An Overview of Near Infrared Fluorescent Cholangiography with Indocyanine Green during Cholecystectomy

Laparoscopic cholecystectomy (LC) is one of the most common surgical procedures performed globally but continues to carry to an unacceptably high risk of iatrogenic bile duct injury (BDI). In recent years several centres have proposed Near Infrared Fluorescent Cholangiography (NIRFC) with Indocyanine Green (ICG) as a potential method of dynamic intraoperative extra hepatic bile duct mapping. We provide an overview of the current problem of BDI during laparoscopic cholecystectomy including the incidence, aetiology and medico legal ramifications. We also provide a short summary of the enduring argument for and against routine intraoperative cholangiogram (IOC) and we discuss the new technology of NIRFC with ICG in detail. We provide an informative summary of the small number of highly heterogeneous clinical trials of NIRFC with ICG currently available and briefly discuss limitations of the technology

Trends in management of proximal humerus fractures in the United States : 1998-2009

Proximal humerus fractures (PHFs) are common but they do not have a standard of treatment. Historically, surgeons have opted for closed reduction percutaneous pinning (CRPP) or open reduction internal fixation (ORIF) for simple fractures and hemiarthroplasty (HA) for more complex fractures. ORIF has become increasingly popular because of its expanded utility with locking plates. The use of CRPP has declined and been limited to simple fractures with recent literature showing unexpectedly higher complication rates. Reverse total shoulder arthroplasty (RTSA) was introduced in the U.S. in 2003 and has been used to treat complicated shoulder problems such as cuff tear arthropathy, revision, and 4-part PHFs. The aim of this study was to analyze the shifting emphasis between operative modalities for displaced PHFs. We hypothesized that the rate of total shoulder arthroplasty (TSA) would increase after the introduction of RTSA

Multiple Application Propfan Study (MAPS): Advanced tactical transport

This study was conducted to ascertain potential benefits of a propfan propulsion system application to a blended wing/body military tactical transport. Based on a design cruise Mach no. of 0.75 for the design mission, the results indicate a significant advantage in various figures of merit for the propfan over those of a comparable technology turbofan. Although the propfan has a 1.6 percent greater takeoff gross weight, its life cycle cost is 5.3 percent smaller, partly because of a 27 percent smaller specific fuel consumption. When employed on alternate missions, the propfan configuration offers significantly improved flexibility and capability: an increase in sea level penetration distance of more than 100 percent, or in time-on-station of 24 percent, or in deployment payload of 38 percent

Bioproduction of Linalool From Paper Mill Waste

A key challenge in chemicals biomanufacturing is the maintenance of stable, highly productive microbial strains to enable cost-effective fermentation at scale. A “cookie-cutter” approach to microbial engineering is often used to optimize host stability and productivity. This can involve identifying potential limitations in strain characteristics followed by attempts to systematically optimize production strains by targeted engineering. Such targeted approaches however do not always lead to the desired traits. Here, we demonstrate both ‘hit and miss’ outcomes of targeted approaches in attempts to generate a stable Escherichia coli strain for the bioproduction of the monoterpenoid linalool, a fragrance molecule of industrial interest. First, we stabilized linalool production strains by eliminating repetitive sequences responsible for excision of pathway components in plasmid constructs that encode the pathway for linalool production. These optimized pathway constructs were then integrated within the genome of E. coli in three parts to eliminate a need for antibiotics to maintain linalool production. Additional strategies were also employed including: reduction in cytotoxicity of linalool by adaptive laboratory evolution and modification or homologous gene replacement of key bottleneck enzymes GPPS/LinS. Our study highlights that a major factor influencing linalool titres in E. coli is the stability of the genetic construct against excision or similar recombination events. Other factors, such as decreasing linalool cytotoxicity and changing pathway genes, did not lead to improvements in the stability or titres obtained. With the objective of reducing fermentation costs at scale, the use of minimal base medium containing paper mill wastewater secondary paper fiber as sole carbon source was also investigated. This involved simultaneous saccharification and fermentation using either supplemental cellulase blends or by co-expressing secretable cellulases in E. coli containing the stabilized linalool production pathway. Combined, this study has demonstrated a stable method for linalool production using an abundant and low-cost feedstock and improved production strains, providing an important proof-of-concept for chemicals production from paper mill waste streams. For scaled production, optimization will be required, using more holistic approaches that involve further rounds of microbial engineering and fermentation process development

The effect of Liver Transplantation on the quality of life of the recipient's main caregiver - a systematic review

Introduction: Liver transplantation (LT) is a transformative, life-saving procedure with life-long sequale for patients and their caregivers. The impact of LT on the patient's main caregiver can be underestimated. We carried out a systematic review of the impact of LT on the Health Related Quality of Life (HRQL) of LT patients’ main caregivers. Methods: We searched 13 medical databases from 1996 to 2015. We included studies with HRQL data on caregivers of patients following LT then quality assessed and narratively synthesized the findings from these studies. Results: Of 7076 initial hits, only five studies fell within the scope of this study. In general, they showed caregiver burden persisted in the early period following LT. One study showed improvements, however the other four showed caregiver's levels of stress, anxiety and depression, remained similar or got worse post-LT and remained above that of the normal population. It was suggested that HRQL of the patient impacted on the caregiver and vice versa and may be linked to patient outcomes. No data was available investigating which groups were at particular risk of low HRQL following LT or if any interventions could improve this. Conclusion: The current information about LT caregivers’ needs and factors that impact on their HRQL are not adequately defined. Large studies are needed to examine the effects of LT on the patients’ family and caregivers in order to understand the importance of caregiver support to maximise outcomes of LT for the patient and their caregivers

Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial

OBJECTIVE: Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin. Local tolerability and treatment satisfaction were also assessed. DESIGN: 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). METHODS: Male or female patients aged 18-79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan ( = 61) or once-daily Norditropin ( = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). RESULTS: Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin ( = 0.0171). CONCLUSIONS: In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin

Vitamin D deficiency in traumatic brain injury and its relationship with severity of injury and quality of life: a prospective, observational study

This single-centre prospective observational study aims to describe the prevalence of vitamin D deficiency (VDD) in the traumatic brain injury (TBI) population and identify any relationship between vitamin D and severity of head injury or quality of life. 124 TBI patients had serum vitamin D (25-OHD) levels measured at the local post-TBI endocrine screening clinic over 20 months. Quality of Life after Brain Injury (QOLIBRI) questionnaires were completed by the patient concurrently. A multivariate regressional analysis was performed, controlling for age, season, ethnicity, time since injury, TBI severity and gender. 34% (n=42) of the cohort were vitamin D deficient (25-OHD <25nmol/L) with a further 23% (n=29) having insufficient levels (25-OHD 25-50nmol/L). Vitamin D was significantly lower in severe TBI compared to mild TBI (n=95, p=0.03, CI 95% -23.60 to -1.21, mean effect size 12.40 nmol/L). There was a trend for self-reported quality of life to be better in patients with optimum vitamin D levels compared to patients with deficient vitamin D levels, controlling for severity of injury (n=81, p=0.05, CI 95% -0.07 to 21.27). This is the first study to identify a significant relationship between vitamin D levels and severity of head injury. Clinicians should actively screen for and treat VDD in head injured patients to reduce the risk of further morbidity such as osteomalacia and cardiovascular disease. Future research should establish the natural history of vitamin D levels following TBI to identify at which stage VDD develops and whether vitamin D replacement could have a beneficial effect on recovery and quality of life

Cost-utility analysis of operative versus non-operative treatment for colorectal liver metastases

Abstract Background Surgical resection of colorectal liver metastases (CRLMs) is the standard of care when possible, although this strategy has not been compared with non-operative interventions in controlled trials. Although survival outcomes are clear, the cost-effectiveness of surgery is not. This study aimed to estimate the cost-effectiveness of resection for CRLMs compared with non-operative treatment (palliative care including chemotherapy). Methods Operative and non-operative cohorts were identified from a prospectively maintained database. Patients in the operative cohort had a minimum of 10 years of follow-up. A model-based cost–utility analysis was conducted to quantify the mean cost and quality-adjusted life-years (QALYs) over a lifetime time horizon. The analysis was conducted from a healthcare provider perspective (UK National Health Service) in a secondary care (hospital) setting. Results Median survival was 41 and 21 months in the operative and non-operative cohorts respectively (P &amp;lt; 0·001). The operative strategy dominated non-operative treatments, being less costly (€22 200 versus €32 800) and more effective (4·017 versus 1·111 QALYs gained). The results of extensive sensitivity analysis showed that the operative strategy dominated non-operative treatment in every scenario. Conclusion Operative treatment of CRLMs yields greater survival than non-operative treatment, and is both more effective and less costly. </jats:sec

The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance.

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines