Efforts to reduce global cancer disparities begin with an understanding of geographic patterns in cancer incidence, mortality, and prevalence. Using the GLOBOCAN (2002) and Cancer Incidence in Five Continents databases, we describe overall cancer incidence, mortality, and prevalence, age-adjusted temporal trends, and age-specific incidence patterns in selected geographic regions of the world. For the eight most common malignancies-cancers of lung, breast, colon and rectum, stomach, prostate, liver, cervix, and esophagus-the most important risk factors, cancer prevention and control measures are briefly reviewed. In 2002, an estimated 11 million new cancer cases and 7 million cancer deaths were reported worldwide; nearly 25 million persons were living with cancer. Among the eight most common cancers, global disparities in cancer incidence, mortality, and prevalence are evident, likely due to complex interactions of nonmodifiable (ie, genetic susceptibility and aging) and modifiable risk factors (ie, tobacco, infectious agents, diet, and physical activity). Indeed, when risk factors among populations are intertwined with differences in individual behaviors, cultural beliefs and practices, socioeconomic conditions, and health care systems, global cancer disparities are inevitable. For the eight most common cancers, priorities for reducing cancer disparities are discussed.

Patterns of Cancer Incidence, Mortality, and Prevalence Across Five Continents: Defining Priorities to Reduce Cancer Disparities in Different Geographic Regions of the World

In contrast to adults, cardiac arrest in infants and children does not usually result from a primary cardiac cause. More often it is the terminal result of progressive respiratory failure or shock, also called an asphyxial arrest. Asphyxia begins with a variable period of systemic hypoxemia, hypercapnea, and acidosis, progresses to bradycardia and hypotension, and culminates with cardiac arrest.1

Another mechanism of cardiac arrest, ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), is the initial cardiac rhythm in approximately 5% to 15% of pediatric in-hospital and out-of-hospital cardiac arrests;2,–,9 it is reported in up to 27% of pediatric in-hospital arrests at some point during the resuscitation.6 The incidence of VF/pulseless VT cardiac arrest rises with age.2,4 Increasing evidence suggests that sudden unexpected death in young people can be associated with genetic abnormalities in myocyte ion channels resulting in abnormalities in ion flow (see “Sudden Unexplained Deaths,” below).

Since 2010 marks the 50th anniversary of the introduction of cardiopulmonary resuscitation (CPR),10 it seems appropriate to review the progressive improvement in outcome of pediatric resuscitation from cardiac arrest. Survival from in-hospital cardiac arrest in infants and children in the 1980s was around 9%.11,12 Approximately 20 years later, that figure had increased to 17%,13,14 and by 2006, to 27%.15,–,17 In contrast to those favorable results from in-hospital cardiac arrest, overall survival to discharge from out-of-hospital cardiac arrest in infants and children has not changed substantially in 20 years and remains at about 6% (3% for infants and 9% for children and adolescents).7,9

It is unclear why the improvement in outcome from in-hospital cardiac arrest has occurred, although earlier recognition and management of at-risk patients on general inpatient units …

https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.110.971101

Part 14: Pediatric Advanced Life Support 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

ContextCardiopulmonary resuscitation (CPR) guidelines recommend target values
for compressions, ventilations, and CPR-free intervals allowed for rhythm
analysis and defibrillation. There is little information on adherence to these
guidelines during advanced cardiac life support in the field.ObjectiveTo measure the quality of out-of-hospital CPR performed by ambulance
personnel, as measured by adherence to CPR guidelines.Design and SettingCase series of 176 adult patients with out-of-hospital cardiac arrest
treated by paramedics and nurse anesthetists in Stockholm, Sweden, London,
England, and Akershus, Norway, between March 2002 and October 2003. The defibrillators
recorded chest compressions via a sternal pad fitted with an accelerometer
and ventilations by changes in thoracic impedance between the defibrillator
pads, in addition to standard event and electrocardiographic recordings.Main Outcome MeasureAdherence to international guidelines for CPR.ResultsChest compressions were not given 48% (95% CI, 45%-51%) of the time
without spontaneous circulation; this percentage was 38% (95% CI, 36%-41%)
when subtracting the time necessary for electrocardiographic analysis and
defibrillation. Combining these data with a mean compression rate of 121/min
(95% CI, 118-124/min) when compressions were given resulted in a mean compression
rate of 64/min (95% CI, 61-67/min). Mean compression depth was 34 mm (95%
CI, 33-35 mm), 28% (95% CI, 24%-32%) of the compressions had a depth of 38
mm to 51 mm (guidelines recommendation), and the compression part of the duty
cycle was 42% (95% CI, 41%-42%). A mean of 11 (95% CI, 11-12) ventilations
were given per minute. Sixty-one patients (35%) had return of spontaneous
circulation, and 5 of 6 patients discharged alive from the hospital had normal
neurological outcomes.ConclusionsIn this study of CPR during out-of-hospital cardiac arrest, chest compressions
were not delivered half of the time, and most compressions were too shallow.
Electrocardiographic analysis and defibrillation accounted for only small
parts of intervals without chest compressions.

https://jamanetwork.com/journals/jama/articlepdf/200195/joc42116.pdf

Quality of cardiopulmonary resuscitation during out-of-hospital cardiac arrest

The Zygomycetes represent relatively uncommon isolates in the clinical laboratory, reflecting either environmental contaminants or, less commonly, a clinical disease called zygomycosis. There are two orders of Zygomycetes containing organisms that cause human disease, the Mucorales and the Entomophthorales. The majority of human illness is caused by the Mucorales. While disease is most commonly linked to Rhizopus spp., other organisms are also associated with human infection, including Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces, and Syncephalastrum spp. Although Mortierella spp. do cause disease in animals, there is no longer sufficient evidence to suggest that they are true human pathogens. The spores from these molds are transmitted by inhalation, via a variety of percutaneous routes, or by ingestion of spores. Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns. Zygomycosis occurs only rarely in immunocompetent hosts. The disease manifestations reflect the mode of transmission, with rhinocerebral and pulmonary diseases being the most common manifestations. Cutaneous, gastrointestinal, and allergic diseases are also seen. The Mucorales are associated with angioinvasive disease, often leading to thrombosis, infarction of involved tissues, and tissue destruction mediated by a number of fungal proteases, lipases, and mycotoxins. If the diagnosis is not made early, dissemination often occurs. Therapy, if it is to be effective, must be started early and requires combinations of antifungal drugs, surgical intervention, and reversal of the underlying risk factors. The Entomophthorales are closely related to the Mucorales on the basis of sexual growth by production of zygospores and by the production of coenocytic hyphae. Despite these similarities, the Entomophthorales and Mucorales have dramatically different gross morphologies, asexual reproductive characteristics, and disease manifestations. In comparison to the floccose aerial mycelium of the Mucorales, the Entomophthorales produce a compact, glabrous mycelium. The asexually produced spores of the Entomophthorales may be passively released or actively expelled into the environment. Human disease with these organisms occurs predominantly in tropical regions, with transmission occurring by implantation of spores via minor trauma such as insect bites or by inhalation of spores into the sinuses. Conidiobolus typically infects mucocutaneous sites to produce sinusitis disease, while Basidiobolus infections occur as subcutaneous mycosis of the trunk and extremities. The Entomophthorales are true pathogens, infecting primarily immunocompetent hosts. They generally do not invade blood vessels and rarely disseminate. Occasional cases of disseminated and angioinvasive disease have recently been described, primarily in immunocompromised patients, suggesting a possible emerging role for this organism as an opportunist.

Zygomycetes in Human Disease

Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients. These infections are becoming increasingly common, yet survival remains very poor. A greater understanding of the pathogenesis of the disease may lead to future therapies. For example, it is now clear that iron metabolism plays a central role in regulating mucormycosis infections and that deferoxamine predisposes patients to mucormycosis by inappropriately supplying the fungus with iron. These findings raise the possibility that iron chelator therapy may be useful to treat the infection as long as the chelator does not inappropriately supply the fungus with iron. Recent data support the concept that high-dose liposomal amphotericin is the preferred monotherapy for mucormycosis. However, several novel therapeutic strategies are available. These options include combination therapy using lipid-based amphotericin with an echinocandin or with an azole (largely itraconazole or posaconazole) or with all three. The underlying principles of therapy for this disease remain rapid diagnosis, reversal of underlying predisposition, and urgent surgical debridement.

Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

The Frank-Starling relationship generally has been examined with filling pressure as the index of preload, resulting in a curvilinear function that plateaus at higher filling pressures. To investigate this relationship further in the intact heart, 32 dogs were chronically instrumented with left ventricular and pleural micromanometers and with regional (10 dogs) or global (22 dogs) ultrasonic dimension transducers. Seven days after implantation, left ventricular pressure and regional or global dimensions were recorded in the conscious state. After autonomic blockade, preload was varied by vena caval occlusion. Myocardial function was assessed by calculating regional or global stroke work, and preload was measured as end-diastolic segment length or chamber volume. The relationship between stroke work and either end-diastolic segment length or chamber volume (termed the preload recruitable stroke work relationship) was highly linear in every study (mean r = .97) and could be quantified by a slope (MW) and x-intercept (LW). Previous nonlinear relationships between stroke work and filling pressure seemed to reflect the exponential diastolic pressure-volume curve. Over the physiologic range of systolic arterial pressures produced by infusion of nitroprusside or phenylephrine, no significant change was observed in MW or LW in the normal dog. Calcium infusion increased both regional and global MW by 71 +/- 19% and 65 +/- 9%, respectively (p less than .02), with no significant change in LW. To normalize for ventricular geometry and heart rate, stroke work was computed from circumferential stress-strain data and converted to myocardial power output, which was then plotted against end-diastolic circumferential strain. This relationship also was highly linear, and the slope, Mmp (mW/cm3 of myocardium), is proposed as a potential measure of intrinsic myocardial performance independent of loading, geometry, and heart rate.

Linearity of the Frank-Starling relationship in the intact heart: the concept of preload recruitable stroke work.

https://www.annalsthoracicsurgery.org/article/0003-4975(94)90243-7/pdf

Pulmonary mucormycosis: Results of medical and surgical therapy

In nine conscious, chronically instrumented dogs, ultrasonic dimension transducers measured left ventricular anterior-posterior and septal-free wall minor axis and major axis diameters. Matched micromanometers measured right and left ventricular transmural and transeptal pressures. Ventricular pressures and volumes were varied by inflation of implanted vena caval and pulmonary artery occluders, and the functional significance of the two types of ventricular interaction, i.e., direct and series, was determined. The left ventricle was represented by a modified ellipsoidal geometry. Left ventricular stroke volume calculated from the dimension data correlated well with that measured directly from ascending aortic electromagnetic flow probes during all interventions (r greater than or equal to 0.96). Partial pulmonary artery occlusion significantly increased right ventricular diastolic and systolic pressures as compared to values obtained during control and venal caval occlusion. During pulmonary artery occlusion, latitudinal septal eccentricity was increased throughout the cardiac cycle compared to control and vena caval occlusion (P less than 0.05), indicating leftward interventricular septal shifting and significant alteration of left ventricular shape. The normalized diastolic pressure-volume curve was shifted to the left with pulmonary artery occlusion compared to control and indicated a decrease in left ventricular chamber compliance. However, when selected cardiac cycles with similar end-diastolic volumes from vena caval and pulmonary artery occlusions were compared, parameters of left ventricular systolic function (stroke volume, percent systolic shortening, peak aortic blood flow, peak left ventricular pressure, and its first derivative) remained relatively constant. These data suggest that mean myocardial fiber length is the major preload determinant of left ventricular systolic function independent of chamber pressure and shape, and that direct ventricular interaction mediated by interventricular septal shifting has minimal effects on systolic myocardial performance in this model. Thus, series ventricular interaction during acute imbalances in biventricular loading, where the output of the right ventricle determines the input of the left, seems to be far more important than direct interaction to the regulation of overall cardiac function.

Dynamic ventricular interaction in the conscious dog.

The end-systolic pressure-volume relationship (ESPVR) has been shown to be an afterload-insensitive descriptor of ventricular inotropic state in the isolated heart. The purpose of this study was to examine the effects of changes in afterload, heart rate, intravascular volume, autonomic tone, and inotropic state on the ESPVR in conscious dogs. In 30 dogs, left ventricular and pleural pressures were measured with micromanometers, and left ventricular volume was assessed with global ultrasonic crystals. The ESPVR was obtained during vena caval occlusions in each dog during pharmacologic afterload interventions at control and after autonomic blockade. Analysis of variance techniques were used to compare the slopes (Emax) and intercepts (Vd) of ESPVR regression lines in a given study. All estimates of the ESPVR in conscious dogs involved large extrapolations to obtain estimates of Vd. Repeat determinations of Emax at control in the unblocked state were significantly different in six of eight dogs (p less than .05). After autonomic blockade, these differences were significant in only one of eight dogs. Changes in heart rate and volume loading had minimal effects on the ESPVR. In the absence of autonomic blockade, increases in inotropic state with either calcium or dobutamine tended to cause parallel shifts in the ESPVR. After autonomic blockade, Emax increased with augmentation of inotropic state, while Vd was unchanged. ESPVRs obtained at different afterloads showed statistically significant differences in Emax and in Vd in 12 of 14 dogs. However, no statistically significant relationship of Emax to afterload was observed. Thus, the ESPVR is probably valid in conscious dogs, but measurement with an intact cardiovascular system is hampered by statistically significant variability in Emax and Vd with changes in afterload. Baseline variability is magnified by the autonomic nervous system, probably mediated through sympathetic reflexes.

The end-systolic pressure-volume relationship in conscious dogs.

Quantification of myocardial performance after regional ischemic injury is difficult because available performance indexes are markedly dependent on concurrent load changes. To develop a more load-insensitive index of myocardial function during ischemia, eight conscious dogs were instrumented to measure left ventricular pressure with micromanometers and myocardial segment length with ultrasonic dimension transducers. Preload was varied by transient vena caval occlusion during control conditions, after 15 min of coronary occlusion, and at intervals during 24 h of reperfusion. Acute ischemia shifted the linear relationship between segmental stroke work (SW) and end-diastolic segment length (EDL) rightward, diminishing the slope and increasing the chi-intercept. Preload recruitable work area (PRWA), defined as the area under the SW-EDL curve, reflected changes in both slope and intercept. During acute ischemia, conventional performance indexes and PRWA decreased significantly and required up to 24 h of reperfusion to return to control values. Of all parameters examined, PRWA was most responsive to prolonged ischemic dysfunction after reperfusion and was insensitive to concurrent load changes. Thus PRWA provides improved precision in quantifying of myocardial dysfunction after regional ischemic injury. This parameter should be especially useful in assessing the subtle effects of acute interventions designed to modify functional recovery.

J. A. Spratt

Papers

Linearity of the Frank-Starling relationship in the intact heart: the concept of preload recruitable stroke work.

Pulmonary mucormycosis: Results of medical and surgical therapy

Dynamic ventricular interaction in the conscious dog.

The end-systolic pressure-volume relationship in conscious dogs.

Quantification of regional myocardial dysfunction after acute ischemic injury.