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.     

Risk factors for the development of acute lung injury in patients with infectious pneumonia

ABSTRACT: INTRODUCTION: Although pneumonia has been identified as the single most common risk factor for acute lung injury (ALI), we have a limited knowledge as to why ALI develops in some patients with pneumonia and not in others. The objective of this study was to determine frequency, risk factors, and outcome of ALI in patients with infectious pneumonia. METHODS: A retrospective cohort study of adult patients with microbiologically positive pneumonia, hospitalized at two Mayo Clinic Rochester hospitals between January 1, 2005, and December 31, 2007. In a subsequent nested case-control analysis, we evaluated the differences in prehospital and intrahospital exposures between patients with and without ALI/acute respiratory distress syndrome (ARDS) matched by specific pathogen, isolation site, gender, and closest age in a 1:1 manner. RESULTS: The study included 596 patients; 365 (61.2%) were men. The median age was 65 (IQR, 53 to 75) years. In total, 171 patients (28.7%) were diagnosed with ALI. The occurrence of ALI was less frequent in bacterial (n = 99 of 412, 24%) compared with viral (n = 19 of 55, 35%), fungal (n = 39 of 95, 41%), and mixed isolates pneumonias (n = 14 of 34, 41%; P = 0.002). After adjusting for baseline severity of illness and comorbidities, patients in whom ALI developed had a markedly increased risk of hospital death (ORadj 9.7; 95% CI, 6.0 to 15.9). In a nested case-control study, presence of shock (OR, 8.9; 95% CI, 2.8 to 45.9), inappropriate initial antimicrobial treatment (OR, 3.2; 95% CI, 1.3 to 8.5), and transfusions (OR, 4.8; 95% CI, 1.5 to 19.6) independently predicted ALI development. CONCLUSIONS: The development of ALI among patients hospitalized with infectious pneumonia varied among pulmonary pathogens and was associated with increased mortality. Inappropriate initial antimicrobial treatment and transfusion predict the development of ALI independent of pathogen.     

Low versus standard dose intravenous alteplase in the treatment of acute ischemic stroke in Egyptian patients

Objectives:To assess low dose altepase outcome and safety in comparison with a standard-dose regimen for acute ischemic stroke treatment in Egyptian patients.Materials:An observational prospective cohort non-randomized single blinded study was carried out during the period from November 2017 to December 2018. Eighty Egyptian acute ischemic stroke patients, all eligible for intravenous alteplase, were subdivided into 2 groups (40 patients in each group). Patients were thrombolysed at a dose of 0.6 mg/kg in the first group and 0.9 mg/kg in the second group. Both groups were compared in regard to safety and outcome. Safety was expressed by the rate of symptomatic intracranial hemorrhage (SICH) and 3 months mortality, while outcome was expressed by favorable outcomes at three months (modified Rankin Scale [mRS] of 0 to 2).Results:In the first group, 69.2% (n=27) achieved favorable outcomes at 90 days compared with 64.1% (n=25) in the second group (p=0.631). Ninety-day mortality was 5% (n=2) in the first group versus 2.5% (n=1) in the second group (p=0.556). Symptomatic intracranial hemorrhage was noted in 3 patients in the second group and zero patients in the first group (p=0.077).Conclusion:Low-dose alteplase could be a practical alternative for Egyptian populations with acute ischemic stroke especially in 3 to 4.5 hours window.

Cerebrovascular stroke is the second death and the seventh disability leading cause worldwide.¹ Tissue-type plasminogen activator (tPA) alteplase was the first medication approved by the Food and Drug Administration (FDA) for the acute ischemic stroke (AIS) treatment on June 1996, within 3 hours of stroke onset with a recommended dose of 0.9 mg/kg (maximum 90mg).² In 2008, the safety of using alteplase within 3 to 4.5 hours of stroke onset was approved by the Safe Implementation of Treatments in Stroke International Stroke Thrombolysis Registry (SITS -ISTR)³ and the European Cooperative Acute Stroke Study (ECASS III).⁴ However, thrombolytic therapy use has not been widely adopted, especially in developing countries. The restricted time window (3 to 4.5 hours), intracerebral hemorrhage (ICH) risk and the drug high cost are major obstacles preventing its broad application.⁵ Coagulation and fibrinolysis responses differ among different races, which increase symptomatic intracerebral hemorrhage (SICH) risk with standard-dose alteplase⁶ in Asian populations, many Asian neurologists considered alteplase low dose to be a better alternative for ischemic stroke treatment. Many studies had been conducted in order to prove the efficacy and safety of Alteplase low dose.^7-9 One of these studies was the Japan Alteplase Clinical Trial (J-ACT) conducted by Yamaguchi et al¹⁰ According to this study, using a 0.6 mg/kg dose of intravenous recombinant tissue plasminogen activator (rtPA) in Japanese patients was safe and effective. Despite the relatively stroke high rate among Egyptian populations, 963/100,000 inhabitants, only less than 1% of stroke patients receive intravenous thrombolysis. A major reason for this is the drug cost.^11,12 Low-dose regimens (0.6 mg/kg) use will lower the economic burden of thrombolytic therapy in the community and will greatly promote the implementation of this therapy in Egypt. Our study aim was to assess the outcome and safety of alteplase low dose in comparison to the standard-dose regimen in AIS treatment in Egypt.     

Dose-dependent effect of histamine on liver function markers in immunized rabbits

ObjectiveThe present study was designed to delineate the hepatotoxicological roles of histamine dose-dependently in immunized rabbits.MethodsThe cohort comprised of three groups (II, III and IV), containing 18 rabbits each, and received subcutaneous histamine 50 μg/kg, 100 μg/kg and 200 μg/kg, respectively for 10 days (b.i.d., starting from 3 days prior to immunization until 7 days after immunization). Group I (control, n = 18) received subcutaneous sterile distilled water for 10 days. They were subsequently immunized at day 3 with intravenous injection of SRBC (1 × 10⁹ cells/ml). Blood samples were collected on pre-immunization (pre-I) day 0, as well as on days 7-, 14-, 21-, 28- and 58-post-immunization (post-I). Biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin [total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB)] were determined.ResultsGroups II and IV revealed a significant decrease (on day 0-pre-I) and a significant increase (on days 7-, 14-, 21-, 28- and 58-post-I) in ALT and AST levels, when compared with the corresponding values of groups I and III while group II showed a significant increase in ALT and AST levels as compared to group IV. ALP levels in groups II, III and IV showed a significant enhancement when compared with group I. Moreover, results of TB, DB and IB demonstrated increased levels in group III when compared with groups I, II and IV. The results were found statistically significant (p < 0.05).ConclusionShort-term treatment of histamine produces dose-dependent differential patterns of hepatic dysfunctions suggestive mild liver degeneration warranting further long-term studies.     

Multivisceral organ failure related to leptospirosis in pregnant patient

Leptospirosis is the most widespread zoonosis in the world. It is caused by pathogenic leptospira infection. This infection is also an uncommon cause of hepatorenal failure. Indeed, hemolysis, elevated liver enzyme levels and low platelet count syndrome, and acute fatty liver of pregnancy are specific to the pregnant state. Leptospirosis is rarely described in pregnancy; it might mimic puerperal sepsis or hepatorenal failure associated with pregnancy induced hypertension. We report a case of leptospirosis presenting as multiple organ failure during third trimester of pregnancy with a good outcome.