Clinical characteristics, treatment, and outcomes of nivolumab induced immune thrombocytopenia.

Immune thrombocytopenia (ITP) represents an uncommon hematological side effect associated with nivolumab, and its distinct clinical attributes remain poorly defined. This research aimed to explore the clinical manifestations and outcomes of ITP induced by nivolumab. Reports on nivolumab induced ITP up to April 30, 2024, were collected for retrospective analysis. The study involved 34 patients with a median age of 67 years (range 32, 82). The onset of ITP varied from 10 to 100 days post initial dosage, with a median onset at 70 days. The majority of patients exhibited no symptoms, with only 23.5% experiencing clinically significant bleeding and 11.8% facing non-clinically significant bleeding. The median platelet count was 12 × 109/L (range 0, 115), with 67.6% of patients having platelet levels below 25 × 109/L. Bone marrow biopsy revealed mainly elevated megakaryocytes. Platelet-associated IgG levels were elevated with a median of 210 ng/107 cells (range 73, 1130). Subsequent interventions, which included cessation of nivolumab, administration of systemic corticosteroids, intravenous immunoglobulin therapy, a thrombopoietin receptor agonist, platelet transfusion, and rituximab treatment, resulted in 82.4% of subjects achieving normalized platelet counts, whereas 5.9% passed away due to ITP. ITP is a rare life-threatening immune-related adverse event and necessitates close monitoring. Systemic steroids are the primary treatment for ITP, while intravenous immunoglobulin, thrombopoietin receptor agonist and rituximab are other options.

Clinical characteristics, treatment, and outcomes of pembrolizumab-induced uveitis.

Pembrolizumab has been associated with episodes of uveitis, and the clinical characteristics between them are unknown. The aim of this study was to investigate the clinical characteristics of pembrolizumab-induced uveitis and to provide reference for prevention, diagnosis and treatment. We collected studies related to pembrolizumab-induced uveitis by searching databases for retrospective analysis until April 30, 2024. The median age of the 31 patients was 63 years (range 7, 82), and the median duration of uveitis onset was 12 weeks (range 0.4, 108). Decreased vision (41.9%) and blurred vision (25.8%) were the most common complaints. Uveitis can be manifested as Vogt-Koyanagi-Harada disease-like uveitis (22.6%) and Birdshot uveitis (6.5%). Uveitis mainly affects both eyes and is related to anterior uveitis (35.5%), panuveitis (25.8%) and posterior uveitis (19.4%). Patients receiving topical steroid drops, systemic steroids, and withdrawal of pembrolizumab significantly improved symptoms at a median time of 4 weeks (range 2, 16). The possibility of uveitis should be considered when patients are treated with pembrolizumab and experience eye symptoms such as blurred vision and decreased vision. Depending on the severity of uveitis, treatment with topical and systemic steroids may be selected.

Clinical characteristics, treatment and outcome of clindamycin induced acute generalized exanthematous pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction to clindamycin. This study investigated the clinical features of clindamycin-induced AGEP and provided reference for the prevention and treatment of AGEP. Case reports, case series and clinical studies of clindamycin-induced AGEP were collected by retrieving English and Chinese database from inception until May 31, 2024. Of the 35 patients included, 25 (71.4%) were female, and the median age was 57 years (1.6-88 years). The duration of AGEP onset is 2 days (range 0.04,13) after initial administration. The main clinical morphology of AGEP is a non-follicular pustular on an erythematous base, which may be accompanied by fever (54.3%) and pruritus (40.0%). These lesions mainly involved extremities and trunk. The median elevated neutrophil count was 13.3 × 109/L (range 10.3, 31.4). Histologic features of AGEP are characterized by intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophilic, lymphocytic, andeosinophilic infiltrates. Patients gradually recovered after the withdrawal of clindamycin and supportive therapy with a median time of 9 days (range 2, 30). Clinicians should be aware of AGEP as a rare adverse effect of clindamycin. When clindamycin is prescribed, it should be stopped in time when AGEP occurs, and active systemic treatment should be given. AGEP is a self-limiting disease with a good prognosis.

Identification of anti-nociceptive constituents from the pollen of Typha angustifolia L. using effect-directed fractionation.

The pollen of T. angustifolia, also known as Pu huang in Chinese, has been used for treatment of stranguria, hematuria, dysmenorrhea, metrorrhagia and injuries in China for a long time. Extensive efforts have been directed toward its phytochemical and biological aspects. However, little is known about its anti-nociceptive implication and material basis. This work presented the investigation of the anti-nociceptive effect of Typhae Pollen using an effect-directed fractionation strategy, thereby leading to identification of isorhamnetin-3-O-neohesperidin (1) and typhaneoside (2), together with other minor flavonoid glycoside congeners, as the main anti-nociceptive constituents. This work not only unveils the anti-nociceptive potential of Typhae Pollen, but also establishes a method to enrich and identify the anti-nociceptive constitutes of Typhae Pollen. Moreover, this work is a successful example of effect-directed fractionation strategy, which represents a powerful tool in TCM-based drug discovery and development.

Polyphenolic glycosides isolated from Pogostemon cablin (Blanco) Benth. as novel influenza neuraminidase inhibitors.

BACKGROUND: Influenza is historically an ancient disease that causes annual epidemics and, at irregular intervals, pandemics. At present, the first-line drugs (oseltamivir and zanamivir) don't seem to be optimistic due to the spontaneously arising and spreading of oseltamivir resistance among influenza virus. Pogostemon cablin (Blanco) Benth. (P. cablin) is an important traditional Chinese medicine herb that has been widely used for treatment on common cold, nausea and fever. In our previous study, we have identified an extract derived from P. cablin as a novel selective neuraminidase (NA) inhibitor. RESULTS: A series of polyphenolic compounds were isolated from P. cablin for their potential ability to inhibit neuraminidase of influenza A virus. Two new octaketides (1, 2), together with other twenty compounds were isolated from P. cablin. These compounds showed better inhibitory activity against NA. The significant potent compounds of this series were compounds 2 (IC50 = 3.87 ± 0.19 µ mol/ml), 11, 12, 14, 15, 19 and 20 (IC50 was in 2.12 to 3.87 µ mol/ml), which were about fourfold to doubled less potent than zanamivir and could be used to design novel influenza NA inhibitors, especially compound 2, that exhibit increased activity based on these compounds. With the help of molecular docking, we had a preliminary understanding of the mechanism of the two new compounds (1-2)' NA inhibitory activity. CONCLUSIONS: Fractions 6 and polyphenolic compounds isolated from fractions 6 showed higher NA inhibition than that of the initial plant exacts. The findings of this study indicate that polyphenolic compounds and fractions 6 derived from P. cablin are potential NA inhibitors. This work is one of the evidence that P. cablin has better inhibitory activity against influenza, which not only enriches the compound library of P. cablin, but also facilitates further development and promises its therapeutic potential for the rising challenge of influenza diseases.

[A 1:1 matched case-control study on the interaction between HBV, HCV infection and DNA repair gene XPC Ala499Val, Lys939Gln for primary hepatocellular carcinoma].

OBJECTIVE: To evaluate the interaction between environmental factors, HBV/HCV infections and DNA repair gene XPC exon 8 Ala499Val, exon 15 Lys939Gln on related risks to primary hepatocellular carcinoma (PHC). METHODS: A 1:1 matched case-control study was conducted in Shunde city, Guangdong province. The genotypes of Ala499Val and Lys939Gln were detected by polymerase chain reaction restrictive fragment length polymorphism (PCR-RFLP) analysis, and gene-environment interactions were analyzed by conditional logistic regression. RESULTS: Among people infected by HBV with non- or at least one mutant gene of Ala499Val carriers, the risk of PHC significantly increased, with ORs as 3.768 (95%CI: 1.137 - 12.485) and 3.667(95%CI: 1.122 - 11.981) respectively. With non- or at least one mutant gene of Lys939Gln, the risk was increasing with ORs as 6.778 (95%CI: 2.025 - 22.688) and 3.152 (95%CI: 1.062 - 9.351) respectively. In those with HCV infection, non- or at least one mutant gene of Ala499Val might increase the risk with ORs as 2.955 (95%CI: 0.587 - 14.869), 1.085(95%CI: 0.307 - 3.839) respectively. However, when compared to the ones with no mutant gene of Lys939Gln among the same research subjects, those carrying at least one gene may decrease the risk, with OR lowered from 4.197 (95%CI: 0.870 - 20.243) to 0.887 (95%CI: 0.228 - 3.448). But the interactions between HBV infection, HCV infection and XPC genes were not statistically significant. CONCLUSION: Among people infected by HCV, the mutant gene of Ala499Val had the tendency to lower the risk of PHC, and the mutant gene of Lys939Gln also appeared the same in the population with either HBV infection or HCV infection in Shunde, Guangdong. Another study with large samples should be performed to analyze the interactions among environments-genes.