Cardiovascular disease associated with methamphetamine use: a review.

Methamphetamine abuse is a global epidemic associated with a wide-ranging array of adverse effects on the cardiovascular system including dilated cardiomyopathy, malignant and benign arrhythmias, coronary vasospasm, and atherosclerotic coronary artery disease. While the acute behavioral manifestations of amphetamine abuse are the most easily clinically identified, cardiovascular toxicity is common in this patient population and should be considered in this setting due to its high morbidity and mortality. The specific mechanisms for amphetamine cardiotoxicity have not been fully established, but new research implicates activation of several cellular targets including Sigma-1 receptors and trace amine-associated receptor 1 (TAAR1) leading to a myriad of negative downstream effects including increased reactive oxygenating species (ROS), mitochondrial dysfunction, and modulations of intracellular calcium. Additional pathologic effects are mediated by increased circulating catecholamines, which when chronically activated have well-established adverse effects on the cardiovascular system. In this article, we present a case report followed by a current review of the epidemiology, pathophysiology, diagnosis, and treatment modalities of amphetamine-induced cardiovascular disease.

Interobserver reproducibility of the diagnosis of differentiated exophytic vulvar intraepithelial lesion (DEVIL) and the distinction from its mimics.

AIMS: Most vulvar squamous cell carcinomas are human papillomavirus (HPV)-associated or TP53-mutant. A third category of HPV-independent TP53-wild-type lesions is uncommon and not fully understood. Differentiated exophytic vulvar intraepithelial lesion (DEVIL) has been characterised as a precursor of this latter category. The reproducibility of the diagnosis of DEVIL and its distinction from lesions with overlapping morphology has not been studied. Our aim was to establish the interobserver agreement in the diagnosis of DEVIL and its distinction from neoplastic and reactive conditions of the vulva on haematoxylin and eosin evaluation. METHODS AND RESULTS: A set of 35 slides was evaluated by eight reviewers (two trainees and six practising gynaecological pathologists). The set included DEVIL, condyloma, established vulvar precursors [high-grade squamous intraepithelial lesion (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN)] with superimposed acanthosis or verruciform growth, lichen simplex chronicus (LSC), and psoriasis. Kappa (κ) values were calculated. Overall, interobserver agreement was moderate (κ = 0.56), improving to substantial (κ = 0.7) when evaluation was performed by practising pathologists. Agreement was strong for the diagnosis of HSIL (κ = 0.88), and substantial for the diagnosis of DEVIL (κ = 0.61), condyloma (κ = 0.79), and LSC (κ = 0.72). Agreement was moderate for the diagnosis of dVIN (κ = 0.59) and psoriasis (κ = 0.53). Perfect agreement (6/6) among practising pathologists was observed in 43% of cases, and majority agreement (5/6 or 4/6) was observed in 48% of cases. CONCLUSIONS: Reproducibility in the diagnosis of verruciform vulvar lesions, including the novel DEVIL, is acceptable overall. Reproducibility is higher for well-known lesions such as HSIL and condyloma than for more challenging diagnoses such as DEVIL, dVIN, and psoriasis. Agreement is higher among practising gynaecological pathologists, suggesting that training and experience improve reproducibility. Our findings support the inclusion of DEVIL as a diagnostic entity in the classification of vulvar squamous lesions.

Correlation of p16 immunostaining in cell-blocks with corresponding tissue specimens for squamous cell carcinomas of the oropharynx.

OBJECTIVE: The goal of this study was to evaluate the performance of p16 staining in cell-blocks vs tissue specimens as a surrogate marker for human papillomavirus (HPV) status in oropharyngeal squamous cell carcinomas. METHODS: Head and neck squamous cell carcinoma cases presenting as a neck mass with a p16 result on cytology and corresponding tissue specimens (1 January 2014 to 30 June 1920) were included in the study. The following were assessed from cell-block material: number of tumour clusters, percentage of tumour cells with p16 staining, and presence of staining in clusters vs single cells. Results were compared to tissue p16 status. Results of any other ancillary HPV testing were also noted. RESULTS: Forty-two head and neck squamous cell carcinoma neck metastases (35 oropharyngeal, five non-oropharyngeal, and 2 unknown primaries) were identified. The p16 staining pattern in cell-blocks was seen in single cells (27.6%), clusters (44.8%), or both (27.6%). The percentage of tumour cells staining for p16 in cell-blocks was much lower than in corresponding tissue specimens. There were four false negatives and one false positive (concurrent HPV DNA polymerase chain reaction testing was positive in cytology and surgical material). CONCLUSIONS: Compared to tissue, the cut-off for p16 interpretation in cell-blocks is substantially lower and staining may be present in single cells or clusters. In 96.9% of cases, any p16 staining in cell-blocks correlated with positive p16 staining in surgical specimens. However, a negative or discrepant p16 result on cell-block should prompt confirmatory HPV studies, as false negative p16 staining in cell-blocks is high.

Potential Diagnostic Pitfalls in Evaluating Immunohistochemistry for Cervical Myofibroblastomas.

Cervicovaginal myofibroblastoma (CVM) is a rare benign mesenchymal tumor of the lower female genital tract that shows chromosomal loss of 13q14 (RB1 gene located in this region). The aim of this study was to investigate the utility of immunohistochemistry (IHC) for desmin, CD34, and Rb in diagnosing CVM. All cervical polyps diagnosed from July 2016 to July 2017 were retrospectively reviewed. Cases showing morphologic myofibroblastic differentiation were evaluated by IHC for desmin, CD34, and Rb. Desmin and CD34 staining was recorded as positive or negative. Rb nuclear staining was graded as follows: 0 (<10%), 1 (10%-25%), 2 (>25%-50%), 3 (>50%-75%), or 4 (>75%). Intact nuclear expression of Rb in endothelial cells served as an internal positive control. IHC was performed on 76 cases with 14 excluded from the final cohort due to poor Rb internal control. A total of 61/62 (98.4%) cases were positive for desmin and CD34 with the following Rb distribution: grade 0 (n=53, 86.9%), grade 1 (n=5, 8.2%), grade 2 (n=2, 3.3%), and grade 3 (n=1, 1.6%). One case negative for desmin and CD34 showed grade 3 Rb staining. Upon rereview of the histology, 7/175 cases (4%) were morphologically and immunohistochemically compatible with CVM (desmin and CD34+ grade 0 Rb staining). CVM is a rare and under-recognized entity (4% of cervical polyps) for which morphology remains the mainstay of diagnosis. IHC reliance serves as a potential diagnostic pitfall as 86.9% of cases showing myofibroblastic differentiation demonstrated the staining pattern of desmin and CD34 positivity and Rb deficiency.

The utility of the Milan System as a risk stratification tool for salivary gland fine needle aspiration cytology specimens.

OBJECTIVE: To perform a retrospective investigation of our institutional experience with salivary gland fine needle aspirations (FNA) through the framework of The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and assess the risks of neoplasm and malignancy for each diagnostic category. METHODS: All salivary gland FNAs performed from January 2009 to December 2016 were retrospectively categorised according to the MSRSGC. When available, pre-operative cytological results were correlated with subsequent histological follow-up. RESULTS: In total, 893 FNAs were reviewed. The specimens were retrospectively classified as nondiagnostic (ND: 13.5%), non-neoplastic (NN: 16.1%), atypia of undetermined significance (AUS: 10.8%), benign neoplasm (BN: 34.9%), salivary gland neoplasm of uncertain malignant potential (SUMP: 8.2%), suspicious for malignancy (SM: 2.7%) and malignant (M: 13.8%). Histological follow-up was available for 429 cases (48%); the majority (68.1%) were benign. The risks of neoplasm and malignancy for each category were as follows: ND: 64.5%, 16.1%; NN: 42.9%, 17.9%; AUS: 79.6%, 30.6%; BN: 100%, 2.2%; SUMP: 100%, 46.6%; SM: 94.7%, 78.9%; and M: 100%, 98.5%. CONCLUSIONS: The MSRSGC is a useful classification scheme for stratifying salivary gland lesions according to their associated risk of malignancy and guiding clinicians toward appropriate management. Diagnostic pitfalls are seen in a small proportion of cases and a multidisciplinary approach for assessing salivary gland pathology is essential in their evaluation.

The pharmacokinetics, safety, and tolerability of single, high-strength doses of fluticasone propionate and fluticasone propionate/salmeterol delivered via a novel multidose dry powder inhaler in adolescents and adults with persistent asthma.

OBJECTIVE: Characterize fluticasone propionate (Fp) and combination fluticasone propionate and salmeterol (FS) pharmacokinetic and safety profiles, delivered via a novel, inhalation-driven, multidose dry powder inhaler (MDPI). METHODS: This multicenter, open-label, four-period crossover, single-dose study randomized patients aged ≥12 years with persistent asthma to Fp MDPI 200 mcg, FS MDPI 200/12.5 mcg, Fp dry powder inhaler (DPI) 500 mcg (250 mcg × 2 inhalations), or FS DPI 500/50 mcg. Blood samples for determination of Fp and salmeterol pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, tmax, and t½ were collected predose through 36 h postdose (14 time points). Safety assessments comprised adverse events, vital signs, and physical examinations. The institutional review board approved the study protocol. RESULTS: The pharmacokinetic analysis set and safety population each included 40 patients. Fp systemic exposure (Cmax, AUC0-t, and AUC0-inf) was highest for Fp DPI 500 mcg and similar for Fp MDPI 200 mcg, FS MDPI 200/12.5 mcg, and FS DPI 500/50 mcg. Fp geometric mean t½ values were similar across treatments. Salmeterol Cmax was 20% lower and AUC0-t and AUC0-inf were approximately 50% lower with FS MDPI versus FS DPI. Median tmax and geometric mean t½ were similar between FS MDPI and FS DPI. Adverse events were similar across treatments with no relevant changes in vital signs, physical examinations, or hematology test results. CONCLUSIONS: Fp MDPI and FS MDPI produced similar or lower systemic exposure to Fp and salmeterol, despite lower doses, versus conventional DPI devices, suggesting improved efficiency due to formulation and device differences.

Randomized, dose-ranging study of a fluticasone propionate multidose dry powder inhaler in adolescents and adults with uncontrolled asthma not previously treated with inhaled corticosteroids.

OBJECTIVE: A novel, inhalation-driven, multidose dry powder inhaler (MDPI) eliminates the need to coordinate actuation with inhalation. To characterize dose response, efficacy, and safety of fluticasone propionate (Fp) MDPI, a dose-ranging study was conducted with placebo and active comparators. METHODS: This 12-week, double-blind, parallel-group study randomized patients aged ≥12 years with uncontrolled persistent asthma not previously treated with inhaled corticosteroid therapy (N = 622) to twice-daily treatment with Fp MDPI (12.5, 25, 50, or 100 µg), placebo MDPI, or open-label Fp dry powder inhaler (DPI) 100 µg. The primary efficacy endpoint was change from baseline over 12 weeks in trough (morning pre-dose and pre-rescue bronchodilator) forced expiratory volume in 1 second (FEV1). Blood samples were collected from a patient subset to evaluate pharmacokinetics. Adverse events were monitored. RESULTS: Fp MDPI 25, 50, and 100 µg significantly improved change from baseline in trough FEV1 over 12 weeks compared with placebo (p < 0.01). There were no substantial differences in FEV1 change from baseline over 12 weeks between any Fp MDPI dose and Fp DPI 100 µg. Maximum observed concentration (Cmax) of Fp increased with increasing Fp MDPI doses; time of Cmax was similar across doses and treatments. Systemic exposures for Fp MDPI 25 and 50 µg were lower than that for Fp DPI 100 µg. The safety profile of Fp MDPI was consistent with that of Fp DPI. CONCLUSIONS: In this study, Fp MDPI 25 and 50 µg provided comparable efficacy and safety to Fp DPI 100 µg, with lower systemic exposure.

Safety, efficacy, and dose response of fluticasone propionate delivered via the novel MDPI in patients with severe asthma: A randomized, controlled, dose-ranging study.

OBJECTIVE: Evaluate fluticasone propionate (Fp) using a novel, inhalation-driven, multidose dry powder inhaler (MDPI) in patients with severe persistent asthma, versus placebo MDPI and Fp dry powder inhaler (DPI). METHODS: Patients with persistent asthma despite use of high-dose inhaled corticosteroids were randomized to Fp MDPI 50, 100, 200, or 400 mcg; Fp DPI 250 mcg; or placebo MDPI twice daily for 12 weeks. The primary outcome measure was change from baseline in trough forced expiratory volume in 1 second (FEV1) over the 12-week period, compared with placebo; secondary measures included change from baseline in peak expiratory flow (PEF), rescue inhaler use, and time to withdrawal due to meeting stopping criteria. Safety included adverse events and laboratory evaluations. RESULTS: Six hundred forty patients were randomized; 459 (72%) completed the study. Numerical dose-related improvements in FEV1 were observed in all Fp MDPI groups over 12 weeks but were not significantly greater versus placebo. Increases in morning PEF (baseline to week 12) were substantially greater than placebo in all Fp MDPI groups. The Fp MDPI and Fp DPI groups had substantial reductions in rescue inhaler use from baseline to end point versus placebo (p ≤ 0.05). Efficacy was comparable between Fp MDPI and Fp DPI. No new safety signals were detected; the safety profile of Fp MDPI was similar to that of Fp DPI. CONCLUSIONS: Clinical benefit observed with Fp MDPI in patients with persistent asthma was comparable to Fp DPI. Safety was reassuring with no unexpected findings. These results support further evaluation of Fp MDPI in asthma. (ClinicalTrials.gov identifier NCT01576718; EudraCT number 2010-023601-35).

A Novel Strategy to Increase Identification of African-Born People With Chronic Hepatitis B Virus Infection in the Chicago Metropolitan Area, 2012-2014.

INTRODUCTION: Most research on hepatitis B virus (HBV) infection in the United States is limited to Asian populations, despite an equally high prevalence among African immigrants. The purpose of this study was to determine testing and detection rates of HBV infection among African-born people residing in the Chicago metropolitan area. METHODS: A hepatitis education and prevention program was developed in collaboration with academic, clinical, and community partners for immigrant and refugee populations at risk for HBV infection. Community health workers implemented chain referral sampling, a novel strategy for recruiting hard-to-reach participants, targeting African-born participants. Participants were tested in both clinical and nonclinical settings. To assess infection status, blood samples were obtained for hepatitis B surface antigen (HBsAg), core antibody, and surface antibody testing. Demographic information was collected on age, sex, health insurance status, country of origin, and years residing in the United States. Participants were notified of testing results, and HBsAg-positive participants were referred for follow-up medical care. RESULTS: Of 1,000 African-born people who received education, 445 (45%) agreed to participate in HBV screening. There were 386 (87%) participants tested in clinical and 59 (13%) tested in nonclinical sites. Compared with participants who were tested in clinical settings, participants tested in nonclinical settings were older, were less likely to have health insurance, and had lived in the United States longer (P < .005 for each). Of these, most were from the Democratic Republic of the Congo (14%), Nigeria (13%), Ghana (11%), Somalia (11%), or Ethiopia (10%). There were 35 (8%) HBsAg-positive people, 37% had evidence of past infection, and 29% were immune. CONCLUSIONS: Chain referral sampling identified many at-risk African-born people with chronic HBV infection. The large proportion of HBsAg-positive people in this sample reinforces the need for health promotion programs that are culturally appropriate and community-driven.

Size misperception among overweight and obese families.

BACKGROUND: Perception of body size is a key factor driving health behavior. Mothers directly influence children's nutritional and exercise behaviors. Mothers of ethnic minority groups and lower socioeconomic status are less likely to correctly identify young children as overweight or obese. Little evaluation has been done of the inverse--the child's perception of the mother's weight. OBJECTIVE: To determine awareness of weight status among mother-child dyads (n = 506). DESIGN: Cross-sectional study conducted in an outpatient pediatric dental clinic of Columbia University Medical Center, New York, NY. PARTICIPANTS: Primarily Hispanic (82.2 %) mothers (n = 253), 38.8 ± 7.5 years of age, and children (n = 253), 10.5 ± 1.4 years of age, responding to a questionnaire adapted from the validated Behavioral Risk Factor Surveillance System. MAIN MEASURES: Anthropometric measures-including height, weight, and waist circumference-and awareness of self-size and size of other generation were obtained. KEY RESULTS: 71.4 % of obese adults and 35.1 % of overweight adults underestimated size, vs. 8.6 % of normal-weight (NW) adults (both p < 0.001). Among overweight and obese children, 86.3 % and 62.3 % underestimated their size, vs. 14.9 % NW children (both p < 0.001). Among mothers with overweight children, 80.0 % underestimated their child's weight, vs. 7.1 % of mothers with NW children (p < 0.001); 23.1 % of mothers with obese children also underestimated their child's weight (p < 0.01). Among children with obese mothers, only 13.0 % correctly classified the adult's size, vs. 76.5 % with NW mothers (p < 0.001). Among obese mothers, 20.8 % classified overweight body size as ideal, vs. 1.2 % among NW mothers (p < 0.001). CONCLUSION: Overweight/obese adults and children frequently underestimate their size. Adults misjudge overweight/obese children as being of normal weight, and children of obese mothers often underestimate the adult's size. Failure to recognize overweight/obesity status among adults and children can lead to prolonged exposure to obesity-related comorbidities.

Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel, dry powder inhaler versus a prevailing dry powder inhaler and a metered-dose inhaler.

BACKGROUND: A novel inhalation-driven multidose dry powder inhaler (MDPI) that eliminates the need for the patient to coordinate device actuation with inhalation has been developed for delivery of inhaled asthma medications. OBJECTIVE: To characterize the pharmacokinetics of single-dose fluticasone propionate (Fp) MDPI compared with single doses of Fp dry powder inhaler (DPI) and a metered-dose inhaler (MDI) in healthy subjects. METHODS: This was a single-center, open-label, randomized, three-period crossover, single-dose pilot study in healthy adults ages 18 to 45 years. Eligible subjects (N = 18) were randomized to one of six treatment sequences that contained three treatment arms: Fp MDPI 400 µg/inhalation × two inhalations (800 µg total dose); Fp DPI 250 µg/inhalation × four (1000 µg total dose); and Fp MDI 220 µg/inhalation × four (880 µg total dose). Pharmacokinetics (area under concentration-versus-time curve [AUC], maximum plasma concentration [Cmax], time to Cmax [tmax], and elimination half-life [t½]), safety, and tolerability were assessed for each treatment. RESULTS: Plasma Fp concentration-versus-time curves were comparable across treatments. Geometric mean AUC0-t and Cmax for Fp MDPI 800 µg were 19% and 18% higher, respectively, compared with Fp DPI 1000 µg, and 47% and 82% higher, respectively, compared with Fp MDI 880 µg. Median tmax (60.0-60.6 minutes) and median t1/2 (9.1-9.8 hours) were comparable across the three treatments. Single-dose Fp was well tolerated, with no new safety issues noted. CONCLUSION: Single-dose administration of Fp MDPI 800 µg produced systemic exposure comparable with those for Fp DPI 1000 µg and Fp MDI 880 µg.

Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children.

Investigation of 31 of Roma patients with congenital lactic acidosis (CLA) from Bulgaria identified homozygosity for the R446* mutation in the PDHX gene as the most common cause of the disorder in this ethnic group. It accounted for around 60% of patients in the study and over 25% of all CLA cases referred to the National Genetic Laboratory in Bulgaria. The detection of a homozygous patient from Hungary and carriers among population controls from Romania and Slovakia suggests a wide spread of the mutation in the European Roma population. The clinical phenotype of the twenty R446* homozygotes was relatively homogeneous, with lactic acidosis crisis in the first days or months of life as the most common initial presentation (15/20 patients) and delayed psychomotor development and/or seizures in infancy as the leading manifestations in a smaller group (5/20 patients). The subsequent clinical picture was dominated by impaired physical growth and a very consistent pattern of static cerebral palsy-like encephalopathy with spasticity and severe to profound mental retardation seen in over 80% of cases. Most patients had a positive family history. We propose testing for the R446* mutation in PDHX as a rapid first screening in Roma infants with metabolic acidosis. It will facilitate and accelerate diagnosis in a large proportion of cases, allow early rehabilitation to alleviate the chronic clinical course, and prevent further affected births in high-risk families.

Transitioning From Trainee to Practicing Pathologist: A Prospective Multi-institutional Survey of the Challenges Early Career Anatomic Pathologists Encounter When Entering Independent Practice.

CONTEXT.­: Pathology training programs generally prepare graduates well for the workforce, but there may be other aspects to navigating a job that make the transition from being a trainee to a practicing pathologist challenging. OBJECTIVE.­: To identify perceived challenges of independent practice for early career pathologists and assess how these impressions evolve throughout their first year. DESIGN.­: A survey was distributed to 12 anatomic pathology fellows from 4 institutions near the end of their final training year, and 6 months and 1 year after starting their first job. The surveys queried participants' comfort level with signing out cases independently and interacting with colleagues/trainees via Likert attitude scale questions with free-text segments to elaborate on challenges experienced. RESULTS.­: The response rate to all 3 surveys was 100%. Confidence and comfort level with different aspects of independent sign-out increased incrementally over time. Main challenges encountered at 6 months included a high case load, signing out cases in areas outside of their subspecialty, time management, balancing teaching while signing out, laboratory issues, and developing relationships with clinicians. At 12 months, main challenges included time management, high case load, understaffing, laboratory issues, and signing out cases in areas outside of their subspecialty. CONCLUSIONS.­: This study identified real-time challenges faced by those adjusting to their first year of independent practice. By gaining a better understanding of the factors that make this transition challenging, we can find tailored ways to support our early career pathologists.

Targeted RNA Sequencing Highlights a Diverse Genomic and Morphologic Landscape in Low-grade Endometrial Stromal Sarcoma, Including Novel Fusion Genes.

Low-grade endometrial stromal sarcoma (LGESS) represents a morphologically and genetically heterogenous mesenchymal neoplasm. Previous work has shown that approximately half of LGESS are characterized by JAZF1::SUZ12 gene fusions, while a smaller proportion involves rearrangement of other genes. However, a subset of cases has no known genetic abnormalities. To better characterize the genomic landscape of LGESS, we interrogated a cohort with targeted RNA sequencing (RNA-Seq). Cases previously diagnosed as low-grade endometrial stromal neoplasia (n=51) were identified and re-reviewed for morphology and subjected to RNA-Seq, of which 47 were successfully sequenced. The median patient age was 49 years (range: 19 to 85). The most commonly detected fusions were JAZF1::SUZ12 (n=26, 55%) and BRD8::PHF1 (n=3, 6%). In addition to the usual/typical LGESS morphology, some JAZF1::SUZ12 fusion tumors showed other morphologies, including fibrous, smooth muscle, sex-cord differentiation, and myxoid change. Novel translocations were identified in 2 cases: MEAF6::PTGR2 and HCFC1::PHF1 . Ten tumors (21%) had no identifiable fusion, despite a similar morphology and immunophenotype to fusion-positive cases. This suggests that a subset of cases may be attributable to fusion products among genes that are not covered by the assay, or perhaps altogether different molecular mechanisms. In all, these findings confirm that RNA-Seq is a potentially useful ancillary test in the diagnosis of endometrial stromal neoplasms and highlight their diverse morphology.

Prevention of Orthopaedic Implant Infection in Patients Undergoing Dental Procedures.

The Prevention of Orthopaedic Implant Infection in Patients Undergoing Dental Procedures evidence-based clinical practice guideline was codeveloped by the American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association. This guideline replaces the previous AAOS Information Statement, "Antibiotic Prophylaxis in Bacteremia in Patients With Joint Replacement," published in 2009. Based on the best current evidence and a systematic review of published studies, three recommendations have been created to guide clinical practice in the prevention of orthopaedic implant infections in patients undergoing dental procedures. The first recommendation is graded as Limited; this recommendation proposes that the practitioner consider changing the long-standing practice of routinely prescribing prophylactic antibiotic for patients with orthopaedic implants who undergo dental procedures. The second, graded as Inconclusive, addresses the use of oral topical antimicrobials in the prevention of periprosthetic joint infections. The third recommendation, a Consensus statement, addresses the maintenance of good oral hygiene.

Cytology of Benign Peritoneal Fluids and Pelvic Washing Specimens: Diagnostic Cytomorphologic Features and Pitfalls.

BACKGROUND: Pelvic washing and peritoneal fluid cytology specimens are used to detect peritoneal spread of malignancies. In most cases, identification of malignancy in these specimens is straightforward, but benign processes may occasionally mimic neoplasia and cause diagnostic difficulty. SUMMARY: In this article, we perform a focused review of common benign entities encountered in pelvic washing and peritoneal fluid specimens during routine practice which may cause difficulty and discuss helpful features for avoiding diagnostic pitfalls. KEY MESSAGES: Application of strict cytomorphologic criteria, along with judicious use of ancillary studies and correlation with clinical, intraoperative, radiologic, and other pathologic findings, can help resolve most problematic cases.

Home-based aerobic conditioning for management of symptoms of fibromyalgia: a pilot study.

OBJECTIVE: This pilot study was designed to evaluate the impact of a home-based aerobic conditioning program on symptoms of fibromyalgia and determine if changes in symptoms were related to quantitative changes in aerobic conditioning (VO(2) max). METHODS: Twenty-six sedentary individuals diagnosed with fibromyalgia syndrome participated in an individualized 12-week home-based aerobic exercise program with the goal of daily aerobic exercise of 30 minutes at 80% of estimated maximum heart rate. The aerobic conditioning took place in the participants' homes, outdoors, or at local fitness clubs at the discretion of the individual under the supervision of a physical therapist. Patients were evaluated at baseline and completion for physiological level of aerobic conditioning (VO(2) max), pain ratings, pain disability, depression, and stress. RESULTS: In this pilot study subjects who successfully completed the 12-week exercise program demonstrated an increase in aerobic conditioning, a trend toward decrease in pain measured by the McGill Pain Questionnaire-Short Form and a weak trend toward improvements in visual analog scale, depression, and perceived stress. Patients who were unable or unwilling to complete this aerobic conditioning program reported significantly greater pain and perceived disability (and a trend toward more depression) at baseline than those who completed the program. CONCLUSIONS: Patients suffering from fibromyalgia who can participate in an aerobic conditioning program may experience physiological and psychological benefits, perhaps with improvement in symptoms of fibromyalgia, specifically pain ratings. More definitive trials are needed, and this pilot demonstrates the feasibility of the quantitative VO2 max method. Subjects who experience significant perceived disability and negative affective symptoms are not likely to maintain a home-based conditioning program, and may need a more comprehensive interdisciplinary program offering greater psychological and social support.

NTRK -Rearranged Uterine Sarcomas: Clinicopathologic Features of 15 Cases, Literature Review, and Risk Stratification.

NTRK -rearranged uterine sarcomas are rare spindle cell neoplasms that typically arise in the uterine cervix of young women. Some tumors recur or metastasize, but features which predict behavior have not been identified to date. Distinguishing these tumors from morphologic mimics is significant because patients with advanced stage disease may be treated with TRK inhibitors. Herein, we present 15 cases of NTRK- rearranged uterine sarcomas, the largest series to date. Median patient age was 35 years (range: 16 to 61). The majority arose in the uterine cervix (n=14) and all but 2 were organ-confined at diagnosis. Tumors were composed of an infiltrative, fascicular proliferation of spindle cells and most showed mild-to-moderate cytologic atypia. All were pan-TRK positive by immunohistochemistry (13/13); S100 (11/13) and CD34 (6/10) were usually positive. RNA or DNA sequencing found NTRK1 (10/13) and NTRK3 (3/13) fusions with partners TPR , TPM3 , EML4 , TFG , SPECC1L , C16orf72 , and IRF2BP2 . Unusual morphology was seen in 2 tumors which were originally diagnosed as unclassifiable uterine sarcomas, 1 of which also harbored TP53 mutations. Follow up was available for 9 patients, of whom 3 died of disease. By incorporating outcome data of previously reported tumors, adverse prognostic features were identified, including a mitotic index ≥8 per 10 high-power fields, lymphovascular invasion, necrosis, and NTRK3 fusion. Patients with tumors which lacked any of these 4 features had an excellent prognosis. This study expands the morphologic spectrum of NTRK -rearranged uterine sarcomas and identifies features which can be used for risk stratification.