Emotion Regulation and Psychological Dependence on Pain Medication among Hospital Outpatients with Chronic Spinal Pain: The Influence of Rumination about Pain and Alexithymia.

Objective: To examine the extent to which pain acceptance, pain catastrophising and alexithymia moderate associations between pain intensity and psychological pain medication dependence. Methods: Participants (106 hospital outpatients with chronic spinal pain) completed the Leeds Dependence Questionnaire (LDQ) to measure psychological dependence on pain medication, and the Chronic Pain Acceptance Questionnaire-8 (CPAQ-8), the Pain Catastrophising Scale (PCS) and the Toronto Alexithymia Scale-20 (TAS-20), plus the Depression, Anxiety and Stress Scale-21 (DASS-21). Results: Multiple linear regression showed that degree of psychological dependence (measured dimensionally across the range of LDQ scores) was associated with TAS subscale difficulty identifying feelings (DIF) (ß = 0.249, p = <0.002) and PCS subscale rumination (ß = 0.193, p = 0.030), independently of pain intensity and risk behaviors for medication misuse. The effect of pain intensity was moderated by rumination, with pain intensity more strongly associated with dependence when rumination was high (interaction ß = 0.192, p = 0.004). Logistic regression showed that the effect of pain intensity on severe dependence (measured categorically as LDQ score ≥ 20) was moderated by alexithymia, so that severe dependence was independently associated with the combination of intense pain and high alexithymia (interaction odds ratio = 7.26, 95% CIs = 1.63-32.42, p = 0.009). Conclusions: Rumination and alexithymia moderated the associations between pain intensity and psychological pain medication dependence, consistent with emotion regulation theory. This raises the possibility that specifically targeting rumination about pain and symptoms of alexithymia could potentially improve the effectiveness of psychological interventions for chronic pain and help people to avoid or reduce their psychological dependence on pain medication.

Protracted fibrinolysis resistance following cardiac surgery with cardiopulmonary bypass: A prospective observational study of clinical associations and patient outcomes.

BACKGROUND: Surgery on cardiopulmonary bypass (CPB) elicits a pleiomorphic systemic host response which, when severe, requires prolonged intensive care support. Given the substantial cross-talk between inflammation, coagulation, and fibrinolysis, the aim of this hypothesis-generating observational study was to document the kinetics of fibrinolysis recovery post-CPB using ClotPro® point-of-care viscoelastometry. Tissue plasminogen activator-induced clot lysis time (TPA LT, s) was correlated with surgical risk, disease severity, organ dysfunction and intensive care length of stay (ICU LOS). RESULTS: In 52 patients following CPB, TPA LT measured on the first post-operative day (D1) correlated with surgical risk (EuroScore II, Spearman's rho .39, p < .01), time on CPB (rho = .35, p = .04), disease severity (APACHE II, rho = .52, p < .001) and organ dysfunction (SOFA, rho = .51, p < .001) scores, duration of invasive ventilation (rho = .46, p < .01), and renal function (eGFR, rho = -.65, p < .001). In a generalized linear regression model containing TPA LT, CPB run time and markers of organ function, only TPA LT was independently associated with the ICU LOS (odds ratio 1.03 [95% CI 1.01-1.05], p = .01). In a latent variables analysis, the association between TPA LT and the ICU LOS was not mediated by renal function and thus, by inference, variation in the clearance of intraoperative tranexamic acid. CONCLUSIONS: This observational hypothesis-generating study in patients undergoing cardiac surgery with cardiopulmonary bypass demonstrated an association between the severity of fibrinolysis resistance, measured on the first post-operative day, and the need for extended postoperative ICU level support. Further examination of the role of persistent fibrinolysis resistance on the clinical outcomes in this patient cohort is warranted through large-scale, well-designed clinical studies.

Facet joint cyst haematoma: a rare cause of cauda equina syndrome.

Facet joint cysts are a feature of lumbar spondylosis and are an uncommon cause of radiculopathy. Facet joint cyst haematoma is a very rare entity and has previously been reported as a subacute cause of leg pain, back pain, sensory deficit and lower limb weakness. We present the unique case of facet joint cyst haematoma presenting as cauda equina syndrome. An 81 year old lady presented with a 7 day history of back pain and left foot drop, a 1 day history of perineal numbness and urinary retention with absent rectal tone, perianal anaesthesia and left leg hypoaesthesia. Emergency MRI scan demonstrated spinal canal stenosis as the aetiology of her cauda equina syndrome. She was taken to theatre for emergency lumbar decompression. At operation a facet joint haematoma compressing the cauda equina was found and extirpated with complete resolution of symptoms. In this case, the aetiology of cauda equina compression was not demonstrated effectively on pre-operative MRI scanning.

The ability of the logistic EuroSCORE to predict long-term outcomes after coronary artery bypass graft surgery.

OBJECTIVES: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) predicts in-hospital mortality for patients undergoing cardiac surgery. Many variables associated with increased surgical mortality persist postoperatively. The aim of this study was to investigate the predictive value of the logistic EuroSCORE to long-term survival after coronary artery bypass surgery. METHODS: Data were collected retrospectively for all patients undergoing coronary artery bypass graft (CABG) at a single center between January 1, 2009 and December 31, 2009. Data submitted to NICOR were used for EuroSCORE and in-hospital outcomes; longer-term, all-cause mortality from NHS digital Personal Demographic Service. Low (<3), intermediate (3-6), and high-risk (>6) logistic EuroSCORE groups were identified and analyzed using the appropriate statistical methodology, with p values less than .05 being taken as significant. RESULTS: Six hundred and sixty-three patients underwent isolated CABG procedures during the study. The 1-, 3-, 5-, and 10-year survival rates were 97.6%, 94.3%, 89.3%, and 73.5%, respectively. Comparing survival outcomes between low-, intermediate-, and high-risk groups showed that the logistic EuroSCORE was able to predict long-term outcomes (p < .05). In addition, poor left ventricular ejection fraction, serum creatinine above 200 ml, chronic pulmonary disease, extracardiac arteriopathy, and pulmonary hypertension were identified as independent predictors of long-term mortality. CONCLUSIONS: Our study demonstrates the logistic EuroSCORE predicted long-term outcomes following CABG surgery. This finding can inform patients of the long-term risks of CABG surgery and guide MDT decision-making.

Hospitalisation for degenerative cervical myelopathy in England: insights from the National Health Service Hospital Episode Statistics 2012 to 2019.

PURPOSE: Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction worldwide. However, the current incidence of DCM is poorly understood. The Hospital Episode Statistics (HES) database contains details of all secondary care admissions across NHS hospitals in England. This study aimed to use HES data to characterise surgical activity for DCM in England. METHODS: The HES database was interrogated for all cases of DCM between 2012 and 2019. DCM cases were identified from 5 ICD-10 codes. Age-stratified values were collected for 'Finished Consultant Episodes' (FCEs), which correspond to a patient's hospital admission under a lead clinician. Data was analysed to explore current annual activity and longitudinal change. RESULTS: 34,903 FCEs with one or more of the five ICD-10 codes were identified, of which 18,733 (53.6%) were of working age (18-64 years). Mean incidence of DCM was 7.44 per 100,000 (SD ± 0.32). Overall incidence of DCM rose from 6.94 per 100,000 in 2012-2013 to 7.54 per 100,000 in 2018-2019. The highest incidence was seen in 2016-2017 (7.94 per 100,000). The median male number of FCEs per year (2919, IQR: 228) was consistently higher than the median female number of FCEs per year (2216, IQR: 326). The rates of both emergency admissions and planned admissions are rising. CONCLUSIONS: The incidence of hospitalisation for DCM in England is rising. Health care policymakers and providers must recognise the increasing burden of DCM and act to address both early diagnoses and access to treatment in future service provision plans.

Cervical transforaminal epidural steroid injections for radicular pain : a systematic review.

AIMS: Cervical radiculopathy is a significant cause of pain and morbidity. For patients with severe and poorly controlled symptoms who may not be candidates for surgical management, treatment with transforaminal epidural steroid injections (CTFESI) has gained widespread acceptance. However, a paucity of high-quality evidence supporting their use balanced against perceived high risks of the procedure potentially undermines the confidence of clinicians who use the technique. We undertook a systematic review of the available literature regarding CTFESI to assess the clinical efficacy and complication rates of the procedure. METHODS: OVID, MEDLINE, and Embase database searches were performed independently by two authors who subsequently completed title, abstract, and full-text screening for inclusion against set criteria. Clinical outcomes and complication data were extracted, and a narrative synthesis presented. RESULTS: Six studies (three randomized controlled trials and three non-randomized observational studies; 443 patients) were included in the final review. The aggregate data support the efficacy of CTFESI in excess of the likely minimal clinically important difference. No major complications were described. CONCLUSION: There is increasing evidence supporting the efficacy of CTFESI. Concerns regarding the occurrence of catastrophic complications, widely shared in the case report and anecdotal literature, were not found when reviewing the best available evidence. However, the strength of these findings remains limited by the lack of highly powered high-level studies and the heterogeneity of the studies available. Further high-quality studies are recommended to address the issues of efficacy and safety with CTFESI. Cite this article: Bone Joint J 2022;104-B(5):567-574.

Patient-reported factors associated with degree of pain medication dependence and presence of severe dependence among spinal outpatients.

Aim: To identify risk factors for pain medication dependence. Materials & methods: Chronic spinal pain outpatients (n = 106) completed the Leeds Dependence Questionnaire (LDQ) and measures of potential risk factors. Participants with high (n = 3) and low (n = 3) dependence were interviewed. Results: Mean LDQ score was 11.52 (standard deviation 7.35) and 15/106 participants (14.2%) were severely dependent (LDQ ≥20). In linear regression, pain intensity (ß = 0.313, p < 0.001), being disabled by pain (ß = 0.355, p < 0.001), borrowing pain medication (ß = 0.209, p = 0.006), and emergency phone calls or clinic visits (ß = 0.169, p = 0.029) were associated with degree of dependence across the range of LDQ scores. In logistic regression, pain intensity (p = 0.001) and borrowing pain medication (p = 0.004) increased the odds of severe dependence. Interviewees described how their pain influenced their pain medication use and one described pain medication addiction. Conclusion: Interventions to reduce pain intensity and pain-related disability may reduce pain medication dependence.

This study examined painkiller dependence among 106 people with chronic spinal pain. Participants had mild to moderate dependence on average, but 14% (15/106) had severe dependence. Statistical analysis showed that having more intense pain, being disabled by pain, needing to borrow painkillers, and needing to make emergency phone calls or clinic visits because of pain were all related to increased dependence, and more intense pain and borrowing painkillers made severe dependence more likely. Six participants who were interviewed described how their pain influenced their painkiller use and they also described their concerns about using painkillers, including becoming addicted to painkillers. These findings can guide ways to help people with chronic spinal pain to reduce or avoid painkiller dependence.

The Relative Merits of Posterior Surgical Treatments for Multi-Level Degenerative Cervical Myelopathy Remain Uncertain: Findings from a Systematic Review.

OBJECTIVES: To assess the reporting of study design and characteristics in multi-level degenerative cervical myelopathy (DCM) treated by posterior surgical approaches, and perform a comparison of clinical and radiographic outcomes between different approaches. METHODS: A literature search was performed in Embase and MEDLINE between 1995-2019 using a sensitive search string combination. Studies were selected by predefined selection criteria: Full text articles in English, with >10 patients (prospective) or >50 patients (retrospective), reporting outcomes of multi-level DCM treated by posterior surgical approach. RESULTS: A total of 75 studies involving 19,510 patients, conducted worldwide, were identified. Laminoplasty was described in 56 studies (75%), followed by laminectomy with (36%) and without fusion (16%). The majority of studies were conducted in Asia (84%), in the period of 2016-2019 (51%), of which laminoplasty was studied predominantly. Twelve (16%) prospective studies and 63 (84%) retrospective studies were identified. The vast majority of studies were conducted in a single centre (95%) with clear inclusion/exclusion criteria and explicit cause of DCM. Eleven studies (15%) included patients with ossification of the posterior longitudinal ligament exclusively with cohorts of 57 to 252. The clinical and radiographic outcomes were reported with heterogeneity when comparing laminoplasty, laminectomy with and without fusion. CONCLUSIONS: Heterogeneity in the reporting of study and sample characteristics exists, as well as in clinical and radiographic outcomes, with a paucity of studies with a higher level of evidence. Future studies are needed to elucidate the clinical effectiveness of posterior surgical treatments.

Clinical outcomes after implantation of a sutureless aortic bioprosthesis with concomitant mitral valve surgery: the SURE-AVR registry.

BACKGROUND: Early treatment of aortic valve stenosis is recommended in eligible symptomatic patients with severe aortic valve stenosis who would otherwise have a poor prognosis. The sutureless aortic valve bioprosthesis offers an alternative to standard aortic valve replacement with a sutured valve, but limited data are available in patients who have undergone multiple valve procedures involving the new, sutureless technology. We sought to investigate outcomes in high operative risk patients with previous or concomitant valve surgery who were implanted with a sutureless valve. METHODS: SURE-AVR is an ongoing, prospective, multinational registry of patients undergoing aortic valve replacement. In-hospital and post-discharge outcomes up to 5 years were collected. RESULTS: The study population comprised 78 patients (mean ± SD: age 73.6 ± 7.6 years, logistic EuroSCORE 18.0 ± 17.5) enrolled at 13 sites who presented for concomitant or previous mitral valve repair (n = 45) or replacement (n = 33), with or without additional concomitant procedures, and were implanted with a sutureless valve. Mean ± SD overall aortic cross-clamp time was 109 ± 41 min and cardiopulmonary bypass time was 152 ± 49 min. Mean ± SD aortic pressure gradients decreased from 37.6 ± 17.7 mmHg preoperatively to 13.0 ± 5.7 mmHg at hospital discharge, and peak aortic pressure gradient from 61.5 ± 28.7 to 23.4 ± 10.6 mmHg. Early events included 1 death, 1 transient ischaemic attack, and 1 bleed (all 1.3%); a permanent pacemaker implantation was required in 6 patients (7.7%), and 2 reoperations (not valve related) (2.6%) took place. Over a median follow-up of 55.5 months (Q1 13.4, Q3 68.6), 12 patients died (6 cardiovascular and 6 non-cardiovascular, both 2.1% per patient-year). Five-year survival was 81.3%. Late paravalvular leak occurred in 2 patients (0.7% per patient-year) and permanent pacemaker implantation was required in 3 patients (0.1% per patient-year). There was no apparent rise in mean or peak aortic pressure gradient over the study. CONCLUSIONS: These results suggest that the sutureless implant is a technically feasible procedure during mitral surgery and is associated with good clinical outcomes.

Key Strategies for Clinical Management and Improvement of Healthcare Services for Cardiovascular Disease and Diabetes Patients in the Coronavirus (COVID-19) Settings: Recommendations From the REPROGRAM Consortium.

Patients with cardiovascular disease and diabetes are at potentially higher risk of infection and fatality due to COVID-19. Given the social and economic costs associated with disability due to these conditions, it is imperative that specific considerations for clinical management of these patients be observed. Moreover, the reorganization of health services around the pandemic response further exacerbates the growing crisis around limited access, treatment compliance, acute medical needs, and mental health of patients in this specific subgroup. Existing recommendations and guidelines emanating from respective bodies have addressed some of the pressure points; however, there are variations and limitations vis a vis patient with multiple comorbidities such as obesity. This article will pull together a comprehensive assessment of the association of cardiovascular disease, diabetes, obesity and COVID-19, its impact on the health systems and how best health systems can respond to mitigate current challenges and future needs. We anticipate that in the context of this pandemic, the cardiovascular disease and diabetes patients need a targeted strategy to ensure the harm to this group does not translate to huge costs to society and to the economy. Finally, we propose a triage and management protocol for patients with cardiovascular disease and diabetes in the COVID-19 settings to minimize harm to patients, health systems and healthcare workers alike.

Acute Neurological Care in the COVID-19 Era: The Pandemic Health System REsilience PROGRAM (REPROGRAM) Consortium Pathway.

The management of acute neurological conditions, particularly acute ischemic stroke, in the context of Coronavirus disease 2019 (COVID-19), is of importance, considering the risk of infection to the healthcare workers and patients and emerging evidence of the neuroinvasive potential of the virus. There are variations in expert guidelines further complicating the picture for clinicians in acute settings. In this light, there is a compelling need for further formulation of recommendations that compile these variations seen in the numerous guidelines present. Health system protocols for managing ongoing acute neurological care and intervention need consideration of safety and well-being of the frontline healthcare workers and the patients. We examine existing pathways and their efficacy to mitigate viral exposure to the healthcare workers and patients and synthesize a systemic approach to manage patients with acute neurological conditions in the COVID-19 scenario. Early experiences with a COVID-19 positive stroke patient treated with endovascular thrombectomy is presented to highlight the urgent need for adequate personal protective equipment (PPE) during acute neuro-interventional procedures.

Advancing spinal fellowship training: an international multi-centre educational perspective.

PURPOSE: The purpose of this article is to review the importance of contemporary spine surgery fellowships and educational strategies to assist with fellowship design and delivery. METHODS: Spine surgery fellowship includes trainees from orthopaedic and neurosurgical backgrounds and is increasingly indicated for individuals wishing to pursue spine surgery as a career, recognizing how spinal surgery evolved significantly in scope and complexity. We combine expert opinion with a review of the literature and international experience to expound spine fellowship training. RESULTS: Contemporary learning techniques include boot camps at the start of fellowship which may reinforce previous clinical learning and help prepare fellows for their new clinical roles. There is good evidence that surgical specialty training boot camps improve clinical skills, knowledge and trainee confidence prior to embarking upon new clinical roles with increasing levels of responsibility. Furthermore, as simulation techniques and technologies take on an increasing role in medical and surgical training, we found evidence that trainees' operative skills and knowledge can improve with simulated operations, even if just carried out briefly. Finally, we found evidence to suggest a role for establishing competence-based objectives for training in specific operative and technical procedures. Competence-based objectives are helpful for trainees and trainers to highlight gaps in a trainee's skill set that may then be addressed during training. CONCLUSIONS: Spinal fellowships may benefit from certain contemporary strategies that assist design and delivery of training in a safe environment. Interpersonal factors that promote healthy teamwork may contribute to an environment conducive to learning. These slides can be retrieved under Electronic Supplementary Material.

The Importance of Determining Trainee Perspectives on Procedural Competencies During Spine Surgery Clinical Fellowship.

STUDY DESIGN: Longitudinal survey. OBJECTIVE: It remains important to align competence-based objectives for training as deemed important by clinical fellows to those of their fellowship supervisors and program educators. The primary aim of this study was to determine trainee views on the relative importance of specific procedural training competencies. Secondarily, we aimed to evaluate self-perceived confidence in procedural performance at the commencement and completion of fellowship. METHODS: Questionnaires were administered to 68 clinical fellows enrolled in the AOSNA fellowship program during the 2015-2016 academic year. A Likert-type scale was used to quantify trainee perspectives on the relative importance of specific procedural competencies to their training base on an established curriculum including 53 general and 22 focused/advanced procedural competencies. We measured trainee self-perceived confidence in performing procedures at the commencement and completion of their program. Statistical analysis was performed on fellow demographic data and procedural responses. RESULTS: Our initial survey response rate was 82% (56/68) and 69% (47/68) for the follow-up survey. Although most procedural competencies were regarded of high importance, we did identify several procedures of high importance yet low confidence among fellows (ie, upper cervical, thoracic discectomy surgery), which highlights an educational opportunity. Overall procedural confidence increased from an average Likert score of 4.2 (SD = 1.3) on the initial survey to 5.4 (SD = 0.8) by follow-up survey (P < .0001). CONCLUSIONS: Understanding trainee goals for clinical fellowship remains important. Identification of areas of low procedural confidence and high importance to training experience will better guide fellowship programs and supervisors in the strategic delivery of the educational experience.

Integrative cross-platform analyses identify enhanced heterotrophy as a metabolic hallmark in glioblastoma.

BACKGROUND: Although considerable progress has been made in understanding molecular alterations driving gliomagenesis, the diverse metabolic programs contributing to the aggressive phenotype of glioblastoma remain unclear. The aim of this study was to define and provide molecular context to metabolic reprogramming driving gliomagenesis. METHODS: Integrative cross-platform analyses coupling global metabolomic profiling with genomics in patient-derived glioma (low-grade astrocytoma [LGA; n = 28] and glioblastoma [n = 80]) were performed. Identified programs were then metabolomically, genomically, and functionally evaluated in preclinical models. RESULTS: Clear metabolic programs were identified differentiating LGA from glioblastoma, with aberrant lipid, peptide, and amino acid metabolism representing dominant metabolic nodes associated with malignant transformation. Although the metabolomic profiles of glioblastoma and LGA appeared mutually exclusive, considerable metabolic heterogeneity was observed in glioblastoma. Surprisingly, integrative analyses demonstrated that O6-methylguanine-DNA methyltransferase methylation and isocitrate dehydrogenase mutation status were equally distributed among glioblastoma metabolic profiles. Transcriptional subtypes, on the other hand, tightly clustered by their metabolomic signature, with proneural and mesenchymal tumor profiles being mutually exclusive. Integrating these metabolic phenotypes with gene expression analyses uncovered tightly orchestrated and highly redundant transcriptional programs designed to support the observed metabolic programs by actively importing these biochemical substrates from the microenvironment, contributing to a state of enhanced metabolic heterotrophy. These findings were metabolomically, genomically, and functionally recapitulated in preclinical models. CONCLUSION: Despite disparate molecular pathways driving the progression of glioblastoma, metabolic programs designed to maintain its aggressive phenotype remain conserved. This contributes to a state of enhanced metabolic heterotrophy supporting survival in diverse microenvironments implicit in this malignancy.

Closure of the annulus fibrosus of the intervertebral disc using a novel suture application device-in vivo porcine and ex vivo biomechanical evaluation.

BACKGROUND CONTEXT: Defects in the annulus fibrosus (AF) remain a challenge in the surgical treatment of lumbar disc herniations with persistent defects, allowing potential re herniation of nucleus pulposus (NP) tissue. A cervical porcine model was chosen to simulate human lumbar intervertebral disc (IVD). PURPOSE: The aim of this study was to determine the technical feasibility of closure of the AF of the IVD using a novel minimally invasive Kerrison-shaped suture application device. STUDY DESIGN: Ex vivo biomechanical and in vivo porcine device evaluations were performed. METHODS: Ex vivo biomechanical evaluation: 15 porcine spinal units were explanted and subjected to mock discectomy. The annular defect was closed using 2-0 non-absorbable (ultra-high molecular-weight polyethylene, UHMWPE) suture and Dines knot. The knot was backed up with two, three, or four throws. The spinal unit was subject to 4000 cycles of flexion/extension with 1500 N of axial load, and assessed for knot slippage. In vivo porcine device evaluation: three pigs (53-57 kg) were anesthetized and underwent a ventral surgical approach to the cervical spine. The AF of two discs was incised, and simulated partial NP discectomy was performed. The defect was closed at one level using the AnchorKnot device to apply the suture with a Dines knot and four throws. The pigs were observed for 4 weeks before euthanasia, allowing 7T magnetic resonance imaging (MRI) and histological evaluation. RESULTS: A Dines knot with four throws experienced no slippage after 4000 cycles. This configuration was tested in vivo. Clinically, the neurological examination in treated pigs was normal following surgery. Histological and MRI assessment confirmed sustained defect closure at 4 weeks. There was no reaction to the suture material and no NP extrusion at any of the sutured levels. CONCLUSIONS: This study demonstrates that it is technically feasible to perform AF defect closure in a porcine model. This novel device achieved AF defect closure that was maintained through 4 weeks in vivo.

Modern Orthopedic Inpatient Care of the Orthopedic Patient With Diabetic Foot Disease.

In this article, we describe emergency and elective pathways within our orthopedic multidisciplinary inpatient care of patients with diabetic foot problems. We performed a retrospective cohort review of 19 complex patients requiring orthopedic surgical treatment of infected ulceration or Charcot feet or deformity at our institution. A total of 30 admissions (19 emergency, 11 elective) were included. The pathways were coordinated by a multidisciplinary team and comprised initial assessment and investigation and a series of key events, which consisted of emergency and elective surgery together with the introduction, and change of intravenous antibiotics when indicated. Patients had rigorous microbiological assessment, in the form of deep ulcer swabs, operative tissue specimens, joint aspirates, and blood cultures according to their clinical presentation as well as close clinical and biochemical surveillance, which expedited the prompt institution of key events. Outcomes were assessed using amputation rates and patient satisfaction. In the emergency group, there were 5.6 ± 3.0 (mean ± SD) key events per admission, including 4.2 ± 2.1 antibiotic changes. In the elective group, there were 4.8 ± 1.4 key events per inpatient episode, with 3.7 ± 1.3 antibiotic changes. Overall, there were 3 minor amputations, and no major amputations. The podiatric and surgical tissue specimens showed a wide array of Gram-positive, Gram-negative, aerobic and anaerobic isolates and 15% of blood cultures showed bacteremia. When 9 podiatric specimens were compared with 9 contemporaneous surgical samples, there was concordance in 2 out of 9 pairs. We have described the successful modern care of the orthopedic diabetic foot patient, which involves close clinical, microbiological, and biochemical surveillance by the multidisciplinary team directing patients through emergency and elective pathways. This has enabled successful surgical intervention involving debridement, pressure relief, and stabilization, with low rates of amputation.

Corpectomy with adjacent-level kyphoplasty to treat metastatic lung cancer in three contiguous cervical vertebrae causing focal neurologic compromise.

Study Design Case report. Objectives Decompression of metastatic spinal cord compression has been shown to improve quality of life and prolong ambulation in patients undergoing palliative treatment. We report a case of metastatic cervical myelopathy treated with a combined approach using corpectomy and stabilization together with balloon kyphoplasty to allow adequate decompression and immediate stability in a patient with significant destruction of adjacent vertebral bodies. Methods The cervical spine was approached anteriorly and decompressed with a C7 corpectomy. Subsequent stability was achieved with insertion of a trabecular metal cage. Balloon kyphoplasty was used to treat lytic lesions within the posterior body of the adjacent vertebrae for pain relief and increased stability. Additional stability was achieved through the application of an anterior plate. Results Full limited decompression and stabilization were successfully achieved. The patient had no further neurologic deterioration and made modest improvements that allowed a return to independent ambulation. Conclusion This limited approach may be an option for patients with metastatic spinal cord compression, lytic destruction of adjacent vertebral bodies, and limited life expectancy.

Evidence of superspin-glass behavior in Zn0.5Ni0.5Fe2O4 nanoparticles.

We have used dc-magnetization and ac-susceptibility to investigate the superspin dynamics in 9 nm average size Zn(0.5)Ni(0.5)Fe(2)O(4) magnetic particles at temperatures (T) between 3 and 300 K. Dc-magnetization M versus T data collected in a H = 50 Oe magnetic field using a field-cooled-zero-field-cooled protocol indicate that the onset of irreversibility occurs in the vicinity of 190 K. This is confirmed by M versus H|(T) hysteresis loops, as well as by frequency- and temperature-resolved ac-susceptibility data. We demonstrate that this magnetic event is not due to the blocking of individual superspins, but can be unequivocally ascribed to their collective freezing in a spin-glass-like fashion. Indeed, the relative variation (per frequency decade) of the in-phase susceptibility peak temperature is ∼0.032, critical dynamics analysis of this peak shift yields an exponent zν = 10.0 and a zero-field freezing temperature T(g) = 190 K, and, in a magnetic field, Tg(H) is excellently described by the de Almeida-Thouless line δT(g) = 1 - T(g)(H)/T(g) ∝ H(2/3). In addition, out-of-phase susceptibility versus temperature datasets collected at different frequencies collapse on a universal dynamic scaling curve. Finally, memory imprinting during a stop-and-wait magnetization protocol confirms the collective freezing nature of the state below 190 K.

Potential roles for prions and protein-only inheritance in cancer.

Inherited mutations are known to cause familial cancers. However, the cause of sporadic cancers, which likely represent the majority of cancers, is yet to be elucidated. Sporadic cancers contain somatic mutations (including oncogenic mutations); however, the origin of these mutations is unclear. An intriguing possibility is that a stable alteration occurs in somatic cells prior to oncogenic mutations and promotes the subsequent accumulation of oncogenic mutations. This review explores the possible role of prions and protein-only inheritance in cancer. Genetic studies using lower eukaryotes, primarily yeast, have identified a large number of proteins as prions that confer dominant phenotypes with cytoplasmic (non-Mendelian) inheritance. Many of these have mammalian functional homologs. The human prion protein (PrP) is known to cause neurodegenerative diseases and has now been found to be upregulated in multiple cancers. PrP expression in cancer cells contributes to cancer progression and resistance to various cancer therapies. Epigenetic changes in the gene expression and hyperactivation of MAP kinase signaling, processes that in lower eukaryotes are affected by prions, play important roles in oncogenesis in humans. Prion phenomena in yeast appear to be influenced by stresses, and there is considerable evidence of the association of some amyloids with biologically positive functions. This suggests that if protein-only somatic inheritance exists in mammalian cells, it might contribute to cancer phenotypes. Here, we highlight evidence in the literature for an involvement of prion or prion-like mechanisms in cancer and how they may in the future be viewed as diagnostic markers and potential therapeutic targets.

Targeting radiation-induced G(2) checkpoint activation with the Wee-1 inhibitor MK-1775 in glioblastoma cell lines.

The purpose of this study was to determine the capacity of MK-1775, a potent Wee-1 inhibitor, to abrogate the radiation-induced G(2) checkpoint arrest and modulate radiosensitivity in glioblastoma cell models and normal human astrocytes. The radiation-induced checkpoint response of established glioblastoma cell lines, glioblastoma neural stem (GNS) cells, and astrocytes were determined in vitro by flow cytometry and in vivo by mitosis-specific staining using immunohistochemistry. Mechanisms underlying MK-1775 radiosensitization were determined by mitotic catastrophe and γH2AX expression. Radiosensitivity was determined in vitro by the clonogenic assay and in vivo by tumor growth delay. MK-1775 abrogated the radiation-induced G(2) checkpoint and enhanced radiosensitivity in established glioblastoma cell lines in vitro and in vivo, without modulating radiation response in normal human astrocytes. MK-1775 appeared to attenuate the early-phase of the G(2) checkpoint arrest in GNS cell lines, although the arrest was not sustained and did not lead to increased radiosensitivity. These results show that MK-1775 can selectively enhance radiosensitivity in established glioblastoma cell lines. Further work is required to determine the role Wee-1 plays in checkpoint activation of GNS cells.