Impact of spatial separation for respiratory patients on emergency department flow process intervals and length of stay.

BACKGROUND: Spatial separation in emergency departments (EDs) is empirically practised as part of transmission-based precaution. Despite its potential benefits in segregating potentially infectious patients, the effects of spatial separation on patient flow remain uncertain. AIM: To explore the impact of spatial separation on ED patient flow and to identify specific clinical factors and flow process intervals (FPIs) influencing ED length of stay (EDLOS). METHODS: This was a retrospective study of data extracted from patients' electronic medical records from January 1st to March 31st, 2022 conducted at the ED of a tertiary hospital in Kuala Lumpur, Malaysia. During this period, patients were separated into respiratory areas (RA) and non-respiratory areas (NRA) based on Centers for Disease Control and Prevention recommendations. The study obtained ethics approval from the institution's ethics board. FINDINGS: A total of 1054 patients were included in the study, 275 allocated to RA and 779 to NRA. Patients in RA had a significantly longer median EDLOS compared with NRA (9 h 29 min vs 7 h 6 min, P < 0.001, d = 0.41). A lower proportion of patients in RA achieved an EDLOS ≤8 h compared to NRA (41.8% vs 58.3%, P < 0.001). Independent factors affecting EDLOS were: triage category; re-triaging; hypertension; performing biomedical imaging; medical, surgical, and critical care consultations; and disposition plan. Bottlenecks significantly prolonging EDLOS were decision-to-departure, ultrasound interval, and referral-to-consultation. CONCLUSION: Spatial separation prolongs FPIs and EDLOS. Addressing inpatient access block and streamlining specialty review and biomedical imaging processes may reduce RA EDLOS.

Knowledge and perception of equine ticks and tick-borne diseases of Pennsylvania horse owners and caretakers.

There is limited data on current knowledge of Pennsylvania horse caretakers on tick-borne diseases (TBDs), tick identification, and tick management practices. This study aimed to determine tick knowledge, concern, and management among Pennsylvania equine caretakers using an online survey. Descriptive statistics and one-way ANOVA tests were used to analyze data. The survey received 894 responses (539 completed) from Pennsylvania equine owners and caretakers. The largest proportion of respondents cared for 3-5 horses (31 %), followed by 2 horses (27 %). Veterinarian-confirmed diagnosis rates of two TBDs, Lyme disease and anaplasmosis, were 38 % and 22 %, respectively. Most respondents (39 %) were moderately confident in recognizing Lyme disease, while most (44 %) were not confident at all in recognizing anaplasmosis. Most respondents (69 %) were either extremely or very concerned about their horses contracting any TBDs. Tick bite and TBD prevention methods used by equine caretakers included performing tick checks, using on-animal repellents, and conducting pasture/landscape management. Ten knowledge-based questions were asked, and the mean correct score was 3.97 ± 2.18 out of 10 possible points. There were significant positive associations between higher knowledge scores and previous veterinarian-confirmed equine Lyme disease diagnosis, higher concern level of TBDs, and higher frequency of tick checks. With increased equine TBD prevalence and high levels of horse owner concern about TBD, Extension educators should focus on teaching about TBDs and managing ticks on horses and farms.

Transfusion medicine knowledge among clinicians at a teaching hospital in Malaysia.

INTRODUCTION: Inappropriate use of blood and blood products has been well reported from many countries including Malaysia and may be due to a deficit of transfusion medicine (TM) knowledge. This study is aimed to assess TM knowledge among clinicians in a tertiary hospital. MATERIALS AND METHODS: The validated exam developed by the BEST collaborative group was used to assess TM knowledge of doctors, from junior residents up to senior specialists. Scores of 42%, 62%, and 82%, corresponding to basic, intermediate, and expert levels of knowledge, respectively. Convenience sampling was done from eight blood-using departments at University Malaya Medical Centre. The Kruskal-Wallis test was used to compare the candidates' exam scores between different variables. RESULTS: A total of 184 doctors were assessed. The overall mean score was 40.1% (SD 12.7%). The most senior doctors had a significantly lower mean score compared with resident trainees and specialists. Doctors from haematology, anesthesiology, and internal medicine had significantly higher scores (51%, 47.4%, and 46.4% respectively, p<0.05). No correlations were found between the exam scores and the self-reported amount, or quality of prior TM teaching, nor with the year of postgraduate training. Participants did poorly on questions related to transfusion reactions, especially the question on transfusion-related acute lung injury. CONCLUSION: Inadequate transfusion medicine knowledge was found across all the departments and levels of appointment. It is concerning that the most senior decision-making doctors had especially poor knowledge. TM training is needed by all residents, and regular updates should be given to established specialists.

Primary anorectal malignant melanoma: A clinical, radiology and pathology correlation.

INTRODUCTION: Primary gastrointestinal melanomas are mucosal malignancies that arise from melanocytes in the oropharynx, rectum, and anus. Anorectal malignant melanoma (ARMM) are exceedingly rare, accounting for less than 1% of all melanomas, 0.1% of all rectal malignancies and 4% of anal malignancies. Diagnosis is frequently delayed as these lesions are often mistaken for haemorrhoids. Histological evaluation with special immunohistochemical stains is often necessary for definitive diagnosis. Due to the aggressive nature, 61% of patients with ARMM would already have lymph node involvement or distant metastases, by the time of diagnosis. Prognosis is usually poor with 5-year survival rate of <20%. We report a case of metastatic ARMM in an elderly lady who presented with symptoms and signs mimicking a haemorrhoid. CASE REPORT: A 69-year-old lady presented with one year history of intermittent rectal bleed and an anorectal mass that was initially treated as haemorrhoid. Colonoscopy showed a hyperpigmented mass in the anorectal region which was confirmed as malignant melanoma on histopathological examination. Imaging with CT and MRI demonstrated locally advanced tumour with distant metastases to the liver and lung. Patient was referred for palliative management. CONCLUSION: ARMM is a rare malignancy and often presented with non-specific clinical signs. Diagnosis is frequently delayed without high index of suspicion. MRI pelvis is the imaging of choice to assess local extent of disease. Histologic evaluation with special immunohistochemical stains is often necessary for definitive diagnosis. Prognosis is poor despite surgical and chemotherapeutic interventions.

Evaluating the ability of the Sodergren score to guide the management of internal haemorrhoidal disease.

AIM: The Sodergren score was developed to objectively measure the severity of haemorrhoidal symptoms. This study aimed to determine if there was a difference in the Sodergren score between patients who were offered surgery and patients who underwent successful rubber band ligation of internal haemorrhoidal disease and to assess its performance in guiding management. METHOD: This is a prospective, observational study. The preintervention Sodergren scores of subjects with internal haemorrhoidal disease were recorded and blinded to the surgeon in charge. Sodergren scores of subjects in the two arms were unblinded and compared at the end of the study. RESULTS: The results for 290 patients were available for final analysis. The median scores of those offered surgery and those who underwent successful rubber band ligation differed significantly [4 (interquartile range 3-10) vs 0 (interquartile range 0-4), P = 0.001]. In predicting treatment, the Sodergren score had an area under the receiver operating characteristic curve of 0.735 (95% CI 0.675-0.795). CONCLUSION: There is a significant difference in scores between patients who were offered surgery and patients with successful rubber band ligation. Our study suggests that the Sodergren score has an acceptable discrimination in predicting the need for surgery in internal haemorrhoidal disease. We propose that patients with a Sodergren score of 6 or more be considered for upfront surgery. This score could potentially be used to standardize outcomes of future haemorrhoid trials.

Diagnostic accuracy of pneumonia in Hospital Tuanku Ja'afar Seremban, a tertiary hospital.

OBJECTIVES: The primary objective of this study was to describe the accuracy of pneumonia diagnosis, both community-acquired pneumonia (CAP) and hospitalacquired pneumonia (HAP). Secondary objectives were describing the choice of antibiotics used, pathogens isolated, and predictive parameters in diagnosing pneumonia. METHODS: This was a prospective cross-sectional study to determine the accuracy of the diagnosis of CAP and HAP admitted to Hospital Tuanku Ja'afar. All patients aged ≥12 years admitted to the general medical ward with the diagnosis of CAP or HAP were included in the study. Chest radiograph interpretation was done by certified radiologists. An accurate diagnosis of pneumonia was defined by clinical signs and symptoms of pneumonia supported by radiographical evidence. RESULTS: A total of 159 patients were enrolled into the study from January 2018 to February 2018. Of these only 59(37.1%) cases were accurately diagnosed as pneumonia. Amongst those with pneumonia diagnosis made by the emergency department, medical officers and specialists of medical department; 65.4%, 60% and 47.3% respectively were not pneumonia. Amoxicillin with clavulanate and azithromycin were amongst the most common first choice of antibiotic used (46.5%). In this study, pathogens were isolated either by blood culture or sputum culture in only 20 (12.6%) patients. There was no significant predictive parameter identified in this study, which included white cell counts, Creactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and Pao2/FiO2 ratio. CONCLUSION: About two-thirds of patients diagnosed with pneumonia did not have a compatible radiological finding. Better tools and systems are needed to aid in the diagnosis of pneumonia.

Programmed Ribosomal Frameshifting Mediates Expression of the α-Carboxysome.

Many bacteria employ a protein organelle, the carboxysome, to catalyze carbon dioxide fixation in the Calvin Cycle. Only 10 genes from Halothiobacillus neapolitanus are sufficient for heterologous expression of carboxysomes in Escherichia coli, opening the door to detailed mechanistic analysis of the assembly process of this complex (more than 200MDa). One of these genes, csoS2, has been implicated in assembly but ascribing a molecular function is confounded by the observation that the single csoS2 gene yields expression of two gene products and both display an apparent molecular weight incongruent with the predicted amino acid sequence. Here, we elucidate the co-translational mechanism responsible for the expression of the two protein isoforms. Specifically, csoS2 was found to possess -1 frameshifting elements that lead to the production of the full-length protein, CsoS2B, and a truncated protein, CsoS2A, which possesses a C-terminus translated from the alternate frame. The frameshifting elements comprise both a ribosomal slippery sequence and a 3' secondary structure, and ablation of either sequence is sufficient to eliminate the slip. Using these mutants, we investigated the individual roles of CsoS2B and CsoS2A on carboxysome formation. In this in vivo formation assay, cells expressing only the CsoS2B isoform were capable of producing intact carboxysomes, while those with only CsoS2A were not. Thus, we have answered a long-standing question about the nature of CsoS2 in this model microcompartment and demonstrate that CsoS2B is functionally distinct from CsoS2A in the assembly of α-carboxysomes.

An unusual case of anomalous origin of the right coronary artery and hepatic focal nodular hyperplasia.

Anomalous origin of the right coronary artery (ARCA) and focal nodular hyperplasia (FNH) are frequently reported in association with congenital heart abnormalities but not with each other. We propose that both conditions may share common origins in a maladative hyperplastic response to differential vascular flow due to developmental arterial malformations or aberrant Notch signalling during simultaneous gut and cardiac vasculorigenesis.

The long-term predictive value of the neutrophil-to-lymphocyte ratio in Type 2 diabetic patients presenting with acute myocardial infarction.

BACKGROUND: Patients with diabetes mellitus have worse long-term outcomes after acute myocardial infarction (AMI) than non-diabetics. This may be related to differential contribution of neutrophil and lymphocyte to inflammation during AMI in diabetics vs. non-diabetics. We aim to determine the predictive value of neutrophil-to-lymphocyte ratio (NLR) for major adverse events post-AMI in Type 2 diabetics vs. non-diabetics. METHODS AND RESULTS: A total of 2559 consecutive patients admitted for AMI (61 ± 14 years, 73% male and 43% diabetic) were analyzed. A complete blood count was obtained and the NLR computed for each patient on admission. Across the cohort, the 1-year reinfarction rate was 8.4% (n = 214) and 1-year mortality was 14.5% (n = 370). Univariate determinants of the composite endpoint included age, hypertension, hyperlipidemia, smoking, revascularization and NLR (P < 0.001 for all). The cohort was divided into NLR quartiles. Admission NLR was significantly higher in the diabetic group, 5.2 ± 5.8 vs. 4.6 ± 5.4 (P = 0.007). A step-wise increase in the incidence of the composite endpoint was noted across NLR quartiles for diabetic subjects; hazard ratio (HR) was 2.41 for fourth vs. first quartile (95% confidence interval = 1.63-3.53, P < 0.001). Multivariate analysis of the diabetic group showed that NLR remains as an independent predictor of the composite endpoint (adjusted HR = 1.53, 95% confidence interval = 1.00-2.33, P = 0.048). However, in non-diabetics, HR for NLR was not significant (P = 0.35). CONCLUSION: Increased NLR post-AMI is an independent predictor of major adverse cardiac events in diabetics. Monitoring this easily obtainable new index allows prognostication and risk stratification.

Toxic fibrillar oligomers of amyloid-ß have cross-ß structure.

Although amyloid fibers are found in neurodegenerative diseases, evidence points to soluble oligomers of amyloid-forming proteins as the cytotoxic species. Here, we establish that our preparation of toxic amyloid-ß(1-42) (Abeta42) fibrillar oligomers (TABFOs) shares with mature amyloid fibrils the cross-ß structure, in which adjacent ß-sheets adhere by interpenetration of protein side chains. We study the structure and properties of TABFOs by powder X-ray diffraction, EM, circular dichroism, FTIR spectroscopy, chromatography, conformational antibodies, and celluar toxicity. In TABFOs, Abeta42 molecules stack into short protofilaments consisting of pairs of helical ß-sheets that wrap around each other to form a superhelix. Wrapping results in a hole along the superhelix axis, providing insight into how Abeta may form pathogenic amyloid pores. Our model is consistent with numerous properties of Abeta42 fibrillar oligomers, including heterogenous size, ability to seed new populations of fibrillar oligomers, and fiber-like morphology.

Atomic view of a toxic amyloid small oligomer.

Amyloid diseases, including Alzheimer's, Parkinson's, and the prion conditions, are each associated with a particular protein in fibrillar form. These amyloid fibrils were long suspected to be the disease agents, but evidence suggests that smaller, often transient and polymorphic oligomers are the toxic entities. Here, we identify a segment of the amyloid-forming protein αB crystallin, which forms an oligomeric complex exhibiting properties of other amyloid oligomers: ß-sheet-rich structure, cytotoxicity, and recognition by an oligomer-specific antibody. The x-ray-derived atomic structure of the oligomer reveals a cylindrical barrel, formed from six antiparallel protein strands, that we term a cylindrin. The cylindrin structure is compatible with a sequence segment from the ß-amyloid protein of Alzheimer's disease. Cylindrins offer models for the hitherto elusive structures of amyloid oligomers.

Risk scoring system for prediction of contrast-induced nephropathy in patients with pre-existing renal impairment undergoing percutaneous coronary intervention.

INTRODUCTION: Baseline renal impairment is the most recognised risk factor for development of contrast-induced nephropathy (CIN) post percutaneous coronary intervention (PCI). We examined the additional risk factors in this high-risk group and aimed to develop a risk model for prediction of CIN. METHODS: A cohort of 770 consecutive patients with existing impaired renal function (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2), who received routine prophylactic saline hydration and oral N-acetylcysteine treatment while undergoing PCI between May 2005 to October 2008 in our centre, were enrolled. The study endpoint, CIN, was defined as > 25% increase from baseline creatinine within 48 hours post PCI. RESULTS: Despite routine prophylaxis, CIN occurred in 11.4% of the patients. Important clinical predictors for CIN were age (odds ratio [OR] 1.59, 95% confidence level [CI] 1.0-2.52, p = 0.049), anaemia with haemoglobin < 11 mg/dL (OR 2.26, 95% CI 1.41-3.61, p = 0.001), post-procedure creatinine kinase rise (OR 1.12, 95% CI 1.07-1.16 for every 500 u/L increase, p < 0.001), systolic hypotension with blood pressure < 100 mmHg (OR 2.53, 95% CI 1.16-5.52, p = 0.016) and higher contrast volume. The incidence of CIN was significantly higher in patients with more severe renal failure (6.3%, 17.4% and 40.8% when eGFR was 40-60, 20-40 and < 20 ml/min/1.73 m2 respectively, p < 0.001). A prediction model was developed based on these findings. The incidence of CIN could vary from 2% to > 50% depending on these additional risk profiles. CONCLUSION: Patients with impaired renal function undergoing PCI are at high risk of developing CIN despite traditional prophylaxis. A model of risk prediction could be used to predict its occurrence.

Modularity of a carbon-fixing protein organelle.

Bacterial microcompartments are proteinaceous complexes that catalyze metabolic pathways in a manner reminiscent of organelles. Although microcompartment structure is well understood, much less is known about their assembly and function in vivo. We show here that carboxysomes, CO(2)-fixing microcompartments encoded by 10 genes, can be heterologously produced in Escherichia coli. Expression of carboxysomes in E. coli resulted in the production of icosahedral complexes similar to those from the native host. In vivo, the complexes were capable of both assembling with carboxysomal proteins and fixing CO(2). Characterization of purified synthetic carboxysomes indicated that they were well formed in structure, contained the expected molecular components, and were capable of fixing CO(2) in vitro. In addition, we verify association of the postulated pore-forming protein CsoS1D with the carboxysome and show how it may modulate function. We have developed a genetic system capable of producing modular carbon-fixing microcompartments in a heterologous host. In doing so, we lay the groundwork for understanding these elaborate protein complexes and for the synthetic biological engineering of self-assembling molecular structures.

Ribonuclease A suggests how proteins self-chaperone against amyloid fiber formation.

Genomic analyses have identified segments with high fiber-forming propensity in many proteins not known to form amyloid. Proteins are often protected from entering the amyloid state by molecular chaperones that permit them to fold in isolation from identical molecules; but, how do proteins self-chaperone their folding in the absence of chaperones? Here, we explore this question with the stable protein ribonuclease A (RNase A). We previously identified fiber-forming segments of amyloid-related proteins and demonstrated that insertion of these segments into the C-terminal hinge loop of nonfiber-forming RNase A can convert RNase A into the amyloid state through three-dimensional domain-swapping, where the inserted fiber-forming segments interact to create a steric zipper spine. In this study, we convert RNase A into amyloid-like fibers by increasing the loop length and hence conformational freedom of an endogenous fiber-forming segment, SSTSAASS, in the N-terminal hinge loop. This is accomplished by sandwiching SSTSAASS between inserted Gly residues. With these inserts, SSTSAASS is now able to form the steric zipper spine, allowing RNase A to form amyloid-like fibers. We show that these fibers contain RNase A molecules retaining their enzymatic activity and therefore native-like structure. Thus, RNase A appears to prevent fiber formation by limiting the conformational freedom of this fiber-forming segment from entering a steric zipper. Our observations suggest that proteins have evolved to self-chaperone by using similar protective mechanisms.

Misleading ECG recordings.

Misleading electrocardiogram recordings are not uncommon, and can lead to misdiagnosis. This article highlights two examples and discusses the strategies to recognise them.

Electrocardiography Series. ECGs of structural heart disease: Part 1.

Electrocardiogram (ECG) is a useful but imperfect investigation in the diagnosis and possible follow-up of structural heart disease such as ventricular hypertrophy. Different ECG criteria with different sensitivity and specificity are available to aid the detection of left or right ventricular hypertrophy. Subsequent echocardiography can help in the quantification of ventricular mass and identification of the aetiology.

A cohort study of risk factors and clinical outcome predictors for patients presenting with unstable angina and non ST segment elevation myorardial infraction undergoing coronary intervention.

INTRODUCTION: Thrombolysis in Myocardial Infarction (TIMI) score has been used to predict outcomes in patients presenting with unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI). Our study assessed other clinical predictors for patients with UA/NSTEMI undergoing early percutaneous coronary intervention (PCI). MATERIALS AND METHODS: A cohort of 3822 patients presented with UA/NSTEMI from June 2001 to March 2008 in our center were recruited. Patients underwent PCI during admission. We analyzed the potential risk predictors for major adverse cardiac events (MACE) and death at 1 month and 6 month. RESULTS: Median age was 57.1 +/- 11.1, 78.1 percent men, 34.5 percent had diabetes, 58.8 percent had hypertension. Coronary lesions involving left main and proximal left anterior descending artery was 27.6 percent. 36.1 percent had NSTEMI. Significant predictors for mortality at 6 months were age older than 70 years (p = 0.001, OR = 5.5), female gender (p = 0.001, OR = 2.98), anaemia (p < 0.001 OR = 8.47), baseline renal impairment (P < 0.001, OR = 7.38) and development of contrast nephropathy (CIN) which was defined as 25% or 0.5 mg/dl increase from baseline Creatinine within 48 h after PCI (p = 0.005, OR = 5.8). Diabetes was a predictor of MACE at 6 months (p = 0.003, OR = 1.51) but not mortality. CONCLUSIONS: In patients with UA/NSTEMI, our study showed that MACE and mortality were increased in elderly, female and presence of anaemia. Mortality, but not MACE was increased in chronic renal impairment and development of CIN; while diabetes increased only MACE, but not mortality. SUMMARY: We analyzed a cohort of 3822 patients with UA/NSTEMI underwent PCI and found that elderly, female, presence of anemia, diabetes and chronic renal impairment were high risk predictors for adverse clinical outcome. In addition, development of CIN increased mortality.