Individual Patient Research Articles

Management of paediatric monomorphic post-transplant lymphoproliferative disorders with low-intensity treatment: A multicentre international experience.

Monomorphic post-transplant lymphoproliferative disorder (mPTLD) is a major cause of morbidity/mortality following solid organ transplant (SOT), with infection, mPTLD progression and organ rejection presenting equal risks. Balancing these risks is challenging, and the intensity of therapy required by individual patients is not defined. Although an increasing body of evidence supports the use of a stepwise escalation of therapy through reduction in immunosuppression (RIS) to rituximab monotherapy and low-dose chemo-immunotherapy, many centres still use B-cell non-Hodgkin lymphoma (B-NHL) protocols, especially when managing Burkitt/Burkitt-like (BL) PTLD. This study sought to define outcomes for children managed in the UK or Spanish centres using low-intensity first-line treatments. Retrospective data were anonymously collected on patients younger than 18years of age, with post-SOT mPTLD diagnosed between 2000 and 2020. Only patients given low-intensity treatment at initial diagnosis were included. Fifty-six patients were identified. Age range was 0.9-18years (median 10.7). Most (62.5%) had early-onset PTLD. Haematopathological analysis showed 75% were diffuse large B-cell like, 14.3% were BL and nine of 33 (27%) harboured a MYC-rearrangement. Stage III-IV disease was present in 78.6%. All but one had RIS, 26 received rituximab monotherapy and 24 low-dose chemo-immunotherapy, mostly R-COP. Intensified B-NHL chemotherapy was required in 10/56 (17.9%). There were a total of 13 deaths in this cohort, three related to PTLD progression. The 1-year overall survival (OS), event-free survival (EFS) and progression-free survival (PFS) were 92.8%, 78.6% and 80.2%, respectively. R-COP provides an effective low-dose chemotherapy option. Escalation to more intensive therapies in the minority of inadequately controlled patients is an effective strategy.

Liquid profiling for patients with advanced cancer is ready for clinical integration

SummaryMolecular profiling of circulating tumor DNA (ctDNA) to guide treatment decisions has found its way into routine management of patients with advanced cancer. This represents a pivotal advancement in precision oncology, offering a non-invasive and fast-tracked method to detecting clinically relevant biomarkers. With the backing of international oncology guidelines, ctDNA analysis is now a standard approach to consider in molecular diagnostics. Despite the promise of ctDNA in refining treatment strategies through the detection of genomic alterations and treatment-relevant biomarkers with high concordance to tissue biopsies, challenges persist. These include the interpretation of discordances due to tumor heterogeneity, sampling biases, and technical limitations, alongside the differentiation of tumor-derived mutations from clonal hematopoiesis. The current consensus supports the utility of comprehensive genomic profiling (CGP) panels for a broad spectrum of actionable targets, while acknowledging the limitations and advocating for a balanced application of “tissue-first” and “plasma-first” approaches tailored to individual patient scenarios. The essential role of molecular tumor boards (MTBs) is in navigating the complexities of ctDNA data interpretation, thereby ensuring the effective incorporation of liquid biopsy into personalized cancer treatment regimens.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. PROSPERO (ID: CRD42023476470).

An Image-Based Interactive Training Method of an Upper Limb Rehabilitation Robot

Aimed at the problem of human–machine interaction between patients and robots in the process of using rehabilitation robots for rehabilitation training, this paper proposes a human–machine interactive control method based on an independently developed upper limb rehabilitation robot. In this method, the camera is used as a sensor, the human skeleton model is used to analyse the moving image, and the key points of the human body are extracted. Then, the three-dimensional coordinates of the key points of the human arm are extracted by depth estimation and spatial geometry, and then the real-time motion data are obtained, and the control instructions of the robot are generated from it to realise the real-time interactive control of the robot. This method can not only improve the adaptability of the system to individual patient differences, but also improve the robustness of the system, which is less affected by environmental changes. The experimental results show that this method can realise real-time control of the rehabilitation robot, and that the robot assists the patient to complete the action with high accuracy. The results show that this control method is effective and can be applied to the fields of robot control and robot-assisted rehabilitation training.

Exploring the Efficacy of Selected Allografts in Chronic Wound Healing: Evidence from Murine Models and Clinical Data for a Proposed Treatment Algorithm.

Chronic wounds can lead to poor outcomes for patients, with risks including amputation and death. In the United States, chronic wounds affect 2.5% of the population and cost up to $28 billion per year in primary healthcare costs. Allograft tissues (dermal, amnion, and amnion/chorion) have shown efficacy in improving healing of chronic, recalcitrant wounds in human patients, as evidenced by multiple clinical trials. Their mechanisms of actions have been relatively understudied, until recently. Research in murine models has shown dermal allografts promote re-epithelialization, amnion allografts promote granulation tissue formation and angiogenesis, and amnion/chorion allografts support all stages of wound healing. These findings not only confirm effectiveness, but they shed light on mechanisms of action responsible for their therapeutic utility in patients. Despite the promise of allografts in chronic wound care, a gap exists in understanding which allografts are most effective during each wound healing stage. The variable efficacy among each type of allograft suggests a mechanistic approach towards a proposed clinical treatment algorithm, based on wound characteristics and patient's needs, may be beneficial. Recent advances in allografts provide a framework for further investigations on how allograft selection can be based on specific needs of individual patients. This requires additional research to identify which allografts support the best outcomes during each stage of the wound healing process as well as utility in specific wound types. Longitudinal human studies investigating the long-term impacts of allografts, particularly in the remodeling phase, are also essential to developing a deeper understanding of their role in sustained wound repair and recovery.

Preoperative Risk Assessment of Early Kidney Graft Loss.

A large proportion of potential organ donors are not utilized for kidney transplantation out of risk of early allograft loss because of donor-related characteristics. These can be summarized using kidney donor profile index (KDPI). Because KDPI affects the choice of the recipient, the predictive ability of KDPI is tied to recipient attributes. These have been questioned to explain most of the predictive ability of KDPI. This study aims to quantify the effect of the donor on early graft loss (EGL) by accounting for nonrandom allocation. This study included patients undergoing kidney transplantation from deceased donors between 2014 and 2020 from the Scientific Registry of Transplantation Recipients. EGL, defined as a return to dialysis or retransplantation during the first posttransplant year, was the primary endpoint. Nonrandom allocation and donor-recipient matching by KDPI necessitated the use of inverse probability treatment weighting, which served to assess the effect of KDPI and mitigate selection bias in a weighted Cox regression model. The study comprised 89 290 transplantations in 88 720 individual patients. Inverse probability treatment weighting resulted in a good balance of recipient covariates across values of continuous KDPI. Weighted analysis showed KDPI to be a significant predictor for short-term outcomes. A comparable (in terms of age, time on dialysis, previous transplants, gender, diabetes status, computed panel-reactive antibodies, and HLA mismatches) average recipient, receiving a kidney from a donor with KDPI 40-60 had a 3.5% risk of EGL increased to a risk of 7.5% if received a kidney from a KDPI >95 donor (hazard ratio, 2.3; 95% confidence interval, 1.9-2.7). However, for all-cause survival KDPI was less influential. The predictive ability of KDPI does not stem from recipient confounding alone. In this large sample-sized study, modeling methods accounting for nonindependence of recipient selection verify graft quality to effectively predict short-term transplantation outcomes.

Management of the Devastated Bladder Outlet after Prostate CANCER Treatment.

Devastating complications of the bladder outlet resulting from prostate cancer treatments are relatively uncommon. However, the combination of the high incidence of prostate cancer and patient longevity after treatment have raised awareness of adverse outcomes deteriorating patients' quality of life. This narrative review discusses the diagnostic work-up and management options for bladder outlet obstruction resulting from prostate cancer treatments, including those that require urinary diversion. The devastated bladder outlet can be a consequence of the treatment of benign conditions, but more frequently from complications of pelvic cancer treatments. Regardless of etiology, the initial treatment ladder involves endoluminal options such as dilation and direct vision internal urethrotomy, with or without intralesional injection of anti-fibrotic agents. If these conservative strategies fail, surgical reconstruction should be considered. Although surgical reconstruction provides the best prospect of durable success, reconstructive procedures are also associated with serious complications. In the worst circumstances, such as prior radiotherapy, failed reconstruction, devastated bladder outlet with end-stage bladders, or patient's severe comorbidities, reconstruction may neither be realistic nor justified. Urinary diversion with or without cystectomy may be the best option for these patients. Thorough patient counseling before treatment selection is of utmost importance. Outcomes and repercussions on quality of life vary extensively with management options. Meticulous preoperative diagnostic evaluation is paramount in selecting the right treatment strategy for each individual patient. The risk of bladder outlet obstruction, and its severest form, devastated bladder outlet, after treatment of prostate cancer is not negligible, especially following radiation. Management includes endoluminal treatment, open or robot-assisted laparoscopic reconstruction, and urinary diversion in the worst circumstances, with varying success rates.

INDIPENDENT PROGNOSTIC VALUE OF SOLUBLE–SUPRESSION OF TUMORIGENICITY (S–ST2) IN PATIENTS AFFECTED BY PULMONARY HYPERTENSION

Abstract Introduction According to ESC 2022 guidelines, pulmonary hypertension (PH) is a hemodynamic condition characterized by mean pulmonary arterial pressure&amp;gt;20 mmHg. Pulmonary arterial hypertension (PAH) represents 5% of the PH, with an unfavorable prognosis primarily because of late diagnosis and treatment. In PAH, it is important to evaluate the individual patient mortality risk through a multiparametric approach: a three–layer model at diagnosis and a four–layer model based on WHO–FC, 6MWD and NT–proBNP at follow up, which allows better discrimination within the intermediate risk group helping therapeutic decision making. The only biomarker included in risk stratification is NT–proBNP; however, in previous studies soluble–Supression of Tumorigenicity 2(s–ST2), a marker of myocardial stress, resulted a strong predictor of death in heart failure and acute coronary syndromes. Aim The aim of this study is to analyze the prognostic value of s–ST2 in patients with pulmonary hypertension. Methods This is a prospective study conducted on 45 PH patients (75% PAH), which were followed for survival. They underwent echocardiography, venous sampling to measure s–ST2 levels, right heart catheterization. All the patients were followed for survival. Results During an average 18–month follow–up, 17 patients died, 76% of whom had pulmonary arterial hypertension (PAH). They showed significantly higher values of s–ST2. sST2&amp;gt;78 ng/ml represents a numerical value with the highest association with mortality in our study population: at 6–12 months the patients with sST2&amp;gt;78 ng/ml showed statistically significant early higher mortality in comparison with sST2 &amp;lt;78 ng/ml patients (Fig. 1). At multivariate analysis s–ST2&amp;gt;78 ng/ml is confirmed to be a statistically significant predictor of mortality, regardless of WHO functional class III–IV, PAPs and NT–proBNP. Furthermore, s–ST2 appears a better early mortality predictor than NT–proBNP, at the limit of statistical significance (Fig. 2). Conclusions In a population of patients with pulmonary hypertension (predominantly PAH) we define a numerical value of sST2&amp;gt;78 ng/ml, which is a prognostic discriminator, independent and incremental to NT–proBNP at short–term follow–up. It allows the clinician the appropriate planning of therapeutic strategies in a condition in which the earliness of therapy affects prognosis.

Dermatopathological diagnosis of porphyria cutanea tarda - Two case reports

Porphyria cutanea tarda and its relationship with HIV and Hepatitis C are highlighted in the case reports. Porphyria cutanea tarda arises from a deficiency in the uroporphyrinogen decarboxylase enzyme, where there is an anomaly in the buildup of specific porphyrins, notably in blood vessels, liver, and skin. It can be either hereditary or acquired. In this context, we have discussed two individual patients with HIV and Hepatitis C who were diagnosed with porphyria cutanea tarda through skin biopsy.

How safe is gene therapy? : Second death after Duchenne therapy

Duchenne muscular dystrophy (DMD) is asevere monogenic hereditary disease with early manifestation and aprogressive course. Treatment options have so far been limited. Gene therapy opens up new options for DMD patients. Against the background of afurther death following DMD gene therapy, the side effects and risks of the gene therapeutics already approved or undergoing clinical trials will be evaluated and alternative gene therapeutics will be described. Based thereon, the future of DMD gene therapy will be discussed. For the first time, in June 2023, delandistrogene moxeparvovec (SRP-9001), agene replacement therapy based on an adeno-associated virus (AAV) vector, was approved in the USA for children aged 4-5years with DMD. Other promising gene therapies are in preclinical development or clinical trials, including CRISPR/Cas9-mediated strategies to restore dystrophin expression. Two deaths following DMD gene therapy with high-dose AAV vectors were attributed to AAV-mediated immune responses. The pre-existing disease underlying the therapy is most likely involved in the fatal AAV toxicity. Although gene therapy applications of AAV vectors are generally considered safe, the systemic administration of high vector doses can lead to severe side effects with apotentially fatal outcome in individual patients, especially after activation of the immune system. In the future, new methods for immunosuppression, reduction of AAV dose and alternative vectors will therefore increasingly come to the fore.

Characterization of Circulating HCV Genotypes: A Cohort Study in Uttar Pradesh, India

Hepatitis C virus infection is one of the main causes of liver disease that can lead to liver cirrhosis and finally to the chronic development of Hepatocellular Carcinoma (HCC). With 8 different HCV genotypes circulating, it becomes necessary to characterize the pathogenesis caused by each one of the HCV genotypes infecting population of a particular setting. Present study aims to identify the circulating Hepatitis C virus (HCV) genotypes in the different areas of State of Uttar Pradesh, India and understand their clinical etiology and related co-morbidities. The patients reporting to Sharda Hospital, Uttar Pradesh, India who were diagnosed positive for HCV were included in the study. The informed consent was obtained and then blood was drawn. In-house primers, for all the 8 genotypes were prepared and RT-PCR was performed. The amplified product was subjected to Agarose gel electrophoresis to identify the genotypes present in individual samples. Total 30 serum samples were taken. Of these, 21 (70%) showed presence of multiple genotypes, while 7 (23.33%) showed positivity for single genotype and two did not show any bands. Presence of multiple genotypes in individual patient has been reported for the first time. The pathological consequences of multiple genotypes within one host need to be studied further in terms of increased risk of developing a chronic liver disease. Further studies are being undertaken to study association of specific HCV genotype and multiple genotypes, Core, NS3 and NS5 viral proteins with the disease progression to develop predictors of liver cirrhosis and HCC.

Classifying Individuals With Rheumatic Conditions as Financially Insecure Using Electronic Health Record Data and Natural Language Processing: Algorithm Derivation and Validation.

We aimed to examine the feasibility of applying natural language processing (NLP) to unstructured electronic health record (EHR) documents to detect the presence of financial insecurity among patients with rheumatologic disease enrolled in an integrated care management program (iCMP). We incorporated supervised, rule-based NLP and statistical methods to identify financial insecurity among patients with rheumatic conditions enrolled in an iCMP (n = 20,395) in a multihospital EHR system. We constructed a lexicon for financial insecurity using data from available knowledge sources and then reviewed EHR notes from 538 randomly selected individuals (training cohort n = 366, validation cohort n = 172). We manually categorized records as having "definite," "possible," or "no" mention of financial insecurity. All available notes were processed using Narrative Information Linear Extraction, a rule-based version of NLP. Models were trained using the NLP features for financial insecurity using logistic, least absolute shrinkage operator (LASSO), and random forest performance characteristic and were compared with the reference standard. A total of 245,142 notes were processed from 538 individual patient records. Financial insecurity was present among 100 (27%) individuals in the training cohort and 63 (37%) in the validation cohort. The LASSO and random forest models performed identically and slightly better than logistic regression, with positive predictive values of 0.90, sensitivities of 0.29, and specificities of 0.98. The development of a context-driven lexicon used with rule-based NLP to extract data that identify financial insecurity is feasible for use and improved the capture for presence of financial insecurity with high accuracy. In the absence of a standard lexicon and construct definition for financial insecurity status, additional studies are needed to optimize the sensitivity of algorithms to categorize financial insecurity with construct validity.

Biomimetic Approach of Brain Vasculature Rapidly Characterizes Inter- and Intra-Patient Migratory Diversity of Glioblastoma.

Glioblastomas exhibit remarkable heterogeneity at various levels, including motility modes and mechanoproperties that contribute to tumor resistance and recurrence. In a recent study using gridded micropatterns mimicking the brain vasculature, glioblastoma cell motility modes, mechanical properties, formin content, and substrate chemistry are linked. Now is presented, SP2G (SPheroid SPreading on Grids), an analytic platform designed to identify the migratory modes of patient-derived glioblastoma cells and rapidly pinpoint the most invasive sub-populations. Tumorspheres are imaged as they spread on gridded micropatterns and analyzed by this semi-automated, open-source, Fiji macro suite that characterizes migration modes accurately. SP2G can reveal intra-patient motility heterogeneity with molecular correlations to specific integrins and EMT markers. This system presents a versatile and potentially pan-cancer workflow to detect diverse invasive tumor sub-populations in patient-derived specimens and offers a valuable tool for therapeutic evaluations at the individual patient level.

Artificial intelligence based data curation: enabling a patient-centric European health data space

The emerging European Health Data Space (EHDS) Regulation opens new prospects for large-scale sharing and re-use of health data. Yet, the proposed regulation suffers from two important limitations: it is designed to benefit the whole population with limited consideration for individuals, and the generation of secondary datasets from heterogeneous, unlinked patient data will remain burdensome. AIDAVA, a Horizon Europe project that started in September 2022, proposes to address both shortcomings by providing patients with an AI-based virtual assistant that maximises automation in the integration and transformation of their health data into an interoperable, longitudinal health record. This personal record can then be used to inform patient-related decisions at the point of care, whether this is the usual point of care or a possible cross-border point of care. The personal record can also be used to generate population datasets for research and policymaking. The proposed solution will enable a much-needed paradigm shift in health data management, implementing a ‘curate once at patient level, use many times’ approach, primarily for the benefit of patients and their care providers, but also for more efficient generation of high-quality secondary datasets. After 15 months, the project shows promising preliminary results in achieving automation in the integration and transformation of heterogeneous data of each individual patient, once the content of the data sources managed by the data holders has been formally described. Additionally, the conceptualization phase of the project identified a set of recommendations for the development of a patient-centric EHDS, significantly facilitating the generation of data for secondary use.

The courage to advocate: How two professions approach public advocacy work.

While health advocacy is an established physician role, most of the educational attention to advocacy has been at the individual patient level. Public advocacy-efforts to effect change at the level of communities, populations or society-remains a poorly defined concept whose educational foundation is underdeveloped. To enrich our understanding of public advocacy, we explored how professionals in two disciplines-medicine and law-have approached its tasks and experienced its challenges. Using constructivist grounded theory, we interviewed 18 professionals (nine physicians, eight lawyers and one qualified in both disciplines) who engage in public advocacy. We used constant comparison throughout an iterative process of data collection and analysis to develop an understanding of what it means to be a professional in the public domain. Public advocacy work occurs at the intersection of personal and professional identities. Lawyers perceived public advocacy as an embedded element of their professional identity, while physicians more often viewed it as outside their core professional scope. Nonetheless, professional identity influenced how both groups conducted their work. Physicians were more likely to draw on professional attitudes (e.g. their orientation towards evidence and their trusted social position), while lawyers were more likely to draw on professional skills (e.g. building an argument and litigating test cases). The work requires courage and often demands that individuals tolerate personal and professional risk. While medicine has enshrined advocacy in its competency frameworks, it is the legal profession whose practitioners more fully embrace advocacy as intrinsic to professional identity, suggesting that roles are difficult to engineer or impose. Collaboration across public-facing professions like medicine and law creates opportunities to reimagine public advocacy, to identify the skills required to do it well and to refresh educational strategies.

Relationship of oral bacterial number with medical hospitalization costs in analysis of Diagnosis Procedure Combination database from single institution in Japan

Oral bacteria are known to be associated with perioperative complications during hospitalization. However, no presented reports have clarified the relationship of oral bacterial number with medical costs for inpatients. The Diagnosis Procedure Combination (DPC) database system used in Japan provides clinical information regarding acute hospital patients. The present study was conducted to determine the association of oral bacterial numbers in individual patients treated at a single institution with length of hospital stay and medical costs using DPC data. A total of 2369 patients referred by the medical department to the dental department at Hiroshima University Hospital were divided into the low (n = 2060) and high (n = 309) oral bacterial number groups. Length of hospital stay and medical costs were compared between the groups, as well as the associations of number of oral bacteria with Charlson comorbidity index (CCI)-related diseases in regard to mortality and disease severity. There was no significant difference in hospital stay length between the low (24.3 ± 24.2 days) and high (22.8 ± 20.1 days) oral bacterial number groups. On the other hand, the daily hospital medical cost in the high group was significantly greater (US$1456.2 ± 1505.7 vs. US$1185.7 ± 1128.6, P < 0.001). Additionally, there was no significant difference in CCI score between the groups, whereas the daily hospital medical costs for patients in the high group treated for cardiovascular disease or malignant tumors were greater than in the low number group (P < 0.05). Multivariate regression analysis was also performed, which showed that oral bacterial number, age, gender, BMI, cardiovascular disease, diabetes, malignant tumor, and hospital stay length were independently associated with daily hospitalization costs. Monitoring and oral care treatment to lower the number of oral bacteria in patients affected by cardiovascular disease or cancer may contribute to reduce hospitalization costs.

Octreotide versus Terlipressin as Adjuvant to Endoscopic Variceal Band Ligation in Bleeding Oesophageal Varices: A Systematic Review and Meta-Analysis

Background: Acute variceal bleeding (AVB) is a critical complication of portal hypertension, contributing significantly to mortality worldwide. Pharmacological interventions, including terlipressin and octreotide, have evolved to manage AVB, yet consensus on their comparative effectiveness remains elusive. This study conducts a comprehensive systematic review and meta-analysis of randomized control trials (RCTs) comparing terlipressin and octreotide in the management of AVB, aiming to provide insights into their relative benefits. Methods: This study included RCTs with head-to-head comparisons of terlipressin and octreotide. The search strategy covered PubMed, Scopus, and Cinahl databases, and the included studies involved adult patients with confirmed AVB undergoing endoscopic variceal band ligation (EVBL). Results: Seven RCTs meeting inclusion criteria were included in the meta-analysis. The assessed outcomes were: achieving haemostasis within 24 h, rebleeding rate, and mortality rate. The pooled analysis revealed no statistically significant differences between terlipressin and octreotide in achieving haemostasis (OR: 1.30, p = 0.23), rebleeding rates at 5 days (OR: 0.7, p = 0.23), and mortality at 42 days (OR: 0.9, p &gt; 0.5). Conclusion: This meta-analysis suggests that terlipressin and octreotide exhibit similar efficacy in reducing bleeding, rebleeding rates, and mortality when used as adjuvants to EVBL in AVB. Clinicians are encouraged to consider individual patient characteristics and the broader clinical context when choosing between these agents. Future research should focus on addressing existing evidence gaps and enhancing understanding of variables influencing EVBL outcomes.

Regional Comprehensive Care for People with Mental Disorders - An Opportunity for Transparency and Innovative Evaluation

Against the background of the discussion about a comprehensive regional mental health care service, the essay discusses the possibility of a comprehensive, transparent and meaningful evaluation. Proposals for how structures, processes, and outcomes may be assessed are presented. We argue for collecting data that are transparent and actionable on all levels of care organisations. The suggested evaluation would be innovative, meaningful for individual patients, services, health care organisations and whole regions, and thus a way for a data-driven ongoing quality improvement.

AMPLITUDE EQUATIONS AND ORDER PARAMETERS OF HUMAN SARS-COV-2 INFECTIONS AND IMMUNE REACTIONS: A MODEL-BASED APPROACH

Several recent modeling studies have attempted to understand the human immune reaction to SARS-CoV-2 infections. Such a model-based understanding provides a sound basis for fighting COVID-19 on the level of individual patients. However, in this context, a worked-out nonlinear physics analysis providing insights into underlying amplitude equations and potential COVID-19 order parameters has not been conducted so far. In order to conduct such an analysis, a three-variable virus dynamics model is considered that can account for the human immune reaction to SARS-CoV-2 infections. The model amplitudes equations are derived and the relevant order parameter is determined. In line with theoretical reasoning, it is demonstrated that the order parameter and its amplitude determine the initial stage of SARS-CoV-2 infections, in general, and the initial dynamics of immune reactions, in particular. Explicitly, this finding is demonstrated for data from four COVID-19 patients. For those patients it is also demonstrated that the remnant of the order parameter determines the final disease decline phase. In this context, a time-resolved eigenvalue analysis is conducted that reveals that the transition from the initial stage to the decline stage which is associated with a switch of the leading eigenvalue from a positive to a negative value. It is argued that the immune reaction essentially contributes to this switch. From a medical-physics point of view, this observation suggests that the immune reaction of COVID-19 patients can stabilize the virus-free fixed point of affected sites.

Prostate cancer biomarkers: from early diagnosis to precision treatment.

Prostate cancer (PCa) is the second most prevalent cancer in men. In 2020, approximately 1,414,259 new cases were reported that accounted for 3,75,324 deaths (Sung et al. in CA 71:209-249, 2021). PCa is often asymptomatic at early stages; hence, routine screening and monitoring based on reliable biomarkers is crucial for early detection and assessment of cancer progression. Early diagnosis of disease is key step in reducing PCa-induced mortality. Biomarkers such as PSA have played vital role in reducing recent PCa deaths. Recent research has identified many other biomarkers and also refined PSA-based tests for non-invasive diagnosis of PCa in patients. Despite progress in screening methods, an important issue that influences treatment is heterogeneity of the cancer in different individuals, necessitating personalized treatment. Currently, focus is to identify biomarkers that can accurately diagnose PCa at early stage, indicate the stage of the disease, metastatic nature and chances of survival based on individual patient profile (Fig.1). Fig.1 Graphical abstract.