Arthroplasty for femoral neck fractures is at risk for under restoration of lateral femoral offset.

PURPOSE: The aim of the study was to determine the restoration of hip biomechanics through lateral offset, leg length, and acetabular component position when comparing non-arthroplasty surgeons (NAS) to elective arthroplasty surgeons (EAS). METHODS: 131 patients, with a femoral neck fracture treated with a THA by 7 EAS and 20 NAS, were retrospectively reviewed. 2 blinded observers measured leg-length discrepancy, femoral offset, and acetabular component position. Multivariate logistic regression models examined the association between the surgeon groups and restoration of lateral femoral, acetabular offset, leg length discrepancy, acetabular anteversion, acetabular position, and component size, while adjusting for surgical approach and spinal pathology. RESULTS: NAS under-restored 4.8 mm of lateral femoral offset (43.9 ± 8.7 mm) after THA when compared to the uninjured side (48.7 ± 7.1 mm, p = 0.044). NAS were at risk for under-restoring lateral femoral offset when compared to EAS (p = 0.040). There was no association between lateral acetabular offset, leg length, acetabular position, or component size and surgeon type. CONCLUSIONS: Lateral femoral offset is at risk for under-restoration after THA for femoral neck fractures, when performed by surgeons that do not regularly perform elective THA. This indicates that lateral femoral offset is an under-appreciated contributor to hip instability when performing THA for a femoral neck fracture. Lateral femoral offset deserves as much attention and awareness as acetabular component position since a secondary analysis of our data reveal that preoperative templating and intraoperative imaging did not prevent under-restoration.

Lack of alignment between orthopaedic surgeon priorities and patient expectations in total joint arthroplasty.

BACKGROUND: Healthcare systems are shifting toward "patient-centered" care often without assessing the values important to patients. Analogously, the interests of the patient may be disparate with physician interests, as pay-for-performance models become common. The purpose of the study was to determine which medical preferences are essential for patients during their surgical care. METHODS: This prospective, observational study surveyed 102 patients who had undergone a primary knee replacement and/or hip replacement surgery about hypothetical scenarios regarding their surgical experience. Data analysis included categorical variables presented as a number and percent, while continuous variables presented as mean and standard deviation. Statistical analysis for anticoagulation data included the Pearson chi-square test and one-way ANOVA test. RESULTS: A large majority, 73 patients (72%), would not pay to have a four-centimeter or smaller incision. The remaining 29 patients (28%) would prefer to have a four-centimeter or smaller incision and would pay a mean of $1,328 ± 1,629 for that day. A significant number of patients preferred not to use anticoagulation (p = 0.019); however, the value attributed to avoiding a specific method of anticoagulation was found not to be significant (p = 0.507). CONCLUSIONS: The study determined the metrics prioritized by hospitals and surgeons are not important to the majority of patients when they evaluate their own care. These disconnects in the entitlements patients expect and receive can be solved by including patients in discussions with physicians and hospital systems.

An Inexpensive 3D Printed Mouse Model of Successful, Complication-free Long Bone Distraction Osteogenesis.

Distraction osteogenesis (DO) is used for skeletal defects; however, up to 50% of cases exhibit complications. Previous mouse models of long bone DO have been anecdotally hampered by postoperative complications, expense, and availability. To improve clinical techniques, cost-effective, reliable animal models are needed. Our focus was to develop a new mouse tibial distractor, hypothesized to result in successful, complication-free DO. Methods: A lightweight tibial distractor was developed using CAD and 3D printing. The device was fixed to the tibia of C57Bl/6J mice prior to osteotomy. Postoperatively, mice underwent 5 days latency, 10 days distraction (0.15 mm every 12 hours), and 28 days consolidation. Bone regeneration was examined on postoperative day 43 using micro-computed tomography (µCT) and Movat's modified pentachrome staining on histology (mineralized volume fraction and pixels, respectively). Costs were recorded. We compared cohorts of 11 mice undergoing sham, DO, or acute lengthening (distractor acutely lengthened 3.0 mm). Results: The histological bone regenerate was significantly increased in DO (1,879,257 ± 155,415 pixels) compared to acute lengthening (32847 ± 1589 pixels) (P < 0.0001). The mineralized volume fraction (bone/total tissue volume) of the regenerate was significantly increased in DO (0.9 ± 0.1) compared to acute lengthening (0.7 ± 0.1) (P < 0.001). There was no significant difference in bone regenerate between DO and sham. The distractor was relatively low cost ($11), with no complications. Conclusions: Histology and µCT analysis confirmed that the proposed tibial DO model resulted in successful bone formation. Our model is cost-effective and reproducible, enabling implementation in genetically dissectible transgenic mice.

When intravenous vancomycin prophylaxis is needed in shoulder arthroplasty, incomplete administration is associated with increased infectious complications.

BACKGROUND: Vancomycin is often used as antimicrobial prophylaxis for shoulder arthroplasty (SA) either when first generation cephalosporins are contraindicated or colonization with resistant bacteria is anticipated. In general, vancomycin necessitates longer infusion times to mitigate potential side effects. When infusion is started too close to the time of the incision, administration may not be complete during surgery. This study evaluated whether incomplete administration of intravenous vancomycin prior to SA affects the rate of infectious complications. METHODS: Between 2000 and 2019, all primary SA types (hemiarthroplasty, anatomic total SA, reverse SA) performed at a single institution for elective and trauma indications using intravenous vancomycin as the primary antibiotic prophylaxis and a minimum follow-up of 2 yr were identified. The time between the initiation of vancomycin and skin incision was calculated. Complete administration was defined as at least 30 min of infusion prior to incision. Demographic characteristics and infectious complications including survival free of prosthetic joint infection (PJI) were generated. Multivariable analyses were conducted to evaluate the association between vancomycin timing and the development of PJI. RESULTS: A total of 461 primary SAs were included. Infusion was incomplete (< 30 minutes preoperatively) for 163 [35.4%] SA and complete (> 30 minutes preoperatively) for 298 [64.6%] SAs. The incomplete group demonstrated higher rates of any infectious complication (8% vs. 2.3%; P = .005), PJI (5.5% vs. 1%; P = .004), and reoperation inclusive of revision due to infectious complications (4.9% vs. 1%; P = .009). Survivorship free of PJI was worse in SA with incomplete compared to those with complete vancomycin administration. Survival rates for incomplete and complete administration were 97.6% and 99.3% at 1 mo, 95.7% and 99.0% at 2 yr, 95.1% and 99.0% at 5 yr, and 93.9% and 99.0% at 20 yr, respectively (P = .006). Multivariable analyses confirmed that incomplete vancomycin administration was an independent risk factor for PJI compared with complete administration (hazard ratio, 4.22 [95% confidence interval, 1.12-15.90]; P = .033), even when other independent predictors of PJI (age, male sex, prior surgery, methicillin-resistant Staphylococcus aureus colonization, and follow-up) were considered. CONCLUSIONS: When vancomycin is the primary prophylactic agent used at the time of primary SA, incomplete administration (infusion to incision time under 30 min) seems to adversely increase the rates of infectious complications and PJI. Prophylaxis protocols should ensure that complete vancomycin administration is achieved to minimize infection after SA.

Skin Grafting, Cryopreservation, and Diseases: A Review Article.

Food supplements may be consumed through diet and have been shown to modify skin functions, making them helpful in the management of skin aging. However, there are not many clinical trials that back up these assertions. The stratum corneum, which acts as the organism's contact with its environment, is the principal function of the epidermis of land vertebrates. Antioxidants are chemicals that slow down or prevent other molecules from oxidizing. In people's diets, their use has considerably expanded in recent years. Due to their benefits for health, nutrition, and therapy, natural antioxidants are increasingly being used in place of synthetic antioxidant components. A popular component thought to be an antioxidant is hydrolyzed collagen. With aging comes a steady loss of physiological integrity, capacity to handle stress from the inside out, and function. This is a byproduct of several intricate biological processes that are affected by diseases both local and systemic as well as constitutive and environmental variables. Systemic and constitutive (genetic) variables influence skin aging and its phenotypic manifestation. The biological process of skin aging is complicated and impacted by both external and endogenous causes. The primary contributor to skin cancer is sun exposure. Ultraviolet radiation from the sun can kill skin cells by directly absorbing DNA damage. The skin's hydration is a crucial factor that affects its mechanical and physical characteristics. This study looks at how the stratum corneum's molecular and macroscopic characteristics interact and change with skin wetness. Although there is little information written about them and even less is understood about them, moisturizers are a crucial component of a dermatologist's toolkit. There is a plethora of anticipated skin products on the market, but their true scientific function is yet unknown. These items play a well-known part in many skin problems, while occasionally being dismissed as simple cosmetics.

Craniofacial and Long Bone Development in the Context of Distraction Osteogenesis.

BACKGROUND: Bone retains regenerative potential into adulthood, and surgeons harness this plasticity during distraction osteogenesis. The underlying biology governing bone development, repair, and regeneration is divergent between the craniofacial and appendicular skeleton. Each type of bone formation is characterized by unique molecular signaling and cellular behavior. Recent discoveries have elucidated the cellular and genetic processes underlying skeletal development and regeneration, providing an opportunity to couple biological and clinical knowledge to improve patient care. METHODS: A comprehensive literature review of basic and clinical literature regarding craniofacial and long bone development, regeneration, and distraction osteogenesis was performed. RESULTS: The current understanding in craniofacial and long bone development and regeneration is discussed, and clinical considerations for the respective distraction osteogenesis procedures are presented. CONCLUSIONS: Distraction osteogenesis is a powerful tool to regenerate bone and thus address a number of craniofacial and appendicular skeletal deficiencies. The molecular mechanisms underlying bone regeneration, however, remain elusive. Recent work has determined that embryologic morphogen gradients constitute important signals during regeneration. In addition, striking discoveries have illuminated the cellular processes underlying mandibular regeneration during distraction osteogenesis, showing that skeletal stem cells reactivate embryologic neural crest transcriptomic processes to carry out bone formation during regeneration. Furthermore, innovative adjuvant therapies to complement distraction osteogenesis use biological processes active in embryogenesis and regeneration. Additional research is needed to further characterize the underlying cellular mechanisms responsible for improved bone formation through adjuvant therapies and the role skeletal stem cells play during regeneration.

A Small Amount of Retraction Force Results in Inadvertent Piriformis Muscle Damage During a Piriformis-Sparing Approach to the Hip.

BACKGROUND: Piriformis-sparing approaches to the hip allow surgeons to avoid releasing the piriformis tendon during total hip arthroplasty; however, the consequences of retracting an intact piriformis tendon during such an approach remain ill-defined. The present study aimed to determine the upper limit of force that can be applied during retraction of the piriformis tendon to expose the hip, and to quantify the resultant damage to the piriformis musculotendinous complex. METHODS: A patent-pending instrumented retractor was designed to record the applied force, duration, and angle of retraction during a piriformis-sparing posterior approach to the hip. In addition to the data collected with use of the instrumented retractor, damage to the piriformis muscle and tendon was quantified by a blinded observer. RESULTS: There was no damage to the piriformis tendon in 22 (96%) of 23 hips during piriformis retraction for visualization of the hip capsule; however, there was complete or partial damage to the piriformis muscle at the sacral origin, belly, or musculotendinous junction (i.e., outside the surgical field) noted in 21 (91%) of 23 hips. The mean peak force to failure of the piriformis muscle was exceedingly small (29.0 ± 9.4 N; range, 10.1 to 44.9 N). CONCLUSIONS: The mean peak force applied to the piriformis retractor is much less than the force required for several common daily activities, such as opening a door or crushing an empty aluminum can. Soft-tissue damage that occurs outside the surgical field during the retraction of unreleased muscles, like the piriformis muscle, is common and remains an uncontrolled surgical variable. This inadvertent soft-tissue damage is not routinely accounted for when accessing the invasiveness of a procedure. Hence, it is no longer adequate to define a minimally invasive surgical procedure simply as an approach that involves the limited release of anatomical structures. CLINICAL RELEVANCE: The use of instrumented retractors may redefine surgical invasiveness by providing data that could alter our understanding of the soft-tissue damage caused by retraction and open the possibility of robot-assisted or damage-limiting retractor systems.

Mechanisms of bone development and repair.

Bone development occurs through a series of synchronous events that result in the formation of the body scaffold. The repair potential of bone and its surrounding microenvironment - including inflammatory, endothelial and Schwann cells - persists throughout adulthood, enabling restoration of tissue to its homeostatic functional state. The isolation of a single skeletal stem cell population through cell surface markers and the development of single-cell technologies are enabling precise elucidation of cellular activity and fate during bone repair by providing key insights into the mechanisms that maintain and regenerate bone during homeostasis and repair. Increased understanding of bone development, as well as normal and aberrant bone repair, has important therapeutic implications for the treatment of bone disease and ageing-related degeneration.

Mechanical compression augments venous flow equal to intermittent pneumatic compression.

Intermittent pneumatic compression is part of the current standard of care model for preventing venous thromboembolic events (VTE) after total joint arthroplasty. Pneumatic motors limit the rate of inflation resulting in bulky devices with uncomfortable sleeves that inhibited patient compliance and mobility. Nonpneumatic mechanical devices are an alternative for providing mobile, graded, intermittent, sequential, rapid, and monitorable compression posthospitalization. Fifteen healthy volunteers underwent mechanical compression using the Cirvo (Radial Medical, Mountain View, CA) as well as pneumatic compression with four commercially available systems (VenaFlow Elite, Kendall SCD Compression System, ActiveCare DVT, Vasculaire Compression System) and manual calf compression. Peak flow velocity (PFV) was measured by ultrasound of the femoral vein during compression and at baseline. Mechanical compression for 1 second resulted in a significant increase in femoral venous PFV to 107.8 ± 38.2 cm/s from 17.1 ± 4.7 cm/s at baseline (P < .001). The change in femoral venous PFV with mechanical compression for 1 second (90.7 ± 34.9 cm/s) was not statistically different from pneumatic compression from VenaFlow system (106.0 ± 35.6 cm/s, P = .124) and statistically lower than manual calf compression (115.5 ± 26.8 cm/s, P = .015). Pneumatic compression from the VenaFlow system produced the largest change in femoral venous PFV of all commercial pneumatic systems tested. Mechanical compression replicates or exceeds femoral venous PFV available from currently available intermittent pneumatic compression.

Skeletal Stem Cell-Schwann Cell Circuitry in Mandibular Repair.

Regenerative paradigms exhibit nerve dependency, including regeneration of the mouse digit tip and salamander limb. Denervation impairs regeneration and produces morphological aberrancy in these contexts, but the direct effect of innervation on the stem and progenitor cells enacting these processes is unknown. We devised a model to examine nerve dependency of the mouse skeletal stem cell (mSSC), the progenitor responsible for skeletal development and repair. We show that after inferior alveolar denervation, mandibular bone repair is compromised because of functional defects in mSSCs. We present mSSC reliance on paracrine factors secreted by Schwann cells as the underlying mechanism, with partial rescue of the denervated phenotype by Schwann cell transplantation and by Schwann-derived growth factors. This work sheds light on the nerve dependency of mSSCs and has implications for clinical treatment of mandibular defects.

Failed Progenitor Specification Underlies the Cardiopharyngeal Phenotypes in a Zebrafish Model of 22q11.2 Deletion Syndrome.

Microdeletions involving TBX1 result in variable congenital malformations known collectively as 22q11.2 deletion syndrome (22q11.2DS). Tbx1-deficient mice and zebrafish recapitulate several disease phenotypes, including pharyngeal arch artery (PAA), head muscle (HM), and cardiac outflow tract (OFT) deficiencies. In zebrafish, these structures arise from nkx2.5+ progenitors in pharyngeal arches 2-6. Because pharyngeal arch morphogenesis is compromised in Tbx1-deficient animals, the malformations were considered secondary. Here, we report that the PAA, HM, and OFT phenotypes in tbx1 mutant zebrafish are primary and arise prior to pharyngeal arch morphogenesis from failed specification of the nkx2.5+ pharyngeal lineage. Through in situ analysis and lineage tracing, we reveal that nkx2.5 and tbx1 are co-expressed in this progenitor population. Furthermore, we present evidence suggesting that gdf3-ALK4 signaling is a downstream mediator of nkx2.5+ pharyngeal lineage specification. Collectively, these studies support a cellular mechanism potentially underlying the cardiovascular and craniofacial defects observed in the 22q11.2DS population.

Adjuvant systemic therapy after resection of node positive gallbladder cancer: Time for a well-designed trial? (Results of a US-national retrospective cohort study).

BACKGROUND: Ideal oncologic management of gallbladder carcinoma (GBCA) after complete surgical resection is unclear. We sought to define benefit of post-resection adjuvant systemic chemotherapy alone in T2 or greater gallbladder carcinoma utilising a large national dataset. STUDY DESIGN: The National Cancer Data Base (NCDB) 2004-2012 cohort was retrospectively reviewed for patients with GBCA (T2+) undergoing curative-intent resection and surviving at least 6 weeks. Univariate group comparisons, unadjusted Kaplan-Meier and adjusted Cox proportional hazards analyzed overall survival. RESULTS: 4373 patients were included (N = 2479 T2, N = 1894 T3/4). Overall, 22.1% of patients received adjuvant chemotherapy. Use of multi-agent chemotherapy increased during the study period. Patients receiving adjuvant therapy were younger, had fewer comorbidities, more often node-positive and more likely R1-margins than those receiving surgery alone. Unadjusted overall survival was improved in all patients with node-positive disease as well as for those with inadequate nodal staging. The benefit of chemotherapy persisted after adjustment for patient and tumor factors. CONCLUSION: Adjuvant systemic chemotherapy is associated with survival benefit in patients with T2 or greater GBCA with node positive disease. We recommend a multidisciplinary approach in these patients as less than 1-in-4 of them currently receive adjuvant chemotherapy. Future clinical trials should address adjuvant chemotherapy in node positive GBCA.

A Validated Nomogram to Predict Upstaging of Ductal Carcinoma in Situ to Invasive Disease.

BACKGROUND: Approximately 8-56% of patients with a core needle biopsy (CNB) diagnosis of ductal carcinoma in situ (DCIS) will be upstaged to invasive disease at the time of excision. Patients with invasive disease are recommended to undergo axillary nodal staging, most often requiring a second operation. We developed and validated a nomogram to preoperatively predict percentage of risk for upstaging to invasive cancer. METHODS: We reviewed 834 cases of DCIS on CNB between January 2004 and October 2014. Multivariable analysis was used to evaluate CNB and imaging factors to develop a nomogram to predict the risk of upstaging from DCIS to invasive cancer. This nomogram was validated with an external dataset of 579 similar patients between November 1998 and September 2016. An area under the receiver operating characteristic curve was constructed to evaluate nomogram discrimination. RESULTS: The rate of upstaging to invasive disease was 118/834 (14.1%). On multivariable analysis, grade on CNB and imaging factors, including mass lesion, multicentric disease, and largest linear dimension, were associated with upstage to invasive disease, and was used to develop a nomogram (c-statistic 0.71). In the external validation dataset, 62/579 (10.7%) patients were upstaged to invasive disease. Our nomogram was validated in this dataset with a c-statistic of 0.71. CONCLUSION: For patients with a CNB diagnosis of DCIS, our validated nomogram using DCIS grade on biopsy, and imaging factors of mass lesion, multicentric disease, and largest linear dimension, may be used for preoperative assessment of risk of upstaging to invasive disease, allowing patient counseling regarding axillary staging at the time of definitive surgery.

Identifying a subset of patients with DCIS who have a low likelihood of residual disease at surgical excision following a core needle biopsy.

BACKGROUND AND OBJECTIVES: Current randomized controlled trials are investigating the outcomes of non-surgical treatment for patients with ductal carcinoma in situ (DCIS). We sought to evaluate pre-operative factors associated with no residual disease at definitive resection following a core needle biopsy (CNB) diagnosis of DCIS. METHODS: Eight hundred and thirty-four operations for DCIS were performed at our institution between January 2004 and October 2014. We evaluated patient and biopsy tumor characteristics to determine pre-operative factors associated with no residual disease at surgical resection using uni- and multivariable analyses. RESULTS: Sixty-nine patients (8%) had no residual disease on final pathology. On multivariable analysis, low- or intermediate-grade lesions, <1 cm in size on mammography, and lesions where ≥90% of calcifications were removed correlated with finding no residual disease on final pathology, c-statistic 0.84. Of the 14 patients with all three low-risk factors, 36% had no residual disease on final pathology. CONCLUSIONS: Although our multivariable analysis performed well, its clinical utility would be limited as we were unable to identify a subset of patients with DCIS in whom the probability of finding no residual disease is low enough to consider routine use of non-surgical management.

Epigenetic-based combinatorial resveratrol and pterostilbene alters DNA damage response by affecting SIRT1 and DNMT enzyme expression, including SIRT1-dependent γ-H2AX and telomerase regulation in triple-negative breast cancer.

BACKGROUND: Nutrition is believed to be a primary contributor in regulating gene expression by affecting epigenetic pathways such as DNA methylation and histone modification. Resveratrol and pterostilbene are phytoalexins produced by plants as part of their defense system. These two bioactive compounds when used alone have been shown to alter genetic and epigenetic profiles of tumor cells, but the concentrations employed in various studies often far exceed physiologically achievable doses. Triple-negative breast cancer (TNBC) is an often fatal condition that may be prevented or treated through novel dietary-based approaches. METHODS: HCC1806 and MDA-MB-157 breast cancer cells were used as TNBC cell lines in this study. MCF10A cells were used as control breast epithelial cells to determine the safety of this dietary regimen. CompuSyn software was used to determine the combination index (CI) for drug combinations. RESULTS: Combinatorial resveratrol and pterostilbene administered at close to physiologically relevant doses resulted in synergistic (CI <1) growth inhibition of TNBCs. SIRT1, a type III histone deacetylase (HDAC), was down-regulated in response to this combinatorial treatment. We further explored the effects of this novel combinatorial approach on DNA damage response by monitoring γ-H2AX and telomerase expression. With combination of these two compounds there was a significant decrease in these two proteins which might further resulted in significant growth inhibition, apoptosis and cell cycle arrest in HCC1806 and MDA-MB-157 breast cancer cells, while there was no significant effect on cellular viability, colony forming potential, morphology or apoptosis in control MCF10A breast epithelial cells. SIRT1 knockdown reproduced the effects of combinatorial resveratrol and pterostilbene-induced SIRT1 down-regulation through inhibition of both telomerase activity and γ-H2AX expression in HCC1806 breast cancer cells. As a part of the repair mechanisms and role of SIRT1 in recruiting DNMTs, the effects of this combination treatment was also explored on DNA methyltransferases (DNMTs) expression. Interestingly, the compounds resulted in a significant down-regulation of DNMT enzymes with no significant effects on DNMT enzyme expression in MCF10A control cells. CONCLUSION: Collectively, these results provide new insights into the epigenetic mechanisms of a novel combinatorial nutrient control strategy that exhibits synergy and may contribute to future recalcitrant TNBC prevention and/or therapy.