Standard Of Care For Patients Research Articles

Multidisciplinary Applications of AI in Dentistry: Bibliometric Review

This review explores the impact of Artificial Intelligence (AI) in dentistry, reflecting on its potential to reshape traditional practices and meet the increasing demands for high-quality dental care. The aim of this research is to examine how AI has evolved in dentistry over the past two decades, driven by two pivotal questions: “What are the current emerging trends and developments in AI in dentistry?” and “What implications do these trends have for the future of AI in the dental field?”. Utilizing the Scopus database, a bibliometric analysis of the literature from 2000 to 2023 was conducted to address these inquiries. The findings reveal a significant increase in AI-related publications, especially between 2018 and 2023, underscoring a rapid expansion in AI applications that enhance diagnostic precision and treatment planning. Techniques such as Deep Learning (DL) and Neural Networks (NN) have transformed dental practices by enhancing diagnostic precision and reducing workload. AI technologies, particularly Convolutional Neural Networks (CNNs) and Artificial Neural Networks (ANNs), have improved the accuracy of radiographic analysis, from detecting dental pathologies to automating cephalometric evaluations, thereby optimizing treatment outcomes. This advocacy is underpinned by the need for AI applications in dentistry to be both efficacious and ethically sound, ensuring that they not only improve clinical outcomes but also adhere to the highest standards of patient care.

Effectiveness of chest pain center accreditation on the hospital outcome of acute aortic dissection: a nationwide study in China.

The National Chest Pain Center Program (NCPCP) is a nationwide, quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China. The benefits of chest pain center (CPC) accreditation on acute coronary syndrome have been demonstrated. However, there is no evidence to indicate whether CPC accreditation improves outcomes for patients with acute aortic dissection (AAD). We conducted a retrospective observational study of patients with AAD from 1671 hospitals in China, using data from the NCPCP spanning the period from January 1, 2016 to December 31, 2022. The patients were divided into 2 groups: pre-accreditation and post-accreditation admissions. The outcomes examined included in-hospital mortality, misdiagnosis, and Stanford type A AAD surgery. Multivariate logistic regression was employed to explore the relationship between CPC accreditation and in-hospital outcomes. Furthermore, we stratified the hospitals based on their geographical location (Eastern/Central/Western regions) or administrative status (provincial/non-provincial capital areas) to assess the impact of CPC accreditation on AAD patients across various regions. The analysis encompassed a total of 40,848 patients diagnosed with AAD. The post-accreditation group exhibited significantly lower rates of in-hospital mortality and misdiagnosis (12.1% vs. 16.3%, P < 0.001 and 2.9% vs. 5.4%, P < 0.001, respectively) as well as a notably higher rate of Stanford type A AAD surgery (61.1% vs. 42.1%, P < 0.001) compared with the pre-accreditation group. After adjusting for potential covariates, CPC accreditation was associated with substantially reduced risks of in-hospital mortality (adjusted OR 0.644, 95% CI 0.599-0.693) and misdiagnosis (adjusted OR 0.554, 95% CI 0.493-0.624), along with an increase in the proportion of patients undergoing Stanford type A AAD surgery (adjusted OR 1.973, 95% CI 1.797-2.165). Following CPC accreditation, there were significant reductions in in-hospital mortality across various regions, particularly in Western regions (from 21.5 to 14.1%). Moreover, CPC accreditation demonstrated a more pronounced impact on in-hospital mortality in non-provincial cities compared to provincial cities (adjusted OR 0.607 vs. 0.713). CPC accreditation is correlated with improved management and in-hospital outcomes for patients with AAD.

Strategies for adapting under pressure: an interview study in intensive care units

BackgroundHealthcare systems are operating under substantial pressures. Clinicians and managers are constantly having to make adaptations, which are typically improvised, highly variable and not coordinated across teams. This study aimed...

Effects of intermittent calorie restriction in non-diabetic patients with metabolic dysfunction-associated steatotic liver disease

Background & AimsWe compared the effects of a 12-week intermittent calorie restriction (ICR) and standard of care (SOC) diet on liver fat content (LFC) in metabolic dysfunction-associated steatotic liver disease (MASLD) patients. MethodsThis randomized controlled trial included patients with MRI-proton density fat fraction (PDFF) ≥8%. Patients were randomly assigned to the ICR (5:2 diet) or SOC (80% of the recommended calorie intake) groups and stratified according to the body mass index (≥ or <25 kg/m2). The primary outcome was the proportion of patients who achieved a relative LFC reduction as measured by MRI-PDFF ≥30%. ResultsSeventy-two participants underwent randomization (36 patients with and 36 without obesity), and 63 (34 patients with and 29 without obesity) completed the trial. At week 12, a higher proportion of patients in the ICR arm achieved a relative LFC reduction of ≥30% compared to the SOC arm (72.2% vs. 44.4%; P=0.033), which was more prominent in the group with obesity (61.1% vs. 27.7%; P=0.033) than in the group without obesity (83.3% vs. 61.1%; P=0.352). The relative weight reduction was insignificant between the ICR and SOC arms (-5.3% vs. -4.2%; P=0.273); however, it was higher in the ICR arm compared to the SOC arm (-5.5% vs. -2.9%; P=0.039) in the group with obesity. Changes in fibrosis, muscle and fat mass, and liver enzyme levels were similar between the two groups (all P>0.05). ConclusionsThe ICR diet reduced LFC more effectively than SOC in patients with MASLD, particularly in patients with obesity. Additional studies are warranted in larger and more diverse cohorts.

Tumor-Infiltrating Lymphocyte Scoring in Neoadjuvant-Treated Breast Cancer.

Neoadjuvant chemotherapy (NAC) is now the standard of care for patients with locally advanced breast cancer (BC). TIL scoring is prognostic and adds predictive value to the residual cancer burden evaluation after NAC. However, NAC induces changes in the tumor, and the reliability of TIL scoring in post-NAC samples has not yet been studied. H&E- and dual CD3/CD20 chromogenic IHC-stained tissues were scored for stromal and intra-tumoral TIL by two experienced pathologists on pre- and post-treatment BC tissues. Digital TIL scoring was performed using the HALO® image analysis software (version 2.2). In patients with residual disease, we show a good inter-pathologist correlation for stromal TIL on H&E-stained tissues (CCC value 0.73). A good correlation for scoring with both staining methods (CCC 0.81) and the digital TIL scoring (CCC 0.77) was also observed. Overall concordance for TIL scoring in patients with a complete response was however poor. This study reveals there is good reliability for TIL scoring in patients with detectable residual tumors after NAC treatment, which is comparable to the scoring of untreated breast cancer patients. Based on the good consistency observed with digital TIL scoring, the development of a validated algorithm in the future might be advantageous.

Implementation of Regulations and Policies for Nursing Care Quality in Hospitals Worldwide

This systematic review examines the global implementation of regulations and policies aimed at enhancing the quality of nursing care in hospital settings. Through a comprehensive literature search, 20 studies were identified and analyzed. The review focuses on various regulatory frameworks, accreditation standards, and governmental policies that influence nursing care quality. The findings reveal that while regulations generally improve patient outcomes and care standards, challenges such as resource limitations, enforcement variability, and cultural resistance persist. The review concludes with recommendations for future research and policy development to address these challenges and improve nursing care quality globally.

The E3 ubiquitin ligase Herc1 modulates the response to nucleoside analogs in acute myeloid leukemia

AbstractFor several decades, induction therapy with nucleoside analogs, in particular cytarabine (Ara-C) and, to a lesser extent, fludarabine, has been the standard of care for patients diagnosed with acute myeloid leukemia (AML). However, the antitumor efficacy of nucleoside analogs is often limited by intrinsic and acquired drug resistance, thereby leading to poor therapeutic response and suboptimal clinical outcomes. In this study, we used genome-wide CRISPR-based pharmacogenomic screening to map the genetic factors that modulate the response to nucleoside analogs in AML and identified the E3 ubiquitin ligase, Herc1, as a key modulator of Ara-C response in the MLL/AF9 (MA) and the HOXA9/MEIS1 (HM) murine AML models, both in vitro and in vivo. Loss of HERC1 enhanced nucleoside analog–induced cell death in both murine and human AML cell lines by compromising cell cycle progression. In-depth proteomic analysis and subsequent validation identified deoxycytidine kinase as a novel target of Herc1 in MA and HM murine cells. We observed that HERC1 is overexpressed in AML when compared with other cancer types and that higher HERC1 expression was associated with shorter overall survival in patients with AML in the TCGA and BEAT-AML cohorts. Collectively, this study highlights the importance of HERC1 in the response of AML cells to nucleoside analogs, thereby establishing this E3 ubiquitin ligase as a novel predictive biomarker and potential therapeutic target for the treatment of AML.

Gender Disparity of Automatic Implantable Cardioverter-Defibrillator Placement for Primary Prevention: National Inpatient Sample Analysis.

Automatic implantable cardioverter-defibrillators (AICDs) for the primary prevention of sudden cardiac death have become standard care for patients with systolic heart failure (sHF) and ejection fraction ≤35%. While the prevalence of sHF and rates of hospitalization are higher in men, one would expect equivalent rates of implantation in women. We used the Healthcare Cost and Utilization Project's National Inpatient Sample (NIS) from 2009 to 2018 to identify patient visits with sHF and AICD implantation. The comorbidities and outcomes were compared based on gender. There were 15,247,854 inpatient admissions for sHF, of which 60.3% were males (95% CI: 60.1%-60.4%) and 39.8% females (95% CI: 39.7%-39.9%). Approximately 2% of patients (294,726) underwent the insertion of an AICD for primary prevention: 72.3% males (95% CI: 71.9%-72.7%) and 27.72% females (95% CI: 27.3%-28.1%). There was no significant difference in age (p = 0.29), length of stay (p = 0.09), and inpatient mortality (p = 0.18). In this study, women accounted for approximately 40% of patients admitted with the diagnosis of sHF; however, they accounted for less than 30% of patients who underwent the insertion of an AICD. Further research is needed to better understand this gender disparity and identify reasons for the lower rates of AICD placement in women.

62 Prognostic biomarker development using deep learning and spatial proteomics in papillary renal cell carcinoma

Abstract Background Papillary renal cell carcinoma (pRCC) is a prevalent but understudied kidney cancer pathology, constituting 15-20% of cases. While many patients achieve curative therapy using nephrectomy, others go on to develop progressive, metastatic disease with poor overall prognosis. In order to improve the current standards of care for pRCC patients, it is critical to identify new methods to identify high-risk patients likely to require more intense and risk-modulated follow-up. Our goals in this project are two-fold: (1) to identify prognostic patient clusters based on spatial architecture of tumor tissue, and (2) to identify a minimal subset of markers to accurately predict the defined clusters for clinical translation. Methods A tissue microarray of 100 pRCC patients was assayed using multiplex immunofluorescence with a 31-antibody panel with immune- and cancer-related proteins. We have developed novel algorithms to identify spatial neighborhoods and features. These features are then used to identify unsupervised clusters of patients. This new approach to classifying patients allows for a more specific and comprehensive description of each patient tumor’s spatial composition and association with diverse clinical outcomes. Next, we developed attention-based deep learning models capable of predicting these spatially-defined clusters directly from the underlying immunofluorescence images and subsequently profiled these for interpretability by retraining based on individual channels. We assessed each model iteratively on a validation set and a held-out test set for final model selection. We focussed on developing an accurate model with the minimal number of channels to enable development of a cost-efficient biomarker assay for the clinic. Results We performed a systematic analysis of the cellular and spatial phenotypes for each patient in our cohort and identified six (6) major spatial clusters. These clusters are based on the spatial neighborhood composition of the tumors (Fig 1A) and describe the composite effects of cell-cell interactions within a patient tumor. We identified one cluster in particular (cluster #6, mainly associated with spatial interaction of CD163+ macrophages) with a significantly worse prognosis than the other clusters. Using our advanced deep learning models, we have been able to achieve excellent validation accuracy in predicting a variety of clinical phenotypes and spatial features, including patient clusters and histological grade. We wished to then reduce the set of required features and began our efforts in predicting tumor vs. normal based on individual immunofluorescence channels and identified 6 channels with &amp;gt;75% individual predictive accuracy (Fig. 1B). Compositing all 6 markers further improves our accuracy to 90%. This success paves the way for exciting future prospects as we work to extend these efforts to identify a minimal clinically-applicable subset of protein markers. Conclusions The combination of computational spatial proteomics and deep learning models has the potential to identify new biomarkers specific to the spatial organization of patient tumors. We have identified a particular patient cluster with multiple associations with CD163+ macrophages demonstrating poor prognosis; selecting these patients may allow for tailored and more informed patient care. We are also working to enhance our deep learning models to circumvent the need for stepwise spatial analysis and, instead, allow for direct-from-image assessment of patients for particular spatial features indicative of various prognostic indicators. Our identified set of 6 markers serves as a basis for further refinements as we work to identify a minimal set of relevant markers able to predict various clinical outcomes from immunofluorescence imaging, offering a promising new avenue in the field of cancer pathology and biomarker development. DOD CDMRP Funding: yes

Clinical Outcome Comparison between CT-guided versus All MRI-guided Scenarios in Brachytherapy for Cervical Cancer: A Single-Institute Experience

ObjectivesImage-guided adaptive brachytherapy (IGABT) is the standard of care for patients with cervical cancer. The objective of this study was to compare the treatment outcomes and adverse effects of computed tomography (CT)-guided and magnetic resonance imaging (MRI)-guided scenarios. Materials and MethodsData of patients with cervical cancer treated using external beam radiotherapy followed by IGABT from 2012 to 2016 were retrospectively reviewed. CT-guided IGABT was compared with the three modes of MRI-guided IGABT: pre-brachytherapy (MRI Pre-BT) without applicator insertion for fusion, planning MRI with applicator in-place in at least 1 fraction (MRI ≥1Fx), and MRI in every fraction (MRI EveryFx). Patient characteristics, oncologic outcomes, and late radiation toxicity were analyzed using descriptive, survival, and correlation statistics. ResultsOverall, 354 patients were evaluated with a median follow-up of 60 months. The 5-year overall survival (OS) rates were 61.5%, 65.2%, 54.4%, and 63.7% with CT-guided, MRI PreBT, MRI ≥1Fx, and MRI EveryFx IGABT, respectively with no significant differences (p=0.522). The 5-year local control (LC) rates were 92.1%, 87.8%, 80.7%, and 76.5% (p=0.133), respectively, with a significant difference observed between the CT-guided and MRI ≥1Fx (p=0.018). The grade 3–4 late gastrointestinal toxicity rates were 6% in the CT-guided, MRI ≥1Fx, and MRI EveryFx, and 8% in MRI PreBT. The grade 3–4 late genitourinary toxicity rates were 4% in the CT-guided, 2% in MRI PreBT, 1% in MRI ≥1Fx, and none in MRI EveryFx. No significant differences were observed in the oncologic and toxicity outcomes among MRI PreBT, MRI ≥1Fx, and MRI EveryFx. ConclusionCT-guided IGABT yielded an acceptable 5-year OS, LC, and toxicity profile compared with all MRI scenarios and is a potentially feasible option in resource-limited settings.

Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study

The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

Facing the COVID-19 pandemic: An Italian feasibility study of a mixed in-person/telerehabilitation intervention for cancer patients.

The COVID-19 pandemic impacted healthcare organizations, necessitating a rapid transition from in-person to virtual care. Our study explored the feasibility of a mixed in-person/telerehabilitation intervention for cancer patients and its effects on cancer-related fatigue (CRF), quality of life (QoL), physical function, patient satisfaction, and perceived usefulness. TRACE 2020 is an observational prospective study that enrolled adult cancer patients, between January 2021 and March 2023, who were eligible for a rehabilitation program to be provided also in telerehabilitation. Patients were assessed at baseline and after the rehabilitation program. Adherence to sessions, reasons for non-adherence and adverse events were collected. Of the 23 patients enrolled, 87% received a mixed intervention, with an average of 60% in-person sessions and 40% telerehabilitation sessions. Adherence was very high (91%). Evaluation scales showed an improvement in CRF, QoL, and lower limb strength and a relevant increase in patients' level of physical activity (PA). Most patients reported good satisfaction; the few criticisms mainly concerned difficulties in connectivity, lack of physical contact and difficulties in understanding how to perform exercises during telerehabilitation sessions. The physiotherapist underlined the usefulness of the innovative approach and suggested ways to facilitate future implementation. A mixed intervention including telerehabilitation is feasible and accepted by cancer patients. It may have a positive effect on their CRF, QoL, and level of PA and render patient care more flexible. The findings suggest what characteristics the target population for telerehabilitation should have, in order to integrate telerehabilitation in standard care for cancer patients.

Tackling challenges in rare diseases: The ISGACA approach on non-pancreatic cancers in the periampullary region

ObjectiveRare but aggressive cancer types like non-pancreatic periampullary cancers pose unique challenges for cancer research due to their low incidence rates and lack of consensus on optimal treatment strategies, therefore necessitating a collaborative approach. The International Study Group on non-pancreatic peri-Ampullary CAncer (ISGACA) aimed to build a collaborative initiative to pool expertise, funding opportunities, and data from over 60 medical centers, in order to improve outcomes for underrepresented patients with rare cancers. MethodsThe ISGACA approach predefined a stepwise approach including a research scope, establishing a dedicated steering committee, creating a recognizable brand, identifying research gaps, following a well-defined timeline, ensuring robust data collection, addressing legal and ethical considerations, securing financial resources, investing in research ethics training and statistical expertise, raising awareness, creating uniformity, and initiating prospective studies. ResultsOverall, 60 medical centers joined the ISGACA consortium (41 in Europe, 15 in North-America, three in Asia, one in Australia). The database includes 4309 patients. Nine publications and several ongoing studies which in turn allowed for a successful application of research grants. Subsequently, an international consensus meeting established uniform definitions and classifications, and one prospective multicenter international clinical trial has been initiated. ConclusionBy sharing knowledge, expertise, and clinical data, the ISGACA approach has not only gathered sufficient evidence to secure grants and ethical approvals for prospective studies, but also demonstrates options for standardizing patient care and improving outcomes for patients with rare cancers. The ISGACA approach offers a detailed methodology for initiating research on rare cancers and could serve as a replicable model for future research initiatives.

Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

Displaced humeral shaft fractures: Assessment of fracture union and complications following dual plate fixation using an anterior approach

The humeral bone is subject to torsional forces. In case of displaced shaft fractures, internal fixation remains the standard of care. This retrospective two-center study assessed the fracture union rate and complications after dual 3.5 mm locking compression plate (LCP) fixation using an anterolateral approach. Over a 9-year period, 38 patients underwent surgery in two centers. They had a mean age of 53.7 years (15–97, ± standard deviation (SD) 26) and there were three open fracture cases (7.9 %). The dominant side was affected in 21 cases (55.3 %) and there were 11 polytrauma patients (29 %). Mean operative time was 78 min (40–124, ± 19.8 SD). Patients were treated with dual 3.5 mm LCP fixation (6 screws on either side of the fracture line, anterolateral approach without a tourniquet). The first two orthogonal views showing at least 3 cortical bridges out of 4 determined fracture healing, as assessed by two independent raters. Pre- and postoperative complications were tabulated. Clinical outcomes included range of motion (ROM) and return to activities, while functional outcomes were assessed with the Disability of the Arm Shoulder and Hand (DASH), the Constant score, the Subjective Shoulder Score (SSV) and the Mayo Elbow Performance Score (MEPS). Minimum follow-up was 1 year. Four patients were given a shoulder immobilizer to wear for 3 weeks; immediate mobilization was the standard of care for the other patients. Fracture union was achieved in all cases within a mean of 11.7 weeks (6–28 ± 7.1 SD) without any heterotopic ossification of the brachialis muscle. There were eight patients with preoperative radial nerve palsy and two cases of postoperative palsy. There was one surgical site infection (2.6 %). Return to work for active patients was possible in 87 % of cases within a mean of 23 weeks (6–72 ± 11 SD). The Constant score was 84.6 (35–100, ± 13.4 SD), the SSV score was 80.7 (60–100, ± 8.2 SD), the DASH score was 13.5 (0–38.3, ± 8.8 SD) and the MEPS score was 85 (55–100, ± 11.9 SD). Traditional fixation methods provide little control over torsional forces, leading to non-union rates between 3 % and 12 % and delayed union (12 to 20 weeks). The simplicity of the technique described here, and the short operative time, may help explain the low infection rate. Dual plate fixation makes it possible to use more screws and allows nerve exploration and decompression in case of preoperative nerve palsy. Dual plate fixation to treat humeral shaft fractures is a simple and reliable technique.

Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial

Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP. This randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18-75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m2 by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m2 by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov (NCT03278600). Between Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4-51·0) for the site-specific therapy group and 30·9 months (27·6-35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specific therapy than with empirical chemotherapy (9·6 months [95% CI 8·4-11·9] vs 6·6 months [5·5-7·9]; unadjusted hazard ratio 0·68 [95% CI 0·49-0·93]; p=0·017). Among the 167 patients who started planned treatment, 46 (56%) of 82 patients in the site-specific therapy group and 52 (61%) of 85 patients in the empirical chemotherapy group had grade 3 or worse treatment-related adverse events; the most frequent of these in the site-specific therapy and empirical chemotherapy groups were decreased neutrophil count (36 [44%] vs 42 [49%]), decreased white blood cell count (17 [21%] vs 26 [31%]), and anaemia (ten [12%] vs nine [11%]). Treatment-related serious adverse events were reported in five (6%) patients in the site-specific therapy group and two (2%) in the empirical chemotherapy group. No treatment-related deaths were observed. This single-centre randomised trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients. Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT. For the Chinese translation of the abstract see Supplementary Materials section.

Diagnosis and management of isolated serous tubal intraepithelial carcinoma: A qualitative focus group study.

A Serous Tubal Intraepithelial Carcinoma (STIC) without concomitant invasive carcinoma is occasionally identified and associated with a high risk of subsequent peritoneal carcinomatosis. Management needs optimisation. This study explores professionals' opinions and clinical practices regarding the diagnosis, counselling, treatment and follow-up of isolated STIC to facilitate clinical decision making and optimise the direction of future research. A secondary aim is to assess international clinical guidelines. Focus group study. Four online sessions. International panel (n = 12 countries) of gynaecologists, gynaecologic oncologists, pathologists and medical oncologists (n = 49). A semi-structured interview guide was used. Two independent researchers analysed transcripts by open and axial coding. Results were organised in domains. Relevant (inter)national guidelines were screened for recommendations regarding isolated STIC. Professionals' opinions and clinical practices regarding isolated STIC management. Regarding pathology, most professionals identified the SEE-FIM protocol as standard of care for high-risk patients, whereas variation exists in the histopathological examination of fallopian tubes in the general population. Confirmation of STIC diagnosis by a specialised pathologist was recommended. Regarding work-up and follow-up after STIC diagnosis, there was variety and discordance. Data on outcomes is limited. As for treatment, chemotherapy and PARP inhibitors were not recommended by most. Eleven guidelines provided limited recommendations. We identified recommendations and highlighted knowledge gaps in the diagnosis and management of isolated STIC. Moreover, recommendations in clinical guidelines are limited. There is an agreed need for international collaboration for the prospective registration of isolated STIC.

The Prevalence of Sentinel Lymph Node Positivity and Implications for the Utility of Frozen Section Diagnosis Following Neoadjuvant Systemic Therapy in Patients with Clinically Node-Negative HER2-Positive or Triple-Negative Breast Cancer.

Axillary dissection is the standard of care for patients with positive sentinel lymph nodes (SLNs) following neoadjuvant systemic therapy. Frozen section can provide intraoperative information regarding the need for axillary dissection during the index operation. However, there are limited data on the utility of frozen section in patients with clinically node-negative (cN0) HER2-positive or triple-negative breast cancer. We conducted a single-institution observational cohort study including patients with non-inflammatory, cN0, HER2-positive or triple-negative breast cancer treated with neoadjuvant systemic therapy between 2015 and 2019. We estimated the prevalence of SLN positivity and the diagnostic test characteristics of SLN frozen section. Overall, 662 patients were eligible for inclusion, and 44 patients had one or more positive SLNs (prevalence: 6.6%, 95% confidence interval [CI] 4.9-8.8). There were 490 (74.0%) patients who had intraoperative frozen section, and 19 (3.9%) tested positive among 33 (6.7%) with positive final pathology. Frozen section sensitivity was 57.6% (95% CI 39.2-74.5), specificity was 100% (95% CI 99.2-100), positive predictive value was 100% (95% CI 82.4-100), and negative predictive value was 97.0% (95% CI 95.1-98.4). The sensitivity of frozen section for detection of micrometastases or isolated tumor cells was 35.3% (95% CI 14.2-61.7). In patients with cN0 HER2-positive or triple-negative breast cancer who have been treated with neoadjuvant therapy, positive SLNs are uncommon and frozen section sensitivity is modest. Decisions to defer SLN evaluation to final pathology, which may be reasonable in many settings, can be informed, in part, by these findings.

Corneal Collagen Cross-linking for Keratoconus in Pediatric and Developmentally Delayed Patients.

Corneal cross-linking (CXL) is the standard of care in patients with keratoconus but presents unique challenges in children and developmentally delayed patients. We present our clinical decision-making algorithm, CXL surgical technique, and outcomes in these groups. A retrospective chart review was undertaken at a tertiary referral center of all patients who underwent CXL for keratoconus at University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between October 1, 2017, and April 1, 2021. Demographic information along with preoperative, intraoperative, and postoperative ophthalmic examination findings were collected. The main outcome measures were indications of CXL, postoperative complications, and visual acuity (VA). Forty-eight eyes of 34 patients [21 patients (30 eyes) with developmental delay (DD) and 13 patients (18 eyes) with no DD (NDD)] underwent epithelium-off, standard CXL. General anesthesia was used for CXL in all patients except for 3 with NDD. A temporary central tarsorrhaphy was performed in all patients with DD and 7 patients with NDD. The remaining got a bandage contact lens. There were no immediate postoperative complications. A trend toward improvement in VA was noted postoperatively. The mean logMAR VA (with habitual correction) was 0.67 preoperatively and 0.57 postoperatively (P = 0.3) in DD and 0.52 and 0.36, respectively (P = 0.13), in NDD. This retrospective review presents a technique for assessment and treatment of keratoconus in children and those with DD. Our technique ensures timely diagnosis and provides a safe method for CXL in these groups. Temporary central tarsorrhaphy is a well-tolerated option to reduce postoperative pain.

Nursing leadership in disaster preparedness and response lessons learned and future directions

Nursing leadership is integral to effective disaster preparedness and response, demanding agility, strategic planning, and robust resource management. Disasters, both natural and man-made, present unique challenges that require nursing leaders to be adept in rapid decision-making and efficient coordination. The unpredictability of disasters necessitates comprehensive and regularly updated preparedness plans, ensuring nursing teams are well-versed in their roles through continuous training and simulations. Interprofessional collaboration and strong community partnerships are essential, fostering a unified response and efficient resource distribution. Communication remains a cornerstone of disaster management, with clear, timely information dissemination being crucial for coordinating efforts and maintaining public trust. Resource scarcity during disasters, such as shortages of medications and personal protective equipment (PPE), poses significant challenges. Effective resource management strategies are essential to maintain patient care standards and protect healthcare workers. The psychological toll on healthcare providers is another critical issue, with nursing leaders needing to implement support systems that address mental health and promote resilience. Integrating advanced technologies like telehealth and data analytics can enhance disaster response, providing remote care options and enabling predictive modeling for better resource allocation. Innovative approaches in nursing leadership include the use of telehealth for remote consultations and monitoring, data analytics for predictive modeling, and interprofessional education to improve teamwork and coordination. Strengthening community partnerships enhances overall disaster response capacity, ensuring that community-specific needs are addressed. Mental health support for healthcare providers, both immediate and long-term, is vital for maintaining a resilient workforce. Policy advocacy by nursing leaders is crucial to developing robust disaster preparedness frameworks and securing adequate funding. In summary, nursing leadership is pivotal in disaster preparedness and response, with a focus on strategic planning, interprofessional collaboration, effective communication, resource management, mental health support, and the integration of advanced technologies. Emphasizing these areas will enhance the resilience and responsiveness of healthcare systems, ultimately improving outcomes for patients and healthcare providers during disasters.