Journal of Investigative Medicine最新文献

Autoimmune thyroid disorders (AITD) are the most common autoimmune human disorders as the thyroid gland is a main target for autoimmunity. The association between rheumatologic and thyroid disorders has long been known, the most common being the association with rheumatoid arthritis. Our study was conducted to screen for the presence of symptoms, signs, and immune markers suggesting the presence of Sjogren's syndrome among patients with autoimmune thyroid disorders. Eighty AITD patients (46 patients with Hashimoto's thyroiditis and 34 patients with Graves' disease) were included in the study and 40 healthy subjects matched age and sex as a control group. The two groups were compared according to 2002 the American-European Consensus Group (AECG) criteria for diagnosis of primary Sjogren's syndrome. 12.5% of AITD patients (n = 10 patients) were diagnosed with Sjogren's syndrome (AITD-SS). Eight out of ten of AITD-SS had Hashimoto's disease while only two had Grave's disease. Anti-Ro was detected in serum of seven patients of the AITD patients with Sjogren syndrome while anti-La was detected in serum of eight patients. The most independent predictors of Sjogren's syndrome in AITD patients are anti-La, ESR, and salivary gland sonographic change. Sjogren's syndrome has been found in patients with AITD, and also patients with AITD have symptoms that mimic sicca disease despite not fulfilling the criteria for diagnosis.

Immunotherapy with checkpoint inhibitors has improved the outcomes of patients with metastatic lung cancer in recent years. Despite improved prognosis, not all patients respond to treatment. Therapeutic interventions to build on the success of immune checkpoint inhibitors are needed. A retrospective review of patient records for patients who had received immune checkpoint inhibitors in a single cancer center over 4 years was undertaken. Demographic and disease characteristics of patients with metastatic non-small cell lung cancer were recorded. Data on other treatments including chemotherapy and radiation therapy were extracted, and survival outcomes were calculated. Most (81.8%) of the 77 metastatic lung cancer patients examined had received palliative radiation therapy within 3 months of starting immune checkpoint inhibitors. While the survival outcomes of these patients did not differ from patients who had not received radiotherapy, patients who had undergone hypofractionated radiotherapy (defined as one or more fractions of 700 cGy or higher) displayed a better overall survival (OS) than the rest of the cohort. Palliative radiation therapy administered in proximity with immune checkpoint inhibitors immunotherapy had no effect on the OS of metastatic lung cancer patients. However, patients receiving palliative radiotherapy with fractions above 700 cGy showed better OS. Further studies are needed to optimize a combination strategy.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there have been nearly seven million deaths associated with COVID-19 and over thirteen billion total vaccine doses administered worldwide. This study aimed to evaluate the patient demographics and laboratory values that might help predict individuals at risk of having a deep vein thrombosis (DVT) formation while hospitalized with COVID-19. Focusing on the four major strains alongside the associated vaccination availability periods in the United States to devise risk stratification and management algorithms. This retrospective cohort study analyzed 4429 COVID-19-positive patients admitted to a single, tertiary care institution from March 2020 to February 2024 who underwent venous duplex ultrasound due to clinical suspicion. It was found that active chemotherapy treatment, higher weight (77.0 vs 84.0 kg), and longer LOS to first duplex (5 vs 10 days) were independent predictors of mortality. In addition, men, older age (68 vs 70 years old), medical history of DVTs, and longer LOS to first duplex (5 vs 8 days) were prognostic for DVT formation. More importantly, the prevalence of DVT was not statistically different between each COVID-19 wave, despite diminished mortality and morbidity over time. This study also demonstrated many non-predictive variables including COVID-19 as the principal diagnosis, BMI, smoking status, history of atrial fibrillation, stroke, CAD, vaccination status, and traditional laboratory values. Helping establish a critical foundation to analyze trends of anticoagulant and systemic corticosteroid use in this COVID-19 patient population.

To investigate the impact of vaccines on sociodemographic characteristics, clinical profiles, and outcomes of SARS-CoV-2 infection among healthcare workers in South China during the period of Omicron variant dominance, a retrospective, analytical cross-sectional study was conducted. The findings revealed that while full vaccination could not prevent Omicron variant infection efficiently (26.51% uninfected vs 14.29% uninfected between vaccinated and unvaccinated participants, p = 0.506), it did substantially reduce the length of viral clearance significantly (p < 0.05), potentially facilitating quicker patient recovery. Unvaccination was found to be an independent risk factor for slow clearance when a linear regression analysis model was used (Coefficient: -3.516; 95% CI: -6.425 to -0.607; p = 0.020). Therefore, all eligible individuals should be fully vaccinated to get prepared for a potential wave of epidemic in the future.

Extrapulmonary tuberculosis (EPTB) is an important public health problem due to its diverse clinical presentations, diagnostic complexities, and significant impact on patient outcomes and public health. Our study aimed to understand the sociodemographic, clinical, and laboratory characteristics as well as diagnostic and treatment modalities of adult patients with EPTB. This is a multicentric retrospective study that covers patients with EPTB cases followed up from January 2015 to December 2022 among tuberculosis (TB) dispensaries and Infectious Diseases and Clinical Microbiology clinics of 15 hospitals located in various regions of Turkey. The study included 64.6% women with a mean age of 44 years and a mortality rate of 3.5% within 1 year of diagnosis. Initial constitutional symptoms were predominantly fatigue (57%) and anorexia (53.7%). The most commonly affected sites were the lymph nodes (49.1%) and pleura (9.7%). The lumbar region was particularly involved in cases with spinal TB. Diagnostic findings included acid-fast bacilli positivity in 27.5% of cases, tuberculosis polymerase chain reaction positivity in 41%, elevated adenosine deaminase levels in 91.2% (especially in pleural and peritoneal fluids), and mycobacterial culture positivity in 40.9%. Pathology slides showed granulomatous inflammation in 97.7%. Increased C-reactive protein (CRP) levels correlated with the number of organs affected. Anti-TB treatment-related hepatotoxicity was detected in 8.9% of patients. In this study, it is important to note that the lumbar region is predominantly affected with involvement in spinal region. CRP level was consistent with the number of organ involvements and was one of the most critical results of this study.

Early onset colorectal cancer (EO-CRC) is increasing. We investigated the risk factors for ER-CRC compared to late onset colorectal cancer (LO-CRC). CRC patients between the years 1999 and 2021 were retrospectively evaluated. Data regarding demographics, comorbidities, malignancies, and mortality were collected. Data were retrieved using the MdClone platform from a large Health Maintenance Organization. The cohort was subdivided into EO-CRC (age ≤ 50 years) and LO-CRC (age ≥ 51 years) groups. 61,679 patients diagnosed with CRC were included in our analysis, 30,456 (49.4%) males, and 4891 (7.9%) Arabs, with an average age at diagnosis of 70.1 ± 13.1 years. 5561 (9%) patients were included in the EO-CRC group. Over the last decades, higher rates of EO-CRC were diagnosed compared to the previous decade, 9.8% vs 8.3%, p < 0.001. A higher percentage of EO-CRC patients were females (52.8% vs 50.4%), had a family history of CRC (9.9% vs 5.5%), were Arabs (18.7% vs 6.9%), and were smokers (32.7% vs 30.2%) compared to LO-CRC patients. Significantly lower rates of comorbidities such as ischemic heart disease, diabetes mellitus, hypertension, obesity, and iron deficiency anemia were found among EO-CRC patients, with a lower all-cause mortality (27.7% vs 63.1%, p < 0.001). 348 (6.3%) of the EO-CRC patients had another Lynch-related cancer until age 50 years compared to 45 (0.1%) at the LO-CRC. Young individuals with increased risk for CRC need special consideration and should be referred early for screening and endoscopic investigation, particularly those with a family history of CRC, smokers, and those of Arab ethnicity.

Hyperglycemia, one of the major risk factors for atherosclerosis, leads to the accumulation of advanced glycation end products (AGEs), contributing to cardiovascular complications. Such accumulation may accelerate the progression of vascular disease in patients with diabetes. Reverse cholesterol transport (RCT) protein, ATP-binding membrane cassette transporters A1 and G1 (ABCA1 and ABCG1) and cholesterol 27-hydroxylase facilitate cholesterol removal from macrophages. AGE inhibits RCT by reducing the expression of ABCA1 and ABCG1. This study aimed to evaluate whether plasma from poorly controlled adolescents with type 1 diabetes (T1D) disrupts cholesterol homeostasis in human monocytes/macrophages. Twenty healthy controls (HCs) and 20 patients with type 1 diabetes mellitus (T1DM), 10-19 years old, were enrolled. Naïve THP-1 macrophages were exposed to plasma from each HC and patient with T1D. Following incubation, mRNA for cholesterol efflux (ABCA1, ABCG1, and 27-hydroxylase) and cholesterol uptake (CD36, ScR-A1, lectin oxidized low-density lipoprotein (LOX)-1, and CXCL16) were isolated. Foam cell formation was quantified to confirm the pro-atherogenic effects of T1D plasma on macrophages. Results showed that T1D plasma had an elevated level of N-(carboxymethyl)-lysine-modified proteins and upregulated CXCL16 and, to a lesser degree, ScR-A1. This change in gene expression in the presence of T1D plasma is associated with increased lipid accumulation and foam cell formation by THP-1 macrophages. In our study, these cells' uptake of an AGE product occurred mainly through the SR-A1 and CXCL16 receptors, leading to increased intracellular oxidized low-density lipoprotein. We conclude that AGEs may contribute to accelerated atherosclerosis in diabetes through effects on both forward and reverse cholesterol movement.

Endocrine disruptive chemicals (EDCs) are considered as the potential attributes for the increasing trend in obesity and metabolic syndrome (MS) through disruption of sex hormones, particularly in women. We evaluated the association of understudied EDC compounds with total testosterone (TT), sex hormone-binding globulin (SHBG), obesity, and MS. A population-based cross-sectional study was conducted using the National Health and Nutrition Examination Survey datasets collected during the years 2013-2016. Women of age ≥15 years with urinary measurements of nonpersistent EDCs, including bisphenol, triclosan, triclocarban, dichlorophenol, and paraben compounds were included in this study. Data were analyzed using the modified Poisson models to estimate the adjusted relative risk (RR) and 95% confidence interval (CI). The associations were also validated by considering TT and SHBG concentrations as the outcomes. The study included 1974 women with 11% high TT, 10.5% low SHBG, 40% obesity, and 46.2% MS. A medium to high exposure to bisphenol-A (RR = 1.64; 95% CI: 1.14, 2.35, p = 0.009), bisphenol-F (RR = 1.83; 95% CI: 1.35, 2.49, p < 0.001), bisphenol-S (RR = 1.83; 95% CI: 1.35, 2.49, p = 0.041) and 2, 4- dichlorophenol (RR = 1.61; 95% CI: 1.06, 2.45, p = 0.026) were associated with low SHBG but not with high TT. In addition, high exposure to triclosan was also inversely associated with SHBG concentrations (regression coefficient = -0.09; 95% CI: -0.15, -0.02, p = 0.013). However, these EDCs were found to be associated with SHBG, obesity, and MS according to menopausal status. High exposure to certain nonpersistent EDCs was associated with low SHBG, obesity, and MS according to menopausal status.

Triple-positive breast cancer (TPBC) is a type of breast cancer that overexpresses estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Dysregulation of ER signaling has been implicated in the pathogenesis of breast cancer. ERα activation triggers the production of second messengers, including cAMP, leading to the activation of signals such as PI3K/AKT or Ras/MAPK. Ruxolitinib is a specific inhibitor of JAK1/JAK2. MK-2206 is an allosteric inhibitor of the Akt. The limitations of the use of ruxolitinib and MK-2206 as single agents necessitate the development of combination therapies with other drugs. This study is the first to investigate the effects of combining ruxolitinib with MK-2206 on MAPK and PI3K/AKT signaling in BT474 breast cancer cells. In addition, this work aimed to increase the anticancer effects of cotreatment with MK-2206 and ruxolitinib. Ruxolitinib, MK-2206, and their combination reduced cell viability in a dose- and time-dependent manner, as determined by MTT assays after 48 h of treatment. Colony formation and wound healing assays demonstrated that MK-2206 exhibited a synergistic anti-proliferative effect. The effects of ruxolitinib, MK-2206, and their combination on PI3K/AKT and MAPK signaling were assessed via western blotting. Ruxolitinib and MK-2206 combined treatment inhibit cell death in BT474 cells by downregulating ERα, Src-1, ERK1/2, SAPK/JNK, and c-Jun. Our results revealed the relationships among the ERα, PI3K/AKT, and MAPK signaling pathways in ER+ breast cancer cells. Understanding the interactions among ERα, PI3K-AKT-mTOR, and MAPK could lead to novel combination therapies.

While some studies have suggested better outcomes for critically ill patients with balanced solutions over normal saline, the best type of intravenous fluid to use for stroke patients remains unknown. Using a retrospective chart review of 2015-2019 Get with the Guidelines^® data at a single academic medical center, this study sought to determine whether balanced solutions or normal saline are associated with risk of hemorrhagic transformation or 90-day disability in patients with acute ischemic stroke treated with intravenous thrombolysis. Exposure was the type of intravenous fluid and outcomes were modified Rankin scale (mRS) ≤2 at 90 days and hemorrhagic transformation. Multivariate analysis controlled for age, demographics, medical history, time to tissue plasminogen activator (tPA), and admission stroke scale. We identified 302 patients who received thrombolysis, of which 166 patients had mRS data at 90 days. In univariate analysis, exposure to any balanced solution was associated with increased 90-day disability (odds ratio (OR) 4.3, 95% confidence interval (CI) 3.8-4.9) and hemorrhagic transformation (OR 2.0, 95% CI 1.3-2.2). In multivariate analysis, exposure to a balanced solution at any time was associated with increased 90-day disability (OR 6.3, 95% CI 2.4-17.0, p < 0.01), but not hemorrhagic transformation. Thus, this observational trial demonstrated that exposure to balanced solutions is associated with an increased risk of disability at 90 days and possibly hemorrhagic transformation in patients with acute ischemic stroke treated with intravenous thrombolysis. This data would suggest that normal saline is a preferred solution in these patients, though larger future trials are needed.