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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 22 Μαΐου 2017
Global surgery: current evidence for improving surgical care.
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Relationship between various anthropometric measures and apnea-hypopnea index in Korean men
Body mass index (BMI) has been shown to be strongly correlated with severity of OSA. However, BMI has not been shown to be correlated with sleep apnea in all patients studied. The purpose of this study was to evaluate the relationship between various anthropometric measures and severity of OSA according to BMI in men.
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Scalp and Forehead Defects in the Post-Mohs Surgery Patient
Scalp and forehead reconstruction after Mohs micrographic surgery can encompass subcentimeter defects to entire scalp reconstruction. Knowledge of anatomy, flap design, and execution will prepare surgeons who operate in the head and neck area to confidently approach a variety of reconstructive challenges in this area.
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Necrotic cutaneous vasculitic skin lesions: a case of atypical Henoch-Schönlein purpura in a child with heterozygosity for factor V Leiden
Description
A Caucasian boy aged 5 years presented with acute onset of a non-tender, palpable purpuric rash to his lower limbs, preceded by a mild upper respiratory tract infection. Clinical findings were consistent with Henoch-Schönlein purpura (HSP) and he was discharged with community follow-up to monitor his lesions, blood pressure and urinalysis.
However, he clinically deteriorated over the following week with two further admissions due to evolving purpuric skin lesions (figure 1) and development of severe joint pain requiring opioid analgesia. There was no clinical evidence of renal or intestinal involvement.
Figure 1
Initial presentation of the purpuric Henoch Schonlein purpura rash.
Over a subsequent 6-week period, his purpuric lesions progressed to full thickness skin necrosis (figure 2). This was confirmed by a plastic surgery assessment and he was referred for a tertiary rheumatology review. He underwent a series...
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Surgery in late melanoma adrenal metastasis
Metastatic melanoma to adrenal gland are very infrequent, being generally associated with additional evidence of systemic disease and, consequently, with short-term survival. However, the prognosis and the therapeutic management vary depending on some important oncological features. Long-term survival rates have been described after complete resection of metastatic disease. Here, we report the case of a woman aged 41 years diagnosed with a cutaneous melanoma on the right side of her paravertebral region, level III of Clark, in 2002, who underwent surgical excision of the tumour with negative margins and a negative sentinel node. She posteriorly developed pulmonary metastasis in 2006 and 2009, both resected with curative intention and in 2013, she was diagnosed with an adrenal metastasis. Therefore, she was submitted to an uneventful right laparoscopic adrenalectomy. The pathology report described metastasis of a cutaneous melanoma, negative for BRAF mutation. The patient is actually disease-free after 30 months of follow-up.
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Unusual course of a haematoma of the thigh
Description
A Caucasian woman aged 56 years presented to emergency room (ER) department with leucorrhoea and fever since 48 hours. She was a smoker, had no diabetes history, no prosthetic material and denied use of injected drugs.
A month before, the patient had a closed inguinal trauma due to fall from height with a muscle strain of the anterior right thigh. Despite rest and analgesics, she went to ER several times because of progressive local pain and swelling. After 3 weeks, a local ultrasound scan showed a 3 cm size haematoma associated with probable rupture of obturator internus and rectus femoris muscles. On the following days, she developed fetid leucorrhoea associated with movements and compression of the anterior thigh. On physical examination and analyses, she had sepsis criteria and the abdomen/pelvic CT scan (figure1A, B) and MRI (figure1C, D) showed an abscess of 105x25mm size, complicated with...
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Bottom of an iceberg: undiagnosed aortic aneurysm masquerading as vocal cord palsy
Description
A previously healthy woman aged 60 years was referred to a tertiary referral cancer centre with change of voice for 1 week suspecting neoplastic aetiology on account of her tobacco chewing habit of more than 20 years. No history of voice abuse, fever or cough was there preceding the onset of the change of voice. She did not have any previous history of hospitalisation or diagnosed comorbidities. On clinical examination, her pulse rate was 82 bpm; blood pressure was 130/90 mm Hg and respiratory rate was 12/min.
Video laryngoscopy examination revealed left vocal cord palsy with no obvious lesion. A whole-body F18 FDG PET–CT scan revealed the presence of 6.6x4.8x6.7 cm lobulated sacullar aneurysm arising from the aortic arch between the origins of the left common carotid and subclavian arteries (figures 1 and 2). The likely mycotic aneurysm caused significant surrounding metabolically active inflammatory changes (figure 3). The...
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Effect of follicular dendritic cell secreted protein on gene expression of human periodontal ligament cells
Source:Archives of Oral Biology, Volume 81
Author(s): Lin Xiang, Na Xin, Ying Yuan, Xiaogang Hou, Junwei Chen, Na Wei, Ping Gong
ObjectiveThe objective of this study was to investigate the specific roles of follicular dendritic cell secreted protein (FDC-SP), a protein exists in saliva, in the inhibition of calcium precipitation during periodontal regeneration, as well as affect phenotype expression of human periodontal ligament cells (hPDLCs) during the differentiation process.DesignTo investigate this, we applied microarray technology to identify gene expression changes in hPDLCs transfected with FDC-SP and then clustered them according to their biological functions.ResultsOne hundred seventy-one genes were found differentially expressed by at least two-fold between FDC-SP -transfected and empty vector-transfected cells. Besides, genes encoding cell-cycle proteins, blood-related and cell differentiation-related proteins tended to be up-regulated after FDC-SP transfection, whereas cytokine/growth factors, signal transduction and metabolism-related genes tended to be down-regulated in hPDLCs overexpression FDC-SP.ConclusionsThe present study investigated FDC-SP's roles in hPDLCs' phenotype expression, via comparing the gene expression profiles between FDC-SP -transfected hPDLCs and empty vector-transfected cells upon microarray analysis. hPDLCs overexpression FDC-SP appear to display different gene expression patterns. In all, these observations showed a potential of FDC-SP in the maintenance of PDL homeostasis and its ultimate contribution to periodontal would-healing processes.
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Influence of Transmitted Virus on the Host's Immune Response: A Case Study
Viral Immunology , Vol. 0, No. 0.
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Angioscopy-guided selective aspiration thrombectomy for acute pulmonary thromboembolism
An 83-year-old woman with a history of pulmonary thromboembolism 10 years ago was referred for dyspnea. Anticoagulation therapy was terminated by her family doctor 3 years previously. On admission, D-dimer level was 16.6 µg/mL and arterial blood gas showed 88.1% on room air. Pulmonary arteriography (PAG) revealed some filling defects, mainly in the right interlobar artery (figure 1A). Non-obstructive angioscopy (NOA)1 showed two kinds of thrombi in the pulmonary arteries. At the translucent area, a massive, red, smooth thrombus was seen (figure 1B, video 1). Between the massive thrombus, floating, mobile, white-red, puff-like thrombi were demonstrated (figure 1C, video 2). As the thrombi entered the catheter spontaneously, aspiration was performed using a 20 mL syringe. Thrombi in the guiding catheter were collected by removing the guiding catheter. For the first trial, red thrombi were effectively aspirated (figure...
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Laryngocoele formation after ingestion of fish bone
Description
A 72-year-old man presented to the clinic with a 3-week history of anterior left neck pain. He described constant discomfort since eating fish a few weeks prior. He recalled pain at the time of eating, and felt he had ingested a fish bone.
There was no dysphagia, dyspnoea or haemoptysis on presentation. He had a medical history of type II diabetes mellitus, with no previous Ear, Nose and Throat issues.
Examination of the neck and oropharynx was normal. There were no palpable nodes or masses. Flexible nasendoscopy demonstrated a normal larynx. A lateral X-ray of the neck was arranged and showed no foreign body.
He was treated with simple analgesia and antacid, with a plan to review in 1 week.
He was reviewed and again examination and nasendoscopy were normal. CT scan revealed a traumatic laryngocoele at the left piriform sinus (figures 1 and 2).
...
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Traumatic phacocele: a rare but unique scenario
Description
The term phacocele is derived from a Greek word, where 'phaco' denotes lens and 'kele' meaning herniation. It is an unusual and very rare clinical condition.1
A 48-year-old male patient presented with sudden-onset diminution of vision, redness, pain in his left eye following blunt trauma 2 days ago. There was no significant ocular or systemic history. Visual acuity was perception of light positive with projection of rays accurate in left eye and 20/20 in right eye. On slit-lamp examination of the affected eye, there was a solid globular mass in the subconjunctival space located in the superonasal quadrant measuring 8x9 mm with smooth surface and rounded margins. There was an area of suspected scleral dehiscence, temporal to the mass lesion with uveal show (figure 1A). There was diffuse corneal oedema with descemet's folds. Anterior chamber detail was not clearly visible because of hyphaema (figure 1B). Intraocular pressure was 4 mm Hg....
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Severe medication-induced peripheral neuropathy treated with topical doxepin cream in a paediatric patient with leukaemia
A 17-year-old female with recently relapsed acute lymphoblastic leukaemia and a treatment course complicated by rhinocerebral mucormycosis infection developed severe peripheral neuropathy during the treatment for mucormycosis infection. This was felt to be a medication side effect. Her peripheral neuropathy was refractory to many well-established treatments, but ultimately responded dramatically and consistently to a novel therapy, topical doxepin cream (5%). This case report is the first published report of the application of topical doxepin cream for treatment of peripheral neuropathy in a paediatric patient.
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Systemic inflammatory response syndrome (SIRS) and a left bundle branch block (LBBB) due to nitrofurantoin
We present a case of a 74-year-old woman, who was on nitrofurantoin treatment for urinary tract infection (UTI), with fever and chills 7 hours after taking nitrofurantoin. She was hospitalised and evaluated for worsening UTI and sepsis. Initially, it appeared to be secondary to post-UTI sepsis because of possible resistant infection or conditions like pulmonary embolism or acute hepatitis. The patient also developed systemic inflammatory response syndrome, left bundle branch block (LBBB), thrombocytopaenia and transaminitis. Considering the side effects of nitrofurantoin, it was stopped. The patient showed improvement and recovered completely with symptomatic and supportive treatment. During follow-up visits with her primary care physician, thrombocytopaenia, transaminitisandLBBB were found to have been resolved.
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Actinomycosis presenting as an anterior abdominal mass after laparoscopic cholecystectomy
Abdominal actinomycosis is a rare disease caused by different anaerobic Actinomyces species. We report the case of a 55-year-old woman who presented with a painless, slow growing, left upper abdominal mass that developed after a laparoscopic cholecystectomy. A CT scan and MRI of the abdomen revealed a desmoid tumour of the left rectus abdominis muscle.
Surgical excision was performed with an uneventful postoperative course. The histological analysis of the specimen was inconsistent with a desmoid tumour and revealed an infection of Actinomyces israelii in the anterior abdominal wall that was confirmed with a microbiology culture. The surgical treatment was followed by a course of penicillin antibiotic therapy for 6 months. This treatment resulted in full recovery with no further complications. Although it is rare, the patient's history of laparoscopic cholecystectomy was identified as the likely source of infection.
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Pathological fracture of the femoral neck following septic coxitis and chronic osteomyelitis: a potential complication of Lemierres syndrome
We portray the case of a 16-year-old girl who was initially admitted to the paediatric emergency department with non-specific symptoms of a severe cold and was first treated symptomatically on an ambulatory basis. Within 6 days she developed the full clinical picture of Lemierre's syndrome with the extraordinary manifestation of involvement of her right hip. Despite an interdisciplinary coordinated treatment as well as surgical therapy, a full-blown sepsis evolved within a short time period and resulted in almost 2 months of intensive care. While the primary focus could be successfully controlled, a progressive avascular necrosis of the right proximal femur developed on the basis of a chronic osteomyelitis. This finally led to a pathological fracture of the femoral neck. After excluding the possibility of an enduring bacterial infection, the fracture was treated with a total hip replacement.
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Impella percutaneous left ventricular assist device for severe acute ischaemic mitral regurgitation as a bridge to surgery
Ischaemic papillary muscle rupture causing acute severe mitral regurgitation (MR) has a dramatic presentation and a very high mortality. Emergent surgical repair improves outcomes, which necessitates robust preoperative stabilisation. Here we discuss a patient with cardiogenic shock with an acute severe MR that was deemed very high risk for emergent valve replacement due to haemodynamic instability and respiratory failure. A percutaneous left ventricular assist device Impella 2.5 (Abiomed, Danvers, MA) drastically improved clinical status, and the patient underwent a successful surgical mitral valve replacement soon after placement of the temporary assist device. Our case highlights that percutaneous ventricular assist devices may help to stabilise patients with severe acute ischaemic MR, and it can serve as a bridge to surgery in high risk patients.
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Incidental discovery of a large complicated arteriovenous haemangioma
Arteriovenous haemangiomas within the chest are rare and uncommonly documented. After a 60-year-old woman with a history of smoking underwent a routine chest X-ray revealing a right apical mass, further investigations led to the discovery of a large extrapulmonary arteriovenous haemangioma in the superior mediastinum. Additionally, this case became complicated when the hemangioma was found to not only be compressing adjacent major arteries and veins, but also invading into the spinal canal and displacing the spinal cord. With multidisciplinary planning, the arteriovenous haemangioma was embolised and successfully resected. Thus, we present a case of an arteriovenous haemangioma in the superior mediastinum and discuss the importance of the case.
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Clostridium difficile extraintestinal abscess: a rare complication
Extraintestinal Clostridium difficile is rare. A 74-year-old man with a history of ulcerative colitis presented after a fall. Trauma work-up showed liver cirrhosis. Two days later he developed abdominal pain, distension, diarrhoea and leucocytosis. Stool tested positive for C. difficile. CT abdomen showed pancolitis with toxic megacolon. Total abdominal colectomy and ileostomy with a rectal stump was performed. He was discharged, but was readmitted with sepsis. CT abdomen showed a 10.4x7.2 cm fluid collection in the pelvis. C. difficile stool was negative. CT-guided abscess drainage grew C. difficile. Barium enema was negative for communication from the rectal stump to the abscess. The patient was treated with metronidazole for 2 weeks. In summary, extraintestinal C. difficile can develop from recent antibiotics use, gastrointestinal surgery and microperforations from toxic megacolon. We recommend abscess drainage, concomitant treatment with metronidazole and or vancomycin, and reimaging of abscess location 2–4 weeks after cessation of antibiotics.
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Non-surgical treatment of a relapsed cystic hygroma in an adult
Lymphatic malformations, also known as lymphangiomas or cystic hygromas, are benign masses that typically affect newborns and infants and involve the head and neck regions. They are, however, rare in adults and even rarer in the axillary region. Although surgery is considered to be the treatment of choice, we present a rare case of a recurrent cystic hygroma 32 years after the first surgical operation. Due to the cosmetic concerns and the risks of a surgical approach, non-surgical therapy with percutaneous sclerosants was performed, with a good outcome after a 2-year follow-up period.
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Native valve endocarditis caused by Lactococcus garvieae: an emerging human pathogen
A 57-year-old man presented with native mitral valve endocarditis caused by Lactococcus garvieae, a known animal pathogen that is increasingly being reported as a cause of human infections. The organism was cultured in four sets of blood cultures and identification was initially made by matrix-assisted laser desorption/ionisation—time of flight mass spectrometry and confirmed by 16S rDNA PCR of the blood culture isolate. He was successfully treated with 6 weeks of both amoxicillin and gentamicin and underwent valve replacement surgery after 4 weeks of antimicrobial treatment. The removed valve was sterile but L. garvieae DNA was detected on the valve using 16S rDNA PCR. The cause of the L. garvieae infection could not be ascertained but flexible sigmoidoscopy demonstrated colonic polyps, which have been linked to infection with this organism.
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Safe administration of S-1 after 5-fluorouracil-induced cardiotoxicity in a patient with colorectal cancer
Cardiotoxicity is a rare but challenging complication of 5-fluorouracil (5-FU) therapy. Compared with 5-FU, after application of S-1 lower plasma levels of the cardiotoxic metabolite alpha-fluoro-beta-alanine have been reported. Evidence for safe administration of S-1 following 5-FU cardiotoxicity is limited to a case report in an Asian patient. Herein we report the first case of S-1 application after 5-FU cardiotoxicity in a Caucasian patient.
A 67-year-old man with right-sided metastatic colorectal cancer and history of 5-FU cardiotoxicity had a progressive disease after 8-month therapy with irinotecan and bevacizumab. In consideration of known 5-FU cardiotoxicity, he was referred to our department for therapy counselling. We started a combination therapy with S-1, oxaliplatin and bevacizumab. The treatment was well tolerated without any cardiac problems.
Our report confirms the safety of S-1 in cases of 5-FU cardiotoxicity also in a Caucasian patient.
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Radiation-associated peritoneal angiosarcoma
Angiosarcomas account for only 1–2% of all soft tissue sarcomas, with the most common site of origin being in the head and neck region. Peritoneal angiosarcoma is an extremely rare tumour and few cases have been reported previously. Presentation of peritoneal angiosarcoma can be very variable, hence making diagnosis difficult. Herein, we review the current literature and describe a rare case of a patient who presented with haemorrhagic ascites, 17 years after radiotherapy for endometrial carcinoma and was subsequently diagnosed with peritoneal angiosarcoma. Due to extensive disease, surgery was not a viable option. She was started on palliative chemotherapy, but despite treatment, her condition deteriorated further and she eventually passed away. We highlight the diagnostic challenges and considerations in these patients as well as current treatment and management options available.
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Sesamoid osteonecrosis treated with radial extracorporeal shock wave therapy
Sesamoid osteonecrosis is a disabling condition resulting in severe forefoot pain, for which there are limited treatment options. We present a 52-year-old man with 1-year history of pain, aggravated by walking and playing tennis. On examination, pain was localised to plantar aspect of the first metatarsophalangeal joint. Imaging revealed evolving end-stage avascular necrosis of lateral sesamoid with early secondary degenerative changes. Previous exhaustive conservative treatment had been unsuccessful in alleviating his pain. As an alternative to surgery, radial extracorporeal shock wave therapy (rESWT) was proposed. Treatment protocol was 2000 pulses at frequency of 5 Hz, and pressure was varied from 1.2 to 1.8 bar according to patient tolerance. A total of eight sessions were delivered. At completion of treatment, the patient reported minimal discomfort to no pain and was able to return to playing tennis with no recurrence. We propose rESWT to be an effective novel conservative treatment for sesamoid osteonecrosis.
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Cardiac compression due to gastric volvulus: an unusual cause of chest pain
A 42-year-old man was admitted to coronary care for assessment with severe retrosternal chest pain. Echocardiography showed significant external compression of the left atrium. A subsequent CT scan revealed him to have a large hiatus hernia, with most of his stomach herniating into his thorax causing left atrial compression and gastric volvulus. He subsequently underwent successful emergency decompression of the gastric volvulus and repair of his hiatus hernia.
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A Syrian man with abdominal pain
A 32-year-old man presented with progressive abdominal pain, nausea and vomiting after swallowing a packet of dollar bills, his entire money savings, during his journey to Europe as a refugee. Subsequent imaging confirmed the presence of a foreign body in his stomach, which required surgical intervention to be removed. This is one of many cases that illustrate the hopeless circumstances people in the Middle-Eastern warzone are currently facing.
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'The dark pancreas: classic CT appearance of total pancreatic lipomatosis
Description
A 31-year-old male patient presented with a history of chronic abdominal pain and progressive loss of weight. Patient also had massive steatorrhea and had been a chronic alcoholic. There was no history of diabetes mellitus, tuberculosis or hypertension. Laboratory investigations revealed profound hypoproteinaemia. Patient underwent a contrast-enhanced CT of the abdomen. It demonstrated a striking 'dark' pancreas showing an attenuation of –88 Hounsfield units corresponding to fat (figure 1). No obvious enhancing solid component was seen. Careful review of the multiplanar CT reconstruction images confirmed the presence of dilated pancreatic duct with multiple intraductal calculi (figure 2). The CT findings were diagnostic of total pancreatic lipomatosis secondary to obstructed pancreatic ductal system by calculi/chronic calcific pancreatitis. Patient was managed conservatively using pancreatic enzyme replacement therapy.
Figure 1
Axial contrast-enhanced CT image shows the dark, hypoattenuating pancreatic parenchyma corresponding to fat. Note the...
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Caution advised with dapagliflozin in the setting of male urinary tract outlet obstruction
We describe an adverse outcome in a 70-year-old man with type 2 diabetes mellitus treated with sodium–glucose cotransporter type 2 (SGLT2) inhibitor dapagliflozin. SGLT2 inhibitors act in the proximal tubules to prevent glucose reabsorption and induce urinary glucose excretion, they have been associated with increased risk of urinary tract infection (UTI). Our patient presented to hospital with Escherichia coli septicaemia with positive urine and blood cultures on the background of two previous UTIs occurring post commencement of dapagliflozin in the community. Renal tract ultrasound in hospital revealed incomplete bladder emptying with evidence of urinary stasis, and a postvoid residual volume of 180 mL. His dapagliflozin was ceased, and he has had no further episodes of UTI. This case suggests there may be an increased risk of UTI in patients prescribed SGLT2 inhibitors who also have evidence of bladder outlet obstruction—caution is advised in the prescribing of SGLT2 inhibitors in this setting.
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Back pain and oedematous Schmorl node: a diagnostic dilemma
A 26-year-old female from India presented with progressive, unremitting low back pain for over 1 year. She had been treated unsuccessfully for left-sided sacroiliitis, pelvic floor dysfunction, ankylosing spondylitis and seronegative spondyloarthritis. MRI lumbar spine showed a Schmorl node with surrounding marrow oedema at L4, the relevance of which is not clear in literature. One year after initial presentation, a biopsy of this lesion revealed culture positive diagnosis of spinal tuberculosis. Despite advances in imaging, delayed diagnosis is not uncommon in spinal tuberculosis (TB). In our case, it was also attributed to an unknown early lesion: Schmorl node with surrounding oedema. Any association of this lesion with spinal TB has previously not been reported.
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Metabolic Syndrome Among Leukemia Survivors: Still Delineating the Risk
Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.
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Postoperative Outcomes in Graves' Disease Patients: Results from the Nationwide Inpatient Sample Database
Thyroid , Vol. 0, No. 0.
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Iodine Storage and Metabolism of Mild to Moderate Iodine-Deficient Pregnant Rats
Thyroid , Vol. 0, No. 0.
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Relationship between various anthropometric measures and apnea-hypopnea index in Korean men
Source:Auris Nasus Larynx
Author(s): Jeong-Hong Kim, Yong Cheol Koo, Hyung Ju Cho, Ju Wan Kang
ObjectiveBody mass index (BMI) has been shown to be strongly correlated with severity of OSA. However, BMI has not been shown to be correlated with sleep apnea in all patients studied. The purpose of this study was to evaluate the relationship between various anthropometric measures and severity of OSA according to BMI in men.MethodsWe conducted a retrospective analysis of the medical records of patients who visited for evaluation of OSA. Polysomnography results, height, weight, neck circumference, waist circumference, and hip circumference were obtained in all subjects. BMI, body adiposity index, waist to hip ratio, and waist to height ratio were also calculated.ResultsA total of 195 male participants were included in the final analysis. BMI showed the strongest correlation with AHI in all subjects. In 125 participants with a BMI of 25 or more, BMI was most strongly correlated with high AHI compared to other measurements. However, waist to hip ratio showed the strongest correlation with AHI in 70 participants with a BMI of less than 25 and, in this group, BMI did not show significant correlation with AHI.ConclusionConsiderations about anthropometric measurements in OSA patients should differ according to degree of obesity or BMI.
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Antiviral activity of phenanthrenes from the medicinal plant Bletilla striata against influenza A virus
Influenza represents a serious public health concern. The emergence of resistance to anti-influenza drugs underlines the need to develop new drugs. This study aimed to evaluate the anti-influenza viral activit...
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Clinical outcomes in children with Henoch–Schönlein purpura nephritis without crescents
Abstract
Background
Henoch–Schönlein purpura is the most common vasculitis in children. Its long-term prognosis depends on renal involvement. The management of Henoch–Schönlein purpura nephritis (HSPN) remains controversial. This study reports the prognosis of children with HSPN presenting with class 2 International Study of Kidney Disease in Children (ISKDC) nephritis.
Methods
All children with HSPN class 2 diagnosed between 1995 and 2015 in four pediatric nephrology centers were included, and clinical and biological data were collected from the medical files. The primary endpoint was proteinuria remission defined as a proteinuria <200 mg/L.
Results
Ninety-two children were included in the study with a median follow-up of 36 (6–120) months; 28% had nephrotic syndrome, 31% proteinuria >3 g/L, 52% proteinuria between 1 and 3 g/L, and 18% proteinuria <1 g/L. Forty-seven percent of patients received orally treatment with steroids alone, 37% received methylprednisolone pulses followed by steroids orally, 18% received no steroids. Although 85% reached remission during follow-up, 12% did not maintain complete remission over time so that only 75% remained in complete remission by the end of the follow-up. Univariate analysis found a higher likelihood of remission in patients with higher proteinuria at disease onset (p = 0.009). This trend was not found in the multivariate analysis after adjusting for treatments, as patients with higher proteinuria were most often treated with steroids.
Conclusion
Our study shows that one fourth of patients with HSPN class 2 remain proteinuric and thus carry the risk of developing chronic kidney disease over the long term. This finding, together with the better outcome of patients treated with steroids, is in favor of using high-dose steroids orally or IV in these patients.
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The ongoing saga of the mechanism(s) of MHC class I-restricted cross-presentation
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Metabolic signatures of T-cells and macrophages in rheumatoid arthritis
Cornelia M Weyand | Markus Zeisbrich | Jörg J Goronzy
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mTOR signaling in the differentiation and function of regulatory and effector T cells
Hu Zeng | Hongbo Chi
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A systematic review and meta-analysis of long-term studies (five or more years) assessing maxillary sinus floor augmentation
Publication date: Available online 22 May 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): T. Starch-Jensen, H. Aludden, M. Hallman, C. Dahlin, A.-E. Christensen, A. Mordenfeld
The objective was to test the hypothesis of no difference in long-term (≥5 years) implant treatment outcomes after maxillary sinus floor augmentation (MSFA) with autogenous bone graft compared to a mixture of autogenous bone graft and bone substitutes or bone substitutes alone. A MEDLINE (PubMed), Embase, and Cochrane Library search in combination with a hand-search of relevant journals was conducted. Human studies published in English between January 1, 1990 and October 1, 2016 were included. Nine studies fulfilled the inclusion criteria. The survival of suprastructures has never been compared within the same study. The 5-year implant survival after MSFA with autogenous bone graft was 97%, compared to 95% for Bio-Oss; the reduction in vertical height of the augmented sinus was equivalent with the two treatment modalities. Non-comparative studies demonstrated high survival rates for suprastructures and implants regardless of the grafting material used. Meta-analysis revealed an overall estimated patient-based implant survival of 95% (confidence interval 0.92–0.96). High implant stability quotient values, high patient satisfaction, and limited peri-implant marginal bone loss were revealed in non-comparative studies. No long-term randomized controlled trial comparing the different treatment modalities was identified. Hence, the conclusions drawn from the results of this systematic review should be interpreted with caution.
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"I feel my arm shaking": Partial cataplexy mistaken for drug-resistant focal epilepsy
There is often a considerable delay in the diagnosis of narcolepsy1,2. This is partly due to the insidious nature of disease onset and incomplete presence of characteristic symptoms2. Moreover, narcolepsy may mimic other neurological diseases (in particular, epilepsy) due to the presence of paroxysmal events3. Epilepsy, which is much more prevalent, might thus appear as a straightforward diagnosis, especially if the symptoms are focal and associated with abnormal movements or jerks.table 1.
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Rapid molecular sexing of three-spined sticklebacks, Gasterosteus aculeatus L., based on large Y-chromosomal insertions
Abstract
There is a need for rapid and reliable molecular sexing of three-spined sticklebacks, Gasterosteus aculeatus, the supermodel species for evolutionary biology. A DNA region at the 5′ end of the sex-linked microsatellite Gac4202 was sequenced for the X chromosome of six females and the Y chromosome of five males from three populations. The Y chromosome contained two large insertions, which did not recombine with the phenotype of sex in a cross of 322 individuals. Genetic variation (SNPs and indels) within the insertions was smaller than on flanking DNA sequences. Three molecular PCR-based sex tests were developed, in which the first, the second or both insertions were covered. In five European populations (from DE, CH, NL, GB) of three-spined sticklebacks, tests with both insertions combined showed two clearly separated bands on agarose minigels in males and one band in females. The tests with the separate insertions gave similar results. Thus, the new molecular sexing method gave rapid and reliable results for sexing three-spined sticklebacks and is an improvement and/or alternative to existing methods.
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Circulating tumor DNA profiling reveals clonal evolution and real-time disease progression in advanced hepatocellular carcinoma
Abstract
Circulating tumor DNA (ctDNA) provides a potential non-invasive biomarker for cancer diagnosis and prognosis, but whether it could reflect tumor heterogeneity and monitor therapeutic responses in hepatocellular carcinoma (HCC) is unclear. Focusing on 574 cancer genes known to harbor actionable mutations, we identified the mutation repertoire of HCC tissues, and monitored the corresponding ctDNA features in blood samples to evaluate its clinical significance. Analysis of 3 HCC patients' mutation profiles revealed that ctDNA could overcome tumor heterogeneity and provide information of tumor burden and prognosis. Further analysis was conducted on the 4th HCC case with multiple lesion samples and sequential plasma samples. We identified 160 subclonal SNVs in tumor tissues as well as matched peritumor tissues with PBMC as control. 96.9% of this patient's tissue mutations could be also detected in plasma samples. These subclonal SNVs were grouped into 9 clusters according to their trends of cellular prevalence shift in tumor tissues. Two clusters constituted of tumor stem somatic mutations showed circulating levels relating with cancer progression. Analysis of tumor somatic mutations revealed that circulating level of such tumor stem somatic mutations could reflect tumor burden and even predict prognosis earlier than traditional strategies. Furthermore, HCK (p.V174M), identified as a recurrent/metastatic related mutation site, could promote migration and invasion of HCC cells. Taken together, study of mutation profiles in biopsy and plasma samples in HCC patients showed that ctDNA could overcome tumor heterogeneity and real-time track the therapeutic responses in the longitudinal monitoring. This article is protected by copyright. All rights reserved.
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Hepcidin levels and gastric cancer risk in the EPIC-EurGast Study
Abstract
Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated.
After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5ng/l = 0.96, 95% CI = 0.93-0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a non-significant 38% (95% CI: -69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis. This article is protected by copyright. All rights reserved.
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The accuracy of three-dimensional prediction of soft tissue changes following the surgical correction of facial asymmetry: An innovative concept
Publication date: Available online 22 May 2017
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): T. Mundluru, A. Almukhtar, X. Ju, A. Ayoub
The accuracy of three-dimensional (3D) predictions of soft tissue changes in the surgical correction of facial asymmetry was evaluated in this study. Preoperative (T1) and 6–12-month postoperative (T2) cone beam computed tomography scans of 13 patients were studied. All patients underwent surgical correction of facial asymmetry as part of a multidisciplinary treatment protocol. The magnitude of the surgical movement was measured; virtual surgery was performed on the preoperative scans using Maxilim software. The predicted soft tissue changes were compared to the actual postoperative appearance (T2). Mean (signed) distances and mean (absolute) distances between the predicted and actual 3D surface meshes for each region were calculated. The one-sample t-test was applied to test the alternative hypothesis that the mean absolute distances had a value of <2.0mm. A novel directional analysis was applied to analyse the accuracy of the prediction of soft tissue changes. The results showed that the distances between the predicted and actual postoperative soft tissue changes were less than 2.0mm in all regions. The predicted facial morphology was narrower than the actual surgical changes in the cheek regions. 3D soft tissue prediction using Maxilim software in patients undergoing the correction of facial asymmetry is clinically acceptable.
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Masterplan Medizinstudium 2020
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 313-313
DOI: 10.1055/s-0043-109409
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
http://ift.tt/2rvePk6
Wiederaufnahme auf die Intensivstation taugt nicht als Prognosekriterium
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 317-317
DOI: 10.1055/s-0043-109144
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
http://ift.tt/2rv0Hac
Infusionsmenge korreliert mit interstitieller Flüssigkeitsansammlung
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 320-321
DOI: 10.1055/s-0043-108530
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
http://ift.tt/2rux5tS
Immer wichtiger in Zeiten der Multiresistenz
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 322-322
DOI: 10.1055/s-0042-122774
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
http://ift.tt/2ruvww4
Präoperative Vorbereitung: Optimierung pulmonaler Erkrankungen
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 356-366
DOI: 10.1055/s-0042-108926
Lungenerkrankungen wie COPD oder Asthma sind bedeutende Risikofaktoren perioperativer pulmonaler Komplikationen. Die Optimierung dieser Erkrankungen ist deshalb wichtiger Bestandteil des präoperativen Managements. Das Wissen um die Pathophysiologie und medikamentöse Therapie ist dabei essenziell.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2ruRT49
Vibrationstraining zur Verbesserung der Critical-Illness-Myopathie?
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 317-318
DOI: 10.1055/s-0043-109145
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
http://ift.tt/2ruRTkF
Präoperative Vorbereitung: Patient Blood Management – Was ist optimal?
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 326-340
DOI: 10.1055/s-0042-108925
Patient Blood Management (PBM) fokussiert auf ein umfassendes Anämiemanagement, die Minimierung (unnötiger) iatrogener Blutverluste und die Ausschöpfung der natürlichen Anämietoleranz mit rationalem Einsatz von Erythrozytenkonzentrat-Transfusionen. Im Mittelpunkt des aktuellen Beitrags stehen die in der präoperativen Phase entscheidenden PBM-Komponenten: Management einer Anämie, prätransfusionelle Vorbereitungen und Management von Antikoagulanzien. Die präoperative Anämie ist ein unabhängiger Risikofaktor für eine erhöhte perioperative Morbidität und Sterblichkeit. Zum frühestmöglichen Zeitpunkt sollte daher vor elektiven Eingriffen die Ursachen der Anämie abgeklärt und bei behandelbaren Ursachen der Anämie eine spezifische Behandlung eingeleitet werden. Die präoperative prätransfusionelle Analytik sollte in Abhängigkeit von der Transfusionswahrscheinlichkeit (und dem Ausgangshämoglobinwert) einem Stufenkonzept folgen und aktuelle hausinterne Daten berücksichtigen. Im Umgang mit (oralen) Antikoagulanzien sollte bereits in der präoperativen Phase eine individuelle Risikostratifizierung erfolgen. Anhand des individuellen Blutungs- und Thromboembolierisikos wird sodann entschieden, ob die Medikation fortgeführt, pausiert oder überbrückt werden muss. Ohne klar definierte Verantwortlichkeiten im präoperativen PBM-Team, Kommunikation und Schulung aller Beteiligten ist langfristig kein Erfolg des präoperativen PBM-Programms zu erwarten.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2ruQxqe
ECMO-Therapie: Langzeitüberleben bei respiratorischem Versagen
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 318-319
DOI: 10.1055/s-0043-109143
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
http://ift.tt/2rv4lkJ
Kasuistik: ECMO-Einsatz bei hyperkapnischer Hirndruckkrise
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 376-381
DOI: 10.1055/s-0043-103506
Unter der Geburt trübte sich bei einer 29-jährigen Patientin die Vigilanz progredient bis zum Koma. Grund war eine schwere Hirnblutung als Komplikation eines bis dahin nicht erkennbaren HELLP-Syndroms. Nach der zerebralen OP entwickelte die Patientin aggravierend ein schweres ARDS mit Hyperkapnie und kritischem Anstieg des intrakraniellen Druckes. Trotz Kontraindikation war eine ECMO-Therapie für insgesamt 31 Tage letztlich erfolgreich.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2ruWLq5
Traumapatienten: niedrigere Mortalität unter NOAKs als unter Warfarin
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 319-320
DOI: 10.1055/s-0043-105635
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
http://ift.tt/2ruQyKO
Präoperative Vorbereitung
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 324-325
DOI: 10.1055/s-0043-108751
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
http://ift.tt/2rv0Tqc
Präoperative Vorbereitung und Evaluation: der ältere Patient
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 342-355
DOI: 10.1055/s-0042-109286
Aufgrund der steigenden Lebenserwartung müssen sich heutzutage immer mehr ältere und hochbetagte Patienten einer Operation unterziehen – eine Herausforderung für die Chirurgie und insbesondere für die Anästhesiologie. Dieser Beitrag beschreibt, wie altersbedingte Besonderheiten präoperativ erfasst und entsprechende Maßnahmen eingeleitet werden können, um das Risiko der postoperativen Morbidität – oder gar Pflegebedürftigkeit – zu verringern.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2qaCr9O
Guter Einstieg
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 322-322
DOI: 10.1055/s-0042-108793
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
http://ift.tt/2rv6NYn
Akutschmerztherapie bei Appendektomie
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 367-374
DOI: 10.1055/s-0043-104599
Schmerztherapie spielt in der Chirurgie eine zentrale Rolle. Eine strukturierte Akutschmerztherapie verbessert unmittelbar die Lebensqualität, senkt mittelfristig die Morbidität und verhindert langfristig eine Schmerzchronifizierung – bei deutlichen ökonomischen Vorteilen wie reduzierter Krankenhausverweildauer und kürzerem Krankenstand. Diese 4 Aspekte werden oft und gerade bei scheinbar „kleinen Operationen" stiefmütterlich behandelt.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2qbcFSM
Pssst … AINS-Secrets: Heute aus der Traumatologie und Orthopädie
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 382-386
DOI: 10.1055/s-0042-101659
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
http://ift.tt/2qb9hHm
Neuroimaging Biomarkers and Impaired Olfaction in Cognitively Normal Individuals
Abstract
Objective: There is a need for inexpensive non-invasive tests to identify older healthy persons at risk for Alzheimer's disease (AD) for enrollment in AD prevention trials. Our objective was to examine whether abnormalities in neuroimaging measures of amyloid and neurodegeneration are correlated with odor identification (OI) in the population-based Mayo Clinic Study of Aging (MCSA).
Methods: Cognitively normal (CN) participants had olfactory function assessed using the Brief Smell Identification Test (B-SIT), underwent magnetic resonance imaging (MRI; n=829) to assess a composite Alzheimer's disease (AD) signature cortical thickness and hippocampal volume (HVa), and, 11C-Pittsburgh compound B (11C-PiB; n=306) and 18fluorodeoxyglucose (18F-FDG; n=305) positron emission tomography (PET) scanning to assess amyloid accumulation and brain hypometabolism, respectively. The association of neuroimaging biomarkers with OI was examined using multinomial logistic regression and simple linear regression models adjusted for potential confounders.
Results: Among 829 CN participants (mean age 79.2 years; 51.5% men), 248 (29.9%) were normosmic and 78 (9.4%) had anosmia (B-SIT score <6). Abnormal AD signature cortical thickness and reduced HVa were associated with decreased OI as a continuous measure (slope=-.43; (95%CI -.77, -.09); p=.01 and slope=-.72; (95%CI -1.15, -.28); <.01, respectively). Reduced HVa, decreased AD signature cortical thickness and increased amyloid accumulation were significantly associated with increased odds of anosmia.
Interpretation: Our findings suggest that OI may be a non-invasive, inexpensive marker for risk stratification, for identifying participants at the preclinical stage of AD who may be at risk for cognitive impairment, and eligible for inclusion in AD prevention clinical trials. These cross-sectional findings remain to be validated prospectively. This article is protected by copyright. All rights reserved.
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ECMO-Therapie: Langzeitüberleben bei respiratorischem Versagen
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 318-319
DOI: 10.1055/s-0043-109143
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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The repetition of behavioral assessments in diagnosis of disorders of consciousness
Abstract
Objective: To determine whether repeated examinations using the Coma Recovery Scale-Revised have an impact on diagnostic accuracy of patients with disorders of consciousness and to provide guidelines regarding the number of assessments required for obtaining a reliable diagnosis.
Methods: 123 adult patients with chronic disorders of consciousness were referred to our tertiary center. They were assessed at least 6 times with the Coma Recovery Scale-Revised within a 10-day period. Clinical diagnoses based on 1, 2, 3, 4, and 5 Coma Recovery Scale-Revised assessments were compared with a reference diagnosis (i.e., the highest behavioral diagnosis obtained after 6 evaluations) using non-parametric statistics. Results were considered significant at P<0.05 corrected for multiple comparisons.
Results: The number of assessments had a significant effect on the clinical diagnosis. Up to the fourth examination, the diagnosis was still statistically different from the reference diagnosis based on 6 CRS-R assessments. Compared to this reference diagnosis, the first evaluation led to 36% of misdiagnoses.
Interpretation: The number of Coma Recovery Scale-Revised assessments has an impact on the clinical diagnosis of patients with chronic disorders of consciousness. Up to the fourth examinations, behavioral fluctuations may still impact the diagnostic accuracy. We here suggest performing at least 5 assessments in each patient with disorders of consciousness within a short time interval (e.g., 2 weeks) to reduce misdiagnosis. This article is protected by copyright. All rights reserved.
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Kasuistik: ECMO-Einsatz bei hyperkapnischer Hirndruckkrise
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 376-381
DOI: 10.1055/s-0043-103506
Unter der Geburt trübte sich bei einer 29-jährigen Patientin die Vigilanz progredient bis zum Koma. Grund war eine schwere Hirnblutung als Komplikation eines bis dahin nicht erkennbaren HELLP-Syndroms. Nach der zerebralen OP entwickelte die Patientin aggravierend ein schweres ARDS mit Hyperkapnie und kritischem Anstieg des intrakraniellen Druckes. Trotz Kontraindikation war eine ECMO-Therapie für insgesamt 31 Tage letztlich erfolgreich.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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The Missing, The Short, and The Long: L-Dopa Responses and Dopamine Actions
Abstract
We attempt to correlate the clinical pharmacology of dopamine replacement therapy (DRT) in Parkinson Disease with known features of striatal dopamine actions. Despite its obvious impact, DRT does not normalize motor function, likely due to disrupted phasic dopaminergic signaling. The DRT Short Duration Response is likely a permissive-paracrine effect, possibly resulting from dopaminergic support of corticostriate synaptic plasticity. The DRT Long Duration Response may result from mimicry of tonic dopamine signaling regulation of movement vigor. Our understanding of dopamine actions does not explain important aspects of DRT clinical pharmacology. Reducing these knowledge gaps provides opportunities to improve understanding of dopamine actions and symptomatic treatment of Parkinson disease. This article is protected by copyright. All rights reserved.
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Immer wichtiger in Zeiten der Multiresistenz
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 322-322
DOI: 10.1055/s-0042-122774
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Wiederaufnahme auf die Intensivstation taugt nicht als Prognosekriterium
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 317-317
DOI: 10.1055/s-0043-109144
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Präoperative Vorbereitung: Optimierung pulmonaler Erkrankungen
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 356-366
DOI: 10.1055/s-0042-108926
Lungenerkrankungen wie COPD oder Asthma sind bedeutende Risikofaktoren perioperativer pulmonaler Komplikationen. Die Optimierung dieser Erkrankungen ist deshalb wichtiger Bestandteil des präoperativen Managements. Das Wissen um die Pathophysiologie und medikamentöse Therapie ist dabei essenziell.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Vibrationstraining zur Verbesserung der Critical-Illness-Myopathie?
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 317-318
DOI: 10.1055/s-0043-109145
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Präoperative Vorbereitung: Patient Blood Management – Was ist optimal?
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 326-340
DOI: 10.1055/s-0042-108925
Patient Blood Management (PBM) fokussiert auf ein umfassendes Anämiemanagement, die Minimierung (unnötiger) iatrogener Blutverluste und die Ausschöpfung der natürlichen Anämietoleranz mit rationalem Einsatz von Erythrozytenkonzentrat-Transfusionen. Im Mittelpunkt des aktuellen Beitrags stehen die in der präoperativen Phase entscheidenden PBM-Komponenten: Management einer Anämie, prätransfusionelle Vorbereitungen und Management von Antikoagulanzien. Die präoperative Anämie ist ein unabhängiger Risikofaktor für eine erhöhte perioperative Morbidität und Sterblichkeit. Zum frühestmöglichen Zeitpunkt sollte daher vor elektiven Eingriffen die Ursachen der Anämie abgeklärt und bei behandelbaren Ursachen der Anämie eine spezifische Behandlung eingeleitet werden. Die präoperative prätransfusionelle Analytik sollte in Abhängigkeit von der Transfusionswahrscheinlichkeit (und dem Ausgangshämoglobinwert) einem Stufenkonzept folgen und aktuelle hausinterne Daten berücksichtigen. Im Umgang mit (oralen) Antikoagulanzien sollte bereits in der präoperativen Phase eine individuelle Risikostratifizierung erfolgen. Anhand des individuellen Blutungs- und Thromboembolierisikos wird sodann entschieden, ob die Medikation fortgeführt, pausiert oder überbrückt werden muss. Ohne klar definierte Verantwortlichkeiten im präoperativen PBM-Team, Kommunikation und Schulung aller Beteiligten ist langfristig kein Erfolg des präoperativen PBM-Programms zu erwarten.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Traumapatienten: niedrigere Mortalität unter NOAKs als unter Warfarin
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 319-320
DOI: 10.1055/s-0043-105635
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Präoperative Vorbereitung
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 324-325
DOI: 10.1055/s-0043-108751
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Infusionsmenge korreliert mit interstitieller Flüssigkeitsansammlung
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 320-321
DOI: 10.1055/s-0043-108530
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Präoperative Vorbereitung und Evaluation: der ältere Patient
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 342-355
DOI: 10.1055/s-0042-109286
Aufgrund der steigenden Lebenserwartung müssen sich heutzutage immer mehr ältere und hochbetagte Patienten einer Operation unterziehen – eine Herausforderung für die Chirurgie und insbesondere für die Anästhesiologie. Dieser Beitrag beschreibt, wie altersbedingte Besonderheiten präoperativ erfasst und entsprechende Maßnahmen eingeleitet werden können, um das Risiko der postoperativen Morbidität – oder gar Pflegebedürftigkeit – zu verringern.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Guter Einstieg
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 322-322
DOI: 10.1055/s-0042-108793
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Akutschmerztherapie bei Appendektomie
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 367-374
DOI: 10.1055/s-0043-104599
Schmerztherapie spielt in der Chirurgie eine zentrale Rolle. Eine strukturierte Akutschmerztherapie verbessert unmittelbar die Lebensqualität, senkt mittelfristig die Morbidität und verhindert langfristig eine Schmerzchronifizierung – bei deutlichen ökonomischen Vorteilen wie reduzierter Krankenhausverweildauer und kürzerem Krankenstand. Diese 4 Aspekte werden oft und gerade bei scheinbar „kleinen Operationen" stiefmütterlich behandelt.
[...]
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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Pssst … AINS-Secrets: Heute aus der Traumatologie und Orthopädie
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 382-386
DOI: 10.1055/s-0042-101659
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Masterplan Medizinstudium 2020
Anästhesiol Intensivmed Notfallmed Schmerzther 2017; 52: 313-313
DOI: 10.1055/s-0043-109409
Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
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Augmentation de la projection du mamelon dans les reconstructions mammaires par injection de derme artificiel
Source:Annales de Chirurgie Plastique Esthétique
Author(s): A. Serre, D. Guillier, V. Moris, K. Rem, M. Revol, C. François, S. Cristofari
IntroductionLa reconstruction de la plaque aréolomamelonnaire (Pam) est la dernière étape et un point clé de la reconstruction mammaire. La technique doit être adaptée aux étapes précédentes de reconstruction pour éviter toutes complications et en particulier l'exposition d'un implant, surtout en terrain irradié. Le lambeau dermique pur peut être indiqué pour la reconstruction du mamelon après reconstruction mammaire par implant après radiothérapie. Sa limite est l'hypoprojection du mamelon. Nous proposons d'évaluer l'augmentation de projection du mamelon, reconstruit par lambeau dermique pur, par injection d'Integra® Flowable Wound Matrice (Integra LifeSciences®, Plainsboro, New Jersey).Patients et méthodeLa projection des mamelons reconstruits par lambeau dermique pur a été mesurée avant, après et à 6mois de l'injection d'Integra Flowable Wound Matrice sur des patientes inclues de février à mars 2016. La satisfaction des patientes et les complications ont été évaluées rétrospectivement.RésultatsDixpatientes âgées de 55ans en moyenne ont été incluses, avec un délai moyen de 19mois (7mois à 33mois) entre la reconstruction du mamelon par lambeau dermique pur et l'injection. Un volume de 1 à 1,6cc était injecté. Une augmentation de projection significative, en moyenne de 2mm à 6mois a été mesurée (1,5mm à 2,5mm, p<0,01), sans complication, avec un taux de satisfaction de 4,5/5.ConclusionL'injection de derme artificiel type Integra® Flowable Wound Matrice paraît efficace pour augmenter la projection des mamelons reconstruits par lambeau dermique pur après reconstruction mammaire et ce sans complication.IntroductionThe reconstruction of the Nipple-Areola Complex (NAC) is the last step and a key part in breast reconstruction. The technique to be used should be chosen as to avoid any complications on previous reconstruction steps. The use of local flaps for NAC reconstruction could be associated with implant exposure especially in the presence of a history of radiation therapy. The pure dermal flap could be indicated for the nipple reconstruction after breast reconstruction by implant after radiotherapy. The limit stay in the nipple hypoprojection. We suggest to assess the increase of the nipple projection, reconstructed by pure dermal flap, by injection of Integra® Flowable Wound Matrix (Integra LifeSciences®, Plainsboro, New jersey).Patients and methodNipple projection has been measured among patients enclosed from february to March 2016 reconstructed by pure dermal flap: before, after and also at a 6months term from the injection of Integra® Flowable Wound Matrix. Patient satisfaction and complications have been measured retrospectively.ResultsTen patients with an average of 55years have been enclosed, with an average limit of time of 19months (7 to 33months) between the breast nipple reconstruction by dermal flap and the injection. A volume of 1 to 1.6cc has been injected. A significative increase projection of 2mm at a 6months term has been measured (1.5 to 2.5mm, P<0.01), without complication and a satisfaction rate of 4.5/5.ConclusionThe injection of an artificial derm-like Integra® Flowable Wound Matrix seems to be efficient to increase the nipple projection reconstructed by pure dermal flap after a breast reconstruction and moreover, without complications.
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Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma
Asthma is a common chronic inflammatory disease of the airways that affects an estimated 315 million persons worldwide. Approximately 5 to 10% of persons with asthma have a severe form of disease that is usually managed with high-dose inhaled glucocorticoids and bronchodilators. Within this group,…
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Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma
Asthma is a common chronic inflammatory disease of the airways that affects an estimated 315 million persons worldwide. Approximately 5 to 10% of persons with asthma have a severe form of disease that is usually managed with high-dose inhaled glucocorticoids and bronchodilators. Within this group,…
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Validation of the Social support and Pain Questionnaire (SPQ) in patients with painful temporomandibular disorders
The present study aimed to validate of Social support and Pain Questionnaire (SPQ) for use in Chinese patients with painful temporomandibular disorders (TMD).
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Second Harmonic Generation Guided Raman Spectroscopy for Sensitive Detection of Polymorph Transitions
Analytical Chemistry
DOI: 10.1021/acs.analchem.7b00431
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IFC-EDITORIAL BOARD
Source:Research in Developmental Disabilities, Volume 65
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The Cost of Relapse in Schizophrenia
Abstract
Introduction
Schizophrenia is a chronic and debilitating mental illness characterised by periods of relapse that require resource intensive management. Quantifying the cost of relapse is central to the evaluation of the cost effectiveness of treating schizophrenia.
Objectives
We aimed to undertake a comprehensive search of the available literature on the cost of relapse.
Methods
We performed a search on multiple databases (MEDLINE, Embase, PsycINFO and Health Management Information Consortium) for any study reporting a cost of relapse or data from which such a cost could be calculated. Costs are reported in 2015 international dollars.
Results
We found 16 studies reporting costs associated with relapse over a defined period of time and identified a cost associated with hospitalisation for relapse in 43 studies. Eight clinical decision analyses also provided cost estimates. Studies from the US report excess costs of relapse of $6033–$32,753 (2015 Purchasing Power Parity dollars [PPP$]) over periods of 12–15 months. European studies report excess costs of $8665–$18,676 (2015 PPP$) over periods of 6–12 months. Estimates of the cost of hospitalisation for relapse are more diverse, and associated with marked differences in typical length of stay across jurisdictions.
Conclusions
Wide ranges in the estimated cost of relapse may reflect differences in sample section and relapse definition as well as practice styles and differences in resource costs. Selection of the most appropriate cost estimate should be guided by the definition of relapse and the analysis setting.
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Paramedic - Pella Community Ambulance
Private non-profit community based ambulance service is currently accepting applications for a full-time paramedic position. Must have current valid NREMT and Iowa Paramedic certification in good standing, current AHA BLS and ACLS certification, be able to successfully complete a pre-employment screening and thorough background check. Must possess valid driver's license with excellent driving history ...
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Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma
Asthma is a common chronic inflammatory disease of the airways that affects an estimated 315 million persons worldwide. Approximately 5 to 10% of persons with asthma have a severe form of disease that is usually managed with high-dose inhaled glucocorticoids and bronchodilators. Within this group,…
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Automated algorithm for counting microbleeds in patients with familial cerebral cavernous malformations
Abstract
Purpose
Familial cerebral cavernous malformation (CCM) patients present with multiple lesions that can grow both in number and size over time and are reliably detected on susceptibility-weighted imaging (SWI). Manual counting of lesions is arduous and subject to high variability. We aimed to develop an automated algorithm for counting CCM microbleeds (lesions <5 mm in diameter) on SWI images.
Methods
Fifty-seven familial CCM type-1 patients were included in this institutional review board-approved study. Baseline SWI (n = 57) and follow-up SWI (n = 17) were performed on a 3T Siemens MR scanner with lesions counted manually by the study neuroradiologist. We modified an algorithm for detecting radiation-induced microbleeds on SWI images in brain tumor patients, using a training set of 22 manually delineated CCM microbleeds from two random scans. Manual and automated counts were compared using linear regression with robust standard errors, intra-class correlation (ICC), and paired t tests. A validation analysis comparing the automated counting algorithm and a consensus read from two neuroradiologists was used to calculate sensitivity, the proportion of microbleeds correctly identified by the automated algorithm.
Results
Automated and manual microbleed counts were in strong agreement in both baseline (ICC = 0.95, p < 0.001) and longitudinal (ICC = 0.88, p < 0.001) analyses, with no significant difference between average counts (baseline p = 0.11, longitudinal p = 0.29). In the validation analysis, the algorithm correctly identified 662 of 1325 microbleeds (sensitivity=50%), again with strong agreement between approaches (ICC = 0.77, p < 0.001).
Conclusion
The automated algorithm is a consistent method for counting microbleeds in familial CCM patients that can facilitate lesion quantification and tracking.
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Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma
Asthma is a common chronic inflammatory disease of the airways that affects an estimated 315 million persons worldwide. Approximately 5 to 10% of persons with asthma have a severe form of disease that is usually managed with high-dose inhaled glucocorticoids and bronchodilators. Within this group,…
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IL-20 Signaling in Activated Human Neutrophils Inhibits Neutrophil Migration and Function [INFECTIOUS DISEASE AND HOST RESPONSE]
Neutrophils possess multiple antimicrobial mechanisms that are critical for protection of the host against infection with extracellular microbes, such as the bacterial pathogen Staphylococcus aureus. Recruitment and activation of neutrophils at sites of infection are driven by cytokine and chemokine signals that directly target neutrophils via specific cell surface receptors. The IL-20 subfamily of cytokines has been reported to act at epithelial sites and contribute to psoriasis, wound healing, and anti-inflammatory effects during S. aureus infection. However, the ability of these cytokines to directly affect neutrophil function remains incompletely understood. In this article, we show that human neutrophils altered their expression of IL-20R chains upon migration and activation in vivo and in vitro. Such activation of neutrophils under conditions mimicking infection with S. aureus conferred responsiveness to IL-20 that manifested as modification of actin polymerization and inhibition of a broad range of actin-dependent functions, including phagocytosis, granule exocytosis, and migration. Consistent with the previously described homeostatic and anti-inflammatory properties of IL-20 on epithelial cells, the current study provides evidence that IL-20 directly targets and inhibits key inflammatory functions of neutrophils during infection with S. aureus.
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Paracrine IL-2 Is Required for Optimal Type 2 Effector Cytokine Production [IMMUNE REGULATION]
IL-2 is a pleiotropic cytokine that promotes the differentiation of Th cell subsets, including Th1, Th2, and Th9 cells, but it impairs the development of Th17 and T follicular helper cells. Although IL-2 is produced by all polarized Th subsets to some level, how it impacts cytokine production when effector T cells are restimulated is unknown. We show in this article that Golgi transport inhibitors (GTIs) blocked IL-9 production. Mechanistically, GTIs blocked secretion of IL-2 that normally feeds back in a paracrine manner to promote STAT5 activation and IL-9 production. IL-2 feedback had no effect on Th1- or Th17-signature cytokine production, but it promoted Th2- and Th9-associated cytokine expression. These data suggest that the use of GTIs results in an underestimation of the presence of type 2 cytokine–secreting cells and highlight IL-2 as a critical component in optimal cytokine production by Th2 and Th9 cells in vitro and in vivo.
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Kinase Activities of RIPK1 and RIPK3 Can Direct IFN-{beta} Synthesis Induced by Lipopolysaccharide [INNATE IMMUNITY AND INFLAMMATION]
The innate immune response is a central element of the initial defense against bacterial and viral pathogens. Macrophages are key innate immune cells that upon encountering pathogen-associated molecular patterns respond by producing cytokines, including IFN-β. In this study, we identify a novel role for RIPK1 and RIPK3, a pair of homologous serine/threonine kinases previously implicated in the regulation of necroptosis and pathologic tissue injury, in directing IFN-β production in macrophages. Using genetic and pharmacologic tools, we show that catalytic activity of RIPK1 directs IFN-β synthesis induced by LPS in mice. Additionally, we report that RIPK1 kinase–dependent IFN-β production may be elicited in an analogous fashion using LPS in bone marrow–derived macrophages upon inhibition of caspases. Notably, this regulation requires kinase activities of both RIPK1 and RIPK3, but not the necroptosis effector protein, MLKL. Mechanistically, we provide evidence that necrosome-like RIPK1 and RIPK3 aggregates facilitate canonical TRIF–dependent IFN-β production downstream of the LPS receptor TLR4. Intriguingly, we also show that RIPK1 and RIPK3 kinase–dependent synthesis of IFN-β is markedly induced by avirulent strains of Gram-negative bacteria, Yersinia and Klebsiella, and less so by their wild-type counterparts. Overall, these observations identify unexpected roles for RIPK1 and RIPK3 kinases in the production of IFN-β during the host inflammatory responses to bacterial infection and suggest that the axis in which these kinases operate may represent a target for bacterial virulence factors.
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Nature and Clonality of the Fluoresceinated Secondary Antibody in Luminex Multiplex Bead Assays Are Critical Factors for Reliable Monitoring of Serum HLA Antibody Levels in Patients for Donor Organ Selection, Desensitization Therapy, and Assessment of the Risk for Graft Loss [NOVEL IMMUNOLOGICAL METHODS]
Luminex multiplex immunoassays enable simultaneous monitoring of Abs against multiple Ags in autoimmune, inflammatory, and infectious diseases. The assays are used extensively to monitor anti-HLA Abs in transplant patients for donor organ selection, desensitization, and assessing the risk for graft rejection. To monitor IgG Abs, fluoresceinated IgG constant H chain–binding polyclonal F(ab')2 (IgHPolyFab) is used as the fluoresceinated secondary Ab (2nd-Ab), whereas IgG subclasses are monitored with Fc-specific monoclonal whole IgG (FcMonoIgG). The fluorescent signal from the 2nd-Ab is measured as mean florescence intensity (MFI). When IgHPolyFab is used, the signal is amplified as a result of the binding of multiple polyclonal Fabs to the C region of primary IgH. The reliability of such amplification for Ab measurements was not validated, nor were MFIs compared with 1:1 binding of FcMonoIgG to primary Abs. Comparing the MFIs of anti-HLA Abs obtained with IgHPolyFab and FcMonoIgG against normal human sera, IVIg, and allograft recipients' sera, it was observed that the number of HLA-Abs was notably higher with IgHPolyFab than with FcMonoIgG. The MFIs of anti-HLA Abs also remained higher with IgHPolyFab in the normal sera and in IVIg, but the reverse was true when the autologous and allogeneic IgG concentrations were augmented in allograft recipients. Indeed, MFIs of the de novo allo-HLA Abs were markedly higher with FcMonoIgG than with IgHPolyFab. Serum titration established the superiority of FcMonoIgG for monitoring MFIs of de novo allo-HLA Abs in allograft recipients. Avoiding false amplifications of the number and MFIs of anti-HLA IgG with FcMonoIgG may minimize immunosuppressive therapies, maximize the number of donors for patients waiting for allografts, and enable better prediction of graft rejection.
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Egr2 and 3 Inhibit T-bet-Mediated IFN-{gamma} Production in T Cells [INFECTIOUS DISEASE AND HOST RESPONSE]
T-bet is important for differentiation of cytotoxic CD8 and Th1 CD4 T cells. We have discovered that Egr2 and 3 are potent inhibitors of T-bet function in CD4 and CD8 effector T cells. Egr2 and 3 were essential to suppress Th1 differentiation in Th2 and Th17 conditions in vitro and also to control IFN-–producing CD4 and CD8 T cells in response to virus infection. Together with Egr2 and 3, T-bet is induced in naive T cells by Ag stimulation, but Egr2 and 3 expression was inhibited by Th1–inducing cytokines. We found that Egr2 and 3 physically interact with the T-box domain of T-bet, blocking T-bet DNA binding and inhibiting T-bet–mediated production of IFN-. Thus, Egr2 and 3 are antagonists of T-bet function in effector T cells and are important for the control of inflammatory responses of T cells.
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Novel Molecular Mechanism of Regulation of CD40 Ligand by the Transcription Factor GLI2 [MOLECULAR AND STRUCTURAL IMMUNOLOGY]
The interaction between tumor cells and their surrounding microenvironment is essential for the growth and persistence of cancer cells. This interaction is mediated, in part, by cytokines. Although the role of cytokines in normal and malignant cell biology is well established, many of the molecular mechanisms regulating their expression remain elusive. In this article, we provide evidence of a novel pathway controlling the transcriptional activation of CD40L in bone marrow–derived stromal cells. Using a PCR-based screening of cytokines known to play a role in the biology of bone marrow malignancies, we identified CD40L as a novel GLI2 target gene in stromal cells. CD40L plays an important role in malignant B cell biology, and we found increased Erk phosphorylation and cell growth in malignant B cells cocultured with CD40L-expressing stromal cells. Further analysis indicated that GLI2 overexpression induced increased CD40L expression, and, conversely, GLI2 knockdown reduced CD40L expression. Using luciferase and chromatin immunoprecipitation assays, we demonstrate that GLI2 directly binds and regulates the activity of the CD40L promoter. We found that the CCR3–PI3K–AKT signaling modulates the GLI2–CD40L axis, and GLI2 is required for CCR3–PI3K–AKT-mediated regulation of the CD40L promoter. Finally, coculture of malignant B cells with cells stably expressing human CD40L results in increased Erk phosphorylation and increased malignant B cell growth, indicating that CD40L in the tumor microenvironment promotes malignant B cell activation. Therefore, our studies identify a novel molecular mechanism of regulation of CD40L by the transcription factor GLI2 in the tumor microenvironment downstream of CCR3 signaling.
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Characterization of the Micro-Environment of the Testis that Shapes the Phenotype and Function of Testicular Macrophages [IMMUNE REGULATION]
Macrophages are important in the activation of innate immune responses and in a tissue-specific manner in the maintenance of organ homeostasis. Testicular macrophages (TM), which reside in the testicular interstitial space, comprise the largest leukocyte population in the testes and are assumed to play a relevant function in maintaining testicular immune privilege. Numerous studies have indicated that the interstitial fluid (IF) surrounding the TM has immunosuppressive properties, which may influence the phenotype of TM. However, the identity of the immunosuppressive molecules present in the IF is poorly characterized. We show that the rat testicular IF shifted GM-CSF–induced M1 toward the M2 macrophage phenotype. IF-polarized M2 macrophages mimic the properties of TM, such as increased expression of CD163, high secretion of IL-10, and low secretion of TNF-α. In addition, IF-polarized macrophages display immunoregulatory functions by inducing expansion of immunosuppressive regulatory T cells. We further found that corticosterone was the principal immunosuppressive molecule present in the IF and that the glucocorticoid receptor is needed for induction of the testis-specific phenotype of TM. In addition, TM locally produce small amounts of corticosterone, which suppresses the basal expression of inflammatory genes as a means to render TM refractory to inflammatory stimuli. Taken together, these results suggest that the corticosterone present in the testicular environment shapes the immunosuppressive function and phenotype of TM and that this steroid may play an important role in the establishment and sustenance of the immune privilege of the testis.
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Concomitant Disruption of CD4 and CD8 Genes Facilitates the Development of Double Negative {alpha}{beta} TCR+ Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen [INFECTIOUS DISEASE AND HOST RESPONSE]
Mature peripheral double negative T (DNT) cells expressing αβ TCR but lacking CD4/CD8 coreceptors play protective as well as pathogenic roles. To better understand their development and functioning in vivo, we concomitantly inactivated CD4 and CD8 genes in mice with intact MHC class I and class II molecules with the hypothesis that this would enable the development of DNT cells. We also envisaged that these DNT cells could be activated by bacterial superantigens in vivo as activation of T cells by superantigens does not require CD4 and CD8 coreceptors. Because HLA class II molecules present superantigens more efficiently than murine MHC class II molecules, CD4 CD8 double knockout (DKO) mice transgenically expressing HLA-DR3 or HLA-DQ8 molecules were generated. Although thymic cellularity was comparable between wild type (WT) and DKO mice, CD3+ αβ TCR+ thymocytes were significantly reduced in DKO mice, implying defects in thymic-positive selection. Splenic CD3+ αβ TCR+ cells and Foxp3+ T regulatory cells were present in DKO mice but significantly reduced. However, the in vivo inflammatory responses and immunopathology elicited by acute challenge with the staphylococcal superantigen enterotoxin B were comparable between WT and DKO mice. Choric exposure to staphylococcal enterotoxin B precipitated a lupus-like inflammatory disease with characteristic lympho-monocytic infiltration in lungs, livers, and kidneys, along with production of anti-nuclear Abs in DKO mice as in WT mice. Overall, our results suggest that DNT cells can develop efficiently in vivo and chronic exposure to bacterial superantigens may precipitate a lupus-like autoimmune disease through activation of DNT cells.
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Galectin-3: A Positive Regulator of Leukocyte Recruitment in the Inflamed Microcirculation [INNATE IMMUNITY AND INFLAMMATION]
In vivo and ex vivo imaging were used to investigate the function of galectin-3 (Gal-3) during the process of leukocyte recruitment to the inflamed microcirculation. The cremasteric microcirculation of wild-type (C57BL/6), Gal-3–/–, and CX3CR1gfp/+ mice were assessed by intravital microscopy after PBS, IL-1β, TNF-α, or recombinant Gal-3 treatment. These cellular responses were investigated further using flow-chamber assays, confocal microscopy, flow cytometry, PCR analysis, and proteome array. We show that mechanisms mediating leukocyte slow rolling and emigration are impaired in Gal-3–/– mice, which could be because of impaired expression of cell adhesion molecules and an altered cell surface glycoproteome. Local (intrascrotal) administration of recombinant Gal-3 to wild-type mice resulted in a dose-dependent reduction in rolling velocity associated with increased numbers of adherent and emigrated leukocytes, ~50% of which were Ly6G+ neutrophils. Intrascrotal administration of Gal-3 to CX3CR1gfp/+ mice confirmed that approximately equal numbers of monocytes are also recruited in response to this lectin. Exogenous Gal-3 treatment was accompanied by increased proinflammatory cytokines and chemokines within the local tissue. In conclusion, this study unveils novel biology for both exogenous and endogenous Gal-3 in promoting leukocyte recruitment during acute inflammation.
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Murinization and H Chain Isotype Matching of the Anti-GITR Antibody DTA-1 Reduces Immunogenicity-Mediated Anaphylaxis in C57BL/6 Mice [TUMOR IMMUNOLOGY]
Recent advances in immuno-oncology have shown that the immune system can be activated to induce long-term, durable antitumor responses. For immuno-oncology drug development, immune activation is often explored using rat Abs in immunocompetent mouse models. Although these models can be used to show efficacy, antidrug immune responses to experimental protein-based therapeutics can arise. Immunogenicity of surrogate Abs may therefore represent an important obstacle to the evaluation of the antitumor efficacy of immunomodulator Abs in syngeneic models. A recent publication has shown that anti-glucocorticoid–induced TNFR family–related protein agonistic Ab DTA-1 (rat or murinized IgG2a) can induce the development of anaphylaxis in C57BL/6 mice upon repeated i.p. dosing because of an anti-idiotypic anti-drug Ab immune response. This study was undertaken to address the impact of the immunogenicity derived from the Fc and variable domains. To this end, chimerized (rat V domains/mouse constant regions) and murinized (95% mouse sequence) DTA-1–based surrogate Abs with a murine IgG2c H chain isotype were created. Chimerization and murinization of DTA-1 did not affect receptor binding and glucocorticoid-induced TNFR family–related protein–induced T cell agonistic properties. Similar in vivo antitumor efficacy and intratumoral CD8+/regulatory T cells were also observed. Finally, treatment of C57BL/6 mice with the chimerized and murinized DTA-1 Abs on a C57BL/6-matched IgG2c isotype resulted in reduced development and severity of anaphylaxis as measured by decline of body temperature, behavioral effects, serum IL-4, IgE, and anti-drug Ab levels. These results suggest that careful murinization and selection of a strain-matched H chain isotype are critical to generate ideal surrogate Abs for testing immuno-oncology mechanisms in vivo.
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Definition of the Nature and Hapten Threshold of the {beta}-Lactam Antigen Required for T Cell Activation In Vitro and in Patients [ANTIGEN RECOGNITION AND RESPONSES]
Covalent modification of protein by drugs may disrupt self-tolerance, leading to lymphocyte activation. Until now, determination of the threshold required for this process has not been possible. Therefore, we performed quantitative mass spectrometric analyses to define the epitopes formed in tolerant and hypersensitive patients taking the β-lactam antibiotic piperacillin and the threshold required for T cell activation. A hydrolyzed piperacillin hapten was detected on four lysine residues of human serum albumin (HSA) isolated from tolerant patients. The level of modified Lys541 ranged from 2.6 to 4.8%. Analysis of plasma from hypersensitive patients revealed the same pattern and levels of modification 1–10 d after the commencement of therapy. Piperacillin-responsive skin-homing CD4+ clones expressing an array of Vβ receptors were activated in a dose-, time-, and processing-dependent manner; analysis of incubation medium revealed that 2.6% of Lys541 in HSA was modified when T cells were activated. Piperacillin–HSA conjugates that had levels and epitopes identical to those detected in patients were shown to selectively stimulate additional CD4+ clones, which expressed a more restricted Vβ repertoire. To conclude, the levels of piperacillin–HSA modification that activated T cells are equivalent to the ones formed in hypersensitive and tolerant patients, which indicates that threshold levels of drug Ag are formed in all patients. Thus, the propensity to develop hypersensitivity is dependent on other factors, such as the presence of T cells within an individual's repertoire that can be activated with the β-lactam hapten and/or an imbalance in immune regulation.
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Measuring cortical motor hemodynamics during assisted stepping – An fNIRS feasibility study of using a walker
Publication date: July 2017
Source:Gait & Posture, Volume 56
Author(s): Andrea Cristina de Lima-Pardini, Guilherme A. Zimeo Morais, Joana Bisol Balardin, Daniel Boari Coelho, Nametala Maia Azzi, Luis Augusto Teixeira, João Ricardo Sato
Walkers are commonly prescribed worldwide to individuals unable to walk independently. Walker usage leads to improved postural control and voluntary movement during step. In the present study, we aimed to provide a concept-proof on the feasibility of an event-related protocol integrating the analyses of biomechanical variables of step initiation and functional near-infrared spectroscopy (fNIRS) to measure activation of the supplementary motor area (SMA) while using a walker. Healthy young participants were tested while stepping with versus without the use of the walker. Behavioral analysis showed that anticipatory postural adjustments (APA) decreased when supporting the body weight on the walker. Delta (without–with) of activation magnitude of the muscle tibialis anterior was positively correlated to the delta of deoxyhemoglobin concentration changes in the SMA. The novelty of this study is the development of a protocol to assess brain function together with biomechanical analysis during the use of a walker. The method sheds light to the potential utility of combining fNIRS and biomechanical assessment during assistive step initiation, which can represent a new opportunity to study populations with mobility deficits.
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Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma
Asthma is a common chronic inflammatory disease of the airways that affects an estimated 315 million persons worldwide. Approximately 5 to 10% of persons with asthma have a severe form of disease that is usually managed with high-dose inhaled glucocorticoids and bronchodilators. Within this group,…
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The influence of shoe aging on children running biomechanics
Publication date: July 2017
Source:Gait & Posture, Volume 56
Author(s): Alexis Herbaut, Pascale Chavet, Maxime Roux, Nils Guéguen, Franck Barbier, Emilie Simoneau-Buessinger
Athletic children are prone to overuse injuries, especially at the heel and knee. Since footwear is an extrinsic factor of lower limb injury risk, the aim of this study was to assess the influence of shoe aging on children running biomechanics. Fourteen children active in sports participated in a laboratory biomechanical evaluation. A new pair of shoes was provided to each participant at an inclusion visit. Four months later, the participants performed a running task and their kinematics and kinetics were assessed both with their used shoes and with a new pair of shoes identical to the first. Furthermore, mechanical cushioning properties of shoes were evaluated before and after in-vivo aging. After 4months of use, the sole stiffness increased by 16% and the energy loss capacity decreased by 18% (p<0.001). No ankle or knee kinematic adjustment was found at foot strike in used shoes but changes were observed later during stance. Running with used shoes produced a higher loading rate of the vertical ground reaction force (+23%, p=0.016), suggesting higher compressive forces under the heel and placing children at risk to experience impact-related injuries. Nevertheless, the decreased peak ankle and knee power absorption in used shoes (−11%, p=0.010 and −12%, p=0.029, respectively) suggests a lower ankle and knee joints loading during the absorption phase that may be beneficial regarding stretch-related injuries.
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The influence of continuous versus interval walking exercise on knee joint loading and pain in patients with knee osteoarthritis
Publication date: July 2017
Source:Gait & Posture, Volume 56
Author(s): Shawn Farrokhi, Prakash Jayabalan, Jonathan A. Gustafson, Brian A. Klatt, Gwendolyn A. Sowa, Sara R. Piva
ObjectiveTo evaluate whether knee contact force and knee pain are different between continuous and interval walking exercise in patients with knee osteoarthritis (OA).MethodsTwenty seven patients with unilateral symptomatic knee OA completed two separate walking exercise sessions on a treadmill at 1.3m/s on two different days: 1) a continuous 45min walking exercise session, and 2) three 15min bouts of walking exercise separated by 1h rest periods for a total of 45min of exercise in an interval format. Estimated knee contact forces using the OpenSim software and knee pain were evaluated at baseline (1st minute of walking) and after every 15min between the continuous and interval walking conditions.ResultsA significant increase from baseline was observed in peak knee contact force during the weight-acceptance phase of gait after 30 and 45min of walking, irrespective of the walking exercise condition. Additionally, whereas continuous walking resulted in an increase in knee pain, interval walking did not lead to increased knee pain.ConclusionWalking exercise durations of 30min or greater may lead to undesirable knee joint loading in patients with knee OA, while performing the same volume of exercise in multiple bouts as opposed to one continuous bout may be beneficial for limiting knee pain.
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