Insulin resistance (IR) is a prevalent metabolic condition characterized by reduced cellular responsiveness to insulin and consequent hyperinsulinemia, and it is a key component of type 2 diabetes and metabolic syndrome. A growing body of evidence suggests IR is a critical accomplice in the pathogenesis of various cancers. This review synthesizes evidence on underlying molecular mechanisms, including the integrated roles of the insulin/IGF system, chronic inflammation, metabolic reprogramming, and mitochondrial dysfunction. This review proposes that metabolic dysregulation should be viewed as a modifiable oncogenic force. This perspective illuminates new pathways for understanding cancer development and offers promising avenues for prevention and therapeutic intervention.

Introduction and importance: Pulmonary mucormycosis (PM) is a severe fungal infection threatening immunocompromised individuals, especially with uncontrolled diabetes. Co-infection with bacteria like Achromobacter xylosoxidans complicates management. We report a rare and fatal case of PM co-infected with A. xylosoxidans , which was further complicated by a subsequent SARS-CoV-2 superinfection. Case presentation: A 55-year-old female with poorly controlled type 2 diabetes mellitus and multiple comorbidities presented with worsening dyspnea. Investigations revealed severe hyperglycemia (927 mg/dL), hyponatremia, and imaging showed a large right upper lobe cavitary lesion. Bronchoscopy confirmed acute necrotizing pneumonia with Zygomycetes (Mucor) elements and grew >100 000 CFU/mL A. xylosoxidans/denitrificans . Computed tomography also revealed extensive nasopharyngeal mucormycosis. Her hospital course was complicated by a hyperosmolar hyperglycemic state, pulseless electrical activity cardiac arrest secondary to hemoptysis, and a subsequent SARS-CoV-2 superinfection, ultimately resulting in death. Clinical discussion: This case exemplifies the diagnostic difficulties of PM, often mimicking other pulmonary conditions and requiring invasive testing for confirmation. Uncontrolled diabetes was a critical predisposing factor. The presence of A. xylosoxidans , an intrinsically resistant bacterium, alongside PM created significant therapeutic hurdles. The subsequent SARS-CoV-2 superinfection likely further compromised the patient’s critical status. The subsequent SARS-CoV-2 infection likely further compromised the patient’s status. The case underscores the lethal synergy of these sequential opportunistic infections, and the poor prognosis associated with PM, especially when compounded by critical illness and co-infections. Conclusion: High suspicion for invasive fungal infections is crucial in high-risk patients with refractory pneumonia. Prompt invasive diagnostics and awareness of bacterial co-pathogens are essential, as outcomes remain poor despite aggressive therapy.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder primarily affecting joints. Methotrexate (MTX) and hydroxychloroquine (HCQ) are common disease-modifying antirheumatic drugs, yet more comparative outcome studies are needed. This study aimed to compare associations of HCQ versus MTX initiation with mortality, cardiovascular events, and other major health outcomes in RA patients. This retrospective cohort study utilized the TriNetX database (electronic health records from 142 global health care organizations) to compare selected 10-year outcomes in RA patients starting HCQ or MTX therapy. Methods: Patients aged 18–75 years diagnosed with RA (ICD-10 codes) were studied. This retrospective, multi-center cohort study used data from the TriNetX Research Network (analysis: 23 March 2025). Two cohorts, HCQ initiators and MTX initiators, were created. Propensity score matching (PSM) balanced cohorts for age, sex, race, pre-specified comorbidities, and concomitant medications. Primary outcomes were 10-year cumulative incidences of all-cause mortality, non-ST elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI), pulmonary hypertension (PAH), end-stage renal disease (ESRD), interstitial lung disease (ILD), osteoporosis, and Alzheimer’s dementia. Results: After PSM, 56 362 patients were in each cohort. HCQ initiation was associated with significantly higher 10-year relative risks (RR) for NSTEMI (RR: 1.217), ESRD (RR: 2.624), ILD (RR: 1.377), PAH (RR: 1.625), and all-cause mortality (RR: 1.379) compared to MTX. No statistically significant RR differences were observed for Alzheimer’s dementia, STEMI, or osteoporosis. Conclusion: In this large, real-world observational study, RA patients initiating HCQ had a higher 10-year risk association for ESRD, ILD, PAH, NSTEMI, and all-cause mortality versus MTX initiators. These findings highlight potential differences in systemic risk profiles and are hypothesis generating. However, the results must be interpreted with significant caution due to major limitations, including the potential for residual confounding from unmeasured variables like disease severity and the absence of adherence data. Further prospective research that addresses these limitations is warranted to confirm these associations and explore underlying mechanisms.

Introduction and importance: Rheumatoid arthritis (RA) presents with extra-articular manifestations in 15–25% of cases. Intra-osseous rheumatoid nodules occur in <1% of patients and mimic metastatic disease on imaging. When extra-articular features precede joint symptoms, diagnostic delays are common. Case presentation: A 78-year-old male smoker presented with chronic cough and dyspnea. CT revealed interstitial lung disease and a pulmonary nodule. PET-CT demonstrated multiple FDG-avid osteolytic lesions in ribs, scapula, and spine (SUV 4.2–8.7), suggesting metastatic malignancy. Initial biopsies showed inflammation without malignancy. Four months later, the patient developed polyarthralgia, morning stiffness, and 8-kg weight loss. Hand radiographs revealed erosive arthropathy. Laboratory tests showed rheumatoid factor 240 IU/mL, anti-CCP 185 U/mL, ESR 68 mm/hr, and CRP 42 mg/L. Repeat scapular biopsy identified necrobiotic granulomas consistent with rheumatoid nodules. Clinical discussion: Intra-osseous rheumatoid nodules result from immune complex-mediated tissue necrosis. Inflammatory cytokines activate osteoclasts, creating lytic lesions with high metabolic activity indistinguishable from metastases on PET imaging. Extra-articular manifestations precede joint symptoms in 10–15% of RA cases. Anchoring bias toward malignancy in an elderly smoker with pulmonary nodules and osteolytic lesions delayed alternative diagnoses. Negative initial biopsies and subsequent development of erosive arthropathy prompted diagnostic reconsideration. Conclusion: Extra-articular RA can masquerade as metastatic disease. Intra-osseous rheumatoid nodules represent rare manifestations requiring histological confirmation. Clinicians should consider systemic autoimmune diseases when evaluating unexplained interstitial lung disease with multiple osteolytic lesions, particularly when malignancy screening is negative. Early recognition enables appropriate immunosuppressive therapy and prevents irreversible organ damage.