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Fulltext Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update

Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, et al.

Hepatol Int, 2019 Jul;13(4):353-390.
PMID: 31172417 DOI: 10.1007/s12072-019-09946-3

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.

Matched MeSH terms: Sepsis/etiology
Fulltext 4'-O-substitutions determine selectivity of aminoglycoside antibiotics

Perez-Fernandez D, Shcherbakov D, Matt T, Leong NC, Kudyba I, Duscha S, et al.

Nat Commun, 2014;5:3112.
PMID: 24473108 DOI: 10.1038/ncomms4112

Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets.

Matched MeSH terms: Sepsis/drug therapy
Fulltext Subcutaneous panniculitic T-cell lymphoma-review of five cases

Ng TG, Ayadurai K, Gangaram HB, Hussein SH

Med J Malaysia, 2006 Dec;61(5):586-91.
PMID: 17623960 MyJurnal

Subcutaneous panniculitic T-cell lymphoma (SPTL) is a rare variant of cutaneous T-cell lymphoma where lymphoma cells infiltrate preferentially into subcutaneous tissue. Five cases of SPTL were seen during the period from 2001-2004 at the Department of Dermatology, Hospital Kuala Lumpur. All five presented with multiple subcutaneous nodules on the face, trunk and limbs of one week to six months duration with associated fever and loss of weight. Physical examination showed multiple tender, erythematous indurated plaques and subcutaneous nodules on their face, trunk and limbs. One patient also presented with unhealing ulcerated nodules. Two patients had hepatosplenomegaly and one hepatomegaly. Two patients had pancytopaenia while the other three had leucopaenia. One patient had deranged liver function. Out of the five patients, three had bone marrow examination with haemophaegocytosis in two and one hypocellular marrow. Skin biopsy of all patients showed infiltration with atypical lymphoid cells in the upper dermis and subcutaneous fat. These neoplastic cells showed positivity for CD3 and CD30 in three patients with CD8, TIA-1 and LCA (Leucocyte common antigen) being positive in one patient. One patient treated with prednisolone and subcutaneous Roferon 3Mu three times a week since 2001 was in remission. Two patients who were planned for chemotherapy had deteriorated rapidly and succumbed to septicaemia from pancytopaenia. Subcutaneous panniculitic T-cell lymphoma has been reported to show two distinct clinical presentations. The first is characterized by an indolent course with good prognosis and the second with rapid clinical deterioration, haemophaegocytosis and death. Both presentations were seen in our five patients seem to demonstrate these two subtypes of SPTL.

Matched MeSH terms: Sepsis
The mycological and molecular study of Hortaea werneckii isolated from blood and splenic abscess

Ng KP, Soo-Hoo TS, Na SL, Tay ST, Hamimah H, Lim PC, et al.

Mycopathologia, 2005 Jun;159(4):495-500.
PMID: 15983734

Hortaea werneckii is an environmental dematiaceous fungus found in the halophilic environment. It causes tinea nigra. We report the isolation of H. werneckii from blood and splenic abscess of two patients with acute myelomonocytic leukaemia. H. werneckii grew at room temperature but not at 37 degrees C, it was identified by biochemical tests, growth characteristics and the presence of conspicuous collarette intercalary on dividing yeast cells. The use of specific oligonucleotide primer Hor-F (5'-TGGACACCTTCA TAACTCTTG-3') and Hor-R (5'-TCACAACGCTTAGAGACGG-3') confirmed the two isolates were H. werneckii. The sequence for 281 nucleotide of HW299 and HW403 were 99% identical but differed only in one nucleotide. In vitro anti-fungal susceptibility testing showed that the isolates were resistant to amphotericin B and flucytosine.

Matched MeSH terms: Sepsis
Six-year multicenter study on short-term peripheral venous catheters-related bloodstream infection rates in 727 intensive care units of 268 hospitals in 141 cities of 42 countries of Africa, the Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific Regions: International Nosocomial Infection Control Consortium (INICC) findings

Rosenthal VD, Bat-Erdene I, Gupta D, Belkebir S, Rajhans P, Zand F, et al.

Infect Control Hosp Epidemiol, 2020 05;41(5):553-563.
PMID: 32183925 DOI: 10.1017/ice.2020.20

BACKGROUND: Short-term peripheral venous catheter-related bloodstream infection (PVCR-BSI) rates have not been systematically studied in resource-limited countries, and data on their incidence by number of device days are not available.
METHODS: Prospective, surveillance study on PVCR-BSI conducted from September 1, 2013, to May 31, 2019, in 727 intensive care units (ICUs), by members of the International Nosocomial Infection Control Consortium (INICC), from 268 hospitals in 141 cities of 42 countries of Africa, the Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific regions. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System.
RESULTS: We followed 149,609 ICU patients for 731,135 bed days and 743,508 short-term peripheral venous catheter (PVC) days. We identified 1,789 PVCR-BSIs for an overall rate of 2.41 per 1,000 PVC days. Mortality in patients with PVC but without PVCR-BSI was 6.67%, and mortality was 18% in patients with PVC and PVCR-BSI. The length of stay of patients with PVC but without PVCR-BSI was 4.83 days, and the length of stay was 9.85 days in patients with PVC and PVCR-BSI. Among these infections, the microorganism profile showed 58% gram-negative bacteria: Escherichia coli (16%), Klebsiella spp (11%), Pseudomonas aeruginosa (6%), Enterobacter spp (4%), and others (20%) including Serratia marcescens. Staphylococcus aureus were the predominant gram-positive bacteria (12%).
CONCLUSIONS: PVCR-BSI rates in INICC ICUs were much higher than rates published from industrialized countries. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs in resource-limited countries.

Matched MeSH terms: Sepsis
Fulltext Vaccine Efficacy of a Newly Developed Feed-Based Whole-Cell Polyvalent Vaccine against Vibriosis, Streptococcosis and Motile Aeromonad Septicemia in Asian Seabass, Lates calcarifer

Mohamad A, Zamri-Saad M, Amal MNA, Al-Saari N, Monir MS, Chin YK, et al.

Vaccines (Basel), 2021 Apr 10;9(4).
PMID: 33920311 DOI: 10.3390/vaccines9040368

Multiple infections of several bacterial species are often observed under natural farm conditions. The infections would cause a much more significant loss compared to a single infectious agent. Vaccination is an essential strategy to prevent diseases in aquaculture, and oral vaccination has been proposed as a promising technique since it requires no handling of the fish and is easy to perform. This research attempts to develop and evaluate a potential feed-based polyvalent vaccine that can be used to treat multiple infections by Vibrios spp., Streptococcus agalactiae, and Aeromonas hydrophila, simultaneously. The oral polyvalent vaccine was prepared by mixing formalin-killed vaccine of V. harveyi, S. agalactiae, and A. hydrophila strains with commercial feed pellet, and palm oil as an adjuvant was added to improve their antigenicity. Thereafter, a vaccinated feed pellet was tested for feed quality analysis in terms of feed stability in water, proximate nutrient analysis, and palatability, safety, and growth performance using Asian seabass, Lates calcarifer as a fish host model. For immune response analysis, a total of 300 Asian seabass juveniles (15.8 ± 2.6 g) were divided into two groups in triplicate. Fish of group 1 were not vaccinated, while group 2 was vaccinated with the feed-based polyvalent vaccine. Vaccinations were carried out on days 0 and 14 with oral administration of the feed containing the bacterin at 5% body weight. Samples of serum for antibody and lysozyme study and the spleen and gut for gene expression analysis were collected at 7-day intervals for 6 weeks. Its efficacy in protecting fish was evaluated in aquarium challenge. Following vaccination by the polyvalent feed-based vaccine, IgM antibody levels showed a significant (p < 0.05) increase in serum against Vibrio harveyi, Aeromonas hydrophila, and Streptococcus agalactiae and reached the peak at week 3, 5, and 6, respectively. The high-stimulated antibody in the serum remained significantly higher than the control (p < 0.05) at the end of the 6 weeks vaccination trial. Not only that, but the serum lysozyme level was also increased significantly at week 4 (p < 0.05) as compared to the control treatment. The immune-related gene, dendritic cells, C3, Chemokine ligand 4 (CCL4), and major histocompatibility complex class I (MHC I) showed significantly higher expression (p < 0.05) after the fish were vaccinated with the oral vaccine. In the aquarium challenge, the vaccine provided a relative percentage survival of 75 ± 7.1%, 80 ± 0.0%, and 80 ± 0.0% after challenge with V. harveyi, A. hydrophila, and S. agalactiae, respectively. Combining our results demonstrate that the feed-based polyvalent vaccine could elicit significant innate and adaptive immunological responses, and this offers an opportunity for a comprehensive immunization against vibriosis, streptococcosis, and motile aeromonad septicemia in Asian seabass, Lates calcarifer. Nevertheless, this newly developed feed-based polyvalent vaccination can be a promising technique for effective and large-scale fish immunization in the aquaculture industry shortly.

Matched MeSH terms: Sepsis
An overview of Acinetobacter baumannii pathogenesis: Motility, adherence and biofilm formation

Mea HJ, Yong PVC, Wong EH

Microbiol Res, 2021 Jun;247:126722.
PMID: 33618061 DOI: 10.1016/j.micres.2021.126722

The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in critically ill patients. Its global spread, multi-drug resistance features and plethora of virulence factors make it a serious threat to public health worldwide. Though much effort has been expended in uncovering its successes, it continues to confound researchers due to its highly adaptive nature, mutating to meet the needs of a given environment. Its persistence in the clinical setting allows it to be in close proximity to a potential host, where contact can be made facilitating infection and colonization. In this article, we aim to provide a current overview of the bacterial virulence factors, specifically focusing on factors involved in the initial stages of infection, highlighting the role of adaptation facilitated by two-component systems and biofilm formation. Finally, the study of host-pathogen interactions using available animal models, their suitability, notable findings and some perspectives moving forward are also discussed.

Matched MeSH terms: Sepsis
Economic Impact of Pneumococcal Protein-D Conjugate Vaccine (PHiD-CV) on the Malaysian National Immunization Programme

Aljunid S, Maimaiti N, Ahmed Z, Muhammad Nur A, Md Isa Z, Azmi S, et al.

Value Health Reg Issues, 2014 May;3:146-155.
PMID: 29702920 DOI: 10.1016/j.vhri.2014.04.008

OBJECTIVE: To assess the cost-effectiveness of introducing pneumococcal polysaccharide and nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in the National Immunization Programme of Malaysia. This study compared introducing PHiD-CV (10 valent vaccine) with current no vaccination, as well as against the alternative 13-valent pneumococcal conjugate vaccine (PCV13).

METHODS: A lifetime Markov cohort model was adapted using national estimates of disease burden, outcomes of pneumococcal disease, and treatment costs of disease manifestations including pneumonia, acute otitis media, septicemia, and meningitis for a hypothetical birth cohort of 550,000 infants. Clinical information was obtained by review of medical records from four public hospitals in Malaysia from the year 2008 to 2009. Inpatient cost from the four study hospitals was obtained from a diagnostic-related group-based costing system. Outpatient cost was estimated using clinical pathways developed by an expert panel. The perspective assessed was that of the Ministry of Health, Malaysia.

RESULTS: The estimated disease incidence was 1.2, 3.7, 70, and 6.9 per 100,000 population for meningitis, bacteremia, pneumonia, and acute otitis media, respectively. The Markov model predicted medical costs of Malaysian ringgit (RM) 4.86 billion (US $1.51 billion) in the absence of vaccination. Vaccination with PHiD-CV would be highly cost-effective against no vaccination at RM30,290 (US $7,407) per quality-adjusted life-year gained. On comparing PHiD-CV with PCV13, it was found that PHiD-CV dominates PCV13, with 179 quality-adjusted life-years gained while saving RM35 million (US $10.87 million).

CONCLUSIONS: It is cost-effective to incorporate pneumococcal vaccination in the National Immunization Programme of Malaysia. Our model suggests that PHiD-CV would be more cost saving than PCV13 from the perspective of the Ministry of Health of Malaysia.

Study site: UKM Medical Centre, Hospital Kuala Lumpur, Hospital
Alor Setar, and Hospital Queen Elizabeth, Kota Kinabalu

Matched MeSH terms: Sepsis
A Single Institution's Experience with Cytogenetic and MRD Outcomes in Pediatric Acute Lymphoblastic Leukemia

Amjad A, Wali RM, Anjum S, Mansoor R

J Coll Physicians Surg Pak, 2019 Jun;29(6):549-552.
PMID: 31133155 DOI: 10.29271/jcpsp.2019.06.549

OBJECTIVE: To determine the frequency of cytogenetic type and its significance in the prognostic outcome of the pediatric patients in acute lymphoblastic leukemia (ALL), aged 1 to 15 years, and also determine the importance of minimal residual disease (MRD) in the management of the condition.
STUDY DESIGN: An observational study.
PLACE AND DURATION OF STUDY: Pediatric Oncology Ward, Shaukat Khanum Cancer Hospital, Lahore, from January 2015 to July 2017.
METHODOLOGY: Patients aged 1-15 years, diagnosed with ALL, were included. Studied variables were cytogenetic type and MRD outcome in patients with ALL. Patients under one year of age and more than 15 years, or those having comorbidities, were excluded.
RESULTS: Total 150 patients' data were retrieved from the Hospital database. One hundred and thirty-three belonged to age 1 to 5 years group (89%) and 17 (11%) were in 5 to 10 years group. The mean age of the patient was 4.3 +3.1 years. One hundred and two (68%) were males; whereas, 48 (32%) were females. Pre B acute lymphoblastic leukemia was diagnosed in 139 (93%) patients and 11(7%) were diagnosed with Pre T acute lymphoblastic leukemia. Standard risk was observed in 120 (80%) patients and 30 (20%) patients were on high risk as per National Cancer Institute (NCI) Guidelines. Regimen A was used in 125 (83.3%), Regimen B in 16 (10.7%), and Regimen C in 9 (6%) patients. BCR-ABL was positive in 2 (1.30%), TEL-AML in 68 (45%), MLL in 5 (3.30%), and normal in 54 (36%). MRD at day 29 was negative in 40 (93%) and positive in 3 (7%). The karyotyping was done in 128 (85%) patients, out of which 68 (53%) were hyperploids, 41 (32%) euploid, and 19 (15%) were hypoploid. Death was observed in 22 (15%) patients. Nineteen (86%) deaths were due to fungal and bacterial sepsis; and disease-related deaths were noted in 3 (14%) patients.
CONCLUSION: The role of MRD and cytogenetics in risk assessment has improved in the early prognosis determination.

Matched MeSH terms: Sepsis
Fulltext Frequent nasopharyngeal suctioning as a risk factor associated with neonatal coagulase-negative staphylococcal colonisation and sepsis

Boo NY, Suhaida AR, Rohana J

Singapore Med J, 2015 Mar;56(3):164-8.
PMID: 25532513

This case-control study aimed to determine whether catheter use was significantly associated with coagulase-negative staphylococci (CoNS) colonisation and/or sepsis in neonates.

Matched MeSH terms: Sepsis
Fulltext Deep vein thrombosis as a rare presentation in a female with anti-neutrophil cytoplasmic antibodies-associated vasculitis

Wan Ghazali WS, Mohammad N, Ismail AM

Arch Rheumatol, 2017 Jun;32(2):171-174.
PMID: 30375559 DOI: 10.5606/ArchRheumatol.2017.6108

This article aims to report a case of a young female patient with anti-neutrophil cytoplasmic antibodies-associated vasculitis complicated with pulmonary renal syndrome, multiple relapses, and who later developed venous thromboembolism. Pulmonary renal syndrome is a well- recognized and lethal complication; however, incidence of venous thromboembolism has not been well-described. In this article, we described a 38-year-old Malay female patient admitted in 2008 with three-month history of peripheral neuropathy of lower limbs and right ankle ulcers. Initial inflammatory markers were high and perinuclear Anti-Neutrophil Cytoplasmic Antibodies were positive. She was diagnosed as anti-neutrophil cytoplasmic antibodies-associated vasculitis and started on intravenous methylprednisolone with methotrexate. She presented with relapse of skin vasculitis complicated with pulmonary renal syndrome after being stable for one year. She was intubated and proceeded with plasmapheresis and hemodialysis. She completed six cycles of cyclophosphamide. Renal biopsy revealed chronic changes consistent with end stage renal disease. She further relapsed in 2011 with nasal blockage, epistaxis, and nasal deviation. Chest X-ray revealed lung nodules. Prednisolone was increased, her symptoms settled, and she was discharged with azathioprine. She was readmitted at the end of the same year due to two-day history of right deep vein thrombosis and she later succumbed to methicillin-resistant Staphylococcus aureus sepsis.

Matched MeSH terms: Sepsis
Fulltext Francisella philomiragia bacteremia in an immunocompromised patient: a rare case report

Chua HS, Soh YH, Loong SK, AbuBakar S

Ann Clin Microbiol Antimicrob, 2021 Oct 03;20(1):72.
PMID: 34602092 DOI: 10.1186/s12941-021-00475-2

BACKGROUND: Francisella philomiragia is a very rare opportunistic pathogen of humans which causes protean diseases such as pneumonia and other systemic infections. Subsequent failure of prompt treatment may result in poor prognosis with mortality among infected patients.
CASE PRESENTATION: The present report describes a case of F. philomiragia bacteraemia first reported in Malaysia and Asian in a 60-year-old patient with underlying end-stage renal disease (ESRF) and diabetes mellitus. He presented with Acute Pulmonary Oedema with Non-ST-Elevation Myocardial Infarction (NSTEMI) in our hospital. He was intubated in view of persistent type I respiratory failure and persistent desaturation despite post haemodialysis. Blood investigation indicated the presence of ongoing infection and inflammation. The aerobic blood culture growth of F. philomiragia was identified using the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (Score value: 2.16) and confirmed by 16S Ribosomal DNA (16S rDNA) sequencing. He was discharged well on day 26 of admission, after completing one week of piperacillin/tazobactam and two weeks of doxycycline.
CONCLUSION: Clinical suspicion should be raised if patients with known risk factors are presenting with pneumonia or pulmonary nodules especially as these are the most common manifestations of F. philomiragia infection. Early diagnosis via accurate laboratory identification of the organism through MALDI-TOF mass spectrometry and molecular technique such as 16S rDNA sequencing are vital for prompt treatment that results in better outcomes for the afflicted patients.

Matched MeSH terms: Sepsis

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