Symptomatic Treatment Research Articles

Chapter 14: Post surgical follow-up of primary hyperparathyroidism.

Primary hyperparathyroidism is treated surgically. Postoperatively, close monitoring of blood calcium levels is necessary to detect any hypocalcemia. Postoperative PTH assays can be performed within 24hours to identify patients who will not develop permanent hypoparathyroidism. Hypocalcemia may be caused by hypoparathyroidism (especially in the case of multi-glandular surgery or revision surgery) or by hungry bone syndrome. The latter should be suspected in case of major skeletal damage or severe preoperative vitamin D deficiency. It leads to severe hypocalcemia with normal or elevated PTH concentration, hypophosphatemia, hypomagnesemia, and low calciuria despite high doses of calcium and 1-25 OH vitamin D. Treatment of postoperative hypocalcemia depends on severity, symptoms and surgical procedure. In uni-glandular surgery, symptomatic treatment with calcium alone is recommended (0.5 to 1g/day). In multi-glandular involvement or repeat surgery, treatment with calcium (1 to 3g/day) is recommended if hypocalcemia is symptomatic or profound (<1.9mmol/L) (i.e. 76mg/L). If it is insufficient, the potential contribution of active vitamin D treatment should be assessed with an endocrinologist. If hypocalcemia is treated, patients should preferably be monitored by an endocrinologist (blood calcium level, calciuria and possibly phosphatemia and PTH). Under medical treatment of hypoparathyroidism, blood calcium levels should be monitored at least every 3 months for the first year, then at least twice a year.

Translational Approach using Advanced Therapy Medicinal Products for Huntington's Disease.

Current therapeutic approaches for Huntington's disease (HD) focus on symptomatic treatment. Therefore, the unavailability of efficient disease-modifying medicines is a significant challenge. Regarding the molecular etiology, targeting the mutant gene or advanced translational steps could be considered promising strategies. The evidence in gene therapy suggests various molecular techniques, including knocking down mHTT expression using antisense oligonucleotides and small interfering RNAs and gene editing with zinc finger proteins and CRISPR-Cas9-based techniques. Several post-transcriptional and post-translational modifications have also been proposed. However, the efficacy and long-term side effects of these modalities have yet to be verified. Currently, cell therapy can be employed in combination with conventional treatment and could be used for HD in which the structural and functional restoration of degenerated neurons can occur. Several animal models have been established recently to develop cell-based therapies using renewable cell sources such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stromal cells, and neural stem cells. These models face numerous challenges in translation into clinics. Nevertheless, investigations in Advanced Therapy Medicinal Products (ATMPs) open a promising window for HD research and their clinical application. In this study, the ATMPs entry pathway in HD management was highlighted, and their advantages and disadvantages were discussed.

Real-world dose intensity (DI) and time to adverse events (AEs) in a commercial database during first-line (1L) treatment of metastatic pancreatic adenocarcinoma (mPDAC) with FOLFIRINOX (FFX), FFX without 5FU bolus, and gemcitabine + nab-paclitaxel (GnP).

692 Background: Onset of severe AEs during 1L FFX and GnP treatment for mPDAC negatively impacts clinical outcomes, requiring supportive care and/or treatment adjustment. Occasionally they lead to discontinuation. The 5FU bolus may be omitted from FFX (FFXnb) to increase tolerability. We examined DI and time to key AEs (anemia, neutropenia, thrombocytopenia, diarrhea, fatigue, nausea/vomiting, and neuropathy) during 1L FFX, FFXnb, and GnP. Methods: This retrospective study utilized Optum Market Clarity claims + EHR linked data. Inclusion criteria were: adults diagnosed with mPDAC between 1/1/2015 and 5/31/2023; initiated 1L FFX, FFXnb, or GnP (index date) within -14 to +90 days; ≥6 pre- and ≥1 month post-index enrollment; ≥1 AE of interest in 1L. Follow-up was index to earliest of death, disenrollment, start of 2L, or last administration + 14 days. DI was defined as cumulative dose divided by follow-up in months. Grade 3/4 hematologic AEs (hAEs) were measured from lab values. Ungraded AEs were sourced from EHR notes and claims diagnoses. FFX was defined as including 5FU bolus + infusion in the 1st cycle; FFXnb as 5FU infusion only. Kaplan-Meier (KM) methods estimated time AE. Results: Median follow-up in months for patients (pts) with hAEs was: FFX 4.2; mFFX 3.6; GnP 3.1. Median DI (mg/m2/month) for FFX vs FFXnb pts with hAEs was: 5FU 4567 vs 4581; leucovorin 632 vs 398; oxaliplatin 119 vs 142; irinotecan 253 vs 251. For GnP, DI was: gemcitabine 2230; nab-paclitaxel 269. The table below presents sample size (N) and median (95% CI) time to AE. Median time to anemia was numerically 2–4 weeks shorter for GnP and FFXnb vs FFX. Time to neutropenia was 8–12 days less for FFXnb vs GnP and FFX. Time to thrombocytopenia was 7 weeks less for GnP vs FFX and FFXnb. Time to neuropathy was nearly 4 weeks shorter for FFXnb vs FFX and GnP. Conclusions: While neutropenia is higher risk for FFX vs GnP, prophylactic growth factor is standard during FFX, which may result in the similar onset time vs GnP. Early onset of severe thrombocytopenia differentiates the GnP sample. Oxaliplatin DI was higher for FFXnb vs FFX pts, and may be associated with earlier onset of anemia, neutropenia, diarrhea, and neuropathy. Research is merited on interactions between dosing, AE timing, and treatment discontinuation. Time to AE. Grade 3/4 hAEs FFX N FFXnb N GnP N FFX median days (95% CI) FFXnb median days(95% CI) GnP median days (95% CI) Anemia 47 25 97 64 (38–96) 36 (19–70) 47 (39–56) Neutropenia 75 53 112 35 (25–47) 23 (14–43) 31.5 (18–42) Thrombocytopenia 33 22 54 63 (35–79) 65.5 (32–94) 14 (13–34) Ungraded AEs Diarrhea 216 264 297 27.5 (22–36) 17.5 (14–27) 27 (21–36) Fatigue 211 267 418 34 (23–43) 27 (17–34) 27 (21–30) Nausea/vomiting 337 403 561 6 (3–8) 9 (7–14) 9 (7–12) Neuropathy 151 155 190 92 (70–112) 67 (48–79) 92 (80–111)

Chlorpheniramine maleate exerts an anti-keloid activity by regulation of IL-6/JAK1/STAT3 signaling pathway.

Keloids are abnormal scars formed due to fibroblast dysfunction and excessively deposited extracellular matrix (ECM). Despite the unclear process leading to the occurrence of keloids, several studies have demonstrated that histamine and its H1 receptor can effectively regulate fibroblast functions, contributing to keloid formation. Chlorpheniramine maleate (CPM) as a first-generation H1 antihistamine has been widely applied in symptomatic treatment of allergic conditions but its effects on keloids are unknown. This study holds the objective of exploring its effect on keloids. Cell Counting Kit-8 (CCK-8), apoptosis, cell cycle and migration assays were conducted to determine the effects of CPM on human keloid fibroblasts (KFs), with its therapeutic effect evaluated by constructing a keloid model in nude mice. RNA sequencing analysis, ELISA, western blotting and immunohistochemistry assisted in examining the anti-keloid mechanism of CPM. It was observed that CPM inhibited the proliferation and migration of KFs, promoted apoptosis of KFs, and blocked the G0/G1 phase of KFs. Moreover, local intralesional injection of CPM into nude mice keloid model significantly reduced keloid scars. According to RNA sequencing analysis, the gene expression of IL-6 and JAK-STAT signaling pathway were both negatively related in CPM group versus the control group. According to the in vivo and vitro experiment results, the anti-keloid activity of CPM was attributed to its inhibitory effect on the IL-6/JAK1/STAT3 signal pathway. In summary, CPM holds great potential for localized treatment of keloids.

Chest pain and coronary artery disease in cardiac amyloidosis: Prevalence, mechanisms, and clinical implications.

Amyloidosis is a systemic disease affecting multiple organs, and often presents with cardiac involvement, with 2 primary underlying pathologies: amyloid light chain- and transthyretin cardiac amyloidosis. Chest pain can occur in both types with variable clinical presentations. This narrative review describes the relationship between cardiac amyloidosis (CA) and chest pain. A PubMed search (June 03. 2024) identified 393 articles related to chest pain in CA. Twenty-eight studies, in English and with full text, were selected. Articles included were case reports, reviews, perfusion- and autopsy studies. In CA patients 10%-20% report chest pain as the initial symptom preceding the diagnosis, and the overall prevalence of chest pain is 38% of patients with CA and it is related to an increased risk of heart failure hospitalization. The mechanisms leading to chest pain in CA patients include increased left ventricular diastolic pressure, infiltration of amyloid fibrils inside and around coronary arteries, and amyloid compression of the microvasculature. The mechanisms commonly lead to elevations of plasma troponin levels, which are higher in amyloid patients with chest pain compared to amyloid patients without chest pain. Symptomatic treatment of chest pain can be challenging due to the low tolerability of medical therapy and poor outcomes of coronary interventions in alleviating the pain and with a higher rate of complications. Our review underscores the importance of recognizing chest pain as a CA symptom, particularly in the elderly. Persistent troponin elevation without coronary artery disease could indicate CA. Screening-based and longitudinal studies are crucial for understanding the relationship between chest pain and CA. Acknowledging the significance of chest pain in CA may facilitate early intervention and improve patient outcomes.

Development of hot melt extruded Polycaprolactone (PCL) matrices for an oral ultra-long-lasting delivery of Galantamine for Alzheimer’s disease therapy

Galantamine Hydrobromide (GAL) is a tertiary alkaloid, acting as a competitive and reversible cholinesterase inhibitor. It is indicated for the symptomatic treatment of patients from mild to moderate dementia level of the Alzheimer’s disease (AD) type. For treatment of mild to moderate AD, GAL is generally combined with other drugs. The purpose of this work was development and characterization of hot melt extruded (HME) matrices based on polycaprolactone (PCL) for GAL oral ultra-long-lasting delivery. PCL is biodegradable polymer, biocompatibility, water-insoluble and excellent for HME process. From HME drug and polymer mixtures arms from 1 % up to 50 wt-% of GAL were obtained. The raw materials and the as-obtained HME arms were characterized by particle size distribution (PSD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), wide angle x-ray scattering (WAXS) and dissolution test. Our findings showed that GAL possesses crystalline form I polymorphic, it is thermodynamically stable, and remains their particle and crystalline form even after HME process. Crystallization temperature of PCL increases with GAL content, indicating strong heterogeneous nucleating effect of drug on polymer crystallization process. SEM morphological analysis indicates continuous polymeric phase on surface. However, higher amounts of GAL (50/50 wt-%) presented clusters and heterogeneity, especially in extruded cross-section. It may have influenced the drug release property, decreasing the sustained release ability, due to the transport of medium molecules through the bulk extrudates by GAL soluble clusters. The diffractograms (WAXS) showed patterns peaks of GAL and PCL, indicating that GAL remains its crystalline structure and PCL recrystallized. In the dissolution test, PCL/GAL 80/20 and 90/10 achieved 100% with over seven days and profiles that can be tuned by varying GAL concentration. Finally, we demonstrate the feasibility of using HME process based on the mixture of PCL and GAL as proposals for oral therapies for conditions of AD. This is the first report showing PCL-GAL polymer matrices that achieves several-days drug release.

2023 epidemic dengue fever outbreak: the experience of a pediatric hospital in the City of Buenos Aires.

Introduction. Dengue is a viral infection that may be asymptomatic or include severe manifestations. This study aims to describe the characteristics of a pediatric population during the epidemic outbreak in 2023. Population and methods. This cross-sectional study included patients with probable or confirmed dengue fever who were seen from March 13, 2023, to May 19, 2023, in a pediatric hospital in the Autonomous City of Buenos Aires. Results. A total of 112 patients were included. The median age was 12 years; 58% were male. Seventy-six percent of them came from the City of Buenos Aires. Twenty-five percent had cohabitants with symptoms compatible with a suspected case. The most frequent clinical manifestations were fever, headache, retro-ocular pain, myalgia, and arthralgia. The most frequent laboratory alterations were leukopenia (65%) and elevated transaminases (60%). Twenty-one percent (24/112) presented alarm signs and required hospitalization. Leukopenia, plateletopenia, and elevated transaminases were associated with the presence of alarm signs. RT-PCR was detected in fifty-three patients; serotype 2 was the most frequent. Twenty-one patients had positive NS1 tests, 18 patients had positive IgM, and 20 patients with clinical and epidemiological links were assumed to be probable dengue cases. There were no cases of severe dengue. Conclusion. Early clinical suspicion and recognition of laboratory parameters associated with alarm signs are essential for an adequate approach to the disease and early supportive treatment during dengue infection.

Antiviral properties of essential oil mixture: Modulation of E7 and E2 protein pathways in human papillomavirus (HPV) infection.

Clove is used in Indian and Chinese traditional medicine for viral diseases. Palmarosa essential oils have been traditionally used in India and Southeast Asia since ancient times and have made considerable use of them. In New Caledonia, niaouli oil is used in aromatherapy and pharmaceutical formulations to treat pain and viral diseases. Since ancient times, the South Pacific region has used tamanu oil as a traditional medicine to treat a wide range of skin conditions. This study investigates the antiviral properties of essential oils (EOs) from Eugenia aromaticum (clove oil, CL-R030424005 (CL)), Cymbopogon martinii (palmarosa oil, PA-R040923008 (PA)), Melaleuca viridiflora (niaouli oil, NI-R290124038 (NI)), and Calophyllum inophyllum (tamanu oil, TA-F140224029 (TA)), and their mixture against human papillomavirus (HPV) infection. A D-optimal mixture design is used to determine the most effective EO combinations and evaluate their antiviral efficacy through IC50 values. The EOs were tested for their ability to inhibit HPV-related oncogenes (L1, L2, E1, E2, E6, and E7) in HPV-infected cells with ELISA, qPCR, and Western blot analyses. The optimal mixture (31.5% CL, 31.5% PA, and 37% NI) demonstrated significant antiviral activity, reducing viral replication and protein expression in HPV-infected cells. Ex-vivo permeation studies showed higher permeation rates in healthy tissues compared to infected ones, indicating the oils' potential in targeted drug delivery. Additionally, cytotoxicity assessments confirmed the safety of the EOs at effective concentrations in HPVCs, DoTc2, and HEKa cells. Molecular docking studies further elucidated the interactions between EO components and HPV proteins, supporting their antiviral mechanisms. These findings suggest that EOs, particularly in optimized combinations, offer a promising natural supportive treatment for managing HPV infections, warranting further in vivo animal tests and clinical trials.

Anatomy-wise lung ventilation imaging for precise functional lung avoidance radiation therapy.

&#xD;This study aimed to propose a method for obtaining anatomy-wise lung ventilation image (VIaw) that enables functional assessment of lung parenchyma and tumor-blocked pulmonary segments. The VIaw was used to define multiple functional volumes of the lung and thereby support radiation treatment planning.&#xD;Approach:&#xD;A super-voxel-based method was employed for functional assessment of lung parenchyma to generate VIsvd. In the VIsvd of the 11 patients with tumor blockage of the airway, the functional value in tumor-blocked segments was set to 0 to generate the VIaw. The lung was divided into regions of high functional volume (HFV), unrecoverable low functional volume, and recoverable low functional volume (rLFV, the region in the tumor-blocked segment with a high function value based on the VIsvd) to design three intensity-modulated photon plans for five patients. These plans were an anatomical-lung-guided plan (aPlan), a functional-lung-guided plan (fPlan), and a recoverable functional-lung-guided plan (rfPlan) where the latter protected both HFV and rLFV.&#xD;Main results:&#xD;The low functional volume in the reference ventilation images and the tumor-blocked segments had a high overlap similarity coefficient value of 0.90 ± 0.07. The mean Spearman correlation between the VIaw and reference ventilation images was 0.72 ± 0.05 for the patient with tumor blockage of the airway. The V20 and mean dose of rLFV in rfPlan were lower than those in aPlan by 12.1% ± 8.4% and 13.0% ± 6.4%, respectively, and lower than those in fPlan by 14.9% ± 9.8% and 15.9% ± 6.5%, respectively.&#xD;Significance:&#xD;The VIaw can reach a moderate-strong correlation with reference ventilation images and thus can identify rLFV to support treatment planning to preserve lung function.&#xD.

Community acquired gastroenteritis

Gastrointestinal infections are widespread and a major cause of global mortality, mainly affecting young children and the elderly. In Germany, each resident typically experiences one episode yearly. After COVID-19 pandemic, gastrointestinal infection rates have significantly increased again. Acute gastroenteritis typically presents with sudden stool changes, vomiting, and fever. In Germany, common pathogens include norovirus, rotavirus, Campylobacter spp., and Salmonella spp. New German guidelines on infectious gastroenteritis (published 2023) reflect recent studies and international treatment standards. The diagnosis of acute gastroenteritis should be based on clinical presentation and a thorough medical history, with stool testing reserved for severe cases or suspected outbreaks. Symptomatic treatment and rehydration of the patient are usually sufficient. Antibiotic treatment is generally not recommended except in severe cases, risk situations or the detection of specific pathogens.

P-114. Efficacy of Vaginal-Spraying Bacillus Spore Probiotics in Supportive Treatment of Sexual Transmission Infections: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Abstract Background Sexually Transmitted Infections (STIs) are common gynecological infections worldwide. While antibiotics drugs are typically utilized to treat STIs caused by pathogenic bacteria, the over use of antibiotics may lead to side effects and the emergence of drug resistance. Hence, vaginal-spraying probiotics could offer a safe and effective symptomatic treatment for STIs, presenting a promising alternative to standard therapy. The Effect of Vaginal-Spraying Bacillus Spore Probiotics (LiveSpo X-SECRET) in Reducing Gardenella vaginlis Concentrations in Vaginal Swab. Methods We conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy of vaginal-spraying probiotics containing spores of Bacillus subtilis, B. clausii, and B. coagulans (&amp;gt; 1 billion/mL) in supporting the treatment of vaginal infections. The study comprised 100 eligible patients visiting Bac Ninh Center for Disease Control, randomly divided into 2 groups (n = 50/group). The standard treatment regimen lasted 7 days and was maintained for 28 days. The Control group received NaCl 0.9% physiological saline in addition, while the X-Secret group was additionally treated with LiveSpo X-SECRET. This trial was registered at clinicaltrials.gov as NCT06165354. Results LiveSpo X-SECRET did not cause skin or vaginal mucosal irritation and exhibited supportive effects in significantly reducing typical symptoms of vaginal infection, indicated by a lower percentage of patients experiencing vaginal odor, vaginal itching, urinary pain, and abnormal vaginal discharge coloration in the X-Secret group observed at days 3, 7, 14, and 28, compared to the Control group. The clinical findings were supported by real-time PCR detection of STIs, indicating a reduction in pathogenic G. vaginalis concentration by approximately 11-260 folds and an increase in beneficial Lactobacillus sp. by around 102-103 folds, more effectively observed in vaginal swabs from the X-Secret group compared to the Control group on days 3, 7, 14, and 28. Additionally, 16S rRNA metagenome analysis data revealed that LiveSpo X-SECRET restored vaginal microbiota by increasing the density of Lactobacillus while reducing some harmful genera. Conclusion Vaginal-spraying Bacillus spore probiotics (LiveSpo X-SECRET) can be considered a simple and effective agent for supportive treatment of sexually transmitted infections. . Disclosures Huyen Thi Nguyen, MSc. in Biotechnology, LiveSpo Pharma Ltd.: Expert Testimony|LiveSpo Pharma Ltd.: Huyen Thi Nguyen receives a monthly salary from LiveSpo Pharma., and does not receive any additional compensation for her involvement in this study. Anh Hoa Nguyen, PhD. in Life Sciences, LiveSpo Pharma Ltd.: Board Member|LiveSpo Pharma Ltd.: Anh Hoa Nguyen receives a monthly salary from LiveSpo Pharma , and does not receive any additional compensation for his involvement in this study.|LiveSpo Pharma Ltd.: Ownership Interest

P-111. Promising Efficacy of Nasal-Spraying Bacillus Spore probiotics for Supportive Treatment of Pneumonia in Children with RSV and Bacterial Co-infections

Abstract Background : Respiratory syncytial virus (RSV) and bacterial co-infections are primary cause of pneumonia. Recently, nasal-spraying Bacillus spore probiotics (LiveSpo NAVAX containing ≥ 5 billion/5mL B. subtilis and B. clausii spores) have demonstrated its effectiveness in supporting the treatment of acute respiratory tract infections caused by RSV and Influenza virus1,2. Methods A randomized, double-blind, controlled clinical trial was conducted to evaluate the efficacy of LiveSpo NAVAX in the supportive treatment of severe pneumonia due to RSV and bacterial co-infections. A total of 120 eligible pediatric patients were randomly assigned to two groups: the Control group received 0.9% NaCl physiological saline, and the probiotic-intervention group (Navax group) received LiveSpo NAVAX three times a day. Results At day 3, the Navax group demonstrated significant reductions in both RSV and bacterial co-infection 15.7 and 40.8-fold greater than those observed in the control group. Notably, H. influenzae and S. pneumoniae were reduced by 22.8 and 17.2 folds, respectively. Additionally, the Navax group exhibited significant decreases in pro-inflammatory cytokines (IL-6, IL-8, TNF-α), with levels reduced by 1.4 - 3.6 folds, while also enhancing the immune system (IgA) by over 67.04%. Furthermore, the 16S rRNA metagenomic analysis revealed the restoration of nasal microbiota, with an increase in the density of beneficial genus such as Corynebacterium, Bacillus and a reduction in the density of harmful genus including Streptococcus, Haemophilus, and Moraxella. Conclusion Our data demonstrate that nasal-spray Bacillus spore probiotics supported the treatment of pneumonia in children by reducing RSV, co-infection bacterial loads, and pro-inflammatory cytokines. Disclosures All Authors: No reported disclosures

P-448. Contextual assessment and potential barriers and facilitators of a mobile health program to support treatment of tuberculosis and HIV in Kilimanjaro, Tanzania: opportunities for care integration

Abstract Background Despite increasing smartphone penetration globally, personalized mobile health (mHealth) care interventions remain largely untapped for people with tuberculosis (TB) in many settings. A smartphone platform adopted to support treatment of human immunodeficiency virus (HIV) in the US was adapted and piloted for HIV/TB care in a distinct urban population, with high usage and improved clinical outcomes. Systematic evaluation of potential contextual influences on mHealth implementation is needed to ensure appropriateness, feasibility, and acceptability of the intervention for HIV/TB care within Kilimanjaro.Table 1:Perspectives on existing HIV and TB care delivery experiences and integration of services Methods We conducted semi-structured in-depth interviews at Kilimanjaro Christian Medical Centre and Kibong’oto Hospital with patients (18 y/o+ with drug-susceptible/drug-resistant-TB, with/without HIV, &amp;gt; 1 month on treatment) and providers (e.g. physicians, nurses). Guides were designed using Bury’s Framework for Chronic Illness and the Consolidated Framework for Implementation Research (CFIR). Analysis was performed using a priori open coding/constant comparisons methodology. A preliminary codebook built deductively from frameworks was iterated with inductive codes based on emergent themes. Results To date, 12 patient and 12 provider interviews have been conducted; analysis is underway. Specific perspectives demonstrated opportunities for enhancement of HIV/TB care integration (Table 1). Preliminary analysis suggests feature phone access is more common among patients. Additional themes relate to perceptions of an external intervention source (CFIR domain: Intervention Characteristics), compatibility with current provider smartphone access/workload, existing directive nature of patient-provider relationships, and current level of system digitization at sites (workplace internet stability/data access) (Inner Setting). Conclusion Analysis to date reveals several prominent themes to consider for adaptation of the intervention: 1) daily life/experiences with TB/HIV 2) determinants of and 3) experiences with TB/HIV care 4) mobile phone ownership, usage 5) perceptions of the intervention within the context and to support 6) home urine testing for personalized dosing of TB medications. Disclosures Jacqueline Hodges, MD MPH, Gilead Sciences: Grant/Research Support

Un caso di encefalopatia posteriore reversibile a tre giorni dalla diagnosi di leucemia linfoblastica acuta B

Posterior reversible leukoencephalopathy syndrome (PRES) is a clinical radiographic syndrome of heterogeneous etiologies characterised by acute neurological symptoms of brain dysfunction with MRI abnormalities, primarily in posterior cerebral white and grey matter. In most cases, symptoms resolve without neurological consequences. The paper reports the case of a 13-year-old teenager who showed hypertension and altered consciousness with status epilepticus at the electroencephalographic (EEG) monitoring three days after Acute Lymphoblastic Leukaemia diagnosis. The only therapy she went through was prednisone. At the diagnosis of PRES hypertension is frequent but not invariable. The hypertensive crisis may precede the neurologic syndrome by 24 hours or longer. In the paediatric population seizures and/or status epilepticus are often the presenting manifestation. Neuroimaging is essential to the diagnosis of PRES; typical findings are bilateral areas of white matter oedema in the posterior cerebral hemispheres, particularly the parieto-occipital regions, but variations do occur. Treatment is a symptomatic and supportive therapy. In many cases, PRES seems to be fully reversible within a period from days to weeks, after removal of the inciting factor and control of the blood pressure. Radiologic improvement is slower than clinical recovery.

Blood culture isolates and antimicrobial sensitivities from 1621 critically ill neonatal foals (2005-2022).

Sepsis is a leading cause of morbidity and mortality in neonatal foals. Administration of appropriate antimicrobials and early aggressive supportive treatment is central to the efficacious treatment of neonatal sepsis and has proven to positively influence outcomes. The primary aim of our study was to evaluate microorganism results and antimicrobial sensitivities of neonatal foals with a positive blood culture submitted to our intensive care unit (ICU) during 2005-2022. The secondary aim was to compare the results to those of a similar previous study performed at the same ICU during 1999-2004. Retrospective analysis of bacterial blood culture results from neonatal foals ≤7 days of age admitted to Scone Equine Hospital between 2005 and 2022 was analysed. Samples were collected at admission. Antimicrobial sensitivity testing was assessed using the Kirby-Bauer disc diffusion method. Susceptibility results from the two study periods were compared using Fisher's exact tests. Statistical significance was achieved at P value <0.05. From 1621 blood cultures submitted, 380 returned a positive result (380/1621; 23.4%). A total of 402 bacterial isolates were recovered: 55.5% Gram-positive isolates (223/402), 42.6% Gram-negative isolates (171/402) and 1.7% anaerobic isolates (7/409). A significant increase in Gram-positive isolates between time periods was observed (P = 0.002). Gram-negative isolates had significant increases of resistance in seven out of nine antimicrobials tested. This study provides Australian veterinarians with information on common bacterial pathogens in critically ill neonatal foals to assist with making informed empirical antimicrobial choices to optimise treatment efficacy. Increases in bacterial resistance to commonly administered antimicrobials were observed; therefore, culture and sensitivity testing should guide antimicrobial choices. Judicious use of antimicrobials in equine practice is imperative.

New and Emerging Biological Therapies for Myasthenia Gravis: A Focussed Review for Clinical Decision-Making.

Myasthenia gravis (MG) is a rare autoimmune disease characterised by exertion-induced muscle weakness that can lead to potentially life-threatening myasthenic crises. Detectable antibodies are directed against specific postsynaptic structures of the neuromuscular junction. MG is a chronic condition that can be improved through therapies, but to date, not cured. Standard treatment has been unchanged for decades and includes symptomatic treatment with acetylcholine-esterase inhibitors and disease-modifying treatment with steroids, steroid-sparing immunosuppressants and thymectomy. Overall, a relevant proportion of patients does not achieve a satisfactory clinical improvement under standard treatment. Additionally, long-term therapy with steroids can cause significant side effects and latency to clinical improvement with standard steroid-sparing immunosuppressants and after thymectomy can take months to years. In recent years, treatment of MG has changed fundamentally due to improved evidence from phase 3 trials and the regulatory approval of complement inhibitors and FcRn inhibitors as add-on treatment options. This provides new optimism for substantially more patients reaching minimal manifestation status and has led to a shift in treatment strategy with more targeted therapies being employed early in the course of the disease, especially in patients with high disease activity. In this focussed review, we provide an overview of the diagnosis, classification and standard treatment of MG, followed by data from randomised controlled trials on the modern drugs already available for therapy and those still in the final stages of clinical development. In the second part, we provide an overview of real-world data for already approved therapies and outline how the availability of new biologicals is changing both clinical decision-making and patient journey.

Co-presentation of diabetic ketoacidosis and hepatitis an infection with anasarca: a case report

Diabetic ketoacidosis is the common initial presentation of Type 1 Diabetes Mellitus in paediatric practice. Hepatitis A infection is a common cause of jaundice in children with varied constitutional symptoms. However, co-presentation of diabetic ketoacidosis and hepatitis A infection with anasarca is rare. One four-year-ten-month-old male child presented to the emergency department of our hospital with diabetic ketoacidosis with new-onset Type 1 diabetes mellitus. At the time of presentation, the blood sugar level was in the diabetic range, 677 mg% laboratory value and was suggestive of diabetes mellitus. The HbA1c level was 14.47% at that time; however, there was no history of the classical triad of polyuria, polydipsia and polyphagia in the child. The child presented with mild acidosis (pH 7.3) and responded to the Milwaukee regimen of DKA management. During the course of the management, the child developed clinical jaundice on the 5th day of hospital admission and was investigated and diagnosed as having viral hepatitis A. On the 7th day of illness, the child developed anasarca in the form of moderate pleural effusion and gross ascites, leading to respiratory distress along with pedal edema and scrotal edema. The anasarca responded to symptomatic treatment and the clinical improvement of Hepatitis A occurred after 15 days. The stressful event of brewing hepatitis A, precipitating DKA in a relatively asymptomatic child of type 1 diabetes mellitus, is more likely in our case. The chance association of both the conditions in an underweight child with a history of 3rd degree consanguinity is noted in our child. The child also developed anasarca, which is uncommon in viral hepatitis A or diabetic ketoacidosis alone.

Meckel's Diverticulum-Induced Intussusception Coinciding with Diabetes Mellitus in a Young Adult Male

Introduction: Intussusception in adults, especially when caused by Meckel's Diverticulum, is a rare occurrence, often presenting with nonspecific symptoms such as abdominal pain and nausea, making it challenging to diagnose. When concurrent with conditions like diabetes mellitus, the situation need particular care. Case Illustration: A 27-year-old male with a medical history of diabetes presented with severe right abdominal pain, nausea, and a reduced appetite. Initial symptomatic treatment did not alleviate the condition. Subsequent CT scans revealed an ileo-ileal intussusception triggered by Meckel's Diverticulum and partial high obstruction ileus, leading to surgical intervention. Discussion: Ileo-ileal resection (end to end anastomosis) and adhesiolysis surgery were successfully performed, followed by vigilant postoperative monitoring for complications, effective pain management, maintenance of drain patency, and careful glucose level monitoring. The patient's significant postoperative improvement underscores the importance of early diagnosis and timely surgical intervention in managing Meckel's Diverticulum-induced intussusception in adults. Conclusion: The clinical course also highlighted the importance of tailoring postoperative care considering the patient's comorbidities, in this case, diabetes mellitus. This case served as a reminder for clinicians to consider Meckel's Diverticulum as a potential cause of intussusception in adults presenting with abdominal pain.

Alleviating symptoms of paediatric acute rhinosinusitis and acute otitis media with otorrhea using nasal-spraying Bacillus probiotics: a randomized controlled trial

Acute rhinosinusitis (ARS) in children may be accompanied by acute otitis media (AOM) which is often associated with bacterial co-infections. These conditions are among the primary reasons that children visit hospitals and require antibiotic treatment. This study evaluated the efficacy of the nasal-spraying probiotics (LiveSpo Navax containing 5 billion Bacillus subtilis and B. clausii spores/5 mL) as a supportive treatment for dual ARS and AOM with otorrhea in a randomized, single-blind, controlled clinical trial. Eighty-two patients (41 per group), aged 1 month to 12 years, received standard care along with nasal spraying of either physiological saline (Control group) or LiveSpo Navax (Navax group), administered three times daily over a 7-day follow-up period. A total of sixty-one patients (30–31 per group) completed the trial. The Navax group experienced 68.00% and 96.77% reductions in nasal congestion (by day 3) and rhinorrhea (by day 7), respectively, which were 2.04 and 1.94-fold higher than the Control group, with odds ratios (OR) of 4.31 and 30.00 (p < 0.05). Endoscopic results indicated 8% and 11% higher reductions in nasal mucopurulent discharge and tympanic membrane hyperemia in the Navax group compared to the Control group. By day 3, compared to day 0, the Navax group exhibited > 1200-fold reduction in Streptococcus pneumoniae and ≥ 4-fold reduction in Haemophilus influenzae concentrations (p < 0.05) in both nasopharyngeal and middle ear fluid samples, whereas the Control group showed no significant reductions. Navax treatment reduced IL-6 by 1.35- to 1.74-fold and TNF-α by 1.17- to 1.45-fold, more effectively than the Control group (p < 0.05). These results suggest that nasal-spray Bacillus spore probiotics, with their ability to reduce bacterial load and modulate immune responses, provide a cost-effective and safe solution for alleviating symptoms of both ARS and AOM in children.Trial registration: ClinicalTrials.gov, Identifier NCT05804123 on April 7, 2023.

Use of metformin in treatment of dengue fever

Dear Editor, Dengue Fever is the fastest spreading mosquito-borne viral disease globally, affecting greater than 100 million humans annually. Dengue also causes 20 to 25,000 deaths, primarily in children, and is found in more than 100 countries. Although most cases are asymptomatic, severe illness and death may occur. (1) According to the WHO, between 1st January to 27th September 2022, the National Institute of Health-Islamabad reported 25,932 confirmed dengue cases and 62 deaths nationwide (2). 74% of these cases were reported during September alone. Of these, 32% were from Sindh, 29% from Punjab (including the Islamabad Capital Territory), 25% from Khyber Pakhtunkhwa (5506), and 14% from Balochistan (2). The current treatment for dengue fever doesn't involve direct medication. Instead, the focus is on symptomatic treatment. Initial steps focus on bed rest and increased fluid intake to combat dehydration caused by vomiting. In severe cases, hospitalization for supportive care becomes necessary. Patients are monitored for dehydration and electrolyte balance, platelet counts, and blood pressure, with interventions such as transfusions if needed (3). New and improved treatments for dengue are being explored worldwide. One of these emerging treatments is the efficacy of metformin in dengue treatment. A study published in 2018 showed that diabetic dengue patients who were metformin users were 33-40% less likely to develop severe dengue- according to WHO 2009 dengue criteria- than those who were not. (4) From the metformin users 28.2% progressed to severe dengue whereas from the non-metformin users 42.4% progressed to severe dengue. The same study showed that metformin users had a significantly lower instance of severe bleeding than non-users. In obese patients the enzyme Adenosine Monophosphate (AMP) – Activated protein kinase (AMPK) is down regulated. Its down regulation results in the inhibition of lipid catabolism and increased de novo lipid synthesis, which are favourable conditions for viral replication and survival within host cells (5). The hypoglycaemic agent metformin –dymethybiguanide- controls glucose metabolism via activation of AMPK. Hence obese patients with dengue could benefit from it. Bearing in mind the rising cases of dengue in Pakistan, we suggest that the possibility of an improved treatment with metformin, especially in obese patients, should be explored in the country. Metformin is cheap (locally priced at 35 rupees, brand name Glucophage), easy to administer and does not have any major side effects. ---Continue