Pubertal attainment and Leydig cell function following pediatric hematopoietic stem cell transplantation: a three-decade longitudinal assessment.

Introduction: Impaired testosterone secretion is a frequent sequela following hematopoietic stem cell transplantation (HSCT) in pediatrics, but long-term longitudinal trendlines of clinical and biochemical findings are still scanty. Methods: Monocentric, retrospective analysis. Male patients transplanted <18 years between 1992 and 2021, surviving ≥2 years after HSCT and showing, upon enrollment, clinical and biochemical signs consistent with pubertal onset and progression were included. Clinical and biochemical data collected every 6-12 months were recorded. Results: Of 130 patients enrolled, 56% were prepubertal, while 44% were peri-/postpubertal upon HSCT. Overall, 44% showed spontaneous progression into puberty and normal gonadal profile, while the remaining experienced pubertal arrest (1%), isolated increase of FSH (19%), compensated (23%) or overt (13%) hypergonadotropic hypogonadism. Post-pubertal testicular volume (TV) was statistically smaller among patients still pre-pubertal upon HSCT (p 0.049), whereas no differences were recorded in adult testosterone levels. LH and testosterone levels showed a specular trend between 20 and 30 years, as a progressive decrease in sexual steroids was associated with a compensatory increase of the luteinizing hormone. A variable degree of gonadal dysfunction was reported in 85%, 51%, 32% and 0% of patients following total body irradiation- (TBI), busulfan-, cyclophosphamide- and treosulfan-based regimens, respectively. TBI and busulfan cohorts were associated with the lowest probability of gonadal event-free course (p<0.0001), while it achieved 100% following treosulfan. A statistically greater gonadotoxicity was detected after busulfan than treosulfan (p 0.024). Chemo-only regimens were associated with statistically larger TV (p <0.001), higher testosterone (p 0.008) and lower gonadotropin levels (p <0.001) than TBI. Accordingly, the latter was associated with a 2-fold increase in the risk of gonadal failure compared to busulfan (OR 2.34, CI 1.08-8.40), whereas being pre-pubertal upon HSCT was associated with a reduced risk (OR 0.15, CI 0.08-0.30). Conclusions: a) patients pre-pubertal upon HSCT showed a reduced risk of testicular endocrine dysfunction, despite smaller adult TV; b) patients showed downwards trend in testosterone levels after full pubertal attainment, despite a compensatory increase in LH; c) treosulfan was associated to a statistically lower occurrence of hypogonadism than busulfan, with a trend towards larger TV, higher testosterone levels and lower gonadotropins.

Physicians and alternative medicines in "The Barber of Seville" by Gioachino Rossini: A bicentennial debate.

BACKGROUND: The year 2016 marks the bicentennial anniversary of the premiere of "The Barber of Seville" by Gioachino Rossini (1792-1868). This opera buffa, one of the most renowned in the world, puts on stage a sharp criticism against the physicians of that time in favour of empiric healers, respectively represented by the doctor Bartolo and the barber Figaro. METHODS: The paper analysed both the opera by Rossini and the French comedy "Le Barbier de Séville" (1775) by Pierre Beaumarchais (1732-1799), on which the Italian composer based his own play. RESULTS: The unlearned barber Figaro is portrayed as a poor but wise guy, while his rival, the graduated doctor Bartolo, is defined as an arrogant and opulent old physician. Dr. Bartolo's incompetence, lack of skill and ignorance are evident in the works by Rossini and Beaumarchais. Both plays show empiric and unskilled medicine triumphs over academic medicine, which appears weak in its scientific concepts and corrupted by money. CONCLUSIONS: Arrogance, presumption and carelessness among physicians are a danger nowadays as they have been for a couple of hundred years, since they may not only lead to misjudgement and errors, but also to an increase of alternative medicines and strange healing remedies.

The Neurologist in Dante's Inferno.

The year 2015 marks the 750th birth anniversary of the Italian poet Dante Alighieri (1265-1321). It is less known that Dante had a sound level of medical knowledge, probably derived by his academic studies. In his works, medieval notions of neuroanatomy and neurophysiology (e.g. the connection between brain and spinal cord, function of optic nerve and peripheral nerves, knowledge of vegetative nervous system) and descriptions of neurological disorders (e.g. epileptic seizures, effects on nervous system by metal intoxication, and narcolepsy) may be found, specially in the Inferno, the first part of his masterpiece, the Divine Comedy. These accurate descriptions have led some authors to believe that the poet himself may have suffered from a neurological disease (epilepsy or hypersomnia). Damned souls of the Inferno seem to be also afflicted by psychiatric disorders, such as melancholia and depression. The analysis of Dante's works confirms that poetry - as well as literature in general - may be an important source of information for historians of neurology.