Musculoskeletal Pain and the Prevalence of Rheumatoid Arthritis in Breast Cancer Patients During Cancer Treatment: A Retrospective Study

PurposeBreast cancer patients often develop musculoskeletal pain, resembling that experienced by patients with rheumatoid arthritis (RA), during cancer treatment. This study aimed to investigate the causes of musculoskeletal pain, including RA, among breast cancer patients.MethodsThis retrospective study included breast cancer patients experiencing new-onset arthralgia during cancer treatment along with age- and sex-matched controls without breast cancer, who were evaluated at the Rheumatologic clinic between 2004 and 2017. The causes of musculoskeletal pain were compared between breast cancer patients and controls. The effects of cancer treatment on arthralgia and factors associated with RA were examined.ResultsA total of 146 breast cancer patients and 102 controls were included in the final analysis. The most common cause of arthralgia during breast cancer treatment was osteoarthritis (OA, 61.0%), followed by enthesopathy/tendinopathy (28.1%), which included tendinitis, adhesive capsulitis, and carpal tunnel syndrome. Overall, 50.0% of 72 breast cancer patients receiving aromatase inhibitors (AIs) satisfied the criteria of AI-induced musculoskeletal symptoms (AIMSS). The mean symptom duration (i.e., the time between pain onset and evaluation by a rheumatologist) was shorter in breast cancer patients than in controls (7.0 ± 12.1 vs. 14.8 ± 24.9 months, respectively; p = 0.004). RA was diagnosed in 3 (2.1%) breast cancer patients and 3 (2.9%) controls. All breast cancer patients with RA had an elevated erythrocyte sedimentation rate (ESR, 66.7 ± 25.0 mm/h), whereas those without RA had a normal ESR (20.4 ± 21.5 mm/h). Patients with breast cancer required more analgesics than the controls.ConclusionOA and enthesopathy/tendinopathy are the most common causes of arthralgia in breast cancer patients, which may concurrently manifest as AIMSS. Patients with breast cancer did not have a higher prevalence of RA than those without breast cancer.     

Annual Case Volume and One-Year Mortality for Endovascular Treatment in Acute Ischemic Stroke

BackgroundThe association between endovascular treatment (EVT) case volume per hospital and clinical outcomes has been reported, but the exact volume threshold has not been determined. This study aimed to examine the case volume threshold in this context.MethodsNational audit data on the quality of acute stroke care in patients admitted via emergency department, within 7 days of onset, in hospitals that treated ≥ 10 stroke cases during the audit period were analyzed. Ischemic stroke cases treated with EVT during the last three audits (2013, 2014, and 2016) were selected for the analysis. Annual EVT case volume per hospital was estimated and analyzed as a continuous and a categorical variable (in quartiles). The primary outcome measure was 1-year mortality as a surrogate of 3-month functional outcome. As post-hoc sensitivity analysis, replication of the study results was examined using the 2018 audit data.ResultsWe analyzed 1,746 ischemic stroke cases treated with EVT in 120 acute care hospitals. The median annual EVT case volume was 12.0 cases per hospital, and mortality rates at 1 month, 3 months, and 1 year were 12.7%, 16.6%, and 23.3%, respectively. Q3 and Q4 had 33% lower odds of 1-year mortality than Q1. Adjustments were made for predetermined confounders. Annual EVT case volume cut-off value for 1-year mortality was 15 cases per year (P < 0.02). The same cut-off value was replicated in the sensitivity analysis.ConclusionAnnual EVT case volume was associated with 1-year mortality. The volume threshold per hospital was 15 cases per year.     

Catechin-7-O-α-L-rhamnopyranoside can reduce α-MSH-induced melanogenesis in B16F10 melanoma cells through competitive inhibition of tyrosinase

Although melanogenesis is a defense mechanism against ultraviolet (UV)-induced skin damage, abnormally excessive melanin production causes pigmentation disorders. Tyrosinase, as a key factor for melanin synthesis, plays an important role in inducing skin pigmentation. Therefore, the inhibition of tyrosinase is crucial in preventing skin pigmentation in the cosmetics and medicine fields. However, the majority of well-known tyrosinase inhibitors have been discontinued due to toxic effects on the skin or lack of selectivity and/or stability. In this study, we evaluated possible anti-melanogenic effects of catechin-7-O-α-L-rhamnopyranoside (C7R) isolated from the stem bark of Ulmus parvifolia, to discover a new tyrosinase inhibitor that has both safety and stability. When C7R was pretreated in B16F10 melanoma cells stimulated by α-melanocyte-stimulating hormone, this compound reduced melanin accumulation and murine tyrosinase activity. In line with these results, C7R inhibits tyrosinase purified from a mushroom in vitro like kojic acid and arbutin. Furthermore, C7R exhibited a competitive inhibition on a Lineweaver-Burk plot. Next, the underlying mechanisms of the C7R-mediated tyrosinase inhibitory effect were sought through docking simulation and pharmacophore analysis between tyrosinase residues and C7R. The results of these analyses showed that C7R had binding energy of -14.5kcal/mol, and indicated that C7R interacts with tyrosinase through an aromatic ring and various hydrophobic and hydrogen bonds. Together, our results suggest that C7R can be applied as a novel natural anti-melanogenic agent that inhibits tyrosinase.     

Antiangiogenic activity of lupeol from Bombax ceiba

In the search for antiangiogenic agents from medicinal plants used in Vietnam, a methanol extract of the stem barks of Bombax ceiba was found to exhibit a significant antiangiogenic activity on in vitro tube formation of human umbilical venous endothelial cells (HUVEC). Bioactivity-guided fractionation and isolation carried out on this extract afforded lupeol as an active principle. At 50 and 30 microg/mL lupeol showed a marked inhibitory activity on HUVEC tube formation while it did not affect the growth of tumor cell lines such as SK-MEL-2, A549, and B16-F10 melanoma.     

Vitexin, orientin and other flavonoids from Spirodela polyrhiza inhibit adipogenesis in 3T3-L1 cells

To investigate the adipogenesis inhibitory effect on lipid accumulation, 3T3-L1 cells were treated with fractions and isolated flavonoids of Spirodela polyrhiza. An ethanol extract of S. polyrhiza was fractionated into three fractions. The butanol soluble fraction (SPB) exhibited potent antiadipogenesis activity and decreased C/EBPα and PPARγ protein expression level in 3T3-L1 cells without significant cytotoxicity. The flavonoids were isolated from SPB and their chemical structures were identified as chrysoeriol (1), apigenin (2), luteolin (3), vitexin (4), cosmosin (5), orientin (6) and luteolin-7-O-β-d-glucoside (7) by spectroscopic analysis. Studies on the adipogenesis and intracellular triglyceride accumulation inhibitory effect showed that compounds 4 and 6 had the highest activity and decreased C/EBPα and PPARγ protein expression level in 3T3-L1 cells. These results suggest that the flavonoids isolated from SPB, especially compounds 4 and 6, contribute to the inhibitory activity of S. polyrhiza in 3T3-L1 cells.     

Stilbenes and oligostilbenes from leaf and stem of <Emphasis Type="Italic">Vitis amurensis</Emphasis> and their cytotoxic activity

Chromatographic separation of the EtOAc fraction from the leaf and stem of Vitis amurensis led to the isolation of six oligostilbenoids (i.e., r-2-viniferin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), gnetin H (4), amurensin G (5), (+)-ampelopsin A (8)) and four stilbenoids (i.e., trans-resveratrol (6), (+)-ampelopsin F (7), piceatannol (9), and trans-piceid (10)). The structures have been identified on the basis of spectroscopic evidence and physicochemical properties. The isolates were investigated for cytotoxic activity against three cancer cell lines in vitro using the MTT assay method. Amurensin G (5) and trans-resveratrol (6) showed significant cytotoxic activity against L1210, K562 and HTC116 cancer cell lines with IC₅₀ values ranging from 15.7 ± 2.1 to 30.9 ± 1.8 μM. (+)-Ampelopsin A (8) and trans-piceid (10) exhibited considerable cytotoxic activity against L1210 (IC₅₀ values of 30.6 ± 4.1 and 28.7 ± 2.81 μM, respectively) and K562 (IC₅₀ values of 38.6 ± 0.82 and 24.6 ± 0.76 μM, respectively). Gnetin H (4) showed only weak cytotoxic activity against L1210 with an IC₅₀ value of 40.1 ± 4.23 μM. On the other hand, r-2-viniverin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), (+)-ampelopsin F (7), and piceatannol (9) exhibited no activity on three cancer cell lines.     

Giant cell hepatitis with autoimmune hemolytic anemia in a Korean infant

Giant cell hepatitis (GCH) with autoimmune hemolytic anemia (AHA) is a very rare disease characterized by early onset and severe clinical manifestations, including immune hemolytic anemia and hepatitis with cholestasis. The prognosis is poor despite aggressive immunosuppressive therapy. We report here the first case of GCH with AHA in East Asia. A 2‐month‐old boy was admitted with jaundice. Blood test indicated abnormal liver function and low hemoglobin. Direct Coombs test and several autoantibodies associated with liver disease were positive, and liver biopsy was consistent with GCH. He was treated with prednisolone and ursodeoxycholic acid, and at the time of writing was in clinical and biochemical remission after prednisolone was stopped.     

Multivisceral transplantation for abdominal tumors in children: A single center experience and review of the literature

Standard management of intra‐abdominal pediatric solid tumors requires complete resection. However, tumors with multiple organ and vascular involvement present a unique surgical challenge. We conducted a retrospective chart review of four patients, aged 2‐14 years, undergoing MVT for intra‐abdominal tumors with significant involvement of the visceral arteries and/or portomesenteric venous system at our institution. Indications for MVT included hepatocellular carcinoma, inflammatory myofibroblastic tumor, and two cases of hepatoblastoma. Grafts included liver, stomach, small bowel, and pancreas in all patients, with two patients also receiving spleens, and one, a partial esophageal transplant. Median hospital stay was 80 days. Postoperative complications included reoperation for abdominal hematoma and bowel obstruction, steroid responsive intestinal rejection, wound dehiscence, fungemia, seizures, and chyle leak with pleural effusion. One patient developed Epstein‐Barr virus‐associated complications which responded well to treatment. On follow‐up (range 2.8‐7.8 years), all patients have satisfactory graft function and no evidence of recurrent disease. MVT is an effective means of achieving complete gross resection of intra‐abdominal malignancies in patients with multiple organ and vascular involvement.     

Inhibitory effects of casticin on migration of eosinophil and expression of chemokines and adhesion molecules in A549 lung epithelial cells via NF-κB inactivation

Ethnopharmacological relevance

The fruits of Vitex rotundifolia L. have long been used for the treatment of inflammation of the respiratory tract in East Asia.

Aim

To determine if casticin, one of the constituents of Vitex rotundifolia L., has anti-allergic and anti-inflammatory effects in asthma.

Materials and methods

The in vitro anti-inflammatory activity of casticin was studied in A549 human type II-like epithelial lung cells using an eotaxin inhibition assay. Additionally, its effects on eotaxin, regulated on activation normal T cell expressed and secreted (RANTES), vascular cell adhesion molecule (VCAM)-1, and inter-cellular adhesion molecule (ICAM)-1 expression were investigated by real time-polymerase chain reaction (real time-PCR). The inhibition of nuclear factor κB (NF-κB) activity in the presence of casticin was determined by analyzing confocal microscopy images of fluorescence immunocytochemical analysis while the suppression of inhibitory κB (IκB)-α phosphorylation was studied using Western blot analysis. Finally, the inhibitory effect of casticin on eosinophil migration toward prestimulated A549 cell media was measured using the human eosinophilic leukemia cell line.

Results and discussion

Casticin significantly suppressed eotaxin production in cytokine activated A549 lung epithelial cells. Casticin also suppressed the mRNA expression levels of eotaxin, RANTES, VCAM-1, and ICAM-1, which subsequently contributed to the inhibition of eosinophil migration. Furthermore, casticin inhibited IκB-α phosphorylation and nuclear translocation of p65 in A549 cells.

Conclusion

Casiticin inhibited the eosinophil migration and activity of chemokines and adhesion molecules involved in the inflammatory process of asthma by suppressing the NF-κB pathway. These results suggest that casticin has the potential for use in the treatment of allergic asthma.