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The Journal of Pediatrics May 2024To assess the efficacy of valganciclovir in infants with hearing loss and clinically inapparent congenital cytomegalovirus infection (cCMV), as there is no consensus on...
OBJECTIVE
To assess the efficacy of valganciclovir in infants with hearing loss and clinically inapparent congenital cytomegalovirus infection (cCMV), as there is no consensus on treatment of this group.
STUDY DESIGN
A nationwide, nonrandomized controlled trial, comparing 6 weeks of oral valganciclovir to no treatment in infants with cCMV, recruited after newborn hearing screening resulted in referral to an audiologist. The choice whether to treat was left to parents of subjects. Eligible subjects were full term infants aged <13 weeks with sensorineural hearing loss and diagnosed with cCMV through dried blood spot testing. The primary outcome, measured by linear and ordinal logistic regression, was change in best-ear hearing from baseline to follow-up at 18-22 months of age.
RESULTS
Thirty-seven participants were included in the final analysis, of whom 25 were in the treatment group and 12 in the control group. The majority of subjects in both groups had neuroimaging abnormalities, which were mostly mild. Hearing deterioration was more likely in the control group compared with the treatment group (common OR 0.10, 95% CI 0.02-0.45, P = .003). Mean best-ear hearing deteriorated by 13.7 dB in the control group, compared with improvement of 3.3 dB in the treatment group (difference 17 dB, 95% CI 2.6 - 31.4, P = .02).
CONCLUSIONS
We investigated treatment in children with hearing loss and clinically inapparent cCMV. Although our study was nonrandomized, it is the first prospective and controlled trial in this population. Valganciclovir-treated children with hearing loss and inapparent cCMV had less hearing deterioration at 18 through 22 months of age than control subjects.
EUDRACT REGISTRY NUMBER
2013-003068-30.
Topics: Humans; Valganciclovir; Cytomegalovirus Infections; Antiviral Agents; Male; Female; Infant; Infant, Newborn; Hearing Loss, Sensorineural; Treatment Outcome; Ganciclovir; Neonatal Screening; Prospective Studies; Follow-Up Studies; Administration, Oral
PubMed: 38336204
DOI: 10.1016/j.jpeds.2024.113945 -
Investigative Ophthalmology & Visual... Nov 2023The objective of this study was to explore the ocular and systemic outcomes of herpes simplex virus type 1 (HSV-1) infection in guinea pigs, to monitor the spontaneous...
PURPOSE
The objective of this study was to explore the ocular and systemic outcomes of herpes simplex virus type 1 (HSV-1) infection in guinea pigs, to monitor the spontaneous reactivation of the virus, and to assess the effectiveness of various treatments, drawing comparisons to conventional rabbit models.
METHODS
Guinea pigs and rabbits were infected in the right corneas with differing doses and strains of HSV-1. Observations were made over a 71-day period, focusing on comparing ocular lesions, viral shedding patterns, and weight loss between the two animal models. Postinfection, the effectiveness of trifluridine ophthalmic drops, oral acyclovir, and valacyclovir was evaluated. The confirmation of viral infection was done through virus titer assay, fluorescein staining, and corneal imaging.
RESULTS
Guinea pigs and rabbits manifested symptoms akin to human herpes stromal keratitis (HSK) when exposed to varying titers of viral suspension. Regardless of the initial viral load, all guinea pig groups demonstrated comparable ocular pathology, witnessing conditions like blepharitis and conjunctivitis within 3 days, progressing to severe conditions, including total corneal opacification and necrotizing keratitis. Tear film collection revealed nonsignificant differences in viral plaques between all groups. Notably, guinea pigs in the low-infection group experienced the most weight loss, although without significant differences. The replication of the same experiment on rabbits yielded consistent results in disease pathology across different groups, with occurrences of blepharitis and conjunctivitis. Interestingly, after initial resolution, guinea pigs presented a more frequent and broadly observed increase in disease score and corneal opacity, a phenomenon rarely seen in rabbits within the same timeframe. The effectiveness of 1% trifluridine was observed in mitigating ocular HSV-1 disease in both species, whereas oral acyclovir and valacyclovir were found to be detrimental and ineffective in guinea pigs but not in rabbits.
CONCLUSIONS
This study demonstrates the potential suitability of guinea pigs as new models for ocular HSV-1 investigations, filling a critical preclinical void of models capable of showcasing spontaneous HSV reactivation in the eye. The observed similarities and differences in the reactions of guinea pigs and rabbits to HSV-1 infection and treatments provide crucial insights, laying the foundation for future studies on ocular HSV pathogenesis, latency, and improved treatment options.
Topics: Animals; Guinea Pigs; Humans; Rabbits; Acyclovir; Blepharitis; Conjunctivitis; Cornea; Herpes Simplex; Herpesvirus 1, Human; Trifluridine; Valacyclovir; Weight Loss; Antiviral Agents
PubMed: 38015175
DOI: 10.1167/iovs.64.14.41 -
Viruses May 2024Epidemiological studies have shown that HPV-related diseases are the most prevalent sexually transmitted infections. In this context, this report will present various... (Review)
Review
Epidemiological studies have shown that HPV-related diseases are the most prevalent sexually transmitted infections. In this context, this report will present various clinical cases demonstrating the effectiveness of Acyclovir (ACV) or its prodrug Valaciclovir (VCV), both acyclic guanosine analogs commonly used for the treatment of HHV-1 and HHV-2, for the treatment of HPV-related diseases. The report shows the remission of five cases of penile condyloma and a case of remission in a woman affected by cervical and vaginal condylomas and a vulvar giant condyloma acuminate of Buschke and Lowenstein. The literature review shows that ACV is effective in treating skin warts when administered orally, topically, and intralesionally, suggesting its therapeutic potential in other diseases associated with HPV. ACV was also used successfully as an adjuvant therapy for juvenile and adult forms of laryngeal papillomatosis, also known as recurrent respiratory papillomatosis, prolonging the patient's symptom-free periods. Although the prevention of HPV infections is certainly achieved with the HPV vaccine, ACV and VCV have shown to be effective even against genotypes not included in the current vaccine and can be helpful for those problematic clinical cases involving unvaccinated individuals, immunocompromised patients, people who live with HIV, or non-responders to the vaccine. We and others concluded that randomized clinical trials are necessary to determine the efficacy of ACV and VCV for HPV-related diseases.
Topics: Adult; Female; Humans; Male; Acyclovir; Antiviral Agents; Papillomavirus Infections; Treatment Outcome; Valacyclovir
PubMed: 38793636
DOI: 10.3390/v16050756 -
Journal of Ophthalmic Inflammation and... Feb 2024To report a case of primary vitreoretinal lymphoma masquerading as infectious retinitis that was diagnosed via a retinal biopsy.
PURPOSE
To report a case of primary vitreoretinal lymphoma masquerading as infectious retinitis that was diagnosed via a retinal biopsy.
OBSERVATIONS
A 72-year-old female patient was referred to our ophthalmology clinic for evaluation of retinitis and vasculitis in the right eye (OD). On examination, best-corrected visual acuities (BCVAs) were hand motions OD and 20/20 in the left eye (OS). Fundus examination revealed optic disc edema and diffuse retinal whitening superior to the superotemporal arcade OD. Given the high suspicion of infectious retinitis, the patient was treated with intravitreal foscarnet, systemic acyclovir, and oral prednisone and underwent a comprehensive uveitis workup, which was unremarkable for viral and autoimmune entities. Given the patient's history of diffuse large B cell lymphoma with cutaneous involvement, vitreoretinal lymphoma was suspected, prompting pars plana vitrectomy with a retinal biopsy. Biopsy and immunohistochemistry results were consistent with B-cell lymphoma, and the patient was treated with high-dose methotrexate and rituximab. At 5-month follow-up, BCVAs were hand motions OD and 20/30 OS, and fundus examination demonstrated disc edema with resolution of retinal whitening OD. She responded well to the treatment with regression of vitreoretinal lymphoma on examination and is being monitored closely for lymphoma recurrence.
CONCLUSIONS AND IMPORTANCE
Although uncommon, patients with vitreoretinal lymphoma may masquerade as infectious retinitis, and vitreoretinal lymphoma should be suspected when refractory to antiviral therapy and in the setting of a negative workup for viral etiologies. Vitrectomy with retinal biopsy may be considered to aid the diagnosis of vitreoretinal lymphoma although careful consideration of the risks and benefits is warranted.
PubMed: 38324143
DOI: 10.1186/s12348-024-00389-y -
Internal Medicine (Tokyo, Japan) Aug 2023Pregnancy is a known risk factor for amebic enteritis, which develops into potentially fatal fulminant amebic enteritis in some cases. We describe a case of a...
Pregnancy is a known risk factor for amebic enteritis, which develops into potentially fatal fulminant amebic enteritis in some cases. We describe a case of a 27-year-old non-immunosuppressed pregnant woman with fulminant amebic enteritis complicated with cytomegalovirus enteritis. She improved with intensive care and intravenous metronidazole and ganciclovir but eventually required subtotal colectomy for intestinal stenosis. It is difficult to diagnose amebic enteritis, especially in a non-endemic area. Amebic enteritis must be considered as a differential diagnosis for refractory diarrhea with bloody stools in women in the perinatal period, even those without immunosuppression.
Topics: Pregnancy; Humans; Female; Adult; Dysentery, Amebic; Metronidazole; Ganciclovir; Risk Factors; Enteritis
PubMed: 36575014
DOI: 10.2169/internalmedicine.0839-22 -
Cancer Science Aug 2023Immune cells can recognize tumor-associated antigens released from dead tumor cells, which elicit immune responses, potentially resulting in tumor regression. Tumor cell...
Immune cells can recognize tumor-associated antigens released from dead tumor cells, which elicit immune responses, potentially resulting in tumor regression. Tumor cell death induced by chemotherapy has also been reported to activate immunity. However, various studies have reported drug-induced immunosuppression or suppression of inflammation by apoptotic cells. Thus, this study aimed to investigate whether apoptotic tumor cells trigger antitumor immunity independent of anticancer treatment. Local immune responses were evaluated after direct induction of tumor cell apoptosis using a Herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system. The inflammatory response was significantly altered at the tumor site after apoptosis induction. The expression of cytokines and molecules that activate and suppress inflammation simultaneously increased. The HSV-tk/GCV-induced tumor cell apoptosis resulted in tumor growth suppression and promoted T lymphocyte infiltration into tumors. Therefore, the role of T cells after inducing tumor cell death was explored. CD8 T cell depletion abrogated the antitumor efficacy of apoptosis induction, indicating that tumor regression was mainly dependent on CD8 T cells. Furthermore, CD4 T cell depletion inhibited tumor growth, suggesting the potential role of CD4 T cells in suppressive tumor immunity. Tumor tissues were evaluated after tumor cell apoptosis and CD4 T cell depletion to elucidate this immunological mechanism. Foxp3 and CTLA4, regulatory T-cell markers, decreased. Furthermore, arginase 1, an immune-suppressive mediator induced by myeloid cells, was significantly downregulated. These findings indicate that tumors accelerate CD8 T cell-dependent antitumor immunity and CD4 T cell-mediated suppressive immunity. These findings could be a therapeutic target for immunotherapy in combination with cytotoxic chemotherapy.
Topics: Humans; Ganciclovir; Thymidine Kinase; Simplexvirus; Genetic Therapy; Apoptosis; Neoplasms; CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Inflammation; Antiviral Agents
PubMed: 37322820
DOI: 10.1111/cas.15843 -
American Journal of Ophthalmology Case... Dec 2023To describe a case of retinal and optic nerve metastases masquerading as acute retinal necrosis secondary to primary squamous cell carcinoma of the lung.
PURPOSE
To describe a case of retinal and optic nerve metastases masquerading as acute retinal necrosis secondary to primary squamous cell carcinoma of the lung.
OBSERVATIONS
A 66-year-old male with a history of Stage IV lung cancer, actively on chemotherapy, presented with right eye vision loss, an afferent pupillary defect, and partial visual field deficiencies. Exam revealed vitritis, macula-involving infiltrative retinitis, optic neuritis, and vasculitis of the right eye. The patient was treated empirically for acute viral retinitis with intravitreal foscarnet and ganciclovir injections and oral acyclovir and trimethoprim-sulfamethoxazole. A diagnostic pars plana vitrectomy with vitreous biopsy, intravitreal antivirals and silicone oil fill was performed. The resulting cytology was positive for malignant squamous cell carcinoma.
CONCLUSIONS AND IMPORTANCE
We present a unique case of primary squamous cell carcinoma metastasizing to the retina and optic nerve which masqueraded as an acute viral retinitis. To date, there have not been any reported cases on Pubmed or Google Scholar at publication time of known squamous cell carcinoma metastases to the retina that demonstrated interval growth leading to emergent elevations in intraocular pressure (IOP). This case demonstrates the importance of considering metastasis when encountering an atypical acute retinal necrosis case, as well as bring awareness to the possibility that elevated IOP may be the first sign of interval metastases, despite surgical debulking, in cases involving known tumor metastases to the retina.
PubMed: 37869266
DOI: 10.1016/j.ajoc.2023.101934 -
Heliyon Jan 2024This research paper reports enhancing Acyclovir's gastric residence time by implementing a raft-forming drug delivery system. Because acyclovir is a narrow absorption...
This research paper reports enhancing Acyclovir's gastric residence time by implementing a raft-forming drug delivery system. Because acyclovir is a narrow absorption window drug, it has a poor bioavailability of 10-20 % and a short half-life (t) of 2.5 h. The guar gum and GMS-based floating raft formulation retain the drug in the stomach for an extended period by enhancing GRT. The Box-Behnken design is used to optimize the amount of guar gum, glyceryl monostearate, and calcium carbonate and to study how they affect the in vitro gelation time, viscosity, and in vitro drug release. The ratio of drug and excipients in guar gum (1:0.5), GMS (1:1.25) based FRF suspension containing sodium citrate (0.25 %), carbopol (0.1 %), and calcium carbonate (1:1.5). Seventeen runs were developed through the Box-Behnken design to study all the optimal interactions between variables and responses through a polynomial equation. The optimized formulation is then characterized using various physicochemical tests such as rheological analysis, in vitro drug release, kinetic drug release, and in vitro permeation studies. The in vitro gelation time, viscosity, and in vitro drug release time of optimized FRF are 12 s, 1090 cps, and 88 % at 24 h, respectively. The flux and permeability coefficient of the optimized batch have a higher value indicating higher permeability of acyclovir. The FRF follows non-fickian diffusion as a drug release mechanism. The results show that the raft-forming drug delivery system significantly enhances the absorption of Acyclovir by prolonging drug release and also improving its gastric residence time in the stomach. This research contributes to the field of drug delivery systems by providing a novel approach for improving the therapeutic efficacy of acyclovir and potentially other drugs with similar characteristics.
PubMed: 38293518
DOI: 10.1016/j.heliyon.2024.e24301 -
Cureus Aug 2023Herpetic esophagitis (HE) is an esophageal infection caused by herpes simplex virus (HSV). Although less common, it can occasionally affect immunocompetent hosts. It can...
Herpetic esophagitis (HE) is an esophageal infection caused by herpes simplex virus (HSV). Although less common, it can occasionally affect immunocompetent hosts. It can manifest as odynophagia and/or dysphagia and should lead to an investigation by upper digestive endoscopy with a biopsy. The authors report a case of a 65-year-old man with a past medical history relevant for schizophrenia, oligophrenia, and malnutrition, and no other history or evidence of immunosuppression, who presented with severe dysphagia over weeks and recent episodes of food aspiration with consequent pneumonia. An upper gastrointestinal endoscopy was performed, revealing severe stenosis at the level of the gastroesophageal junction with scar tissue, not transposable with the endoscope. The biopsy led to the diagnosis of hepatic esophagitis. Despite the immunocompetent status (excepting only the risk factor malnutrition) and treatment with acyclovir, with initial clinical improvement, the patient died a few weeks after diagnosis after multiple respiratory complications such as nosocomial infection. This case highlights that herpetic esophagitis is sometimes observed in immunocompetent hosts. HE has a self-limited course, with severe complications more frequent in immunosuppressed patients. However, it is also important to suspect this condition in immunocompetent patients and look for risk factors, given the potential morbidity this disease entails. In this group of patients, the presence of predisposing factors and associated comorbidities, such as malnutrition, alcohol consumption, or use of corticosteroids, have been associated with the development of viral esophagitis (including HE). HE remains a clinical challenge, especially in patients with risk factors for immunosuppression, such as malnutrition, as in the reported case.
PubMed: 37736443
DOI: 10.7759/cureus.43858 -
The American Journal of Case Reports Feb 2024BACKGROUND Infectious keratitis after pterygium surgery is a rare but potentially devastating complication. The present study presents 5 cases of herpes simplex... (Review)
Review
BACKGROUND Infectious keratitis after pterygium surgery is a rare but potentially devastating complication. The present study presents 5 cases of herpes simplex keratitis (HSK) after pterygium surgery. CASE REPORT This study was conducted in our clinic in a 5-year period from February 2017 to September 2021. The 5 patients were men, aged between 42 and 73 years, with no prior history of herpes simplex virus (HSV) infections. Symptoms appeared near 1 month (median 30 days, range 10 to 70 days) after primary pterygium surgery. Diagnosis was based on clinical symptoms and laboratory test results, such as tear HSV-sIgA, corneal tissue polymerase chain reaction, and next-generation sequencing of metagenomics. The epithelial (1/5) and stromal (4/5) subtypes of HSK were identified. The patients received topical ganciclovir gel, immunosuppressive eyedrops, and oral acyclovir tablets, along with additional surgical interventions if necessary. Three were healed with conservative therapy, 1 eye required amniotic membrane transplantation due to corneal melt, and 1 was perforated and followed by corneal grafting. Finally, a literature review of previous publications on HSK after ocular surgeries was conducted. CONCLUSIONS HSK is a rare but serious complication that can arise after uneventful pterygium surgery. It is worthy of attention that both epithelial and stromal forms can occur. Timely diagnosis and treatment are crucial to prevent unfavorable outcomes. Consequently, routine corneal fluorescein staining, tear sIgA examination, and corneal scraping for polymerase chain reaction or next-generation sequencing of metagenomics should be performed in any suspected cases.
Topics: Male; Humans; Adult; Middle Aged; Aged; Female; Antiviral Agents; Pterygium; Keratitis, Herpetic; Acyclovir; Immunoglobulin A, Secretory
PubMed: 38400535
DOI: 10.12659/AJCR.942401