Reducing complication rates for repeat craniotomies in glioma patients: a single-surgeon experience and comparison with the literature.

BACKGROUND: There is a concern that glioma patients undergoing repeat craniotomies are more prone to complications. The study's goal was to assess if the complication profiles for initial and repeat craniotomies were similar, to determine predictors of complications, and to compare results with those in the literature. METHODS: A retrospective study was conducted of glioma patients (WHO grade II-IV) who underwent either an initial or repeat craniotomy performed by the senior author from 2012 until 2019. Complications were recorded by discharge, 30 days, and 90 days postoperatively. New neurologic deficits were recorded by 90 days postoperatively. Multivariate regression was performed to identify factors associated with complications. A meta-analysis was performed to identify rates of complications based on number of prior craniotomies. RESULTS: Within the cohort of 714 patients, 400 (56%) had no prior craniotomies, 218 (30.5%) had undergone 1 prior craniotomy, and 96 (13.5%) had undergone ≥ 2 prior craniotomies. There were 27 surgical and 10 medical complications in 30 patients (4.2%) and 19 reoperations for complications in 19 patients (2.7%) with no deaths by 90 days. Complications, reoperation rates, and new neurologic deficits did not differ based on number of prior craniotomies. On multivariate analysis, older age (OR1.5, 95%CI 1.0-2.2) and significant leukocytosis due to steroid use (OR12.6, 95%CI 2.5-62.9) were predictors of complications. Complication rates in the cohort were lower than rates reported in the literature. CONCLUSION: Contrary to prior reports in the literature, repeat craniotomies can be as safe as initial operations if surgeons implement best practices.

Relationship Between Physical Performance Testing Results and Peak Running Intensity During Professional Rugby League Match Play.

Duthie, GM, Thornton, HR, Delaney, JA, McMahon, JT, and Benton, DT. Relationship between physical performance testing results and peak running intensity during professional rugby league match play. J Strength Cond Res 34(12): 3506-3513, 2020-The purpose of this study was to examine the relationship between individual athletes' physical characteristics and both the peak running intensities and the decline in peak running intensities during competition. Twenty-two professional rugby league athletes (age; 24.1 ± 4.0 years, body mass; 101.4 ± 9.5 kg) underwent a series of physical testing procedures. Peak running intensity was determined using a moving average technique, applied to the speed (m·min), acceleration/deceleration (m·s), and metabolic power (W·kg) during competition, across 10 different durations. The power law relationship was then established, yielding an intercept and slope for the movement variables. Mixed linear models were then used to determine the relationship between physical characteristics and intercept and slope values. There were large, positive relationships between a player's maximal speed and both peak running speeds (effect size = 0.56, 90% confidence interval: 0.20-0.78) and metabolic power (0.57, 0.21-0.79) during competition. By contrast, there were large, negative associations between maximal speed and the rate of decline in running speed (-0.60, -0.81 to -0.27) and metabolic power (-0.65, -0.83 to -0.32) during competition. Similarly, there were negative associations between relative squat strength and the rate of decline in running speed (moderate: -0.41, -0.69 to -0.04) and metabolic power (large: -0.53, -0.77 to -0.17) during competition. The findings of this study demonstrate that a players running intensity during competition is underpinned by the individual athletes physiological qualities. Athletes demonstrating higher maximal speeds in testing were able to maintain higher running intensities over short durations but had a greater decrease in running intensity as duration increased.

Tc-99m-MAA lung shunt fraction before Y-90 radioembolization is low among patients with non-hepatocellular carcinoma malignancies.

OBJECTIVE: Lung shunt fraction studies using technetium-99 m macro aggregated albumin are routinely performed before yttrium-90 radioembolization regardless of underlying liver malignancy type. This study evaluates the role of lung shunt fraction studies in hepatocellular carcinoma compared to non-hepatocellular carcinoma liver tumors. METHODS: A single-institution retrospective analysis of all pre-yttrium-90 technetium-99 m macro aggregated albumin lung shunt fraction studies between November 2012 to March 2018 was performed. Patient variables including age, underlying malignancy, laboratory values, lung shunt fraction, and severity of liver disease were compared between hepatocellular carcinoma and non-hepatocellular carcinoma cases. RESULTS: A total of 734 technetium-99 m macro aggregated albumin studies were identified in 653 patients. Among these cases, the liver tumor was hepatocellular carcinoma in 368 (50.1%), colorectal cancer in 112 (15.3%), neuroendocrine tumor in 89 (12.1%), cholangiocarcinoma in 59 (8.0%), breast cancer in 27 (3.7%), and other metastatic malignancies in 79 (10.7%). The mean lung shunt fraction for non-hepatocellular carcinoma cases was 7.4%, which was significantly lower than the mean lung shunt fraction, 11.7%, for hepatocellular carcinoma cases (P = 0.0001). In only one non-hepatocellular carcinoma case was yttrium-90 radioembolization not pursued due to high lung shunt fraction (69.3%), wherein large scale shunting was grossly apparent on angiography in a patient with metastatic gastrointestinal stromal tumor. In comparison, the lung shunt fraction was too high to pursue radioembolization in 37 hepatocellular carcinoma cases (mean lung shunt fraction 35.1%). CONCLUSION: Lung shunt fraction appears low among patients with non-hepatocellular carcinoma liver malignancies. Further analysis examining the necessity of pre-Y90 technetium-99 m macro aggregated albumin lung shunt fraction studies in patients with non-hepatocellular carcinoma malignancies is warranted, since a consolidated yttrium-90 radioembolization without prior lung shunt fraction evaluation could reduce resource consumption, improve workflows, and patient access.

Morphologic mimickers of Cryptococcus occurring within inflammatory infiltrates in the setting of neutrophilic dermatitis: a series of three cases highlighting clinical dilemmas associated with a novel histopathologic pitfall.

A neutrophil-predominant inflammatory infiltrate in a cutaneous biopsy can be associated with a broad spectrum of diseases. Here we describe three cases showing a neutrophil-predominant dermal infiltrate admixed with abundant acellular bodies surrounded by capsule-like vacuolated spaces, which strikingly mimicked Cryptococcus. Two cases occurred within the settings of underlying hematologic malignancies; the third case was associated with immune dysregulation. Two patients were acutely ill in the medical intensive care unit. Fungal work-up, including cultures and multiple stains were negative. Because of clinical deterioration in these patients, transmission electron microscopy was pursued to definitively rule out fungal infection. In both cases, characteristics most compatible with autolysing human cells, not Cryptococcus, were identified. Chemotherapy and high-dose steroids were given, but both patients eventually succumbed to their diseases. To the best of our knowledge, these represent the first reported cases of autolysing human cells mimicking Cryptococcus organisms within neutrophilic infiltrates. They highlight the therapeutic dilemmas arising with histopathologic mimics, as well as the importance of thorough investigation to distinguish mimickers from true infectious organisms. We believe recognition of this microscopic pitfall will be useful to dermatopathologists faced with similar findings in the future, and may prevent unnecessary delay of appropriate therapy in acutely ill patients.

Collagenase-mediated tissue modeling of corneal ectasia and collagen cross-linking treatments.

PURPOSE: Corneal collagen cross-linking (CXL) is a method for modifying the natural history of keratoconus and other corneal ectatic diseases. The authors evaluated the use of collagenase for generating an experimental model of ectasia to evaluate the topographic effects of CXL interventions. METHODS: Nine human corneoscleral specimens unsuitable for transplantation were used. After epithelial debridement, mounting, and pressurization on an artificial anterior chamber, a solution of 10 mg/mL collagenase type II with 15% dextran was applied to five corneas for three hours. Three of these corneas subsequently underwent riboflavin/UV-A CXL. Scheimpflug-based tomography was performed before collagenase exposure, after collagenase exposure, and after CXL to evaluate changes in maximum axial curvature of the anterior surface (K(max)) at three IOP levels. Results were compared to four control eyes exposed to dextran alone. RESULTS: A statistically significant increase in K(max) was seen across all IOP levels in the collagenase group compared to the control group (+6.6 ± 1.1 diopters [D] and +0.3 ± 0.8 D, respectively, at physiological IOP). After CXL, K(max) decreased (-7.6 ± 2.0 D at physiological IOP). Anterior corneal aberrations increased after collagenase exposure and decreased after CXL. Light microscopy showed loss of normal stromal collagen architecture and localized edema after collagenase exposure. CONCLUSIONS: A method for generating topographic features of corneal ectasia in human tissue is demonstrated. No significant sensitivity of K(max) to IOP was observed. CXL caused regression of steepening and induced aberrations in this model, consistent with clinical trends. The model may be useful for testing modifications to standard CXL techniques.

Unusual ciliary abnormalities in three 9/11 response workers.

After the 9/11 terrorist attacks on the World Trade Center in New York in 2001, thousands of response workers were exposed to complex mixtures of toxins, pollutants, and carcinogens. Many developed illnesses involving the respiratory tract. We report unusual ultrastructural ciliary abnormalities in 3 response workers that corresponded to their respiratory and ciliary functional abnormalities. Each patient had respiratory cilia biopsies that were evaluated for motility and ultrastructural changes. Impaired ciliary motility was seen in 2 of the 3 patients. Each of the patients showed monomorphic ultrastructural abnormalities. Two of the patients showed identical triangular disarray of axonemal microtubules with peripheral doublets 1,4, and 7 forming the corners of the triangle and doublet 9 always more medially displaced than doublets 2, 3, 5, 6, and 8. Two workers had cilia in which axonemes were replaced by homogeneously dense cores. One of these also had cilia with triangular axonemes as previously described. The other had cilia with a geometric triangular to pentagonal shape. The ciliary abnormalities described here may represent a new class of primary ciliary dyskinesia in which abnormalities may have a genetic basis and a phenotypic expression that is prompted at the cellular level by local environmental conditions.

Granulomatous orbital inflammation associated with intraorbital titanium-impregnated acetate fiber.

Herein we report a 52-year-old man with subacute right-sided proptosis and diffuse intraconal enhancing abnormality on MRI. Orbital biopsy revealed granulomatous inflammation consistent with idiopathic orbital inflammatory syndrome (IOIS), or orbital pseudotumor. However, further examination under polarizing light microscopy also revealed acetate fiber fragments within the orbit. Prominent speckles within the acetate fibers were identified as titanium by Energy Dispersive X-ray Analysis (EDXA). Acetate impregnated with titanium (as a delustrant) is a common synthetic fiber used in textile and clothing manufacture. The mechanism for entrance into the orbit in this case is not known. Granulomatous idiopathic orbital inflammatory syndrome without local or systemic cause is an uncommon clinical entity, with less than 50 cases reported in the literature. Predominance of lacrimal gland (and thus superficial) involvement in granulomatous IOIS suggests the possibility of occult foreign body in such cases.

Fast food hamburgers: what are we really eating?

Americans consume about 5 billion hamburgers a year. It is presumed that most hamburgers are composed primarily of meat. The purpose of this study is to assess the content of 8 fast food hamburger brands using histologic methods. Eight different brands of hamburgers were evaluated for water content by weight and microscopically for recognizable tissue types. Glial fibrillary acidic protein (GFAP) staining was used to evaluate for brain tissue. Water content by weight ranged from 37.7% to 62.4% (mean, 49%). Meat content in the hamburgers ranged from 2.1% to 14.8% (median, 12.1%). The cost per gram of hamburger ranged from $0.02 to $0.16 (median, $0.03) and did not correlate with meat content. Electron microscopy showed relatively preserved skeletal muscle. A variety of tissue types besides skeletal muscle were observed including connective tissue (n = 8), blood vessels (n = 8), peripheral nerve (n = 8), adipose tissue (n = 7), plant material (n = 4), cartilage (n = 3), and bone (n = 2). In 2 hamburgers, intracellular parasites (Sarcocystis) were identified. The GFAP immunostaining was not observed in any of the hamburgers. Lipid content on oil-red-O staining was graded as 1+ (moderate) in 6 burgers and 2+ (marked) in 2 burgers. Fast food hamburgers are comprised of little meat (median, 12.1%). Approximately half of their weight is made up of water. Unexpected tissue types found in some hamburgers included bone, cartilage, and plant material; no brain tissue was present. Sarcocystis parasites were discovered in 2 hamburgers.

Ultrastructural abnormalities of respiratory cilia: a 25-year experience.

CONTEXT: Ciliary dyskinesia is a rare, but significant, cause of chronic respiratory infections, and transmission electron microscopy is a critical adjunct to making the diagnosis. OBJECTIVE: To investigate a single institution's experience with patients demonstrating abnormal ciliary ultrastructure. DESIGN: Retrospective clinicopathologic review of 278 bronchial or nasal turbinate brushings or biopsies from 1983 through 2007. RESULTS: There were 12 women and 9 men (mean age, 19.6 years; range, 1-54 years) with abnormal ciliary ultrastructure. Clinical history was unavailable in 3 patients, 15 (83%) of 18 patients presented with chronic or recurrent upper respiratory infections, and 3 (17%) presented with infertility. Seven (39%) of 18 patients had findings of Kartagener syndrome with situs inversus, dextrocardia, and bronchiectasis. Truncation or absence of inner or outer dynein arms occurred in 15 (71%) of 21 cases, and 5 (24%) revealed transposition defects with displacement of the central microtubules and peripheral doublets in 9 + 0 and 8 + 1 patterns. Radial spoke defects with microtubular disarray occurred in 4 (19%) of 21 cases. Compound cilia with multiple axonemes within a single outer sheath and supernumerary microtubules each occurred in 2 (10%) of the cases. Random ciliary orientation was also found in 2 (10%) of the cases, and dense granular basal body inclusions occurred in 1 case (5%). Multiple abnormalities occurred in 6 (29%) of the 21 cases. CONCLUSIONS: Most patients presented with chronic respiratory tract infections or infertility. Dynein arm defects, transposition defects, and radial spoke defects were the most commonly encountered abnormal findings. Less-frequent abnormal findings included compound cilia, supernumerary microtubules, and dense granular basal body inclusions.

Amantadine-associated corneal edema potentially irreversible even after cessation of the medication.

PURPOSE: To describe the clinical features of 3 patients with amantadine-associated corneal edema, including the histopathologic findings from 1 patient who underwent corneal transplantation for irreversible corneal edema. DESIGN: Interventional case series. PARTICIPANTS: Three patients who sought treatment at the authors' institution with abrupt-onset, bilateral, diffuse corneal edema associated with systemic amantadine use. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Visual acuity, corneal thickness, slit-lamp observations, and histopathologic findings. RESULTS: The duration of use of amantadine ranged from 2 months to 6 years before onset of corneal edema. Discontinuation of amantadine resulted in resolution of corneal edema in both eyes of 2 patients. A third patient underwent a full-thickness corneal transplantation, and subsequently, edema developed in the grafted cornea. Cessation of amantadine therapy in this patient resulted in resolution of corneal edema in both eyes, but the ungrafted corneal eventually decompensated and became edematous, requiring corneal transplantation. Histopathologic analysis of the cornea buttons showed significant loss of endothelial cells. CONCLUSIONS: Amantadine can cause corneal edema that begins a few months to several years after institution of therapy, and the edema can occur even in a corneal graft. Prolonged corneal edema in the setting of amantadine use can be irreversible. In cases of corneal edema without an obvious causative disease, the systemic medication list of the patient must be reviewed, and amantadine must be considered as a possible cause.

Applying morphologic techniques to evaluate hotdogs: what is in the hotdogs we eat?

Americans consume billions of hotdogs per year resulting in more than a billion dollars in retail sales. Package labels typically list some type of meat as the primary ingredient. The purpose of this study is to assess the meat and water content of several hotdog brands to determine if the package labels are accurate. Eight brands of hotdogs were evaluated for water content by weight. A variety of routine techniques in surgical pathology including routine light microscopy with hematoxylin-eosin-stained sections, special staining, immunohistochemistry, and electron microscopy were used to assess for meat content and for other recognizable components. Package labels indicated that the top-listed ingredient in all 8 brands was meat; the second listed ingredient was water (n = 6) and another type of meat (n = 2). Water comprised 44% to 69% (median, 57%) of the total weight. Meat content determined by microscopic cross-section analysis ranged from 2.9% to 21.2% (median, 5.7%). The cost per hotdog ($0.12-$0.42) roughly correlated with meat content. A variety of tissues were observed besides skeletal muscle including bone (n = 8), collagen (n = 8), blood vessels (n = 8), plant material (n = 8), peripheral nerve (n = 7), adipose (n = 5), cartilage (n = 4), and skin (n = 1). Glial fibrillary acidic protein immunostaining was not observed in any of the hotdogs. Lipid content on oil red O staining was graded as moderate in 3 hotdogs and marked in 5 hotdogs. Electron microscopy showed recognizable skeletal muscle with evidence of degenerative changes. In conclusion, hotdog ingredient labels are misleading; most brands are more than 50% water by weight. The amount of meat (skeletal muscle) in most brands comprised less than 10% of the cross-sectional surface area. More expensive brands generally had more meat. All hotdogs contained other tissue types (bone and cartilage) not related to skeletal muscle; brain tissue was not present.

Ultra-late antibody-mediated rejection 30 years after a living-related renal allograft.

Antibody-mediated renal allograft rejection has become increasingly recognized and more clearly defined through the use of flow cytometry cross-matching and the deposition of C4d in renal allograft biopsies. All of the cases reported thus far have developed an antibody within 10 years of transplantation, and many lacked HLA and/or donor specificity. The present patient developed an anti-HLA donor-specific antibody between the 22nd and 30th year after a living-related renal transplant. At the 30th year post-transplantation, she experienced a rise in the serum creatinine from 0.7 to 1.9 mg/dL associated with transplant biopsy C4d deposition in peritubular capillaries and glomeruli. After the replacement of azathioprine with mycophenolate mofetil, and six apheresis treatments followed by two infusions of IVIG, the renal function stabilized at 1.9 mg/dL, 33 years after transplantation. Antibody-mediated rejection must be considered as a possible cause or renal allograft dysfunction at all time periods after transplantation.

Evidence of specialized conduction cells in human pulmonary veins of patients with atrial fibrillation.

UNLABELLED: Specialized Conducting Cells in Human PV. INTRODUCTION: Depolarizations similar to those from the sinus node have been documented from the pulmonary veins after isolation procedures. We assessed the hypothesis that sinus node-like tissue is present in the pulmonary veins of humans. METHODS AND RESULTS: Pulmonary vein tissue was obtained from five autopsies (four individuals with a history of atrial fibrillation and one without a history of atrial arrhythmias) and five transplant heart donors. Autopsy veins were fixed in formaldehyde and processed for light microscopy to identify areas having possible conductive-like tissue. Areas requiring additional study were extracted from paraffin blocks and reprocessed for electron microscopy. Donor specimens were fixed in formaldehyde for histologic sections and glutaraldehyde for electron microscopy. Myocardial cells with pale cytoplasm were identified by light microscopy in 4 of the 5 autopsy subjects. Electron microscopy confirmed the presence of P cells, transitional cells, and Purkinje cells in the pulmonary veins of these cases. CONCLUSION: Our report is the first to show the presence of P cells, transitional cells, and Purkinje cells in human pulmonary veins. Whether these cells are relevant in the genesis of atrial fibrillation requires further study.

Demonstration of immune complex deposits using fluorescence microscopy of hematoxylin and eosin-stained sections of Hollande's fixed renal biopsies.

A new method that may be useful in the evaluation of renal biopsies is described using fluorescence microscopy on standard hematoxylin and eosin-stained sections of kidney tissue fixed in Hollande's fixative. We describe brightly fluorescing immune complex deposits within glomerular basement membranes and mesangial matrices that correlate well with the results of standard direct immunofluorescence on frozen tissue and electron microscopy. In a blind analysis of 261 consecutive renal biopsies, we determine that this method has diagnostic utility for identification of immune complex glomerulonephritis and significantly extends the usefulness of standard histologic preparations before the use of special stains or procedures.

Histologic evaluation of posterior cruciate ligaments from osteoarthritic knees.

It is controversial whether posterior cruciate ligament-retaining or posterior cruciate ligament-sacrificing (-substituting) implants should be used in total knee arthroplasty. The use of posterior cruciate ligament-retaining implants implies that the residual ligament is functional, and presumably normal, but few studies have been conducted to elucidate the histologic appearance of the posterior cruciate ligament taken from osteoarthritic knees. The purposes of the current study were (1) to evaluate the histologic appearance of posterior cruciate ligaments excised from osteoarthritic knees during primary total knee arthroplasty and to compare their appearance with posterior cruciate ligaments from knees of cadavers that were not operated on; and (2) to determine whether a correlation exists between the histologic appearance of the posterior cruciate ligament and the clinical status of the patients studied. Twenty-six posterior cruciate ligament specimens from patients with osteoarthritis and four specimens from cadavers were evaluated with the use of light and electron microscopy. Posterior cruciate ligaments from osteoarthritic knees showed greater degeneration than those from cadavers by light microscopy. Age greater than 60 years was associated with decreased collagen diameter in posterior cruciate ligaments from osteoarthritic knees as determined by electron microscopy. With the number of specimens available, the authors could not find a significant correlation between tibiofemoral alignment and mean collagen diameter or percentage of collagen occupancy. The extent of tissue degeneration of the posterior cruciate ligament could not be predicted by clinical findings. Additional studies identifying the mechanical competency of the posterior cruciate ligament in osteoarthritis would be valuable.

Eosinophilic intranuclear inclusion bodies in a melanocytic nevus.

We report a case of eosinophilic or hyaline true intranuclear inclusion bodies in a melanocytic nevus. Although intranuclear pseudoinclusions are frequently found in melanocytic nevi, true intranuclear inclusions are rare. The true intranuclear nature of the inclusions in our case was confirmed with ultrastructural examination. With reverse transcriptase in situ polymerase chain reaction (RT in situ PCR) analysis, eosinophilic bodies stained positive for molluscum-specific primers. This result suggests that such inclusions may be related to molluscum viral infection of melanocytes.