Non-GH Agents and Novel Therapeutics in the Management of Short Stature

Short stature is one of the most common reasons for referral to pediatric endocrinologists. The vast majority of short children do not have growth hormone (GH) deficiency or another pathologic process that is interfering with normal growth. While GH has been approved in the US for several etiologies of non-GH deficient short stature, its high cost and need for daily injections represent barriers for many families. Alternative agents for the management of short stature include the use of gonadotropin releasing hormone analogs (GnRHas) to delay puberty, and aromatase inhibitors (AIs) in boys to postpone epiphyseal fusion. The results of studies employing GnRHas as either monotherapy or combined with GH are mixed, and there is a dearth of rigorously designed clinical trials that have followed patients to adult height. While AIs have been found to result in modest increases in adult height in some studies, important questions about their long-term safety exist. The C-type natriuretic peptide analog vosoritide is an experimental agent that is emerging as a potential treatment for a few specific conditions including achondroplasia, although its efficacy in attenuating disproportionality is as yet unproven. While each of these therapeutic strategies holds promise, none are currently considered standard of care and several important questions remain. These include the impact of these interventions on quality of life as well as long-term outcomes

Tumoral CD105 is a novel independent prognostic marker for prognosis in clear-cell renal cell carcinoma

International audienceBackground: Angiogenesis is essential for tumour growth and metastasis. There are conflicting reports as to whether microvessel density (MVD) using the endothelial marker CD105 (cluster of differentiation molecule 105) in clear-cell renal cell carcinomas (ccRCC) is associated with prognosis. Recently, CD105 has been described as a RCC cancer stem cell marker.Methods: A total of 102 ccRCC were analysed. Representative tumour sections were stained for CD105. Vascularity (endothelial CD105) was quantified by MVD. The immunohistochemistry analysis detected positive (if present) or negative (if absent) CD105 tumoral staining. This retrospective population-based study was evaluated using Kaplan–Meier method, t-test and Cox proportional hazard model.Results: We found that the expression of endothelial CD105 (MVD) negatively correlated with nuclear grade (P<0.001), tumour stage (P<0.001) and Leibovitch score (P<0.001), whereas the expression of tumoral CD105 positively correlated with these three clinicopathological factors (P<0.001). In multivariate analysis, tumoral CD105 was found to be an independent predictor of poor overall survival (P=0.002).Conclusions: We have shown for the first time that tumoral CD105 is an independent predictive marker for death risk and unfavourable prognosis in patients with ccRCC after curative resection

The history of leishmaniasis

In this review article the history of leishmaniasis is discussed regarding the origin of the genus Leishmania in the Mesozoic era and its subsequent geographical distribution, initial evidence of the disease in ancient times, first accounts of the infection in the Middle Ages, and the discovery of Leishmania parasites as causative agents of leishmaniasis in modern times. With respect to the origin and dispersal of Leishmania parasites, the three currently debated hypotheses (Palaearctic, Neotropical and supercontinental origin, respectively) are presented. Ancient documents and paleoparasitological data indicate that leishmaniasis was already widespread in antiquity. Identification of Leishmania parasites as etiological agents and sand flies as the transmission vectors of leishmaniasis started at the beginning of the 20th century and the discovery of new Leishmania and sand fly species continued well into the 21st century. Lately, the Syrian civil war and refugee crises have shown that leishmaniasis epidemics can happen any time in conflict areas and neighbouring regions where the disease was previously endemic

LBSAT311 Rhabdomyolysis: A Rare Presentation Of Hashimoto Thyroiditis In An Adolescent Boy

Introduction: Hashimoto thyroiditis is the most common cause of hypothyroidism and is associated with a wide range of clinical presentations in children and adolescents. Hypothyroidism-induced rhabdomyolysis without precipitating factors is extremely rare, particularly in pediatric patients. We describe a previously healthy adolescent boy who came to our institution with vague symptoms and was found to have rhabdomyolysis secondary to hypothyroidism due to Hashimoto thyroiditis. Clinical Case: A 16 year old boy presented to the emergency department at Riley Hospital for Children due to a two week history of bilateral eye and lip swelling. Additional symptoms included fatigue, sleepiness, slowing of speech, decreased attention span and weight gain. He was not on any medications and had no history of allergies. There was no family history of endocrine or neuromuscular disorders. Physical exam revealed a height of 177 cm (75th tile), weight of 118.4 kg (99th %tile) and BMI at the 99th %tile. Exam was significant for slow generalized movements, facial edema, and delayed deep tendon reflexes in all extremities. The thyroid gland was normal. Laboratory evaluation revealed Creatinine-1.46 mg/dL (0.3-1.2), ALT-88 Units/L (7-52), AST-254 Units/L (13-39), TSH-32.2 mcU/mL (0.4-4.2), fT4 <0.2 ng/dL (0.6-1.5) and CK 20,500 Units/L (30-223). Thyroid peroxidase antibody was elevated at 686.1 IU/mL. A renal and bladder ultrasound showed trace intra-abdominal ascites and decreased echogenicity of the bilateral psoas muscles favoring edema and consistent with rhabdomyolysis. He received IV hydration and was started on levothyroxine 25 mcg daily that was increased over a 10 month period to achieve euthyroidism. Genetic testing for rhabdomyolysis revealed two variants of unknown significance. Acyl carnitine and carnitine profiles were normal ruling out a metabolic myopathy. His symptoms improved significantly after treatment with levothyroxine although his CK levels plateaued around 1,000 Units/L. Liver and kidney function normalized during follow up. Conclusion: Rhabdomyolysis is a rare but serious complication of hypothyroidism, the pathogenesis of which is unclear. Proposed hypotheses include impaired mitochondrial oxidative metabolism, decreased muscle carnitine and switching of muscle fibers from fast-twitching type II to slow-twitching type I due to thyroxine deficiency ultimately leading to myolysis and release of intracellular muscle contents into the circulation. It is important for clinicians to have a high index of suspicion for hypothyroidism in children who present with muscle weakness and high creatinine kinase levels. The etiology of the disproportionately mild elevation of TSH in the setting of an unmeasurable free T4 and severe clinical hypothyroidism in our patient remains a mystery

A Standardized Set of 380 Pictures for Lebanese Arabic: Norms for Name Agreement, Conceptual Familiarity, Imageability, and Subjective Frequency.

peer reviewedResearch on language processing requires language-specific norms of pictorial and linguistic experimental stimuli across different psycholinguistic variables. Such normative data have not yet been collected for Lebanese Arabic (LA), an Arabic dialect. Arabic languages are characterized by diglossia: while modern standard Arabic is their common means of formal communication, Arabic dialects are the medium of oral communication within each community. This claims for specific dialectal norms. Thus, the main goal of the present study was to collect normative LA data for 380 pictures taken from Cykowicz, Friedman, Rothstein, and Snodgrass (The Quarterly Journal of Experimental Psychology Section A 50(3):560-585; including the 260 pictures of Snodgrass & Vanderwart in Journal of experimental psychology: Human learning and memory 6(2):174-215, 1980) using a sample of 248 native LA speakers. Norms are reported for name agreement, conceptual familiarity, imageability and subjective frequency, together with word length in number of letters and syllables. We compared the obtained norms with the normative data of other Arabic dialects (Levantine, Tunisian and Gulf Arabic) and with English, French and Spanish. Results showed the distinction of LA from the other Arabic dialects. This provides support of specific dialectal Arabic norms and will allow researchers to rigorously select the stimuli to investigate language processing in LA-speaking populations

A Comprehensive Literature Review and Expert Consensus Statement on Therapeutic Drug Monitoring of Biologics in Inflammatory Bowel Disease

Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease (IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1 to 10 (1=strongly disagree and 10=strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine and reformulate statements that did not meet criteria for agreement, or that were ambiguous. During the meeting, additional statements were proposed. Panellists then confidentially re-voted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded; 7 new statements were proposed; and 19 statements were rerated. Consensus was finally reached in 48/49 statements. The panel agreed that reactive TDM should be utilized for all biologics for both primary non-response and secondary loss of response. It was recommended that treatment discontinuation should not be considered for infliximab or adalimumab until a drug concentration of at least 10-15μg/ml was achieved. Consensus was also achieved regarding the utility of proactive TDM for anti-tumor necrosis factor (anti-TNF) therapy. It was recommended to perform proactive TDM post-induction and at least once during maintenance. Consensus was achieved in most cases regarding the utility of TDM of biologics in IBD, specifically for reactive and proactive TDM of anti-TNFs