Investigating coping and stigma in people living with HIV through narrative medicine in the Italian multicentre non-interventional study DIAMANTE.

Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients' coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping.

Salivary gland tissues and derived primary and metastatic neoplasms: unusual pitfalls in the work-up of sellar lesions. A systematic review.

PURPOSE: Salivary gland (SG) tissue and derived neoplasms may occur in the sellar region. As the current literature is mostly limited to case reports, the puzzling case of an inflammatory SG removed by transsphenoidal surgery (TS) and mimicking a prolactinoma prompted us to perform the first systematic review of these unusual conditions. METHODS: A systematic literature search was conducted according to the PRISMA guidelines. Forty-four individual cases-non-neoplastic enlarged salivary glands (NNESG, n = 15), primary benign (n = 7) and malignant (n = 8) ectopic salivary tumours (ST) and sellar metastasis from eutopic primary ST (n = 14)-were suitable for the analysis of clinical, radiological and pathological characteristics. Therapeutic outcome was reviewed as a secondary endpoint. RESULTS: All cases were diagnosed after surgery. NNESG commonly affected young and/or female patients, typically leading to headaches and hyperprolactinemia and originating close to the neurohypophysis. Submucosal SG should be excluded before concluding to an intrasellar NNESG after TS. No gender or age predominance was found for primary ectopic ST, which present as large tumors, with histological phenotypes similar to common ST. Hypopituitarism and diabetes insipidus were more frequent in ST than in NNESG. NNESG and benign ectopic ST rarely recur. Malignant ectopic ST should be distinguished from secondary localizations of eutopic ST reaching the sella by contiguity or metastatic spread; both share a frequent unfavorable outcome. CONCLUSION: Sellar neoplasms derived from SG are rare but misleading conditions and pituitary dysfunction is likely to be more common than currently reported. Appropriate pathological evaluation and multidisciplinary approach are required.

Resection of the irradiated esophagus: the impact of lymph node yield on survival.

There is debate surrounding the appropriate threshold for lymph node harvest during esophagectomy in patients with esophageal cancer, specifically for those receiving preoperative radiation. The purpose of this study was to determine the impact of lymph node yield on survival in patients receiving preoperative chemoradiation for esophageal cancer. The National Cancer Database (NCDB) was utilized to identify patients with esophageal cancer that received preoperative radiation. The cohort was divided into patients undergoing minimal (<9) or extensive (≥9) lymph node yield. Demographic, operative, and postoperative outcomes were compared between the groups. Kaplan-Meier analysis with the log rank test was used to compare survival between the yield groups. Cox proportional hazards model was used to determine the association between lymph node yield and survival. In total, 886 cases were included: 349 (39%) belonging to the minimal node group and 537 (61%) to the extensive group. Unadjusted 5-year survival was similar between the minimal and extensive groups, respectively (37.3% vs. 38.8%; P > 0.05). After adjustment using Cox regression, extensive lymph node yield was associated with survival (hazard ratio 0.80, confidence interval 0.66-0.98, P = 0.03). This study suggests that extensive lymph node yield is advantageous for patients with esophageal cancer undergoing esophagectomy following induction therapy. This most likely reflects improved diagnosis and staging with extensive yield.

Consecutive episodes of heart and kidney failure in an "otherwise" healthy young man.

BACKGROUND: Acute renal failure is a rare occurrence in a patient with an unremarkable past medical history and should always lead to an in depth clinical study. The occurrence in the same healthy young subject, of consecutive episodes of heart failure and of acute renal failure is an even rarer event and should prompt diagnostic tests and restrict the diagnostic hypotheses. CASE PRESENTATION: We present the case of a 28 year-old man who, while waiting to undergo assessment for a mild chronic kidney disease, was diagnosed with decompensated dilated cardiomyopathy and placed on diuretics and ß-blockers. After few weeks he developed a non oligoanuric acute renal failure with a slight elevation of serum calcium. Renal biopsy proved suggestive for renal sarcoidosis; thus the hypothesis of systemic sarcoidosis with cardiac and renal involvement was possible avoiding further delay in initiation of therapy. CONCLUSIONS: Cardiac sarcoidosis is usually silent but the majority of cases are diagnosed when cardiac symptoms are present in a patient with systemic sarcoidosis. Renal involvement with granulomatous interstitial nephritis is also quite rare and can be an unexpected finding at kidney biopsy. This case highlights the need to evaluate thoroughly clinical problems that do not fit in a specific scenario and emphasizes the importance of performing a kidney biopsy in case of kidney failure of unknown etiology.

Ferrous iron- and ammonium-rich diffuse vents support habitat-specific communities in a shallow hydrothermal field off the Basiluzzo Islet (Aeolian Volcanic Archipelago).

Ammonium- and Fe(II)-rich fluid flows, known from deep-sea hydrothermal systems, have been extensively studied in the last decades and are considered as sites with high microbial diversity and activity. Their shallow-submarine counterparts, despite their easier accessibility, have so far been under-investigated, and as a consequence, much less is known about microbial communities inhabiting these ecosystems. A field of shallow expulsion of hydrothermal fluids has been discovered at depths of 170-400 meters off the base of the Basiluzzo Islet (Aeolian Volcanic Archipelago, Southern Tyrrhenian Sea). This area consists predominantly of both actively diffusing and inactive 1-3 meters-high structures in the form of vertical pinnacles, steeples and mounds covered by a thick orange to brown crust deposits hosting rich benthic fauna. Integrated morphological, mineralogical, and geochemical analyses revealed that, above all, these crusts are formed by ferrihydrite-type Fe3+ oxyhydroxides. Two cruises in 2013 allowed us to monitor and sampled this novel ecosystem, certainly interesting in terms of shallow-water iron-rich site. The main objective of this work was to characterize the composition of extant communities of iron microbial mats in relation to the environmental setting and the observed patterns of macrofaunal colonization. We demonstrated that iron-rich deposits contain complex and stratified microbial communities with a high proportion of prokaryotes akin to ammonium- and iron-oxidizing chemoautotrophs, belonging to Thaumarchaeota, Nitrospira, and Zetaproteobacteria. Colonizers of iron-rich mounds, while composed of the common macrobenthic grazers, predators, filter-feeders, and tube-dwellers with no representatives of vent endemic fauna, differed from the surrounding populations. Thus, it is very likely that reduced electron donors (Fe2+ and NH4+ ) are important energy sources in supporting primary production in microbial mats, which form a habitat-specific trophic base of the whole Basiluzzo hydrothermal ecosystem, including macrobenthic fauna.

Vagal Nerve Stimulation for Drug-Resistant Epilepsy: Adverse Events and Outcome in a Series of Patients with Long-Term Follow-Up.

BACKGROUND: Vagal nerve stimulation (VNS) is a palliative treatment option for drug-resistant epilepsy. The aim of this study was to describe the clinical and demographic features of selected patients scheduled for VNS and to evaluate the long-term efficacy of VNS in seizure control. MATERIALS AND METHODS: Between 2006 and 2013, 32 consecutive epileptic patients (14 male and 18 female) were enrolled at our Institute for VNS implantation. In all cases resective surgery had previously been excluded by the use of a noninvasive presurgical study protocol. Mean age was 32 years (range 18-50), and mean epilepsy duration 23 years (range 11-39). All subjects were followed-up for at least 2 years (mean 6 years, range 2-9) after VNS implantation. Patients were considered responders when a reduction of seizures of more than 50 % was reported. RESULTS: All patients had complex partial seizures, in 81 % of the patients with secondary generalization and in 56 % with drop attacks. Neurological examination revealed focal deficits in 19 % of the patients. Brain magnetic resonance imaging (MRI) was positive in 47 % of the patients. No surgical complications were observed in this series. Three patients were lost to follow-up. Twelve patients were classified as responders. Among the others, 1 patient experienced side effects (snoring and groaning during sleep) and the device was removed. CONCLUSIONS: Our data confirm that VNS is a safe procedure and a valid palliative treatment option for drug-resistant epileptic patients not suitable for resective surgery.

Hemilaminectomy for spinal meningioma: A case series of 20 patients with a focus on ventral- and ventrolateral lesions.

OBJECTIVE: To demonstrate the effectiveness and safety of hemilaminectomy in spinal-meningioma surgery, with special attention to ventral lesions. We also describe technical tips to enhance surgical-corridor width. PATIENTS AND METHODS: A total of 20 patients (14 female and 6 male) underwent hemilaminectomy for resection of a spinal meningioma between January 2005 and December 2015. Preoperative magnetic resonance imaging defined the tumor location (16 thoracic, 3 cervical, 1 lumbar) and the dural-attachment site (4 ventral, 11 ventrolateral, 3 lateral, 2 posterior). Pre- and postprocedural functional status was evaluated according to McCormick's classification. Intraoperative neurophysiological monitoring was employed in all patients. RESULTS: The unilateral approach allowed for complete resection (Simpson grade I-II resection) in 18 patients (90%), including tumors with a ventral dural attachment. In most patients (n=13), monosegmental hemilaminectomy was performed, a single patient required hemilaminectomy of 3 levels, while the remaining 6 patients underwent hemilaminectomy of 2 levels. No patients experienced either worsening of neurological status or procedure-related complications. All patients who had preoperative pain reported postoperative improvement. CONCLUSIONS: The goal of surgery for spinal tumors is to achieve gross tumor removal while minimizing morbidity. In our experience, hemilaminectomy is an effective surgical approach, even in patients with ventral- and ventrolateral spinal meningiomas. The procedure offers several advantages in terms of early patient mobilization and rehabilitation, management of postoperative pain, and preservation of spinal stability while achieving positive functional outcomes.

KCa3.1 inhibition switches the phenotype of glioma-infiltrating microglia/macrophages.

Among the strategies adopted by glioma to successfully invade the brain parenchyma is turning the infiltrating microglia/macrophages (M/MΦ) into allies, by shifting them toward an anti-inflammatory, pro-tumor phenotype. Both glioma and infiltrating M/MΦ cells express the Ca(2+)-activated K(+) channel (KCa3.1), and the inhibition of KCa3.1 activity on glioma cells reduces tumor infiltration in the healthy brain parenchyma. We wondered whether KCa3.1 inhibition could prevent the acquisition of a pro-tumor phenotype by M/MΦ cells, thus contributing to reduce glioma development. With this aim, we studied microglia cultured in glioma-conditioned medium or treated with IL-4, as well as M/MΦ cells acutely isolated from glioma-bearing mice and from human glioma biopsies. Under these different conditions, M/MΦ were always polarized toward an anti-inflammatory state, and preventing KCa3.1 activation by 1-[(2-Chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), we observed a switch toward a pro-inflammatory, antitumor phenotype. We identified FAK and PI3K/AKT as the molecular mechanisms involved in this phenotype switch, activated in sequence after KCa3.1. Anti-inflammatory M/MΦ have higher expression levels of KCa3.1 mRNA (kcnn4) that are reduced by KCa3.1 inhibition. In line with these findings, TRAM-34 treatment, in vivo, significantly reduced the size of tumors in glioma-bearing mice. Our data indicate that KCa3.1 channels are involved in the inhibitory effects exerted by the glioma microenvironment on infiltrating M/MΦ, suggesting a possible role as therapeutic targets in glioma.

Alginate-hyaluronan composite hydrogels accelerate wound healing process.

In this paper we propose polysaccharide hydrogels combining alginate (ALG) and hyaluronan (HA) as biofunctional platform for dermal wound repair. Hydrogels produced by internal gelation were homogeneous and easy to handle. Rheological evaluation of gelation kinetics of ALG/HA mixtures at different ratios allowed understanding the HA effect on ALG cross-linking process. Disk-shaped hydrogels, at different ALG/HA ratio, were characterized for morphology, homogeneity and mechanical properties. Results suggest that, although the presence of HA does significantly slow down gelation kinetics, the concentration of cross-links reached at the end of gelation is scarcely affected. The in vitro activity of ALG/HA dressings was tested on adipose derived multipotent adult stem cells (Ad-MSC) and an immortalized keratinocyte cell line (HaCaT). Hydrogels did not interfere with cell viability in both cells lines, but significantly promoted gap closure in a scratch assay at early (1 day) and late (5 days) stages as compared to hydrogels made of ALG alone (p<0.01 and 0.001 for Ad-MSC and HaCaT, respectively). In vivo wound healing studies, conducted on a rat model of excised wound indicated that after 5 days ALG/HA hydrogels significantly promoted wound closure as compared to ALG ones (p<0.001). Overall results demonstrate that the integration of HA in a physically cross-linked ALG hydrogel can be a versatile strategy to promote wound healing that can be easily translated in a clinical setting.

Morphology changes in human lung epithelial cells after exposure to diesel exhaust micron sub particles (PM1.0) and pollen allergens.

In the recent literature there has been an increased interest in the effects of particulate matter on the respiratory tract. The objective of this study was to use an in vitro model of type II lung epithelium (A549) to evaluate the cell ability to take up sub-micron PM(1.0) particles (PM(1.0)), Parietaria officinalis (ALL), and PM(1.0) + ALL together. Morphological analysis performed by Transmission Electron Microscope (TEM) showed that PM and ALL interacted with the cell surface, then penetrating into the cytoplasm. Each single treatment was able to point out a specific change in the morphology. The cells treated appear healthy and not apoptotic. The main effect was the increase of: multilamellar bodies, lysosomal enzymes, microvilli, and presence of vesicle/vacuoles containing particles. These observations demonstrate morphological and functional alterations related to the PM(1.0) and P. officinalis and confirm the induction of the inflammatory response in lung cells exposed to the inhalable particles.

Adipocyte-released insulin-like growth factor-1 is regulated by glucose and fatty acids and controls breast cancer cell growth in vitro.

AIMS/HYPOTHESIS: Type 2 diabetes and obesity are associated with increased risk of site-specific cancers. We have investigated whether metabolic alterations at the level of adipose-derived differentiating cells may affect specific phenotypes of breast cancer cells. METHODS: Growth profiles of breast cancer cell lines were evaluated in co-cultures with differentiated adipocytes or their precursor cells and upon treatment with adipocyte conditioned media. Production and release of cytokines and growth factors were assessed by real-time RT-PCR and multiplex-based ELISA assays. RESULTS: Co-cultures with either differentiated mouse 3T3-L1 or human mammary adipocytes increased viability of MCF-7 cells to a greater extent, when compared with their undifferentiated precursors. Adipocytes cultured in 25 mmol/l glucose were twofold more effective in promoting cell growth, compared with those grown in 5.5 mmol/l glucose, and activated mitogenic pathways in MCF-7 cells. Growth-promoting action was also enhanced when adipocytes were incubated in the presence of palmitate or oleate. Interestingly, 3T3-L1 and human adipocytes released higher amounts of keratinocyte-derived chemokine/IL-8, the protein 'regulated upon activation, normally T expressed, and secreted' (RANTES), and IGF-1, compared with their precursor cells. Their levels were reduced upon incubation with low glucose and enhanced by fatty acids. Moreover, both undifferentiated cells and differentiated adipocytes from obese individuals displayed about twofold higher IGF-1 release and MCF-7 cell growth induction than lean individuals. Finally, inhibition of the IGF-1 pathway almost completely prevented the growth-promoting effect of adipocytes on breast cancer cells. CONCLUSIONS/INTERPRETATION: IGF-1 release by adipocytes is regulated by glucose and fatty acids and may contribute to the control of cancer cell growth in obese individuals.

Inflammatory effects on human lung epithelial cells after exposure to diesel exhaust micron sub particles (PM1.0) and pollen allergens.

Asthma is currently defined as a chronic inflammatory disease of the airway. Several evidence indicate that vehicle emissions in cities is correlated with the allergic respiratory diseases. In the present study, we evaluated in the A549 cells the production and release of IL-4, IL-5 and IL-13 after treatment with sub-micron PM(1.0) particles (PM(1.0)), Parietaria officinalis (ALL), and PM(1.0) + ALL together. Our data demonstrated that PM(1.0) + ALL together exhibited the greatest capacity to induce A549 cells to enhance the expression of IL-4 and IL-5 compared with the only PM(1.0) or ALL treatment. Interestingly, IL-13 that is necessary for allergen-induced airway hyper responsiveness, is increased in cells treated with PM(1.0) + ALL together, but is higher expressed when the cells are treated only with the allergen. Our data support the hypothesis that the urban environment damage the acinar lung units and activates cells of the immune system.

Single brain metastases from cervical carcinoma: report of two cases and critical review of the literature.

Single brain metastases from cervical carcinomas are rare. We report two cases of solitary brain metastases, showing different histological types, which have been excised with microsurgical technique. Neuroendocrine differentiation does not seem to be connected to clinical behavior, indeed a poor prognosis depends on poorly differentiated histological types. In our cases, brain metastases were a late event and they have been successfully excised in microsurgery, thanks to their solitary and resectable nature, and a well-controlled primary disease.

Percutaneous radiofrequency ablation of hepatocellular carcinoma compared to percutaneous ethanol injection in treatment of cirrhotic patients: an Italian randomized controlled trial.

AIM: To compare 5-year survival of patients with a single hepatocellular carcinoma≤3 cm randomly assigned to receive percutaneous ethanol injection or radiofrequency ablation. PATIENTS AND METHODS: A total of 285 patients (192 males, mean age 70 years), with a single hepatocellular carcinoma (mean diameter 2.2 cm) were randomly assigned to receive percutaneous ethanol injection (n=143) or radiofrequency ablation (n=142). The primary endpoint of the study was 5-year survival. RESULTS: Overall 143 patients underwent percutaneous ethanol injection and 128 radiofrequency ablation. In consideration of segmental location, in fact, 14 patients with 14 hepatocellular carcinomas could not be treated with established radiofrequency and were treated with percutaneous ethanol injection; these patients were not included in the survival evaluation. In the percutaneous ethanol injection and in the radiofrequency ablation groups, 3- and 5-year survival rates of 74% and 68%, and 78% and 68%, and 79% and 70% [corrected] respectively, were observed (p=n.s). In the percutaneous ethanol injection group, 3- and 5-year local recurrence rates were 9.4% and 12.8% respectively; in the radiofrequency group, the 3 and 5 years local recurrence rates were 7.8% and 11.7%, respectively (p=n.s.). The overall costs of percutaneous ethanol injection and radiofrequency ablation were 1359 Euros and 171.000 Euros, respectively (p<0.0001) CONCLUSION: Percutaneous ethanol injection and radiofrequency ablation conferred similar 5-year survival. Feasibility is not the same for both procedures. Percutaneous ethanol injection is much cheaper than radiofrequency ablation and should be considered whether in poor and rich countries.

Ectopic thymus presenting as neck mass in a neonate: a case report.

Neck masses are rare in newborns and can represent a big challenge for the paediatric surgeons. Different histological types are reported in the recent literature; while 80% of neck masses are benign, the pediatric surgeon is often called upon to assist in the evaluation, diagnosis and treatment. A two-month old baby was evaluated for an asymptomatic left sided cervical mass, presented at birth, which slowly increased in size. A magnetic resonance imaging scan was performed, with evidence of capsulated solid neck mass, lateral to the sternocleidomastoid muscle, not including the major vassel structures of the neck. The patient underwent surgical excision in the criteria to define the histology of the mass. A well capsulated mass was detected at surgery. At histology, an ectopic cervical thymus tissue was reported. The ectopic cervical thymus is an uncommon entity with only 91 cases reported; only nine occurred in infants, two in the neonatal period. According to the authors, in case of enlarging solid neck mass with unclear imaging or clinical data, complete surgical resection is the only and safe procedure to perform.

A Troubling Diagnosis of Verrucous Squamous Cell Carcinoma ("the Bad Kind" of Keratosis) and the Need of Clinical and Pathological Correlations: A Review of the Literature with a Case Report.

Verrucous carcinoma (also known as Ackerman tumor) is an uncommon exophytic low-grade well-differentiated variant of squamous cell carcinoma. This neoplasm typically involves the oral cavity, larynx, genitalia, skin, and esophagus. It is well known for its locally aggressiveness and for its clinically slow-growing behaviour with minimal metastatic potential. Verrucous carcinoma of oral cavity is so closely aligned with the use of snuff and chewing tobacco that it has been called the "snuff dipper's cancer". Recent studies have proved the role of HPV. The typical clinical presentation of oral verrucous carcinoma has long been known, as its remarkably innocuous appearance and biological behaviour. In this work, we report a review of the scientific literature and describe a troublesome case of oral verrucous cancer.

Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide.

Epigenetic silencing of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene by promoter methylation is correlated with improved progression-free survival (PFS) and overall survival (OS) in adult patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. The aim of this study is to determine the correlation between MGMT and survival in elderly patients with GBM treated with radiotherapy (RT) and temozolomide (TMZ). Eighty-three patients aged 70 years or older with histologically confirmed GBM treated with RT plus TMZ between February 2005 and September 2009 were investigated in this study. The methylation status of the MGMT promoter was determined by polymerase chain reaction analysis. Median PFS and OS were 7.5 and 12.8 months, respectively. The MGMT promoter was methylated in 42 patients (50.6%) and unmethylated in 41 patients (49.4%). Median OS was 15.3 months in methylated patients and 10.2 months in unmethylated patients (P = 0.0001). Median PFS was 10.5 months in methylated tumors and 5.5 months in unmethylated tumors (P = 0.0001). On multivariate analysis MGMT methylation status emerged as the strongest independent prognostic factor for OS and PFS (P = 0.004 and P = 0.005, respectively). The results of the present study suggest that MGMT methylation status might be an important prognostic factor associated with better OS and PFS in elderly patients with GBM treated with RT and TMZ.

Tissue plasminogen activator and urokinase plasminogen activator in human epileptogenic pathologies.

A growing body of evidence demonstrates the involvement of plasminogen activators (PAs) in a number of physiologic and pathologic events in the CNS. Induction of both tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) has been observed in different experimental models of epilepsy and tPA has been implicated in the mechanisms underlying seizure activity. We investigated the expression and the cellular distribution of tPA and uPA in several epileptogenic pathologies, including hippocampal sclerosis (HS; n=6), and developmental glioneuronal lesions, such as focal cortical dysplasia (FCD, n=6), cortical tubers in patients with the tuberous sclerosis complex (TSC; n=6) and in gangliogliomas (GG; n=6), using immuno-cytochemical, western blot and real-time quantitative PCR analysis. TPA and uPA immunostaining showed increased expression within the epileptogenic lesions compared to control specimens in both glial and neuronal cells (hippocampal neurons in HS and dysplastic neurons in FCD, TSC and GG specimens). Confocal laser scanning microscopy confirmed expression of both proteins in astrocytes and microglia, as well as in microvascular endothelium. Immunoblot demonstrated also up-regulation of the uPA receptor (uPAR; P<0.05). Increased expression of tPA, uPA, uPAR and tissue PA inhibitor type mRNA levels was also detected by PCR analysis in different epileptogenic pathologies (P<0.05). Our data support the role of PA system components in different human focal epileptogenic pathologies, which may critically influence neuronal activity, inflammatory response, as well as contributing to the complex remodeling of the neuronal networks occurring in epileptogenic lesions.

Successful treatment of Cryptococcal meningitis with a combination of liposomal amphotericin B, flucytosine and posaconazole: two case reports.

Cryptococcus neoformans CNS infection frequently affects HIV-infected patients and is often lethal, despite antifungal therapy. The most recent treatment guidelines for Cryptococcal meningitis recommend therapy with lyposomal amphotericin B and possible association with flucitosine. However, clinical response rates in HIV-infected patients are not satisfactory, with a persistent high mortality rate and long term therapy is affected by a high risk of major side effects. Posaconazole, the latest broad-spectrum azole, with both in vitro- and in vivo-documented potent activity against C. neoformans, clearly showed no antagonism with amphotericin B, echinocandins or flucytosine and it has both in vitro and in vivo agonistic activity with flucytosine against C. neoformans. We report two cases of successful salvage therapy based on the addition of posaconazole to a standard treatment based on liposomal amphotericin B and Flucytosine. In addition we used posaconazole also in a maintenance therapeutic regimen with no evidence of recurrences in the follow up of these patients. Our report confirms that posaconazole has clinical activity in the CNS against C. neoformans infection. In addition posaconazole showed no antagonism with any other currently available antifungal agent, and was in fact synergistic to some of them (flucytosine); consequently, it seems to be an ideal candidate for antimicrobial combination salvage therapies. Finally posaconazole represents a good alternative to parenteral therapy and an ideal candidate for long-term maintenance therapy due to its competent toxicity profile and oral bioavailability.

The improvement of ischemia/reperfusion injury by erythropoetin is not mediated through bone marrow cell recruitment in rats.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure in kidney transplantation; however, the mechanisms of kidney damage and repair are not yet clear. So far no treatment has been effective to prevent I/R injury. In the present study we evaluated the effect of erythropoetin (EPO) in I/R injury in rats. We investigated the role of bone marrow cells (BMC) in kidney repair and the effect of EPO on BMC recruitment. MATERIALS AND METHODS: Female Sprague Dawley rats transplanted with male BMCs underwent I/R injury. In the treatment group rats received 5000 IU of EPO 30 minutes before renal ischemia. At 2 and 4 weeks after I/R, rats were humanely killed and we measured creatinine clearance (glomerular filtration rate [GFR]), proteinuria, and body weight (BW). Renal tissue was harvested for histologic and molecular analysis. Fluorescein in situ hybridization (FISH) and TUNEL were used to determined the presence of male cell chimerism and apoptosis in renal tissue. RESULTS: At 4 weeks after I/R, EPO significantly improved GFR (1.8 +/- 0.2 vs 1.2 +/- 0.14 mL/min; P < .05). No significant differences between EPO and control rats were observed in proteinuria, BW, and hemoglobin levels at 2 and 4 weeks. After death, the kidney showed only minimal tubulointerstitial changes, which were more marked in control rats. FISH analysis demonstrated a low degree of microchimerism, not significantly different between EPO and control rats. Apoptosis decreased between 2 and 4 weeks after I/R, in both EPO and control groups. CONCLUSION: EPO improved GFR and injury at 4 weeks after I/R; however, it did not enhance the recruitment of BMC.