Primary Carcinoid Tumor of the Ovary: A Case Report With Radiologic and Pathologic Correlation.

Ovarian carcinoid tumors are very rare entities that often mimic other ovarian neoplasms. A case of primary ovarian carcinoid in a 44-year-old woman is presented with emphasis on the magnetic resonance imaging (MRI) features of the tumor and pathologic correlation. Ovarian carcinoid tumors can be variable in their MRI appearance, presumably due to different tumor subtypes and tumor components, thus requiring pathologic diagnosis. It is imperative to accurately diagnose primary ovarian carcinoid tumors, as their prognosis is usually more favorable compared to other malignant ovarian neoplasms.

Intrathoracic plates versus extrathoracic plates: a comparison of postoperative pain in surgical stabilization of rib fracture technique.

Background: Surgical stabilization of rib fractures (SSRF) has been shown to improve outcomes, yet there is an absence of studies comparing SSRF techniques. An intrathoracic system that minimizes incision length has recently been developed and adopted by multiple institutions. We hypothesized that SSRF with an intrathoracic system plus intercostal nerve cryoneurolysis (IC) leads to improved pain control compared with an extrathoracic system plus IC. Methods: A single-center, retrospective chart review was performed comparing intrathoracic SSRF versus extrathoracic SSRF, and included patients undergoing SSRF from 2015 to 2021 at a level 1 trauma center. Patients who did not undergo intercostal nerve cryoablation were excluded. The primary outcome was opioid consumption based on morphine milligram equivalent (MME) consumption. We collected Rib score, Blunt Pulmonary Contusion 18 Score, number of rib fractures, number of ribs plated, and Injury Severity Score (ISS) to compare baseline characteristics of each group. Results: A total of 112 patients were evaluated for study inclusion. Thirty-one patients were excluded due to missing outcomes data and/or lack of cryoablation. There was no difference in ISS or Rib Score between the intrathoracic (n=33) and extrathoracic (n=48) groups. At 7-day follow-up, the median MME requirement was significantly lower in the intrathoracic group (21.25) versus the extrathoracic group (46.20) (p=0.02). Conclusion: Intrathoracic SSRF was associated with a lower postoperative MME consumption compared with extrathoracic SSRF. These data support the use of intrathoracic SSRF to improve pain control compared to extrathoracic SSRF. Level of evidence: III.

Chemotherapy-associated liver morphological changes in hepatic metastases (CALMCHeM).

PURPOSE: To review imaging findings in chemotherapy-associated liver morphological changes in hepatic metastases (CALMCHeM) on computed tomography (CT)/magnetic resonance imaging (MRI) and its association with tumor burden. METHODS: We performed a retrospective chart review to identify patients with hepatic metastases who received chemotherapy and subsequent follow-up imaging where CT or MRI showed morphological changes in the liver. The morphological changes searched for were nodularity, capsular retraction, hypodense fibrotic bands, lobulated outline, atrophy or hypertrophy of segments or lobes, widened fissures, and one or more features of portal hypertension (splenomegaly/venous collaterals/ascites). The inclusion criteria were as follows: a) no known chronic liver disease; b) availability of CT or MRI images before chemotherapy that showed no morphological signs of chronic liver disease; c) at least one follow-up CT or MRI image demonstrating CALMCHeM after chemotherapy. Two radiologists in consensus graded the initial hepatic metastases tumor burden according to number (≤10 and >10), lobe distribution (single or both lobes), and liver parenchyma volume affected (<50%, or ≥50%). Imaging features after treatment were graded according to a pre-defined qualitative assessment scale of "normal," "mild," "moderate," or "severe." Descriptive statistics were performed with binary groups based on the number, lobar distribution, type, and volume of the liver affected. Chi-square and t-tests were used for comparative statistics. The Cox proportional hazard model was used to determine the association between severe CALMCHeM changes and age, sex, tumor burden, and primary carcinoma type. RESULTS: A total of 219 patients met the inclusion criteria. The most common primaries were from breast (58.4%), colorectal (14.2%), and neuroendocrine (11.0%) carcinomas. Hepatic metastases were discrete in 54.8% of cases, confluent in 38.8%, and diffuse in 6.4%. The number of metastases was >10 in 64.4% of patients. The volume of liver involved was <50% in 79.8% and ≥50% in 20.2% of cases. The severity of CALMCHeM at the first imaging follow-up was associated with a larger number of metastases (P = 0.002) and volume of the liver affected (P = 0.015). The severity of CALMCHeM had progressed to moderate to severe changes in 85.9% of patients, and 72.5% of patients had one or more features of portal hypertension at the last follow-up. The most common features at the final follow-up were nodularity (95.0%), capsular retraction (93.4%), atrophy (66.2%), and ascites (65.7%). The Cox proportional hazard model showed metastases affected ≥50% of the liver (P = 0.033), and the female gender (P = 0.004) was independently associated with severe CALMCHeM. CONCLUSION: CALMCHeM can be observed with a wide variety of malignancies, is progressive in severity, and the severity correlates with the initial metastatic liver disease burden.

Identifying and Managing Patients with Elevated Breast Cancer Risk Presenting for Screening Mammography.

BACKGROUND: Identifying the prevalence and management of patients at high-risk for breast cancer can improve resource utilization and provide individualized screening strategies. OBJECTIVE: The purpose of this study was to identify the prevalence of high-risk patients in our institution who presented for screening mammography and to understand how they utilized downstream resources offered to them. MATERIALS AND METHODS: This single institution retrospective study utilized the Tyrer-Cuzick risk assessment model to provide lifetime risk of breast cancer of patients presenting for screening mammography over a one-year period. Their subsequent management and resource utilization were collated. RESULTS: High-risk patients comprised 7.7% (701/9061) of our screening population. Of those high-risk women offered a Breast Center (BC) consultation, 75.2% (276/367) participated in the consultation, with 51.1% (141/276) of those patients completing MRI for supplemental screening. Risk reducing medication was adopted by 7.6% (6/79) of those offered. Of patients offered a genetics consultation, 66.3% (53/80) participated in the consultation, and 50.0% (40/80) completed genetic testing. CONCLUSIONS: Identifying and understanding high-risk patient cohorts, whether locally or in a population-based context, is important for individualized patient care and practice efficiency.

Prophylactic Intravenous Access: Is It Necessary for Renal Transplant Biopsies?

INTRODUCTION: Percutaneous renal transplant biopsies have long been a safe and effective procedure with bleeding being the most common significant complication. Only a few studies, however, have addressed the need for intravenous access prior to the procedure. OBJECTIVES: We postulate that the number of patients requiring intravenous resuscitation after a routine renal transplant biopsy is sufficiently low enough to prove that eliminating pre-procedural peripheral IV placement will have no negative impact on patient safety and could improve departmental efficiency. METHODS: This is a retrospective analysis of complications that occurred in patients who underwent routine percutaneous renal transplant biopsies at an academic center. Patients were divided into two groups: the IV cohort that had peripheral IV access placed before the procedure (n=1318) and the no-IV cohort that did not (n=492). RESULTS: This is a retrospective analysis of complications that occurred in patients who underwent routine percutaneous renal transplant biopsies at an academic center. Patients were divided into two groups: the IV cohort that had peripheral IV access placed before the procedure (n=1318) and the no-IV cohort that did not (n=492). CONCLUSIONS: Placement of prophylactic peripheral IV access in patients undergoing routine renal transplant biopsies does not significantly impact the rate of biopsy complications.

Thyroid Ultrasound: Diffuse and Nodular Disease.

Thyroid ultrasound with gray-scale and color Doppler is the most helpful imaging modality to differentiate normal thyroid parenchyma from diffuse or nodular thyroid disease by evaluating glandular size, echogenicity, echotexture, margins, and vascularity. The various causes of diffuse thyroid disease often have overlapping sonographic imaging features. Thyroid nodules may be hyperplastic or neoplastic, with most due to benign hyperplastic changes in architecture and benign follicular adenomas; only a small percentage are malignant. A systematic approach to nodule morphology that includes evaluation of composition, echogenicity, margin, shape, and any echogenic foci can guide decision to biopsy or follow nodules.

Development of complex renal cysts: A complication associated with Crizotinib therapy.

Crizotinib is a tyrosine kinase inhibitor that has been found to be effective in the treatment of anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer. This targeted cancer therapy agent has been shown to have superior efficacy over standard chemotherapy in this small subset of lung cancer patients. An adverse effect of this drug therapy is the development of complex renal cysts. Here, we present a case of a 68-year-old patient with non-small cell lung cancer on Crizotinib therapy who developed complex bilateral renal cysts. It is important to recognize this drug-related complication in order to avoid mistaking it for disease progression, primary renal malignancy, or renal infection.

Phosphodiesterases PDE2A and PDE10A both change mRNA expression in the human brain with age, but only PDE2A changes in a region-specific manner with psychiatric disease.

Many studies implicate altered cyclic nucleotide signaling in the pathophysiology of major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SCZ). As such, we explored how phosphodiesterases 2A (PDE2A) and 10A (PDE10A)-enzymes that break down cyclic nucleotides-may be altered in brains of these patients. Using autoradiographic in situ hybridization on postmortem brain tissue from the Stanley Foundation Neuropathology Consortium, we measured expression of PDE2 and PDE10 mRNA in multiple brain regions implicated in psychiatric pathophysiology, including cingulate cortex, orbital frontal cortex (OFC), superior temporal gyrus, hippocampus, parahippocampal cortex, amygdala, and the striatum. We also assessed how PDE2A and PDE10A expression changes in these brain regions across development using the Allen Institute for Brain Science Brainspan database. Compared to controls, patients with SCZ, MDD and BPD all showed reduced PDE2A mRNA in the amygdala. In contrast, PDE2A expression changes in frontal cortical regions were only significant in patients with SCZ, while those in caudal entorhinal cortex, hippocampus, and the striatum were most pronounced in patients with BPD. PDE10A expression was only detected in striatum and did not differ by disease group; however, all groups showed significantly less PDE10A mRNA expression in ventral versus dorsal striatum. Across development, PDE2A mRNA increased in these brain regions; whereas, PDE10A mRNA expression decreased in all regions except striatum. Thus, PDE2A mRNA expression changes in both a disorder- and brain region-specific manner, potentially implicating PDE2A as a novel diagnostic and/or patient-selection biomarker or therapeutic target.

Identification of new PDE9A isoforms and how their expression and subcellular compartmentalization in the brain change across the life span.

3',5'-Cyclic nucleotide phosphodiesterases (PDEs) degrade 3',5' cyclic adenonosine monophosphate (cAMP) and 3',5' cyclic guanosine monophosphate (cGMP), with PDE9A having the highest affinity for cGMP. We show PDE9A6 and 3 novel PDE9 isoforms (PDE9X-100, PDE9X-120, and PDE9X-175) are reliably detected in the brain and lung of mice, whereas PDE9A2 and other isoforms are found elsewhere. PDE9A localizes to the membrane in all organs except the bladder, where it is cytosolic. Brain additionally shows PDE9 in the nuclear fraction. PDE9A mRNA expression/localization dramatically changes across neurodevelopment in a manner that is strikingly consistent between mice and humans (i.e., decreased expression in the hippocampus and cortex and inverted-U in the cerebellum). Study of the 4 PDE9 isoforms in the mouse brain from postnatal day 7 through 24 months similarly identifies dramatic effects of age on expression and subcellular compartmentalization that are isoform specific and brain region specific. Finally, PDE9A mRNA is elevated in the aged human hippocampus with dementia when there is a history of traumatic brain injury. Thus, brain PDE9 is localized to preferentially regulate nuclear- and membrane-proximal pools of cGMP, and its function likely changes across the life span.

Treatment of a glioblastoma multiforme dural metastasis with stereotactic radiosurgery: A case report and select review of the literature.

Glioblastoma multiforme (GBM) is a primary brain neoplasm accounting for approximately 75% of all high grade gliomas. It is diffusely infiltrative and exhibits rapid proliferation with a poor overall prognosis. Maximum surgical resection and postoperative radiotherapy, accompanied by concurrent and adjuvant temozolomide chemotherapy, remain the standard of care without major therapeutic advances over the past 10 years. Herein, we present the case of a 64-year-old Caucasian male with a GBM who subsequently developed a left frontal dural metastasis, subsequently treated with stereotactic radiosurgery (20 Gy in 1 fraction). With six month follow-up, the patient showed near complete resolution of his dural metastases and no overall change in neurological symptoms or side effects following radiosurgery. Due to the paucity of clinical literature regarding dural metastases from GBM, its optimal treatment remains unknown. While the role of SRS has yet to be defined in this setting, here we provide evidence suggesting its overall efficacy in the treatment of select dural GBM metastases.

Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes-MELAS Syndrome.

BACKGROUND: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder that results in waxing and waning nervous system and muscle dysfunction. MELAS syndrome may overlap with other neurologic disorders but shows distinctive imaging features. CASE REPORT: We present the case of a 28-year-old female with atypical stroke-like symptoms, a strong family history of stroke-like symptoms, and a relapsing-remitting course for several years. We discuss the imaging features distinctive to the case, the mechanism of the disease, typical presentation, imaging diagnosis, and disease management. CONCLUSION: This case is a classic example of the relapse-remitting MELAS syndrome progression with episodic clinical flares and fluctuating patterns of stroke-like lesions on imaging. MELAS is an important diagnostic consideration when neuroimaging reveals a pattern of disappearing and relapsing cortical brain lesions that may occur in different areas of the brain and are not necessarily limited to discrete vascular territories. Future studies should investigate disease mechanisms at the cellular level and the value of advanced magnetic resonance imaging techniques for a targeted approach to therapy.

A Large Cohort Study of 18F Fluoro-Deoxy-Glucose Uptake in Normal Spinal Cord: Quantitative Assessment of the Contamination From Adjacent Vertebral Marrow Uptake and Validity of Normalizing the Cord Uptake Against the Lumbar Thecal Sac.

PURPOSE: This study aimed (1) to assess the influence of age, sex, blood glucose, and body mass index on the F fluoro-deoxy-glucose (F-FDG) uptake in normal spinal cord; (2) to quantitatively evaluate contamination of the spinal cord SUVmax by the adjacent vertebral marrow activity; and (3) to investigate the validity of normalizing spinal cord SUVmax against lumbar thecal sac SUVmax. METHODS: Two hundred positron emission tomography-computed tomography examinations of subjects with normal spinal cord were retrospectively reviewed. SUVmax of spinal cord and vertebral body was obtained at C2, C5, T6, T12, and L3 levels. Pearson correlation coefficients (r) were obtained at each level between spinal cord SUVmax and vertebral marrow SUVmax, age, body mass index, and blood glucose. Cord to background ratio (CTB) was calculated as the ratio between SUVmax of spinal cord and SUVmax of L3 thecal sac. The coefficient of variation (CV) of spinal cord SUVmax was compared with the CV of CTB. RESULTS: Spinal cord SUVmax was highest at C2 (mean, 1.76) and lowest at T6 (mean, 1.37) with SD of 0.32 to 0.36 SUV. Sex (P > 0.45), age (r: -0.25 to -0.06), body mass index (r: 0.19 to 0.27), and blood glucose (r: -0.17 to 0.22) had no impact on the spinal cord SUVmax. A moderate to strong positive correlation (r: 0.66-0.80) was found between spinal cord SUVmax and the corresponding vertebral marrow SUVmax. The CV of CTB was greater (0.28-0.32) than the CV of spinal cord SUVmax (0.19-0.25) across all levels. CONCLUSIONS: Of the variables studied, only contamination from adjacent vertebral marrow activity significantly affected the SUVmax of spinal cord. This contamination should be corrected for when reporting spinal cord FDG uptake. Lumbar thecal sac is not a valid reference for normalizing spinal cord FDG uptake.

PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain.

Despite the fact that appropriate social behaviors are vital to thriving in one's environment, little is understood of the molecular mechanisms controlling social behaviors or how social experience sculpts these signaling pathways. Here, we determine if Phosphodiesterase 11A (PDE11A), an enzyme that is enriched in the ventral hippocampal formation (VHIPP) and that breaks down cAMP and cGMP, regulates social behaviors. PDE11 wild-type (WT), heterozygous (HT), and knockout (KO) mice were tested in various social approach assays and gene expression differences were measured by RNA sequencing. The effect of social isolation on PDE11A4 compartmentalization and subsequent social interactions and social memory was also assessed. Deletion of PDE11A triggered age- and sex-dependent deficits in social approach in specific social contexts but not others. Mice appear to detect altered social behaviors of PDE11A KO mice, because C57BL/6J mice prefer to spend time with a sex-matched PDE11A WT vs. its KO littermate; whereas, a PDE11A KO prefers to spend time with a novel PDE11A KO vs. its WT littermate. Not only is PDE11A required for intact social interactions, we found that 1month of social isolation vs. group housing decreased PDE11A4 protein expression specifically within the membrane fraction of VHIPP. This isolation-induced decrease in PDE11A4 expression appears functional because social isolation impairs subsequent social approach behavior and social memory in a PDE11A genotype-dependent manner. Pathway analyses following RNA sequencing suggests PDE11A is a key regulator of the oxytocin pathway and membrane signaling, consistent with its pivotal role in regulating social behavior.

Phosphodiesterase 11A (PDE11A), Enriched in Ventral Hippocampus Neurons, is Required for Consolidation of Social but not Nonsocial Memories in Mice.

The capacity to form long-lasting social memories is critical to our health and survival. cAMP signaling in the ventral hippocampal formation (VHIPP) appears to be required for social memory formation, but the phosphodiesterase (PDE) involved remains unknown. Previously, we showed that PDE11A, which degrades cAMP and cGMP, is preferentially expressed in CA1 and subiculum of the VHIPP. Here, we determine whether PDE11A is expressed in neurons where it could directly influence synaptic plasticity and whether expression is required for the consolidation and/or retrieval of social memories. In CA1, and possibly CA2, PDE11A4 is expressed throughout neuronal cell bodies, dendrites (stratum radiatum), and axons (fimbria), but not astrocytes. Unlike PDE2A, PDE9A, or PDE10A, PDE11A4 expression begins very low at postnatal day 7 (P7) and dramatically increases until P28, at which time it stabilizes to young adult levels. This expression pattern is consistent with the fact that PDE11A is required for social long-term memory (LTM) formation during adolescence and adulthood. Male and female PDE11 knockout (KO) mice show normal short-term memory (STM) for social odor recognition (SOR) and social transmission of food preference (STFP), but no LTM 24 h post training. Importantly, PDE11A KO mice show normal LTM for nonsocial odor recognition. Deletion of PDE11A may impair memory consolidation by impairing requisite protein translation in the VHIPP. Relative to WT littermates, PDE11A KO mice show reduced expression of RSK2 and lowered phosphorylation of S6 (pS6-235/236). Together, these data suggest PDE11A is selectively required for the proper consolidation of recognition and associative social memories.

Rapid cessation of acute diarrhea using a novel solution of bioactive polyphenols: a randomized trial in Nicaraguan children.

Goal. We assessed the effectiveness of bioactive polyphenols contained in solution (LX) to restore normal bowel function in pediatric patients with acute diarrhea. Background. While providing oral rehydration solution (ORS) is standard treatment for diarrhea in developing countries, plant-derived products have been shown to positively affect intestinal function. If a supplement to ORS resolves diarrhea more rapidly than ORS alone, it is an improvement to current care. Study. In a randomized, double-blind, placebo-controlled cross-over study, 61 pediatric patients with uncontrolled diarrhea were randomized to receive either ORS + LX on day 1 and then ORS + water on day 2 (study arm) or ORS + water on day 1 and then ORS + LX on day 2 (control arm). Time to resolution and number of bowel movements were recorded. Results. On day 1, the mean time to diarrhea resolution was 3.1 h (study arm) versus 9.2 h (control arm) (p = 0.002). In the study arm, 60% of patients had normal stool at their first bowel movement after consumption of the phenolic redoxigen solution (LX). On day 2, patients in the study arm continued to have normal stool while patients in the control arm achieved normal stool within 24 h after consuming the test solution. Patients in the control arm experienced a reduction in the mean number of bowel movements from day 1 to day 2 after consuming the test solution (p = 0.0001). No adverse events were observed. Conclusions. Significant decreases in bowel movement frequency and rapid normalization of stool consistency were observed with consumption of this novel solution.