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"Sutton, Robert"
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Scaling up excellence : getting to more without settling for less
\"In Scaling Up Excellence, bestselling author Bob Sutton and Stanford colleague Huggy Rao tackle the topic that obsesses businesses large and small, from start-ups to Fortune 500 companies--how to scale up their businesses and spread excellence throughout the organizational culture\"-- Provided by publisher.
Book
Acute Pancreatitis: Diagnosis and Treatment
Acute pancreatitis is a common indication for hospital admission, increasing in incidence, including in children, pregnancy and the elderly. Moderately severe acute pancreatitis with fluid and/or necrotic collections causes substantial morbidity, and severe disease with persistent organ failure causes significant mortality. The diagnosis requires two of upper abdominal pain, amylase/lipase ≥ 3 ×upper limit of normal, and/or cross-sectional imaging findings. Gallstones and ethanol predominate while hypertriglyceridaemia and drugs are notable among many causes. Serum triglycerides, full blood count, renal and liver function tests, glucose, calcium, transabdominal ultrasound, and chest imaging are indicated, with abdominal cross-sectional imaging if there is diagnostic uncertainty. Subsequent imaging is undertaken to detect complications, for example, if C-reactive protein exceeds 150 mg/L, or rarer aetiologies. Pancreatic intracellular calcium overload, mitochondrial impairment, and inflammatory responses are critical in pathogenesis, targeted in current treatment trials, which are crucially important as there is no internationally licenced drug to treat acute pancreatitis and prevent complications. Initial priorities are intravenous fluid resuscitation, analgesia, and enteral nutrition, and when necessary, critical care and organ support, parenteral nutrition, antibiotics, pancreatic exocrine and endocrine replacement therapy; all may have adverse effects. Patients with local complications should be referred to specialist tertiary centres to guide further management, which may include drainage and/or necrosectomy. The impact of acute pancreatitis can be devastating, so prevention or reduction of the risk of recurrence and progression to chronic pancreatitis with an increased risk of pancreas cancer requires proactive management that should be long term for some patients.
Journal Article
The friction project : how smart leaders make the right things easier and the wrong things harder
\"Every organization is plagued by destructive friction-the forces that make it harder, more complicated, or downright impossible to get anything done. Yet some forms of friction are incredibly useful, and leaders who attempt to improve workplace efficiency often make things even worse. Drawing from seven years of hands-on research, The Friction Project by bestselling authors Robert I. Sutton and Huggy Rao teaches readers how to become \"friction fixers,\" so that teams and organizations don't squander the zeal, damage the health, and throttle the creativity and productivity of good people--or burn through cash and other precious resources. Sutton and Rao kick off the book by unpacking how skilled friction fixers think and act like trustees of others' time. They provide friction forensics to help readers identify where to avert and repair bad organizational friction and where to maintain and inject good friction. Then their help pyramid shows how friction fixers do their work, which ranges from reframing friction troubles they can't fix right now so they feel less threatening to designing and repairing organizations. The heart of the book digs into the causes and solutions for five of the most common and damaging friction troubles: oblivious leaders, addition sickness, broken connections, jargon monoxide, and fast and frenzied people and teams. Sound familiar? Sutton and Rao are here to help. They wrap things up with lessons for leading your own friction project, including linking little things to big things; the power of civility, caring, and love for propelling designs and repairs; and embracing the mess that is an inevitable part of the process (while still trying to clean it up)\"-- Provided by publisher.
Book
Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders
Histones are positively charged nuclear proteins that facilitate packaging of DNA into nucleosomes common to all eukaryotic cells. Upon cell injury or cell signalling processes, histones are released passively through cell necrosis or actively from immune cells as part of extracellular traps. Extracellular histones function as microbicidal proteins and are pro‐thrombotic, limiting spread of infection or isolating areas of injury to allow for immune cell infiltration, clearance of infection and initiation of tissue regeneration and repair. Histone toxicity, however, is not specific to microbes and contributes to tissue and end‐organ injury, which in cases of systemic inflammation may lead to organ failure and death. This review details the processes of histones release in acute inflammation, the mechanisms of histone‐related tissue toxicity and current and future strategies for therapy targeting histones in acute inflammatory diseases.
Journal Article
دليل النجاة من الحمقى : كيف تتعامل مع الأشخاص الذين يسيئون معاملتك
لقد طورت هذه الإستراتيجيات والنصائح على مدار سنوات عديدة، وبصرف النظر عما كان من المفترض أن أعمل عليه خلال العقد الماضي، كنت أقضي ساعة أو اثنتين معظم الأيام في التفكير، والقراءة، والحديث، والكتابة عن الحمقى، والبحث عن الترياق المضاد لهم، ومراقبة سلوك الأشخاص الوقحين، أو المعتدين- من حين لآخر - وهم يمارسون حياتهم الطبيعية. وكانت النتيجة هي أنني أصدرت هذا الكتاب، الذي يقدم أفضل النصائح التي توصلت إليها بشأن كيفية التعامل مع من يضطهدون غيرهم، أو يحطون من قدرهم، أو لا يحترمونهم، أو يثبطون عزيمتهم، وبخاصة في مكان العمل. ولعل الدروس الواردة في هذا الكتاب وثيقة الصلة بمشكلة اضطرار المتطوعين في المؤسسات غير الربحية، والمدارس، ومختلف دور العبادة إلى العمل مع الحمقى، وكذلك بالسلوكيات الوقحة التي يمارسونها في الأماكن العامة، مثل مترو الأنفاق، والمطارات، والمراكز التجارية، والملاعب الرياضية. وقد صيغت الإستراتيجيات والنصائح الواردة في هذا الكتاب بناء على أبحاث علمية، أجريت على الأشخاص الذين لا يحترمون غيرهم، ويحطون من قدر الآخرين ؛ وقد ازداد عددهم زيادة جنونية في السنوات الأخيرة.
Book
Critical thresholds: key to unlocking the door to the prevention and specific treatments for acute pancreatitis
Acute pancreatitis (AP), an acute inflammatory disorder of the exocrine pancreas, is one of the most common gastrointestinal diseases encountered in emergency departments with no specific treatments. Laboratory-based research has formed the cornerstone of endeavours to decipher the pathophysiology of AP, because of the limitations of such study in human beings. While this has provided us with substantial understanding, we cannot answer several pressing questions. These are: (a) Why is it that only a minority of individuals with gallstones, or who drink alcohol excessively, or are exposed to other causative factors develop AP? (b) Why do only some develop more severe manifestations of AP with necrosis and/or organ failure? (c) Why have we been unable to find an effective therapeutic for AP? This manuscript provides a state-of-the-art review of our current understanding of the pathophysiology of AP providing insights into the unanswered clinical questions. We describe multiple protective factors operating in most people, and multiple stressors that in a minority induce AP, independently or together, via amplification loops. We present testable hypotheses aimed at halting progression of severity for the development of effective treatments for this common unpredictable disease.
Journal Article
Epinephrine’s effects on cerebrovascular and systemic hemodynamics during cardiopulmonary resuscitation
Background
Despite controversies, epinephrine remains a mainstay of cardiopulmonary resuscitation (CPR). Recent animal studies have suggested that epinephrine may decrease cerebral blood flow (CBF) and cerebral oxygenation, possibly potentiating neurological injury during CPR. We investigated the cerebrovascular effects of intravenous epinephrine in a swine model of pediatric in-hospital cardiac arrest. The primary objectives of this study were to determine if (1) epinephrine doses have a significant acute effect on CBF and cerebral tissue oxygenation during CPR and (2) if the effect of each subsequent dose of epinephrine differs significantly from that of the first.
Methods
One-month-old piglets (
n
= 20) underwent asphyxia for 7 min, ventricular fibrillation, and CPR for 10–20 min. Epinephrine (20 mcg/kg) was administered at 2, 6, 10, 14, and 18 min of CPR. Invasive (laser Doppler, brain tissue oxygen tension [PbtO
2
]) and noninvasive (diffuse correlation spectroscopy and diffuse optical spectroscopy) measurements of CBF and cerebral tissue oxygenation were simultaneously recorded. Effects of subsequent epinephrine doses were compared to the first.
Results
With the first epinephrine dose during CPR, CBF and cerebral tissue oxygenation increased by > 10%, as measured by each of the invasive and noninvasive measures (
p
< 0.001). The effects of epinephrine on CBF and cerebral tissue oxygenation decreased with subsequent doses. By the fifth dose of epinephrine, there were no demonstrable increases in CBF of cerebral tissue oxygenation. Invasive and noninvasive CBF measurements were highly correlated during asphyxia (slope effect 1.3,
p
< 0.001) and CPR (slope effect 0.20,
p
< 0.001).
Conclusions
This model suggests that epinephrine increases CBF and cerebral tissue oxygenation, but that effects wane following the third dose. Noninvasive measurements of neurological health parameters hold promise for developing and directing resuscitation strategies.
Journal Article
Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma
The objective of this study was to investigate whether the preoperative platelet-lymphocyte (P/L) ratio represents a significant prognostic index in resected pancreatic ductal adenocarcinoma.
A total of 110 patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma over a 10-year period were identified from a prospectively maintained database.
The preoperative P/L ratio was found to be a more significant prognostic marker (
P < .001) than either the lymphocyte count (
P = .007) or platelet count (
P = .068) on univariate Cox survival analysis. The median overall survival in patients with a P/L ratio of 150 or less (n = 48) was 19.7 months, 13.7 months in those with a P/L ratio of 151 to 300 (n = 43), and 5.8 months in patients with a value of greater than 300 (n = 19) (log-rank,
P = .006). The preoperative P/L ratio retained significance on multivariate analysis (
P < .001), along with tumor size (
P = .010) and lymph node ratio (
P = .013).
The preoperative P/L ratio represents a significant independent prognostic index in patients of resected pancreatic adenocarcinoma.
Journal Article
Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis
ObjectiveThe benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP.DesignMajor databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined.ResultsA total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, p<0.00001; I2=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I2=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking.ConclusionsPERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition.
Journal Article
Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP
ObjectiveAcute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established.DesignWe investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis.ResultsMPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished.ConclusionsThis work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease.
Journal Article