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Bioconjugate Chemistry Jul 2024Currently, there is no effective treatment for glioblastoma multiforme (GBM), the most frequent and malignant type of brain tumor. The blood-brain (tumor) barrier...
Currently, there is no effective treatment for glioblastoma multiforme (GBM), the most frequent and malignant type of brain tumor. The blood-brain (tumor) barrier (BB(T)B), which is composed of tightly connected endothelial cells and pericytes (with partial vasculature collapse), hampers nanomedicine accumulation in tumor tissues. We aimed to explore the effect of nanomedicine size on passive targeting of GBM. A series of size-tunable poly(ethylene glycol) (PEG)-grafted copolymers (gPEGs) were constructed with hydrodynamic diameters of 8-30 nm. Biodistribution studies using orthotopic brain tumor-bearing mice revealed that gPEG brain tumor accumulation was maximized at 10 nm with ∼14 dose %/g of tumor, which was 19 times higher than that in the normal brain region and 4.2 times higher than that of 30-nm gPEG. Notably, 10-nm gPEG exhibited substantially higher brain tumor accumulation than 11-nm linear PEG owing to the prolonged blood circulation property of gPEGs, which is derived from a densely PEG-packed structure. 10 nm gPEG exhibited deeper penetration into the brain tumor tissue than the larger gPEGs did (>10 nm). This study demonstrates, for the first time, the great potential of a nanomedicine downsizing strategy for passive GBM targeting.
PubMed: 38959052
DOI: 10.1021/acs.bioconjchem.4c00235 -
La Radiologia Medica Jul 2024Microwave ablation (MWA) and conventional transarterial chemoembolization (cTACE) are locoregional treatments commonly performed in very early, early and intermediate...
PURPOSE
Microwave ablation (MWA) and conventional transarterial chemoembolization (cTACE) are locoregional treatments commonly performed in very early, early and intermediate stages of hepatocellular carcinoma (HCC). Despite combined locoregional approaches have shown encouraging results in obtaining complete tumor necrosis, their application in a single session is poorly described. Our aim was to evaluate the safety and efficacy of single-session MWA and cTACE treatment in 5-cm HCCs and its influence on liver function.
MATERIALS AND METHODS
All 5-cm HCCs treated by MWA and cTACE performed in a single-session in our Interventional Radiology unit between January 2020 and December 2022 were retrospectively recorded and analyzed. Patients with poor or missing pre- and post-treatment imaging were excluded. Technical success, clinical success, and complications rate were examined as primary endpoints. Pre- and post-treatment liver function laboratory parameters were also evaluated.
RESULTS
A total of 15 lesions (mean lesion diameter, 5.0 ± 1.4 cm) in 15 patients (11 men; mean age, 67.1 ± 8.9 years) were retrospectively evaluated. Technical and clinical success were 100% and 73%, respectively. Four (27%) cases of partial response and no cases of progressive or stable disease were recorded. AST and ALT values have found to be significantly higher in post-treatment laboratory tests. No other significant differences between pre- and post-treatment laboratory values were registered. AST and ALT pre- and post-treatment higher differences (ΔAST and ΔALT) were significantly associated with a lower clinical success rate.
CONCLUSION
MWA and cTACE single-session approach is safe and effective for 5-cm HCCs, without significant liver function impairment. A post-treatment increase in AST and ALT values may be a predictor for clinical failure.
PubMed: 38958915
DOI: 10.1007/s11547-024-01842-7 -
Advances in Therapy Jul 2024For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or...
Real-World Treatment Patterns and Clinical Outcomes Among Patients with Metastatic or Unresectable EGFR-Mutated Non-Small Cell Lung Cancer Previously Treated with Osimertinib and Platinum-Based Chemotherapy.
INTRODUCTION
For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after osimertinib and platinum-based chemotherapy (PBC), no uniformly accepted standard of care exists. Moreover, limited efficacy of standard treatments indicates an unmet medical need, which is being addressed by ongoing clinical investigations, including the HERTHENA-Lung01 (NCT04619004) study of patritumab deruxtecan (HER3‑DXd). However, because limited information is available on real-world clinical outcomes in such patients, early-phase trials of investigational therapies lack sufficient context for comparison. This study describes the real-world clinical characteristics, treatments, and outcomes for patients with EGFRm mNSCLC who initiated a new line of therapy following previous osimertinib and PBC, including a subset matched to the HERTHENA-Lung01 population.
METHODS
This retrospective analysis used a US database derived from deidentified electronic health records. The reference cohort included patients with EGFRm mNSCLC who had initiated a new line of therapy between November 13, 2015 and June 30, 2021, following prior osimertinib and PBC. A subset of patients resembling the HERTHENA-Lung01 population was then extracted from the reference cohort; this matched subset was optimized using propensity score (PS) weighting. Endpoints were real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Confirmed real-world objective response rate (rwORR; partial/complete response confirmed ≥ 28 days later) was calculated for the response-evaluable subgroups of patients (with ≥ 2 response assessments spaced ≥ 28 days apart).
RESULTS
In the reference cohort (N = 273), multiple treatment regimens were used, and none was predominant. Median rwPFS and rwOS were 3.3 and 8.6 months, respectively; confirmed rwORR (response evaluable, n = 123) was 13.0%. In the matched subset (n = 126), after PS weighting, median rwPFS and rwOS were 4.2 and 9.1 months, respectively; confirmed rwORR (response evaluable, n = 57) was 14.1%.
CONCLUSION
The treatment landscape for this heavily pretreated population of patients with EGFRm mNSCLC is fragmented, with no uniformly accepted standard of care. A high unmet need exists for therapeutic options that provide meaningful improvements in clinical benefit.
PubMed: 38958845
DOI: 10.1007/s12325-024-02936-4 -
Mycopathologia Jul 2024The genus Aspergillus consists of a vast number of medically and environmentally relevant species. Aspergillus species classified in series Versicolores are ubiquitous...
The genus Aspergillus consists of a vast number of medically and environmentally relevant species. Aspergillus species classified in series Versicolores are ubiquitous in the environment and include the opportunistic pathogen Aspergillus sydowii, which is associated with onychomycosis and superficial skin infections. Despite frequent clinical reports of A. sydowii and related series Versicolores species, antifungal susceptibility data are scarce, hampering optimal treatment choices and subsequent patient outcomes. Here, we employed antifungal susceptibility testing (AFST) based on microbroth dilution on a set of 155 series Versicolores strains using the common antifungals amphotericin B, itraconazole, voriconazole, posaconazole, isavuconazole and micafungin with the addition of luliconazole and olorofim. All strains were identified using partial calmodulin gene sequencing, with 145 being A. sydowii, seven A. creber and three A. versicolor, using the latest taxonomic insights. Overall, tested antifungals were potent against the entire strain collection. In comparison to A. fumigatus, azole and amphotericin B MICs were slightly elevated for some strains. AFST with luliconazole and olorofim, here reported for the first time, displayed the highest in vitro activity, making these antifungals interesting alternative drugs but clinical studies are warranted for future therapeutic use.
Topics: Antifungal Agents; Microbial Sensitivity Tests; Aspergillus; Humans; Aspergillosis; Environmental Microbiology; Calmodulin; Sequence Analysis, DNA; Acetamides; Piperazines; Pyrimidines; Pyrroles
PubMed: 38958798
DOI: 10.1007/s11046-024-00869-8 -
World Journal of Urology Jul 2024Single-Port Robot-Assisted Partial Nephrectomy (SP-RAPN) can be performed by transperitoneal and retroperitoneal approaches. However, there is a lack of surgical... (Comparative Study)
Comparative Study
PURPOSE
Single-Port Robot-Assisted Partial Nephrectomy (SP-RAPN) can be performed by transperitoneal and retroperitoneal approaches. However, there is a lack of surgical outcomes for novel Retroperitoneal Low Anterior Access (LAA) in SP-RAPN. The study compared outcomes of the standard approach (SA), considering transperitoneal (TP) and posterior retroperitoneal (RP) access vs LAA in SP-RAPN series.
METHODS
102 consecutive patients underwent SP-RAPN between 2019 and 2023 at a tertiary referral robotic center were identified. Baseline characteristics, peri- and post-operative outcomes were collected. Patients were stratified according to surgical approach into standard (RP or TP) vs LAA and, subsequently, RP vs LAA. Multivariable logistic regression analysis was used to test the probability of the same-day discharge adjusting for comorbidity indexes.
RESULTS
Overall, 102 consecutive patients were included in this study (68 SA - 26 TP and 42 posterior RP vs 34 LAA). Median age was 60 (IQR 51.5-66) years and median BMI was 31 (IQR 26.3-37.6). No baseline differences were observed. LAA exhibited significantly shorter length of stay (LOS) (median 10 [IQR 8-12] vs 24 [IQR 12-30.2.] hours, p < .0001), reduced post-operative pain (p < .0001) and decreased narcotic use on 0-1 PO Day (p < .001) compared to SA and RP only. Multivariate analysis, adjusting for comorbidities, identified LAA as a strong predictor for Same-Day Discharge.
CONCLUSION
LAA is an effective approach as well as RP and TP, regardless of the renal mass location, whether it is anterior or posterior, upper/mid or lower pole, yielding favorable outcomes in LOS, post-operative pain and decreased narcotics use compared to SA in SP-RAPN.
Topics: Humans; Nephrectomy; Middle Aged; Male; Female; Robotic Surgical Procedures; Aged; Retroperitoneal Space; Treatment Outcome; Retrospective Studies; Peritoneum; Kidney Neoplasms
PubMed: 38958744
DOI: 10.1007/s00345-024-05096-w -
Neoplasma Jun 2024Currently, there is a lack of effective second-line and subsequent treatments for patients with extensive-stage small-cell lung cancer (ES-SCLC), and the establishment...
Currently, there is a lack of effective second-line and subsequent treatments for patients with extensive-stage small-cell lung cancer (ES-SCLC), and the establishment of a standardized treatment protocol is still underway. Considering the potential synergistic therapeutic effects of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs), combination therapy could be a viable option for treating lung cancer. This research concentrates on assessing the efficacy and safety of anlotinib in combination with ICIs for the treatment of ES-SCLC. We undertook a retrospective analysis of patients with extensive-stage SCLC who received anlotinib in combination with ICIs as second-line and subsequent treatment at Zhejiang Cancer Hospital between April 2020 and April 2023. Survival rates were analyzed using the Kaplan-Meier method. Among the 43 patients who received combination therapy, there were no cases of complete response (CR), 16 patients who achieved partial response (PR), 21 patients who had stable disease (SD), and 6 patients who experienced disease progression (PD). This resulted in an overall response rate (ORR) of 37.2% (16/43) and a disease control rate (DCR) of 86.0% (34/43). The median progression-free survival (PFS) was 4.0 months (95% CI: 2.74-5.26), and the median overall survival (OS) time was 10 months (95% CI: 4.8-15.2). Cox multifactorial regression analysis disclosed that the performance score (PS) and the number of metastatic organs were independent factors influencing PFS in ES-SCLC (p<0.001). The combination therapy demonstrated acceptable toxicity, with a total grade 3/4 toxicity rate of 30.2%. The combination therapy showed a notable association with several adverse events, including hand-foot syndrome, hypertension, and fatigue, which were the most significant. Combining anlotinib with immune checkpoint inhibitors has demonstrated favorable efficacy and safety in the treatment of second-line and subsequent extensive-stage small-cell lung cancer.
Topics: Humans; Small Cell Lung Carcinoma; Indoles; Immune Checkpoint Inhibitors; Quinolines; Male; Female; Lung Neoplasms; Middle Aged; Retrospective Studies; Aged; Antineoplastic Combined Chemotherapy Protocols; Adult; Survival Rate; Progression-Free Survival; Neoplasm Staging; Aged, 80 and over
PubMed: 38958712
DOI: 10.4149/neo_2024_231104N572 -
European Radiology Jul 2024To assess radiopalmar ganglion cysts' (RPG) prevalence, morphology, and clinical significance in consecutive patients.
OBJECTIVES
To assess radiopalmar ganglion cysts' (RPG) prevalence, morphology, and clinical significance in consecutive patients.
MATERIALS AND METHODS
In this retrospective single-center study, two radiologists assessed the presence of RPG and morphologic features on wrist MRI. Radiopalmar complaints and scapholunate ligament (SLL) tears were evaluated.
RESULTS
A total of 1053 wrists in 909 patients (mean age 43.4 ± 15.5 years, 602 females) were evaluated. All 308 RPG (Group 1; 308 patients, 29.2%) originated from the palmar capsule; 49 were unilocular, 95 oligolocular, and 164 multilocular; 745 wrists had no RPG (Group 2; 601 patients). One hundred and twenty-six RPG showed internal debris. The mean diameter was 8.5 ± 5.6 mm (cranio-caudal) (1.0-32.9 mm), 8.0 ± 4.1 mm (medio-lateral) (1.0-31.9 mm), and 3.7 ± 2.3 mm (dorso-palmar) (0.4-16.0 mm). 168 RPG showed direct contact with the radial vascular bundle, 24 with the flexor carpi radialis tendon, and 123 with the flexor pollicis longus tendon. In Group 1, significantly more patients showed partial (82/308) [group 2: 45/745, p < 0.001] or complete SLL tears (22/308) [group 2: 20/745, p < 0.001]. Of the patients with RPG, 15.3% presented with radiopalmar complaints. Only the dorso-palmar RPG diameter was positively correlated with radiopalmar complaints (for readers 1 and 2: r = 0.66/0.61, p < 0.001, respectively), and the best dorso-palmar diameter cut-off value for the probability of having radiopalmar complaints was defined at 3 mm (area under the curve (AUC) 0.74). Other morphologic features were not eligible to discriminate symptomatic patients (AUC range 0.53-0.61).
CONCLUSION
This study found RPG in 29% of patients, most of them asymptomatic. However, a dorso-palmar cyst diameter > 3 mm may be clinically significant.
CLINICAL RELEVANCE STATEMENT
Radiopalmar ganglion cysts, observed in 29% of wrist MR examinations, are mostly asymptomatic, but those with a larger dorso-palmar diameter may be associated with radiopalmar complaints.
KEY POINTS
Radiopalmar ganglion cysts are found in 29% of patients undergoing wrist MRI. Most patients with evidence of radiopalmar ganglion cysts do not show radiopalmar symptoms (85%). A dorso-palmar cyst diameter > 3 mm may be associated with radiopalmar complaints.
PubMed: 38958696
DOI: 10.1007/s00330-024-10884-4 -
MBio Jul 2024The physiology and ecology of particle-associated marine bacteria are of growing interest, but our knowledge of their aggregation behavior and mechanisms controlling...
UNLABELLED
The physiology and ecology of particle-associated marine bacteria are of growing interest, but our knowledge of their aggregation behavior and mechanisms controlling their association with particles remains limited. We have found that a particle-associated isolate, sp. ALT199 strain 4B03, and the related type-strain 27126 both form large (>500 μm) aggregates while growing in rich medium. A non-clumping variant (NCV) of 4B03 spontaneously arose in the lab, and whole-genome sequencing revealed a partial deletion in the gene encoding UDP-glucose-4-epimerase (308-324). In 27126, a knock-out of (::km) resulted in a loss of aggregation, mimicking the NCV. Microscopic analysis shows that both 4B03 and 27126 rapidly form large aggregates, whereas their respective mutants remain primarily as single planktonic cells or clusters of a few cells. Strains 4B03 and 27126 also form aggregates with chitin particles, but their mutants do not. Alcian Blue staining shows that 4B03 and 27126 produce large transparent exopolymer particles (TEP), but their mutants are deficient in this regard. This study demonstrates the capabilities of cell-cell aggregation, aggregation of chitin particles, and production of TEP in strains of , a widespread particle-associated genus of heterotrophic marine bacteria. A genetic requirement for is evident for each of the above capabilities, expanding the known breadth of requirement for this gene in biofilm-related processes.
IMPORTANCE
Heterotrophic marine bacteria have a central role in the global carbon cycle. Well-known for releasing CO2 by decomposition and respiration, they may also contribute to particulate organic matter (POM) aggregation, which can promote CO2 sequestration via the formation of marine snow. We find that two members of the prevalent particle-associated genus can form aggregates comprising cells alone or cells and chitin particles, indicating their ability to drive POM aggregation. In line with their multivalent aggregation capability, both strains produce TEP, an excreted polysaccharide central to POM aggregation in the ocean. We demonstrate a genetic requirement for in aggregation and large TEP formation, building our mechanistic understanding of these aggregative capabilities. These findings point toward a role for heterotrophic bacteria in POM aggregation in the ocean and support broader efforts to understand bacterial controls on the global carbon cycle based on microbial activities, community structure, and meta-omic profiling.
PubMed: 38958440
DOI: 10.1128/mbio.00038-24 -
Turkiye Parazitolojii Dergisi Jun 2024is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic...
OBJECTIVE
is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic disease, but there is a need for new drugs since 1980's with increasing numbers of reported resistance. In this study, it was aimed to determine the antitrichomonal activity of the major components of (cinnamon) and (thyme) essential oils, cinnamaldehyde, carvacrol and thymol against metronidazole resistant and susceptible strains, and to determine their interaction with metronidazole by checkerboard method.
METHODS
Cinnamaldehyde, carvacrol, thymol and metronidazole were obtained commercially. Two clinical isolates and one metronidazole resistant reference strain were used in the study. MIC50 and MLC values of essential oil components and metronidazole were determined by broth microdilution method. The combinations of essential oil components with metronidazole were determined by the checkerboard method.
RESULTS
According to activity tests, cinnamaldehyde was determined to be most effective essential oil component. Clinical isolates were susceptible to metronidazole. In combination study, metronidazole showed synergy with cinnamaldehyde and carvacrol, and partial synergy with thymol.
CONCLUSION
It was determined that cinnamaldehyde, carvacrol and thymol, which are known to have high antimicrobial activity, also have strong activity against isolates and show a synergistic interaction with metronidazole. The use of metronidazole at lower doses in the synergistic interaction may contribute to the literature in terms of reducing drug side effects, creating a versatile antimicrobial target, and reducing the rate of resistance development.
Topics: Acrolein; Thymol; Cymenes; Drug Synergism; Metronidazole; Humans; Oils, Volatile; Thymus Plant; Trichomonas vaginalis; Monoterpenes; Female; Cinnamomum zeylanicum; Antiprotozoal Agents; Microbial Sensitivity Tests; Drug Resistance
PubMed: 38958374
DOI: 10.4274/tpd.galenos.2024.91855 -
ACS Nano Jul 2024Phonon engineering at the nanoscale holds immense promise for a myriad of applications. However, the design of phononic devices continues to rely on regular shapes...
Phonon engineering at the nanoscale holds immense promise for a myriad of applications. However, the design of phononic devices continues to rely on regular shapes chosen according to long-established simple rules. Here, we demonstrate an inverse design approach to create a two-dimensional phononic metasurface exhibiting a highly anisotropic phonon dispersion along the main axes of the Brillouin zone. A partial hypersonic bandgap of approximately 3.5 GHz is present along one axis, with gap closure along the orthogonal axis. Such a level of control is achieved through genetically optimized unit cells, with shapes exceeding conventional intuition. We experimentally validated our theoretical predictions using Brillouin light scattering, confirming the effectiveness of the inverse design method. Our approach unlocks the potential for automated engineering of phononic metasurfaces with on-demand functionalities, thus leading toward innovative phononic devices beyond the limitations of traditional design paradigms.
PubMed: 38958360
DOI: 10.1021/acsnano.4c01954