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1.
Soft Matter ; 20(16): 3458-3463, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38567457

ABSTRACT

We studied circular papers impregnated with camphor (CPs) and CPs with magnets (MCPs) as self-propelled objects floating on water under the compression of the water surface as an inanimate system for evacuation in an emergency. Two water chambers-Cin and Cout-were connected via a plastic gate, and eight CPs or eight MCPs were placed on Cin. We monitored the movement of the CPs or MCPs from Cin to Cout when the gate was opened and the area of Cin (Ain) was decreased using a barrier. When Ain was large, CPs moved stochastically from Cin to Cout while exhibiting random motion. The escape probability from Cin to Cout (P) at time t = 20 s increased with a decrease in Ain, and the rate of increase in P increased depending on the width of the gate (Wg). By contrast, clustering was observed for MCPs. Consequently, P of MCPs was lower than that of CPs. The difference in the surface tension between Cin and Cout (Δγ) increased with a decrease in Ain. P is discussed in relation to Δγ as the driving force for emergencies and the repulsive forces between CPs or attractive forces between MCPs. These results suggest that the repulsive force enhances the self-propulsion of objects towards the gate, that is, as a result, higher values of P are obtained.

2.
World Neurosurg ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38548056

ABSTRACT

OBJECTIVE: Glioma and meningioma require vastly different surgical approaches, even if only involving a simple craniotomy procedure. Diffusion weighted imaging (DWI) is useful for the postoperative evaluation of ischemic damage. The present study evaluated the expected but unproven differences in DWI findings. METHODS: A total of 41 patients with meningiomas and 63 with gliomas met the inclusion criteria for adult cases with superficial lesions treated through simple supratentorial craniotomy. Postoperative DWI findings of DWI-positive rate, DWI-positive area type, and relationship with neurological deficits were evaluated. RESULTS: The DWI-positive rate (P = 0.01) and the proportion of rim-type lesions (P < 0.01) were significantly more common in gliomas. Patients with meningiomas and DWI-positive areas presented with higher rates of new neurological deficits (P < 0.01), and patients with meningiomas on the left side were more likely to develop new neurological deficits (P = 0.02). Patients with gliomas tended to develop new deficits with larger DWI-positive area volumes (P = 0.04). CONCLUSIONS: Postoperative early DWI-positive rate and rim-type lesions are more common after glioma resection than meningioma resection. Larger volumes of DWI-positive areas may be associated with postoperative neurological symptoms in gliomas. DWI-positive finding is less common after meningioma than glioma resection but more likely to be associated with new neurological symptoms. These differences are important for adequate postoperative DWI evaluation of common supratentorial brain tumors.

3.
Langmuir ; 40(13): 6878-6883, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38501274

ABSTRACT

Certain odors have been shown not only to cause health problems and stress but also to affect skin barrier function. Therefore, it is important to understand olfactory masking to develop effective fragrances to mask malodors. However, olfaction and olfactory masking mechanisms are not yet fully understood. To understand the mechanism of the masking effect that has been studied, the responses of several target substance (TS) molecules-1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) mixed molecular layers to odorant (OD) molecules were examined as a simple experimental model of epithelial cellular membranes injured by TS molecules. Here, we examined trans-2-nonenal, 1-nonanal, trans-2-decenal, and 1-decanal as TS molecules to clarify the effects of double bonds and hydrocarbon chain lengths on the phospholipid molecular layer. In addition, benzaldehyde and cyclohexanecarboxaldehyde were utilized as OD molecules to clarify the masking effect of the aromatic ring. Surface pressure (Π)-area (A) isotherms were measured to clarify the adsorption or desorption of TS and OD molecules on the DOPC molecular layer. In addition, Fourier transform infrared spectroscopy was performed to clarify the interactions among DOPC, TS, and OD molecules. We found that TS molecules with and without double bonds had different effects on the DOPC molecular layer and that molecules with shorter chain lengths had greater effects on the DOPC molecular layer. Furthermore, OD molecules with aromatic rings counteracted the effects of the TS molecules. On the basis of this research, not only a detailed mechanism by which odor molecules affect lipid membranes without mediating olfactory receptors is elucidated but also more effective OD molecules with masking effects are proposed.


Subject(s)
Lipid Bilayers , Phosphatidylcholines , Molecular Structure , Lipid Bilayers/chemistry , Phosphatidylcholines/chemistry , Phospholipids/chemistry , Glycerylphosphorylcholine
4.
J Colloid Interface Sci ; 663: 329-335, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38402826

ABSTRACT

A benzoic acid (BA) disk was investigated as a novel self-propelled object whose driving force was the difference in surface tension. 4-Stearoyl amidobenzoic acid (SABA) was synthesized as an amphiphile to control the nature of motion based on intermolecular interactions between BA and SABA. The BA disk exhibited characteristic motion depending on the surface density of the SABA on the aqueous phase, that is, reciprocating motion as a one-dimensional motion and restricted and unrestricted motion as a two-dimensional motion. The trajectory of the reciprocating motion was determined by the initial direction of motion, and the boundary between an aqueous surface and the BA-SABA condensed molecular layer was used as the field's boundary. The presented results indicate that the characteristic nature of motion can be designed at the molecular level based on the intermolecular interactions between an energy-source molecule and an amphiphile.

5.
Phys Chem Chem Phys ; 26(10): 8488-8493, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38411193

ABSTRACT

We studied the self-propulsion of a camphor disk floating on a water surface using two types of ionic liquids (hexylammonium-trifluoroacetate (HHexam-TFA) and hexylethylenediaminium-trifluoroacetate (HHexen-TFA)). Bifurcation between continuous, oscillatory, and no motion was observed depending on the concentration of the ionic liquid. The bifurcation concentration between oscillatory and no motion for HHexam-TFA was lower than that for HHexen-TFA. The different bifurcation concentrations are discussed in relation to the surface tension and Fourier transform infrared spectra of the mixtures of camphor and ionic liquids. These results suggest that the interaction between the ionic liquid molecules at the air/water interface is weakened by the addition of camphor molecules and the features of self-propulsion vary due to the change in the driving force.

6.
Jpn J Nurs Sci ; 21(1): e12561, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37727042

ABSTRACT

AIM: This study clarifies the physical, psychological, and social forms of distress in, and care needs of, cardiac surgery patients, including optimal times for supporting them in their post-hospital discharge daily lives. METHODS: Semi-structured qualitative interviews were conducted. Participants included 12 adults (11 male and one female, mean age = 66.5 years) who had undergone cardiac surgery, experienced intensive care, and received outpatient care at the first post-discharge visit (around 2 ~ 3 weeks after discharge), around 3 months after discharge, and between 3 months and 1 year after discharge. Verbatim transcripts were analyzed based on similarities and differences for codes based on assessment items, and subcategories and categories were generated. RESULTS: After surgery, patients experienced physical, psychological, and social distress. First, they experienced physical pain shortly after discharge. Moreover, as they recovered at home, a gap between their sense of their recovery and the perceptions of those around them about their recovery often persisted, which led to psychological and social distress. Patients gained a sense of safety through "assurance of physical recovery" and security through "shared subjective distress." CONCLUSIONS: Post-cardiac surgery patients seek reassurance and safety by sharing experiences owing to daily life distress. Our findings could help provide better support to meet the care needs of such patients.


Subject(s)
Cardiac Surgical Procedures , Patient Discharge , Adult , Humans , Male , Female , Aged , Aftercare , Pain , Critical Care , Qualitative Research
8.
ACS Sens ; 8(12): 4494-4503, 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-38060767

ABSTRACT

We propose a novel odor-sensing system based on the dynamic response of phospholipid molecular layers for artificial olfaction. Organisms obtain information about their surroundings based on multidimensional information obtained from sniffing, i.e., periodic perturbations. Semiconductor- and receptor-based odor sensors have been developed previously. However, these sensors predominantly identify odors based on one-dimensional information, which limits the type of odor molecule they can identify. Therefore, the development of odor sensors that mimic the olfactory systems of living organisms is useful to overcome this limitation. In this study, we developed a novel odor-sensing system based on the dynamics of phospholipids that responds delicately to chemical substances at room temperature using multidimensional information obtained from periodic perturbations. Odor molecules are periodically supplied to the phospholipid molecular layer as an input sample. The waveform of the surface tension of the phospholipid molecular layer changes depending on the odor molecules and serves as an output. Such characteristic responses originating from the dynamics of odor molecules on the phospholipid molecular layer can be reproduced numerically. The phospholipid molecular layer amplified the information originating from the odor molecule, and the mechanism was evaluated by using surface pressure-area isotherms. This paper offers a platform for an interface-chemistry-based artificial sniffing system as an active sensor and a novel olfactory mechanism via physicochemical responses of the receptor-independent membranes of the organism.


Subject(s)
Odorants , Smell , Smell/physiology
9.
J Phys Chem Lett ; 14(41): 9279-9284, 2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37815116

ABSTRACT

An organic droplet containing thymol acetate (TA) floating on a sodium dodecyl sulfate aqueous phase was examined to develop a novel self-propelled object based on reaction kinetics. Two types of oscillatory motion, without back-and-forth motion (Osc I) and with back-and-forth motion (Osc II), were observed by varying the pH of the aqueous phase. The oscillation frequency reached its maximum at pH 9.6, coinciding with the occurrence of Osc II. The kinetics of the hydrolysis of TA as a reactant and the acid-base equilibrium between thymol (TOH) and the thymolate ion (TO-) as products were evaluated experimentally. The driving force of motion was discussed on the basis of the interfacial tension. The pH dependence of the oscillation frequency and the selection of Osc I or II were attributed to the equilibrium between the TOH and TO-. These results highlight the possibility of designing self-propulsion systems by considering reaction kinetics and chemical properties.

10.
Phys Chem Chem Phys ; 25(20): 14546-14551, 2023 May 24.
Article in English | MEDLINE | ID: mdl-37191103

ABSTRACT

We have developed a self-propelled object, which is composed of a plastic cup and a camphor disk, on water to reflect its three-dimensional shape in the nature of motion. The self-propelled object, of which the driving force of motion is the difference in the surface tension, exhibited oscillatory motion between motion and rest. The period and the maximum speed of oscillatory motion increased and decreased depending on the height of the cup, h, respectively. Two types of diffusion coefficients were estimated based on the diffusion of camphor molecules which were indirectly visualized using 7-hydroxycoumarin. The experimental result on the period of oscillatory motion depending on h could be reproduced by the numerical calculation based on the diffusion of camphor molecules around the object and the diffusion coefficients which were experimentally estimated. The experimental results suggest that characteristic features of motion can be created based on the three-dimensional shape of the object.

11.
Phys Chem Chem Phys ; 25(18): 12974-12978, 2023 May 10.
Article in English | MEDLINE | ID: mdl-37099288

ABSTRACT

Chemical gardens formed from two metal salts (MCl2 or MSO4) have been investigated to understand the effects of mixing on the growth of precipitate tubes. The growth of tubes can be classified into three types, i.e., collaborative, inhibited, and individual growth, depending on the combination of the two metal salts. Characteristic features of tube growth are discussed in relation to the flow near the tip of the tube controlled by osmotic pressure and the solubility product, Ksp, for M(OH)2. The present study can be interpreted as an inanimate model system of symbiosis among different species, such as mixed cropping systems and survival among different kinds of microbial cells.

12.
J Colloid Interface Sci ; 639: 324-332, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36805757

ABSTRACT

Reconstructing recursive chemotaxis in inanimate self-propelled objects is inevitable in the development of recursively and autonomously artificial mass transport systems. However, the fabrication of inanimately recursive chemotaxis has been extremely challenging because of the difficulty in introducing competitive positive and negative feedback into an inanimate self-propelled object. Herein, a coumarin derivative (coumarin, 4-methylcoumarin (4-MC), or 6-methylcoumarin (6-MC))-based disk floated on water as a self-propelled object exhibited characteristic features of motion; these features include continuous motion, repetition between positive and negative chemotaxis to the Na3PO4 powder as a base stimulus, and oscillatory motion above the Na3PO4 powder depending on the Na3PO4 density of the powder and the functional group of coumarin derivatives. The mechanism of the characteristic features of motion to the base stimulus is discussed in relation to the surface tension of the coumarin derivatives as the driving force of motion and the reaction rate of the hydrolysis between coumarin derivatives and OH- obtained from Na3PO4. This study suggests a novel avenue for developing a recursive chemotactic system coupled with reaction kinetics in self-organized motion.

13.
Langmuir ; 39(5): 2073-2079, 2023 Feb 07.
Article in English | MEDLINE | ID: mdl-36692295

ABSTRACT

Subsequent synthesis and detection using droplets as microreactors have shown promise in the development of novel materials and drugs because microreactors enable small-scale synthesis and detection of covalent/non-covalent intermolecular interactions. Self-organization exhibited by autonomous droplets under non-equilibrium conditions is beneficial for manipulating the sequentiality and selectivity of droplet coalescence because expensive equipment or elaborate techniques are not required with the autonomy of droplets. However, to our knowledge, selective coalescence caused by the collective motion of self-propelled droplets has not been demonstrated in inanimate systems. Here, we report sequentially selective coalescence based on the dynamic collective pattern of self-propelled droplets composed of ethyl salicylate (ES) or butyl salicylate (BS). When ES and BS droplets were placed on an aqueous sodium dodecyl sulfate (SDS) solution, the collective motion of droplets resulted in three stages of selective coalescence on the time development. Initially, coalescence was observed only between different types of self-propelled droplets. Subsequently, the formed droplets selectively coalesced with ES droplets. Finally, mature droplets merged with BS droplets. The sequentially selective coalescence was discussed from the dynamic pattern formation of swarming droplets and the collapse of the SDS monolayer at the o/w interface caused by the difference in Laplace pressure and the interfacial instability at the contact point between droplets. Thus, this study formulates a strategy of sequentially selective coalescence of droplets via the collective motion of non-identical self-propelled droplets, promoting a new type of powerful and efficient automation technology based on an autonomous inanimate manner of spatiotemporal pattern formation under non-equilibrium conditions for the droplet manipulation.

14.
Acta Neurol Belg ; 123(1): 161-171, 2023 Feb.
Article in English | MEDLINE | ID: mdl-34426955

ABSTRACT

BACKGROUND: Surgical evacuation of intracranial hematoma, including epidural, subdural, intracerebral, and intraventricular hematoma, is recommended in patients with traumatic brain injury (TBI) for prevention of cerebral herniation and possible saving of life. However, preoperative coagulopathy is a major concern for emergent surgery on patients with severe TBI. METHODS: We reviewed 65 consecutive patients with severe TBI who underwent emergency craniotomy for intracranial hematomas. RESULTS: Univariate analysis showed preoperative pupil abnormality, absence of pupil light reflex, respiratory failure, preoperative thrombocytopenia (< 100 × 109/L), increased activated partial thromboplastin time (> 36 s), low fibrinogen (< 150 mg/dL), platelet transfusion, red cell concentrate transfusion, and presence of brain contusion and traumatic subarachnoid hemorrhage (SAH) on computed tomography were correlated with poor outcome (death or vegetative state). Multivariate analysis revealed that pupil abnormality (p = 0.001; odds ratio [OR] 0.064, 95% confidence interval [CI] 0.012-0.344), preoperative thrombocytopenia (p = 0.016; OR 0.101, 95% CI 0.016-0.656), and traumatic SAH (p = 0.021; OR 0.211, 95% CI 0.057-0.791) were significant factors. Investigation of the 14 patients with preoperative thrombocytopenia found the emergency surgery was successful, with no postoperative bleeding during hospitalization. However, half of the patients died, and almost a quarter remained in the vegetative state mainly associated with severe cerebral edema. CONCLUSIONS: Emergent craniotomy for patients with severe TBI who have preoperative thrombocytopenia is often successful, but the prognosis is often poor. Emergency medical care teams and neurosurgeons should be aware of this discrepancy between successful surgery and poor prognosis in these patients. Further study may be needed on the cerebral edema regulator function of platelets.


Subject(s)
Anemia , Brain Edema , Brain Injuries, Traumatic , Intracranial Hemorrhage, Traumatic , Thrombocytopenia , Humans , Persistent Vegetative State/complications , Intracranial Hemorrhage, Traumatic/complications , Intracranial Hemorrhage, Traumatic/diagnostic imaging , Intracranial Hemorrhage, Traumatic/surgery , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/diagnostic imaging , Brain Injuries, Traumatic/surgery , Thrombocytopenia/complications , Craniotomy/adverse effects , Anemia/complications , Hematoma/etiology , Retrospective Studies
15.
Neuro Oncol ; 25(5): 899-912, 2023 05 04.
Article in English | MEDLINE | ID: mdl-36273330

ABSTRACT

BACKGROUND: Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. METHODS: SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. RESULTS: High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. CONCLUSIONS: High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.


Subject(s)
Cerebellar Neoplasms , Medulloblastoma , Humans , Medulloblastoma/drug therapy , Medulloblastoma/genetics , Cisplatin/pharmacology , Up-Regulation , Irinotecan , Cerebellar Neoplasms/drug therapy , Cerebellar Neoplasms/genetics , Epigenesis, Genetic , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Nuclear Proteins/metabolism
17.
Virchows Arch ; 481(6): 913-923, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36056239

ABSTRACT

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that can occur at any location. Since the identification of specific NAB2-STAT6 fusion in SFTs, the fusion gene variants, NAB2 exon 4-STAT6 exon 2/3 and NAB2 exon 5/6/7-STAT6 exon 16/17/18, have been reported to be associated with clinicopathological features, and the latter variant is predominant in meningeal SFTs. SFTs developing in the salivary glands are rare, and more rarely, those involving ectopic salivary glands (ESGs) have been reported in the cerebellopontine angle (CPA); however, their characteristics remain not well understood. In this study, we performed a clinicopathological and molecular analysis of 3 cases of meningeal SFT with ESGs. All cases presented with an extra-axial mass in the CPA, which is a rarer location for intracranial ESGs compared to the sellar region. Histologically, except for the presence of ESGs, there was no significant difference between current cases and ordinary SFTs. The ESGs demonstrated no cellular atypia, and although the spindle tumor cells were immunopositive for STAT6, the ESGs were negative in all cases, supporting that the ESGs are non-neoplastic components. In 1 case, ESGs were found only in the primary tumor and disappeared in recurrence/dissemination. Of note, molecular analysis identified NAB2 exon 4-STAT6 exon 2 in all cases. In conclusion, our results suggest that ESGs particularly in the CPA may be associated with SFTs and that meningeal SFTs with ESGs may be associated with the minor fusion variant of NAB2-STAT6 in the intracranial lesions.


Subject(s)
Meningeal Neoplasms , Soft Tissue Neoplasms , Solitary Fibrous Tumors , Humans , Cerebellopontine Angle/metabolism , Cerebellopontine Angle/pathology , Oncogene Proteins, Fusion/genetics , Repressor Proteins/genetics , Repressor Proteins/metabolism , Solitary Fibrous Tumors/genetics , Solitary Fibrous Tumors/pathology , STAT6 Transcription Factor/genetics , Meningeal Neoplasms/genetics , Salivary Glands/metabolism , Biomarkers, Tumor/genetics , Gene Fusion
18.
World Neurosurg ; 167: e27-e39, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35948227

ABSTRACT

OBJECTIVE: Differentiation of suprasellar xanthogranuloma (XG) from adult craniopharyngioma (CP) can be problematic in endoscopic extended transsphenoidal surgery. METHODS: We reviewed the clinical data, preoperative imaging, intraoperative endoscopic findings, and intraoperative frozen section pathology in newly diagnosed adult CPs (19 patients) and XGs (6 patients). RESULTS: Intracystic signal intensity was often high on T1-weighted magnetic resonance images in the XGs but low in the CPs (P = 0.015). Capsular intensity was low on T2-weighted imaging in XGs but iso to high in CPs (P < 0.001). Capsular gadolinium enhancement was often seen in CPs and not in XGs (P < 0.001). CPs often had a solid component with contrast enhancement but none in XGs (P < 0.001). Intraoperative endoscopic observations frequently found a whitish solid component in the CPs but yellow to brown fibrous granulomatous lesions in XGs (P < 0.001). The tumor capsule was dark grayish and soft in CPs, whereas it was fibrously hard in XGs (P = 0.002). Yellowish hemosiderin deposits were seen in all XGs (P = 0.003). Intraoperative pathologic diagnosis of CP was all verified whereas no evidence of tumor was found in XGs (P < 0.001). Partial removal was performed in 4 patients with XGs. No recurrence was observed in these patients during the follow-up period (1.5-8 years). CONCLUSIONS: Careful interpretation of preoperative magnetic resonance imaging, intraoperative endoscopic findings, and intraoperative frozen section diagnosis may be important for the differential diagnosis between XG and CP. In endoscopic-extended transsphenoidal surgery, intentional partial removal can be effective for XG after careful diagnosis.


Subject(s)
Craniopharyngioma , Pituitary Neoplasms , Soft Tissue Neoplasms , Adult , Humans , Contrast Media , Craniopharyngioma/diagnostic imaging , Craniopharyngioma/surgery , Craniopharyngioma/pathology , Endoscopy/methods , Gadolinium , Granuloma/diagnostic imaging , Granuloma/surgery , Magnetic Resonance Imaging , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/surgery , Pituitary Neoplasms/pathology
19.
Chaos ; 32(7): 073103, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35907716

ABSTRACT

The Belousov-Zhabotinsky (BZ) reaction was investigated to elucidate features of oscillations depending on the applied electrical potential, E. A cation-exchange resin bead loaded with the catalyst of the BZ reaction was placed on a platinum plate as a working electrode and then E was applied. We found that global oscillations (GO) and a reduced state coexisted on the bead at a negative value of E and that the source point of GO changed depending on E. The thickness of the reduced state was determined by a yellow colored region which corresponded to the distribution of Br2. The present studies suggest that the distribution of the inhibitor, Br-, which is produced from Br2, plays an important role in the existence of the reduced state and GO, and the source point of GO.


Subject(s)
Electricity , Catalysis
20.
Digestion ; 103(5): 329-338, 2022.
Article in English | MEDLINE | ID: mdl-35697000

ABSTRACT

BACKGROUND AND AIMS: A considerable number of patients with ulcerative colitis (UC) who initially respond to golimumab (GLM), an anti-TNF-α antibody, gradually lose clinical response. Therapeutic drug monitoring has been proposed to optimize serum anti-TNF-α antibody concentrations before the loss of response; however, little is known about ideal serum GLM concentrations. We aimed to evaluate whether the serum GLM trough levels (TLs) early after the initiation of induction therapy affect the long-term outcomes in UC and to identify the early GLM TLs that should be targeted for better long-term outcomes. METHODS: Thirty-one patients were prospectively evaluated. The primary outcome was clinical remission at 54 weeks, and we measured the serum GLM TLs at weeks 6, 10, and 14. Receiver operating characteristic (ROC) curves were constructed to identify optimal GLM TL thresholds early after induction therapy that were associated with clinical remission at week 54. RESULTS: The GLM TL at week 14, but not at weeks 6 or 10, was significantly associated with clinical remission at week 54 (median [IQR] 1.6 [1.3-1.6] µg/mL vs. 0.9 [0.6-1.3] µg/mL; p = 0.04). The area under the ROC curve for GLM TLs at week 14 was 0.78. We identified a week-14 GLM TL of 1.1 µg/mL as the target threshold for achieving clinical remission at week 54. CONCLUSION: Our results demonstrate the value of early serum GLM TLs in predicting the long-term outcomes of GLM for patients with UC.


Subject(s)
Colitis, Ulcerative , Antibodies, Monoclonal , Drug Monitoring , Humans , Remission Induction , Treatment Outcome , Tumor Necrosis Factor Inhibitors , Tumor Necrosis Factor-alpha
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