Klinefelter syndrome and TESE-ICSI

Until few years ago, Klinefelter syndrome with a homogenous 47,XXY karyotype was considered a model of absolute male sterility. We will discuss first the potential fertility following Testicular Sperm Injection, then the physiopathology of spermatogenic failure and the origin of focal spermatogenesis and risk of aneuploidy in offspring, and third the advantage of searching spermatozoa earlier instead of adult age. The rate of positive sperm extraction seems to be better for younger patients. During childhood, there is a low rate of spermatogonia. The spermagonia, which completes the spermatogenesis, seems resulting from a rare clone of 46,XY gonia, having lost their extra X chromosome. Several arguments suggest that this focal spermatogenesis decreases with age. In addition, androgen treatment, frequently prescribed in case of Klinefelter syndrome, carries a risk of decreasing focal spermatogenesis by lowering gonadotropins. The question arises if it is necessary to expect the sperm cryopreservation before introducing androgen treatment. Further studies are necessary to determine the best age of sperm retrieval in case of Klinefelter syndrome.     

Synthesis and biological evaluation of heteroalicyclic cyanoguanidines at histamine receptors

Recent studies on histamine receptor (HR) subtypes identified imidazolyl butyl cyanoguanidines, like UR‐PI376, as highly potent agonists at the human histamine H₄ receptor (hH₄R). While imidazole‐containing compounds display drawbacks in pharmacokinetics, we studied the possibility of replacing the heteroaromatic cycle by nonaromatic six‐membered heterocycles (piperidine, morpholine, thiomorpholine, and N‐methylpiperazine) as potential bioisosteres. Beyond that, this approach should give more information about the indispensability of the aromatic ring as a basic head group. Besides these changes, a variation of the spacer length (C₃–C₅) connecting the heterocycle and the cyanoguanidine moiety has been made to possibly trigger the selectivity towards the respective HRs. Investigations in radioligand‐binding assays exhibited only very weak activity at the hH₁R and hH₃R, while nearly all compounds were inactive at the hH₂R and hH₄R. In the case of piperidine‐containing compounds, moderate affinities at the hH₃R over the single‐digit micromolar range were detected.     

Prognosis and health-related quality of life in elderly patients after a mild to moderate trauma

The aims of this study were to compare outcome after a mild to moderate trauma in three subgroups of patients of increasing age (A1: <50, A2: 50–74, A3: >74 years) and to assess potential health-related quality of life (HRQOL) impairment. This is a follow-up study of a cohort of 418 trauma patients admitted to the High Dependency Unit of the Emergency Department of the University Hospital of Florence from July 2008 to February 2012. Six months after the event, a telephone interview using the Physical component summary (PCS) and Mental component summary (MCS) Health Composite Score (SF12) was conducted. Patients reported their QOL both at present and before trauma. In-hospital mortality was 10 of 418 (2.3 %); overall mortality was 27 of 244 (11 %) patients found at follow-up. No death was observed among A1 patients; overall mortality was (6/76) 7 % in A2 and (21/71) 30 % in A3 patients (p < 0.05 A1 vs A2, A1 vs A3 and A2 vs A3). Before the event, respectively, 94 and 96 % patients reported a normal MCS and PCS score (>39); after the event, the proportion of patients with a normal score value was significantly lower (MCS 70 %, p = 0.002; PCS 58 %, p < 0.0001). All subgroups showed a highly significant reduction in the scores’ value due to the trauma. After the event, the proportion of patients with normal scores was significantly lower (all p < 0.0001, except for MCS score in A1 subgroup, who showed p = 0.013) within all subgroups. Elderly patients’ prognosis was significantly worse compared with the younger counterpart; despite young patients’ optimal outcome, HRQOL was uniformly reduced across all age groups.     

Prior antiplatelet drug use and short-term mortality in older patients with acute ischemic stroke (AIS)

Some studies suggest that previous treatment with antiplatelet agents (AA) might reduce ischemic stroke severity and improve outcomes in terms of clinical deficits or mortality. We evaluated the effect of the prior chronic use of AA on short-term (30 days) mortality in a sample of consecutive patients with AIS. Four hundred thirty-nine older patients (>65 years) with “major” AIS (modified Rankin scale ≥ 3) consecutively admitted to the University ward of Internal Medicine or Geriatrics were enrolled. Stroke was classified according to Oxfordshire Community Stroke Project (OCSP). Data recorded included: (1) clinical features; (2) medical history including home therapies, and vascular risk factors; (3) routine clinical chemistry analyzes (verb)/analyses (noun). Short-term (30 days) mortality was 27.6%. One hundred fifteen subjects (26.2%) were taking AA before admission. Compared with subjects not treated, subjects taking AA were characterized by higher prevalence of recurrent stroke (35% vs. 22%). In this group, a trend toward a higher prevalence of congestive heart failure (CHF), smoking, and altered levels of consciousness (ALC) was noted. Stroke type and short-term mortality (33% vs. 26.2%; odds ratio = OR = 1.25; 95% confidence interval = CI = 0.75-2.10, age and gender adjusted) were not different between the two groups. Adjustment for glucose, CHF, previous stroke, smoking, and ALC did not change mortality risk (OR = 0.83; 95%CI = 0.40-1.72). We conclude that in older patients hospitalized for “major” AIS, prior use of AA was not associated with any benefit in terms of short-term mortality both in patients with first, as well as in those with recurrent ischemic stroke.     

Midregional pro-A-type natriuretic peptide for diagnosis and prognosis in patients with suspected acute myocardial infarction

We hypothesized that midregional pro-A-type natriuretic peptide (MR-proANP), the stable midregional epitope of proANP, might be useful in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction (AMI). In this multicenter study we measured MR-proANP, cardiac troponin T (cTnT), and high-sensitive cTnT (hs-cTnT) at presentation in 675 consecutive patients presenting to the emergency department with suspected AMI. The final diagnosis was adjudicated by 2 independent cardiologists. Patients were followed 360 days for mortality and AMI. AMI was the final diagnosis in 119 patients (18%). Median MR-proANP levels at presentation were significantly higher in patients with AMI (189 pmol/L, interquartile range 97 to 341) versus patients with another final diagnosis (83 pmol/L, 49 to 144, p <0.001). However, neither the combination of MR-proANP with cTnT nor its combination with hs-cTnT significantly improved diagnostic accuracy as quantified by area under the receiver operating characteristic curve (0.91 vs 0.89 for cTnT alone, p = 0.086; 0.95 vs 0.96 for hs-cTnT, respectively, p = 0.02). Cumulative 360-day mortality/AMI rates were 2.4% in the first, 3.6% in the second, 9.5% in the third, and 18.8% in the fourth quartiles of MR-proANP (p <0.001). MR-proANP (area under the curve 0.76) predicted mortality/AMI independently of and more accurately than cTnT (area under the curve 0.62), hs-cTnT (area under the curve 0.71), and Thrombolysis In Myocardial Infarction risk score (area under the curve 0.72). Net reclassification improvements offered by the additional use of MR-proANP were 0.388 (p <0.001), 0.425 (p <0.001), and 0.217 (p = 0.007), respectively. In conclusion, MR-proANP improves risk prediction for 360-day mortality/AMI but does not seem to help in the early diagnosis of AMI.