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Summary: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral overproduction of FGF-23. Due to local recurrence, we describe the long-term efficacy and safety profile of burosumab, an anti-FGF-23 monoclonal antibody, in a TIO patient after three unsuccessfully surgical attempts. Introduction: TIO is a rare paraneoplastic syndrome caused by tumoral overproduction of fibroblast growth factor 23 (FGF23), resulting in hyperphospaturia, hypophosphatemia, and osteomalacia. Surgery is the only definitive treatment, but tumor can locally recur, even after years from primary surgery. Furthermore, some tumors cannot be removed by surgery due to their location. Methods: We describe the case of a 54-year-old woman affected by recurrent TIO who, after three unsuccessful surgical attempts of tumor removal, was treated with burosumab, an anti-FGF-23 monoclonal antibody. Results: The patient was referred to our Bone Unit after experiencing several fractures in different sites, both traumatic and non-traumatic. At the time of first evaluation, at the age of 46, serum-phosphate (SP) was 1.2 mg/dL (reference range (RR) 2.5–4.5), 24-h urinary phosphate was 842 mg (RR 400–1000), and intact-FGF-23 was 117 pg/mL (RR 25–45). Imaging showed a metabolic pre-sacral lesion that firstly underwent to exploratory laparotomy. Then, patient underwent to surgical excision of tumor. After 18 months of well-being, tumor relapsed and even the subsequent surgery was not able to completely remove it. Since 2015, patient was maintained in phosphorus supplements and 1,25(OH)2vitamin D3, but SP levels never normalized. In September 2019, she was started on burosumab, initially at the dose of 0.3 mg/kg/month, progressively increased to the current 0.8 mg/kg/month, with great improvement of pain, physical performance, and normalization of SP levels. Burosumab was temporary and cautionary discontinued for COVID-19 pneumonia, with a worsening of SP. After restart of burosumab, biochemistry returned to normal. Conclusions: To our knowledge, this is the first European patient affected by TIO treated with burosumab for more than 2 years. Burosumab is a promising therapy in the medical treatment of TIO refractory or not eligible for definitive surgery, with good efficacy and safety profile. [ABSTRACT FROM AUTHOR]

Sickle Cell Anaemia (SCA) is the most common inherited blood disorder and is associated with severe morbidity and decreased survival. Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) is the only curative approach. Nevertheless the decision to perform a bone marrow transplant includes the risk of major complications and transplant-related mortality. Infections represent the leading cause of death in SCA patients undergoing HSCT. Invasive Pulmonary Aspergillosis (IPA) is a devastating opportunistic infection and remains a significant cause of morbidity and mortality in HSCT recipients. Data regarding IPA in the setting of SCA are lacking. In the present report, we describe a patient with SCA, who developed IPA after allogeneic bone marrow transplant. The fungal infection was treated by systemic antifungal therapy in addition to surgery, despite mild chronic graft versus host disease (GVHD) and continuing immunosuppressive therapy. This case shows that IPA occurring in bone marrow recipients with SCA can be successfully treated. C [ABSTRACT FROM AUTHOR]

We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2-4 and 3-4 aGVHD was 35% (95% confidence interval (CI) 25-44) and 9% (95% CI 4-16), respectively. We found that CD3+ and CD34+ cell doses above the median were associated with high incidence of grade 2-4 aGVHD (49 vs 20%, P=0.005 and 46 vs 23%, P=0.021, respectively). In multivariate analysis, high CD3+ (hazard ratio (HR) 4.6; 95% CI 1.4-14.7; P=0.010) and CD34+ (HR 4.3; 95% CI 1.4-12.7; P=0.011) cell doses were associated with grade 2-4 aGVHD. We further examined the effect of CD3+ and CD34+ cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3+ (38 × 106/kg) and CD34+ (4 × 106/kg) cells above which the incidence of grade 2-4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3+ and CD34+ cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD. [ABSTRACT FROM AUTHOR]

As part of prevention of HIV mother-to-child transmission (PMTCT) strategies, HIV-positive women are asked to choose between two options regarding infant feeding: replacement feeding or exclusive breastfeeding with early weaning. Health services must offer women counseling, guidance, and support to enable them to make an informed choice. This article aims to shed light on the content of counseling and its adaptation to local situations, including women's perceptions, in three resource-poor countries with different infant feeding patterns (Burkina Faso, Cambodia, and Cameroon). The qualitative study included observations in health facilities and interviews with HIV-positive mothers and health workers. The results show that counseling practices vary, including prescriptive counseling proposing only one option to all women, an option based on the mother's economic level assessed by health care providers, and the choice between options. While health workers consider economic aspects first, women mostly consider social aspects related to the risk of being stigmatized as a 'bad mother'' or as HIV-positive. Overall trends identify some limits to counseling effectiveness when considering women's perceptions and needs, such as: the content of information provided by health care providers, duration and timing of counseling, discrepancies between information provided during counseling and from the health system, and ranking of preventive options by health workers. Women's agency for feeding choices is related to local practices and local authorities' abilities to provide more or less comprehensive counseling based on the organization of the health and aid system. Local practices also depend on institutions' interpretations of international recommendations based on public health considerations regarding standard of care and women's and the health system's respective responsibilities. Beyond structural constraints that hinder the adoption of preventive infant feeding patterns, addressing these issues may help improve counseling practices. [ABSTRACT FROM AUTHOR]

Demonstrates the expression of Epstein-Barr virus (EBV) transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. Includes case report; Methods; Results; Discussion.

Abstract: The objectives of the present work were (1) to study the effects of complexity and intensity of foods on sensory specific satiety (SSS) and their acceptance after repeated consumption, and (2) to determine the predictive value of SSS for acceptance over repeated consumption. Two studies were performed: a soup study (N =66) and a snack study (N =61). In the snack study, the intense snacks produced somewhat more SSS than the less intense snacks (F(3,177)=2.2, p =0.09). Both studies demonstrated that pleasantness of stimuli with a near to optimal arousal level, which is a combination of complexity and intensity, was more resistant to a decline over repeated exposure than of stimuli with lower arousal levels (soups: F(14,546)=2.0, p =0.04; snacks: F(15,450)=6.1, p =0.003). The data do not support the idea that SSS could serve as a rapid predictor of long-term acceptance (soups: r SSS-repeated consumption =−0.05, p =0.73; snacks: r SSS-repeated consumption =0.20, p =0.19). These findings need to be confirmed with stimuli that are more comparable with respect to initial liking and sensory qualities other than intensity and complexity. [Copyright &y& Elsevier]