Septic shock and multiple organ failure after hematopoietic stem cell transplantation: treatment with recombinant human activated protein C

Severe sepsis with multiple organ failure after hematopoietic stem cell transplantation (HSCT) results in extremely high morbidity and mortality. Recent studies have highlighted the importance of sepsis-induced activation of the coagulation system in the pathophysiology of severe sepsis. Activated protein C is an important modulator of coagulation and inflammatory derangements during severe sepsis. Low levels of protein C occur in severe sepsis and are predictive of poor outcome. Recombinant human activated protein C (drotrecogin alfa (activated)) was recently approved by the Food and Drug Administration (FDA) for severe sepsis. The phase III trial that resulted in the approval of this agent, however, enrolled a general sepsis population and excluded patients undergoing HSCT. We report a case of fulminant septic shock and multiple organ failure after HSCT that was treated with drotrecogin alfa (activated) in addition to standard therapy, and recovered. The high mortality rates of patients who develop severe sepsis after HSCT demand that new avenues of treatment be considered for this very high-risk patient population. This case illustrates the potential application of a novel therapeutic approach. Clinical trials are warranted to further investigate the safety and efficacy of drotrecogin alfa (activated) in patients with severe sepsis after HSCT.     

Finger pulley injuries in extreme rock climbers: depiction with dynamic US

PURPOSE: To determine the ability of dynamic ultrasonography (US) to depict finger pulley injuries in extreme rock climbers. MATERIALS AND METHODS: Sixty-four extreme rock climbers (climbing levels 8-11 on a scale ranging from 1 to 11; Union Internationale des Associations d'Alpinisme) with finger injuries (75 symptomatic and 181 asymptomatic fingers) were examined by using US, with the transducer operating at 12 MHz. The distance between the flexor tendon and phalanx was evaluated in extension and forced flexion at the level of the A2 and A4 annular pulleys as an indicator of tendon bowstringing. A distance between the flexor tendon and phalanx greater than 1.0 mm was interpreted as positive for a pulley injury. US findings were compared with those of magnetic resonance imaging. Surgical correlation was available in seven cases. Statistical analysis was performed by using analysis of variance, the Student t test, and the Bonferroni method. RESULTS: US depicted 16 (100%) of 16 complete A2 pulley ruptures, nine (100%) of nine complete A4 pulley ruptures, six (86%) of seven surgically proved complete combined A2 and A3 pulley ruptures, and 15 (100%) of 15 incomplete A2 pulley ruptures. Measurement of distance between the flexor tendon and phalanx was significantly different among patient subsets without pulley ruptures and those with incomplete, complete, or complete combined pulley ruptures (P <.001). The sensitivity of US for depiction of finger pulley injuries was 98%, and specificity was 100%. CONCLUSION: Dynamic US allows excellent depiction of finger pulley injuries in extreme rock climbers.     

Percutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intravenous liposomal doxorubicin in a rat breast tumor model

PURPOSE: To determine whether a combination of intravenous liposomal doxorubicin and radio-frequency (RF) ablation increases tumor destruction compared with RF alone in an animal tumor model. MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.4-1.8-cm- diameter nodules were implanted subcutaneously in 132 female Fischer rats. Initially, tumors were treated with (a) conventional, monopolar RF (mean, 250 mA +/- 25 [SD] at 70 degrees C +/- 1 for 5 minutes) ablation alone, (b) RF ablation followed by intravenous administration of 1 mg of liposomal doxorubicin, (c) RF ablation followed by intravenous administration of 1 mg of empty liposomes, (d) RF ablation and direct intratumoral administration of liposomal doxorubicin, or (e) no treatment. Subsequently, the dose (0.06-2.00 mg) of liposomal doxorubicin, the timing of administration (3 days before to 3 days after RF ablation), and the time of pathologic examination (0-72 hours after treatment) were varied. RESULTS: Mean coagulation diameter for treated tumors follows: 6.7 mm +/- 0.6, RF ablation alone; 11.1 mm +/- 1.5, RF ablation and intravenous administration of empty liposomes (P <.05, compared with RF ablation alone); and 8.4 mm +/- 1.1, RF ablation with intratumoral administration of liposomal doxorubicin (P <.05, compared with RF ablation alone). Maximal increased mean coagulation diameter (13.1 mm +/- 1.5) was observed with a combination of liposomal doxorubicin and RF ablation (P <.001, for all comparisons). The increased coagulation for combination therapy developed over 48 hours after therapy. Coagulation diameter did not vary with the doxorubicin concentration range and was not dependent on the timing of administration of liposomal doxorubicin from 3 days before to 24 hours after RF ablation. CONCLUSION: Intravenous administration of liposomal doxorubicin can improve RF ablation, since it increases coagulation diameter in solid tumors compared with RF ablation alone or a combination of RF ablation with administration of empty liposomes.     

Specificity of mammography and US in the evaluation of a palpable abnormality: retrospective review

PURPOSE: To determine the number of patients who received a diagnosis of breast cancer after having an area of clinical concern at presentation and combined negative mammographic and ultrasonographic (US) findings. MATERIALS AND METHODS: During a 4-year period, 829 patients with a palpable abnormality at presentation and combined negative mammographic and US findings were identified. The number of women who went on to receive a diagnosis of breast cancer was determined retrospectively. The authors searched the breast imaging database and the pathology database, sent a contact letter to the referring physicians, and linked their data to the State Cancer Registry. They also analyzed the breast parenchymal density among all patients who had more than 2 years of follow-up. RESULTS: Of the 829 women, 374 had follow-up information. Two-hundred thirty-three patients had negative imaging findings with more than 2 years of follow-up. The other 141 women were presumed to be cancer free, as they were not identified by the State Cancer Registry. Six (2.6%) of the 233 women had a diagnosis of breast cancer in the area of the palpable abnormality. The six cancers were diagnosed among the 156 women who had radiographically dense breast tissue (Breast Imaging Reporting and Data System category 3 or 4). Among the 77 women with predominantly fatty tissues, no cancers were diagnosed. CONCLUSION: A negative mammographic and US finding of a palpable abnormality does not exclude breast cancer, but the likelihood of breast cancer is low, approximately 2.6%-2.7%. It may be higher if the breast tissues are dense and lower if they are predominantly fatty.     

The continuing unethical conduct of underpowered clinical trials

Scott D. Halpern, MSCE; Jason H. T. Karlawish, MD; Jesse A. Berlin, ScD

JAMA. 2002;288:358-362.

Despite long-standing critiques of the conduct of underpowered clinicaltrials, the practice not only remains widespread, but also has garnered increasingsupport. Patients and healthy volunteers continue to participate in researchthat may be of limited clinical value, and authors recently have offered 2related arguments to support the validity and value of underpowered clinicaltrials: that meta-analysis may "save" small studies by providing a means tocombine the results with those of other similar studies to enable estimatesof an intervention's efficacy, and that although small studies may not providea good basis for testing hypotheses, they may provide valuable estimates oftreatment effects using confidence intervals. In this article, we examinethese arguments in light of the distinctive moral issues associated with theconduct of underpowered trials, the disclosures that are owed to potentialparticipants in underpowered trials so they may make autonomous enrollmentdecisions, and the circumstances in which the prospects for future meta-analysesmay justify individually underpowered trials. We conclude that underpoweredtrials are ethical in only 2 situations: small trials of interventions forrare diseases in which investigators document explicit plans for includingtheir results with those of similar trials in a prospective meta-analysis,and early-phase trials in the development of drugs or devices, provided theyare adequately powered for defined purposes other than randomized treatmentcomparisons. In both cases, investigators must inform prospective subjectsthat their participation may only indirectly contribute to future health carebenefits.

     

Interventional radiologic procedures: patient anxiety, perception of pain, understanding of procedure, and satisfaction with medication--a prospective study

PURPOSE: To prospectively assess patient anxiety, understanding of the procedure being performed, perception of pain level, and satisfaction with medication given for a variety of diagnostic and therapeutic vascular and visceral (nonvascular) interventional procedures. MATERIALS AND METHODS: The authors interviewed 204 patients before and after they underwent an interventional radiologic procedure. Patients responded to a series of questions by using a visual analog scale. Patients were grouped according to (a) their level of experience with the procedure and (b) the type of procedure performed (diagnostic or therapeutic visceral procedure or diagnostic or therapeutic vascular procedure). RESULTS: Patients who had previous experience with a procedure, whether visceral or vascular, were less anxious, had more understanding, and anticipated less pain than did those who did not have experience with a procedure. Patients who had only local anesthesia for visceral biopsy experienced greater pain than did those who had both local and intravenous anesthesia. Satisfaction scores, however, were similar throughout all groups. CONCLUSION: Patients have a moderate amount of anxiety about interventional procedures and anticipate some discomfort. Most patients have a high level of satisfaction despite the amount of pain they experience during the procedure. Patients experienced with a procedure tend to have a greater understanding of the procedure and less anxiety.     

Inferior vena caval filters: review of a 26-year single-center clinical experience

PURPOSE: To review a 26-year single-center clinical experience with inferior vena caval filters. MATERIALS AND METHODS: During 1973-1998, 1,765 filters were implanted in 1,731 patients. Hospital files were reviewed, and data were collected about the indications, safety, effectiveness, numbers, and types of caval filters. Fatal post-filter pulmonary embolism (PE) was considered the primary outcome. Morbidity and mortality were determined as secondary outcomes. Survival and morbidity-free survival curves were calculated. RESULTS: The prevalence of observed post-filter PE was 5.6%. It was fatal in 3.7% of patients. In most patients, fatal PE occurred soon after filter insertion (median, 4.0 days; 95% CI: 2.2, 5.8 days). Major complications occurred in 0.3% of procedures. The prevalence of observed post-filter caval thrombosis was 2.7%. The 30-day mortality rate was 17.0% overall, higher among patients with neoplasms (19.5%) as compared with those without neoplasms (14.3%; P =.004). Filter efficacy and associated morbidity were not different in 46 patients with suprarenal filters. The rate of filters placed for prophylaxis was 4.7% overall and increased to 16.4% in 1998. From 1980 to 1996, there was a fivefold increase in the number of caval filter implants. In recent years, more filters were implanted in younger patients. CONCLUSION: Inferior vena caval filters provide protection from life-threatening PE, with minimal morbidity.