Comparative study on corneal epithelium healing: effects of crosslinked hyaluronic acid and amniotic membrane extract eye drops in rats.

Introduction: Corneal ulcers are common lesions in both human and veterinary medicine. However, only a few studies have evaluated the efficacy of cross-linked hyaluronic acid (X-HA) eye drops on corneal wound healing. To our knowledge, this is the first study to demonstrate and compare the efficacy of amniotic membrane extract eye drops (AMEED) and X-HA for corneal wound healing in rats. Material and methods: A total of 15 male Wistar rats (30 eyes) were used in this study. Then, 10 eyes were treated with X-HA, AMEED, or 0.9% saline. After general and topical anesthesia, a superficial corneal ulcer was created using a corneal trephine. The defect was further polished with a diamond burr. Three groups of 10 eyes each were treated with either one drop of 0.75% X-HA or AMEED or 0.9% saline (control), administered every 12 h for a duration of 72 h. The median epithelial defect area (MEDA), expressed as a percentage of the total corneal surface, was measured at 0, 12, 24, 36, 48, and 72 h. Re-epithelization time scores were also evaluated. The Kruskal-Wallis test was used to compare median times for re-epithelization and histopathologic scores between groups, while the Friedman test (for paired data) was employed to compare results from the serial analysis of MEDA and vascularization scores between groups. Results: MEDA was not significantly different between X-HA and AMEED. However, MEDA was significantly smaller in the X-HA group compared to the control group at 36 h (2.73 interquartile range (IQR) 5.52% x 9.95 IQR 9.10%, P=0.024) and 48 h (0.00 IQR 0.26% x 6.30 IQR 8.54%, P=0.030). The overall time for re-epithelization was significantly lower in the X-HA group (3.00 IQR 3.00) compared to the AMEED (6.5 IQR 3.00) and control (7.00 IQR 1.00) groups (P=0.035). Vascularization, hydropic degeneration, and epithelial-stromal separation were significantly less observed in samples in the X-HA-treated compared to samples in the AMEED- and saline-treated groups. Significantly more corneal epithelium cells were labeled for caspase3 in samples from the AMEED- and saline-treated groups compared to those from the X-HA-treated group. Discussion: Topical X-HA has been shown to accelerate corneal epithelial healing. AMEED did not decrease corneal re-epithelialization time. X-HA may also potentially be used as an adjunct therapy for treating corneal ulcers in clinical situations.

Acute Kidney Injury in the Context of COVID-19: An Analysis in Hospitalized Mexican Patients.

During the COVID-19 pandemic, a considerable proportion of patients developed a severe condition that included respiratory failure, shock, or multiple organ dysfunction. Acute Kidney Injury (AKI) has been recognized as a possible cause of severe COVID-19 development. Given this, this study investigates the occurrence and consequences of AKI in Mexican patients to contribute to better knowledge and management of this problem. Methods: Using a retrospective observational cohort methodology, we investigated 313 cases from a cohort of 1019 patients diagnosed with COVID-19 at the IMSS Zacatecas General Hospital of Zone No. 1 in 2020. The prevalence of AKI was determined using the AKIN criteria based on serum creatinine levels and a detailed review of demographic characteristics, medical history, comorbidities, and clinical development. Results: The data showed a 25.30% prevalence of AKI among patients infected with severe COVID-19. Remarkably, these patients with AKI exhibited an advanced age (>65 years), arterial hypertension, a higher number of white blood cells during admission and the hospital stay, and elevated levels of C-reactive protein, serum creatinine, and blood urea nitrogen (BUN). Clinically, patients with AKI had signs of prostration, pneumonia, and the requirement for ventilatory assistance when compared to those without AKI. Finally, those diagnosed with AKI and COVID-19 had a 74% death rate. Relative risk analyses indicated that age (>65 years), arterial hypertension, high creatinine levels, endotracheal intubation, and pneumonia are associated with the development of AKI. On the other hand, among the protective factors against AKI, high hemoglobin levels and the consumption of statins during COVID-19 were found. Conclusions: The findings of this study underscore the significance of promptly identifying and effectively managing AKI to potentially alleviate the negative consequences of this complication within the Mexican population during COVID-19.

Pharmacokinetics and pharmacodynamics of dextroketamine alone or combined with midazolam in Caiman crocodilus.

Pharmacokinetics studies of anesthetic agents are important for understanding of the pharmacology and metabolism of anesthetic agents in reptilians. This study was designed to examine the pharmacokinetic and pharmacodynamic properties of intravenous dextroketamine alone or combined with midazolam in Caiman crocodilus. Eight caimans were anesthetized with dextroketamine (10 mg/kg; group D) or dextroketamine and midazolam (10 and 0.5 mg/kg respectively; group DM) into the occipital venous sinus. The pharmacokinetic parameters were calculated by HPLC using a non-compartmental modeling. Serial blood samples were collected at baseline and within 15 and 30 min, and 11.5, 2, 4, 8, 12, 24 and 48 h of drug administration. Sedation status over time differed between groups. All animals in group D (8/8; 100%) showed signs of light sedation at t10. Half (4/8; 50%) of these caimans did not progress to deeper levels of sedation. In spite of light sedation at t10, animals in group DM were deeply sedated within 13.13 ± 7.04 min of anesthetic agent injection. The area under the plasma concentration-time curve (AUC0-48) and half-life of dextroketamine changed significantly after combination with midazolam. Even without significant changes in clearance, the almost two-fold increase in the half-life of dextroketamine suggests a slower rate of elimination.

A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection.

Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies.

p16 Immunohistochemical Expression in Nephrogenic Adenoma.

Nephrogenic adenoma (NA) is a rare metaplastic entity commonly associated with a prior urothelial injury. Most are seen in the urinary bladder and a minority involve the urethra. In this study, we evaluated the expression of p16 as a surrogate marker of this entity and correlated it with clinical pathological parameters. A total of 17 cases of NA were retrospectively studied to assess the immunohistochemical expression of p16 and its value for the diagnosis of this entity.

Laryngeal Sarcomatoid Carcinoma With Rhabdomyoblastic Differentiation: A Potential Pitfall for Misdiagnosis As Rhabdomyosarcoma.

Sarcomatoid carcinoma (SC) of the larynx is an uncommon subtype of squamous cell carcinoma which shows both squamous carcinoma and a sarcomatous component, including heterologous elements. The presence of rhabdomyosarcomatous elements in the larynx is extremely rare. Diagnosis of SC can be particularly challenging when the malignant epithelial component is not evident. We present a case of SC in a 72-year-old man with a superficial exophytic mass in the vocal cord initially misdiagnosed as rhabdomyosarcoma due to a predominant spindle cell component with rhabdomyoblastic features by morphology and immunohistochemistry. This case report aims to increase awareness that a rhabdomyoblastic heterologous component can be present in SC of the larynx and to consider this diagnosis in a mucosal exophytic malignant spindle cell neoplasm, even in the absence of epithelial differentiation.

Trigeminal Amyloidoma in a Patient With Cardiac Amyloidosis.

Trigeminal amyloidoma is a rare clinical phenomenon with scarce reports in the medical literature. This report presents a case of biopsy-proven trigeminal amyloidoma in a patient with cardiac amyloidosis. This case report sheds light on the differential diagnoses that may resemble trigeminal amyloidoma and strategies for workup and treatment.

Pericardiotomy by Transdiaphragmatic Thoracoscopy Singleport in Horses.

Thoracoscopy pericardiotomy consists of endoscopic access to the thoracic cavity to perform the opening of the pericardial sac, described in the equine species only through the intercostal access, and there are no studies addressing the singleport transdiaphragmatic access, so the objective was to develop the pericardiotomy technique by transdiaphragmatic thoracoscopy using a single port. The technique was performed using six cadavers of adult horses, positioned in dorsal decubitus, making it possible to initiate access with an incision in the region proximal to the xiphoid process, for the introduction of an 11 mm endotip trocar, which through the diaphragm reached the thoracic cavity. After accessing the thorax, a rigid endoscope with a working portal was entered, proceeding with the introduction of endoscopic scissors, used to open the pericardium. Pericardiotomy was initiated through the phrenic-pericardial ligament. After the procedure, the corpses were sent for necropsy for evaluation of inadvertent injuries and examination of the diaphragm and pericardium. The access allowed the visualization of the structures of the caudal portion of the thorax, in addition to the visualization and manipulation of the pericardium. The mean surgical time was 24.16 ± 7.03, allowing extensive pericardiotomy. It was concluded that transdiaphragmatic thoracoscopy is an adequate procedure for the visualization and access of the pericardium, as well as the structures present in the caudal region of both hemithoraxes. Therefore, the proposed technique, pericardiotomy by thoracoscopy using a singleport transdiaphragmatic approach, was promising, proving to be a viable alternative for pericardial procedures in the equine species.

Invasive Breast Carcinoma With Sebaceous Morphologic Pattern Showing Lymph Node Macrometastasis: A Case Report.

Invasive ductal carcinoma of no special type can present with various patterns. It is not possible to diagnose them through imaging alone. Microscopic examination is necessary to accurately identify and characterize them. The sebaceous pattern was historically considered a distinct subtype of breast carcinoma. However, the number of cases is relatively small and the prognosis has not been fully established. In this paper, we present a case of invasive ductal carcinoma with focal sebaceous features, which had a macrometastasis to the axillary lymph nodes showing the sebaceous morphology.

Short-term outcomes of heart transplant patients bridged with Impella 5.5 ventricular assist device.

AIMS: We sought to investigate the outcomes of heart transplant patients supported with Impella 5.5 temporary mechanical circulatory support. METHODS AND RESULTS: Patient demographics, perioperative data, hospital timeline, and haemodynamic parameters were followed during initial admission, Impella support, and post-transplant period. Vasoactive-inotropic score, primary graft failure, and complications were recorded. Between March 2020 and March 2021, 16 advanced heart failure patients underwent Impella 5.5 temporary left ventricular assist device support through axillary approach. Subsequently, all these patients had heart transplantation. All patients were either ambulatory or chair bound during their temporary mechanical circulatory support until heart transplantation. Patients were kept on Impella support median of 19 days (3-31) with the median lactate dehydrogenase level of 220 (149-430). All Impella devices were removed during heart transplantation. During Impella support, patients had improved renal function with median creatinine serum level of 1.55 mg/dL decreased to 1.25 (P = 0.007), pulmonary artery pulsatility index scores increased from 2.56 (0.86-10) to 4.2 (1.3-10) (P = 0.048), and right ventricular function improved (P = 0.003). Patients maintained improved renal function and favourable haemodynamics after their heart transplantation as well. All patients survived without any significant morbidity after their heart transplantation. CONCLUSIONS: Impella 5.5 temporary left ventricular assist device optimizes care of heart transplant recipients providing superior haemodynamic support, mobility, improved renal function, pulmonary haemodynamics, and right ventricular function. Utilizing Impella 5.5 as a direct bridging strategy to heart transplantation resulted in excellent outcomes.

Nephrogenic Adenoma Arising From a Female Urethral Diverticulum: A Case Report and Potential Diagnostic Pitfalls.

Nephrogenic adenoma is a benign lesion of the urothelial tract characterized by tubules surrounded by thick, hyalinized basement membranes. There is a great variety of architectural patterns within nephrogenic adenomas, including patterns that mimic malignancy, such as focal clear or hobnail cells, areas of significant nuclear atypia, mitosis, and isolated cystic changes. This represents a diagnostic pitfall, where a malignant lesion can be mistaken for a nephrogenic adenoma, leading to a delay in diagnosis and treatment that adversely affects the outcome. In this case report, we describe a nephrogenic adenoma arising in a female urethral diverticulum and discuss the differential diagnosis, which includes clear cell carcinomas, microcystic variant urothelial carcinomas, and Skene's gland cysts.

Preliminary characterization of a novel form of progressive retinal atrophy in the German Spitz dog associated with a frameshift mutation in GUCY2D.

OBJECTIVE: To describe the clinical, preliminary electroretinographic and optical coherence tomography features of a newly identified form of progressive retinal atrophy (PRA) in German Spitzes, and identify the causal gene mutation. ANIMALS: Thirty-three client-owned German Spitz dogs were included. PROCEDURES: All animals underwent a full ophthalmic examination, including vision testing. In addition, fundus photography, ERG, and OCT were performed. A DNA-marker-based association analysis was performed to screen potential candidate genes and the whole genomes of four animals were sequenced. RESULTS: Initial fundus changes were pale papilla and mild vascular attenuation. Oscillatory nystagmus was noted in 14 of 16 clinically affected puppies. Vision was impaired under both scotopic and photopic conditions. Rod-mediated ERGs were unrecordable in all affected dogs tested, reduced cone-mediated responses were present in one animal at 3 months of age and unrecordable in the other affected animals tested. Multiple small retinal bullae were observed in three clinically affected animals (two with confirmed genetic diagnosis). OCT showed that despite loss of function, retinal structure was initially well-preserved, although a slight retinal thinning developed in older animals with the ventral retina being more severely affected. Pedigree analysis supported an autosomal recessive inheritance. A mutation was identified in GUCY2D, which segregated with the disease (NM_001003207.1:c.1598_1599insT; p.(Ser534GlufsTer20)). Human subjects with GUCY2D mutations typically show an initial disconnect between loss of function and loss of structure, a feature recapitulated in the affected dogs in this study. CONCLUSION: We identified early-onset PRA in the German Spitz associated with a frameshift mutation in GUCY2D.

Prognostic Significance of p53 and p63 in Diffuse Large B-Cell Lymphoma: A Single-Institution Experience.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. We evaluated the immunohistochemical (IHC) expression of p63 and p53 in DLBCL and their significance on overall survival (OS) and progression-free survival (PFS). We conducted a retrospective cohort study of 177 patients with DLBCL who presented to Mount Sinai Medical Center of Florida (Miami Beach, Florida) between 2010 and 2020. IHC staining for p63 and p53 protein expression was performed. A significant correlation was found between p63 positivity and p53 expression, p53/p63 co-positivity, Ki-67 proliferation index, MYC expression, and MYC/BCL2 double expression. Regardless of the germinal center B-cell like (GCB) subgrouping, there was a trend among p53+ patients to have MYC/BCL2 double expression, positive MYC expression, and lower OS and PFS. A tendency of poor OS was seen in p53+ patients in the non-GCB, GCB, and double expressors subgroups and poor PFS in p53+ patients regardless of the subgrouping. In conclusion, our results suggest that p63 and p53 may represent potential additional prognostic biomarkers in DLBCL and may be included in the initial diagnostic work up of patients with DLBCL.

A review of transthyretin cardiac amyloidosis.

Transthyretin cardiac amyloidosis is a progressive disease known to cause heart failure, conduction anomalies, and arrythmias. Due to poor outcomes and mortality from severe cardiomyopathy, prevalence and incident rates are often underreported. As global longevity is increasing and rates of amyloidosis are also increasing, there is a need to improve diagnostic and therapeutic interventions. Previously, symptom management and transplantation were the mainstay of treatment for heart failure symptoms, but studies using RNAi and siRNA technologies have shifted the paradigm of therapeutic strategy in amyloid cardiomyopathy management. Additionally, early detection and clinical monitoring with numerous imaging and non-imaging techniques are being increasingly investigated. Here, we review the epidemiology, pathophysiology, diagnosis, and management of transthyretin amyloid cardiomyopathy.

Clinicopathological analysis of recurrence and progression of low-grade papillary urothelial carcinoma of the urinary bladder: Predicting the outcome.

BACKGROUND: Urothelial carcinoma of the urinary bladder is the most common malignancy of the urinary system. Patients with low grade papillary urothelial carcinoma (LGPUC) usually have a low risk for tumor recurrence and progression; yet a subset of patients develop recurrence or grade/stage progression to high-grade papillary urothelial carcinoma (HGPUC). The clinicopathological and molecular factors that contribute to this progression are yet to be determined. OBJECTIVES: In our study, we aimed to assess the incidence and clinicopathological factors associated with tumor recurrence/progression of LGPUC. METHODS: Using a pathological database of surgical specimens from patients who underwent bladder biopsies and/or transurethral resection of bladder tumors (TURBTs) between August 01, 2011, and July 31, 2021, at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 258 patients included, 157 (60.9 %) had "no recurrence", 85 (32.9 %) had ≥1 "recurrence of LGPUC", and 16 (6.2 %) had "grade progression to HGPUC". The mean follow-up time was 31.5 ± 32 months. Patients with "grade progression" and "recurrence of LGPUC" had larger mean tumor size on initial biopsy and multiple lesions on initial cystoscopy compared to those with "no recurrence." Interestingly, former smokers had 2.5- and 8.5-times higher risk of recurrence of LGPUC and grade progression, respectively. CONCLUSION: Since the majority of our patients did not develop recurrence, we question whether there is tendency to overclassify the papillomas as LGPUC based on the 2004 WHO/ISUP consensus grading classification.

Packing the donor heart: Is SherpaPak cold preservation technique safer compared to ice cold storage.

INTRODUCTION: The present study aimed to compare the clinical outcomes of heart transplant patients whose donor hearts were preserved with the SherpaPak controlled cold organ system versus the conventional ice storage technique. METHODS: All patients undergoing heart transplantation at our center between January 2019 and April 2021 were divided into two groups according to the technique used during donor heart preservation and transport. The first group consisted of 34 SherpaPak controlled temperature preservation patients, and the second group consisted of 47 patients where the conventional three bags and ice technique was utilized during organ transportation. The two groups were compared based on demographics, operative details, and postoperative outcomes. RESULTS: There were no significant differences between the groups regarding Vasoactive Inotropic Score (VIS), Primary Graft Dysfunction (PGD), and the need for a transient pacer. However, the VIS, PGD, and pacing trends were lower in the SherpaPak patients even though the total ischemic and cardiopulmonary bypass times were significantly longer. Furthermore, SherpaPak patients exhibited a shorter stay in the ICU with no severe PGD and mortality. CONCLUSION: The SherpaPak donor heart preservation provides safe outcomes in heart transplant patients. Further research is needed to utilize this method for longer durations of ischemic time and expand travel distances for organ transportation.

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.