Individual Patient Research Articles

Individual patient characteristics that heighten risk of Acute Kidney Injury during hot weather: evidence using a novel automated electronic-alerts system.

Individual patient characteristics that heighten risk of Acute Kidney Injury during hot weather: evidence using a novel automated electronic-alerts system.

MRI-Derived Modeling of Disease Progression Patterns in Patients With Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is assumed to follow a steady course that is similar across patients. To date, phenotypic and temporal diversities of TLE evolution remain unknown. In this study, we aimed at simultaneously characterizing these sources of variability based on cross-sectional data. We studied consecutive patients with TLE referred for evaluation by neurologists to the Montreal Neurological Institute epilepsy clinic, who underwent in-patient video EEG monitoring and multimodal imaging at 3 Tesla, comprising 3D T1 and fluid-attenuated inversion recovery and 2D diffusion-weighted MRI. The cohort included patients with drug-resistant epilepsy and patients with drug-responsive epilepsy. The neuropsychological evaluation included Wechsler Adult Intelligence Scale-III and Leonard tapping task. The control group consisted of participants without TLE recruited through advertisement and who underwent the same MRI acquisition as patients. Based on surface-based analysis of key MRI markers of pathology (gray matter morphology and white matter microstructure), the Subtype and Stage Inference algorithm estimated subtypes and stages of brain pathology to which individual patients were assigned. The number of subtypes was determined by running the algorithm 100 times and estimating mean and SD of disease trajectories and the consistency of patients' assignments based on 1,000 bootstrap samples. Effect of normal aging was subtracted from patients. We examined associations with clinical and cognitive parameters and utility for individualized predictions. We studied 82 patients with TLE (52 female, mean age 35 ± 10 years; 11 drug-responsive) and 41 control participants (23 male, mean age 32 ± 8 years). Among 57 operated, 43/37/20 had Engel-I outcome/hippocampal sclerosis/hippocampal isolated gliosis, respectively. We identified 3 trajectory subtypes: S1 (n = 35), led by ipsilateral hippocampal atrophy and gliosis, followed by white-matter damage; S2 (n = 27), characterized by bilateral neocortical atrophy, followed by ipsilateral hippocampal atrophy and gliosis; and S3 (n = 20), typified by bilateral limbic white-matter damage, followed by bilateral hippocampal gliosis. Patients showed high assignability to their subtypes and stages (>90% bootstrap agreement). S1 had the highest proportions of patients with early disease onset (effect size d = 0.27 vs S2, d = 0.73 vs S3), febrile convulsions (χ2 = 3.70), drug resistance (χ2 = 2.94), a positive MRI (χ2 = 8.42), hippocampal sclerosis (χ2 = 7.57), and Engel-I outcome (χ2 = 1.51), pFDR < 0.05 across all comparisons. S2 and S3 exhibited the intermediate and lowest proportions, respectively. Verbal IQ and digit span were lower in S1 (d = 0.65 and d = 0.50, pFDR < 0.05) and S2 (d = 0.76 and d = 1.09, pFDR < 0.05), compared with S3. We observed progressive decline in sequential motor tapping in S1 and S3 (T = -3.38 and T = -4.94, pFDR = 0.027), compared with S2 (T = 2.14, pFDR = 0.035). S3 showed progressive decline in digit span (T = -5.83, p = 0.021). Supervised classifiers trained on subtype and stage outperformed subtype-only and stage-only models predicting drug response in 73% ± 1.0% (vs 70% ± 1.4% and 63% ± 1.3%) and 76% ± 1.6% for Engel-I outcome (vs 71% ± 0.8% and 72% ± 1.1%), pFDR < 0.05 across all comparisons. Cross-sectional MRI-derived models provide reliable prognostic markers of TLE disease evolution, which follows distinct trajectories, each associated with divergent patterns of hippocampal and whole-brain structural alterations, as well as cognitive and clinical profiles.

U.S. Medical Eligibility Criteria for Contraceptive Use, 2024.

The 2024 U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) comprises recommendations for the use of specific contraceptive methods by persons who have certain characteristics or medical conditions. These recommendations for health care providers were updated by CDC after review of the scientific evidence and a meeting with national experts in Atlanta, Georgia, during January 25-27, 2023. The information in this report replaces the 2016 U.S. MEC (CDC. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR 2016:65[No. RR-3]:1-103). Notable updates include 1) the addition of recommendations for persons with chronic kidney disease; 2) revisions to the recommendations for persons with certain characteristics or medical conditions (i.e., breastfeeding, postpartum, postabortion, obesity, surgery, deep venous thrombosis or pulmonary embolism with or without anticoagulant therapy, thrombophilia, superficial venous thrombosis, valvular heart disease, peripartum cardiomyopathy, systemic lupus erythematosus, high risk for HIV infection, cirrhosis, liver tumor, sickle cell disease, solid organ transplantation, and drug interactions with antiretrovirals used for prevention or treatment of HIV infection); and 3) inclusion of new contraceptive methods, including new doses or formulations of combined oral contraceptives, contraceptive patches, vaginal rings, progestin-only pills, levonorgestrel intrauterine devices, and vaginal pH modulator. The recommendations in this report are intended to serve as a source of evidence-based clinical practice guidance for health care providers. The goals of these recommendations are to remove unnecessary medical barriers to accessing and using contraception and to support the provision of person-centered contraceptive counseling and services in a noncoercive manner. Health care providers should always consider the individual clinical circumstances of each person seeking contraceptive services. This report is not intended to be a substitute for professional medical advice for individual patients; when needed, patients should seek advice from their health care providers about contraceptive use.

Optimal Surveillance of Metachronous Gastric Lesion after Endoscopic Resection of Early Gastric Cancer.

Endoscopic resection (ER)-a minimal invasive procedure, compared to surgical gastrectomy, with the advantage of preserving the entire stomach and maintaining the patient's quality of life-is a widely used curative treatment for early gastric cancers (EGCs). Despite its advantages, such as the preservation of the whole stomach, a large area of the gastric mucosa with histologic changes such as atrophy and intestinal metaplasia remains after ER, and so does the risk of metachronous gastric cancers (MGCs). Therefore, regular surveillance endoscopy after curative ER of EGCs is important so that MGCs are detected early and so minimally invasive ER remains a treatment option. To date, the optimal interval for surveillance endoscopy after curative ER of EGCs has not been established. Therefore, this review summarizes the results of the published studies on this topic with the aim of establishing the optimal surveillance interval for early identification of MGCs. Based on my review, the median timing of MGC occurrence is within 3 years, and reports suggest biannual endoscopy during the first 3 years; however, the evidence suggests that individual patient characteristics may influence the risk of MGCs. Therefore, stratified endoscopic strategies for surveillance based on patient characteristics, such as age, family history of gastric cancer, synchronous gastric lesions, and corpus intestinal metaplasia, should be applied.

U.S. Selected Practice Recommendations for Contraceptive Use, 2024.

The 2024 U.S. Selected Practice Recommendations for Contraceptive Use (U.S. SPR) addresses a selected group of common, yet sometimes complex, issues regarding initiation and use of specific contraceptive methods. These recommendations for health care providers were updated by CDC after review of the scientific evidence and a meeting with national experts in Atlanta, Georgia, during January 25-27, 2023. The information in this report replaces the 2016 U.S. SPR (CDC. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR 2016;65[No. RR-4]:1-66). Notable updates include 1) updated recommendations for provision of medications for intrauterine device placement, 2) updated recommendations for bleeding irregularities during implant use, 3) new recommendations for testosterone use and risk for pregnancy, and 4) new recommendations for self-administration of injectable contraception. The recommendations in this report are intended to serve as a source of evidence-based clinical practice guidance for health care providers. The goals of these recommendations are to remove unnecessary medical barriers to accessing and using contraception and to support the provision of person-centered contraceptive counseling and services in a noncoercive manner. Health care providers should always consider the individual clinical circumstances of each person seeking contraceptive services. This report is not intended to be a substitute for professional medical advice for individual patients; when needed, patients should seek advice from their health care providers about contraceptive use.

Endovascular approaches for the treatment of dural carotid-cavernous fistulas: A systematic review.

Dural carotid-cavernous fistulas (dCCFs), also known as indirect carotid-cavernous fistulas, represent abnormal connections between the arterial and venous systems within the cavernous sinus that are typically treated via endovascular approach. We aim to investigate the clinical characteristics of patients with dCCFs based on the endovascular treatment approach and assess angiographic and clinical outcomes. A systematic review of the literature was performed. Data including number of patients, demographics, presenting clinical symptoms, etiology of fistula, Barrow classification, and embolization material were collected and evaluated. Outcome measures collected included degree of fistula occlusion, postoperative symptoms, complications, and mean follow-up time. A total of 52 studies were included examining four primary endovascular approaches for treating dCCFs: transarterial, transfemoral-transvenous (transpetrosal or other), transorbital (percutaneous or via cutdown), and direct transfacial access. Overall data was collected from 736 patients with 817 dCCFs. Transarterial approaches exhibit lower dCCF occlusion rates (75.6%) compared to transvenous techniques via the inferior petrosal sinus (88.1%). The transorbital approach via direct puncture or surgical cutdown offers a more direct path to the cavernous sinus, although with greater complications including risk of orbital hematoma. The direct transfacial vein approach, though limited, shows up to 100% occlusion rates and minimal complications. We provide a comprehensive review of four main endovascular approaches for dCCFs. In summary, available endovascular treatment options for dCCFs have expanded and provide effective solutions with generally favorable outcomes. While the choice of approach depends on individual patient factors and technique availability, traditional transvenous procedures have emerged as the first-line endovascular treatment. There is growing, favorable literature on direct transorbital and transfacial approaches; however, more studies directly comparing these general transvenous options are necessary to refine treatment strategies.

Identifying and reducing risks of neurological complications associated with vaccination.

Vaccines protect against many infectious diseases, including some that can directly or indirectly cause nervous system damage. Serious neurological consequences of immunization are typically extremely rare, although they have the potential to jeopardize vaccination programmes, as demonstrated most recently during the COVID-19 pandemic. Neurologists have an important role in identifying safety signals at population and individual patient levels, as well as providing advice on the benefit-risk profile of vaccination in cohorts of patients with diverse neurological conditions. This article reviews the links between vaccination and neurological disease and considers how emerging signals can be evaluated and their mechanistic basis identified. We review examples of neurotropic infections with live attenuated vaccines, as well as neuroimmunological and neurovascular sequelae of other types of vaccines. We emphasize that such risks are typically dwarfed by neurological complications associated with natural infection and discuss how the risks can be further mitigated. The COVID-19 pandemic has highlighted the need to rapidly identify and minimize neurological risks of vaccination, and we review the structures that need to be developed to protect public health against these risks in the future.

Effect of time of day on outcomes in elective surgery: asystematic review.

The timing of elective surgery could affect clinical outcome because of diurnal rhythms of patient physiology as well as surgical team performance. Waiting times for elective surgery are increasing in many countries, leading to increasing interest in undertaking elective surgery in the evening or at night. We aimed to systematically review the literature on the effect of the timing of elective (but not urgent or emergency) surgery on mortality, morbidity and other clinical outcomes. We searched databases for relevant studies combining the terms 'circadian rhythm' and 'anaesthesia/surgery'. Additional relevant articles were found by hand-searching the references. All studies were screened for bias. Included studies examined daytime vs. evening/night-time surgery, morning vs. afternoon surgery, multiple timeslots or used time as a continuous variable. Nineteen retrospective cohort studies, one prospective cohort study and one randomised controlled trial were included (n = 798,914). Evening/night-time elective surgery was associated with a higher risk of mortality when compared with daytime procedures in three studies (n = 611,230), with odds ratios (95%CI) for mortality ranging from 1.35 (1.16-1.56) to 3.98 (1.54-10.30), while no differences were found in three other studies (n = 142,355). No differences were found for morning vs. afternoon surgery (four studies, n = 3277). However, most studies had a low quality of evidence due to their retrospective nature and because not all studies corrected for patient characteristics. Moreover, the studies were heterogeneous in terms of the reported time slots and clinical outcomes. We found that evening/night-time elective surgery is associated with a higher risk of mortality compared with daytime surgery. However, the quality of evidence was graded as low, and thus, future prospective research should publish individual patient data and standardise outcome measures to allow firm conclusions and facilitate interventions.

Cost Analysis of Routine Histopathologic Evaluation of Specimens Following Total Ankle Arthroplasty.

Routine histopathologic examination of orthopaedic surgical specimens is a standard practice at many institutions. Previous studies have demonstrated that this practice seldom altered patient management for several orthopaedic procedures. As a result, the value of such practices has come into question. The purpose of this study is to determine the cost-effectiveness of routine histopathologic analysis of specimens obtained during total ankle arthroplasty (TAA). A retrospective analysis was performed of patients who underwent uncomplicated primary TAA at a large, academic, health system between January 2015 and December 2021. The postoperative histopathologic diagnoses were compared with the respective patient's preoperative clinical and intraoperative diagnoses. The prevalence of concordant, discrepant, and discordant diagnoses was determined. Cost-effectiveness analysis was conducted to assess the financial implications of obtaining routine specimens for histopathologic examination for TAA. A total of 85 TAAs were identified in 85 individual patients and were included in the present study. A total of 172 specimens were sent for routine histopathologic review. On histopathologic analysis, a final diagnosis was confirmed in 82 (96.5%) of the total specimens reviewed. A discrepant diagnosis was discovered in 3 (3.5%; 2 cases of gout/pseudogout and 1 case of osteonecrosis) cases and 0 (0%) discordant diagnoses were discovered, corresponding to positive and negative predictive values of 97% and 100%, respectively The total estimate of costs incurred for the routine analysis of all specimens included in the study was between $12 299.20 and 17 846.00. The estimated cost to establish each discrepant diagnosis ranged between $4099.73 and $5948.67, and the cost for a discordant diagnosis was unable to be established. Routine histopathologic analysis of specimens obtained during TAA rarely revealed a discordant diagnosis and resulted in no alterations to patients' plan of care. Furthermore, the additional costs of routine histopathologic examination are significant. As such, it is recommended that such interventions in TAA should be performed on a per-case basis at the operating surgeon's discretion.

Corticosteroids for Immune-Related Adverse Events and Checkpoint Inhibitor Efficacy: Analysis of Six Clinical Trials.

Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials. A post hoc analysis was performed on individual patient data from the anti-programmed cell death-1 (anti-PD-1) + anti-cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex. Of the 1,959 patients who received anti-PD-1 + anti-CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HRadj), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HRadj, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HRadj, 1.21 (95% CI, 1.06 to 1.39) and HRadj, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HRadj of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS. Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.

A functional intervention within a cognitive approach to chronic cervical radiculopathy

BackgroundMost patients with cervical radiculopathy improve within the first months without treatment or with non-surgical treatment. A systematic review concluded that these patients improve, regardless of their intervention. Still, many patients are offered surgery, despite limited evidence regarding the indications for surgical treatments. The aim of this article is to describe the intervention that is going to be followed in the non-surgical treatment arm of a randomised controlled trial (RCT) comparing the effectiveness of surgical and non-surgical treatment for patients with cervical radiculopathy.MethodsThe non-surgical intervention is a functional intervention within a cognitive approach founded on previous experiences, and current recommendations for best practice care of musculoskeletal pain and cervical radiculopathy. It is based on the biopsychosocial rather than a biomedical perspective, comprises an interdisciplinary approach (physicians, physiotherapy specialists), and includes brief intervention and graded activities. The intervention consists of 6 sessions over 12 weeks. The primary goals are first, to validate the patients´ symptoms and build a therapeutic alliance, second, to explore the understanding and promote alternatives, and third, to explore problems and opportunities based on patients´ symptoms and function. Motivational factors toward self-management are challenging. We will attempt shared decision-making in planning progress for the individual patient and emphasise learning of practical self-help strategies and encouragement to stay active (reinforcing the positive natural course). General physical activities such as walking will be promoted along with simple functional exercises for the neck- and shoulder region. We will also explore social activity, comorbidities, pain location, sleep, and work-related factors. The health providers will set individualised goals together with each patient.DiscussionThe aim of the intervention is to describe a functional intervention within a cognitive approach for patients with chronic cervical radiculopathy. The effectiveness of the present program will be compared to surgery in a randomised controlled trial.

Prediction of nodal disease in oral squamous cell carcinoma of the tongue: histopathological risk assessment with the focus on depth of invasion.

Cervical lymph node metastasis (CLNM) is one of the most relevant influencing factors for the oncological outcome of patients with oral squamous cell carcinoma (OSCC). Several studies showed that the tumors depth of invasion (DOI) influences the risk for CLNM, however varying across the oral subsites. The aim of this study is to investigate the role of DOI and other risk factors in OSCC of the tongue in relation to the occurrence of occult CLNM. In this retrospective study, n = 139 patients with primary OSCC of the tongue, treated by complete surgical resection (R0) with curative intention between 2013 and 2021, were included. For data analysis, epidemiologic data as well as preoperative tumor staging, surgical therapy including neck management, histopathological tumor data and follow-up were considered. Uni- and multivariate logistic regression were used to determine association between histopathological risk factors and the occurrence of occult CLNM. The rate of occult cervical metastasis was 19.4%. T-staging, cervical nodal disease (pN+) and lymphatic invasion were significantly associated with reduced OS and RFS. While DOI had no relevant influence on the OS and RFS (p = 0.88 and p = 0.91 respectively), there was significant correlation between DOI and the occurrence of occult CLNM (OR: 1.17, 95%CI: 1.05-1.30; p < 0.01). The optimal cutoff in predicting occult CLNM was 6mm (Sensitivity: 84.2%, Specificity: 73.5%, AUC: 0.75). The DOI is a helpful risk parameter to predict the occurrence of occult nodal disease in OSCC of the tongue. Given the critical decision cutoff between 2 and 4mm DOI for performing elective neck dissection in the current guidelines, our data suggests that in these cases, surgical de-escalation could be feasible with close follow-up. This study highlights the relevance of DOI as a risk parameter in the prediction of CLNM with the aim to specify the individual patient risk and to deescalate surgical therapy in order to decrease comorbidities while improving the oncological prognosis.

3D live imaging and phenotyping of CAR-T cell mediated-cytotoxicity using high-throughput Bessel oblique plane microscopy

Clarification of the cytotoxic function of T cells is crucial for understanding human immune responses and immunotherapy procedures. Here, we report a high-throughput Bessel oblique plane microscopy (HBOPM) platform capable of 3D live imaging and phenotyping of chimeric antigen receptor (CAR)-modified T-cell cytotoxicity against cancer cells. The HBOPM platform has the following characteristics: an isotropic subcellular resolution of 320 nm, large-scale scouting over 400 interacting cell pairs, long-term observation across 5 hours, and quantitative analysis of the Terabyte-scale 3D, multichannel, time-lapse image datasets. Using this advanced microscopy platform, several key subcellular events in CAR-T cells are captured and comprehensively analyzed; these events include the instantaneous formation of immune synapses and the sustained changes in the microtubing morphology. Furthermore, we identify the actin retrograde flow speed, the actin depletion coefficient, the microtubule polarization and the contact area of the CAR-T/target cell conjugates as essential parameters strongly correlated with CAR-T-cell cytotoxic function. Our approach will be useful for establishing criteria for quantifying T-cell function in individual patients for all T-cell-based immunotherapies.

Potential, Pitfalls, and Future Directions for Remote Monitoring of Chronic Respiratory Diseases: Multicenter Mixed Methods Study in Routine Cystic Fibrosis Care.

The current literature inadequately addresses the extent to which remote monitoring should be integrated into care models for chronic respiratory diseases (CRDs). This study examined a remote monitoring program (RMP) in cystic fibrosis (CF) by exploring experiences, future perspectives, and use behavior over 3 years, with the aim of developing future directions for remote monitoring in CRDs. This was a mixed methods, multicenter, observational study in 5 Dutch CF centers following a sequential explanatory design. Self-designed questionnaires using the technology acceptance model were sent out to people with CF who had a minimum of 12 months of experience with the RMP and local health care professionals (HCPs). Questionnaire outcomes were used to inform semistructured interviews with HCPs and people with CF. Qualitative findings were reported following the COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist. Anonymous data on use frequency of all people with CF were analyzed. Between the second quarter of 2020 and the end of 2022, a total of 608 people with CF were enrolled in the program, and a total of 9418 lung function tests and 2631 symptom surveys were conducted. In total, 65% (24/37) of HCPs and 89% (72/81) of people with CF responded to the questionnaire, and 7 HCPs and 12 people with CF participated in semistructured interviews. Both people with CF and HCPs were positive about remote monitoring in CF care and found the RMP a good addition to daily care (people with CF: 44/72, 61%; HCPs: 21/24, 88%). Benefits ranged from supporting individual patients to reducing health care consumption. The most valued monitoring tool was home spirometry by both people with CF (66/72, 92%) and HCPs (22/24, 92%). Downsides included the potential to lose sight of patients and negative psychosocial effects, as 17% (12/72) of people with CF experienced some form of stress due to the RMP. A large majority of people with CF (59/72, 82%) and HCPs (22/24, 92%) wanted to keep using the RMP in future, with 79% (19/24) of HCPs and 75% (54/72) of people with CF looking forward to more replacement of in-person care with digital care during periods of well-being. Future perspectives for the RMP were centered on creating hybrid care models, personalizing remote care, and balancing individual benefits with monitoring burden. Remote monitoring has considerable potential in supporting people with CF and HCPs within the CF care model. We identified 4 practice-based future directions for remote monitoring in CF and CRD care. The strategies, ranging from patient driven to prediction driven, can help clinicians, researchers, and policy makers navigate the rapidly changing digital health field, integrate remote monitoring into local care models, and align remote care with patient and clinician needs.

Opioids and personalized analgesia in the perioperative setting: A protocol for five systematic reviews.

Treatment with opioids is a mainstay in perioperative pain management. While the leading treatment paradigm has been procedure-specific pain management, efforts regarding personalized pain treatment are increasing. The OPI•AID project aims to develop personalized algorithms for perioperative pain management, taking demographic, surgical, and anaesthesiologic factors into account. We will undertake five parallel reviews to illuminate current evidence on different aspects of individual responses to perioperative opioid treatment. Inclusion of adult populations in English-written studies. Review-specific searches are developed for the following databases: CENTRAL, MEDLINE, Embase, clinicaltrials.gov, and clinicaltrial.eu. Two authors will independently screen citations, extract data, and assess the risks of bias in each review (QUIPS, PROBAST and RoB2, as relevant). These reviews will evaluate various aspects of perioperative opioid treatment, including individualized treatment strategies, selection of specific opioids, and individual patient responses. These will guide future development of a personalized perioperative opioid treatment algorithm (OPI•AID) that will be validated and tested clinically against standard of care.

Endonasal endoscopic or endoscopic-assisted transcranial surgery of Rathke’s cleft cysts: does the approach and surgical technique influence the radicality and recurrence rate?

Objective: Resections of symptomatic Rathke’s cleft cysts (RCCs) are mainly performed via an endonasal transsphenoidal approach. However, there is a lack of equivalent data in current literature concerning transcranial keyhole approach in the treatment of RCCs. In order to find general recommendations for the surgical treatment of RCCs also with regard to recurrence, the object of this study is the analysis and comparison of both techniques. Methods: Twenty-nine patients having been surgically treated between January 2004 and August 2019 were retrospectively analysed. The transsphenoidal approach was chosen in 16 cases and the transcranial keyhole approach in 13 cases. Both surgical techniques were analyzed and compared concerning preoperative symptoms and cyst characteristics, complications, surgical radicality, endocrinological and ophthalmological outcome and recurrences in patients´ follow up. Results: The postoperative outcome of both techniques was identic and showed highly satisfying success rates with 92% for neurological deficits, 82% for endocrinological dysfunctions and 86% for visual deficits. In contrast, momentous postoperative complications were significantly more likely after transsphenoidal operations. After a mean follow-up time of 5.7 years, the recurrence rates of both cohorts were the same with 0% each. Conclusions: Regarding its equal outcome with its lower complication rate, the authors suggest using the supraorbital keyhole approach for RCCs whose anatomical configuration allow both techniques. Yet, the decision should always consider the surgeon’s personal experience and other individual patient characteristics. Further studies with higher numbers of cases and longer follow-up periods are necessary to analyse the effect of the selected approach on recurrence.

Therapeutic applications of synthetic gene/genetic circuits: a patent review

A significant limitation of numerous current genetic engineering therapy approaches is their limited control over the strength, timing, or cellular context of their therapeutic effect. Synthetic gene/genetic circuits are synthetic biology approaches that can control the generation, transformation, or depletion of a specific DNA, RNA, or protein and provide precise control over gene expression and cellular behavior. They can be designed to perform logical operations by carefully selecting promoters, repressors, and other genetic components. Patent search was performed in Espacenet, resulting in 38 selected patents with 15 most frequent international classifications. Patent embodiments were categorized into applications for the delivery of therapeutic molecules, treatment of infectious diseases, treatment of cancer, treatment of bleeding, and treatment of metabolic disorders. The logic gates of selected genetic circuits are described to comprehensively demonstrate their therapeutic applications. Synthetic gene circuits can be customized for precise control of therapeutic interventions, leading to personalized therapies that respond specifically to individual patient needs, enhancing treatment efficacy and minimizing side effects. They can be highly sensitive biosensors that provide real-time therapy by accurate monitoring various biomarkers or pathogens and appropriately synthesizing a therapeutic molecule. Synthetic gene circuits may also lead to the development of advanced regenerative therapies and to implantable biodevices that produce on-demand bioactive molecules. However, this technology faces challenges for commercial profitability. The genetic circuit designs need adjustments for specific applications, and may have disadvantages like toxicity from multiple regulators, homologous recombination, context dependency, resource overuse, and environmental variability.

Optimizing Glioblastoma, IDH-wildtype Treatment Outcomes : A Radiomics and Support Vector Machine -Based Approach to Overall Survival Estimation.

Glioblastoma multiforme (GBM), particularly the IDH-wildtype type, represents a significant clinical challenge due to its aggressive nature and poor prognosis. Despite advancements in medical imaging and its modalities, survival rates have not improved significantly, demanding innovative treatment planning and outcome prediction approaches. This study utilizes a Support Vector Machine (SVM) classifier using radiomics features to predict the overall survival (OS) of GBM, IDH-wildtype patients to short (< 12 Months) and long (>=12 Months) survivors. A dataset comprising multi-parametric MRI (mpMRI) scans from 574 patients was analyzed. Radiomic features were extracted from T1, T2, FLAIR, and T1-Gd sequences. Low variance features were removed, and Recursive Feature Elimination (RFE) was used to select the most informative features. The SVM model was trained using a k-fold cross-validation approach. Furthermore, clinical parameters such as age, gender, and MGMT promoter methylation status were integrated to enhance prediction accuracy. The model showed reasonable results in terms of cross-validated AUC of 0.84 (95% CI: 0.80-0.90) with (p-value < 0.001) effectively categorizing patients into short and long survivors. Log-rank test (Chi-square statistics) analysis for the developed model was 0.00029 along with the 1.20 Cohen's d effect size. Most importantly, clinical data integration further refined the survival estimates, providing a more fitted prediction that considers individual patient characteristics by Kaplan-Meier curve with p-value<0.0001. The proposed method significantly enhances the predictive accuracy of OS outcomes in GBM, IDH-wildtype patients. By integrating detailed imaging features with key clinical indicators, this model offers a robust tool for personalized treatment planning, potentially improving OS.

Social Determinants of Hepatitis C Virus Infection in the United States, 2016-2021.

This cross-sectional study assessed hepatitis C virus (HCV) antibody and RNA test results performed from 2016 to 2021 at a large US clinical reference laboratory. When individual patient factors (ie, income, education, and race/ethnicity) were not available, estimates from the US Census were linked to the residential zip code. The final analytic cohort comprised 19,543,908 individuals with 23,233,827 HCV antibody and RNA test results. An analysis of progressively increasing poverty quintiles demonstrated an increasing trend in both HCV antibody positivity (from 2.6% in the lowest quintile to 6.9% in the highest, P < 0.001 for trend) and HCV RNA positivity (from 1.0% to 3.6%, P < 0.001 for trend). Increasing levels of education were associated with a decreasing trend in both HCV antibody positivity (from 8.4% in the least educated quintile to 3.0% in the most, P < 0.001 for trend) and HCV RNA positivity (from 4.7% to 1.2%, P < 0.001 for trend). Persistent differences in positivity rates by these social determinants were observed over time. HCV antibody and RNA positivity rates were nearly identical in predominantly Black non-Hispanic, Hispanic, and White non-Hispanic zip codes. However, after adjustment for all other factors in the study, residents of predominantly Black non-Hispanic and Hispanic zip codes were significantly less likely to test positive for HCV RNA (adjusted odds ratios [AOR]: 0.51, 95% confidence interval [CI]: 0.51-0.52; AOR: 0.46, 95% CI: 0.46-0.46, respectively). These findings may benefit targeted intervention initiatives by public health agencies.

Beyond Step Count: Are We Ready to Use Digital Phenotyping to Make Actionable Individual Predictions in Psychiatry?

Some models for mental disorders or behaviors (eg, suicide) have been successfully developed, allowing predictions at the population level. However, current demographic and clinical variables are neither sensitive nor specific enough for making individual actionable clinical predictions. A major hope of the "Decade of the Brain" was that biological measures (biomarkers) would solve these issues and lead to precision psychiatry. However, as models are based on sociodemographic and clinical data, even when these biomarkers differ significantly between groups of patients and control participants, they are still neither sensitive nor specific enough to be applied to individual patients. Technological advances over the past decade offer a promising approach based on new measures that may be essential for understanding mental disorders and predicting their trajectories. Several new tools allow us to continuously monitor objective behavioral measures (eg, hours of sleep) and densely sample subjective measures (eg, mood). The promise of this approach, referred to as digital phenotyping, was recognized almost a decade ago, with its potential impact on psychiatry being compared to the impact of the microscope on biological sciences. However, despite the intuitive belief that collecting densely sampled data (big data) improves clinical outcomes, recent clinical trials have not shown that incorporating digital phenotyping improves clinical outcomes. This viewpoint provides a stepwise development and implementation approach, similar to the one that has been successful in the prediction and prevention of cardiovascular disease, to achieve clinically actionable predictions in psychiatry.