Lymphokine-induced phagocytosis in angiocentric immunoproliferative lesions (AIL) and malignant lymphoma arising in AIL

A factor that augmented the phagocytosis of IgG-coated ox red blood cells by the human monocyte/macrophage line U937 was identified in cell culture supernatants from two of two patients with angiocentric peripheral T cell lymphomas, three of three patients with angiocentric immunoproliferative lesions that were not frankly malignant, and one of two patients with T lymphoblastic malignancies. The factor was not present in supernatants derived from 14 nonangiocentric peripheral T cell lymphomas of other histologic types nor in ten cases of B cell lymphoma and two cases of Hodgkin's disease. A similar factor was present in the supernatants of concanavalin A (Con A)-stimulated normal peripheral blood mononuclear cells and in the supernatants of IL-2- dependent T cell lines derived from normal peripheral blood. The factor had an apparent mol wt of greater than 50,000 daltons, was heat labile (100 degrees C for two minutes), and stable at pH 2.0. Its stimulation of phagocytosis was independent of any increase in number of Fc receptors. Thus, this factor is probably not gamma-interferon. This factor may play a pathogenetic role in the hemophagocytic syndromes associated with certain T cell malignancies and immunodeficient states.     

Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma

CD19 chimeric antigen receptor T (CAR T)-cell therapy with axicabtagene ciloleucel (axi-cel) for relapsed or refractory (R/R) large B-cell lymphoma (LBCL) may lead to durable remissions, however, prolonged cytopenias and infections may occur. In this single center retrospective study of 85 patients, we characterized immune reconstitution and infections for patients remaining in remission after axi-cel for LBCL. Prolonged cytopenias (those occurring at or after day 30 following infusion) were common with ≥grade 3 neutropenia seen in 21 of 70 (30%) patients at day 30 and persisting in 3 of 31 (9.7%) patients at 1 year. B cells were undetectable in 30 of 34 (88.2%) patients at day 30, but were detected in 11 of 19 (57.9%) at 1 year. Median immunoglobulin G levels levels reached a nadir at day 180. By contrast, CD4 T cells decreased from baseline and were persistently low with a median CD4 count of 155 cells/mL at 1 year after axi-cel (n=19, range: 33– 269). In total, 23 of 85 (27.1%) patients received intravenous immunoglobulins after axi-cel, and 34 of 85 (40%) received granulocyte-colony stimulating factor. Infections in the first 30 days occurred in 31 of 85 (36.5%) patients, of which 11 of 85 (12.9%) required intravenous antibiotics or hospitalization (“severe”) and were associated with cytokine release syndrome, neurotoxicity, tocilizumab use, corticosteroid use, and bridging therapy on univariate analyses. After day 30, seven severe infections occurred, with no late deaths due to infection. Prolonged cytopenias are common following axi-cel therapy for LBCL and typically recover with time. Most patients experience profound and prolonged CD4 T-cell immunosuppression without severe infection.     

Role of copper in mitochondrial iron metabolism

Heme synthesis by copper-deficient cells was investigated to elucidate the nature of the defect in intracellular iron metabolism. Iron uptake from transferrin by copper-deficient reticulocytes was 52% of normal, and the rate of heme synthesis was 33% of normal. Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate. The rate of heme synthesis correlated with the cytochrome oxidase activity. Heme synthesis from Fe(III) and protoporphyrin by normal mitochondria was enhanced by succinate and inhibited by malonate, antimycin A, azide, and cyanide. It is proposed that an intact electron transport system is required for the reduction of Fe(III), thereby providing a pool of ferrous iron (Fe II) for protoheme and heme a synthesis.     

Familial aggregation of irritable bowel syndrome: a prospective study

BACKGROUND: Patients with irritable bowel syndrome (IBS) often report family members with similar symptoms, but family studies are lacking. We hypothesised that if there is familial aggregation, there would be an increased frequency of IBS in first degree relatives of IBS patients compared with relatives of controls (the patient's spouse). METHODS: A valid self report bowel disease questionnaire (BDQ) that recorded symptoms, the somatic symptom checklist (a measure of somatisation), and a family information form (FIF) to collect the names and addresses of all first degree relatives were mailed to two groups of patients and their spouses (patients attending an IBS educational programme and residents of Olmsted County, Minnesota, who had been coded as IBS on a database). A BDQ was then mailed to all first degree relatives of subjects identified from the FIF. IBS diagnosis in the relatives was based on the Manning criteria. RESULTS: The BDQ was sent to a total of 355 eligible relatives; 71% responded (73% relatives of patients, 67% relatives of spouses). Relatives were comparable in mean age, sex distribution, and somatisation score. IBS prevalence was 17% in patients' relatives versus 7% in spouses' relatives (odds ratio adjusted for age and sex 2.7 (95% confidence interval (CI) 1.2, 6.3)). When also adjusted for somatisation score, the odds ratio was reduced to 2.5 (95% CI 0.9, 6.7). CONCLUSIONS: Familial aggregation of IBS occurs, supporting a genetic or intrafamilial environment component, but this may be explained in part by familial aggregation of somatisation.     

A prospective study comparing radiographer- and clinician-based localization for patients with metastatic spinal cord compression (MSCC) to assess the feasibility of a radiographer-led service

Objective:

To investigate whether there was parity between treatment fields localized by radiographers and clinicians, by comparing geographical variations and hence determining the feasibility of a radiographer-led service.

Methods:

23 patients with metastatic spinal cord compression (MSCC) were prospectively sampled. Four radiographers not involved in the original planning performed localization on each patient. The 92 localizations that they determined were compared with the clinician-approved fields. Agreement was defined as ≤0.5 cm between field length, width and three isocentre co-ordinates. To be feasible, agreement was required in a minimum of 97% of the cases. The potential time saved with a radiographer-led approach was also recorded.

Results:

Agreement between clinicians and radiographers was 97.8%. For all field parameters, the average differences were <0.3 cm and were significantly different from the 0.5-cm median (p < 0.0001) that would establish no agreement using Wilcoxon signed-rank test. The average (range) delay awaiting clinician approval was 54 min (4–141 min).

Conclusion:

Strong agreement between radiographer and clinician localizations was established. It was also highlighted that time could be saved in the patient''s pathway by removing the need to wait for clinician approval. We believe this supports a radiographer-led service.

Advances in knowledge:

This article is novel, as it is the first known comparison between clinicians and radiographers in the localization of MSCC radiotherapy. These data show the feasibility of introducing radiographer-led practice and a methodology that could be potentially transferred to investigate the localization parity for other treatment sites.     

Changes in the site- and histology-specific incidence of gastric cancer during a 50-year period

In contrast to the dramatic decrease in the overall incidence of gastric cancer, there has been a reported increase in the incidence of cases located in the gastric cardia. The aim of this study was to identify changes in site- and histology-specific incidence rates of gastric adenocarcinoma during a 50-year period. The Rochester Epidemiology Project medical records linkage system was used to identify all cases of gastric adenocarcinoma among residents of Olmsted County, Minnesota, between 1941 and 1990 (n = 342). Each patient's complete (inpatient and outpatient) medical records were reviewed and tumor location determined from pathological, surgical, endoscopic, and radiological reports. All available histological specimens (n = 246) were reviewed independently. The overall incidence of gastric cancer decreased from 48.8 per 100,000 person-years in the 1940s to 11.6 per 100,000 in the 1980s, whereas the incidence of adenocarcinoma of the cardia did not change significantly during the 50-year period. The incidence of adenocarcinoma of the esophagogastric junction increased from 0.0 to 1.9 per 100,000 person-years, but the number of cases was small. The incidence of adenocarcinoma of the gastric cardia has not increased in this population. The reported increase in cardia cancer in other populations may be due to an increasing incidence of adenocarcinoma of the esophagogastric junction.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.     

A National Study of Outcomes among HIV-Infected Kidney Transplant Recipients

Kidney transplantation is a viable treatment for select patients with HIV and ESRD, but data are lacking regarding long-term outcomes and comparisons with appropriately matched HIV-negative patients. We analyzed data from the Scientific Registry of Transplant Recipients (SRTR; 2002–2011): 510 adult kidney transplant recipients with HIV (median follow-up, 3.8 years) matched 1:10 to HIV-negative controls. Compared with HIV-negative controls, HIV-infected recipients had significantly lower 5-year (75.3% versus 69.2%) and 10-year (54.4% versus 49.8%) post-transplant graft survival (GS) (hazard ratio [HR], 1.37; 95% confidence interval [95% CI], 1.15 to 1.64; P<0.001) that persisted when censoring for death (HR, 1.43; 95% CI, 1.12 to 1.84; P=0.005). However, compared with HIV-negative/hepatitis C virus (HCV)–negative controls, HIV monoinfected recipients had similar 5-year and 10-year GS, whereas HIV/HCV coinfected recipients had worse GS (5-year: 64.0% versus 52.0%, P=0.02; 10-year: 36.2% versus 27.0%, P=0.004 [HR, 1.38; 95% CI, 1.08 to 1.77; P=0.01]). Patient survival (PS) among HIV-infected recipients was 83.5% at 5 years and 51.6% at 10 years and was significantly lower than PS among HIV-negative controls (HR, 1.34; 95% CI, 1.08 to 1.68; P<0.01). However, PS was similar for HIV monoinfected recipients and HIV-negative/HCV-negative controls at both times. HIV/HCV coinfected recipients had worse PS compared with HIV-negative/HCV-infected controls (5-year: 67.0% versus 78.6%, P=0.007; 10-year: 29.3% versus 56.23%, P=0.002 [HR, 1.57; 95% CI, 1.11 to 2.22; P=0.01]). In conclusion, HIV-negative and HIV monoinfected kidney transplant recipients had similar GS and PS, whereas HIV/HCV coinfected recipients had worse outcomes. Although encouraging, these results suggest caution in transplanting coinfected patients.