Computed Tomography in the Nontraumatic Renal Causes of Acute Flank Pain

Renal colic pain due to obstructing stone is the main renal cause of acute flank pain. However, other causes may be responsible for the same clinical findings, including acute pyelonephritis, acute vascular conditions, and hemorrhage. The purpose of this review is to describe the differential diagnosis, the computed tomographic findings and pitfalls, and the role and impact of computed tomography in the diagnosis and management of the renal causes of acute flank pain.     

Hemophagocytic syndrome as a presenting sign of transformation of smoldering to acute adult T-cell leukemia/lymphoma: efficacy of anti-retroviral and interferon therapy

A 55-year-old Caribbean woman with a 6-year history of smoldering adult T-cell leukemia/lymphoma presented with clinical and biological symptoms of hemophagocytic syndrome. An extensive search for infectious diseases was negative. A lymph node biopsy showing large T-cell lymphoma (CD4-, CD25+) and findings of high LDH count and severe lymphocytosis led to the diagnosis of acute adult T-cell leukemia/lymphoma. Anti-retroviral therapy combining zidovudine, lamivudine, and interferon-alpha was started, resulting in rapid control of both hemophagocytic syndrome and symptoms of acute adult T-cell leukemia/lymphoma. Thus, we propose that adult T-cell leukemia/lymphoma must be added to the spectrum of etiologies of hemophagocytic syndrome.     

Catheter ablation therapy for atrial fibrillation

Since cases were first reported in 1994, catheter ablation of atrial fibrillation has undergone rapid development and expansion. The procedure began as an attempt to recreate the Maze III operation with a catheter technique. Understanding the contribution of the pulmonary veins to the initiation and maintenance of atrial fibrillation led to dramatic changes in procedural technique. The segmental ostial and the circumferential approaches have emerged as the 2 dominant methods. Efforts continue in academic centers to better understand the pathophysiology of the arrhythmia and to further refine the ablation procedure to improve patient outcomes.     

Impact of hepatitis C virus recombinant form RF1_2k/1b on treatment outcomes within the Georgian national hepatitis C elimination program

Aim

Hepatitis C virus (HCV) recombinant form RF1_2k/1b is common in ethnic Georgians. This chimera virus contains genomic fragments of genotype 2 and genotype 1 and is misclassified as genotype 2 by standard genotyping. We aimed to identify RF1_2k/1b strains among genotype 2 patients and assess its impact on treatment outcomes.

Methods

The study included 148 patients with HCV genotype 2 as determined by 5‐untranslated region/core genotyping assay. RF1_2k/1b was identified by sequencing the non‐structural protein 5B region. Patients were treated within the national hepatitis C elimination program with sofosbuvir/ribavirin (SOF/RBV), interferon (IFN)/SOF/RBV, or ledipasvir (LDV)/SOF/RBV.

Results

Of 148 patients, 103 (69.5%) had RF1_ 2k/1b. Sustained virologic response (SVR) data was available for 136 patients (RF1_ 2k/1b, n = 103; genotype 2, n = 33). Sustained virologic response was achieved in more genotype 2 patient than in RF1_2k/1b patients (97.0% vs. 76.7%, P = 0.009). Twelve weeks of LDV/SOF/RBV treatment was highly effective (100% SVR) in both genotypes. Among RF1_2k/1b patients, LDV/SOF/RBV for 12 weeks was superior (100% SVR) to SOF/RBV for 12 weeks (56.4%, P < 0.0001) or 20 weeks (79.2%, P = 0.05). Twelve weeks of IFN/SOF/RBV also showed better response than SOF/RBV for 12 weeks (88.9% vs. 56.4%, P = 0.02) in these patients.

Conclusions

High prevalence of the RF1_2k/1b strain can significantly affect treatment outcomes. Treatment with IFN/SOF/RBV and especially LDV/SOF/RBV ensured significantly higher SVR in patients infected with RF1_2k/1b strain compared to standard HCV genotype 2 treatment with SOF/RBV. There is a need to reassess existing methods for the management of HCV genotype 2 infections, especially in areas with high prevalence of the RF1_2k/1b strain.     

Distinct roles of Mdm2 and Mdm4 in red cell production

Mdm2 and Mdm4 are critical negative regulators of the p53 tumor suppressor. Mdm4-null mutants are severely anemic and exhibit impaired proliferation of the fetal liver erythroid lineage cells. This phenotype may indicate a cell-intrinsic function of Mdm4 in erythropoiesis. In contrast, red blood cell count was nearly normal in mice engineered to express low levels of Mdm2, suggesting that Mdm2 might be dispensable for red cell production. Here, we further explore the tissue-specific functions of Mdm2 and Mdm4 in the erythroid lineage by intercrossing conditional Mdm4 and Mdm2 alleles to an erythroid-specific Cre (Er-GFP-Cre) knock-in allele. Our data show that Mdm2 is required for rescuing erythroid progenitors from p53-mediated apoptosis during primitive erythropoiesis. In contrast, Mdm4 is only required for the high erythropoietic rate during embryonic definitive erythropoiesis. Thus, in this particular cellular context, Mdm4 only contributes to p53 regulation at a specific phase of the differentiation program.     

Motor vehicle crash fatalities: A comparison of Hispanic and non-Hispanic motorists in Colorado

STUDY OBJECTIVES: We compare the population-based death rates from traffic crashes in the Hispanic and non-Hispanic white populations in a single state, and compare fatally injured Hispanic and non-Hispanic drivers with respect to safety belt use, alcohol involvement, speeding, vehicle age, valid licensure, and urban-rural location. METHODS: Hispanic and non-Hispanic white motorists killed in traffic crashes in 1991-1995 were studied (n=2,272). Data from death certificates (age, sex, education, race, and ethnicity) and the Fatality Analysis Reporting System (FARS; driver, vehicle, and crash information) were merged. Average annual age-adjusted fatality rates were calculated; to compare Hispanic and non-Hispanic white motorists, rate ratios (RR) and 95% confidence intervals (CIs) were calculated. Odds ratios (ORs), adjusted for age, sex, and rural locale, were calculated to measure the association between Hispanic ethnicity and driver and crash characteristics. RESULTS: Eighty-five percent of FARS records were matched to death certificates. Compared with non-Hispanic white motorists, Hispanics had higher crash-related fatality rates overall (RR 1.75, 95% CI 1.60 to 1.92) and for drivers only (RR 1.62, 95% CI 1.41 to 1.85). After adjustment for age, sex, and rural locale, Hispanic drivers had higher rates of safety belt nonuse (OR 1.81, 95% CI 1.20 to 2.72), legal alcohol intoxication (OR 2.73, 95% CI 1.97 to 3.79), speeding (OR 1.36, 95% CI 0.99 to 1.88), and invalid licensure (OR 2.58, 95% CI 1.78 to 3.75). The average vehicle age for Hispanic drivers (10.1 years, 95% CI 9.3 to 11.0) was greater than for non-Hispanic white motorists (8.8 years, 95% CI 8.4 to 9.2). CONCLUSION: Compared with non-Hispanic whites, Hispanic drivers have higher rates of safety belt nonuse, speeding, invalid licensure and alcohol involvement, with correspondingly higher rates of death in traffic crashes. As traffic safety emerges as a public health priority in Hispanic communities, these data may help in developing appropriate and culturally sensitive interventions.     

Severe decrease in peripheral blood dendritic cells in hairy cell leukaemia

Clinical studies in hairy cell leukaemia (HCL) have linked the frequent occurrence of infections due to intracellular pathogens and a profound monocytopenia. More recently, dendritic cells (DC), a subset of which are related to monocytes, were shown to be the professional antigen-presenting cells which stimulate the adaptive immune response. Using membrane markers and flow cytometry, we determined in peripheral blood whether various DC subsets and monocytes were impaired in HCL. Lymphoid and myeloid DC were virtually absent in five HCL patients with active disease. After treatment, both DC and monocytes recovered slowly. The decrease in DC suggests that defective antigen presentation could affect susceptibility to intracellular pathogens in HCL.     

Survival and specific outcome of sickle cell disease patients after renal transplantation

The prognosis of sickle cell disease (SCD) patients who need dialysis is poor, but experience with kidney transplantation is limited. This study assessed the characteristics of 36 SCD patients undergoing renal transplantation. Immediate post-surgical complications occurred in 25% of cases. Cytomegalovirus and bacterial infections were frequently observed. Twelve patients died after a median follow-up period of 17·4 months. Overall patient survival was significantly lower in SCD than in the control group without significant difference for overall death-censored graft survival. Our data suggest that renal transplantation should be systematically considered in SCD patients with end-stage renal disease.     

Increased risk of lipoatrophy under stavudine in HIV-1-infected patients: results of a substudy from a comparative trial

OBJECTIVES: To compare the incidence of clinical lipodystrophy in HIV-1-infected patients receiving zidovudine or stavudine, in combination with indinavir and lamivudine, in a randomized trial. METHODS: NOVAVIR was a randomized multicentre trial comparing stavudine/lamivudine/indinavir and zidovudine/lamivudine/indinavir in 170 patients pretreated with zidovudine, didanosine or zalcitabine (> 6 months), but naive for lamivudine, stavudine and protease inhibitors. The incidence of clinical lipodystrophy and metabolic abnormalities was assessed in a subgroup of 101 patients after 30 months of follow-up. RESULTS: The incidence of lipoatrophy was increased in the stavudine arm versus the zidovudine arm, as followed: facial atrophy: 48 versus 22% of patients, P = 0.011, lower limb atrophy: 49 versus 22% of patients, P = 0.006, buttock atrophy: 47 versus 20% of patients, P = 0.009, venomegaly: 57 versus 24% of patients, P = 0.001. There was no significant difference in the incidence of clinical signs of central fat accumulation nor in fasting metabolic parameters at month 30 between the two arms. In multivariate analyses, the stavudine arm, previous therapy with didanosine, and a lower CD4 cell count at study entry were associated with an increased risk of lipoatrophy, whereas older patients and women had an increased risk of lipohypertrophy. CONCLUSION: Patients receiving stavudine/lamivudine/indinavir had a greater rate of clinical lipodystrophy, mainly lipoatrophy, than those treated with zidovudine/lamivudine/indinavir.