Pancreatic ductal adenocarcinoma: exploring clinicopathological trends and racial disparities in a comprehensive U.S. population-based study.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy about 50% of PDAC are metastatic at presentation. In this study, we evaluated PDAC demographics, annual trend analysis, racial disparities, survival rate, and the role of different treatment modalities in localized and metastatic disease. METHODS: A total of 144,824 cases of PDAC were obtained from the SEER database from 2000 to 2018. RESULTS: The median age was 69 years, with a slightly higher incidence in males (52%) and 80% of all cases were white. Among cases with available data, 43% were grade III tumors and 57% were metastatic. The most common site of metastasis was the liver (15.7%). The annual incidence has increased steadily from 2000 to 2018. The overall observed (OS) 5-year survival rate was 4.4% (95% CI 4.3-4.6%), and 5 years cause-specific survival (CSS) was 5% (95% CI 5.1-5.4%). The 5-year survival with multimodal therapy (chemotherapy, surgery, and radiation) was 22% (95% CI 20.5-22.8%). 5-year CSS for the blacks was lower at 4.7% (95% CI 4.2-5.1%) compared to the whites at 5.3% (95% CI 5.1-5.4%). Multivariate analysis found male gender and black race associated with worse prognosis. Kaplan-Meier survival analysis found multimodal therapy to have the best outcomes in all three stages. CONCLUSION: PDAC is an aggressive malignancy with male gender and black race are associated with a poor prognosis. Surgery with chemoradiation was associated with the best overall survival. With steadily increasing rates of PDAC, improved treatment modalities are paramount to improving survival in these patients.

Vertical stratification and seasonality of fecal indicator bacteria in New York City playground sandboxes.

Sandboxes in public play spaces afford a crucial opportunity for urban children to engage in naturalistic play that fosters development of cognitive, social, and motor skills. As open pits, sandboxes in New York City public playgrounds are potentially exposed to fecal inputs from various sources, including wild and domestic animals. A longitudinal study of thirteen sandboxes located in public playgrounds on the east side of Manhattan reveals ubiquity of the fecal indicator bacteria enterococci and Escherichia coli through all seasons. The highest concentrations of bacteria occur in surface sand (n = 42; mean enterococci 230 MPN/g and E. coli 182 MPN/g dry weight), with significantly lower levels at depths below the surface (n = 35; mean enterococci 21 MPN/g and E. coli 12 MPN/g dry weight), a stratification consistent with fecal loading at the surface. Generalized linear mixed models indicate that sand depth (surface vs. underlayers) is the most influential variable affecting bacterial levels (P <0.001 for both enterococci and E. coli), followed by sampling season (P <0.001 for both). Bacterial concentrations do not vary significantly as a function of playground location or ZIP code within the study area. Children's exposure while playing in sandboxes likely reaches 105 enterococci and 104E. coli in a typical play period. Microbial source tracking to identify fecal hosts reveals dog, bird, and human biomarkers in low concentrations. Open sandbox microcosms installed at ground level in the urban environment of Manhattan are fouled by enterococci and E. coli within two weeks, while adjacent closed microcosms exhibit no fecal contamination over a 33-day sampling period. Collectively, our results indicate that increasing the frequency of sand refills and covering sandboxes during times of disuse would be straightforward management strategies to mitigate fecal contamination in playground sandboxes.

Pancreatic Diffuse Large B-cell Lymphoma in the US Population.

BACKGROUND: Pancreatic lymphomas (PLs) represent <2% of all lymphomas and <0.5% of all pancreatic neoplasms. An accurate histologic diagnosis of PL is needed to predict prognosis and adequately treat the patient. This study aims to investigate the demographic, clinical, and pathological factors affecting the prognosis and survival of pancreatic diffuse large B-cell lymphoma (DLBCL). METHODS: Demographic and clinical data from 493 cases of DLBCL of the pancreas were identified between 2000 and 2018 using the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: The most common age group was between the ages of 70 and 79 years (27.0%). While 44% of cases involved distant sites (a proxy for secondary pancreatic DLBCL), regional and localized involvement was seen in 33%, with the most common cause of death being a primary pancreatic DLBCL. Most patients (71%) received only chemotherapy (systemic therapy). The overall five-year observed survival was 46% (95% CI, 43.5-48.3). The one-year and five-year survival with chemotherapy only was 68% (95% CI, 65.3-70.3) and 48% (95% CI, 44.7-50.5), respectively. The one-year and five-year survival with surgery and chemotherapy was 96% (95% CI, 91.3-99.9) and 80% (95% CI, 71.4-89.2), respectively. Surgery with chemotherapy (HR: 0.397 (95% CI, 0.197-0.803), p = 0.010) were both positive predictors in survival prognosis. Multivariable analysis identified age >55 years (HR: 2.475 (95% CI, 1.770-3.461), p < 0.001), distant stage (HR: 6.894 (95% CI, 4.121-11.535), p < 0.001), and undergoing no surgery (HR: 2.610 (95% CI, 1.307-5.215), p = 0.007) as negative predictors for survival. CONCLUSION: PLs are rare malignant pancreatic neoplasms with DLBCL being the most common histological subtype. An accurate and timely diagnosis of pancreatic DLBCL is necessary to implement effective treatments and reduce mortality. Systemic therapy (chemotherapy) with or without surgical therapy improved survival. Increased age and regional and distant spread negatively impacted survival.

Pulmonary large cell neuroendocrine carcinoma (LCNEC): a population-based study addressing recent molecular-genetic advances and emerging therapeutic approaches.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare, aggressive cancer most commonly found in the lungs but not exclusively, with a worse prognosis than non-small cell lung carcinomas. Currently, LCNEC patients are treated using small cell and non-small cell protocols. This study aims to use the SEER database to identify demographic, clinical, pathological, and therapeutic factors affecting the prognosis and survival of patients with LCNEC of the lung. METHODS: Demographic, clinical, and management data of patients with lung LCNEC were extracted from the SEER database for the period 2000-2018. RESULTS: In the USA, LCNEC has a higher incidence in elderly white men: M:F ratio = 1.2:1, Caucasian: 83.3%, mean age: 67 ± 10.2 years. The most common treatment modality was chemotherapy only: 29.2%, followed by surgery: 21.5% (but in this group the statuses of chemotherapy were unknown), and combination surgery/chemotherapy: 8.8%. The overall and cause-specific 5-year survival was 17.5% (95% CI 16.3-18.8) and 21.9% (95% CI 20.5-23.4), respectively. By treatment, the best 5-year survival was for surgery alone (48%), followed by multimodality therapy (chemo + surgery + radiation) at 35% (95% CI 27-43). Age > 60 years, male gender, size > 7 cm, and nodal and liver metastasis were independent risk factors associated with increased mortality. CONCLUSION: Lung LCNEC is an aggressive neoplasm most common in older white males that presents at an advanced stage despite small primary tumors. Most patients die within 2 years. The best predictor of survival is surgery with chemotherapy. Given its dismal prognosis, new treatment guidelines are needed for this aggressive cancer.

Effect of CCR2 Knockout on Tendon Biomechanical Properties in a Mouse Model of Delayed Rotator Cuff Repair.

BACKGROUND: The high incidence of incomplete or failed healing after rotator cuff repair (RCR) has led to an increased focus on the biologic factors that affect tendon-to-bone healing. Inflammation plays a critical role in the initial tendon-healing response. C-C chemokine receptor type 2 (CCR2) is a chemokine receptor linked to the recruitment of monocytes in early inflammatory stages and is associated with an increase in pro-inflammatory macrophages. The purpose of this study was to evaluate the role of CCR2 in tendon healing following RCR in C57BL/6J wildtype (WT) and CCR2-/- knockout (CCR2KO) mice in a delayed RCR model. METHODS: Fifty-two 12-week-old, male mice were allocated to 2 groups (WT and CCR2KO). All mice underwent unilateral supraspinatus tendon (SST) detachment at the initial surgical procedure, followed by a delayed repair 2 weeks later. The primary outcome measure was biomechanical testing. Secondary measures included histology, gene expression analysis, flow cytometry, and gait analysis. RESULTS: The mean load-to-failure was 1.64 ± 0.41 N in the WT group and 2.50 ± 0.42 N in the CCR2KO group (p = 0.030). The mean stiffness was 1.43 ± 0.66 N/mm in the WT group and 3.00 ± 0.95 N/mm in the CCR2KO group (p = 0.008). Transcriptional profiling demonstrated 7 differentially expressed genes (DEGs) when comparing the CCR2KO and WT groups (p < 0.05) and significant differences in Type-I and Type-II interferon pathway scores (p < 0.01). Flow cytometry demonstrated significant differences between groups for the percentage of macrophages present (8.1% for the WT group compared with 5.8% for the CCR2KO group; p = 0.035). Gait analysis demonstrated no significant differences between groups. CONCLUSIONS: CCR2KO may potentially improve tendon biomechanical properties by decreasing macrophage infiltration and/or by suppressing inflammatory mediator pathways in the setting of delayed RCR. CLINICAL RELEVANCE: CCR2 may be a promising target for novel therapeutics that aim to decrease failure rates following RCR.

A Rare Case of Giant Cell Arteritis After the Administration of Checkpoint Inhibitor Therapy in a Metastatic Renal Cell Carcinoma Patient.

We present a rare case of metastatic renal cell carcinoma in a patient who developed giant cell arteritis (GCA) after the administration of checkpoint inhibitor therapy with nivolumab and ipilimumab. The patient was initially treated with a combination of nivolumab and ipilimumab, showing a near-complete response with minimal side effects. However, after several cycles of checkpoint inhibitor therapy, the patient developed symptoms consistent with GCA, leading to a halt in the immunotherapy. This report highlights the complexity of managing the adverse effects of immunotherapeutic agents and the importance of a multidisciplinary approach in the management of complications such as GCA.

Papillary Renal Cell Carcinoma: Demographics, Survival Analysis, Racial Disparities, and Genomic Landscape.

Papillary renal cell carcinoma (PRCC) is the second most common histological subtype of renal cell cancer. This research aims to present a large database study highlighting the demographic, clinical, and pathological factors, racial disparities, prognosis, and survival of PRCC. The clinical and demographic data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and molecular data was cured from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. PRCC had a median age of diagnosis at 64 years, with a higher incidence in men (77%), and Whites (68%). 70.3% of cases were Grades I-IV (13, 53, 31, and 3%, respectively). In patients with known data, 85% were localized to the kidney, and 84% of cases were 7 cm in size. No metastasis occurred in 97% of the known data. The most common treatment offered was surgical resection (9%). The 5-year overall survival was 79%, with patients undergoing surgery having a 90.6% 5-year survival. Multivariable analysis revealed age > 60 years, Black race, poor histologic differentiation, distant metastases, and tumor size > 10 cm as independent risk factors for mortality. The most common mutations identified from the COSMIC database were MET, KMT2D, KMT2C, ARID1A, and SPEN. PRCC affects male individuals in the sixth decade of life. Increased age, Black race, distant metastases, and tumors > 10 cm are associated with a worse prognosis. Surgical resection offers a favorable survival outcome. Next-generation sequencing (NGS) could identify potentially targetable alterations and future personalized therapeutic approaches.

Role of Serum Homocysteine and Outcome in Patients With Traumatic Brain Injury.

Background There have been indications of a correlation between serum homocysteine (Hcy) levels and poor patient outcomes in traumatic brain injury (TBI). Thus, we aimed to explore the role of serum Hcy in influencing the outcome post TBI. Methods A case-control study was conducted at Liaquat University of Medical and Health Sciences (LUMHS) between January 15, 2022 and July 1, 2022. All patients between the ages of 18 and 75 years who presented with TBI, irrespective of severity, were included in the study. All patients with neurological disorders and infections, including but not limited to cerebral tuberculosis, Alzheimer's disease, epilepsy, brain cancer, Parkinson's, and stroke, were excluded from the study. For comparison, healthy controls with similar demographics were enrolled in the study. All patients and controls underwent biochemical evaluation of serum Hcy and neurological assessment at presentation. In addition, all sociodemographic and clinical parameters, including the Glasgow Outcome Score (GOS), were collected in a predefined pro forma. Results A total of 175 patients were included who had experienced TBIs, along with an equal number of healthy controls. The most common etiology was road traffic accidents in 82 (46.9%) patients. The mean Glasgow Coma Score (GCS) at presentation was 5.78 ± 1.72. The mean Hcy levels were 31.4 ± 7.97 µmol/L in TBI patients and 11.12 ± 5.87 µmol/L in the control healthy patients (p=0.001). It was found that the severity of hyperhomocysteinemia (HHcy) was significantly related to the worst outcome possible, i.e., death (p=0.001). Conclusion The study concluded that patients who had suffered from a TBI had significantly higher serum Hcy levels. Furthermore, the study highlighted that the patients with the worst outcomes had more severe hyperhomocysteinemia (HHcy) than those with better outcomes. Moreover, patients with low GOS scores were more likely to have HHcy.

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies?

Programmed death-ligand (PD-L) 1 and 2 are ligands of programmed cell death 1 (PD-1) receptor. They are members of the B7/CD28 ligand-receptor family and the most investigated inhibitory immune checkpoints at present. PD-L1 is the main effector in PD-1-reliant immunosuppression, as the PD-1/PD-L pathway is a key regulator for T-cell activation. Activation of T-cells warrants the upregulation of PD-1 and production of cytokines which also upregulate PD-L1 expression, creating a positive feedback mechanism that has an important role in the prevention of tissue destruction and development of autoimmunity. In the context of inadequate immune response, the prolonged antigen stimulation leads to chronic PD-1 upregulation and T-cell exhaustion. In lung cancer patients, PD-L1 expression levels have been of special interest since patients with non-small cell lung cancer (NSCLC) demonstrate higher levels of expression and tend to respond more favorably to the evolving PD-1 and PD-L1 inhibitors. The Food and Drug Administration (FDA) has approved the PD-1 inhibitor, pembrolizumab, alone as front-line single-agent therapy instead of chemotherapy in patients with NSCLC and PD-L1 ≥1% expression and chemoimmunotherapy regimens are available for lower stage disease. The National Comprehensive Cancer Network (NCCN) guidelines also delineate treatment by low and high expression of PD-L1 in NSCLC. Thus, studying PD-L1 overexpression levels in the different histological subtypes of lung cancer can affect our approach to treating these patients. There is an evolving role of immunotherapy in the other sub-types of lung cancer, especially small cell lung cancer (SCLC). In addition, within the NSCLC category, squamous cell carcinomas and non-G12C KRAS mutant NSCLC have no specific targetable therapies to date. Therefore, assessment of the PD-L1 expression level among these subtypes of lung cancer is required, since lung cancer is one of the few malignances wherein PD-L1 expression levels is so crucial in determining the role of immunotherapy. In this study, we compared PD-L1 expression in lung cancer according to the histological subtype of the tumor.

Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study.

A subset of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis develop debilitating knee stiffness (reduced range of motion) for poorly understood reasons. Dysregulated inflammatory and immune responses to surgery correlate with reduced surgical outcomes, but the dysregulated gene signatures in patients with stiffness after TKA are poorly defined. As a consequence, we are limited in our ability to identify patients at risk of developing poor surgical outcomes and develop preventative approaches. In this pilot study we aimed to identify perioperative blood gene signatures in patients undergoing TKA for knee osteoarthritis and its association with early surgical outcomes, specifically knee range of motion. To do this, we integrated clinical outcomes collected at 6 weeks after surgery with transcriptomics analyses in blood samples collected immediately before surgery and at 24 h after surgery. We found that patients with stiffness at 6 weeks after surgery have a more variable and attenuated circulating gene expression response immediately after surgery. Our results suggest that patients with stiffness following TKA may have distinct gene expression signatures detectable in peripheral blood in the immediate postoperative period.

Mucoepidermoid Carcinoma of the Salivary Gland: Demographics and Comparative Analysis in U.S. Children and Adults with Future Perspective of Management.

Background: Salivary gland neoplasms are uncommon in both pediatric and adult populations. Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland tumors and usually presents with atypical clinical features. This study sought to evaluate the demographic and clinical factors affecting outcomes in adults and pediatric populations with MEC that could be used to risk stratification for treatment selection and clinical trial enrollment. Methods: Data on 4507 MEC patients were extracted from the Surveillance Epidemiology and End Result (SEER) database (2000−2018). Patients aged ≤ 18 years were classified into the pediatric population, and those older than 18 years were placed in the adult group. Kaplan−Meier survival curves were created to analyze survival probabilities for various independent factors. Results: The pediatric population comprised 3.7% of the entire cohort, with a predominance of females (51.5%), while the adult population constituted 96.3% of the cohort, with a predominance of female patients (52.2%). Caucasians were the predominant race overall (75.3%), while more African Americans were seen in the pediatric group. In tumor size of <2 cm overall, poorly differentiated tumors with higher metastasis rates were observed more in adults (11.3% and 9.3%) than in the pediatric population (3.0% and 4.8%, p < 0.05). Surgical resection was the most common treatment option (53.9%), making up 63.6% of the pediatric and 53.5% of the adult groups. A combination of surgical resection and radiation was used in 29.8% of the entire cohort while a combination of surgical resection, radiation, and chemotherapy made up only 3.2%. The pediatric group had a lower overall mortality rate (5.5%) than the adult group (28.6%). Females had a higher 5-year survival rate in comparison to males (86.5%, and 73.7%, respectively). Surgical resection led to a more prolonged overall survival and 5-year cancer-specific survival (98.4% (C.I, 93.7−99.6) in the pediatric group and 88.8% (C.I, 87.5−90.0) in the adult group), respectively. Metastasis to the lung, bone, brain, and/or liver was found to have significantly lower survival rates. Multivariate analysis demonstrated that adults (hazard ratio [HR] = 7.4), Asian or Pacific Islander (HR = 0.5), male (HR = 0.8), poorly differentiated histology (HR = 3.8), undifferentiated histology (HR = 4.5), regional spread (HR = 2.1), and distant spread (HR = 3.2) were associated with increased mortality (p < 0.05). Conclusions: Mucoepidermoid carcinoma of the salivary glands primarily affects Whites and is more aggressive in adults than in the pediatric population. Even with surgical resection, the overall survival is poor in the adult population as compared to its pediatric counterparts. Advanced age, larger tumor size, male sex, and lymph node invasion are associated with increased mortality.

Prevalence of Thyroid Dysfunction in Patients With Hepatitis C.

INTRODUCTION: Hepatitis C has been linked to a multitude of autoimmune disorders, including rheumatoid arthritis, thyroid disease, cryoglobulinemia, immune thrombocytopenic purpura, systemic lupus erythematosus, and Sjögren's syndrome. In this study, efforts were made to draw a parallel between hepatitis C and thyroid dysfunction. METHODS: This case-control study was conducted between June 2020 and March 2021 in the gastroenterology ward of a tertiary care hospital. We enrolled 300 hepatitis C-positive patients in this study through consecutive convenient non-probability sampling. In addition, 300 patients without hepatitis C were signed up as a control group. Blood sampling for thyroid function tests was conducted via phlebotomy from the cubital vein and the samples were dispatched to the laboratory for further study. RESULTS: The control group had more euthyroid patients as compared to patients with hepatitis C (74.6% vs. 89.6%; p-value: <0.01). Hepatitis C patients had more cases of primary hypothyroidism compared to the control group (10.6% vs. 4.6%; p-value: 0.005). Similarly, patients with hepatitis C had a higher prevalence of subclinical hypothyroidism compared to the control group (6.0% vs. 1.3%; p-value: 0.002). CONCLUSION: Hepatitis C patients have a high frequency of thyroid dysfunction, particularly primary hypothyroidism and subclinical hypothyroidism. Therefore, it is important to ensure regular screening for early prognosis and avoid treatment modalities that are known to cause thyroid abnormalities.