Oxytocin and Related Peptide Hormones: Candidate Anti-Inflammatory Therapy in Early Stages of Sepsis.

Sepsis is a potentially life-threatening systemic inflammatory syndrome characterized by dysregulated host immunological responses to infection. Uncontrolled immune cell activation and exponential elevation in circulating cytokines can lead to sepsis, septic shock, multiple organ dysfunction syndrome, and death. Sepsis is associated with high re-hospitalization and recovery may be incomplete, with long term sequelae including post-sepsis syndrome. Consequently, sepsis continues to be a leading cause of morbidity and mortality across the world. In our recent review of human chorionic gonadotropin (hCG), we noted that its major properties including promotion of fertility, parturition, and lactation were described over a century ago. By contrast, the anti-inflammatory properties of this hormone have been recognized only more recently. Vasopressin, a hormone best known for its anti-diuretic effect, also has anti-inflammatory actions. Surprisingly, vasopressin's close cousin, oxytocin, has broader and more potent anti-inflammatory effects than vasopressin and a larger number of pre-clinical studies supporting its potential role in limiting sepsis-associated organ damage. This review explores possible links between oxytocin and related octapeptide hormones and sepsis-related modulation of pro-inflammatory and anti-inflammatory activities.

Human Chorionic Gonadotropin and Related Peptides: Candidate Anti-Inflammatory Therapy in Early Stages of Sepsis.

Sepsis continues to be a major cause of morbidity, mortality, and post-recovery disability in patients with a wide range of non-infectious and infectious inflammatory disorders, including COVID-19. The clinical onset of sepsis is often marked by the explosive release into the extracellular fluids of a multiplicity of host-derived cytokines and other pro-inflammatory hormone-like messengers from endogenous sources ("cytokine storm"). In patients with sepsis, therapies to counter the pro-inflammatory torrent, even when administered early, typically fall short. The major focus of our proposed essay is to promote pre-clinical studies with hCG (human chorionic gonadotropin) as a potential anti-inflammatory therapy for sepsis.

Case Report and Supporting Documentation: Acute Kidney Injury Manifested as Oliguria Is Reduced by Intravenous Magnesium Before Cisplatin.

After more than four decades of post-approval, cisplatin is still an important treatment for numerous cancers. However, acute kidney injury (AKI), defined as significant impairment of renal filtration as discussed below, is the major limiting side effect of cisplatin, occurring in approximately 30% of patients (25-33% after the first course). Cisplatin also damages the kidneys' ability to reabsorb magnesium in 40-100% of patients, with collateral health risks due to subsequent hypomagnesemia. Multiple methods and drugs have been proposed for preventing cisplatin-induced AKI, including saline infusion with or without mannitol, which has not always prevented AKI and has been found to activate a cellular stress response in renal tubular cells. While numerous reports and trials, as well as the National Comprehensive Cancer Network (NCCN), support premedication with magnesium and hydration, this practice has not been universally accepted. Many clinics administer intravenous magnesium (IV) only after identification of hypomagnesemia post-cisplatin treatment, thus placing patients at risk for AKI and chronic renal loss of magnesium. We present the following case report and additional supporting evidence identifying the immediate effect of IV magnesium prior to intraperitoneal cisplatin for cycle 4 because of documented hypomagnesemia resulting in normalization of oliguria, which had been experienced for the first three cycles. The patient subsequently requested and received IV magnesium before cisplatin for the next two cycles with continuation of normal urinary output. The effect of pretreatment with IV magnesium on urine output following cisplatin has not been previously reported and further supports pre-cisplatin administration. In addition, two recent meta-analyses of clinical trials and pre-clinical research are reviewed that demonstrate effectiveness of magnesium pretreatment to preventing AKI without reducing its chemotherapeutic efficacy. This case report with additional evidence supports the adoption of administration of 1-3 g IV magnesium before cisplatin as best practice to prevent cisplatin induced AKI and hypomagnesemia regardless of patient baseline serum magnesium levels.

Sacral nerve stimulation reduces elevated urinary nerve growth factor levels in women with symptomatic detrusor overactivity.

OBJECTIVES: To investigate changes in urinary nerve growth factor (uNGF) in women with symptomatic detrusor overactivity (DO) following peripheral nerve evaluation (PNE) for sacral neuromodulation vs controls. STUDY DESIGN: There were 23 subjects with overactive bladder symptoms and DO who failed management with anticholinergics and 22 controls consented to participate in this prospective pilot study. Urine specimens were collected from controls at baseline for evaluation of uNGF and creatinine. Subjects were evaluated at baseline and 5 days after a trial of sacral nerve stimulation referred to as a PNE. Each visit included urine collection for uNGF and, Incontinence Quality of Life Questionnaire, Urinary Distress Inventory Questionnaire, postvoid residual volume, and a 3-day voiding diary. uNGF levels were measured by enzyme-linked immunosorbent assay and expressed as uNGF pg/creatinine mg. RESULTS: Subjects with DO had significantly higher baseline uNGF levels (corrected for creatinine) compared with controls (19.82 pg/mg vs 7.88 pg/mg, P < .002). Seventeen DO subjects underwent PNE and were evaluated at the end of the testing period. There was a significant improvement in quality of life scores for subjects after PNE compared with baseline (Urinary Distress Inventory Questionnaire: 7.0 vs 13.7, P < .001; Incontinence Quality of Life Questionnaire: 87.3 vs 52.8, P < .0001). Concordantly, uNGF levels significantly decreased from 17.23 pg/mg to 9.24 pg/mg (P < .02) after PNE. CONCLUSION: uNGF levels decrease with symptomatic response in DO subjects undergoing PNE. DO subjects had significantly higher uNGF at baseline vs controls, and uNGF levels significantly decreased after only 5 days of sacral nerve stimulation. These findings support a larger study to validate the use of uNGF as an objective tool to assess therapeutic outcome in patients undergoing PNE for sacral neuromodulation.