Plasma Concentrations of Contezolid and Its Efficacy and Safety in Elderly Patients with Multidrug-Resistant Tuberculosis and Renal Insufficiency.

As a new generation of oxazolidinone antibacterial drugs, contezolid has been shown to have comparable or even stronger activity than linezolid and has a low risk of adverse reactions such as bone marrow suppression toxicity. However, there are currently very few clinical reports and pharmacokinetic data of contezolid on the anti-tuberculosis therapy. Therefore, we report a case study of the pharmacokinetic study of contezolid in elderly patients with renal insufficiency and tuberculosis. The patient's condition improved after receiving an anti-tuberculosis regimen containing contezolid, with significant absorption of pleural effusion and lung plaques and nodules reduced. During the treatment, the patients' platelet and white blood cell levels fluctuated within normal ranges, but hemoglobin levels significantly decreased and did not recover after discontinuation of contezolid. The trough concentration of contezolid and the concentration at 2, 4, 6, and 10 h after administration were 1.27µg/mL, 3.88µg/mL, 6.32µg/mL, 8.99µg/mL, and 3.14µg/mL, respectively. The plasma concentrations of bedaquiline and cycloserine during the treatment were also monitored. This study demonstrated the efficacy and safety of contezolid in the treatment of multidrug-resistant tuberculosis and analyzed its pharmacokinetic changes in elderly patients with renal insufficiency, providing a reference for the clinical use of contezolid.

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.

Toxic epidermal necrolysis associated with chemoimmunotherapy for lymphoma: case report and literature review.

Aim: The emergence of antitumor immunotherapy has been beneficial for patients with tumors, but more attention should be paid to the toxic side effects of chemoimmunotherapy. Here we describe a patient with NK/T-cell lymphoma who developed toxic epidermal necrolysis (TEN) during treatment with a regimen consisting of sintilimab combined with pegaspargase, gemcitabine and oxaliplatin (P-GemOx). Case presentation: A patient received six cycles of P-GemOx chemotherapy as first-line treatment; 1 year later, he received the same dose of P-GemOx combined with sintilimab as chemoimmunotherapy due to recurrence of NK/T-cell lymphoma. He developed a massive rash that quickly developed into TEN after the fourth chemoimmunotherapy. Conclusion: Although rare, cases of fatal TEN caused by single-agent PD-1 inhibitor or gemcitabine have been reported. Careful attention to drug-related cutaneous toxicities is needed when these two agents are combined. This report highlights the significance of TEN as a rapid and serious adverse event induced by chemoimmunotherapy.

Immune checkpoint inhibitors that block the interaction of PD-1 with its ligand, PD-L1, have been increasingly used in cancer therapy. However, some rare side effects induced by these drugs, such as toxic epidermal necrolysis (TEN), can be extremely dangerous. Here we describe a patient with natural killer/T-cell lymphoma who developed TEN during treatment with a combination of sintilimab and pegaspargase/gemcitabine/oxaliplatin (P-GemOx). The patient received six cycles of P-GemOx chemotherapy as first-line treatment and showed no skin reactions during or after treatment. However, 1 year later, the patient received the same dose of P-GemOx combined with sintilimab as second-line treatment for recurrent natural killer/T-cell lymphoma and developed a massive rash that quickly developed into TEN after four cycles of chemoimmunotherapy. Cutaneous toxicities are some of the most prevalent immune-related adverse events, both with anti-PD-1 and anti-PD-L1 agents, which correspond to a class effect.

Anti-PD-1 Immunotherapy and Bee Venom for Relapsed and Refractory Liposarcoma: A Case Report.

Cancer immunotherapies, including immune checkpoint inhibitors, elicit long-term clinical responses but many cancer patients do not respond. Intensive efforts are therefore underway to identify additional immune pathways that may be modulated to enhance the efficacy of existing immunotherapies. Bee venom strongly stimulates the immune system, and is used as a complementary therapy to treat cancer pain in patients with advanced tumors in China. Bee venom contains several allergenic protease inhibitors and peptides. It triggers hypersensitivity reactions; that is, it is an immune system agonist. The generation of a spontaneous T cell response against tumor-associated antigens requires innate immune activation; this drives type I interferon production. We report a patient with a relapsed and refractory liposarcoma who had undergone several operations, chemotherapies, and radiotherapies. The tumor was large. The patient had attained the maximum radiation exposure dose. The tumor was resistant to chemotherapy and was infiltrating the pericardium, lungs, and diaphragm. The patient was a poor candidate for resection. He thus received apitherapy (a combination of bee venom and acupuncture) to control pain; then apatinib (an anti-angiogenic drug) was given to inhibit tumor growth but was terminated early because the patient could not tolerate the side effects. Subsequently, a programmed death 1 inhibitor was combined with apitherapy. Bee venom served as an innate immune system agonist promoting immune cell priming and recruitment in the tumor microenvironment. The patient was finally able to undergo radical liposarcoma resection, and no evidence of recurrence was found at re-examination 16 months after surgery.

Characterization of the complete chloroplast genome of Phragmites australis as a Chinese herb from Phragmites and Poaceae.

The root of Phragmites australis can often be used as the Chinese herb in China. In this paper, the complete chloroplast genome of P. australis was studied for more genetic information. The chloroplast genome was 137,561 bp in length as the circular and typical quadripartite structure, which contained a large single-copy region (LSC) of 82,328 bp, a small single-copy region (SSC) of 12,699 bp, and a pair of inverted-repeat regions (IRs) of 21,267 bp. The overall nucleotide composition of chloroplast genome is: 42,300 bp A (30.7%), 42,090 bp T (30.6%), 26,500 bp C (19.3%), 26,671 bp G (19.4%) and the total G + C content of 38.7%. However, 134 genes were found that included 87 protein-coding genes (PCGs), 39 transfer RNA (tRNAs), and 8 ribosome RNA (rRNAs). The Maximum-Likelihood (ML) method phylogenetic relationship with the reported chloroplast genomes showed that Phragmites australis is closely related to Setaria viridis and Setaria italic of the family Poaceae.