黒崎 史朗

BACKGROUND: Amikacin liposome inhalation suspension (ALIS) has been used in several countries including Japan for refractory Mycobacterium avium complex pulmonary disease (MAC-PD). Although its efficacy and adverse events have been reported, factors that limit optimal treatment outcomes in real-world practice are not fully understood. Therefore, we aimed to provide practical considerations for optimizing ALIS therapy by identifying factors associated with culture conversion. METHODS: We retrospectively reviewed the medical records of patients with refractory MAC-PD who were treated with ALIS at a single center between October 2021 and June 2025. Patients treated for ≥ 6 months were included and categorized into culture conversion and non-conversion groups. Clinical characteristics and treatment-related factors were analyzed. Follow-up continued until December 2025. RESULTS: During the study period, 30 patients with refractory MAC-PD were treated with ALIS. Three patients who discontinued ALIS within 6 months were excluded from further analysis because of MAC-related death (n = 1) or severe ALIS-related adverse events (n = 2). Consequently, 27 patients were included in the analysis. The median age was 69.9 years, and the median duration of ALIS therapy was 14.6 months. The sputum culture conversion rate was 51.8% (14/27; 95% CI, 34.0-69.3%). Pulmonary fungal disease was identified in 7 patients (25.9%), including newly diagnosed cases during ALIS therapy; however, pulmonary fungal disease was not significantly associated with culture conversion. Cavitary lesions and prior aminoglycoside use were significantly associated with non-conversion. In addition, inappropriate ALIS administration, including prolonged intermittent use and inadequate nebulizer handset replacement, was significantly associated with non-conversion. Dysphonia was the most frequent adverse event and occasionally led to prolonged intermittent use of ALIS. ALIS-related lung abnormalities on computed tomography (CT) scans were observed in 21 of 26 patients. CONCLUSIONS: Cavitary lesions, prior aminoglycoside use, and inappropriate ALIS administration were associated with culture non-conversion. Several factors related to ALIS administration and inhalation management may be modifiable, and appropriate patient education, regular reassessment of inhalation practices, and careful monitoring of ALIS administration may help optimize treatment outcomes.

BACKGROUND: Central pain, characterized by neuropathic pain, can manifest due to injury to the superior spinothalamic tract. The brainstem includes sensory and motor pathways as well as nuclei of the cranial nerves, and therefore cancer metastasis in the region requires early intervention. Although stereotactic radiosurgery (SRS) is commonly employed for the treatment of brain metastasis, it poses risks of late complications like radiation necrosis (RN). RN exacerbates the progression of brain lesions within the irradiated area, and in the brainstem, it can damage multiple nerves, including the superior spinothalamic tract. Central neuropathic pain is often intractable and empirically managed with a combination of conventional drugs, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants. However, their efficacy is often limited, leading to a decline in performance status (PS) and quality of life (QOL). CASE PRESENTATION: We present the case of a 53-year-old man diagnosed with stage IV lung cancer, referred to our palliative care team for managing severe central pain resulting from SRS-related RN in the pons. Despite administration of opioids, including oxycodone and hydromorphone, and adjuvant analgesics, the patient continued to require frequent use of immediate-release opioids. The addition of methadone alone proved successful in achieving optimal pain control. CONCLUSIONS: Provided that RN in the brainstem can lead to intractable neuropathic pain, it is advisable to avoid SRS for brainstem metastasis when possible. Add-on methadone should be considered as a viable pain management medication for patients experiencing unresolved central pain.

Tuberculous meningitis (TBM) is a rare disease in low-incidence countries like Japan, where general physicians have fewer experience with TBM. Despite its proper treatment and early improvement of the condition, TBM often causes paradoxical reactions (PRs), which can lead to severe complications such as stroke. As PRs in the brain are difficult to detect without regular neuroimaging surveillance and have a later onset than in other organs, delayed treatment can be fatal. We report a case of a 54-year-old, human immunodeficiency virus (HIV)-negative man who presented with TBM and miliary tuberculosis (TB) in an unconscious state. Standard anti-tuberculous therapy with adjunctive systemic high-dose dexamethasone brought rapid clinical and microbiological improvement, which allowed the dexamethasone to be tapered. However, he developed cerebral infarction with left hemiplegia due to a TBM-related PR five months after admission. Therefore, the initial high-dose dexamethasone was again added to the anti-tuberculous drugs, achieving the significant effects on the PR-related lesions. Anti-tuberculous drugs had been administered for 3 years and the dexamethasone was carefully tapered. Nevertheless, enlargement of PR-related lesions in the brain recurred 5 years later. Accordingly, the dose of corticosteroid was again increased, resulting in resolving the lesions. It is important to note that severe TBM may cause prolonged PRs, which require a long-term neuroimaging follow-up and anti-inflammatory drugs for the successful management of the TBM-related PR.