Reference intervals of thyroid hormones in Khartoum, Sudan

This study aimed to establish the reference intervals (RIs) of thyroid function test among the adult Sudanese population in Khartoum, Sudan. A multi-stage survey stratified sampling method was used. Total trii...

https://ift.tt/2ISr7Jw

Factors associated with rapidly repeated acute poisoning by substances of abuse: a prospective observational cohort study

We have previously found that 9% of patients treated for acute poisoning by substances of abuse in a primary care emergency outpatient setting presented with a new poisoning within a week. We now identify fact...

https://ift.tt/2OmPHId

Assessment of drug related problems among type 2 diabetes mellitus patients with hypertension in Hiwot Fana Specialized University Hospital, Harar, Eastern Ethiopia

This study was conducted to assess magnitude and pattern of drug related problems among patients with type 2 diabetes mellitus (T2DM) and hypertension.

https://ift.tt/2ISr7t0

Oxidant–antioxidant status and assessment of cardiovascular morbidity in Pan Masala containing Tobacco users: a cross-sectional study

Pan Masala containing Tobacco (PMT) use contributes significantly to the overall world tobacco burden especially in south Asian country like Nepal. Oxidative stress caused by it may leads to cardiovascular dis...

https://ift.tt/2OnecoP

Sleeping beauty syndrome presenting with insomnia

A young man previously diagnosed with Kleine-Levin syndrome (KLS) presented with abnormal behaviour over the last 8 days. This included decreased sleeping hours and appetite, hypersexuality, aggressiveness and visual hallucinations. All blood tests and investigations in the emergency department yielded normal results. A preliminary diagnosis of a KLS episode with psychosis was made and the patient was started on a regimen of aripiprazole 10 mg once daily along with lorazepam 2 mg intravenously in two divided doses in the event of agitation or insomnia. On discharge 5 days later, the patient had returned to his premorbid level of functioning and was willing to follow up in the neurology clinic. He was discharged on aripiprazole 10 mg once daily and lorazepam 2 mg two times daily as needed for 2 weeks to help with his agitation and insomnia, as well as lithium carbonate 400 mg at night.

https://ift.tt/2RMAyOr

Takotsubo syndrome with severe bradycardia initiated by seizure: Is the implantation of a permanent pacemaker necessary?

Although arrhythmias are frequent in patients with Takotsubo syndrome (TTS), data on sick sinus syndrome remain elusive. Here, we report a case of TTS initiated by a seizure as a physical trigger that led to sinus arrest. The patient presented with cardiogenic shock and bradycardia which required intensive cardiovascular care. However, in the subacute phase of TTS, the sinus function recovered significantly, and pacemaker implantation was deferred.

https://ift.tt/2Eg1l2Y

Living donor renal transplant in a patient with end-stage renal disease due to Hermansky-Pudlak syndrome

Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder characterised by oculocutaneous albinism, bleeding diathesis and end-stage renal disease (ESRD), due to interstitial deposition of ceroid lipofuscin. Renal transplantation is potentially a definitive treatment option for patients with ESRD due to HPS. Herein, we describe the case of a 55-year-old male patient with HPS that successfully underwent a living donor kidney transplant. We also emphasise the importance of multidisciplinary input during the preoperative, perioperative and postoperative phases in this high-risk clinical scenario.

https://ift.tt/2RLPNav

Living donor liver transplantation and situs inversus totalis: cutting the Gordian knot

Liver transplantation for biliary atresia splenic malformation syndrome associated with situs inversus totalis is a challenging task due to the complexity of associated malformations and the technical proficiency required to overcome them. We present the case of a 6-month-old infant who underwent liver transplantation for biliary atresia. A reduced left lateral segment liver graft from a live donor (his mother) was implanted. The postoperative period was uneventful, and the child remained well on follow-up. Thus, such rare congenital anomalies no longer prove to be a deterrent for successful liver transplantation.

https://ift.tt/2EfGpt2

Unusual case of unilateral conductive hearing loss: chronic lymphocytic leukaemia

This presentation reports a novel case of chronic lymphocytic leukaemia (CLL), presenting with an early cutaneous lesion within the external auditory canal, in a patient being assessed for conductive hearing loss. It has previously been reported that infiltrative CLL can involve the head and neck; however, isolated external ear canal involvement is rare. Given that the incidence of CLL in Australia is rising, this case highlights the importance of considering CLL as a differential diagnosis for presentations of unilateral conductive hearing loss.

https://ift.tt/2RMAuyb

Corneal ulcer as the presenting feature of type 2 diabetes mellitus

A 60-year-old woman, with no significant medical or ophthalmic history, presented with a unilateral large corneal ulcer and hypopyon. Despite a severely injected conjunctiva and large corneal epithelial defect, the patient denied any discomfort in the eye. The ulcer was extremely slow to heal requiring prolonged treatment with topical and systemic broad-spectrum antibiotics. Due to the corneal opacification, fundal examination was not possible. Subsequent examination of the fellow eye revealed an appearance consistent with proliferative diabetic retinopathy. She was given treatment with panretinal laser photocoagulation. There was no history of diabetes and the patient denied experiencing any of the classical symptoms of hyperglycaemia. With blood tests revealing a raised plasma glucose and Haemoglobin A1c (HbA1c), a new diagnosis of diabetes mellitus was made. With the commencement of treatment for diabetes, there were signs of improvement in the corneal appearance.

https://ift.tt/2EjtOVF

Mesenteric panniculitis: diagnostic precision

A previously healthy 74-year-old woman was admitted with vespertine fever, tremors, shivers and loss of appetite within the previous month. Blood tests revealed an elevated C reactive protein serum level. Serologies for infection were negative. Blood cultures grew no organisms. Colonoscopy revealed normal findings. CT showed typical findings of mesenteric panniculitis with infiltration of mesenteric fat that was circumscribed by hyperattenuating capsule and contained enlarged homogenous lymph nodes. The histopathological analysis from mesenterium revealed non-specific signs of chronic inflammation. On institution of prednisolone, the clinical symptoms subsided, and we replaced it with azathioprine after 1 month. After 12 months of therapy, the patient remained asymptomatic, normalised the serological inflammatory markers and repeat CT revealed normal mesenteric fat.

https://ift.tt/2RMArT1

Bilateral congenital eventration of diaphragm: keep in mind, the other side

Eventration of diaphragm is an uncommon disorder in which diaphragmatic muscle is replaced by fibroelastic tissue, either partially or completely. Bilateral eventration is even rarer. We present a case of bilateral eventration of diaphragm in newborn with a fibroelastic sac on left side and diaphragmatic eventration with good muscular lips on right side. The right-sided diaphragmatic eventration was not evident initially, but manifested after surgical repair of the left-sided eventration.

https://ift.tt/2EqQWBY

Cerebrospinal fluid hydrocele caused by scrotal migration of a ventriculoperitoneal shunt

A 6-month-old boy presented with painless right hemiscrotal swelling. The scrotal ultrasound revealed a cerebrospinal fluid hydrocele caused by the migration of a ventriculoperitoneal shunt (VPS) catheter tip into the right hemiscrotum and associated undescended left testis. Earlier, he underwent a VPS placement for hydrocephalus secondary to neonatal bacterial meningitis and ventriculitis. The patient was treated with bilateral herniotomy, left-sided orchidopexy and repositioning of VPS into the peritoneal cavity.

https://ift.tt/2RFDjBn

Methicillin-sensible Staphylococcus aureus causing endocarditis, with cerebral and orthopaedic complications, in a 17-month-old child with no risk factor

We report a case of Staphylococcus aureus endocarditis, with large vegetation, in a 17-month-old male infant, complicated with meningitis, ischaemic strokes and osteoarthritis leading to haemorrhagic stroke by aneurysm rupture. He did not present any risk factor for endocarditis. The final course was favourable through, after valve replacement. The strain was sensible to methicillin and belongs to complex clonal 398, with accessory gene regulator I. We did not found immunodeficiency.

https://ift.tt/2Eg0Cig

Unilateral localized extraocular muscle metastasis by lobular breast carcinoma

Here is a case of an isolated orbital metastasis in a previously diagnosed metastatic breast cancer of a 46-year-old woman presenting diplopia and pain in her left eye. The magnetic resonance showed a suspected metastatic localisation in the upper left oblique muscle, which was confirmed by the fine-needle aspiration biopsy. The systemic therapy with liposomal doxorubicin as well as local stereotactic radiotherapy showed a gradual improvement of the local symptoms and signs.

https://ift.tt/2RMAn5J

A snotty nose: more than just a cold

Description 

A healthy 3-year-old girl presented with a 5-day history of right-sided cheek and eye swelling and pain, associated with right-sided green nasal discharge. Examination revealed diffuse erythematous swelling around the right cheek, jawline and eye. Oral antibiotics for suspected periorbital cellulitis were ineffective. Blood inflammatory markers and ultrasound of her neck and parotid glands were normal. She was discharged as having viral parotitis. Antibiotics and nasal drops were later restarted for clinical sinusitis; however, she showed no improvement, now having 3 weeks of right-sided facial swelling with thick green and intermittently bloody nasal discharge. Further history revealed possible squint, mastication pain and breathing difficulty through the right nostril.

Cranial imaging (figure 1) demonstrated a large central but predominantly right-sided nasopharyngeal tumour, extending into the ethmoid sinuses and orbits (with medial recti distortion), infratemporal fossa and pterygoid muscles and anterior and middle cranial fossae. There was...

https://ift.tt/2Eg0y20

Disseminated nocardiosis with infective endocarditis of a transplanted heart

Nocardiosis is caused by various species of Nocardia and typically occurs as an opportunistic infection. It frequently disseminates, most often involving the lungs, subcutaneous tissues and central nervous system. It has rarely been reported to affect native heart valves. We report the case of a 64-year-old man with disseminated nocardiosis involving the brain, lungs, muscle and tricuspid valve of a transplanted heart. Following antimicrobial therapy, the patient improved clinically and there was no evidence of residual infection on follow-up imaging. This case highlights the presentation of nocardiosis, current therapeutic guidelines and the question of prophylaxis against Nocardia in immunocompromised patients.

https://ift.tt/2RMAjTx

Toxic epidermal necrolysis: the red eye and red herrings in casualty

A 38-year-old woman presented to casualty with bilateral red eyes associated with a recent upper respiratory tract infection. This was initially diagnosed as conjunctivitis, however systemic review revealed an erythematous facial and skin rash, mildly swollen lips and mild swallowing difficulties. The patient was referred for an urgent medical assessment, by which time she was found to have erythema affecting 54% of her body surface area and diagnosed with suspected toxic epidermal necrolysis (TEN). She rapidly deteriorated over 24 hours with a spreading blistering skin rash and airway compromise requiring urgent intubation and admission to the intensive treatment unit (ITU). Subsequent skin biopsies confirmed the diagnosis of TEN, attributed to recent use of ibuprofen. Treatment included broad-spectrum antibiotics and high-dose corticosteroids. The patient had a prolonged hospital stay and developed severe scarring of the ocular surface. She was discharged home and remains under continuing outpatient follow-up with ophthalmology and dermatology teams.

https://ift.tt/2Eg0tLK

Neonate with urinary ascites but no hydronephrosis: unusual presentation of posterior urethral valves

Posterior urethral valves (PUV) are an important cause of paediatric obstructive uropathy. PUV are usually diagnosed by prenatal ultrasonography (US) revealing hydronephrosis and bladder distention. We describe a 17-day-old male infant with abdominal distention who had no hydronephrosis on prenatal US. Laboratory investigations showed serum creatinine of 12 mg/dL, hyperkalaemia and metabolic acidosis. Abdominal US showed large amount of ascites, normal-sized kidneys without hydronephrosis and incompletely distended bladder. Paracentesis revealed clear, yellow ascitic fluid with creatinine level of 27 mg/dL compatible with urinary ascites. Voiding cystourethrogram (VCUG) demonstrated PUV with a dilated posterior urethra, grade 5 right vesicoureteral reflux and a ruptured kidney fornix with peritoneal extravasation of contrast. Foley decompression resulted in normalisation of creatinine within 72 hours. Transurethral resection of PUV was performed, and a repeat VCUG showed recovery of forniceal rupture. This case illustrates an unusual presentation of a potentially life-threatening but treatable cause of urinary tract obstruction.

https://ift.tt/2RMAgqP

Acute pancreatitis-induced takotsubo cardiomyopathy and cardiogenic shock treated with a percutaneous left ventricular assist device

A 63-year-old man was admitted for severe acute pancreatitis. On day 3 of hospitalisation, he developed shortness of breath and acute pulmonary oedema. Echocardiogram revealed global hypokinesis with a left ventricular ejection fraction of 20%, and he was diagnosed with takotsubo cardiomyopathy. He developed cardiogenic shock which was treated successfully with a percutaneous left ventricular assist device. His left ventricular ejection fraction improved by hospital follow-up 3 weeks later.

https://ift.tt/2Eg0q2w

Secondary bacterial peritonitis and pelvic abscess due to Clostridium difficile

A 70-year-old man with a history of hepatic cirrhosis presented with abdominal discomfort and distention. Physical examination revealed abdominal distention, positive fluid wave and abdominal tenderness. Due to concerns for spontaneous bacterial peritonitis (SBP), paracentesis was performed. Fluid analysis revealed 5371 total nucleated cells with 48% neutrophils. Ceftriaxone was then initiated for the treatment of SBP. Bacterial cultures of the fluid, however, grew Clostridium difficile. Therefore, metronidazole was added. An abdominal ultrasound revealed a pelvic fluid collection that was suspicious for an abscess on an abdominal CT scan. The patient underwent CT-guided drain placement into the pelvic fluid collection. The fluid aspirate was consistent with an abscess. However, cultures were negative in the setting of ongoing antibiotic therapy. The patient was treated with a 10-day course of ceftriaxone and metronidazole and was discharged home with outpatient follow-up.

https://ift.tt/2RMAeiH

Stage III Kienböcks disease treated with hyperbaric oxygen: the role of an unusual approach to a rare condition

Kienböck's disease is a rare condition characterised by avascular necrosis of the lunate bone. Its natural history and aetiopathogenesis have not yet been clarified, nor are its triggering factors identified. We present a case of a 17-year-old male gymnast, without relevant medical/family history, with stage IIIA Kienböck's disease diagnosed in 2016. Initially, submitted to conservative treatment that proved to be insufficient. Consequently, surgical treatment was proposed, but refused. The patient instead underwent experimental treatment with hyperbaric oxygen (120 sessions, 100% oxygen at 2.5 atm, for 70 min periods, once daily, five times per week). In April 2018, a favourable clinical and radiological evolution was observed, with an improvement in the patterns of pain, motion and strength and an almost complete involution of the process of aseptic necrosis of the semilunar. To the best of our knowledge, this is the first report of Kienböck's disease treated with hyperbaric oxygen.

https://ift.tt/2Eg0n6Q

Case of newly diagnosed bilateral anorchia in a 42-year-old male patient

A 42-year-old African man presented with hypogonadic phenotypical features, including gynoid body distribution, gynaecomastia, absent facial and truncal hair and micropenis. He denied ever experiencing development of male secondary sex characteristics. Endocrine testing revealed hypergonadotropic hypogonadism and undetectable AMH. Human chorionic gonadotropin (hCG) stimulation test failed to increase testosterone levels. Peripheral blood karyotype was 46, XY. Clinical examination and abdominal/pelvic/scrotal ultrasound and MRI failed to identify any testicular structures/remnants. Given the clinical course and the biochemical–radiological presentation, the diagnosis of bilateral anorchia was made (after more than four decades of its probable onset), and surgical exploration was decided against. The patient was subsequently started on monthly intramuscular testosterone experiencing progressive normal virilisation.

https://ift.tt/2RMA7DN

Early initiation of venovenous extracorporeal membrane oxygenation in a mechanically ventilated patient with severe acute respiratory distress syndrome

A 49-year-old man presented to the emergency department with acute-onset dyspnoea and hypoxaemia 1 day following nasal surgery for obstructive sleep apnoea. A chest X-ray showed diffuse bilateral pulmonary infiltrates. Supplemental 100% fractional inspired oxygen (FiO₂) via non-rebreather mask was delivered with resulting arterial oxygen tension:FiO₂ ratio of 67. Transthoracic echocardiogram demonstrated normal heart function. A clinical diagnosis of severe acute respiratory distress syndrome (ARDS) was promptly made. Based on patient preference to avoid intubation and following a multidisciplinary approach, we decided to initiate venovenous extracorporeal membrane oxygenation (VV-ECMO) as an alternative strategy to mechanical ventilation. Though he ultimately required brief mechanical ventilation during ECMO cannulation, the patient spent a total of 5 days on VV-ECMO and a total of 8 days in the intensive care unit. Six days after discharge, his pulmonary function test demonstrated no significant abnormalities. We present a rare case of early initiation of VV-ECMO in a patient with severe ARDS that served as a bridge to recovery.

https://ift.tt/2Eg0T4M

New Morbidity and Discharge Disposition of Pediatric Acute Respiratory Distress Syndrome Survivors*

Objectives: Much of the research related to pediatric acute respiratory distress syndrome has focused on inhospital mortality and interventions affecting this outcome. Limited data exist on survivors' morbidity, hospital disposition, and 1-year survival. The aim of this study was to determine new morbidity rate, discharge disposition, and 1-year mortality for survivors of pediatric acute respiratory distress syndrome. Design: Secondary analysis of prospective cohort study. Setting: Quaternary children's hospital. Patients: Three-hundred sixteen mechanically ventilated children with pediatric acute respiratory distress syndrome (Berlin and Pediatric Acute Lung Injury Consensus Conference criteria) between July 2011 and December 2014. Interventions: None. Measurements and Main Results: We performed secondary analysis of a prospectively recruited cohort of 316 mechanically ventilated children with pediatric acute respiratory distress syndrome between July 2011, and December 2014. Preillness and hospital discharge Functional Status Scale score were determined via chart review, and factors associated with new morbidity, defined as an increase of Functional Status Scale score of 3 or more, were analyzed. Demographic variables, pediatric acute respiratory distress syndrome characteristics, and ventilator management were tested for association with development of new morbidity, discharge disposition, and 1-year mortality. Inhospital mortality of pediatric acute respiratory distress syndrome was 13.3% (42/316). Of 274 survivors to hospital discharge, new morbidity was seen in 63 patients (23%). Discharge to rehabilitation rate was 24.5% (67/274) and associated with development of new morbidity. One- and 3-year mortality of survivors was 5.5% (15 deaths) and 8% (22 deaths) and was associated with baseline Functional Status Scale, immunocompromised status, Pediatric Risk of Mortality III, and organ failures at pediatric acute respiratory distress syndrome onset, but not with pediatric acute respiratory distress syndrome severity. Conclusions: New morbidity was common after pediatric acute respiratory distress syndrome and appears to be intermediate phenotype between survival without morbidity and death, making it a useful metric in future interventional and outcome studies in pediatric acute respiratory distress syndrome.

https://ift.tt/2QLJRge

Systemic High-Mobility Group Box-1: A Novel Predictive Biomarker for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage*

Objectives: To investigate the release of proinflammatory damage-associated molecular pattern molecule "high-mobility group box-1" in the serum of patients after aneurysmal subarachnoid hemorrhage and its association with cerebral vasospasm. Design: Retrospective observational study. Setting: University hospital. Patients: Aneurysmal subarachnoid hemorrhage patients admitted within 24 hours of ictus. Interventions: Standard subarachnoid hemorrhage treatment after clipping or coiling of aneurysm. Measurements and Main Results: We enrolled 53 aneurysmal subarachnoid hemorrhage patients from which peripheral venous blood was withdrawn on days 1, 3, 5, 7, 9, 11, and 13 and once from the controls to obtain the serum. Serum high-mobility group box-1 concentration was quantified by enzyme-linked immunosorbent assay. Serum interleukin-6 and peripheral blood leukocytes were also determined over the first 2 weeks after subarachnoid hemorrhage. Patients' data were recorded prospectively. Serum high-mobility group box-1 was significantly elevated in subarachnoid hemorrhage patients from day 1 to day 13 when compared with nonsubarachnoid hemorrhage patients (p

https://ift.tt/2A7EJxO

Changes in Temperature Management of Cardiac Arrest Patients Following Publication of the Target Temperature Management Trial*

Objectives: To evaluate knowledge translation after publication of the target temperature management 33°C versus 36°C after out-of-hospital cardiac arrest trial and associated patient outcomes. Our primary hypothesis was that target temperature management at 36°C was rapidly adopted in Australian and New Zealand ICUs. Secondary hypotheses were that temporal reductions in mortality would be seen and would have accelerated after publication of the target temperature management trial. Design: Retrospective cohort study (January 2005 to December 2016). Setting: The Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient database containing greater than 2 million admission episodes from 186 Australian and New Zealand ICUs. Patients: Sixteen-thousand two-hundred fifty-two adults from 140 hospitals admitted to ICU after out-of-hospital cardiac arrest. Interventions: The primary exposure of interest was admission before versus after publication of the target temperature management trial. Measurements and Main Results: The primary outcome variable to evaluate changes in temperature management was lowest temperature in the first 24 hours in ICU. The primary clinical outcome variable of interest was inhospital mortality. Secondary outcomes included proportion of patients with fever in the first 24 hours in ICU. Mean ± SD lowest temperature in the first 24 hours in ICU in pre- and posttarget temperature management trial patients was 33.80 ± 1.71°C and 34.70 ± 1.39°C, respectively (absolute difference, 0.98°C [99% CI, 0.89–1.06°C]). Inhospital mortality rate decreased by 1.3 (99% CI, –1.8 to –0.9) percentage points per year from January 2005 until December 2013 and increased by 0.6 (99% CI, –1.4 to 2.6) percentage points per year from January 2014 until December 2016 (change in slope 1.9 percentage points per year [99% CI, –0.6 to 4.4]). Fever occurred in 568 (12.8%) of 4,450 pretarget temperature management trial patients and 853 (16.5%) of 5,184 posttarget temperature management trial patients (odds ratio, 1.35 [99% CI, 1.16–1.57]). Conclusions: The average lowest temperature of postcardiac arrest patients in the first 24 hours in ICU rose after publication of the target temperature management trial. This change was associated with an increased frequency of fever not seen in the target temperature management trial.

https://ift.tt/2QPPj1X

Handovers Among Staff Intensivists: A Study of Information Loss and Clinical Accuracy to Anticipate Events*

Objectives: Handovers are associated with medical errors, and our primary objective is to identify missed diagnosis and goals immediately after a shift handover. Our secondary objective is to assess clinicians' diagnostic accuracy in anticipating clinical events during the night shift. Design: Single-center prospective observational cohort study. Setting: Thirty-bed tertiary ICU in Sao Paulo, Brazil. Patients: Three-hundred fifty-two patient encounters over 44 day-to-night handovers. Interventions: None. Measurements and Main Results: We used a multimethods approach to measure transmission of information among staff physicians on diagnoses and goals for the night shift. We surveyed clinicians immediately after a handover and identified clinical events through chart abstractions and interviews with clinicians the next morning. Nighttime clinicians correctly identified 454 of 857 diagnoses (53%; 95% CI 50–56) and 123 of 304 goals (40%; 95% CI, 35–46). Daytime clinicians were more sensitive (65% vs 46%; p

https://ift.tt/2A85ySk

Focusing on Risk Factors of Cardiac Arrest During Intubation in ICU Again

No abstract available

https://ift.tt/2A8So7J

Low Interleukin-7 Receptor Messenger RNA Expression Is Independently Associated With Day 28 Mortality in Septic Shock Patients*

Objectives: Septic shock is the primary cause of death in ICUs. A better comprehension of its pathophysiology, in particular, the immune alteration mechanisms, opened new therapeutic perspectives such as the recombinant interleukin-7. The use of biomarkers could improve the identification of eligible patients for this therapy. The soluble form of the interleukin-7 appears as a promising candidate in this regard since an association between its high plasmatic level and mortality in critically ill patients has been demonstrated. Because there are no data available on the transcriptional regulation of the interleukin-7 receptor in such patients, this study aimed to explore the expression level of different interleukin-7 receptor transcripts after septic shock and evaluate their association with mortality. Design: Retrospective discovery cohort (30 patients) and validation cohort (177 patients). Setting: Two French ICUs (discovery study) and six French ICUs (validation study). Patients: Adult septic shock patients. Interventions: None. Measurements and Main Results: The quantification of several interleukin-7 receptor transcripts using specific reverse transcription quantitative polymerase chain reaction designs allowed for global evaluation of interleukin-7 receptor gene expression in whole blood. In the discovery cohort, all interleukin-7 receptor transcripts studied were expressed at lower levels in septic shock patients than in healthy volunteers. Interleukin-7 receptor gene expression at day 3 after septic shock diagnosis was associated with day 28 mortality. Patients at a lower risk of death showed higher expression levels. These results were confirmed in the independent validation cohort. Interestingly, using a threshold obtained on the discovery cohort, we observed in the validation cohort a high negative predictive value for day 28 mortality for the transcript encoding the membrane form of interleukin-7 receptor (0.86; 95% CI, 0.79–0.93). Conclusions: Interleukin-7 receptor transcripts appear as biomarkers of impaired adaptive immune response in septic shock patients and as a promising tool for patient stratification in clinical trials evaluating immunoadjuvant therapies.

https://ift.tt/2QN6Do7

Inhaled Nitric Oxide for Pediatric Acute Respiratory Distress Syndrome: Another Brick in the Wall?*

No abstract available

https://ift.tt/2A7Wjlb

Effect of Thiamine Administration on Lactate Clearance and Mortality in Patients With Septic Shock*

Objectives: Mounting evidence has shown that critically ill patients are commonly thiamine deficient. We sought to test the hypothesis that critically ill patients with septic shock exposed to thiamine would demonstrate improved lactate clearance and more favorable clinical outcomes compared with those not receiving thiamine. Design: Retrospective, single-center, matched cohort study. Setting: Tertiary care academic medical center. Patients: Adult patients admitted with an International Classification of Diseases, 9th Edition, or International Classification of Diseases, 10th Edition, diagnosis code of septic shock to either the medicine or surgery ICU. Interventions: None. Measurements and Main Results: Patients who received IV thiamine supplementation within 24 hours of hospital admission were identified and compared with a matched cohort of patients not receiving thiamine. The primary objective was to determine if thiamine administration was associated with a reduced time to lactate clearance in septic shock. Secondary outcomes included 28-day mortality, acute kidney injury, and need for renal replacement therapy, and vasopressor and mechanical ventilation-free days. Two-thousand two-hundred seventy-two patients were screened, of whom 1,049 were eligible. The study consisted of 123 thiamine-treated patients matched with 246 patients who did not receive thiamine. Based on the Fine-Gray survival model, treatment with thiamine was associated with an improved likelihood of lactate clearance (subdistribution hazard ratio, 1.307; 95% CI, 1.002–1.704). Thiamine administration was also associated with a reduction in 28-day mortality (hazard ratio, 0.666; 95% CI, 0.490–0.905). There were no differences in any secondary outcomes. Conclusions: Thiamine administration within 24 hours of admission in patients presenting with septic shock was associated with improved lactate clearance and a reduction in 28-day mortality compared with matched controls.

https://ift.tt/2QLXfRS

Early Right Ventricular Systolic Dysfunction and Pulmonary Hypertension Are Associated With Worse Outcomes in Pediatric Acute Respiratory Distress Syndrome

Objectives: The prevalence and importance of early right ventricular dysfunction and pulmonary hypertension in pediatric acute respiratory distress syndrome are unknown. We aimed to describe the prevalence of right ventricular dysfunction and pulmonary hypertension within 24 hours of pediatric acute respiratory distress syndrome diagnosis and their associations with outcomes. Design: Retrospective, single-center cohort study. Setting: Tertiary care, university-affiliated PICU. Patients: Children who had echocardiograms performed within 24 hours of pediatric acute respiratory distress syndrome diagnosis. Interventions: None. Measurements and Main Results: Between July 1, 2012, and June 30, 2016, 103 children met inclusion criteria. Echocardiograms were analyzed using established indices of right ventricular and left ventricular systolic function and for evidence of pulmonary hypertension. Echocardiographic abnormalities were common: 26% had low right ventricular fractional area change, 65% had low tricuspid annular plane systolic excursion, 30% had low left ventricular fractional shortening, and 21% had evidence of pulmonary hypertension. Abnormal right ventricular global longitudinal strain and abnormal right ventricular free wall strain were present in 35% and 40% of patients, respectively. No echocardiographic variables differed between or across pediatric acute respiratory distress syndrome severity. In multivariable analyses, right ventricular global longitudinal strain was independently associated with PICU mortality (odds ratio, 3.57 [1.33–9.60]; p = 0.01), whereas right ventricular global longitudinal strain, right ventricular free wall strain, and the presence of pulmonary hypertension were independently associated with lower probability of extubation (subdistribution hazard ratio, 0.46 [0.26–0.83], p = 0.01; subdistribution hazard ratio, 0.58 [0.35–0.98], p = 0.04; and subdistribution hazard ratio, 0.49 [0.26–0.92], p = 0.03, respectively). Conclusions: Early ventricular dysfunction and pulmonary hypertension were detectable, prevalent, and independent of lung injury severity in children with pediatric acute respiratory distress syndrome. Right ventricular dysfunction was associated with PICU mortality, whereas right ventricular dysfunction and pulmonary hypertension were associated with lower probability of extubation.

https://ift.tt/2A7QdS0

Assessing Variability in Hospital-Level Mortality Among U.S. Medicare Beneficiaries With Hospitalizations for Severe Sepsis and Septic Shock*

Objectives: To assess the variability in short-term sepsis mortality by hospital among Centers for Medicare and Medicaid Services beneficiaries in the United States during 2013–2014. Design: A retrospective cohort design. Setting: Hospitalizations from 3,068 acute care hospitals that participated in the Centers for Medicare and Medicaid Services inpatient prospective payment system in 2013 and 2014. Patients: Medicare fee-for-service beneficiaries greater than or equal to 65 years old who had an inpatient hospitalization coded with present at admission severe sepsis or septic shock. Interventions: None. Measurements and Main Results: Individual level mortality was assessed as death at or within 7 days of hospital discharge and aggregated to calculate hospital-level mortality rates. We used a logistic hierarchal linear model to calculate mortality risk-adjusted for patient characteristics. We quantified variability among hospitals using the median odds ratio and calculated risk-standardized mortality rates for each hospital. The overall crude mortality rate was 34.7%. We found significant variability in mortality by hospital (p

https://ift.tt/2QIvhGq

Patient-Directed Music Therapy in the ICU

No abstract available

https://ift.tt/2A8vY6G

Adding to the Repertoire of Scoring Systems in Acute-on-Chronic Liver Failure: Will Simplicity Be Outdone by Complexity?*

No abstract available

https://ift.tt/2A7sEbQ

Inflammation, Cerebral Vasospasm, and Brain Injury in Subarachnoid Hemorrhage—A Shifting Paradigm and a New Beginning*

No abstract available

https://ift.tt/2A6DkHM

Case Fatality and Adverse Outcomes Are Reduced in Pregnant Women With Severe Sepsis or Septic Shock Compared With Age-Matched Comorbid-Matched Nonpregnant Women

Objectives: Case fatality in pregnancy-associated severe sepsis or septic shock appears reduced compared with nonpregnant women with severe sepsis or septic shock. It remains unclear if this difference is due to pregnancy or better baseline health status, among others. Our study compared adverse outcomes of pregnancy-associated severe sepsis or septic shock with nonpregnant women with severe sepsis or septic shock while controlling for age and chronic comorbidities. Design: Retrospective cohort study. Setting: Nationwide Inpatient Sample, a stratified sample of 20% acute care hospital admissions in the United States. Each entry includes patient and hospital characteristics as well as International Classification of Diseases, 9th revision, Clinical Modification, diagnoses and procedures. Subjects: Women of childbearing age (15–44 yr) with severe sepsis or septic shock–related hospitalizations during 1998–2012 identified using International Classification of Diseases, 9th revision, Clinical Modification, codes. Outcomes: Case fatality, hospital length of stay, length of stay until death, number of organ failures, rates of mechanical ventilation, and hemodialysis were compared in women according to pregnancy status, controlling for age, and chronic comorbidities. Measurements and Main Results: We identified 5,968 pregnancy-associated severe sepsis or septic shock and 85,240 nonpregnant women with severe sepsis or septic shock hospitalizations. Crude case fatality of pregnancy-associated severe sepsis or septic shock (9.6%) was lower than nonpregnant women with severe sepsis or septic shock (16.8%). The rate ratio for case fatality adjusted for socioeconomic status and race was 0.57 (95% CI, 0.52–0.62) while sequential adjustments for age and chronic comorbidities did not eliminate the association (rate ratio, 0.62 [95% CI, 0.57–0.68]) and 0.63 [95% CI, 0.57–0.68], respectively). Pregnancy-associated severe sepsis or septic shock was associated with shorter hospital length of stay (–0.83 d [95% CI, –1.32 to –0.34 d]), longer length of stay until death (2.61 d; [95% CI, 1.28–3.94 d]), and fewer organ failures (rate ratio, 0.95 [95% CI, 0.94–0.97]). Conclusions: Case fatality and adverse outcomes are reduced in women with pregnancy-associated severe sepsis or septic shock compared with nonpregnant women with severe sepsis or septic shock, and this is not explained by differences in age or chronic comorbidities alone. A less severe presentation of sepsis or protective effect of pregnancy may account for the difference observed with pregnancy-associated severe sepsis or septic shock.

https://ift.tt/2QLJRNg

Ultrasound Assessment of the Change in Carotid Corrected Flow Time in Fluid Responsiveness in Undifferentiated Shock

Objectives: Adequate assessment of fluid responsiveness in shock necessitates correct interpretation of hemodynamic changes induced by preload challenge. This study evaluates the accuracy of point-of-care Doppler ultrasound assessment of the change in carotid corrected flow time induced by a passive leg raise maneuver as a predictor of fluid responsiveness. Noninvasive cardiac output monitoring (NICOM, Cheetah Medical, Newton Center, MA) system based on a bioreactance method was used. Design: Prospective, noninterventional study. Setting: ICU at a large academic center. Patients: Patients with new, undifferentiated shock, and vasopressor requirements despite fluid resuscitation were included. Patients with significant cardiac disease and conditions that precluded adequate passive leg raising were excluded. Interventions: Carotid corrected flow time was measured via ultrasound before and after a passive leg raise maneuver. Predicted fluid responsiveness was defined as greater than 10% increase in stroke volume on noninvasive cardiac output monitoring following passive leg raise. Images and measurements were reanalyzed by a second, blinded physician. The accuracy of change in carotid corrected flow time to predict fluid responsiveness was evaluated using receiver operating characteristic analysis. Measurements and Main Results: Seventy-seven subjects were enrolled with 54 (70.1%) classified as fluid responders by noninvasive cardiac output monitoring. The average change in carotid corrected flow time after passive leg raise for fluid responders was 14.1 ± 18.7 ms versus –4.0 ± 8 ms for nonresponders (p

https://ift.tt/2A7JNC1

Dynamic Prognostication in Critically Ill Cirrhotic Patients With Multiorgan Failure in ICUs in Europe and North America: A Multicenter Analysis*

Objectives: To evaluate the Chronic Liver Failure-Consortium Acute on Chronic Liver Failure score in acute on chronic liver failure patients admitted to ICUs from different global regions and compare discrimination ability with previously published scores. Design: Retrospective pooled analysis. Setting: Academic ICUs in Canada (Edmonton, Vancouver) and Europe (Paris, Barcelona, Chronic liver failure/Acute-on-Chronic Liver Failure in Cirrhosis [CANONIC] study). Patients: Sample of analysis of 867 cirrhotic patients with acute on chronic liver failure admitted to ICU. Cumulative incidence functions of death were estimated by acute on chronic liver failure grade at admission and at day 3. Survival discrimination abilities of Chronic Liver Failure-Consortium Acute on Chronic Liver Failure, Model for End-Stage Liver Disease, Acute Physiology and Chronic Health Evaluation II, and Child-Turcotte-Pugh scores were compared. Interventions: ICU admission for organ support. Measurements and Main Results: At admission 169 subjects (19%) had acute on chronic liver failure 1, 302 (35%) acute on chronic liver failure 2, and 396 (46%) had acute on chronic liver failure 3 with 90-mortality rates of 33%, 40%, and 74%, respectively (p 70), decisions regarding transition to palliation should be explored between patient families and the ICU providers after a short trial of therapy.

https://ift.tt/2QNI6zj

Extracorporeal Membrane Oxygenation Can Successfully Support Patients With Severe Acute Respiratory Distress Syndrome in Lieu of Mechanical Ventilation

Objectives: Extracorporeal membrane oxygenation is increasingly used in the management of severe acute respiratory distress syndrome. With extracorporeal membrane oxygenation, select patients with acute respiratory distress syndrome can be managed without mechanical ventilation, sedation, or neuromuscular blockade. Published experience with this approach, specifically with attention to a patient's respiratory drive following cannulation, is limited. Design: We describe our experience with three consecutive patients with severe acute respiratory distress syndrome supported with right jugular-femoral configuration of venovenous extracorporeal membrane oxygenation without therapeutic anticoagulation as an alternative to lung-protective mechanical ventilation. Outcomes are reported including daily respiratory rate, vital capacities, and follow-up pulmonary function testing. Results: Following cannulation, patients were extubated within 24 hours. During extracorporeal membrane oxygenation support, all patients were able to maintain a normal respiratory rate and experienced steady improvements in vital capacities. Patients received oral nutrition and ambulated daily. At follow-up, no patients required supplemental oxygen. Conclusions: Our results suggest that venovenous extracorporeal membrane oxygenation can provide a safe and effective alternative to lung-protective mechanical ventilation in carefully selected patients. This approach facilitates participation in physical therapy and avoids complications associated with mechanical ventilation.

https://ift.tt/2A7s1Po

Intracranial Pressure Trajectories: A Novel Approach to Informing Severe Traumatic Brain Injury Phenotypes*

Objectives: Intracranial pressure in traumatic brain injury is dynamic and influenced by factors like injury patterns, treatments, and genetics. Existing studies use time invariant summary intracranial pressure measures thus potentially losing critical information about temporal trends. We identified longitudinal intracranial pressure trajectories in severe traumatic brain injury and evaluated whether they predicted outcome. We further interrogated the model to explore whether ABCC8 polymorphisms (a known cerebraledema regulator) differed across trajectory groups. Design: Prospective observational cohort. Setting: Single-center academic medical center. Patients: Four-hundred four severe traumatic brain injury patients. Interventions: None. Measurements and Main Results: We used group-based trajectory modeling to identify hourly intracranial pressure trajectories in days 0–5 post traumatic brain injury incorporating risk factor adjustment (age, sex, Glasgow Coma Scale 6score, craniectomy, primary hemorrhage pattern). We compared 6-month outcomes (Glasgow Outcome Scale, Disability Rating Scale, mortality) and ABCC8 tag-single-nucleotide polymorphisms associated with cerebral edema (rs2237982, rs7105832) across groups. Regression models determined whether trajectory groups predicted outcome. A six trajectory group model best fit the data, identifying cohorts differing in initial intracranial pressure, evolution, and number/proportion of spikes greater than 20 mm Hg. There were pattern differences in age, hemorrhage type, and craniectomy rates. ABCC8 polymorphisms differed across groups. GOS (p = 0.006), Disability Rating Scale (p = 0.001), mortality (p

https://ift.tt/2QT5YSn

Trends in social determinants of child health and perinatal outcomes in European countries 2005-2015 by level of austerity imposed by governments: a repeat cross-sectional analysis of routinely available data

Objective

To assess whether the level of austerity implemented by national governments was associated with adverse trends in perinatal outcomes and the social determinants of children's health (SDCH) in rich countries

Design

Longitudinal ecological study of country-level time trends in perinatal outcomes and SDCH and from 2005 to 2015.

Setting and participants

16 European countries using available data from the International Monetary Fund, the Organisation for Economic Co-operation and Development and Eurostat.

Main outcome measures

Trends in perinatal outcomes (low birth weight (LBW); infant mortality) and the SDCH: child poverty rates; severe material deprivation in families with primary education; preschool investment in three time periods: 2005–2007, 2008–2010 and 2012–2015. Outcomes were compared according to the cyclically adjusted primary balance (CAPB, differences between 2013 and 2009) as a measure of austerity, stratified in tertiles. Generalised estimating equation models of repeated measures were used to assess time trend differences in three periods.

Results

Countries with higher levels of austerity had worse outcomes, mainly at the last study period. Material deprivation increased during the period 2012–2015 in those countries with higher CAPB (interaction CAPB-period 2012–2015, B: 5.62: p<0.001), as did LBW (interaction CAPB-period 2012–2015, B: 0.25; p=0.004).

Conclusions

Countries that implemented more severe austerity measures have experienced increasing LBW, and for families with primary education also increasing material deprivation, worsening the negative impact of economic crisis. Reversing austerity policies that impact children is likely to improve child health outcomes.

https://ift.tt/2yfiDIq

Multimodal MRI-based classification of migraine: using deep learning convolutional neural network

Recently, deep learning technologies have rapidly expanded into medical image analysis, including both disease detection and classification. As far as we know, migraine is a disabling and common neurological d...

https://ift.tt/2yhspd3

Immunohistochemistry in Surgical Pathology

No abstract available

https://ift.tt/2OU6oud

Applications of Immunohistochemistry to Endocrine Pathology

The role of immunohistochemistry (IHC) in endocrine pathology is similar to that in other organ systems in that it can aid in the subclassification of tumors within an organ, confirm site of primary in metastatic disease, provide prognostic information, identify underlying genetic alterations, and predict response to treatment. Although most endocrine tumors do not require IHC to render a diagnosis, there are certain scenarios in which IHC can be extremely helpful. For example, in thyroid, IHC can be used to support tumor dedifferentiation, in the adrenal it can aid in the diagnosis of low-grade adrenocortical carcinomas, and in paragangliomas it can help identify tumors arising as part of an inherited tumor syndrome. This review will focus on the applications of IHC in tumors of the thyroid, parathyroids, adrenals, and paraganglia in adults.

https://ift.tt/2CcUftr

Diagnostic and Predictive Immunohistochemistry for Non–Small Cell Lung Carcinomas

Non–small cell lung carcinoma (NSCLC) accounts for significant morbidity and mortality worldwide, with most patients diagnosed at advanced stages and managed increasingly with targeted therapies and immunotherapy. In this review, we discuss diagnostic and predictive immunohistochemical markers in NSCLC, one of the most common tumors encountered in surgical pathology. We highlight 2 emerging diagnostic markers: nuclear protein in testis (NUT) for NUT carcinoma; SMARCA4 for SMARCA4-deficient thoracic tumors. Given their highly aggressive behavior, proper recognition facilitates optimal management. For patients with advanced NSCLCs, we discuss the utility and limitations of immunohistochemistry (IHC) for the "must-test" predictive biomarkers: anaplastic lymphoma kinase, ROS1, programmed cell death protein 1, and epidermal growth factor receptor. IHC using mutant-specific BRAF V600E, RET, pan-TRK, and LKB1 antibodies can be orthogonal tools for screening or confirmation of molecular events. ERBB2 and MET alterations include both activating mutations and gene amplifications, detection of which relies on molecular methods with a minimal role for IHC in NSCLC. IHC sits at the intersection of an integrated surgical pathology and molecular diagnostic practice, serves as a powerful functional surrogate for molecular testing, and is an indispensable tool of precision medicine in the care of lung cancer patients.

https://ift.tt/2OU6kut

Diagnostic Immunohistochemistry for Soft Tissue and Bone Tumors: An Update

Although some soft tissue and bone tumors can be identified based on histologic features alone, immunohistochemistry plays a critical diagnostic role for most mesenchymal tumor types. The discovery of recurrent genomic alterations in many benign and malignant mesenchymal neoplasms has added important biologic insights and expanded the spectrum of some diagnostic subgroups. Some tumors are defined by unique genomic alterations, whereas others share abnormalities that are not tumor-specific and can be observed in a sometimes broad range of biologically unrelated neoplasms. We herein focus on novel immunohistochemical markers, based on molecular genetic alterations, which are particularly useful in the diagnostic workup of selected groups of soft tissue and bone tumors, including recently described entities, specifically round cell sarcomas (Ewing sarcoma, CIC-rearranged sarcoma, and BCOR-rearranged sarcoma), vascular tumors (epithelioid hemangioma, epithelioid hemangioendothelioma, and pseudomyogenic hemangioendothelioma), SMARCB1-deficient neoplasms, adipocytic tumors (spindle cell/pleomorphic lipoma, atypical spindle cell lipomatous tumor, and conventional atypical lipomatous tumor), giant cell-rich bone tumors (giant cell tumor of bone and chondroblastoma), and biphenotypic sinonasal sarcoma. Given the complex nature of sarcoma classification, and the rarity of many mesenchymal tumor types, careful integration of clinical presentation, imaging features, histology, immunophenotype, and cytogenetic/molecular alterations is crucial for accurate diagnosis of soft tissue and bone tumors.

https://ift.tt/2Cb5aUG

Immunohistochemical Pitfalls in Genitourinary Pathology: 2018 Update

Immunohistochemistry may be a very useful adjunct to morphologic diagnosis in many areas of surgical pathology, including genitourinary pathology. In this review, we address common diagnostic dilemmas where immunophenotypic analysis may be utilized and we highlight pitfalls specific to each scenario. For prostate, we review the diagnosis of limited prostatic adenocarcinoma and the distinction of high-grade prostatic adenocarcinoma from urothelial carcinoma. We also cover markers of urothelial lineage in the diagnosis of metastatic carcinoma of unknown primary site. In the kidney, distinction of poorly differentiated renal cell carcinoma from urothelial carcinoma and epithelioid angiomyolipoma, adjuncts to the recognition of hereditary renal neoplasia, and the diagnosis of metastatic renal cell carcinoma are discussed. Finally, for testis we address distinction of germ cell tumors from sex cord-stromal tumors, as well as the diagnosis of metastatic germ cell tumors.

https://ift.tt/2OU6fHb

Current CPT Coding and Payment Policy Implications for Immunohistology Services

Immunohistology is essential to the practice of modern surgical and cytopathology. There are 3 major types of immunohistologic services provided in clinical practice: traditional immunohistochemistry, morphometric analysis of tumor immunohistochemistry, and immunofluorescence. Proper Current Procedural Terminology coding for these services has been updated to reflect current medical practice. Subsequent to changes in the Current Procedural Terminology coding structure for these services, the valuation of these services have been reviewed by the American Medical Association/Specialty Society Relative Value Update Committee and new valuations instituted by the Centers for Medicare and Medicaid Services. Although valuations for services may be established, the circumstances of payment may be affected by Medicare Contractor's Local Coverage Determinations or service limits imposed by the National Correct Coding Initiative.

https://ift.tt/2CdeQhk

Neurotoxicity of Anesthesia in Children: Prevention and Treatment

Abstract

Purpose of review

The purpose of this review is to summarize the current evidence regarding the impact of the exposure to anesthetic and sedative agents on neurodevelopment during the period of rapid brain growth in the first 3 years of life. Though much of the definitive data demonstrating anesthesia-induced neurotoxicity has come from studies in young animals, the focus of this review is on emerging human data.

Recent findings

In 2016, the first prospective trials investigating the neurodevelopmental impact of early anesthetic exposure (GAS and PANDA studies) were published, both showing no significant impact on IQ from a single brief anesthetic. More recent population cohort analyses have shown varying, but minimal, impacts from early anesthetic exposure on academic performance and IQ, much smaller than that of maternal education and other environmental factors.

Summary

Animal and human data document that post-anesthetic neurotoxicity is a genuine phenomenon, but its long-term clinical significance is uncertain. Most experts would agree that a single, brief anesthetic likely has no significant impact on neurodevelopment, but it is yet to be determined whether longer exposures or multiple anesthetics are associated with subsequent learning issues. Future research is aimed at determining the mechanisms of neuronal injury from exposure to anesthetic and sedative agents, adjunctive medications that may prevent or ameliorate this injury, and therapeutic approaches such as early intervention that can enhance recovery. While these studies are underway, it is recommended that exposure to anesthetic and sedative agents be minimized in young children and consideration be given to alternative methods of immobilization for nonpainful procedures such as radiologic imaging.

https://ift.tt/2OTyFB8

Current Treatment Strategies and Future Treatment Options for Dravet Syndrome

Abstract

Purpose of review

Dravet syndrome is a rare but severe genetic epilepsy that has unique treatment challenges. This is a review of current and future potential treatment options.

Recent findings

Treatment for Dravet syndrome should encompass many aspects of the syndrome such as gait, behavior, and nutrition, as well as focus on seizure control. Many sodium channel blockers should be avoided as they are likely to exacerbate seizures. Current options for treatment include valproic acid, clobazam, stiripentol, and ketogenic diet. Testing is underway for several new treatment options with unique mechanisms of action and therapeutic targets, including the serotonin system and genetic modulation.

Summary

Accurate and early diagnosis of Dravet syndrome will lead to avoidance of medications that may exacerbate seizures. Additionally, a multi-disciplinary approach and careful planning for management of episodes of status epilepticus may lead to improved outcomes. Ongoing research for novel approaches to treatment creates optimism for future improvement in outcomes.

https://ift.tt/2CbtyFM

Highlights of the 22nd Annual Scientific Meeting of the Australasian Musculoskeletal Imaging Group [AMSIG] 2018, Gold Coast, Queensland, Australia

https://ift.tt/2Opr8dW

Health seeking behaviour and delayed management of tuberculosis patients in rural Bangladesh

Early diagnosis of tuberculosis (TB) and involvement of the public-private partnership are critical to eradicate TB. Patients need to receive proper treatment through the National Tuberculosis Control Programm...

https://ift.tt/2A7gijP

Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure

Incomplete virologic suppression results in mutations associated with resistance and is a major obstacle to disease control. We analyzed the genotypic profiles of HIV-1 patients at the time of the first virolo...

https://ift.tt/2QLOVRT

Epidemiology of hepatitis B, C and D in Malawi: systematic review

Viral hepatitis is an important public health issue in sub-Saharan Africa. Due to rising mortality from cirrhosis and hepatocellular carcinoma and limited implementation of screening and treatment programmes, ...

https://ift.tt/2A7wpOw

Modified genome comparison method: a new approach for identification of specific targets in molecular diagnostic tests using Mycobacterium tuberculosis complex as an example

The first step of designing any genome-based molecular diagnostic test is to find a specific target sequence. The modified genome comparison method is one of the easiest and most comprehensive ways to achieve ...

https://ift.tt/2QPgv0M

The Economic Burden of Pediatric Asthma in the United States: Literature Review of Current Evidence

Abstract

Asthma is a chronic respiratory disease that is widespread throughout the US population and disproportionately affects children. This literature review aimed to identify recent information regarding the economic burden of pediatric asthma in the US. MEDLINE, EMBASE, Econlit, and PsycINFO databases and gray literature sources were searched from January 2012 to January 2018 to capture relevant publications. Publications reporting on healthcare resource utilization and/or healthcare costs of pediatric asthma were included (n = 8). Total direct costs of pediatric asthma were US$5.92 billion in 2013. Average annual costs per child ranged from US$3076 to US$13612. Across studies, pharmacy (US$1027–2120), inpatient (US$337–2016) and outpatient (US$1049–8039) costs were the primary contributors to healthcare costs. Inpatient and emergency department (ED) visits exerted a high economic burden. For instance, the national annual cost of asthma-related hospitalizations was estimated at US$1.59 billion in 2009, while estimates of costs-per-hospitalization (2010) and charges-per-discharge (2009) were US$3600 and US$8406, respectively. The total cost of ED visits to Medicaid was estimated at US$272 million in 2010. In a mixed-insurance population, ED cost estimates ranged from US$152 to US$172 annually per patient. Invariably, costs for children with asthma were significantly greater than for children without. Pediatric asthma imposes a significant economic burden to the US healthcare system. Children with asthma have significantly higher healthcare resource utilization and costs than children without asthma.

https://ift.tt/2Oncsfr

Treatment of Persistent Postural-Perceptual Dizziness (PPPD) and Related Disorders

Abstract

Purpose of review

Persistent postural-perceptual dizziness (PPPD) is a newly defined disorder of functional dizziness that in the International Classification of Diseases in its 11th revision (ICD-11) supersedes phobic postural vertigo and chronic subjective dizziness. Despite efforts to unify the diagnosis of functional (somatoform) dizziness, patients will present with a variety of triggers, perpetuating factors, and comorbidities, requiring individualized treatment. This article will review different treatment strategies for this common functional neurological disorder and provide practical recommendations for tailored therapy.

Recent findings

An emerging understanding of the underlying pathophysiology that considers vestibular, postural, cognitive, and emotional aspects can enable patients to profit from vestibular rehabilitation, as well as cognitive-behavioral therapy (CBT). Crucially, approaches from CBT should inform and augment physiotherapeutic techniques, and, on the other hand, vestibular exercises or relaxation techniques can be integrated into CBT programs. Antidepressant medication might further facilitate rehabilitation, though the mechanisms are yet to be elucidated, and the level of evidence is low.

Summary

In PPPD and related disorders, vestibular rehabilitation combined with CBT, and possibly supported by medication, can help patients escape a cycle of maladaptive balance control, recalibrate vestibular systems, and regain independence in everyday life.

https://ift.tt/2RLZPsg

Oncogenic Epithelial Reprogramming Drives Neuroendocrine Cancers [Research Watch]

A set of oncogenic drivers induce the neuroendocrine reprogramming of prostate and lung epithelial cells.

https://ift.tt/2yygirf

Telisotuzumab Vedotin Has Activity in Patients with MET-Positive NSCLC [Research Watch]

The MET-targeting antibody–drug conjugate telisotuzumab vedotin (Teliso-V) is well tolerated in patients.

https://ift.tt/2yfagwr

NIH Budget Makes Up Ground [News in Brief]

Agency sees a substantial boost for the fourth consecutive year, closes gap on medical inflation.

https://ift.tt/2yAjT8e

c-KIT Has a Tumor-Suppressive Role via Induction of Apoptosis [Research Watch]

In addition to its oncogenic kinase activity, c-KIT acts as a dependence receptor to promote apoptosis.

https://ift.tt/2ybxtzx

Mevalonate Pathway Inhibitors May Be Effective Cancer Vaccine Adjuvants [Research Watch]

Lipophilic statins and bisphosphonates may serve as potent adjuvants for cancer vaccines.

https://ift.tt/2yzg8Qf

Technique Pinpoints Oncogenic BRCA1 Mutations [News in Brief]

Effects of nearly 4,000 alterations catalogued.

https://ift.tt/2yf9Shw

Antibody-Dependent Cellular Cytotoxicity Renders Macrophages Immunosuppressive [Research Watch]

Therapeutic antibodies result in ADCP that upregulates PD-L1 and IDO on macrophages.

https://ift.tt/2yzwnwN

Deletion of ATM in tumor but not endothelial cells improves radiation response in a primary mouse model of lung adenocarcinoma

Stereotactic body radiation therapy is utilized to treat lung cancer. The mechanism of tumor response to high dose RT (HDRT) is controversial, with competing hypotheses of increased direct tumor cell killing vs indirect effects on stroma including endothelial cells. Here we used dual recombinase technology in a primary murine lung cancer model to test whether tumor cells or endothelial cells are critical HDRT targets. Lenti-Cre deleted one or two copies of Atm (KPAFL/+ or KPAFL/FL), whereas adeno-FlpO infected mice expressed Cre in endothelial cells to delete one or both copies of Atm (KPVAFL/+ or KPVAFL/FL) to modify tumor cell or endothelial cell radiosensitivity, respectively. Deletion of Atm in either tumor cells or endothelial cells had noimpact on tumor growth in the absence of radiation. Despite increased endothelial cell death in KPVAFL/FL mice following irradiation, tumor growth delay was not significantly increased. In contrast, a prolonged tumor growth delay was apparent in KPAFL/FL mice. Primary tumor cell lines lacking Atm expression also demonstrated enhanced radiosensitivity as determined via a clonogenic survival assay. These findings indicate that tumor cells, rather than endothelial cells, are critical targets of HDRT in primary murine lung cancer.

https://ift.tt/2Op0fqo

Pomalidomide inhibits PD-L1 to promote anti-tumor immunity

Thalidomide-like drugs have been approved for the treatment of human multiple myeloma (MM), with their direct antitumor effects and immunomodulatory functions well documented. However, the exact molecular mechanisms that govern these effects remain unclear. Here we demonstrate that pomalidomide (POM) promotes immune response by inhibiting expression of PD-L1. POM inhibited PD-L1 expression on tumor cells to promote cytotoxic T lymphocyte (CTL) activity in vitro and suppressed PD-L1 upregulation on antigen-presenting cells (APC) to prevent peptide-induced T cell tolerance. Knockout of PD-L1 on tumor cells or in mice completely eliminated the immunomodulatory effect of POM. Furthermore, POM synergized with other immunotherapies to improve anticancer therapy. Taken together, this study identifies a new mechanism for the immunomodulatory functions of POM in cancer therapy. These results also offer a clinical approach for blocking PD-L1 induction and potentially promoting anti-tumor immunity.

https://ift.tt/2IRXmbN

15- and 18-Month, 4-Year Well-Child Visits Most Often Missed

FRIDAY, Oct. 12, 2018 -- Well-child visits (WCVs) at 15 months, 18 months, and four years are the most commonly missed among children of low-income families, according to a study published online Oct. 10 in Pediatrics. Elizabeth R. Wolf, M.D.,...

https://ift.tt/2pRVzuE

Multicomponent Intervention Can Reduce Sitting Time at Work

FRIDAY, Oct. 12, 2018 -- A multicomponent intervention (Stand More At [SMArT] Work) can reduce sitting time over the short, medium, and long terms, according to a study published online Oct. 10 in The BMJ. Charlotte L. Edwardson, Ph.D., from the...

https://ift.tt/2NCuxkg

Violent Video Games Tied to Physical Aggression

FRIDAY, Oct. 12, 2018 -- Playing violent video games is associated with subsequent increases in physical aggression, according to research published online Oct. 2 in the Proceedings of the National Academy of Sciences. Anna T. Prescott, Ph.D., from...

https://ift.tt/2pRVGGA

FDA Approves New DNA-Based Test to Verify Blood Compatibility

FRIDAY, Oct. 12, 2018 -- The U.S. Food and Drug Administration has approved the ID CORE XT DNA-based test to help doctors verify blood compatibility before a transfusion. Patients who need repeated transfusions, such as those with sickle cell...

https://ift.tt/2NELs5L

Flu Vaccine Cuts Hospitalization Rates in Pregnant Women

FRIDAY, Oct. 12, 2018 -- Among pregnant women, the flu vaccination is effective at reducing the risk for flu-related hospitalizations, according to a study published online Oct. 11 in Clinical Infectious Disease. Mark G. Thompson, Ph.D., from the...

https://ift.tt/2pPe6HJ

Comparative Efficacy of Alendronate upon Vertebral Bone Mineral Density and Fracture Rates in East Asians Versus Non-East Asians with Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis

Horm Metab Res 2018; 50: 738-746
DOI: 10.1055/a-0741-8300

Bisphosphonates, such as alendronate, have become the most widely used and effective anti-resorptive therapy for postmenopausal osteoporosis. Previous genetic studies suggest that ethnicity may drive differing responses to bisphosphonate therapy in East Asians and non-East Asians. Therefore, the aim of this study was to comparatively evaluate the efficacy of alendronate upon lumbar spinal BMD and vertebral fracture rates in East Asians and non-East Asians with postmenopausal osteoporosis. MEDLINE, EMBASE, and Cochrane CENTRAL were searched for relevant randomized controlled trials (RCTs) comparing the efficacy of alendronate versus placebo (or calcium/mineral and/or Vitamin D or hormone replacement therapy) in primary postmenopausal osteoporotic women. We calculated the weighted mean differences (WMDs) for lumbar spinal BMD and the risk ratios (RRs) for vertebral fracture risk along with their respective 95% confidence intervals (CIs). From an initial set of 445 non-duplicate records, 13 full-text articles were finally included in this meta-analysis consisting of four East Asian RCTs and nine non-East Asian RCTs. Alendronate therapy displayed significant effects in improving lumbar spinal BMD in both East Asians [WMD (95% CI)=5.30 (0.32–10.29), p=0.037] and non-East Asians [WMD (95% CI)=5.73 (3.61–7.85), p=0.000]. Alendronate therapy did not display significant effects upon vertebral fracture risk in East Asians [RR (95% CI)=0.41 (0.06–2.73), p=0.358] but did display a significant effect upon lowering vertebral fracture risk in non-East Asians [RR (95% CI)=0.55 (0.42–0.72), p=0.000]. These findings suggest that ethnicity may affect the efficacy of bisphosphonate therapy in postmenopausal osteoporotic women.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2ISGwt3

Effect of Selenium Supplementation on Lipid Profile: A Systematic Review and Meta-Analysis

Horm Metab Res 2018; 50: 715-727
DOI: 10.1055/a-0749-6655

Selenium is an essential mineral that plays a key role in plenty of major metabolic processes. A growing body of literature has shown that selenium deficiency leads to an increase in plasma TC and TG levels. This study explores the effect of selenium supplementation on serum level of lipid profile [total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low density lipoprotein (VLDL)]. We systematically searched PubMed/MEDLINE, ISI/WOS, and Scopus (from their commencements to Jan 2016) to identify the papers investigating the association between the intake of selenium and lipid profile. Data extracted from the relevant studies were screened. The pooled standardized mean difference was estimated using the random or fixed effects model. Heterogeneity among the studies was assessed using Q-test. Of the potentially relevant articles screened, 11 articles including 1221 participants were included in this meta-analysis. Results of meta-analysis showed that intake of selenium resulted in a statistically significant improvement in TC, [(SMD): –0.13, 95% CI: (–0.24, –0.02)], TG [(SMD): –0.19, 95% CI: (–0.38, –0.01)] and VLDL [(SMD): –0.34, 95% CI: (–0.63, –0.05)]. The selenium supplementation did not significantly improve lipid profile such as LDL [(SMD): –0.08, 95% CI: (–0.036, 0.19)], HDL [(SMD): 0.01, 95% CI: (–0.164, 0.18)], HDL/TC ratio [(SMD): 0.025, 95% CI: (–0.11, 0.16)], non-HDL-C [(SMD): 0.018, 95% CI: (–0.13, 0.16)]. This meta-analysis suggests that the effect of selenium supplementation on the serum levels of TG and VLDL is marginally significant. However, the supplementation has no effect on other serum lipids. Moreover, the study shows that the effect of selenium supplementation on lipid profile is negative.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2yf6nrl

Bone Mineral Density is Unaltered in Women with Polycystic Ovary Syndrome

Horm Metab Res 2018; 50: 754-760
DOI: 10.1055/a-0733-7768

Context The effects of endocrine aberrations associated with polycystic ovary syndrome (PCOS) on bone mineral density (BMD) in young women is a matter of debate. Objectives To compare BMD in young women with PCOS to age and body mass index (BMI) matched controls and to elucidate its correlation to BMI, insulin resistance and serum testosterone. Design and Methods We recruited 60 women with PCOS aged 14-24 years, diagnosed based on Rotterdam 2003 criteria, and 58 age matched controls. BMD was measured by dual energy X-ray absorptiometry. In addition, these subjects underwent biochemical and hormonal analysis including oral glucose tolerance test, calculation of Homeostatic Model Assessment–Insulin Resistance Index, measurement of serum thyroxine, thyrotropin, prolactin, total testosterone, dehydroepiandrosterone sulfate, follicular phase luteinizing hormone and follicle stimulating hormone. Results There was no difference of BMD between women with PCOS and control women (1.103±0.08 vs 1.126±0.083 g/cm2; p=0.122). In subgroup analysis based on BMI, BMD in obese women with PCOS was significantly higher than their overweight and lean counterparts at lumbar spine (p<0.001), neck of femur (p=0.005) and total hip (p<0.001). BMD was not different at any site between oligomenorrheic and non-oligomenorrheic women with PCOS. It positively correlated with BMI, waist and hip circumference in women with PCOS. No correlation was found with HOMA-IR or Testosterone. Conclusions BMI is the most important determinant of BMD in women with PCOS. BMD is not different between healthy young women and those with PCOS.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

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Risk of Malignancy in Thyroid Nodules Using the American College of Radiology Thyroid Imaging Reporting and Data System in the NIFTP Era

Horm Metab Res 2018; 50: 735-737
DOI: 10.1055/a-0743-7326

Recently, the American College of Radiology (ACR) proposed a Thyroid Imaging Reporting and Data System (TI-RADS) for thyroid nodules based on ultrasonographic features. It is important to validate this classification in different centres. The present study evaluated the risk of malignancy in solid nodules>1 cm using ACR TI-RADS. The risk of malignancy was defined including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and after its exclusion from malignant tumours. For the present study, the original images were revised, and each nodule was assigned to one of the TI-RADS levels proposed for solid nodules: TR3, TR4, or TR5. This risk of malignancy was significantly different for the three levels: 1.7%, 11.2%, and 60.6% for TR3, TR4, and TR5, respectively, when NIFTP was included, and 0.6%, 7.9%, and 60.2% for TR3, TR4, and TR5, respectively, when NIFTP was excluded from malignant tumours. The nodules corresponding to NIFTP were classified according to ACR as TR3 in 28.5% of cases, TR4 in 67.8%, and TR5 in only 3.5%. The nodules corresponding to cancer were classified according to ACR as TR3 in only 2.3% of cases, TR4 in 27%, and TR5 in 70.5%. In conclusion, this study shows the validity of the ACR TI-RADS for solid thyroid nodules, even after the exclusion of NIFTP from malignant tumours.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Effects of Stratified Vitamin D Supplementation in Middle-Aged and Elderly Individuals with Vitamin D Insufficiency

Horm Metab Res 2018; 50: 747-753
DOI: 10.1055/a-0746-5031

The incidence of vitamin D deficiency is high globally, and vitamin D supplementation draws particular attention. The objective of this study was to investigate the effects of stratified vitamin D supplementation in middle-aged and elderly individuals with vitamin D insufficiency in Beijing. A total of 448 subjects aged over 40 years old were selected from a community in Beijing. Among them, 100 middle-aged and elderly people with vitamin D insufficiency were randomly selected on a voluntary basis. They were further divided into control group and intervention group. The control group received health education and lifestyle guidance, and the intervention group received lifestyle guidance and vitamin D supplementation for nine months. The doses were stratified as follows: for vitamin D insufficiency, oral vitamin D3 supplement was given at 5000 IU/w; for mild vitamin D deficiency, oral vitamin D3 supplement was given at 10 000 IU/w; for severe vitamin D deficiency, oral vitamin D3 supplement was given at 15 000 IU/w. Safety evaluation was conducted after three-month treatment. The intervention group consisted of 8%, 62%, and 30% of cases who had vitamin D insufficiency, mild vitamin D deficiency, and severe vitamin D deficiency, respectively, which were similar with the control group. It showed that the blood 25(OH)D level increased significantly in the intervention group, from 14.30±4.30 ng/ml to 33.62±6.99 ng/ml (p<0.001), in contrast to insignificant change in the control group. Stratified vitamin D supplementation effectively increased the blood 25(OH)D level, as well as the number of cases with corrected vitamin D insufficiency or deficiency.
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© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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RNF34 modulates the mitochondrial biogenesis and exercise capacity in muscle and lipid metabolism through ubiquitination of PGC-1 in Drosophila

Abstract

The transcriptional co-activator PGC-1α is a key regulator of mitochondrial function and muscle fiber specification in the skeletal muscle. The E3 ubiquitin ligase RNF34 ubiquitinates PGC-1α and negatively regulates mammalian brown fat cell metabolism. However, the functional importance of RNF34 in the skeletal muscle and its impact on energy metabolism remain unknown. The Drosophila PGC-1 homolog dPGC-1 and its mammalian counterparts have conserved functions in mitochondria and insulin signaling. Here, we showed that the Drosophila RNF34 (dRNF34) ubiquitinates the Drosophila PGC-1α (dPGC-1) and promotes its degradation in HEK293T cells by immunoprecipitation and western blot analysis. This allows us to use Drosophila as a powerful model system to study the physiological role of RNF34 in mitochondrial function and metabolism. In the in vivo studies, by separately expressing two independent UAS-dRNF34 RNAi transgenes driven by the muscle-specific 24B-Gal4 driver, we found that knockdown of dRNF34 specifically in muscle promotes mitochondrial biogenesis, improves negative geotaxis, extends climbing time to exhaustion in moderate aged flies and counteracts high-fat-diet-induced high triglyceride content. Furthermore, we showed that knockdown of dPGC-1 reversed the effects of the dRNF34 knockdown phenotypes described above. Our results reveal that dRNF34 plays an important role in regulating mitochondrial biogenesis in muscle and lipid metabolism through dPGC-1. Thus, inhibition of RNF34 activity provides a potential novel therapeutic strategy for the treatment of age-related muscle dysfunction.

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LncRNA HOTAIR mediates TGF-β2-induced cell growth and epithelial–mesenchymal transition in human lens epithelial cells

Abstract

Posterior capsule opacification (PCO) results from the proliferation, migration, and epithelial–mesenchymal transition (EMT) of residual lens epithelial cells (LECs) and fibers in the capsular bag. Previous reports have demonstrated that transforming growth factor β2 (TGF-β2) affects the cellular processes via modulation of EMT in LECs. However, the mechanisms that underlie the TGF-β2-induced EMT in LECs are still largely unknown. In this study, we confirmed that TGF-β2 induces EMT in SRA01/04 cells via the up-regulation of the long non-coding RNA (lncRNA) HOTAIR. To study the effects of HOTAIR on the proliferation, migration and EMT of SRA01/04 cells as well as the underlying mechanism, we used small interfering RNA (siRNA) to specifically attenuate HOTAIR expression in SRA01/04 cells. CCK8 cell-counting kit was used to examine SRA01/04 cell viability; EdU cell proliferation kit was used to examine SRA01/04 cell proliferation; Transwell system and scratch assays were used to observe cell migration; and qPCR and western blot analysis were used to evaluate EMT progression. We found that inhibition of HOTAIR expression repressed SRA01/04 cell viability, proliferation, migration and prevented the TGF-β2-induced changes in cellular processes via modulation of EMT. Ultimately, we found that HOTAIR affected the TGF-β/Smad signaling pathway. In summary, we elucidated that HOTAIR affected the cell viability, proliferation, and migration in the TGF-β2-induced EMT in SRA01/04 cells and suggested that modulation of HOTAIR may be helpful in PCO prevention and therapy.

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LncRNA-HOTAIR inhibition aggravates oxidative stress-induced H9c2 cells injury through suppression of MMP2 by miR-125

Abstract

Acute myocardial infarction (AMI) is one of the major causes of morbidity and mortality in the world. Ischemia/reperfusion (I/R) injury-induced cardiomyocytes death is the main obstacle that limits the heart function recovery of the AMI patients. Reactive oxygen species (ROS) generated by mitochondria is the main pathological stimulus of cardiomyocytes death during heart I/R injury process. Hence, to understand the underlying mechanism of cardioymocytes proliferation and apoptosis under oxidative stress is crucial for effective AMI therapy. In this study, we found that the expression of long non-coding RNA HOTAIR was significantly downregulated in H9c2 cells in response to oxidative stimuli. HOTAIR knockdown further attenuated H9c2 cells proliferation and accelerated H9c2 cells apoptosis in oxidative stress, while HOTAIR overexpression can protect H9c2 cells from oxidative stress-induced injury. Additionally, HOTAIR acted as a sponge for miR-125. MiR-125 inhibitors restored the H9c2 cells proliferation and migration potential after HOTAIR knockdown in oxidative stress. Meanwhile, MMP2 was identified as a target of miR-125. MMP2 knockdown blocked miR-125 inhibitors' protect effect on H9c2 cells in oxidative stress. Further study demonstrated that HOTAIR inhibition can aggravate oxidative stress-induced H9c2 cells injury through HOTAIR/miR-125/MMP2 axis. Our finding revealed a novel regulatory mechanism for cardiomyocytes proliferation and apoptosis under oxidative stress conditions, which provided a therapeutic approach for myocardium repair after AMI injury.

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Cell-free DNA derived from cancer cells facilitates tumor malignancy through Toll-like receptor 9 signaling-triggered interleukin-8 secretion in colorectal cancer

Abstract

Circulating cell-free DNA (cfDNA) has become a potential diagnostic and prognostic biomarker for colorectal cancer (CRC). In non-cancerous diseases, it has been confirmed that cfDNA can be recognized by Toll-like receptor 9 (TLR9), leading to a significant biological change. Nevertheless, the biological significance of cfDNA and its relationship with TLR9 in tumor malignancy is still unclear. Therefore, the purpose of this study is to explore the biological role of cfDNA in colorectal cancer (CRC). The expression of TLR9 was measured in different CRC cell lines and cancerous samples by RT-PCR or immunohistochemistry, which showed that high expression of TLR9 was significantly correlated with the tumor metastasis, advanced TNM stage and poor prognosis of patients. Then, cfDNA was obtained from fluorouracil (5FU)-induced apoptotic cancer cells in vitro and transfection techniques were used to transfect siRNA and cDNA plasmid for TLR9. Cancer cells were stimulated using isolated cfDNA fragments, and results showed that cfDNA could promote colorectal cancer cell proliferation via TLR9. Meanwhile, we demonstrated that the cfDNA binding to TLR9 could facilitate cell migration and invasion. Finally, we demonstrated that cfDNA initiated downstream TLR9-MyD88 signaling and induced robust release of chemokine interleukin 8 (IL-8), which helped to elucidate the mechanisms underlying these phenomena. Our data suggest that cancer cell-derived cfDNA contributes to cancer progression through activation of TLR9-MyD88 signaling and IL-8 secretion in CRC. These findings provide a novel perspective for understanding of tumor progression and provoke a potential therapeutic target for CRC treatment.

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Phase II randomized study of radiotherapy and three-year androgen deprivation with or without concurrent weekly docetaxel in high-risk localized prostate cancer patients

This trial aimed to assess the activity of weekly docetaxel concurrent with radiotherapy plus three year androgen deprivation in patients with high-risk localized prostate cancer. No statistically significant differences for 5-year biochemical RFS, PFS and OS has been observed when 9 weekly docetaxel cycles were added to conventional treatment. Concurrent weekly docetaxel can be administered safely with standard doses of radiotherapy without a significant increase in the toxicity profile.

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A Spatiotemporal-Constrained Sorting Method for Motion-robust 4D-MRI: A Feasibility Study

In this work, a spatiotemporal-constrained sorting technique was developed to improve 4D-MRI motion-robustness. This sorting technique adapted to optimized sparse k-space acquisition trajectory to reduce motion artifacts due to irregular breathing. Self-gating technique and compressed-sensing based image reconstruction methods were incorporated to improve image resolution with reduced imaging time. Both computer simulation study and phantom imaging study proved that the proposed method outperformed the conventional phase-sorting method in motion range assessment with superior image quality

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COLO-R Ectal Endoscopic Full-thickness Resection (EFTR) with the over-the-scope device (FTRD®): A multicenter Italian experience

Endoscopic full-thickness resection(EFTR) with FTRD® in colo-rectum may be useful for several indications.The aim was to assess its efficacy and safety.

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Mycophenolate mofetil treatment in patients with autoimmune hepatitis failing standard therapy with prednisolone and azathioprine

Data on rescue treatment of autoimmune hepatitis in patients that fail standard treatment are sparse.

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The Burden of Digestive Disease across Europe: Facts and Policies.

The past decade has witnessed a significant increase in the incidence of GI diseases across Europe. There are clear differences in outcomes for patients in Europe based on geographical and economic differences, and there is a worrying inequality in the provision of healthcare across the continent. Recent demographic studies have highlighted the heavy burden of GI disease across Europe. There is increasing demand for endoscopic procedures which are becoming increasingly more complex and demand further expertise and training.

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Cost analysis and outcome of endoscopic submucosal dissection for colorectal lesions in an outpatient setting

Endoscopic submucosal dissection (ESD), a minimally invasive treatment for early gastrointestinal (GI) cancer, is considered challenging and risky in the colorectum. As such, most patients undergoing ESD are hospitalized due to the perceived increased risk of adverse events. The aim of this study was to compare the costs, safety and efficacy of colorectal-ESD in an outpatient vs inpatient setting in a tertiary level center.

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The Importance of Delabeling β-Lactam Allergy in Children

An 11-month-old, previously healthy male infant was diagnosed by his primary care provider with acute otitis media after 2 days of fever and irritability. He was prescribed amoxicillin 90 mg/kg/day for a 10-day course. This course of antibiotics was his first. On day 4, the child developed maculopapular exanthem approximately 5 hours after a dose of amoxicillin (Figure 1; available at www.jpeds.com). There was no associated angioedema, vomiting, diarrhea, or respiratory symptoms. There was no associated high fever, skin sloughing, joint swelling, hematuria, or other systemic symptoms.

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Prevalence and Treatment of Depression, Anxiety, and Conduct Problems in US Children

To use the latest data to estimate the prevalence and correlates of currently diagnosed depression, anxiety problems, and behavioral or conduct problems among children, and the receipt of related mental health treatment.

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A Preterm Infant with Abdominal Distension and Bloody Stools

A 40-day-old, preterm, female infant was referred to a neonatal intensive care unit secondary to abdominal distension and bloody stools. The infant, born by vaginal delivery at 336/7 weeks of gestation secondary to maternal preeclampsia, weighed 1950 g. Both Caucasian parents had no chronic medical conditions. At the referring facility, she had 3 episodes (on days 3, 6, and 20 of life) of abdominal distension and bloody gastric aspirates and/or hematochezia. Enteral feeding (expressed breast milk), initiated at age 3 days, was stopped at multiple intervals.

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Congenital Epulides—Spontaneous Regression

A healthy 2-month-old girl was referred to a pediatric dental clinic for evaluation of 2 intra-oral masses, present since birth. One mass was localized on the maxillary alveolar process, the other on the mandible (Figure 1). Both had sessile bases and were firm on palpation. Neither of the masses was mobile, and manipulation did not appear to cause pain or discomfort. Mouth closure was normal. The parents reported that the lesions had not changed in size since birth. It was determined that these masses posed no immediate aspiration risk and there was no interference with breathing or feeding.

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Did You Examine the Parents?

A 5-month-old boy presented to the Emergency Department with a febrile illness and respiratory distress of 4 days' duration. He had been delivered at term by cesarean delivery performed due to polyhydramnios, reduced fetal movements, and nonprogression of labor. After birth, he had frequent feeding problems, pooling of secretions, choking after feeds, and repeated hospitalizations for pneumonia. Examination revealed normal head circumference, bitemporal hollowing, bifacial and bulbar weakness, inverted V-shaped upper lip, generalized hypotonia, reduced spontaneous antigravity movements, and hyporeflexia.

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Recurrent Vulvar Ulcers and “Cradle Cap” in a 2-Year-Old

A 2-year-old white female with recurrent methicillin-resistant Staphylococcus aureus otitis media and persistent "cradle cap" was referred for dermatologic evaluation of recurrent, painful vaginal ulcers present for 10 months. The symptoms began with severe vaginal pain during urination and diaper changes. She subsequently developed painful, solitary, bilateral ulcers on the labia majora that responded minimally to topical menthol-zinc oxide and clobetasol. Observation without treatment led to resolution of the ulcers within 3 weeks; the ulcers reoccurred 2 months later.

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Case 31-2018: A 37-Year-Old Man with a Self-Inflicted Gunshot Wound

Presentation of Case. Dr. Jordan P. Bloom (Surgery): A 37-year-old man was admitted to the surgical intensive care unit (ICU) of this hospital because of a self-inflicted gunshot wound. The patient had been in his usual state of health until 2 days before admission. That evening, while he was at…

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A Candida auris Outbreak and Its Control in an Intensive Care Setting

Candida auris is an emerging, multidrug-resistant pathogen that has recently been associated with outbreaks worldwide, often in intensive care units (ICUs). It was described in 2009 after isolation from the ear canal of a Japanese patient and was reported as a cause of bloodstream infection in…

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Antibody-Mediated Rejection of Solid-Organ Allografts

End-stage organ diseases are responsible for millions of deaths worldwide each year. Organ transplantation has become the treatment of choice, but despite the 120,000 new organ transplantations performed each year, only 1 million persons worldwide have functioning solid-organ transplants because of…

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Bilateral Vestibular Schwannomas in Neurofibromatosis Type 2

A 32-year-old man presented to the neurosurgery clinic with mild balance difficulties and hearing loss in the left ear. He had a family history of neurofibromatosis type 2 and a diagnosis of tumors in the right and left internal acoustic canals. He had not previously had symptoms related to the…

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Neuroblastoma and Histone Demethylation

Neuroblastoma is a childhood cancer of the sympathetic nervous system, with a propensity for widespread metastasis and aggressive clinical behavior. For patients with so-called high-risk disease (typically patients 18 months of age or older who present with metastatic disease), standard therapy is…

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Allogeneic BK Virus–Specific T Cells for Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating infection of the central nervous system caused by reactivation of the JC polyomavirus that occurs in the context of defective cellular immunity. Common underlying conditions that are associated with JC virus infection include…

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Fatal Encephalitic Borna Disease Virus 1 in Solid-Organ Transplant Recipients

To the Editor: Borna disease virus 1 (BoDV-1; species Mammalian 1 orthobornavirus) causes progressive meningoencephalitis, mainly in horses and sheep. Evidence of BoDV-1 infection in humans is limited. However, after the identification of a bornavirus transmitted by exotic pet squirrels — the…

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Woltman’s Sign of Hypothyroidism

Figure 1.

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