Source:Annals of Allergy, Asthma & Immunology
Author(s): Aude Belbézier, Isabelle Boccon-Gibod, Aurélie Du Thanh, Olivier Fain, Laurence Bouillet
https://ift.tt/2tJeGJD
Agenesis of the dorsal pancreas is very rare. Less than 70 cases have been reported to date. Some of these cases had an association with a tumor. The literature of agenesis of the dorsal pancreas and agenesis ...
https://ift.tt/2IDGrbe
Publication date: Available online 30 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Sarita U. Patil, Wayne G. Shreffler
The development and widespread use of vaccines, which are defined by the World Health Organization as "biological preparations that improve immunity to a particular disease," represents one of the most significant strides in medicine. Vaccination was first applied to reduce mortality and morbidity from infectious diseases. The World Health Organization estimates that vaccines prevent 2 to 3 million human deaths annually, and these numbers would increase by at least 6 million if all children received the recommended vaccination schedule. However, the origins of allergen immunotherapy share the same intellectual paradigm, and subsequent innovations in vaccine technology have been applied beyond the prevention of infection, including in the treatment of cancer and allergic diseases. This review will focus on how new and more rational approaches to vaccine development use novel biotechnology, target new mechanisms, and shape the immune system response, with an emphasis on discoveries that have direct translational relevance to the treatment of allergic diseases.
https://ift.tt/2lH5Ck6
Publication date: September 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 112
Author(s): Qi-Yuan Zou, Yang Shen, Xia Ke, Su-Ling Hong, Hou-Yong Kang
ObjectivesAllergic rhinitis (AR), a common chronic inflammatory disease in the upper airways. The prevalence of AR in children seems to be increasing recently, and the most significant causes of the increase are thought to be changes in environmental factors, especially air pollution. However, we could not find any meta-analysis on the risk of air pollution exposure on the prevalence of AR in childhood. The aim of this research was to carry out a meta-analysis on the results of recent studies (21 s t century) to present valid information about exposure to air pollution and risk of prevalence of childhood AR.MethodsPubMed, Science, Google Scholar, Elsevier and MDPI web database were searched up to January 1, 2000 to February 28, 2018. Including of air pollution and AR in childhood related to the observation of literature. Meta-analysis, study quality assessment, heterogeneity analysis and publication bias test were using Stata-MP 14.1 and Review Manager version 5.3 software.Results13 studies will be included in the meta-analysis (8 cross-sectional studies, 5 cohort studies). Exposure to NO2 (OREurope = 1.031, 95%CI [1.002,1.060], P = 0.033; ORAsia = 1.236, 95%CI [1.099,1.390], P = 0.000; ORoverall = 1.138, 95%CI [1.052,1.231], P = 0.001); Exposure to SO2 (OREurope = 1.148, 95%CI [1.030,1.279], P = 0.012; ORAsia = 1.044, 95%CI [0.954,1.142], P = 0.352; ORoverall = 1.085, 95%CI [1.013,1.163], P = 0.020); Exposure to PM10 (OREurope = 1.190, 95%CI [1.092,1.297], P = 0.000; ORAsia = 1.075, 95%CI [0.995,1.161], P = 0.066; ORoverall = 1.125, 95%CI [1.062,1.191], P = 0.000); Exposure to PM2.5 (OREurope = 1.195, 95%CI [1.050,1.360], P = 0.007; ORAsia = 1.163, 95%CI [1.074,1.260], P = 0.000; ORoverall = 1.172, 95%CI [1.095,1.254], P = 0.000).ConclusionsExposed to air pollution probable is a risk of prevalence of childhood AR. And the prevalence of AR will be increase when exposed to NO2, SO2, PM10 and PM2.5, but maybe the relationship between SO2/PM10 and prevalence of AR are not closely in Asia.
https://ift.tt/2tEvnWK
Publication date: September 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 112
Author(s): Tyler R. Schwartz, Miranda D. Colletta, Michael E. McCormick
The disease of parapharyngeal abscess is well known to the otolaryngologist and is commonly managed via transoral, transcervical, or combined incision and drainage. We report a novel approach to an abscess that was drained through the external auditory canal (EAC). An otherwise healthy 2-year-old female presented with a 4-day history of fevers, decreased oral intake, neck stiffness, and voice changes. CT neck with contrast revealed a deep abscess in the left neck extending from the peritonsillar space into the parapharyngeal space in close proximity to the anterior aspect of the EAC. Because the EAC was the closest surface to the abscess collection, we elected to attempt drainage through this route. Successful incision and drainage was performed via transcanal approach. She received intravenous antibiotics and steroids post-operatively and surgical packing was removed. She was discharged home on post-operative day 5 afebrile and tolerating a regular diet and continued to do well at most recent outpatient follow-up.
https://ift.tt/2NeygFw
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.
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.
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.
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.
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...
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.
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...
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.
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.
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.
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...
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.
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.
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.
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.
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.
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...
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...
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...
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.
QuestionWhat is the diagnosis (see figure 1)?
(A) Pulmonary artery...
Thyroid, Ahead of Print.
https://ift.tt/2lKRypO
Thyroid, Ahead of Print.
https://ift.tt/2tSicQW
Thyroid, Ahead of Print.
https://ift.tt/2lKRzdm
Thyroid, Ahead of Print.
https://ift.tt/2lGWwDI
Thyroid, Ahead of Print.
https://ift.tt/2tSU3tC
Thyroid, Ahead of Print.
https://ift.tt/2lIo77G
Masato Kubo
https://ift.tt/2IFjvYX
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
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
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
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
Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.
https://ift.tt/2lI4H2T
Thyroid, Ahead of Print.
https://ift.tt/2lGsYpT
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.
https://ift.tt/2tR0tcL
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.
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.
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2IBrJkR
Publication date: Available online 28 June 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Stephen J. Galli
https://ift.tt/2yVstBY