Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 µg/24 h (193.1 nmol/L); (2) cortisol after 1‐mg dexamethasone suppression test (1‐mg DST) >3.0 µg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X‐ray absorptiometry and TBS was assessed in the region of LS‐BMD; BMD and TBS data were reported as Z‐scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n = 34) had lower LS‐BMD (?0.31 ± 1.17), FT‐BMD (?0.29 ± 0.91), and TBS (?3.18 ± 1.21) than patients without SH (n = 68, 0.31 ± 1.42, p = 0.03; 0.19 ± 0.97, p = 0.01; ?1.70 ± 1.54, p < 0.0001, respectively) and controls (0.42 ± 1.52, p = 0.02; 0.14 ± 0.76, p = 0.02; ?1.19 ± 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1‐mg DST (β = ?0.26, t = ?2.79, p = 0.006) regardless of age, LS‐BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85–12.42, p = 0.001) and with the cluster low TBS plus low LS‐BMD (OR, 4.37; 95% CI, 1.71–11.4, p = 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS‐BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > ?1.5) plus normal LS‐BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71–71.41, p = 0.012) regardless of LS‐BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures. © 2012 American Society for Bone and Mineral Research.     

Documento español de consenso sobre diagnóstico,estabilización y tratamiento del síndrome inflamatorio multisistémico pediátrico vinculado a SARS-CoV-2 (SIM-PedS)

A new paediatric multisystem inflammatory syndrome, linked to SARS-CoV-2, has been described. The clinical picture is variable and is associated with an active or recent infection due to SARS-CoV-2. A review of the existing literature by a multidisciplinary group of paediatric specialists is presented in this document. Later, they make recommendations on the stabilisation, diagnosis, and treatment of this syndrome.     

Genetic variations in host IL28B links to the detection of peripheral blood mononuclear cells–associated hepatitis C virus RNA in chronically infected patients

Hepatitis C virus (HCV) is mainly hepatotropic; however, several reports document the presence of genomic viral RNA in extrahepatic sites including peripheral blood mononuclear cells (PBMCs). In this study, the presence of HCV RNA was initially evaluated in the plasma and peripheral blood mononuclear cells (PBMCs) of 53 HCV‐infected patients who were treated per protocol. PBMC‐associated HCV RNA was detectable in 79% of patients. Early virological response to combined pegylated interferon‐α (PegIFN) and ribavirin (RBV) therapy in patients with undetectable levels of PBMCs‐associated HCV RNA was 100%, while it was 60% (P = 0.003) in those who had detectable levels of PBMC‐associated HCV RNA. A sustained virological response was observed in 35% of patients with detectable PBMC‐associated HCV RNA, but was 70% in patients with undetectable levels of PBMC‐associated HCV RNA (P = 0.07). In a multivariate analysis incorporating parameters such as HCV genotype, viral load, presence of cirrhosis and absence of PBMC‐associated HCV RNA, a significant relationship was observed between the detection of PBMC‐associated HCV RNA and the sustained virological response (OR 19.4, 95% CI: 2.1–486.2, P = 0.0061). The association between single nucleotide polymorphism (SNP) in IL28B, known predictor of antiviral therapy outcome, and the occurrence of HCV RNA in PBMC in 84 chronically infected patients was then evaluated. Results suggest that the presence of a G allele in rs8099917, known to associate to a poor response to PegIFN/RBV therapy, also predicts an increased association of HCV RNA with PBMC (OR: 3.564; 95% CI: 1.114–11.40, P = 0.0437).     

Bladder transitional cell carcinoma and BK virus in a young kidney transplant recipient

Kidney transplant recipients have a heightened risk of developing neoplasms. Immunosuppressive treatments decrease the incidence of transplant rejection but increase the risk of infections, including BK virus (BKV). This infection is acquired in childhood and remains latent in the renal and urinary epithelium. In cases of immunodeficiency, BKV has been implicated as a tumor virus, but the role of BKV in cancer is a controversial topic and is difficult to determine. In the tumor cells, it is possible to detect fragments of the viral genome that could alter the control mechanisms of the cell cycle and DNA repair. We report the case of a kidney transplant recipient who developed BKV nephropathy and carcinoma of the bladder, supporting a possible role for BKV in the oncogenic pathway in this clinical setting, but the role of BKV in cancer remains a controversial topic and difficult to determine.     

The Toxicity of Repeated Exposures to Rolipram,a Type IV Phosphodiesterase Inhibitor,in Rats

Abstract: Rolipram is a selective inhibitor of Type IV phosphodiesterase isozymes (PDE IV) which is often used as a baseline comparator for compounds in this class. To document the toxicological effects of rolipram, it was administered to female rats at 0, 10, 30 or 100 mg/kg/day orally for up to 2 weeks. One treatment-related death in the 100 mg/kg/day dose group was observed on day 3, and all rats at this dose level were considered moribund and euthanatized on day 5. Several clinical signs were observed in treated rats, including increased salivation, slight distention of the abdomen, emaciated appearance, and ataxia. After 14 days of treatment, the rats were necropsied and tissues examined microscopically. A number of compound-related histopathological changes were observed in rats receiving 30 or 100 mg/kg/day. Myocardial degeneration and necrosis, endocardial fibrosis, epicarditis, and arteritis/periarteritis of intramural and extramural coronary arteries were observed in the heart. A necrotizing vasculitis and inflammation were observed in the mesentery and interstitial areas of the liver, affecting medium-sized portal arteries and veins. Focal necrosis was also observed in the glandular mucosa of the stomach at these 2 dose levels. Other treatment-related effects included squamous hyperplasia and hyperkeratosis with or without ulceration in the nonglandular stomach of at least one animal from all treatment groups. Enlarged salivary glands were noted at necropsy in animals treated with 100 mg/kg/day, and this finding correlated microscopically with dilatation and degeneration of ducts and acini in the sublingual gland with secondary inflammation and edema. The results of this study demonstrate that rolipram, a selective inhibitor of the type IV class of PDE, can cause effects on the heart and vasculature of rats which heretofore have been ascribed only to selective inhibitors of the PDE III class of isozymes. Therefore, these organs should be closely examined in studies with other PDE IV inhibitors. In addition, the gastrointestinal tract and salivary glands were sites for rolipram-induced toxicity and may be targets of other PDE IV inhibitors.     

A double-blind controlled trial of recombinant interferon-α2b in haemodialysis patients with chronic hepatitis C virus infection and abnormal aminotransferase levels

SUMMARY. The efficacy and safety of recombinant interferon-α2b (rIFN-α2b) was evaluated in a double-blind controlled trial comprising 23 haemodialysis patients with antibodies to hepatitis C virus (anti-HCV), detectable serum HCV RNA by polymerase chain reaction and chronic alanine aminotransferase elevation. The patients were randomly assigned to receive rIFN-α2b at a dose of 1.5 MU (increasing to 3 MU if no response was observed) (Group I: n = 14) or identical placebo (Group II: n = 9), for 6 months. A biochemical response (normal alanine aminotransferase) was observed in 10 patients (71.4%) from Group I and in one patient (11.1%) from Group II (P < 0.01) at the end of therapy, and in four patients from Group I (28.6%) and in none from Group II (NS) 12 months after therapy. Virological response (HCV RNA negative) was observed in four patients (28.6%) from Group I and in none from Group II (NS) at the end of therapy, and in two patients (14.2%) from Group I and in none from Group LT (NS) 12 months after therapy. Interferon doses were 1.5 MU in 12 patients and 3 MU in two patients. Therapy interruption owing to severe side-effects was necessary in three patients (21.4%) from Group I and in two patients (22.2%) from Group II. Although long-term statistical differences were not observed, these results suggest that rIFN-α2b at a low dose is a reasonable and well tolerated therapeutic approach for haemodialysis patients with chronic hepatitis C.     

Role of free vascularized bone grafts in the experimentally-induced ischemic necrosis of the femoral head.

In 15 mongrel adult dogs, an ischemic necrosis of the femoral head was produced, following the technique described by Gartsman and colleagues. Five weeks later, a 6- to 8-cm long rib graft was harvested with its vascular bundle and transferred into the previously induced ischemic femoral head. Microsurgical anastomoses were performed for revascularizing the rib graft. Dogs were studied using scintigraphy, blood flow measurements, roentgenograms, angiograms, and histology at four, eight and 12 weeks after grafting. New bone and vascular formation was exhibited throughout the study, as demonstrated by a highly positive scintigraphic activity and the formation of numerous arterial terminal branches arising from the rib graft circulation which entered the femoral head and reached the subchondral plate. The formerly necrotic femoral head bone exhibited osteoblastic activity, viable osteocytes, and well-populated bone marrow. The rib graft was also incorporated into the femoral head. These results suggest that a vascularized bone graft is able to repair a femoral head necrosis, and may be considered a rational approach for clinical purposes.     

Local control and reduced complications in split course irradiation of prostatic cancer

Split course prostatic irradiation is a treatment technique where 4000–4500 rod whole pelvis irradiation is followed by two weeks of rest and an additional 2000–2500 rod by reduced field technique to a total dose of 6000–6500 rod. Eighty-four patients were studied and the results indicated a local regional control rate of 97.6% with an overall 3 year survival without evidence of disease of 96.6% for Stages A and B and 60% for Stage c. Significant complications occurred in 1.2 % of the patients. None of the patients needed surgical correction of a complication other than a perineal abscess. The risk/benefit ratio for pelvic and prostatic irradiation favors split course prostatic irradiation in that it demonstrates a low complication rate, high local regional control, and comparable disease-free survival to continuous irradiation.     

Ultrasound examination in ovarian cancer patients. A comparison with second look laparotomy

A series of 129 patients with International Federation of Gynecology and Obstetrics (FIGO) stage III-IV ovarian cancer, were evaluated with ultrasound examination and second look surgery. Results of both modalities were correlated in order to assess the reliability of ultrasound in detecting residual disease. After six cycles of chemotherapy, ultrasound was negative in 94 patients and positive in 35 patients. At second look, 57 patients were in complete pathologic remission, 16 had microscopic residual disease, 23 had macroscopic disease less than 2 cm, and 33 had macroscopic disease greater than 2 cm. Correlating ultrasonography and laparotomy, high correlations were seen in patients with no residual disease (92.2%); on the other hand, ultrasound examinations exhibited poor sensitivity and specificity in patients with microscopic disease (6.2%) and residual disease less than 2 cm (8.6%). Using ultrasound discrimination among patients with no residual disease, microscopic disease, or macroscopic disease less than 2 cm does not appear possible. Our suggestion is that ultrasound is not able to replace second look laparotomy in the detection of minimal residual disease in ovarian cancer patients.