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Nov 2025 DOI 10.14302/issn.2470-0436.jos-25-5503
H. Nelson MarkCorresponding author
Purpose Create a new diagnostic and therapeutic framework for patients with Exudative Age-Related Macular Degeneration (ARMD) and choroid imaging biomarkers of non-neovascular choroidal pathology who have persistent neovascular exudation during the course of monotherapeutic interventions. Methods Retrospective, longitudinal case series study of 25 eyes from 23 patients with the referral diagnoses of treatment resistant Exudative ARMD who had persistent neovascular exudation despite various monotherapies. Inclusion criteria required choroidal imaging biomarkers of non-neovascular pathology including a thickened subfoveal choroid (greater than 300 microns) and vessels (subjectively dilated choroidal vessels in Haller’s layer) on Optical Coherent Tomography (OCT), choroidal neovascularization on IVFA and OCT Angiography (OCTA), as well choroidal leakage noted on indocynanine green videoangiography (ICG). Treatment consisted of OCTA and ICG - Directed Photodynamic Therapy (PDT) Triple Therapy, hereafter described as Combination Therapy, to areas of choroidal hyperpermeability and choroidal neovascularization. Combination therapy consisted of an anti-Vascular Endothelial Growth Factor (VEGF) intravitreal injection on Day 0 followed by half-fluence PDT and 2 mg intravitreal triamcinolone acetonide on Day 3-14. Results All study patients had treatment resistant Exudative ARMD defined as persistent subretinal and/or intraretinal fluid during their course of monotherapeutic interventions. Complete resolution of all exudation occurred in 23 eyes (92.0%) at 8 weeks. The mean duration of action was 155.6 weeks, with 72.0% of eyes leak free greater than 100 weeks. The mean vision at baseline was 0.46 ± 0.42 LogMAR, best corrected visual acuity (BCVA). 8 weeks after treatment, the vision was 0.35 ± 0.38 LogMar, an improvement of over one line, and this was maintained at one year. The baseline central subfield thickness (CST) was 296.4 ± 136.1 microns and improved by 111.4 ± 105.4 microns at 8 weeks after treatment. Treatment duration was negatively associated with the Caucasian race. Conclusions Patients with subretinal and/or intraretinal fluid secondary to Exudative ARMD should have a complete baseline multimodality imaging study to confirm the presence of neovascularization and whether choroidal hyperpermeability coexists. This study shows that patients with Exudative ARMD and persistent neovascular exudation despite monotherapuetic interventions often have choroidal biomarkers of non-neovascular choroidal pathology and that ICG and OCTA-directed PDT Triple Therapy resulted in complete resolution of all exudation in 92.0% of patients at 8 weeks with a reduction in central subfield thickness (CST) of 111.4 microns. The vision improvement at 8 weeks was 0.11 ± 0.38 LogMar and was sustained over 1 year. The mean duration of action was 155.6 weeks, with 72.0% of eyes leak free greater than 100 weeks. Additionally, this study shows that the treatment that addresses both pathological processes is successful and should be considered as a primary protocol when the biomarkers are present at baseline or as a secondary protocol if indeed the neovascular leakage is persistent despite monotherapy. Summary Patients with an Exudative ARMD with persistent neovascular exudation despite anti-VEGF monotherapy and who have imaging biomarkers of non-neovascular choroidal pathology often have two pathophysiological processes: choroidal hyperpermeability and angiogenesis. A proposed framework provides the rationale for OCTA and ICG-directed PDT Triple Therapy which successfully resolves 92% of the leakage that was persistent after various monotherapeutics.
Dec 2024
A Shaw NigelCorresponding author
The near-death experience (NDE) is an altered state of consciousness which arises when a person is critically ill or injured and possibly clinically dead. It should not be conflated with other mental events such as the deathbed vision or the fear or anticipation of death. Many believe that the NDE represents a genuine paranormal phenomenon providing a glimpse of an otherworldly existence and proof of an afterlife. Those who are skeptical of such a survivalist or supernatural interpretation have long pointed out that the core components of the NDE can be readily simulated with a variety of states, conditions and agents. In this conception, the NDE is reduced to no more or less than an extraordinarily complex hallucination. Since its rediscovery in the 1970s, multiple, often ingenious, attempts have been made to account for the NDE in such naturalistic or neuroscientific terms. None has so far proven completely satisfactory. One of the oldest, least considered but still promising is the CO2 theory which argues that a hypercarbic brain is a necessary precursor for the induction of a NDE. Supportive evidence that CO2 does play a pivotal role in the generation of the NDE can be gathered from diverse sources. These include: 1. measurement of blood gases; 2. Meduna’s now abandoned CO2 therapy; 3. analysis of the very limited number of pathophysiological conditions underlying the NDE; 4. recent discoveries of the role of 5-HT neurons in the central respiratory system. A model is proposed in which CO2 molecules are considered to be functionally equivalent to those of the classical hallucinogens (LSD, mescaline, psilocybin, dimethyltryptamine). These agents can mimic the phenomenology of the NDE with remarkable fidelity. What is still missing from any such explanation is the long-sought transduction mechanism which converts physical events into mental ones. This is a generic problem which confronts all attempts to explain the neurogenesis of mystical, psychedelic or visionary activity.
Apr 2024 DOI 10.14302/issn.2576-6694.jbbs-24-5001
Gianpaolo PisanoCorresponding author
Allergy, despite its stereotyped symptomatic manifestations, continues to pose significant etiological, pathophysiological, and therapeutic challenges. In the interface between the body and the environment, the respiratory pathway is particularly stressed from an allergological perspective. Under the relationship between energy and matter signed by Einstein, it is possible to approach patients suffering from allergies with an Electraceutical 1 administration in a quantum modality.
Jan 2021 DOI 10.14302/issn.2470-5020.jnrt-20-3619
Chen KepingCorresponding author
Professor, Jiangsu University, Zhenjiang, China
Circular RNAs (circRNAs) are recently rediscovered eukaryotic molecules that form a covalently closed-loop structure through a special type of alternative splicing known as backsplicing. These closed-loop structures are highly stable and resistant to RNase degradation, and are thereby expressed in a tissue-specific and evolutionarily conserved manner, which regulates the expression of proteins and mRNAs that are involved in the metabolic pathways associated with specific diseases. Recent evidence of the ubiquitous expression of circRNAs in cancer under physiological and pathophysiological conditions indicates that dysregulation of gene and protein expression might promote tumorigenesis and carcinogenesis, and that circRNAs have important clinical significance in the diagnosis, treatment, and prognosis of cancer and other diseases. This review provides a brief introduction to the characteristics, formation, and function of circRNAs. Some of circRNAs act as microRNA (miRNA) sponges to regulate the level of transcriptional splicing and the expression of parental genes through the circRNA-miRNA-mRNA regulation axis. We summarize recent progress in above-mentioned circRNAs associated with Alzheimer's disease (AD).
Nov 2020 DOI 10.14302/issn.2470-5020.jnrt-20-3596
Kombate DamelanCorresponding author
University of Kara (Togo)
Background Reversible posterior encephalopathy syndrome (RPE) is a clinical and radiological entity characterized by the acute or subacute fitting of symptoms covering headache, vomiting, visual disturbances, seizures and impairment of consciousness. The pathophysiology of RPE syndrome is poorly described. RPE syndrome is characterized by a reversible cerebral edema of often posterior topography in magnetic resonance imagery (MRI). Cases Presentation We consider RPE syndrome four cases under various conditions that are known as airplane flight, hypertension, non-steroidal anti-inflammatory medication, pregnancy and oldness with several pathologies. The RPE was described with several symptoms like headaches, vomiting, focal motor deficit, paresthesia, seizures, disorders of consciousness and photophobia. The imagery findings were varying from cortical hypersignals in Flair sequences to edema of both cortex and sub cortex. The outcome was good with a complete regression of symptoms and imagery lesions. Conclusion The pathophysiological mechanism of RPE syndrome remains unknown. High blood pressure, renal failure and drugs (anti-depressants, NSAIDs, immunosuppressants) are the most etiological factors. The diagnosis is based on clinical arguments and brain MRI. The main location is posterior. The clinical outcome was good with all the patients in our study, no recurrence was noted.
Jun 2020 DOI 10.14302/issn.2574-4526.jddd-20-3410
Darouichi M.Corresponding author
Institute Medical Champel, 1206, champel, Geneva, Switzerland
Glandular-cystic bladder cystitis is a rare, benign non-tumor condition, preferentially located on the area of the bladder trigone and can simulate a malignant tumor. It is a benign reactive metaplasia of the bladder submucosa, characterized by hyperplasia of the islets of Von Brunn and cystic. It is classified among reactive epithelial anomalies of the urothelium, such as islet hyperplasia of Von Brünn, cystitis, glandular cystitis, nephrogenic metaplasia and epidermoid metaplasia. It presents a clinical diagnostic challenge having the expression of a simple recurrent cystitis and misleading the radiological diagnosis evoking a malignant tumor of the bladder. Its certainty diagnosis is histological. We report the case of a 38-year-old young man who consulted for recurrent cystitis. The CT scan showed a vegetative tissue structure of the middle and left medial vesical floor, sawtooth 3 cm long axis suspecting a tumor of the bladder. The patient underwent transurethral resection of the bladder lesion. The histological and immunohistochemical examination concluded with glandular and cystic cystitis (minor form). In the light of this observation, we will discuss the diagnostic difficulties, the pathophysiological mechanisms, the radiological aspects, the anatomopathological, therapeutic features and the prognosis of this rare condition. The literature regarding this entity has been reviewed and the differential diagnosis was discussed.
Jul 2017 DOI 10.14302/issn.2574-4372.jesr-17-1705
Varma VijayalakshmiCorresponding author
Biomarkers and Alternative Models Branch, Division of Systems Biology, National Center for Toxicological Studies, Jefferson, AR
Drug-induced cardiotoxicity is one of the predominant reasons for drug attrition and withdrawals. This is of critical concern when potentially cardiotoxic drugs are administered to individuals with inherited arrhythmogenic cardiac diseases or with metabolic diseases such as obesity and diabetes, which are key risk factors for cardiovascular diseases. Pathophysiological alteration prevalent under such conditions can alter or exacerbate cardiotoxic responses. The growing incidence of obesity, diabetes and metabolic syndrome subject a significant percentage of the population to drug treatments, thereby augmenting their risk for drug-induced cardiovascular toxicity. Hence, screening for drug-induced cardiotoxicity early in the preclinical stages of drug development, by using appropriate human disease models, can be effective in ensuring safety in clinical trials and preventing late stage and post-marketing drug withdrawals owing to cardiotoxicity. The advent of human pluripotent stem cells (hPSC) and induced pluripotent stem cell (iPSC)-derived cardiomyocytes are revolutionizing safety/toxicity screening in human cells by providing relevant human-specific, renewable model systems to explore human drug toxicity. The ability to generate patient-specific iPSCs that can model cardiac diseases, now offers a valuable option that can further improve drug safety assessments and enable a more accurate prediction of toxicity that occurs in the representative population that are prescribed the drugs. Use of appropriate disease models will not only provide cost savings by decreasing potential drug attrition and withdrawals, seen with many drugs, but will also be a promising option to advance precision medicine
May 2015 DOI 10.14302/issn.2470-5020.jnrt-14-520
Li Hai-fengCorresponding author
Department of Neurology, Qilu Hospital of Shandong University, Jinan, China
This article has been retracted on November 20, 2015. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2470-5020.jnrt-25-5846) In-stent thrombosis (IST) is a complication of angioplasty and stenting, especially in the vessels with smaller diameter. We present a case of subacute IST after stenting treatment of an isolated higher stenosis of the right middle cerebral artery (MCA). Analysis of clinical features and emergent brain image helped to indicate the pathophysiological mechanism underlining the symptoms of this patient. Emergent Transcranial Doppler (TCD) helped to evaluate the compensatory collateral circulation and provided good supporting evidence in deducing the mechanism of IST. Slightly larger size of the implanted stent that caused dissection or vascular endothelium injury was presumed in this patient. Persistent evidence of inflammatory factors might also contribute to IST in this patient.
Jan 2015 DOI 10.14302/issn.2372-6601.jhor-14-377
Zaidah A WCorresponding author
Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia,Kubang Kerian, Malaysia.
Background Abnormalities of plasma von Willebrand Factor (vWF) system has been described in solid tumors but more information is required to understand the pathophysiological process in haematological malignancies. Objectives This study was carried out to investigate the changes in vWF-related parameters including ADAMTS13 protein level in aggressive haematological malignancies and to identify the prevalence of anti-ADAMTS13 antibody as well as its correlations with vWF-related parameters. Patients/Methods Patient newly diagnosed or having relapse acute leukaemias or aggresive non-Hodgkin lymphomas were recruited into this study. Exclusion criterias include; pregnancy, patient already commenced chemotherapy, sepsis or has background congenital bleeding disorders. Blood specimen was subjected to; blood counts, ADAMTS13 protein, ADAMTS13 antibody detection, vWF:Ag, vWF activity, factor VIII level (FVIII) and vWF: CBA (collagen binding assays) Results and Conclusion A total of 60 subjects with median age at 42.5 (IQR: 23.25-57.5) were included. There were 34(56.7%) lymphomas and 26(43%) acute leukaemias. FVIII, vWF:Ag, wVF activity and vWF:CBA level were elevated whereas ADAMTS13 protein was reduced in majority of patients. Those with lymphomas showed significantly higher levels of FVIII, vWF:Ag, vWF:activity and vWF:CBA compared to the leukaemias. 38(63.3%) of patients showed presence of ADAMTS 13 autoantibody. There was however no correlation between ADAMTS13 protein and vWF-related parameters or with ADAMTS13 autoantibodies. There was a high prevalence of ADAMTS 13 autoantibodies in this cohort despite the absence of thrombotic thrombocytopenic purpura (TTP). The more pronounced changes in vWF-related parameters among aggressive lymphomas compared to acute leukaemias are in tandem with the marginally higher rates of venous thromboembolism in the former.