Comparison of a Cryopneumatic Compression Device and Ice Packs for Cryotherapy Following Anterior Cruciate Ligament Reconstruction.

Background: The purpose of the current study was to evaluate and compare the effectiveness of a cryopneumatic compression device with that of standard ice packs following arthroscopic anterior cruciate ligament (ACL) reconstruction, with a primary focus on early postoperative pain. Methods: Participants were divided into two groups: cryopneumatic compression device group (CC group) and standard ice pack group (IP group). Patients in the CC Group (28 patients) received a cryopneumatic compression device (CTC-7, Daesung Maref) treatment, while patients in the IP group (28 patients) received standard ice pack cryotherapy postoperatively. All cryotherapy was applied three times (every 8 hours) per day for 20 minutes until discharge (postoperative day 7). Pain scores were assessed preoperatively and at 4, 7, and 14 days after surgery, and the primary outcome for analysis was pain at postoperative day 4 assessed using a visual analog scale (VAS). Other variables were opioid and rescue medication use, knee and thigh circumferences, postoperative drainage, and joint effusion quantified by a three-dimensional magnetic resonance imaging (MRI) reconstruction model. Results: The mean pain VAS score and difference in VAS relative to the preoperative measurements for postoperative day 4 were significantly lower in the CC group than in the IP group (p = 0.001 and p = 0.007, respectively). The sum of postoperative drainage and effusion quantified by MRI showed a significant reduction of postoperative effusion in the CC group compared to the IP group (p = 0.015). The average total rescue medication consumption was comparable between the two groups. Circumferential measurements at days 7 and 14 postoperatively relative to those at day 4 (index day) demonstrated no significant differences between the groups. Conclusions: Compared to standard ice packs, application of cryopneumatic compression was associated with a significant reduction in VAS pain scores and joint effusion during the early postoperative period following ACL reconstruction.

Surgical Trends of Shoulder Arthroplasty: Nationwide Epidemiologic Study in South Korea.

Background: The aim of this study was to determine the nationwide shoulder arthroplasty trends in South Korea based on an analysis of nationwide data acquired from the Korean Health Insurance Review and Assessment Service (HIRA). Methods: We analyzed a nationwide database acquired from the HIRA that covered 2008 to 2017. International Classification of Diseases, 10th Revision (ICD-10) codes and procedure codes were used to identify patients who underwent shoulder arthroplasty, including total shoulder arthroplasty (TSA), hemiarthroplasty (HA), and revision shoulder arthroplasty. Results: From 2008 to 2017, a total of 19,831 shoulder arthroplasties were performed; there were 16,162 TSAs and 3,669 hemiarthroplasties. During the 10-year study period, there was an exponential increase in the incidence of TSA (from 513 cases in 2008 to 3,583 cases in 2017), while the number of hemiarthroplasties remained steady. The most common diagnoses for TSA were rotator cuff tears (6,304 cases, 39.0%) and osteoarthritis (6,589 cases, 40.8%) for all 9 years. Osteoarthritis was the most common reason for TSA during the first 3 years (2008-2010), but rotator cuff tears ultimately surpassed osteoarthritis during the last 3 years (2015-2017). HA was performed to treat proximal humerus fracture (1,770 cases, 48.2%) and osteoarthritis (774 cases, 21.1%). In terms of hospital types, the rate of TSA in hospitals with 30-100 inpatient beds increased from 21.83% to 46.27%, while the rates of the other types of surgery decreased. A total of 430 revision surgeries were performed during the study period, and infection (152 cases, 35.3%) was the most common reason for revision surgery. Conclusions: Overall, the total count and incidence of TSA, unlike HA, increased rapidly between 2008 and 2017 in South Korea. Moreover, at the end of the study period, nearly half of the TSAs were performed in small hospitals (30 to 100 beds). Rotator cuff tears were the leading cause of TSA at the end of the study period. These findings revealed an explosive increase in reverse TSA surgery.

Outcomes of the use of cement-augmented cannulated pedicle screws in lumbar spinal fusion.

BACKGROUND CONTEXT: There are few studies of the radio-clinical outcomes of cement-augmented cannulated pedicle screw (CPS) fixation in osteoporotic patients. PURPOSE: To compare the radiological and clinical outcomes between groups receiving cement-augmented CPS and solid pedicle screws (SPS) in lumbar fusion surgery. STUDY DESIGN/SETTING: Retrospective comparative study PATIENT SAMPLE: A total of 187 patients who underwent lumbar fusion surgery for degenerative spinal stenosis or spondylolisthesis from 2014 to 2019. OUTCOME MEASURES: Radiological evaluation included screw failure, cage failure, rod breakage, and fusion grade at postoperative 6 months and 1 year. Pre- and postoperative visual analog scales for back pain (VAS-BP), leg pain (VAS-LP), Korean Oswestry disability index (K-ODI), and postoperative complications were also compared. METHODS: Outcomes of patients with high risk factors for implant failure [old age, osteoporosis, autoimmune disease or chronic kidney disease (CKD)] who underwent open transforaminal lumbar interbody fusion with cement-augmented CPS fixation (Group C, n=55) or SPS fixation (Group S, n=132) were compared. RESULTS: 324 pedicle screws in Group C and 775 pedicle screws in Group S were analyzed. Group C had a significantly higher average age and lower T-score, and included more patients with autoimmune disease and CKD than group S (all p<.05). Clear zones, screw migration and loss of correction were significantly less frequent in Group C (all p<.05). Thirteen screw breakages were observed; they were only in Group C (4.0%) and all were in the proximal of the two holes. Interbody and posterolateral fusion rates were not significantly different. At last follow-up, all clinical parameters including VAS-BP, VAS-LP, and K-ODI scores had improved significantly in both groups. Postoperative complications were not significantly different in the two groups. CONCLUSION: In lumbar fusion surgery, using cement-augmented CPS in high-risk groups for implant failure could be a useful technical option for reducing acute radiological complications and obtaining clinical results comparable to those obtained using SPS in patients with low risk of implant failure. LEVEL OF EVIDENCE: Level 4.

Efficacy and safety of Escherichia coli-derived recombinant human bone morphogenetic protein-2 in additional lumbar posterolateral fusion: minimum 1-year follow-up.

BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein-2 (BMP-2) is the growth factor with the most striking osteoinductive performance in orthopedic operations; it is also able to induce heterotopic bone formation. However, there has been little clinical research on Escherichia coli-derived BMP-2 (E.BMP-2). PURPOSE: To confirm the efficacy and safety of E.BMP-2 with a hydroxyapatite carrier when applied to one-sided posterolateral fusion (PLF) in addition to lumbar interbody fusion (LIF), and to measure the lower dose of E.BMP-2 ever reported achieving solid fusion. STUDY DESIGN/SETTING: Retrospective case-control study PATIENT SAMPLE: A total of 121 patients who received surgery for one or two levels of fusion for lumbar degenerative spinal stenosis or spondylolisthesis from January 2009 to December 2019 were included. OUTCOME MEASURES: Clinical and functional outcomes were evaluated using preoperative and final follow-up visual analogue scales for back pain (VAS-BP) and leg pain (VAS-LP), and Korean Oswestry disability index (K-ODI) scores. Fusion rates were evaluated by computed tomography at six months and one year after surgery. In addition, a subgroup analysis of group E according to number of fusion levels was conducted, and the fusion rates in the one-level and two-level fusion groups were compared. METHODS: LIF and additional one-sided PLF was performed in all patients. They received autogenous iliac bone grafts (Group C, n=69) or 1mg of E.BMP-2 (Group E, n=52). RESULTS: There were no significant differences between preoperative and final VAS-BP, VAS-LP and K-ODI. The PLF rate was 79.7% for Group C and 82.7% for Group E at postoperative six months, and 94.2% for Group C and 100% for Group E at postoperative one year (p =.679, 0.134, respectively). The LIF rate was 71.0% in Group C and 71.2% in Group E at six months after surgery, and 97.1% in Group C and 100% in Group E at one year (p =.987, 0.506, respectively). In terms of numbers of fusion levels in Group E, PLF rates at six months (p =.486) and one year after surgery were similar in the two groups, as were LIF rates at six months (p =.822) and one year after surgery. There were no cases of malignancy or radiculopathy in Group E during one-year of follow-up. CONCLUSIONS: One milligram of E.BMP-2 is a safe and effective osteoinductive material in short-level lumbar PLF surgery.

Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment.

The genetic basis of earlobe attachment has been a matter of debate since the early 20th century, such that geneticists argue both for and against polygenic inheritance. Recent genetic studies have identified a few loci associated with the trait, but large-scale analyses are still lacking. Here, we performed a genome-wide association study of lobe attachment in a multiethnic sample of 74,660 individuals from four cohorts (three with the trait scored by an expert rater and one with the trait self-reported). Meta-analysis of the three expert-rater-scored cohorts revealed six associated loci harboring numerous candidate genes, including EDAR, SP5, MRPS22, ADGRG6 (GPR126), KIAA1217, and PAX9. The large self-reported 23andMe cohort recapitulated each of these six loci. Moreover, meta-analysis across all four cohorts revealed a total of 49 significant (p < 5 × 10-8) loci. Annotation and enrichment analyses of these 49 loci showed strong evidence of genes involved in ear development and syndromes with auricular phenotypes. RNA sequencing data from both human fetal ear and mouse second branchial arch tissue confirmed that genes located among associated loci showed evidence of expression. These results provide strong evidence for the polygenic nature of earlobe attachment and offer insights into the biological basis of normal and abnormal ear development.

Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort.

BACKGROUND: Prenatal urinary concentrations of phthalates in women participants in an urban birth cohort were associated with outcomes in their children related to neurodevelopment, autoimmune disease risk, and fat mass at 3,5,7, and 8 years of life. Placental biomarkers and outcomes at birth may offer biologic insight into these associations. This is the first study to address these associations with candidate genes from the phthalate and placenta literature, accounting for sex differences, and using absolute quantitation methods for mRNA levels. METHODS: We measured candidate mRNAs in 180 placentas sampled at birth (HSD17B1, AHR, CGA, CYP19A1, SLC27A4, PTGS2, PPARG, CYP11A1) by quantitative PCR and an absolute standard curve. We estimated associations of loge mRNA with quartiles of urinary phthalate monoesters using linear mixed models. Phthalate metabolites (N = 358) and mRNAs (N = 180) were transformed to a z-score and modeled as independent, correlated vectors in relation to large for gestational age (LGA) and gestational diabetes mellitus (GDM). RESULTS: CGA was associated with 4 out of 6 urinary phthalates. CGA was 2.0 loge units lower at the 3rd vs. 1st quartile of mono-n-butyl phthalate (MnBP) (95% confidence interval (CI): -3.5, -0.5) in male placentas, but 0.6 loge units higher (95% CI: -0.8, 1.9) in female placentas (sex interaction p = 0.01). There was an inverse association of MnBP with PPARG in male placentas (-1.1 loge units at highest vs. lowest quartile, 95% CI: -2.0, -0.1). CY19A1, CYP11A1, CGA were associated with one or more of the following in a sex-specific manner: monobenzyl phthalate (MBzP), MnBP, mono-iso-butyl phthalate (MiBP). These 3 mRNAs were lower by 1.4-fold (95% CI: -2.4, -1.0) in male GDM placentas vs. female and non-GDM placentas (p-value for interaction = 0.04). The metabolites MnBP/MiBP were 16% higher (95% CI: 0, 22) in GDM pregnancies. CONCLUSIONS: Prenatal concentrations of certain phthalates and outcomes at birth were modestly associated with molecular changes in fetal placental tissue during pregnancy. Associations were stronger in male vs. female placentas, and associations with MnBP and MiBP were stronger than other metabolites. Placental mRNAs are being pursued further as potential mediators of exposure-induced risks to the health of the child.

Performance of the Real-Q EBV Quantification Kit for Epstein-Barr Virus DNA Quantification in Whole Blood.

There has been increasing interest in standardized and quantitative Epstein-Barr virus (EBV) DNA testing for the management of EBV disease. We evaluated the performance of the Real-Q EBV Quantification Kit (BioSewoom, Korea) in whole blood (WB). Nucleic acid extraction and real-time PCR were performed by using the MagNA Pure 96 (Roche Diagnostics, Germany) and 7500 Fast real-time PCR system (Applied Biosystems, USA), respectively. Assay sensitivity, linearity, and conversion factor were determined by using the World Health Organization international standard diluted in EBV-negative WB. We used 81 WB clinical specimens to compare performance of the Real-Q EBV Quantification Kit and artus EBV RG PCR Kit (Qiagen, Germany). The limit of detection (LOD) and limit of quantification (LOQ) for the Real-Q kit were 453 and 750 IU/mL, respectively. The conversion factor from EBV genomic copies to IU was 0.62. The linear range of the assay was from 750 to 106 IU/mL. Viral load values measured with the Real-Q assay were on average 0.54 log10 copies/mL higher than those measured with the artus assay. The Real-Q assay offered good analytical performance for EBV DNA quantification in WB.

Identification and characterization of NF1 splicing mutations in Korean patients with neurofibromatosis type 1.

Neurofibromatosis type I (NF1) is an autosomal dominant genetic disorder caused by NF1 mutations. Although mutations affecting mRNA splicing are the most common molecular defects in NF1, few studies have analyzed genomic DNA (gDNA)-mRNA correlations in Korean NF1 patients. In this study, we investigated 28 unrelated NF1 patients who showed splicing alterations in reverse transcription-PCR of NF1 mRNA and identified 24 different NF1 splicing mutations, 9 of which were novel. These mutations can be categorized into five groups: exon skipping resulting from mutations at authentic 5' and 3' splice sites (type I, 46%), cryptic exon inclusion caused by deep intronic mutations (type II, 8%), creation of new splice sites causing loss of exonic sequences (type III, 8%), activation of cryptic splice sites due to disruption of authentic splice sites (type IV, 25%) and exonic sequence alterations causing exon skipping (type V, 13%). In total, 42% of all splicing mutations did not involve the conserved AG/GT dinucleotides of the splice sites, making it difficult to identify the correct mutation sites at the gDNA level. These results add to the mutational spectrum of NF1 and further elucidate the gDNA-mRNA correlations of NF1 mutations.

Genome-wide association study of periodontal health measured by probing depth in adults ages 18-49 years.

The etiology of chronic periodontitis clearly includes a heritable component. Our purpose was to perform a small exploratory genome-wide association study in adults ages 18-49 years to nominate genes associated with periodontal disease-related phenotypes for future consideration. Full-mouth periodontal pocket depth probing was performed on participants (N = 673), with affected status defined as two or more sextants with probing depths of 5.5 mm or greater. Two variations of this phenotype that differed in how missing teeth were treated were used in analysis. More than 1.2 million genetic markers across the genome were genotyped or imputed and tested for genetic association. We identified ten suggestive loci (p-value ≤ 1E-5), including genes/loci that have been previously implicated in chronic periodontitis: LAMA2, HAS2, CDH2, ESR1, and the genomic region on chromosome 14q21-22 between SOS2 and NIN. Moreover, we nominated novel loci not previously implicated in chronic periodontitis or related pathways, including the regions 3p22 near OSBPL10 (a lipid receptor implicated in hyperlipidemia), 4p15 near HSP90AB2P (a heat shock pseudogene), 11p15 near GVINP1 (a GTPase pseudogene), 14q31 near SEL1L (an intracellular transporter), and 18q12 in FHOD3 (an actin cytoskeleton regulator). Replication of these results in additional samples is needed. This is one of the first research efforts to identify genetic polymorphisms associated with chronic periodontitis-related phenotypes by the genome-wide association study approach. Though small, efforts such this are needed in order to nominate novel genes and generate new hypotheses for exploration and testing in future studies.

PHOX2B mutations in patients with Ondine-Hirschsprung disease and a review of the literature.

Congenital central hypoventilation syndrome (CCHS), also known as Ondine's curse, is characterized by idiopathic failure of autonomic breathing and is often associated with neurocristopathies such as Hirschsprung disease (HSCR). CCHS is caused by mutations in the paired-like homeobox 2B (PHOX2B) gene, often manifest as polyalanine repeat expansions. Herein, we report the cases of two unrelated Korean patients with Ondine-Hirschsprung disease. The patient's clinical manifestations were apnea and cyanosis requiring immediate endotracheal intubation, recurrent hypoventilation with hypercapnia, hypoxia after ventilator removal, and abdominal distension since birth. Intestinal biopsies were performed and the absence of ganglion cells in the colon was consistent with HSCR. We performed direct sequencing analysis in the PHOX2B and RET genes and fluorescence polymerase chain reaction in order to determine the polyalanine tract expansion in exon 3 of the PHOX2B gene. Expansion mutations were detected in both patients; one had 20/24 repeats and the other had 20/27 repeats. The 20/24 genotype has not been previously described in severe CCHS phenotypes and associated HSCR. We believe that the information in this report will improve our understanding of the phenotypic and genotypic heterogeneities of CCHS and HSCR.