Intraoperative neurophysiological monitoring team's communiqué with anesthesia professionals.

BACKGROUND AND AIMS: Intraoperative neurophysiological monitoring (IONM) is the standard of care during many spinal, vascular, and intracranial surgeries. High-quality perioperative care requires the communication and cooperation of several multidisciplinary teams. One of these multidisciplinary services is intraoperative neuromonitoring (IONM), while other teams represent anesthesia and surgery. Few studies have investigated the IONM team's objective communication with anesthesia providers. We conducted a retrospective review of IONM-related quality assurance data to identify how changes in the evoked potentials observed during the surgery were communicated within our IONM-anesthesia team and determined the resulting qualitative outcomes. MATERIAL AND METHODS: Quality assurance records of 3,112 patients who underwent surgical procedures with IONM (from 2010 to 2015) were reviewed. We examined communications regarding perioperative evoked potential or electroencephalography (EEG) fluctuations that prompted neurophysiologists to alert/notify the anesthesia team to consider alteration of anesthetic depth/drug regimen or patient positioning and analyzed the outcomes of these interventions. RESULTS: Of the total of 1280 (41.13%) communications issued, there were 347 notifications and 11 alerts made by the neurophysiologist to the anesthesia team for various types of neuro/orthopedic surgeries. Prompt communication led to resolution of 90% of alerts and 80% of notifications after corrective measures were executed by the anesthesiologists. Notifications mainly related to limb malpositioning and extravasation of intravenous fluid. CONCLUSION: Based on our institutions' protocol and algorithm for intervention during IONM-supported surgeries, our findings of resolution in alerts and notifications indicate that successful communications between the two teams could potentially lead to improved anesthetic care and patient safety.

Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial.

BACKGROUND: Patients with systemic lupus erythematosus have T-cell dysfunction that has been attributed to the activation of the mammalian target of rapamycin (mTOR). Rapamycin inhibits antigen-induced T-cell proliferation and has been developed as a medication under the generic designation of sirolimus. We assessed safety, tolerance, and efficacy of sirolimus in a prospective, biomarker-driven, open-label clinical trial. METHODS: We did a single-arm, open-label, phase 1/2 trial of sirolimus in patients with active systemic lupus erythematosus disease unresponsive to, or intolerant of, conventional medications at the State University of New York Upstate Medical University (Syracuse, NY, USA). Eligible participants (aged ≥18 years) had active systemic lupus erythematosus fulfilling four or more of 11 diagnostic criteria defined by the American College of Rheumatology. We excluded patients with allergy or intolerance to sirolimus, patients with life-threatening manifestations of systemic lupus erythematosus, proteinuria, a urine protein to creatinine ratio higher than 0·5, anaemia, leucopenia, or thrombocytopenia. Patients received oral sirolimus at a starting dose of 2 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/mL. Patients were treated with sirolimus for 12 months. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. The primary efficacy endpoint was decrease in disease activity, assessed using the British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Blood samples of 56 matched healthy individuals were obtained as controls for immunobiological outcomes monitored at each visit. The primary efficacy endpoint was assessed in all patients who completed 12 months of treatment, and all patients who received at least one dose of treatment were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT00779194. FINDINGS: Between March 9, 2009, and Dec 8, 2014, 43 patients were enrolled, three of whom did not meet eligibility criteria. 11 of the 40 eligible patients discontinued study treatment because of intolerance (n=2) or non-compliance (n=9). SLEDAI and BILAG disease activity scores were reduced during 12 months of treatment in 16 (55%) of 29 patients who completed treatment. Mean SLEDAI score decreased from 10·2 (SD 5·6) at enrolment to 4·8 (4·5) after 12 months of treatment (p<0·001) and the mean total BILAG index score decreased from 28·4 (12·4) at enrolment to 17·4 (10·7) after 12 months of treatment (p<0·001). The mean daily dose of prednisone required to control disease activity decreased from 23·7 mg (SD 9·6) to 7·2 mg (2·3; p<0·001) after 12 months of treatment. Sirolimus expanded CD4+CD25+FoxP3+ regulatory T cells and CD8+ memory T-cell populations and inhibited interleukin-4 and interleukin-17 production by CD4+ and CD4-CD8- double-negative T cells after 12 months. CD8+ memory T cells were selectively expanded in SRI-responders. Patient liver function and lymphocyte counts were unchanged. Although HDL-cholesterol (Z=-2·50, p=0·012), neutrophil counts (Z=-1·92, p=0·054), and haemoglobin (Z=-2·83, p=0·005) were moderately reduced during treatment, all changes occurred within a range that was considered safe. Platelet counts were slightly elevated during treatment (Z=2·06, p=0·0400). INTERPRETATION: These data show that a progressive improvement in disease activity is associated with correction of pro-inflammatory T-cell lineage specification in patients with active systemic lupus erythematosus during 12 months of sirolimus treatment. Follow-up placebo-controlled clinical trials in diverse patient populations are warranted to further define the role of mTOR blockade in treatment of systemic lupus erythematosus. FUNDING: Pfizer, the National Institutes of Health, and the Central New York Community Foundation.

Transcranial Motor-Evoked Potentials Are More Readily Acquired Than Somatosensory-Evoked Potentials in Children Younger Than 6 Years.

BACKGROUND: There is a general belief that somatosensory-evoked potentials (SSEPs) are more easily obtained than transcranial motor-evoked potentials (TcMEPs) in children younger than 6 years. We tested this assumption and the assumption that motor-evoked potentials are rarely obtained in children younger than 2 years. METHODS: The records of all patients who were monitored during surgical procedures between April 1, 2010, and June 30, 2013, were reviewed and those who were younger than 72 months at the time of surgery were identified and analyzed for the rate of obtaining clinically useful SSEPs and motor-evoked potentials. Subgroup analysis was performed by age. RESULTS: A total of 146 patients were identified, 9 had SSEPs without TcMEPs monitored, 117 had both TcMEPs and SSEPs monitored, and the remainder had only electromyographic monitoring. All patients who were to have TcMEPs recorded received a total IV anesthetic. Among the 117 patients who had both SSEPs and TcMEPs monitored, clinically relevant TcMEPs were obtained more frequently than SSEPs (110/117 vs 89/117; χ = 14.82; P = 0.00012). There were significant differences between the rates of obtaining SSEPs and TcMEPs in the 0- to 23-month (P = 0.0038) and 24- to 47-month (P = 0.0056) age groups. Utilization of a double-train stimulation technique facilitated obtaining TcMEPs in the youngest patients. CONCLUSIONS: TcMEPs can be obtained more easily than SSEPs in patients younger than 72 months if a permissive anesthetic technique is used. The success rate for obtaining TcMEPs can be further enhanced by the use of a temporal facilitation (double-train) stimulation technique.

Liver injury correlates with biomarkers of autoimmunity and disease activity and represents an organ system involvement in patients with systemic lupus erythematosus.

Liver disease (LD), defined as ≥ 2-fold elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT), was examined in a longitudinal study of systemic lupus erythematosus (SLE) patients. Among 435 patients, 90 (20.7%) had LD with a greater prevalence in males (15/39; 38.5%) than females (75/396; 18.9%; p = 0.01). SLE disease activity index (SLEDAI) was greater in LD patients (7.8 ± 0.7) relative to those without (5.8 ± 0.3; p = 0.0025). Anti-smooth muscle antibodies, anti-DNA antibodies, hypocomplementemia, proteinuria, leucopenia, thrombocytopenia, and anti-phospholipid syndrome were increased in LD. An absence of LD was noted in patients receiving rapamycin relative to azathioprine, cyclosporine A, or cyclophosphamide. An absence of LD was also noted in patients treated with N-acetylcysteine. LFTs were normalized and SLEDAI was diminished with increased prednisone use in 76/90 LD patients over 12.1 ± 2.6 months. Thus, LD is attributed to autoimmunity and disease activity, it responds to prednisone, and it is potentially preventable by rapamycin or N-acetylcysteine treatment.

Cognitive Behavioural Therapy for anorexia nervosa: a systematic review.

Evidence for the effectiveness of psychological therapies for anorexia nervosa (AN) is inconsistent. There have been no systematic reviews solely on the effectiveness for Cognitive Behavioural Therapy (CBT) for AN. This review aimed to synthesise and appraise the recent evidence for CBT as a treatment for AN. Using specific search criteria, 16 relevant articles were identified which evaluated CBT alone or as part of a broader randomised/non-randomised trial. Various formats of CBT were utilised in the reviewed papers. Studies were evaluated using established quality criteria. The evidence reviewed suggested that CBT demonstrated effectiveness as a means of improving treatment adherence and minimising dropout amongst patients with AN. While CBT appeared to demonstrate some improvements in key outcomes (body mass index, eating-disorder symptoms, broader psychopathology), it was not consistently superior to other treatments (including dietary counselling, non-specific supportive management, interpersonal therapy, behavioural family therapy). Numerous methodological limitations apply to the available evidence. Further research and ongoing review is needed to evaluate the settings, patient groups and formats in which CBT may be effective as a treatment for AN.

Mechanistic target of rapamycin activation triggers IL-4 production and necrotic death of double-negative T cells in patients with systemic lupus erythematosus.

The mechanistic target of rapamycin (mTOR) is recognized as a sensor of mitochondrial dysfunction and effector of T cell lineage development; however, its role in autoimmunity, including systemic lupus erythematosus, remains unclear. In this study, we prospectively evaluated mitochondrial dysfunction and mTOR activation in PBLs relative to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) during 274 visits of 59 patients and 54 matched healthy subjects. Partial least square-discriminant analysis identified 15 of 212 parameters that accounted for 70.2% of the total variance and discriminated lupus and control samples (p < 0.0005); increased mitochondrial mass of CD3(+)/CD4(-)/CD8(-) double-negative (DN) T cells (p = 1.1 × 10(-22)) and FOXP3 depletion in CD4(+)/CD25(+) T cells were top contributors (p = 6.7 × 10(-7)). Prominent necrosis and mTOR activation were noted in DN T cells during 15 visits characterized by flares (SLEDAI increase ≥ 4) relative to 61 visits of remission (SLEDAI decrease ≥ 4). mTOR activation in DN T cells was also noted at preflare visits of SLE patients relative to those with stable disease or healthy controls. DN lupus T cells showed increased production of IL-4, which correlated with depletion of CD25(+)/CD19(+) B cells. Rapamycin treatment in vivo blocked the IL-4 production and necrosis of DN T cells, increased the expression of FOXP3 in CD25(+)/CD4(+) T cells, and expanded CD25(+)/CD19(+) B cells. These results identify mTOR activation to be a trigger of IL-4 production and necrotic death of DN T cells in patients with SLE.

Attention deficit and hyperactivity disorder scores are elevated and respond to N-acetylcysteine treatment in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate whether attention deficit hyperactivity disorder (ADHD) may serve as a marker of neuropsychiatric disease and as a target for N-acetylcysteine (NAC) treatment in patients with systemic lupus erythematosus (SLE). METHODS: The ADHD Self-Report Scale (ASRS) was used to assess 49 patients with SLE and 46 matched healthy control subjects. Twenty-four of the patients with SLE were randomized to receive either placebo, NAC at a dosage of 2.4 gm/day, or NAC at a dosage of 4.8 gm/day. Disease activity was evaluated monthly using the British Isles Lupus Assessment Group (BILAG) index, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the Fatigue Assessment Scale (FAS), and the ASRS, before and during the 3-month treatment period and after a 1-month washout period. RESULTS: The cognitive/inattentive (ASRS part A), hyperactivity/impulsive (ASRS part B), and combined (total) ASRS scores were increased in patients with SLE compared with control subjects (mean ± SEM 17.37 ± 1.03 [P = 3 × 10(-7) ], 14.51 ± 0.89 [P = 2 × 10(-4) ], and 31.92 ± 1.74 [P = 8 × 10(-7) ], respectively, versus 10.41 ± 1.02, 9.61 ± 1.21, and 20.02 ± 1.98, respectively. ASRS part A scores correlated with SLEDAI (r = 0.53, P < 0.0001) and BILAG scores (r = 0.36, P = 0.011). ASRS total scores also correlated with SLEDAI (r = 0.45, P = 0.0009) and BILAG scores (r = 0.31, P = 0.025). ASRS part A (r = 0.73, P < 0.0001), ASRS part B (r = 0.47, P = 0.0006), and ASRS total scores (r = 0.67, P < 0.0001) correlated with the FAS score. Relative to the scores in placebo-treated patients, ASRS total scores were reduced in SLE patients treated with NAC dosages of 2.4 gm/day and 4.8 gm/day combined (P = 0.037). ASRS part A scores were reduced by NAC dosages of 2.4 gm/day (P = 0.001) and 4.8 gm/day (P < 0.0001) as well as by NAC at dosages of 2.4 gm/day and 4.8 gm/day combined (P = 0.001). CONCLUSION: In patients with SLE, elevated ASRS scores reveal previously unrecognized and clinically significant symptoms of ADHD that respond to NAC treatment.

N-acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Systemic lupus erythematosus (SLE) patients exhibit T cell dysfunction, which can be regulated through mitochondrial transmembrane potential (Δψm) and mammalian target of rapamycin (mTOR) by glutathione (GSH). This randomized, double-blind, placebo-controlled study was undertaken to examine the safety, tolerance, and efficacy of the GSH precursor N-acetylcysteine (NAC). METHODS: A total of 36 SLE patients received either daily placebo or 1.2 gm, 2.4 gm, or 4.8 gm of NAC. Disease activity was evaluated monthly by the British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index (SLEDAI), and the Fatigue Assessment Scale (FAS) before, during, and after a 3-month treatment period. Mitochondrial transmembrane potential and mTOR were assessed by flow cytometry. Forty-two healthy subjects matched to patients for age, sex, and ethnicity were studied as controls. RESULTS: NAC up to 2.4 gm/day was tolerated by all patients, while 33% of those receiving 4.8 gm/day had reversible nausea. Placebo or NAC 1.2 gm/day did not influence disease activity. Considered together, 2.4 gm and 4.8 gm NAC reduced the SLEDAI score after 1 month (P = 0.0007), 2 months (P = 0.0009), 3 months (P = 0.0030), and 4 months (P = 0.0046); the BILAG score after 1 month (P = 0.029) and 3 months (P = 0.009); and the FAS score after 2 months (P = 0.0006) and 3 months (P = 0.005). NAC increased Δψm (P = 0.0001) in all T cells, profoundly reduced mTOR activity (P = 0.0009), enhanced apoptosis (P = 0.0004), reversed expansion of CD4-CD8- T cells (mean ± SEM 1.35 ± 0.12-fold change; P = 0.008), stimulated FoxP3 expression in CD4+CD25+ T cells (P = 0.045), and reduced anti-DNA production (P = 0.049). CONCLUSION: This pilot study suggests that NAC safely improves lupus disease activity by blocking mTOR in T lymphocytes.

Infection in systemic lupus erythematosus: friend or foe?

Infectious agents have long been implicated in the pathogenesis of systemic lupus erythematosus. Common viruses, such as the Epstein-Barr virus, transfusion transmitted virus, parvovirus and cytomegalovirus, have an increased prevalence in patients with systemic lupus erythematosus. They may contribute to disease pathogenesis through triggering autoimmunity via structural or functional molecular mimicry, encoding proteins that induce cross-reactive immune responses to self antigens or modulate antigen processing, activation, or apoptosis of B and T cells, macrophages or dendritic cells. Alternatively, some infectious agents, such as malaria, Toxoplasma gondii and Helicobacter pylori, may have a protective effect. Vaccinations may play dual roles by protecting against friend and foe alike.

Pharmacotherapy of systemic lupus erythematosus.

The pharmacological management of systemic lupus erythematosus (SLE) is challenging owing to its unpredictable clinical course, the variable organ system involvement and the lack of clear understanding of disease pathogenesis. The widely used corticosteroids and immunosuppressive drugs, which can control disease activity, have serious, potentially fatal, side effects. In the last decade, a better understanding of lupus pathogenesis has led to the development of biological agents that are directed at biomarkers. However, these biologicals also exert side effects due to infections resulting from completely eliminating immune cells (e.g., B cells) or cytokine signals (e.g., interferon-alpha) or affecting molecular targets outside the immune system (CD40L on platelets). New biomarker-driven clinical trials are ongoing to evaluate the safety and efficacy of B-cell depletion, blocking of interferon signaling, inhibition of the mTOR pathway, and restoration of glutathione deficiency in lupus T cells.

T-cell and B-cell signaling biomarkers and treatment targets in lupus.

PURPOSE OF REVIEW: Systemic lupus erythematosus is characterized by the production of antinuclear autoantibodies and dysfunction of T-cells, B-cells, and dendritic cells. Here, we review newly recognized genetic factors and mechanisms that underlie abnormal intracellular signal processing and intercellular communication within the immune system in systemic lupus erythematosus. RECENT FINDINGS: Activation of the mammalian target of rapamycin plays a pivotal role in abnormal activation of T and B-cells in systemic lupus erythematosus. In T-cells, increased production of nitric oxide and mitochondrial hyperpolarization were identified as metabolic checkpoints upstream of mammalian target of rapamycin activation. Mammalian target of rapamycin controls the expression T-cell receptor-associated signaling proteins CD4 and CD3zeta through increased expression of the endosome recycling regulator HRES-1/Rab4 gene, mediates enhanced Ca2+ fluxing and skews the expression of tyrosine kinases both in T and B-cells, and blocks the expression of Foxp3 and the expansion of regulatory T-cells. Mitochondrial hyperpolarization and the resultant ATP depletion predispose T-cells to necrosis, thus promoting the dendritic cell activation, antinuclear autoantibody production, and inflammation. SUMMARY: Mitochondrial hyperpolarization, increased activity of mammalian target of rapamycin and Syk kinases, enhanced receptor recycling and Ca2+ flux have emerged as common T and B-cell biomarkers and targets for treatment in systemic lupus erythematosus.

Hypertrophic osteoarthropathy masquerading as lower extremity cellulitis and response to bisphosphonates.

Hypertrophic osteoarthropathy (HOA) is characterized by clubbing of digits and, in more advanced stages, by periosteal new bone formation and synovial effusions. Secondary HOA typically occurs in the setting of intrathoracic malignancy, infections or lung metastases. We report a case with an atypical presentation of HOA. The prominent systemic signs, presentation limited to lower extremities only and an excellent response to bisphosphonates make this case unusual.

Coronary artery aneurysm related to percutaneous coronary intervention.

We report a case of coronary artery aneurysm possibly related to percutaneous coronary intervention. The various clinical features, epidemiology and management of the condition are also discussed in detail.

Obesity: effects on cardiovascular disease and its diagnosis.

The higher prevalence of cardiovascular disease in obese individuals is indirectly mediated, to a large extent, by the increased frequency of various well known risk factors like hypertension, diabetes, and dyslipidemia, either individually or as part of the metabolic syndrome. However, there are several ways in which obesity directly affects the cardiovascular system; these will be discussed in detail. We also focus on various challenges posed by obesity in the performance and interpretation of cardiac investigations and how they can be addressed.