COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms.

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. SARS-CoV-2 infection is necessary but not sufficient for development of clinical COVID-19 disease. Currently, there are no approved pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We have investigated several plausible hypotheses for famotidine activity including antiviral and host-mediated mechanisms of action. We propose that the principal mechanism of action of famotidine for relieving COVID-19 symptoms involves on-target histamine receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release. Based on these findings and associated hypothesis, new COVID-19 multi-drug treatment strategies based on repurposing well-characterized drugs are being developed and clinically tested, and many of these drugs are available worldwide in inexpensive generic oral forms suitable for both outpatient and inpatient treatment of COVID-19 disease.

Hounsfield unit density accurately predicts ESWL success.

Extracorporeal shockwave lithotripsy (ESWL) is a commonly used non-invasive treatment for urolithiasis. Helical CT scans provide much better and detailed imaging of the patient with urolithiasis including the ability to measure density of urinary stones. In this study we tested the hypothesis that density of urinary calculi as measured by CT can predict successful ESWL treatment. 198 patients were treated at Alaska Urological Associates with ESWL between January 2002 and April 2004. Of these 101 met study inclusion with accessible CT scans and stones ranging from 5-15 mm. Follow-up imaging demonstrated stone freedom in 74.2%. The overall mean Houndsfield density value for stone-free compared to residual stone groups were significantly different ( 93.61 vs 122.80 p < 0.0001). We determined by receiver operator curve (ROC) that HDV of 93 or less carries a 90% or better chance of stone freedom following ESWL for upper tract calculi between 5-15mm.

NMP22 BladderChek Test: point-of-care technology with life- and money-saving potential.

A new, relatively obscure tumor marker assay, the NMP22 BladderChek Test (Matritech, Inc.), represents a paradigm shift in the diagnosis and management of urinary bladder cancer (transitional cell carcinoma). Specifically, BladderChek should be employed every time a cystoscopy is performed, with corresponding changes in the diagnostic protocol and the guidelines of the American Urological Association for the diagnosis and management of bladder cancer. Currently, cystoscopy is the reference standard and NMP22 BladderChek Test in combination with cystoscopy improves the performance of cystoscopy. At every stage of disease, BladderChek provides a higher sensitivity for the detection of bladder cancer than cytology, which now represents the adjunctive standard of care. Moreover, BladderChek is four-times more sensitive than cytology and is available at half the cost. Early detection of bladder cancer improves prognosis, quality of life and survival. BladderChek may be analogous to the prostate-specific antigen test and eventually expand beyond the urologic setting into the primary care setting for the testing of high-risk patients characterized by smoking history, occupational exposures or age.

Ertapenem versus ceftriaxone followed by appropriate oral therapy for treatment of complicated urinary tract infections in adults: results of a prospective, randomized, double-blind multicenter study.

The efficacy and safety of intravenous (i.v.) ertapenem (1 g once a day) with the option to switch to an oral agent for treatment of adults with complicated urinary tract infections (UTIs) were compared with that of i.v. ceftriaxone (1 g daily) with the same oral switch option in a multicenter, double-blind, prospective, randomized study. At entry, 592 patients were assigned to one of two strata: acute pyelonephritis or other complicated UTI without acute pyelonephritis. After a minimum of 3 days, patients could be switched to an oral antimicrobial agent. A total of 159 patients in the ertapenem group and 171 patients in the ceftriaxone group were microbiologically evaluable. Approximately 95% of patients in each treatment group were switched to oral therapy. The most common pathogens were Escherichia coli and Klebsiella pneumoniae. At the primary efficacy endpoint 5 to 9 days after treatment, 91.8% of patients who received ertapenem and 93.0% of those who received ceftriaxone had a favorable microbiological response (95% confidence interval for the difference, adjusting for strata, -7.6 to 5.1%), indicating that outcomes in the two treatment groups were equivalent. Microbiological success rates for the two treatment groups were similar when compared by stratum and also by severity of infection. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. In this study, ertapenem was as effective as ceftriaxone for the initial treatment of complicated UTIs in adults, was generally well tolerated, and had a similar overall safety profile.