Osteoarthritis (OA) is a debilitating inflammation related disease characterized by joint pain and effusion, loss of mobility, and deformity that may result in functional joint failure and significant impact on quality of life. Once thought of as a simple “wear and tear” disease, it is now widely recognized that OA has a considerable metabolic component and is related to chronic inflammation. Defects associated with primary cilia have been shown to be cause OA-like changes in Bardet–Biedl mice. We examined the role of dysfunctional primary cilia in OA in mice through the regulation of the previously identified degradative and pro-inflammatory molecular pathways common to OA. We observed an increase in the presence of pro-inflammatory markers TGFβ-1 and HTRA1 as well as cartilage destructive protease MMP-13 but a decrease in DDR-2. We observed a morphological difference in cartilage thickness in Bbs1M390R/M390R mice compared to wild type (WT). We did not observe any difference in OARSI or Mankin scores between WT and Bbs1M390R/M390R mice. Primary cilia appear to be involved in the upregulation of biomarkers, including pro-inflammatory markers common to OA.

Following traumatic peripheral nerve injury, adequate restoration of function remains an elusive clinical goal. Recent research highlights the complex role that the immune system plays in both nerve injury and regeneration. Pro-regenerative processes in wounded soft tissues appear to be significantly mediated by cytokines of the type 2 immune response, notably interleukin (IL)-4. While IL-4 signaling has been firmly established as a critical element in general tissue regeneration during wound healing, it has also emerged as a critical process in nerve injury and regeneration. In this context of peripheral nerve injury, endogenous IL-4 signaling has recently been confirmed to influence more than leukocytes, but including also neurons, axons, and Schwann cells. Given the role IL-4 plays in nerve injury and regeneration, exogenous IL-4 and/or compounds targeting this signaling pathway have shown encouraging preliminary results to treat nerve injury or other neuropathy in rodent models. In particular, the exogenous stimulation of the IL-4 signaling pathway appears to promote postinjury neuron survival, axonal regeneration, remyelination, and thereby improved functional recovery. These preclinical data strongly suggest that targeting IL-4 signaling pathways is a promising translational therapy to augment treatment approaches of traumatic nerve injury. However, a better understanding of the type 2 immune response and associated signaling networks functioning within the nerve injury microenvironment is still needed to fully develop this promising therapeutic avenue.

Purpose: We aimed to quantify the stigma associated with digital amputation using the Neuro-QOL Stigma patient-reported outcomes instrument and examine the patient and injury factors associated with a more severe amputation stigma experience. Methods: This descriptive retrospective cohort study analyzed 164 patients who underwent digital amputation. Records were reviewed for age at amputation, sex, indication, laterality, level, number of amputated digits, and a diagnosis of depression that preceded amputation. Enrolled patients remotely completed the Neuro-QOL stigma computer adaptive test, a battery of PROMIS instruments, and a questionnaire clarifying personal/injury details. Multivariable analysis was used to identity factors associated with a more severe stigma experience.Results: Among 164 digital amputees enrolled, the observed mean Neuro-QOL Stigma score of 47.2 +/- 8 is slightly below the population mean of 50. Younger age, a worker’s compensation claim, and a diagnosis of depression at the time of amputation are each independently associated with a more severe stigma experience after digital amputation. Neither socioeconomic variables, anatomic details of the injury, nor mechanism were independently associated with Neuro-QOL Stigma. Conclusions: While we have previously targeted patients with more severe injuries for discussion of coping with physical stigma, our findings suggest that attention should perhaps instead be focused on digital amputees who are young, depressed, and/or involved with worker’s compensation. A surgeon may be of service to the at-risk patient by offering referral to a mental health provider who can offer depression treatment and/or support the patient’s process of coping and adjustment.

BACKGROUND: Successful intraoperative microvascular anastomoses are essential for deep inferior epigastric perforator (DIEP) flap survival. This study identifies factors associated with anastomotic failure during DIEP flap reconstruction and analyzes the impact of these anastomotic failures on post-operative patient outcomes and surgical costs. METHODS: A retrospective cohort study was conducted of patients undergoing DIEP flap reconstruction at two high-volume tertiary care centers from January 2017 to December 2020. Patient demographics, intraoperative management, anastomotic technique, and post-operative outcomes were collected. Data were analyzed using Student’s t-tests, chi-square analysis, and multivariate logistic regression. RESULTS: Of the 270 patients included in our study (mean age 52, majority Caucasian [74.5%]), intraoperative anastomotic failure occurred in 26 (9.6%) patients. Increased number of circulating nurses increased risk of anastomotic failure (Odds Ratio (OR) 1.02, 95% Confidence Interval (CI) 1.00-1.03, P<0.05). Presence of a junior resident also increased risk of anastomotic failure (OR 2.42, 95% CI 1.01-6.34, P<0.05). Increased surgeon years in practice was associated with decreased failures (OR 0.12, CI 0.02-0.60, P<0.05). Intraoperative anastomotic failure increased the odds of post-operative hematoma (OR 8.85, CI 1.35-59.1, P<0.05) and was associated with longer operating room times (bilateral DIEP: 2.25 hours longer, P<0.05), longer hospital stays (2.2 days longer, P<0.05), and higher total operating room cost ($28,529.50 versus $37,272.80, P<0.05). CONCLUSION: Intraoperative anastomotic failures during DIEP flap reconstruction are associated with longer, more expensive cases and increased rates of post-operative complications. Presence of increased numbers of circulators and junior residents was associated with increased risk of anastomotic failure. Future research is necessary to develop practice guidelines for optimizing patient and surgical factors for intraoperative anastomotic success.

Background: Diabetes is a well-established risk factor for severe digital infection, and patients are more likely to require digital amputation for adequate source control. This study aims to identify factors predictive of digital amputation compared with preservation in patients with diabetes who present with surgically treated finger infections. Methods: Current Procedural Terminology (CPT) and International Classification of Diseases Versions 9 and 10 (ICD-9/10) databases from a single academic medical center were queried to identify patients with type 1 or type 2 diabetes mellitus who underwent surgical treatment in the operating room for treatment of a digital infection from 2010 to 2020. Electronic medical records were reviewed to obtain historical and acute clinical variables at the time of hospital presentation. Bivariate and multivariable regression were used to identify factors associated with amputation. Results: In total, 145 patients (61 digital amputation, 84 digital preservation) met inclusion criteria for this retrospective cohort study. Mean hospital stay was 6 days, and the average patient underwent 2 operations. Multivariable analysis revealed that the presence of osteomyelitis, ipsilateral upper extremity dialysis fistula, end-stage renal disease, and vascular disease each had significant independent predictive value for amputation rather than digital preservation. Conclusions: Digital amputation is common in the setting of diabetic finger infection. The 4 variables found to independently predict the outcome of amputation can be understood as factors which decrease the likelihood of successful digital salvage and increase the potential consequence of ongoing uncontrolled infection. Further study should focus on clinical factors affecting surgical decision making and how the treatment rendered affects patient outcomes.