Localized delivery of therapeutics impact laryngeal mechanics, local inflammatory response, and respiratory microbiome following upper airway intubation injury in swine.

BACKGROUND: Laryngeal injury associated with traumatic or prolonged intubation may lead to voice, swallow, and airway complications. The interplay between inflammation and microbial population shifts induced by intubation may relate to clinical outcomes. The objective of this study was to investigate laryngeal mechanics, tissue inflammatory response, and local microbiome changes with laryngotracheal injury and localized delivery of therapeutics via drug-eluting endotracheal tube. METHODS: A simulated traumatic intubation injury was created in Yorkshire crossbreed swine under direct laryngoscopy. Endotracheal tubes electrospun with roxadustat or valacyclovir- loaded polycaprolactone (PCL) fibers were placed in the injured airway for 3, 7, or 14 days (n = 3 per group/time and ETT type). Vocal fold stiffness was then evaluated with normal indentation and laryngeal tissue sections were histologically examined. Immunohistochemistry and inflammatory marker profiling were conducted to evaluate the inflammatory response associated with injury and ETT placement. Additionally, ETT biofilm formation was visualized using scanning electron microscopy and micro-computed tomography, while changes in the airway microbiome were profiled through 16S rRNA sequencing. RESULTS: Laryngeal tissue with roxadustat ETT placement had increasing localized stiffness outcomes over time and histological assessment indicated minimal epithelial ulceration and fibrosis, while inflammation remained severe across all timepoints. In contrast, vocal fold tissue with valacyclovir ETT placement showed no significant changes in stiffness over time; histological analysis presented a reduction in epithelial ulceration and inflammation scores along with increased fibrosis observed at 14 days. Immunohistochemistry revealed a decline in M1 and M2 macrophage markers over time for both ETT types. Among the cytokines, IL-8 levels differed significantly between the roxadustat and valacyclovir ETT groups, while no other cytokines showed statistically significant differences. Additionally, increased biofilm formation was observed in the coated ETTs with notable alterations in microbiota distinctive to each ETT type and across time. CONCLUSION: The injured and intubated airway resulted in increased laryngeal stiffness. Local inflammation and the type of therapeutic administered impacted the bacterial composition within the upper respiratory microbiome, which in turn mediated local tissue healing and recovery.

Diagnosis and management of a herpes nipple infection that resulted in neonatal HSV encephalitis.

We present a case of a primigravida in her 30s who had a caesarean delivery of dichorionic diamniotic twins at 33 weeks of gestation. Her postpartum course was complicated by a herpes simplex virus (HSV) infection of her nipple, found after her neonates were diagnosed with HSV encephalitis. She was evaluated at her 3-week postpartum visit and reported that her neonates were concurrently admitted to the neonatal intensive care unit with disseminated neonatal HSV-1. The patient and her partner were in a monogamous relationship with no known history of HSV. Physical examination demonstrated a vertical fissure on the face of her right nipple and a small cluster of vesicles on her left hand. PCR swabs of the lesions were positive for HSV-1 at both locations. The patient was started on oral valacyclovir 1000 mg two times per day, topical acyclovir ointment applied 4-6 times per day and mupirocin ointment applied 3 times per day to her breast with resolution of her breast lesions. She was able to continue expressing her breastmilk with the help of a pump and then resumed breastfeeding once her infection was cleared. Her infants recovered after prolonged parenteral antiviral therapy with age-appropriate development at follow-up.

Lower motor neuron facial palsy in a postnatal mother with COVID-19.

COVID-19 is caused by the novel SARS-CoV-2 and is a potentially fatal disease that is of great global public health concern. In addition to respiratory symptoms, neurological manifestations have been associated with COVID-19. This is attributed to the neurotropic nature of coronaviruses. The authors present a case of Bell's palsy associated with COVID-19 in a term primigravida.

Novel Application of Hot Melt Extrusion Technology for Preparation and Evaluation of Valacyclovir Hydrochloride Ocular Inserts.

The objective of this study was to investigate the processability of hot-melt extrusion (HME) to formulate ocular inserts of valacyclovir hydrochloride and evaluate the in vivo bioavailability of the formulation. To optimize the formulation of this drug, different physical mixtures of the polymers and plasticizer were prepared. The physical mixture was extruded through a co-rotating twin-screw extruder, and the obtained ocular inserts were cut with dimensions of 4 mm × 2 mm × 1 mm to enhance the formulation instillation in the eye. Ocular inserts were evaluated for drug content, weight variation, uniformity of thickness, in vitro drug release, and in vivo drug bioavailability. The ocular inserts were thermally characterized using differential scanning calorimetry (DSC). The attributes observed for the ocular inserts were within the target specifications. The ocular inserts of valacyclovir hydrochloride were successfully prepared using the HME. They provided sustained drug release along with enhanced drug permeation when compared with the eyedrop solution and dissolve completely in 8 h. Additionally, the obtained results demonstrated that the formulation of ocular inserts of valacyclovir hydrochloride using HME was reproducible, robust, and effective method.

Different dosages of valaciclovir for the treatment of herpes zoster in adults: A randomized clinical study.

WHAT IS KNOWN AND OBJECTIVE: The dosages of valaciclovir used for herpes zoster treatment recommended by Chinese pharmaceutical companies can differ considerably from those reported in the literature. This randomized clinical study compares the efficacy and safety of different oral valaciclovir doses for the treatment of herpes zoster in adults. METHODS: A total of 214 patients with herpes zoster were enrolled and randomized into two groups according to age: 98 patients in the 18-44-year group (younger patients) and 116 patients in the 45-74-year group (middle-aged and elderly patients). Patients in the two age groups were then prescribed different doses of valaciclovir. The high-dose group was administered 900 mg of valaciclovir, three times daily for 10 days, whereas the low-dose group was administered 300 mg of valaciclovir, two times daily for 10 days. The efficacy and side effects of these regimens were recorded on days 6, 11 and 30. RESULTS: In total, 207 (of 214 enrolled) patients completed the study. Of the seven patients who discontinued the study, five discontinued because their follow-up time was not fixed and two withdrew after moving to other cities. At the 11th day after treatment, the clinical effect of high-dose valaciclovir groups were significantly better than that of the low-dose valaciclovir groups in middle-aged and elderly patients (p < 0.05). The difference in visual analog scale (VAS) pain scores between the two dose groups was statistically significant in middle-aged and elderly patients at the 6th day(p < 0.05), whereas there was no difference in younger patients (p > 0.05). The VAS scores were significantly lower in high-dose group than in low-dose group at day 11 in both groups of patients(p < 0.05).There was no statistically significant difference in the time to skin scab improvement between the two different dose groups in younger patients (p > 0.05). Among middle-aged and elderly patients, the incidence of postherpetic neuralgia (PHN) was significantly lower in the high-dose group than in the low-dose group (p < 0.05). The difference in the incidence of adverse reactions between the high-dose and low-dose groups was not statistically significant (p > 0.05). Overall, the main side effect was headache. WHAT IS NEW AND CONCLUSION: The present study indicates that early treatment with high-dose valaciclovir can significantly reduce pain in patients, especially in elderly patients, in whom it can also reduce the incidence of PHN. In terms of safety, no significant difference was noted in the incidence of adverse reactions between high- and low-dose groups.

New evidence on prognostic features, prevention and treatment of congenital Cytomegalovirus infection.

PURPOSE OF REVIEW: Congenital Cytomegalovirus (CMV) infection remains a major cause of lifelong disability, with no systematic screening implemented in pregnancy or the postnatal period. In this review article, we outline the preventive strategies, antenatal prognostic features and experimental therapies as well as evidence of efficacy from recent trials. RECENT FINDINGS: A recent randomized, double blinded, placebo-controlled study investigated the efficacy of Valaciclovir in women contracting primary CMV in the periconception period or first trimester. They concluded that Valaciclovir at a dose of 8 g/day is effective in reducing the rate of foetal CMV infection following early maternal primary infection. Administration of CMV hyperimmune globulin (HIG) was investigated in a recent randomized double-masked controlled trial. This study concluded that CMV HIG was ineffective at reducing the risk of congenital CMV among women with primary CMV in early pregnancy. SUMMARY: Congenital CMV infection remains a significant cause of disability. There is currently no vaccine available, with the best preventive strategy being patient education on transmission as well as hygiene measures to reduce risk of exposure. Experimental therapies have been investigated in recent years and there is evidence supporting the use of Valaciclovir. Data for the efficacy of CMV HIG remains inconsistent and administration is currently limited to clinical trial settings.

Valacyclovir in primary maternal CMV infection for prevention of vertical transmission: A case-series.

BACKGROUND: No treatment is currently approved for cytomegalovirus infection in pregnancy. Valacyclovir has been studied in symptomatic cytomegalovirus infected fetuses and seems to reduce the risk of serious sequelae. OBJECTIVES: We used off-label valacyclovir on pregnant women with primary cytomegalovirus infection to reduce the risk of fetal infection. STUDY DESIGN: We treated 12 pregnant women with 8 g/day valacyclovir after diagnosis of cytomegalovirus infection until amniocentesis. We continued treatment until delivery in case of fetal infection. We periodically performed serology and virology tests on the women from referral until delivery and monitored them for adverse effects while on treatment. All women underwent late amniocentesis. We followed up infants for 5-28 months. RESULTS: At the time of amniocentesis, we observed a transmission rate of 17 %, and at birth we observed a transmission rate of 42 %. Two women with negative amniocentesis and infected newborns had viremia reactivation after valacyclovir discontinuation. We observed no symptomatic infections at birth and one isolated sensory-neural hearing loss at follow-up. CONCLUSIONS: This is the first series of antiviral treatment in women with a diagnosis of cytomegalovirus infection before amniocentesis. Valacyclovir may control cytomegalovirus infection while it is administered and reduce transmission at amniocentesis. Late transmission after treatment discontinuation is a risk. We advocate the need for a controlled trial of valacyclovir therapy starting from diagnosis of maternal infection until delivery, regardless of prenatal diagnosis of infection.

Multiple cranial nerve injury in Ramsay Hunt Syndrome: a case report.

Herpes zoster oticus (Ramsay Hunt Syndrome) is characterized by facial nerve paralysis, ear pain and auricular skin rash. It occurs as a result of reactivation oflatent varicella zoster virus infection in the geniculate ganglion of the facial nerve. Major clinical symptoms include 7th nerve paralysis or cranial nerve paralysis and vesicles along the nerve with cocomitant ear pain. Other cranial nerve involvement although uncommon, can be found in some cases. In this study, a 74-year-old female patient had ipsilateral 8th, 9th and 10th cranial nerves injury. Cranial nerve paralysis accompanied with injury has been repor ted in R amsay Hunt Syndrome.

Cytomegalovirus infection during pregnancy: state of the science.

Cytomegalovirus is the most common congenital infection, affecting 0.5-2% of all live births and the main nongenetic cause of congenital sensorineural hearing loss and neurological damage. Congenital cytomegalovirus can follow maternal primary infection or nonprimary infection. Sensorineurological morbidity is confined to the first trimester with up to 40-50% of infected neonates developing sequelae after first-trimester primary infection. Serological testing before 14 weeks is critical to identify primary infection within 3 months around conception but is not informative in women already immune before pregnancy. In Europe and the United States, primary infection in the first trimester are mainly seen in young parous women with a previous child younger than 3 years. Congenital cytomegalovirus should be evoked on prenatal ultrasound when the fetus is small for gestation and shows echogenic bowel, effusions, or any cerebral anomaly. Although the sensitivity of routine ultrasound in predicting neonatal symptoms is around 25%, serial targeted ultrasound and magnetic resonance imaging of known infected fetuses show greater than 95% sensitivity for brain anomalies. Fetal diagnosis is done by amniocentesis from 17 weeks. Prevention consists of both parents avoiding contact with body fluids from infected individuals, especially toddlers, from before conception until 14 weeks. Candidate vaccines failed to provide more than 75% protection for >2 years in preventing cytomegalovirus infection. Medical therapies such as cytomegalovirus hyperimmune globulins aim to reduce the risk of vertical transmission but 2 randomized controlled trials have not found any benefit. Valaciclovir given from the diagnosis of primary infection up to amniocentesis decreased vertical transmission rates from 29.8% to 11.1% in the treatment group in a randomized controlled trial of 90 pregnant women. In a phase II open-label trial, oral valaciclovir (8 g/d) given to pregnant women with a mildly symptomatic fetus was associated with a higher chance of delivering an asymptomatic neonate (82%), compared with an untreated historical cohort (43%). Valganciclovir given to symptomatic neonates is likely to improve hearing and neurological symptoms, the extent of which and the duration of treatment are still debated. In conclusion, congenital cytomegalovirus infection is a public health challenge. In view of recent knowledge on diagnosis and pre- and postnatal management, health care providers should reevaluate screening programs in early pregnancy and at birth.

Retransplantation after post transplant lymphoproliferative disorder: overcoming the obstacles!

Post transplant lymphoproliferative disorder (PTLD) is a rare complication after kidney transplantation. Graft dysfunction is often encountered during the course of the treatment of PTLD, at times leading to need for retransplantation. We describe here the case of a young boy who underwent retransplantation after treatment of early Epstein Barr virus (EBV) related post transplant lymphoproliferative disorder. Our case highlights the various factors needing deliberation before retransplantation including time from remission of PTLD, EBV serostatus and choice of induction and maintenance immunosuppression agents.