Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance?

We identified 68 patients with clonal T-large granular lymphocyte (T- LGL) proliferations who were seen at the Mayo Clinic between 1984 and 1992. Nineteen (28%) were asymptomatic at diagnosis, while the rest experienced fatigue (60%), B-symptoms (12%), and recurrent infections (15%). Associated comorbid conditions included rheumatoid arthritis (RA) in 26%. Severe anemia (hemoglobin [Hb] < 8g/dL) and neutopenia (absolute neutrophil count [ANC] < 500/microL) were seen in 19% and 40% of patients, respectively. Immunophenotypic studies showed CD3+, CD8+ phenotype in the majority (72%). Twenty-one patients (31%) have required no therapy, and remain relatively stable with a median follow- up period of 50 months. Treatment was required at either diagnosis (36 patients) or at subsequent follow-up (11 patients). Initial response rates were similar in patients treated with cyclophosphamide (CTX) with or without prednisone (69%), or prednisone alone (73%). Overall, 61 patients (90%) are alive with a median follow-up of 44 months. Actuarial median survival of this entire cohort is 161 months. The presence of anemia or symptoms does not appear to correlate with the tumor burden. In patients requiring therapy, a lower ANC and the presence of B-symptoms/infection were independently associated with a significantly lower probability of achieving a molecular or hematologic complete remission (H-CR). Intermittent immunosuppressive therapy is effective in achieving durable responses in a number of patients. T-LGL proliferations are associated with a favorable prognosis and response to therapy. However, significant heterogeneity exists in clinical presentation and associated comorbid conditions. These disorders should be included in the differential diagnosis of patients with unexplained cytopenias, particularly in the setting of RA and other autoimmune disorders. Analogous to the situation with monoclonal gammopathies, a term such as T-cell clonopathy of undetermined significance (TCUS) may be more appropriate to describe these patients.     

Effects of Prenatal Nicotine Exposure on Infant Language Development: A Cohort Follow Up Study

Objectives To study the longitudinal effects of prenatal nicotine exposure on cognitive development, taking into consideration prenatal and postnatal second-hand smoke exposure. Methods A cohort follow up study was carried out. One hundred and fifty-eight pregnant women and their infants were followed during pregnancy and infant development (at 6, 12, 30 months). In each trimester of pregnancy and during postnatal follow-up, a survey was administered to obtain sociodemographic data and the details of maternal and close familial toxic habits. Obstetric and neonatal data were obtained from hospital medical records. To assess cognitive development, the Bayley Scales of Infant Development were applied at 6, 12 and 30 months; to assess language development, the MacArthur-Bates Communicative Development Inventories were applied at 12 months and the Peabody Picture Vocabulary Test at 30 months. Results After adjustment for confounding variables, the results showed that infants prenatally exposed to cigarette smoke recorded poor cognitive development scores. Language development was most consistently affected, specifically those aspects related to auditory function (vocalizations, sound discrimination, word imitation, prelinguistic vocalizations, and word and sentence comprehension). Conclusions for Practice Irrespective of prenatal, perinatal and sociodemographic data (including infant postnatal nicotine exposure), prenatal exposure to cigarette smoke and second-hand smoke affect infant cognitive development, especially language abilities.     

Risk of high‐level viraemia in HIV‐infected patients on successful antiretroviral treatment for more than 6 months

Objectives

According to the Swiss Federal Commission for HIV/AIDS, HIV‐infected patients on successful antiretroviral treatment have a negligible risk of transmitting HIV sexually. We estimated the risk that patients considered to have an undetectable viral load (VL) are actually viraemic.

Methods

A Danish, population‐based nationwide cohort study of HIV‐infected patients with VL <51 HIV‐1 RNA copies/mL for more than 6 months was carried out for the study period 2000–2008. The observation time was calculated from 6 months after the first VL <51 copies/mL to the last measurement of VL or the first VL >50 copies/mL. The time at risk of transmitting HIV sexually was calculated as 50% of the time from the last VL <51 copies/mL to the subsequent VL if it was >1000 copies/mL. The outcome was the time at risk of transmitting HIV sexually divided by the observation time.

Results

We identified 2680 study subjects contributing 9347.7 years of observation time and 56.4 years of risk of transmitting HIV (VL>1000 copies/mL). In 0.6% [95% confidence interval (CI) 0.5–0.8%] of the overall observation time the patients had VL >1000 copies/mL. In the first 6 months this risk was substantially higher (7.9%; 95% CI 4.5–11.0%), but thereafter decreased and was almost negligible after 5 years (0.03%; 95% CI 0.0–0.2%). The risk was higher in injecting drug users, but otherwise did not differ between subgroups of patients.

Conclusion

The risk of viraemia and therefore the risk of transmitting HIV sexually are high in the first 12 months of successful antiretroviral treatment, but thereafter are low.     

Soft tissue management of children's open tibial fractures �C a review of seventy children over twenty years

INTRODUCTION

The management of open tibial fractures in children represents a unique reconstructive challenge. The aim of the study was to evaluate the management of paediatric open tibial fractures with particular regard to soft tissue management.

PATIENTS AND METHODS

A retrospective case-note analysis was performed for all children presenting with an open tibial fracture at a single institution over a 20-year period for 1985 to 2005.

RESULTS

Seventy children were reviewed of whom 41 were males and 29 females. Overall, 91% (n = 64) of children suffered their injury as a result of a vehicle-related injury. The severity of the fracture with respect to the Gustilo classification was: Grade I, 42% (n = 29); Grade II, 24% (n = 17); Grade III, 34% (n = 24; 7 Grade 3a, 16 Grade 3b, 1 Grade 3c). The majority of children were treated with external fixation and conservative measures, with a mean hospital in-patient stay of 13.3 days. Soft tissue cover was provided by plastic surgeons in 31% of all cases. Four cases of superficial wound infection occurred (6%), one case of osteomyelitis and one case of flap failure. The limb salvage was greater than 98%.

CONCLUSIONS

In this series, complications were associated with delayed involvement of plastic surgeons. Retrospective analysis has shown a decreased incidence of open tibial fractures which is reported in similar studies. Gustilo grade was found to correlate with length of hospital admission and plastic surgery intervention. We advocate, when feasible, the use of local fas-ciocutaneous flaps (such as distally based fasciocutaneous and adipofascial flaps), which showed a low complication rate in children.     

Association of maternal protein intake before conception and throughout pregnancy with birth weight

BACKGROUND: The aim of this study is to analyze how the maternal intake of macronutrients before conception and in the 6th, 10th, 26th, and 38th weeks of pregnancy affects birth weight. METHODS: A longitudinal study of food consumption to assess the nutritional status of 77 healthy female volunteers (age range: 24-36) who were planning immediate pregnancy was performed in Reus between 1992 and 1996. A seven-consecutive-day dietary record was used in order to evaluate the dietary intake. We fitted multiple linear regression models of macronutrients on birth weight adjusted for energy intake, maternal age, pre-conceptional body mass index, sex of the newborn, length of pregnancy, parity, physical activity in leisure time, and smoking. RESULTS: In the 6th, 10th, and 26th weeks of pregnancy, 7.2-12.7% of the variability of the birth weight can be explained by the intake of macronutrients. In the protein and fat model, a 1 g increase in maternal protein intake during preconception and in the 10th, 26th, and 38th weeks of pregnancy leads to a significant increase of 7.8-11.4 g in birth weight. CONCLUSIONS: The diet of well-nourished women in the preconception period and throughout most of pregnancy has a significant effect on birth weight, and proteins are the macronutrient that has the greatest influence.     

Hepcidin levels and gastric cancer risk in the EPIC‐EurGast study

Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case‐control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow‐up. We measured serum levels of hepcidin‐25, iron, ferritin, transferrin and C‐reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin‐gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93–0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: ?69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis.