Early Intervention and Use of Autologous Grafts in Growing Skull Fractures Results in Better Outcomes: Experience From a Tertiary Pediatric Neurosurgery Center.

BACKGROUND AND OBJECTIVES: Growing skull fracture (GSF) is a rare complication of pediatric head trauma. Definitive treatment is surgical repair. We have attempted to assess whether use of autologous grafts for duraplasty and cranioplasty leads to better outcomes. We have also attempted to understand how timing of surgery might affect the degree of underlying damage to cortical tissue. METHODS: This is a single-center retrospective observational study based on review from the Great Ormond Street Hospital Neurosurgery prospective surgical database. All patients undergoing surgery for GSF repair between 1991 and 2015 were included. Surgical techniques included split calvarial grafts in 4 patients, whereas rest had full-thickness bone grafting. In all cases with full-thickness graft, the donor site was covered with morselized bone chips mixed with fibrin glue (Salami technique). RESULTS: Twenty-eight patients were identified (16 males, 12 females). The average age at the time of injury was 13 months. The mean duration of onset of symptoms from the time of injury was 4.4 months. The time interval from symptom onset to surgical repair was 5.92 months. Seven patients had Type I GSF (leptomeningeal cyst with minimal brain parenchyma), 13 had type II (hernia containing gliotic brain), and 8 had type III (porencephalic cyst extending through the skull defect into subgaleal space). Patients with delayed presentation had severe brain injury (Type III) and had more long-term complications (refractory epilepsy requiring temporo-occipito-parietal disconnection and development of hydrocephalus requiring ventriculoperitoneal shunt insertion). CONCLUSION: Autologous pericranium for duraplasty and split-thickness bone graft or the Salami technique are recommended for cranioplasty. Synthetic materials should be used if the index operation fails or there are complications. Patients with high-risk findings should be identified at the time of initial presentation and followed up in clinic early to prevent onset of neurological deficit. Early repair is associated with better neurological outcomes.

Outcomes following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies: 10 ​Year experience.

INTRODUCTION: The treatment of peritoneal malignancies has evolved and select patients can undergo effective surgical therapies. Access to innovative oncology procedures can be improved if programs are developed within and outside of academic cancer centers. We report the creation of a high volume, comprehensive peritoneal malignancy program developed in a community center. METHODS: A retrospective single-site study was conducted using registry data comprising all patients who underwent Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC) between October 2011-December 2021. RESULTS: 353 patients underwent CRS and HIPEC. 208 patients experienced in-hospital morbidity (58.9 â€‹%). Group comparison by disease site, PCI, and the completeness of cytoreduction demonstrated survival differences in mean overall survival and disease-free survival in 1-, 3- and 5-year ranges. CONCLUSIONS: This study demonstrates that with a standardized protocol and a surgeon-led multidisciplinary team it is possible to offer safe outcome driven, complex oncologic surgery in a community-based cancer program.

What can a morphometric study of unoperated children teach us about the natural history of metopic synostosis?

OBJECTIVE: Outcomes of surgical repair of trigonocephaly are well reported in the literature, but there is a paucity of information on the natural history of unoperated children. The authors evaluated a group of unoperated children with metopic synostosis to describe the natural change in head shape over time. METHODS: A database was screened for scans of children with unoperated trigonocephaly (2010-2021). Multisuture cases and those with a metopic ridge were excluded. Three-dimensional surface scans (3D stereophotogrammetry/CT) were used for morphological analysis. Nine previously published parameters were used: frontal angle (FA30°), anteroposterior (AP) volume ratio (APVR), AP area ratio (APAR), AP width ratios 1 and 2 (APWR1 and APWR2), and 4 AP diagonal ratios (30° right APDR [rAPDR30], 30° left APDR [lAPDR30], 60° right APDR [rAPDR60], and 60° left APDR [lAPDR60]). RESULTS: Ninety-seven scans were identified from a cohort of 316 patients with a single metopic suture, in which the male-to-female ratio was 2.7:1. Ages at the time of the scan ranged from 9 days to 11 years and were stratified into 4 groups: group 1, < 6 months; group 2, 6-12 months; group 3, 1-3 years; and group 4, > 3 years. Significant improvements were detected in 5 parameters (APVR, APAR, APWR1, rAPDR30, and lAPDR30) over time, whereas no significant differences were found in FA30, APWR2, rAPDR60, and lAPDR60 between age groups. CONCLUSIONS: Forehead shape (surface area and volume), as well as narrowing and anterolateral contour at the frontal points, differed significantly over time without surgery. However, forehead angulation, narrowing, and anterolateral contour at temporal points did not show significant differences. This knowledge will aid in surgical and parental decision-making.

Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.

AIMS: Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model. METHODS AND RESULTS: The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk. CONCLUSION: Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.

It is known that patients with chest pain without a recognized cause are at increased risk of future cardiovascular events (for example, heart disease) and so this study aimed to find out whether those patients at greatest risk could be determined using information in their health records. It is possible to accurately estimate a person's risk of future cardiovascular events using the information entered into their health records, and this risk can be estimated using only a small number of factors.Patients at highest risk could now be targeted for management to help prevent future cardiovascular events.

Frontofacial Surgery: Reducing Infection with the Development and 6-Year Outcome of a Frontofacial Protocol.

BACKGROUND: Frontofacial surgery (FFS) creates a communication between the cranial and nasal cavities and is associated with significant infection risk. After a cluster of infections affecting patients undergoing FFS, a root cause analysis of index cases was undertaken, but no specifically remedial causes were identified. Basic principles incorporating known risk factors for the prevention of surgical-site infection were then applied to the creation of a perioperative management protocol. This study analyzes infection rates before and after its implementation. METHODS: The protocol was designed around the needs of patients undergoing FFS and consists of three checklists covering their preoperative, intraoperative, and postoperative care. Compliance required the completion of each checklist. All patients undergoing FFS between 1999 and 2019 were studied retrospectively, and infections occurring before and after the implementation of the protocol were analyzed. RESULTS: One hundred three patients underwent FFS (60 monobloc and 36 facial bipartition) before the implementation of the protocol in August of 2013, and 30 patients underwent FFS after its implementation. Compliance with the protocol was 95%. After implementation, there was a statistically significant reduction in infections from 41.7% to 13.3% ( P = 0.005). CONCLUSIONS: Although no specific cause for a cluster of postoperative infection had been identified, the implementation of a bespoke protocol consisting of preoperative, perioperative, and postoperative checklists covering measures known to reduce infection risk was associated with a significant reduction in postoperative infections in patients undergoing FFS. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?

LEVEL OF EVIDENCE: III.

Sagittal synostosis: does choice of intervention and its timing affect the long-term aesthetic and neurodevelopmental outcome? A single-institution study of 167 children.

OBJECTIVE: Sagittal craniosynostosis (SC) is the most commonly encountered form of craniosynostosis. Despite its relative frequency, there remains significant heterogeneity in both operative management and follow-up between centers and a relative paucity of long-term outcome data in the literature. At the authors' institution, families of children presenting with SC are offered the following options: 1) conservative management with ophthalmic surveillance, 2) minimally invasive surgery at < 6 months of age (spring-assisted cranioplasty [SAC]) or 3) calvarial vault remodeling at any age (CVR). The authors reviewed outcomes for all children presenting with SC during a 5-year period, regardless of the treatment received. METHODS: Consecutive children born between January 1, 2008, and December 31, 2012, presenting with SC were identified, and detailed chart reviews were undertaken. Demographic, surgical, perioperative, head shape, scar, and neurodevelopmental (behavioral, education, speech, and language) data were analyzed. The cohort was divided by type of surgery (none, SAC, or CVR) and by age at surgery (early, defined as ≤ 6 months; or late, defined as > 6 months) for comparison purposes. RESULTS: A total of 167 children were identified, 129 boys and 38 girls, with a median age at presentation of 5.0 (range 0.4-135) months. Three families opted for conservative management. Of the 164 children who underwent surgery, 83 underwent SAC, 76 underwent CVR, and 5 underwent a "hybrid" procedure (CVR with springs). At a median age of 7.0 (range 0.5-12.3) years, there was no significant difference in concerns regarding head shape, scar, or neurodevelopmental outcomes between the early and late intervention groups over all procedures performed, or between the early or late SAC and CVR cohorts. There were more head shape concerns in the SAC group than in the CVR group overall (25.7% vs 11.8%, respectively; p = 0.026), although most of these concerns were minor and did not require revision. CONCLUSIONS: In this cohort, regardless of operative intervention and timing of intervention, infants achieved similar neurodevelopmental outcomes. Minimally invasive surgery (SAC) appears to result in less complete correction of head shape than CVR, but this may be balanced by advantages in reduced operative time, hospitalization, and blood loss. SAC was equal to CVR in neuropsychological outcomes.

Electrophysiological and fundoscopic detection of intracranial hypertension in craniosynostosis.

AIMS: To assess the diagnostic accuracy of fundoscopy and visual evoked potentials (VEPs) in detecting intracranial hypertension (IH) in patients with craniosynostosis undergoing spring-assisted posterior vault expansion (sPVE). METHODS: Children with craniosynostosis undergoing sPVE and 48-hour intracranial pressure (ICP) monitoring were included in this single-centre, retrospective, diagnostic accuracy study. Data for ICP, fundoscopy and VEPs were analysed. Primary outcome measures were papilloedema on fundoscopy, VEP assessments and IH, defined as mean ICP > 20 mmHg. Diagnostic indices were calculated for fundoscopy and VEPs against IH. Secondary outcome measures included final visual outcomes. RESULTS: Fundoscopic examinations were available for 35 children and isolated VEPs for 30 children, 22 of whom had at least three serial VEPs. Sensitivity was 32.1% for fundoscopy (95% confidence intervals [CI]: 15.9-52.4) and 58.3% for isolated VEPs (95% CI 36.6-77.9). Specificity for IH was 100% for fundoscopy (95% CI: 59.0-100) and 83.3% for isolated VEPs (95% CI: 35.9-99.6). Where longitudinal deterioration was suspected from some prVEPs but not corroborated by all, sensitivity increased to 70.6% (95% CI: 44.0-89.7), while specificity decreased to 60% (95% CI: 14.7-94.7). Where longitudinal deterioration was clinically significant, sensitivity decreased to 47.1% (23.0-72.2) and specificity increased to 100% (47.8-100). Median final BCVA was 0.24 logMAR (n = 36). UK driving standard BCVA was achieved by 26 patients (72.2%), defined as ≥0.30 logMAR in the better eye. CONCLUSION: Papilloedema present on fundoscopy reliably indicated IH, but its absence did not exclude IH. VEP testing boosted sensitivity at the expense of specificity, depending on method of analysis.

Does Hip Fracture Admitting Service Affect Proper Deep Venous Thrombosis Prophylaxis? An Investigation at a Level 1 Trauma Center.

OBJECTIVE: To examine if rates of appropriate thromboprophylaxis prescribing at the time of discharge would be higher in patients admitted to the orthopaedic service. Second, to see if improvements could be made in the rates of these missed events after a structured intervention. DESIGN: Retrospective Cohort Study, Prospective Interventional. SETTING: Level 1 Academic Hospital. PATIENTS: Two hundred forty-six patients undergoing a hip hemiarthroplasty for femoral neck fracture discharged to an extended care facility. INTERVENTION: A letter was sent to the internal quality control committee detailing our preintervention study. MAIN OUTCOME MEASURE: We looked at the differences among admitting services for missed thromboembolic prophylaxis (TPx) at the time of hospital discharge and rates of appropriate TPx after a structured intervention. RESULTS: No statistically significant differences existed in relation to patient age, gender, body mass index, or postoperative discharge day in the preintervention group. Orthopaedic surgery prescribed adequate TPx at discharge for 76 of 77 patients (98.7%), general trauma surgery for 26 of 30 patients (86.7%), and internal medicine for 85 of 96 patients (86.7%) in the preintervention group. There was a statistically significant difference when comparing adequate TPx between orthopaedic surgery and other services (P < 0.013 and <0.021, respectively). Our postintervention data found a significant decrease in the rates of missed TPx on discharge. In our preintervention sample group compared with our postintervention sample group, we saw a decrease in missed TPx of 5/39 versus 0/43 events (P = 0.021). CONCLUSIONS: We found that a letter sent to all members of a hospital internal quality committee decreased incidences of missed TPx. Specifically, this letter explained the details of our study that kept track of rates of missed TPx among different admitting services. We found that after our intervention, which consisted of a letter and a multidisciplinary discussion, the rate of missed thromboembolic prophylaxis events improved from 5/39 (12%) to 0/43 (0%) (P = 0.021). LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Activity of Cabazitaxel in Metastatic or Inoperable Locally Advanced Dedifferentiated Liposarcoma: A Phase 2 Study of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG).

Importance: Treatment options for patients with unresectable and/or metastatic dedifferentiated liposarcoma (DDLPS) are limited. New drugs are required. Objective: To assess whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DDLPS to justify further investigation in a phase 3 setting. Design, Setting, and Participants: This international multicenter, open-label single-arm phase 2 trial was conducted at 10 institutions in 4 European countries from March 2015 to March 2019. Eligible patients had to have metastatic or locally advanced histologically proven DDLPS with evidence of disease progression within the past 6 months and had to have received no more than 1 previous line of chemotherapy. Interventions: After mandatory central review of tumor blocks, if the DDLPS diagnosis was confirmed, patients started treatment within 72 hours after registration. Cabazitaxel was administered at a dose of 25 mg/m2 IV infusion over 1 hour every 21 days until intolerance, progression, or withdrawal of consent. Main Outcomes and Measures: The primary end point was progression-free survival (PFS) rate at 12 weeks per RECIST 1.1. Based on a Simon 2-stage design, at least 4 of 17 (stage 1) and 11 of 37 (stage 2) eligible and evaluable patients who were progression free at 12 weeks were needed. The final analysis report was completed on November 17, 2021. Results: Forty patients were registered, with 2 patients being ineligible. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. Progression-free survival at 12 weeks was 55%, achieving the primary study end point. At a median follow-up of 21.6 months, median PFS was 6 months and median OS 21 months. Response rate (RR) was 8% with 1 clinical response (CR) and 2 partial responses (PR). Twenty-three (60.5%) patients had a stable disease (SD). Disease control (PR+SD) was achieved in 26 patients (68%). Conclusions and Relevance: This nonrandomized phase 2 clinical trial met its primary end point, with 21 of 38 patients (55%) being progression free at 12 weeks. These results suggest important activity of cabazitaxel in patients with metastatic or inoperable locally advanced DDLPS. The drug is worth being further studied in these tumors in a phase 3 setting.

Endoscopic strip craniectomy with molding helmet therapy versus spring-assisted cranioplasty for nonsyndromic single-suture sagittal craniosynostosis: a systematic review.

OBJECTIVE: Endoscopic strip craniectomy with postoperative molding helmet therapy (ESC-H) and spring-assisted cranioplasty (SAC) are commonly used minimally invasive techniques for correction of nonsyndromic sagittal craniosynostosis, but it is unclear which, if either, is superior. Therefore, the authors undertook a systematic review to compare ESC-H with SAC for the surgical management of nonsyndromic single-suture sagittal craniosynostosis. METHODS: Studies were identified through a systematic and comprehensive search of four databases (Embase, MEDLINE, and two databases in the Cochrane Library). Databases were searched from inception until February 19, 2021. Pediatric patients undergoing either ESC-H or SAC for the management of nonsyndromic single-suture sagittal craniosynostosis were included. Systematic reviews and meta-analyses, single-patient case reports, mixed cohorts of nonsyndromic and syndromic patients, mixed cohorts of different craniosynostosis types, and studies in which no outcomes of interest were reported were excluded. Outcomes of interest included reoperations, blood transfusion, complications, postoperative intensive care unit (ICU) admission, operative time, estimated blood loss, length of hospital stay, and cephalic index. Pooled summary cohort characteristics were calculated for each outcome of interest. Methodological quality was assessed using the Newcastle-Ottawa Scale. The study was reported in accordance with the 2020 PRISMA statement. RESULTS: Twenty-two studies were eligible for inclusion in the review, including 1094 patients, of whom 605 (55.3%) underwent ESC-H and 489 (44.7%) underwent SAC for nonsyndromic sagittal craniosynostosis. There was no difference between the pooled estimates of the ESC-H and SAC groups for operative time, length of stay, estimated blood loss, and cephalic index. There was no difference between the groups for reoperation rate and complication rate. However, ESC-H was associated with a higher blood transfusion rate and higher postoperative ICU admission. CONCLUSIONS: The available literature does not demonstrate superiority of either ESC-H or SAC, and outcomes are broadly similar for the treatment of nonsyndromic sagittal craniosynostosis. However, the evidence is limited by single-center retrospective studies with low methodological quality. There is a need for international multicenter randomized controlled trials comparing both techniques to gain definitive and generalizable data.

Collateral-resistance to estrogen and HER-activated growth is associated with modified AKT, ERα, and cell-cycle signaling in a breast cancer model.

Aim: A model of progressively endocrine-resistant breast cancer was investigated to identify changes that can occur in signaling pathways after endocrine manipulation. Methods: The MCF7 breast cancer model is sensitive to estrogens and anti-estrogens while variant lines previously derived from wild-type MCF7 are either relatively 17ß-estradiol (E2)-insensitive (LCC1) or fully resistant to estrogen and anti-estrogens (LCC9). Results: In LCC1 and LCC9 cell lines, loss of estrogen sensitivity was accompanied by loss of growth response to transforming growth factor alpha (TGFα), heregulin-beta and pertuzumab. LCC1 and LCC9 cells had enhanced AKT phosphorylation relative to MCF7 which was reflected in downstream activation of phospho-mechanistic target of rapamycin (mTOR), phospho-S6, and phospho-estrogen receptor alpha Ser167 [ERα(Ser167)]. Both AKT2 and AKT3 were phosphorylated in the resistant cell lines, but small interfering RNA (siRNA) knockdown suggested that all three AKT isoforms contributed to growth response. ERα(Ser118) phosphorylation was increased by E2 and TGFα in MCF7, by E2 only in LCC1, but by neither in LCC9 cells. Multiple alterations in E2-mediated cell cycle control were identified in the endocrine-resistant cell lines including increased expression of MYC, cyclin A1, cyclin D1, cyclin-dependent kinase 1 (CDK1), CDK2, and hyperphosphorylated retinoblastoma protein (ppRb), whereas p21 and p27 were reduced. Estrogen modulated expression of these regulators in MCF7 and LCC1 cells but not in LCC9 cells. Seliciclib inhibited CDK2 activation in MCF7 cells but not in resistant variants; in all lines, it reduced ppRb, increased p53 associated responses including p21, p53 up-regulated modulator of apoptosis (PUMA), and p53 apoptosis-inducing protein 1 (p53AIP1), inhibited growth, and produced G2/M block and apoptosis. Conclusions: Multiple changes occur with progression of endocrine resistance in this model with AKT activation contributing to E2 insensitivity and loss of ERα(Ser118) phosphorylation being associated with full resistance. Cell cycle regulation is modified in endocrine-resistant breast cancer cells, and seliciclib is effective in both endocrine-sensitive and resistant diseases.

Estimated Cost of Transcarotid Arterial Revascularization Compared With Carotid Endarterectomy and Transfemoral Carotid Stenting.

Objectives Transcarotid arterial revascularization (TCAR) is associated with a lower risk of stroke or death than transfemoral carotid artery stenting (TF-CAS). TCAR infers a lower risk of cranial nerve injury and a similar risk of myocardial infarction (MI) than carotid endarterectomy (CEA). There have been no comparative studies on the cost of TCAR, TF-CAS, and CEA, which may have important implications for institutional support for the new modality to address carotid artery stenosis. Our aim was to compare the estimated cost profiles of TCAR, TF-CAS, and CEA. Methods A review was performed on Medicare patients who underwent TCAR, TF-CAS, or CEA between January 1, 2020, and December 31, 2020. Demographics, comorbidities, operative details, and postoperative complications were reviewed. Acute stroke presentations and elective procedures were included. Cost data were obtained from the hospital's finance department. Quantitative variables were compared using analysis of variance, and categorical variables were compared using the chi-square analysis. Results In total, 21 TCAR, 97 TF-CAS, and 26 CEA patients were initially identified. After removing the non-Medicare patients, 17 TCAR, 57 TF-CAS, and 13 CEA patients were included in the analysis. In-hospital stroke, MI, and mortality included three deaths in TF-CAS patients. At 30 days, the stroke rates for TCAR, TF-CAS, and CEA groups were 0%, 1.8%, and 0%, respectively. The payments for TCAR, TF-CAS, and CEA were $15,400 ± 2,100, $23,400 ± 11,800 and $14,300 ± 5,700 (p=0.001), respectively. The estimated costs for TCAR, TF-CAS, and CEA were $10,500 ± 3,300, $13,800 ± 14,300, and $12,400 ± 6,000 (p=0.575), respectively. The profit margins for TCAR, TF-CAS, and CEA were $5,100 ± 3,100, $9,600 ± 12,100, and $1,900 ± 6,400 (p=0.032), respectively. There was no significant difference in American Society of Anesthesiologists (ASA) scores (p=0.635) or age (p=0.485) among the three groups. The length of hospital stay was not significantly different (p=0.107). The TF-CAS maintained the highest profit margin (p<0.001) when matched for the same diagnosis-related code (without complications or comorbidities). Urgency classification within the TF-CAS group included 45 elective, four urgent, and eight emergent cases. The profit margin was significantly higher for the elective group than for the emergent group (p=0.002) but not different for elective versus urgent (p=0.503) or urgent versus emergent (p=0.102). All patients who underwent TCAR and CEA were elective. Conclusion The hospital reimbursement and profit margins are higher for TF-CAS than for TCAR. With the increasing data now demonstrating similar outcomes with TF-CAS and CEA, further research is required to examine the long-term cost-effectiveness of TCAR and how this will compare to TF-CAS.

Long-Term Cardiovascular Risk and Management of Patients Recorded in Primary Care With Unattributed Chest Pain: An Electronic Health Record Study.

Background Most adults presenting with chest pain will not receive a diagnosis and be recorded with unattributed chest pain. The objective was to assess if they have increased risk of cardiovascular disease compared with those with noncoronary chest pain and determine whether investigations and interventions are targeted at those at highest risk. Methods and Results We used records from general practices in England linked to hospitalization and mortality information. The study population included patients aged 18 years or over with a new record of chest pain with a noncoronary cause or unattributed between 2002 and 2018, and no cardiovascular disease recorded up to 6 months (diagnostic window) afterward. We compared risk of a future cardiovascular event by type of chest pain, adjusting for cardiovascular risk factors and alternative explanations for chest pain. We determined prevalence of cardiac diagnostic investigations and preventative medication during the diagnostic window in patients with estimated cardiovascular risk ≥10%. There were 375 240 patients with unattributed chest pain (245 329 noncoronary chest pain). There was an increased risk of cardiovascular events for patients with unattributed chest pain, highest in the first year (hazard ratio, 1.25 [95% CI, 1.21-1.29]), persistent up to 10 years. Patients with unattributed chest pain had consistently increased risk of myocardial infarction over time but no increased risk of stroke. Thirty percent of patients at higher risk were prescribed lipid-lowering medication. Conclusions Patients presenting to primary care with unattributed chest pain are at increased risk of cardiovascular events. Primary prevention to reduce cardiovascular events appears suboptimal in those at higher risk.

Late Deformity Following Fronto-Orbital Reconstructive Surgery for Metopic Synostosis: The Role of Temporalis Muscle.

ABSTRACT: Theories for late-developing deformity (LDD) following fronto-orbital reconstructive surgery (FOR) for metopic synostosis (MS) must explain both its delayed onset and its physical characteristics. This study examined whether FOR-related interference with the normal childhood expansion of temporalis is responsible for its soft tissue component.Three-dimensional reformats of preoperative and postoperative computed tomography scans of MS patients were reviewed. Measurements of vertical and horizontal reach of temporalis against those of the underlying skull (to allow for normal skull growth) were compared with normal subjects. The thickness of temporalis and the development of the temporal crests were also assessed.Mean age at FOR was 17.1 months; interval between surgery and first report of LDD 4.7 years; mean age at computed tomography scan for post-FOR LDD patients 8.8 years. There was a significant difference between vertical and horizontal reach of temporalis in pre-FOR MS patients compared to normal subjects ( P < 0.0017 and P < 0.05, respectively). The vertical age-related reach of temporalis in post-FOR patients after allowing for underlying skull growth was significantly reduced ( P = 0.0045) compared to normal subjects but not its horizontal reach ( P = 0.25). Temporal crests in LDD patients were absent or aberrantly formed while muscle thickness was similar to normal subjects at the 2 levels measured.This study supports the theory that failure of the normal childhood expansion of temporalis is responsible for the soft tissue element of LDD, accounting for both its delayed onset and physical characteristics. Aberrant temporal crest development suggests FOR-related damage as the probable cause.

Spring-assisted posterior vault expansion-a single-centre experience of 200 cases.

PURPOSE: Children affected by premature fusion of the cranial sutures due to craniosynostosis can present with raised intracranial pressure and (turri)brachycephalic head shapes that require surgical treatment. Spring-assisted posterior vault expansion (SA-PVE) is the surgical technique of choice at Great Ormond Street Hospital for Children (GOSH), London, UK. This study aims to report the SA-PVE clinical experience of GOSH to date. METHODS: A retrospective review was carried out including all SA-PVE cases performed at GOSH between 2008 and 2020. Demographic and clinical data were recorded including genetic diagnosis, craniofacial surgical history, surgical indication and assessment, age at time of surgery (spring insertion and removal), operative time, in-patient stay, blood transfusion requirements, additional/secondary (cranio)facial procedures, and complications. RESULTS: Between 2008 and 2020, 200 SA-PVEs were undertaken in 184 patients (61% male). The study population consisted of patients affected by syndromic (65%) and non-syndromic disorders. Concerns regarding raised intracranial pressure were the surgical driver in 75% of the cases, with the remainder operated for shape correction. Median age for SA-PVE was 19 months (range, 2-131). Average operative time for first SA-PVE was 150 min and 87 for spring removal. Median in-patient stay was 3 nights, and 88 patients received a mean of 204.4 ml of blood transfusion at time of spring insertion. A single SA-PVE sufficed in 156 patients (85%) to date (26 springs still in situ at time of this analysis); 16 patients underwent repeat SA-PVE, whilst 12 underwent rigid redo. A second SA-PVE was needed in significantly more cases when the first SA-PVE was performed before age 1 year. Complications occurred in 26 patients with a total of 32 events, including one death. Forty-one patients underwent fronto-orbital remodelling at spring removal and 22 required additional cranio(maxillo)facial procedures. CONCLUSIONS: Spring-assisted posterior vault expansion is a safe, efficient, and effective procedure based on our 12-year experience. Those that are treated early in life might require a repeat SA-PVE. Long-term follow-up is recommended as some would require additional craniomaxillofacial correction later in life.

Chlamydia Uses K+ Electrical Signalling to Orchestrate Host Sensing, Inter-Bacterial Communication and Differentiation.

Prokaryotic communities coordinate quorum behaviour in response to external stimuli to control fundamental processes including inter-bacterial communication. The obligate intracellular bacterial pathogen Chlamydia adopts two developmental forms, invasive elementary bodies (EBs) and replicative reticulate bodies (RBs), which reside within a specialised membrane-bound compartment within the host cell termed an inclusion. The mechanisms by which this bacterial community orchestrates different stages of development from within the inclusion in coordination with the host remain elusive. Both prokaryotic and eukaryotic kingdoms exploit ion-based electrical signalling for fast intercellular communication. Here we demonstrate that RBs specifically accumulate potassium (K+) ions, generating a gradient. Disruption of this gradient using ionophores or an ion-channel inhibitor stalls the Chlamydia lifecycle, inducing persistence. Using photobleaching approaches, we establish that the RB is the master regulator of this [K+] differential and observe a fast K+ exchange between RBs revealing a role for this ion in inter-bacterial communication. Finally, we demonstrate spatio-temporal regulation of bacterial membrane potential during RB to EB differentiation within the inclusion. Together, our data reveal that Chlamydia harnesses K+ to orchestrate host sensing, inter-bacteria communication and pathogen differentiation.