Association between hospital palliative care team intervention volume and patient outcomes.

BACKGROUND: The benefits of palliative care in patients with advanced cancer are well established. However, the effect of the skills of the palliative care team (PCT) on patient outcomes remains unclear. Our aim was to evaluate the association between hospital PCT intervention volume and patient outcomes in patients with cancer. METHODS: A retrospective cohort study was conducted using a nationwide inpatient database in Japan. Patients with cancer receiving chemotherapy and PCT intervention from 2015 to 2020 were included. The outcomes were incidence of hyperactive delirium within 30 days of admission, mortality within 30 days of admission, and decline in activities of daily living (ADL) at discharge. The exposure of interest was hospital PCT intervention volume (annual number of new PCT interventions in a hospital), which was categorized into low-, intermediate-, and high-volume groups according to tertiles. Multivariate logistic regression and restricted cubic-spline regression were conducted. RESULTS: Of 29,076 patients, 1495 (5.1%), 562 (1.9%), and 3026 (10.4%) developed delirium, mortality, and decline in ADL, respectively. Compared with the low hospital PCT intervention volume group (1-103 cases/year, n = 9712), the intermediate (104-195, n = 9664) and high (196-679, n = 9700) volume groups showed significant association with lower odds ratios of 30-day delirium (odds ratio, 0.79 [95% confidence interval, 0.69-0.91] and 0.80 [0.69-0.93], respectively), 30-day mortality (0.73 [0.60-0.90] and 0.59 [0.46-0.75], respectively), and decline in ADL (0.77 [0.70-0.84] and 0.52 [0.47-0.58], respectively). CONCLUSION: Hospital PCT intervention volume is inversely associated with the odds ratios of delirium, mortality, and decline in ADL among hospitalized patients with cancer.

Effect of pentavalent inorganic arsenic salt on erythropoietin production and autophagy induction.

Arsenic is abundant in the environment and takes the form of trivalent and pentavalent arsenic compounds. Arsenite has been reported to both promote and suppress erythropoietin (EPO) production and autophagy induction. EPO production is involved in hematopoiesis, and autophagy induction is involved in cytoprotection, both of which are thought to be cellular responses to arsenic stress. While there are reports that show the effects of EPO on autophagy induction, the relationship between EPO production and autophagy induction is unclear. Therefore, this study analyzed the effect of the pentavalent inorganic arsenic salt arsenate on EPO production in vitro and in vivo and EPO-induced autophagy in HepG2 cells. Exposure of HepG2 cells to low-concentration arsenate was observed to increase EPO production and induced autophagy. Moreover, a ROS scavenger suppressed the arsenate-induced increase in autophagy and EPO mRNA levels. Both EPO production and autophagy induction contributed to protection from arsenate-induced cytotoxic stress. HepG2 cells expressed the EPO receptor and production of EPO by HepG2 cells acted in an autoregulatory manner to suppress autophagy induction. In vivo administration of low-concentration arsenate to rats increased EPO mRNA levels in the liver and kidney. These results suggested that low-concentration arsenate promotes EPO production and autophagy induction in HepG2 cells, and the resultant EPO production contributes to cytoprotection of cultured cells via EPO receptor activation.

Gabapentinoid Use Is Associated With Reduced Occurrence of Hyperactive Delirium in Older Cancer Patients Undergoing Chemotherapy: A Nationwide Retrospective Cohort Study in Japan.

BACKGROUND: It is unclear whether gabapentinoids affect the development of delirium. We aimed to determine the association between gabapentinoid use and hyperactive delirium in older cancer patients undergoing chemotherapy. METHODS: We conducted propensity score-matched analyses using data from a nationwide inpatient database in Japan. We included cancer patients with pain ≥70 years of age undergoing chemotherapy between April 2016 and March 2018. Patients receiving gabapentinoids were matched with control patients using propensity scores. The primary outcome was occurrence of hyperactive delirium during hospitalization, and the secondary outcomes were length of hospital stay, in-hospital fractures, and in-hospital mortality. Hyperactive delirium was identified by antipsychotic use or discharge diagnoses from the International Classification of Diseases, 10th Revision. RESULTS: Among 143,132 identified patients (59% men; mean age, 76.3 years), 14,174 (9.9%) received gabapentinoids and 128,958 (90.1%) did not (control group). After one-to-one propensity score matching, 14,173 patients were included in each group. The occurrence of hyperactive delirium was significantly lower (5.2% vs 8.5%; difference in percent, -3.2% [95% confidence interval, -3.8 to -2.6]; odds ratio, 0.60 [0.54-0.66]; P < .001), the median length of hospital stay was significantly shorter (6 days [interquartile range, 3-15] vs 9 days [4-17]; subdistribution hazard ratio, 1.22 [1.19-1.25]; P < .001), and the occurrence of in-hospital mortality was significantly lower in the gabapentinoid group than in the control group (1.3% vs 1.8%; difference in percent, -0.6% [-0.9 to -0.3]; odds ratio, 0.69 [0.57-0.83]; P < .001). Gabapentinoid use was not significantly associated with the occurrence of in-hospital fractures (0.2% vs 0.2%; difference in percent, 0.0% [-0.1 to 0.1]; odds ratio, 1.07 [0.65-1.76]; P = .799). The results of sensitivity analyses using stabilized inverse probability of treatment weighting were consistent with the results of the propensity score-matched analyses. CONCLUSIONS: Our findings suggest that gabapentinoid use is associated with reduced hyperactive delirium in older cancer patients undergoing chemotherapy, with no evidence of an increase in the fracture rate, length of hospital stay, or in-hospital death.

A Novel Technique Using Magnetic Resonance Imaging in the Supine and Prone Positions for Diagnosing Lumbar Adhesive Arachnoiditis: A Preliminary Study.

BACKGROUND: Lumbar adhesive arachnoiditis is a debilitating neuropathic condition and is difficult to diagnose owing to lack of definitive diagnostic criteria. By focusing on the intrathecal mobility of nerve roots, we assessed whether useful diagnostic criteria could be established using MRI. METHODS: Seventeen patients with a high risk for lumbar adhesive arachnoiditis and 18 no-risk patients with chronic low back pain and/or leg pain participated in this study. The patients underwent MRI in both the supine and prone positions. Eleven axial T2-weighted images between the L2 and L5/S levels were obtained, and the proportion of the low-intensity area in the dorsal half to the total low-intensity area in the dural sac was calculated for each axial view. RESULTS: At some lumbar levels, the low-intensity area in the dorsal half of the dural sac was relatively larger in patients with a high risk for lumbar adhesive arachnoiditis than in the no-risk patients. In the no-risk group, the proportion of the low-intensity area in the dorsal half in the supine position was significantly higher than that in the prone position at all lumbar levels. However, in the high-risk group, at some levels, the proportions were not significantly different in the dorsal half of the dural sac between the supine and prone positions. CONCLUSION: In patients with a known risk for lumbar adhesive arachnoiditis, nerve roots lose their potential to migrate in the dural sac in the gravitational force direction on MRI.

Development of the Japanese Version of the Leeds Assessment of the Neuropathic Symptoms and Signs Pain Scale: Diagnostic Utility in a Clinical Setting.

OBJECTIVE: We aimed to assess the diagnostic utility of the linguistically validated Japanese version of the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS-J) as a screening tool for neuropathic pain in the clinical setting. METHODS: Patients with neuropathic pain or nociceptive pain who were 20 to 85 years of age were included. Sensitivity and specificity using the original cutoff value of 12 were assessed to evaluate the diagnostic utility of the LANSS-J. Sensitivity and specificity with possible cutoff values were calculated, along with area under the receiver operating characteristic curve. We then evaluated agreement regarding assessment of the LANSS-J by two investigators. We used the intraclass correlation coefficient (ICC) for the total score and Cohen's kappa coefficient for each item. RESULTS: Data for patients with neuropathic pain (n = 30) and those with nociceptive pain (n = 29) were analyzed. With a cutoff of 12, the sensitivity was 63.3% (19/30) and the specificity 93.1% (27/29). Sensitivity improved substantially with a cutoff of ≤ 11 (≥ 83.3%, 25/30). High specificity (93.1%, 27/29) was sustained with a cutoff of 9 to 12. The ICC for the total score was 0.85, indicating sufficient agreement. Kappa coefficients ranged from 0.68 to 0.84. CONCLUSIONS: The LANSS-J is a valid screening tool for detecting neuropathic pain. Our results suggest that employing the original cutoff value provides high specificity, although a lower cutoff value of 10 or 11 (with its high specificity maintained) may be more beneficial when pain attributed to neuropathic mechanisms is suspected in Japanese patients.

[Understanding Opioid-induced Adverse Effects and its Managements].

Opioids are potent analgesics and improve both noci- ceptive and neuropathic pain. However, some patients suffer opioid-induced adverse effects, including not only somnolence, nausea and vomiting, and constipation (bowel dysfunction) but also osteoporosis, immunode- ficiency, paradoxical hyperalgesia and addiction. These adverse effects could derive from stimulating opioid receptors either in the central nervous system or at the periphery. Here, we explain the mechanisms of opioid-induced adverse effects and respective manage- ments of them. To control opioid-induced constipation, the peripheral-acting mu-opioid receptor antagonists (PAMORAs) have been widely used in USA. We dis- cuss features of and expectations for PAMORAs in Japan. Further, to avoid developing opioid addiction, we introduce the concept of 'Health literacy' and the measuring tool 'Newest Vital Sign Japanese version'. Controlling pain by opioids adequately and preventing and managing opioid-induced adverse effects ade- quately can result in improvement of QOL of patients with chronic pain.

[A Case of Epidural Hematoma Associated with Epidural Anesthesia].

We report a case of epidural hematoma in an elderly patient with normal coagulability and without difficulty in epidural catheterization. A 76-year-old man with a history of cervical myelopathy was scheduled for gastrojejunostomy under combined epidural and general anesthesia. He had normal bleeding time, coagulation test results, and platelet count. He underwent an epidural catheterization without difficulty. On the first postoperative day, he noticed that could not move his legs with analgesia. After stopping continuous epidural perfusion, he could move legs slightly, but paraplegia remained. On the second postoperative day, MRI of the spine demonstrated a hematoma-like lesion, and severe thoracic and lumbar spinal canal stenosis. Severe vertebral deformation, especially in cases of the elderly, is a potential risk for epidural hematoma after epidural catheterization, because a small hematoma may compress the spinal cord. A careful preoperative evaluation whether to perform epidural catheterization and postoperative observation are required for elderly patients with severe vertebral deformation.

Effects of preoperatively administered carbamazepine and phenytoin on rocuronium-induced neuromuscular block under sevoflurane anesthesia: a retrospective clinical study.

We examined the effects of preoperatively administered phenytoin and carbamazepine on rocuronium-induced neuromuscular block under sevoflurane anesthesia in this retrospective clinical study. When compared to patients without anticonvulsant therapy (n = 16), the recovery index (i.e., the time required from 25% of spontaneous return of T1 to 75% of spontaneous return of T1) was significantly lower in patients with anticonvulsant therapy using carbamazepine and/ or phenytoin (n = 17); however, no significant dose-dependent effects of carbamazepine as well as phenytoin on the recovery index were detected. Further studies are required to elucidate the mechanisms underlying the modifying effects of carbamazepine and phenytoin on pharmacokinetics and pharmacodynamics of rocuronium.

Allergic reactions to propofol in adult patients with egg or soybean allergy: a retrospective cohort study from a large database of a single institute.

BACKGROUND: In recent years, many reports have indicated that propofol is safe to administer to patients with egg/soybean allergy in Western countries. Egg allergy is more frequent in Asia, but there are limited reports regarding allergic reactions to propofol use among adults. This study aimed to determine whether propofol causes allergic reactions in patients with egg/soybean allergy. METHODS: Adult patients who underwent surgery involving anesthesiologists from 2018 to 2021 were included. In all patients, we reviewed food allergy information in their electronic medical record and extracted anesthetics. Patients with egg/soybean allergy were subdivided into two groups on the basis of intraoperative use of propofol. We evaluated each group for allergic reactions within 24 h after the induction of anesthesia. The primary outcome was a relative risk of allergic reactions after propofol use for patients with egg/soybean allergy. RESULTS: In total, 22,111 patients with 28,710 anesthesia records were identified. Among patients with egg/soybean allergy, 173 (0.8%) patients and 237 (0.8%) anesthesia records were included in the study. Among the records of egg-/soybean-allergic patients, 151 were administered propofol, and 86 were not. The relative risk of allergic reactions after propofol use for patients with egg/soybean allergy was 1.14 (95% confidence interval, 0.10-12.4; p = 0.74). CONCLUSION: The use of propofol in patients with egg/soybean allergy does not significantly increase the relative risk of allergic reactions. Therefore, anesthesiologists can appropriately determine the indication for propofol, even in patients with egg/soybean allergy. TRIAL REGISTRATION: UMIN-CTN, UMIN000049321 registered 26 October 2022 - retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000056167.

Use of naldemedine is associated with reduced incidence of hyperactive delirium in cancer patients with opioid-induced constipation: A nationwide retrospective cohort study in Japan.

BACKGROUND: Medical benefits of peripherally acting mu-opioid receptor antagonists other than improving opioid-induced constipation remain unclear. Our aim was to evaluate the association between the use of naldemedine and incidence of hyperactive delirium in cancer patients receiving chemotherapy and opioid therapy. METHODS: We conducted a propensity score-matched analysis using a nationwide inpatient database in Japan. Cancer patients receiving both inpatient chemotherapy and opioid therapy from June 1, 2017, to March 31, 2018, were included. Patients receiving naldemedine were matched to control patients by propensity score. Our primary outcome was the incidence of hyperactive delirium during hospitalization, and secondary outcomes were the length of hospital stay, hospital costs, in-hospital mortality, and incidence of ileus. RESULTS: Of 34,031 patients receiving inpatient chemotherapy and opioid therapy, 1905 (5.6%) were included in the naldemedine group. After one-to-four propensity score matching, 1904 patients were included in the naldemedine group and 7616 in the control group. Naldemedine users had significantly reduced incidence of hyperactive delirium compared with the control patients (19.4% vs 23.3%; risk difference, -3.9 [95% confidence interval, -5.9 to -1.9]; risk ratio, 0.83 [0.75-0.92]; p<0.001; subdistribution hazard ratio, 0.85 [0.75-0.97]; p = 0.015). The median length of hospital stay was significantly shorter in the naldemedine group compared with the control group (12 days [interquartile range, 6-23] vs 14 days [6-26]; p = 0.001). The median hospital costs were also significantly lower in the naldemedine group compared with the control group (US $6179 [3351-10,026] vs US $6576 [3436-11,107]; p < 0.001). No significant differences were found for in-hospital mortality or incidence of ileus between the groups. CONCLUSIONS: Our findings suggest that the use of naldemedine may have benefits in preventing hyperactive delirium, shortening hospital stay, and decreasing hospital costs in cancer patients receiving chemotherapy and opioid therapy.

Elevation of serum plasminogen activator inhibitor-1 predicts postoperative delirium independent of neural damage: a sequential analysis.

Older adult surgical patients are susceptible to developing delirium. Early intervention can be initiated if a potential biomarker associated with delirium can be identified during the acute phase of surgery. Therefore, we investigated the changes in the levels of serum inflammatory mediators responsible for delirium. Serum biomarkers were measured preoperatively to postoperative day 3 in 96 patients who underwent esophageal cancer surgery and compared between patients who did and did not develop delirium. Serum concentrations of the brain-derived phosphorylated neurofilament heavy subunit remained at higher levels throughout the entire perioperative period in patients with delirium (n = 15) than in those without delirium (n = 81). The interaction between delirium and non-delirium was significant for plasminogen activator inhibitor-1 (including age as a covariate, F = 13.360, p < 0.0001, η2 p = 0.134, observed power 1.000) during the perioperative periods. Plasminogen activator inhibitor-1 level discriminated between patients with and without clinically diagnosed delirium with significantly high accuracy (area under curve, 0.864; sensitivity, 1.00: negative predictive value, 1.000; p = 0.002). Rapid increases in the levels of serum plasminogen activator inhibitor-1 may enable clinicians to identify patients at risk of developing postoperative delirium and initiate early prevention and intervention.

Serum levels of apolipoprotein A-I and E are associated with postoperative delirium: A post hoc analysis.

Postoperative delirium is a common complication for elderly patients. Detection of phosphorylated neurofilament heavy subunit in the serum reflects axonal damage with postoperative delirium. Although it has been implicated that serum apolipoprotein levels might be associated with senile cognitive disorder, its role in the development of delirium has not been fully investigated. This study examined the association of apolipoproteins with delirium after surgery. This was a post hoc analysis of 117 patients who participated in a prospective observational study of delirium in patients undergoing cancer surgery. Patients were clinically assessed for delirium within the first 5 days of surgery. Serum levels of apolipoprotein A-I, B, and E were measured on postoperative day 3. Forty-one patients (35%) were clinically diagnosed with postoperative delirium. Serum levels of apolipoprotein A-I and B were increased in patients with delirium whereas those of apolipoprotein E were decreased. These changes in apolipoprotein A-I and E levels were associated with the presence of phosphorylated neurofilament heavy subunit in the serum, and were significantly associated with delirium (A-I: adjusted odds ratio [aOR], 6.238; 95% confidence interval [CI], 2.766-20.68; P < .0001; E: aOR, 0.253; 95% CI, 0.066-0.810; P = .0193). A combination of apolipoprotein A-I and E offers significant discrimination between delirium and nondelirium with high accuracy (area under the curve, 0.8899). Serum apolipoprotein A-I and E levels were associated with delirium and the presence of phosphorylated neurofilament heavy subunit in serum. Therefore, apolipoproteins might be useful biomarkers of postoperative delirium.

Efficacy of treatments for pain and numbness in cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Pain and numbness in cancer survivors frequently have negative impacts on quality of life (QoL). This meta-analysis aimed to identify the current treatment options for pain and numbness in cancer survivors and to evaluate their effects. METHODS: Cancer survivors were defined as patients diagnosed with cancer who had completed active cancer treatment, whose conditions were stable, and who had no evidence of recurrent or progressive disease. A systematic search through the PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, PsycInfo, and CINAHL databases was conducted, which targeted randomized controlled trials (RCTs) published until April 2022 that evaluated any type of treatment for pain or numbness in cancer survivors. A meta-analysis was conducted using the random-effects model to obtain the effect sizes of 7 types of treatments: opioid therapy, nonopioid pharmacotherapy, interventional therapy, acupuncture, education/cognitive behavioral therapy (CBT), physical exercise, and alternative medicine. RESULTS: A total of 36 studies involving 2,870 cancer survivors were included. Among them, 35 (n=2,813) were included in the meta-analysis for pain. The analysis suggested that physical exercise [n=761; 13 studies; standardized mean difference (SMD) -0.84; 95% confidence interval (CI): -1.14 to -0.55], acupuncture (n=409; 3 studies; SMD -0.80; 95% CI: -1.04 to -0.56), and alternative medicine (n=206; 6 studies; SMD -0.44; 95% CI: -0.71 to -0.16) could significantly reduce pain. Nonopioid pharmacotherapy and education/CBT did not demonstrate significant effects. No studies were identified that investigated the effects of opioid therapy or interventional therapy on pain. Regarding numbness, 5 studies (n=566) were included in the meta-analysis. Acupuncture (n=99; 2 studies) did not demonstrate significant effects on numbness, and the effects of nonopioid pharmacotherapy, education/CBT, and physical exercise could not be determined due to the small number of included studies. No studies were identified that investigated the effects of opioid therapy, interventional therapy, or alternative medicine on numbness. CONCLUSIONS: This meta-analysis suggested that physical exercise, acupuncture, and alternative medicine may reduce pain in cancer survivors, with a very small to moderate amount of evidence. The effect of treatments for numbness could not be determined due to the limited number of included studies. Further studies are needed, particularly on widely used pharmacotherapy.

Imaging features inferring symptom onset due to spinal metastasis progression: a preliminary study.

BACKGROUND: Spinal metastases can cause intractable pain and neurological deficits, which can markedly worsen both patients' activities of daily living (ADL) and their health-related quality of life (QOL). Early intervention is essential to prevent irreversible neurological deficits and pain associated with spinal metastases. We investigated the imaging features of spinal metastases that led to neurological deficits. METHODS: We analyzed axial cross-sectional computed tomography (CT) images of cervical and thoracic spinal metastases in patients with and without lower limb motor paralysis, neuropathic pain, and local nociceptive pain. We distinguished regions of the spine associated with these respective symptoms, and explored their inferable performance using images obtained before symptom onset. In addition, we analyzed the imaging features and type of bone metastasis (osteolytic and osteoblastic). RESULTS: Spinal lesions occupied the area in and around the spinal canal and around the pedicle in patients with motor paralysis. Lesions around the pedicle and in the most posterior vertebral body part before symptom onset were inferable. In patients with neuropathic pain, spinal metastases spread along the pedicle before symptom onset, and had surrounded the spinal canal circumferentially at symptom onset. Local nociceptive pain was more common near the center of the vertebral body either at or before symptom onset. There was no difference in the imaging features according to the type of bone metastasis. CONCLUSIONS: Lesions in certain regions in the asymptomatic metastatic spine can indicate the onset of spinal metastasis-related symptoms in the next few months. Early therapeutic intervention might be applied to prevent neurological disorder.

Different Profiles of the Triad of Lysophosphatidylcholine, Lysophosphatidic Acid, and Autotaxin in Patients with Neuropathic Pain Diseases: a Preliminary Observational Study.

The mechanisms underlying neuropathic pain remain unclear. Lysophosphatidic acid (LPA) is a bioactive phospholipid derived mainly from lysophosphatidylcholine (LPC) by extracellular autotaxin (ATX), and has attracted attention as a candidate biomarker of neuropathic pain. We aimed to investigate the levels of LPA, LPC, and ATX in patients with lumbar spinal canal stenosis (LSCS) or other neuropathic pain diseases, and to distinguish the underlying mechanism of LSCS from other neuropathic pain conditions. Furthermore, the levels of phosphorylated neurofilament heavy chain (pNF-H), an objective surrogate marker of axonal damage, were also measured. Cerebrospinal fluid (CSF) samples were obtained from 56 patients with LSCS (n = 31) and various etiologies other than LSCS (n = 25). Patients with LSCS complained of pain intensity comparable to that of patients without LSCS. The LPA levels were significantly higher in patients with LSCS than in non-LSCS patients, while the ATX levels were significantly lower. However, the differences in LPC and pNF-H levels between the two patient groups were not significant. The LPA/LPC ratio was significantly higher in the LSCS group. Notably, the difference in LPA between the two groups diminished in the analysis of covariance (ANCOVA) with ATX as a covariate. Thus, it helped to reveal that LPA synthesis in patients with LSCS depends more efficiently on ATX than in non-LSCS neuropathic pain patients with other etiologies. Our findings further suggest that the triad of LPA, LPC, and ATX in LSCS may contribute to the development and maintenance of neuropathic pain in a manner different from non-LSCS neuropathic conditions.

Peripheral nerve field stimulation successfully manages axial pain after posterior cervical spine surgery: case report.

Axial neck and back pain after cervical spinal surgery is a common postoperative complication and can last for years. It is sometimes refractory to conventional treatments such as pharmacotherapy and spinal cord stimulation (SCS). Peripheral nerve field stimulation (PNFS) was recently introduced as an alternative treatment in the management of axial back pain into the occipital/craniofacial region and trunk in occipital neuralgia, post-herpetic neuralgia, and low back pain after lumbar spine surgery. However, PNFS has not been applied to axial neck pain. The patient suffered from occipital neuralgia and axial back pain after cervical spine surgery. In addition to PNFS of the greater occipital nerves for occipital neuralgia, we subcutaneously implanted two electrodes into the bilateral neck regions parallel with a sequential arrangement of the cervical spine. The electrodes were placed immediately above the trapezius muscles and electrical paresthesia was enhanced by posterior neck muscle twitches, fully covering the areas with axial neck pain. Both electrodes successfully achieved an almost 70% decrease in occipital and axial neck pain. Since axial neck pain after cervical spinal surgery often affects patients' health-related quality of life, neuromodulation in the form of PNFS may have the potential to become a novel alternative to conventional pain treatments for medically refractory axial neck pain.

Capecitabine-induced hand-foot syndrome does not emerge in the complex regional pain syndrome-affected limb: A case report.

Hand-foot syndrome (HFS) is a frequent adverse effect of various anti-tumour drugs, such as capecitabine, that affects their dose-limiting toxicity. The mechanism of HFS remains unknown and there are currently no effective strategies to treat HFS, except for cessation. The current study presented a female case where one hand, affected by brachial plexus infiltration due to the subclavian lymph node metastasis of breast cancer, exhibited not only pain and partial motor paralysis but also anhidrosis, oedema and skin colour changes. The patient met the diagnostic criteria for complex regional pain syndrome (CRPS). After treatment with capecitabine, their anhidrosis hand completely prevented HFS. The other hand and both feet demonstrated typical symptoms of HFS, which improved consequent to capecitabine cessation. The CRPS-affected hand remained normal. Considering the limited presentation of HFS concomitant with anhidrosis, the exocrine release of condensed capecitabine through sweat glands might be a promising mechanism of HFS induction.

Exponential correlations among neuropathic components, pain intensity, and catastrophic thoughts in patients with musculoskeletal pain disorder.

BACKGROUND: Neuropathic components and catastrophic thoughts contribute to the quality of life impairments in patients with chronic pain. This retrospective cross-sectional observational study examined the extent to which neuropathic components affect pain intensity and catastrophic thoughts using a mathematical model. METHODS: Participants with chronic pain with spinal or joint disorders were rated for pain intensity using a numerical rating scale (NRS), painDETECT questionnaire (PDQ), and pain catastrophizing scale (PCS). We plotted to scatter plots between PDQ and either NRS or PCS and drew best-fit lines for patients with leg pain only. We divided patients with both leg and back pain into two clusters: located above or below the baselines, and then we drew the best-fit lines for each cluster. We performed factor analysis on PDQ items and developed and validated a discriminant to identify patients located above the baseline in another cohort of musculoskeletal disorders. RESULTS: We analyzed 163 patients with lumbar disorders and 205 patients with joint disorders. PDQ correlated exponentially with NRS and PCS of the patients located above the baseline in both disorder groups and correlated linearly or logarithmically in patients located below the baseline. Factor analysis revealed three sets of pain characteristics for each disorder. We developed the discriminant from PDQ items to identify patients showing exponential correlations and then validated it in another cohort of 137 patients. The coefficient for "pressure-evoked pain" was the highest in the discriminant. CONCLUSIONS: Mathematical models indicate neuropathic components demonstrate linear correlations with NRS and PCS generally, but exponential correlations in a cluster of the patients with musculoskeletal pain. We developed and validated the discriminant based on pain characteristics to identify such patients; "pressure-evoked pain" was the most significant contributor.

Elevated neuron-specific enolase level is associated with postoperative delirium and detection of phosphorylated neurofilament heavy subunit: A prospective observational study.

BACKGROUND: Delirium is the most common central nervous system complication after surgery. Detection of phosphorylated neurofilament heavy subunit in the serum reflects axonal damage within the central cervous system and is associated with the severity of postoperative delirium. Neuron-specific enolase and S100 calcium-binding protein ß have been identified as possible serum biomarkers of postoperative delirium. This study examined the association of the levels of these markers with incidence of postoperative delirium and detection of phosphorylated neurofilament heavy subunit. METHODS: This study represents a post hoc analysis of 117 patients who participated in a prospective observational study of postoperative delirium in patients undergoing cancer surgery. Patients were clinically assessed for development of postoperative delirium within the first five days of surgery. Serum levels of phosphorylated neurofilament heavy subunit, neuron-specific enolase, and S100 calcium-binding protein ß levels were measured on postoperative day 3. RESULTS: Forty-one patients (35%) were clinically diagnosed with postoperative delirium. Neuron-specific enolase level (P < 0.0001) and the proportion of patients positive for phosphorylated neurofilament heavy subunit (P < 0.0001) were significantly higher in the group of patients with postoperative delirium. Neuron-specific enolase level discriminated between patients with and without clinically diagnosed postoperative delirium with significantly high accuracy (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.79-0.95; P < 0.0001). Neuron-specific enolase level was associated with incidence of postoperative delirium independently of age (adjusted odds ratio, 8.291; 95% Cl, 3.506-33.286; P < 0.0001). The AUC for the serum neuron-specific enolase level in detecting phosphorylated neurofilament heavy subunit was significant (AUC, 0.78; 95% CI, 0.66-0.90; P < 0.0001). CONCLUSION: Elevated serum neuron-specific enolase was associated with postoperative delirium independent of age as well as detection of phosphorylated neurofilament heavy subunit in serum. Serum neuron-specific enolase and phosphorylated neurofilament heavy subunit might be useful as biomarkers of postoperative delirium. TRIAL REGISTRATION: University Medical Information Network (UMIN) trial ID: UMIN000010329; https://clinicaltrials.gov/.