Advances in medical sciences最新文献

Purpose

The purpose was to explore the role of stereotactic body radiation therapy (SBRT) in providing local control (LC) for primary breast cancer in patients unable to undergo surgery.

Materials/methods

Between 2015 and 2019, 13 non-surgical candidates with 14 lesions were treated with SBRT for primary breast cancer. In 4 cases, SBRT was used after whole breast radiation therapy (WBRT; 40–50 Gy/20–25 fractions). SBRT dose was 30–40 ​Gy in 5 fractions for patients treated with SBRT alone and 25–32 ​Gy in 4–5 fractions for those treated with SBRT ​+ ​WBRT. LC and overall survival (OS) were estimated using Kaplan-Meier curves. Response was also assessed using RECIST guidelines.

Results

Median follow-up was 32 (range: 3.4–70.4) months. Imaging at median 2.2 (0.6–8.1) months post-SBRT showed median 43.2 ​% (range: 2–100 ​%) decrease in the largest diameter and median 68.7 ​% (range: 27.9–100 ​%) SUV reduction. There were 3 cases of local progression at 8.7–10.6 months. Estimated LC was 100 ​% at 6 months and 71.6 ​% at 12, 24 and 36 months.

Estimated median OS was 100 ​% at 6 months, 76.9 ​% at 12 months, and 61.5 ​% at 24 and 36 months. Acute toxicity (n ​= ​13; 92.9 ​%) included grade (G)1 (n ​= ​8), G2 (n ​= ​4), and G4 (necrosis; n ​= ​1). Late toxicity included G2 edema (n ​= ​1) and G4 necrosis (n ​= ​2, including 1 consequential late effect). Only patients treated with SBRT ​+ ​WBRT experienced acute/late G4 toxicity, managed with resection or steroids.

Conclusions

SBRT to primary breast cancer resulted in good LC in non-surgical/metastatic patients. Although necrosis (n ​= ​2) occurred in the SBRT ​+ ​WBRT group, it was successfully salvaged.

Uterine leiomyomas (ULs) are the most common benign smooth muscle cell steroid-dependent tumors that occur in women of reproductive age. Progesterone (P4) is a major hormone that promotes the ULs development and growth. P4 action in ULs is mediated mainly by its nuclear progesterone receptors (PGRs), although rapid non-genomic responses have also been observed. Data on the membrane progesterone receptors (mPRs) regulated signaling pathways in ULs in the available literature is still very limited. One of the essential characteristics of ULs is the excessive production of extracellular matrix (ECM). P4 has been shown to stimulate ECM production and collagen synthesis in ULs. Recent research demonstrated that, despite their benign nature, ULs may present with abnormal vasculature. P4 has been shown to regulate angiogenesis in ULs through the upregulation of vascular endothelial growth factor (VEGF) and by controlling the secretion of permeability factors. This review summarizes the key findings regarding the role of PGRs and mPRs in ULs, especially highlighting the potential ECM and angiogenesis modulation by P4. An increased understanding of this mechanistic role of nuclear and specifically mPRs in the biology of P4-modulated ECM and angiogenesis in the growth of ULs could turn out to be fundamental for developing effective targeted therapies for ULs.

Liver diseases of various etiologies are becoming increasingly common in the pediatric population. So far, the gold diagnostic standard in these disorders is liver biopsy. This procedure is invasive, painful and requires general anesthesia in this group of patients. Due to the continuous development of new research techniques, such as liver elastography, it is necessary to evaluate them in the context of their diagnostic usefulness. Ultrasound elastography, as a quick and effective method, is being used more and more often in the assessment and monitoring of liver dysfunction in both adults and children. There are several techniques of liver elastography, such as transient elastography, shear wave elastography consisting of various subtypes such as two-dimensional shear wave elastography, acoustic radiation force impulse and point shear wave elastography, which differ in terms of the measurement technique and the achieved results. The purpose of our review was to determine whether techniques of liver elastography could replace liver biopsy. Although now, based on the analyzed papers, elastography cannot replace liver biopsy, in our opinion, the role of this tool in monitoring pediatric patients with liver diseases will grow in the coming years.

Purpose

Bronchial hyperresponsiveness (BHR), a hallmark of bronchial asthma, is typically diagnosed through a methacholine inhalation test followed by spirometry, known as the methacholine challenge test (MCT). While spirometry relies on proper patients' cooperation and precise execution of forced breathing maneuvers, we conducted a comparative analysis with the portable nanomaterial-based sensing device, SenseGuard™, to non-intrusively assess tidal breathing parameters.

Materials and methods

In this prospective study, 37 adult participants with suspected asthma underwent sequential spirometry and SenseGuard™ measurements after inhaling increasing methacholine doses.

Results

Among the 37 participants, 18 were MCT responders, 17 were non-responders and 2 were excluded due to uninterpretable data. The MCT responders exhibited a significant lung function difference when comparing the change from baseline to maximum response. This was evident through a notable decrease in forced expiratory volume in 1 ​s (FEV₁) levels in spirometry, as well as in prominent changes in tidal breathing parameters as assessed by SenseGuard™, including the expiratory pause time (T_rest) to total breath time (T_tot) ratio, and the expiratory time (T_ex) to T_tot ratio. Notably, the ratios T_rest/T_tot (∗p ​= ​0.02), T_ex/T_tot (∗p ​= ​0.002), and inspiratory time (T_in) to T_ex (∗p ​= ​0.04) identified MCT responders distinctly, corresponding to spirometry (∗p ​< ​0.0001).

Conclusions

This study demonstrates that tidal breathing assessment using SenseGuard™ device reliably detects clinically relevant changes of respiratory parameter during the MCT. It effectively distinguishes between responders and non-responders, with strong agreement to conventional spirometry-measured FEV₁. This technology holds promise for monitoring clinical respiratory changes in bronchial asthma patients pending further studies.

Purpose

Urine output (UO) is an important intraoperative parameter that is not yet electronically monitored. We compared an automatic urinometer (AU) based on a smart scale with a manual urinometer (MU).

Patients and methods

This prospective study investigated the hourly UO of 35 preoperative patients with an indwelling urinary catheter using AU, MU, and cylinder measurements. Data were analyzed using the Bland-Altman method. A questionnaire related to the use of the AU was completed by medical staff (n=25).

Results

Compared to the cylinder measurements, the differences in measurements by the AU and the MU were −6.31 ​± ​15.03 ​mL/h (p=0.018) and 20.26 ​± ​26.81 ​mL/h (p=0.001), respectively. The r values for the comparison of cylinder measurements with AU and MU values were 0.985 (p<0.001) and 0.968 (p<0.001), respectively. Bland-Altman analyses showed that cylinder measurements had better agreement with the AU measurements than with the MU measurements. Also, the medical staff reported that the use of the AU was easier to learn than the use of the MU (p<0.001).

Conclusions

Compared to the MU values, AU values were noninferior; they had significantly less bias and temporal deviation. Additionally, the medical staff reported that the use of the AU was easier to learn than the use of the MU.

Purpose

Serum creatinine may be an objective biomarker of salient health issues in adults with cerebral palsy (CP). The objective was to assess the age-related association between serum creatinine with 3-year risk of cardiorespiratory morbidity/mortality and fracture among adults with CP.

Patients and methods

This retrospective cohort study used medical records between Jan. 1, 2012 and Oct. 2, 2022 from adults ≥18 years old with CP. The association between baseline serum creatinine with the 3-year risk of all-cause mortality, respiratory/cardiovascular morbidity/mortality, and fracture was assessed by age and sex using logistic regression. The discriminative ability of serum creatinine alone and in conjunction with other variables was assessed.

Results

Over the 3-year follow-up, 8.3% of 1368 adults with CP had all-cause mortality, 25.6% had respiratory morbidity/mortality, 12.4% had cardiovascular morbidity/mortality, and 8.9% sustained a fracture. The association between serum creatinine with outcomes was dependent on age. For younger adults, lower creatinine had a higher odds ratio (OR) for all-cause mortality, respiratory morbidity/mortality, and fracture. For 51–60 year olds, higher creatinine had a higher OR for cardiovascular morbidity/mortality. Serum creatinine alone had modest prediction of outcomes, and generally improved prediction when added to models that included sex and co-occurring intellectual disabilities and epilepsy (c-statistic range, 0.54–0.84).

Conclusions

Lower serum creatinine may reflect frailty while higher levels may reflect kidney dysfunction, helping to explain the differential associations by age. Serum creatinine may be a useful biomarker as part of risk prediction models for these salient health issues for adults with CP.

In this review, we have summarized the existing knowledge of ulcerative colitis (UC) markers based on current literature, specifically, the roles of potential new biomarkers, such as circulating, fecal, genetic, and epigenetic alterations, in UC onset, disease activity, and in therapy response. UC is a complex multifactorial inflammatory disease. There are many invasive and non-invasive diagnostic methods in UC, including several laboratory markers which are employed in diagnosis and disease assessment; however, colonoscopy remains the most widely used method. Common laboratory abnormalities currently used in the clinical practice include inflammation-induced alterations, serum autoantibodies, and antibodies against bacterial antigens. Other new serum and fecal biomarkers are supportive in diagnosis and monitoring disease activity and therapy response; and potential salivary markers are currently being evaluated as well. Several UC-related genetic and epigenetic alterations are implied in its pathogenesis and therapeutic response. Moreover, the use of artificial intelligence in the integration of laboratory biomarkers and big data could potentially be useful in clinical translation and precision medicine in UC management.

Recent events have raised concerns about the outbreak of a pandemic by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An infection caused by a virus can provoke an inflammatory reaction, which can result in severe lung damage, failure of several organs, and death. The unique genetic makeup of each individual may be a component in the development of each of these responses. In this context, genetic variants of the genes linked to the invasion of the virus into the host's body can be analyzed. Various elements have a function in viral entry. ACE2 is used by SARS-CoV-2 as a receptor to enter the cell. TMPRSS2 is then responsible for cutting the virus into its components. In addition, lung damage occurs when there is an imbalance between ACE1 and ACE2. Another component that plays a significant role in virus penetration is called IFITM3, which is created as a reaction to interferon. This protein prevents viruses in the Coronaviridae family from entering cells.

This study aimed to analyze DNA polymorphisms in the ACE2, ACE1, TMPRSS2, and IFITM3 genes. Findings showed certain polymorphisms appear to be associated with the severity of the disease, including respiratory, coronary, and neurological disorders. The results also indicated that certain polymorphisms were protective against this virus. Varying populations have a different frequency of high-risk polymorphisms, so different treatment and preventative techniques must be implemented. Additional population studies should be conducted in this region to reduce the incidence of COVID-19-related morbidity and mortality.

Purpose

Myeloproliferative neoplasms (MPN) are a heterogeneous group of hematopoietic stem-cell diseases with excessive proliferation of one or more blood cell lines. In this study, we evaluated the effect of different oxygen concentrations on HIF-1α and NOS3 gene expression to determine the effect of the bone marrow microenvironment on JAK2V617F positive Philadelphia chromosome negative (Ph⁻) MPNs.

Patients and methods

Peripheral blood mononuclear cells (MNC) of 12 patients with Ph⁻ MPN were collected. The presence of JAK2V617F allele status was determined with allele-specific nested PCR analysis. MPN CD34⁺ and CD34^depleted populations were isolated from MNC by magnetic beads. Separate cell cultures of CD34^+/depleted populations were managed at different oxygen concentrations including anoxia (∼0%), hypoxia (∼3%), and normoxia (∼20%) conditions for 24 ​h. HIF-1α and NOS3 gene expression changes were examined in each population related to JAK2V617F status with real time RT-PCR.

Result

It was revealed that relative HIF-1α and NOS3 expressions were significantly increased in response to decreased oxygen concentration in all samples. Relative HIF-1α and NOS3 expressions were found to be higher especially in CD34⁺ and CD34^depleted populations carrying JAK2V617F mutations compared to MPN patients carrying wild-type JAK2.

Conclusion

JAK2V617F might have specific role in HIF-1α and NOS3 regulations with respect to low oxygen concentrations in Ph⁻ MPN. Further evaluations might reveal the effect of JAK2V617F on Ph⁻ MPN pathogenesis in bone marrow microenvironment.

Purpose

This study aimed to evaluate the role of Translationally Controlled Tumor Protein (TCTP) in breast cancer (BC) and investigate the effects of sertraline, a serotonin selective reuptake inhibitor (SSRI), on BC cells. The objective was to assess the potential of sertraline as a therapeutic agent in BC treatment by examining its ability to inhibit TCTP expression and exert antitumor effects.

Material and Methods

We utilized five different BC cell lines representing the molecular heterogeneity and distinct subtypes of BC, including luminal, normal-like, HER2-positive, and triple-negative BC. These subtypes play a crucial role in determining clinical treatment strategies and prognosis.

Results

The highest levels of TCTP were observed in triple-negative BC cell lines, known for their aggressive behavior. Sertraline treatment reduced TCTP expression in BC cell lines, significantly impacting cell viability, clonogenicity, and migration. Additionally, sertraline sensitized triple-negative BC cell lines to cytotoxic chemotherapeutic drugs (doxorubicin and cisplatin) suggesting its potential as an adjunctive therapy to enhance the chemotherapeutic response. Bioinformatic analysis of TCTP mRNA levels in TCGA BC data revealed a negative correlation between TCTP levels and patient survival, as well as between TCTP/tpt1 and Ki67. These findings contradict our data and previous studies indicating a correlation between TCTP protein levels and aggressiveness and poor prognosis in BC.

Conclusions

Sertraline shows a promise as a potential therapeutic option for BC, particularly in triple-negative BC. Its ability to inhibit TCTP expression, enhance chemotherapeutic response, highlights its potential clinical utility in BC treatment, specifically in triple-negative BC subtype.