This study aimed to evaluate the effectiveness and safety of Meropenem-Vaborbactam(M-V) for treating carbapenem-resistant Enterobacterales (CRE) infections based on real-world data. A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was conducted, considering studies up to October 31, 2024. Real-world evidence from registries and nonselected case series involving 10 or more adult patients treated with Meropenem-Vaborbactam for CRE infections was included. Meta-analyses using a random-effects model were performed, with the primary outcomes being clinical efficacy and survival, including 30-day and 90-day survival rates. Out of 1862 potentially relevant publications, six studies were included in the meta-analysis. The pooled clinical success rate was 75% (95% CI, 66%-82%), and the pooled 30-day and 90-day survival rates were 75% (95% CI, 71%-78%) and 69% (95% CI, 61%-76%), respectively. Importantly, no serious adverse effects were reported. In conclusion, Meropenem-Vaborbactam demonstrated both efficacy and safety in treating CRE infections in real-world settings. This study was registered with PROSPERO (CRD42022370880).

Doxorubicin (DOX) and lapatinib (LAP) have been reported to cause liver toxicity. The roles of mitochondrial and cellular responses in DOX and LAP mediated-hepatotoxicity have not been investigated with or without quercetin (QUE) in HepG2 cells sensitive to mitochondrial damage (high-glucose or galactose media) in addition to studies. Our results revealed that cytosolic pathways might play role a in DOX-induced cytotoxicity rather than mitochondria. QUE exacerbated DOX-induced ATP depletion in both environments. Our data also indicated that cytosolic and mitochondrial pathways might play a role in LAP-induced cytotoxicity. Incubating QUE with LAP increased ATP levels in high-glucose media. Therefore, QUE might have protective effect against LAP-induced cytotoxicity resulting from cytosolic pathways. The findings from experiments that QUE increased DOX or LAP-induced mitochondrial dysfunction were confirmed by the results from studies indicating that QUE incubated with LAP or DOX might increase mitochondrial dysfunction.

To search for key drug resistance biomarkers and potential chemotherapeutic agents for combination therapy in melanoma patients. The common up-regulated differentially expressed genes were acquired from two cohort studies, GSE91061 and PRJEB23709. Univariate and multivariate Cox regression survival analyses were performed to screen for important prognostic biomarkers. A multi-gene panel including , , and , not only plays an important role in prognostic indicators, but also in predicting the probability of resistance to anti-PD-1 in patients with melanoma. Chemotherapy drug response models found five potential drugs, including all-trans retinoic acid, doxorubicin, etoposide, methotrexate and MG-132, were significantly associated with target genes in gene-panel. Molecular docking confirmed that potential drugs have good binding ability to target genes , and suggesting that the multi-gene panel is expected to provide assistance for drug resistance prediction and prognosis assessment and combination therapy in patients with anti-PD-1 resistant melanoma.

This study evaluated SARS-CoV-2 infection impacts on clinical characteristics, antibody levels, and immune responses in 100 malignant hematological tumor patients. Laboratory assessments included hematological, biochemical, and inflammatory markers. Multivariable analysis identified age (OR = 1.56, p = 0.004), chemotherapy cycles (OR = 1.86, p < 0.001), comorbidities (OR = 3.15, p = 0.015), WBC count (OR = 1.79, p = 0.016), CRP (OR = 2.07, p = 0.007), ferritin (OR = 1.22, p = 0.035), IL-6 (OR = 1.59, p = 0.001), IgG (OR = 2.28, p = 0.037), CD8+ T cells (OR = 2.97, p = 0.005), and NK cells (OR = 0.80, p = 0.019) as COVID-19 risk factors. COVID-19 patients showed significantly higher hospitalization (30.77% vs 10.42%, p = 0.007), ICU admission (23.08% vs 6.25%, p = 0.019), and lower 1-year survival (59.62% vs 87.50%, p = 0.002) versus controls. SARS-CoV-2 infection induces hematological/immune alterations and worsens clinical outcomes in hematological malignancy patients, emphasizing their heightened vulnerability.

Although recent advancements in cancer treatment have significantly improved survival rates, they have also raised concerns regarding severe adverse effects, including cardiotoxicity. We conducted a prospective study at Dayanand Medical College and Hospital, Ludhiana to assess chemotherapy-related cardiac dysfunction in newly diagnosed, histologically confirmed breast cancer cases. Among 97 breast cancer patients undergoing chemotherapy, 13 (13.4%) developed left ventricular dysfunction (LVD), predominantly in younger patients with left-sided breast involvement (64.9%). A significant association was found between estrogen receptor (ER) positivity and LVD risk (P = 0.03), with 15.4% of LVD patients also being hypertensive. The incidence of LVD was notably high at 38.5% among patients receiving trastuzumab, while cumulative doses of doxorubicin and cyclophosphamide did not show significant correlation with LVD. Recovery was promising, with 76.9% of affected patients demonstrating significant improvement post-treatment. These findings highlight the need for continuous cardiac monitoring and personalized treatment strategies to mitigate LVD risk.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are associated with immune-related adverse events (irAEs). Pembrolizumab, an anti-PD-1 antibody, is widely used in non-small cell lung cancer (NSCLC), yet immune thrombocytopenia remains a rare but potentially fatal complication. We report a case of a 55-year-old male with metastatic NSCLC who developed pembrolizumab-associated immune thrombocytopenia. The patient initially responded well to combination therapy with pembrolizumab, carboplatin, and pemetrexed, achieving a metabolic complete response. However, after several cycles, he experienced recurrent grade 3 thrombocytopenia. Immune thrombocytopenia was suspected and managed with corticosteroids, leading to platelet recovery. Upon pembrolizumab rechallenge, thrombocytopenia recurred, necessitating permanent discontinuation of pembrolizumab while continuing pemetrexed maintenance. This case underscores the need for early recognition and prompt management of ICI-induced thrombocytopenia to ensure patient safety while optimizing oncologic outcomes.

This study aimed to evaluate the compatibility of generic ceftriaxone sodium preparations with various rubber closures used in pharmaceutical packaging, focusing on the release of butylated hydroxytoluene (BHT), an antioxidant present in rubber closures that may migrate into drug products. BHT levels were quantified using gas chromatography-mass spectrometry (GC-MS) to assess stability and safety. Results showed that all samples contained BHT, with concentrations ranging from below the quantification limit to a maximum of 5.65 ppm. Notably, 47.62% of the samples exceeded the threshold of toxicological concern (TTC) of 1.5 µg/day, raising significant safety concerns. Older samples exhibited higher BHT levels, and products from pharmacies generally had greater concentrations than those obtained from manufacturers. These findings underscore the critical importance of assessing interactions between drug formulations and packaging materials, emphasizing the need for rigorous quality control in injectable pharmaceuticals. Future research should explore strategies to mitigate BHT accumulation in these preparations.

The incidence of endometrial cancer (EC), a widely prevalent gynecological malignancy, is witnessing a global surge. Although early-stage cancer demonstrates promising outcomes, advanced cancer is associated with an unfavorable prognosis. Nevertheless, for specific pathological types or molecular subtypes of advanced EC, an accurate treatment algorithm can lead to a favorable prognosis. Here, we report a case of stage IVB EC characterized by mucinous differentiation with mismatch repair deficiencies (MMRd) who was successfully treated with combination of oxaliplatin and programmed cell death protein 1 (PD-1) inhibitor. Our findings emphasize the importance of conducting pathological and molecular typing assessments in individuals with advanced stage or recurrent EC. Additionally, combining oxaliplatin and PD-1 inhibitors may be a viable treatment option for EC with mucinous differentiation and MMRd. More representative and standardized studies are needed to consolidate this conclusion.

Immunotherapies have increased the therapeutic options for patients with metastatic renal cell carcinoma (mRCC), but the absence of prognostic indicators remains unresolved. We assessed the potential association of BMI with the overall survival (OS) of patients treated with nivolumab.

As a systematic review, this study addresses a gap in the literature by evaluating both the short-term and long-term outcomes of breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The purpose of the current study was to evaluate NAC's impact on breast cancer patients' surgical outcomes. We performed a comprehensive search of international databases, including PubMed, Scopus, Embase, and Science Direct, covering studies from 2000 to 2023, using carefully selected keywords. Our search strategy aimed to capture a wide variety of relevant studies. To ensure a structured and unbiased selection, we followed PRISMA guidelines throughout the process. We concentrated on identifying studies that reported on short-term outcomes, like surgical complications (e.g., operation time, blood loss), as well as long-term outcomes, including overall survival, tumor size reduction, metastasis rates, breast conservation surgery, and recurrence rates. The findings highlighted the benefits of NAC in terms of lower recurrence and metastasis rates. The results also emphasized the significance of considering tumor characteristics and nodal involvement for prognostication in this patient population. The findings of this study will contribute to a better understanding of the impact of NAC on surgical outcomes in breast cancer patients, providing valuable insights for treatment planning and optimizing patient care.

Immune checkpoint inhibitors (ICIs) have shown promise in the treatment of gastric and oesophageal cancers (GEC). Despite their promising efficacy, ICIs have been associated with unique side effects known as immune-related adverse events (IRAEs). Several studies have shown improved treatment responses in patients with IRAEs compared to those without IRAEs in various cancer types such as melanoma and non-small cell lung cancer. We performed a single-institution retrospective study to characterize IRAE incidence and association with treatment response in advanced GEC. We identified 70 patients with GEC who received ICI therapy; 20 (29%) developed an IRAE of any magnitude. The most common were colitis (35%) hypothyroidism (25%) and pneumonitis (20%). Median PFS and OS were not statistically different between IRAE and nonIRAE groups (10.4 vs. 11.3 months  = 0.6 and 11.0 vs. 12.9 months  = 1.0, respectively). This is in contrast to studies in other cancer types that have suggested association between IRAE and improved outcomes.

We review the case of a 58-year-old female on extracorporeal membrane oxygenation (ECMO) support diagnosed with invasive pulmonary aspergillosis (IPA). Intravenous isavuconazole was started, requiring dose escalation to achieve isavuconazole trough concentration (ISA-Cmin) within the therapeutic range (2.5-5.0 μg/mL). For more than 4 months, she maintained a dose of 200 mg q12h, with a median ISA-Cmin of 3.4 (interquartile range [IQR]: 3.1-4.9) µg/mL. Throughout this interval, 17 assessments of ISA-Cmin were performed (weekly). Of these, 82% (14/17) were within the therapeutic range, with an intra-individual variability of 36.8%. Although no signs of hepatotoxicity were observed, she experienced short-term gastrointestinal adverse events related to potential isavuconazole over-exposure (ISA-Cmin > 5.0 μg/mL). ECMO circuit changes did not appear to affect ISA-Cmin. She was not obese (IMC ≈ 25 kg/m) and did not require other extracorporeal therapy, but hypoalbuminemia may have contributed to an increase in unbound isavuconazole fraction and consequently its clearance.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are the recommended front-line therapy for treatment-naïve patients with advanced stage EGFR mutated Non-Small Cell Lung Cancer (NSCLC), with better tolerance and outcomes compared to chemotherapy. However, patients inevitably develop resistance to EGFR-TKI. The extent of progression free survival depends on intrinsic or acquired on-target/off-target mechanisms of EGFR-TKI resistance. Overcoming these acquired rearrangements remains challenging in modern precision medicine. In case of disease progression during treatment with an EGFR-TKI, rebiopsy is recommended to search for a potential resistance mechanism. However, the therapeutic potential of these resistance mechanisms represents an unmet need in thoracic oncology. We present a case of a 78-year-old woman with stage IVB EGFR-mutated NSCLC in whom an acquired RET Gene Fusion was identified as the -independent resistance mechanism. Additionally, a combined therapy of Osimertinib and Selpercatinib showed a durable oncological response with 14 months of progression free survival in the absence of adverse events. Addition of Selpercatinib to Osimertinib in an EGFR-mutated NSCLC patient with an acquired RET fusion was well tolerated and created a clinical benefit. Further prospective investigation into these novel combination strategies is needed as resistance mechanisms could serve as possible targets for new therapy approaches.

This retrospective study investigated whether piperacillin/tazobactam (PIPC/TAZ) monotherapy affects renal function compared to cefepime (CFPM) or meropenem (MEPM) monotherapy. Hospitalized patients who received PIPC/TAZ, CFPM, or MEPM monotherapy between April 2021 and December 2022 were enrolled in this study. We used inverse probability of treatment weighting (IPTW) to balance baseline characteristics and compare the incidence of acute kidney injury (AKI). Overall, 259, 104, and 98 patients were enrolled in the PIPC/TAZ, CFPM, and MEPM groups, respectively. After applying IPTW, PIPC/TAZ administration was found to be significantly associated with an increased risk of AKI (odds ratio [OR]: 6.75, 95% confidence interval [CI]: 1.30-34.8,  = 0.023 compared to CFPM; and OR: 7.71, 95% CI: 1.00-59.2,  = 0.049 compared to MEPM). PIPC/TAZ monotherapy may be associated with a higher risk of AKI than CFPM or MEPM monotherapy.

Cervical cancer is one of the most common gynecologic malignancies worldwide. 5-Fluorouracil (5-Fu) is a widely used anticancer drug for various cancers, but the development of 5-Fu resistance poses a challenge in treating cervical cancer patients. This study examined the roles and molecular mechanisms of LncRNA-FGD5-AS1 in 5-Fu resistant cervical cancer cells through in vitro and in vivo experiments. We discovered FGD5-AS1 and the RNA methylation reader protein, YTHDF2, were positively associated with 5-Fu resistance in cervical cancer. A positive correlation between FGD5-AS1 and YTHDF2 was found in cervical tumor tissues. Expressions of FGD5-AS1 and YTHDF2 were significantly upregulated in the established 5-Fu resistant cervical cancer cells. MiRNA-microArray analysis screened that FGD5-AS1 downregulated miR-130a-3p expression in cervical cancer cells. Subsequently, we demonstrated FGD5-AS1 acted as a ceRNA by sponging miR-130a-3p, which targeted the 3'UTR of YTHDF2 mRNA. Rescue experiments validated overexpression of FGD5-AS1 increased 5-Fu resistance in cervical cancer cells, which was reversed by miR-130a-3p overexpression. Finally, combining FGD5-AS1 silencing with 5-Fu treatments resulted in a synergistic inhibitory effect (CI < 1) on the viability of cervical cancer cells. This study reveals a FGD5-AS1-miR-130a-3p-YTHDF2 axis that could be a promising therapeutic target for overcoming 5-Fu resistance in cervical cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. LncRNA NORAD is frequently upregulated and positively associated with various cancer progressions. We discovered NORAD was significantly upregulated in CRC tissues and cells. NORAD sponged miR-106a-5p to form a ceRNA complex. MiR-106a-5p was remarkedly downregulated in CRC tumors and cells. Silencing NORAD or overexpression of miR-106a-5p effectively increased cisplatin sensitivity. In the established cisplatin resistant cell line, NORAD was upregulated and miR-106a-5p was downregulated. Furthermore, we disclosed miR-106a-5p directly targeted 3'UTR of CCND1, which is an important cell cycle regulator and is frequently overexpressed in human cancers. Rescue experiments showed restoration of CCND1 in miR-106a-5p-overexpressing CRC cells successfully recovered cisplatin resistance. Finally, restoration of miR-106a-5p in NORAD-overexpressing CRC cells re-sensitized cisplatin resistance by targeting CCND1. Summarily, this study uncovered a NORAD-promoted cisplatin resistance through modulating the miR-106a-5p-CCND1 axis, contributing to developing novel therapy for treating chemoresistant CRC.

Anti-tumor drugs cause hand-foot syndrome through a variety of pathogenic mechanisms. Some chemotherapeutic medications that can cause HFS include 5FU, doxorubicin, capecitabine, high dose cytarabine, and others. These medications each have a unique mechanism resulting in HFS. The histopathological characteristics, clinical manifestations, and variations in gender, ethnicity, or genetic makeup might also impact the development of HFS as an adverse drug reaction. Even though the disease might not become life-threatening, it is nevertheless vital to manage it with therapeutic interventions or by withholding the medication in order to enhance the patient's outcome. Current developments in pharmacological and non-pharmacological therapeutic approaches for managing symptoms also emphasis the same.

To promote the accurate administration of linezolid, this study aimed to evaluate its dosage regimens in critically ill patients with varying renal functions. This evaluation was based on a combined analysis of pharmacokinetic (PK), pharmacodynamic (PD), and toxicodynamic (TD) indices. The percentage of therapeutic target attainment (PTTA) was used as the index for PK/PD/TD, defined as simultaneously meeting two PK/PD criteria (AUC/MIC ≥ 100 and C between 2.6-7.8 mg/L) and adjusted for toxicity probability, with MICs ranging from 0.5 to 8 mg/L. The recommended doses of linezolid for patients: 600 mg every 12 h for normal renal function or mild renal impairment, 300 mg every 12 h for severe renal impairment, 450 mg every 12 h for moderate renal impairment, and 600 mg every 8 h for supra-normal renal function. In conclusion, specific dosing regimens should be adopted for patients with varying renal functions, combined with therapeutic drug monitoring, to ensure the safety and efficacy of linezolid.

Immunotherapy has been advanced through multiple approaches, including immunogenic cytokines, monoclonal antibodies, therapeutic vaccinations, adoptive cell transfer, stem cell transplantation, and oncolytic viruses. This review analyses various strategies in genomics, transcriptomics, single-cell techniques, computational analysis, big data, and imaging technologies for the identification of tumour microbiota and microenvironments. Immunotherapy is becoming acknowledged as a feasible cancer treatment method, facilitating innovative cancer medicines and personalized medicine techniques.

Novel therapeutic interventions are required to address the critical antimicrobial resistance caused by multidrug-resistant (MDR-PA) infections. This study examines the impact of combining delafloxacin with antibiotics on MDR-PA isolated from various samples. The minimum inhibitory concentrations (MICs) of delafloxacin, alone and in combination with other antibiotics, were determined against forty distinct MDR-PA isolates using the broth microdilution method. Time-kill curve assays were used to determine the bactericidal and synergistic effects of delafloxacin alone and in combination with other antibiotics against the selected five strains. Our studies showed delafloxacin exhibited four times greater in-vitro activity against MDR-PA strains than levofloxacin compared with both MIC and MIC results. Delafloxacin + tobramycin and delafloxacin + ceftazidime/avibactam showed synergy in two out of five strains tested at concentrations equal to the MIC. The outcomes of this research also suggest that these combinations may replace therapy for MDR-PA strains.

Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer represents the most prevalent subtype of breast cancer. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, in combination with endocrine therapy (ET), have shown substantial benefits in improving progression-free survival and, for ribociclib, an overall survival advantage. Despite clinical benefits, ribociclib is associated with elevated liver enzymes and severe liver dysfunction. We present a 44-year-old Caucasian woman with HR-positive, HER2-negative metastatic breast cancer who developed drug-induced autoimmune-like hepatitis (DI-ALH) after ribociclib therapy. Initially treated for early-stage disease with surgery, chemotherapy, radiotherapy, and ET, she progressed to metastatic disease and received ribociclib, letrozole, and goserelin, achieving a partial response. Treatment was complicated by grade 3 hepatotoxicity, confirmed as DI-ALH by liver biopsy. Managed with prednisolone and azathioprine, ribociclib was reintroduced at a reduced dose and later escalated to full dose. This case report highlights the importance of a multidisciplinary approach to balance oncologic efficacy with hepatologic safety.