Abstract: Background/Objectives: Sepsis detection remains challenging due to clinical heterogene-ity and limitations of traditional scoring systems. This study developed and validated a hospital-wide machine learning model for sepsis detection using retrospectively devel-oped data from prospectively expert-validated cases, aiming to improve diagnostic accu-racy beyond conventional approaches. Methods: This retrospective cohort study analyzed 218,715 hospital episodes (2014-2018) at a tertiary care center. Sepsis cases (n=11,864, 5.42%) were prospectively validated in real-time by a Multidisciplinary Sepsis Unit using modified Sepsis-2 criteria with organ dysfunction. The model integrated structured data (26.95%) and unstructured clinical notes (73.04%) extracted via natural language pro-cessing from 2,829 variables, selecting 230 relevant predictors. Thirty models including random forests, support vector machines, neural networks, and gradient boosting were developed and evaluated. The dataset was randomly split (5/7 training, 2/7 testing) with preserved patient-level independence. Results: The BiAlert Sepsis model (random forest + Sepsis-2 ensemble) achieved AUC-ROC 0.95, sensitivity 0.93, and specificity 0.84, signifi-cantly outperforming traditional approaches. Compared to the best rule-based method (Sepsis-2 + qSOFA, AUC-ROC 0.90), BiAlert reduced false positives by 39.6% (13.10% vs 21.70%, p< 0.01). Novel predictors included eosinopenia and hypoalbuminemia, while traditional variables (MAP, GCS, platelets) showed minimal univariate association. The model received European Medicines Agency approval as a medical device in June 2024. Conclusions: This hospital-wide machine learning model, trained on prospectively ex-pert-validated cases and integrating extensive NLP-derived features, demonstrates supe-rior sepsis detection performance compared to conventional scoring systems. External validation and prospective clinical impact studies are needed before widespread imple-mentation.

Abstract: Objective: To provide the first nationwide description of biologic and targeted synthetic DMARD (b/tsDMARD) use among Estonian patients with rheumatoid arthritis (RA), focusing on treatment effectiveness, persistence, and reasons for discontinuation across sequential lines of therapy. Methods: Data were obtained from the Estonian Biologic Therapy Registry covering years 2006–2022. All adult RA patients (ICD-10 M05.8, M06.0) who had received at least one dose of a b/tsDMARD were included. Effectiveness at 6 months was evaluated using DAS28-CRP as a continuous measure (ΔDAS28) and categorical response definitions: remission (DAS28 ≤2.6), low disease activity (LDA ≤3.2), and EULAR response criteria. Treatment persistence was analyzed using Kaplan–Meier estimates, and reasons for discontinuation were categorized systematically. Results: A total of 1,074 patients were analysed (78% female, mean age 53.7 years, 86% sero-positive). Mean baseline DAS28-CRP was 5.3. The mean 6-month reduction in DAS28-CRP during first-line therapy was ~2.3 points. Remission was achieved in ~20% of patients in lines 1–3 and ~15% in later lines, while LDA occurred in 7–10% across lines 1–4. Drug survival was comparable between treatment lines: 60% of patients remained on therapy at 2 years, and the median time to discontinuation for first-line therapy was 1.66 years. Most patients initiated therapy with a TNF inhibitor and many continued within the same class before switching to IL-6 inhibitors, rituximab, or JAK inhibitors. The main reasons for discontinuation were loss or lack of efficacy (~50%) and adverse events (27.5%), predominantly allergic reactions and infections. Conclusions: In real-world Estonian RA practice, biologic and targeted therapies were effective across multiple treatment lines, with the greatest improvement observed during first-line therapy and sustained clinical benefit in later lines. Treatment persistence remained stable despite multiple switches, and the distribution of discontinuation causes mirrored other European registries. These findings support the continued value of sequential b/tsDMARD therapy in achieving disease control among patients with difficult-to-treat RA.

Abstract: Vaccine safety concerns place informed parents into a dilemma: Take the risk of preventable illnesses by refusing vaccines or risk autism by complying with the vaccine schedule. This query sought a resolution by identifying susceptibility factors to intoxication by aluminium, a suspect component used in some vaccines as adjuvants. A systematic review reconciles that although aluminium decreases parathyroid hormone (PTH) secretion, hyperparathyroidism (hPTH) causes susceptibility to aluminium intoxication. The review results incidentally supported a hypothesis explaining the male-biased gender ratio. Thus, a narrative review seemed appropriate on proceeding. Susceptibility extends beyond chronic kidney disease (CKD) to conditions where hypophosphatemia is mediated by hPTH and efficient aluminium excretion is impaired by renal tubular reabsorption. Aluminium intoxication is marked by hypophosphatemia. Thus, individuals with underlying hypophosphatemic tendencies are less able to tolerate aluminium burden. PTH drives aluminium to tissues such as bone and brain as if it were calcium. The male gender bias is explained by a more limited supply of PHEX enzyme (expressed on the X chromosome) that limits phosphate wasting. These findings might imply that aluminium toxicity is sufficient to cause autism. Research is indicated to develop standards for pre-vaccination screening and intervention of conditions that impair aluminium excretion.

Abstract: AI and ML in spine surgery has both transformative possibilities and notable challenges related to regulatory oversight, algorithmic bias, and clinical responsibility. We propose a governance model to tackle these important issues, ensuring the responsible use of AI tools. This framework introduces the SAIGE-R Index, a tool designed to measure AI system risks based on Clinical Volatility, System Integration Risk, and Data Integrity Confidence. This index supports a tiered oversight system, ranging from minimal checks for low-risk systems to thorough FDA reviews for high-risk applications. In addition, SAIGE sets specific validation standards focused on spine surgery outcomes. These include important differences in patient-reported measures and accuracy in pedicle screw placement, along with quarterly fairness checks to reduce demographic bias. The framework also describes a strong governance structure that focuses on ongoing clinician training, involvement from multiple stakeholders, and strict data security measures. It suggests a liability model that matches responsibility with the evaluated risk level of AI tools. By addressing validation, ethics, and accountability, the SAIGE Framework provides a foundation for safely and effectively incorporating AI into complex surgical settings. This approach encourages innovation while maintaining patient safety and clinical integrity.

Abstract: Sepsis initiates two primary metabolic responses: insulin resistance in insulin-responsive tissues and suppression of mitochondrial adenosine triphosphate (ATP) production. These mechanisms underpin the hypermetabolic and hypometabolic phases of sepsis. The hypermetabolic phase features a heightened metabolic rate, rapid immune activation, and increased glucose supply and consumption. In contrast, the hypometabolic phase involves a reduction in metabolic rate and physiological activity across multiple organs, mirroring hibernation-like states.During sepsis, the immune system receives priority access to available glucose, prompting insulin resistance that minimises glucose utilisation by less essential tissues. Concurrently, mitochondrial ATP production via oxidative phosphorylation (OXPHOS) is deprioritised, with the immune system relying on anaerobic glycolysis for ATP generation. This suppression of OXPHOS is only a temporary measure; mitochondrial ATP production must resume for complete recovery. Persistent suppression of mitochondrial ATP production can culminate in critical ATP deficits and cell death.This review examines glucose and insulin metabolism in sepsis, concluding that administering high-dose insulin alongside mild hyperglycaemia and intravenous thiamine—a pyruvate dehydrogenase kinase (PDK) inhibitor—may help restore physiological mitochondrial ATP production during a crucial window in the sepsis process, potentially improving survival outcomes.

Abstract: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has emerged as a rapidly expanding global clinical challenge, closely intertwined with obesity, type 2 diabetes mellitus, chronic kidney disease, and cardiovascular complications. Given the convergence of metabolic, hepatic and cardiac pathways, an integrated clinical strategy is increasingly essential. This review highlights how coordinated management across various specialties can refine risk stratification, improve diagnostic accuracy, and enhance long-term outcomes for patients with MASLD. The growing epidemiological burden is paralleled by escalating risks of heart failure, arrhythmias and progressive liver injury. Shared mechanisms including insulin resistance, systemic inflammation and lipotoxicity reinforce the need for comprehensive evaluations using non-invasive fibrosis scores, cardiometabolic biomarkers and structured surveillance protocols. Evidence supports the incorporation of lifestyle interventions, GLP-1 receptor agonists, SGLT2 inhibitors and tailored cardiometabolic monitoring within multidisciplinary clinics. Despite barriers such as heterogeneous referral patterns and limited cross-specialty coordination, interdisciplinary models consistently demonstrate superior early detection and more precise therapeutic planning. Moving forward, standardized follow-up pathways, longitudinal risk-based surveillance, and AI-assisted prediction tools may substantially improve personalized care and reduce morbidity in this high-risk population.

Abstract: As a three-dimensional in vitro model, organoid technology represents a revolutionary breakthrough in precision medicine. By harnessing the self-organizing capabilities of stem cells within biomimetic extracellular matrices, it enables the generation of miniature tissues that recapitulate key structural and functional characteristics of their source organs[1]. Conventional two-dimensional cell cultures lack tissue architecture and microenvironmental cues, whereas animal models are hindered by interspecies differences and inadequate representation of human pathological heterogeneity[2]. By effectively addressing these limitations, organoids have emerged as powerful platforms that are highly representative of human physiology and disease processes in oncology, genetic disorders, and infectious diseases. They demonstrate significant potential for use in drug screening, toxicity assessment, and the development of personalized treatment strategies[3, 4]. Although challenges such as limited vascularization, lack of standardized culture protocols, and ethical considerations remain, the integration of multidisciplinary approaches such as AI-assisted analysis, organ-on-a-chip systems, and 3D bioprinting, together with increasing policy support and industrial advancement, is accelerating the clinical translation of organoid technology[5]. In this review, the construction strategies for and applications of organoid models are systematically summarized, and their value and limitations in disease modeling, precision medicine, and preclinical research is highlighted. Finally, future development pathways driven by multidisciplinary collaboration and standardization are outlined.

Abstract:

Background: Hyperuricemia, marked by elevated uric acid levels, is associated with renal disorders like acute kidney injury and chronic kidney disease, through both crystal-dependent and crystal-independent mechanisms. Objective: This review aims to evaluate the crystal-dependent and crystal-independent mechanisms by which hyperuricemia induces renal injury. Design: A systematic review of the literature. Participants: Human and animal studies. Measurements: A total of 1549 articles were initially identified from PubMed, Web of Science, Scopus, and Google Scholar. After removing 659 duplicates and screening titles and abstracts, 572 articles were excluded, and 16 could not be retrieved, leaving 302 for full-text review. Of these, 17 studies met the eligibility criteria and were included. Risk of bias was assessed using SYRCLE for animal studies, ROB2 for human studies, and NOS for observational studies. Results: From seventeen studies: nine animal experiments, one human experiment, and seven observational studies. Animal studies showed hyperuricemia causes preglomerular arteriolopathy, glomerular hypertension, and worsens nephrotoxicity. Human studies demonstrated elevated uric acid, even without crystals, activates intrarenal RAS, increases oxidative stress, and reduces nitric oxide. Clinical studies confirmed high uric acid is linked to CKD progression, with very low levels also risky (“J-shaped” relationship). Endothelial dysfunction is a unifying mechanism, promoting inflammation and fibrosis in crystal-dependent injury and vasoconstriction and renal damage in crystal-independent injury. Conclusions: This review confirmed that hyperuricemia damages the kidney through both crystal-dependent and crystal-independent pathways, with endothelial dysfunction as a key mediator. Further human studies are needed to confirm these findings and explore new treatments.

Abstract: Background Chronic post-stroke spasticity often limits gait despite best-practice botulinum-toxin intramuscular injections (BTI), whose benefit is constrained by short duration, dose ceilings and tachyphylaxis. Cryoneurolysis (CNL) induces a reversible axonotmesis with preserved endoneurium, potentially providing longer tone reduction with fewer adverse effects, but its impact on whole-gait quality and its compatibility with implanted functional electrical stimulation (FES) remain poorly documented. Case presentation A 43-year-old man, 12 years after right middle cerebral artery stroke, walked independently with an implanted common peroneal FES system but complained of effortful gait with left-knee “locking” and drop foot without FES. Multiple BTI series to triceps surae and quadriceps yielded only transient benefit. Two ultrasound-guided CNL sessions targeted tibial (soleus, medial gastrocnemius) and femoral (rectus femoris, vastus intermedius) motor branches. Quantitative gait analysis and fine-wire electromyography (EMG) were performed at baseline, 6 weeks after each CNL, and 6 months, with and without FES. CNL produced immediate and sustained reductions in triceps surae and quadriceps overactivity, resolution of genu recurvatum, normalization of stiff-knee gait, improved ankle dorsiflexion, and increased swing-phase knee flexion (>50°). Gait Deviation Index rose from 69 to 80 and Gillette Gait Index decreased by more than 50%, with preserved strength and no adverse events. Conclusions Targeted, sequential CNL of tibial and femoral motor branches can safely deliver durable, clinically meaningful gait improvements when BTI has reached its ceiling and can act synergistically with implanted FES. Quantitative gait analysis and EMG sharpen clinical decision-making in spasticity management.

Abstract: Background/Objectives: Endoscopic biliary stenting is the standard palliative intervention for malignant biliary obstruction, aimed at restoring ductal patency. Radiofrequency ablation (RFA) has been introduced as an adjunct technique to improve stent durability and patient outcomes. However, the literature remains inconclusive regarding which patients are most likely to benefit from the combination of RFA and stenting. Methods: To assess clinical outcomes of patients undergoing RFA with biliary stenting and identify the factors associated with treatment success, clinical data were collected from 24 patients suffering from non-resectable malignancies. Post-procedural and 6-month follow-up clinical success and complication rates were measured by the technical success of RFA and a decrease in blood bilirubin levels. Results: Nineteen females and five males were included in the study. The most prevalent diagnoses were metastatic adenocarcinoma (n = 8) and cholangiocarcinoma (n = 6). 25% of patients did not complete the 6-month follow-up due to malignancy progression. 16 out of 18 maintained the patency of biliary stents and were able to continue the oncological treatment. The two patients required multiple unsuccessful endoscopic interventions. Conclusions: RFA with biliary stenting is a very effective, safe method for maintaining biliary patency in cases of unresectable biliary malignant obstruction. While we did not identify any specific factors associated with treatment success or failure, our findings support the use of RFA with biliary stenting as a safe, feasible option in non-resectable malignancies of the biliary tract.

Abstract: The successful use of bromhexine hydrochloride (BRH) for COVID-19 prevention led us to apply the same method for flu prevention. The goal of this study is to observe whether BRH could protect people against influenza.This is non-interventional, observational, questionnaire-based survey. General practitioners informed their patients to take BRH 8 mg twice per day for at least 3 weeks if they want. The mean participant age was 58.9 years (95% CI: 57.4–60.5), with a median of 62 years, indicating that the sample predominantly consisted of individuals over 60 years of age.The average number of comorbidities was 0.98, and the mean duration of prophylactic use was 80 days (95% CI: 76.7–83.7). The reported influenza incidence within the sample was 10.6%.Influenza incidence among individuals taking BRH prophylactically was significantly lower compared to national data (36.15%). Longer use was associated with a modest reduction in risk. The number of comorbidities remained the strongest predictor of influenza occurrence. Age had no significant impact among those using BRH prophylactically. The model demonstrated good discriminative ability but limited calibration, and the results should be interpreted cautiously.

Abstract: Background/objectives: Psoriatic disease (PsD) encompasses psoriasis (PsO) and psori-atic arthritis (PsA) and is associated with heterogeneous cardiometabolic risk. Inte-grating immunogenetic markers such as HLA-Cw6 into data-driven analyses may re-fine phenotyping and uncover clinically meaningful endotypes. We aimed to identify cardiometabolic phenotypes across PsD, integrating HLA-Cw6 and exploring dis-ease-specific heterogeneity and predictors of high-risk profiles. Methods: In a cross-sectional study of 572 PsD patients (401 PsO, 171 PsA), eight demographic and clinical variables including HLA-Cw6 were entered into k-means clustering (k = 4). Cardiometabolic risk factors were profiled post hoc. Cluster validity was assessed by Gaussian Mixture Models and principal component analysis (PCA). Stratified analyses (k = 3) were conducted separately for PsO and PsA. Predictors of the high-risk pheno-type were examined using bootstrap-resampled logistic regression. Results: Four global clusters were identified, ranging from inflammation-dominant/low-risk to a small high-risk group (C4, 5.8 %). C4 combined older age (median 66 years) with universal CVD and the highest prevalence of hypertension (75.8 %) and dyslipidemia (69.7 %). PCA confirmed two dominant orthogonal axes: cardiometabolic and inflammato-ry/immunogenetic. Validation showed high concordance (adjusted Rand index 0.83). In stratified analyses, HLA-Cw6 showed opposite associations—enriched in high-risk PsO (OR 2.0, 95 % CI 1.3–3.1) but depleted in high-risk PsA (OR 0.24, 95 % CI 0.11–0.52). Conclusions: Incorporating HLA-Cw6 into clustering identified reproducible cardiometabolic phenotypes with distinct genetic signatures. The inverse HLA Cw6–risk patterns in PsO and PsA suggest disease-specific endotypes with differing cardi-ometabolic trajectories, supporting genetic–clinical integration for targeted prevention.

Abstract: In parametric statistical analysis, the independent-samples t-test is a widely used method for comparing the means of two different groups. Under the assumption of homogeneity of variances and normally distributed data, it evaluates the statistical significance of observed differences between group means. The fundamental ideas of the independent-samples t-test—including its assumptions, hypotheses, effect size considerations, and methodological applications in research—are investigated in this review. Furthermore, fundamental methodological issues, including the interpretation of statistical significance, are covered. Aiming to increase researchers' competency in using and interpreting the independent-samples t-test across studies, this paper provides a thorough tutorial on the test. In addition, this review highlights JASP (Jeffrey’s Amazing Statistics Program), an open-source statistical platform with an interface for conducting independent-samples t-tests. JASP provides automated assumption checks, effect size calculations, and graphical outputs, making it accessible for researchers with varying levels of statistical expertise.

Abstract: Background: Endometriosis is a chronic inflammatory disorder affecting about 190 million women of reproductive age worldwide. It represents a major health challenge due to its broad impact on physical, reproductive, and psychological well-being and is clinically characterized by pelvic pain, menstrual irregularities, and infertility. Methods: This narrative review synthesized current evidence on the relationship between adiposity, metabolic and inflammatory markers, and endometriosis from a biopsychosocial and intersectional perspective. A comprehensive search was conducted in PubMed, Scopus, and Web of Science for peer-reviewed studies published in English over the past decade. Results: Endometriosis significantly affects inflammatory activity within adipose tissue, in especial in visceral adipose tissue. Studies also reported reduced adipocyte size and altered adipose tissue function. The endometriosis cytokine profile exhibited a pattern of systemic and tissue-specific inflammatory activation (i.e., elevated levels of interleukin-6 and monocyte chemoattractant protein-1). Sociodemographic factors (i.e., age, race/ethnicity, socioeconomic status, and educational level) also play a significant role in differences in symptomatology, disease course, and healthcare access. Conclusions: Endometriosis need to be considered as a multisystem condition related to metabolic, inflammatory, and psychosocial factors. It is necessary to adopt a biopsychosocial and intersectional perspective to improve diagnosis and support more equitable and personalized therapeutic approaches.

Abstract: This extensive narrative analysis investigates the complex and diverse aspects of patient experience within the healthcare system, placing notable attention on the frequently unrecognized roles of non-clinical employees. The review commences by delineating the conceptual and theoretical underpinnings, encompassing frameworks of patient-centered care, Donabedian’s structure–process–outcome model, and experience-based co-design, to elucidate how both clinical and non-clinical interactions collaboratively influence outcomes such as patient satisfaction, trust, and adherence to treatment protocols. The report describes the transformation of the discipline throughout history, focusing on the amplified recognition of administrative and support personnel in improving patient interactions. Contemporary movements illustrate a flourishing blend of electronic feedback systems, an enhanced deployment of patient experience metrics, and an elevated attention to equity, dialogue, and organizational values. Critical assessments underscore persistent shortcomings, particularly the limited empirical research concerning non-clinical contributions and the inadequate implementation of feedback mechanisms in quality improvement initiatives. The aforementioned limitations are particularly pronounced in low- and middle-income nations, where empirical investigations remain limited despite the significant potential influence of non-clinical personnel on patient experiences within resource-constrained healthcare systems. Practical uses are demonstrated through learning initiatives, consistent tracking, and reward frameworks that help both medical and non-medical teams in boosting the quality-of-service delivery. The review demonstrates that a holistic strategy directed at patient experience demands acknowledgment of how clinical, administrative, and environmental factors are interconnected. Future trajectories encompass an enhanced amalgamation of technologically-mediated feedback, customized professional development for personnel, and a methodical incorporation of non-clinical viewpoints within patient-centric frameworks. This examination reveals the significant requirement for health care systems to diversify their selection of enhancement techniques to foster trust, engagement, and patient compliance.

Abstract:

Background/Objectives: Chronic pudendal neuralgia is a relatively rare condition in the general population, with an incidence of 1%. Although diagnosis of pudendal neuralgia is mainly clinical, Magnetic Resonance Imaging (MRI) is commonly performed to obtain further information. However, clear criteria and guidelines to MRI diagnosis and clinical-radiological correlation are still not definite. Methods: We reviewed 81 patients with chronic pudendal neuralgia, studied by MRI designed protocol for pelvis and pelvic floor examination. A key element of the protocol was the application of a sequence Axial EPI b0,100,600 for a neurographic evaluation of the nerve. Results: MRI examination revealed DWI abnormalities in 42/81 patients. Pudendal nerve abnormalities were unilateral in 33/42 patients and bilateral in 9/42. Moreover, in 23/42 patients, pathologies related with high probability to the neuropathy have been identified. Conclusions: This study highlights the diagnostic potential of MRI in patients with chronic pudendal neuralgia. The authors suggest MRI criteria to increase reproducibility and confidence in pudendal neuropathy diagnosis.

Abstract:

Background: A subset of individuals develops persistent symptoms following SARS-CoV-2 infection, including musculoskeletal (MSK) manifestations, a condition known as long COVID (LC). Emerging hypotheses suggest that chronic low-grade inflammation in LC may impair bone metabolism and compromise joint health. However, empirical evidence is limited, and the impact of LC on MSK health, particularly bone and joint integrity, is poorly understood. Aim: To determine the influence of LC on MSK function, including bone health, body composition, and joint integrity. Methods: A 12-month longitudinal prospective cohort feasibility study was conducted involving 45 adults with LC and 40 well-recovered (WR) post-COVID-19 controls. Baseline and follow-up assessments included dual-energy X-ray absorptiometry (DXA) for bone mineral density (BMD) and total body composition (TBC), alongside ultrasound of the hand and knee joints to evaluate intra-articular changes. Results: The LC group had more fat in the gynoid, android, and leg regions at each assessment point compared to the controls (p<0.01). LC showed a significantly lower synovial hypertrophy at the baseline, 13% compared to WR 45% (p=0.001), and a marginal improvement in hand synovial hypertrophy, over 12 months, from a median of 2 (IQR 1;5) to 1 (IQR 0;3) (p=0.012), as observed via MSK ultrasound. No notable differences were found between groups regarding BMD, either in the LC group compared to the control group or overtime. Conclusion: This cohort study of LC adults and controls found no evidence of rapid bone loss; however, adiposity and joint symptoms suggest the need for ongoing monitoring. Future research should focus on MSK markers, muscle function, advanced imaging, and improving MSK health.

Abstract: Background: Avascular wounds represent a significant challenge in medical care due to impaired blood flow. Synthetic matrices, such as poly-lactic acid (PLA), have demonstrated promising results in promoting wound healing in complex wounds, including those with restricted blood supply, such as diabetic foot and venous leg ulcers. Objective: This case series presents the outcomes of five patients with avascular wounds of various etiologies successfully treated with PLA matrices. Case description: Five patients presented complex wounds involving exposure of bone, tendon, fascia, or osteosynthetic material. Wound bed preparation included debridement followed by PLA application covered with additional layers (non-adherent dressing, absorbent dressing, and compression bandage) as needed. Weekly assessments were conducted until full wound closure was achieved. Results: All cases showed successful outcomes, with PLA promoting granulation tissue formation and re-epithelialization, contributing to wound closure. One patient required skin grafts for complete healing. No local infections were reported before or after PLA application. Conclusion: PLA matrices are a practical and effective option for managing complex avascular wounds, promoting tissue regeneration and optimizing wound bed quality for skin grafts or flaps. While these findings are promising, further studies are needed to confirm the broader applicability and efficacy of PLA in avascular wound management.

Abstract: Physiological and psychological resilience has important implications for health, disease and treatment. Resilience is shown to boost treatment compliance as well as response and thereby reduce mortality. We consider the possibility that individuals having lower resilience are more likely to discontinue treatment in response to side effects of a drug. In randomized control trials (RCT) if a considerable proportion of individuals discontinue from the treatment group because of side effects, the average resilience in the remaining treatment group would be greater. As a result, the frequency or severity of adverse outcomes in the treatment group will be smaller than the control even when the drug has no effect. This bias is more likely to be serious for drugs with more frequent and/or serious side effects, but following intention to treat (ITT) protocols with some additional precautions can help in avoiding it. We suggest testable predictions of the resilience selection bias hypothesis along with ways to quantify and correct for the bias in RCTs. Attempts to detect, measure and correct for the resilience selection bias should be considered necessary for realistic evaluation of drug action in a clinical trial. Retrospective studies are more sensitive to RS bias than RCTs and need to be interpreted carefully.

Abstract:

Photobiomodulation (PBM) has ancient origins being Hippocrates considered the first physician who recommended to expose ulcers and wounds to sunlight for accelerating the healing process. Subsequently, at the end of the 18^th century, Joseph Priestley started his photochemical rechearses, later continued by Antoine de Lavoisier who constructed the basis of modern photobiology. In 1960 Theodore Maima constructed the first laser device emitting a coherent, collimated and monochromatic (red) beam and Andre Mester, few years after, discovered the possibility to use the coherent light at low power to increase the wound healing process. Konstantin Korotov, between the 1980s and the first decade of the 2000s, realized the bioelectrographic GDV (Gas Discharge Visualization) device, a particular kind of camera able to detect and measure the energy fields inside the body. The aim of this brief report is to describe the opportunities of the PBM in the human body, both for diagnostic and therapeutical utilization.