Alignment-free Genomic Analysis via a Big Data Spark Platform

Motivation: Alignment-free distance and similarity functions (AF functions, for short) are a well established alternative to two and multiple sequence alignments for many genomic, metagenomic and epigenomic tasks. Due to data-intensive applications, the computation of AF functions is a Big Data problem, with the recent Literature indicating that the development of fast and scalable algorithms computing AF functions is a high-priority task. Somewhat surprisingly, despite the increasing popularity of Big Data technologies in Computational Biology, the development of a Big Data platform for those tasks has not been pursued, possibly due to its complexity. Results: We fill this important gap by introducing FADE, the first extensible, efficient and scalable Spark platform for Alignment-free genomic analysis. It supports natively eighteen of the best performing AF functions coming out of a recent hallmark benchmarking study. FADE development and potential impact comprises novel aspects of interest. Namely, (a) a considerable effort of distributed algorithms, the most tangible result being a much faster execution time of reference methods like MASH and FSWM; (b) a software design that makes FADE user-friendly and easily extendable by Spark non-specialists; (c) its ability to support data- and compute-intensive tasks. About this, we provide a novel and much needed analysis of how informative and robust AF functions are, in terms of the statistical significance of their output. Our findings naturally extend the ones of the highly regarded benchmarking study, since the functions that can really be used are reduced to a handful of the eighteen included in FADE

FASTA/Q data compressors for MapReduce-Hadoop genomics: space and time savings made easy

Background Storage of genomic data is a major cost for the Life Sciences, effectively addressed via specialized data compression methods. For the same reasons of abundance in data production, the use of Big Data technologies is seen as the future for genomic data storage and processing, with MapReduce-Hadoop as leaders. Somewhat surprisingly, none of the specialized FASTA/Q compressors is available within Hadoop. Indeed, their deployment there is not exactly immediate. Such a State of the Art is problematic. Results We provide major advances in two different directions. Methodologically, we propose two general methods, with the corresponding software, that make very easy to deploy a specialized FASTA/Q compressor within MapReduce-Hadoop for processing files stored on the distributed Hadoop File System, with very little knowledge of Hadoop. Practically, we provide evidence that the deployment of those specialized compressors within Hadoop, not available so far, results in better space savings, and even in better execution times over compressed data, with respect to the use of generic compressors available in Hadoop, in particular for FASTQ files. Finally, we observe that these results hold also for the Apache Spark framework, when used to process FASTA/Q files stored on the Hadoop File System. Conclusions Our Methods and the corresponding software substantially contribute to achieve space and time savings for the storage and processing of FASTA/Q files in Hadoop and Spark. Being our approach general, it is very likely that it can be applied also to FASTA/Q compression methods that will appear in the future

Rank-Similarity Measures for Comparing Gene Prioritizations: A Case Study in Autism

We discuss the challenge of comparing three gene prioritization methods: network propagation, integer linear programming rank aggregation (RA), and statistical RA. These methods are based on different biological categories and estimate disease?gene association. Previously proposed comparison schemes are based on three measures of performance: receiver operating curve, area under the curve, and median rank ratio. Although they may capture important aspects of gene prioritization performance, they may fail to capture important differences in the rankings of individual genes. We suggest that comparison schemes could be improved by also considering recently proposed measures of similarity between gene rankings. We tested this suggestion on comparison schemes for prioritizations of genes associated with autism that were obtained using brain- and tissue-specific data. Our results show the effectiveness of our measures of similarity in clustering brain regions based on their relevance to autism

Emilia-Romagna Surgical Colorectal Cancer Audit (ESCA): a value-based healthcare retro-prospective study to measure and improve the quality of surgical care in colorectal cancer

Purpose: Surgery is the main treatment for non-metastatic colorectal cancer. Despite huge improvements in perioperative care, colorectal surgery is still associated with a significant burden of postoperative complications and ultimately costs for healthcare organizations. Systematic clinical auditing activity has already proven to be effective in measuring and improving clinical outcomes, and for this reason, we decided to evaluate its impact in a large area of northern Italy. Methods: The Emilia-Romagna Surgical Colorectal Audit (ESCA) is an observational, multicentric, retro-prospective study, carried out by 7 hospitals located in the Emilia-Romagna region. All consecutive patients undergoing surgery for colorectal cancer during a 54-month study period will be enrolled. Data regarding baseline conditions, preoperative diagnostic work-up, surgery and postoperative course will be collected in a dedicated case report form. Primary outcomes regard postoperative complications and mortality. Secondary outcomes include each center’s adherence to the auditing (enrolment rate) and evaluation of the systematic feedback activity on key performance indicators for the entire perioperative process. Conclusion: This protocol describes the methodology of the Emilia-Romagna Surgical Colorectal Audit. The study will provide real-world clinical data essential for benchmarking and feedback activity, to positively impact outcomes and ultimately to improve the entire healthcare process of patients undergoing colorectal cancer surgery. Clinical trial registration: The study ESCA is registered on the clinicaltrials.gov platform (Identifier: NCT03982641)

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Gastro-intestinal emergency surgery: Evaluation of morbidity and mortality. Protocol of a prospective, multicenter study in Italy for evaluating the burden of abdominal emergency surgery in different age groups. (The GESEMM study)

Gastrointestinal emergencies (GE) are frequently encountered in emergency department (ED), and patients can present with wide-ranging symptoms. more than 3 million patients admitted to US hospitals each year for EGS diagnoses, more than the sum of all new cancer diagnoses. In addition to the complexity of the urgent surgical patient (often suffering from multiple co-morbidities), there is the unpredictability and the severity of the event. In the light of this, these patients need a rapid decision-making process that allows a correct diagnosis and an adequate and timely treatment. The primary endpoint of this Italian nationwide study is to analyze the clinicopathological findings, management strategies and short-term outcomes of gastrointestinal emergency procedures performed in patients over 18. Secondary endpoints will be to evaluate to analyze the prognostic role of existing risk-scores to define the most suitable scoring system for gastro-intestinal surgical emergency. The primary outcomes are 30-day overall postoperative morbidity and mortality rates. Secondary outcomes are 30-day postoperative morbidity and mortality rates, stratified for each procedure or cause of intervention, length of hospital stay, admission and length of stay in ICU, and place of discharge (home or rehabilitation or care facility). In conclusion, to improve the level of care that should be reserved for these patients, we aim to analyze the clinicopathological findings, management strategies and short-term outcomes of gastrointestinal emergency procedures performed in patients over 18, to analyze the prognostic role of existing risk-scores and to define new tools suitable for EGS. This process could ameliorate outcomes and avoid futile treatments. These results may potentially influence the survival of many high-risk EGS procedure

Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P <0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research