Bone marrow mononuclear cell therapy in ischaemic stroke: a systematic review.

Bone marrow mononuclear cell (BM-MNC) therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review of published studies using BM-MNC therapy in patients with ischaemic stroke (IS). Literature was searched using MEDLINE, PubMed, EMBASE, Trip Database, Cochrane library and clinicaltrial.gov to identify studies on BM-MNC therapy in IS till June, 2016. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta-analysis. We included non-randomized open-label, single-arm and non-randomized comparative studies or randomized controlled trials (RCTs) if BM-MNCs were used to treat patients with IS in any phase after the index stroke. One randomized trial, two non-randomized comparative trials and four single-arm open-label trials (total seven studies) involving 227 subjects (137 patients and 90 controls) were included in the systematic review and meta-analysis. The pooled proportion for favourable clinical outcome (modified Rankin Scale score ≤2) in six studies involving 122 subjects was 29% (95% CI 0.16-0.43) who were exposed to BM-MNCs and pooled proportion for favourable clinical outcome of 69 subjects (taken from two trials) who did not receive BM-MNCs was 20% (95% CI 0.12-0.32). The pooled difference in the safety outcomes was not significant between both the groups. Our systematic review suggests that BM-MNC therapy is safe up to 1 year post-intervention and is feasible; however, its efficacy in the case of IS patients is debatable. Well-designed randomized controlled trials are required to provide more information on the efficacy of BM-MNC transplantation in patients with IS.

High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis.

Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database 'PubMed', 'EMBASE', and 'Google Scholar' as well as from many trial databases. The following search terms were used: 'Statin therapy' AND 'Cardiovascular Disease', AND 'Dose' AND 'Intracerebral hemorrhage', AND 'Randomized Controlled Trials' AND 'High Dose Statin'. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed-effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random-effect model was used. Begg's funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high-dose statin and 31,105 subjects receiving placebo were analyzed in our meta-analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16-2.01; P = 0.002). There was no difference in all-cause mortality between the two groups (RR = 0.95; 95% CI: 0.86-1.06; P = 0.36). No publication bias was observed through Begg's funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings.

Targeting the endothelin axis in scleroderma renal crisis: rationale and feasibility.

BACKGROUND: We have studied endothelin-1 (ET-1) levels and ET-1 ligand and receptor tissue expression in scleroderma renal crisis (SRC) and undertaken a pilot open label safety study of bosentan, a non-selective ET-1 receptor antagonist, in SRC [Bosentan in Renal Disease-1 (BIRD-1)]. METHODS: Serum levels of ET-1 were measured in healthy controls (n = 20) or systemic sclerosis (SSc) (n = 80) with or without SRC, including cases of pulmonary arterial hypertension (PAH). Renal biopsies (n = 27) from patients with SRC were stained for endothelin ligand and receptors. Six cases of SRC received 6 months bosentan. Outcome measures were compared with SRC cases managed at our centre from 2000 to 2004 (n = 49). RESULTS: Serum ET-1 was elevated in SRC but less than in PAH. ET-1 and both endothelin A and endothelin B receptor expression was increased in SRC biopsies in glomeruli, interstitium and hallmark vascular lesions of SRC. In the BIRD-1 cohort, serum ET-1 was elevated in all cases at SRC (median healthy controls 0.50 pg/ml; SRC 1.48 pg/ml; P < 0.0005), and increased further with bosentan therapy (1.46 vs. 3.05 pg/ml; t-test P < 0.05). Bosentan was well tolerated with no significant drug-related serious adverse events and long-term outcomes were favourable compared with historic cases. Three patients developed rebound hypertension on withdrawal of bosentan and one appeared to further benefit from maintenance therapy. CONCLUSION: Upregulation of ET-1 ligand axis suggests that ET-1 receptor blockade is logical and treatment with bosentan appears to be safe in SRC. Future studies to assess therapeutic benefit and compare selective or non-selective receptor antagonists are justified.

A case of systemic nocardiosis in systemic vasculitis and a review of the literature.

Systemic nocardiosis is rarely reported in patients with systemic vasculitis, and is mostly described in patients experiencing long-term immunosuppression following organ transplantation. In this report, we describe a 71-year-old man who developed disseminated Nocardia infection during treatment of his underlying microscopic polyangiitis. He had no other associated risk factors. This case highlights the importance of considering rare pathogens in immunosuppressed patients who present with nonspecific symptoms, as well as the impact of such pathogens on clinical management.

Long-term relapse-free rurvival rate and predictive factors of idiopathic thrombocytopenic purpura in adults undergoing splenectomy.

BACKGROUND: Our aim is to identify the long-term relapse-free rate and predictive factors of response to splenectomy in adults with idiopathic thrombocytopenic purpura (ITP). METHODS: Between 1999 and 2005, 54 patients of ITP, who underwent splenectomy in Chang Gung Memorial Hospital, Linkou, Taiwan were retrospectively reviewed. Various pre, intra and postoperative factors were analyzed to determine the predictive factors of response and long-term disease-free rate after splenectomy in adult patients. RESULTS: The relapse free survival rates in complete response patients of splenectomy at 1-, 3- and 5-yr are 91.9%, 88.4%, and 88.4%, respectively. Younger age, response to steroids, pre- and postsplenectomy high platelet counts were found to be have significant p value of < 0.05 as predictive factors in univariate analysis. In multivariate analysis, only pre-op and post-op platelet counts were significant. CONCLUSIONS: Significant long-term relapse-free survival rate is achieved by splenectomy in adults with ITP. In univariate analysis, age, response to steroids, pre- and postsplenectomy platelet counts were the significant predictive factors of response. But in multivariate analysis, only pre-op and post-op platelet counts were significant.

Antisense inhibition of S6 kinase 1 produces improved glucose tolerance and is well tolerated for 4 weeks of treatment in rats.

p70 Ribosomal S6 kinase 1 (S6K1) is implicated in the pathogenesis of type 2 diabetes as knockout mice are hypoinsulinemic, hypersensitive to insulin treatment and are less susceptible to obesity-induced insulin resistance. Although S6K1 knockout mice provide important information on the biology of this target, the therapeutic relevance of S6K1 inhibition in adult animals is unknown. Thus, this research evaluated the potential safety and efficacy of S6K1 inhibition using antisense oligonucleotides (ASO) in mature Sprague-Dawley rats. Male rats treated with S6K1 ASO (25 or 50 mg/kg, 2×/week × 4 weeks) had a marked reduction (>90%) of S6K1 mRNA in the liver and epididymal fat and no effect on hepatic S6K2 expression. The decrease in S6K1 mRNA translated to decreased (>80%) S6K1 protein and kinase activity in the liver at the 50-mg/kg dose. The animals tolerated the S6K1 treatment well with no signs of clinical toxicity. A reduction in body weight gain was observed within 2 weeks of S6K1 ASO treatment. At 4 weeks, body weight gain was reduced by up to 25% in the 50 mg/kg group with a commensurate decrease (14%) in food consumption. A decrease in heart weight in the 50 mg/kg group was observed and not associated with cardiac injury or dysfunction. In an oral glucose tolerance test, S6K1-ASO-treated animals demonstrated a dose-dependent improvement in systemic glucose utilization and had reduced fasting insulin levels. Hepatic gene microarray analysis identified dose-dependent elevations in igfbp1, acss2 and acat2 gene expression in S6K1-ASO-treated animals. These results suggest that inhibition of S6K1 for up to 4 weeks may be therapeutically relevant to induce insulin sensitization and attenuate weight gain with low risk for serious toxicity.

Pathological examination of 12 regional lymph nodes and long-term survival in stages I-III colon cancer patients: an analysis of 2,056 consecutive patients in two branches of same institution.

PURPOSE: Pathologic examination of at least 12 lymph nodes (LNs) is widely accepted as a standard for colon cancer surgery. We sought to address its association with patient source, other clinicopathological factors, and survival by comparing information from two branches in a large single institution. METHODS: Patients with stages I-III adenocarcinoma of the colon between 1998 and 2003 were identified from the Chang Gung Colorectal Tumor Registry in two branches (Linkou and Kaohsiung branches) of same institution. We used multivariate analysis to adjust for variables with P < 0.1 in univariate analyses. RESULTS: A minimum of 12 examined nodes were observed in 80% of patients in Linkou branch versus 25% in Kaohsiung branch (P < 0.0001). Younger age, right hemicolectomy, larger tumor, higher tumor stage, higher caseload of surgeons, and patients at Linkou branch with an odds ratio (OR) as high as 23 (95% CI, 17-31) were independently associated with a higher frequency of ≥12 examined nodes. Patients with examined node number of <12 had a greater risk of recurrence within stages II and III (stage II: adjusted OR 1.88, 95% CI 1.27-2.79; stage III: adjusted OR 1.58, 95% CI 1.15-2.17) but not within stage I (OR 0.73, 95% CI 0.23-2.24). CONCLUSIONS: The results confirm that factors influencing nodal harvest are multifactorial and the examined LN number of 12 or more is associated with an increased long-term survival in stages II-III colon cancer. It is possible to adequately sample and examine a sufficient number of nodes in the majority of colon cancer specimens by standardized conventional methods.

Prognosis and feasibility of en-bloc vascular resection in stage II pancreatic adenocarcinoma.

AIM: To establish the prognosis and feasibility of en-bloc vascular resection of stage II pancreatic adenocarcinoma of the head and uncinate process. METHODS: We retrospectively analyzed 87 patients with stage II pancreatic adenocarcinoma, who were subjected to pancreaticoduodenectomy (PD) and pylorus-preserving PD (PPPD) between 1996 and 2006 in Chang Gung Memorial Hospital, Taiwan. Twelve and 75 patients underwent PD/PPPD with and without resection of portal vein/superior mesenteric vein (PV/SMV), respectively. RESULTS: The overall 1- and 3-year survival rates of patients undergoing PD/PPPD with and without vascular resection were 50.0% and 16.7%, and 44.4% and 12.2%, respectively. Morbidity and mortality rates in the PV/SMV resection vs non-resection group were 50.0% and 0.0%, and 40.0% and 2.7%, respectively. In multivariate analysis, serum bilirubin, histological differentiation and adjuvant chemotherapy were independent prognostic factors that influenced survival. CONCLUSION: In stage II adenocarcinoma of the pancreatic head and uncinate process, serum bilirubin, histological differentiation and adjuvant chemotherapy were independent prognostic factors, and en-bloc vascular resection is a feasible option in carefully selected patients.

Split-liver transplantation in 2 adults: significance of caudate lobe outflow reconstruction in left lobe recipient: case report.

Split-liver transplantation is a well-known procedure for increasing the donor pool. The procedure is commonly used in 1 adult and 1 child, but is less commonly performed in 2 adults because of technical difficulty and poor outcome in left-lobe recipients. Preservation of caudate lobe function is important in recipients with borderline graft-recipient weight ratio to achieve better results. Herein, we report a case in which caudate lobe outflow was reconstructed in a left lobe with a caudate lobe graft in split-liver transplantation in 2 adults.

Hydrocoele of a femoral hernia sac.

Hydrocoele of a femoral hernia sac is an extremely rare entity. Extensive literature review and Internet searching revealed only a few authentically reported cases. It mostly occurs in females during the fourth to sixth decades of life. The most common clinical presentation is groin swelling. It is diagnosed as an irreducible or incarcerated femoral hernia or subcutaneous lipoma. In almost all of the reported cases, the diagnosis of hydrocoele of a femoral hernia sac has been made only after surgical exploration. The present case is a 40-year-old lady who presented with a painless lump in the right groin and was diagnosed as a case of hydrocoele of a femoral hernia sac only after exploration.

Factors influencing long-term survival in patients with T3 gallbladder adenocarcinoma.

PURPOSE: This study aimed to identify the factors influencing the surgical outcome in patients with T3 gallbladder adenocarcinoma (GBA). METHODS: Between 1996 and 2006, 100 GBA patients who underwent surgical treatment in Chang Gung Memorial Hospital, Taiwan, were retrospectively reviewed. Among them, 39 patients with pathological stage T3 GBA were analyzed statistically in terms of demographic data and clinicopathological features. RESULTS: The 1-, 3- and 5-year survival rates for patients with T3 GBA undergoing surgical treatment were 53.5, 37.0 and 32.9%, respectively. Univariate survival analysis revealed male gender, low serum carcinoembryonic antigen (CEA) level, and curative resection as factors which predicted favorable overall survival for T3 GBA patients. Multivariate survival analysis revealed low preoperative CEA levels and curative resections independently predicted favorable outcomes. CONCLUSIONS: Negative resection margin and serum CEA levels were found to be the independent prognostic factors in predicting long-term survival in patients with T3 GBA, and the serum CEA level was also found to be an independent prognostic factor in predicting the long-term prognosis of T0-T4 GBA; however, the result is preliminary due to the limited number of patients. Further studies with a large number of patients are necessary to confirm our result.

Prevention of vascular damage in scleroderma and autoimmune Raynaud's phenomenon: a multicenter, randomized, double-blind, placebo-controlled trial of the angiotensin-converting enzyme inhibitor quinapril.

OBJECTIVE: To evaluate the efficacy and tolerability of prolonged administration of quinapril, a long-acting angiotensin-converting enzyme inhibitor, in the management of the peripheral vascular manifestations of limited cutaneous systemic sclerosis (lcSSc) and in the prevention of the progression of visceral organ involvement in the disease. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study evaluating quinapril 80 mg/day, or the maximum tolerated dosage, in 210 patients with lcSSc or with Raynaud's phenomenon (RP) and the presence of SSc-specific antinuclear antibodies. Treatment was for 2-3 years. The primary outcome measure was the number of new ischemic ulcers appearing on the hands; secondary measures were the frequency and severity of RP attacks, skin score, treatments for ischemia, health status (measured by the Short Form 36 instrument), measures of kidney and lung function, and echocardiographic estimates of pulmonary artery pressure. An intent-to-treat analysis was used. RESULTS: Quinapril did not affect the occurrence of digital ulcers or the frequency or severity of RP episodes. It did not alter the treatments that were prescribed for either infected ulcers or severe RP symptoms. There was no apparent effect on the estimated tricuspid gradient. Health status was not affected by quinapril, and one-half of the patients who believed they had benefited from the trial treatment were in the placebo arm. Quinapril was not tolerated by one-fifth of the patients, with dry cough being the most frequent side effect. CONCLUSION: Administration of quinapril for up to 3 years had no demonstrable effects on the occurrence of upper limb digital ulcers or on other vascular manifestations of lcSSc in this patient population.

Renal MALToma: an unusual lymphoma in a patient with lupus.

Non-Hodgkin's Lymphomas (NHL) have been reported in association with autoimmune disorders particularly Sjogren's syndrome. We report a case of renal MALToma, an unusual NHL in an 84-year-old Caucasian lady with long-standing, non-aggressive Systemic Lupus Erythematosis with no associated Sjorgen's syndrome and who never received cytotoxics.

Pancake kidney detected on renal scintigraphy.

Pancake kidney is an extremely rare renal anomaly resulting from abnormal renal ascent and subsequent fusion. The authors describe a patient with pancake kidneys detected on a Tc-99m DTPA scan. The case reported depicts the scintigraphic findings in such a patient having a pancake kidney.

Nasal Wegener's and skin sarcoid--a rare combination of two granulomatous diseases.

Wegener's granulomatosis (WG) and sarcoidosis are two distinct granulomatous diseases characterized by multisystem involvement. We report a patient who initially presented with symptoms of limited WG predominantly affecting the nose, followed by a facial rash, which was histologically proven to be due to sarcoidosis. The sequential development of these two diseases in one patient is very rare, and to our knowledge, only one such case has been reported in the last 50 years (Am J Kidney Dis 28:893-898, 1996).