CsA Patients Research Articles

Curative effect analysis of anterior cervical discectomy and fusion in patients with cervical spondylosis of vertebral artery type

To investigate the clinical effect of anterior cervical discectomy and fusion (ACDF) in the treatment of cervical spondylosis of vertebral artery type(CSA). The clinical data of 42 patients with CSA from January 2020 to January 2022 were retrospectively analyzed. There were 25 males and 17 females, aged from 30 to 74 years old with an average of (53.9±11.0) years old. There were 18 cases with single-segment lesions, 17 cases with two-segment lesions, and 7 cases with three-segment lesions. The American Academy of Otolaryngology-Head and Neck Surgery's Hearing and Balance Committee score (CHE), the Neck Disability Index (NDI) and the cervical curvature Cobb angle were recorded before surgery and after surgery at 6 months. All 42 ACDF patients were followed up for 6 to 30 months with an average of (14.0±5.2) months. The operative time ranged from 95 to 220 min with an average of (160.38±36.77) min, the intraoperative blood loss ranged from 30 to 85 ml with an average of (53.60±18.98) ml. Tow patients had mild postoperative dysphagia, which improved with symptomatic treatment such as nebulized inhalation. CHE score decreased from (4.05±0.96) preoperatively to (2.40±0.70) at 6 months postoperatively (t=12.97, P<0.05). The number of improved vertigo at 6 months postoperatively was 38, with an improvement rate of 90.5%. NDI score was reduced from (34.43±8.04) preoperatively to (20.76±3.91) at 6 months postoperatively (t=11.83, P<0.05). The cervical curvature Cobb angle improved from (8.04±6.70)° preoperatively to (12.42±5.23)° at 6 months postoperatively (t=-15.96, P<0.05). The ACDF procedure has outstanding clinical efficacy in treating CSA. The operation can rapidly relieve patients' episodic vertigo symptoms by relieving bony compression and reconstructing cervical curvature. However, it is necessary to strictly grasp the indications for surgery and clarify the causes of vertigo in patients, and ACDF surgery is recommended for CSA patients for whom conservative treatment is ineffective.

Induced pluripotent stem cell-derived vascular smooth muscle cells as an in vitro model of coronary spastic angina

Abstract Background Coronary spastic angina (CSA), also known as Prinzmetal’s variant angina, is a form of angina caused by coronary artery spasm. CSA is characterized by enhanced basal tone of coronary artery smooth muscle and hyperreactivity to vasoconstrictor stimuli. The vascular smooth muscle hyperreactivity is likely due to a post-receptorial cellular abnormality in the regulation of myofibril contraction, suggesting the possibility of multiple stimuli acting on various cellular receptors. However, its detailed mechanism is still unclear. To investigate it, various experiments using coronary artery smooth muscle cells obtained from the CSA patients is preferable, but it is impossible to do it clinically and ethically. Purpose The purpose of this study was to establish induced pluripotent stem cell (iPSC)-derived vascular smooth muscle cells (VSMCs) and to characterize this VSMC model for CSA research. Methods Three CSA patients with ST-segment elevation, which is a characteristic of variant angina, were recruited for this study. The isolated skin fibroblasts or peripheral blood mononuclear cells were reprogrammed into iPSCs through electroporation of episomal plasmids encoding the reprogramming genes OCT3/4, SOX2, KLF4, L-MYC, LIN28, and mouse p53DD. We differentiated mesodermal using Glycogen synthase kinase 3 inhibition and Bone morphogenetic protein 4 treatment from iPSCs and resulted in the differentiation of VSMCs by platelet-derived growth factor-BB and Activin A. The differentiation of VSMCs was confirmed by VSMC-specific gene expression in qRT–PCR and fluorescence-activated cell sorting (FACS). We examined biological features and intracellular calcium response to acetylcholine (ACh) in VSMCs obtained from 3 CSA patients and 3 healthy controls. Intracellular free Ca2+ concentration ([Ca2+]i; nM) was measured by fura-2. Results CSA iPSCs were confirmed to have normal karyotypes and pluripotency to differentiate. FACS showed that VSMCs differentiated from iPSCs exhibited smooth muscle cell marker expressions including alpha-smooth muscle actin and SM22-alpha. qRT–PCR showed that VSMCs from iPSCs had expressions of ACTA2 and TAGLN gene similar to the human coronary artery smooth muscle cells. Differentiation induction rate of VSMCs differentiated from iPSCs between CSA and control did not show significant difference. [Ca2+]i at baseline did not differ significantly between them (143 nM in CSA versus 120 nM in control, p=0.63, n=3), but peak increase in [Ca2+]i from baseline after ACh stimulation was significantly increased in CSA group compared with control (372 nM versus 177 nM, p&amp;lt;0.05, n=3). Conclusions iPSC-derived VSMCs obtained from CSA patients showed an enhanced intracellular calcium response to ACh, which is likely responsible for CSA phenotype. Our iPSC-derived VSMC model can be useful for elucidating the mechanism of coronary spasm and developing therapeutic strategy such as drug efficacy.

Defining, Detecting and Assessment of Microstructures in Different Stages of Sleep Apnea Transients Using ECG and EEG Features in CSA and OSA Patients

Defining, Detecting and Assessment of Microstructures in Different Stages of Sleep Apnea Transients Using ECG and EEG Features in CSA and OSA Patients

Transvenous phrenic nerve stimulation for the treatment of central sleep apnea reduces episodic hypoxemic burden

Study objectivesTo determine the effect of transvenous phrenic nerve stimulation (TPNS) on the composition of the nocturnal hypoxemic burden in patients with CSA. MethodsWe analysed oximetry data from baseline and follow-up overnight polysomnograms (PSG) in 134 CSA patients with implanted TPNS randomised (1:1) to neurostimulation (treatment group; TPNS on) or no stimulation (control group; TPNS off) from the remedē System Pivotal Trial. The hypoxemic burden was quantified using a battery of metrics, including the oxygen desaturation index (ODI), the relative sleep time spent below 90% SpO2 (T90) due to acute episodic desaturations (T90desat) and due to non-specific and non-cyclic drifts of SpO2 (T90non-specific). Mean change from baseline is provided. ResultsTPNS titrated to reduce respiratory events significantly reduced the ODI in the treatment group by −15.85 h−1 ± 1.99 compared to the control group, which increased 1.32 h−1 ± 1.85 (p 〈0001) and shortened the relative T90 duration by −3.81 percentage points ± 1.23 vs. 0.49 percentage points ± 1.14 increase (p = 0.012). This shortening of T90 was primarily accomplished by reducing the brief cyclic desaturations (T90desaturation: −4.32 percentage points ± 0.98 vs. 0.52 percentage points ± 0.91, p = 0.0004) while notable non-specific drifts in SpO2 remained unchanged (T90non-specific: 0.18 percentage points ± 0.62 vs. -0.13 percentage points ± 0.57, p = 0.72). ConclusionsTPNS appears to significantly reduce the nocturnal hypoxemic burden due to sleep-disordered breathing, but a considerable nocturnal hypoxemic burden from other sources remains. Further investigations are warranted to identify the best strategy to reduce the nocturnal hypoxemic burden beyond preventing respiratory events.

Hand function is already reduced before RA development and reflects subclinical tenosynovitis

BackgroundClinically suspect arthralgia (CSA) is characterised by arthralgia of small joints and considered a risk stage for development of rheumatoid arthritis (RA). However, it remains unknown if the function of...

0808 Worsening central sleep apnea: A sole diagnostic marker of a brain tumor in a child

Abstract Introduction Central sleep apnea (CSA) in children is a relatively uncommon and under-studied sleep disorder. A small subset of patients may have intracranial anomalies, but clinical presentation varies. We present a case of malignant intracranial tumor diagnosed primarily due to the unusual presentation and progression of CSA. Report of Cases: The presented patient is a 12-year-old developmentally appropriate female with a history of obstructive sleep apnea (OSA) status post adenotonsillectomy at two years of age who presented with snoring without witnessed apnea, sleep interruptions, and unrefreshing sleep. Other sleep-related history was unremarkable. No daytime sleepiness or behavioral or learning concerns were noted. Physical examination was unremarkable with normal growth parameters. Initial diagnostic PSG demonstrated severe OSA with an obstructive apnea-hypopnea index (OAHI) of 16/h and mild CSA (CAI:6.7/h); therefore, PAP therapy was pursued after ruling out adenoid regrowth. However, during the first PAP titration study(incomplete study due to mask intolerance), treatment-emergent central apneas were noted (OAHI: 9.8/h; CAI:25.8/h), which were noted even during the second titration study (OAHI:2.7/h; CAI:59.2/h). Even though ordered earlier, the brain MRI was not performed until after the repeat PSG one year later showed persistence of severe CSA (OAHI of 4.5/h and CAHI of 39.5/h) after much persuasion. Interestingly, snoring had reportedly improved with no daytime symptoms or neurologic complaints. The brain MRI demonstrated compressing brainstem lesion highly suspicious for glioma. The patient was emergently sent to neurosurgical care and had chosen hospice care after a few weeks. Conclusion CSA can be an early or the only finding in patients with brainstem tumors, even before neurologic signs and symptoms. The PSG findings changed from mild CSA to treatment-emergent CSA to severe CSA, possibly with the progression of underlying disease. Close follow-up and ensuring patient compliance are essential in CSA patients. CSA severity should prompt MRI brain even with an intact neurological examination. More research is needed to fully understand the link between cerebral disease and polysomnographic data. This could aid in early diagnosis and treatment. Support (If Any) no conflicting or financial interests to disclose

A Study of Cardiac Autonomic Functions in Patients with Chronic Stable Angina Undergoing Percutaneous Coronary Revascularization.

ObjectiveIn the present study, cardiac autonomic functions in CSA patients were evaluated before and after percutaneous coronary intervention (PCI) using heart rate variability (HRV).MethodsThirty patients with CSA were recruited from cardiology outpatient clinics of VMMC and Safdarjung hospital, New Delhi, India. For each patient HRV parameters (LF, HF, LF:HF ratio, SDNN, RMSSD, total power, and pNN50) were gathered before and after PCI. Data were compiled and analyzed using licensed statistical software: SPSS version 21.0.ResultsOut of 30 subjects, SDNN (61.47±22.27 vs. 32.24±16.50ms, p<0.0001), RMSSD (53.86±31.41 vs. 28.81±23.80ms, p=0.001) and pNN50 (46.24±34.36 vs. 5.20±6.63, p<0.0001) in post-PCI were significantly higher as compared to the pre-PCI values. There were significant increases in both LF (1193ms2±302.04ms2vs. 1054.60ms2±208 ms2, p<0.001) and HF (991.57±872.40ms2vs. 466.72ms2±257.93ms2, p<0.0001), also in total power (3548.37ms2±807.73ms2vs. 2428 ms2±867.07 ms2, p<0.0001) in post-PCI as compared to pre-PCI. The LF:HF ratio in pre-PCI was higher as compared to post-PCI (1.467±1.639 vs. 1.143±0.852, p=0.805), but the difference was not statistically significant.ConclusionIn this preliminary study, it is concluded that there is significant improvement in resting cardiovascular parameters, resting autonomic tone as measured by HRV which shows increase in both parasympathetic as well as sympathetic reactivity following revascularization by PCI in CSA patients. Hence, we also suggest that the use of noninvasive tests such as HRV should be done to stratify further risk of disease progression.

Novel frameshift variant (c.409dupG) in SLC25A38 is a common cause of congenital sideroblastic anaemia in the Indian subcontinent

AimsCongenital sideroblastic anaemias (CSAs) are a group of rare disorders with the presence of ring sideroblasts in the bone marrow. Pathogenic variants are inherited in an autosomal recessive/X-linked fashion. The...

Multicentric study comparing cyclosporine, mycophenolate mofetil and azathioprine in the maintenance therapy of lupus nephritis: 8years follow up.

The ideal long-term maintenance therapy of Lupus Nephritis (LN) is still a matter of debate. The present study was aimed at comparing the efficacy/safety profile of cyclosporine (CsA), mycophenolate mofetil (MMF) and azathioprine (AZA) in long-term maintenance therapy of LN. We performed a retrospective study of patients with biopsy-proven active LN. After induction therapy, all patients received maintenance therapy with CsA, MMF or AZA based on medical decision. Primary endpoint was complete renal remission (CRR) after 8years (defined as proteinuria < 0.5g/24h, eGFR > 60ml/min/1.73mq); secondary endpoints were: CRR after 1year, renal and extrarenal flares, progression of chronic kidney disease (CKD stage 3 or above) and side-effects. Out of 106 patients, 34 received CsA, 36 MMF and 36 AZA. Clinical and histological characteristics at start of induction therapy were comparable among groups. At start of maintenance therapy, CsA patients had significantly higher proteinuria (P = 0.004) or nephrotic syndrome (P = 0.024) and significantly lower CRR (23.5% vs 55.5% on MMF and 41.7% on AZA, P = 0.024). At one year, CRR was similar in the three groups (79.4% on CsA, 63.8% on MMF, 58.3% on AZA, P = 0.2). At 8years, the primary endpoint was achieved by 79.4% of CsA vs 83.3% of MMF and 77.8% of AZA patients (P = 0.83); 24h proteinuria, serum creatinine, eGFR were similar. CKD stage 3 or above developed in 8.8% of CsA, in 8.3% of MMF and in 8.3% of AZA patients (P = 0.92). Flares-free survival curves and incidence of side-effects were not different. This is the first study comparing CsA, MMF and AZA on long-term LN maintenance therapy. All treatments had similar efficacy in achieving and maintaining CRR, despite more severe baseline clinical features in patients treated with CsA.

Multisystem analyses of two Cockayne syndrome associated proteins CSA and CSB reveal shared and unique functions

Mutations in the CSA and CSB genes are causative of Cockayne syndrome neurological disorder. Since the identification of indispensable functions of these two proteins in transcription-coupled repair and restoring RNA synthesis following DNA damage, the paradoxical less severe clinical symptoms reported in some CS-A patients have been puzzling. In this study we compared the effects of a CSA or a CSB defect at the levels of the cell and the intact organism. We showed that CSA-deficient zebrafish embryos exhibited modest hypersensitive to UV damage than CSB depletion. We found that loss of CSA can effectively release aggregation of mutant crystallin proteins in vitro. We described the opposite effect of CSA and CSB on neuritogenesis and elucidated the differentiated gene expression pathways regulated by these two proteins. Our data demonstrate convergent and divergent roles for CSA and CSB in DNA repair and transcription regulation and provide potential explanations for the observed differences between CS-A and CS-B patients.

Reduction of sleep-disordered breathing following effective percutaneous mitral valve repair with the MitraClip system.

This study tested the hypothesis that a reduction of pulmonary congestion achieved by a reduction of mitral regurgitation (MR) severity in heart failure (HF) patients is associated with reduced event lengths of sleep-disordered breathing (SDB). We prospectively enrolled 20 consecutive HF patients who underwent MitraClip implantation. Patients underwent cardiorespiratory polygraphic recording prior to and after percutaneous mitral valve repair (PMVR). Beyond routinely established indicators of apneas and hypopneas per hour (respiratory event index), we manually analyzed apnea event lengths. MitraClip implantation led to marked reduction of MR severity and a reduction in left atrial pressure. These hemodynamic changes were accompanied by changes in SDB: the subtype of SDB switched from CSA to OSA in 4 patients. Likewise, quantitative indicators of SDB were altered in both forms of SDB with a reduction in circulatory delay (CSA 38 ± 14 vs. 33 ± 15s.; p = 0.002 and OSA 34 ± 9 vs. 28 ± 6s.; p = 0.02) and a corresponding reduction in ventilation lengths in CSA patients (42 ± 15 vs. 37 ± 13s.; p = 0.05). A reduction of pulmonary congestion as achieved by a decrease of left atrial pressure through successful MitraClip implantation is associated with a reduction in respiratory event lengths, further pointing towards a relation between SDB and HF.

Metastases-yield and Prostate-specific Antigen Kinetics Following Salvage Lymph Node Dissection for Prostate Cancer: A Comparison Between Conventional Surgical Approach and Prostate-specific Membrane Antigen-radioguided Surgery

The first results on 99mTechnetium prostate-specific membrane antigen-radioguided surgery (99mTc-PSMA- RGS) showed promising outcome. Here, we sought to evaluate if this targeted molecular surgical approach might be more effective than conventional salvage lymph node dissection (sLND). We prospectively analysed 42 consecutive patients who underwent sLND based on preoperative 68Gallium (68Ga)-PSMA-positron emission tomography (PET) imaging between 2015 and 2018. In 29 patients, the dissection field was based solely 68Ga-PSMA-PET imaging (conventional surgical approach [CSA]), whereas 13 patients underwent 99mTc-PSMA-RGS. Preoperative characteristics of both groups were similar. Final pathology revealed no metastases in nine CSA patients (31%), whereas all visible lesions on preoperative 68Ga-PSMA-PET were removed in patients who underwent RGS. A PSA decline in general, >50% and >90% within 6 wk was seen in 50%, 29%, and 7% versus 100%, 92%, and 53% in CSA versus RGS groups, respectively (all p<0.01). This is the first comparison of conventional and PSMA-radioguided approach with regards to short-term efficacy of sLND. Although long-term outcome needs to be awaited, RGS offers promising results. Patient summaryWe compared two surgical approaches for lymph node dissection in lymph node only recurrent prostate cancer patients. The radioguided approach was superior in removing the affected lymph nodes, resulting in a more pronounced prostate-specific antigen decline.

Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis.

Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes.The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed.Colony-stimulating factor (CSF)2 protein levels were increased in CSA sputum supernatants, with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene set variation analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated.Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level, with CSA patients having increased CSF2 expression and ESA patients showing sustained loss of epithelial barrier processes.

Clinical observation on cervical chiropractic for cervical spondylosis of vertebral artery type

To observe the curative effect of cervical chiropractic for cervical spondylosis of vertebral artery type (CSA) and to explore its possible mechanism. Sixty CSA patients were randomly divided into two groups. Thirty patients in the treatment group were treated with chiropractic manipulation for cervical vertebrae, once every other day, 7 treatments in total. The other 30 patients in the control group received oral administration of flunarizine hydrochloride, 10 mg per night, for 14 d. Cervical vertigo and functional assessment scale and transcranial cerebral Doppler (TCD) were measured before treatment and 7 days after treatment. The total effective rate was 96.7% in the treatment group and 83.3% in the control group. The curative rate was 66.7% in the treatment group and 20% in the control group. The differences between the two groups in the total effective rate and the curative rate were statistically significant (both P<0.05). The scores of cervical vertigo symptom and functional assessment after treatment in both groups were significantly higher than those before treatment (both P<0.01); the difference between the two groups was statistically significant (P<0.05). After treatment, the maximum systolic velocity (Vs), the maximum diastolic velocity (Vd), the mean velocity (Vm), the pulsatility index (PI) and the vascular resistance index (RI) in both groups were significantly improved compared with those before the treatment (all P<0.01); there were significant differences between the two groups (all P<0.05). Cervical chiropractic is an effective method for CSA, and its curative effect is better than that of flunarizine hydrochloride alone. Its mechanism may relate to correcting cervical instability.

Sleep duration and quality in heart failure patients.

Sleep-disordered breathing (SDB) is highly prevalent in patients with heart failure and reduced left ventricular ejection fraction (HF-REF). SDB is classified as predominant obstructive (OSA) or central (CSA) and may alter sleep duration, sleep quality, and quality of life. This study describes sleep quality and duration in well-characterized cohorts of these patients. Two hundred fifty consecutive patients with HF-REF (NYHA class ≥II, ejection fraction ≤45%) underwent cardiac and pulmonary examination, plus full attended in-hospital overnight polysomnography (PSG). PSG recordings were performed according to current recommendations and underwent independent, blinded analysis at a core laboratory. Patients with HF-REF and CSA were older and had more impaired cardiac function compared to those with OSA. With respect to sleep parameters, patients with CSA spent more time in bed than those with OSA (468±52 vs 454±46min, p=0.021) while sleep efficiency was lower (67±14 vs 72±13% of total sleep time (TST), p=0.008). In addition, CSA patients spent more time awake after sleep onset (101±61 vs 71±46min, p=0.001) and had more stage N1 (light) sleep (33±19 vs 28±16% of TST, p=0.017). Overall, the proportion of sleep spent in N3 (slow-wave/deep) sleep in HF-REF patients with SDB was low (4.1±6.3% of TST) compared with healthy adults. HF-REF patients with CSA compared to OSA have worse sleep efficiency and quality. This could result in less restorative sleep, changes in sympathovagal balance, and impaired resetting of important reflexes, which might contribute to worse cardiovascular outcomes in HF-REF patients with SDB.

Cyclosporine Plus Methotrexate or Cyclosporine Plus Mycophenolate Mofetil as Graft Versus Host Disease Prophylaxis in Acute Leukemia Transplant: Comparison of Toxicity, Engraftment Kinetics and Transplant Outcome.

We sought to compare two graft-versus-host disease (GVHD) prophylaxis regimen, cyclosporine and methotrexate (CsA+MTX) with CsA+mycophenolate mofetil (MMF) in 77 acute leukemia patients who underwent hematopoietic stem cell transplant (HSCT) between January 2008 and March 2013. Fifty-three patients received CsA+MTX while 24 received CsA+MMF. The incidence of grade 3-4 mucositis and grade 3-4 diarrhea was 74 and 6% with CsA+MTX compared to 33% and 21% with CsA+MMF (P=0.001 and 0.09 respectively). Forty-two (79%) patients in CsA+MTX group required total parenteral nutrition compared to 14 (58%) in CsA+MMF group (P=0.09). The incidence of engraftment fever was 17% with CsA+MTX and 41% with CsA+MMF (P=0.02). The median time to neutrophil and platelet engraftment was 14days and 13days with CsA+MTX compared to 12days and 10days with CsA+MMF (P=0.003 and 0.08 respectively). The incidence of any grade and grade II-IV acute GVHD was 45 and 13% with CsA+MTX compared to 42 and 29% with CsA+MMF (P=NS). Incidence of overall and extensive chronic GVHD was 57 and 38% with CsA+MTX compared to 42 and 17% with CsA+MMF (P=NS). Incidence of relapse was 38% with CsA+MTX compared to 33% with CsA+MMF (P=NS). TRM was 6% with CsA+MTX and 21% with CsA+MMF (P=NS). At 2years, overall survival (OS) was 64% in CsA+MTX group compared to 46% in CsA+MMF group (P=NS). We conclude that CsA+MMF is associated with lesser toxicity, faster myeloid engraftment and similar rates of acute and chronic GVHD, TRM, relapse and OS compared to CsA+MTX in acute leukemia transplant.

Development of Chinese version vertigo symptom scale (VSS): reliability and validity

To develop a Chinese version of Vertigo Symptom Scale (VSS-C) and to examine its reliability and validity. The VSS was translated into Chinese and developed a Chinese version VSS (VSS-C) with the consent of the author. The VSS-C scale was tested in 52 subjects with cervical spondylosis of vertebral artery type (CSA group) and 21 healthy subjects (control group). In CSA group VSS-C scale and SF-36 scale investigation was performed for 2 times with 1 week interval, after receiving 1-week orthopedic rehabilitation the patients were evaluated with the VSS-C and SF-36 scale; while subjects in control group received the investigation twice in two weeks. The reliability of the scale was evaluated with Cronbach's alpha method and the correlation between SF-36 scale and the VSS-C were also evaluated for the validity. The internal consistency of VSS-C was good with Cronbach's alpha of 0.886. Test-retest reliability was also very good with an intraclass correlation coefficient (ICC) between two time points, being 0.970 for VSS-C, 0.965 for VSS-AA and 0.992 for the VSS-VER. Regarding concurrent validity, significant low correlation was found between the VSS-AA and VSS-VER (r=0.379, P<0.05). Significant expected correlation was detected between the VSS-C and SF-36 (r>0.5, P<0.05) . The independent-samples t test results (t=6.261, P<0.01) of the CSA group and the control group showed that the VSS-C was able to distinguish healthy people from CSA patients. The paired-samples t test results (t=5.513, P<0.01) showed that VSS-C reflected the improvement of patients after treatment of Chinese massage manipulation. The Chinese version of VSS has a high comprehensibility, internal consistency and validity, and it can be a useful instrument for evaluation of patients with cervical spondylosis of vertebral artery type in China.

Incidence of Development of Obesity After Heart Transplantation According to the Calcineurin Inhibitor

BackgroundDevelopment of obesity after heart transplantation (HT) is a common complication, largely attributed to immunosuppressive therapy. The objective of this study is to compare the incidence of development of obesity after HT, according to the calcineurin inhibitor (CNI) used (cyclosporine [CsA] vs tacrolimus [Tac]). MethodsWe studied 101 consecutive HT patients from November 2006 to December 2010. A diagnosis of overweight–obesity was made by a body mass index of ≥25 kg/m2, which was assessed before HT and at 1 year after HT. Patients were randomly assigned to the administration of CsA or Tac by a simple randomization method using a computer program (56% received CsA and 44% Tac). ResultsOf the 101patients, 77% were men, and ischemic heart disease was the most common indication for HT. At baseline, there were no differences in weight between groups treated with CsA or Tac. The mean weight for each group was 71.5 ± 12 and 75 ± 14 kg, respectively (P = .2). The weight increase was greater among CsA patients: after HT, the weight gain was 6.9 ± 11 kg in the CsA group, whereas a minimal weight loss of 0.03 ± 14 kg (P = .008) was experienced in the group treated with Tac. The multivariate analysis showed that only CsA treatment was an independent predictor of development of obesity 1 year after HT (odds ratio, 3.84; 95% CI, 1.04–14.21; P = .01). ConclusionWeight gain after HT may be related to the CNI used and CsA seems to be the CNI that produces the greatest increase.

A Profound Decrease in FoxP3+Helios+CD4+ T Cells in a Subset of Patients with Acquired Aplastic Anemia and Pure Red Cell Aplasia: A Common Mechanism Underlying a Dependency on Cyclosporine

Background: A subset of patients with acquired aplastic anemia (AA) require low-dose cyclosporine (CsA) to maintain good hematopoietic function even after achieving a remission with immunosuppressive therapy (IST). Such CsA-dependent AA offers opportunities to clarify the immune mechanisms underlying bone marrow (BM) failure, but little is known about the mechanism(s) underlying this condition except for its close association with a particular HLA-class II allele DRB1*15:01. Regulatory T cells (Tregs), defined as CD4+CD25highFoxP3+ T cells, have been shown to be decreased in patients with severe AA at diagnosis and to recover to normal levels in association with hematological recovery after successful IST. An insufficient Treg recovery may account for dependency on CsA in a particular subset of AA patients, and also in patients with idiopathic pure red cell aplasia (PRCA), another typical immune-mediated BM failure of which remission is known to depend on CsA in virtually all patients. To test this hypothesis, we determined the percentage and absolute number of Tregs, as well as Th1, Th2 and Th17 cells, in various types of immune-mediated BM failure, using an anti-FoxP3 antibody (Ab) and anti-Helios Ab that allows enumeration of the functional Tregs more precisely than conventional methods. Methods: Different CD4+ Treg subsets were enumerated using a multicolor flow cytometry assay. Peripheral blood mononuclear cells (PBMCs) were stimulated by phorbol myristate acetate (PMA) and ionomycin in the presence of monensin for four hours, then were subjected to flow cytometry to determine the percentage of CD4+ T cells positive for cytoplasmic interferon-γ (Th1), interleukin 4 (Th2) and interleukin 17 (Th17). CsA-dependent AA was defined as AA with two or more episodes of relapse of pancytopenia that occurred during more than one year of therapy, followed by a good response to CsA. All six patients with CsA-dependent AA had normal blood cell counts and HLA-DR15 (DRB1*15:01 in five and DRB1*15:02 in one). Results: The normal ranges of each T cell subset percentage and the absolute numbers determined in 47 healthy volunteers (HVs) were: FoxP3+Helios+ Tregs 6.5±1.6%/ 47.7±13.8/µl, Th1 22.3±6.6%/ 151.2± 45.5/µl, Th2 5.5±1.6%/ 38.3±170.9/µl and Th17 1.7± 0.7%/ 11.2± 4.7/µl. The expression of FoxP3 by CD4+ T cells decreased with time after sampling, and this assay therefore necessitated analyses within 16 hours after sampling using fresh PBMCs. Compared to healthy volunteers, the percentage and absolute number of FoxP3+Helios+ Treg cells were significantly lower in the five patients with severe AA at diagnosis (3.7±1.1%, 22.7±6.8/µl) and in six CsA-dependent AA patients (3.4±0.8%, 13.8±12.3/µl) (Figure). In contrast, the Treg percentages were comparable to those of the HVs in four AA patients on CsA in convalescence (5.8±1.0%) and nine patients in remission off CsA (6.3±1.1%) while the absolute numbers of FoxP3+Helios+Tregs (27.3±19.2/µl, 32.3±13.3/µl) in these groups were lower than those of the HVs. On the other hand, the percentages of all other CD4+ T cell subsets were comparable among the four different groups and HVs. The apparent decrease in FoxP3+Helios+ Tregs despite normal blood cell counts in patients with CsA-dependent AA prompted us to screen nine patients with idiopathic PRCA whose erythropoietic functions were all dependent on CsA. The FoxP3+Helios+ Tregs were decreased in both the percentage and absolute count (3.1±0.5%, 12.1±5.9/µl) in all of these patients, including two patients whose PBMCs were examined before CsA therapy. As a result, the ratios of Th1/Treg and Th17/Treg were markedly higher in newly-diagnosed AA (12.5±3.4, 0.9±0.8), CsA-dependent AA (12.6±12.1, 1.1±1.5) and PRCA (10.6±7.7, 0.7±0.3) patients than in AA patients in convalescence (6.1±4.3, 0.4±0.1) and those in remission (3.8±2.3, 0.4±0.2), which were comparable to the HVs Th1/Treg and Th17/Treg ratios (3.3±0.9, 0.3±0.2). Conclusions: Decreased percentages and absolute counts of Tregs, as well as increased Th1/Treg and Th17/Treg ratios, are common features in patients with CsA-dependent AA and PRCA. A persistent decrease in Tregs may serve as a good marker for predicting AA relapse in patients responding to CsA. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Final Results From the Long-Term Extension (LTE) of the Belatacept Phase 2 Study in Kidney Transplantation.

Background: At 5 years post-transplant, data from the Phase 2 IM103-100 LTE study of belatacept in kidney transplantation demonstrated a favorable safety profile and improved renal function vs cyclosporine (CsA) (Vincenti F et al, JASN 2010;21(9):1587-96). The safety and efficacy of belatacept up to study closure (9-11 years follow-up) is reported herein. Methods: 218 patients were randomized to receive a more or less intensive regimen of bela (n=145) or CsA (n=73), with bela patients receiving treatment at 4- or 8-week intervals (5 mg/kg after 6 months). Here we focus on the results of the 44 bela patients who remained in the LTE cohort until study end; too few CsA patients (n=9) remained at the end of the study to make comparisons between groups. Results: The 44 patients remaining in the bela group at study end received treatment for a mean of 9.7 years. From randomization to end of study, 25% of patients missed no infusions, and 21% missed only 1 infusion. There were no deaths or graft losses in this cohort. From randomization to study end, 84% of bela patients had serious AEs, 36% had serious infections, and 23% had malignancies. There were no cases of PTLD in this cohort. In the pooled bela cohort, mean(SD) MDRD cGFR was 70(21) mL/min/1.73m2 at Month 3 and 72(17) mL/min/1.73m2 at the end of the study (Figure). From randomization to study end, there was 1 acute rejection episode (Banff grade IIA), occurring in Year 9 in a patient randomized to the 8-week dosing interval group. Conclusions: Data suggest that the profile of belatacept is consistent over approximately 10 years of treatment: patients maintained renal function with no new safety findings and there was high treatment compliance. However, the sample sizes are limited in this self-selecting cohort, therefore results should be interpreted with caution.Figure: No Caption available.DISCLOSURE:Blancho, G.: Speaker’s Bureau, Novartis, Roche. Jones-Burton, C.: Employee, Bristol-Myers Squibb. Vincenti, F.: Grant/Research Support, Bristol Myers Squibb, Alexion, Pfizer, Astellas, Novartis, Genentech.