Effects of cobalt and chromium ions on glycolytic flux and the stabilization of hypoxia‐inducible factor‐1α in macrophages in vitro

Implant wear and corrosion have been associated with adverse tissue reactions that can lead to implant failure. Wear and corrosion products are therefore of great clinical concern. For example, Co²⁺ and Cr³⁺ originating from CoCrMo‐based implants have been shown to induce a proinflammatory response in macrophages in vitro. Previous studies have also shown that the polarization of macrophages by some proinflammatory stimuli is associated with a hypoxia‐inducible factor‐1α (HIF‐1α)‐dependent metabolic shift from oxidative phosphorylation (OXPHOS) towards glycolysis. However, the potential of Co²⁺ and Cr³⁺ to induce this metabolic shift, which plays a determining role in the proinflammatory response of macrophages, remains largely unexplored. We recently demonstrated that Co²⁺, but not Cr³⁺, increased oxidative stress and decreased OXPHOS in RAW 264.7 murine macrophages. In the present study, we analyzed the effects of Co²⁺ and Cr³⁺ on glycolytic flux and HIF‐1α stabilization in the same experimental model. Cells were exposed to 6 to 24 ppm Co²⁺ or 50 to 250 ppm Cr³⁺. Glycolytic flux was determined by analyzing extracellular flux and lactate production, while HIF‐1α stabilization was analyzed by immunoblotting. Results showed that Co²⁺, and to a lesser extent Cr³⁺, increased glycolytic flux; however, only Co²⁺ acted through HIF‐1α stabilization. Overall, these results, together with our previous results showing that Co²⁺ increases oxidative stress and decreases OXPHOS, suggest that Co²⁺ (but not Cr³⁺) can induce a HIF‐1α‐dependent metabolic shift from OXPHOS towards glycolysis in macrophages. This metabolic shift may play an early and pivotal role in the inflammatory response induced by Co²⁺ in the periprosthetic environment.     

Establishment of a formal program for retinoblastoma: Feasibility of clinical coordination across borders and impact on outcome

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age‐adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.     

Prevalence of phonatory symptoms in patients with type 2 diabetes mellitus

To look at the prevalence of phonatory symptoms in patients with type 2 diabetes mellitus. The correlation between these symptoms with duration of the disease, glycemic control, and neuropathy will be described. A total of 105 consecutive patients diagnosed with type 2 diabetes mellitus by their primary endocrinologist were evaluated. A control group consisting of 33 healthy subjects was recruited for this study. Demographic data included: age, gender, allergy, smoking, duration of the disease, glycemic control, and presence or absence of neuropathy. Subjects were also asked about the presence or absence of the following symptoms: hoarseness, vocal tiring or fatigue, vocal straining, and aphonia or complete loss of voice. Patients were also asked to fill out the Voice Handicap Index 10. The mean age of patients with diabetes was 53.21 + 9.68 years with male-to-female ratio of 2/3. The most common phonatory symptoms were vocal tiring or fatigue and hoarseness (34.3 and 33.3 %). There was a significant difference in the prevalence of hoarseness and vocal straining (p value 0.045 and 0.015, respectively) compared to controls. There was a significant correlation between glycemic control, neuropathy, and hoarseness (p value 0.030 and 0.001, respectively). Vocal straining and aphonia also correlated significantly with the presence of neuropathy. Close to 16 % of diabetic patients had a VHI-10 above or equal to 7. Diabetic patients are more likely to have phonatory symptoms compared to controls, namely straining and hoarseness. One out of seven patients with diabetes has reported that phonatory symptoms had a significant impact on their quality of life. The presence of neuropathy and poor glycemic control should alert the treating physician to these vocal complaints.     

A randomized single-blind trial of whole versus split-dose polyethylene glycol-electrolyte solution for colonoscopy preparation

BACKGROUND: Colonoscopy preparation regimens are often poorly tolerated because they require use of large-volume bowel preparation solution and diet restrictions for adequate cleansing. This study evaluated the efficacy and tolerability of a split-dose polyethylene glycol-electrolyte solution plus bisacodyl and a regular diet. METHODS: A total of 187 patients (104 men, 83 women; age range 18-91 years) were randomly assigned to receive either 3 L of polyethylene glycol-electrolyte solution (n = 96; Group A) with a liquid diet on the day before colonoscopy, or 2 L of polyethylene glycol-electrolyte solution, one tablet of bisacodyl, and a minimally restricted diet on the day before colonoscopy, and then 1 L of the same solution on the day of colonoscopy (n = 91; Group B). Acceptability, adverse events, and willingness to retake the preparation were assessed by questionnaire. The quality of the preparation was graded by an endoscopist, blinded to the type of preparation, by using a previously described scale (excellent to poor). RESULTS: There were 96 patients in Group A and 91 in Group B. Colon cleansing was significantly better in Group B with regard to the overall quality of the preparation (p lt; 0.05). Compliance was significantly higher in Group B as evidenced by the lower number of patients who discontinued the preparation (4 vs. 15; p = 0.02) because of side effects such as nausea or vomiting. The degree of discomfort, adverse events, and willingness to retake the preparation were not significantly different between the groups. CONCLUSIONS: Colonic preparation with split-dose polyethylene glycol-electrolyte provided better quality colon cleansing and higher compliance, with less dietary restrictions, than preparation with whole-dose polyethylene glycol-electrolyte.