Journal of Clinical Medicine

This prospective, non-randomized, interventional clinical study evaluated the efficacy and safety profile of first-generation iStent bypass implantation versus ab externo canaloplasty, both combined with phacoemulsification, in patients with primary open-angle glaucoma (POAG) after 12-month follow-up. A total of 138 patients with POAG and their 138 eyes (69 phaco-iStent and 69 phacocanaloplasty) were included. Postoperatively at 12 months, the mean intraocular pressure (IOP) decreased from 18.44 ± 3.88 to 15.51 ± 2.50 mmHg and from 17.20 ± 4.04 to 14.97 ± 2.37 mmHg in the phaco-iStent (PiS) and phacocanaloplasty (PC) groups, respectively (p = 0.480). In both groups, 35.7% achieved >20% IOP reduction from baseline. A total of 86% and 71.4% of the eyes were medication-free at 12 months in the PiS and PC groups, respectively. In both groups, all eyes showed improvement in best-corrected visual acuity compared with baseline and demonstrated similar safety profiles throughout the 12-month follow-up period. This study showed equal hypotensive effects of PiS and PC. Both procedures significantly reduced the IOP and the requirement for IOP-lowering medications for at least 12 months postoperatively, with no significant differences between the groups. Full article

Sarcomeric hypertrophic cardiomyopathy (HCM) is a prevalent genetic disorder characterised by left ventricular hypertrophy, myocardial disarray, and an increased risk of heart failure and sudden cardiac death. Despite advances in understanding its pathophysiology, treatment options for HCM remain limited. This narrative review aims to provide a comprehensive overview of current clinical practice and explore emerging therapeutic strategies for sarcomeric HCM, with a focus on cardiac myosin inhibitors. We first discuss the conventional management of HCM, including lifestyle modifications, pharmacological therapies, and invasive interventions, emphasizing their limitations and challenges. Next, we highlight recent advances in molecular genetics and their potential applications in refining HCM diagnosis, risk stratification, and treatment. We delve into emerging therapies, such as gene editing, RNA-based therapies, targeted small molecules, and cardiac myosin modulators like mavacamten and aficamten, which hold promise in modulating the underlying molecular mechanisms of HCM. Mavacamten and aficamten, selective modulators of cardiac myosin, have demonstrated encouraging results in clinical trials by reducing left ventricular outflow tract obstruction and improving symptoms in patients with obstructive HCM. We discuss their mechanisms of action, clinical trial outcomes, and potential implications for the future of HCM management. Furthermore, we examine the role of precision medicine in HCM management, exploring how individualised treatment strategies, including exercise prescription as part of the management plan, may optimise patient outcomes. Finally, we underscore the importance of multidisciplinary care and patient-centred approaches to address the complex needs of HCM patients. This review also aims to encourage further research and collaboration in the field of HCM, promoting the development of novel and more effective therapeutic strategies, such as cardiac myosin modulators, to hopefully improve the quality of life and outcome of patients with sarcomeric HCM. Full article

We conducted a prospective double-blind study to compare two vaginal diagnostic methods in singleton pregnancies with threatened preterm labor (TPL) at the University Hospital of Clermont-Ferrand (France) from August 2018 to December 2020. Our main objective was to compare the diagnostic capacity at admission, in terms of positive predictive value (PPV) and negative predictive value (NPV), of Premaquick^® (combined detection of IL-6/total IGFBP-1/native IGFBP-1) and QuikCheck fFN™ (fetal fibronectin) for delivery within 7 days in cases of TPL. We included 193 patients. Premaquick^® had a sensitivity close to 89%, equivalent to QuikCheck fFN™, but a higher statistical specificity of 49.5% against 38.6% for QuikCheck fFN™. We found no superiority of Premaquick^® over QuickCheck fFN™ in terms of PPV (6.6% vs. 7.9%), with NPV being equivalent in predicting childbirth within 7 days in cases of TPL (98.6% vs. 98.9%). Nevertheless, the combination of positive native and total IGFBP-1 and the combination of all three positive markers were associated with a higher PPV. Our results, though non-significant, support this combined multiple-biomarker approach to improve testing in terms of predictive values. Full article

Purpose: To compare refractive prediction errors between phacotrabeculectomy and phacoemulsification. Methods: Refractive prediction error was defined as the difference in spherical equivalent between the predicted value using the Barrett Universal II formula and the actual value obtained at postoperative one month. Forty-eight eyes that had undergone phacotrabeculectomy (19 eyes, open-angle glaucoma; 29 eyes, angle-closure glaucoma) were matched with 48eyes that had undergone phacoemulsification by age, average keratometry value and axial length (AL), and their prediction errors were compared. The factors associated with prediction errors were analyzed by multivariable regression analyses. Results: The phacotrabeculectomy group showed a larger absolute prediction error than the phacoemulsification group (0.51 ± 0.37 Diopters vs. 0.38 ± 0.22 Diopters, p = 0.033). Larger absolute prediction error was associated with longer AL (p = 0.010) and higher intraocular pressure (IOP) difference (p = 0.012). Hyperopic shift (prediction error > 0) was associated with shallower preoperative anterior chamber depth (ACD) (p = 0.024) and larger IOP difference (p = 0.031). In the phacotrabeculectomy group, the prediction error was inversely correlated with AL: long eyes showed myopic shift and short eyes hyperopic shift (p = 0.002). Conclusions: Surgeons should be aware of the possibility of worse refractive outcomes when planning phacotrabeculectomy, especially in eyes with high preoperative IOP, shallow ACD, and/or extreme AL. Full article

(1) Background: patients who meet current rapid rule-out criteria for myocardial infarction (MI) are considered low risk, yet their management remains nebulous, especially among women. We aimed to examine sex differences in the diagnosis, management, and outcomes of patients meeting the rapid rule-out criteria. (2) Methods: by simulating application of the rapid rule-out MI criteria, we analyzed consecutively triaged men and women with suspected NSTE-ACS who had high-sensitivity cardiac troponin T (hs-cTnT) values that met criteria (n = 11,477), in particular, those who were admitted (n = 3775). (3) Results: men constituted ~55% of triaged patients who met the rule-out criteria, whether admitted or discharged. Men were more likely to be admitted (33.7% vs. 31.9%, p = 0.04), more commonly with hs-cTnT values between level of detection (LOD, 5 ng/ml) and the 99th percentile (59.4% of all admissions vs. 40.5% for women), whereas women were more likely to be admitted with values < level of blank (LOB, 3 ng/mL; 22.9% vs. 9.2% for men). Thirty-day mortality (1 man and 1 woman) and in-hospital MI (9 men vs. 1 woman) were uncommon among admitted patients, yet resource utilization during 3–4 hospitalization days was substantial for both sexes, with men undergoing coronary angiography (6.8% vs. 2.9%) and revascularization (3.4% vs. 1.1%) more commonly. Long-term survival for both men and women, whether admitted or discharged, was significantly worse for hs-cTnT values between LOD and the 99th percentile, even after adjusting for age and cardiovascular comorbidities. (4) Conclusions: reporting actual hs-cTnT values < 99th percentile allows for better risk stratification, especially for women, possibly closing the sex gap. Full article

Background: Knowledge of the natural history and management of hepatic hemangiomas is lacking. The aim of this study was to investigate the natural history of hemangiomas and to elucidate the factors that determine tumor growth and optimal management. Methods: A total of 211 adult patients were enrolled, with follow-up for more than three years. Follow-up was performed with repeated ultrasonography (US) and laboratory tests for liver function and coagulation factors (platelets, prothrombin time (PT), fibrinogen, thrombin–antithrombin III complex (TAT), D-dimer, and fibrin and fibrinogen degradation products (FDP)). Results: Tumor size decreased in 38.9% of patients, showed no change in 31.3%, and increased in 29.8%. The incidence of a size increase was very high in patients under 40 years of age and decreased gradually with age, whereas the incidence of a size decrease increased with age and increased markedly over 60 years of age. The incidence of an increase in size decreased gradually with size enlargement, whereas the incidence of a decrease in size increased markedly with tumor size and further increased rapidly when hemangiomas became larger than 60 mm. Values of TAT, D-dimer, FDP, and Mac-2 binding protein glycosylation isomer (M2BPGi) were closely related to the change in size of hemangiomas. Conclusions: Hemangiomas in older patients (>60 years of age) and larger tumors (>60 mm in size) had a tendency to decrease in size, resulting from the reduction in coagulation disorders and the progression of liver fibrosis. Therefore, the majority of patients with hemangiomas can be safely managed by clinical observation. Full article

Heavy menstrual bleeding (HMB) is a common clinical condition affecting adolescent and adult women and compromising their quality of life. Primary hemostasis disorders, affecting platelet plug formation, can be the underlying cause of HMB. They comprise a heterogeneous group of diseases with Von Willebrand disease (VWD) being the most commonly diagnosed; other disorders in this group that have been linked to HMB include (a) Glanzmann thrombasthenia, (b) Bernard–Soulier syndrome, (c) Hermansky–Pudlak syndrome, (d) immune thrombocytopenia (ITP), and (e) Ehlers–Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD). Diagnosing these diseases can be challenging, as the basic laboratory investigations can be within the normal range. Thus, identification of specific clinical features and a thorough hematologic workup can be very important, providing the correct diagnosis. Proper diagnosis of the underlying disorder is important, as management may vary accordingly. Although disease-specific management guidelines exist for some of these disorders such as VWD and ITP, due to the rarity of most primary hemostasis disorders, the best approach for the management of HMB in these women remains elusive. The goal of this study was to create an informative, comprehensive review of the primary hemostasis disorders that have been linked to HMB. This study provides a summary of the basic published information regarding epidemiology, pathophysiology, clinical phenotype, diagnosis, and treatment of HMB in those diseases and serves as a reference guide for further reading. Full article

Ossification of the posterior longitudinal ligament of the thoracic spine (T-OPLL) causes symptoms including leg and back pain, and motor and sensory deficits. This study retrospectively reviewed 32 patients who initially underwent posterior decompression with instrumented fusion (PDF) for T-OPLL between 2001 and 2012, with 20 qualifying for the final analysis after applying exclusion criteria. Exclusions included unknown preoperative neurological findings, follow-up less than 10 years, or prior spinal surgeries at other levels. Outcomes were assessed using the Japanese Orthopedic Association (JOA) score, recovery rate, and kyphotic angle. The average preoperative JOA score of 3.6 improved to 7.4 at 1 year post-surgery and remained at 7.4 at 10 years, with a recovery rate of 52%. The kyphotic angle at T4–12 increased from 26 degrees preoperatively to 29 degrees postoperatively and to 37 degrees at 10 years. At the fused levels, the angle remained at 26 degrees immediately post-operation and increased to 32 degrees at 10 years. Forty percent of patients required additional surgery, primarily for conditions related to cervical OPLL, such as myelopathy, or lumbar OPLL, such as radiculopathy, or cauda equina syndrome. In conclusion, PDF effectively reduces T-OPLL symptoms over the long term, but the high rate of additional surgeries calls for careful patient follow-up. Full article

Background: The so-called Low Cardiac Output Syndrome (LCOS) is one of the most common complications in pediatric patients with congenital heart disease undergoing corrective surgery. LCOS requires high concentrations of inotropes to support cardiac contractility and improve cardiac output, allowing for better systemic perfusion. To date, serum lactate concentrations and central venous oxygen saturation (ScVO₂) are the most commonly used perfusion markers, but they are not completely reliable in identifying a state of global tissue hypoxia. The study aims to evaluate whether the venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio [P(v-a)CO₂/C(a-v)O₂] can be a good index to predict the development of LCOS in the aforementioned patients, so as to treat it promptly. Methods: This study followed a population of 98 children undergoing corrective cardiac surgery from June 2018 to October 2020 at the Department of Cardiac Surgery of University Hospital Integrated Trust and their subsequent admission at the Postoperative Cardiothoracic Surgery Intensive Care Unit. During the study, central arterial and venous blood gas analyses were carried out before and after cardiopulmonary bypass (CPB) (pre-CPB and post-CPB), at admission to the intensive care unit, before and after extubation, and at any time of instability or modification of the patient’s clinical and therapeutic conditions. Results: The data analysis shows that 46.9% of the children developed LCOS (in line with the current literature) but that there is no statistically significant association between the P(v-a)CO₂/C(a-v)O₂ ratio and LCOS onset. Despite the limits of statistical significance, however, a 31% increase in the ratio emerged from the pre-CPB phase to the post-CPB phase when LCOS is present. Conclusions: This study confirms a statistically significant association between the most used markers in adult patients (serum lactate concentration, ScVO₂, and oxygen extraction ratio—ERO₂) measured in the pre-CPB phase and the incidence of LCOS onset, especially in patients with hemodynamic instability before surgery. Full article

Interleukin (IL)-23 is a central pro-inflammatory cytokine with a broad range of effects on immune responses. IL-23 is pathologically linked to the induction of the production of the pro-inflammatory cytokines IL-17 and IL-22, which stimulate the differentiation and proliferation of T helper type 17 (Th17) cells. Recent discoveries suggest a potential pro-fibrotic role for IL-23 in the development of chronic inflammatory autoimmune diseases characterized by intense fibrosis. In this review, we summarized the biological features of IL-23 and gathered recent research on the role of IL-23 in fibrotic autoimmune conditions, which could provide a theoretical basis for clinical targeting and drug development. Full article

Background: The myocardial uptake of bone-seeking tracers suspicious for transthyretin cardiac amyloidosis (ATTR-CA) can be incidentally detected in patients undergoing bone scintigraphy for noncardiac reasons. We conducted a systematic review and meta-analysis to assess the prevalence of these scintigraphic findings. Methods: A comprehensive literature search was performed using two bibliographic databases (PubMed/MEDLINE and Cochrane Library), searching for articles related to the review question. Eligible articles were selected, and relevant data were extracted by two authors. The pooled prevalence of incidental findings suspicious for ATTR-CA among patients undergoing bone scintigraphy was calculated on a per-patient-based analysis using a random-effects model. The pooled measure was provided with 95% confidence interval (95% CI) values. Results: Among 219 records, 11 articles were selected for the systematic review and 10 for the meta-analysis. The pooled prevalence of incidental findings suspicious for ATTR-CA was 1.1% (95% CI: 0.7–1.4%) with heterogeneity due to the characteristics of the included studies, patients, and index tests. These findings are more prevalent in older men. Conclusions: The prevalence of incidental findings of ATTR-CA among patients undergoing bone scintigraphy is low but not negligible. Nuclear medicine physicians should suggest, in the scintigraphic report, further clinical investigations when these findings are detected. Prospective studies are warranted. Full article

The aim of this multicenter retrospective cohort study was to examine the impact of maternal age on perinatal outcomes in multiparas, stratified according to maternal age in one- and two-year increments. The analysis involved 302,484 multiparas who delivered between the years 2003 and 2021 in four university-affiliated obstetrics departments. Maternal age was considered both as a continuous variable and in two-year intervals, as compared with a comparison group of parturients aged 25–30 years. The study focused on cesarean delivery and neonatal intensive care unit (NICU) admission as primary outcomes. The findings revealed that cesarean delivery rates increased as maternal age advanced, with rates ranging from 6.7% among 25–30 year olds, rising continuously from 13.5% to 19.9% between the age strata of 31 and 42, to exceeding 20% among those aged ≥ 43 years (p < 0.01 for each stratum when compared to 25–30 year old group). Similarly, NICU admission rates rose from 2.7% in the comparison group to 6% in parturients aged 45–46 years (p < 0.01 for each stratum when compared to 25–30 year old group). The study highlights the association between incrementally advanced maternal age and increased rates of maternal and neonatal complications, necessitating global awareness of these implications for family planning decisions and maternal care. Full article

Background: Collagen cross-linking is a fundamental process in dilated cardiomyopathy (DCM) and occurs when collagen deposition exceeds degradation, leading to impaired prognosis. This study investigated the associations of collagen-metabolism biomarkers with left ventricular function and prognosis in DCM. Methods: DCM patients who underwent endomyocardial biopsy, blood sampling, and cardiac MRI were included. The primary endpoint included death, heart failure hospitalization, or life-threatening arrhythmias, with a follow-up of 6 years (5–8). Results: In total, 209 DCM patients were included (aged 54 ± 13 years, 65% male). No associations were observed between collagen volume fraction, circulating carboxy-terminal propeptide of procollagen type-I (PICP), or collagen type I carboxy-terminal telopeptide [CITP] and matrix metalloproteinase [MMP]-1 ratio and cardiac function parameters. However, CITP:MMP-1 was significantly correlated with global longitudinal strain (GLS) in the total study sample (R = −0.40, p < 0.0001; lower CITP:MMP-1 ratio was associated with impaired GLS), with even stronger correlations in patients with LVEF > 40% (R = −0.70, p < 0.0001). Forty-seven (22%) patients reached the primary endpoint. Higher MMP-1 levels were associated with a worse outcome, even after adjustment for clinical and imaging predictors (1.026, 95% CI 1.002–1.051, p = 0.037), but CITP and CITP:MMP-1 were not. Combining MMP-1 and PICP improved the goodness-of-fit (LHR36.67, p = 0.004). Conclusion: The degree of myocardial cross-linking (CITP:MMP-1) is associated with myocardial longitudinal contraction, and MMP-1 is an independent predictor of outcome in DCM patients. Full article

Background: Arthroscopic revision rotator cuff repair (ARRCR) is challenging. Biologic strategies seem to be promising. The aim was to evaluate the effectiveness of the combination of microfractures of the greater tuberosity, augmentation with collagen patch graft, and platelet concentrate injections in ARRCR. Methods: A retrospective comparative study was conducted on patients that underwent ARRCR with a minimum follow-up of two years. Patients in the augmentation group underwent ARRCR combined with microfractures, collagen patch graft, and postoperative subacromial injections of platelet concentrate. A standard rotator cuff repair was performed in the control group. Primary outcome: Constant-Murley score (CMS). Secondary outcomes: disease-specific, health-related quality of life using the Disabilities of the Arm, Shoulder, and Hand (DASH) score; assessment of tendon integrity with magnetic resonance at least six months after surgery. Significance was set at p < 0.05. Results: Forty patients were included. Mean follow-up was 36.2 ± 8.7 months. The mean CMS was greater in the augmentation group (p = 0.022). No differences could be found for DASH score. Healing failure rate was higher in the control group (p = 0.002). Conclusion: Biologic augmentation of ARRCR using a combination of microfractures, collagen patch graft, and subacromial injections of platelet concentrate is an effective strategy in improving tendon healing rate. Level of evidence: retrospective cohort study, level III. Full article

The surgical management of acute and chronic complex diseases involving the aortic arch and the descending thoracic aorta remains challenging. Hybrid procedures associating total open arch replacement and stent-grafting of the proximal descending aorta were developed to allow a potential single-stage treatment, promote remodeling of the downstream aorta, and facilitate a potential second-stage thoracic endovascular aortic repair by providing an ideal landing zone. While these approaches initially used various homemade combinations of available conventional prostheses and stent-grafts, the so-called frozen elephant trunk technique emerged with the development of several custom-made hybrid prostheses. The aim of this study was to review the contemporary outcomes of this technique in the management of complex aortic diseases, with a special focus on procedural planning, organ protection and monitoring, refinements in surgical techniques, and long-term follow-up. Full article