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The African baobab, Adansonia digitata L., has great paleoclimatological potential because of its wide distributional range and millennial length life span. However, dendroclimatological approaches are hampered by dating uncertainties due to its unique, parenchyma-dominated stem anatomy. Here, securely dated time series of annual wood increment growth and intra-ring stable isotopes of carbon and oxygen of cellulose for a baobab tree from Oman covering 1941 to 2005 were established and tested for relationships to hydroclimate variability. Precise dating with the atomic bomb peak (ABP) using highly resolved 14C measurements confirmed the annual character of the baobab's growth rings. F14C values of tree-ring cellulose were found up to 8.8 % lower than in the corresponding atmospheric CO2 for the period around the ABP, which in conjunction with a considerable autocorrelation of the δ13C series points to the incorporation of previous year's carbon contributing to the average age of intra-ring wood samples. F14C of terminal parenchyma bands, marking the tree-ring boundaries, were found to be considerably younger than their corresponding tree ring, indicating that parenchyma tissue is alive for many years, probably undergoing cell division and structural reorganization and contributing to secondary growth. In contrast to the δ13C time series, no significant autocorrelation was found in the δ18O series of tree-ring cellulose despite the enormous water storage potential of this stem-succulent tree species. Year-to-year variability in tree-ring width and stable isotope ratios revealed radial stem growth and the geochemistry of wood cellulose are influenced by fluctuations in the hydroclimate. In particular, δ18O was found to be a good climate proxy, followed by tree-ring width and δ13C. Tree-ring width and intra-ring δ18Omin correlated well with each other and with precipitation amount for the period from pre-monsoon May to the end of the monsoon season in September/October. Intra-annual stable isotope courses were found to be rather similar for both δ13C and δ18O. Years with particularly low monsoon rain were reflected by increased stable isotope values in the mid-section of intra-annual courses. Distinct patterns with low subseasonal isotope values seem indicative for years with heavy rainfall events from pre-monsoonal cyclones. Rain events from post-monsoonal cyclones may also be recorded; however, only 2 years of observation prevented a more conclusive evaluation.

Abstract Background Regorafenib is one of several FDA‐approved cancer therapies targeting multiple tyrosine kinases. However, there are few subtype‐specific data regarding kinase inhibitor activity in sarcomas. We report results of a single arm, phase II trial of regorafenib in advanced Ewing family sarcomas. Methods Patients with metastatic Ewing family sarcomas (age ≥ 18, ECOG 0–2, good organ function) who had received at least one line of therapy and experienced progression within 6 months of registration were eligible. Prior kinase inhibitors were not allowed. The initial dose of regorafenib was 160 mg oral days 1–21 of a 28‐day cycle. The primary endpoint was estimating progression‐free rate (PFR) at 8 weeks employing RECIST 1.1. Results Thirty patients (median age, 32 years; 33% women [10 patients]; bone primary, 40%; extraskeletal primary, 60%) enrolled at 14 sites. The most common grade 3 or higher toxicities were hypophosphatemia (5 grade 3, 1 grade 4), hypertension (2 grade 3), elevated ALT (2 grade 3). Sixteen patients required dose reductions, most often for hypophosphatemia (n = 7 reductions in 6 patients); two stopped regorafenib for toxicity. There was one death unrelated to treatment in the 30‐day post‐study period. Median progression‐free survival (PFS) was 14.8 weeks (95% CI 7.3–15.9); PFR at 8 weeks by Kaplan–Meier analysis was 63% (95% CI 46–81%). The RECIST 1.1 response rate was 10%. Median OS was 53 weeks (95% CI 37–106 weeks). Conclusions Regorafenib has modest activity in the Ewing family sarcomas. Toxicity was similar to that seen in approval studies.

ABSTRACT Dietary shifts can have a direct impact on the gut microbiome by preferentially selecting for microbes capable of utilizing the various dietary nutrients. The intake of dietary fiber has decreased precipitously in the last century, while consumption of processed foods has increased. Fiber, or microbiota-accessible carbohydrates (MACs), persist in the digestive tract and can be metabolized by specific bacteria encoding fiber-degrading enzymes. The digestion of MACs results in the accumulation of short-chain fatty acids (SCFAs) and other metabolic by-products that are critical to human health. Here, we implemented a 2-week dietary fiber intervention aiming for 40 to 50 g of fiber per day within the context of a course-based undergraduate research experience (CURE) (n = 20). By coupling shotgun metagenomic sequencing and targeted gas chromatography-mass spectrometry (GC-MS), we found that the dietary intervention significantly altered the composition of individual gut microbiomes, accounting for 8.3% of the longitudinal variability within subjects. Notably, microbial taxa that increased in relative abundance as a result of the diet change included known MAC degraders (i.e., Bifidobacterium and Lactobacillus). We further assessed the genetic diversity within Bifidobacterium, assayed by amplification of the groEL gene. Concomitant with microbial composition changes, we show an increase in the abundance of genes involved in inositol degradation. Despite these changes in gut microbiome composition, we did not detect a consistent shift in SCFA abundance. Collectively, our results demonstrate that on a short-term timescale of 2 weeks, increased fiber intake can induce compositional changes of the gut microbiome, including an increase in MAC-degrading bacteria. IMPORTANCE A profound decrease in the consumption of dietary fiber in many parts of the world in the last century may be associated with the increasing prevalence of type II diabetes, colon cancer, and other health problems. A typical U.S. diet includes about ∼15 g of fiber per day, far less fiber than the daily recommended allowance. Changes in dietary fiber intake affect human health not only through the uptake of nutrients directly but also indirectly through changes in the microbial community and their associated metabolism. Here, we conducted a 2-week diet intervention in healthy young adults to investigate the impact of fiber consumption on the gut microbiome. Participants increased their average fiber consumption by 25 g/day on average for 2 weeks. The high-fiber diet intervention altered the gut microbiome of the study participants, including increases in known fiber-degrading microbes, such as Bifidobacterium and Lactobacillus.

Myxopapillary ependymomas are a slow-growing, grade I type glial tumor in the lumbosacral region. More rarely, they can present as extradural, subcutaneous sacrococcygeal, or perisacral masses, and it is under these circumstances that they are more likely to spread. Here, we report the presentation of a sacrococcygeal mass in patient that was initially resected confirming extradural myxopapillary ependymoma. At initial resection, multiple small pulmonary nodules were detected. This mass recurred 2 years later at the resection site with an interval increase in the previously imaged pulmonary nodules. Resection of both the post-sacral mass and largest lung metastasis confirmed recurrent myxopapillary ependymoma with oligometastatic spread. Because these tumors are rare, with extradural presentation being even more infrequent, to this date there are no definitive therapeutic guidelines for initial treatment and continued surveillance. For myxopapillary ependymoma, current standard of care is first-line maximal surgical resection with or without postoperative radiotherapy depending on the extent of disease and extent of resection. However, there remains insufficient evidence on the role of radiotherapy to oligometastatic foci in providing any further survival benefit or extending time to recurrence. Thus, prospective studies assessing the role of upfront treatment of oligometastases with local resection and adjuvant radiotherapy are needed for improved understanding of extradural myxopapillary ependymoma.

Synovial sarcoma (SS) is an aggressive malignancy which accounts for approximately 5–10% of all soft-tissue sarcomas. SS has pathologic and genomic characteristics that define it as a distinct subtype of soft tissue sarcoma (STS). STS subtypes continue to be recognized as distinct entities with specific characteristics, including differential chemo-sensitivity. The objective of this study was to conduct a descriptive review of current data on survival outcomes of systemic anti-cancer therapy specific to SS. A systematic literature review was conducted, using a custom search strategy to search EMBASE, Medline and CENTRAL for clinical trials and observational studies reporting overall survival (OS), progression-free survival (PFS) and/or response for cohorts of at least 50 SS patients. We identified 28 studies meeting these criteria, 25 of which were retrospective studies. Only three prospective studies were identified. Survival reports varied widely between studies based on the population, in particular on the disease stage, and reporting was heterogeneous in terms of the time points reported on. For patients with localized disease, reports of five-year PFS ranged from 26% to 80.7% and five-year OS from 40% to 90.7%, whereas five-year OS for patients with metastatic disease was very low at around 10%; and in one case, 0% was reported. Only four of the included publications reported outcomes by type of systemic anti-cancer therapy received. Our study draws attention to the fact that additional prospective studies to better define the most appropriate treatment for SS in all stages and lines of therapy are still needed.

Within the last two decades, quantum technologies (QT) have made tremendous progress, moving from Nobel Prize award-winning experiments on quantum physics (1997: Chu, Cohen-Tanoudji, Phillips; 2001: Cornell, Ketterle, Wieman; 2005: Hall, Hänsch-, Glauber; 2012: Haroche, Wineland) into a cross-disciplinary field of applied research. Technologies are being developed now that explicitly address individual quantum states and make use of the ‘strange’ quantum properties, such as superposition and entanglement. The field comprises four domains: quantum communication, where individual or entangled photons are used to transmit data in a provably secure way; quantum simulation, where well-controlled quantum systems are used to reproduce the behaviour of other, less accessible quantum systems; quantum computation, which employs quantum effects to dramatically speed up certain calculations, such as number factoring; and quantum sensing and metrology, where the high sensitivity of coherent quantum systems to external perturbations is exploited to enhance the performance of measurements of physical quantities. In Europe, the QT community has profited from several EC funded coordination projects, which, among other things, have coordinated the creation of a 150-page QT Roadmap ( http://qurope.eu/h2020/qtflagship/roadmap2016 ). This article presents an updated summary of this roadmap.

Rhabdomyosarcomatous dedifferentiation of GIST following tyrosine kinase inhibitor (TKI) therapy is rare, with only a handful of cases previously reported in the literature. Herein we present a case of metastatic GIST initially treated with imatinib that developed radiographic evidence of progression after 8 months of standard dose therapy with continued progression despite attempts at using dose-escalated imatinib 400 mg bid. Due to the patient’s worsening clinical symptoms and radiographic concerns for colonic thickening, abscess, and extraluminal air, the patient underwent a palliative resection of a large heterogeneous mass arising from the posterior stomach and several metastatic foci. Pathology revealed a dedifferentiated GIST with rhabdomyosarcomatous features. This report will highlight the unique features of this case and review the existing literature.

No Brasil, nos anos recentes, e acompanhando a maior participação dos municípios nas ações de saúde, observa-se a necessidade crescente de instrumentos que possam contribuir para a melhor formação de gestores locais, complementares às atividades de natureza acadêmica. Nesse sentido realizou-se estudo com o objetivo de construir processo de capacitação de gestores mediante seleção de focos de abordagem para identificar estratégias efetivas para modificação das condições de saúde. Foi feita uma experiência para desenvolvimento de "estudos de casos", com 8 municípios considerados bem sucedidos das regiões Norte e Nordeste do Brasil, com utilização da abordagem por focos na estruturação das informações. Com base nessas informações, foi realizado seminário com 21 gestores locais das duas regiões, reunindo pequenos grupos e intermediando com atividades coletivas. Durante o seminário, gestores municipais de saúde adquiriram maior conhecimento das estratégias implementadas e identificaram alternativas concretas de intervenção para as suas realidades. A proposta metodológica de ensino por estudo de caso utilizando uma prévia elaboração conceitual mediante o agrupamento das diversas dimensões dos casos, facilitou a formação de gestores municipais de saúde a partir de experiências práticas.

Recent advances in sarcoma genomics have identified novel mutations in the PI3K pathway in human sarcomas. Here, we use a mouse model of primary soft-tissue sarcoma for preclinical testing of doxorubicin and inhibitors of the PI3K pathway: BKM120 (PI3K inhibitor) and BEZ235 (a dual PI3K/mTOR inhibitor). Doxorubicin-treated tumors (n=15) showed a partial response rate of 6.6%, just as the majority of human sarcomas do not respond to doxorubicin. Treatment with BKM120 elicited a partial response in 50% of tumors (n=10), which was also seen in combination with doxorubicin (n=10). Additionally, BKM120 treatment produced a robust delay in tumor growth kinetics. BEZ235-treated tumors (n=9) showed a complete response rate of 11.1%. Combining BEZ235 with doxorubicin (n=10) increased the complete response rate to 50% (P=0.035). These studies demonstrate that PI3K pathway inhibition is a viable and attractive target for soft-tissue sarcomas.

BACKGROUND: The invasion of habitats by non-indigenous species (NIS) occurs at a global scale and can generate significant ecological, evolutionary, economic and social consequences. Estuarine and coastal ecosystems are particularly vulnerable to pollution from numerous sources due to years of human-induced degradation and shipping. Pollution is considered as a class of disturbance with anthropogenic roots and recent studies have concluded that high frequencies of disturbance may facilitate invasions by increasing the availability of resources. METHODOLOGY/PRINCIPAL FINDINGS: To examine the effects of heavy metal pollution as disturbance in shaping patterns of exotic versus native diversity in marine fouling communities we exposed fouling communities to different concentrations of copper in one temperate (Virginia) and one tropical (Panama) region. Diversity was categorized as total, native and non-indigenous and we also incorporated taxonomic and functional richness. Our findings indicate that total fouling diversity decreased with increasing copper pollution, whether taxonomic or functional diversity is considered. Both native and non-indigenous richness decreased with increasing copper concentrations at the tropical site whereas at the temperate site, non-indigenous richness was too low to detect any effect. CONCLUSIONS/SIGNIFICANCE: Non-indigenous richness decreased with increasing metal concentrations, contradicting previous investigations that evaluate the influence of heavy metal pollution on diversity and invasibility of fouling assemblages. These results provide first insights on how the invasive species pool in a certain region may play a key role in the disturbance vs. non-indigenous diversity relationship.

Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy.

Undifferentiated pleomorphic sarcoma/Malignant Fibrous Histiocytoma (MFH) is one of the most common subtypes of human soft tissue sarcoma. Using cross species genomic analysis, we define a geneset from the LSL-Kras(G12D); Trp53(Flox/Flox) mouse model of soft tissue sarcoma that is highly enriched in human MFH. With this mouse geneset as a filter, we identify expression of the RAS target FOXM1 in human MFH. Expression of Foxm1 is elevated in mouse sarcomas that metastasize to the lung and tissue microarray analysis of human MFH correlates overexpression of FOXM1 with metastasis. These results suggest that genomic alterations present in human MFH are conserved in the LSL-Kras(G12D); p53(Flox/Flox) mouse model of soft tissue sarcoma and demonstrate the utility of this pre-clinical model.

BACKGROUND: Human activities have increased atmospheric concentrations of carbon dioxide by 36% during the past 200 years. One third of all anthropogenic CO(2) has been absorbed by the oceans, reducing pH by about 0.1 of a unit and significantly altering their carbonate chemistry. There is widespread concern that these changes are altering marine habitats severely, but little or no attention has been given to the biota of estuarine and coastal settings, ecosystems that are less pH buffered because of naturally reduced alkalinity. METHODOLOGY/PRINCIPAL FINDINGS: To address CO(2)-induced changes to estuarine calcification, veliger larvae of two oyster species, the Eastern oyster (Crassostrea virginica), and the Suminoe oyster (Crassostrea ariakensis) were grown in estuarine water under four pCO(2) regimes, 280, 380, 560 and 800 microatm, to simulate atmospheric conditions in the pre-industrial era, present, and projected future concentrations in 50 and 100 years respectively. CO(2) manipulations were made using an automated negative feedback control system that allowed continuous and precise control over the pCO(2) in experimental aquaria. Larval growth was measured using image analysis, and calcification was measured by chemical analysis of calcium in their shells. C. virginica experienced a 16% decrease in shell area and a 42% reduction in calcium content when pre-industrial and end of 21(st) century pCO(2) treatments were compared. C. ariakensis showed no change to either growth or calcification. Both species demonstrated net calcification and growth, even when aragonite was undersaturated, a result that runs counter to previous expectations for invertebrate larvae that produce aragonite shells. CONCLUSIONS AND SIGNIFICANCE: Our results suggest that temperate estuarine and coastal ecosystems are vulnerable to the expected changes in water chemistry due to elevated atmospheric CO(2) and that biological responses to acidification, especially calcifying biota, will be species-specific and therefore much more variable and complex than reported previously.

No Brasil, nos anos recentes, e acompanhando a maior participação dos municípios nas ações de saúde, observa-se a necessidade crescente de instrumentos que possam contribuir para a melhor formação de gestores locais, complementares às atividades de natureza acadêmica. Nesse sentido realizou-se estudo com o objetivo de construir processo de capacitação de gestores mediante seleção de focos de abordagem para identificar estratégias efetivas para modificação das condições de saúde. Foi feita uma experiência para desenvolvimento de "estudos de casos", com 8 municípios considerados bem sucedidos das regiões Norte e Nordeste do Brasil, com utilização da abordagem por focos na estruturação das informações. Com base nessas informações, foi realizado seminário com 21 gestores locais das duas regiões, reunindo pequenos grupos e intermediando com atividades coletivas. Durante o seminário, gestores municipais de saúde adquiriram maior conhecimento das estratégias implementadas e identificaram alternativas concretas de intervenção para as suas realidades. A proposta metodológica de ensino por estudo de caso utilizando uma prévia elaboração conceitual mediante o agrupamento das diversas dimensões dos casos, facilitou a formação de gestores municipais de saúde a partir de experiências práticas.

Atmospheric radio-frequency driven non-equilibrium microplasma jets in an argon/silane/hydrogen gas mixture are characterised and analysed with respect to the reaction pathway, which leads to the formation of silicon nanoparticles. Optical emission spectroscopy is used to obtain initial information about possible plasma chemistry processes and high-time-resolution images uncover the mode of operation of the discharge. It is demonstrated that the effect of the way the electric field is applied (parallel or perpendicular to the gas flow), the gas flow magnitude, and varying the gas mixture can result in three different operation modes—filamentary plasma with a stationary filament, diffuse-like plasma with the filament changing its position, and a diffuse non-filamentary plasma—being formed in the one millimetre inner diameter tube with ring electrodes, which apply an electric field parallel to the gas flow (a parallel-field plasma). An electric field applied perpendicular to the gas flow (a cross-field plasma) results only in a homogeneous diffuse discharge with low plasma density. The nanoparticles synthesised in the microplasma jet are studied by scanning electron microscopy and dynamic light scattering. The experimental results reveal that the silane precursor can very probably be fully dissociated in the parallel-field plasma and particles with sizes almost independent of silane concentration are generated. In contrast, silane is only weakly fragmented in the cross-field plasma and negative ions are formed. Particle size reacts very sensitively to silane concentration in this case and is a result of a condensation of radicals or ions on the particle surface. [ABSTRACT FROM AUTHOR]

Background: Preoperative evaluation of axillary lymph node status is crucial for the selection of both systemic and surgical treatment in early breast cancer. This study assessed the particular role of additional shear wave elastography (SWE) in axillary staging in patients undergoing initial breast cancer diagnostics., Methods: One hundred patients undergoing axillary lymph node biopsy due to a sonographically suspicious axillary lymph node were prospectively evaluated with SWE using virtual touch tissue imaging quantification (VTIQ). Mean values of tissue stiffness for axillary tissue and lymph node tissue were measured prior to core-cut biopsy of the lymph node. All lymph nodes were clip-marked during the biopsy. Cut-off values to differentiate between malignant and benign lymph nodes were defined using Youden's index., Results: Lymph nodes with evidence of malignant tumor cells in the final pathological examination showed a significantly higher velocity as measured by SWE, with a mean velocity of 3.48 ± 1.58 m/s compared to 2.33 ± 0.62 m/s of benign lymph nodes (p < 0.0001). The statistically optimal cutoff to differentiate between malignant and benign lymph nodes was 2.66 m/s with a sensitivity of 69.8% and a specificity of 87.5%., Conclusions: Lymph node metastases assessed with SWE showed significantly higher elasticity values compared to benign lymph nodes. Thus, SWE provides an additional useful and quantifiable parameter for the sonographic assessment of suspicious axillary lymph nodes in the context of pre-therapeutic axillary staging in order to differentiate between benign and metastatic processes and support the guidance of definitive biopsy work-up., Critical Relevance Statement: Shear-wave elastography provides an additional useful and quantifiable parameter for the assessment of suspicious axillary lymph nodes in the context of pre-therapeutic axillary staging in order to differentiate between benign and metastatic processes and support guiding the definitive biopsy work-up., Key Points: SWE is a quantifiable ultrasound parameter in breast cancer diagnosis. SWE shows a significantly higher velocity in malignant lymph nodes. SWE is useful in improving the sensitivity and specificity of axillary staging., (© 2024. The Author(s).)

Whereas rhinoplasty with a reduction of the dorsum and modification of the tip is a common procedure among Caucasians, augmentation of the dorsum remains a challenge in Asians. Choice of the ideal grafting material for dorsal augmentation is a matter of preference and remains under discussion. Autologous and alloplastic materials have their advantages and disadvantages. We report our experiences of the extrusion of alloplastic materials and their management. We report of 18 patients, who had rhinoplasty in the past for dorsal augmentation with alloplastic material. Augmentation rhinoplasty was performed in Asia ( n  = 15) and Germany ( n  = 3). All cases showed recurrent signs of foreign body infection and/or partial extrusion and therefore underwent revision surgery in our centers. Once all patients had been successfully treated with antibiotics, we performed a one-stage revision rhinoplasty with explantation of the alloplastic material and subsequent reconstruction with autologous rib cartilage. The nasal dorsum was augmented with either solid rib cartilage grafts, diced cartilage in fascia, or free diced cartilage in platelet-rich fibrin. All patients received pre-, peri-, and postoperative antibiotics. The outcome was screened via clinical examination, ultrasound examination pre- and postoperatively, two-dimensional/three-dimensional (3D) imaging, and magnetic resonance imaging scans.Alloplastic augmentation of the nasal dorsum runs the risk of foreign body reaction, recurrent infections, uncontrolled scarring, and unsatisfying long-term results. We have obtained a series of aesthetically and functionally satisfying results after single-stage revision surgery with autologous cartilage and demonstrate a variety of novel postoperative screening tools including 3D imaging and high-frequency ultrasound. LEVEL OF EVIDENCE:  N/A., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Contrary to Ni 2+ - and Co 2+ -induced allergic contact dermatitis (ACD), reactions against Pd 2+ are rare. However, Pd 2+ activates a larger T cell fraction in vitro, suggesting an inefficient skin penetration., Objectives: This study compares Ni 2+ , Co 2+ and Pd 2+ skin penetration from commonly used diagnostic patch test preparations (PTPs) and aqueous metal salt solutions., Methods: Using Franz diffusion cell assays, we applied the metals in PTPs (5% NiSO 4 , 1% CoCl 2 , 2% PdCl 2 and 3% Na 2 PdCl 4 ) and in solution to pigskin for 48 h, thereby mirroring the time frame of a patch test. The different compartments were analysed individually by inductively coupled plasma mass spectrometry., Results: Metal ions were mainly retained in the upper stratum corneum layers. After application of PTPs, concentrations in the viable skin were lower for Pd 2+ (1 and 7 μM) compared to Ni 2+ and Co 2+ (54 and 17 μM)., Conclusions: Ni 2+ and Co 2+ penetrated the skin more efficiently than Pd 2+ and thus may sensitize and elicit ACD more easily. This was observed for ions applied in petrolatum and aqueous solutions. We hypothesize that the differently charged metal complexes are responsible for the varying skin penetration behaviours., (© 2024 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Targeted approaches such as targeted axillary dissection (TAD) or sentinel lymph node biopsy (SLNB) showed false-negative rates of < 10% compared with axillary lymph node dissection (ALND) in patients with nodal-positive breast cancer undergoing neoadjuvant systemic treatment (NAST). We aimed to evaluate real-world oncologic outcomes for different axillary staging techniques., Methods: We identified nodal-positive breast cancer patients undergoing NAST from 2016 to 2021 from the state cancer registry of Baden-Wuerttemberg, Germany. Invasive disease-free survival (iDFS) was assessed using Kaplan-Meier statistics and multivariate Cox regression models (adjusted for age, ypN stage, ypT stage, and tumor biologic subtype)., Results: A total of 2698 patients with a median follow-up of 24.7 months were identified: 2204 underwent ALND, 460 underwent SLNB (255 with ≥ 3 sentinel lymph nodes [SLNs] removed, 205 with 1-2 SLNs removed), and 34 underwent TAD. iDFS 3 years after surgery was 69.7% (ALND), 76.6% (SLNB with ≥ 3 SLNs removed), 76.7% (SLNB with < 3 SLNs removed), and 78.7% (TAD). Multivariate Cox regression analysis showed no significant influence of different axillary staging techniques on iDFS (hazard ratio [HR] for SLNB with < 3 SLNs removed 0.96, 95% confidence interval [CI] 0.62-1.50; HR for SLNB with ≥ 3 SLNs removed 0.86, 95% CI 0.56-1.3; HR for TAD 0.23, 95% CI 0.03-1.64; ALND reference), and for ypN+ (HR 1.92, 95% CI 1.49-2.49), triple-negative breast cancer (HR 2.35, 95% CI 1.80-3.06), and ypT3-4 (HR 2.93, 95% CI 2.02-4.24)., Conclusion: These real-world data provide evidence that patient selection for de-escalated axillary surgery for patients with nodal-positive breast cancer undergoing NAST was successfully adopted and no early alarm signals of iDFS detriment were detected., (© 2024. The Author(s).)

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown., Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node., Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis., Exposure: Omission of ALND after SLNB or TAD., Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed., Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55)., Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Objectives: Septorhinoplasty (SRPL) can improve quality of life (QoL) in functional and aesthetical aspects of the nose. A key factor compromising postoperative satisfaction is symptoms of body dysmorphic disorder (BDD), defined by excessive concerns and distress over slight or imagined physical defects. Although a high prevalence of BDD in SRPL patients is evident, the effect of positive screening on BDD and other psychiatric disorders is understudied. It was hypothesized that patients screening positive for BDD, depression or anxiety do not show increased postoperative QoL., Methods: A multicenter, prospective study including 259 patients. For psychiatric evaluation, the BDD concern questionnaire-aesthetic version and the Hospital Anxiety and Depression Scale were used; for disease-specific QoL the Rhinoplasty Outcomes Evaluation (ROE) and the Functional Rhinoplasty Outcome Inventory (FROI-17)., Results: In preoperative evaluation, 32.5% had a positive screening for BDD, 42.2% for increased anxiety, and 32.9% for depression. Mean QoL improved in the whole cohort (FROI total score: 54.4 ± 21.8 to 32.8 ± 23.7 and ROE: 32.3 ± 15.6 to 69.8 ± 23.1, both p < 0.001). Patients screening positive for BDD, depression or anxiety did show an increased postoperative QoL, but to a significantly lower degree and with lower pre- and postoperative QoL levels., Conclusions: SRPL patients show a high prevalence of BDD symptoms, elevated anxiety, and depression. These subgroups show lower QoL levels and an impaired QoL increase after surgery. Rhinoplasty surgeons must be aware of the disorders and their symptoms, discuss potential concerns with the patients, and potentially refer them to a specialist., Level of Evidence: 3 Laryngoscope, 134:2187-2193, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Pre-therapeutic histologic diagnosis through image-guided core needle biopsy (CNB) or vacuum-assisted biopsy (VAB) for suspicious breast findings is a standard procedure. Despite the moderate risk of bleeding, a significant proportion of patients are on temporary or permanent anti-coagulation therapy (ACT) or anti-platelet therapy (APT). Currently, there are no established guidelines for managing biopsies in such patients, leading to varying approaches in clinical practice., Methods: An online survey was conducted among all members of the breast ultrasound working group at the German Society for Ultrasound in Medicine (DEGUM) and the working group for breast diagnostics at the German Radiology Society (DRG). It included n = 51 questions about individual risk perception of biopsy-related bleeding complications and the specific management of biopsies on ACT/APT., Results: A total of 332 experts participated, with 51.8% reporting the absence of a standardized management plan for breast biopsies on ACT/APT. Concerning specific ACT/APT medications, the survey revealed discrepancies in risk perception and management: The majority preferred discontinuing medication with directly acting oral anti-coagulants (DOACs; CNB: 66.9%; VAB: 91.1%), phenprocoumon (CNB: 74.9%; VAB: 96.7%), or therapeutic heparin (CNB: 46.1%; VAB: 72.7%). However, there was a lower inclination to discontinue acetylsalicylic acid (ASA; CNB: 15.2%; VAB: 50.3%) or prophylactic heparin (CNB: 11.9%, VAB: 36.3%)., Conclusion: Breast biopsies for patients on ASA or prophylactic heparin are deemed safe and part of standard clinical practice. However, despite available feasibility studies, conducting breast biopsies on ACT medications such as DOACs or phenprocoumon appears feasible only for a minority of experts., Competing Interests: The authors declare that they have no conflicts of interest. All authors are members of one (or both) of the participating working groups., (© 2024 S. Karger AG, Basel.)

Objectives: Response assessment to neoadjuvant systemic treatment (NAST) to guide individualized treatment in breast cancer is a clinical research priority. We aimed to develop an intelligent algorithm using multi-modal pretreatment ultrasound and tomosynthesis radiomics features in addition to clinical variables to predict pathologic complete response (pCR) prior to the initiation of therapy., Methods: We used retrospective data on patients who underwent ultrasound and tomosynthesis before starting NAST. We developed a support vector machine algorithm using pretreatment ultrasound and tomosynthesis radiomics features in addition to patient and tumor variables to predict pCR status (ypT0 and ypN0). Findings were compared to the histopathologic evaluation of the surgical specimen. The main outcome measures were area under the curve (AUC) and false-negative rate (FNR)., Results: We included 720 patients, 504 in the development set and 216 in the validation set. Median age was 51.6 years and 33.6% (242 of 720) achieved pCR. The addition of radiomics features significantly improved the performance of the algorithm (AUC 0.72 to 0.81; p = 0.007). The FNR of the multi-modal radiomics and clinical algorithm was 6.7% (10 of 150 with missed residual cancer). Surface/volume ratio at tomosynthesis and peritumoral entropy characteristics at ultrasound were the most relevant radiomics. Hormonal receptors and HER-2 status were the most important clinical predictors., Conclusion: A multi-modal machine learning algorithm with pretreatment clinical, ultrasound, and tomosynthesis radiomics features may aid in predicting residual cancer after NAST. Pending prospective validation, this may facilitate individually tailored NAST regimens., Clinical Relevance Statement: Multi-modal radiomics using pretreatment ultrasound and tomosynthesis showed significant improvement in assessing response to NAST compared to an algorithm using clinical variables only. Further prospective validation of our findings seems warranted to enable individualized predictions of NAST outcomes., Key Points: • We proposed a multi-modal machine learning algorithm with pretreatment clinical, ultrasound, and tomosynthesis radiomics features to predict response to neoadjuvant breast cancer treatment. • Compared with the clinical algorithm, the AUC of this integrative algorithm is significantly higher. • Used prior to the initiative of therapy, our algorithm can identify patients who will experience pathologic complete response following neoadjuvant therapy with a high negative predictive value., (© 2023. The Author(s).)

Objectives: Septorhinoplasty (SRPL) and functional endoscopic sinus surgery (FESS) are two frequently performed surgeries to improve quality of life (QoL) in patients with nasal symptoms. It has been demonstrated as a safe combination regarding complication rates, but patient satisfaction in concurrent surgery has not been adequately studied yet., Methods: Patients undergoing sole FESS due to chronic rhinosinusitis (n = 57), sole SRPL (n = 148), and concurrent surgery (n = 62) were prospectively evaluated for their disease-specific QoL before and one year after surgery. Each procedure was performed by the same surgeon (OCB). For SRPL, the patient-reported outcome measures Rhinoplasty Outcomes Evaluation (ROE) and Functional Rhinoplasty Outcome Inventory (FROI-17) were utilized, and for chronic rhinosinusitis, the Sino-Nasal Outcome Test-22 (SNOT22)., Results: All three groups showed significant improvement in the postoperative QoL measurements (all p < 0.01). The postoperative improvements were slightly smaller in the concurrent surgery group compared with the single surgery groups measured with ROE (combined: +55.2 ± 9.3, single: +58.8 ± 9.8, p = 0.02), FROI total score (combined: +47.6 ± 5.2, single: +49 ± 5.4; p = 0.08) and SNOT22 (combined: +33.1 ± 6.7, single +34.5 ± 7, p = 0.26)., Conclusions: SRPL, FESS, and combined surgery improve disease-specific QoL. When applicable, surgeons may offer the benefits of a combined procedure without compromising the QoL gain., Level of Evidence: 3 Laryngoscope, 134:1239-1245, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Patients with triple-negative breast cancer (TNBC) exhibit a fast tumor growth rate and poor survival outcomes. In this study, we aimed to develop and compare intelligent algorithms using ultrasound radiomics features in addition to clinical variables to identify patients with TNBC prior to histopathologic diagnosis., Methods: We used single-center, retrospective data of patients who underwent ultrasound before histopathologic verification and subsequent neoadjuvant systemic treatment (NAST). We developed a logistic regression with an elastic net penalty algorithm using pretreatment ultrasound radiomics features in addition to patient and tumor variables to identify patients with TNBC. Findings were compared to the histopathologic evaluation of the biopsy specimen. The main outcome measure was the area under the curve (AUC)., Results: We included 1161 patients, 813 in the development set and 348 in the validation set. Median age was 50.1 years and 24.4% (283 of 1161) had TNBC. The integrative model using radiomics and clinical information showed significantly better performance in identifying TNBC compared to the radiomics model (AUC: 0.71, 95% confidence interval [CI]: 0.65-0.76 versus 0.64, 95% CI: 0.57-0.71, P = .004). The five most important variables were cN status, shape surface volume ratio (SA:V), gray level co-occurrence matrix (GLCM) correlation, gray level dependence matrix (GLDM) dependence nonuniformity normalized, and age. Patients with TNBC were more often categorized as BI-RADS 4 than BI-RADS 5 compared to non-TNBC patients (P = .002)., Conclusion: A machine learning algorithm showed promising potential to identify patients with TNBC using ultrasound radiomics features and clinical information prior to histopathologic evaluation., (© 2023 The Authors. Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

Background: Obstetrics and gynecology (OB/GYN) is an essential medical field that focuses on women's health. Universities aim to provide high-quality healthcare services to women through comprehensive education of medical students. In Germany, medical education is undergoing a phase of restructuring towards the implementation of competency-based learning. The objective of the current survey was to gain insights into the teaching methods, resources, and challenges at German medical universities in the field OB/GYN. This aims to document the current state of medical education and derive potential suggestions for improvements in the era of competency-based learning. The survey was conducted with teaching coordinators from the majority of OB/GYN departments at German universities., Methods: A questionnaire was sent to the teaching coordinators in all 41 OB/GYN departments at German university hospitals. The survey was delivered via email with a link to an online survey platform., Results: The study received 30 responses from 41 universities. Differences were observed in the work environment of teaching coordinators concerning release from clinical duties for teaching purposes and specialized academic training. Overall, medical education and student motivation were perceived positively, with noticeable gaps, particularly in practical gynecological training. Deficiencies in supervision and feedback mechanisms were also evident. Subfields such as urogynecology and reproductive medicine appear to be underrepresented in the curriculum, correlating with poorer student performance. E-learning was widely utilized and considered advantageous., Conclusion: The present study provides valuable insights into the current state of medical education in OB/GYN at German universities from the perspective of teaching experts. We highlight current deficits, discuss approaches to overcome present obstacles, and provide suggestions for improvement., (© 2024. The Author(s).)

Psychological assessment plays a crucial role in the preoperative phase of septorhinoplasty (SRPL), exerting potential influence on both pre- and postoperative aspects of quality of life (QoL). In this prospective study, SRPL patients were systematically screened using two validated questionnaires for body dysmorphic disorder (BDD) and one each for anxiety, depression, and somatic symptom disorder (SSD). Nasal perception was evaluated utilizing two disease-specific, self-report instruments: The Rhinoplasty Outcomes Evaluation (ROE) and the Functional Rhinoplasty Outcome Inventory-17 (FROI-17). A total of 95 patients were enrolled. Positive screening rates were 40.4 and 28.3% for BDD, 37.3% for elevated anxiety, 16.4% for depression, and 22.4% for SSD. Mean scores on the ROE and FROI indicated lower QoL in all positive screening groups. Statistically significant differences were observed for anxiety (FROI total score: 47.1 ± 14.6 to 37.8 ± 16.2; p  = 0.021) and BDD (ROE: 43.7 ± 15.7 to 32.5 ± 15.5; p  = 0.003 and FROI total score: 47.4 ± 15.3 to 37.8 ± 17.1; p  = 0.014). The Hospital Anxiety and Depression Scale exhibited a significant correlation with the preoperative FROI score ( r  = 0.34, p  = 0.005). Patients with positive screenings for depression, anxiety, BDD, and SSD demonstrated compromised QoL during preoperative assessments compared with their negative counterparts, reflecting diminished nasal perception in both esthetic and functional dimensions. Surgeons must be cognizant of these psychological aspects during preoperative evaluations., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The proliferation marker Ki-67 is a major pathological feature for the description of the state of disease in breast cancer. It helps to define the molecular subtype and to stratify between therapy regimens in early breast cancer and helps to assess the therapy response. Circulating tumor cells (CTCs) are a negative prognostic biomarker for progression free (PFS) and overall survival (OS) in patients with metastatic breast cancer. Therefore, the CTC count is often described as surrogate for the tumor burden. Both, decrease of Ki-67 and CTC count are considered as evidence for therapy response. The presented work analyzed the correlation between the Ki-67 indices of metastatic tissue biopsies and CTC counts in biopsy time-adjacent peripheral blood samples., Patients and Methods: Blood samples from 70 metastatic breast cancer patients were obtained before the start of a new line of systemic therapy. CTCs were enumerated using CellSearch® (Menarini Silicon Biosystems, Bologna, Italy) whereas intact CTCs (iCTCs) and non-intact or apoptotic CTCs (aCTCs) were distinguished using morphologic criteria. The proportion of cells expressing Ki-67 was evaluated using immunohistochemistry on biopsies of metastases obtained concurrently with CTC sampling before the start of a new line of systemic therapy., Results: 65.7% of patients had a Ki-67 index of > 25%. 28.6% of patients had ≥ 5, 47.1% ≥ 1 iCTCs. 37.1% had ≥ 5, 51.4% ≥ 1 aCTCs. No correlation was shown between Ki-67 index and iCTC and aCTC count (r = 0.05 resp. r = 0.05, Spearman's correlation index). High CTC-counts did not coincide with high Ki-67 index. High Ki-67, ≥ 5 iCTCs and aCTCs are associated with poor progression free (PFS) and overall survival (OS)., Conclusion: CTCs and Ki-67 are independent prognostic markers in metastatic breast cancer. High Ki-67 in metastatic tumor tissue is not correlated to high iCTC or aCTC counts in peripheral blood., (© 2023. The Author(s).)

Objectives: Shear wave elastography (SWE) is increasingly used in breast cancer diagnostics. However, large, prospective, multicenter data evaluating the reliability of SWE is missing. We evaluated the intra- and interobserver reliability of SWE in patients with breast lesions categorized as BIRADS 3 or 4., Methods: We used data of 1288 women at 12 institutions in 7 countries with breast lesions categorized as BIRADS 3 to 4 who underwent conventional B-mode ultrasound and SWE. 1243 (96.5%) women had three repetitive conventional B-mode ultrasounds as well as SWE measurements performed by a board-certified senior physician. 375 of 1288 (29.1%) women received an additional ultrasound examination with B-mode and SWE by a second physician. Intraclass correlation coefficients (ICC) were calculated to examine intra- and interobserver reliability., Results: ICC for intraobserver reliability showed an excellent correlation with ICC >0.9, while interobserver reliability was moderate with ICC of 0.7. There were no clinically significant differences in intraobserver reliability when SWE was performed in lesions categorized as BI-RADS 3 or 4 as well as in histopathologically benign or malignant lesions., Conclusion: Reliability of additional SWE was evaluated on a study cohort consisting of 1288 breast lesions categorized as BI-RADS 3 and 4. SWE shows an excellent intraobserver reliability and a moderate interobserver reliability in the evaluation of solid breast masses., (© 2023 The Authors. Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

Background: Chat Generative Pre-Trained Transformer (ChatGPT) is an artificial learning and large language model tool developed by OpenAI in 2022. It utilizes deep learning algorithms to process natural language and generate responses, which renders it suitable for conversational interfaces. ChatGPT's potential to transform medical education and clinical practice is currently being explored, but its capabilities and limitations in this domain remain incompletely investigated. The present study aimed to assess ChatGPT's performance in medical knowledge competency for problem assessment in obstetrics and gynecology (OB/GYN)., Methods: Two datasets were established for analysis: questions (1) from OB/GYN course exams at a German university hospital and (2) from the German medical state licensing exams. In order to assess ChatGPT's performance, questions were entered into the chat interface, and responses were documented. A quantitative analysis compared ChatGPT's accuracy with that of medical students for different levels of difficulty and types of questions. Additionally, a qualitative analysis assessed the quality of ChatGPT's responses regarding ease of understanding, conciseness, accuracy, completeness, and relevance. Non-obvious insights generated by ChatGPT were evaluated, and a density index of insights was established in order to quantify the tool's ability to provide students with relevant and concise medical knowledge., Results: ChatGPT demonstrated consistent and comparable performance across both datasets. It provided correct responses at a rate comparable with that of medical students, thereby indicating its ability to handle a diverse spectrum of questions ranging from general knowledge to complex clinical case presentations. The tool's accuracy was partly affected by question difficulty in the medical state exam dataset. Our qualitative assessment revealed that ChatGPT provided mostly accurate, complete, and relevant answers. ChatGPT additionally provided many non-obvious insights, especially in correctly answered questions, which indicates its potential for enhancing autonomous medical learning., Conclusion: ChatGPT has promise as a supplementary tool in medical education and clinical practice. Its ability to provide accurate and insightful responses showcases its adaptability to complex clinical scenarios. As AI technologies continue to evolve, ChatGPT and similar tools may contribute to more efficient and personalized learning experiences and assistance for health care providers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Riedel, Kaefinger, Stuehrenberg, Ritter, Amann, Graf, Recker, Klein, Kiechle, Riedel and Meyer.)