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Hyaluronic acid (HA) is the most common dermal filler in use. It improves wrinkles and volume loss not only by filling and volumizing but also by hydrating the injected area with its water affinity. It is a naturally occurring component of skin, and there is a negligible risk of immunologic or allergic reaction with injection. It is rapidly degraded by the injection of hyaluronidase, thus creating an ideal injectable material that is low risk and reversible. Its duration of effect may be longer than expected based on bioavailability of the HA product due to collagen synthesis or fibroblast stimulation.

To summarize our experience in the application of radiofrequency ablation (RFA) and microwave ablation (MWA) for selective fetal reduction in complicated monochorionic pregnancies and compare the perinatal outcome of the two techniques.This was a retrospective study of data from a consecutive cohort of all monochorionic twin pregnancies that underwent selective fetal reduction with RFA or MWA at Peking University Third Hospital, Beijing, China from January 2012 to December 2018. All surviving cotwins were followed up to assess their neurodevelopment using the Ageamp; Stage Questionnaire, Chinese version. Perinatal and neurodevelopmental outcomes were compared between the RFA and MWA groups. We also fitted multivariable models to test the association between procedure-related factors and the main perinatal outcomes, including preterm birth (PTB)lt; 37 weeks' gestation, intrauterine fetal death (IUFD) of the cotwin, adverse outcome (defined as occurrence of IUFD of the cotwin, termination of pregnancy or PTBlt; 28 weeks) and overall survival.In total, 45 cases (42 twin and three triplet pregnancies) underwent RFA and 126 cases (105 twin and 21 triplet pregnancies) underwent MWA. The overall survival rates in monochorionic diamniotic twin pregnancies were similar between the RFA and MWA groups (61.0% vs 67.0%; P = 0.494). However, pregnancies whose indication for fetal reduction was selective intrauterine growth restriction or twin reversed arterial perfusion had higher overall survival rates (75.5% and 82.6%, respectively) compared with those in other indication groups. A total of 104 children were followed up (20 in the RFA group and 84 in the MWA group); four (20.0%) and eight (9.5%) children were assessed as having overall developmental delay in the RFA and MWA groups, respectively, with no significant difference between the two groups. Multivariable analyses showed that procedure indication, number of ablation cycles and gestational age at procedure were associated significantly with the main perinatal outcomes.RFA and MWA for selective fetal reduction in complicated monochorionic pregnancies can achieve similar overall survival rate and neurodevelopmental outcome, but MWA is associated with a lower risk of preterm birth. Moreover, procedure-related factors are associated significantly with perinatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

BACKGROUND: We compared health-related quality of life (HRQOL), depressive symptoms, anxiety, and burden in caregivers of older patients with heart failure based on the intended therapy goal of the patient: awaiting heart transplantation (HT) with or without mechanical circulatory support (MCS) or prior to long-term MCS; and we identified factors associated with HRQOL. METHODS: Caregivers (n = 281) recruited from 13 HT and MCS programs in the United States completed measures of HRQOL (EQ-5D-3L), depressive symptoms (PHQ-8), anxiety (STAI-state), and burden (Oberst Caregiving Burden Scale). Analyses included ANOVA, Kruskal-Wallis tests, χ(2) tests, and linear regression. RESULTS: The majority of caregivers were female, white spouses with ≤ 2 comorbidities, median [Q1,Q3] age = 62 [57.8, 67.0] years. Caregivers (HT with MCS = 87, HT without MCS = 98, long-term MCS = 96) reported similarly high baseline HRQOL (EQ-5D-3L visual analog scale median score = 90; P = 0.67 for all groups) and low levels of depressive symptoms. STAI-state median scores were higher in the long-term MCS group vs the HT groups with and without MCS, (38 vs 32 vs 31; P < 0.001), respectively. Burden (task: time spent/difficulty) differed significantly among groups. Caregiver factors (number of comorbidities, diabetes and higher anxiety levels) were significantly associated with worse caregiver HRQOL, R(2) = 26%. CONCLUSIONS: Recognizing caregiver-specific factors, including comorbidities and anxiety, associated with the HRQOL of caregivers of these older patients with advanced HF may guide support strategies.

Partial extraction therapy (PET) is a collective concept encompassing a group of surgical techniques including socket shield, root membrane, proximal shield, pontic shield, and root submergence. PET uses the patient's own root structure to maintain blood supply derived from the periodontal ligament complex to preserve the periodontium and peri-implant tissues during restorative and implant therapy. This review aims to summarize the current knowledge regarding PET techniques and present a comprehensive evaluation of human clinical studies in the literature. Two independent reviewers conducted electronic and manual searches until January 1, 2021, in the following electronic bibliographic databases: PubMed, EMBASE, and Dentistry & Oral Sciences Source. Gray literature was searched to identify additional candidates for potential inclusion. Articles were screened by a group of 4 reviewers using the Covidence software and synthesized. A systematic search of the literature yielded 5714 results. Sixty-four articles were selected for full-text assessment, of which 42 eligible studies were included in the review. Twelve studies were added to the synthesis after a manual search of the reference lists. A total of 54 studies were examined in this review. In sum, PET techniques offer several clinical advantages: (1) preservation of buccal bone postextraction and limitation of alveolar ridge resorption, (2) mitigation of the need for invasive ridge augmentation procedures, and (3) soft-tissue dimensional stability and high esthetic outcomes. Further randomized clinical studies with larger sample sizes are needed to improve the understanding of the long-term clinical outcomes of PET.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has left patients with current or past history of cancer facing disparate consequences at every stage of the cancer trajectory. This comprehensive review offers a landscape analysis of the current state of the literature on COVID-19 and cancer, including the immune response to COVID-19, risk factors for severe disease, and impact of anticancer therapies. We also review the latest data on treatment of COVID-19 and vaccination safety and efficacy in patients with cancer, as well as the impact of the pandemic on cancer care, including the urgent need for rapid evidence generation and real-world study designs. SIGNIFICANCE: Patients with cancer have faced severe consequences at every stage of the cancer journey due to the COVID-19 pandemic. This comprehensive review offers a landscape analysis of the current state of the field regarding COVID-19 and cancer. We cover the immune response, risk factors for severe disease, and implications for vaccination in patients with cancer, as well as the impact of the COVID-19 pandemic on cancer care delivery. Overall, this review provides an in-depth summary of the key issues facing patients with cancer during this unprecedented health crisis.

Purpose To evaluate the long-term effect of subthreshold nanosecond laser (SNL) treatment on progression to late age-related macular degeneration (AMD). Design Observational extension study of a randomized, sham-controlled trial. Participants Two hundred twelve participants with bilateral large drusen. Methods The Laser Intervention in the Early Stages of AMD (LEAD) study was a 36-month trial where participants were randomized to receive SNL or sham treatment in 1 eye at 6-monthly intervals up to 30 months. After the completion of the LEAD study, the 2 largest recruiting sites offered remaining participants an opportunity to enroll in a 24-month observational extension study. This study thus examined all participants from these 2 sites who were enrolled in the LEAD study at baseline, including the additional observational data. Main Outcome Measures Time to develop late AMD, defined on multimodal imaging, between those randomized the SNL or sham treatment. Results Overall, no significant difference was found in the rate of progression over a 60-month period in those randomized to the SNL compared with the sham group (adjusted hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.36–1.09; P = 0.098), similar to the findings at 36 months in the LEAD Study. However, evidence of treatment effect modification continued to emerge based on the coexistence of reticular pseudodrusen (RPD; P = 0.007, adjusted interaction). Namely, progression was slowed significantly with SNL treatment for those without coexistent RPD (adjusted HR, 0.34; 95% CI, 0.16–0.71; P = 0.004), but it was not significantly different for those with RPD (adjusted HR, 1.81; 95% CI, 0.67–4.88; P = 0.239). Conclusions A 24-month observational extension study to the LEAD Study confirmed that SNL treatment did not significantly reduce the overall rate of progression to late AMD in a cohort with intermediate AMD. However, the persistence of a potential beneficial treatment effect in those without coexistent RPD over a longer follow-up duration of an additional 24 months without additional treatment is encouraging. These findings provide further justification for future trials to examine the potential value of SNL treatment for slowing progression in intermediate AMD.

Purpose Previously, we showed that tear fluid protects corneal epithelial cells against Pseudomonas aeruginosa without suppressing bacterial viability. Here, we studied how tear fluid affects bacterial gene expression. Methods RNA-sequencing was used to study the P. aeruginosa transcriptome after tear fluid exposure (5 h, 37 oC). Outcomes were further investigated by biochemical and physiological perturbations to tear fluid and tear-like fluid (TLF) and assessment of bacterial viability following tear/TLF pretreatment and antibiotic exposure. Results Tear fluid deregulated ~180 P. aeruginosa genes ≥8 fold versus PBS including downregulating lasI, rhlI, qscR (quorum sensing/virulence), oprH, phoP, phoQ (antimicrobial resistance) and arnBCADTEF (polymyxin B resistance). Upregulated genes included algF (biofilm formation) and hemO (iron acquisition). qPCR confirmed tear down-regulation of oprH, phoP and phoQ. Tear fluid pre-treatment increased P. aeruginosa resistance to meropenem ~5-fold (4 μg/ml), but enhanced polymyxin B susceptibility ~180-fold (1 μg/ml), the latter activity reduced by dilution in PBS. Media containing a subset of tear components (TLF) also sensitized bacteria to polymyxin B, but only ~22.5-fold, correlating with TLF/tear fluid Ca2+ and Mg2+ concentrations. Accordingly, phoQ mutants were not sensitized by TLF or tear fluid. Superior activity of tear fluid versus TLF against wild-type P. aeruginosa was heat resistant but proteinase K sensitive. Conclusion P. aeruginosa responds to human tear fluid by upregulating genes associated with bacterial survival and adaptation. Meanwhile, tear fluid down-regulates multiple virulence-associated genes. Tears also utilize divalent cations and heat resistant/proteinase K sensitive component(s) to enhance P. aeruginosa sensitivity to polymyxin B.

The opportunistic human pathogen Candida glabrata has become an increasingly important threat to human health, with infections globally characterized by high mortality rates and multidrug resistance. To face this threat, more efficient diagnostic and therapeutic approaches are required, underpinning research to help define the intraspecies epidemiology, genetic variability, and therefore, diagnostic and therapeutic target stability. Previous comparative genetics studies conducted on limited numbers of strains only revealed partial resolution of chromosomal settings. In this study, by combining short- and long-read genome sequencing, phenotypic characterization, and comparative genomics over a large set of strains, we detected strict relationships between large chromosomal rearrangements and phylogenetic clades, genes subjected to different selective pressures, and new sets of genes associated with resistance to antifungals. Overall, these results not only provide a fundamental contribution to our knowledge of C. glabrata evolution and epidemiology but may also lay the foundations for the future development of tailored therapeutic approaches.

The prevalence of hepatitis C among drug users in China is high, and thus it is one of the populations that needs attention to achieve hepatitis C elimination. However, due to the complexities of this population's situation, hepatitis C elimination still faces many challenges, such as difficult screening, low cure rate, poor compliance, and high reinfection rates. Therefore, the existing diagnostic and therapeutic system cannot meet the needs of this population. China has pledged to establish a unified system for drug users that will integrate drug treatment programs, education, medical care, and rehabilitation, creating favorable conditions for integrating hepatitis C diagnosis and treatment and improving the accessibility of drug users. Starting with the current situation and challenges of eliminating hepatitis C among drug users in China, in combination with cases from other countries, this paper discusses the strategy for eliminating hepatitis C and introduces what Hainan Province did to eliminate hepatitis C among drug users.吸毒人群丙型肝炎流行率高，是我国达成丙型肝炎消除需要重点关注的人群之一。然而由于该人群处境复杂，其丙型肝炎消除仍面临着筛查难、治疗率低、依从性差、再感染率高等诸多挑战，现有诊疗体系无法满足该人群的需求。我国致力于为吸毒人员建立戒毒管理、教育、医疗及康复为一体的统一系统，这也为整合丙型肝炎诊疗、提高吸毒人群的诊疗可及性提供了有力条件。现从我国吸毒人群丙型肝炎消除的现状及挑战出发，结合国外案例，探讨该人群中丙型肝炎消除策略，并介绍海南省针对吸毒人群的丙型肝炎消除经验。.

This study reviewed the concepts and properties of the receiver operating characteristic (ROC) curve and precision recall (PR) curve, and made suggestions on the application of two curves based on the prevalence in combination with the results of simulation data. This study demonstrated that the ROC curve and PR curve had different properties, which could reflect the performance of diagnostic methods from various aspects. These two curves should be selected with a consideration of prevalence and clinical scenarios. When the prevalence was less than 20%, especially less than 5%, the PR curve could be adopted.本研究对受试者特征工作（ROC）曲线和查准率-查全（PR）曲线的概念和性质进行概括回顾，结合模拟数据结果，基于患病率对ROC曲线和PR曲线的应用做出建议。研究显示，ROC曲线和PR曲线具有不同的性质，可以从不同的侧面反映诊断方法的性能，应结合患病率和临床场景进行选择。当患病率小于20%，尤其是小于5%时，应重视PR曲线的应用。.

Summary Background Since the emergence of the COVID-19 pandemic in late 2019, various public health and social measures (PHSMs) have been used to suppress and mitigate the spread of SARS-CoV-2. With mass vaccination programmes against COVID-19 being rolled out in many countries in early 2021, we aimed to evaluate to what extent travel restrictions and other PHSMs can be relaxed without exacerbating the local and global spread of COVID-19. Methods We adapted an existing age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission dynamics that can be parameterised with country-specific age demographics and contact patterns to simulate the effect of vaccination and PHSM relaxation on transmission. We varied assumptions by age-specific susceptibility and infectiousness, vaccine uptake, contact patterns, and age structures. We used Hong Kong as a case study and assumed that, before vaccination, the population is completely susceptible to SARS-CoV-2 infection. We applied our model to 304 jurisdictions (27 countries and 277 sub-national administrative regions from eight countries). We assumed that PHSMs have suppressed the effective reproductive number (Re) to fall between 1·0 and 9·0 locally before the commencement of vaccination programmes. We evaluated the levels of PHSMs that should be maintained during the roll-out of COVID-19 vaccination to avoid a large local outbreak of COVID-19, with different assumptions about vaccine efficacy, vaccination coverage, and travel restrictions. We assumed that the maximum capacity of the health system, in terms of daily hospital admissions, is 0·005% of the population size. Findings At vaccine efficacy of 0·80 in reducing susceptibility to SARS-CoV-2 infection, 0·50 in reducing SARS-CoV-2 infectivity, and 0·95 in reducing symptomatic COVID-19 diseases, vaccination coverage would have to be 100% for all individuals aged 30 or older to avoid an outbreak, when relaxing PHSMs, that would overload the local health-care system, assuming a pre-vaccination Re of 2·5. Testing and quarantine of at least 5 days would have to be maintained for inbound travellers to minimise the risk of reintroducing a local outbreak until high vaccination coverages are attained locally and overseas in most countries. Interpretation Gradual relaxation of PHSMs should be carefully planned during the roll-out of vaccination programmes, and easing of travel restrictions weighed against risk of reintroducing outbreaks, to avoid overwhelming health systems and minimise deaths related to COVID-19. Funding Health and Medical Research Fund and the General Research Fund.

Older age cleft palate (CP) repair in international settings has been associated with increased surgical morbidity. This study assesses the prevalence and risks associated with late-age CP repair (age 5 years) in the United States.Primary CP repair patients less than the age of 18 years were identified in the National Surgical Quality Improvement pediatric database from 2012 to 2018. Total postoperative complications, readmissions, reoperations, duration of surgery, and length of stay were recorded. T-tests and χA total of 10,022 primary CP procedures were identified from 2012 to 2018, of which 868 (8.6%) received repair at age 5 years. Hispanic patients constituted a larger proportion of CP repair from ages 11 to 17 years than repair at other ages (P .001). In comparison with children treated from ages 0 to 5 years, children operated on between ages 6 and 10 or 11 and 17 years experienced no increases in unplanned readmissions, reoperations, or complication rates after surgery. Patients of ages 6-10 years and 11-17 years had decreased operating room time (P .001) compared with younger patients. Patients of ages 11-17 years also had decreased hospital length of stay (P = .04).Many children in the United States received primary CP repair after the age of 5 years likely due to late treatment of submucosal clefts or delayed care among international immigrants/adoptees. Old age procedures were not associated with increased short-term surgical morbidity in comparison with surgery at earlier time points. The causes and implications of older age primary surgery warrant further study.

The serum 25-hydroxyvitamin D [25(OH)D] is recommended by various management agencies for evaluating the nutritional status of vitamin D (VitD). However, 25(OH)D cannot reflect the actual composition and activity of VitD in vivo. This study used UPLC-MS/MS to detect the levels of serum VitD metabolites in some special populations, so as to clarify its importance in accurately evaluating VitD storage in vivo.A total of 2029 subjects were enrolled, including 1204 cases in minor health (MH), 467 in the minor disease (MD), 119 in the adult health (AH) and 239 in adult disease (AD). Serum VitD2 and VitD3 levels were measured by UPLC-MS/MS. Serum C3-epi concentrations were also measured in 144 subjects by a spot check method.There were significant differences in the levels of VitD2, VitD3 and 25(OH)D among groups (all p0.001). According to serum level of 25(OH)D, percentage of subjects with sufficient VitD in the MH, MD, AH and AD group were 65.4%, 52.7%, 29.4% and 20.9%, respectively. After converting VitD2 activity to AVitD3, subjects with sufficient VitD in MH, MD, AH and AD group accounted for 53.2%, 40.9%, 17.7% and 11.3%, respectively. C3-epi levels in the MH (z = 7.49, p0.001), MD (z = 7.03, p0.001) and AD group (z = 4.68, p0.001) were higher than that in the AH group.Not only the serum 25(OH)D level, but also the simultaneous detection of VitD2 and VitD3 levels will overestimate the VitD storage in some subjects. Accurate evaluation of VitD storage in these individuals also requires detection of C3-epi levels.

Chimeric antigen receptor (CAR) T cell therapies targeting single antigens have performed poorly in clinical trials for solid tumors due to heterogenous expression of tumor-associated antigens (TAAs), limited T cell persistence, and T cell exhaustion. Here, we aimed to identify optimal CARs against glypican 2 (GPC2) or CD276 (B7-H3), which were highly but heterogeneously expressed in neuroblastoma (NB), a lethal extracranial solid tumor of childhood. First, we examined CAR T cell expansion in the presence of targets by digital droplet PCR. Next, using pooled competitive optimization of CAR by cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq), termed P-COCC, we simultaneously analyzed protein and transcriptome expression of CAR T cells to identify high-activity CARs. Finally, we performed cytotoxicity assays to identify the most effective CAR against each target and combined the CARs into a bicistronic "OR" CAR (BiCisCAR). BiCisCAR T cells effectively eliminated tumor cells expressing GPC2 or CD276. Furthermore, the BiCisCAR T cells demonstrated prolonged persistence and resistance to exhaustion when compared with CARs targeting a single antigen. This study illustrated that targeting multiple TAAs with BiCisCAR may overcome heterogenous expression of target antigens in solid tumors and identified a potent, clinically relevant CAR against NB. Moreover, our multimodal approach integrating competitive expansion, P-COCC, and cytotoxicity assays is an effective strategy to identify potent CARs among a pool of candidates.

Synthetic hydroxyapatite (HA) and its related materials have made great progress in basic research and clinical application in spinal repair and reconstruction. However, the effect of HA and its composites used in spinal fusion still remained controversial. This meta-analysis aimed at evaluating the efficacy and safety of HA compared with autologous bone.A systematic search in PubMed, MEDLINE, China National Knowledge Internet, EMBASE, and the Cochrane Library was conducted for relevant studies from inception until May 2021. Studies investigating the application of HA and its related composites in spinal fusion were selected for analysis.The operation time of patients treated with artificial bone containing HA was less than that of patients with autologous bone (p = 0.02). The amount of operative blood loss in patients in the HA group was less than that in the autograft group (p = 0.007). Patients treated with autologous bone got a more significant advantage in fusion rate at 6 months (p = 0.009). Nevertheless, there was no significant difference in the fusion rate between patients in the two groups at 12 months or no less than 24 months postoperatively (p = 0.24; p = 0.87). Compared to the autograft group, the HA group significantly decreased postoperative adverse events (p = 0.03). Furthermore, there was no significant difference in the Oswestry Disability Index (p = 1.00) nor the Visual Analogue Scale score (p = 0.94) between the two groups.This meta-analysis suggests that the clinical application of HA and its related composite materials in spinal reconstruction is comparable to that of autologous bone, with satisfactory efficacy and safety.

A patient complained of ophthalmology with poor vision in both eyes for more than 30 years and aggravation for more than 2 years. The central anterior lens capsule was found to have a conical protrusion under a slit-lamp microscope after pupil dilation in both eyes. The diagnosis was bilateral cataract and congenital anterior lenticonus. Phacoemulsification cataract extraction combined with intraocular lens implantation was performed. The visual acuity in both eyes was significantly better after surgery.1例主诉为双眼视力欠佳30余年、加重2年余患者就诊眼科。散瞳后裂隙灯显微镜下可见双眼晶状体前囊膜中央部向前呈圆锥状突出。诊断为双眼白内障、双眼先天性前圆锥形晶状体。分别于局部麻醉下行双眼超声乳化白内障吸除人工晶状体植入术，术后双眼视力较前明显好转。.

The clinical case series presents a minimally invasive modified tunnel procedure with autogenous connective tissue graft (CTG) using a V-reverse sutures to treat multiple gingival recessions.In periodontal and peri-implant plastic procedures, proper graft and flap stabilization are crucial in the outcomes. The coronally advanced flap allows for better access with the possibility of suturing the graft to the de-epithelialized papillae of the periosteum; there is little evidence with using the V-reverse sutures technique in stabilizing the graft and the flap when performing tunnel techniques (TUN). The following case series presents a minimally invasive modified tunnel procedure with autogenous CTG using V-reverse sutures to treat gingival recessions.Three patients with Miller Class I maxillary buccal gingival recessions defects were selected for this study. All subjects were treated with the minimally invasive modified tunnel technique with autogenous subepithelial CTG. V-reverse sutures technique was performed to further improve the stability of the graft at the recipient site. Clinical parameters, including mean recession depth and root coverage esthetic score (RES), were recorded at baseline, 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1-year postoperative follow-up visits.At the 1-year follow-up, complete root coverage was achieved in multiple gingival recessions defect sites. In conclusion, this technique represents an alternative treatment for Miller Class I gingival recessions defects with clinical and esthetically satisfactory outcomes.Combining the advantages of V-reverse sutures and CTG in the treatment of gingival recessions is feasible and noninvasive.

To examine opioid prescribing and consumption patterns after hysterectomy and identify factors associated with postoperative opioid consumption.Prospective cohort study.Single university medical center.Women undergoing hysterectomy for benign, nonobstetric indications.Participant preoperative and surgical characteristics were obtained through chart review and patient report of baseline pain score. During the third postoperative week, participants completed a telephone interview, including a direct count of remaining opioid pills and assessment of satisfaction with pain management. We assessed factors associated with opioid consumption in oral morphine equivalents (OME) using a linear regression model.Of the 129 participants, 113 (88%) completed the postoperative survey after hysterectomy: 16 vaginal, 43 robotic-assisted, 42 conventional laparoscopic, and 12 abdominal hysterectomies. The median amount of opioid prescribed was 150 OME (interquartile range [IQR] 113-200), while the median amount consumed was 75 (IQR 10-135), reflecting an average consumption of about 50% of the prescription. Opioid prescription size was associated with consumption; for every additional oral morphine equivalent prescribed, on average, an additional 0.5 was consumed (p.001). If the indication for hysterectomy was related to pain, participants consumed 25.3 additional OME (p = .04). The amount of opioid prescribed was inversely correlated with pain management satisfaction; every additional point on a 1 through 5 Likert scale of increasing satisfaction was associated with 44 fewer OME prescribed (standard error 9 OME, p.001). For the 1464 total unused pills among the 104 participants with leftover opioids, only 20% reported an Food and Drug Administration -compliant opioid disposal plan.Gynecologic surgeons can respond to the opioid epidemic by reducing excess opioid pills after hysterectomy by providing both the smallest effective prescription size and concrete resources for safe opioid disposal. These actions may contribute to a reduction in opioid use disorder cases or overdose deaths.

Background The nonavalent human papillomavirus (HPV) vaccine has been shown to extend protection against oncogenic HPV types 31/33/45/52/58 (HPV-OV) not covered by the bivalent and quadrivalent HPV vaccines. Besides its clinical benefit, evidence on the economic value of the nonavalent vaccine is required to inform local vaccination strategies and funding decisions. This study evaluated the cost-effectiveness of replacing the bivalent vaccine with the nonavalent vaccine in the national school-based HPV vaccination programme in Singapore. Methods An existing age-structured dynamic transmission model coupled with stochastic individual-based simulations was adapted to project the health and economic impact of vaccinating 13-year-old girls with two doses of the nonavalent or bivalent HPV vaccines in Singapore. Direct costs (in Singapore dollars, S$) were obtained from public healthcare institutions in Singapore, while health state utilities were sourced from the literature. Incremental cost-effectiveness ratios (ICERs) were estimated over a lifetime horizon, from a healthcare system perspective. Probabilistic sensitivity analysis was performed to obtain the ICERs and corresponding variations across variable uncertainty. Particularly, this study tested the scenarios of lifelong and 20-year vaccine-induced protection, assumed 96.0% and 22.3% cross-protection against HPV-OV by nonavalent and bivalent vaccines respectively, and fixed vaccine prices per dose at S$188 for nonavalent and S$61.50 for bivalent vaccines. Results Compared with the bivalent vaccine, the use of the nonavalent vaccine was associated with an ICER of S$61,629 per quality-adjusted life year gained in the base case. The result was robust across a range of plausible input values, and to assumptions regarding the duration of vaccine protection. Conclusion Given the high ICER, the nonavalent vaccine is unlikely to represent a cost-effective option compared with the bivalent vaccine for school-based HPV vaccination of 13-year old female students in Singapore. Substantial price reductions would be required to justify its inclusion in the school-based programme in the future.

Health systems capture injuries using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Clinical Modification (ICD-10-CM) diagnostic codes and share data with public health to inform injury surveillance. This study analyses provider-assigned ICD-10-CM injury codes among self-reported injuries to determine the effectiveness of ICD-10-CM coding in capturing injury and assault.MethodsSelf-reported injury screen records from an urban, level 1 trauma centre collected between 20 November 2015 and 30 September 2019 were compared with corresponding provider-assigned ICD-10-CM codes discerning the frequency in which intentions are indicated among patients reporting (1) any injury and (2) assault.ResultsOf 380 922 patients screened, 32 788 (8.61%) reported any injury and 6763 (1.78%) reported assault. ICD-10-CM codes had a sensitivity of 67.40% (95% CI 66.89% to 67.91%) for any injury and specificity of 89.79% (95% CI 89.69% to 89.89%]). For assault, ICD-10-CM codes had sensitivity of 2.25% (95% CI 1.91% to 2.63%) and specificity of 99.97% (95% CI 99.97% 99.98%).DiscussionThis study found provider-assigned ICD-10-CM had limited sensitivity to identify injury and low sensitivity for assault. This study more fully characterises ICD-10-CM coding system effectiveness in identifying assaults.

Author(s): Magbanua, MJM; Swigart, LB; Wu, H-T; Hirst, GL; Yau, C; Wolf, DM; Tin, A; Salari, R; Shchegrova, S; Pawar, H; Delson, AL; DeMichele, A; Liu, MC; Chien, AJ; Tripathy, D; Asare, S; Lin, C-HJ; Billings, P; Aleshin, A; Sethi, H; Louie, M; Zimmermann, B; Esserman, LJ; van 't Veer, LJ | Abstract: BackgroundPathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is strongly associated with favorable outcome. We examined the utility of serial circulating tumor DNA (ctDNA) testing for predicting pCR and risk of metastatic recurrence.Patients and methodsCell-free DNA (cfDNA) was isolated from 291 plasma samples of 84 high-risk early breast cancer patients treated in the neoadjuvant I-SPY 2 TRIAL with standard NAC alone or combined with MK-2206 (AKT inhibitor) treatment. Blood was collected at pretreatment (T0), 3 weeks after initiation of paclitaxel (T1), between paclitaxel and anthracycline regimens (T2), or prior to surgery (T3). A personalized ctDNA test was designed to detect up to 16 patient-specific mutations (from whole-exome sequencing of pretreatment tumor) in cfDNA by ultra-deep sequencing. The median follow-up time for survival analysis was 4.8 years.ResultsAt T0, 61 of 84 (73%) patients were ctDNA positive, which decreased over time (T1: 35%; T2: 14%; and T3: 9%). Patients who remained ctDNA positive at T1 were significantly more likely to have residual disease after NAC (83% non-pCR) compared with those who cleared ctDNA (52% non-pCR; odds ratio 4.33, Pn= 0.012). After NAC, all patients who achieved pCR were ctDNA negative (nn= 17, 100%). For those who did not achieve pCR (nn= 43), ctDNA-positive patients (14%) had a significantly increased risk of metastatic recurrence [hazard ratio (HR) 10.4; 95% confidence interval (CI) 2.3-46.6]; interestingly, patients who did not achieve pCR but were ctDNA negative (86%) had excellent outcome, similar to those who achieved pCR (HR 1.4; 95% CI 0.15-13.5).ConclusionsLack of ctDNA clearance was a significant predictor of poor response and metastatic recurrence, while clearance was associated with improved survival even in patients who did not achieve pCR. Personalized monitoring of ctDNA during NAC of high-risk early breast cancer may aid in real-time assessment of treatment response and help fine-tune pCR as a surrogate endpoint of survival.

INTRODUCTION Optimal age at surgery in nonsyndromic sagittal craniosynostosis continues to be debated. Previous reports suggest that earlier age at whole vault cranioplasty more frequently requires reoperation. It is unknown, however, whether reoperation affects neurocognitive outcome. This study examined the impact of reoperation on neurocognitive outcome in children with nonsyndromic sagittal craniosynostosis using comprehensive neurocognitive testing. METHODS Forty-seven school-age children (age 5-16 years) with nonsyndromic sagittal craniosynostosis who underwent whole-vault cranioplasty were included in this analysis. Participants were administered a battery of standardized neuropsychological testing to measure neurocognitive outcomes. RESULTS Thirteen of the 47 participants underwent reoperation (27.7%); 11 out of the 13 reoperations were minor revisions while 2 reoperations were cranioplasties. Reoperation rate was not statistically different between patients who had earlier surgery (at age ≤6 months) versus later surgery (at age >6 months) (P > 0.05). Nonreoperated patients who had only one later-in-life surgery did not perform statistically better than reoperated patients on any outcome measure of neurocognitive function, including IQ, academic achievement, visuomotor integration, executive function, and behavior. Comparing reoperated earlier surgery patients with nonreoperated later surgery patients, reoperated earlier surgery patients had higher full-scale and verbal IQ (P

本例报道1例发生于中年男性的巨大鼓室球体瘤（glomus tympanicum tutor，GTME）。患者，男，48岁，因“左侧嘴角歪斜半个月”就诊，术前MRI示，左侧颞骨颅内见类圆形稍短TI稍短T2异常信号肿块，提示鼓室球体瘤。在全身麻醉下行肿物完整切除手术，大体检查示：肿瘤大小2.4 cm×2.7 cm×3.0 cm，无包膜，切面暗红色，质地韧，术后病理诊断为GTME。术后1周出院，出院后随访3年未见肿物复发，预后良好。.

OBJECTIVE: To explore the incidence of ischemic stroke after the onset of type 2 diabetes, and further analyze the risk factors, so as to provide a basis for further research. METHODS: The data were obtained from the database of the Beijing Urban Employee Basic Medical Insurance Database. The study used a prospective design to describe the incidence of ischemic stroke in patients with type 2 diabetes. In our study, these patients were followed up for seven years. Multivariate Logistic regression models were used to analyze the risk factors of ischemic stroke in patients with type 2 diabetes. RESULTS: A total of 185 813 newly diagnosed type 2 diabetes patients were enrolled, with an average age of (58.5±13.2) years, and 49.0% of them were males. A total of 10 393 patients with newly diagnosed ischemic stroke occurred in 7 years, with a cumulative incidence of 5.6% and an incidence density of 8.1/1 000 person-years. Ischemic stroke occurred in all age groups in patients with type 2 diabetes. The cumulative incidence was 1.5% (95%CI: 1.3%-1.6%) in group ≤44 years old, 3.6% (95%CI: 3.4%-3.7%) in group 45-54 years old, 5.4% (95%CI: 5.2%-5.5%) in group 55-64 years old, and 9.2% (95%CI: 9.0%-9.4%) in group ≥65 years old, and the cumulative incidence increased with age (P < 0.05). Cumulative incidence rate of the males (6.8%, 95%CI: 6.7%-7.0%) was higher than the females (4.4%, 95%CI: 4.3%-4.6%). Among the patients < 80 years old, the cumulative incidence rate of the males was higher than that of the females in all the age groups. In the patients ≥80 years of age, the cumulative incidence was higher in the females (9.2%) than in the males (7.9%). Further analysis revealed that complications, such as coronary heart disease (OR=3.18, 95%CI: 2.72-3.72), heart failure (OR=1.53, 95%CI: 1.32-1.79) and kidney failure (OR=1.45, 95%CI: 1.20-1.75) were associated with ischemic stroke in the patients with type 2 diabetes. CONCLUSION: The incidence level of ischemic stroke in patients with type 2 diabetes is high. It is necessary to strengthen the management of risk factors in elderly patients, screen the complications of type 2 diabetes as early as possible, and take active preventive and control measures.

Digital communication platforms have had an impact on plastic surgery research. Although neurocognitive testing is an important tool for understanding the long-term developmental outcomes of congenital craniofacial conditions, testing has been geographically limited because of its interactive nature. Virtual neurocognitive testing is a facsimile version of in-person testing that allows researchers to overcome this limitation with high fidelity. Ten school-age subjects completed a neurocognitive assessment battery measuring intelligence quotient, academic achievement, and visuomotor skills at an average age of 7.8 ± 1.4 years. The subjects then retook the same battery through an identical virtual testing method approximately 1 year after the initial test. There were no significant differences in verbal intelligence quotient (p = 0.878), performance intelligence quotient (p = 0.813), and full-scale intelligence quotient (p = 0.982) scores obtained through in-person and virtual tests. There were no significant differences between academic achievement letter and word recognition (p = 0.999), math computation (p = 0.619), reading comprehension (p = 0.963), and spelling (p = 0.344) scores. There were no significant differences in visuomotor integration (p = 0.158), visual perception (p = 0.798), and motor coordination (p = 0.796) scores obtained through the two methods. The median at-home time to set up study equipment for the virtual testing was 5.0 minutes (interquartile range, 2.3 minutes). Seventy percent of participants reported that they preferred participating in research from home. All participants stated that the virtual research study was an overall positive experience. Virtual neurocognitive testing is an effective method of performing high-fidelity neurocognitive assessments while overcoming geographic barriers.

It has been over 1 year since we observed the policing of the George Floyd protests in the United States [R. R. Hardeman, E. M. Medina, R. W. Boyd, N. Engl. J. Med. 383, 197–199 (2020)]. Multiple injury reports emerged in medical journals, and the scientific community called for law enforcement to discontinue the use of less-lethal weapons [E. A. Kaske et al. , N. Engl. J. Med . 384, 774–775 (2021) and K. A. Olson et al. , N. Engl. J. Med. 383, 1081–1083 (2020)]. Despite progress in research, policy change has not followed a similar pace. Although the reasoning for this discrepancy is multifactorial, failure to use appropriate language may be one contributing factor to the challenges faced in updating policies and practices. Here, we detail how language has the potential to influence thinking and decision-making, we discuss how the language of less-lethal weapons minimizes harm, and we provide a framework for naming conventions that acknowledges harm.

Long-term repeated regular blood donation may result in the loss and deficiency of iron. Epidemiological studies have indicated that blood donation frequency, demographical characteristics, and genetic factors are associated with iron deficiency. Our review summarizes the progress in research of etiology of iron deficiency in blood donors and intervention measures to provide evidence for the health management of non-remunerated blood donors in China.献血者长期重复献血可能导致铁元素的流失和缺乏。流行病学研究表明，长期重复献血者发生铁缺乏与献血频率、人口学因素及遗传学因素间可能存在关联。本文综述了献血者铁缺乏的病因学及干预措施的研究进展，以期为我国无偿献血者健康管理提供科学依据。.

With the progress of globalization, the public health emergencies represented by major infectious diseases have become a major challenge for the public health management in China. The article briefly describes the emergency response capability assessment tools in China, and introduces two emergency response assessment tools with complete content structure and wide application in the world. Then the advantages and disadvantages of the tools are compared and discussed in order to provide reference for improvement of the assessment tools for public health emergency response capability in China.随着全球化进程推进，以重大传染病疫情为代表的突发公共卫生事件已成为国家应急管理的一大挑战。文章简述了我国的应急管理能力评估工具，介绍国际上两种内容架构完整且应用范围广泛的应急管理能力评估工具，并比较、讨论不同评估工具的优劣，以期为我国完善突发公共卫生事件应急管理能力评估工具提供参考。.

The aim of the present study was to explore the epidemiological characteristics and treatment of traumatic dental injuries of primary dentition (TDI-p) in Xi'an, China.Data of children with TDI-p admitted between January 2018 and December 2019 at the Department of Pediatric Dentistry, Xi'an Jiaotong University Stomatology Hospital were retrospectively analysed. The epidemiological distribution characteristics and related treatment information of TDI-p were described.Compared with permanent dentition, TDI-p has its particularities, such as type of trauma, treatment procedure, and behavioural management. More attention should be paid to TDI-p by both dentists and guardians.

Background Labiaplasty is an increasingly popular procedure performed for both cosmetic and pathologic etiologies. Questions have been raised regarding the efficacy of the procedure, especially for cosmetic etiologies. Objectives The aim of this study was to examine the complication profiles of labiaplasties for both cosmetic and pathologic etiologies. Methods The 2005 to 2017 National Surgical Quality Improvement Program database was analyzed for patients who, according to the relevant Current Procedural Terminology code, had undergone labiaplasties. Our cohort was further separated into cosmetic and pathologic groups based on International Classification of Diseases codes. Information was collected on patient demographic characteristics, patient comorbidities, and operative variables. Outcomes of interest included surgical complications and delayed length of stay (DLOS). A univariate analysis and multivariate logistic regression were applied to determine statistically significant predictors of our outcomes of interest for both etiologies. Results There were 640 patients in the cosmetic cohort and 1919 patients in the pathologic cohort. There were no significant differences in rates of surgical complications between the 2 groups, but there was a statistically significant increase in length of stay for the pathologic group. Univariate analysis revealed operative time and plastic surgeon specialty to be predictive of DLOS in the cosmetic cohort. No covariates were implicated with multivariate analysis for either surgical complications or for DLOS in the cosmetic cohort. Conclusions Our findings suggest that cosmetic labiaplasty is a safe and efficacious procedure with low complication rates and no predictors of adverse outcomes. Level of Evidence: 4

In a large observational study in patients with COVID-19 and cancer, survival was not significantly influenced by receipt of COVID-19 treatments, except hydroxychloroquine plus any other treatment, which was associated with reduced survival., Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. Significance: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access. This article is highlighted in the In This Issue feature, p. 1426

Unilateral coronal nonsyndromic craniosynostosis is associated with asymmetric skull growth, which may influence cerebral long-term function. Twenty affected adolescents who underwent cranial vault remodeling at a mean age of 8.2 months (12 from the Yale Craniofacial Clinic and eight from the Children's Hospital of Philadelphia) all completed a double-blinded neurodevelopmental assessment at an average age of 12.1 years. The study cohort included 55 percent female and 50 percent right-sided craniosynostosis. Mean verbal intelligence quotient was highest at 117.3, and mean performance intelligence quotient was 106.4, for a mean full-scale intelligence quotient of 112.5. Patients performed above the national average on all academic achievements except for numerical operations, which was significantly lower than word reading (p = 0.022). Patients performed below average on all Beery-Buktenica visual motor tests; motor-coordination was poorer than both visual motor integration and visual perception (p = 0.027 and p = 0.005). Significant positive correlations existed between paternal education/visual perception (r = 0.450; p = 0.046) and household income/verbal intelligence quotient (r = 0.628; p = 0.004). Patients with right unilateral coronal nonsyndromic craniosynostosis had improved spelling compared with left-sided patients on multivariate regression (p = 0.033). Female patients had higher motor coordination (p = 0.024). Breast-fed patients had better performance intelligence quotient (p = 0.024), visual motor integration (p = 0.014), and visual perception (p = 0.031). Adolescents who underwent cranial vault remodeling at two institutions had above average intelligence quotient scores, but worse mathematical and visual motor achievement compared with control subjects. Left-side craniosynostosis patients performed worse in spelling than right-side patients. Breast-feeding was an independent predictor for improved performance intelligence quotient, visual motor achievement, and visual perception performance. Study findings are limited by the cohort size. A larger population study is required, which could validate or modify the study conclusions.

Summary Background Patients with plaque psoriasis treated with biologic therapies need more efficacious, safe and convenient treatments to improve quality of life. Risankizumab and secukinumab inhibit interleukin‐23 and interleukin‐17A, respectively, and are effective in adult patients with moderate‐to‐severe plaque psoriasis but have different dosing regimens. Objectives To compare directly the efficacy and safety of risankizumab vs. secukinumab over 52 weeks. Methods IMMerge was an international, phase III, multicentre, open‐label, efficacy–assessor‐blinded, active‐comparator study, in which adult patients with chronic, moderate‐to‐severe plaque psoriasis were randomized in a 1 : 1 ratio to treatment with risankizumab 150 mg or secukinumab 300 mg. Primary efficacy endpoints were the proportions of patients achieving ≥ 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) at week 16 (noninferiority comparison with margin of 12%) and week 52 (superiority comparison). Results In total 327 patients from nine countries were treated with risankizumab (n = 164) or secukinumab (n = 163). Risankizumab was noninferior to secukinumab in the proportion of patients achieving PASI 90 at week 16 [73·8% vs. 65·6%; difference of 8·2%, 96·25% confidence interval (CI)−2·2 to 18·6; within the 12% noninferiority margin] and superior to secukinumab at week 52 (86·6% vs. 57·1%; difference of 29·8%, 95% CI 20·8–38·8; P < 0·001), thus meeting both primary endpoints. All secondary endpoints (PASI 100, static Physician's Global Assessment 0 or 1, and PASI 75) at week 52 demonstrated superiority for risankizumab vs. secukinumab (P < 0·001). No new safety concerns were identified. Conclusions At week 52, risankizumab demonstrated superior efficacy and similar safety with less frequent dosing compared with secukinumab., What is already known about this topic? The need remains for treatments with sustained efficacy and a more convenient dosing schedule in moderate‐to‐severe psoriasis.Risankizumab and secukinumab are indicated for the treatment of adults with moderate‐to‐severe plaque psoriasis and target interleukin‐23 and interleukin‐17, respectively.To date, risankizumab and secukinumab have not been directly compared. What does this study add? IMMerge directly compared the safety and efficacy of risankizumab and secukinumab in patients with moderate‐to‐severe plaque psoriasis using ≥ 90% improvement in Psoriasis Area and Severity Index at weeks 16 (noninferiority) and 52 (superiority) as primary endpoints.In terms of efficacy risankizumab was noninferior to secukinumab at week 16 and superior to secukinumab at week 52 of treatment based on primary endpoint analyses. The two medications had a similar safety profile. Linked Comment: Schmitt-Egenolf. Br J Dermatol 2021; 184: 3–4. Plain language summary available online

Background: People with schizophrenia have higher rates of smoking than the general population, and lower quit rates. Several randomised controlled trials have investigated the effectiveness of pharmacological interventions for smoking cessation over the past 20 years. We did a systematic review and pairwise and network meta-analysis of smoking abstinence to guide decision making in offering pharmacological interventions for smoking cessation for people with schizophrenia spectrum disorders. Methods: We systematically reviewed PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and China National Knowledge Infrastructure from inception to Sept 30, 2019, for randomised controlled trials of varenicline, bupropion, and nicotine replacement therapy for smoking cessation for people with schizophrenia spectrum disorders or psychotic disorders who were smokers at the time of study recruitment. Data were extracted from published studies on smoking abstinence outcomes and psychotic symptoms. We did pairwise and network meta-analyses for the primary outcome of smoking abstinence. Sensitivity analyses were done on study inclusion criteria, duration, quality, and location. This study is registered with the international prospective register of systematic reviews PROSPERO, CRD42018102343. Findings: A total of 15 111 records were identified by the database searches, and 163 full-text articles were assessed for eligibility. 145 articles were then excluded for several reasons including insufficient data, or abstracts published in later studies, and 18 studies were included in the meta-analysis. In the pairwise meta-analyses, four studies with 394 participants assessed varenicline (RR 3·75, 95% CI 1·96–7·19, p2=0%), four studies with bupropion and 292 participants (RR 3·40, 95% CI 1·58–7·34, p=0·0002; I2=0%), and three studies with 561 participants assessed nicotine replacement therapy (RR 4·27, 95% CI 1·71–10·65, p=0·0002; I2=0%). All three treatments were deemed superior to placebo. In the network meta-analysis, varenicline was superior to bupropion (RR 2·02, 95% CI 1·04–3·93; p=0·038) but no significant difference was found between varenicline and nicotine replacement therapy, or bupropion and nicotine replacement therapy. No agents were associated with changes in psychiatric symptoms, but varenicline was associated with higher rates of nausea than was placebo. Interpretation: We found evidence to support use of pharmacological agents for smoking cessation for people with psychosis. Varenicline might be superior to bupropion; however, additional direct testing and combination trials of pharmacological agents for smoking cessation are required to inform clinical decision making for people with psychosis. Funding: None.

Objectives Diabetes mellitus (DM) is a serious public health issue worldwide, and DM patients have higher risk of cardiovascular diseases (CVDs), which is the leading cause of DM-related deaths. China has the largest DM population, yet a robust model to predict CVDs in Chinese DM patients is still lacking. This systematic review is carried out to summarize existing models and identify potentially important predictors for CVDs in Chinese DM patients. Study design Systematic review. Methods Medline and Embase were searched for data from April 1st, 2011 to May 31st, 2018. A study was eligible if it developed CVD (defined as total CVD or any major cardiovascular component) risk prediction models or explored potential predictors of CVD specifically for Chinese people with type 2 DM. Standardized forms were utilized to extract information, appraise applicability, risk of bias, and availabilities. Results Five models and 29 studies focusing on potential predictors were identified. Models for a primary care setting, or to predict total CVD, are rare. A number of common predictors (e.g. age, sex, diabetes duration, smoking status, glycated hemoglobin (HbA1c), blood pressure, lipid profile, and treatment modalities) were observed in existing models, in which urine albumin:creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) are highly recommended for the Chinese population. Variability of blood pressure (BP) and HbA1c should be included in prediction model development as novel factors. Meanwhile, interactions between age, sex, and risk factors should also be considered. Conclusions A 10-year prediction model for CVD risk in Chinese type 2 DM patients is lacking and urgently needed. There is insufficient evidence to support the inclusion of other novel predictors in CVDs risk prediction functions for routine clinical use.

Summary Background Complex spine surgery in patients with major comorbidities leads to increased need for midline back wound reconstruction by plastic surgeons. Literature suggests that back wound reconstruction concurrent with high-risk immediate/index spine surgery may lead to fewer complication. This study aimed to validate this claim in a large cohort treated at a tertiary center. We hypothesize that immediate reconstruction may lead to fewer adverse events in comparison to delayed reconstruction. Methods This was a retrospective single-center review of 659 patients who underwent spinal surgery with/without reconstruction by plastic surgeons between November 2011 and December 2015. Three main cohorts were evaluated: patients who underwent spinal surgery with no reconstruction, patients with delayed reconstruction after spine surgery, and patients with immediate back wound reconstruction with index spine surgery. Demographic, clinical, and outcomes data were collected from electronic medical records. Primary endpoints were the incidence of any complications such as dehiscence, infection, seroma/hematoma, and exposed hardware. The secondary endpoint was return to the operating room and most recent follow-up. Results Forty-three patients underwent index reconstruction (follow-up 25.3 ± 12.7 months), 33 were delayed (follow-up 23.7 ± 12.5 months), and 583 had no reconstruction (follow-up 22.1 ± 15.2 months). Patients who underwent index reconstruction had more spinal levels involved than delayed reconstruction (7.8 ± 0.75 vs 5.6 ± 0.68 ; p = 0.03). The overall complications rate was 7.7%, most commonly wound dehiscence (2.7%), infections (0.9%), exposed hardware (2.0%), cerebrospinal fluid leaks (0.6%), and return to OR (3.8%). Patients who underwent index spinal wound reconstruction had a significantly lower complication rate (4.65%) than secondary spinal surgery patients (27.3%; p = 0.048). Conclusions The data confirmed significantly decreased complication rates for index back wound reconstructions for high-risk patients compared to delayed spine wound reconstruction. Increased rates of wound dehiscence, exposed hardware, and revisions occurred with delayed reconstruction. Early employment of tension free, robust vascular flap closure may attribute to a decreased complication profile.

Many expression quantitative trait loci (eQTL) studies have been conducted to investigate the biological effects of variants in gene regulation. However, these eQTL studies may suffer from low or moderate statistical power and overly conservative false-discovery rate. In practice, most algorithms for eQTL identification do not model the joint effects of multiple genetic variants with weak or moderate influence. Here we present a novel machine-learning algorithm, lasso least-squares kernel machine (LSKM-LASSO) that model the association between multiple genetic variants and phenotypic traits simultaneously with the existence of nongenetic and genetic confounding. With a more general and flexible framework for the estimation of genetic confounding, LSKM-LASSO is able to provide a more accurate evaluation of the joint effects of multiple genetic variants. Our simulations demonstrate that our approach outperforms three state-of-the-art alternatives in terms of eQTL identification and phenotype prediction. We then apply our method to genotype and gene expression data of 11 tissues obtained from the Genotype-Tissue Expression project. Our algorithm was able to identify more genes with eQTL than other algorithms. By incorporating a regularization term and combining it with least-squares kernel machine, LSKM-LASSO provides a powerful tool for eQTL mapping and phenotype prediction.

BACKGROUND Despite surgical correction of unilateral craniosynostosis (ULC), complex cranial base angulation can result in partial reversion to preoperative deformity with growth and time. Using 3-dimensional imaging, dysmorphic facial features of ULC in school-age patients were quantified and related to how they contribute to overall facial asymmetry and patient-reported outcomes. METHODS Children who underwent surgical correction of ULC were recruited from Yale University and Children's Hospital of Philadelphia. The 3D photographs were analyzed utilizing a Procrustes analysis of shape. Pearson's correlation was used to determine dysmorphic features' impact on overall asymmetry. Patients were stratified into "moderate" and "severe" asymmetry. Finally, asymmetry was correlated to patient-reported outcome scores. Statistical analysis was performed with SPSS-25 with P

BACKGROUND Reports of neurodevelopmental delays in adolescents with metopic craniosynostosis have ranged from 15 to 61 percent. Previously, event-related potentials have correlated preoperative radiographic severity with language deficiencies in infancy. This study sought to characterize neurocognitive testing at cranial maturity and correlate outcomes to preoperative radiographic severity. METHODS Patients diagnosed with metopic craniosynostosis who underwent surgical correction in infancy completed a neurodevelopmental battery evaluating age-normalized intelligence quotient, academic achievement, and visuomotor integration. Data were stratified by preoperative endocranial bifrontal angle (moderate, >124 degrees; severe