"Not all groups come together, but this one just clicks": Ten Tips for Sustaining an Engagement Panel.

In 2017, ten veteran patients with the shared experience of living with chronic pain united to form a Veteran Engagement Panel (VEP) to support the Patient-Centered Outcomes Research Institute® (PCORI®)funded Veterans Pain Care Organizational Improvement Comparative Effectiveness (VOICE) Study. The study, conducted at ten Veterans Affairs (VA) sites, compares two team-based approaches to improve pain management and reduce potential harms of opioid therapy. The panel shares ten best practices for sustaining a successful engagement partnership.

Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent frequently used in elective surgery to reduce blood loss. We recently found it also acts as a potent immune-modulator in patients undergoing cardiac surgery. METHODS: Patients undergoing lower limb surgery were enrolled into the "Tranexamic Acid in Lower Limb Arthroplasty" (TALLAS) pilot study. The cellular immune response was characterised longitudinally pre- and post-operatively using full blood examination (FBE) and comprehensive immune cell phenotyping by flowcytometry. Red blood cells and platelets were determined in the FBE and levels of T cell cytokines and the plasmin-antiplasmin complex determined using ELISA. RESULTS: TXA administration increased the proportion of circulating CD141+ conventional dendritic cells (cDC) on post-operative day (POD) 3. It also reduced the expression of CD83 and TNFR2 on classical monocytes and levels of circulating IL-10 at the end of surgery (EOS) time point, whilst increasing the expression of CCR4 on natural killer (NK) cells at EOS, and reducing TNFR2 on POD-3 on NK cells. Red blood cells and platelets were decreased to a lower extent at POD-1 in the TXA group, representing reduced blood loss. CONCLUSION: In this investigation we have extended our examination on the immunomodulatory effects of TXA in surgery by also characterising the end of surgery time point and including B cells and neutrophils in our immune analysis, elucidating new immunophenotypic changes in phagocytes as well as NK cells. This study enhances our understanding of TXA-mediated effects on the haemostatic and immune response in surgery, validating changes in important functional immune cell subsets in orthopaedic patients.

Doctors' and Nurses' Attitudes of Acupuncture and Acupressure use in Perioperative Care: An Australian National Survey.

BACKGROUND: Acupuncture and acupressure are not being systematically used in the management of postoperative nausea and vomiting and pain, despite being included in the guidelines. AIM: To examine the beliefs, attitudes, and knowledge of Australian nurses/midwives and doctors toward the perioperative use of AA for the management of postoperative nausea and vomiting and pain; to explore the barriers and enablers influencing acupuncture and acupressure integration into hospital setting. METHODS: A mixed-mode approach was undertaken for data collection. An online approach was used to recruit respondents from Australian College of Perioperative Nurses. Three hospitals from three different Australian states were selected via convenience sampling. RESULTS: A total of 421 usable surveys were included in data analysis. The respondents comprised 14.3% doctors and 72.9% nurses/midwives. Overall, 69.4% were female, 85% were trained in Australia with 35% and 51.4% having knowledge or personal exposure to AA in general respectively. Over 60% of the respondents agreed AA should be routinely integrated into perioperative care, and over 80% would recommend AA to their patients if it was provided at their hospital, and, 75% would be willing to receive further education. The three main reported barriers included: perceived lack of scientific evidence (80.9%), unavailability of credentialed provider (77.2%) and lack of reimbursement (60.4%). CONCLUSIONS: Positive attitudes are reported by Australian doctors and nurses toward AA. This is despite of low levels of knowledge or personal exposure to AA. Further studies are required to explore the implementation of barriers and address respondent calls for further education.

Rheological and Solubility Properties of Soy Protein Isolate.

Soy protein isolate (SPI) powders often have poor water solubility, particularly at pH values close to neutral, which is an attribute that is an issue for its incorporation into complex nutritional systems. Therefore, the objective of this study was to improve SPI solubility while maintaining low viscosity. Thus, the intention was to examine the solubility and rheological properties of a commercial SPI powder at pH values of 2.0, 6.9, and 9.0, and determine if heat treatment at acidic or alkaline conditions might positively influence protein solubility, once re-adjusted back to pH 6.9. Adjusting the pH of SPI dispersions from pH 6.9 to 2.0 or 9.0 led to an increase in protein solubility with a concomitant increase in viscosity at 20 °C. Meanwhile, heat treatment at 90 °C significantly improved the solubility at all pH values and resulted in a decrease in viscosity in samples heated at pH 9.0. All SPI dispersions measured under low-amplitude rheological conditions showed elastic-like behaviour (i.e., G' > G″), indicating a weak "gel-like" structure at frequencies less than 10 Hz. In summary, the physical properties of SPI can be manipulated through heat treatment under acidic or alkaline conditions when the protein subunits are dissociated, before re-adjusting to pH 6.9.

Selective brain hypothermia: feasibility and safety study of a novel method in five patients.

BACKGROUND/OBJECTIVE: Reduction of brain temperature remains the most common method of neuroprotection against ischemic injury employed during cardiac surgery. However, cooling delivered via the cardiopulmonary bypass circuit is brief and cooling the body core along with the brain has been associated with a variety of unwanted effects. This study investigated the feasibility and safety of a novel selective brain cooling approach to induce rapid, brain-targeted hypothermia independent of the cardiopulmonary bypass circuit. METHODS: This first-in-human feasibility study enrolled five adults undergoing aortic valve replacement with cardiopulmonary bypass support. During surgery, the NeuroSave system circulated chilled saline within the pharynx and upper esophagus. Brain and body core temperature were continuously monitored. Adverse effects, cardiopulmonary function, and device function were noted. RESULTS: Patient 1 received cooling fluid for an insignificant period, and Patients 2-5 successfully underwent the cooling procedure using the NeuroSave system for 56-89 minutes. Cooling fluid was 12°C for Patients 1-3, 6°C for Patient 4, and 2°C for Patient 5. There were no NeuroSave-related adverse events and no alterations in cardiopulmonary function during NeuroSave use. Brain temperature decreased by 3°C within 15 minutes and remained at least 3.5°C colder than the body core. During a brief episode of hypotension in one patient, the brain cooled an additional 4°C in 2 minutes, briefly reaching 27.4°C. CONCLUSION: The NeuroSave system can induce rapid brain-targeted hypothermia and simultaneously maintain a favorable body-brain temperature gradient, even during hypotension. Further studies are required to evaluate the function of the system during longer periods of use.

The Effect of Chronic Kidney Disease on Mortality with Cardiac Resynchronization Therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves functional status, reduces heart failure hospitalizations, and decreases mortality. Several comorbidities including renal function affect outcomes with CRT. However, moderate to severe chronic kidney disease (CKD) was an exclusion criterion in the large randomized control trials. OBJECTIVE: To evaluate the association of renal function on survival following CRT implantation. METHODS: This was a retrospective analysis of 432 consecutive patients implanted with an implantable cardioverter defibrillator with CRT (CRT-D). The primary end point was defined as death by any cause, and it was determined using hospital records and the U.S. Social Security Death Index. A Kaplan-Meier analysis was performed separating renal dysfunction into renal stage based on glomerular filtration rate. Multivariate analysis was performed to assess the clinical predictors of mortality. RESULTS: Patients were followed for up to 12 years with a mean follow-up time of 4.3 ± 3.2 years. A total of 164 patients (39.3%) died over the course of the study. Patients with normal and mild renal diseases (Stages 1 and 2) had improved survival compared with those with moderate-, severe-, or end-stage (Stages 3-5) renal disease. This effect remained statistically significant after multivariate analysis. The estimated 5-year mortality was 36.3% for stage 1, 33.4% for stage 2, 40.6% for stage 3, and 62.1% for stage 4/5 kidney disease (P = 0.004 by log-rank test). CONCLUSION: CKD is a strong and an independent predictor of long-term mortality among patients undergoing CRT-D implantation.

Personalized oxycodone dosing: using pharmacogenetic testing and clinical pharmacokinetics to reduce toxicity risk and increase effectiveness.

OBJECTIVE: To develop a framework for integrating pharmacogenetics with clinical pharmacokinetics for personalized oxycodone dosing based on a patient's CYP2D6 phenotype. DESIGN: Randomized, crossover, double-blind, placebo-controlled. Subjects were genotyped as CYP2D6 ultra-rapid metabolizer, extensive metabolizer, or poor metabolizer phenotypes. Five subjects from each phenotype were randomly selected for inclusion in our study. SETTING: Studies were performed in silico. SUBJECTS: The subjects were male, age 26 years, height 181.2 cm, and weight 76.3 kg. They were healthy without comorbidities, and their medical examinations were normal. METHODS: The trajectories of phenotype-specific plasma oxycodone concentration-time profiles were analyzed using weighted nonlinear least-squares regression with WinSAAM software. A global two-stage population-based model data analysis procedure was used to analyze the studies. Clinical pharmacokinetics were calculated using the R package cpk, eliminating the need to perform hand-calculations. RESULTS: Our study shows how clinicians can reduce risk and increase effectiveness for oxycodone dosing by (1) determining the patient's likely metabolic response through testing a patient's CYP2D6 phenotype, and (2) calculating clinical pharmacokinetics specific to the patient's CYP2D6 phenotype to design a personalized oxycodone dosing regimen. CONCLUSIONS: Personalized oxycodone dosing is a new tool for a clinician treating chronic pain patients requiring oxycodone. By expressing a patient's CYP2D6 phenotype pharmacokinetically, a clinician (at least theoretically) can improve the safety and efficacy of oxycodone and decrease the risk for iatrogenically induced overdose or death. Pharmacokinomics provides a general framework for the integration of pharmacogenetics with clinical pharmacokinetics into clinical practice for gene-based prescribing.

A qualitative assessment of internal medicine resident perceptions of graduate medical education following implementation of the 2011 ACGME duty hour standards.

BACKGROUND: In 2011, the Accreditation Council of Graduate Medical Education implemented updated guidelines for medical resident duty hours, further limiting continuous work hours for first-year residents. We sought to investigate the impact of these restrictions on graduate medical education among internal medicine residents. METHODS: We conducted eight focus groups with internal medicine residents at the University of Alabama at Birmingham in 06/2012-07/2012. Discussion questions included, "How do you feel the 2011 ACGME work hour restrictions have impacted your graduate medical education?" Transcripts of the focus groups were reviewed and themes identified using a deductive/inductive approach. Participants completed a survey to collect demographic information and future practice plans. RESULTS: Thirty-four residents participated in our focus groups. Five themes emerged: decreased teaching, decreased experiential learning, shift-work mentality, tension between residency classes, and benefits and opportunities. Residents reported that since implementation of the guidelines, teaching was often deferred to complete patient-care tasks. Residents voiced concern that PGY-1 s were not receiving adequate clinical experience and that procedural and clinical reasoning skills are being negatively impacted. PGY-1 s reported being well-rested and having increased time for independent study. CONCLUSIONS: Residents noted a decline in teaching and are concerned with the decrease in "hands-on" clinical education that is inevitably impacted by fewer hours in the hospital, though some benefits were also reported. Future studies are needed to further elucidate the impact of decreased resident work hours on graduate medical education.

Aortic stiffness assessed by global pulse wave velocity in postmenopausal women: an ultrasonographic study.

OBJECTIVE: The first goal of our study was to investigate major determinants of aortic stiffness in postmenopausal women using an echocardiographic method to calculate global pulse wave velocity (PWVg) rather than the less accurate carotid-femoral pulse wave velocity (PWVc). The second goal was to relate PWVg to the absolute risk of major cardiovascular (CV) events estimated by CV risk factors. PATIENTS AND METHODS: Two hundred forty-four consecutive women who presented to our heart station were screened. One hundred twenty-two were postmenopausal, either natural or surgical, whereas 122 were premenopausal. The mean age of the patients was 54 ± 13 years. Individuals were categorized as current smokers, former smokers, or nonsmokers and hypertensive or not. Hypercholesterolemia and diabetes mellitus were defined. Aortic stiffness was assessed by PWVg measured with pulsed Doppler, the interval between the beginning of QRS complex and the foot of the systolic upstroke in the Doppler spectral envelope was calculated at the aortic valve site and at the right common femoral artery. PWVg was calculated between the aortic valve and right common femoral artery by dividing the straight line distance between the two by the transit time. RESULTS: There was a highly significant statistical difference (P < 0.0012) in PWVg between menstruating women and postmenopausal women. Similarly, this difference in PWVg was also noted among the menstruating population (P < 0.0014) when comparing normotensive women and hypertensive women. In postmenopausal women, PWVg was 6.8 m/sec in normotensive women and 7.56 m/sec in hypertensive women (P < 0.007). CONCLUSION: PWVg was increased in postmenopausal women compared with menstruating women. Systemic hypertension has an independent, but additive effect on aortic stiffness assessed by PWVg. Our study supports the usefulness of the assessment of aortic stiffness as a marker of CV disease and to identify subjects at risk at an early age.

Incremental value of live/real time three-dimensional echocardiography in the diagnosis and evaluation of pericardial cyst.

Pericardial cysts are rare anomalies of the pericardium that are usually asymptomatic and followed by two-dimensional (2D) echocardiography. Here we report a large pericardial cyst that could not be measured accurately by 2D echocardiography but three-dimensional (3D) echocardiography enabled measurements of the cyst that correlated well with computed tomography measurements. In addition, 3D echocardiography demonstrated the mono-trabeculated nature of the cyst further suggesting the incremental value of 3D echocardiography in the evaluation of pericardial cysts. The cyst was subsequently resected surgically.

Does the routine echocardiographic exam have a role in the detection and evaluation of cholelithiasis and gallbladder wall thickening?

Cholelithiasis is a very common disease in the United States. Most cases remain asymptomatic but a fraction of these patients can develop serious complications such as cholecystitis which may lead to gallbladder perforation and gallbladder cancer which is much less common. Here, we present three cases of cholelithiasis where transthoracic echocardiography was performed routinely. In each case, echocardiography detected cholelithiasis which prompted three-dimensional (3D) echocardiographic evaluation. Three-dimensional echocardiography allowed for more comprehensive examination of the gallbladder shape, size, and wall thickening and the measurement and composition of the stones in three dimensions, measurement of stone volumes, and minimized shadowing produced by stone calcifications. These cases suggest that routine echocardiography has value in detecting gallstones and that 3D echocardiography has incremental value over two-dimensional echocardiography due to pyramidal data sets which allow sequential slicing through the gallbladder and full gallbladder examination without a technologist who is trained in gallbladder imaging. These pyramidal data sets can be further viewed and cropped by a radiologist specialized in abdominal ultrasound.

Atrial septal occluder device embolization to an iliac artery: a case highlighting the utility of three-dimensional transesophageal echocardiography during percutaneous closure.

Percutaneous closure of secundum atrial defects has become an accepted treatment in part because it is minimally invasive and relatively low risk. Despite recent advances in implantation technique and device improvements, complications occur. Here, we report a case of device embolization during percutaneous repair of an atrial septal defect (ASD) with multiple fenestrations. We highlight the value of using live/real time three-dimensional transesophageal echocardiography to help plan the percutaneous procedure and detect complications.

The ability of live three-dimensional transesophageal echocardiography to evaluate the attachment site of intracardiac tumors.

In this study, a case of a right ventricular myxoma and a case of a right ventricular hemangioma are used to demonstrate the ability of live three-dimensional transesophageal echocardiography (3DTEE) to assess the site of tumor attachment. Because 3DTEE has the ability to visualize desired structures in multiple planes, we defined the attached portion of the tumors and measured the en face view dimensions. In addition, the improved ability of 3DTEE to evaluate tissue characteristics allowed differentiation of the heterogeneous myxoma and highly vascular hemangioma. On the contrary, because two-dimensional (2D) TEE only allows structures to be viewed in a 2D plane, the attachment site can be located but complete delineation and measurement of area is not possible. As surgical options become less invasive, accurate attachment site location and size will become more important to ensure complete excision.

Perioperative antimicrobial decision making: Focused ethnography study in orthopedic and cardiothoracic surgeries in an Australian hospital.

OBJECTIVE: Antimicrobial use in the surgical setting is common and frequently inappropriate. Understanding the behavioral context of antimicrobial use is a critical step to developing stewardship programs. DESIGN: In this study, we employed qualitative methodologies to describe the phenomenon of antimicrobial use in 2 surgical units: orthopedic surgery and cardiothoracic surgery. SETTING: This study was conducted at a public, quaternary, university-affiliated hospital. PARTICIPANTS: Healthcare professionals from the 2 surgical unit teams participated in the study. METHODS: We used focused ethnographic and face-to-face semi-structured interviews to observe antimicrobial decision-making behaviors across the patient's journey from the preadmission clinic to the operating room to the postoperative ward. RESULTS: We identified 4 key themes influencing decision making in the surgical setting. Compartmentalized communication (theme 1) was observed with demarcated roles and defined pathways for communication (theme 2). Antimicrobial decisions in the operating room were driven by the most senior members of the team. These decisions, however, were delegated to more junior members of staff in the ward and clinic environment (theme 3). Throughout the patient's journey, communication with the patient about antimicrobial use was limited (theme 4). CONCLUSIONS: Approaches to decision making in surgery are highly structured. Although this structure appears to facilitate smooth flow of responsibility, more junior members of the staff may be disempowered. In addition, opportunities for shared decision making with patients were limited. Antimicrobial stewardship programs need to recognize the hierarchal structure as well as opportunities to engage the patient in shared decision making.

Prediction of neurological outcome using bispectral index monitoring in patients with severe ischemic-hypoxic brain injury undergoing emergency surgery.

BACKGROUND: Predicting outcome from ischemic-hypoxic brain injury can be difficult in patients rushed to the operating room for time-critical emergency surgery. The authors chose to evaluate the prognostic ability of bispectral index (BIS) in this setting. METHODS: Twenty-five critically ill, unconscious patients with ischemic-hypoxic brain injury undergoing emergency surgery were prospectively studied. Clinical evaluation, laboratory investigations, BIS, and burst suppression ratio were recorded before and during surgery. Neurologic outcome of the patients was measured according to the Glasgow outcome scale at 30 days after injury, with poor neurologic outcome defined as severe disability or death. RESULTS: The incidence of poor neurologic outcome was 68%. Neither clinical judgment (P = 0.40) nor pupillary responses (P = 0.21) were predictive of neurologic outcome after surgery. An abnormal BIS trace was strongly associated with poor neurologic outcome, positive likelihood ratio 6.6 (95% CI 1.7-36.4; exact test P = 0.002). Some BIS values were significantly different when comparing patients with and without poor outcome: c-statistics for the average BIS and maximal electroencephalographic burst-suppression were 0.80 (95% CI 0.62-0.98; P = 0.017) and 0.84 (95% CI 0.68-0.99; P = 0.007), respectively. A normal BIS (P < 0.0005) but not clinical judgment (P = 0.16) could identify a group of patients more likely to survive with a good neurologic outcome. CONCLUSIONS: BIS, when compared with clinical judgment and routine laboratory tests, provides useful information that may identify patients with a good chance of recovery after ischemic-hypoxic brain injury requiring emergency surgery.

Update on the role of paravertebral blocks for thoracic surgery: are they worth it?

PURPOSE OF REVIEW: To consider optimal analgesic strategies for thoracic surgical patients. RECENT FINDINGS: Recent studies have consistently suggested analgesic equivalence between paravertebral and thoracic epidural analgesia. Complications appear to be significantly less common with paravertebral analgesia. SUMMARY: There is good evidence that paravertebral block can provide acceptable pain relief compared with thoracic epidural analgesia for thoracotomy. Important side-effects such as hypotension, urinary retention, nausea, and vomiting appear to be less frequent with paravertebral block than with thoracic epidural analgesia. Paravertebral block is associated with better pulmonary function and fewer pulmonary complications than thoracic epidural analgesia. Importantly, contraindications to thoracic epidural analgesia do not preclude paravertebral block, which can also be safely performed in anesthetized patients without an apparent increased risk of neurological injury. The place of paravertebral block in video-assisted thoracoscopic surgery is less clear.

Impact of Renal Function on Survival After Cardiac Resynchronization Therapy.

Chronic kidney disease (CKD) is associated with worse survival in patients with heart disease including those with implantable devices. Cardiac resynchronization therapy (CRT) can potentially improve renal function. To assess the relation between the change in renal function and survival with CRT, 238 patients undergoing initial CRT with defibrillator implantation between 2002 and 2011 were followed. The primary end point was all-cause mortality. The estimated glomerular filtration rate (eGFR), before implantation and 6 ± 3 months after CRT was calculated. Patients were grouped at baseline into mild (stage I/II) or advanced (stage III/IV) CKD. Patients with end-stage renal disease were excluded. The mean follow-up time was 4.3 years. Multivariate analysis of baseline clinical characteristics showed that only renal function predicted the change in eGFR over the first 6 months of CRT. In the subgroup with mild CKD, eGFR decreased (78.5 ± 17.3 to 67.8 ± 26.8 p <0.001), whereas eGFR did not change in the subgroup with advanced CKD (45.6 ± 11.1 to 46.8 ± 17.0, p = 0.46). Patients with advanced CKD had higher mortality than those with mild CKD (p <0.002). In both subgroups, an increase in eGFR was associated with improved survival (hazard ratio = 0.79, p <0.001). In conclusion, baseline renal function and the subsequent change in eGFR are associated with long-term survival with CRT.

2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways.

In 2016, the American College of Cardiology published the first expert consensus decision pathway (ECDP) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk. Since the publication of that document, additional evidence and perspectives have emerged from randomized clinical trials and other sources, particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD. Most notably, the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial and SPIRE-1 and -2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), assessing evolocumab and bococizumab, respectively, have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients. In addition, further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published. Based on results from these important analyses, the ECDP writing committee judged that it would be desirable to provide a focused update to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities. In the following summary table, changes from the 2016 ECDP to the 2017 ECDP Focused Update are highlighted, and a brief rationale is provided. The content of the full document has been changed accordingly, with more extensive and detailed guidance regarding decision making provided both in the text and in the updated algorithms. Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities on statin therapy for secondary prevention. The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C <190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes. Based on feedback and further deliberation, the ECDP writing committee down-graded recommendations regarding bile acid sequestrant use, recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe. For clarification, the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia, based on clinical criteria with and without genetic testing. Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians, unless there was a compelling reason or new evidence, in which case justification is provided.

Thermus and the Pink Discoloration Defect in Cheese.

A DNA sequencing-based strategy was applied to study the microbiology of Continental-type cheeses with a pink discoloration defect. The basis for this phenomenon has remained elusive, despite decades of research. The bacterial composition of cheese containing the defect was compared to that of control cheese using 16S rRNA gene and shotgun metagenomic sequencing as well as quantitative PCR (qPCR). Throughout, it was apparent that Thermus, a carotenoid-producing genus, was present at higher levels in defect-associated cheeses than in control cheeses. Prompted by this finding and data confirming the pink discoloration to be associated with the presence of a carotenoid, a culture-based approach was employed, and Thermus thermophilus was successfully cultured from defect-containing cheeses. The link between Thermus and the pinking phenomenon was then established through the cheese defect equivalent of Koch's postulates when the defect was recreated by the reintroduction of a T. thermophilus isolate to a test cheese during the manufacturing process. IMPORTANCE Pink discoloration in cheese is a defect affecting many cheeses throughout the world, leading to significant financial loss for the dairy industry. Despite decades of research, the cause of this defect has remained elusive. The advent of high-throughput, next-generation sequencing has revolutionized the field of food microbiology and, with respect to this study, provided a means of testing a possible microbial basis for this defect. In this study, a combined 16S rRNA, whole-genome sequencing, and quantitative PCR approach was taken. This resulted in the identification of Thermus, a carotenoid-producing thermophile, in defect-associated cheeses and the recreation of the problem in cheeses to which Thermus was added. This finding has the potential to lead to new strategies to eliminate this defect, and our method represents an approach that can be employed to investigate the role of microbes in other food defects of unknown origin.

Update on Cardiac Resynchronisation Therapy for Heart Failure.

Cardiac resynchronisation therapy (CRT) is well accepted therapy for the treatment of symptomatic systolic heart failure in defined patient subgroups. Large clinical trials over the past 20 years have shown that patients with a left ventricular (LV) systolic dysfunction and interventricular conduction delay benefit from this therapy. Recent advances in this field include the expansion indications for CRT to patients with mild heart failure and to those with a mildly depressed ejection fraction that require frequent right ventricular pacing. In addition, although CRT guidelines have included indications in atrial fibrillation, it is now clear that this is most effective when pacing is utilised nearly 100 % of the time, often requiring atrioventricular (AV) junction ablation. Strategies for optimising LV lead placement based on identifying late mechanical contraction or electrical delay are promising for maximising CRT response. Finally, the role of routine AV delay optimisation is no longer recommended based on the results of multicentre trials.