Case report: Dorsal root ganglion stimulator lead fracture.

BACKGROUND: One of the unique advances in neuromodulation for chronic pain has been spinal cord stimulators (SCS) and dorsal root ganglion stimulators (DRG-S). These devices have aided in conditions such as neuropathic pain, complex regional pain syndromes, failed back surgery, and peripheral neuropathies. With these benefits, however, complications from implantable stimulators have included lead fractures and migration. The authors reviewed a lead migration, kinking, and subsequent fracture event involving a patient with complex regional pain syndrome (CRPS) II, who was treated with a DRG-S. CASE PRESENTATION: The case report follows this patient, from their past medical history to assessment of appropriate qualifications for neuromodulation, to successful surgical placement, to follow-up care. The authors further monitored assessment of inefficacy of pain relief, and identification of lead migration and kinking through imaging. In the process of removal, due to lead stress, lead fracturing occurred. After lead removal, the leads were fully replaced, and the patient was followed up and experienced improved pain relief. CONCLUSION: The case report assesses probable mechanisms of lead fracture and considerations for physicians for future assessment and triage of neuromodulation efficacy.

Opioids after a cesarean section: Prescribing, patient use, storage, and disposal practices.

Cesarean sections (C-sections) are commonly performed procedures, accounting for approximately one-third of births in the United States. This is often one of the first medical encounters for women which require prescription medications to manage post-operative pain. Our observational study looked at opioids prescribed and consumed for post-surgical C-section pain. We interviewed patients to examine handling practices of those who had excess opioids, including storage and disposal. Patients underwent a C-section at Duke University Health System from January 2017 through July 2018 and were pre-scribed opioids post-operatively. In this study, we observed 154 women who met inclusion criteria. Sixty women declined participation, and 15 could not recall the details of their opioid use. Of the 77 women who participated, most (97 percent) received oxycodone 5 mg tablets. About one-third of the women did not use any opioids, about one-third used all of their opioids, and the remainder used only a fraction of the pills prescribed. After sharing preliminary results with providers, they began prescribing fewer pills. Even then, only a fraction or none of the pills were used, and patients rarely required a renewal of pain prescriptions. We found only 1 percent of women stored their opioids in a secure location. These findings suggest an individualized approach to opioid prescribing along with nonopioid analgesics use may mitigate the consequences of excess opioid prescribing, which include lack of proper disposal and excess opioids in the community.

Multidisciplinary simulation of local anaesthetic systemic toxicity improves diagnostic and treatment skills and self-confidence for pain clinic procedural staff.

Local anaesthetic systemic toxicity (LAST) is a rare complication after outpatient interventional pain procedures, which can present as an emergent and life-threatening condition. Proficiency and confidence in managing this rare situation necessitates strategies to ensure team members can perform necessary tasks. The primary objective was to familiarse the pain clinic procedural staff-physicians, nurses, medical assistants, and radiation technologists-with concise and current instruction and an opportunity to practice in a controlled environment. A two-part series was designed and led by the pain physicians, with the assistance of the simulation centre and clinic staff. A 20 min didactic session was held to familiarise the providers with relevant details and information regarding LAST. Then, 2 weeks later, all team members participated in a simulation exercise intended to portray a LAST encounter, tasking participants to recognise and manage the condition in a team-based model. Before and after the didactic and simulation sessions, the staff was administered a questionnaire to assess knowledge of LAST signs, symptoms, management strategies, and priorities. Respondents were better able to identify signs and symptoms of toxicity and prioritise management steps, and felt more confident in recognising symptoms, starting treatment and coordinating care. Furthermore, participants emphasised the positive of debriefing, practicing a rare situation and learning strategies for effective communication, team dynamics and role clarity. FORMAT: Small group didactic session, simulation exercise in a clinical simulation lab. TARGET AUDIENCE: Attending, fellow, and resident physicians, medical students, registered nurses, certified medical assistants, and radiation technologists working in a pain clinic procedure suite. OBJECTIVES: To acquaint the pain clinic procedural staff with current training related to LAST and an opportunity to practice in a controlled environment.

A novel use of an artificially intelligent Chatbot and a live, synchronous virtual question-and answer session for fellowship recruitment.

INTRODUCTION: Academic departments universally communicate information about their programs using static websites. In addition to websites, some programs have even ventured out into social media (SM). These bidirectional forms of SM interaction show great promise; even hosting a live Question and Answer (Q&A) session has the potential for program branding. Artificial Intelligence (AI) usage in the form of a chatbot has expanded on websites and in SM. The potential use of chatbots, for the purposes of trainee recruitment, is novel and underutilized. With this pilot study, we aimed to answer the question; can the use of an Artificially Intelligent Chatbot and a Virtual Question-and-Answer Session aid in recruitment in a Post-COVID-19 era? METHODS: We held three structured Question-and-Answer Sessions over a period of 2 weeks. This preliminary study was performed after completion of the three Q&A sessions, in March-May, 2021. All 258 applicants to the pain fellowship program were invited via email to participate in the survey after attending one of the Q&A sessions. A 16-item survey assessing participants' perception of the chatbot was administered. RESULTS: Forty-eight pain fellowship applicants completed the survey, for an average response rate of 18.6%. In all, 35 (73%) of survey respondents had used the website chatbot, and 84% indicated that it had found them the information they were seeking. CONCLUSION: We employed an artificially intelligent chatbot on the department website to engage in a bidirectional exchange with users to adapt to changes brought on by the pandemic. SM engagement via chatbot and Q&A sessions can leave a favorable impression and improve the perception of a program.

Antibody-Exatecan Conjugates with a Novel Self-immolative Moiety Overcome Resistance in Colon and Lung Cancer.

Antibody-drug conjugates (ADC) using DNA topoisomerase I inhibitor DXd/SN-38 have transformed cancer treatment, yet more effective ADCs are needed for overcoming resistance. We have designed an ADC class using a novel self-immolative T moiety for traceless conjugation and release of exatecan, a more potent topoisomerase I inhibitor with less sensitivity to multidrug resistance (MDR). Characterized by enhanced therapeutic indices, higher stability, and improved intratumoral pharmacodynamic response, antibody-T moiety-exatecan conjugates targeting HER2, HER3, and TROP2 overcome the intrinsic or treatment resistance of equivalent DXd/SN-38 ADCs in low-target-expression, large, and MDR+ tumors. T moiety-exatecan ADCs display durable antitumor activity in patient-derived xenograft and organoid models representative of unmet clinical needs, including EGFR ex19del/T790M/C797S triple-mutation lung cancer and BRAF/KRAS-TP53 double-mutant colon cancer, and show synergy with PARP/ATR inhibitor and anti-PD-1 treatment. High tolerability of the T moiety-exatecan ADC class in nonhuman primates supports its potential to expand the responding patient population and tumor types beyond current ADCs. SIGNIFICANCE: ADCs combining a novel self-immolative moiety and topoisomerase I inhibitor exatecan as payload show deep and durable response in low-target-expressing and MDR+ tumors resistant to DXd/SN-38 ADCs without increasing toxicity. This new class of ADCs has the potential to benefit an additional patient population beyond current options. See related commentary by Gupta et al., p. 817. This article is highlighted in the In This Issue feature, p. 799.

Sympathetic Blocks for Visceral Pain.

For patients with chronic pain or cancer-related pain, the most common indication for sympathetic block is to control visceral pain arising from malignancies or other alterations of the abdominal and pelvic viscera. When it is recalcitrant to conservative care, or if the patient is intolerant to pharmacotherapy, consideration of sympathetic blocks or neurolytic procedures is considered. Potential advantages of a neurolytic procedure, compared with spinal and epidural anesthetic infusions, include cost savings and avoidance of hardware. Interventional therapies that target afferent visceral innervation via the sympathetic ganglia offer effective and durable analgesia and improve multiple metrics of quality of life.

Opioid Induced Hyperalgesia.

OBJECTIVE: To discuss the phenomenon of opioid induced hyperalgesia (OIH) and investigate the data and clinical recommendations available on this topic. DESIGN: A literature search on the topic of OIH was performed. Relevant studies pertaining to OIH were included in this review. RESULTS: Existing studies and reviews on the pathophysiology, diagnosis, and clinical management of OIH are discussed with updated data and literature references. CONCLUSION: As more opioids are prescribed, especially to treat chronic nonmalignant pain, OIH becomes more of a relevant and significant issue. Although the exact mechanisms of OIH are not clearly understood further research is required to broaden and develop our knowledge of this topic.

Aberrant behaviors in a primary care-based cohort of patients with chronic pain identified as misusing prescription opioids.

OBJECTIVE: To assess aberrant drug-related behaviors (ADRBs) in patients discharged from a community primary care practice for opioid misuse and treating physician's ability to identify predictive aberrant behaviors. DESIGN: Retrospective chart review of patients with chronic noncancer pain (CNCP) identified by their treating physician as misusing opioid analgesics, and patients with similar characteristics who had not been identified as misusing opioids. A survey of attending and resident physicians from these clinics on their knowledge of ADRBs was also collected. SETTING: Community primary care clinic. PATIENTS, PARTICIPANTS: Thirty-three patients with CNCP identified by their treating physician as misusing prescription opioid analgesics, and 33 patients randomly selected from the same clinic setting, with similar characteristics who had not been identified as misusing opioids. Twenty-four attending physicians and 42 resident physicians were surveyed on their training and knowledge of predictive aberrant behaviors. RESULTS: More identified misusers than nonmisusers reported positive history of substance abuse (p=0.001), tobacco use (p=0.011), taking multiple doses of prescribed opioids together (0.024), multiple complaints of pain requiring opioid treatment (p=0.006), and multiple phone calls to the clinic requesting opioid medications (p=0.027). Logistic regression on continuous variables revealed that only the number of phone calls to the clinic regarding opioids in the last 12 months achieved significance (p=0.028). CONCLUSIONS: Previously postulated and novel ADRBs suggestive of opioid misuse were identified in a community primary care setting. Differences in resident and attending physician's ability to identify key predictive ADRBs and lack of training in pain or addiction underscores the need for changes in medical school and residency programs.

Heterogeneity of receptor function in colon carcinoma cells determined by cross-talk between type I insulin-like growth factor receptor and epidermal growth factor receptor.

This study identifies a novel cross-talk paradigm between the type I insulin-like growth factor receptor (IGF1R) and epidermal growth factor receptor (EGFR) in colon cancer cells. IGF1R activation by ligand exposure in growth factor-deprived cells induces Akt activation in the FET, CBS, and GEO colon cancer cell lines. Investigation of IGF1R-mediated signaling pathways using small interfering RNA approaches indicated that, as expected, phosphatidylinositol 3'-kinase (PI3K) was activated by IGF1R. Mitogen-activated protein kinase (MAPK) activity as reflected by phospho-extracellular signal-regulated kinase (ERK) induction was not significantly activated until later times following release of these cells from growth factor deprivation stress. The appearance of phospho-ERK was proximal to EGFR activation. Treatment of cells with the PI3K inhibitor LY294002 before release from stress resulted in a concentration-dependent loss of EGFR activation, whereas treatment with the MAPK inhibitor PD98059 did not block EGFR activation, indicating that EGFR activation was downstream of the IGF1R/PI3K pathway. PD98059 inhibition of MAPK was associated with a concentration-dependent reduction in EGFR-mediated phospho-ERK. EGFR inhibitor blocked induction of phospho-ERK, showing that MAPK activity was a consequence of EGFR-mediated signaling. On the other hand, a small-molecule IGF1R inhibitor, PQIP, blocked Akt phosphorylation. The divergent signaling functions of IGF1R and EGFR suggested the potential for synergism by a combination of therapy directed at the two receptors. Combination treatment with PQIP and EGFR inhibitor Tarceva resulted in synergistic effects as indicated by combination index analysis in all three cell lines tested.

Reorganization of ErbB family and cell survival signaling after Knock-down of ErbB2 in colon cancer cells.

The role of the ErbB family in supporting the malignant phenotype was characterized by stable transfection of a single chain antibody (ScFv5R) against ErbB2 containing a KDEL endoplasmic reticulum retention sequence into GEO human colon carcinoma cells. The antibody traps ErbB2 in the endoplasmic reticulum, thereby down-regulating cell surface ErbB2. The transfected cells showed inactivation of ErbB2 tyrosine phosphorylation and reduced heterodimerization of ErbB2 and ErbB3. This resulted in greater sensitivity to apoptosis induced by growth deprivation and delayed tumorigenicity in vivo. Furthermore, decreased heterodimerization of ErbB2 and ErbB3 led to a reorganization in ErbB function in transfected cells as heterodimerization between epidermal growth factor receptor (EGFR) and ErbB3 increased, whereas ErbB3 activation remained almost the same. Importantly, elimination of ErbB2 signaling resulted in an increase in EGFR expression and activation in transfected cells. Increased EGFR activation contributed to the sustained cell survival in transfected cells.