Society of Surgical Oncology Breast Disease Site Working Group Statement on Contralateral Mastectomy: Indications, Outcomes, and Risks.

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.

Unexpected Single-Ligand Occupancy and Negative Cooperativity in the SARS-CoV-2 Main Protease.

Many homodimeric enzymes tune their functions by exploiting either negative or positive cooperativity between subunits. In the SARS-CoV-2 Main protease (Mpro) homodimer, the latter has been suggested by symmetry in most of the 500 reported protease/ligand complex structures solved by macromolecular crystallography (MX). Here we apply the latter to both covalent and noncovalent ligands in complex with Mpro. Strikingly, our experiments show that the occupation of both active sites of the dimer originates from an excess of ligands. Indeed, cocrystals obtained using a 1:1 ligand/protomer stoichiometry lead to single occupation only. The empty binding site exhibits a catalytically inactive geometry in solution, as suggested by molecular dynamics simulations. Thus, Mpro operates through negative cooperativity with the asymmetric activity of the catalytic sites. This allows it to function with a wide range of substrate concentrations, making it resistant to saturation and potentially difficult to shut down, all properties advantageous for the virus' adaptability and resistance.

Erratum: Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours.

This corrects the article DOI: 10.1038/nature24993.

Juvenile Xanthogranuloma of the Head and Neck: Imaging Findings in 11 Cases.

BACKGROUND: Juvenile Xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis, occurring mainly in infancy. With an extracutaneous lesion, its diagnosis is difficult, because of a wide clinical spectrum. Here we demonstrate and characterize imaging features of 11 patients with JXG of the head and neck in various locations. MATERIAL AND METHODS: We recorded clinical data and reviewed all imaging studies of 11 patients with JXG of the head and neck. Ultrasonography (US) alone was performed in 1 patient; MRI alone in 6 patients; US and MRI in 1 patient; and US, CT, and MRI in 3 patients. We evaluated the following characteristics in all studies: location and number of lesions, echogenicity and vascularization on US, density on CT, signal intensity on T1- and T2-weighted images, ADC and enhancement on MRI, and tumor boundaries and bone involvement. RESULTS: Lesions were well-defined in 9 cases, and bone erosion was present in 2. On US, lesions were hypoechoic or hyperechoic and with or without vascularization. On CT, lesions were hyper-dense, with no calcification. On MRI, lesions were mildly hyper-intense or iso-intense on T1-weighted images in 8 of 9 patients, hypo-intense on T2-weighted images in 7 of 10, low ADC in 7 of 9, and enhancement in 7 of 7. CONCLUSIONS: The diagnosis of extra cutaneous JXG may be proposed, with the following suggestive criteria: age < 1 year, well-defined lesion, mild hyper-intensity on T1-weighted images, hypo-intensity on T2-weighted images, low ADC, enhancement, and possible adjacent bone involvement.

Deciphering the free energy landscapes of SARS-CoV-2 wild type and Omicron variant interacting with human ACE2.

The binding of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein to the host cell receptor angiotensin-converting enzyme 2 (ACE2) is the first step in human viral infection. Therefore, understanding the mechanism of interaction between RBD and ACE2 at the molecular level is critical for the prevention of COVID-19, as more variants of concern, such as Omicron, appear. Recently, atomic force microscopy has been applied to characterize the free energy landscape of the RBD-ACE2 complex, including estimation of the distance between the transition state and the bound state, xu. Here, using a coarse-grained model and replica-exchange umbrella sampling, we studied the free energy landscape of both the wild type and Omicron subvariants BA.1 and XBB.1.5 interacting with ACE2. In agreement with experiment, we find that the wild type and Omicron subvariants have similar xu values, but Omicron binds ACE2 more strongly than the wild type, having a lower dissociation constant KD.

Mfsd7b facilitates choline transport and missense mutations affect choline transport function.

MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA) and intracellular choline levels, but it is independent of gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.

Using AI to Improve Radiologist Performance in Detection of Abnormalities on Chest Radiographs.

Background Chest radiography remains the most common radiologic examination, and interpretation of its results can be difficult. Purpose To explore the potential benefit of artificial intelligence (AI) assistance in the detection of thoracic abnormalities on chest radiographs by evaluating the performance of radiologists with different levels of expertise, with and without AI assistance. Materials and Methods Patients who underwent both chest radiography and thoracic CT within 72 hours between January 2010 and December 2020 in a French public hospital were screened retrospectively. Radiographs were randomly included until reaching 500 radiographs, with about 50% of radiographs having abnormal findings. A senior thoracic radiologist annotated the radiographs for five abnormalities (pneumothorax, pleural effusion, consolidation, mediastinal and hilar mass, lung nodule) based on the corresponding CT results (ground truth). A total of 12 readers (four thoracic radiologists, four general radiologists, four radiology residents) read half the radiographs without AI and half the radiographs with AI (ChestView; Gleamer). Changes in sensitivity and specificity were measured using paired t tests. Results The study included 500 patients (mean age, 54 years ± 19 [SD]; 261 female, 239 male), with 522 abnormalities visible on 241 radiographs. On average, for all readers, AI use resulted in an absolute increase in sensitivity of 26% (95% CI: 20, 32), 14% (95% CI: 11, 17), 12% (95% CI: 10, 14), 8.5% (95% CI: 6, 11), and 5.9% (95% CI: 4, 8) for pneumothorax, consolidation, nodule, pleural effusion, and mediastinal and hilar mass, respectively (P < .001). Specificity increased with AI assistance (3.9% [95% CI: 3.2, 4.6], 3.7% [95% CI: 3, 4.4], 2.9% [95% CI: 2.3, 3.5], and 2.1% [95% CI: 1.6, 2.6] for pleural effusion, mediastinal and hilar mass, consolidation, and nodule, respectively), except in the diagnosis of pneumothorax (-0.2%; 95% CI: -0.36, -0.04; P = .01). The mean reading time was 81 seconds without AI versus 56 seconds with AI (31% decrease, P < .001). Conclusion AI-assisted chest radiography interpretation resulted in absolute increases in sensitivity for all radiologists of various levels of expertise and reduced the reading times; specificity increased with AI, except in the diagnosis of pneumothorax. © RSNA, 2023 Supplemental material is available for this article.

Genetic diversity in the capsid protein gene of porcine circovirus type 3 in Vietnam from 2018 to 2019.

Porcine circovirus type 3 (PCV3) was first detected in 2016 and has been reported in many pig-producing countries around the world, including Vietnam. PCV3 has been found in complex cases with multiple clinical syndromes in swine. In this study, we investigated the genetic diversity of PCV3 strains circulating in Vietnam. A total of 249 samples were collected from swine farms located in eight provinces of Vietnam, and 11.65% (29/249) of these samples were found to contain PCV3. The ORF2 genes from the 29 PCV3-positive samples were amplified, purified, and sequenced. Phylogenetic analysis showed that 23 of these strains belonged to the PCV3b subtype, while the remaining six strains belonged to subtype c and subtype a (a-1 and a-2). Analysis of the ORF2 genes indicated that the 29 PCV3 strains had high sequence identity (96.90-100% at the genomic level and 96.19-100% at the amino acid level). Fifteen amino acid substitutions were found in predicted B-cell epitopes in the capsid proteins of the Vietnamese PCV3 strains.

The impact of cold waves and heat waves on mortality: Evidence from a lower middle-income country.

We estimate the impact of temperature extremes on mortality in Vietnam, using daily data on temperatures and monthly data on mortality during the 2000-2018 period. We find that both cold and heat waves cause higher mortality, particularly among older people and those living in the hot regions in Southern Vietnam. This effect on mortality tends to be smaller in provinces with higher rates of air-conditioning and emigration, and provinces with higher public spending on health. Finally, we estimate economic cost of cold and heat waves using a framework of willingness to pay to avoid deaths, then project the cost to the year 2100 under different Representative Concentration Pathway scenarios.

Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours.

Tissue-resident memory CD8+ T (TRM) cells are found at common sites of pathogen exposure, where they elicit rapid and robust protective immune responses. However, the molecular signals that control TRM cell differentiation and homeostasis are not fully understood. Here we show that mouse TRM precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory cell populations at the levels of gene expression and chromatin accessibility. Using computational and pooled in vivo RNA interference screens, we identify the transcription factor Runx3 as a key regulator of TRM cell differentiation and homeostasis. Runx3 was required to establish TRM cell populations in diverse tissue environments, and supported the expression of crucial tissue-residency genes while suppressing genes associated with tissue egress and recirculation. Furthermore, we show that human and mouse tumour-infiltrating lymphocytes share a core tissue-residency gene-expression signature with TRM cells that is associated with Runx3 activity. In a mouse model of adoptive T cell therapy for melanoma, Runx3-deficient CD8+ tumour-infiltrating lymphocytes failed to accumulate in tumours, resulting in greater rates of tumour growth and mortality. Conversely, overexpression of Runx3 enhanced tumour-specific CD8+ T cell abundance, delayed tumour growth, and prolonged survival. In addition to establishing Runx3 as a central regulator of TRM cell differentiation, these results provide insight into the signals that promote T cell residency in non-lymphoid sites, which could be used to enhance vaccine efficacy or adoptive cell therapy treatments that target cancer.

Abnormalities of the corpus callosum. Can prenatal imaging predict the genetic status? Correlations between imaging phenotype and genotype.

OBJECTIVE: Recent studies have evaluated prenatal exome sequencing (pES) for abnormalities of the corpus callosum (CC). The objective of this study was to compare imaging phenotype and genotype findings. METHOD: This multicenter retrospective study included fetuses with abnormalities of the CC between 2018 and 2020 by ultrasound and/or MRI and for which pES was performed. Abnormalities of the CC were classified as complete (cACC) or partial (pACC) agenesis of the CC, short CC (sCC), callosal dysgenesis (CD), interhemispheric cyst (IHC), or pericallosal lipoma (PL), isolated or not. Only pathogenic (class 5) or likely pathogenic (class 4) (P/LP) variants were considered. RESULTS: 113 fetuses were included. pES identified P/LP variants for 3/29 isolated cACC, 3/19 isolated pACC, 0/10 isolated sCC, 5/10 isolated CD, 5/13 non-isolated cACC, 3/6 non-isolated pACC, 8/11 non-isolated CD and 0/12 isolated IHC and PL. Associated cerebellar abnormalities were significantly associated with P/LP variants (OR = 7.312, p = 0.027). No correlation was found between phenotype and genotype, except for fetuses with a tubulinopathy and an MTOR pathogenic variant. CONCLUSIONS: P/LP variants were more frequent in CD and in non-isolated abnormalities of the CC. No such variants were detected for fetuses with isolated sCC, IHC and PL.

Postnatal deletion of Spns2 prevents neuroinflammation without compromising blood vascular functions.

Protein Spinster homolog 2 (Spns2) is a sphingosine-1-phosphate (S1P) transporter that releases S1P to regulate lymphocyte egress and trafficking. Global deletion of Spns2 (Spns2-/-) has been shown to reduce disease severity in several autoimmune disease models. To examine whether Spns2 could be exploited as a drug target, we generated and characterized the mice with postnatal knockout of Spns2 (Spns2-Mx1Cre). Our results showed that Spns2-Mx1Cre mice had significantly low number of lymphocytes in blood and lymphoid organs similar to Spns2-/- mice. Lymph but not plasma S1P levels were significantly reduced in both groups of knockout mice. Our lipidomic results also showed that Spns2 releases different S1P species into lymph. Interestingly, lymphatic vessels in the lymph nodes (LNs) of Spns2-/- and Spns2-Mx1Cre mice exhibited morphological defects. The structures of high endothelial venules (HEV) in the LNs of Spns2-Mx1Cre mice were disorganized. These results indicate that lack of Spns2 affects both S1P secretion and LN vasculatures. Nevertheless, blood vasculature of these Spns2 deficient mice was not different to controls under homeostasis and vascular insults. Importantly, Spns2-Mx1Cre mice were resistant to multiple sclerosis in experimental autoimmune encephalomyelitis (EAE) models with significant reduction of pathogenic Th17 cells in the central nervous system (CNS). This study suggests that pharmacological inhibition of Spns2 may be exploited for therapeutic applications in treatment of neuroinflammation.

Equivalence of care, confidentiality, and professional independence must underpin the hospital care of individuals experiencing incarceration.

We present the reflections of three clinical practitioners on ethical considerations when caring for individuals experiencing incarceration needing in-patient hospital services. We examine the challenges and critical importance of adhering to core principles of medical ethics in such settings. These principles encompass access to a physician, equivalence of care, patient's consent and confidentiality, preventive healthcare, humanitarian assistance, professional independence, and professional competence. We strongly believe that detained persons have a right to access healthcare services that are equivalent to those available in the general population, including in-patient services. All the other established standards to uphold the health and dignity of people experiencing incarceration should also apply to in-patient care, whether this takes place outside or inside the prison boundaries. Our reflection focuses on the principles of confidentiality, professional independence, and equivalence of care. We argue that the respect for these three principles, although they present specific implementation challenges, is foundational for implementing the other principles. Critically important are respect for the distinct roles and responsibilities of healthcare and security staff as well as transparent and non-hierarchical dialogue between them to ensure optimal health outcomes and functioning of hospital wards while balancing the ongoing tensions between care and control.

Erythrocytes efficiently utilize exogenous sphingosines for S1P synthesis and export via Mfsd2b.

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that exerts its activity via activation of five different G protein-coupled receptors, designated as S1P1-5. This potent lipid mediator is synthesized from the sphingosine precursor by two sphingosine kinases (SphK1 and 2) and must be exported to exert extracellular signaling functions. We recently identified Mfsd2b as the S1P transporter in the hematopoietic system. However, the sources of sphingosine for S1P synthesis and the transport mechanism of Mfsd2b in erythrocytes remain to be determined. Here, we show that erythrocytes efficiently take up exogenous sphingosine and that a de novo synthesis pathway in part provides sphingosines to erythrocytes. The uptake of sphingosine in erythrocytes is facilitated by the activity of SphK1. By converting sphingosine into S1P, SphK1 indirectly increases the influx of sphingosine, a process that is irreversible in erythrocytes. Our results explain for the abnormally high amount of sphingosine accumulation in Mfsd2b knockout erythrocytes. Furthermore, we show that Mfsd2b utilizes a proton gradient to facilitate the release of S1P. The negatively charged residues D95 and T157 are essential for Mfsd2b transport activity. Of interest, we also discovered an S1P analog that inhibits S1P export from erythrocytes, providing evidence that sphingosine analogs can be used to inhibit S1P export by Mfsd2b. Collectively, our results highlight that erythrocytes are efficient in sphingosine uptake for S1P production and the release of S1P is dependent on Mfsd2b functions.

Innovation in Breast Surgery: Practical and Ethical Considerations.

The adoption of innovation is essential to the evolution of patient care. Breast surgical oncology advances through incorporating new techniques, devices, and procedures. Historical changes in practice standards from radical to modified radical mastectomy or axillary node dissection to sentinel node biopsy reduced morbidity without sacrifice in oncologic outcome. Contemporary oncoplastic techniques afford broader consideration for breast conservation and the potential for improved cosmetic outcomes. At present, many breast surgeons face the decision of which wireless device to use for localization of nonpalpable lesions. Consideration for future changes, such as robotic mastectomy, are on the horizon. No guideline exists to assist breast surgeons in the adoption of innovation into practice. The Ethics Committee of the American Society of Breast Surgeons acknowledges that breast surgeons confront many questions associated with onboarding innovation. This paper aims to provide a framework for asking relevant questions along with the ethical principles to consider when integrating an innovation into practice.

Anterior cruciate ligament foot plate anatomy: 3-dimensional and 2-dimensional MRI evaluation with arthroscopy assessment in a subset of patients.

OBJECTIVES: ACL reconstruction tunnel location is an important predictor for outcomes after surgery. The aim was to establish 3D and 2D MRI radiological measurements for native ACL tibial footprint that can provide information to facilitate pre-operative planning for anatomical graft placement. The measurements were also correlated in a subset of patients on arthroscopy. METHODS: Retrospective evaluation of a consecutive series of knee MRIs with both 2D and 3D MR imaging was performed in 101 patients with 43 men and 66 women and ages 39.5 ± 11.9 years. Two measurements were obtained, tibial to ACL and intermeniscal ligament to ACL (T-ACL) and (IM-ACL), respectively. In a cohort of 18 patients who underwent knee arthroscopy, the T-ACL and IML-ACL distances were also determined by an orthopedic surgeon using a standard scale. ICC, Pearson correlation, and Bland-Altman plot were generated. RESULTS: For readers 1 and 2, the mean differences between 2D and 3D measurements of T-ACL and IM-ACL were 1.17 and 1.03 mm and 0.65 and 0.65 mm, respectively. The 2D measurements of T-ACL and IM-ACL were larger than the 3D measurements for both readers. The inter-reader reliability was excellent on 2D (0.81-0.96) and fair to excellent on 3D MRI (0.59-0.90). The mean arthroscopic IML-ACL was closer to that of 3D MRI compared to 2D MRI. The mean arthroscopic T-ACL was closer to 2D MRI than 3D MRI. CONCLUSIONS: Both 2D and 3D MRI show inter-reader reliability with small inter-modality mean differences in the measurements from the tibial or inter-meniscal ligament margins. KEY POINTS: • The mean differences between 2D and 3D measurements of tibia-ACL and intermeniscal ligament-ACL are small (< 1.2 mm). • As compared to arthroscopy, the mean T-ACL and IML-ACL were closer to measurements from 2D and 3D MRI, respectively. • Both 2D and 3D MRI can be reliably used to delineate ACL foot plate anatomy.

Do Internal Migration Experiences Facilitate Migration Intentions and Behavior?

Growing evidence suggests that internal migration experience shapes future internal migration behavior. However, it remains unclear what stage of the decision-making process past internal migration facilitates and whether the impact depends on the distance moved. To advance understanding of the role of past migration, we explicitly and dynamically link migration experiences to the formation and realization of future internal migration intentions by blending the aspiration-ability framework with the learned behavior hypothesis. We empirically test our proposition by fitting a series of logistic regression models to longitudinal microdata from the Household, Income and Labour Dynamics in Australia (HILDA) Survey, which has been conducted annually since 2001. We use a two-step approach by first modeling internal migration intentions and then modeling the realization of these intentions, distinguishing between residential moves, onward interregional migration, and return interregional migration. We find that migration experience is positively associated with both the formation and realization of migration intentions and that the effect of past migration increases with the distance moved and the number of past migrations. These findings suggest that migration experiences accumulate over the life course to predispose individuals toward subsequent migration. Finally, we show that the effect of past migration is not the result of a lack of social capital among repeat migrants-a finding that reinforces the importance of conceptualizing internal migration as a life course trajectory rather than a series of discrete events.

Genetic Characterization of African Swine Fever Virus in Various Outbreaks in Central and Southern Vietnam During 2019-2021.

This study aimed to identify potential genetic diversity among African swine fever virus (ASFV) strains circulating in central and southern Vietnam. Thirty ASFV strains were collected from domestic pigs and convalescent pigs with ASFV-infected clinical signs from 19 different provinces of central and southern Vietnam during 2019-2021. A portion of the B646L (p72) gene and the entire E183L (p54), CP204L (p30), and B602L (CVR) genes were amplified, purified, and sequenced. Web-based BLAST and MEGA X software were used for sequence analysis. Analysis of the partial B646L (p72) gene, the full-length E183L (p54) and CP204L (p30) genes, and the central hypervariable region (CVR) of the B602L gene sequence showed that all 30 ASFV isolates belonged to genotype II and were 100% identical to the previously identified strains in Vietnam and China. Analysis of the p72, p54, and p30 regions did not indicate any change in the nucleotide and amino acid sequences among these strains in 3 years of research. No novel variant was found in the CVR within the B602L gene. Analysis of the CVR showed that these ASFV strains belong to subgroup XXXII. The results of this study revealed that these ASFVs shared high similarity with ASFV isolates detected previously in northern Vietnam and China. Taken together, the results of this study and a previous study in Vietnam showed high stability and no genetic diversity in the ASFV genome.

Self-care interventions for sexual and reproductive health in humanitarian and fragile settings: a scoping review.

BACKGROUND: Self-care is the ability of individuals, families, and communities to promote health, prevent disease, maintain health, and manage illness and disability with or without a health care provider. In resource-constrained settings with disrupted sexual and reproductive health (SRH) service coverage and access, SRH self-care could play a critical role. Despite SRH conditions being among the leading causes of mortality and morbidity among women of reproductive age in humanitarian and fragile settings, there are currently no reviews of self-care interventions in these contexts to guide policy and practice. METHODS: We undertook a scoping review to identify the design, implementation, and outcomes of self-care interventions for SRH in humanitarian and fragile settings. We defined settings of interest as locations with appeals for international humanitarian assistance or identified as fragile and conflict-affected situations by the World Bank. SRH self-care interventions were described according to those aligned with the Minimum Initial Services Package for Reproductive Health in Crises. We searched six databases for records using keywords guided by the PRISMA statement. The findings of each included paper were analysed using an a priori framework to identify information concerning effectiveness, acceptability and feasibility of the self-care intervention, places where self-care interventions were accessed and factors relating to the environment that enabled the delivery and uptake of the interventions. RESULTS: We identified 25 publications on SRH self-care implemented in humanitarian and fragile settings including ten publications on maternal and newborn health, nine on HIV/STI interventions, two on contraception, two on safe abortion care, one on gender-based violence, and one on health service provider perspectives on multiple interventions. Overall, the findings show that well-supported self-care interventions have the potential to increase access to quality SRH for crisis-affected communities. However, descriptions of interventions, study settings, and factors impacting implementation offer limited insight into how practical considerations for SRH self-care interventions differ in stable, fragile, and crisis-affected settings. CONCLUSION: It is time to invest in self-care implementation research in humanitarian settings to inform policies and practices that are adapted to the needs of crisis-affected communities and tailored to the specific health system challenges encountered in such contexts.

Audit of documentation accompanying referred maternity cases to a referral hospital in northern Ghana: a mixed-methods study.

BACKGROUND: Effective referral of maternity cases, which cannot be managed at the primary healthcare level, with detailed referral forms is important for reducing possible delays in the provision of higher-level healthcare. This is the first study to audit documentation or referral forms that accompany referred maternity cases to a referral hospital in the northern region of Ghana. MATERIALS AND METHODS: This study employed an explanatory sequential mixed-method design, starting with a quantitative review of referral forms that accompanied all patients referred to four units (antenatal, antenatal emergency, labour and neonatal intensive care) of a referral hospital in northern Ghana. In-depth interviews were held with the heads of the four units afterwards. Descriptive statistics were computed for the quantitative data. The qualitative data was subjected to content analysis. Integration of the data occurred at the data interpretation/discussion level. RESULTS: A total of 217 referral forms were analysed. Nearly half of the cases were referred from the Tamale Metropolis (46.5%) and 83.9% were referred for advanced care, whilst 8.3% were referred due to a lack of medical logistics and equipment such as oxygen and skilled personnel (6%). Completion rates of the referral forms were as follows: < 50% completion (n = 81; 37.3%), 50-75% completion (n = 112; 51.6%) above 75% completion (n = 24; 11.1%). Some of the handwriting were not legible and were quite difficult to read. The key informants stated that incomplete forms sometimes delay treatment. The head of the antenatal care unit at the referral hospital suggested professional development sessions as a strategy for supporting clinicians to fill the forms as expected. CONCLUSION: The Ghana Health Service should conduct regular audits, develop job aides and provide incentives for health professionals who accurately complete referral forms. Completing forms and digitizing health records can help ensure further efficiencies in the health information system and sustain good maternity referral documentation practices.