Quantifying the transcriptomic ratios MMP8/HLA-DRA, LCN2/HLA-DRA by ddPCR is a promising approach to improve sepsis diagnosis in surgical patients.

Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA-DRA expression was quantified using droplet digital PCR, a next-generation PCR technology. Area under the receiver operating curve analysis (AUROC) showed that the PCT/HLA-DRA ratio outperformed PCT to detect sepsis (AUROC [CI95%], p): PCT: 0.80 [0.73–0.88], <0.001; PCT/HLA-DRA: 0.85 [0.78–0.91], <0.001. In the multivariate analysis, the ratio showed a superior ability to predict sepsis compared to that of PCT (OR [CI 95%], p): PCT/HLA-DRA: 7.66 [1.82–32.29], 0.006; PCT: 4.21 [1.15–15.43] 0.030. Multivariate analysis was confirmed using a new surgical cohort with 74 sepsis patients and 21 controls: PCT/HLA-DRA: 34.86 [1.22–995.08], 0.038; PCT: 5.52 [0.40–75.78], 0.201. In conclusion, the combination of PCT with HLA-DRA is a promising strategy for improving sepsis detection in surgical patients.

Bisphosphonates such as pamidronate are widely used in the treatment of patients with lytic bony lesions secondary to breast cancer or multiple myeloma, yet they have been associated with deterioration of renal function and histopathological changes in the kidney. There have been recent reports associating the use of pamidronate with the development of the collapsing variant of focal segmental glomerulosclerosis (CFSGS), a rapidly progressive variant of focal segmental glomerulosclerosis that leads to end-stage renal disease. We describe five patients who developed worsening renal function, proteinuria, and nephrotic syndrome while taking pamidronate; three of them had biopsy-proven CFSGS. Pamidronate was discontinued, and a longitudinal follow-up was performed for 10 to 23 months. One patient was able to discontinue hemodialysis, and all patients experienced improvement in renal function and a decrease in proteinuria. In some patients who develop pamidronate-associated CFSGS, renal damage appears to be reversible if the syndrome is recognized early and pamidronate is stopped.

Fibromuscular dysplasia is a rare nonatherosclerotic, noninflammatory angiopathy of uncertain etiology and high morbidity. Because of its propensity to affect medium-sized vessels in a variety of locations, presenting symptoms may vary substantially, resulting in a delayed or missed diagnosis. We describe a 57-year-old woman who, on multiple occasions, presented with progressive gastrointestinal symptoms and eventually underwent surgical revascularization for celiac and superior mesenteric artery stenosis of uncertain etiology. Her postoperative course was complicated by bowel ischemia, multiple organ failure, and death. Autopsy findings proved useful in determining the underlying disease process and cause of death. This case report and a review of the literature illustrate the high morbidity and mortality that are caused by mesenteric fibromuscular dysplasia, the challenge in establishing a correct diagnosis, and the importance of early detection and treatment.

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