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Biomedical subjects

Ulrich Guller

Publications and source records attributed to Ulrich Guller.

At least 19 recordsLinked to original sources

Trends in the epidemiology of total shoulder arthroplasty in the United States from 1990-2000.

OBJECTIVE: Longitudinal trends in epidemiology and utilization of total shoulder arthroplasty (TSA) have not been previously reported. We evaluated trends in the distribution of age, race, hospital volume and teaching status, outcomes, and indications for TSA during the last decade. METHODS: TSA cases (n = 12,758) were extracted from the 1990-2000 Nationwide Inpatient Sample databases. TSA trends were obtained for 3 time periods: 1990-1993 (period I), 1994-1997 (period II), and 1998-2000 (period III). RESULTS: Between 1990 and 2000, there were minor increases in the rate of TSA in most age groups. Ninety-three percent of the patients undergoing TSA in all 3 time periods were white. An increased proportion of patients were operated on in high volume hospitals in period III as compared with period I. Patients discharged to inpatient rehabilitation facilities after surgery had longer lengths of in-hospital stays as compared with those discharged home. Osteoarthritis was diagnosed in an increasing proportion of patients undergoing TSA (56.6% in period I versus 70.9% in period III). CONCLUSION: There was a minor increase in the rate of TSA, and almost no change in use of TSA by nonwhites from 1990 through 2000. Efforts to understand and narrow this apparent underutilization of TSA among nonwhites are required. Further research should determine whether the observed shift of TSA to high volume centers improves surgical outcomes.

Adult↗

Surgical outcomes research based on administrative data: inferior or complementary to prospective randomized clinical trials?

The importance of surgical research has gained new prominence over the past decades as the relevance of well designed and well conducted studies has become increasingly evident. There are two basic but diametrically different methods of conducting research: the prospective randomized clinical trial and the retrospective surgical outcomes study based on administrative data. Administrative databases contain data that were initially collected for purposes other than scientific research. Whereas the prospective randomized clinical trial is familiar to most surgeons, surgical outcomes research based on administrative data constitutes a genre of investigation that is often unfamiliar to and even disparaged by the surgical community. In the present article, the strengths and weaknesses of both prospective randomized clinical trials and retrospective surgical outcomes research are discussed. Specifically, the advantages and limitations of investigations based on large administrative databases are outlined. Because both study designs play an important role in surgical research, carefully designed and implemented surgical outcomes research based on administrative data should be viewed as being complementary and not inferior to prospective randomized clinical trials.

Biomedical Research↗

Carbon dye staining of sentinel lymph nodes facilitates microstaging of colon cancer patients.

BACKGROUND: Carbon dye, when peritumourally injected, permanently marks the drainage site of sentinel lymph nodes (SLN). The objective of the current study was to evaluate whether the use of carbon dye facilitated the detection of small nodal tumour infiltrates in colon cancer patients. METHODS: In a prospective trial, 19 patients underwent open, oncological resections of localized colon cancer and SLN procedure according to a standardized protocol. Isosulfan blue 1% and sterile filtered carbon dye (mixed 1:1) were injected into the subserosa circumferentially around the tumour. Lymph nodes staining blue were marked as SLN. Serial sections of each SLN were stained with hematoxylin and eosin (H&E) and with the pancytokeratin marker AE1/AE3. The intranodal presence and site of carbon particles were noted and compared with the location of possible tumour infiltrates. RESULTS: Identification of at least one SLN was successful in 18 patients (identification rate 95%). Four patients (22%) were pN+, 11 (61%) were pN0(i-). Three patients (17%) were upstaged from pN0(i-) to pN0(i+) as isolated tumour cells were detected in their SLN: in two (11%) of the three patients, carbon dye and isolated tumour cells were found in the same nodal compartment, hence facilitating the recognition of isolated tumour cells by the pathologist. CONCLUSION: The use of carbon dye in the SLN procedure for colon cancer may facilitate the detection of small nodal tumour infiltrates.

Aged↗

Detecting pheochromocytoma: defining the most sensitive test.

OBJECTIVE: To define the most sensitive biochemical test to establish the diagnosis of pheochromocytoma and also to assess the potential role of iodine 131-labeled metaiodobenzylguanidine scintigraphy (I-MIBG) in the diagnosis of this tumor. SUMMARY BACKGROUND DATA: Pheochromocytoma is a rare, catecholamine-producing tumor with preferential localization in the adrenal gland. Despite its importance, the most sensitive test to establish the diagnosis remains to be defined. METHODS: Prospective data collection was done on patients with pheochromocytoma treated at the Duke University Medical Center and the Durham Veterans Affairs Medical Center, Durham, NC. All urinary, plasma, and platelet analyses were highly standardized and supervised by one investigator (J.M.F.). I-MIBG scans were independently reviewed by 2 nuclear medicine physicians. RESULTS: A total of 152 patients (55.3% female) were enrolled in the present analysis. Patients were predominantly white (73.7%). Spells (defined as profuse sweating, tachycardia, and headache) and hypertension at diagnosis were present in 51.4% and 66.6%, respectively. Bilateral disease was found in 12.5%, malignant pheochromocytoma in 29.6%, and hereditary forms in 23.0%. The most sensitive tests were total urinary normetanephrine (96.9%), platelet norepinephrine (93.8%), and I-MIBG scintigraphy (83.7%). In combination with I-MIBG scintigraphy, platelet norepinephrine had a sensitivity of 100%, plasma norepinephrine/MIBG of 97.1%, total urine normetanephrine/MIBG of 96.6%, and urine norepinephrine/MIBG of 95.3%. CONCLUSIONS: The tests of choice to establish the diagnosis of pheochromocytoma are urinary normetanephrine and platelet norepinephrine. A combination of I-MIBG scintigraphy and diagnostic tests in urine, blood, or platelets does further improve the sensitivity. We thus advocate performing an MIBG scan if the diagnosis of pheochromocytoma is clinically suspected and catecholamine measurements are within the normal range.

3-Iodobenzylguanidine↗

Clinical applications of virosomes in cancer immunotherapy.

Cancer immunotherapy is increasingly accepted as a treatment option for advanced stage disease. The identification of tumour-associated antigens in 1991 has prompted the development of antigen-specific immunotherapeutic strategies for a variety of cancers. Many of them result in some immunological responses in cancer patients; however, clinical results were not observed concomitantly with immunological responses; therefore, further improvements in the field of immunotherapy are urgently needed. Virosomes are lipidic envelopes devoid of genetic information, but which retain the antigenic profile and fusogenic properties from their viral origin. Virosomes are versatile antigen carriers and can be engineered to perform various tasks in cancer immunotherapy. Preclinical data have fostered the development of innovative clinical protocols. Hence, immunopotentiating reconstituted influenza virosomes will be assessed in breast and melanoma immunotherapy, and may contribute to the development of clinically effective cancer vaccines and ultimately improve patient outcomes. The objective of this review is to provide an overview of the potential clinical applications of virosomes as innovative and potentially effective reagents in active specific cancer immunotherapy.

Animals↗

NY-ESO-1/LAGE-1 coexpression with MAGE-A cancer/testis antigens: a tissue microarray study.

The characterization of the expression pattern of different families of cancer/testis (C/T) antigens in different tumors, at the protein level, might be of relevance in the development of multiantigen vaccine preparations for active specific immunotherapy. We have used tissue microarray (TMA) technology to explore in large numbers of tumor specimens the expression of NY-ESO-1/LAGE-1 C/T antigens and its correlation with MAGE-A expression by using D8.38 and 57B monoclonal antibodies (MAb). The epitopes recognized by these reagents in C/T antigens were identified by molecular mapping by using a bacterial expression system. Out of 2,052 samples, 119 (5.8%) scored positive upon staining with D8.38 NY-ESO-1/LAGE-1-specific MAb. Expression in >10% of cases was detectable in melanoma and basalioma (31.6 and 18.2%, respectively), large cell carcinomas and adenocarcinomas of the lung (17.8 and 10.5%, respectively), stomach adenocarcinomas of the intestinal type (13.2%), pT2-4 bladder TCC (18.2%), nonseminomatous carcinomas of the testis (10.4%) and liposarcomas (15.4%). Simultaneous expression of NY-ESO-1/LAGE-1 and MAGE-A C/T antigens was then addressed in a TMA where 101/845 and 73/845 samples (12 and 8.6%, respectively) showed evidence of MAGE-A or NY-ESO-1/LAGE-1 specific staining, respectively. In 35/845 specimens (4.1%) concomitant expression of MAGE-A and NY-ESO-1/LAGE-1 was observed (p = 0.0002). Discrepancies in the expression of NY-ESO-1/LAGE-1 and MAGE-A were conspicuously detectable in squamous cell carcinomas of the skin (MAGE-A positive but NY-ESO-1/LAGE-1 negative) and in liposarcomas (NY-ESO-1/LAGE-1 positive, but MAGE-A negative). Taken together, these data suggest novel areas of application of C/T antigens targeted active specific immunotherapy possibly based on multiantigen vaccine preparations.

Amino Acid Sequence↗

Relation between blood lead levels and childhood anemia in India.

Lead pollution is a substantial problem in developing countries such as India. The US Centers for Disease Control and Prevention has defined an elevated blood lead level in children as > or = 10 microg/dl, on the basis of neurologic toxicity. The US Environmental Protection Agency suggests a threshold lead level of 20-40 microg/dl for risk of childhood anemia, but there is little information relating lead levels <40 microg/dl to anemia. Therefore, the authors examined the association between lead levels as low as 10 mug/dl and anemia in Indian children under 3 years of age. Anemia was divided into categories of mild (hemoglobin level 10-10.9 g/dl), moderate (hemoglobin level 8-9.9 g/dl), and severe (hemoglobin level <8 g/dl). Lead levels <10 mug/dl were detected in 568 children (53%), whereas 413 (38%) had lead levels > or = 10-19.9 microg/dl and 97 (9%) had levels > or = 20 microg/dl. After adjustment for child's age, duration of breastfeeding, standard of living, parent's education, father's occupation, maternal anemia, and number of children in the immediate family, children with lead levels > or = 10 microg/dl were 1.3 (95% confidence interval: 1.0, 1.7) times as likely to have moderate anemia as children with lead levels <10 microg/dl. Similarly, the odds ratio for severe anemia was 1.7 (95% confidence interval: 1.1, 2.6). Health agencies in India should note the association of elevated blood lead levels with anemia and make further efforts to curb lead pollution and childhood anemia.

Age Distribution↗

Trends in epidemiology of knee arthroplasty in the United States, 1990-2000.

OBJECTIVE: There is little information on longitudinal trends in the epidemiology of total knee arthroplasty (TKA). This study was undertaken to determine whether, during the past decade, TKA rates increased in younger adults and older adults, whether utilization of TKA increased among minorities, and whether more patients underwent surgery at high-volume hospitals. METHODS: TKA cases (n = 443,008) were extracted from the 1990-2000 Nationwide Inpatient Sample database. TKA trends for 3 time periods were obtained (1990-1993 [period I], 1994-1997 [period II], and 1998-2000 [period III]). RESULTS: Between period I and period III, the proportion of TKAs performed increased by 95.2% in the 40-49-year age group and by 53.7% in the 50-59-year age group. Black patients and Hispanic patients were more likely to undergo TKA in period III than in period I (odds ratio [OR] = 1.6, 95% confidence interval [95% CI] 1.5-1.6 and OR 2.7, 95% CI 2.5-2.9, respectively). However, white patients accounted for 93.0%, 89.9%, and 87.5% of TKAs in the 3 time periods, respectively. In period III, the proportion of patients undergoing surgery in high-volume hospitals increased compared with periods I and II. Both mortality and length of hospital stay diminished significantly in period III, but the rate of discharge to an inpatient facility increased by 89.7% (period I to period III). CONCLUSION: Over the past decade, TKA was increasingly performed in younger patients, which suggests a broadening of indications for this procedure. Although utilization of TKA increased among minorities, the vast majority of TKAs were performed in white patients. Further efforts to narrow this disparity are required. The shift toward TKAs being increasingly performed at high-volume centers may improve surgical outcomes. Finally, the effect of increased discharge to inpatient facilities on TKA outcomes needs to be ascertained.

Adult↗

High hospital volume is associated with better outcomes for breast cancer surgery: analysis of 233,247 patients.

BACKGROUND: The relationship between hospital volume and outcomes needs to be further elucidated for low-risk procedures such as surgical therapy of localized breast cancer. The objective of this investigation was to assess the relationship between hospital volume and outcomes for breast cancer surgery. METHODS: A total of 233,247 patients who underwent breast-conserving therapy (BCT) and breast-ablative therapy (BAT) for localized breast cancer were extracted from 13 years (1988-2000) of the Nationwide Inpatient Samples. Hospital volume was classified as low (<30 cases/year), intermediate (> or =30 to <70 cases/year), and high (> or =70 cases/year). Multiple linear and logistic regression analyses were used to assess the risk-adjusted association between hospital volume and outcomes. RESULTS: In risk-adjusted analyses, patients operated on at low-volume hospitals were 3.04 (p = 0.03) times more likely to die after BCT compared with patients operated on at high-volume hospitals. Similarly, low-volume hospitals had a significantly higher likelihood of postoperative complications (odds ratio [OR] = 1.73, p = 0.01 for BCT; OR = 1.44, p < 0.001 for BAT) compared with high-volume hospitals. Compared with low-volume hospitals, length of hospital stay was significantly shorter and nonroutine patient discharge significantly lower for high-volume providers for both BCT and BAT (all p < 0.001). Patients were also significantly less likely to undergo BCT if operated on in a low- or intermediate-volume hospital compared with a high-volume provider (p < 0.001). CONCLUSIONS: High-volume hospitals had significantly lower nonroutine patient discharge, postoperative morbidity and mortality, shorter length of hospital stay, and higher likelihood of performing BCT. Referral of patients with localized breast cancer to high-volume hospitals may be justified.

Aged↗

Sample size matters: a guide for surgeons.

Considerations of sample size computations in the medical literature have gained increasing importance over the past decade and are now often mandatory for scientific grant proposals, protocols, and publications. However, many surgeons are ill-prepared to understand the parameters on which the appropriate sample size is based. The present article has several objectives: first, to review the need for sample size considerations; second, to explain the ingredients necessary for sample size computations in simple, nonmathematic language; third, to provide options for reducing the sample size if it seems impracticably large; and fourth, to help avoid some of the more common mistakes encountered when computing sample sizes.

Evidence-Based Medicine↗

Relationship between surgeon caseload and sphincter preservation in patients with rectal cancer.

PURPOSE: The aim of this study was to determine by means of a national database whether higher surgeon caseload correlates with greater utilization of sphincter-sparing procedures than of abdominoperineal resections in treatment of patients with rectal cancer. METHODS: Patients with a primary International Classification of Diseases-9 diagnosis code of rectal cancer who underwent a sphincter-sparing procedure or abdominoperineal resection were selected from the 1997 Nationwide Inpatient Sample, a database that represents 20 percent of all U.S. community hospital discharges. Multivariable logistic regression models were used on a 20 percent sample of this database to estimate the risk-adjusted relationship between surgeon caseload volume and the odds of receiving a sphincter-sparing procedure. All models were adjusted for age, gender, race, hospital region, and patient comorbidity. RESULTS: The study population (n = 477) was 70.4 percent white and 57.9 percent male with an average age of 67.6 years. The mean Deyo comorbidity score was 7.0. Patients treated by surgeons in the highest-volume category (> or =10 rectal cancer surgeries per year) compared with those treated by surgeons in the lowest-volume category (1-3 rectal cancer surgeries per year) were significantly more likely to undergo a sphincter-sparing procedure, after adjustment for other covariates (odds ratio = 5.05; 95 percent confidence interval, 2.5-10.22). CONCLUSION: This analysis suggests that rectal cancer patients treated by high-volume surgeons are five times more likely to undergo sphincter-sparing procedures than those treated by low-volume surgeon. This has significant implications for those seeking a sphincter-preserving option for the treatment of their rectal cancer.

Clinical Competence↗

Pre-, peri-, and posttreatment imaging of liver lesions.

This article provides an overview of current treatment approaches in patients with primary or secondary liver diseases. Emphasis is placed on MR imaging prior, during, and after various treatments, including liver resection, systemic chemotherapy, transcatheter arterial chemoembolization, ablative therapies, and liver transplantation. Findings described for MR imaging are directly applicable to findings for CT and potentially contrast-enhanced ultrasound. The authors' description, however, will deal mainly with MR imaging as this is the their preferred approach due to diagnostic accuracy and patient safety, and the findings are most demonstrative on MR imaging.

Diagnostic Imaging↗

Cryotherapy after ACL reconstruction: a meta-analysis.

Cryotherapy is a common treatment modality after orthopedic surgery procedures. Single institutional randomized clinical trials have evaluated the efficacy of cryotherapy after arthroscopically-assisted anterior cruciate ligament (ACL) reconstruction. Most of these studies were, however, underpowered to detect clinically relevant outcomes differences. This meta-analysis assessed the combined scientific evidence of studies evaluating the effectiveness of cryotherapy after arthroscopically-assisted ACL reconstruction. Electronic databases and bibliographic references of relevant articles were used to identify all relevant randomized clinical trials comparing cryotherapy to a placebo group after ACL reconstruction. Outcomes under investigation were postoperative drainage, range of motion, and pain. Random-effects models were used to combine the findings of the randomized controlled trials. Seven randomized clinical trials were included in the meta-analysis. Postoperative drainage (P=.23) and range of motion (P=.25) were not significantly different between cryotherapy and control group. However, cryotherapy was associated with significantly lower postoperative pain (P=.02). This meta-analysis showed that cryotherapy has a statistically significant benefit in postoperative pain control, while no improvement in postoperative range of motion or drainage was found. As the cryotherapy apparatus is fairly inexpensive, easy to use, has a high level of patient satisfaction, and is rarely associated with adverse events, we believe that cryotherapy is justified in the postoperative management of knee surgery.

Anterior Cruciate Ligament↗

Influence of obesity on surgical regional anesthesia in the ambulatory setting: an analysis of 9,038 blocks.

BACKGROUND: Regional anesthesia is increasing in popularity for ambulatory surgical procedures. Concomitantly, the prevalence of obesity in the United States population is increasing. The objective of the present investigation was to assess the impact of body mass index (BMI) on patient outcomes after ambulatory regional anesthesia. METHODS: This study was based on prospectively collected data including 9,038 blocks performed on 6,920 patients in a single ambulatory surgery center. Patients were categorized into three groups according to their BMI (<25 kg/m2, 25-29 kg/m2, > or =30 kg/m2). Block efficacy, rate of acute complications, postoperative pain (at rest and with movement), postoperative nausea and vomiting, rate of unscheduled hospital admissions, and overall patient satisfaction were assessed. Linear and logistic multivariable analyses were used to obtain the risk-adjusted effect of BMI on these outcomes. RESULTS: Of all patients 34.8% had a BMI <25 kg/m2, 34.0% were overweight (BMI 25-29 kg/m2), and 31.3% were obese (BMI > or = 30 kg/m2). Patients with BMI > or =30 kg/m2 were 1.62 times more likely to have a failed block (P = 0.04). The unadjusted rate of acute complications was higher in obese patients (P = 0.001). However, when compared with patients with a normal BMI, postoperative pain at rest, unanticipated admissions, and overall satisfaction were similar in overweight and obese patients. CONCLUSIONS: The present investigation shows that obesity is associated with higher block failure and complication rates in surgical regional anesthesia in the ambulatory setting. Nonetheless, the rate of successful blocks and overall satisfaction remained high in patients with increased BMI. Therefore, overweight and obese patients should not be excluded from regional anesthesia procedures in the ambulatory setting.

Adult↗

Comorbidities increase complication rates in patients having arthroplasty.

UNLABELLED: The objective of our study was to assess the effect of comorbidities (hypertension, diabetes, obesity, and their combinations) on postoperative complications and discharge status in patients having shoulder, hip, and knee arthroplasty (n = 959,839). The association between outcomes and each of the comorbidities was assessed using multivariable logistic regression after adjusting for age, race, household income, gender, and hospital volume. In the multivariable models, postoperative complications were more likely in patients with hypertension, diabetes, or obesity as compared with patients without these comorbidities (for hypertension, odds ratio = 1.07; 95% confidence interval range, 1.04-1.11; for obesity, odds ratio = 1.3; 95% confidence interval range, 1.22-1.41). The likelihood of a nonhomebound disposition of patients on discharge was 1.30 times (95% confidence interval range, 1.27-1.32) in patients with diabetes and 1.45 times (95% confidence interval range, 1.40-1.49) in patients who were obese as compared with patients without these respective comorbidities. Patients with a combination of comorbidities also had a higher likelihood of postoperative complications and nonhomebound discharge. Results of our study showed that hypertension, diabetes, and obesity are independent predictors of increased postoperative complications and non-homebound discharge in patients undergoing shoulder, hip, or knee arthroplasty. LEVEL OF EVIDENCE: Prognostic study, Level II-1 (retrospective study). See the Guidelines for Authors for a complete description of levels of evidence.

Aged↗

Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analysis of 150 patients after SLN biopsy.

OBJECTIVE: To assess the axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases (>0.2 mm to 0.2 mm to <or=2 mm) in 12% (27/224) of patients. Adjuvant therapy did not differ between the group of SLN-negative patients and those with SLN micrometastases. After a median follow-up of 42 months (range 12-64 months), 99% (222/224) of evaluable patients were reassessed. While 1 patient with a negative SLN developed axillary recurrence (0.7%, 1/122), all 27 patients with SLN micrometastases were disease-free at the last follow-up control. CONCLUSIONS: Axillary recurrences in patients with negative SLN or SLN micrometastases did not occur more frequently after SLN biopsy alone compared with results from the recent literature regarding breast cancer patients undergoing formal ALND. Based on a median follow-up of 42 months-one of the longest so far in the literature-the present investigation does not provide evidence that the presence of SLN micrometastases leads to axillary recurrence or distant disease and supports the theory that formal ALND may be omitted in these patients.

Adult↗

A suite of web applications to streamline the interdisciplinary collaboration in secondary data analyses.

BACKGROUND: We describe a system of web applications designed to streamline the interdisciplinary collaboration in outcomes research. DESCRIPTION: The outcomes research process can be described as a set of three interrelated phases: design and selection of data sources, analysis, and output. Each of these phases has inherent challenges that can be addressed by a group of five web applications developed by our group. QuestForm allows for the formulation of relevant and well-structured outcomes research questions; Research Manager facilitates the project management and electronic file exchange among researchers; Analysis Charts facilitate the communication of complex statistical techniques to clinicians with varying previous levels of statistical knowledge; Literature Matrices improve the efficiency of literature reviews. An outcomes research question is used to illustrate the use of the system. CONCLUSIONS: The system presents an alternative to streamline the interdisciplinary collaboration of clinicians, statisticians, programmers, and graduate students.

Cooperative Behavior↗