A Comparison of Patient Characteristics and Outcomes Between Patients Receiving Flexor Digitorum Superficialis Slip Excision or Isolated A1 Pulley Release for Trigger Finger.

PURPOSE: Resection of the radial or ulnar slip of the flexor digitorum superficialis (FDS) tendon is a known treatment option for persistent trigger finger. Risk factors for undergoing FDS slip excision are unclear. We hypothesized that patients who underwent A1 pulley release with FDS slip excision secondary to persistent triggering would have a higher comorbidity burden compared to those receiving A1 pulley release alone. METHODS: We identified all adult patients who underwent A1 pulley release with FDS slip excision because of persistent triggering either intraoperatively or postoperatively from 2018 to 2023. We selected a 3:1 age- and sex-matched control group who underwent isolated A1 pulley release. Charts were retrospectively reviewed for demographics, selected comorbidities, trigger finger history, and postoperative course. We performed multivariable logistic regression to assess the probability of FDS slip excision after adjusting for several variables that were significant in bivariate comparisons. RESULTS: We identified 48 patients who underwent A1 pulley release with FDS slip excision and 144 controls. Our multivariable model showed that patients with additional trigger fingers and a preoperative proximal interphalangeal (PIP) joint contracture were significantly more likely to undergo FDS slip excision. CONCLUSIONS: Patients who underwent A1 pulley release with FDS slip excision were significantly more likely to have multiple trigger fingers or a preoperative PIP joint contracture. Clinicians should counsel patients with these risk factors regarding the potential for FDS slip excision in addition to A1 pulley release to alleviate triggering of the affected digit. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Stimulating Type 1 Angiotensin Receptors on T Lymphocytes Attenuates Renal Fibrosis.

Most forms of chronic kidney disease culminate in renal fibrosis that heralds organ failure. In contrast to the protective effects of globally blocking type 1 angiotensin (AT1) receptors throughout the body, activating AT1 receptors directly on immune cells may serve protective functions. However, the effects of stimulating the T-cell AT1 receptor on the progression of renal fibrosis remain unknown. In this study, mice with T-cell-specific deletion of the dominant murine AT1 receptor isoform Lck-Cre Agtraflox/flox [total knockout (TKO)] and wild-type (WT) controls were subjected to the unilateral ureteral obstruction model of kidney fibrosis. Compared with WT controls, obstructed kidneys from TKO mice at day 14 had increased collagen 1 deposition. CD4+ T cells, CD11b+Ly6Chi myeloid cells, and mRNA levels of Th1 inflammatory cytokines are elevated in obstructed TKO kidneys, suggesting that augmented Th1 responses in the TKO mice may exaggerate renal fibrosis by driving proinflammatory macrophage differentiation. In turn, T-bet deficient (T-bet knockout) mice lacking Th1 responses have attenuated collagen deposition after unilateral ureteral obstruction. We conclude that activating the AT1 receptor on T cells mitigates renal fibrogenesis by inhibiting Th1 differentiation and renal accumulation of profibrotic macrophages.

C-C Motif Chemokine 5 Attenuates Angiotensin II-Dependent Kidney Injury by Limiting Renal Macrophage Infiltration.

Inappropriate activation of the renin angiotensin system (RAS) is a key contributor to the pathogenesis of essential hypertension. During RAS activation, infiltration of immune cells into the kidney exacerbates hypertension and renal injury. However, the mechanisms underpinning the accumulation of mononuclear cells in the kidney after RAS stimulation remain unclear. C-C motif chemokine 5 (CCL5) drives recruitment of macrophages and T lymphocytes into injured tissues, and we have found that RAS activation induces CCL5 expression in the kidney during the pathogenesis of hypertension and renal fibrosis. We therefore evaluated the contribution of CCL5 to renal damage and fibrosis in hypertensive and normotensive models of RAS stimulation. Surprisingly, during angiotensin II-induced hypertension, CCL5-deficient (knockout, KO) mice exhibited markedly augmented kidney damage, macrophage infiltration, and expression of proinflammatory macrophage cytokines compared with wild-type controls. When subjected to the normotensive unilateral ureteral obstruction model of endogenous RAS activation, CCL5 KO mice similarly developed more severe renal fibrosis and greater accumulation of macrophages in the kidney, congruent with enhanced renal expression of the macrophage chemokine CCL2. In turn, pharmacologic inhibition of CCL2 abrogated the differences between CCL5 KO and wild-type mice in kidney fibrosis and macrophage infiltration after unilateral ureteral obstruction. These data indicate that CCL5 paradoxically limits macrophage accumulation in the injured kidney during RAS activation by constraining the proinflammatory actions of CCL2.

Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI.

Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-α is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-α is suppressed or enhanced by AT1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-α levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-α production induced by cisplatin. Finally, disrupting TNF-α production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-α levels induced by cisplatin. These results illustrate discrepant tissue-specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.

Targeting cytokine signaling in salt-sensitive hypertension.

Activated immune cell populations contribute to hypertension in part through inciting damage to the kidney and by provoking inappropriate sodium reabsorption in the nephron. Inflammatory mediators called cytokines produced by T lymphocytes and macrophages act on specific sodium transporters in the kidney, augmenting their activity or expression, with consequent expansion of intravascular fluid volume and cardiac output. The overlapping functions of these cytokines, each of which may activate multiple receptors, present challenges in precisely targeting inflammatory signaling cascades in hypertension. Moreover, broad immune suppression could expose the hypertensive patient to disproportional risks of infection or malignancy. Nevertheless, the possibility that incisive immunomodulatory therapies could provide cardiovascular and renal protection through both blood pressure-dependent and -independent mechanisms justifies comprehensive investigation into the relevant signaling pathways and tissue sites in which inflammatory cytokines function to exaggerate blood pressure elevation and target organ damage in hypertension.

Intramedullary Threaded Nail Fixation of Distal Ulnar Fractures: The Surgical Technique and Case Series.

BACKGROUND:  To describe the surgical technique of non-compressive intramedullary threaded nail (IMTN) fixation of distal ulnar neck fractures and present the clinical and radiographic outcomes of four patients treated with this novel technique. METHODS: At a single Level 1 Trauma Center, a retrospective review was conducted for patients with distal ulnar neck fractures treated with retrograde IMTN between 2022 and 2024. Exclusion criteria included inadequate follow-up. A single surgeon performed all procedures using percutaneous retrograde IMTN fixation through the central disc of the triangular fibrocartilage complex (TFCC). Patients initiated a range of motion (ROM) protocol two weeks post-operatively. Post-operative radiographic images were used to calculate the ratio of IMTN diameter to the distal ulnar medullary isthmus diameter proximal to the fracture site. Radiographic changes in displacement, angulation, and ulnar variance were calculated between the first and last follow-up radiographs. Functional outcomes including grip strength and ROM were collected. RESULTS: Four patients with distal ulnar neck fractures were treated with retrograde IMTN between 2022 and 2024. They were followed for a minimum of three months post-operatively. All were female with an average age of 65 years. All distal ulna fractures were associated with operatively treated intraarticular distal radius fractures. All patients were treated with 75 mm length and 4.5 mm diameter IMTNs. IMTN-to-Isthmus ratio was greater than 60% in all cases. Average radiographic displacement and angulation were unchanged at the final follow-up. The average ulnar variance increased by 1.2 mm. At the final follow-up, there were no post-operative complications. No cases demonstrated ulnar-sided wrist pain, nonunion, or required revision surgery. CONCLUSIONS: Retrograde IMTN fixation is a novel surgical technique for the treatment of distal ulnar neck fractures. We found limited but promising post-operative radiographic and functional outcomes in our patients without reported ulnar-sided wrist pain, nonunion, or need for hardware removal.

Outcomes Following Surgical Fixation of Distal Radius Fractures in Patients With Chronic Kidney Disease.

Purpose: Moderate-to-severe chronic kidney disease (CKD, stages III-IV) and end-stage renal disease (ESRD or CKD stage V) are known to be independent risk factors for fragility fracture. Altered bone and mineral metabolism contributes to greater complications and mortality rates in the setting of fractures, although most existing literature is limited to hip fractures. We hypothesized that patients with moderate-to-severe CKD or ESRD would have greater complication rates after surgical treatment of distal radius fractures compared with those without CKD. Methods: We retrospectively identified all patients at a level 1 trauma center between 2008 and 2018 who had a diagnosis of stage III-IV CKD or ESRD at the time of operative fixation of a distal radius fracture. We recorded demographic data, comorbidities, and surgical complications. Data for readmissions within 90 days and 1-year mortality were collected. A 2:1 sex-matched control group without CKD who underwent distal radius fixation was selected for comparison, with age-adjusted analysis. Results: A total of 32 patients with CKD (78.1% CKD stage III/IV, 21.9% ESRD) and 62 without CKD were identified. The mean age was 67 ± 12 years in the CKD group and 55 ± 15 years in the control group. The CKD group had a higher Charlson Comorbidity Index (5.7 vs 2.0). Surgical complication rate in the CKD group was 12.5% (12.0% CKD III/IV; 14.3% ESRD). Neither early nor late surgical complication rates were statistically different from those in patients without CKD. Reoperation rate as well as 30- and 90-day readmission rates were similar between groups. Overall, 1-year mortality was greater in the CKD group (9.4% vs 0%). Conclusions: Surgical complications and readmission rates are similar in patients with and without CKD after distal radius fracture fixation. However, 1-year mortality rate is significantly higher after distal radius fixation in patients with moderate-to-severe CKD or ESRD. Type of study/level of evidence: Prognostic IIIa.

Outcomes Following Surgical Fixation of Upper Extremity Fractures in Patients with Chronic Kidney Disease.

Purpose: Moderate to severe (stage III-IV) chronic kidney disease (CKD) and end stage renal disease (ESRD) have been shown to be independent risk factors for sustaining a fragility fracture. High rates of complications and mortality are associated with fracture fixation in patients with CKD, but existing literature is limited. It is unknown how CKD stage III-IV or ESRD affects outcomes in upper-extremity fractures. We hypothesize that patients with CKD stage III-IV or ESRD will have high complication rates after surgical fixation of upper extremity fractures. Methods: We identified all patients between 2008 and 2018 who underwent operative fixation of an upper extremity fracture proximal to the distal radius with a diagnosis of CKD stage III-IV or ESRD at the time of injury. Those with an acute kidney injury at the time of injury or a history of a kidney transplant were excluded. Demographics, medical complications, and surgical complications were collected retrospectively. Data on readmissions within 90 days and mortality within 1 year were also collected. Results: Thirty-five patients were identified. Three patients had ESRD. Fractures included two clavicle, twelve proximal humerus, one humeral shaft, ten distal humerus, five olecranon, two ulnar shaft, one radial shaft, and two both-bone forearm fractures. In total, 91.4% of fractures were closed injuries. Surgical complications occurred in 40% of patients. The reoperation rate was 11.4%, and all cases of reoperation involved hardware removal. The all-cause 90-day readmission rate was 34.3%. The 1-year mortality rate was 8.6%. Conclusions: Surgical complications occurred in 40% of patients with CKD stage III-IV or ESRD who underwent fixation for an upper extremity fracture. It is important to counsel these patients regarding their high risk for complications. Further research is needed to investigate and identify how to mitigate risk. Type of study/level of evidence: Prognostic IV.

Characterization of Lumbar Lordosis: Influence of Age, Sex, Vertebral Body Wedging, and L4-S1.

STUDY DESIGN: Retrospective radiographic review. OBJECTIVE: The objectives of the study were to determine the contributions to lumbar lordosis (LL) through both the vertebrae and the intervertebral disc (IVD), and to investigate the relationships between lumbar sagittal spine measurements and age and gender. SUMMARY OF BACKGROUND DATA: A small body of literature exists on the relative contributions of vertebral body and IVD morphology to LL, the effects of L4-S1 on overall LL, and the relationships/correlations between lumbar sagittal spine measurements. METHODS: Patients who met the inclusion criteria were retrospectively evaluated. Measurements included LL, pelvic incidence (PI), and % contributions of vertebral body wedging/IVD wedging/L4-S1 to LL. Patients were separated into groups by age and sex, demographic data were collected, and statistical analysis was completed. RESULTS: LL decreased with age, although PI remained similar. Females demonstrated increased LL and vertebral body wedging % than males. Males demonstrated increased L4-S1% than females. Despite a decrease in LL with age, patients maintained L4-S1% and IVD wedging %. There was a significant negative relationship between PI and IVD wedging, PI and L4-S1%, and LL and L4-S1%. CONCLUSIONS: During aging, the lumbar spine loses LL linearly. This occurs in the IVD and vertebral bodies. Females have increased LL compared with males, because of an increase in vertebral body wedging and IVD/vertebral wedging cranial to L4. In patients with high PI or LL, increased LL occurs from cranial to L4 and from vertebral body wedging.

The role of leukotriene inhibition using a 5-lipoxygenase (5-LO) inhibitor in a joint contracture model.

PURPOSE: Arthrofibrosis is a common inflammatory complication of joint trauma and surgery. 5lipoxygenase (5-LO) is a key enzyme involved in inflammation. Inhibition of 5-LO has been shown to reduce inflammation in heart and lung models but has not been examined in a joint contracture model. METHODS: Twenty-six rats underwent joint contracture. Six rats served as non-surgical controls. A 5-LO inhibitor, caffeic acid (CA), suspended in 10% ethanol was orally administered to 14 rats and ethanol without CA to the remaining 12 rats daily for 21 days. Leukotriene B4 (LTB4) levels were measured, both systemically and locally. 5-LO levels in the posterior capsule were quantified by measuring the ratio of the length of the posterior capsule demonstrating 5-LO immunostaining to the total length of the capsule. RESULTS: Joint contracture was successfully achieved in all rats who underwent manipulation. Levels of 5- LO measured in the posterior capsule were significantly increased in the animals who underwent surgery (56%/44-64) compared to the non-surgical control animals (7%/4-9). LTB4 levels were found to be significantly lower in the non-surgical control animals (107.79 ± 34.08 pg/ml) compared to all surgical animals (157.6 ± 55.3 pg/ml). CONCLUSION: Surgical intervention resulted in increased 5-LO activity of the synovial surface of the posterior capsule and increased LTB4 levels in the patellar tendon-fat pad. Oral administration of the 5LO inhibitor, CA, was ineffective at reducing systemic and local LTB4 levels and preventing knee joint contracture. Inhibiting 5-LO activity may still be effective in preventing arthrofibrosis and warrants further investigation.

2-Octyl Cyanoacrylate (Dermabond®) Inhibits Bridging Bone Formation of Articular Fractures in a Rat Model.

One technique often used for small intraarticular fracture fixation involves the use of 2-octyl-cyanoacrylate (2-OCTA) (Dermabond®, Ethicon, Inc., Raritan, USA). The purpose of this study was to determine if 2-OCTA impedes bony healing. Osteochondral plugs in 38 retired Sprague-Dawley rats were created in both hind legs. Each rat had one plug dipped in 2-OCTA before fixation and one control plug. H&E staining was used to quantify bone bridging. The 2-OCTA group had a mean bridging bone circumference of 22.80%, significantly less than 67.75% in the control group (p<0.05). Our data suggests that 2-OCTA blocks bridging bone formation, making it a poor choice for fracture fixation.

Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron.

Hypertension is among the most prevalent and catastrophic chronic diseases worldwide. While the efficacy of renin angiotensin system (RAS) blockade in lowering blood pressure illustrates that the RAS is broadly activated in human hypertension, the frequent failure of RAS inhibition to prevent or reverse hypertensive organ damage highlights the need for novel therapies to combat RAS-dependent hypertension. We previously discovered elevated levels of the macrophage cytokine IL-1 in the kidney in a murine model of RAS-mediated hypertension. Here we report that IL-1 receptor (IL-1R1) deficiency or blockade limits blood pressure elevation in this model by mitigating sodium reabsorption via the NKCC2 co-transporter in the nephron. In this setting, IL-1R1 activation prevents intra-renal myeloid cells from maturing into Ly6C(+)Ly6G(-) macrophages that elaborate nitric oxide, a natriuretic hormone that suppresses NKCC2 activity. By revealing how the innate immune system regulates tubular sodium transport, these experiments should lead to new immunomodulatory anti-hypertensive therapies.