Invasive ductal carcinoma (IDC) shows marked heterogeneity in clinical outcomes, often not fully captured by standard molecular subtypes. Tumor mutational burden (TMB) has limited prognostic utility in IDC due to low mutation rates and failure to account for structural genomic alterations. Fraction genome altered (FGA), reflecting copy number changes, may better represent genomic instability and disease aggressiveness. We analyzed 3396 IDC patients from the AACR GENIE cohort, focusing on four key gene mutations (TP53, PIK3CA, GATA3, MAP3K1). Machine learning models (logistic regression and support vector machine) were trained using FGA or TMB as the main predictors, adjusted for clinical variables, to predict mortality. Fraction genome altered consistently outperformed TMB in mortality prediction across all gene subtypes. In TP53-mutated patients, FGA improved the area under the receiver operating characteristic curve (AUROC; 0.70 vs. 0.69) and accuracy (67
A 66-year-old male without long-term medication presented with painless jaundice, itching, clay-colored stools, and concentrated urine. Laboratory findings showed elevated bilirubin (15.6 mg/dL, direct bilirubin 13.4 mg/dL) and liver enzymes (GOT 95 U/L, GPT 137 U/L, gamma-GT 65 U/L, normal alkaline phosphatase). Transient elastography found increased liver stiffness (11.5 kPa) and mild steatosis (Controlled Attenuation Parameter, CAP: 240). Abnormal sexual hormone tests and detailed medical history revealed the use of selective androgen receptor modulators (SARMs; ostarine and testolone) and other performance-enhancing drugs (PEDs; cardarine). All substances were acquired online, are prohibited by the World Anti-Doping Agency, and are not approved as drugs. Probable substance-induced liver injury was reported to the authorities, who initiated forensic investigations. Chemical analysis showed dosages exceeding regulatory thresholds. The pharmacovigilance report enabled legal actions and further contributed to international law enforcement operations. Our case report describes the hepatotoxic risks of SARMs/PEDs and highlights the importance of pharmacovigilance reporting to facilitate forensic and regulatory anti-doping implications.
Increasing antimicrobial resistance has become a major challenge in the treatment of Helicobacter pylori infection. Sulforaphane, a bioactive isothiocyanate derived from broccoli sprouts, has demonstrated anti-H. pylori activity in experimental and clinical studies. Curcumin and probiotic bacteria have also been investigated as adjunctive therapies. A woman in her seventies underwent upper gastrointestinal endoscopy screening. Histology revealed chronic active Helicobacter pylori-associated gastritis involving the antrum and corpus. Molecular testing confirmed H. pylori infection and detected the clarithromycin resistance mutation A2143G in the 23S rRNA gene. Following treatment with bismuth quadruple therapy consisting of Pylera® (Laboratoires Juvise Pharmaceuticals, France: bismuth subcitrate potassium 140 mg, metronidazole 125 mg and tetracycline hydrochloride 125 mg per capsule; three capsules four times daily) plus pantoprazole (40 mg twice daily for 10 days, followed by pantoprazole 40 mg once daily for 4 weeks), repeat endoscopy 1 year later demonstrated persistent active gastritis and persistence of the resistance mutation. The patient subsequently received a nutraceutical preparation containing broccoli-derived sulforaphane, curcumin, and Lactobacillus acidophilus. The preparation was administered as two capsules twice daily before meals for 21 days. Follow-up endoscopy approximately 3 months later demonstrated resolution of inflammatory activity and the absence of detectable H. pylori organisms in antral and corpus biopsies. This case documents the histological disappearance of persistent clarithromycin-resistant H. pylori infection following administration of a sulforaphane-, curcumin- and probiotic-containing nutraceutical. Although causality cannot be established from a single observation, the findings support further investigation of such interventions in patients with treatment-refractory infection.
Extracorporeal shockwave therapy (ESWT) was initially used for urologic issues only. After Valchanou and Michailov started applying it in orthopedics in 1991, they focused on treatment of pseudarthrosis and delayed fracture healing. Some years later, shockwave therapy was also used for tendinopathies. Today, ESWT is the first-choice treatment for tendinopathies and is unsurpassed in terms of effectivity and side effects. This article discusses common regions of lower extremity tendinopathies (greater trochanter pain syndrome, quadriceps tendinopathy, patellar tendinopathy, Achilles tendinopathy) in a narrative review of the evidence-based literature and guidelines of leading shockwave societies such as the International Society for Medical Shockwave Treatment (ISMST) and the Deutschsprachige internationale Gesellschaft für Extrakorporale Stosswellentherapie (DIGEST). Additional case studies are also presented. Extracorporeal shockwave therapy shows excellent results in the evidence-based literature and in clinical application. No other conservative treatment option in orthopedics is described as intensively in the evidence-based literature as shockwave therapy. ESWT seems to be more effective when it is accompanied by an eccentric loading/physiotherapy program. Extracorporeal shockwave therapy enables tendon regeneration, long-term improvement, and faster return to sport, with predictable side effects and excellent tolerance.
Sepsis-associated encephalopathy (SAE) is a complex neuroinflammatory condition characterized by diffuse brain dysfunction arising from systemic infection without direct central nervous system invasion. In modern critical care, device-associated infections (DAIs) caused by invasive medical devices, such as central line-associated bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections, have become critical drivers of intensive care unit (ICU)-acquired sepsis. Biofilm formation on these devices establishes persistent inflammatory reservoirs that continuously shed microorganisms, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs) into the circulation, sustaining systemic immune activation. This review outlines an integrated mechanistic framework linking DAIs to acute brain dysfunction. Systemic inflammation and endothelial activation trigger microvascular dysfunction, impaired cerebral autoregulation, and blood–brain barrier disruption. These peripheral vascular alterations allow inflammatory mediators to access the central nervous system, where they induce microglial and astrocytic reactivity. Persistent neuroimmune activation compromises neurotransmitter homeostasis—causing glutamate excitotoxicity and cholinergic deficits—while impairing neuronal mitochondrial oxidative phosphorylation. The resulting oxidative stress, energy failure, and self-amplifying neuroinflammatory feedback loops culminate in synaptic damage and neuronal injury. Clinically, this manifests as altered consciousness, delirium, seizures, and long-term neurocognitive impairment. By framing SAE as a concurrent, multidimensional continuum rather than a linear sequence, this review highlights the critical role of early infection prevention, timely device removal, and targeted neuroprotective strategies aimed at stabilizing vascular integrity and mitigating neuroinflammation.
