Symptomatic Treatment Research Articles

[Sequence variants of unknown significance in small fiber neuropathy : Characterization of a heterogeneous patient population].

In almost half of patients suffering from small fiber neuropathies (SFN), the etiology remains elusive. For these patients with "idiopathic SFN", symptomatic analgesic therapy is the only option. Reports on apotential genetic background of neuropathic pain syndromes are increasing and particularly in SFN patients, several genetic variants were found mainly located in genes encoding voltage-gated sodium channels. Although up to 30% of SFN patients show genetic alterations, most of these remain of "unknown pathogenic significance" and little is known about "genetic SFN". The study aimed to determine clinical characteristics of SFN patients carrying arare genetic variant of unknown significance in pain-associated genes. From 2015 to 2020, 66patients with primarily idiopathic SFN were examined and rare gene variants of unknown significance detected in 13/66 (20%) of these. Adetailed medical history with focus on pain was recorded and patients filled in standardized questionnaires to assess physical and emotional burden due to pain. The authors found 13/66 (20%) patients with rare variants of unknown significance located in pain-associated genes who reported pain refractory to analgesic treatment, ahigher number of external factors influencing clinical symptoms, and ahigher level of physical impairment and emotional stress due to pain compared with patients without such genetic variants. Early genetic assessment is recommended to optimize the management of patients with potentially hereditary SFN. Early access to rehabilitation and mental support as well as aconsequent elimination of external triggering factors should be granted.

Relationship Between Coronary Artery Revascularization and Postoperative Delirium: Progress and Perspectives.

Brain dysfunction resulting from damage to the heart-brain link leads to a decline in cognitive function. This, in turn, gives rise to the clinical symptom of perioperative delirium in patients undergoing coronary artery revascularization. Those affected are provided symptomatic treatment, but many do not recover fully. Thus, medium- and long-term mortality and adverse event rates remain relatively high in patients with perioperative delirium. Despite the relatively high incidence of perioperative delirium in patients undergoing coronary artery revascularization, it has not been systematically investigated. Inflammation, vascular damage, neuronal damage, and embolism are all involved in the injury process. Here, we discuss the incidence rate, pathological mechanisms, and prognosis of delirium after coronary artery revascularization. We also discuss in detail the risk factors for delirium after coronary artery revascularization, such as anxiety, depression, mode of operation, and drug use. We hope that prevention, early diagnosis, assessment, and potential treatment can be achieved by cardiologists to improve patient prognosis.

Pharmaceutical equivalent 5-aminolevulinic acid fluorescence guided resection of central nervous system tumors: feasibility, safeness and cost-benefit considerations.

5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) has been an essential tool in the 'standard of care' of malignant gliomas. Over the last two decades, its indications have been extended to other neoplasms, such as metastases and meningiomas. However, its availability and cost-benefit still pose a challenge for widespread use. The present article reports a retrospective series of 707 cases of central nervous system (CNS) tumors submitted to FGR with pharmacological equivalent 5-ALA and discusses financial implications, feasibility and safeness. From December 2015 to February 2024, a retrospective single institution series of 707 cases of 5-ALA FGR were analyzed. Age, gender, 5-ALA dosage, intraoperative fluorescence finding, diagnosis and adverse effects were recorded. Financial impact in the surgical treatment cost were also reported. there was an additional cost estimated in $300 dollars for each case, increasing from 2,37 to 3,28% of the total hospitalization cost. There were 19 (2,69%) cases of asymptomatic photosensitive reaction and 2 (0,28%) cases of photosensitive reaction requiring symptomatic treatment. 1 (0,14%) patient had a cutaneous rash sustained for up to 10 days. No other complications related to the method were evident. In 3 (0,42%) cases of patients with intracranial hypertension, there was vomiting after administration. FGR with pharmacological equivalent 5-ALA can be considered safe and efficient and incorporates a small increase in hospital expenses. It constitutes a reliable solution in avoiding prohibitive costs worldwide, especially in countries where commercial 5-ALA is unavailable.

Abstract PO1-28-04: PILHLE-001: neoadjuvant pyrotinib combined with chemotherapy in HR-positive, HER2-low (IHC 2+/FISH-negative) early breast cancer

Abstract Background: Hormone receptor (HR)-positive/HER2-low (IHC 2+/FISH negative or IHC 1+) breast cancers (BCs) represent the largest proportion of breast carcinomas. However, its response to neoadjuvant chemotherapy or endocrine therapy is the lowest, with a residual cancer burden (RCB) 0/I rate around 15%. Previous studies have demonstrated that pyrotinib (P), a pan-HER tyrosine kinase inhibitor, exhibits excellent response in HER2-positive early or advanced BC (E/ABC). In-vitro experiments have shown that pyrotinib can effectively inhibit colony formation in HER2-low (IHC 2+/FISH negative) BC cells. This PILHLE-001 study (NCT05165225) aimed to evaluate the efficacy and safety of neoadjuvant pyrotinib plus chemotherapy in HR-positive/HER2-low (IHC 2+/FISH negative) EBC patients with potential biomarkers. Methods: PILHLE-001, as a single-arm, single-center phase Ⅱ trial, enrolled patients with previously untreated HR-positive (ER or PR > 1%) and HER2-low (IHC 2+/FISH negative) invasive EBC (TNM stage II-III) to receive pyrotinib 320mg QD and four Q3W of epirubicin-cyclophosphamide followed by four Q3W of docetaxel. MammaPrint/BluePrint at baseline (t0) was assessed. Breast magnetic resonance imaging (MRI) was conducted at t0, the end of cycle 2 neoadjuvant therapy (t1), and the end of all neoadjuvant therapy. Immune cell subpopulations assay and gene sequencing of tumor tissues with whole blood control samples were performed at t0 and surgery (t2). Additional core biopsy was administered to reassess Ki67 and tumor infiltrating lymphocytes (TILs) at t1. The primary outcome was RCB 0/I rate. The short-term secondary outcomes included pathological complete response (pCR, ypT0/is ypN0) rate, objective response rate (ORR), breast conservation surgery (BCS) rate, safety, and exploratory biomarkers analysis. Results: From July 2021 to March 2023, 48 patients were enrolled and treated. The median age of the patients was 48 years (range 28-66), 43 (90%) had cT1-2 tumors, 30 (63%) showed no node involvement, 37 (77%) had tumours with TNM stage II, and 47 (98%) had ER expression ≥ 50%. Twenty-eight (61%) of 46 patients had MammaPrint high risk. Out of the 48 patients, 26 (54.2%) achieved RCB 0/I, with a 95% confidence interval of 39.2% to 68.6%. The RCB 0/I rate was particularly higher in tumors with no lymph node involvement (73.3%), TNM stage II (64.9%), or abundant tumor-infiltrating lymphocytes (66.7%). Three (6.3%) patients obtained a pCR. The rate of BCS was 60.4% (29/48). The ORR was 45.8% (22/48) at t1 and 81.3% (39/48) at the end of all neoadjuvant therapy, respectively. No patients had progressive disease. All treatment-related adverse events (AEs) were mostly of grade 1 or 2 severity. Grade ≥ 3 AEs occurred in 21 (44%) patients, with the most prevalent being diarrhea [10 (21%)]. All AEs were reversible with symptomatic treatment and no treatment-related deaths occurred. Patients with MammaPrint risk-low BC had a lower RCB 0/I rate than those with risk-high BC (60.7% vs. 44.4%), although the difference was not statistically significant. Baseline specific immune cell subpopulations (lower PD-1, higher CD3, etc.) or the presence of non-altered PIK3CA were significantly associated with a higher likelihood of achieving RCB 0/I. Similarly, objective response, greater declines in specific MRI quantitative parameters (Ktrans and Kep), greater declines in Ki67, or more increased TILs at t1 were also significantly associated with a higher rate of RCB 0/I. Conclusions: The PILHLE-001 trial first revealed that neoadjuvant pyrotinib plus chemotherapy has encouraging efficacy and acceptable toxicity in patients with HR-positive/HER2-low (IHC 2+/FISH negative) EBC, and this regimen warrants further investigation in phase III randomized controlled trials. Citation Format: Chang Gong, Yuan Xia, Yingying Zhu, Yaping Yang, Wenqian Yang, Louis W.C. Chow, Li Ling, Yunjie Zeng, Jiajie Zhong, Ziliang Cheng, Jun Shen, Qun Lin, Yinduo Zeng, Qiang Liu, Erwei Song. PILHLE-001: neoadjuvant pyrotinib combined with chemotherapy in HR-positive, HER2-low (IHC 2+/FISH-negative) early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-28-04.

Abstract PO3-28-05: Therapeutic Plasmapheresis as a Symptomatic Treatment for Paclitaxel-Associated Peripheral Polyneuropathy

Abstract Relevance: Paclitaxel-associated peripheral polyneuropathy (PIPN) is one of the most common side effects that develop during treatment with drugs of the taxane group. In the treatment of early breast cancer with paclitaxel 80 mg/m2 weekly, 12 injections, PINP develops in 90% of patients of varying severity. The main symptoms are pain and numbness in the arms and legs, which is associated with the accumulation of paclitaxel in the ganglia of the spinal cord, as well as increased expression in the ganglia of the spinal cord of chemokines and cytokines, such as IL-1β, IL-8 and TNF-α, as well as CXCR4, RAGE, CXCL1, CXCL12, CX3CL1 and C3. We hypothesized that the severity of PIPN symptoms can be reduced by lowering the concentration of chemokines and cytokines in the blood by performing plasmapheresis sessions. Research methods: An open prospective study was carried out, the protocol of which was approved by the ethical committee. The study included 30 patients (100% women) aged 30 to 60 years (mean age 45 years) who developed PIPN during paclitaxel therapy 80 mg/m2, weekly, 12 injections. The severity of PIPN symptoms was assessed using a “visual analogue scale” (VAS). The results of the VAS evaluation varied from 6 to 8 points. Patients underwent 5 courses of membrane plasmapheresis with exfusion of 400-500 ml of plasma per session (20 ml per 1 kg of body weight), plasma loss was compensated with saline. Repeated procedures were performed once every two months for 6 months. Results: 30 patients underwent 15 procedures of therapeutic plasmapheresis within 6 months. In 21 patients (70%) there was a pronounced decrease in PIPN symptoms (VAS - 2-3 points), in 3 patients (10%) a moderate decrease in symptoms (VAS -5-6 points), in 6 (20%) no effect of plasmapheresis (VAS - 7-8 points). Approximately 15% of procedures were associated with adverse events, the most common of which were vasovagal reactions; 20% of patients had at least one adverse event. Conclusions: Given the subjective reduction in the severity of PIPN symptoms during courses of therapeutic plasmapheresis in more than 70% of cases, therapeutic plasmapheresis can be used as a symptomatic therapy for PIPN, however, taking into account the subjective assessment of the results by patients, there may be a risk of developing cognitive errors. Therefore, this method of therapy requires more thorough study. Citation Format: Sardor Abdugafforov, Vladimir Vorotnikov, Alexander Soynov, Tornike Mchedlidze, Igor Kopytich, Sofia Kim. Therapeutic Plasmapheresis as a Symptomatic Treatment for Paclitaxel-Associated Peripheral Polyneuropathy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-05.

The landscape of real-world evidence of rituximab utilization and clinical outcomes in patients with cancer, rheumatoid arthritis, and multiple sclerosis: A scoping review.

Rituximab (RTX) is an anti-CD20 monoclonal antibody that is used to treat various conditions in cancer, rheumatoid arthritis (RA), and multiple sclerosis (MS). Although RTX has been used in the United States for almost 3 decades, questions remain regarding its real-world utilization and effectiveness. To describe the state of observational research and real-world evidence evaluating RTX in oncology, RA, and off-label use in MS. A broad search was conducted in MEDLINE, Embase, and CINAHL covering the period of January 2010 to June 2022. Two reviewers independently screened all identified records for each disease category (cancer, RA, MS) beginning with title review, followed by abstract, and full-text review to identify relevant publications to include in the final analysis. Data were extracted and summarized for each disease based on overall trends, similarities, and differences across included studies and stratified by disease state. A total of 260 studies met eligibility criteria, with 79 studies for the RA cohort, 144 for cancer, and 37 for MS. Across all disease cohorts, most studies (n = 189; 72.7%) were retrospective. 171 (65.8%) studies used hospital or electronic health record data as their data source and 65 (23.2%) used registry databases. Most studies (n = 153; 58.8%) assessed the effectiveness of RTX measured by disease-specific endpoints, followed by safety (n = 60; 23.1%), treatment patterns (n = 32; 12.3%), and descriptive analyses assessing treatment adherence and economic burden of disease (n = 16; 6.2%). Although safety was not the primary outcome for most studies, the majority of studies across all disease states still reported some form of safety measure. Conclusive statements on RTX's benefit varied across disease states, with MS having the most (n = 30; 81.1%) studies suggesting the drug's positive benefit. There were limited studies assessing RTX use, associated economic burden, and biosimilar switching. The findings underscore the need for health care providers to better understand the treatment landscape and utilization of RTX, particularly in terms of patient selection, timing of initiation, and long-term outcomes. Real-world evidence can help support health care decisions and treatment using rituximab.

Cutaneous manifestations of hypothyroidism: An observational study in a tertiary care center of Eastern India

Cutaneous manifestations of hypothyroidism: An observational study in a tertiary care center of Eastern India

Molecular docking of gingerol and shogaol for immunomodulatory effect in lupus disease

Background: One of the autoimmune diseases associated with high mortality is lupus or Systemic Lupus Erythematosus (SLE). In addition to symptomatic therapy, the treatment management of this condition includes immunomodulatory therapy. Various studies have been carried out on immunomodulators from natural products. Ginger rhizome (Zingiber officinale Roxb.) is a plant with potential immunomodulatory activity. Shogaol, which gives a spicy taste, is a metabolite of gingerol, a marker compound in ginger. Both of these compounds become important components of pharmacological activity. Objective: This study aimed to determine the in silico immunomodulatory activity of gingerol and shogaol compounds contained in ginger against S100A9, CTLA-4, SRSF1, JAK3, and MYD88 receptors. Method: In silico, a test was carried out using Pymol and PyRx applications, and receptors were involved in developing the immune system and SLE disease. Result: Docking results showed negative binding affinity and an RMSD of 2˚Angstroms. The shogaol, gingerol, and tofacitinib had several amino acid residues in common. Conclusion: In-silico analysis suggests that shogaol and gingerol could modulate the immune response against lupus. The resulting protein residues were similar between shogaol, gingerol, and the control, supporting their potential for immunomodulatory activity against lupus disease.

Potential role of oxidative stress in pathogenesis of benign prostatic hyperplasia in male dogs.

The pathogenesis of benign prostatic hyperplasia (BPH) in dogs is still not fully understood. Some studies suggest that oxidative stress may have a potential role in the pathogenesis of BPH in dogs. Age-related hormonal changes may activate a chronic inflammatory response in the prostate. This causes the generation of reactive oxygen species (ROS) and results in oxidative stress. Excessive production of ROS results in DNA damage and hyperplastic transformation of prostatic cells. The use of antioxidants for improvement of treatment outcomes for canine PBH has been discussed. Further research is needed on the importance of oxidative stress in the development of BPH in dogs and the usefulness of antioxidants in the supportive treatment of this condition.

WOULD HYPERBARIC OXYGEN THERAPY BE A SUPPORTIVE TREATMENT METHOD FOR REFRACTORY IDIOPATHIC GRANULOMATOUS MASTITIS?

BackgroundRefractory IGM causes patients to use antibiotics, steroid therapy, immunosuppressive agents for a very long time and even leads to surgical procedures resulting in the loss of breast tissue. Hyperbaric Oxygen Therapy (HBOT) is a frequently used method in the treatment of wounds that are difficult to heal. We thought that HBOT would be an alternative treatment method for refractory IGM patients. MethodsIt is a retrospective cohort study on refractory IGM patients conducted at three tertiary care treatment centers between January 2021 and July 2023. The patients were evaluated in two groups: those who only took steroid treatment and those who received HBOT and steroid treatment. The demographic and clinical characteristics of the patients, the types of treatment applied and their responses to treatment were evaluated. ResultsThere were no significant differences generally in the demographic and clinical features in both groups. The incidence of multicentric GM was found to be higher in the HBOT group (66.67%; p = 0.044). Although the recovery results were similar in both groups, the average daily steroid dose and duration of drug use were found to be higher in the group receiving only steroid treatment (16 mg vs. 4 mg and 270 days vs. 30 days) (p<0.001). ConclusionIn our study, we showed for the first time in the literature that HBOT is effective in the treatment of refractory IGM patients. Our study needs to be supported by prospective studies evaluating cost effectiveness and possible long term complications..

Crimean-Congo Hemorrhagic Fever Virus for Clinicians-Diagnosis, Clinical Management, and Therapeutics.

Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread tickborne viral infection worldwide and has a fatality rate of up to 62%. Despite its widespread range and high fatality rate, no vaccines or treatments are currently approved by regulatory agencies in the United States or Europe. Supportive treatment remains the standard of care, but the use of antiviral medications developed for other viral infections have been considered. We reviewed published literature to summarize the main aspects of CCHFV infection in humans. We provide an overview of diagnostic testing and management and medical countermeasures, including investigational vaccines and limited therapeutics. CCHFV continues to pose a public health threat because of its wide geographic distribution, potential to spread to new regions, propensity for genetic variability, potential for severe and fatal illness, and limited medical countermeasures for prophylaxis and treatment. Clinicians should become familiar with available diagnostic and management tools for CCHFV infections in humans.

Frontotemporal dementia: from genetics to therapeutic approaches.

Frontotemporal dementia (FTD) includes a group of neurodegenerative diseases characterized clinically by behavioral disturbances and by neurodegeneration of brain anterior temporal and frontal lobes, leading to atrophy. Apart from symptomatic treatments, there is, at present, no disease-modifying cure for FTD. Three main mutations are known as causes of familial FTD, and large consortia have studied carriers of mutations, also in preclinical Phases. As genetic cases are the only ones in which the pathology can be predicted in life, compounds developed so far are directed toward specific proteins or mutations. Herein, recently approved clinical trials will be summarized, including molecules, mechanisms of action and pharmacological testing. These studies are paving the way for the future. They will clarify whether single mutations should be addressed rather than common proteins depositing in the brain to move from genetic to sporadic FTD.

Helicobacter cholecystus bacteremia in an adult with acute cholecystitis.

We report the isolation of Helicobacter cholecystus from a positive blood culture from a 58-year-old man in China who had bacteremia and acute cholecystitis. The patient's condition improved after symptomatic support treatment and subtotal cholecystectomy. This finding suggests that H. cholecystus should be considered as potential human pathogens.

Pulmonary Infundibular Stenosis Secondary to a Mediastinal Hodgkin Lymphoma Tumor Invasion in a Young Adult Male: What a Rare Occurrence!

Introduction: Cardiac involvement is a rare unusual localization of Hodgkin lymphoma, as it’s known that primary lymphomas of the heart are rare. They develop primarily in the right atrium, and extend to the pericardium in about one third of the cases. Pulmonary infundibular stenosis secondary to mediastinal mass Hodgkin lymphoma invasion is rare but not impossible especially in relapse cases. Case Report: A rare case of a young adult patient diagnosed with Hodgkin Lymphoma under chemotherapy presents a relapse of his pathology associated with heart failure; predominantly, right heart failure due to extension of the mediastinal mass tumor to the right cavities of the heart causing pulmonary infundibular stenosis which is a rare occurrence. He was put under an intense chemotherapy and symptomatic heart failure treatment with close follow-up after multi-disciplinary discussions including cardiologist, onco-hematologists and cardiothoracic surgeons. Three months later, a significant reduction of the mass was observered. Conclusion : Pulmonary infundibular stenosis secondary to mediastinal Hodgkin lymphoma invasion is a rare entity of secondary tumors of the heart. Multimodal imagery is the key tool for diagnosis. There prognosis depend on multiple factors but generally good in younger adult patients compared to aged individuals.

Development of an emulsion composition with fennel and caraway essential oils for use in the combined therapy of ulcerative colitis

The aim of the study is to develop the composition of an emulsion containing essential oils of Fennel and Caraway seeds for use in the symptomatic complex therapy of ulcerative colitis with the aim of eliminating functional intestinal disorders. Materials and methods. The objects of the study were samples of emulsions containing active pharmaceutical ingredients (essential oils of Fennel and Caraway), purified water, oils (refined sunflower oil, refined olive oil, refined sesame oil), emulsifiers (polyethylene glycol 40 hydrogenated castor oil, polysorbate 80, polyethylene glycol 100 stearate, acacia gum, guar gum, xanthan gum, soya lecithin), viscosity regulator - apple pectin and flavouring agents (food additives with cherry and tarragon flavour). Organoleptic properties, stability, rheological parameters, pH, particle size determination by microscopy, and a taste test were carried out with model emulsion samples. Research to establish the optimal technological parameters was carried out in parallel. Results. The main parameters of the technological process have been established, which allow to obtain an emulsion with evenly distributed particles: 15 minutes at maximum speed. The concentration of emulsifiers at which the emulsions are stable was selected. It was found that the samples containing polyethylene glycol 100 stearate, gums, and soy lecithin have satisfactory organoleptic properties. The sample with soy lecithin emulsifier differs from the others in its ability to form microemulsions, but it has low viscosity. To improve the rheological properties, apple pectin was added to the emulsion. The taste test showed that among vegetable oils, refined sesame oil has a more neutral taste, and the flavouring additive "Tarkhun" balances the taste better. The release of active pharmaceutical ingredients (APIs) from the emulsion base was confirmed by thin-layer chromatography. Conclusions. A microemulsion with essential oils based on refined sesame oil, soy lecithin, with the addition of viscosity and flavour correctors was developed. The obtained emulsion has satisfactory organoleptic properties and conforms to the requirements for emulsion quality indicators

Profound Alkalosis and Prolonged QT Interval Due to Inappropriate Gastrostomy Tube Loss: A Case Report

Introduction: Severe metabolic alkaloses are relatively rare but can carry a high mortality rate. Treatment involves supportive care and treatment of underlying causes. Case Report: A 55-year-old male dependent on a gastrojejunostomy tube presented to the emergency department for altered mental status. The patient had metabolic alkalosis, electrolyte abnormalities, and prolonged QT interval on electrocardiogram. Examination and history revealed that chronic drainage of gastric fluid via malfunctioning a gastrojejunostomy tube resulted in profound alkalosis. The patient recovered with supportive care, electrolyte repletion, and gastrojejunostomy tube replacement. Conclusion: This case highlights the importance of gastrointestinal acid-base pathophysiology.

Complex connective tissue convergence: A case report of scleroderma, systemic lupus erythematosus, and Sjögren's Syndrome overlap syndrome in an adolescent female

This case report illustrates the uncommon occurrence of an overlap syndrome involving systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Sjögren's syndrome in a 16-year-old female patient. Despite their distinct pathophysiological mechanisms and clinical manifestations, these connective tissue diseases converged in this patient, presenting a diagnostic challenge. The clinical presentation included features such as Raynaud's phenomenon, mouth and digit ulcers, alopecia, photosensitivity, and positive autoantibodies. Diagnostic workup revealed positive findings on antinuclear antibodies (ANA) and extractable nuclear antigen (ENA) panel, confirming the presence of autoantibodies associated with all three conditions. The patient was managed with a combination of symptomatic treatment, hydroxychloroquine, and prednisolone. This case underscores the complexity of overlapping autoimmune diseases and emphasizes the importance of a thorough clinical evaluation, appropriate diagnostic testing, and timely initiation of management to optimize patient outcomes.

A Case of Hypohidrotic Ectodermal Dysplasia in a 1-Year Old Filipino Male

Introduction: Hypohidrotic Ectodermal Dysplasia (HED) is the most common Ectodermal Dysplasia, a group of rare, inherited multisystemic disorders exhibiting developmental aberrations in ectodermal structures including the hair, teeth, nails, and sebaceous and sweat glands. HED is commonly X-linked, presenting with abnormalities of the hair and teeth accompanied by inability to sweat. This case report aims to present a case of X-linked HED in a 1-yearold Filipino male. Case Report: A 1-year-old Filipino male presented with reduced sweating since birth and heat intolerance. He had scalp and facial papules, slowly growing, sparse eyebrow and scalp hair, periorbital wrinkling with hyperpigmentation, everted lips, frontal bossing, absent tooth, and negative palmoplantar starchiodine test. Maternal male relatives had similar symptoms while females had little to no symptoms. He was diagnosed with HED. Skin punch biopsy with immunohistochemistry showed absence of eccrine glands on the plantar skin, which strengthened the diagnosis. Management of symptoms was mainly supportive and involved multidisciplinary collaboration with Pediatrics, Otorhinolaryngology, Dentistry, and Nutrition and Dietetics. Conclusion: This report underscores the critical role of Dermatologists in identifying key clinical signs of HED, which primarily relies on clinical assessment. A high level of suspicion is warranted when abnormalities in hair, teeth, and sweating are evident. It is crucial to consider other potential features in patients with symptoms of hypotrichosis, hypodontia and hypohidrosis, due to the varied manifestations of the disease. Early detection, comprehensive supportive treatment, and patient education are vital for improving the quality of life for those affected by HED.

Ebola Haemorrhagic Fever: An Overview

Ebola virus disease is a rare but severe, often fatal illness in humans. Fruit bats are the natural reservoirs of Ebola virus, and it is transmitted to humans from wild animals and spreads between humans. Ebola virus is a class A bioterrorism agent, known to cause highly lethal haemorrhagic fever. Clinical symptoms include fever, myalgia, headache followed by vomiting, diarrhea, hemorrhagic rash, bleeding, and multi-organ failure. Vaccines to protect against Ebola have been developed and used to control the spread of Ebola virus disease. Treatment is mainly early supportive care with rehydration and symptomatic treatment. Ebola virus is a neglected pathogen and the knowledge and scientific information on Ebola virus disease is relatively limited and received little attention. Better understanding of ebolavirus disease mechanisms is needed to guide development of drugs, vaccines, and treatment strategies. Hence this comprehensive review on Ebola virus is undertaken to provide an overview of its transmission, pathogenesis, clinical symptoms, differential diagnosis, laboratory diagnosis, treatment, vaccines and preventive aspects and to highlight its importance, and impact on public health and further research.

Radiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP

Background4-Aminopyridine (4AP) is a medication for the symptomatic treatment of multiple sclerosis. Several 4AP-based PET tracers have been developed for imaging demyelination. In preclinical studies, [11C]3MeO4AP has shown promise due to its high brain permeability, high metabolic stability, high plasma availability, and high in vivo binding affinity. To prepare for the translation to human studies, we developed a cGMP-compatible automated radiosynthesis protocol and evaluated the whole-body biodistribution and radiation dosimetry of [11C]3MeO4AP in non-human primates (NHPs).MethodsAutomated radiosynthesis was carried out using a GE TRACERlab FX-C Pro synthesis module. One male and one female adult rhesus macaques were used in the study. A high-resolution CT from cranial vertex to knee was acquired. PET data were collected using a dynamic acquisition protocol with four bed positions and 13 passes over a total scan time of ~ 150 min. Based on the CT and PET images, volumes of interest (VOIs) were manually drawn for selected organs. Non-decay corrected time-activity curves (TACs) were extracted for each VOI. Radiation dosimetry and effective dose were calculated from the integrated TACs using OLINDA software.ResultsFully automated radiosynthesis of [11C]3MeO4AP was achieved with 7.3 ± 1.2% (n = 4) of non-decay corrected radiochemical yield within 38 min of synthesis and purification time. [11C]3MeO4AP distributed quickly throughout the body and into the brain. The organs with highest dose were the kidneys. The average effective dose of [11C]3MeO4AP was 4.0 ± 0.6 μSv/MBq. No significant changes in vital signs were observed during the scan.ConclusionA cGMP-compatible automated radiosynthesis of [11C]3MeO4AP was developed. The whole-body biodistribution and radiation dosimetry of [11C]3MeO4AP was successfully evaluated in NHPs. [11C]3MeO4AP shows lower average effective dose than [18F]3F4AP and similar average effective dose as other carbon-11 tracers.