Derivation of decision rules to predict clinically important outcomes in acute flank pain patients

Objective

Routine CT for patients with acute flank pain has not been shown to improve patient outcomes, and it may unnecessarily expose patients to radiation and increased costs. As preliminary steps toward the development of a guideline for selective CT, we sought to determine the prevalence of clinically important outcomes in patients with acute flank pain and derive preliminary decision rules.

Imaging-Guided Core Biopsy of the Breast

Abstract: This article reports on our experience with core needle biopsy (CNB) of the breast and presents a review of the literature. We have performed CNB on 304 women with abnormalities classified on imaging as highly suggestive of malignancy (52 cases), suspicious (245 cases) or probably benign (7 cases). The CNB procedure was performed using either stereotactic mammographic guidance (251 cases) or ultrasound guidance (53 cases) with a 14-gauge needle. At least five specimens were obtained for each abnormality. The sensitivity of core biopsy was 98% and the specificity was 99%. There were three false negatives and one false positive. An excisional biopsy was recommended in 17 cases in which the CNB diagnosis was not definitive, including 12 with atypical ductal hyperplasia (ADH), 4 with discordance between imaging and histologic results, and 1 with inconclusive histology. Our results are consistent with other reports in the literature using 14-gauge core needle biopsy. In our practice, core biopsy has proven to be an effective method for the evaluation of imaging findings that are suspicious or highly suggestive of malignancy.     

Maternal mortality in rural Bangladesh: the Jamalpur District

During the 12-month period from September 1982 to August 1983, 9,317 live births and 58 maternal deaths were recorded in Melanda and Islampur upazilas in the Jamalpur district of rural Bangladesh, giving a maternal mortality rate of 62.3 per 10,000 live births. Maternal mortality was positively related to maternal age and parity, with the mortality risk rising very sharply beyond age 35 years, and beyond parity four among women aged 25-34 years in particular. The most common causes of maternal death were eclampsia (20.7 percent), septic abortion (20.7 percent), postpartum sepsis (10.3 percent), obstructed labor (10.3 percent), and antepartum and postpartum hemorrhage (10.3 percent). These findings indicate that family planning, by decreasing the likelihood of pregnancy after age 35 and parity four, can help reduce the proportion of women at risk of maternal mortality.     

Bull horn injuries

Bull horn injury is not uncommon, and during a 12 year period from 1977 to 1988, 101 patients required inpatient treatment at the Christian Medical College Hospital, a teaching hospital at Vellore in South India. The ages of these patients ranged from two years to 90 years and the male to female ratio was 4:1. Sixty-one per cent of the injuries occurred either to the perineum or abdomen and wounds were directed obliquely upward. Thirty-five per cent required extensive surgical intervention. The over-all wound infection rate was 12.9 per cent. Of wounds that were primarily closed, 42.9 per cent had wound infection, while only 6.3 per cent that were secondarily closed developed infection. Two patients died as a consequence of the injury. Based on the results of this study, we recommend that a careful evaluation of the injury and timely and appropriate management of each patient must be done to reduce morbidity and mortality. Primary closure of wounds must be avoided even when surgical intervention is possible soon after injury.     

Palliative Care Utilization Among Non-Western Migrants in Europe: A Systematic Review

The paper aims to identify and describe the European evidence on opportunities and barriers to access and utilization of palliative care among non- western migrants. A systematic review in accordance with PRISMA guidelines was conducted in June 2020, searching Medline, CINAHL, PsychINFO and EMBASE databases. PROSPERO# CRD42020193651. Studies included empirical research published between 2011 and 2020. Search words were, for example, ethnic groups and palliative care. Thematic analysis was used to analyze data. Twenty nine qualitative and six quantitative studies were included. Four main themes were identified: communication and language; knowledge and awareness; patient preferences, cultural and religious issues; and lack of resources at different levels of palliative care service provision. Migrants’ access to palliative care is impeded at system, community and individual levels, yet, recommendations are mostly at the individual level. Closer attention is required to these different levels when designing future palliative interventions for migrants.

     

Adjuvant Chemotherapy Guided by Molecular Profiling and Improved Outcomes in Early Stage,Non–Small-Cell Lung Cancer

Introduction

Many early stage non–small-cell lung cancer (NSCLC) patients who are not considered candidates for adjuvant treatment according to current guidelines do harbor occult metastasis, and have disease recurrence despite complete resection. Although National Comprehensive Cancer Network (NCCN) guidelines suggest clinicopathologic characteristics to identify high-risk patients for adjuvant intervention, molecular profiling more accurately predicts 5-year survival. Early evidence of clinical benefit from application of this molecular-based management strategy, however, has not been reported.

Accounts of severe acute obstetric complications in Rural Bangladesh

Background

Obstetric fistula is a physically and socially disabling obstetric complication that affects about 3,000 women in Tanzania every year. The fistula, an opening that forms between the vagina and the bladder and/or the rectum, is most frequently caused by unattended prolonged labour, often associated with delays in seeking and receiving appropriate and adequate birth care. Using the availability, accessibility, acceptability and quality of care (AAAQ) concept and the three delays model, this article provides empirical knowledge on birth care experiences of women who developed fistula after prolonged labour.

Methods

We used a mixed methods approach to explore the birthing experiences of women affected by fistula and the barriers to access adequate care during labour and delivery. Sixteen women were interviewed for the qualitative study and 151 women were included in the quantitative survey. All women were interviewed at the Comprehensive Community Based Rehabilitation Tanzania in Dar es Salaam and Bugando Medical Centre in Mwanza.

Results

Women experienced delays both before and after arriving at a health facility. Decisions on where to seek care were most often taken by husbands and mothers-in-law (60%). Access to health facilities providing emergency obstetric care was inadequate and transport was a major obstacle. About 20% reported that they had walked or were carried to the health facility. More than 50% had reported to a health facility after two or more days of labour at home. After arrival at a health facility women experienced lack of supportive care, neglect, poor assessment of labour and lack of supervision. Their birth accounts suggest unskilled birth care and poor referral routines.

Conclusions

This study reveals major gaps in access to and provision of emergency obstetric care. It illustrates how poor quality of care at health facilities contributes to delays that lead to severe birth injuries, highlighting the need to ensure women's rights to accessible, acceptable and adequate quality services during labour and delivery.     

Tropism of SARS-CoV-2 for human cortical astrocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, accompany as many as one-third of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized stem-cell-derived cortical organoids as well as primary human cortical tissue, both from developmental and adult stages. We find significant and predominant infection in cortical astrocytes in both primary tissue and organoid cultures, with minimal infection of other cortical populations. Infected and bystander astrocytes have a corresponding increase in inflammatory gene expression, reactivity characteristics, increased cytokine and growth factor signaling, and cellular stress. Although human cortical cells, particularly astrocytes, have no observable ACE2 expression, we find high levels of coronavirus coreceptors in infected astrocytes, including CD147 and DPP4. Decreasing coreceptor abundance and activity reduces overall infection rate, and increasing expression is sufficient to promote infection. Thus, we find tropism of SARS-CoV-2 for human astrocytes resulting in inflammatory gliosis-type injury that is dependent on coronavirus coreceptors.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the life-threatening illness COVID-19 and is responsible for a global pandemic resulting in more than 5.8 million deaths worldwide. Although SARS-CoV-2 infection can cause catastrophic, life-threatening damage to respiratory function, the capacity to infect other cell types and disrupt function of additional organ systems is a subject of intense study. Strikingly, many patients suffering with or having recovered from COVID-19 present with a range of neurological symptoms including seizures; encephalopathy; stroke; headaches; dizziness; short-term memory loss; loss of smell and taste; confusion; a general inability to focus; and new or recurring neuropsychiatric symptoms, like anxiety and depression (1–5). As many as one-third of individuals, 6 mo after recovering from COVID-19 infection, are diagnosed with neurological or neuropsychiatric conditions (6). Additionally, individuals with mental health diagnoses are more susceptible to coronavirus infection and have impaired long-term health outcomes (7).It is unclear whether the range of neurological symptoms are a result of direct infection of the neural tissue or a secondary consequence of widespread inflammation downstream of viral infection in other tissues. Several studies have demonstrated how inflammation contributes to systemic problems in a variety of organ systems, including the central nervous system (CNS) (8, 9). However, SARS-CoV-2 can infect neurons in the nasal epithelium, a potential mode of entry to the CNS from the periphery, and the presence of viral RNA has been detected in neural tissues in patients (10). Recent studies report mixed findings regarding the presence of coronavirus viral RNA and antibodies in the cerebral spinal fluid (CSF) of COVID-19 patients (3, 8, 11, 12). However, choroid plexus organoids containing the cell type that produces CSF can be readily infected by SARS-CoV-2 in vitro (13, 14), suggesting possible viral access to CSF. Additionally, the virus can infect and disrupt brain vasculature. Studies of postmortem brain tissue from severely infected COVID-19 patients have reported widespread inflammation in the brainstem, choroid plexus, and brain parenchyma characterized by infiltration of immune cells including microglia and T cells, as well as infection of cranial nerves, microvascular injury, fibrinogen leakage, and extensive astrogliosis (8, 15, 16). Together, these studies suggest the capacity for viral transmission into the CNS through leaky vasculature, the nasal epithelium, and/or CSF.The vulnerability of particular cell types in the brain and the impact on neurological health and function require in-depth study, and human stem-cell-derived neural models have been utilized to evaluate viral tropism (17, 18). Studies of cerebral organoids, which are reflective of developmental stages, suggest that in vitro neurons may be vulnerable to SARS-CoV-2 infection. However, reports regarding susceptibility of neurons from different brain regions have been mixed across organoid studies (13, 14, 19). Recently, studies have begun to explore the vulnerability of nonneuronal populations, including vascular pericytes and glial cells, using stem-cell-derived organoid and assembloid models (20, 21). Additionally, studies exploring the loss of smell identified viral tropism of nonneural support cells and vascular cells in the olfactory epithelium (22). Here, we utilized primary cortical tissue from both the developing and the adult brain, paired with cortical organoid models across neurogenic and gliogenic stages, to evaluate which human neural cell types can be directly infected by SARS-CoV-2 and at what stages of maturation. In primary cortical tissue cultures and cortical organoids exposed to SARS-CoV-2, we observed significant infection and viral replication in immature and mature astrocytes but minimal infection in other neural cell types. As a response to infection, we observed widespread inflammation, cytokine secretion, and reactivity in astrocytes. However, cortical astrocytes do not express observable levels of ACE2, the canonical SARS-CoV-2 receptor, suggesting that the virus may use another means of entry. We observed that SARS-CoV-2 cofactors CD147 and DPP4 are highly expressed in infected astrocytes. Reducing the abundance of CD147 or the activity of DPP4 reduced infection, whereas increasing expression of these receptors promoted infection, suggesting a role in viral entry or propagation. Our study provides evidence of SARS-CoV-2 tropism for human astrocytes with implications for the cellular vulnerability of the human brain and downstream consequences to neurological function.     

Clinical Epidemiology,Pathology, and Molecular Investigation of Lumpy Skin Disease Outbreaks in Bangladesh during 2020–2021 Indicate the Re-Emergence of an Old African Strain

Lumpy skin disease (LSD) emerged in Bangladesh in mid-2019, leading to great economic losses for cattle farmers. This study describes the recent occurrence of the LSDV in Bangladesh and examines the clinical manifestation of the disease in local cattle breeds, characteristic epidemiological features, and pathological findings in affected animals. In addition, a full-genome sequencing of two local LSDV isolates was carried out. A total of 565 animals from 88 households were investigated, and 165 samples (skin lesions, saliva, nasal discharge, feces, and milk) were collected for virus detection. Pathology and immunohistochemistry were performed on nodule biopsies. Fever, nodular skin lesions, and swelling of the joints were the most common clinical manifestations. Skin lesions had a higher concentration of viral DNA compared to other sample types and were therefore selected for virus isolation and characterization. Pathology of the LSD skin nodules comprised a granulomatous reaction in the dermis and hypodermis that extended to the surrounding tissues. Development of the skin lesions started with swelling of keratinocytes with cytoplasmic vacuolation, vasculitis, panniculitis, thrombosis, and infarction. Altogether, the LSDV produced transmural, hemorrhagic, necrotizing, proliferative and ulcerative dermatitis. The LSD viral antigen was detected occasionally in the macrophages, epithelial cells, and vascular smooth muscle cells. The complete genome sequence analysis revealed that the two Bangladeshi field strains (BD-V392.1 and BD-V395.1) were distinct from the contemporary field strains and were closely related to the ancestral African Neethling strain. The findings of this study will improve the diagnosis, monitoring, and control of LSD in Bangladesh.