Objective: The objective of this study was to evaluate the association between cervical management strategies, specifically pessary placement, cervical cerclage, or expectant management, and gestational age at delivery in twin pregnancies and to assess the prognostic value of cervical characteristics for early preterm birth (<33 weeks). Methods: We conducted a retrospective cohort study including 120 twin pregnancies managed at a tertiary referral center between 2019 and 2024. Pregnancies with positive vaginal or cervical microbiological cultures or abnormal cervical cytology were excluded. The management strategy was selected based on cervical characteristics and clinical judgment. Gestational age at delivery was compared across intervention groups using descriptive statistics, kernel density plots, boxplots, and Kaplan-Meier survival analysis. Multivariable Cox proportional hazards regression was performed to estimate adjusted hazard ratios (HRs) for early delivery, including intervention type and cervical parameters (length, diameter, and funneling). Results: Overall, 26 of 120 pregnancies (21.6%) resulted in delivery before 33 weeks. Pessary placement was associated with longer gestational duration compared with cerclage or expectant management. Kaplan-Meier analysis demonstrated a clear separation of survival curves by intervention group, with the pessary group maintaining pregnancy to later gestational ages (log-rank p < 0.001). In multivariable Cox regression analysis, pessary use was associated with a significantly lower hazard of early delivery compared with cerclage (HR = 0.088, 95% CI: 0.035-0.220; p < 0.001). Expectant management showed a trend toward an increased risk of early delivery (HR = 2.44; p = 0.067). Cervical length and diameter were not independently associated with early delivery after adjustment for intervention type. Funneling was associated with a lower hazard of early delivery, a finding that warrants cautious interpretation. Conclusions: In this retrospective cohort of twin pregnancies without microbiological evidence of infection, pessary placement was associated with prolonged gestation and a lower hazard of early preterm delivery compared with cerclage or expectant management. These findings support a personalized, risk-adapted approach to cervical intervention selection in twin pregnancies. Prospective, randomized studies incorporating etiologic stratification are needed to confirm these associations and guide clinical practice.

Background: Age-related vestibular decline frequently accompanies presbycusis, and older adults undergoing cochlear implantation (CI) may be particularly vulnerable to postoperative dizziness due to a reduced compensatory capacity and a higher burden of comorbidities. Although CI is an effective treatment for severe-to-profound sensorineural hearing loss in the elderly, its impact on vestibular function remains a critical concern. This study aimed to compare pre and postoperative vestibular performance in older patients (≥65 years) versus younger adults undergoing CI in order to identify the risk factors for postoperative vestibular deterioration and critical issues that characterize this category and carry out personalized preoperative counseling. Methods: In this monocentric observational study, adults undergoing CI were divided into two groups: older patients (OPS, ≥65 years) and younger patients (YPS, <65 years). Vestibular function was assessed preoperatively and one month postoperatively through a Dizziness Handicap Inventory (DHI), history of recurrent falls, clinical examination, video head impulse test (VHIT), bithermal caloric testing, and computerized dynamic posturography (Sensory Organization Test, SOT). Risk factors for postoperative vestibular worsening were analyzed using ANOVA test and chi-square statistics, with significance set at p < 0.05. Results: A total of 63 patients were included, with 18 surgeries involving OPS and 45 involving YPS. Preoperatively, OPS showed significantly higher rates of vestibular abnormalities on caloric testing (55.5% vs. 17.7% bilateral hyporeflexia, p < 0.05) and a higher prevalence of recurrent falls (33.3% vs. 4.4%, p < 0.05). Early postoperative dizziness (DHI1) increased significantly in both groups, but age ≥ 65 was a risk factor for ≥10% worsening (OR 2.2, p < 0.05). At one month, YPS returned to baseline DHI values, whereas OPS showed persistent dizziness with significantly higher DHI2 scores (29.2 vs. 12.9, p < 0.05). Vestibular worsening was identified in 33.3% of VHIT assessments and 44.4% of caloric tests in OPS, with caloric testing proving more sensitive than VHIT. Implantation on the better-functioning vestibular side and the presence of ≥3 comorbidities increased the likelihood of persistent postoperative dizziness. Conclusions: Older age is a significant risk factor for persistent dizziness and vestibular impairment one month after CI. Given the reduced compensatory capacity typical of older adults, vestibular assessment should play a central role in preoperative decision-making, particularly for side selection. Bithermal caloric stimulation is recommended as the most sensitive tool for detecting clinically relevant vestibular changes. Preoperative counseling for older CI candidates should include a detailed discussion of vestibular risks and the possible need for postoperative rehabilitation.

Critical closing pressure (CCP) and the vascular waterfall have long been used to explain perfusion failure in shock, yet their physiological meaning has been inconsistently interpreted. CCP is frequently treated as a continuous downstream pressure and inserted into formulas such as mean arterial pressure (MAP) - CCP, implying that a collapse threshold behaves like an opposing pressure even when vessels remain open. Drawing on classical vascular mechanics, whole-bed flow studies, microvascular models, and contemporary clinical physiology, we show that this interpretation is incorrect. Tone-dependent arteriolar collapse does not behave as a Starling resistor: CCP is a threshold at which smooth-muscle tension exceeds intraluminal pressure and vessels close, not a pressure governing flow in patent vessels. Perfusion becomes heterogeneous because different vascular beds reach their collapse thresholds at different pressures (via excessive tone, extrinsic compression, or profound hypotension), disconnecting macro-haemodynamics from microcirculatory flow. This explains why systemic variables such as MAP and systemic vascular resistance (SVR) may appear adequate even while tissues are under-perfused, a phenomenon now termed haemodynamic incoherence. Reframing CCP as a binary collapse threshold resolves longstanding contradictions in the literature, clarifies why MAP-centred targets often fail, and unifies the behaviour of shock states within a four-interface model of circulatory coupling. Therapeutically, the aim is not to "restore a waterfall" but to reopen closed vascular territories by lowering excessive tone, relieving external pressure, or raising truly low arterial inflow. This mechanistic reinterpretation provides a more coherent, physiologically grounded approach to personalised perfusion management in critical illness.

Cancer of unknown primary (CUP) is evolving from a diagnosis of exclusion treated with empirical chemotherapy to a molecularly defined entity amenable to precision-based interventions. This heterogeneous entity, comprising 2–3% of all metastatic malignancies, encompasses diverse cancers with clinically occult primary sites at diagnosis after a thorough workup. Recent landmark trials including CUPISCO and Fudan CUP-001 have demonstrated significant survival improvements with molecularly guided therapies compared to empirical chemotherapy, fundamentally enhancing and complementing traditional organ-centric treatment paradigms. This review synthesizes the current evidence supporting molecular diagnostics, tumor-agnostic therapies, and precision-based approaches in CUP management. We examine the clinical utility of comprehensive genomic profiling, gene expression profiling, and liquid biopsy technologies, while addressing implementation challenges and future directions. The integration of molecular tumor boards and the emergence of tissue/tissue-of-origin agnostic therapies herald a new era where CUP transitions from therapeutic nihilism to personalized oncology. As molecular technologies advance and targeted therapies proliferate, CUP may no longer represent a diagnosis of exclusion but rather an opportunity for molecularly informed precision care.

Artificial intelligence (AI) is rapidly reshaping gastrointestinal (GI) surgery by enhancing decision-making, intraoperative performance, and postoperative management. The integration of AI-driven systems is enabling more precise, data-informed, and personalized surgical interventions. This review provides a state-of-the-art overview of AI applications in GI surgery, organized into four key domains: surgical simulation, surgical computer vision, surgical data science, and surgical robot autonomy. A comprehensive narrative review of the literature was conducted, identifying relevant studies of technological developments in this field. In the domain of surgical simulation, AI enables virtual surgical planning and patient-specific digital twins for training and preoperative strategy. Surgical computer vision leverages AI to improve intraoperative scene understanding, anatomical segmentation, and workflow recognition. Surgical data science translates multimodal surgical data into predictive analytics and real-time decision support, enhancing safety and efficiency. Finally, surgical robot autonomy explores the progressive integration of AI for intelligent assistance and autonomous functions to augment human performance in minimally invasive and robotic procedures. Surgical AI has demonstrated significant potential across different domains, fostering precision, reproducibility, and personalization in GI surgery. Nevertheless, challenges remain in data quality, model generalizability, ethical governance, and clinical validation. Continued interdisciplinary collaboration will be crucial to translating AI from promising prototypes to routine, safe, and equitable surgical practice.

Background: Major depressive disorder (MDD) is often accompanied by generalized anxiety disorder (GAD), a comorbidity linked to greater illness burden and potentially poorer outcomes. Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are established treatments for MDD, yet the impact of comorbid GAD and concomitant medications remains unclear. This study aimed to compare rTMS/iTBS treatment outcomes between patients with MDD with and without comorbid GAD, and to examine the association between concomitant psychotropic medication use, stimulation protocol, and treatment response in a real-world clinical setting. Methods: We conducted a retrospective observational analysis using registry data from 108 patients (MDD + GAD: n = 36; MDD only: n = 72). Patients received either Left-iTBS or Right-rTMS. Baseline severity, percentage change in Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAMD-17) scores, response, and remission were assessed. Logistic and linear regression models adjusted for age, sex, and baseline severity were applied. Sensitivity analyses stratified by stimulation protocol and benzodiazepine (BDZ) use were performed. Results: Baseline severity did not differ between groups. MADRS reduction was numerically lower in the comorbid GAD group (48.3% vs. 52.7%, p = 0.09), whereas HAMD-17 reduction was comparable. Response and remission rates did not differ significantly. Medication use and stimulation protocol did not show statistically significant independent associations with outcomes. Sensitivity analyses confirmed equivalent outcomes between Left-iTBS and Right-rTMS. BDZ users showed a non-significant trend toward lower MADRS improvement and remission. Conclusions: rTMS/iTBS produced substantial clinical improvement and was well tolerated in both patients with MDD and those with MDD comorbid with GAD. Although comorbid anxiety showed a modest tendency to attenuate MADRS score reduction, overall response and remission rates were comparable between groups. Neither concomitant medications nor stimulation protocol significantly affected treatment outcomes, while the potential influence of BDZ exposure warrants further investigation.

Background/Objectives: Mechanical neutrality has long been regarded as the principal alignment target in total knee arthroplasty (TKA). However, radiographic neutrality does not necessarily reflect physiological morphology or patient perception. This study aimed to evaluate one-week postoperative patient-perceived lower-limb straightness after unrestricted kinematic alignment (KA) TKA and to examine its relationship with radiographic alignment parameters and functional findings. Methods: A total of 175 patients (203 knees) who underwent unrestricted KA-TKA were retrospectively reviewed. Pre- and postoperative radiographs, clinical assessments, and a study-specific, non-validated questionnaire were analyzed one week postoperatively. Patient perception of straightness was assessed using the Straightness Visual Analog Scale (S-VAS) and the Straightness Satisfaction Visual Analog Scale (SS-VAS). Radiographic parameters included the hip-knee-ankle angle (HKAA), the medial proximal tibial angle (MPTA), the mechanical lateral distal femoral angle (mLDFA), the joint line convergence angle (JLCA), and Coronal Plane Alignment of the Knee (CPAK) patterns. Correlative analyses between VAS scores and radiographic and clinical parameters were examined. Results: Preoperatively, 85% of knees were perceived as bowed, and all were reported as straight after surgery. Among knees not perceived as bowed preoperatively, 60% were newly perceived as straight postoperatively, while 40% remained perceived as straight. Postoperative satisfaction was high (S-VAS 88.9 ± 11.6; SS-VAS 92.3 ± 12.9). Associations between S-VAS/SS-VAS and HKAA were weak but statistically significant, whereas both showed moderate positive correlations with postoperative knee extension (S-VAS r = 0.54; SS-VAS r = 0.59). Conclusions: At one week after surgery, patients tended to perceive lower-limb straightness as being associated with restoration of physiological morphology and improved knee extension rather than with radiographic mechanical neutrality. Patient-perceived straightness reflects an individualized and natural sense of limb alignment ("inherent straightness") and should be interpreted as an exploratory, patient-centered concept based on an early postoperative test, supporting a personalized framework for alignment evaluation in unrestricted KA-TKA.

Background: Embolization is a key therapeutic option in interventional radiology for the management of acute arterial bleeding and solid organ injuries. While various embolic agents exist, there is a persistent clinical need for materials that are not only highly effective but also biocompatible, easy to deliver, and cost-effective. We aim to evaluate a new eco-friendly dry foam agar-based embolization agent (ABEA) in an uncontrolled solid organ hemorrhage model. Material and Methods: Ten pigs underwent a controlled splenic injury. After a 5 min free-bleeding period, five pigs were treated with splenic artery ABEA embolization, while the remaining five received no treatment and served as the control group. Follow-up angiography was performed immediately after embolization and at 5 and 15 min in the treated pigs. Mean arterial pressures and average blood loss volumes were evaluated for 120 min. Results: The control group showed continuous blood loss, leading to a significantly higher total blood loss than the ABEA-treated group (1451 mL vs. 611 mL at 120 min, p < 0.05). Mean arterial pressure (MAP) remained below the hemorrhagic shock threshold throughout the procedure in the control group, validating the model of uncontrolled hemorrhage. In addition, a significant stabilization of MAP was observed in treated pigs, remaining above the critical level of hemorrhagic shock and differed significantly from control group values. Conclusions: Embolization with ABEA maintained MAP above critical levels and significantly reduced blood loss volume in a hemorrhagic model. These results support the technical feasibility and short-term hemostatic performance of ABEA in an acute setting. While preliminary, this proof-of-concept has provided the basis for a validated clinical study currently underway to evaluate its effectiveness and safety in human patients.

Background: Intraventricular tumors represent a minority in the context of brain tumors, but their surgical treatment is particularly complex due to their vascularization and visualization, especially in deep localization. The characteristics of these tumors make them ideal candidates for minimally invasive surgical strategies such as the tubular retractor technique, above all in the elderly population. Objectives: A 1-year multi-center, retrospective case series was performed: the authors describe their preliminary experience using a neuronavigated tubular retractor in the management of 11 cases of intraventricular meningiomas. Methods: Clinical and radiological findings were examined to define the outcomes. We used an alternative tubular retractor system obtained using a modified preexisting general surgery trocar (ENDOPATH XCEL 15 mm trocar) or the NICO System BrainPath. Results: Gross total resection, defined as the removal of all the tumor visible from the brain scans, was achieved in all cases. Ten out of eleven of the patients did not experience major complications or permanent neurological deficits. Four patients presented transitory post-operative agitation, visual blurring and transient hemiparesis. All patients (mean age 72.6 years) were discharged from the hospital in 5-7 days. Conclusions: Our preliminary experience suggests that the use of navigated tubular retractors, by displacing the fibers and hence minimizing the damage to the surrounding cerebral parenchyma, is feasible and safe, representing a minimally invasive technique for a personalized and patient-tailored approach. The use of the selective ultrasonic aspirator makes it possible to excise the tumor through the narrow corridor of the tubular lumen of around 2 cm, and this technique can also be improved using both endoscope and microscope guidance.

Background/Objectives: Cardiac arrhythmias are among the leading causes of sudden cardiac death (SCD). Pathogenic variants in potassium channel genes play a key role in inherited arrhythmia syndromes, yet their contribution in Central Asian populations remains poorly characterized. Methods: We performed targeted next-generation sequencing (NGS) using a 96-gene custom Haloplex panel in 79 Kazakhstani patients with clinically diagnosed arrhythmias, including atrioventricular block, sick sinus syndrome, and atrial fibrillation. Detected variants in potassium channel genes were classified according to ACMG guidelines and correlated with clinical phenotypes. Results: A total of 52 variants were identified across 11 potassium channel genes. Two likely pathogenic variants (KCNH2 p.Cys66Gly and p.Arg176Trp) and six variants of uncertain significance (VUS) in KCNQ1, KCNE2, KCNE3, and KCNJ8 were detected. Two novel previously unreported variants were found in KCNE5 and KCND3. Patients harboring pathogenic variants commonly presented with early-onset arrhythmias or a positive family history of cardiovascular disease. Carriers of KCNH2 variants exhibited mild QT prolongation and recurrent syncope. Conclusions: This is the first genetic study of potassium channel gene mutations in Kazakhstani patients with cardiac arrhythmias. The detection of pathogenic and novel variants highlights the clinical utility of integrating genetic testing into diagnostic and management pathways for arrhythmia syndromes. Population-specific genomic data are essential for improving risk stratification, guiding medication safety, and enabling cascade family screening in Central Asia.