A multicenter study of romiplostim for chemotherapy-induced thrombocytopenia in solid tumor s and hematologic malignancies

Chemotherapy-induced thrombocytopenia (CIT) frequently complicates cancer treatment causing chemotherapy treatment delays, dose reductions, and discontinuation. There is no US Food and Drug Administration (FDA)-approved agent available to manage CIT. This study retrospectively evaluated patients with CIT treated on institutional romiplostim treatment pathways at four US centers. The primary outcome was achievement of a romiplostim response (median on-romiplostim platelet count ≥75x10⁹/L and ≥30x10⁹/L above baseline). Secondary outcomes included time to platelet count ≥100x10⁹/L and rates of the following: platelet count <100×10⁹/L, platelet count <75x10⁹/L, platelet count <50x10⁹/L, thrombocytosis, chemotherapy dose reduction/treatment delay, platelet transfusion, bleeding, and thromboembolism. Multivariable regression was used to identify predictors of romiplostim non-response and compare weekly dosing with intracycle/intermittent dosing. A total of 173 patients (153 solid tumor, 20 lymphoma or myeloma) were treated, with 170 (98%) receiving a median of four (range: 1-36) additional chemotherapy cycles on romiplostim. Romiplostim was effective in solid tumor patients: 71% of patients achieved a romiplostim response, 79% avoided chemotherapy dose reductions/treatment delays, and 89% avoided platelet transfusions. Median per-patient platelet count on romiplostim was significantly higher than baseline (116x10⁹/L vs. 60x10⁹/L; P<0.001). Bone marrow (BM) tumor invasion, prior pelvic irradiation, and prior temozolomide exposure predicted romiplostim non-response. Bleeding rates were lower than historical CIT cohorts and thrombosis rates were not elevated. Weekly dosing was superior to intracycle dosing with higher response rates and less chemotherapy dose reductions/treatment delays/bleeding; intracycle dosing had an incidence rate ratio (IRR) for dose reduction/treatment delay of 3.00 (95%CI: 1.30-6.91; P=0.010) and an IRR for bleeding of 4.84 (95%CI: 1.18-19.89, P=0.029) compared with weekly dosing. Blunted response (10% response rate) was seen in non-myeloid hematologic malignancy patients with BM involvement. In conclusion, romiplostim was safe and effective for CIT in most solid tumor patients.     

CD44‐Targeted Docetaxel Conjugate for Cancer Cells and Cancer Stem‐Like Cells: A Novel Hyaluronic Acid‐Based Drug Delivery System

A CD44‐targeted macromolecular conjugate of docetaxel was prepared via a pH‐sensitive linkage to hyaluronic acid and was characterized using NMR, gel permeation chromatography, and differential scanning calorimetry. The conjugated species were further evaluated in terms of drug release, cytotoxicity, cellular uptake, cell cycle inhibition, and subacute toxicity in mice. Cellular microscopic studies revealed that CD44‐expressing cells including MCF‐7 cancer stem cells and MDA‐MB‐231 metastatic breast cancer cells had internalized the conjugates via a selective receptor‐mediated mechanism, leading to cell cycle arrest in the G2/M phase. Hyaluronic acid–docetaxel conjugates showed specific toxicity only in CD44‐expressing cells in vitro, along with a decreased risk of neutropenia and dose‐dependent mortality in vivo. Hyaluronic acid–drug conjugates represent a promising and efficient platform for solubilization of sparingly soluble molecules as well as active and selective targeted delivery to cancer cells and cancer stem cells.     

First reported case of delayed‐type hypersensitivity reaction to non‐hyaluronic acid Polycaprolactone dermal filler following COVID‐19 vaccination: A case report and a review of the literature

Cases of filler reactions after COVID‐19 vaccination have been reported. Here, we present the first case of delayed‐type reaction (DTR) to non‐hyaluronic acid Polycaprolactone dermal filler after the second dose of Sinopharm COVID‐19 vaccine which was improved with administration of topical and intralesional steroids.     

Mutational analysis of enhancer domains responsive to trans-activation by the X gene of human hepatitis B virus

Summary The X gene product of human hepatitis B virus (HBV) trans-activates the HBV enhancer. In order to identify domains responsive to trans-activation by the X gene, we introduced a series of mutations into the HBV enhancer and assayed the enhancer activities in the presence of the X gene product. Our results suggest that the EP domain of the enhancer is essential for trans-activation by the X gene.     

Antineoplastic activity of Solidago virgaurea on prostatic tumor cells in an SCID mouse model

Solidago virgaurea (goldenrod) has traditionally been used as an anti-inflammatory herbal medicine for the treatment of various symptoms, including prostatic diseases. The plant has also been reported to have antibacterial, spasmolytic, and carminative properties. During the course of our screening for antineoplastic activities in various herbal plants, we found that the extract of S. virgaurea exhibits strong cytotoxic activities on various tumor cell lines. The active component mostly resides in the leaves of the plant and is soluble in water. When the extract was fractionated by a Sephadex G-100 column, the active fraction corresponded to a molecular weight of approximately 40,000. This cytotoxic activity is effective on various tumor cell lines, including human prostate (PC3), breast (MDA435), melanoma (C8161), and small cell lung carcinoma (H520). To examine the effect of the cytotoxic activity on tumor cells in vivo, we used the rat prostate cell line (AT6.1) and an SCID mouse model. AT6.1 cells were injected into the flank of SCID mice, and then the G-100 fraction of S. virgaurea was administered intraperitoneally or subcutaneously every 3 days. The size of the tumor was measured for up to 25 days. The growth of the tumor was significantly suppressed by the G-100 fraction at 5 mg/kg without any apparent side effects. Therefore, S. virgaurea is considered to be promising as an antineoplastic medicine with minimal toxicities.     

The effect of large-dose intrathecal opioids on the autonomic nervous system

Decreases in blood pressure after the spinal injection of opioids suggest that intrathecal (IT) opioids may have a sympatholytic effect similar to that of local anesthetic drugs. We compared two groups of patients aged 10-16 yr (n = 10 in each group). Group One (IT group) received IT opioids. Group Two (Epidural group) received 0.5% bupivacaine epidurally. The sympathetic effects of IT opioids and epidural bupivacaine were monitored by the changes in toe relative to calf temperature and by the changes in pulse wave gradients with digital plethysmography. Changes in temperature gradients comparing calf to toe and increases in pulse amplitude indicate vasodilatation caused by sympathetic blockade in this model. Calf to toe temperature gradients (Deltacalf-Deltatoe) were evaluated by subtracting the two measurements. Pulse wave plethysmography was recorded before and after spinal and epidural injection at intervals of 10 min for 40 min. All patients demonstrated changes in their calf to toe gradients after IT and epidural injections (-3.2 +/- 1.6). Systolic blood pressure decreased from a mean of 70 +/- 15 mm Hg to 55 +/- 10 mm Hg. Pulse wave plethysmography amplitude increased after the intrathecal opioid and epidural bupivacaine injection similarly. We conclude that the increases in pulse wave amplitude and decreases in calf-toe gradients indicate a sympatholytic effect after IT opioids similar to that of local anesthetics. IMPLICATIONS: The sympatholytic effects of neuraxial opioids were compared with those of local anesthetics. Two groups of patients were assigned to receive a neuraxial opioid or bupivacaine. Our results demonstrate that opioids cause hypotension and peripheral vasodilatation similar to bupivacaine. This finding suggests that neuraxial opioids have a sympatholytic effect comparable to that of local anesthetic drugs.     

Comparison of oral pentazocine, oral diazepam and intramuscular pentazocine for paediatric premedication

Oral pentazocine-atropine, oral diazepam-atropine and IM pentazocine-atropine were compared as preoperative medication in children. Observations in 300 children ages 1-14 years included the emotional state at time of induction of anaesthesia, smoothness of induction, dryness of oral mucosa and tongue, incidence of vomiting, and emotional state and length of stay in the recovery room. The incidence of a calm state at the time of induction and smoothness of induction of anaesthesia was the same following oral and IM premedication. There was satisfactory drying of salivary secretions. The incidence of vomiting in the recovery room was the same following oral and IM premedication. However, children in age groups 1-4 and 5-9 years who received diazepam-atropine were more restless in the recovery room than those who received oral or IM pentazocine-atropine. More children in groups 1-4 and 5-9 years who received IM pentazocine-atropine stayed longer in the recovery room. We conclude that oral diazepam-atropine and oral pentazocine-atropine are comparable as to preoperative medication IM pentazocine-atropine and that they can be given as an alternate to intramuscular injection.