Characteristics of Cancers in Community Members Exposed to the World Trade Center Disaster at a Young Age.

The destruction of the World Trade Center (WTC) towers on 11 September 2001 (9/11) released tons of dust and smoke into the atmosphere, exposing hundreds of thousands of community members (survivors) and responders to carcinogens. The WTC Environmental Health Center (WTC EHC) is a federally designated surveillance and treatment program for community members who were present in the New York City disaster area on 9/11 or during the months that followed. WTC EHC enrollment requires exposure to the WTC dust and fumes and a federally certifiable medical condition, which includes most solid and blood cancers. Several studies have described the prevalence and characteristics of cancers in responders and survivors exposed to the WTC dust and fumes as adults. Cancers in those exposed at a young age warrant specific investigation since environmental toxin exposure at a younger age may change cancer risk. We describe the characteristics of 269 cancer patients with 278 cancer diagnoses among WTC EHC enrollees who were young in age (aged 0 to 30) on 9/11. These include 215 patients with a solid tumor (79.9%) and 54 with a lymphoid and/or hematopoietic cancer (20.1%). Among them, 9 patients had a known second primary cancer. A total of 23 different types of cancer were identified, including cancer types rare for this age group. Many were diagnosed in individuals lacking traditional cancer-specific risk factors such as tobacco use. The current study is the first to report specifically on cancer characteristics of younger enrollees in the WTC EHC program.

Characteristics of Women with Lung Adenocarcinoma in the World Trade Center Environmental Health Center.

The destruction of the World Trade Center towers on 11 September 2001 exposed local residents, workers, and individuals in the area (Survivors) to dust and fumes that included known and suspected carcinogens. Given the potential for inhalation of toxic substances and the long latency after exposure, the incidence of lung cancer is expected to increase in WTC-exposed individuals. We describe the characteristics of women WTC Survivors with lung adenocarcinoma who were enrolled in the WTC Environmental Health Center (WTC EHC) between May 2002 and July 2021. A total of 173 women in WTC EHC had a diagnosis of any type of lung cancer, representing 10% of all cancers in women. Most of the lung cancers (87%) were non-small cell carcinomas, with adenocarcinoma (77%) being the most common subtype. Nearly half (46%) of these patients were exposed to dust clouds on 11 September 2001. Race and ethnicity varied by smoking status, as follows: 44% of Asian women compared with 29% of non-Hispanic White women were never-smokers (p < 0.001). There was no significant difference between the pathologic characteristics of adenocarcinomas between never and ever smokers. We also summarize EGFR, ALK, KRAS, ROS-1 and BRAF mutation status stratified by smoking, race and ethnicity. The identification of a relatively high proportion of women never-smokers with lung cancer warrants further investigation into the role of WTC dust exposure.

Molecular Clustering Analysis of Blood Biomarkers in World Trade Center Exposed Community Members with Persistent Lower Respiratory Symptoms.

The destruction of the World Trade Center (WTC) on September 11, 2001 (9/11) released large amounts of toxic dusts and fumes into the air that exposed many community members who lived and/or worked in the local area. Many community members, defined as WTC survivors by the federal government, developed lower respiratory symptoms (LRS). We previously reported the persistence of these symptoms in patients with normal spirometry despite treatment with inhaled corticosteroids and/or long-acting bronchodilators. This report expands upon our study of this group with the goal to identify molecular markers associated with exposure and heterogeneity in WTC survivors with LRS using a selected plasma biomarker approach. Samples from WTC survivors with LRS (n = 73, WTCS) and samples from healthy control participants of the NYU Bellevue Asthma Registry (NYUBAR, n = 55) were compared. WTCS provided information regarding WTC dust exposure intensity. Hierarchical clustering of the linear biomarker data identified two clusters within WTCS and two clusters within NYUBAR controls. Comparison of the WTCS clusters showed that one cluster had significantly increased levels of circulating matrix metalloproteinases (MMP1, 2, 3, 8, 12, 13), soluble inflammatory receptors (receptor for advanced glycation end-products-RAGE, Interleukin-1 receptor antagonist (IL-1RA), suppression of tumorigenicity (ST)2, triggering receptor expressed on myeloid cells (TREM)1, IL-6Ra, tumor necrosis factor (TNF)RI, TNFRII), and chemokines (IL-8, CC chemokine ligand- CCL17). Furthermore, this WTCS cluster was associated with WTC exposure variables, ash at work, and the participant category workers; but not with the exposure variable WTC dust cloud at 9/11. A comparison of WTC exposure categorial variables identified that chemokines (CCL17, CCL11), circulating receptors (RAGE, TREM1), MMPs (MMP3, MMP12), and vascular markers (Angiogenin, vascular cell adhesion molecule-VCAM1) significantly increased in the more exposed groups. Circulating biomarkers of remodeling and inflammation identified clusters within WTCS and were associated with WTC exposure.

Breast Cancer Characteristics in the Population of Survivors Participating in the World Trade Center Environmental Health Center Program 2002-2019.

The destruction of World Trade Center on 11 September 2001 exposed local community members to a complex mixture of known carcinogens and potentially carcinogenic substances. To date, breast cancer has not been characterized in detail in the WTC-exposed civilian populations. The cancer characteristics of breast cancer patients were derived from the newly developed Pan-Cancer Database at the WTC Environmental Health Center (WTC EHC). We used the Surveillance, Epidemiology, and End Results (SEER) Program breast cancer data as a reference source. Between May 2002 and 31 December 2019, 2840 persons were diagnosed with any type of cancer at the WTC EHC, including 601 patients with a primary breast cancer diagnosis (592 women and 9 men). There was a higher proportion of grade 3 (poorly differentiated) tumors (34%) among the WTC EHC female breast cancers compared to that of the SEER-18 data (25%). Compared to that of the SEER data, female breast cancers in the WTC EHC had a lower proportion of luminal A (88% and 65%, respectively), higher proportion of luminal B (13% and 15%, respectively), and HER-2-enriched (5.5% and 7%, respectively) subtypes. These findings suggest considerable differences in the breast cancer characteristics and distribution of breast cancer intrinsic subtypes in the WTC-exposed civilian population compared to that of the general population. This is important because of the known effect of molecular subtypes on breast cancer prognosis.

Lung Cancer Characteristics in the World Trade Center Environmental Health Center.

The destruction of the World Trade Center (WTC) towers on 11 September 2001 resulted in acute and chronic dust and fume exposures to community members, including local workers and residents, with well-described aerodigestive adverse health effects. This study aimed to characterize lung cancer in the WTC Environmental Health Center (WTC EHC) focusing on gender and smoking history. WTC EHC patients undergo an initial evaluation that includes WTC exposure information, demographics, and tobacco use. Detailed cancer characteristics are recorded from pathology reports. As of 31 December 2019, 248 WTC EHC patients had a diagnosis of lung cancer. More patients with lung cancer were women (57%) compared to men (43%). Many cases (47% women, 51% men) reported acute dust cloud exposure. Thirty-seven percent of lung cancer cases with available smoking history were never-smokers (≤1 pack-years) and 42% had a ≤5 pack-year history. The median age of cancer diagnosis in never-smoking women was 61 years compared to 66 years in men. Adenocarcinoma was more common in never-smokers compared to ever-smokers (72% vs. 65%) and in women compared to men (70% vs. 65%). We provide an initial description of lung cancers in local community members with documented exposure to the WTC dust and fumes.

The Development of a WTC Environmental Health Center Pan-Cancer Database.

(1) Background: Recent studies have reported elevated risks of multiple cancers in the World Trade Center (WTC) affected community members (also called WTC "Survivors"). The large variety of WTC-cancers created a need to develop a comprehensive cancer database. This paper describes the development of a pan-cancer database at the WTC Environmental Health Center (EHC) Data Center. (2) Methods: A new REDCap-based pan-cancer database was created using the pathology reports and available biomarker data of confirmed cancer cases after review by a cancer epidemiologist, a pathologist, physicians and biostatisticians. (3) Results: The WTC EHC pan-cancer database contains cancer characteristics and emerging biomarker information for cancers of individuals enrolled in the WTC EHC and diagnosed after 11 September 2001 and up to 31 December 2019 obtained from WTC EHC clinical records, pathological reports and state cancer registries. As of 31 December 2019, the database included 3440 cancer cases with cancer characteristics and biomarker information. (4) Conclusions: This evolving database represents an important resource for the scientific community facilitating future research about the etiology, heterogeneity, characteristics and outcomes of cancers and comorbid mental health conditions, cancer economics and gene-environment interaction in the unique population of WTC survivors.

Characteristics of Cancer Patients in the World Trade Center Environmental Health Center.

The destruction of the World Trade Center (WTC) towers on 11 September 2001 released many tons of aerosolized dust and smoke with potential for carcinogenic exposures to community members as well as responders. The WTC Environmental Health Center (WTC EHC) is a surveillance and treatment program for a diverse population of community members ("Survivors"), including local residents and workers, present in the NYC disaster area on 9/11 or in the days or weeks following. We report a case series of cancers identified in the WTC EHC as of 31 December 2019. Descriptive characteristics are presented for 2561 cancer patients (excluding non-melanoma skin cancer) and 5377 non-cancer WTC-EHC participants who signed informed consent. We identified a total of 2999 cancer diagnoses in 2561 patients: 2534 solid tumors (84.5%) and 465 lymphoid and hematopoietic tissue cancers (15.5%) with forty-one different cancer types. We describe the distribution, frequency, median age of cancer diagnosis and median latency from 9/11 by cancer site. In addition to common cancer types, rare cancers, including male breast cancers and mesotheliomas have been identified. The current study is the first report on cancer characteristics of enrollees at WTC EHC, a federally designated treatment and surveillance program for local community members affected by the 9/11 terrorist attack on the WTC.

Histopathological evaluation of autopsy cases with isolated pulmonary fat embolism (IPFE): is cardiopulmonary resuscitation a main cause of death in IPFE?

Background: Fat embolism (FE) may develop following many traumatic and atraumatic clinical conditions; however, fewer data exist regarding the occurrence of isolated pulmonary FE (IPFE). Cardiopulmonary resuscitation (CPR) is an emergency procedure for maintaining blood circulation and oxygenation during cardiac arrest. In this study, we aimed to evaluate the association of CPR with IPFE in autopsy cases. Methods: A total 402 cases among 4,118 autopsies were diagnosed with IPFE, and the medical background of these cases was retrospectively evaluated. Diagnosis of FE and FE grading were performed with histopathological examinations of postmortem tissue samples, and injury-severity scores of traumatic cases were assessed. Data of traumatic and atraumatic cases were statistically compared. Results: Of the IPFE cases, 298 (741%) were male and 104 (25.9%) female, with overall mean age 53.7 (2-99) years. Causes of death of studied subjects were traumatic for 302 (75.1%) and atraumatic reasons for 100 (24.9%) cases. CPR was performed for 277 cases of which 177 (63.9%) were traumatic and 100 (36.1%) were non-traumatic. In comparison to traumatic cases, significantly higher CPR frequency was determined in atraumatic IPFE (P=0.001). High grade FE in the traumatic cases, and mild-moderate grade of FE in the nontraumatic cases were found statistically significant (P=0.001). Conclusion: This study indicates that CPR may be one of the leading factors in the development of IPFE in atraumatic conditions, and this procedure was related to mild-moderate IPFE manifestations. Regardless of whether conditions were traumatic or atraumatic, in patients who survive following CPR for manifest ventilation/perfusion problems, it should be remembered that IPFE may have developed due to CPR.

Coenzyme Q10 improves the survival, mesenteric perfusion, organs and vessel functions in septic rats.

BACKGROUND: Coenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier in the mitochondrial respiratory chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to investigate the effects of CoQ10 on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. METHODS: Wistar rats were divided into Sham, CLP, Sham+CoQ10, CLP+CoQ10 subgroups. CoQ10 (10mg/kg/day) or vehicle (olive oil; 1mL/kg/day) was intraperitoneally injected for 15days. At 16th day, Sham or CLP operation was performed. 20h after the operations, MABF and phenylephrine responses of isolated aortic rings were measured. Tissue samples were obtained for histopathological and biochemical evaluations. Furthermore, survival rates were monitored throughout 96h. RESULTS: CoQ10 prevented mesenteric hypoperfusion and aortic dysfunction induced by CLP. Survival rate was %0 at 46th h in CLP group, but in CLP+CoQ10 group it was 37.5% at the end of 96h. CLP-induced elevations of serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were blocked by CoQ10. CoQ10 restored the increased liver, lung, spleen and kidney malondialdehyde levels and as well as reduced liver and spleen glutathione levels. The protective effects of CoQ10 on multiple organ damage were also observed histopathologically. CONCLUSIONS: CoQ10 showed protective effects in sepsis due to its preservative effects on mesenteric perfusion, aortic function and also its anti-inflammatory and antioxidative effects.

Thymoquinone protects against the sepsis induced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ damage in rats.

BACKGROUND: Thymoquinone (TQ) is a potent cytoprotective, antioxidant and anti-inflammatory agent. We aimed to investigate the possible protective effects of TQ on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in a murine sepsis model induced by cecal ligation and puncture (CLP). METHODS: Wistar rats were divided into the following four groups: Sham, CLP, Sham+TQ and CLP+TQ. TQ (1mg/kg/day) or vehicle (dimethyl sulfoxide, 1mL/kg/day) was intraperitoneally injected for 3 days. At 4th day Sham or CLP operation was applied. 20h after the operations, MABF and contractile responses of isolated aortic rings to phenylephrine were measured. Tissue samples were obtained for histopathological and biochemical examinations. Also, survival rates were recorded throughout 96h. RESULTS: TQ ameliorated mesenteric hypoperfusion and partially attenuated aortic dysfunction induced by CLP. Survival rate was %0 at 42nd h in CLP group, but in CLP+TQ group it was 33.4% at the end of 96h. Serum levels of AST, ALT, LDH, BUN, Cr and inflammatory cytokines (tumor necrosis factor-α, interleukin-1 ß and interleukin-6) increased in CLP group that were prevented by TQ. The decreases in liver, spleen and kidney glutathione levels and the increases in liver, lung, kidney and spleen malondialdehyde levels induced by CLP were inhibited by TQ. The histopathological protective effects of TQ on multiple organ damage due to CLP were also observed. CONCLUSION: TQ has ameliorative effects on sepsis due to its protective effects on mesenteric perfusion, contractile function of aorta and its anti-inflammatory and antioxidative effects.

Possible role of antioxidants and nitric oxide inhibitors against carbon monoxide poisoning: Having a clear conscience because of their potential benefits.

Carbon monoxide poisoning is one of the important emergency situations manifested by primarily acute and chronic anoxic central nervous system (CNS) injuries and other organ damages. Current descriptions and therapeutic approaches have been focused on the anoxic pathophysiology. However, this point of view incompletely explains some of the outcomes and needs to be investigated extensively. Considering this, we propose that reactive oxygen species (ROS) including especially nitric oxide (NO) are likely to be a key concept to understand the emergency related to CO poisoning and to discover new therapeutic modalities in CO toxicity. If we consider the hypothesis that ROS is involved greatly in acute and chronic toxic effects of CO on CNS and some other vital organs such as heart, it follows that the antioxidant and anti-NO therapies might give the clinicians more opportunities to prevent deep CNS injury. In support of this, we review the subject in essence and summarize clinical and experimental studies that support a key role of ROS in the explanation of pathophysiology of CO toxicity as well as new treatment modalities after CO poisoning.

The Role of ADAMTS1 and Versican in Human Myocardial Infarction: A Postmortem Study.

OBJECTIVE: To determine the role of a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) and fragmented versican in the myocardial infarction (MI) process in humans and to evaluate the diagnostic efficacy of ADAMTS1 for postmortem diagnosis of MI. METHODS: Thirty autopsied individuals were allocated into 2 groups, namely, a study group of individuals who died of myocardial infarction (n = 20), and a control group who died of trauma (n = 10). We performed standard immunohistochemical staining on myocardial tissue specimens, studying anti-ADAMTS1, anti-versican, and anti-versican C terminal peptide sequence (DPEAAE) fragments. RESULTS: Strong, diffuse staining was observed throughout myocardial tissue for ADAMTS1 in the 2 groups. However, in the study group, we observed no expression for ADAMTS1 around fibrotic areas but detected slight staining in coagulative and necrotic zones. CONCLUSION: Similar localizations of ADAMTS and fragmented versican in human heart tissue indicate that versican presumably is cleaved by ADAMTS1. Hence, ADAMTS1 can be regarded as a new marker for postmortem differential diagnosis of MI.

Role of ADAMTS5 in Unexplained Fetal Growth Restriction (FGR).

AIM: We aim to determine the role of serum and placental A disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS5) in fetal growth restriction (FGR). MATERIAL AND METHODS: 43 pregnancies suffering FGR and 45 healthy ones were homogenized for their body mass indices, ages, and gestational weeks. Expression of ADAMTS5 in placental samples was determined by immunohistochemical methods and concurrent maternal serum ADAMTS5 levels were determined with enzyme-linked immunosorbent assay. RESULTS: Expression of ADAMTS5 was higher in FGR group than the healthy control in placenta. Both the cytoplasmic staining pattern of the syncytiotrophoblasts and staining of the decidual plate were shown in the FGR group; but not in the control group. A negative correlation between serum ADAMTS5 levels and birth weight in FGR group was observed. CONCLUSION: Increased ADAMTS5 levels were observed in placental insufficiency cases. This study demonstrates that ADAMTS5 may be a sensitive indicator of placental insufficiency which has variable factors in etiology. Additional work is needed to delineate the mechanism of its involvement.

Idiopathic giant cell myocarditis in childhood: A case report.

Idiopathic giant cell myocarditis is a rare entity of unknown origin, which causes sudden death in more than half of the affected patients. It is rarely seen in childhood, and might result in death due to heart failure and ventricular arrhythmias. Idiopathic giant cell myocarditis is mostly diagnosed at autopsy incidentally. Here we present a rare case of childhood idiopathic giant cell myocarditis. A 10-year old boy found dead in his bed in the morning. Interview with family members revealed death the boy was in good health conditions apart from being overweight. At autopsy, external examination was completely normal. Internal examination revealed normal findings; the heart was 297g and macroscopically normal. No traces of any toxic agents detected in complete toxicological analyses. Areas characterized with granulomatous lesions, lymphocytes, histiocytes, and multinucleated giant cells were observed in myocardium at histopathological examination. No necrosis was observed in granulomatous areas. Tuberculosis was negative in the PCR assays. There were no signs indicative of fungal infection, and clinical status of the case was not compatible with the sarcoidosis. In this respect death was attributed to idiopathic giant cell myocarditis.

Idiopathic giant cell myocarditis in a newborn: case report.

Idiopathic giant cell myocarditis (IGCM) is a rare cause of arrhythmia, heart failure and death in children. The etiology of IGCM is unknown. Endomyocardial biopsy and histological examination are essential for diagnosis. In our case, a one-month-old baby boy with no prior medical history died during breast-feeding. The gross autopsy and drug screen failed to disclose a cause of death. Hemotoxylen Eosin (H&E) stained cardiac tissue slides showed widespread and multifocal necrosis accompanied by mixed inflammatory infiltrate. Admixed with the infiltrate were fibroblastic proliferation and multinucleated giant cells in the absence of sarcoid like granuloma. Although myocarditis is usually thought to be a disease of older children, infants can also be affected. This entity can be the cause of some cases of sudden unexpected death in infancy.

Evaluation of Vitality in the Experimental Hanging Model of Rats by Using Immunohistochemical IL-1ß Antibody Staining.

INTRODUCTION: Hanging is the most common suicide method in the world, and the discrimination of antemortem-postmortem hanging must be done at autopsy. The aim of this experimental study was to examine the immunohistochemical expression of IL-1ß antibody at the hanging mark skin samples of rats to discriminate antemortem and postmortem hangings. MATERIALS AND METHODS: A total of 20 Wistar albino rats were used for this study. The groups were as follows: A-1, antemortem control group; A-2, antemortem second-hour hanging mark skin samples; A-3, antemortem 24th-hour hanging mark skin samples; A-4, antemortem 72nd-hour hanging mark skin samples; B-1, postmortem control group; and B-2, postmortem second-hour hanging mark skin samples. Interleukin-1ß immunostaining was performed to all tissue samples. RESULTS: For epidermal cells, group A-1 samples did not show IL-1ß immunostaining, group A-2 samples were severely immunostained, and groups A-3 and A-4 samples' staining were slightly decreased. There was no IL-1ß antibody staining in groups B-1 and B-2 samples. For adnexal cells, groups A-1 and B-1 samples did not show IL-1ß immunostaining, staining of group A-2 samples was mild to severe, and groups A-3 and A-4 samples' staining were slightly decreased. Half of the group B-2 samples did not show IL-1ß immunostaining. For subepidermal cells, most of the samples of groups A-1 and B-1 showed slight immunostaining, groups A-2 and B-2 samples' staining were mild to severe, and there were slight immunostaining in groups A-3 and A-4 samples. The majority of vascular structure cells did not show IL-1ß immunostaining. CONCLUSION: Interleukin-1ß immunostaining of epidermal cells can discriminate antemortem-postmortem hangings, but vascular structure cells and subepidermal cells cannot discriminate vital hangings.

Acute generalized exanthematous pustulosis associated with tigecycline.

Acute generalized exanthematous pustulosis (AGEP) is a severe and rare eruption that develops mostly from factors related to drugs. It is characterized by a fever and a pustular eruption on the erythematous skin with an acute onset and without follicular localization. Etiopathogenesis has not yet been fully explained. Although it is similar to pustular psoriasis, its clinical, historical and histopathological characteristics are different. In this article, we present a case of AGEP associated with tigecycline that developed in a patient followed up in the intensive care unit for three months with an intra-abdominal injury after a trauma and Acinetobacter baumannii infection.

Fatal aorto-esophageal fistula in child: a case report.

Esophageal foreign body ingestion is especially frequent in childhood and may cause fatal complications in case of late diagnosis and delayed treatment. We present a case of 2-year old girl who was admitted to emergency department with massive bleeding. However, she died due to an unrecognized foreign body resulted an aorto-esophageal fistula. At autopsy an aorto-esophageal fistula was detected by gross examination. Tissue samples were obtained from the organs and fistula region. In histopathological examination, a calcified body with multinucleated giant cell and surrounding granulation tissue was detected at the bleeding site. An ulcerated fistula tract ran from the intima to the adventitia, passing through layers of esophageal wall was also noticed. The mortality rate for foreign body ingestion is less than 1%, except in cases of perforation. Therefore the presented case is among rare examples of fatal foreign body ingestions.

Respiratory epithelial adenomatoid hamartoma associated with inflammatory nasal polyposis: a case report.

Respiratory epithelial adenomatoid hamartoma (REAH) is an uncommon benign lesion of the nasal cavity and paranasal sinuses. The etiology is unclear, however it is considered to be secondary to chronic sinonasal inflammation. Although it is rare, REAH should be taken into consideration in differential diagnosis of the nasal lesions. Complete surgical excision of the lesion is generally enough for the cure. A detailed pathological examination is necessary to prevent unnecessary surgical interventions. In this article, we present a 60-year-old female patient with REAH in the left nasal cavity associated with inflammatory polyp in the right nasal cavity.

Basal cell adenocarcinoma of the minor salivary gland: a case report.

Basal cell adenocarcinoma (BCA) is an uncommon salivary gland neoplasm. The majority of salivary gland tumors are located in the parotid gland, while only a few involves the minor salivary gland of the oral cavity. Pathological diagnosis is important to differentiate BCA from other neoplasms, as the prognosis of the diseases is significantly different. In this article, we present a 41-year-old-male with BCA involving the upper labial mucosa.