Application of the novel Nalu™ Neurostimulation System for peripheral nerve stimulation.

Peripheral nerve stimulation is an established treatment modality for chronic neuropathic pain. Over the last decade, with the advent of innovative devices and delivery platforms, peripheral nerve stimulation has evolved from invasive open surgeries to image-guided, minimally invasive percutaneous procedures. The authors hereby present a novel device, the Nalu™ Neurostimulation System (Nalu Medical, CA, USA), which has established its advantages in providing predictable and reliable peripheral nerve stimulation therapy for chronic neuropathic pain management. This novel device is effective in treating chronic pain conditions such as post-herniorrhaphy pain syndrome, intercostal neuralgia, post-laminectomy syndrome, and complex regional pain syndrome and holds great promise for the treatment of peripheral neuropathic pain.

Chronic nerve pain is a debilitating condition that can affect quality of life and functioning. The Nalu™ Neurostimulation System (Nalu Medical, CA, USA) provides long-term pain relief without medications. There are numerous devices currently available that can be utilized to block pain signals using small wires. This system is unique because the wires placed over affected nerves are powered by an external battery that does not require permanent surgical implantation. Pain after hernia surgery, back surgery, hip surgery and knee surgery, as well as nerve pain can be effectively managed by this system.

Considerations in permanent implantation of peripheral nerve stimulation (PNS) for chronic neuropathic pain: An international cross-sectional survey of implanters.

AIM: Novel minimally invasive short-term and long-term peripheral nerve stimulation (PNS) systems have revolutionized targeted treatment of chronic neuropathic pain. We present an international survey of PNS-implanting pain physicians to assess what factors they consider when offering permanent PNS. METHODS: This cross-sectional study consisted of a survey (Qualtrics) that was distributed to PNS-implanting physicians in a device supplier's entire email database on November 13, 2020, with 3 weeks of response time. Physicians' contact information in the form of their email addresses had been previously collected by the supplier upon device distribution with permission to use survey responses for research. RESULTS: Of 2032 database physicians, 40 physicians representing 37 institutions responded to the survey. The most common application of PNS was mononeuropathic pain (57%). The most frequently targeted nerve was the suprascapular nerve (29%). 14% of physicians reported 81-100% of their implants were dual-lead. The representative physicians ranged broadly in their most frequently targeted nerves. Although mononeuropathic pain was the most common indication for PNS, there was still varied response regarding other indications such as CRPS and post-surgical chronic pain. CONCLUSION: In context of a low response rate, identifying such factors can help update the prevailing treatment algorithm for interventional therapies, assist pain physicians in better identifying which patients are the best candidates for PNS, and inform future clinical trial design on PNS efficacy.

Preclinical characterization of AB-506, an inhibitor of HBV replication targeting the viral core protein.

AB-506, a small-molecule inhibitor targeting the HBV core protein, inhibits viral replication in vitro (HepAD38 cells: EC50 of 0.077 µM, CC50 > 25 µM) and in vivo (HBV mouse model: ∼3.0 log10 reductions in serum HBV DNA compared to the vehicle control). Binding of AB-506 to HBV core protein accelerates capsid assembly and inhibits HBV pgRNA encapsidation. Furthermore, AB-506 blocks cccDNA establishment in HBV-infected HepG2-hNTCP-C4 cells and primary human hepatocytes, leading to inhibition of viral RNA, HBsAg, and HBeAg production (EC50 from 0.64 µM to 1.92 µM). AB-506 demonstrated activity across HBV genotypes A-H and maintains antiviral activity against nucleos(t)ide analog-resistant variants in vitro. Evaluation of AB-506 against a panel of core variants showed that T33N/Q substitutions results in >200-fold increase in EC50 values, while L30F, L37Q, and I105T substitutions showed an 8 to 20-fold increase in EC50 values in comparison to the wild-type. In vitro combinations of AB-506 with NAs or an RNAi agent were additive to moderately synergistic. AB-506 exhibits good oral bioavailability, systemic exposure, and higher liver to plasma ratios in rodents, a pharmacokinetic profile supporting clinical development for chronic hepatitis B.