Regorafenib-associated hand-foot skin reaction: practical advice on diagnosis, prevention, and management.

BACKGROUND: Regorafenib is an orally available, small-molecule multikinase inhibitor with international marketing authorizations for use in colorectal cancer and gastrointestinal stromal tumors. In clinical trials, regorafenib showed a consistent and predictable adverse-event profile, with hand-foot skin reaction (HFSR) among the most clinically significant toxicities. This review summarizes the clinical characteristics of regorafenib-related HFSR and provides practical advice on HFSR management to enable health care professionals to recognize, pre-empt, and effectively manage the symptoms, thereby allowing patients to remain on active therapy for as long as possible. DESIGN: This review is based on a systematic literature search of the PubMed database (using synonyms of HFSR, regorafenib, and skin toxicities associated with targeted therapies or cytotoxic chemotherapy). However, as this search identified very few articles, the authors also use their clinical experience as oncologists and dermatologists managing patients with treatment-related HFSR to provide recommendations on recognition and management of HFSR in regorafenib-treated patients. RESULTS: Regorafenib-related HFSR is similar to that seen with other multikinase inhibitors (e.g. sorafenib, sunitinib, cabozantinib, axitinib, and pazopanib) but differs from the hand-foot syndrome seen with cytotoxic chemotherapies (e.g. fluoropyrimidines, anthracyclines, and taxanes). There have been no controlled trials of symptomatic management of regorafenib-related HFSR, and limited good-quality evidence from randomized clinical trials of effective interventions for HFSR associated with other targeted therapies. Recommendations on prevention and management of regorafenib-related HFSR in this review are therefore based on the expert opinion of the authors (dermatologists and oncologists with expertise in the management of treatment-related skin toxicities and oncologists involved in clinical trials of regorafenib) and tried-and-tested empirical experience with other multikinase inhibitors and cytotoxic chemotherapies. CONCLUSIONS: As recommended in this review, treatment modifications and supportive measures to prevent, reduce, and manage HFSR can allow patients to continue regorafenib at the optimal dose to derive benefit from treatment.

Skin cancer risk in BRCA1/2 mutation carriers.

Women with BRCA1/2 mutations have an elevated risk of breast and ovarian cancer. These patients and their clinicians are often concerned about their risk for other cancers, including skin cancer. Research evaluating the association between BRCA1/2 mutations and skin cancer is limited and has produced inconsistent results. Herein, we review the current literature on the risk of melanoma and nonmelanoma skin cancers in BRCA1/2 mutation carriers. No studies have shown a statistically significant risk of melanoma in BRCA1 families. BRCA2 mutations have been linked to melanoma in large breast and ovarian cancer families, though a statistically significant elevated risk was reported in only one study. Five additional studies have shown some association between BRCA2 mutations and melanoma, while four studies did not find any association. With respect to nonmelanoma skin cancers, studies have produced conflicting results. Given the current state of medical knowledge, there is insufficient evidence to warrant increased skin cancer surveillance of patients with a confirmed BRCA1/2 mutation or a family history of a BRCA1/2 mutation, in the absence of standard risk factors. Nonetheless, suspected BRCA1/2 mutation carriers should be counselled about skin cancer risks and may benefit from yearly full skin examinations.

Cardiac tamponade following minimally invasive direct coronary artery bypass.

We report a case of cardiac tamponade resulting in a death following minimally invasive direct coronary artery bypass. Despite absence of clinical symptoms at the time of hospital discharge, cardiac tamponade physiology may have been evident on close evaluation of Doppler studies of the left internal mammary artery. Performance of a predischarge transthoracic echocardiogram may have been confirmatory and lifesaving.

Physical activity outcomes of CHAMPS II: a physical activity promotion program for older adults.

BACKGROUND: Despite well-known benefits of physical activity for older adults, about two thirds are underactive. Community-based programs are needed to facilitate increased physical activity. We examine the effectiveness of CHAMPS II, an inclusive, choice-based physical activity promotion program to increase lifetime physical activity levels of seniors. CHAMPS guided participants to choose activities that took into account their health, preferences, and abilities. It offered information on ways for them to exercise safely, motivate themselves, overcome barriers, and develop a balanced exercise regimen. METHODS: A 1-year randomized controlled trial was conducted with physically underactive seniors in a multispecialty group practice. Changes in self-reported physical activity by group were evaluated using ANCOVA, controlling for age and sex. RESULTS: Of 173 randomized subjects, 164 (95%) completed the trial. Subjects were aged 65 to 90 years (M = 74, SD = 6); 66% were female. The intervention group increased estimated caloric expenditure by 487 calories/week in moderate (or greater) intensity activities (MET >/= 3.0; p <.001) and by 687 calories/week in physical activities of any intensity (p <.001). Control group changes were negligible. Between-group analyses found that the changes were significantly different in both measures (p values <.05). Overweight persons especially benefited from this program. The program was as effective for women, older adults (75+), and those who did not set aside time to exercise at baseline. CONCLUSIONS: The program led to meaningful physical activity increases. Individually tailored programs to encourage lifestyle changes in seniors may be effective and applicable to health care and community settings.

Repair of congenital pulmonary incompetence by bicuspidization of the pulmonary valve.

We report the successful repair of pulmonary incompetence in an adult due to the congenital absence of the posterior leaflet of the pulmonary valve. The repair consisted of bicuspidization of the pulmonary valve, which achieved competence and eliminated the symptoms and echocardiographic manifestations of right ventricular overload while preserving the native valve.

Intraoperative angiography during minimally invasive direct coronary artery bypass operations.

BACKGROUND: The technical demands of beating heart operations raise concerns about anastomotic patency. This feasibility study tested the usefulness of intraoperative angiography during minimally invasive direct coronary artery bypass grafting (MIDCABG). METHODS: Ten patients underwent intraoperative angiography of the internal thoracic artery (ITA) after MIDCABG. Minimally invasive direct coronary artery bypass grafting was performed on a beating heart through the fourth or fifth intercostal space. Angiography was performed through the right or left femoral artery with a 7F introducer system placed before the operation. Views were obtained in the right and left anterior oblique and straight anterior projections. RESULTS: There were no deaths or intraoperative morbidities related to MIDCABG or angiography. Seven patients demonstrated widely patent MIDCABG anastomoses with obliteration of all intercostals, widely patent ITA pedicles, good distal runoff, and placement of the ITA into the proper native coronary artery. Two patients had revisions of their ITA pedicles, which on repeated angiography showed correction. One patient's procedure was converted to a sternotomy because of poor distal runoff and haziness at the level of the MIDCABG anastomosis. CONCLUSIONS: This feasibility study demonstrates the utility of intraoperative ITA angiography in identifying problems after MIDCABG. Intraoperative angiography may facilitate MIDCABG by documenting proper placement of conduits, obliteration of intercostal vessels, and patency of the MIDCABG anastomosis and ITA pedicle.

Echocardiographic recognition of partial papillary muscle rupture.

Acute papillary muscle rupture complicating acute myocardial infarction represents a potentially lethal complication of acute myocardial infarction. Survival depends on prompt recognition and institution of immediate medical and surgical therapy. We present two cases of partial papillary muscle rupture in the setting of acute myocardial infarction and describe the echocardiographic features that may allow early recognition of this condition before complete rupture.

The efficacy of head immobilization techniques during simulated vehicle motion.

STUDY DESIGN: Laboratory experiment. OBJECTIVE: To compare the efficacy of different head immobilization techniques during motion simulating ambulance transport. BACKGROUND: A significant number of neurologic injuries associated with cervical spine fractures arise or are aggravated during emergency extrication or patient transport. Previous studies have not addressed the effect of head immobilization on the passive motion that could occur across the neck during transport. METHODS: Three different head-immobilization methods were compared in six healthy young adults by using a computer-controlled moving platform to simulate the swaying and jarring movements that can occur during ambulance transport. In all tests, the trunk was secured by means of a commonly used "criss-cross" strapping technique. Efficacy of head immobilization was evaluated using measures of head motion and neck rotation. RESULTS: None of the three immobilization techniques was successful in eliminating head motion or neck rotation. Movement of the trunk contributed substantially to the lateral bending that occurred across the neck. A new product involving the placement of wedges underneath the head provided some small, but statistically significant improvements in fixation of the head to the fracture board; however, there was no improvement in terms of the relative motion occurring across the neck. CONCLUSIONS: Somewhat improved fixation of the head to the fracture board can be achieved by placing wedges under the head; however, the benefits of any fixation method, in terms of cervical spine immobilization, are likely to be limited unless the motion of the trunk is also controlled effectively. Future research and development should address techniques to better control head and trunk motion.

Psychosocial sequelae of motor vehicle collisions: a follow-up study.

One-hundred-and-forty-nine motor vehicle collision trauma victims were interviewed one year after discharge from a Regional Trauma Unit. Follow-up data indicated major post trauma problems such depression, anxiety, family stress, financial problems and driving fears. Almost 40% reported drinking driving after the crash with a greater proportion of alcohol (blood alcohol content) positive drivers engaging in drinking driving than blood alcohol content negative drivers. Notably, almost 16% of the blood alcohol content positive and 13% of the blood alcohol content negative reported involvement in another crash in the year since discharge.

Psychosocial characteristics of alcohol-involved and nonalcohol-involved seriously injured drivers.

This study compared two groups of alcohol-positive and alcohol-negative, seriously injured, crash-involved drivers on demographics, personality characteristics, driving-related attitudes, prior driving history, lifestyle, substance use, and antecedent driver condition. The study sample was drawn from motor vehicle accident admissions to the Sunnybrook Health Science Centre Regional Trauma Unit. One hundred and six interviews were completed between August 1986 and November 1989, with blood alcohol concentration (BAC) data available for 96 drivers. These data suggest no driving-related attitude differences between the two groups. Self-reported driving histories indicated significantly fewer graduates of driving schools and more licence suspensions for the BAC-positive group. The only consistently significant differences were found for the drinking-related variables, with a greater percentage of the BAC-positive group reporting: lower age of first intoxication; a greater self-perceived drinking problem; a greater frequency of intoxication in the month before the accident; and greater self-reported drinking-driving in the month before the accident. Principal-components factor analysis revealed a four-factor solution labelled: Alcohol Use, Deviant/Illicit Drug Use, Aggression, and Neuroticism. Alcohol Use was the only factor found to contribute substantially to the discriminant function, together with the job-related stress item. These data suggest that seriously injured, alcohol-positive and alcohol-negative crashed drivers are similar except that the alcohol-positive drivers show more signs of an alcohol problem.

Injuries missed during initial assessment of blunt trauma patients.

OBJECTIVE: To determine the incidence and clinical significance of undiagnosed injuries in blunt trauma patients at our institution. DESIGN: Retrospective analysis of blunt trauma admissions over a 1-year period. Missed injury (MI) was defined as any injury recorded after the initial 24 hours. RESULTS: Of 432 patients studied, 59 (13.6%) had MI. Fractures were the most common MI. Thirty-five percent of MI were detected during repeated physical examination and 28% after patients were conscious and able to voice concerns. CONCLUSION: Over 10% of all blunt trauma patients had undiagnosed injuries. Forty percent of the MI had clinical implications. The most effective method of diagnosis consists of repeated clinical assessments. Special attention should be focused on patients with severe anatomical injuries, obtunded or intubated.

Early identification of high-risk patients using the "estimated" injury severity score and age.

A prospective study was undertaken over a 2 1/2 year period (July 1, 1985-December 31, 1987) to determine the value of a prospective anatomical severity score ["Estimated" Injury Severity Score (EISS)], in combination with age, for early risk assessment. Five hundred ninety-two blunt trauma patients were used to develop a predictive model of mortality through a logistic regression. The model was validated using 216 patients; a high degree of agreement (Kappa 0.73) was found. When isolated head injuries were removed from the model and validation groups, the Kappa increased to 0.80. Prospective anatomical scoring in combination with age may help to identify high-risk trauma patients early during their care.

Alcohol and drug use among motor vehicle collision victims admitted to a regional trauma unit: demographic, injury, and crash characteristics.

This study examined the incidence of alcohol and drugs in a sample of seriously injured motor vehicle collision victims, and differences related to pre-crash use of alcohol and/or other drugs on demographic variables, injury severity measures, and crash variables. The sample selected were all motor vehicle collision admissions to the Regional Trauma Unit at the Sunnybrook Health Science Centre in Toronto, Ontario, over a 37-month period (N = 854). Prospective demographic and injury-related information were collected from hospital charts, and crash data were collected from motor vehicle collision police reports. Blood samples were routinely collected on admission and tested for blood alcohol concentration (BAC). We found 32.0% of the BAC-tested motor vehicle collision admissions and 35.5% of drivers tested positive for blood alcohol. The drivers' mean BAC on admission was found to be 145.2 mg/100 ml, and the mean estimated BAC at crash time was 181 mg/100 ml. Drug screens were performed on a two-year subsample (n = 474), of whom 339 were drivers. Drug screens revealed that 41.3% of drivers tested positive for other drugs in body fluids, and 16.5% were positive for alcohol in combination with other drugs. Other than alcohol, the drugs most frequently detected in the drivers were cannabinoids (13.9%), benzodiazepines (12.4%), and cocaine (5.3%). Investigation of differences on demographic, injury, and crash characteristics related to precrash use of alcohol and/or drugs yielded significant findings. In the drug screened sample we found sex, admission type, and occupant status were related to precrash alcohol use. Also, use of drugs was found to interact with admission type and mean BAC on admission. Elapsed time was found to be significantly different for BAC by other drug use, with a greater length of elapsed time found for the subjects testing other drug positive but BAC negative. We found that BAC-positive drug-screened drivers were significantly more likely to be male, involved in a single-vehicle collision, not wearing a seat belt, ejected from the vehicle, and travelling at higher speeds than BAC negative drivers. No significant differences were found between BAC and/or other drug use on injury severity measures.

Blunt abdominal trauma.

Assessment and management of patients with blunt abdominal trauma remains a challenge for emergency physicians. The spectrum of injury ranges from the trivial to the catastrophic and the initial assessment, resuscitation, and investigation of patients with abdominal trauma must be individualized. This article covers the important aspects of patient history and physical examination and addresses the relevant investigative tools available. An approach to the assessment of patients with abdominal trauma is provided; the goal is to diagnose significant injuries as soon as possible and avoid the pitfall of a delayed or missed diagnosis.

A retrospective review of the relationship between facial fractures, head injuries, and cervical spine injuries.

Facial fractures are common in the multiply-traumatized patient, and the results of previous studies that have examined the relationship between facial fractures, cervical spine injuries, and head injuries have produced conflicting results. A retrospective review of 1,050 blunt-trauma patients during a 40-month period at a regional trauma unit revealed 168 patients with facial fractures. The average injury severity score (ISS) of these patients with facial fractures was 31 compared with an average ISS of 25.6 for the entire group. There were 266 facial fractures in these 168 patients: mandible (n = 72), maxilla (n = 74), zygoma (n = 52), orbital (n = 46), nasoethmoidal (n = 20), and frontal (n = 2). There were seven (4%) cervical spine injuries, three of which were atlanto-occipital subluxations in patients who ultimately died. Of the four surviving patients, one had a cord injury. In contrast, 145 (85%) showed evidence of head injuries; 64 (38%) of these head injuries were serious and 17 of these patients required craniotomy. The relationship of facial fractures and cervical spine injuries may be over emphasized; head injuries, although frequently minor, are much more commonly associated with facial fractures.

Two cases of accidental immersion hypothermia with different outcomes under identical conditions.

Two cases of accidental immersion hypothermia are presented, both occurring during the same aircraft ditching. One victim survived while the other patient died despite identical immersion time and environmental conditions. Pertinent literature is reviewed to attempt to explain the different patient outcomes. The most important discriminating factor appears to be skinfold thickness, which reflects body fat.

Implementing the Medicare electronic remittance advice.

Some hospitals have delayed converting to the electronic remittance advice recently implemented by the Health Care Financing Administration because the process is unfamiliar and because the electronic data interchange (EDI) translation software is expensive. However, the University of Pittsburgh Medical Center (UPMC) found that it could begin to reap the benefits of EDI technology by using existing software and hardware along with a common-sense approach to implementation. As a result, UPMC has begun an organizationwide EDI initiative designed to reduce costs and improve cash flow.

Air versus land transport of the critically injured patient.

Trauma patients frequently require transport from the hospital to which they are admitted initially to a trauma unit for further assessment and management. Canada's geography and demography provide unique challenges when transporting the severely injured patient by air or land. The author describes and compares air and land transport for the trauma patient. These complementary modes of transport are an integral part of a comprehensive trauma system.

Early experience with simulated trauma resuscitation.

Although trauma resuscitation is best taught through direct exposure with hands-on experience, the opportunities for this type of teaching in Canada are limited by the relatively low incidence of serious injury and the consolidation of trauma care to a small number of centres. Simulators have been used extensively outside the health care environment and more recently have been used by anesthetists to simulate intraoperative crises. In this paper early experience using a realistic mannequin, controlled by a remote computer, that simulates a variety of physiologic and injury specific variables is presented. The resource implications of simulated resuscitation are reviewed, including one-time and operating costs. Simulated trauma resuscitation may be an educational alternative to "real-life" trauma resuscitation, but careful evaluation of the benefits and resource implications of this type of teaching through well-designed research studies will be important.