Quantifying Posttraumatic Stress Disorder Symptoms During Traumatic Memories Using Interpretable Markers of Respiratory Variability.

BACKGROUND: Posttraumatic stress disorder (PTSD) causes heightened fight-or-flight responses to traumatic memories (i.e., hyperarousal). Although hyperarousal is hypothesized to cause irregular breathing (i.e., respiratory variability), no quantitative markers of respiratory variability have been shown to correspond with PTSD symptoms in humans. OBJECTIVE: In this study, we define interpretable markers of respiration pattern variability (RPV) and investigate whether these markers respond during traumatic memories, correlate with PTSD symptoms, and differ in patients with PTSD. METHODS: We recruited 156 veterans from the Vietnam-Era Twin Registry to participate in a trauma recall protocol. From respiratory effort and electrocardiogram measurements, we extracted respiratory timings and rate using a robust quality assessment and fusion approach. We then quantified RPV using the interquartile range and compared RPV between baseline and trauma recall conditions, correlated PTSD symptoms to the difference between trauma recall and baseline RPV (i.e., ∆RPV), and compared ∆RPV between patients with PTSD and trauma-exposed controls. Leveraging a subset of 116 paired twins, we then uniquely controlled for factors shared by co-twins via within-pair analysis for further validation. RESULTS: We found RPV was increased during traumatic memories (p .001), ∆ RPV was positively correlated with PTSD symptoms (p .05), and patients with PTSD exhibited higher ∆ RPV than trauma-exposed controls (p .05). CONCLUSIONS: This paper is the first to elucidate RPV markers that respond during traumatic memories, especially in patients with PTSD, and correlate with PTSD symptoms. SIGNIFICANCE: These findings encourage future studies outside the clinic, where interpretable markers of respiratory variability are used to track hyperarousal.

Venom-inspired somatostatin receptor 4 (SSTR4) agonists as new drug leads for peripheral pain conditions.

Persistent pain affects one in five people worldwide, often with severely debilitating consequences. Current treatment options, which can be effective for mild or acute pain, are ill-suited for moderate-to-severe persistent pain, resulting in an urgent need for new therapeutics. In recent years, the somatostatin receptor 4 (SSTR 4 ), which is expressed in sensory neurons of the peripheral nervous system, has emerged as a promising target for pain relief. However, the presence of several closely related receptors with similar ligand-binding surfaces complicates the design of receptor-specific agonists. In this study, we report the discovery of a potent and selective SSTR 4 peptide, consomatin Fj1, derived from extensive venom gene datasets from marine cone snails. Consomatin Fj1 is a mimetic of the endogenous hormone somatostatin and contains a minimized binding motif that provides stability and drives peptide selectivity. Peripheral administration of synthetic consomatin Fj1 provided analgesia in mouse models of postoperative and neuropathic pain. Using structure-activity studies, we designed and functionally evaluated several Fj1 analogs, resulting in compounds with improved potency and selectivity. Our findings present a novel avenue for addressing persistent pain through the design of venom-inspired SSTR 4 -selective pain therapeutics. One Sentence Summary: Venom peptides from predatory marine mollusks provide new leads for treating peripheral pain conditions through a non-opioid target.

Genome-Wide Investigation of Exogenous Female Hormones, Genetic Variation, and Venous Thromboembolism Risk.

BACKGROUND: Increased risk of venous thromboembolism (VTE) is a life-threatening side effect for users of oral contraceptives (OCs) or hormone therapy (HT). OBJECTIVES: To investigate the potential for genetic predisposition to VTE in OC or HT users, we conducted a gene-by-environment (GxE) case-only meta-analysis of genome-wide association studies (GWAS). METHODS: Use or non-use of OCs (7 studies) or HT (8 studies) at the time of the VTE event was determined by pharmacy records or self-report. A synergy index (SI) was modeled for each variant in each study and estimated supra-multiplicative GxE interaction. The SI parameters were first meta-analyzed across OC and HT studies, and subsequently meta-analyzed to obtain an overall estimate. The primary analysis was agnostic GWAS and interrogated all imputed genotypes using a p-value threshold of <5.0x10-8; secondary analyses were candidate-based. RESULTS: The VTE case-only OC meta-analysis included 2,895 OC users and 6,607 non-users; the case-only HT meta-analysis included 2,434 HT users and 12,793 non-users. In primary GWAS meta-analyses, no variant reached genome-wide significance, but the smallest p-value approached statistical significance: rs9386463 (p = 5.03x10-8). We tested associations for 138 candidate variants and identified 2 that exceeded statistical significance (0.05/138=3.62x10-4): F5 rs6025 (p = 1.87x10-5, SI = 1.29: previously observed) and F11 rs2036914 (p = 2.0x10-4, SI = 0.91; new observation). CONCLUSIONS: The candidate-variant approach to identify supra-multiplicative associations between genetic variation and OC-HT use identified a new association with common genetic variation in F11 while the agnostic interrogations did not yield new discoveries.

Key residues in the VDAC2-BAK complex can be targeted to modulate apoptosis.

BAK and BAX execute intrinsic apoptosis by permeabilising the mitochondrial outer membrane. Their activity is regulated through interactions with pro-survival BCL-2 family proteins and with non-BCL-2 proteins including the mitochondrial channel protein VDAC2. VDAC2 is important for bringing both BAK and BAX to mitochondria where they execute their apoptotic function. Despite this important function in apoptosis, while interactions with pro-survival family members are well characterised and have culminated in the development of drugs that target these interfaces to induce cancer cell apoptosis, the interaction between BAK and VDAC2 remains largely undefined. Deep scanning mutagenesis coupled with cysteine linkage identified key residues in the interaction between BAK and VDAC2. Obstructive labelling of specific residues in the BH3 domain or hydrophobic groove of BAK disrupted this interaction. Conversely, mutating specific residues in a cytosol-exposed region of VDAC2 stabilised the interaction with BAK and inhibited BAK apoptotic activity. Thus, this VDAC2-BAK interaction site can potentially be targeted to either inhibit BAK-mediated apoptosis in scenarios where excessive apoptosis contributes to disease or to promote BAK-mediated apoptosis for cancer therapy.

Scalable and efficient DNA sequencing analysis on different compute infrastructures aiding variant discovery.

DNA variation analysis has become indispensable in many aspects of modern biomedicine, most prominently in the comparison of normal and tumor samples. Thousands of samples are collected in local sequencing efforts and public databases requiring highly scalable, portable, and automated workflows for streamlined processing. Here, we present nf-core/sarek 3, a well-established, comprehensive variant calling and annotation pipeline for germline and somatic samples. It is suitable for any genome with a known reference. We present a full rewrite of the original pipeline showing a significant reduction of storage requirements by using the CRAM format and runtime by increasing intra-sample parallelization. Both are leading to a 70% cost reduction in commercial clouds enabling users to do large-scale and cross-platform data analysis while keeping costs and CO2 emissions low. The code is available at https://nf-co.re/sarek.

Imaging vs Nonimaging Raman Spectroscopy for High-Throughput Single-Cell Phenotyping.

Raman spectroscopy can provide nonbiased single-cell analysis based on the endogenous ensemble of biomolecules, with alterations in cellular content indicative of cell state and disease. The measurements themselves can be performed in a variety of modes: generally, full imaging takes the most time but can provide the most information. By reducing the imaging resolution and generating the most characteristic single-cell Raman spectrum in the shortest time, we optimize the utility of the Raman measurement for cell phenotyping. Here, we establish methods to compare these different measurement approaches and assess what, if any, undesired effects occur in the cell. Assuming that laser-induced damage should be apparent as a change in molecular spectra across sequential measurements, and by defining the information content as the Raman-based separability of two cell lines, we thereby establish a parameter range for optimum measurement sensitivity and single-cell throughput in single-cell Raman spectroscopic analysis. While the work here uses 532 nm irradiation, the same approach can be generalized to Raman analysis at other wavelengths.

Diagnostic impacts on management of soft tissue injuries associated with tibial plateau fractures: A narrative review.

INTRODUCTION: Currently there is no consensus on the need for investigating knee ligamentous and meniscal injuries in a patient with a tibial plateau fracture. Consequently, many soft tissue injuries are likely undiagnosed and therefore untreated. The impact this has on long term knee outcomes is not well defined. We aimed to identify the impacts of various diagnostic methods on the management of meniscal injuries associated with tibial plateau fractures and evaluate the clinical outcomes. MATERIALS AND METHODS: We performed a systematic review using Pubmed, Medline, Embase, CINAHL and Cochrane following Cochrane guidelines. We included studies that operatively managed tibial plateau fractures and soft tissue injuries, which were diagnosed with either preoperative MRI, intra-operative arthroscopy or arthrotomy. RESULTS: 18 articles with 884 people, with a mean age of 46.4 years were included. Soft tissue injuries were detected on MRI (32-73%) and arthroscopy (12-70%), of which the most common were lateral meniscal injuries (7-64% of tibial plateau fractures). When identified by arthroscopy and arthrotomy, these injuries were almost always treated, either by repair or debridement. The clinical outcomes of these patients were poorly reported, with a heterogenous use of patient reported outcome measures, and follow up time points. There were no randomised trials or control groups for comparative analysis, however operative treatment yielded good to excellent outcomes. CONCLUSION: There is a high incidence of concomitant soft tissue injuries with tibial plateau fractures, particularly lateral meniscal injuries. There are 2 main approaches to meniscal injuries: surgeons who don't investigate, don't treat, whilst surgeons who do investigate often do surgically treat. Although studies that treated these injuries achieved good to excellent results, the currently available evidence doesn't confirm treatment superiority. As there is plausibility for better outcomes, randomised studies are needed to further investigate this clinical question.

Deployment-related Cigarette Smoking Behaviors and Pulmonary Function Among U.S. Veterans.

INTRODUCTION: The effects of smoking on lung function among post-9/11 Veterans deployed to environments with high levels of ambient particulate matter are incompletely understood. MATERIALS AND METHODS: We analyzed interim data (04/2018-03/2020) from the Veterans Affairs (VA) Cooperative Studies Program #595, "Service and Health Among Deployed Veterans". Veterans with ≥1 land-based deployments enrolled at 1 of 6 regional Veterans Affairs sites completed questionnaires and spirometry. Multivariable linear regression models assessed associations between cigarette smoking (cumulative, deployment-related and non-deployment-related) with pulmonary function. RESULTS: Among 1,836 participants (mean age 40.7 ± 9.6, 88.6% male), 44.8% (n = 822) were ever-smokers (mean age 39.5 ± 9.5; 91.2% male). Among ever-smokers, 86% (n = 710) initiated smoking before deployment, while 11% (n = 90) initiated smoking during deployment(s). Smoking intensity was 50% greater during deployment than other periods (0.75 versus 0.50 packs-per-day; P < .05), and those with multiple deployments (40.4%) were more likely to smoke during deployment relative to those with single deployments (82% versus 74%). Total cumulative pack-years (median [IQR] = 3.8 [1, 10]) was inversely associated with post-bronchodilator FEV1%-predicted (-0.82; [95% CI] = [-1.25, -0.50] %-predicted per 4 pack-years) and FEV1/FVC%-predicted (-0.54; [95% CI] = [-0.78, -0.43] %-predicted per 4 pack-years). Deployment-related pack-years demonstrated similar point estimates of associations with FEV1%-predicted (-0.61; [95% CI] = [-2.28, 1.09]) and FEV1/FVC%-predicted (-1.09; [95% CI] = [-2.52, 0.50]) as non-deployment-related pack-years (-0.83; [95% CI] = [-1.26, -0.50] for FEV1%-predicted; -0.52; [95% CI] = [-0.73, -0.36] for FEV1/FVC%-predicted). CONCLUSIONS: Although cumulative pack-years smoking was modest in this cohort, an inverse association with pulmonary function was detectable. Deployment-related pack-years had a similar association with pulmonary function compared to non-deployment-related pack-years.

Viral genome sequencing to decipher in-hospital SARS-CoV-2 transmission events.

The SARS-CoV-2 pandemic has highlighted the need to better define in-hospital transmissions, a need that extends to all other common infectious diseases encountered in clinical settings. To evaluate how whole viral genome sequencing can contribute to deciphering nosocomial SARS-CoV-2 transmission 926 SARS-CoV-2 viral genomes from 622 staff members and patients were collected between February 2020 and January 2021 at a university hospital in Munich, Germany, and analysed along with the place of work, duration of hospital stay, and ward transfers. Bioinformatically defined transmission clusters inferred from viral genome sequencing were compared to those inferred from interview-based contact tracing. An additional dataset collected at the same time at another university hospital in the same city was used to account for multiple independent introductions. Clustering analysis of 619 viral genomes generated 19 clusters ranging from 3 to 31 individuals. Sequencing-based transmission clusters showed little overlap with those based on contact tracing data. The viral genomes were significantly more closely related to each other than comparable genomes collected simultaneously at other hospitals in the same city (n = 829), suggesting nosocomial transmission. Longitudinal sampling from individual patients suggested possible cross-infection events during the hospital stay in 19.2% of individuals (14 of 73 individuals). Clustering analysis of SARS-CoV-2 whole genome sequences can reveal cryptic transmission events missed by classical, interview-based contact tracing, helping to decipher in-hospital transmissions. These results, in line with other studies, advocate for viral genome sequencing as a pathogen transmission surveillance tool in hospitals.

A parabrachial hub for the prioritization of survival behavior.

Long-term sustained pain in the absence of acute physical injury is a prominent feature of chronic pain conditions. While neurons responding to noxious stimuli have been identified, understanding the signals that persist without ongoing painful stimuli remains a challenge. Using an ethological approach based on the prioritization of adaptive survival behaviors, we determined that neuropeptide Y (NPY) signaling from multiple sources converges on parabrachial neurons expressing the NPY Y1 receptor to reduce sustained pain responses. Neural activity recordings and computational modeling demonstrate that activity in Y1R parabrachial neurons is elevated following injury, predicts functional coping behavior, and is inhibited by competing survival needs. Taken together, our findings suggest that parabrachial Y1 receptor-expressing neurons are a critical hub for endogenous analgesic pathways that suppress sustained pain states.

Diagnostic utility of exome sequencing followed by research reanalysis in human brain malformations.

This study aimed to determine the diagnostic yield of singleton exome sequencing and subsequent research-based trio exome analysis in children with a spectrum of brain malformations seen commonly in clinical practice. We recruited children ≤ 18 years old with a brain malformation diagnosed by magnetic resonance imaging and consistent with an established list of known genetic causes. Patients were ascertained nationally from eight tertiary paediatric centres as part of the Australian Genomics Brain Malformation Flagship. Chromosome microarray was required for all children, and those with pathogenic copy number changes were excluded. Cytomegalovirus polymerase chain reaction on neonatal blood spots was performed on all children with polymicrogyria with positive patients excluded. Singleton exome sequencing was performed through a diagnostic laboratory and analysed using a clinical exome sequencing pipeline. Undiagnosed patients were followed up in a research setting, including reanalysis of the singleton exome data and subsequent trio exome sequencing. A total of 102 children were recruited. Ten malformation subtypes were identified with the commonest being polymicrogyria (36%), pontocerebellar hypoplasia (14%), periventricular nodular heterotopia (11%), tubulinopathy (10%), lissencephaly (10%) and cortical dysplasia (9%). The overall diagnostic yield for the clinical singleton exome sequencing was 36%, which increased to 43% after research follow-up. The main source of increased diagnostic yield was the reanalysis of the singleton exome data to include newly discovered gene-disease associations. One additional diagnosis was made by trio exome sequencing. The highest phenotype-based diagnostic yields were for cobblestone malformation, tubulinopathy and lissencephaly and the lowest for cortical dysplasia and polymicrogyria. Pathogenic variants were identified in 32 genes, with variants in 6/32 genes occurring in more than one patient. The most frequent genetic diagnosis was pathogenic variants in TUBA1A. This study shows that over 40% of patients with common brain malformations have a genetic aetiology identified by exome sequencing. Periodic reanalysis of exome data to include newly identified genes was of greater value in increasing diagnostic yield than the expansion to trio exome. This study highlights the genetic and phenotypic heterogeneity of brain malformations, the importance of a multidisciplinary approach to diagnosis and the large number of patients that remain without a genetic diagnosis despite clinical exome sequencing and research reanalysis.

The queen bee phenomenon in Canadian surgical subspecialties: An evaluation of gender biases in the resident training environment.

BACKGROUND: The queen bee phenomenon (QBP) describes the behavioural response that occurs when women achieve success in a male-dominated environment, and in this position of authority, treat their female subordinates more critically. It has been demonstrated in business, academia, the military, and police force. The goal of this study was to determine whether the QBP occurs in surgical specialties. We hypothesized that female surgeons, fellows, and senior surgical residents would be more critical in their assessment of junior female residents than their male counterparts. METHODS: A scenario-based survey was distributed via email to all Canadian surgical programs between February and March 2021. Scenarios were designed to assess either female or male learners. Centers distributed surveys to attending surgeons, surgical fellows, resident physicians, and affiliate surgeons. Respondents average Likert score for female-based and male-based questions were calculated. Subgroup analyses were performed based on gender, age, seniority, and surgical specialty. RESULTS: 716 survey responses were collected, with 387 respondents identifying as male (54%) and 321 identifying as female (45%). 385 attending surgeons (54%), 66 fellows (9%), and 263 residents (37%) responded. The mean Likert scores for female respondents assessing female learners was significantly lower than male learners (p = 0·008, CI = 95%). During subgroup analysis, some specialties demonstrated significant scoring differences. DISCUSSION: The QBP was shown to be present among surgical specialties. Female respondents assessed female learners more critically than their male counterparts. CONCLUSION: These findings highlight the importance of tackling organizational biases to create more equitable educational and work environment in surgery.

Comprehensive stability analysis of 13 ß-lactams and ß-lactamase inhibitors in in vitro media, and novel supplement dosing strategy to mitigate thermal drug degradation.

Non-clinical antibiotic development relies on in vitro susceptibility and infection model studies. Validating the achievement of the targeted drug concentrations is essential to avoid under-estimation of drug effects and over-estimation of resistance emergence. While certain ß-lactams (e.g., imipenem) and ß-lactamase inhibitors (BLIs; clavulanic acid) are believed to be relatively unstable, limited tangible data on their stability in commonly used in vitro media are known. We aimed to determine the thermal stability of 10 ß-lactams and 3 BLIs via LC-MS/MS in cation-adjusted Mueller Hinton broth at 25 and 36°C as well as agar at 4 and 37°C, and in water at -20, 4, and 25°C. Supplement dosing algorithms were developed to achieve broth concentrations close to their target over 24 h. During incubation in broth (pH 7.25)/agar, degradation half-lives were 16.9/21.8 h for imipenem, 20.7/31.6 h for biapenem, 29.0 h for clavulanic acid (studied in broth only), 23.1/71.6 h for cefsulodin, 40.6/57.9 h for doripenem, 46.5/64.6 h for meropenem, 50.8/97.7 h for cefepime, 61.5/99.5 h for piperacillin, and >120 h for all other compounds. Broth stability decreased at higher pH. All drugs were ≥90% stable for 72 h in agar at 4°C. Degradation half-lives in water at 25°C were >200 h for all drugs except imipenem (14.7 h, at 1,000 mg/L) and doripenem (59.5 h). One imipenem supplement dose allowed concentrations to stay within ±31% of their target concentration. This study provides comprehensive stability data on ß-lactams and BLIs in relevant in vitro media using LC-MS/MS. Future studies are warranted applying these data to antimicrobial susceptibility testing and assessing the impact of ß-lactamase-related degradation.

Calculations of the effect of catalyst size and structure on the electrocatalytic reduction of CO2 on Cu nanoclusters.

The structure and catalytic properties of Cu nanoclusters of sizes between 55 and 147 atoms were examined to understand if small Cu clusters could provide enhancement over traditional catalysts for the electrocatalysis of CO2 to CO and carbon-based fuels, such as CH4 and CH3OH, compared to bulk Cu surfaces and large Cu nanoparticles. Clusters studied included Cu55, Cu78, Cu101, Cu124, and Cu147, the structures of which were determined using global optimisation. The majority of Cu clusters examined were icosahedral, including the perfect closed-shell, partial-shell, elongated and distorted icosahedral clusters. Free energy diagrams for the reduction of CO2 showed the potential required for the formation of CO is notably smaller for all cluster sizes considered, relative to Cu(111). Less variation is observed for the limiting potential for the formation of CH4 and CH3OH. However, it was found that clusters that are either a distorted motif or contain vacancy defects yielded the best activity and provide an interesting synthesis target for future experiments.

Next generation antibiotic combinations to combat pan-drug resistant Klebsiella pneumoniae.

Antimicrobial resistance has emerged as one of the leading public health threats of the twenty-first century. Gram-negative pathogens have been a major contributor to the declining efficacy of antibiotics through both acquired resistance and tolerance. In this study, a pan-drug resistant (PDR), NDM-1 and CTX-M-15 co-producing isolate of K. pneumoniae, CDC Nevada, (Kp Nevada) was exposed to the clinical combination of aztreonam + ceftazidime/avibactam (ATM/CAZ/AVI) to overcome metallo-ß-lactamases. Unexpectedly, the ß-lactam combination resulted in long filamentous cell formation induced by PBP3 inhibition over 168 h in the hollow fiber infection model experiments with eventual reversion of the total population upon drug removal. However, the addition of imipenem to the two drug ß-lactam combination was highly synergistic with suppression of all drug resistant subpopulations over 5 days. Scanning electron microscopy and fluorescence microscopy for all imipenem combinations in time kill studies suggested a role for imipenem in suppression of long filamentous persisters, via the formation of metabolically active spheroplasts. To complement the imaging studies, salient transcriptomic changes were quantified using RT-PCR and novel cassette assay evaluated ß-lactam permeability. This showed significant upregulation of both spheroplast protein Y (SPY), a periplasmic chaperone protein that has been shown to be related to spheroplast formation, and penicillin binding proteins (PBP1, PBP2, PBP3) for all combinations involving imipenem. However, with aztreonam alone, pbp1, pbp3 and spy remained unchanged while pbp2 levels were downregulated by > 25%. Imipenem displayed 207-fold higher permeability as compared with aztreonam (mean permeability coefficient of 17,200 nm/s). Although the clinical combination of aztreonam/avibactam and ceftazidime has been proposed as an important treatment of MBL Gram-negatives, we report the first occurrence of long filamentous persister formation. To our knowledge, this is the first study that defines novel ß-lactam combinations involving imipenem via maximal suppression of filamentous persisters to combat PDR CDC Nevada K. pneumoniae.

Mapping the global distribution of C4 vegetation using observations and optimality theory.

Plants with the C4 photosynthesis pathway typically respond to climate change differently from more common C3-type plants, due to their distinct anatomical and biochemical characteristics. These different responses are expected to drive changes in global C4 and C3 vegetation distributions. However, current C4 vegetation distribution models may not predict this response as they do not capture multiple interacting factors and often lack observational constraints. Here, we used global observations of plant photosynthetic pathways, satellite remote sensing, and photosynthetic optimality theory to produce an observation-constrained global map of C4 vegetation. We find that global C4 vegetation coverage decreased from 17.7% to 17.1% of the land surface during 2001 to 2019. This was the net result of a reduction in C4 natural grass cover due to elevated CO2 favoring C3-type photosynthesis, and an increase in C4 crop cover, mainly from corn (maize) expansion. Using an emergent constraint approach, we estimated that C4 vegetation contributed 19.5% of global photosynthetic carbon assimilation, a value within the range of previous estimates (18-23%) but higher than the ensemble mean of dynamic global vegetation models (14 ± 13%; mean ± one standard deviation). Our study sheds insight on the critical and underappreciated role of C4 plants in the contemporary global carbon cycle.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in New Zealand: peri-operative outcomes and service development over a decade.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard of care for selected cases of peritoneal surface malignancy. However, due to its morbidity and learning curve, it is only delivered in six centres in Australia and Aotearoa New Zealand (AoNZ). In this study, we report peri-operative morbidity and mortality following CRS/HIPEC at Waikato and Braemar Hospitals, which have treated patients from all regions of AoNZ since 2008. METHODS: We retrospectively reviewed a database of all patients undergoing CRS and HIPEC from 01/01/2008 to 01/11/2020 at Waikato and Braemar Hospitals. RESULTS: Two-hundred and forty procedures were performed for 221 patients with a mean age of 55, including 22 (9.2%) re-do procedures. One hundred and eighty-six cases were European, 32 were Maori, and 16 were Pasifika. There were 152 pseudomyxoma peritonei, 39 colorectal adenocarcinomas, 29 appendiceal cancers, 8 ovarian cancers, 6 peritoneal mesothelioma, and 6 other tumour types. The median PCI was 16. HIPEC was administered to 196 out of 196 CC0/1 cases (100%) and 3 out of 44 CC2/3 cases (6.8%). Fifty-six cases (23.3%) had at least one major complication. There were two mortalities (0.8%) within 30 days. The median length of stay was 11 days. Operative duration was identified as an independent risk factor for major complications. There was considerable variation in the number of referrals from different regions of AoNZ. Over time, a decline in major complication rate is seen with increased case volume. CONCLUSION: The Waikato region has achieved favourable short-term outcomes following CRS/HIPEC.