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Παρασκευή 29 Ιουνίου 2018

Ayurveda metallic-mineral 'Bhasma-associated severe liver injury

Ayurveda Bhasma is a metallic-mineral preparation homogenised with herbal juices or decoctions and modified with heat treatment to apparently detoxify the heavy metals. It is widely recommended for the treatment of many disease conditions by practitioners of complementary and alternative medicine in the absence of good quality clinical trial evidence on its safety and efficacy. Heavy metal-induced liver injury is widely reported in the literature, and heavy metal adulteration of non-Bhasma-related Ayurveda and herbal products has been well described. We report a patient who developed severe liver injury requiring listing for liver transplantation for improved survival, after consumption of Bhasma for dyspepsia. This case describes the first documented case and toxicology analysis of Ayurveda Bhasma associated with severe drug-induced liver injury. Physicians must be alert regarding patient's use of supposedly safe Ayurveda Bhasma that may promote acute severe liver injury in the absence of other known aetiologies.



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Phytobezoar and duodenal ulcer as complication of Duodopa therapy in a patient affected by Parkinsons disease

Continuous duodenal infusion of levodopa/carbidopa intestinal gel (LCIG) is an established treatment to control motor fluctuations in Parkinson's disease. Duodenal infusion allows a steady absorption of the drug in the small bowel, reducing plasmatic fluctuations of levodopa. Some complications may occur during the treatment, often related to intrajejunal percutaneous endoscopic gastrostomy (PEG-J). We report a case of duodenal ulcer associated with a phytobezoar involving the end of jejunal probe, in a patient who underwent PEG-J for LCIG infusion. In the last 2 weeks, the patient suffered from abdominal pain and dyspepsia. Oesophagogastroduodenoscopy showed an ulcerative lesion of the duodenum due to traction of the jejunal tube; the end of the jejunal tube was wrapped in a phytobezoar. This case is interesting because of the extension of the ulcerative lesion due to PEG-J dislocation and because of the subtle symptoms associated with it.



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Just another case of bacterial meningitis... or... is it?

Non-traumatic cerebrospinal fluid (CSF) rhinorrhoea is a rare condition. We describe a case of a 62-year-old woman with pneumococcal bacterial meningitis who later was found to have CSF rhinorrhoea secondary to an eroding skull base tumour, which was proven to be pituitary macroadenoma on biopsy. She recovered well from meningitis without any neurological sequelae and underwent trans-sphenoidal surgery for tumour removal as well as dural repair.



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Ectopic insulinomas in the pelvis secondary to rectum neuroendocrine tumour

We describe a middle-aged woman with recurrent hypoglycaemia, who confirmed with rectum G1 neuroendocrine tumour (NET) 6 years ago. Biochemical assay showed high concentration of serum insulin and C-peptide associated with hypoglycaemia. Because of recurrent hypoglycaemia in June 2015, she underwent a resection of the tail of the pancreas. However, hypoglycaemia attack happened more frequently and severely. 68Ga-DOTA-NOC positron emission tomography/CT revealed five foci in the pelvis with intense uptake. Immediately after excision of the pelvic lesions, insulin and C-peptide decreased to normal levels promptly, and therefore, serum glucose increased significantly. Hypoglycaemia was disappeared, and insulin and C-peptide were normal at 2 years follow-up after surgery. Immunohistochemistry validated the primary rectum NET and pelvic tumours expressed with higher insulin, somatostatin receptor and glucagon-like peptide-1. This is the first reported ectopic pelvic insulinomas secondary to rectum NET, which may originate both from neuroendocrine cells in the rectum and pelvic tissues.



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Pineal gland apoplexy mimicking as migraine-like headache

Description 

A 24-year-old female patient presented with acute-onset, vertex headache associated with photophobia, nausea and vomiting. Initially, the headache was mild (pain scale 4/10), but over the next 4–5 hours, the severity of the headache increased to pain scale of 8/10. She had a history of similar headaches of lesser intensity in the past. There was also a strong family history of migraine. Her mother and younger sister used to get similar headaches and got relieved with antimigraine medications. Exact details of her medication history were unavailable since the progression of severity of her headache was gradual. This was unlike thunderclap headache and, in high likelihood, another episode of migraine.

Her vitals were stable. Neurological examination, including funduscopy, was grossly normal

On radiological evaluation, the MRI brain showed T1-weighted hyperintense pineal gland, as seen on the axial view suggestive of intrapineal gland apoplexy (figure 1). The fluid–fluid interface is depicted by the horizontal...



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Unusual cause of elbow pain in a baseball pitcher

An adolescent, right hand-dominant, baseball pitcher presented to sports medicine clinic with posterolateral right elbow pain over 4 months. He rated his pain as 8/10 with pitching, especially at the late cocking phase of throwing. Prior to consult, he had rested 3 months from pitching, progressing to strengthening exercises, with no pain relief. On physical examination, he had 120° of active external rotation, 80° of active internal rotation, mild tenderness to palpation over the capitellum and normal elbow radiography. Magnetic resonance arthrogram of the right elbow revealed subtle, posterolateral joint capsular tear and adjacent synovial hypertrophy. The patient was diagnosed with elbow synovial fold syndrome that was causing impingement at the radiocapitellar joint and was referred to an orthopaedic surgeon. Arthroscopy revealed redundant tissue; scar formation at the radiocapitellar joint was debrided. The patient participated in physical therapy for 2 months and was able to start throwing 3 months later.



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Double tongue signs in a case of submandibular space infection

Description

Double tongue signs are a unique physical finding which involve an elevation of floor of the oropharynx caused by a bilateral infection of the submandibular space (a well-known example is Ludwig's angina) (figure 1A).1 2 In this case, an 80-year-old woman with a 10-year history of diabetes mellitus was referred to our emergency department. She presented with swelling from the submandibular region to the neck surface, with a 3-day history of continuous fever, weakness and fatigue. Physical examination revealed neck oedema with erythema and tenderness (figure 1B), without lymphadenopathy. The floor of the oropharynx was clearly swollen and elevated, such that it appeared to be a double tongue; this was erythematous and tender. Enhanced CT of the neck was performed, which revealed bilateral fluid retention with swollen surrounding soft tissues in the submandibular space (figure 2). We...



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Early-stage right temporal lobe variant of frontotemporal dementia: 3 years of follow-up observations

The right temporal lobe variant of frontotemporal dementia (FTD) is an uncommon progressive neurodegenerative disorder. We present the case of a 77-year-old right-handed man who presented with altered behaviour and problems with interpersonal relationships. He had no decline in cognitive function but brain perfusion single-photon emission CT demonstrated distinct hypoperfusion in the right temporal pole. At 2-year follow-up, he could not recognise his wife's relatives; and at 3-year follow-up, he had semantic aphasia. Decreased brain perfusion extended from the right temporal lobe into the contralateral temporal and both frontal lobes. These findings suggest that the right temporal lobe variant of FTD should be considered in elderly patients with altered behaviour and problems with interpersonal relationships, even if dementia is not suspected. The right anterior temporal lobe may play a key role in the onset of the early symptoms of this disease.



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Pseudo-Wellens syndrome secondary to concurrent cannabis and phencyclidine intoxication

Wellens' syndrome is an electrocardiographic pattern of T-wave changes associated with critical stenosis of the proximal left anterior descending artery, signifying imminent risk of an anterior-wall myocardial infarction. The Wellens' electrocardiographic pattern can also be noted in several cardiac and non-cardiac diseases. We chronicle here a unique case of a patient who presented with atypical left chest pain and dizziness for 6 hours. His pain started after he smoked phencyclidine-laced cannabis. Cardiac panel demonstrated normal troponin T levels. Electrocardiogram showed sinus rhythm with new deep biphasic T-wave inversions in anterolateral leads. Coronary angiography showed no pathological processes. Subsequently, ECG changes resolved coincidentally with the resolution of chest pain. He was eventually diagnosed with pseudo-Wellens' syndrome. This paper illustrates that physicians should be vigilant for Wellens' syndrome mimicked by acute phencyclidine and cannabis intoxication. Additionally, we present a review of various aetiologies of pseudo-Wellens' syndrome, especially in patients with substance abuse.



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Suction-induced retinopathy: optical coherence tomography correlations

We report a clinical case of a teenager whose eyes were exposed to highly negative suction pressures for brief seconds. The patient presented with a bilateral cystoid macular oedema associated with a thickening of outer nuclear layer evidenced by optical coherence tomography. The patient's constellation of findings is most easily explained by the abrupt expansion and traction of a cohesive vitreous base onto the retinal layers.



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Inflammatory myofibroblastic tumour: a rare cause of central airway obstruction

Description

A 70-year-old woman with no comorbidities presented with cough, wheezing, exertional dyspnoea and a sensation of throat fullness. She never smoked and was recently diagnosed with asthma based on a normal chest radiograph and pulmonary function testing but failed to improve with bronchodilators and steroids. Her initial chest radiograph was unremarkable, and spirometry suggested a fixed intrathoracic obstruction. CT of the chest obtained after 2 months showed an irregular density in the trachea, 1.4x1.7 cm (figure 1). Flexible bronchoscopy showed a polypoid mass 2–3 cm above the carina adherent to the right wall of the trachea (figure 2). Rigid bronchoscopy with neodymium-doped yttrium aluminium garnet (Nd:YAG) laser photoresection was performed. Given the vascular nature of the tumour, removal was complicated by significant bleeding, which required endobronchial epinephrine and laser coagulation. The patient recovered without further complications. Immunohistochemical staining on the excised tumour was positive for vimentin...



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Second look at Streptococcus sanguinis and the colon

Although the link between Streptococcus bovis bacteraemia and colon cancer is well established, bacteraemia from other viridans group streptococci that commonly colonise colonic mucosa may also herald occult malignancy. We present a case of Streptococcus sanguinis bacteraemia in an elderly man with new anaemia that led to the detection and removal of a high-grade colon neoplasm. This case contributes to a growing body of literature contending that unexplained streptococcal bacteraemia merits a thorough workup that may include relatively invasive procedures such as endoscopy. Diagnostic colonoscopy provides an opportunity to prevent invasive malignancy that may outweigh bleeding and perforation risks in elderly patients.



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Atypical presentation of type B aortic dissection mimicking appendicitis managed medically

This is a case of a 53-year-old male patient with a history of hypertension who developed sudden onset of right lower quadrant pain. On arrival, chest X-ray showed prominent aortic arch without cardiomegaly. CT of the abdomen/pelvis showed aortic dissection in descending aorta without rupture. CT of the chest displayed sparing of ascending and aortic arch. Ultrasound Doppler of the kidney displayed mild renal artery stenosis. Differential diagnosis was acute appendicitis, acute ureteric and severe gastroenteritis. The patient was started on oral blood pressure (BP) medicine to titrate off intravenous nicardipine and esmolol drip. After 10 days, he was switched to oral BP medicine. His leg pain was resolved with normal palpable pulse. One week later, his kidney function worsened. Thus, Lasix and minoxidil were stopped. The patient had no chest/abdominal pain and was tolerating the medicine well during his 2-week follow-up. Acute aortic dissection can be a fatal clinical emergency. Timing is critical during diagnosis and management of patients.



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EBV colitis with ulcerative colitis: a double whammy

We report this case of a 21-year-old immunocompetent man presenting with ulcerative colitis and superimposed Epstein-Barr virus (EBV) colitis. He presented for the first time with symptoms of blood-mixed diarrhoea and raised inflammatory markers. His endoscopic and histological appearances were found to be due to ulcerative colitis for which he was started on standard therapy with intravenous steroids. In spite of this, he continued to be symptomatic and his inflammatory markers continued to rise. A virology screen done showed evidence of previous EBV infection, and in view of poor response to immunosuppression, a superimposed infection was suspected. EBV DNA PCR done on colonic biopsies was found to be positive and the patient was started on intravenous ganciclovir to which he responded well. This case highlights the importance of considering a superimposed infection in patients with poor initial response to steroid therapy in inflammatory bowel disease.



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Adult-onset epileptic aphasia

Aphasia is a language disorder characterised by loss of ability to produce or comprehend written or spoken language. In majority of the cases, it is due to stroke. Aphasia may also present as an ictal or postictal state of temporal or frontal lobe seizures. Nevertheless, its isolated occurrence in individuals without a clear-cut history of seizures raises diagnostic difficulties with important therapeutic implications.

A case of epileptic aphasia is reported in which the diagnosis was confirmed by electroencephalogram with a dramatic therapeutic response to an antiepileptic drug.



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Reversible cardiac dysfunction in long-standing hypertension may be global variant of stress cardiomyopathy

An adult man with long-standing poorly controlled cardiac risk factors presented with acute decompensated heart failure (ADHF). Echocardiogram, cardiac MRI and catheterisation suggested idiopathic dilated cardiomyopathy, severe systolic dysfunction, ejection fraction 25% with global left ventricular (LV) dilation and apical thrombus. He responded well to diuretics and gradual uptitration of lisinopril and carvedilol. Follow-up echocardiogram in 2 months demonstrated complete recovery of systolic function, normalisation of LV size and shape with severe LV hypertrophy. This presentation is potentially a global variant of stress cardiomyopathy with recovery of LV function, highlighting the importance of appropriate imaging, catheterisation and clinical monitoring in patients with ADHF.



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Anomalous aortic origin of a coronary artery with an intraseptal course: novel techniques in haemodynamic assessment

Description

A 7-year-old boy presented to the emergency room after an episode of syncope while at home. Although, it was non-exertional, it lasted 2 min and was preceded by angina-like chest pain. Vitals, physical examination, chest radiograph and ECG were normal. Subsequent cardiology evaluation led to an echocardiogram that showed anomalous origin of the left main coronary artery from the opposite sinus of Valsalva with adjacent ostia which was confirmed on CT angiography. In addition, it showed a long 2.5–3 cm deep intraseptal course of the left anterior descending (LAD) and short intraseptal course of the left circumflex (LCX) artery. Stress nuclear perfusion scan and Holter monitoring were negative, but stress cardiac MRI showed an inducible perfusion defect along the anterior interventricular septal wall most prominent at the mid-ventricular and basilar levels. Coronary angiography (figure 1 and video 1) and intravascular ultrasound demonstrated significant systolic compression of the intraseptal segment...



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Biots breathing associated with acute bacterial meningitis in a child

Description

A 19-month-old boy presented to the emergency room of our hospital with fever and drowsiness following asymmetric focal seizure. On examination the patient was somnolent, had signs of meningeal irritation and intermittent nystagmus. Laboratory examination revealed increased C-reactive protein (200 mg/L), procalcitonin (25.9 ng/mL) and hyponatraemia (132 mEq/L). The initial CT of the brain was normal. Given presumed meningoencephalitis, intravenous dexamethasone, vancomycin, ceftriaxone and acyclovir treatment was started, and the child was admitted to the paediatric intensive care unit. Several hours after the admission, irregular, jerky respirations appeared, consistent with Biot's breathing (figure 1). The patient developed hypertension (129/90 mm Hg) and relative bradycardia (90 bpm). Due to these signs, consistent with increased intracranial pressure, lumbar puncture was deferred and the child received mannitol with notable improvement in his condition. On hospital day 2, lumbar puncture revealed turbid fluid with an opening pressure of 5 cmH2O, white blood cells...



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Subfoveal congenital hypertrophy of retinal pigment epithelium

Description

A 25-year-old man presented with slight blurring of vision in the right eye (RE), noted 3 years ago. There was no positive systemic history. His best corrected visual acuity was 6/9 in RE and 6/6 in the left eye (LE) at presentation. Anterior segment evaluation was unremarkable in both eyes with normal pupil light reflexes. Fundus evaluation revealed a flat circular lesion beneath the fovea, and was measured to be one-third of the size of the optic nerve head. It was a densely pigmented lesion, black in colour, with a surrounding depigmented whitish halo (figure 1). The LE was within normal range on clinical examination. Spectral domain optical coherence tomography (SD-OCT) of RE revealed the lesion to be irregular but flat with hyper-reflectivity at the level of the retinal pigment epithelium (RPE). Discontinuity of the ellipsoid zone was noted to be overlying some parts of the lesion. These findings were also accompanied...



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A case of massive haemoptysis

Description

A 77-year-old female never-smoker presented with massive haemoptysis. Admission plain chest radiograph was normal.

She was haemodynamically stable on presentation but the following morning she had a further large-volume haemoptysis (>500 mL), resulting in respiratory arrest. Following resuscitation, haemoglobin fell from 94 to 66 g/dL. CT angiogram was performed (figure 1).

Figure 1

Sagittal CT angiogram, performed once the patient was stabilised.

She had previously been investigated for small volume haemoptysis and left upper lobe mass-like consolidation, which had fully resolved following a course of antibiotics. Recent bronchoscopy was normal, with no pathological organisms. There was no evidence of malignancy or connective tissue disease, and there was no additional past medical history. CT imaging had been reviewed at a thoracic oncology multi-disciplinary meeting and the previous episode was attributed to non-specific infection.

Question

What is the diagnosis (see figure 1)?

(A) Pulmonary artery...



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Childhood Craniopharyngioma: A 22-Year Challenging Follow-Up in a Single Center

Horm Metab Res
DOI: 10.1055/a-0641-5956

Craniopharyngioma is a sellar/suprasellar benign tumor whose aggressiveness may imply in endocrine disturbances (hypothalamic obesity and hormone deficiencies). Fifty-seven patients were evaluated according to clinical characteristics, hypothalamic involvement, type of treatment, anthropometric variables, adiposity indexes (body mass index Z score category at diagnosis and post-treatment, total body fat, visceral adipose tissue, and metabolic syndrome components) and analyzed through multiple regression and logistic models. Patients were stratified according to growth hormone deficiency and recombinant human growth hormone use. Mean ages at diagnosis and at study evaluation were 9.6 and 16.6 years old, respectively. A set of 43/57 (75.4%) patients presented with important hypothalamic involvement, 24/57 (42.1%) received surgical treatment and cranial radiotherapy, and 8/57 (14%) interferon-α exclusively. Fifty-five patients (96.5%) were considered growth hormone deficient, and 26/57 (45.6%) grew despite no recombinant human growth hormone replacement therapy. At diagnosis, 12/57 (21%) patients were obese, and 33/57 (57.9%) at study evaluation, and after 3.2 years (median) post first therapy. There was no influence of height Z score on body mass index Z score. Body mass index Z score at diagnosis positively influenced body mass index Z score, total body fat, waist circumference and the presence of the metabolic syndrome post-treatment. Replacement of recombinant human growth hormone decreased total body fat and visceral adipose tissue. Craniopharyngioma patients worsened body mass index Z score category 3.2 years (median) after first treatment. Body mass index Z score increased due to real weight gain, without height decrease. Replacement of recombinant human growth hormone had beneficial effect on adiposity.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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FDA Approves Novel Device for Treating Breathing Difficulty from Severe Emphysema

June 29, 2018 -- The U.S. Food and Drug Administration today approved a new device, the Zephyr Endobronchial Valve (Zephyr Valve), intended to treat breathing difficulty associated with severe emphysema. "Treatment options are limited for...

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Metabolic Disorders and Critically Ill Patients

No abstract available

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Epidural Analgesia and Subcutaneous Heparin 3 Times Daily in Cancer Patients With Acute Postoperative Pain

The use of epidural analgesia in conjunction with subcutaneous administration of unfractionated heparin 3 times per day could increase the risk of spinal epidural hematoma, but insufficient patient experience data exist to determine this. We retrospectively reviewed the incidence of spinal epidural hematoma in 3705 cases at our institution over a 7-year period of patients receiving acute postoperative epidural analgesia and heparin 3 times per day. No cases of spinal epidural hematoma were reported (95% CI, 0–0.0009952). Accepted for publication May 23, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Jackson Su, MD, Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Unit 409, 1515 Holcombe Blvd, Houston, TX 77030. Address e-mail to jsu@mdanderson.org. © 2018 International Anesthesia Research Society

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Proceedings From the Society for Advancement of Blood Management Annual Meeting 2017: Management Dilemmas of the Surgical Patient—When Blood Is Not an Option

Vigilance is essential in the perioperative period. When blood is not an option for the patient, especially in a procedure/surgery that normally holds a risk for blood transfusion, complexity is added to the management. Current technology and knowledge has made avoidance of blood transfusion a realistic option but it does require a concerted patient-centered effort from the perioperative team. In this article, we provide suggestions for a successful, safe, and bloodless journey for patients. The approaches include preoperative optimization as well as intraoperative and postoperative techniques to reduce blood loss, and also introduces current innovative substitutes for transfusions. This article also assists in considering and maneuvering through the legal and ethical systems to respect patients' beliefs and ensuring their safety. Accepted for publication April 20, 2018. Funding:None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Gee Mei Tan, MMED, MBBS, Department of Anesthesiology, University of Colorado, School of Medicine, 13123 E 16th Ave, B090, Aurora, CO 80045. Address e-mail to Geemei.tan@childrenscolorado.org. © 2018 International Anesthesia Research Society

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Prospective Observational Investigation of Capnography and Pulse Oximetry Monitoring After Cesarean Delivery With Intrathecal Morphine

BACKGROUND: Intrathecal morphine provides excellent analgesia after cesarean delivery; however, respiratory events such as apnea, bradypnea, and hypoxemia have been reported. The primary study aim was to estimate the number of apneas per subject, termed "apnea alert events" (AAEs) defined by no breath for 30–120 seconds, using continuous capnography in women who underwent cesarean delivery. METHODS: We performed a prospective, observational study with institutional review board approval of women who underwent cesarean delivery with spinal anesthesia containing 150-µg intrathecal morphine. A STOP-Bang obstructive sleep apnea assessment was administered to all women. Women were requested to use continuous capnography and pulse oximetry for 24 hours after cesarean delivery. Nasal sampling cannula measured end-tidal carbon dioxide (EtCO2) and respiratory rate (RR), and oxygen saturation (SpO2) as measured by pulse oximetry. Capnography data were defined as "valid" when EtCO2 >10 mm Hg, RR >5 breaths per minute (bpm), SpO2 >70%, or during apnea (AAE) defined as "no breath" (EtCO2, 30 kg/m2/weight >90 kg, and 11% with suspected obstructive sleep apnea (known or STOP-Bang score >3). The duration of normal capnography and pulse oximetry data was mean (SD) (range) 8:28 (7:51) (0:00–22:32) and 15:08 (6:42) (1:31–23:07) hours:minutes, respectively; 6 women did not use the capnography. There were 198 AAEs, mean (SD) duration 57 (27) seconds experienced by 39/74 (53%) women, median (95% confidence interval for median) (range) 1 (0–1) (0–29) per subject. Observation of RR by nurses was ≥14 bpm at all time-points for all women, r = 0.05 between capnography and nurse RR (95% confidence interval, −0.04 to 0.14). There were no clinically relevant adverse events for any woman. Sixty-five women (82%) had complaints with the capnography device, including itchy nose, nausea, interference with nursing baby, and overall inconvenience. CONCLUSIONS: We report 198 AAEs detected by capnography among women who underwent cesarean delivery after receiving intrathecal morphine. These apneas were not confirmed by the intermittent hourly nursing observations. Absence of observer verification precludes distinction between real, albeit nonclinically significant alerts with capnography versus false apneas. Discomfort with the nasal sampling cannula and frequent alerts may impact capnography application after cesarean delivery. No clinically relevant adverse events occurred. Accepted for publication April 26, 2018. Funding: This study was supported by an Investigator Research Grant (VT ID# ISR-2013–10323) from Medtronic, which provided financial support and the capnography equipment. The funding body had no role in the study design, raw data extraction and processing, data analysis or interpretation, writing of the manuscript, or manuscript submission for publication. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). This study was conducted at the Lucile Packard Children's Hospital, Stanford, California. Clinical trial number: clinicaltrials.gov (NCT02417038; April 10, 2015). Institutional review board: Shana Stolarczyk, Research Compliance Office, Stanford University, 3000 El Camino Real, Five Palo Alto Sq, 4th Floor, Palo Alto, CA 94306. E-mail: irbeducation@lists.stanford.edu; Shana.Stolarczyk@stanford.edu. Reprints will not be available from the authors. Address correspondence to Carolyn F. Weiniger, MBChB, Division of Anesthesia, Critical Care and Pain, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Address e-mail to carolynfweiniger@gmail.com. © 2018 International Anesthesia Research Society

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Opioids for Acute Pain Management in Patients With Obstructive Sleep Apnea: A Systematic Review

The intrinsic nature of opioids to suppress respiratory function is of particular concern among patients with obstructive sleep apnea (OSA). The association of OSA with increased perioperative risk has raised the question of whether patients with OSA are at higher risk for opioid-induced respiratory depression (OIRD) compared to the general population. The aims of this systematic review were to summarize current evidence with respect to perioperative OIRD, changes in sleep-disordered breathing, and alterations in pain and opioid sensitivity in patients with OSA. A systematic literature search of studies published between 1946 and October 2017 was performed utilizing the following databases: Medline, ePub Ahead of Print/Medline In-process, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed—NOT-Medline and ClinicalTrials.Gov. Of 4321 initial studies, 40 met the inclusion criteria. The Oxford level of evidence was assessed. Overall, high-quality evidence on the comparative impact of acute opioid analgesia in OSA versus non-OSA patients is lacking. The current body of evidence is burdened by significant limitations including risk of bias and large heterogeneity among studies with regard to OSA severity, perioperative settings, outcome definitions, and the presence or absence of various perioperative drivers. These factors complicate an accurate interpretation and robust analysis of the true complication risk. Nevertheless, there is some consistency among studies with regard to a detrimental effect of opioids in the presence of OSA. Notably, the initial 24 hours after opioid administration appear to be most critical with regard to life-threatening OIRD. Further, OSA-related increased pain perception and enhanced opioid sensitivity could predispose patients with OSA to a higher risk for OIRD without overdosing. While high-quality evidence is needed, retrospective analyses indicate that critical, life-threatening OIRD may be preventable with a more cautious approach to opioid use, including adequate monitoring. Accepted for publication May 8, 2018. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Stavros G. Memtsoudis, MD, PhD, Departments of Anesthesiology, Critical Care, and Pain Management and Public Health, Hospital for Special Surgery, Weill Cornell Medical College, 535 E 70th St, New York, NY 10021. Address e-mail to memtsoudiss@hss.edu. © 2018 International Anesthesia Research Society

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Practice of Ultrasound-Guided Palpation of Neck Landmarks Improves Accuracy of External Palpation of the Cricothyroid Membrane

BACKGROUND: Ultrasonography can accurately identify the cricothyroid membrane; however, its impact on the subsequent accuracy of external palpation is not known. In this study, we tested the ability of anesthesia participants to identify the midpoint of the cricothyroid membrane using external palpation with and without ultrasound (US)-guided practice. METHODS: Following institutional ethics approval and informed consent, anesthesia participants consisting of anesthesia residents, fellows, and practicing anesthesia assistants underwent didactic teaching on neck landmarks. The participants were then randomized to practice palpation of neck landmarks with US guidance (US group) or without ultrasonography (non-US [NUS] group). After the practice session, each participant identified the cricothyroid membrane using external palpation on the neck of 10 volunteers and marked the anticipated entry point for device insertion (palpation point [PT]). The midpoint of the cricothyroid membrane of each volunteer had been premarked with invisible ink using ultrasonography (US point) by a separate member of the research team. The primary outcome was the accuracy rate defined as the percentage of the attempts with the distance ≤5 mm measured from the PT to US point for the participant. The primary outcome was compared between NUS and US groups using Wilcoxon rank sum test. A mixed-effect logistic regression or mixed-effect linear model was also conducted for outcomes accounting for the clustering and adjusting for potential confounders. RESULTS: Fifteen anesthesia participants were randomized to US (n = 8) and NUS (n = 7) groups. A total of 80 and 61 attempts were performed by the US and NUS groups, respectively. The median accuracy rate in the US group was higher than the NUS group (65% vs 30%; P = .025), and the median PT-US distance in the US group was shorter than in the NUS group (4.0 vs 8.0 mm; P = .04). The adjusted mean PT-US distance in the US group was shorter compared to the NUS group (adjusted mean [95% CI], 3.6 [2.9–4.6] vs 6.8 [5.2–8.9] mm; P

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Dexmedetomidine Versus Remifentanil for Monitored Anesthesia Care During Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A Randomized Controlled Trial

BACKGROUND: We hypothesized that, compared to remifentanil, dexmedetomidine used for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) performed under monitored anesthesia care (MAC) in nonintubated patients would result in fewer episodes of major respiratory adverse events (number of episodes of bradypnea, apnea or desaturation) but no difference in satisfaction with perioperative conditions. METHODS: Sixty (American Society of Anesthesiologists physical status I–III) patients scheduled to undergo EBUS-TBNA under MAC were randomized to receive either remifentanil (0.5 µg/kg IV bolus) in 10 minutes, followed by 0.05–0.25 µg/kg/min, or dexmedetomidine (0.4 µg/kg IV bolus) in 10 minutes, followed by 0.5–1.0 µg/kg/h. The primary outcome was the number of major respiratory adverse events (bradypnea, apnea, or hypoxia). The secondary outcomes included hemodynamic variables, discharge time from the postanesthesia care unit, endotracheal lidocaine use, patient's sedation using the Observer Assessment of Alertness/Sedation Scale, operative conditions, operator and patient satisfaction, pain, coughing, vocal cord mobility, recall, and nausea/vomiting. RESULTS: Dexmedetomidine produced significantly fewer episodes of major respiratory events (bradypnea, apnea, or desaturation), with 0 [0–0.5] episodes versus 2 [0–5] (median [interquartile range]) (P = .001), than did remifentanil. Fewer episodes of bradypnea or apnea (dexmedetomidine: 0 [0–0] versus remifentanil: 0 [0–0.5]; P = .031), and fewer episodes of desaturation (dexmedetomidine: 0 [0–0.5] versus remifentanil: 1 [0–4]; P = .039) were recorded in the dexmedetomidine group. The time needed for patients to meet postanesthesia care unit discharge criteria (Aldrete score: 9) after EBUS-TBNA was longer in the dexmedetomidine group (10 [3–37.5] minutes) versus the remifentanil group (3 [3–5] minutes) (P

https://ift.tt/2IEIDiC

Potent Inactivation-Dependent Inhibition of Adult and Neonatal NaV1.5 Channels by Lidocaine and Levobupivacaine

BACKGROUND: Cardiotoxic effects of local anesthetics (LAs) involve inhibition of NaV1.5 voltage-gated Na+ channels. Metastatic breast and colon cancer cells also express NaV1.5, predominantly the neonatal splice variant (nNaV1.5) and their inhibition by LAs reduces invasion and migration. It may be advantageous to target cancer cells while sparing cardiac function through selective blockade of nNaV1.5 and/or by preferentially affecting inactivated NaV1.5, which predominate in cancer cells. We tested the hypotheses that lidocaine and levobupivacaine differentially affect (1) adult (aNaV1.5) and nNaV1.5 and (2) the resting and inactivated states of NaV1.5. METHODS: The whole-cell voltage-clamp technique was used to evaluate the actions of lidocaine and levobupivacaine on recombinant NaV1.5 channels expressed in HEK-293 cells. Cells were transiently transfected with cDNAs encoding either aNaV1.5 or nNaV1.5. Voltage protocols were applied to determine depolarizing potentials that either activated or inactivated 50% of maximum conductance (V½ activation and V½ inactivation, respectively). RESULTS: Lidocaine and levobupivacaine potently inhibited aNaV1.5 (IC50 mean [SD]: 20 [22] and 1 [0.6] µM, respectively) and nNaV1.5 (IC50 mean [SD]: 17 [10] and 3 [1.6] µM, respectively) at a holding potential of −80 mV. IC50s differed significantly between lidocaine and levobupivacaine with no influence of splice variant. Levobupivacaine induced a statistically significant depolarizing shift in the V½ activation for aNaV1.5 (mean [SD] from −32 [4.6] mV to −26 [8.1] mV) but had no effect on the voltage dependence of activation of nNaV1.5. Lidocaine had no effect on V½ activation of either variant but caused a significantly greater depression of maximum current mediated by nNaV1.5 compared to aNaV1.5. Similar statistically significant shifts in the V½ inactivation (approximately −10 mV) occurred for both LAs and NaV1.5 variants. Levobupivacaine (1 µM) caused a significantly greater slowing of recovery from inactivation of both variants than did lidocaine (10 µM). Both LAs caused approximately 50% tonic inhibition of aNaV1.5 or nNaV1.5 when holding at −80 mV. Neither LA caused tonic block at a holding potential of either −90 or −120 mV, voltages at which there was little steady-state inactivation. Higher concentrations of either lidocaine (300 µM) or levobupivacaine (100 µM) caused significantly more tonic block at −120 mV. CONCLUSIONS: These data demonstrate that low concentrations of the LAs exhibit inactivation-dependent block of NaV1.5, which may provide a rationale for their use to safely inhibit migration and invasion by metastatic cancer cells without cardiotoxicity. Accepted for publication May 21, 2018. Funding: This study was supported by a BJA/RCoA grant awarded to T.G.H. via the National Institute of Academic Anaesthesia, UK. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). T. Elajnaf and D. T. Baptista-Hon contributed equally and share first authorship. Reprints will not be available from the authors. Address correspondence to Tim G. Hales, PhD, The Institute of Academic Anaesthesia, Division of Neuroscience, School of Medicine, Ninewells Hospital, University of Dundee, Dundee DD1 9SY, United Kingdom. Address e-mail to t.g.hales@dundee.ac.uk. © 2018 International Anesthesia Research Society

https://ift.tt/2tG4IZo

Monitoring Depth of Hypnosis: Mid-Latency Auditory Evoked Potentials Derived aepEX in Children Receiving Desflurane-Remifentanil Anesthesia

BACKGROUND: The aepEXplus monitoring system, which uses mid-latency auditory evoked potentials to measure depth of hypnosis, was evaluated in pediatric patients receiving desflurane-remifentanil anesthesia. METHODS: Seventy-five patients, 1–18 years of age (stratified for age; 1–3, 3–6, 6–18 years, for subgroup analyses), were included in this prospective observational study. The aepEX and the bispectral index (BIS) were recorded simultaneously, the latter serving as a reference. The ability of the aepEX to detect different levels of consciousness, defined according to the University of Michigan Sedation Scale, investigated using prediction probability (Pk), and receiver operating characteristic (ROC) analysis, served as the primary outcome parameter. As a secondary outcome parameter, the relationship between end-tidal desflurane and the aepEX and BIS values were calculated by fitting in a nonlinear regression model. RESULTS: The Pk values for the aepEX and the BIS were, respectively, .68 (95% CI, 0.53–0.82) and .85 (95% CI, 0.73–0.96; P = .02). The aepEX and the BIS had an area under the ROC curve of, respectively, 0.89 (95% CI, 0.80–0.95) and 0.76 (95% CI, 0.68–0.84; P = .04). The maximized sensitivity and specificity were, respectively, 81% (95% CI, 61%–93%) and 86% (95% CI, 74%–94%) for the aepEX at a cutoff value of >52, and 69% (95% CI, 56%–81%) and 70% (95% CI, 57%–81%) for the BIS at a cutoff value of >65. The age-corrected end-tidal desflurane concentration associated with an index value of 50 (EC50) was 0.59 minimum alveolar concentration (interquartile range: 0.38–0.85) and 0.58 minimum alveolar concentration (interquartile range: 0.41–0.70) for, respectively, the aepEX and BIS (P = .69). Age-group analysis showed no evidence of a difference regarding the area under the ROC curve or EC50. CONCLUSIONS: The aepEX can reliably differentiate between a conscious and an unconscious state in pediatric patients receiving desflurane-remifentanil anesthesia. Accepted for publication May 8, 2018. Funding: This study was funded by Fonds NutsOhra, Amsterdam, the Netherlands (grant reference number: 1103-060) with an unrestricted project grant and departmental funding. The authors declare no conflicts of interest. Trial registration: https://ift.tt/2tH82DK, NTR2983. Reprints will not be available from the authors. Address correspondence to Yuen M. Cheung, MD, Department of Anesthesiology, Erasmus University Medical Center, Room H-1273, PO Box 2040, 3000 CA Rotterdam, the Netherlands. Address e-mail to y.m.cheung@erasmusmc.nl. © 2018 International Anesthesia Research Society

https://ift.tt/2IDv3Mm

Can STOP-Bang and Pulse Oximetry Detect and Exclude Obstructive Sleep Apnea?

BACKGROUND: Obstructive sleep apnea (OSA) is related to postoperative complications and is a common disorder. Most patients with sleep apnea are, however, undiagnosed, and there is a need for simple screening tools. We aimed to investigate whether STOP-Bang and oxygen desaturation index can identify subjects with OSA. METHODS: In this prospective, observational multicenter trial, 449 adult patients referred to a sleep clinic for evaluation of OSA were investigated with ambulatory polygraphy, including pulse oximetry and the STOP-Bang questionnaire in 4 Swedish centers. The STOP-Bang score is the sum of 8 positive answers to Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index >35 kg/m2, Age >50 years, Neck circumference >40 cm, and male Gender. RESULTS: The optimal STOP-Bang cutoff score was 6 for moderate and severe sleep apnea, defined as apnea-hypopnea index (AHI) ≥15, and the sensitivity and specificity for this score were 63% (95% CI, 0.55–0.70) and 69% (95% CI, 0.64–0.75), respectively. A STOP-Bang score of 15 and a STOP-Bang score of ≥6 had a specificity of 91% (95% CI, 0.87–0.94) for an AHI >15. The items contributing most to the STOP-Bang were the Bang items. There was a positive correlation between AHI versus STOP-Bang and between AHI versus oxygen desaturation index, Spearman ρ 0.50 (95% CI, 0.43–0.58) and 0.96 (95% CI, 0.94–0.97), respectively. CONCLUSIONS: STOP-Bang and pulse oximetry can be used to screen for sleep apnea. A STOP-Bang score of

https://ift.tt/2ICWOEZ

Impact of Regional Anesthesia on Gastroesophageal Cancer Surgery Outcomes: A Systematic Review of the Literature

Regional anesthesia may play a beneficial role in long-term oncological outcomes. Specifically, it has been suggested that it can prolong recurrence-free survival and overall survival after gastrointestinal cancer surgery, including gastric and esophageal cancer, by modulating the immune and inflammatory response. However, the results from human studies are conflicting. The goal of this systematic review was to summarize the evidence on the impact of regional anesthesia on immunomodulation and cancer recurrence after gastric and esophageal surgery. We conducted a literature search of 5 different databases. Two independent reviewers analyzed the quality of the selected manuscripts according to prespecified inclusion and exclusion criteria. Randomized controlled trials were assessed for potential sources of bias by using the Cochrane Risk of Bias tool. A total of 6 studies were included in the quality analysis and systematic review. A meta-analysis was not conducted for several reasons, including high heterogeneity among studies, low quality of the reports, and lack of standardized outcomes definitions. Although the literature suggests that regional anesthesia has some modulatory effects on the inflammatory and immunological response in the studied patient population, our systematic review indicates that there is no evidence to support or refute the use of epidural anesthesia or analgesia with the goal of reducing cancer recurrence after gastroesophageal cancer surgery. Accepted for publication May 23, 2018. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Juan P. Cata, MD, Department of Anaesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Centre, 1515 Holcombe Blvd, Unit 409, Houston, TX 77005. Address e-mail to jcata@mdanderson.org. © 2018 International Anesthesia Research Society

https://ift.tt/2tIaAkO

Observation and Experiment: An Introduction to Causal Inference

No abstract available

https://ift.tt/2N8wSnY

Remifentanil Stability

No abstract available

https://ift.tt/2IFwEkL

Cervical Spine Motion During Tracheal Intubation Using an Optiscope Versus the McGrath Videolaryngoscope in Patients With Simulated Cervical Immobilization: A Prospective Randomized Crossover Study

BACKGROUND: In patients with an unstable cervical spine, maintenance of cervical immobilization during tracheal intubation is important. In McGrath videolaryngoscopic intubation, lifting of the blade to raise the epiglottis is needed to visualize the glottis, but in patients with an unstable cervical spine, this can cause cervical spine movement. By contrast, the Optiscope, a rigid video-stylet, does not require raising of the epiglottis during tracheal intubation. We therefore hypothesized that the Optiscope would produce less cervical spine movement than the McGrath videolaryngoscope during tracheal intubation. The aim of this study was to compare the Optiscope with the McGrath videolaryngoscope with respect to cervical spine motion during intubation in patients with simulated cervical immobilization. METHODS: The primary outcome of the study was the extent of cervical spine motion at the occiput–C1, C1–C2, and C2–C5 segments. In this randomized crossover study, the cervical spine angle was measured before and during tracheal intubation using either the Optiscope or the McGrath videolaryngoscope in 21 patients with simulated cervical immobilization. Cervical spine motion was defined as the change in angle at each cervical segment during tracheal intubation. RESULTS: There was significantly less cervical spine motion at the occiput–C1 segment using the Optiscope rather than the McGrath videolaryngoscope (mean [98.33% CI]: 4.7° [2.4–7.0] vs 10.4° [8.1–12.7]; mean difference [98.33% CI]: −5.7° [−7.5 to −3.9]). There were also fewer cervical spinal motions at the C1–C2 and C2–C5 segments using the Optiscope (mean difference versus the McGrath videolaryngoscope [98.33% CI]: −2.4° [−3.7 to −1.2]) and −3.7° [−5.9 to −1.4], respectively). CONCLUSIONS: The Optiscope produces less cervical spine motion than the McGrath videolaryngoscope during tracheal intubation of patients with simulated cervical immobilization. Accepted for publication May 31, 2018. Funding: None. The authors declare no conflicts of interest. Clinical trial number: ClinicalTrials.gov (NCT03120546). Reprints will not be available from the authors. Address correspondence to Tae Kyong Kim, MD, PhD, Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno, Seoul 03080, Republic of Korea. Address e-mail to ktkktk@gmail.com. © 2018 International Anesthesia Research Society

https://ift.tt/2tHTCmH

Preoperative High-Dose Methylprednisolone and Glycemic Control Early After Total Hip and Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND: To evaluate the effect of a single preoperative dose of 125 mg methylprednisolone (MP) on glycemic homeostasis early after fast-track total hip and knee arthroplasty. METHODS: One-hundred thirty-four patients undergoing elective unilateral total hip arthroplasty and total knee arthroplasty were randomized (1:1) to preoperative intravenous MP 125 mg (group MP) or isotonic saline intravenous (group C). All procedures were performed under spinal anesthesia, using a standardized multimodal analgesic regime. The primary outcome was the change in plasma glucose 2 hours postoperatively, and secondary outcomes included plasma C-peptide concentrations, homeostatic model assessment (HOMA), HOMA-IR (insulin resistance), and HOMA-B (β-cell function). Fasting blood samples were collected at baseline and 2, 6 (nonfasting), 24, and 48 hours after surgery with complete samples from 122 patients (group MP = 62, group C = 60) for analyses. RESULTS: MP patients had increased plasma glucose levels at 2 hours (adjusted mean [95% CI], 7.4 mmol·L−1 [7.2–7.5] vs 6.0 mmol·L−1 [5.9–6.2]; P = .023) and 6 hours (13.9 mmol·L−1 [13.3–14.5] vs 8.4 mmol·L−1 [7.8–9.0]; P

https://ift.tt/2IFwE4f

Novel Application of 32P Brachytherapy: Treatment of Angiolymphoid Hyperplasia with Eosinophilia in the Right Auricle with 8-Year Follow-Up

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


https://ift.tt/2lGYX9k

Neuro-oncology perspective of treatment options in metastatic breast cancer

Future Oncology, Ahead of Print.


https://ift.tt/2KjVBbp

Association of five genetic variations in DNMT1 and DNMT3A with gastric cancer in a Chinese population

Future Oncology, Ahead of Print.


https://ift.tt/2IErUw1

Clinical features and psychological aspects of the decision-making process in stage I testicular germ cell tumors

Future Oncology, Ahead of Print.


https://ift.tt/2KvORX3

Are we doing enough to tackle preventable causes of cancer: an interview with Professor Linda Bauld

Future Oncology, Ahead of Print.


https://ift.tt/2IErO7D

The importance of science communication in cancer research: an interview with Martin Christlieb

Future Oncology, Ahead of Print.


https://ift.tt/2KtTP6z

Cyclophilin A Function in Mammary Epithelium Impacts Jak2/Stat5 Signaling, Morphogenesis, Differentiation, and Tumorigenesis in the Mammary Gland

The prolyl isomerase cyclophilin A (CypA) regulates the Jak2/Stat5 pathway, which is necessary for mammary differentiation and the pathogenesis of breast cancer. In this study, we assessed the role of this isomerase during mammary gland development and erbB2-driven tumorigenesis. Genetic deletion of CypA resulted in delayed mammary gland morphogenesis and differentiation with corresponding decrease in Jak2/Stat5 activation; mammary gland cross-transplantation confirmed this defect was epithelial in nature. Analysis of mammary stem and progenitor populations revealed significant disruption of epithelial maturation. Loss of CypA in the erbB2 transgenic mouse model revealed a marked increase in mammary tumor latency that correlated with decreased Stat5 activation, associated gene expression, and reduced epithelial cell proliferation. These results demonstrate an important role for CypA in the regulation of Jak2/Stat5–mediated biology in mammary epithelium, identifying this isomerase as a novel target for therapeutic intervention.Significance: These findings reveal cyclophilin A functions in normal mammary epithelial development and ErbB2-driven mammary tumorigenesis and suggest therapies targeting cyclophilin A may be efficacious for breast cancer treatment. Cancer Res; 78(14); 1–11. ©2018 AACR. F1

https://ift.tt/2lLo3US

Pathology, Chemoprevention, and Preclinical Models for Target Validation in Barrett Esophagus

Despite esophageal adenocarcinoma (EAC) being the most widespread among gastrointestinal cancers, with an 11-fold increase in the risk of cancer for patients with Barrett esophagus (BE), its prognosis is still poor. There is a critical need to better perceive the biology of cancer progression and identification of specific targets that are the hallmark of BE's progression. This review explores the established animal models of BE, including genetic, surgical and nonsurgical approaches, potential chemoprevention targets, and the reasoning behind their applications to prevent Barrett-related EAC. The key methodological features in the design feasibility of relevant studies are also discussed. Cancer Res; 78(14); 1–8. ©2018 AACR.

https://ift.tt/2yTMkBx

LIFEx: a freeware for radiomic feature calculation in multimodality imaging to accelerate advances in the characterization of tumor heterogeneity

Textural and shape analysis is gaining considerable interest in medical imaging, particularly to identify parameters characterizing tumor heterogeneity and to feed radiomic models. Here we present a free, multiplatform, and easy-to-use freeware called LIFEx, which enables the calculation of conventional, histogram-based textural and shape features from PET, SPECT, MR, CT, and US images, or from any combination of imaging modalities. The application does not require any programming skills and was developed for medical imaging professionals. The goal is that independent and multicenter evidence of the usefulness and limitations of radiomic features for characterization of tumor heterogeneity and subsequent patient management can be gathered. Many options are offered for interactive textural index calculation and for increasing the reproducibility among centers. The software already benefits from a large user community (more than 800 registered users), and interactions within that community are part of the development strategy.

https://ift.tt/2lHIRwj

Mast cells and basophils in allergic inflammation

Masato Kubo

https://ift.tt/2IFjvYX

Cancer-stimulated CAFs enhance monocyte differentiation and pro-tumoral TAM activation via IL-6 and GM-CSF secretion

Purpose: M2-type TAMs are increasingly implicated as a crucial factor promoting metastasis. Numerous cell types dictate monocyte differentiation into M2 TAMs via a complex network of cytokine-based communication. Elucidating critical pathways in this network can provide new targets for inhibiting metastasis. In this study, we focused on cancer cells, CAFs and monocytes as a major node in this network. Experimental Design: Monocyte co-cultures with cancer-stimulated CAFs were used to investigate differentiation into M2-like TAMs. Cytokine array analyses were employed to discover the CAF-derived regulators of differentiation. These regulators were validated in primary CAFs and bone marrow monocytes. Orthotopic, syngeneic colon carcinoma models using co-transplanted CAFs were established to observe effects on tumor growth and metastasis. To confirm a correlation with clinical evidence, meta-analyses were employed using the Oncomine database. Results: Our co-culture studies identify IL-6 and GM-CSF as the pivotal signals released from cancer cell-activated CAFs that co-operate to induce monocyte differentiation into M2-like TAMs. In orthotopic, syngeneic colon carcinoma mouse models, co-transplanted CAFs elevated IL-6 and GM-CSF levels, TAM infiltration and metastasis. These pathological effects were dramatically reversed by joint IL-6 and GM-CSF blockade. A positive correlation between GM-CSF and IL-6 expression and disease course was observed by meta-analyses of the clinical data. Conclusions: Our studies indicate a significant reappraisal of the role of IL-6 and GM-CSF in metastasis and implicate CAFs as the 'henchmen' for cancer cells in producing an immunosuppressive tumor ecological niche. Dual targeting of GM-CSF and IL-6 is a promising new approach for inhibiting metastasis.



https://ift.tt/2IEdZpL

An Anti-CLL-1 Antibody-Drug Conjugate for the Treatment of Acute Myeloid Leukemia

Purpose: The treatment of acute myeloid leukemia (AML) has not significantly changed in 40 years. Cytarabine and anthracycline-based chemotherapy induction regimens (7 + 3) remain the standard of care, and most patients have poor long-term survival. The re-approval of Mylotarg, an anti-CD33-calicheamicin antibody-drug conjugate (ADC), has demonstrated ADCs as a clinically validated option to enhance the effectiveness of induction therapy. We are interested in developing a next generation ADC for AML to improve upon the initial success of Mylotarg. Experimental Design: The expression pattern of CLL-1 and its hematopoietic potential were investigated. A novel anti-CLL-1-ADC, with a highly potent pyrrolobenzodiazepine (PBD) dimer conjugated through a self-immolative disulfide linker, was developed. The efficacy and safety profiles of this ADC were evaluated in mouse xenograft models and in cynomolgus monkeys. Results: We demonstrate that CLL-1 shares similar prevalence and trafficking properties that make CD33 an excellent ADC target for AML, but lacks expression on hematopoietic stem cells that hampers current CD33 targeted ADCs. Our anti-CLL-1-ADC is highly effective at depleting tumor cells in AML xenograft models and lacks target independent toxicities at doses that depleted target monocytes and neutrophils in cynomolgus monkeys. Conclusions: Collectively, our data suggest that an anti-CLL-1-ADC has the potential to become an effective and safer treatment for AML in humans, by reducing and allowing for faster recovery from initial cytopenias than the current generation of ADCs for AML.



https://ift.tt/2KtlzZ4

Functional parameters derived from magnetic resonance imaging reflect vascular morphology in preclinical tumors and in human liver metastases

Purpose: Tumor vessels influence the growth and response of tumors to therapy. Imaging vascular changes in vivo using dynamic contrast-enhanced MRI (DCE-MRI) has shown potential to guide clinical decision making for treatment. However, quantitative MR imaging biomarkers of vascular function have not been widely adopted, partly because their relationship to structural changes in vessels remains unclear. We aimed to elucidate the relationships between vessel function and morphology in vivo. Experimental Design: Untreated preclinical tumors with different levels of vascularization were imaged sequentially using DCE-MRI and computed tomography (CT). Relationships between functional parameters from MR (iAUC, Ktrans, and BATfrac) and structural parameters from CT (vessel volume, radius, and tortuosity) were assessed using linear models. Tumors treated with anti-VEGFR2 antibody were then imaged to determine whether anti-angiogenic therapy altered these relationships. Finally, functional-structural relationships were measured in ten patients with liver metastases from colorectal cancer. Results: Functional parameters iAUC and Ktrans primarily reflected vessel volume in untreated preclinical tumors. The relationships varied spatially and with tumor vascularity, and were altered by anti-angiogenic treatment. In human liver metastases, all three structural parameters were linearly correlated with iAUC and Ktrans. For iAUC, structural parameters also modified each other's effect. Conclusions: Our findings suggest that MR imaging biomarkers of vascular function are linked to structural changes in tumor vessels, and that anti-angiogenic therapy can affect this link. Our work also demonstrates the feasibility of 3D functional-structural validation of MR biomarkers in vivo to improve their biological interpretation and clinical utility.



https://ift.tt/2IEdUlX

Dual Src and MEK inhibition decreases ovarian cancer growth and targets tumor initiating stem-like cells

Purpose: Rational targeted therapies are needed for treatment of ovarian cancers. Signaling kinases, Src and MAPK, are activated in high grade serous ovarian cancer (HGSOC). Here, we tested the frequency of activation of both kinases in HGSOC and the therapeutic potential of dual kinase inhibition. Experimental Design: MEK and Src activation was assayed in primary HGSOC from The Cancer Genome Atlas (TGGA). Effects of dual kinase inhibition were assayed on cell-cycle, apoptosis, gene and proteomic analysis, cancer stem cells and xenografts. Results: Both Src and MAPK are co-activated in 31% of HGSOC, and this associates with worse overall survival on multivariate analysis. Frequent dual kinase activation in HGSOC led us to assay the efficacy of combined Src and MEK inhibition. Treatment of established lines and primary ovarian cancer cultures with Src and MEK inhibitors, saracatinib and selumetinib, respectively, showed target kinase inhibition and synergistic induction of apoptosis and cell cycle arrest in vitro and tumor inhibition in xenografts. Gene expression and proteomic analysis confirmed cell-cycle inhibition and autophagy. Dual therapy also potently inhibited tumor-initiating cells. Src and MAPK were both activated in tumor-initiating populations. Combination treatment followed by drug washout, decreased sphere formation and ALDH1+cells. In vivo, tumors dissociated after dual therapy showed a marked decrease in ALDH1 staining, sphere formation and loss of tumor-initiating cells upon serial xenografting. Conclusions: Selumetinib added to saracatinib overcomes EGFR/HER2/ERBB2-mediated bypass activation of MEK/MAPK observed with saracatinib alone and targets tumor-initiating OVCA populations, supporting further evaluation of combined Src-MEK inhibition in clinical trials.



https://ift.tt/2Kx9LVK

Skeletal Muscle Loss is an Imaging Biomarker of Outcome After Definitive Chemoradiotherapy for Locally Advanced Cervical Cancer

Purpose: This study investigates the association between body composition change during concurrent chemoradiotherapy (CCRT) and outcome in patients with locally advanced cervical cancer (LACC). Experimental Design: Pre- and post-treatment computed tomography (CT) images of 245 patients with LACC who were treated between 2004 and 2015 were analysed. Skeletal muscle index (SMI) and density (SMD), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured from two sets of CT images at the level of the L3 vertebra. Sarcopenia and a low SMD were defined using published cut-points. Predictors of overall survival (OS) and cancer-specific survival (CSS) were analysed using Cox regression models. Results: The median follow-up was 62.7 (range, 7.3-152.3) months. Among the 245 patients, 127 (51.8%) had pre-treatment sarcopenia and 154 (62.9%) had a low SMD. SMI did not decrease significantly during CCRT, 0.6%/150 days (95% CI: -1.8 to 0.6; p = 0.35). However, a SMI loss during CCRT of >10.0%/150 days was independently associated with poorer OS (hazard ratio: 6.02, 95% confidence interval: 3.04-11.93; p < 0.001) and CSS (hazard ratio: 3.49, 95% confidence interval: 1.44-8.42; p = 0.006) when adjusted for FIGO stage, pathology, and treatment. Pre-treatment sarcopenia and change of SMD, SATI, and VATI during CCRT were not associated with survival. Conclusions: Skeletal muscle measurements could be imaging biomarkers to predict outcomes for patients with LACC in clinical practice. Further studies are needed to determine whether multimodal interventions can preserve skeletal muscle mass and thereby improve survival.



https://ift.tt/2IBHUyP

Prehabilitation May Improve Post Cardiac Surgery Outcomes

FRIDAY, June 29, 2018 -- A three-pronged approach to prehabilitation, which includes improving nutritional status, exercise capacity, and worry reduction, may improve outcomes after cardiac surgery, according to a study published online June 27 in...

https://ift.tt/2MBjB6u

Nitric Oxide Cuts Kidney Injury After Long Cardiac Surgery

FRIDAY, June 29, 2018 -- Nitric oxide gas may lead to a reduction in the incidence of acute kidney injury and an improvement in long-term kidney function in patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass,...

https://ift.tt/2KkHRgw

Most Pediatricians in the United States Do Not Support Spanking

FRIDAY, June 29, 2018 -- Most pediatricians in the United States do not support spanking children and are aware of evidence that spanking increases the risk of poor health outcomes in children, according to a study published in the Journal of...

https://ift.tt/2MCrWXF

Practice Management Can Improve Efficiency

FRIDAY, June 29, 2018 -- Providers can take practical steps to improve practice efficiency and increase insurance reimbursement, according to an article published in Dermatology Times. In a talk at the American Academy of Dermatology annual meeting...

https://ift.tt/2KvJvLs

Direct Primary Care Can Be Beneficial to Patients

FRIDAY, June 29, 2018 -- Conversion to direct primary care (DPC)/retainer-based/concierge care models does not necessarily result in patient abandonment, but rather in improved patient care, according to a blog post published June 18 in Medical...

https://ift.tt/2MBoDjn

GrapHi-C: graph-based visualization of Hi-C datasets

Hi-C is a proximity-based ligation reaction used to detect regions of the genome that are close in 3D space (or "interacting"). Typically, results from Hi-C experiments (contact maps) are visualized as heatmap...

https://ift.tt/2yUIVCb

Avoiding Catch-22: validating the PainDETECT in a in a population of patients with chronic pain

Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system and is a major therapeutic challenge. Several screening tools have been developed to help physicians detect...

https://ift.tt/2KvzRIK

NExT: Advancing Promising Cancer Therapies from the Lab to Clinical Trials

The NCI Experimental Therapeutics (NExT) program works with researchers and top scientific experts to advance promising or novel cancer therapies from the earliest stages of research to human clinical trials.



https://ift.tt/2tRfviz

The organization of Danish emergency departments

Introduction Twenty-one new Danish emergency departments (EDs) were established following a 2007 policy reform that included ED autonomy to self-organize. The aim of this study was to describe the organization of the 21 departments and their organizational challenges. Participants and methods We used a qualitative design based on COREQ guidelines. All 21 EDs participated, and 123 semi-structured interviews with hospital and ED leaders, physicians, nurses, and secretaries were performed between 2013 and 2015. We used the framework matrix method to investigate the ED goals, setting, structure, staff, task coordination, and incentive structure. Results We identified three generic models (virtual, hybrid, and independent). All had goals of high quality of care and high efficiency. The virtual model was staffed by junior physicians and tasks were coordinated by other departments. The hybrid model was staffed by junior physicians and senior physicians according to other departments and the ED. The ED coordinated all activities. The independent model was staffed by junior physicians and senior physicians, and activities were coordinated by the ED. Of the EDs, 19 utilized different organizational models at different times during a 24-h period and on weekdays and weekends. The main challenge of the virtual and hybrid models was high dependency on other departments. The main challenge of the independent model was establishing a high level of quality of emergency medicine. Discussion and conclusion We identified three organizational ED models (virtual, hybrid, and independent). Nineteen EDs used more than one organizational model depending on the time of day or day of the week. Correspondence to Anders Moellekaer, MD, MBA, Research Center for Emergency Medicine, Aarhus University Hospital, Noerrebrogade 44, Bygning 30, 1. sal, DK-8000 Aarhus, Denmark Tel: +45 20 848 304; e-mail: anders.moellekaer@ki.au.dk Received January 7, 2017 Accepted April 13, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2IEluNf

Next-Generation Sequencing May Improve Pediatric Epilepsy Tx

FRIDAY, June 29, 2018 -- Next-generation sequencing (NGS) can improve treatment efficacy and reduce hospitalization in children with drug-resistant epilepsy (DRE), according to a study published online June 22 in CNS Neuroscience &...

https://ift.tt/2z1kbZ0

Weight Loss Linked to Reversal of Atrial Fibrillation Progression

FRIDAY, June 29, 2018 -- For obese patients offered weight and risk factor management (RFM), weight loss is associated with reversal of the type and progression of atrial fibrillation (AF), according to a study published online June 14 in...

https://ift.tt/2lJxLXR

The American Diabetes Association, June 22-26

The American Diabetes Association's 78th Scientific Sessions The annual meeting of the American Diabetes Association (ADA) was held from June 22 to 26 in Orlando, Florida, and attracted approximately 14,000 participants from around the world,...

https://ift.tt/2z1EFkK

New Technique Allows Rapid Bedside Measurement of GFR

FRIDAY, June 29, 2018 -- A visible fluorescent injectate (VFI)-based approach for direct measurement of glomerular filtration rate (mGFR) is accurate with high reproducibility, according to a study published in the June issue of the Journal of the...

https://ift.tt/2tPxRAM

Twitter Posts Reveal Use of JUUL Vaporizer by Minors at School

FRIDAY, June 29, 2018 -- Data from social media capture early public experiences with the JUUL vaporizer, a nicotine delivery device that is the size and shape of a thumb drive, according to a study published in the June 26 issue of Drug and Alcohol...

https://ift.tt/2lJxKmL

Decision Tree Model Can ID Behaviors Linked to Sunburn Risk

FRIDAY, June 29, 2018 -- A decision tree analytic technique shows the interactive effects of sun protective behaviors on the likelihood of sunburn, according to a study published online June 27 in JAMA Dermatology. Kasey L. Morris, Ph.D., and Frank...

https://ift.tt/2lJxILF

Initial Outcomes No Worse for Surgical ICU Patients With CA

FRIDAY, June 29, 2018 -- Surgical patients who are admitted to the intensive care unit (ICU) and have cancer do not have worse initial outcomes than those without cancer, according to a study published online June 27 in JAMA Surgery. Kathryn Puxty,...

https://ift.tt/2yV71wV

AMA Calls for Electronic Health Record Training

FRIDAY, June 29, 2018 -- The American Medical Association (AMA) is calling on medical schools and residency programs to incorporate electronic health record (EHR) training into their curricula. According to the AMA, the new policy aims to address...

https://ift.tt/2lLmvtU

Prolonged Leisure-Time Sitting Tied to Increased Mortality Risk

FRIDAY, June 29, 2018 -- Prolonged leisure-time sitting is associated with increased risk of mortality, according to a study published online in the American Journal of Epidemiology. Alpa V. Patel, Ph.D., from the American Cancer Society in Atlanta,...

https://ift.tt/2tPkQXJ

High-throughput DNA Extraction and Genotyping of 3dpf Zebrafish Larvae by Fin Clipping

58024fig1.jpg

Zebrafish have been used as reliable genetic model organisms in biomedical research, especially with the advent of gene-editing technologies. When larval phenotypes are expected, DNA extraction and genotype identification can be challenging. Here, we describe an efficient genotyping procedure for zebrafish larvae, by tail clipping, as early as 72-h post-fertilization.

https://ift.tt/2lGX9NN

Pancreatic Islet Embedding for Paraffin Sections

Ex vivo pancreatic islet studies are important for diabetes research. Existing techniques to study cultured islets in their native 3-dimensional architecture are time consuming, inefficient, and infrequently used. This work describes a new, simple, and efficient method for generating high-quality paraffin sections of whole cultured islets.

https://ift.tt/2yVNgVZ

The Replica Set Method: A High-throughput Approach to Quantitatively Measure Caenorhabditis elegans Lifespan

Here we describe the Replica Set method, an approach to quantitatively measure C. elegans lifespan/survival and healthspan in a high-throughput and robust manner, thus allowing screening of many conditions without sacrificing data quality. This protocol details the strategy and provides a software tool for analysis of Replica Set data.

https://ift.tt/2N5rUbL

Optogenetic Entrainment of Hippocampal Theta Oscillations in Behaving Mice

We describe the use of optogenetics and electrophysiological recordings for selective manipulations of hippocampal theta oscillations (5-10 Hz) in behaving mice. The efficacy of the rhythm entrainment is monitored using local field potential. A combination of opto- and pharmacogenetic inhibition addresses the efferent readout of hippocampal synchronization.

https://ift.tt/2ICAxHc

Prevention of Nosocomial Infections in Critically Ill Patients With Lactoferrin: A Randomized, Double-Blind, Placebo-Controlled Study

Objective: To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study. Design: Phase 2, multicenter, randomized, double-blind, placebo-controlled study. Setting: Medical-surgical ICUs. Patients: Adult, critically ill patients receiving invasive mechanical ventilation. Interventions: Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days. Measurements and Main Results: Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [SD], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; p = 0.91) and nosocomial infections (0.3 [0.7] vs 0.4 [0.6] per patient; p = 0.48) did not differ between lactoferrin and placebo groups, respectively. Clinical outcomes for lactoferrin versus placebo were as follows: ICU length of stay (14.5 [18.0] vs 15.0 [37.3] d; p = 0.82), hospital length of stay (25.0 [25.9] vs 28.1 [44.6] d; p = 0.57), hospital mortality (41.1% vs 30.5%; p = 0.11), and 90-day mortality (44.9% vs 32.4%; p = 0.06). Biomarker levels did not differ between the groups. Conclusions: Lactoferrin did not improve the primary outcome of antibiotic-free days, nor any of the secondary outcomes. Our data do not support the conduct of a larger phase 3 trial. The study was conceptualized by Dr. Muscedere. All authors contributed to the conduct of the study and/or provided input on the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by grants from the Lotte and John Hecht Memorial Foundation and South Eastern Academic Medical Association. The bovine lactoferrin was provided by Advanced Orthomolecular Research. The funders did not have any role in the conceptualization, conduct of the study, study analysis, interpretation of the data, or writing of the article. Dr. Muscedere, Dr. Maslove, Dr. Boyd, Ms. O'Callaghan, Dr. Reynolds, Dr. Hall, and Dr. Jones disclosed off-label product use of lactoferrin for the reduction of nosocomial infections. Dr. Boyd's institution received funding from South Eastern Academic Medical Association (SEAMO) Innovation Fund and SEAMO New Clinician Scientist Award, and he received funding from Physician Services Incorporated New Clinician Science Award. Dr. Hall's institution received funding from Queen's University, Canadian Institutes for Health Research, and GlaxoSmithKline. Mr. Day's institution received funding from Queen's University Faculty of Health Sciences to Kingston General Hospital Research Institute. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: muscedej@kgh.kari.net Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2KAln7n

A Case for Change in Adult Critical Care Training for Physicians in the United States: A White Paper Developed by the Critical Care as a Specialty Task Force of the Society of Critical Care Medicine

Objectives: In the United States, physician training in Critical Care Medicine has developed as a subspecialty of different primary boards, despite significant commonality in knowledge and skills. The Society of Critical Care Medicine appointed a multidisciplinary Task Force to examine alternative approaches for future training. Design: The Task Force reviewed the literature and conducted informal discussions with key stakeholders. Specific topics reviewed included the history of critical care training, commonalities among subspecialties, developments since a similar review in 2004, international experience, quality patient care, and financial and workforce issues. Main Results: The Task Force believes that options for future training include establishment of a 1) primary specialty of critical care; 2) unified fellowship and certification process; or 3) unified certification process with separate fellowship programs within the current specialties versus 4) maintaining multiple specialty-based fellowship programs and certification processes. Conclusions: 1) Changing the current Critical Care Medicine training paradigms may benefit trainees and patient care. 2) Multiple pathways into critical care training for all interested trainees are desirable for meeting future intensivist workforce demands. 3) The current subspecialties within separate boards are not "distinct and well-defined field[s] of medical practice" per the American Board of Medical Specialties. Recommendations for first steps are as follows: 1) as the society representing multidisciplinary critical care, the Society of Critical Care Medicine has an opportunity to organize a meeting of all stakeholders to discuss the issues regarding Critical Care Medicine training and consider cooperative approaches for the future. 2) A common Critical Care Medicine examination, possibly with a small percentage of base-specialty–specific questions, should be considered. 3) Institutions with multiple Critical Care Medicine fellowship programs should consider developing joint, multidisciplinary training curricula. 4) The boards that offer Critical Care Medicine examinations, along with national critical care societies, should consider ways to shorten training time. Drs. Tisherman and Spevetz are Co-Chair persons. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Supported, in part, by the Society of Critical Care Medicine. Dr. Tisherman has disclosed that he represents the Society of Critical Care Medicine (SCCM) on the Trauma, Burns, and Critical Care Board of the American Board of Surgery, and he is also President of the Surgical Critical Care Program Directors Society. Dr. Spevetz has disclosed that she serves as the SCCM representative to the American Board of Internal Medicine (ABIM) Liaison committee on Certification and Recertification. Dr. Brown serves as an examiner for the American Board of Anesthesiology. Dr. Chang received funding from SCCM (Council Member; financial relationship related only to reimbursement for travel expenses and complimentary registration for the annual congress; no honoraria), the Neurocritical Care Society (Past-President; nonvoting, ex-officio member of the Board of Directors; financial relationship limited to travel expenses to stand-alone Board meetings; no honoraria), ABIM Critical Care Medicine Certification Examination Writing Committee (current member, travel expenses and honorarium), and received reimbursement for travel and honoraria for lectures at annual meetings from the American College of Physicians, and from the Indonesian SCCM for a Multiprofessional Critical Care Review Course for Continuing Education Program for their membership. She also disclosed that she was the Co-Chair (Past/Inaugural Chair) for the Neurocritical Care Examination Writing Committee of the United Council of Neurological Subspecialties and the Certification Committee for the Neurocritical Care Society. Dr. O'Connor received funding from CLEW (previously known as Intensix; scientific advisory board). Dr. Sevransky's institution received funding from the Marcus Foundation, and he received funding from SCCM (Associate Editor stipend). He is an associate editor of Critical Care Medicine. Dr. Wessman is the Program Director for the Anesthesiology Critical Care Medicine Fellowship at Washington University of St. Louis and the Chair of the SCCM Emergency Medicine Section. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: stisherman@umm.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2Kiw8iy

Compliance With the National SEP-1 Quality Measure and Association With Sepsis Outcomes: A Multicenter Retrospective Cohort Study

Objectives: Many septic patients receive care that fails the Centers for Medicare and Medicaid Services' SEP-1 measure, but it is unclear whether this reflects meaningful lapses in care, differences in clinical characteristics, or excessive rigidity of the "all-or-nothing" measure. We compared outcomes in cases that passed versus failed SEP-1 during the first 2 years after the measure was implemented. Design: Retrospective cohort study. Setting: Seven U.S. hospitals. Patients: Adult patients included in SEP-1 reporting between October 2015 and September 2017. Interventions: None. Measurements and Main Results: Of 851 sepsis cases in the cohort, 281 (33%) passed SEP-1 and 570 (67%) failed. SEP-1 failures had higher rates of septic shock (20% vs 9%; p

https://ift.tt/2Klf5MI

Specific and Accurate Detection of the Citrus Greening Pathogen Candidatus liberibacter spp. Using Conventional PCR on Citrus Leaf Tissue Samples

Citrus Greening is a particularly destructive disease affecting citrus crops globally. Presented here is a simple method using PCR and genomic DNA extraction of citrus leaf tissue for the accurate and precise identification of the citrus greening pathogen, Candidatus liberibacter spp.

https://ift.tt/2MBsc9k

Testing Animal Anxiety in Rats: Effects of Open Arm Ledges and Closed Arm Wall Transparency in Elevated Plus Maze Test

Rats' anxiety-like behavior tested by the elevated plus maze varies highly depending on the testing environment. Here we show how apparatus settings, especially arm structure, affect behavior on the maze, and we explain a reliable protocol to detect effects of anxiolytic drugs. This report will contribute to anxiety research.

https://ift.tt/2KjjAYa

Multiple HBV transfusion transmissions from undetected occult infections: revising the minimal infectious dose

Objective

HBV infection by blood components is currently prevented in most developed countries by combining sensitive HBV surface antigen (HBsAg) assays, nucleic acid testing (NAT) and in a few of them antibodies against the HBV core antigen (anti-HBc) screening. HBV transmissions by blood components from three repeat donors tested negative for HBsAg and HBV DNA with a highly sensitive screening test (limit of detection (LOD): 3.4 IU/mL) were investigated.

Design

30 of the 47 recipients of components produced from these three donors were examined. Transfusion transmission was confirmed by phylogenetic analysis of viral sequences obtained from recipients and donors following viral particle concentration.

Results

9 of 31 (29%) recipients were infected: 7 infections were related to 200 mL of fresh frozen plasma and 2 infections to red blood cells containing 20 mL plasma. Transfusion transmission was confirmed by >99% identity of donor/recipient sequences in five cases, probable in three and possible in one. HBV active infection remained unsuspected for 24–57 months in three recipients. Five non-infected recipients carried anti-HBs when transfused. Six patients transfused with platelet concentrates treated with a pathogen reduction method were not infected. These data enabled to revise previous estimate of the minimal infectious dose from approximately 100 to 16 copies (or 3 IU) of HBV DNA.

Conclusions

HBV transfusion transmission from occult HBV infection carrying extremely low viral loads is related to plasma volume transfused and possibly prevented by anti-HBs. HBV blood safety could be further improved by either anti-HBc screening, HBV DNA NAT with a LOD of 0.8 copies/mL (0.15 IU/mL) or pathogen reduction of blood components.



https://ift.tt/2Kl8nGw

What is required from HCV point-of-care tests to reduce the burden of hepatitis C infection? 'Development and clinical validation of the genedrive point-of-care test for qualitative detection of hepatitis C virus

The major advances in hepatitis C virus (HCV) diagnosis and treatment now make hepatitis C infection a curable disease over a short period of time and thus, theoretically, an eliminable disease. In its viral hepatitis elimination plan, the WHO aims, by 2030, to scale-up HCV treatment coverage to 80% and reduce HCV incidence and related mortality by 90% and 65%, respectively.1 This plan is ambitious and requires new strategies for the identification of hepatitis C cases especially in resource-limited countries which bear the highest burden of disease. The WHO estimates that only 20% of the 71 million individuals infected with HCV globally have been diagnosed and <10% have been treated.2 These figures are even lower in resource-limited countries. This poor intervention coverage is not only related to limited access to direct antiviral agents at low cost but also to the high cost and complexity of the conventional...



https://ift.tt/2KuroCf

Prognostic significance of high serum p53 antibody titers in patients with esophageal squamous cell carcinoma

Abstract

Background

The p53 protein overexpression that usually results from genetic alterations reportedly induces serum antibodies against p53. However, little information is available about the prognostic significance of perioperative serum p53 antibody (s-p53-Abs) titers in patients with esophageal squamous cell carcinoma.

Methods

In this study, we retrospectively evaluated the clinical significance of perioperative s-p53-Abs in 135 patients with esophageal squamous cell carcinoma. Of these, 58 patients received neoadjuvant chemotherapy comprising 5-FU and CDDP. While the cutoff level at 1.3 U/ml indicated seropositive patients, level of 13.4 U/ml was used to identify high-titer patients. We monitored serum titers seropositive patients after surgery and evaluated the prognostic significance by the univariate and multivariate analyses.

Results

In this study, 29 patients (21.5%) were positive for s-p53-Abs before treatment. The frequency of both seropositive patients and high-titer patients (> 13.4 U/ml) was not significantly associated with tumor progression. While seropositive patients did not demonstrate significant poor overall survival, high-titer patients demonstrated significant poor overall survival based on the multivariate analysis (P < 0.001). Moreover, the s-p53-Abs titer did not correlate with the response to neoadjuvant chemotherapy. Among seropositive patients, the negative conversion of s-p53-Abs more likely led to be long-term survival.

Conclusions

This study determined that the high-titer of s-p53-Abs was an independent risk factor to reduce the overall survival of patients with esophageal cancer patients. The negative conversion of s-p53-Abs could be a good indicator of favorable prognosis.



https://ift.tt/2KBG8Q4

Radiotherapy combined with zoledronate can reduce skeletal-related events in renal cell carcinoma patients with bone metastasis

Abstract

Background

Skeletal-related events (SRE) are common in patients with renal cell carcinoma (RCC) that includes bone metastasis. The purpose of this study was to clarify the effectiveness of zoledronate with and without sunitinib, combined with radiotherapy, for the treatment of bone metastasis from RCC.

Methods

We retrospectively analyzed 62 RCC patients with bone metastasis, who had been treated with radiotherapy at our institution. We divided the study cohort into two groups: patients treated with radiotherapy alone (RT; n = 27) and those treated with radiotherapy combined with zoledronate (RT + Z; n = 35). We investigated the overall survival and post-irradiation (PI)-SRE-free rate for each group, as well as the effect of sunitinib in the RT + Z treatment group. In addition, we determined treatment effectiveness by imaging assessments and relative response rates.

Results

There was no significant difference in the survival rates between the RT and RT + Z treatment groups (p = 0.11). However, the PI-SRE-free rate in the RT + Z group was significantly higher than that in the RT group (p = 0.02). The PI-SRE-free rate was significantly higher in patients who were treated with sunitinib after radiotherapy than in those who were treated without sunitinib (p = 0.03). However, there was no significant difference in the relative response rates, as assessed by imaging, in each group.

Conclusion

Radiotherapy combined with zoledronate is an effective treatment for RCC with bone metastasis to prevent PI-SRE. Sunitinib may reduce PI-SRE if used after radiotherapy and combined with zoledronate.



https://ift.tt/2Kw8ACM

Enzymes That Catalyze Wobble tRNA Modification Promote Melanomagenesis [Research Watch]

Enzymes that modify wobble uridine 34 tRNAs (U34 enzymes) maintain HIF1α levels in BRAFV600E melanoma.



https://ift.tt/2N7dDey

Transcription Factor Low-Complexity Domain Hubs Drive Transcription [Research Watch]

Low-complexity domains (LCD) in transcription factors can form high-concentration interaction hubs.



https://ift.tt/2yVreme

The Histone Demethylase LSD1 Inhibits Tumor Cell Immunogenicity [Research Watch]

Loss of LSD1 enhances tumor immunogenicity and sensitizes refractory mouse melanoma to anti–PD-1 therapy.



https://ift.tt/2N98jaB

Phase Separation Concentrates Transcription Proteins at Superenhancers [Research Watch]

Intrinsically disordered regions of MED1 and BRD4 promote formation of phase-separated condensates.



https://ift.tt/2yTX8PX

IFN-β Improves Sepsis-related Alveolar Macrophage Dysfunction and Postseptic Acute Respiratory Distress Syndrome–related Mortality

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 1, Page 45-55, July 2018.


https://ift.tt/2KsmDMX

TRPV4 Stimulation Releases ATP via Pannexin Channels in Human Pulmonary Fibroblasts

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 1, Page 87-95, July 2018.


https://ift.tt/2KwRYea

Platelets: Pivotal Player in Primary Sensitization to Allergen?

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 1, Page 7-8, July 2018.


https://ift.tt/2Ky6Jka

July Highlights/Papers by Junior Investigators/NIH News

American Journal of Respiratory Cell and Molecular Biology, Volume 59, Issue 1, Page i-i, July 2018.


https://ift.tt/2Mteghe

Salubrinal Enhances Doxorubicin Sensitivity in Human Cholangiocarcinoma Cells Through Promoting DNA Damage

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


https://ift.tt/2Ky6C8e

Early Hospital Readmissions after an Acute Exacerbation of Chronic Obstructive Pulmonary Disease in the Nationwide Readmissions Database

Annals of the American Thoracic Society, Volume 15, Issue 7, Page 837-845, July 2018.


https://ift.tt/2N59eJb

Computerized Cognitive Rehabilitation in Intensive Care Unit Survivors: Returning to Everyday Tasks Using Rehabilitation Networks–Computerized Cognitive Rehabilitation Pilot Investigation

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Annals of the American Thoracic Society, Volume 15, Issue 7, Page 887-891, July 2018.


https://ift.tt/2KvYEcs

Epidemiology of Clonal Pseudomonas aeruginosa Infection in a Canadian Cystic Fibrosis Population

Annals of the American Thoracic Society, Volume 15, Issue 7, Page 827-836, July 2018.


https://ift.tt/2N8VnkY

The Cost of Caring: Emotion, Burnout, and Psychological Distress in Critical Care Clinicians

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Annals of the American Thoracic Society, Volume 15, Issue 7, Page 787-790, July 2018.


https://ift.tt/2IDFcbX

Bilateral Lung Masses and Dyspnea in a Young Woman

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Annals of the American Thoracic Society, Volume 15, Issue 7, Page 875-879, July 2018.


https://ift.tt/2NbaACf

Boosting Clinical Decision-making: Machine Learning for Intensive Care Unit Discharge

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Annals of the American Thoracic Society, Volume 15, Issue 7, Page 804-805, July 2018.


https://ift.tt/2KznZ58

Predicting Intensive Care Unit Readmission with Machine Learning Using Electronic Health Record Data

Annals of the American Thoracic Society, Volume 15, Issue 7, Page 846-853, July 2018.


https://ift.tt/2N9RJHG

Access to Supplemental Oxygen Therapy: A Crisis

Annals of the American Thoracic Society, Volume 15, Issue 7, Page 893-894, July 2018.


https://ift.tt/2KwP1KC

Is It Time to Move on from Identifying Risk Factors for 30-Day Chronic Obstructive Pulmonary Disease Readmission? A Call for Risk Prediction Tools

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Annals of the American Thoracic Society, Volume 15, Issue 7, Page 801-803, July 2018.


https://ift.tt/2tI5FAo

Unclassifiable Interstitial Lung Disease: Time to Shrink the Black Box

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Annals of the American Thoracic Society, Volume 15, Issue 7, Page 806-807, July 2018.


https://ift.tt/2ICm8uw

Epidemiology of Pulmonary Nontuberculous Mycobacterial Sputum Positivity in Patients with Cystic Fibrosis in the United States, 2010–2014

Annals of the American Thoracic Society, Volume 15, Issue 7, Page 817-826, July 2018.


https://ift.tt/2tGCaPt

Heterogeneity in Unclassifiable Interstitial Lung Disease. A Systematic Review and Meta-Analysis

Annals of the American Thoracic Society, Volume 15, Issue 7, Page 854-863, July 2018.


https://ift.tt/2IClVYg

Erratum: International Practice Variation in Weaning Critically Ill Adults from Invasive Mechanical Ventilation

Annals of the American Thoracic Society, Volume 15, Issue 7, Page 894-894, July 2018.


https://ift.tt/2N9RnAQ

Endobronchial Ultrasound for Nodal Staging of Patients with Non–Small-Cell Lung Cancer with Radiologically Normal Mediastinum. A Meta-Analysis

Annals of the American Thoracic Society, Volume 15, Issue 7, Page 864-874, July 2018.


https://ift.tt/2KwOhoO

Realizing the Paris Climate Agreement to Improve Cardiopulmonary Health. Where Science Meets Policy

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Annals of the American Thoracic Society, Volume 15, Issue 7, Page 791-798, July 2018.


https://ift.tt/2tGBTvV

Duration of Home Oxygen Therapy in Young Children Enrolled in an Accountable Care Organization

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Annals of the American Thoracic Society, Volume 15, Issue 7, Page 891-893, July 2018.


https://ift.tt/2KwxOAW

Successful Deployment of Two Balloon-Expandable Stents Using an In-Stent Bifurcating Approach

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Annals of the American Thoracic Society, Volume 15, Issue 7, Page 884-886, July 2018.


https://ift.tt/2N7rP7f

Chronic Obstructive Pulmonary Disease Education in Pulmonary Rehabilitation. An Official American Thoracic Society/Thoracic Society of Australia and New Zealand/Canadian Thoracic Society/British Thoracic Society Workshop Report

Annals of the American Thoracic Society, Volume 15, Issue 7, Page 769-784, July 2018.


https://ift.tt/2ICcS9V

Reply: Access to Supplemental Oxygen Therapy: A Crisis

Annals of the American Thoracic Society, Volume 15, Issue 7, Page 894-894, July 2018.


https://ift.tt/2NbnCzI

Rare Cause of Respiratory Failure: A Twist in the Tale

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Annals of the American Thoracic Society, Volume 15, Issue 7, Page 880-883, July 2018.


https://ift.tt/2ICcJ6n

Americans Exaggerate Their Home State’s Role in Building the Nation

As the United States celebrates its founding on July 4, research on "collective narcissism" suggests many Americans have hugely exaggerated notions about how much their home states helped to write the nation's narrative.

"Our study shows a massive narcissistic bias in the way that people from the United States remember the contributions of their home states to U.S. history," said Henry L. "Roddy" Roediger, professor of psychological and brain sciences in Arts & Sciences at Washington University in St. Louis and senior author of the study.

The study, published in Psychological Science, a journal of the Association for Psychological Science, is based on a national survey of nearly 4,000 U.S. residents, including about 50-60 respondents from each of the nation's 50 states.

Asked to estimate their home state's contribution to U.S. history, participants routinely gave their home state higher scores than those provided by non-residents of the state.

"As we originally hypothesized, the original 13 colonies, Texas, and California showed high levels of narcissism, but there were also some surprises," said Adam Putnam, the study's first author and assistant professor of psychology at Furman University in South Carolina. "For example, people from Kansas and Wyoming thought much more of their state than nonresidents."

Map 1

Residents' ratings of their state's contributions to U.S. history. Darker colors and higher percentages represent a larger estimated contribution. (Source: Psychological Science)

Collective narcissism — a phenomenon in which individuals show excessively high regard for their own group — has been studied extensively in smaller social circles, such as workplaces and communities. Psychologists have explored the idea that people over-claim responsibility for shared tasks for a long time, but this study is among the first to research its effects among huge virtual groups of loosely connected individuals scattered across entire states.

While it is difficult for anyone to accurately estimate an individual state's contribution to the nation's history, it is mathematically reasonable to expect the sum total of individual state contributions to add up to a figure in the vicinity of 100 percent.

Instead, the average percentage contributions estimated by residents of each state in this study added up to a staggering 907 percent, more than nine times higher than logic suggests.

Roediger grew up in Virginia and was not surprised that his home state was on the high end of the continuum, claiming responsibility for 41 percent of the nation's history.

"We would study U.S. history one year, then Virginia history the next. Many of the events are the same: Jamestown, the Revolution, four of the first five presidents being from Virginia, all the Civil War battles," he recalls.

When people in other states were asked about Virginia's percentage contribution to U.S. history, they also gave a high number: 24 percent.

In an effort to see if state narcissism could be reduced by exposure to the realities of U.S. history, researchers divided the sample into two groups, requiring half to take a quiz designed to remind them of the true breadth of U.S. history before they answered the relevant question. The other half answered the question first, before they took the quiz. However, placement of the question about how much the person's state contributed did not matter. The average across the 50 states was 18.1 percent whether the question was posed first or was placed last.

"The responses are even more amazing because we explicitly tell people in the question that there are 50 states and the total contribution of all states should equal 100 percent — even with that reminder Americans give really high responses," Putnam said. "Being reminded about the scope of U.S. history before making the estimate doesn't seem to lower the responses."

Putnam, who earned a doctorate in psychology from Washington University in 2015, has worked with Roediger on other studies of collective narcissism, including a just-published paper that applies the same methodology to 35 nations around the globe.

That study, which found that residents of Malaysia considered themselves responsible for 39 percent of world history, has important implications for how residents of these countries view one another and interact on the world stage.

Roediger and Putnam offer several explanations for the skewed perceptions uncovered in the study of collective narcissism among residents of American states.

For starters, people know a lot more about their home state than other states: they study state history in school, visit museums, and so on. All of this information comes to mind quickly and easily compared to information about other states (a phenomenon known as the availability heuristic).

A second factor is that social psychology research has clearly shown that people like to associate with successful groups and think of themselves as being slightly above-average on a variety of positive traits.

Finally, people might not be particularly good at making quantitative estimates about small numbers.

"The most important take away from this research is that people may appear to be egocentric or narcissistic about their own groups, but there isn't necessarily anything malicious or evil about it — it is just the way we view the world," Putnam said. "There is certainly concern about tribalism in today's culture, so this project is a nice reminder to try and think about how people from different backgrounds see things."



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