High-intensity interval training programme for obese youth (HIP4YOUTH): A pilot feasibility study.

Recently, there has been growing interest in high-intensity interval training (HIT) as a strategy to improve health. In this pilot study, we examined the feasibility of a 4-week low-volume HIT and its effects on cardiorespiratory fitness (CRF), blood pressure (BP) and enjoyment in overweight and obese youth. Twelve adolescents (body mass index (BMI): 34.8 ± 3.9 kg · m‒2, 14.9 ± 1.5 years) participated in 12 sessions of HIT (10 × 60 s cycling bouts eliciting ~90% maximal heart rate, interspersed with 90 s recovery, 30 min/session, 3 sessions/week) over ~4 weeks. All the participants completed the study and exercise attendance averaged 92%. Despite no changes in body weight and total fat, HIT resulted in significant (P < 0.01) increases in CRF (pre: 20.1 versus post: 22.2 ml · kg‒1 · min‒1) and exercise time (pre: 425 versus post: 509 s) during peak oxygen uptake test, and a reduction in resting systolic BP (pre: 115.8 versus post: 107.6 mmHg). The majority of study participants (83%) enjoyed HIT and more than half of the participants (58%) reported that HIT is a more enjoyable form of exercise compared to other types of exercises. Low-volume HIT is a useful strategy to promote exercise participation and improve cardiovascular health in overweight and obese youth.

The Regional Autopsy Center: The University of Alabama at Birmingham Experience.

Rates of autopsied deaths have decreased significantly for the last several decades. It may not be practical for some institutions to maintain the facilities and staffing required to perform autopsies. In recent years, the University of Alabama at Birmingham (UAB) has established contracts to perform autopsies for several regional institutions including the Alabama Department of Forensic Sciences (ADFS), the United States Veterans Affairs, the local prison system, local community hospitals, and with families for private autopsy services. Contracts and autopsy data from 2004 to 2015 were obtained and reviewed. Since 2004, the number of UAB hospital autopsies trended slightly downward. On average, UAB hospital cases comprised most yearly cases, and the ADFS was the second largest contributor of cases. Income generated from outside autopsies performed from 2006 to 2015 totaled just more than 2 million dollars, and most of the income was generated from referred ADFS cases. This study provides evidence that a centralized institution (regional autopsy center [RAC]) can provide regional autopsy service in a practical, feasible, and economically viable manner, and a RAC can benefit both the referring institutions as well as the RAC itself.

Histological characteristics of the fetal inflammatory response associated with neurodevelopmental impairment and death in extremely preterm infants.

OBJECTIVE: To test the hypothesis that increasing severity of the fetal inflammatory response (FIR) would have a dose-dependent relationship with severe neurodevelopmental impairment or death in extremely preterm infants. STUDY DESIGN: We report 347 infants of 23-28 weeks gestational age admitted to a tertiary neonatal intensive care unit between 2006 and 2008. The primary outcome was death or neurodevelopmental impairment at the 18- to 22-month follow-up. Exposure status was defined by increasing stage of funisitis (stage 1, phlebitis; stage 2, arteritis with or without phlebitis; stage 3, subacute necrotizing funisitis) and severity of chorionic plate vasculitis (inflammation with or without thrombosis). RESULTS: A FIR was detected in 110 placentas (32%). The rate of severe neurodevelopmental impairment/death was higher in infants with subacute necrotizing funisitis compared with infants without placental/umbilical cord inflammation (60% vs 35%; P < .05). Among infants with stage 1 or 2 funisitis, the presence of any chorionic vasculitis was associated with a higher rate of severe neurodevelopmental impairment/death (47% vs 23%; P < .05). After adjustment for confounding factors, only subacute necrotizing funisitis (risk ratio, 1.87; 95% CI, 1.04-3.35; P = .04) and chorionic plate vasculitis with thrombosis (risk ratio, 2.21; 95% CI, 1.10-4.46; P = .03) were associated with severe neurodevelopmental impairment/death. CONCLUSION: Severe FIR, characterized by subacute necrotizing funisitis and severe chorionic plate vasculitis with thrombosis, is associated with severe neurodevelopmental impairment/death in preterm infants.

Multi-disciplinary, simulation-based, standardised trauma team training within the Victorian State Trauma System.

OBJECTIVE: Inconsistency in the structure and function of team-based major trauma reception and resuscitation is common. A standardised trauma team training programme was initiated to improve quality and consistency among trauma teams across a large, mature trauma system. The aim of this manuscript is to outline the programme and report on the initial perception of participants. METHODS: The Alfred Trauma Team Reception and Resuscitation Training (TTRRT) programme commenced in March 2019. Participants included critical care and surgical craft group members commonly involved in trauma teams. Training was site-specific and included rural, urban and tertiary referral centres. The programme consisted of prescribed pre-learning, didactic lectures, skill stations and simulated team-based scenarios. Participant perceptions of the programme were collected before and after the programme for analysis. RESULTS: The TTRRT was delivered to 252 participants and 120 responses were received. Significant improvement in participant-reported confidence was identified across all key topic areas. There was also a significant increase in both confidence and clinical exposure to trauma team leadership roles after participation in the programme (from 53 [44.2%] to 74 [61.7%; P = 0.007]). This finding was independent of clinician experience. CONCLUSIONS: A team-based trauma reception and resuscitation education programme, introduced in a large, mature trauma system led to positive participant-reported outcomes in clinical confidence and real-life team leadership participation. Wider implementation combined with longitudinal data collection will facilitate correlation with patient and staff-centred outcomes.

The C134W (402 C>G) FOXL2 mutation is absent in ovarian gynandroblastoma: insights into the genesis of an unusual tumour.

AIMS: Ovarian gynandroblastomas are rare tumours that, by definition, comprise a combination of components resembling both female, typically granulosa cell tumour (GCT), and male, typically Sertoli or Sertoli/Leydig cell tumour (ST/SLT), sex cord/stromal differentiation. The histogenesis of these tumours is unknown and, in view of the very strong association between the C134W (402 C>G) FOXL2 mutation and adult-type GCT, we analysed a series of gynandroblastomas for this mutation. METHODS AND RESULTS: Both components of each lesion were isolated by laser capture microdissection and the C134W (402 C>G) FOXL2 mutation was analysed by polymerase chain reaction sequencing. No mutation was identified in either the GCT or ST/SLT component of six cases, three of which contained adult-type GCT. CONCLUSIONS: This suggests that, despite their similar morphological appearances, the GCT-like component of gynandroblastoma has a different molecular basis from conventional adult-type GCT. This finding underscores a more general principle that morphological similarity does not necessarily indicate molecular identity.

Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of sinus of valsalva aneurysm rupture.

We present an adult patient with rupture of the right sinus of Valsalva aneurysm in whom the two-dimensional transesophageal echocardiogram failed to show the rupture. On the other hand, live/real time three-dimensional transesophageal echocardiography clearly delineated the site of rupture into the pericardium and mediastinum.

A Postmortem Portrait of the Coronavirus Disease 2019 (COVID-19) Pandemic: A Large Multi-institutional Autopsy Survey Study.

CONTEXT.­: This study represents the largest compilation to date of clinical and postmortem data from decedents with coronavirus disease 2019 (COVID-19). It will augment previously published small series of autopsy case reports, refine clinicopathologic considerations, and improve the accuracy of future vital statistical reporting. OBJECTIVE.­: To accurately reflect the preexisting diseases and pathologic conditions of decedents with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection through autopsy. DESIGN.­: Comprehensive data from 135 autopsy evaluations of COVID-19-positive decedents is presented, including histologic assessment. Postmortem examinations were performed by 36 pathologists at 19 medical centers or forensic institutions in the United States and Brazil. Data from each autopsy were collected through the online submission of multiple-choice and open-ended survey responses. RESULTS.­: Patients dying of or with COVID-19 had an average of 8.89 pathologic conditions documented at autopsy, spanning a combination of prior chronic disease and acute conditions acquired during hospitalization. Virtually all decedents were cited as having more than 1 preexisting condition, encompassing an average of 2.88 such diseases each. Clinical conditions during terminal hospitalization were cited 395 times for the 135 autopsied decedents and predominantly encompassed acute failure of multiple organ systems and/or impaired coagulation. Myocarditis was rarely cited. CONCLUSIONS.­: Cause-of-death statements in both autopsy reports and death certificates may not encompass the severity or spectrum of comorbid conditions in those dying of or with COVID-19. If supported by additional research, this finding may have implications for public health decisions and reporting moving forward through the pandemic.

The World Health Organization trauma checklist versus Trauma Team Time-out: A perspective.

Time-out protocols have reportedly improved team dynamics and patients' safety in various clinical settings - particularly in the operating room. In 2016, the World Health Organization (WHO) introduced a Trauma Care checklist, which outlines steps to follow immediately after the primary and secondary surveys and prior to the team leaving the patient. The WHO Trauma Care checklist's main perceived benefit is the prompting of clinicians to complete trauma admissions as per evidence-based guidelines. The WHO Trauma Care checklist, while likely to be successful in reducing errors of omission related to hospital admission, may be limited in its ability to reduce errors that occur in the initial 30 min of trauma reception - when most of the life-saving decisions are made. To address this limitation a Trauma Team Time-out protocol is proposed for initial trauma resuscitation, targeting the critical first 30 min of hospital reception.

Statins improve human coronary atherosclerotic plaque morphology.

Statin treatment markedly reduces the incidence of acute coronary events in patients with coronary atherosclerosis. Although imaging studies have indirectly shown the beneficial effects of statins on plaque morphology, there has to our knowledge been no reported histologic comparison of the morphology of coronary plaque in statin-treated versus untreated patients who had substantial coronary artery atherosclerosis. We retrospectively studied arterial sections from the native hearts of patients who had experienced end-stage ischemic heart disease and subsequent cardiac transplantation. Of 44 qualified patients, 33 study patients had received pre-transplantation statin therapy, and 11 control patients had not. Pathologic examination of each explanted heart confirmed coronary artery disease and previous myocardial infarction in all patients. Diabetes mellitus was more prevalent in the study group. The groups were similar in levels of total and low-density lipoprotein cholesterol, and in the available number of arterial cross-sections per patient. All patients had plaques. High-grade lesions were found in 66.3% of cross-sections in the control group, and in 34.6% in the study group (P=0.011). Conversely, the degree of inflammation was markedly lower in the study group: low-grade fibrous plaques occurred in 45.7% of cross-sections in the study group, versus 11.3% in the control group (P=0.006). The study group had significantly fewer high-grade plaques and more fibrous plaques than did the control group at the time of transplantation. Our findings show that statin therapy substantially enhances plaque stabilization. We further suggest that reduction of plaque inflammation is an important aspect of this stabilization.

Clinical features and outcomes of pregnancies complicated by pre-ecplampsia necessitating in-utero transfer.

OBJECTIVES: Pre-eclampsia (PE) is associated with significant risks of adverse perinatal outcomes, often necessitating transfer to a higher level of care for specialist perinatal management. In Victoria, Australia, the Paediatric Infant Perinatal Emergency Retrieval (PIPER) coordinates in-utero transfers of high-risk pregnancies. Our objectives were to report the clinical features and outcomes of women referred to PIPER with a primary diagnosis of PE, and subsequently transferred in-utero. STUDY DESIGN: A retrospective audit of consecutive pregnancies referred to PIPER in 2013-2014 with a primary diagnosis of pre-eclampsia, ≥20 weeks' gestation and transferred in-utero. MAIN OUTCOME MEASURES: Severity of disease, gestational age, transfer details and outcome until 7 days post transfer. RESULTS: Over two years, 244 women were referred to PIPER with PE; 199 (82%) were subsequently transferred in-utero. Severe PE was diagnosed in 146 (73%) women. Overall, 64% presented 'early' (<32 weeks' gestation). Only 6% were ≥37 weeks. All but 2 women <32 weeks were transferred to a tertiary perinatal centre, compared with 39% of women ≥32 weeks. Within 7 days, 153/199 (77%) delivered, 10% remained in-patients and 12.5% were discharged. There were 165 livebirths and 3 stillbirths, with a mean gestational age of 30.7 weeks (SD 3.3 weeks). Twenty-nine women required high dependency or intensive care admission. No maternal deaths were reported. CONCLUSION: Women referred to PIPER predominantly presented with early onset, severe PE and most delivered within 7 days of transfer. Data from this study provides important information for obstetric service planning in Victoria and comparable regions.

The Value of Outsourcing Selected Cases in a Medical Examiner Population: A 10-Year Experience.

Due to increasing caseloads and inadequate staffing, the burden on Coroner/Medical Examiner Offices to comply with recommended autopsy limits for forensic pathologists (FPs) has been difficult. Since 2006, pathologists at the University of Alabama at Birmingham have performed select autopsies for the Alabama Department of Forensic Sciences. Each case was reviewed by a state FP and scene investigator to determine appropriateness for referral. All referred cases received full postmortem examination including microscopic examination and collection of toxicological samples, and toxicology was ordered by the referring FP as appropriate. The final cause and manner of death were determined by the referring state FP after review of all findings. A majority of the 421 cases were ruled accidental deaths (233), most due to drug toxicity. Of the 178 natural deaths, 118 were attributed to cardiovascular disease. Outsourcing select forensic cases can be educational and an effective tool to manage workflow without compromising quality.

Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.

Anterior Gradient Protein (AGR-2) is reported to be over-expressed in many epithelial cancers and promotes metastasis. A clear-cut mechanism for its observed function(s) has not been previously identified. We found significant upregulation of AGR-2 expression in a bone metastatic prostate cancer cell line, PC3, following culturing in bone marrow-conditioned medium. Substantial AGR-2 expression was also confirmed in prostate cancer tissue specimens in patients with bone lesions. By developing stable clones of PC3 cells with varying levels of AGR-2 expression, we identified that abrogation of AGR-2 significantly reduced cellular attachment to fibronectin, collagen I, collagen IV, laminin I and fibrinogen. Loss of cellular adhesion was associated with sharp decrease in the expression of α4, α5, αV, ß3 and ß4 integrins. Failure to undergo apoptosis following detachment is a hallmark of epithelial cancer metastasis. The AGR-2-silenced PC3 cells showed higher resistance to Tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) induced apoptosis in vitro. This observation was also supported by significantly reduced Caspase-3 expression in AGR-2-silenced PC3 cells, which is a key effector of both extrinsic and intrinsic death signaling pathways. These data suggest that AGR-2 influence prostate cancer metastasis by regulation of cellular adhesion and apoptosis.

Clostridium septicum aortitis causing aortic dissection in a 22-year-old man.

Clostridium septicum infection is a rare cause of aortic dissection, and the mortality rate for the condition is high. Only 26 cases of C. septicum aortitis have been reported; all of those patients were elderly, and 20 of them had an associated colonic neoplasm. Herein, we present the case of a 22-year-old man whose C. septicum aortitis resulted in aortic dissection that involved the entire length of the aorta. Upon autopsy, no neoplasm or other predisposing condition was identified in this patient. To the best of our knowledge, this is the 1st report of C. septicum aortitis, fatal or otherwise, in a young individual.