Rejected

Peripheral nerve injury can result in debilitating outcomes including loss of function and neuropathic pain. Although nerve repair research and therapeutic development are widely studied, translation of these ideas into clinical interventions has not occurred at the same rate. At the turn of this century, approaches to peripheral nerve repair have included microsurgical techniques, hollow conduits, and autologous nerve grafts. These methods provide satisfactory results; however, they possess numerous limitations that can prevent effective surgical treatment. Commercialization of Avance, a processed nerve allograft, sought to address limitations of earlier approaches by providing an off-the-shelf alternative to hollow conduits while maintaining many proregenerative properties of autologous grafts. Since its launch in 2007, Avance has changed the landscape of the nerve repair market and is used to treat tens of thousands of patients. Although Avance has become an important addition to surgeon and patient clinical options, the product's journey from bench to bedside took over 20 years with many research and commercialization challenges. This article reviews the events that have brought a processed nerve allograft from the laboratory bench to the patient bedside. Additionally, this review provides a perspective on lessons and considerations that can assist in translation of future medical products.

The pregnancy and lactation-associated osteoporosis (PLO) is a rare disease whose precise pathophysiological mechanisms remain mostly unknown.

Reticular erythematous mucinosis (REM syndrome) is a rare skin disease that predominantly affects women. It is clinically characterized by flat, partly reticular, irregularly configurated pale erythema located in the region of the central chest and upper back. The skin alterations are usually asymptomatic or associated with slight pruritus or burning. Extracutaneous diseases and involvement of internal organs do not occur in REM syndrome. Histopathological features include perivascular and periadnexal lymphocytic inflammatory infiltrates as well as increased deposition of mucin in the dermis. Due to the similar histology to lupus erythematosus (LE) tumidus, it is discussed whether REM syndrome can be assigned to the spectrum of cutaneous LE or can be assessed as a lupus-like disease. Moreover, both conditions respond well to treatment with hydroxychloroquine.

Transarterial chemoembolization (TACE) is a common treatment for unresectable hepatocellular carcinoma (HCC). The most common complications after TACE are non-specific symptoms called post-embolization syndrome, such as abdominal pain or fever. Rare complications, such as liver failure, liver abscess, sepsis, pulmonary embolism, cholecystitis, can also occur. On the other hand, gallbladder perforation is quite rare. This paper reports a case of gallbladder perforation following TACE. A 76-year-old male with a single 9-cm-sized HCC underwent TACE. Five days after TACE, he developed persistent right upper quadrant pain and ileus. An abdomen CT scan confirmed gallbladder perforation with bile in the right paracolic gutter and pelvic cavity. Percutaneous transhepatic gallbladder drainage was performed with the intravenous administration of antibiotics. After 1 month, the patient underwent right hemihepatectomy and cholecystectomy. Physicians should consider the possibility of gallbladder perforation, which is a rare complication after TACE, when unexplained abdominal pain persists.

Acupuncture has been used to treat a variety of illness and involves the insertion and manipulation of needles into specific points on the body (termed "acupoints"). It has been suggested that acupoints are not merely discrete, static points, but can be dynamically changed according to the pathological state of internal organs. We investigated in a rat model of mustard oil (MO)-induced visceral hyperalgesia whether the number and size of acupoints were modified according to the severity of the colonic pain, and whether the changes were associated with enhanced activity of the spinal dorsal horn. In MO-treated rats, acupoints showing neurogenic inflammation (termed "neurogenic spots" or Neuro-Sps) were found both bilaterally and unilaterally on the leg. The number and size of these acupoints increased along with increasing doses of MO. Electroacupuncture of the acupoints generated analgesic effects on MO-induced visceral hypersensitivity. The MO-treated rats showed an increase in c-Fos expression in spinal dorsal horn neurons and displayed increased evoked activity and a prolonged after-discharge in spinal wide dynamic response (WDR) neurons in response to colorectal distension. Increased number and size of neurogenic inflammatory acupoints following MO treatment were reduced by inhibiting AMPA and NMDA receptors in the spinal cord. Our findings suggest that acupoints demonstrate increased number and size along with severity of visceral pain, which may be associated with enhanced neuronal responses in spinal dorsal horn neurons.

To reduce the individual, societal, and economic burden of the high sick leave rates due to chronic pain, it is essential to find effective strategies for increasing return to work (RTW). Although multimodal rehabilitation programs (MMRPs) may have positive effects on RTW, the results are inconsistent. This study explores the factors that contribute to decreasing sick leave and increasing RTW in patients with chronic pain who completed a MMRP. Four focus groups and three individual interviews were conducted. In total, 18 patients were interviewed. All patients had chronic pain and had completed a MMRP. They were either employed or unemployed, either working to some degree or fully on sick leave. The data were analysed using qualitative content analysis. Three main categories were identified: Knowledge and understanding-prerequisites for tailored solutions; Individual adaptations-necessary but difficult to implement; and Stakeholder collaboration-needs improvement. The participants described a variety of facilitating and limiting factors that created complex prerequisites for RTW. This finding makes it clear that these patients need tailored interventions and strong collaboration among all stakeholders throughout the rehabilitation process. Tailored interventions and collaborations could improve the effectiveness of MMRPs.IMPLICATIONS FOR REHABILITATIONPatients with chronic pain need tailored solutions and adaptations based on their individual needs in the RTW rehabilitation process.To return to work, patients with chronic pain needs support to strengthen their selfconfidence and to be prepared with knowledge and strategies about their abilities and their rights and obligations in relation to the labour market.A well-designed and communicated RTW rehabilitation plan supports the patient in the RTW rehabilitation process.To improve the possibility for employees and employers to create a sustainable work situation, stakeholder reconciliation meetings should be held routinely over time to strengthen the transfer of knowledge and collaboration.

Macrophages play critical roles in homeostasis and inflammation. Macrophage polarization to either a pro-inflammatory or anti-inflammatory status is controlled by activating inflammatory signaling pathways. Ubiquitination is a post-translational modification that regulates these inflammatory signaling pathways. However, the influence of protein ubiquitination on macrophage polarization has not been well studied. We hypothesized that the ubiquitination status of key proteins in inflammatory pathways contributes to macrophage polarization, which is regulated by itchy E3 ubiquitin ligase (ITCH), a negative regulator of inflammation. Using ubiquitin proteomics, we found that ubiquitination profiles are different among polarized murine macrophage subsets. Interestingly, interleukin-1α (IL-1α), an important proinflammatory mediator, was specifically ubiquitinated in lipopolysaccharide-induced proinflammatory macrophages, which was enhanced in ITCH-deficient macrophages. The ITCH-deficient macrophages had increased levels of the mature form of IL-1α and exhibited proinflammatory polarization, and reduced deubiquitination of IL-1α protein. Finally, IL-1α neutralization attenuated pro-inflammatory polarization of the ITCH-deficient macrophages. In conclusion, ubiquitination of IL-1α is associated with increased pro-inflammatory polarization of macrophages deficient in the E3 ligase ITCH.

To evaluate risk factors associated with recurrence after radiofrequency thermocoagulation (RFT) of gasserian ganglion among patients with ophthalmic trigeminal neuralgia (TN) and prognostic factors in terms of recurrence-free survival (RFS) during a long-term follow-up.

Chronic postsurgical pain (CPSP) can be caused byperipheral nerve injury (PNI) resulting from surgical procedures and has a significant neuropathic component. This prospective, single-arm study was conducted to document the effectiveness of 10 kilohertz spinal cord stimulation (10 kHz SCS) as a treatment for patients with CPSP.