Pulmonary tuberculosis followed by sarcoidosis in an HIV-infected patient: a case report and a simplified diagnostic flowchart for diagnosis and treatment of sarcoidosis

The diagnosis of sarcoidosis in a patient living with HIV infection is an uncommon event and a challenge for clinicians. Clinical manifestations are variable and fluctuating depending to adherence to ARV therapy and to the level of CD4 count. We analyze here one chronic case in which sarcoidosis appeared clinically two years after pulmonary tuberculosis. The course of the disease was influenced and prolonged by frequent interruptions of antiretroviral therapy. Moreover the diagnosis and the decision to treat have been delayed by the need of exclusion of other pathologies, principally tuberculosis reactivation/reinfection, other mycobacterial diseases, hematologic malignancies. We propose a simplified flowchart for diagnosis and follow up of sarcoidosis, which may also be applied to patients with HIV infection. Diagnosis of latent tuberculosis infection (LTBI) may be difficult in these patients, because the immunological paradox of sarcoidosis. For this reason, following exclusion of active tuberculosis, we advise to submit all sarcoidosis patients to IPT (isoniazid preventive therapy), when immunosuppressive therapy is started

Osteonecrosis of the jaw after long-term oral bisphosphonates, followed by short-term denosumab treatment for osteoporosis: a case report

Bisphosphonates and denosumab are antiresoptive agents and are mainly used for management of metastatic bone cancer, osteoporosis and other diseases. Bisphosphonates (BP) can reduce skeletal related events (SRE) by 30–50%1; denosumab (D) has been found even more effective than BP2. BP and D have been both associated to osteonecrosis of the jaw (ONJ). We report a case of an osteoporotic woman (62 yrs), complaining maxillary intense pain after a recent tooth molar extraction, observed in July 2013 at our centre. She mentioned previous treatments with monthly ibandronate (Bonviva ® 150 mg) per os (from January 2003 to April 2010), risedronate (35 mg weekly, from May 2010 to May 2012) and two administrations (in August 2012 and in January 2013) of denosumab (Prolia ®, 60 mg sc every 6 months). Of note, she also reported a previous incisor extraction that was performed in July 2012 (before denosumab) without ONJ onset. No further systemic or local risk factors were referred. Intraorally, bone exposure of right emimaxilla was present; osteolysis area was observed in in CT scans. According to Bedogni et al.3, the ONJ case was classified as stage II B. Medical therapy (ampicillin/sulbactam im 2 times/die, metronidazole per os 3 times/die, chlorhexidine 0.2% mouth rinses) was administered. One week later, the patient was asymptomatic but within the same stage (IIA); she was referred to Oral and Maxillofacial surgery for surgical management

L-PRF application in extraction sockets of bisphosphonate-treated patients: preliminary results

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe adverse event related to bisphosphonates (BPs) therapy; tooth extraction has been described as the main trigger. Autologous platelet concentrates, such Leukocyte-Platelet Rich Fibrin (L-PRF, Intraspin !) are designed to release platelet growth factors, improving the tissue healing in oral surgery. The aim of this study was to evaluate the efficacy and safety of our dental extraction protocol applied in BPs patients

JCV-specific T-cells producing IFN-gamma are differently associated with PmL occurrence in HIV patients and liver transplant recipients

Aim of this work was to investigate a possible correlation between the frequency of JCV-specific T-cells and PML occurrence in HIV-infected subjects and in liver transplant recipients. A significant decrease of JCV-specific T-cells was observed in HIV-PML subjects, highlighting a close relation between JCV-specific T-cell immune impairment and PML occurrence in HIV-subjects. Interestingly, liver-transplant recipients (LTR) showed a low frequency of JCV-specific T-cells, similar to HIV-PML subjects. Nevertheless, none of the enrolled LTR developed PML, suggesting the existence of different immunological mechanisms involved in the maintenance of a protective immune response in LT

GPS Digital Nudge to Limit Road Crashes in Non-Expert Drivers

Many automotive industries are developing technologies to assist human drivers in sug-gesting wiser choices to improve drivers’ behaviour. The technology that makes use of this modality is defined as a “digital nudge”. An example of a digital nudge is the GPS that is installed on smart-phones. Some studies have demonstrated that the use of GPS negatively affects environmental learning because of the transformation of some spatial skills. The main purpose of this study was to investigate the use of the GPS nudge and its relationship with spatial ability, together with its function in supporting the driving behaviour of non-expert drivers, in order to reduce the number of road crashes. A total of 88 non-expert drivers (M age = 21 years) filled in questionnaires and carried out tasks to measure spatial abilities, sense of direction, driver behaviour, and six different real-life driving scenarios. The results reveal that the higher the spatial skills are, the greater the GPS use is, and that drivers who use GPS improve their sense of direction. Moreover, people with high visuospatial abilities use GPS more extensively. Finally, young drivers do not consider the GPS aid to be useful when they have no time pressure. The results are discussed by taking into account the familiarity-and-spatial-ability model

Clinical and functional outcomes of the PCCP study : a multi-center prospective study in Italy

The standard surgical management of hip fractures is associated with tissue trauma and bleeding which are added to the fracture injury. The percutaneous compression plate (PCCP) is a minimally invasive device that has been demonstrated in previous studies to reduce postoperative complications and blood loss. This prospective, multi-center, observational study assessed clinical and functional outcomes with PCCP as treatment for trochanteric fractures. Patients with a stable or unstable proximal femoral fracture of type AO 31.A1 or 31.A2 were enrolled in eight hospitals in Italy. The primary outcome of interest was the recovery of the pre-fracture functional status at 1-year follow-up; secondary outcomes of interest included blood transfusions, surgical time, complications, and mortality. A total of 273 patients were enrolled. The ASA score was 3 or 4 in 72.5 % of patients. The mean surgical time was 44.1 min; the mean post-surgery blood transfusions was 0.9 units. At 1 year, 48 patients (17.6 %) died, 28 (10.2 %) were lost to follow-up, 4 patients (1.5 %) were excluded, hence 193 patients (70.3 %) were available for final evaluation. At the 1-year follow-up visit, 51.9 % of patients recovered or improved their pre-fracture modified Harris Hip Score, 49.1 % of patients improved or maintained their walking abilities, and 66.6 % of patients residing at home pre-surgery maintained their domicile. The overall mortality rate was 17.6 %. Major complications included two fracture collapses, one excessive sliding of the cephalic screw leading to a partial fracture collapse and one back-out of the diaphyseal screw. This study demonstrates that treatment of trochanteric fractures with PCCP gives good outcomes and significant advantages such as low blood loss, short surgical time, low risk of complications, and good functional recovery in the majority of the patients

Which executive functioning deficits are associated with AD/HD, ODD/CD and comorbid AD/HD+ODD/CD?

Item does not contain fulltextThis study investigated (1) whether attention deficit/hyperactivity disorder (AD/HD) is associated with executive functioning (EF) deficits while controlling for oppositional defiant disorder/conduct disorder (ODD/CD), (2) whether ODD/CD is associated with EF deficits while controlling for AD/HD, and (3)~whether a combination of AD/HD and ODD/CD is associated with EF deficits (and the possibility that there is no association between EF deficits and AD/HD or ODD/CD in isolation). Subjects were 99~children ages 6–12 years. Three putative domains of EF were investigated using well-validated tests: verbal fluency, working memory, and planning. Independent of ODD/CD, AD/HD was associated with deficits in planning and working memory, but not in verbal fluency. Only teacher rated AD/HD, but not parent rated AD/HD, significantly contributed to the prediction of EF task performance. No EF deficits were associated with ODD/CD. The presence of comorbid AD/HD accounts for the EF deficits in children with comorbid AD/HD+ODD/CD. These results suggest that EF deficits are unique to AD/HD and support the model proposed by R. A. Barkley (1997).17 p

Virological Response in Cerebrospinal Fluid to Antiretroviral Therapy in a Large Italian Cohort of HIV-Infected Patients with Neurological Disorders

The aim of the present study was to analyse the effect of antiretroviral (ARV) therapy and single antiretroviral drugs on cerebrospinal fluid (CSF) HIV-RNA burden in HIV-infected patients affected by neurological disorders enrolled in a multicentric Italian cohort. ARVs were considered "neuroactive" from literature reports. Three hundred sixty-three HIV-positive patients with available data from paired plasma and CSF samples, were selected. One hundred twenty patients (33.1%) were taking ARVs at diagnosis of neurological disorder. Mean CSF HIV-RNA was significantly higher in na\uefve than in experienced patients, and in patients not taking ARV than in those on ARV. A linear correlation between CSF HIV-RNA levels and number of neuroactive drugs included in the regimen was also found (r = -0.44, P < 0.001). Low -plasma HIV-RNA and the lack of neurocognitive impairment resulted in independently associated to undetectable HIV-RNA. Taking nevirapine or efavirenz, or regimen including NNRTI, NNRTI plus PI or boosted PI, was independently associated to an increased probability to have undetectable HIV-RNA in CSF. The inclusion of two or three neuroactive drugs in the ARV regimen was independently associated to undetectable viral load in CSF. Our data could be helpful in identifying ARV regimens able to better control HIV replication in the CNS sanctuary, and could be a historical reference for further analyses

INPP4B overexpression and c-KIT downregulation in human achalasia.

BACKGROUND: Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia. METHODS: Esophageal full-thickness biopsies from 42 (22 females; age range: 16-82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the "edgeR" option of R-Bioconductor. Data were validated by real-time RT-PCR, western blotting and immunohistochemistry. KEY RESULTS: Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P 64 10-3 . Nine genes with a P 64 10-4 were further validated. CYR61, CTGF, c-KIT, DUSP5, EGR1 were downregulated, whereas AKAP6 and INPP4B were upregulated in patients vs controls. Compared to controls, immunohistochemical analysis revealed a clear increase in INPP4B, whereas c-KIT immunolabeling resulted downregulated. As INPP4B regulates Akt pathway, we used western blot to show that phospho-Akt was significantly reduced in achalasia patients vs controls. CONCLUSIONS &amp; INFERENCES: The identification of altered gene expression, including INPP4B, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC changes underlying primary achalasia