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Background Postoperative respiratory failure is the most common serious postoperative pulmonary complication, yet little is known about factors that can reduce its incidence. We sought to elucidate modifiable factors associated with respiratory failure that developed within the first 5 d after an elective operation. Materials and Methods Matched case-control study of adults who had an operation at five academic medical centers between October 1, 2012 and September 30, 2015. Cases were identified using administrative data and confirmed via chart review by critical care clinicians. Controls were matched 1:1 to cases based on hospital, age, and surgical procedure. Results Our total sample (n = 638) was 56.4% female, 71.3% white, and had a median age of 62 y (interquartile range 51, 70). Factors associated with early postoperative respiratory failure included male gender (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.12-2.63), American Society of Anesthesiologists class III or greater (OR 2.85, 95% CI 1.74-4.66), greater number of preexisting comorbidities (OR 1.14, 95% CI 1.004-1.30), increased operative duration (OR 1.14, 95% CI 1.06-1.22), increased intraoperative positive end-expiratory pressure (OR 1.23, 95% CI 1.13-1.35) and tidal volume (OR 1.13, 95% CI 1.004-1.27), and greater net fluid balance at 24 h (OR 1.17, 95% CI 1.07-1.28). Conclusions We found greater intraoperative ventilator volume and pressure and 24-h fluid balance to be potentially modifiable factors associated with developing early postoperative respiratory failure. Further studies are warranted to independently verify these risk factors, explore their role in development of early postoperative respiratory failure, and potentially evaluate targeted interventions.

Background Administrative data can be used to identify cases of postoperative respiratory failure (PRF). We aimed to determine if recent changes to the Agency for Healthcare Research and Quality Patient Safety Indicator 11 (PSI 11) and adoption of clinical documentation improvement programs have improved the validity of PSI 11. We also analyzed reasons why PSI 11 was falsely triggered. Study design Cross-sectional study of all eligible discharges using health record data from five academic medical centers between October 1, 2012 and September 30, 2015. Results Of 437 flagged records, 434 (99.3%) were accurately coded and 414 (94.7%) represented true clinical PRF. None of the false positive records involved respiratory failure present on admission. Most (78.3%) false positive records required airway protection but did not have respiratory failure. Conclusion The validity of PSI 11 has improved with recent changes to the code criterion and adoption of clinical documentation improvement programs.

Background Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. Methods This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. Results Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81–10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04–1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06–1.22). Conclusions We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation.

Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF.This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF.Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81-10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04-1.44), and maximum intraoperative peak inspiratory pressure per cm HWe identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation.

BACKGROUND Current recommendations on carotid revascularization postulate that women have both increased perioperative risks, such as stroke and death, as well as reduced benefit from intervention. These recommendations do not include data on transcarotid artery revascularization (TCAR). This study strives to compare safety and benefits of TCAR, TFCAS (Transfemoral Carotid Artery Stenting), and CEA (Carotid Endarterectomy) with regard to patient sex. METHODS We performed retrospective analysis of the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) CEA and stenting registries, as well as TCAR Surveillance Project data. We compared outcomes after TCAR, TFCAS, and CEA based on sex. The primary outcome was the rate of in-hospital stroke or death. Secondary outcomes included in-hospital stroke, death, transient ischemic attack (TIA), myocardial infarction (MI), stroke/death/MI, stroke/TIA, and recurrent ipsilateral stroke and/or death at 1-year of follow-up. RESULTS A total of 75,538 patients were included, of which 28,960 (38.3%) were female and 46,578 (61.7%) were male. TFCAS females had more than 2 times higher odds of stroke/death (OR:2.85, 95%CI: 2.21-3.67, P < 0.001) and stroke/death/MI (OR:2.23, 95%CI:1.75-2.83, P < 0.001) when compared to CEA females. Odds of TIA were also higher in both TFCAS females (OR:2.01, 95%CI:1.19-3.42, P = 0.010) and TCAR females (OR:1.91, 95%CI:1.09-3.35, P = .023) when compared to CEA females. However, only TFCAS females experienced increased odds of stroke/TIA (OR:1.96, 95%CI:1.45-2.65, P < 0.001) when compared to CEA females. TFCAS males had almost twice the odds of stroke/death (OR:1.74, 95%CI:1.39-2.16, P < 0.001) and 44% higher odds of stroke/death/MI (OR:1.44, 95%CI:1.19-1.75, P < 0.001), and more than 3-times increased odds of death (OR:3.45, 95%CI:2.53-4.71, P < 0.001) when compared to CEA males. Odds of in-hospital stroke were comparable between TFCAS and CEA after adjusting for covariates. TCAR males have half the odds of MI when compared to CEA males (OR:0.52, 95%CI:0.34-0.80, P = 0.003). At 1-year TCAR had comparable risk of stroke/death while TFCAS had increased risk of stroke/death when compared to CEA among both males and females. CONCLUSION TCAR performed similarly to CEA in both sexes regardless of symptomatic status. Stroke/death and stroke/death/MI rates were similar in symptomatic and asymptomatic males and females treated by CEA or TCAR. The 1-year outcomes of TCAR were also comparable to CEA in both sexes. It seems that TCAR may be a safe alternative to CEA particularly in women when surgical risk prohibits CEA and while TFCAS is associated with substantial adverse outcomes.

Previous studies have shown no differences in the outcomes of transcarotid artery revascularization (TCAR) performed with general anesthesia (GA) vs local or regional anesthesia (LRA). To date, no study has specifically compared the outcomes of TCAR to those of carotid endarterectomy (CEA) stratified by anesthetic type. The aim of the present study was to identify the effect of the anesthetic type on the outcomes of TCAR vs CEA.Patients undergoing CEA and TCAR for carotid artery stenosis from 2016 to 2019 in the Vascular Quality Initiative were included. We excluded patients who had undergone concomitant procedures, patients with more than two stented lesions, and patients who had undergone the procedure for a nonatherosclerotic indication. Propensity score matching was performed between the two procedures stratified by the anesthetic type for age, sex, race, presenting symptoms, major comorbidities (ie, hypertension, diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease), previous coronary artery bypass grafting or percutaneous transluminal coronary intervention, previous CEA or carotid artery stenting, degree of ipsilateral stenosis, the presence of contralateral occlusion, and preoperative medications. Intergroup differences between the treatment groups and differences in the perioperative outcomes were tested using the McNemar test for categorical variables and the paired t test or Wilcoxon matched pairs signed rank test for continuous variables, as appropriate. The relative risk (RR) and 95% confidence intervals (CIs) were estimated as the ratio of the probability of the outcome event for the patients treated within each treatment group.A total of 65,337 patients were included. Of the 65,337 patients, 59,664 had undergone carotid revascularization under GA (91%). When performed with LRA, TCAR and CEA had similar rates of stroke, death, and MI. However, when performed with GA, patients undergoing TCAR had a 50% decreased risk of MI compared with those undergoing CEA under GA (0.5% vs 1.0%; RR, 0.50; 95% CI, 0.32-0.80; P .01). When stratified by symptomatic status, patients undergoing TCAR with GA for symptomatic carotid disease had a 67% decreased risk of MI compared with those undergoing CEA with GA for symptomatic disease (0.4% vs 1.2%; RR, 0.33; 95% CI, 0.15-0.75; P .01). In contrast, no difference was found in the risk of MI between patients undergoing CEA vs TCAR for asymptomatic carotid disease (0.6% vs 0.9%; RR, 0.64; 95% CI, 0.37-1.14; P = .13).The results from the present study have confirmed previous studies suggesting that TCAR confers a lower risk of MI compared with CEA. However, our findings demonstrated no differences in the MI rates between TCAR and CEA when performed with LRA. Patients undergoing TCAR under GA had lower rates of MI compared with patients undergoing CEA under GA. When stratified by symptomatic status, the benefit of TCAR persisted only for the symptomatic patients.

Background and Significance The increased emphasis on patient satisfaction has coincided with the growing adoption of electronic health records (EHRs) throughout the U.S. The 2001 Institute of Medicine Report, “Crossing the Quality Chasm,” identified patient-centered care as a key element of quality health care.[1] In response to this call, the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey was developed to assess patients' health care experiences in the inpatient setting. Simultaneously, financial incentives have facilitated the rapid adoption of EHR applications, with 84% of hospitals maintaining at least a basic EHR in 2015 (a ninefold increase since 2008).[2] Despite the concurrent deployment of patient satisfaction surveys and EHRs, there is a poor understanding of the relationship that may exist between physician usage of the EHR and patient satisfaction. Most prior research into the impact of the EHR on physician–patient communication has been observational, describing the behaviors of physicians and patients when the clinician accesses an EHR in the exam room. Past research has shown that encounters where physicians access the EHR are often filled with long pauses,[3] and that few clinicians attempt to engage patients by sharing what they are looking at on the screen.[4] A recent meta-analysis reviewing 53 papers found that only 7 studies attempted to correlate objective observations of physician communication behaviors with patient perceptions by eliciting feedback from the patients.[5] No study used a standardized assessment tool of patient satisfaction. The authors conclude that additional work is necessary to better understand the patient perspective of the presence of an EHR during a clinical encounter. Additionally, increasing EHR adoption and emphasis on patient satisfaction have also corresponded with rising physician burnout rates.[6] [7] Prior work suggests that EHR adoption may be contributing to this trend.[8] Burnout from the EHR may be due in part to the significant amount of time physicians spend logged into systems, documenting long after clinic has ended in effort to avoid disrupting the patient–physician relationship.[9] We used existing data sources to describe the relationship between the amount of time physicians spend logged in to the EHR—both during daytime hours as well after clinic hours—and performance on a validated patient satisfaction survey. Our null hypothesis is that there is no relationship between increased time logged in to the EHR and patient satisfaction.

Objectives Few studies have evaluated the association between anesthesia type and outcomes after endovascular angioplasty/stents for aortoiliac occlusive disease. The aim of the present study was to evaluate the association between primary anesthesia type and postprocedural complications for endovascular angioplasty of aortoiliac occlusion. Design Retrospective cohort study. Setting Multi-institutional. Participants The study comprised 3,110 patients undergoing endovascular angioplasty of aortoiliac occlusive disease, with 1,974 and 1,136 patients who underwent monitored anesthesia care (MAC) and general anesthesia (GA), respectively. The American College of Surgeons National Surgical Quality Improvement Program database for the years 2012 to 2016 was used for the present study. Interventions None. Measurements and Main Results The final analysis included 3,110 patients, 63% of whom received MAC and 37% of whom received GA. The mean age was 64 years among the GA group, of whom 57.2% were male. The mean age among that MAC group was 65 years, 55.8% of whom were male. After adjusting for demographic factors and preoperative comorbidities, there was a statistically significant lower odds of postoperative complications (ie, pulmonary complications, infection, intraoperative/postoperative transfusion, reoperation, and amputation) and shorter length of stay in the MAC group compared with the GA group (p Conclusions Although larger observational studies and randomized controlled trials are needed to further evaluate the potential effect of MAC versus GA, MAC anesthesia should be considered for patients undergoing endovascular angioplasty for aortoiliac occlusion.

Background Preoperative bevacizumab has been reported to increase postoperative complication risk following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We sought to review our experience with preoperative bevacizumab in patients undergoing CRS/HIPEC for peritoneal surface malignancy. Methods This is a retrospective review of patients who received neoadjuvant systemic therapy with or without bevacizumab prior to CRS/HIPEC at a high-volume academic center from 2007–2018. Results Of 499 patients, a total of 88 patients received neoadjuvant chemotherapy alone (n = 34) or in combination with bevacizumab (n = 54) within 3 months prior to CRS/HIPEC. No differences existed in 60-day major morbidity (17.6 vs. 16.7%, p = 0.81) or 60-day mortality (0 vs. 0%) between the two cohorts, and neoadjuvant bevacizumab was not associated with increased odds of overall complications (OR 0.86, 95% CI 0.35–2.09, p = 0.73) or major morbidity (OR 0.86, 95% CI 0.24–3.00, p = 0.81). Stratifying patients by primary tumor origin and post-operative complications did not reveal any significant differences between the two treatment groups. In addition, progression-free survival (PFS) and overall survival (OS) were similar in both cohorts. Conclusions Preoperative bevacizumab is not associated with increased morbidity or mortality following CRS/HIPEC. Neoadjuvant therapy employing this biologic agent is safe and should not be a deterrent for aggressive cytoreduction with curative intent.

Patients with peritoneal metastases from appendiceal cancer are at high risk of malignant bowel obstruction (MBO), which is associated with significant morbidity and mortality. There are no definitive treatment guidelines regarding operative intervention for MBO. We sought to evaluate the efficacy and safety of operative intervention in this population. We identified patients with peritoneal metastases from appendiceal cancer who underwent surgery for MBO at our institution between 2011 and 2018. Baseline characteristics, postoperative complications, and follow-up data were collected. The primary endpoint was obstruction-free survival (OFS). Other endpoints were postoperative recovery of bowel function, 60-day Clavien–Dindo (CD) morbidity, and overall survival (OS). Twenty-six patients underwent operative treatment for MBO, of whom 14 had high-grade (HG) histology and 12 had low-grade (LG) histology. Seven (25.9%) patients had severe (CD grade 3 or higher) 60-day complications, including one (3.8%) postoperative death. All remaining patients had return of bowel function and resumed oral intake during hospitalization. Six (23.1%) patients had repeat admissions for MBO after surgery. Median OFS was 17.0 months (95% confidence interval [CI] 2.3–31.8), and median OS was 18.5 months (95% CI 3.6–33.3) following surgery. In this carefully selected group of patients with peritoneal metastases from appendiceal cancer, surgery for MBO provided durable palliation with acceptable morbidity.

BackgroundA scholar'sh-index is defined as the number of h papers published, each of which has been cited at least h times. We hypothesized that the h-index strongly correlates with the academic rank of surgical oncologists.MethodsWe utilized the National Cancer Institute (NCI) website to identify NCI-designated Comprehensive Cancer Centers (CCC) and Doximity to identify the 50 highest-ranked general surgery residency programs with surgical oncology divisions. Demographic data of respective academic surgical oncologists were collected from departmental websites and Grantome. Bibliometric data were obtained from Web of Science.ResultsWe identified 544 surgical oncologists from 64 programs. Increased h-index was associated with academic rank (p

BackgroundThe increased uptake of contralateral prophylactic mastectomy (CPM) among breast cancer patients remains poorly understood. We hypothesized that the increased rate of CPM is represented in conversations on an online breast cancer community and may contribute to patients choosing this operation.MethodsWe downloaded 328,763 posts and their dates of creation from an online breast cancer community from August 1, 2000, to May 22, 2016. We then performed a keyword search to identify posts which mentioned breast cancer surgeries: contralateral prophylactic mastectomy (n=7095), mastectomy (n=10,889), and lumpectomy (n=9694). We graphed the percentage of CPM-related, lumpectomy-related, and mastectomy-related conversations over time. We also graphed the frequency of posts which mentioned multiple operations over time. Finally, we performed a qualitative study to identify factors influencing the observed trends.ResultsSurgically related posts (e.g., mentioning at least one operation) made up a small percentage (n=27,678; 8.4%) of all posts on this community. The percentage of surgically related posts mentioning CPM was found to increase over time, whereas the percentage of surgically related posts mentioning mastectomy decreased over time. Among posts that mentioned more than one operation, mastectomy and lumpectomy were the procedures most commonly mentioned together, followed by mastectomy and CPM. There was no change over time in the frequency of posts that mentioned more than one operation. Our qualitative review found that most posts mentioning a single operation were unrelated to surgical decision-making; rather the operation was mentioned only in the context of the patient's cancer history. Conversely, the most posts mentioning multiple operations centered around the patients' surgical decision-making process.ConclusionsCPM-related conversation is increasing on this online breast cancer community, whereas mastectomy-related conversation is decreasing. These results appear to be primarily informed by patients reporting the types of operations they have undergone, and thus appear to correspond to the known increased uptake of CPM.

Precision Medicine involves the delivery of a targeted, personalized treatment for a given patient. By harnessing the power of electronic health records (EHRs), we are increasingly able to practice precision medicine to improve patient outcomes. In this article, we introduce the scientific community at large to important building blocks for personalized treatment, such as terminology standards that are the foundation of the EHR and allow for exchange of health information across systems. We briefly review different types of clinical decision support (CDS) and present the current state of CDS, which is already improving the care patients receive with genetic profile-based tailored recommendations regarding diagnostic and treatment plans. We also report on limitations of current systems, which are slowly beginning to integrate new genomic data into patient records but still present many challenges. Finally, we discuss future directions and how the EHR can evolve to increase the capacity of the healthcare system in delivering Precision Medicine at the point of care. WIREs Syst Biol Med 2017, 9:e1378. doi: 10.1002/wsbm.1378 For further resources related to this article, please visit the WIREs website.

Background: Online health community (OHC) moderators help facilitate conversations and provide information to members. However, the necessity of the moderator in helping members achieve goals by providing the support they need remains unclear, with some prior research suggesting that moderation is unnecessary or even harmful for close-knit OHCs. Similarly, members’ perceptions of moderator roles are underexplored. Starting January of 2013, WebMD moderators stopped working for WebMD communities. This event provided an opportunity for us to study the perceived role of moderators in OHCs. Objective: We examine the OHC members’ perception on OHC moderators by studying their reactions toward the departure of moderators in their communities. We also analyzed the relative posting activity on OHCs before and after the departure of moderators from the communities among all members and those who discussed moderators’ departures. Methods: We applied a mixed-methods approach to study the posts of all 55 moderated WebMD communities by querying the terms relating to discussions surrounding moderators’ disappearance from the WebMD community. We performed open and axial coding and affinity diagramming to thematically analyze patients’ reactions to the disappeared moderators. The number of posts and poster groups (members and moderators) were analyzed over time to understand posting patterns around moderators’ departure. Results: Of 821 posts retrieved under 95 threads, a total of 166 open codes were generated. The codes were then grouped into 2 main themes with 6 total subthemes. First, patients attempted to understand why moderators had left and what could be done to fill the void left by the missing moderators. During these discussions, the posts revealed that patients believed that moderators played critical roles in the communities by making the communities vibrant and healthy, finding solutions, and giving medical information. Some patients felt personally attached with moderators, expressing they would cease their community participation. On the other hand, patients also indicated that moderators were not useful or sometimes even harmful for peer interactions. The overall communities’ posting activity, which was already in decline, showed no significant difference before and after the moderators’ departure. In fact, the overall posting activities of the communities were declining well before the moderators’ departure. These declining posting activities might be the reason why WebMD removed the moderators. Conclusion: Compassionate moderators who provide medical expertise, control destructive member posts, and help answer questions can provide important support for patient engagement in OHCs. Moderators are in general received positively by community members and do not appear to interfere with peer interactions. Members are well aware of the possibility of misinformation spreading in OHCs. Further investigation into the attitudes of less vocal community members should be conducted. [J Med Internet Res 2016;18(9):e247]

Completeness of cytoreduction is a significant predictor of long-term outcome after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Imaging has limited sensitivity to identify peritoneal metastases and therefore predict whether complete cytoreduction is possible. We reviewed our experience using laparoscopy to determine candidates for complete cytoreduction and HIPEC. This single-center, retrospective study examined patients from 2007 to 2014 who underwent laparoscopy to determine complete cytoreduction (CC-0/1)/HIPEC candidacy. Preoperative, intraoperative, and postoperative data were collected. A total of 145 laparoscopies were performed on 141 patients, 72 (51.1 %) of whom were female, with a median age of 53 years (range 20–79). The primary site was appendiceal in 67 (47.5 %) patients, colorectal in 43 (30.5 %), mesothelioma in 17 (12.1 %), unknown in 9 (6.4 %), small bowel in 3 (2.1 %), gastric in 1, and ovarian in 1 (0.7 % each). Overall, 115 (81.6 %) patients had prior abdominal surgery, 111 (76.6 %) had evidence of disease on imaging, and 117 (80.7 %) underwent prior chemotherapy, with a median of 5.9 weeks between the last treatment and laparoscopy (0.9–498.9 weeks). Four (2.8 %) intraoperative complications were observed (one liver laceration, two enterotomies, and one air embolus), and nine (6.2 %) postoperative complications [four (2.8 %) Clavien grade (CG) I, three (2.8 %) CG II, one (0.7 %) CG III (return to operating room) and one (0.7 %) CG IV (transient ischemic attack)]. Forty-eight patients deemed candidates by laparoscopy underwent CRS/HIPEC (positive predictive value 82.8 %). Diagnostic laparoscopy is a safe, feasible, and accurate staging tool in patients with suspected peritoneal metastases being considered for CRS.

Small ubiquitin-like modifier (SUMO) proteins are involved in a variety of cellular processes. Alterations in SUMO conjugation have been implicated in several human diseases, including cancer. Although the main cause of failure in cancer treatment is the development of drug resistance by cancer cells, the mechanisms of drug resistance are not fully understood. SUMO proteins are thought to play roles in various cellular pathways, but no studies have as yet compared the expression of the different SUMO proteins in chemosensitive and drug-resistant cancer cells. To determine the relationship between protein sumoylation and drug resistance, the expression of various SUMO isoforms has been studied and compared in the HL-60 cell line (a model for leukemic cells) and in HL-60RV cells (resistant to vincristine). Co-immunostaining of cells by anti-SUMO antibodies and antibodies against various nuclear subdomains has been examined by an advanced type of bioimaging analysis. Whereas SUMO-2/3 co-localizes exclusively with nuclear bodies containing promyelocytic leukemia protein in both cell types, SUMO-1 has also been seen in nucleolar regions of HL-60, but not in HL-60RV, cells. In HL-60 cells, SUMO-1 occurs adjacent to, but not co-localized with, the nucleolar marker fibrillarin. Western blot analysis has revealed higher levels of free SUMO and sumoylated products in drug-resistant cells and the presence of specific SUMO-1 conjugates in drug-sensitive HL-60 cells, possibly consistent with a specific nucleolar signal. Shortly after the induction of ethanol and oxidative stress, HL-60RV, but not HL-60, cells show increased accumulation of high-molecular-weight SUMO-2/3 conjugates. Thus, SUMO-1 probably has a specific role in the nucleoli of HL-60 cells, and the alteration of sumoylation might be a contributing factor in the development of drug resistance in leukemia cells.