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Background: Little consensus is available regarding the standard treatment for recurrent anterior instability of the shoulder. Typically, treatment selection has been based on training and tradition rather than the available evidence. Purpose: This study aimed to compare the clinical outcomes between arthroscopic Bankart procedure and the Latarjet procedure in the treatment of recurrent anterior shoulder instability with emphasis on follow-up time. Study Design: Systematic review and meta-analysis. Methods: We searched PubMed, Cochrane Central Register of Controlled Trials, Scopus, Ovid, and Web of Science up to January 2018 and included studies that compared arthroscopic Bankart versus Latarjet for treatment of anterior shoulder instability. Continuous data, such as operative time and patient-reported outcomes, were pooled as mean differences (MDs), whereas dichotomous data, such as recurrence, revision, redislocation, arthropathy, infection, and hematoma, were pooled as risk ratios (RRs), with 95% CIs. Results: Pooling data from 7 cohort studies (3275 patients) showed that arthroscopic Bankart was associated with a higher risk of redislocation (RR, 2.74; 95% CI, 1.48-5.06; P = .03), a higher risk of recurrence (RR, 2.87; 95% CI, 1.91-4.30; P < .0001), and a lower risk of infection (RR, 0.16; 95% CI, 0.06-0.43; P = .0002) compared with Latarjet, while the effect size did not favor arthroscopic Bankart or Latarjet in terms of Rowe score (MD, 0.22; 95% CI, –5.64 to 6.08; P = .94), revision (RR, 0.34; 95% CI, 0.08-1.39; P = .13), and hematoma (RR, 0.20; 95% CI, 0.03-1.19; P = .07). The effect estimate showed a pronounced advantage for Latarjet from 6 to 10 years postoperatively in terms of recurrence and redislocation (RR, 3.00; 95% CI, 1.98-4.56 and RR, 2.85; 95% CI, 1.51-5.38, respectively). Conclusion: Our results showed that Latarjet had less risk of recurrence and redislocation with longer follow-up time. Both procedures were comparable in terms of Rowe score, the need for revision, and postoperative hematoma formation, whereas Bankart repair was associated with a lower risk of infection.

Background:Piperonyl butoxide (PBO) is a pesticide synergist used in residential, commercial, and agricultural settings. PBO was recently found to inhibit Sonic hedgehog (Shh) signaling, a key developmental regulatory pathway. Disruption of Shh signaling is linked to birth defects, including holoprosencephaly (HPE), a malformation of the forebrain and face thought to result from complex gene–environment interactions.Objectives:The impact of PBO on Shh signaling in vitro and forebrain and face development in vivo was examined.Methods:The influence of PBO on Shh pathway transduction was assayed in mouse and human cell lines. To examine its teratogenic potential, a single dose of PBO (22–1,800mg/kg) was administered by oral gavage to C57BL/6J mice at gestational day 7.75, targeting the critical period for HPE. Gene–environment interactions were investigated using Shh+/− mice, which model human HPE-associated genetic mutations.Results:PBO attenuated Shh signaling in vitro through a mechanism similar to that of the known teratogen cyclopamine. In utero PBO exposure caused characteristic HPE facial dysmorphology including dose-dependent midface hypoplasia and hypotelorism, with a lowest observable effect level of 67mg/kg. Median forebrain deficiency characteristic of HPE was observed in severely affected animals, whereas all effective doses disrupted development of Shh-dependent transient forebrain structures that generate cortical interneurons. Normally silent heterozygous Shh null mutations exacerbated PBO teratogenicity at all doses tested, including 33mg/kg.Discussion:These findings demonstrate that prenatal PBO exposure can cause overt forebrain and face malformations or neurodevelopmental disruptions with subtle or no craniofacial dysmorphology in mice. By targeting Shh signaling as a sensitive mechanism of action and examining gene–environment interactions, this study defined a lowest observable effect level for PBO developmental toxicity in mice more than 30-fold lower than previously recognized. Human exposure to PBO and its potential contribution to etiologically complex birth defects should be rigorously examined. https://doi.org/10.1289/EHP5260

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Osteosarcoma and chondrosarcoma are sarcomas of the bone and the cartilage that are primarily treated by surgical intervention combined with high toxicity chemotherapy. In search of alternative metabolic approaches to address the challenges in treating bone sarcomas, we assessed the growth dependence of these cancers on leucine, one of the branched-chain amino acids (BCAAs), and BCAA metabolism. Tumor biopsies from bone sarcoma patients revealed differential expression of BCAA metabolic enzymes. The cytosolic branched-chain aminotransferase (BCATc) that is commonly overexpressed in cancer cells, was down-regulated in chondrosarcoma (SW1353) in contrast with osteosarcoma (143B) cells that expressed both BCATc and its mitochondrial isoform BCATm. Treating SW1353 cells with gabapentin, a selective inhibitor of BCATc, further revealed that these cells failed to respond to gabapentin. Application of the structural analog of leucine, N-acetyl-leucine amide (NALA) to disrupt leucine uptake, indicated that all bone sarcoma cells used leucine to support their energy metabolism and biosynthetic demands. This was evident from the increased activity of the energy sensor AMP-activated protein kinase (AMPK), down-regulation of complex 1 of the mammalian target of rapamycin (mTORC1), and reduced cell viability in response to NALA. The observed changes were most profound in the 143B cells, which appeared highly dependent on cytosolic and mitochondrial BCAA metabolism. This study thus demonstrates that bone sarcomas rely on leucine and BCAA metabolism for energy and growth; however, the differential expression of BCAA enzymes and the presence of other carbon sources may dictate how efficiently these cancer cells take advantage of BCAA metabolism.