Mental health literacy and help-seeking behaviour among Egyptian undergraduates: a cross-sectional national study.

BACKGROUND: Mental health literacy (MHL) and help-seeking behaviors are pivotal in managing mental well-being, especially among Egyptian undergraduates. Despite the importance and prevalent psychological distress in this group, limited research has addressed MHL and associated behaviors in Egypt. This study aimed to assess the levels of MHL and help-seeking behavior among Egyptian university students. METHODS: A cross-sectional study was conducted across ten Egyptian universities during the academic year 2022-2023. A convenience sample of 1740 students was obtained through online questionnaires distributed via social media platforms. The survey comprised demographic characteristics, the Mental Health Literacy Scale (MHLS), and the General Help Seeking Behavior Questionnaire (GHSPQ). RESULTS: Among 1740 Egyptian undergraduates, medical students scored higher in recognizing disorders (p < 0.05), while non-medical students excelled in attitudes (p < 0.05). A strong correlation was observed between attitudes toward mental illness and total mental health literacy (coefficients of 0.664 and 0.657). Univariate analysis indicated a significant association with professional help-seeking (OR = 1.023). Females, individuals aged 21 or above, and non-medical students were more likely to seek mental health information (OR = 1.42, 1.82, 1.55 respectively). Help-seeking behavior for emotional problems was more inclined towards intimate partners, whereas suicidal thoughts prompted seeking professional help. CONCLUSION: The findings advocate for comprehensive mental health education, particularly in rural areas, and emphasis on the role of personal relationships in mental well-being. Implementing these insights could foster improved mental health outcomes and reduce related stigma in Egypt.

Factors influencing poor response to type 2 targeted therapies in severe asthma: a retrospective cohort study.

BACKGROUND: A significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2 targeted therapies, such as benralizumab and omalizumab; have been identified as an effective treatment for severe asthma, improving patient response, lung function tests and asthma symptom control. This study aimed to evaluate factors contributing to poor response to therapy. METHODS: A retrospective single-center cohort study of 162 patients with severe asthma who started biologic therapy; their data were retrieved from medical records for further analysis. Poor responders were patients remained clinically and functionally uncontrolled despite even after augmenting all treatment options. RESULTS: Childhood-onset asthma, bronchiectasis, poor symptom control (ACT below 19), severe airway obstruction (< 60% predicted), and maintenance oral corticosteroid (mOCS) use were significantly associated with poor response to omalizumab and benralizumab; p = 0.0.4 and 0.01; 0.003 and 0.01; 0.01 and 0.001, 0.05 and 0.04; 0.006 and 0.02, respectively. However, chronic rhinosinusitis and IgE < 220kIU/L were associated with higher poor response rates to omalizumab (p = 0.01 and 0.04, respectively). At the same time, female patients and those with blood eosinophils level < 500 cells/mm3 had a higher poor response rate to benralizumab (p = 0.02 and 0.01, respectively). Ischemic heart disease (IHD), bronchiectasis, and continued use of OCS increased the likelihood of poor response to omalizumab by 21, 7, and 24 times (p = 0.004, 0.008, and 0.004, respectively). In contrast, the female gender, childhood-onset asthma and higher BMI increased the likelihood of poor response to benralizumab by 7, 7 and 2 times more, p = 0.03, 0.02 and 0.05, respectively. CONCLUSION: Poor response to omalizumab treatment was independently associated with ischemic heart disease (IHD), bronchiectasis, and a history of maintenance oral corticosteroid (mOCS) use. Conversely, poor response to benralizumab therapy was independently linked to female gender, childhood-onset asthma and higher body mass index (BMI).

Omalizumab Transitions in Severe Asthma: Factors Influencing Switching Decisions and Timing for Optimal Response.

OBJECTIVE: The objective of this study was to assess the effectiveness of switching from omalizumab to another biologic therapy for patients with severe asthma and evaluate factors that influenced the decision to switch and determined the optimal time for a good biologic response. SUBJECTS AND METHODS: A retrospective study of severe asthma patients was conducted at Al-Rashed Allergy Center, a tertiary center in Kuwait. After meeting the eligibility criteria, patients were divided into two comparative groups: those continuing with omalizumab and those who started with omalizumab but switched to another biologic. RESULTS: One hundred sixteen patients with severe asthma were recruited, and only 33 had access to multiple biological treatments. Approximately 22.4% switched from omalizumab. Male patients with a history of ischemic heart disease, chronic rhinosinusitis, and nasal polyps were more likely to switch if they had higher levels of eosinophils in the sputum. This study showed that every 1% increase in sputum eosinophils doubled the likelihood of a switch. Patients with access to alternative biological options had a much shorter mean duration of omalizumab therapy before switching compared to those with only affordable omalizumab: 4.9 ± 1.5 years versus 8.9 ± 1.3 years (p < 0.001). The optimal time to predict the likelihood of a good response was less than 5.5 years, with an area under the curve of 0.91 and p = 0.003. This cutoff point provided a sensitivity and specificity of approximately 89% and 100%, respectively. CONCLUSION: An early transition from omalizumab, specifically within the first 5 years of treatment, in patients with severe asthma and higher sputum eosinophils may enhance the likelihood of a good response if other biological therapies were available.

Comparative Evaluation of Twin Block Appliance and Fixed Orthodontic Appliance in Early Class II Malocclusion Treatment: A Randomized Controlled Trial.

AIMS: To compare skeletal, dentoalveolar, and soft tissue changes between Twin block and early fixed orthodontic appliance for class II division 1 malocclusion treatment through a randomized controlled trial. MATERIALS AND METHODS: Sample and randomization: This study was a randomized controlled trial with a 1:1 allocation ratio in which 40 patients were divided equally into two groups: control and experimental; each group had an equal number of boys and girls. Randomization was achieved using random blocks of 20 patients with allocation concealed in sequentially numbered, opaque, and sealed envelopes. Blinding was only applicable for data analysis of radiographic measurements. Intervention: Twin block appliance was used in the experimental group for 1 year. However, control group was treated with fixed appliance. Inclusion criteria: Skeletal class II division 1 malocclusion with mandibular retrognathism; cephalometric angular measurements: SNA ≥ 82, SNB ≤ 78, ANB ≥ 4; overjet ≥6 mm; and patient in circumpubertal stage cervical vertebral maturation (CVM2 and CVM3). Parameters for evaluation: Cephalometric skeletal, dental, and soft tissue angular and linear measurements were used for evaluation. RESULTS: SNB increased remarkably by 4° in the Twin block group, but only by 0.68 in the control group. There was a significant decrease in vertical dimensions (SN-GoGn) in the Twin block group compared to control group (p = 0.002). Significant enhancement in the facial profile of the patients was observed. CONCLUSIONS: The Twin block appliance induced significant skeletal and dental changes. These changes were more obvious relative to the slight changes induced by natural growth. CLINICAL SIGNIFICANCE: Early treatment of Class II due to mandibular retrusion with Twin block functional appliance is recommended due to its favourable skeletal effect. Early treatment with fixed appliance affects mainly the dentoalveolar component. Long term follow-up is needed for further insights.

Novel 2,4-disubstituted quinazoline analogs as antibacterial agents with improved cytotoxicity profile: Optimization of the 2,4-substituents.

The emergence of bacterial resistance has triggered a multitude of efforts to develop new antibacterial agents. There are many compounds in literature that were reported as potent antibacterial agents, however, they lacked the required safety to mammalian cells or no clear picture about their toxicity profile was presented. Inspired by discovered hit from our in-house library and by previously reported 2,4-diaminosubstituted quinazolines, we describe the design and synthesis of novel 2,4-disubstituted-thioquinazolines (3-13 and 36), 2-thio-4-amino substituted quinazolines (14-33) and 6-substituted 2,4-diamonsubstituted quinazolines (37-39). The synthesized compounds showed potent antibacterial activity against a panel of Gram-positive, efflux deficient E.coli and Mycobacterium smegmatis. The panel also involved resistant strains including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Enterococcus faecium, in addition to Mycobacterium smegmatis. The newly synthesized compounds revealed MIC values against the tested strains ranging from 1 to 64 µg/mL with a good safety profile. Most of the 2-thio-4-amino substituted-quinazolines showed significant antimycobacterial activity with the variations at position 2 and 4 offering additional antibacterial activity against the different strains. Compared to previously reported 2,4-diaminosubstituted quinazolines, the bioisosteric replacement of the 2-amino with sulfur offered a successful approach to keep the high antibacterial potency while substantially improving safety profile as indicated by the reduced activity on different cell lines and a lack of hemolytic activity.

Synthesis and in vitro investigation of novel cytotoxic pyrimidine and pyrazolopyrimidne derivatives showing apoptotic effect.

A series of novel derivatives of hydrazinylpyrimidines, pyrazolylpyrimidines and 3-amino[3,4-d]pyrazolopyrimidines have been synthesized and tested for their in vitro cytotoxic activity against 60 tumor cell lines by NCI. The in vitro cytotoxic IC50 values for the most active compounds were determined against the colon-KM12 cell line (5d, 7c and 7d), breast-MCF-7 (6a) and melanoma-MDA-MB-435 (6h) using 5-fluorouracil (5-FU) as a positive control. Derivatives 5d and 7c were found to be the most potent derivatives against KM12 cell line (IC50 = 1.73 and 1.21 µM, respectively) with a high selectivity index (SI) (18.82 and 35.49, respectively) compared to 5-FU (IC50 = 12.26 µM, SI = 1.93). Compounds 5d and 7c were further investigated for their apoptotic behavior in KM12 cell line. The investigations showed the up-regulation of caspase 3/9 and the pro-apoptotic factor Bax. On the other hand, the expression of the anti-apoptotic factor Bcl-2, was down-regulated, as well as its inhibition at a nanomolar concentration. Furthermore, the apoptotic effect for derivatives 5d and 7c in KM12 cells was detected using annexin V-FITC staining method.

New benzenesulfonamide scaffold-based cytotoxic agents: Design, synthesis, cell viability, apoptotic activity and radioactive tracing studies.

A new series of thiazolidinone (5a-g), thiazinone (9a-g) and dithiazepinone (9a-g) heterocycles bearing a benzenesulfonamide scaffold was synthesized. Cytotoxicity of these derivatives was assessed against MCF-7, HepG2, HCT-116 and A549 cancer cell lines and activity was compared to the known cytotoxic agents doxorubicin and 5-FU where the most active compounds displayed better to nearly similar IC50 values to the reference compounds. For assessing selectivity, the most active derivatives against MCF-7, 5b, 5c and 5e, were also assessed against the normal breast cell line MCF-10 A where they demonstrated high selective cytotoxicity to cancerous cells over that to normal cells. Further, the effect of the most active compounds 5b-e on MCF-7 and HepG2 cell cycle phase distribution was assessed and the tested sulfonamide derivatives were found to induce accumulation of cells in the <2n phase. To further confirm apoptosis induction, caspase 8 and 9 levels in MCF-7 and HepG2 were evaluated before and after treatment with compounds 5b-e and were found to be significantly higher after exposure to the test agents. Since 5c was the most active, its effect on the cell cycle regulation was confirmed where it showed inhibition of the CDK2/cyclin E1. Finally, in vivo biodistribution study using radioiodinated-5c revealed a significant uptake and targeting ability into solid tumor in a xenograft mouse model.

A shared comparison of diabetes mellitus and neurodegenerative disorders.

Diabetes mellitus (DM), one of the most prevalent metabolic diseases in the world population, is associated with a number of comorbid conditions including obesity, pancreatic endocrine changes, and renal and cardio-cerebrovascular alterations, coupled with peripheral neuropathy and neurodegenerative disease, some of these disorders are bundled into metabolic syndrome. Type 1 DM (T1DM) is an autoimmune disease that destroys the insulin-secreting islet cells. Type 2 DM (T2DM) is diabetes that is associated with an imbalance in the glucagon/insulin homeostasis that leads to the formation of amyloid deposits in the brain, pancreatic islet cells, and possibly in the kidney glomerulus. There are several layers of molecular pathologic alterations that contribute to the DM metabolic pathophysiology and its associated neuropathic manifestations. In this review, we describe the general signature metabolic features of DM and the cross-talk with neurodegeneration. We will assess the underlying molecular key players associated with DM-induced neuropathic disorders that are associated with both T1DM and T2DM. In this context, we will highlight the role of tau and amyloid protein deposits in the brain as well in the pancreatic islet cells, and possibly in the kidney glomerulus. Furthermore, we will discuss the central role of mitochondria, oxidative stress, and the unfolded protein response in mediating the DM-associated neuropathic degeneration. This study will elucidate the relationship between DM and neurodegeneration which may account for the evolution of other neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease as discussed later.

Comparative lyophilized platelet-rich plasma wafer and powder for wound-healing enhancement: formulation, in vitro and in vivo studies.

Platelet-rich plasma (PRP) accelerates wound healing, as it is an excellent source of growth factors. PRP was separated from whole human blood by centrifugation. PRP powder and wafers were prepared by lyophilization, with the wafers prepared using sodium carboxymethylcellulose (Na CMC). The PRP wafers showed porous structures, as indicated by scanning electron microscopy (SEM) images, and the ability of the wafer to absorb exudates and thus promote wound healing was tested with the hydration capacity test. The platelet count was tested and indicated that the presence of PRP in the wafers had no effect on the platelet count. An antimicrobial activity test was carried out, showing that PRP had antibacterial activity against Gram-negative bacteria. Compared with lyophilized PRP powder and PRP-free wafers, PRP wafers showed the highest percent of wound size reduction on induced wounds in rats. Histopathological examination of rat skin showed that the PRP wafers achieved the shortest healing time, followed by the lyophilized PRP powder and finally the PRP-free wafers. The present study revealed that PRP can be formulated as a wafer, which is a promising pharmaceutical delivery system that can be used for enhanced wound-healing activity and improved the ease of application compared to lyophilized PRP powder.

A shared comparison of diabetes mellitus and neurodegenerative disorders.

Diabetes mellitus (DM) is one of the most common diseases in the world population, associated with obesity, pancreatic endocrine changes, cardiovascular disease, renal glomerular disease, cerebrovascular disease, peripheral neuropathy, neurodegenerative disease, retinal disease, sleep apnea, some of which are bundled into the metabolic syndrome. The main characteristic of this disease is hyperglycemia, and often with albuminuria. Nevertheless, the classic features, with ketoacidosis in the extreme, are only a first layer of description of this condition. The description of the islet cells of the endocrine pancreas was first described by Opie, and the discovery of insulin by tying off the exocrine pancreatic ducts followed. We later find that the ß-cells secrete insulin and glucagon, which synchronously stimulate or suppress glycogenolysis, and that insulin is essential for glucose intake into the cell. There are yet two other layers for our understanding of diabetes and the effects of its dysfunction, which is the basis for understanding the system-wide expression of the disease. We describe the molecular basis for the central nervous system neuropathic diseases that are associated with both Type 1 DM (T1DM) and Type 2 DM (T2DM), but more so with T2DM. T2DM is an autoimmune disease that destroys the insulin secreting islet cells. T2DM is the diabetes that is associated with an imbalance in the glucagon/insulin homeostasis that leads to the formation of amyloid deposits in the brain, pancreatic islet cells, and possibly the kidney glomerulus.

Trans-cinnamaldehyde Modulates Hippocampal Nrf2 Factor and Inhibits Amyloid Beta Aggregation in LPS-Induced Neuroinflammation Mouse Model.

Trans-cinnamaldehyde (CNM) has recently drawn attention due to its potent anti-inflammatory and antioxidant properties. The current study explored the memory enhancing effects of CNM against lipopolysaccharide (LPS)-induced neuroinflammation in mice. CNM and curcumin (a reference antioxidant) were administered at a dose of 50 mg/kg i.p. 3 h after a single LPS injection (0.8 mg/kg, i.p.) and continued daily for 7 days. Our results displayed that CNM and curcumin significantly ameliorated the LPS-induced impairment of learning and memory, neuroinflammation, oxidative stress and neuronal apoptosis. Memory functions and locomotor activity were assessed by Morris water maze, object recognition test and open field test. Both CNM and curcumin activated the nuclear factor erythroid 2 related factor 2 (Nrf2) and restored levels of downstream antioxidant enzymes superoxide dismutase and glutathione-S-transferase (GST) in the hippocampus. They also attenuated LPS-induced increase in hippocampal contents of interleukin-1ß (IL-1ß), malondialdehyde and caspase-3. Immunohistochemistry results showed that both CNM and curcumin reduced Aß1-42 protein accumulation in brain of mice. Remarkably CNM's effect on IL-1ß was less pronounced than curcumin; however it showed higher GST activity and more potent anti-apoptotic and anti-amylodogenic effect. We conclude that, CNM produces its memory enhancing effects through modulation of Nrf2 antioxidant defense in hippocampus, inhibition of neuroinflammation, apoptosis and amyloid protein burden.

"Real-life" Efficacy and Safety Aspects of 4-Year Omalizumab Treatment for Asthma.

OBJECTIVE: To evaluate the long-term efficacy and safety of omalizumab in asthma in a real-life setting. SUBJECTS AND METHODS: This 4-year observational study included 65 patients treated with omalizumab during clinic visits; treatment response was rated as excellent, good, and partial based on a modified physician's Global Evaluation of Treatment Effectiveness (mGETE) scale of emergency room visits (ERV), hospitalization, use of oral corticosteroids, inhaled corticosteroid (ICS)/long-acting ß-agonist (LABA) dose, and short-acting ß-agonist rescue. The following tests were done: forced expiratory volume in 1 s (FEV1) and the asthma control test (ACT). Measurements were performed 1 month before therapy and at 16 weeks, 1 year, and 4 years of treatment. Statistical analyses were done using the Wilcoxon signed-rank test, Spearman rank correlation, and McNemar χ2 test. RESULTS: The dropout rate was 15 (18.5%): 8 nonresponders (10.0%); 2 patients died (2.5%), and 5 were lost to follow-up (6.25%). Treatment response was excellent in 35 (53.8%); good in 23 (35.4%), and partial in 7 patients (10.8%). The number of excellent responders increased from 35 (53.8%) at 16 weeks to 48 (73.8%) at the 4-year follow-up. The number of patients who did not require ERV improved from 0 to 59 (90.8%), and the lowest rate of hospitalization was 1 in year 4 (p < 0.001); patients who did not require courses of oral corticosteroids improved from 0 to 54 (83%). ICS/LABA dose significantly reduced from 65 (100%) to 25 (38.5%) after 4 years of treatment (p < 0.001); ACT scores significantly increased from 15 ± 3 at baseline to 23 ± 3 (p < 0.001) and FEV1 level from 55.6 ± 10.6 to 76.63 ± 10.34 at year 4. CONCLUSION: In this study, omalizumab therapy resulted in better asthma control, and was effective and well tolerated as an add-on therapy for patients with moderate-to-severe asthma.

Evaluation of the coronary circulation and calcification in children on regular hemodialysis.

BACKGROUND: The objective of this study was to evaluate the coronary circulation and calcification in children with end-stage renal disease (ESRD) on hemodialysis. METHODS: A total of 50 children with ESRD and 50 healthy controls were enrolled in the study. Cardiac functions and coronary blood flow were evaluated with conventional and tissue Doppler echocardiography. Coronary artery calcification (CAC) was evaluated using high-resolution multidetector computed tomography (CT). RESULTS: The hyperemic coronary flow volume (CFV) and coronary flow reserve were significantly lower in the patient group than in the controls, while there was no significant difference in the baseline CFV between the two groups. Hypertension was present in 60% and CAC was observed in 20% of the children in the patient group. CAC was present in 30% of the children in the hypertensive subgroup. The left ventricle myocardial performance index (LV MPI), CAC score, duration of hypertension and level of diastolic blood pressure were independent predictors of the coronary blood flow, and LV MPI, serum parathyroid hormone, duration of dialysis and E'/A' mitral valve were independent predictors of coronary calcification. CONCLUSION: High diastolic blood pressure, long duration of hypertension, high LV MPI and increased CAC scores are independent risk factors for impaired coronary blood flow in children with ESRD.

Beneficial Effects of Omega-3 Supplement to the Enteral Feeding in Children With Mild to Moderate Sepsis.

OBJECTIVE: The objective was to investigate the benefits of supplementing enteral feeding with omega-3 fatty acids in children with mild to moderate sepsis and its effects on acute-phase reactants and interleukin 6 (IL-6) level. METHODS: The study was a prospective randomized, double-blind, placebo-controlled study from January 2012 to June 2014, which included 2 groups of children with mild to moderate sepsis tolerating enteral feeding. Group A included 60 children supplemented with omega-3 fatty acids, whereas group B included 60 children who received enteral feeding without omega-3 supplementation. Both groups had complete blood pictures, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum albumin, and IL-6 before and after 7 days from supplementation. RESULTS: There was a significant improvement in hemoglobin percentage ( P < .0001), total white blood cell (WBC) count ( P < .0001), and platelet count ( P < .0001) and significant decrease in CRP ( P < .0001), ESR ( P < .0001), IL-6 ( P < .0001), and albumin level ( P < .001) in the supplemented group than the nonsupplemented group. The supplemented group also had a significantly shorter duration of stay in pediatric intensive care unit (PICU; P < .01) and decreased death rate than the nonsupplemented group. CONCLUSION: Children with mild to moderate sepsis showed significant improvement in inflammatory markers and had shorter PICU admission when enteral feeding was supplemented with omega-3 essential fatty acids.

The Role of Nitric Oxide from Neurological Disease to Cancer.

Until the beginning of the 1980s, nitric oxide (NO) was just a toxic molecule of a lengthy list of environmental pollutants such as cigarette smoke and smog. In fact, NO had a very bad reputation of being destroyer of ozone, suspected carcinogen and precursor of acid rain. However, by the early 1990s it was well recognized by the medical research community. Over the last two decades, the picture has been totally changed. Diverse lines of evidence have converged to show that this sometime poison is a fundamental player in the everyday business of the human body. NO activity was probed in the brain, arteries, immune system, liver, pancreas, uterus, peripheral nerves, lungs, and almost every system in the human body. NO is a major player in the cardiovascular system as it is involved in regulating blood pressure. In the CNS, it is involved in memory formation and the regulation of cerebral blood flow to ensure adequate supply of blood to the brain. Because NO is involved in many pathways, it has a role in several diseases related to modern life as hypertension, coronary heart diseases, Alzheimer's Disease, stroke and cancer. This chapter focuses on the discussion of the role of NO in neurological diseases and cancer and how can this Janus-faced molecule play a role in the pathology and personalized treatment of these diseases.

Oxidative stress and cardiac dysfunction in children with chronic renal failure on regular hemodialysis.

OBJECTIVE: The objective of this study was to evaluate cardiac function in children with end-stage renal disease (ESRD) on regular hemodialysis using speckle tracking echocardiography (STE) and correlate results with plasma glutathione level as a marker of oxidative stress. METHODS: The study involved 30 children with ESRD and 30 healthy controls. The plasma glutathione and C-reactive protein (CRP) levels were measured, and cardiac function was evaluated using conventional echocardiography and STE. RESULTS: Plasma glutathione levels were significantly lower and CRP significantly higher in patients than in controls. Children with ESRD had significant systolic and diastolic cardiac dysfunctions detected by STE compared with controls. Conventional echocardiography failed to detect these dysfunctions. There was significant increase in left-ventricular relative wall thickness (LV-RWT) in patients, especially those with hypertension, compared with the control group. There was also significant impairment of LV and right-ventricular (RV) global longitudinal strain (GLS) and torsion; however, LV-GLS was significantly better in hypertensive than in normotensive patients. The degree of impairment in GLS and cardiac torsion negatively correlated with plasma glutathione levels. CONCLUSION: Significant oxidative stress was present in children with ESRD and was correlated with the degree of cardiac dysfunction detected early using the new cardiac imaging modality, STE.

Primary Repair of Iatrogenic Medial Collateral Ligament Injury During TKA: A Modified Technique.

Intraoperative injury to the medial collateral ligament (MCL) is a rare but important complication of total knee arthroplasty (TKA). While described treatment methods are mainly primary repair and revision with a more constrained implant, a few studies have investigated the outcomes of primary repair without constrained implants. A retrospective study was performed to evaluate the prevalence of iatrogenic injury to the MCL during primary TKA and determine the clinical outcomes of MCL repair augmented with synthetic material without the use of a constrained device. The incidence of intraoperative tear of the MCL was 0.43% (15/3432). No patient demonstrated instability during the follow-up period. Primary repair of iatrogenic MCL injury without the use of constrained implants appears to be a potential alternative that warrants further investigation.

Holmium:YAG laser ureteroscopic lithotripsy for ureteric calculi in children: predictive factors for complications and success.

OBJECTIVES: To evaluate the impact of age, stone size, location, radiolucency, extraction of stone fragments, size of ureteroscope and presence and degree of hydronephrosis on the efficacy and safety of holmium:YAG (Ho:YAG) laser lithotripsy in the ureteroscopic treatment of ureteral stones in children. METHODS: Between October 2011 and May 2013, a total of 104 patients were managed using semirigid Ho:YAG ureterolithotripsy. Patient age, stone size and site, radiolucency, use of extraction devices, degree of hydronephrosis and size of ureteroscope were compared for operative time, success and complications. RESULTS: In all, 128 URS were done with a mean age of 4.7 years. The mean stones size was 11 mm. Success rate was 81.25 %. Causes of failure were 12.5 % access failure, 1.5 % extravasation and 4.7 % stone migration. Overall complications were 23.4 %. Failure of dilatation and extravasation were detected only in children <2 years old. Extravasation was significantly higher in smaller ureters and cases with stone size >15 mm. Stone migration was significantly higher in upper ureteric stones. CONCLUSIONS: Failure and complications rates in Ho:YAG ureterolithotripsy were significantly affected by younger age (<2 years), upper ureteric stones and smaller ureters but were not related to stone radiolucency or degree of hydronephrosis. Larger stones (>15 mm) were associated with increased complications. After multivariate analysis, the age of the patients remained significant predictor for failure of dilatation and stone migration, while size of the ureter was the only significant predicting factor for failure.

Association between interleukin-6-174G/C gene polymorphism and asthma severity: exploring the role of total serum IgE, blood eosinophils, and FeNO as markers of type 2 inflammation.

BACKGROUND: While a connection has been established between serum interleukin-6 (IL-6) levels and the IL-6 gene (- 174G/C) polymorphism in allergic diseases such as asthma, its specific association with severe asthma remains unexplored. This study examined the relationship between the IL-6 (- 174G/C) gene polymorphism and mild and severe asthma, focusing on its influence on type 2 inflammation. METHODS: Our study comprised 98 patients with mild asthma and 116 with severe asthma. Additionally, we recruited 121 healthy participants to serve as controls for comparative analyses. The IL-6 gene (- 174G/C) polymorphism was assessed utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In our study, the risk of mild asthma exhibited a significant fourfold increase in individuals with the GG genotype pattern compared to healthy controls, yielding an odds ratio (OR) of 4.4 (p < 0.001). Conversely, we found no significant correlation between the IL-6 - 174G/C gene polymorphism and severe asthma when compared to the healthy control group. However, a noteworthy pattern emerged when we compared subgroups of mild and severe asthma. The risk of severe asthma increased fivefold in individuals with the GC polymorphism pattern, with an OR of 4.99 (p < 0.001), while the likelihood of mild asthma showed a similar fourfold increase with the GG polymorphism pattern, OR = 4.4 (p < 0.001). Consequently, we observed a significantly higher frequency of the C allele in patients with severe asthma, whereas the G allele was more prevalent in individuals with mild asthma (p = 0.05). Additionally, the correlation between markers of type 2 inflammation and the dominant model of the IL-6 gene -174G/C polymorphism (CC + CG vs GG) revealed a significant increase in total serum immunoglobulin E (IgE), Blood Eosinophil Counts (BEC), and Fractional Exhaled Nitric Oxide (FeNO) levels in asthmatic patients with the CC + CG gene pattern compared to those with GG, with p-values of 0.04, 0.03, and 0.04, respectively. Furthermore, after adjusting for other risk factors, the likelihood of developing severe asthma increased from fourfold to eightfold, with an OR of 8.12 (p = 0.01) with (CC + CG) gene pattern. Other predictors for severe asthma included older age and childhood-onset disease (OR = 1.13 and 19.19, p < 0.001). Allergic rhinitis (AR) and nasal polyps (NP) also demonstrated a substantial association with an increased risk of severe asthma, with odds ratios of 5 and 32.29 (p = 0.01 and < 0.001), respectively. Additionally, elevated Body Mass Index (BMI), BEC, and FeNO were linked to severe asthma, with ORs of 1.11, 1.00, and 1.04, respectively (p = 0.04, 0.05, and 0.001). CONCLUSION: This study illuminated the intricate relationship between the IL-6 gene polymorphism, type 2 inflammation markers, and diverse risk factors in shaping asthma severity. As a significant association between the GG polymorphism of the IL-6 gene (- 174G/C) and mild asthma was found, while possessing at least one C allele, whether in a homozygous (CC) or heterozygous (CG) combination, independently predicts the likelihood of severe asthma.

Infective endocarditis presentations during the COVID-19 pandemic: have they paid an untold toll?

Background: COVID-19 caused restrictions and re-allocation of medical resources among all healthcare services. During the peak of the pandemic, several unrelated-yet critical-conditions had silently taken their toll. Infective endocarditis (IE), owing to its non-specific clinical presentation, may have been largely mislabeled as COVID-19 in a number of cases. Results: This retrospective observational study reviewed all IE presentations at an IE unit in a university hospital during the peak of COVID-19. Patient characteristics, courses, and outcomes were compared with historical controls from our IE database published before the COVID era. We identified 30 IE cases [Group A] during the COVID-19 peak in our region (June 2021 to June 2022), with a 25% decrease compared to the usual annual rate. This is in contrast to the expected surge during the pandemic. Compared with group B (398 published IE cases from our database), group A had significantly longer symptoms-to-presentation intervals (60 [31-92] vs. 28 [14-72] days, p = 0.01). Male sex dominated both groups, but group A had significantly less pre-existing structural heart disease. Despite the more liberal use of empirical antibiotics in the COVID-era, group-A had lower rates of culture-negative IE. Compared to group B, group A demonstrated a better response to medical therapy, fewer arterial embolizations, fewer indications for surgery, and fewer overall complications, except for increased acute kidney injury. This can be explained by the abundant use of non-steroidal anti-inflammatory drugs. The data analysis strongly suggests that there might have been a natural selection or selection bias of IE patients with favorable profiles to survive the pandemic to the appropriate diagnosis. Conclusions: The diagnosis of IE and commencing the appropriate workup were significantly undermined during the COVID-19 pandemic. The inexplicable decline in IE referral rate and the favorable outcomes witnessed during the pandemic strongly suggest a referral bias and natural selection of those who survived the pandemic to the appropriate IE diagnosis.