Differential tissue distribution of discrete typing units after drug combination therapy in experimental Trypanosoma cruzi mixed infection.

The aim of the present work was to evaluate the distribution of the different clones of the parasite prevailing after treatment with benznidazole (BZ) and clomipramine (CLO), in mice infected with Trypanosoma cruzi, Casibla isolate which consists of a mixture of two discrete typing units (DTUs). Albino Swiss mice were infected and treated with high and low concentrations of BZ (100 or 6.25 mg/kg), CLO (5 or 1.25 mg/kg), or the combination of both low doses (BZ6.25 + CLO1.25), during the acute phase of experimental infection. Treatment efficacy was evaluated by comparing parasitaemia, survival and tissular parasite presence. For DTUs genotyping, blood, skeletal and cardiac muscle samples were analysed by multiplex quantitative polymerase chain reaction. The combined treatment had similar outcomes to BZ6.25; BZ100 was the most effective treatment, but it failed to reach parasite clearance and produced greater histological alterations. Non-treated mice and the ones treated with monotherapies showed both DTUs while BZ6.25 + CLO1.25 treated mice showed only TcVI parasites in all the tissues studied. These findings suggest that the treatment may modify the distribution of infecting DTUs in host tissues. Coinfection with T. cruzi clones belonging to different DTUs reveals a complex scenario for the treatment of Chagas disease and search for new therapies.

The adductor tubercle as an important landmark to determine the joint line level in total knee arthroplasty: from radiographs to surgical theatre.

PURPOSE: The restoration of the normal joint line (JL) is important both in primary and revision total knee arthroplasty (TKA). However, the assessment of the femoro-tibial JL is still controversial. A strong correlation between femoral width (FW) and distance from adductor tubercle (AT) to JL was found on radiographs, with a ratio of 0.54. The hypothesis was that this ratio was applicable also in the surgical theatre by using measurements obtained intra-operatively with a caliper. METHODS: Femoral width, AT to JL distance and the RATIO between AT to JL distance and FW of 40 patients who underwent TKA were measured on radiograph and intra-operatively. Bland-Altman agreement tests with repeated measurements and linear regression analysis were used. The ratio was used to estimate the distance between JL and AT. RESULTS: The AT to JL distance/FW ratio calculated with linear regression resulted 0.54 for radiographic measurements and 0.53 for intra-operative measurements. There was no difference (0.009 ± 0.03) between the calculated ratios on radiographic and intra-operative measurements, and the correlation between intra-operative and radiographic measurements was 0.5 (p = 0.0016). CONCLUSIONS: This study shows that the validity of the radiographic method which uses an AT to JL distance/FW ratio to determine the level of the JL is confirmed also when using intra-operatively acquired measurements. Thus, this ratio represents a reliable tool to determine the JL level even in challenging prosthetic revision cases when the anatomical JL is missing. LEVEL OF EVIDENCE: Case series, Level IV.

Küntscher nails with static cement spacer: A simple technique in periprosthetic knee infections with massive bone loss and instability.

BACKGROUND: Two-stage revision for periprosthetic knee infection is challenging in cases of massive bone loss and instability. The present study aims to describe our experience with an alternative technique of reinforced cement spacer, usually necessary in these situations, focusing on its advantages and clinical results. METHODS: We retrospectively identified all patients who underwent a two-stage revision for periprosthetic knee infection using two intramedullary Küntscher nails as reinforcement from January 2010 to September 2018. From each medical record, we extracted the type of explanted prosthesis, isolated micro-organism, number of cement spacers before index procedure (and related episodes of spacer dislocation) and final treatment. RESULTS: Twelve patients were identified, mean age of 64.0 years (range 39-85). In four of them, the reinforced spacer was used twice for persistent infection, with a total of 16 procedures performed and no cases of dislocation. Ten patients were finally treated with reimplantation or arthrodesis with intramedullary nails, whereas an above-knee amputation was necessary for two patients. Infection was eradicated in 10 patients out of 12 (83%) at a mean follow up of 34.3 months (range 10-62). CONCLUSIONS: This technique is an effective alternative to traditional spacers in cases of massive bone loss, producing a mechanically stable joint and preserving adequate tissue tensions. The construct is technically easy to perform and, not less importantly, to remove during stage 2. Further studies, with larger groups, are necessary to determine its validity.

Efficacy of an alpha-hydroxy acid (AHA)-based cream, even in monotherapy, in patients with mild-moderate acne.

AIM AND METHODS: The treatment of mild-moderate acne with topical drugs in association with appropriate cosmetics is currently the golden standard. The tolerability and efficacy of a cream formulated with a new mix of alpha-hydroxy acids (Hyseac AHA cream) in 248 patients with mild-moderate acne (comedonic, inflammatory, or mixed) have been investigated in a multicenter, non-randomized, open study by 10 dermatologists from different Italian areas during their routine practice. The medication with Hyseac AHA cream was prescribed at first consultation for 60 days, twice a day, either as a monotherapy (49.2% patients) or in association with a pharmacological treatment (50.2%). RESULTS: The tolerability was good to excellent in 92.3% patients, without significant differences between patients using AHA cream in monotherapy (90.0%) or associated with concomitant pharmacological treatment (97.6%). The efficacy was overall high in 64.2% patients, again without significant differences related to concomitant pharmacological treatment or not (64.8% vs. 63.3%) and/or the acne clinical type (comedonic vs. inflammatory vs. mixed: 69.2% vs. 66.7% vs. 58%). CONCLUSION: The results of this study, while confirming the high tolerability and efficacy of this AHA cream in the treatment of mild/moderate acne, reasonably suggest its possible use also in monotherapy. Furthermore, its use can be reasonably hypothesized as a maintenance treatment after specific pharmacological treatment even in more severe acne types.

Involvement of the beta-adrenergic system in the cardiac chronic form of experimental Trypanosoma cruzi infection.

Changes in the cardiac beta-adrenergic system in early stages of Trypanosoma cruzi infection have been described. Here, we studied an early (135 days post-infection-p.i.) and a late stage (365 days p.i.) of the cardiac chronic form of the experimental infection (Tulahuen or SGO-Z12 strains), determining plasma epinephrine and norepinephrine levels, beta-receptor density, affinity and function, cardiac cAMP concentration and phosphodiesterase activity, cardiac contractility, and the presence of beta-receptor autoantibodies. Tulahuen-infected mice presented lower epinephrine and norepinephrine levels; lower beta-receptor affinity and density; a diminished norepinephrine response and higher cAMP levels in the early stage, and a basal contractility similar to non-infected controls in the early and augmented in the late stage. The Tulahuen strain induced autoantibodies with weak beta-receptor interaction. SGO-Z12-infected mice presented lower norepinephrine levels and epinephrine levels that diminished with the evolution of the infection; lower beta-receptor affinity and an increased density; unchanged epinephrine and norepinephrine response in the early and a diminished response in the late stage; higher cAMP levels and unchanged basal contractility. The SGO-Z12 isolate induced beta-receptor autoantibodies with strong interaction with the beta-receptors. None of the antibodies, however, acted a as beta-receptor agonist. The present results demonstrate that this system is seriously compromised in the cardiac chronic stage of T. cruzi infection.

Prenatal diagnosis of androgen insensitivity syndrome.

Androgen insensitivity syndrome (AIS) (OMIM 300068) is an X-linked recessive genetic disorder with an XY karyotype that is caused by androgen receptor (AR) defects. We report a prenatal diagnosis case with clinical and molecular findings. The fetal phenotype was female, moreover the autopsy revealed the presence of abdominal testes confirmed by histopathological examination. The AR gene molecular analysis performed on the fetal DNA showed the presence of a c.2493C>T change in exon 4. The single nucleotide change resulted in a Q711X amino acid substitution within the AR ligand-binding domain of the protein that has never been described before in the literature. AIS is an important consideration in pregnancies that show sex discordance in ultrasonography and karyotype results with the opportunity to perform molecular analysis of the AR gene in order to confirm the diagnosis.

Treatment of life-threatening type I refractory coeliac disease with long-term infliximab.

Whereas medical approach to coeliac disease is well defined, treatment of patients who fail to respond to a gluten-free diet remains still problematic. We describe the case of a 68 years DQ-2 positive male who lost response to a strict gluten-free diet after an initial response over a 3-year period. His conditions became critical despite high dose prednisone treatment. After a careful differential diagnosis, the patient was classified as having a type I refractory coeliac disease and a single infusion of infliximab at 5mg/kg was given with excellent clinical results. However, clinical response was lost despite background therapy with azathioprine. Six months after the single infusion an induction therapy with infliximab and, thereafter, maintenance every 8 weeks was administered with excellent clinical results. Since small bowel histology recovered very slowly treatment was continued over the following 2 years with a return to near normal architecture. This case shows that anti-tumour necrosis factor treatment may be used in carefully selected patients with type I refractory coeliac disease.

ST/G ACL reconstruction: double strand plus extra-articular sling vs double bundle, randomized study at 3-year follow-up.

Several investigators have reported the presence of biomechanical, kinematic, anatomic, fiber orientation patterns and biological differences between the anteromedial bundle and the posterolateral bundle of ACL. The purpose of this prospective randomized study was to compare the clinical, instrumental and X-ray outcome of two ACL reconstruction techniques with hamstring tendons: one with a single intra-articular bundle associated to an extra-articular sling, the second with a more anatomic double-bundle technique that reproduces better the native ACL function. From an initial group of 100 patients who underwent ACL reconstruction, 72 patients (35 single bundle plus lateral plasty and 37 double bundle) were evaluated with IKDC, Tegner score, KT2000 arthrometer, Activity Rating Scale, Psychovitality Questionnaire and Ahlback radiographic score at a mean 3 years follow-up. Double-bundle group showed significantly better results regarding IKDC, ROM, Activity Rating Scale and time to return to sport. Also KT 2000 showed significant differences in objective stability. The double-bundle technique for ACL reconstruction described in this paper has demonstrated significantly better subjective, objective and functional results compared with a double-stranded hamstrings plus extra-articular sling at a minimum 3-year follow-up.

Trypanosoma cruzi: Cardiac mitochondrial alterations produced by different strains in the acute phase of the infection.

The parasite Trypanosoma cruzi is the causative agent of Chagas disease. T. cruzi invasion and replication in cardiomyocytes induce cellular injuries and cytotoxic reactions, with the production of inflammatory cytokines and nitric oxide, both source of reactive oxygen species. The myocyte response to oxidative stress involves the progression of cellular changes primarily targeting mitochondria. We studied the cardiac mitochondrial structure and the enzymatic activity of citrate synthase and respiratory chain CI-CIV complexes, in Albino Swiss mice infected with T. cruzi, Tulahuen strain and SGO Z12 isolate, in two periods of the acute infection. Changes in the mitochondrial structure were detected in both infected groups, reaching values of 71% for Tulahuen and 88% for SGO Z12 infected mice, 30 days post infection. The citrate synthase activity was different according to the evolution of the infection and the parasite strain, but the respiratory chain alterations were similar with either strain.

Percutaneous treatment of hallux valgus: What's the evidence? A systematic review.

Hallux and first MTP joint have a fundamental role in the transfer of the weight-bearing load during the normal ambulation. The aim of this paper is to review and analyze the available literature about the percutaneous surgical management of the hallux valgus to highlight its strengths and weakness, also comparing with other minimal invasive techniques. A systematic search of PubMed and Google Scholar databases has been performed, covering the period between 1981 and 2016. Various combinations of the keyword terms "PDO," "hallux valgus," "bunion," "percutaneous," "surgery," "non-invasive," "minimal invasive," "burr," "osteotomy," "distal," "linear," "saw" have been used.Four papers, published from 2005 to 2015, fulfilled the inclusion criteria. A total of 464 hallux valgus has been treated with a properly percutaneous distal first metatarsal osteotomy. Mean AOFAS score, retrieved from the 4 studies included in our review, has been recorded. There are different aspects that the foot and ankle non-experienced surgeon has to consider about percutaneous surgery: limitation of the tools, radioexposure, lack of direct visual control of the osteotomy and higher costs and patient risk due to surgical time.

Differential tissue distribution of Trypanosoma cruzi during acute experimental infection: Further evidence using natural isolates.

In the present work, we evaluated the effect of mixed Trypanosoma cruzi infections, studying the biological distribution of the different parasites in blood, heart and skeletal muscle during the acute phase. Albino Swiss mice were infected with different parasite strain/isolates or with a combination of them. The parasites in the different tissues were typified through specific PCR, population variability was analyzed through RFLP studies and parasitological and histopathological parameters were evaluated. We found a predominance of TcII and TcVI in all tissues samples respect to TcV and different parasite populations were found in circulation and in the tissues from the same host. These results verify the distribution of parasites in host tissues from early stages of infection and show biological interactions among different genotypes and populations of T. cruzi.

Concurrent femoral and tibial osteotomies versus soft tissue balance in total knee arthroplasty: A technical case report.

This case report outlines some of the challenges as well as limitations in correction of osteoarthritis of the knee in combination with extra-articular deformities,and provides a novel and straightforward surgical solution in overcoming these challenges. We describe the case of a 37-year-old male who suffered from advanced bilateral tri-compartmental knee arthritis due to untreated bloodstream-sourced osteomyelitis after birth. Radiographs and surgery confirmed extremely severe deformities. We performed two different surgical techniques in order to correct extra-articular deformities (one-stage approach of concurrent tibial and femoral osteotomy and total knee arthroplasty on one side, and soft tissue balancing with "pie-crusting technique" plus total knee arthroplasty on the other side), with description of subsequent results at 36-months follow-up.

Changes in the cardiac beta-adrenergic system provoked by different T. cruzi strains.

BACKGROUND: It has been demonstrated that the beta-adrenergic signal transduction system is altered somewhere along its pathway in Trypanosoma cruzi infected hearts and we think that these alterations would differ according to the infection phase and the parasite strain. Their study would be important for the understanding of the disease's pathophysiology. METHODS: In the present work we studied important components of this system in mice hearts infected with T. cruzi, Tulahuen strain and with SGO-Z12 isolate, obtained from a patient of an endemic area, in the acute phase of the infection, determining: the plasma catecholamines levels, the beta-receptors density and affinity as well as their function, the cardiac concentration of cAMP and the cardiac contractility as the physiologic response to the initial stimulus. RESULTS: Plasma catecholamines levels were diminished in both infected groups when compared to the uninfected one (P < 0.01). The receptor's affinity was also diminished (P < 0.05) while their density was augmented only in the SGO-Z12 infected one (P < 0.01). The cAMP levels were higher in both infected groups (P < 0.01), the basal contractile force however increased only in the Tulahuen infected one (P < 0.01) while the response to catecholamines remained unchanged. The hearts infected with the SGO Z12 isolate presented an inferior response to epinephrine (P < 0.05) than the ventricles infected with the Tulahuen strain. CONCLUSIONS: This model represents an important approach to understand the biochemical, physiological and molecular changes in the cardiac beta-adrenergic signalling that clearly begin in the acute phase of Chagas' disease and reveal a clear differentiation in the alterations produced by different parasite strains.

Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease.

Thioridazine (TDZ) is a phenothiazine that has been shown to be one of the most potent phenothiazines to inhibit trypanothione reductase irreversibly. Trypanothione reductase is an essential enzyme for the survival of Trypanosoma cruzi in the host. Here, we reviewed the use of this drug for the treatment of T. cruzi experimental infection. In our laboratory, we have studied the effect of TDZ for the treatment of mice infected with different strains of T. cruzi and treated in the acute or in the chronic phases of the experimental infection, using two different schedules: TDZ at a dose of 80 mg/kg/day, for 3 days starting 1h after infection (acute phase), or TDZ 80 mg/kg/day for 12 days starting 180 days post infection (d.p.i.) (chronic phase). In our experience, the treatment of infected mice, in the acute or in the chronic phases of the infection, with TDZ led to a large reduction in the mortality rates and in the cardiac histological and electrocardiographical abnormalities, and modified the natural evolution of the experimental infection. These analyses reinforce the importance of treatment in the chronic phase to decrease, retard or stop the evolution to chagasic myocardiopathy. Other evidence leading to the use of this drug as a potential chemotherapeutic agent for Chagas disease treatment is also revised.

Thioridazine treatment prevents cardiopathy in Trypanosoma cruzi infected mice.

Trypanosoma cruzi trypanothione reductase is an enzyme that has been identified as a potential target for chemotherapy. Thioridazine inhibits it and prevented cardiopathy in mice infected with T. cruzi Tulahuen strain. As not all T. cruzi strains respond to treatment in the same way, an isolate from a chronic patient (SGO Z12) was used; parasitaemias were studied along with, survival, serology, electrocardiography, histology and cardiac beta receptor function. Parasitaemia in thioridazine (80 mg/(kg day) for 3 days) treated mice was less and lasted for a shorter period (P < 0.01), there were reduced electrocardiographic and histological alterations and significantly improved survival (80% of non-treated died). Treated mice had lower receptor affinity and higher density as a compensatory mechanism, modifying the course of T. cruzi infection (SGO Z12 isolate) and preventing the consequent cardiopathy.

[Nipple discharge: indications for surgery]. / La mammella secernente: indicazioni alla chirurgia.

Nipple discharges are related to physiological events or due to benign lesions of the breast. Sometimes they can express mammary cancers. The authors report their experience of the diagnosis and treatment of 1241 patients with secreting breast. They underline the importance of a correct diagnostic protocol to select cases needing surgical treatment.

[Acquired phimosis due to lichen sclerosus et atrophicus]. / La fimosi acquisita da lichen sclero-atrofico.

From January 1986 to December 1991, 6 cases of acquired phimosis secondary to balanitis xerotica obliterans were observed. The authors report their experience in the diagnosis and treatment of this disease. Five patients were treated with plastic of the foreskin, one was circumcised and treated with local instillation of corticoids. The authors conclude that the histological study of the specimen is very important to demonstrate the nature of the lesion.

Chronic anti-platelet therapy: a contraindication for platelet-rich plasma intra-articular injections?

We report the case of a 50 years-old man who complained persisting knee pain that limited almost completely his sport performance. Since he previously underwent multiple aortocoronaric by-passes, he presented a chronic anti-aggregant therapy. In spite of this clinical history, he was still sport active and able to run long-distance races, until knee symptoms limited is activity level. Conservative treatment approaches proved to be unsuccessful, thus we decided to treat him by 3 Platelet-rich Plasma (PRP) injections even if chronic anti-aggregant therapy is generally regarded as a contra-indication for PRP, since this kind of drugs impairs platelet function and granules' release. Despite these premises, the clinical outcome was very satisfactory and the patient was able to rapidly resume intensive running activity. This experience opens new questions regarding the real potential of PRP in treating degenerative musculo-skeletal disorders, and in particular on its range of biological actions and on its limitations for clinical application.

Circulating Trypanosoma cruzi populations differ from those found in the tissues of the same host during acute experimental infection.

We evaluated the presence and distribution of two Trypanosoma cruzi natural isolates in blood, heart, skeletal muscle, liver, and spleen tissues in the acute phase of the experimental infection (35 days postinfection) in order to determine if the populations present in blood were different to those found in the tissues of the same host. Thirty mice were infected with 50 forms of each isolate or with a combination of them. Presence and molecular characterization of the parasites in the host tissues were determined by specific PCR. Cardiac and skeletal muscle alterations were analyzed by histological studies. T. cruzi variability in the host tissues was analyzed through RFLP studies. Both isolates used consisted of a mixture of two T. cruzi lineages. Specific PCRs were positive for most of the samples from the 3 groups analyzed. Cardiac and skeletal muscle sections from the groups infected with one isolate presented mild to moderate inflammatory infiltrates; the group infected with both isolates showed severe inflammatory infiltrates and the presence of amastigote nests in both tissues. Different parasite populations were found in circulation and in the tissues from the same host. These results are important for patients with high probability of mixed infections in endemic areas and contribute to the knowledge of parasite/host interactions.