Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.

Dysregulation of the alternative pathway (AP) of the complement system is a significant contributor to age-related macular degeneration (AMD), a primary cause of irreversible vision loss worldwide. Here, we assess the contribution of the liver-produced complement factor H-related 4 protein (FHR-4) to AMD initiation and course of progression. We show that FHR-4 variation in plasma and at the primary location of AMD-associated pathology, the retinal pigment epithelium/Bruch's membrane/choroid interface, is entirely explained by three independent quantitative trait loci (QTL). Using two distinct cohorts composed of a combined 14,965 controls and 20,741 cases, we ascertain that independent QTLs for FHR-4 are distinct from variants causally associated with AMD, and that FHR-4 variation is not independently associated with disease. Additionally, FHR-4 does not appear to influence AMD progression course among patients with disease driven predominantly by AP dysregulation. Modulation of FHR-4 is therefore unlikely to be an effective therapeutic strategy for AMD.

The Effect of Implant Density on Adolescent Idiopathic Scoliosis Fusion: Results of the Minimize Implants Maximize Outcomes Randomized Clinical Trial.

BACKGROUND: Severe adolescent idiopathic scoliosis (AIS) can be treated with instrumented fusion, but the number of anchors needed for optimal correction is controversial. METHODS: We conducted a multicenter, randomized study that included patients undergoing spinal fusion for single thoracic curves between 45° and 65°, the most common form of operatively treated AIS. Of the 211 patients randomized, 108 were assigned to a high-density screw pattern and 103, to a low-density screw pattern. Surgeons were instructed to use ≥1.8 implants per spinal level fused for patients in the high-implant-density group or ≤1.4 implants per spinal level fused for patients in the low-implant-density group. The primary outcome measure was the percent correction of the coronal curve at the 2-year follow-up. The power analysis for this trial required 174 patients to show equivalence, defined as a 95% confidence interval (CI) within a ±10% correction margin with a probability of 90%. RESULTS: In the intention-to-treat analysis, the mean percent correction of the coronal curve was equivalent between the high-density and low-density groups at the 2-year follow-up (67.6% versus 65.7%; difference, -1.9% [95% CI: -6.1%, 2.2%]). In the per-protocol cohorts, the mean percent correction of the coronal curve was also equivalent between the 2 groups at the 2-year follow-up (65.0% versus 66.1%; difference, 1.1% [95% CI: -3.0%, 5.2%]). A total of 6 patients in the low-density group and 5 patients in the high-density group required reoperation (p = 1.0). CONCLUSIONS: In the setting of spinal fusion for primary thoracic AIS curves between 45° and 65°, the percent coronal curve correction obtained with use of a low-implant-density construct and that obtained with use of a high-implant-density construct were equivalent. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Predicting Satisfaction of Parents of Pediatric Patients: Perceived Quality of Providers' Communication Mitigates Negative Effects of Shorter than Desired Consultations.

This research investigated the predictors of satisfaction for parents of pediatric patients after a clinical consultation. Specifically, we assessed whether perceptions of their provider's communication quality influenced the degree to which their (dis)satisfaction with consultation length associated with their provider rating and intent to recommend the provider's office. Using patient satisfaction survey data collected after initial clinical visits to a pediatric hospital (N = 12,004), we found that communication quality was a stronger predictor for those who were dissatisfied with their consultation length, whereas communication quality made a relatively smaller difference for those who were satisfied with their consultation length. Put another way, parents' dissatisfaction with their child's consultation length mattered little when they perceived their provider to be high in communication quality, but it reduced their ratings and intentions to recommend when they perceived their provider to be low in communication quality. These results suggest that providers' communication behaviors have the capacity to buffer patients' negative evaluations otherwise incurred from shorter than desired consultations.

Rumen effects of monensin in dry cow diets varying in energy density.

Controversy has existed as to whether monensin will provide equal or differential benefits in a higher-energy, lower-roughage close-up diet versus a higher-roughage, lower-energy diet. Our objective was to determine the rumen effects of a controlled-energy, high-fiber diet balanced to meet but not greatly exceed energy requirements during the dry period or a traditional 2-group approach of higher-energy close-up diet. The effects of added monensin in each diet type were determined. Multiparous Holstein cows (n = 17) were fitted surgically with ruminal cannulas. During the first 4 wk of the dry period, all cows were fed a controlled-energy, high-fiber diet (CE) as a total mixed ration for ad libitum intake. During the last 3 wk before calving, half of the cows were switched to a higher-energy, close-up diet until calving (CU), whereas the other half continued to receive the CE diet. Within each dietary group, half of the cows received monensin (MON) supplementation in the diet (24.2 g/t of total dry matter) and half did not (CON). After calving, all cows received the same lactation diet containing monensin (15.4 g/t of dietary dry matter). At 14 d prepartum, dry matter intake was not different across treatments. The weight of rumen contents was greater for cows fed CE. Rumen liquid dilution rate, solids passage rate, pH, total volatile fatty acid (VFA) concentrations, molar proportions of acetate and propionate, and papillae length did not differ among diets. Butyrate percentage tended to be greater for cows fed CE. Postpartum, dry matter intake, mass of rumen contents, solids passage rate, pH, total VFA concentration, molar percentages of propionate and butyrate, and papillae length did not differ among treatments. Liquid dilution rate (16.6, 10.7, 16.0, and 18.2%/h for CE + CON, CE + MON, CU + CON, and CU + MON, respectively) was affected by a diet × monensin interaction. Cows on the CE + CON diet had a greater ruminal proportion of acetate than did cows fed CU + CON, whereas cows fed monensin on either diet were intermediate (diet × monensin interaction). Addition of MON to the CU diet decreased the proportion of propionate (diet × monensin interaction). Cows fed CE had greater mass of rumen contents before parturtition but the high inclusion of wheat straw in the CE diet did not negatively affect rumen papillae length. Monensin inclusion differentially affected liquid passage rate and VFA concentrations.

Narrative Review of the objective analysis of long-term outcome of the Ponseti technique: experience from Dallas.

In 2001, Texas Scottish Rite Hospital for Children (TSRH) prospectively began a clubfoot database that included all of our patients with clubfeet who were willing to enroll. Nonoperative treatment, primarily the Ponseti method, was utilized. This article summarizes the experience from Dallas treating idiopathic clubfeet using the Ponseti technique, and is based on previously published studies utilizing information from the database. Patient clinical outcomes were defined as "good" (plantigrade foot achieved either with or without a percutaneous heel-cord tenotomy), "fair" (a plantigrade foot that required a limited procedure, such as tibialis anterior tendon transfer or posterior release), or "poor" (a plantigrade foot that required posteromedial release). Nearly 95% of idiopathic clubfeet obtained initial correction using the Ponseti technique, but relapses occurred and by age two years 24% needed some surgical intervention, usually limited procedures. Use of Dimeglio's rating system before treatment strongly correlated with the probability of a "good" outcome at two years. Objective measurements of brace wear compliance (iButton) in those who reached age two years with "good" outcomes demonstrated an unexpected pattern of diminishing use of the foot abduction orthoses over the first two years of brace wear. By the 18-month period of brace wear, 1/3 patients wore the orthoses less than 6 hours per day, and nearly half of the patients wore the orthoses less than 8 hours per day. Between ages 2-5 years, nearly 21% of the corrected clubfeet at age two years needed limited procedures to maintain/regain plantigrade positioning. Lateral weight-bearing radiographs between 18-24 months were not helpful in predicting future relapse in these patients, and are no longer routinely obtained. Following these patients for normal development is important, as nearly 9% of infants initially presenting as idiopathic clubfeet were eventually found to have another disorder including neurological, syndromic, chromosomal, or spinal abnormalities. We continue to emphasize the need to devote great attention to detail when using the Ponseti method in an effort to optimize the clinical outcomes.

99mTc-labelled glucosamine in the assessment of systemic sclerosis inflammatory lung disease: a novel inexpensive investigative tool with predictive value.

OBJECTIVE: To evaluate the role of 99mTc-labelled glucosamine [99mTc-ECDG] as a clinical biomarker for the early detection of interstitial lung disease (ILD) in systemic sclerosis (SSc). METHODS: In this prospective pilot study, glucosamine scanning (GS) was performed in 15 SSc patients, with and without ILD. Collected data included patient disease characteristics, autoantibody profile, GS results, high-resolution computerised tomography [HRCT], pulmonary function tests [PFT], and transthoracic echocardiogram [TTE]. Glucosamine results were correlated with patient clinical profile, HRCT, and PFT's findings. RESULTS: Lung uptake of 99mTc-ECDG was high in 4 patients, moderate in 3, mild in 5, and normal in 3 with SSc, respectively. Of the patients with high and moderate uptake there was a 100% correlation between 99mTc-ECDG uptake and HRCT showing ILD. Of the 5 patients with mild 99mTc-ECDG uptake, 4 patients had aspiration pneumonia, and 1 had early ILD using HRCT. Of the 3 patients with normal 99mTc-ECDG, 2 had normal HRCTs; the third had severe pulmonary arterial hypertension with minimal HRCT changes of ILD. High and moderate 99mTc-ECDG lung uptake predicted abnormal PFT's in 100% of cases. In 3 patients, there was less extensive disease depicted on the 99mTc-ECDG scans than on the HRCT. These patients demonstrated a more favourable outcome than would have been expected from the HRCT scans alone. Mild 99mTc-ECDG lung uptake correlated with abnormal PFT's in 60% of cases. The pattern of 99mTc-ECDG uptake was excellent (100%) at distinguishing metabolically active ILD from aspiration pneumonia. Diffuse uptake was noted in the former and patchy uptake in the latter disease entity. CONCLUSION: Increased 99mTc-ECDG uptake in scleroderma lung correlated positively with both structural and functional changes. 99mTc-ECDG is a useful adjunct helping elucidate inflammation secondary to aspiration pneumonia and/or other causes of abnormal PFT's.

Genetic association and characterization of FSTL5 in isolated clubfoot.

Talipes equinovarus (clubfoot, TEV) is a congenital rotational foot deformity occurring in 1 per 1000 births with increased prevalence in males compared with females. The genetic etiology of isolated clubfoot (iTEV) remains unclear. Using a genome-wide association study, we identified a locus within FSTL5, encoding follistatin-like 5, significantly associated with iTEV. FSTL5 is an uncharacterized gene whose potential role in embryonic and postnatal development was previously unstudied. Utilizing multiple model systems, we found that Fstl5 was expressed during later stages of embryonic hindlimb development, and, in mice, expression was restricted to the condensing cartilage anlage destined to form the limb skeleton. In the postnatal growth plate, Fstl5 was specifically expressed in prehypertrophic chondrocytes. As Fstl5 knockout rats displayed no gross malformations, we engineered a conditional transgenic mouse line (Fstl5LSL) to overexpress Fstl5 in skeletal osteochondroprogenitors. We observed that hindlimbs were slightly shorter and that bone mineral density was reduced in adult male, but not female, Prrx1-cre;Fstl5LSL mice compared with control. No overt clubfoot-like deformity was observed in Prrx1-cre;Fstl5LSL mice, suggesting FSTL5 may function in other cell types to contribute to iTEV pathogenesis. Interrogating published mouse embryonic single-cell expression data showed that Fstl5 was expressed in cell lineage subclusters whose transcriptomes were associated with neural system development. Moreover, our results suggest that lineage-specific expression of the Fstl genes correlates with their divergent roles as modulators of transforming growth factor beta and bone morphogenetic protein signaling. Results from this study associate FSTL5 with iTEV and suggest a potential sexually dimorphic role for Fstl5 in vivo.

Spinal balance and lumbar curve stability after selective thoracic fusion in idiopathic scoliosis.

PURPOSE: Selective thoracic fusion (STF) for double curve patterns in idiopathic scoliosis is an attractive treatment option. However, short-term coronal decompensation and truncal imbalance are known findings. Previous studies with hook constructs showed that eventually balance is achieved via an increase in lumbar curve magnitude, as the lumbosacral obliquity did not change following surgery. Our aim is to investigate patients with idiopathic curves who underwent STF using all-pedicle screw constructs to determine if the uninstrumented lumbar curve and lumbosacral obliquity responded in the same manner as was previously reported with all-hook constructs. METHODS: 102 consecutive patients with Lenke 1B, 1C or 3C curves who underwent STF using all-screw constructs at a single institution were included in this study. Radiographic assessment was performed, and patient reported outcomes were obtained. Subgroup analyses were performed based on preoperative thoracic: lumbar curve ratio as well as lumbar curve magnitude. RESULTS: Overall, the patients showed statistically significant improvement in both trunk shift and L4-pelvis obliquity at final follow-up. The uninstrumented lumbar curves trended toward improvement over time, but did not reach statistical significance (p = 0.107). SRS-30 scores were statistically significantly improved in multiple domains. CONCLUSION: Selective thoracic fusion is an excellent treatment option in most double curve patterns. Balance in the coronal plane is predictably achieved at 2-year follow-up. The lumbosacral obliquity improves more with screw technology than was previously found with hook constructs; therefore, the improvement in balance over time does not depend upon an increase in the uninstrumented lumbar curve. LEVEL OF EVIDENCE: IV.

Are Some Randomized Clinical Trials Impossible?

Congenital tibial pseudarthrosis is a rare condition seen in neurofibromatosis type 1 (NF1), and treatment is complex. A randomized, placebo-controlled trial of bone morphogenetic protein (rhBMP-2; INFUSE bone graft) at time of tibial surgery was developed by the Neurofibromatosis Clinical Trials Consortium. Patients were randomized to receive rhBMP-2 that would, or would not, be added to the standard surgical procedure consisting of resection of pseudarthrosis tissue, insertion of a rigid intramedullary rod, and placement of autogenous iliac crest bone graft. Despite involvement of 16 centers with wide experience with NF1 orthopaedic management, only 5 patients (of 54 required) were able to be enrolled in the study during a 3-year time period. Because of the inability to recruit sufficient patients, this study was closed in June 2019, with plans to terminate. The obstacles that were encountered during the study are summarized. The authors question whether a randomized, placebo-controlled trial of a rare pediatric orthopaedic condition is possible to accomplish. Recommendations are provided to guide future studies of orthopaedic manifestations of NF1.Level of Evidence: Level V.

Effects of prepartum diets varying in dietary energy density and monensin on early-lactation performance in dairy cows.

Our objectives were to evaluate the effects of prepartum monensin supplementation and dry-period nutritional strategy on the postpartum productive performance of cows fed monensin during lactation. A total of 102 Holstein cows were enrolled in the experiment (32 primiparous and 70 multiparous). The study was a completely randomized design, with randomization restricted to balance for parity, body condition score, and expected calving date. A 2 × 2 factorial arrangement of prepartum treatments was used; the variables of interest were prepartum feeding strategy [controlled-energy diet throughout the dry period (CE) vs. controlled-energy diet from dry-off to 22 d before expected parturition, followed by a moderate-energy close-up diet from d 21 before expected parturition through parturition (CU)] and prepartum monensin supplementation [0 g/t (control, CON) or 24.2 g/t (MON); Rumensin; Elanco Animal Health, Greenfield, IN]. Lactation diets before and after the dry period contained monensin at 15.4 g/t. During the close-up period, cows fed CU had greater DM and NEL intakes than cows fed CE. Calf BW at birth tended to be greater for cows fed CU than for those fed CE but was not affected by MON supplementation. Diet did not affect calving difficulty score, but cows supplemented with MON had an increased calving difficulty score. We found a tendency for a MON × parity interaction for colostral IgG concentration, such that multiparous MON cows tended to have lower IgG concentration than CON cows, but colostral IgG concentration for primiparous MON and CON cows did not differ. Postpartum milk yield did not differ between diets but tended to be greater for cows supplemented with MON. Milk fat and lactose content were greater for cows fed CU than for those fed CE, and lactose content and yield were increased for cows supplemented with MON. Solids-corrected and fat-corrected milk yields were increased by MON supplementation, but were not affected by diet. Overall means for postpartum DMI did not differ by diet or MON supplementation. The CU diet decreased the concentration of nonesterified fatty acids during the close-up period but increased it postpartum. Neither diet nor monensin affected ß-hydroxybutyrate or liver composition. Overall, postpartum productive performance differed little between prepartum dietary strategies, but cows fed MON had greater energy-corrected milk production. In herds fed monensin during lactation, monensin should also be fed during the dry period.

Comparison of prepartum low-energy or high-energy diets with a 2-diet far-off and close-up strategy for multiparous and primiparous cows.

Previous research demonstrated that nutrition during the far-off (early) dry period may be as important to transition success as nutrition during the close-up dry period. Our objectives were to determine if a low-energy, high-fiber diet fed throughout the dry period improved metabolic status and production of dairy cows compared with a higher-energy diet or a 2-diet system, and to compare responses of cows and heifers to those diets. Holstein cows (n = 25 with 10 primiparous per treatment) were assigned to each of 3 diets at 60 d before expected calving. Treatment LO [40.5% wheat straw; 5.6 MJ of net energy for lactation (NEL)/kg of DM] was designed to meet but not exceed National Research Council recommendations for ad libitum intake from dry-off until calving. Treatment HI was a high-energy diet (6.7 MJ of NEL/kg of DM) fed for ad libitum intake from dry-off until calving. For the LO+HI treatment, the LO diet was fed ad libitum from dry-off until 21 d before expected calving, followed by the HI diet until parturition. After parturition all cows were fed a lactation diet (7.0 MJ of NEL/kg of DM) through 63 d postpartum. Dry matter intake and body weight were greater for HI cows prepartum, but not postpartum. When LO+HI cows were switched to the HI diet, their dry matter intake increased to match that of HI cows. Cows fed HI had greater gain of body condition before calving but lost more postpartum. Energy balance postpartum was higher for LO cows than for HI cows. Milk production, protein content, and protein yield did not differ among diets. Milk fat content and yield were highest for HI cows, lowest for LO, and intermediate for LO+HI cows. The HI cows had lower serum nonesterified fatty acids prepartum than either LO or LO+HI, but greater concentrations postpartum. Serum ß-hydroxybutyrate did not differ prepartum, but was greater for HI than for LO or LO+HI postpartum. Serum glucose and insulin were lower for LO than HI and LO+HI prepartum; insulin was lower for LO and HI than for LO+HI postpartum. The LO cows had lower liver total lipid concentration postpartum than the HI cows and LO+HI cows. Primiparous cows generally responded to diets the same as multiparous cows. The LO+HI feeding strategy provided no benefit over the LO diet. Moreover, the high-energy diet, even when fed for only 19 d before calving in the LO+HI group, resulted in increased serum ß-hydroxybutyrate and liver total lipid concentrations compared with LO.

Successful Ponseti-treated Clubfeet at Age 2 Years: What Is the Rate of Surgical Intervention After This?

BACKGROUND: In recent decades, nonoperative Ponseti casting has become the standard of care in the treatment of idiopathic clubfoot. However, the rate of recurrence, even after successful Ponseti treatment is not insignificant. The purpose of this study was to determine the future rate, timing, and type of surgery needed in patients whose idiopathic clubfeet treated by Ponseti casting were considered successful at the age of 2 years. METHODS: Inclusion criteria for this retrospective study were patients under 3 months with idiopathic clubfoot treated exclusively by Ponseti casting, who had successful outcomes at 2 years of age without surgery, and who had at least 5 years of follow-up. The total number of surgical interventions in the age range 2 to 5 and above 5 years, the number and type of procedures performed, and the timing of surgery were reviewed. RESULTS: Three hundred thirty-six patients with a total of 504 clubfeet fulfilled the inclusion criteria. One hundred twenty-two of these 336 patients (36.3%) eventually underwent surgical intervention. Between 2 and 5 years of age, 79 patients (23.5%) with 104 feet (20.6%) underwent surgery. The most common procedures performed between 2 and 5 years were limited (a la carte) in scope: tibialis anterior tendon transfer, posterior release, plantar fascia release, and repeat tendo-Achilles lengthening. At age above 5 years, 53 patients (20.1%) with 65 feet (16.9%) underwent surgery. Ten of these 53 patients had already undergone surgery between 2 and 5 years of age. The procedures most commonly performed were similar. CONCLUSIONS: In patients with idiopathic clubfoot who reached 2 years of age with successful outcomes from Ponseti cast treatment, ∼35% eventually underwent surgical intervention, mostly limited (a la carte), to regain or maintain a plantigrade foot. The most commonly performed procedures include tibialis anterior tendon transfer, posterior capsular release, plantar fascia release and repeat tendo-Achilles lengthening, either in isolation or in combination. However, before considering surgery, the need for these procedures can, and should, be minimized by recasting recurrent deformities using Ponseti method. LEVEL OF EVIDENCE: Level III.

Objective Measurement of Brace Wear in Successfully Ponseti-Treated Clubfeet: Pattern of Decreasing Use in the First 2 Years.

PURPOSE: Once Ponseti correction of a clubfoot is achieved and 3-month full-time bracing treatment is completed, part-time bracing treatment for 12 hours at night for 2 to 4 years is considered necessary to maintain a successful outcome. This study objectively documents the amount of daily orthosis wear time in those who maintained correction at age 2 years and, in so doing, determines how well patients' caretakers comply with the prescribed brace program. METHODS: Patients <3 months old with idiopathic clubfeet when Ponseti treatment was initiated, who successfully maintained correction at age 2 years without surgery and who had complete objective brace wear data, were included. The foot abduction orthoses had a temperature data logger embedded in a shoe. Six 3-month time intervals were monitored in every patient as follows: full time: 0 to 3; night time: 4 to 6, 7 to 9, 10 to 12, 13 to 15, and 16 to 18 months. The families were not informed that hours of brace wear were being measured. RESULTS: One hundred twenty-four patients with 187 clubfeet were included. During the 0- to 3-month interval, wear time averaged 19.8 hr/d. After this period of full-time use, the night-time brace wear decreased over each of the subsequent five intervals: 11.9, 9.6, 8.6, 7.9, and 7.7 hours. By the 18-month period of brace wear, 1 of 3 patients wore the orthoses less than 6 hours per day, and nearly 1 of 2 patients wore the orthoses less than 8 hours per day. DISCUSSION: In patients evaluated at age 2 years whose clubfeet had successful nonsurgical treatment, night-time brace wear varied greatly and decreased over each 3-month period measured. By the second year of bracing treatment, nearly half of the patients wore them 8 hours or less. LEVEL OF EVIDENCE: Level IV case series.

Evaluating unmet needs in patients undergoing surgery for colorectal cancer: a patient reported outcome measures study.

AIM: Patient reported outcome measures (PROMs) are self-reported measures of patients' health status or health-related quality of life at a single point in time. We aimed to evaluate the use of a colorectal PROM and conducted a focus group to further explore this and other unmet needs in our patient population treated surgically for colorectal cancer. METHOD: A multidisciplinary research group consisting of colorectal surgeons, nurse specialists, psychologists, sociologists and patient representatives devised a composite tool of new and existing outcome measures which was piloted in our local population (n = 35). Participants were subsequently invited to attend a semi-structured focus group during which the PROM was reviewed and an unmet needs analysis was performed. Thematic analysis of focus group transcripts was undertaken for emergent themes. RESULTS: Initial consensus was for a tool including the EQ-5D, Functional Assessment of Cancer Therapy - Colorectal (FACT-C), the distress thermometer, a validated measure of stigma, an unmet needs analysis, and questions assessing the psychological impact of cancer. Median and interquartile range values suggested that all metrics were discriminatory with the exception of FACT-C. All participants agreed that the tool was acceptable and reflected the current state of their health and emotions. Thematic analysis of focus group transcripts identified four major themes: physical symptoms, emotional response, information provision and coping mechanisms. CONCLUSION: Through expert consensus, local piloting and patient focus groups we have evaluated a novel PROM for colorectal cancer. Furthermore, through our direct engagement with patients we have identified several unmet needs which we are currently exploring within the clinical service.

Clubfoot Infants Initially Thought to be Idiopathic, But Later Found Not to Be. How do They do With Nonoperative Treatment?

BACKGROUND: Infants thought to be normal with idiopathic clubfeet when nonoperative treatment begins may later be found to have other complicating diagnoses. The purpose of this study was to determine the incidence of this occurrence, and to compare the clinical outcomes of these "nonidiopathic" patients with idiopathic clubfoot patients. METHODS: Infants below 3 months old with clubfeet who were thought to be normal (idiopathic) at presentation and had ≥2-year follow-up were studied. Treatment consisted of either the Ponseti method or the French physical therapy method. In total, 789 patients with 1174 clubfeet were identified. Those who were idiopathic (group 1) were compared with those later found to be nonidiopathic (group 2). The outcomes at 2 years were assessed as good (plantigrade foot±heelcord tenotomy only), fair (limited procedures), or poor (full-posteromedial release). For those feet rated good at age 2 years, outcomes were again assessed age 5 years and above. RESULTS: In total, 70 patients (8.9%) of the 789 enrolled patients were eventually found to have another disorder including neurological, syndromic, chromosomal, or spinal abnormalities. The remaining 719 idiopathic patients with 1062 clubfeet (group 1) were compared with these 70 nonidiopathic patients with 112 clubfeet (group 2). At age 2 years, in group 1 81% of the feet were rated good, 11% fair, and 8% poor, whereas in group 2 70% of the feet were rated good, 11% fair, and 19% poor (P=0.0004).With follow-up exceeding age 5 years in those rated good at age 2 years: in group 1, 73% continued to do well, but 22% rated fair, and 5% poor. In group 2, 59% continued to do well, but 31% rated fair, and 10% poor (P=0.046). CONCLUSIONS: For infants with clubfeet who were initially thought to be idiopathic, nearly 9% were later found to have a complicating disorder. Despite this, these patients' clubfeet can be expected to respond favorably to nonoperative treatment. However, they will require more surgical intervention early (by age 2 years) and later (age, 5 years and above) when compared with normal infants with idiopathic clubfeet. LEVEL OF EVIDENCE: Level IV-therapeutic, case series.

Repeat Surgical Interventions Following "Definitive" Instrumentation and Fusion for Idiopathic Scoliosis: 25-Year Update.

STUDY DESIGN: Single-institution, retrospective review of prospectively collected data on pediatric patients with adolescent idiopathic scoliosis (AIS) undergoing spinal fusion with a minimum two-year follow-up. OBJECTIVE: To determine the rate of reoperation in AIS patients undergoing spine fusion from 2008 to 2012. SUMMARY OF BACKGROUND DATA: Recent trends in the surgical treatment of AIS have included increased use of all-pedicle screw constructs, smaller implants, more posterior-only approaches, and improved correction techniques. METHODS: A retrospective review of 467 patients undergoing spinal fusion from 2008 to 2012 was performed. Demographic, clinical, radiographic, and surgical data were collected prospectively on all patients for the index procedure and any reoperations. Data were compared to previously published cohorts of patients from the authors' institution who underwent spinal fusion for AIS between 1988 and 2007. RESULTS: The rate of reoperation in this five-year cohort of patients was 9.9%. The most common indications for reoperation were infection (4.5%: 2.4% delayed infections and 2.1% acute infections), symptomatic implants (2.1%), and misplaced pedicle screws (1.7%). When compared to the 2003-2007 cohort, the rate of reoperation for acute infection and malpositioned pedicle screws increased significantly (p = .01 and p = .04), whereas the rate of reoperation for curve progression decreased (p = .01). Reoperations for acute infections and malpositioned pedicle screws also increased significantly (p = .047 and p = .042) compared with the 1988-2002 cohort, whereas the rate of reoperation for pseudarthrosis decreased (p = .002). CONCLUSION: Reoperation rates for AIS have not improved with more sophisticated implants and techniques, predominantly because of increased acute infections and malpositioned pedicle screws despite decreasing pseudarthrosis rates and curve progression. LEVEL OF EVIDENCE: Level II.

The Lumbar Gap Measurement in Lenke 1-4C Curves.

STUDY DESIGN: Retrospective review. OBJECTIVES: To assess whether the lumbar gap (LG) measurement, which is the distance between the center sacral vertical line and the concave edge of the apical vertebra of the lumbar curve, would be a useful tool to predict the need for lumbar curve fusion in the Lenke 1-4C curves. SUMMARY OF BACKGROUND DATA: The current treatment guidelines of selective thoracic fusion in the Lenke 1-4C curves are not routinely accepted. METHODS: One hundred three adolescent idiopathic scoliosis (AIS) patients had undergone either selective thoracic fusion (STF) or both thoracic and lumbar curves fusion (TLF) for Lenke 1-4C curves. The correlations between the fusion decision making and preoperative LG, coronal balance, thoracic and lumbar Cobb, apical vertebra translation, and rotation were analyzed. The radiographic outcomes and SRS-30 of a minimum 2-year follow-up were reviewed in each group. RESULTS: A total of 51 patients (49.5%) underwent an STF, and 52 patients (50.5%) underwent a TLF. The mean LG was 22.0 ± 8.8 mm in the TLF, which was 2.3 times greater than the STF (9.6 ± 3.9 mm) (p < .0001). Only 5% of the lumbar curves were fused when the LG was 10 mm or less. Ninety percent of the lumbar curves were fused when the LG was 16 mm or greater, and 100% lumbar curves were fused with an LG of 21 mm or greater. The preoperative coronal imbalance to the left in the TLF was significantly greater than the STF. A mean 47% thoracic correction corresponded to a mean 39% spontaneous correction of the lumbar curve obtained in the SFT, which was significantly different from the TLF (56% and 65%). There were no differences in the SRS-30 scores at 2 years postoperatively between the STF and the TLF. CONCLUSION: The lumbar curve should not be fused when the LG was 10 mm or less, and very likely should be fused when the LG exceeds 20 mm in the Lenke 1-4C AIS patients. LEVEL OF EVIDENCE: Level III.

Enhancing the photoluminescence of surface anchored metal-organic frameworks: mixed linkers and efficient acceptors.

We present two approaches to enhance the photoluminescence quantum yield (PLQY) of surface-anchored metal-organic frameworks (SURMOFs). In the first approach we fabricate SURMOFs from a mix of an emissive linker with an optically-inert linker of equivalent length, diluting the emissive linker while maintaining the SURMOF structure. This approach enhances the internal PLQY. However, the increase in internal PLQY is achieved at the expense of a drastic reduction in optical absorption, thus the external PLQY remains low. To overcome this limitation, a second approach is explored wherein energy-accepting guest chromophores are infiltrated into the framework of the active linker. At the correct acceptor concentration, an internal PLQY of 52% - three times higher than the previous approach - is achieved. Additionally, the absorption remains strong leading to an external PLQY of 8%, an order of magnitude better than the previous approach. Using this strategy, we demonstrate that SURMOFs can achieve PLQYs similar to their precursor chromophores in solution. This is of relevance to SURMOFs as emitter layers in general, and we examine the optimized emitter layer as part of a photon upconversion (UC) SURMOF heterostructure. Surprisingly, the same PLQY is not observed after triplet-triplet annihilation in the UC heterostructure as after its normal photoexcitation (although the UC layers exhibit low thresholds consistent with those reported in our previous work). We discuss the potential bottlenecks in energy transport that could lead to this unexpected reduction in PLQY after excitation via triplet-triplet annihilation, and how future design of SURMOF UC multilayers could overcome these limitations.

rhBMP-2 and Intramedullary Fixation in Congenital Pseudarthrosis of the Tibia.

BACKGROUND: In congenital pseudarthrosis of the tibia, use of intramedullary (IM) fixation and autogenous bone graft has long been the standard of care. This study was undertaken to determine whether the addition of rhBMP-2 to this treatment method further enhances healing potential. METHODS: Twenty-one patients with congenital pseudarthrosis of the tibia were evaluated. Fifteen of these patients had neurofibromatosis type 1 (NF1). All had IM fixation and autogenous bone graft, followed by a BMP-soaked collagen sponge wrapped around both the fracture site and bone graft. A minimum 2 years' follow-up was required. RESULTS: Follow-up averaged 7.2 years (range, 2.1 to 12.8 y). Sixteen of 21 tibias achieved bone union following the index surgery, at an average 6.6 months postoperatively. The 5 persistent nonunions occurred in NF1 patients. Further surgery was undertaken in these 5 NF1 patients, including the use of BMP. One of the 5 healed, 1 had persistent nonunion, and 3 eventually had amputation. Of the 16 patients who healed initially following the index surgery, 5 refractured (3 had NF1). Of these 5 patients, the IM fixation at the index surgery did not cross the ankle joint, and refracture occurred at the rod tip in 4. Three of these 5 patients healed following further surgery, 1 had persistent nonunion, and 1 had amputation. All of those with eventual amputation had NF1. No deleterious effects related to the use of BMP-2 were recognized in any patient. CONCLUSIONS: The addition of rhBMP-2 appears to be helpful in shortening the time required to achieve fracture union in those who healed, but its use does not insure that healing will occur. LEVEL OF EVIDENCE: Level IV-therapeutic, case series.

Infiltrated photonic crystals for light-trapping in CuInSe2 nanocrystal-based solar cells.

Solution processable nanocrystal solar cells combine the advantages of low-cost printing and wide range of accessible absorber materials, however high trap densities limit performance and layer thickness. In this work we develop a versatile route to realize the infiltration of a photonic crystal, with copper indium diselenide nanocrystal ink. The photonic crystal allows to couple incident light into pseudo-guided modes and thereby enhanced light absorption. For the presented design, we are able to identify individual guided modes, explain the underlying physics, and obtain a perfect match between the measured and simulated absorption peaks. For our relatively low refractive index layers, a 7% maximum integrated absorption enhancement is demonstrated.