Successful treatment of linezolid-induced severe lactic acidosis with continuous venovenous hemodiafiltration: A case report

Linezolid is an oxazolidinone antibiotic. Linezolid-associated lactic acidosis has been reported in 6.8% of linezolid-treated patients. Lactic acidosis is associated with poor clinical outcomes, with high blood lactate levels resulting in organ dysfunction and mortality. This case report describes the development of lactic acidosis in a 64-year-old Chinese woman who had received 33 days of treatment with antituberculosis drugs and 28 days of treatment with oral linezolid for tuberculous meningitis. Severe lactic acidosis was reversed by withdrawing antituberculosis drugs and using continuous venovenous hemodiafiltration (CVVH). When the patient's condition was stable, she was transferred to the infectious disease department, and antituberculosis drugs, with the exception of linezolid, were reintroduced. This did not result in recurrence of lactic acidosis. The causal relationship between lactic acidosis and linezolid was categorized as ‘probable’ on the Adverse Drug Reaction Probability Scale. This case demonstrates that CVVH has potential as an alternative to discontinuation of linezolid alone for rapid reversal of linezolid-associated severe lactic acidosis.     

经鼻高流量氧气湿化治疗老年慢性阻塞性肺疾病急性加重合并呼吸衰竭的可行性研究

ObjectiveTo investigate the feasibility of transnasal heated humidified high flow nasal cannula oxygen therapy (HFNC) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with respiratory failure in elderly patients. MethodsA total of 176 elderly patients with AECOPD complicated with respiratory failure who were hospitalized at Peking University Shougang Hospital from December 2016 to January 2022 were enrolled, including 82 patients in an HFNC group and 94 patients in an NPPV group. After treatment, pulse oxygen saturation (SPO₂), arterial partial pressure of carbon dioxide (PaCO₂), oxygenation index (OI), respiratory rate (RR), heart rate (HR), mean arterial pressure (MAP), comfort score, discharge rate, rate of endotracheal intubation, rate of transfer to intensive care unit (ICU), and mortality were compared between the two groups. The independent sample t-test was used for comparison between the two groups. Statistical data are expressed in percentage or number of cases and the χ² test was used for their comparisons. ResultsThe SPO₂ values at 30 min, 1 h, and 6 h were significantly higher in the HFNC group than in the NPPV group (t=-2.049,-2.618, and -3.314, P=0.043, 0.010, and 0.001, respectively). SPO₂ before discharge was significantly lower than that of the NPPV group (t=2.162, P=0.033), but OI at each time point and before discharge had no statistical significance (P＞0.05). MAP at 6 h was significantly higher in the HFNC group than in the NPPV group (t=-2.209, P=0.029), but within the normal range. HRs at 2 h and 3 h in the HFNC group were significantly higher than those of the NPPV group (t=-2.199 and -2.336, P=0.030 and 0.021, respectively). There were no significant differences in RR, HR, or MAP between the two groups at other time points and before discharge (P＞0.05). There was no significant difference in PaCO2 between the two groups (P＞0.05). Comfort score in the HFNC group was significantly higher than that of the NPPV group (t=-46.807, P＜0.001). There were no significant differences in discharge rate, ICU transfer rate, endotracheal intubation rate, and mortality between the two groups (P＞0.05). ConclusionHFNC is as effective as NPPV in treating elderly patients with AECOPD complicated with type Ⅰ or mild type Ⅱ respiratory failure, and HFNC is more comfortable than NPPV.     

The effect of hypoxia on photodynamic therapy with 5-aminolevulinic acid in malignant gliomas

BackgroundGlioblastoma (GBM) is a high-grade, poor prognosis tumor that is resistant to standard treatment. The presence of a small number of glioma stem cells (GSCs) surviving in the harsh microenvironment is responsible for their refractoriness. This study aimed to investigate the effect of a hypoxic environment on the sensitivity of GSCs to photodynamic therapy with 5-aminolevulinic acid (ALA-PDT).Materials and methodsSix human GSC lines, Mesenchymal types HGG13, HGG30, HGG1123, and Proneural types HGG146, HGG157, HGG528, were divided into two groups: normoxia (O₂ 21%)-cultured cells (Normoxia-GSCs), and hypoxia (O₂ 5%)-cultured cells (Hypoxia-GSCs). To compare the effects of different oxygen partial pressures on photoporphyrin Ⅸ (PpⅨ) biosynthetic activity, PpⅨ biosynthetic enzyme and transporter expression levels were examined by qRT-PCR; the intracellular PpⅨ concentration was determined using flow cytometry. Additionally, the sensitivity of these two groups of cells to ALA-PDT was evaluated in vitro.ResultsHypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert PpⅨ to heme, compared with Normoxia-GSCs. Flow cytometry revealed that the accumulation of PpⅨ in Hypoxia-GSCs reduced upon incubation with ALA. However, Hypoxia-GSCs showed less reduction in sensitivity to ALA-PDT than Normoxia-GSCs.ConclusionHypoxia-GSCs had lower intracellular PpⅨ accumulation than Normoxia-GSCs due to increased gene expression of FECH, and that their sensitivity to ALA-PDT was reduced less, despite accumulating lower concentrations of PpⅨ. ALA-PDT is a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration.     

Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review of Economic Evaluations

The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources.     

Interventions in the diagnosis and adoption of pacemaker therapy in sinus node dysfunction patients: Results from the IMPROVE Brady study

AimsIMPROVE Brady assessed whether a process improvement intervention could increase adoption of guideline-based therapy in sinus node dysfunction (SND) patients.Methods/Results: IMPROVE Brady was a sequential, prospective, quality improvement initiative conducted in India and Bangladesh. Patients with symptomatic bradycardia were enrolled. In Phase I, physicians assessed and treated patients per standard care. Phase II began after implementing educational materials for physicians and patients. Primary objectives were to evaluate the impact of the intervention on SND diagnosis and pacemaker (PPM) implant. SF-12 quality of life (QoL) and Zarit burden surveys were collected pre- and post-PPM implant.A total of 978 patients were enrolled (57.7 ± 14.8 years, 75% male), 508 in Phase I and 470 in Phase II. The diagnosis of SND and implantation of PPM increased significantly from Phase I to Phase II (72% vs. 87%, P < 0.001 and 17% vs. 32%, P < 0.001, respectively). Pacemaker implantation was not feasible in 41% of patients due to insurance/cost barriers which was unaltered by the intervention. Both patient QoL and caregiver burden improved at 6-months post-PPM implant (P < 0.001).ConclusionsA process improvement initiative conducted at centers across India and Bangladesh significantly increased the diagnosis of SND and subsequent treatment with PPM therapy despite the socio-economic constraints.     

Efficacy of photobiomodulation in the management of tinnitus: A systematic review of randomized control trials

There is a controversy in regards to the efficacy of photobiomodulation (PBM) in the management of tinnitus. The aim was to systematically review randomized controlled trials (RCTs) that assessed the efficacy of PBM (low-level laser therapy) in the management of tinnitus. The focused question was “Is PBM effective in the management of tinnitus?”. Indexed databases were searched up to and including June 2020 using different combinations of the following key words: (a) laser; (b) diode; (c) low-level laser therapy; (d) photobiomodulation; (e) tinnitus; (f) medium-level laser; (g) photo-biomodulation; and (h) low-power laser; and RCTs performed on humans were included. Letters to the editor; case reports/series; commentaries; experimental studies and historic reviews were excluded. The risk of bias was assessed using the modified cochrane collaboration tool. The format of the current systematic review was personalized to summarize the appropriate information. Ten RCTs (2 single-blinded and 8 double-blinded) were included. One study reported 30% and 100% resolution of tinnitus using diode and Neodymium-doped Yttrium Aluminum Garnet lasers; respectively. One study reported that PBM was effective in relieving tinnitus for up to 3 months. Eight studies reported that PBM was ineffective in the management of chronic tinnitus. The risk of bias was high; medium and low in 4; 5 and 1 studies; respectively. The effectiveness of PBM in the management of tinnitus remains debatable. Further power-adjusted and well-designed RCTs with long-term follow-up are needed.     

Long-term prevention of bladder cancer progression by alpha1-oleate alone or in combination with chemotherapy

Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of nonmuscle invasive bladder cancer. Our study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least 4 weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and in vitro, alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer.