Search Results (218)

Periprosthetic joint infection (PJI) remains one of the most challenging complications of arthroplasty. Optimal antibiotic strategies and the role of multidisciplinary teams (MDT) are not fully defined. We retrospectively analyzed 86 PJI surgical procedures performed between 2017 and 2023 at a tertiary referral center. Clinical data, microbiology, surgical strategy (debridement, antibiotics, and implant retention -DAIR, one-stage, two-stage) and antibiotic regimens were collected. Outcomes were compared across antibiotic classes and treatment teams: orthopaedics alone, orthopaedics with MDT input, and a dedicated MDT (GRIP). Success was defined as infection-free survival without further surgery. Median patient age was 70 years, with high comorbidity and predominance of Gram-positive, monomicrobial infections. Rifampicin-based regimens were associated with higher cure rates than non-anti-biofilm therapy (OR 4.9, 95% CI 1.4–17.8). Flucloxacillin plus rifampicin achieved outcomes comparable to rifampicin–fluoroquinolone combinations. The strongest predictor of success was MDT involvement: in DAIR procedures, cure reached 100% with MDT versus 48% with orthopaedics alone (p = 0.025). Outcomes were similar between teams in one- and two-stage revisions. In this cohort, rifampicin-based therapy improved outcomes in staphylococcal PJI, and flucloxacillin was a valid alternative partner drug. Crucially, MDT management—particularly in DAIR—was associated with superior results. These findings highlight the value of structured multidisciplinary PJI care pathways alongside optimised antibiotic strategies. Full article

Background: Data on antibiotic treatment for diabetic foot osteomyelitis are limited. This study aims to describe the real-world effectiveness and safety of dalbavancin in treating deep diabetic foot infections. Methods: A retrospective, observational, multicenter study was conducted in nine Spanish hospitals and one Irish hospital. Patients with diabetic foot osteomyelitis treated with dalbavancin were included. Data on demographics, clinical characteristics, microbiology, antibiotic regimens, adverse events, and clinical outcomes were analyzed. Results: Among 136 patients, 76% were male, with a mean age of 69 ± 12 years. Renal insufficiency was observed in 32%, and 6% required renal replacement therapy. Based on the McCabe scale, 70% of patients had a rapidly or ultimately fatal disease. Polypharmacy was noted in 83%, and 60% of infections were moderate. Dalbavancin was primarily used as second-line therapy (92%). The cure rate was 80.9% (95% CI: 73.5–86.6%), achieved after a median of two doses. Patients receiving dalbavancin as first-line therapy had a cure rate of 86%, comparable to 80% in second-line therapy, with no significant differences. Surgical interventions were required in 72% of cases, with minor amputations performed in 40% of patients. Polymicrobial infections were common (55%), and methicillin-resistant Staphylococcus aureus was identified in 26% of cases. Adverse events occurred in 5% of patients. Chronic kidney disease was the sole independent risk factor for therapeutic failure (IRR 0.80, 95% CI: 0.64–1.00, p = 0.045). Conclusions: Dalbavancin is effective and safe for treating diabetic foot osteomyelitis, including in complex patients with resistant microorganisms. Full article

This study advances alkali-activated cementitious materials (AACMs) by developing a ground-granulated blast furnace slag/high-calcium fly ash (GGBS/HCFA) composite that incorporates Tuokexun desert sand and by establishing a clear linkage between activator chemistry, mix proportions, curing regimen, and microstructural mechanisms. The innovation lies in valorizing industrial by-products and desert sand while systematically optimizing the aqueous glass modulus, alkali equivalent, HCFA dosage, and curing temperature/time, and coupling mechanical testing with XRD/FTIR/SEM to reveal performance–structure relationships under thermal and chemical attacks. The optimized binder (aqueous glass modulus 1.2, alkali equivalent 6%, and HCFA 20%) achieved 28-day compressive and flexural strengths of 52.8 MPa and 9.5 MPa, respectively; increasing HCFA beyond 20% reduced compressive strength, while flexural strength peaked at 20%. The preferred curing condition was 70 °C for 12 h. Characterization showed C-(A)-S-H as the dominant gel; elevated temperature led to its decomposition, acid exposure produced abundant CaSO₄, and NaOH exposure formed N-A-S-H, each correlating with strength loss. Quantitatively, acid resistance was weaker than alkali resistance and both deteriorated with concentration: in H₂SO₄, 28-day mass loss rose from 1.22% to 4.16%, with compressive/flexural strength retention dropping to 75.2%, 71.2%, 63.4%, and 57.4% and 65.3%, 61.6%, 58.9%, and 49.5%, respectively; in NaOH (0.2/0.5/0.8/1.0 mol/L), 28-day mass change was +0.74%, +0.88%, −1.85%, and −2.06%, compressive strength declined in all cases (smallest drop 7.77% at 0.2 mol/L), and flexural strength increased at lower alkalinity, consistent with a pore-filling micro-densification effect before gel dissolution/cracking dominates. Practically, the recommended mix and curing window deliver structural-grade performance while improving high-temperature and acid/alkali resistance relative to non-optimized formulations, offering a scalable, lower-carbon route to utilize regional desert sand and industrial wastes in durable cementitious applications. Full article

The focus of treatment of hepatocellular carcinoma (HCC) has shifted significantly from local therapy to systemic drug therapy. Recently, the efficacy of drug therapy for HCC has made rapid progress. We have transitioned from eras of sorafenib monotherapy and sequential therapy with multiple tyrosine kinase inhibitors that slightly improved patient prognoses, to an era where the introduction of immunotherapy combining atezolizumab and bevacizumab has achieved further improvements in patient prognosis. The availability of highly effective drugs has expanded the range of diseases treatable by drug therapy. Additionally, instead of initiating drug therapy at advanced stages, combining it with local therapies such as transarterial chemoembolization at an earlier stage with the aim of achieving a cure has become possible, improving treatment outcomes further. Currently, the number of regimens available for HCC, including combinations of multiple drugs and local therapies, has increased, leading to numerous clinical trials. Additionally, HCC cases that were previously unresectable are now resectable after drug therapy, necessitating the establishment of a resectability classification system. This review summarizes the current evidence for drug therapy for HCC and discusses future treatment strategies, treatment combinations, and prospects. Full article

Background: The official current guideline for Helicobacter pylori (H. pylori) eradication is to use tetracycline–bismuth-based protocols as first line treatment due to the increasing incidence of clarithromycin resistance in the last decade. The unavailability of tetracycline and bismuth-containing medicines, however, is an issue in many countries, limiting the routine use of these protocols. The value of using additional probiotics in eradication protocols is also unclear. Direct comparison data on the effect of available bismuth compounds and different probiotic strains on eradication outcome are limited. Goal: The aim of our investigation was to find optimal eradication protocols, supplementations and treatment duration for routine clinical use in our gastroenterology unit, located in a highly clarithromycin-resistant and tetracycline–bismuth-naïve area. Materials and Methods: We conducted a retrospective real-world data analysis of 402 H. pylori positive patients between 2016 and 2024. H. pylori infection was diagnosed using histological examination of gastroscopy samples obtained from the gastric antrum. For the evaluation of treatment success or failure, ¹⁴C breath tests and stool H. pylori antigen tests were performed. Data on patient characteristics and treatment protocols were collected from our electronic patient record system, and treatment success was compared between the different treatment regimes. Results: Despite the regional clarithromycin resistance, supplementing clarithromycin-based regimens with bismuth and probiotic during the 14-day treatment duration showed a high and comparable cure rate when compared to tetracycline-based regimens, which are the current first-line therapies. When tetracycline-based combination is available, it is recommended to use it with an additional probiotic to achieve the best possible outcome. Comparison of the effect of available bismuth preparations on treatment success showed no significant difference. Generally, probiotic-containing protocols are more successful, compared to those treatments without this supplement. There was no statistical difference in the cure rates amongst the four probiotic strains used, where sample size allowed statistical analysis. Furthermore, supplementation with probiotics Lactobacillus reuteri ATCC PTA 6475 or Lactobacillus reuteri Protectis^® DSM 17938 showed promising high treatment success rates (85.2% and 100.0%, respectively) in our study. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is characterized by chronic relapsing and remitting inflammation of the gastrointestinal tract. Fecal microbiota transplantation (FMT) has emerged as an FDA-approved treatment for recurrent Clostridioides difficile infections (CDIs), with promising potential in patients with IBD. This manuscript aimed to provide a comprehensive and updated review of the available literature on fecal microbiota transplantation, its clinical use in IBD in general, as well as in patients with IBD and CDI. Methods: An extensive literature search was performed from October 2024 to March 2025. All publications available within PubMed, Medline, Embase, Google Scholar, and Cochrane databases were reviewed. All original articles, case reports, review articles, systematic reviews, and meta-analyses were included. Qualitative and quantitative data were both extracted. Discussion: Intestinal microbiota is an integral part of the human body, and dysbiosis (an imbalance in the gut’s microbial community) has been linked with several pathologies. Dysbiosis in IBD is marked by reduced beneficial bacteria and increased pro-inflammatory pathogens, contributing to mucosal damage and immune dysregulation. FMT has emerged as a solution to dysbiosis, with the first case recorded in 1917. FMT has been successful in treating patients with CDI. The diagnostic value of the gut microbiome is currently being explored as a possible therapeutic approach to IBD. Several studies have assessed FMT in patients with IBD and CDI with promising results in both ulcerative colitis (UC) and Crohn’s disease (CD) but varying efficacy based on administration routes, donor selection, and processing methods. In the context of recurrent CDI in patients with IBD, FMT demonstrates a high cure rate and potential benefit in concurrently improving IBD activity. However, risks such as IBD flare-ups post-FMT remain a concern. Conclusions: FMT holds promising potential in the management of CDI in patients with IBD. By restoring microbial diversity and correcting dysbiosis, FMT offers a novel, microbiota-targeted alternative to conventional therapies. While data support its efficacy in improving disease remission, variability in outcomes underscores the need for standardized protocols and additional large-scale, controlled studies. Continued research efforts into donor selection, treatment regimens, and long-term safety will be critical to optimizing FMT’s role in IBD and CDI care as well as improving patient outcomes. Full article

Fanconi anemia (FA) is characterized by faulty DNA repair and is associated with bone marrow failure, acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS). Because of the more widespread use of next-generation sequencing (NGS) and increased testing for germline mutations in young patients with MDS and AML, FA is increasingly being first diagnosed in adults, many of whom lack classical physical stigmata. Hematopoietic stem cell transplant is the only cure for the hematologic manifestations of FA but there are several unique considerations in FA patients, including first maintaining a high index of suspicion for the diagnosis in patients with minimal phenotypic abnormalities, second an exaggerated sensitivity to alkylating agents and radiation, precluding the use of standard myeloablative conditioning regimens despite the young age of most of the patients, and lastly a marked propensity for squamous cell cancers of the upper aerodigestive tract and anogenital region, likely further increased by the drugs used in conditioning and by chronic inflammation in patients who develop graft-versus-host disease. Despite a growing number of FA patients surviving into adulthood or first being diagnosed with FA as an adult, there is minimal literature describing transplant methodology and outcomes. In the following case-based review of a patient, we incorporate recent findings from the literature on the care of this challenging patient population. Full article

Purpose: To assess the impact of beta-lactam therapeutic drug monitoring (TDM) timing and therapy adjustment on clinical cure and 30-day mortality. Methods: This was a prospective study of critically ill patients admitted to the University of Florida Health Shands Hospital intensive care unit (ICU) between 2021 and 2022, ≥18 years old, and requiring beta-lactam therapy for a suspected or confirmed infection. Beta-lactam concentrations were measured per standard of care, pharmacokinetic/dynamic (PK/PD) target attainment was calculated, and therapy was adjusted if needed. Multiple regression and time-to-event (TTE) analyses were performed. Results: A total of 297 infection episodes from 268 patients were included. The mean (SD) age was 56 years (17), weight was 82 kg (32), and 14% received renal replacement therapy. The most common infection source was the lung, and the most common beta-lactam was cefepime. The most common infusion duration was 30 min. The median (IQR) time to first TDM was 2.7 days (1.7–4.7). Fifty-seven percent of patients required therapy adjustment. Increases in beta-lactam dose, frequency, or infusion duration were associated with lower 30-day mortality compared to continuing the same regimen (aOR 0.30, p = 0.015). Delay in performing TDM was associated with lower probability of clinical cure (aOR 0.92, p = 0.0023). Patients who had the regimen increased had shorter hospital stay compared to those who had it decreased. Timing of beta-lactam TDM in ICU patients was a significant predictor of clinical cure, while adjusting beta-lactam therapy to achieve higher exposure was a significant predictor of 30-day mortality. Full article

Background: Acute myeloid leukemia (AML) primarily affects older adults and is associated with poor prognosis, particularly in patients aged ≥ 60 years with comorbidities and adverse disease characteristics. Standard intensive chemotherapy, such as the “7 + 3” regimen, has shown limited efficacy and substantial toxicity in this population, underscoring the need for alternative treatment strategies. In recent years, venetoclax-based regimens have emerged as an important option, demonstrating promising outcomes in elderly patients traditionally considered unfit for intensive therapy and, more recently, even in selected fit patients. Methods: This narrative review provides a comprehensive comparative analysis of intensive chemotherapy and venetoclax-based regimens in elderly AML patients. This review synthesizes evidence from prospective and retrospective clinical trials, with focuses on treatment efficacy, safety, and the ability to bridge patients to curative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: Intensive chemotherapy has achieved complete remission (CR) rates of 40–60% in elderly AML patients, though the median overall survival (OS) rarely exceeds 12 months. Conversely, venetoclax combined with hypomethylating agents has recently demonstrated CR rates of up to 74%, with 83% of responders proceeding to allo-HSCT in selected studies. Venetoclax-based regimens have also been associated with improved tolerability and reduced treatment-related mortality. Discussion: This review highlights a paradigm shift in the management of AML in the elderly. While intensive chemotherapy remains a standard option for selected patients, the increasing use of venetoclax-based regimens represents a novel and effective strategy with the potential to overcome traditional limitations, especially in patients previously deemed ineligible for curative approaches. The high remission and transplantation rates observed with non-intensive therapies support their role not only as a palliative alternative but as a bridge to cure. Conclusions: Venetoclax-based regimens are reshaping the treatment landscape of AML in the elderly, offering high response rates and facilitating access to allo-HSCT. Further research is needed to optimize treatment sequencing, explore novel combinations, and reduce relapse rates after transplants, ultimately improving the long-term outcomes in this high-risk population. Full article

There is still an unmet need for the treatment of high-risk hematological malignancies. To date, allogeneic stem cell transplantation remains the only chance of cure. Most patients suffering from high-risk hematological malignancies are of an older age and often present with comorbidities. Moreover, patients achieving remission often suffer from early relapse. Amongst the different treatment options, sequential conditioning has yet to prove its value against other conditioning regimens. Sequential conditioning relies on a short course of intensive chemotherapy that is quickly followed by immunosuppressive conditioning before allogeneic stem cell transplantation. Here, we will try to determine which patients can benefit from sequential conditioning. Amongst the different sequential regimens, we will also try to assess if one regimen is better than all the others. Despite the several studies conducted on sequential conditioning, very few are prospective work and head-to-head comparisons are almost inexistant. Sequential conditioning also relies on the use of prophylactic donor lymphocyte infusion post-transplantation. Hence, limiting non-relapse complications is of primary importance to the allow administration of post-transplant treatment. In the era of new targeting therapies, is there still a place for sequential conditioning? Can patients benefit from an association of new therapeutic agents and sequential conditioning? Full article

Osteoarthritis (OA) is a chronic and debilitating joint disease characterized by progressive cartilage degeneration for which no definitive cure exists. Conventional management approaches often rely on fragmented and poorly coordinated pharmacological and non-pharmacological interventions that are inconsistently applied throughout the disease course. Persistent controversies regarding the clinical efficacy of chondroprotective agents, frequently highlighted by pharmacovigilance agencies, underscore the need for a structured evidence-based approach. Emerging evidence suggests that synchronizing pharmacotherapy and exercise regimens with circadian biology may optimize therapeutic outcomes by addressing early pathological processes, including low-grade inflammation, oxidative stress, and matrix degradation. Recognizing the influence of the chondrocyte clock on these processes, this study proposes a ‘prototype’ for a novel framework that leverages the circadian rhythm-aligned administration of traditional chondroprotective agents along with tailored, accessible exercise protocols to mitigate cartilage breakdown and support joint function. In addition, this model-based framework emphasizes the interdependence between cartilage chronobiology and time-of-day-dependent responses to exercise, where strategically timed joint activity enhances nutrient and waste exchange, mitigates mitochondrial dysfunction, supports cellular metabolism, and promotes tissue maintenance, whereas nighttime rest promotes cartilage rehydration and repair. This time-sensitive, comprehensive approach aims to slow OA progression, reduce structural damage, and delay invasive procedures, particularly in weight-bearing joints such as the knee and hip. However, significant challenges remain, including inter-individual variability in circadian rhythms, a lack of reliable biomarkers for pharmacotherapeutic monitoring, and limited clinical evidence supporting chronoexercise protocols. Future large-scale, longitudinal trials are critical to evaluate the efficacy and scalability of this rational integrative strategy, paving the way for a new era in OA management. Full article

The prevalence and mortality associated with breast cancer have forced healthcare providers to leverage surgery, chemotherapy, radiation therapy, and immunotherapy to achieve a cure. Whereas mortality has significantly dropped over the decades, long-term toxicities and healthcare costs are prohibitive. Therefore, a better understanding of tumor biology through molecular profiling is being utilized for de-escalation of treatment where appropriate. As research evolves, there is growing evidence that less aggressive treatment regimens, when appropriately tailored, can be equally effective for certain patient populations. This approach not only enhances the quality of life for patients by reducing the financial, physical, and emotional burdens associated with more invasive therapies but also promotes a more personalized treatment strategy. By focusing on precision medicine and understanding the biological characteristics of tumors, healthcare providers and patients can make informed decisions that balance safety with efficacy. The field of molecular profiling is a promising avenue for precision-targeted de-escalation and escalation of therapy to minimize the risk–benefit ratio. Full article

Background: Clindamycin resistance among community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid for treatment of these infections are limited. We sought to reevaluate antibiotic management among invasive CA-MRSA at a tertiary children’s hospital. Methods: Cases of invasive clindamycin-resistant MRSA infections in children were identified through an ongoing S. aureus surveillance study. Eligible cases were those occurring in otherwise healthy children from 2011–2021. Medical records were reviewed. Results: Thirty-four subjects met inclusion criteria. The most common diagnoses were osteomyelitis (n = 17) and deep abscess (n = 7). The median duration of IV therapy was 11.5 days (IQR 6–42 days) and total therapy (IV + oral) was 32 days (IQR 23–42). Overall, 50% of patients were transitioned to oral therapy. Definitive antibiotics used for treatment included vancomycin (n = 15), TMP/SMX (n = 9), linezolid (n = 7), ceftaroline (n = 2), and doxycycline (n = 1). Cure rates were similar across definitive antibiotic therapies (vancomycin-73.3%; TMP/SMX-88.9%; ceftaroline 50%; linezolid and doxycycline-100%). Three subjects died of MRSA disease; two definitively treated with vancomycin and one with ceftaroline. Conclusions: Vancomycin is the most commonly used agent in the treatment of invasive clindamycin-resistant CA-MRSA in children at our center. However, TMP/SMX and linezolid can be considered as oral options when completing treatment in select cases. Further work is needed to evaluate the optimal management of these infections. Full article

Purpose: To evaluate the real-world evidence of ceftazidime-avibactam (CAZ-AVI) compared to intravenous colistin for the treatment of multidrug-resistant (MDR) P. aeruginosa infections. Method: This is a multicenter, retrospective cohort study conducted in the period between 2017 and 2023 at five institutions for patients who received either CAZ-AVI or colistin-based regimens for treating MDR P. aeruginosa infections. Outcomes were compared using multivariate logistic regression analysis. Result: Among the screened patients, 203 patients were included: 89 in the CAZ-AVI group and 114 in the colistin group. A total of 57% presented with pneumonia, 21% with bacteremia, and 61% were in the intensive care unit. The rate of clinical cure was significantly higher among patients who received CAZ-AVI (67% vs. 50%; OR, 2.07; 95% CI, 1.16–3.68). The rate of in-hospital mortality was numerically lower among patients who received CAZ-AVI (40% vs. 49%; OR, 0.58; 95% CI, 0.33–1.03). The rate of AKI was significantly lower among patients who received CAZ-AVI (15% vs. 43%; OR, 0.23; 95% CI, 0.11–0.45). Conclusion: CAZ-AVI was more effective in treating MDR P. aeruginosa infections and showed a better safety profile compared to colistin. Thus, CAZ-AVI could be a better alternative for treating MDR P. aeruginosa infections. Full article

As of 2023, there were 39.9 million people living with Human Immunodeficiency Virus type 1 (HIV-1). Although great strides have been made in treatment options for HIV-1, and our understanding of the HIV-1 life cycle has vastly improved since the start of this global health crisis, a functional cure remains elusive. One of the main barriers to a cure is latency, which allows the virus to persist despite combined antiretroviral therapy (cART). Recently, we have found that exosomes, which are small, membrane-enclosed particles released by virtually all cell types and known to mediate intercellular communication, caused an increase in RNA Polymerase II loading onto the HIV-1 promoter. This resulted in the production of both short- and long-length viral transcripts in infected cells under cART. This current study examines the effects of exosome-associated kinases on bystander cells. The phospho-kinase profiling of exosomes revealed differences in the kinase payload of exosomes derived from uninfected and HIV-1-infected cells, with CDK10, GSK3β, and MAPK8 having the largest concentration differences. These kinases were shown to be biologically active and capable of phosphorylating substrates, and they modulated changes in the cell cycle dynamics of exposed cells. Given the relevance of such effects for the immune response, our results implicate exosome-associated kinases as new possible key contributors to HIV-1 pathogenesis that affect bystander cells. These findings may guide new therapeutic avenues to improve the current antiretroviral treatment regimens. Full article