (N/S). Patients' selection criteria for both groups were: severe closed head injury (Glasgow coma scale < or =8), no mass lesion required evacuation and no history of coagulopathy. The clinical findings, laboratory data, computed tomography (CT) scans and Glasgow outcome scale after 1 month were assessed and compared in two groups. RESULTS: Out of 90 patients, 44 received FFP and 46 received N/S. The development of new intracerebral hematoma in follow-up CT scans were more common in the FFP group than the N/S group (p=0.012). Both groups showed similar frequency of poor outcome (p=0.343). The mortality was significantly more common in the FFP group than in the N/S group (63% versus 35%, p=0.006). CONCLUSION: The result of this study revealed that early empirical infusion of FFP in patients with severe head injury may lead to adverse effects, such as an increase in the frequency of DTICH and an increase in the mortality.     

Evaluation of the effects of pulsed wave LLLT on tibial diaphysis in two rat models of experimental osteoporosis,as examined by stereological and real-time PCR gene expression analyses

Osteoporosis (OP) and osteoporotic fracture are major public health issues for society; the burden for the affected individual is also high. Previous studies have shown that pulsed wave low-level laser therapy (PW LLLT) has osteogenic effects. This study intended to evaluate the impacts of PW LLLT on the cortical bone of osteoporotic rats’ tibias in two experimental models, ovariectomized and dexamethasone-treated. We divided the rats into four ovariectomized induced OP (OVX-d) and four dexamethasone-treated (glucocorticoid-induced OP, GIOP) groups. A healthy (H) group of rats was considered for baseline evaluations. At 14 weeks following ovariectomy, we subdivided the OVX-d rats into the following groups: (i) control which had OP, (ii) OVX-d rats treated with alendronate (1 mg/kg), (iii) OVX-d rats treated with LLLT, and (iv) OVX-d rats treated with alendronate and PW LLLT. The remaining rats received dexamethasone over a 5-week period and were also subdivided into four groups: (i) control rats treated with intramuscular (i.m.) injections of distilled water (vehicle), (ii) rats treated with subcutaneous alendronate injections (1 mg/kg), (iii) laser-treated rats, and (iv) rats simultaneously treated with laser and alendronate. The rats received alendronate for 30 days and underwent PW LLLT (890 nm, 80 Hz, 0.972 J/cm²) three times per week during 8 weeks. Then, the right tibias were extracted and underwent a stereological analysis of histological parameters and real-time polymerase chain reaction (RT-PCR). A significant increase in cortical bone volume (mm³) existed in all study groups compared to the healthy rats. There were significant decreases in trabecular bone volume (mm³) in all study groups compared to the group of healthy rats. The control rats with OP and rats from the vehicle group showed significantly increased osteoclast numbers compared to most other groups. Alendronate significantly decreased osteoclast numbers in osteoporotic rats. Concurrent treatments (compounded by PW LLLT and alendronate) produce the same effect on osteoporotic bone.     

Comprehensive review of hyperbaric oxygen therapy

ABSTRACT: Hyperbaric oxygen therapy involves inspiration of pure high pressure oxygen. For the past 20 years, administration of 100% high pressure oxygen and its potential benefits in management of diseases have been more clarified. Physiological advantages advocate HBO for the first-line treatment of several conditions. The specialty of craniofacial surgery is broad and deals with a diverse range of complications. The goal of this review is to help surgeons in their treatment planning by categorizing the indications of HBO therapy for oral and maxillofacial surgery. We also assess research data substantiating these indications where we believe basic physiological mechanisms and clinical evidences support further investigation on HBO efficacy to greater understanding of its potential benefit in oral and maxillofacial surgery.     

Myricetin Selectively Induces Apoptosis on Cancerous Hepatocytes by Directly Targeting Their Mitochondria

Hepatocellular carcinoma (HCC) is the third most common cause of cancer‐related death. In patients for whom HCC could not be detected early, current treatments show poor tolerance and low efficacy. So, alternative therapies with good efficacy are urgently needed. The aim of this research was to evaluate the selective apoptotic effects of myricetin (MYR), a flavonoid compound, on hepatocytes and mitochondria obtained from the liver of HCC rats. In this study, HCC induced by diethylnitrosamine (DEN), as an initiator, and 2‐acetylaminofluorene (2‐AAF), as a promoter. To confirm the HCC induction, serum levels of alpha‐fetoprotein (AFP), AST, AST and ALP and histopathological changes in the liver tissue were evaluated. Rat liver hepatocytes and mitochondria for evaluation of the selective cytotoxic effects of MYR were isolated, and mitochondrial and cellular parameters related to apoptosis signalling were then determined. Our results showed that MYR was able to induce cytotoxicity only in hepatocytes from the HCC but not from the untreated control group. Besides, MYR (12.5, 25 and 50 μM) induced a considerable increase in reactive oxygen species (ROS) level, mitochondrial swelling, mitochondrial membrane permeabilization (MMP) and cytochrome c release only in cancerous but not in untreated normal hepatocyte mitochondria. MYR selectively increased caspase‐3 activation and apoptotic phenotypes in HCC, but not untreated normal hepatocytes. Finally, our finding underlines MYR as a promising therapeutic candidate against HCC and recommends the compound for further studies.     

Serum triiodothyronine level as an indicator of inflammation in patients undergoing dialysis

INTRODUCTION. It has been shown that inflammation affects thyroid function. In patients with end-stage renal disease, low plasma triiodothyronine (T3) may be an unsuspected expression of the inflammatory state of these patients. This study evaluated the correlation between T3 and high-sensitivity C-reactive protein (HSCRP) levels in patients on peritoneal dialysis (PD) and hemodialysis. MATERIALS AND METHODS. This is a cross-sectional study aiming at the correlation between T3 and HSCRP levels among 30 patients on PD, 30 patients on hemodialysis, and 20 healthy individuals. Serum levels of HSCRP, T3, thyroxine (T4), thyroid stimulating hormone, T3 resin uptake, and free T3 index (FT3I) and free T4 index (FT4I) were compared between the three groups. RESULTS. There were no significant differences between hemodialysis and PD patients in respect to T3, T4, FT3I, and FT4I. In PD and hemodialysis patients, T3 and FT3I were lower than in controls (P < .001), but there was no significant difference between PD and hemodialysis patients. T3 resin uptake and thyroid stimulating hormone differed significantly between PD and hemodialysis patients. There was a significant inverse correlation between HSCRP and T3 and FT3I among hemodialysis patients (P = .04); however, there was no such correlations in PD patients. CONCLUSIONS. The relationship between T3 and HSCRP suggests that inflammation might be involved in the low T3 syndrome in hemodialysis patients, but we did not find a significant correlation between T3 and HSCRP levels in patients on peritoneal dialysis.