Technetium-99m-SM3(Xanthus Pharmaceuticals, Inc.)

Background Ureteropelvic junction stenosis (UPJS) is the most common cause of clinically significant antenatal hydronephrosis. We compared separate renal function results obtained using technetium-99m-mercaptoacetyltriglycine (Tc-99m MAG-3) and technetium-99m-dimercaptosuccinic acid (Tc-99m DMSA) in pediatric patients with UPJS to evaluate the adequacy of Tc-99m MAG-3 scintigraphy and the necessity of additional Tc-99m DMSA scintigraphy during follow-up. Methodology Patients diagnosed with hydronephrosis in the Pediatric Nephrology Department of Pamukkale University Faculty of Medicine over a period of 10 years (2012-2022) were evaluated retrospectively. Patients who had been diagnosed with UPJS and underwent both Tc-99m MAG-3 and Tc-99m DMSA scintigraphy during follow-up were included in the study. Technetium-99m-labeled MAG-3 and DMSA scans were re-evaluated for all patients by the Department of Nuclear Medicine. Results The study included 52 children with unilateral UPJS (12 girls and 40 boys) with a mean age of 6.34 ± 4.81 years (range: 2.97-9.79 years). Thirty-six patients (69.2%) were diagnosed antenatally. Differential renal function in Tc-99m DMSA was 46.94 ± 10.64 and in Tc-99m MAG-3 was 43.08 ± 11.18; the functions were lower in Tc-99m MAG-3, but the values were within normal limits for both groups (p=0.0001, z=-3.893). When differential renal functions were compared between Tc-99m DMSA and Tc-99m MAG-3 results, a statistically significant positive and strong correlation was found in the kidney with ureteropelvic junction obstruction (UPJO) (p=0.0001, r=0.752). When classifying the Tc-99m MAG-3 and Tc-99m DMSA results in the kidney with UPJO (supranormal, normal, low function) for the determination of differential renal functions, there was a consistency of 76%, and it was correlated (p=0.0001, k=0.456). While two patients had supranormal function and 13 patients had low function in Tc-99m MAG-3, five patients had supranormal function, and eight patients had low function in Tc-99m DMSA. Conclusions Some studies in the literature have reported that Tc-99m MAG-3 causes supranormal function measurements in patients with UPJS; our results showed that Tc-99m DMSA resulted in a higher rate of supranormal values for affected kidneys. We believe that Tc-99m DMSA should not be performed in addition to Tc-99m MAG-3 scintigraphy in the follow-up of every patient with UPJS but can be utilized in select cases, such as patients with surgical indications and those suspected before surgery.

Bacterial swarming, a collective movement on a surface, has rarely been associated with human pathophysiology. This study aims to define a role for bacterial swarmers in amelioration of intestinal stress.

We developed a polymicrobial plate agar assay to detect swarming and screened mice and humans with intestinal stress and inflammation. From chemically induced colitis in mice, as well as humans with inflammatory bowel disease, we developed techniques to isolate the dominant swarmers. We developed swarm-deficient but growth and swim-competent mutant bacteria as isogenic controls. We performed bacterial reinoculation studies in mice with colitis, fecal 16S, and meta-transcriptomic analyses, as well as in vitro microbial interaction studies.

We show that bacterial swarmers are highly predictive of intestinal stress in mice and humans. We isolated a novel Enterobacter swarming strain, SM3, from mouse feces. SM3 and other known commensal swarmers, in contrast to their mutant strains, abrogated intestinal inflammation in mice. Treatment of colitic mice with SM3, but not its mutants, enriched beneficial fecal anaerobes belonging to the family of Bacteroidales S24-7. We observed SM3 swarming associated pathways in the in vivo fecal meta-transcriptomes. In vitro growth of S24-7 was enriched in presence of SM3 or its mutants; however, because SM3, but not mutants, induced S24-7 in vivo, we concluded that swarming plays an essential role in disseminating SM3 in vivo.

Overall, our work identified a new but counterintuitive paradigm in which intestinal stress allows for the emergence of swarming bacteria; however, these bacteria act to heal intestinal inflammation.