Long-term combination therapy with metformin and oxymetholone in a Fanconi anemia mouse model.

Fanconi anemia (FA) is a disease caused by defective deoxyribonucleic acid (DNA) repair that manifests as bone marrow failure, cancer predisposition, and developmental defects. We previously reported that monotherapy with either metformin (MET) or oxymetholone (OXM) improved peripheral blood (PB) counts and the number and functionality of bone marrow hematopoietic stem progenitor cells (HSPCs) number in Fancd2-/- mice. To evaluate whether the combination treatment of these drugs has a synergistic effect to prevent bone marrow failure in FA, we treated cohorts of Fancd2-/- mice and wildtype controls with either MET alone, OXM alone, MET+OXM, or placebo diet from age 3 weeks to 18 months. The OXM treated animals showed modest improvements in blood parameters including platelet count (p = .01) and hemoglobin levels (p < .05). In addition, the percentage of quiescent hematopoietic stem cell (HSC) (LSK [Lin-Sca+c-Kit+]) was significantly increased (p = .001) by long-term treatment with MET alone. The combination of metformin and oxymetholone did not result in a significant synergistic effect in any hematopoietic parameter. Gene expression analysis of liver tissue from these animals showed that some of the expression changes caused by Fancd2 deletion were partially normalized by metformin treatment. Importantly, no adverse effects of the individual or combination therapies were observed, despite the long-term administration. We conclude that androgen therapy is not a contraindication to concurrent metformin administration in clinical trials. HIGHLIGHTS: Long-term coadministration of metformin in combination with oxymetholone is well tolerated by Fancd2-/- mice. Hematopoietic stem cell quiescence in mutant mice was enhanced by treatment with metformin alone. Metformin treatment caused a partial normalization of gene expression in the livers of mutant mice.

Long-term combination therapy with Metformin and Oxymetholone in a Fanconi Anemia mouse model.

Fanconi Anemia (FA) is a disease caused by defective DNA repair which manifests as bone marrow failure, cancer predisposition, and developmental defects. Mice containing inactivating mutations in one or more genes in the FA pathway partially mimic the human disease. We previously reported that monotherapy with either metformin (MET) or oxymetholone (OXM) improved peripheral blood (PB) counts and the number and functionality of bone marrow (BM) hematopoietic stem progenitor cells (HSPCs) number in Fancd2-/- mice. To evaluate whether the combination treatment of these drugs has a synergistic effect to prevent bone marrow failure in FA, we treated cohorts of Fancd2-/- mice and wild-type controls with either MET alone, OXM alone, MET+OXM or placebo diet. Both male and female mice were treated from age 3 weeks to 18 months. The OXM treated animals showed modest improvements in blood parameters including platelet count (p=0.01) and hemoglobin levels (p<0.05). In addition, the percentage of quiescent HSC (LSK) was significantly increased (p=0.001) by long-term treatment with MET alone. However, the absolute number of progenitors, measured by LSK frequency or CFU-S, was not significantly altered by MET therapy. The combination of metformin and oxymetholone did not result in a significant synergistic effect on any parameter. Male animals on MET+OXM or MET alone were significantly leaner than controls at 18 months, regardless of genotype. Gene expression analysis of liver tissue from these animals showed that some of the expression changes caused by Fancd2 deletion were partially normalized by metformin treatment. Importantly, no adverse effects of the individual or combination therapies were observed, despite the long-term administration.

Involving men in cervical cancer prevention; a qualitative enquiry into male perspectives on screening and HPV vaccination in Mid-Western Uganda.

INTRODUCTION: Evidence-based preventive strategies for cervical cancer in low-resource setting have been developed, but implementation is challenged, and uptake remains low. Women and girls experience social and economic barriers to attend screening and human papillomavirus (HPV) vaccination programs. Male support has been proven successful in uptake of other reproductive healthcare services. This qualitative study with focus groups aimed to understand the perspectives of males on cervical cancer screening and HPV vaccination in Western-Uganda This knowledge could be integrated into awareness activities to increase the attendance of cervical cancer screening and HPV vaccination programs. MATERIALS AND METHODS: Focus group discussions were conducted with men aged 25 to 60 years, who were married and/or had daughters, in Kagadi district, Mid-Western Uganda. All interviews were transcribed verbatim and thematically analyzed using an inductive approach. RESULTS: Eleven focus group discussions were conducted with 67 men. Men were willing to support their wives for screening and their daughters for HPV vaccination. Misperceptions such as family planning and poor personal hygiene leading to cervical cancer, and misperception of the preventative aspect of screening and vaccination were common. Women with cervical cancer suffer from stigmatization and family problems due to loss of fertility, less marital sexual activity, domestic violence and decreased economic productivity. CONCLUSIONS: Ugandan men were willing to support cervical cancer prevention for their wives and daughters after being informed about cervical cancer. Limited knowledge among men about the risk factors and causes of cervical cancer, and about the preventative aspect of HPV vaccination and screening and their respective target groups, can limit uptake of both services. Screening and vaccination programs should actively involve men in creating awareness to increase uptake and acceptance of prevention.

Outcomes of Robot-Assisted Laparoscopic Pyeloplasty Based on Degree of Obstruction on Preoperative Tc-99 MAG-3 Renal Scintigraphy.

Objective: Management of symptomatic ureteropelvic junction (UPJ) obstruction with hydronephrosis and discordant Tc-99 mercaptoacetyltriglycine (MAG-3) renal scintigraphy is challenging. In this study we describe long-term outcomes of patients who underwent robot-assisted laparoscopic pyeloplasty for the correction of symptomatic UPJ obstruction with discordant preoperative Tc-99m MAG-3 renal scintigraphy. Methods: Patients undergoing robot-assisted laparoscopic pyeloplasty for symptomatic UPJ obstruction at a single academic center from 2009 to 2021 were retrospectively reviewed. Patients were categorized into three groups with varying degrees of obstruction based on preoperative MAG-3 imaging: Group 1: no obstruction (Lasix T1/2 clearance <10 minutes), Group 2: equivocal obstruction (Lasix T1/2 clearance 10-20 minutes), and Group 3: obstruction (Lasix T1/2 clearance >20 minutes. Pyeloplasty success was defined as resolution of symptoms and improvement/stable computed tomography (CT) imaging or MAG-3 scintigraphy. Failure was defined as persistence of symptoms with either obstruction on functional imaging, worsening hydronephrosis, or subsequent intervention. Results: A total of 125 cases were identified, with a median patient age of 35 years. Dismembered pyeloplasty technique was performed in 98.4% of cases. Median preoperative split renal function on MAG-3 scintigraphy was the only statistically significant (p = 0.003) difference in preoperative characteristics between the three groups. There were 15 postoperative complications, with a rate of Clavien-Dindo grade 3 or higher complications of 4.8%. Overall pyeloplasty success was 92.8%, with success rates of 100% (15/15) and 97% (32/33) in the no obstruction and equivocal obstruction groups, respectively. Median time to pyeloplasty failure was 20.4 months. Conclusion: Robot-assisted laparoscopic pyeloplasty is a safe and effective surgical intervention for correcting UPJ obstruction. Patients with symptoms of UPJ obstruction and discordant functional imaging studies demonstrate similar or improved success rates after pyeloplasty compared with patients with documented high-grade obstruction. Based on these findings preoperative renal scan may not be reliable in appropriate selection of candidacy for pyeloplasty.

Harvard Medical School Department of Global Health and Social Medicine COVID-19 seminar series: COVID and surgical, anesthetic and obstetric care.

On May 21, 2020, the Harvard Program in Global Surgery and Social Change (PGSSC) hosted a webinar as part of the Harvard Medical School Department of Global Health and Social Medicine's COVID-19 webinar series. The goal of PGSSC's virtual webinar was to share the experiences of surgical, anesthesia, and obstetric (SAO) providers on the frontlines of the COVID pandemic, from both high-income countries (HICs), such as the United States and the United Kingdom, as well as low- and middle-income countries (LMICs). Providers shared not only their experiences delivering SAO care during this global pandemic, but also solutions and innovations they and their colleagues developed to address these new challenges. Additionally, the seminar explored the relationship between surgery and health system strengthening and pandemic preparedness, and outlined the way forward, including a roadmap for prioritization and investment in surgical system strengthening. Throughout the discussion, other themes emerged as well, such as the definition of elective surgery and its implications during a persistent global pandemic, the safe and ethical reintroduction of surgical services, and the social inequities exposed by the stress placed on health systems by COVID-19. These proceedings document the perspectives shared by participants through their invited lectures as well as through the panel discussion at the end of the seminar.

Tobacco use and its association with HPV infection in normal uterine cervix: A study from a Sustainable Development Goals perspective.

INTRODUCTION: To achieve the Sustainable Development Goals (SDGs) target 2030, the United Nations (UN) endorsed tobacco use reduction, which is essential in decreasing unnecessary deaths caused by tobacco-induced disease. This study investigates the association between tobacco use and Human Papillomavirus (HPV) infection in clinically normal uterine cervix populations from the SDGs perspective. METHODS: This study is a 7-year cross-sectional study of a clinically normal uterine cervix population, based on negative Visual Inspection of Acetic Acid (VIA). Subjects were recruited consecutively from the medical records of several public and private health providers in Jakarta. The Statistical Product and Service Solutions (SPSS) for Windows version 20.0 were used to analyze the data. RESULTS: A total of 1397 negative VIA subjects were collected, consisting of 4.9% (69/1397) tobacco users, and 95.1% (1328/1397) non-users. HPV-DNA positive were 4.3% (3/69) in the tobacco user group and 3.7% (49/1328) in the non-user group. Statistical analysis showed unadjusted OR was 1.19 (95% CI: 0.36-3.91, p=0.778) and adjusted OR was 1.18 (95% CI: 0.36-3.89, p=0.786). High-risk HPV (hrHPV) infections of tobacco and non-tobacco users' groups were found in 2/3 and 27/49 (55.1%), respectively. CONCLUSIONS: This study showed an insignificant statistical association between tobacco use and HPV infection in normal uterine cervix. However, the proportion of hrHPV infection was higher in tobacco users than non-users. From the SDGs perspective, cervical cancer is closely related to tobacco use and poverty. Further study is needed to support this result and evaluate other co-factor role-related cervical cancer history to achieve SDGs in 2030.

Therapeutic liver repopulation by transient acetaminophen selection of gene-modified hepatocytes.

Gene therapy by integrating vectors is promising for monogenic liver diseases, especially in children where episomal vectors remain transient. However, reaching the therapeutic threshold with genome-integrating vectors is challenging. Therefore, we developed a method to expand hepatocytes bearing therapeutic transgenes. The common fever medicine acetaminophen becomes hepatotoxic via cytochrome p450 metabolism. Lentiviral vectors with transgenes linked in cis to a Cypor shRNA were administered to neonatal mice. Hepatocytes lacking the essential cofactor of Cyp enzymes, NADPH-cytochrome p450 reductase (Cypor), were selected in vivo by acetaminophen administration, replacing up to 50% of the hepatic mass. Acetaminophen treatment of the mice resulted in over 30-fold expansion of transgene-bearing hepatocytes and achieved therapeutic thresholds in hemophilia B and phenylketonuria. We conclude that therapeutically modified hepatocytes can be selected safely and efficiently in preclinical models with a transient regimen of moderately hepatotoxic acetaminophen.

Palliative care needs and preferences of female patients and their caregivers in Ethiopia: A rapid program evaluation in Addis Ababa and Sidama zone.

INTRODUCTION: In Ethiopia there is an extensive unmet need for palliative care, while the burden of non-communicable diseases and cancer is increasing. This study aimed to explore palliative care needs and preferences of patients, their caregivers, and the perspective of stakeholders on service provision in palliative programs for women, mostly affected by cervical cancer and breast cancer. METHODS: A rapid program evaluation using a qualitative study approach was conducted in three home-based palliative care programs in Addis Ababa and Yirgalem town, Ethiopia. Female patients enrolled in the programs, and their primary caregivers were interviewed on palliative care needs, preferences and service provision. We explored the views of purposely selected stakeholders on the organization of palliative care and its challenges. Audio-taped data was transcribed verbatim and translated into English and an inductive thematic analysis was applied. Descriptive analyses were used to label physical signs and symptoms using palliative outcome scale score. RESULTS: A total of 77 interviews (34 patients, 12 primary caregivers, 15 voluntary caregivers, 16 stakeholders) were conducted. The main physical complaints were moderate to severe pain (70.6%), followed by anorexia (50.0%), insomnia, nausea and vomiting (41.2%). Social interaction and daily activities were hampered by the patients' condition. Both patients and caregivers reported that programs focus most on treatment of symptoms, with limited psychosocial, emotional, spiritual and economic support. Lack of organizational structures and policy directions limit the collaboration between stakeholders and the availability of holistic home-based palliative care services. CONCLUSIONS: Although female patients and caregivers appreciated the palliative care and support provided, the existing services did not cover all needs. Pain management and all other needed supports were lacking. Multi-sectorial collaboration with active involvement of community-based structures is needed to improve quality of care and access to holistic palliative care services.

Next generation sequencing in patients with nephrolithiasis: how does it perform compared with standard urine and stone cultures?

BACKGROUND: Our aim was to compare microorganism detection between standard culture (Ctx) and next generation sequencing (NGS) in patients undergoing surgery for nephrolithiasis; we prospectively compared both urine and stone culture results using these two techniques. METHODS: We prospectively compared microorganism detection of urine and stone cultures using Ctx versus NGS in patients undergoing surgery for nephrolithiasis. We analyzed preoperative voided urine (Voided) using both Ctx and NGS. Intraoperatively, renal stone (Stone) cultures were analyzed with Ctx and NGS. The primary outcome was concordance in microorganism detection between Voided Ctx and Stone NGS, as well as between Stone Ctx and Stone NGS. RESULTS: We prospectively evaluated 84 patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of Voided Ctx predicting Stone Ctx were 66.7%, 73.7%, 54.5%, and 82.4%, respectively. Concordance of Voided Ctx microorganisms to Stone microorganisms decreased when NGS was used for the Stone compared with Ctx. The sensitivity, specificity, PPV, and NPV of Voided NGS to predict Stone Ctx microorganisms were 85.2%, 24.6%, 34.8%, and 77.8%, respectively. The concordance of Voided NGS to Stone microorganisms improved when the Stone was analyzed via NGS compared with Ctx. CONCLUSION: NGS has a higher detection rate of microorganisms than standard culture for both preoperative urine and stone cultures. Voided NGS was the most sensitive in predicting a positive Stone sample, but the specificity and PPV were, overall, low. Further correlation of NGS microorganism detection with patient outcomes will determine which clinical situations may benefit most from NGS versus standard culture in patients with urinary-tract stones.

Proliferative polyploid cells give rise to tumors via ploidy reduction.

Polyploidy is a hallmark of cancer, and closely related to chromosomal instability involved in cancer progression. Importantly, polyploid cells also exist in some normal tissues. Polyploid hepatocytes proliferate and dynamically reduce their ploidy during liver regeneration. This raises the question whether proliferating polyploids are prone to cancer via chromosome missegregation during mitosis and/or ploidy reduction. Conversely polyploids could be resistant to tumor development due to their redundant genomes. Therefore, the tumor-initiation risk of physiologic polyploidy and ploidy reduction is still unclear. Using in vivo lineage tracing we here show that polyploid hepatocytes readily form liver tumors via frequent ploidy reduction. Polyploid hepatocytes give rise to regenerative nodules with chromosome aberrations, which are enhanced by ploidy reduction. Although polyploidy should theoretically prevent tumor suppressor loss, the high frequency of ploidy reduction negates this protection. Importantly, polyploid hepatocytes that undergo multiple rounds of cell division become predominantly mononucleated and are resistant to ploidy reduction. Our results suggest that ploidy reduction is an early step in the initiation of carcinogenesis from polyploid hepatocytes.

Simulation capacity building in rural Indian hospitals: a 1-year follow-up qualitative analysis.

Introduction: The benefits of simulation-based medical training are well described. The most effective way to plant and scale simulation training in rural locations remains undescribed. We sought to plant simulation training programmes for anaesthesia emergencies in two rural Indian hospitals. Methods: Two Indian consultant anaesthetists without experience in medical simulation underwent a 3-day course at the Boston Children's Hospital's (BCH) Simulator Program. They returned to their institutions and launched simulation programmes with an airway manikin and mock patient monitor. The 1-year experience was evaluated using individual, in-depth interviews of simulation facilitators. Three staff members (responsible for facilitating medical simulations over the prior year) at two rural hospitals in India were interviewed. None attended the BCH training; instead, they received on-the-job training from the BCH-trained, consultant anaesthetist colleagues. Results: Successes included organisational adoption of simulation training with exercises 1 year after the initial BCH-training, increased interdisciplinary teamwork and improved clinical competency in managing emergencies. Barriers to effective, local implementation of simulation programmes fell into three categories: time required to run simulations, fixed and rigid roles, and variable resources. Thematic improvement requests were for standardised resources to help train simulation facilitators and demonstrate to participants a well-run simulation, in addition to context-sensitive scenarios. Conclusion: An in-person training of simulation facilitators to promote medical simulation programmes in rural hospitals produced ongoing simulation programmes 1 year later. In order to make these programmes sustainable, however, increased investment in developing simulation facilitators is required. In particular, simulation facilitators must be prepared to formally train other simulation facilitators, too.

The Macroeconomic Consequences Of Firearm-Related Fatalities In OECD Countries, 2018-30: A Value-Of-Lost-Output Analysis.

We modeled gross domestic product (GDP) losses attributable to firearm-related fatalities in each of thirty-six Organization for Economic Cooperation and Development (OECD) countries using the value-of-lost-output approach from 2018 to 2030. There are three categories of firearm-related fatalities: physical violence, self-harm, and unintentional injury. We project that the thirty-six OECD countries will lose $239.0 billion in cumulative GDP from 2018 to 2030 from firearm-related fatalities. Most of these losses ($152.5 billion) will occur as a result of fatalities in the US. In 2030 alone, the OECD countries will collectively lose $30.4 billion (0.04 percent) of their estimated annual GDP from firearm-related fatalities. The highest relative losses will occur in Mexico and the US; the lowest will occur in Japan. Firearm-related fatalities are expected to disproportionately affect the US and Mexican economies. Across the OECD, 48.5 percent of economic losses will be attributable to physical violence, 47.0 percent to self-harm, and 4.6 percent to unintentional injury. These findings provide a more complete picture of the toll of firearm-related fatalities, a global public health crisis that, without intervention, will continue to impose significant economic losses across OECD countries.

Qualitative study of yoga for Young adults in school sports.

OBJECTIVES: Distress and stress-related diseases are an increasing public health problem at schools. This qualitative study was nested in a non-randomized, controlled trial studying the effects of a 10-week yoga course as an alternative for regular school sports in two secondary schools in Germany. METHODS: We conducted a qualitative evaluation in 3 focus groups with 6 participants each. The focus groups were audio-recorded, transcribed verbatim, pseudonymised and analysed using qualitative content analysis. Furthermore open questions were asked in questionnaires. RESULTS: The analysis of the participants' interviews (mean age 19.6 ± 2.9 years, n = 10 female, n = 8 male) resulted in 4 key topics: 1. encountering yoga, 2. yoga practice, 3. effects and benefits of yoga, and 4. yoga in the school context. Yoga was very well accepted by most participants. They reported a variety of physical and psychological benefits as well as overall restorative effects. The relief of pain or other physical ailments, higher mobility and flexibility, improved posture and improved sleep were mentioned by the participants. Some participants used the new exercises and experiences (e.g. working with the breath) in their everyday life. The possibility for self-responsible action was a welcome change from the perceived pressure and heteronomy in normal (school) life. Controversial was the question of whether yoga - if it is part of school sport - should be assessed or graded, and whether it should be compulsory or voluntary. CONCLUSION: Yoga can offer both physical and psychological benefits in young adults as well as offer general regenerative effects. Yoga by sensitizing the participants to negative patterns of behaviour can encourage healthy behaviour.

Restructuring of a General Surgery Residency Program in an Epicenter of the Coronavirus Disease 2019 Pandemic: Lessons From New York City.

On March 1, 2020, the first case of coronavirus disease 2019 (COVID-19) was confirmed in New York, New York. Since then, the city has emerged as an epicenter for the ongoing pandemic in the US. To meet the anticipated demand caused by the predicted surge of patients with COVID-19, the Department of Surgery at NewYork-Presbyterian Hospital/Weill Cornell Medicine developed and executed an emergent restructuring of general surgery resident teams and educational infrastructure. The restructuring of surgical services described in this Special Communication details the methodology used to safely deploy the necessary amount of the resident workforce to support pandemic efforts while maintaining staffing for emergency surgical care, limiting unnecessary exposure of residents to infection risk, effectively placing residents in critical care units, and maintaining surgical education and board eligibility for the training program as a whole.

Comparative analysis of authorship trends in the Journal of Hand Surgery European and American volumes: A bibliometric analysis.

BACKGROUND: The purpose of this study was to better understand the authorship publishing trends in the field of hand surgery. To accomplish this, a comparative analysis was completed between the European and American volumes of the Journal of Hand Surgery (JHSE and JHSA) over the past three decades. Well-established bibliometric methods were used to examine one representative year from each of the past three decades. The focus of the study was to examine changes in author gender over time as well as to compare authorship trends across the two volumes. MATERIALS AND METHODS: All JHSA and JHSE publications from 1985, 1995, 2005, and 2015 were placed into a Microsoft Excel spreadsheet. Data was collected for each publication including the gender of first and corresponding authors, corresponding author position, corresponding author country of origin, number of credited institutions, authors, printed pages, and references. Countries were grouped by regions. RESULTS: A total of 450 and 763 manuscripts from JHSE and JHSA, respectively, met inclusion criteria. JHSE and JHSA both showed increases in most variables analyzed over time. Both journals showed an increase in female first and corresponding authors. JHSE and JHSA displayed a rise in collaboration between institutions and countries. CONCLUSIONS: Both JHSE and JHSA display increasing female inclusion in the hand surgery literature, which has traditionally been a male dominated field. The observed increase in collaboration between institutions and countries is likely linked to advances in technology that allow sharing of information more conveniently and reliably than was previously possible. As further advances are made socially and technologically, hopefully these trends will continue, leading to faster and higher quality research being generated in the field of hand surgery.

Innovative financing to fund surgical systems and expand surgical care in low-income and middle-income countries.

Strong surgical systems are necessary to prevent premature death and avoidable disability from surgical conditions. The epidemiological transition, which has led to a rising burden of non-communicable diseases and injuries worldwide, will increase the demand for surgical assessment and care as a definitive healthcare intervention. Yet, 5 billion people lack access to timely, affordable and safe surgical and anaesthesia care, with the unmet demand affecting predominantly low-income and middle-income countries (LMICs). Rapid surgical care scale-up is required in LMICs to strengthen health system capabilities, but adequate financing for this expansion is lacking. This article explores the critical role of innovative financing in scaling up surgical care in LMICs. We locate surgical system financing by using a modified fiscal space analysis. Through an analysis of published studies and case studies on recent trends in the financing of global health systems, we provide a conceptual framework that could assist policy-makers in health systems to develop innovative financing strategies to mobilise additional investments for scale-up of surgical care in LMICs. This is the first time such an analysis has been applied to the funding of surgical care. Innovative financing in global surgery is an untapped potential funding source for expanding fiscal space for health systems and financing scale-up of surgical care in LMICs.

Safety and efficiency of gasless laparoscopy: a systematic review protocol.

BACKGROUND: Gasless laparoscopy, developed in the early 1990s, was a means to minimize the clinical and financial challenges of pneumoperitoneum and general anaesthesia. It has been used in a variety of procedures such as in general surgery and gynecology procedures including diagnostic laparoscopy. There has been increasing evidence of the utility of gasless laparoscopy in resource limited settings where diagnostic imaging is not available. In addition, it may help save costs for hospitals. The aim of this study is to conduct a systematic review of the available evidence surrounding the safety and efficiency of gasless laparoscopy compared to conventional laparoscopy and open techniques and to analyze the benefits that gasless laparoscopy has for low resource setting hospitals. METHODS: This protocol is developed by following the Preferred Reporting Items for Systematic review and Meta-Analysis-Protocols (PRISMA-P). The PRISMA statement guidelines and flowchart will be used to conduct the study itself. MEDLINE (Ovid), Embase, Web of Science, Cochrane Central, and Global Index Medicus (WHO) will be searched and the National Institutes of Health Clinical Trials database. The articles that will be found will be pooled into Covidence article manager software where all the records will be screened for eligibility and duplicates removed. A data extraction spreadsheet will be developed based on variables of interest set a priori. Reviewers will then screen all included studies based on the eligibility criteria. The GRADE tool will be used to assess the quality of the studies and the risk of bias in all the studies will be assessed using the Cochrane Risk assessment tool. The RoB II tool will assed the risk of bias in randomized control studies and the ROBINS I will be used for the non-randomized studies. DISCUSSION: This study will be a comprehensive review on all published articles found using this search strategy on the safety and efficiency of the use of gasless laparoscopy. The systematic review outcomes will include safety and efficiency of gasless laparoscopy compared to the use of conventional laparoscopy or laparotomy. TRIAL REGISTRATION: The study has been registered in PROSPERO under registration number: CRD42017078338.