Ultrasound assessment of malnutrition in infancy: a pilot case-control study.

This study aimed at determining the intra- and inter-rater reliability in ultrasound body composition measurements and investigating the differences between malnourished and non-malnourished infants. Sonographic images for measurements of fat and muscle thickness were compared between 9 malnourished and 9 non-malnourished hospitalized infants. The mean of fat and muscle thickness sums were 12.44 ± 7.58 mm and 28.98 ± 7.18 mm, respectively. The intra- and inter-rater intraclass correlation coefficient were above 0.9 for both measurements, indicating high intra- and inter-rater reliability. Compared to non-malnourished infants, malnourished infants have 45% of fat thickness sum and 71% of muscle thickness sum. Ultrasound measurements of body composition in infants were different between hospitalized malnourished and non-malnourished infants. This approach has the potential to be utilized more broadly, from assessing the nutritional status of critically ill infants in intensive care units to screening for malnutrition in high-risk infant populations.

MRI-Based Brain Volume Scoring in Cerebral Malaria Is Externally Valid and Applicable to Lower-Resolution Images.

BACKGROUND AND PURPOSE: Children with cerebral malaria have an elevated risk of mortality and neurologic morbidity. Both mortality and morbidity are associated with initially increased brain volume on MR imaging, as graded by the Brain Volume Score, a subjective ordinal rating scale created specifically for brain MRIs in children with cerebral malaria. For the Brain Volume Score to be more widely clinically useful, we aimed to determine its independent reproducibility and whether it can be applicable to lower-resolution MRIs. MATERIALS AND METHODS: To assess the independent reproducibility of the Brain Volume Score, radiologists not associated with the initial study were trained to score MRIs from a new cohort of patients with cerebral malaria. These scores were then compared with survival and neurologic outcomes. To assess the applicability to lower-resolution MRI, we assigned Brain Volume Scores to brain MRIs degraded to simulate a very-low-field (64 mT) portable scanner and compared these with the original scores assigned to the original nondegraded MRIs. RESULTS: Brain Volume Scores on the new cohort of patients with cerebral malaria were highly associated with outcomes (OR for mortality = 16, P < .001). Scoring of the simulated degraded images remained consistent with the Brain Volume Scores assigned to the original higher-quality (0.35 T) images (intraclass coefficients > 0.86). CONCLUSIONS: Our findings demonstrate that the Brain Volume Score is externally valid in reproducibly predicting outcomes and can be reliably assigned to lower-resolution images.

Cerebral Metabolic Crisis in Pediatric Cerebral Malaria.

Cerebral metabolic energy crisis (CMEC), often defined as a cerebrospinal fluid (CSF) lactate: pyruvate ratio (LPR) >40, occurs in various diseases and is associated with poor neurologic outcomes. Cerebral malaria (CM) causes significant mortality and neurodisability in children worldwide. Multiple factors that could lead to CMEC are plausible in these patients, but its frequency has not been explored. Fifty-three children with CM were enrolled and underwent analysis of CSF lactate and pyruvate levels. All 53 patients met criteria for a CMEC (median CSF LPR of 72.9 [interquartile range [IQR]: 58.5-93.3]). Half of children met criteria for an ischemic CMEC (median LPR of 85 [IQR: 73-184]) and half met criteria for a nonischemic CMEC (median LPR of 60 [IQR: 54-79]. Children also underwent transcranial doppler ultrasound investigation. Cerebral blood flow velocities were more likely to meet diagnostic criteria for low flow (<2 standard deviation from normal) or vasospasm in children with an ischemic CMEC (73%) than in children with a nonischemic CMEC (20%, p = 0.04). Children with an ischemic CMEC had poorer outcomes (pediatric cerebral performance category of 3-6) than those with a nonischemic CMEC (46 vs. 22%, p = 0.03). CMEC was ubiquitous in this patient population and the processes underlying the two subtypes (ischemic and nonischemic) may represent targets for future adjunctive therapies.

Automated analysis of low-field brain MRI in cerebral malaria.

A central challenge of medical imaging studies is to extract biomarkers that characterize disease pathology or outcomes. Modern automated approaches have found tremendous success in high-resolution, high-quality magnetic resonance images. These methods, however, may not translate to low-resolution images acquired on magnetic resonance imaging (MRI) scanners with lower magnetic field strength. In low-resource settings where low-field scanners are more common and there is a shortage of radiologists to manually interpret MRI scans, it is critical to develop automated methods that can augment or replace manual interpretation, while accommodating reduced image quality. We present a fully automated framework for translating radiological diagnostic criteria into image-based biomarkers, inspired by a project in which children with cerebral malaria (CM) were imaged using low-field 0.35 Tesla MRI. We integrate multiatlas label fusion, which leverages high-resolution images from another sample as prior spatial information, with parametric Gaussian hidden Markov models based on image intensities, to create a robust method for determining ventricular cerebrospinal fluid volume. We also propose normalized image intensity and texture measurements to determine the loss of gray-to-white matter tissue differentiation and sulcal effacement. These integrated biomarkers have excellent classification performance for determining severe brain swelling due to CM.

Prospective cohort study to identify prevalence, risk factors and outcomes of infection associated kidney disease in a regional hospital in Malawi.

OBJECTIVES: Acute kidney injury (AKI) is a common and severe complication of community acquired infection, but data on impact in sub-Saharan Africa (SSA) are lacking. We determined prevalence, risk factors and outcomes of infection associated kidney disease in adults in Malawi. DESIGN: A prospective cohort study of adults admitted to hospital with infection, from February 2021 to June 2021, collecting demographic, clinical, laboratory and ultrasonography data. SETTING: Adults admitted to a regional hospital in Southern Region, Malawi. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were prevalence of kidney disease and mortality by Cox proportional hazard model. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes were risk factors for AKI identified by logistic regression and prevalence of chronic kidney disease at 3 months. RESULTS: We recruited 101 patients presenting to hospital with infection. Median age was 38 years (IQR: 29-48 years), 88 had known HIV status of which 53 (60%) were living with HIV, and of these 42 (79%) were receiving antiretroviral therapy. AKI was present in 33/101 at baseline, of which 18/33 (55%) cases were severe (KDIGO stage 3). At 3 months, 28/94 (30%) participants had died, while 7/61 (11%) of survivors had chronic kidney disease. AKI was associated with older age (age: 60 years vs 40 years, OR: 3.88, 95% CI 1.82 to 16.64), and HIV positivity (OR: 4.08, 95% CI 1.28 to 15.67). Living with HIV was independently associated with death (HR: 3.97, 95% CI 1.07 to 14.69). CONCLUSIONS: Kidney disease is common among hospitalised adults with infection in Malawi, with significant kidney impairment identified at 3 months. Our study highlights the difficulty in diagnosing acute and chronic kidney disease, and the need for more accurate methods than creatinine based estimated glomerular filtration rate (eGFR) equations for populations in Africa. Patients with kidney impairment identified in hospital should be prioritised for follow-up.

Mechanisms of Transcranial Doppler Ultrasound phenotypes in paediatric cerebral malaria remain elusive.

BACKGROUND: Cerebral malaria (CM) results in significant paediatric death and neurodisability in sub-Saharan Africa. Several different alterations to typical Transcranial Doppler Ultrasound (TCD) flow velocities and waveforms in CM have been described, but mechanistic contributors to these abnormalities are unknown. If identified, targeted, TCD-guided adjunctive therapy in CM may improve outcomes. METHODS: This was a prospective, observational study of children 6 months to 12 years with CM in Blantyre, Malawi recruited between January 2018 and June 2021. Medical history, physical examination, laboratory analysis, electroencephalogram, and magnetic resonance imaging were undertaken on presentation. Admission TCD results determined phenotypic grouping following a priori definitions. Evaluation of the relationship between haemodynamic, metabolic, or intracranial perturbations that lead to these observed phenotypes in other diseases was undertaken. Neurological outcomes at hospital discharge were evaluated using the Paediatric Cerebral Performance Categorization (PCPC) score. RESULTS: One hundred seventy-four patients were enrolled. Seven (4%) had a normal TCD examination, 57 (33%) met criteria for hyperaemia, 50 (29%) for low flow, 14 (8%) for microvascular obstruction, 11 (6%) for vasospasm, and 35 (20%) for isolated posterior circulation high flow. A lower cardiac index (CI) and higher systemic vascular resistive index (SVRI) were present in those with low flow than other groups (p < 0.003), though these values are normal for age (CI 4.4 [3.7,5] l/min/m2, SVRI 1552 [1197,1961] dscm-5m2). Other parameters were largely not significantly different between phenotypes. Overall, 118 children (68%) had a good neurological outcome. Twenty-three (13%) died, and 33 (19%) had neurological deficits. Outcomes were best for participants with hyperaemia and isolated posterior high flow (PCPC 1-2 in 77 and 89% respectively). Participants with low flow had the least likelihood of a good outcome (PCPC 1-2 in 42%) (p < 0.001). Cerebral autoregulation was significantly better in children with good outcome (transient hyperemic response ratio (THRR) 1.12 [1.04,1.2]) compared to a poor outcome (THRR 1.05 [0.98,1.02], p = 0.05). CONCLUSIONS: Common pathophysiological mechanisms leading to TCD phenotypes in non-malarial illness are not causative in children with CM. Alternative mechanistic contributors, including mechanical factors of the cerebrovasculature and biologically active regulators of vascular tone should be explored.

A clinical and molecular epidemiological survey of hepatitis C in Blantyre, Malawi, suggests a historic mechanism of transmission.

Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. There are no previous representative community HCV prevalence studies from Southern Africa, and limited genotypic data. Epidemiological data are required to inform an effective public health response. We conducted a household census-based random sampling serological survey, and a prospective hospital-based study of patients with cirrhosis and hepatocellular carcinoma (HCC) in Blantyre, Malawi. We tested participants with an HCV antigen/antibody ELISA (Monolisa, Bio-Rad), confirmed with PCR (GeneXpert, Cepheid) and used line immunoassay (Inno-LIA, Fujiribio) for RNA-negative participants. We did target-enrichment whole-genome HCV sequencing (NextSeq, Illumina). Among 96,386 censused individuals, we randomly selected 1661 people aged ≥16 years. Population-standardized HCV RNA prevalence was 0.2% (95% CI 0.1-0.5). Among 236 patients with cirrhosis and HCC, HCV RNA prevalence was 1.9% and 5.0%, respectively. Mapping showed that HCV RNA+ patients were from peri-urban areas surrounding Blantyre. Community and hospital HCV RNA+ participants were older than comparator HCV RNA-negative populations (median 53 vs 30 years for community, p = 0.01 and 68 vs 40 years for cirrhosis/HCC, p < 0.001). Endemic HCV genotypes (n = 10) were 4v (50%), 4r (30%) and 4w (10%). In this first census-based community serological study in Southern Africa, HCV was uncommon in the general population, was centred on peri-urban regions and was attributable for <5% of liver disease. HCV infection was observed only among older people, suggesting a historic mechanism of transmission. Genotype 4r, which has been associated with treatment failure with ledipasvir and daclatasvir, is endemic.

Ultrasound appearance of the kidney among radiology department attendees of a tertiary centre in Malawi.

Background: Diagnostic and therapeutic decisions in nephrology in low-resource settings are frequently based on ultrasound assessment of kidney size. An understanding of reference values is critical, particularly given the rise of non-communicable disease and the expanding availability of point-of-care ultrasound. However, there is a paucity of normative data from African populations. We determined estimates of kidney ultrasound measures, including kidney size based on age, sex, and HIV status, among apparently healthy outpatient attendees of Queen Elizabeth Central hospital radiology department, Blantyre, Malawi. Methods: We performed a cross-sectional cohort study of 320 adults attending the radiology department between October 2021 and January 2022. Bilateral kidney ultrasound was performed on all participants using a portable Mindray DP-50 machine and a 5MHz convex probe. The sample was stratified by age, sex, and HIV status. Predictive linear modelling was used to construct reference ranges for kidney size estimating the central 95 percentiles of 252 healthy adults. Exclusion criteria for the healthy sample were known kidney disease, hypertension, diabetes, BMI > 35, heavy alcohol intake, smoking and ultrasonographic abnormalities. Results: There were 162/320 (51%) male participants. The median age was 47 (interquartile range [IQR] 34-59). Among people living with HIV 134/138 (97%) were receiving antiretroviral therapy. Men had larger average kidney sizes: mean 9.68 cm (SD 0.80 cm), compared to 9.46 cm (SD 0.87 cm) in women ( p = 0.01). Average kidney sizes in people living with HIV were not significantly different from those who were HIV-negative, 9.73 cm (SD 0.93 cm) versus 9.58 cm (SD 0.93 cm) ( p = 0.63). Conclusions: This is the first report of the apparently healthy kidney size in Malawi. Predicted kidney size ranges may be used for reference in the clinical assessment of kidney disease in Malawi.

The Role of Human Immunodeficiency Virus-Associated Vasculopathy in the Etiology of Stroke.

Background: Human immunodeficiency virus (HIV) infection is a recognized risk factor for stroke among young populations, but the exact mechanisms are poorly understood. We studied the clinical, radiologic, and histologic features of HIV-related ischemic stroke to gain insight into the disease mechanisms. Methods: We conducted a prospective, in-depth analysis of adult ischemic stroke patients presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, in 2011. Results: We recruited 64 HIV-infected and 107 HIV-uninfected patients. Those with HIV were significantly younger (P < .001) and less likely to have established vascular risk factors. Patients with HIV were more likely to have large artery disease (21% vs 10%; P < .001). The commonest etiology was HIV-associated vasculopathy (24 [38%]), followed by opportunistic infections (16 [25%]). Sixteen of 64 (25%) had a stroke soon after starting antiretroviral therapy (ART), suggesting an immune reconstitution-like syndrome. In this group, CD4+ T-lymphocyte count was low, despite a significantly lower HIV viral load in those recently started on treatment (P < .001). Conclusions: HIV-associated vasculopathy and opportunistic infections are common causes of HIV-related ischemic stroke. Furthermore, subtypes of HIV-associated vasculopathy may manifest as a result of an immune reconstitution-like syndrome after starting ART. A better understanding of this mechanism may point toward new treatments.

Cyst-like change in the thyroid cartilage: A developmental variant in children.

Neck sonography is frequently encountered on ultrasound lists in the paediatric patient population. Anecdotally, one of the most frequent clinical indications is the investigation of a neck lump. While performing an ultrasound of the neck, structures other than those routinely assessed, such as the thyroid cartilage and mandibular cortex also come into view. Occasionally, pathology in these structures is also encountered, albeit less frequently. The purpose of this case report and review is to illustrate the ultrasound, computed tomography and magnetic resonance imaging appearances of cyst-like changes in the thyroid cartilage that are encountered in children, particularly in early adolescence.

The internal acoustic canal--another review area in paediatric sensorineural hearing loss.

Morphological abnormalities of the internal acoustic canal (IAC), albeit rare, are sometimes associated with hearing loss in children. We present an illustration of the spectrum of IAC abnormalities together with a brief review of the embryology and anatomy of the IAC and the techniques used when imaging the petrous temporal bone. This review focuses on morphological abnormalities of the IAC together with their clinical implications and impact on clinical management.

Teleradiology usage and user satisfaction with the telemedicine system operated by médecins sans frontières.

Médecins Sans Frontières (MSF) began a pilot trial of store-and-forward telemedicine in 2010, initially operating separate networks in English, French, and Spanish; these were merged into a single, multilingual platform in 2013. We reviewed the pattern of teleradiology usage on the MSF telemedicine platform in the 4-year period from April 2010. In total, 564 teleradiology cases were submitted from 22 different countries. A total of 1114 files were uploaded with the 564 cases, the majority being of type JPEG (n = 1081, 97%). The median file size was 938 kb (interquartile range, IQR 163-1659). A panel of 14 radiologists was available to report cases, but most (90%) were reported by only 4 radiologists. The median radiologist response time was 6.1 h (IQR 3.0-20). A user satisfaction survey was sent to 29 users in the last 6 months of the study. There was a 28% response rate. Most respondents found the radiologist's advice helpful and all of them stated that the advice assisted in clarification of a diagnosis. Although some MSF sites made substantial use of the system for teleradiology, there is considerable potential for expansion. More promotion of telemedicine may be needed at different levels of the organization to increase engagement of staff.

Mid-term outcomes for Endoscopic versus Open Vein Harvest: a case control study.

BACKGROUND: Saphenous vein remains the most common conduit for coronary artery bypass grafting with increasing uptake of minimally invasive harvesting techniques. While Endoscopic Vein Harvest (EVH) has been demonstrated to improve early morbidity compared to Open Vein Harvest (OVH), recent literature suggests that this may be at the expense of graft patency at one year and survival at three years. METHODS: We undertook a retrospective single-centre, single-surgeon, case-control study of EVH (n = 89) and OVH (n = 182). The primary endpoint was death with secondary endpoints including acute coronary syndrome, revascularisation or other major adverse cardiac events. Freedom from angina, wound complications and self-rated health status were also assessed. Where repeat angiography had been performed, this was reviewed. RESULTS: Both groups were well matched demographically and for peri-operative characteristics. All cause mortality was 2/89 (2%) and 11/182 (6%) in the EVH and OVH groups respectively. This was shown by Cox Log-Rank analysis to be non-significant (p = 0.65), even if adjusting for inpatient mortality (p = 0.74). There was no difference in the rates of freedom from angina (p = 1.00), re-admission (p = 0.78) or need for further anti-anginals (p = 1.00). There was a significant reduction in the incidence of leg wound infections and complications in the endoscopic group (EVH: 7%; OVH: 28%; p = 0.0008) and the skew of high patient self-rated health scores in the EVH group (61% compared to 52% in the open group) approached statistical significance (p = 0.06). CONCLUSIONS: While aware of the limitations of this small retrospective study, we are heartened by the preliminary results and consider our data to be justification for continuing to provide patients the opportunity to have minimally invasive conduit harvest in our centre. More robust evidence is still required to elucidate the implications of endoscopic techniques on conduit patency and patient outcome, but until the results of a large, prospective and randomised trial are available, we believe we can confidently offer our patients the option and benefits of EVH.

Massive hemothorax secondary to metastatic renal carcinoma.

We present the case of a 78-year-old man with a past history of nephrectomy for renal cell carcinoma who was brought to the emergency room in hypovolemic shock after suddenly collapsing at home. A chest roentgenogram taken on admission showed a large pleural effusion on the right with a mediastinal shift to the left. A contrast computed tomographic scan of his chest excluded aortic dissection. An emergency right thoracotomy was performed, which revealed a chest wall tumor that was bleeding profusely. The tumor was biopsied after the bleeding was controlled. The histologic report revealed metastatic renal cell carcinoma, which is a rare cause for a spontaneous massive hemothorax.