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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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

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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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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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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

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

Apparent Hyperthyroidism Caused by Biotin-Like Interference from IgM Anti-Streptavidin Antibodies

Thyroid, Ahead of Print.


https://ift.tt/2lKRypO

Sobetirome and its Amide Prodrug Sob-AM2 Exert Thyromimetic Actions in Mct8-Deficient Brain

Thyroid, Ahead of Print.


https://ift.tt/2tSicQW

Protective Effect of Metformin Against Thyroid Cancer Development: A Population-Based Study in Korea

Thyroid, Ahead of Print.


https://ift.tt/2lKRzdm

American Thyroid Association Statement on Postoperative Hypoparathyroidism: Diagnosis, Prevention, and Management in Adults

Thyroid, Ahead of Print.


https://ift.tt/2lGWwDI

Retraction of: Hair Iodine for Human Iodine Status Assessment, Thyroid 24(6);2014:1018–1026; DOI: 10.1089/thy.2012.0499

Thyroid, Ahead of Print.


https://ift.tt/2tSU3tC

Structure of a Thyrotropin Receptor Monoclonal Antibody Variable Region Provides Insight into Potential Mechanisms for its Inverse Agonist Activity

Thyroid, Ahead of Print.


https://ift.tt/2lIo77G

Mast cells and basophils in allergic inflammation

Masato Kubo

https://ift.tt/2IFjvYX

Mechanisms leading to T-cell activation in drug hypersensitivity

Purpose of review Delayed-type or nonimmediate drug hypersensitivity reactions often involve the activation of drug-specific T cells. As such, the molecular initiating event is an interaction between HLA proteins, HLA-binding peptides and the drug. For many years, the formation of covalently modified drug protein adducts was assumed to be a prerequisite for T-cell activation. The purpose of this article is to review recent studies using human PBMC, T-cell lines and clones, which show that drugs are in fact loaded onto HLA molecules in different forms to activate T cells. Recent findings We now know that protein-reactive drugs such as β-lactam antibiotics activate T cells via direct noncovalent interactions with HLA or HLA-binding peptides, direct covalent modification of HLA-binding peptides and covalent binding of non-HLA associated proteins. Adducts formed inside and outside of the cells undergo protein processing to generate HLA-binding peptides that are assumed to contain the drug modification. Studies using synthetic stable (e.g. oxypurinol) and reactive (e.g. nitroso sulfamethoxazole) metabolites show that metabolites activate T cells via the same pathways. A variety of drugs with different structural features have also been shown to activate T cells though a direct HLA-binding interaction. Of note, abacavir behaves in an unexpected way, binding deep in the peptide binding cleft of one HLA, selectively activating CD8+ T cells. Summary In-vitro studies have revealed that a number of drug HLA-binding interactions lead to the activation of T cells. These can be categorized according to two hypotheses, namely hapten and pharmacological interactions. As we move forward with the development of diagnostic and predictive T-cell assays, it is critical to reach a consensus that direct drug HLA binding and the formation of drug protein adducts are important events for T-cell activation.

https://ift.tt/2N8qjBP

Does evidence support the use of cat allergen immunotherapy?

Purpose of review Cat allergy can manifest as allergic rhinitis, conjunctivitis and/or asthma. With widespread cat ownership and exposure, cat allergy has emerged as a major cause of morbidity. Cat allergen immunotherapy is a potential disease modifying treatment for patients with cat allergy. We examine evidence on the effectiveness, cost-effectiveness and safety of cat allergen immunotherapy and consider the clinical contexts in which it should be prescribed. Recent findings The European Association of Allergy and Clinical Immunology systematic reviews on allergic rhinitis and asthma along with the accompanying guidelines on allergic rhinitis were used as primary sources of evidence. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are most common routes of administration for allergen immunotherapy (AIT). A limited number of high-quality studies related to cat dander have shown mixed results in improvements in ocular and nasal symptoms, asthma symptoms, peak expiratory flow rate and medication use scores with subcutaneous immunotherapy. Two studies examining cat dander and cat-related allergy response with sublingual immunotherapy have shown mixed results in terms of symptomatic response. One randomized trial examining intralymphatic immunotherapy has shown a positive symptom response and a favourable safety profile. Although studies have reported mixed results regarding safety of SCIT, adverse events have been reported more commonly with SCIT than SLIT. Summary There is a limited body of high-quality evidence on the effectiveness and safety of cat AIT and no high-quality data on its cost-effectiveness. The available evidence on effectiveness is mixed based on studying a limited array of immunological, physiological and patient-reported outcome measures. Based on this evidence and extrapolating on the wider evidence base in AIT, it is likely that some patients may benefit from this modality of treatment, particularly those with moderate-to-severe disease who are inadequately controlled on allergen avoidance measures and pharmacotherapy and those who are monosensitized to Felix Domesticus 1. Further evidence is, however, required from larger trials before more definitive advice can be offered.

https://ift.tt/2IHOrYQ

Advances in hypersensitivity drug reactions

No abstract available

https://ift.tt/2NcykGb

Management of adverse reactions to first-line tuberculosis antibiotics

Purpose of review Tuberculosis (TB) is the commonest infectious cause of death globally. Adverse reactions to first-line tuberculosis antibiotics are common and have a major impact on the outcomes of patients as second-line antibiotics are less effective and more toxic. The present review addresses the most recent literature regarding epidemiology, investigating reactions, and reintroducing treatment in patients who have had their treatment interrupted. Recent findings Studies have demonstrated that up to 60% of patients experience adverse reactions to TB treatment; around a third of these are idiosyncratic and may relate to immune sensitization. There is an increased risk in patients with HIV. For patients with severe cutaneous reactions patch testing has an important role; however, systemic reactions to patch testing are common in patients with HIV. In-vitro testing remains limited to specialist centers but studies have identified drug-specific lymphocyte responses in patients with cutaneous and liver reactions. Desensitization of patients with severe cutaneous reactions have been demonstrated to be possible, albeit at high risk. Summary Management of these patients remains suboptimal. Better identification of predisposing factors, such as HLA alleles, are needed to identify patients at risk. Improved in-vitro diagnostics will reduce the need to re-expose the patient to the drug and optimized desensitization regimens will improve patient safety when drugs have to be re-introduced.

https://ift.tt/2IA444p

Hypersensitivity reactions to beta-lactams in children

Purpose of review To present the most recent evidence on beta-lactam hypersensitivity reactions in children. Recent findings Drug provocation tests (DPTs) are the gold standard when investigating beta-lactam allergy in children and evidence is increasingly supporting DPTs without skin tests as a safe approach when evaluating children with nonimmediate mild reactions to beta-lactams. Of note, data are limited in the adolescent population, and this attitude may not apply to this age group. Standardization of DPT protocols is required in nonimmediate reactions, as many protocols ranging from 1 to 10 days have been described. The optimal duration of DPT is still unknown, with extended protocols providing slightly more sensitivity and possible higher long-term compliance, at the expense of potential side effects associated with prolonged antibiotic use. On the other hand, 1-day DPTs will identify the vast majority of patients, and the rest will only develop a mild rash during a subsequent full treatment. The natural history of beta-lactam allergy in children is not well studied with recent evidence pointing to the resolution of most confirmed beta-lactam allergies after 3 years. Summary Further studies are needed for the standardization of DPT protocols and to confirm the favourable natural history of beta-lactam drug allergies in children. In addition, multicentric studies are required to confirm the increasingly accepted position of performing DPTs without skin tests in nonimmediate mild reactions to beta-lactams and to further evaluate the possibility of performing DPTs in benign immediate reactions to beta-lactams in children.

https://ift.tt/2tGNhYQ

Editorial introductions

No abstract available

https://ift.tt/2IEmbWH

NSAIDs hypersensitivity: questions not resolved

Purpose of review NSAIDs are the drugs most frequently involved in hypersensitivity reactions (HSR). These are frequently prescribed at all ages. HSR are of great concern and can affect people at any age. These drugs can induce reactions by stimulating the adaptive immune system (IgE or T cell), known as selective responders or more frequently by abnormalities in biochemical pathways related with prostaglandin metabolism. These are known as cross-intolerant. With some exceptions, skin testing and in-vitro studies are of little value in selective responders. Recent findings In the last years, several classifications have been provided based on clinical symptoms, time interval between drug intake and appearance of symptoms, response to other nonchemically related NSAIDs and the underlying disease. Based on this classification, several well differentiated categories within each group of entities cross-intolerant and selective responders are now recognized. The most complex groups for evaluation are cross-intolerant in which three major groups exist: NSAIDs exacerbated respiratory disease, NSAIDs exacerbated cutaneous disease and NSAIDs-induced urticaria/angioedema in the absence of chronic spontaneous urticaria. Within the selective responders, there are two mechanisms involved: drug-specific IgE or T-cell effector responses. New entities have been added to this classification like mixed reactions within the cross-intolerant category, that must manifest as anaphylaxis and multiple immediate selective reactions. Summary The precise evaluation of patients with NSAIDs hypersensitivity following established guidelines will improve not only our understanding but also the management of these entities. As the number of patients affected with NSAIDs is important, further studies are warranted.

https://ift.tt/2N8q7m5

Genetic and nongenetic factors that may predispose individuals to allergic drug reactions

Purpose of review Defining predisposition to allergic drug reactions has largely focussed on HLA associations, but other genetic and nongenetic factors are also likely to be involved. Recent findings Polymorphic genetic variants in cytokine genes, including IL-10, and co-signalling pathways, including CTLA4, have been associated with allergic drug reactions, but the effect size is lower than with HLA alleles and most associations have not been replicated. Although TCR specificity seems to be important for CBZ-induced SJS/TEN in South East Asian patients, a distinct repertoire may not play a role in reactions to other drugs. New mass spectrometric techniques allowing for the identification of naturally eluted peptides from drug-exposed HLA alleles will allow for the antigenic source of T-cell activation to be defined and may shed light on the influence of disease. Indeed, preliminary data highlight the propensity of drug-responsive T cells to cross-react with T cells primed to viral antigens. Furthermore, the environment can epigenetically influence regulatory gene expression, suggesting that an individual's family exposure history may alter immune thresholds and tip the balance toward activation. Summary It is likely that predisposition to allergic drug reactions is multifaceted in most cases. This will require the study of large numbers of patients to detect genetic factors that have a lower effect size than HLA alleles. This should be accompanied by detailed clinical phenotyping of patients and the assessment of the immunological phenotype with respect to the presence and type of drug antigen-responsive T cells.

https://ift.tt/2KycHy7

The potential role of pharmacogenomics and biotransformation in hypersensitivity reactions to paracetamol

Purpose of review The aim of the present review is to discuss recent advances supporting a role of paracetamol metabolism in hypersensitivity reactions to this drug. Recent findings Recent developments in the identification of novel paracetamol metabolites, as well as in allele frequencies and functional effects of genetic variation leading to the bioavailablity of reactive paracetamol metabolites, have led to the identification of potential pharmacogenomic and metabolomic targets in studies seeking mechanisms involved in hypersensitivity reactions caused by this drug. Particularly relevant are identification of araquidonate metabolites, identification of specific-binding sequences for reactive paracetamol metabolite-protein adducts, and studies on the frequencies and the functional impact of duplication or multiduplication of genes involved in the formation of reactive metabolites, as well as complete gene deletion or deleterious mutations in genes involved in the detoxification of paracetamol reactive metabolites. In addition, recent evidence points to sex, ethnic origin and age as relevant factors in the production of reactive paracetamol metabolites. Summary High inter-individual variability in the production of reactive paracetamol metabolites exists, and factors leading to increased bioavailability of reactive paracetamol metabolites are being uncovered. Additional research is required to link these factors to paracetamol-induced hypersensitivity reactions.

https://ift.tt/2N8q1ed

Is the evidence of local allergic rhinitis growing?

Purpose of review To examine the recent advances on epidemiological studies, diagnostic approach and clinical management of local allergic rhinitis (LAR) in adults and children. Recent findings Evidence about LAR is growing especially in pediatric and Asian populations. The prevalence of LAR is lower in Asian countries compared with western countries in both children and adults. LAR is considered a chronic condition and an independent rhinitis phenotype that affects up to 26.5% of nonatopic rhinitis patients. The disease rapidly progress toward the clinical worsening with associated onset of asthma and conjunctivitis, which further impairs patient's quality of life. Nasal Allergen Provocation Test is the diagnostic gold standard that can be complemented by basophil activation test and the detection of specific IgE in nasal secretions. Allergen immunotherapy induces a significant and early improvement in both clinical symptoms and quality of life in LAR patients. Summary LAR is a common entity, with different prevalence depending on geographical locations. LAR has to be considered in the process of differential diagnosis in children and adults with rhinitis. Diagnosis of LAR is crucial in order to start an etiologic treatment such as allergen immunotherapy, which has proven to be very effective in these patients.

https://ift.tt/2IBA6gv

Interaction between foods and nonsteroidal anti-inflammatory drugs and exercise in the induction of anaphylaxis

Purpose of review To assess the studies that focus on the study of food-dependent exercise-induced anaphylaxis (FDEIA) and food-dependent NSAID-induced anaphylaxis (FDNIA). Recent findings Cofactors, as exercise and nonsteroidal anti-inflammatory drugs (NSAIDs), are relevant in up to 30% of episodes of anaphylaxis. Gliadin and lipid transfer proteins are the main allergens involved. The attempts to reproduce FDEIA and FDNIA in a controlled setting have an important failure rate. The cyclooxigenase (COX) pathway could play an important role in the underlying mechanisms: NSAIDs and exercise increase the permeability of the intestinal barrier. This effect is stronger with NSAID that inhibit both isoforms than with preferential COX-2 inhibitor. Basophils obtained from FDNIA patients, showed an increase of its activation with the food allergen with lysine–aspirin compared with the food allergen alone. This potentiating effect was not observed when basophils were stimulated with the food allergen with selective COX-2 inhibitor. Other mechanisms including transient receptor potential superamily, reactive oxygen species, altered B-cell pathway and increased neutrophil activation markers have been speculated. Summary The frequent implication of cofactors, as exercise and NSAID, in food-induced anaphylaxis highlights the importance of recognizing and including them into diagnostic workup. The understanding of the underlying mechanisms would help in the development of diagnostic and therapeutic strategies.

https://ift.tt/2tGpp7L

Monoclonal antibodies for the treatment of atopic dermatitis

Purpose of review To evaluate the treatment revolution atopic dermatitis, the most common inflammatory skin disease, has been going through in recent years, thanks to breakthroughs in disease understanding, delineating the immune fingerprint of atopic dermatitis. Recent findings The treatment for moderate-to-severe atopic dermatitis patients has been largely unchanged for decades and relied on broad-acting immunosuppressants. A huge unmet need existed for effective, well tolerated and narrow-targeted therapeutics. Multiple therapies, targeting various aspects of the complex immune activation of atopic dermatitis, are now assessed in clinical trials, and hold promise for a new era in the treatment of atopic dermatitis, comparable with the treatment shift seen for psoriasis in the last decade. The first effective monoclonal antibody licensed for the treatment of atopic dermatitis, dupilumab, not only offers a much-needed systemic agent for moderate-to-severe patients but also provides strong evidence for the potential role of other monoclonal antibodies in disease management. Summary In this rapidly changing field, new atopic dermatitis-targeted monoclonal antibodies will be reviewed in light of the recently discovered pathomechanisms of the disease.

https://ift.tt/2IEqgKG

Tension band plating of an anterior tibial stress fracture nonunion in an elite athlete, initially treated with intramedullary nailing: a case report

Leg pain in athletes is a common condition and is often related to tibial stress fracture. When non-operative treatment fails, the optimal surgical treatment is controversial. The aim of this study was to repo...

https://ift.tt/2lHfFWd

EMA Panel Backs Combo Drug for Hyperuricemia in Gout Patients

Duzallo contains two medicines in one pill to address both the underelimination and overproduction of uric acid. The FDA approved the drug in August 2017.
International Approvals

https://ift.tt/2tDxHNG

Evaluation of lung function in patients submitted to total laryngectomy

Publication date: Available online 29 June 2018
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Mario A. Castro, Rogério A. Dedivitis, João M. Salge, Leandro L. Matos, Claudio R. Cernea
IntroductionThe post-laryngectomy state presents with several alterations in lung function. A reliable estimation of lung function can be very useful in laryngectomees to prevent postoperative complications and to evaluate the results of the treatment.ObjectiveCharacterize the presence of respiratory functional disorders and the functional pattern of laryngectomees through the use of an extratracheal device.MethodsThis transversal study included 50 patients who had undergone total laryngectomy at least 6 months prior to this investigation, as the treatment of choice for laryngeal cancer.Results56% percent of the participants had altered breathing pattern, distributed as follows: 14 with obstructive pattern with no air trapping, 11 with obstructive pattern with air trapping and only 3 with restrictive pattern. On average, the diffusion decreased (74.3%) and airway resistance increased (121.7%) when compared to the expected average values for the Brazilian individuals.ConclusionMost patients submitted to total laryngectomy present altered lung function, usually the obstructive type, frequently associated to a history of smoking.



https://ift.tt/2KCnHxX

FDA OKs New Topical Treatment for Excessive Underarm Sweating

Qbrexza (Dermira) is a topical anticholinergic cloth applied to the underarms and is designed to block sweat production by inhibiting sweat gland activation in patients with axially primary hyperhidrosis.
FDA Approvals

https://ift.tt/2lK7VTv

Atopic dermatitis in Chinese patients shows TH2/TH17-skewing with psoriasiform features

Publication date: Available online 28 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Tom C. Chan, Riana D. Sanyal, Ana B. Pavel, Jacob Glickman, Xiuzhong Zheng, Hui Xu, Yung-Tsu Cho, Tsen-Feng Tsai, Huei-Chi Wen, Xiangyu Peng, Inna Cueto, James G. Krueger, Emma Guttman-Yassky

Teaser

Our data established the molecular fingerprints of AD and psoriasis in Han Chinese patients, and identified tissue biomarkers of disease that correlated with clinical severity.


https://ift.tt/2KydoYr

Alternaria is associated with asthma symptoms and exhaled NO among NYC children

Publication date: Available online 28 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Nitzan Soffer, Brett J. Green, Luis Acosta, Adnan Divjan, Edward Sobek, Angela R. Lemons, Andrew G. Rundle, Judith S. Jacobson, Inge F. Goldstein, Rachel L. Miller, Matthew S. Perzanowsk

Teaser

Among NYC children, Alternaria sensitization, even at low IgE concentrations, was associated with asthma morbidity. Domestic Alternaria exposure, which was common, was associated with exhaled NO, specifically among children with higher neighborhood-level combustion air pollution.


https://ift.tt/2Kv6UN4

The Role of Selective Balloon Occlusion in Preoperative Planning for Infant Pulmonary Lobar Hyperinflation

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.


https://ift.tt/2lI4H2T

The Johns Hopkins Hospital Achieves Magnet Recognition Again

Baltimore (June 29, 2018) — The Johns Hopkins Hospital has once again achieved Magnet designation in recognition of its nursing excellence. The American Nurses Credentialing Center's Magnet Recognition Program is the highest national credential for professionalnursing practice. Only about 7.5 percent of U.S. health care organizations have achieved Magnet recognition.

https://ift.tt/2MxwMFi

Neoadjuvant BRAF- and Immune-Directed Therapy for Anaplastic Thyroid Carcinoma

Thyroid, Ahead of Print.


https://ift.tt/2lGsYpT

Potential of traditionally consumed medicinal herbs, spices, and food plants to inhibit key digestive enzymes geared towards diabetes mellitus management — A systematic review

Publication date: Available online 29 June 2018
Source:South African Journal of Botany
Author(s): A.D. Seetaloo, M.Z. Aumeeruddy, R.R. Rengasamy Kannan, M.F. Mahomoodally
Diabetes mellitus is a notorious endocrine disorder with a high global prevalence. Currently available drugs to manage such noncommunicable disease and related complications are associated with various adverse effects and discomforts. It has been argued that the use of herbs and spices can inhibit key carbohydrate and lipid digestive enzymes (amylase, glucosidase, and lipase), thereby regulating blood glucose levels and postprandial peaks in diabetics. Indeed, before the expansion of conventional medicine, dietary measures and food plants were the mainstay therapies to manage panoply of diseases, including diabetes. Nonetheless, there is still a dearth of comprehensive compilation of the potential of traditionally used herbs and spices to inhibit key digestive enzymes. This study aimed to bring to the limelight of the scientific community a comprehensive updated systematic review of the potential of traditionally used herbs, spices, and food plants which have been used traditionally against diabetes. Using the PRISMA methodology, a comprehensive and structured literature search was conducted in key databases (Pubmed, ScienceDirect, and Google Scholar). Published literature was scrutinised using specific keywords and only those published from 2008 to 2017 were included in this review. A total of 94 plants were identified as having digestive enzyme inhibitory properties; five of them against all three enzymes, 41 for both amylase and glucosidase, and one against both amylase and lipase. Different families of plants, plant parts, and type of extracts have been found to exhibit different strengths of enzyme inhibitory activities. Several research gaps have been identified that warrants due attention in future studies. It is anticipated that this study will open new avenues for research and advocates the need to probe traditional and indigenous herbs and food plants in the management of diabetes.



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Prevalence of Abnormal Postures in Parkinson's Disease

Condition:   Parkinson Disease
Intervention:  
Sponsor:   Universita di Verona
Recruiting

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A Study to Evaluate the Safety and Efficacy of Lenvatinib in Participants With Refractory Differentiated Thyroid Cancer

Condition:   Thyroid Neoplasms
Intervention:   Drug: Lenvatinib
Sponsor:   Eisai Inc.
Recruiting

https://ift.tt/2KvMKCr

Pembrolizumab After Lung SBRT for Medically Inoperable Early Stage Non-small Cell Lung Cancer

Condition:   Non Small Cell Lung Cancer
Interventions:   Drug: Pembrolizumab;   Radiation: Stereotactic body radiotherapy
Sponsor:   Case Comprehensive Cancer Center
Not yet recruiting

https://ift.tt/2IDTut1

Tuberculous arthritis: negative Xpert MTB/RIF assay does not rule out infection!

We present a case of a 31-year-old man of Indian origin with no previous medical history who presented with an inflamed knee. Treatment for bacterial infection was unsuccessful, and needle aspiration of the left knee effusion/collection was smear and culture positive for tuberculosis (TB), despite Xpert MTB/RIF being falsely negative. The patient was commenced on quadruple therapy for TB and within 2 months had improved significantly with no clinical evidence of ongoing inflammation.

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Indoleamine 2,3-dioxygenase provides adaptive resistance to immune checkpoint inhibitors in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Immune checkpoint blockade with anti-CTLA-4 and anti-PD-1 antibodies has shown promising results in the treatment of patients with advanced HCC. The anti-PD-1 antibody, nivolumab, is now approved for patients who have had progressive disease on the current standard of care. However, a subset of patients with advanced HCC treated with immune checkpoint inhibitors failed to respond to therapy. Here, we provide evidence of adaptive resistance to immune checkpoint inhibitors through upregulation of indoleamine 2,3-dioxygenase (IDO) in HCC. Anti-CTLA-4 treatment promoted an induction of IDO1 in resistant HCC tumors but not in tumors sensitive to immune checkpoint blockade. Using both subcutaneous and hepatic orthotopic models, we found that the addition of an IDO inhibitor increases the efficacy of treatment in HCC resistant tumors with high IDO induction. Furthermore, in vivo neutralizing studies demonstrated that the IDO induction by immune checkpoint blockade was dependent on IFN-γ. Similar findings were observed with anti-PD-1 therapy. These results provide evidence that IDO may play a role in adaptive resistance to immune checkpoint inhibitors in patients with HCC. Therefore, inhibiting IDO in combination with immune checkpoint inhibitors may add therapeutic benefit in tumors which overexpress IDO and should be considered for clinical evaluation in HCC.

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Remodeling of the Corneal Epithelial Scaffold for Treatment of Persistent Epithelial Defects in Diabetic Keratopathy

Background: To develop a strategy based on surgical removal of a degenerated corneal epithelial scaffold for treatment of persistent epithelial defects (PEDs) in diabetic keratopathy. Case Presentation: Three diabetic patients with PEDs were initially treated with eyedrops containing the fibronectin-based peptide PHSRN (Pro-His-Ser-Arg-Asn) or both the substance P-derived peptide FGLM-NH₂ and the insulin-like growth factor-1-derived peptide SSSR. A degenerated Bowman's layer or calcified lesion thought to be responsible for incomplete healing was surgically removed after confirmation of reactivity to the peptide eyedrops. All three patients achieved complete epithelial wound closure after surgery. Two cases treated by phototherapeutic keratectomy or lamellar keratoplasty did not show PED recurrence during 6 or 36 months of follow-up, respectively. One case treated by mechanical removal of a degenerated Bowman's layer manifested recurrence after 1 month, but resurfacing of the defect was again achieved after repeat surgery. Conclusion: We propose a new strategy for treatment of diabetic PEDs based on surgical remodeling of the corneal epithelial scaffold for patients who respond to peptide eyedrops but fail to achieve wound closure.
Case Rep Ophthalmol 2018;9:333–340

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The effects of recombinant human epidermal growth factor containing ointment on wound healing and post inflammatory hyperpigmentation prevention after fractional ablative skin resurfacing: A split‐face randomized controlled study

Journal of Cosmetic Dermatology, EarlyView.


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Comprehensive review of the extended middle cranial fossa approach

Purpose of review To review the current literature on the extended middle cranial fossa (xMCF) approach and to provide a comprehensive description of the relevant anatomy, indications, surgical technique, results, and complications. Recent findings The xMCF approach expands the surgical exposure provided by the sMCF approach, allowing access to the internal auditory canal, cerebellopontine angle, prepontine cistern, anterior petrous apex, petrous carotid artery, Meckel's cave, cavernous sinus, mid and upper clivus, and posterior lesions approaching the jugular foramen. Preservation of serviceable hearing is possible with success rates approximating 50% in vestibular schwannoma and meningioma resection, and facial nerve outcome is excellent. Summary The xMCF is an important approach for difficult to access lesions that additionally offers the possibility of hearing preservation. This approach is also useful for vascular lesions, auditory brainstem implantation, and lesions of mid-brainstem. Correspondence to Ravi N. Samy, MD, FACS, Chief, Division of Otology/Neurotology, Program Director, Neurotology Fellowship, Department of Otolaryngology – Head and Neck Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Neurosensory Disorders Center, University of Cincinnati Neuroscience Institute, 213 Albert Sabin Way, MSB 6407, Cincinnati, OH 45267-0528, USA. Tel: +1 513 558 1273; fax: +1 513 558 5203; e-mail: Ravi.Samy@UC.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Single-cell epigenetics – Chromatin modification atlas unveiled by mass cytometry

Publication date: Available online 28 June 2018
Source:Clinical Immunology
Author(s): Peggie Cheung, Francesco Vallania, Mai Dvorak, Sarah E. Chang, Steven Schaffert, Michele Donato, Aditya Rao, Rong Mao, Paul J. Utz, Purvesh Khatri, Alex J. Kuo
Modifications of histone proteins are fundamental to the regulation of epigenetic phenotypes. Dysregulations of histone modifications have been linked to the pathogenesis of diverse human diseases. However, identifying differential histone modifications in patients with immune-mediated diseases has been challenging, in part due to the lack of a powerful analytic platform to study histone modifications in the complex human immune system. We recently developed a highly multiplexed platform, Epigenetic landscape profiling using cytometry by Time-Of-Flight (EpiTOF), to analyze the global levels of a broad array of histone modifications in single cells using mass cytometry. In this review, we summarize the development of EpiTOF and discuss its potential applications in biomedical research. We anticipate that this platform will provide new insights into the roles of epigenetic regulation in hematopoiesis, immune cell functions and immune system aging, and reveal aberrant epigenetic patterns associated with immune-mediated diseases.



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