The role of mycophenolate mofetil in kidney transplantation revisited

Since its regulatory approval in 1995, mycophenolate mofetil (MMF) has largely replaced azathioprine (AZA) as the anti-metabolite immunosuppressive of choice in kidney transplantation. While the initial industry-sponsored clinical trials suggested strong reductions in the incidence of acute rejection in the first six months post transplantation, long-term follow-up studies have failed to demonstrate a similar degree of benefit in overall graft and patient survival. In addition, several subsequent studies have raised questions on the potential attenuating effects of calcineurin inhibitor choice on MMF efficacy when compared to AZA. This review will revisit the question of whether the available evidence continues to support the superiority of MMF over AZA in kidney transplantation outcomes while comprehensively reviewing the available evidence from clinical trial data, systematic reviews, and registry studies.     

Rotational dislocation of the thoracolumbar spine. Case report and review of the literature

The authors report a rare case of rotational dislocation of the thoracolumbar spine in a 12-year-old girl with neurofibromatosis Type 1. The patient had progressive spinal kyphoscoliosis with acute-onset paraplegia. She was treated with corrective traction preoperatively, followed by spinal decompression and circumferential spinal fusion without instrumentation. She had complete neurological recovery after a solid fusion of her spine.     

Hair Toe Tourniquet Syndrome in a Four-year-old Boy

Background

Hair toe tourniquet syndrome is a condition in which a hair or thread encircles a digit and results in acute digital ischemia. It usually occurs in children under the age of 1 year. Prompt recognition and surgical removal of the constricting material can save the digit from irreversible tissue necrosis and the loss of digit.

Case Report

We report the first known case of hair toe tourniquet syndrome in a 4-year-old child, who had successful diagnosis and treatment of this condition.

Conclusion

We suggest that hair toe tourniquet syndrome should be considered as a cause of acute digital swelling and discoloration in children of all ages.     

Case Report: Real-Time Polymerase Chain Reaction in Stool Detects Transmission of Strongyloides stercoralis from an Infected Donor to Solid Organ Transplant Recipients

Solid organ transplant recipients can acquire Strongyloides stercoralis from an infected donor. The diagnosis of S. stercoralis in immunocompromised individuals may be challenging due to a lower sensitivity of available parasitological and serological methods, compared with immunocompetent individuals. Recently, a real-time polymerase chain reaction (RT-PCR) in stool has been developed for S. stercoralis diagnosis. We report two cases of S. stercoralis infection transmitted by a donor to two solid organ transplant recipients, who were diagnosed with RT-PCR in stool. This test could play an important role in S. stercoralis diagnosis in immunosuppressed patients, facilitating rapid treatment initiation and reducing the risk of severe strongyloidiasis. Adherence to current recommendations of screening among donors and recipients from endemic areas is also urgently needed.     

Application of real-time PCR for the detection of Strongyloides spp. in clinical samples in a reference center in Spain

Strongyloidiasis is one of the major intestinal helminthic infections in humans with a worldwide distribution, affecting especially tropical and subtropical regions. This disease can occur without any symptoms or as a potentially fatal hyperinfection or disseminated infection. Definitive diagnosis of Strongyloides stercoralis infection relies mainly on demonstration of larvae in stool, but at present there is no gold standard for this diagnosis. Our main objective was to evaluate a real-time PCR targeting the 18S rRNA gene of Strongyloides spp. and to compare it with routine parasitological methods. DNA from Strongyloides venezuelensis was used to optimize PCR protocols obtaining an analytical sensitivity of 0.1 pg of parasite DNA per sample. Sensitivity and specificity of real-time PCR on fecal samples from 231 patients screened for suspected strongyloidiasis attending two hospitals in Madrid were 93.8% and 86.5%, respectively. No significant differences were found when comparing Ct-values of positive PCR between parasitological positive and negative samples. This study showed that real-time PCR is an effective tool for diagnosing strongyloidiasis and could be applied in association with parasitological methods in epidemiological studies in endemic areas. It would be also important to assess its performance in immunocompromised populations who are at risk of fatal disease.     

Open grade III “floating ankle” injuries: a report of eight cases with review of literature

Introduction “Floating ankle” injuries result from high-energy trauma and are usually associated with extensive soft tissue damage. Such rare and complex injuries in the acute phase pose therapeutic dilemma to the treating surgeon. When salvage instead of amputation is preferred, a variety of treatment options are available ranging from open reduction along with minimal internal fixation to external fixation. In this retrospective case series study we report eight patients with open “floating ankle” injuries who had been treated with external fixation with or without internal fixation. Materials and methods Eight consecutive patients (7M: 1F) with mean age of 28 years (range 18–35 years) were treated. All had Grade III open fractures of the distal tibia with foot fractures and various degrees of soft tissue injuries. ISS and MESS were used to assess injury severity. Immediate radical wound debridement; skeletal stabilization and early soft tissue coverage were done by combined trauma and plastic surgical services followed by standard post-operative rehabilitation. All the patients were assessed with SF-36 questionnaire at mean follow-up of 2.5 years (range 2–4 years). Results Three patients were treated primarily with Ilizarov ring fixators, one had hybrid fixation and the other four had Hoffman frames. Four patients needed further surgeries. One patient developed metatarsal osteomyelitis, which was debrided and treated with antibiotics. The SF-36 results were compared with age matched UK norms for men and women in all categories. Only two patients returned to their previous employment. Six suffered varying degrees of disability out of which one underwent amputation. Conclusions External fixation with or without internal fixation is an option when salvaging rare injuries like open grade III “floating ankle” injuries. Salvaged patients do suffer a cocktail of crippling disease characterized by psycho-socio-economic and physical disability and result in increased hospital costs. We recommend more prospective studies with long-term follow-up of such complex injuries to identify the indications for salvage and also the criteria for a successful salvage.     

Synthesis and biological evaluation of fluorescent leishmanicidal analogues of hexadecylphosphocholine (miltefosine) as probes of antiparasite mechanisms

The leishmanicidal mechanism of miltefosine (hexadecylphosphocholine, MT) is not clearly understood. Valuable insights into its mode of action could be obtained by fluorescence techniques, given suitably emitting analogues. In this regard, the synthesis and biological characterization of two fully competent MT fluorescent analogues is reported here: all-(E)-13-phenyltrideca-6,8,10,12-tetraenylphosphocholine (PTE-MT) and all-(E)-13-phenyltrideca-8,10,12-trien-6-ynylphosphocholine (PTRI-MT). Both compounds show large absorption coefficients and a modest, but usable, fluorescence yield. Their activities were very similar to that of MT and were recognized by the MT uptake system of Leishmania. Their localization in living L. donovani promastigotes by confocal microscopy show a homogeneous intracellular distribution of the fluorescence. The concentration of PTRI-MT within the parasites (ca. 1.7 mM) showed a 100-fold enrichment relative to its external concentration. These results are consistent with a multiple target leishmanicidal mechanism for MT and validate the application of these analogues for pharmacokinetic and diagnostic studies concerning the chemotherapy of leishmaniasis.     

Fungus-elicited metabolites from plants as an enriched source for new leishmanicidal agents: antifungal phenyl-phenalenone phytoalexins from the banana plant (Musa acuminata) target mitochondria of Leishmania donovani promastigotes

Two antifungal phenyl-phenalenone phytoalexins isolated from the banana plant (Musa acuminata) elicited with the fungus Fusarium oxysporum, together with a methoxy derivative of one of them and two epoxide precursors of their chemical synthesis, were tested for leishmanicidal activity on Leishmania donovani promastigotes and L. infantum amastigotes. Drugs inhibited proliferation of both forms of the parasite with a 50% lethal concentration range between 10.3 and 68.7 micro g/ml. Their lethal mechanism was found linked to the respiratory chain by a systematic approach, including electron microscopy, measurement of the oxygen consumption rate on digitonin-permeabilized promastigotes, and enzymatic assays on a mitochondrial enriched fraction. Whereas the whole set of compounds inhibited the activity of fumarate reductase in the mitochondrial fraction (50% effective concentration [EC(50)] between 33.3 and 78.8 micro g/ml) and on purified enzyme (EC(50) = 53.3 to 115 micro g/ml), inhibition for succinate dehydrogenase was only observed for the two phytoalexins with the highest leishmanicidal activity: anigorufone and its natural analogue 2-methoxy-9-phenyl-phenalen-1-one (EC(50) = 33.5 and 59.6 micro g/ml, respectively). These results provided a new structural motif, phenyl-phenalenone, as a new lead for leishmanicidal activity, and support the use of plant extracts enriched in antifungal phytoalexins, synthesized under fungal challenge, as a more rational and effective strategy to screen for new plant leishmanicidal drugs.