This Week in the Journal

February 21, 2002

Mild Therapeutic Hypothermia after Cardiac Arrest

Cerebral injury and associated cognitive dysfunction are commonafter sustained cardiac arrest. In this study, mild therapeutichypothermia was compared with normothermia in patients who hadbeen resuscitated after cardiac arrest due to ventricular fibrillation.A favorable neurologic outcome was significantly more frequentin the group treated with hypothermia.

These results, in conjunction with those of another study inthis issue, suggest that mild therapeutic hypothermia may havea substantial benefit in patients who have been resuscitatedafter cardiac arrest and that this approach should now be consideredin the care of such patients.

Related Editorial

Hypothermia in the Treatment of Comatose Survivors of Cardiac Arrest

Patients who remain unconscious after resuscitation from cardiacarrest outside the hospital have a poor prognosis. In this trial,77 patients were assigned to treatment with moderate inducedhypothermia or normothermia. Survival to hospital dischargewith good neurologic recovery was more frequent in the hypothermiagroup than in the normothermia group.

This study on its own would be regarded as preliminary, becauseit included only a small number of patients and had other importantlimitations. However, when considered in conjunction with theHypothermia after Cardiac Arrest Study reported in this issueof the Journal, it indicates that moderate hypothermia may improveoutcome in this otherwise ominous condition.

Related Editorial

Prognosis in Monoclonal Gammopathy of Undetermined Significance

A monoclonal gammopathy of undetermined significance (MGUS)is diagnosed when there is serum monoclonal protein at a concentrationof 3 g per deciliter or less in the absence of evidence of multiplemyeloma or a related disorder. The condition is not rare inpeople over the age of 50 years and may progress to full-blownmultiple myeloma over a period of years. This study of almost1400 patients, who were followed for up to 35 years, definesthe risk of progression to multiple myeloma and the importantpredictors of progression.

It is impossible to tell whether MGUS is an innocent proliferationof a clone of B cells that produce a telltale monoclonal immunoglobulin,or the sinister precursor of multiple myeloma, amyloidosis,or a B-cell lymphoma. This comprehensive study of a large numberof patients with MGUS provides clinically valuable informationabout the risk of progression to multiple myeloma and relateddisorders and about prognostic factors.

Leptin Replacement in the Treatment of Lipodystrophy

Patients with severe lipodystrophy have a marked deficiencyof the adipocyte hormone leptin. In this study nine female patientswith marked lipodystrophy, hypertriglyceridemia, hepatic steatosis,and diabetes (in eight patients) received escalating doses ofrecombinant methionyl human leptin for four months. Leptin-replacementtherapy improved glycemic control, lowered triglyceride levels,and decreased daily caloric intake and the resting metabolicrate.

Leptin deficiency may be a major factor in the insulin resistanceand other metabolic abnormalities that characterize severe lipodystrophy.

Medical Progress: Improving Long-Term Outcomes after Renal Transplantation

This article provides a comprehensive, up-to-date review ofmethods to prevent early and late renal-allograft loss and toimprove long-term outcomes in patients. The authors focus particularattention on the problem of late graft loss and discuss currentantirejection therapy, including calcineurin blockers such ascyclosporine and tacrolimus, the interleukin-2 signal-transductioninhibitor sirolimus, and the purine-synthesis inhibitor mycophenolatemofetil, which inhibits the proliferation of T cells and B cells.

Drug Therapy for Obesity

The most common nutritional disorders in the United States areoverweight and obesity. This review discusses the treatmentof overweight and obesity as chronic conditions that requirea combined approach of behavioral therapy, exercise, dietarychanges, and — in certain cases — medication. Theauthors consider the three classes of weight-loss drugs: thosethat suppress appetite, those that decrease nutrient absorption,and those that increase energy expenditure. Currently availableand soon-to-be-released drugs are discussed.

Weight-loss medications are best used as an adjunct in patientsat substantial medical risk because of obesity in whom nonpharmacologictherapy has failed.

Clinical Implications of Basic Research: New Therapeutic Targets in Crohn's Disease

NOD2, a gene conferring susceptibility to Crohn's disease, hasbeen identified on chromosome 16. Homozygosity for a mutationthat truncates the gene increases the risk of Crohn's diseaseby a factor of 20 to 40. No such mutations have been found inpatients with ulcerative colitis. NOD2 has a role in apoptosisand in the recognition of microbial endotoxins.

The discovery of truncating mutations of NOD2 in Crohn's diseaseis an important advance. It opens new possibilities for screeningfor familial and sporadic cases and suggests avenues for treatment.

Sounding Board: Blood and Disaster

Almost immediately after the attacks that struck New York Cityand Washington, D.C., on September 11, 2001, the federal governmentand the American Red Cross issued an appeal for blood donors.Nationwide, more than 1 million prospective donors respondedto the call and almost 500,000 units of blood were collectedfor the victims. Yet only 258 units were used. Many of the collectedunits were unusable.

After a disaster, mass appeals for blood donors may be unnecessary.Blood banks in virtually all urban centers have enough bloodon hand for at least the first three days of an emergency, andthis supply can quickly be supplemented by stocks in neighboringcities. Disaster planning should include means of coordinatingblood supplies.

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