Clinical Observations Research Articles

HELLP syndrome as an interdisciplinary problem. Clinical observation

HELLP syndrome as an interdisciplinary problem. Clinical observation

The phosphatase inhibitor LB-100 creates neoantigens in colon cancer cells through perturbation of mRNA splicing

Perturbation of protein phosphorylation represents an attractive approach to cancer treatment. Besides kinase inhibitors, protein phosphatase inhibitors have been shown to have anti-cancer activity. A prime example is the small molecule LB-100, an inhibitor of protein phosphatases 2A/5 (PP2A/PP5), enzymes that affect cellular physiology. LB-100 has proven effective in pre-clinical models in combination with immunotherapy, but the molecular underpinnings of this synergy remain understood poorly. We report here a sensitivity of the mRNA splicing machinery to phosphorylation changes in response to LB-100 in colorectal adenocarcinoma. We observe enrichment for differentially phosphorylated sites within cancer-critical splicing nodes of U2 snRNP, SRSF and hnRNP proteins. Altered phosphorylation endows LB-100-treated colorectal adenocarcinoma cells with differential splicing patterns. In PP2A-inhibited cells, over 1000 events of exon skipping and intron retention affect regulators of genomic integrity. Finally, we show that LB-100-evoked alternative splicing leads to neoantigens that are presented by MHC class 1 at the cell surface. Our findings provide a potential explanation for the pre-clinical and clinical observations that LB-100 sensitizes cancer cells to immune checkpoint blockade.

Association between Lipid-Lowering Drugs and Traumatic Subdural Hemorrhage: A Mendelian Randomization Study.

There are current clinical observations that atorvastatin may promote subdural hematoma resorption. We aimed to assess the causal effects of lipid-lowering agents 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, Proproteinconvertase subtilisin/kexin type 9 (PCSK9) inhibitors and Niemann-Pick C1-like protein 1 (NPC1L1) inhibitors on traumatic subdural hematomas. We used genetic instruments to proxy lipid-lowering drug exposure, with genetic instruments being genetic variants within or near low-density lipoprotein (LDL cholesterol)-associated drug target genes. These were analyzed by using a two-sample Mendelian randomization (MR) study. A causal relationship was found between HMGCR inhibitors and traumatic subdural hematoma (Inverse variance weighted (β = -0.7593341 (Odds Ratio (OR) = 0.4679779), p = 0.008366947 < 0.05)). However, no causal relationship was found between PCSK9 inhibitors and NPC1L1 inhibitors and traumatic subdural hematoma (PCSK9 inhibitors: Inverse variance weighted (β = 0.23897796 (OR = 1.2699505), p = 0.1126327), NPC1L1 inhibitors: Inverse variance weighted (β = -0.02118558 (OR = 0.9790373), p = 0.9701686)). Sensitivity analysis of the data revealed good stability of the results. This two-sample MR study suggests a potential causal relationship between HMGCR inhibition (atorvastatin) and traumatic subdural hemorrhage.

The Ketogenic Diet in DEPDC5-related Epilepsies: Clinical and Preclinical Observations (P2-1.002)

The Ketogenic Diet in DEPDC5-related Epilepsies: Clinical and Preclinical Observations (P2-1.002)

B cells and the stressed brain: emerging evidence of neuroimmune interactions in the context of psychosocial stress and major depression.

The immune system has emerged as a key regulator of central nervous system (CNS) function in health and in disease. Importantly, improved understanding of immune contributions to mood disorders has provided novel opportunities for the treatment of debilitating stress-related mental health conditions such as major depressive disorder (MDD). Yet, the impact to, and involvement of, B lymphocytes in the response to stress is not well-understood, leaving a fundamental gap in our knowledge underlying the immune theory of depression. Several emerging clinical and preclinical findings highlight pronounced consequences for B cells in stress and MDD and may indicate key roles for B cells in modulating mood. This review will describe the clinical and foundational observations implicating B cell-psychological stress interactions, discuss potential mechanisms by which B cells may impact brain function in the context of stress and mood disorders, describe research tools that support the investigation of their neurobiological impacts, and highlight remaining research questions. The goal here is for this discussion to illuminate both the scope and limitations of our current understanding regarding the role of B cells, stress, mood, and depression.

Model-based closed-loop control of thalamic deep brain stimulation.

Introduction: Closed-loop control of deep brain stimulation (DBS) is beneficial for effective and automatic treatment of various neurological disorders like Parkinson's disease (PD) and essential tremor (ET). Manual (open-loop) DBS programming solely based on clinical observations relies on neurologists' expertise and patients' experience. Continuous stimulation in open-loop DBS may decrease battery life and cause side effects. On the contrary, a closed-loop DBS system uses a feedback biomarker/signal to track worsening (or improving) of patients' symptoms and offers several advantages compared to the open-loop DBS system. Existing closed-loop DBS control systems do not incorporate physiological mechanisms underlying DBS or symptoms, e.g., how DBS modulates dynamics of synaptic plasticity. Methods: In this work, we propose a computational framework for development of a model-based DBS controller where a neural model can describe the relationship between DBS and neural activity and a polynomial-based approximation can estimate the relationship between neural and behavioral activities. A controller is used in our model in a quasi-real-time manner to find DBS patterns that significantly reduce the worsening of symptoms. By using the proposed computational framework, these DBS patterns can be tested clinically by predicting the effect of DBS before delivering it to the patient. We applied this framework to the problem of finding optimal DBS frequencies for essential tremor given electromyography (EMG) recordings solely. Building on our recent network model of ventral intermediate nuclei (Vim), the main surgical target of the tremor, in response to DBS, we developed neural model simulation in which physiological mechanisms underlying Vim-DBS are linked to symptomatic changes in EMG signals. By using a proportional-integral-derivative (PID) controller, we showed that a closed-loop system can track EMG signals and adjust the stimulation frequency of Vim-DBS so that the power of EMG reaches a desired control target. Results and discussion: We demonstrated that the model-based DBS frequency aligns well with that used in clinical studies. Our model-based closed-loop system is adaptable to different control targets and can potentially be used for different diseases and personalized systems.

Developmental trajectories of GABAergic cortical interneurons are sequentially modulated by dynamic FoxG1 expression levels

GABAergic inhibitory interneurons, originating from the embryonic ventral forebrain territories, traverse a convoluted migratory path to reach the neocortex. These interneuron precursors undergo sequential phases of tangential and radial migration before settling into specific laminae during differentiation. Here, we show that the developmental trajectory of FoxG1 expression is dynamically controlled in these interneuron precursors at critical junctures of migration. By utilizing mouse genetic strategies, we elucidate the pivotal role of precise changes in FoxG1 expression levels during interneuron specification and migration. Our findings underscore the gene dosage-dependent function of FoxG1, aligning with clinical observations of FOXG1 haploinsufficiency and duplication in syndromic forms of autism spectrum disorders. In conclusion, our results reveal the finely tuned developmental clock governing cortical interneuron development, driven by temporal dynamics and the dose-dependent actions of FoxG1.

Infiltration of Round Blue Cell Tumors in Bone Marrow

Objective: To identify different types of round blue cell tumors on bone marrow biopsy and their pattern of marrow infiltration. Methodology: This cross-sectional descriptive study was conducted at the Department of Hematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from July 2021 to December 2021. A total of 60 diagnosed cases of round blue cell tumors were included. Patients with acute lymphoblastic leukemia (ALL) and those receiving treatment for round blue cell tumors were excluded. Bone marrow aspiration and biopsy were performed. Peripheral film results, clinical observations, and patterns of marrow infiltration of round blue cell malignancies were analyzed using Statistical Package for the Social Sciences (SPSS) version 23. Results: The study revealed a male to female ratio of 2:1, with 40 (66.6%) males and 20 (33.3%) females. The overall average age was 5.69 ± 5.0 years. Ewing sarcoma and rhabdomyosarcoma patients did not exhibit infiltration, while three instances of retinoblastoma (9.37%) and two cases of neuroblastoma (10.52%) did. Immunohistochemistry (IHC) results for synaptophysin and chromogranin were positive for retinoblastoma and neuroblastoma, while S100 results were positive for neuroblastoma infiltration and negative for retinoblastoma. Both retinoblastoma and neuroblastoma showed diffuse, focal, and interstitial patterns of infiltration on trephine biopsy. Conclusion: Small round blue cell tumors were noted in bone marrow infiltration in 5 (8.33%) cases. Early detection of malignant cancers necessitates appropriate medical care, and in more severe cases, the need for neoadjuvant chemotherapy.

Clinical features and temporal CT findings in patients with Branchio-Oto-Renal or Branchio-Oto Syndrome

Objective: To assess the clinical features and CT diagnostic characteristics of Branchio-Oto-Renal or Branchio-Oto Syndrome. Methods: The temporal CT findings and clinical features observations of 13 patients with Branchio-Oto-Renal Syndrome (BORS) or Branchio-Oto Syndrome(BOS) confirmed by genetic testing were retrospectively analyzed. There were 8 males and 5 females, aged from 1 to 39 years, with a median age of 9 years, in which 3 pairs (6 cases) were parent-child relationship. Results: All of 13 cases had hearing loss and preauricular fistula, 11 cases accompanied by 2nd branchial fistulas. There were 20 ears of mixed hearing loss, 3 ears of sensorineural hearing loss, and 2 ears of conductive hearing loss. The mutation point of gene testing was located in EYA1 in 12 cases and SIX1 in 1 case. Twenty ears showed gradually narrowing of the diameter of basal turn, with hypoplasia in the second turn and aplasia in apical turn. There were irregular wall of vestibule and horizontal semicircular canal in 10 ears,widened vestibular in 7 ears, and vestibular fusion with horizontal semicircular canal in 3 ears. Three ears had an enlarged vestibular aqueduct, 8 ears showed enlargement of internal auditory canal. Seventeen ears had adhesion of malleolus to tympanic cavity. Six ears could not measured the incudostapedial joint angle by reason of tympanic inflammatory cover, 3 ears could not show incudostapedial joint, and 8 ears showed the incudostapedial joint angle more than 122°. Six ears showed poor oval window, and 1 ear had poor round window. Eighteen ears showed distended eustachian tube, and accompanied by tympanic or mastoiditis in 11 ears. Anterolateral shift of tympanum was found in 22 ears, 17 ears had low middle cranial fossa, and 3 ears had stenotic external auditory canal. Conclusions: Cochlear dysplasia, ossicular chain malformation and distended eustachian tube comprise the characteristic CT signs of BOS/BORS, which possesses versatile and complex CT findings. Temporal CT can accurately assess the important structures such as cochlea, ossicles, vestibule, semicircular canal, vestibular aqueduct and internal auditory canal. Combing with the clinical characteristics of bilateral, mixed hearing loss, preauricular fistula and branchial fistula can provide valuable information for early diagnosis and treatment.

Multimodal radiology diagnostics for recurrent congenital diaphragmatic hernia in a child with congenital heart disease: clinical case

Congenital diaphragmatic hernia (CDH) is a severe congenital malformation that occurs as a result of delayed closure of the pleuroperitoneal canal or the diaphragm failure, which leads to the displacement of abdominal organs into the thoracic cavity. Timely diagnosis of recurrent diaphragmatic hernia in the long-term period causes great difficulties. The article presents a clinical observation of a 1-year-and-8-months old female patient operated on for false congenital diaphragmatic hernia and congenital heart defect during the newborn period. Chest X-ray at the outpatient stage allowed diagnosing a relapse of CDH and determining the urgency of hospitalization. In the hospital, the diagnosis was confirmed by computed tomography, surgical treatment was performed.

COCCOS study: Developing a transition program for adolescents with chronic conditions using Experience-Based Co-Design. A study protocol.

During adolescence, adolescents and young adults (AYAs) are expected to transfer their care from the pediatric environment towards an adult-focused setting. To prevent an abrupt transfer of care, it is recommended to provide AYAs with chronic conditions an adequate transition program. The aim of this paper is to describe the study protocol for the development of a transition program for AYAs with common chronic conditions (COCCOS study), using the Experience-Based Co-Design (EBCD) methodology. A qualitative, participatory study is conducted in Flanders (Belgium). Study participants are AYAs (n≥15, 14-25 years old, diagnosed with type 1 diabetes, asthma, or obesity), their families, and healthcare providers (n≥15). The study is composed of eight EBCD stages: clinical site observations, in-depth interviews, trigger film, healthcare providers' feedback event, AYAs' feedback event, joint event, co-design workshops, and a celebration event. Photovoice will take place as a starting point of EBCD. Data will be analyzed using thematic analysis. Data collection has started in January 2023 and is expected to be completed in May 2024. As of August 2023, over 15 clinical site observations have been conducted. A total of 18 AYAs, two parents, six healthcare providers have been enrolled and a total of 20 interviews have been conducted. Advancing transitional care is essential for tackling negative health outcomes. Applying the innovative participatory EBCD methodology will reveal key elements of transitional care for AYAs with common chronic conditions in the development of a person-centered transition program. Study findings will apply key elements of transitional care of AYAs with chronic conditions in the development of an adequate transition program.

Abstract LB123: Conditionally active, therapeutic lymphotoxin beta receptor (LTBR) agonist bispecific antibodies for induction of tertiary lymphoid structures in the treatment of solid tumors

Abstract The presence of tertiary lymphoid structures (TLS) and associated high endothelial venules (HEV) in the tumor microenvironment strongly correlates with improved prognosis and treatment outcomes across a wide range of solid tumors. These clinical observations, now replicated repeatedly, highlight the therapeutic potential of induction of TLS and/or boosting TLS functions, which include acting as a point of entry and education for immune effector cells locally in the tumor. Lymphotoxin beta receptor (LTBR) signalling is essential for lymphoid structure development and the ectopic expression of its ligands, lymphotoxin αβ and LIGHT, is sufficient for TLS formation in vivo but challenging for therapeutic development. Here we present human bispecific antibodies (bsAbs) which conditionally agonize LTBR on co-engagement of fibroblast activation protein (FAP), a tumor microenvironment specific marker expressed by cancer associated fibroblasts. In vitro characterisation of these therapeutic bsAbs is presented, along with in vivo preclinical evaluation of surrogate bsAbs binding to mouse LTBR and mouse FAP in murine tumor models. Results - Therapeutic bsAbs were identified following an extensive screening campaign combining LTBR and FAP binding arms on an engineered human Fc with minimal FcyR binding. In vitro assays using primary cancer associated fibroblasts and LTBR positive cells demonstrated conditionally active therapeutic bsAbs potently activated LTBR in the presence of FAP expressing cells, whereas in the absence of FAP expressing cells no activity was observed. Surrogate bsAbs demonstrated monotherapy activity and led to tumor regressions in combination with anti-PDL1 therapy in an EMT6 mouse model, a syngeneic orthotopic model of breast cancer. Flow cytometry of endpoint tumors showed robust formation of HEVs and increased infiltration of T cells and B cells. In addition, we demonstrate that LTBR agonism, but not PD-L1 inhibition, leads to the formation of TLS structures containing organized lymphocyte aggregates with the appearance of germinal centres and accumulations of T and B cells in a mouse model of lung cancer. In conclusion, conditionally active FAP-LTBR bispecifics activate LTBR in the tumor microenvironment and induce HEV and TLS formation, leading to potent monotherapy activity in vivo, and to tumor regression in combination with PD-L1. These data support the development of FAP-LTBR bispecifics for the treatment of solid tumors as monotherapy and in combination with standard of care. Citation Format: Marta Lewandowska, Fevzi Demircioglu, Lucy Penfold, Rebecca B. Riddle, Sameer Sirohi, Floriane Laurent, Richard Brown, Sonia Bains, Dara Bevan, Emma Stanley, Jeanine Pignatelli, James W. Legg, Ray Jupp. Conditionally active, therapeutic lymphotoxin beta receptor (LTBR) agonist bispecific antibodies for induction of tertiary lymphoid structures in the treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB123.

A combined musculoskeletal and finite element model of a foot to predict plantar pressure distribution

In this study, a combined subject-specific numerical and experimental investigation was conducted to explore the plantar pressure of an individual. The research utilized finite element (FE) and musculoskeletal modelling based on computed tomography (CT) images of an ankle-foot complex and three-dimensional gait measurements. Muscle forces were estimated using an individualized multi-body musculoskeletal model in five gait phases. The results of the FE model and gait measurements for the same subject revealed the highest stress concentration of 0.48 MPa in the forefoot, which aligns with previously-reported clinical observations. Additionally, the study found that the encapsulated soft tissue FE model with hyper-elastic properties exhibited higher stresses compared to the model with linear-elastic properties, with maximum ratios of 1.16 and 1.88 MPa in the contact pressure and von-Mises stress, respectively. Furthermore, the numerical simulation demonstrated that the use of an individualized insole caused a reduction of 8.3% in the maximum contact plantar pressure and 14.7% in the maximum von-Mises stress in the encapsulated soft tissue. Overall, the developed model in this investigation holds potential for facilitating further studies on foot pathologies and the improvement of rehabilitation techniques in clinical settings.

The Goettingen minipig as an experimental model in wound-healing studies

BackgroundDeep dermal wounds in extensive burns and chronic wound-healing disorders represent a significant medical problem and require a high level of therapy to reduce the risk of infection and other long-term consequences, such as amputation. A better understanding of the wound-healing processes is essential, and animal models are indispensable to fundamental research. ObjectiveThis study aimed to provide a transparent protocol and prove the effectiveness of an in vivo porcine model using Goettingen minipigs for wound-healing studies. Material and methodsThirteen female Goettingen minipigs were kept in species-appropriate housing and were treated according to the German law for the protection of animals. The study was performed with permission from the local ethical review committee of animal welfare. The experimental procedure for studying dermal regeneration in 102 full-thickness wounds through clinical observation and histological analysis, focusing on neodermal formation, is described in detail. ResultsThe Goettingen minipig model proved to be suitable in wound-healing studies. The dermal regeneration was evident and viewable without wound contamination or any rejection reaction. The histological evaluations were also reliable and clearly presented the optimized wound healing of deep dermal wounds using the different therapeutic approaches. ConclusionGiven the great clinical need for alternative or complementary therapies, we considered the Goettingen minipig trial a reliable, ethically justifiable, effective, and reproducible in vivo model for wound-healing studies.

PBPK-PD model for predicting morphine pharmacokinetics, CNS effects and naloxone antagonism in humans.

Morphine and morphine-6-glucuronide (M6G) produce central nervous system (CNS) effects by activating mu-opioid receptors, while naloxone is used mainly for the reversal of opioid overdose, specifically for the fatal complication of respiratory depression, but also for alleviating opioid-induced side effects. In this study we developed a physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) model to simultaneously predict pharmacokinetics and CNS effects (miosis, respiratory depression and analgesia) of morphine as well as antagonistic effects of naloxone against morphine. The pharmacokinetic and pharmacodynamic parameters were obtained from in vitro data, in silico, or animals. Pharmacokinetic and pharmacodynamic simulations were conducted using 39 and 36 clinical reports, respectively. The pharmacokinetics of morphine and M6G following oral or intravenous administration were simulated, and the PBPK-PD model was validated using clinical observations. The Emax model correlated CNS effects with free concentrations of morphine and M6G in brain parenchyma. The predicted CNS effects were compared with observations. Most clinical observations fell within the 5th-95th percentiles of simulations based on 1000 virtual individuals. Most of the simulated area under the concentration-time curve or peak concentrations also fell within 0.5-2-fold of observations. The contribution of morphine to CNS effects following intravenous or oral administration was larger than that of M6G. Pharmacokinetics and antagonistic effects of naloxone on CNS effects were also successfully predicted using the developed PBPK-PD model. In conclusion, the pharmacokinetics and pharmacodynamics of morphine and M6G, antagonistic effects of naloxone against morphine-induced CNS effects may be successfully predicted using the developed PBPK-PD model based on the parameters derived from in vitro, in silico, or animal studies.

Evaluation of risk factors of omphalitis in newborn beef calves with indoor housing

BackgroundOmphalitis is the third most common cause for diseases and infections in newborn calves. Its risk factors are well described in dairy production, but data in beef production is limited. ObjectiveTo identify and quantify the risk factors of omphalitis in cow-calf operations with seasonal indoor calving period. AnimalsNine hundred sixty-four calves included from 22 cow–calf operations in central France were included. MethodsA prospective cohort study involved data collection during two visits for each calf. Simple and multivariable logistic regression analyses evaluated the association between omphalitis and the variables. ResultsAmong 964 included calves, 311 (32.3%) calves had an omphalitis. Accounting for farms’ random effect, risk factors for omphalitis highlighted by the univariable analysis were: absence of navel disinfection (odds ratio (OR) = 2.3, [1.45–3.04]), wetness of bedding calving area (OR = 1.8–2.1, [0.78–2.83]-[0.63–3.57]), cleanliness of calves’ pen (OR =1.6–2.8, [1.22–2.27]-[2.02–3.84]), wetness of calves’ pen bedding (OR = 1.7–3.2, [1.12–2.06]-[3.08–3.84]), calf weight at birth >50 kg (OR = 2.0–5.0, [1.02–2.38]-[1.51–11.1]), umbilical cord length <3 cm (OR = 2.2–2.3, [1.53–3.11]-[1.24–4.38]), and sex (male vs female) (OR = 2.6, [2.08–3.69]). The multivariable analysis, accounting for farms’ random effect, showed that the absence of navel disinfection (OR= 2.2, [1.44–3.09]), wetness of bedding calving area (OR = 1.9–2.4, [0.55–2.83]-[0.59–3.28]), calf weight at birth >50 kg (OR = 1.9–2.6, [1.03–2.56]-[1.43–12.5]) and sex (male vs female) (OR =2.4, [2.09–3.49]) were risk factors for omphalitis. Conclusions and clinical importanceThese observations may help identify animals at early risk (>50 kg, male, short umbilical cord) and pay particular attention to the wetness of bedding and cleanliness of housing. This study highlights the importance of calving-pen bedding, calf characteristics and navel disinfection.

Does salivary pH affect postoperative sore throat in the head-down position of general anesthesia?

Tracheal intubation sometimes causes postoperative sore throat (POST) due to laryngeal damage. However, clinical observations suggest that the environment of the oral cavity may also affect POST. The purpose of this study was to investigate whether salivary pH in the oral cavity affects POST. After obtaining ethical approval, informed consent was obtained from all patients. Patients who underwent surgery in the supine position were enrolled as the control group. Patients who underwent laparoscopic surgery in the head-down position were enrolled as the intervention group. Immediately before both groups of patients were anaesthetised, expelled saliva was collected, and salivary pH was measured. Immediately postoperatively, the same measurement was carried out before the patient regained consciousness. The primary outcome was the change in salivary pH. The secondary outcome was POST. In our study, POST was defined as pharyngeal and swallowing pain in the glossopharyngeal and superior laryngeal nerves. The normal distribution of pH was tested using the Shapiro-Wilk test followed by analysis using repeated-measurements and one-way analysis of variance. Statistical significance was set at p < .05. A total of 62 patients were enrolled, of whom two were excluded based on the exclusion criteria. Salivary pH in the intervention group was significantly lower than that in the control group. Five patients had POST in the intervention group, whereas none had POST in the control group had POST. Acidotic-shifted saliva is considered one of the causes of POST.

Sinonasal diffuse large B-cell lymphoma: own clinical observation and literature review

Diffuse large B-cell lymphoma is the most common immunomorphological variant of lymphoma in adults. Extranodal lesions are observed in a third of patients at the disease onset. The organs most often involved are the gastrointestinal tract, testicles, bones, thyroid gland, and skin. Primary involvement of the nasal cavity and paranasal sinuses occur extremely rarely and cause diagnostic and therapeutic difficulties.The article demonstrates a rare clinical case of newly diagnosed diffuse large B-cell lymphoma with sinonasal tract involvement. It took 6 months to verify the final diagnosis. At the moment, the induction stage of treatment for diffuse large B-cell lymphoma continues, the achieved complete metabolic response is maintained.

Neuro-regression Assessment- A Case Report

Introduction: Neuro-regression can occur for various reasons, including neurodegenerative diseases such as Alzheimer's disease, certain genetic disorders, brain injuries, infections, toxic exposures, or metabolic disorders. It is often characterized by a progressive deterioration of neurological function over time. Neuro-regression can be caused by a variety of factors, including, Neurodegenerative diseases, Genetic disorders, Brain injuries, Infections, Toxic exposures, and Metabolic disorders. Objective: The goal of this case report is to highlight the difference between developmental delay and developmental regression also known as Neuro-Regression in terms of differential diagnosis. Case Report: A 2.2-year-old male child, with a background of developmental delay and epilepsy was admitted with multiple episodes of breakthrough seizures. Developmental milestones were age-appropriate till 11 months of age (before the seizure). After the seizure, the child’s motor development regressed and the child was not able to sit, or stand. The speech and language milestones were appropriate to the age before the seizure and regressed after the seizure. Conclusion: In our study, it's very clear that the child experiencing neuro-regression which is evident based on the parents’ report, previous and present clinical assessments as well and clinical observation. Regression is an indication that more investigation is necessary and team members like a Developmental Paediatrician, Neurologist, and Clinical Psychologist should be involved.

Vision Loss in the Elderly: Focus on Giant Cell Arteritis (Clinical Observation)

Introduction: Giant cell (temporal) arteritis (GCA) is a cell-mediated vasculitis that damages the major blood vessels such as an aorta with its major branches and mainly extracranial branches of the carotid artery. Vision loss that can be caused by the anterior ischemic optic neuropathy (AION) or by the central retinal artery occlusion (CRAO) is considered to be one of the most terrible complications of the GCA. In the represented clinical case the complete vision loss was the cause of hospitalization of the patient and the basis for a diagnosis of GCA at the same time. The episodes of the reversible visual impairment that were observed 9 days before the hospitalization attract attention to themselves.Purpose. to pay attention to the main ophthalmological and general symptoms that let the doctor to suspect this disease during the primary reception and to carry out diagnostics promptly to start timely treatment.Conclusion. The main criteria for diagnosis of GCA in the practice of ophthalmologists are female gender, age over 50 years, intense headache with paresthesia, pain in the lower jaw during chewing and short-term episodes of vision loss. Clinical blood test including erythrocyte sedimentation rate, C-reactive protein level and platelet count are the necessary laboratory diagnostic methods.