The Histone Chaperone FACT Induces Cas9 Multi-turnover Behavior and Modifies Genome Manipulation in Human Cells.

Cas9 is a prokaryotic RNA-guided DNA endonuclease that binds substrates tightly in vitro but turns over rapidly when used to manipulate genomes in eukaryotic cells. Little is known about the factors responsible for dislodging Cas9 or how they influence genome engineering. Unbiased detection through proximity labeling of transient protein interactions in cell-free Xenopus laevis egg extract identified the dimeric histone chaperone facilitates chromatin transcription (FACT) as an interactor of substrate-bound Cas9. FACT is both necessary and sufficient to displace dCas9, and FACT immunodepletion converts Cas9's activity from multi-turnover to single turnover. In human cells, FACT depletion extends dCas9 residence times, delays genome editing, and alters the balance between indel formation and homology-directed repair. FACT knockdown also increases epigenetic marking by dCas9-based transcriptional effectors with a concomitant enhancement of transcriptional modulation. FACT thus shapes the intrinsic cellular response to Cas9-based genome manipulation most likely by determining Cas9 residence times.

Comparing resident operative volumes for routine general surgery cases at academic, urban community, and rural training sites.

BACKGROUND: Surgical training traditionally took place at academic centres, but changed to incorporate community and rural hospitals. As little data exist comparing resident case volumes between these locations, the objective of this study was to determine variations in these volumes for routine general surgery procedures. METHODS: We analyzed senior resident case logs from 2009 to 2019 from a general surgery residency program. We classified training centres as academic, community, and rural. Cases included appendectomy, cholecystectomy, hernia repair, bowel resection, adhesiolysis, and stoma formation or reversal. We matched procedures to blocks based on date of case and compared groups using a Poisson mixed-methods model and 95% confidence intervals (CIs). RESULTS: We included 85 residents and 28 532 cases. Postgraduate year (PGY) 3 residents at academic sites performed 10.9 (95% CI 10.1-11.6) cases per block, which was fewer than 14.7 (95% CI 13.6-15.9) at community and 15.3 (95% CI 14.2-16.5) at rural sites. Fourth-year residents (PGY4) showed a greater difference, with academic residents performing 8.7 (95% CI 8.0-9.3) cases per block compared with 23.7 (95% CI 22.1-25.4) in the community and 25.6 (95% CI 23.6-27.9) at rural sites. This difference continued in PGY5, with academic residents performing 8.3 (95% CI 7.3-9.3) cases per block, compared with 18.9 (95% CI 16.8-21.0) in the community and 14.5 (95% CI 7.0-21.9) at rural sites. CONCLUSION: Senior residents performed fewer routine cases at academic sites than in community and rural centres. Programs can use these data to optimize scheduling for struggling residents who require exposure to routine cases, and help residents complete the requirements of a Competence by Design curriculum.

Knowledge and attitudes towards eating disorders: A survey of psychiatrists and psychiatry trainees in New South Wales.

OBJECTIVE: To evaluate New South Wales (NSW) psychiatrists' and psychiatry trainees' knowledge and attitudes towards eating disorders (EDs). METHOD: A total of 1781 psychiatrists and trainees in NSW were invited to complete an anonymous questionnaire assessing ED confidence, knowledge and attitudes. RESULTS: A total of 51 doctors responded to the survey, with 38 completing all items. Significant knowledge gaps were revealed. Respondents expressed a desire for more ED training. CONCLUSION: Enhanced ED training in psychiatry education and incorporating the lived experience voice to improve attitudes appear necessary.

Prediction of successful veno-venous extracorporeal life support liberation using the oxygen challenge test.

BACKGROUND: The oxygen challenge test (OCT) is an underutilized measure of lung recovery, easily performed prior to proceeding with a trial-off V-V ECLS as part of a weaning algorithm. Evidence-based thresholds for OCT results which support continuing with V-V ECLS weaning are lacking, making interpretation of these tests challenging in clinical practice. METHODS: We performed a retrospective review of patients commenced on V-V ECLS as a bridge-to-recovery at Vancouver General Hospital from 2015-2019. The absolute PaO2 post-OCT and change in PaO2 proportional to incremental FiO2 change on the ventilator (∆PaO2 ) were evaluated as predictive screening metrics for identifying conditions favorable for successful trial-off of V-V ECLS. RESULTS: An optimal cut-off of PaO2 ≥ 240 mm Hg post-OCT (AUC 0.77) and ∆PaO2 ≥ 250 mm Hg (AUC 0.76) was identified as a threshold for predicting successful trials-off. A total of 26 and 24 patients achieved post-OCT PaO2 and ∆PaO2 thresholds, and 100% of these patients were liberated successfully from ECLS during their admission. CONCLUSIONS: The OCT can serve as an effective screen of shunt reduction and native lung recovery which can be used alongside other measures of ventilation to assess for suitability of liberation from V-V ECLS prior to a trial-off. Achieving a PaO2 ≥ 240 mm Hg post-OCT is a strong prognostic indicator for successful liberation from V-V ECLS during ICU admission.

Patient, operative and pain management factors influencing inpatient compared with surgical day care mastectomy procedures at a community hospital.

BACKGROUND: The COVID-19 pandemic highlighted the importance of maximizing same-day discharge after surgery to mitigate potential patient harms associated with inpatient admission and conserve valuable hospital resources. Adoption of same-day discharge after breast surgery, particularly mastectomy, has been slow despite recent research suggesting the physical and psychological benefits of same-day discharge after surgery. We sought to identify factors associated with inpatient compared with surgical day care mastectomy procedures at a community hospital in Vernon, British Columbia. METHODS: We conducted a retrospective chart review of all patients who underwent a total mastectomy without reconstruction at Vernon Jubilee Hospital, a 196-bed community hospital, between April 2016 and March 2019. Patient characteristics, operative variables and pain management were compared between inpatient and surgical day care mastectomy procedures. We also compared 7-day readmission, reoperation and complications. RESULTS: A total of 187 mastectomy patients were analyzed with 72 (38.5%) surgical day care procedures. Factors associated with inpatient procedures included longer operative time (66.1 min v. 53.5 min, p = 0.001), bilateral mastectomy (91% v. 9%, p = 0.01) and suspected or confirmed obstructive sleep apnea (32% v. 17%, p = 0.04). Preoperative acetaminophen (83% v. 17%, p < 0.001), multilevel intercostal block (83% v. 17%, p < 0.001) and a prescription for acetaminophen plus tramadol (58% v. 42%, p < 0.001) were associated with day care surgeries. There were no significant differences between the inpatient and surgical day care groups with respect to 7-day readmission, reoperation or postoperative complications. CONCLUSION: We found no significant differences in surgical outcomes between inpatients and those with same-day discharge after mastectomy procedures. These findings add to the growing body of evidence that surgical day care mastectomy procedures are safe in the community setting.

Excision of breast fibroepithelial lesions: when is it still necessary?-A 10-year review of a regional centre.

PURPOSE: Fibroepithelial lesions (FEL) range from benign fibroadenoma (FA) to malignant phyllodes tumor (PT), but can be difficult to diagnose on core needle biopsy (CNB). This study assesses risk factors for phyllodes tumor (PT) and recurrence and whether a policy to excise FELs over 3 cm in size is justified. METHODS: Patients having surgery for FELs from 2009 to 2018 were identified. The association of clinical, radiology and pathological features with PT and recurrence were evaluated. Trend analysis was used to assess risk of PT based on imaging size. RESULTS: Of the 616 patients with FELs, 400 were identified as having FA on CNB and 216 were identified as having FEL with a comment of concern for phyllodes tumor (query PT, QPT). PT was identified in 107 cases; 28 had CNB of FA (7.0%), while 79 had QPT (36.6%). Follow-up was available for 86 with a mean of 56 months; six patients had recurrence of PT, all of whom had QPT on CNB. The finding of PT was associated with CNB of QPT, increasing age and size on multivariate logistic regression. All patients diagnosed with PT following CNB of FA had enlarging lesions with a mean size of 38.3 mm. CONCLUSIONS: Our data does not support routine excision of FELs based on size alone. All patients with QPT on CNB, regardless of size should consider excision due to high risk of PT and recurrence, and the decision to excise FAs to rule out PT should also consider whether the lesion is enlarging.

The Breast Cancer Patient Experience of Telemedicine During COVID-19.

BACKGROUND: The COVID-19 pandemic has seen major shifts in the delivery of health care across the world, including adoption of telemedicine. We present a survey of patient experience with telemedicine for the treatment of breast cancer. METHODS: A questionnaire designed to assess patient satisfaction with telemedicine was distributed to all patients who underwent surgery at the Providence Breast Centre (PBC) for breast cancer or benign/high-risk lesions with surgery follow-up dates between October 13 and December 31, 2020. Surveys were conducted via phone or at in-person follow-ups. RESULTS: A total of 123 of 172 (72%) eligible patients completed the survey; 85% of these patients enjoyed their telemedicine consultation, 93% found there was enough time for dialogue, 66% would choose to have a telemedicine consultation again, 79% would recommend telemedicine at PBC to a friend or family member, and 92% found Zoom© easy to use. When asked whether they prefer a telemedicine initial consultation over an in-person, 28% of patients agreed. When patients are analyzed according to their home address, those more than 10-km away from PBC prefer telemedicine over in-person appointments (37%) more often than those who live less than 10-km away (23%) (p = 0.045). CONCLUSIONS: Patients report a high level of satisfaction with telemedicine. It may be worthwhile to continue telemedicine beyond the pandemic era, due to its convenience, efficiency, and low-cost while keeping patients, physicians, and office staff safe. It also may be more useful in large geographic areas, such as British Columbia to increase access to care.

Revisiting the effectiveness of repetitive transcranial magnetic stimulation treatment in depression, again.

Following on from the publication of the Royal Australian and New Zealand Journal of Psychiatry Mood Disorder Clinical Practice Guidelines (2020) and criticisms of how these aberrantly addressed repetitive transcranial magnetic stimulation treatment of depression, questions have continued to be raised in the journal about this treatment by a small group of authors, whose views we contend do not reflect the broad acceptance of this treatment nationally and internationally. In fact, the evidence supporting the use of repetitive transcranial magnetic stimulation treatment in depression is unambiguous and substantial, consisting of an extensive series of clinical trials supported by multiple meta-analyses, network meta-analysis and umbrella reviews. Importantly, the use of repetitive transcranial magnetic stimulation treatment in depression has also been subject to a series of health economic analyses. These indicate that repetitive transcranial magnetic stimulation is a cost-effective therapy and have been used in some jurisdictions, including Australia, in support of public funding. An argument has been made that offering repetitive transcranial magnetic stimulation treatment may delay potentially effective pharmacotherapy. In fact, there is considerably greater danger of the opposite happening. Repetitive transcranial magnetic stimulation is as, if not more effective, than antidepressant medication after two unsuccessful medication trials and should be a consideration for all patients under these circumstances where available. There is no meaningful ongoing debate about the use of repetitive transcranial magnetic stimulation treatment in depression - it is a safe, effective and cost-effective treatment.

Impact of new cancer therapies on outpatient treatment delivery for colorectal cancer: A population-based study.

We investigated the impact of new systemic therapies approved in Canada for colorectal cancer on the frequency, intensity and duration of oncology clinic and infusion visits over five treatment phases from diagnosis (P1, P3) to treatment (P2, P4) of primary and metastatic disease, respectively, and during the last 6 months of life (P5). In total, 15,157 adult patients with newly diagnosed colorectal cancer and referred between 2000 and 2012 to any cancer clinic in British Columbia, Canada, were included. Frequency, intensity and duration of medical oncology clinic visits (CVs), oncology infusions (OIs) and oncology prescriptions (OPs) were measured by treatment phase. Mean, total and adjusted total duration for CVs increased for P1-5. CVs increased in P1-5, and in P1-4 when adjusted by treatment length. Adjusted and unadjusted OIs decreased in P1 coinciding with the introduction of an oral treatment option, but increased in P2-5. Mean OI duration increased in P1-5, while total and adjusted total decreased in P1 and increased in P2-5. OPs increased in P2-4, but were unchanged in P1 and P5. Multi-fold increases in resources and time required per patient were also observed, which have significant implications for demand projections in cancer care planning and delivery. In conclusion, patients required more visits in almost all treatment phases, visits on average took longer and patients were in treatment for longer periods of time.

Socioeconomic status does not influence the presentation of patients with inguinal hernia at an urban Canadian teaching hospital.

BACKGROUND: Socioeconomic status (SES) has been shown to influence the outcomes of surgical pathologies in areas with unequal access to health care. The purpose of this study was to measure the effect of SES on the urgency for inguinal hernia repair in an area with purported equitable access to health care in the context of a universal health care system. METHODS: We included all adult patients who underwent surgical management of an inguinal hernia between 2012 and 2016 at 2 urban academic centres. We measured the SES using the Vancouver Area Neighbourhood Deprivation Index (VANDIX) score. RESULTS: We included 2336 patients: 98 emergency surgery and 294 elective surgery cases. We matched patients without replacement on age, sex and American Society of Anesthesiology score, using optimized propensity score matching at a ratio of 1 case to 3 controls. We found no significant correlation between lower SES and emergency surgical management (p = 0.122). Secondary analysis assessed the impact of SES on morbidity and length of stay. We found no significant difference in the rate of complications, length of stay and recurrence by SES category. Patients from lower SES brackets had increased odds for readmission (odds ratio 1.979; 95% confidence interval 1.111-4.318). CONCLUSION: We found no correlation between a low SES and the need for emergency inguinal hernia repair, but found an increased rate of readmission in patients from lower SES brackets. This finding should be further scrutinized through a deeper dive into the barriers to access to nonacute care settings, such as home care.

Population-based assessment of sentinel lymph node biopsy in the management of cutaneous melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) for melanoma plays a central role in determining prognosis and guiding treatment and surveillance strategies. Despite widely published guidelines for SLNB, variation exists in its use. We aimed to determine the frequency of and predictive factors for SLNB in patients with clinically node-negative melanoma in British Columbia. METHODS: A retrospective review was performed of patients with clinically node-negative melanoma diagnosed between January 2015 and December 2017. Patients included had a Breslow depth greater than 0.75 mm or a Breslow depth less than or equal to 0.75 mm with ulceration, or a mitotic rate greater than or equal to 1/mm2. SLNB was considered to be indicated for clinical stages IB to IIC (American Joint Committee on Cancer's AJCC Cancer Staging Manual, seventh edition). RESULTS: A total of 759 patients were included. SLNB was performed in 54.8% (363/662) of patients when indicated. SLNB was more likely to be performed for tumours with a Breslow depth greater than 1.0 mm or a mitotic rate greater than or equal to 1/mm2. SLNB was less likely to be performed in patients older than 75 years and with a nonextremity tumour location. Compliance with SLNB guidelines decreased distant recurrence but did not significantly affect regional recurrence, nor did it have a significant impact on overall survival among patients aged 75 years and younger. CONCLUSION: SLNB is being underutilized in British Columbia. These results are concerning and highly relevant given the rapidly evolving field of adjuvant systemic therapy for high-risk patients and the increased proportion of patients who should be considered for SLNB on the basis of the eighth edition of the AJCC Cancer Staging Manual and current guidelines. Efforts should be made to increase the use of SLNB in appropriate patients.

Immediate breast reconstruction in locally advanced breast cancer: is it safe?

PURPOSE: Immediate breast reconstruction (IBR) following mastectomy remains controversial for locally advanced breast cancer over concerns regarding recurrence and complications which may delay adjuvant therapies. This study aimed to compare the oncologic outcomes and surgical safety of IBR following mastectomy with mastectomy alone (MA) for locally advanced breast cancer. METHODS: All patients treated at the Providence Breast Center between 2012 and 2017 for biopsy-proven locally advanced breast cancer, AJCC (8th edition) clinical stages (IIB-IIIC), were included. Primary outcomes were overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Secondary outcomes included recurrence rate, adjuvant therapy use, and reoperation. RESULTS: 267 patients (112 IBR, 155 MA) were included. On average, IBR patients were younger (48.82 years vs 61.42 years, P < 0.001). Median study follow-up was 50.7 months. OS was higher among IBR patients (86.6% vs 73.5%, P < 0.05). However, no significant differences were found in DSS (87.5% vs 84.5%, P = 0.34), DFS (79.5% vs 78.7%, P = 0.55), local recurrence (0% vs 1.9%, P = 0.194), adjuvant therapy use (95.5% vs 91.6%, P = 0.155), or reoperation (1.8% vs 1.3%, P = 0.559). CONCLUSION: IBR is a safe option for patients with locally advanced breast cancer and does not negatively impact survival, cancer recurrence rates, and use of adjuvant therapy.

Deep Learning Improves Speed and Accuracy of Prostate Gland Segmentations on Magnetic Resonance Imaging for Targeted Biopsy.

PURPOSE: Targeted biopsy improves prostate cancer diagnosis. Accurate prostate segmentation on magnetic resonance imaging (MRI) is critical for accurate biopsy. Manual gland segmentation is tedious and time-consuming. We sought to develop a deep learning model to rapidly and accurately segment the prostate on MRI and to implement it as part of routine magnetic resonance-ultrasound fusion biopsy in the clinic. MATERIALS AND METHODS: A total of 905 subjects underwent multiparametric MRI at 29 institutions, followed by magnetic resonance-ultrasound fusion biopsy at 1 institution. A urologic oncology expert segmented the prostate on axial T2-weighted MRI scans. We trained a deep learning model, ProGNet, on 805 cases. We retrospectively tested ProGNet on 100 independent internal and 56 external cases. We prospectively implemented ProGNet as part of the fusion biopsy procedure for 11 patients. We compared ProGNet performance to 2 deep learning networks (U-Net and holistically-nested edge detector) and radiology technicians. The Dice similarity coefficient (DSC) was used to measure overlap with expert segmentations. DSCs were compared using paired t-tests. RESULTS: ProGNet (DSC=0.92) outperformed U-Net (DSC=0.85, p <0.0001), holistically-nested edge detector (DSC=0.80, p <0.0001), and radiology technicians (DSC=0.89, p <0.0001) in the retrospective internal test set. In the prospective cohort, ProGNet (DSC=0.93) outperformed radiology technicians (DSC=0.90, p <0.0001). ProGNet took just 35 seconds per case (vs 10 minutes for radiology technicians) to yield a clinically utilizable segmentation file. CONCLUSIONS: This is the first study to employ a deep learning model for prostate gland segmentation for targeted biopsy in routine urological clinical practice, while reporting results and releasing the code online. Prospective and retrospective evaluations revealed increased speed and accuracy.

Are we producing general surgeons who are ready for community or rural practice?

Summary: General surgery remains a broad and unclearly defined specialty in small and medium-sized communities, where general surgeons perform more subspecialty and non-core procedures than their urban counterparts. It is unclear what specific procedures are being performed or whether today's residents are being trained to meet community needs. We surveyed the members of the British Columbia (BC) Surgical Society and found that only 3% of BC's surgeons believe today's graduates are "definitely prepared" for a broad-based community practice. We also identified several non-core procedures performed more frequently by general surgeons in small and medium-sized communities. General surgery residency is narrowing its focus despite the fact that community general surgeons are maintaining a broad-based practice. To meet the needs of smaller communities, residency programs need to address the discrepancies that exist between the emphasis within the current training structure and the practice of our community surgeons.

Introducing oncoplastic breast surgery in a community hospital.

Oncoplastic breast surgery (OPBS) has been shown to increase breast-conserving surgery with improved oncologic and cosmetic outcomes, but access to OPBS in Canada varies greatly. This article summarizes the impact of introducing OPBS in a community hospital. All breast oncology surgery cases performed before and after the introduction of OPBS by a single surgeon were reviewed. After implementing OPBS in our centre, breast conservation increased from 30% to 50%, and the positive margin rate decreased from 25% to 10%. The completion mastectomy rate was lower in patients who received OPBS, and this group had a slightly higher readmission rate for postoperative hematoma. This review suggests OPBS can be performed safely in the community setting with appropriate training and improve outcomes in breast surgery for patients in smaller centres.

Burnout and psychological distress amongst Australian healthcare workers during the COVID-19 pandemic.

OBJECTIVE: To examine psychological distress in healthcare workers (HCWs) during the COVID-19 pandemic in April-May 2020. METHODS: A cross-sectional survey examining demographic, employment and mental health characteristics of HCWs in a large metropolitan hospital in Australia. RESULTS: HCWs showed significant symptoms of moderate-severe level depression (21%), anxiety (20%) and posttraumatic stress disorder (PTSD; 29%), associated with burnout, prior psychiatric history, profession and resilience. CONCLUSION: Despite low levels of COVID contact, moderate to high levels of psychological distress were reported. Continued monitoring and support for HCWs' mental well-being is warranted as the COVID-19 pandemic develops.

Effect of wound protectors on surgical site infection in patients undergoing whipple procedure.

BACKGROUND: Conflicting data persists for use of wound protectors in pancreatoduodenectomy (PD) to prevent surgical site infection (SSI). We aimed to examine, at a multi-institutional level, the effect of wound protectors on superficial or deep SSI following elective open PD. METHODS: The American College of Surgeons National Surgical Quality Improvement Program pancreatectomy procedure targeted participant use file was queried from 2016 to 2018. Planned open PD procedures were extracted. Univariable, multivariable, and propensity score matched analyses were conducted. RESULTS: 11,562 patients undergoing PD were evaluated, 27% of which used wound protectors. Wound protectors decreased superficial or deep SSI risk in all patients (5.7% vs. 9.5%, P < 0.001), patients who have (6.6% vs. 12.2%, P < 0.001) and who did not have (4.6% vs. 6.5%, P = 0.011) a biliary stent. Propensity score matched analysis confirms such results (OR = 0.56, 95% CI: 0.46-0.69, P < 0.001 overall, OR = 0.66, 95% CI: 0.46-0.95, P = 0.03 without biliary stent, OR = 0.57, 95% CI: 0.44-0.73, P < 0.001 with biliary stent). CONCLUSIONS: Wound protectors reduce risk of superficial or deep SSI in patients undergoing PD, yet only a quarter of PD were associated with their use. This protective effect is seen whether patients have or have not had preoperative biliary stenting.

Development and Prospective Validation of a Risk Calculator That Predicts a Low Risk Cohort for Atypical Ductal Hyperplasia Upstaging to Malignancy: Evidence for a Watch and Wait Strategy of a High-Risk Lesion.

BACKGROUND: Guidelines recommend surgical excision of atypical ductal hyperplasia (ADH) due to the concern of undersampling a potential malignancy on core needle biopsy (CNB). The purpose of this study was to determine clinical, radiological and pathological variables associated with ADH upstaging to cancer and to develop a predictive risk calculator capable of identifying women who have a low oncological risk of upstaging. METHODS: A prospectively collected database from a tertiary breast referral center was analyzed for women diagnosed with ADH on CNB between January 2013 to December 2017 who underwent surgical excision. CNB and surgical pathology reports were examined to determine rate of upstaging. The association between clinical, radiological and pathological variables were evaluated using regression analysis to determine predictors of ADH upstaging to cancer. Significant variables (p ≤ 0.05) identified on univariate analysis were assigned a score of "1" and were included in the ADH upstaging risk calculator. RESULTS: A total of 1986 patients underwent surgery for a high-risk lesion. We identified 318 (16.0%) patients who had ADH identified on their CNB who underwent surgery-of which 290 were included in our study. The upstage rate was 24.8%. Five variables were associated with upstaging and included in our calculator: (1) lesion > 5 mm on ultrasound; (2) lesion > 5 mm on mammogram; (3) one or more "high-risk" lesion(s) on CNB; (4) pathological suspicion for cancer and; (5) incomplete removal of calcifications on CNB. Patients with a score of 0 had a 2% risk of being upstaged to cancer and were deemed low risk with 17.2% of patients falling within this category. CONCLUSIONS: Patients with ADH on CNB can be stratified into a low oncological cohort who have a 2% risk of being upstaged to carcinoma. In the future, these select patients may be counselled and potentially offered observation as an alternative to surgery.

Minimally invasive hepatectomy is associated with decreased morbidity and resource utilization in the elderly.

BACKGROUND: The aim of this study was to evaluate whether elderly patients undergoing elective hepatectomy experience increased morbidity/mortality and whether these outcomes could be mitigated by minimally invasive hepatectomy (MIH). METHODS: 15,612 patients from 2014 to 2017 were identified in the Hepatectomy Targeted Procedure Participant Use File of the American College of Surgeons National Surgical Quality Improvement Program. Multivariable logistic regression models were constructed to examine the effect of elderly status (age ≥ 75 years, N = 1769) on outcomes with a subgroup analysis of elderly only patients by open (OH) versus MIH (robotic, laparoscopic, and hybrid, N = 4044). Propensity score matching was conducted comparing the effect of MIH to OH in elderly patients to ensure that results are not the artifact of imbalance in baseline characteristics. RESULTS: Overall, elderly patients had increased risk for 30-day mortality, major morbidity, prolonged length of hospital stay, and discharge to destination other than home. In the elderly subgroup, MIH was associated with decreased major morbidity (OR 0.71, P = 0.031), invasive intervention (OR 0.61, P = 0.032), liver failure (OR 0.15, P = 0.011), bleeding (OR 0.46, P < 0.001), and prolonged length of stay (OR 0.46, P < 0.001). Propensity score-matched analyses successfully matched 4021 pairs of patients treated by MIH vs. OH, and logistic regression analyses on this matched sample found that MIH was associated with decreased major complications (OR 0.69, P = 0.023), liver failure (OR 0.14, P = 0.010), bile leak (OR 0.46, P = 0.009), bleeding requiring transfusion (OR 0.46, P < 0.001), prolonged length of stay (OR 0.46, P < 0.001), and discharge to destination other than home (OR 0.691, P = 0.035) compared to OH. CONCLUSION: MIH is associated with decreased risk of major morbidity, liver failure, bile leak, bleeding, prolonged length of stay, and discharge to destination other than home among elderly patients in this retrospective study. However, MIH in elderly patients does not protect against postoperative mortality.

Is rTMS effective for anxiety symptoms in major depressive disorder? An efficacy analysis comparing left-sided high-frequency, right-sided low-frequency, and sequential bilateral rTMS protocols.

BACKGROUND: Anxiety symptoms are common in major depressive disorder. Whilst therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression is well-established, minimal research has investigated rTMS's efficacy in treating anxiety symptoms in depression. METHODS: This study investigates the effectiveness of rTMS in treating anxiety symptoms in depression, specifically the relative efficacy of the three rTMS protocols commonly used in clinical practice: left-sided high-frequency, right-sided low-frequency and sequential bilateral rTMS. Antidepressant efficacy of each rTMS protocol is also investigated. Treatment data for 697 patients were pooled from three studies across five sites. Changes in Beck's Anxiety Inventory (BAI) and the Hamilton Depression Rating Scale over 4-week rTMS courses were analysed using latent growth curve modelling. RESULTS: All rTMS protocols were effective in treating anxiety symptoms (mean BAI reduction, 8.13 points; p < 0.001) and depressive symptoms. Near therapeutic equivalence was seen across the three protocols. Improvement in depressive severity positively correlated with improvement in anxiety. Both high- and low-baseline anxiety scores showed overall symptom reduction. CONCLUSIONS: This study addresses the clinical knowledge gap pertaining to rTMS's therapeutic efficacy in treating anxiety symptoms in depression and the relative efficacy of three commonly used stimulation protocols. Our findings suggest therapeutic equivalence across left-sided high-frequency, right-sided low-frequency, and sequential bilateral rTMS approaches.