A pair of readers of bivalent chromatin mediate formation of Polycomb-based "memory of cold" in plants.

The Polycomb-group chromatin modifiers play important roles to repress or switch off gene expression in plants and animals. How the active chromatin state is switched to a Polycomb-repressed state is unclear. In Arabidopsis, prolonged cold induces the switching of the highly active chromatin state at the potent floral repressor FLC to a Polycomb-repressed state, which is epigenetically maintained when temperature rises to confer "cold memory," enabling plants to flower in spring. We report that the cis-acting cold memory element (CME) region at FLC bears bivalent marks of active histone H3K4me3 and repressive H3K27me3 that are read and interpreted by an assembly of bivalent chromatin readers to drive cold-induced switching of the FLC chromatin state. In response to cold, the 47-bp CME and its associated bivalent chromatin feature drive the switching of active chromatin state at a recombinant gene to a Polycomb-repressed domain, conferring cold memory. We reveal a paradigm for environment-induced chromatin-state switching at bivalent loci in plants.

Neurodevelopmental and synaptic defects in DNAJC6 parkinsonism, amenable to gene therapy.

DNAJC6 encodes auxilin, a co-chaperone protein involved in clathrin-mediated endocytosis (CME) at the presynaptic terminal. Biallelic mutations in DNAJC6 cause a complex, early-onset neurodegenerative disorder characterized by rapidly progressive parkinsonism-dystonia in childhood. The disease is commonly associated with additional neurodevelopmental, neurological and neuropsychiatric features. Currently, there are no disease-modifying treatments for this condition, resulting in significant morbidity and risk of premature mortality. To investigate the underlying disease mechanisms in childhood-onset DNAJC6 parkinsonism, we generated induced pluripotent stem cells (iPSC) from three patients harbouring pathogenic loss-of-function DNAJC6 mutations and subsequently developed a midbrain dopaminergic neuronal model of disease. When compared to age-matched and CRISPR-corrected isogenic controls, the neuronal cell model revealed disease-specific auxilin deficiency as well as disturbance of synaptic vesicle recycling and homeostasis. We also observed neurodevelopmental dysregulation affecting ventral midbrain patterning and neuronal maturation. To explore the feasibility of a viral vector-mediated gene therapy approach, iPSC-derived neuronal cultures were treated with lentiviral DNAJC6 gene transfer, which restored auxilin expression and rescued CME. Our patient-derived neuronal model provides deeper insights into the molecular mechanisms of auxilin deficiency as well as a robust platform for the development of targeted precision therapy approaches.

Guanylate-binding protein 1 inhibits Hantaan virus infection by restricting virus entry.

Hantaan virus (HTNV) infection can cause hemorrhagic fever with renal syndrome (HFRS) in humans, and currently, there are no long-standing protective vaccines or specific antivirals available. Guanylate-binding protein 1 (GBP1) is an interferon-stimulated gene that defends against various pathogen infections. However, the function of GBP1 in HTNV infection remains unknown. Here, we describe how GBP1 prevents HTNV infection by obstructing virus entry. We found that HTNV infection induced GBP1 expression and that overexpression of GBP1 inhibited HTNV infection, while knockout of GBP1 had the opposite effect. Interestingly, GBP1 did not affect interferon (IFN) signaling during HTNV infection. Instead, GBP1 prevented HTNV from entering cells through clathrin-mediated endocytosis (CME). We also discovered that GBP1 specifically interacted with actin but not dynamin 2 (DNM2) and made it difficult for DNM2 to be recruited by actin, which may account for the suppression of CME during HTNV infection. These findings establish an antiviral role for GBP1 in inhibiting HTNV infection and help us better understand how GBP1 regulates HTNV entry and could potentially aid in developing treatments for this virus.

The diverse dependence of galectin-1 and -8 on multivalency for the modulation of FGFR1 endocytosis.

Fibroblast growth factor receptor 1 (FGFR1) is a N-glycosylated cell surface receptor tyrosine kinase, which upon recognition of specific extracellular ligands, fibroblast growth factors (FGFs), initiates an intracellular signaling. FGFR1 signaling ensures homeostasis of cells by fine-tuning essential cellular processes, like differentiation, division, motility and death. FGFR1 activity is coordinated at multiple steps and unbalanced FGFR1 signaling contributes to developmental diseases and cancers. One of the crucial control mechanisms over FGFR1 signaling is receptor endocytosis, which allows for rapid targeting of FGF-activated FGFR1 to lysosomes for degradation and the signal termination. We have recently demonstrated that N-glycans of FGFR1 are recognized by a precise set of extracellular galectins, secreted and intracellular multivalent lectins implicated in a plethora of cellular processes and altered in immune responses and cancers. Specific galectins trigger FGFR1 clustering, resulting in activation of the receptor and in initiation of intracellular signaling cascades that shape the cell physiology. Although some of galectin family members emerged recently as key players in the clathrin-independent endocytosis of specific cargoes, their impact on endocytosis of FGFR1 was largely unknown.Here we assessed the contribution of extracellular galectins to the cellular uptake of FGFR1. We demonstrate that only galectin-1 induces internalization of FGFR1, whereas the majority of galectins predominantly inhibit endocytosis of the receptor. We focused on three representative galectins: galectin-1, -7 and -8 and we demonstrate that although all these galectins directly activate FGFR1 by the receptor crosslinking mechanism, they exert different effects on FGFR1 endocytosis. Galectin-1-mediated internalization of FGFR1 doesn't require galectin-1 multivalency and occurs via clathrin-mediated endocytosis, resembling in this way the uptake of FGF/FGFR1 complex. In contrast galectin-7 and -8 impede FGFR1 endocytosis, causing stabilization of the receptor on the cell surface and prolonged propagation of the signals. Furthermore, using protein engineering approaches we demonstrate that it is possible to modulate or even fully reverse the endocytic potential of galectins.

Laparoscopic right hemicolectomy: a SICE (Società Italiana di Chirurgia Endoscopica e Nuove tecnologie) network prospective study on the approach to right colon lymphadenectomy in Italy: is there a standard?-CoDIG 2 (ColonDx Italian Group).

BACKGROUND: Colon cancer is a disease with a worldwide spread. Surgery is the best option for the treatment of advanced colon cancer, but some aspects are still debated, such as the extent of lymphadenectomy. In Japanese guidelines, the gold standard was D3 dissection to remove the central lymph nodes (203, 213, and 223), but in 2009, Hoenberger et al. introduced the concept of complete mesocolic excision, in which surgical dissection follows the embryological planes to remove the mesentery entirely to prevent leakage of cancer cells and collect more lymph nodes. Our study describes how lymphadenectomy is currently performed in major Italian centers with an unclear indication on the type of lymphadenectomy that should be performed during right hemicolectomy (RH). METHODS: CoDIG 2 is an observational multicenter national study that involves 76 Italian general surgery wards highly specialized in colorectal surgery. Each center was asked not to modify their usual surgical and clinical practices. The aim of the study was to assess the preference of Italian surgeons on the type of lymphadenectomy to perform during RH and the rise of any new trends or modifications in habits compared to the findings of the CoDIG 1 study conducted 4 years ago. RESULTS: A total of 788 patients were enrolled. The most commonly used surgical technique was laparoscopic (82.1%) with intracorporeal (73.4%), side-to-side (98.7%), or isoperistaltic (96.0%) anastomosis. The lymph nodes at the origin of the vessels were harvested in an inferior number of cases (203, 213, and 223: 42.4%, 31.1%, and 20.3%, respectively). A comparison between CoDIG 1 and CoDIG 2 showed a stable trend in surgical techniques and complications, with an increase in the robotic approach (7.7% vs. 12.3%). CONCLUSIONS: This analysis shows how lymphadenectomy is performed in Italy to achieve oncological outcomes in RH, although the technique to achieve a higher lymph node count has not yet been standardized. Trial registration (ClinicalTrials.gov) ID: NCT05943951.

Peripapillary hyperreflective ovoid mass-like structures with cystoid macular edema: a case report.

BACKGROUND: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are newly characterized lesions wedged around the optic discs, which used to be misdiagnosed. Better understanding and identifying PHOMS are important for monitoring the condition of optic nerve. CASE PRESENTATION: A young female presented to the ophthalmic clinic with blurred vision of both eyes. Protrusions resembling "C-shaped donut" were found circling the optic discs bilaterally. These lesions were homogenous hyperreflective on OCT, while they were also hypoautofluorescent and hypoechogenic. Meanwhile, cystoid macular edema (CME) was also identified in both eyes. The patient was then diagnosed as PHOMS with CME. A short-term glucocorticoids therapy was prescribed systemically. The logMAR best-corrected visual acuity (BCVA) of both eyes reached 0.0 in 4 months with recovery of CME, while the PHOMS remained. CONCLUSIONS: There is currently no report on PHOMS with CME. More attentions should be paid to PHOMS, for they are potential biomarkers for axoplasmic stasis involved in different diseases of the optic nerve.

Promises, Pitfalls, and Clinical Applications of Artificial Intelligence in Pediatrics.

Artificial intelligence (AI) broadly describes a branch of computer science focused on developing machines capable of performing tasks typically associated with human intelligence. Those who connect AI with the world of science fiction may meet its growing rise with hesitancy or outright skepticism. However, AI is becoming increasingly pervasive in our society, from algorithms helping to sift through airline fares to substituting words in emails and SMS text messages based on user choices. Data collection is ongoing and is being leveraged by software platforms to analyze patterns and make predictions across multiple industries. Health care is gradually becoming part of this technological transformation, as advancements in computational power and storage converge with the rapid expansion of digitized medical information. Given the growing and inevitable integration of AI into health care systems, it is our viewpoint that pediatricians urgently require training and orientation to the uses, promises, and pitfalls of AI in medicine. AI is unlikely to solve the full array of complex challenges confronting pediatricians today; however, if used responsibly, it holds great potential to improve many aspects of care for providers, children, and families. Our aim in this viewpoint is to provide clinicians with a targeted introduction to the field of AI in pediatrics, including key promises, pitfalls, and clinical applications, so they can play a more active role in shaping the future impact of AI in medicine.

An overview of global CME/CPD systems.

PURPOSE: Engagement in CME/CPD has a positive impact on healthcare professionals' (HCPs) knowledge, skills, and performance, and on patient outcomes, therefore it is critical to better understand the components of CME/CPD systems that foster engagement, high-quality education, and impact. METHODS: An assessment of CME/CPD systems was conducted using a mixed-methods approach that included interviews with in-country subject matter experts and qualitative and quantitative data from practicing in-country physicians. RESULTS: Results demonstrate areas of consistency in CME/CPD systems across world regions that included: types of educational providers; types of credit; educational formats; self-tracking of participation; high-degree of compliance when education is mandatory; overall satisfaction with available education; strong support for interprofessional education; and lack of alignment or evaluation of engagement in education with population health outcomes. Areas of variation included: whether engagement in education is required as a condition to practice medicine; whether regulations are uniformly applied; if mechanisms to ensure independence existed; and physician perceptions of independence. CONCLUSION: Results of this assessment maybe used by a variety of different stakeholders to assess how well country-level CME/CPD systems are meeting the needs of practicing physicians and determine what, if any, changes might need to be implemented to improve outcomes.

CME providers' experiences and practices in Pakistan: a case study.

BACKGROUND: Pakistan has made numerous attempts to establish and implement a national mandatory CME program which currently do not exist. The purpose of this study is to explore the views of major CME providers in order to identify possible strengths and weaknesses in the current program, and offer evidence-based recommendations to help further enhance the national CME program in Pakistan. METHODS: An exploratory study design using a case study approach through in depth interviews was conducted to examine CME providers' experiences and perceptions. The study was conducted in Pakistan between August and November 2019 with CME providers from Sindh, Punjab, the North-West Frontier Province, and the Federal Capital Territory. Thirty-six providers recognised by the Pakistan Medical and Dental Council who were involved in providing CME activities at the national level and whose contact information was publicly available on their websites, were selected for the study. Of the 36 providers invited, 22 participated in this study. RESULTS: The results generated several organising themes grouped into three major themes: (1) CME current practices, (2) CME past experiences, and (3) Future developments. CONCLUSION: Participants recommended needs-based educational activities for physicians, a well-structured central regulatory CME body collaborating with existing providers, involving experienced providers for rural CME, accrediting diverse local providers, limiting commercial entities' role, and implementing CME with proper preparation and a phased approach.

Reducing patients' rate of frequent attendance through a training intervention for physicians.

BACKGROUND: Frequent attendance is a common issue for primary care health centres. The phenomenon affects the quality of care, increases doctors' workloads and can lead to burnout.This study presents the results of an educational intervention for primary care physicians, aimed at helping them to decrease the prevalence rate of excessive attendance by patients at their centres. METHODS: A training programme was carried out for 11 primary care doctors in Barcelona who had patient lists totalling 20,064 patients. The goal of the training was to provide the participating physicians with techniques to curb frequent attendance. Additionally, the programme sought to offer them strategies to prevent professional burnout and tools to better organize their everyday medical practice. The study used a quasi-experimental design for an evaluation of an educational intervention, featuring a pre-test assessment (before the training programme) and a post-test assessment (after the training programme), as well as comparison with a control group that did not undergo the training. The study assessed the effects of the programme on the rates of frequent attendance of patients served by the participating physicians. These rates were compared with those registered by the patients seen by the control group physicians over the same period. RESULTS: Among the group of physicians who received the training, the mean prevalence of patients who qualified as frequent attenders decreased from 22% prior to the training programme to 8% after completion of the programme. In other words, 14% of patients (2,809) limited the frequency of their visits to primary care physicians after their physicians had completed the training programme. Meanwhile, the study recorded an average decrease of 3.1 visits per year by the patients of the physicians who had undergone the training. Statistically significant differences between this group and the control group were observed. CONCLUSIONS: The educational intervention proved effective at helping primary care physicians to decrease their patients' rates of frequent attendance. It also contributes to the impact research of continuing education on doctors and their patients. We need to increase primary care spending from the current 14% to the 25%, to address this problem, among others.

Laparoscopic D3 right hemicolectomy with intracorporeal anastomosis.

Complete mesocolic excision (CME) with D3 lymphadenectomy for colon cancer has been shown to improve overall as well as disease-free survival compared to conventional right hemicolectomy. Performing a laparoscopic CME/D3 right hemicolectomy with intracorporeal anastomosis (ICA) can be technically demanding even for experienced operators. Here, we present a systematic, standardized approach to the surgery.

Surgical efficacy and learning curves of laparoscopic complete mesocolic excision with intracorporeal anastomosis for right-sided colon cancer: A retrospective two-center cohort study.

BACKGROUND: There is a potential benefit on long-term outcomes following complete mesocolic excision (CME) for right-sided colon cancer when compared to conventional colectomy. This study aims to analyze the learning curve and short-term outcomes of laparoscopic CME with intracorporeal anastomosis (ICA) for right-sided colon cancer in the hands of experienced colorectal surgeons. METHODS: A two-center cohort study of consecutive patients undergoing right-sided colectomy from September 2021 to May 2022 at two tertiary colorectal centers in Denmark. Learning curves of surgical time were estimated using a cumulative sum analysis (CUSUM). RESULTS: A total of 61 patients were included. According to the CUSUM analysis, 32 cases were needed to obtain a peak in operative time, resulting in a decrease in time consumption (group 1/learning phase: 217.2 min [SD 53.6] and group 2/plateau phase 191.6 min [SD 45.1], p = 0.05). There was a nonsignificant reduction in the rates of severe surgical complications (Clavien-Dindo > 3) (13% vs. 7%, p = 0.67) between the two groups, while the length of hospital stay remained constant (median 3.0 days, interquartile range, IQR [2.0; 4.0]). CONCLUSION: The learning curve of laparoscopic CME with ICA for right-sided colon cancer demonstrated that 32 cases were needed to obtain a plateau phase expressed by operative time.

Long-term oncologic outcome of D3 lymph node dissection for clinical stage 2/3 right-sided colon cancer.

PURPOSE: To investigate oncologic outcomes including overall survival and disease-free survival depending on the extent of lymphadenectomy (D3 versus D2) by comparing D3 and D2 lymphadenectomy in patients with clinical stage 2/3 right colon cancer. METHODS: Consecutive series of patients who underwent radical resection for right colon cancer at our three hospitals between January 2015 and June 2018 were retrospectively analyzed. Study cohorts were divided into two groups: D3 group and D2 group. Oncologic, pathologic, and perioperative outcomes of the two groups were compared. RESULTS: A total of 295 patients (167 in the D2 group and 128 in the D3 group) were included in this study. Patients' characteristics showed no significant difference between the two groups. The median number of harvested lymph nodes was significantly higher in the D3 group than in the D2 group. The rate of complications was not significantly different between the two groups except for chyle leakage, which was more frequent in the D3 group. Five-year disease-free survival was 90.2% (95% CI: 84.8-95.9%) in the D3 group, which was significantly (p = 0.028) higher than that (80.5%, 95% CI: 74-87.5%) in the D2 group. There was no significant difference in overall survival between the two groups. CONCLUSION: Our results indicate that D3 lymphadenectomy is associated with more favorable 5-year disease-free survival than D2 lymphadenectomy for patients with stage 2/3 right-sided colon cancer. D3 lymphadenectomy might improve oncologic outcomes in consideration of the recurrence rate.

The mesocolic apical fragment in complete mesocolic excision colectomies: Should it be analysed separately? A proof-of-concept study.

AIM: The aim of this work is to describe a protocol and assess the feasibility of harvesting and analysing the mesocolic apical fragment (MAF) for the presence of central lymph node (LN) metastasis and extra lymphatic free tumour cells in a random subgroup extracted from a cohort of complete mesocolic excision colectomies with central vascular ligation. METHOD: Forty-seven patients diagnosed with colorectal cancer were included. A 2/2 cm pyramid of tissue was cut around the central tie and sent for pathological examination. The MAF was sectioned into 16 slices. High-definition images were taken from the slices which were merged into a panoramic three-dimensional image of the MAF. The distribution of LNs in the MAF was quantified. Immunohistochemistry staining for cytokeratin 14 was used to identify isolated tumour cells and micrometastases in the extranodal tissue. RESULTS: No tumoural cells migrating through the apical zone, outside of the LNs, were identified. Margins of resection, mesocolic tissue and LNs were all negative in the subgroup of ultrastaged MAFs. The number of examined central LNs varied between 0 and 24, with positive MAF LNs being identified only in pN2 stages. The rate of positive apical LNs in our cohort was 4.2% (n = 2). CONCLUSIONS: The MAF can be easily extracted from standard specimens, allowing for accurate analysis of lymphatic and extra-nodal tumour cells on the central resection margins, in central LNs and in the apical mesocolic tissue. Future research on larger cohorts is required to establish if analysing the MAF has an impact on patient staging, prognosis and management.

Surgical and oncological outcomes of laparoscopic right hemicolectomy (D3 + CME) for colon cancer: A prospective single-center cohort study.

BACKGROUND: Complete mesocolic excision (CME) or D3 lymphadenectomy led to survival benefits for locally advanced right colon cancer, but with vague definitions in anatomy and debated surgical hazard in clinic. Aiming to achieve a precise definition of it in anatomy, we proposed laparoscopic right hemicolectomy (D3 + CME) as a novel procedure for colon cancer. However, the surgical and oncological results of this procedure in clinic were uncertain. METHODS: We performed a cohort study involving prospective data collected from a single-center in China. Data from all patients who underwent right hemicolectomy between January 2014 and December 2018 were included. We compared the surgical and oncological outcomes between D3 + CME and conventional CME. RESULTS: After implementation of exclusion criteria, a total of 442 patients were included. D3 + CME group performed better in lymph nodes harvested (25.0 [17.0, 33.8] vs. 18.0 [14.0, 25.0], P < 0.001) and the proportion of intraoperative blood loss ≥ 50 mL (31.7% vs. 51.8%, P < 0.001); no significant difference was observed in the complication rates between two groups. Kaplan-Meier analysis demonstrated that a better cumulative 5-year disease-free survival (91.3% vs. 82.2%, P = 0.026) and a better cumulative 5-year overall survival (95.2% vs. 86.1%, P = 0.012) were obtained in the D3 + CME group. Multivariate COX regression revealed that D3 + CME was an independent protective factor for disease-free survival (P = 0.026). CONCLUSION: D3 + CME could improve surgical and oncological outcomes simultaneously for right colon cancer compared to conventional CME. Large-scale randomized controlled trials were further required to confirm this conclusion, if possible.

Tackling climate change and health inequalities in primary care.

The Climate Emergency is now widely accepted as the biggest public health crisis facing humanity. Previous research has highlighted how social and health inequalities shape the health impacts of climate change in the UK, but there has been little attention to the role of general practice in deprived areas. This Brief Report summarises a roundtable discussion of Scottish 'Deep End' GPs - family doctors working in the most socio-economically deprived areas - which took place weeks before the 26th UN Climate Change Conference (COP26), held in Glasgow in November 2021. The report highlights the need for urgent action to make general practice more sustainable, including recommendations for community engagement, (de)prescribing, medical education, digital inclusion, and investment in premises and capacity building.

Refractory post-surgical cystoid macular edema managed following suprachoroidal microcatheterization and delivery of triamcinolone.

BACKGROUND: Post-surgical macular edema (ME) is a common cause of prolonged visual impairment. Here we report on the feasibility and clinical outcomes from the use of a novel suprachoroidal microcatheter to treat post-surgical chronic ME by the posterior suprachoroidal placement of a triamcinolone acetonide (TA) suspension. METHODS: Two patients were catheterized with the Oxulumis suprachoroidal delivery system on two separate occasions starting 5 and 10 mm posterior to the limbus. The catheter only remains in the suprachoroidal space for the time of the drug administration. Visual acuity and spectral domain optical coherence tomography (SD-OCT) changes were followed over several weeks to months to determine the duration of ME resolution. RESULTS: Suprachoroidal microcatheterization for posterior delivery of triamcinolone was possible in all attempts using the illuminated Oxulumis catheter. No reflux, scleral or choroidal trauma was observed. There was no intraocular pressure rise during the follow-up period. The triamcinolone deposit was visible on infrared imaging and on SD-OCT a choroidal elevation was visible. Both progressively disappeared over time. A rapid resolution of ME associated with improved vision was observed following each injection for 3 to 7 months with a TA dose of 2.4 mg or 4 mg. CONCLUSIONS: In these patients with poorly responsive ME, posterior suprachoroidal TA led to a visible suprachoroidal drug deposit and prolonged visual improvement. The Oxulumis microcatheterization device performed as expected and was not associated with any complications.

Treatment strategy for BVO-ME based on long-term outcomes correlating retinal structure by OCT image and visual acuity.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (VEGF) is a mainstream treatment for reducing ME secondary to BRVO (BVO-ME). Regrettably, most reports of intravitreal anti-VEGF for BVO-ME have disclosed only short-term outcomes. Here, we characterized long-term indicators for the visual prognosis of patients with BVO-ME, including the correlation between retinal structure by OCT and visual acuity. METHODS: Patients with BVO-ME were retrospectively recruited based on clinical records in Kansai Medical University Hospital from June 2012 to March 2022. This study enrolled patients with vision loss who received intravitreal injection of anti-VEGF for BVO-ME. Inclusion criteria were that patients received intravitreal injection of anti-VEGF as their first treatment and were followed for at least 36 months. Exclusion criteria were those patients with ocular disease other than BRVO or who had been previously treated for BVO-ME. Patients were divided into two groups according to BCVA at the final visit: Group A (≥ 0.7) and Group B (< 0.7). RESULTS: Forty-seven eyes from 45 patients were assessed. The mean follow-up period from initial to final visit was 64.38 ± 15.07 (range, 38-100) months. BCVA in Group A (n = 32) was significantly greater than in Group B (n = 15) at all timepoints. The ratio that the number of eyes which the EZ band and the foveal bulge were intact in Group A was higher than in Group B (p = 0.0004 and p = 0.0002, respectively). The ratio that the number of eyes which recurrence SRD was observed by the final visit in Group A was lower than in Group B (p = 0.0485). CONCLUSIONS: The integrity of the EZ band and an intact foveal bulge were significant predictors for visual acuity. In contrast, recurrent SRD led to poor visual acuity in the long term, even if BCVA was good in the short term.

Evaluation of practice change following SAFE obstetric courses in Tanzania: a prospective cohort study.

Anaesthesia has been shown to contribute disproportionately to maternal mortality in low-resource settings. This figure exceeds 500 per 100,000 live births in Tanzania, where anaesthesia is mainly provided by non-physician anaesthetists, many of whom are working as independent practitioners in rural areas without any support or opportunity for continuous medical education. The three-day Safer Anaesthesia from Education (SAFE) course was developed to address this gap by providing in-service training in obstetric anaesthesia to improve patient safety. Two obstetric SAFE courses with refresher training were delivered to 75 non-physician anaesthetists in the Mbeya region of Tanzania between August 2019 and July 2020. To evaluate translation of knowledge into practice, we conducted direct observation of the SAFE obstetric participants at their workplace in five facilities using a binary checklist of expected behaviours, to assess the peri-operative management of patients undergoing caesarean deliveries. The observations were conducted over a 2-week period at pre, immediately post, 6-month and 12-month post-SAFE obstetric training. A total of 320 cases completed by 35 participants were observed. Significant improvements in behaviours, sustained at 12 months after training included: pre-operative assessment of patients (32% (pre-training) to 88% (12 months after training), p < 0.001); checking for functioning suction (73% to 85%, p = 0.003); using aseptic spinal technique (67% to 100%, p < 0.001); timely administration of prophylactic antibiotics (66% to 95%, p < 0.001); and checking spinal block adequacy (32% to 71%, p < 0.001). Our study has demonstrated positive sustained changes in the clinical practice amongst non-physician anaesthetists as a result of SAFE obstetric training. The findings can be used to guide development of a checklist specific for anaesthesia for caesarean section to improve the quality of care for patients in low-resource settings.

Robot-assisted versus laparoscopic short- and long-term outcomes in complete mesocolic excision for right-sided colonic cancer: a systematic review and meta-analysis.

BACKGROUND: Complete mesocolic excision (CME) surgery is increasingly implemented for the resection of right-sided colonic cancer, possibly resulting in improved 5-year overall and disease-free survival compared to non-CME surgery. However, it is not clear what surgical platform should be used. The aim of this study was to compare the following outcomes between robot-assisted and laparoscopic CME-surgery for right-sided colonic cancer: (i) short-term clinical outcomes, (ii) pathological specimen quality, and (iii) long-term oncological outcomes. METHODS: Medline, Embase, and Cochrane Database of Systematic Reviews were searched from inception until August 2021. Pooled proportions were calculated by applying the inverse variance method. Heterogeneity was explored by I-square and supplemented by sensitivity- and meta-regression analyses. The risk of bias was evaluated by either MINORS or Cochrane's risk-of-bias tool (RoB 2). RESULTS: Fifty-five studies with 5.357 patients (740 robot-assisted and 4617 laparoscopic) were included in the meta-analysis. Overall postoperative morbidity was 17% [95% CI (14-20%)] in the robot-assisted group and 13% [95%CI (12-13%)] in the laparoscopic group. Robot-assisted CME was associated with a shorter hospital stay, lower intraoperative blood loss, a higher amount of harvested lymph nodes, and better 3-year oerall and disease-free survival. MINORS and RoB2 indicated a serious risk of bias across studies included. CONCLUSIONS: This review which includes predominantly non-randomized studies suggests a possible advantage of the robot-assisted CME compared with a laparoscopic technique for several short-term outcomes.