An updated patent review of IDO1 inhibitors for cancer (2018-2022).

INTRODUCTION: Indoleamine 2,3-dioxygenase 1 (IDO1) is highly related to the immune evasion of a wide range of malignancies due to its role in the immune suppression caused by the depletion of tryptophan (Trp) and the accumulation of kynurenine (Kyn). The combination of IDO1 inhibitors with other treatments represents a promising strategy in immunotherapy, although considerable challenges lie ahead. AREAS COVERED: This review focuses on patent publications searched from Espacenet and Google Scholar, and related to IDO1 inhibitors with potential anti-cancer utilization during the period 2018-2022. EXPERT OPINION: Despite the clinical trial failure of the first-in-class IDO1 inhibitor epacadostat in combination with pembrolizumab, numerous studies have been carried on to pursue more efficient IDO1-based immune-modulating therapeutic solutions. A large number of IDO1 inhibitors with new structures and design concepts have been produced with the impetus of crystallographic studies, and have shown great research potential. The elaboration on the combination of IDO1 inhibitors with other targeting agents, the more precise selection of patients, the identification of more reliable biomarkers for evaluating the IDO1 treatment, and the investigation of possible toxicity, are critical factors to promote IDO1-based immunotherapies from bench to bedside.

Cervicogenic dizziness alleviation after coblation discoplasty: a retrospective study.

OBJECTIVE: Little is known about the therapeutic relationship between coblation discoplasty and cervicogenic dizziness (CGD). CGD can be caused by abnormal proprioceptive inputs from compressed nerve roots, intradiscal mechanoreceptors and nociceptors to the vestibulospinal nucleus in the degenerative cervical disc. The aim was to analyze the efficacy of coblation discoplasty in CGD through intradiscal nerve ablation and disc decompression in a 12-month follow-up retrospective study. METHODS: From 2015 to 2019, 42 CGD patients who received coblation discolplasty were recruited as the surgery group, and 22 CGD patients who rejected surgery were recruited as the conservative group. Using intent-to-treat (ITT) analysis, we retrospectively analyzed the CGD visual analogue scale (VAS), neck pain VAS, CGD frequency score, and the CGD alleviation rating throughout a 12-month follow-up period. RESULTS: Compared with conservative intervention, coblation discoplasty revealed a better recovery trend with effect sizes of 1.76, 2.15, 0.92, 0.78 and 0.81 in CGD VAS, and effect sizes of 1.32, 1.54, 0.93, 0.86 and 0.76in neck pain VAS at post-operative 1 week, and 1, 3, 6, 12 months, respectively. The lower CGD frequency score indicated fewer attacks of dizziness until postoperative 3 months (p < 0.01). At post-operative 12 months, the coblation procedure showed increased satisfactory outcomes of CGD alleviation rating (p < .001, -1.00 of effect size). CONCLUSIONS: Coblation discoplasty significantly improves the severity and frequency of CGD, which is important inbridging unresponsive conservative intervention and open surgery.Key messagesThere is a correlation between the degenerative cervical disc and cervicogenic dizziness (CGD).CGD can be caused by abnormal proprioceptive inputs from a compressed nerve root and intradiscal mechanoreceptors and nociceptors to the vestibulospinal nucleus in the degenerative cervical disc.Cervical coblation discoplasty can alleviate CGD through ablating intradiscal nerve endings and decompressing the nerve root.

Computed Tomography-Guided Percutaneous Coblation of the Thoracic Nerve Root for Treatment of Postherpetic Neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is one of the most intractable pain disorders and often does not respond to medication, physical, and interventional procedures. Coblation technology has been demonstrated to have potential for neuralgia, but there are rare reports of the efficacy and security of coblation for PHN. The thoracic segment is the most common predilection part of PHN, so we conducted this long-term study to investigate the results of coblation for the treatment of thoracic PHN. OBJECTIVES: The aim of this study was to determine the efficacy and security of computed tomography (CT)-guided coblation of the thoracic nerve root for treatment of PHN. STUDY DESIGN: Self before-after controlled clinical assessment. SETTING: Department of Pain Management, Xuanwu Hospital, Capital Medical University. METHODS: Seventy-seven patients with thoracic PHN sustained for at least 6 months and refractory to conservative therapy were identified. Patients underwent CT-guided percutaneous coblation to ablate the thoracic nerve root for thoracic PHN. The therapeutic effects were evaluated using a Visual Analog Scale (VAS), medication doses, and pain-related quality of life (QoL) scale before coblation, and at 1 week, and at 1, 3, and 6 months after the procedure. Patients who achieved more than 50% pain relief were defined as responders. In addition, adverse effects were also recorded to investigate the security of this procedure. RESULTS: The VAS score significantly decreased from 7.22 ± 1.15 before the coblation to 3.51 ± 1.12 (P = 0.01), 3.02 ± 1.21 (P = 0.006), 3.11 ± 2.15 (P = 0.014), and 2.98 ± 2.35 (P = 0.008) at 1 week, and at 1, 3, and 6 months after the procedure, respectively. The number of responders were 56 (77.78%), 54 (75%), 55 (76.39%), and 54 (75%) at 1 week, and at 1, 3, and 6 months after the procedure, respectively. The doses of anticonvulsants and analgesics were decreased significantly at all time points after the procedure compared with before treatment (P < 0.05). Patient responses on the Brief Pain Inventory Short Form indicated mean scores that were significantly lower than baseline across all domains of pain interference with QoL at all evaluations (P = 0.001). Most of the patients had mild numbness and it did not affect the daily activities after the procedure. No other severe adverse events occurred during or after the procedure. LIMITATIONS: A single-center study, relatively small number of patients, short duration of review of medical record, and the retrospective study. CONCLUSIONS: CT-guided percutaneous thoracic nerve root coblation is an effective and safe method for the treatment of thoracic PHN, and the procedure can also significantly improve the QoL in patients with PHN.

A20-OVA Nanoparticles Inhibit Allergic Asthma in a Murine Model.

The skewed T helper (Th) 2 response plays a critical role in the pathogenesis of allergic asthma. Regulatory T (Treg) cells and the regulatory cytokines are required in maintaining the homeostasis in the body. This study aims to determine the effects of a poly(lactic-co-glycolic) acid (PLGA)-ovalbumin (OVA)+A20 (a ubiquitin E3 ligase) nanovaccine on inhibiting allergic asthma in a murine model. In this study, A20 and OVA (a model antigen) were encapsulated into PLGA to be a nanovaccine (PLGA-OVA+A20). An allergic asthma murine model was developed with OVA as the specific antigen to test the role of PLGA-OVA+A20 nanovaccine in maintaining the immune homeostasis in the airway tissues. The results showed that PLGA-OVA+A20 nanovaccine inhibited the asthma responses in mice by suppressing Th2 inflammatory responses, promoting the generation of Treg cells in the airway tissues. We conclude that the PLGA-OVA+A20 nanovaccine has a marked inhibitory effect on the airway allergic response in sensitized mice by significantly promoting the generation of Treg cell and IL-10. The data suggest that PLGA-OVA+A20 has translational potential in the treatment of allergic asthma.

Nerve coblation for treatment of trigeminal neuralgia: A case report.

BACKGROUND: Trigeminal neuralgia (TN) is a severe type of neuropathic pain which is often inadequately managed using conventional therapies. In this report, we present the first case of TN treated with gasserian ganglion nerve coblation (NC). CASE SUMMARY: A 58-year-old man presented with right facial pain, mostly localized in the right zygomatic zone, alveolar region, and jaws. Similar to acupuncture and shock pain, the pain lasted about five seconds after each attack before resolving unaided. A diagnosis of TN was made, after which treatment with acupuncture therapy and oral carbamazepine was given. However, the pain was not satisfactorily controlled. Subsequently, gasserian ganglion NC of the right trigeminal nerve guided by computed tomography (CT) was performed on the patient. Following this procedure, the right zygomatic, alveolar, submandibular, and cheek pain disappeared completely. The right zygomatic and alveolar areas experienced mild numbness (level II). At 1-, 2-, 3-, and 6-mo follow-ups after surgery, the patient was painless and the numbness score was level I. CONCLUSION: CT-guided gasserian ganglion (NC) is an effective treatment for TN and is associated with less or no postoperative numbness or hypoesthesia in comparison with current standard-of-care approaches.

Trigeminal somatosensory-evoked potential: A neurophysiological tool to monitor the extent of lesion of ganglion radiofrequency thermocoagulation in idiopathic trigeminal neuralgia: A case-control study.

To reflect the extent of thermolesion of ganglion by testing the change of trigeminal somatosensory-evoked potential (TSEP) before and after ganglion radiofrequency thermocoagulation surgery (GRT), and evaluate long-term clinic effect by follow-up visiting of 1 year.Patients with idiopathic trigeminal neuralgia (TN) in the second division were enrolled between October 2014 and October 2015. They were treated with computed tomography-guided GRT and a follow-up visiting of 1 year. Bilateral TSEP measurements were performed 1 day before and 2 days after the GRT surgery. The latency and peak-to-peak amplitude of W2 and W3 were recorded.Immediate postprocedure pain relief (grades I-III) was 100% and 92.5% 1 year later. Facial numbness rate of grades III and IV was 70%, 40%, and 12.5%, respectively, at immediate, 2 days, and 1 year after GRT. No sever complications happened. The latency of W2 and W3 of patients who had no pain no numbness after 1 year of GRT was 1.74 ±â€Š0.24 and 3.84 ±â€Š0.66 ms, respectively, of TN side, and 1.71 ±â€Š0.39 and 3.63 ±â€Š0.85 ms of the healthy side before GRT. The amplitude of W2 and W3 was 1.13 ±â€Š0.50 and 1.99 ±â€Š1.09 uv, respectively, of TN side and 1.24 ±â€Š0.40 and 1.89 ±â€Š0.81 uv of the healthy side before GRT. There was no statistical difference of the latency and amplitude between 2 sides of W2 and W3 before surgery (P > 0.05). The latency of W2 and W3 delayed and the amplitude reduced especially in TN side after surgery comparing before (P < 0.001). And, comparisons of the latency and amplitude of W2 and W3 between TN side and the healthy side after surgery showed the latency of W2 and W3 delayed (W2: P = 0.02; W3: P = 0.01) and the amplitude of W2 reduced (P = 0.003), but the amplitude of W3 had no statistical difference (P = 0.22). The mean delayed latency and 95% confident interval of W2 and W3 were 0.22 ±â€Š0.35 (0.1-0.34) ms and 0.35 ±â€Š0.64 (0.14-0.57) ms, respectively. The mean decreased amplitude and 95% confident interval of W2 and W3 were 22 ±â€Š24 (14-30)% and 23 ±â€Š32 (12-34)%, respectively.GRT can make the latency delay and the amplitude decrease of TSEP. And the latency and amplitude of W2 and W3 can be considered reliable and safe reference for monitoring the extent of thermolesion.

Computed Tomography-Guided Percutaneously Controlled Ablation of the Thoracic Paravertebral Nerve Due to Thoracic Neuropathic Pain.

BACKGROUND: Patients with thoracic neuropathic pain often do not respond to medication and physical therapy. Coblation technology has been demonstrated to have potential for pain management. METHODS: Fifteen patients underwent computed tomography-guided percutaneous coblation to ablate the thoracic paravertebral nerve for their medication-resistant thoracic neuropathic pain. The pain intensity was assessed by visual analog scale (VAS) 1 day before surgery and 1 week and 1, 3, and 6 months after surgery, and the difference between preoperative and postoperative VAS values was determined to evaluate the pain relief effectiveness. Patients who achieved > 50% pain relief were defined as responders, and the ratio in all patients was calculated. The number of patients who reported mild pain (VAS ≤ 3) was recorded, and the ratio in all responders was calculated. In addition, adverse effects were also recorded to investigate the security of procedure. RESULTS: Twelve (80%) responders achieved > 50% pain relief. The VAS score of responders significantly decreased from 7.42 ± 1.38 before surgery to 2.17 ± 1.11 (P = 0.000), 1.92 ± 1.16 (P = 0.000), 1.75 ± 0.97 (P = 0.000), and 1.58 ± 1.08 (P = 0.000) at 1 week, 1, 3, and 6 months after surgery, respectively. The number of responders with mild pain was 10 (83.3%), 11 (91.7%), 12 (100%), and 12 (100%) at 1 week, 1, 3, and 6 months after surgery, respectively. All responders and 1 nonresponder reported slight numbness after the surgery. CONCLUSION: Percutaneous thoracic paravertebral nerve coblation guided by computed tomography is a potential method for the treatment of thoracic neuropathic pain.

Rubricella aquisinus gen. nov., sp. nov., a novel member of the family Rhodobacteraceae.

A Gram-stain negative, ovoid or short rod-shaped, aerobic and non-motile bacterial strain, designated J82T, was isolated from a seawater sample collected from the coast of Yellow Sea in Qingdao, China. The strain grew at salinities of 1.0-6.0% (w/v) NaCl (optimum, 2.5%). Growth occurred at pH 6.0-8.0 (optimum, pH 7.0) and 10-42 °C (optimum, 28-30 °C). The genomic DNA G + C content was determined to be 57.5 mol%. Q-10 was detected as the respiratory quinone. The major fatty acid (>10%) was Summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The polar lipids consisted of phosphatidylethanolamine, two unidentified aminolipids and two unidentified polar lipids. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain J82T forms a distinct evolutionary lineage within the family Rhodobacteraceae. On the basis of phenotypic, chemotaxonomic and phylogenetic characteristics, the strain merits recognition as representative of a novel genus and species within the family Rhodobacteraceae for which the name Rubricella aquisinus gen. nov., sp. nov. is proposed. The type strain of Rubricella aquisinus is J82T (= DSM 103377T = CCTCC AB 2016170T).

Clinical study of cerebrospinal fluid neuropeptides in patients with primary trigeminal neuralgia.

OBJECTIVES: To investigate the expression levels of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and ß-endorphin in the cerebrospinal fluid (CSF) and peripheral blood of patients with primary trigeminal neuralgia (TN). PATIENTS AND METHODS: We included 20 patients with primary TN who underwent percutaneous radiofrequency thermocoagulation and collected four types of samples from all of them: sample A: CSF samples; sample B: peripheral blood samples; sample C: peripheral blood samples collected one day before the operation; sample D: peripheral blood samples withdrawn one day after the operation. Another 20 CSF samples of patients with nervous system disease or gynecological disease were collected as a control (sample E). Samples A and B were obtained at the same time. We also evaluated the expression of CGRP, SP, ß-endorphin, and VIP by visual analog scale (VAS) scores one day before and one day after the operation. In addition, heart rate (HR) at baseline and at the time of sample collection, mean arterial pressure (MAP), and all side effects of the procedure were recorded. RESULTS: Significance were found concerning about CGRP, SP, ß-endorphin, and VIP in TN patients and the controls (P<0.001). The expression of CGRP, SP, and VIP in sample A was higher than that in sample E. However, the ß-endorphin level in sample A was lower than that in sample E. There was a positive correlation between sample A and B regarding the expression of CGRP, SP, ß-endorphin, and VIP (P<0. 01). There was no relationship between the time of disease onset and the expression of CGRP, SP, ß-endorphin, and VIP in sample A and sample B (P>0.05). No difference was detected between the neuropeptides levels in samples B and C (P>0.05). Notably, VAS in sample D was significantly lower than that in sample C (P<0.01). Finally, there was no difference between the intraoperative HR and MAP values in the studied samples. CONCLUSION: In primary TN patients, the blood levels of CGRP, SP, ß-endorphin, and VIP were associated with those in CSF samples. There was a significant difference between the levels of the four neuropeptides in CSF and control samples. Our results also indicated that the levels of neuropeptides in blood samples can be tested for those in CSF. The disease onset and duration exerted insignificant effects on the production and release of CGRP, SP, ß-endorphin, and VIP.

Assessment of consecutive neurolytic celiac plexus block (NCPB) technique outcomes in the management of refractory visceral cancer pain.

OBJECTIVE: The objective of this study was to assess outcomes and safety of consecutive neurolytic celiac plexus block (NCPB) technique. DESIGN: Retrospective clinical data analysis. SETTING: The study was conducted in three pain departments and academic medical center. PATIENTS: The subject of this study was 12 patients with terminal visceral (mostly pancreatic) cancer who failed conservative measures. INTERVENTIONS: Twelve celiac plexus alcohol neurolytic procedures were performed for pain control after a positive diagnostic block. MATERIALS AND METHODS: Twelve patients with terminal visceral (mostly pancreatic) cancer who failed conservative measures were managed by consecutive NCPB guided by computed tomography at the pain department of Beijing Xuanwu Hospital between January 2005 and June 2010. The present study evaluated the efficacy of consecutive NCPB technique with regard to pain relief, as well as its adverse effects and complications. RESULTS: The efficacy of consecutive NCPB technique with regard to pain relief was observed by a marked decrease in the visual analog score and in opioid consumption, with preprocedural mean values dropping from (8.7±1.0) and (155±56)mg/day of morphine to (1.8±1.1) and (0)mg/day at the first postprocedural visit, respectively. These results persisted during the 6-month follow-up period or until death. Minor adverse effects (moderate diarrhea and mild hypotension) were frequent (N=3, and N=4, respectively), and severe complications occurred in one patient with a transient paraparesis (N=1). No procedure-related mortality was observed. CONCLUSIONS: The consecutive NCPB technique can provide analgesia and the alleviation of the secondary undesirable effects of analgesic drugs resulting from the decrease of morphine consumption in patients with upper abdominal malignancies. In the subject group, the reliability of its analgesic effect is high, with lower rate of severe complications.

Continuous epidural block of the cervical vertebrae for cervicogenic headache.

BACKGROUND: Cervicogenic headache (CEH) is caused by a structural abnormality in the cervical spine. Available treatments for CEH include medical therapy, local botulinum toxin injection, cervical epidural corticosteroid injection, and surgery. The objective of this study was to investigate the safety and efficacy of a continuous epidural block of the cervical vertebra. METHODS: Medical records were retrospectively analyzed for 37 patients diagnosed with CEH treated by a continuous epidural block of the cervical vertebra with lidocaine, dexamethasone, and saline (5 ml/min) for 3 - 4 weeks and triamcinolone acetonide 5 mg once weekly for 3 - 4 weeks. Pain was measured via the visual analogue scale (VAS) in combination with quality of life assessment. Outcome measures were patient-reported days with mild or moderate pain, occurrence of severe pain, and the daily oral dosages of non-steroidal anti-inflammatory drug use (NSAID). RESULTS: In the 3 months immediately preceding placement of the epidural catheter, the mean number of days with mild or moderate pain was 22.0 +/- 4.3. The mean occurrence of severe pain was (3.20 +/- 0.75) times and the mean oral dosage of NSAID was (1267 +/- 325) mg. During the first 6 months after epidural administration of lidocaine and corticosteroids, the mean number of days with mild or moderate pain, the mean occurrence of severe pain, and the mean daily oral dosages of NSAIDs were significantly decreased compared to 3-month period immediately preceding treatment (P < 0.01). By 12 months post-treatment, no significant difference in these three outcome measures was noted. CONCLUSIONS: Continuous epidural block of the cervical vertebra for patients with CEH is effective for at least six months. Further research is needed to elucidate mechanisms of action and to prolong this effect.

Effect of neurolytic celiac plexus block guided by computerized tomography on pancreatic cancer pain.

The efficacy of neurolytic coeliac plexus block (NCPB) guided by computerized tomography (CT) was compared with pharmacological therapy in the treatment of pain due to pancreatic cancer. The study involved 56 patients who were placed randomly in either a NCPB group and pharmacological therapy group. At day 1, 7, and 14, the visual analogue scale (VAS) pain scores of the NCPB group were significantly lower than those of the pharmacological therapy group (P < 0.01), with values of 1.3 +/- 0.8 versus 4.1 +/- 0.9, 1.7 +/- 1.1 versus 3.1 +/- 1.1, and 2.0 +/- 1.1 versus 2.9 +/- 0.6, respectively. However, the differences in the improvement of quality of life (QOL) between two groups were not statistically significant. Moreover, the dose of opioid was significantly lower in the patients of group 1 than those of group 2, while the complications related to NCPB were transient. We therefore concludes that CT-guided NCPB with alcohol is an effective and safe modality in the management of intractable pancreatic cancer pain.