The American journal of the medical sciences最新文献

Hypercalcemia has rarely been associated with seminomas. Due to the limited data available, the pathophysiology of hypercalcemia in seminoma has not been established in literature. We present a case of a 59-year-old male who presented with weakness, abdominal fullness, fatigue, constipation, and a 14 lb unintentional weight loss. On initial presentation he was found to be hypercalcemia with calcium of 16.2 mg/dL (normal 8.6-10.3 mg/dL). Subsequently, a metastatic seminoma was discovered with no evidence of bony metastasis. 1,25-dihydroxyvitamin D was elevated at >200 pg/mL (reference 19.9-79.3 pg/mL). PTH was suppressed at 11 pg/mL (reference 12-88 pg/mL). PTHrP was normal at 1.0 pmol/L (reference ≤4.2 pmol/L), 25‑hydroxy vitamin D was low at 22.6 ng/mL (reference 30-100 ng/mL), and phosphorus was normal at 3.9 mg/dL (reference 2.4-4.9 mg/dL). These findings indicate 1,25-dihydroxyvitamin D mediated hypercalcemia of malignancy. Hypercalcemia in seminoma has been reported in 11 cases, that we review in this report. However, few cases present sufficient data to conclude the pathophysiology of hypercalcemia. In all four cases that presented 1,25-hydroxyvitamin D levels, the levels were elevated, suggesting seminomas are associated with 1,25-hydroxyvitamin D mediated hypercalcemia. Interestingly, one case was associated with increased 1,25-hydroxyvitamin D and increased PTHrP levels, suggesting there may be multiple mechanisms of hypercalcemia in seminomas.

Background: Sepsis is a critical condition with a significant risk of mortality. Advanced age is one factor in increasing mortality in intensive care.

Objectives: The aim of this study is to investigate the association between mean heart rate (MHR) and 30-day mortality among older patients with sepsis in the intensive care unit (ICU).

Methods: All older patients (age 65 or older) with sepsis for first time in ICU admission in Medical Information Mart for Intensive Care-IV (MIMIC-IV) were included in this retrospective study. The effect of MHR within 24 h of ICU admission on 30-day mortality was assessed according to multivariable Cox regression models, restricted cubic splines and two-piecewise Cox regression models.

Results: The total number of participants was 6598 (mean heart rate, 83.8 ± 14.3 bpm). A total of 1295 (19.6%) patients died within 30 days after ICU admission. MHR within 24 h of admission was associated with 30-day mortality (J-shaped association) in older patients with sepsis in the ICU, with an inflection point at about 74 bpm and a minimal risk observed at 73 to 82 bpm of MHR.

Conclusions: In this retrospective cohort study, there was a J-shaped association between MHR and 30-day mortality in older patients with sepsis admitted to the ICU and a minimal risk observed at 73 to 82 bpm of MHR. If further confirmed, this association may provide a theoretical basis for formulating the target strategy of heart rate therapy for these patients.

Background: Resistance to chemotherapy containing cisplatin (DDP) is a main challenge in the treatment of triple-negative breast cancer (TNBC). Forkhead box O4 (FOXO4) is frequently downregulated in DDP-resistant cells. However, it is unclear whether FOXO4 down-regulation is related to DDP resistance. Here, we investigated the relationship between FOXO4 and DDP resistance in TNBC.

Methods: We established the DDP-resistant cell lines MDA-MB-231/DDP and BT-549/DDP through in vitro selection. CCK-8 and colony formation assays analyzed cell growth. The resistance index was calculated. Cell autophagy was evaluated. Western blotting and qRT-PCR measured protein and gene expression. The binding between FOXO4 and TGF-β1 was determined by the dual-luciferase reporter assay.

Results: FOXO4 expression was significantly lower in MDA-MB-231/DDP and BT-549/DDP cells. FOXO4 overexpression increased the sensitivity of TNBC cells to DDP. The PI3K class Ⅲ and Beclin-1 levels and LC3-II/LC3-I ratio elevated significantly in DDP-resistant cells. Moreover, the autophagic flux was enhanced in DDP-resistant cells. 3-MA enhanced the sensitivity of TNBC cells to DDP by inhibiting autophagy. Overexpression of FOXO4, treatment with 3-MA, and their combination significantly reduced the drug resistance index. FOXO4 directly targeted TGF-β1. Additionally, TGF-β1 knockdown inhibited autophagy and restored the sensitivity of DDP-resistant cells to DDP. Mechanistically, FOXO4 affected TNBC resistance to DDP by regulating autophagy and TGF-β1.

Conclusion: FOXO4 overexpression, in combination with autophagy inhibitors, can significantly improve the sensitivity of TNBC-resistant cells to DDP. These findings reveal the role and mechanism of FOXO4 in DDP sensitivity and may provide evidence for the development of TNBC therapies.

Background: This study aims to explore racial disparities in immediate outcomes of Transjugular Intrahepatic Portosystemic Shunt (TIPS) among Native Americans, a group that have higher prevalence of liver cirrhosis but were the "invisible group" in previous TIPS studies due to their small population size.

Methods: The study identified Native Americans and Caucasians who underwent TIPS in National/Nationwide Inpatient Sample (NIS) database from Q4 2015-2020. Preoperative factors, including demographics, indications for TIPS, comorbidities, etiologies for liver disease, primary payer status, and hospital characteristics, were matched by 1:5 propensity score matching. In-hospital post-TIPS outcomes were then compared between the two cohorts.

Results: There were 6,658 patients who underwent TIPS, where 101 (1.52%) were Native Americans and 4,574 (68.70%) were Caucasians. Native Americans presented as younger, with a lower socioeconomic status, and displayed higher rates of alcohol abuse and related liver diseases. After propensity-score matching, Native Americans had comparable in-hospital post-TIPS outcomes including mortality (8.33% vs 9.09%, p = 1.00), hepatic encephalopathy (18.75% vs 25.84%, p = 0.19), acute kidney injury (28.13% vs 30.62%, p = 0.71), and other adverse events. Native Americans also had similar wait from admission to operation (2.15 ± 0.30 vs 2.87 ± 0.21 days, p = 0.13), hospital length of stay (7.43 ± 0.63 vs 8.62 ± 0.47 days, p = 0.13), and total costs (158,299 ± 14,218.2 vs 169,425 ± 8,600.7 dollars, p = 0.50).

Conclusion: Native Americans had similar immediate outcomes after TIPS compared to their propensity-matched Caucasians. While these results underscore effective healthcare delivery of TIPS to Native Americans, it is imperative to pursue further research for long-term post-procedure outcomes.

Background: The association between serological indexes and occurrence of complications in patients with autoimmune gastritis (AIG) remains unclear.

Methods: 91 patients with AIG were recruited and their clinical information were collected. The differences between serological indexes and complications of AIG were analyzed. And potential biomarker for early prediction and diagnosis of AIG with complications was explored.

Results: AIG patients in our study was 58.12 ± 11.68 years old, containing 31 males and 60 females. G17 was elevated in 49 of 52; PGI/II decreased in 43/49; GPA positive in 48/61; Anemia presented 28 in 80; Vitamin B12 deficiency occurred 23 in 58. Neuroendocrine tumor (NET) was the most common complication in AIG patients, accounting for 27/91. The second was polyps, making up for 14/91. There is also 9/91 of gastric mucosa neoplasia happened in AIG. No significant difference of G7, PGI, PGII, PGI/II and VB12 in AIG was found in different gastric mucosal lesions (P > 0.05). However, AIG patients with TPOAb positive had a higher risk in the occurrence of NET simultaneously (P = 0.0212). Those AIG with NET patients exhibited a significantly higher TPOAb level (P = 0.0078). ROC curve suggested that TPOAb can predict the existence of NET in AIG (AUC = 0.7410, P < 0.05).

Conclusion: We found that TPOAb can serve as a predictive biomarker of NET in AIG. This accessible test is helpful for endoscopy specialists to pay attention to gastric mucosal lesions in TPOAb-positive AIG patients, improving early diagnosis and intervention of comorbidities ability.

Objective: To explore the ideas and research progress in diagnosing and treating hypercalcemic crisis in patients with cancer.

Methods: We reviewed the clinical data, diagnosis and treatment of hypercalcemic crisis in a patient with mixed glandular neuroendocrine carcinoma of the endometrium.

Results: The patient had gastrointestinal symptoms and acute renal impairment as the main manifestations, and the blood biochemical indexes suggested a hypercalcemic crisis with elevated parathyroid hormone (PTH). No lesions were seen in the parathyroid glands on imaging and nuclide imaging, but an abnormal pelvic mass was seen in the pelvis and the biopsy of the uterine cervix tissue suggested that it was an adenocarcinoma. Surgery was performed to remove the mass, and postoperative findings suggested endometrial large-cell neuroendocrine carcinoma with endometrioid adenocarcinoma. The calcium and PTH decreased to normal after surgery and chemotherapy.

Conclusions: The condition of the hypercalcemia crisis is dangerous, so it is necessary to think from different aspects of the clinical diagnosis and treatment.

A 53-year-old man with acute myeloid leukemia received an allogeneic hematopoietic cell transplant (HCT) from a matched unrelated donor. One month after his transplantation, he developed ARDS requiring initiation of VV-ECMO. He suffered from pancytopenia, managed with frequent transfusions, granulocyte-colony stimulating factor (G-CSF) and weekly thrombopoietin receptor agonist. On ECMO day 17, the patient developed severe hypotension after insertion of a chest tube for a large right-sided pneumothorax. CT angiography of the abdomen showed hemoperitoneum. Exploratory laparotomy revealed approximately 4 L of blood and a ruptured splenic hilum. A splenectomy was performed. Unfortunately, the patient continued to require multiple daily blood products and his condition continued to decline despite two reoperations. His family chose to discontinue ECMO and he passed away peacefully. Spontaneous splenic rupture after GM-CSF has never been reported in patients on VV-ECMO. This manuscript reviews the literature regarding the pathophysiology and clinical manifestation of this rare occurrence.

Background: Reduced effective circulating blood volume and impaired peripheral tissue perfusion play an important role in the pathophysiology of shock. However, there have been no studies examining the relationship between Doppler ultrasound of the superior mesenteric artery (SMA) under different shock conditions.

Methods: We evaluated a total of 85 patients, including 63 patients with different types of shock and 22 in the control group. we included patients who were diagnosed with shock upon admission or developed shock during their hospital stay. At the same time, patients with stable hemodynamics, no use of vasoactive drugs and normal lactate levels were used as a control group. We collected SMA Doppler ultrasound parameters, including Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), Resistance Index (RI), pulsatility index (PI), Time-Averaged Mean Velocity (TAMV), and Blood Flow (BF).

Results: In the cardiac shock group, SMA PSV, TAMV, and BF were lower compared to the other groups. There was no significant difference in SMA RI and PI between the different types of shock groups, but both were significantly lower than the control group. Cardiac index (CI) is correlated with SMA PSV (r = 0.487, P = 0.000) and TAMV (r = 0.538, P = 0.000), whereas SVRI is not correlated with SMA RI and PI. Lactate levels was correlation with SMA RI (r = -0.307, P = 0.000) and PI (r = -0.287, P = 0.000). The area under the ROC curve of SMA RI and PI to predict hyperlactatemia was 0.85[0.78-0.91] and 0.83[0.76-0.90].

Conclusions: The velocity parameters of SMA Doppler ultrasound such as TAMV and PSV can reflect cardiac function. The measurements of SMA RI and PI are correlated with lactate levels, having a positive predictive value for hyperlactatemia and provide guidance for fluid resuscitation in patients with shock in the future.

Background: Early detection of carotid plaque (CP) can help reduce the burden of ASCVD in the general population. CP and triglyceride-glucose index (TyGi) are associated with insulin resistance.

Objectives: We performed a meta-analysis exploring the association of TyGi levels with the incidence of CP.

Methods: A systematic search of PubMed, Scopus, and Google Scholar till September 2023 reporting TyGi and CP identified 67 studies, of which 13 met our study criteria. TyGi was assessed both categorically and continuously. Binary random-effects models used for pooled odds ratios (OR) with 95 % confidence intervals (CI) and I² statistic for heterogeneity.

Results: Analyzed data from 163,792 patients with a mean age of 53 ± 8.9 years, primarily female (51.5 %). Common comorbidities were hypertension (42.4 %) followed by dyslipidemia (24.3 %). Multivariable analysis showed that high vs. low TyGi quartile was associated with a higher risk of CP with unadjusted OR (1.82, 95 % CI [1.5 - 2.21], p < 0.01; I² = 95.77, p < 0.01) and adjusted OR (1.3, 95 % CI [1.16 - 1.46], p < 0.01; I² = 79.71, p < 0.01). Increasing TyGi also had a higher risk of CP with unadjusted OR (1.53, 95 % CI [1.15 - 2.03], p < 0.01; I² = 98.48, p < 0.01) and adjusted OR (1.23, 95 % CI [1.11 - 1.35], p < 0.01; I² = 89.82, p < 0.01). The association was validated by sensitivity analysis.

Conclusion: Our study indicates a higher risk of CP in patients with higher TyGi scores, underscoring its significance as a predictor for carotid atherosclerosis.