Valentin Titus Grigorean

Endogenous retroviruses (ERVs), LINE-1 elements, and other endogenously active transposable-element families are now being studied for their role as a potential interface between epigenetic control and innate immunity. Here, we discuss how locus-specific failures in repressive complexes containing ATRX–DAXX–H3.3 and TRIM28–SETDB1–H3K9me3 may allow these elements to enter into unique molecular states that include double-stranded RNA, DNA/RNA hybrid molecules, RNA–protein complexes, reverse-transcription products, and RNA. Each of these states differs from the others in terms of its persistence, structural characteristics, and accessibility to sensors such as MDA5, RIG-I, cGAS–STING, and ZBP1, as well as host restriction pathways. We also emphasize that simply expressing a retroelement does not imply that it is competent to bind to a sensor and/or undergo productive retrotransposition. Rather, a distinction needs to be made between intermediate stages in the process of retrotransposition and productive retrotransposition itself. Therefore, the evidence needed to assign a specific sensor to a particular retroelement product must be presented. Furthermore, persistent stress caused by retroelement activity could converge with multiple cellular processes, such as p53–CDKN1A/p21-mediated cell-cycle arrest, PML-mediated nuclear organization, and lysosomal or metabolism-based changes leading to long-lived microglial states; however, demonstrating path dependence after removing the initiating perturbation would be required to demonstrate true hysteresis. Finally, downstream activation of complement pathways could have effects on synaptic function via separate CR3-dependent, trafficking-based, and contact-regulatory mechanisms. Overall, we recommend a locus-specific, structure-specific, and time-course-resolved approach for determining how the various states of endogenously active retroelements cross the genome–immunity boundary and contribute to neuroinflammatory dysfunction.

Aim: Aging together with the wide range of diseases causing death are ones of the influential factors of cardiac wall remodeling regarding both their structural and functional features. The authors compared the changes of myocardial interstitial capillary network density (vascular density – VD) between the main regions of the cardiac wall during patients’ ageing and depending on patients’ cause of death. Patients, Materials and Methods: Five cross-sections from epicardium to endocardium [left ventricle wall (LVW): anterior segment (LV_AW), lateral segment (LV_LW), and posterior segment (LV_PW); interventricular septum (IVS); and right ventricle wall (RVW)] were collected during necropsies from 95 patients died with different ages (AP_01, 0–24 years; AP_02, 25–44 years; AP_03, 45–64 years; and AP_04, >64 years) and with different types of causes of death (V_P – vascular diseases, NV_P – non-vascular diseases, and S/V_Dth – suspect/violent cause of death, considered also control group – CG) in the hospital. Tissue samples were processed classically and immunomarked with anti-cluster of differentiation 34 (CD34) antibody. Glass slides were transformed into virtual slides. The VD was determined with a dedicated built program. Mean values (AVs) were compared with Pearson’s correlation test. Results: On one hand, VD increased slowly from youth to elderly in LV_Ws and decreased with age in the IVS and RVW. It had the lowest values in LV_Ws till AP_03 and in RVW in elderly. The highest values were in RVW till 44 years and then in IVS. VD had higher values in women than in men along the main regions of the cardiac wall and a divergent behavior, with age, in the two sexes. Thus, in men, VD had an increasing trend with age from LV_AW to RVW [correlation matrix (CM) positive, p-value >0.05] whereas in women, the trend was decreasing with age from LV_AW to RVW (CM negative, p-value >0.05), excepting IVS where it increases (CM positive). On the other hand, the VD had lowest values in V_P group and highest values in CG in general and in both sexes. Its values increased from LVW to RVW in V_P group and CG and decreased in NV_P group in general and in both sexes. They also increased from LV_AW toward LV_PW in all groups of COD and in both sexes. The VD AVs were higher in females than in males in CG and NV_P group and higher in males than in females in V_P group. Its values were lowest in both sexes in V_P group but highest in men in NV_P group and in women in CG. Conclusions: VD and is remodeling with aging in different ways both along the cardiac wall’s regions and in the two sexes, being generally higher in females than in males. The causing death diseases determine different pathways of interstitial capillary network remodeling both along the different regions of the cardiac wall and in the two sexes, the most important being the capillary density decrease in vascular diseases as compared with all other causes of death.

Background/Objectives: Quality of life (QoL) and functional recovery are essential outcomes in patients undergoing rectal cancer surgery. In addition to oncological results, bowel dysfunction and stoma-related issues may significantly affect postoperative well-being. We aimed to evaluate QoL changes at 1 and 6 months postoperatively and functional outcomes in rectal cancer patients who underwent curative surgical treatment, sphincter-preserving surgeries (SPS) or abdominoperineal resection (APR). Owing to its impact on QoL, several functions were assessed using the Low Anterior Resection Syndrome (LARS) score. Methods: This retrospective observational study consisted of 99 patients who underwent curative rectal cancer surgery, of which 38 patients had colostomy, and 61 no colostomy. To assess patient-reported outcomes related to QoL, the EORTC QLQ-C30 questionnaire, QLQ-CR29 questionnaire, and LARS instrument were sent to the patients at 1 and 6 months postoperatively. Changes over time were analyzed using paired statistical tests, and subgroup analyses were performed according to colostomy status and surgical approach. Results: Significant improvements were observed in the global health status and all major functional domains between 1 and 6 months postoperatively. The global health status increased from 74.9% to 86.5% (p < 0.001). Symptom burden decreased significantly, particularly for fatigue (−18.31), pain (−14.48), diarrhea (−12.46), and insomnia (−11.45), representing clinically meaningful improvements. Patients who underwent abdominoperineal resection or resection with colostomy had lower QoL scores at 1 month but showed substantial improvement at 6 months, becoming comparable to those who underwent SPS. LARS outcomes demonstrated progressive functional recovery, with the proportion of patients without LARS increasing from 39 to 46, while major LARS decreased from 7 to 3 patients. However, approximately 40% of patients in the SPS group continued to report moderate-to-severe LARS symptoms. Conclusions: In this study, QoL and bowel function improved significantly during the first 6 months after colorectal cancer surgery. Although most patients demonstrated recovery, persistent bowel dysfunction and stoma-related challenges remain important issues. These findings highlight the need for comprehensive postoperative care and routine assessment of both QoL and functional outcomes.

Tumor budding (TB), defined as isolated single cells or small clusters of up to four tumor cells at the invasive front of colorectal carcinoma (CRC), is recognized as an important histopathologic marker associated with adverse tumor behavior. This review summarizes current knowledge on the morphologic assessment, biological significance, and clinical relevance of TB, emphasizing emerging artificial intelligence (AI) methods that aim to automate and standardize its quantification. Standardized reporting by the International Tumor Budding Consensus Conference (ITBCC) has improved reproducibility, while novel deep-learning algorithms demonstrate potential for objective and prognostically relevant TB assessment. Integration of AI-based TB evaluation with molecular and stromal biomarkers may refine patient stratification and facilitate personalized treatment strategies.

Background/Objectives: Quality of life (QoL) and functional recovery are essential outcomes in patients undergoing rectal cancer surgery. In addition to oncological results, bowel dysfunction and stoma-related issues may significantly affect postoperative well-being We aimed to evaluate 1 and 6 months postoperatively QoL changes and functional outcomes in rectal cancer who underwent curative surgical treatment sphinc-ter-preserving surgeries (SPS) or abdominoperineal resection (APR). Owing to its impact on QoL, several functions were assessed using the Low Anterior Resection Syndrome (LARS) score. Methods: This retrospective observational study consisted of 99 patients which under-went curative rectal cancer surgery, of which 38 patients had colostomy, and 61 no co-lostomy. To assess patient-reported outcomes related to QoL, the EORTC QLQ-C30 questionnaire, QLQ-CR29 questionnaire, and LARS score were sent to the patients at 1 and 6 months postoperatively. Changes over time were analyzed using paired statistical tests, and subgroup analyses were performed according to colostomy status and surgical approach. Results: Significant improvements were observed in the global health status and all major functional domains between 1 and 6 months postoperatively. The global health status increased from 74.9% to 86.5% (p < 0.001). Symptom burden decreased signifi-cantly, particularly for fatigue (−18.31), pain (−14.48), diarrhea (−12.46), and insomnia (−11.45), representing clinically meaningful improvements. Patients who underwent abdominoperineal resection or resection with colostomy had lower QoL scores at 1 month but showed substantial improvement at 6 months, becoming comparable to those who underwent SPS. LARS outcomes demonstrated progressive functional recovery, with the proportion of patients without LARS increasing from 39 to 46, while major LARS decreased from 7 to 3 patients. However, approximately 40% of patients in the SPS group continued to report moderate-to-severe LARS symptoms. Conclusions: In this study, QoL and bowel function improved significantly during the first 6 months after colorectal cancer surgery. Although most patients demon-strated recovery, persistent bowel dysfunction and stoma-related challenges remain important issues. These findings highlight the need for comprehensive postoperative care and routine assessment of both QoL and functional outcomes.

Background: The COVID-19 pandemic profoundly disrupted healthcare systems worldwide, raising concerns regarding delays in cancer diagnosis and treatment. How these disruptions affected breast cancer care during and after the pandemic remains incompletely understood, particularly in Eastern European oncology centers. Methods: We conducted a retrospective cohort study of breast cancer patients treated at the Oncological Institute of Bucharest, comparing a pandemic cohort (n = 73) with a post-pandemic cohort (n = 99) regarding age at diagnose, tumor laterality, tumor location, tumor stage, and time intervals across the diagnostic and treatment pathways. We measured the intervals between: GP referral and the patien’s first presentation to the surgery unit; imaging diagnosis; the date of biopsy or surgery, biopsy result, and initiation of neoadjuvant treatement; the end of neoadjuvant treatement and surgery; surgery and adjuvant treatment; and the interval of time between chemotherapy sessions. Results: Between the two cohorts, the median age was similar (56 [47–67] vs. 59 [50–68] years). Similarities were also found in tumor laterality and quadrant location. In the post-pandemic cohort, 31.3% of patients were diagnosed with advanced stages, compared with 20.5% in the pandemic cohort, although this difference did not reach statistical significance. Our study showed that chemotherapy delivery was more efficient post-pandemic, with shorter intervals between treatment sessions (18 [17–19] vs. 21 [21–22] days). Referral-to-presentation times were also shorter post-pandemic (3 [1–8] vs. 6 [2–10] days). In contrast, during the post-pandemic year, the interval between the end of neoadjuvant therapy and surgery, remained prolonged. Conclusions: During the COVID-19 pandemic, breast cancer care at a major oncology Romanian center was preserved through adapted clinical pathways. We also established that delays in surgical treatment happened in the post-pandemic period and a higher percentage of advanced-stage disease cases were diagnosed. Our findings may suggest that pre-hospital delays and residual system constraints contributed to stage migration in the post-pandemic group rather than deficiencies in oncology care.

Introduction: The occurrence of a second primary lung cancer after head and neck cancer is a challenge for multidisciplinary teams, since the development of a second lung cancer negatively affects the survival rate of patients with head and neck cancer. Case Presentation: This article presents the case of a patient with a double location of cancer: inoperable stage III nasopharyngeal carcinoma, biopsied in December 2017 (non-keratinizing nasopharyngeal carcinoma), treated by means of radiotherapy and chemotherapy (2018–2021), and stage IV lung cancer (squamous carcinoma) with lung metastases, diagnosed in December 2021, treated using polychemotherapy, subsequent maintenance monochemotherapy, radiotherapy of the thorax, and subsequent maintenance monochemotherapy with a favorable result. The patient was still under treatment as of February 2025, the date of the preparation of the current article. Discussion and Literature Review: Regarding the location of the second metachronous cancer, studies show that the most frequent locations are the lungs and the esophagus, with the main causes being alcohol consumption and smoking. Therefore, these patients should be monitored by screening the respiratory and digestive tracts, especially in men, in order to identify a second cancer, either synchronous or metachronous, in an early stage. Conclusions: Educating the patient with head and neck cancer regarding quitting smoking and cutting out alcohol, as well as conducting a follow-up survey, may reduce the incidence of multiple primaries. Moreover, the multidisciplinary management of second primary lung malignancies in patients with head and neck cancer may lead to long-term disease monitoring.

Hydrocephalus is a condition with a major impact on the noble cerebral substance, which, in the absence of a rapid and effective solution, generates significant morbidity and mortality. It is an eminently surgical pathology. The surgical solutions imagined are very numerous: ventriculo-cisternostomies, ventriculoperitoneal shunts, ventriculocardiac shunts, ventriculopleural shunts, ventriculobiliary shunts, ventriculovesical shunts, lumboperitoneal shunts, etc., with broader or narrower indications, sometimes with complications that can limit/restrict the procedure, requiring successive revisions or replacement of the method. Testing the viability and durability of each method imagined has been a constant concern during decades of neurosurgical practice. The occurrence of limited efficacy or complications recorded for each method in particular has generated attempts to improve and optimise the surgical technique, successive revisions of the method, or the choice of another surgical technique. The test of time has confirmed that the ventriculoperitoneal and ventriculocardiac shunts are the most viable and indicated in most etiopathogenic entities of hydrocephalus. This aspect has not limited the concerns for finding alternative surgical treatment solutions for situations in which their efficacy is exceeded or compromised. Ventriculoepiploic shunt, transomphalic extraperitoneal ventriculoportal shunt, and right transcephalic ventriculosubclavicular/ventriculocaval/ventriculocardiac shunt are innovative methods that may represent backup solutions in case of therapeutic failure.

Background and Clinical Significance: Spontaneous abdominal wall hematoma following violent coughing is a rare condition that poses a sometimes difficult therapeutic challenge, with surgical intervention often necessary in severe cases. This report aims to shed light on this rare but severe affection and raise the medical community’s interest by detailing the pathophysiology, management strategies, and outcome of spontaneous abdominal wall hematoma. Case Presentation: The basis for our paper was a comprehensive retrospective analysis of three cases treated in our surgical departments. We rigorously reviewed their clinical notes and imaging examinations to ensure the accuracy and reliability of our findings. Conclusions: These case reports underscore the challenging nature of such hematomas. Clinicians should be aware of this pathology, as it can be life-threatening. Our successful management of these cases shows that it is possible to effectively manage difficult clinical situations with timely intervention.

Vulvar cancer is one of the rarest gynecological malignancies. The development of this condition can be associated with either dysplasia linked to human papillomavirus (HPV), primarily affecting younger women, or vulvar dermatoses such as lichen sclerosus, which predominantly affect older women. Over the last decade, the incidence of vulvar cancer has risen by 0.6% annually, while the relative survival rate has declined. Although metastasis to the vulva is uncommon, it can occur, particularly from cancers in nearby organs such as the cervix, bladder, rectum, or anus. More rarely, metastases from breast cancer and renal cell carcinoma have been reported in the vulva. Vaginal metastases from clear cell renal carcinoma are especially rare. In this article, we present the case of a 56-year-old patient diagnosed with clear cell renal carcinoma, who came to our clinic with a lesion on the right labia, which was identified as a metastasis originating from the kidney. Given the rarity of genital metastases in renal cancer, such cases should be examined and discussed to encourage further research and studies.