Ryzumvi: pioneering advances in countering drug-induced mydriasis.

This article discusses the prevalence and impact of pharmacologically-induced mydriasis, a condition where the pupil becomes excessively dilated due to certain drugs. It highlights the challenges faced by medical professionals in dealing with this condition and the limitations of current treatments, like pilocarpine and dapiprazole, which come with systemic side effects and specific contraindications, limiting their regular use. The article introduces Ryzumvi, a novel ophthalmic solution approved by the US FDA, which effectively reverses mydriasis caused by adrenergic agonists and antimuscarinic drugs. The article provides insights into its mechanism of action, clinical efficacy, pharmacokinetics, safety, and tolerance based on extensive clinical trials. It emphasizes its rapid onset of action and effectiveness in restoring pupils to their initial size. It also underlines the potential for expanded applications, including in pediatric patients, solidifying its importance in the field of ophthalmology. Furthermore, Ryzumvi represents a promising advancement in managing pharmacologically-induced mydriasis, offering swift and effective relief while highlighting the importance of adhering to safety precautions and the continuous research and development efforts in ophthalmology to comprehensively address vision-related disorders and enhance patient outcomes.

"Izervay (avacincaptad pegol): paving the way for vision preservation in geographic atrophy".

Age-related macular degeneration (AMD) is a progressive retinal disease that primarily affects the macula, leading to central vision loss and impaired color vision. Among its most severe forms is geographic atrophy (GA), which results in irreversible central blindness. While numerous risk factors, including age, smoking, and genetics, contribute to the development of AMD, effective treatment options for GA have been limited. This article centers on Izervay [avacincaptad pegol (ACP)], an FDA-approved drug designed to address the unmet medical needs of patients with GA secondary to AMD. The pathophysiology of GA involves oxidative damage, chronic inflammation, and cell death, primarily due to complement system dysregulation. Previous treatments for GA have shown limited efficacy, leaving patients searching for more effective solutions. Izervay, with its unique mechanism of action, inhibits complement protein C5, disrupting the formation of the membrane attack complex and slowing retinal cell degeneration. Clinical trials have demonstrated Izervay's ability to significantly reduce the growth of GA lesions, offering hope for improved outcomes. Additionally, the drug has exhibited a tolerable safety profile, with common side effects including conjunctival hemorrhage and increased intraocular pressure. Izervay represents a breakthrough in AMD treatment, offering the potential to preserve vision in those at risk of irreversible vision loss due to GA. While further research is necessary to evaluate long-term efficacy and accessibility, its approval opens new possibilities in AMD management, transforming the lives of individuals affected by this condition.

Japanese encephlu emergence in Australia: the potential population at risk.

Japanese encephalitis virus (JEV), an RNA virus transmitted by Culex mosquitoes, primarily cycles between aquatic birds and mosquitoes with pigs as amplifying hosts, posing a significant global encephalitis threat. The emergence and spread of the JEV in new epidemiological regions, such as recent cases in Australia and nonendemic areas like Pune, India, raise significant concerns. With an estimated 68 000 clinical cases and 13 600 to 20 400 deaths annually, JEV poses a substantial global health threat. The virus primarily affects children, with a case-fatality ratio of 20-30% and long-term neurological sequelae in survivors. The changing epidemiology, influenced by factors like bird migration, climate change, and increased urbanization, contributes to the geographic expansion of JEV. The recent outbreaks underscore the potential for the virus to establish itself in nonendemic regions, posing a threat to populations previously considered at low-risk. With limited treatment options and high rates of neurological complications, continued surveillance, traveler vaccination, and research into treatments are crucial to mitigate the impact of JEV on human health. The evolving scenario necessitates proactive measures to prevent and control the spread of the virus in both endemic and newly affected areas.

Neurological complications of influenza vaccination: navigating the spectrum with a focus on acute disseminated encephalomyelitis (ADEM).

Introduction: Acute disseminated encephalomyelitis (ADEM) is a rare neurological disorder characterized by inflammation in the brain and spinal cord. This systematic review aims to investigate the potential association between ADEM and influenza vaccination by analyzing relevant case reports. ADEM is traditionally thought to be a monophasic condition, predominantly affecting children, often following viral illnesses or immunizations. Recent attention has focused on a possible link between ADEM and influenza vaccination, prompting the need for a thorough investigation. Methods: The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the AMSTAR2 (A MeaSurement Tool to Assess systematic Reviews 2) guidelines. Electronic searches were conducted on PubMed, Cochrane Library, and clinicaltrials.gov databases, spanning up to August 2023. Inclusion criteria encompassed full-text articles in English, observational studies, case reports, and case series providing comprehensive details for confirming clinical diagnoses of ADEM following influenza vaccination. Data were extracted, including demographic information, vaccination details, clinical symptoms, diagnostic evaluations, treatment modalities, and outcomes. Quality assessment was performed using the Joanna Briggs Institute (JBI) Critical Appraisal tool. Results: A total of 23 cases of ADEM following influenza vaccination were identified from 19 included articles. The mean age of affected individuals was 40.2 years (±25.7) with 60.8% being male. Common presenting symptoms included muscle weakness (52.1%), urinary abnormalities (30.4%), altered consciousness (26%), and sensory disturbances (26%). Neurological examination revealed findings such as extensor plantar reflex (positive Babinski sign) in 26%, hyperreflexia in 30.4%, and generalized hyporeflexia in 13% of the cases. Diagnostic evaluations involved MRI, showing multiple hyperintense lesions in cerebral hemispheres (43.4%), subcortex (60.8%), and spinal cord (39.1%). Cerebrospinal fluid analysis indicated elevated white blood cell count in 69.5% of cases, with lymphocytic pleocytosis in 52.1%. Oligoclonal bands were reported positively in 8.6% of cases. Treatment approaches varied, with intravenous methylprednisolone being the most common (39.1%). Out of the 23 cases, two (8.6%) patients had a fatal outcome, while the rest showed clinical improvement with complete or partial resolution of symptoms. Persisting symptoms included numbness in the lower extremities (8.6%) and impaired ability to walk after 10 months (4.3%). Conclusion: While the association between ADEM and influenza vaccination is rare, healthcare professionals should remain vigilant and consider patients' vaccination history, particularly following an influenza immunization. This systematic review highlights the clinical manifestations, diagnostic tools, treatment approaches, and outcomes of ADEM cases post-influenza vaccination. Further research is essential to understand this association and improve clinical decision-making, ensuring the safety and efficacy of immunization programs.

Intracranial intricacies: Comprehensive analysis of rare skull base meningiomas-A single-center case series.

This study paper's main goal is to report rare cases of skull base meningiomas that exemplify the complexities of diagnosis, therapy, and postoperative care. By describing these rare cases, we hope to advance knowledge of the clinical signs, difficulties, and prognoses of skull base meningiomas in a challenging anatomical setting. In the posterior cranial fossa, our investigation reveals a unique example of skull base meningioma that involved numerous cranial nerves and complex vasculature. A variety of visual abnormalities were present in the patient's clinical presentations, highlighting the wide range of symptoms that these tumors might cause depending on their precise positions. These cases highlight the critical importance of preoperative imaging, including high-resolution MRI and angiography, as well as the diagnostic difficulties these tumors pertain. By reporting these instances, our research adds to the body of knowledge about skull base meningiomas and offers insightful information about the nuances of their therapies. Our findings highlight the importance of individualized treatment plans, interdisciplinary cooperation, and the demand for continued study to better comprehend these convoluted tumors. Such studies are essential for advancing our knowledge of these enigmatic tumors, guiding clinical judgment, and eventually improving patient outcomes. These findings are important because they can fill information gaps, improve treatment plans, and encourage additional research in neuro-oncology. Abstract: This study presents a series of three rare cases of skull base meningiomas, emphasizing the complexities in diagnosis, treatment, and postoperative care. The patients' clinical presentations and imaging highlighted the diverse symptoms and challenges associated with these tumors, found in intricate anatomical locations. The cases underscore the crucial role of preoperative high-resolution imaging and angiography in diagnostic accuracy. Surgical intervention, guided by a multidisciplinary approach, is pivotal in managing these demanding cases. Histopathological examinations confirmed atypical meningiomas. The postoperative phases involved meticulous care to ensure optimal recovery and functional outcomes. Our findings contribute to the understanding of skull base meningiomas, emphasizing the need for personalized treatment plans and ongoing research to improve patient outcomes in neuro-oncology.

Revolutionary breakthrough: FDA approves Vyjuvek, the first topical gene therapy for dystrophic epidermolysis bullosa.

This article provides an updated overview of Vyjuvek, a Food and Drug Administration (FDA) approved medication and its potential in managing dystrophic epidermolysis bullosa (DEB). DEB is a rare genetic disorder characterized by skin fragility, blistering, wounds, and scarring. The underlying cause of DEB is the impaired production of type VII collagen (COL7), leading to weakened anchoring fibrils in the skin. Vyjuvek is the first topical gene therapy for DEB, utilizing a genetically modified HSV-1 (herpes simplex virus 1) vector to express human COL7 and promote wound healing. Clinical trials have shown that Vyjuvek increases the probability of complete wound healing compared to placebo. Although further research is needed, Vyjuvek represents a significant advancement in addressing the unmet medical needs of patients with DEB, offering hope for improved quality of life and long-term complication reduction.

Elrexfio™ (elranatamab-bcmm): The game-changer in treatment of multiple myeloma.

Multiple myeloma is the second most common plasma cell malignancy, characterized by uncontrolled proliferation of plasma cells within the bone marrow. ELREXFIO™ (elranatamab-bcmm) is a recently FDA-approved drug for relapsed and refractory multiple myeloma. The progression of multiple myeloma involves interactions with various bone marrow cell types, and targeting this microenvironment has shown promising results in inhibiting its growth and osteolysis. ELREXFIO, a bispecific antibody targeting CD3 and BCMA, activates cytotoxic T-lymphocyte responses against BCMA-expressing myeloma cells. Clinical trials, such as MagnetisMM-3, demonstrated significant response rates and long-term tolerability. Its approval offers hope to multiple myeloma patients, especially those with relapsed or refractory cases, as innovative therapies like ELREXFIO continue to improve outcomes in this challenging malignancy.

Analysis of antidiabetic, antiulcer and analgesic potential of traditional ethnomedicinal plant Emex spinosa (L.) Campd. from Azad Jammu and Kashmir.

In this research antidiabetic, analgesic and antiulcer potential of traditional ethnomedicinal plant: Emex spinosa (L.) Campd. (Family Polygonaceae) was evaluated by extracting its phytoconstituents using methanol (MeOH) solvent through maceration protocol. The quantitative phytochemical analysis of the extract revealed flavonoids were highest in leaf extract (15.63±0.93 mg/mL) and with (11.5±0.57 mg/mL) in stem. Alkaloids and tanins were also present in the samples in various conc. while saponins were absent. To confirm pharmaceutical potential of plant against ulcer, diabetes and analgesic infirmities, a model experimental animal wistar albino rats (Rattus norvegicus) were used. In antiulcer study, using hot plate method the maximum results were observed with 250 mg/kg in the 2.5 hours of study. The leaf extract showed a 40.41±2.73 latency time and the fruit with a 36.77±2.41, and the stem with a 27.85±3.09, which was comparable to the standard drug Aspirin, i.e., 47.5±0.57. For analysis of antiulcer potential of the plants parts doses of 250 and 500 mg/kg was applied to check the reclamation of ethanol-induced acute ulcer and of Aspirin-induced chronic ulcer of stomach. In order to confirm efficacy of the drug potential of plant following parameters like microscopic evaluation, gastric volume, total acidity, mucosa weight, ulcer index, pH and histopathology of stomach were analyzed. In antidiabetic analysis, in an acute study after a single dose of 500 mg/kg extract after 2hrs the blood glucose levels were 367±51.09958NS, 416±59.79548NS, 437.5±61.96437NS mg/dL for leaf, stem and fruit, respectively. After4hrs 351.75±88.27644NS mg/dl, 448.25±25.64948NS mg/dl, 445.25±27.07205NS mg/dl and after 6hrs 354.5±92.70428NS, 442±24.60691NS, a440±33.16625NS mg/dl, respectively. The analgesic activity was explored by applying hot plate, tail flick and formalin paw licking method. In hot plate method the maximum results were observed with 250mg/kg in the 2.5 hours of study. The leaf extract showed a 40.41±2.73 latency time and the fruit with a 36.77±2.41 and the stem with a 27.85±3.09, which was comparable to the standard drug Aspirin, i.e., 47.5±0.57. The respective plant extracts at 250mg/kg showed a gradual rise in latency time when compared to the control. It was concluded that all three components of E. spinosa perform proved to be significant as potential source of herbal medicines to cure different prevalently occurring diseases. Furthermore, it was confirmed through results analysis that plant t can be used to discover novel drug using dedicated high throughput techniques and ethnopharmacological approaches.

Koolen-de Vries syndrome associated with continuous spike-wave in sleep

Koolen-de Vries syndrome (KdVS) is a genetic condition caused by 17q21.31 microdeletions or pathogenic variants in KANSL1. Affected patients most commonly exhibit some or all of the following: neonatal hypotonia, developmental impairment, facial dysmorphic features, and congenital malformations. Epilepsy occurs in approximately half, often with phenotypes on the epilepsyaphasia spectrum. We describe six children with KdVS found to have continuous spike-wave in sleep (CSWS) on EEG, four of whom were diagnosed with epileptic encephalopathy with CSWS and two with Landau-Kleffner syndrome. When compared with other children with CSWS on EEG, patients with KdVS may present at slightly later ages and with a longer interval between seizure diagnosis and identification of CSWS. There is no clear best treatment for children with CSWS, but two patients in our cohort were trialed on a variation of the ketogenic diet, and both reported clinical improvement. In one of the patients, the response was dramatic, and CSWS recurred when weaning of the ketogenic diet was attempted. Based on our findings, an EEG capturing a prolonged period of sleep should be arranged in any child with KdVS presenting with developmental regression or plateau, particularly if they have a preceding history of seizures.

The spectrum of indomethacin-responsive headaches in children and adolescents.

BACKGROUND: Headaches with marked, specific response to indomethacin occur in children, but the phenotypic spectrum of this phenomenon has not been well-studied. METHODS: We reviewed pediatric patients with headache showing ≥80% improvement with indomethacin, from seven academic medical centers. RESULTS: We included 32 pediatric patients (16 females). Mean headache onset age was 10.9 y (range 2-16 y). Headache syndromes included hemicrania continua (n = 13), paroxysmal hemicrania (n = 10), primary stabbing headache (n = 2), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (n = 1), primary exercise headache (n = 1) and primary cough headache (n = 1). Adverse events were reported in 13, most commonly gastrointestinal symptoms, which often improved with co-administration of gastro-protective agents. CONCLUSION: Indomethacin-responsive headaches occur in children and adolescents, and include headache syndromes, such as primary cough headache, previously thought to present only in adulthood. The incidence of adverse events is high, and patients must be co-treated with a gastroprotective agent.

Hypersensitivity Pneumonitis in a Pediatric Patient.

Hypersensitivity pneumonitis (HP) is a rarely diagnosed interstitial lung disease with variable manifestations. It results from repeated inhalation of certain antigens, e.g. mold, avian antigen, etc. in susceptible patients. The diagnosis is made by exposure history, relevant clinical presentation, and specific radiologic features. It is treated by avoidance of triggers and use of corticosteroids. We report a 7.5-year girl with HP. She was admitted for cough and severe respiratory distress. Key Words: Hypersensitivity pneumonitis, Antigen, Allergy, Child.

Seizures in Sotos syndrome: Phenotyping in 49 patients.

We aimed to describe the phenotypic spectrum of seizures in Sotos syndrome, a genetic condition involving overgrowth, macrocephaly, dysmorphic features, and learning disability, in which 60%-90% have NSD1 pathogenic variants. Patients were recruited from clinics and referral from support groups. Those with seizures and a clinical diagnosis of Sotos syndrome were included. Phenotyping data were collected via structured clinical interview and chart review. Forty-nine patients were included. Twenty had NSD1 testing results available; of these, 15 (75%) had NSD1 pathogenic variants. Seizure onset age ranged from 3 months to 12 years. Staring spells (absence or focal impaired awareness seizure) were the most frequently reported semiology (33/49; 67%), followed by febrile seizures (25/49; 51%) and afebrile bilateral tonic-clonic seizures (25/49; 51%). Most patients (33/49; 67%) had multiple seizure types. The majority (33/49; 67%) had seizures controlled on a single antiseizure medication or no medication. Nine (18%) had drug-resistant epilepsy. Epilepsy syndromes included febrile seizures plus, Lennox-Gastaut syndrome, childhood absence epilepsy, and generalized tonic-clonic seizures alone. The seizure phenotype in Sotos syndrome most commonly involves staring spells, afebrile tonic-clonic seizures or febrile convulsions; however, other seizure types may occur. Seizures are typically well-controlled with medication, but drug-resistant epilepsy occurs in a minority.

Focal Segmental Glomerulosclerosis in Paediatric Population of South Punjab Pakistan: A Tertiary Care Hospital Experience.

OBJECTIVES: To find out frequency, clinicopathological features, response of treatment and outcome among children with primary focal segmental glomerulosclerosis (FSGS). METHODS: This retrospective, non-interventional medical charts review study was conducted from a period of January 2011 to January 2020 at Pediatric Department of Nishtar Medical University Hospital, Multan, Pakistan. During the nine years study period, children of both genders, aged less than 16 years, with renal biopsies proven FSGS were included. Patient's demographic along with clinical and laboratory data, urine dipstick for proteinuria, renal functions, 24 hours urinary protein and ultrasonography findings of kidneys, ureters and bladder (KUB) were noted from case records. Response rates of various treatment options and their outcome like remission, partial remission, no remission with stable kidney disease & no remission with progression of kidney disease were noted. RESULTS: During the study duration, out of 307 renal biopsies performed in glomerulonephritis cases, 124 (40.4%) had primary FSGS. In 124 primary FSGS cases, mean age was 8.83±3.05 years while most of the children, 70 (56.5%) were above 10 years of age. Majority of the cases, 64 (51.6%) were male. Mean follow up duration was noted to be 28.35+18.47 months. Most of the cases, 68 (54.8%) were found to have complete remission, 22 (17.7%) partial remission while 11 (8.9%) progressed to ESKD. CONCLUSIONS: Among children, frequency of primary FSGS was high at our setting. Most of the cases achieved sustained remission rates with the help of immunosuppressive drugs. Cyclosporine and tacrolimus were found to be the most effective drugs.

Clinical correlation and prognostic significance of immunofluorescence in renal biopsies of patients having Glomerulonephritis.

OBJECTIVE: To correlate the immunofluorescence (IF) findings on renal biopsies of patients of glomerulonephritis (GN) with the clinical course of the disease. METHODS: This retrospective descriptive study was done at the Department of Pediatrics Medicine Unit-I, Nishtar Hospital Multan, from January 2008 to January 2019. A total of 387 cases of both gender, aged up to 16 years, diagnosed having GN on the basis of renal biopsies by light microscopy (LM) and IF findings, were included. Outcome as remission, partial remission, no remission with stable kidney disease, no remission with progressive kidney disease and end-stage kidney disease (ESKD) were computed. Chi square test was applied to see the correlation of IF findings and outcome by taking p value less than 0.05 as statistically significant. RESULTS: Focal segmental glomerulosclerosis (FSGS) was found to be the commonest histopathology finding noted in 158 (40.8%) followed by mesangioproliferative GN 74 (19.1%) and membranous nephropathy 42 (10.9%). Complete remission was observed in 145 (37.5%) cases whereas ESKD was seen in 26 (6.7%). Distinct pattern of IF findings were shown when distribution of IF findings were seen with respect to all study variables (p value < 0.001). For outcome, 134 (51.3%) IF negative cases had complete remission while 93 (35.6%) negative IF findings also had partial remission. ESKD was seen among 14 (25.9%) IgM positive and three (33.3%) IgA positive cases. CONCLUSION: Immunofluorescence proved an important diagnostic tool in reaching the exact diagnosis in various types of GN. Distinct correlation between IF findings and clinical course of various types of GN was observed. IF negative cases had better outcome and was not having progressive course of disease so prognosis remained better than IF positive cases in this study.

Non-alcoholic steatohepatitis in liver transplant recipients diagnosed by serum cytokeratin 18 and transient elastography: A prospective study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) seem common after liver transplantation. AIM: To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients, namely controlled attenuation parameter (CAP) and the serum biomarker cytokeratin 18 (CK-18). We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology. METHODS: We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018. Serial measurements of CK-18 and CAP were recorded. NAFLD and NASH were diagnosed by CAP ≥ 270 dB/m, and a combination of CAP ≥ 270 dB/m with CK-18 > 130.5 U/L, respectively. Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards. RESULTS: Overall, 40 liver transplant recipients (mean age 57 years; 70% males) were included. During a median follow-up of 16.8 mo (interquartile range 15.6-18.0), 63.0% and 48.5% of patients developed NAFLD and NASH, respectively. On multivariable analysis, after adjusting for sex and alanine aminotransferase, body mass index was an independent predictor of development of NAFLD [adjusted hazard ratio (aHR): 1.21, 95% confidence interval (CI): 1.04-1.41; P = 0.01] and NASH (aHR: 1.26, 95%CI: 1.06-1.49; P < 0.01). Compared to liver histology, CAP had a 76% accuracy to diagnose NAFLD, while the accuracy of CAP plus CK-18 to diagnose NASH was 82%. CONCLUSION: NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo. Close follow-up and nutritional counselling should be planned in overweight patients.

Clinical utility of therapeutic drug monitoring of antiepileptic drugs: Systematic review.

OBJECTIVE: To systematically review and evaluate the available evidence supporting or refuting clinical use of therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) in patients with epilepsy. METHODS: We searched MEDLINE, Embase, BIOSIS, Cochrane, PubMed, Africa-Wide Information, Web of Science, and grey literature. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM vs non-TDM were included. Two reviewers independently extracted the data. The primary outcome was seizure control; adverse effects were considered as secondary outcomes. The PROSPERO ID of this systematic review's protocol is CRD42018089925. RESULTS: Sixteen studies were identified meeting eligibility requirements. Four randomized controlled trials (RCTs), 1 meta-analysis, and 11 quasiexperimental (QE) studies were included in the systematic review. Results from the analysis of RCTs showed no significant positive effect of TDM on seizure outcome (only 25% positive effect of phenytoin). However, some of the QE studies found that TDM was associated with better seizure control or lower rates of adverse effects. The existing evidence from various designs has shown various methodological implications, which warrants inconclusive results and highlights the requirement of more number of studies in this line. CONCLUSIONS: If optimally implemented, TDM may enhance clinical care, particularly for phenytoin and other AEDs with complex pharmacokinetics. However, the ideal method for implementation is unclear, and serum drug levels should be considered in context with patient-reported clinical data regarding seizure control and adverse events.

Salient distractors can induce saccade adaptation.

When saccadic eye movements consistently fail to land on their intended target, saccade accuracy is maintained by gradually adapting the movement size of successive saccades. The proposed error signal for saccade adaptation has been based on the distance between where the eye lands and the visual target (retinal error). We studied whether the error signal could alternatively be based on the distance between the predicted and actual locus of attention after the saccade. Unlike conventional adaptation experiments that surreptitiously displace the target once a saccade is initiated towards it, we instead attempted to draw attention away from the target by briefly presenting salient distractor images on one side of the target after the saccade. To test whether less salient, more predictable distractors would induce less adaptation, we separately used fixed random noise distractors. We found that both visual attention distractors were able to induce a small degree of downward saccade adaptation but significantly more to the more salient distractors. As in conventional adaptation experiments, upward adaptation was less effective and salient distractors did not significantly increase amplitudes. We conclude that the locus of attention after the saccade can act as an error signal for saccade adaptation.