Electronic alerts and a care bundle for acute kidney injury-an Australian cohort study.

BACKGROUND: Early recognition of hospital-acquired acute kidney injury (AKI) may improve patient management and outcomes. METHODS: This multicentre study was conducted at three hospitals (H1-intervention; H2 and H3-controls) served by a single laboratory. The intervention bundle [an interruptive automated alerts (aAlerts) showing AKI stage and baseline creatinine in the eMR, a management guide and junior medical staff education] was implemented only at H1. Outcome variables included length-of-stay (LOS), all-cause in-hospital mortality and management quality. RESULTS: Over 6 months, 639 patients developed AKI (265 at H1 and 374 at controls), with 94.7% in general wards; 537 (84%) patients developed Stage 1, 58 (9%) Stage 2 and 43 (7%) Stage 3 AKI. Median LOS was 9 days (IQR 4-17) and was not different between intervention and controls. However, patients with AKI stage 1 had shorter LOS at H1 [median 8 versus 10 days (P = 0.021)]. Serum creatinine had risen prior to admission in most patients. Documentation of AKI was better in H1 (94.8% versus 83.4%; P = 0.001), with higher rates of nephrology consultation (25% versus 19%; P = 0.04) and cessation of nephrotoxins (25.3 versus 18.8%; P = 0.045). There was no difference in mortality between H1 versus controls (11.7% versus 13.0%; P = 0.71). CONCLUSIONS: Most hospitalized patients developed Stage 1 AKI and developed AKI in the community and remained outside the intensive care unit (ICU). The AKI eAlert bundle reduced LOS in most patients with AKI and increased AKI documentation, nephrology consultation rate and cessation of nephrotoxic medications.

The use of medium cutoff dialyzers in patients with multiple myeloma and acute kidney injury requiring hemodialysis: A systematic review.

BACKGROUND: Patients with multiple myeloma and high serum levels of circulating free light chains (FLC) have increased risk of acute kidney injury (AKI) secondary to cast nephropathy and is associated with poor survival. Despite removal of FLC by medium cutoff (MCO) dialyzer, the role of MCO hemodialysis (HD) in the treatment of cast nephropathy and its clinical benefits remain unknown. METHODS: A systematic review was conducted to establish the effectiveness of MCO dialyzer and clinical outcomes, compared to other forms of dialyzers in the removal of FLC, in myeloma patients with AKI. The primary outcome was effectiveness of MCO-HD in reducing serum FLC. The secondary outcomes were HD independence, estimated glomerular filtrate rate, mortality rates, length of hospitalization, rebound of serum FLC before the next dialysis, removal of other molecules during dialysis, and adverse events. RESULTS: We identified three case series, with a total of 17 patients. There were no randomized controlled trials (RCTs) or cohort studies. These case series showed that MCO dialyzer was effective in the removal of FLC and led to a reduction in FLC concentration post-dialysis. The majority of the case series did not have comparator arm and renal and/or other clinical outcomes. CONCLUSION: MCO dialyzer appeared to be effective in the removal of FLC based on the existing limited data. However, more data, particularly large-scale RCTs, are needed to assess the use of MCO dialyzer in reducing serum FLC and its effect on clinical outcomes in patients with multiple myeloma and AKI.

Regional citrate anticoagulation vs systemic heparin anticoagulation for double-filtration plasmapheresis.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) has been utilized for immunomodulation in kidney transplantation. Anticoagulation is important to maintain circuit patency during DFPP. We aimed to compare the efficacy and safety of regional citrate anticoagulation (RCA) with systemic heparin anticoagulation during DFPP in kidney transplant recipients. METHODS: A retrospective cohort study was conducted to compare the efficacy and safety of RCA (RCA-DFPP) to systemic heparin anticoagulation (Hep-DFPP) for DFPP among kidney transplant recipients in a single tertiary center. RESULTS: A total of 112 sessions of DFPP were performed for 23 subjects, of which 62 sessions were RCA-DFPP and 50 sessions were Hep-DFPP. There were 13 sessions (11.6%) of premature circuit clotting, 10 sessions (16.1%) for RCA-DFPP and 3 sessions (6.0%) for Hep-DFPP (P = .10). All premature circuit clotting episodes occurred in subjects who underwent DFPP through a vascular catheter. Premature circuit clotting was associated with the use of a vascular catheter (odds ratio [OR] 14.2, 95% confidence interval [CI] 2.7-73.7; P < .01) and high postfilter ionized calcium (OR 12.7, 95% CI 1.4-112.5; P < .01). There was no major bleeding event. Hep-DFPP was associated with higher occurrence of hypocalcemia (OR 1.1, 95% CI 1.0-1.2; P < .01) and metabolic acidosis (OR 1.4, 95% CI 1.2-2.0; P = .04), while hypomagnesemia was more common for RCA-DFPP (OR 2.9, 95% CI 1.1-7.4; P = .03). CONCLUSION: Amongst kidney transplant patients who receive DFPP therapy, RCA-DFPP may be comparable to Hep-DFPP for the maintenance of circuit patency. Functioning vascular access is vital in avoiding premature clotting of the circuit. Close monitoring of electrolyte imbalances and coagulopathy related to DFPP is recommended.

Regional Citrate Anticoagulation during Double-Filtration Plasmapheresis in Kidney Transplant Recipients: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) may be used for immunomodulation in kidney transplant (KTx). While DFPP reduces plasma product exposure, risk of circuit clotting merits adequate anticoagulation. Regional citrate anticoagulation (RCA) avoids the risks of systemic anticoagulation, but a protocol for RCA-DFPP is not previously widely described. METHODS: We conducted a single-center retrospective cohort study involving adult (≥21 years old) KTx recipients who underwent RCA-DFPP from 2018 to 2020 to investigate efficacy and safety for an RCA protocol during DFPP in KTx recipients. RESULTS: Fifty-one (85%) of 60 RCA-DFPP sessions in 17 patients completed without circuit clotting. Circuit clotting was associated with high post-filter ionized calcium (28 vs. 3.7%, odds ratio 10.1, 95% CI 1.1-89.4, p = 0.037). Hypo- and hypercalcemia developed in 5 (8.3%) and 8 (13.3%) sessions, respectively, but no adverse effects were noted despite severe hypocalcemia in one. There was no significant change in pre- and post-RCA-DFPP sodium, bicarbonate, albumin, and platelet levels. With regards DFPP procedure, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) was observed following 38 (64.4%) and 12 (20.3%) sessions, respectively. Severely prolonged (>1.5 × upper limit normal) PT and aPTT were recorded in 2 sessions each. Expectedly, hypofibrinogenemia developed after 31 (51.7%) sessions: including 4 (6.7%) severe hypofibrinogenemia (<0.5 g/L). Two patients developed bleeding requiring blood product transfusion. The median total volume of fluids administered per session was 1.495 (1.373-1.612) L; post-RCA-DFPP significant weight gain of 0.5 (0-1.25) kg was noted. Diuretic was commenced or dose increased following 20 (33.3%) sessions for fluid balance management. DISCUSSION/CONCLUSION: Protocol-based RCA for DFPP is feasible and safe in KTx recipients. However, DFPP-related coagulopathy can develop consequent to treatment; caution should be exercised for patients with bleeding risk. Close monitoring and management of the patients' electrolytes, especially hypocalcemia and hypomagnesemia, and fluid status is recommended.

Analysis of a fully infectious bio-orthogonally modified human virus reveals novel features of virus cell entry.

We report the analysis of a complex enveloped human virus, herpes simplex virus (HSV), assembled after in vivo incorporation of bio-orthogonal methionine analogues homopropargylglycine (HPG) or azidohomoalanine (AHA). We optimised protocols for the production of virions incorporating AHA (termed HSVAHA), identifying conditions which resulted in normal yields of HSV and normal particle/pfu ratios. Moreover we show that essentially every single HSVAHA capsid-containing particle was detectable at the individual particle level by chemical ligation of azide-linked fluorochromes to AHA-containing structural proteins. This was a completely specific chemical ligation, with no capsids assembled under normal methionine-containing conditions detected in parallel. We demonstrate by quantitative mass spectrometric analysis that HSVAHA virions exhibit no qualitative or quantitative differences in the repertoires of structural proteins compared to virions assembled under normal conditions. Individual proteins and AHA incorporation sites were identified in capsid, tegument and envelope compartments, including major essential structural proteins. Finally we reveal novel aspects of entry pathways using HSVAHA and chemical fluorochrome ligation that were not apparent from conventional immunofluorescence. Since ligation targets total AHA-containing protein and peptides, our results demonstrate the presence of abundant AHA-labelled products in cytoplasmic macrodomains and tubules which no longer contain intact particles detectable by immunofluorescence. Although these do not co-localise with lysosomal markers, we propose they may represent sites of proteolytic virion processing. Analysis of HSVAHA also enabled the discrimination from primary entering from secondary assembling virions, demonstrating assembly and second round infection within 6 hrs of initial infection and dual infections of primary and secondary virus in spatially restricted cytoplasmic areas of the same cell. Together with other demonstrated applications e.g., in genome biology, lipid and protein trafficking, this work further exemplifies the utility and potential of bio-orthogonal chemistry for studies in many aspects of virus-host interactions.

Description of parallel and sequential configurations for concurrent therapeutic plasma exchange and continuous kidney replacement therapy in adults.

Therapeutic plasma exchange (TPE) and continuous kidney replacement therapy (CKRT) are extracorporeal therapeutic procedures often implemented in management of patients. Critically ill patients may be afflicted with disease processes that require both TPE and CKRT. Performing TPE discontinuous with CKRT is technically easier, however, it disrupts CKRT and may compromise with CKRT efficiency or hemofilter life. Concurrent TPE with CKRT offers several advantages including simultaneous control of disease process and correction of electrolyte, fluid, and acid-base disturbances that may accompany TPE. Additionally, TPE may be performed by either centrifugation method or membrane plasma separation method. The technical specifications of these methods may influence the methodology of concurrent connections. This report describes and reviews two different approaches to circuit arrangements when establishing concurrent TPE and CKRT.

Augmented Adsorptive Blood Purification during Continuous Veno-Venous Haemodiafiltration in a Severe Septic, Acute Kidney Injury Patient: Use of oXiris®: A Single Centre Case Report.

The use of the oXiris® haemofilter during continuous veno-venous haemodiafiltration (CVVHDF) for acute kidney injury (AKI) and severe sepsis is not completely understood. Although this filter has in vitro adsorptive properties for blood-borne cytokines and other humoural mediators of sepsis, its clinical usefulness is uncertain. Given its inherent adsorptive limitation for septic mediators, we developed a CVVHDF protocol in which the oXiris haemofilter was electively changed every 12 h even though there was no clotting or adverse circuit pressures. Augmented filter membrane adsorption was conducted for 3 consecutive days. We treated a critically ill patient with severe sepsis secondary to a gram-negative bacterial infection and sepsis-associated acute kidney injury (SA- AKI) in this way. The patient required high-dose vasopressor support, required mechanical ventilation, had received 12 h of CVVHDF with conventional M100 haemofilter, was on broad spectrum antibiotics and other conventional intensive care unit (ICU) care, prior to institution of the frequent oXiris haemofilter change protocol. Following the start of elective 12 hourly oXiris filter change, the patient showed reduction in the need for vasopressor and by Day 4 of this SA- AKI frequent filter change protocol, vasopressor requirement ceased, he was extubated. He survived ICU and but not hospital stay. To this end, more clinical studies are needed.

A prospective study of clinical characteristics and outcomes of acute kidney injury in a tertiary care Centre.

BACKGROUND: Acute kidney injury (AKI) is a major global health problem. We aim to evaluate the epidemiology, risk factors and outcomes of AKI episodes in our single centre. METHODOLOGY: We prospectively identified 422 AKI and acute on chronic kidney disease episodes in 404 patients meeting KDIGO definitions using electronic medical records and clinical data from 15th July to 22nd October 2016, excluding patients with baseline estimated GFR (eGFR) of < 15 mL/min. Patients were followed up till 6 months after AKI diagnosis. RESULTS: The mean age was 65.8 ± 14.1. Majority of patients were male (58.2%) of Chinese ethnicity (68.8%). One hundred and thirty-two patients (32.6%) were diagnosed in acute care units. Seventy-five percent of patients developed AKI during admission in a non-Renal specialty. Mean baseline eGFR was 50.2 ± 27.7 mL/min. Mean creatinine at AKI diagnosis was 297 ± 161 µmol/L. Renal consultations were initiated at KDIGO Stages 1, 2 and 3 in 58.9, 24.5 and 16.6% of patients, respectively. Three hundred and ten (76.7%) patients had a single etiology of AKI with the 3 most common etiologies of AKI being pre-renal (27.7%), sepsis-associated (25.5%) and ischemic acute tubular necrosis (15.3%). One hundred and nine (27%) patients received acute renal replacement therapy. In-hospital mortality was 20.3%. Six-month mortality post-AKI event was 9.4%. On survival analysis, patients with KDIGO Stage 3 AKI had significantly shorter survival than other stages. CONCLUSION: AKI is associated with significant in-hospital to 6-month mortality. This signifies the pressing need for AKI prevention, early detection and intervention in mitigating reversible risk factors in order to optimize clinical outcomes.

Impact of simulation-based learning on immediate outcomes of temporary haemodialysis catheter placements by nephrology fellows.

AIM: Traditional apprenticeship model (AM) of teaching in invasive procedures such as temporary haemodialysis catheter (THDC) insertion can result in propagation of errors and complications. Simulation-based learning (SBL) offers standardization of skills and allows trainees to repeatedly practice invasive procedures prior to performing them on actual patient. METHODS: Retrospective cohort study of first-, second- and third-year Nephrology Fellows from a tertiary teaching hospital from September 2008 to September 2015. The intervention group (n = 9) received simulation training in ultrasound-guided THDC placement. The historical control group (n = 12) received training through traditional AM. The primary and secondary outcomes were the immediate complications and success rates of THDC insertion. RESULTS: A total of 2481 THDCs were placed in 1787 patients. Success rate of internal jugular THDC placement for AM vs. SBL Fellow was 99.8% versus 100% (P = 0.90), while the success rate for femoral THDC placement was 99.6% versus 99.2% (P = 0.53). SBL Fellows reported fewer overall peri-procedure complications (8.3% vs. 11.2%, P = 0.02) and mechanical complications (1% vs. 2.4%, P = 0.02) compared to AM Fellows. The rate of reported technical difficulty was similar (7.5% vs. 9.2%, P = 0.17). After adjusting for side and site of THDC placement, body mass index and laboratory indices, THDC inserted by AM Fellows were independently associated with increased overall peri-procedure complications (OR = 1.396, 95% CI: 1.052-1.854, P = 0.02) and mechanical complications (OR = 2.481, 95% CI: 1.178-4.810, P = 0.02). CONCLUSIONS: Simulation-based learning was associated with lower procedure related complications and should be an integral component in the teaching of procedural skills in Nephrology.

Severe gastrointestinal cytomegalovirus disease in two patients with renal vasculitis after immunosuppression.

Although the use of current immunosuppressive regimens has significantly improved the outcomes of autoimmune renal diseases, infectious complications remain an important clinical concern. Cytomegalovirus (CMV) infection has been shown to be one of the major causes of mortality in this group of patients. We report two cases of renal vasculitis (Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)) that developed into severe gastrointestinal CMV disease and manifested with massive small bowel bleeding, resulting in an eventual fatal outcome for one of the patients. Risk factors, pathogenesis, role of immunosuppression in the development of CMV infection, and antiviral treatment are discussed in this review. These cases highlight the need for further research to evaluate the complex mechanisms between immunosuppression and CMV occurrence as well as the role of antiviral prophylaxis in high-risk patients undergoing immunosuppressive therapies.
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Non-steroidal anti-inflammatory drugs in chronic kidney disease and risk of acute adverse kidney events according to route of administration.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs (NSAIDs) have lower risks for cardiovascular disease and gastrointestinal adverse effects compared to oral NSAIDs, but there are little data regarding their kidney risks in chronic kidney disease (CKD). We evaluated the risk of adverse acute kidney outcomes in CKD according to route of NSAID administration. METHODS: Retrospective cohort study of adults with CKD (eGFR less than 60 ml/min/1.73 m2) who received prescriptions between 2015 and 2017 from a major healthcare cluster in Singapore. The adverse acute kidney outcomes were acute kidney injury (AKI) and need for nephrology specialist consult within 30 days. RESULTS: Among 6298 adults with CKD (mean age 72.1 ± 13.3 years and eGFR 41.9 ± 12.2 ml/min/1.73 m2), systemic and topical NSAIDs were prescribed in 16.7% and 32.0%, respectively. Incident AKI (any severity), KDIGO Stage 2 or 3 AKI, and need for nephrology specialist consult occurred in 16.7%, 2.6%, and 10.6% of the study cohort, respectively. After adjusting for age, diabetes, recent cardiovascular hospitalization, baseline eGFR, RAAS blocker and diuretic, systemic NSAIDs, and topical NSAIDs, compared with the no-NSAID group, were independently associated with incident AKI [adjusted OR 1.77 (95% CI 1.46-2.15) and 1.38 (1.18-1.63), respectively]. Moderate and severe AKI (adjusted OR 1.68, 95% CI 1.09-2.58, p = 0.02) and need for nephrology consults (adjusted OR 1.41, 95% CI 1.09-1.82, p = 0.008) were also increased in systemic NSAIDs. CONCLUSION: Among adults with CKD, both systemic and topical NSAIDs were independently associated with acute adverse kidney outcomes.

Development and validation of an interpretable clinical score for early identification of acute kidney injury at the emergency department.

Acute kidney injury (AKI) in hospitalised patients is a common syndrome associated with poorer patient outcomes. Clinical risk scores can be used for the early identification of patients at risk of AKI. We conducted a retrospective study using electronic health records of Singapore General Hospital emergency department patients who were admitted from 2008 to 2016. The primary outcome was inpatient AKI of any stage within 7 days of admission based on the Kidney Disease Improving Global Outcome (KDIGO) 2012 guidelines. A machine learning-based framework AutoScore was used to generate clinical scores from the study sample which was randomly divided into training, validation and testing cohorts. Model performance was evaluated using area under the curve (AUC). Among the 119,468 admissions, 10,693 (9.0%) developed AKI. 8491 were stage 1 (79.4%), 906 stage 2 (8.5%) and 1296 stage 3 (12.1%). The AKI Risk Score (AKI-RiSc) was a summation of the integer scores of 6 variables: serum creatinine, serum bicarbonate, pulse, systolic blood pressure, diastolic blood pressure, and age. AUC of AKI-RiSc was 0.730 (95% CI 0.714-0.747), outperforming an existing AKI Prediction Score model which achieved AUC of 0.665 (95% CI 0.646-0.679) on the testing cohort. At a cut-off of 4 points, AKI-RiSc had a sensitivity of 82.6% and specificity of 46.7%. AKI-RiSc is a simple clinical score that can be easily implemented on the ground for early identification of AKI and potentially be applied in international settings.

Non-Steroidal Anti-Inflammatory Drugs and Risk of Acute Kidney Injury and Hyperkalemia in Older Adults: A Retrospective Cohort Study and External Validation of a Clinical Risk Model.

AIM: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used analgesics among older adults. Adverse effects may be avoided by careful patient selection. We aimed to evaluate the incidence of acute kidney injury (AKI) and/or hyperkalemia, risk factors, and the accuracy of an NSAID risk prediction model in a cohort of Asian older adults. METHODS: We conducted a retrospective cohort study of older adults, age 65 years and above, who received prescriptions between March 2015 and December 2017 from Singapore's largest cluster of public healthcare institutions. Factors associated with 30-day incident acute kidney injury and/or hyperkalemia were evaluated with multivariable regression analysis. Calibration and discrimination of the Nash prediction model were assessed using the Hosmer-Lemeshow goodness-of-fit test and C-statistic, respectively. RESULTS: The primary outcome occurred in 16.7% of 12,798 older adults. Topical NSAIDs (adjusted OR 1.29, 95% CI 1.15-1.45), systemic NSAIDs of 1-14 days' duration (adjusted OR 1.43, 95% CI 1.27-1.62), and systemic NSAIDs > 14 days (adjusted OR 1.84, 95% CI 1.37-2.49) were independently associated with the primary outcome, compared with no NSAID. Diabetes mellitus, cardiovascular disease, lower estimated glomerular filtration rate (eGFR), and diuretics were also independently associated with increased incident AKI and/or hyperkalemia. When applied to older adults with systemic NSAIDs > 14 days (n = 305), the Nash risk model had poor calibration (p < 0.001) and poor discrimination with C-statistic 0.527 (0.438, 0.616). CONCLUSIONS: Longer NSAID duration and systemic compared with topical route were associated with incremental odds for acute renal events. Further studies are required to improve the available risk model to guide NSAID prescriptions in older adults.

Effectiveness and acceptability of a multidisciplinary approach in improving the care of patients with advanced chronic kidney disease: a pilot study.

OBJECTIVE: This study aimed at determining the feasibility of conducting a large-scale pragmatic effectiveness study on the implementation of multidisciplinary care (MDC) program for patients with advanced chronic kidney disease (CKD). METHODS: This is a single-arm pre-post intervention design pilot study over 12 months. Participants with an estimated glomerular filtration rate (eGFR) between 11 and 20 ml/min/1.73m2 were screened and recruited at the initial MDC clinic visit and followed for 12 months. Clinical parameters, KDQOL™-36, questionnaires, and interviews were collected, administered, and analysed for enrolment and completion rates, baseline characteristics, implementation fidelity, adherence to CKD interventions, eGFR decline, CKD complications, health-related quality of life, and participants' acceptability of the program. RESULTS: The study enrolment and completion rates were 43.1% (50/116 screened) and 66.0% (33/50 recruited) respectively. The participants had a mean age of 68.5 years (SD9.0) and a mean eGFR of 15.4 ml/min/1.73m2(3.2). After 12 months of MDC program, there was increased adherence to CKD interventions (difference  - 0.6(1.0), 95%CI  - 1.1,  - 0.1, p = 0.02). There was good participants' acceptability of the program with participants being more satisfied with the waiting time and having a better understanding of kidney failure after attending the program. No difference in the eGFR decline noted (difference 0.0 ml/min/1.73m2(5.3), 95%CI  - 1.9, 1.9, p = 1.00). CONCLUSION: Our pilot data suggest increased adherence to CKD interventions and good acceptability to MDC program, albeit no difference in eGFR decline probably because of the small sample size. However, reasons for overall low enrolment and completion rates need to be explored and addressed while designing a future large-scale randomised controlled trial.

The details are in the genome-wide SNPs: Fine scale evolution of the Malaysian weedy rice.

Weedy rice (Oryza spp.) is a major nuisance to rice farmers from all over the world. Although the emergence of weedy rice in East Malaysia on the island of Borneo is very recent, the threat to rice yield has reached an alarming stage. Using 47,027 genotyping-by-sequencing (GBS)-derived SNPs and candidate gene analysis of the plant architecture domestication gene TAC1, we assessed the genetic variations and evolutionary origin of weedy rice in East Malaysia. Our findings revealed two major evolutionary paths for genetically distinct weedy rice types. Whilst the cultivar-like weedy rice are very likely to be the weedy descendant of local coexisting cultivars, the wild-like weedy rice appeared to have arisen through two possible routes: (i) accidental introduction from Peninsular Malaysia weedy rice populations, and (ii) weedy descendants of coexisting cultivars. The outcome of our genetic analyses supports the notion that Sabah cultivars and Peninsular Malaysia weedy rice are the potential progenitors of Sabah weedy rice. Similar TAC1 haplotypes were shared between Malaysian cultivated and weedy rice populations, which further supported the findings of our GBS-SNP analyses. These different strains of weedy rice have convergently evolved shared traits, such as seeds shattering and open tillers. A comparison with our previous simple-sequence repeat-based population genetic analyses highlights the strength of genome-wide SNPs, including detection of admixtures and low-level introgression events. These findings could inform better strategic management for controlling the spread of weedy rice in the region.

Contribution of Fc-dependent cell-mediated activity of a vestigial esterase-targeting antibody against H5N6 virus infection.

The highly pathogenic avian influenza A (H5N6) virus has caused sporadic human infections with a high case fatality rate. Due to the continuous evolution of this virus subtype and its ability to transmit to humans, there is an urgent need to develop effective antiviral therapeutics. In this study, a murine monoclonal antibody 9F4 was shown to display broad binding affinity against H5Nx viruses. Furthermore, 9F4 can neutralize H5N6 pseudotyped particles and prevent entry into host cells. Additionally, ADCC/ADCP deficient L234A, L235A (LALA) and CDC deficient K322A mutants were generated and displayed comparable binding affinity and neutralizing activity as wild type 9F4 (9F4-WT). Notably, 9F4-WT, 9F4-LALA and 9F4-K322A exhibit in vivo protective efficacies against H5N6 infections in that they were able to reduce viral loads in mice. However, only 9F4-WT and 9F4-K322A but not 9F4-LALA were able to reduce viral pathogenesis in H5N6 challenged mice. Furthermore, depletion of phagocytic cells in mice lungs nullifies 9F4-WT's protection against H5N6 infections, suggesting a crucial role of the host's immune cells in 9F4 antiviral activity. Collectively, these findings reveal the importance of ADCC/ADCP function for 9F4-WT protection against HPAIV H5N6 and demonstrate the potential of 9F4 to confer protection against the reassortant H5-subtype HPAIVs.

Renal outcomes of intensive care burn patients in an Asian tertiary centre.

INTRODUCTION: Acute kidney injury (AKI) is a frequent complication of severe burn injury and is associated with a high mortality rate of up to 80%. We aimed to establish the incidence, mortality rate, and factors related to mortality in adult patients with severe burn injury and AKI with renal replacement therapy (RRT) in Singapore. METHODS: We performed a retrospective cohort study of severely burned patients who were admitted to the Burns Intensive Care Unit (BICU) at the Singapore General Hospital (SGH) from January 2008 to December 2016. We compared patients with AKI with RRT who survived with those who did not survive. As there were changes in the protocol for burns management after 2013, we also compared patients with AKI with RRT who survived with non-survivors in each of the 2008-2012 and 2013-2016 cohorts. RESULTS: Data of 201 patients were studied. The incidence of AKI with RRT use in severe burn injury was 21.9% and their mortality rate was 50.0%. The non-survivors had significantly higher median burned total body surface area (p = 0.043), earlier AKI (p = 0.046), earlier use of RRT (p = 0.035), lower rate of renal recovery (p = <0.0001), higher rates of adult respiratory distress syndrome (ARDS) (p = 0.005) and shock with vasopressors (p = 0.009) compared to the survivors. The survival rate was 36.8% in the 2008-2012 cohort, but improved to 60.0% in the 2013-2016 cohort. In the 2008-2012 cohort, the non-survivors developed AKI earlier (day 0 admission vs. day 3 admission, p = 0.039), and were initiated on RRT at lower serum creatinine level (173.5 µmol/L vs. 254.0 µmol/L, p = 0.042), when compared to the survivors in this same cohort. On the other hand, there were no significant differences in the renal status and fluid balance parameters between the non-survivors and survivors in the 2013-2016 cohort. CONCLUSIONS: The incidence of AKI with RRT in the Singapore study cohort was high, but their mortality rate was relatively lower compared to other study cohorts. Severity of AKI and use of RRT were associated with poor prognosis. Large scale study is required to further study the risk factors for mortality in this group of patients and establish cause-and-effect relationship.

Healthcare professionals' perceptions of the role of a multidisciplinary approach in improving the care of patients with advanced chronic kidney disease.

OBJECTIVE: To explore and understand the experiences of healthcare professionals (HCPs) delivering care in a multidisciplinary care (MDC) clinic for advanced chronic kidney disease (CKD) patients. METHODS: This is a qualitative study based on semi-quantitative questionnaire and semi-structured interviews with thematic analysis and deductive mapping onto the Theoretical Framework of Acceptability. Sixteen HCPs caring for advanced CKD patients in a MDC clinic in a tertiary teaching hospital in Singapore were recruited based on maximum variation sampling procedures. RESULTS: The majority of the HCPs were supportive of a MDC clinic. There was a positive overall opinion of the programme [median 7.0 of 10.0 (IQR 7.0-8.0)], high satisfaction ratings for interaction with other members of team [6.9 (5.3-8.0)] and time spent with patients [7.0 (5.3-7.0)]. Thematic analysis of the interviews identified the value of MDC clinic in the provision of one-stop care, the improvement in communication and collaboration between HCPs, the facilitation of patient activation to make planned kidney care decisions, and the optimisation of medications. The main challenges were lack of continuity of care, manpower constraints, poor patient navigation between HCPs, poor patient attendance with allied HCPs, and the perception of increased cost and time spent by patients in each MDC clinic visit. The proposed interventions were notification of patients beforehand of the MDC clinic schedule and provision of navigation to patients within the MDC clinic. CONCLUSION: A multidisciplinary care clinic for advanced chronic kidney disease patients was viewed positively by the majority of the healthcare professionals, with areas for improvement.

A NS1-binding monoclonal antibody interacts with two residues that are highly conserved in seasonal as well as newly emerged influenza A virus.

The non-structural protein 1 (NS1) of influenza A virus (IAV) is a multifunctional protein that antagonizes host antiviral responses, modulating virus pathogenesis. As such, it serves as a good target for research and diagnostic assay development. In this study, we have generated a novel monoclonal antibody (mAb) 19H9 and epitope mapping revealed that two residues, P85 and Y89, of NS1 are essential for interacting with this mAb. Furthermore, residues P85 and Y89 are found to be highly conserved across different IAV subtypes, namely seasonal H1N1 and H3N2, as well as the highly pathogenic H5N1 and H5N6 avian strains. Indeed, mAb 19H9 exhibits broad cross-reactivity with IAV strains of different subtypes. The binding of mAb 19H9 to residue Y89 was further confirmed by the abrogation of interaction between NS1 and p85ß. Additionally, mAb 19H9 also detected NS1 proteins expressed in IAV-infected cells, showing NS1 intracellular localization in the cytoplasm and nucleolus. To our knowledge, mAb 19H9 is the first murine mAb to bind at the juxtaposition between the N-terminal RNA-binding domain and C-terminal effector domain of NS1. It could serve as a useful research tool for studying the conformational plasticity and dynamic changes in NS1.