Bile acid indices as biomarkers for liver diseases I: Diagnostic markers

BACKGROUNDHepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis.AIMTo discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA profile.METHODSWe analyzed urine samples by liquid chromatography-tandem mass spectrometry and compared the urinary BA profile between 300 patients with hepatobiliary diseases vs 103 healthy controls by statistical analysis. The BA profile was characterized using BA indices, which quantifies the composition, metabolism, hydrophilicity, and toxicity of the BA profile. BA indices have much lower inter- and intra-individual variability compared to absolute concentrations of BA. In addition, BA indices demonstrate high area under the receiver operating characteristic curves, and changes of BA indices are associated with the risk of having a liver disease, which demonstrates their use as diagnostic biomarkers for cholestatic liver diseases.RESULTSTotal and individual BA concentrations were higher in all patients. The percentage of secondary BA (lithocholic acid and deoxycholic acid) was significantly lower, while the percentage of primary BA (chenodeoxycholic acid, cholic acid, and hyocholic acid) was markedly higher in patients compared to controls. In addition, the percentage of taurine-amidation was higher in patients than controls. The increase in the non-12α-OH BA was more profound than 12α-OH BA (cholic acid and deoxycholic acid) causing a decrease in the 12α-OH/ non-12α-OH ratio in patients. This trend was stronger in patients with more advanced liver diseases as reflected by the model for end-stage liver disease score and the presence of hepatic decompensation. The percentage of sulfation was also higher in patients with more severe forms of liver diseases.CONCLUSIONBA indices have much lower inter- and intra-individual variability compared to absolute BA concentrations and changes of BA indices are associated with the risk of developing liver diseases.     

A clinical and microbiological study of puerperal sepsis in a tertiary care hospital in India

Objective: This prospective study was carried out to evaluate the clinical profile and bacterial isolates among women with puerperal sepsis in a tertiary hospital in North India.

Materials and methods: Women with puerperal sepsis (n?=?45) admitted from January 2015 to April 2016 were followed prospectively. Cultures were obtained from cervix, blood, urine, and pyoperitoneum. Initial antibiotics were cefotaxime or piperacillin with tazobactam plus amikacin plus clindamycin or metronidazole and were changed according to sensitivity.

Results: Out of 7887 deliveries during this period, 45 (0.2%) women had puerperal sepsis. 16 (35.5%) delivered in the present hospital, 25 (55.5%) at another health care facility, and 4 (8.9%) at home. Delivery was by cesarean section (CS) in 24/45 (53.3%) and vaginal in 21/45 (46.6%). Grade 1 sepsis occurred in 21, grade 2 in two, and grade 3 in 22 women. Majority (29/45 or 64.5%) had no risk factor for puerperal sepsis. There were two (4.4%) deaths and 13/45 (28.8%) had near-miss morbidity. Pathogenic bacteria were isolated in 33/45 (73.3%) in cervical swab (69%), blood, urine, or pus culture with no significant difference in the bacterial yield or species isolated between cotton or polyester swabs (p?>?.05). Escherichia coli were the commonest isolate and was sensitive to amikacin in all. Five had stillbirths and 4/40 neonates developed sepsis but recovered.

Conclusions: Escherichia coli was the commonest pathogen and was uniformly sensitive to amikacin, which may be included among the initial antibiotics to treat puerperal sepsis in India.     

Prediction of early (4-week) mortality in acute myeloid leukemia with intensive chemotherapy

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m² during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15-99). Among them, 442 patients (12%) had core-binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and -Y, and pneumonia as adverse prognostic factors for an early 4-week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4-week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low-, high-, and very high-risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.     

Validation of the language component of the Addenbrooke's Cognitive Examination – Revised (ACE‐R) as a screening tool for aphasia in stroke patients

Aim: Several tests are available for aphasia screening following stroke. However, some of them have shortcomings such as need of specialist knowledge, low sensitivity and/or specificity and lengthy administration time. Our study aims to evaluate the language component of the Addenbrooke's Cognitive Examination – Revised (ACE‐R) as a screening tool for aphasia in stroke patients. Methods: The language component of ACE‐R was administered to consecutive patients admitted to a post‐acute stroke unit. Patients who were medically unstable or had a significant history of sensory impairment or mental health issues were excluded. The test was administered by two junior doctors with basic training in ACE‐R administration. Patients recruited were also assessed by an experienced speech and language therapist (SLT). The results of the two assessments were documented by a different member of the team and the SLT results were used as the benchmark to calculate the ACE‐R language component sensitivity and specificity. Results: Fifty‐nine participants were recruited and 27 of them were women. The mean age was 72 (SD 11.9). Thirty‐four participants had left and 11 right hemisphere stroke. Fourteen had bilateral affection. Six participants were left handed. A cut‐off value of 22/26 of ACE‐R language component showed 100% specificity and 83.1% sensitivity, while a cut‐off value of 16/26 had 88.2% specificity and 100% sensitivity. Conclusion: Our results suggest that the language component of ACE‐R has a satisfactory sensitivity and specificity compared with other screening tests used in strokes. It is easy to administer and free to use.     

Therapy of Core Binding Factor Acute Myeloid Leukemia: Incremental Improvements Toward Better Long-Term Results

BackgroundDespite being considered as good prognostic acute myelogenous leukemia (AML), the long-term survival rate in core binding factor (CBF) AML leaves room for substantial improvement.Materials and MethodsWe reviewed relevant English language literature related to treatment of CBF AML available in PubMed. Review also included meeting abstracts.ResultsMulticycle high dose cytarabine in consolidation improves remission duration but larger groups report overall survival in the range of 40% to 50% at 5 years or longer.ConclusionsConcerted effort is needed toward improving outcomes in CBF AML through clinical trials and risk-adapted approach.