Adverse effects of intrathecal methotrexate in children with acute leukemia in remission

A toxic syndrome characterized by fever, headache, and vomiting, lasting 2-5 days, occurred in 61% of 39 children with acute leukemia in complete remission, receiving central nervous system prophylaxis with intrathecal methotrexate, and in 14% of 34 children receiving the same plus cranial radiation. The syndrome was accompanied by pleocytosis with lymphocytes, monocytoid cells, and neutrophils. There was evidence of cumulative Mtx toxicity, since the toxic syndrome occurred mostly after the third and fourth dose and did not recur with longer intervals between doses. The incidence of the syndrome was significantly reduced by the use of Elliott's B solution as Mtx diluent, rather than water or normal saline. The occurrence of pleocytosis and toxic clinical syndrome was also significantly reduced in patients receiving concomitant cranial radiation, probably due to the lympholytic action of radiotherapy and the depressed cellular response of irradiated tissues. The use of Elliott's B solution as diluent for IT Mtx and an appropriate interval between Mtx doses are suggested for prevention of this toxic syndrome.     

Psychometric characteristics of the mutuality scale in heart failure patients and caregivers

Background

Higher patient-caregiver mutuality is associated with improved patient and caregiver outcomes, but no studies have tested the psychometric characteristics of the mutuality scale (MS) in heart failure (HF) patient and caregiver population.

ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn’s disease patients

AIM:To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease(CD).METHODS:In this study,we assessed the differential responses in phagocytosis by measuring the phagocytic activity and the percentage of active phagocytic monocytes and granulocytes in inflammatory bowel disease patients as well as healthy controls.As both autophagy related like 1(ATG16L1)and immunityrelated guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleo-tide-binding ligomerization domain-containing protein2(NOD2)has been identified as a potent inducer of autophagy we genotyped the patients for these variants and correlated this to the phagocytic reaction.The genotyping was done with restriction fragment length polymorphisms analysis and the phagocytosis was determined with the pHrodo?Escherichia coli Bioparticles Phagocytosis kit for flowcytometry.RESULTS:In this study,we demonstrate that analysis of the monocyte and granulocyte populations of patients with CD and ulcerative colitis showed a comparable phagocytic activity(ratio of mean fluorescence intensity)between the patient groups and the healthy controls.CD patients show a significantly higher phagocytic capacity(ratio mean percentage of phagocytic cells)compared to healthy controls(51.91%±2.85%vs 37.67%±7.06%,P=0.05).The extend of disease was not of influence.However,variants of ATG16L1(WT:2.03±0.19 vs homozygoot variant:4.38±0.37,P<0.009)as well as NOD2(C-ins)(heterozygous variant:42.08±2.94 vs homozygous variant:75.58±4.34(P=0.05)are associated with the phagocytic activity in patients with CD.CONCLUSION:Monocytes of CD patients show enhanced phagocytosis associated with the presence of ATG16L1 and NOD2 variants.This could be part of the pathophysiological mechanism resulting in the disease.     

Bowel endometriosis: Colorectal surgeon’s perspective in a multidisciplinary surgical team

Endometriosis is a gynecological condition that presents as endometrial-like tissue outside the uterus and induces a chronic inflammatory reaction. Up to 15% of women in their reproductive period are affected by this condition. Deep endometriosis is defined as endometriosis located more than 5 mm beneath the peritoneal surface. This type of endometriosis is mostly found on the uterosacral ligaments, inside the rectovaginal septum or vagina, in the rectosigmoid area, ovarian fossa, pelvic peritoneum, ureters, and bladder, causing a distortion of the pelvic anatomy. The frequency of bowel endometriosis is unknown, but in cases of bowel infiltration, about 90% are localized on the sigmoid colon or the rectum. Colorectal involvement results in alterations of bowel habits such as constipation, diarrhea, tenesmus, dyschezia, and, rarely, rectal bleeding. Differential diagnosis must be made in case of irritable bowel syndrome, solitary rectal ulcer syndrome, and a rectal tumor. A precise diagnosis about the presence, location, and extent of endometriosis is necessary to plan surgical treatment. Multidisciplinary laparoscopic treatment has become the standard of care. Depending on the size of the lesion and site of involvement, full-thickness disc excision or bowel resection needs to be performed by an experienced colorectal surgeon. Long-term outcomes, following bowel resection for severe endometriosis, regarding pain and recurrence rate are good with a pregnancy rate of 50%.     

Correlation of blood counts with vascular complications in essential thrombocythemia: analysis of the prospective PT1 cohort

Essential thrombocythemia, a myeloproliferative neoplasm, is associated with increased platelet count and risk of thrombosis or hemorrhage. Cytoreductive therapy aims to normalize platelet counts despite there being only a minimal association between platelet count and complication rates. Evidence is increasing for a correlation between WBC count and thrombosis, but prospective data are lacking. In the present study, we investigated the relationship between vascular complications and 21 887 longitudinal blood counts in a prospective, multicenter cohort of 776 essential thrombocythemia patients. After correction for confounding variables, no association was seen between blood counts at diagnosis and future complications. However, platelet count outside of the normal range during follow-up was associated with an immediate risk of major hemorrhage (P = .0005) but not thrombosis (P = .7). Elevated WBC count during follow-up was correlated with thrombosis (P = .05) and major hemorrhage (P = .01). These data imply that the aim of cytoreduction in essential thrombocythemia should be to keep the platelet count, and arguably the WBC count, within the normal range. This study is registered at the International Standard Randomized Controlled Trials Number Registry (www.isrctn.org) as number 72251782.