Ureteroscopy with thulium fiber laser lithotripsy results in shorter operating times and large cost savings.

PURPOSE: Prolonged ureteroscopy (URS) is associated with complications including ureteral perforation, stricture, and urosepsis. As laser lithotripsy is one of the most common urologic procedures, small cost savings per case can have a large financial impact. This retrospective study was designed to determine if Thulium fiber laser (TFL) lithotripsy decreases operative time and costs compared to standard Holmium:YAG (Ho:YAG) lithotripsy without pulse modulation. METHODS: A retrospective review of URS with laser lithotripsy was conducted for 152 cases performed from August 2020 to January 2021. Variables including cumulative stone size, location, chemical composition, prior ureteral stenting, and ureteral access sheath use were recorded for each case. A cost benefit analysis was performed to show projected cost savings due to potentially decreased operative times. RESULTS: Compared to Ho:YAG, use of TFL resulted in an average decrease of 12.9 min per case (p = .021, 95% CI [2.03-23.85]). In subgroup analysis of cases with cumulative stone diameter less than 15 mm, the difference was 14.0 min (p = .007, CI [3.95-23.95]). For cases less than 10 mm, the mean difference was 17.3 min in favor of TFL (p = .002, 95% CI [6.89-27.62]). This ~ 13 min reduction in operative time resulted in saving $440/case in direct operating room costs giving our institution a range of $294,000 to $381,900 savings per year. CONCLUSIONS: TFL has a significantly shorter operative time and decreased cost when compared to the standard Ho:YAG for equivalent kidney stone and patient characteristics. Longer term follow up is needed to see if recurrence rates are affected.

Detection of Salmonella spp. in veterinary samples by combining selective enrichment and real-time PCR.

Rapid screening for enteric bacterial pathogens in clinical environments is essential for biosecurity. Salmonella found in veterinary hospitals, particularly Salmonella enterica serovar Dublin, can pose unique challenges for culture and testing because of its poor growth. Multiple Salmonella serovars including Dublin are emerging threats to public health given increasing prevalence and antimicrobial resistance. We adapted an automated food testing method to veterinary samples and evaluated the performance of the method in a variety of matrices including environmental samples ( n = 81), tissues ( n = 52), feces ( n = 148), and feed ( n = 29). A commercial kit was chosen as the basis for this approach in view of extensive performance characterizations published by multiple independent organizations. A workflow was established for efficiently and accurately testing veterinary matrices and environmental samples by use of real-time PCR after selective enrichment in Rappaport-Vassiliadis soya (RVS) medium. Using this method, the detection limit for S. Dublin improved by 100-fold over subculture on selective agars (eosin-methylene blue, brilliant green, and xylose-lysine-deoxycholate). Overall, the procedure was effective in detecting Salmonella spp. and provided next-day results.

Cytosolic phospholipase A2α regulates G1 progression through modulating FOXO1 activity.

Group IVA phospholipase A2 [cytosolic phospholipase A2α (cPLA2α)] is a key mediator of inflammation and tumorigenesis. In this study, by using a combination of chemical inhibition and genetic approaches in zebrafish and murine cells, we identify a mechanism by which cPLA2α promotes cell proliferation. We identified 2 cpla2α genes in zebrafish, cpla2αa and cpla2αb, with conserved phospholipase activity. In zebrafish, loss of cpla2α expression or inhibition of cpla2α activity diminished G1 progression through the cell cycle. This phenotype was also seen in both mouse embryonic fibroblasts and mesangial cells. G1 progression was rescued by the addition of arachidonic acid or prostaglandin E2 (PGE2), indicating a phospholipase-dependent mechanism. We further show that PGE2, through PI3K/AKT activation, promoted Forkhead box protein O1 (FOXO1) phosphorylation and FOXO1 nuclear export. This led to up-regulation of cyclin D1 and down-regulation of p27(Kip1), thus promoting G1 progression. Finally, using pharmacologic inhibitors, we show that cPLA2α, rapidly accelerated fibrosarcoma (RAF)/MEK/ERK, and PI3K/AKT signaling pathways cooperatively regulate G1 progression in response to platelet-derived growth factor stimulation. In summary, these data indicate that cPLA2α, through its phospholipase activity, is a critical effector of G1 phase progression through the cell cycle and suggest that pharmacological targeting of this enzyme may have important therapeutic benefits in disease mechanisms that involve excessive cell proliferation, in particular, cancer and proliferative glomerulopathies.

Adjuvant therapy of osteosarcoma--A Phase II trial: Southwest Oncology Group study 9139.

BACKGROUND: The objective of this study was to estimate the time to treatment failure and survival rate of the three-drug combination of doxorubicin, cisplatin, and ifosfamide as primary and postoperative, adjunctive treatment for teenagers and adults with osteosarcoma (OS). METHODS: Sixty-three eligible patients with nonmetastatic OS of the extremities were registered from 24 institutions from February, 1992 through December, 1996. Chemotherapy was comprised of doxorubicin at a dose of 75 mg/m2 and cisplatin at a dose of 120 mg/m2, alternating with doxorubicin at a dose of 50 mg/m2 and ifosfamide at a dose of 8 g/m2. Four cycles were given prior to surgical resection, and four cycles were given after surgery. Outcome measures included the time to treatment failure, overall survival, toxicity, and centralized assessment of tumor necrosis. RESULTS: Thirty-one of 63 eligible patients died, for a 5-year overall survival rate of 58% (95% confidence interval [95% CI], 46-71%). The median time to treatment failure was 19 months (95% CI, 12-41 months). A good pathologic response (> or = 90% necrosis) to neoadjuvant chemotherapy was observed in 48% of patients who underwent surgery. There was no correlation noted between response to neoadjuvant chemotherapy and patient outcome. Grade 4 hematologic toxicities were frequent (89%), although serious nonhematologic toxicities other than nausea and emesis were uncommon. CONCLUSIONS: The regimen and schedule used in the current study did not improve outcomes compared with prior trials of doxorubicin and cisplatin alone. New, more effective drugs are needed for the treatment of patients with OS. The identification and utilization of molecular markers to predict outcome and response to therapy would facilitate clinical management, limiting exposure to toxic therapies for patients with favorable molecular profiles and identifying those patients who may fail with current approaches as candidates for clinical trials.

Magnesium-aluminum hydroxide suspension for the treatment of dermal capsaicin exposures.

OBJECTIVES: To determine whether magnesium-aluminum-hydroxide-simethicone suspension (MgAl) is an effective treatment for dermal capsaicin exposures. METHODS: The authors performed a double-blind, randomized, controlled, pilot study comparing the effect of MgAl with that of saline in the treatment of dermal capsaicin exposures. Ten volunteers were sprayed with a commercial defensive spray containing 10% capsaicin on the flexor surface of both forearms. A dressing embedded with MgAl (Maalox) suspension was randomly applied to one arm and a saline-embedded dressing was applied to the other arm. Pain was assessed on a 10-cm visual analog scale at 0, 10, 20, 30, 60, 90, and 120 minutes. RESULTS: Mean pain scores were significantly lower in the MgAl group as compared with the saline (S) group at 10, 20, and 30 minutes. Differences in pain scores were not statistically significant at times 60, 90, and 120 minutes. CONCLUSIONS: During the initial 30 minutes of treatment, there was a statistically significant decrease in pain scores with MgAl as compared with saline treatments. Although the difference in means may have questionable clinical significance, MgAl is cheap and readily available, and has minimal side effects. Thus, MgAl may be an appropriate treatment for dermal capsaicin exposure.