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Purpose: The primary cause of pulp and periapical diseases is the invasion of bacteria into the root canal, which results from the continuous destruction of dental hard tissues. Effective management of infections during root canal therapy necessitates effectively irrigation. This study aims to investigate the effects of two antimicrobial peptides (AMPs), buCaTHL4B and Im-4, on root canal biofilms in vitro. Methods: Two-species biofilms (Enterococcus faecalis and Fusobacterium nucleatum) were selected and anaerobically cultivated. The following treatments were applied: 10 µg/mL buCaTHL4B, 10 µg/mL Im-4, 5 µg/mL buCaTHL4B, 5 µg/mL Im-4, 1 µg/mL buCaTHL4B, 1 µg/mL Im-4, 1% NaOCl, and sterile water. Each group was treated for 3 min. Subsequently, the two strains were co-cultured with 10 µg/mL buCaTHL4B, 10 µg/mL Im-4, 1% NaOCl, and sterile water for 24, 48, and 72 h. The biofilms were examined using confocal laser scanning microscopy (CLSM) with fluorescent staining, and the percentages of dead bacteria were calculated. Quantitative real-time PCR (qRT-PCR) was employed to assess the variations in bacterial proportions during biofilm formation. Results: Compared to 1% NaOCl, 10 µg/mL buCaTHL4B or Im-4 exhibited significantly greater bactericidal effects on the two-species biofilms (p < 0.05), leading to their selection for subsequent experiments. Over a 48-hour period, 10 µg/mL Im-4 demonstrated a stronger antibiofilm effect than buCaTHL4B (p < 0.05). Following a 24-hour biofilm formation period, the proportion of F. nucleatum decreased while the proportion of E. faecalis increased in the sterile water group. In the buCaTHL4B and 1% NaOCl groups, the proportion of F. nucleatum was lower than that of E. faecalis (p < 0.05), whereas in the Im-4 group, the proportion of F. nucleatum was higher than that of E. faecalis (p < 0.05). The proportions of bacteria in the two AMPs groups gradually stabilized after 24 h of treatment. Conclusion: buCaTHL4B and Im-4 exhibited remarkable antibacterial and anti-biofilm capabilities against pathogenic root canal biofilms in vitro, indicating their potential as promising additives to optimize the effectiveness of root canal treatment as alternative irrigants.

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Severe left ventricular outflow tract obstruction (LVOTO) of hypertrophic cardiomyopathy is an acutely life-threatening, must-not miss, cardiology emergency that infrequently presents to the emergency department (ED). Patients with this condition usually manifest chest pain, syncope, cardiogenic shock, and severe ischemia. LVOTO is easy misdiagnosed as acute coronary syndrome. In our patient, the ECG showed a significant ST-segment depression and a 0/0 mmHg blood pressure when the peak left ventricular outflow tract gradient was abruptly increased by provocable activities. However, the patient had normal coronaries on cardiac catheterization, and, upon being immediately treated with intravenous esmolol, his symptoms were relieved and blood pressure was normal after 30 minutes. This case highlights, not only that early and exact diagnosis of LVOTO is crucial, but also the importance of the therapeutic strategies used.

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Tooth-related inflammatory disorders, including caries, pulpitis, apical periodontitis (AP), and periodontitis (PD), are primarily caused by resident oral microorganisms. Although these dental inflammatory conditions are typically not life-threatening, neglecting them can result in significant complications and greatly reduce an individual's quality of life. Nuclear factor κB (NF-κB), a family formed by various combinations of Rel proteins, is extensively involved in inflammatory diseases and even cancer. This study reviews recent data on NF-κB signaling and its role in dental pulp stem cells (DPSCs), dental pulp fibroblasts (DPFs), odontoblasts, human periodontal ligament cells (hPDLCs), and various experimental animal models. The findings indicate that NF-κB signaling is abnormally activated in caries, pulpitis, AP, and PD, leading to changes in related cellular differentiation. Under specific conditions, NF-κB signaling occasionally interacts with other signaling pathways, affecting inflammation, bone metabolism, and tissue regeneration processes. In summary, data collected over recent years confirm the central role of NF-κB in dental inflammatory diseases, potentially providing new insights for drug development targeting NF-κB signaling pathways in the treatment of these conditions. Keywords: NF-κB, dental caries, pulpitis, apical periodontitis, periodontitis.

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OBJECTIVE: Apical periodontitis (AP) is one of the most common pathologies of the oral cavity. An early and accurate diagnosis of AP lesions is crucial for proper management and planning of endodontic treatments. This study investigated the diagnostic accuracy of periapical radiography (PR) and panoramic radiography (PAN) in the detection of clinically/surgically/histopathologically confirmed AP lesions. METHOD: A systematic literature review was conducted in accordance with the PRISMA guidelines. The search strategy was limited to English language articles via PubMed, Embase and Web of Science databases up to June 30, 2023. Such articles provided diagnostic accuracy values of PR and/or PAN in the detection of AP lesions or alternatively data needed to calculate them. RESULTS: Twelve studies met inclusion criteria and were considered for the analysis. The average value of diagnostic accuracy in assessing AP lesions was 71% for PR and 66% for PAN. According to different accuracy for specific anatomical areas, it is recommended to use PR in the analysis of AP lesions located in the upper arch and lower incisor area, whereas lower premolar and molar areas may be investigated with the same accuracy with PR or PAN. CONCLUSIONS: Two-dimensional imaging must be considered the first-level examination for the diagnosis of AP lesions. PR had an overall slightly higher diagnostic accuracy than PAN. Evidence from this review provided a useful tool to support radiologists and dentists in their decision-making when inflammatory periapical bone lesions are suspected to achieve the best clinical outcome for patients, improving the quality of clinical practice.

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OBJECTIVE: To evaluate the possible effects of apical periodontitis (AP) on cardiac function, structure, and oxidative stress (OS) in rats with diabetes mellitus type 2 (T2DM). DESIGN: Forty-eight (Wistar albino, male) rats were randomized into four groups: control healthy (CTRL), normoglycemic with AP (AP), T2DM, and T2DM with AP (T2DM+AP). T2DM was induced by streptozotocin and a high-fat diet. AP was induced by pulp exposure to the oral environment for 4 weeks and analyzed radiographically. In the blood samples insulin and glucose were established. In vivo, cardiac function was evaluated by echocardiography. Ex vivo cardiac function was assessed by the Langendorff technique. Heart tissue was analyzed pathophysiologically. OS was determined in cardiac tissue homogenate and coronary venous effluent, spectrophotometrically. RESULTS: Impaired glycoregulation was observed in the T2DM+AP group compared to the T2DM, AP, and CTRL groups. The T2DM+AP group was associated with disturbed echocardiography and cardiodynamic parameters. The levels of superoxide anion radical, nitrite, and index of lipid peroxidation were significantly increased, while the superoxide dismutase and catalase were significantly decreased in the T2DM+AP group compared to T2DM, AP, and CTRL groups. The radiographic AP area was significantly larger in the T2DM+AP compared to the AP group. CONCLUSION: AP was associated with increased glucose levels, impaired cardiac function, structure, and OS in diabetic rats. Diabetes was related to an increased radiographic AP area. The study may be a starting point for further research to clarify the effects of AP on cardiac function in various models of systemic diseases.

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AIM: The influence of hypercholesterolemia on the development of apical periodontitis (AP) is inconclusive. Recent studies revealed that cholesterol metabolite 27-hydoxycholesterol (27HC) can affect cellular responses to bacterial infections and oestrogen status and raloxifene may influence its action. Herein, we aimed to examine the impact of 27HC on production of inflammatory mediators by macrophages and the regulatory function of raloxifene. The contribution of 27HC to AP development and the therapeutic effect of raloxifene were evaluated in a rat model. METHODS: Murine macrophages J774 cells were used. The expression of inducible nitric oxide synthase (iNOS) was examined by Western blot. The concentrations of C-C motif chemokine ligand (CCL) 2 and 27HC were assessed by enzyme-linked immunosorbent assay. Colorimetric assay was used to evaluate cholesterol levels. Experimental AP was induced in ovariectomized (OVX) or un-operated rats receiving high-fat/high-cholesterol diet (HFHCD) or normal diet (ND). Micro-computed tomography and immunohistochemistry were employed to evaluate disease severity and the therapeutic effect of raloxifene. RESULTS: Cholesterol enhanced 27HC production in macrophages. 27HC induced iNOS and CCL2 synthesis by macrophages and estradiol suppressed the responses. In our animal model of AP, HFHCD plus OVX significantly augmented serum and lesion tissue levels of 27HC (p < .05 versus the ND group). Lesion size, infiltration of CD68+ cells, and iNOS+ monocytes were increased in parallel with 27HC accumulation. Raloxifene inhibited pro-inflammatory effects of 27HC on macrophages and suppressed AP progression in HFHCD/OVX rats (p < .05 versus the vehicle control group). CONCLUSIONS: Our results suggested that 27HC contributes to AP aggravation associated with hypercholesterolemia. Oestrogen deficiency may both enhance 27HC production and exacerbate its downstream action.

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The body plan of the human parasite Toxoplasma gondii has a well-defined polarity. The minus ends of the 22 cortical microtubules are anchored to the apical polar ring, a putative microtubule-organizing center. The basal complex caps and constricts the parasite posterior end, and is critical for cytokinesis. How this apical-basal polarity is initiated was unknown. Here we examined the development of the apical polar ring and the basal complex using expansion microscopy. We found that substructures in the apical polar ring have different sensitivity to perturbations. In addition, apical-basal differentiation is already established upon nucleation of the cortical microtubule array: arc forms of the apical polar ring and basal complex associate with opposite ends of the microtubules. As the nascent daughter framework grows towards the centrioles, the apical and basal arcs co-develop ahead of the microtubule array. Lastly, two apical polar ring components, APR2 and KinesinA, act synergistically. The removal of individual proteins has modest impact on the lytic cycle. However, the loss of both results in abnormalities in the microtubule array and highly reduced plaquing and invasion efficiency.

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Background Access cavity preparation is a crucial step in nonsurgical root canal treatment. Recent advancements in access cavity designs focus on preserving maximum tooth structure while ensuring sufficient access to canal orifices for effective cleaning and shaping, resulting in minimally invasive procedures. However, there is limited information on the impact of three-dimensional (3D)-guided access cavity preparation in molars. A literature review found no prior studies comparing the effects of various access cavity preparation techniques on apical transportation, untouched surfaces, and debris formation within the canal. Objective The objective of this study is to compare and evaluate the effects of three different access cavity techniques on apical transportation, untouched surfaces, and debris formation within the root canal. Material and methods Thirty extracted permanent mandibular first molars were selected and randomly assigned to three groups for this study: Group I received 3D-printed static guided cavity preparation, Group II underwent conservative access cavity preparation, and Group III was subjected to traditional access cavity (TAC) preparation. The mesial canals in all samples were cleaned and shaped using TruNatomy files. Preoperative and postoperative micro-CT imaging was performed on each sample to assess the effects of the different access cavity preparation techniques on apical transportation, untouched surfaces, and debris formation within the root canal. Results The study found that Group I, which used 3D-printed static guided cavity preparation, exhibited significantly less apical transportation compared to Groups II and III, with mean differences of -0.1677 and -0.2079, respectively. Debris accumulation was similar across all groups, with mean values of 0.928 ± 0.824 for Group I, 0.751 ± 0.495 for Group II, and 0.938 ± 0.681 for Group III, indicating no significant impact of cavity preparation type on debris levels. For untouched canal surfaces, Group III (TAC preparation) had the fewest untouched surfaces, with mean differences of 3.0380 and 3.9020 compared to Groups II and I, respectively. Conclusions While TAC preparation reduces substantial tooth structure, it shows higher instrumentation efficacy and better cleaning of the root canal system. However, in complex cases where tooth structure preservation is crucial, guided access cavity preparation provides an effective balance between structural conservation and adequate canal access. This approach offers a tailored solution, optimizing treatment outcomes based on the specific clinical scenario.

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BACKGROUND: Apical hypertrophic cardiomyopathy (ApHCM) is a unique disease with pathological hypertrophy mainly at the left ventricular (LV) apex. Although previous studies have indicated apical dysfunction in ApHCM, how apical mechanics change during disease progression has not been thoroughly examined. We aimed to characterize the mechanics of the LV apex in ApHCM patients at different disease stages and explore the clinical significance of these alterations. METHODS: 104 ApHCM patients were divided into 3 subtypes based on LV apical maximum wall thickness (AMWT) and extent of hypertrophy: relative-type (isolated apical hypertrophy with AMWT <15 mm), pure-type (isolated apical hypertrophy with AMWT ≥15 mm), and mixed-type (both apical and midventricular hypertrophy with AMWT ≥15 mm). Two-dimensional speckle-tracking echocardiography was used to analyze LV segmental strain, global strain, and twist. Comparisons of these parameters were performed among ApHCM subtypes and 30 healthy controls. Logistic regression and Cox proportional hazard regression analyses were employed to explore associations between myocardial mechanics and clinical indicators. A composite outcome of new-onset atrial fibrillation, heart failure hospitalization, myectomy, and all-cause mortality was assessed. RESULTS: Even in relative ApHCM patients, apical longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) were significantly impaired compared to controls (LS: -14.6±4.1% vs.-20.0±1.7%, p=0.001; CS: -19.6±2.5% vs.-25.6±3.7%, p=0.002; RS: 26.6±7.4% vs. 35.6±11.1%, p=0.026), while apical rotation and LV twist remained unchanged. In patients with greater apical hypertrophy (mixed and pure patients), apical LS and RS were more abnormal. Moreover, apical rotation showed significant reductions compared to relative-type patients. After adjusting for clinical and myocardial mechanical parameters, apical rotation was independently associated with NYHA class ≥ II (odds ratio =0.81, 95% confidence interval [CI]: 0.66-0.99, p=0.036) and the composite outcome (hazard ratio =0.82, 95% CI: 0.73-0.91, p=0.001). CONCLUSIONS: Relative ApHCM demonstrates apical dysfunction but sparing of apical rotation, which was abnormal in more extensive phenotypes. LV apex mechanics were closely related to clinical patterns, with apical rotation correlated with both NYHA class ≥ II and clinical events.

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The successful outcome of endodontic treatment is dependent on the immune response and the reparative potential of the individual. Alteration in the host immune response is a common characteristic shared by both apical periodontitis and systemic diseases. Although infection-induced periapical lesions occur in a localized environment, numerous epidemiologic studies in the last few decades have investigated the potential association between endodontic disease pathogenesis and systemic diseases. The goal of this review is to identify common systematic factors and discuss the effect they may or may not have on the prognosis and outcome of endodontic therapy.

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Endodontic and periodontal disease are distinct etiologies that can lead to odontogenic sinusitis (ODS). Apical periodontitis and periodontitis are both polymicrobial infections but with different pathogens affecting different parts of the tooth and alveolar bone. Diagnosing both conditions requires specific clinical examination in addition to radiographic assessment. Understanding the terminology and pathophysiology of these conditions and how they are identified should improve diagnostic and therapeutic outcomes, as well as future ODS research.

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BACKGROUND: Regenerative endodontic procedures (REPs) is effective for treating young permanent teeth with pulp necrosis. However, its efficacy on delayed replanted avulsed teeth is unclear. AIM: This retrospective study aimed to assess the efficacy of REPs in treating delayed replanted immature permanent teeth with apical periodontitis. DESIGN: Avulsed teeth receiving REPs were systematically screened based on predetermined criteria. This study assessed the REP outcomes, postoperative periodontal healing, and overall treatment efficacy. Samples were grouped by REP outcomes and root development stage, with Fisher's exact tests used to compare outcomes among different groups. RESULTS: Among the included 17 teeth, 47.1% exhibited successful REPs and periodontal healing. Another 47.1%, due to replacement resorption or REP failure, were categorized as tooth survival. Healing of periapical lesions was observed in 88.2% of the cases, but only 41.2% demonstrated continued root development. Although differences were not significant (p = 0.05), teeth with continued root development had a higher rate of functional healing (85.7%) compared to those without (30%). CONCLUSION: Within the limitations of this study, REPs presented reliable outcomes for treating delayed replanted immature permanent teeth with apical periodontitis mainly in periapical lesion healing. Teeth with continued root development after REPs exhibited a higher rate of functional healing. Further investigation is required to explore potential synergies between REP outcomes and periodontal healing.

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Takotsubo syndrome is a condition characterised by temporary acute left ventricular dysfunction with regional wall abnormalities extending beyond a single coronary artery territory. Initially thought to be benign, this condition, which is challenging to distinguish from acute coronary syndrome, has substantial morbidity and mortality. The mechanism behind this condition remains elusive, but multiple theories have been proposed. Although beta blockers and angiotensin-converting enzyme inhibitors are used as treatments for left ventricular dysfunction, currently, there are no randomised controlled trials to support their use. In this paper, we review the latest evidence regarding aetiologies, pathophysiology, diagnostic criteria, prognosis, complications and management of Takotsubo syndrome.

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BACKGROUND: Root canal retreatment is necessary when initial treatment fails. Nickel-titanium systems help remove filling materials; however, some methods can cause canal content extrusion, resulting in inflammation and delayed healing. This study aimed to examine the impact of different preparation techniques and endodontic file systems on apical debris volume to limit material dispersion to periradicular tissues. METHODS: Ninety extracted maxillary incisors were evaluated. Simulated apical root resorption was created by removing the apical 2 mm of the root. The teeth were divided into two groups: one filled with a single cone and the other with cold lateral compaction (CLC). Each group was further divided into three subgroups (n = 15 each): Subgroup 1 used Reciproc R25 for removal and R50 for final preparation; Subgroup 2 used ProTaper Universal Retreatment (PTUR) files D1, D2, and D3 for removal and ProTaper Next X5 for finalization; and Subgroup 3 used VDW.Rotate Retreatment (VDW.RotateR) for removal and VDW.Rotate 50.04 for completion. Debris from retreatment was collected in pre-weighed tubes to determine the amount. The apical extrusion data underwent a two-way analysis of variance. RESULTS: The Reciproc group had a mean extruded debris weight of 0.54 ± 0.24 mg, higher than the PTUR (0.28 ± 0.15 mg) and VDW.RotateR (0.39 ± 0.29 mg) groups (p < 0.05). The single-cone technique (SCT) resulted in a mean debris weight of 0.34 ± 0.23 mg, lower than the CLC technique, which had a mean of 0.46 ± 0.27 mg (p < 0.05). SCT had a shorter retreatment duration (111.12 ± 33.46 s) compared to CLC (176.26 ± 52.26 s) (p < 0.05). CONCLUSION: The Reciproc file system and the CLC obturation technique resulted in greater apical debris extrusion than the other methods. SCT was quicker than CLC. The Reciproc groups are more susceptible to apex extrusion during retreatment.

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Apical periodontitis (AP) is the most prevalent chronic inflammatory disease of the teeth. Bone resorption dynamics in symptomatic and asymptomatic AP are still unrecognized. This study examined different inflammatory markers within gingival crevicular fluid, including matrix metalloproteinases 8 (MMP8), tissue inhibitors of metalloproteinases 1 (TIMP1), receptor activator of nuclear factor κB (RANK), its ligand (RANKL), and osteoprotegerin (OPG), to be used in comparing symptomatic apical periodontitis (SAP) and asymptomatic apical periodontitis (AAP) versus healthy teeth. Subjects with SAP, AAP, and a control group were recruited and GCF samples were collected by Periopaper strips. Clinical and radiographical measures were used for diagnosing AP. Levels of MMP8, TIMP, RANK, RANKL, and OPG were determined by ELISA and their abilities to discriminate between examined sites were evaluated by receiver operator characteristic (ROC) curves. All examined biomarkers were statistically significant higher (p < 0.05) in SAP than AAP and the control group, apart from RANK. Significant positive correlations (p < 0.05) were identified between all SAP and AAP biomarkers except TIMP1 and RANK in AAP teeth. TIMP1 and OPG exhibited the highest ability to distinguish between SAP and AAP with areas under the curve of 0.824 and 0.763 in comparing SAP and the control group, and 0.732 and 0.73 when comparing AAP and the control group, respectively. Additionally, TIMP1 and OPG showed the highest AUC of 0.778 and 0.747 when SAP and AAP were compared, respectively. This study concluded that GCF levels of TIMP1 and OPG can be used to differentiate between SAP, AAP, and healthy teeth.

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Cardiac amyloidosis is an infiltrative disease that causes progressive myocardial impairment secondary to amyloid fibril deposition in the extracellular space of the myocardium. Many amyloid precursors, including transthyretin protein, are known to determine cardiac damage by aggregating and precipitating in cardiac tissue. Transthyretin cardiac amyloidosis may be either caused by rare genetic mutations of the transthyretin gene in the hereditary variant, or may arise as a consequence of age-related mechanisms in the acquired form. Although it has been labeled as a rare disease, in recent years, transthyretin cardiac amyloidosis has stood out as an emerging cause of aortic stenosis, unexplained left ventricular hypertrophy and heart failure with preserved ejection fraction, particularly in the elderly. Indeed, the integration of data deriving from both in vivo imaging techniques (whose advancement in the last years has allowed to achieve an easier and more accessible non-invasive diagnosis) and forensic studies (showing a prevalence of amyloid deposition in cardiac tissue of elderly patients up to 29%) suggests that cardiac amyloidosis is a more common disease than traditionally considered. Thanks to all the improvements in non-invasive diagnostic techniques, along with the development of efficacious therapies offering improvements in survival rates, transthyretin cardiac amyloidosis has been transformed from an incurable and infrequent condition to a relatively more diffuse and treatable disease, which physicians should take into consideration in the differential diagnostic processes in daily clinical practice.

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Background: Determining the correct apical limit for root canal treatment is essential for its success. This study evaluates the accuracy of three electronic apex locators (EALs) in locating the apical constriction (AC) in molar canals. Methods: Forty extracted human mandibular molars were scanned using micro-CT, and endodontic access cavities were created. Teeth were mounted in alginate, and three EALs-Root ZX-mini, Root ZX-II, and Sirona integrated apex locator-were used to measure the canal working length in dry canals and with EDTA gel. Micro-CT scans were performed with files in place, and the distance from the AC was calculated. Measurements within 0.1-0.5 mm were categorized as 'close'. Those extending beyond towards the major foramen were categorized as 'beyond', otherwise they were classified as 'far'. Data analysis was conducted with a level of significance set at 5%. Results: Most readings for all EALs were in the 'close' category, with significant differences between devices (p < 0.0001). Root ZX-mini and Root ZX-II had 74.4% and 72.5% 'close' readings, respectively, versus 51% for Sirona integrated. Accuracy did not differ significantly between dry and EDTA-treated canals (p = 0.306). All EALs demonstrated excellent operator reliability (ICC 0.996-1.00). Conclusions: All EALs accurately determined AC, unaffected by lubricants. However, Root ZX-mini and Root ZX-II outperformed Sirona integrated. All EALs showed consistent reliability.

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INTRODUCTION: Hepcidin, a central regulatory molecule of iron metabolism, is upregulated through the IL-6/STAT3 signaling pathway in inflammatory and infectious states, contributing to the pathogenesis of various diseases. In chronic apical periodontitis (CAP), Porphyromonas gingivalis (P. gingivalis) and its lipopolysaccharides (LPS) activate various immune responses in vivo, contributing to disease progression. This study evaluated the role and mechanism of hepcidin in P. gingivalis-induced bone tissue damage in CAP, focusing on its promotion of macrophage M1 polarization via the IL-6/STAT3 signaling pathway. METHODS: We analyzed a GSE77459 dataset from the GEO database, containing data from inflammatory and normal dental pulp tissues. RT-qPCR and immunofluorescence staining were used to detect the expression of hepcidin in human CAP tissues and its relationship with macrophages. Mouse bone marrow derived macrophages (BMDMs) were cultured in vitro and stimulated with P. gingivalis LPS. The effects of Stattic on macrophage hepcidin expression, IL-6 expression, STAT3 phosphorylation, and macrophage polarization were detected by ELISA, western blotting, RT-qPCR, and flow cytometry, respectively. RESULTS: Hepcidin expression in human inflammatory dental pulp tissues was upregulated via the IL-6/STAT3 pathway and correlated with macrophage polarization. Hepcidin-encoding genes were found to be highly expressed and primarily associated with M1 macrophages in CAP tissues. In vitro experiments revealed that P. gingivalis LPS stimulation induced macrophages to express hepcidin through the IL-6/STAT3 pathway and polarize to M1. Additionally, the IL-6/STAT3 pathway inhibitor Stattic suppressed these changes. CONCLUSIONS: Our study demonstrates that in CAP, macrophages highly express hepcidin, which subsequently alters macrophage metabolism, regulates M1 polarization, and leads to bone tissue destruction.

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BACKGROUND AND OBJECTIVES: The aim of this study is to establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy in the context of stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: Individual patient data from 349 patients with 356 apical lung malignancies who underwent SBRT were extracted from 5 articles. The anatomical brachial plexus was delineated following the guidelines provided in the atlases developed by Hall, et al. and Kong, et al.. Patient characteristics, pertinent SBRT dosimetric parameters, and brachial plexopathy grades (according to CTCAE 4.0 or 5.0) were obtained. Normal tissue complication probability (NTCP) models were used to estimate the risk of developing grade ≥ 2 brachial plexopathy through maximum likelihood parameter fitting. RESULTS: The prescription dose/fractionation schedules for SBRT ranged from 27 to 60 Gy in 1 to 8 fractions. During a follow-up period spanning from 6 to 113 months, 22 patients (6.3 %) developed grade ≥2 brachial plexopathy (4.3 % grade 2, 2.0 % grade 3); the median time to symptoms onset after SBRT was 8 months (ranged, 3-54 months). NTCP models estimated a 10 % risk of grade ≥2 brachial plexopathy with an anatomic brachial plexus maximum dose (Dmax) of 20.7 Gy, 34.2 Gy, and 42.7 Gy in one, three, and five fractions, respectively. Similarly, the NTCP model estimates the risks of grade ≥2 brachial plexopathy as 10 % for BED Dmax at 192.3 Gy and EQD2 Dmax at 115.4 Gy with an α/ß ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %). CONCLUSIONS: This study establishes dosimetric constraints ranging from 20.7 to 42.7 Gy across 1-5 fractions, aimed at mitigating the risk of developing grade ≥2 brachial plexopathy following SBRT. These findings provide valuable guidance for future ablative SBRT in apical lung malignancies.

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BACKGROUND: Apical hypertrophic cardiomyopathy (ApHCM) is a variant of hypertrophic cardiomyopathy, with distinct clinical characteristics and outcomes. We aimed to clarify the natural history of patients with ApHCM and identify the risk of end-stage heart failure incidence. METHODS AND RESULTS: This retrospective study was conducted on patients with hypertrophic cardiomyopathy in China between January 2009 and February 2024. Patients were stratified into ApHCM and non-ApHCM groups. The primary outcome was a composite of major adverse cardiovascular events, including all-cause deaths, heart failure hospitalization, sudden cardiac death, and ventricular tachycardia. The secondary outcome was the incidence of end-stage heart failure, defined as left ventricular ejection fraction <50%. Kaplan-Meier and univariable and multivariable Cox proportional analyses were applied. Adjustment variables were included for important baseline characteristics, comorbidities, and medication use. Of 5653 patients enrolled with hypertrophic cardiomyopathy, 584 (10.3%) had ApHCM and 5069 (89.7%) had non-ApHCM. During the median follow-up period of 4.6 years (1.6-8.0 years), major adverse cardiovascular events occurred in 32.2% (n=1808), with a lower incidence in patients with ApHCM than non-ApHCM (20.4% versus 33.3%, P<0.001). Non-ApHCM was an independent predictor of major adverse cardiovascular events (hazard ratio [HR], 1.65 [95% CI, 1.36-1.99]; P<0.001). In the serial cohort, patients with ApHCM exhibited a lower incidence of end-stage heart failure than those with non-ApHCM (12.4% versus 2.7%, P<0.001). Non-ApHCM was associated with a higher risk of end-stage heart failure development (HR, 2.31 [95% CI, 1.28-4.15]; P<0.001). In subgroup and sensitivity analysis, the results were consistent for our main and secondary outcomes. CONCLUSIONS: ApHCM is relatively common in hypertrophic cardiomyopathy and shows lower rates of all-cause mortality and heart failure hospitalizations than non-ApHCM.