Hemolytic Anemia as Presentation of T-Cell Large Granular Lymphocytic Leukemia After Kidney Transplantation: A Case Report

T-cell large granular lymphocytic (T-LGL) leukemia is a rare clonal proliferation presenting with cytopenia, splenomegaly, and autoimmune manifestations. It has rarely been described in recipients of solid organ transplants. We report the clinical case of a young kidney transplant recipient that developed T-LGL leukemia 3 years after kidney transplantation. The disorder manifested with a severe form of autoimmune hemolytic anemia in the absence of other laboratory abnormalities. The anemia was successfully treated with an intense course of corticosteroids ands witch of immunosuppressive therapy from a calcineurin inhibitor to sirolimus, a mammalian target of rapamycin inhibitor. Our case shows that autoimmune hemolytic anemia can be a life-threatening manifestation of T-LGL disease. The antiproliferative effects of sirolimus may be useful in the treatment of symptoms of T-LGL leukemia in kidney transplantation

Comparison Between Kidney Transplantation After Circulatory Death and After Brain Death: A Monocentric Retrospective Study After 1 Year of Follow-up

Background: Donation after circulatory death (DCD) is a solid resource to widen the kidney donor pool. Italian activity has grown in the last years with encouraging results. Our center has been active in DCD kidney transplantation (KTX) since November 2017, providing 22.5% of Italian DCD donations in 2018. We present a single-center retrospective analysis after a 1-year follow-up comparing DCD and donation after brain death (DBD) KTX outcomes. Methods: DCD (controlled only) and DBD KTX performed in our center from November 2017 to December 2018 were considered. All DCDs underwent in situ normothermic perfusion with extracorporeal membrane oxygenation, ex situ hypothermic oxygenated perfusion, and renal biopsy prior to allocation. We considered features of donors and recipients, immunosuppressive regimen, delayed graft function (DGF), primary nonfunction (PNF), graft and patient survival (Kaplan-Meier), creatinine, and estimated glomerular filtration rate at 1 year. Mean comparison with a Student t test and with \u3c72 test for frequencies were elaborated. Results: Twenty-eight DBD, 18 double (64.3%) and 10 single (35.7%), were performed; 7 DCD, 3 double (42.8%) and 4 single (57.2%), were performed. By comparing single and double KTX, no statistically significant difference was found. We recorded 7 DGFs (25%) in DBD and 1 (14.3%) in the DCD group (P > .99) and no PNF. No graft was lost during the first year. One-year estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration) was, respectively, 62.7 \ub1 25.3 and 54.71 \ub1 14.66 mL/min (P = .25). DBD patient survival rate was 92.8%, DCD was 100%, and Kaplan-Meier was not statistically significant (P = .72). Conclusions: Controlled DCD is a valid resource for KTX, with similar outcomes to DBD. A multidisciplinary donor evaluation, combining clinical, perfusion, and histologic data in the allocation process, allows excellent results

Prediction of severe thunderstorm events with ensemble deep learning and radar data

The problem of nowcasting extreme weather events can be addressed by applying either numerical methods for the solution of dynamic model equations or data-driven artificial intelligence algorithms. Within this latter framework, the most used techniques rely on video prediction deep learning methods which take in input time series of radar reflectivity images to predict the next future sequence of reflectivity images, from which the predicted rainfall quantities are extrapolated. Differently from the previous works, the present paper proposes a deep learning method, exploiting videos of radar reflectivity frames as input and lightning data to realize a warning machine able to sound timely alarms of possible severe thunderstorm events. The problem is recast in a classification one in which the extreme events to be predicted are characterized by a an high level of precipitation and lightning density. From a technical viewpoint, the computational core of this approach is an ensemble learning method based on the recently introduced value-weighted skill scores for both transforming the probabilistic outcomes of the neural network into binary predictions and assessing the forecasting performance. Such value-weighted skill scores are particularly suitable for binary predictions performed over time since they take into account the time evolution of events and predictions paying attention to the value of the prediction for the forecaster. The result of this study is a warning machine validated against weather radar data recorded in the Liguria region, in Italy

Variable echo time imaging for detecting the short T2* components of the sciatic nerve: a validation study

OBJECTIVE: The aim of this study was to develop and validate an MRI protocol based on a variable echo time (vTE) sensitive to the short T2* components of the sciatic nerve. MATERIALS AND METHODS: 15 healthy subjects (M/F: 9/6; age: 21-62) were scanned at 3T targeting the sciatic nerve at the thigh bilaterally, using a dual echo variable echo time (vTE) sequence (based on a spoiled gradient echo acquisition) with echo times of 0.98/5.37 ms. Apparent T2* (aT2*) values of the sciatic nerves were calculated with a mono-exponential fit and used for data comparison. RESULTS: There were no significant differences in aT2* related to side, sex, age, and BMI, even though small differences for side were reported. Good-to-excellent repeatability and reproducibility were found for geometry of ROIs (Dice indices: intra-rater 0.68-0.7; inter-rater 0.70-0.72) and the related aT2* measures (intra-inter reader ICC 0.95-0.97; 0.66-0.85) from two different operators. Side-related signal-to-noise-ratio non-significant differences were reported, while contrast-to-noise-ratio measures were excellent both for side and echo. DISCUSSION: Our study introduces a novel MR sequence sensitive to the short T2* components of the sciatic nerve and may be used for the study of peripheral nerve disorders

Clinical outcome of kidney transplantation in HIV-infected recipients: a retrospective study

Kidney transplantation is a safe and effective option for HIV-positive (HIV+) patients. We conducted a retrospective study on HIV+ kidney transplant recipients who underwent transplantation from March 2008 to September 2016.Inclusion criteria for transplantation were CD4þ T-cell count 200 per mm3 and undetectable HIV load. The current study reports the outcome of 19 HIV+ recipients, mostly of Caucasian origin (79%) with a median age of 50 years (interquartile range [IQR], 42–52), who were followed up for a median period of 2.4 years (IQR, 1.2–4.6) after transplantation. Compared with HIV-negative (HIV-) controls, HIV+ recipients had similar one- and three-year graft and patient survival, but significantly lower five-year patient survival (P¼0.03). The differences in graft outcome became less evident with the analysis of death-censored graft survival rates. Cumulative incidence of allograft rejection at one year was 32.9%. Rates of infections were not particularly elevated and HIV replication remained well controlled in all but one patient. A high prevalence of metabolic and endocrine complications (68%) was reported after transplantation. Further studies are needed to evaluate long-term outcomes of HIV+ recipients who underwent kidney transplantation

Osteonecrosis of the jaws in patients assuming oral bisphosphonates for osteoporosis: A retrospective multi-hospital-based study of 87 Italian cases

BACKGROUND: Bisphosphonates (BPs) are currently the chief drugs for the prevention/treatment of osteoporosis; one of their adverse effects is the osteonecrosis of the jaw (BRONJ). The primary endpoints of this multi-center cross-sectional study are: i) an observation of the clinical features of BRONJ in 87 osteoporotic, non-cancer patients; and ii) an evaluation of their demographic variables and comorbidities. METHODS: 87 BRONJ patients in therapy for osteoporosis with BPs from 8 participating clinical Italian centers were consecutively identified and studied. After BRONJ diagnosis and staging, comorbidities and data relating to local and drug-related risk factors for BRONJ were collected. RESULTS: 77/87 (88.5%) patients in our sample used alendronate as a BP type; the duration of bisphosphonate therapy ranged from 2 to 200 months, and 51.7% of patients were in treatment for ≤ 38 months (median value). No comorbidities or local risk factors were observed in 17 (19.5%) patients, indicating the absence of cases belonging to BRONJ forms triggered by surgery. BRONJ localization was significantly associated with age: an increased risk of mandible localization (p=0.002; OR=6.36, 95%CI=[1.89; 21.54]) was observed for those over 72 yrs. At multivariate analysis, the increased risk of BRONJ in the mandible for people over 72 yrs (OR'=6.87, 95%CI=[2.13; 2.21]) was confirmed for a BP administration >56 months (OR'=4.82, 95%CI=[2.13; 22.21]). CONCLUSION: Our study confirms the fundamental necessity of applying protocols of prevention in order to reduce the incidence of BRONJ in osteoporotic, non-cancer patients in the presence of comorbidities and/or local risk factor as well as, less frequently, in their absence

Pilot Study on Quantitative Cervical Cord and Muscular MRI in Spinal Muscular Atrophy: Promising Biomarkers of Disease Evolution and Treatment?

Introduction: Nusinersen is a recent promising therapy approved for the treatment of spinal muscular atrophy (SMA), a rare disease characterized by the degeneration of alpha motor neurons (αMN) in the spinal cord (SC) leading to progressive muscle atrophy and dysfunction. Muscle and cervical SC quantitative magnetic resonance imaging (qMRI) has never been used to monitor drug treatment in SMA. The aim of this pilot study is to investigate whether qMRI can provide useful biomarkers for monitoring treatment efficacy in SMA. Methods: Three adult SMA 3a patients under treatment with nusinersen underwent longitudinal clinical and qMRI examinations every 4 months from baseline to 21-month follow-up. The qMRI protocol aimed to quantify thigh muscle fat fraction (FF) and water-T2 (w-T2) and to characterize SC volumes and microstructure. Eleven healthy controls underwent the same SC protocol (single time point). We evaluated clinical and imaging outcomes of SMA patients longitudinally and compared SC data between groups transversally. Results: Patient motor function was stable, with only Patient 2 showing moderate improvements. Average muscle FF was already high at baseline (50%) and progressed over time (57%). w-T2 was also slightly higher than previously published data at baseline and slightly decreased over time. Cross-sectional area of the whole SC, gray matter (GM), and ventral horns (VHs) of Patients 1 and 3 were reduced compared to controls and remained stable over time, while GM and VHs areas of Patient 2 slightly increased. We found altered diffusion and magnetization transfer parameters in SC structures of SMA patients compared to controls, thus suggesting changes in tissue microstructure and myelin content. Conclusion: In this pilot study, we found a progression of FF in thigh muscles of SMA 3a patients during nusinersen therapy and a concurrent slight reduction of w-T2 over time. The SC qMRI analysis confirmed previous imaging and histopathological studies suggesting degeneration of αMN of the VHs, resulting in GM atrophy and demyelination. Our longitudinal data suggest that qMRI could represent a feasible technique for capturing microstructural changes induced by SMA in vivo and a candidate methodology for monitoring the effects of treatment, once replicated on a larger cohort

Oncological outcomes in fertility-sparing treatment in stage IA-G2 endometrial cancer

Background: The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients desiring pregnancy, fertility-sparing treatment (FST) can be adopted. Our review aims to collect the most incisive studies about the possibility of conservative management for patients with grade 2, stage IA EC. Different approaches can be considered beyond demolition surgery, such as local treatment with levonorgestrel-releasing intra-uterine device (LNG-IUD) plus systemic therapy with progestins. Study design: Our systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, EMBASE, and Scopus databases were consulted, and five studies were chosen based on the following criteria: patients with a histological diagnosis of EC stage IA G2 in reproductive age desiring pregnancy and at least one oncological outcome evaluated. Search imputes were “endometrial cancer” AND “fertility sparing” AND “oncologic outcomes” AND “G2 or stage IA”. Results: A total of 103 patients were included and treated with a combination of LNG-IUD plus megestrol acetate (MA) or medroxyprogesterone acetate (MPA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, hysteroscopic resectoscope (HR), and dilation and curettage (D&C). There is evidence of 70% to 85% complete response after second-round therapy prolongation to 12 months. Conclusions: Conservative measures must be considered temporary to allow pregnancy and subsequently perform specific counseling to adopt surgery. Fertility-sparing management is not the current standard of care for young women with EC. It can be employed for patients with early-stage diseases motivated to maintain reproductive function. Indeed, the results are encouraging, but the sample size must be increased

Leftovers:The presence of manufacture-derived aquatic lipids in Alaskan Pottery

Lipids preserved within the walls of ancient pottery vessels are routinely analysed to reveal their original contents. The provenience of aquatic lipids in pottery is generally connected to vessel function (e.g., for cooking or storing fish, shellfish and aquatic mammals). However, ethnographic reports from early historic Alaska mention the use of aquatic oils for waterproofing low-fired pottery. Results of lipid residue studies on Alaskan pottery reflect an exclusive function of pottery to process aquatic resources. However, can one be sure these residues are the product of vessel function and not a remnant of the manufacturing process? The study presents the results of an experiment where the preservation of aquatic lipids during the firing process at different temperatures was measured. It was found that nearly all lipids were removed at firing temperatures of ≥ 400°C. Petrographic analysis of Alaskan pottery samples indicates that firing temperatures were generally &gt; 550°C but &lt; 800°C. The contribution of pre-firing manufacture-derived lipids to samples fired at these temperatures may be regarded as negligible. While the possible presence of aquatic lipids from post-firing surface treatments cannot be excluded, such treatments appear unnecessary for well-fired pottery.</p