Comparative histopathological analysis of age-associated intervertebral disc degeneration in CD-1 and C57BL/6 mice: Anatomical and sex-based differences.

Background: Intervertebral disc (IVD) degeneration is a major contributor to back pain and disability. The cause of IVD degeneration is multifactorial, with no disease-modifying treatments. Mouse models are commonly used to study IVD degeneration; however, the effects of anatomical location, strain, and sex on the progression of age-associated degeneration are poorly understood. Methods: A longitudinal study was conducted to characterize age-, anatomical-, and sex-specific differences in IVD degeneration in two commonly used strains of mice, C57BL/6 and CD-1. Histopathological evaluation of the cervical, thoracic, lumbar, and caudal regions of mice at 6, 12, 20, and 24 months of age was conducted by two blinded observers at each IVD for the nucleus pulposus (NP), annulus fibrosus (AF), and the NP/AF boundary compartments, enabling analysis of scores by tissue compartment, summed scores for each IVD, or averaged scores for each anatomical region. Results: C57BL/6 mice displayed mild IVD degeneration until 24 months of age; at this point, the lumbar spine demonstrated the most degeneration compared to other regions. Degeneration was detected earlier in the CD-1 mice (20 months of age) in both the thoracic and lumbar spine. In CD-1 mice, moderate to severe degeneration was noted in the cervical spine at all time points assessed. In both strains, age-associated IVD degeneration in the thoracic and lumbar spine was associated with increased histopathological scores in all IVD compartments. In both strains, minimal degeneration was detected in caudal IVDs out to 24 months of age. Both C57BL/6 and CD-1 mice displayed sex-specific differences in the presentation and progression of age-associated IVD degeneration. Conclusions: These results showed that the progression and severity of age-associated degeneration in mouse models is associated with marked differences based on anatomical region, sex, and strain. This information provides a fundamental baseline characterization for users of mouse models to enable effective and appropriate experimental design, interpretation, and comparison between studies.

FDG PET/CT and thyroid biopsy leads to neurosarcoidosis diagnosis.

We present a unique case of neurosarcoidosis diagnosed based on thyroid biopsy and FDG PET (Fluorodeoxyglucose positron emission tomography) imaging. A patient presented for a second opinion after being placed in hospice for rapidly progressing dementia, presumed to be due to Creutzfeldt Jakob disease despite negative workup and was unable to perform activities of daily life or communicate with his wife. The patient underwent a workup including whole-body FDG PET, which showed hypermetabolic lymph nodes as well as a hypermetabolic nodule in the thyroid. Biopsy of the lymph nodes was nondiagnostic, but the thyroid biopsy tissue yielded a diagnosis of sarcoid. After ruling out other causes and reviewing the tissue pathology, the patient was diagnosed with systemic sarcoidosis with neurological involvement and started on infliximab with rapid improvement.

Iatrogenic Arteriovenous Fistula Following Routine Venipuncture in an Adult Without Coagulopathy: An Uncommon Consequence of a Common Procedure.

Background: According to Tonnessen BH (2011),1 iatrogenic arteriovenous (AV) fistulas in adults most commonly occur due to endovascular access and procedures. Rarely, AV fistulas have been reported in low birth weight neonates following repeating venipuncture. This complication is extremely uncommon in adults, but has been reported after routine venipuncture for blood transfusion. Case presentation: We report the case of an elderly female patient who presented to the office for evaluation of left upper extremity swelling, ecchymosis, and dilated vessels after routine venipuncture at an outpatient laboratory. She was subsequently found to have an acquired AV fistula from her left cephalic vein to a small branch artery. Conclusion: This case demonstrates the rare but relevant risk in routine venipuncture and may underscore the benefit of using ultrasound guidance in high-risk populations, such as patients with coagulopathies, or thin, fragile veins, like the elderly or neonates.

Selective enhancement of neural coding in V1 underlies fine-discrimination learning in tree shrew.

Visual discrimination improves with training, a phenomenon that is thought to reflect plastic changes in the responses of neurons in primary visual cortex (V1). However, the identity of the neurons that undergo change, the nature of the changes, and the consequences of these changes for other visual behaviors remain unclear. We used chronic in vivo 2-photon calcium imaging to monitor the responses of neurons in the V1 of tree shrews learning a Go/No-Go fine orientation discrimination task. We observed increases in neural population measures of discriminability for task-relevant stimuli that correlate with performance and depend on a select subset of neurons with preferred orientations that include the rewarded stimulus and nearby orientations biased away from the non-rewarded stimulus. Learning is accompanied by selective enhancement in the response of these neurons to the rewarded stimulus that further increases their ability to discriminate the task stimuli. These changes persist outside of the trained task and predict observed enhancement and impairment in performance of other discriminations, providing evidence for selective and persistent learning-induced plasticity in the V1, with significant consequences for perception.

Abnormal findings on abdominopelvic cross-sectional imaging in patients with microscopic colitis: a retrospective, multicenter study.

OBJECTIVES: Patients with microscopic colitis may have subtle macroscopic findings on colonoscopy such as erythema, edema, or altered vascular pattern; however, radiographic abnormalities on cross-sectional imaging have not been investigated. We aimed at identifying the abdominopelvic radiographic abnormalities in patients with microscopic colitis, as well as possible correlation with endoscopic findings and the need for extended duration of treatment. MATERIALS AND METHODS: This was a retrospective study of patients with biopsy-proven microscopic colitis at two tertiary centers between 1 January 2010 and 30 April 2020. Patients underwent computed tomography scan or magnetic resonance imaging within 30 days of a diagnostic flexible sigmoidoscopy or colonoscopy. Patients with colon ischemia and other causes of colitis were excluded. Radiographic abnormalities from imaging reports included bowel wall thickening, mucosal hyperenhancement and mesenteric fat stranding. Univariate and multivariable logistic regression models were used to identify predictors of radiographic abnormalities. RESULTS: 498 patients with microscopic colitis underwent abdominopelvic cross-sectional imaging within 30 days of flexible sigmoidoscopy/colonoscopy. Lymphocytic colitis was diagnosed in 54.6% of patients, and collagenous colitis in 45.4%. Endoscopic and radiographic abnormalities were identified in 16.1% and 12.4% of patients, respectively. Radiographic abnormalities were associated with the need for budesonide therapy (p = .029) and budesonide therapy long-term (p = .0028). Budesonide therapy long-term (p = .047) was associated with radiographic abnormalities in multivariate analysis. CONCLUSIONS: Radiographic abnormalities may be present on abdominopelvic cross-sectional imaging in a minority of patients with biopsy-proven microscopic colitis, suggesting cross-sectional imaging has low clinical value in the evaluation and treatment of this disease.

Emergency radiologic approach to sinus disease.

Sinus disease is commonly encountered, especially in the acute care setting. Imaging can support a diagnosis of sinusitis, help identify an etiology, and delineate intracranial and extracranial complications. Suspicion of complicated rhinosinusitis is an indication for contrast-enhanced computed tomography or magnetic resonance imaging. It is important for radiologists to be familiar with patient risk factors that predispose to uncommon but aggressive forms of sinus disease such as invasive fungal sinusitis. Lastly, many conditions, ranging from benign to malignant, can mimic rhinosinusitis clinically and on imaging. Radiologists can help by recognizing these entities and facilitating appropriate referral and follow-up. This article reviews the breadth of sinus disease commonly encountered in the emergency setting, potential complications, and mimics.

Smooth Muscle Conditions of the Chest: A Clinical, Radiologic, and Pathologic Review.

Smooth muscle conditions of the chest have diverse clinical and imaging manifestations and may involve nearly every thoracic structure. Differentiation among these conditions requires the integration of clinical, radiologic, and histopathologic data. Histologic examination in conjunction with immunohistochemistry is essential for differentiation from other spindle cell neoplastic mimics. Familiarity with these entities will ensure the inclusion of smooth muscle conditions in the differential diagnosis of thoracic soft tissue lesions and potentially guide the clinician in appropriate management. We review the clinical, imaging, and histopathologic features of thoracic smooth muscle-related conditions organized by the anatomic structures affected.

Thoracic endometriosis presenting as a catamenial hemothorax with discordant video-assisted thoracoscopic surgery.

Thoracic endometriosis is uncommon and may be overlooked, resulting in a delay in diagnosis. We describe the case of a 47-year-old woman presenting with acute onset pleuritic pain and hemothorax secondary to this rare entity. The diagnosis of thoracic endometriosis is driven by a compatible clinical history coupled with supportive imaging and immunohistochemical findings. Imaging features lack specificity, however, computed tomography and magnetic resonance imaging play an important role in identifying pleural/diaphragmatic involvement and excluding other more common diseases. Immunohistochemical pleural fluid analysis can confirm the presence of hormone receptor-positive endometrial glands and stroma. We illustrate a few potential diagnostic pitfalls, specifically the inconsistency in diagnostic yield of video-assisted thoracoscopic surgery/thoracentesis and the variable temporal association of patients' symptoms and pathology with menstruation. Prompt identification of thoracic endometriosis is important as it enables early institution of therapy and limits future complications.

Transcriptional profiling of the murine intervertebral disc and age-associated changes in the nucleus pulposus.

Purpose/Aim: The intervertebral disc (IVD) is composed of cell types whose subtle phenotypic differences allow for the formation of distinct tissues. The role of the nucleus pulposus (NP) in the initiation and progression of IVD degeneration is well established; however, the genes and pathways associated with NP degeneration are poorly characterized.Materials and Methods: Using a genetic strategy for IVD lineage-specific fluorescent reporter expression to isolate cells, gene expression and bioinformatic analysis was conducted on the murine NP at 2.5, 6, and 21 months-of-age and the annulus fibrosus (AF) at 2.5 and 6 months-of-age. A subset of differentially regulated genes was validated by qRT-PCR.Results: Transcriptome analysis identified distinct profiles of NP and AF gene expression that were remarkably consistent at 2.5 and 6 months-of-age. Prg4, Cilp, Ibsp and Comp were increased >50-fold in the AF relative to NP. The most highly enriched NP genes included Dsc3 and Cdh6, members of the cadherin superfamily, and microRNAs mir218-1 and mir490. Changes in the NP between 2.5 and 6 months-of-age were associated with up-regulation of molecular functions linked to laminin and Bmp receptor binding (including up-regulation of Bmp5 & 7), with the most up-regulated genes being Mir703, Shh, and Sfrp5. NP degeneration was associated with molecular functions linked to alpha-actinin binding (including up-regulation of Ttn & Myot) and cytoskeletal protein binding, with the overall most up-regulated genes being Rnu3a, Snora2b and Mir669h.Conclusions: This study provided insight into the phenotypes of NP and AF cells, and identified candidate pathways that may regulate degeneration.

The role of PPARγ in childhood obesity-induced fractures.

Globally, obesity is on the rise with ~ 30% of the world's population now obese, and childhood obesity is following similar trends. Childhood obesity has been associated with numerous chronic conditions, including musculoskeletal disorders. This review highlights the effects of childhood adiposity on bone density by way of analyzing clinical studies and further describing two severe skeletal conditions, slipped capital femoral epiphysis and Blount's disease. The latter half of this review discusses bone remodeling and cell types that mediate bone growth and strength, including key growth factors and transcription factors that help orchestrate this complex pathology. In particular, the transcriptional factor peroxisome proliferator-activated receptor gamma (PPARγ) is examined as it is a master regulator of adipocyte differentiation in mesenchymal stem cells (MSCs) that can also influence osteoblast populations. Obese individuals are known to have higher levels of PPARγ expression which contributes to their increased adipocyte numbers and decreased bone density. Modulating PPAR*gamma* signaling can have significant effects on adipogenesis, thereby directing MSCs down the osteoblastogenesis pathway and in turn increasing bone mineral density. Lastly, we explore the potential of PPARγ as a druggable target to decrease adiposity, increase bone density, and be a treatment for children with obesity-induced bone fractures.

Allogeneic mesenchymal stem cells for treatment of severe burn injury.

The most important determinant of survival post-burn injury is wound healing. For decades, allogeneic mesenchymal stem cells (MSCs) have been suggested as a potential treatment for severe burn injuries. This report describes a patient with a severe burn injury whose wounds did not heal with over 18 months of conventional burn care. When treated with allogeneic MSCs, wound healing accelerated with no adverse treatment complications. Wound sites showed no evidence of keloids or hypertrophic formation during a 6-year follow-up period. This therapeutic use of allogeneic MSCs for large non-healing burn wounds was deemed safe and effective and has great treatment potential.

Earlier tracheostomy and percutaneous endoscopic gastrostomy in patients with hemorrhagic stroke: associated factors and effects on hospitalization.

OBJECTIVE: Existing literature supports benefits of early tracheostomy and percutaneous endoscopic gastrostomy (PEG) in certain patient populations. The aim of this study was to review tracheostomy and PEG placement data in patients with hemorrhagic stroke in order to identify factors associated with earlier placement and to evaluate outcomes. METHODS: The authors performed a retrospective review of consecutive patients treated for hemorrhagic stroke between June 1, 2011, and June 1, 2015. Data were analyzed by logistic and multiple linear regression. RESULTS: Of 240 patients diagnosed with hemorrhagic stroke, 31.25% underwent tracheostomy and 35.83% underwent PEG tube placement. Factors significantly associated with tracheostomy and PEG included the presence of pneumonia on admission and subarachnoid hemorrhage. Earlier tracheostomy was significantly associated with shorter ICU length of stay; earlier tracheostomy and PEG placement were associated with shorter overall hospitalization. Timing of tracheostomy and PEG was not significantly associated with patient survival or the incidence of complications in this population. CONCLUSIONS: This study identified patient risk factors associated with increased likelihood of tracheostomy and PEG in patients with hemorrhagic stroke who were critically ill. Additionally, we found that the timing of tracheostomy was associated with length of ICU stay and overall hospital stay, and that the timing of PEG was associated with overall length of hospitalization. Complication rates related to tracheostomy and PEG in this population were minimal. This retrospective data set supports some benefit to earlier tracheostomy and PEG placement in this population and justifies the need for further prospective study.

Obesity and Insulin Resistance, Not Polycystic Ovary Syndrome, Are Independent Predictors of Bone Mineral Density in Adolescents and Young Women.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders that affects females of reproductive age. The characteristic features of PCOS individually have opposing effects on bone mineral density (BMD); however, their cumulative effect on BMD has not been clearly defined. Adolescence and young adulthood span a crucial period in achieving peak bone mass. Thus, a better understanding of the impact of PCOS on BMD in this age group is needed. OBJECTIVES: To determine whether BMD is different between young females with PCOS and controls and to identify factors that influence BMD in this population. METHODS: Data from four cross-sectional studies with a total of 170 females aged 12-25 years with PCOS (n = 123) and controls (n = 47) with a wide range of BMIs (18.7-53.4 kg/m2) were analyzed. Participants had fasting glucose, insulin, and free and total testosterone concentrations measured. HOMA-IR was calculated. Whole-body BMD was assessed by dual-energy X-ray absorptiometry. Multiple regression analysis for predicting BMD included PCOS status, menstrual age, obesity, HOMA-IR, and free testosterone. RESULTS: HOMA-IR and total and free testosterone were significantly higher in PCOS compared to controls but there was no difference in BMD z-score between PCOS (0.8 ± 1.0) and controls (0.6 ± 1.0) (p = 0.36). Obesity (p = 0.03) and HOMA-IR (p = 0.02) were associated with BMD z-score. CONCLUSIONS: Obesity status and insulin resistance, but not PCOS status, were each independently associated with BMD in adolescents and young women who spanned a wide range of BMIs.

Burn injury and multiple sclerosis: A retrospective case-control study.

OBJECTIVES: The purpose of this study was to determine whether having a previous diagnosis of multiple sclerosis (MS) changed acute care needs in burn-injured patients. METHODS: This was a retrospective case-control study that included adult (aged ≥18years) patients with an acute burn injury. Control patients were matched with eleven patients with a history of MS at a 4:1 ratio. Outcomes included fluid resuscitation volumes, temperature, heart rate, mean arterial pressure, in-hospital complications, and hospital length of stay (LOS). RESULTS: There were fifty-five patients included and of those, eleven had a documented history of MS. Fluid resuscitation volumes, temperature, heart rate, and mean arterial pressure were similar between groups during the resuscitation period (p>0.05). LOS was similar between both groups (12, IQR: 2-17 vs. median 16, IQR: 12-21; p=0.090). However, when normalized to % TBSA burn, patients with MS had a significantly higher median LOS/% TBSA burned (1.2, IQR: 0.7-2.0 vs. 2.1, IQR: 1.1-7.1; p=0.031). CONCLUSIONS: Patients with concurrent burn injuries and MS have a significantly longer LOS/% TBSA burn suggesting that more time is required to heal their wounds. Surprisingly, there were no other significant differences in the after the burn acute phase between these two cohorts.

Contributors to the length-of-stay trajectory in burn-injured patients.

OBJECTIVES: Burn patients have a highly variable length-of-stay (LOS) due to the complexity of the injury itself. The LOS for burn patients is estimated as one day per percent total body surface area (TBSA) burn. To focus care expectation and prognosis we aimed to identify key factors that contribute to prolonged LOS. METHODS: This was a retrospective cohort-study (2006-2016) in an adult burn-centre that included patients with ≥10% TBSA burn. Patients were stratified into expected-LOS (<2 days LOS/%TBSA) and longer-than-expected-LOS (≥2 days LOS/%TBSA). We assessed demographics, comorbidities, and in-hospital complications. Logistic regression and propensity matching was utilized. RESULTS: Of the 583 total patients, 477 had an expected-LOS whereas 106 a longer-than-expected-LOS. Non-modifiable factors such as age, 3rd degree TBSA%, inhalation injuries and comorbidities were greater in the exceeded LOS patients. Subsequent matched analysis revealed factors like number of procedures performed, days ventilated and in-hospital complications (bacteremia, pneumonia, sepsis, graft loss, and respiratory failure) were significantly increased in the longer-than-expected-LOS group. CONCLUSIONS: Progress has been made to update the conventional one day/%TBSA to better aid health care providers in giving appropriate outcomes for patients and their families and to supply intensive care units with valuable data to assess quality of care and to improve patient prognosis.

Impact of the 2016 US presidential election on OCD symptom presentation: A case illustration.

A recent survey of Americans found that the majority experienced stress during and after the 2016 United States presidential election. Psychosocial, environmental stressors can have a unique impact on symptom presentation in mental health disorders. This manuscript details a case illustration of an individual whose symptoms of obsessive-compulsive disorder were directly linked to the election, as well as how these symptoms were addressed via treatment with intensive exposure and response prevention.