The problem of infections in acute leukemias

Summary This report is based on experience over the last 5 years in the diagnosis and treatment of infections in 200 acute leukemic patients hospitalized in the Institute of Haematology, University of Rome. The relevant clinical and laboratory findings are discussed in relation to the diagnosis of secondary infections. Most of the febrile episodes were associated with infection. The frequently rapid development of the infections in these patients requires empirical antibiotic treatment. The best results were obtained when the combinations carbenicillin-cephalothin-gentamicin (success rate of 65 %), and carbenicillin-cephalothin-gentamicin-lyncomycin-methicillin (success rate of 62 %), were used as empirical therapy.     

Intraoperative radiotherapy during radical prostatectomy for intermediate‐risk to locally advanced prostate cancer: treatment technique and evaluation of perioperative and functional outcome vs standard radical prostatectomy,in a matched‐pair analysis

OBJECTIVE

To evaluate a novel approach with intraoperative radiotherapy (IORT) administered in the surgical field, after pelvic lymphadenectomy (PL) and before radical retropubic prostatectomy (RRP), evaluating acute and late toxicity, complications and biochemical progression‐free survival (bPFS), as the adequate treatment of locally advanced prostate cancer is still a controversial issue.

PATIENTS AND METHODS

Between June 2005 and October 2007, 33 consecutive patients with intermediate‐risk or locally advanced prostate cancer were selected for PL + IORT + RRP. IORT was delivered by a mobile linear accelerator in the operating room (electron beam, 12 Gy at 90% isodose). According to the pathological findings further adjuvant radio‐ or hormone therapy could be administered. The median follow‐up was 16 months. This group was compared retrospectively with a historical group of 100 patients who had undergone RRP and further adjuvant therapy, selected with equivalent criteria. The comparison was conducted as a matched‐pair analysis. The perioperative outcomes (surgical time, estimated blood loss, blood transfusions, days of catheterization, days of drainage, days of hospitalization), continence as the functional outcome, acute and late toxicity, rate of complications and bPFS were evaluated and compared.

RESULTS

The baseline characteristics of the two groups were equivalent but the node count and the number of positive lymph nodes was higher in the IORT group. The IORT group had longer surgery, and a shorter hospital stay and catheterization. There were no differences in continence rate, and no major complications in either group. The acute and late toxicity and bPFS were equivalent. A retrospective comparison and the short follow‐up were the major limitations.

CONCLUSIONS

IORT administered before RRP seems a feasible approach, with little effect on the variables evaluated.     

Effect of laser therapy (660 nm) on recovery of the sciatic nerve in rats after injury through neurotmesis followed by epineural anastomosis

The aim of this study was to analyze the influence of aluminum gallium arsenide (AlGaAs) laser (660 nm) on the myelin sheath and functional recovery of the sciatic nerve in rats. The sciatic nerves of 12 Wistar rats were subjected to injury through neurotmesis and epineural anastomosis, and the animals were divided into two groups: group 1 was the control and group 2, underwent low-level laser therapy (LLLT). After the injury, AlGaAs laser at 660 nm, 4 J/cm², 26.3 mW and beam area of 0.63 cm² was administered to three equidistant points on the injury for 20 consecutive days. In the control group the mean area of the myelin impairment was 0.51 (± 0.11) on day 21 after the operation, whereas this value was 1.31 (± 0.22) in the LLLT group. Student’s t-test revealed a P value = 0.0229 for the mean area values of the myelin sheath between the LLLT and control groups. Comparison of the sciatic functional index (SFI) showed that there was no significant difference between the pre-lesion value in the laser therapy group and the control group. The use of AlGaAs laser (660 nm) provided significant changes to the morphometrically assessed area of the myelin sheath, but it did not culminate in positive results for functional recovery in the sciatic nerve of the rats after injury through neurotmesis.     

The Effect of a Silybin-Vitamin E-Phospholipid Complex on Nonalcoholic Fatty Liver Disease: A Pilot Study

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-β, tumor necrosis factor-α, degree of steatosis, and γ-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage. Other members of the Real Sud Group: L. Cimino, Federico II University, Naples; V. De Girolamo and A. Marone, Ascalesi Hospital, Naples; C. De Stefano, S. Carlo Hospital, Potenza; G. De Stefano, Madonna delle Grazie Hospital, Matera; D. Disalvo and B. Provenzano, Villa D’Agri Hospital, Potenza; P. Esposito and A. Simonetti, Second University, Naples; M. D. Iannece and R. Pempinello, Cotugno Hospital, Naples; R. Iorio, Giugliano Hospital, Naples; S. Monastra and M. Di Pierro, S. Gennaro Hospital, Naples.     

Pathologic Determinants of Survival After Resection of T3N0 (Stage IIA) Colorectal Cancer: Proposal for a New Prognostic Model

Purpose There is an increasing need for accurate prognostic stratification of patients with Stage II colorectal cancer to identify a subgroup of high-risk patients who may benefit from adjuvant therapies. This study was designed to evaluate the prognostic impact of a wide spectrum of pathologic parameters in a consecutive series of homogenously treated and well-characterized patients with Stage IIA (T3N0M0) colorectal cancer. Methods The study included 238 patients operated on by a single surgeon for Stage IIA colorectal tumors. The median postoperative follow-up was 110 (range, 96–120) months. At least 12 lymph nodes were harvested and examined in all the resection specimens. The prognostic value of 13 pathologic parameters, including lymph node occult disease (micrometastases) detected by immunohistochemistry, was investigated. Results Multivariate analysis identified tumor growth pattern (expanding or infiltrating; P = 0.01) and extent of tumor spread beyond muscularis propria (≤5 mm or >5 mm; P = 0.04) as the only factors having independent prognostic value. The combination of these two easily determined parameters allowed us to identify two groups of patients at low risk or high risk of tumor recurrence. The eight-year survival rates were 83.3 and 53.4 percent for the two groups, respectively. The high-risk group comprised those patients with infiltrating tumors and extramural tumor spread > 5 mm. Conclusions We propose a new and simple prognostic model to identify patients with high-risk Stage IIA colorectal cancer for whom adjuvant therapies may be justified and effective. Supported by grants from the Italian Ministry of University, Scientific and Technological Research, the Ente Cassa di Risparmio di Firenze, and the Associazione Italiana Ricerca sul Cancro.     

Effect of Hypoxia and Aging on PKC δ‐Mediated SC‐35 Phosphorylation in Rat Myocardial Tissue

Nuclear speckles, which are sites of pre‐mRNA splicing and/or assembly components, are diffusely distributed throughout the nucleoplasm. They are composed of splicing factors (SFs), including SC‐35, which are nuclear proteins that remove introns (noncoding sequences in the genes) from precursor mRNA molecules, to form mature RNA, which will be transported to the cytoplasm, site of protein synthesis and activation. In light of such evidences, here we report that hypoxia modulates in vivo SC‐35 SF phosphorylation via protein kinase C (PKC) δ in young rat heart. Trichrome Mallory staining and TUNEL analysis along with immunohistochemistry and Western blotting have been performed on left ventricles excised from young and old rats exposed to intermittent hypoxia. Although young hypoxic myocardial cells appear smaller than normoxic cells, connective and endothelial components increase, SC‐35 phosphorylation is particularly evident in the endothelium and paralleled by an increased expression of vascular endothelial growth factor (VEGF). In addition, SC‐35 and PKC δ coimmunoprecipitation occurs, suggesting that SC‐35 phosphorylation could be PKC δ‐mediated and that hypoxic young heart needs to counteract the damage through a process of neoangiogenesis involving such SF. Even though the levels of SC‐35 and PKC δ are high, the similar response disclosed by normoxic and hypoxic old rat hearts (both showing a fibrotic organization, similar endothelial components and VEGF levels) could be due to the existence of an impaired oxygen sensing mechanism and thus to a low rate of angiogenesis. Anat Rec, 292:1135–1142, 2009. © 2009 Wiley‐Liss, Inc.     

Atrial septal defect closure and migraine with aura: is there a correlation?

Recently, some authors detected increased frequency or new onset of migraine with aura (MA) after atrial septal defect (ASD) closure. We report the effects of ASD closure on the occurrence of MA in three patients of Parma Headache Centre. Two of them developed MA after the procedure one had a worsening of pre-existing MA. The increased frequency or the de novo onset of MA after ASD closure may be related to the alteration of some physiological variables that play a central role in the physiopathogenetic mechanisms of MA and may trigger attacks in predisposed individuals. In previous literature reports, the new pattern of MA appeared self-limiting within a few weeks or months. In our cases, it seemed to last longer, but the natural history of this headache subtype suggests that this finding could be related to the extended duration of our follow-up and to the prospective nature of our study.     

Restoration of hypoglycemia awareness after islet transplantation

OBJECTIVE—To determine the impact of islet transplantation (ITx) on hypoglycemia awareness in patients with unstable type 1 diabetes and its relation to islet function.RESEARCH DESIGN AND METHODS—A total of 31 ITx recipients were studied. Hypoglycemia unawareness was assessed using the Clarke hypoglycemic score (0 = no hypoglycemia; ≥4 = hypoglycemia unawareness). Subjects were grouped based on graft function: off-insulin (n = 8), graft dysfunction (on-insulin and stimulated C-peptide ≥0.3 ng/ml, n = 13), and graft failure (stimulated C-peptide <0.3 ng/ml, n = 10, evaluated 11.5 ± 14.5 months after graft failure).RESULTS—The hypoglycemia score improved after ITx when compared with baseline values (before vs. after: 5.29 ± 1.51 vs. 1.35 ± 1.92, P < 0.001). This result was sustained even after patient stratification based on islet function (pre vs. post off-insulin: 5.63 ± 2.00 vs. no hypoglycemia reported; graft dysfunction: 5.31 ± 1.49 vs. 1.15 ± 1.63, P < 0.001; and graft failure: 5.00 ± 1.16 vs. 2.70 ± 2.26, P = 0.014).CONCLUSIONS—The improved metabolic control achieved with ITx can restore hypoglycemia awareness in patients with type 1 diabetes, persisting even after islet graft failure.Occurrence of hypoglycemia is the major limitation of intensive control aimed at A1C normalization in patients with type 1 diabetes. Frequent hypoglycemic episodes are particularly common in subjects with unstable type 1 diabetes and can lead to hypoglycemia unawareness. Although islet transplantation (ITx) prevents severe hypoglycemia (1) and restores some counterregulatory hormone secretion (2), data showing its effects on restitution of hypoglycemia awareness are not conclusive (2,3).The aim of this study was to determine if the optimal metabolic control achieved by ITx can restore hypoglycemia awareness and whether or not these effects persist after islet graft failure.