Faculty Bibliography

BACKGROUND:Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity. OBJECTIVE:To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS). METHODS:Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 °C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry. RESULTS:The Combat BRS system was able to achieve target range temperature (42-44 °C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose. CONCLUSIONS:Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 °C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.

Corrigendum to: Jeffrey A. Wilhite*, Khemraj Hardowar, Harriet Fisher, Barbara Porter, Andrew B. Wallach, Lisa Altshuler, Kathleen Hanley, Sondra R. Zabar and Colleen C. Gillespie. Clinical problem solving and social determinants of health: a descriptive study using unannounced standardized patients to directly observe how resident physicians respond to social determinants of health. Diagnosis 2020, Volume 7, Issue 3, pages 313-324. https://urldefense.proofpoint.com/v2/url?u=https-3A__doi.org_10&d=DwIBAg&c=j5oPpO0eBH1iio48DtsedeElZfc04rx3ExJHeIIZuCs&r=CY_mkeBghQnUPnp2mckgsNSbUXISJaiBQUhM-Uz9W58&m=TyoCBAKzCpBZ4-uIICybN67eGKr9ePdBC-WexDhSuSM&s=-H9hUl6CWWk07_DiPQFbSmQyI2qWxw4tQLZIEBIpIVY&e= . 1515/dx-2020-0002. Unfortunately, a typographic error in the results portion of the abstract was missed during final stages of proofing and editing. The count of full elicitors should read as 38/68 rather than 28/68, and the % of negative elicitors is 23%. The corrected results read as follows: Residents fell into three groups when it came to clinical problem-solving around a housing trigger for asthma: those who failed to ask about housing and therefore did not uncover mold as a potential trigger (neglectors - 21%; 14/68); those who asked about housing in negative ways that prevented disclosure and response (negative elicitors - 23%, 16/68); and those who elicited and explored the mold issue (full elicitors - 56%; 38/68).
Copyright