Treatment and prognostic implications of strong PD-L1 expression in primary hepatic sarcomatoid carcinoma.

Primary hepatic sarcomatoid carcinoma (HSC) is an extremely rare and aggressive subtype of primary liver cancer. HSC has uncertain pathogenesis and dismal prognosis with overall survival of only 8.3 months. The molecular alterations of HSC are also not well understood. In this study, the authors describe a patient who presented with a large liver mass. The patient underwent complete surgical resection and histological examination demonstrated HSC, infiltrating the stomach. PD-L1 was strongly positive in the tumor cells. The patient was started on anti-PD-L1 immunotherapy postsurgery and is doing well 15 months after surgical resection. Tumor whole exome sequencing revealed genetic alterations in TP53, NF2 and MAGEC3 genes, indicating their potential role in tumor development.

Primary sarcomatoid cancer of the liver is a rare type of severe cancer that generally has a very poor prognosis. People diagnosed with primary sarcomatoid of the liver normally survive for only a few months. Surgery is not very effective in treating this type of cancer and recurrence is common even after complete removal. In this paper, the authors report a patient who presented to them with a large liver tumor. The patient underwent operation and the tumor was completely removed from the liver. Pathological testing of the tumor revealed it was severe primary sarcomatoid liver cancer. The patient was started on an immunotherapy treatment. The treatment enhanced the ability of the body's immune system to fight cancer. The patient is doing well 15 months after the operation, which might mean that this type of immunotherapy treatment after surgery helps prolong the life of people diagnosed with primary sarcomatoid cancer of the liver.

Tobacco use behavior among adults exposed to cumulative adverse childhood experiences: A systematic review and meta analysis.

BACKGROUND: Tobacco use remains one of the most used substances among adults globally and substantially impacts individuals and society. Adverse childhood experiences (ACEs) contribute to tobacco use. However, the association between cumulative ACEs and tobacco use behaviors (TUB) has not been established in the literature. In this review, we aimed to estimate the prevalence of ACEs among adult tobacco users and evaluated the relationship between cumulative ACEs and TUB. METHODS: We identified original articles published before October 2022 by searching PubMed, CINAHL, and Psych INFO databases. Inclusion criteria were: English language, adults and used instruments assessing for cumulative ACEs defined as four or more ACEs. RESULTS: Forty-two studies, totaling 674,087 participants; predominantly cohort and cross-sectional in study design (n = 33). Exposure to 4 ≥ ACEs was significantly associated with increasing the odds of current tobacco use (n = 35), ever or former tobacco use (n = 13), tobacco use initiation, (n = 3) nicotine dependence (n = 1), and ever using electronic cigarettes (n = 1). In the meta-analysis, as compared to those without ACEs, those with 4 ≥ ACEs were twice as likely to have ever used tobacco (OR = 2.16, 95 %CI:1.73-2.70) and approximately four times more likely to have used tobacco currently (OR = 3.73, 95 %CI:2.69-5.18). CONCLUSION: The cumulative ACEs exposure can increase the risk for TUB. However, the evidence is limited primarily to cigarette use. Ongoing research into the effects of cumulative ACEs on TUB is needed to integrate trauma-informed intervention in treating tobacco use and guide public health initiatives aimed to reduce the prevalence of ACEs and TUB among adults.

Infections in inflammatory bowel disease patients on immunomodulator and biologic therapy are not associated with high serum drug levels.

BACKGROUND: Inflammatory bowel disease (IBD) therapies now utilise higher doses of immunomodulatory and biologic therapies, predisposing patients to an increased risk of infections. AIMS: We aimed to determine whether infections were associated with high anti-tumour necrosis factor (TNF) drug levels in IBD and to quantify the risk and consequences of infections. METHODS: Two retrospective studies were performed, a descriptive cohort study and a matched case-control study. For the matched case-control study, cases of infection occurring on anti-TNF agents were matched in a 1:2 ratio to controls of anti-TNF treated patients without infections. RESULTS: In the descriptive study, 76 infections occurred in 60 patients, including 49 bacterial, 24 viral, four fungal and four parasitic. Of these, 61 (80.3%) were on biologics, 49 (64.5%) on immunomodulators and 11 (14.5%) on corticosteroids. Thirty-four (44.7%) were on combination therapy, 27 (35.5%) on biologic monotherapy and 15 (19.7%) on immunomodulator monotherapy. Median anti-TNF drug levels in infection cases were 3.9 µg/mL for infliximab and 6.0 µg/mL for adalimumab. In the case-control study, 32 cases of infection in 27 anti-TNF treated patients were matched with 64 anti-TNF treated controls without infections. Among infection cases, 59.5% were on combination therapy versus 40.6% on biologic monotherapy (P = 0.59). Median drug levels for cases and controls respectively were 3.9 µg/mL versus 5.5 µg/mL for infliximab (P = 0.72) and 6.0 µg/mL versus 9.9 µg/mL for adalimumab (P = 0.34). CONCLUSION: Infections in patients with IBD were common, and the risk was highest with combination therapy. Infections were not associated with high serum anti-TNF levels.

Development and validation of a model to predict acute kidney injury following high-dose methotrexate in patients with lymphoma.

STUDY OBJECTIVE: To develop and validate a model for predicting acute kidney injury (AKI) after high-dose methotrexate (HDMTX) exposure. DESIGN: Retrospective analysis. SETTING: Multisite integrated health system throughout Minnesota and Wisconsin. PATIENTS: Adult patients with lymphoma who received HDMTX as a 4-h infusion. MEASUREMENTS AND MAIN RESULTS: LASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort. CONCLUSION: This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

Implementing Differentiated and Integrated HIV Prevention Services for Adolescent Girls and Young Women: Experiences From Oral PrEP Rollout in Primary Care Services in South Africa.

PURPOSE: In South Africa, adolescent girls and young women (AGYW, aged 15-24 years) are disproportionately affected by human immunodeficiency viruses (HIV). Oral pre-exposure prophylaxis (PrEP) has been available in South Africa since 2016; however, there is limited evidence on oral PrEP implementation and integration in real-world settings, particularly among AGYW. Project PrEP is an implementation science project that sought to inform the introduction and integration of oral PrEP as part of combination HIV prevention and sexual and reproductive health services (SRH) in South Africa. The project focused on AGYW, as a priority population in need of HIV prevention. This paper presents strategies Project PrEP employed to increase oral PrEP and SRH service access and utilization. METHODS: We present strategies employed to increase oral PrEP and SRH services uptake. Using routine monitoring data, facility assessments, stakeholder engagement, training and progress reports, and observations, we share implementation lessons learned and describe how strategies can be adapted by HIV prevention programs in different contexts. RESULTS: Approximately 22, 000 people initiated on oral PrEP (December 2018-December 2021) across eight facilities and four mobile clinics. Two-thirds (67%) of initiated clients were AGYW. DISCUSSION: Lessons are to be learned from the introduction of oral PrEP as implementers prepare for the introduction of new PrEP methods. Stakeholders must be continuously engaged to ensure buy-in, and social mobilization and demand creation should be contextual, focused, and innovative. Continuous staff training is needed to reinforce knowledge, and AGYW service delivery models must be local context relevant.

Comparing the Integration of Syndromic versus Etiological Management of Sexually Transmitted Infections Into HIV Pre-Exposure Prophylaxis Services for Adolescent Girls and Young Women, in South Africa.

South Africa has a high incidence of human immunodeficiency virus and sexually transmitted infections (STIs), particularly among adolescent girls and young women. National and global guidelines recommend varied strategies for integrating STI and pre-exposure prophylaxis (PrEP) services. PURPOSE: This paper describes the implementation of a syndromic compared to an etiological approach to STI integration within PrEP services in South Africa. METHODS: We analysed program data from eight fixed and four mobile clinics to describe a cascade of STI care and integration of syndromic management among clients accessing PrEP services. Diagnostic testing was conducted in a subset of clients to determine the prevalence of STIs and estimate the burden of disease missed using a syndromic approach. RESULTS: Between December 2018 and December 2021, 22,505 clients sought services and a high proportion (92.9%) was screened for STI symptoms. Of these, 9% of females and 3% of males had symptoms and 89.5% had recorded treatment. In a subset of PrEP clients (406 females, 70 males) screened through laboratory testing, chlamydia was identified in 25.7% of female and 20.0% of male samples, gonorrhea in 14.1% of female and 18.6% of male samples, and syphilis in 2.3% of female and 1.4% of male samples. Highest prevalence was found among females aged 18-20 years. DISCUSSION: Syndromic STI screening and management can be integrated into routine PrEP service delivery and can identify symptomatic STIs, but misses asymptomatic infections. PrEP clients have a high prevalence of treatable STIs. Etiologic approaches can identify more infections than syndromic screening, but cheap point-of-care tests are needed.

Bilateral giant emphysematous bullae complicate severe bronchial asthma in a young patient: case report.

Giant bullous emphysema is a progressive bullous disease that affects young male smokers. Bullae are unilateral and mostly present in the apical lobes. Inflammatory diseases are less common cause of underlying emphysematous deterioration of the lung than tobacco smoking or genetic conditions such as Alpha-1 antitrypsin deficiency. The current instance, however, is relatively rare because it involved a nonsmoking 14-year-old boy who was diagnosed with asthma for 8 years, and he was taking bronchodilators inhalers during acute exacerbation of asthma; he presented to the tertiary health facility with on-and-off episodes of difficulties in breathing and chest tightness for 2 weeks despite being on maximal therapy for his asthma. He was diagnosed with bilateral large emphysematous bullae by high-resolution computed tomography scan, where staged bilateral bullectomy was performed. Thoracotomy-based bullae excision is still a feasible option for improving pulmonary function and the overall quality of life of patients with giant bullae emphysema in resource-limited settings.

EPAC1 inhibition protects the heart from doxorubicin-induced toxicity.

Anthracyclines, such as doxorubicin (Dox), are widely used chemotherapeutic agents for the treatment of solid tumors and hematologic malignancies. However, they frequently induce cardiotoxicity leading to dilated cardiomyopathy and heart failure. This study sought to investigate the role of the exchange protein directly activated by cAMP (EPAC) in Dox-induced cardiotoxicity and the potential cardioprotective effects of EPAC inhibition. We show that Dox induces DNA damage and cardiomyocyte cell death with apoptotic features. Dox also led to an increase in both cAMP concentration and EPAC1 activity. The pharmacological inhibition of EPAC1 (with CE3F4) but not EPAC2 alleviated the whole Dox-induced pattern of alterations. When administered in vivo, Dox-treated WT mice developed a dilated cardiomyopathy which was totally prevented in EPAC1 knock-out (KO) mice. Moreover, EPAC1 inhibition potentiated Dox-induced cell death in several human cancer cell lines. Thus, EPAC1 inhibition appears as a potential therapeutic strategy to limit Dox-induced cardiomyopathy without interfering with its antitumoral activity.

Dexamethasone and persistent wound pain: a prespecified analysis of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial.

BACKGROUND: Dexamethasone is commonly administered intraoperatively to prevent postoperative nausea and vomiting and is believed to have analgesic properties. It is unknown whether it has an impact on chronic wound pain. METHODS: In this prespecified embedded superiority substudy of the randomised PADDI trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and were followed up for 6 months postoperatively. The primary outcome was the incidence of pain in the surgical wound at 6 months. Secondary outcomes included acute postoperative pain and correlates of chronic postsurgical pain. RESULTS: We included 8478 participants in the modified intention-to-treat population (4258 in the dexamethasone group and 4220 in the matched placebo group). The primary outcome occurred in 491 subjects (11.5%) in the dexamethasone arm and 404 (9.6%) subjects in the placebo arm (relative risk 1.2, 95% confidence interval 1.06-1.41, P=0.003). Maximum pain scores at rest and on movement in the first 3 postoperative days were lower in the dexamethasone group compared with the control group {median 5 (inter-quartile range [IQR] 3.0-8.0) vs 6 (IQR 3.0-8.0) and median 7 (IQR 5.0-9.0) vs 8 (IQR 6.0-9.0), P<0.001 for both}. Severity of postoperative pain was not predictive of chronic postsurgical pain. The severity of chronic postsurgical pain and the frequency of neuropathic features did not differ between treatment groups. CONCLUSION: Administration of dexamethasone 8 mg i.v. was associated with an increase in the risk of pain in the surgical wound 6 months after surgery. CLINICAL TRIAL REGISTRATION: ACTRN12614001226695.

Significance of nucleologenesis, ribogenesis, and nucleolar proteome in the pathogenesis and recurrence of hepatocellular carcinoma.

INTRODUCTION: Emerging evidence suggests that enhanced ribosome biogenesis, increased size, and quantitative distribution of nucleoli are associated with dysregulated transcription, which in turn drives a cell into aberrant cellular proliferation and malignancy. Nucleolar alterations have been considered a prognostic histological marker for aggressive tumors. More recently, advancements in the understanding of chromatin network (nucleoplasm viscosity) regulated liquid-liquid phase separation mechanism of nucleolus formation and their multifunctional role shed light on other regulatory processes, apart from ribosomal biogenesis of the nucleolus. AREAS COVERED: Using hepatocellular carcinoma as a model to study the role of nucleoli in tumor progression, we review the potential of nucleolus coalescence in the onset and development of tumors through non-ribosomal biogenesis pathways, thereby providing new avenues for early diagnosis and cancer therapy. EXPERT OPINION: Molecular-based classifications have failed to identify the nucleolar-based molecular targets that facilitate cell-cycle progression. However, the algorithm-based tumor risk identification with high-resolution medical images suggests prominent nucleoli, karyotheca, and increased nucleus/cytoplasm ratio as largely associated with tumor recurrence. Nonetheless, the role of the non-ribosomal functions of nucleoli in tumorigenesis remains elusive. This clearly indicates the lacunae in the study of the nucleolar proteins pertaining to cancer. [Figure: see text].

Biphenotypic Immunohistochemical Features and NTRK1 Amplification in Intermediate Cell Carcinoma of the Liver.

Intermediate cell carcinoma is one of the rarest forms of primary liver cancer comprising relatively monomorphic populations of neoplastic epithelial cells demonstrating simultaneous positivity of both hepatocyte and cholangiocyte immunohistochemical markers. Here in, we describe an adult male patient who underwent left hepatectomy for a large liver tumor. The pathological and immunohistochemical analysis revealed the malignant primary liver cancer with intermediate cell morphology and mixed immunophenotypic features consistent with intermediate cell carcinoma. Furthermore, the genomic profiling using the Next-generation sequencing (NGS) platform demonstrated that there is a novel amplification with copy number gain 12 (12 gene copies) in the Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1) gene, being an oncogenic driver of intermediate cell carcinoma. This is the first case report with the amplification in NTRK1 and emphasizes the importance of molecular oncology.

Dexamethasone and clinically significant postoperative nausea and vomiting: a prespecified substudy of the randomised perioperative administration of dexamethasone and infection (PADDI) trial.

BACKGROUND: Clinically significant postoperative nausea and vomiting (PONV) is a patient-reported outcome which reflects patient experience. Although dexamethasone prevents PONV, it is unknown what impact it has on this experience. METHODS: In this prespecified embedded superiority substudy of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and completed a validated PONV questionnaire. The primary outcome was the incidence of clinically significant PONV on day 1 or day 2 postoperatively. Secondary outcomes included the incidence of clinically significant PONV and severe PONV on days 1 and 2 considered separately. RESULTS: A total of 1466 participants were included, with 733 patients allocated to the dexamethasone arm and 733 to matched placebo. The primary outcome occurred in 52 patients (7.1%) in the dexamethasone arm and 66 (9%) patients in the placebo arm (relative risk [RR]=0.79; 95% confidence interval [CI], 0.56-1.11; P=0.18). Severe PONV occurred on day 2 in 27 patients (3.9%) in the dexamethasone arm and 47 patients (6.7%) in the placebo arm (RR=0.58; 95% CI, 0.37-0.92; P=0.02; number needed-to-treat (NNT)=36.7; 95% CI, 20-202). In the entire cohort of 8880 PADDI patients, lower nausea scores, less frequent administration of antiemetics, and fewer vomiting events were recorded by patients in the dexamethasone arm up to day 2 after surgery. CONCLUSIONS: Administration of dexamethasone 8 mg i.v. did not influence clinically significant PONV. Dexamethasone administration did, however, decrease the incidence and severity of PONV, and was associated with less frequent administration of antiemetic agents. CLINICAL TRIAL REGISTRATION: ACTRN12614001226695.

Postoperative anaemia and patient-centred outcomes after major abdominal surgery: a retrospective cohort study.

BACKGROUND: Compared with anaemia before surgery, the underlying pathogenesis and implications of postoperative anaemia are largely unknown. METHODS: This retrospective cohort study analysed prospective data obtained from 2983 adult patients across 47 centres enrolled in a clinical trial evaluating restrictive and liberal intravenous fluids. The primary endpoint was persistent disability or death up to 90 days after surgery. Secondary endpoints included major septic complications, hospital stay, and patient quality of recovery using a 15-item quality of recovery (QoR-15) score, hospital re-admissions, and disability-free survival up to 12 months after surgery. Anaemia and disability were defined according to the WHO definitions. Multivariable regression was used to adjust for baseline risk and surgery. RESULTS: A total of 2983 patients met inclusion criteria for this study, of which 78.5% (95% confidence interval [CI], 76.7-80.1%) had postoperative anaemia. Patients with postoperative anaemia had a higher adjusted risk of death or disability up to 90 days after surgery when compared with those without anaemia: 18.2% vs 9.2% (risk ratio [RR]=1.51; 95% CI, 1.10-2.07, P=0.011); lower QoR-15 scores on Day 3 and Day 30, 105 (95% CI, 87-119) vs 114 (95% CI, 99-128; P<0.001), and 130 (95% CI, 112-140) vs 139 (95% CI, 121-144; P<0.011), respectively; higher adjusted risk of a composite of mortality/septic complications, 2.01 (95% CI, 1.55-42.67; P<0.001); unplanned admission to ICU (RR=2.65; 95% CI, 1.65-4.23; P<0.001); and longer median (inter-quartile range [IQR]) hospital stays, 6.6 (4.4-12.4) vs 3.7 (2.5-6.5) days (P<0.001). CONCLUSIONS: Postoperative anaemia is common and is independently associated with poor outcomes after surgery. Optimal prevention and treatment strategies need to be investigated. CLINICAL TRIAL REGISTRATION: NCT04978285 (ClinicalTrials.gov).

Inclusion, characteristics, and outcomes of male and female participants in large international perioperative studies.

BACKGROUND: We compared baseline characteristics and outcomes and evaluated the subgroup effects of randomised interventions by sex in males and females in large international perioperative trials. METHODS: Nine randomised trials and two cohort studies recruiting adult patients, conducted between 1995 and 2020, were included. Baseline characteristics and outcomes common to six or more studies were evaluated. Regression models included terms for sex, study, and an interaction between the two. Comparing outcomes without adjustment for baseline characteristics represents the 'total effect' of sex on the outcome. RESULTS: Of 54 626 participants, 58% were male and 42% were female. Females were less likely to have ASA physical status ≥3 (56% vs 64%), to smoke (15% vs 23%), have coronary artery disease (21% vs 32%), or undergo vascular surgery (10% vs 23%). The pooled incidence of death was 1.6% in females and 1.8% in males (risk ratio [RR] 0.92; 95% confidence interval [CI]: 0.81-1.05; P=0.20), of myocardial infarction was 4.2% vs 4.5% (RR 0.92; 95% CI: 0.81-1.03; P=0.10), of stroke was 0.5% vs 0.6% (RR 1.03; 95% CI: 0.79-1.35; P=0.81), and of surgical site infection was 8.6% vs 8.3% (RR 1.03; 95% CI: 0.79-1.35; P=0.70). Treatment effects of three interventions demonstrated statistically significant effect modification by sex. CONCLUSIONS: Females were in the minority in all included studies. They were healthier than males, but outcomes were comparable. Further research is needed to understand the reasons for this discrepancy. CLINICAL TRIAL REGISTRATION: International Registry of Meta-Research (UID: IRMR_000011; 5 January 2021).

Outcomes of non-cystic fibrosis-related bronchiectasis post-lung transplantation.

BACKGROUND: Lung transplantation is a recognised treatment for end-stage lung disease due to bronchiectasis. Non-cystic fibrosis (CF) bronchiectasis and CF are often combined into one cohort; however, outcomes for non-CF bronchiectasis patients vary between centres, and in comparison with those for CF. AIMS: To compare lung transplantation mortality and morbidity of bronchiectasis (non-CF) patients with those with CF and other indications. METHODS: Retrospective analysis of patients undergoing lung transplantation between 1 January 2008 and 31 December 2013. Time to and cause of lung allograft loss was censored on 1 April 2018. A case-note review was conducted on a subgroup of 78 patients, to analyse hospital admissions as a marker of morbidity. RESULTS: A total of 341 patients underwent lung transplantation; 22 (6%) had bronchiectasis compared with 69 (20%) with CF. The 5-year survival for the bronchiectasis group was 32%, compared with CF (69%), obstructive lung disease (OLD) (64%), pulmonary hypertension (62%) and ILD (55%) (P = 0.008). Lung allograft loss due to chronic lung allograft dysfunction with predominant infection was significantly higher in the bronchiectasis group at 2 years. The rate of acute admissions was 2.24 higher in the bronchiectasis group when compared with OLD (P = 0.01). Patients with bronchiectasis spent 45.81 days in hospital per person year after transplantation compared with 18.21 days for CF. CONCLUSIONS: Bronchiectasis patients in the present study had a lower 5-year survival and poorer outcomes in comparison with other indications including CF. Bronchiectasis should be considered a separate entity to CF in survival analysis.

Dexamethasone and Surgical-Site Infection.

BACKGROUND: The glucocorticoid dexamethasone prevents nausea and vomiting after surgery, but there is concern that it may increase the risk of surgical-site infection. METHODS: In this pragmatic, international, noninferiority trial, we randomly assigned 8880 adult patients who were undergoing nonurgent, noncardiac surgery of at least 2 hours' duration, with a skin incision length longer than 5 cm and a postoperative overnight hospital stay, to receive 8 mg of intravenous dexamethasone or matching placebo while under anesthesia. Randomization was stratified according to diabetes status and trial center. The primary outcome was surgical-site infection within 30 days after surgery. The prespecified noninferiority margin was 2.0 percentage points. RESULTS: A total of 8725 participants were included in the modified intention-to-treat population (4372 in the dexamethasone group and 4353 in the placebo group), of whom 13.2% (576 in the dexamethasone group and 572 in the placebo group) had diabetes mellitus. Of the 8678 patients included in the primary analysis, surgical-site infection occurred in 8.1% (354 of 4350 patients) assigned to dexamethasone and in 9.1% (394 of 4328) assigned to placebo (risk difference adjusted for diabetes status, -0.9 percentage points; 95.6% confidence interval [CI], -2.1 to 0.3; P<0.001 for noninferiority). The results for superficial, deep, and organ-space surgical-site infections and in patients with diabetes were similar to those of the primary analysis. Postoperative nausea and vomiting in the first 24 hours after surgery occurred in 42.2% of patients in the dexamethasone group and in 53.9% in the placebo group (risk ratio, 0.78; 95% CI, 0.75 to 0.82). Hyperglycemic events in patients without diabetes occurred in 22 of 3787 (0.6%) in the dexamethasone group and in 6 of 3776 (0.2%) in the placebo group. CONCLUSIONS: Dexamethasone was noninferior to placebo with respect to the incidence of surgical-site infection within 30 days after nonurgent, noncardiac surgery. (Funded by the Australian National Health and Medical Research Council and others; PADDI Australian New Zealand Clinical Trials Registry number, ACTRN12614001226695.).