Association of the CCR5Δ32 Mutant Genotype with Sickle Cell Disease in Egyptian Patients

Abstract

Sickle cell disease is considered the most common single base mutation in the world, with >250,000 new patients being discovered each year. It consists of a wide spectrum of clinical presentations and complications. The CCR5Δ32 is the mutant genotype of C–C chemokine receptor 5 (CCR5). It is widely distributed due to several micro organisms that target macrophages in different populations. Theoretically, CCR5Δ32 confers an advantage to sickle cell disease patients. The chronic inflammatory response is the main pathogenesis in sickle cell disease, thus, the presence of the null CCR5Δ32 mutant genotype prevents the Th1-type immune response caused by the CCR5 chemokine receptor. This study aimed to define the true incidence of the CCR5Δ32 mutant genotype and to correlate its presence with the clinical and/or the radiological findings in sickle cell disease patients. We proposed decreased morbidity and prolonged survival of sickle cell disease patients carrying the CCR5Δ32 genotype. The study showed relatively the same prevalence (5.1%) of the CCR5Δ32 mutant genotype found in 500 sickle cell disease patients when compared to 1000 healthy controls (5.0%) with the same ethnic background. Despite the near prevalence of the incidence to controls, we suggest that CCR5Δ32 is relatively beneficial to sickle cell disease patients as polymorphic patients showed uncomplicated clinical presentation in contrast to other patients without the CCR5Δ32.     

Is Colonoscopic Screening Necessary for Patients with Gastric Adenoma or Cancer?

Background

Since colorectal adenoma or cancer is commonly associated with gastric adenoma or cancer, early colorectal adenoma detection can affect the survival of gastric adenoma or cancer patients.

Aims

The purpose here was to investigate the colorectal adenoma or cancer prevalence and evaluate the necessity for screening colonoscopy in gastric adenoma or cancer patients.

Patients and methods

From September 2005 through August 2010, 857 patients younger than 70 years who had gastric adenoma or cancer were enrolled. Healthy age- and sex-matched controls were selected from the general screening population. The prevalence and risk of colorectal adenoma or cancer were compared between the participants and the controls.

Results

Data from 416 patients in the gastric neoplasm group (123 with gastric adenoma and 293 with gastric cancer) and 416 healthy control group participants were included in the statistical analysis. The presence of gastric adenoma or cancer was an independent risk factor for colorectal neoplasm (OR = 1.348, 95 % CI = 1.001–1.815). Patients with diffuse type gastric cancer had a lower prevalence of colorectal adenoma or cancer than those with gastric adenoma or intestinal type cancer. In gastric cancer patients younger than 50 years, intestinal type histology was significantly associated with colorectal adenoma or cancer (OR = 3.838, 95 % CI = 1.077–13.677).

Conclusions

The colorectal adenoma or cancer risk was significantly increased in patients with gastric adenoma or cancer. Therefore, screening colonoscopy should be considered for gastric adenoma or cancer patients including young patients, in the case of intestinal type gastric cancer.     

Is Maximum Conservative Management an Equivalent Treatment Option to Dialysis for Elderly Patients with Significant Comorbid Disease?

Background and objectives: There is ongoing growth of elderly populations with ESRD in Western Europe and North America. In our center, we offer an alternative care pathway of ‘maximum conservative management’ (MCM) to patients who elect not to start dialysis, often because of a heavy burden of comorbid illness and advanced age. The objective of our study was to compare clinical outcomes for patients who had ESRD and chose either MCM or renal replacement therapy (RRT).Design, setting, participants, & measurements: This is an observational study of a single-center cohort in the United Kingdom that evaluating 202 elderly (≥70 yr) patients who had ESRD and had chosen either MCM (n = 29) or RRT (n = 173). We report survival, hospitalization rates, and location of death for this cohort. Survival was measured from a standardized ‘threshold’ estimated GFR of 10.8 ml/min per 1.73 m².Results: Median survival, including the first 90 d, was 37.8 mo (range 0 to 106 mo) for RRT patients and 13.9 mo (range 2 to 44) for MCM patients (P < 0.01). RRT patients had higher rates of hospitalization (0.069 [95% confidence interval (CI) 0.068 to 0.070]) versus 0.043 [95% CI 0.040 to 0.047] hospital days/patient-days survived) compared with MCM patients. MCM patients were significantly more likely to die at home or in a hospice (odds ratio 4.15; 95% CI 1.67 to 10.25). A survey of the literature describing elderly ESRD outcomes is also presented.Conclusions: Dialysis prolongs survival for elderly patients who have ESRD with significant comorbidity by approximately 2 yr; however, patients who choose MCM can survive a substantial length of time, achieving similar numbers of hospital-free days to patients who choose hemodialysis.Although the overall incidence of ESRD in Western Europe and North America seems to have leveled off in recent years, this trend has not been seen for people who are older than 65 yr. Among the elderly, there is ongoing growth of incident and prevalent ESRD populations as well as a steady increase in rates of acceptance of the elderly onto dialysis programs (1–3). Increased longevity, coupled with technical advances and heightened public expectation, has contributed to an unprecedented increase in demand for dialysis therapies in older age groups (2). The burden of comorbid disease is higher in this group of patients (4) and has been clearly shown to affect survival (5). For a select group of elderly patients with a heavy burden of comorbid illness, although dialysis may be technically feasible, the short-term mortality is often very high, particularly in those with advanced cardiovascular disease and/or diabetes (6). Transportation to and from hemodialysis units is often an all-day affair for patients with limited mobility, leaving very little time for other activities on hemodialysis days. Emotional investment of both patients and health care staff in the life-prolonging nature of renal replacement therapy (RRT) may result in unnecessary medicalization of death, manifest by invasive tests, procedures and hospitalizations whose benefits are marginal at best (7). Previous authors have suggested that dialysis patients are more likely to die in hospital rather than at home or in hospice (8,9).A growing number of nephrology programs in the United Kingdom are offering ongoing follow-up and multidisciplinary support to patients who have ESRD and choose not to start dialysis. It has been variously described as ‘conservative management,’ ‘maximum conservative management’ (MCM), nondialysis treatment, and ‘palliative renal care’; however, little information on patient outcomes is available. There has been increasing interest in recent years in quantifying the survival benefit offered by dialysis therapies to elderly patients with ESRD and a heavy burden of comorbid disease (10,11). The objective of our study was to compare clinical outcomes for a single-center cohort of 202 elderly (≥70 yr) patients who had ESRD and chose either MCM or RRT. We describe survival, hospitalization rates, and location of death for this cohort.     

Adult epiglottitis. Is there a role for the fiberoptic bronchoscope?

The "cherry red" laryngoscopic appearance of adult epiglottitis, as visualized through a fiberscope, is reproduced. The possible role of the fiberoptic bronchoscope, both as a diagnostic aid and as a means of facilitating endotracheal intubation, in this condition, is discussed.     

How Is the Liver Primed or Sensitized for Alcoholic Liver Disease?

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hidekazu Tsukamoto and Yoshiyuki Takei. The presentations were (1) Tribute to Professor Rajendar K. Chawla, by Craig J. McClain; (2) Dysregulated TNF signaling in alcoholic liver disease, by Craig J. McClain, S. Joshi-Barve, D. Hill, J Schmidt, I. Deaciuc, and S. Barve; (3) The role of mitochondria in ethanol-mediated sensitization of the liver, by Anna Colell, Carmen Garcia-Ruiz, Neil Kaplowitz, and Jose C. Fernandez-Checa; (4) A peroxisome proliferator (bezafibrate) can prevent superoxide anion release into hepatic sinusoid after acute ethanol administration, by Hirokazu Yokoyama, Yukishige Okamura, Yuji Nakamura, and Hiromasa Ishii; (5) S-adenosylmethionine affects tumor necrosis factor-α gene expression in macrophages, by Rajendar K. Chawla, S. Barve, S. Joshi-Barve, W. Watson, W. Nelson, and C. McClain; (6) Iron, retinoic acid and hepatic macrophage TNFα gene expression in ALD, by Hidekazu Tsukamoto, Min Lin, Mitsuru Ohata, and Kenta Motomura; and (7) Role of Kupffer cells and gut-derived endotoxin in alcoholic liver injury, by N. Enomoto, K. Ikejima, T. Kitamura, H. Oide, Y. Takei, M. Hirose, B. U. Bradford, C. A. Rivera, H. Kono, S. Peter, S. Yamashina, A. Konno, M. Ishikawa, H. Shimizu, N. Sato, and R. Thurman.     

Coinheritance of α-Thalassemia Decreases the Risk of Cerebrovascular Disease in a Cohort of Children with Sickle Cell Anemia

The study estimated α-thalassemia (α-thal) prevalence and assessed its associations with clinical and hematological features in a random sample of Brazilian children with sickle cell anemia (208 Hb SS and 13 Hb S-β⁰-thal). α-Thalassemia genotyping was carried out by multiplex polymerase chain reaction (m-PCR) for seven alleles. Clinical and hematological data were retrieved from the 221 children's medical files. Their ages ranged from 2.5 to 10.4 years. Of the Hb SS children, 27.9% carried –α^3.7/αα and 1.4% –α^3.7/–α^3.7. The presence of α-thal was significantly associated with reduction in MCV, MCH, WBC values and reticulocyte counts. No significant association with blood transfusion or acute chest syndrome (ACS), was found. α-Thalassemia genotypes were strongly associated with reduction in risk for cerebrovascular disease (CVD) (conditional and abnormal transcranial Doppler or stroke; p = 0.007). The interaction of α-thal with other modulating factors should be investigated in order to define subphenotypes of the disease and to use them as clinical tools in the follow-up care of patients.     

What is the Ideal Blood Pressure Goal for Patients with Stage III or Higher Chronic Kidney Disease?

Hypertension and chronic kidney disease (CKD) are public health problems well known to the national and international medical communities. Blood pressure (BP) control in patients with CKD stage III and IV plays a key factor in reducing cardiovascular risk and renal disease progression. We conducted a literature review of recent studies addressing BP targets and cardiorenal outcomes in patients with CKD. Multiple studies demonstrated cardiovascular benefits associated with greater BP reduction. Nevertheless, a U-shaped relationship between BP, cardiovascular events, and renal function was present. In patients with CKD stage III and IV, a BP less than 140/90 mm Hg appeared to be a reasonable target. Moreover, in patients with CKD and proteinuria of more than 1 g/day, a target systolic BP of 120 to 130 mm Hg and diastolic BP of 70 to 80 mm Hg yielded the greatest benefit while avoiding most of the adverse cardiovascular outcomes associated with lower levels of BP.     

Preliminary Evaluation of a Point-of-Care Testing Device (SickleSCAN™) in Screening for Sickle Cell Disease

Sickle cell disease affects about 150,000 births annually in Nigeria. Early diagnosis is hampered by factors such as centralized and urban localization of laboratories, high cost of diagnostic equipment and inadequate skilled manpower to operate them. The need for a low-cost, portable, easy-to-use diagnostic test for sickle cell disease is critical, especially in resource-poor countries. In this study, we evaluated the performance characteristics of a novel point-of-care testing device (SickleSCAN?), and its acceptability and feasibility, as a possible screening tool for sickle cell disease. In the first phase, we assessed the performance characteristics of SickleSCAN? by evaluating 57 subjects comprising both children and adults attending a primary health center, for Hb SS (β^S/β^S; HBB: c.20A>T), Hb SC (β^S/β^C; HBB: c.19G>A) and Hb AS (β^A/β^S) using SickleSCAN?, cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC). Performance characteristics such as diagnostic sensitivity and specificity were compared to HPLC as a standard method. We subsequently undertook a second phase wherein the acceptability and feasibility of the device for sickle cell disease screening, was evaluated using semi-structured and structured questionnaires among 197 healthcare personnel and 221 subjects, respectively. Sickle cell disease was carried by 3.4% of the subjects. The diagnostic sensitivity, specificity and test efficiency of SickleSCAN? for sickle cell disease (Hb SS and Hb SC), were 100.0, 98.2 and 98.2%, respectively. Findings from this study showed SickleSCAN? to be a viable screening tool that can easily be applied in community-based screening for early diagnosis of sickle cell disease with little expertise and low cost.     

Anaphylaxis and Mast Cell Disease: What Is the Risk?

Mastocytosis is a proliferative disorder of the hematopoietic mast cell progenitor that results from expansion of a clone carrying the D816V c-kit mutation. Based on the dramatic increase in incidence of anaphylaxis in patients with mastocytosis, recent studies analyzed the presence of clonal mast cell markers, including D816V c-kit mutation, in patients with recurrent IgE- and non-IgE-mediated anaphylaxis. These studies demonstrated the presence of an aberrant mast cell clone in a significant proportion of patients with unexplained anaphylaxis, or anaphylaxis due to hymenoptera venom. Clonal mast cell disease should be suspected in particular in patients presenting with profound cardiovascular manifestations such as hypotension and syncope in the absence of urticaria.     

Do Automated Red Cell Exchanges Relieve Priapism In Patients with Sickle Cell Anemia?

Abstract: Priapism is a dramatic, painful complication for some men afflicted by sickle cell anemia. Although the natural history remains unclear, many believe replacing the patient's abnormal red blood cells (RBCs) with normal RBCs by apheresis is effective. However, no controlled trials have demonstrated its effectiveness. We exchanged 7 men after medical management failed. All procedures reduced sickle hemoglobin levels to < 30%. Two patients underwent emergency automated red cell exchanges without any detumescence or reduction of pain. The remaining 5 patients were exchanged non‐emergently; 4 experienced no detumescence or relief of pain. One adult experienced resolution 8 h postexchange. However, he had a history of “stuttering” priapism. All required decompression procedures. Automated RBC exchanges were not effective in achieving detumescence or reducing pain.