Hypothyroxinemia in premature infants: is thyroxine treatment necessary?

The increased survival of very low birth weight (VLBW) premature infants has been associated with an increased prevalence of transient disorders of thyroid function during the early weeks of life. All VLBW infants have relatively low, and gestation age-dependent, thyroxine-binding globulin (TBG) concentrations associated with variably low total thyroxine (T4) concentrations. These infants also have a high prevalence (30%-60%) of nonthyroidal illnesses that impact thyroid function, including total and free iodothyronine concentrations. Finally, thyroid gland hormone biosynthesis and the hypothalamic-pituitary axis are relatively immature and thyroid glandular iodine stores are low. As a result, VLBW infants manifest a high prevalence of transient primary hypothyroidism (0.41%) and transient hypothalamic-pituitary (thyrotropin [TSH] deficiency) hypothyroidism (5%-10%?). Thyroid function should be monitored in VLBW infants during the first 1-4 weeks of life to detect these disorders as well as the much less common permanent congenital hypothyroidism. An elevated serum TSH level (> 20 mU/L) is diagnostic of primary hypothyroidism and a low free T4 concentration with a normal or low serum TSH level suggests hypothalamic-pituitary hypothyroidism. Treatment of transient or permanent primary hypothyroidism and of congenital TSH deficiency is indicated. Preliminary data suggests that 30-60-day treatment of transient hypothalamic-pituitary hypothyroidism improves IQ at 2 years of age. However, further information confirming the benefit of treatment, the threshold free T4 values for diagnosis, and the optimal dose of T4 are necessary.     

Minimal residual disease in chronic lymphocytic leukaemia: is it ready for primetime?

New therapeutic modalities have substantially improved response rates and outcomes in chronic lymphocytic leukaemia (CLL), yet the mindset remains that palliation is the only goal of therapy because the disease is considered incurable. Ultimately, all patients relapse despite achieving an initial response, as minimal residual disease (MRD) persisting after therapy eventually evolves into morphological and clinical recurrence. The emergence of immune-based combination therapies capable of inducing molecular remissions, the availability of highly sensitive assays that detect MRD, and emerging data showing a longer duration of response or longer survival in patients with no detectable disease, suggest that eradicating MRD may be a reasonable option for some patients. Moreover, novel biological prognostic markers have divided CLL into favourable and unfavourable subtypes, arguing in favour of defining different goals of therapy for different patients. Clinicians are increasingly challenged with the task of how best to incorporate MRD assessment into clinical practice, especially in an era when these novel prognostic factors exist. This review summarises the current understanding of MRD from a clinical standpoint, suggests that MRD eradication maybe a reasonable option for some patients, and argues in favour of designing large randomised studies to determine whether MRD-negative remission improves outcome.     

Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

Indocyanine green(ICG) kinetics(PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors(pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests.