Gold: an old drug still working in refractory pemphigus

BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris.     

Improved, low-cost selective culture medium for Actinobacillus actinomycetemcomitans

Actinobacillus actinomycetemcomitans is considered to be one of the major oral putative pathogens, especially in cases of juvenile periodontitis. This microorganism requires nutritionally complex media for growth, and therefore the media for its primary isolation usually include blood agar or serum in their base. In this study we present a new medium, Dentaid-1, which improves the detection of A. actinomycetemcomitans in periodontal samples. In its composition, blood and serum have been omitted, hence reducing its cost and making it a more restrictive medium against the growth of other microorganisms with high nutritional requirements. The growth yields of pure cultures of the bacteria on Dentaid-1 were comparable to those on nonselective blood agar. Moreover, clinical efficacy was evaluated in subgingival samples from 77 subjects with adult periodontitis. Dentaid-1 detected A. actinomycetemcomitans in 24 subjects, while a previously described tryptic soy-serum-bacitracin-vancomycin agar detected the microorganism in only 19 subjects (79.1%). Dentaid-1 is a low-cost, noninhibitory formula for the improved diagnosis and monitoring of patients subgingivally infected by this important oral putative pathogen.     

Improved outcomes and complications of atrial fibrillation catheter ablation over time: learning curve, techniques, and methodology

Introduction and objectives

The outcomes of atrial fibrillation ablation procedures vary widely between different centers. Our objective was to analyze the results and complications of this procedure in our center and identify factors predicting the efficacy and safety of atrial fibrillation ablation.

Methods

In total, 726 atrial fibrillation ablation procedures were performed in our center between 2002 and 2009. Beginning in January 2008, a protocol for anticoagulation and conscious sedation was systematically applied. Outcomes and complications could therefore be compared in 2 well-differentiated groups: group A included 419 procedures performed prior to 2008 and group B included 307 procedures completed after 2008 using the new protocol.

Results

During an average follow-up of 8.7 months, 60.9% of patients were arrhythmia-free after one or repeat procedures. After only 1 procedure, the success rate was 41% and significantly higher in group B (51.6% vs 35.2% in group A; P=.001). There were 31 major complications (4.2%), 26 in group A (6.2%) and 5 in group B (1.6%) (P=.002). The implementation of the new protocol was an independent predictor of the absence of complications (odds ratio=0.406; 95% confidence interval, 0.214-0.769; P<.006).

Conclusions

Systematic application of an anticoagulation and conscious sedation protocol is associated with improved results and fewer complications of atrial fibrillation ablation. Factors not evaluated in the present study, such as operator experience and ongoing improvements in atrial fibrillation ablation technology, could have influenced these findings.Full English text available from:www.revespcardiol.org     

Novel and atypical splicing mutation in a compound heterozygous UNC13D defect presenting in Familial Hemophagocytic Lymphohistiocytosis triggered by EBV infection

Familial Hemophagocytic Lymphohistiocytosis type 3 (FHL3) is a genetic disorder caused by mutations in UNC13D gene, coding the granule priming factor Munc13-4 that intervenes in NK and T cell cytotoxic function. Here we report the case of a 17-month-old girl with prolonged symptomatic EBV infectious mononucleosis and clinical symptoms of hemophagocytic syndrome. In vitro functional analysis pointed to a degranulation defect. The genetic analysis of UNC13D gene identified initially a heterozygous mutation (c.753 + 1G > T) in the donor splice-site that resulted in exon 9 skipping (maternal allele). Mutations in other genes were considered, but additional analysis of UNC13D cDNA revealed in the paternal allele a heterozygous transition from G to A (c.2448 − 13G > A) at the 3′ acceptor splice-site in intron 25, generating a new acceptor splice-site that leads to a frameshift and a premature STOP codon. Allele specific amplification of the cDNA confirmed the absence of a functional mRNA from the paternal allele. This case illustrates an atypical compound heterozygous UNC13D mutation affecting the RNA splicing that generates a typical FHL3 phenotype.     

Pneumocystis jirovecii pneumonia in a patient with pustular psoriasis with an IL‐36RN deficiency treated with infliximab: Case report and review of the literature

Pneumocystis jirovecii pneumonia (PCP) is a relatively rare complication in non‐HIV patients receiving immunosuppressive treatment. Since the introduction of tumour necrosis factor‐α inhibitors cases of this complication have increased. We report the case of a 54‐year‐old, HIV‐negative patient, who presented to our department with a long history of pustular psoriasis with poor response to traditional treatments. During the last admission he developed a severe flare that was unresponsive to cyclosporine, therefore infliximab was initiated. After the third dose he developed PCP that required admission to the intensive care unit, with a positive response to i.v. administration of trimethoprim/sulfamethoxazole. During follow up a mutation in the IL36RN gene compatible with an IL‐36RN deficiency was found and anakinra was started, with rapid improvement of his psoriasis. PCP is a severe complication in patients receiving immunosuppressive therapy and is probably underreported by dermatologists. There are no clinical guidelines for PCP prophylaxis in dermatological patients who will receive immunosuppressive or biological treatments. We believe that it is necessary to report the cases of PCP to assess the real impact of this complication and develop appropriate prophylaxis guidelines.     

Renal allograft rupture: surgical treatment by renal corsetage with lyophilized human dura

We report 5 cases of renal allograft rupture in which diagnosis was established early through clinical data, laboratory tests and echography. Immediate surgery confirmed the suspicion in all cases. Acute rejection was present in 4 patients and in 1 the previous surgical puncture from the perirenal collection demonstrated serohematic fluid with a biological character similar to that of lymph. This latter case seemed to confirm the suspicion that any process associated with edema in a kidney with obstructed lymphatic tracts (meticulous lymphatic ligatures during donor extraction) is capable of causing a rupture. Conventional surgical treatment is dangerous and insecure on an edematous and friable kidney, resulting in a nephrectomy rate of 55.7 per cent and a postoperative death rate of 8 per cent. Hematoma evacuation, hemostasis by local compression and tridimensional containment of the ruptured areas should be the principles of this operation. By means of renal corsetage with lyophilized human dura these principles can be achieved. This surgical technique, which is simple and secure, its variations and future possibilities are described. In 3 of our 5 patients corsetage with lyophilized human dura was applied. All 5 grafts have taken. Renal function is good in 3 cases and acceptable in 2 at followup between 2 and 15 months.     

Interleukin 28B-related polymorphisms: A pathway for understanding hepatitis C virus infection?

AIM:To analyze the role of rs12979860 and rs8099917polymorphisms in hepatitis C virus(HCV)genotype 1infection of Brazilians.METHODS:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C(CHC)who had completed a 48-wk regimen of pegylated-interferonα-2a or-2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and199 healthy blood donors(controls)from a single site between January 2010 and January 2012.Data on the patients’response to treatment was collected.Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin(IL)28B gene fragment encompassing the single nucleotide polymorphisms(SNPs)rs12979860(C/T)and rs8099917(T/G)was carried out for 79 of the CHC patients and 199 of the controls.Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.RESULTS:SNP rs12979860 genotyping was successful in 99.5%of the controls and 97.2%of the CHC patients,whereas the SNP rs8099917 genotyping was successful in 95.5%of the controls and 100%of the CHC patients.The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups,with significantly higher genotype frequencies of CC and TT in the controls(P=0.037 and 0.046,respectively)and of TT and GG in the CHC patients(P=0.0009and 0.0001,respectively).Analysis of the CHC patients who achieved sustained virological response(SVR)to treatment(n=55)indicated that the rs12979860 C allele and CC genotype were predictors of SVR(P=0.02).No significant correlation was found between rs8099917 genotypes and treatment response,but carriers of the T allele showed significantly higher rates of SVR(P=0.02).Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917(P=0.07).CONCLUSION:The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCVinfected individuals may indicate a potential pro