Multimodal imaging in a case of presumed secondary vitreoretinal lymphoma presenting with inner retina and optic nerve head infiltration.

Purpose: To report the findings supported by multimodal imaging in a case of secondary vitreoretinal lymphoma presenting with inner retina and optic nerve head infiltration. Observations: A 64-year-old man with systemic diffuse large B-cell lymphoma presented with reduced visual acuity. Moderate anterior chamber and vitreous cell were present. Fundus exam showed bilateral disc edema and diffuse opaque macular infiltrates with a pseudo cherry-red spot in the left eye. Optical coherence tomography showed inner retinal infiltration and loss of normal architecture. Surgery for tissue biopsy was discussed and declined due to risk. Instead, multimodal imaging and anterior chamber fluid sampling were used as a surrogate for tissue biopsy and helped rule out infectious uveitis and retinal vascular disease. The patient was empirically treated with intravitreal methotrexate with rapid improvement in vision, exam, and quality of life. Conclusions and importance: Multimodal imaging can support a presumed diagnosis of secondary vitreoretinal lymphoma in order to proceed with intravitreal methotrexate treatment, which can result in rapid clinical and visual improvement.

A review of robotic-assisted laparoscopic partial nephrectomy in the management of renal duplication anomalies.

Open and purely laparoscopic partial nephrectomy or heminephrectomy has been the standard management for renal duplication anomalies for symptomatic children with non-functional renal moieties. While robotic-assisted laparoscopic partial nephrectomy (RALPN) has been established as a safe and feasible option for the management of renal duplex anomalies, there remains a paucity of data on this topic. The aim of this study is to comprehensively review all available outcomes data and update the use of emerging technologies in robotic surgery which continue to make RALPN a viable and advantageous option in the management of renal duplex anomalies.

Intermittent and Unilateral Chorioretinal Folds due to Combined Chiari 1 Malformation and Basilar Invagination.

We report the case of a 35-year-old female with combined Chiari 1 malformation and basilar invagination, who presented with intermittent conjunctival chemosis and unilateral chorioretinal folds that were temporally correlated. She denied any flashes, floaters, eye redness, or pain. She also denied nausea or vomiting. Clinical exam and optical coherence tomography imaging revealed conjunctival chemosis and chorioretinal folds in the left eye. Subsequent magnetic resonance imaging of the brain and the orbits were consistent with combined Chiari 1 malformation and basilar invagination. The unilateral and intermittent chorioretinal folds and conjunctival chemosis presentation of combined Chiari 1 malformation and basilar invagination is unusual. To the best of our knowledge, this is the first case to be reported with this unique clinical presentation. It is most important to be aware that unilateral and intermittent chorioretinal folds associated with conjunctival chemosis may be signs of intracranial disease.

Acute Kidney Injury in Dengue Fever: A One-year Hospital-based Prospective Cross-sectional Study.

BACKGROUND AND OBJECTIVES: Dengue fever is amongst the most cardinal arthropod-borne infection among humans. Around the world, an estimated 2.5 billion individuals are at peril of infection, of which approximately 975 million reside in urban areas of tropical and subtropical nations like Southeast Asia, the Pacific, and surprisingly Americas. Acute kidney injury (AKI) is so far not a well-studied dengue complication. The renal abnormalities, though not common, are AKI, proteinuria, glomerulonephritis, and hemolytic uraemic syndrome, which are considered complications of the disease. This study was designed to evaluate the prevalence of AKI in DF and find out the predictors of the development of AKI in patients with DI. METHODOLOGY: This one-year hospital-based cross-sectional study was performed in the Department of General Medicine, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala from March 2020 to April 2021. A total of 120 eligible patients with DI were enrolled. These patients were evaluated for AKI based on acute kidney injury network (AKIN) criteria. RESULTS: The majority of the patients were males 57.5% and the male to female ratio was 1.35:1. Most of the patients were aged between 31 and 50 years (40.8%) and the mean age was 42.23 ± 16.28 years. The majority of the patients (72.5%) had DF, 13.3% of the patients had dengue fever with warning signs and 14.2% of the patients had severe dengue. The prevalence of AKI was 27.5% in patients with dengue fever. Other than AKI, Acute respiratory distress syndrome (ARDS) (11.7%), Multiple Organ Dysfunction Syndrome (MODS) (3.3%), and sepsis (0.8%) were the complications noted. The majority of the patients (83.3%) improved and were discharged and mortality was noted in 16.7% of the patients. Also, significant differences were noted in patients with and without AKI.

Clinical Features and Treatment Outcome of a Concurrent Central Retinal Vein Occlusion and Cilioretinal Artery Occlusion.

We describe the clinical features and treatment outcome of a patient with combined central retinal vein occlusion and cilioretinal artery occlusion. A 52-year-old female presented to our clinic with decreased vision in the right eye for 4 days. Visual acuity and intraocular pressure were count fingers at 2&1/2M and 14 mm Hg in the right and 20/20 and 16 mm Hg in the left eye, respectively. Funduscopic exam and optical coherence tomography (OCT) of the right eye confirmed the diagnosis of concurrent cilioretinal artery occlusion and central retinal vein occlusion with segmental macular pallor in the territory of the cilioretinal artery, corresponding marked inner retina thickening on OCT and signs of vein occlusion. The patient received an intravitreal injection of bevacizumab and at 1-month follow-up, vision improved to 20/30 with corresponding anatomical improvement. It is very important to recognize combined central retinal vein occlusion and cilioretinal artery occlusion as they could be treated with intravitreal injections of anti-vascular endothelial growth factors with favorable treatment outcomes.

Melanoma metastasis to the bladder: A case report.

Metastasis of malignant melanoma to the bladder is rarely seen clinically with only 29 cases reported in English-language literature. However, autopsy series of melanoma patients have shown that metastasis to the bladder could be as high as 37%, implying that numerous cases remain undiagnosed. This report details a case of malignant melanoma metastasis to the bladder. Patient presented with severe anemia and history of gross hematuria. Computerized tomography (CT) revealed a 2.7 cm mass in the bladder. Cystoscopy confirmed presence of a mass. Patient underwent cystoscopy and transurethral resection of the tumor, revealed to be melanoma on pathology.

Inverted urothelial papilloma: A case report.

Inverted urothelial papilloma (IUP) is an unusual tumor that typically presents as a non-invasive, endophytic urothelial neoplasm. Though fairly well described in the bladder, IUP of the upper urinary tract is fairly rare, with only 68 cases documented in English language literature. Our patient presented with an IUP of the distal left ureter and was treated with a distal ureterectomy and reimplant of the ureter with a psoas hitch.

Association between nuclear grade of renal cell carcinoma and the aorta-lesion-attenuation-difference.

INTRODUCTION AND BACKGROUND: Several features noted on renal mass biopsy (RMB) can influence treatment selection including tumor histology and nuclear grade. However, there is poor concordance between renal cell carcinoma (RCC) nuclear grade on RMB compared to nephrectomy specimens. Here, we evaluate the association of nuclear grade with aorta-lesion-attenuation-difference (ALAD) values determined on preoperative CT scan. METHODS AND MATERIALS: A retrospective review of preoperative CT scans and surgical pathology was performed on patients undergoing nephrectomy for solid renal masses. ALAD was calculated by measuring the difference in Hounsfield units (HU) between the aorta and the lesion of interest on the same image slice on preoperative CT scan. The discriminative ability of ALAD to differentiate low-grade (nuclear grade 1 and 2) and high-grade (nuclear grade 3 and 4) tumors was evaluated by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) using ROC analysis. Sub-group analysis by histologic sub-type was also performed. RESULTS: A total of 368 preoperative CT scans in patients with RCC on nephrectomy specimen were reviewed. Median patient age was 61 years (IQR 52-68). The majority of patients were male, 66% (243/368). Tumor histology was chromophobe RCC in 7.6%, papillary RCC in 15.5%, and clear cell RCC in 76.9%. The majority, 69.3% (253/365) of tumors, were stage T1a. Nuclear grade was grade 1 in 5.46% (19/348), grade 2 in 64.7% (225/348), grade 3 in 26.2% (91/348), and grade 4 in 3.2% (11/348). Nephrographic ALAD values for grade 1, 2, 3, and 4 were 73.7, 46.5, 36.4, and 43.1, respectively (p = 0.0043). Nephrographic ALAD was able to differentiate low-grade from high-grade RCC with a sensitivity of 32%, specificity of 89%, PPV of 86%, and NPV of 36%. ROC analysis demonstrated the predictive utility of nephrographic ALAD to predict high- versus low-grade RCC with an AUC of 0.60 (95% CI 0.51-0.69). CONCLUSION: ALAD was significantly associated with nuclear grade in our nephrectomy series. Strong specificity and PPV for the nephrographic phrase demonstrate a potential role for ALAD in the pre-operative setting that may augment RMB findings in assessing nuclear grade of RCC. Although this association was statistically significant, the clinical utility is limited at this time given the results of the statistical analysis (relatively poor ROC analysis). Sub-group analysis by histologic subtype yielded very similar diagnostic performance and limitations of ALAD. Further studies are necessary to evaluate this relationship further.

Sequential endogenous endophthalmitis, fungal keratitis, bacteremia and vertebral osteomyelitis in a person who injects drugs.

PURPOSE: To describe multiple ocular (and non-ocular) manifestations of disease that can present in a person who injects drugs (PWID). We report a case of a patient consecutively presenting across multiple visits to an ambulatory eye care clinic as the initial point of contact for endogenous endophthalmitis, fungal keratitis, bacteremia, and psoas abscess with vertebral osteomyelitis within a matter of weeks. OBSERVATIONS: A 51-year-old male with past medical history of alcohol use disorder and injection drug use was initially seen in an eye clinic three days after suffering vision loss in the left eye associated with floaters, photophobia, and eye pain. After initial workup and treatment for panuveitis, endogenous endophthalmitis was suspected. A pars plana vitrectomy was performed, and intravitreal medications were given. A pathogen was never isolated from vitreous samples. Two weeks later, the patient presented with complaints of pain, blurry vision, and foreign body sensation in his opposite (right) eye. Examination revealed a corneal ulcer later identified as a Paecliomyces fungal infection. Two weeks after this, he developed fever, chills, and right-sided flank pain radiating to his testicles. Following evaluation by the emergency department and subsequent hospitalization after bacteremia was noted, he was found to have a right-sided psoas abscess with lumbar vertebral osteomyelitis. Fluid was drained, cultured, and grew methicillin-sensitive Staphylococcus aureus (MSSA). At his last visit, his best-corrected visual acuity was 20/20 OS and 20/30 OD despite central corneal scarring. It was only after hospitalization that he affirmed recent injection drug use, despite being queried about it through the course of his infections. CONCLUSIONS AND IMPORTANCE: Injection drug use is an increasingly common concern for all healthcare providers as the opioid crisis in the United States remains widespread. This case highlights multiple potential infectious processes which may impact persons who inject drugs when seen by eye care providers. It also describes difficulties in caring for people who inject drugs who may not provide critical and timely information relating to their injection drug use and/or may delay care even when faced with potentially vision- and/or life-threatening conditions.

Validation of aorta-lesion-attenuation difference on preoperative contrast-enhanced computed tomography scan to differentiate between malignant and benign oncocytic renal tumors.

OBJECTIVES: We previously noted that the aorta-lesion-attenuation difference (ALAD) determined on CT scan discriminated well between chromophobe RCC and oncocytoma. The current evaluation seeks to validate these initial findings in a second cohort of nephrectomy patients. METHODS: A retrospective review of preoperative CT scans and surgical pathology was performed on patients undergoing nephrectomy for small, solid renal masses. ALAD was calculated by measuring the difference in Hounsfield units (HU) between the aorta and the lesion of interest on the same image slice on preoperative CT scan. The discriminative ability of ALAD to differentiate malignant pathology from oncocytoma was evaluated by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) using ROC analysis. RESULTS: Twenty-one preoperative CT scans and corresponding pathology reports were reviewed and included in the validation cohort. ALAD values were calculated during the excretory and nephrographic phases. Compared to the training cohort, patients in the validation cohort were significantly older (62 versus 59 years old), had larger tumors (3.7 versus 2.7 cm), and higher stage disease (59% versus 79% T1a disease). Nephrographic ALAD was able to differentiate malignant pathology from oncocytoma in the training and validation cohorts with a sensitivity of 84% versus 73%, specificity of 86% and 67%, PPV of 98% versus 91%, and NPV of 33% versus 35%. The AUC for malignant pathology versus oncocytoma in the validation cohort was 0.72 (95% CI 0.63-0.82). Nephrographic ALAD was able to differentiate chromophobe RCC from oncocytoma in the training and validation cohorts with a sensitivity of 100% versus 67%, specificity of 86% versus 67%, PPV of 75% versus 43%, and NPV of 100% versus 84%. The AUC for chromophobe RCC versus oncocytoma in the validation cohort was 0.72 (95% CI 0.48-0.96). CONCLUSIONS: The ability of ALAD to discriminate between chromophobe RCC and oncocytoma was diminished in the validation cohort compared to the training cohort, but remained significant. The current findings support further investigation in the role of ALAD in the management of patients with indeterminate diagnoses of oncocytic neoplasm.

A narrative review of the history and evidence-base for the timing of orchidopexy for cryptorchidism.

INTRODUCTION: Consensus recommendations for surgical management of cryptorchidism recommend orchidopexy between 6 and 18 months of age. The COVID-19 pandemic has impacted elective surgical scheduling. OBJECTIVE: In response to the COVID-19 pandemic, we sought to review the available data regarding the natural history, surgical management, and infertility- and cancer-related risks associated with cryptorchid testes. The purpose of this review is to provide parents, referring providers, and surgeons with information to inform their decisions to proceed with or delay orchidopexy. METHODS: A retrospective review and analysis of all available articles relevant to the natural history, surgical management, and infertility- and cancer-related risks of cryptorchidism present on PubMed, SCOPUS, and Cochrane Library was conducted. RESULTS: The quality of historic literature pertaining to the effect of cryptorchidism on fertility and malignancy differ, with poorer data available on fertility. Cryptorchid testes may show histologic differences as early as birth, and some of these changes may have prognostic value in future fertility. Formerly unilateral cryptorchid men have slightly but not significantly reduced paternity rates compared to the general population. Cryptorchid testes have an increased risk of germ cell carcinogenesis, and robust data suggest the risk for malignancy in cryptorchid testes increases substantially after puberty. CONCLUSION: The current body of evidence regarding the risks for future infertility and testicular cancer support the consensus recommendations for surgical correction of cryptorchidism between 6 and 18 months of age. During the uncertain time of the COVID-19 pandemic, decision for orchidopexy is a shared-decision between physician and parent. For an infant or young boy with a unilateral undescended testes, delaying orchidopexy several months until a time of decreased exposure risk is unlikely to result in substantial or sustained fertility or malignant risks.

Endogenous endophthalmitis and other ocular manifestations of injection drug use.

PURPOSE OF REVIEW: The United States has experienced a dramatic rise in opioid and injection drug use over the past 2 decades. A public health emergency was declared in 2017 and subsequently, there have been several new reports on the rise of endogenous endophthalmitis specifically associated with injection drug use. The purpose of this review is to provide a current perspective of the ocular harms posed by injection drug use. RECENT FINDINGS: The opioid epidemic has prompted several new studies from New England, one of the US regions most heavily affected, that examine the trends and characteristics of injection drug use-associated endogenous endophthalmitis. Patients may delay seeking care and may be infected with a variety of rare and atypical microbes, and as a result clinical appearance may vary widely. Injection drug use also leads to embolic phenomena such as talc retinopathy and septic emboli from endocarditis. HIV is highly associated with injection drug use and although HAART has drastically reduced the morbidity and mortality of HIV-associated infections, a variety of ocular disease may accompany an immunocompromised patient. SUMMARY: Healthcare providers must remain vigilant in the recognition of injection drug use patients with vision loss and ocular inflammation to ensure prompt medical and/or surgical treatment.

Early detection of subclinical visual damage after blast-mediated TBI enables prevention of chronic visual deficit by treatment with P7C3-S243.

PURPOSE: Traumatic brain injury (TBI) frequently leads to chronic visual dysfunction. The purpose of this study was to investigate the effect of TBI on retinal ganglion cells (RGCs), and to test whether treatment with the novel neuroprotective compound P7C3-S243 could prevent in vivo functional deficits in the visual system. METHODS: Blast-mediated TBI was modeled using an enclosed over-pressure blast chamber. The RGC physiology was evaluated using a multielectrode array and pattern electroretinogram (PERG). Histological analysis of RGC dendritic field and cell number were evaluated at the end of the study. Visual outcome measures also were evaluated based on treatment of mice with P7C3-S243 or vehicle control. RESULTS: We show that deficits in neutral position PERG after blast-mediated TBI occur in a temporally bimodal fashion, with temporary recovery 4 weeks after injury followed by chronically persistent dysfunction 12 weeks later. This later time point is associated with development of dendritic abnormalities and irreversible death of RGCs. We also demonstrate that ongoing pathologic processes during the temporary recovery latent period (including abnormalities of RGC physiology) lead to future dysfunction of the visual system. We report that modification of PERG to provocative postural tilt testing elicits changes in PERG measurements that correlate with a key in vitro measures of damage: the spontaneous and light-evoked activity of RGCs. Treatment with P7C3-S243 immediately after injury and throughout the temporary recovery latent period protects mice from developing chronic visual system dysfunction. CONCLUSIONS: Provocative PERG testing serves as a noninvasive test in the living organism to identify early damage to the visual system, which may reflect corresponding damage in the brain that is not otherwise detectable by noninvasive means. This provides the basis for developing an earlier diagnostic test to identify patients at risk for developing chronic CNS and visual system damage after TBI at an earlier stage when treatments may be more effective in preventing these sequelae. In addition, treatment with the neuroprotective agent P7C3-S243 after TBI protects from visual system dysfunction after TBI.

Novel early response genes in osteoblasts exposed to dynamic fluid flow.

Cyclic mechanical loads applied to the skeleton from habitual physical activity result in increased bone formation. These loads lead to dynamic pressure gradients and oscillatory flow of bone interstitial fluid, which, in turn, exposes cells resident in the bony matrix to oscillatory fluid shear stress. Dynamic fluid flow has previously been shown to be a potent anabolic stimulus for cultured osteoblasts. In this study, we used cDNA microarrays to examine early phase, broad-spectrum gene expression in MC3T3-E1 osteoblasts in response to physical stimulation. RNA was harvested at 30 min and 1 h post-stimulation. RNA was used for microarray hybridization as well as subsequent reverse transcription polymerase chain reaction (RT-PCR) validation of expression levels for selected genes. Microarray results were analysed by both functional and expression profile clustering. We identified a small number of genes at both the 30 min and 1 h timepoints that were either upregulated or downregulated with flow compared to no-flow control by twofold or more. From the group of genes upregulated at 30 min, we selected nine for RT-PCR confirmation. All were found to be upregulated by at least twofold. We identify a novel set of early response genes potentially involved in mediating the anabolic response of MC3T3 osteoblasts to flow, and provide functional groupings of these genes that may shed light on the relevant mechanosensory pathways involved.

The role of actin cytoskeleton in oscillatory fluid flow-induced signaling in MC3T3-E1 osteoblasts.

Fluid flow due to loading in bone is a potent mechanical signal that may play an important role in bone adaptation to its mechanical environment. Previous in vitro studies of osteoblastic cells revealed that the upregulation of cyclooxygenase-2 (COX-2) and c-fos induced by steady fluid flow depends on a change in actin polymerization dynamics and the formation of actin stress fibers. Exposing cells to dynamic oscillatory fluid flow, the temporal flow pattern that results from normal physical activity, is also known to result in increased COX-2 expression and PGE(2) release. The purpose of this study was to determine whether dynamic fluid flow results in changes in actin dynamics similar to steady flow and to determine whether alterations in actin dynamics are required for PGE(2) release. We found that exposure to oscillatory fluid flow did not result in the development of F-actin stress fibers in MC3T3-E1 osteoblastic cells and that inhibition of actin polymerization with cytochalasin D did not inhibit intracellular calcium mobilization or PGE(2) release. In fact, PGE(2) release was increased threefold in the polymerization inhibited cells and this PGE(2) release was dependent on calcium release from the endoplasmic reticulum. This was in contrast to the PGE(2) release that occurs in normal cells, which is independent of calcium flux from endoplasmic reticulum stores. We suggest that this increased PGE(2) release involves a different molecular mechanism perhaps involving increased deformation due to the compromised cytoskeleton.

Effects of short-term recovery periods on fluid-induced signaling in osteoblastic cells.

It is well known that cyclic mechanical loading can produce an anabolic response in bone. In vivo studies have shown that the insertion of short-term recovery periods (10-15 s) into mechanical loading profiles led to an increased osteogenic response compared to continuous cyclic loading of bone. Although this is suggestive of temporal processing at the bone cell level, there is little evidence to support such a hypothesis. Therefore, the current study investigated the cellular mechanism of bone's response to rest inserted vs. continuous mechanical loading. Cell responses to rest inserted mechanical loading were quantified by applying oscillatory fluid flow (OFF) to osteoblastic cells and quantifying real-time intracellular calcium [Ca2+]i, prostaglandin E2 (PGE2) release, and osteopontin (OPN) mRNA levels. Cells were exposed to OFF (1 Hz) at shear stresses of 1 and 2 Pa with rest periods of 5, 10, and 15s inserted every 10 loading cycles. The insertion of 10 and 15s rest periods into the flow profile resulted in multiple [Ca2+]i responses by individual cells, increased [Ca2+]i response magnitudes, and increased overall percent of cells responding compared to continuously loaded control groups. We determined the source of the multiple calcium responses to be from intracellular stores. In addition, rest inserted OFF led to similar levels of PGE2 release and increased levels of relative OPN mRNA compared to cells exposed to continuous OFF. Our study suggests that the cellular mechanism of bone adaptation to rest inserted mechanical loading may involve modulation of intracellular levels of calcium (frequency, magnitude, percent of cells responding).

Oscillatory fluid flow affects human marrow stromal cell proliferation and differentiation.

Mechanical loading is an important regulator of bone formation and bone loss. Decreased osteoblast number and function are important cellular mechanisms by which mechanical disuse leads to decreased bone formation. Decreased osteoblast number may be a result of decreased osteoprogenitor proliferation, differentiation, or both. However, the effects of cellular level physical signals on osteoprogenitors are not well understood. In this study, we examined the effects of loading induced oscillatory fluid flow (OFF), a potent regulator of osteoblastic cell function, on marrow stromal cells (MSCs). MSCs subjected to OFF exhibited increased intracellular Ca2+ mobilization. In addition, MSCs exhibited increased proliferation and increased mRNA levels for osteopontin and osteocalcin genes. Collagen I and core binding factor 1 mRNA levels did not change. MSCs subjected to OFF also exhibited decreased alkaline phosphatase activity. These results suggest that MSCs are mechanosensitive and that Ca2+ may play a role in the signaling pathway.