Increasing incidence of melanoma after solid organ transplantation: a retrospective epidemiological study

The risk of melanoma in organ transplant recipients (OTR) is increased compared with the general population. This retrospective study registered all cases of post‐transplant melanoma in kidney, heart, lung, and liver transplant recipients followed in our specialized post‐transplant Dermatology Clinic since 1991. The yearly prevalence of melanoma and skin carcinoma between 2000 and 2015 was computed and compared in this population. Based on another cohort of kidney transplant recipients grafted since 2005, adjusted age‐ and sex‐standardized incidence ratio (SIR) was calculated using a renal transplantation registry. In our overall OTR cohort, between 1991 and 2000, five melanomas occurred in 1800 OTRs (0.28%), whereas between 1991 and 2015, 53 melanomas were diagnosed in 49 of 4510 OTR (1.09%), representing a 3.9‐fold increase in prevalence after 2000. Remarkably, the prevalence of nonmelanoma skin cancers remained unchanged over this period. Two deaths related to melanoma were recorded with an overall follow‐up of 62 months. In our cohort of 1102 renal transplant recipients, the SIR of melanoma was 4.52. Our data suggest that contrasting with nonmelanoma skin cancer, the risk of post‐transplant melanoma has considerably increased over the last decade.     

Latent tuberculosis in a newborn: diagnostic challenges

In countries where the incidence of tuberculosis is low, perinatal tuberculosis is seldom diagnosed. With increasing numbers of human immunodeficiency virus-infected people and increasing immigrant population from high tuberculosis incidence countries, one might expect perinatal tuberculosis to become more frequent. Early recognition of newborns at risk for perinatal tuberculosis infection is of utmost importance to prevent disease by chemoprophylaxis. We describe a case of latent perinatal tuberculosis infection in a newborn infected from a mother with extrapulmonary primary tuberculosis. Tuberculin skin test was negative, and latent tuberculosis infection was eventually diagnosed by specific immunological tests. We discuss the difficulties in diagnosis of recent tuberculosis infection in neonates and infants, and the risk factors for vertical transmission of tuberculosis, which need to be taken into account in considering the need for chemoprophylaxis in the newborn. Although perinatal TB infection is a rare condition and diagnosis is difficult due to poor diagnostic testing in pregnancy and newborns, a high index of suspicion is needed to limit the diagnostic delay and to avoid progression to perinatal TB disease.     

Overcoming acquired resistance to letrozole by targeting the PI3K/AKT/mTOR pathway in breast cancer cell clones

Development of resistance to endocrine therapy is a clinical issue in estrogen receptor (ER)-positive breast cancer. Here we show that persistent activation of AKT/mTOR signaling is crucial to the acquisition of letrozole resistance in cell clones generated from MCF-7/AROM-1 aromatase-expressing breast cancer cells after prolonged letrozole exposure. ERα plays a marginal role in this context. As a proof of concept, the association between PI3K/AKT/mTOR signaling and insensitivity to endocrine therapies was confirmed in breast cancer patients who developed early letrozole resistance in neoadjuvant setting. In addition our results suggest that, regardless of the mechanism mediating the activation of AKT/mTOR pathway, either RAD001 or NVP-BEZ235 treatment may represent a promising strategy to overcome acquired resistance to letrozole in breast cancers dependent on AKT/mTOR signaling.     

Simultaneous 3-dimensional resolution correction in SPECT reconstruction with an ordered-subsets expectation maximization algorithm

Collimators are used for the improvement of information about the positions of sources by limiting the incidence direction of gamma-rays and characteristic x-rays to detectors. In this study, we attempted to improve the spatial resolution of (201)Tl myocardial SPECT by using simultaneous 3-dimensional distance-dependent resolution correction (DRC) incorporated into the ordered-subsets expectation maximization algorithm. METHODS: Simulation was performed with various sizes of balls, and measurement with a line-source phantom was performed at different source-detector distances. Imaging of a hot-rod phantom, the defect area of a myocardial phantom, and the myocardial thickness and cardiac lumen in a human study by (201)TlCl myocardial SPECT was evaluated before and after DRC. RESULTS: We performed simulation by using 5 sizes of balls and found marked improvement in resolution in all x-, y-, and z-axis directions. In the line-source phantom, when the radial distance was very long (30.5 cm), the correction effects were slightly low. However, when the distance was similar to the clinically used rotation radius (22.5 cm), the correction effects were good in the hot-rod and myocardial phantoms and in the human study. CONCLUSION: DRC markedly improved the spatial resolution of SPECT images, suggesting that this method is useful for the quantification of infarcted areas by myocardial SPECT.     

Utilization patterns,outcomes and costs of a simplified acute malnutrition treatment programme in Burkina Faso

Access to treatment for acute malnutrition remains a challenge, in part due to the fragmentation of treatment programmes based on case severity. This paper evaluates utilization patterns, outcomes and associated costs for treating acute malnutrition cases among a cohort of children in Burkina Faso. This study is a secondary analysis of a proof‐of‐concept trial, called Optimizing treatment for acute Malnutrition (OptiMA), conducted in Burkina Faso in 2016. A total of 4958 eligible children whose mid‐upper arm circumference (MUAC) was less than 125 mm or with oedema were followed weekly and given ready‐to‐use therapeutic foods (RUTF). We evaluated the service utilization and outcomes among patients and estimated resource use and variable cost per patient, and examined factors driving variation in resource use. Children with lower initial MUAC level grew faster but required more time to recover than those with higher initial MUAC level. They also had higher rates of death, default and nonresponse. The simplified OptiMA approach for treating acute malnutrition achieved high rates of recovery overall (84%), especially among less severe cases, with modest quantities of RUTF. The average overall variable cost per child admitted was US$38.0 (SD: 20.5) half of which was accounted for by the cost of RUTF. Cost per recovered case was correlated with case severity, ranging from US$35.1 to US$132.8. If simplified integrated programmes using severity‐based RUTF dosing can increase access to treatment at earlier, less severe stages of acute malnutrition, they can help avoid more serious and costlier cases.