Lessons from Multiple Infections Such as Lymphoma Complicated with Pneumocystis Infection: A Case Report.

Background: Lymphoma is complicated by intricate infections, notably Pneumocystis jirovecii pneumonia (PJP), marked by rapid progression, respiratory failure, and high mortality. Rapid diagnosis of PJP and effective administration of the first-line treatment trimethoprim-sulfamethoxazole (TMP-SMX) are important. For patients intolerant to TMP-SMX, selecting appropriate alternatives is challenging, necessitating careful decisions to optimize diagnosis and treatment. We present a lymphoma case complicated by PJP, illustrating medication adjustment until a positive response was observed. Case Description: A 41-year-old male patient with lymphoma presented with a week-long history of fever, fatigue, cough, sputum, chest tightness, and exertional dyspnea, unresponsive to treatment. Routine laboratory examinations revealed no pathogenic bacteria. PJ and Mycobacterium tuberculosis (MTB) were detected in bronchoalveolar lavage fluid (BALF) using metagenomic next-generation sequencing (mNGS). On Day 1 of admission, meropenem, TMP-SMX, and rifampicin+isoniazid+levofloxacin were administered. However, the patient developed drug-induced hepatotoxicity and gastrointestinal adverse reactions after six days of treatment. After a multidisciplinary team discussion, anti-tuberculosis therapy was stopped because of insufficient evidence of tuberculosis infection. A reduced dose of TMP-SMX with micafungin was used for PJP; however, symptoms persisted and repeated computed tomography showed extensive deterioration of bilateral pulmonary plaques. The PJP regimen was modified to include a combination of TMP-SMX and caspofungin. Due to the high fever and elevated infection indices, the patient was treated with teicoplanin to enhance the anti-infection effects. By Day 13, the patient's temperature had normalized, and infection control was achieved by Day 30. CT revealed that the infection in both lung lobes fully resolved. Subsequently, lymphoma treatment commenced. Conclusion: BALF-NGS facilitates early and rapid diagnosis of PJP. mNGS reads of MTB bacillus <5 may indicate a bacterial carrier state, warranting other detection techniques to support it. There is insufficient evidence for using TMP-SMX with micafungin to treat PJP; however, TMP-SMX combined with caspofungin is suitable.

Mechanism of Hirudin-Mediated Inhibition of Proliferation in Ovarian Cancer Cells.

To investigate the inhibitory effect of hirudin on the cell proliferation of human ovarian cancer A2780 cells by preventing thrombin and its underlying molecular mechanism. Cell Counting Kit-8 (CCK-8) method was used to detect the effect of different concentrations of hirudin and thrombin on the cell proliferation of A2780 cells. PAR-1 wild-type overexpression plasmid was constructed utilizing enzyme digestion identification, and it was transferred to A2780 cells. Sequencing and Western blot were used to detect the changes in PAR-1 protein expression. Western blot detection of PKCα protein phosphorylation in A2780 cells was performed. We also implemented quantitative PCR to detect the mRNA expression levels of epithelial-mesenchymal transition (EMT)-related genes, CDH2, Snail, and Vimentin, in A2780 cells. 1 µg/ml hirudin treatment maximally inhibited the promotion of A2780 cell proliferation by thrombin. Hirudin inhibited the binding of thrombin to the N-terminus of PAR-1, hindered PKCα protein phosphorylation in A2780 cells, and downregulated the mRNA expression levels of CDH2, Snail, and Vimentin. In conclusion, hirudin inhibits the cell proliferation of ovarian cancer A2780 cells, and the underlying mechanism may be through downregulating the transcription level of EMT genes, CDH2, Snail, and Vimentin. This study indicates that hirudin may have a therapeutic potential as an anti-cancer agent for ovarian cancer.

Prognostic Nutritional Index Predicts Response and Prognosis in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Objective: To investigate the association between pretreatment prognostic nutritional index (PNI) and clinical survival outcomes for advanced-stage cancer patients treated with immune checkpoint inhibitors (ICIs). Methods: We conducted a comprehensive literature search to identify eligible studies concerning the relationship between pretreatment PNI and survival outcomes in advanced cancer patients treated with ICIs. Published data were extracted and pooled odds ratio (pOR) for objective response rate (ORR), disease control rate (DCR), and pooled hazard ratio (pHR) for overall survival (OS), progressive-free survival (PFS), along with 95% confidence intervals (95% CIs) were calculated. Results: Twelve studies with 1,359 participants were included in our study. A higher level of PNI indicated a greater ORR (pOR = 2.17, 95% CI = 1.52-3.10) and favorable DCR (pOR = 2.48, 95% CI = 1.87-3.29). Low PNI was associated with a shorter OS (pHR = 2.24, 95% CI = 1.57-3.20) and unfavorable PFS (pHR = 1.61, 95% CI = 1.37-1.88). Conclusion: Low PNI might be an effective biomarker of poor tumor response and adverse prognosis of advanced cancer patients with ICIs. Further studies are needed to verify the prognostic value of PNI in clinical practice.