Tampa General Hospital

Jonathan Haidt’s The Righteous Mind seeks to explain why it is difficult for liberals and conservatives to get along. His aim is not just explanatory but also prescriptive. Once we understand that the differences between disputants spring from distinct moral views held by equally sincere people, then we will no longer have reason for deep political animus. Conservatives and Liberals have distinct (although somewhat overlapping) moral views and they understand human nature differently. He claims that these differences are best understood by consulting an array of psychological studies, key genetic findings, and the theoretical underpinnings of sociobiology. After summarizing his arguments, we isolate and discuss the three most important and contentious issues in his book. We argue that although the project’s motivation is noble and some of his findings are insightful, his key explanations, inferences, and prescriptions are wanting. We end by suggesting a way he could defend a weaker version of his view.

INTRODUCTION: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. METHODS: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. RESULTS: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. CONCLUSIONS: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01209169.

A consensus conference convened by the Society of Sarcopenia, Cachexia and Wasting Disorders has concluded that "Sarcopenia, ie, reduced muscle mass, with limited mobility" should be considered an important clinical entity and that most older persons should be screened for this condition. "Sarcopenia with limited mobility" is defined as a person with muscle loss whose walking speed is equal to or less than 1 m/s or who walks less than 400 m during a 6-minute walk, and who has a lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean of healthy persons between 20 and 30 years of age of the same ethnic group. The limitation in mobility should not clearly be a result of otherwise defined specific diseases of muscle, peripheral vascular disease with intermittent claudication, central and peripheral nervous system disorders, or cachexia. Clinically significant interventions are defined as an increase in the 6-minute walk of at least 50 meters or an increase of walking speed of at least 0.1 m/s.

BACKGROUND: Limb salvage for severe trauma has replaced amputation as the primary treatment in many trauma centers. However, long-term outcomes after limb reconstruction or amputation have not been fully evaluated. METHODS: We performed a multicenter, prospective, observational study to determine the functional outcomes of 569 patients with severe leg injuries resulting in reconstruction or amputation. The principal outcome measure was the Sickness Impact Profile, a multidimensional measure of self-reported health status (scores range from 0 to 100; scores for the general population average 2 to 3, and scores greater than 10 represent severe disability). Secondary outcomes included limb status and the presence or absence of major complications resulting in rehospitalization. RESULTS: At two years, there was no significant difference in scores for the Sickness Impact Profile between the amputation and reconstruction groups (12.6 vs. 11.8, P=0.53). After adjustment for the characteristics of the patients and their injuries, patients who underwent amputation had functional outcomes that were similar to those of patients who underwent reconstruction. Predictors of a poorer score for the Sickness Impact Profile included rehospitalization for a major complication, a low educational level, nonwhite race, poverty, lack of private health insurance, poor social-support network, low self-efficacy (the patient's confidence in being able to resume life activities), smoking, and involvement in disability-compensation litigation. Patients who underwent reconstruction were more likely to be rehospitalized than those who underwent amputation (47.6 percent vs. 33.9 percent, P=0.002). Similar proportions of patients who underwent amputation and patients who underwent reconstruction had returned to work by two years (53.0 percent and 49.4 percent, respectively). CONCLUSIONS: Patients with limbs at high risk for amputation can be advised that reconstruction typically results in two-year outcomes equivalent to those of amputation.

From January 1987 to September 1990, 132 displaced intraarticular calcaneal fractures were treated operatively using a lateral approach, lag screws, and side plate without bone graft. To evaluate the results, a classification for intraarticular calcaneal fractures was developed, based on standardized coronal and transverse computed tomography (CT) scans of both feet. Type 1 fractures were nondisplaced (and received nonoperative treatment); Type II were two-part or split fractures; Type III were three-part or split depression fractures; and Type IV were four-part or highly comminuted articular fractures. Results were evaluated using the Maryland Foot Score and repeat CT scans. One hundred twenty cases were available for a minimum of one year follow-up evaluation (range, 12-56 months; mean, 29.3 months). Roentgenographic evaluation of calcaneal body dimensions showed restoration of heel height (98%), width (110%), and length (100%) to virtually normal in all cases, regardless of preoperative displacement. Roentgenographically, articular reduction was anatomic in 68 of 79 (86%) Type II fractures, 18 of 30 (60%) Type III fractures, and 0 of 11 (0%) Type IV fractures. Excellent or good clinical results occurred in 58 of 79 (73%) Type II fractures, 21 of 30 (70%) Type III fractures, and one of 11 (9%) Type IV fractures. When excellent and good clinical results were compared by year, a distinct learning curve appeared (1987, 27%; 1988, 54%; 1989, 74%; 1990, 84%). Despite an improved outcome for Type II and III fractures with increasing surgical experience, the results of operative intervention in Type IV fractures were no better, even after four years.(ABSTRACT TRUNCATED AT 250 WORDS)

Preclinical studies suggest ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinson's disease (PD), and a pilot clinical study using (18)F-dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with ropinirole compared with levodopa. This prospective, 2-year, randomized, double-blind, multinational study compared the rates of loss of dopamine-terminal function in de novo patients with clinical and (18)F-dopa PET evidence of early PD, randomized 1 to 1 to receive either ropinirole or levodopa. The primary outcome measure was reduction in putamen (18)F-dopa uptake (Ki) between baseline and 2-year PET. Of 186, 162 randomized patients were eligible for analysis. A blinded, central, region-of-interest analysis showed a significantly lower reduction (p = 0.022) in putamen Ki over 2 years with ropinirole (-13.4%; n = 68) compared with levodopa (-20.3%; n = 59; 95% confidence interval [CI], 0.65-13.06). Statistical parametric mapping localized lesser reductions in (18)F-dopa uptake in the putamen and substantia nigra with ropinirole. The greatest Ki decrease in each group was in the putamen (ropinirole, -14.1%; levodopa, -22.9%; 95% CI, 4.24-13.3), but the decrease was significantly lower with ropinirole compared with levodopa (p < 0.001). Ropinirole is associated with slower progression of PD than levodopa as assessed by (18)F-dopa PET.

MESS (Mangled Extremity Severity Score) is a simple rating scale for lower extremity trauma, based on skeletal/soft-tissue damage, limb ischemia, shock, and age. Retrospective analysis of severe lower extremity injuries in 25 trauma victims demonstrated a significant difference between MESS values for 17 limbs ultimately salvaged (mean, 4.88 +/- 0.27) and nine requiring amputation (mean, 9.11 +/- 0.51) (p less than 0.01). A prospective trial of MESS in lower extremity injuries managed at two trauma centers again demonstrated a significant difference between MESS values of 14 salvaged (mean, 4.00 +/- 0.28) and 12 doomed (mean, 8.83 +/- 0.53) limbs (p less than 0.01). In both the retrospective survey and the prospective trial, a MESS value greater than or equal to 7 predicted amputation with 100% accuracy. MESS may be useful in selecting trauma victims whose irretrievably injured lower extremities warrant primary amputation.

OBJECTIVE: The timing of tracheotomy in patients requiring mechanical ventilation is unknown. The effects of early percutaneous dilational tracheotomy compared with delayed tracheotomy in critically ill medical patients needing prolonged mechanical ventilation were assessed. DESIGN: Prospective, randomized study. SETTING: Medical intensive care units. PATIENTS: One hundred and twenty patients projected to need ventilation >14 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were prospectively randomized to either early percutaneous tracheotomy within 48 hrs or delayed tracheotomy at days 14-16. Time in the intensive care unit and on mechanical ventilation and the cumulative frequency of pneumonia, mortality, and accidental extubation were documented. The airway was assessed for oral, labial, laryngeal, and tracheal damage. Early group showed significantly less mortality (31.7% vs. 61.7%), pneumonia (5% vs. 25%), and accidental extubations compared with the prolonged translaryngeal group (0 vs. 6). The early tracheotomy group spent less time in the intensive care unit (4.8 +/- 1.4 vs. 16.2 +/- 3.8 days) and on mechanical ventilation (7.6 +/- 2.0 vs. 17.4 +/- 5.3 days). There was also significantly more damage to mouth and larynx in the prolonged translaryngeal intubation group. CONCLUSIONS: This study demonstrates that the benefits of early tracheotomy outweigh the risks of prolonged translaryngeal intubation. It gives credence to the practice of subjecting this group of critically ill medical patients to early tracheotomy rather than delayed tracheotomy.

BACKGROUND: Alendronate, an aminobisphosphonate and a selective inhibitor of osteoclast-mediated bone resorption, is used to treat osteoporosis in postmenopausal women and Paget's disease of bone. Aminobiphosphonates can irritate the upper gastrointestinal mucosa. METHODS: We describe three patients who had severe esophagitis shortly after starting to take alendronate and also analyze adverse esophageal effects reported to Merck, the manufacturer, through postmarketing surveillance. RESULTS: As of March 5, 1996, alendronate had been prescribed for an estimated 475,000 patients worldwide, and 1213 reports of adverse effects had been received. A total of 199 patients had adverse effects related to the esophagus; in 51 of these patients (26 percent), including the 3 we describe in case reports, adverse effects were categorized as serious or severe. Thirty-two patients (16 percent) were hospitalized, and two were temporarily disabled. Endoscopic findings generally indicated chemical esophagitis, with erosions or ulcerations and exudative inflammation accompanied by thickening of the esophageal wall. Bleeding was rare, and stomach or duodenal involvement unusual. In patients for whom adequate information was available, esophagitis seemed to be associated with swallowing alendronate with little or no water, lying down during or after ingestion of the tablet, lying down during or after ingestion of the tablet, continuing to take alendronate after the onset of symptoms, and having preexisting esophageal disorders. CONCLUSIONS: Alendronate can cause chemical esophagitis, including severe ulcerations, in some patients. Recommendations to reduce the risk of esophagitis include swallowing alendronate with 180 to 240 ml (6 to 8 oz) of water on arising in the morning, remaining upright for at least 30 minutes after swallowing the tablet and until the first food of the day has been ingested, and discontinuing the drug promptly if esophageal symptoms develop.

OBJECTIVES: The aim of this study was to evaluate the safety and effectiveness of percutaneous mechanical thrombectomy using the FlowTriever System (Inari Medical, Irvine, California) in a prospective trial of patients with acute intermediate-risk pulmonary embolism (PE). BACKGROUND: Catheter-directed thrombolysis has been shown to improve right ventricular (RV) function in patients with PE. However, catheter-directed thrombolysis increases bleeding risk and many patients with PE have relative and absolute contraindications to thrombolysis. METHODS: Patients with symptomatic, computed tomography-documented PE and RV/left ventricular (LV) ratios ≥0.9 were eligible for enrollment. The primary effectiveness endpoint was core laboratory-assessed change in RV/LV ratio. The primary safety endpoint comprised device-related death, major bleeding, treatment-related clinical deterioration, pulmonary vascular injury, or cardiac injury within 48 h of thrombectomy. RESULTS: From April 2016 to October 2017, 106 patients were treated with the FlowTriever System at 18 U.S. sites. Two patients (1.9%) received adjunctive thrombolytics and were analyzed separately. Mean procedural time was 94 min; mean intensive care unit stay was 1.5 days. Forty-three patients (41.3%) did not require any intensive care unit stay. At 48 h post-procedure, average RV/LV ratio reduction was 0.38 (25.1%; p < 0.0001). Four patients (3.8%) experienced 6 major adverse events, with 1 patient (1.0%) experiencing major bleeding. One patient (1.0%) died, of undiagnosed breast cancer, through 30-day follow-up. CONCLUSIONS: Percutaneous mechanical thrombectomy with the FlowTriever System appears safe and effective in patients with acute intermediate-risk PE, with significant improvement in RV/LV ratio and minimal major bleeding. Potential advantages include immediate thrombus removal, absence of thrombolytic complications, and reduced need for post-procedural critical care.

OBJECTIVES: Considerable morbidity persists among survivors of breast cancer (BC) including high levels of psychological stress, anxiety, depression, fear of recurrence, and physical symptoms including pain, fatigue, and sleep disturbances, and impaired quality of life. Effective interventions are needed during this difficult transitional period. METHODS: We conducted a randomized controlled trial of 84 female BC survivors (Stages 0-III) recruited from the H. Lee Moffitt Cancer and Research Institute. All subjects were within 18 months of treatment completion with surgery and adjuvant radiation and/or chemotherapy. Subjects were randomly assigned to a 6-week Mindfulness-Based Stress Reduction (MBSR) program designed to self-regulate arousal to stressful circumstances or symptoms (n=41) or to usual care (n=43). Outcome measures compared at 6 weeks by random assignment included validated measures of psychological status (depression, anxiety, perceived stress, fear of recurrence, optimism, social support) and psychological and physical subscales of quality of life (SF-36). RESULTS: Compared with usual care, subjects assigned to MBSR(BC) had significantly lower (two-sided p<0.05) adjusted mean levels of depression (6.3 vs 9.6), anxiety (28.3 vs 33.0), and fear of recurrence (9.3 vs 11.6) at 6 weeks, along with higher energy (53.5 vs 49.2), physical functioning (50.1 vs 47.0), and physical role functioning (49.1 vs 42.8). In stratified analyses, subjects more compliant with MBSR tended to experience greater improvements in measures of energy and physical functioning. CONCLUSIONS: Among BC survivors within 18 months of treatment completion, a 6-week MBSR(BC) program resulted in significant improvements in psychological status and quality of life compared with usual care.

From January 1987 to September 1990, 132 displaced intraarticular calcaneal fractures were treated operatively using a lateral approach, lag screws, and side plate without bone graft. To evaluate the results, a classification for intraarticular calcaneal fractures was developed, based on standardized coronal and transverse computed tomography (CT) scans of both feet. Type I fractures were nondisplaced (and received nonoperative treatment); Type II were two-part or split fractures; Type III were three-part or split depression fractures; and Type IV were four-part or highly comminuted articular fractures. Results were evaluated using the Maryland Foot Score and repeat CT scans. One hundred twenty cases were available for a minimum of one year follow-up evaluation (range, 12–56 months; mean, 29.3 months). Roentgenographic evaluation of calcaneal body dimensions showed restoration of heel height (98%), width (110%), and length (100%) to virtually normal in all cases, regardless of preoperative displacement. Roentgenographically, articular reduction was anatomic in 68 of 79 (86%) Type II fractures, 18 of 30 (60%) Type III fractures, and 0 of 11 (0%) Type IV fractures. Excellent or good clinical results occurred in 58 of 79 (73%) Type II fractures, 21 of 30 (70%) Type III fractures, and one of 11 (9%) Type IV fractures. When excellent and good clinical results were compared by year, a distinct learning curve appeared (1987, 27%; 1988, 54%; 1989, 74%; 1990, 84%). Despite an improved outcome for Type II and III fractures with increasing surgical experience, the results of operative intervention in Type IV fractures were no better, even after four years. This classification aids the surgeon in perioperative decision making, because it has prognostic significance. Results deteriorate as the number of articular fragments increase. This appears to be directly related to the difficulty obtaining an anatomic reduction of the joint. Furthermore, although an anatomic articular reduction is necessary for a good result, it does not guarantee it. Additionally, a learning curve exists for surgeons engaged in operative surgery of Type II and III fractures. Patients with Type IV fractures can expect inferior operative results irrespective of the surgeon's experience, and consideration should be given to primary arthrodesis.

RATIONALE: We recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest. OBJECTIVES: We now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients. METHODS: We conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test. MEASUREMENTS AND MAIN RESULTS: Urinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]). CONCLUSIONS: Urinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962).

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to treat cardiogenic shock. However, VA-ECMO might hamper myocardial recovery. The Impella unloads the left ventricle. This study aimed to evaluate whether left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO was associated with lower mortality. Methods: Data from 686 consecutive patients with cardiogenic shock treated with VA-ECMO with or without left ventricular unloading using an Impella at 16 tertiary care centers in 4 countries were collected. The association between left ventricular unloading and 30-day mortality was assessed by Cox regression models in a 1:1 propensity score–matched cohort. Results: Left ventricular unloading was used in 337 of the 686 patients (49%). After matching, 255 patients with left ventricular unloading were compared with 255 patients without left ventricular unloading. In the matched cohort, left ventricular unloading was associated with lower 30-day mortality (hazard ratio, 0.79 [95% CI, 0.63–0.98]; P =0.03) without differences in various subgroups. Complications occurred more frequently in patients with left ventricular unloading: severe bleeding in 98 (38.4%) versus 45 (17.9%), access site–related ischemia in 55 (21.6%) versus 31 (12.3%), abdominal compartment in 23 (9.4%) versus 9 (3.7%), and renal replacement therapy in 148 (58.5%) versus 99 (39.1%). Conclusions: In this international, multicenter cohort study, left ventricular unloading was associated with lower mortality in patients with cardiogenic shock treated with VA-ECMO, despite higher complication rates. These findings support use of left ventricular unloading in patients with cardiogenic shock treated with VA-ECMO and call for further validation, ideally in a randomized, controlled trial.

OBJECTIVE: To examine the correlation between syndesmotic malreduction and functional outcome. DESIGN: Prospective evaluation of bilateral computed tomography scans and functional outcome scores. SETTING: Level I regional trauma center. MATERIALS AND METHODS: From January 1, 2004, to December 31, 2006, 107 of 681 operatively treated ankle fractures (15.7%) had associated syndesmotic injuries requiring reduction and fixation. All patients available at a minimum of 2 years postindex procedure underwent clinical and radiographic examination, computed tomographic (CT) scanning of both ankles (injured and uninjured), and functional outcome scoring using the Short Form Musculoskeletal Assessment and Olerud/Molander questionnaires. RESULTS: Sixty-eight of 107 (63.5%) syndesmotic injuries in 68 patients were available for follow-up. Twenty-seven (39%) were malreduced (rotational or translational asymmetry) when compared with the contralateral uninjured syndesmotic joint. Fifteen percent of the open syndesmotic reductions were malreduced on postoperative CT scans, whereas 44% (A/B) of the closed syndesmotic reductions were malreduced on postoperative CT scan (P = 0.11). Patients with a malreduced syndesmosis recorded significantly worse functional outcome scores (P < 0.05) on both the Short Form Musculoskeletal Assessment and Olerud/Molander questionnaires when compared with those patients whose syndesmosis had healed in anatomic alignment. CONCLUSIONS: At a minimum of 2 years follow-up, patients with malreduced syndesmotic injuries demonstrated significantly worse functional outcome using the Short Form Musculoskeletal Assessment and Olerud/Molander questionnaires. Open reduction of the syndesmosis resulted in a substantially lower rate of malreduction when evaluated by postoperative CT scan. Based on these findings, we recommend that surgeons not only perform a direct, open visualization of the syndesmosis during the reduction maneuver, but obtain a postoperative CT scan with comparison to the contralateral extremity as well. If the syndesmosis is found to be malreduced, consideration must be given to revising the osteosynthesis. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

PURPOSE: The prognosis for unresectable pancreatic cancer remains dismal (1-year survival rate, < 10%; 5-year survival rate, < 5%). Recent advances in conventional chemotherapy and novel molecular treatment strategies warrant investigation. This, the largest randomized study in pancreatic cancer performed to date, compares marimastat, the first of a new class of agents, with gemcitabine. PATIENTS AND METHODS: Four hundred fourteen patients with unresectable pancreatic cancer were randomized to receive marimastat 5, 10, or 25 mg bid or gemcitabine 1,000 mg/m2. The primary end point was survival. Progression-free survival, patient benefit, and safety were also assessed. RESULTS: There was no significant difference in survival between 5, 10, or 25 mg of marimastat and gemcitabine (P =.19). Median survival times were 111, 105, 125, and 167 days, respectively, and 1-year survival rates were 14%, 14%, 20%, and 19%, respectively. There was a significant difference in survival rates between patients treated with gemcitabine and marimastat 5 and 10 mg (P <.003). Both agents were well tolerated, although grade 3 or 4 toxicities were reported in 22% and 12% of the gemcitabine- and marimastat-treated patients, respectively. The major toxicity of marimastat was musculoskeletal (44% of marimastat patients, compared with 12% of gemcitabine patients; musculoskeletal toxicity was severe in only 8% of marimastat patients). CONCLUSION: The results of this study provide evidence of a dose response for marimastat in patients with advanced pancreatic cancer. The 1-year survival rate for patients receiving marimastat 25 mg was similar to that of patients receiving gemcitabine. In view of the manageable tolerability of marimastat and its ease of administration, further studies are warranted.

IMPORTANCE: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. OBJECTIVE: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. RESULTS: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant. CONCLUSIONS AND RELEVANCE: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02522871.

BACKGROUND: Transmyocardial revascularization involves the creation of channels in the myocardium with a laser to relieve angina. We compared the safety and efficacy of transmyocardial revascularization performed with a holmium laser with those of medical therapy in patients with refractory class IV angina (according to the criteria of the Canadian Cardiovascular Society). METHODS: In a prospective study conducted between March 1996 and July 1998 at 18 centers, 275 patients with medically refractory class IV angina and coronary disease that could not be treated with percutaneous or surgical revascularization were randomly assigned to receive transmyocardial revascularization followed by continued medical therapy (132 patients) or medical therapy alone (143 patients). RESULTS: After one year of follow-up, 76 percent of the patients who had undergone transmyocardial revascularization had improvement in angina (a reduction of two or more classes), as compared with 32 percent of the patients who received medical therapy alone (P<0.001). Kaplan-Meier survival estimates at one year (based on an intention-to-treat analysis) were similar for the patients assigned to undergo transmyocardial revascularization and those assigned to receive medical therapy alone (84 percent and 89 percent, respectively; P=0.23). At one year, the patients in the transmyocardial-revascularization group had a significantly higher rate of survival free of cardiac events (54 percent, vs. 31 percent in the medical-therapy group; P<0.001), a significantly higher rate of freedom from treatment failure (73 percent vs. 47 percent, P<0.001), and a significantly higher rate of freedom from cardiac-related rehospitalization (61 percent vs. 33 percent, P<0.001). Exercise tolerance and quality-of-life scores were also significantly higher in the transmyocardial-revascularization group than in the medical-therapy group (exercise tolerance, 5.0 MET [metabolic equivalent] vs. 3.9 MET; P=0.05); quality-of-life score, 21 vs. 12; P=0.003). However, there were no differences in myocardial perfusion between the two groups, as assessed by thallium scanning. CONCLUSIONS: Patients with refractory angina who underwent transmyocardial revascularization and received continued medical therapy, as compared with similar patients who received medical therapy alone, had a significantly better outcome with respect to improvement in angina, survival free of cardiac events, freedom from treatment failure, and freedom from cardiac-related rehospitalization.

Abstract Obesity has emerged as one of the most serious public health concerns in the 21st century. Obese children tend to become obese adults. The dramatic rise in pediatric obesity closely parallels the rapid increase in the prevalence of adult obesity. As overweight children become adults they face the multitude of health problems associated with obesity at younger ages. The morbidity and mortality associated with obesity continue to increase. Obesity is one of the leading causes of preventable death. Complications of obesity include cardiovascular risks, hypertension, dyslipidemia, endothelial dysfunction, type 2 diabetes mellitus and impaired glucose tolerance, acanthosis nigricans, hepatic steatosis, premature puberty, hypogonadism and polycystic ovary syndrome, obstructive sleep disorder, orthopedic complications, cholelithiasis and pseudotumor cerebri. Genetic and molecular and environmental factors play an important role in the assessment and management of obesity. © 2007 Wiley‐Liss, Inc.

The proportion of patients with psychogenic nonepileptic seizures (PNES) who also have epilepsy has been reported to vary from 10% to over 50%. The authors reviewed all 32 patients diagnosed with PNES in our EEG-video monitoring unit over a period of 1 year, and only 3 (9.4%) had interictal epileptiform discharges to support a coexisting diagnosis of epilepsy. Thus, the authors believe that only a small proportion of patients with PNES have coexisting epilepsy.