St. Luke's Hospital

Gene expression silencing is one of the key tools in molecular biology and is widely applied in in vitro studies to investigate gene function and the mechanisms regulating cellular processes. The dynamic development of molecular techniques has resulted in the availability of numerous strategies that enable either transient or permanent reduction of gene activity at different stages of gene expression. The aim of this work is to review and compare gene expression silencing methods used in in vitro models, with particular emphasis on their mechanisms of action, efficiency, durability of the effect, and experimental limitations. The article discusses classical approaches based on RNA interference, including the use of siRNA, shRNA, and microRNA modulation, as well as strategies employing antisense oligonucleotides. Special attention is given to technologies based on the CRISPR system, including CRISPRi as a tool for reversible transcriptional repression and CRISPR–Cas9, which enables permanent disruption of gene function. Issues related to the delivery of molecular tools into cells, validation of silencing efficiency, and the importance of appropriate experimental controls are also addressed. Analysis of the literature indicates that the choice of an appropriate method should be tailored to the research objective, the characteristics of the gene under investigation, and the planned duration of the experiment. Increasingly, a complementary approach—combining different gene silencing strategies is recommended, as it enhances the reliability of results obtained in in vitro studies.

BackgroundChemotherapy-induced thrombocytopenia (CIT) is a common complication of chemotherapy that is associated with bleeding, reduced relative dose intensity, and potentially worse outcomes. No widely available therapies are approved for CIT.MethodsWe conducted a phase 3, international, double-blind, randomized, placebo-controlled trial involving patients with persistent CIT (platelet count, ≤85×109 per liter on trial day 1) who were receiving oxaliplatin-based multiagent cytotoxic chemotherapy for gastrointestinal cancers. Patients were randomly assigned in a 2:1 ratio to receive romiplostim or placebo for three chemotherapy cycles. The primary end point was the absence of CIT-induced modifications of the chemotherapy dose (reduction, delay, omission, or discontinuation) in both the second and third chemotherapy cycles.ResultsOf the 165 patients who underwent randomization (109 in the romiplostim group and 56 in the placebo group), 75% had colorectal cancer, 13% had gastroesophageal cancer, and 12% had pancreatic cancer; 72% of the patients in the romiplostim group and 61% of those in the placebo group had stage 4 disease. The percentage of patients with no CIT-induced modifications of the chemotherapy dose was 84% (92 of 109 patients) with romiplostim and 36% (20 of 56 patients) with placebo, which corresponded to an odds ratio of 10.16 (95% confidence interval [CI], 4.44 to 23.72; P<0.001) and a risk ratio of 2.77 (95% CI, 1.78 to 4.30; P<0.001). Adverse events of grade 3 or higher occurred in 37% of the patients who received romiplostim and in 22% of those who received placebo, which primarily reflected chemotherapy effects. Adverse events that were considered by the investigator to be related to romiplostim or placebo occurred in 12% of patients who received romiplostim and in 7% who received placebo, with the most frequent being nausea (2% in each group) and headache (2% in the romiplostim group); none were serious or led to death or discontinuation of romiplostim, placebo, or chemotherapy. Thromboembolic events occurred in 2% of patients who received romiplostim and in no patients who received placebo.ConclusionsIn this phase 3, placebo-controlled trial, romiplostim was efficacious in treating CIT. (Funded by Amgen and the Biomedical Advanced Research and Development Authority; RECITE ClinicalTrials.gov number, NCT03362177.)

Introduction: Serum creatinine (SCr) is the mainstay of kidney function assessment in the critically ill, but the serum concentration is affected by several non-kidney determinants not well accounted for in glomerular filtration rate estimation equations (eGFR). Cystatin C (cysC), an alternative kidney biomarker used for GFR estimation, may also be affected by non-kidney factors, including use of corticosteroids. Study purpose was to evaluate the impact of steroid exposure on cysC in acutely ill adults. Methods: This was a single-center, retrospective, observational cohort study at a large health system from 2011-2023 of acutely ill adults with at least two concurrent SCr and cysC pairs (i.e., tests drawn within 24-hours of each other) and exposure to systemic corticosteroids during hospitalization. Eligible patients had a SCr and cysC pair within 24 hours before steroid initiation and another pair within 72-hours after steroid initiation. Patients with acute kidney injury, need for kidney replacement therapy, kidney transplantation, pregnancy, incarceration, or refusal to authorize their records to be used for medical research were excluded. The primary outcome was change in cysC before and after steroid initiation. Descriptive statistics were used to compare the pre-steroid/post-steroid within group change in cysC to SCr. Results: 229 patients were included: mean ± SD age of 67 ± 16 years, 128 (55.9%) female. SCr and cysC were drawn median (IQR) 6.3 (3.2, 11.2) hours pre-steroid and 19.8 (13.5, 38.0) hours post-steroid. Steroid dose was 50 (25, 53) mg prednisone equivalents per day. Median cysC was 1.62 (1.20, 2.18) mg/L pre-steroid and 1.68 (1.20, 2.33) mg/L post-steroid, p=0.21. Median SCr was 1.10 (0.82, 1.40) mg/dL pre-steroid and 1.13 (0.80, 1.60) mg/dL post-steroid, p=0.089. Degree of difference in change from pre to post steroid was not clinically significant when cysC was compared to SCr (cysC change median 0.02 (IQR -0.17, 0.22) mg/L vs SCr change median 0.03 (IQR -0.11, 0.19) mg/dL; P = 0.035). Conclusions: Initiation of steroids in acutely ill patients did not significantly alter cysC concentrations in this large observational study. Findings suggest that routine doses of corticosteroids used in hospitalized patients are unlikely to significantly alter eGFR interpretation when based on cysC.

Introduction: Whiplash injuries are one of the most prevalent consequences of traffic collisions and are associated with a wide range of conditions referred to as whiplash-associated disorders (WAD). These manifestations are most commonly associated with pain and limited mobility of the cervical spine. A growing number of research indicates that these injuries may also impair the function of the temporomandibular joints (TMJs), thereby contributing to the development of their subsequent disorders. The aim of the study: The objective of the study was to discuss the correlations and dependency between whiplash injury and temporomandibular joint function. Acquiring this knowledge enables specialists to make precise diagnoses and implement appropriate therapeutic procedures, thereby reducing the risk of misdiagnosis or misdiagnosis omissions. Materials and methods: The following literature review provides a comprehensive discussion of the association between whiplash injuries and temporomandibular joint function. In December 2025, an extensive search of prominent electronic databases (PubMed, Google Scholar) was undertaken in order to identify relevant published studies on this subject. Conclusions: Studies indicate that whiplash injury may impair TMJ function and contribute to the development of TMJ disorders. The mechanisms underlying this relationship may be functional or neurophysiological in nature, but remain under investigation.Symptoms may be transient or persist long-term for several years, underscoring the necessity for a holistic diagnosis and an interdisciplinary therapeutic approach in patients after whiplash injury.

Introduction. Prostate biopsy remains the gold standard for the diagnosis of prostate cancer. In contemporary practice, increasing preference is given to fusion biopsy, which is more reliable and informative than conventional ultrasound‑guided systematic biopsy. Fusion prostate biopsy can be performed via transrectal or transperineal access, and the superiority of one approach over the other is still under investigation. Objective. To assess and compare the diagnostic performance of transrectal versus transperineal fusion prostate biopsy for the detection of prostate cancer. Materials &amp; methods. A comparative study was conducted between October 2024 and January 2025 at St. Luke’s Clinical Hospital, Saint Petersburg. A total of 162 men with suspected prostate cancer were enrolled. Group 1 comprised 115 patients who underwent transrectal fusion prostate biopsy. Group 2 included 47 patients who underwent transperineal fusion prostate biopsy using a stabilized technique with a stepper and stabilizer. Results. In the transrectal fusion biopsy group, prostate cancer was identified in 54 cases (46.95%) on targeted cores and in 81 cases (70.4%) on standard systematic cores. Systematic cores alone detected cancer in 44 patients (38.26%), whereas targeted cores alone did so in 5 patients (4.34%); in an additional 6 patients (5.22%), targeted cores upgraded the Gleason score. Omitting systematic sampling in transrectal fusion biopsy would have reduced overall cancer detection by 38.26%, including omission of clinically significant (aggressive) disease in 9.57% of cases. In the transperineal fusion biopsy group, cancer was detected in 31 patients (65.96%) on targeted cores and in 25 patients (53.19%) on systematic cores. Targeted cores alone identified cancer in 9 cases (19.15%), whereas systematic cores contributed only 3 additional cases (6.38%), all ISUP grade group 1. Targeted sampling led to Gleason score upgrading in 4 patients (8.51%). Conclusions. For the transperineal fusion technique, omitting systematic biopsies may reduce the number of cores without materially compromising diagnostic accuracy. In contrast, for transrectal fusion biopsy, systematic sampling remains crucial, particularly for detecting aggressive cancers and improving overall diagnostic yield. These approach‑specific differences warrant further investigation to refine diagnostic pathways for prostate cancer.