Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as mortality predictor of advanced stage non-small cell lung cancer (NSCLC) with COVID-19 in Indonesia.

OBJECTIVE: This study aimed to compare the mortality rate between advanced-stage non-small cell lung cancer patients (NSCLC) with and without COVID-19. This study also explores the possible laboratory characteristics used for prognostication in patients with NSCLC and COVID-19. Additionally, this study evaluated potential differences in laboratory values between the case and control groups. PATIENTS AND METHODS: This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia, enrolling patients with NSCLC undergoing chemotherapy or targeted therapy between May 2020 and January 2021. All patients with NSCLC and COVID-19 in these periods were enrolled into the case group. The control group was age-matched NSCLC patients without COVID-19 that was derived from the NSCLC cohort through randomization. RESULTS: There were 342 patients with NSCLC between May 2020 and January 2021. Twenty-seven (7.9%) of the patients were infected by COVID-19. To facilitate comparison, thirty-five age-matched controls with NSCLC were selected from the cohort. The mortality rate in patients with COVID-19 was 46.2%. Eleven patients (40.7%) had severe COVID-19, of which none survived. NLR >8.35 has a sensitivity of 83.3%, specificity of 92.9%, LR+ of 12, and LR- of 0.18. The AUC was 0.946 (95% CI 0.867-1.000), p<0.001. PLR >29.14 has a sensitivity of 75.0%, specificity of 71.4%, LR+ 2.62, LR- 0.35, and AUC 0.851 (95% CI 0.706-0.996), p=0.002. Both NLR and PLR were associated with shorter time-to-mortality in the unadjusted and adjusted model CONCLUSIONS: NLR and PLR are independent predictors of mortality in COVID-19 patients with NSCLC.

Validation and clinical implications of the IDSA/ATS minor criteria for severe community-acquired pneumonia.

BACKGROUND: The 2007 Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) guidelines defined severe community-acquired pneumonia (CAP) and recommended intensive care unit (ICU) admission when patients fulfilled three out of nine minor criteria. These criteria have not been validated. METHODS: All patients admitted to our hospital from 2004 to 2007 for CAP were reviewed retrospectively. Patients who fulfilled any IDSA/ATS major criteria for severe CAP at the emergency department (ie, the need for mechanical ventilation or vasopressors) were excluded. The predictive characteristics of the IDSA/ATS minor criteria were compared with those of the Pneumonia Severity Index (PSI) and the CURB-65 score for hospital mortality and ICU admission. RESULTS: 1242 patients were studied (mean age 65.7 years, hospital mortality 14.7%). The areas under the receiver operating characteristic curves for the IDSA/ATS minor criteria were 0.88 (95% CI 0.86 to 0.91) and 0.85 (95% CI 0.81 to 0.88) for predicting hospital mortality and ICU admission, respectively. These were greater than the corresponding areas for the PSI and the CURB-65 score (p < 0.05). The sensitivity, specificity, positive and negative predictive values of the minor criteria were 81.4%, 82.9%, 45.2% and 96.3%, respectively, for hospital mortality and 58.3%, 90.6%, 52.9% and 92.3%, respectively, for ICU admission. The minor criteria were more specific than the PSI and more sensitive than the CURB-65 score for both outcomes. CONCLUSION: These findings support the use of the IDSA/ATS minor criteria to predict hospital mortality and guide ICU admission in inpatients with CAP who do not require emergency mechanical ventilation or vasopressors.

Variance analysis applied to a stroke pathway: how this can improve efficiency of healthcare delivery.

INTRODUCTION: Stroke is a complicated disease that requires a multidisciplinary approach for its management. We postulated that variance analysis applied to a stroke pathway, by identifying major problem areas and encouraging timely corrective actions, would lead to more efficient healthcare delivery to hospitalised stroke patients. MATERIALS AND METHODS: Prospectively collected variance data from consecutive stroke patients discharged from a tertiary hospital in Singapore during a 3-month period in 2000 were used to identify the major variances causing increased length of stay. These were compared and contrasted to variance data collected during the same 3-month period in the subsequent year (2001), after the implementation of stroke pathway and the availability of monthly variance analysis reports. Patient characteristics and outcome measures were also compared between the two study periods. RESULTS: The four major variances that accounted for increased length of stay were, in descending order of the number of patients affected, awaiting bed availability in step-down facilities, delay in head computed tomographic scan performance, awaiting family's decision on discharge plan and incomplete application submitted to step-down facilities. After implementation of the stroke pathway with ongoing variance analysis, all four variances showed different extent of improvements. There were no significant differences in patient characteristics between the two study periods, whereas the average length of stay significantly diminished in the late study period with a trend for decreased in-hospital mortality, compared to the early study period. CONCLUSION: Variance analysis applied in the context of a stroke pathway was effective in identifying major variances causing increased length of stay. This allowed targeted intervention to improve efficiency of healthcare delivery to stroke patients.

Stroke disease management--a framework for comprehensive stroke care.

Disease management is an approach to patient care that coordinates medical resources for the patient across the entire healthcare delivery system throughout the lifetime of the patient with the disease. Stroke is suitable for disease management as it is a well-known disease with a high prevalence, high cost, variable practice pattern, poor clinical outcome, and managed by a non-integrated healthcare system. It has measurable and actionable outcomes, with available local expertise and support of the Ministry of Health. Developing the programme requires a multidisciplinary team, baseline data on target populations and healthcare services, identification of core components, collaboration with key stakeholders, development of evidence-based clinical practice guidelines and carepaths, institution of care coordinators, use of information technology and continuous quality improvement to produce an effective plan. Core components include public education, risk factor screening and management, primary care and specialist clinics, acute stroke units, inpatient and outpatient rehabilitation facilities, and supportive community services including medical, nursing, therapy, home help and support groups for patients and carers. The family physician plays a key role. Coordination of services is best done by a network of hospital and community-based care managers, and is enhanced by a coordinating call centre. Continuous quality improvement is required, with audit of processes and outcomes, facilitated by a disease registry. Pitfalls include inappropriate exclusion of deserving patients, misuse, loss of physician and patient independence, over-estimation of benefits, and care fragmentation. Collaboration and cooperative among all parties will help ensure a successful and sustainable programme.

Proton transfer from histidine 244 may facilitate the 1,2 rearrangement reaction in coenzyme B(12)-dependent methylmalonyl-CoA mutase.

Methylmalonyl-CoA mutase is an adenosylcobalamin-dependent enzyme that catalyzes the 1,2 rearrangement of methylmalonyl-CoA to succinyl-CoA. This reaction results in the interchange of a carbonyl-CoA group and a hydrogen atom on vicinal carbons. The crystal structure of the enzyme reveals the presence of an aromatic cluster of residues in the active site that includes His-244, Tyr-243, and Tyr-89 in the large subunit. Of these, His-244 is within hydrogen bonding distance to the carbonyl oxygen of the carbonyl-CoA moiety of the substrate. The location of these aromatic residues suggests a possible role for them in catalysis either in radical stabilization and/or by direct participation in one or more steps in the reaction. The mechanism by which the initially formed substrate radical isomerizes to the product radical during the rearrangement of methylmalonyl-CoA to succinyl-CoA is unknown. Ab initio molecular orbital theory calculations predict that partial proton transfer can contribute significantly to the lowering of the barrier for the rearrangement reaction. In this study, we report the kinetic characterization of the H244G mutant, which results in an acute sensitivity of the enzyme to oxygen, indicating the important role of this residue in radical stabilization. Mutation of His-244 leads to an approximately 300-fold lowering in the catalytic efficiency of the enzyme and loss of one of the two titratable pK(a) values that govern the activity of the wild type enzyme. These data suggest that protonation of His-244 increases the reaction rate in wild type enzyme and provides experimental support for ab initio molecular orbital theory calculations that predict rate enhancement of the rearrangement reaction by the interaction of the migrating group with a general acid. However, the magnitude of the rate enhancement is significantly lower than that predicted by the theoretical studies.

Assignment of enzymatic functions to specific regions of the PLP-dependent heme protein cystathionine beta-synthase.

Cystathionine beta-synthase is a unique heme protein that catalyzes a pyridoxal phosphate (or PLP)-dependent beta-replacement reaction. The reaction involves the condensation of serine and homocysteine and constitutes one of the two major avenues for detoxification of homocysteine in mammals. The enzyme is allosterically regulated by S-adenosylmethionine (AdoMet). In this study, we have characterized the kinetic, spectroscopic, and ligand binding properties of a truncated catalytic core of cystathionine beta-synthase extending from residues 1 through 408 in which the C-terminal 143 residues have been deleted. This is similar to a natural variant of the protein that has been described in a homocystinuric patient in which the predicted peptide is 419 amino acids in length. Truncation leads to the formation of a dimeric enzyme in contrast to the tetrameric organization of the native enzyme. Some of the kinetic properties of the truncated enzyme are different from the full-length form, most notably, significantly higher K(m)s for the two substrates, and loss of activation by AdoMet. This is paralleled by the absence of AdoMet binding to the truncated form, whereas four AdoMet molecules bind cooperatively to the full-length tetrameric enzyme with a K(d) of 7. 4 microM. Steady-state kinetic analysis indicates that the order of substrate addition is important. Thus, preincubation of the enzyme with homocysteine leads to a 2-fold increase in V(max) relative to preincubation of the enzyme with serine. Since the intracellular concentration of serine is significantly greater than that of homocysteine, the physiological significance of this phenomenon needs to be considered. Based on ligand binding studies and homology searches with protein sequences in the database, we assign residues 68-209 as being important for PLP binding, residues 241-341 for heme binding, and residues 421-469 for AdoMet binding.