Incidence and relative risk of delirium after major surgery for patients with pre-operative depression: a systematic review and meta-analysis.

BACKGROUND: Delirium is a common and potentially serious complication after major surgery. A previous history of depression is a known risk factor for experiencing delirium in patients admitted to the hospital, but the generalised risk has not been estimated in surgical patients. METHODS: We conducted a systematic review and meta-analysis of studies reporting the incidence or relative risk (or relative odds) of delirium in the immediate postoperative period for adults with pre-operative depression. We included studies that defined depression as either a formal pre-existing diagnosis or having clinically important depressive symptoms measured using a patient-reported instrument before surgery. Multilevel random effects meta-analyses were used to estimate the pooled incidences and pooled relative risks. We also conducted subgroup analyses by various study-level characteristics to identify important moderators of pooled estimates. RESULTS: Forty-two studies (n = 4,664,051) from five continents were included. The pooled incidence of postoperative delirium for patients with pre-operative depression was 29% (95%CI 17-43%, I2 = 99.0%), compared with 15% (95%CI 6-28%, I2 = 99.8%) in patients without pre-operative depression and 21% (95% CI 11-33%, I2 = 99.8%) in the cohorts overall. For patients with pre-operative depression, the risk of delirium was 1.91 times greater (95%CI 1.68-2.17, I2 = 42.0%) compared with patients without pre-operative depression. CONCLUSIONS: Patients with a previous diagnosis of depression or clinically important depressive symptoms before surgery have substantially greater risk of experiencing delirium after surgery. Clinicians and patients should be informed of these increased risks. Robust screening and other risk mitigation strategies for postoperative delirium are warranted, especially for patients with pre-operative depression.

Apocynin Prevents Cigarette Smoke-Induced Anxiety-Like Behavior and Preserves Microglial Profiles in Male Mice.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and is primarily caused by cigarette smoking (CS). Neurocognitive comorbidities such as anxiety and cognitive impairments are common among people with COPD. CS-induced lung inflammation and oxidative stress may "spill-over" into the systemic circulation, driving the onset of these comorbidities. We investigated whether a prophylactic treatment with the NADPH Oxidase 2 (NOX2) inhibitor, apocynin, could prevent CS-induced neurocognitive impairments. Adult male BALB/c mice were exposed to CS (9 cigarettes/day, 5 days/week) or room air (sham) for 8 weeks with co-administration of apocynin (5 mg/kg, intraperitoneal injection once daily) or vehicle (0.01% DMSO in saline). Following 7 weeks of CS exposure, mice underwent behavioral testing to assess recognition and spatial memory (novel object recognition and Y maze, respectively) and anxiety-like behaviors (open field and elevated plus maze). Mice were then euthanized, and blood, lungs, and brains were collected. Apocynin partially improved CS-induced lung neutrophilia and reversed systemic inflammation (C-reactive protein) and oxidative stress (malondialdehyde). Apocynin exerted an anxiolytic effect in CS-exposed mice, which was associated with restored microglial profiles within the amygdala and hippocampus. Thus, targeting oxidative stress using apocynin can alleviate anxiety-like behaviors and could represent a novel strategy for managing COPD-related anxiety disorders.

Tumour microenvironment characterisation to stratify patients for hyperthermic intraperitoneal chemotherapy in high-grade serous ovarian cancer (OVHIPEC-1).

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with Stage III ovarian cancer following interval cytoreductive surgery (CRS). Optimising patient selection is essential to maximise treatment efficacy and avoid overtreatment. This study aimed to identify biomarkers that predict HIPEC benefit by analysing gene signatures and cellular composition of tumours from participants in the OVHIPEC-1 trial. METHODS: Whole-transcriptome RNA sequencing data were retrieved from high-grade serous ovarian cancer (HGSOC) samples from 147 patients obtained during interval CRS. We performed differential gene expression analysis and applied deconvolution methods to estimate cell-type proportions in bulk mRNA data, validated by histological assessment. We tested the interaction between treatment and potential predictors on progression-free survival using Cox proportional hazards models. RESULTS: While differential gene expression analysis did not yield any predictive biomarkers, the cellular composition, as characterised by deconvolution, indicated that the absence of macrophages and the presence of B cells in the tumour microenvironment are potential predictors of HIPEC benefit. The histological assessment confirmed the predictive value of macrophage absence. CONCLUSION: Immune cell composition, in particular macrophages absence, may predict response to HIPEC in HGSOC and these hypothesis-generating findings warrant further investigation. CLINICAL TRIAL REGISTRATION: NCT00426257.

Lessons learned from postmarketing withdrawals of expedited approvals for oncology drug indications.

In the past decade, there have been a record number of oncology therapy approvals by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Besides the EMA's conditional marketing authorisation programme and the FDA's Accelerated Approval Program, we observe a tendency towards fast approval for exploratory studies with non-randomised, uncontrolled designs and surrogate endpoints. This issue raises concerns about the robustness and effectiveness of accepted treatments, leaving patients and health-care professionals in a state of uncertainty. A substantial number of accelerated approvals have recently been withdrawn in the USA, with some still authorised in Europe, emphasising discrepancies in regulatory standards that affect both patients and society as a whole. We highlight examples of drugs, authorised on the basis of surrogate endpoints, that were later withdrawn due to an absence of overall survival benefit. Our findings address the challenges and consequences of accelerated approval pathways in oncology. In conclusion, this Policy Review calls for regulatory bodies to better align their procedures and insist on robust evidence, preferably through unbiased randomised controlled trials. Drug approval processes should prioritise patient benefit, overall survival, and quality of life to minimise risks and uncertainties for patients.

Differences in time to patient access to innovative cancer medicines in six European countries.

Patients across Europe face inequity regarding access to anticancer medicines. While access is typically evaluated through reimbursement status or sales data, patients can receive first access through early access programs (EAPs) or off-label use. This study aims to assess the time to patient access at the hospital level, considering different indications and countries. (Pre-)registered access to six innovative medicines (Olaparib, Niraparib, Ipilimumab, Osimeritinib, Nivolumab and Ibritunib) was measured using a cross-sectional survey. First patient access to medicines and indications were collected using the hospital databases. Nineteen hospitals from Hungary, Italy, the Netherlands, Belgium, Switzerland and France participated. Analysis showed that some hospitals achieved patient access before national reimbursement, primarily through EAPs. The average time from EMA-approval to patient access for these medicines was 2.1 years (Range: -0.9-7.1 years). Hospitals in Italy and France had faster access compared to Hungary and Belgium. Variation was also found within countries, with specialized hospitals (x̄: -0.9 years; SD: 2.0) more likely to provide patient access prior to national reimbursement than general hospitals (x̄: 0.4 years; SD: 2.9). Contextual differences were observed, with EAPs or off-label use being more prevalent in Switzerland than Hungary. Recent EMA-approved indications and drug combinations reached patients at a later stage. Substantial variation in patient access time was observed between and within countries. Improving pricing and reimbursement timelines, fostering collaboration between national health authorities and market authorization holders, and implementing nationally harmonized, data-generating EAPs can enhance timely and equitable patient access to innovative cancer treatments in Europe.

Ginsenosides enhance P2X7-dependent cytokine secretion from LPS-primed rodent macrophages.

The activation of P2X7 is a well-known stimulus for the NLRP3-caspase 1 inflammasome and subsequent rapid IL-1ß secretion from monocytes and macrophages. Here we show that positive allosteric modulators of P2X7, ginsenosides, can enhance the release of three important cytokines, IL-1ß, IL-6 and TNF-α from LPS-primed rodent macrophages using the J774 mouse macrophage cell line and primary rat peritoneal macrophages. We compared the immediate P2X7 responses in un-primed and LPS-primed macrophages and found no difference in calcium response amplitude or kinetics. These results suggest that under inflammatory conditions positive allosteric modulators are capable of increasing cytokine secretion at lower concentrations of ATP, thus boosting the initial pro-inflammatory signal. This may be important in the control of intracellular infections.

Targeting accelerated pulmonary ageing to treat chronic obstructive pulmonary disease-induced neuropathological comorbidities.

Chronic obstructive pulmonary disease (COPD) is a major incurable health burden, ranking as the third leading cause of death worldwide, mainly driven by cigarette smoking. COPD is characterised by persistent airway inflammation, lung function decline and premature ageing with the presence of pulmonary senescent cells. This review proposes that cellular senescence, a state of stable cell cycle arrest linked to ageing, induced by inflammation and oxidative stress in COPD, extends beyond the lungs and affects the systemic circulation. This pulmonary senescent profile will reach other organs via extracellular vesicles contributing to brain inflammation and damage, and increasing the risk of neurological comorbidities, such as stroke, cerebral small vessel disease and Alzheimer's disease. The review explores the role of cellular senescence in COPD-associated brain conditions and investigates the relationship between cellular senescence and circadian rhythm in COPD. Additionally, it discusses potential therapies, including senomorphic and senolytic treatments, as novel strategies to halt or improve the progression of COPD.

Intestinal dysbiosis as an intraoperative predictor of septic complications: evidence from human surgical cohorts and preclinical models of peritoneal sepsis.

Major surgery exposes the intestinal microbiota to inflammatory and antibiotic stressors, which alter the microbiota composition of the intestinal lumen and fecal contents. However, it is not sufficiently understood, if such dysbiosis develops already during surgery and if alterations in microbiota may be the cause of surgical complications. End-of-surgery composition of the microbiota in the rectum was assessed in 41 patients undergoing either rectal or duodenopancreatic resection and was compared to baseline before surgery using 16S-rRNA sequencing. A subset of patients developed severe dysbiosis at the end of surgery, which was characterized by an overgrowth of the Proteobacteria phylum that includes the facultative pathogen E. coli. To test if dysbiosis impacts on surgical outcomes, dysbiosis was modeled in mice by a single oral administration of vancomycin prior to cecal ligation and puncture. Dysbiosis was associated with impaired post-surgical survival, dysregulation of the host's immune response, elevated bacterial virulence and reduced bacterial metabolism of carbon sources. In conclusion, dysbiosis can be detected already at the end of surgery in a fraction of patients undergoing major surgery. Modelling surgery-associated dysbiosis in mice using single-shot administration of vancomycin induced dysbiosis and resulted in elevated mortality.

Reproductive Health Among Those with Schizophrenia Spectrum Disorders: An Overview of Considerations Related to the Premenopausal Period, Pregnancy and Postpartum, and the Menopausal Transition, with a Focus on Recent Findings.

PURPOSE OF REVIEW: Schizophrenia spectrum disorders (SSD) impact many aspects of reproductive health for women and non-binary and transgender individuals assigned female at birth. In this narrative review, we highlight considerations and recent research related to (1) the premenopausal period, (2) pregnancy and postpartum, and (3) the menopausal transition. RECENT FINDINGS: Most recent research has focused on pregnancy and the postpartum period, and specifically on elucidating perinatal risk factors, adverse obstetrical and neonatal outcomes (and modifiable contributors such as smoking), long-term child health, and psychotropic medications (with reassuring results related antipsychotic-associated gestational diabetes mellitus and neurodevelopmental outcomes). Much less recent focus has been on menstruation and menopause, although some research has highlighted the relative worsening of illness peri-menstrually and peri-menopausally. Despite the many important reproductive considerations for those with SSD, many aspects including menstruation and menopause have received very little attention. Further research is needed on how to best support women, non-binary, and transgender people assigned female at birth with SSD throughout the lifespan.

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial.

BACKGROUND: The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up. METHODS: In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18-76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0-2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed. FINDINGS: Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4-12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5-13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6-12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0-18·5]; hazard ratio [HR] 0·63 [95% CI 0·48-0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0-39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6-55·1]; HR 0·70 [95% CI 0·53-0·92], stratified log-rank p=0·011). INTERPRETATION: These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. FUNDING: Dutch Cancer Foundation (KWF Kankerbestrijding).

Access to symptom screening and severe symptom risk among cancer patients with major mental illness.

INTRODUCTION: Cancer symptom screening has the potential to improve cancer outcomes, including reducing symptom burden among patients with major mental illness (MMI). We determined rates of symptom screening with the Edmonton Symptom Assessment System (ESAS-r) and risk of severe symptoms in cancer patients with MMI. METHODS: This retrospective cohort study used linked administrative health databases of adults diagnosed with cancer between 2007 and 2020. An MMI was measured in the 5 years prior to cancer diagnosis and categorized as inpatient, outpatient, or no MMI. Outcomes were defined as time to first ESAS-r screening and time to first moderate-to-severe symptom score. Cause-specific and Fine and Gray competing events models were used for both outcomes, controlling for age, sex, rural residence, year of diagnosis and cancer site. RESULTS: Of 389,870 cancer patients, 4049 (1.0%) had an inpatient MMI and 9775 (2.5%) had an outpatient MMI. Individuals with inpatient MMI were least likely to complete an ESAS-r (67.5%) compared to those with outpatient MMI (72.3%) and without MMI (74.8%). Compared to those without MMI, individuals with an inpatient or outpatient MMI had a lower incidence of symptom screening records after accounting for the competing risk of death (subdistribution Hazard Ratio 0.77 (95% CI 0.74-0.80) and 0.88 (95% CI 0.86-0.90) respectively). Individuals with inpatient and outpatient MMI status consistently had a significantly higher risk of reporting high symptom scores across all symptoms. CONCLUSIONS: Understanding the disparity in ESAS-r screening and management for cancer patients with MMI is a vital step toward providing equitable cancer care.

Targeted combination therapies in oncology: Challenging regulatory frameworks designed for monotherapies in Europe.

The pharmaceutical value chain, including clinical trials, pricing, access, and reimbursement, is designed for classical monotherapies. Although there has been a paradigm shift that increases the relevance of targeted combination therapies (TCTs), regulation and common practice have been slow to adapt. We explored access to 23 TCTs for advanced melanoma and lung cancer as reported by 19 specialists from 17 leading cancer institutions in nine European countries. We find heterogeneous patient access to TCTs between countries, differences in country-specific regulations, and differences in the clinical practice of melanoma and lung cancer. Regulation that is better tailored to the context of combinational therapies can increase equity in access across Europe and promote an evidence-based and authorized use of combinations.

Mid-term proximal sealing zone evaluation after fenestrated endovascular aortic aneurysm repair.

BACKGROUND: Fenestrated endovascular aortic aneurysm repair (FEVAR) is used in pararenal abdominal aortic aneurysms to achieve a durable proximal seal. This study investigated the mid-term course of the proximal fenestrated stent graft (FSG) sealing zone on the first and latest available post-FEVAR computed tomographic angiography (CTA) scan in a single-center series. METHODS: In 61 elective FEVAR patients, the shortest length of circumferential apposition between the FSG and the aortic wall (shortest apposition length [SAL]) was retrospectively assessed on the first and last available postoperative CTA scans. Patient records were reviewed for FEVAR-related procedural details, complications, and reinterventions. RESULTS: The median (interquartile range) time between the FEVAR procedure and the first and last CTA scan was 35 (30-48) days and 2.6 (1.2-4.3) years, respectively. The median (interquartile range) SAL was 38 (29-48) mm, and 44 (34-59) mm on the first and last CTA scans, respectively. During follow-up, the SAL increased >5 mm in 32 patients (52%), and decreased >5 mm in six patients (10%). Reintervention was performed for a type 1a endoleak in one patient. Twelve other patients needed 17 reinterventions for other FEVAR-related complications. CONCLUSIONS: Good mid-term apposition of the FSG in the pararenal aorta was achieved post-FEVAR, and the occurrence of type 1a endoleaks was low. The number of reinterventions was substantial, however, but for reasons other than loss of proximal seal.

Inhibition of oxidative stress by apocynin attenuated chronic obstructive pulmonary disease progression and vascular injury by cigarette smoke exposure.

BACKGROUND AND PURPOSE: Cardiovascular disease affects up to half of the patients with chronic obstructive pulmonary disease (COPD), exerting deleterious impact on health outcomes and survivability. Vascular endothelial dysfunction marks the onset of cardiovascular disease. The present study examined the effect of a potent NADPH Oxidase (NOX) inhibitor and free-radical scavenger, apocynin, on COPD-related cardiovascular disease. EXPERIMENTAL APPROACH: Male BALB/c mice were exposed to either room air (Sham) or cigarette smoke (CS) generated from 9 cigarettes·day-1 , 5 days a week for up to 24 weeks with or without apocynin treatment (5 mg·kg-1 ·day-1 , intraperitoneal injection). KEY RESULTS: Eight-weeks of apocynin treatment reduced airway neutrophil infiltration (by 42%) and completely preserved endothelial function and endothelial nitric oxide synthase (eNOS) availability against the oxidative insults of cigarette smoke exposure. These preservative effects were maintained up until the 24-week time point. 24-week of apocynin treatment markedly reduced airway inflammation (reduced infiltration of macrophage, neutrophil and lymphocyte), lung function decline (hyperinflation) and prevented airway collagen deposition by cigarette smoke exposure. CONCLUSION AND IMPLICATIONS: Limiting NOX activity may slow COPD progression and lower cardiovascular disease risk, particularly when signs of oxidative stress become evident.

Cigarette smoke-induced pulmonary impairment is associated with social recognition memory impairments and alterations in microglial profiles within the suprachiasmatic nucleus of the hypothalamus.

Chronic obstructive pulmonary disease (COPD) is a major, incurable respiratory condition that is primarily caused by cigarette smoking (CS). Neurocognitive disorders including cognitive dysfunction, anxiety and depression are highly prevalent in people with COPD. It is understood that increased lung inflammation and oxidative stress from CS exposure may 'spill over' into the systemic circulation to promote the onset of these extra-pulmonary comorbidities, and thus impacts the quality of life of people with COPD. The precise role of the 'spill-over' of inflammation and oxidative stress in the onset of COPD-related neurocognitive disorders are unclear. The present study investigated the impact of chronic CS exposure on anxiety-like behaviors and social recognition memory, with a particular focus on the role of the 'spill-over' of inflammation and oxidative stress from the lungs. Adult male BALB/c mice were exposed to either room air (sham) or CS (9 cigarettes per day, 5 days a week) for 24 weeks and were either daily co-administered with the NOX2 inhibitor, apocynin (5 mg/kg, in 0.01 % DMSO diluted in saline, i.p.) or vehicle (0.01 % DMSO in saline) one hour before the initial CS exposure of the day. After 23 weeks, mice underwent behavioral testing and physiological diurnal rhythms were assessed by monitoring diurnal regulation profiles. Lungs were collected and assessed for hallmark features of COPD. Consistent with its anti-inflammatory and oxidative stress properties, apocynin treatment partially lessened lung inflammation and lung function decline in CS mice. CS-exposed mice displayed marked anxiety-like behavior and impairments in social recognition memory compared to sham mice, which was prevented by apocynin treatment. Apocynin was unable to restore the decreased Bmal1-positive cells, key in cells in diurnal regulation, in the suprachiasmatic nucleus of the hypothalamus to that of sham levels. CS-exposed mice treated with apocynin was associated with a restoration of microglial area per cell and basal serum corticosterone. This data suggests that we were able to model the CS-induced social recognition memory impairments seen in humans with COPD. The preventative effects of apocynin on memory impairments may be via a microglial dependent mechanism.

Additive energetic contributions of multiple peptide positions determine the relative promiscuity of viral and human sequences for PDZ domain targets.

Protein-protein interactions that involve recognition of short peptides are critical in cellular processes. Protein-peptide interaction surface areas are relatively small and shallow, and there are often overlapping specificities in families of peptide-binding domains. Therefore, dissecting selectivity determinants can be challenging. PDZ domains are a family of peptide-binding domains located in several intracellular signaling and trafficking pathways. These domains are also directly targeted by pathogens, and a hallmark of many oncogenic viral proteins is a PDZ-binding motif. However, amidst sequences that target PDZ domains, there is a wide spectrum in relative promiscuity. For example, the viral HPV16 E6 oncoprotein recognizes over double the number of PDZ domain-containing proteins as the cystic fibrosis transmembrane conductance regulator (CFTR) in the cell, despite similar PDZ targeting-sequences and identical motif residues. Here, we determine binding affinities for PDZ domains known to bind either HPV16 E6 alone or both CFTR and HPV16 E6, using peptides matching WT and hybrid sequences. We also use energy minimization to model PDZ-peptide complexes and use sequence analyses to investigate this difference. We find that while the majority of single mutations had marginal effects on overall affinity, the additive effect on the free energy of binding accurately describes the selectivity observed. Taken together, our results describe how complex and differing PDZ interactomes can be programmed in the cell.

Additive energetic contributions of multiple peptide positions determine the relative promiscuity of viral and human sequences for PDZ domain targets.

Protein-protein interactions that include recognition of short sequences of amino acids, or peptides, are critical in cellular processes. Protein-peptide interaction surface areas are relatively small and shallow, and there are often overlapping specificities in families of peptide-binding domains. Therefore, dissecting selectivity determinants can be challenging. PDZ domains are an example of a peptide-binding domain located in several intracellular signaling and trafficking pathways, which form interactions critical for the regulation of receptor endocytic trafficking, tight junction formation, organization of supramolecular complexes in neurons, and other biological systems. These domains are also directly targeted by pathogens, and a hallmark of many oncogenic viral proteins is a PDZ-binding motif. However, amidst sequences that target PDZ domains, there is a wide spectrum in relative promiscuity. For example, the viral HPV16 E6 oncoprotein recognizes over double the number of PDZ domain-containing proteins as the cystic fibrosis transmembrane conductance regulator (CFTR) in the cell, despite similar PDZ targeting-sequences and identical motif residues. Here, we determine binding affinities for PDZ domains known to bind either HPV16 E6 alone or both CFTR and HPV16 E6, using peptides matching WT and hybrid sequences. We also use energy minimization to model PDZ-peptide complexes and use sequence analyses to investigate this difference. We find that while the majority of single mutations had a marginal effect on overall affinity, the additive effect on the free energy of binding accurately describes the selectivity observed. Taken together, our results describe how complex and differing PDZ interactomes can be programmed in the cell.

No impact of sex on surgical site infections in abdominal surgery: a multi-center study.

OBJECTIVE: Male sex is controversially discussed as a risk factor for surgical site infections (SSI). The aim of the present study was to evaluate the impact of sex on SSI in abdominal surgery under elimination of relevant confounders. METHODS: Clinicopathological data of 6603 patients undergoing abdominal surgery from a multi-center prospective database of four Swiss hospitals including patients between 2015 and 2018 were assessed. Patients were stratified according to postoperative SSI and risk factors for SSI were identified using univariate and multivariate analysis. RESULTS: In 649 of 6603 patients, SSI was reported (9.8%). SSI was significantly associated with reoperation (22.7% vs. 3.4%, p < 0.001), increased mortality rate (4.6% vs. 0.9%, p < 0.001), and increased rate of length of hospital stay > 75th percentile (57.0% vs. 17.9%, p < 0.001). In univariate analysis, male sex was a significant risk factor for SSI (p = 0.01). In multivariate analysis including multiple confounders' such as comorbidities and perioperative factors, there was no association between male sex and risk of SSI (odds ratio (OR) 1.1 [CI 0.8-1.4]). Independent risk factors for SSI in multivariate analysis were BMI ≥ 30 kg/m2 (OR 1.8 [CI 1.3-2.3]), duration of surgery > 75th percentile (OR 2.3 [1.8-2.9]), high contamination level (OR 1.3 [1.0-1.6]), laparotomy (OR 1.3 [1.0-1.7]), previous laparotomy (OR 1.4 [1.1-1.7]), blood transfusion (OR 1.7 [1.2-2.4]), cancer (OR 1.3 [1.0-1.8] and malnutrition (OR 2.5 [1.8-3.4]). CONCLUSION: Under elimination of relevant confounders, there is no significant correlation between sex and risk of SSI after abdominal surgery.

Empyema after image-guided percutaneous intercostal drainage of subdiaphragmatic collection: a case series.

Background: Treatment of subdiaphragmatic collection by intercostal image-guided drain placement is associated with a risk of pleural complications including potentially life-threatening pleural empyema. Descriptions of patient characteristics and clinical course of postinterventional pleural empyema are lacking. We aim to present characteristics, clinical course and outcomes of patients with empyema after intercostal approach of drain placement. Methods: Data was collected as a retrospective single center case series and included adult patients with decortication for treatment of pleural empyema after image-guided percutaneous intercostal drainage of a subdiaphragmatic collection between 01.01.2009 and 31.01.2021. Results: We identified ten patients, nine male and one female, all suffering from subdiaphragmatic collection treated with intercostal drain. All patients developed pleural empyema after drain placement and received surgical decortication. Similarities between patients were drain placement under computed tomography (CT)-guidance (eight of ten patients), lateral position of the drain (seven of ten patients), drain insertion in the eighth intercostal space (ICS) (six of ten patients) and existing comorbidities as malnutrition (six of ten patients), diabetes (four of ten patients) and cancer (three of ten patients). The majority of patients had a prolonged length of hospital stay (LOS) with an average duration of 40 days. Nearly half of the patients needed intensive care unit (ICU) treatment and one patient died postoperatively from respiratory exhaustion. Conclusions: In this series, empyema after intercostal drainage was associated with prolonged LOS and was potentially life-threatening. The most commonly shared features in our cohort were the high prevalence of comorbidities, drain insertion above ninth ICS as well as lateral position of the drain. These factors should be addressed in prospective studies to evaluate potential correlation with postinterventional empyema. For optimal management of patients with subdiaphragmatic collection treated by intercostal drainage, awareness of potential associated complications is crucial.