J. Clin. Med., Volume 13, Issue 5 (March-1 2024) – 338 articles

Background: No studies have identified combined biomarkers that may be more reasonable for the assessment of current chemo-immunotherapy in patients with extensive stage small-cell lung cancer (ES-SCLC). Methods: This study was conducted to investigate a combined biomarker with prognostic or predictive value in ES-SCLC. We determined the best independent prognostic biomarker among the four complete blood-count-derived inflammatory biomarkers (CBC-IBs). Subsequently, we analyzed the prognostic or predictive value of combining this independent CBC-IB with PD-L1 (SP142) expression. We prospectively assessed the SP142 analyses in tumor samples at diagnosis. Results: All in all, 55 patients with ES-SCLC were classified into four groups according to the systemic immune inflammation index (SII) (low/high) and SP142 (positive/negative). The best survival was observed in the low-SII/ SP142-positive group, whereas the worst survival was observed in the high-SII/SP142-negative group (p = 0.002). The combined SII-SP142 biomarker was better for predicting both survival and disease progression in patients with ES-SCLC. Conclusions: The combined SII-SP142 biomarker can be readily and universally obtained at a low cost in clinical practice, without requiring advanced genomics technology or specialized expertise. Although further studies are needed to confirm that the combined SII-SP142 biomarker is widely applicable, it should help clinicians to identify the best patients for combined chemotherapy with atezolizumab in ES-SCLC. Full article

Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) in 288 newly diagnosed NSCLC patients. The analysis of the post-vaccination response was performed after vaccination by assessing the frequency of plasmablasts via flow cytometry and by assessing the concentration of specific anti-pneumococcal antibodies using enzyme-linked immunosorbent assays. Results: The results of the study showed that NSCLC patients responded to the vaccine with an increase in the frequencies of plasmablasts and antibodies but to a lesser extent than healthy controls. The immune system response to PCV13 vaccination was better in patients with lower-stage NSCLC. We found higher antibody levels after vaccination in NSCLC patients who survived 5 years of follow-up. Conclusions: We hope that our research will contribute to increasing patients′ and physicians′ awareness of the importance of including PCV13 vaccinations in the standard of oncological care, which will extend the survival time of patients and improve their quality of life. Full article

Inflammatory bowel diseases, comprising Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing, and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody that blocks the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of ‘real-world’ data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists were reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, were reported. This review explores the results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed. Full article

Background: Extended half-life (EHL) factor IX (FIX) concentrates allow for prophylaxis with prolonged dosing intervals and high bleeding protection in persons with hemophilia B. Long-term real-world studies are lacking. Methods: In a retrospective–prospective study, the six-year use of prophylaxis with the EHL recombinant FIX–albumin fusion protein (rIX-FP) was analyzed, comparing outcomes with previous standard half-life (SHL) FIX in patients already on prophylaxis. Results: Prophylaxis with rIX-FP was prescribed in 15 patients (10 severe, 5 moderate; follow-up: 57 ± 17 months). Based on a pharmacokinetic assessment and clinical needs, the first regimen was 47 ± 7 IU/Kg every 9 ± 2 days. All but one patient remained on rIX-FP prophylaxis, adjusting infusion frequency and/or dose; the last prescribed frequency was ≥10 days in 10/13 patients, being reduced in seven and increased in four vs. the first regimen. The weekly FIX dose was unchanged; FIX trough levels were >5% in all patients. The annual infusion number and FIX IU/Kg significantly decreased (~60%) in eight patients previously on SHL FIX prophylaxis, with similar concentrate costs. Very low bleeding rates (most traumatic bleeds and the last quartile of the infusion interval), improved orthopedic and pain scores, unchanged HEAD-US scores and problem joints, and high treatment adherence (>90%) and satisfaction were registered. Conclusions: Personalized, carefully adjusted rIX-FP regimens contribute to the diffusion and optimization of prophylaxis in persons with severe and moderate hemophilia B, with long-term favorable bleeding, joint, and patient-reported outcomes. Full article

Background: Portal vein thrombosis (PVT) is a rare disease with an estimated incidence of 2 to 4 cases per 100,000 inhabitants. The most common predisposing conditions for PVT are chronic liver diseases (cirrhosis), primary or secondary hepatobiliary malignancy, major infectious or inflammatory abdominal disease, or myeloproliferative disorders. Methods: PVT can be classified on the basis of the anatomical site, the degree of venous occlusion, and the timing and type of presentation. The main differential diagnosis of PVT, both acute and chronic, is malignant portal vein invasion, most frequently by hepatocarcinoma, or constriction (typically by pancreatic cancer or cholangiocarcinoma). Results: The management of PVT is based on anticoagulation and the treatment of predisposing conditions. The aim of anticoagulation in acute thrombosis is to prevent the extension of the clot and enable the recanalization of the vein to avoid the development of complications, such as intestinal infarction and portal hypertension. Conclusions: The treatment with anticoagulant therapy favors the reduction of portal hypertension, and this allows for a decrease in the risk of bleeding, especially in patients with esophageal varices. The anticoagulant treatment is generally recommended for at least three to six months. Prosecution of anticoagulation is advised until recanalization or lifelong if the patient has an underlying permanent pro-coagulant condition that cannot be corrected or if there is thrombosis extending to the mesenteric veins. Full article

The essence of treating scar contractures lies in covering the skin deficit after releasing the contractures, typically using flaps or skin grafts. However, the specific characteristics of scar contractures, such as their location, shape, and size, vary among patients, which makes surgical planning challenging. To achieve excellent outcomes in the treatment of scar contractures, we have developed a dimensional classification system for these contractures. This system categorizes them into four types: type 1 (superficial linear), type 2-d (deep linear), type 2-s (planar scar contractures confined to the superficial layer), and type 3 (planar scar contractures that reach the deep layer, i.e., three-dimensional scar contractures). Additionally, three factors should be considered when determining surgical approaches: the size of the defect, the availability of healthy skin around the defect, and the blood circulation in the defect bed. Type 1 and type 2-d are linear scars; thus, the scar is excised and sutured in a straight line, and the contracture is released using z-plasty or its modified methods. For type 2-s, after releasing the scar contracture band, local flaps are indicated for small defects, pedicled perforator flaps for medium defects, and free flaps and distant flaps for large defects. Type 2-s has good blood circulation in the defect bed, so full-thickness skin grafting is also a suitable option regardless of the defect’s size. In type 3, releasing the deep scar contracture will expose important structures with poor blood circulation, such as tendons, joints, and bones. Thus, a surgical plan using flaps, rather than skin grafts, is recommended. A severity classification and treatment strategy for scar contractures have not yet been established. By objectively classifying and quantifying scar contractures, we believe that better treatment outcomes can be achieved. Full article

Background: Sarcopenia is defined as the loss of muscle mass and strength and low physical performance, and it is closely related to the risk of cardiovascular disease and mortality. Pulse pressure (PP) is a biomarker of arterial stiffness and compliance. Elevated PP levels increase the risk of cardiovascular diseases and all-cause mortality. Nevertheless, the association between PP and sarcopenia has not yet been clearly established. Methods: Participant data were extracted from the Korea National Health and Nutrition Examination Survey conducted from 2014 to 2020. The study population was classified into three groups (PP < 40 mmHg, 40 mmHg ≤ PP < 60 mmHg, and PP ≥ 60 mmHg). PP was calculated by deducting the diastolic blood pressure from the systolic blood pressure. For handgrip strength, the maximum value measured with a grip dynamometer was adopted (weak handgrip strength: <28 kg for men, <18 kg for woman; normal handgrip strength: ≥28 kg for men, ≥18 kg for women). To determine the relationship between PP and the prevalence of weak handgrip strength, multiple logistic regression analysis was performed after adjusting for possible confounding factors. Results: The higher PP group had a higher age, body mass index; systolic blood pressure, prevalence of hypertension, diabetes, hyperlipidemia, and metabolic syndrome, and maximum handgrip strength. In all models, the prevalence of weak handgrip strength was significantly higher in the group with PP ≥ 60 mmHg compared to the control group (PP < 40 mmHg). Conclusions: Elevated PP was significantly associated with a higher prevalence of weak muscle strength. Thus, PP monitoring may be used to identify individuals at risk of sarcopenia and is helpful in improving health outcomes. Full article

Background: Currently, transcatheter aortic valve implantation (TAVI) is the standard procedure recommended for patients over 75 years of age with symptomatic aortic valve stenosis. Percutaneous transfemoral (TF) access is the main route used to perform the procedure. Among periprocedural complications, access-related ones are the most frequent, potentially leading to prolonged in-hospital stays and transfusions. Methods: We performed a retrospective analysis of prospectively collected data on consecutive patients undergoing TF-TAVI with the latest generation balloon-expandable transcatheter valve between 2013 and 2022. Results: A total of 600 patients were analyzed, differentiating the population between ultrasound-guided and blind common femoral artery puncture. Valve Academic Research Consortium 3 (VARC-3)criteria were used to report at 30 days and follow-up. In our propensity-matched comparison of the two groups, we found a strong reduction in access-related complications in the echo-guided group, particularly in terms of reduction of major and minor bleedings. We also found a significant trend in reduction of local complications, such as pseudoaneurysms, hematomas, arterio-venous fistulas, dissection of the femoral or iliac arteries, and stenosis. Conclusions: Although there is a lack of consensus on the role of ultrasound-guided puncture, we found better outcomes for patients having an echo-guided puncture of the main access, particularly with regard to access-related complications, early mobilization, and early discharge home. Full article

The transfacet minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a novel approach available for the management of lumbar spondylolisthesis. It avoids the need to manipulate either of the exiting or traversing nerve roots, both protected by the bony boundaries of the approach. With the advancement in operative technologies such as navigation, mapping, segmentation, and augmented reality (AR), surgeons are prompted to utilize these technologies to enhance their surgical outcomes. A 36-year-old male patient was complaining of chronic progressive lower back pain. He was found to have grade 2 L4/5 spondylolisthesis. We studied the feasibility of a trans-Kambin or a transfacet MIS-TLIF, and decided to proceed with the latter given the wider corridor it provides. Preoperative trajectory planning and level segmentation in addition to intraoperative navigation and image merging were all utilized to provide an AR model to guide us through the surgery. The use of AR can build on the safety and learning of novel surgical approaches to spine pathologies. However, larger high-quality studies are needed to further objectively analyze its impact on surgical outcomes and to expand on its application. Full article

Purpose: Clinical evidence suggests an association between comorbidities and outcome in patients with glioblastoma (GBM). We hypothesised that the internal carotid artery (ICA) calcium score could represent a promising prognostic biomarker in a competing risk analysis in patients diagnosed with GBM. Methods: We validated the use of the ICA calcium score as a surrogate marker of the coronary calcium score in 32 patients with lung cancer. Subsequently, we assessed the impact of the ICA calcium score on overall survival in GBM patients treated with radio-chemotherapy. Results: We analysed 50 GBM patients. At the univariate analysis, methyl-guanine-methyltransferase gene (MGMT) promoter methylation (p = 0.048), gross total tumour resection (p = 0.017), and calcium score (p = 0.011) were significant prognostic predictors in patients with GBM. These three variables also maintained statistical significance in the multivariate analysis. Conclusions: the ICA calcium score could be a promising prognostic biomarker in GBM patients. Full article

Background/Objectives: The need for surgical reconstruction of scalp defects following the excision of cutaneous skin cancers is an increasingly common procedure. Particular challenges arise when considering options for reconstruction of large defects not amenable to local skin flap coverage. The use of skin grafts poses the risk of donor site morbidity. This paper investigates the emerging use of Integra^®, a synthetic acellular dermal regeneration template, as an alternative or adjunct to skin grafting in scalp reconstruction. Methods: The study presents a retrospective analysis of 101 patients who underwent Integra^®-based reconstruction of scalp defects. Demographics, procedure details, complications, need for further surgery, and time to healing were evaluated. Results: The overall success rate of the one-stage Integra^®-only procedure was 95%, with a minor complication rate of 30.7%. Anticoagulation medication was identified as an independent risk factor for post-operative infection, while previous head and neck radiotherapy and increased defect depth were associated with the requirement for a second-stage skin graft. Conclusions: These findings support the consideration of Integra^® as a safe and viable alternative for both partial and full thickness scalp defects in a select cohort of complex highly co-morbid patients, reducing complications and the need for additional procedures. Full article

A prolonged preoperatory aPTT in children is often the cause of a delay of scheduled surgeries and the repetition of multiple blood tests, with the consequent wasting of resources and significant discomfort for children and parents. The aim of this review is to analyze the situations in which an isolated prolongation of aPTT is found during preoperative evaluation in children, especially when it is due to the presence of antiphospholipid antibodies, providing the readers with the keys to interpret this situation and the possibility to correctly evaluate the hemorrhagic risk of a patient. Full article

In this comprehensive review, we delve into the significance of multimodal imaging in diagnosing and managing complications of congenital optic disc anomalies. While the fundus examination is the gold standard tool in the diagnosis of these pathologies, spectral domain (SD) optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) could shed light on the pathogenesis and treatment. Moreover, this review seeks to offer a comprehensive insight into the multimodal approach of these rare congenital pathologies. In conclusion, congenital anomalies of the optic nerve represent a major challenge for ophthalmologists. Further research could be useful to clarify the pathophysiology of these diseases and define a correct and more specific treatment approach. Full article

Background: Aging is a key risk factor for atherosclerosis progression that is associated with increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity, quality of life, and it is associated with reduced life expectancy. As most multicenter randomized trials exclude elderly and very elderly patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home, there is insufficient data on the management of older patients presenting with atherosclerotic lesions outside coronary territory. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment. In addition, due to a variety of severe comorbidities in the elderly, the average daily number of pills taken by octogenarians exceeds nine. Polypharmacy frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and non-adherence. Therefore, we have attempted to gather data on the medical treatment in patients with extra-cardiac atherosclerotic lesions indicating where there is some evidence of the management in elderly patients and where there are gaps in evidence-based medicine. Public PubMed databases were searched to review existing evidence on the effectiveness of lipid-lowering, antithrombotic, and new glucose-lowering medications in patients with extra-cardiac atherosclerotic occlusive disease. Full article

The early and accurate stratification of intracranial cerebral artery stenosis (ICAS) is critical to inform treatment management and enhance the prognostic outcomes in patients with cerebrovascular disease (CVD). Digital subtraction angiography (DSA) is an invasive and expensive procedure but is the gold standard for the diagnosis of ICAS. Over recent years, transcranial color-coded Doppler ultrasound (TCCD) has been suggested to be a useful imaging method for accurately diagnosing ICAS. However, the diagnostic accuracy of TCCD in stratifying ICASs among patients with CVD remains unclear. Therefore, this systematic review and meta-analysis aimed at evaluating the diagnostic accuracy of TCCD in the stratification of intracranial steno-occlusions among CVD patients. A total of six databases—Embase, CINAHL, Medline, PubMed, Google Scholar, and Web of Science (core collection)—were searched for studies that assessed the diagnostic accuracy of TCCD in stratifying ICASs. The meta-analysis was performed using Meta-DiSc 1.4. The Quality Assessment of Diagnostic Accuracy Studies tool version 2 (QUADAS-2) assessed the risk of bias. Eighteen studies met all of the eligibility criteria. TCCD exhibited a high pooled diagnostic accuracy in stratifying intracranial steno-occlusions in patients presenting with CVD when compared to DSA as a reference standard (sensitivity = 90%; specificity = 87%; AUC = 97%). Additionally, the ultrasound parameters peak systolic velocity (PSV) and mean flow velocity (MFV) yielded a comparable diagnostic accuracy of “AUC = 0.96”. In conclusion, TCCD could be a noble, safe, and accurate alternative imaging technique to DSA that can provide useful diagnostic information in stratifying intracranial steno-occlusions in patients presenting with CVD. TCCD should be considered in clinical cases where access to DSA is limited. Full article

Background: Early-onset myopia increases the risk of irreversible high myopia. Methods: This study systematically evaluated the efficacy and safety of low-dose atropine for myopia control in children with premyopia through meta-analysis using random-effects models. Effect sizes were calculated using risk ratios (RRs) with 95% confidence intervals (CIs). Comprehensive searches of PubMed, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov were conducted until 20 December 2023, without language restrictions. Results: Four studies involving 644 children with premyopia aged 4–12 years were identified, with atropine concentrations ranging from 0.01% to 0.05%. The analysis focused on myopia incidence and atropine-related adverse events. Lower myopia incidence (RR, 0.62; 95% CI, 0.40–0.97 D/y; p = 0.03) and reduction in rapid myopia shift (≥0.5 D/1y) (RR, 0.50; 95% CI, 0.26–0.96 D/y; p < 0.01) were observed in the 12–24-month period. Spherical equivalent and axial length exhibited attenuated progression in the atropine group. No major adverse events were detected in either group, whereas the incidence of photophobia and allergic conjunctivitis did not vary in the 12–24-month period. Conclusions: Our meta-analysis supports atropine’s efficacy and safety for delaying myopia incidence and controlling progression in children with premyopia. However, further investigation is warranted due to limited studies. Full article

The management of mechanical ventilation (MV) remains a challenge in intensive care units (ICUs). The digitalization of healthcare and the implementation of artificial intelligence (AI) and machine learning (ML) has significantly influenced medical decision-making capabilities, potentially enhancing patient outcomes. Acute respiratory distress syndrome, an overwhelming inflammatory lung disease, is common in ICUs. Most patients require MV. Prolonged MV is associated with an increased length of stay, morbidity, and mortality. Shortening the MV duration has both clinical and economic benefits and emphasizes the need for better MV weaning management. AI and ML models can assist the physician in weaning patients from MV by providing predictive tools based on big data. Many ML models have been developed in recent years, dealing with this unmet need. Such models provide an important prediction regarding the success of the individual patient’s MV weaning. Some AI models have shown a notable impact on clinical outcomes. However, there are challenges in integrating AI models into clinical practice due to the unfamiliar nature of AI for many physicians and the complexity of some AI models. Our review explores the evolution of weaning methods up to and including AI and ML as weaning aids. Full article

A very low incidence of acute kidney injury (AKI) has been observed in COVID-19 patients purposefully treated with early pressure support ventilation (PSV) compared to those receiving mainly controlled ventilation. The prevention of subdiaphragmatic venous congestion through limited fluid intake and the lowering of intrathoracic pressure is a possible and attractive explanation for this observed phenomenon. Both venous congestion, or “venous bagging”, and a positive fluid balance correlate with the occurrence of AKI. The impact of PSV on venous return, in addition to the effects of limiting intravenous fluids, may, at least in part, explain this even more clearly when there is no primary kidney disease or the presence of nephrotoxins. Optimizing the patient–ventilator interaction in PSV is challenging, in part because of the need for the ongoing titration of sedatives and opioids. The known benefits include improved ventilation/perfusion matching and reduced ventilator time. Furthermore, conservative fluid management positively influences cognitive and psychiatric morbidities in ICU patients and survivors. Here, it is hypothesized that cranial lymphatic congestion in relation to a more positive intrathoracic pressure, i.e., in patients predominantly treated with controlled mechanical ventilation (CMV), is a contributing risk factor for ICU delirium. No studies have addressed the question of how PSV can limit AKI, nor are there studies providing high-level evidence relating controlled mechanical ventilation to AKI. For this perspective article, we discuss studies in the literature demonstrating the effects of venous congestion leading to AKI. We aim to shed light on early PSV as a preventive measure, especially for the development of AKI and ICU delirium and emphasize the need for further research in this domain. Full article

Background: Incisor retraction is often a crucial phase in ongoing orthodontic treatment, with significant implications for alveolar remodeling mechanisms. There are two prevailing theories which seek to explain this. According to the first, teeth move with the bone, while according to the second, teeth move within the bone. This systematic review seeks to assess morphometric changes in the maxillary alveolar process resulting from incisor retraction following premolar extraction and to evaluate the potential for bone remodeling associated with orthodontic movement. Methods: The study was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The following electronic databases were searched: PubMed, Google Scholar, Web of Science EMBASE and the Cochrane Central Register of Controlled Trials. The databases were searched using the following keywords: “Bone remodeling and retraction of incisors”, “Alveolar bone and incisor retraction”, “Bone thickness and incisor retraction”, and “Bone changes and orthodontic treatment”. Search filters were utilized to identify relevant papers and articles written in English and published during the last 10 years. Based on the information provided in their abstracts, papers and articles were selected according to the following criteria: randomized clinical trials (RCTs), controlled clinical prospective trials (CCTs), and retrospective studies. Articles unrelated to the study’s scope or failing to meet inclusion criteria were excluded. These generally comprised individual case reports, case series reports, literature reviews, experimental studies, studies with limited data (including conference abstracts and journal writings), studies involving an unrepresentative group of patients (less than 10 patients), studies concerning patients with syndromes, and animal experiments. The remaining articles which were deemed relevant underwent comprehensive reference review and such journals as the American Journal of Orthodontics, Dentofacial Orthopedics, International Orthodontics, Journal of Clinical Orthodontics, and Angle Orthodontist were manually searched. Results: Seven articles meeting the inclusion criteria articles were selected for final evaluation, with a total of 284 participants, including 233 women and 51 men. During the analysis of the results included in the publications, a lack of homogeneity was observed, rendering a reliable statistical analysis and heterogeneity assessment unobtainable. Noteworthy disparities in methodologies and measurements posed a risk of drawing inappropriate conclusions. Consequently, emphasis was placed on qualitative analysis, emphasizing the need for standardization in future studies of a similar nature, to enable valid and comparable analyses. Conclusions: The research findings incorporated in this review demonstrate that significant bone loss occurs because of incisor retraction, which diminishes distance between the bone surface and the root surface on the palatal aspect. The magnitude of this change may vary, contingent upon both the extent of incisor displacement and alterations in their inclination, thereby affecting the positioning of the root tips. This change is significantly higher in adults than in growing adolescents. The rationale behind this assertion lies in the widely recognized phenomenon of declining cellular activity with advancing age. The decrease in the speed and intensity of cellular changes may explain the diminished capacity for remodeling as patient age increases. There is ongoing discourse regarding alterations in the volume of bone on the labial aspect of the alveolar process. Further research is necessary to measure whether bone remodeling during orthodontic movement is contingent upon other factors, such as the speed and biomechanics of retraction, the level of applied orthodontic force, and the patient age. Full article

Background: Temporomandibular joint disorder (TMD) is a common medical condition. Cone beam computed tomography (CBCT) is effective in assessing TMD-related bone changes, but image noise may impair diagnosis. Emerging deep learning reconstruction algorithms (DLRs) could minimize noise and improve CBCT image clarity. This study compares standard and deep learning-enhanced CBCT images for image quality in detecting osteoarthritis-related degeneration in TMJs (temporomandibular joints). This study analyzed CBCT images of patients with suspected temporomandibular joint degenerative joint disease (TMJ DJD). Methods: The DLM reconstructions were performed with ClariCT.AI software. Image quality was evaluated objectively via CNR in target areas and subjectively by two experts using a five-point scale. Both readers also assessed TMJ DJD lesions. The study involved 50 patients with a mean age of 28.29 years. Results: Objective analysis revealed a significantly better image quality in DLM reconstructions (CNR levels; p < 0.001). Subjective assessment showed high inter-reader agreement (κ = 0.805) but no significant difference in image quality between the reconstruction types (p = 0.055). Lesion counts were not significantly correlated with the reconstruction type (p > 0.05). Conclusions: The analyzed DLM reconstruction notably enhanced the objective image quality in TMJ CBCT images but did not significantly alter the subjective quality or DJD lesion diagnosis. However, the readers favored DLM images, indicating the potential for better TMD diagnosis with CBCT, meriting more study. Full article

(1) Purpose: The incidence of anterior cruciate ligament (ACL) ruptures in children and adolescents has considerably increased during the last decades due to higher levels of competitive athletic activity, and early sport specialization and professionalization. Contemporary ACL reconstruction techniques have recently been subject to renewed interest in this population. The objective of this study is to report the short- and mid-term results of our physis-sparing ACL reconstruction technique using an “over the top” technique associated with a modified Lemaire procedure. (2) Methods: A retrospective series of 12 junior soccer players who presented to our clinic with a torn ACL between January 2019 and September 2021 was reviewed. The inclusion criteria were patients under 15 years with open tibial and femoral physes, with a stable contralateral knee, a minimum follow-up of 6 months, and a time frame from injury to surgery of <3 months. Patients with previous knee surgery, structural concomitant injuries, muscular, neurological, or vascular abnormalities, or hypersensitivity to metal alloys were excluded. The functional evaluation was performed using the International Knee Documentation Committee (IKDC) rating, Lysholm score, and Tegner activity level. Moreover, clinical and radiological assessments were also performed, including KT-1000 and knee X-rays. (3) Results: We identified 1 female and 11 male patients with ACL tears, with a mean age of 13.17 ± 0.9 months. Concomitant injuries include isolated vertical and bucket-handle tears of the medial meniscus, lateral meniscus tears, bilateral tear of both menisci. The mean follow-up time was 26 ± 12.6 months. The average IKDC, Lysholm and Tegner scores were 93.29 ± 11.04, 95.08 ± 13.2 and 9 ± 0.0 points, respectively. The average KT-1000 score of the participants was 0.96 ± 1.6 points. None of the included patients reported post-surgical complications or required additional surgeries. (4) Conclusions: Our novel ACL reconstruction with LET technique is a safe procedure that resulted in good clinical outcomes, lower failure rate and return to sports in skeletally immature patients. Full article

Background: Baraitser–Winter Syndrome (BRWS) is a rare autosomal dominant condition associated with hearing loss (HL). In the literature, two types of this condition are reported, Baraitser–Winter type 1 (BRWS1) and type 2 (BRWS2) produced by specific pathogenetic variants of two different genes, ACTB for BRWS1 and ACTG1 for BRWS2. In addition to syndromic BRWS2, some pathogenic variants in ACTG1 are associated also to another pathologic entity, the “Autosomal dominant non-syndromic hearing loss 20/26”. In these syndromes, typical craniofacial features, sensory impairment (vision and hearing) and intellectual disabilities are frequently present. Heart anomalies, renal and gastrointestinal involvement and seizure are also common. Wide inter- and intra-familial variety in the phenotypic spectrum is reported. Some phenotypic aspects of these syndromes are not yet fully described, such as the degree and progression of HL, and better knowledge of them could be useful for correct follow-up and treatment. Methods and Results: In this study, we report two cases of children with HL and diagnosis of BRWS and a review of the current literature on HL in these syndromes. Full article

Jaw cysts represent a great matter of interest in oral and maxillofacial surgery. Jaw cyst surgery is a common intervention in oral surgery but, in the case of a multidisciplinary patient, the oral surgeon needs to meet with other specialists. A cyst is an epithelium-lined sac containing fluid and/or semisolid material due to epithelial cell proliferation, degeneration, and liquefaction; the hypertonic solution withdraws liquids from the surrounding tissues, while internal pressure exerts an equal strength on the cyst walls. Dentigerous cysts are the second most common odontogenic cysts after radicular cysts, and commonly few or no symptoms are reported. However, the most common diagnosis for dentigerous cyst is represented by eruption of the affected tooth or accidental diagnosis. Commonly, dentigerous cysts may be related to impacted third molars; in the case of impacted third molars and a dentigerous cyst, the tooth should be removed along with the cyst in the same intervention. Mandibular dentigerous cysts are common in children and adults, while dentigerous cysts are a rare neoformation in elderly patients. Treatment usually involves removal of the entire cyst and the associated unerupted tooth. This intervention may be more difficult if the cyst is large, the third molar is in contact with the mandibular nerve, and/or the patient has a medical history that may represent a relative or absolute contraindication. We present the case of a rare symptomatic manifestation of dentigerous cyst in an elderly patient in treatment with dabigatran therapy; for the treatment of dentigerous cysts in the elderly, we suggest a multidisciplinary approach with the use of the histological examination and a careful follow-up. Full article

Purpose: Mutations in Topoisomerase I–binding RS protein (TOPORS) have been previously documented and have been described to result in pathological autosomal dominant retinitis pigmentosa (adRP). In our study, we describe the various genotypes and clinical/phenotypic manifestations of TOPORS-related mutations of our unique patient population in Rural Appalachia. Methods: The medical records of 416 patients with inherited retinal disease at the West Virginia University Eye Institute who had undergone genetic testing between the years of 2015–2022 were reviewed. Patients found to have pathologic RP and mutations related to TOPORS were then analyzed. Results: In total, 7 patients (ages 12–70) were identified amongst three unique families. All patients were female in our study. The average follow-up period was 7.7 years. A mother (70 yr) and daughter (51 yr) had a novel heterozygous nonsense point mutation in TOPORS c.2431C > T, p.Gln811X (Exon 3) that led to premature termination of the desired protein resulting in early onset vision loss, cataract formation, and visual field restriction. The mother developed a full-thickness macular hole which was successfully repaired. Five other patients were found to have previously described TOPORS mutations. Visual field loss was progressive with age in both cohorts. Conclusions: Seven patients at our institution were identified to have mutations in TOPORS resulting in autosomal dominant retinitis pigmentosa. Two patients were found to have novel truncating mutations in the TOPORS gene resulting in profound night blindness and visual field loss, recurrent macular edema, and in one individual, epiretinal membrane formation leading to a macular hole which was able to be successfully repaired. Full article

Introduction: A practical solution to the incidental unreliability of intraoperative neuromonitoring (IONM) may be the simultaneous neurophysiological recording and control of the surgical field through a camera (the concept of “Real-time” IONM). During “Real-time” IONM, the surgeon is immediately warned about the possibility of damage to the neural structures during, but not after, standard idiopathic scoliosis (IS) corrective surgery procedures (the concept of “Surgeon–neurophysiologist” interactive, verbal IONM). This study aimed to compare the advantages, utilities, reliabilities, and time consumption of the two IONM scenarios. Methods: Studies were performed in two similar groups of patients undergoing surgery primarily due to Lenke 2 idiopathic scoliosis (N = 120), when both IONM approaches were applied. Neurophysiological evaluations of the spinal transmission were performed pre- (T0), intra- (before (T1) and after (T2) surgery), and postoperatively (T3), as well as once in healthy volunteers (control, N = 60). Non-invasive and innovative recordings of the motor evoked potentials (MEPs) bilaterally from the peroneal (PER) nerve and tibialis anterior (TA) muscle were performed with surface electrodes as a result of transcranial magnetic stimulation (TMS) or electrical stimulation (TES) at T0–T3. Results: In both groups, the MEP amplitudes and latencies recorded from the PER nerve were approximately 67% lower and 3.1 ms shorter than those recorded from the TA muscle. The MEP recording parameters differed similarly at T0–T3 compared to the control group. In all patients, the MEP parameters induced by TMS (T0) and TES (T1) did not differ. The MEP amplitude parameters recorded from the TA and PER at T1 and T2 indicated a bilateral improvement in the neural spinal conduction due to the surgical intervention. The TMS-induced MEP amplitude at T3 further increased bilaterally. In both IONM groups, an average 51.8 BIS level of anesthesia did not affect the variability in the MEP amplitude, especially in the PER recordings when the applied TES strength was 98.2 mA. The number of fluctuations in the MEP parameters was closely related to the number of warnings from the neurophysiologist during the transpedicular screw implantation, corrective rod implantation, and distraction, derotation, and compression procedures, and it was higher in the “Surgeon–neurophysiologist” IONM group. The average duration of surgery was shorter by approximately one hour in the “Real-time” IONM group. The number of two-way communications between the surgeon and the neurophysiologist and vice versa in the “Real-time” IONM group decreased by approximately half. Conclusions: This study proves the superiority of using “Real-time” IONM over the standard “Surgeon–neurophysiologist” IONM procedure in increasing the safety and non-invasiveness, shortening the time, and lowering the costs of the surgical treatment of IS patients. The modifications of the MEP nerve-conduction-recording technology with surface electrodes from nerves enable precise and reliable information on the pediatric patient’s neurological condition at every stage of the applied surgical procedures, even under conditions of slight fluctuations in anesthesia. Full article

Endometrial cancer is the most incident gynecological cancer. Lymph node dissemination is one of the most important factors for the patient’s prognosis. Pelvic lymph nodes are the primary site of extra-uterine dissemination in endometrial cancer (EC), setting the 5-year survival to 44–52%. It is standard practice for radiation therapy (RT) and/or chemotherapy (CTX) to be given as adjuvant treatments to prevent the progression of micrometastases. Also, administration of EC patients with RT and/or CTX regimens before surgery may decrease micrometastases, hence the need for lymphadenectomy. The primary aim of the systematic review and meta-analysis is to assess whether adjuvant RT and/or CTX improve oncological outcomes through the management of micrometastases and nodal recurrence. We performed systematic research using the string “Endometrial Neoplasms” [Mesh] AND “Lymphatic Metastasis/therapy” [Mesh]. The methods for this study were specified a priori based on the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Outcomes were 5-year overall survival, progression-free survival, recurrence rate, and complications rate. We assessed the quality of studies using the Newcastle–Ottawa Scale (NOS). A total of 1682 patients with stage I-to-IV EC were included. Adjuvant treatment protocols involved external-beam RT, brachytherapy, and CTX either alone or in combination. The no-treatment group showed a non-statistically significant higher recurrence risk than any adjuvant treatment group (OR 1.39 [95% CI 0.68–2.85] p = 0.36). The no-treatment group documented a non-statistically significant higher risk of death than those who underwent any adjuvant treatment (RR 1.47 [95% CI 0.44–4.89] p = 0.53; I2 = 55% p = 0.000001). Despite the fact that early-stage EC may show micrometastases, adjuvant treatment is not significantly associated with better survival outcomes, and the combination of EBRT and CTX is the most valid option in the early stages. Full article

Background: Percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) are established methods in the treatment of vertebral compression fractures (VCFs). In our manuscript, the target was to evaluate the efficacy of PVPs/PKPs and to determine the implications of potential periprocedural complications. Methods: 280 patients, specifically 194 women (69.3%) and 86 men (30.7%), were enrolled. We used the AO spine fractures classification and the Yeom classification to determine the subtype of cement leakage. Only single-level VCFs of the thoracic or lumbar spine were included. Visual analogue scale (VAS) was assessed preoperatively and regularly after the surgery. Vertebral compression ratio (VBCR) was used to determine postoperative vertebral body collapse. Results: We recorded 54 cases (19.3%) of cement leakage. There was a significant decrease in mean VAS scores (6.82–0.76 in PVPs, 7.15–0.81 in PKPs). The decrease in VBCR was greater in the VP group (4.39%; 84.21–79.82) compared to the KP group (1.95%; 74.36–72.41). Conclusions: No significant difference in the risk of cement leakage when comparing KPs and VPs was found. VPs and KPs provide rapid and significant pain relief in patients with VCFs. Clinically relevant complications of VPs and KPs are rare. Kyphoplasties prevent further vertebral body collapse more effectively compared to vertebroplasties. Full article

Venous thromboembolism (VTE), comprising deep venous thrombosis (DVT) and pulmonary embolism (PE), is a prevalent cardiovascular condition, ranking third globally after myocardial infarction and stroke. The risk of VTE rises with age, posing a growing concern in aging populations. Acute PE, with its high morbidity and mortality, emphasizes the need for early diagnosis and intervention. This review explores prognostic factors for acute PE, categorizing it into low-risk, intermediate-risk, and high-risk based on hemodynamic stability and right ventricular strain. Timely classification is crucial for triage and treatment decisions. In the contemporary landscape, low-risk PE patients are often treated with Direct Oral Anticoagulants (DOACS) and rapidly discharged for outpatient follow-up. Intermediate- and high-risk patients may require advanced therapies, such as systemic thrombolysis, catheter-directed thrombolysis, mechanical thrombectomy, and IVC filter placement. The latter, particularly IVC filters, has witnessed increased usage, with evolving types like retrievable and convertible filters. However, concerns arise regarding complications and the need for timely retrieval. This review delves into the role of IVC filters in acute PE management, addressing their indications, types, complications, and retrieval considerations. The ongoing debate surrounding IVC filter use, especially in patients with less conventional indications, reflects the need for further research and data. Despite complications, recent studies suggest that clinically significant issues are rare, sparking discussions on the appropriate and safe utilization of IVC filters in select PE cases. The review concludes by highlighting current trends, gaps in knowledge, and potential avenues for advancing the role of IVC filters in future acute PE management. Full article

Background: Few data are available concerning the outcome of patients denied venovenous extracorporeal membrane oxygenation (VV-ECMO) relative to severe acute respiratory distress syndrome (ARDS) due to COVID-19. Methods: We compared the 90-day survival rate of consecutive adult patients for whom our center was contacted to discuss VV-ECMO indication. Three groups of patients were created: patients for whom VV-ECMO was immediately indicated (ECMO-indicated group), patients for whom VV-ECMO was not indicated at the time of the call (ECMO-not-indicated group), and patients for whom ECMO was definitely contraindicated (ECMO-contraindicated group). Results: In total, 104 patients were referred for VV-ECMO support due to severe COVID-19 ARDS. Among them, 32 patients had immediate VV-ECMO implantation, 28 patients had no VV-ECMO indication, but 1 was assisted thereafter, and 44 patients were denied VV-ECMO for contraindication. Among the 44 patients denied, 30 were denied for advanced age, 24 for excessive prior duration of mechanical ventilation, and 16 for SOFA score >8. The 90-day survival rate was similar for the ECMO-indicated group and the ECMO-not-indicated group at 62.1 and 61.9%, respectively, whereas it was significantly lower (20.5%) for the ECMO-contraindicated group. Conclusions: Despite a low survival rate, 50% of patients were at home 3 months after being denied for VV-ECMO for severe ARDS due to COVID-19. Full article

Background: Locked plating for distal femur fractures is widely recommended and used. We systematically reviewed clinical studies assessing the benefits and harms of fracture fixation with locked plates in AO/OTA Type 32 and 33 femur fractures. Methods: A comprehensive literature search of PubMed, Embase, Cinahl, Web of Science, and the Cochrane Database was performed. The studies included randomized and non-randomized clinical trials, observational studies, and case series involving patients with distal femur fractures. Studies of other fracture patterns, studies conducted on children, pathological fractures, cadaveric studies, animal models, and those with non-clinical study designs were excluded. Results: 53 studies with 1788 patients were found to satisfy the inclusion and exclusion criteria. The most common harms were nonunion (14.8%), malunion (13%), fixation failure (5.3%), infection (3.7%), and symptomatic implant (3.1%). Time to full weight-bearing ranged from 5 to 24 weeks, averaging 12.3 weeks. The average duration of follow-up was 18.18 months, ranging from 0.5 to 108 months. Surgical time ranged between 40 and 540 min, with an average of 141 min. The length of stay in days was 12.7, ranging from 1 to 61. The average plate length was ten holes, ranging from 5 to 20 holes. Conclusion: This review aimed to systematically synthesize the available evidence on the risk associated with locked plating osteosynthesis in distal femur fractures. Nonunion is the most common harm and is the primary cause of reoperation. The overall combined risk of a major and critical complication (i.e., requiring reoperation) is approximately 20%. Full article