Three Decades of Experience with Aortic Prosthetic Valve Endocarditis

The objective of this study was to evaluate early and long-term outcomes of patients with aortic prosthetic valve endocarditis (a-PVE) treated with a prosthetic aortic valve (PAV), prosthetic valved conduit (PVC), or cryopreserved aortic homograft (CAH). A total of 144 patients, 115 male and 29 female, aged 67 +/- 12 years, underwent surgery for a-PVE at our institution between 1994 and 2021. Median time from the original cardiac surgery was 1.9 [0.6-5.6] years, and 47 (33%) patients developed an early a-PVE. Of these patients, 73 (51%) underwent aortic valve replacement (AVR) with a biological or mechanical PAV, 12 (8%) underwent aortic root replacement (ARR) with a biological or mechanical PVC, and 59 (42%) underwent AVR or ARR with a CAH. Patients treated with a CAH had significantly more circumferential annular abscess multiple valve involvement, longer CPB and aortic cross-clamping times, and needed more postoperative pacemaker implantation than patients treated with a PAV. No difference was observed in survival, reoperation rates, or recurrence of IE between patients treated with a PAV, a PVC, or a CAH. CAHs are technically more demanding and more often used in patients who have extensive annular abscess and multiple valve involvement. However, the use of CAH is safe in patients with complex a-PVE, and it shows excellent early and long-term outcomes

Splenic Ly6Chi monocytes are critical players in dystrophic muscle injury and repair

Dystrophic muscle is characterised by chronic injury, and a steady recruitment of inflammatory Ly6Chi monocytes. Recent studies have identified the spleen as the dominant reservoir of these cells during chronic inflammation. Here we investigated the hitherto unexplored contribution of splenic Ly6Chi monocytes to dystrophic muscle pathology. Using the mdx mouse model of muscular dystrophy, we show that Ly6Chi monocytes accumulate in great numbers in the spleen over the course of the disease. The chemokine receptor CCR2 was upregulated on Ly6Chi monocytes in mdx spleen before disease onset, thereby enabling their recruitment to dystrophic muscle. Splenectomy performed before disease onset significantly reduced the number of Ly6Chi monocytes infiltrating dystrophic limb muscle. Moreover, in the absence of splenic Ly6Chi monocytes there was a significant reduction in dystrophic muscle inflammation and necrosis, along with improved regeneration during early disease. However, during late disease, lack of splenic Ly6Chi monocytes adversely affected muscle fiber repair, due to a delay in the phenotypic shift of pro-inflammatory F4/80+/Ly6Chi/CD206lo to anti-inflammatory F4/80+/Ly6Clo/CD206+ macrophages. Overall, we show that the spleen is an indispensable source of Ly6Chi monocytes in muscular dystrophy, and that splenic monocytes are critical players in both muscle fiber injury and repair

Surgical Treatment of Paget Disease of the Vulva

ObjectiveThe aim of the study was to evaluate the risk of recurrence according to the surgical margin status and the presence of invasion or of superficially invasive carcinoma in patients with extramammary Paget disease (EMPD) of the vulva, who underwent elective surgical treatment.Materials and MethodsWe performed a retrospective analysis of 27 patients with first diagnosis of extramammary Paget disease of the vulva, who underwent primary and elective surgical treatment from January 1989 to December 2014. A p value of less than .05 was considered statistically significant. Multivariable logistic regression was performed to adjust for confounding factors.ResultsWe observed invasive disease in 11 cases, with microinvasion in 8 of them. A positive surgical margin was found in 10 patients. During a median follow-up period of 79.5 months, 8 patients (29.6%) showed a first recurrence after a median (range) time of 4.9 (2.3-7.1) years. No significant differences were observed between patients with recurrence and patients without recurrence with respect to age, number of vulvar sectors involved, bilaterality and multifocality, presence of invasion or microinvasion, and surgical margin status. However, during the follow-up period, the presence of invasion was higher (67% vs 41%) in patients with recurrence compared with patients without recurrence.ConclusionsThe rate of recurrence of the disease after therapy is high. Patients should be subjected to a close and long-term follow-up to identify those who must undergo further treatment, especially if they presented with an invasive or even microinvasive disease. A free margin of no greater than 1 to 2 cm might be the most appropriate surgical choice

Adjunctive Clotiapine for the Management of Delusions in Two Adolescents with Anorexia Nervosa

open7noClotiapine is an atypical antipsychotic indicated for the management of a series of acute psychotic disorders. The current literature lacks evidence concerning the tolerability and clinical use of this drug in the management of individuals with anorexia nervosa (AN). In this study, we report two cases of adolescents with AN, treated with clotiapine. The reason for the administration of clotiapine was, for both patients, the manifestation of bizarre delusions concerning food and calories. Patient 1 presented a presyncope after the first dose of clotiapine, and treatment was rapidly discontinued. Patient 2 was treated with clotiapine for 9 months; doses were titrated from 20 mg/day to 70 mg/day, with an improvement in the reported delusions, which also enhanced compliance with psychological and nutritional interventions. EKG, QTc, white blood count, and red blood count were not relevantly influenced by the introduction of clotiapine in either patient. No extrapyramidal effect was documented. These reports stress the need for further studies assessing the tolerability and potential effect of clotiapine in treating adolescents with AN and delusional symptomatology.openJacopo Pruccoli , Giulia Joy Leone, Cristina Di Sarno, Luigi Vetri , Giuseppe Quatrosi , Michele Roccella, Antonia ParmeggianiJacopo Pruccoli , Giulia Joy Leone, Cristina Di Sarno, Luigi Vetri , Giuseppe Quatrosi , Michele Roccella, Antonia Parmeggian

Vaginal Intraepithelial Neoplasia: Histopathological Upgrading of Lesions and Evidence of Occult Vaginal Cancer

Objective The aim of this study was to analyze women treated with excisional procedures for vaginal high-grade squamous intraepithelial lesions (HSILs). The histopathological upgrading of the lesions previously detected on vaginal biopsy and the presence of occult invasive vaginal cancer in the specimens excised were investigated, to identify a higher risk subset of women.Materials and Methods A retrospective analysis of the medical records of 86 women with a biopsy histopathologic diagnosis of vaginal HSIL (vaginal intraepithelial neoplasias [VaINs]: VaIN2 and VaIN3) and subsequent excisional therapy, consecutively referred to the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014, was performed.Results Of the 86 patients, 4 cases (4.6%) of occult vaginal cancer were detected, all of them in women previously diagnosed with VaIN3 on biopsy (4/39 cases, 10.3%). Women with diagnosis of VaIN2 on biopsy showed an upgrading of lesions, with diagnosis of VaIN3 on the final specimen in 5 (10.6%) of 47 cases, with no cases of VAIN2 upgraded to invasive cancer. In 33.3% of the women initially diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus-related disease, a final histopathological upgrading of lesions emerged. Furthermore, tobacco use was significantly related to the histopathological upgrading of lesions previously detected on vaginal biopsy.Conclusions Women diagnosed with VaIN3 should be treated with excisional procedures as first-line surgical approach, given the risk of occult invasive disease in 10% of the cases. Women diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus-related cervical diseases should always be carefully evaluated and possibly excised, given the higher risk of histopathological upgrading of lesions and thus the potential risk of occult vaginal cancer. Tobacco users should be considered as high-risk group

The Herschel Virgo Cluster Survey - XIII. Dust in early-type galaxies

Aims. We study the dust content of a large optical input sample of 910 early-type galaxies (ETG) in the Virgo cluster, extending also to the dwarf ETG, and examine the results in relation with those on the other cold ISM components. Methods. We searched for far-infrared emission in all galaxies of the input sample using the 250 micron image of the Herschel Virgo Cluster Survey (HeViCS). This image covers a large fraction of the cluster. For the detected ETG we measured fluxes in 5 bands from 100 to 500 micron, and estimated the dust mass and temperature with modified black-body fits. Results. Dust is detected above the completeness limit of 25.4 mJy at 250 micron in 46 ETG, 43 of which are in the optically complete part of the input sample. In addition dust is present at fainter levels in another 6 ETG. We detect dust in the 4 ETG with synchrotron emission, including M 87. Dust appears to be much more concentrated than stars and more luminous ETG have higher dust temperatures. Dust detection rates down to the 25.4 mJy limit are 17% for ellipticals, about 40% for lenticulars (S0 + S0a) and around 3% for dwarf ETG. Dust mass does not correlate clearly with stellar mass and is often much more than that expected for a passive galaxy in a closed-box model. The dust-to-stars mass ratio anticorrelates with galaxy luminosity, and for some dwarf ETG reaches values as high as for dusty late-type galaxies. In the Virgo cluster slow rotators appear more likely to contain dust than fast ones. Comparing the dust results with those on HI from ALFALFA, there are only 8 ETG detected both in dust and in HI in the HeViCS area; 39 have dust but only an upper limit on HI, and 8 have HI but only an upper limit on dust. The locations of these galaxies in the cluster are different, with the dusty ETG concentrated in the densest regions, while the HI rich ETG are at the periphery.Comment: Accepted by Astronomy and Astrophysics; modified to reflect the on-line forthcoming version on the A&A web sit

Laser Excisional Treatment for Vaginal Intraepithelial Neoplasia to Exclude Invasion

Objective: We undertook a retrospective analysis of the incidence of complications of carbon dioxide (CO2) laser excision for high-grade vaginal intraepithelial neoplasia (HG-VaIN).Materials and Methods: Retrospective large case series on 128 CO2 laser excisions for HG-VaIN in 106 women treated at the Department of Gynecologic Oncology, Oncologic Referral Center, Aviano, Italy. These procedures were performed under local anesthesiawith a 20-Wcontinuous laser beam focused to a 0.2-mm spot size. Complications were defined as "minor" when limited to vagina, and "major" when surrounding organs were injured or the vaginal vault was opened. To identify possible factors associated with surgical complications, we performed a univariate analysis with the t test for continuous variables and x(2) or Fisher exact test for qualitative variables as appropriate.Results: The overall rate of complication was 7.8% (10/128); nine of themwere vaginal bleeding, and only one (0.8%) was amajor complication with vaginal vault perforation. A greater number of previous destructive treatments and of two or more previous laser vaginal excisional treatments was present in patients with complications compared with ones without complications (10% vs 3.9 %, p = .92, and 30% vs 15.2%, p = .44, respectively), although these differences were not statistically significant. A total of 10.5% (6/57) of occult vaginal cancer was detected in women with initial diagnosis of VaIN3 (HG-VaIN) on biopsy.Conclusions: Carbon dioxide laser excision for HG-VaIN seems to be a safe approach with low rate of complications, probably because of the better accuracy achieved by CO2 laser resections, and permits diagnosis of occult invasive disease

Clinical Effectiveness and Pharmacokinetics of Dalbavancin in Treatment-Experienced Patients with Skin, Osteoarticular, or Vascular Infections

Dalbavancin (DBV) is a lipoglycopeptide approved for the treatment of Gram-positive infections of the skin and skin-associated structures (ABSSSIs). Currently, its off-label use at different dosages for other infections deserves attention. This work aimed to study the clinical effectiveness and tolerability of DBV in outpatients with ABSSSIs, osteoarticular (OA), or other infections, treated with either one or two 1500 mg doses of dalbavancin, for different scheduled periods. A liquid chromatography–tandem mass spectrometry method was used to measure total DBV concentrations. PK/PD parameters and the clinical and microbiological features of this cohort were evaluated in order to investigate the best predictors of treatment success in real-life settings. Of the 76 screened patients, 41 completed the PK study. Long-term PK was comparable to previous studies and showed significant differences between genders and dosing schedules. Few adverse events were observed, and treatment success was achieved in the vast majority of patients. Failure was associated with lower PK parameters, particularly C(max). Concluding, we were able to describe DBV PK and predictors of treatment success in selected infections in this cohort, finding DBV C(max) as a possible candidate for therapeutic drug-monitoring purposes, as well as highlighting the dual-dose one-week-apart treatment as the optimal choice for OA infections

Long-Term Pharmacokinetics of Dalbavancin in ABSSSI and Osteoarticular Settings: A Real-Life Outpatient Context

Dalbavancin is a lipoglycopeptide approved for treatment of Gram-positive infections of skin and skin-associated structures (ABSSSI). Currently, off-label use at high dosages for osteoarticular infections deserves attention. This work aimed to study the long-term plasma pharmacokinetics of dalbavancin in outpatients with ABSSSI or osteoarticular infections, treated either with one or two 1500 mg doses of dalbavancin. A liquid chromatography-tandem mass spectrometry method was used to measure total dalbavancin concentrations in plasma samples. The results were analyzed through a non-compartmental analysis (NCA). Breakpoint minimum inhibitory concentration (MIC) was used to calculate AUC/MIC and T > MIC parameters, adjusted by 93% protein binding. A total of 14 patients were enrolled, 11 with osteoarticular infection and 3 with ABSSSI. Long-term pharmacokinetics showed median T > MIC (0.125 mg/L) of 11.9 and 13.7 weeks for single and dual dose, respectively. Similarly, median AUC0-2w/MIC ratios of 20,590 and 31,366 were observed for single and dual dose regimens, respectively. No adverse events were observed, and treatment success was achieved in 12/14 patients. Failure was associated with the worst clinical conditions, bone infections, and single dose. The results of this study show that dalbavancin exposure exceeds previously suggested pharmacodynamic targets. Optimization of these targets is needed for the osteoarticular setting