Deciding without data: clinical decision-making in pediatric orthopedic surgery.

OBJECTIVE: Identifying when and how often decisions are made based on high-quality evidence can inform the development of evidence-based treatment plans and care pathways, which have been shown to improve quality of care and patient safety. Evidence to guide decision-making, national guidelines and clinical pathways for many conditions in pediatric orthopedic surgery are limited. This study investigated decision-making rationale and quantified the evidence supporting decisions made by pediatric orthopedic surgeons in an outpatient clinic. DESIGN/SETTING/PARTICIPANTS/INTERVENTION(S)/MAIN OUTCOME MEASURE(S): We recorded decisions made by eight pediatric orthopedic surgeons in an outpatient clinic and the surgeon's reported rationale behind the decisions. Surgeons categorized the rationale for each decision as one or a combination of 12 possibilities (e.g. 'Experience/anecdote,' 'First principles,' 'Trained to do it,' 'Arbitrary/instinct,' 'General study,' 'Specific study'). RESULTS: Out of 1150 total decisions, the most frequent decisions were follow-up scheduling, followed by bracing prescription/removal. The most common decision rationales were 'First principles' (n = 310, 27.0%) and 'Experience/anecdote' (n = 253, 22.0%). Only 17.8% of decisions were attributed to scientific studies, with 7.3% based on studies specific to the decision. As high as 34.6% of surgical intervention decisions were based on scientific studies, while only 10.4% of follow-up scheduling decisions were made with studies in mind. Decision category was significantly associated with a basis in scientific studies: surgical intervention and medication prescription decisions were more likely to be based on scientific studies than all other decisions. CONCLUSIONS: With increasing emphasis on high value, evidence-based care, understanding the rationale behind physician decision-making can educate physicians, identify common decisions without supporting evidence and help create clinical care pathways in pediatric orthopedic surgery. Decisions based on evidence or consensus between surgeons can inform pathways and national guidelines that minimize unwarranted variation in care and waste. Decision support tools and aids could also be implemented to guide these decisions.

A Human-Derived, Collagen-Rich Hydrogel Augments Wound Healing in a Diabetic Animal Model.

BACKGROUND: Application of collagen products to wounds has been shown to improve wound healing. Using a collagen-based hydrogel (cHG) capable of cellular support previously developed by our laboratory, we hypothesize that our hydrogel will increase the speed of wound healing by providing a 3-dimensional framework for cellular support, increasing angiogenesis and cell-proliferation at the wound bed. METHODS: Two, 10-mm excisional wounds were created over the dorsum of 12 male, genetically modified Zucker diabetic rats. Wounds were splinted open to limit healing by wound contracture. One wound was treated with an occlusive dressing (OD), whereas the adjacent wound was treated with an OD plus cHG. Occlusive dressings were changed every other day. Hydrogel was applied on day 2 and every 4 days after until complete wound closure. Rate of wound closure was monitored with digital photography every other day. Wounds were harvested at days 10 and 16 for histological and immunohistochemical analysis. RESULTS: Wound closure was significantly faster in cHG-treated wounds compared with OD-treated wounds. By day 10, cHG-treated wounds achieved 63% wound closure, compared with 55% wound closure in OD-treated wounds (P < 0.05). By day 16, cHG-treated wounds achieved 84% wound closure, compared with 68% wound closure in OD-treated wounds (P < 0.05).Histologically, wound depth was not different between the cHG and OD groups on days 10 and 16. However, wound length was significantly less in the cHG group compared with the OD group (P < 0.05) consistent with digital photographic analysis. Immunohistochemical analysis for RECA-1 demonstrated that blood vessel density in the wound bed was 2.3 times higher in the cHG group compared with the OD group (P = 0.01) on day 16. Cell proliferation was 3.8 times higher in the cHG group versus the OD group (P < 0.05) on day 10. CONCLUSIONS: Collagen-based hydrogel-treated wounds demonstrated significantly improved healing compared with control. The thermoresponsive feature of collagen hydrogel and its structural stability at body temperature demonstrate promising clinical potential as a vehicle for the delivery of therapeutic cells to the wound bed.

Homing of Adipose-Derived Stem Cells to a Tendon-Derived Hydrogel: A Potential Mechanism for Improved Tendon-Bone Interface and Tendon Healing.

PURPOSE: Tendons are difficult to heal owing to their hypocellularity and hypovascularity. Our laboratory has developed a tendon-derived hydrogel (tHG) that significantly improves tendon healing in an animal model. We hypothesized that a potential mechanism for improved healing with tHG is through the attraction of systemic stem cells. METHODS: Homing of systemic adipose-derived stem cells (ADSCs) to tendon injuries was assessed with acute and chronic injury models. Injury sites were treated with saline or tHG, and animals given a tail vein injection (TVI) of labeled ADSCs 1 week after treatment. One week following TVI, rats were harvested for histology. To further evaluate a potential difference in homing to tHG, a subcutaneous injection (SQI) model was used. Rats were treated with an SQI of saline, silicone, ADSCs in media, tHG, tHG + fibroblasts (FBs), or tHG + ADSCs on day 0. One week after SQI, rats underwent TVI with labeled ADSCs. Samples were harvested 2 or 3 weeks after SQI for analysis. Flow cytometry confirmed homing in the SQI model. RESULTS: Systemically delivered ADSCs homed to both acute tendon and chronic tendon-bone interface (TBI) injury sites. Despite their presence at the injury site, there was no difference in the number of macrophages, amount of cell proliferation, or angiogenesis 1 week after stem cell delivery. In an SQI model, ADSCs homed to tHG. There was no difference in the number of ADSCs homing to tHG alone versus tHG + ADSCs. However, there was an increase in the number of living cells, general immune cells, and T-cells present at tHG + ADSC versus tHG alone. CONCLUSIONS: The ADSCs home to tendon injury sites and tHG. We believe the attraction of additional systemic ADSCs is one mechanism for improved tendon and TBI healing with tHG. CLINICAL RELEVANCE: Treatment of tendon and TBI injuries with tHG can augment healing via homing of systemic stem cells.

A Novel Technology for Free Flap Monitoring: Pilot Study of a Wireless, Biodegradable Sensor.

BACKGROUND: Accurate monitoring of free flap perfusion after complex reconstruction is critical for early recognition of flap compromise. Surgeons use a variety of subjective and objective measures to evaluate flap perfusion postoperatively. However, these measures have some limitations. We have developed a wireless, biodegradable, and flexible sensor that can be applied to real-time postoperative free flap monitoring. Here we assess the biocompatibility and function of our novel sensor. METHODS: Seven Sprague-Dawley (SD) rats were used for biocompatibility studies. The sensor was implanted around the femoral artery near the inguinal ligament on one leg (implant side) and sham surgery was performed on the contralateral leg (control side). At 6 and 12 weeks, samples were harvested to assess the inflammation within and around the implant and artery. Two animals were used to assess sensor function. Sensor function was evaluated at implantation and 7 days after the implantation. Signal changes after venous occlusion were also assessed in an epigastric artery island flap model. RESULTS: In biocompatibility studies, the diameter of the arterial lumen and intima thickness in the implant group were not significantly different than the control group at the 12-week time point. The number of CD-68 positive cells that infiltrated into the soft tissue, surrounding the femoral artery, was also not significantly different between groups at the 12-week time point. For sensor function, accurate signaling could be recorded at implantation and 7 days later. A change in arterial signal was noted immediately after venous occlusion in a flap model. CONCLUSION: The novel wireless, biodegradable sensor presented here is biocompatible and capable of detecting arterial blood flow and venous occlusion with high sensitivity. This promising new technology could combat the complications of wired sensors, while improving the survival rate of flaps with vessel compromise due to its responsive nature.

Upper Extremity Angiographic Patterns in Systemic Sclerosis: Implications for Surgical Treatment.

PURPOSE: Conventional angiography is often used in the preoperative work-up of hand surgery patients with systemic sclerosis. The goal of this study was to propose a classification system based on the pattern of arterial involvement in a series of upper extremity angiograms. The authors hypothesized that this classification system would demonstrate high inter- and intrarater reliability. METHODS: A retrospective review of 110 upper extremity angiograms in patients with systemic sclerosis (obtained between 1996 and 2017) was performed. Images were classified into 4 types based on the patency of the radial and ulnar arteries at the wrist, and into 3 subtypes based on the patency of the superficial and deep palmar arches. Classification reliability was compared with Fleiss' Kappa (for inter-rater) and Cohen's (for intrarater) coefficient between 4 fellowship-trained hand surgeons and a hand fellow. RESULTS: The inter-rater reliability between all 5 observers using types alone was 0.83 (0.80-0.85), whereas the inter-rater reliability using subtypes was 0.64 (confidence interval [CI] 95%, 0.62-0.65). The intrarater reliability using types alone ranged from 0.80 to 0.95, whereas intrarater reliabilities using subtypes were 0.81 (CI 95%, 0.72-0.90), 0.78 (CI 95%, 0.69-0.87), 0.87 (CI 95%, 0.80-0.95), 0.64 (CI 95%, 0.53-0.75), and 0.92 (CI 95%, 0.86-0.98) for the 4 attendings and a hand fellow, respectively. Fifty-seven percent of angiograms were interpreted as having loss of ulnar artery patency at the wrist (type 2) with 77% having additional loss of superficial palmar arch patency (type 2A). CONCLUSIONS: This large series of angiograms in patients with systemic sclerosis demonstrates a classification system for conventional angiography that shows high inter-rater and intrarater reliability using type alone. When subtypes were used, the inter-rater and intrarater reliabilities decreased to moderate and moderate-to-high, respectively. CLINICAL RELEVANCE: This study represents the first step in establishing a classification system that, by grouping patients with similar angiogram findings, may allow for targeted research into risk stratification, monitoring, and treatment in systemic sclerosis.

Human Tendon-Derived Collagen Hydrogel Significantly Improves Biomechanical Properties of the Tendon-Bone Interface in a Chronic Rotator Cuff Injury Model.

PURPOSE: Poor healing of the tendon-bone interface (TBI) after rotator cuff (RTC) tears leads to high rates of recurrent tear following repair. Previously, we demonstrated that an injectable, thermoresponsive, type I collagen-rich, decellularized human tendon-derived hydrogel (tHG) improved healing in an acute rat Achilles tendon injury model. The purpose of this study was to investigate whether tHG enhances the biomechanical properties of the regenerated TBI in a rat model of chronic RTC injury and repair. METHODS: Tendon hydrogel was prepared from chemically decellularized human cadaveric flexor tendons. Eight weeks after bilateral resection of supraspinatus tendons, repair of both shoulders was performed. One shoulder was treated with a transosseous suture (control group) and the other was treated with a transosseous suture plus tHG injection at the repair site (tHG group). Eight weeks after repair, the TBIs were evaluated biomechanically, histologically, and via micro-computed tomography (CT). RESULTS: Biomechanical testing revealed a larger load to failure, higher stiffness, higher energy to failure, larger strain at failure, and higher toughness in the tHG group versus control. The area of new cartilage formation was significantly larger in the tHG group. Micro-CT revealed no significant difference between groups in bone morphometry at the supraspinatus tendon insertion, although the tHG group was superior to the control. CONCLUSIONS: Injection of tHG at the RTC repair site enhanced biomechanical properties and increased fibrocartilage formation at the TBI in a chronic injury model. CLINICAL RELEVANCE: Treatment of chronic RTC injuries with tHG at the time of surgical treatment may improve outcomes after surgical repair.

Psychiatric and Substance Use Disorders and Their Association With Clinical Outcomes in Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome.

BACKGROUND AND OBJECTIVE: Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are life-threatening conditions that send nearly 180,000 patients to the intensive care unit each year, with mortality rates up to 5-10%. Little is known about the impact of concurrent psychiatric disorders on specific DKA/HHS outcomes. Identifying these relationships offers opportunities to improve clinical management, treatment planning, and mitigate associated morbidity and mortality. METHODS: We conducted a retrospective review including adult DKA/HHS admissions within a large Massachusetts hospital system from 2010 to 2019. We identified patients admitted inpatient for DKA or HHS, then filtered by International Classification of Disease-9-CM and International Classification of Disease-10-CM codes for psychiatric diagnoses that were present in patients electronic medical record at any point in this observational period. Outcomes included the number of inpatient admissions for DKA/HHS, age of death, rates of discharging against medical advice (AMA) from any inpatient admission, and end-stage renal disease/dialysis status. Multivariate regression was conducted using R software to control for variables across patients and evaluate relationships between outcomes and concurrent psychiatric disorders. Significance was set at P < 0.05. RESULTS: Seven thousand seven hundred fifty-six patients were admitted for DKA or HHS, 66.9% of whom had a concurrent psychiatric disorder. Of these patients, 54.5% were male, 70.4% were White, and they had an average age of 61.6 years. This compares with 26.1% with concurrent psychiatric condition within the general diabetes population, 52.1% of whom were male, 72.1% were White, and an average age of 68.2 years. A concurrent psychiatric disorder was associated with increased odds of rehospitalization (adjusted odds ratio [aOR] = 1.62 95% confidence interval [CI] 1.35-1.95, P < 0.001), of being diagnosed with end-stage renal disease and on dialysis (aOR = 1.02 95% CI 1.002-1.035, P = 0.02), and of leaving AMA (aOR = 6.44 95% CI 4.46-9.63, P < 0.001). The average age of death for those with a concurrent psychiatric disorder had an adjusted mean difference in years of -7.5 years (95% CI -9.3 to 5.8) compared to those without a psychiatric disorder. CONCLUSIONS: Of patients with DKA/HHS, 66.9% have a concurrent psychiatric disorder. Patients with a concurrent psychiatric disorder admitted for DKA/HHS were more likely to have multiple admissions, to leave AMA, to be on renal dialysis, and to have a lower age of mortality.

Analysis of Cell-seeded, Collagen-rich Hydrogel for Wound Healing.

Our laboratory has previously developed a novel collagen-rich hydrogel (cHG), which significantly increases the speed of wound healing in diabetic rats. METHODS: In this study, we examine the in vitro survival and migration of fibroblasts, endothelial cells, and adipose-derived stem cells in a novel cHG. Furthermore, we test the ability of adipose-derived stem cell-seeded cHG to support cell survival and accelerate healing in vivo. RESULTS: In vitro, cell survival within the cHG was retained for 25 days. We were unable to detect cellular migration into, out of, or through cHG. In the in vivo model, bioluminescence of stem cells seeded within the cHG in diabetic rat wounds was detected until day 10. Rate of wound closure was higher for cHG plus adipose-derived stem cells versus control from day 2 until day 16 and significant on days 6, 8, and 12 (P < 0.05). This significant difference was also observed on day 16 by histology (P ≤ 0.05). CONCLUSIONS: We conclude that cHG is a good candidate for delivering adipose-derived stem cells, endothelial cells, and fibroblasts to wounds. Future studies will determine whether the delivery of combinations of different cell lines in cHG further enhances wound healing.

Augmentation of chronic rotator cuff healing using adipose-derived stem cell-seeded human tendon-derived hydrogel.

Rotator cuff (RTC) repair outcomes are unsatisfactory due to the poor healing capacity of the tendon bone interface (TBI). In our preceding study, tendon hydrogel (tHG), which is a type I collagen rich gel derived from human tendons, improved biomechanical properties of the TBI in a rat chronic RTC injury model. Here we investigated whether adipose-derived stem cell (ASC)-seeded tHG injection at the repair site would further improve RTC healing. Rats underwent bilateral supraspinatus tendon detachment. Eight weeks later injured supraspinatus tendons were repaired with one of four treatments. In the control group, standard transosseous suture repair was performed. In the ASC, tHG, tHGASC groups, ASC in media, tHG, and ASC-seeded tHG were injected at repair site after transosseous suture repair, respectively. Eight weeks after repair, the TBI was evaluated biomechanically, histologically, and via micro CT. Implanted ASCs were detected in ASC and tHGASC groups 7 weeks after implantation. ACS implantation improved bone morphometry at the supraspinatus insertion on the humerus. Injection of tHG improved biomechanical properties of the repaired TBI. RTC healing in tHGASC group was significantly better than control but statistically equivalent to the tHG group based on biomechanical properties, fibrocartilage area at the TBI, and bone morphometry at the supraspinatus insertion. In a rat RTC chronic injury model, no biomechanical advantage was gained with ASC augmentation of tHG. Clinical Significance: Tendon hydrogel augmentation with adipose derived stem cells does not significantly improve TBI healing over tHG alone in a chronic rotator cuff injury model. © 2019 Orthopaedic Research Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Use of string test and stool specimens to diagnose pulmonary tuberculosis.

BACKGROUND: The Xpert MTB/RIF (MTB/RIF) test has advanced the field of tuberculosis (TB) diagnostics; however, depending on age and HIV status, 10-85% of individuals with presumed pulmonary TB (PTB) are unable to produce sputum. METHODS: The feasibility of using MTB/RIF and culture on stool and string test specimens from 13 adult patients with presumed PTB was studied. RESULTS: The string test was well tolerated with a median Wong Baker Faces score of 2. The string test had 100% sensitivity and specificity by MTB/RIF and 87.5% sensitivity and 100% specificity by culture. In stool, Mycobacterium tuberculosis DNA was detected in all cases of culture-confirmed PTB. CONCLUSION: The string test and stool provide diagnostic specimens that warrant further investigation.

Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: a systematic review and meta-analysis.

BACKGROUND: Microbiological confirmation of childhood tuberculosis is rare because of the difficulty of collection of specimens, low sensitivity of smear microscopy, and poor access to culture. We aimed to establish summary estimates for sensitivity and specificity of of the Xpert MTB/RIF assay compared with microscopy in the diagnosis of pulmonary tuberculosis in children. METHODS: We searched for studies published up to Jan 6, 2015, that used Xpert in any setting in children with and without HIV infection. We systematically reviewed studies that compared the diagnostic accuracy of Xpert MTB/RIF (Xpert) with microscopy for detection of pulmonary tuberculosis and rifampicin resistance in children younger than 16 years against two reference standards-culture results and culture-negative children who were started on anti-tuberculosis therapy. We did meta-analyses using a bivariate random-effects model. FINDINGS: We identified 15 studies including 4768 respiratory specimens in 3640 children investigated for pulmonary tuberculosis. Culture tests were positive for tuberculosis in 12% (420 of 3640) of all children assessed and Xpert was positive in 11% (406 of 3640). Compared with culture, the pooled sensitivities and specificities of Xpert for tuberculosis detection were 62% (95% credible interval 51-73) and 98% (97-99), respectively, with use of expectorated or induced sputum samples and 66% (51-81) and 98% (96-99), respectively, with use of samples from gastric lavage. Xpert sensitivity was 36-44% higher than was sensitivity for microscopy. Xpert sensitivity in culture-negative children started on antituberculosis therapy was 2% (1-3) for expectorated or induced sputum. Xpert's pooled sensitivity and specificity to detect rifampicin resistance was 86% (95% credible interval 53-98) and 98% (94-100), respectively. INTERPRETATION: Compared with microscopy, Xpert offers better sensitivity for the diagnosis of pulmonary tuberculosis in children and its scale-up will improve access to tuberculosis diagnostics for children. Although Xpert helps to provide rapid confirmation of disease, its sensitivity remains suboptimum compared with culture tests. A negative Xpert result does not rule out tuberculosis. Good clinical acumen is still needed to decide when to start antituberculosis therapy and continued research for better diagnostics is crucial. FUNDING: WHO, Global TB Program of Texas Children's Hospital.