Musculoskeletal Tuberculosis: New Insights on Diagnosis Strategy and Treatment.

BACKGROUND/ OBJECTIVE: Skeletal tuberculosis (TB) is rare. We aimed to report on diagnostic strategy and treatment of skeletal TB. METHODS: In this multidisciplinary single-center medical records review study, all adult patients admitted between January 2009 and December 2019 with microbiologically proven skeletal TB were included. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records. RESULTS: Among 184 patients identified with TB, 21 (16 women, 42 years [27, 48 years]) had skeletal involvement. Skeletal TB included spondylitis (n = 11), lytic bone lesions (n = 7), sacroiliitis (n = 5), arthritis (n = 3), osteitis (n = 2), and diffuse muscle abscesses without bone lesion (n = 1). Lytic lesions involved both axial and peripheral skeleton at multiple sites in most cases. 18F-fluorodeoxyglucose positron emission tomography was performed in 13 patients and helped to detect multifocal asymptomatic lesions and to target biopsy. All patients were treated with anti-TB therapy for 7 to 18 months. Fifteen patients (71.4%) received steroids as an adjunct therapy. Eleven patients needed an orthopedic immobilization corset, and 3 patients underwent surgery. All patients clinically improved under treatment, but 2 relapsed over a median follow-up of 24 months (12-30 months). No patient died or suffered long-term disabilities. CONCLUSION: Our study emphasizes the diversity of skeletal involvement in TB. 18F-fluorodeoxyglucose positron emission tomography scanner at diagnosis is key to assess the extension of skeletal involvement and guide extraskeletal biopsy. Neurological complications might be prevented by adding corticosteroids to anti-TB therapy.

Postoperative Delirium is Associated With Prolonged Head and Neck Resection and Reconstruction Surgery: An Institutional Study.

PURPOSE: Delirium is a recognized complication of surgery. It has a deleterious effect on a patient's postoperative recovery and well-being. The purpose of this study was to estimate the frequency and identify the risk factors for the development of postoperative delirium (POD) in a cohort of patients who underwent extensive head and neck surgery (HNS) of greater than five hours duration. MATERIALS AND METHODS: The authors undertook a retrospective cohort study of patients who underwent HNS of greater than five hours duration. The primary predictor variables comprised a set of risk factors (sociodemographic, disease-specific, duration of surgery, and duration of inpatient stay) that were thought to be associated with the development of POD. The primary outcome variable was the development of POD. Descriptive, bivariate, and multivariate statistical analysis was undertaken, and significance was set at P < .05. RESULTS: One hundred and seventy patients were included in the study. There were 124 males and 46 females. Forty patients (23.53%) developed POD: 30 documented and 10 inferred. The mean age of the POD cohort was 65 years (SD 13), with a median age of 69 years. The occurrence of POD was statistically related to increased age, mental health status, American Society of Anesthesiologists (ASA) score, and drug dependence (either illicit or prescription). POD and operative duration were statistically associated. POD and length of stay were not statistically associated. CONCLUSION: Delirium did occur postoperatively in 23.53% of our patients who underwent extensive and prolonged HNS. POD may go unrecognized by treating teams. As POD has a deleterious effect on the cognitive function, it is important to identify and aggressively treat episodes of POD that occur during a patient's postoperative recovery.

Lack of discreet colocalization of epithelial apoptosis to the atretic precursor in the colon of the Fibroblast growth factor receptor 2IIIb mouse and staining consistent with cellular movement suggest a revised model of atresia formation.

BACKGROUND: Colonic atresias in the Fibroblast growth factor receptor 2IIIb (Fgfr2IIIb) mouse model have been attributed to increased epithelial apoptosis and decreased epithelial proliferation at embryonic day (E) 10.5. We therefore hypothesized that these processes would colocalize to the distal colon where atresias occur (atretic precursor) and would be excluded or minimized from the proximal colon and small intestine. RESULTS: We observed a global increase in intestinal epithelial apoptosis in Fgfr2IIIb -/- intestines from E9.5 to E10.5 that did not colocalize to the atretic precursor. Additionally, epithelial proliferations rates in Fgfr2IIIb -/- intestines were statistically indistinguishable to that of controls at E10.5 and E11.5. At E11.5 distal colonic epithelial cells in mutants failed to assume the expected pseudostratified columnar architecture and the continuity of the adjacent basal lamina was disrupted. Individual E-cadherin-positive cells were observed in the colonic mesenchyme. CONCLUSIONS: Our observations suggest that alterations in proliferation and apoptosis alone are insufficient to account for intestinal atresias and that these defects may arise from both a failure of distal colonic epithelial cells to develop normally and local disruptions in basal lamina architecture.

Handoffs and the challenges to implementing teamwork training in the perioperative environment.

Perioperative handoffs are high-risk events for miscommunications and poor care coordination, which cause patient harm. Extensive research and several interventions have sought to overcome the challenges to perioperative handoff quality and safety, but few efforts have focused on teamwork training. Evidence shows that team training decreases surgical morbidity and mortality, and there remains a significant opportunity to implement teamwork training in the perioperative environment. Current perioperative handoff interventions face significant difficulty with adherence which raises concerns about the sustainability of their impact. In this perspective article, we explain why teamwork is critical to safe and reliable perioperative handoffs and discuss implementation challenges to the five core components of teamwork training programs in the perioperative environment. We outline evidence-based best practices imperative for training success and acknowledge the obstacles to implementing those best practices. Explicitly identifying and discussing these obstacles is critical to designing and implementing teamwork training programs fit for the perioperative environment. Teamwork training will equip providers with the foundational teamwork competencies needed to effectively participate in handoffs and utilize handoff interventions. This will improve team effectiveness, adherence to current perioperative handoff interventions, and ultimately, patient safety.

Long-term follow-up in patients with coeliac disease in the pandemic-era: a view from Sheffield the NHS England national centre for adult coeliac disease.

Aim: To explore patients' follow-up preferences. Background: Optimal follow-up strategies for patients with coeliac disease remain a subject of debate. Research suggests patients' prefer review by dietitians with a doctor available as required. Methods: Patients with coeliac disease under review at our centre, completed a questionnaire assessing their views on what makes follow-up useful based on specific criteria. Bloods tests, symptoms review, dietary assessment, opportunity to ask questions and reassurance. Patients' preferences between follow-up with a hospital doctor, a hospital dietitian, a hospital dietitian with a doctor available, a general practitioner, no follow-up or access when needed were also evaluated. Results: 138 adult patients completed the questionnaire, 80% of patients reported following a strict gluten free diet (mean diagnosis was 7.2 years). Overall, 60% found their follow-up to be 'very useful' valuing their review of blood tests and symptoms (71%) reassurance (60%) and opportunity to ask questions (58%). Follow-up by a dietitian with a doctor available was the most preferred option of review (p<0.001) except when compared to hospital doctor (p=0.75). Novel modalities of follow-up such as telephone and video reviews were regarded as of equal value to face-to-face appointments (65% and 62% respectively). Digital applications were significantly less preferable (38%, p<0.001). Conclusion: Follow-up by a dietitian with a doctor available as needed was the most preferred follow-up method. However, in this study follow-up by a dietitian with doctor available and hospital doctor alone was statistically equivalent. Many patients consider telephone and video follow-up of equal value to face-to-face reviews.

Profound seizure suppression and disease modification by targeting JAK1, a key driver of a pro-epileptogenic gene network.

Epilepsy is the 4th most prevalent neurological disorder with over 50 million cases worldwide. While a number of drugs exist to suppress seizures, approximately 1/3 of patients remain drug resistant, and no current treatments are disease modifying. Using network and systems-based approaches, we find that the histone methylase EZH2 suppresses epileptogenesis and slows disease progression, via repression of JAK1 and STAT3 signaling in hippocampal neurons. Pharmacological inhibition of JAK1 with the orally available, FDA-approved drug CP690550 (Tofacitinib) profoundly suppresses behavioral and electrographic seizures after the onset of epilepsy across preclinical rodent models of acquired epilepsy. This seizure suppression persists for weeks after drug withdrawal. Identification of an endogenous protective response to status epilepticus in the form of EZH2 induction has highlighted a critical role for the JAK1 kinase and STAT3 in both the initiation and propagation of epilepsy across preclinical rodent models and human disease. Overall, we find that STAT3 is transiently activated after insult, reactivates with spontaneous seizures, and remains targetable for disease modification in chronic epilepsy.

Emergency Medical Response for Non-Hospitalized Person Events in a Children's Hospital.

OBJECTIVES: Hospital-based code blue (CB) teams are designed for hospitalized patients (HP) with unanticipated medical emergencies outside of an ICU. At our freestanding pediatric institution, the same team responds to CB calls involving nonhospitalized persons (NHP) throughout the hospital campus. We hypothesized there are significant differences between the characteristics of NHP and HP requiring emergency medical response, and most responses for NHP do not require advanced critical care. METHODS: We analyzed a retrospective cohort of CB responses at our large, urban, academic children's medical center from January to December 2017. We evaluated the demographic and clinical characteristics of these HP compared with NHP events. RESULTS: There were 168 CB activations during the study, of which 135 (80.4%) were for NHP. Ninety-one (67.4%) of the NHP responses involved adults (age >18 years) compared with 6 (18.2%) of the HP. Triggers for CB team activation for NHP were most frequently syncope (42.2%), seizure (10.3%), or fall (9.6%) compared with seizure (30.3%), hypoxia (27.3%), or anaphylaxis (12.1%) for HP. Critical interventions such as bag-mask ventilation and cardiopulmonary resuscitation were infrequently performed for either cohort. CONCLUSIONS: CB activations in our pediatric institution more often involve NHP than HP. NHP responses are more likely to involve adults and infrequently require advanced interventions. Use of a pediatric CB team for NHP events may be an unnecessary use of pediatric critical care resources. Future studies are warranted to evaluate the most effective team composition, training, and response system for NHP in a freestanding children's hospital.

Emergency Medical Response for Non-Hospitalized Person Events in a Children's Hospital.

OBJECTIVES: Hospital-based code blue (CB) teams are designed for hospitalized patients (HP) with unanticipated medical emergencies outside of an ICU. At our freestanding pediatric institution, the same team responds to CB calls involving nonhospitalized persons (NHP) throughout the hospital campus. We hypothesized there are significant differences between the characteristics of NHP and HP requiring emergency medical response, and most responses for NHP do not require advanced critical care. METHODS: We analyzed a retrospective cohort of CB responses at our large, urban, academic children's medical center from January to December 2017. We evaluated the demographic and clinical characteristics of these HP compared with NHP events. RESULTS: There were 168 CB activations during the study, of which 135 (80.4%) were for NHP. Ninety-one (67.4%) of the NHP responses involved adults (age >18 years) compared with 6 (18.2%) of the HP. Triggers for CB team activation for NHP were most frequently syncope (42.2%), seizure (10.3%), or fall (9.6%) compared with seizure (30.3%), hypoxia (27.3%), or anaphylaxis (12.1%) for HP. Critical interventions such as bag-mask ventilation and cardiopulmonary resuscitation were infrequently performed for either cohort. CONCLUSIONS: CB activations in our pediatric institution more often involve NHP than HP. NHP responses are more likely to involve adults and infrequently require advanced interventions. Use of a pediatric CB team for NHP events may be an unnecessary use of pediatric critical care resources. Future studies are warranted to evaluate the most effective team composition, training, and response system for NHP in a freestanding children's hospital.

HeartWatch: Implementing a Pediatric Heart Center Program to Prevent Cardiac Arrests Outside the ICU.

Pediatric patients with cardiovascular disease are at increased risk of cardiopulmonary arrest. Despite utilization of Cardiac Pediatric Early Warning Scores to identify patients at risk of decompensation, our institution had a twofold increase in cardiac arrests (CAs) in the acute care cardiology unit (ACCU) over 2 years. Through a quality improvement initiative, we developed a watcher program, HeartWatch, to reduce the CA arrest rate in the ACCU by 50% over the first year of implementation. Methods: HeartWatch aims to identify patients not adequately captured by Cardiac Pediatric Early Warning Scores who are at high risk for sudden decompensation. Inclusion criteria were developed and evaluated during pilot and implemented phases (April 2020-April 2021) and then monitored in a sustained phase through June 2022. Our primary outcome was the reduction in the out-of-ICU CA rate. Results: During the 13 months, we enrolled 169 patients, and the CA rate decreased from 0.7 to 0.33 per 1,000 patient days, a 53% reduction. The CA rate further decreased to 0.28 events per 1,000 patient days, a 60% reduction, by June 2022. The most common indications for HeartWatch inclusion were high-risk single-ventricle patients (31%) and patients with diminished ventricular function (20%). Conclusions: Implementation of HeartWatch was associated with a meaningful reduction in CA in the ACCU. Creating shared mental models for high-risk patients is essential for patient safety. Future work will optimize local processes that focus on the sustainability of our gains. We will also evaluate opportunities to adapt and implement a similar framework in other institutions to assess reproducibility.

Detrimental ELAVL-1/HuR-dependent GSK3ß mRNA stabilization impairs resolution in acute respiratory distress syndrome.

A hallmark of acute respiratory distress syndrome (ARDS) is accumulation of protein-rich edema in the distal airspaces and its removal is critical for patient survival. Previous studies have shown a detrimental role of Glycogen Synthase Kinase (GSK) 3ß during ARDS via inhibition of alveolar epithelial protein transport. We hypothesized that post-transcriptional regulation of GSK3ß could play a functional role in ARDS resolution. To address this hypothesis, we performed an in silico analysis to identify regulatory genes whose expression correlation to GSK3ß messenger RNA utilizing two lung cancer cell line array datasets. Among potential regulatory partners of GSK3ß, these studies identified the RNA-binding protein ELAVL-1/HuR (Embryonic Lethal, Abnormal Vision, Drosophila-Like) as a central component in a likely GSK3ß signaling network. ELAVL-1/HuR is a RNA-binding protein that selectively binds to AU-rich elements of mRNA and enhances its stability thereby increasing target gene expression. Subsequent studies with siRNA suppression of ELAVL-1/HuR demonstrated deceased GSK3ß mRNA and protein expression and improved clearance of FITC-albumin in A549 cells. Conversely, stabilization of ELAVL-1/HuR with the proteasome inhibitor MG-132 resulted in induction of GSK3ß at mRNA and protein level and attenuated FITC-albumin clearance. Utilizing ventilator-induced lung injury or intra-tracheal installation of hydrochloric acid to induce ARDS in mice, we observed increased mRNA and protein expression of ELAVL-1/HuR and GSK3ß. Together, our findings indicate a previously unknown interaction between GSK3ß and ELAV-1 during ARDS, and suggest the inhibition of the ELAV-1- GSK3ß pathways as a novel ARDS treatment approach.

Correction: Detrimental ELAVL-1/HuR-dependent GSK3ß mRNA stabilization impairs resolution in acute respiratory distress syndrome.

[This corrects the article DOI: 10.1371/journal.pone.0172116.].

Publication outcomes of abstracts presented at an American College of Rheumatology/Association of Rheumatology Health Professionals annual scientific meeting.

OBJECTIVE: The American College of Rheumatology (ACR) and the Association of Rheumatology Health Professionals (ARHP) Annual Scientific Meeting is an important forum for early dissemination of novel ideas. However, unlike published studies in peer-reviewed journals, reviewers select abstracts based solely on a general summary of the research. Analyses of the scientific impact and the publication record of the ACR/ARHP Annual Meeting have not been previously described. This study characterizes publication trends and outcomes associated with abstracts presented at the ACR/ARHP Annual Scientific Meeting. METHODS: We identified all abstracts accepted for oral or poster presentation at the 2006 ACR/ARHP Annual Scientific Meeting. Using a defined search algorithm, we conducted a manual PubMed search for each accepted abstract, which was repeated by a custom computerized search, and analyzed the resulting journal title, impact factor, and time to publication. RESULTS: A total of 2,149 abstracts were analyzed. The overall publication ratio was 59.1%. The mean ± SD time from abstract presentation to publication was 18.2 ± 15.2 months with a mean ± SD impact factor of 5.61 ± 4.20. Overall, studies presented in oral format were significantly more likely to be published than poster presentations (P < 0.0001). The average time to publication was significantly shorter for basic science studies than clinical research studies (P < 0.0001). The average journal impact factor of published studies presented in oral format was significantly higher than those presented as posters (P < 0.0001). CONCLUSION: These results reflect high research productivity with a publication ratio of approximately 60% for abstracts presented at the 2006 Annual Scientific Meeting.

Diffuse spine involvement in sarcoidosis with sternal lytic lesions: two case reports.

STUDY DESIGN: Case report. OBJECTIVE: To report 2 cases of sarcoidosis with a diffuse vertebral involvement, associated with a rare location in the sternum. SUMMARY OF BACKGROUND DATA: Sarcoidosis is a systemic disease of unknown cause with various clinical and radiologic manifestations. Bone involvement is rare (1%-13% of cases). Vertebral involvement is very uncommon. Lytic lesions, sclerotic lesions, or both of these patterns may be observed. METHODS: One patient complained of diffuse bone pain; the second patient was asymptomatic. Each patient had radiograph, CT, and MRI of the spine. The second patient also underwent a PET/CT FDG-(18F). Sternal bone biopsy was performed in both patients. Pathologic findings indicated typical pattern of bone sarcoidosis. Clinical and biologic improvement was noticed after treatment with corticosteroids. RESULTS: In our 2 cases, radiograph, CT, MRI, and PET/CT findings were evocative of diffuse spine involvement in sarcoidosis associated with sternal lytic lesions. This suspicion was confirmed by histopathologic findings, which found a typical pattern of sarcoidosis. CONCLUSION: These 2 cases emphasize the value of CT, MRI, and FDG-(18F) PET/CT for the diagnosis of diffuse spinal involvement in sarcoidosis and describe an exceptional association with sternal lytic lesions.