Comparison of Fusion Rates/Complications Between Different Types of Thumb Metacarpophalangeal Fusion Techniques.

BACKGROUND: Thumb metacarpophalangeal (MP) fusion is generally successful; however, complications have been reported to occur in 0% to 30% of cases, whereas nonunion rates vary by method but, overall, are reported to occur in 0% to 15% of cases. Many fixation techniques have been described, but there is no consensus on the optimal fusion technique. Our goal was to compare complication and union rates of different thumb MP arthrodesis techniques. METHODS: We performed a retrospective review of patients who underwent primary thumb MP fusion between 2000 and 2022. Patients who underwent revision fusion, fusion for infection, or amputation were excluded. Fusions of MP joints of other fingers were also excluded. Data collection consisted of demographic data, complications, time to fusion, rate of delayed union and rate of nonunion. Five different fusion constructs were evaluated during our study period: staples, Kirschner wires (K-wires), cerclage, K-wires with cerclage, and intramedullary screw. RESULTS: Forty-seven patients underwent fusion with staples, 16 with K-wires, 14 with cerclage, 9 with K-wires and cerclage, and 6 with an intramedullary screw. The individual complication and nonunion rates differed significantly among the groups with the intramedullary screw group having a statistically higher rate of nonunion (P = .004). Furthermore, smoking, diabetes, and being overweight were associated with nonunions. CONCLUSION: Union rates were significantly lower in patients treated with an intramedullary screw and those who are smokers, diabetics, and/or overweight. Caution should be exercised when using intramedullary screw fixation for MP fusion, especially in patients with these comorbidities.

Canal Fill of the Forearm Bones When Placing Intramedullary Nails in the Pediatric and Adolescent Populations.

BACKGROUND: In the lower extremity, studies have suggested an optimal nail diameter to medullary canal diameter (ND/MCD) ratio to minimize postoperative complications. The goal of this study was to determine whether a correlation exists between the occurrence of complications, angulation, and range of motion and the ratio of the ND/MCD in the upper extremity. METHODS: A total of 85 radius and ulna fractures treated with flexible intramedullary nails had ND/MCD ratios measured. Random-effects models were developed to determine the association between complications and ND/MCD ratio, angulation and ND/MCD ratio, and range of motion and ND/MCD ratio. The results were reported for unadjusted models and adjusted models. RESULTS: Of the 85 forearm fractures treated with intramedullary nailing, there were 3 complications. The average follow-up was 6 months. The ND/MCD ratios were categorized as <0.50, 0.50 to 0.59, and ≥0.60. There was not a significant association between the different ratios and angulation, or risk of complication. There was an association between the ND/MCD ratio ≥0.60 and decreased pronation of -1.58° (-2.77° to -0.38°) and supination of -2.68° (-4.91° to -0.46°) (P < .05). CONCLUSION: This study found that there was not an association between the nail to canal diameter ratio and postoperative angulation in forearm fractures treated with flexible intramedullary nails. When choosing a flexible nail for forearm fractures, there does not appear to be an optimal ratio; it is therefore reasonable to use the ND that passes more easily.

Reliability, validity, and responsiveness of a novel subscapularis outcome score: the Baltimore Orthopedic Subscapularis Score.

Background: Available surveys that evaluate shoulder strength and pain often combine rotator cuff muscles making the test unable to differentiate subscapularis tears from other pathology including concomitant supraspinatus, infraspinatus tears. The purpose of this study was to validate a subscapularis-specific shoulder survey (Baltimore Orthopedic Subscapularis Score) as a viable clinical outcome assessment through analysis of psychometric properties. Methods: A 5-question survey was given to a study population of 390 patients, 136 of whom had full thickness rotator cuff tears with a minimum score of 5 (better) and a maximum score of 25 (worse). Surveys were given during the initial consultation, preoperative visit, and postoperative visit. Content validity, construct validity, test-retest reliability, responsiveness to change, internal consistency, and minimal clinically important difference using distribution and anchor-based methods were determined for our subscapularis function survey. Results: A high correlation was reported on test-retest reliability (intraclass correlation coefficient = 0.89). An acceptable internal consistency was reported for all patients surveyed (Cronbach alpha = 0.91). Floor and ceiling effects for patients with rotator cuff pathology were minimized (1% for both). Patients with an isolated subscapularis tear scored worse than supraspinatus/infraspinatus tears and exhibited similar dysfunction as patients with a supraspinatus/infraspinatus/subscapularis tear. An acceptable construct validity was reported with subscapularis-involved tears demonstrating higher scores with significance (P < .05). There was excellent responsiveness to change with a standardized response mean of 1.51 and effect size of 1.27 (large > 0.8). The minimal clinically important difference using a distribution and anchor-based method was 4.1 and 4.6, respectively. Among patients with rotator cuff tears in this population, a score of 22 or higher predicts a subscapularis tear 75% of the time, in spite of its low overall prevalence. Conclusion: The subscapularis shoulder score demonstrated acceptable psychometric performance for outcomes assessment in patients with rotator cuff disease. This survey can be used as an effective clinical tool to assess subscapularis function.

Management of vasopressor induced ischemia.

PURPOSE: We evaluated a cohort of patients who developed vasopressor-induced limb ischemia and the management options to prevent progression or minimize morbidity of digital necrosis. METHODS: We reviewed all current literature on pressor-induced limb ischemia and report options for the management of patients requiring vasopressors who developed limb ischemia. We then retrospectively reviewed presentation, treatment, and short-term outcomes for patients at our tertiary referral academic medical center that developed this complication. Finally, we recommend guidelines for the tiered management of these complex patients. RESULTS: Thirty-six patients were included. Twenty-six patients (72%) required resuscitation with more than one vasopressor. Vasopressors were initiated for septic-shock (52.7%), cardiogenic-shock (16.7%), hypovolemic-shock (13.9%), acute transplant rejection (13.9%), and neurogenic-shock (2.8%). According to the tiered management recommendations, patients were managed with phase 1 care (19%), phase 2 care (8.3%), phase 3 care (50%) or phase 4 care (5.6%). The patient expired in the acute setting in 13.9% of cases. CONCLUSION: Life-saving vasopressors risk digital ischemia and necrosis. Early recognition, reporting, and treatment of this complication are important in minimizing morbidity. Using a tiered approach helps organize the healthcare team's management of this iatrogenic complication while respecting the treatment paradigm of "life over limb," and may be safely performed with acceptable outcomes.

FLT3-ITD cooperates with Rac1 to modulate the sensitivity of leukemic cells to chemotherapeutic agents via regulation of DNA repair pathways.

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm, and patients with an internal tandem duplication (ITD) mutation of the FMS-like tyrosine kinase-3 (FLT3) receptor gene have a poor prognosis. FLT3-ITD interacts with DOCK2, a G effector protein that activates Rac1/2. Previously, we showed that knockdown of DOCK2 leads to decreased survival of FLT3-ITD leukemic cells. We further investigated the mechanisms by which Rac1/DOCK2 activity affects cell survival and chemotherapeutic response in FLT3-ITD leukemic cells. Exogenous expression of FLT3-ITD led to increased Rac1 activity, reactive oxygen species, phosphorylated STAT5, DNA damage response factors and cytarabine resistance. Conversely, DOCK2 knockdown resulted in a decrease in these factors. Consistent with the reduction in DNA damage response factors, FLT3-ITD cells with DOCK2 knockdown exhibited significantly increased sensitivity to DNA damage response inhibitors. Moreover, in a mouse model of FLT3-ITD AML, animals treated with the CHK1 inhibitor MK8776 + cytarabine survived longer than those treated with cytarabine alone. These findings suggest that FLT3-ITD and Rac1 activity cooperatively modulate DNA repair activity, the addition of DNA damage response inhibitors to conventional chemotherapy may be useful in the treatment of FLT3-ITD AML, and inhibition of the Rac signaling pathways via DOCK2 may provide a novel and promising therapeutic target for FLT3-ITD AML.

The Adult Monteggia Fracture: Patterns and Incidence of Annular Ligament Incarceration Among 121 Cases at a Single Institution Over 19 Years.

PURPOSE: The purposes of this study were to identify the relative frequency of Monteggia fracture patterns and to investigate the required frequency of open reduction of the proximal radiocapitellar joint. METHODS: We identified 121 Monteggia fractures at a Level I trauma center from 1996 to 2015 and included 119 in this study. These fractures were identified using a database search for the appropriate International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes as well as individual surgeons' logs. Two fellowship-trained hand surgeons reviewed the identified patients' x-rays and operative notes. Each fracture was classified using Bado's original description, excluding transolecranon and Monteggia variants. RESULTS: Bado I lesion represented 68% (81 of 119) of Monteggia fractures. Annular ligament incarceration preventing radial head reduction occurred in approximately 17% (14 of 81) of this Bado type. Revision fixation of the ulna was not necessary (none of 119 cases) and functional range of motion (average arc, 117°) was recovered in most patients. The reoperation rate of 20% (23 of 119) was related to the severity of the presenting injury and hardware prominence. CONCLUSIONS: Most radial head dislocations associated with Monteggia fractures occur anteriorly and will reduce with anatomic plating of the ulna. In cases where the radial head fails to reduce, entrapment of the annular ligament can be expected and open reduction is required. Revision fixation of the ulna to achieve reduction of the radial head is uncommon in our experience. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Radiographic predictors of symptomatic screw removal after retrograde femoral nail insertion.

INTRODUCTION: Removal of symptomatic implants is a common procedure performed by orthopaedic trauma surgeons. No guidance is available regarding which factors contribute to the likelihood of an implant becoming symptomatic. Our objective was to determine whether radiographic parameters associated with distal interlocks in retrograde femoral nails are associated with the rate of symptomatic screw removal. PATIENTS AND METHODS: We conducted a retrospective review at a Level I trauma center. Study patients (n=442) had femoral fractures treated with retrograde intramedullary nails from 2007 to 2014 and at least 1year of follow-up. The main outcome measurement was symptomatic distal screw removal as predicted by radiographic parameters. RESULTS: Symptomatic screw removal occurred in 12% of the patients. Increased distance between the most distal screw and the articular surface of the femur significantly reduced likelihood of symptomatic screw removal. A cutoff of 40mm from the articular block was predictive of removal (≥40mm, 0% removal; <40mm, 18% removal, p<0.0001). In patients with distal screws placed within 40mm of the articular surface of the femur, a ratio of screw length to distance between medial and lateral femoral cortices that was ≥1 was a strong predictor of symptomatic screw removal (area under Receiver Operating Characteristic curve, 0.75; p<0.0001). CONCLUSIONS: More distal screws and screws that radiographically extend to or beyond the medial cortex are more likely to cause pain and require removal in femoral fractures treated with retrograde intramedullary nails. We identified a specific distance from the joint (<40mm) and a ratio of screw length to bone width (≥1) that significantly increased the likelihood of symptomatic screw removal. Clinicians can use these data to inform patients of the likely risk of implant removal and perhaps to better guide placement and length of screws when the clinical scenario allows some flexibility in location and length of screws.

Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia-cell cycle dual reporter.

Although aerobic glycolysis provides an advantage in the hypoxic tumor microenvironment, some cancer cells can also respire via oxidative phosphorylation. These respiring ("non-Warburg") cells were previously thought not to play a key role in tumorigenesis and thus fell from favor in the literature. We sought to determine whether subpopulations of hypoxic cancer cells have different metabolic phenotypes and gene-expression profiles that could influence tumorigenicity and therapeutic response, and we therefore developed a dual fluorescent protein reporter, HypoxCR, that detects hypoxic [hypoxia-inducible factor (HIF) active] and/or cycling cells. Using HEK293T cells as a model, we identified four distinct hypoxic cell populations by flow cytometry. The non-HIF/noncycling cell population expressed a unique set of genes involved in mitochondrial function. Relative to the other subpopulations, these hypoxic "non-Warburg" cells had highest oxygen consumption rates and mitochondrial capacity consistent with increased mitochondrial respiration. We found that these respiring cells were unexpectedly tumorigenic, suggesting that continued respiration under limiting oxygen conditions may be required for tumorigenicity.

Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells.

Because MYC plays a causal role in many human cancers, including those with hypoxic and nutrient-poor tumor microenvironments, we have determined the metabolic responses of a MYC-inducible human Burkitt lymphoma model P493 cell line to aerobic and hypoxic conditions, and to glucose deprivation, using stable isotope-resolved metabolomics. Using [U-(13)C]-glucose as the tracer, both glucose consumption and lactate production were increased by MYC expression and hypoxia. Using [U-(13)C,(15)N]-glutamine as the tracer, glutamine import and metabolism through the TCA cycle persisted under hypoxia, and glutamine contributed significantly to citrate carbons. Under glucose deprivation, glutamine-derived fumarate, malate, and citrate were significantly increased. Their (13)C-labeling patterns demonstrate an alternative energy-generating glutaminolysis pathway involving a glucose-independent TCA cycle. The essential role of glutamine metabolism in cell survival and proliferation under hypoxia and glucose deficiency makes them susceptible to the glutaminase inhibitor BPTES and hence could be targeted for cancer therapy.

Therapeutic targeting of cancer cell metabolism.

In 1927, Otto Warburg and coworkers reported the increased uptake of glucose and production of lactate by tumors in vivo as compared with normal tissues. This phenomenon, now known as the Warburg effect, was recapitulated in vitro with cancer tissue slices exhibiting excessive lactate production even with adequate oxygen. Warburg's in vivo studies of tumors further suggest that the dependency of tumors in vivo on glucose could be exploited for therapy, because reduction of arterial glucose by half resulted in a four-fold reduction in tumor fermentation. Recent work in cancer metabolism indicates that the Warburg effect or aerobic glycolysis contributes to redox balance and lipid synthesis, but glycolysis is insufficient to sustain a growing and dividing cancer cell. In this regard, glutamine, which contributes its carbons to the tricarboxylic acid (TCA) cycle, has been re-discovered as an essential bioenergetic and anabolic substrate for many cancer cell types. Could alterations in cancer metabolism be exploited for therapy? Here, we address this question by reviewing current concepts of normal metabolism and altered metabolism in cancer cells with specific emphasis on molecular targets involved directly in glycolysis or glutamine metabolism.