Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies

Abstract

Biofabrication techniques have endeavored to improve the regeneration of the peripheral nervous system (PNS), but nothing has surpassed the performance of current clinical practices. However, these current approaches have intrinsic limitations that compromise patient care. The "gold standard" autograft provides the best outcomes but requires suitable donor material, while implantable hollow nerve guide conduits (NGCs) can only repair small nerve defects. This review places emphasis on approaches that create structural cues within a hollow NGC lumen in order to match or exceed the regenerative performance of the autograft. An overview of the PNS and nerve regeneration is provided. This is followed by an assessment of reported devices, divided into three major categories: isotropic hydrogel fillers, acting as unstructured interluminal support for regenerating nerves; fibrous interluminal fillers, presenting neurites with topographical guidance within the lumen; and patterned interluminal scaffolds, providing 3D support for nerve growth via structures that mimic native PNS tissue. Also presented is a critical framework to evaluate the impact of reported outcomes. While a universal and versatile nerve repair strategy remains elusive, outlined here is a roadmap of past, present, and emerging fabrication techniques to inform and motivate new developments in the field of peripheral nerve regeneration.

Biofabrication strategies have made significant steps toward overcoming the clinical challenges of peripheral nerve repair. Many activities have focused on emulating the structural features of native nerve tissue which promote nerve regeneration, resulting in the development of a variety of fabrication techniques. This review discusses the most relevant approaches, highlights their biomimetic character, and assesses performance in achieving nerve repair.

http://ift.tt/2mTLvzY

Magnetic Macroporous Hydrogels as a Novel Approach for Perfused Stem Cell Culture in 3D Scaffolds via Contactless Motion Control

Abstract

There is an urgent need for 3D cell culture systems that avoid the oversimplifications and artifacts of conventional culture in 2D. However, 3D culture within the cavities of porous biomaterials or large 3D structures harboring high cell numbers is limited by the needs to nurture cells and to remove growth-limiting metabolites. To overcome the diffusion-limited transport of such soluble factors in 3D culture, mixing can be improved by pumping, stirring or shaking, but this in turn can lead to other problems. Using pumps typically requires custom-made accessories that are not compatible with conventional cell culture disposables, thus interfering with cell production processes. Stirring or shaking allows little control over movement of scaffolds in media. To overcome these limitations, magnetic, macroporous hydrogels that can be moved or positioned within media in conventional cell culture tubes in a contactless manner are presented. The cytocompatibility of the developed biomaterial and the applied magnetic fields are verified for human hematopoietic stem and progenitor cells (HSPCs). The potential of this technique for perfusing 3D cultures is demonstrated in a proof-of-principle study that shows that controlled contactless movement of cell-laden magnetic hydrogels in culture media can mimic the natural influence of differently perfused environments on HSPCs.

Perfused 3D scaffolds promise to overcome the limitations of 2D culture systems. An innovative 3D magnetic hydrogel system that greatly improves the diffusion-limited nutrient transport in state-of-the-art approaches by moving the hydrogel contactless in conventional cell culture tubes is presented. The engineered system is verified with hematopoietic progenitor cell culture and shows the impact of perfused environments on cell behavior.

http://ift.tt/2Bdrfhf

A study of hematologic and biochemical profile in female dromedary camels during the breeding and non-breeding seasons

Abstract

Dromedary camel is a seasonal breeder, with the maximum breeding activity during winter and spring and minimum activity occurring in summer and autumn in female camels of southwest Iran. This study was performed to investigate hematological and serum biochemical changes during breeding and non-breeding seasons in female camels, raised in Khouzestan Province. Blood samples were collected from 32 apparently healthy female dromedary camels during December to March as breeding period and from June to October as non-breeding period. Complete blood counts and serum biochemical parameters were analyzed. The results revealed a significant rise in erythrocyte markers including RBC, Hb, HCT, and MCHC in peak breeding season. Serum creatinine concentration in the breeding season was significantly higher than the non-breeding one. Cholesterol and triglyceride levels were both significantly increased in camels sampled during their maximum breeding time. There was also a significant elevation in protein concentration in the mentioned group (P < 0.05). Phosphorus and magnesium levels, in contrast to calcium, were higher in the breeding period (P < 0.05). The activity of serum enzymes comprising LDH, GGT, and ALT was significantly increased in the breeding season (P < 0.05). In spite of that, total bilirubin concentration declined in the same period. It can be concluded that reproductive status can make a considerable alteration in hematologic and biochemical profile in female dromedary camel which must be considered when interpreting laboratory data obtained from this species.

http://ift.tt/2mVt7XL

Anatomical Study of the So-called “Retromolar Gland”: Distinguishing Normal Anatomy from Oral Cavity Pathology

Abstract

Introduction: The minor salivary glands in the retromolar trigone have rarely been studied. The aim of this study was to better define the anatomy of the minor salivary glands in the retromolar trigone and establish the relationships between these and adjacent structures. Materials and Methods: The gland in the retromolar trigone was exposed and its relationships to surrounding structures were observed on twenty cadaveric sides. Results: The boundaries of the gland included the superior pharyngeal constrictor muscle, the tendon of the buccinator muscle, and loose connective tissue. The gland was not continuous with the pterygomandibular or parapharyngeal spaces, but loose connective tissue was present between glands in the retromolar trigone and the medial pterygoid muscle. Conclusions: To our knowledge, this is the first study to describe the detailed anatomy of the minor salivary gland in the retromolar trigone. We suggest that the minor salivary gland in the retromolar trigone should be named the "retromolar gland." This article is protected by copyright. All rights reserved.

http://ift.tt/2mTJZOi

Tibolone and risk of gynecological hormone sensitive cancer

Abstract

Risk of ovarian cancer with hormone therapy is associated with use of both unopposed estrogen therapy and combined estrogen-progestin therapy, whereas for endometrial cancer addition of continuous progestin decreases the estrogen induced increased risk. Less is known about risk with use of tibolone; a synthetic steroid with estrogenic, progestagenic, and androgenic properties. We assessed these associations in a prospective cohort study, including all Danish women 50–79 years of age and followed 1995–2009. National Danish Registers captured individually updated exposure information, cancer cases including histology and confounding factors. Poisson regression analyses provided multiple adjusted incidence rate ratio's (IRR).

More than 900,000 women were followed for 9.8 years on average; 4,513 were diagnosed with ovarian cancer and 6,202 with endometrial cancer.

Compared to women never on postmenopausal hormone therapy, current users of tibolone had an increased IRR for ovarian cancer (1.42(95% confidence interval [CI], 1.01-2.00) and serous ovarian tumors (2.21(95%CI 1.48-3.32)). The risk increased with duration of use, particularly for serous ovarian tumors.

Compared to never users, the IRR of endometrial cancer was 3.56(95%CI 2.94-4.32) among current users of tibolone and 3.80(95%CI 3.08–4.69) of Type 1 endometrial cancer. The steepest risk increase with duration of use was for Type I tumors.

In conclusion, tibolone is associated with increased risk for ovarian and endometrial cancer overall; and particular the risk of serous ovarian tumors and Type 1 endometrial cancer. Because the associations are stronger with increasing durations of use - and for hormone sensitive tumors -the results seem indicative of causality. This article is protected by copyright. All rights reserved.

http://ift.tt/2mUf04J

Progestin-Only and Combined Oral Contraceptives and Receptor-Defined Premenopausal Breast Cancer Risk: The Norwegian Women and Cancer Study

Abstract

Receptor-defined subtypes of breast cancer represent distinct cancer types and have differences in risk factors. Whether the two main hormonal forms of oral contraceptives (OCs); i.e. progestin-only (POC) and combined oral contraceptives (COC), are differentially associated with these subtypes are not well known. The aim of this study was to assess the effect of POC and COC use on hormone receptor-defined breast cancer risk in premenopausal women in a prospective population-based cohort – The Norwegian Women and Cancer study (NOWAC). Information on OC use was collected from 74,862 premenopausal women at baseline. Updated information was applied when follow-up information became available. Multiple imputation was performed to handle missing data, and multivariable Cox regression models were used to calculate hazard ratios (HR) for breast cancer. 1245 incident invasive breast cancer cases occurred. POC use ≥ five years was associated with ER+ (HR = 1.59, 95% CI 1.09 – 2.32, p_trend = 0.03) and ER+/PR+ cancer (HR = 1.63, 95% CI 1.07 – 2.48, p_trend = 0.05), and was not associated with ER- (p_{heterogeneity} = 0.36) or ER-/PR- (p_{heterogeneity} = 0.49) cancer. COC use was associated with ER- and ER-/PR- cancer, but did not increase risk of ER+ and ER+/PR+ cancer. Current COC use gave different estimates for ER/PR-defined subtypes (p_{heterogeneity} = 0.04). This is the first study to show significant associations between POC use and hormone receptor-positive breast cancer. The lack of power to distinguish effects of POC use on subtype development calls for the need of larger studies to confirm our finding. This article is protected by copyright. All rights reserved.

http://ift.tt/2Beyu8D

Quality of life assumptions determine which cervical cancer screening strategies are cost-effective

Abstract

Quality adjusted life years are used in cost-effectiveness analyses (CEAs). To calculate QALYs, a 'utility' (0-1) is used for each health state induced or prevented by the intervention. We aimed to estimate the impact of quality-of-life (QoL) assumptions (utilities and durations of health states) on CEAs of cervical cancer screening. To do so, twelve alternative sets of utility assumptions were retrieved from published cervical cancer screening CEAs. Two additional sets were based on empirical QoL data that were integrally obtained through two different measures (SF-6D and EQ-5D) from eight groups of women (total n= 3,087), from invitation for screening to diagnosis with cervical cancer. Per utility set we calculated the number of quality-adjusted days lost (QADL) for each relevant health state in cervical cancer screening, by multiplying the study-specific assumed disutilities (i.e. 1-utility) with study-specific durations of the loss in QoL, resulting in 14 'QADL-sets'. With microsimulation model MISCAN we calculated cost-effectiveness of 342 alternative screening programs (varying in primary screening test [Human Papillomavirus (HPV) versus cytology], starting ages, and screening interval) for each of the 14 QADL-sets. Utilities used in CEAs appeared to differ largely. We found that ten QADL-sets from the literature resulted in HPV and two in cytology as preferred primary test. The SF-6D empirical QADL-set resulted in cytology and the EQ-5D one in HPV as preferred primary test. In conclusion, assumed utilities and health state durations determine cost-effectiveness of cervical cancer screening. Also, the measure used to empirically assess utilities can be crucial for CEA conclusions. This article is protected by copyright. All rights reserved.

http://ift.tt/2mUVfKg

Physicians’ perspective on the clinical meaningfulness of inflammatory bowel disease trial results: an International Organization for the Study of Inflammatory Bowel Disease (IOIBD) survey

Summary

Background

Several novel compounds are being developed for inflammatory bowel diseases (IBD). In addition, biosimilar drugs are being approved. An increasing number of head-to-head, superiority and non-inferiority trials in patients with IBD are expected in the future. The clinical relevance of the magnitude of the effect size is often debated.

Aim

To better understand physicians' perspectives on the clinical meaningfulness of IBD trial results.

Methods

We conducted an online survey among all IOIBD (International Organization for the Study of Inflammatory Bowel Diseases) members, asking their opinion on the clinical relevance of the results of IBD trials.

Results

Forty-six IOIBD members responded to the survey (52.3%). In biologic-naïve ulcerative colitis (UC) and Crohn's disease (CD) patients, most of the participants considered a 15% difference with placebo for clinical remission and endoscopic remission to be clinically relevant.

In head-to-head trials, most of participants considerer a 10% difference between groups for clinical remission and endoscopic remission to be clinically relevant. Half of respondents considered 10% to be an adequate margin in non-inferiority trials. In bioequivalence studies, most of the participants considered adequate a ± 5% difference between a biosimilar and the originator for pharmacokinetic parameters, efficacy, safety and immunogenicity. Regarding safety, the difference between two drugs considered clinically relevant varied from 1% to 5%, depending on the type of adverse event.

Conclusions

This is the first survey exploring how physicians perceive IBD trial results, providing an estimation of the magnitude of the difference between treatment arms that may directly influence clinical practice.

http://ift.tt/2mToddM

Postmarketing cases of eluxadoline-associated pancreatitis in patients with or without a gallbladder

Summary

Background

Cases of pancreatitis were identified in the eluxadoline clinical development program, reflected in initial product labelling, and the subject of postmarketing reports.

Aim

To analyse postmarketing cases of eluxadoline-associated pancreatitis.

Methods

We retrospectively analysed all US adverse event reports of pancreatitis associated with eluxadoline reported to the FDA Adverse Event Reporting System (FAERS) database from May 27, 2015 through February 15, 2017.

Results

The analysis included 119 cases of pancreatitis associated with eluxadoline; one resulted in death and 75 in hospitalisation. Sixty-seven cases reported the presence (n = 12) or absence (n = 55) of the patient's gallbladder. The eluxadoline dose received in the 55 cases of patients without gallbladders was 75 mg (n = 43), 100 mg (n = 5), or not reported (n = 7). Of the 119 cases, 37 reported the patient did not abuse alcohol and 82 did not report the alcohol abuse status. The single fatal case occurred in a patient without a gallbladder who received eluxadoline 75 mg and did not abuse alcohol. Forty-seven cases reported development of pancreatitis within the first or second dose of eluxadoline initiation. The median time to onset for the development of pancreatitis (n = 83) was 1 day, ranging from 1 to 56 days of continued use of eluxadoline.

Conclusion

The FAERS cases suggest that patients with or without a gallbladder receiving eluxadoline are at risk for the development of pancreatitis. However, patients without a gallbladder, despite receiving the recommended lower dose of eluxadoline 75 mg and screening for alcohol abuse, appear to be overrepresented among patients who developed eluxadoline-associated pancreatitis.

http://ift.tt/2BdnloB

The effectiveness and safety of ledipasvir plus sofosbuvir in adolescents with chronic hepatitis C virus genotype 4 infection: a real-world experience

Summary

Background

The combination of ledipasvir plus sofosbuvir was recently approved for treatment of adolescent (12-17 years) HCV genotype 1, 4, 5 & 6 patients. However, few clinical trials have been performed in genotype 1 patients.

Aim

To investigate the effectiveness and safety of ledipasvir plus sofosbuvir in chronic HCV adolescent patients with genotype 4 in the real world.

Methods

This prospective multicentre (six centres) open-label study included 144 adolescent chronic HCV patients with genotype 4 (mean age 14 ± 2, 69% males). All patients received a combination tablet containing 400 mg sofosbuvir and 90 mg ledipasvir once daily for 12 weeks. Laboratory and virological markers were evaluated at baseline, week 4, week 8 and week 12 (EOT), and 12 weeks after end of treatment (SVR12).

Results

SVR12 was observed in 142/144 patients (99%). The relapsers occurred in previous naïve patients (n = 2/128, 2%), while the experienced patients showed 100% SVR12. SVR12 was 98% in F0/F1 patients in comparison to 100% in F2 patients (P = 0.552). No serious side effects were observed, nor was treatment discontinuation or death. Headache was the most common side effect in all patients (20%). In experienced patients, pruritus (31%, P = 0.007), diarrhoea (44%, P < 0.001) and skin rash (19%, P = 0.002) were higher than in naïve patients.

Conclusions

A ledipasvir plus sofosbuvir regimen is well tolerated and effective, and can be used safely in treating adolescent patients with chronic hepatitis C genotype 4.

http://ift.tt/2mToayC

Reduced left ventricular filling following blood volume extraction does not result in compensatory augmentation of cardiac mechanics

Abstract

An acute non-invasive reduction in preload has been shown to augment cardiac mechanics to maintain stroke volume and cardiac output. Such interventions induce concomitant changes in heart rate (HR), whereas blood volume extraction reduces preload without HR changes. Therefore, the purpose of this study was to determine whether a preload reduction in isolation resulted in augmented stroke volume achieved via enhanced cardiac mechanics. Nine healthy volunteers (4 female, age 29 ± 11 years) underwent echocardiography for the assessment of left ventricular (LV) volumes and mechanics in a supine position at baseline and end-extraction following the controlled removal of 25% of total blood volume (1062 ± 342 ml). Arterial blood pressure was monitored continuously by a pressure transducer attached to an indwelling radial artery catheter. HR and total peripheral resistance were unchanged from baseline to end extraction, but systolic blood pressure was reduced (148 to 127 mmHg). LV end diastolic volume (89 to 71 ml) and stroke volume (56 to 37 ml) were significantly reduced from baseline to end extraction; however, there was no change in LV twist, basal or apical rotation. In contrast, LV longitudinal strain (−20 to −17%) and basal circumferential strain (−22 to −19%) were significantly reduced from baseline to end extraction. In conclusion, a preload reduction during blood volume extraction does not result in compensatory changes in stroke volume or cardiac mechanics. Our data suggest that LV strain is dependent on LV filling and consequent geometry whereas LV twist could be mediated by heart rate.

This article is protected by copyright. All rights reserved

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The vaccine adjuvant alum promotes IL-10 production that suppresses Th1 responses

Abstract

The effectiveness of many vaccines licensed for clinical use relates to the induction of neutralising antibodies, facilitated by the inclusion of vaccine adjuvants, particularly alum. However, the ability of alum to preferentially promote humoral rather than cellular, particularly Th1-type responses, is not well understood. We demonstrate that alum activates immunosuppressive mechanisms following vaccination, which limit its capacity to induce Th1 responses. One of the key cytokines limiting excessive immune responses is IL-10. Injection of alum primed draining lymph node cells for enhanced IL-10 secretion ex-vivo. Moreover, at the site of injection, macrophages and dendritic cells were key sources of IL-10 expression. Alum strongly enhanced the transcription and secretion of IL-10 by macrophages and dendritic cells. The absence of IL-10 signalling did not compromise alum-induced cell infiltration into the site of injection, but resulted in enhanced antigen-specific Th1 responses after vaccination. In contrast to its decisive regulatory role in regulating Th1 responses, there was no significant change in antigen-specific IgG1 antibody production following vaccination with alum in IL-10-deficient mice. Overall, these findings indicate that injection of alum promotes IL-10, which can block Th1 responses and may explain the poor efficacy of alum as an adjuvant for inducing protective Th1 immunity.

This article is protected by copyright. All rights reserved

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Report of a human autopsy case in maxillary sinuses augmented using a synthetic bone substitute: Micro-computed tomographic and histologic observations

Abstract

Objective

This study of a human autopsy case aimed to characterize the histologic and micro-computed tomographic results of maxillary sinus augmentation using a synthetic bone substitute and simultaneous implant placement at 6 years.

Material and methods

This report is based on the whole-body donation of a 62-year-old male patient who died due to bladder cancer. Implants had been placed in conjunction with sinus augmentation using a mixture of biphasic calcium phosphate and autogenous bone into both maxillary sinuses 6 years prior to the body donation. The maxillary sinus areas containing implants were gently removed from the cadaver and scanned using high-resolution micro-computed tomography. Samples were sectioned, prepared for undecalcified histologic slides and stained with haematoxylin-eosin.

Results

The augmented volume was observed up to the apex of the implants, which were successfully osseointegrated. Cross-sectional micro-computed tomographic views revealed that the bone-substitute particles were embedded in radiopaque-mineralized tissues showing a trabecular pattern around the implants. The histologic analysis revealed mature lamellar bone surrounding the remaining bone-substitute particles as well as well-organized bone marrow spaces in the augment bone area and around the dental implants.

Conclusion

This human autopsy study histologically confirmed the presence of successful bone formation and long-term volume stability after sinus augmentation using biphasic calcium phosphate and simultaneous implant placement.

http://ift.tt/2EUismw

DSP30 and interleukin-2 as a mitotic stimulant in B-cell disorders including those with a low disease burden

Abstract

Chromosome abnormalities detected during cytogenetic investigations for B-cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B-cell disorders, predominantly in chronic lymphocytic leukaemia (CLL) but also a range of other B-cell malignancies. Here we describe the comparison of two B-cell mitogens, lipopolysaccharide (LPS) and DSP30 combined with IL2 as mitogens in a range of common B-cell disorders excluding CLL. The results showed that DSP30/IL2 was an effective mitogen in mature B-cell disorders, revealing abnormal cytogenetic results in a range of B-cell malignancies. The abnormality rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS). In a number of cases the disease burden was proportionally very low, less than 10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal results. Importantly, we also obtained abnormal conventional cytogenetics results in 3 bone marrow cases in which immunophenotyping showed an absence of an abnormal B-cell clone. In these cases the cytogenetics results correlated with the provisional diagnosis and altered their staging level. The use of DSP30 and IL2 is recommended for use in many B-cell malignancies as an effective mitogen and their use has been shown to enable successful culture of the malignant clone, even at very low levels of disease. This article is protected by copyright. All rights reserved.

http://ift.tt/2mS46MW

The Danish Medical Birth Register

Abstract

The Danish Medical Birth Register was established in 1973. It is a key component of the Danish health information system. The register enables monitoring of the health of pregnant women and their offspring, it provides data for quality assessment of the perinatal care in Denmark, and it is used extensively for research. The register underwent major changes in construction and content in 1997, and new variables have been added during the last 20 years. The aim was to provide an updated description of the register focusing on structure, content, and coverage since 1997. The register includes data on all births in Denmark and comprises primarily of data from the Danish National Patient Registry supplemented with forms on home deliveries and stillbirths. It contains information on maternal age provided by the Civil Registration System. Information on pre-pregnancy body mass index and smoking in first trimester is collected in early pregnancy (first antenatal visit). The individual-level data can be linked to other Danish health registers such as the National Patient Registry and the Danish National Prescription Registry. The register informs several other registers/databases such as the Danish Twin Registry and the Danish Fetal Medicine Database. Aggregated data can be publicly accessed on the Danish Health Data Authority web page (www.esundhed.dk/sundhedsregistre/MFR). Researchers can obtain access to individual-level pseudo-anonymised data via servers at Statistics Denmark and the Danish Health Data Authority.

http://ift.tt/2Bc5TRs

Stent-assisted coil embolization on down-the-barrel view with spring-shaped microcatheter in patient with M1 ultrawide necked circumferential aneurysm

Herein, we describe a technique for stent-assisted coil embolization with a spring-shaped microcatheter in a patient with an M1 ultrawide-necked circumferential aneurysm in the middle cerebral artery (MCA). A 49-year-old man was referred for treatment of an incidentally detected M1 large-circumference aneurysm on magnetic resonance angiography. Subsequent digital subtraction angiography revealed an 18.2x16.5 mm ultrawide-necked circumferential aneurysm on the distal M1 portion of the left MCA, and we planned stent-assisted coil embolization using a spring-shaped microcatheter. After we deployed the stent, we performed coil embolization under the down-the-barrel view by pulling out the microcatheter little by little. Using this technique, we could fill the coil mass evenly into the aneurysmal sac around the stent. And there were no immediate or delayed complications after the procedure. Stent-assisted coiling using a spring-shaped microcatheter is a useful and safe technique for treating ultrawide-necked circumferential aneurysm or fusiform aneurysms.

http://ift.tt/2Djz3zQ

Moyamoya tipping point: fatal bilateral MCA territory infarction following cocaine abuse

Description  

An adult Caucasian man with a history of polysubstance abuse was found unresponsive by the nursing staff at his rehabilitation centre and intubated by emergency medical services. On examination, he was stuporous, his eyes did not open to stimulation, his pupils were reactive, localised to pain with bilateral upper extremities and demonstrated triple flexion to noxious stimuli in the bilateral lower extremities. Urine toxicology was positive for cocaine metabolites. A CT scan of the head was performed, which showed possible hypodensities in the bilateral temporal lobes. MRI of the brain was performed to further characterise these hypodensities, and it revealed bilateral middle cerebral artery (MCA) infarction and generalised cerebral oedema (figure 1). CT angiogram of the head at this point was performed, which showed narrowing of both MCAs and possible moyamoya pattern on the left (figure 2). This moyamoya-like vascular change was suggested by narrowing of the left MCA and hypervascular lenticulostriate...

http://ift.tt/2DPIyYz

Megaduodenum in a 59-year-old man: a very late postoperative complication after duodenal atresia

Intestinal malformations are common defects of the newborn, treated in experienced centres. Reports on long-term follow-up and associated complications are scarce, possibly leading to misinterpretation of clinical signs and symptoms in adulthood. To prevent treatment errors, it is important that physicians are aware of long-term complications of intestinal malformations.

http://ift.tt/2Di1azw

Retroperitoneal bile leak after laparoscopic cholecystectomy

Bile duct injury (BDI) is a well-recognised complication of laparoscopic cholecystectomy (LC). Following a BDI, bile usually leaks into the peritoneal space and causes biliary peritonitis. This manifests as non-specific abdominal pain and fever occurring several days after the surgery. It can be managed by laparoscopic washout with or without bile duct repair. We present a rare case of retroperitoneal bile leak post-LC. The mechanism of injury here was likely partial avulsion from excessive traction of the cystic duct during intraoperative cholangiogram. Diagnosing retroperitoneal bile leak can be difficult because it is extremely rare and the presenting symptoms can be similar to an intraperitoneal bile leak. A high index of clinical suspicion is required. In cases of suspected bile leak, any mismatch between the exploratory laparoscopic findings and imaging findings should alert surgeons to consider the rare possibility of a retroperitoneal bile leak.

http://ift.tt/2DP09zN

Vanadium allergy following total knee arthroplasty

Allergic reactions to metals following joint arthroplasty represent a rare and poorly understood phenomenon. Much is still unknown regarding the natural history of this complication, and how it can best be prevented and managed. We present a case of a 68-year-old woman who underwent a left total knee arthroplasty for treatment of osteoarthritis. After an initial uneventful postoperative course, she developed a troublesome erythematous rash both around the incision site and over her trunk. Blood testing revealed no evidence of infection and clinically her prosthesis was functioning well. Skin patch testing revealed positive results for vanadium (+) and palladium (+). Her cutaneous symptoms are currently being managed conservatively and have shown a partial response to topical steroids. Revision surgery remains a long-term treatment option should conservative therapy fail; however, it would require a custom-made prosthesis as no standard tibial component is free from vanadium.

http://ift.tt/2Dm69yQ

Role of modified Eloesser flap in the treatment of bronchopleural fistula caused by pulmonary coccidioidomycosis

Description

Coccidioidomycosis is a fungal infection by the Coccidioides genus and is usually caused by inhalation of the spores. Patients with diabetes are more likely to present with severe lung disease, especially cavitary lesions.1 2 We depict the case of a 47-year-old man with uncontrolled type 2 diabetes mellitus who presented with a right pulmonary lung abscess due to coccidioidomycosis and underwent a right thoracotomy with partial right upper lobe resection. Intraoperatively the pleura was found to be thickened, and the upper lobe had multiple adhesions and was perforated, creating a purulent bronchopleural fistula. He developed recurrent right-sided empyema due to the fistula and an attempt at a second thoracotomy was unsuccessful. After placement of three failed endobronchial valves, he ultimately had a tunnelled pleural catheter placed. Two weeks later the patient began draining frank pus from the site and a modified Eloesser flap...

http://ift.tt/2DO4hzX

Continuous subcutaneous levetiracetam in end-of-life care

Seizures constitute a determining aspect in quality of life and are frequently challenging in palliative care—a field where treatment has yet to be standardised. Levetiracetam—a new generation anticonvulsant—has proved efficacy both through oral, as well as intravenous administration in the general population. This case reports on the use of continuous subcutaneous levetiracetam to effectively control seizures in a terminally ill patient without patent oral route.

http://ift.tt/2DhCHdt

Unusual skin mass (primary cutaneous mucinous carcinoma)

Primary mucinous carcinoma of the skin is a rare malignant tumour of sweat gland origin. Diagnostic concerns include its deceptively benign appearance in some cases and the difficulty in differentiating it from secondary mucinous carcinoma of skin metastasising from a primary source elsewhere. A case of a 75-year-old man is reported who presented with a slowly growing painless mass near the lateral canthus of the right eye for about 2 years. Clinically, a diagnosis of basal cell carcinoma was made whereas histopathology revealed mucinous carcinoma of the skin. The primary source of the tumour could not be found on detailed physical examination and laboratory investigations. Immunohistochemistry, performed later, was consistent with primary cutaneous mucinous carcinoma.

http://ift.tt/2DPfWia

An adult case with shigellosis-associated encephalopathy

A 45-year-old man was presented at the emergency department with altered neurological status and a 1-day history of diarrhoea and fever. The patient's sexual history revealed multiple male partners. As bacterial meningitis or viral encephalitis was suspected, treatment was started accordingly. Cerebrospinal fluid investigations only showed a slight increase of leucocytes, and microbiological studies remained negative. Stool culture revealed Shigella flexneri, after which Shigella-associated encephalopathy was suspected. The patient recovered quickly with antibiotic treatment. The incidence of Shigella infections in the Western world is rising due to sexual transmission among men who have sex with men. Shigella-induced encephalopathy is a notorious complication among children with a severe form known as the Ekiri syndrome, though rarely seen in adults. This is the second report of encephalopathy in an adult with S. flexneri enteric infection.

http://ift.tt/2DkESgf

Angiodysplastic Sturge Weber syndrome

Description

A 3-year-old boy presented with global developmental delay, abnormal craniofacial growth and left focal seizures since infancy. He was the first child of a non-consanguineous couple with unremarkable perinatal period. Family history was non-contributory. On examination, he had macrocephaly (head circumference 55 cm, >3 z-score), extensive port-wine stain distributed bilaterally over the face and the trunk, cloverleaf-shaped skull with facial distortion (figure 1A), marked gingival hyperplasia with dental malocclusion (figure 1B), bilateral blue sclera with tortuous engorged veins, brisk muscle stretch reflexes, left hemiparesis and bilateral Babinski's sign. The rest of the systemic examination was unremarkable. A clinical diagnosis of angiodysplastic variant of Sturge Weber syndrome (SWS) with extensive bilateral facial and truncal port-wine stain, glaucoma and focal epilepsy was considered. CT of the brain revealed right-sided subcortical tram-track calcification and concordant parenchymal volume loss (figure 1C). MRI of the brain showed right-sided...

http://ift.tt/2DL5oQZ

Intravitreal bevacizumab for postviral fever retinitis: a novel approach for early resolution of macular oedema

Severe macular oedema causing marked loss of vision is seen in cases of retinitis developing postviral fever. The use of antivascular endothelial growth factor agents for macular oedema and submacular fluid secondary to viral retinitis has not been studied or well established in the past. We report a case series of two patients of postviral retinitis with severe macular oedema resistant to steroid therapy, treated with intravitreal bevacizumab. The patients showed significant symptomatic improvement in the visual acuity. The retinitis lesions resolved slowly and macular oedema regressed. Bevacizumab appears to be a safe and useful agent to manage macular oedema subsequent to postviral retinitis. An early resolution of macular oedema helps in the preservation of visual acuity which left untreated can cause severe visual loss.

http://ift.tt/2DhCDdJ

Abnormal deep dorsal vein resulting in veno-occlusive erectile dysfunction

A 59-year-old man with a 6-year history of erectile dysfunction presented to the andrology outpatient clinic. Multimodality assessment with ultrasound, MRI venography and fluoroscopic venography demonstrated an aberrant emissary vein arising from the corporal bodies causing venogenic erectile dysfunction. Selective coil embolisation of the collateral vein resulted in an almost immediate and sustained improvement in his erections.

http://ift.tt/2DP04ft

Anterior choroidal artery infarction

Description 

A 38-year-old male patient with a history of hypertension presented with left hemiplegia, hemianaesthesia and hemianopia. MRI of the brain showed anterior choroidal artery (AchA) territory infarct (figure 1). MRI brain angiography and 2D echo were normal. Serum fasting lipid profile, sugar levels, thyroid studies, serum homocysteine levels and antinuclear antibody (ANA), double-stranded deoxyribonucleic acid (DsDNA) and antiphospholipid antibody (APLA) were negative. Trans-oesophageal echocardiography and Holter monitoring were normal. Workup for sickle cell anaemia was negative.

Figure 1

Axial diffusion weighted MRI shows restricted diffusion in (A,B) right lateral thalamus, posterior limb of internal capsule; hippocampal gyrus and uncus and (C) paraventricular corona radiata and uncus. (D) Coronal T2 image showing involvement of same areas.

The territory of AchA is shown in figure 2.1

Figure 2

(A) Anterior choroidal artery originates from internal carotid artery...

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Sacral bone cyst treatment resulting in paraplegia

Description

A 50-year-old man with a stage 1 solitary right sacral plasmacytoma complained of a sharp, burning lower back pain with radiation into his right lower extremity which worsened with movement. He had initially undergone localised radiation therapy, but the pain did not resolve. Postradiation CT-guided biopsy showed persistence of malignant plasma cells, and he then underwent seven cycles of VRD (dexamethasone, lenalidomide and bortezomib) chemotherapy. After chemotherapy, an 18-fluorodeoxyglucose-positron emission tomography/CT scan showed a new area of uptake in the right sacral ala near the initial plasmacytoma. A subsequent CT-guided biopsy was non-diagnostic, and repeat imaging at the time of presentation showed no interval growth. The lesion was believed to be a residual cyst with inflammatory changes from radiotherapy. Examination revealed no neurological deficits. The patient's pain was thought to be secondary to the cyst (figure 1) and was not relieved with physical therapy, duloxetine...

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Proportion of women presenters at medical grand rounds at major academic centres in Canada: a retrospective observational study

Objective

To assess the proportion of women who presented research or medical grand rounds at five major academic hospitals in Canada.

Design

A cross-sectional study.

Setting

Five major university-affiliated hospitals in Toronto and Calgary.

Results

Overall, at all sites and types of academic rounds, there were an average of 17% fewer women presenting than men (P<0.001). There were an average of 32% and 21% more men presenting at the city-wide grand rounds in cities A and B, respectively (P<0.001, P=0.002). There were more male speakers at four out of five types of rounds. The proportion of women presenting on average was proportional to the Canadian workforce, but on average, below the proportion of female residents and medical students (median ratio 1.1, 0.7 and 0.8, respectively).

Conclusion

Our study demonstrated a lower proportion of females in an important outlet for academic recognition and role modelling. This provides a possible contributing factor to the under-representation of women in academic medicine and an area that can be systematically targeted to promote equity.

http://ift.tt/2mNGxUE

Oxidative status of growing West African dwarf goat kids fed diets containing different nutrient density

Abstract

Nutritional manipulation is the best option against parasitic infection in ruminants, as it has no residual effect on the animal. Nutrition improves the resilience and resistance of the infected animals and eliminates the resultant clinical anaemia. Twenty-four growing intensively raised West African dwarf (WAD) goats (10.2 + 0.78) were used to assess the effect of incremental levels of protein and energy on the performance characteristics and oxidative status of the WAD goats. The animals were individually housed and allotted to diets containing varying levels of crude protein and energy levels: high-energy high-protein (HH), medium-energy medium-protein (MM) and low-energy low-protein (LL) diets in a completely randomised design. Data were collected for changes in weight gain, haematogical and serum constituents, oxidative stress biomarkers and faecal egg count. Higher levels of energy and protein in the diets increased (P < 0.05) metabolic weight gain (kgBW^0.75) and average daily gain (g/day). Increased levels of crude protein and energy significantly (P < 0.05) increased packed cell volume, haemoglobin concentration and red blood cell count of the goats. Thiol concentration was increased (P < 0.05) with increased level of protein and energy in the diets. The observed reductions in egg per gram of the faeces were similar among the treatment groups. Therefore, increased levels of protein and energy in the diets improve the dry matter intake and daily weight gain with increased erythrocyte count and antioxidant status (through increased thiol concentration) in goats fed MM and HH diets.

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Issue Information

No abstract is available for this article.

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Después de 3 años en semFYC: Grupo de Trabajo Salud Basada en las Emociones ¿Quiénes somos? ¿Qué hacemos? ¿Cuál es nuestra intención?

Javier Bris Pertíñez, Marisa Valiente, Alfonso García Viejo
Aten Primaria.2018;50:1-2

Texto completo - PDF

http://ift.tt/2mVcpre

Big data y seguridad de la información

Joan Gené Badia, Pedro Gallo de Puelles, Itziar de Lecuona
Aten Primaria.2018;50:3-5

Texto completo - PDF

http://ift.tt/2BdivHN

Adecuación del tratamiento de la osteoporosis en prevención primaria. Estudio cuantitativo y cualitativo

Cristina Vedia Urgell, Mireia Massot Mesquida, Roser Valles Fernandez, Juan Antonio Garcia Vicente, Alicia Franzi Siso, Laura Muñoz Ortiz, Laia Vilaró Jaques, Maite Bosch Peligero
Aten Primaria.2018;50:6-15

Resumen - Texto completo - PDF

http://ift.tt/2mToCNe

Utilidad de los estudios serológicos en los centros de Atención Primaria para el diagnóstico precoz de la enfermedad de Lyme

María Esther Vázquez-López, Gonzalo Fernández, Pablo Díaz, Carolina Díez-Morrondo, Robustiano Pego-Reigosa, Amparo Coira-Nieto
Aten Primaria.2018;50:16-22

Resumen - Texto completo - PDF

http://ift.tt/2Beeu62

La dependencia: efectos en la salud familiar

M. Eugenia Estrada Fernández, Ana I. Gil Lacruz, Marta Gil Lacruz, Antonio Viñas López
Aten Primaria.2018;50:23-34

Resumen - Texto completo - PDF

http://ift.tt/2mTKwA1

Actitud clínica ante la dislipemia en pacientes con elevado riesgo cardiovascular en España. Estudio ALMA

Xavier Pintó, Ferran Trias Vilagut, Joan Rius Taruella, Esther Mairal Sallán
Aten Primaria.2018;50:35-43

Resumen - Texto completo - PDF

http://ift.tt/2BdGTcs

Sensibilidad antibiótica de Staphylococcus aureus y Streptococcus pneumoniae en personas portadoras nasales sanas en atención primaria en el área de Barcelona

Carles Llor, Albert Boada, Mariona Pons-Vigués, Elisabet Grenzner, Rosa Juvé, Jesús Almeda
Aten Primaria.2018;50:44-52

Resumen - Texto completo - PDF

http://ift.tt/2mU5jn8

Descenso de la incidencia de la varicela en la Comunidad de Madrid tras la vacunación infantil universal. Años 2001-2015

Luis García Comas, Pello Latasa Zamalloa, Guadalupe Alemán Vega, María Ordobás Gavín, Araceli Arce Arnáez, Inmaculada Rodero Garduño, Alicia Estirado Gómez, Ester Insúa Marisquerena
Aten Primaria.2018;50:53-9

Resumen - Texto completo - PDF

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Anemia en la enfermedad renal crónica: protocolo de estudio, manejo y derivación a Nefrología

Aleix Cases, M. Isabel Egocheaga, Salvador Tranche, Vicente Pallarés, Raquel Ojeda, José Luis Górriz, José María Portolés
Aten Primaria.2018;50:60-4

Resumen - Texto completo - PDF

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El concepto de funcionalidad como ejemplo del cambio del modelo nosológico tradicional

Nicolás Martínez-Velilla, Cristina Ibarrola Guillén, Ana Fernández Navascués, Javier Lafita Tejedor
Aten Primaria.2018;50:65-6

Texto completo - PDF

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Las mujeres siguen siendo las principales cuidadoras de pacientes dependientes

Anna Peña, Angeles Machado, Teresa Mur, Margarita Saiz
Aten Primaria.2018;50:66-7

Texto completo - PDF

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Estudio prospectivo de la incidencia de eventos cardiovasculares en adultos jóvenes y su relación con el síndrome metabólico

Matilde González-Solanellas, Meritxell Puig Esmandia, Pablo Rodriguez Blanco, Edurne Zabaleta-del-Olmo
Aten Primaria.2018;50:67-9

Texto completo - PDF

http://ift.tt/2Be1MEv

Fibromialgia y empatía: un camino hacia el bienestar

Patricia Roth Damas, Mónica Portillo Santamaría, Blanca Folch Marín, Vicente Palop Larrea
Aten Primaria.2018;50:69-70

Texto completo - PDF

http://ift.tt/2mTBnaq

Risk stratification for febrile neutropenia in patients with testicular germ cell tumors

Abstract

The aim of this study was to detect risk factors for febrile neutropenia (FN) in patients with testicular germ cell tumors (TGCT). In this retrospective cohort study at the Medical University of Graz, we included 413 consecutive TGCT patients who received adjuvant or curative treatment with cisplatin-based chemotherapy. FN occurred in 70 (16.9%) of 413 patients. In univariable logistic regression, higher age (odds ratio (OR) per 5 years = 1.17, 95% CI: 1.02–1.35, P = 0.022), reduced performance status (PS) (OR = 2.73, 1.47–5.06, P = 0.001), seminomatous histology (OR = 2.19, 1.26–3.78, P = 0.005), poor IGCCCG risk class (OR = 4.20, 1.71–10.33, P = 0.002), and prior radiotherapy (pRTX) (OR = 8.98, 2.09–38.61, P = 0.003) were associated with a higher risk of FN. In multivariable analysis adjusting for age and risk classification, only poor PS (OR = 2.06, 1.05–4.03, P = 0.035), seminomatous histology (OR = 2.08, 1.01–4.26, P = 0.047), and pRTX (OR = 7.31, 1.61–33.17, P = 0.010) prevailed. In the subgroup of seminoma patients (n = 104), only pRTX predicted for FN risk (OR = 5.60, 1.24–25.34, P = 0.025). Five of eight seminoma patients with pRTX developed FN (63%), as compared to 22 FN cases (23%) in the 96 seminoma patients without pRTX (P = 0.027). The eight seminoma patients who received pRTX had significantly lower pre-chemo white blood counts (4.7 vs. 6.5 G/L), neutrophil counts (3.2 vs. 4.3 G/L), and platelet counts (185 vs. 272 G/L) than patients without pRTX (all P < 0.0001). TGCT patients with a reduced performance status or who had been previously treated with radiotherapy have an increased risk for neutropenic fever during chemotherapy.

The aim of this study was to detect prognostic factors for febrile neutropenia (FN) in patients with testicular germ cell tumors. We identified (1) higher age, (2) poor performance status, (3) poor IGCCCG risk classification, and (4) prior radiotherapy in the seminoma subpopulation as risk factors for FN in patients with testicular cancer.

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Extending the utility of the WHO recommended assay for direct detection of enteroviruses from clinical specimen for resolving poliovirus co-infection

In a polio-free world there might be reduced funding for poliovirus surveillance. There is therefore the need to ensure that enterovirologist globally, especially those outside the global polio laboratory netw...

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Characterization of highly virulent multidrug resistant Vibrio cholerae isolated from a large cholera outbreak in Ghana

The purpose of this study was to investigate the virulent factors of Vibrio cholerae which caused an unprecedented large cholera outbreak in Ghana in 2014 and progressed into 2015, affected 28,975 people with 243...

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A synergic effect between CYP2C19*2, CYP2C19*3 loss-of-function and CYP2C19*17 gain-of-function alleles is associated with Clopidogrel resistance among Moroccan Acute Coronary Syndromes patients

The main objective of our study was to investigate the association of CYP2C19*2 and CYP2C19*3 loss-of-function and CYP2C19*17 gain-of-function variants of CYP2C19 gene with Clopidogrel resistance in a sample o...

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Primary explant culture and collagen I substrate enhances corneal endothelial cell morphology

Corneal endothelial cell (CEC) isolation and harvest aim to produce engineered grafts to solve donor corneal tissue shortage. To yield high amounts of CEC maintaining morphological and molecular characteristic...

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Drug Promotion Practices: A review

Abstract

Over the years, the pharmaceutical industry has been at the forefront of research and innovation in drug discovery and development. The process of drug discovery extending from pre-clinical studies to multi-centric clinical trials and post-marketing phase is a costly affair running into billions of dollars. On the flip side, not all investigational molecules clear the trial phases and get approved; which puts pressure on the manufacturers to maximise the profit from approved drugs. It is in this key area, the practice of drug promotion plays its role. WHO defines drug promotion as "all informational and persuasive activities by manufacturers and distributors, the effect of which is to influence the prescription, supply, purchase or use of medicinal drugs". With its humble intent of creating awareness among healthcare professionals and updating their knowledge on recent advances in treatment options, drug promotion has been an important tool, but gradually it has evolved to embrace aggressive marketing strategies and sometimes unethical business and scientific practices where the need for profit-making eclipses commitment to patient care and scientific exploration. In this review, we will go through the evolution of drug promotion practices, the various types, its merits and demerits, the influence of drug promotion on physician prescribing behaviour, the role of regulatory bodies, unethical promotional practices and finally summarize with future directions.

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The host response in critically ill sepsis patients on statin therapy: a prospective observational study

Statins can exert pleiotropic anti-inflammatory, vascular protective and anticoagulant effects, which in theory could improve the dysregulated host response during sepsis. We aimed to determine the association...

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Stool cultures at the ICU: get rid of it!

Stool cultures for Campylobacter, Salmonella and Shigella and/or Yersinia spp. are frequently ordered in critically ill patients with diarrhea. The aim of this study is to analyze the diagnostic yield in a large ...

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Aortic dysfunction in metabolic syndrome mediated by perivascular adipose tissue TNFα and NOX2 dependent pathway

Abstract

Aims

Perivascular adipose tissue (PVAT) is recognized for its vaso-active effects, however it's unclear how Metabolic Syndrome impact thoracic-aorta (t)PVAT and the subsequent effect on functional and structural aortic stiffness.

Methods & Results

Thoracic aorta and tPVAT were removed from 16–17 week old lean (LZR, n = 16) and obese Zucker (OZR, n = 16) rats. OZR presented with aortic endothelial dysfunction, assessed by wire-myography, and increased aortic stiffness, assessed by elastic modulus. OZR-tPVAT exudate further exacerbated the endothelial dysfunction reducing nitric oxide and endothelial dependent relaxation (P < 0.05). Additionally, OZR-tPVAT exudate had increased MMP9 activity (P < 0.05) and further increased elastic modulus of the aorta following 72-hours of coculture (P < 0.05). We found the observed aortic dysfunction caused by OZR-tPVAT was mediated through increased production and release of TNFα (P < 0.01), which was dependent on tPVAT NADPH-oxidase 2 (NOX2) activity. OZR-tPVAT ROS and subsequent aortic dysfunction was inhibited by TNFα neutralization and/or inhibition of NOX2. Additionally, we found OZR-tPVAT had reduced activity of the 20S proteasome's active sites (P < 0.05) and reduced superoxide dismutase activity (P < 0.01).

Conclusion

Metabolic syndrome causes tPVAT dysfunction through interplay between TNFα and NOX2 leading to tPVAT mediated aortic stiffness by activation of aortic ROS and increased MMP9 activity.

This article is protected by copyright. All rights reserved

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Medical management of brain metastases and leptomeningeal disease in patients with breast carcinoma

Future Oncology, Ahead of Print.


http://ift.tt/2EWh5Ut

Inherited forms of bladder cancer: a review of lynch syndrome and other inherited conditions

Future Oncology, Ahead of Print.


http://ift.tt/2DuwwWE

Minimally invasive adrenal surgery: virtue or vice?

Future Oncology, Ahead of Print.


http://ift.tt/2EWgX7r

Ovarian tissue cryopreservation in young females through the Oncofertility Consortium's National Physicians Cooperative

Future Oncology, Ahead of Print.


http://ift.tt/2DrEU9w

Tuning CRISPR-Cas9 Gene Drives in Saccharomyces cerevisiae

Control of biological populations is an ongoing challenge in many fields including agriculture, biodiversity, ecological preservation, pest control, and the spread of disease. In some cases, such as insects that harbor human pathogens (e.g. malaria), elimination or reduction of a small number of species would have a dramatic impact across the globe. Given the recent discovery and development of the CRISPR/Cas9 gene editing technology, a unique arrangement of this system-a nuclease based "gene drive"-allows for the Super-Mendelian spread and forced propagation of a genetic element through a population. Recent studies have demonstrated the ability of a gene drive to rapidly spread within and nearly eliminate insect populations in a laboratory setting. While there are still ongoing technical challenges to design of a more optimal gene drive to be used in wild populations, there are still serious ecological and ethical concerns surrounding the nature of this powerful biological agent. Here, we use budding yeast as a safe and fully-contained model system to explore mechanisms that might allow for programmed regulation of gene drive activity. We describe four conserved features of all CRISPR-based drives and demonstrate the ability of each drive component-Cas9 protein level, sgRNA identity, Cas9 nucleocytoplasmic shuttling, and novel Cas9-Cas9 tandem fusions-to modulate drive activity within a population.

http://ift.tt/2DvAnmI

CNS Metastases Needn't Rule Out Trial Inclusion [News in Brief]

Guidelines aim to open more drug studies to patients with central nervous system tumors, increase efficacy data.

http://ift.tt/2DnA7Xr

Phase I dose-escalation study of copanlisib in combination with gemcitabine or cisplatin plus gemcitabine in patients with advanced cancer

Phase I dose-escalation study of copanlisib in combination with gemcitabine or cisplatin plus gemcitabine in patients with advanced cancer

Phase I dose-escalation study of copanlisib in combination with gemcitabine or cisplatin plus gemcitabine in patients with advanced cancer, Published online: 18 January 2018; doi:10.1038/bjc.2017.428

Phase I dose-escalation study of copanlisib in combination with gemcitabine or cisplatin plus gemcitabine in patients with advanced cancer

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H1/pHGFK1 nanoparticles exert anti-tumoural and radiosensitising effects by inhibition of MET in glioblastoma

H1/pHGFK1 nanoparticles exert anti-tumoural and radiosensitising effects by inhibition of MET in glioblastoma

H1/pHGFK1 nanoparticles exert anti-tumoural and radiosensitising effects by inhibition of MET in glioblastoma, Published online: 18 January 2018; doi:10.1038/bjc.2017.461

H1/pHGFK1 nanoparticles exert anti-tumoural and radiosensitising effects by inhibition of MET in glioblastoma

http://ift.tt/2DubEPi

Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by upregulating RIG-I in head and neck squamous cell carcinoma

Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by upregulating RIG-I in head and neck squamous cell carcinoma

Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by upregulating RIG-I in head and neck squamous cell carcinoma, Published online: 18 January 2018; doi:10.1038/bjc.2017.442

Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by upregulating RIG-I in head and neck squamous cell carcinoma

http://ift.tt/2EUheYo

Which patients are not included in the English Cancer Waiting Times monitoring dataset, 2009–2013? Implications for use of the data in research

Which patients are not included in the English Cancer Waiting Times monitoring dataset, 2009–2013? Implications for use of the data in research

Which patients are not included in the English Cancer Waiting Times monitoring dataset, 2009–2013? Implications for use of the data in research, Published online: 18 January 2018; doi:10.1038/bjc.2017.452

Which patients are not included in the English Cancer Waiting Times monitoring dataset, 2009–2013? Implications for use of the data in research

http://ift.tt/2DubKGE

Robot-assisted radical prostatectomy vs laparoscopic and open retropubic radical prostatectomy: functional outcomes 18 months after diagnosis from a national cohort study in England

Robot-assisted radical prostatectomy vs laparoscopic and open retropubic radical prostatectomy: functional outcomes 18 months after diagnosis from a national cohort study in England

Robot-assisted radical prostatectomy <i>vs</i> laparoscopic and open retropubic radical prostatectomy: functional outcomes 18 months after diagnosis from a national cohort study in England, Published online: 18 January 2018; doi:10.1038/bjc.2017.454

Robot-assisted radical prostatectomy vs laparoscopic and open retropubic radical prostatectomy: functional outcomes 18 months after diagnosis from a national cohort study in England

http://ift.tt/2EWquLH

CART targeting of solid tumors: More pieces to the puzzle

CART-based targeting of solid tumors remains a considerable and worthwhile challenge in the field of immunotherapy. The role of chemotherapy to target stroma and enhance CAR cell anti-tumor function, expansion and persistence is still unresolved

http://ift.tt/2Be3Fkq

Mutation Burden Predicts Anti-PD-1 Response [News in Brief]

Study of multiple cancer types finds correlation between response and mutation number.

http://ift.tt/2mNoaza

Effects of yoga interventions practiced in heated and thermoneutral conditions on endothelium-dependent vasodilation: The Bikram yoga heart study

Abstract

We have previously documented improvements in endothelium-dependent vasodilation with a Bikram (hot) yoga intervention in middle-aged adults. Presently, the effect of environmental temperature in hot yoga on endothelial function is unknown.

Purpose

The purpose of this investigation was to determine the effects of Bikram yoga interventions performed in the heated and thermoneutral conditions on endothelium-dependent vasodilation.

Methods

Fifty-two sedentary but apparently healthy adults aged 40–60 years were randomly assigned to one of three groups: Bikram yoga practiced at 40.5°C (n = 19), Bikram yoga practiced at 23°C (n = 14), or sedentary time-control (n = 19). The yoga interventions consisted of 90-minute Bikram yoga classes 3 times a week for 12 weeks. Endothelium-dependent vasodilation was measured noninvasively using brachial artery flow-mediated dilation (FMD).

Results

Body fat percentage determined via dual energy x-ray absorptiometry was significantly lower in the hot yoga group after the intervention than in the thermoneutral yoga and control conditions. Brachial artery FMD increased (P < 0.05) in the thermoneutral yoga group and tended to increase in the hot yoga group (P = 0.056). No changes occurred in the control group. There were no significant differences in FMD change scores between groups.

Conclusions

Bikram yoga practiced in thermoneutral conditions improved endothelium-dependent vasodilation in healthy, middle-aged adults. These novels findings highlight the effectiveness of hatha yoga postures alone, in the absence of a heated practice environment, in improving vascular health and are of clinical significance given the increased propensity toward heat intolerance in aging adults.

This article is protected by copyright. All rights reserved

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Near-infrared spectroscopy to predict organ failure and outcome in sepsis: the Assessing Risk in Sepsis using a Tissue Oxygen Saturation (ARISTOS) study.

Objectives: Sepsis is acute organ dysfunction in the setting of infection. An accurate diagnosis is important to guide treatment and disposition. Tissue oxygen saturation (StO2) can be estimated noninvasively by near-infrared spectroscopy (NIRS), and may be an indicator of microcirculatory dysfunction in early sepsis. We aimed to determine the utility of StO2 for sepsis recognition and outcome prediction among patients presenting to the emergency department (ED) with infection. Patients and methods: A multicentre, prospective, observational cohort study recruited patients who were being admitted to hospital with infection. StO2 was measured in the ED using a handheld NIRS device, Inspectra 300. Outcomes were sepsis, defined as an increase in sequential organ failure assessment score of at least 2 points within 72 h, and composite in-hospital mortality/ICU admission at least 3 days. Results: A cohort of 323 participants, median age 64 (interquartile range: 47-77) years, was recruited at three Australian hospitals. 143 (44%) fulfilled the criteria for sepsis and 22 (7%) died within 30 days. The mean+/-SD StO2 was 74+/-8% in sepsis and 78+/-7% in nonsepsis (P

http://ift.tt/2mPk3CF

Knowledge, attitudes and practices on Schistosomiasis in sub-Saharan Africa: a systematic review

Schistosomiasis remains a global health problem with an estimated 250 million people in 78 countries infected, of whom 85% live in Sub-Saharan Africa. Preventive chemotherapy remains the key public health stra...

http://ift.tt/2mUZSnX

Intracisternal tuberculoma: a refractory type of tuberculoma indicating surgical intervention

Central nervous system (CNS) tuberculoma is a rare disease with severe neurological deficits. This retrospective research is to review the data of patients diagnosed as CNS tuberculoma. Surgeries were performe...

http://ift.tt/2rlHAAI

Incidence of Cancers of the Lower Stomach Increasing among Younger Americans

A type of cancer that occurs in the lower stomach has been increasing among some Americans under the age of 50, even though in the general population the incidence of all stomach cancers has been declining for decades, according to a new study.

http://ift.tt/2DN1Yxe

Robot-assisted radical prostatectomy vs laparoscopic and open retropubic radical prostatectomy: functional outcomes 18 months after diagnosis from a national cohort study in England

http://ift.tt/2mSr9XM

Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by upregulating RIG-I in head and neck squamous cell carcinoma

http://ift.tt/2BbMfVI

Which patients are not included in the English Cancer Waiting Times monitoring dataset, 2009–2013? Implications for use of the data in research

http://ift.tt/2mW8Ktl

Phase I dose-escalation study of copanlisib in combination with gemcitabine or cisplatin plus gemcitabine in patients with advanced cancer

http://ift.tt/2BbM8tg

H1/pHGFK1 nanoparticles exert anti-tumoural and radiosensitising effects by inhibition of MET in glioblastoma

http://ift.tt/2mQVrdO

Levofloxacin in 5 Percent Dextrose 250mg/50mL by AuroMedics: Recall - Presence of Visible Particulate Matter

Audience: Pharmacy, Risk Manager, Infectious Disease [Posted 01/18/2018] ISSUE: AuroMedics Pharma LLC is voluntarily recalling one lot of Levofloxacin in 5% Dextrose Injection 250mg/50mL in a Single-Use flexible container NDC 55150-243-46, Lot...

http://ift.tt/2DnY1Cf

Levofloxacin in 5 Percent Dextrose 250mg/50mL by AuroMedics: Recall - Presence of Visible Particulate Matter

Audience: Pharmacy, Risk Manager, Infectious Disease [Posted 01/18/2018] ISSUE: AuroMedics Pharma LLC is voluntarily recalling one lot of Levofloxacin in 5% Dextrose Injection 250mg/50mL in a Single-Use flexible container NDC 55150-243-46, Lot...

http://ift.tt/2DnY1Cf

Puromycin labeling does not allow protein synthesis to be measured in energy-starved cells

Puromycin labeling does not allow protein synthesis to be measured in energy-starved cells

Puromycin labeling does not allow protein synthesis to be measured in energy-starved cells, Published online: 18 January 2018; doi:10.1038/s41419-017-0056-x

Puromycin labeling does not allow protein synthesis to be measured in energy-starved cells

http://ift.tt/2DMSrpO

Dual suppression of inner and outer mitochondrial membrane functions augments apoptotic responses to oncogenic MAPK inhibition

Dual suppression of inner and outer mitochondrial membrane functions augments apoptotic responses to oncogenic MAPK inhibition

Dual suppression of inner and outer mitochondrial membrane functions augments apoptotic responses to oncogenic MAPK inhibition, Published online: 18 January 2018; doi:10.1038/s41419-017-0044-1

Dual suppression of inner and outer mitochondrial membrane functions augments apoptotic responses to oncogenic MAPK inhibition

http://ift.tt/2DlAj5i

EGFR activation triggers cellular hypertrophy and lysosomal disease in NAGLU-depleted cardiomyoblasts, mimicking the hallmarks of mucopolysaccharidosis IIIB

EGFR activation triggers cellular hypertrophy and lysosomal disease in NAGLU-depleted cardiomyoblasts, mimicking the hallmarks of mucopolysaccharidosis IIIB

EGFR activation triggers cellular hypertrophy and lysosomal disease in NAGLU-depleted cardiomyoblasts, mimicking the hallmarks of mucopolysaccharidosis IIIB, Published online: 18 January 2018; doi:10.1038/s41419-017-0187-0

EGFR activation triggers cellular hypertrophy and lysosomal disease in NAGLU-depleted cardiomyoblasts, mimicking the hallmarks of mucopolysaccharidosis IIIB

http://ift.tt/2DL6o7L

AMP-activated protein kinase agonist N6-(3-hydroxyphenyl)adenosine protects against fulminant hepatitis by suppressing inflammation and apoptosis

AMP-activated protein kinase agonist N₆-(3-hydroxyphenyl)adenosine protects against fulminant hepatitis by suppressing inflammation and apoptosis

AMP-activated protein kinase agonist N₆-(3-hydroxyphenyl)adenosine protects against fulminant hepatitis by suppressing inflammation and apoptosis, Published online: 18 January 2018; doi:10.1038/s41419-017-0118-0

AMP-activated protein kinase agonist N₆-(3-hydroxyphenyl)adenosine protects against fulminant hepatitis by suppressing inflammation and apoptosis

http://ift.tt/2DioNIa

Phosphorylation of ULK1 by AMPK is essential for mouse embryonic stem cell self-renewal and pluripotency

Phosphorylation of ULK1 by AMPK is essential for mouse embryonic stem cell self-renewal and pluripotency

Phosphorylation of ULK1 by AMPK is essential for mouse embryonic stem cell self-renewal and pluripotency, Published online: 18 January 2018; doi:10.1038/s41419-017-0054-z

Phosphorylation of ULK1 by AMPK is essential for mouse embryonic stem cell self-renewal and pluripotency

http://ift.tt/2DMmwG9

First in human study to assess safety, pharmacokinetics and pharmacodynamics of BMS-962212, a direct, reversible, small molecule factor XIa inhibitor in non-Japanese and Japanese healthy subjects

Abstract

Aims

To assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class Factor XIa inhibitor, in Japanese and non-Japanese healthy subjects.

Methods

This was a randomized, placebo-controlled, double-blind, sequential, ascending dose study of 2 hour (Part A) and 5 day (Part B) intravenous (IV) infusions of BMS-962212. Part A used 4 doses (1.5, 4, 10, and 25 mg h^-1) assigned to BMS-962212 or placebo in a 3:1 ratio per dose. Part B used 4 doses (1, 3, 9, and 20 mg h^-1) enrolling Japanese (n = 4 active, n = 1 placebo) and non-Japanese subjects (n = 4 active, n = 1 placebo) per dose. The PK, PD, safety, and tolerability were assessed throughout the study.

Results

BMS-962212 was well tolerated; there were no signs of bleeding and adverse events were mild. In Part A and B, BMS-962212 demonstrated dose-proportionality. The mean half-life in Part A and B ranged from 2.04 - 4.94 h and 6.22 - 8.65 h, respectively. Exposure-dependent changes were observed in the PD parameters, activated partial thromboplastin time (aPTT) and factor XI clotting activity (FXI:C), respectively. The maximum mean aPTT and FXI:C change from baseline at 20 mg h^-1 in Part B was 92% and 90%, respectively. No difference was observed in weight corrected steady-state concentrations, aPTT or FXI:C between Japanese and non-Japanese subjects (p > 0.05).

Conclusion

BMS-962212 has tolerability, PK and PD properties suitable for investigational use as an acute antithrombotic agent in Japanese or non-Japanese subjects.

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Toxicological profile and safety pharmacology of a single dose of fibroblast activation protein-[alpha]-based doxorubicin prodrug: in-vitro and in-vivo evaluation.

Fibroblast activation protein-[alpha] (FAP[alpha]) is a promising tumor-associated target expressed by reactive stromal fibroblasts in tumor tissue. FAP[alpha] has a postprolyl peptidase activity and can specifically cleave N-terminal benzyloxycarbonyl (Z)-blocked peptides, such as the substrate Z-Gly-Pro-AMC. Doxorubicin (DOX) is an effective antitumor drug, but its application is greatly limited by toxic adverse effects owing to poor tumor selectivity. Based on these facts, we previously designed a FAP[alpha]-targeting prodrug of doxorubicin (FTPD) which can be selectively hydrolyzed by FAP[alpha]. FTPD can retain potent antitumor efficacy and has favorable tumor targeting. The present study aimed to further evaluate the toxicological profile and the safety pharmacological property of FTPD in vitro and in vivo. The cytotoxicity assay showed that FTPD displayed markedly lower cytotoxicity to 3T3 cells and HEK-293 cells compared with DOX. In the short-term toxicity study, mice treated with 25 mg/kg of FTPD showed no obvious change in the appearance and general behavior, and no case of mortality was observed within 14 days. Unlike DOX, FTPD exhibited reduced toxicity to heart, liver, kidney, spleen as well as peripheral white blood cells in mice. Moreover, open file test and general pharmacology study were also conducted correspondingly in mice and beagle dogs. It was found that FTPD may not produce significant pharmacological effects on spontaneous locomotor activity and cardiovascular-respiratory system except for a transient decreasing in systolic blood pressure. Taken together, the results of this work suggest that FTPD has more favorable toxicological profile and better drug safety compared with its parent drug DOX. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Safety of BCG Vaccination in Pediatric Liver Transplant Recipients.

No abstract available

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Causes, Preventability, and Cost of Unplanned Rehospitalizations Within 30 Days of Discharge Following Lung Transplantation.

Background: Unplanned rehospitalizations (UR) within 30 days of discharge are common following lung transplantation. It is unknown whether UR represent preventable gaps in care or necessary interventions for complex patients. The objective of this study was to assess the incidence, causes, risk factors, and preventability of UR following initial discharge after lung transplantation. Methods: This was a single-center prospective cohort study. Subjects completed a modified Short Physical Performance Battery (SPPB) to assess frailty at listing and at initial hospital discharge after transplantation and the State-Trait Anxiety Inventory (STAI) at discharge. For each UR a study staff member and the patient's admitting or attending clinician used an ordinal scale (0, not; 1, possibly; 2, definitely preventable) to rate readmission preventability. A total sum score >=2 defined a preventable UR. Results: Of the 90 enrolled patients, 30 (33.3%) had an UR. The single most common reasons were infection (7 (23.3%)) and atrial tachyarrhythmia (5 (16.7%)). Among the 30 UR, 9 (30.0%) were deemed preventable. UR that happened before day 30 were more likely to be considered preventable than those between days 30-90 (30.0% versus 6.2%, p = 0.04). Discharge frailty, defined as SPPB

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Association of Cold Ischemia Time with Acute Renal Transplant Rejection.

Background: Kidney transplantation holds much promise as a treatment of choice for patients with end stage kidney disease. The impact of cold ischemia time (CIT) on acute renal transplant rejection (ARTR) remains to be fully studied in a large cohort of renal transplant patients. Methods: From the Organ Procurement and Transplantation Network database, we analyzed 63,798 deceased donor renal transplants performed between 2000-2010. We assessed the association between CIT and ARTR. We also evaluated the association between recipient age and ARTR. Results: 6,802 patients (11%) were clinically diagnosed with ARTR. Longer CIT was associated with an increased risk of ARTR. After multivariable adjustment, compared with recipients with CIT=24h. The association of CIT and ARTR was more pronounced in patients undergoing re-transplantation: compared with recipients with CIT=24h. Additionally, older age was associated with a decreased risk of ARTR. Compared with recipients 18-29 years old, the relative risk of ARTR was 0.50 (95% confidence interval 0.45, 0.57) in recipients >=60 years old. Longer CIT was also associated with increased risk of death-censored graft loss. Compared with recipients with CIT=24h. Conclusions: Prolonged CIT is associated with an increased risk of ARTR and death-censored graft loss. Older age was associated with a lower risk of ARTR. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Quantifying Frailty in Post Lung Transplant Patients - Can We Predict Who Will Need Readmission?.

No abstract available

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Do Patients Supported With Continuous-Flow Left Ventricular Assist Device (CF-LVADS) Have a Sufficient Risk of Death to Justify a Priority Allocation? A Propensity-score Matched Analysis of Patients Listed In UNOS Status 2.

Background: Outcomes of Continuous Flow Left Ventricular Assist Devices (CF-LVADs) as bridge to transplant have significantly improved. The question has arisen whether patients on CF-LVADs have an increased risk of death on the waiting list as to justify a priority allocation (status 1). The aim of this study was to compare the survival following implantation of CF-LVADs to the survival on the waiting list for patients initially listed in United Network for Organ Sharing (UNOS) status 2. Methods: All patients >18 years listed for Heart Transplantation (HT) in the United States between 2011 and 2013 in UNOS status 2 with no mechanical circulatory support at time of listing were analyzed. Patients were divided into two groups depending on whether they received a new CF-LVAD while listed (CF-LVAD group) or not (NO-LVAD) and were further matched on their Propensity Score (PS) in a 1:2 ratio. Results: Two hundreds and eighty-seven CF-LVAD patients were matched to 574 NO-LVAD patients. Survival after CF-LVAD was significantly lower at 24-month compared to waiting list (75.4+4.4 versus 91.2+8.9%, p

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Race, Risk, and Willingness of End-stage Renal Disease Patients Without Hepatitis C (HCV) to Accept an HCV-infected Kidney Transplant.

Background: Despite effective antiviral treatment, hundreds of kidneys from deceased donors with hepatitis C virus (HCV) are discarded annually. Little is known about the determinants of willingness to accept HCV-infected kidneys among HCV-negative patients. Methods: At 2 centers, 189 patients undergoing initial or reevaluation for transplant made 12 hypothetical decisions about accepting HCV-infected kidneys in which we systematically varied expected HCV cure rate, allograft quality and wait-time for an uninfected kidney. Results: Only 29% of participants would accept an HCV-infected kidney under all scenarios, while 53% accepted some offers and rejected others, and 18% rejected all HCV-infected kidneys. Higher cure rate (OR 3.49, 95% CI 2.33-5.24 for 95% vs. 75% probability of HCV cure), younger donor (OR 2.34, 95% CI 1.91-2.88 for a 20-year-old vs. a 60-year-old hypertensive donor), and longer wait for an uninfected kidney (OR 1.43, 95% CI 1.22-1.67 for 5 vs. 2 years) were associated with greater willingness to accept an HCV-infected kidney. Black race modified the effect of HCV cure rate, such that willingness to accept a kidney increased less for blacks vs. whites as the cure rate improved. Patients >60 years and prior kidney recipients showed greater willingness to accept an HCV-infected organ. Conclusions: Most patients will consider an HCV-infected kidney in some situations. Future trials using HCV-infected kidneys may enhance enrollment by targeting older patients and prior transplant recipients, but centers should anticipate that black patients' acceptance of HCV-infected kidneys will be reduced compared to white patients. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The Authors' Reply.

No abstract available

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Important Facts About Organ Donation and OPO Performance.

No abstract available

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Impact of Willingness to Accept Hepatitis C Seropositive Kidneys Among Hepatitis C RNA-positive Waitlisted Patients.

Background: Kidney transplantation from hepatitis C seropositive (HCV+) donors may benefit hepatitis C RNA-positive (RNA+) candidates, but it is unclear how the willingness to be listed for and accept such kidneys affects waitlist and transplant outcomes. Methods: In a single-center retrospective analysis, HCV+ transplant candidates (N=169) listed from March 2004 to February 2015 were evaluated. All RNA+ candidates were offered the option to be listed for HCV+ donors. RNA- candidates were listed only for HCV- donors. Results: Fifty-seven patients (51% of all RNA+ transplant candidates) willing to accept HCV+ donors were listed for both HCV+ and HCV- donor kidneys. During 6-yr follow up, 43 of 57 (75%) patients accepting HCV+ vs. 19 of 55 (35%) patients not accepting HCV+ received a deceased donor kidney transplant (DDKT, P

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Prospective Assessment of Adenovirus Infection in Pediatric Kidney Transplant Recipients.

Background: Adenovirus infection is associated with graft dysfunction and graft loss in in pediatric cardiac, lung, and liver transplants in prior retrospective studies, but data in pediatric kidney transplant recipients is limited. Methods: We conducted a prospective single-center cohort study of 75 consecutive pediatric kidney transplant recipients who underwent monthly screening for adenovirus viremia and symptom assessment for 2 years posttransplant. Results: Adenovirus viremia was detected in eleven (14.7%) patients at a median onset of 173 (IQR 109-310) days posttransplant; six (8%) had asymptomatic viremia and five (6.7%) had symptomatic disease (2 with hematuria and 3 with an acute febrile respiratory illness). Viremic patients did not differ from nonviremic patients in age, immunosuppression management, or CMV or EBV serostatus, but were more likely to develop CMV viremia during the first 2 years posttransplant. No patient had an increase in creatinine from baseline during the time of adenovirus viremia. In a Cox proportional hazards regression, subclinical adenovirus viremia was not associated with a faster time to a 30% decline in eGFR. Conclusion: Adenovirus infection is common among pediatric kidney transplant recipients and frequently causes symptomatic disease; however, symptoms are often mild and are not associated with a decline in graft function. Routine monitoring for adenovirus viremia in pediatric kidney transplant recipients may not be warranted. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Alpha-fetoprotein Slope >7.5 ng/ml/month Predicts Micro-vascular Invasion and Tumor Recurrence after Liver Transplantation for Hepatocellular Carcinoma.

Background: Rising alpha-fetoprotein (AFP) is a potential marker of worse prognosis after liver transplant (LT) for hepatocellular carcinoma (HCC), but prior studies relied on only two data points and were imprecise in assessing AFP slope. The aim of this study was to examine the association between AFP slope and post-LT HCC recurrence, with AFP slope estimated from multiple data points over time. Methods: Our cohort included 336 patients undergoing LT with MELD exception for HCC within Milan criteria from 2003-2013. Most (98%) had pre-LT loco-regional therapy (LRT). AFP slope was estimated by fitting a regression line to the AFP levels over time. Results: The 1- and 5-year post-LT survival was 94% and 77% and 1- and 5-year recurrence-free probabilities were 95% and 86%, respectively. In univariate analysis, HCC recurrence was significantly associated with microvascular invasion (HR 13.1, pMilan criteria (HR 8.9, p7.5 ng/mL/month (HR 3.9, p=0.005), and female gender (HR 2.3, p=0.01). In multivariable analysis of factors known prior to LT, 3 tumor nodules (HR 7.6, p7.5 (HR 3.0, p=0.03) were significantly associated with HCC recurrence. AFP slope >7.5 was also associated with microvascular invasion (OR 6.8, p=0.008). Conclusions: AFP slope increasing >7.5 ng/mL/month despite LRT is associated with post-LT HCC recurrence and may serve as a surrogate for microvascular invasion. These findings support incorporating changes in the AFP into candidate selection for LT. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Towards Systematic Screening for Persistent Hepatitis E Virus (HEV) Infections in Transplant Patients.

Background: Persistent hepatitis E virus genotype 3 (HEV G3) infections affect solid organ transplant (SOT) recipients and haematopoietic stem cell transplant (HSCT) recipients, but the burden in these cohorts in the UK is unknown. We established an audit to determine the point prevalence of HEV viraemia in SOT and HSCT patients in the UK and compare different testing approaches to inform screening strategies. Methods: Between 5th January and 21st September 2016, 3044 patients undergoing therapeutic drug monitoring at a single transplant centre were screened for HEV RNA in minipools. A total of 2822 patients who could be characterised included 2419 SOT patients, 144 HSCT patients and 259 patients with no available transplant history. HEV RNA-positive samples were characterised by serology and genomic phylogeny. HEV antigen (HEV-Ag) testing was performed on RNA-positive samples, 420 RNA-negative samples and 176 RNA-negative blood donor samples. Results: Nineteen of 2822 patients were viraemic with G3 HEV giving a prevalence of 0.67%. The median alanine aminotransferase (ALT) was significantly higher in the HEV viraemic patients (p

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Ethical Analysis and Policy Recommendations Regarding Domino Liver Transplantation.

Due to the widening gap between supply and demand, patients who need a liver transplant due to metabolic disease may be asked to serve as domino liver donors-to have their native liver transplanted into another candidate. We here analyze the ethical problems surrounding informed consent for the implant and explant procedures in transplant candidates who will serve as domino donors, using the case of a child with maple syrup urine disease. We discuss the need for two distinct consent processes separated in time to ensure that potential domino donors (or their surrogates) give a truly voluntary consent. We propose a Domino Donor Advocate - based on the concept of the Independent Living Donor Advocate to help the patient and/or his or her surrogates consider the risks, benefits and alternatives. Finally, we evaluate the Organ Procurement and Transplantation Network policy regarding "therapeutic organ donation" and propose several modifications to ensure that the decision by the potential domino donor (and/or his or her surrogate) is voluntary and informed. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Superior Hypertension Management in Pediatric Kidney Transplant Patients After Native Nephrectomy.

Background: Native nephrectomy in pediatric kidney transplant recipients is performed for multiple indications. Posttransplant hypertension requiring medical management is common and the effect of native nephrectomy on posttransplant hypertension is poorly studied. Our aim is to evaluate the impact of native nephrectomy on posttransplant hypertension. Methods: 136 consecutive pediatric kidney transplant recipients from 2007 to 2012 were studied at a single institution and divided into 2 groups: no nephrectomy and native nephrectomy (unilateral and bilateral nephrectomy). Antihypertensive medication use was evaluated prior to nephrectomy/transplant, at discharge from transplant and at 1-, 3- and 5-years posttransplant. Results: In a bivariate analysis, nephrectomy was associated with a significant reduction in the percentage of patients requiring antihypertensive medication at the time of discharge (27.3%) and 1 year posttransplant (10.7%) as compared to patients without nephrectomy (71.7%, and 50%, respectively, p

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Adipocytokines in Steatotic Liver Surgery/Transplantation.

Due to the shortage of liver grafts available for transplantation the restrictions on graft quality have been relaxed and marginal grafts such as steatotic livers are now accepted. However, this policy change has not solved the problem, because steatotic liver grafts tolerate ischemia-reperfusion injury poorly. Adipocytokines differentially modulate steatosis, inflammation, and fibrosis and are broadly present in hepatic resections and transplants. The potential use of adipocytokines as biomarkers of the severity of steatosis and liver damage to aid the identification of high-risk steatotic liver donors and to evaluate hepatic injury in the postoperative period are discussed. The hope of finding new therapeutic strategies aimed specifically at protecting steatotic livers undergoing surgery, is a strong impetus for identifying the mechanisms responsible for hepatic failure after major surgical intervention. Hence, the most recently described roles of adipocytokines in steatotic livers subject to ischemia-reperfusion injury are discussed, the conflicting results in the literature are summarized, and reasons are offered as to why strategic pharmacologic control of adipocytokines has yet to yield clinical benefits. Following this, the next steps needed to transfer basic knowledge about adipocytokines into clinical practice in order to protect marginal livers subject to ischemia-reperfusion injury are presented. Recent strategies based on adipocytokine regulation which have shown efficacy in various pathologies, and hold promise for hepatic resection and transplantation are also outlined. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Long Term Outcomes of Pediatric En Bloc Kidney Transplantation: A Single Center Experience with 25 Years Follow Up.

Background: Pediatric en bloc kidneys are considered marginal for transplantation into adults. We aimed to compare the long-term outcomes of pediatric en bloc vs. living donor kidney transplantation. Methods: A retrospective review was undertaken on pediatric en bloc and living donor kidney transplants performed at our center between 1990 and 2001. The outcomes compared between the groups included 25 year graft survival and longitudinal glomerular filtration rate (GFR). Results: There were 72 pediatric en bloc and 75 living donor kidney recipients included in the analysis. Pediatric donors were 16.9 +/- 11.2 months old and weighed 10.7+/-3.8 kg with terminal serum creatinine of 0.50+/-0.45 mg/dl. Living donors were 40.1+/-9.4 years old and serum creatinine was 0.90+/-0.16 mg/dl at the time of donation. En bloc kidney recipients had higher dialysis vintage (23.0 +/- 29.2 vs. 14.3 +/- 14.7 months, p=0.03), and longer cold ischemia time (30.5+/- 9.8 vs. 2.6 +/-0.9 hours, p

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All in The Name of Vanity: An Unanticipated Outcome of Mycobacterium abscessus Infection.

We report a case of refractory skin abscesses caused by Mycobacterium abscessus resulting from cosmetic surgery. A 25-year-old woman developed recurrent cutaneous infection caused by M. abscessus after multiple cosmetic surgeries in the Dominican Republic. Despite of the removal of infected implants, she failed a 20-month treatment with azithromycin, cefoxitin, and amikacin. The patient presented to our institution 28 months after the initial surgeries and approximately 5 months after initiation of her latest antimicrobial regimen of azithromycin, imipenem, and amikacin. Here, she was restarted on cefoxitin 2 g daily, amikacin 750 mg daily, and azithromycin 1000 mg daily. She completed an additional 4 months (a total of 9 months) of therapy with complete clinical resolution. In conclusion, clinical suspicion of M. abscessus infection is essential for the diagnosis. Patient compliance is integral to a successful outcome because the treatment involves prolonged duration, continuous intravenous antibiotics, and multiple potential adverse effects. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Extended Versus Intermittent Infusions of Cefepime for the Treatment of Febrile Neutropenia.

Background: Neutropenic fever is an oncologic emergency treated with [beta]-lactam antibiotics. Previous literature suggests that extended infusions of [beta]-lactam antibiotics may improve clinical outcomes. Currently, there is only 1 previous study investigating the use of extended infusions in this population, which demonstrated a lack of benefit. Objective: The objective of this study was to determine the effectiveness of extended infusions of cefepime compared with intermittent infusions in patients with febrile neutropenia. Methods: A retrospective chart review was completed comparing extended infusions with intermittent infusions of cefepime for febrile neutropenia. Adult patients admitted to a community teaching hospital who incurred febrile neutropenia were included. Results: A total of 166 patients receiving cefepime were included, of which 28 received extended infusions and 138 received intermittent infusions. Overall, baseline characteristics were similar between groups besides receipt of prior chemotherapy, duration of neutropenia, optimal renal dosing, and presence of documented mucositis. In the extended infusion arm, defervescence at 24 hours was more frequent (82% vs 51%, P = 0.002) and median time to defervescence was decreased by 14 hours (10 vs 24 hours, P = 0.02). Furthermore, extended infusions increased the odds of defervescence at 24 hours by 4.28 (95% confidence interval, 1.43-12.75; P = 0.009) and doubled the likelihood of defervescence at any time (hazard ratio, 2.02; 95% confidence interval, 1.23-3.32, P = 0.005). Conclusions: Contrary to prior literature, extended infusions of cefepime significantly decreased the time to defervescence and increased the proportion with defervescence at 24 hours. This suggests that extended infusions of cefepime may be superior to intermittent infusions, but future prospective studies are needed to confirm these findings. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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3 Cases of Systemic Strongyloides in Human Immunodeficiency Virus-Infected Patients.

Strongyloides stercolaris is an intestinal nematode that is endemic in tropical and subtropical areas. In immunocompromised individuals such as individuals with human T-lymphotrophic virus 1 or history of corticosteroid use, Strongyloides (SS) infection can accelerate to hyperinfection or disseminated infection, conditions which are associated with high mortality. Human immunodeficiency virus (HIV) is not considered to be a risk factor for systemic SS infection; however, dozens of cases of HIV patients that have developed SS in the absence of recognized risk factors have been described in the literature. Although the burden of SS in HIV patients is not as high as would be expected if HIV was an equivalent risk factor to human T-lymphotrophic virus 1 or steroid usage, the number of reported cases indicates that there may be a relationship between HIV and SS. We report 3 additional cases of HIV patients with SS infections that presented at a major metropolitan county hospital in Houston, Tex. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

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