Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in Caenorhabditis elegans.

In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found in the nematode Caenorhabditis elegans: after the single off-center crossover divides the chromosome into two segments, or arms, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the shorter or longer arm, where they promote the correct timing of cohesion loss through as-yet unknown mechanisms. Here, we investigate the meiotic axis HORMA-domain protein HIM-3 and show that it becomes phosphorylated at its C-terminus, within the conserved "closure motif" region bound by the related HORMA-domain proteins HTP-1 and HTP-2. Binding of HTP-2 is abrogated by phosphorylation of the closure motif in in vitro assays, strongly suggesting that in vivo phosphorylation of HIM-3 likely modulates the hierarchical structure of the chromosome axis. Phosphorylation of HIM-3 only occurs on synapsed chromosomes, and similarly to other previously-described phosphorylated proteins of the synaptonemal complex, becomes restricted to the short arm after designation of crossover sites. Regulation of HIM-3 phosphorylation status is required for timely disassembly of synaptonemal complex central elements from the long arm, and is also required for proper timing of HTP-1 and HTP-2 dissociation from the short arm. Phosphorylation of HIM-3 thus plays a role in establishing the identity of short and long arms, thereby contributing to the robustness of the two-step chromosome segregation.

The role of foreign body response in peri-implantitis: What is the evidence?

Historically, there has been broad consensus that osseointegration represents a homeostasis between a titanium dental implant and the surrounding bone, and that the crestal bone loss characteristic of peri-implantitis is a plaque-induced inflammatory process. However, this notion has been challenged over the past decade by proponents of a theory that considers osseointegration an inflammatory process characterized by a foreign body reaction and peri-implant bone loss as an exacerbation of this inflammatory response. A key difference in these two schools of thought is the perception of the relative importance of dental plaque in the pathogenesis of crestal bone loss around implants, with obvious implications for treatment. This review investigates the evidence for a persistent foreign body reaction at osseointegrated dental implants and its possible role in crestal bone loss characteristic of peri-implantitis. Further, the role of implant-related material release within the surrounding tissue, particularly titanium particles and corrosion by-products, in the establishment and progression in peri-implantitis is explored. While it is acknowledged that these issues require further investigation, the available evidence suggests that osseointegration is a state of homeostasis between the titanium implant and surrounding tissues, with little evidence that a persistent foreign body reaction is responsible for peri-implant bone loss after osseointegration is established. Further, there is a lack of evidence for a unidirectional causative role of corrosion by-products and titanium particles as possible non-plaque related factors in the etiology of peri-implantitis.

The emerging role of small extracellular vesicles in saliva and gingival crevicular fluid as diagnostics for periodontitis.

Periodontitis is a highly prevalent multifactorial chronic inflammatory disease associated with a destructive host immune-inflammatory response to microbial dysbiosis. Current clinical diagnosis is reliant on measuring past periodontal tissue loss, with a lack of molecular biomarkers to accurately diagnose periodontitis activity in 'real-time'. Thus, discovery of new classes of diagnostic biomarkers is of critical importance in periodontology. Small extracellular vesicles (<200 nm in diameter; sEVs) from oral biofluids (saliva and gingival crevicular fluid-GCF) are lipid-encapsulated bilayered vesicles and have recently emerged as a potential source of biomarkers for periodontal disease (gingivitis and periodontitis), due to the cargo of protein, genetic material and lipids derived from their parent cells. There is limited information on the isolation and characterisation methods of saliva/GCF-sEVs or the characterisation of sEVs cargo as biomarkers for periodontitis. In this review, we detail the composition of sEVs and summarise their isolation and characterisation from saliva and GCF. The potential role of saliva and GCF-derived sEVs in periodontitis diagnosis is also explored. It is proposed that sEVs cargo, including protein, microRNA, message RNA and DNA methylation, are potential biomarkers for periodontitis with good diagnostic power (area under the curve-AUC > 0.9).

The meiotic phosphatase GSP-2/PP1 promotes germline immortality and small RNA-mediated genome silencing.

Germ cell immortality, or transgenerational maintenance of the germ line, could be promoted by mechanisms that could occur in either mitotic or meiotic germ cells. Here we report for the first time that the GSP-2 PP1/Glc7 phosphatase promotes germ cell immortality. Small RNA-induced genome silencing is known to promote germ cell immortality, and we identified a separation-of-function allele of C. elegans gsp-2 that is compromised for germ cell immortality and is also defective for small RNA-induced genome silencing and meiotic but not mitotic chromosome segregation. Previous work has shown that GSP-2 is recruited to meiotic chromosomes by LAB-1, which also promoted germ cell immortality. At the generation of sterility, gsp-2 and lab-1 mutant adults displayed germline degeneration, univalents, histone methylation and histone phosphorylation defects in oocytes, phenotypes that mirror those observed in sterile small RNA-mediated genome silencing mutants. Our data suggest that a meiosis-specific function of GSP-2 ties small RNA-mediated silencing of the epigenome to germ cell immortality. We also show that transgenerational epigenomic silencing at hemizygous genetic elements requires the GSP-2 phosphatase, suggesting a functional link to small RNAs. Given that LAB-1 localizes to the interface between homologous chromosomes during pachytene, we hypothesize that small localized discontinuities at this interface could promote genomic silencing in a manner that depends on small RNAs and the GSP-2 phosphatase.

Associations between inflammation-related LL-37 with subgingival microbial dysbiosis in rheumatoid arthritis patients.

OBJECTIVE: This study investigated the subgingival microbial profile of rheumatoid arthritis (RA) patients and its associations with disease parameters and the inflammation-related antimicrobial peptide, LL-37. METHODS: RA and non-RA (NRA) patients were assessed for periodontal status and divided into periodontitis (CP), gingivitis (G), and healthy (H) groups. Subgingival plaque 16s rRNA gene sequencing data was processed and analyzed using the CLC Genomic Workbench (Qiagen). Bacterial diversity and co-occurrence patterns were examined. Differential abundance between groups was also investigated. Associations between bacterial genera with disease parameters and LL-37 levels were explored qualitatively using canonical correlation analysis. RESULTS: Subgingival microbial community clustered in CP status. Co-occurrence network in NRA-H was dominated by health-associated genera, while the rest of the networks' key genera were both health- and disease-associated. RA-CP displayed highly inter-generic networks with a statistically significant increase in periodontal disease-associated genera (p<0.05). In NRA-H, disease parameters and LL-37 were correlated positively with disease-associated genera while negatively with health-associated genera. However, in the remaining groups, mixed positive and negative correlations were noted with genera. CONCLUSION: RA patients demonstrated subgingival microbial dysbiosis where the bacteria networks were dominated by health- and disease-associated genera. Mixed correlations with disease parameters and LL-37 levels were noted. CLINICAL RELEVANCE: The subgingival microbial dysbiosis in RA may predispose these patients to developing periodontal inflammation with an associated detrimental effect on host immune responses. Routine periodontal assessment may allow initiation of treatment strategies to minimize the effects of gingival inflammation on the existing heightened immune response present in RA patients.

Salivary Outer Membrane Vesicles and DNA Methylation of Small Extracellular Vesicles as Biomarkers for Periodontal Status: A Pilot Study.

Periodontitis is an inflammatory disease, associated with a microbial dysbiosis. Early detection using salivary small extracellular vesicles (sEVs) biomarkers may facilitate timely prevention. sEVs derived from different species (i.e., humans, bacteria) are expected to circulate in saliva. This pilot study recruited 22 participants (seven periodontal healthy, seven gingivitis and eight periodontitis) and salivary sEVs were isolated using the size-exclusion chromatography (SEC) method. The healthy, gingivitis and periodontitis groups were compared in terms of salivary sEVs in the CD9+ sEV subpopulation, Gram-negative bacteria-enriched lipopolysaccharide (LPS+) outer membrane vesicles (OMVs) and global DNA methylation pattern of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and N6-Methyladenosine (m6dA). It was found that LPS+ OMVs, global 5mC methylation and four periodontal pathogens (T. denticola, E. corrodens, P. gingivalis and F. nucleatum) that secreted OMVs were significantly increased in periodontitis sEVs compared to those from healthy groups. These differences were more pronounced in sEVs than the whole saliva and were more superior in distinguishing periodontitis than gingivitis, in comparison to healthy patients. Of note, global 5mC hypermethylation in salivary sEVs can distinguish periodontitis patients from both healthy controls and gingivitis patients with high sensitivity and specificity (AUC = 1). The research findings suggest that assessing global sEV methylation may be a useful biomarker for periodontitis.

Antibodies against citrullinated proteins in relation to periodontitis with or without rheumatoid arthritis: a cross-sectional study.

BACKGROUND: Previous studies have reported conflicting findings between serum anti-citrullinated protein antibodies (ACPA) levels in rheumatoid arthritis (RA) participants with and without periodontitis (Pd). This study aimed to analyse possible correlations between serum ACPA levels and clinical parameters in Pd and RA participants. METHODS: Full mouth periodontal examination (probing pocket depth, clinical attachment levels, gingival bleeding index, visual plaque index) was conducted and serum samples obtained from 80 participants comprising RA, Pd, both RA and Pd (RAPd) and healthy individuals (HC). Erythrocyte sedimentation rates (ESR) and periodontal inflamed surface area (PISA) were obtained. Serum samples were analysed for ACPA quantification using enzyme-linked immunosorbent assay (ELISA). RESULTS: Median levels (IU/mL) of ACPA (interquartile range, IQR) in RAPd, RA, Pd and HC groups were 118.58(274.51), 102.02(252.89), 78.48(132.6) and 51.67(91.31) respectively. ACPA levels were significantly higher in RAPd and RA as compared to HC group (p < 0.05). However, ACPA levels of any of the groups were not correlated with any clinical periodontal and RA parameters within the respective groups. CONCLUSIONS: At individual level, the amount of serum ACPA seem to have an increasing trend with the diseased condition in the order of RAPd > RA > Pd > HC. However, lack of any significant correlation between the serum ACPA levels with the clinical Pd and RA parameters warrants further studies to investigate the causal link between RA and Pd for such a trend. Further studies involving more inflammatory biomarkers might be useful to establish the causal link between Pd in the development and progression of RA or vice versa.

Periodontitis and rheumatoid arthritis: An update 2012-2017.

Rheumatoid arthritis and chronic periodontitis are both chronic inflammatory diseases characterized by an exacerbated inflammatory reaction that leads to destruction of bone and other connective tissue. Owing to these similarities, the relationship between these two diseases has been investigated for over two decades. In the 2013 proceedings from a workshop jointly held by the European Federation of Periodontology and American Academy of Periodontology in 2012 it was concluded that there was at least minimal evidence of an association between periodontitis and rheumatoid arthritis. In this review, we consider publications in the field over the past 5 years and determine whether the evidence for this relationship has increased.

Lung transplant in a recipient with tracheal bronchus.

We describe the intraoperative surgical management of tracheal bronchus encountered in a lung transplant recipient.

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status-A Pilot Study.

This pilot study aims to investigate whether salivary small extracellular vesicle (sEV)-associated microRNAs could act as potential biomarkers for periodontal disease status. Twenty-nine participants (10 who were healthy, nine with gingivitis, 10 with stage III/IV periodontitis) were recruited and unstimulated whole saliva samples were collected. Salivary sEVs were isolated using the size-exclusion chromatography (SEC) method and characterised by morphology, EV-protein and size distribution using transmission electron microscopy (TEM), Western Blot and Nanoparticle Tracking Analysis (NTA), respectively. Ten mature microRNAs (miRNAs) in salivary sEVs and saliva were evaluated using RT-qPCR. The discriminatory power of miRNAs as biomarkers in gingivitis and periodontitis versus healthy controls was evaluated by Receiver Operating Characteristics (ROC) curves. Salivary sEVs were comparable to sEVs morphology, mode, size distribution and particle concentration in healthy, gingivitis and periodontitis patients. Compared to miRNAs in whole saliva, three significantly increased miRNAs (hsa-miR-140-5p, hsa-miR-146a-5p and hsa-miR-628-5p) were only detected in sEVs in periodontitis when compared to that of healthy controls, with a good discriminatory power (area under the curve (AUC) = 0.96) for periodontitis diagnosis. Our study demonstrated that salivary sEVs are a non-invasive source of miRNAs for periodontitis diagnosis. Three miRNAs that are selectively enriched in sEVs, but not whole saliva, could be potential biomarkers for periodontal disease status.

Impact of periodontitis on quality of life among subjects with rheumatoid arthritis: a cross sectional study.

BACKGROUND: This study aimed to assess the impact of periodontitis (PD) on the health related quality of life (HRQoL) and oral health related QoL (OHRQoL) of subjects with rheumatoid arthritis (RA) and PD. METHODS: Subjects from dental and RA clinics were screened. Complete periodontal examinations were performed. Subjects were divided into 4 groups: RA-PD, RA, PD and healthy controls (HC). Questionnaires on characteristics and Malaysian versions of Oral Health Impact Profile (OHIP-14(M)) and Health Assessment Questionnaire (HAQ-DI)) were answered. RESULTS: A total of 187 subjects were included (29 RA-PD, 58 RA, 43 PD and 57 HC). OHIP-14(M) severity score was highest in the PD group (17.23 ± 10.36) but only significantly higher than the HC group (p < 0.05). The HAQ-DI scores of the RA group was significantly higher than the PD and HC groups (p < 0.05). The interaction between the effects of PD and RA on the OHRQoL and HRQoL was statistically significant (p < 0.05). CONCLUSION: PD and RA subjects both suffer impacts on their OHRQoL and HRQoL respectively. The interaction effect of both diseases significantly conferred impacts on their OHRQoL and HRQoL as measured by the OHIP-14(M) and HAQ-DI.

Soil-transmitted helminth infections.

More than a quarter of the world's population is at risk of infection with the soil-transmitted helminths Ascaris lumbricoides, hookworm (Ancylostoma duodenale and Necator americanus), Trichuris trichiura, and Strongyloides stercoralis. Infected children and adults present with a range of medical and surgical conditions, and clinicians should consider the possibility of infection in individuals living in, or returning from, endemic regions. Although safe and effective drugs are donated free to endemic countries, only half of at-risk children received treatment in 2016. This Seminar describes the epidemiology, lifecycles, pathophysiology, clinical diagnosis, management, and public health control of soil-transmitted helminths. Previous work has questioned the effect of population-level deworming; however, it remains beyond doubt that treatment reduces the severe consequences of soil-transmitted helminthiasis. We highlight the need for refined diagnostic tools and effective control options to scale up public health interventions and improve clinical detection and management of these infections.

An appraisal of the role of specific bacteria in the initial pathogenesis of periodontitis.

BACKGROUND: Historically, inflammatory periodontal diseases (gingivitis and periodontitis) have been recognized as being primarily of bacterial origin. Bacteria are necessary for disease development, but the presence of specific bacteria does not guarantee progression to periodontitis. Periodontitis is a multifactorial disease; specific bacteria are associated with disease, but may not be the target of treatment. Gingivitis and periodontitis are inflammatory conditions associated with bacterial overgrowth. AIM: To analyse evidence for established thought that specific bacteria directly participate in the pathogenesis of periodontitis and question the long-held tenet that penetration of the periodontal connective tissues by bacteria and their products is a significant phase in the initial development of periodontitis. METHODS: The literature was searched for studies on initiation of gingivitis and periodontitis by specific pathogens. The search results were insufficient for a systematic review and have been summarized in a commentary instead. RESULTS: There is very little evidence in the literature to support the commonly held concept that specific bacteria initiate periodontitis. CONCLUSION: We present evidence for a paradigm supporting the central role of inflammation, rather than specific microbiota, in the early pathogenesis of periodontitis, and discuss whether controlling the inflammation can influence the character and composition of the periodontal infection.

Aspiration for acute pilonidal abscess-a cohort study.

BACKGROUND: The traditional open incision and drainage of a pilonidal abscess is associated with slow healing and delayed return to normal daily activities. The aim of this study is to assess safety, effectiveness, and patient satisfaction of aspiration followed by antibiotics for a pilonidal abscess. MATERIAL AND METHODS: All patients presenting with an acute pilonidal abscess during the period December 2010 and December 2014 in York Hospital, UK, were treated with bedside aspiration under local anesthetic, followed by oral cefalexin and metronidazole for 7 days. Patients with immunosuppression, diabetes, overlying skin necrosis, and perforation were excluded. Complications of the procedure were prospectively recorded. Long-term outcomes and overall patients' satisfaction were assessed with the use of mailed questionnaires and Visual Analogue Scales (VAS) (0 = not satisfied at all, 10 = very satisfied). RESULTS: One hundred sixty-nine patients presented with an acute pilonidal abscess and a total of 100 patients were treated with aspiration and antibiotics. There were 50 women (50%) and the median (interquartile range [IQR]) age of the cohort was 24 (14) years. Eleven patients had a history of a previous pilonidal procedure. Seven patients were treated successfully with a reaspiration. Overall, 10 patients required incision and drainage after a median (IQR) follow-up time of 29 (47) months. Fifty-six patients returned completed questionnaires. The median (IQR) of the VAS for the overall satisfaction of the procedure was 9 (5). CONCLUSIONS: Aspiration of a pilonidal abscess in selected patients is effective in 83%, and it is associated with high overall satisfaction rates.

The evolving management of the appendix mass in the era of laparoscopy and interventional radiology.

AIM: An appendix mass is the result of a walled-off perforation of the appendix which localises, resulting in a mass and it is encountered in up to 7% of patients presenting with acute appendicitis. However, its management is controversial due to the lack of high level evidence. This review article sets out a rationale diagnostic and therapeutic strategy for the appendix mass based upon up-to-date available evidence. METHODS: A literature review of the investigation and management of appendix mass/complicated appendicitis was undertaken using PubMed, EMBASE and Google Scholar. RESULTS/CONCLUSION: No prospective studies were identified. The great majority of recent evidence supports a conservative management approach avoiding urgent appendicectomy because of the high risk of major complications and bowel resection. Appendix abscesses over 5 cm in diameter and persistent abscesses should be drained percutaneously along with antibiotics. Appendix phlegmon should be treated with antibiotics alone. Surgery is reserved for patients who fail conservative treatment. Routine interval appendicectomy is not recommended, but should be considered in the context of persistent faecolith, ongoing right iliac fossa pain, recurrent appendicitis and appendix mass persistent beyond 2 weeks. Clinicians should be particularly wary of patients with appendix mass aged over 40 and those with features suggesting malignancy.

Immunomodulatory Properties of Induced Pluripotent Stem Cell-Derived Mesenchymal Cells.

MSC-like populations derived from induced pluripotent stem cells (iPSC-MSC) serve as an alternative stem cell source due to their high proliferative capacity. In this study, we assessed the immunomodulatory potential of iPSC-MSC generated from periodontal ligament (PDL) and gingival (GF) tissue. The iPSC-MSC lines exhibited a similar level of suppression of mitogen-stimulated peripheral blood mononuclear cells (PBMNC) proliferation compared to their respective parental fibroblast populations in vitro. Moreover, iPSC-MSC demonstrated the ability to suppress T-cells effector cells, Th1/Th2/Th17 populations, and increase levels of Treg cells. In order to investigate the mechanisms involved, expression of common MSC-derived soluble factors known to supress lymphocyte proliferation were assessed in iPSC-MSC cultured with PBMNC with direct cell-cell contact or separated in transwells. Real-time PCR analysis of factors known to be involved in MSC mediated immune regulation, found a general trend of elevated IDO1 and IL6 transcript levels in iPSC-MSC lines and their respective primary cells co-cultured with activated PBMNC, with a wide range of gene expression levels between the different mesenchymal cell types. The results suggest that different iPSC-MSC may be useful as a potential alternative source of cells for future clinical use in therapeutic applications because of their potent immunosuppressive properties. J. Cell. Biochem. 117: 2844-2853, 2016. © 2016 Wiley Periodicals, Inc.

Gynecological manifestations, histopathological findings, and schistosoma-specific polymerase chain reaction results among women with Schistosoma haematobium infection: a cross-sectional study in Madagascar.

BACKGROUND: The pathophysiology of female genital schistosomiasis (FGS) is only partially understood. This study aims to describe the histopathological findings, polymerase chain reaction (PCR) results, and gynecological manifestations of FGS in women with different intensities of Schistosoma haematobium infection. METHODS: Women aged 15-35 years living in an S. haematobium-endemic area in Madagascar underwent pelvic and colposcopic examinations. Small biopsy specimens were obtained from lesions and examined histopathologically. Schistosoma PCR was done on urine, biopsy, cervicovaginal lavage, and genital mucosal surface specimens. RESULTS: Sandy patches and rubbery papules were found in 41 of 118 women (35%). Rubbery papules reflected an intense cellular immune reaction dominated by eosinophils, epithelial erosion, and viable ova. There was a significant decrease in the prevalence of rubbery papules with age, even after adjustment for urinary ova excretion. The sandy patches with grains showed moderate cellular immune reaction and ova (viable and/or calcified). They were most prevalent in cases with low-intensity urinary S. haematobium infection. Forty-two percent of women with Schistosoma-negative urine specimens had at least 1 genital specimen test positive for Schistosoma by PCR. CONCLUSIONS: The results indicate a diversity of lesions caused by S. haematobium and a dynamic evolution of the genital lesions. Schistosoma PCR may give an indication of the diagnosis.

Pathologic mucosal blood vessels in active female genital schistosomiasis: new aspects of a neglected tropical disease.

Female genital schistosomiasis is a frequent, but neglected cause of mucosal pathology in the female genital tract. Moreover, recent studies indicate that genital mucosal lesions may increase the risk of human immunodeficiency virus (HIV) infection. In rural Africa, detailed clinical images are rarely available alongside histologic sections, and further understanding of the pathogenesis of the genital mucosal lesions is needed. These cases represent previously unreported histopathologic photomicrographs and corresponding clinical images in 2 women with genital schistosomiasis. Dilated and tortuous mucosal venules seen in the cervicovaginal mucosa were found to contain viable Schistosoma haematobium eggs surrounded by a thrombus. The presence of abnormal mucosal blood vessels may be an indication of a persistent tissue reaction to S. haematobium ova in the lower female genital tract.

Periodontitis and periodontopathic bacteria as risk factors for rheumatoid arthritis: A review of the last 10 years.

Rheumatoid arthritis (RA) is characterized by chronic inflammatory destruction of joint tissue and is caused by an abnormal autoimmune response triggered by interactions between genetics, environmental factors, and epigenetic and posttranslational modifications. RA has been suggested to be interrelated with periodontitis, a serious form or stage of chronic inflammatory periodontal disease associated with periodontopathic bacterial infections, genetic predisposition, environmental factors, and epigenetic influences. Over the last decade, a number of animal and clinical studies have been conducted to assess whether or not periodontitis and associated periodontopathic bacteria constitute risk factors for RA. The present review introduces recent accumulating evidence to support the associations of periodontitis and periodontopathic bacteria with the risk of RA or the outcome of RA pharmacological treatment with disease-modifying antirheumatic drugs. In addition, the results from intervention studies have suggested an improvement in RA clinical parameters after nonsurgical periodontal treatment. Furthermore, the potential causal mechanisms underlying the link between periodontitis and periodontopathic bacteria and RA are summarized.

Should more patients continue aspirin therapy perioperatively?: clinical impact of aspirin withdrawal syndrome.

OBJECTIVE: To provide an evidence-based focused review of aspirin use in the perioperative period along with an in-depth discussion of the considerations and risks associated with its preoperative withdrawal. BACKGROUND: For patients with established cardiovascular disease, taking aspirin is considered a critical therapy. The cessation of aspirin can cause a platelet rebound phenomenon and prothrombotic state leading to major adverse cardiovascular events. Despite the risks of aspirin withdrawal, which are exacerbated during the perioperative period, standard practice has been to stop aspirin before elective surgery for fear of excessive bleeding. Mounting evidence suggests that this practice should be abandoned. METHODS: We performed a PubMed and Medline literature search using the keywords aspirin, withdrawal, and perioperative. We manually reviewed relevant citations for inclusion. RESULTS/CONCLUSIONS: Clinicians should employ a patient-specific strategy for perioperative aspirin management that weighs the risks of stopping aspirin with those associated with its continuation. Most patients, especially those taking aspirin for secondary cardiovascular prevention, should have their aspirin continued throughout the perioperative period. When aspirin is held preoperatively, the aspirin withdrawal syndrome may significantly increase the risk of a major thromboembolic complication. For many operative procedures, the risk of perioperative bleeding while continuing aspirin is minimal, as compared with the concomitant thromboembolic risks associated with aspirin withdrawal. Those cases where aspirin should be stopped include patients undergoing intracranial, middle ear, posterior eye, intramedullary spine, and possibly transurethral prostatectomy surgery.