Fatal Moans and Bones in Crohn's: A Case of Heterotopic Mesenteric Ossification.

ABSTRACT: Heterotopic mesenteric ossification (HMO) represents a rare reactive condition characterized by abnormal bone formation within the mesentery. HMO's etiology remains enigmatic, with proposed triggers including trauma-induced metaplasia or bone fragment dislodgment from other sites during abdominal surgery. With fewer than 100 documented cases in the literature, much about this condition remains unknown. In this report, we present a notable case of HMO in a 43-year-old man with a history of severe Crohn's disease and multiple abdominal surgeries. Following a period of unresponsiveness at home, he was admitted to the intensive care unit, where he received palliative care due to a poor prognosis. An autopsy revealed mature, benign bone fragments within the mesentery, alongside severe dehydration, likely exacerbated by decreased oral intake and medication cessation related to his ostomy. Although antemortem imaging revealed HMO, it was misattributed to contrast versus calcification. This case underscores the importance of clinician awareness regarding HMO, particularly its potential implications in inflammatory bowel disease. Early recognition and interdisciplinary collaboration among radiologists, pathologists, and clinicians are paramount in optimizing patient outcomes. Further research is warranted to elucidate this intriguing pathology's pathogenesis and best management strategies.

How (Cautious) Social Media Use May Improve Education and Pipeline Efforts of a Growing Postpandemic Forensic Pathologist Workforce Shortage.

ABSTRACT: Many subspecialties of pathology have initiated novel methods and strategies to connect with medical students and residents, stimulate interest, and offer mentorship. Emerging concern about the future of forensic pathology has been highlighted in contemporary literature as recruitment of new fellows has stagnated and workforce shortage concerns have blossomed. Amidst these challenges, the potential role of social networking platforms like social media (SoMe) in enhancing autopsy pathology/forensics education has garnered attention, yet literature focusing specifically on its application in autopsy and forensic pathology remains limited. This review aims to provide a comprehensive narrative overview of the current literature on the established uses of SoMe in forensic pathology. It seeks to build upon existing recommendations, introducing a contemporary compilation of online resources designed to facilitate virtual engagement among pathologists, learners, patients, and families. The review supports the idea that strategic, ethical, and conscientious use of SoMe has a place in addressing the growing workforce shortages and closing educational gaps in forensic pathology by enhancing exposure to the field and dispelling antiquated stereotypes.

Association of Upper Respiratory Streptococcus pneumoniae Colonization With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Adults.

BACKGROUND: Streptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We collected saliva specimens from working-age adults undergoing SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. After bacterial culture enrichment, we tested for pneumococci by means of quantitative polymerase chain reaction targeting the lytA and piaB genes, and we measured associations with SARS-CoV-2 infection using conditional logistic regression. RESULTS: Analyses included 1278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. The prevalence of pneumococcal carriage was 9.2% (117 of 1278) among all participants (11.2% [63 of 564] in clinic-based testing and 7.6% [54 of 714] in outreach-based testing). The prevalence of SARS-CoV-2 infection was 27.4% (32 of 117) among pneumococcal carriers and 9.6% (112 of 1161) among noncarriers (adjusted odds ratio [aOR], 2.73 [95% confidence interval (CI): 1.58-4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR, 4.01 [95% CI: 2.08-7.75]) and among symptomatic participants (3.38 [1.35-8.40]), compared with findings within the outreach-based sample and among asymptomatic participants. The adjusted odds of SARS-CoV-2 coinfection increased 1.24-fold (95% CI: 1.00-1.55-fold) for each 1-unit decrease in piaB quantitative polymerase chain reaction cycle threshold value among pneumococcal carriers. Finally, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected coronavirus disease 2019 case (aOR, 7.64 [95% CI: 1.91-30.7] and 3.29 [1.94-5.59]) among pneumococcal carriers and noncarriers, respectively). CONCLUSIONS: Associations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2.

Are committee experiences of minoritized family medicine faculty part of the minority tax? a qualitative study.

BACKGROUND AND OBJECTIVES: Because much of the work in academic medicine is done by committee, early career URiM faculty, are often asked to serve on multiple committees, including diversity work that may not be recognized as important. They may also be asked to serve on committees to satisfy a diversity "check box," and may be asked more often than their non-URiM peers to serve in this capacity. We sought to describe the committee experiences of early career URiM faculty, hypothesizing that they may see committee service as a minority tax. METHODS: Participants in the Leadership through Scholarship Fellowship (LTSF) were asked to share their experiences with committee service in their careers after participating in a faculty development discussion. Their responses were analyzed and reported using qualitative, open, axial, and abductive reasoning methods. RESULTS: Four themes, with eight sub-themes (in parenthesis), emerged from the content analysis of the LTSF fellows responses to the prompt: Time commitment (Timing of committee work and lack of protected time for research and scholarship), URiM Committee service (Expectation that URiM person will serve on committees and consequences for not serving), Mentoring issues (no mentoring regarding committee service, faculty involvement is lacking and the conflicting nature of committee work) and Voice (Lack of voice or acknowledgement). CONCLUSIONS: Early career URiM faculty reported an expectation of serving on committees and consequences for not serving related to their identity, but other areas of committee service they shared were not connected to their URiM identity. Because most of the experiences were not connected to the LTSF fellows' URiM identity, this group has identified areas of committee service that may affect all early career faculty. More research is necessary to determine how committee service affects URiM and non-URiM faculty in academic family medicine.

Intravascular Large B-cell Lymphoma Presenting as Sudden Death.

ABSTRACT: Intravascular large B-cell lymphoma is a rare subset of non-Hodgkin lymphoma composed of mature B lymphoma cells confined to the intravascular space. This disease remains elusive because it lacks a discrete tumor mass, can affect any part of the body, and has vague symptoms paired with heterogeneous clinical findings resulting in delayed or missed accurate diagnosis, even at postmortem examination. This is a case of a woman who died within hours of presenting to the emergency department with a diagnosis of intravascular large B-cell lymphoma made through autopsy examination, adding to the knowledge of this rare disease and bringing it to the attention of practicing autopsy and forensic pathologists.

Smoking Cessation Interventions.

In the United States, 1 in 5 adults uses tobacco products. Cigarette smoking is the leading cause of preventable disease and death in the United States despite its known health effects. Although nearly one-half of people who smoke try to quit each year, only up to 1 in 20 who quit without support achieve abstinence for at least six months. All patients, including school-aged children and adolescents, should be asked if they smoke and offered evidence-based treatments for smoking cessation. Use of the 5 A's framework (ask, advise, assess, assist, arrange) can help clinicians promote smoking cessation. Clinical studies have demonstrated that combining pharmacotherapy with effective behavior strategies is significantly more effective than either approach alone. Pharmacotherapies approved by the U.S. Food and Drug Administration for smoking cessation include nicotine replacement therapy, bupropion, and varenicline. Extended use (greater than 12 weeks) of a controller therapy (varenicline, bupropion, or nicotine patch) is associated with significantly higher sustained quit rates and lower relapse rates than standard use (six to 12 weeks). e-Cigarettes are not approved by the U.S. Food and Drug Administration for smoking cessation, and evidence supporting their benefit is inconclusive. Lung cancer screening is recommended for adults 50 to 80 years of age who have a 20-pack-year smoking history and currently smoke or have quit within the past 15 years. Lung cancer screening should be combined with smoking cessation tools and treatment.

Wall Falls: Blunt Trauma Sustained from Border Wall Crossings.

ABSTRACT: The border wall between the United States and Mexico consists of stretches of metal fencing of varying heights alternating and overlapping with areas of electronic surveillance. Despite national conversations centered around the social, environmental, economic, and political implications of this wall, there is a paucity of studies on deaths occurring in this region. Herein are described 2 cases of fatal injuries sustained from scaling the fence and accidentally falling onto the United States' side in New Mexico. These injuries are compared with those typically incurred in falls from lower and higher heights, and implications of both lateral and vertical expansion of the wall are discussed.

New Mexico's COVID-19 Experience.

ABSTRACT: The 2019 novel coronavirus disease (COVID-19) has spread worldwide, infiltrating, infecting, and devastating communities in all locations of varying demographics. An overwhelming majority of published literature on the pathologic findings associated with COVID-19 is either from living clinical cohorts or from autopsy findings of those who died in a medical care setting, which can confound pure disease pathology. A relatively low initial infection rate paired with a high biosafety level enabled the New Mexico Office of the Medical Investigator to conduct full autopsy examinations on suspected COVID-19-related deaths. Full autopsy examination on the first 20 severe acute respiratory syndrome coronavirus 2-positive decedents revealed that some extent of diffuse alveolar damage in every death due to COVID-19 played some role. The average decedent was middle-aged, male, American Indian, and overweight with comorbidities that included diabetes, ethanolism, and atherosclerotic and/or hypertensive cardiovascular disease. Macroscopic thrombotic events were seen in 35% of cases consisting of pulmonary thromboemboli and coronary artery thrombi. In 2 cases, severe bacterial coinfections were seen in the lungs. Those determined to die with but not of severe acute respiratory syndrome coronavirus 2 infection had unremarkable lung findings.

An Unusual Method of Suicide: Cable Ties.

Suicidal ligature strangulation is a relatively rare event-far more common is suicide by hanging or homicidal ligature strangulation. With the increasing rate of suicide in the United States, use of atypical ligatures is likely to increase as well. Herein, we present such a rare case, a man who died by tightening cable ties around his own neck, and discuss the necessity of full scene and autopsy investigation to ensure proper certification of manner of death.

Surgical intervention for vertebral osteomyelitis in a calf.

OBJECTIVE: To report the surgical treatment and outcome of a non-ambulatory calf with cervical vertebral ostoeomyelitis. STUDY DESIGN: Clinical report. SAMPLE POPULATION: One 3.5-month-old female mixed-breed calf with tetraparesis of 3 months duration. METHODS: After computed tomography-guided bone biopsy, a bacterial osteolytic lesion within the body of the fourth cervical vertebrae (C4) and resultant pathologic compression fracture clinically resulting in full tetraparesis was diagnosed in the calf. Culture results from the lesion within C4 confirmed a diagnosis of Trueperella pyogenes. RESULTS: Poor response to medical management justified surgical debridment of the lesion in C4 and subsequent stabilization of the cervical vertebral column. A three-part procedure was performed including (1) debridement of the C4, (2) bilateral ventral vertebral stabilization from C3 to C5, and (3) placement of ampicillin-impregnated plaster of Paris beads within the body of C4. With postoperative physical rehabilitation, the calf regained full ambulatory function. At 1-month follow-up, the calf remained ambulatory with mild proprioceptive ataxia and no evidence of implant failure. At annual recheck, the calf had gained 208 kg and remained fully ambulatory with no residual neurologic deficits. CONCLUSION: Surgical intervention and use of antibiotic-impregnated implants offered a viable alternative to long-term medical management of vertebral osteomyelitis in the calf reported here. CLINICAL SIGNIFICANCE: This case identifies surgical intervention as a potential means for improving outcomes in a historically fatal condition of production animals.

Discovery and development of new antibacterial drugs: learning from experience?

Antibiotic (antibacterial) resistance is a serious global problem and the need for new treatments is urgent. The current antibiotic discovery model is not delivering new agents at a rate that is sufficient to combat present levels of antibiotic resistance. This has led to fears of the arrival of a 'post-antibiotic era'. Scientific difficulties, an unfavourable regulatory climate, multiple company mergers and the low financial returns associated with antibiotic drug development have led to the withdrawal of many pharmaceutical companies from the field. The regulatory climate has now begun to improve, but major scientific hurdles still impede the discovery and development of novel antibacterial agents. To facilitate discovery activities there must be increased understanding of the scientific problems experienced by pharmaceutical companies. This must be coupled with addressing the current antibiotic resistance crisis so that compounds and ultimately drugs are delivered to treat the most urgent clinical challenges. By understanding the causes of the failures and successes of the pharmaceutical industry's research history, duplication of discovery programmes will be reduced, increasing the productivity of the antibiotic drug discovery pipeline by academia and small companies. The most important scientific issues to address are getting molecules into the Gram-negative bacterial cell and avoiding their efflux. Hence screening programmes should focus their efforts on whole bacterial cells rather than cell-free systems. Despite falling out of favour with pharmaceutical companies, natural product research still holds promise for providing new molecules as a basis for discovery.

EGFR-mediated apoptosis via STAT3.

The Epidermal Growth Factor Receptor (EGFR) is a cell surface receptor with primary implications in cell growth in both normal and malignant tissue. Paradoxically, cell lines that hyperexpress the EGFR have been documented to undergo receptor-mediated apoptosis. The underlying mechanism by which EGF-induced apoptosis occurs however remains inexplicit. In an attempt to identify this mechanism, we assessed downstream effectors of EGFR in MDA-MB-468 cells during conditions of EGF-induced apoptosis. The effector assessment revealed STAT3 as a potential mediator of EGF-induced apoptosis. Alternative strategies for activating STAT3, independent of EGFR stimulation, resulted in the induction of the apoptotic pathways. A reduction in STAT3 expression via RNAi resulted in a significant attenuation of EGF-induced PARP cleavage. Our findings support STAT3 as a positive mediator of EGF-induced apoptosis in MDA-MB-468 cells.

The beliefs and willingness of men who have sex with men to comply with a one-year blood donation deferral policy: a cross-sectional study.

BACKGROUND: In 2016, the US Food and Drug Administration ended the lifetime blood donation deferral for men who have sex with men (MSM) and replaced it with a 1-year deferral period. It is currently unknown how many MSM may meet the new deferral policy and how many are willing to comply with it. STUDY DESIGN AND METHODS: An anonymous survey was shared on MSM-focused social media sites between May and July 2016 and enrolled self-identified American MSM who were at least 18 years old. The survey assessed the willingness of MSM to donate blood, donation history, and knowledge regarding current blood donation needs and testing limitations. RESULTS: A total of 764 men met criteria to be included in the final data set. Only 8.9% (95% confidence interval [CI], 6.9%-10.9%) met the current 12-month deferral criteria, yet 90.6% (95% CI, 88.5%-92.7%) were interested in donating. Among men interested in donating blood, 57.9% (95% CI, 54.3%-61.4%) would consider donating blood without meeting the 12-month deferral criteria. Overall, 26.7% (95% CI, 23.6%-29.8%) admitted to donating blood at least once in the past despite not meeting deferral criteria. CONCLUSIONS: Few MSM met the current deferral criteria, yet many were interested in donating, even without meeting deferral criteria. Possible motivations to donate without meeting deferral criteria may include a perceived shortage of donated blood and infallibility of current blood testing technology to detect human immunodeficiency virus. If the current 1-year deferral is maintained, it is essential that there is outreach to the MSM community to explain and educate why this policy exists.

Protein Kinase G facilitates EGFR-mediated cell death in MDA-MB-468 cells.

The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase with critical implications in cell proliferation, migration, wound healing and the regulation of apoptosis. However, the EGFR has been shown to be hyper-expressed in a number of human malignancies. The MDA-MB-468 metastatic breast cell line is one example of this. This particular cell line hyper-expresses the EGFR and undergoes EGFR-mediated apoptosis in response to EGF ligand. The goal of this study was to identify the kinases that could be potential intermediates for the EGFR-mediated induction of apoptosis intracellularly. After identifying Cyclic GMP-dependent Protein Kinase G (PKG) as a plausible intermediate, we wanted to determine the temporal relationship of these two proteins in the induction of apoptosis. We observed a dose-dependent decrease in MDA-MB-468 cell viability, which was co-incident with increased PKG activity as measured by VASPSer239 phosphorylation. In addition, we observed a dose dependent decrease in cell viability, as well as an increase in apoptosis, in response to two different PKG agonists, 8-Bromo-cGMP and 8-pCPT-cGMP. MDA-MB-468 cells with reduced PKG activity had attenuated EGFR-mediated apoptosis. These findings indicate that PKG does not induce cell death via transphosphorylation of the EGFR. Instead, PKG activity occurs following EGFR activation. Together, these data indicate PKG as an intermediary in EGFR-mediated cell death, likely via apoptotic pathway.

Pathology Image Of the Month: Rapidly Progressive Hemorrhagic Cellulitis of Bilateral Lower Extremities with Subsequent Septic Shock and Death.

A 51-year-old man presented to a community based emergency department with bilateral lower extremity swelling that began four days prior and that had evolved into recent blister formation on the left lower extremity. Medical history was significant only for hypertension and a recent self-described episode of "food poisoning" five days earlier characterized by diarrhea, nausea, and vomiting that quickly resolved. Physical exam revealed marked bilateral lower extremity edema and an ecchymotic rash below the knee. In addition to the rash, there were large flaccid bullae on the left leg, mostly intact but some notable for draining of scanty serosanguinous fluid. The patient was tachycardic with a rate of 114 bpm and initial labs showed thrombocytopenia (platelets 56 x 103/uL [140-440 x 103/uL]), hypoglycemia (15mg/dl [70-105mg/dl]), an elevated creatinine (2.7mg/dL [0.7- 1.25mg/dL]), and aspartate aminotransferase (AST 156U/L [5- 34U/L]). Two sets of blood cultures were drawn, broad spectrum antibiotics including doxycycline were empirically initiated and then he was subsequently transported to a tertiary care hospital for escalation of care. Within hours of presentation to the tertiary care facility, the rash appeared progressively hemorrhagic and bullous, lactic acidosis and coagulopathy developed and hemodynamic instability and septic shock necessitated endotracheal intubation and vasopressors. He was taken to the operating room for skin debridement but was emergently converted to bilateral above the knee lower extremity amputations due to the extent of the soft tissue necrosis. The patient remained intubated and in critical condition following surgery and the ecchymotic rash reappeared at the amputation sites. A newly developed ecchymotic rash with bullae formation was noted on the right upper extremity forearm. At that time, the clinicians were notified that four out of four blood culture bottles from admission were rapidly growing a microorganism. The family elected for withdrawal of care, and the patient died approximately 72 hours following presentation. A full and unrestricted autopsy was authorized by the Coroner's Office.

Silver resistance in Gram-negative bacteria: a dissection of endogenous and exogenous mechanisms.

OBJECTIVES: To gain a more detailed understanding of endogenous (mutational) and exogenous (horizontally acquired) resistance to silver in Gram-negative pathogens, with an emphasis on clarifying the genetic bases for resistance. METHODS: A suite of microbiological and molecular genetic techniques was employed to select and characterize endogenous and exogenous silver resistance in several Gram-negative species. RESULTS: In Escherichia coli, endogenous resistance arose after 6 days of exposure to silver, a consequence of two point mutations that were both necessary and sufficient for the phenotype. These mutations, in ompR and cusS, respectively conferred loss of the OmpC/F porins and derepression of the CusCFBA efflux transporter, both phenotypic changes previously linked to reduced intracellular accumulation of silver. Exogenous resistance involved derepression of the SilCFBA efflux transporter as a consequence of mutation in silS, but was additionally contingent on expression of the periplasmic silver-sequestration protein SilE. Silver resistance could be selected at high frequency (>10(-9)) from Enterobacteriaceae lacking OmpC/F porins or harbouring the sil operon and both endogenous and exogenous resistance were associated with modest fitness costs in vitro. CONCLUSIONS: Both endogenous and exogenous silver resistance are dependent on the derepressed expression of closely related efflux transporters and are therefore mechanistically similar phenotypes. The ease with which silver resistance can become selected in some bacterial pathogens in vitro suggests that there would be benefit in improved surveillance for silver-resistant isolates in the clinic, along with greater control over use of silver-containing products, in order to best preserve the clinical utility of silver.

From intimate partners to serial killers: Nearly 40 years of female homicides in King County, Washington (1978-2016).

An extreme, known potential outcome of intimate partner violence (IPV) is death, with national data revealing females are more likely to be killed by intimate partners than by others. In a novel pairing, the King County Medical Examiner's Office data management system and the Washington State Attorney General's Office's Homicide Information Tracking System were retrospectively analyzed (1978-2016) with information gathered pertaining to female homicide victims. Analyses show that female victims commonly knew their assailant(s) (79.3%) who were overwhelmingly male (92.8%) and commonly intimate partners (31.4%). Disproportionately represented were Black (20.17%) and Native American (4.25%) females; Asian/Pacific Islander (2.5 times that of Whites) and elderly (24%) females among homicide-suicide deaths; and Asian/Pacific Islander and Hispanic females in cases of IPV. "Domestic violence" was the most cited motive (34.3%) and most assaults occurred in a residence (58.73%). Females under 10 years of age were most commonly killed by a parent or caregiver (42.86%), while those over 70 were most likely to be killed by a child (23.08%) or spouse (21.80%). Serial murders, most commonly by the Green River Killer (80%) but including others, accounted for at least 7% of deaths, with victims notably young and commonly sex workers (68%). As compared to males, females were more likely to be killed by multiple modalities, asphyxia, and sharp force, though IPV-related deaths were more likely to be associated with firearms. This study reinforces the vulnerability of females to IPV, sexual assault, and serial murders as well as to caretakers at the extremities of age.

Justice-Involved Youth: Support for Community and Family Interventions.

Justice-involved youth have high rates of mental health symptoms and diagnoses. Unaddressed mental health needs are associated with exposure to adversity and trauma, as well as unidentified or mislabeled symptoms that may be present early in life. Justice-involved youth disproportionately come from low-income families and minoritized populations. Community-based interventions that address family and community factors associated with justice involvement are key to improving mental health and life trajectory outcomes for youth. Policies and interventions that address unmet educational needs, support families, and promote early identification of youth in need of social, educational, and mental health services are reviewed.

Health disparities among incarcerated populations: a crucial laboratory and pathology review.

BACKGROUND: The United States notoriously has one of the highest rates of incarceration in the world, yet scant attention to the health care needs of those incarcerated exists within laboratory medicine and pathology training and education. This article explores health disparities among incarcerated and released individuals regarding diagnostic laboratory testing and pathology services. METHODS: A literature search was conducted for articles published between 2002 and 2023 using keywords including "healthcare," "incarcerated," "laboratory services," "pathology services," and "health insurance for prisoners." Central themes were extracted and discussed to reveal the realities of health care during and after release from incarceration. Excluded from the analysis were articles about the immediate or extended family of incarcerated persons. RESULTS: Incarcerated individuals have an increased risk for the development and exacerbation of communicable and noncommunicable diseases and mental health disorders, which results in exceedingly high morbidity and mortality rates. CONCLUSION: Policy changes are needed to mitigate disparities and improve health outcomes for incarcerated and released persons. Central to these disparities is decreased access to laboratory and pathology services, impeded by inadequate health care funding for these carceral institutions. Providing additional funding to the carceral system's health care budget is necessary to improve access to pathology and laboratory services.