Chemoinformatic regression methods and their applicability domain.

The growing interest in chemoinformatic model uncertainty calls for a summary of the most widely used regression techniques and how to estimate their reliability. Regression models learn a mapping from the space of explanatory variables to the space of continuous output values. Among other limitations, the predictive performance of the model is restricted by the training data used for model fitting. Identification of unusual objects by outlier detection methods can improve model performance. Additionally, proper model evaluation necessitates defining the limitations of the model, often called the applicability domain. Comparable to certain classifiers, some regression techniques come with built-in methods or augmentations to quantify their (un)certainty, while others rely on generic procedures. The theoretical background of their working principles and how to deduce specific and general definitions for their domain of applicability shall be explained.

Antiarrhythmic preferences and outcomes post DC cardioversion for atrial fibrillation, an Australian rural perspective.

INTRODUCTION: Direct current cardioversion (DCCV) remains one of the recommended management strategies for symptomatic atrial fibrillation (AF). Antiarrhythmic drugs (AAD) are prescribed post procedure to maintain sinus rhythm (SR). Limited literature exists on the AAD prescribing practices and their efficacy, post-DCCV in rural Australia. OBJECTIVE: The primary aim was to determine the preferred AAD post-DCCV and the factors affecting AAD prescribing practices. The secondary aim was to assess the efficacy of the AAD in maintaining SR. DESIGN: A retrospective observational audit of patients with non-valvular AF who underwent successful elective DCCV for symptomatic AF, during 2015-2020 at a regional hospital in New South Wales (NSW) (Dubbo Base Hospital). Patients were followed up for a duration of 12 months post-DCCV. RESULTS: 233 patients underwent successful DCCV during the study duration. Amiodarone was the preferred AAD of choice post-DCCV followed by sotalol and flecainide, respectively (36.5% vs. 27.8% vs. 1.3%). 35.2% patients were not prescribed AAD. Amiodarone and sotalol had similar but modest efficacies and neither were superior to no AAD, in maintaining SR 12 months post-DCCV (AF recurrence rate 61.5% vs. 68.2% vs. 71.6% respectively, p = 0.37). Antecedent cerebrovascular accident (CVA), pulmonary disease, smoking, prior treatment with digoxin, diuretics and left ventricular (LV) dysfunction were factors that influenced AAD prescribing practices. CONCLUSION: The study demonstrates equal efficacies of amiodarone, sotalol and no AAD in maintaining SR 12 months post-DCCV. Prescribing practices post-DCCV at Dubbo Base Hospital differ from observed national trends and guidelines. AAD prescription requires a multifaceted approach with a key consideration to prioritise safety over efficacy, being mindful of challenges in delivering optimal healthcare in a rural setting.

Homozygous ALS-linked mutations in TARDBP/TDP-43 lead to hypoactivity and synaptic abnormalities in human iPSC-derived motor neurons.

Cytoplasmic mislocalization and aggregation of the RNA-binding protein TDP-43 is a pathological hallmark of the motor neuron (MN) disease amyotrophic lateral sclerosis (ALS). Furthermore, while mutations in TARDBP (encoding TDP-43) have been associated with ALS, the pathogenic consequences of these mutations remain poorly understood. Using CRISPR-Cas9, we engineered two homozygous knock-in induced pluripotent stem cell lines carrying mutations in TARDBP encoding TDP-43A382T and TDP-43G348C, two common yet understudied ALS TDP-43 variants. Motor neurons (MNs) differentiated from knock-in iPSCs had normal viability and displayed no significant changes in TDP-43 subcellular localization, phosphorylation, solubility, or aggregation compared with isogenic control MNs. However, our results highlight synaptic impairments in both TDP-43A382T and TDP-43G348C MN cultures, as reflected in synapse abnormalities and alterations in spontaneous neuronal activity. Collectively, our findings suggest that MN dysfunction may precede the occurrence of TDP-43 pathology and neurodegeneration in ALS and further implicate synaptic and excitability defects in the pathobiology of this disease.

Deep neural networks can differentiate thyroid pathologies on infrared hyperspectral images.

BACKGROUND AND OBJECTIVE: The thyroid is a gland responsible for producing important body hormones. Several pathologies can affect this gland, such as thyroiditis, hypothyroidism, and thyroid cancer. The visual histological analysis of thyroid specimens is a valuable process that enables pathologists to detect diseases with high efficiency, providing the patient with a better prognosis. Existing computer vision systems developed to aid in the analysis of histological samples have limitations in distinguishing pathologies with similar characteristics or samples containing multiple diseases. To overcome this challenge, hyperspectral images are being studied to represent biological samples based on their molecular interaction with light. METHODS: In this study, we address the acquisition of infrared absorbance spectra from each voxel of histological specimens. This data is then used for the development of a multiclass fully-connected neural network model that discriminates spectral patterns, enabling the classification of voxels as healthy, cancerous, or goiter. RESULTS: Through experiments using the k-fold cross-validation protocol, we obtained an average accuracy of 93.66 %, a sensitivity of 93.47 %, and a specificity of 96.93 %. Our results demonstrate the feasibility of using infrared hyperspectral imaging to characterize healthy tissue and thyroid pathologies using absorbance measurements. The proposed deep learning model has the potential to improve diagnostic efficiency and enhance patient outcomes.

CDNA-SNN: A New Spiking Neural Network for Pattern Classification Using Neuronal Assemblies.

Spiking neural networks (SNNs) mimic their biological counterparts more closely than their predecessors and are considered the third generation of artificial neural networks. It has been proven that networks of spiking neurons have a higher computational capacity and lower power requirements than sigmoidal neural networks. This article introduces a new type of SNN that draws inspiration and incorporates concepts from neuronal assemblies in the human brain. The proposed network, termed as class-dependent neuronal activation-based SNN (CDNA-SNN), assigns each neuron learnable values known as CDNAs which indicate the neuron's average relative spiking activity in response to samples from different classes. A new learning algorithm that categorizes the neurons into different class assemblies based on their CDNAs is also presented. These neuronal assemblies are trained via a novel training method based on spike-timing-dependent plasticity (STDP) to have high activity for their associated class and low firing rate for other classes. Also, using CDNAs, a new type of STDP that controls the amount of plasticity based on the assemblies of pre-and postsynaptic neurons is proposed. The performance of CDNA-SNN is evaluated on five datasets from the University of California, Irvine (UCI) machine learning repository, as well as Modified National Institute of Standards and Technology (MNIST) and Fashion MNIST, using nested cross-validation (N-CV) for hyperparameter optimization. Our results show that CDNA-SNN significantly outperforms synaptic weight association training (SWAT) ( p 0.0005) and SpikeProp ( p 0.05) on 3/5 and self-regulating evolving spiking neural (SRESN) ( p 0.05) on 2/5 UCI datasets while using the significantly lower number of trainable parameters. Furthermore, compared to other supervised, fully connected SNNs, the proposed SNN reaches the best performance for Fashion MNIST and comparable performance for MNIST and neuromorphic-MNIST (N-MNIST), also utilizing much less (1%-35%) parameters.

Structural Foot Characteristics in People With Midfoot Osteoarthritis: Cross-Sectional Findings From the Clinical Assessment Study of the Foot.

OBJECTIVE: This study compared radiographic measures of foot structure between people with and without symptomatic radiographic midfoot osteoarthritis (OA). METHODS: This was a cross-sectional study of adults aged 50 years and older registered with four UK general practices who reported foot pain in the past year. Bilateral weightbearing dorsoplantar and lateral radiographs were obtained. Symptomatic radiographic midfoot OA was defined as midfoot pain in the last 4 weeks, combined with radiographic OA in one or more midfoot joints (first cuneometatarsal, second cuneometatarsal, navicular-first cuneiform, and talonavicular). Midfoot OA cases were matched 1:1 for sex and age to controls with a 5-year age tolerance. Eleven radiographic measures were extracted and compared between the groups using independent sample t-tests and effect sizes (Cohen's d). RESULTS: We identified 63 midfoot OA cases (mean ± SD age was 66.8 ± 8.0 years, with 32 male and 31 female participants) and matched these to 63 controls (mean ± SD age was 65.9 ± 7.8 years). There were no differences in metatarsal lengths between the groups. However, those with midfoot OA had a higher calcaneal-first metatarsal angle (d = 0.43, small effect size, P = 0.018) and lower calcaneal inclination angle (d = 0.46, small effect size, P = 0.011) compared with controls. CONCLUSIONS: People with midfoot OA have a flatter foot posture compared with controls. Although caution is required when inferring causation from cross-sectional data, these findings are consistent with a pathomechanical pathway linking foot structure to the development of midfoot OA. Prospective studies are required to determine the temporal relationships between foot structure, function, and the development of this common and disabling condition.

Plantar pressures in people with midfoot osteoarthritis: cross-sectional findings from the Clinical Assessment Study of the Foot.

BACKGROUND: Midfoot osteoarthritis (OA) is a common condition, however its aetiology is not well understood. Understanding how plantar pressures differ between people with and without midfoot OA may provide insight into the aetiology and how best to manage this condition. RESEARCH QUESTION: To compare plantar pressures between people with and without symptomatic radiographic midfoot OA. METHODS: This was a cross-sectional study of adults aged ≥ 50 years registered with four UK general practices who reported foot pain in the past year. Symptomatic radiographic midfoot OA was defined as midfoot pain in the last four weeks, combined with radiographic OA in one or more midfoot joints. Cases were matched 1:1 for sex and age ( ± 5 years) to controls. Peak plantar pressure and maximum force in 10 regions of the foot were determined using a pressure platform (RSscan International, Olen, Belgium) and compared between the groups using independent samples t-tests and effect sizes (Cohen's d). RESULTS: We included 61 midfoot OA cases (mean age 67.0, SD 8.1, 31 males, 30 females) and matched these to 61 controls (mean age 66.0, SD 7.9). Midfoot OA cases displayed greater force (d=0.79, medium effect size, p = <0.001) and pressure at the midfoot (d=0.70, medium effect size, p = <0.001), greater force at the fourth metatarsophalangeal (MTP) joint (d=0.28, small effect size, p = 0.13), and fifth MTP joint (d=0.37, small effect size, p = 0.10) and greater pressure at the fifth MTP joint (d=0.34, small effect size, p = 0.13). They also displayed lower force (d=0.40, small effect size, p = 0.02) and pressure at the hallux (d=0.50, medium effect size, p = <0.001) and lower force (d=0.54, medium effect size, p = <0.001) and pressure at the lesser toes (d=0.48, small effect size, p = <0.001) compared with controls. SIGNIFICANCE: Midfoot OA appears to be associated with lowering of the medial longitudinal arch, greater lateral push off and less propulsion at toe off. Longitudinal studies are needed to establish causal relationships.

The problem of antimalarial resistance and its implications for drug discovery.

INTRODUCTION: Malaria remains a devastating infectious disease with hundreds of thousands of casualties each year. Antimalarial drug resistance has been a threat to malaria control and elimination for many decades and is still of concern today. Despite the continued effectiveness of current first-line treatments, namely artemisinin-based combination therapies, the emergence of drug-resistant parasites in Southeast Asia and even more alarmingly the occurrence of resistance mutations in Africa is of great concern and requires immediate attention. AREAS COVERED: A comprehensive overview of the mechanisms underlying the acquisition of drug resistance in Plasmodium falciparum is given. Understanding these processes provides valuable insights that can be harnessed for the development and selection of novel antimalarials with reduced resistance potential. Additionally, strategies to mitigate resistance to antimalarial compounds on the short term by using approved drugs are discussed. EXPERT OPINION: While employing strategies that utilize already approved drugs may offer a prompt and cost-effective approach to counter antimalarial drug resistance, it is crucial to recognize that only continuous efforts into the development of novel antimalarial drugs can ensure the successful treatment of malaria in the future. Incorporating resistance propensity assessment during this developmental process will increase the likelihood of effective and enduring malaria treatments.

A scoping review of patient self-report measures of flare in knee and hip osteoarthritis (OA): A report from the OMERACT flares in OA working group.

PURPOSE: We aimed to analyze the content validity/domain match and feasibility of self-report instruments that could measure flare in osteoarthritis (OA), by extending our 2017 literature review on the definition of flare in knee and hip OA. METHOD: We searched PubMed (Medline), Web of Science and PsycInfo (Ebsco Host) databases for original articles reporting research about flare (or synonyms) in humans with knee and hip OA, between 2017 and 2023. Four experts worked independently, checking the records, and assessing content validity and feasibility, writing justification for exclusion. RESULTS: At literature review phase, 575 papers were filtered. After experts' analysis, 59 studies were included, and 44 instruments associated with flare in OA were identified. Most were studies about pain in knee or hip OA (35 %), cultural adaptation of a measure (33 %) or studies investigating psychometric properties of full (16 %) or short form (4 %) instruments. The assessment of domain match and feasibility revealed that 15 instruments were assigned a label of 'yes' or 'uncertain' as to whether or not there was a good match with the domain concept or whether the instrument was considered feasible to use. DISCUSSION: Most identified instruments considered different aspects of pain and the associated discomfort in performing daily activities but did not include the central aspects of flare in OA, i.e. the change of state, nor the additional Outcome Measures in Rheumatology (OMERACT) endorsed domains for OA flare namely stiffness, swelling, psychological aspects, impact of symptoms including fatigue and sleep disturbance. Although it is possible that the period specified to conduct this literature review may have led to some recognized instruments being excluded, this review demonstrates the need for the research community to reach consensus on the best way to measure self-reported flares in future clinical trials and observational studies.

Exploring the potential of incremental feature selection to improve genomic prediction accuracy.

BACKGROUND: The ever-increasing availability of high-density genomic markers in the form of single nucleotide polymorphisms (SNPs) enables genomic prediction, i.e. the inference of phenotypes based solely on genomic data, in the field of animal and plant breeding, where it has become an important tool. However, given the limited number of individuals, the abundance of variables (SNPs) can reduce the accuracy of prediction models due to overfitting or irrelevant SNPs. Feature selection can help to reduce the number of irrelevant SNPs and increase the model performance. In this study, we investigated an incremental feature selection approach based on ranking the SNPs according to the results of a genome-wide association study that we combined with random forest as a prediction model, and we applied it on several animal and plant datasets. RESULTS: Applying our approach to different datasets yielded a wide range of outcomes, i.e. from a substantial increase in prediction accuracy in a few cases to minor improvements when only a fraction of the available SNPs were used. Compared with models using all available SNPs, our approach was able to achieve comparable performances with a considerably reduced number of SNPs in several cases. Our approach showcased state-of-the-art efficiency and performance while having a faster computation time. CONCLUSIONS: The results of our study suggest that our incremental feature selection approach has the potential to improve prediction accuracy substantially. However, this gain seems to depend on the genomic data used. Even for datasets where the number of markers is smaller than the number of individuals, feature selection may still increase the performance of the genomic prediction. Our approach is implemented in R and is available at https://github.com/FelixHeinrich/GP_with_IFS/ .

[Customized partial pelvis replacement: three-dimensional planning and management concepts]. / Individuelle Beckenteilersatz-Implantate: 3-D-Planung und Versorgungskonzepte.

The planning and implantation of a customized partial pelvis replacement places high demands on both the surgeon and the entire team (engineer, assistants, surgical team). Thanks to careful preoperative planning and meticulous perioperative execution, customized partial pelvic replacement represents a complex but reliable procedure for defect reconstruction even with highly complex acetabular bone defects or after multiple previous surgeries.

COVID-19 measures as an opportunity to reduce the environmental footprint in orthopaedic and trauma surgery.

Background: Climate change and its consequences on our everyday life have also tremendous impacts on public health and the health of each individual. The healthcare sector currently accounts for 4.4% of global greenhouse gas emissions. The share of the emissions in the health care system caused by the transportation sector is 7%. The study analyses the effect of video consultation on the CO2 emissions during the Covid-19 pandemic in an outpatient clinic of the department of orthopaedics and traumatology surgery at a German university hospital. Methods: The study participants were patients who obtained a video consultation in the period from June to December 2020 and voluntarily completed a questionnaire after the consultation. The type of transport, travel time and waiting time as well as patient satisfaction were recorded by questionnaire. Results: The study comprised 51 consultations. About 70% of respondents would have travelled to the clinic by car. The reduction in greenhouse gas emissions of video consultations compared to a face-to-face presentation was 97% in our model investigation. Conclusion: The video consultation can be a very important part of the reduction of greenhouse gas emissions in the health care system. It also saves time for the doctor and patient and can form an essential part of individual patient care.

Temporary arthrodesis through static spacer implantation in two-stage treatment of periprosthetic joint infections of the knee.

OBJECTIVE: Treatment of chronic periprosthetic joint infection of the knee requires the removal of the implant and thorough debridement, with reimplantation in a second stage surgery. Intramedullary spacers can be helpful during the interval between explantation and reimplantation and provide a temporary arthrodesis which fixes the knee in extension preserving leg length and administers local antibiotic therapy. INDICATIONS: Periprosthetic joint infection of the knee with large bony defects and severe infection of the native joint with advanced destruction/infiltration of the cartilage and bone and/or ligament insufficiency. CONTRAINDICATIONS: Suspected antibiotic resistance of the microbiological pathogen to local antibiotic drugs, incompliant patient, and known allergy to bone cement or antibiotic. SURGICAL TECHNIQUE: After implant removal, suitable metal rods are coated with antibiotic-loaded bone cement and inserted into the cleaned intramedullary canals of femur and tibia. Rods are joined at the joint line with a connector and joint space is filled with more bone cement to achieve temporary and very stable arthrodesis. POSTOPERATIVE MANAGEMENT: Partial weight-bearing and no flexion/extension while spacer is in place; second stage reimplantation as soon as infection is controlled. RESULTS: Complications related to the spacer were rare (5.3%). Reimplantation of an implant was possible in 95 of 113 patients (84%), of those, 23 (20%) received an arthrodesis. Of the 95 patients that were reimplanted, 14 showed signs of recurrent infection. Mean time to last follow-up was 15.6 months post reimplantation. Mean knee pain was 2.9/10; overall function was good; 6 patients had an extension lag; mean total range of motion was 88°.

An Evaluation of Different Strategies for Sampling Controls in an Online Case-Crossover Study of Acute Flares in Knee Osteoarthritis.

Objective: To evaluate bias and precision of exposure-outcome effect estimates from three control sampling strategies in a case-crossover study. Methods: Online case-crossover study investigating eight physical activity-related triggers for acute flares in knee osteoarthritis. Exposures were measured in hazard periods (≤24 hours before self-declared flare onset). Control period exposure was measured in three ways: (1) four scheduled questionnaires over 13-weeks, (2) "usual" physical activity levels ascertained at baseline, (3) over three days before flare onset. Derived odds ratios, 95% confidence intervals and standard errors were compared. Results: Of 744 participants (mean age 62.1 [SD 10.2] years; 61% female), 493 reported 714 flares. Selecting controls from scheduled questionnaires, independent of hazard periods, yielded predominantly odds ratios in the expected direction (exposure "a lot" versus exposure "not at all", range: 0.57-3.22). When controls were sampled at baseline (range: 0.01-1.42) or immediately before a flare (range: 0.30-1.27) most odds ratio estimates were inverted. Standard errors of the log odds ratios were smallest when controls were sampled from scheduled questionnaires (range: 0.264-0.473) compared to controls sampled at baseline (range: 0.267-0.589) or immediately before a flare (range: 0.319-0.621). Conclusion: Our findings are sensitive to control sample selection. Under certain conditions, different patterns could be attributed to over reporting and social desirability bias, where people may want to present themselves more positively about their "usual" physical activity levels, at baseline. Exposure measurement at the time of a flare may be less precise and more susceptible to recall bias due to systematically reporting exposures differently during a flare, compared to control measurement independent of flares.

Surgical technique and preliminary results of a moulded, mobile spacer for the treatment of periprosthetic joint infection of the knee.

OBJECTIVE: Mobile knee spacers can be utilized in the first stage of a two-stage exchange in periprosthetic joint infection or septic arthritis of the knee to prevent soft tissue contraction, enable local antibiotic elution, and improve patient mobility. Commercially made moulds enable the surgeon to prepare a reproducible spacer design and match the preparation of the arthroplasty, which will be carried out in a second step. INDICATIONS: Periprosthetic joint infection of the knee and severe cases of septic arthritis of the knee with advanced destruction/infiltration of the cartilage. CONTRAINDICATIONS: Antibiotic resistance of the microbiological pathogen to available antibiotic agents, incompliant patient, large osseous defect preventing proper fixation, known allergy to polymethylmethacrylate (PMMA) or antibiotic, severe soft tissue damage with high ligament instability, especially deterioration of extensor mechanism and insufficient patella/quadricep tendon. SURGICAL TECHNIQUE: After thorough debridement and removal of all foreign material, cutting blocks are used to shape femur and tibia to the implant design required. Using a silicone mould, PMMA with suitable antibiotics is moulded into the shape of the future implant. After polymerization, the implants are fixed onto the bone with additional PMMA without pressurize for the sake of easy removal. POSTOPERATIVE MANAGEMENT: Partial weight bearing with no restriction of flexion/extension while spacer is in place; second stage reimplantation as soon as infection is controlled. RESULTS: In all, 22 cases were treated, mostly with a PMMA spacer containing gentamicin and vancomycin. Pathogens were detected in 13 of 22 cases (59%). We observed two complications (9%). Twenty of 22 patients (86%) were reimplanted with a new arthroplasty; 16 of the 20 patients remained revision-free and infection-free at the last follow-up (average time to follow-up 13 months, range 1-46 months). Average range of motion in flexion and extension at follow-up was 98°.

Large-scale evaluation of k-fold cross-validation ensembles for uncertainty estimation.

It is insightful to report an estimator that describes how certain a model is in a prediction, additionally to the prediction alone. For regression tasks, most approaches implement a variation of the ensemble method, apart from few exceptions. Instead of a single estimator, a group of estimators yields several predictions for an input. The uncertainty can then be quantified by measuring the disagreement between the predictions, for example by the standard deviation. In theory, ensembles should not only provide uncertainties, they also boost the predictive performance by reducing errors arising from variance. Despite the development of novel methods, they are still considered the "golden-standard" to quantify the uncertainty of regression models. Subsampling-based methods to obtain ensembles can be applied to all models, regardless whether they are related to deep learning or traditional machine learning. However, little attention has been given to the question whether the ensemble method is applicable to virtually all scenarios occurring in the field of cheminformatics. In a widespread and diversified attempt, ensembles are evaluated for 32 datasets of different sizes and modeling difficulty, ranging from physicochemical properties to biological activities. For increasing ensemble sizes with up to 200 members, the predictive performance as well as the applicability as uncertainty estimator are shown for all combinations of five modeling techniques and four molecular featurizations. Useful recommendations were derived for practitioners regarding the success and minimum size of ensembles, depending on whether predictive performance or uncertainty quantification is of more importance for the task at hand.

Commercially manufactured spacers for the treatment of periprosthetic joint infection of the hip.

BACKGROUND: Periprosthetic joint infection remains a common and serious complication after hip arthroplasty. To improve function and patient comfort after joint removal in two-stage revision, commercially manufactured spacers for the hip joint allow retention of the anatomical joint geometry thereby limiting soft tissue contraction and allow mobilization. INDICATIONS: Periprosthetic joint infection of the hip, septic arthritis with severe destruction of the hip cartilage and/or bone requiring arthroplasty. CONTRAINDICATIONS: Allergies to polymethylmethacrylate (PMMA) or antibiotics, severe hip dysplasia with insufficient cranial support, incompliant patient, large osseous defect of the acetabulum, insufficient metaphyseal/diaphyseal support of the femoral bone, resistance of the microbiological pathogen to spacer-inert antibiotic medication, inability to perform primary wound closure requiring temporary open-wound therapy. SURGICAL TECHNIQUE: Preoperative templating on radiograph; removal of joint prosthesis and thorough debridement with removal of all foreign material; trial spacer selection and insertion and trial reduction of the joint, fixing the spacer with PMMA to the proximal femur, final reduction, radiograph and stability test. RESULTS: Data were analyzed from patients treated between 2016 and 2021. In all, 20 patients were treated with preformed spacers and 16 with custom-made spacers. Pathogens were detected in 23 of the 36 cases (64%). Polymicrobial infections were present in 8 of 36 cases (22%). In patients who received preformed spacers, there were 6 cases of spacer-related complications (30%). Of the 36 patients (83%), 30 were reimplanted with a new implant; 3 patients died due to septic or other complications before reimplantation (8%). Average follow-up was 20.2 months after reimplantation. There were no major differences between the two groups of spacers. Patient comfort was not measured.

Enhanced recovery pathway in open and minimally invasive colorectal cancer surgery: a prospective study on feasibility, compliance, and outcomes in a high-volume resource limited tertiary cancer center.

BACKGROUND: Enhanced recovery program (ERP) has demonstrated improved postoperative outcomes with increased compliance to pathway. However, there is scarce data on feasibility and safety in resource limited setting. The objective was to assess compliance with ERP and its impact on postoperative outcomes and return to intended oncological treatment (RIOT). METHODS: A single center prospective observational audit was conducted from 2014 to 2019, in elective colorectal cancer surgery. Before implementation, multi-disciplinary team was educated regarding ERP. Compliance to ERP protocol and its elements was recorded. Impact of quantum of compliance (≥80% vs. <80%) to ERP on postoperative morbidity, mortality, readmission, stay, re-exploration, functional GI recovery, surgical-specific complications, and RIOT was evaluated for open and minimal invasive surgery (MIS). RESULTS: During study, 937 patients underwent elective colorectal cancer surgery. Overall compliance with ERP was 73.3%. More than 80% compliance was observed in 332 (35.4%) patients in the entire cohort. Patients with <80% compliance had significantly higher overall, minor and surgery-specific complications, longer postoperative stay, delayed functional GI recovery for both open and MIS procedures. RIOT was observed in 96.5% patients. Duration to RIOT was significantly shorter following open surgery with ≥80% compliance. Compliance <80% to ERP was identified as one of the independent predictors for developing postoperative complications. CONCLUSION: The study demonstrates beneficial impact of increased compliance to ERP on postoperative outcomes following open and minimally invasive surgery for colorectal cancer. Within a resource limited setting, ERP was found to feasible, safe, and effective in both open and minimally invasive colorectal cancer surgery.