Induction of antiviral interferon-stimulated genes by neuronal STING promotes the resolution of pain in mice.

Inflammation and pain are intertwined responses to injury, infection, or chronic diseases. While acute inflammation is essential in determining pain resolution and opioid analgesia, maladaptive processes occurring during resolution can lead to the transition to chronic pain. Here we found that inflammation activates the cytosolic DNA-sensing protein stimulator of IFN genes (STING) in dorsal root ganglion nociceptors. Neuronal activation of STING promotes signaling through TANK-binding kinase 1 (TBK1) and triggers an IFN-ß response that mediates pain resolution. Notably, we found that mice expressing a nociceptor-specific gain-of-function mutation in STING exhibited an IFN gene signature that reduced nociceptor excitability and inflammatory hyperalgesia through a KChIP1-Kv4.3 regulation. Our findings reveal a role of IFN-regulated genes and KChIP1 downstream of STING in the resolution of inflammatory pain.

Postoperative Scar Management Protocol for Asian Patients.

BACKGROUND: Postoperative scar formation remains a morbidity for patients even with the advent of minimally invasive techniques. Furthermore, the significant difference between the Asian and Caucasian skin results in poorer postoperative scar outcomes in Asians, supporting the need for an evidence-based scar management protocol. METHODS: Following a literature review of the PubMed and the Cochrane databases over the past 10 years, we constructed a novel postoperative scar management protocol for the Asian skin, utilized in a Singaporean tertiary healthcare institution. RESULTS: We describe a timeline-based scar protocol from the point of skin closure to a minimum of 1 year of follow-up. We support the use of intraoperative botulinum toxin for selected high-risk individuals upon skin closure with a follow-up regimen in the postoperative setting. For recalcitrant keloids, we have described a multimodal therapy comprising elements of intralesional steroids, botulinum toxin, lasers, surgery, and radiotherapy. CONCLUSIONS: A consolidated postoperative scar management protocol provides the necessary guidance for improved scar outcomes in the Asian skin. There is inherent potential in expanding the protocol to include post-traumatic and burn wounds or support other skin types including the Caucasian skin. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Conventional oral and secondary high dose vaginal metronidazole therapy for recurrent bacterial vaginosis: clinical outcomes, impacts of sex and menses.

PURPOSE: Oral metronidazole therapy is the standard of care for bacterial vaginosis (BV), yet it has alarming rates of recurrence and refractory responses among recurrent BV (RBV) patients. This study addresses whether high dose vaginal metronidazole therapy (HDM) is beneficial in RBV patients who fail after standard of care (SOC) therapy, whether diagnostic test scores proximal to the HDM predict clinical outcome, and whether menses, coitus, or race influences therapy outcome. PATIENTS AND METHODS: A total of 90 patients with RBV were given SOC and tracked 74 for up to 9 months. Refractory or recurrent patients (57) with symptomatic BV were given HDM and followed for up to 8 months. Patients were evaluated by Amsel criteria, Nugent score, and a qPCR assay that assesses the Lactobacillus content. RESULTS: HDM achieved at least short-term remission in 68% of the patients who were refractory to or recurred after SOC and provided a 10-day increase in the mean duration of remission among patients who eventually recurred (p=0.027). Patients with prolonged dysbiosis (pH >5 or Amsel 4) before symptomatic recurrence were more likely to recur after subsequent HDM. Most recurrence happened within 10 days of menses, but sex in this cohort was not associated with clinical outcome. Mean diagnostic BV scores of African American patients in remission were inferior to scores of a small cohort of Caucasian patients in remission. CONCLUSION: Encouraging results obtained with HDM justify a prospective, randomized study to determine if follow-up HDM is beneficial among a broader cohort of women failing conventional oral metronidazole therapy.

Prognostic Indicators of Recurrence of Bacterial Vaginosis.

Following all forms of therapy for bacterial vaginosis (BV), recurrence rates are extremely high. Many diagnostic tests are available that differentiate bacterial vaginosis from other types of vaginal disorders, but none predict recurrence after treatment, nor are any vetted for monitoring ongoing responses to treatment. Our goal was to determine which tests, and at what optimal times, have prognostic value in predicting recurrence. This prospective cohort study monitored 74 highly recurrent BV patients for up to 9 months. Symptomatic BV patients were treated with oral metronidazole and were evaluated at cessation of treatment and monthly. Index tests included Amsel, Nugent, BV Blue, and Affirm VPIII, as well as a quantitative PCR (qPCR)-based test under initial evaluation here. The qPCR-based LbRC ( LactobacillusRelative Composition) assay predicted BV recurrence when performed shortly after oral metronidazole treatment, with both 90% positive predictive values (PPV) and 74% negative predictive values (NPV); the Nugent scores had 93% PPV but poor NPV (57%). No test, at any other visit, was prognostic. The LbRC assay and, to a lesser extent, Nugent tests scored a week after oral metronidiazole predicted recurrence, suggesting that the recurrence in this cohort was predominantly by relapse due to incomplete restoration of eubiosis soon after therapy. This is the first study in an under evaluated population of recurrent BV patients that emphasizes the need for and a pathway to a possible prognostic modality. Given the high recurrence rates of BV, prognostic tests that could influence individualized treatment alternatives are urgently needed.