A Comprehensive Review of the Celiac Plexus Block for the Management of Chronic Abdominal Pain.

PURPOSE OF REVIEW: Chronic abdominal pain (CAP) is a significant health problem that can dramatically affect quality of life and survival. Pancreatic cancer is recognized as one of the most painful malignancies with 70-80% suffering from substantial pain, often unresponsive to typical medical management. Celiac plexus neurolysis and celiac plexus block (CPB) can be performed to mitigate pain through direct destruction or blockade of visceral afferent nerves. The objective of this manuscript is to provide a comprehensive review of the CPB as it pertains to CAP with a focus on the associated anatomy, indications, techniques, neurolysis/blocking agents, and complications observed in patients who undergo CPB for the treatment of CAP. RECENT FINDINGS: The CAP is difficult to manage due to lack of precision in diagnosis and limited evidence from available treatments. CAP can arise from both benign and malignant causes. Treatment options include pharmacologic, interventional, and biopsychosocial treatments. Opioid therapy is typically utilized for the treatment of CAP; however, opioid therapy is associated with multiple complications. CPB has successfully been used to treat a variety of conditions resulting in CAP. The majority of the literature specifically related to CPB is surrounding chronic pain associated with pancreatic cancer. The literature shows emerging evidence in managing CAP with CPB, specifically in pancreatic cancer. This review provides multiple aspects of CAP and CPB, including anatomy, medical necessity, indications, technical considerations, available evidence, and finally complications related to the management.

Managing atopic dermatitis with systemic therapies in adults and adolescents: An Australian/New Zealand narrative.

With the rapid development of new, targeted therapies for the treatment of moderate/severe atopic dermatitis, it is opportune to review the available conventional systemic agents. We assess the published evidence for systemic therapies for atopic dermatitis and amalgamate this with real-world experience. Discussions are centred on when systemic therapy should be considered, which drug(s), what dose, how to sequence or combine these therapies, how long they should be continued for and what is considered success.

Psoriasis and cancer. An Australian/New Zealand narrative.

Patients with psoriasis have an increased risk of cancer, which may be due to impaired immune surveillance, immune modulatory treatments, chronic inflammation and/or co-risk factors such as obesity. The increase in treatment-independent solid cancers, including urinary/bladder cancers, oropharynx/larynx, liver/gallbladder and colon/rectal cancers, seem to be linked to alcohol and smoking. Lung cancer and nonmelanoma skin cancer are also increased in patients with psoriasis. The risk of nonmelanoma skin cancer increases with age and severity of psoriasis. It is also higher in men, particularly for squamous cell carcinoma, which may reflect previous exposure to PUVA and/or ciclosporin. The risk of cutaneous T-cell lymphoma is substantially higher in patients with moderate-to-severe psoriasis. Biologic therapies are independently associated with a slight increase risk of cancer, but this is less than ciclosporin, with the risk confounded by disease severity and other co-risk factors. The risk of cancer from low-dose methotrexate is likely minimal. In contrast, acitretin is likely protective against a variety of solid and haematological malignancies. The data on small molecule therapies such as apremilast are too immature for comment, although no signal has yet been identified. The decision whether to stop psoriasis immune modulatory treatments following a diagnosis of cancer, and when to resume, needs to be considered in the context of the patients' specific cancer. However, there is no absolute need to stop any treatment other than possibly ciclosporin, unless there is a concern over an increased risk of serious infection or drug-drug interaction with cancer-directed therapies, including radiotherapy.

Psoriasis and infection. A clinical practice narrative.

The Australasian Psoriasis Collaboration has developed a clinical practice narrative with respect to the relationship between psoriasis, its treatment and infection. The cutaneous microbiome of patients with psoriasis is different to those without psoriasis, although the significance of this is unclear. Whilst a wide range of microorganisms has been associated with psoriasis (including ß-haemolytic streptococci, Staphylococcus aureus, Porphyromonas gingivalis, Candida albicans, Chlamydia psittaci, human immunodeficiency virus and hepatitis C virus), there is limited evidence that antimicrobial therapy is of direct benefit in preventing flares of psoriasis. Psoriasis is independently associated with an increased risk of serious infection, but the absolute risk is low. The risk of serious infections is further increased with immune-modulatory treatments. The decision whether to, and when to, stop or resume immune-modulatory treatment after a serious infection has occurred depends on risk assessment for that patient, taking into account the infection being treated, the risk of recurrent infection, any interventions that can modify the risk and the need for psoriasis control. Live vaccines (e.g. MMR, varicella, zoster and yellow fever) are generally contraindicated in patients with psoriasis on immune-modulatory agents, but this depends on the degree of immune suppression and individual risk factors. Wound healing in psoriasis is normal. Treatment with infliximab, adalimumab, etanercept, methotrexate and ciclosporin can safely be continued through low-risk surgical procedures. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient's individual risk factors and comorbidities.

Psoriasis in those planning a family, pregnant or breast-feeding. The Australasian Psoriasis Collaboration.

The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast-feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti-psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro-developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast-feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super-potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus.

The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting.

The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low-dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti-inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non-fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at-risk groups include an HIV test, a QuantiFERON-TB Gold test and a chest X-ray. In patients without complications, repeat the FBC at 2-4 weeks, then every 3-6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low-dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment-emergent liver toxicity is related to underlying metabolic syndrome and non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: '20 mg/day' has been corrected to '20 gm/day'.] Although MTX is a potential teratogen post-conception, there is little evidence for this pre-conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri-surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti-tumour necrosis factor biologics.

A universal assay for the detection of siderophore activity in natural waters.

Siderophores, a family of biogenic metal chelating agents, play critical roles in the biogeochemical cycling of Fe and other metals by facilitating their solubilization and uptake in circumneutral to alkaline oxic environments. However, because of their small concentrations (ca. nM) and large number of molecular structures, siderophore detection and quantification in environmental samples requires specialized equipment and expertise, and often requires pre-concentration of samples, which may introduce significant bias. The "universal" CAS assay, which was originally designed for use in bacterial cultures, quantifies the iron chelating function of a pool of siderophores but only at concentrations (>2 µM) well above the concentrations estimated to be present in marine, freshwater, and soil samples. In this manuscript, we present a high sensitivity modification of this universal assay (HS-CAS) suitable for detecting and quantifying siderophore activity in the nM concentration range, allowing for direct quantitation of siderophore reactivity in transparent aqueous samples.

The moderating impact of temporal separation on the association between intention and physical activity: a meta-analysis.

Previous meta-analyses have estimated that the intention-behaviour association in physical activity (PA) is large in magnitude. However, these prior meta-analyses have also revealed a large degree of heterogeneity, suggesting the presence of moderating variables. This study examines the impact of one such moderator, testing the hypothesis that the magnitude of the association between intention and behaviour decreases as the temporal separation between the two increases. A systematic literature search was used to identify published and unpublished studies that met the inclusion criteria. A random-effects meta-regression was conducted to test the study hypothesis. A total of 78 journal articles and 11 unpublished dissertations were identified, yielding 109 effect sizes. The mean number of weeks between the measurement of intention and behaviour was 5.4 (SD = 6.6, range = .43, 26). The average correlation between intention and behaviour was r = 0.51. In line with theoretical predictions, temporal separation was a significant moderator of the intention-behaviour correlation (B = -.014, p < .001) and explained 24% of the between-study variance. This result remained unchanged when entered simultaneously with several control variables. The results of this analysis have important implications both for researchers and for intervention designers aiming to increase rates of PA.

Ectomycorrhizal fungi and past high CO2 atmospheres enhance mineral weathering through increased below-ground carbon-energy fluxes.

Field studies indicate an intensification of mineral weathering with advancement from arbuscular mycorrhizal (AM) to later-evolving ectomycorrhizal (EM) fungal partners of gymnosperm and angiosperm trees. We test the hypothesis that this intensification is driven by increasing photosynthate carbon allocation to mycorrhizal mycelial networks using 14CO2-tracer experiments with representative tree­fungus mycorrhizal partnerships. Trees were grown in either a simulated past CO2 atmosphere (1500 ppm)­under which EM fungi evolved­or near-current CO2 (450 ppm). We report a direct linkage between photosynthate-energy fluxes from trees to EM and AM mycorrhizal mycelium and rates of calcium silicate weathering. Calcium dissolution rates halved for both AM and EM trees as CO2 fell from 1500 to 450 ppm, but silicate weathering by AM trees at high CO2 approached rates for EM trees at near-current CO2. Our findings provide mechanistic insights into the involvement of EM-associating forest trees in strengthening biological feedbacks on the geochemical carbon cycle that regulate atmospheric CO2 over millions of years.

Acetazolamide in critically ill neonates and children with metabolic alkalosis.

BACKGROUND: Acetazolamide is an option for hypochloremic metabolic alkalosis, but there are limited reports in children. OBJECTIVE: To describe the acetazolamide regimen and outcomes in critically ill children with metabolic alkalosis. METHODS: This was a descriptive, retrospective study of patients <18 years of age who received ≥3 doses of acetazolamide for metabolic alkalosis (ie, pH > 7.45 and bicarbonate [HCO3] > 26 mEq/L). Patients receiving other treatments for metabolic alkalosis within 24 hours of acetazolamide were excluded. The primary objective was to identify the mean dose and duration of acetazolamide. Secondary objectives were to determine the number of patients with treatment success (ie, serum HCO3 22-26 mEq/L) and occurrence of adverse events. RESULTS: Thirty-four patients were included for analysis, the median age was 0.25 years (range = 0.05-12 years). The acetazolamide regimen included a mean dose of 4.98 ± 1.14 mg/kg for a mean number of 6.1 ± 5.3 (range = 3-24) doses. The majority (70.6%) received acetazolamide every 8 hours. Treatment success was achieved in 10 (29.4%) patients. Statistically significant differences were noted between the pre-acetazolamide and post-acetazolamide pH and HCO3, 7.51 ± 0.05 versus 7.37 ± 0.05 (P < .001) and 39.4 ± 6.1 mEq/L versus 31.4 ± 7.5 mEq/L (P < .001), respectively. CONCLUSIONS: This is the first study to evaluate acetazolamide dosing for metabolic alkalosis in children with and without cardiac disease. Acetazolamide treatment resulted in improved HCO3, but the majority of patients did not achieve our definition of treatment success. Future studies should elucidate the optimal acetazolamide regimen.

Renal Mass Found on Imaging of Spine for Back Pain: An Incidental Finding.

A middle-aged female patient who presented with back pain was found incidentally to have a renal mass by magnetic resonance imaging (MRI). Further imaging, including computerized tomography (CT) with contrast, suggested a high likelihood of malignancy. Following surgical resection, the tumor was found to be a rare benign lesion on subsequent pathological examination. The patient had conservative treatment for her presenting spine issues and is doing very well. Prompt work-up and treatment of incidental findings by the team of primary care, physical medicine and rehabilitation physicians, radiologists, pathologists, and surgeons helped to ensure a good outcome. Residents had a learning opportunity about the disease and on timely management of incidental findings.

Unexpected case of chagas disease reactivation in endomyocardial biopsy for evaluation of cardiac allograft rejection.

Acute Chagas disease reactivation (CDR) after cardiac transplantation is a well-known phenomenon in endemic countries of Central and South America and Mexico, but is rare outside of those countries. In this report, we describe a case of a 49-year-old male who presented 25 weeks after heart transplant with clinical features concerning for acute rejection, including malaise, anorexia, weight loss, and fever. His immunosuppression therapy included tacrolimus, mycophenolate, and prednisone. An endomyocardial biopsy revealed lymphocytic and eosinophilic inflammation, myocyte damage, and rare foci of intracellular organisms consistent with Trypanosoma cruzi amastigotes. The patient had no known history of Chagas disease. Upon additional questioning, the patient endorsed bites from reduviid bugs during childhood in El Salvador. Follow-up serum PCR testing was positive for T. cruzi DNA. Tests for other infectious organisms and donor specific antibodies were negative. This case illustrates the striking clinical and histologic similarities between acute cellular rejection and acute CDR with cardiac involvement in heart transplant patients, and thus emphasizes the importance of pre-transplant testing for Chagas in patients with epidemiologic risk factors.

Maladaptive Denial of Severe Pain and Acute Orthopedic Injuries in a Patient With a Schizoaffective Disorder.

Persistent denial of severe and acute pain following orthopedic injuries has not been previously reported. We present a case of a 24-year-old woman with a history of schizoaffective disorder who suffered severe pain secondary to acute orthopedic injuries who insisted, "I am fine! There is nothing wrong with me." Her maladaptive denial resulted in an initial refusal of necessary medical/surgical care, but she eventually accepted the necessary treatments despite her persistent belief she did not need such care. Her verbalizations and behaviors were characterized by active avoidance and angry reactions when a consulting psychiatrist spoke to her regarding her clinical condition. A modified version of the Conscious Avoidance subscale of the Denial of Illness Questionnaire was useful in measuring the severity level of her denial. This case report suggests that the behavioral features of psychological denial appear different from those associated impaired self-awareness secondary to an underlying brain disorder.

5HT6 Antagonists in the Treatment of Alzheimer's Dementia: Current Progress.

Alzheimer's disease is an important condition with a considerable and unmet disease burden in large need of continued research and more treatment options. The 5HT6 antagonists are a new class of medications to be offered. Because they are pro-cholinergic, these medications are to be used as adjuncts to acetylcholinesterase inhibitors (such as donepezil), further increasing acetylcholine in the central nervous system (CNS). Early trials of the 5HT6 antagonists showed improvements in cognition and activities of daily living when used as adjuncts to current therapies for Alzheimer's dementia. However, recent phase III trials have failed to show a statistically significant improvement in cognitive function. This article will provide a comprehensive review of 5HT6 antagonists in drug development, including some that have been recently discontinued. We will discuss both the successes and failures of this drug class and provide rationale for their continued research and development.

Digital image quantification of siderophores on agar plates.

This article presents visual image data and detailed methodology for the use of a new method for quantifying the exudation of siderophores during fungal growth. The data include images showing time series for calibration, fungal exudation, and negative controls, as well as replication accuracy information. In addition, we provide detailed protocols for making CAS assay layer plates, the digital analysis protocol for determining area of color change, and discuss growth media that do and do not work with the layer plate method. The results of these data, their interpretation, and further discussion can be found in Andrews et al., 2016 [1].

Layer plate CAS assay for the quantitation of siderophore production and determination of exudation patterns for fungi.

The chrome azurol S (CAS) assay measures the chelating activity of siderophores, but its application (especially to fungi) is limited by toxicity issues. In this note, we describe a modified version of the CAS assay that is suitable for quantifying siderophore exudation for microorganisms, including fungi.

Siderophore-promoted dissolution of chromium from hydroxide minerals.

Biomolecules have significant impacts on the fate and transport of contaminant metals in soils and natural waters. Siderophores, Fe(iii)-binding agents that are exuded by microbes and plants, may form strong complexes with and promote the dissolution of contaminant metal ions, such as Co(iii), U(iv), or Pu(iv). Although aqueous Cr(iii)-siderophore complexes have been recognized in the laboratory setting for almost 40 years, few studies have explored interactions of siderophores with Cr-bearing minerals or considered their impacts on environmental chemistry. To better understand the possible effects of siderophores on chromium mobility, we conducted a series of dissolution experiments to quantify the dissolution rates of Cr(iii)(OH)3 in the presence of hydroxamate, catecholate, and α-hydroxycarboxylate siderophores over a range of environmentally relevant pH values. At pH = 5, dissolution rates in the presence of siderophores are similar to control experiments, suggesting a predominantly proton-promoted dissolution mechanism. At pH = 8, the sorption of the siderophores desferrioxamine B and rhizoferrin can be modeled by using Langmuir isotherms. The dissolution rates for these siderophores are proportional to the surface concentrations of sorbed siderophore, and extended X-ray absorption fine structure spectra of dissolution products indicates the formation of Cr(iii)HDFOB(+) and Cr(iii)rhizoferrin(3-) complexes, suggesting a ligand-promoted dissolution mechanism at alkaline pH. Because siderophores promote Cr(iii)(OH)3 dissolution at rates similar in magnitude to those of iron hydroxides and the resulting Cr(iii)-siderophore complexes may be persistent in solution, siderophores could potentially contribute to the mobilization of Cr in soils and sediments where it is abundant due to geological or anthropogenic sources.

Implementation of a bowel regimen protocol in critically ill children: A pilot study.

No studies have evaluated the outcomes of a bowel regimen (BR) in critically ill children receiving enteral nutrition. In fall 2010, a comprehensive feeding protocol and BR protocol were initiated in our institution. Six age-based BR protocols were developed, each of which included a four-step approach. This retrospective study evaluated children <18 years of age who received the BR between July 18, 2010 and April 31, 2012. The primary objective was to determine the percentage of patients requiring BR escalation beyond the initial step in the protocol (Step 1). Secondary objectives included the number of patients with a protocol deviation and the frequency of adverse events. Fifty-four patients were included. The majority were male with a median age of 0.25-year-old (range 0.08-15 yr). Forty-three (79.6%) patients received opioid continuous infusions. The BR was initiated on pediatric intensive care unit day 1 (range 1-25 d). Thirty patients (55.6%) required escalation beyond "Step 1". All patients who received "Step 2" and "Step 3" had a protocol deviation. Opioid duration was significantly associated with protocol escalation (odds ratio, 0.83; 95% confidence interval 0.689-0.997; P = 0.047). This pilot study is the first to describe the outcomes of the implementation of a four-step BR in critically ill children. Future studies should focus on the optimal regimen to alleviate constipation in critically ill children.

Once-daily amoxicillin for pharyngitis.

A once-daily antibiotic regimen for group A ß-hemolytic streptococcal pharyngitis (GABHS) could improve compliance and be effective in the prevention of rheumatic fever, a dangerous complication of untreated or poorly treated GABHS. Amoxicillin is ideal for once-daily dosing due to its low cost. Azithromycin, cefadroxil, ceftibuten, cefixime and extended release amoxicillin are also FDA approved to treat GABHS once daily; however, even when taken for short courses, these antibiotics are more expensive compared with a oncedaily dosing of conventional amoxicillin for 10 days. The American Heart Association recently recommended once-daily amoxicillin dosing when treating GABHS, and amoxicillin has been proven to be effective when dosed once daily, with no obvious disadvantage compared with twice-daily dosing or with conventional penicillin treatment 3 to 4 times daily.

Modafinil treatment of opioid-induced sedation.

STUDY OBJECTIVE: The purpose of this study was to assess the efficacy of modafinil in combating opioid-induced sedation. DESIGN: A 1-year retrospective chart review of all patients receiving modafinil, a wake-promoting agent, to treat opioid-induced sedation. Opioid-induced sedation was measured using Epworth Sleepiness Scale (ESS). SETTING: Outpatient, private practice. PATIENTS: Eleven adult patients, six female and five male, being treated with opioids for chronic, nonmalignant pain. RESULTS: A significant decrease was observed between pretreatment and posttreatment ESS measurements during modafinil treatment. CONCLUSION: The results suggest an improvement in opioid-induced sedation in patients treated for nonmalignant pain.