What’s old is new again: The sacroiliac joint as a cause of lateralizing low back pain

It has not been easy to identify mechanical failure of the sacroiliac joint (SIJ) with traditional imaging. The integrated model of function (Lee and Vleeming, 1998) suggests that under normal circumstances, form and force closure combined contribute to sacral nutation and “locking” the SIJ for optimal load transfer. This model is supported by clinical evidence and scintigraphic findings that contribute to successful therapy in 80% of cases. Single-photon emission computed tomography and x-ray computed tomography (SPECT-CT), a hybrid device, was used in a study of 1200 patients (64% female and 36% male patients with an average age of 42 years; range, 15–78 years) with a clinical diagnosis of SIJ incompetence (pelvic girdle pain syndrome). Standard clinical testing and an alternate series of tests were used as a reference standard for imaging. Symptoms were present for a mean of 43 months. Imaging finding were of increased uptake in the upper SIJ (S1–S2), with extension into the dorsal interosseous ligament and measurable by count profile. Associated findings of tendon enthesopathy reflected altered biomechanics around the pelvis. Ipsilateral adductor enthesopathy was found in 70% and contralateral hamstring enthesopathy in 60% of patients. SPECT-CT criteria for the diagnosis of SIJ incompetence were developed and validated. SPECT-CT is a valid and reproducible technique for the diagnosis of SIJ incompetence with high concordance and specificity compared to the reference standards. Findings are supportive of the integrated model of SIJ function proposed by Lee and Vleeming

Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy

AbstractOBJECTIVESWe performed positron emission tomography (PET) to evaluate myocardial ischemia in patients with idiopathic dilated cardiomyopathy (IDC).BACKGROUNDPatients with IDC have anatomically normal coronary arteries, and it has been assumed that myocardial ischemia does not occur.METHODSWe studied 22 patients with IDC and 22 control subjects using PET with nitrogen-13 ammonia to measure myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia. To investigate glucose metabolism, fluorine-18 deoxyglucose (18FDG) was used. For imaging of oxygen consumption, carbon-11 acetate clearance rate constants (kmono) were assessed at rest and during submaximal dobutamine infusion (20 μg/kg body weight per min).RESULTSGlobal MBF reserve (dipyridamole-induced) was impaired in patients with IDC versus control subjects (1.7 ± 0.21 vs. 2.7 ± 0.10, p < 0.05). In patients with IDC, MBF reserve correlated with left ventricular (LV) systolic wall stress (r = −0.61, p = 0.01). Furthermore, in 16 of 22 patients with IDC (derived by dipyridamole perfusion) mismatch (decreased flow/increased 18FDG uptake) was observed in 17 ± 8% of the myocardium. The extent of mismatch correlated with LV systolic wall stress (r = 0.64, p = 0.02). The MBF reserve was lower in the mismatch regions than in the normal regions (1.58 ± 0.13 vs. 1.90 ± 0.18, p < 0.05). During dobutamine infusion kmonowas higher in the mismatch regions than in the normal regions (0.104 ± 0.017 vs. 0.087 ± 0.016 min−1, p < 0.05). In the mismatch regions 18FDG uptake correlated negatively with rest kmono(r = −0.65, p < 0.05), suggesting a switch from aerobic to anaerobic metabolism.CONCLUSIONSPatients with IDC have a decreased MBF reserve. In addition, low MBF reserve was paralleled by high LV systolic wall stress. These global observations were associated with substantial myocardial mismatch areas showing the lowest MBF reserves. In geographically identical regions an abnormal oxygen consumption pattern was seen together with a switch from aerobic to anaerobic metabolism. These data support the notion that regional myocardial ischemia plays a role in IDC

Reduced Left Ventricular Torsion Early After Myocardial Infarction Is Related to Left Ventricular Remodeling

Background— Left ventricular (LV) torsion is emerging as a sensitive parameter of LV systolic myocardial performance. The aim of the present study was to explore the effects of acute myocardial infarction (AMI) on LV torsion and to determine the value of LV torsion early after AMI in predicting LV remodeling at 6-month follow-up. Methods and Results— A total of 120 patients with a first ST-segment elevation AMI (mean±SD age, 59±10 years; 73% male) were included. All patients underwent primary percutaneous coronary intervention. After 48 hours, speckle-tracking echocardiography was performed to assess LV torsion; infarct size was assessed by myocardial contrast echocardiography. At 6-month follow-up, LV volumes and LV ejection fraction were reassessed to identity patients with LV remodeling (defined as a ≥15% increase in LV end-systolic volume). Compared with control subjects, peak LV torsion in AMI patients was significantly impaired (1.54±0.64°/cm vs 2.07±0.27°/cm, P <0.001). By multivariate analysis, only LV ejection fraction ( β =0.36, P <0.001) and infarct size ( β =−0.47, P <0.001) were independently associated with peak LV torsion. At 6-month follow-up, 19 patients showed LV remodeling. By multivariate analysis, only peak LV torsion (odds ratio=0.77; 95% CI, 0.65–0.92; P =0.003) and infarct size (odds ratio=1.04; 95% CI, 1.01–1.07; P =0.021) were independently related to LV remodeling. Peak LV torsion provided modest but significant incremental value over clinical, echocardiographic, and myocardial contrast echocardiography variables in predicting LV remodeling. By receiver-operating characteristics curve analysis, peak LV torsion ≤1.44°/cm provided the highest sensitivity (95%) and specificity (77%) to predict LV remodeling. Conclusions— LV torsion is significantly impaired early after AMI. The amount of impairment of LV torsion predicts LV remodeling at 6-month follow-up

First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers

A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists of replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 and E7. Twelve participants with a history of cervical intraepithelial neoplasia were included. Four cohorts of three participants were treated per dose level, ranging from 5 × 105 to 2.5 × 108 infectious particles per immunization. The participants received three immunizations with a 3-week interval. For immune monitoring, blood was drawn before immunization and 1 week after the second and third immunization. Immunization with Vvax001 was safe and well tolerated, with only mild injection site reactions, and resulted in both CD4+ and CD8+ T cell responses against E6 and E7 antigens. Even the lowest dose of 5 × 105 infectious particles elicited E6/E7-specific interferon (IFN)-γ responses in all three participants in this cohort. Overall, immunization resulted in positive vaccine-induced immune responses in 12 of 12 participants in one or more assays performed. In conclusion, Vvax001 was safe and induced immune responses in all participants. These data strongly support further clinical evaluation of Vvax001 as a therapeutic vaccine in patients with HPV-related malignancies

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Genetic association study of childhood aggression across raters, instruments, and age

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis AGGoverall was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations rg among rater-specific assessment of AGG ranged from rg= 0.46 between self- and teacher-assessment to rg= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range |rg|: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg=∼-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |rg| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.</p

What\u27s Old Is New Again: The Sacroiliac Joint as a Cause of Lateralizing Low Back Pain

It has not been easy to identify mechanical failure of the sacroiliac joint (SIJ) with traditional imaging. The integrated model of function (Lee and Vleeming, 1998) suggests that under normal circumstances, form and force closure combined contribute to sacral nutation and “locking” the SIJ for optimal load transfer. This model is supported by clinical evidence and scintigraphic findings that contribute to successful therapy in 80% of cases. Single-photon emission computed tomography and x-ray computed tomography (SPECT-CT), a hybrid device, was used in a study of 1200 patients (64% female and 36% male patients with an average age of 42 years; range, 15–78 years) with a clinical diagnosis of SIJ incompetence (pelvic girdle pain syndrome). Standard clinical testing and an alternate series of tests were used as a reference standard for imaging. Symptoms were present for a mean of 43 months. Imaging finding were of increased uptake in the upper SIJ (S1–S2), with extension into the dorsal interosseous ligament and measurable by count profile. Associated findings of tendon enthesopathy reflected altered biomechanics around the pelvis. Ipsilateral adductor enthesopathy was found in 70% and contralateral hamstring enthesopathy in 60% of patients. SPECT-CT criteria for the diagnosis of SIJ incompetence were developed and validated. SPECT-CT is a valid and reproducible technique for the diagnosis of SIJ incompetence with high concordance and specificity compared to the reference standards. Findings are supportive of the integrated model of SIJ function proposed by Lee and Vleeming