The need for unique risk adjustment for surgical site infections at a high-volume, tertiary care center with inherent high-risk colorectal procedures.

BACKGROUND: The aim of the present study was to create a unique risk adjustment model for surgical site infection (SSI) in patients who underwent colorectal surgery (CRS) at the Cleveland Clinic (CC) with inherent high risk factors by using a nationwide database. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify patients who underwent CRS between 2005 and 2010. Initially, CC cases were identified from all NSQIP data according to case identifier and separated from the other NSQIP centers. Demographics, comorbidities, and outcomes were compared. Logistic regression analyses were used to assess the association between SSI and center-related factors. RESULTS: A total of 70,536 patients met the inclusion criteria and underwent CRS, 1090 patients (1.5%) at the CC and 69,446 patients (98.5%) at other centers. Male gender, work-relative value unit, diagnosis of inflammatory bowel disease, pouch formation, open surgery, steroid use, and preoperative radiotherapy rates were significantly higher in the CC cases. Overall morbidity and individual postoperative complication rates were found to be similar in the CC and other centers except for the following: organ-space SSI and sepsis rates (higher in the CC cases); and pneumonia and ventilator dependency rates (higher in the other centers). After covariate adjustment, the estimated degree of difference between the CC and other institutions with respect to organ-space SSI was reduced (OR 1.38, 95% CI 1.08-1.77). CONCLUSIONS: The unique risk adjustment strategy may provide center-specific comprehensive analysis, especially for hospitals that perform inherently high-risk procedures. Higher surgical complexity may be the reason for increased SSI rates in the NSQIP at tertiary care centers.

Advancing pharmacovigilance through academic-legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis-a Research on Adverse Drug Events and Reports (RADAR) report.

OBJECTIVE: To compare and contrast three databases, that is, The International Centre for Nephrogenic Systemic Fibrosis Registry (ICNSFR), the Food and Drug Administration Adverse Event Reporting System (FAERS) and a legal data set, through pharmacovigilance and to evaluate international nephrogenic systemic fibrosis (NSF) safety efforts. METHODS: The Research on Adverse Drug events And Reports methodology was used for assessment-the FAERS (through June 2009), ICNSFR and the legal data set (January 2002 to December 2010). Safety information was obtained from the European Medicines Agency, the Danish Medicine Agency and the Food and Drug Administration. RESULTS: The FAERS encompassed the largest number (n = 1395) of NSF reports. The ICNSFR contained the most complete (n = 335, 100%) histopathological data. A total of 382 individual biopsy-proven, product-specific NSF cases were analysed from the legal data set. 76.2% (291/382) identified exposure to gadodiamide, of which 67.7% (197/291) were unconfounded. Additionally, 40.1% (153/382) of cases involved gadopentetate dimeglumine, of which 48.4% (74/153) were unconfounded, while gadoversetamide was identified in 7.3% (28/382) of which 28.6% (8/28) were unconfounded. Some cases involved gadobenate dimeglumine or gadoteridol, 5.8% (22/382), all of which were confounded. The mean number of exposures to gadolinium-based contrast agents (GBCAs) was gadodiamide (3), gadopentetate dimeglumine (5) and gadoversetamide (2). Of the 279 unconfounded cases, all involved a linear-structured GBCA. 205 (73.5%) were a non-ionic GBCA while 74 (26.5%) were an ionic GBCA. CONCLUSION: Clinical and legal databases exhibit unique characteristics that prove complementary in safety evaluations. Use of the legal data set allowed the identification of the most commonly implicated GBCA. ADVANCES IN KNOWLEDGE: This article is the first to demonstrate explicitly the utility of a legal data set to pharmacovigilance research.

Melanoma associated with tumour necrosis factor-α inhibitors: a Research on Adverse Drug events And Reports (RADAR) project.

BACKGROUND: Tumour necrosis factor-α inhibitors (TNFαIs) are used for treatment of inflammatory disorders. There is evidence linking these agents with occurrence of malignancies. For four out of five TNFαIs the Food and Drug Administration (FDA) label states, 'melanoma has been reported in patients treated with these agents'. OBJECTIVES: To determine whether a statistically significant association exists between administration of TNFαIs and development of malignant melanoma. METHODS: We searched the FDA Adverse Event Reporting System (FAERS) database for terms related to melanoma and TNFαIs for detection of safety signals. We also searched a large urban academic electronic medical record (EMR) database for which we calculated the relative risk (RR) of melanoma in subjects exposed to TNFαIs vs. nonexposed subjects. RESULTS: There were 972 reports of melanoma associated with a TNFαI identified in the FAERS database, with 69 reports among individuals using more than one TNFαI. A safety signal was detected for infliximab, golimumab, etanercept and adalimumab, but not certolizumab pegol. For TNFαIs as a class of drugs, a safety signal was detectable in the FAERS database, and RR was significant in the EMR database. For the EMR cohort, 6045 patients were exposed to TNFαIs and 35 cases of melanoma were detected. Significance for RR was detected for adalimumab (RR 1·8, P = 0·02) and etanercept (RR 2·35, P = 0·0004 < 0·001). CONCLUSIONS: We identified a significant association between exposure to TNFαIs and malignant melanoma in two different analyses. Our findings add to existing evidence linking these agents with the occurrence of malignant melanoma. Additional investigations are required to explore this association further along with the risk of melanoma with TNFαI therapy.

Gender differences in mortality, quality of life and function after restorative procedures for rectal cancer.

AIM: Studies investigating the functional outcome after restorative surgery for rectal cancer have mainly focused on the effect of different surgical techniques on bowel habit or sexual activity at a single time-point. The aim of this study was to assess, longitudinally, the effect of rectal cancer treatment on bowel function, quality of life and sexual activity. METHOD: The study parameters were assessed using self-administered questionnaires, including the Short Form 36 (SF-36), repeatedly, over a 5-year period. Patient details were obtained from the Cleveland Clinic prospective database. RESULTS: There were 260 (186 male) patients. The mean ages of male and female patients at the time of surgery were 60.5 and 57.5 years, respectively. There was no significant difference in comorbidity or stage between the groups. Women had a better overall survival. More women than men had postoperative radiation and perioperative blood transfusions. Men had a higher percentage of hand-sewn anastomoses (23.9%vs 10.8%, P = 0.018), but there was no overall difference in the mean level of anastomosis (2.3 cm vs 1.9 cm, P = 0.38). Men had worse nocturnal bowel function, more incontinence and a poorer mental component score on the SF-36. Pad use increased over time to a greater degree in women. Sexual activity, which was similar in men and women at baseline, had fallen at 5 years in both genders. CONCLUSION: After restorative resection for rectal cancer, bowel function is worse in men than in women, especially night evacuation at 3 and 5 years postoperatively. Sexual function in both genders declines sharply initially within 1 year postoperatively and more gradually over 5 years.

Morbidity and mortality of the Hartmann procedure for diverticular disease over 18 years in a single institution.

AIM: Hartmann's procedure for perforated diverticulitis is associated with substantial morbidity and mortality. This study analyses factors associated with morbidity/mortality and possible changes over time. METHOD: Patients treated by urgent Hartmann's procedure for perforated diverticulitis between 1992 and 2010 were studied, and information was collected on age, sex, perioperative details, 30-day morbidity and mortality recorded in an institutional review board approved database supplemented by chart review. Patients were divided into four groups based on the year of surgery. Univariate and multivariate logistic regression analysis was performed to identify risk factors associated with morbidity and mortality. RESULTS: In all, 199 patients (51% female, mean age 65 years, mean body mass index 28 kg/m(2)) were identified. The American Society of Anesthesiologists (ASA) score was 4 in 30% of patients and Hinchey Stage IV in 16%. The mean length of stay was 12.5 ± 10 days. Mortality was 15% and did not change significantly over time. Overall morbidity was 52% and significantly increased over time on univariate analysis (P = 0.007) but not on multivariate analysis (P = 0.11). Independent predictors of morbidity on multivariate analysis were Hinchey IV (P < 0.001) and hypoproteinaemia (P = 0.001). Independent predictors for mortality were ASA > 3 (P = 0.01), abnormal creatinine (P = 0.007), steroid use (P = 0.007), Hinchey IV (P = 0.032), low albumin (P < 0.001) and low body mass index (P = 0.001). CONCLUSION: Mortality after Hartmann's procedure for perforated diverticulitis has not decreased during the last 18 years. Morbidity has actually increased over time although this is related to increased disease severity and comorbidity. Future efforts should focus on the identification of patient subgroups benefiting from earlier elective surgery and alternative surgical approaches when perforated diverticulitis does occur.

Surgery of recurrent parastomal hernia: direct repair or relocation?

PURPOSE: Parastomal hernia is a common late complication after stoma creation. The management options are many; unfortunately, most literature suggests unsatisfactory results. There are few studies comparing the outcomes after repair of parastomal hernias especially in recurrent cases, and the results are controversial. The aim of this study was to compare outcomes after repair of recurrent parastomal hernias between direct repair (DR) and relocation (RL). METHOD: We performed a retrospective chart review of patients who underwent direct repair or RL for recurrent parastomal hernia during the period between 1990 and 2005. Perioperative data and re-recurrence rates were obtained and analysed with appropriate statistical methods. RESULTS: With mean follow-up time of 2 years, 50 operations were available for evaluation; 27 (54%) DR and 23 (46%) RL [five same-side RL (SSRL) and 18 opposite-side RL (OSRL)]. There were no deaths and there were similar complication rates between groups. Four of five (80%) SSRL had a re-recurrent parastomal hernia. Considering only DR with OSRL, although OSRL had longer operative time and hospital stay than DR, the re-recurrence rate was lower (38%vs 74%; P = 0.02). However, with Kaplan-Meier calculated and longer predicted follow-up time, re-recurrence rates were similar (Log rank P = 0.09). CONCLUSION: Recurrent parastomal hernia repair is associated with high re-recurrence rates.OSRL seems to have promising short-term outcomes; however, whether these results hold up long-term remains unclear. Therefore, larger cohorts of patients with longer follow-up or prospective randomized trials are needed.

Combined surgery in pelvic organ prolapse is safe and effective.

OBJECTIVE: In women, rectal prolapse is often accompanied by other signs of generalized pelvic floor weakness including uterine and bladder prolapse. The purpose of this study was to compare whether there are differences in outcomes of rectal prolapse surgery between women having combined pelvic organ prolapse (POP) surgery with a urologist or urogynecologist (CS) vs those having abdominal rectal prolapse surgery alone (RP). METHOD: Charts were reviewed to collect perioperative data on those having surgery from 1995 to 2001. Phone surveys were conducted to obtain Cleveland Clinic Foundation (CCF) Incontinence score, Knowles-Eccersley-Scott-Symptom (KESS) Constipation Score, Short Form 36 (SF-36) quality of life score and recurrence rate. Appropriate statistical analysis was performed. RESULTS: Ninety-four operations were performed (23 CS and 71 RP). Forty-six (49%) could be contacted by phone. Mean follow-up was similar in both groups (CS 4.1 vs RP 3.6 years; P = 0.796). There were no significant differences between both groups regarding age, American Society of Anesthesiology classification Score, complications, length of hospital stay, CCF Incontinence score, KESS Constipation Score, SF-36 Score and recurrence rate of rectal prolapse. The operative time (CS 226 vs RP 122 min; P < 0.001) and blood loss (CS 377 vs RP 183 ml; P < 0.001) were significantly increased in the CS group. CONCLUSION: Combined surgery for POP is safe and effective when considering outcomes of rectal prolapse surgery. Therefore surgeons should not hesitate to address all pelvic floor issues during the same operation by working in partnership with the anterior pelvic floor colleagues.

Fever evaluations after colorectal surgery: identification of risk factors that increase yield and decrease cost.

PURPOSE: This study was designed to evaluate the yield and cost of fever evaluations in average-risk inpatients after elective colorectal surgery. METHODS: A 12-month, retrospective study was performed on patients who developed a postoperative fever > or = 38 degrees C after elective colorectal surgery. A positive fever evaluation was defined as a blood culture, urine culture, chest x-ray, or abdominal CT result that led to a change in patient management. Logistic regression, Fisher's exact test, and chi-squared test were used; odds ratios were calculated. RESULTS: Of 133 patients, 26 percent had a positive evaluation. Blood culture, urine culture, chest x-ray, and CT were positive in 3, 8, 7, and 46 percent, respectively. Risk factors for a positive fever evaluation were temperature > or = 38.5 degrees C, fever evaluation after postoperative Day 6, and a clinical manifestation of systemic inflammatory response syndrome other than fever (all, P < 0.01). The cost per positive fever evaluation for the entire group, patients with 2 risk factors, or patients with 3 risk factors was $5,600, $4,200, and $2,140, respectively. CONCLUSIONS: The current approach to fever evaluation after elective colorectal surgery is low yield and costly. High fever, late postoperative fever, and systemic inflammatory response syndrome are risk factors for a positive fever evaluation after colorectal surgery.

Crohn's disease: a patient's perspective.

AIM: As healthcare providers for Crohn's disease, we assume that we have a good understanding of the disease progression and its symptoms. The aim of this study was to gather information about what patients with Crohn's disease think are relevant to their symptoms and what helps them cope with this lifelong benign disease. MATERIALS AND METHODS: A questionnaire was sent to all patients with a diagnosis of Crohn's disease seen in the Digestive Disease Center in the last 5 years. The returned forms were downloaded into a database and sent for analysis. RESULTS: Sixty-two percent of respondents were female. One third were between the ages of 35 and 50 years. Seventy percent were married. Thirty-eight percent had a graduate degree, 19% were unemployed. Fifty percent still smoked, half of them less than one pack a day. Sixty-eight percent said that their symptoms affected work, and one fourth changed jobs due to this. Foods worsened symptoms in 60%, with a decrease in symptoms while on low fiber foods and white meats. Lifestyle change worsened symptoms in 66%. A change in the caregiver was not a significant stressor. More than half used Remicade, with one third stating that it was helpful. Eight percent had never used steroids. Alcohol increased symptoms in 40%. Factors that did not cause a significant change were children at any age, pregnancy, menopause, and hormone replacement therapy. Surgery caused half the patients to improve for many years, although one third felt a lowered self-esteem postoperatively. CONCLUSION: Patients with Crohn's disease should be managed in a more comprehensive manner to provide optimal care. Thus, a team approach that includes a dietician and counselor should be considered as an integral part of this team. This will allow patients to have enhanced skills to cope with changes in their symptoms, whether they are due to the disease itself or the changes in their routine.

Long-term outcome after laparoscopic and open surgery for rectal prolapse: a case-control study.

BACKGROUND: Laparoscopic repair (LR) of rectal prolapse is potentially associated with earlier recovery and lower perioperative morbidity, as compared with open transabdominal repair (OR). Data on the long-term recurrence rate and functional outcome are limited. METHODS: Perioperative data on rectal prolapse in relation to all LRs performed between December 1991 and April 2004 were prospectively collected. The LR patients were matched by age, gender, and procedure type with OR patients who underwent surgery during the same period. Patients with previous complex abdominal surgery or a body mass index exceeding 40 were excluded from the study. Data on recurrence rate, bowel habits, continence, and satisfaction scores were collected using a telephone survey. RESULTS: A total of 111 patients (age, 56.8 +/- 18.1 years; female, 87%) underwent attempted LR. An operative complication deferred repair in two cases. Among the 111 patients, 42 had posterior mesh fixation, and 67 had sutured rectopexy (32 patients with sigmoid colectomy for constipation). Eight patients (7.2%) had conversion to laparotomy. Matching was established for 86 patients. The LR patients had a shorter hospital stay (mean, 3.9 vs 6.0 days; p < 0.0001). The 30-day reoperation and readmission rates were similar for the two groups. The rates for recurrence requiring surgery were 9.3% for LR and 4.7% for OR (p = 0.39) during a mean follow-up period of 59 months. An additional seven patients in each group reported possible recurrence by telephone. Postoperatively, 35% of the LR patients and 53% of the OR patients experienced constipation (p = 0.09). Constipation was improved in 74% of the LR patients and 54% of the OR patients, and worsened, respectively, in 3% and 17% (p = 0.037). The postoperative incontinence rates were 30% for LR and 33% for OR (p = 0.83). Continence was improved in 48% of the LR patients and 35% of the OR patients, and worsened, respectively, in 9% and 18% (p = 0.22). The mean satisfaction rates for surgery (on a scale of 0 to 10) were 7.3 for the LR patients and 8.1 for the OR patients (p = 0.17). CONCLUSIONS: The hospital stay is shorter for LR than for OR. Both functional results and recurrent full-thickness rectal prolapse were similar for LR and OR during a mean follow-up period of 5 years.

Complex partial seizures of frontal lobe onset statistical analysis of ictal semiology.

OBJECTIVE: To identify the ictal semiology of complex partial seizures originating from the frontal lobe (FLCPS) and mesial temporal lobe (MTLE) in patients who became seizure free after surgery. METHODS: We analysed 149 seizures from 42 patients, 28 with MTLE (75 seizures) and 14 with FLCPS (74 seizures) seizure free for at least 1 year after surgery. Fifty-eight symptoms and signs were looked for in every seizure and their time of onset and ending noted. Statistical analysis was then used to define the frequency, time of onset and cluster analysis of these symptoms/signs. RESULTS: Epigastric aura was more frequent in MTLE while an aura of a general body sensation or indescribable feeling occurred only in FLCPS. Alimentary automatisms were more common and occurred earlier in MTLE (P<0.001). Perseverative automatisms, retching and vomiting occurred exclusively in MTLE while bicycling movements occurred only in FLCPS. Abdominal, psychic or olfactory aura followed by behavioural arrest, alimentary automatisms, repetitive distal upper extremity movements, complete loss of consciousness, looking around and whole body movements were typical of MTLE. Repetitive coarse upper extremity movements, complete loss of consciousness, complex motor and hypermotor activity were typical of FLCPS. CONCLUSION: The earliest symptoms and signs as well as their order of appearance allow one to distinguish between complex partial seizures arising from the frontal lobe and mesial temporal lobe.

Alterations in exhaled gas profile during allergen-induced asthmatic response.

The source of exhaled carbon monoxide (CO) and the relationship to airway inflammation are not clear. If CO is produced by the inflamed airway, we hypothesized that inflammation induced by allergen challenge would increase exhaled CO of atopic asthmatics. Eight atopic asthmatics underwent whole lung allergen challenge. CO, nitric oxide (NO), oxygen, and carbon dioxide (CO(2)) were measured simultaneously in exhaled breath which was collected into Mylar balloons before (baseline), immediately after, and at subsequent times after allergen. NO was higher in asthmatics than control subjects at baseline, increased further in seven of the eight asthmatics after allergen, and was inversely correlated to specific conductance. In contrast, exhaled CO of asthmatics was not higher than that of control individuals at baseline, decreased immediately after allergen, and returned to baseline levels during the late asthmatic response. Thus, allergen-induced airway inflammation did not lead to increased exhaled CO in asthma.

Typical and atypical chronic lymphocytic leukemia differ clinically and immunophenotypically.

We compared the features of 17 cases of atypical chronic lymphocytic leukemia (aCLL) with those of a clinical control group of 24 cases of CLL. Quantitative flow cytometric data, available for 12 cases, were compared with an immunophenotypic control group of 58 cases using a relative fluorescence indexfor CD5, CD23, CD79b, and surface immunoglobulin light chain (sIg). Compared with the clinical control group, patients with aCLL had a higher mean WBC count and a lower platelet count. Patients with aCLL had a significantly higher probability of disease progression. Compared with an immunophenotypic control group of 58 CLL cases, 12 cases of aCLL demonstrated significantly higher expression of CD23. There was no significant difference in expression of sIg, CD79b, or CD5 between the groups. CD38 expression was noted in only 1 (9%) of 11 tested cases; 2 (18%) of 11 cases had trisomy 12. aCLL can be distinguished from typical CLL morphologically, clinically, and immunophenotypically. Atypical morphologic features in CLL seem to be a marker of aggressive clinical behavior.

Repair of recurrent rectovaginal fistulas.

BACKGROUND: Recurrent rectovaginal fistulas (RRVFs) pose a challenging problem, which can be treated by different surgical procedures. We performed this study to determine the ultimate success rate of various repair techniques. METHODS: Using a standard data collection form, we retrospectively reviewed charts of patients treated for RRVF. RESULTS: Between 1991 and 2000, 57 procedures were performed in 35 women who presented with RRVF. Median follow-up was 4 months (interquartile range, 1,25). The causes of RRVF included obstetrical injury (n = 15), Crohn's disease (n = 12), fistula occurring after proctocolectomy with ileal pouch-anal anastomosis (for ulcerative colitis, n = 3; indeterminate colitis, n = 1; familial polyposis, n = 1), cryptoglandular disease (n = 2), and fistula occurring immediately after low anterior resection for rectal cancer (n = 1). The methods of repair used included mucosal advancement flap (n = 30), fistulotomy with overlapping sphincter repair (n = 14), rectal sleeve advancement (n = 3), fibrin glue (n = 1), proctectomy with colonic pull-through (n = 2), and ileal pouch revision (n = 6). Twenty-seven of 34 (79%) patients with adequate follow-up eventually healed after a median of 2 operations. Logistic regression was used to analyze outcome according to etiology of fistula, patient age, number of prior repairs, time interval between last repair and current repair, and presence of fecal diversion. Crohn's disease, the presence of a diverting stoma, and decreased time interval since prior repair were associated with a poorer outcome. CONCLUSIONS: Most RRVFs can be successfully repaired, although repeated operations may be necessary. Delaying repair may improve outcome.

Privately funded quality health care in India: a sustainable and equitable model.

OBJECTIVE: As the cost and degree of training necessary to provide state of the art health care has increased throughout the world, the present challenge in health care is to establish institutions that are financially sound and responsive to the dynamic needs of the communities in which they exist. As public funds have diminished, the role of the private sector in estabhshing innovative health care institutions has increased. SETTING AND STUDY PARTICIPANTS: This paper reviews the case of the LV Prasad Eye Institute (LVPEI), an ophthalmologic institute in Hyderabad, India, that is financially sound and medically vital. With an annual budget of US$3 million, 180 000 patients are seen and 23 000 surgeries are performed at the Institute and its satellites each year. MAIN MEASURES: The Institute provides patient care at a ratio of 1:1 non-paying to paying patients through fee cross-subsidization. The Institute uses a combination of financial modalities, including donations, grants and fees to administer its non-patient care programs. Non-clinical programs of the Institute include a paramedical training program and a fellowship in ophthalmology, an internationally accredited eye bank for the preservation of corneal tissues, a rural out-reach and education program, a basic science and epidemiology program that directs health policy activities of the Institute and a rehabilitation program for patients with incurable visual deficits. To evaluate its effectiveness, LVPEI uses quality improvement measures, including patient surveys, post-operative outcomes studies and service utlization reviews. CONCLUSION: This case report of a privately-funded medical institution describes a successful model through which high-quality, equitable health care can be provided in a developing country. The LVPEI's active program of quality management, its academic commitment and programmatic relevance to the needs of its community should be modularized and replicated to establish equitable, efficient and effective health care institutions in the developing world.

Extracorporeal liver perfusion using human and pig livers for acute liver failure.

BACKGROUND: Patients with fulminant hepatic failure (FHF) often die awaiting liver transplantation. Extracorporeal liver perfusion (ECLP) has been proposed as a method of "bridging" such patients to transplantation. We report the largest experience to date of ECLP using human and porcine livers in patients with acute liver failure. METHODS: Patients with FHF unlikely to survive without liver transplantation were identified. ECLP was performed with human or porcine livers. Patients underwent continuous perfusion until liver transplantation or withdrawal of support. Two perfusion circuits were used: direct perfusion of patient blood through the extracorporeal liver and indirect perfusion with a plasma filter between the patient and the liver. FINDINGS: Fourteen patients were treated with 16 livers in 18 perfusion circuits. Nine patients were successfully "bridged" to transplantation. ECLP stabilized intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Arterial ammonia levels fell from a median of 146 to 83 micromol/liter within 12 hr and this reduction was maintained at least 48 hr. Pig and human ECLP lowered ammonia levels equally. Serum bilirubin levels also fell from a median of 385 to 198 micromol/liter over the first 12 hr but the response was not sustained as well with porcine livers. There was no immunological benefit to using the the filtered perfusion circuit. INTERPRETATION: These data demonstrate that ECLP is safe and can provide metabolic support for comatose patients with fulminant hepatic failure for up to 5 days. While labor and resource intensive, this technology is available to centers caring for patients with acute liver failure and deserves wider evaluation and application.

Analysis of risk factors for myocardial infarction and cardiac mortality after major vascular surgery.

BACKGROUND: Patients undergoing vascular surgical procedures are at high risk for perioperative myocardial infarction (PMI). This study was undertaken to identify predictors of PMI and in-hospital death in major vascular surgical patients. METHODS: From the Vascular Surgery Registry (6,948 operations from January 1989 through June 1997) the authors identified 107 patients in whom PMI developed during the same hospital stay. Case-control patients (patients without PMI) were matched at a 1x:x1 ratio with index cases according to the type of surgery, gender, patient age, and year of surgery. The authors analyzed data regarding preoperative cardiac disease and surgical and anesthetic factors to study association with PMI and cardiac death. RESULTS: By using univariable analysis the authors identified the following predictors of PMI: valvular disease (P = 0.007), previous congestive heart failure (P = 0.04), emergency surgery (P = 0.02), general anesthesia (P = 0.03), preoperative history of coronary artery disease (P = 0.001), preoperative treatment with beta-blockers (P = 0.003), lower preoperative (P = 0.03) and postoperative (P = 0.002) hemoglobin concentrations, increased bleeding rate (as assessed from increased cell salvage; P = 0.025), and lower ejection fraction (P = 0.02). Of the 107 patients with PMI, 20.6% died of cardiac cause during the same hospital stay. The following factors increased the odds ratios for cardiac death: age (P = 0.001), recent congestive heart failure (P = 0.01), type of surgery (P = 0.04), emergency surgery (P = 0.02), lower intraoperative diastolic blood pressure (P = 0.001), new intraoperative ST-T changes (P = 0.01), and increased intraoperative use of blood (P = 0.005). Patients who underwent coronary artery bypass grafting, even more than 12 months before index surgery, had a 79% reduction in risk of death if they had PMI (P = 0.01). Multivariable analysis revealed preoperative definitive diagnosis of coronary artery disease (P = 0.001) and significant valvular disease (P = 0.03) were associated with increased risk of PMI. Congestive heart failure less than 1 yr before index vascular surgery (P = 0. 0002) and increased intraoperative use of blood (P = 0.007) were associated with cardiac death. The history of coronary artery bypass grafting reduced the risk of cardiac death (P = 0.04) in patients with PMI. CONCLUSIONS: The in-hospital cardiac mortality rate is high for patients who undergo vascular surgery and experience clinically significant PMI. Stress of surgery (increased intraoperative bleeding and aortic, peripheral vascular, and emergency surgery), poor preoperative cardiac functional status (congestive heart failure, lower ejection fraction, diagnosis of coronary artery disease), and preoperative history of coronary artery bypass grafting are the factors that determine perioperative cardiac morbidity and mortality rates.

Usefulness of CD79b expression in the diagnosis of B-cell chronic lymphoproliferative disorders.

We evaluated anti-CD79b for its usefulness in the diagnosis of B-cell chronic lymphoproliferative disorders (BCLPDs), particularly chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). We analyzed 100 BCLPDs for CD5, CD19, CD20, CD23, CD79b, and surface immunoglobulin light chain (sIg) expression by 4-color flow cytometry. CD20, CD79b, and sIg expression were quantified. Correlational analysis and univariable and multivariable logistic regression models were used to determine the best combination of antigens for the immunophenotypic classification of CLL vs other BCLPDs. Positive and statistically significant Spearman pairwise correlations between CD20, CD79b, and sIg fluorescence intensity were demonstrated. In the simplest models in which a single variable was considered, cutoff points were chosen that gave misclassification rates for CLL of 16% for CD79b, 19% for sIg, and 18% for CD20. Low-intensity CD79b, CD20, and sIg are associated highly with CLL. A panel containing CD5, CD19, CD23, and sIg allowed correct classification of most cases. Addition of CD20 or CD79b improved diagnostic accuracy; CD79b was slightly better than CD20. CD79b seems to be a useful addition to a standard flow cytometry panel for the evaluation of BCLPDs.

Hepatocyte transplantation in rats with decompensated cirrhosis.

Hepatocyte transplantation improves the survival of laboratory animals with experimentally induced acute liver failure and the physiological abnormalities associated with liver-based metabolic deficiencies. The role of hepatocyte transplantation in treating decompensated liver cirrhosis, however, has not been studied in depth. To address this issue, cirrhosis was induced using phenobarbital and carbon tetrachloride (CCL(4)) and animals were studied only when evidence of liver failure did not improve when CCL(4) was held for 4 weeks. Animals received intrasplenic transplantation of syngeneic rat hepatocytes (G1); intraperitoneal transplantation of syngeneic rat hepatocytes (G2); intraperitoneal transplantation of a cellular homogenate of syngeneic rat hepatocytes (G3); intraperitoneal transplantation of syngeneic rat bone marrow cells (G4); or intrasplenic injection of Dulbecco's modified Eagle medium (DMEM) (G5). After transplantation, body weight and serum albumin levels deteriorated over time in all control (G2-G5) animals but did not deteriorate in animals receiving intrasplenic hepatocyte transplantation (G1) (P <.01). Prothrombin time (PT), total bilirubin, serum ammonia, and hepatic encephalopathy score were also significantly improved toward normal in animals receiving intrasplenic hepatocyte transplantation (P <. 01). More importantly, survival was prolonged after a single infusion of hepatocytes and a second infusion prolonged survival from 15 to 128 days (P <.01). Thus, hepatocyte transplantation can improve liver function and prolong the survival of rats with irreversible, decompensated cirrhosis and may be useful in the treatment of cirrhosis in humans.

Nitric oxide regulation of asthmatic airway inflammation with segmental allergen challenge.

BACKGROUND: Despite evidence of increased nitric oxide (NO) in asthmatic compared with healthy individuals, the role of NO in airway inflammation is unclear. OBJECTIVE: The purpose of the study was to determine the in vivo effects of localized allergen challenge on airway NO levels and transcription factor activation. METHODS: In this study localized allergen challenge was used as a model of asthmatic exacerbation to determine the relationship of NO to airway inflammation. RESULTS: With allergen challenge, asthmatic patients had a rise in airway NO levels, whereas NO levels in healthy controls did not change. The increased NO in asthma with allergen challenge compared with healthy control subjects was associated with an increase in inflammatory cytokines (GM-CSF and macrophage inflammatory protein-1) in epithelial lining fluid and eosinophilic infiltrate in bronchoalveolar lavage fluid (BAL) and biopsy specimens. To investigate the mechanisms of cytokine gene expression, activation of the transcription factors activator protein-1 and nuclear factor-kappaB (NF-kappaB) in cells from BAL were evaluated. Activator protein-1 was not activated before or after local allergen challenge. In contrast, NF-kappaB activation was less in BAL cells from asthmatic patients with increased NO in comparison with controls. CONCLUSION: Our studies are the first to suggest an inverse correlation between NF-kappaB and airway NO in a localized segmental allergen challenge model in allergic asthmatic patients. The current study demonstrates that activation of the inflammatory response (eg, cytokines, cellular infiltrate) in allergic asthmatic patients is temporally associated with increased airway NO. We propose that NO that is up-regulated by cytokines is part of an autoregulatory feedback loop (ie, allergen challenge stimulates inflammatory cytokine production, which in turn stimulates NO production, and NO down-regulates cytokine production).