SANGUINATE™ (PEGylated Carboxyhemoglobin Bovine) Improves Cerebral Blood Flow to Vulnerable Brain Regions at Risk of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Background

Delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been linked to focal reductions in cerebral blood flow (CBF) and microvascular impairments in oxygen delivery. Effective therapies that restore flow and oxygen transport to vulnerable brain regions are currently lacking. SANGUINATE is a dual-action carbon monoxide-releasing and hemoglobin-based oxygen transfer agent with efficacy in animal models of focal brain ischemia and tolerability in patients with sickle cell disease.

Methods

We performed a safety and proof-of-principle study in 12 SAH patients at risk of DCI across three escalating doses (160, 240, and 320 mg/kg). We used ¹⁵O-PET (performed at baseline, after SANGUINATE and at 24 h) to evaluate efficacy for improving CBF and restoring flow–metabolism balance (assessed by oxygen extraction fraction [OEF]) to vulnerable regions (defined as baseline OEF ≥ 0.50).

Results

SANGUINATE resulted in a transient rise in mean arterial pressure (116 ± 15–127 ± 13 mm Hg, p = 0.001) that normalized by 24 h and allowed three patients with DCI to be weaned off vasopressors. No adverse events were noted during infusion. Global CBF did not rise (43 ± 8–46 ± 9 ml/100 g/min) although a trend was seen at the highest dose (45 ± 7–51 ± 9, p = 0.044). However, a significant 16% rise in regional CBF associated with reduction in OEF was seen in vulnerable regions, but did not persist at 24 h.

Conclusions

We demonstrated that this novel agent can improve regional CBF and may improve oxygen supply–demand balance. Clinical studies (likely with repeat dosing) are required to evaluate whether this effect can prevent DCI or cerebral infarction.

     

Cutaneous markers of coronary artery disease

Coronary artery disease (CAD) is rapidly increasing in prevalence across the world and particularly in south Asians at a relatively younger age. As atherosclerosis starts in early childhood, the process of risk evaluation must start quite early. The present review addresses the issue of cutaneous markers associated with atherosclerosis, and the strengths and weaknesses of the markers in identifying early coronary atherosclerosis. A diligent search for such clinical markers, namely xanthelasma, xanthoma, arcus juvenilis, acanthosis nigricans, skin tags, ear lobe crease, nicotine stains, premature graying in smokers, hyperpigmented hands in betel quid sellers, central obesity, and signs of peripheral vascular disease may prove to be a rewarding exercise in identifying asymptomatic CAD in high risk individuals.     

Extranodal Rosai-Dorfman disease presenting as an isolated epibulbar mass

Rosai-Dorfman disease is a rare idiopathic disorder characterized by painless lymphadenopathy with cervical involvement in more than 80% cases. We report a case of Rosai-Dorfman disease presenting as an isolated epibulbar mass in a healthy young adult male. Epibulbar involvement in Rosai-Dorfman disease is a rare presentation as can be seen from a review of all literature. The presentation, differential diagnosis and treatment are discussed.     

Success rate and cause of failure for late probing for congenital nasolacrimal duct obstruction

PURPOSE: To evaluate the outcome of late probing for congenital nasolacrimal duct obstruction in children 2 to 6 years old and to identify the cause of failure in these children. METHODS: Records of 65 nasolacrimal duct obstructions in 62 children (39 boys and 23 girls) aged 2 to 6 years who underwent primary probing for congenital nasolacrimal duct obstructions were evaluated. The main observations were the type of obstruction encountered during probing (complex/simple), age at the time of probing, and success rate depending on the type of obstruction. Success was the main outcome measure and was defined as complete resolution of all signs and symptoms at 1 week of follow-up. The Mann-Whitney test for statistical significance was used to compare the results between simple and complex nasolacrimal duct obstructions. RESULTS: Six children had bilateral obstruction. The average age at the time of probing was 37.71 months in children with complex obstruction and 37.27 months in children with simple obstruction. Twenty-one eyes (32.20%) had complex obstruction and 44 eyes (67.69%) had simple obstruction. The success rate was 33% in children with complex obstruction and 97.72% in children with simple obstruction, which was statically significant. The overall success rate of the whole cohort was 76.92%. CONCLUSION: Older children with simple obstruction undergoing late probing had an excellent success rate in this study (97.72%). Complex obstruction is the main risk factor for failure of probing in older children. Probing is a successful and viable option in older children.     

Fournier's gangrene and scrotal ulcerations during all-trans-retinoic acid therapy for acute promyelocytic leukemia

Scrotal ulcers are a rare manifestation in patients with acute promyelocytic leukemia. Fournier's gangrene (FG) is even rarer. We describe three adolescents and young adults who developed scrotal ulcerations during induction with all-trans-retinoic acid. One patient developed FG. These lesions are predominantly seen in Asian population. A good outcome with supportive management occurred in all the cases.     

Dosimetric effects of weight loss or gain during volumetric modulated arc therapy and intensity-modulated radiation therapy for prostate cancer

Weight loss or gain during the course of radiation therapy for prostate cancer can alter the planned dose to the target volumes and critical organs. Typically, source-to-surface distance (SSD) measurements are documented by therapists on a weekly basis to ensure that patients' exterior surface and isocenter-to-skin surface distances remain stable. The radiation oncology team then determines whether the patient has undergone a physical change sufficient to require a new treatment plan. The effect of weight change (SSD increase or decrease) on intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) dosimetry is not well known, and it is unclear when rescanning or replanning is needed. The purpose of this study was to determine the effects of weight change (SSD increase or decrease) on IMRT or VMAT dose delivery in patients with prostate cancer and to determine the SSD change threshold for replanning. Whether IMRT or VMAT provides better dose stability under weight change conditions was also determined. We generated clinical IMRT and VMAT prostate and seminal vesicle treatment plans for varying SSDs for 10 randomly selected patients with prostate cancer. The differences due to SSD change were quantified by a specific dose change for a specified volume of interest. The target mean dose, decreased or increased by 2.9% per 1-cm SSD decrease or increase in IMRT and by 3.6% in VMAT. If the SSD deviation is more than 1 cm, the radiation oncology team should determine whether to continue treatment without modifications, to adjust monitor units, or to resimulate and replan.