Extracellular Vesicle DNA Extraction and Sequencing in Ancient Serum Samples From Patients With Breast Cancer.

BACKGROUND/AIM: Extracellular vesicle DNA (EV-DNA) has emerged as a novel biomarker for tumor mutation detection using liquid biopsies, exhibiting biological advantages compared to cell-free DNA (cfDNA). This study assessed the feasibility of EV-DNA and cfDNA extraction and sequencing in old serum samples of patients with breast cancer (BC). PATIENTS AND METHODS: A total of 28 serum samples of 27 patients with corresponding clinical information were collected between 1983 and 1991. EV-DNA was extracted using Exo-GAG kit (Nasabiotech) and cfDNA using QIAsymphony DSP Virus/Pathogen Midi Kit (Qiagen), respectively. Subsequently, 10 matched samples (EV-DNA n=5, cfDNA n=5) of five patients were subjected to sequencing using the Oncomine™ Breast cfDNA Research Assay v2 (Thermo Fisher Scientific). RESULTS: Samples were collected on median 1.9 years after primary diagnosis [interquartile range (IQR)=0.2-7.2]. Median follow-up was 9.5 years (IQR=5.2-14.2). Median age of serum samples was 36.1 years (IQR=34.5-37.3). EV-DNA and cfDNA were extracted from 100% (28/28) of the included samples. Both, DNA quantity and concentration were comparable between EV-DNA and cfDNA. Sequencing was successfully performed in 100% (10/10) of the included samples. Two matched analyses yielded equivalent results in EV-DNA and cfDNA (no mutations, n=1; PIK3CA mutation, n=1), whilst in two analyses, PIK3CA mutation was only found in cfDNA, and in one analysis, a TP53 mutation was only found in EV-DNA. CONCLUSION: EV-DNA extraction and sequencing in old serum samples of patients with BC is feasible and has the potential to address clinically relevant questions in longitudinal studies.

Spatially distributed atmospheric boundary layer properties in Houston - A value-added observational dataset.

In 2022, Houston, TX became a nexus for field campaigns aiming to further our understanding of the feedbacks between convective clouds, aerosols and atmospheric boundary layer (ABL) properties. Houston's proximity to the Gulf of Mexico and Galveston Bay motivated the collection of spatially distributed observations to disentangle coastal and urban processes. This paper presents a value-added ABL dataset derived from observations collected by eight research teams over 46 days between 2 June - 18 September 2022. The dataset spans 14 sites distributed within a ~80-km radius around Houston. Measurements from three types of instruments are analyzed to objectively provide estimates of nine ABL parameters, both thermodynamic (potential temperature, and relative humidity profiles and thermodynamic ABL depth) and dynamic (horizontal wind speed and direction, mean vertical velocity, updraft and downdraft speed profiles, and dynamical ABL depth). Contextual information about cloud occurrence is also provided. The dataset is prepared on a uniform time-height grid of 1 h and 30 m resolution to facilitate its use as a benchmark for forthcoming numerical simulations and the fundamental study of atmospheric processes.

Personalizing Locoregional Therapy in Patients With Breast Cancer in 2024: Tailoring Axillary Surgery, Escalating Lymphatic Surgery, and Implementing Evidence-Based Hypofractionated Radiotherapy.

The management of axillary lymph nodes in breast cancer is continually evolving. Recent data now support omitting axillary lymph node dissection (ALND) in most patients with metastases in up to two sentinel lymph nodes (SLNs) during upfront surgery and those with residual isolated tumor cells after neoadjuvant chemotherapy (NACT). In the upfront surgery setting, ALND is still indicated, however, in patients with clinically node-positive breast cancer or more than two positive SLNs and, after NACT, in case of residual micrometastases and macrometastases. Omission of the sentinel lymph node biopsy (SLNB) can be considered in many postmenopausal patients with small luminal breast cancer, particularly when axillary ultrasound is negative. Several randomized controlled trials (RCTs) are currently aiming at eliminating the remaining indications for ALND and also establishing omission of SLNB in a broader patient population. The movement to deescalate axillary staging is in part because of the association between ALND and lymphedema, which is swelling of an extremity because of lymphatic damage and obstructed lymphatic drainage. To reduce the risk of developing this condition, patients undergoing ALND can undergo reverse mapping of the axilla and immediate reconstruction or bypass of the lymphatics from the involved extremity. Decongestion and compression are the foundation of conservative treatment for established lymphedema, while lymphovenous bypass and lymph node transfer are surgical procedures to address the physiologic dysfunction. Radiotherapy is an essential component of breast locoregional therapy: more than three decades of radiation research has optimized treatment according to patient's risk of local recurrence while substantially reducing the number of treatment visits. High-quality RCTs have shown the efficacy and safety of hypofractionation-more than 2Gy radiation dose per treatment (fraction)-significantly reducing the burden of radiotherapy treatment for many patients with breast cancer. In 2024, guidelines recommend no more than 15-16 fractions for whole-breast and nodal radiotherapy, with some recommending five fractions for whole-breast radiotherapy. In addition, simultaneous integrated boost (SIB) has been shown to be noninferior to sequential boost with regards to ipsilateral breast tumor recurrence with similar or reduced long-term side effects, also reducing overall treatment length. Further RCTs are underway investigating other indications for five fractions, including SIB and regional node irradiation, such that, in future, it may be possible for the majority of breast radiotherapy patients to be treated with a 1-week course. This manuscript serves to outline the latest updates on axillary surgical staging, lymphatic surgery, and evidence-based radiotherapy in the treatment of breast cancer.

Prognostic Importance of Axillary Lymph Node Response to Neoadjuvant Systemic Therapy on Axillary Surgery in Breast Cancer-A Single Center Experience.

Neoadjuvant systemic treatment (NST) is the standard treatment for HER2+, triple-negative (TN), and highly proliferative luminal HER2- early breast cancer. Pathologic complete response (pCR) after NST is associated with improved outcomes. We evaluated the predictive factors for axillary-pCR (AXpCR) and its impact on the extent of axillary node surgery. This retrospective study included 92 patients (median age of 50.4 years) with an initially node-positive disease. Patients were treated with molecular subtype-specific NST (4.3% were luminal A-like, 28.3% luminal HER2-, 26.1% luminal HER2+, 18.5% HER2+ non-luminal, and 22.8% TN). Axillary-, breast- and total-pCR were achieved in 52.2%, 48.9%, and 38% of patients, respectively. In a binary logistic regression model for the whole population, the only independent factor significantly associated with AXpCR was breast-pCR (OR 7.4; 95% CI 2.6-20.9; p < 0.001). In patients who achieved breast-pCR, aggressive subtypes (HER2+ and TN; OR 11.24) and clinical tumor stage (OR 0.10) had a significant impact on achieving AXpCR. Axillary lymph node dissection was avoided in 53.3% of patients. In conclusion, in node-positive patients with HER2+ and TN subtypes, who achieved breast-pCR after NST, de-escalation of axillary surgery could be considered in most cases.

[Impact of the Reflux Origin on the Clinical Stage and Surgical Decision in Primary Varicose Veins]. / Einfluss des Refluxursprungs auf die Hämodynamik, Klinik und Therapie der primären Varikose.

Reflux and recirculation in primary varicose veins are not yet completely understood, and the contribution of perforator veins is dual.Reflux origin was assessed as junctional (JP, reflux of the greater saphenous junction or groin recurrences) with/without suspect perforator veins (SPV), or perforator phenotype (PP, reflux from SPV only or for statistical purposes from the small saphenous vein). Flow direction and intensity were recorded under Valsalva (JP) or as spontaneous/under distal compression/decompression (SPV) and weighted with one/two points as reflux/reentry, respectively, in the case of SPV. We compared the origin and extent of axial reflux and diameter/flow direction of SPV with the clinical stage by multivariate analysis.Of 107 limbs, 68 presented with JP, 49 combined with SPV, and 39 with PP. CEAP C3-C6 was associated with the presence of SPV (JP and PP) in 45/65 (11/22) limbs with primaries (recurrences) or in 3/16 (0/4), p < 0.01 (p = 0.01), without SPV. C4-C6 at first manifestation, however, was more frequent in JP and axial reflux below the knee in 14/39 limbs (p = 0.01) or above the knee in 3/11 (p = 0.12) compared with PP (5/31). SPV flow at first manifestation was reentry in the case of JP and axial reflux below the knee (estimate -1.62, p = 0.02) or above the knee (0.29, p = 0.81) compared with PP, but diameter of the most dilated perforator vein was higher in the case of JP and axial reflux above the knee (estimate 0.20, p < 0.01) or below the knee (0.04, p = 0.30) compared with PP. Predominant SPV flow was reentry/reflux during peripheral compression/decompression, respectively (p = 0.009).The data suggest that the reflux origin and extent of axial reflux are associated with diameter/flow direction of SPV and clinical stage in primary varicose veins.

Using ChatGPT-Like Solutions to Bridge the Communication Gap Between Patients With Rheumatoid Arthritis and Health Care Professionals.

The communication gap between patients and health care professionals has led to increased disputes and resource waste in the medical domain. The development of artificial intelligence and other technologies brings new possibilities to solve this problem. This viewpoint paper proposes a new relationship between patients and health care professionals-"shared decision-making"-allowing both sides to obtain a deeper understanding of the disease and reach a consensus during diagnosis and treatment. Then, this paper discusses the important impact of ChatGPT-like solutions in treating rheumatoid arthritis using methotrexate from clinical and patient perspectives. For clinical professionals, ChatGPT-like solutions could provide support in disease diagnosis, treatment, and clinical trials, but attention should be paid to privacy, confidentiality, and regulatory norms. For patients, ChatGPT-like solutions allow easy access to massive amounts of information; however, the information should be carefully managed to ensure safe and effective care. To ensure the effective application of ChatGPT-like solutions in improving the relationship between patients and health care professionals, it is essential to establish a comprehensive database and provide legal, ethical, and other support. Above all, ChatGPT-like solutions could benefit patients and health care professionals if they ensure evidence-based solutions and data protection and collaborate with regulatory authorities and regulatory evolution.

[New treatment options in system therapy for breast carcinoma and associated new side effects].

INTRODUCTION: Breast cancer today has a significantly better prognosis than two to three decades ago. Treatment options have improved significantly. However, new systemic therapy has also resulted in side effects that clinicians must first become familiar with in order to be able to treat them optimally. This article gives an overview of the most important innovations in the last 10 years in the field of systemic therapy in breast cancer and also shows the most important side effects and their management.

Unexpectedly rapid aerosol formation in the Hunga Tonga plume.

The Hunga Tonga-Hunga Ha'apai (HT-HH) volcanic eruptions on January 13 and 15, 2022, produced a plume with the highest signal in stratospheric aerosol optical depth observed since the eruption of Mt. Pinatubo in 1991. Suites of balloon-borne instruments on a series of launches from Réunion Island intercepted the HT-HH plume between 7 and 10 d of the eruptions, yielding observations of the aerosol number and size distribution and sulfur dioxide (SO2) and water vapor (H2O) concentrations. The measurements reveal an unexpected abundance of large particles in the plume, constrain the total sulfur injected to approximately 0.2 Tg, provide information on the altitude of the injection, and indicate that the formation of sulfuric acid aerosol was complete within 3 wk. Large H2O enhancements contributed as much as ~30% to ambient aerosol surface area and likely accelerated SO2 oxidation and aerosol formation rates in the plume to approximately three times faster than under normal stratospheric conditions.

Rapid ozone depletion after humidification of the stratosphere by the Hunga Tonga Eruption.

The eruption of the Hunga Tonga-Hunga Ha'apai volcano on 15 January 2022 offered a good opportunity to explore the early impacts of tropical volcanic eruptions on stratospheric composition. Balloon-borne observations near Réunion Island revealed the unprecedented amount of water vapor injected by the volcano. The enhanced stratospheric humidity, radiative cooling, and expanded aerosol surface area in the volcanic plume created the ideal conditions for swift ozone depletion of 5% in the tropical stratosphere in just 1 week. The decrease in hydrogen chloride by 0.4 parts per million by volume (ppbv) and the increase in chlorine monoxide by 0.4 ppbv provided compelling evidence for chlorine activation within the volcanic plume. This study enhances our understanding of the effect of this unusual volcanic eruption on stratospheric chemistry and provides insights into possible chemistry changes that may occur in a changing climate.

A Giant Posterior Maxillary Intra-Sinusal Complex Odontoma: A Clinical Case.

Odontomas are the most common odontogenic neoplasms. They are generally small and asymptomatic. This article presents an unusual case of a giant maxillary complex odontoma, which obscured a part of the maxillary antrum and impacted a tooth. This was discovered during an episode of maxillofacial cellulitis. In this case, surgical excision of the lesion was performed under general anesthesia, and the closure was performed with a fat pad pedicled flap. A brief review of the literature was performed to analyze the characteristics of this clinical entity and their implication in the treatment.

The Lucerne Toolbox 2 to optimise axillary management for early breast cancer: a multidisciplinary expert consensus.

Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the "Lucerne Toolbox", a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients' journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%-74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema.

Understanding ozone episodes during the TRACER-AQ campaign in Houston, Texas: The role of transport and ozone production sensitivity to precursors.

This study investigated transport pathways and photochemical formation responsible for ozone exceedances during the September 2021 deployment of the Tracking Aerosol Convection Interactions ExpeRiment/Air Quality (TRACER-AQ) campaign in Houston, Texas. We focused on two ozone episodes, September 6th-September 11th ("Episode 1") and September 23rd-September 26th ("Episode 2"), when the maximum daily eight-hour average (MDA8) ozone at surface monitors exceeded 70 ppbv. Long-range transport patterns of air masses during these episodes were from the central/northern US. High-resolution (4 km resolution) trajectory analysis with FLEXible PARTicle (FLEXPART) dispersion model revealed local recirculation of air masses and the accumulation of pollutants across Houston contribute to the ozone exceedances. Comprehensive Air Quality Model with extensions (CAMx) driven by 1.33-km resolution meteorology from the Weather Research and Forecast (WRF) tool simulated elevated ozone production rates during ozone episodes across the Houston metropolitan area, with ozone production hotspots mostly over Houston city and industrial districts of the Houston Ship Channel (HSC). The regional increase in ozone production rates was due to the transport of VOC-rich air masses (via northerly flows) that brought ozone precursors to the region, which ultimately caused a transition in the ozone formation tendency from generally VOC-limited to NOx-limited conditions. However, the city of Houston and the HSC remained in a VOC-limited regime because of local NOx emissions that, to some extent, preponderated the impact of transported VOCs. While approximately 37 % of the elevated ozone production was attributed to local photochemistry, the remaining ∼63 % increase in ozone production was due to the transported ozone to the region during episodes, bringing ozone to the Houston region and contributing to ozone exceedances. The outcomes of this study illustrated the synergy between transport and ozone production, both long-range and local scale, which resulted in ozone exceedances in Houston.

Localization Techniques for Non-Palpable Breast Lesions: Current Status, Knowledge Gaps, and Rationale for the MELODY Study (EUBREAST-4/iBRA-NET, NCT 05559411).

BACKGROUND: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. METHODS: We performed a systematic review on localization techniques for non-palpable breast cancer. RESULTS: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons' and radiologists' attitudes towards these techniques. CONCLUSIONS: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.

Soil-plant interactions modulated water availability of Swiss forests during the 2015 and 2018 droughts.

Central Europe has been experiencing unprecedented droughts during the last decades, stressing the decrease in tree water availability. However, the assessment of physiological drought stress is challenging, and feedback between soil and vegetation is often omitted because of scarce belowground data. Here we aimed to model Swiss forests' water availability during the 2015 and 2018 droughts by implementing the mechanistic soil-vegetation-atmosphere-transport (SVAT) model LWF-Brook90 taking advantage of regionalized depth-resolved soil information. We calibrated the model against soil matric potential data measured from 2014 to 2018 at 44 sites along a Swiss climatic and edaphic drought gradient. Swiss forest soils' storage capacity of plant-available water ranged from 53 mm to 341 mm, with a median of 137 ± 42 mm down to the mean potential rooting depth of 1.2 m. Topsoil was the primary water source. However, trees switched to deeper soil water sources during drought. This effect was less pronounced for coniferous trees with a shallower rooting system than for deciduous trees, which resulted in a higher reduction of actual transpiration (transpiration deficit) in coniferous trees. Across Switzerland, forest trees reduced the transpiration by 23% (compared to potential transpiration) in 2015 and 2018, maintaining annual actual transpiration comparable to other years. Together with lower evaporative fluxes, the Swiss forests did not amplify the blue water deficit. The 2018 drought, characterized by a higher and more persistent transpiration deficit than in 2015, triggered widespread early wilting across Swiss forests that was better predicted by the SVAT-derived mean soil matric potential in the rooting zone than by climatic predictors. Such feedback-driven quantification of ecosystem water fluxes in the soil-plant-atmosphere continuum will be crucial to predicting physiological drought stress under future climate extremes.

The forgotten node: Axillary surgery mandates expertise.

The therapeutic role of axillary dissection in breast cancer is gradually abandoned. However, in some cases axillary dissection is still indicated, and this mandates expertise in planning the operation according to imaging, understanding of current methods of axillary marking, and expertise in performing a more radical resection. In this comment we describe cases of gross nodal disease that was left behind at the time of axillary dissection and was later noted on a radiation planning CT.

The metastatic spread of breast cancer accelerates during sleep.

The metastatic spread of cancer is achieved by the haematogenous dissemination of circulating tumour cells (CTCs). Generally, however, the temporal dynamics that dictate the generation of metastasis-competent CTCs are largely uncharacterized, and it is often assumed that CTCs are constantly shed from growing tumours or are shed as a consequence of mechanical insults1. Here we observe a striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and mouse models, highlighting that most spontaneous CTC intravasation events occur during sleep. Further, we demonstrate that rest-phase CTCs are highly prone to metastasize, whereas CTCs generated during the active phase are devoid of metastatic ability. Mechanistically, single-cell RNA sequencing analysis of CTCs reveals a marked upregulation of mitotic genes exclusively during the rest phase in both patients and mouse models, enabling metastasis proficiency. Systemically, we find that key circadian rhythm hormones such as melatonin, testosterone and glucocorticoids dictate CTC generation dynamics, and as a consequence, that insulin directly promotes tumour cell proliferation in vivo, yet in a time-dependent manner. Thus, the spontaneous generation of CTCs with a high proclivity to metastasize does not occur continuously, but it is concentrated within the rest phase of the affected individual, providing a new rationale for time-controlled interrogation and treatment of metastasis-prone cancers.

Case report of a zygomatic bone hemangioma surgery with reconstruction by a custom-made implant.

Intraosseous hemangiomas are rare tumors. A 43-year-old woman was referred with a mass in the right zygomatic bone, showing a slow volume increase and pain symptomatology. A surgical management with bone reconstruction using a custom-made implant was decided. Historically, various autografts and alloplastic materials have been used for this type of bone loss. The use of custom-made biomaterials opens new possibilities in maxillofacial reconstructive surgery. The patient showed no symptoms postoperatively and her zygomatic bones were symmetrized. For the authors, this approach seems to be a reliable and reproducible method for zygomatic bone reconstructions.

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy.

AIM: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. METHODS: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. RESULTS: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. CONCLUSIONS: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR.