Enhancer-promoter specificity in gene transcription: molecular mechanisms and disease associations.

Although often located at a distance from their target gene promoters, enhancers are the primary genomic determinants of temporal and spatial transcriptional specificity in metazoans. Since the discovery of the first enhancer element in simian virus 40, there has been substantial interest in unraveling the mechanism(s) by which enhancers communicate with their partner promoters to ensure proper gene expression. These research efforts have benefited considerably from the application of increasingly sophisticated sequencing- and imaging-based approaches in conjunction with innovative (epi)genome-editing technologies; however, despite various proposed models, the principles of enhancer-promoter interaction have still not been fully elucidated. In this review, we provide an overview of recent progress in the eukaryotic gene transcription field pertaining to enhancer-promoter specificity. A better understanding of the mechanistic basis of lineage- and context-dependent enhancer-promoter engagement, along with the continued identification of functional enhancers, will provide key insights into the spatiotemporal control of gene expression that can reveal therapeutic opportunities for a range of enhancer-related diseases.

Does the angle of trocar insertion affect the fascial defect caused? A porcine model.

INTRODUCTION: With an incidence of 0-5.2%, trocar site hernias frequently occur following laparoscopy. It is unclear to what extent the angle of trocar insertion affects the size of the fascial defect caused. Hence, we performed a porcine model. METHODS: In October 2022, a total of five female pigs were euthanized. In alternating order, three bladeless and two bladed conical 12-mm trocars were inserted at an angle of 45° on each side for 60 min twice each pig. For this purpose, an epoxy resin handmade cuboid with a central channel that runs at an angle of 45° was used. Subsequently, photo imaging and defect size measurement took place. The results were compared with those of our previously conducted and published porcine model, in which the trocars were inserted at an angle of 90°. Effects of trocar type (bladed vs. bladeless) and angle on defect size were analyzed using a mixed model regression analysis. RESULTS: The bladeless trocars caused statistically significant smaller defects at the fascia than the bladed (23.4 (SD = 16.9) mm2 vs. 41.3 (SD = 14.8) mm2, p < 0.001). The bladeless VersaOne trocar caused the smallest defect of 16.0 (SD = 6.1) mm2. The bladed VersaOne trocar caused the largest defect of 47.7 (SD = 10.5) mm2. The defect size of the trocars used at a 45° angle averaged 30.5 (SD = 18.3) mm2. The defect size of trocars used at a 90° angle was significantly larger, averaging 58.3 (SD = 20.2) mm2 (p = 0.007). CONCLUSION: When conical 12-mm trocars are inserted at a 45° angle, especially bladeless ones, they appear to cause small fascial defects compared with insertion at a 90° angle. This might lead also to a lower rate of trocar hernias. Bladeless trocars might cause smaller fascial defects than bladed trocars.

Healthcare-associated infections among neonates and children in Pakistan: findings and the implications from a point prevalence survey.

BACKGROUND: Healthcare-associated infections (HAIs) increase morbidity, mortality and costs. The overall prevalence of HAIs is greater in low- and middle-income countries due to poor resources and infrastructure, with the incidence of HAIs greater among neonates and children. There is a need to understand the current situation in Pakistan including key drivers to improve future care. METHODS: Point prevalence survey (PPS) of HAIs in the children's wards of 19 public sector secondary- and tertiary-care hospitals of Pakistan and associated key drivers. RESULTS: A total of 1147 children were included in the PPS. 35.7% were neonates with 32.8% aged >1-5 years. 35.2% were admitted to the intensive care units (ICUs). Peripheral, central venous and urinary catheters were present in 48%, 2.9% and 5.6% of the patients, respectively. A total of 161 HAIs from various pathogens were observed in 153 cases, giving a prevalence of 13.3%. The majority of HAIs were caused by Staphylococcus aureus (31.7%) followed by Klebsiella pneumoniae (22.9%) and Escherichia coli (17.4%). Bloodstream infections were identified in 42 cases followed by lower-respiratory-tract infections in 35. Increased length of hospital stays and being admitted to the ICU, 'rapidly fatal' patients under the McCabe and Jackson criteria, central and peripheral catheterization, and invasive mechanical ventilation were, associated with higher HAIs (P<0.001). 99.7% of HAI patients fully recovered and were discharged from the hospital. CONCLUSION: There is a high prevalence of HAIs among neonates and children admitted to health facilities in Pakistan. Infection prevention and control measures should be implemented to help prevent future HAIs.

The assessment of haematologic and serum chemistry parameters in canine pyometra: a systematic review and meta-analysis.

OBJECTIVES: Pyometra is common in non-spayed adult female dogs requiring early diagnosis and treatment to increase the survival rate. The diagnosis of pyometra is mainly based on clinical examination and anamnesis. Radiography, ultrasonography and laboratory analyses are recommended to support a diagnosis. The aim of this study was to assess blood parameters associated with pyometra by performing a systematic review and meta-analysis. MATERIALS AND METHODS: The review was conducted in accordance with PRISMA guidelines. A search of three databases (PubMed, Google Scholar and CAB abstracts) was performed in July 2022. Studies providing information about laboratory parameters for both the pyometra group and healthy control group dogs were eligible for inclusion. Data extraction included the first author's name, publication year, country, number of participants in both groups, mean values of selected studies, standard deviation values, and blood parameters. The risk of bias for each study was evaluated, and a random-effects meta-analysis was performed. RESULTS: We included 44 studies which investigated 12 blood parameters. High heterogeneity was detected in all parameters in these meta-analyses. The following blood parameters were increased in dogs with pyometra: white blood cell (mean=27.75×109 L-1 , mean difference (MD)=17.16, 95% confidence interval (CI) 14.85 to 19.47), monocytes (mean=2.06×1012 /L, MD=1.37, 95% CI 0.99 to 1.74), blood urea nitrogen (mean=41.42 mg/dL MD=18.06, 95% CI 12.26 to 23.85), alkaline phosphatase (mean=212.78 IU/L, MD=137.51, 95% CI 81.81 to 88.62), and aspartate aminotransferase (mean=48.31 IU/L, MD=16.96, 95% CI 10.61 to 23.30). The following parameters were reduced: red blood cell (mean=5.42 1012 /L, MD=-1.37, 95% CI -1.68 to -1.05), haemoglobin (mean=121.20 g/L, MD=-30.57, 95% CI -39.70 to 21.45), albumin (mean=23.71 g/L, MD = -8.16, 95% CI -11.46 to -4.86). Lymphocyte, creatinine, urea, and alanine transaminase parameters were increased in some studies and decreased in others. CLINICAL SIGNIFICANCE: In canine pyometra, some blood parameters are consistently increased, some consistently decreased, and some increased or decreased depending on the study.

Complete mesocolic excision for right hemicolectomy: an updated systematic review and meta-analysis.

PURPOSE: Complete mesocolic excision improves lymphadenectomy for right hemicolectomy and respects the embryological planes. However, its effect on cancer-free and overall survival is questioned. Therefore, we aimed to determine the potential benefits of the technique by performing a systematic review of the literature and meta-analysis of the available evidence. METHODS: Web of Science, PubMed/Medline, and Embase were searched on February 22, 2023. Original studies on short- and long-term oncological outcomes of adult patients undergoing right hemicolectomy with complete mesocolic excision as a treatment for primary colon cancer were considered for inclusion. Outcomes were extracted and pooled using a model with random effects. RESULTS: A total of 586 publications were identified through database searching, and 18 from citation searching. Exclusion of 552 articles left 24 articles for inclusion. Meta-analysis showed that complete mesocolic excision increased the lymph node harvest (5 studies, 1479 patients, MD 9.62, 95% CI 5.83-13.41, p > 0.0001, I2 84%), 5-year overall survival (5 studies, 2381 patients, OR 1.88, 95% CI 1.14-3.09, p = 0.01, I2 66%), 5-year disease-free survival (4 studies, 1376 patients, OR 2.21, 95% CI 1.51-3.23, p < 0.0001, I2 0%) and decreased the incidence of local recurrence (4 studies, 818 patients, OR 0.27, 95% CI 0.09-0.79, p = 0.02, I2 0%) when compared to standard right hemicolectomy. Perioperative morbidity was similar between the techniques (8 studies, 3899 patients, OR 1.04, 95% CI 0.89-1.22, p = 0.97, I2 0%). CONCLUSION: Meta-analysis of observational and randomised studies showed that right hemicolectomy with complete mesocolic excision for primary right colon cancer improves oncologic results without increasing morbidity/mortality. These results need to be confirmed by high-quality evidence and randomised trials in selected patients to assess who may benefit from the procedure.

Stress indicators in minorities with multiple sclerosis.

Black Americans with multiple sclerosis (MS) experience higher levels of disease-related disability compared to White Americans (Marrie et al., 2006). Comorbidities such as depression and anxiety, which are underdiagnosed and undertreated in this population, negatively impact quality of life and treatment outcomes for people living with multiple sclerosis (plwMS) (D'Alisa et al., 2006; Marrie et al., 2009; Stepleman et al., 2014). Acts of discrimination toward Black Americans is associated with stress, which is a contributing factor for depression (Carter, 2017; Nadimpalli, 2015; Williams and Mohammed, 2009). This study compared the severity of multiple sclerosis symptoms amongst Black Americans and White Americans, and whether worsened MS symptoms in Black Americans are associated with increased experiences of discrimination. Data was analyzed from 143 plwMS in the Stress Indicators in Minorities with Multiple Sclerosis (SiMMS) study. Using the Mann-Whitney U test, significant differences were found on the NIH Emotional Distress - Anxiety measure (U = 1466.500, p = 0.045) and NIH Sleep Disturbance measure (U = 1467.000, p = 0.044) between the Black participant and the White participant groups. Discrimination was significantly correlated with both NIH Emotional Distress - Anxiety (r = 0.677, p < .001) and NIH Sleep Disturbance (r = 0.446, p = .007) in Black MS individuals. Additionally, several physiological condition and psychological outcome measures were correlated with the NIH Emotional Distress - Anxiety and NIH Sleep Disturbance measures. This study contributes to literature highlighting the negative impacts of discrimination and race related stress on the physical and mental health of Black Americans.

National Data and the Applicability to Understanding Rural and Remote Substance Use.

Responding to increases in overdose, addiction, and substance misuse, local public health experts need accurate data to plan and implement evidence-based prevention and treatment programs. In many countries, national data are the tool most readily available for these efforts. In the United States, the National Study on Drug Use and Health and the Treatment Episode Data Set are data sources used by states to determine the extent of addiction. This project sought to determine if these national data sources are applicable for local use in addiction prevention and program planning. NSDUH prevalence estimates from 2015 to 2019 were applied to the state population to determine the number of persons estimated to be substance users. The prevalence estimates were compared over time with the population data and substance use treatment admissions to assess the covariance and population change as an indicator of efficacy. The primary drivers of fatal overdose in Alaska are fentanyl, heroin, and methamphetamine. Fentanyl use was not assessed in either dataset. When applying the estimated use prevalence to the population, heroin users varied annually by 1777 persons and methamphetamine varied up to 2143 persons. These observed variances did not correspond with state population changes nor any trend in the persons seeking treatment for these substances. Our analyses do not support the use of NSDUH data for planning in rural and remote areas. The methods used in NSDUH data collection exclude ~ 20% of the state population, mostly Native persons, based on location and language. The annual prevalence estimates applied to the population did not correspond with changes in population nor changes in treatment. Fentanyl, which causes the most overdoses in Alaska and is of primary concern locally, was not assessed.

Transcriptional and Epigenetic Regulation of Context-Dependent Plasticity in T-Helper Lineages.

Th cell lineage determination and functional specialization are tightly linked to the activation of lineage-determining transcription factors (TFs) that bind cis-regulatory elements. These lineage-determining TFs act in concert with multiple layers of transcriptional regulators to alter the epigenetic landscape, including DNA methylation, histone modification and three-dimensional chromosome architecture, in order to facilitate the specific Th gene expression programs that allow for phenotypic diversification. Accumulating evidence indicates that Th cell differentiation is not as rigid as classically held; rather, extensive phenotypic plasticity is an inherent feature of T cell lineages. Recent studies have begun to uncover the epigenetic programs that mechanistically govern T cell subset specification and immunological memory. Advances in next generation sequencing technologies have allowed global transcriptomic and epigenomic interrogation of CD4+ Th cells that extends previous findings focusing on individual loci. In this review, we provide an overview of recent genome-wide insights into the transcriptional and epigenetic regulation of CD4+ T cell-mediated adaptive immunity and discuss the implications for disease as well as immunotherapies.

Erratum: Publisher Correction: Relevant mathematical modelling efforts for understanding COVID-19 dynamics: an educational challenge.

[This corrects the article DOI: 10.1007/s11858-022-01447-2.].

Relevant mathematical modelling efforts for understanding COVID-19 dynamics: an educational challenge.

The purpose of the work described in this paper is to emphasize the importance of using mathematical models and mathematical modelling in order to be able to understand and to learn possible behaviours in epidemic situations such as that of the COVID-19 pandemic, besides suggesting modelling techniques with which to evaluate certain sanitary decisions and policies which do, in fact, affect society as a whole. The mathematical tools that are used derive from nonlinear systems of difference equations (possibly viable at a high school level, using spreadsheets or adequate software) as well as nonlinear systems of ordinary differential equations (therefore using mathematical tools and software well within the reach of undergraduate students of many courses). This purpose is accomplished by motivating students and learners to study existing SIR-type models and modifying them in order to have a fully understandable translation of dynamics for infectious diseases such as COVID-19 in several different realistic scenarios, that is to say, situations that consider social distancing policies, widespread vaccination programmes, as well as possible and even probable results when in the presence of negationist postures and attitudes. Several modelling choices referring to real-life situations are shown and explored. These models are analysed and discussed, implicitly proposing similar attitudes and evaluations in learning environments. Conclusions are drawn, stimulating further work using the described mathematical tools and resources. Supplementary Information: The online version contains supplementary material available at 10.1007/s11858-022-01447-2.

Dynamics of Viral and Host 3D Genome Structure upon Infection.

Eukaryotic chromatin is highly organized in the 3D nuclear space and dynamically regulated in response to environmental stimuli. This genomic organization is arranged in a hierarchical fashion to support various cellular functions, including transcriptional regulation of gene expression. Like other host cellular mechanisms, viral pathogens utilize and modulate host chromatin architecture and its regulatory machinery to control features of their life cycle, such as lytic versus latent status. Combined with previous research focusing on individual loci, recent global genomic studies employing conformational assays coupled with high-throughput sequencing technology have informed models for host and, in some cases, viral 3D chromosomal structure re-organization during infection and the contribution of these alterations to virus-mediated diseases. Here, we review recent discoveries and progress in host and viral chromatin structural dynamics during infection, focusing on a subset of DNA (human herpesviruses and HPV) as well as RNA (HIV, influenza virus and SARS-CoV-2) viruses. An understanding of how host and viral genomic structure affect gene expression in both contexts and ultimately viral pathogenesis can facilitate the development of novel therapeutic strategies.

The developmental consequences of early adverse care on infant macaques: A cross-fostering study.

Early life adversity/stress (ELA/ELS), particularly adverse caregiving experiences such as child maltreatment (MALT), is a main risk factor for psychopathology, including psychiatric disorders such as anxiety, depression, ADHD, and substance abuse. Yet how these alterations unfold during development and the underlying mechanisms remain poorly understood, as it is difficult to prospectively and longitudinally study early developmental phases in humans, and nearly impossible to disentangle postnatal caregiving effects from heritable traits. This study examined the specific effects of "nurture" (maternal care) versus "nature" (heritable, biological maternal factors) on nonhuman primate infant socioemotional, stress neuroendocrine, and physical development. For this we used a translational and naturalistic macaque model of infant maltreatment by the mother with randomized assignment at birth to either mothers with a history of maltreating their infants (MALT group, n = 22) or to competent mothers (Control group, n = 20). Over the first 6 months of life (roughly equivalent to 2 years in humans), we examined the development of the mother-infant relationship, as well as infants' social behavior and emotional reactivity. In parallel, we assessed hypothalamic-pituitary-adrenal (HPA) axis function longitudinally, using measures of hair cortisol accumulation, and basal morning plasma cortisol. We identified broad impairments in maternal care exhibited by MALT foster mothers, beyond maltreatment (physical abuse, rejection) events, suggesting that MALT foster mothers provide an overall lower quality of care to their infants compared to Controls. MALT infants exhibited alterations in their initiations and breaks of proximity towards their mothers, as well as heightened emotional reactivity in comparison to Controls. Most striking are the HPA axis findings, with MALT infants showing higher levels of plasma cortisol across the first 6 postnatal months as well as higher hair cortisol accumulation from birth through month 6 (a signature of chronic stress) than Controls. No caregiving effects were detected on physical growth, which ruled out confounding effects of maternal nutrition, metabolism, etc. Taken together, these results suggest that the developmental trajectory of MALT and Control infants is different, marked by heightened levels of emotional reactivity, increased HPA activity and alterations in mother-infant interactions in MALT animals. These findings appear to be due to specific effects of postnatal maternal care, and not to biological/ behavioral traits inherited from the mother, or due to prenatal programming caused by prenatal stress, as the cross-fostering design controlled for these potential factors. However, we also detected a couple of interesting biological effects suggesting heritable transmission of some phenotypes. The prolonged HPA axis activation during the first 6 postnatal months of life is expected to have long-term consequences for brain, physiological, and behavioral development in MALT offspring.

[Teaching otorhinolaryngology in times of COVID-19: to what extent can digital formats replace face-to-face teaching?] / Unterricht in der Hals-Nasen-Ohren-Heilkunde in Zeiten der COVID-19-Pandemie. Wie gut können digitale Formate die Präsenzlehre ersetzen?

OBJECTIVE: Due to the coronavirus disease 19 (COVID-19) pandemic, postgraduate training in otorhinolaryngology in 2020 was transferred completely from face-to-face to digital teaching. This paper assesses whether this change was possible without a reduction in the quality of teaching and learning. METHODS: Results of final written examinations were compared for the years 2016-2020, and the results of the teaching evaluation by the students for 2017-2020. The evaluation by students in 2020 included additional questions related to the switch from face-to-face to digital teaching. Additionally, the lecturers and teachers were asked for their assessments. RESULTS: Results of the final written examination did not show any significant differences between 2016-2019 and 2020. Students were highly satisfied with the digital format, but values did not reach the level of former years with face-to-face-teaching. Especially the interaction with patients and the teaching of manual skills were rated lower in the digital format. Lecturers emphasized the additional workload for preparation of digital teaching. CONCLUSION: The results of written examinations showed no difference between digital and face-to-face teaching. Online communication and interaction were reduced and regarded as cumbersome by students and faculty. Digital solutions providing more interaction and active participation are required. The digital format is more appropriate for teaching basic knowledge than for teaching practical skills.

Intercalary and geographic lower limb tumor resections with the use of 3D printed Patient Specific Instruments- when less is more.

Background: Primary bone sarcomas are associated with critically sized bone defects and require complete resection with negative margins. Recent advancements in health care have pioneered novel approaches such as the implementation of 3D surgical technologies. This study presents oncological and functional outcomes following tumor resections of long bones with the use of customized 3D-printed Patient Specific Instruments (PSIs). Methods: This single-center retrospective study is comprised of seventeen patients who underwent either intercalary (N = 12) or geographic (N = 5) resections with various reconstruction methods including allograft (N = 8), vascularized fibula (Capanna) (N = 7), and 3D printed customized titanium implants (N = 2), between the years 2016-2020. All patients were operated on with a 3D surgical workflow, including intraoperative PSIs, and were followed up postoperatively for at least 12 months (average 31.40 ± 12.13 months) to assess oncological and functional outcomes. Results: All patients demonstrated negative surgical margins, apart from one patient who had planned positive margins. Three patients suffered from short-term complications, and three patients underwent revision surgery due to graft non-union or pathological fracture. One patient suffered from local recurrence and underwent above-knee amputation. Three patients suffered from lung metastasis. MSTS at 12-month follow-up was 26.9.±5.87. Conclusion: Customized 3D-printed osteotomy PSIs provide surgeons with a novel tool for optimizing bone resection and reconstruction in long bones surgeries, thus minimizing overall tissue trauma and reducing the risk of damage to nervous and vascular structures. This study demonstrates that the use of PSIs has the potential to improve functional and oncological outcomes. We believe that this technique will become increasingly popular in the future as a widely applicable, highly accurate, cost-effective optimization tool.

MRI Findings after Recent Image-Guided Lumbar Puncture: The Rate of Dural Enhancement and Subdural Collections.

BACKGROUND AND PURPOSE: The rate of abnormal intracranial MR imaging findings including subdural collections and dural enhancement after recent lumbar puncture is not known. The purpose of our study was to examine the intracranial MR imaging findings after recent image-guided lumbar puncture. MATERIALS AND METHODS: Patients who underwent contrast-enhanced MR imaging of the brain within 7 days of a CT-guided lumbar puncture between January 2014 and April 2021 were included. Contrast-enhanced MR images were reviewed for diffuse dural enhancement, morphologic findings of brain sag, dural venous sinus distension, and subdural collections. RESULTS: Of the 160 patients who met the inclusion criteria, only 6 patients (3.9%) had new diffuse dural enhancement, though none had dural enhancement when the MR imaging was within 2 days of lumbar puncture. All 6 patients with dural enhancement had small, concurrent subdural collections. Two additional patients had subdural collections, for a total of 5.2% of our population. CONCLUSIONS: Our study is the first to examine intracranial MR imaging after recent lumbar puncture and has 2 key findings: First, 5.2% of patients had small, bilateral subdural collections after recent lumbar puncture, suggesting that asymptomatic subdural collections after recent lumbar puncture are not atypical and do not require further work-up. Additionally, when MR imaging was performed within 2 days of lumbar puncture, none of our patients had diffuse dural enhancement. This argues against the commonly held practice of performing MR imaging before lumbar puncture to avoid findings of dural enhancement, and should not delay diagnostic work-up.

Efficacy and Safety of Reirradiation with Stereotactic Body Radiation Therapy for Locally Recurrent Pancreatic Adenocarcinoma.

AIMS: The purpose of this study was to report on outcomes of a cohort of patients who were treated with reirradiation with stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients treated with SBRT reirradiation for locally recurrent pancreatic adenocarcinoma from December 2009 to April 2020 were included in the study. Descriptive statistics were used to record patient demographics, tumour and treatment characteristics. Kaplan-Meier analysis was used to evaluate overall survival, local progression-free survival (LPFS), distant metastasis-free survival and progression-free survival (PFS). RESULTS: In total, 27 patients were included in the study. The median follow-up time from local recurrence was 19.7 months (range 4.2-43.1 months). Most patients received five-fraction SBRT (26/27, 96%). The median overall survival after local recurrence treatment was 18.3 months (range 3.0-42.6 months), with 6-month, 1-year and 2-year overall survival rates of 88.5%, 73.1% and 33.6%. The median LPFS after local recurrence treatment was 16.2 months (range 2.3-33.6 months), with 6-month, 1-year and 2-year LPFS rates of 95.8%, 62.9% and 27.2%. Peri-SBRT chemotherapy improved LPFS (median 17.5 versus 8.5 months; P = 0.010) and overall survival (median 19.3 versus 5.5 months; P = 0.049). Tumours ≤ 3 cm in the greatest dimension showed better local control (median LPFS 19.2 versus 10.2 months; P = 0.130). There was one case (4%) of acute grade 3 pain and one case (4%) of late grade 3 gastrointestinal toxicity. CONCLUSIONS: Reirradiation with five-fraction SBRT is safe, but local control remains suboptimal. Patients with smaller tumours experienced improved outcomes, as did patients whose treatment plan included the administration of peri-SBRT chemotherapy.

A national, multicentre, web-based point prevalence survey of antimicrobial use and quality indices among hospitalised paediatric patients across South Africa.

OBJECTIVES: Data on antimicrobial consumption among the paediatric population in public hospitals in South Africa are limited. This needs to be addressed to improve future antimicrobial use and reduce antimicrobial resistance rates. This study aimed to quantify antimicrobial usage and to identify and classify which antimicrobials are used in the paediatric population in public sector hospitals in South Africa according to the World Health Organization (WHO) AWaRe list of antimicrobials. METHODS: A point prevalence survey was conducted among 18 public sector hospitals from nine provinces using a newly developed web-based application. Data were analysed according to the WHO AWaRe list to guide future quality improvement programmes. RESULTS: A total of 1261 paediatric patient files were reviewed, with 49.7% (627/1261) receiving at least one antimicrobial and with 1013 antimicrobial prescriptions overall. The top five antimicrobials included ampicillin (16.4%), gentamicin (10.0%), amoxicillin/enzyme inhibitor (9.6%), ceftriaxone (7.4%) and amikacin (6.3%). Antimicrobials from the 'Access' classification were the most used (55.9%), with only 3.1% being from the 'Reserve' classification. The most common infectious conditions for which an antimicrobial was prescribed were pneumonia (14.6%; 148/1013) and clinical sepsis (11.0%; 111/1013). Parenteral administration (75.6%; 766/1013) and prolonged surgical prophylaxis (66.7%; 10/15) were common concerns. Only 28.0% (284/1013) of prescribed antimicrobials had cultures requested; of which only 38.7% (110/284) of culture results were available in the files. CONCLUSION: Overall, antimicrobial prescribing is common among paediatric patients in South Africa. Interventions should be targeted at improving antimicrobial prescribing, including surgical prophylaxis, and encouraging greater use of oral antibiotics.

A systematic review and meta-analysis of robotic-assisted transabdominal total mesorectal excision and transanal total mesorectal excision: which approach offers optimal short-term outcomes for mid-to-low rectal adenocarcinoma?

BACKGROUND: Resection of low rectal adenocarcinoma can be challenging in the narrow pelvis of male patients. Transanal total mesorectal excision (TaTME) appears to offer technical advantages for distal rectal tumours, and robotic-assisted transabdominal TME (rTME) was introduced in effort to improve operative precision and ergonomics. However, no study has comprehensively compared these approaches. The aim of the present study was to perform a systematic review of the literature to compare postoperative short-term outcomes in rTME and TaTME. METHODS: A systematic online search (1974-July 2020) of MEDLINE, Embase, web of science and google scholar was conducted for trials, prospective or retrospective studies involving rTME, or TaTME for rectal cancer. Outcome variables included: hospital stay; operation duration, blood loss; resection margins; proportion of histologically complete resected specimens; lymph nodes; overall complications; anastomotic leak, and 30-day mortality. RESULTS: Sixty-two articles met the inclusion criteria, including 37 studies (3835 patients) assessing rTME resection, 23 studies (1326 patients) involving TaTME and 2 comparing both (165 patients). Operating time was longer in rTME (309.2 min, 95% CI 285.5-332.8) than in TaTME studies (256.2 min, 95% CI 231.5-280.9) (p = 0.002). rTME resected specimens had a larger distal resection margin (2.62 cm, 95% CI 2.35-2.88) than in TaTME studies (2.10 cm, 95% CI 1.83-2.36) (p = 0.007). Other outcome variables did not significantly differ between the two techniques. CONCLUSIONS: rTME provides similar pathological and short-term outcomes to TaTME and both are reasonable surgical approaches for patients with mid-to-low rectal cancer. To definitively answer the question of the optimal TME technique, we suggest a prospective trial comparing both techniques assessing long-term survival as a primary outcome.