Hyperphosphatemia and its relationship with blood pressure, vasoconstriction, and endothelial cell dysfunction in hypertensive hemodialysis patients.

BACKGROUND: Hyperphosphatemia occurs frequently in end-stage renal disease patients on hemodialysis and is associated with increased mortality. Hyperphosphatemia contributes to vascular calcification in these patients, but there is emerging evidence that it is also associated with endothelial cell dysfunction. METHODS: We conducted a cross-sectional study in hypertensive hemodialysis patients. We obtained pre-hemodialysis measurements of total peripheral resistance index (TPRI, non-invasive cardiac output monitor) and plasma levels of endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA). We ascertained the routine peridialytic blood pressure (BP) measurements from that treatment and the most recent pre-hemodialysis serum phosphate levels. We used generalized linear regression analyses to determine independent associations between serum phosphate with BP, TPRI, ET-1, and ADMA while controlling for demographic variables, parathyroid hormone (PTH), and interdialytic weight gain. RESULTS: There were 54 patients analyzed. Mean pre-HD supine and seated systolic and diastolic BP were 164 (27), 158 (21), 91.5 (17), and 86.1 (16) mmHg. Mean serum phosphate was 5.89 (1.8) mg/dL. There were significant correlations between phosphate with all pre-hemodialysis BP measurements (r = 0.3, p = .04; r = 0.4, p = .002; r = 0.5, p < .0001; and r = 0.5, p = .0003.) The correlations with phosphate and TPRI, ET-1, and ADMA were 0.3 (p = .01), 0.4 (p = .007), and 0.3 (p = .04). In our final linear regression analyses controlling for baseline characteristics, PTH, and interdialytic weight gain, independent associations between phosphate with pre-hemodialysis diastolic BP, TPRI, and ET-1 were retained (ß = 4.33, p = .0002; log transformed ß = 0.05, p = .005; reciprocal transformed ß = -0.03, p = .047). CONCLUSIONS: Serum phosphate concentration is independently associated with higher pre-HD BP, vasoconstriction, and markers of endothelial cell dysfunction. These findings demonstrate an additional negative impact of hyperphosphatemia on cardiovascular health beyond vascular calcification. TRIAL REGISTRATION: The study was part of a registered clinical trial, NCT01862497 (May 24, 2013).

Decompressive Craniectomy for Pediatric Traumatic Brain Injury in Low-and-Middle Income and High Income Countries.

Traumatic brain injury is one of the leading causes of mortality and morbidity in children worldwide. In severe cases, high intracranial pressure is the most frequent cause of death. When first-line medical management fails, the neurosurgical procedure of decompressive craniectomy (DC) has been proposed for controlling intracranial pressure and improving the long-term outcomes for children with severe traumatic brain injury. However, the use of this procedure is controversial. The evidence from clinical trials shows some promise for the use of DC as an effective second-line treatment. However, it is limited by conflicting trial results, a lack of trials, and a high risk of bias. Furthermore, most research comes from retrospective observational studies and case series. This narrative review considers the strength of evidence for the use of DC in both a high income country and low-and-middle income country setting and examine how we can improve study design to better assess the efficacy of this procedure and increase the clinical translatability of results to centers worldwide. Specifically, we argue for a need for further studies with higher pediatric participant numbers, multicenter collaboration, and the use of a more consistent methodology to enable comparability of results among settings.

The associations between orthostatic blood pressure changes and extracellular volume in hemodialysis patients.

INTRODUCTION: Extracellular volume (ECV) predicts mortality in hemodialysis patients, but it is difficult to assess clinically. Peridialytic blood pressure (BP) measurements can help ECV assessment. Orthostatic BP is routinely measured clinically, but its association with ECV is unknown. METHODS: In a cohort of hypertensive hemodialysis patients, we measured posthemodialysis ECV/weight with bioimpedance spectroscopy and analyzed its association with post-HD orthostatic BP measurements obtained during routine care. Using linear and logistic regression, the primary outcomes were orthostatic BP change and orthostatic hypotension (OH) defined by systolic BP decrease of at least 20 mmHg or diastolic decrease of at least 10 mmHg. Model 1 controlled for sex, age, and diabetes. Model 2 additionally controlled for ultrafiltration rate and antihypertensive medications. We conducted sensitivity analysis using OH definition of systolic BP decrease of at least 30 mmHg. FINDINGS: Among 57 participants, mean orthostatic systolic BP change was -7.30 (20) mmHg and mean ECV/weight was 0.24 (0.04) L/kg. Post-HD ECV/weight was not associated with orthostatic systolic BP change (ß = 8.2, p = 0.6). There were 16 participants with and 41 participants without OH. The ECV/weight did not differ between these groups (0.22 [0.04] vs. 0.24 [0.05] L/Kg, p = 0.09) and did not predict OH in logistic regression (OR 11, 4.04; 95% CI 0.2-671, 0.03-0.530 in the two models.) In a sensitivity analysis, ECV/weight was lower in the OH group (0.22 [0.03] vs. 0.25 [0.04] L/kg, p = 0.005), but this was accompanied by differences in sex and diabetes. Using logistic regression, there was no independent association between ECV/weight with OH. DISCUSSION: Orthostatic systolic BP change after HD completion is not a reliable indicator of posthemodialysis ECV. When considering other factors associated with orthostatic BP, ECV/weight is not independently associated with OH. Although transient postdialytic differences in intravascular volume may be associated with OH, posthemodialysis OH does not necessarily indicate ECV depletion.

The effects of extracellular volume and intradialytic peripheral resistance changes on ambulatory blood pressure in hemodialysis patients with and without recurrent intradialytic hypertension.

BACKGROUND: Hypertension and extracellular volume (ECV) overload are interrelated mortality risk factors in hemodialysis (HD) patients, but confounding related to changes in ECV and vasoconstriction during and between treatments obfuscate their relationship. We sought to clarify independent contributions of post-HD ECV and intradialytic changes in vasoconstriction on ambulatory blood pressure (BP) in patients with and without recurrent intradialytic hypertension (IH). METHODS: In this prospective observational study, we obtained measurements of pre- and post-HD ECV with bioimpedance spectroscopy (BIS), pre- and post-HD total peripheral resistance index and 44-h ambulatory BP. Linear regression determined associations between post-HD ECV/weight and intradialytic change in total peripheral resistance index (TPRI) with interdialytic BP and slope. RESULTS: In fully-adjusted models for participants with complete data, post-HD ECV/weight associated with mean ambulatory BP (ß = 133, P = 0.01; n = 52) and ambulatory BP slope (ß = -4.28, P = 0.03; n = 42). ECV/weight was associated with mean ambulatory BP in those with recurrent IH (ß = 314, P = 0.0005; n = 16) and with ambulatory BP slope in those without recurrent IH (ß = -4.56, P = 0.04; n = 28). Interdialytic weight gain percentage and intradialytic TPRI change were not associated with ambulatory BP or slope in any analyses. CONCLUSION: Ambulatory BP in HD patients is more strongly associated with post-HD ECV assessed with BIS than with intradialytic TPRI changes or interdialytic ECV increases. These findings highlight the essential role of recognizing and managing chronic ECV overload to improve ambulatory BP in HD patients, particularly so for those with IH.

Impact of the COVID-19 pandemic on paediatric patients with cancer in low-income, middle-income and high-income countries: protocol for a multicentre, international, observational cohort study.

INTRODUCTION: Childhood cancers are a leading cause of non-communicable disease deaths for children around the world. The COVID-19 pandemic may have impacted on global children's cancer services, which can have consequences for childhood cancer outcomes. The Global Health Research Group on Children's Non-Communicable Diseases is currently undertaking the first international cohort study to determine the variation in paediatric cancer management during the COVID-19 pandemic, and the short-term to medium-term impacts on childhood cancer outcomes. METHODS AND ANALYSIS: This is a multicentre, international cohort study that will use routinely collected hospital data in a deidentified and anonymised form. Patients will be recruited consecutively into the study, with a 12-month follow-up period. Patients will be included if they are below the age of 18 years and undergoing anticancer treatment for the following cancers: acute lymphoblastic leukaemia, Burkitt lymphoma, Hodgkin lymphoma, Wilms tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas and neuroblastomas. Patients must be newly presented or must be undergoing active anticancer treatment from 12 March 2020 to 12 December 2020. The primary objective of the study was to determine all-cause mortality rates of 30 days, 90 days and 12 months. This study will examine the factors that influenced these outcomes. χ2 analysis will be used to compare mortality between low-income and middle-income countries and high-income countries. Multilevel, multivariable logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors. ETHICS AND DISSEMINATION: At the host centre, this study was deemed to be exempt from ethical committee approval due to the use of anonymised registry data. At other centres, participating collaborators have gained local approvals in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for publication in a peer-reviewed journal.

Traumatic Brain Injury-Related Pediatric Mortality and Morbidity in Low- and Middle-Income Countries: A Systematic Review.

BACKGROUND: The burden of pediatric traumatic brain injury (pTBI) in low- and middle-income countries (LMICs) is unknown. To fill this gap, we conducted a review that aimed to characterize the causes of pTBI in LMICs, and their reported associated mortality and morbidity. METHODS: A systematic review was conducted. MEDLINE, Embase, Global Health, and Global Index Medicus were searched from January 2000 to May 2020. Observational or experimental studies on pTBI of individuals aged between 0 and 16 years in LMICs were included. The causes of pTBI and morbidity data were descriptively analyzed, and case fatality rates were calculated. PROSPERO ID: CRD42020171276. RESULTS: A total of 136 studies were included. Fifty-seven studies were at high risk of bias. Of the remaining studies, 170,224 cases of pTBI were reported in 32 LMICs. The odds of having a pTBI were 1.8 times higher (95% confidence interval, 1.6-2.0) in males. The odds of a pTBI being mild were 4.4 times higher (95% confidence interval, 1.9-6.8) than a pTBI being moderate or severe. Road traffic accidents were the most common cause (n = 16,275/41,979; 39%) of pTBIs. On discharge, 24% of patients (n = 4385/17,930) had a reduction in their normal mental or physical function. The median case fatality rate was 7.3 (interquartile range, 2.1-7.7). CONCLUSIONS: Less than a quarter (n = 32) of all LMICs have published high-quality data on the volume and burden of pTBI. From the limited data available, young male children are at a high risk of pTBIs in LMICs, particularly after road traffic accidents.

In vitro comparison of wear characteristics of PyroCarbon and metal on bone: Shoulder hemiarthroplasty.

BACKGROUND: There are concerns regarding glenoid erosion with metal shoulder hemiarthroplasty. PyroCarbon may offer an alternative because of favorable wear characteristics and preservation of the glenoid. The purpose of this study was to assess in vitro bone wear characteristics of PyroCarbon relative to cobalt chromium alloy hemiarthroplasty in a shoulder wear simulator. METHODS: Wear of PyroCarbon and cobalt chromium prostheses articulating with bone were characterized by means of bone wear penetration rate, changes to surface roughness, and wear particle analysis. RESULTS: PyroCarbon prostheses produced significantly less damage to bone and were less damaged by the bone than cobalt chromium prostheses. Cobalt chromium testing was halted at approximately 320,000 cycles because the bone was consumed. Wear testing of PyroCarbon specimens continued through five million cycles. Linearized bone penetration rate, bone volume loss rate, and surface roughness for cobalt chromium test specimens were 30 times greater than for PyroCarbon. CONCLUSIONS: Results demonstrate significantly less damage to bone in simulated shoulder function testing for PyroCarbon hemiarthroplasty implants relative to conventional cobalt chromium implants. Our study supports use of PyroCarbon in humeral head hemiarthroplasty as a viable alternative to conventional metal hemiarthroplasty. Further investigation of PyroCarbon performance in clinical settings is warranted.

Infection and mortality of healthcare workers worldwide from COVID-19: a systematic review.

OBJECTIVES: To estimate COVID-19 infections and deaths in healthcare workers (HCWs) from a global perspective during the early phases of the pandemic. DESIGN: Systematic review. METHODS: Two parallel searches of academic bibliographic databases and grey literature were undertaken until 8 May 2020. Governments were also contacted for further information where possible. There were no restrictions on language, information sources used, publication status and types of sources of evidence. The AACODS checklist or the National Institutes of Health study quality assessment tools were used to appraise each source of evidence. OUTCOME MEASURES: Publication characteristics, country-specific data points, COVID-19-specific data, demographics of affected HCWs and public health measures employed. RESULTS: A total of 152 888 infections and 1413 deaths were reported. Infections were mainly in women (71.6%, n=14 058) and nurses (38.6%, n=10 706), but deaths were mainly in men (70.8%, n=550) and doctors (51.4%, n=525). Limited data suggested that general practitioners and mental health nurses were the highest risk specialities for deaths. There were 37.2 deaths reported per 100 infections for HCWs aged over 70 years. Europe had the highest absolute numbers of reported infections (119 628) and deaths (712), but the Eastern Mediterranean region had the highest number of reported deaths per 100 infections (5.7). CONCLUSIONS: COVID-19 infections and deaths among HCWs follow that of the general population around the world. The reasons for gender and specialty differences require further exploration, as do the low rates reported in Africa and India. Although physicians working in certain specialities may be considered high risk due to exposure to oronasal secretions, the risk to other specialities must not be underestimated. Elderly HCWs may require assigning to less risky settings such as telemedicine or administrative positions. Our pragmatic approach provides general trends, and highlights the need for universal guidelines for testing and reporting of infections in HCWs.

Parsonage Turner syndrome caused by Staphylococcus aureus spondylodiscitis.

Parsonage Turner syndrome (otherwise known as PTS, neuralgic amyotrophy or acute brachial neuritis) is a rare, but clinically significant cause of atraumatic shoulder girdle pain and weakness. Diagnosis is primarily clinical and can be challenging due to its heterogeneous presentation. A case of PTS following systemic infection from Staphylococcus aureus spondylodiscitis is presented. Timely consideration of the diagnosis prevented unnecessary investigation and allowed effective rehabilitation. This is the first case of PTS preceded by S. aureus infection. PTS should be considered in those presenting with acute, atraumatic shoulder dysfunction after systemic infection.

Assessing Extracellular Volume in Hemodialysis Patients Using Intradialytic Blood Pressure Slopes.

BACKGROUND/AIMS: Extracellular volume (ECV) overload is a mortality risk factor in hemodialysis patients, but no standard approach exists to objectively assess this clinically. We aimed to quantify relationships between slopes of repeated intradialytic blood pressure (BP) measurements and ECV. METHODS: In a cross-sectional study of 71 hemodialysis patients, we calculated BP slopes from all intradialytic measurements using Gaussian regression. We measured extracellular and total body water (TBW) with bioimpedance spectroscopy. We analyzed unconditional and conditional associations between BP slope and volume metrics with mixed linear models and sensitivity analyses using non-linear intradialytic BP trajectory. RESULTS: Mean systolic intradialytic BP slope (IBPS) was -0.06 (0.1) mm Hg/min. Post-dialysis extracellular water (ECW)/weight was the volume metric mostly strongly associated with slope (r = 0.34, p = 0.007 for unconditional analysis; ß = 1.45, p = 0.001 for conditional analysis). Among subjects with post-dialysis systolic BP ≥130 mm Hg, the association strengthened (r = 0.40, p = 0.006; ß = 1.42, p = 0.003). ECV was more strongly associated with the BP slope than with pre-dialysis, post-dialysis, or delta systolic BP (r = -0.07, 0.19, 0.28; p = 0.6, 0.1, 0.03). In nonlinear models, BP trajectory also had the strongest association with post-dialysis ECW/body weight (p < 0.001). CONCLUSIONS: In hypertensive hemodialysis patients, measurements of ECV excess are more strongly associated with IBPSs than with pre-dialysis, post-dialysis, or change in systolic BP. Among varying volume metrics, post-dialysis ECW/weight has the strongest association with these slopes. Determining IBPS is a novel method to optimize clinical assessment of ECV in hemodialysis patients.

Special situations: Intradialytic hypertension/chronic hypertension and intradialytic hypotension.

Hypertension is a comorbidity that is present in the majority of end-stage renal disease patients on maintenance hemodialysis. This population is particularly unique because of the dynamic nature of blood pressure (BP) during dialysis. Modest BP decreases are expected in most hemodialysis patients, but intradialytic hypotension and intradialytic hypertension are two special situations that deviate from this as either an exaggerated or paradoxical response to the dialysis procedure. Both of these phenomena are particularly important because they are associated with increased mortality risk compared to patients with modest decreases in BP during dialysis. While the detailed pathophysiology is complex, intradialytic hypotension occurs more often in patients prescribed fast ultrafiltration rates, and reducing this rate is recommended in patients that regularly exhibit this pattern. Patients with intradialytic hypertension have a poorly explained increase in vascular resistance during dialysis, but the consistent associations with extracellular volume overload point toward more aggressive fluid management as the initial management choices for these patients. This up to date review provides the most recent evidence supporting these recommendations as well as the most up to date epidemiologic and mechanistic research studies that have added to this area of dialysis management.

Do trauma courses change practice? A qualitative review of 20 courses in East, Central and Southern Africa.

BACKGROUND: Trauma courses have been shown to improve clinical knowledge and patient outcomes. However, little is known about the individual drivers of change in practice amongst course participants in their home clinic environment. METHODS: Front-line healthcare workers participated in a two-day Primary Trauma Care (PTC) course. Immediately after the course participants completed an evaluation survey on intended change in the management of trauma patients. Six months after the course, participants completed a survey on actual changes that had occurred. RESULTS: A total of 451 participants were sampled, with 321 responding at 6 months, from 40 courses across East, Central and Southern Africa. The most commonly reported intended change was the adoption of an ABCDE/systematic approach (53%). Six months after the course, 92.7% of respondents reported that they had made changes in their management, with adoption of an ABCDE/systematic approach (50.0%) remaining most common. 77% of participants reported an improvement in departmental trauma management, 26% reported an increase in staffing, 29% an increase in equipment and 68% of participants had gone on to train other healthcare workers in PTC. CONCLUSION: The findings suggest that PTC courses not only improve individual management of trauma patients but also but is also associated with beneficial effects for participants' host institutions with regards to staffing, equipment and training.

A Case of Severe Neutropenia From Short-Term Exposure to Moxifloxacin.

Moxifloxacin is commonly prescribed in the inpatient and outpatient management of community-acquired pneumonia and other common infections. We report a case of a 76-year-old man who developed severe neutropenia after several days of treatment for community-acquired pneumonia. The patient had a history of alcohol abuse; however, there were no other offending medications prescribed, and a thorough laboratory workup for other possible causes of neutropenia was negative. The patient's neutrophils and white blood count responded quickly to cessation of fluoroquinolones. This case highlights the importance of identifying patients that might be at high risk for neutropenia that may need closer monitoring on this commonly prescribed medication.

Pathophysiology and implications of intradialytic hypertension.

PURPOSE OF REVIEW: Intradialytic hypertension occurs regularly in 10--15% of hemodialysis patients. A large observational study recently showed that intradialytic hypertension of any magnitude increased mortality risk comparable to the most severe degrees of intradialytic hypotension. The present review review discusses the most recent evidence underlying the pathophysiology of intradialytic hypertension and implications for its management. RECENT FINDINGS: Patients with intradialytic hypertension typically have small interdialytic weight gains, but bioimpedance spectroscopy shows these patients have significant chronic extracellular volume excess. Intradialytic hypertension patients have lower albumin and predialysis urea nitrogen levels, which may contribute to small reductions in osmolarity that prevents blood pressure decreases. Intradialytic vascular resistance surges remain implicated as the driving force for blood pressure increases, but mediators other than endothelin-1 may be responsible. Beyond dry weight reduction, the only controlled intervention shown to interrupt the blood pressure increase is lowering dialysate sodium. SUMMARY: Patients with recurrent intradialytic hypertension should be identified as high-risk patients. Dry weight should be re-evaluated, even if patients do not clinically appear volume overloaded. Antihypertensive drugs should be prescribed because of the persistently elevated ambulatory blood pressure. Dialysate sodium reduction should be considered, although the long term effects of this intervention are uncertain.

Extracellular Volume Overload and Increased Vasoconstriction in Patients With Recurrent Intradialytic Hypertension.

BACKGROUND/AIMS: Intradialytic hypertension (IH) occurs frequently in some hemodialysis patients and increases mortality risk. We simultaneously compared pre-dialysis, post-dialysis and changes in extracellular volume and hemodynamics in recurrent IH patients and controls. METHODS: We performed a case-control study among prevalent hemodialysis patients with recurrent IH and hypertensive hemodialysis controls. We used bioimpedance spectroscopy and impedance cardiography to compare pre-dialysis, post-dialysis, and intradialytic change in total body water (TBW) and extracellular water (ECW), as well as cardiac index (CI) and total peripheral resistance index (TPRI). RESULTS: The ECW/TBW was 0.453 (0.05) pre-dialysis and 0.427 (0.04) post-dialysis in controls vs. 0.478 (0.03) and 0.461 (0.03) in IH patients (p=0.01 post-dialysis). The ECW/TBW change was -0.027 (0.03) in controls and -0.013 (0.02) in IH patients (p=0.1). In controls, pre- and post-dialysis TPRI were 3254 (994) and 2469 (529) dynes/sec/cm2/m2 vs. 2983 (747) and 3408 (980) dynes/sec/cm2/m2 in IH patients (p=0.002 post-dialysis). There were between-group differences in TPRI change (0=0.0001), but not CI (p=0.09). CONCLUSIONS: Recurrent intradialytic hypertension is associated with higher post-dialysis extracellular volume and TPRI. Intradialytic TPRI surges account for the vasoconstrictive state post-dialysis, but intradialytic fluid shifts may contribute to post-hemodialysis volume expansion.

Evaluation and Treatment of Hypertension in End-Stage Renal Disease Patients on Hemodialysis.

Hypertension is one of the most common cardiovascular comorbidities in end-stage renal disease patients on hemodialysis. Its complex pathophysiology is related to extracellular volume overload, increased vascular resistance stemming from factors related to uremia or abnormal signaling from the failing kidneys, as well as the unique blood pressure changes that take place during and between hemodialysis treatments. Despite the changing nature of blood pressure over time in hemodialysis patients, hypertension diagnosed in or out of the hemodialysis unit is associated with increased cardiovascular morbidity and mortality. This review details the causes of hypertension in hemodialysis patients and provides an updated review of the clinical consequences and management of hypertension.