Balkan Medical Journal最新文献

Background: Since January 2015, the Cystic Fibrosis National Newborn Bloodspot Screening (CF-NBS) program has been implemented in Turkey with two samples of immune reactive trypsinogen (IRT-1/IRT-2) testing.

Aims: This study aimed to evaluate the Turkish national CF screening program, which included patients referred to a tertiary pediatric pulmonology center, to ascertain the optimal cut-off values for IRT-1/IRT-2 and to identify alternative strategies for mitigating the number of late-diagnosed false-negative patients (FNPs) who initially exhibited screen negative results but were diagnosed subsequently based on clinical suspicion. The study also compared NBS-positive patients to FNPs to determine the influence of delayed diagnosis.

Study design: A retrospective cohort study.

Methods: Screening for CF was conducted in accordance with the national CF-NBS program within 48-72 hours of birth by collecting a few drops of heel blood on Guthrie paper. A cut-off value of 90 μg/l was accepted for the first IRT, while 70 μg/l was accepted for the second sample. Infants with elevated IRT values in both samples were referred to the CF centers for a sweat test (ST). Based on the diagnosis, the NBS-positive infants referred to our CF center for ST analysis were divided into three groups: CF; cystic fibrosis-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID); and false-positive NBS. In addition, the study included NBS-negative patients who initially received negative screen results but were subsequently diagnosed with CF based on clinical suspicion.

Results: Of the 227 NBS-positive infants referred within the study period, 53 (23.34%) were diagnosed with CF (true-positive NBS), 11 were classified as CRMS/CFSPID (4.84%), and 163 were classified as falsepositive NBS (71.8%). CF was diagnosed in 66 infants, 53 (80.3%) of whom were confirmed using the NBS test, while the 13 (19.7%) patients who were missed on the NBS test were diagnosed based on clinical suspicion (FNP). The study findings indicate that the IRT/IRT approach exhibited a sensitivity of 80.3% and a positive predictive value (PPV) of 23.3%.

Conclusion: The current study is the first to analyze the NBS program for CF using data from the Western Anatolian Region of Türkiye. Due to the low sensitivity and PPV of the IRT/IRT protocol and the high proportion of false-positive infants and FNPs, the current national program is not practicable for Türkiye. False-negative results significantly delay the diagnosis and invalidate the screening objectives. It is essential to establish optimal cut-off values for IRT-1/IRT-2 or revise existing strategies to reduce the number of FNPs missed by the screening program.

In the recent years, there has been a burgeoning interest in Takotsubo syndrome (TTS), which is renowned as a specific form of reversible myocardial dysfunction. Despite the extensive literature available on TTS, clinicians still face several practical challenges associated with the diagnosis and management of this phenomenon. This potentially results in the underdiagnosis and improper management of TTS in clinical practice. The present paper, the first part (part-1) of the consensus report, aims to cover diagnostic and therapeutic challenges associated with TTS along with certain recommendations to combat these challenges.

Background: Albumin (ALB) and blood urea nitrogen (BUN) are both associated with the prognosis of acute ischemic stroke (AIS). A recent prognostic marker, the BUN/ALB ratio (BAR), has been suggested as a simple and sensitive method to predict certain acute diseases.

Aims: To determine the predictive value of BAR in relation to the risk of in-hospital mortality among AIS patients.

Study design: Retrospective cohort study.

Methods: Cox regression analysis was employed to assess the relationship between in-hospital mortality and BAR, with hazard ratios (HRs) and 95% confidence intervals. Subgroup analysis of acute pulmonary embolism, acute myocardial infarction (AMI), thrombolysis, thrombectomy, and septic shock was performed to further examine this relationship. The predictive value of BAR and BAR multivariate models for in-hospital mortality was evaluated and compared to BUN, ALB, the Acute Physiology and Chronic Health Evaluation IV (APACHE IV) score, and the Sequential Organ Failure Assessment Score (SOFA).

Results: Among the 1,635 eligible patients, 226 (13.81%) died during hospitalization. An elevated serum BAR level was associated with an increased in-hospital mortality risk (HR: 1.3) after covariates were adjusted. Additionally, this positive association was observed in patients without AP, AMI, thrombolysis, history of thrombectomy, or septic shock (all; p < 0.05). The efficacy of the BAR multivariate model in predicting in-hospital mortality among AIS patients was superior to that of both APACHE IV and SOFA, with an area under the curve of 0.87.

Conclusion: Serum BAR exhibits the potential to identify AIS patients with high mortality risk, which may contribute to enhanced disease surveillance and risk stratification.

Background: A high density of stromal tumor-infiltrating lymphocytes (sTILs) is positively correlated with the pathological complete response rate and favorable survival in patients with triple-negative breast cancer (TNBC). Heterogeneity in stromal lymphocyte distribution and limited tumor sampling may affect the accuracy of sTIL quantification in biopsy samples from patients receiving neoadjuvant therapy. Thus, identifying additional biomarkers to complement sTIL evaluation is essential.

Aims: To identify biomarkers that could be used to complement sTILs evaluation.

Study design: Retrospective cohort study.

Methods: A total of 162 patients with invasive TNBC were enrolled in the study. The following data were gathered: sTIL density, Ki67, nuclear grades of cancer cells, lymphovascular invasion status, the American Joint Committee on Cancer stage, axillary lymph node metastasis status, and ultrasonographic parameters of the tumor (size, shape, orientation, margin, internal echo pattern, posterior feature, and vascularity). The relationship between sTIL density and ultrasonographic or clinicopathological characteristics was investigated using both continuous and categorical analyses.

Results: Posterior features of the primary tumors was associated with sTIL density (p = 0.038). Additionally, the Ki67 levels and nuclear grades were also associated with sTIL density (p < 0.001 and p = 0.024, respectively). When stratified according to a 20% cut-off of sTIL density, the posterior features of primary tumors, Ki67 levels, and nuclear grades significantly differed between the high and low sTIL density tumors. Tumors with high Ki67 levels were more likely to exhibit high sTIL density than low sTIL density [odds ratio (OR): 2.75, p = 0.021]. Furthermore, nuclear grade III tumors demonstrated significantly higher sTIL density than nuclear grade I-II tumors (OR: 2.49, p = 0.014). Additionally, tumors with posterior enhancement or no posterior features were more likely to exhibit high sTIL density than tumors with acoustic shadows (OR: 2.91, p = 0.028; OR: 2.74, p = 0.022, respectively).

Conclusion: Low sTIL density is frequently observed in tumors exhibiting acoustic shadows on ultrasound. However, high sTIL density is more common in tumors with posterior enhancement or no posterior features. Furthermore, high Ki67 levels (> 40%) and high nuclear grades are positively correlated with high sTIL density. This study findings highlight the need for closer surveillance of these biomarkers to complement sTIL evaluation in TNBC.

Background: Fidgetin-like 1 (FIGNL1) is extensively overexpressed in a variety of cancers. It facilitates non‑small cell lung cancer tumor cell proliferation and hepatocellular carcinoma formation due to abnormal DNA repair. Clinically relevant data indicates that its high expression is linked with the poor prognosis of patients with renal clear-cell carcinoma, low-grade gliomas, and hepatocellular carcinoma. Nevertheless, the scope of FIGNL1’s involvement in cancer, particularly colorectal cancer (CRC), remains unclear.

Aims: To investigate the function of FIGNL1 in CRC.

Study design: Cell culture study.

Methods: The TCGA database and immunohistochemistry analysis were employed to investigate FIGNL1 expression in CRC tissue. A cell viability assay was performed using the Cell Counting Kit-8. The cell migration and invasion were evaluated using the transwell assay. Small interfering RNA (siRNA) transfection was conducted to knockdown FIGNL1 expression. Infection with FIGNL1 overexpression lentivirus was performed to promote FIGNL1 overexpression. The STRING database was employed for predicting protein interaction.

Results: FIGNL1 was substantially upregulated in human CRC tissues and was associated with TNM stages and lymph node metastasis in patients. The inhibition of CRC cell proliferation, migration, and invasion in Caco-2 cells was achieved by silencing FIGNL1 using siRNA. Additional investigations suggested that FIGNL1 overexpression could promote CRC cell proliferation, migration, and invasion via P38 signaling pathway activation in Colo-205 cells. Subsequent experiments demonstrated that FIGNL1-mediated P38 phosphorylation was contingent upon SPIDR interaction.

Conclusion: These results implied that FIGNL1 was a potential anticancer drug target, which also offered a novel strategy for future CRC treatment.

Takotsubo syndrome (TTS) still remains as an enigmatic phenomenon. In particular, long-term challenges (including clinical recurrence and persistent symptoms) and specific entities in the setting of TTS have been the evolving areas of interest. On the other hand, a significant gap still exists regarding the proper risk-stratification of this phenomenon in the short and long terms. The present paper, the second part (part-2) of the consensus report, aims to discuss less well-known aspects of TTS including specific entities, challenges after recovery and risk-stratification.