Dysregulation of neutrophil extracellular traps (NETs)-related genes in the pathogenesis of diabetic kidney disease - Results from bioinformatics analysis and translational studies.

The role of Neutrophil extracellular traps (NETs) in the immunopathogenesis of Diabetic Kidney Disease (DKD) remains elusive. We used a machine learning approach to identify differentially expressed genes (DEGs) associated with NETs in human DKD kidney biopsy datasets and validated the results using single-nucleus RNA sequencing datasets. The expressions of these candidate genes and related cytokines were verified in blood obtained from DKD patients. Three NETs-associated genes (ITGAM, ITGB2 and TLR7) were identified, which all showed significant upregulation in both glomerular and tubulointerstitial compartments in human DKD kidneys. DKD patients showed significantly higher number of activated neutrophils with increased ITGAM and ITGB2 expression, higher serum IL-6 but lower IL-10, compared to healthy controls (p all <0.01). This study suggests that dysregulation of NETs-associated genes ITGAM and ITGB2 are related to the pathogenesis of DKD, and may serve as novel diagnostic markers and therapeutic targets in DKD.

Beyond black-box models: explainable AI for embryo ploidy prediction and patient-centric consultation.

PURPOSE: To determine if an explainable artificial intelligence (XAI) model enhances the accuracy and transparency of predicting embryo ploidy status based on embryonic characteristics and clinical data. METHODS: This retrospective study utilized a dataset of 1908 blastocyst embryos. The dataset includes ploidy status, morphokinetic features, morphology grades, and 11 clinical variables. Six machine learning (ML) models including Random Forest (RF), Linear Discriminant Analysis (LDA), Logistic Regression (LR), Support Vector Machine (SVM), AdaBoost (ADA), and Light Gradient-Boosting Machine (LGBM) were trained to predict ploidy status probabilities across three distinct datasets: high-grade embryos (HGE, n = 1107), low-grade embryos (LGE, n = 364), and all-grade embryos (AGE, n = 1471). The model's performance was interpreted using XAI, including SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME) techniques. RESULTS: The mean maternal age was 38.5 ± 3.85 years. The Random Forest (RF) model exhibited superior performance compared to the other five ML models, achieving an accuracy of 0.749 and an AUC of 0.808 for AGE. In the external test set, the RF model achieved an accuracy of 0.714 and an AUC of 0.750 (95% CI, 0.702-0.796). SHAP's feature impact analysis highlighted that maternal age, paternal age, time to blastocyst (tB), and day 5 morphology grade significantly impacted the predictive model. In addition, LIME offered specific case-ploidy prediction probabilities, revealing the model's assigned values for each variable within a finite range. CONCLUSION: The model highlights the potential of using XAI algorithms to enhance ploidy prediction, optimize embryo selection as patient-centric consultation, and provides reliability and transparent insights into the decision-making process.

Disease diagnosis and arthroplasty type are strongly associated with short-term postoperative patient-reported outcomes in patients undergoing primary total shoulder arthroplasty.

BACKGROUND: Prognostic factors for total shoulder arthroplasty (TSA) clinical outcomes are incompletely understood. This study investigates the associations of preoperative patient, disease-specific, and surgical factors with 1-year postoperative PENN Shoulder Score (PSS) in patients undergoing primary TSA. METHODS: Cleveland Clinic patients undergoing primary anatomic TSA (aTSA) or reverse TSA (rTSA) for glenohumeral osteoarthritis (GHOA) or rotator cuff tear arthropathy (CTA) between February 2015 and August 2019, and having complete preoperative and 1-year postoperative patient-reported outcome measures (PROMs), were included. Twenty preselected preoperative patient, disease-specific, and surgical factors were used to fit multivariable models for 1-year PSS and its subscores. RESULTS: Of 1427 eligible primary TSAs, 1174 had 1-year follow-up by PROMs (82%), with 1042 analyzed after additional exclusions, including 30% rTSAs for CTA (n = 308), 26% rTSAs for GHOA (n = 275), and 44% aTSAs for GHOA (n = 459). All PROMs showed statistically significant improvements postoperatively, with 89% of patients reaching an acceptable symptom state. Lower 1-year PSS was associated with younger age, female sex, current smoking, chronic pain diagnosis, history of prior surgery, worker's compensation claim, lower preoperative mental health, lower baseline PSS, absence of glenoid bone loss, and diagnosis-arthroplasty type (CTA-rTSA < GHOA-rTSA < GHOA-aTSA). The most important prognostic factors associated with 1-year PSS were diagnosis-arthroplasty type, baseline mental health status, and insurance status. CONCLUSIONS: Disease diagnosis, arthroplasty type, and several other baseline factors are strongly and individually associated with PROMs following primary TSA, with patients undergoing aTSA for GHOA demonstrating the highest PROM scores at 1-year follow-up. Patient, disease-specific, and surgical factors can be used to guide postoperative prognosis following primary TSA for improved preoperative patient counseling regarding expected outcomes of these procedures.

Repeat resection for recurrent glioblastoma in the temozolomide era: a real-world multi-centre study.

INTRODUCTION: In contrast to standard-of-care treatment of newly diagnosed glioblastoma, there is limited consensus on therapy upon disease progression. The role of resection for recurrent glioblastoma remains unclear. This study aimed to identify factors for overall survival (OS) and post-progression survival (PPS) as well as to validate an existing prediction model. METHODS: This was a multi-centre retrospective study that reviewed consecutive adult patients from 2006 to 2019 that received a repeat resection for recurrent glioblastoma. The primary endpoint was PPS defined as from the date of second surgery until death. RESULTS: 1032 glioblastoma patients were identified and 190 (18%) underwent resection for recurrence. Patients that had second surgery were more likely to be younger (<70 years) (adjusted OR: 0.3; 95% CI: 0.1-0.6), to have non-eloquent region tumours (aOR: 1.7; 95% CI: 1.1-2.6) and received temozolomide chemoradiotherapy (aOR: 0.2; 95% CI: 0.1-0.4). Resection for recurrent tumour was an independent predictor for OS (aOR: 1.5; 95% CI: 1.3-1.7) (mOS: 16.9 months versus 9.8 months). For patients that previously received temozolomide chemoradiotherapy and subsequent repeat resection (137, 13%), the median PPS was 9.0 months (IQR: 5.0-17.5). Independent PPS predictors for this group were a recurrent tumour volume of >50cc (aOR: 0.6; 95% CI: 0.4-0.9), local recurrence (aOR: 1.7; 95% CI: 1.1-3.3) and 5-ALA fluorescence-guided resection during second surgery (aOR: 1.7; 95% CI: 1.1-2.8). A National Institutes of Health Recurrent Glioblastoma Multiforme Scale score of 0 conferred an mPPS of 10.0 months, a score of 1-2, 9.0 months and a score of 3, 4.0 months (log-rank test, p-value < 0.05). CONCLUSION: Surgery for recurrent glioblastoma can be beneficial in selected patients and carries an acceptable morbidity rate. The pattern of recurrence influenced PPS and the NIH Recurrent GBM Scale was a reliable prognostication tool.

COVID-19 is Affecting the Presentation and Treatment of Melanoma Patients in the Northeastern United States.

BACKGROUND: Covid-19 significantly affected healthcare delivery over the past year, with a shift in focus away from nonurgent care. Emerging data are showing that screening for breast and colon cancer has dramatically decreased. It is unknown whether the same trend has affected patients with melanoma. METHODS: This is a retrospective cohort study of melanoma patients at two large-volume cancer centers. Patients were compared for 8 months before and after the lockdown. Outcomes focused on delay in treatment and possible resultant upstaging of melanoma. RESULTS: A total of 375 patients were treated pre-lockdown and 313 patients were treated post-lockdown (17% decrease). Fewer patients presented with in situ disease post-lockdown (15.3% vs. 17.9%), and a higher proportion presented with stage III-IV melanoma (11.2% vs. 9.9%). Comparing patients presenting 2 months before versus 2 months after the lockdown, there was an even more significant increase in Stage III-IV melanoma from 7.1% to 27.5% (p < 0.0001). Finally, in Stage IIIB-IIID patients, there was a decrease in patients receiving adjuvant therapy in the post lockdown period (20.0% vs. 15.2%). CONCLUSIONS: As a result of the recent pandemic, it appears there has been a shift away from melanoma in situ and toward more advanced disease, which may have significant downstream effects on prognosis and could be due to a delay in screening. Significantly patients have presented after the lockdown, and fewer patients are undergoing the recommended adjuvant therapies. Patient outreach efforts are essential to ensure that patients continue to receive preventative medical care and screening as the pandemic continues.

Thyroid autoimmunity is associated with higher risk of premature ovarian insufficiency-a nationwide Health Insurance Research Database study.

STUDY QUESTION: Is thyroid autoimmunity associated with a higher risk of low ovarian reserve and POI? SUMMARY ANSWER: Thyroid autoimmunity significantly increases the risk of POI in women. WHAT IS KNOWN ALREADY: POI is closely related with autoimmune disease, and according to some studies, thyroid autoimmunity (TAI) may account for diminished ovarian reserve. However, no large-scale cohort study has demonstrated the association between TAI and POI. STUDY DESIGN, SIZE, DURATION: A longitudinal population-based retrospective cohort study on the National Health Insurance Research Database (NHIRD) was designed. Since 1 March 1995, the National Health Insurance (NHI) programme in Taiwan has included 99.9% of the 23 million population of Taiwan. Patients between 1 January 2000 and 31 December 2012 were eligible for recruitment, and 21 325 subjects were analysed in our study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two cohorts, Hashimoto's and Grave's disease, were composed of patients with autoimmune thyroid disease between 20 and 40 years of age. The comparison cohorts consisted of patients in the NHIRD without autoimmune thyroid disease matched by age at a ratio of 1:4 in subject numbers. MAIN RESULTS AND THE ROLE OF CHANCE: The Hashimoto's disease (HD) cohort, Grave's disease (GD) cohort and two comparison cohorts were followed up until a diagnosis of amenorrhoea, menopausal syndrome, other ovarian failure or infertility due to ovarian failure had been made. Compared statistically with the non-HD cohort, patients with HD exhibited an 89% higher risk of amenorrhoea (95% CI =1.36-2.61). The HD patients exhibited a 2.40-fold higher risk of infertility due to ovarian failure than the non-HD subjects (hazard ratio (HR)=2.40, 95% confidence interval (CI)=1.02-5.68). In comparison with the non-GD cohort, patients with GD exhibited a 68% higher risk of amenorrhoea (95% CI = 1.43-1.98) after adjustment. According to the Kaplan-Meier analysis, the cumulative incidence of amenorrhoea and menopausal syndrome was significantly higher in the TAI groups than in the control groups. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective study using ICD-9 disease code analysis to determine the statistical association between two diseases. WIDER IMPLICATIONS OF THE FINDINGS: Given that autoimmune thyroid disease is highly associated with early diminished ovarian reserve or even premature ovarian failure or POI, the options for infertility treatment may be re-directed to more efficient methods in infertile patients diagnosed with the disease. If the ovarian reserve is normal at the time of diagnosis of thyroid autoimmune disease, close follow-up of ovarian reserve may be highly recommended. STUDY FUNDING/COMPETING INTEREST(S): This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center, Grant Number: MOHW109-TDU-B-212-114004. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Central-peg radiolucency progression of an all-polyethylene glenoid with hybrid fixation in anatomic total shoulder arthroplasty is associated with clinical failure and reoperation.

BACKGROUND: Glenoid component loosening is a common cause of failure after anatomic total shoulder arthroplasty. Prior studies of all-polyethylene glenoid implants with hybrid fixation did not show early glenoid radiolucency to be clinically significant. The purpose of this study was to determine the clinical significance of progression of radiolucency around the central peg of the glenoid component. METHODS: We identified 73 shoulders that underwent primary anatomic total shoulder arthroplasty between January 1995 and May 2015 for osteoarthritis with an all-polyethylene pegged glenoid, with a minimum follow-up interval of 2 years between early and late follow-up. Demographic, radiographic (central-peg osteolysis [CPO] and central-peg grading [CPG]), and outcome variables comprising the Penn Shoulder Score (PSS) and revision surgery were collected. Clinical failure was defined as a PSS decrease >11.4 points (ie, PSS failure) or revision surgery. RESULTS: The average patient age at surgery was 65 ± 7 years, and 63% of patients were men. The median initial follow-up period was 14 months (interquartile range, 12-25 months), and the final median follow-up period was 56 months (interquartile range, 47-69 months). Revision surgical procedures were performed in 4 patients, and 17 PSS failures occurred. We found that CPO at final follow-up, CPG progression, and worse PSS at follow-up were associated with revision surgery (P < .05). We also found younger age at surgery, CPO at final follow-up, CPG progression, and greater glenoid component retroversion at final follow-up to be associated with clinical failure (PSS failure or revision surgery) (P < .05). Multivariate analysis found only CPG progression to be associated with clinical failure (P < .001). DISCUSSION AND CONCLUSION: CPO and CPG progression were associated with clinical failure, defined as decreasing clinical outcome scores or revision surgery.

Inter-rater agreement of rotator cuff tendon and muscle magnetic resonance imaging parameters evaluated preoperatively and during the first postoperative year following rotator cuff repair.

BACKGROUND: Magnetic resonance imaging (MRI) is standard of care for rotator cuff evaluation, with clinical interpretation usually limited to qualitative judgments. The reliability of MRI-based measurements and scoring systems has been evaluated only preoperatively or ≥6 months following rotator cuff repair, when repairs are in the later stages of healing. This study describes the MRI assessments and inter-rater agreement of various rotator cuff tendon and muscle parameters evaluated preoperatively and 4 times during the first postoperative year. METHODS: Two musculoskeletal radiologists independently assessed MRI scans of 42 patients preoperatively and 3, 12, 26, and 52 weeks after rotator cuff repair. Using standardized reading rules, readers assessed tendon integrity (5-point Sugaya classification), tear dimensions, muscle fat (5-point Goutallier classification) and atrophy (4-point Warner classification), muscle cross-sectional areas, and myotendinous junction distance. Raw exact agreement proportions, κ statistics, and correlation coefficients were used to quantify inter-rater agreement. RESULTS: Readers showed moderate to substantial above-chance agreement in scoring rotator cuff tendon integrity and supraspinatus muscle atrophy and good to excellent agreement on tear dimensions and muscle cross-sectional areas but only fair to moderate agreement for fatty infiltration and myotendinous junction distance. Only fatty infiltration grades evidenced observer bias. Inter-rater agreement did not appear time dependent. CONCLUSION: By use of defined reading rules in a research setting, MRI evaluations of rotator cuff tendon integrity, tear dimensions, muscle atrophy, and cross-sectional areas have reasonable reliability at all time points in the first postoperative year. However, the presence of clinically significant disagreements, even in such favorable circumstances, indicates the need for improved imaging tools for precise rotator cuff evaluation.

Radiotherapy-induced glioblastoma: distinct differences in overall survival, tumor location, pMGMT methylation and primary tumor epidemiology in Hong Kong chinese patients.

INTRODUCTION: Radiotherapy-induced glioblastomas (RIGB) are a well-known late and rare complication of brain irradiation. Yet the clinical, radiological and molecular characteristics of these tumors are not well characterized. METHODS: This was a retrospective multicentre study that analysed adult patients with newly diagnosed glioblastoma over a 10-year period. Patients with RIGB were identified according to Cahan's criteria for radiation-induced tumors. A case-control analysis was performed to compare known prognostic factors for overall survival (OS) with an independent cohort of IDH-1 wildtype de novo glioblastomas treated with standard temozolomide chemoradiotherapy. Survival analysis was performed by Cox proportional hazards regression. RESULTS: A total of 590 adult patients were diagnosed with glioblastoma. 19 patients (3%) had RIGB. The mean age of patients upon diagnosis was 48 years ± 15. The mean latency duration from radiotherapy to RIGB was 14 years ± 8. The mean total dose was 58Gy ± 10. One-third of patients (37%, 7/19) had nasopharyngeal cancer and a fifth (21%, 4/19) had primary intracranial germinoma. Compared to a cohort of 146 de novo glioblastoma patients, RIGB patients had a shorter median OS of 4.8 months versus 19.2 months (p-value: <.001). Over a third of RIGBs involved the cerebellum (37%, 7/19) and was higher than the control group (4%, 6/146; p-value: <.001). A fifth of RIGBs (21%, 3/19) were pMGMT methylated which was significantly fewer than the control group (49%, 71/146; p-value: .01). For RIGB patients (32%, 6/19) treated with re-irradiation, the one-year survival rate was 67% and only 8% for those without such treatment (p-value: .007). CONCLUSION: The propensity for RIGBs to develop in the cerebellum and to be pMGMT unmethylated may contribute to their poorer prognosis. When possible re-irradiation may offer a survival benefit. Nasopharyngeal cancer and germinomas accounted for the majority of original malignancies reflecting their prevalence among Southern Chinese.

Midterm outcomes of arthroscopic rotator cuff repair in patients aged 75 years and older.

BACKGROUND: Full-thickness rotator cuff tears remain a significant cause of pain and dysfunction in the elderly. Substantial improvement in pain and functional outcomes with arthroscopic cuff repair is possible. Recent data has shown that patients older than 70-75 years still have clinical improvement with operative rotator cuff repair. MATERIALS AND METHODS: This is a retrospective study of patients aged ≥75 years undergoing arthroscopic rotator cuff repair at a minimum of 24 months after surgery. Outcome measurements included range of motion (ROM), visual analog scale (VAS) pain scores, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores, Single Assessment Numeric Evaluation (SANE) scores, and Short Form Health Survey (SF-12) scores. Reoperation and rates of conversion to reverse shoulder arthroplasty (RSA) were determined. RESULTS: Eighty-three patients were included with an average follow-up of 56.9 ± 25.9 months (range 24-127 months). Six (7.2%) patients had additional surgery, including 3 revision rotator cuff repairs for retear, 2 conversion to RSA, and 1 capsular release and loose anchor removal. There were statistically significant improvements in shoulder ROM, ASES, SANE, VAS, and SF-12 scores postoperatively. CONCLUSION: Rotator cuff repair in select patients aged ≥75 years results in reliable improvements in pain and function. There was a low reoperation rate or conversion to RSA (7.2%) at midterm follow-up. This study indicates a role for rotator cuff repair in an elderly population and argues against the routine use of reverse arthroplasty for repairable rotator cuff tears in this population.

Arthroscopic débridement of irreparable rotator cuff tears: predictors of failure and success.

HYPOTHESIS/BACKGROUND: Many techniques have been described to treat irreparable rotator cuff tears (RCT). Arthroscopic débridement for massive, irreparable RCT has been previously described to be a successful operation. The primary objective of our study was to analyze the mid-term outcomes and failure rates of arthroscopic débridement for irreparable RCTs and identify risk factors associated with failure and poor outcomes. METHODS: We retrospectively identified all patients between 2008 and 2013 who underwent arthroscopic débridement for an irreparable RCT. Demographics, operative reports, and preoperative imaging were collected from the medical record and outcome scores (American Shoulder and Elbow Surgeons [ASES] and visual analog scale) were collected at a minimum of 5-year follow-up. RESULTS: Twenty-six patients were included with a median follow-up of 98 months (range, 58-115 months). The average age at the time of surgery was 60 ± 11 years. Six patients (23%) had a reoperation at a median 11 months (range, 1-91 months), with 5 of those being revised to reverse shoulder arthroplasty. Median ASES and visual analog scale pain scores improved significantly from preoperatively to postoperatively (P < .01). Lower preoperative forward elevation was associated with worse postoperative ASES scores (P = .004) and revision to reverse shoulder arthroplasty. We found no associations between preoperative radiographic variables and reoperation or lower outcome scores. DISCUSSION/CONCLUSION: Arthroscopic débridement for irreparable RCT shows good mid-term success with improvements in patient-reported outcome scores and pain. Cost-effectiveness of more expensive procedures should be considered in the context of these successful results. Poor preoperative forward elevation appears to be a negative predictor of outcome and should be considered carefully when indicating patients for this procedure.

Early radiographic failure of reverse total shoulder arthroplasty with structural bone graft for glenoid bone loss.

INTRODUCTION: Structural glenoid bone grafting in reverse total shoulder arthroplasty (RSA) has previously been reported to have good functional outcomes and low complication rates. We have observed different complication rates and hypothesized that baseplate fixation and severity of deformity may be predictors of early failure. METHODS: We retrospectively identified 44 patients who underwent RSA with structural bone grafting for glenoid bone defects. All patients had preoperative and postoperative (Grashey and axillary) radiographs at a minimum of 1 year after surgery and within 3 months of surgery for evaluation of implant and graft positioning. Clinical data and outcome scores were collected at the same intervals. RESULTS: There were 61% females and 39% males, with an average age of 74 ± 8 years at the time of surgery. The median final radiographic follow-up was 20 months, with 37 primary RSA and 7 revision RSA. Graft resorption was found in 11 of 44 patients (25%), and radiographic failure was found in 11 of 44 patients (25%) at a median of 8 months (range 3-51 months). Forward elevation, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation (SANE), and Simple Shoulder Test (SST) scores all significantly improved postoperatively (P < .0001). Radiographic baseplate failure was associated with graft resorption (P = .002), more retroversion correction (P = .02), and worse SANE scores at final follow-up (P = .01). DISCUSSION/CONCLUSION: RSA with structural bone graft improved range of motion and function, but there was a larger than previously reported baseplate loosening rate. This early radiographic loosening appeared to be associated with graft resorption, retroversion correction, and worse outcome scores.

Long-term use of low-dose aspirin for cancer prevention: A 10-year population cohort study in Hong Kong.

Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, has been found to possess protective effects against cancer development in the Western populations. Such effects among Asian populations remain uncertain. The objective of this study is to investigate the use of aspirin on prevention of different cancers among Chinese users. This population-based study utilized database from the Hong Kong Hospital Authority; adults with aspirin prescription for at least 6 months between 2000 and 2004 were included and followed up until 2013. Aspirin users were age-sex matched with non-aspirin users at a 1:2 ratio. Incidences of cancer were the primary outcome measured by relative risk (RR). A total of 204,170 aspirin users and 408,339 non-aspirin users were included, with the mean age 67.5 years, 7.7 years average duration of aspirin prescription and 80 mg as the median dose of aspirin. Cancer incidences were found in 26,929 (13.2%) aspirin users and 70,755 (17.3%) non-aspirin users. Compared with patients who had not been prescribed aspirin, aspirin usage led to significant reduction of cancers in liver (RR: 0.49), stomach (RR: 0.42), colorectum (RR: 0.71), lung (RR: 0.65), pancreas (RR: 0.54), oesophagus (RR: 0.59) and leukaemia (RR: 0.67). There was no demonstrable reduction of kidney cancer, bladder cancer, prostate cancer and multiple myeloma in association with the usage of aspirin. Risk of breast cancer was shown to marginally increase (RR: 1.14) with aspirin usage. This study demonstrated that the long-term use of low-dose aspirin is associated with the reduction in risk of various cancers but not for breast cancer. Further investigation is needed before promoting aspirin as a primary chemoprotective agent.

Low-dose aspirin can reduce colorectal cancer mortality after surgery: A 10-year follow-up of 13 528 colorectal cancer patients.

BACKGROUND AND AIM: The chemopreventive effect of aspirin in colorectal cancer (CRC) is well studied, but its benefit in patients after CRC diagnosis and surgery is unclear. This study aims to investigate the effects of low-dose aspirin use in mortality among CRC patients after surgery. METHODS: Patients were analyzed in two cohorts: (i) patients taking aspirin before CRC diagnosis and continued or discontinued aspirin after surgery and (ii) patients, who never used aspirin before CRC diagnosis, received or did not receive aspirin after surgery. CRC-related mortality and all-cause mortality were the primary and secondary outcomes. Sub-distribution hazard ratio (SHR) for competing-risk CRC mortality was fitted to adjust for other causes of death; hazard ratio (HR) was used to compare all-cause mortality. RESULTS: A total of 13 528 CRC patients were included. Among 3292 patients with regular aspirin use before CRC diagnosis, 2658 (80.7%) continued aspirin and 634 (19.3%) discontinued aspirin after surgery. Continuous use of aspirin significantly reduced CRC-related mortality (SHR: 0.69, 95% confidence interval [CI]: 0.59-0.81) and all-cause mortality (HR: 0.61, 95% CI: 0.55-0.68). Among 10 236 patients who did not use aspirin before CRC diagnosis, 1054 patients (10.3%) received aspirin after surgery and 9182 (89.7%) did not. Aspirin initiated after surgery reduced CRC-related mortality (SHR: 0.88, 95% CI: 0.80-0.98) and all-cause mortality (HR: 0.87, 95% CI: 0.81-0.94). CONCLUSIONS: Irrespective of aspirin use before surgery for CRC, low-dose aspirin after surgery lowers risk of both CRC-related mortality and overall mortality.

Comparison of radiographic and clinical outcomes of revision reverse total shoulder arthroplasty with structural versus nonstructural bone graft.

BACKGROUND: Revision shoulder arthroplasty in the setting of glenoid bone loss poses substantial surgical challenges. This study's purpose was to compare radiographic and clinical results of patients requiring structural iliac crest bone autograft (ICBA) for severe bone loss versus patients with less severe bone loss treated with nonstructural bone allograft (NSBA) in the setting of revision reverse total shoulder arthroplasty (RSA). METHODS: A retrospective cohort of 30 patients (70% of the 43 patients who met the inclusion criteria) undergoing revision RSA with ICBA (n = 15) or NSBA (n = 15) between 2007 and 2015 were analyzed at a minimum 2-year follow-up. Radiographic assessment included bone graft integration, bone graft resorption, glenosphere tilt, glenosphere version, and the presence of scapular notching. Clinical assessment included active range of motion, Penn Shoulder Score, Veterans RAND 12-item health survey, and need for revision surgery. RESULTS: No radiographic difference was found between the ICBA and NSBA groups with regard to implant position, graft integration, scapular notching, implant shift, or failure of fixation (P > .05). Of 15 patients with ICBA, 14 (93%) had at least partial integration of the bone graft. Some degree of resorption of the bone graft was noted in 6 of 15 patients (40%). There was no significant difference in postoperative active range of motion, Penn Shoulder Score, or Veterans RAND 12-item health survey score (P > .05 for all comparisons). One patient in the ICBA group underwent revision surgery for glenoid baseplate failure. CONCLUSION: Revision RSA with glenoid bone grafting resulted in good clinical and radiographic outcomes at short-term follow-up. Patients requiring structural ICBA were not at increased risk of component failure, radiographic or clinical complications, or inferior clinical outcomes.

A rare cause of sciatica discovered during digital rectal examination: case report of an intrapelvic sciatic notch schwannoma.

Intrapelvic sciatic nerve schwannomas are rare causes for non-discogenic sciatica. We describe a 44-year-old female who had a palpable mass on digital rectal examination that exhibited a positive Tinel's sign. The schwannoma was excised by a posterior transgluteal approach. Patients with negative spinal imaging should undergo pelvic scanning to rule out these tumors.

Short androgen receptor poly-glutamine-promoted endometrial cancer is associated with benzo[a]pyrene-mediated aryl hydrocarbon receptor activation.

The androgen receptor (AR) poly-glutamine polymorphism (AR-Q) was reported to play role in endometrial cancer (EMCA) development, yet controversial. Environmental factors interact with genetic variation have been reported in EMCA. Aerosol toxins, polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP), are EMCA facilitators. This report examined the interplay between AR-Qs and BaP in EMCA. During analysing patient AR-Q polymorphism and Aryl hydrocarbon Receptor (AhR) expressions, we found overall survival (OS) benefit is ascending with AR-Q lengths (5-year OS of 61.3% in Q length <20 and 88% in Q length >23). And AhR is higher expressed in short AR-Q tumour compared to that in long AR-Q patient. In vitro study found androgen-response element (ARE) activity descends with AR-Qs length (Q13 > Q25 > Q35), whereas BaP suppresses ARE activities in EMCA cells. Furthermore, AR-Q13 (but not AR-Q25, or -35) enhances BaP-induced dioxin-responsive element (DRE) activity. Lastly, AR-Q13 exerts higher colony-forming capacity than other AR-Qs, and knock-down AhR abolished AR-Q13-mediated colony numbers. This study demonstrated a possible interaction of gene (AR-Q polymorphism) and environmental toxins (e.g. BaP) to affect cancer progression. A large-scale epidemiology and public health survey on the interaction of environmental toxin and AR poly-Q in EMCA is suggested.

Dsc E3 ligase localization to the Golgi requires the ATPase Cdc48 and cofactor Ufd1 for activation of sterol regulatory element-binding protein in fission yeast.

Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases associated with diverse cellular activities (AAA+) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released into the cytosol to enter the nucleus and regulate gene expression. Previously, we reported that Cdc48 binding to Rbd2 is required for Rbd2-mediated SREBP cleavage. Here, using affinity chromatography and mass spectrometry experiments, we identified Cdc48-binding proteins in S. pombe, generating a list of many previously unknown potential Cdc48-binding partners. We show that the established Cdc48 cofactor Ufd1 is required for SREBP cleavage but does not interact with the Cdc48-Rbd2 complex. Cdc48-Ufd1 is instead required at a step prior to Rbd2 function, during Golgi localization of the Dsc E3 ligase complex. Together, these findings demonstrate that two distinct Cdc48 complexes, Cdc48-Ufd1 and Cdc48-Rbd2, are required for SREBP activation and low-oxygen adaptation in S. pombe.

Improved, Shorter-Latency Carcinogen-Induced Hepatocellular Carcinoma Model in Pigs.

Large animal models are important tools for hepatocellular carcinoma (HCC) research, especially in studies of hepatic vasculature, interventional techniques, and radiofrequency or microwave hyperthermia. Currently, diethylnitrosamine (DENA)-induced HCC in pigs is the only large animal model for in situ HCC with a tumor latency of 10-26 months. While phenobarbital (PB) is often used to accelerate DENA-induced HCC in rodents, it has not been previously studied in the porcine model. Therefore, we hypothesize that the addition of PB in the DENA-induced HCC porcine model will accelerate tumor latency compared to DENA alone. HCC and benign lesions were seen on serial MRI and confirmed on histopathology. Liver and tumors were further characterized by CT angiography, vascular corrosion casting, and permittivity measurements.

Intraventricular urokinase to treat a blocked ventriculoperitoneal shunt in a glioblastoma patient with leptomeningeal spread.

Leptomeningeal spread and hydrocephalus are increasingly recognized as late disease complications of glioblastoma with almost a quarter of patients requiring early cerebrospinal fluid shunting. The neurosurgeon is challenged with maintaining shunt patency when tumor disease progression is rapid and adjuvant oncologic therapy has yet to be initiated. We describe our experience in treating a young female with diffuse glioblastoma leptomeningeal spread and communicating hydrocephalus who had several episodes of shunt obstruction due to intraluminal tumor cell-fibrin deposits. Regular intraventricular instillations of urokinase fibrinolytic therapy not only re-established shunt patency but also contributed to the resolution of her hydrocephalus.