Important Patient Factors Research Articles

Perioperative fluid management: evidence-based consensus recommendations from the international multidisciplinary PeriOperative Quality Initiative

Fluid therapy is an integral component of perioperative management. In light of emerging evidence in this area, the Perioperative Quality Initiative (POQI) convened an international multiprofessional expert meeting to generate evidence-based consensus recommendations for fluid management in patients undergoing surgery. This article provides a summary of the recommendations for perioperative fluid management of surgical patients from the preoperative period until hospital discharge and for all types of elective and emergency surgery, apart from burn injuries and head and neck surgery. Where evidence was lacking, recommendations for future research were generated. Specific recommendations are made for fluid management in elective major noncardiac surgery, cardiopulmonary bypass, thoracic surgery, neurosurgery, minor noncardiac surgery under general anaesthesia, and critical illness. There are ongoing gaps in knowledge resulting in variation in practice and some disagreement with our consensus recommendations. Perioperative fluid management should be individualised, taking into account the type of surgery and important patient factors, including intravascular volume status and acute and chronic comorbidities. Recommendations are made for further research in perioperative fluid management to address important gaps.

CTIM-07. A PHASE II, OPEN LABEL, SINGLE ARM STUDY OF NIVOLUMAB FOR RECURRENT OR PROGRESSIVE IDH MUTANT GLIOMAS WITH PRIOR EXPOSURE TO ALKYLATING AGENTS

Abstract BACKGROUND Somatic mutations in isocitrate dehydrogenase 1 (IDH1) are an important prognostic factor in patients with gliomas. IDH-mutant gliomas are prone to develop hypermutation after exposure to alkylating agents; in other solid tumors, hypermutation may be a predictive biomarker for PD-1 inhibitor response. In this study, we hypothesize that this specific subgroup of patients would clinically benefit from nivolumab as measured by overall response rate (ORR), duration of response (DOR), median progression-free survival (PFS), and overall survival (OS). METHODS Patients aged 18 years and older with recurrent/progressive IDH-mutant (WHO Grades 2-4) gliomas and prior exposure to alkylating agents were included. Nivolumab was given 240 mg q2w for 8 cycles, then 480 mg q4w until progression, toxicity, study withdrawal, or completion at 2 years. Efficacy was evaluated by ORR of partial (PR) and complete responses (CR) per RANO criteria; low-grade glioma RANO criteria was used for patients with non-enhancing disease. Secondary endpoints included median PFS, median OS, DOR. Toxicity and survival were followed every 3 months until death/study completion. RESULTS Thirty-three patients (66.7% male) were evaluable at study completion. Histology consisted of oligodendroglioma (N=11; 55% Grade 3) and astrocytoma (N=22; 36% Grade 3, 32% Grade 4). Median number of prior lines of systemic therapy was 1 (range 1-6). Median dexamethasone dose at screening was 0 mg (range 0-4). ORR was 9% with two PR and one CR, median DOR 33 months. 11 (32%) patients had stable disease (7 stable for 6+ months) with median PFS 2.2 months and median OS 29.1 months. There were two treatment-related Grade 3 adverse events (lymphopenia and hypotension). One patient discontinued treatment for Grade 2 transaminitis. CONCLUSIONS Though the primary endpoint was not met, three patients have ongoing CR and PR at 54+, 33+ and 24+ months. Future combination therapies with PD-1 inhibitors may increase efficacy in recurrent IDH-mutant gliomas.

The impact of tricuspid regurgitation on the timing of pulmonary valve replacement in adult patients after Tetralogy of Fallot repair

Abstract Background Tricuspid regurgitation (TR) in patients with repaired tetralogy of Fallot (rTOF) is an important finding with a wide spectrum of etiologies. TR represents an important risk factor in adult patients with rTOF, influencing clinical outcomes and the requirement for additional surgical interventions. In this study, we reviewed the long-term outcomes of TR in ACHD patients with rTOF as well as its impact on the timing of surgical pulmonary valve replacement (PVR). Methods This was a retrospective analysis of a single institutional cohort which included 149 ACHD patients with a history of rTOF (transannular patch only) with CMR data, complete follow-up, and a recent (< 1 year) outpatient clinic visit. Results Overall follow-up time was 25.5 years (95% CI 24.5,26.4). Between 2002 and 2021, 93 patients required isolated PVR at a mean time from TOF repair of 16.6 years (95% CI 15.5,17.7) and at a mean age of 17.9 years (95% CI 16.8,19.0). In the whole cohort, significant TR was associated with a two-fold increase in the likelihood of requiring PVR (log-rank p = 0-.0023, HR 2.02; 1.09-4-47). Moderate to severe TR was more frequent in those who underwent VSD closure through a right atriotomy (17 versus 0, p = .0002) and affected time to PVR (13.9 versus 16.3 years, p = .0071), with equal preoperative RVEDVi at CMR. After PVR, RVEDVi normalized in all patients, regardless of the preoperative amount of TR (median 115.3 ml/m2 versus 112.3 ml/m2, p = .7). At a median time of 6.5 years from PVR, 13 patients (13/93, 14%) underwent redo PVR. Conclusions The preoperative severity of tricuspid regurgitation (TR) may have a substantial role on the likelihood of patients needing PVR at a younger age. This, in turn, could result in a reduced duration of freedom from valve failure. Replacing the pulmonary valve too early can effectively increase the lifetime number of procedures, preserving the function of the tricuspid valve at the time of TOF repair is of paramount importance.

A machine learning-based workflow for predicting transplant outcomes in patients with sickle cell disease.

Allogeneic haematopoietic cell transplantation (HCT) with HLA-matched sibling donor remains the most established curative therapeutic option for patients with sickle cell disease (SCD). However, it is not without risks, highlighting the need for a risk stratification system. Utilizing a machine learning (ML) approach that combines clinical and imaging variables, we identified red cell distribution width and renal organ damage as important risk factors for patients undergoing HCT. This ML-based algorithm, similar to an approach previously reported for predicting mortality in patients with SCD, should be applicable to risk factor discovery in similar studies.

The current attitudes and practices of dentists in Australia towards composite repair: A cross-sectional survey study.

Whether to replace or repair a composite restoration is controversial and varies among clinicians. This study was designed to collect information on the attitudes and practices of Australian dentists towards composite repair. An electronic 16-item questionnaire was distributed online on Australian clinicians' dental forum with a URL address and instructions on completing the survey. The questionnaire remained accessible for 2 months. The data collected were analysed statistically using descriptive, average rank, Pearson chi-square and Kruskal-Wallis tests at α = 0.05. Repair of composite restorations was a widely accepted treatment modality among surveyed dentists. Despite this, approximately half of clinicians reported the prognosis of repaired restorations to be worse when compared to replacement. The most cited indications for repair were partial loss or fracture of the restoration, while the most common reason for repair was because this treatment modality was more conservative in terms of tooth structure removal. Most important patient factor influencing decision to repair composite restoration was caries risk of the patient (n = 50). Most significant situational factor to consider in decision whether to repair was previous (failed) attempts to repair (n = 74). The most important tooth level factor was the proximity of restoration to pulp (mean statistic rank 2.22). The most common composite surface treatment employed by participants bonding to old composite was acid etching (n = 87), and the main reason participants employed their chosen surface treatment was based on personal experience (n = 72). The repair of composite restorations was a commonly performed procedure that is well accepted but may still be viewed as an inferior treatment to replacement by many Australian dentists. Most dentists agreed on indications for repair restorations and surface conditioning techniques, but there was wide variation in opinions overall. Due to the lack of high-quality evidence regarding composite repair techniques, dentists tend to rely on personal experience to guide their clinical decisions.

Exploring barriers to completing referral appointments for cancer genetic services in a rural state.

83 Background: Genetic counseling and testing promotes awareness and management of hereditary cancer risk. Barriers exist to accessing cancer genetic services, particularly among those with healthcare disparities, i.e., those facing geographic and socioeconomic barriers. These barriers impact not only the ability to obtain a referral but also whether the initial appointment is scheduled and completed. This study explored referrals and what factors were associated with whether appointments were successfully completed in a predominantly rural state (Maine). Methods: Medical records were reviewed for patients referred to the state’s largest health system-based cancer genetic program from 2017 through 2023. We evaluated factors that may be associated with referral completion within 90 days. These included: year of referral, patient factors, clinical factors, and health system factors. Associations were examined using univariate logistic regression models. Results: A total of 11,643 referrals were placed and examined over the period studied. Despite a steady increase in the number of referrals, the percent of referrals that were successfully completed decreased over time (54.04% in 2017 to 51.06% in 2023). Patients with older age and whose primary language was identified as English had greater likelihood of completing the referral (OR = 1.01; p < 0.001 and OR = 3.37; p < 0.001, respectively). Patients living in isolated rural areas and those without insurance were less likely to complete the referral (OR =0.84 and OR 0.61; p < 0.001, respectively). Patients with a cancer diagnosis were almost three times more likely to complete the referral (OR = 2.93; p < 0.001). Referrals scheduled as telemedicine appointments were less likely to be completed (OR =0.63; p < 0.001); and referrals coming from providers within the health system were twice as likely to be completed (OR = 2.15; p < 0.001). Conclusions: Successful completion of referral appointments to cancer genetic services varied by several important patient, clinical, and health system factors. Further multivariate analyses will be conducted. Strategies including language translation, educational materials, and financial assistance might boost the completion rate for structurally vulnerable patients. Systems aimed at streamlining the scheduling process are needed to support all individuals in accessing cancer genetic services, with a focus on those with healthcare disparities.

Prognostic factors after radical local therapy for oligo-recurrence of non-small cell lung cancer.

Oligo-recurrence refers to the presence of a limited number of metachronous recurrences that can be treated with radical local therapy, and most patients have a good prognosis. However, the clinical course after local therapy for oligo-recurrence of non-small cell lung cancer (NSCLC) varies, and the prognostic factors are unclear. The aim of this study was to elucidate the prognostic factors of patients with oligo-recurrence of NSCLC who underwent radical local therapy. Between 2004 and 2015, 901 patients who underwent complete resection for NSCLC were included. We defined oligo-recurrence as two or fewer recurrences and retrospectively examined the factors that affected post-recurrence survival in patients who underwent radical local therapy for oligo-recurrence. Recurrence was confirmed in 267 patients, and among them, 125 experienced oligo-recurrence. Eighty-five patients with oligo-recurrence received local therapy, and their 5-year post-recurrence survival rate was 42.8%. Multivariable analysis of the prognostic factors of these patients revealed that single recurrence (hazard ratio = 2.19, P = 0.005) and systemic therapy (hazard ratio = 1.75, P = 0.043) were significant favorable prognostic factors associated with post-recurrence survival. However, the presence or absence of epidermal growth factor gene mutations, which is generally a prognostic factor for NSCLC recurrence, did not affect the prognosis of these patients. The number of recurrences and receiving systemic therapy are important prognostic factors for patients with oligo-recurrence who undergo radical local therapy, and these patients have a particularly favorable prognosis.

Clinical outcomes and supragingival microbiota analysis around dental implants and teeth in patients with a history of periodontitis: a preliminary study of 6 months follow-up.

To investigate the supragingival microbiome surrounding dental implants and neighbouring tooth in periodontitis history and periodontally healthy patients. Subjects with a history of periodontitis (test) and periodontally healthy subjects (control) received one of two types of dental implants with different surface characteristics: sandblasted acid-etched (SLA) or precision dimension laser-treated (PDL). Periodontal clinical measurements were collected at baseline (V1), 3 months after implant placement (V4), at zirconia crown placement (V6) and 3 months after zirconia crown placement (V8). Supragingival bacterial microbiota was studied using Illumina MiSeq sequencing. Supragingival microbial community on SLA implants in test group significantly differed to control group at V8 (p < 0.05). A longitudinal shift displaying microbial dysbiosis occurred on SLA implants (p < 0.05) and adjacent teeth (p < 0.05) among test patients from V6 to V8. On PDL implants and the adjacent tooth, no significant difference between test and control groups from V6 to V8 (p > 0.05). Co-occurrence network in test group of SLA implants and the adjacent tooth at V8 showed increased disease-associated bacteria and reduced health-associated bacteria. Health-associated bacteria were dominant in control group of SLA implants at V8. The surface characteristics and prosthetic components of dental implants may be important risk factors in patients with a history of periodontitis. Dysbiosis of supragingival microbiome may predispose dental implants to peri-implant diseases. Thus, a strict supportive periodontal care plan is imperative to prevent early onset of biological complications.

ThP1.6 - Chaperone in Breast Examination: A Comprehensive Systematic Review of Patient and Clinician Perspectives, and Documentation

Abstract Aims The use of chaperones during breast examination is a logical step, particularly in an increasingly litigious society. This review aims to summarise the current information regarding patients’ and clinicians’ perspective in chaperone use in both specialities. Methods A PRISMA compliant search was conducted in electronic databases from inception until April 2023 for qualitative literature regarding patients and clinician perspective in chaperone use in breast and plastic surgery. An inductive thematic analysis in three domains (physician-associated, patient-associated factors and chaperone documentation) was done. Results 10 studies were included after screening 939 articles. Regarding breast surgery, the presence of male and older surgeons, nurse availability, rural setting, and patients’ psychiatric comorbidities were found to increase the propensity of having a chaperone present during consultations. With medico-legal concerns being a prominent factor for male breast surgeons, female breast surgeons highlighted the need for technical support as their main motivation for having a chaperone while logistical issue was a common hindrance. Gender of physicians remained to be an important factor for patients, but conflicting evidence was found regarding patient preferences for chaperone and purpose for having a chaperone present during consultations. Poor documentation was generally observed despite implementing quality improvement projects. Conclusion This study emphasizes the vital role of chaperones in clinical practice, urging a precise definition and targeted resolution for implementation challenges. Patient preferences highlight the need for a personalized approach, and increased awareness among healthcare professionals is essential.

Benefit-Risk Trade-offs and Patient Preferences for Therapy Selection in Ulcerative Colitis: a Multicountry Preference Study.

To help navigate the complex treatment landscape of ulcerative colitis (UC), we quantified the benefit-risk trade-offs that patients were willing to make when choosing treatment. Patients completed an online discrete choice experiment. Eligible patients had a UC diagnosis for ≥6 months, were aged ≥18 years, and resided in France, Germany, Italy, Spain, or the UK. Patients chose between 2 hypothetical treatments set up to ensure trade-offs were made. Clinical trial data, literature review, and patient interviews identified treatment attributes. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. A patient-centric benefit-risk assessment of 200mg of filgotinib was conducted as an example to show how measured trade-offs can be used. Overall, 631 patients participated; patients had a mean age of 42.2 years and were predominantly male (75.3%). Achieving and maintaining clinical remission was the most important factor for patients (RAI 32.4%); to achieve this, patients were willing to accept slightly higher risks of blood clots, serious infections, and malignancies compared with lower risk treatment profiles. Patients also valued the convenience of oral treatments, avoiding steroids, and the ability to attend school/work. The patient-centric benefit-risk assessment suggested patients are significantly more likely to prefer Janus kinase 1 preferential inhibitor filgotinib over placebo. Achieving clinical remission was the highest treatment priority for patients. To attain this, patients were willing to accept some slightly higher risk treatment profiles. Patient choices in the benefit-risk assessment suggested patients were significantly more likely to prefer filgotinib over placebo.

Predicting central lymph node metastasis in papillary thyroid cancer: A nomogram based on clinical, ultrasound and contrast‑enhanced computed tomography characteristics.

Central lymph node (CLN) status is considered to be an important risk factor in patients with papillary thyroid carcinoma (PTC). The aim of the present study was to identify risk factors associated with CLN metastasis (CLNM) for patients with PTC based on preoperative clinical, ultrasound (US) and contrast-enhanced computed tomography (CT) characteristics, and establish a prediction model for treatment plans. A total of 786 patients with a confirmed pathological diagnosis of PTC between January 2021 to December 2022 were included in the present retrospective study, with 550 patients included in the training group and 236 patients enrolled in the validation group (ratio of 7:3). Based on the preoperative clinical, US and contrast-enhanced CT features, univariate and multivariate logistic regression analyses were used to determine the independent predictive factors of CLNM, and a personalized nomogram was constructed. Calibration curve, receiver operating characteristic (ROC) curve and decision curve analyses were used to assess discrimination, calibration and clinical application of the prediction model. As a result, 38.9% (306/786) of patients with PTC and CLNM(-) status before surgery had confirmed CLNM using postoperative pathology. In multivariate analysis, a young age (≤45 years), the male sex, no presence of Hashimoto thyroiditis, isthmic location, microcalcification, inhomogeneous enhancement and capsule invasion were independent predictors of CLNM in patients with PTC. The nomogram integrating these 7 factors exhibited strong discrimination in both the training group [Area under the curve (AUC)=0.826] and the validation group (AUC=0.818). Furthermore, the area under the ROC curve for predicting CLNM based on clinical, US and contrast-enhanced CT features was higher than that without contrast-enhanced CT features (AUC=0.818 and AUC=0.712, respectively). In addition, the calibration curve was appropriately fitted and decision curve analysis confirmed the clinical utility of the nomogram. In conclusion, the present study developed a novel nomogram for preoperative prediction of CLNM, which could provide a basis for prophylactic central lymph node dissection in patients with PTC.

A two-tier feature selection method for predicting mortality risk in ICU patients with acute kidney injury

Acute kidney injury (AKI) is one of the most important lethal factors for patients admitted to intensive care units (ICUs), and timely high-risk prognostic assessment and intervention are essential to improving patient prognosis. In this study, a stacking model using the MIMIC-III dataset with a two-tier feature selection approach was developed to predict the risk of in-hospital mortality in ICU patients admitted for AKI. External validation was performed using separate MIMIC-IV and eICU-CRD. The area under the curve (AUC) was calculated using the stacking model, and features were selected using the Boruta and XGBoost feature selection methods. This study compares the performance of a stacking model using two-tier feature selection with a model using single-tier feature selection (XGBoost: 85; Boruta: 83; two-tier: 0.91). The predictive effectiveness of the stacking model was further validated by using different datasets (Validation 1: 0.83; Validation 2: 0.85) and comparing it with a simpler model and traditional clinical scores (SOFA: 0.65; APACH IV: 0.61). In addition, this study combined interpretable techniques and causal inference to analyze the causal relationship between features and predicted outcomes.

Prognostic significance of negative lymph node count in microsatellite instability-high colorectal cancer

BackgroundMicrosatellite instability-high (MSI-H) tumors, with elevated tumor mutational burden and expression of neoantigens, represent a distinct immune-activated subpopulation in colorectal cancer (CRC), characterized by strong lymph node reaction, locally advanced tumor and higher total lymph nodes harvested (TLN), but less metastatic lymph nodes and fewer incidence of III-IV stage. Host immune response to tumor and lymph nodes may be an important prognostic factor. However, N stage and LNR (Lymph-Node Ratio) have limitations in predicting the prognosis of MSI-H patients. Negative lymph node count (NLC) provided a more precise representation of immune activation status and extent of tumor metastasis. The study aims to detect prognostic significance of NLC in MSI-H CRC patients, and compare it with N stage, TLN and LNR.MethodsRetrospective data of 190 consecutive MSI-H CRC patients who received curative resection were collected. Survival analyses were performed using the Kaplan–Meier method. Clinicopathological variables including NLC, N stage, TLN and LNR were studied in univariate and multivariate COX regression analyses. ROC (receiver operating characteristic curve) and concordance index were employed to compare the differences in predictive efficacy between NLC, N stage, TLN and LNR.ResultsPatients with increased NLC experienced a significantly improved 5-years DFS and OS in Kaplan–Meier analysis, univariate analysis, and multivariate analysis, independent of potential confounders examined. Increased NLC corresponded to elevated 5-years DFS rate and 5-years OS rate. AUC (area under curve) and concordance index of NLC in DFS and OS predicting were both significantly higher than N stage, TLN and LNR.ConclusionsNegative lymph node is an important independent prognostic factor for MSI-H patients. Reduced NLC is associated with tumor recurrence and poor survival, which is a stronger prognostic factor than N stage, TLN and LNR.

Anti-VEGF therapy for the long-term management of diabetic macular edema: a treat-to-target strategy based on macular morphology.

In an aging population, the prevalence and burden of diabetes mellitus, diabetic retinopathy, and vision-threatening diabetic macular edema (DME) are only expected to rise around the world. Similarly to other complications of diabetes mellitus, DME requires long-term management. This article aims to review the current challenges associated with the long-term management of DME, opportunities to improve outcomes for patients, and to develop a treat-to-target strategy based on macular morphology. At present, intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for the management of DME; however, best-achievable vision outcomes with treatment are reliant on frequent injections and close monitoring, which are difficult to maintain in current clinical practice because of the burden this imposes on patients. Achieving and maintaining good vision with treatment are the most important factors for patients with DME. Landmark trials have shown that vision gains with anti-VEGF therapy are typically accompanied by anatomical improvements (e.g., reductions in retinal thickness); therefore, multimodal imaging measures of macular morphology are often used in patients with DME to guide real-world treatment decisions. We would like to propose a hypothetical treat-to-target algorithm to guide physicians on treatment strategies for the long-term management of DME. Alternative measures of retinal fluid (e.g., persistence, stability, location) may be stronger predictors of visual acuity in DME, although further research is required to confirm whether alternate quantifiable biomarkers such as subretinal fluid and intraretinal fluid volumes can be used as a biomarker of clinical improvement. Identifying novel biomarkers and treatments that target neuroinflammation and neurodegeneration, improving patient-physician communication around treatment adherence, and using treat-to-target measures may help to ensure that the long-term benefits of treatment are realized.

CT radiomics combined with clinical and radiological factors predict hematoma expansion in hypertensive intracerebral hemorrhage.

This study aimed to establish a hematoma expansion (HE) prediction model for hypertensive intracerebral hemorrhage (HICH) patients by combining CT radiomics, clinical information, and conventional imaging signs. A retrospective continuous collection of HICH patients from three medical centers was divided into a training set (n = 555), a validation set (n = 239), and a test set (n = 77). Extract radiomics features from baseline CT plain scan images and combine them with clinical information and conventional imaging signs to construct radiomics models, clinical imaging sign models, and hybrid models, respectively. The models will be evaluated using the area under the curve (AUC), clinical decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). In the training, validation, and testing sets, the radiomics model predicts an AUC of HE of 0.885, 0.827, and 0.894, respectively, while the clinical imaging sign model predicts an AUC of HE of 0.759, 0.725, and 0.765, respectively. Glasgow coma scale score at admission, first CT hematoma volume, irregular hematoma shape, and radiomics score were used to construct a hybrid model, with AUCs of 0.901, 0.838, and 0.917, respectively. The DCA shows that the hybrid model had the highest net profit rate. Compared with the radiomics model and the clinical imaging sign model, the hybrid model showed an increase in NRI and IDI. The hybrid model based on CT radiomics combined with clinical and radiological factors can effectively individualize the evaluation of the risk of HE in patients with HICH. CT radiomics combined with clinical information and conventional imaging signs can identify HICH patients with a high risk of HE and provide a basis for clinical-targeted treatment. HE is an important prognostic factor in patients with HICH. The hybrid model predicted HE with training, validation, and test AUCs of 0.901, 0.838, and 0.917, respectively. This model provides a tool for a personalized clinical assessment of early HE risk.

Dysnatremia as a Mortality Marker in Intensive Care Patients with SARS-CoV-2 Infection: A Retrospective Study.

Background and Objectives: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may cause acute respiratory failure, but also remains responsible for many other pathologies, including electrolyte disorders. SARS-CoV-2 infection causes disorders in many systems and can disrupt water homeostasis with thirst and appetite abnormalities. Dysnatremia affects prognosis, and may be associated with mortality in patients admitted to an intensive care unit (ICU) diagnosed with SARS-CoV-2. Materials and Methods: The study included 209 patients admitted to the ICU between 12 April 2021 and 1 March 2022 who were over 18 years old and diagnosed with SARS-CoV-2 infection by clinical and thoracic tomography findings or with a positive reverse transcription polymerase chain reaction (RT-PCR) test result. The laboratory markers, treatment modalities, nutritional, and respiratory support also for outcome evaluation, length of stay in the ICU, total hospitalization duration, and mortality in the ICU were recorded. The laboratory marker comparison was made using admission with the final assessment performed before the time of mortality in the ICU or after discharge. Results: Inotropic requirements among patients were high, which reflected mortality in the ICU. Hypernatremia presence was associated with an increase in enteral support, the inotropic support requirement, and mortality. Hypernatremia was correlated with diabetes mellitus, chronic renal failure, and a longer duration under mechanical ventilation. Conclusions: Hypernatremia was an important risk factor in ICU patients hospitalized for SARS-CoV-2 infection, which was also affected by the treatment regimens given themselves. This complex relationship underlies the importance of proper electrolyte management, especially in patients who were under severe stress and organ failure.

Comparison of Patients' and Surgeons' Expectations before Shoulder Arthroplasty.

Background: Patients suffering from osteoarthritis particularly complain about pain during day and night as well as loss of function. This consequently leads to impaired quality of life and therefore psychological stress. The surgical therapy of choice is joint replacement. Regarding the outcome after operation, expectations might differ between the patient and the surgeon. This can lead to dissatisfaction on both sides. This study aimed to document patients' expectations of a planned shoulder joint replacement. The results were compared with assessments made by shoulder surgeons. Methods: In total, 50 patients scheduled for operative shoulder joint replacement were included in this study, as well as 10 shoulder surgeons. Patients were requested to fill out questionnaires preoperatively to provide sociodemographic data, PROMS (Patient-Reported Outcome Measures) with regard to the pathology and their expectations about surgery in terms of pain relief, gain of range of motion, strength as well as the impact on activities of daily and professional life and sports. In addition, surgeons were asked what they thought their patients expect. Results: The most important goal to achieve for patients was to relieve daytime pain, followed by improvement of self-care and the ability to reach above shoulder level. The most important factors for patients to achieve after operation were 'pain relief' in first place, 'movement' in second and 'strength' in third. This also applied to shoulder surgeons, who ranked 'pain relief' first, followed by 'movement' and 'strength'. When patients where asked what is most important when it comes to choosing their surgeon, 68% voted for 'surgical skills', 28% for 'age/experience', followed by 'empathy', 'sympathy' and 'appearance'. For surgeons, 'age/experience' obtained rank one, 'surgical skills' was ranked second, followed by 'sympathy', 'empathy' and 'appearance'. Surgeons significantly underrated the factor 'empathy' in favor of 'sympathy'. Conclusions: This study shows that patients' expectations for shoulder joint replacement and surgeons' assessments do not differ significantly. Relief from pain and better shoulder movement were crucial for patients to achieve after operation, which was in line with surgeons' expectations. The most important factor for choosing the surgeon was 'surgical skills' for patients, while surgeons thought they would care more about 'age and experience'. This underlines that patients' expectations should be taken into account within the preoperative medical interview. This might allow an optimization of compliance of the patients and lead to a better satisfaction on both sides.

Comprehensive gene expression analysis using RNA sequencing between male and female patients with idiopathic carpal tunnel syndrome.

Idiopathic carpal tunnel syndrome is the most common entrapment neuropathy in hand surgery, and it is characterized by Noninflammatory fibrosis of subsynovial connective tissues. The prevalence and incidence differ between male and female individuals, and the mechanism underlying this difference remains largely unclear. In the present study, we collected subsynovial connective tissues from six male and six female patients diagnosed with idiopathic carpal tunnel syndrome during surgery. We performed a comprehensive gene expression analysis using RNA sequencing to compare the gene expression profiles between male and female patients with idiopathic carpal tunnel syndrome. We identified 26 genes with significantly different expressions between male and female patients, in which POSTN, COL1A1, and COL3A1, which are involved in extracellular matrix organization, and IGF1, an important fibrotic factor, were significantly upregulated in male patients. Immunohistochemistry confirmed the expression of proteins encoded by these genes in tissues, and male patients tended to show increased POSTN expression. Our results indicate that fibrosis of subsynovial connective tissues is induced by different mechanisms in male and female patients, and genes involved in extracellular matrix organization, especially POSTN, might be important factors in male patients. This study provides insight into the pathogenesis of idiopathic carpal syndrome and might contribute to the development of new treatment strategies.

Molecular Subtypes and the Role of TP53 in Diffuse Large B-Cell Lymphoma and Richter Syndrome.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and a heterogeneous entity comprised of several biologically distinct subtypes. Recently, novel genetic classifications of DLBCL have been resolved based on common mutational patterns indicative of distinct pathways of transformation. However, the complicated and costly nature of the novel classifiers has precluded their inclusion into routine practice. In view of this, the status of the TP53 gene, which is mutated or deleted in 20-30% of the cases, has emerged as an important prognostic factor for DLBCL patients, setting itself apart from other predictors. TP53 genetic lesions are particularly enriched in a genetic subtype of DLBCL that shares genomic features with Richter Syndrome, highlighting the possibility of a subset of DLBCL arising from the transformation of an occult chronic lymphocytic leukemia-like malignancy, such as monoclonal B-cell lymphocytosis. Patients with TP53-mutated DLBCL, including those with Richter Syndrome, have a particularly poor prognosis and display inferior responses to standard chemoimmunotherapy regimens. The data presented in this manuscript argue for the need for improved and more practical risk-stratification models for patients with DLBCL and show the potential for the use of TP53 mutational status for prognostication and, in prospect, treatment stratification in DLBCL.

Body composition measures as a determinant of alpelisib-related toxicity.

e13093 Background: Body composition has emerged as an important prognostic factor in patients treated with cancer. Severe depletion of skeletal muscle, sarcopenia, has been associated with poor performance status and worse oncological outcomes. We studied patients with metastatic breast cancer receiving alpelisib, to determine if sarcopenia and additional body composition measures accounting for muscle and adiposity are associated with toxicity. Methods: A retrospective observational analysis was conducted, including 38 women with metastatic breast cancer and a PIK3CA mutation, treated with alpelisib as advanced line of therapy. Sarcopenia was determined by measuring skeletal muscle cross-sectional area at the third lumbar vertebra using computerized tomography. Various body composition metrics were assessed along with drug toxicity, dose reductions, treatment discontinuation, and hospitalizations. Results: Sarcopenia was observed in half of the patients (n=19, 50%), spanning normal weight, overweight, and obese individuals. Among the body composition measures, lower skeletal muscle density (SMD) was associated with an increased risk of treatment-related hyperglycaemia (P=0.03). Additionally, lower visceral adipose tissue (VAT) was associated with alpelisib-induced rash (P=0.04) and hospitalizations (P=0.04). Notably, alpelisib treatment discontinuation was not impacted by alpelisib toxicity. Conclusions: Body composition measures, specifically SMD and VAT may provide an opportunity to identify patients at higher risk for severe alpelisib related hyperglycemia, and cutaneous toxicity. These findings suggest the potential use of body composition assessment to predict toxicity, allowing for personalized therapeutic observation and intervention.