Impact of Tourniquet Use in Major Lower Limb Amputation: A Systematic Review and Meta-analysis.

OBJECTIVE: Intra-operative blood loss is a significant complication of major lower limb amputation (MLLA). This systematic review and meta-analysis assessed the effect of tourniquet use on patients undergoing amputation. DATA SOURCES: Embase, MEDLINE, and Cochrane databases were searched from inception to April 2024. REVIEW METHODS: Inclusion criteria were any study design assessing MLLA with and without tourniquet use. Primary outcomes were peri-operative blood loss and transfusion requirements. Secondary outcomes were operative duration, surgical site infection, stump revision, and mortality. Articles were screened and data extracted independently by two reviewers, then pooled using random effects meta-analysis, and presented with their GRADE certainty. Risk of bias was assessed using ROBINS-I and Cochrane RoB 2 tools. RESULTS: Seven studies (one randomised controlled trial [RCT] and six cohort studies) were included, totalling 1 018 limbs (412 tourniquet, 606 non-tourniquet). Intra-operative blood loss was lower with tourniquet use (mean difference [MD] -192.09 mL; 95% confidence interval [CI] -291.67 - -92.52; p < .001); however, there was no significant difference in total blood loss measured over the first three to four post-operative days (MD -254.66 mL; 95% CI -568.12 - 58.80; p = .11). Post-operative haemoglobin drop was lower for tourniquet patients (MD -0.55 g/dL; 95% CI -0.80 - -0.31; p < .001). The odds ratio (OR) for requiring blood transfusion was 0.65 (95% CI 0.38 - 1.11; p = .11) for tourniquet vs. non-tourniquet patients, with no significant difference in the number of units transfused per patient (MD -0.35, 95% CI -0.72 - 0.03; p = .070). Operation duration was shorter with tourniquet use (MD -8.69 minutes, 95% CI -15.95 - -1.42; p = .020). There was no significant difference in rates of surgical site infection (OR 1.07, 95% CI 0.60 - 1.90; p = .82), stump revision (OR 0.71, 95% CI 0.43 - 1.16; p = .17), or death (OR 0.80, 95% CI 0.49 - 1.30; p = .36). GRADE certainty was low or very low for all outcomes. CONCLUSION: Tourniquet use may be associated with reduced post-operative haemoglobin drop and operative duration, without negative consequences on stump infection, revision, and mortality. However, most data are observational. Further RCTs are needed to generate higher quality evidence.

Patient Perceptions of Surveillance of Small Abdominal Aortic Aneurysms in the Over 85s.

BACKGROUND: Recently instigated local practice for patients with small abdominal aortic aneurysms (AAAs) involves contacting all patients, aged ≥85 years, to discuss with them the advantages and disadvantages of removal from surveillance. However, reasons why patients opt to remain on, or come off, surveillance, are currently unknown. The present study's objective is to explore patient perception of surveillance decision-making. METHODS: A mixed-methods exploratory evaluation was undertaken using patient feedback obtained from a telephone survey. All patients aged ≥85 years, who had a consultation regarding ongoing surveillance of small AAAs (30-49 mm), and consented, were contacted by researchers, who conducted semi-structured interviews concerning factors influencing decision-making. RESULTS: A total of 24 patients (20 male; mean age = 86.9 years) were interviewed; 16 of 24 (66%) had opted to remain on surveillance, with no age difference between those opting in or out. Most felt surveillance was important (91%), and that it made them feel safer (73%). The majority (73%) thought they knew what happened when their AAA reached threshold (5.5 cm), what happened when a threshold AAA is not fixed (64%), and how major AAA surgery is (59%). However, actual knowledge was poor: most (91%) correctly understood surgery was major, but 56% thought that threshold AAA meant certain death or rupture; and 38% thought immediate surgery was required. Thematic analysis expounded patients' beliefs regarding surveillance, which were summarized in 3 distinct subgroups: reliance on professionals' opinions, needing peace of mind, and poor understanding. CONCLUSIONS: While most patients find surveillance reassuring, patient knowledge of AAA management at threshold is poor, potentially impacting surveillance decision-making. Elderly patients, with small AAAs contemplating ongoing surveillance, need to be better informed about AAA management at threshold to support shared decision-making.

Emergency medicine pharmacist interventions reducing exposure to costs (EMPIRE-C).

INTRODUCTION: Emergency Medicine (EM) pharmacists are considered essential healthcare providers in the Emergency Department (ED). Limited data are available representing the types of interventions performed by ED pharmacists, especially in community-based health systems. METHODS: Retrospective, multi-centered, observational review of documented EM clinical pharmacist interventions into the electronic medical record (EMR) across five separate EDs between July 1, 2020 and June 30, 2021. Interventions were separated into three categories: ED Intervention, ED Outpatient Culture Review, and ED Discharge Antimicrobial Review. Interventions with supporting literature related to cost avoidance were also analyzed. RESULTS: A total of 23,794 interventions were logged by the EM pharmacy team between the three categories. Of those, 9181 were cost avoidance interventions resulting in $5,350,755.63 in total cost avoidance, or $582.81 per intervention. CONCLUSION: EM pharmacists practicing in community settings have a substantial impact on patients as evidenced by the large quantity and variety of interventions logged which also results in significant cost avoidance to the healthcare system.

Ectodermal-Neural Cortex 1 Isoforms Have Contrasting Effects on MC3T3-E1 Osteoblast Mineralization and Gene Expression.

The importance of Wnt pathway signaling in development of bone has been well established. Here we investigated the role of a known Wnt target, ENC1 (ectodermal-neural cortex 1; NRP/B), in osteoblast differentiation. Enc1 expression was detected in mouse osteoblasts, chondrocytes, and osteocytes by in situ hybridization, and osteoblastic expression was verified in differentiating primary cultures and MC3T3-E1 pre-osteoblast cells, with 57 kDa and 67 kDa ENC1 protein isoforms detected throughout differentiation. Induced knockdown of both ENC1 isoforms reduced alkaline phosphatase staining and virtually abolished MC3T3-E1 mineralization. At culture confluence, Alpl (alkaline phosphatase liver/bone/kidney) expression was markedly reduced compared with control cells, and there was significant and coordinated alteration of other genes involved in cellular phosphate biochemistry. In contrast, with 67 kDa-selective knockdown mineralized nodule formation was enhanced and there was a two-fold increase in Alpl expression at confluence. There was enhanced expression of Wnt/ß-catenin target genes with knockdown of both isoforms at this time-point and a five-fold increase in Frzb (Frizzled related protein) with 67 kDa-selective knockdown at mineralization, indicating possible ENC1 interactions with Wnt signaling in osteoblasts. These results are the first to demonstrate a role for ENC1 in the control of osteoblast differentiation. Additionally, the contrasting mineralization phenotypes and transcriptional patterns seen with coordinate knockdown of both ENC1 isoforms vs selective knockdown of 67 kDa ENC1 suggest opposing roles for the isoforms in regulation of osteoblastic differentiation, through effects on Alpl expression and phosphate cellular biochemistry. This study is the first to report differential roles for the ENC1 isoforms in any cell lineage. J. Cell. Biochem. 118: 2141-2150, 2017. © 2016 Wiley Periodicals, Inc.

Acknowledging and Addressing Microaggressions: A Virtual Experiential Learning Approach for Faculty.

Introduction: Although the ACGME and other accrediting organizations are increasingly emphasizing the importance of clinical learning environments that value diversity, equity, and inclusion, faculty development surrounding behavioral skills that promote inclusivity in the learning environment still needs cultivation. We designed a virtual longitudinal faculty development curriculum focused on direct observation, feedback, and practice of behavioral skills to acknowledge and address microaggressions in the learning environment. Methods: We used Kern's six steps of curriculum development to create four voluntary virtual workshops offered twice throughout the academic year, with topics including: (1) recognizing and naming microaggressions, (2) apologizing when harm has been experienced, (3) setting expectations surrounding microaggressions, and (4) debriefing microaggressions. Participant learners included residency program directors, associate program directors, and other leaders across all medical and surgical departments from one institution. Results: Thirty-one faculty from 10 departments participated in this yearlong curriculum. Pre- and postworkshop surveys analyzed participants' self-assessments of confidence and comfort in applying learned skills. Participants were more confident in openly naming bias, delivering expectations surrounding microaggressions, and debriefing microaggressions with learners. Participants also reported greater comfort in apologizing to learners when harm has occurred in public, in person, and electronically. Discussion: To create an inclusive learning environment, faculty can increase their comfort and confidence with addressing bias and microaggressions through practice and feedback. Our curriculum demonstrates how experiential learning allows for continual practice to solidify a new skill.

Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade.

Systemic onset juvenile idiopathic arthritis (SoJIA) represents up to 20% of juvenile idiopathic arthritis. We recently reported that interleukin (IL) 1 is an important mediator of this disease and that IL-1 blockade induces clinical remission. However, lack of specificity of the initial systemic manifestations leads to delays in diagnosis and initiation of therapy. To develop a specific diagnostic test, we analyzed leukocyte gene expression profiles of 44 pediatric SoJIA patients, 94 pediatric patients with acute viral and bacterial infections, 38 pediatric patients with systemic lupus erythematosus (SLE), 6 patients with PAPA syndrome, and 39 healthy children. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared with healthy children. These genes, however, were also changed in patients with acute infections and SLE. An analysis of significance across all diagnostic groups identified 88 SoJIA-specific genes, 12 of which accurately classified an independent set of SoJIA patients with systemic disease. Transcripts that changed significantly in patients undergoing IL-1 blockade were also identified. Thus, leukocyte transcriptional signatures can be used to distinguish SoJIA from other febrile illnesses and to assess response to therapy. Availability of early diagnostic markers may allow prompt initiation of therapy and prevention of disabilities.

Matched pilot study examining cannabis-based dronabinol for acute pain following traumatic injury.

BACKGROUND: To determine whether adjunctive dronabinol, a licensed form of delta-9-tetrahydrocannabinol, reduces opioid consumption when used off-label for managing acute pain following traumatic injury. METHODS: This matched cohort study included patients who were admitted with a traumatic injury between 1 March 2017 and 30 October 2017. The hospital pharmacy database was used to identify patients who received dronabinol (cases), and they were matched 1:1 to patients who did not receive dronabinol (controls) using age, cause of injury and hospital length of stay. The primary outcome, change in opioid consumption, was calculated using morphine milligram equivalents (MME). The change in MME was calculated for cases as total MME over 48 hours with adjunctive dronabinol minus 48 hours prior to dronabinol, and for controls as total MME 48-96 hours from admission minus 0-48 hours from admission. Data are presented as mean and SE or median and IQR. Statistical analysis was performed using paired t-tests and McNemar's tests. RESULTS: There were 66 patients included: 33 cases and 33 matched controls. Dronabinol was initiated 55 (28-107) hours from admission. Cases and controls were well matched. Cases had a significant reduction in opioid consumption with adjunctive dronabinol (-79 (20) MME, p<0.001), while opioid consumption was unchanged for controls (-9 (20) MME, p=0.63). This resulted in a ninefold greater reduction in opioid consumption for cases versus controls that was statistically different between pairs (p=0.02). Nineteen (58%) cases reported using marijuana; in this subset, opioid consumption was reduced with adjunctive dronabinol (-97 (24) MME, p<0.001) versus a non-significant increase in opioid consumption in matched controls (11 (29) MME, p=0.70); difference between groups, p=0.01. CONCLUSIONS: The results of this study suggest adjunctive dronabinol reduces opioid consumption following traumatic injury. The opioid-sparing effect of dronabinol may be greater in patients who are marijuana users. LEVEL OF EVIDENCE: III.

Correction to: Association of rheumatoid arthritis-related autoantibodies with pulmonary function test abnormalities in a rheumatoid arthritis registry.

The publisher regrets that the two sections under the Results omitted inadvertently on the original published version of the above article.

Association of rheumatoid arthritis-related autoantibodies with pulmonary function test abnormalities in a rheumatoid arthritis registry.

INTRODUCTION: We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with abnormalities on pulmonary function tests (PFTs). METHODS: We studied RA serostatus and PFT abnormalities within a RA registry. RA serostatus was assessed by research assays for cyclic citrullinated peptide (CCP) and rheumatoid factor (RF). Outcomes were abnormalities on clinically indicated PFTs, including restriction, obstruction, and diffusion abnormality. Logistic regression was used to obtain ORs and 95% CIs for the PFT abnormalities by RA serologic phenotypes independent of lifestyle and RA characteristics. RESULTS: Among 1272 analyzed subjects, mean age was 56.3 years (SD 14.1), 82.2% were female, and 69.5% were seropositive. There were 100 subjects with abnormal PFTs. Compared with seronegativity, seropositivity was associated with increased odds of any PFT abnormality (multivariable OR 2.29, 95% CI 1.30-4.03). When analyzing type of PFT abnormality, seropositivity was also associated with restriction, obstruction, and diffusion abnormalities; multivariable ORs were 2.48 (95% CI 1.26-4.87), 3.12 (95% CI 1.28-7.61), and 2.30 (95% CI 1.09-4.83), respectively. When analyzing by CCP and RF status, the associations were stronger for RF+ than for CCP+ (any PFT abnormality OR 1.99, 95% CI 1.21-3.27 for RF+ vs. RF-; OR 1.67, 95% CI 1.03-2.69 for CCP+ vs. CCP-) with a dose effect of higher RF titer increasing odds for each PFT abnormality (p for trend < 0.05). CONCLUSIONS: Seropositive RA patients had two-fold increased risk for abnormalities on PFTs performed for clinical indications compared with seronegative RA. Patients with seropositive RA, particularly those with high-titer RF positivity, may be more likely to have obstructive and restrictive abnormalities, independent of smoking.Key points• Due to the known excess pulmonary morbidity/mortality in RA, we studied the relationship of rheumatoid arthritis (RA)-related autoantibodies with pulmonary function test (PFT) abnormalities using a large RA registry.• We evaluated whether presence and levels of cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were associated with restriction, obstruction, and diffusion abnormalities on PFTs among 1272 subjects with RA.• Seropositivity was associated with two-fold increased risk for any PFT abnormality, independent of confounders including smoking. Higher titers of RF conferred greatest risk for all PFT outcomes: obstruction, restriction, and diffusion abnormality.• These results provide evidence that patients with RA should be closely monitored for pulmonary involvement, particularly those with high-titer RF seropositivity.

Smoking Is an Independent Risk Factor of Reoperation Due to Recurrent Lumbar Disc Herniation.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The purpose of the present study is to determine if age, gender, smoking status, and body mass index (BMI) are significant risk factors of symptomatic recurrent lumbar disc herniation (rLDH) leading to reoperation. METHODS: A cohort of 1378 consecutive patients who underwent discectomy for LDH from June 2010 to January 2015 at our institution were included. Patients who underwent reoperation due to rLDH prior to August 2015 were identified. Data on reoperations, age, gender, smoking status, and BMI were collected from our database. A comparison of age, gender, smoking status, and BMI was made between the controls (non-rLDH) and the cases (rLDH group). Binary logistic regression was performed to determine whether age, gender, smoking status, and BMI were independent risk factors for rLDH. RESULTS: Patients in the non-rLDH group (48.2 years) were older than the rLDH group (44.7 years; P = .013). Gender distribution (54.8% vs 48.5% males; P = .222) and BMI (26.6 vs 26.6; P = .458) were similar between the 2 groups. A significantly higher prevalence of smokers was found in the rLDH group (33.1% vs 51.5%; P < .001). Binary logistic regression analysis showed that smoking was an independent risk factor of rLDH (odds ratio = 2.12; 95% confidence interval = 1.39-3.15; P < .001). CONCLUSIONS: Neither age, BMI, nor gender had any statistical significant association with the risk of rLDH. Smoking was associated with higher risk of reoperation due to rLDH.

Transient disturbance in physeal morphology is associated with long-term effects of nitrogen-containing bisphosphonates in growing rabbits.

UNLABELLED: Bisphosphonates have clinical benefit in children with severe osteogenesis imperfecta or osteoporosis and potential benefit in children with Perthes disease or undergoing distraction osteogenesis. However, there is concern about the effects of bisphosphonates on the physis and bone length. In 44 growing rabbits, zoledronic acid caused a transient disruption of physeal morphology, retention of cartilaginous matrix in trabeculae and cortical bone of the metaphysis, and a minor decrement in tibial bone length at maturity. INTRODUCTION: Data from growing animal models suggest that bisphosphonates cause retention of longitudinal cartilaginous septa at the chondro-osseous junction, extension of trabeculae to the metaphyseal-diaphyseal junction, and varying dose-dependent effects on longitudinal growth. However, there is a lack of data regarding effects of intermittent use of nitrogen-containing bisphosphonates on the physis and on tibial length in models reaching maturity. MATERIALS AND METHODS: Contralateral tibias of juvenile rabbits were examined after right tibial distraction osteogenesis from two previous studies. Animals were randomized to receive 0.1 mg/kg zoledronic acid (ZA) IV at 8 weeks of age (ZA*1) or 8 and 10 weeks of age (ZA*2) or saline. Body mass was analyzed from 5 to 44 weeks of age; tibial length and proximal physeal-metaphyseal histology and histomorphometry were analyzed at 8-52 weeks of age. RESULTS: Tibial length was 3% less at 14 weeks of age in the ZA*2-treated versus saline group (p<0.05) in both studies, and this difference persisted at maturity in the long-term study group (26 weeks of age, p<0.05). Total body mass gain from 5 to 26 weeks of age was 14% less in ZA*2-treated than saline animals (p<0.05). Rate of weight gain from 8 to 10 weeks of age was 76% less in ZA*2 compared with saline animals (p<0.05). Radiographs showed radiodense lines in the metaphyses of ZA-treated bones, corresponding to the number of doses. Histologically, lines resulting from the first dose of ZA contained longitudinal cartilaginous matrix cores surrounded by bone, whereas those from the second dose contained spherical cores of matrix caused by transient disruption of physeal morphology after the first dose of ZA. Resorption of these lines at later times was radiographically and histologically evident, but remnants of cartilaginous matrix remained in the cortical bone of ZA-treated animals. CONCLUSIONS: ZA treatment within the final 13.5% of the rabbit tibial growth period caused a transient disruption in physeal morphology and resorption associated with retention of cartilaginous matrix and coinciding with a persistent 3% decrement in tibial length. Disruption of physeal morphology and potential loss of bone length should be considered when administering nitrogen-containing bisphosphonates to children before closure of the major physes.

Zoledronic acid treatment results in retention of femoral head structure after traumatic osteonecrosis in young Wistar rats.

UNLABELLED: Osteonecrosis (ON) of the femoral head in childhood can lead to loss of femoral head architecture and subsequent deformity. When femoral head ON was surgically induced in 24 rats, zoledronic acid treatment and prophylaxis improved sphericity and maintenance of architecture at 6 weeks. This preliminary experiment supports the use of bisphosphonates in childhood ON. INTRODUCTION: We hypothesized that the bisphosphonate zoledronic acid could preserve femoral head structure while allowing bone repair. MATERIALS AND METHODS: Osteonecrosis (ON) was surgically induced in the right femoral head of 24 female Wistar rats. The rats were randomized into three treatment groups and dosed subcutaneously with saline, zoledronic acid (0.1 mg/kg) at 1 and 4 weeks postoperation (ZA post), or zoledronic acid (0.1 mg/kg) given 2 weeks preoperation and at 1 and 4 weeks postoperation (ZA pre-post). After death at 6 weeks postoperation, undecalcified specimens were analyzed by DXA and standardized histomorphometric analysis. RESULTS: Seventy-one percent of saline-operated femoral heads were aspherical (Mose score > 1), whereas only 13% and 0% of operated heads in the ZA-treated groups were aspherical (p < 0.05). DXA-measured bone mineral density in saline-treated femoral heads was reduced by 34% and 43% compared with the ZA-treated groups (p < 0.01). Histomorphometry showed decreases of 12% and 17% in bone volume (BV/TV) in saline groups compared with ZA post and ZA pre-post (p < 0.05), and a decrease in trabecular number (Tb.N) of 18% and 14% (p < 0.05), respectively. Bone formation rate (BFR) was increased by 56% in saline-treated operated heads over ZA post and was 4.8 times increased over the ZA pre-post group (p < 0.05). The differences in BV/TV and Tb.N in treated groups must therefore be caused by a reduction in bone turnover. Observational histology confirmed the retention of necrotic architecture in treated groups. CONCLUSIONS: Zoledronic acid treatment and prophylaxis preserved femoral head architecture after traumatic ON in this rat model at 6 weeks. These data indicate that, by conserving femoral head architecture, bone repair may occur in conjunction with improved femoral head shape.

Transient retention of endochondral cartilaginous matrix with bisphosphonate treatment in a long-term rabbit model of distraction osteogenesis.

UNLABELLED: Bisphosphonates induce major increases in strength of callus in distraction osteogenesis in the short term. Poor understanding of the underlying mechanism, however, raises concerns about long-term consequences. In this long-term study in 32 rabbits, zoledronic acid transiently increased trabeculae by delayed temporal progression of endochondral bone remodeling but did not prevent radiographic completion of bone repair. INTRODUCTION: We hypothesized that bisphosphonate inhibition of osteoclast-mediated resorption would retain bone during repair, producing a larger callus in the short term. However, if remodeling was not restored, completion of the bone repair process in the long term could be jeopardized. MATERIALS AND METHODS: Juvenile rabbits underwent right tibial osteotomy and 2 weeks of distraction, followed by a period of consolidation. Animals received saline (controls) or zoledronic acid (ZA; 0.1 mg/kg at surgery and again 2 weeks later), and distracted tibias were examined by radiograph, DXA, histology, and histomorphometry at 2, 4, 6, 18, and 44 weeks after surgery. RESULTS: Regenerated bone in ZA-treated animals was denser than controls on radiographs at 6 weeks and had more distinct radiodense trabeculae and retention of original cortices at 18 weeks. By 44 weeks, controls and ZA-treated animals were radiographically healed and indistinguishable. Regenerate BMD and BMC increased between 2 and 4 weeks in all animals, with a greater effect in ZA. At 6 weeks, BMD and BMC in ZA-treated animals were 1.6- and 2-fold greater, respectively, than controls (p < 0.01). From 6 to 44 weeks, the control values gradually increased and approached the ZA-treated values. Regenerate bone volume and trabecular number by histomorphometry were from 1.6- to 2-fold greater in ZA-treated animals at 6 and 18 weeks (p < 0.05). Endochondral cartilaginous matrix volume was up to 2.4-fold greater in ZA-treated animals at 2 and 4 weeks (p < 0.05). TRACP+ cells in ZA-treated animals were larger with more nuclei. Mineral apposition rate and osteoblast number and surface were lower in ZA-treated animals at 6 weeks (p < 0.01) but not at later times. CONCLUSIONS: Disruption of TRACP+ cell function by ZA during bone regeneration seems to lead to an accretion of cancellous bone built on a larger endochondral cartilaginous matrix and increased bone mass, consistent with reported increases in short-term callus strength. This increase in bone mass, caused by a delay in remodeling, provided a transient advantage without preventing radiographic completion of the bone repair process in the long term. Noncontinuous treatment with nitrogen-containing bisphosphonates thus can have short-term beneficial effects without preventing long-term bone repair.

Zoledronic acid prevents osteopenia and increases bone strength in a rabbit model of distraction osteogenesis.

UNLABELLED: Prolonged healing times and stress-shielding osteopenia remain problematic in distraction osteogenesis. In this study of 30 rabbits, zoledronic acid increased regenerate volume, mineralization, and tibial strength and prevented osteopenia over a 6-week period. Translation to the clinical setting, if safe, could improve outcomes in distraction osteogenesis in children. INTRODUCTION: Because the external fixators for limb lengthening and reconstruction are designed to control the positions of bone fragments accurately, they also produce stress-shielding effects on the forming regenerate and surrounding bone. Osteopenia, leading to refracture and limitations on rehabilitation, are common consequences, potentially increasing morbidity and detracting from final clinical outcome. MATERIALS AND METHODS: We examined the effect of zoledronic acid on distraction osteogenesis in 42 immature male NZW rabbits. The model chosen results in reliable regenerate formation and stress-shielding osteopenia. Fourteen animals received either Saline, zoledronic acid 0.1 mg/kg at surgery (ZOL), or another dose 2 weeks postoperatively (Redosed ZOL). Rabbits underwent DXA for bone mineral content and bone mineral density in regenerate and surrounding segments of operated and contralateral tibias. After death at 6 weeks, 30 pairs of tibias underwent quantitative computerized tomography (QCT) and four-point bend testing, and 12 were examined by histomorphometry. The study was powered at 0.8 to show differences of 1.3 SDs for mineral and mechanical parameters. RESULTS: Osteopenia observed in tibias of the Saline group was absent in ZOL and Redosed ZOL tibias, the latter exhibiting higher bone mineral density and bone mineral content over contralateral regions (p < 0.01). Regenerate bone mineral content was higher in ZOL and Redosed ZOL versus Saline groups at 4 and 6 weeks (p < 0.01). Cross-sectional area was 49% and 59% greater at 6 weeks in ZOL and Redosed ZOL regenerates compared with the Saline group (p < 0.01). ZOL and Redosed ZOL tibias were 29% and 89% stronger by four-point bending than the Saline group (p < 0.01). Histomorphometry in the regenerate of ZOL and Redosed ZOL groups revealed higher trabecular bone volume and trabecular number compared with the Saline group (p < 0.001). CONCLUSIONS: Zoledronic acid administration led to significantly greater bone area, mineral content, strength, and trabecular number with reduced stress-shielding osteopenia in this model of distraction osteogenesis. These data suggest that intraoperative and postoperative zoledronic acid administration could improve outcomes in children undergoing limb lengthening.

Aluminum accumulation in critically ill children on sucralfate therapy.

BACKGROUND: Sucralfate, used in stress ulcer prophylaxis, contains aluminum, which can be absorbed from the gut. OBJECTIVE: To determine whether toxic serum aluminum levels can develop after short-term sucralfate therapy in critically ill children. DESIGN: Retrospective clinical study. SETTING: Pediatric intensive care unit of a pediatric university hospital. PATIENTS: Nineteen patients receiving mechanical ventilatory support (median age, 5 yrs [range, 0.25-16 yrs]; median weight, 17 kg [range, 3.5-60 kg]). INTERVENTIONS: All patients received sucralfate suspension nasogastrically. Measurements and RESULTS: Serum aluminum concentrations were measured after a short period on sucralfate therapy (median time, 7 days [range, 3-14 days]). There was no correlation between total sucralfate dose received (p =.35) or dose of sucralfate per unit of body weight (p =.55) and serum aluminum. Nine patients received peritoneal dialysis. Serum aluminum levels were higher in the nine patients who received peritoneal dialysis (median aluminum concentration, 2.86 &mgr;mol/L [range, 0.19-12.3 &mgr;mol/L]) than the ten patients not dialyzed (median aluminum concentration, 0.55 &mgr;mol/L [range, 0.18-0.94 &mgr;mol/L]) (p =.001). The peak serum creatinine levels were higher in the dialyzed patients (median creatinine level, 500 &mgr;mol/L [range, 163-910 &mgr;mol/L]) than those not dialyzed (median creatinine level, 98 &mgr;mol/L [range, 36-415 &mgr;mol/L]) (p =.006). There was a trend toward correlation between peak serum creatinine and serum aluminum (p =.06). CONCLUSION: Aluminum accumulation occurs in children with acute renal failure on sucralfate, especially those receiving dialysis. If sucralfate is used in children in renal failure, serum aluminum concentrations should be monitored regularly.

Increased whole blood manganese concentrations observed in children with iron deficiency anaemia.

A prospective observational study was carried out at Alder Hey Children's Hospital, Liverpool, England, UK on children aged 1-6 years attending the pathology department for routine blood tests (n=225). Whole blood manganese concentrations were measured plus the following markers of iron status; haemoglobin, MCV, MCH, RBC count, ferritin, transferrin saturation and soluble transferrin receptors. Multiple regression analysis was performed, with blood manganese as the dependent variable and factors of iron status, age and gender as independent variables. A strong relationship between blood manganese and iron deficiency was demonstrated (adjusted R(2)=34.3%, p<0.001) and the primary contributing factors to this relationship were haematological indices and soluble transferrin receptors. Subjects were categorised according to iron status using serum ferritin, transferrin saturation and haemoglobin indices. Children with iron deficiency anaemia had higher median blood manganese concentrations (16.4 µg/L, range 11.7-42.4, n=20) than children with iron sufficiency (11 µg/L, range 5.9-20.9, n=59, p<0.001). This suggests that children with iron deficiency anaemia may be at risk from manganese toxicity (whole blood manganese >20 µg/L), and that this may lead to neurological problems. Treatment of iron deficiency in children is important both to improve iron status and to reduce the risk of manganese toxicity.

Life-space mobility is associated with frequency of hospitalization in adults with cystic fibrosis.

INTRODUCTION AND OBJECTIVES: The Life-Space Assessment can be used to measure a patient's level of mobility. This study evaluated the relationship between life-space mobility and frequency of hospitalization in the previous year and other clinical markers of health among adults with cystic fibrosis (CF). METHODS: The Life-Space Assessment was administered to ambulatory adults with CF in clinic or by telephone. Life-space mobility was correlated with the most recent forced expiratory volume in one second as a percent of the predicted value (FEV(1) % predicted), body mass index (BMI) and number of hospitalizations in the previous year. RESULTS: Forty-eight subjects completed the Life-Space Assessment. Subjects had a life-space score of 88 ± 26, FEV(1) % predicted of 66% ± 26% and BMI of 22.5 ± 3.3. There was a statistically significant negative linear correlation between the number of times a subject was hospitalized in the previous year and life-space mobility (P = 0.001, R(2) = 0.20). This association was independent of FEV(1) % predicted and BMI. CONCLUSION: The life-space mobility score is associated with frequency of hospitalization in adults with CF. A prospective study should be undertaken to assess the ability of the Life-Space Assessment to predict hospitalization and other outcomes in adults with CF.

Clinical, Molecular, and Genetic Characteristics of PAPA Syndrome: A Review.

PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) is an autosomal dominant, hereditary auto-inflammatory disease arising from mutations in the PSTPIP1/CD2BP1 gene on chromosome 15q. These mutations produce a hyper-phosphorylated PSTPIP1 protein and alter its participation in activation of the "inflammasome" involved in interleukin-1 (IL-1ß) production. Overproduction of IL-1ß is a clear molecular feature of PAPA syndrome. Ongoing research is implicating other biochemical pathways that may be relevant to the distinct pyogenic inflammation of the skin and joints characteristic of this disease. This review summarizes the recent and rapidly accumulating knowledge on these molecular aspects of PAPA syndrome and related disorders.