bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological and Clinical Characteristics of Melioidosis Caused by Gentamicin-SusceptibleBurkholderia pseudomalleiin Sarawak, Malaysia
Authors: Sia Tonnii L L , Mohan Anand , Ooi Mong-How , Chien Su-Lin , Tan Lee-See , Goh Charles , Pang Daniel C L , Currie Bart J , Wong Jin-Shyan , Podin Yuwana
Published: September 2021

Background

Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to a broad range of antibiotics, including aminoglycosides. In Sarawak, Malaysia, a high proportion of melioidosis cases are caused by gentamicin-susceptible isolates. There are limited epidemiological and clinical data on these infections.

Methods

We conducted a retrospective study of culture-confirmed melioidosis among adults admitted to Bintulu Hospital in Sarawak, Malaysia, from January 2011 until December 2016.

Results

One hundred forty-eight adults with culture-confirmed melioidosis were identified. Of 129 (87%) tested, 84 (65%) had gentamicin-susceptible B pseudomallei. The average annual incidence of melioidosis was 12.3 per 100 000 population, with marked variation between districts ranging from 5.8 to 29.3 per 100 000 population. Rural districts had higher incidences of melioidosis and overwhelmingly larger proportions of gentamicin-susceptible B pseudomallei infection. Significantly more patients with gentamicin-susceptible infection had no identified risk factors, with diabetes less frequently present in this group. Ninety-eight percent had acute presentations. Pneumonia, reported in 71%, was the most common presentation. Splenic abscesses were found in 54% of those imaged. Bacteremia was present in 88%; septic shock occurred in 47%. Forty-five (35%) patients died. No differences in clinical, laboratory, or outcome characteristics were noted between gentamicin-susceptible and gentamicin-resistant infections.

Conclusions

Gentamicin-susceptible B pseudomallei infections are common in Sarawak and dominate in the high-incidence rural interior regions. Clinical manifestations and outcomes are the same as for gentamicin-resistant B pseudomallei infections. Further studies are required to determine if all gentamicin-susceptible B pseudomallei infections in Sarawak are clonal and to ascertain their environmental drivers and niches.
Spatial distribution of the X-ray-emitting plasma of SS Cygni in quiescence and outburst
Authors: Takeo Mai , Hayashi Takayuki , Ishida Manabu , Nakaniwa Nozomi , Maeda Yoshitomo
Published: September 2021

We present our analysis of the Suzaku data of SS Cygni (SS Cyg) from 2005 both in quiescence and outburst. A fluorescent iron Kα line bears significant information about the geometry of an X-ray-emitting hot plasma and a cold reflector, such as the surfaces of the white dwarf (WD) and the accretion disk (AD). Our reflection simulation has revealed that the X-ray-emitting hot plasma is located either very close to the WD surface in the boundary layer (BL), with an upper limit radial position of <1.004 times the white dwarf radius (RWD), or near the entrance of the BL where the optically thick AD is truncated at a distance of 1.14–1.27 RWD for the assumed WD mass of 1.19 M⊙ in quiescence. In the latter configuration, the plasma torus is located just above the inner edge of the AD. The result suggests that the accreting matter is heated up close to the maximum temperature immediately after the matter enters the BL. The matter probably expands precipitously at the entrance of the BL and leaves the disk plane to reach a height comparable to the radial distance of the plasma torus from the center of the WD. In outburst, on the other hand, our spectral analysis favors the picture that the optically thick disk reaches the WD surface. In addition, the plasma distributes above the disk like coronae, as suggested by a previous study, and the 90% upper limit of the coronae radial position is 1.2 RWD.
Changes in the International Classification of Functioning, Disability, and Health Components “Activity/Participation” as Predicted Through Patient-Reported Outcomes Along With Comprehensive Back Pain Rehabilitation
Authors: Kienbacher Thomas , Fehrmann Elisabeth , Tuechler Kerstin , Habenicht Richard , Mair Patrick , Friedl Anna , Oeffel Christian , Ebenbichler Gerold
Published: September 2021

Objectives:

The World Health Organization (WHO) recommended the International Classification of Functioning, Disability and Health (ICF) but its use in clinical practice is sparse. This study investigated the limitations and restrictions in the most relevant brief ICF core set categories for chronic low back pain (cLBP) as automatically predicted from routinely measured outcomes using a novel, validated mapping algorithm.

Materials and Methods:

Of 2718 cLBP patients recruited, data from 1541 (64% females) were available from before and at the end of 6 months comprehensive outpatient rehabilitation. Assessments included the Roland Morris Disability Questionnaire (RMDQ) and Pain Disability Index (PDI) questionnaires, the percentage of patients with predicted limitations and restrictions in important activity and participation ICF categories, bodily functional measurements, pain intensity, and anxiety/depression (EQ-5D).

Results:

At baseline, both the RMDQ and the PDI measures were within the third of the lowest disability scores whilst 80% of the patients had limitations with “maintaining a body position” and 30% with “walking” ICF categories. Intervention-associated gains in the maximum isometric lumbar extension and flexion strength and the lumbar range of motion were significant overall, but improvements in patients’ ICF limitations/restrictions varied. Anxiety/depression, lumbar range of motion, and extension strength all had a significant impact on the majority of the ICF categories, whereas flexion strength had none.

Discussion:

The rate of patients with predicted limitations/restrictions in activity/participation ICF core categories for cLBP partly mirrored disability levels and the impact of the body function scores on these limitations/restrictions in ICF categories was varied. Thus, assessing problems in the ICF activity/participation core categories is of relevance to clinical practice for both treatment goal setting and intervention planning. This may be achieved by computer-generated mapping without additional time burden.
Calculated Plasma Volume Status Is Associated With Mortality in Acute Respiratory Distress Syndrome
Authors: Niedermeyer Shannon E. , Stephens R. Scott , Kim Bo Soo , Metkus Thomas S.
Published: September 2021

OBJECTIVES:

The optimal method to assess fluid overload in acute respiratory distress syndrome is not known, and current techniques have limitations. Plasma volume status has emerged as a noninvasive method to assess volume status and is defined as the percentage alteration from ideal plasma volume. We hypothesized that plasma volume status would suggest the presence of significant excess volume and therefore correlate with mortality in acute respiratory distress syndrome.

DESIGN AND SETTING:

This is a retrospective cohort study of subjects enrolled in four previously completed National Heart Lung and Blood Institute-sponsored acute respiratory distress syndrome trials, using data from the National Institutes of Health Biologic Specimen and Data Repository Information Coordinating Center repository.

PATIENTS:

Study subjects included 3,165 patients with acute respiratory distress syndrome previously enrolled in National Heart Lung and Blood Institute-sponsored acute respiratory distress syndrome trials.

MEASUREMENTS AND MAIN RESULTS:

The exposure variable of interest was plasma volume status, calculated as the percentage alteration of actual plasma volume calculated on the basis of weight and hematocrit using sex-specific constants. We performed Kaplan-Meier survival analysis and univariable and adjusted Cox proportional hazard models to determine the association of plasma volume status with 60-day mortality. The median age of subjects was 52 years (interquartile range, 40–63 yr). Median plasma volume status was 5.9% (interquartile range, –2.4% to 13.6%), and overall, 68% of subjects had positive plasma volume status suggesting plasma volume higher than ideal plasma volume. In adjusted models, plasma volume status greater than median was associated with 38% greater risk for mortality (hazard ratio, 1.38; 95% CI, 1.20–1.59; p < 0.001). Each interquartile range increase in plasma volume status was associated with greater mortality in adjusted models (hazard ratio, 1.24 per interquartile range increase; 95% CI, 1.13–1.36; p < 0.001). Plasma volume status greater than median was associated with fewer ventilator-free days (18 vs 19 d; p = 0.0026) and ICU-free days (15 vs 17 d; p = 0.0001).

CONCLUSIONS:

Plasma volume status is independently associated with mortality, ICU-free days, and ventilator-free days among subjects with acute respiratory distress syndrome. Plasma volume status could be considered for risk-stratification and to direct therapy, particularly fluid management.
The road to chemotherapy-free treatment in chronic lymphocytic leukaemia
Authors: Albiol Nil , Arguello-Tomas Miguel , Moreno Carol
Published: September 2021

Purpose of review

The treatment landscape of chronic lymphocytic leukaemia (CLL) has tremendously evolved in the last decades, from chemo to chemoimmunotherapy (CIT) and, eventually, to pathway inhibitors that target critical pathways for leukaemic cells survival. Also, treatment goals are moving towards achieving undetectable minimal residual disease with little toxicity.

Recent findings

We performed a thorough review of the history of treatment approvals by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This review especially focuses on therapies that are currently approved by both agencies. The indications and particular characteristics of each drug are examined.

Currently available treatment approaches for CLL offer the opportunity to individualize therapy for every single patient with CLL. Inhibitors of B-cell receptor (BCR) signalling pathways and antiapoptotic proteins are nowadays the treatment of choice for most CLL patients, but CIT can be an option for younger and fit patients with low-risk disease [mutated IGHV, no del(11q) or del(17p)/TP53 mutations].
Fluid intake and blood pressure in children: the Salus per Aquam project
Authors: Ardissino Gianluigi , Perrone Michela , Ghiglia Silvia , Salice Patrizia , Tel Francesca , Dardi Elena , Bollani Tiziana , Mezzopane Antonella , Capone Valentina , Ardissino Maddalena , Vergori Antonio , Piantanida Sandra , Di Michele Silvia , Tchana Bertrand , Filippucci Lucia , De Luca Francesco , Consonni Dario , Buzzetti Roberto
Published: September 2021

Background:

Sodium intake is known to contribute to the development of hypertension, thus intake reduction is a cornerstone in the prevention and management of hypertension. The increase in renal sodium excretion might represent a further potential preventive and/or therapeutic opportunity.

Objective:

To explore the working hypothesis that an increased fluid intake can improve renal sodium handling towards a decrease in blood pressure.

Methods:

The SPA Project is a multicenter, observational, cross-sectional, cohort study investigating healthy children, aged 5–8 years as to sodium and fluid intake by means of urinary sodium and creatinine from multiple samples taken in different days in order to characterize them in lower/higher sodium and lower/higher fluid intake. Both SBP and DBP (by multiple office blood pressure measurements) were used as outcome measures.

Results:

Three hundred and thirty-nine healthy, nonoverweight children (51.6% boys) with a median age of 5.7 years old (IQR: 5.3–6.2) participated in the study but only 223 could be analyzed. Among children with higher sodium intake, those introducing more fluids, showed a significantly lower blood pressure (both systolic and diastolic) compared with those with lower fluid intake: systolic 86.0 ± 8.5 vs. 90.0 ± 8.1 mmHg; P = 0.014 and diastolic: 53.8 ± 4.9 vs. 58.6 ± 6.6 mmHg; P < 0.0001.

Conclusion:

An increased fluid intake is associated with a reduced blood pressure possibly by increasing renal sodium excretion. We speculate that this simple, highly acceptable, inexpensive, and harmless measure might have a role in preventing and/or minimizing the epidemics of hypertension and of its related morbidities both in children and in adults.
The interaction of hypertension and homocysteine increases the risk of mortality among middle-aged and older population in the United States
Authors: Zhao Wenyan , Gao Faliang , Lv Laidi , Chen Xi
Published: September 2021

Objectives:

To investigate the interaction of hypertension and total plasma homocysteine (tHcy) levels on risk of all-cause and cardiovascular disease (CVD) mortality among middle-aged and older population.

Methods:

This observational cohort study analyzed data from the National Health and Nutrition Examination Survey database (1999–2002 survey cycle). A generalized additive model (GAM) based on Cox proportional hazards models was applied to estimate the relationship of tHcy level with all-cause and CVD mortality. Stratification analyses by sex and renal function were performed.

Results:

Among 5724 individuals aged 40–85, 704 (12.3%) died, with 339 CVD deaths after a median follow-up period of 5.58 years. Mean age was 60.7 ± 13.4 years (49.6% men). In the fully adjusted model, we found that per 1 μmol/l increment of plasma tHcy was associated with 8% increased risk of all-cause mortality and 7% increased risk of CVD mortality in hypertensive participants. The adjusted hazard ratio (95% CIs) for all-cause and CVD mortality were 1.08 (1.06–1.10) and 1.07 (1.04–1.10), respectively. There were pronounced interactive effects between hypertension and tHcy levels on risk of all-cause mortality (P for interaction = 0.031).

Conclusion:

Hypertension and tHcy levels can interactively affect the risk of all-cause mortality among middle-aged and older population. Conceivably, hypertension may further enhance the ability of elevated tHcy to provoke the risk of all-cause mortality.
Peak exercise SBP and future risk of cardiovascular disease and mortality
Authors: Hedman Kristofer , Lindow Thomas , Cauwenberghs Nicholas , Carlén Anna , Elmberg Viktor , Brudin Lars , Ekström Magnus
Published: September 2021

Objectives:

This study aimed to evaluate the risk of all-cause mortality and incident cardiovascular disease associated with peak systolic blood pressure (PeakSBP) at clinical exercise testing.

Methods:

Data from 10 096 clinical exercise tests (54% men, age 18—85 years) was cross-linked with outcome data from national registries. PeakSBP was compared with recently published reference percentiles as well as expressed as percentage predicted PeakSBP using reference equations.

Natural cubic spline modelling and Cox regression were used to analyse data stratified by sex and baseline cardiovascular risk profile.

Results:

Median [IQR] follow-up times were 7.9 [5.7] years (all-cause mortality) and 5.6 [5.9] years (incident cardiovascular disease), respectively. The adjusted risk of all-cause mortality [hazard ratio, 95% confidence interval (95% CI)] for individuals with PeakSBP below the 10th percentile was 2.00 (1.59–2.52) in men and 2.60 (1.97–3.44) in women, compared with individuals within the 10th--90th percentile. The corresponding risk for incident cardiovascular disease was 1.55 (1.28–1.89, men) and 1.34 (1.05–1.71, women). For males in the upper 90th percentile, compared with individuals within the 10th--90th percentile, the adjusted risks of all-cause death and incident cardiovascular disease were 0.35 (0.22–0.54) and 0.72 (0.57–0.92), respectively, while not statistically significant in women. Spline modelling revealed a continuous increase in risk with PeakSBP values less than 100% of predicted in both sexes, with no increase in risk more than 100% of predicted.

Conclusion:

Low, but not high, PeakSBP was associated with an increased risk of mortality and future cardiovascular disease. Using reference standards for PeakSBP could facilitate clinical risk stratification across patients of varying sex, age and exercise capacity.
Circulating miR-3656 induces human umbilical vein endothelial cell injury by targeting eNOS and ADAMTS13: a novel biomarker for hypertension
Authors: Shi Jikang , Ren Yaxuan , Liu Sainan , Zhao Qian , Kong Fei , Guo Yanbo , Xu Jiayi , Liu Siyu , Qiao Yichun , Li Yong , Liu Yunkai , Liu Yawen , Cheng Yi
Published: September 2021

Background:

Hypertension, as one of the most common chronic diseases, is a major public health issue. Previous studies have shown that there are miRNAs differentially expressed in hypertensive patients. In addition, hypertension is closely related to endothelial dysfunction, and miRNAs have been identified as important molecular mediators for endothelial function. Therefore, it is necessary to identify specific miRNAs related to hypertension and explore their molecular mechanism in the progression of hypertension.

Methods:

We investigated the association of circulating levels of miR-3656 with hypertension. Furthermore, in-vitro studies were performed to investigate its possible mechanisms for hypertension in that the direct target genes of miR-3656 were confirmed using dual-luciferase reporter assay; moreover, the effects of miR-3656 on proliferation, migration, apoptosis, and microvascular rarefaction of HUVECs were investigated using MTS kit, wound-healing assay, FITC Annexin V apoptosis detection kit, and tube formation assay, correspondingly.

Results:

Circulating miR-3656 was upregulated in patients with hypertension. MiR-3656 suppressed the proliferation, migration, and angiogenesis of HUVECs, but promoted the apoptosis of HUVECs. In addition, eNOS and ADAMTS13 were direct target genes of miR-3656, and overexpression of eNOS and ADAMTS13 abolished the effect of miR-3656 on HUVECs.

Conclusion:

MiR-3656 is a potential biomarker for hypertension. MiR-3656 is involved in endothelial cellular injury implicated in hypertension by targeting eNOS and ADAMTS13.
Impact of COVID-19 on Patients Supported with a Left Ventricular Assist Device
Authors: Zakrzewski Jack , Coyle Laura , Aicher Tracy , Chickerillo Krystina , Gallagher Colleen , Kuper Katelyn , Sciamanna Chris , Chau Vinh Q. , Tatooles Antone
Published: September 2021

Patients on left ventricular assist device (LVAD) support may be susceptible to severe disease and complications from coronavirus disease-19 (COVID-19). The purpose of this study was to describe the clinical course of COVID-19 in LVAD patients. A retrospective review was performed at our center; 28 LVAD patients who developed COVID-19 between March 2020 and March 2021, and six patients with a prior COVID-19 infection who underwent LVAD implantation, were identified and examined. Of the 28 patients, nine (32%) died during the study period, five (18%) during their index hospitalization for COVID-19. Two patients (7%) presented with suspected pump thrombosis. In a nonadjusted binary regression logistic analysis, admission to the intensive care unit (unadjusted odds ratio, 7.6 [CI, 1.2–48], P = 0.03), and the need for mechanical ventilation (unadjusted odds ratio 14 [CI, 1.3–159], P = 0.03) were associated with mortality. The six patients who previously had COVID-19 and subsequently received a LVAD were on intra-aortic balloon pump and inotropic support at time of surgery. All six experienced a complicated and prolonged postoperative course. Three patients (50%) suffered from ischemic stroke, and there was one (17%) 30 day mortality. We observed an increased risk of morbidity and mortality in LVAD patients with COVID-19.
Nodal Merkel Cell Carcinoma With Neuroblastoma Differentiation: A Case Report and Review of the Literature
Authors: Mahapatra Lily , Mansour Mena , Chatterjee Deyali , Fields Ryan C. , Maluf Horacio , Dehner Louis P.
Published: September 2021

We report a case of a neuroendocrine carcinoma of the inguinal lymph node without a known identified primary site, which demonstrated the morphologic and immunophenotypic features of a Merkel cell carcinoma with neuroblastic differentiation. The neoplasm had a predominant high-grade neuroendocrine component with small cell features and a contiguous area with lobular foci of neuroblastic rosettes and fibrillary neuropil. Merkel cell carcinoma can occasionally demonstrate aberrant differentiation to other epithelial and nonepithelial cell lines, and this case is only the fourth in the available literature with neuroblastic differentiation. It is necessary to exclude a primary site of origin, but a few cases of primary neuroendocrine tumor of the lymph node have been described, with the inguinal region as the most common site of occurrence.
Spindle Cell Sinonasal Rhabdomyosarcoma in a 73-Year-Old Man: A Case Report
Authors: Wessinger Bronson C. , Morse Justin , Lewis James S. , Shinn Justin R. , Chandra Rakesh
Published: September 2021

Introduction

Rhabdomyosarcoma (RMS) is a malignant soft tissue neoplasm differentiating into primitive mesenchymal cells with partial skeletal muscle differentiation. It is rare, especially in the sinonasal cavity. We review available literature on sinonasal RMS and present a case report involving spindle cell sinonasal RMS, one of the rarest subtypes.

Case Report

A 73-year-old man with months of right-sided epiphora and nasal obstruction had abnormal soft tissue and calcification in the right nasal cavity on computed tomography. Nasal endoscopy revealed a smooth, firm mass involving the inferior turbinate. The mass was removed en bloc via endoscopic partial medial maxillectomy and ethmoidectomy. Gross pathologic examination revealed a mottled red, tan, firm, bosselated, and glistening mass, with irregular fragments of soft tissue and bone. Histologic examination showed a variably myxoid and fibrous neoplasm with hyalinization. Tumor cells were spindled with moderate pleomorphism and low mitotic activity. Immunohistochemistry was extensively positive for desmin and myoD1 and focally positive for smooth muscle actin. A diagnosis of sinonasal RMS, grade 2, was made.

Discussion/Conclusion

This is the first reported case of spindle cell RMS originating from the inferior turbinate. Sinonasal RMS has the worst prognosis of all primary sites, especially with age older than 65 years, alveolar subtype, primary tumor greater than 5 cm, high stage/group, and distant metastases. While the risk stratification system accounts for surgical and pathologic factors, more research is needed to determine how this guides selection of resection and/or chemoradiation.
Heterotopic Ossification of the Mesentery: A Rare Postoperative Complication
Authors: Sura Gloria Hopkins , Jackson Nicole R. , Yodzis Shirley , Fox Sharon E.
Published: September 2021

Heterotopic ossification is a rare, reactive condition, sometimes classified as a “pseudotumor,” involving the formation of bone within the soft tissues (Int J Surg Case Rep 2014;5:476–479), This process can occur as an undesirable pathologic sequela of trauma and surgery (J Am Acad Orthop Surg 2004;12:116–125). The few cases reported in the literature are almost exclusively in men with a predominance in people of African ancestry (J Am Acad Orthop Surg 2004;12:116–125; Bone Joint J 2016;98-B:761–766; Case Rep Surg 2019;2019:4036716). Reports of heterotopic ossification have been described in medical literature since 1692 as myositis ossificans progressiva (JBJS 1938;20:661–674). It was not until 1999 that the term “heterotopic mesenteric ossification” was formally used by Wilson et al to describe a complication found in post–abdominal surgical patients (Am J Surg Pathol 1999;23:1464–1470). Although the exact pathologic mechanism of heterotopic mesenteric ossification has not been elucidated, some hypotheses include differentiation of mesenchymal progenitor cells toward an osteogenic lineage, as well as proliferation of dislocated fragments of bone from other regions of the body (J Gastrointest Surg 2015;19:579–580). Since the late 1900s, fewer than 40 cases of mesenteric ossification have been reported. Limited gross and histologic description is available for pathologists and surgeons to identify this phenomenon; however, further data can be acquired at autopsy. Awareness of this condition on the part of clinicians, and early review and recognition by pathologists, may alter surgical management decisions and improve upon morbidity and mortality in these patients. We present gross and histologic examination of an advanced case of heterotopic ossification at autopsy, with a review of current management recommendations.
Urinary Bladder Inflammatory Myofibroblastic Tumor With Mutated TP53 and PPFIBP1-ALK Gene Fusion
Authors: Barbieri Andreia N. , Tallman Christopher T. , Satkunasivam Raj , Annunziata Joseph , Thomas Jessica S. , Olsen Randall J. , Shen Steven S. , Thrall Michael J. , Schwartz Mary R.
Published: September 2021

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm with distinct histologic features. Approximately 50% of these tumors harbor ALK gene rearrangements with multiple gene fusion partners described, a few of which are predictive of poor prognosis. One example is the ALK-RANBP2 gene rearrangement identified in cases of epithelioid myofibroblastic sarcomas. Many studies have attempted to identify other immunohistochemical or molecular features, which may be predictive of outcome, with conflicting results, particularly regarding the expression of p53. In addition, aberrant p53 expression may be used to favor a diagnosis of leiomyosarcoma over IMT. We present the case of a deeply invasive urinary bladder IMT with aberrant p53 expression and corresponding TP53 genomic alteration, the latter previously reported in only 2 unrelated cases of malignancy. Our case highlights that p53 aberrant expression and TP53 genomic alterations may be found in IMTs and may be related to IMT pathogenesis and prognosis. Furthermore, relying on absence of aberrant p53 expression in IMT in order to distinguish it from histologic mimickers may lead to potential diagnostic pitfalls. In addition, our case demonstrated weak immunohistochemical staining for ALK and was found to harbor a PPFIBP1-ALK gene fusion, previously described in only 2 reports of IMTs of the lung, also with associated negative or weak immunohistochemical staining for ALK.
Education in Autopsy: More Than the Y-Shaped Incision: Entrusting Trainees for the Future
Authors: Humphrey William O. , Mount Sharon L.
Published: September 2021

Training in autopsy encompasses the acquisition of skills and knowledge beyond the Y-shaped incision. In addition to learning basic tissue examination and processing skills, the autopsy service provides education in teamwork, professionalism and leadership, communication, public health, research, and self-reflection. Regardless of future specialization or practice setting, education provided by the autopsy has the potential to influence both the professional and personal lives of the trainees. Despite widespread agreement that autopsy education improves patient care, challenges to building and maintaining a dynamic and educational autopsy service exist and include factors that are both intrinsic and extrinsic to the practice of autopsy itself. Challenges including adequate volume of cases, knowledge of the procedure and skill in obtaining consent for autopsies, inclusion of an autopsy experience in medical school curriculums, competition for resident time, lack of subspecialists such as pediatric/perinatal and cardiac pathologists, and political action to gain support from regulatory bodies are addressed. Finally, we explore the way forward in autopsy education. Solutions such as the standardization of the educational autopsy, valuing the quality of competence over quantity of cases, and benefits of the Office of Decedent Affairs are discussed. By rededicating ourselves to the education of trainees via experiences on the autopsy service, we empower them to harness the many opportunities offered by the postmortem examination and ensure autopsy's seat at the table in 21st-century medicine.
Multipolar Neuropathology: Survival Strategies for Professional Loneliness
Authors: Richard Hope T.
Published: September 2021

The field of neuropathology has a rich history with strong ties to the clinical fields of neurosurgery and neurology. Until the mid-20th century, neuropathology was an apprenticeship in these fields after which it became a subspecialty within the field of pathology. Neuropathology remains a small subspecialty, encompassing only 2% of the actively practicing pathologists in the United States, which lends to the professional loneliness that may occur with neuropathologists. This review offers a guide that covers the most important aspects of a neuropathology practice, including the use of telepathology in a neuropathology practice, the most important aspects of intraoperative evaluation of surgical neuropathology specimens, fellowship training, and the role of neuropathologists in forensic pathology.
The End
Authors: Wiles Austin B.
Published: September 2021

Arguments in defense of the medical autopsy tend to be grounded in quantitative ideas of utility. As such, these defenses limit their techniques and core concepts to the same principles that ground the practice of contemporary medicine. While this tactic seems reasonable, as arguments should always be cognizant of the context for which they are intended, the practice of medical autopsy continues to decline. The conceptual framework of the practice of medicine itself plays a role in the decline of the autopsy. It is difficult to imagine stopping or reversing the effacement of the medical autopsy without overcoming this framework. This review examines the genealogy of arguments about the importance of medical autopsy and develops some new conceptual tools to defend it. Three related notions are explored. Each of these goes beyond the customary, and often unexamined, types of argumentation in contemporary medicine. This review seeks to answer the question: What if the autopsy was gone? What would an autopsy of the practice of autopsy itself reveal?
Staging of Resected Lung Cancers
Authors: Burke Allen , Legesse Teklu
Published: September 2021

In this review, the authors discuss the current pathologic staging of lung cancers, with emphasis on pointers to filling out synoptic forms. A table that combines clinical staging (which oncologists and surgeons use to direct care) with pathologic underpinnings is provided so that a pathologist can easily translate pTNM stage with clinical stage. The major areas of difficulty in pathologic staging are addressed in separate sections, including margins, multiple nodules, determination of invasion, treatment effect, and invasion of adjacent structures.
Eosinophilic Myocarditis: Differential Diagnosis on Endomyocardial Biopsy
Authors: Jacobs Jonathan , Burke Allen
Published: September 2021

Eosinophilic myocarditis has multiple causes. When diagnosed on biopsy, sampling precludes diagnosing a specific cause in most cases. We report a case of presumed eosinophilic granulomatosis with polyangiitis diagnosed on endomyocardial biopsy and discuss the differential diagnosis.
Rhinoscleroma: A Rare Chronic Infectious Cause of Nasal Mass Lesions in the United States
Authors: Oentoro Jaymie E. , Allard Felicia D.
Published: September 2021

Rhinoscleroma is a chronic, progressive, granulomatous infection of the upper airways due to Klebsiella rhinoscleromatis. It is endemic to certain regions of Africa, Southeast Asia, Mexico, Central and South America, and Central and Eastern Europe but is rarely seen in the United States. We report the case of a 33-year-old man who presented with a 6-month history of progressive bilateral nasal obstruction that was unresponsive to medical therapy. The patient underwent surgical excision with histologic findings diagnostic of rhinoscleroma. Herein, we present this uncommon case, review the clinical and diagnostic features of rhinoscleroma, and discuss potential clinical and histologic mimics.
Low-Grade Biphenotypic Sinonasal Sarcoma: Case Report, Current Understanding, and Differential Diagnosis
Authors: Coppock Joseph D. , Stelow Edward B.
Published: September 2021

Low-grade biphenotypic sinonasal sarcoma (BSS) is a rare, locally aggressive mesenchymal neoplasm of the sinonasal tract defined by dual expression of neural and myogenic antigens and recurrent PAX3 (paired box gene 3) gene rearrangements. We herein present the case of a 53-year-old woman with an incidentally identified lesion on surveillance magnetic resonance imaging for a pituitary microadenoma, ultimately leading to biopsy and resection of a low-grade BSS. Because of its relatively indolent behavior and extensive differential diagnosis, recognition and appropriate diagnostic workup of this entity are of utmost importance. The current understanding of low-grade BSS, its diagnosis, and differential diagnosis in the sinonasal tract are discussed.
Sinonasal Ameloblastoma: A Case Report and a Review of Gnathic Lesions That Occur in the Sinonasal Tract
Authors: Whitehair Rachel M. , Stelow Edward B.
Published: September 2021

Primary sinonasal ameloblastomas are rare, benign odontogenic lesions that are locally aggressive. We report a case of a primary sinonasal ameloblastoma in a 65-year-old man who presented with sinonasal obstruction and rhinorrhea. The clinicopathologic features of this entity are discussed, along with the differential diagnosis and other gnathic lesions that present as sinonasal lesions.
Nasal Chondromesenchymal Hamartoma in a Patient With DICER1-Predisposition Syndrome
Authors: Zadeh Sara L. , Stelow Ed B.
Published: September 2021

Abstracts

Nasal chondromesenchymal hamartomas (CMHs) are extremely rare tumors that are sometimes seen in patients with germline DICER1 mutations. These patients are also at increased risk of pleuropulmonary blastomas, as well as other uncommon tumors. We present the case of an 8-year-old girl with a history of pleuropulmonary blastoma who presented with worsening nasal obstruction and clinical symptoms of sinusitis secondary to a nasal CMH. The diagnosis of nasal CMH is discussed, as well as DICER1 syndrome.
Considerations for Social Needs Screening in a Local Public Health Agency
Authors: Gordon Leslene E. , Nguyen Allison W. , Agrawal Kelli R.
Published: September 2021

Context:

The social determinants of health impact the health outcomes of local public health agency clients. This report shows how the Florida Department of Health in Hillsborough County (DOH) sought to address this for its clients.

Program:

This midstream intervention identified individual DOH client needs and navigated clients to community resources to address these social needs.

Implementation:

During the 2019 program, 768 DOH clients were screened, with 77% reporting having 1 or more social needs.

Evaluation:

Staff and clients identified various challenges clients faced navigating resources on their own, and the value in having resource navigators within the local public health agency.

Discussion:

Program findings demonstrated alignment with priorities in the Community Health Assessment, leading to engagement of specific partners and planning for population-level policy interventions. Social needs screenings present a unique opportunity for local public health agencies to improve the circumstances of clients and implement health equity approaches in their communities.
Add-on Oxytocin in the Treatment of Postpartum Acute Schizophrenia: A Case Report
Authors: Medved Sara , Bajs JanoviĆ Maja , Štimac Zoran , MihaljeviĆ-Peleš Alma
Published: September 2021

An increasing body of research has been published concerning the potential impact of oxytocin (OT) in the pathophysiology of neuropsychiatric disorders that affect social functioning, such as schizophrenia. The possible therapeutic effect of OT in promoting mother-child bonding could be valuable in the management of postpartum psychosis. Studies on the efficacy of OT as an add-on therapy in the treatment of schizophrenia have found reductions in both positive and negative symptoms. The patient in the case reported here developed her second psychotic episode at the age of 22, a month after delivering her first child. Four weeks after treatment with aripiprazole was initiated, the patient’s negative symptoms persisted, causing problems in the mother-child interaction. Intranasal OT (40 IU/d) was then added to the aripiprazole. Assessment scales [the Positive and Negative Syndrome Scale (PANSS), the Disability Assessment Schedule (WHODAS 2.0), and the Barkin Index of Maternal Functioning (BIMF)] and qualitative data from her caregiver were obtained at baseline and in the third and eighth weeks after the end of the OT therapy. Improvement was observed on almost all of the domains of the WHODAS 2.0 and the BIMF, as well as on the PANSS negative and general psychopathology scales. Data from the patient’s caregiver indicated an overall improvement in mother-child interaction. These results, especially the improvement in results on the PANSS scale, are similar to findings from previous studies in patients with schizophrenia. OT seems to boost the antipsychotic effect on positive symptoms through the OT dopamine pathway, while the effect on negative symptoms probably involves a more general mechanism. Because the postpartum period is of immense significance for child development and mental well-being, future research to investigate the therapeutic efficacy of OT in the management of postpartum psychosis is warranted.
Charting and Handling Therapeutic Drug Monitoring Results: How they Differ From Most Laboratory Results
Authors: Preskorn Sheldon H.
Published: September 2021

Therapeutic drug monitoring (TDM) results are a biological measure of the ability of the patient to clear a drug as long as the patient is adhering to the prescribed dosage. If the patient is not adherent, then TDM can provide evidence of such nonadherence. To properly interpret TDM results, several variables must be considered. First and foremost is the dose the patient is supposed to be taking. The second variable is whether the patient should have achieved a steady-state condition, which means that the amount of drug the patient is taking in a day is equal to the amount the patient is eliminating in the same day so that the level will not change unless changes occur in either the dosing rate or the ability of the patient to clear the drug. For drugs with a half-life of 24 hours, steady state typically occurs when the patient has been taking the same dose for 5 to 7 days (ie, 5 x the half-life). The third variable is the time between when the last dose was taken and the sample was obtained. Ideally, for most drugs, that desired interval is 10 to 12 hours after the last dose was taken assuming the patient is taking the dose daily as different rules apply for depot medications. There are 2 reasons for this stipulation. First, this interval will best reflect the average concentration that the patient achieves over the daily dosing interval on that drug. Second, for most orally administered drugs, the value that is obtained 10 to 12 hours after the last dose will not be influenced by differences in the absorption of the drug. In contrast, if the sample is obtained during the absorption phase, the plasma concentration can be both much higher and less predictable than is the case when absorption is complete. Therefore, these 3 variables must be included when recording TDM results in the chart. As explained in this column, the TDM result without this information is not optimally interpretable. Parenthetically, TDM results do not need to be repeated (unless specific concerns arise as explained in this column), because these results are a measure of the ability of the patient to clear the drug. For depot medications (eg, antipsychotics), the results should be obtained at the end of the dosing cycle just before the administration of the drug and after the patient has ideally received 4 to 5 injections at equal intervals (eg, monthly) to be near steady-state. Parenthetically, TDM at the appropriate fixed interval (usually monthly) with depot medications is much less sensitive to timing issues than TDM of orally administered drugs. This column explains the rationale for obtaining TDM results, principally focusing on orally administered drugs and how to optimally chart and disseminate these results.
Translabial Ultrasound for Assessment of Synthetic Midurethral Sling Complications
Authors: Wermuth Daniela Escobar , Sheridan Alison , Oliver Janine , Glanc Phyllis , Khatri Gaurav , Bagley Anjuli , Patel Nayana
Published: September 2021

Translabial ultrasound (TLUS) is an inexpensive, noninvasive imaging modality traditionally used for assessment of pelvic organ prolapse. The utility of TLUS has recently been expanded to the evaluation of synthetic midurethral slings (MUS) surgically implanted for management of stress urinary incontinence. The purpose of this article is to familiarize radiologists with translabial ultrasound technique and provide a technical protocol for TLUS execution because it can be optimized for imaging and assessment of MUS, including identification of MUS configuration and recognition of common complications. This article provides example images of transobturator and retropubic slings and their associated complications, as visualized on TLUS. Accurate imaging and assessment of MUS is helpful in the evaluation of the patient presenting with symptoms suspicious for sling-related complications and in the planning of surgical revision.
Magnetic Resonance Prediction of Lung Maturity in Fetuses With Congenital Diaphragmatic Hernia
Authors: Wiggins Eve , Zecevic Mladen , Hippe Dan S. , Moshiri Mariam , Winter Tom , Dubinsky Theodore J.
Published: September 2021

To determine if lung to liver MR T2 signal ratio is predictive of neonatal outcome in fetuses with congenital diaphragmatic hernia (CDH).

After Interal Review Board approval, the PACS systems at the University of Washington and University of Utah were searched for cases having an in utero fetal MR examination diagnostic of CDH. Inclusion criteria were at least 1 prior ultrasound demonstrating a CDH and an MR obtained within 1 week of that prior ultrasound.

A total of 69 patients from the University of Utah and 13 from the University of Washington satisfied the inclusion criteria for a total of 82. After adjusting for gestational age and contralateral lung volume, there was little apparent association between contralateral lung to liver MR T2 signal and 5-minute Apgar score and neonatal mortality When considering neonatal Apgar and mortality, increasing contralateral lung volume was significantly associated with lower risk (hazard ratio, 0.40 per doubling; 95% confidence interval, 0.24–0.69; P = 0.001) as expected.

Our data demonstrate that the lung to liver MR signal ratio was not predictive of outcome. The measurement of contralateral lung area, and gestational age at the time of the examination (time of diagnosis) are still the best predictors of poor neonatal outcome.
Behavioral Assessment of Patients With Disorders of Consciousness
Authors: Fitzpatrick-DeSalme Eileen , Long Angela , Patel Ferzeen , Whyte John
Published: September 2021

Brain injury resulting in coma may evolve into a prolonged disorder of consciousness, including the vegetative and minimally conscious states. Early detection of emerging consciousness has positive prognostic significance, and improvement in consciousness at any point may indicate the potential for meaningful communication and environmental control. Despite the importance of accurate assessment of consciousness, research indicates that as many as 40% of patients with a disorder of consciousness may be assessed incorrectly. Assessment of consciousness is challenging for many reasons, including the fact that consciousness cannot be measured directly but must be inferred from patterns of behavioral activity, that many patients have confounding deficits and treatments that may mask consciousness, and that patient performance may be highly variable over time. In this manuscript, we discuss strategies for optimizing patient status during assessment and review a number of structured assessment approaches that can be used. The available assessment techniques vary in their length and cost, and the expertise required to use them. Which of these approaches is most applicable to a given acute or subacute setting will vary with the volume of patients with a disorder of consciousness and the available resources. Importantly, lack of consciousness in the acute setting should not be used to justify the withdrawal of care or denial of rehabilitation services.
Metagenomic evidence for a polymicrobial signature of sepsis
Authors: Tan Cedric Chih Shen , Acman Mislav , van Dorp Lucy , Balloux Francois
Published: September 2021

Our understanding of the host component of sepsis has made significant progress. However, detailed study of the microorganisms causing sepsis, either as single pathogens or microbial assemblages, has received far less attention. Metagenomic data offer opportunities to characterize the microbial communities found in septic and healthy individuals. In this study we apply gradient-boosted tree classifiers and a novel computational decontamination technique built upon SHapley Additive exPlanations (SHAP) to identify microbial hallmarks which discriminate blood metagenomic samples of septic patients from that of healthy individuals. Classifiers had high performance when using the read assignments to microbial genera [area under the receiver operating characteristic (AUROC=0.995)], including after removal of species ‘culture-confirmed’ as the cause of sepsis through clinical testing (AUROC=0.915). Models trained on single genera were inferior to those employing a polymicrobial model and we identified multiple co-occurring bacterial genera absent from healthy controls. While prevailing diagnostic paradigms seek to identify single pathogens, our results point to the involvement of a polymicrobial community in sepsis. We demonstrate the importance of the microbial component in characterising sepsis, which may offer new biological insights into the aetiology of sepsis, and ultimately support the development of clinical diagnostic or even prognostic tools.
Opt-out policies capacity to increase organ donors is limited
Authors: Molina Pérez Alberto , Rodríguez-Arias David , Delgado Janet
Published: September 2021

Objectives: To increase post-mortem organ donation rates, several countries are adopting an opt-out (presumed consent) policy, meaning that individuals are deemed donors unless they expressly refused so. However, studies on the relative impact of opt-in or opt-out on deceased organ donation rates are inconclusive. Although opt-out countries tend to have higher donation rates, there is no conclusive evidence that this is caused by the policy itself. The main objective of this study is to better assess the impact of consent policies when considering the role of the family in decision-making.

Design: By systematically combining the three components of the decision-making process --the default rule, the deceaseds preferences, and the family s preferences,-- we identify all situations that affect the retrieval outcome under opt-in and opt-out policies. Then, by gathering empirical data from a wide array of countries, we estimate the relative frequency of these situations.

Main outcome measures: We measure the relative impact that opt-in and opt-out policies have per se on post-mortem organ retrieval.

Results: Our analysis shows that opt-in and opt-out have strictly identical outcomes in eight out of nine situations. These policies only differ when neither the deceased nor the family have expressed a preference and defaults therefore apply. The actual impact of consent policies is typically circumscribed to a range of 0% to 5% of all opportunities for organ retrieval.

Conclusions: This study may warn contemporary organ retrieval policymakers that, by emphasizing the need to introduce presumed consent, they might be overestimating the influence of policy defaults and underestimating the power granted to families in expressing their preferences and making decisions about organ donation. Governments should reassess the opportunity and effectiveness of adopting opt-out policies for organ retrieval.