Search Results (2,710)

Aseptic abscess syndrome is a clinical entity that is being increasingly documented. Unfortunately, apart from the French registry, there are no other studies presenting collective data. In this review, we sought to analyze clinical and laboratory data from case reports published from the rest of the world. A total of 107 articles were found through our literature search in PubMed, Scopus, and Google, which contained 108 patients who met our eligibility criteria, including pediatric cases. The mean age at diagnosis was 39.1 years, and 54.6% of the patients were female. Cases were found affecting almost every organ, but the most common abscess locations were the spleen (51.9%), liver (35.2%), and lung (23.1%); 34.3% of the patients had multiorgan disease at diagnosis. An inflammatory syndrome was evident, with fever (79.6%), pain (66.7%), median white blood cell count of 16,200/μL, median C-reactive protein level of 15.5 mg/dL, and mean erythrocyte sedimentation rate of 79 mm/h. In total, 88.9% had an associated disease, with the most frequent being neutrophilic dermatosis (43.5%) and inflammatory bowel disease (31.5%); associated disease was inactive during abscess diagnosis in approximately one-quarter of patients. Moreover, 93.5% received corticosteroids with or without other agents, while 21.3% underwent excision surgery, which led to relapse if immunosuppressants were not concomitantly administered. No deaths were reported due to the syndrome, but 42.4% of cases that provided relevant data relapsed despite the relatively short follow-up period (median 1 year), either in the same or different organs. Combined immunomodulatory treatment, based on subgroup analysis, appeared protective against relapse in females and patients with splenic abscess or C-reactive protein >12 mg/dL (odds ratio 0.16 [95% CI 0.04–0.59]/p = 0.004, 0.09 [95% CI 0.01–0.62]/p = 0.008 and 0.23 [95% CI 0.06–0.92]/p = 0.03, respectively). Infection should always be the working diagnosis in patients with abscesses. However, if the infectious workup is negative, antimicrobials have failed, and no sepsis is present, then aseptic abscess syndrome should be considered; response to high-dose corticosteroids is a therapeutic criterion in almost all cases. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article

Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) alleviate stress on multiple organs. SGLT2i has been demonstrated to benefit heart failure, hemodynamic regulation, and renal protection while GLP-1RA on the other hand has been shown to demonstrate a strong impact on glycemic management, weight loss, and atherosclerotic cardiovascular disease. This review will aim to understand and evaluate the mechanistic rationalization, clinical evidence, and the potential therapeutic treatment of SGLT2 inhibitors and GLP-1 receptor agonists to treat individuals who have CKM syndrome. This analysis also assesses whether combination therapy can be a synergistic approach that may benefit patients but is still underutilized because of the lack of clear guidelines, the associated costs, and disparities in accessibility. Therefore, in this review, we will be discussing the combination therapy’s additive and synergistic effects, current recommendations and clinical evidence, and mechanistic insights of these GLT2 inhibitors and GLP-1 receptor agonists in CKM syndrome patients. Overall, early and combination usage of GLP-1RA and SGLT2i may be essential to demonstrating a significant shift in modern cardiometabolic therapy toward patient-centered care. Full article

With increasing life expectancy, the number of older people living with comorbid diabetes and frailty is increasing. The development of frailty accelerates diabetes-related adverse outcomes. Frailty is a multidimensional syndrome with physical, mental and social aspects which is associated with increased risk of hypoglycaemia, dementia and hospitalisation. Therefore, regular screening for all aspects of frailty should be an integrated part of the care plans of older people with diabetes. In addition, every effort should be made for prevention, which includes adequate nutrition combined with regular resistance exercise training. In already frail older people with diabetes, metabolic targets should be relaxed and hypoglycaemic agents should be of low hypoglycaemic risk potential. Furthermore, the metabolic phenotype of frailty should be considered when choosing hypoglycaemic agents and determining targets. With increasing severity of frailty, proactive chronological plans of de-escalation, palliation and end-of-life care should be considered. These plans should be undertaken in a shared decision-making manner which involves patients and their families. This ensures that patients’ views, wishes and preferences are in the heart of these plans. Full article

T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin’s lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring. Full article

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article

Identity-based cryptography introduced by Shamir (Crypto’84) has seen many advances through the years. In the context of post-quantum identity-based schemes, most of the efficient designs are based on lattices. In this work, we propose an identity-based identification (IBI) scheme and an identity-based signature (IBS) scheme based on codes. Our design combines the hash-and-sign signature scheme, Wave, with a Stern-like signature scheme, BGKM-SIG1, instantiated over a ternary field using the large-weight Syndrome Decoding Problem (SDP). Our scheme significantly outperforms existing code-based identity-based signature constructions. Full article

Insulin resistance (IR) plays a pivotal role in the pathogenesis of several dermatological diseases, including psoriasis, acne, acanthosis nigricans, and hidradenitis suppurativa (HS). These conditions are characterized by chronic inflammation, oxidative stress, and metabolic dysfunction, which are exacerbated by IR. This narrative review examines the emerging role of nutraceutical insulin-sensitizing agents (ISAs), including myo-inositol, alpha-lipoic acid, vitamin D, vitamin C, and folic acid, in managing IR-related dermatological disorders. A comprehensive literature search was conducted across Cochrane Library and MEDLINE (1965–May 2025), focusing on clinical trials involving nutraceutical ISAs in dermatological conditions associated with IR. Only human studies published in English were included. Evidence from randomized controlled trials (RCTs) and observational studies suggests that ISAs improve glycemic control, reduce oxidative stress, and modulate inflammatory pathways in IR-related dermatoses. Notably, myo-inositol combined with magnesium and folic acid has demonstrated significant reductions in acne severity, hirsutism, and quality-of-life impairments in women with polycystic ovary syndrome. Similar benefits have been observed in psoriasis and HS, though data remain limited. Nutraceutical ISAs offer a promising adjunctive approach for the management of IR-associated dermatological diseases, potentially addressing both metabolic dysfunction and skin inflammation. However, robust RCTs with long-term follow-up are needed to confirm these preliminary findings and to establish optimal treatment regimens. Full article

Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due to multi-morbidity, polypharmacy, and age-related physiological changes. Given advancements in medicine and more prolonged cumulative exposure to risk factors in the elderly population, it is likely that the prevalence of chronic kidney disease (CKD) and heart failure (HF) will continue to rise going forward. Hence, understanding the mechanisms involved in the development of CRS is paramount. There are five different CRS types—they are categorised depending on the primary organ involved the acuity of disease. The pathophysiological process behind CRS is complex, involving the interplay of many processes including hemodynamic changes, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction and vascular stiffness. The numerous diagnostic and management challenges associated with CRS are significantly further exacerbated in an elderly population. Biomarkers used to aid the diagnosis of CRS, such as serum creatinine and brain natriuretic peptide (BNP), can be challenging to interpret in the elderly population due to age-related renal senescence and multiple comorbidities. Polypharmacy can contribute to the development of CRS and therefore, before initiating treatment, coordinating a patient-centred, multi-speciality, holistic review to assess potential risks versus benefits of prescribed treatments is crucial. The overall prognosis of CRS in the elderly remains poor. Treatments are primarily directed at addressing the sequelae of the underlying aetiology, which often involves the removal of fluid through diuretics or ultrafiltration. Careful considerations when managing elderly patients with CRS is essential due to the high prevalence of frailty and functional decline. As such, in these patients, early discussions around advance care planning should be prioritised. Full article

Background: Midportion Achilles tendinopathy (Mid-AT) is a complex condition that may be exacerbated by anatomical variations of the plantaris tendon. Recent anatomical studies, particularly the classification proposed by Olewnik et al., have enhanced the understanding of plantaris–Achilles interactions and their clinical implications. Objective: This review aims to assess the anatomical types of the plantaris tendon, their imaging correlates, and the impact of the Olewnik classification on diagnosis, treatment planning, and surgical outcomes in patients with Mid-AT. Methods: We present an evidence-based analysis of the six anatomical types of the plantaris tendon and their relevance to Achilles tendinopathy, with emphasis on MRI and ultrasound (USG) evaluation. A diagnostic and therapeutic algorithm is proposed, and clinical outcomes of both conservative and operative management are compared across tendon types. Results: Types I and V were most strongly associated with symptomatic conflict and showed the highest benefit from surgical resection. Endoscopic approaches were effective in Types II and III, while Type IV typically responded to conservative treatment. Type VI, often misdiagnosed as tarsal tunnel syndrome, required combined neurolysis. The classification significantly improves surgical decision-making, reduces overtreatment, and enhances diagnostic precision. Conclusions: The Olewnik classification provides a reproducible, clinically relevant framework for individualized management of Mid-AT. Its integration into imaging protocols and treatment algorithms may improve therapeutic outcomes and guide future research in orthopaedic tendon pathology. Full article

We consider the problem of privately updating a message out of K messages from N replicated and non-colluding databases where a user has an outdated version of the message ${\hat{W}}_{\theta }$ of length L bits that differ from the current version $W_{\theta }$ in at most f bits. The user also has a cache containing coded combinations of the K messages (with a pre-specified structure), which are unknown to the N databases (unknown prefetching). The cache Z contains ℓ linear combinations from all K messages in the databases with $r=\frac{\mathcal{l}}{L}$ being the caching ratio. The user needs to retrieve $W_{\theta }$ correctly using a private information retrieval (PIR) scheme without leaking information about the message index $\theta$ to any individual database. Our objective is to jointly design the prefetching (i.e., the structure of said linear combinations) and the PIR strategies to achieve the least download cost. We propose a novel achievable scheme based on syndrome decoding where the cached linear combinations in Z are designed to be bits pertaining to the syndrome of $W_{\theta }$ according to a specific linear block code. We derive a general lower bound on the optimal download cost for $0\le r\le 1$, in addition to achievable upper bounds. The upper and lower bounds match for the cases when r is exceptionally low or high, or when $K=3$ messages for arbitrary r. Such bounds are derived by developing novel cache-aided arbitrary message length PIR schemes. Our results show a significant reduction in the download cost if $f<{\displaystyle \frac{L}{2}}$ when compared with downloading $W_{\theta }$ directly using typical cached-aided PIR approaches. Full article

Elevated levels of atherogenic lipoproteins are known to be associated with an increased risk of incident and recurrent cardiovascular events. Knowing that the immediate post-acute coronary syndrome (ACS) period is associated with the maximum risk of recurrent events, the gradual escalation of therapy allows the patient to remain above the targets during the most vulnerable period. In addition, the percentage of lipid-lowering levels for each class of drugs is predictable and has a ceiling. Hence, it is prudent to immediately start with a combination of lipid-lowering drugs following ACS according to the baseline lipid levels. Multiple studies with injectable lipid-lowering agents (PCSK9 inhibitors) such as EVOPACS, PACMAN MI, and HUYGENS MI have shown the feasibility of achieving LDL-C goals by day 28 and beneficial plaque modification in non-infarct-related coronary arteries. Recently, a study from India demonstrated that an upfront triple combination of oral lipid-lowering agents was able to achieve LDL-C goals in a majority of patients in the early post-ACS period. This notion is also supported by a few recent lipid-lowering guidelines advocating for an upfront dual combination of a high-intensity statin and ezetimibe following ACS. Henceforth, the goal should not only be the achievement of lipid targets but also their early achievement. However, the impact of this strategy on long-term cardiovascular outcomes is yet to be ascertained. Full article

Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum IVF Clinic in Athens, Greece, the study included 250 women aged 25–45 who underwent IVF for embryo banking. The protocol involved administering 150 mg of CC daily from day 2 of the menstrual cycle until the day before hCG trigger, alongside 150 IU/day of Meriofert. Outcomes assessed included oocyte yield, fertilization rates, incidence of ovarian hyperstimulation syndrome (OHSS), and hormonal correlations. Comparative and regression analyses explored differences between age groups and predictors of success. Results: The protocol demonstrated a favorable safety profile with no cases of OHSS and yielded a mean of 10.25 oocytes per patient. Group analysis showed significantly more oocytes retrieved in women under 40 (mean: 12.5) versus those over 40 (mean: 8.43), while fertilization rates were paradoxically higher in the older cohort (59.16% vs. 30.68%, p < 0.0001). Regression models revealed basal FSH to be a significant inverse predictor of oocyte yield, but it was positively associated with fertilization rate. Continuous CC use effectively suppressed premature LH surges without compromising oocyte or embryo quality, allowing flexible and cost-effective stimulation with minimal monitoring. Conclusions: Continuous administration of clomiphene citrate in combination with gonadotropins presents a promising, antagonist-free ovarian stimulation protocol for embryo banking. The approach is economically efficient, reduces monitoring requirements, and maintains safety and effectiveness and is particularly notable in women over 40. Further studies are warranted to validate these findings and refine protocol mechanisms. Full article

Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce protein misfolding, and promote chronic neuroinflammation, creating a positive feedback loop of neuronal damage and cognitive decline. Despite its centrality in promoting disease progression, attempts to neutralize oxidative stress with monotherapeutic antioxidants have largely failed owing to the multifactorial redox imbalance affecting each patient and their corresponding variation. We are now at the threshold of precision redox medicine, driven by advances in syndromic multi-omics integration, Artificial Intelligence biomarker identification, and the precision of patient-specific therapeutic interventions. This paper will aim to reveal a mechanistically deep assessment of oxidative stress and its contribution to diseases of neurodegeneration, with an emphasis on oxidatively modified proteins (e.g., carbonylated tau, nitrated α-synuclein), lipid peroxidation biomarkers (F2-isoprostanes, 4-HNE), and DNA damage (8-OHdG) as significant biomarkers of disease progression. We will critically examine the majority of clinical trial studies investigating mitochondria-targeted antioxidants (e.g., MitoQ, SS-31), Nrf2 activators (e.g., dimethyl fumarate, sulforaphane), and epigenetic reprogramming schemes aiming to re-establish antioxidant defenses and repair redox damage at the molecular level of biology. Emerging solutions that involve nanoparticles (e.g., antioxidant delivery systems) and CRISPR (e.g., correction of mutations in SOD1 and GPx1) have the potential to transform therapeutic approaches to treatment for these diseases by cutting the time required to realize meaningful impacts and meaningful treatment. This paper will argue that with the connection between molecular biology and progress in clinical hyperbole, dynamic multi-targeted interventions will define the treatment of neurodegenerative diseases in the transition from disease amelioration to disease modification or perhaps reversal. With these innovations at our doorstep, the future offers remarkable possibilities in translating network-based biomarker discovery, AI-powered patient stratification, and adaptive combination therapies into individualized/long-lasting neuroprotection. The question is no longer if we will neutralize oxidative stress; it is how likely we will achieve success in the new frontier of neurodegenerative disease therapies. Full article