Search Results (3,144)

The emergence and spread of HIV drug resistance mutations (DRMs) pose a threat to current and future treatment options. To inform policy, this review aimed to determine the magnitude and patterns of DRMs in patients on ART in Tanzania. A systematic literature search was conducted in MEDLINE through PubMed, Embase, and CINAHL up to December 2024. A total of 9685 HIV patients from 23 eligible studies were analyzed. The prevalence of virological failure in studies that used a threshold of >1000 and >400 copies/mL was 24.83% (95% CI: 17.85–32.53%) and 36.94% (95% CI: 24.79–50.00%), respectively. Major DRMs were observed at 87.61% (95% CI: 76.25–95.91%). A decrease in prevalence was observed in studies conducted from 2019, with a pooled prevalence of 62.15% (95% CI: 31.57–88.33%). The most frequently observed HIV-1 subtypes were subtype C at 36.20% (95% CI: 30.71–41.85%), A1 at 33.13% (95% CI: 28.23–38.20%), and subtype D at 16.00% (95% CI: 11.41–21.12%), while recombinant forms of the virus were observed at 13.29% (95% CI: 9.79–17.17%). The prevalence of DRMs against NRTIs and NNRTIs was significantly high, while that against INSTIs and PIs was low, supporting the continued use of PI- and INSTI-based regimens in Tanzania and the need for continued surveillance of DRMs. Full article

Workplace violence (WV) is a ubiquitous risk in healthcare settings where it has been associated with physical and mental health problems. We aimed to investigate the relationship between the violence experienced by healthcare workers (HCWs) and the presence of eating disorders (EDs). During routine health surveillance, 1215 HCWs were questioned about their experience of WV and the short version of the Eating Disorder Examination Questionnaire (EDE-QS) was used to assess their eating behaviors. Sleep quality, stress, and the presence of common mental illnesses and metabolic disorders were also evaluated. HCWs who had experienced one or more assaults in the previous year had a significantly higher EDE score than their colleagues. In a multivariate model, WV doubled the risk of EDs (odds ratio 2.33, confidence intervals 95% 1.30; 4.18, p < 0.01). A very significant association was observed between common mental disorders and EDs (OR 1.13, CI 95% 1.04; 1.23, p < 0.01), while low sleep quality almost reached a significant level (OR 1.09, CI 95% 0.99; 1.20). The higher frequency of EDs among workers subjected to violence may result from maladaptive coping mechanisms used when stress and mental health problems caused by WV lead to compensatory overeating. However, reverse causation, where WV is induced by stigmatization, cannot be ruled out. Because of the considerable impact EDs have on physical and mental health, productivity, and patient care, healthcare organizations should adopt programs designed to prevent these disorders in HCWs. Full article

The perianal skin is a unique “skin–gut” boundary that serves as a critical hotspot for the exchange and evolution of antibiotic resistance genes (ARGs). However, its role in the dissemination of antimicrobial resistance (AMR) has often been underestimated. To characterize the resistance patterns in the perianal skin environment of patients with perianal diseases and to investigate the drivers of AMR in this niche, a total of 51 bacterial isolates were selected from a historical strain bank containing isolates originally collected from patients with perianal diseases. All the isolates originated from the skin site and were subjected to antimicrobial susceptibility testing, whole-genome sequencing, and co-occurrence network analysis. The analysis revealed a highly structured resistance pattern, dominated by two distinct modules: one representing a classic Staphylococcal resistance platform centered around mecA and the bla operon, and a broad-spectrum multidrug resistance module in Gram-negative bacteria centered around tet(A) and predominantly carried by IncFIB and other IncF family plasmids. Further analysis pinpointed IncFIB-type plasmids as potent vehicles driving the efficient dissemination of the latter resistance module. Moreover, numerous unexplained resistance phenotypes were observed in a subset of isolates, indicating the potential presence of emerging and uncharacterized AMR threats. These findings establish the perianal skin as a complex reservoir of multidrug resistance genes and a hub for mobile genetic element exchange, highlighting the necessity of enhanced surveillance and targeted interventions in this clinically important ecological niche. Full article

Background: Immune checkpoint inhibitor therapy in patients with lung cancer and metastatic melanoma is associated with exacerbation of autoimmune-related diseases. The efficacy of treatment targeting the programmed cell death receptor-1 (PD-1) checkpoint relies upon a feedback loop between interferon gamma (IFN-γ) and the interleukin-12 isoform, IL-12p40. Paradoxically, both cytokines and the anti-PD-1 antibody worsen psoriasis. We previously reported an immunomodulating peptide, designated IK14004, that inhibits progression of Lewis lung cancer in mice yet uncouples IFN-γ from IL-12p40 production in human immune cells. Methods: Immune cells obtained from healthy donors were exposed to IK14004 in vitro to further characterise the signalling pathways affected by this peptide. Using C57BL/6 immunocompetent mice, the effect of IK14004 was tested in models of lung melanoma and psoriatic skin. Results: Differential effects of IK14004 on the expression of IFN-α/β, the interleukin-15 (IL-15) receptor and signal transducers and activators of transcription were consistent with immune responses relevant to both cancer surveillance and immune tolerance. Moreover, both melanoma and psoriasis were inhibited by the peptide. Conclusions: Taken together, these findings suggest mechanisms underlying immune homeostasis that could be exploited in the setting of cancer and autoimmune pathologies. Peptide administered together with checkpoint blockers in relevant models of autoimmunity and cancer may offer an opportunity to gain further insight into how immune tolerance can be retained in patients receiving cancer immunotherapy. Full article

Background/Objectives: The two major subtypes of inflammatory bowel disease (IBD)—Crohn’s disease (CD) and ulcerative colitis (UC)—are known to increase the likelihood of developing colorectal cancer (CRC). While this relationship has been well studied in Western populations, evidence from East Asia remains limited and inconsistent. Using nationwide cohort data, this study explored the potential connection between IBD and CRC in a large Korean population. Methods: We conducted a retrospective cohort study using data from the Korean National Health Insurance Service–National Sample Cohort from 2005 to 2019. A total of 9920 CRC patients were matched 1:4 with 39,680 controls using propensity scores based on age, sex, income, and region. Overlap weighting and multivariable logistic regression were used to evaluate the association between IBD and CRC. Subgroup analyses were conducted to assess effect modification by demographic and clinical factors. Results: IBD markedly increased the likelihood of developing CRC (adjusted odds ratio (aOR) = 1.38; 95% confidence interval (CI): 1.20–1.58; p < 0.001), with the association primarily driven by UC (aOR = 1.52; 95% CI: 1.27–1.83). CD appeared unrelated to heightened CRC risk overall, though a significant association was observed among low-income CD patients (aOR = 1.58; 95% CI: 1.15–2.16). The UC–CRC association persisted across all subgroups, including patients without comorbidities. Conclusions: Our findings support an independent association between IBD—particularly UC—and increased CRC risk in Korea. These results underscore the need for personalized CRC surveillance strategies that account for disease subtype, comorbidity burden, and socioeconomic status, especially in vulnerable subpopulations. Full article

Ceftazidime–avibactam (CAZ-AVI) is a second-generation intravenous β-lactam/β-lactamase inhibitor combination. In recent years, substantial evidence has emerged regarding the efficacy and safety of CAZ-AVI. However, data on its use in critically ill patients remain limited. Background/Objectives: This multicenter, retrospective, observational cohort study was conducted across four Intensive Care Units (ICUs) in three hospitals in the Marche region of Italy. The primary objective was to evaluate the 30-day clinical outcomes and identify risk factors associated with 30-day clinical failure—defined as death, microbiological recurrence, or persistence within 30 days after discontinuation of therapy—in critically ill patients treated with CAZ-AVI. Methods: The study included all adult critically ill patients admitted to the participating ICUs between January 2020 and September 2023 who received CAZ-AVI for at least 72 h for the treatment of a confirmed or suspected Gram-negative bacterial (GNB) infection. Results: Among the 161 patients included in the study, CAZ-AVI treatment resulted in a positive clinical outcome (i.e., clinical improvement and 30-day survival) in 58% of cases (n = 93/161), while the overall mortality rate was 24% (n = 38/161). Relapse or persistent infection occurred in a substantial proportion of patients (25%, n = 41/161). Notably, acquired resistance to CAZ-AVI was observed in 26% of these cases, likely due to suboptimal use of the drug in relation to its pharmacokinetic/pharmacodynamic (PK/PD) properties in critically ill patients. Furthermore, treatment failure was more frequent among immunosuppressed individuals, particularly liver transplant recipients. Conclusions: This study demonstrates that the mortality rate among ICU patients treated with this novel antimicrobial combination is consistent with findings from other studies involving heterogeneous populations. However, the rapid emergence of resistance underscores the need for vigilant surveillance and the implementation of robust antimicrobial stewardship strategies. Full article

Background: The COVID-19 pandemic has profoundly altered the clinical and microbiological landscape of respiratory tract infections (RTIs), potentially reshaping pathogen distribution and antimicrobial resistance (AMR) profiles across care settings. Objectives: The objective of this study was to assess temporal trends in respiratory bacterial pathogens, antimicrobial resistance, and polymicrobial infections across three pandemic phases—pre-COVID (2018–2019), COVID (2020–2022), and post-COVID (2022–2024)—in hospitalized and ambulatory patients. Methods: We retrospectively analyzed 1827 respiratory bacterial isolates (hospitalized patients, n = 1032; ambulatory patients, n = 795) collected at a tertiary care center in Northern Italy. Data were stratified by care setting, anatomical site, and pandemic phase. Species identification and susceptibility testing followed EUCAST guidelines. Statistical analysis included chi-square and Fisher’s exact tests. Results: In hospitalized patients, a significant increase in Pseudomonas aeruginosa (from 45.5% pre-COVID to 58.6% post-COVID, p < 0.0001) and Acinetobacter baumannii (from 1.2% to 11.1% during COVID, p < 0.0001) was observed, with 100% extensively drug-resistant (XDR) rates for A. baumannii during the pandemic. Conversely, Staphylococcus aureus significantly declined from 23.6% pre-COVID to 13.7% post-COVID (p = 0.0012). In ambulatory patients, polymicrobial infections peaked at 41.2% during COVID, frequently involving co-isolation of Candida spp. Notably, resistance to benzylpenicillin in Streptococcus pneumoniae reached 80% (4/5 isolates) in hospitalized patients during COVID, and carbapenem-resistant P. aeruginosa (CRPA) significantly increased post-pandemic in ambulatory patients (0% pre-COVID vs. 23.5% post-COVID, p = 0.0014). Conclusions: The pandemic markedly shifted respiratory pathogen dynamics and resistance profiles, with distinct trends observed in hospital and community settings. Persistent resistance phenotypes and frequent polymicrobial infections, particularly involving Candida spp. in outpatients, underscore the need for targeted surveillance and antimicrobial stewardship strategies. Full article

Adverse drug events (ADEs) significantly impact patient safety and health outcomes. Manual ADE detection from clinical narratives is time-consuming, labor-intensive, and costly. Recent advancements in large language models (LLMs), including transformer-based architectures such as Bidirectional Encoder Representations from Transformers (BERT) and Generative Pretrained Transformer (GPT) series, offer promising methods for automating ADE extraction from clinical data. These models have been applied to various aspects of pharmacovigilance and clinical decision support, demonstrating potential in extracting ADE-related information from real-world clinical data. Additionally, chatbot-assisted systems have been explored as tools in clinical management, aiding in medication adherence, patient engagement, and symptom monitoring. This narrative review synthesizes the current state of LLMs in ADE detection from a clinical perspective, organizing studies into categories such as human-facing decision support tools, immune-related ADE detection, cancer-related and non-cancer-related ADE surveillance, and personalized decision support systems. In total, 39 articles were included in this review. Across domains, LLM-driven methods have demonstrated promising performances, often outperforming traditional approaches. However, critical limitations persist, such as domain-specific variability in model performance, interpretability challenges, data quality and privacy concerns, and infrastructure requirements. By addressing these challenges, LLM-based ADE detection could enhance pharmacovigilance practices, improve patient safety outcomes, and optimize clinical workflows. Full article

Background: The long-term clinical and laboratory results of a 33-year follow-up of a Greek family with abetalipoproteinemia (ABL) are described. Case Report: The patients (two brothers and their sister, aged 57, 49, and 62 years, respectively) are still alive, being under close surveillance. In two of the three patients, diarrhea appeared in early infancy, while in the third, it appeared during adolescence. CNS symptomatology worsened after the second decade of life. At the same time, night blindness appeared in the advanced stages of the disease, resulting in almost complete loss of vision in one of the male patients and severe impairment in the other. The diagnosis was based on the clinical picture, ophthalmological findings, serum lipid estimations, and presence of peripheral acanthocytosis. All patients exhibited typical serum lipidemic profile, ophthalmological findings, and acanthocytes in the peripheral blood. During the follow-up period, strict dietary modifications were applied, including the substitution of fat with medium-chain triglycerides (MCT oil). After 33 years since the initial diagnosis, all patients are alive without any sign of liver dysfunction despite continuous use of MCT oil. However, symptoms from the central nervous system and vision impairment worsened. Conclusion: The course of these patients suggests that the application of a modified diet, including MCT oil, along with close surveillance, could prolong the survival of patients without significant side effects from the liver. Full article

Classical Hodgkin lymphoma (cHL) is a biologically and clinically unique malignancy characterized by rare Hodgkin and Reed–Sternberg (HRS) cells surrounded by a dense and diverse inflammatory infiltrate. These malignant cells actively reshape the tumor microenvironment (TME) through metabolic reprogramming and immune evasion strategies. This review synthesizes current knowledge on how metabolic alterations contribute to tumor survival, immune dysfunction, and therapeutic resistance in cHL. We discuss novel therapeutic approaches aimed at disrupting these processes and examine the potential of combining metabolic interventions with immune-based strategies—such as immune checkpoint inhibitors (CPIs), epigenetic modulators, bispecific antibodies, and CAR-T/CAR-NK cell therapies—which may help overcome resistance and enhance anti-tumor responses. Several agents are currently under investigation for their ability to modulate immune cell metabolism and restore effective immune surveillance. Altogether, targeting metabolic vulnerabilities within both tumor and immune compartments offers a promising, multifaceted strategy to improve clinical outcomes in patients with relapsed or refractory cHL. Full article

The global trend of increasing mushroom consumption, combined with traditional practices in Romania and other Eastern European countries of collecting and consuming “wild mushrooms”, may contribute to the rising incidence of emergency presentations due to inedible mushroom poisoning. This study aims to identify the clinical features of mushroom poisoning by retrospectively analyzing 47 cases presented to the Emergency Department of the Bucharest Emergency Hospital between 2023 and 2024. The methodology consists of a retrospective cohort study including all patients presented to the Emergency Department of the Bucharest Emergency Hospital with symptoms following mushroom ingestion between 2023 and 2024 totaling 47 cases. Conclusions: In this cohort, most cases of wild/forest mushroom poisoning (76.59%) were diagnosed during autumn, particularly in September and October. The distribution of cases was uniform with respect to both gender and urban versus rural residence. A significant proportion of patients (74.46%) required hospitalization for surveillance and/or specific treatment. The predominant clinical presentation consisted of gastrointestinal symptoms, observed in 97.87% of cases. Full article

Background/Objectives: Nonoperative management (NOM) of patients with locally advanced rectal cancer (LARC) who achieve a complete clinical response (cCR) to total neoadjuvant therapy (TNT) has been shown to be oncologically safe and is an attractive treatment option for patients. However, identifying responders to TNT that may benefit from nonoperative management is clinically challenging. Circulating tumor DNA (ctDNA) testing has shown promise in detecting minimal residual disease but has not yet been studied extensively within this clinical context. Methods: This is a single-institution retrospective case series study of LARC patients treated with TNT from 2019 to 2023 who underwent ctDNA testing as an adjunct to standard clinical response assessments. Results: A total of 28 patients had ctDNA testing as part of their response assessments after TNT. In total, 9 patients had positive ctDNA, and 19 patients had negative ctDNA during surveillance. Baseline characteristics of these two groups were not different. In this study, 6/9 (67%) patients who had positive ctDNA required surgery for residual rectal cancer, whereas only 4/19 (21%) patients who had negative ctDNA required surgery (p = 0.035). Conclusions: ctDNA testing has the potential to detect MRD in LARC patients treated with TNT. Full article

Background: Patients diagnosed with melanoma are at increased risk of developing multiple primary melanomas (MPMs). Identifying clinical and genetic factors associated with MPM is critical for implementing personalized surveillance strategies. This study aims to describe the clinical, histopathological, and genetic characteristics of patients with MPM managed in a tertiary hospital and to contextualize findings within the current literature. Methods: We conducted a retrospective review of patients diagnosed with two or more primary melanomas between 2010 and 2023 at a tertiary dermatology unit. Demographic data, personal and family cancer history, phototype, melanoma characteristics, genetic testing, staging, treatments, and outcomes were collected. These data were compared with findings from the recent literature. Results: Thirteen patients (ten males, three females; median age: 59 years) were found to have a total of 33 melanomas. Most patients had Fitzpatrick phototype II and no immunosuppression. The number of melanomas per patient ranged from two to five. Synchronous lesions were observed in two patients. Common locations included the trunk and extremities. Histologically, 57% were in situ melanomas, and subsequent melanomas were generally thinner than the index lesion. Two patients showed progression to advanced disease. One patient was positive for MC1R mutation; the rest were negative or inconclusive. Additional phenotypic and environmental risk factors were extracted from patient records and are summarized as follows: Ten patients (76.9%) had Fitzpatrick skin phototype II, and three (23.1%) had phototype III. Chronic occupational sun exposure was reported in four patients (30.8%), while five (38.5%) recalled having suffered multiple sunburns during childhood or adolescence. Eight patients (61.5%) presented with a total nevus count exceeding 50, and five (38.5%) exhibited clinically atypical nevi. None of the patients reported use of tanning beds. Conclusions: Our findings are consistent with the existing literature indicating that patients with MPM often present with thinner subsequent melanomas and require long-term dermatologic follow-up. The inclusion of genetic testing and phenotypic risk factors enables stratified surveillance and supports the application of personalized medicine in melanoma management. Full article

Background/Objectives: Helicobacter pylori (H. pylori) is a common gastric pathogen linked to gastritis, gastroduodenal ulcers, and gastric cancer. Rising antimicrobial resistance (AMR) poses challenges for effective treatment and has prompted the WHO to classify H. pylori as a high-priority pathogen. This study aimed to detect the prevalence of AMR genes in H. pylori-positive gastric samples from patients in Algarve, Portugal, where regional data is scarce. Methods: Eighteen H. pylori-positive gastric biopsy samples from patients undergoing upper gastrointestinal endoscopy were analyzed. PCR and sequencing were used to identify genes associated with resistance to amoxicillin (Pbp1A), metronidazole (rdxA, frxA), tetracycline (16S rRNA mutation) and clarithromycin (23S rRNA). Sequence identity and homologies were verified using tBLASTx and the Comprehensive Antibiotic Resistance Database (CARD). Results: Out of the 18 H. pylori-positive samples, 16 (88.9%) contained at least one AMR gene. The most frequent genes were rdxA (83.3%) and frxA (66.7%) for metronidazole resistance, and the 16S rRNA mutation (66.7%) for tetracycline. Resistance to amoxicillin and clarithromycin was detected in 27.8% and 16.7% of cases, respectively. Most samples (72.2%) had multiple resistance genes. A significantly strong association was found between female sex and the presence of the rdxA gene (p = 0.043). Conclusions: The study reveals a high prevalence of H. pylori resistance genes in Algarve, particularly against metronidazole and tetracycline. These findings highlight the need for local surveillance and tailored treatment strategies. Further research with larger populations is warranted to assess regional resistance patterns and improve eradication efforts. Full article

Locally advanced rectal cancer (LARC) remains a major clinical challenge due to its high risk of local recurrence and distant metastasis. Although total mesorectal excision (TME) has been established as the gold standard surgical approach, high recurrence rates associated with surgery alone have driven the development of multimodal preoperative strategies, such as radiotherapy and chemoradiotherapy. More recently, total neoadjuvant therapy (TNT)—which integrates systemic chemotherapy and radiotherapy prior to surgery—and non-operative management (NOM) for patients who achieve a clinical complete response (cCR) have further expanded treatment options. These advances aim not only to improve oncologic outcomes but also to enhance quality of life (QOL) by reducing long-term morbidity and preserving organ function. However, several unresolved issues persist, including the optimal sequencing of therapies, precise risk stratification, accurate evaluation of treatment response, and effective surveillance protocols for NOM. The advent of molecular biomarkers, next-generation sequencing, and artificial intelligence (AI) presents new opportunities for individualized treatment and more accurate prognostication. This narrative review provides a comprehensive overview of the current status of preoperative treatment for LARC, critically examines emerging strategies and their supporting evidence, and discusses future directions to optimize both oncological and patient-centered outcomes. By integrating clinical, molecular, and technological advances, the management of rectal cancer is moving toward truly personalized medicine. Full article