Hepatitis B vaccine related‐myelitis?*

We present four incidental cases that developed partial myelitis following the administration of hepatitis B vaccine in 1998. The first two cases, a 33-year-old man and a 42-year-old woman developed progressive sensory symptoms without motor involvement within 4 weeks following the vaccination. Their magnetic resonance imaging (MRI) disclosed similar lesions consistent with myelitis at their cervical spinal cord. A comparable inflammatory lesion was seen at the T9-T10 levels of the spinal cord in the third case, who was a 40-year-old woman presenting with numbness in her legs and urinary retention following the vaccination. The fourth case who was a 42-year-old woman, presented with sensory symptoms in her left extremities, which developed 3 months after the vaccination. Her MRI showed a hyperintense lesion at C6. She also had two tiny lesions in her cranial MRI. In all cases, there was no history of preceding infections and no clinical evidence suggestive of any other disorders that may cause myelopathy. All patients recovered completely within 3 months with the exception of the third patient who developed new neurological symptoms after 12 months. Similar clinical and imaging presentation of myelitis following hepatitis B vaccination within a 1 year period with no other demonstrable clinical and laboratory evidence for any other disorder raise the probability of a causal link between these two events.     

Everolimus for renal cell carcinoma: predictive factors for response and future directions

Mammalian target of rapamycin (mTOR) inhibitors have emerged as a major addition to the therapeutic armamentarium for renal cell carcinoma. Temsirolimus extended survival when employed as frontline therapy for poor-risk advanced renal cell carcinoma. Everolimus has demonstrated improved progression-free survival for all risk groups of RCC in the salvage setting following other anti-angiogenic agents. Preliminary data indicates that baseline activation of the mTOR signaling pathway and increased FDG-PET uptake as well as early pharmacodynamic modulations of the mTOR pathway and down-modulation of FDG-PET uptake may predict for the activity of mTOR inhibitors. Ongoing trials are attempting to validate these data with everolimus therapy for metastatic RCC and may enable the goal of personalized therapy.     

Suppression of the hepatic microsomal cytochrome P-450 dependent mixed function oxidase activities in golden hamster during Leishmania donovani infection

Experimental infection of golden hamsters with Leishmania donovani caused significant alterations in the hepatic microsomal mixed function oxidase system. Gross examination of liver indicated hepatomegaly. Microsomal protein contents were only marginally elevated. Cytochrome P-450 as well as haem contents were significantly decreased and it directly correlated with the degree of infection. Cytochrome b5 exhibited elevation at lower degrees of infection which came down to control levels at the peak infection. Concomitant suppression was also noticed in cytochrome P-450 dependent monooxygenase activities, viz. aniline hydroxylase, benzo[a]pyrene hydroxylase and aminopyrine N-demethylase. No significant change was observed in NADH-cytochrome b5 reductase and NADPH-cytochrome c reductase. The results indicate suppression of hepatic microsomal MFO activities during visceral leishmaniasis.     

Asthma Control and Patient Satisfaction Among Early Pediatric Users of Montelukast

Objective: To assess asthma control and patient satisfaction among pediatric users of montelukast in a clinical practice setting.

Study Design: A prospective study of 175 children with persistent asthma, 6 to 14 years of age, who initiated treatment with montelukast between Feb-1998 and Aug-1998, in primary care and pediatric offices across the United States. Data on asthma control and satisfaction with treatment was collected in physicians' offices after enrollment and by survey to the patients' homes at 1 month of treatment.

Results: Across the study population, improvements in mean scores for asthma control and parent satisfaction were observed at the 1-month follow-up compared with baseline. At 1 month, 57.7% of patients had none of four issues indicative of poor asthma control, compared with 19.4% at baseline. Similarly, after 1 month of treatment with montelukast, 2.7 times as many parents reported being very satisfied with asthma therapy (using montelukast) compared with the previous controller therapy regimen at baseline. During the 1-month follow-up period, montelukast was used as the only controller medication by 18.3% of patients, and in combination with another controller medication by 81.7%.

Conclusions: Observations from this study over one month suggest that a significant percentage of pediatric patients successfully managed their asthma with montelukast and their parents were satisfied with their medication, compared to baseline.     

Flat foot and femoral anteversion in children—A prospective study

BackgroundFlat foot in children during the first years of life evokes significant parental concern. Flat foot, intoeing and femoral anteversion may well be differential dimensions of developmental pathodynamics with potential for inter-related developmental correction. While correlation of femoral anteversion with intoeing is documented, its relationship with flat foot remains unclear.ObjectiveThe aim of this prospective study is to investigate the relationship between flat foot and internal rotation of hip, indirectly femoral anteversion.Methods651 Children, 339 boys and 312 girls, aged 3–6 years, were examined and Contact Index II for flat foot as well as internal rotation of hip measured. 82 children with other foot and leg deformities were excluded from further analysis.ResultsOut of 569 children, 95 (16.7%) had flat feet – 56 bilateral, 39 unilateral – with Contact Index II of 0.88 or above. All children with flat feet (and none of the normal 474) had raised internal rotation of hip (mean 69.9°, range 62–80°).ConclusionRegression analysis established an unequivocal and highly significant statistical relationship between flat foot and increased internal rotation of hip (F = 168.1, p < 0.001, r = 0.53) in children between 3 and 6 years.     

Characterizing trends in treatment modalities for localized muscle-invasive bladder cancer in the pre-immunotherapy era

Introduction

Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which treatment strategies are continuously evolving. We characterized trends in treatment modalities for MIBC from 2004 to 2013 (the “pre-immunotherapy era”) and identified predictors of receiving the current standard of care treatment: neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC).

Methods

We used the National Cancer Database to identify individuals diagnosed with clinically localized MIBC from 2004 to 2013. We calculated the yearly prevalence of NAC followed by RC, RC as first treatment, trimodal therapy, chemotherapy and/or radiation alone, and no treatment. We then identified factors associated with receiving NAC prior to RC.

Results

There was a notable increase in the use of NAC followed by RC over the study period, from 3.68% in 2004 to 14.83% in 2013 (P?<?0.001). Factors associated with decreased odds of receiving this regimen included being older, Black, uninsured, less educated, and more burdened by comorbidities. Rates of trimodal therapy and chemotherapy and/or radiation alone remained relatively constant (approximately 5 and 17%, respectively). There was a consistent decline in the proportion of patients who did not receive any treatment, down to 34.20% in 2013.

Conclusion

Trends in localized MIBC treatment have evolved substantially since the early 2000s, and certain patient characteristics are associated with lower odds of receiving the current standard of care. This serves as a foundation from which to judge the impact of the upcoming immunotherapy era on the treatment landscape for this disease.

     

Phase 2 Trial of Gemcitabine,Cisplatin, plus Ipilimumab in Patients with Metastatic Urothelial Cancer and Impact of DNA Damage Response Gene Mutations on Outcomes

Background

Chemotherapy may exert immunomodulatory effects, thereby combining favorably with the immune checkpoint blockade. The pharmacodynamic effects of such combinations, and potential predictive biomarkers, remain unexplored.