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British Journal of Cancer Jun 2024Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C;...
BACKGROUND
Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.1); median duration of response (mDOR) 18.0 months (95% CI: 12.4, 46.4). We report outcomes in Asian patients from VISION (Cohort A + C) (cut-off: November 20, 2022).
METHODS
Patients with advanced METex14 skipping NSCLC, detected by liquid or tissue biopsy, received tepotinib 500 mg (450 mg active moiety) once daily.
PRIMARY ENDPOINT
objective response (RECIST 1.1) by independent review. Secondary endpoints included: DOR, progression-free survival (PFS), overall survival (OS), safety, and health-related quality of life (HRQoL).
RESULTS
Across treatment lines in 106 Asian patients (39.6% female, 43.4% smoking history, 79.2% adenocarcinoma, 47.2% treatment-naive), ORR was 56.6% (95% CI: 46.6, 66.2), mDOR 18.5 months (10.4, ne), mPFS 13.8 months (10.8, 22.0), and mOS 25.5 months (19.3, 36.4). Consistent efficacy observed, regardless of baseline characteristics. HRQoL remained stable during treatment. Treatment-related adverse events (TRAEs) occurred in 95.3% of patients (39.6% Grade ≥3). Most common TRAEs: peripheral edema (62.3%), creatinine increase (38.7%).
CONCLUSIONS
Tepotinib demonstrated robust and durable efficacy, with a manageable safety profile, in Asian patients with METex14 skipping NSCLC.
CLINICAL TRIAL REGISTRATION
NCT02864992.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Female; Male; Middle Aged; Lung Neoplasms; Aged; Proto-Oncogene Proteins c-met; Adult; Exons; Quality of Life; Aged, 80 and over; Asian People; Pyrimidines; Progression-Free Survival; Piperidines; Pyridazines
PubMed: 38575731
DOI: 10.1038/s41416-024-02615-9 -
Medicine Mar 2024Puerperal sepsis is a life-threatening condition caused by infection that can rapidly progress to multisystem infection and toxin-mediated shock. Symmetrical peripheral...
RATIONALE
Puerperal sepsis is a life-threatening condition caused by infection that can rapidly progress to multisystem infection and toxin-mediated shock. Symmetrical peripheral gangrene is defined as symmetrical distal ischemic damage in two or more sites in the absence of major vascular occlusive disease. The syndrome is devastating and rare. In this study, we introduce a case of puerperal septicemia complicated by symmetrical peripheral gangrene.
PATIENT CONCERNS
A 23-year-old woman delivered a live female infant vaginally after cervical balloon dilatation at 39 weeks of gestation. Persistent hyperthermia developed on the first postpartum day. After experiencing ventricular fibrillation, acute liver failure, and acute pulmonary edema, she developed blackened extremities on the 5th postpartum day.
DIAGNOSES
Puerperal septicemia complicated by symmetrical peripheral gangrene.
INTERVENTIONS
Upon transfer to our hospital, the patient was enrolled in the intensive care unit and underwent anti-infective and amputation surgery.
OUTCOMES
After the surgery, the patient recovered well and was successfully discharged from the hospital.
LESSONS
Early detection and timely treatment is the best way to reduce the mortality and sequelae of puerperal sepsis. Physicians should be alert to the possibility of comorbid symmetrical peripheral gangrene when sepsis patients present with hepatic impairment.
Topics: Humans; Female; Young Adult; Adult; Gangrene; Shock, Septic; Extremities; Amputation, Surgical; Postpartum Period
PubMed: 38552074
DOI: 10.1097/MD.0000000000037571 -
Frontiers in Cellular Neuroscience 2024Ischemic stroke is a major disease causing death and disability in the elderly and is one of the major diseases that seriously threaten human health and cause a great... (Review)
Review
Ischemic stroke is a major disease causing death and disability in the elderly and is one of the major diseases that seriously threaten human health and cause a great economic burden. In the early stage of ischemic stroke, neuronal structure is destroyed, resulting in death or damage, and the release of a variety of damage-associated pattern molecules induces an increase in neuroglial activation, peripheral immune response, and secretion of inflammatory mediators, which further exacerbates the damage to the blood-brain barrier, exacerbates cerebral edema, and microcirculatory impairment, triggering secondary brain injuries. After the acute phase of stroke, various immune cells initiate a protective effect, which is released step by step and contributes to the repair of neuronal cells through phenotypic changes. In addition, ischemic stroke induces Central Nervous System (CNS) immunosuppression, and the interaction between the two influences the outcome of stroke. Therefore, modulating the immune response of the CNS to reduce the inflammatory response and immune damage during stroke is important for the protection of brain function and long-term recovery after stroke, and modulating the immune function of the CNS is expected to be a novel therapeutic strategy. However, there are fewer studies on B-cells in brain function protection, which may play a dual role in the stroke process, and the understanding of this cell is still incomplete. We review the existing studies on the mechanisms of the role of B-cells, inflammatory response, and immune response in the development of ischemic stroke and provide a reference for the development of adjuvant therapeutic drugs for ischemic stroke targeting inflammatory injury.
PubMed: 38550918
DOI: 10.3389/fncel.2024.1340756 -
Cureus Feb 2024Persistent sciatic artery (PSA) is an exceptionally rare congenital vascular anomaly with profound clinical implications. This condition occurs when the primitive...
Persistent sciatic artery (PSA) is an exceptionally rare congenital vascular anomaly with profound clinical implications. This condition occurs when the primitive sciatic artery, responsible for fetal lower limb blood supply, fails to regress during embryonic development. PSA persists into adulthood, representing an intriguing vascular variation that can present as gluteal aneurism and thrombosis. We present the case of a 72-year-old female patient admitted with abdominal pain and blackening of her right foot. Clinical examination revealed dry gangrene affecting the toes, limb edema, and absent peripheral pulses in the right lower limb. Septic shock and electrolyte imbalances prompted immediate resuscitation and antibiotic therapy. Diagnostic investigations, including Doppler ultrasonography, CT angiography, and 2D echocardiography, identified a right-sided PSA. With limb ischemia being irreversible, a below-knee amputation was performed. This case highlights the clinical presentation, diagnostic workup, and management of a rare PSA, emphasizing the importance of prompt recognition and intervention in complex vascular anomalies.
PubMed: 38550468
DOI: 10.7759/cureus.55023 -
La Tunisie Medicale Jan 2024Anti-tumor necrosis factor α (anti-TNF α) agents are an effective treatment for a variety of inflammatory and autoimmune diseases. In ophthalmology anti-TNF α began... (Review)
Review
INTRODUCTION
Anti-tumor necrosis factor α (anti-TNF α) agents are an effective treatment for a variety of inflammatory and autoimmune diseases. In ophthalmology anti-TNF α began to emerge as a possible therapy for non-infectious uveitis, paradoxically their administration may result in the onset or recurrence of inflammatory eye disease such as uveitis. We reported a case of new onset of bilateral anterior and intermediate uveitis in a patient with rheumatoid arthritis (RA) while being treated with infliximab and we performed a review of literature.
OBSERVATION
A 25-year-old female with RA under infliximab, presented with bilateral blurred vision. Anterior segment examination demonstrated retrodescmetic fine precipates, 1+ cells in the anterior chamber on both eyes. The fundus examination was difficult because of the vitritis. Fluorescein angiography demonstrated mild optic disc edema, and bilateral diffuse peripheral fern leaf cappilaritis. Optical coherence tomography showed severe cystoid macular edema bilaterally. The diagnosis of bilateral anterior and intermediate uveitis caused by infliximab was retained after exclusion of infectious and autoimmune aetiologies. She was treated with corticosteroid with good visual outcome.
CONCLUSION
In our case, new onset of uveitis may be considered as paradoxical effect of anti-TNF α therapy. Rheumatologists and ophthalmologists should be aware of this effect. Careful monitoring of patients under infliximab is necessary for appropriate diagnosis and early treatment.
Topics: Female; Humans; Adult; Infliximab; Tumor Necrosis Factor Inhibitors; Uveitis; Tumor Necrosis Factor-alpha; Uveitis, Intermediate; Arthritis, Rheumatoid
PubMed: 38545732
DOI: 10.62438/tunismed.v102i1.4564 -
Journal of Clinical Medicine Mar 2024(1) : Type 2 diabetes is a major cause of incidences and the progression of peripheral artery disease (PAD). Bone marrow edema (BME) is an important finding suggestive...
(1) : Type 2 diabetes is a major cause of incidences and the progression of peripheral artery disease (PAD). Bone marrow edema (BME) is an important finding suggestive of underlying bone inflammation in non-traumatic diabetic patients with PAD. Our aim was to evaluate the presence, severity, and clinical implications of BME detected by virtual non-calcium application (VNCa) of dual-energy CT angiography (DE-CTA). (2) : A consecutive series of 76 diabetic patients (55 men; mean age 71.6 ± 11.2 yrs) submitted to lower limb DE-CTA for PAD evaluation and revascularization planning, which were retrospectively analyzed. VNCa images were independently and blindly revised for the presence, location, and severity of BME by two radiologists with 10 years of experience. BME and non-BME groups were evaluated in terms of PAD clinical severity and 6-month secondary major amputation rate. (3) : BME was present in 17 (22%) cases, while 59 (78%) patients were non-BME. The BME group showed a significantly higher incidence of major amputation ( < 0.001) and a significantly higher number of patients with advanced clinical stages of PAD compared to the non-BME group ( = 0.024). (4) : Lower limb DE-CTA with VNCa application is a useful tool in the detection of BME in diabetic patients with PAD, simultaneously enabling the evaluation of the severity and location of the arterial disease for revascularization planning. BME presence could be a marker of clinically severe PAD and a possible risk factor for revascularization failure.
PubMed: 38541762
DOI: 10.3390/jcm13061536 -
Life (Basel, Switzerland) Mar 2024In traditional Korean medicines, is commonly included for the remedy of atopic dermatitis, and magnolol is a major constituent of . Its pharmacological effects include...
In traditional Korean medicines, is commonly included for the remedy of atopic dermatitis, and magnolol is a major constituent of . Its pharmacological effects include anti-inflammatory, hepatoprotective, and antioxidant effects. Using BALB/c mice repeatedly exposed to 1-chloro-2,4-dinitrobenzene (DNCB), magnolol was evaluated in atopic dermatitis-like lesions. Administration of magnolol (10 mg/kg, intraperitoneal injection) markedly relieved the skin lesion severity including cracking, edema, erythema, and excoriation, and significantly inhibited the increase in IgE levels in the peripheral blood. A DNCB-induced increase in mast cell accumulation in atopic dermatitis skin lesions was reversed by magnolol administration, as well as a rise in expression levels of pro-inflammatory Th2/Th17/Th1 cytokines' (IL-4, IL-13, IL-17A, IFN-γ, IL-12A, TARC, IL-8, and IL-6) mRNAs in the lymph nodes and skin (n = 5 per group). In lymph nodes, magnolol reversed DNCB's increase in CD4RORγt Th17 cell fraction and decrease in CD4FoxP3 regulatory T cell fraction. The results also showed that magnolol suppressed T cell differentiation into Th17 and Th2 cells, but not Th1 cells. Magnolol suppresses atopic dermatitis-like responses in the lymph nodes and skin, suggesting that it may be feasible to use it as a treatment for atopic dermatitis through its suppression of Th2/Th17 differentiation.
PubMed: 38541664
DOI: 10.3390/life14030339 -
Journal of Personalized Medicine Feb 2024Peripheral artery disease is a condition that causes narrowing of the arteries, impairing circulation to the extremities. Globally, it affects millions of people and is...
Peripheral Arterial Disease in the Context of Acute Coronary Syndrome: A Comprehensive Analysis of Its Influence on Ejection Fraction Deterioration and the Onset of Acute Heart Failure.
BACKGROUND
Peripheral artery disease is a condition that causes narrowing of the arteries, impairing circulation to the extremities. Globally, it affects millions of people and is more prevalent in older adults and those with diabetes, high blood pressure, or high cholesterol. There is an overlap specific to polyvascular patients, and almost 50% of patients with PAD have coronary artery disease. Compelling evidence reveals a noteworthy association between PAD and major adverse cardiovascular events (MACEs) in individuals experiencing acute coronary syndrome (ACS) but limited knowledge exists regarding the influence of PAD on left ventricular systolic function during ACS.
METHODS
In a retrospective case-control study, we examined 100 participants who presented with ACS (mean age = 61.03 years, 80 [80%] males). The patients were divided into two groups: the ACS-PAD group (32 subjects, 74% of them with STEMI, 10% with NSTEMI, and 16% with NSTEACS) and the ACS-nonPAD group (68 participants).
RESULTS
This study highlighted that PAD negatively impacts patients with non-ST-segment elevation myocardial infarction (NSTEMI). These patients were likely to experience a decline of approximately 19.3% in their left ventricular ejection fraction (LVEF) compared to the ACS-nonPAD group ( = 0.003) and presented a worse clinical status (the PAD group correlated with Killip class IV, = 0.049).
CONCLUSION
Our analysis indicates that patients diagnosed with NSTEACS and PAD tend to have a higher LVEF of over 55% and a lower HEART score. Patients with PAD tend to have a functionally higher EF but clinically present with more unstable scenarios (pulmonary edema and cardiogenic shock). This is mainly driven by a higher prevalence of HFpEF in the PAD group. Looking closer at the PAD group, they have a higher incidence of comorbidities such as diabetes, hypertension, high cholesterol, CAD, and stroke, as well as being more active smokers.
PubMed: 38540993
DOI: 10.3390/jpm14030251 -
Therapeutic Advances in Neurological... 2024Magnetic resonance imaging of peripheral nerves in the wrist and palm is challenging due to the small size, tortuous course, complex surrounding tissues, and...
BACKGROUND
Magnetic resonance imaging of peripheral nerves in the wrist and palm is challenging due to the small size, tortuous course, complex surrounding tissues, and accompanying blood vessels. The occurrence of carpal palmar lesions leads to edema, swelling, and mass effect, which may further interfere with the display and identification of nerves.
OBJECTIVE
To evaluate whether contrast-enhanced magnetic resonance neurography (ceMRN) improves the visualization of the morphology and pathology of the median, ulnar nerves, and their small branches in the wrist and palm.
DESIGN
An observational study.
METHODS
In total 57 subjects, including 36 volunteers and 21 patients with carpal palmar lesions, were enrolled and underwent ceMRN and non-contrast MRN (ncMRN) examination at 3.0 Tesla. The degree of vascular suppression, nerve visualization, diagnostic confidence, and lesion conspicuity was qualitatively assessed by two radiologists. Kappa statistics were obtained for inter-reader agreement. The signal-to-noise ratio, contrast ratio (CR), and contrast-to-noise ratio (CNR) of the median nerve were measured. The subjective ratings and quantitative measurements were compared between ncMRN and ceMRN.
RESULTS
The inter-reader agreement was excellent ( > 0.8) for all qualitative assessments and visualization assessment of each nerve segment. Compared with ncMRN, ceMRN significantly improved vascular suppression in volunteers and patients (both < 0.001). The ceMRN significantly enhanced nerve visualization of each segment (all < 0.05) and diagnostic confidence in volunteers and patients (both < 0.05). The ceMRN improved lesion conspicuity ( = 0.003) in patients. Quantitatively, ceMRN had significantly higher CRs of nerve subcutaneous fat, bone marrow, and vessels and CNR of nerve vessel than ncMRN (all < 0.05).
CONCLUSION
The ceMRN significantly improves the visualization of peripheral nerves and pathology in the wrist and palm by robustly suppressing the signals of fat, bone marrow, and especially vessels in volunteers and patients.
PubMed: 38532801
DOI: 10.1177/17562864241239739