Unravelling the therapeutic potential of forkhead box proteins in breast cancer: An update (Review).

Breast cancer, a prominent cause of mortality among women, develops from abnormal growth of breast tissue, thereby rendering it one of the most commonly detected cancers in the female population. Although numerous treatment strategies are available for breast cancer, discordance in terms of effective treatment and response still exists. Recently, the potential of signaling pathways and transcription factors has gained substantial attention in the cancer community; therefore, understanding their role will assist researchers in comprehending the onset and advancement of breast cancer. Forkhead box (FOX) proteins, which are important transcription factors, are considered crucial regulators of various cellular activities, including cell division and proliferation. The present study explored several subclasses of FOX proteins and their possible role in breast carcinogenesis, followed by the interaction between microRNA (miRNA) and FOX proteins. This interaction is implicated in promoting cell infiltration into surrounding tissues, ultimately leading to metastasis. The various roles that FOX proteins play in breast cancer development, their intricate relationships with miRNA, and their involvement in therapeutic resistance highlight the complexity of breast cancer dynamics. Therefore, recognizing the progress and challenges in current treatments is crucial because, despite advancements, persistent disparities in treatment effectiveness underscore the need for ongoing research, with future studies emphasizing the necessity for targeted strategies that account for the multifaceted aspects of breast cancer.

Discovery of novel dihydronaphthalene-imidazole ligands as potential inhibitors of Staphylococcus aureus multidrug resistant NorA efflux pump: A combination of experimental and in silico molecular docking studies.

Overexpression of the efflux pump is a predominant mechanism by which bacteria show antimicrobial resistance (AMR) and leads to the global emergence of multidrug resistance (MDR). In this work, the inhibitory potential of library of dihydronapthyl scaffold-based imidazole derivatives having structural resemblances with some known efflux pump inhibitors (EPI) were designed, synthesized and evaluated against efflux pump inhibitor against overexpressing bacterial strains to study the synergistic effect of compounds and antibiotics. Out of 15 compounds, four compounds (Dz-1, Dz-3, Dz-7, and Dz-8) were found to be highly active. DZ-3 modulated the MIC of ciprofloxacin, erythromycin, and tetracycline by 128-fold each against 1199B, XU212 and RN4220 strains of S. aureus respectively. DZ-3 also potentiated tetracycline by 64-fold in E. coli AG100 strain. DZ-7 modulated the MIC of both tetracycline and erythromycin 128-fold each in S. aureus XU212 and S. aureus RN4220 strains. DZ-1 and DZ-8 showed the moderate reduction in MIC of tetracycline in E. coli AG100 only by 16-fold and 8-fold, respectively. DZ-3 was found to be the potential inhibitor of NorA as determined by ethidium bromide efflux inhibition and accumulation studies employing NorA overexpressing strain SA-1199B. DZ-3 displayed EPI activity at non-cytotoxic concentration to human cells and did not possess any antibacterial activity. Furthermore, molecular docking studies of DZ-3 was carried out in order to understand the possible binding sites of DZ-3 with the active site of the protein. These studies indicate that dihydronaphthalene scaffolds could serve as valuable cores for the development of promising EPIs.

Landfill leachate a new threat to water quality: a case study from the Temperate Himalayas.

Landfills are commonly seen as the most cost-efficient and practical approach to waste management in various regions around the world. Nonetheless, the infiltration of hazardous materials from poorly managed dumping sites remains a significant environmental issue in most developing countries such as India. Leachate serves as a prominent point source of contamination in many environmental media like soil, groundwater, and surface water around the world. So the prime issues humans are experiencing are associated with water quality. Thus, the investigation was undertaken to assess the impact of leachate from the Achan landfill on surface water quality in the Temperate Himalayas. Monitoring was done during in all four seasons, viz., spring, summer, autumn, and winter. Among the sites, the leachate outflow site was found to have the highest mean value of pH (7.95), EC (2.16 dS/m), total nitrogen (2.64 mg/l), P (4.75 mg/l), K (1.41 mg/l), Ca (107.45 mg/l), Mg (54.93 mg/l), Zn (0.8 mg/l), Fe (1.78 mg/l), Cu (0.66 mg/l), Mn (0.81 mg/l), BOD (21.47 mg/l), COD (66.24 mg/l), temperature (14.22 °C), turbidity (14.29 NTU), while lowest mean values of all parameters were recorded at control site. Among the seasons, summer season was found to have maximum value of pH (7.9), EC (2.36 dS/m), total nitrogen (2.54 mg/l), P (4.0 mg/l), K (0.89 mg/l), Ca (85.94 mg/l), Mg (43.91 mg/l), Fe (1.4 mg/l), Cu (0.52 mg/l), Mn (0.64 mg/l), BOD (22.82 mg/l), COD (65.87 mg/l), temperature (18.99 °C), and turbidity (8.49 NTU). The maximum mean value of Zn (0.66 mg/l) was recorded during winter season, while other parameters were found to be minimum during winter season. From this study, we concluded that a decreasing trend was observed during all the seasons in the concentration of all physico-chemical parameters with an increase in distance from the landfill. So it is recommended that the leachate should be treated at the source before disposing into the water body and the landfill should be lined properly to prevent the entry of leachate into water sources.

Physicochemical and Anti-fungal Studies of the Pharmaceutical Co-crystal/Salt of Fluconazole.

Crystal engineering is one green alternative to organic synthesis that can be used to manipulate molecular behavior promptly and economically. We report the preparation and characterization of the pharmaceutical organic salt (FLC-C) of fluconazole (FLC) and organosulfonate (NDSA-2H), based on the sulfonate-pyridinium supramolecular synthon. Structural studies validate the crystallization of the two-component stoichiometric crystal with two molecules of water in the triclinic P1̅ space group. The anticipated proton transfer between the crystal forms leads to ionic interactions, augmenting the organic salt's thermal stability. Hirshfeld studies of FLC-C help to understand the role and significance of different types of intermolecular interactions responsible for crystal packing. The structural and theoretical studies indicate the absence of π-π interactions in FLC-C, which account for the incipience of solid-state emission in the product. The solubility studies establish augmented aqueous solubility of FLC-C over pristine FLC at physiological pH values of 2 and 7. Interestingly, in in vitro studies, FLC-C appears to serve as a potential alternative to FLC, displaying a wide spectrum of antifungal activity. FLC-C is active against several human pathogenic yeast strains, including the leading and emerging Candida strains (Candida albicans and Candida auris, respectively), at comparable and/or lower drug concentrations without showing any enhanced host cell toxicity. Interestingly, the pharmaceutical co-crystal also displays fluorescence properties inside the Candida cells.

A distribution-free newsvendor model considering environmental impact and shortages with price-dependent stochastic demand.

In today's competitive and volatile market, demand prediction for seasonal items is a challenging task. The variation in demand is so quick that the retailer cannot face the risk of understocking or overstocking. Unsold items need to discarded, which has environmental implications. It is often difficult to calculate the effects of lost sales on a firm's monetary values, and environmental impact is not a concern to most businesses. These issues concerned with the environmental impact and the shortages are considered in this paper. A single-period inventory mathematical model is formulated to maximize expected profit in a stochastic scenario while calculating the optimal price and order quantity. The demand considered in this model is price-dependent, with several emergency backordering options to overcome the shortages. The demand probability distribution is unknown to the newsvendor problem. The only available demand data are the mean and standard deviation. In this model, the distribution-free method is applied. A numerical example is provided to demonstrate the model's applicability. To prove that this model is robust, sensitivity analysis is performed.

miRNAs and the Hippo pathway in cancer: Exploring the therapeutic potential (Review).

Cancer is recognized as the leading cause of death worldwide. The hippo signaling pathway regulates organ size by balancing cell proliferation and cell death; hence dysregulation of the hippo pathway promotes cancer­like conditions. miRNAs are a type of non­coding RNA that have been shown to regulate gene expression. miRNA levels are altered in various classes of cancer. Researchers have also uncovered a crosslinking between miRNAs and the hippo pathway, which has been linked to cancer. The components of the hippo pathway regulate miRNA synthesis, and various miRNAs regulate the components of the hippo pathway both positively and negatively, which can lead to cancer­like conditions. In the present review article, the mechanism behind the hippo signaling pathway and miRNAs biogenesis and crosslinks between miRNAs and the hippo pathway, which result in cancer, shall be discussed. Furthermore, the article will cover miRNA­related therapeutics and provide an overview of the development of resistance to anticancer drugs. Understanding the underlying processes would improve the chances of developing effective cancer treatment therapies.

Bacterial Endophyte Community Dynamics in Apple (Malus domestica Borkh.) Germplasm and Their Evaluation for Scab Management Strategies.

The large genetic evolution due to the sexual reproduction-mediated gene assortments and propensities has made Venturia inaequalis (causing apple scab) unique with respect to its management strategies. The resistance in apple germplasm against the scab, being controlled for by more than fifteen genes, has limited gene alteration-based investigations. Therefore, a biological approach of bacterial endophyte community dynamics was envisioned across the apple germplasm in context to the fungistatic behavior against V. inaequalis. A total of 155 colonies of bacterial endophytes were isolated from various plant parts of the apple, comprising 19 varieties, and after screening for antifungal behavior followed by morphological, ARDRA, and sequence analysis, a total of 71 isolates were selected for this study. The alpha diversity indices were seen to fluctuate greatly among the isolation samples in context to microflora with antifungal behavior. As all the isolates were screened for the presence of various metabolites and some relevant genes that directly or indirectly influence the fungistatic behavior of the isolated microflora, a huge variation among the isolated microflora was observed. The outstanding isolates showing highest percentage growth inhibition of V. inaequalis were exploited to raise a bio-formulation, which was tested against the scab prevalence in eight apple varieties under controlled growth conditions. The formulation at all the concentrations caused considerable reductions in both the disease severity and disease incidence in all the tested apple varieties. Red Delicious being most important cultivar of the northwestern Himalayas was further investigated for its biochemical behavior in formulation and the investigation revealed different levels of enzyme production, chlorophyll, and sugars against the non-inoculated control.

The Unforeseen Diagnosis: Hyperparathyroidism-Jaw Tumour Syndrome Case Report and Review of the Literature.

Hypercalcaemia and its systemic sequelae are a relatively common finding amongst patients in the field of endocrinology. Primary hyperparathyroidism, a frequent cause of hypercalcaemia, is often seen among middle-aged female patients, typically resulting from an underlying single-gland adenoma. Although patients may present with symptoms (nephrolithiasis, musculoskeletal discomfort, dehydration, or mood disturbance, to name a few), hypercalcaemia is rather frequently identified incidentally. In younger patients, a familial form of primary hyperparathyroidism must be considered, with a positive diagnosis mandating familial screening. Hyperparathyroidism-jaw tumour syndrome is one such autosomal dominant familial disorder, characterised by a mutation in the cell division cycle 73 (CDC73; also known as HRPT-2) tumour suppressor gene. This disorder is characterised by multiple pleiotropic phenomena, including recurrent primary hyperparathyroidism (and the effects of hypercalcaemia), neoplasms (such as uterine, renal, mandibular, and maxillary), and infertility. A patient not conforming to the classic candidacy for primary hyperparathyroidism requires consideration for a familial cause. Case Description. We present a rare diagnostic entity-hyperparathyroidism-jaw tumour (HPT-JT) syndrome-in a 36-year-old female with recurrent primary hyperparathyroidism, frequent nephrolithiasis, and infertility for 18 years prior to the diagnosis. We aim to promote awareness amongst medical professionals of this rare, but nonetheless essential differential diagnosis through a case report and review of the literature. Conclusion. Medical professionals must avoid diagnostic overshadowing and display a low threshold for genetic testing in younger patients with primary hyperparathyroidism. The importance of proper identification extends beyond the patient to their relatives and offspring.

The Utility of Nucleolar Organizer Regions Quantitation in Early Prediction of Lung Neoplastic Transformation.

BACKGROUND:  Cancer burden can be reduced by early detection of early neoplastic changes applying suitable screening methods. This study aimed to assess the utility of nucleolar organizer regions (NORs) quantitation in early prediction of lung neoplastic transformation. METHODOLOGY: This study investigated 200 apparently healthy individuals categorized into two groups; smoking exposed individuals (N=100), and were categorized as cases, and smoking nonexposed (N=100), and were ascertained as controls. Sputum specimen was attained from each participant (paying all indispensable safety precautions and sample adequacy processes).  Results: Out of the 200 volunteers assessed in the present study, mean NORs counts of >2.00 were identified in 16/200(8%) of the study subjects. All 16/16(100%) cases were found with lung epithelial metaplasia (squamous metaplasia). Out of the 100 cases, mean NORs counts of >2.00 were identified in 16/100(16%), hence, all the controls were identified with mean NORs counts of <2.00. The risk of lung cellular proliferative changes associated with smoking exposure are odds ratio (OR) (95% confidence interval, CI) = 39.2485 (2.3199-664.0052), p = 0.0110, z statistic = 2.543. CONCLUSION: NORs count is a simple, specific, cost-effective, and reliable method that can give a quantitative measurement for the risk of lung neoplastic transformation. For at risk-population (tobacco users), it is recommended to perform the argyrophilic NORs (AgNORs) method beside sputum cytology.

The Prognostic Impact of Pulse Pressure in Acute Heart Failure: Insights from the HEARTS Registry.

BACKGROUND: Low pulse pressure predicts long-term mortality in chronic heart failure, but its prognostic value in acute heart failure is less understood. The present study was designed to examine the prognostic value of pulse pressure in acute heart failure. METHODS: Pulse pressure was tested for its impact on short- and long-term mortality in all patients admitted with acute heart failure from October 2009 to December 2010 in eighteen tertiary centers in Saudi Arabia (n = 2609). All comparisons were based on the median value (50 mmHg). Heart failure with reduced ejection fraction was defined as less than 40%. RESULTS: Low pulse pressure was associated with increased short-term mortality in the overall population (OR = 1.61; 95 CI 1.17, 2.22; P 0.004 and OR = 1.51; 95% CI 1.13, 2.01; P = 0.005, for hospital and thirty-day mortality, respectively), and short-term and two-year mortality in the reduced ejection fraction group (OR = 1.81; 95% CI 1.19, 2.74; P = 0.005, OR = 1.69; 95% CI 1.17, 2.45; P = 0.006, and OR = 1.29; 95% CI 1.02, 1.61; P = 0.030 for hospital, thirty-day, and two-year mortality, respectively). This effect remained after adjustment for relevant clinical variables; however, pulse pressure lost its predictive power both for short-term and long-term mortality after the incorporation of systolic blood pressure in the model. Conversely, low pulse pressure was an independent predictor of improved survival at two and three years in heart failure with preserved ejection fraction (OR = 0.43; 95% CI 0.24, 0.78, P = 0.005 and OR = 0.49; 95% CI 0.28, 0.88; P = 0.016, respectively). CONCLUSION: In acute heart failure with reduced ejection fraction, the prognostic value of low pulse pressure was dependent on systolic blood pressure. However, it inversely correlated with long-term survival in heart failure with preserved ejection fraction.

Disruption management in a constrained multi-product imperfect production system.

Over several decades, production and inventory systems have been widely studied in different aspects, but only a few studies have considered the production disruption problem. In production systems, the production may be disrupted by priorly unknown disturbance and the entire manufacturing plan can be distorted. This research introduces a production-disruption model for a multi-product single-stage production-inventory system. First, a mathematical model for the multi-item production-inventory system is developed to maximize the total profit for a single-disruption recovery-time window. The main objective of the proposed model is to obtain the optimal manufacturing batch size for multi-item in the recovery time window so that the total profit is maximized. To maintain the matter of multi-product, budget and space constraints are used. A genetic algorithm and pattern search techniques are employed to solve this model and all randomly generated test results are compared. Some numerical examples and sensitivity analysis are given to explain the effectiveness and advantages of the proposed model. This proposed model offers a recovery plan for managers and decision-makers to make accurate and effective decisions in real time during the production disruption problems.

Nature of Complex Network of Dengue Epidemic as a Scale-Free Network.

OBJECTIVES: Dengue epidemic is a dynamic and complex phenomenon that has gained considerable attention due to its injurious effects. The focus of this study is to statically analyze the nature of the dengue epidemic network in terms of whether it follows the features of a scale-free network or a random network. METHODS: A multifarious network of Aedes aegypti is addressed keeping the viewpoint of a complex system and modelled as a network. The dengue network has been transformed into a one-mode network from a two-mode network by utilizing projection methods. Furthermore, three network features have been analyzed, the power-law, clustering coefficient, and network visualization. In addition, five methods have been applied to calculate the global clustering coefficient. RESULTS: It has been observed that dengue epidemic follows a power-law, with the value of its exponent γ = -2.1. The value of the clustering coefficient is high for dengue cases, as weight of links. The minimum method showed the highest value among the methods used to calculate the coefficient. Network visualization showed the main areas. Moreover, the dengue situation did not remain the same throughout the observed period. CONCLUSIONS: The results showed that the network topology exhibits the features of a scale-free network instead of a random network. Focal hubs are highlighted and the critical period is found. Outcomes are important for the researchers, health officials, and policy makers who deal with arbovirus epidemic diseases. Zika virus and Chikungunya virus can also be modelled and analyzed in this manner.

The prognostic impact of hyperglycemia on clinical outcomes of acute heart failure: Insights from the heart function assessment registry trial in Saudi Arabia.

BACKGROUND: The prognostic impact of hyperglycemia (HG) in acute heart failure (AHF) is controversial. Our aim is to examine the impact of HG on short- and long-term survival in AHF patients. METHODS: Data from the Heart Function Assessment Registry Trial in Saudi Arabia (HEARTS) for patients who had available random blood sugar (RBS) were analyzed. The enrollment period was from October 2009 to December 2010. Comparisons were performed according to the RBS levels on admission as either <11.1 mmol/L or ≥11.1 mmol/L. Primary outcomes were hospital adverse events and short- and long-term mortality rates. RESULTS: A total of 2511 patients were analyzed. Of those, 728 (29%) had HG. Compared to non-HG patients, hyperglycemics had higher rates of hospital, 30-day, and 1-year mortality rates (8.8% vs. 5.6%; p = 0.003, 10.4% vs. 7.2%; p = 0.007, and 21.8% vs. 18.4%; p = 0.04, respectively). There were no differences between the two groups in 2- or 3-year mortality rates. After adjustment for relevant confounders, HG remained an independent predictor for hospital and 30-day mortality [odds ratio (OR) = 1.6; 95% confidence interval (CI) 1.07-2.42; p = 0.021, and OR = 1.55; 95% CI 1.07-2.25; p = 0.02, respectively]. CONCLUSION: HG on admission is independently associated with hospital and short-term mortality in AHF patients. Future research should focus on examining the impact of tight glycemic control on outcomes of AHF patients.

Intensive structured education for type 1 diabetes management using BERTIE: Long-term follow-up to assess impact on glycaemic control and quality of life indices.

AIMS: Bournemouth Type 1 Intensive Education (BERTIE) is a structured education course delivered 1 day a week for 4 weeks for self-management of type 1 diabetes. BERTIE outcomes were analysed to assess long-term effectiveness: primary outcome assessed impact of BERTIE on glycaemic control, secondary outcomes assessed impact on Problem Area in Diabetes (PAID) scale, severe hypoglycaemia and diabetic ketoacidosis incidence (DKA). METHODS: Prospectively collected outcome data from attendees included glycated haemoglobin (HbA1c), PAID, severe hypoglycaemia and DKA incidence recorded pre-course, 6 months and 1 year post-attendance, with HbA1c assessed annually at subsequent clinic visits. RESULTS: Between 1999 and 2015, 524 people attended BERTIE with 5 year follow-up in 316 (60.3%) attendees. HbA1c was reduced from 74 ±â€¯17 mmol/mol (8.9 ±â€¯1.6%) at baseline to 71 ±â€¯15 mmol/mol (8.6 ±â€¯1.4%) at 1 year and 70 ±â€¯15 mmol/mol (8.6 ±â€¯1.3%) at 5 years (p < 0.0001); severe hypoglycaemia incidence reduced from 0.8 ±â€¯2.1 to 0.4 ±â€¯2.2 episodes/person/year at 1 year (p < 0.0001); PAID scale reduced from 23 ±â€¯16 to 15 ±â€¯12 (p < 0.0001) at 1 year; DKA incidence was 0.06 ±â€¯0.34 episodes/person/year pre-course and 0.03 ±â€¯0.21 at 1 year (p = 0.5271). CONCLUSIONS: BERTIE outcome data demonstrate favorable biochemical and psychological outcomes supporting recommendations that structured education be provided to adults with type 1 diabetes.

Atrial Fibrillation in Patients Hospitalized With Heart Failure: Patient Characteristics and Outcomes From the HEARTS Registry.

Effect of atrial fibrillation (AF) on short- and long-term outcomes in heart failure (HF) is controversial. Accordingly, we examined this relationship in a national multicenter project using data from the Hearts Function Assessment Registry Trial in Saudi Arabia that studied the clinical features and outcomes of patients admitted with de novo and acute on chronic HF. Out of 2593 patients with HF, 449 (17.8%) had AF at presentation. Patients with AF were more likely to be males and older (mean age 65.2 ± 15.0 vs 60.5 ± 14.8 years) to have a history of ventricular tachycardia/ventricular fibrillation (3.1% vs 1.9%) or cerebrovascular accident (15.0% vs 8.5%). However, they were less likely to have diabetes (66.0% vs 55.9%) or coronary artery disease (55.6% vs 42.3%). The 1-, 2-, and 3-year crude mortality rates were significantly higher in patients with AF (23.2% vs 18.3%, 27.4% vs 22.3%, and 27.8% vs 23.2%, respectively). However, there was no significant difference in mortality after adjusting for covariates. Thus, in patients admitted with HF, AF upon presentation was not associated with increased mortality.

In-patient Tolvaptan use in SIADH: care audit, therapy observation and outcome analysis.

BACKGROUND: Indications for use of tolvaptan in SIADH-associated hyponatraemia remain controversial. We audited our local guidelines for Tolvaptan use in this situation to review treatment implications including drug safety, hospital admission episode analysis (episodes of liver toxicity, CNS myelinolysis, sodium-related re-admission rates), morbidity; mortality and underlying aetiologies. METHODS: We report a retrospective case series analysis of on-going treatment outcomes (case-note review) for 31 patients (age 73.3 ± 10.5 years, 55% females) consecutively treated with Tolvaptan as in-patient for confirmed SIADH with persistent S/Na+ < 125 mmol/L despite removal of reversible causes and 24-48 h fluid restriction, and include longer-term outcome data (re-treatment/readmissions/mortality) for up to 4 years of follow-up. A minimum of 6 months follow-up data were reviewed unless the patient died before that period. RESULTS: Short-term outcomes were favourable; 94%-achieved treatment targets after a mean of 3.48 ± 2.46 days. There was statistically significant rise in S/Na+ level after Tolvaptan treatment (before treatment: mean sodium 117.8 ± 3.73, 108-121 mmol/L and after treatment: mean sodium 128.7 ± 3.67, 125-135.2 mmol/L, P < .001). Although the target S/Na+ level was >125 mmol/L in fact one third (35%) of the patients achieved a S/Na+ level of >130 mmol/L by the time of hospital discharge. No patient experienced S/Na+ rise >12 mmol/L/24 h, drug-associated liver injury or CNS-myelinolysis. The average length of hospital stay following start of Tolvaptan treatment was 3.2 days. Relapse of hyponatraemia occurred in 26% of the patients, requiring retreatment with Tolvaptan. In all patients where either relapse of hyponatraemia occurred or readmission was necessary, SIADH was associated with malignancy, which was present overall in 60% of the group studied. CONCLUSIONS: This study confirms the safety and efficacy of Tolvaptan in the treatment of SIADH-related significant, symptomatic hyponatraemia when used under specialist guidance and strict monitoring. A sodium level relapsing below the treatment threshold by 1 week after discontinuation is a good indicator of a patient group with re-treatment/longer-term therapy needs, all of whom had underlying malignancy. The criteria set locally in our trust to initiate Tolvaptan use also identifies a group where further investigation for underlying malignancy should be considered.

Cyclical Cushing's: how best to catch the ups and downs.

A 68-year-old man with a background of hypertension and type 2 diabetes presented with fluctuating symptoms of muscle aches and pains and tiredness. His initial work-up for the possibility of hypercortisolaemia showed a completely variable pattern, with 24-hour cortisol excretion and serum cortisol post 1 mg dexamethasone suppression test ranging from normal to significantly elevated. A series of salivary cortisol with symptom diary confirmed the cyclical nature of hypercortisolaemia, and his concomitant adrenocorticotropic hormone (ACTH) levels were elevated. An inferior petrosal sinus sampling, performed during hypercortisolaemic phase of his cycle,suggested a central source of ACTH secretion. He had unsuccessful exploration of his pituitary and was eventually treated with bilateral adrenalectomy followed by lifelong steroid replacement. His symptoms improved immediately, and he came off his oral hypoglycaemic and antihypertensive agents within 6 months following his surgery.

Worsening heart failure in 'real-world' clinical practice: predictors and prognostic impact.

AIMS: The aim of this study was to compare the clinical features, predictors, and clinical outcomes of patients hospitalized with acute heart failure (AHF), with and without worsening heart failure (WHF). METHODS AND RESULTS: We used data from a multicentre prospective registry of AHF patients created in Saudi Arabia. WHF was defined as recurrence of heart failure symptoms or signs-with or without cardiogenic shock. In-hospital short- and long-term outcomes, as well as predictors of WHF are described. Of the 2609 AHF patients enrolled, 33.8% developed WHF. WHF patients were more likely to have a history of heart failure and ischaemic heart disease. Use of intravenous vasodilators, inotropic agents, furosemide infusions, and discharge beta-blockers was significantly higher in WHF patients, while use of discharge ACE inhibitors was higher in patients without WHF. Length of hospital stay was significantly longer for WHF patients than for those without WHF [median (interquartile range) 13 (14) vs. 7 (7) days, P < 0.001]. In-hospital, 30-day, 1-year, and 2-year mortality rates were higher in WHF patients than in non-WHF patients. The adjusted odds ratios for in-hospital, 30-day, and 1-year mortality were 4.13 [95% confidence interval (CI) 2.74-6.20, P < 0.001], 3.17 (95% CI 2.21-4.56, P < 0.001), and 1.34 (95% CI 1.04-1.71, P = 0.021), respectively. The strongest predictors for WHF were having ischaemic cardiomyopathy, AHF with concomitant acute coronary syndrome, and low haemoglobin. CONCLUSION: In real-world clinical practice, WHF during hospitalization for AHF is a strong predictor for short- and intermediate-term mortality, and a cause for longer hospital stays.

Fever of unknown origin in a patient initially presenting with traveller's diarrhoea.

A 17-year-old male presented with diarrhoea and malaise following his return from Kenya and Tunisia. He was managed as a case of traveller's diarrhoea. Stool cultures were negative for pathogenic bacterial growth. Two weeks later he presented with worsening lower back pain. MRI of lumbosacral spine suggested L1 osteomyelitis. CT-guided spinal aspirate grew no organisms and repeat viral serology and blood cultures (including tuberculosis screening) were negative. He was treated with a 6-week course of ceftriaxone. Back pain did not improve and a repeat MRI scan 8 weeks after his antibiotic course indicated progressive changes in L1 extending to L2 with an intradiscal abscess. Repeat CT-guided spinal aspirate grew Salmonella arizonae sensitive to cotrimoxazole and ceftriaxone. He was treated with intravenous ceftriaxone and cotrimoxazole for 12 weeks. A 4-month follow-up MRI scan showed progressive improvement of the L1/L2 discitis with resolution of intradiscal fluid.