Mechanical properties of animal ligaments: a review and comparative study for the identification of the most suitable human ligament surrogates.

The interest in the properties of animal soft tissues is often related to the desire to find an animal model to replace human counterparts due to the unsteady availability of human tissues for experimental purposes. Once the most appropriate animal model is identified, it is possible to carry out ex-vivo and in-vivo studies for the repair of ligamentous tissues and performance testing of replacement and support healing devices. This work aims to present a systematic review of the mechanical properties of ligaments reported in the scientific literature by considering different anatomical regions in humans and several animal species. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. Moreover, considering the lack of a standard protocol for preconditioning of tissues, this aspect is also addressed. Ninety-six studies were selected for the systematic review and analysed. The mechanical properties of different animal species are reported and summarised in tables. Only results from studies reporting the strain rate parameter were considered for comparison with human ligaments, as they were deemed more reliable. Elastic modulus, ultimate tensile stress, and ultimate strain properties are graphically reported identifying the range of values for each animal species and to facilitate comparison between values reported in the scientific literature in animal and human ligaments. Useful similarities between the mechanical properties of swine, cow, and rat and human ligaments have been found.

Survival in HIV-infected patients with lymphoma according to the choice of antiretroviral treatment: an observational multicentre study.

OBJECTIVES: Lymphoproliferative disorders are often observed in HIV-positive patients. Combination antiretroviral treatment (cART) during antineoplastic chemotherapy is beneficial, but little is known about the clinical outcome according to different antiretroviral combinations. The aim of the study was to address this gap in current knowledge. METHODS: A retrospective study was conducted in five large Italian centres for the period from 1998 to 2015; HIV-positive patients diagnosed with lymphoma were included and demographic, clinical and therapeutic variables were recorded and associated with clinical outcomes. Bivariate and multivariate analyses were performed, including Cox proportional hazard models for survival. RESULTS: A total of 399 patients were included in the study. The most common types of lymphoma were diffuse large B-cell lymphoma (DLCLB; n = 164), Hodgkin lymphoma (HL; n = 99) and Burkitt lymphoma (BL; n = 57), followed by plasmablastic lymphoma (PBL; n = 38), T-cell lymphoma (TCL; n = 17), indolent lymphoma (n = 10) and other less common types (n = 14). cART was given to 327 (out of 387 evaluable) patients: in 216 subjects it was protease inhibitor (PI)-based, in 73 it was nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and in 18 it was integrase strand transfer inhibitor (INSTI)-based (the remaining 20 individuals received other regimens). The 5-year overall survival was 57.5% (52.8% for DLCLB, 67.8% for HL, 42.3% for BL, 60.6% for PBL and 64.7% for TCL). PI-based ART compared with other compounds was associated with worse survival in non-Hodgkin lymphoma (NHL) and HL patients combined (P ≤ 0.001) and in NHL patients alone (P < 0.001); grade 3-4 haematological toxicities were more commonly observed in PI-treated individuals. Lymphoma diagnosis in recent years, better immunovirological status, lower lymphoma stage and better prognostic indexes were associated with better survival. CONCLUSIONS: PI-based cART while on chemotherapy was associated with worse overall survival and more frequent haematological complications in HIV-positive patients with lymphoma.

HIV treatment and care among Italian inmates: a one-month point survey.

BACKGROUND: HIV infection, with an estimated prevalence be between 2 and 50 times those of the general adult population is a major health challenge for prison authorities worldwide. Since no nationwide surveillance system is present in Italy, data on HIV prevalence and treatment in prisons are limited to only a few and small observational studies. We aimed to estimate HIV prevalence and obtain an overview on diagnostic and therapeutic activities concerning HIV infection in the Italian penitentiary system. METHODS: We piloted a multi-centre cross-sectional study investigating the prevalence of HIV infection and assessing HIV-related medical activities in Italian correctional institutions. RESULTS: A total of 15,675 prisoners from 25 institutions, accounting for approximately one-fourth of the prison inmates in Italy, were included in the study, of whom, 97.7 % were males, 37.1 % foreigners and 27 % had a history of intravenous drug addiction. HIV-tests were available in 42.3 % of the total population, with a known HIV Infection proportion of 5.1 %. In the month prior to the study, 604 of the 1,764 subjects who entered prison were tested for HIV, with a HIV-positive prevalence of 3.3 %. Among the 338 HIV-positive prisoners, 81.4 % were under antiretroviral treatment and 73.5 % showed undetectable HIV-RNA. In 23/338 (6.8 %) a coinfection with HBV and in 189/338 (55.9 %) with HCV was also present. Among the 67 (19.8 %) inmates with HIV who did not receive HIV treatment, 13 (19.5 %) had T-CD4+ count <350 cells/mm(3) and 9 (69.2 %) of these had refused the treatment. The majority of the inmates with HIV-infection were on a PI-based (62.5 %) or on NNRTIs-based (24.4 %) regimen. Only a minority of patients received once daily regimens (17.2 %). CONCLUSIONS: Although clinical and therapeutic management of HIV infection remains difficult in Italian prisons, diagnostics, treatment and care were offered to the majority of HIV-infected inmates. Specific programs should be directed towards the prison population and strict cooperation between prison and health institutions is needed to increase HIV treatment.

P. aeruginosa bloodstream infections among hematological patients: an old or new question?

Pseudomonas aeruginosa is a well-known cause of severe and potentially life-threatening infections among hematological patients. A prospective epidemiological surveillance program ongoing at our Hematology Unit revealed an increase over time of P. aeruginosa bloodstream infections (BSI). Their impact on outcome and antibiotic susceptibility was analyzed. BSI which consecutively occurred at our institution during a 70-month period were evaluated and correlated with type of pathogen, status of underlying disease, neutropenia, previous antibiotic therapy, resistance to antibiotics, and outcome. During the observation period, 441 BSI were recorded. Frequency of Gram-negative BSI was higher than that of other pathogens (57.3%). Overall, 66 P. aeruginosa BSI were recorded; 22 out of 66 were multiresistant (MR P. aeruginosa). Thirty-day mortality for all BSI was 11.3%; it was 27.3% for P. aeruginosa BSI and 36.4% for MR P. aeruginosa. At multivariate analysis, only active hematological disease and P. aeruginosa BSI were associated to an increased risk of death. For MR P. aeruginosa, BSI mortality was 83.3% vs. 18.8% when empiric therapy included or not an antibiotic with in vitro activity against P. aeruginosa (p=0.011). Together with active disease, the emergence of P. aeruginosa BSI, particularly if multiresistant, was responsible for an increased risk of death among hematological patients at our institution. In this scenario, reconsidering the type of combination antibiotic therapy to be used as empiric treatment of neutropenic fever was worthwhile.

Epidemiological and clinical characteristics and behaviours of individuals with newly diagnosed HIV infection: a multicentre study in north Italy.

INTRODUCTION: We aimed to investigate socio-demographic, clinical and epidemiological characteristics and behaviours of subjects with new HIV diagnosis. METHODS: We carried out a multi-centre cross-sectional study comprising 17 infectious diseases units in the Lombardy Region, North Italy. All subjects with a first positive test for HIV infection examined in 2008-09 were interviewed using a structured questionnaire. RESULTS: 472 patients were enrolled (mean age 39.8 years, standard deviation [SD] 11.5), mostly males (78%), and born in Italy (77%). The most common routes of HIV transmission were heterosexual intercourse (49%) and sex among men who have sex with men (MSM) (40%). Never/sometimes use of a condom with occasional partners was associated with male gender, heterosexual transmission route, and with >10 sexual partners in their lifetime. 47% had previous HIV negative tests. Having had more than 2 previous HIV negative tests was associated with younger age, MSM transmission route, CD4+ lymphocyte count >350/microl and self-perception of risk. DISCUSSION: This study shows that there is a large portion of the adult population, especially heterosexual men aged 45 years and over, who are at high risk of acquiring and transmitting HIV infection and undergoing the HIV diagnostic test late, due to risk behaviours combined with a low perception of being at risk. Compared to people infected by heterosexual contacts, MSM show a greater awareness of being at risk of infection, but this knowledge has a low impact in reducing at-risk behaviours.

Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: results of a prospective study on 823 patients at a single institution.

BACKGROUND: Regular monitoring of bacterial epidemiology allows evaluation of antibacterial strategies adopted. The aim of this study was to disclose evolving trends in the epidemiology of infections and emerging antibiotic resistance in unselected inpatients with haematological cancers. METHODS: Febrile/infectious episodes occurring in 823 patients consecutively admitted to a single institution during a 16 month period were analysed. Levofloxacin prophylaxis was used in patients with >7 days expected neutropenia. RESULTS: Fever developed in 364 patients (44.2%) and an infection was documented in 187 (22.7%), either clinically (6.1%) or microbiologically (16.6%). Levofloxacin prophylaxis, used in 39.4% of cases, caused a reduction in febrile episodes only among neutropenic patients and no difference in the frequency of documented infections. Among 164 pathogens isolated, gram-negative (49.4%) outweighed gram-positive bacteria (40.9%), Escherichia coli being most frequent (23.2%). Fluoroquinolone resistance and methicillin resistance were the most frequent types of antibiotic resistance, occurring in 56.1% of bacterial isolates and in 66.7% of staphylococci, respectively. Fluoroquinolone-resistant E. coli accounted for 20.1% of all isolates and for 86.8% of E. coli. Multivariate analysis of risk factors for fluoroquinolone resistance identified prophylaxis (P < 0.001) and neutropenia >7 days (P = 0.02) as independent. Methicillin resistance was independently associated with prophylaxis (P = 0.041) and central venous catheters (P = 0.036). Infections by fluoroquinolone-resistant strains did not show a worse outcome. CONCLUSIONS: A shift towards gram-negative bacteria has been occurring in recent years in the bacterial epidemiology of haematological patients. Fluoroquinolone resistance is emerging as a major type of antibacterial resistance, particularly among E. coli strains. Further investigation is needed to explore the consequences of such epidemiological changes.

Risk factors for myocardial infarction in HIV-positive patients.

We describe the clinical characteristics of 12 HIV-infected patients who suffered from myocardial infarction (MI) in our clinical cohort. They were compared with a control group matched (1:2) for factors related to cardiovascular risk (age, gender, smoking habit, risk factor for HIV acquisition, hypertension, family history for relevant cardiovascular events, and body mass index) by conditional (fixed-effect) logistic regression analysis. Among patients with MI, 6/12 had never used protease inhibitors (PIs) or were antiretroviral therapy naive. The only variables marginally associated with MI were nadir CD4+ T-cell count <50/mm(3) (odds ratio (OR): 7.2; 95% confidence interval (CI) 0.81-64.2; P: 0.077) and zenith >100,000 HIV RNA copies/mL (OR: 7; 95% CI 0.81-60.2; P: 0.076) at univariate analysis. Moreover, the use of PIs did not result in being associated with the risk of MI. Our data show that in HIV-infected patients, PI use does not seem to have any negative impact on MI while the possible impact of advanced HIV infection itself needs further investigations.

HIV-1 genotype resistance pattern and evolution in patients failing nelfinavir-containing regimens.

Clinical and in vitro studies have suggested that nelfinavir (NFV)-containing regimens may not preclude the use of other protease inhibitors (PIs) in treatment sequencing. We have studied the prevalence of 30N mutation in a human immunodeficiency virus-1 (HIV-1)-infected cohort and the virological response to a PI-containing regimen in patients who had previously failed NFV. A total of 335 patients were included in the study; 32 of them were antiretroviral-naive and 303 were antiretroviral-experienced (251 were PI-experienced). Mutations 30N and/or 90M were not detected in sequences obtained either from the antiretroviral naive or non-PI-experienced patients. The 30N mutation was detected in 21/251 (8.3%) of PI-experienced patients and 90M in 103/251 (41%). Moreover, we have observed that the 88D and 77I mutations were present in more than 75% of patients harbouring the 30N HIV-1 variant and the 71T mutation was present in almost 50% of them. Finally, mutations 30N+90M were never detected together in the same HIV-1 strain. The 30N and 90M mutations were not observed together. The presence of mutations at positions 36, 46, 71, 77, and/or 88 in a 30N background, increases the risk of the cross-resistance to other PIs. The use of NFV as a first-line PI, as an application of drug sequencing strategies, may help preserve future PI options.

Oral cavity lymphomas in immunocompetent and human immunodeficiency virus infected patients.

Oral cavity lymphoma (OCL) seems to occur more frequently in HIV-positive patients, but it is presently unknown whether HIV-related immune deficit plays a role in modifying the prevalence and the characteristics of these lymphomas. To clarify this issue, we compared OCL occurring in immunocompetent and HIV-positive patients. A comparison was made between cases of OCL occurring among 543 and 123 NHL consecutively diagnosed at a single center in immunocompetent and HIV-positive patients respectively. The prevalence of oral cavity involvement at diagnosis was significantly lower in the immunocompetent subgroup (HIV-negative: 1.66%; HIV-positive: 7.3%, P = 0.002). Extranodal T/NK nasal-nasal-type lymphoma (ET/NK-NL) was observed in 3 of 9 immunocompetent patients, whereas plasmablastic lymphoma (PBL) was observed in 3 of 9 HIV-positive patients. EBV expression correlated with HIV-positivity. Response to treatment was similar between the two subgroups, but the overall prognosis was significantly worse among HIV-positive patients. Median survival was 34 months in immunocompetent vs. 9 months in HIV-positive patients (P < 0.01). A higher frequency of oral cavity lymphoma was associated with HIV infection. ET/NK-NL and PBL seemed to be clinical entities characteristically related to immunocompetent and HIV-positive subgroups, respectively. Chemotherapy was feasible and effective in both subgroups, although a poor prognosis was associated with immunodeficiency.

HIV-associated asymmetric lipodystrophy syndrome / HIV-associated asymmetric lipodystrophy syndrome

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Synchrotron radiation microtomography of bone engineered from bone marrow stromal cells.

Osteoprogenitor cells expanded in vitro and associated with porous ceramic scaffolds have been proposed as bone substitutes. Animal models have been developed to test the efficacy of various cell populations and scaffolds in promoting bone repair. Qualitative analysis of the new bone formed within the ceramic scaffold is relatively easy by conventional histology. On the other hand, quantitative data are difficult to obtain. X-ray computed microtomography was used as a possible experimental technique to obtain quantitative data on the three-dimensional structure of newly formed bone and of remaining scaffold in implants after 8 weeks in vivo. Measurements were performed at the European Synchrotron Radiation Facility on beamline ID19 with a spatial resolution of about 5 microm. This study clearly indicates the possibility of nondestructive quantitative analysis of bone-engineered constructs. The technique appears suitable to compare different scaffolds (and possibly different cell populations) with regard to bone formation efficiency and reabsorbability of biomaterials in the immunodeficient mouse model.

A case of oncogenic osteomalacia detected by 111In-pentetreotide total body scan.

A case of tumor-induced osteomalacia in a 35-year-old woman suffering from severe bone pain and muscle weakness is described. This uncommon disease is characterized by a reduced serum phosphorus level with elevated urinary phosphate excretion, normocalcemia, high serum bone alkaline phosphatase and a deficiency of 1,25 dihydroxyvitamin D3. The tumors responsible for oncogenic osteomalacia are usually small, benign and commonly located in bone or soft tissues of the head and the limbs, so the diagnosis can often be difficult. In this case a 111In-pentetreotide scintigraphy was able to detect a hemangiopericytoma located in the right mascellar sinus. Removal of the tumor resulted in the reversal of clinical and biochemical abnormalities.

HIV/HTLV co-infection: frequency and epidemiological characteristics among patients admitted to an Italian hospital.

BACKGROUND: Human T-cell leukemia/lymphoma viruses (HTLV) and HIV share identical modes of transmission and co-infections may be detected in populations that are highly exposed to common risk factors. MATERIALS AND METHODS: A total of 599 serum samples from HIV-positive patients attending our outpatient clinic during the last semester of 2000 were tested to assess the prevalence of HTLV co-infection in both Italian (n = 472) and non-European HIV-infected patients (n = 127). RESULTS: 72 samples were positive for HTLV-II. Most of the HTLV-II-positive patients were Italian (71/72, 98.6%) and 98.5% of them had acquired the HIV infection through use of intravenous recreational drugs. CONCLUSION: These data demonstrate a high HTLV-II exposure among HIV-positive intravenous drug users in our area which was not previously considered to be an area of endemicity for HTLV-II.

Lipodistrofia periférica / Peripheral lipodistrophy

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Hodgkin disease developing in patients infected by human immunodeficiency virus results in clinical features and a prognosis similar to those in patients with human immunodeficiency virus-related non-Hodgkin lymphoma.

BACKGROUND: Unlike aggressive non-Hodgkin lymphoma (NHL), Hodgkin disease (HD) develops rarely in patients who are infected by human immunodeficiency virus (HIV), and its characteristics are not well defined. The authors analyzed the clinicopathologic and prognostic features from a consecutive series of patients with HIV-associated HD who were observed at their institution and compared them with the features observed in a concurrent series of patients with systemic HIV-related NHL. METHODS: Eighteen patients with HIV infection who were diagnosed and treated uniformly from 1985 to 1999 at a single primary referral center were analyzed. Their demographic, immunologic, and clinicopathologic features; responses to treatment; and outcomes were compared with those of 98 patients with systemic NHL of aggressive histology who were diagnosed during the same period and with 165 HIV negative patients with HD. RESULTS: HIV-associated HD and NHL occurred in patients with similar age, gender, HIV risk factors, degree of immunodeficiency, and incidence of previous acquired immunodeficiency syndrome. The clinical presentation of HIV-associated HD was atypical and was more aggressive than in HIV negative patients (mediastinal involvement, 11%; Stage III-IV, 84%; B symptoms, 83%). It was similar to HIV-related NHL, except for the frequency of extralymph node disease, which was seen less frequently in patients who had HD (56%) compared with patients who had NHL (82%; P = 0.025), and the frequency of bone marrow involvement, which was unexpectedly higher in patients who had HD (50%) compared with patients who had NHL (20%; P = 0.011). Potentially curative treatment was administered to 77% of patients with HD and 66% of patients with NHL. Complete remission and disease recurrence rates as well as disease free and overall survival rates did not differ significantly, with estimated overall survival at 5 years of 24% in patients with HD and 23% in patients with NHL. CONCLUSIONS: HIV-associated HD is an aggressive disease with demographic, clinical, and prognostic features nearly identical to those of HIV-related NHL.