Organizing Pneumonia With Diffuse Alveolar Hemorrhage Induced by the Kampo Medicine Choreito.

Kampo medicine, a traditional Japanese herbal medicine, is covered by the Japanese National Health Insurance and prescribed for various purposes. While relatively safe with few adverse effects, it may potentially cause severe adverse effects, such as lung injury. Herein, we describe the case of a 61-year-old Japanese woman with choreito-induced lung injury that manifested as organizing pneumonia (OP) with diffuse alveolar hemorrhage (DAH). She was referred to our department due to multiple abnormal opacities detected on annual chest radiography. Chest computed tomography (CT) revealed multiple nodules in bilateral lungs. Bloody bronchoalveolar lavage fluid was obtained from the left lingular lobe, appearing nearly normal, while a transbronchial lung biopsy from a subpleural nodule in the left lower lobe was pathologically consistent with OP. The drug lymphocyte stimulation test result was positive for choreito, which the patient had regularly consumed for 6 - 7 months to treat hematuria. Consequently, a diagnosis of choreito-induced OP and DAH was made. Owing to the discontinuation of choreito alone and without the introduction of systemic steroid therapy, the multiple nodules shrank and eventually disappeared on follow-up chest CT. Regardless of the type of crude drug used in Kampo medicine, clinicians must always be careful for potential lung injury, which may present as OP with DAH.

Pneumonitis During Durvalumab Consolidation Therapy Affects Survival in Stage III NSCLC.

Introduction: Durvalumab consolidation therapy is the standard of care after concurrent chemoradiotherapy (CRT) for stage III NSCLC. Immune-related pneumonitis during durvalumab treatment is potentially fatal; however, information is lacking regarding the impact of pneumonitis on patient survival. This study investigates the effect of pulmonary and nonpulmonary immune-related adverse events (irAEs) on the efficacy of durvalumab treatment in patients with stage III NSCLC. Methods: We retrospectively assessed 158 patients who received durvalumab after CRT at nine Japanese institutions between July 2018 and March 2020. Survival outcomes were compared between patients who developed pneumonitis with those who developed irAEs other than pneumonitis. Patients who survived for less than 3 months were excluded to reduce immortal time bias. Results: Among 158 evaluated patients, 76 (48%) experienced grade less than or equal to one irAEs, whereas 82 (52%) experienced grade greater than or equal to two irAEs. Among the patients with grade greater than or equal to two irAEs, those with grade greater than or equal to two pneumonitis (n = 55) were compared with those with grade greater than or equal to two irAEs other than pneumonitis (n = 27). Patients with grade greater than or equal to two pneumonitis exhibited a significantly worse overall survival than those with grade greater than or equal to two irAEs that excluded pneumonitis. Multivariate analysis revealed that grade greater than or equal to two pneumonitis (hazard ratio = 3.71; 95% confidence interval, 1.85-7.45; p < 0.001) and squamous histology (hazard ratio = 2.64; 95% confidence interval, 1.29-5.42; p = 0.008) were independently associated with worse overall survival. Conclusions: After minimizing immortal time bias, pneumonitis grade two or greater and squamous histology were poor prognostic factors in patients who received consolidation durvalumab after CRT.

Elevation of serum lactate dehydrogenase during methylprednisolone pulse therapy as a predictor of high mortality in acute respiratory failure: A single-center, retrospective study.

Background: Corticosteroids are common treatments in certain diseases that cause acute respiratory failure (ARF) and are sometimes administered empirically for patients with critical ARF. Associations between changes in clinical parameters following initiation of steroid pulse therapy and mortality in patients with ARF have not been previously investigated. Methods: This was a single-center and retrospective cohort study. Parameters on the day of methylprednisolone pulse therapy initiation (day 1) and the day following the end of methylprednisolone therapy (day 4) in patients who were admitted because of ARF and underwent methylprednisolone pulse therapy between October 2008 and July 2021 were reviewed. Results: A total of 98 patients were included in our analysis, and 45 (46%) died at our hospital. Change in lactate dehydrogenase (LDH) from day 1 to day 4 (ΔLDH) was significantly higher in the in-hospital death group than in the survival group (-68 IU/L in the survival group versus 46 IU/L in the in-hospital death group, p < 0.01). Multivariate logistic analyses showed that age >75 years old (odds ratio (OR), 3.88; 95% confidence interval (CI), 1.38-10.9; p < 0.01), previously diagnosed interstitial lung disease (OR, 3.43; 95% CI, 1.10-10.7; p = 0.03), ΔLDH > 0 (OR, 6.47; 95% CI, 2.30-18.2; p < 0.01), and ΔSequential Organ Failure Assessment score > 0 (OR, 3.06; 95% CI, 1.10-8.51; p = 0.03) were significantly associated with in-hospital mortality. Conclusions: This study showed that elevation of serum LDH level during methylprednisolone pulse therapy was a predictive factor for high in-hospital mortality in patients with ARF.

A Case of Radiation-Associated Vertebral Compression Fracture Mimicking Solitary Bone Metastasis of Lung Cancer.

Radiation therapy plays an important role in the treatment of lung cancer. Although adverse effects of radiation are well known, they are sometimes difficult to be diagnosed. We report a case of a radiation-associated vertebral compression fracture which mimicked bone metastasis of lung cancer. The patient was a 57-year-old man diagnosed with lung squamous cell carcinoma (cT1aN2M0, c-stage IIIA). He received concurrent chemoradiotherapy (CRT) in combination with 6 weeks of weekly carboplatin plus paclitaxel and thoracic radiation of 60 Gy/30 fractions, followed by bi-weekly durvalumab for 12 months. On the last day of the 12-month durvalumab regimen, he complained of backache. Magnetic resonance imaging showed compression fracture of the seventh thoracic vertebra with the spinal cord compressed, and fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography demonstrated weak focal uptake only at the seventh thoracic vertebra. Although the fracture had been suspected to be bone metastasis, surgical biopsy revealed no evidence of malignancy. Since the seventh thoracic vertebra was included in the irradiation area, the patient was diagnosed with a radiation-associated fracture. Dual-energy X-ray absorptiometry of the lumbar vertebrae (L2 - 4) after the surgery revealed osteopenia. In conclusion, we successfully diagnosed the radiation-associated vertebral fracture caused by radical CRT. The fracture mimicked bone metastasis in preoperative imaging tests. Thus, surgical biopsy was useful for diagnosis.

Long-Term Responders to Erlotinib for Pulmonary Adenocarcinoma With Wild-Type Epidermal Growth Factor Receptor: Two Case Reports and a Single-Institutional Retrospective Study.

Erlotinib is an oral and reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and is now used exclusively to non-small cell lung carcinoma (NSCLC) harboring mutated EGFR. However, there was historically a transient period when erlotinib was widely used regardless of EGFR mutation status. We report two cases with adenocarcinoma and wild-type EGFR status, which responded to erlotinib for unusual long time. We also retrospectively analyzed patients with adenocarcinoma and wild-type EGFR mutation status who had received erlotinib-containing regimen in our hospital. A 60-year-old woman received the second-line and tri-weekly regimen of pemetrexed (500 mg/m2 on day 1) and intermittent erlotinib (150 mg on days 2 - 16). Pemetexed was discontinued 18 months after the initiation of this regimen, but erlotinib was continued for more than 11 years. This chemotherapy successfully reduced her brain metastasis and prevented recurrence. A 58-year-old man received erlotinib monotherapy as the third-line regimen, by which multiple brain metastases disappeared. Although we tried stopping erlotinib 9 years after the initiation of erlotinib, a solitary metastasis appeared in the brain 3 months after the discontinuation of erlotinib. Between December 2007 and October 2015, 39 patients with wild-type EGFR status initiated erlotinib-containing regimens at our hospital. The response rate, progression-free survival and overall survival were 17.9% (95% confidence interval (CI): 7.5-33.5%), 2.7 months (95% CI: 1.8 - 5.0 months) and 10.3 months (95% CI: 5.0 - 15.7 months), respectively. We reported two long-term responders and survivors to erlotinib for more than 9 years, which was much longer than patients with adenocarcinoma and wild-type EGFR mutation status who had received erlotinib-containing regimen in our hospital.

Durvalumab for Extensive-Stage of Small-Cell Lung Cancer With Lambert-Eaton Myasthenic Syndrome.

Durvalumab is an immune checkpoint inhibitor (ICI) of anti-programmed cell death protein 1 ligand antibody. ICI-combined chemotherapy has recently become a standard regimen for extensive-stage of small-cell lung cancer (ES-SCLC). SCLC is well known to be the most likely tumor associated with Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune disease of a neuromuscular junction disorder. Although LEMS has been reported to be induced by ICI as immune-mediated adverse events, it remains unknown whether ICI can deteriorate preexisting paraneoplastic syndrome (PNS) of LEMS. Our rare case was successfully treated by durvalumab plus chemotherapy without exacerbation of preexisting PNS of LEMS. We report a 62-year-old female with ES-SCLC and preexisting PNS of LEMS. She started carboplatin-etoposide in combination with durvalumab. This immunotherapy achieved nearly complete response. However, multiple brain metastases were found after two courses of maintenance durvalumab. Her symptoms and physical examinations of LEMS improved despite of no significant change in compound muscle action potential amplitude in the nerve conduction study. The titer of anti-P/Q-type voltage-gated calcium channel (VGCC) antibody decreased from 1,419.2 to 263.5 pmol/L during the immunotherapy. In conclusion, ICI in combination with platinum doublet chemotherapy is still challenging but may be a treatment option for ES-SCLC patients complicated with PNS of LEMS.

Standard versus low-dose nab-paclitaxel in previously treated patients with advanced non-small cell lung cancer: A randomized phase II trial (JMTO LC14-01).

BACKGROUND: Nab-paclitaxel (nab-PTX) has better transfer to tumor tissue than cremophor-based paclitaxel. It suggests that the optimum dose of nab-PTX might be lower than the dose and schedule that is widely used. We designed a randomized phase II trial to examine the clinical utility and safety of nab-PTX in patients with previously treated advanced non-small cell lung cancer (NSCLC). METHODS: Patients were randomly allocated (1:1) to receive nab-PTX monotherapy at 100 mg/m2 (group A) or 70 mg/m2 (group B). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs). RESULTS: Finally, 81 patients were randomized. Similar results were observed in both groups for PFS (3.75 vs. 3.71 months), OS (13.50 vs. 16.13 months), or ORR (20.5% vs. 23.1%). The incidences of grade 3 or worse AEs were 57.5% in group A and 41.5% in group B. The proportion of serious side effects was 10.0% in group A and 4.9% in group B. CONCLUSION: Both standard dose and low dose of nab-PTX monotherapy are active for previously treated NSCLC patients with better safety profile. Therefore, nab-PTX 70 mg/m2 dose and schedule in the trial would be a reasonable option.

Sarcoid-Like Granulomatosis of the Lung Related to Durvalumab After Chemoradiation for Pulmonary Squamous Cell Carcinoma.

Sarcoid-like granulomatosis is a unique immune-related adverse event (irAE) in cancer patients treated with immune checkpoint inhibitors (ICIs). This irAE is infrequent, reported to range from 2% to 22.2% of melanoma treated with ICI. In a case of granulomatosis localized in the lung, it is difficult to differentiate granulomatosis from cancer progression or metastases. Herein, we report a case of ICI-induced sarcoid-like granulomatosis of the lung, which was confusable with localized recurrence of the primary lung cancer. A 56-year-old woman with c-stage IIIA of pulmonary squamous cell carcinoma in the right lower lobe received chemo-radiotherapy with two courses of cisplatin and vinorelbine and concurrent thoracic irradiation, followed by 1-year durvalumab consolidation therapy. The tumor in the right S6 grew and presented abnormal uptake by fluorodeoxyglucose positron emission tomography (FDG-PET), 1.5 years after durvalumab. Neither computed tomography (CT) nor FDG-PET found mediastinal and distant metastases. She underwent right lower lobe lobectomy. Histopathologically, the tumor and sampled lymph nodes contained no residue of carcinoma cells but presented diffuse epithelioid granuloma with infiltration of inflammatory cells, partial necrotic lesions and many multinucleated giant cells. In immunohistochemical stains, CD3+ and CD8+ T cells predominantly infiltrated, while there were few CD4+ T cells and a small number of CD20+ B cells. We followed her without steroid and other immunosuppressant drug. We should pay attention to the development of sarcoid-like granulomatosis as a rare irAE, which is difficult to be differentiated from cancer progression.

Lenvatinib-refractory thymic mucinous carcinoma with PIK3CA mutation.

Mucinous adenocarcinoma, a very rare type of thymic carcinoma, is aggressive and has a poor prognosis. The optimal treatment for advanced thymic mucinous adenocarcinoma has not yet been established because of its rarity. An oral multi-tyrosine kinase inhibitor, lenvatinib, was approved for treatment of thymic carcinoma in March 2021 in Japan. However, to the best of our knowledge, there are no published reports concerning lenvatinib for thymic mucinous adenocarcinoma. Herein, we report a 39-year-old woman who presented with a 70 mm multilocular cystic tumor in her left anterior mediastinum and a massive pericardial effusion. We diagnosed a Masaoka stage IVb thymic mucinous adenocarcinoma with multiple metastases to the liver and bones, and pericardial dissemination on the basis of the pathologic findings on examination of a video-assisted thoracoscopic tumor biopsy and radiological examinations. She received paclitaxel-carboplatin-based chemotherapy, but developed a left cerebellar metastasis. Second-line chemotherapy with lenvatinib failed to suppress the tumor. She died of cancer progression 5 months after presentation. Here, we report what we believe to be the first case of a thymic mucinous adenocarcinoma treated with lenvatinib. Our patient's thymic mucinous adenocarcinoma was refractory to both cytotoxic chemotherapy and lenvatinib. Using next-generation sequencing, we identified phosphatidylinositol 3-kinase catalytic subunit alpha mutation in the tumor. We suspected an association between this mutation and resistance to lenvatinib. We therefore recommend performing next-generation sequencing when considering introduction of lenvatinib for thymic mucinous adenocarcinoma. A surgical procedure may be necessary for accurate diagnosis and genetic analysis of this histological tumor type.

Rituximab for the Treatment of Anti-glomerular Basement Membrane Disease with Isolated Diffuse Alveolar Hemorrhage.

Anti-glomerular basement membrane (GBM) disease with isolated diffuse alveolar hemorrhage (DAH) is rare. We herein report a 91-year-old man admitted with hypoxia and diagnosed with anti-GBM disease with DAH based on positive bronchoalveolar lavage and serum antibody test results. There was no renal involvement. Although remission was achieved using glucocorticoids and plasmapheresis, the patient experienced DAH relapse one week after the last plasmapheresis. Rituximab 375 mg/m2 was administered 4 times weekly; thereafter, DAH relapse was not observed, and the glucocorticoid dosage was tapered. Rituximab was thus effective in treating anti-GBM disease with isolated DAH in an extremely elderly patient.

Successful Dasatinib Treatment of Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinoma and BCR-ABL1-Positive Chronic Myeloid Leukemia: A Case Report.

Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI), inhibits multiple kinase pathways and is a promising anti-tumor agent for various solid tumors, including lung cancer. Herein, we report a patient with coexisting epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma and BCR-ABL1-positive chronic myeloid leukemia (CML). The patient received afatinib for a postoperative intrapulmonary recurrence of lung adenocarcinoma harboring EGFR exon 19 deletion. Tumor reduction was achieved with afatinib; however, dose reduction was required because of grade 2 diarrhea and skin toxicity. The reduced dose maintained a partial response. Thirty-one months after introduction of afatinib, he was diagnosed as having BCR-ABL1-positive CML and nilotinib was added to his treatment regimen. However, the combination of nilotinib and afatinib aggravated his diarrhea, prompting discontinuation of afatinib. Because nilotinib does not have sufficient anti-tumor efficacy for CML, dasatinib was substituted for nilotinib. Thirty-five months after introduction of dasatinib, bosutinib was substituted for dasatinib because of uncontrollable pleural effusions. Dasatinib achieved 31- and 35-month progression-free survivals for CML and EGFR-mutant lung adenocarcinoma, respectively. Dasatinib is thus a therapeutic option for coexisting EGFR-mutant lung adenocarcinoma and BCR-ABL1-positive CML when TKI combination therapy is contraindicated by severe adverse events. In our patient, adding nilotinib to afatinib led to severe diarrhea. When administering TKI combination therapy, drug-drug interactions should be considered.

Cerebral Infarction Caused by Trousseau's Syndrome Associated With Lung Cancer.

Background: Lung cancer is one of the common cancers that can cause Trousseau's syndrome. However, there are few reports of cerebral infarction due to Trousseau's syndrome associated with lung cancer. The aim of this study is to investigate the clinical features of lung cancer-related cerebral infarction and effective management practice. Methods: Japanese patients diagnosed with Trousseau's syndrome-related cerebral infarction associated with lung cancer between August 2012 and November 2021 in our hospital were retrospectively enrolled. Clinical data, treatment, and outcomes of the patients were collected. Results: Ten patients were enrolled. The median age was 65 years (range: 43 - 84 years). All patients had advanced lung cancer. The histological types were adenocarcinoma (n = 8), pleomorphic carcinoma (n = 1), and small cell lung cancer (n = 1). Recurrent cerebral infarction occurred in six patients. Among four patients who had continued heparin since the initial infarction, recurrence occurred in one. D-dimer was high in all 10 patients at the initial cerebral infarction. D-dimer level at the time of recurrent cerebral infarctions was higher than that at the first cerebral infarctions. Since performance status declined in nine patients, one patient continued anticancer drugs after cerebral infarction. Four patients died within 100 days of the onset of cerebral infarction. Conclusions: Cerebral infarction of lung cancer-related Trousseau's syndrome has poor prognosis. Heparin may be effective in controlling the condition. In addition, D-dimer may serve as a marker of cancer-related thrombosis.

High neutrophils and low lymphocytes percentages in bronchoalveolar lavage fluid are prognostic factors of higher in-hospital mortality in diffuse alveolar hemorrhage.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a syndrome resulting from bleeding in the microcirculation of the lung, with a poor prognosis. The study aim was to identify prognostic factors of DAH, especially bronchoalveolar lavage fluids (BALF) cell pattern. METHODS: We conducted a single-center retrospective cohort study of patients diagnosed as having DAH and hospitalized at our hospital between October 2008 and July 2020. We performed univariate logistic regressions to identify variables associated with in-hospital death. RESULTS: Sixty-eight patients were included in our analysis. In-hospital mortality was 26.5%. Variables associated with in-hospital death were neutrophils percentage in BALF ≥ 44.5% [Odds Ratio (OR) 16.0, 95% confidence interval (CI) 4.33-58.9)], lymphocytes percentage in BALF < 14% (OR 7.44, 95% CI 2.11-26.2), idiopathic DAH (OR 0.31, 95% CI 0.10-0.95), oxygen flow ≥ 4L/min (OR 3.90, 95% CI 1.20-12.6), and estimated glomerular filtration rate < 60 mL/min (OR 5.00, 95%CI 1.29-19.4). CONCLUSIONS: High neutrophils and low lymphocytes percentages in BALF were associated with poor prognosis.

Pembrolizumab-Induced Meningoencephalitis: A Brain Autopsy Case.

Encephalitis is very rare, but often fatal immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs). A 65-year-old Japanese woman was admitted to our hospital because of general fatigue, chillness and high-grade fever for 4 days, 8 months after the initiation of the first-line pembrolizumab monotherapy for metastatic pulmonary adenocarcinoma. On the hospital day 3, she suddenly presented delirium and uncontrollable impaired consciousness. Although the magnetic resonance imaging (MRI) did not suggest a diagnosis of encephalitis and meningitis, the spinal fluid showed abnormally elevated levels of protein (317.6 mg/L) and cell count (197 cells/µL) with increased mononuclear cells (93%). An empirical and intravenous administration of acyclovir in doses of 10 mg/kg body weight every 8 h and steroid pulse therapy in dose of 1 g/body/day from the hospital day 5 until her death failed to improve her conditions. She died on the hospital day 8. The postmortem autopsy showed viable cancer cells in the metastatic tumor in the left occipital lobe and in the spinal fluids. However, many inflammatory cells infiltration in the meninges and perivascular cuffing were prominent especially in the brain stem and medial part of the temporal lobe. Infiltrating lymphocytes in the meninges and parenchyma of the brain stem were mainly composed of cluster of differentiation (CD)8-positive lymphocytes. For irAE encephalitis, early recognition of early signs and symptoms and subsequent early therapeutic intervention are necessary. It is important for oncologists to keep in mind of the possible adverse effects of immunotherapies on the nervous system.

Pulmonary Adenosquamous Cell Carcinoma With Systemic Lymphadenopathy due to Immunoglobulin G4-Related Disease: A Case Report.

A 75-year-old man with diabetes mellitus showed elevated C-reactive protein (CRP) level at his regular visit. Computed tomography scan showed a lung tumor in his left lower lobe and systemic lymphadenopathy including abdominal lymph nodes. The patient was diagnosed as primary pulmonary squamous cell carcinoma with systemic lymph node metastasis. Thereafter, unexpected steroid pulse therapy for accidental acute exacerbation of interstitial pneumonia rapidly shrank lymphadenopathy. At this time, we also found elevated serum immunoglobulin G4 (IgG4) level (385 mg/dL). Considering these findings, we doubted the lymph nodes metastases at the initial staging, and then corrected cancer-staging (C-staging) from inferior vena cava (IVC) to inferior abdomen (IA). In addition, during the steroid tapering, sudden onset and uncontrollable left pneumothorax required surgical approach. Curative-intent left lower lobectomy with lymphadenectomy was performed for the lung cancer. Pathological findings revealed coexistence of adenosquamous carcinoma and infiltration of IgG4-positive plasma cells in the resected mediastinal lymph node. We detected 384 IgG4-positive cells per high power field. IgG4/IgG-positive cell ratio was 54%. Based on these findings, the diagnosis of IgG4-related disease with primary adenosquamous carcinoma (p-stage IIIA) was confirmed. The patient died 24 days after surgery because of another acute exacerbation of interstitial pneumonia. Our case alerts oncologists to IgG4-related disease as a possible underlying comorbidity which may confuse pretreatment clinical stage.

Osimertinib-Induced Unilateral Diffuse Alveolar Hemorrhage in a Patient With Pulmonary Adenocarcinoma.

A 70-year-old man with lung adenocarcinoma was admitted to our hospital due to progressive dyspnea, 4 months after osimertinib initiation. His chest radiograph and computed tomography revealed ground-glass opacities and consolidations dominantly in the upper left lung. He took neither antiplatelet nor anticoagulation agent. No abnormality in coagulation was detected. Bronchoalveolar lavage fluid (BALF) became serially and increasingly hemorrhagic, and confirmed the diagnosis of alveolar hemorrhage. After steroid pulse therapy and withdrawal of osimertinib, his condition gradually improved, accompanied by regression of ground-glass opacities and consolidations. Osimertinib causes not only interstitial pneumonia but also alveolar hemorrhage. The consolidations may spread not bilaterally, but be localized unilaterally. We have to keep this rare adverse event in mind, and consider immediate withdrawal of osimertinib and treatment with steroid. Increased lymphocytes in the BALF may be a potential indicator of sensitivity to steroid and favorable prognosis in diffuse alveolar hemorrhage.

Transformation From Adenocarcinoma to Pleomorphic Carcinoma as an Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

Pulmonary pleomorphic carcinoma is a very rare histological type of primary lung cancer, and usually provides aggressive clinical courses. A 65-year-old Japanese woman was diagnosed by transbronchial biopsy of the primary tumor as c-stage IV (cT4N3M1b) of adenocarcinoma harboring L858R point mutation in the exon 21 of epidermal growth factor receptor (EGFR). She received EGFR tyrosine kinase inhibitors (TKIs) (gefitinib and erlotinib) and subsequently cytotoxic chemotherapies. Gefitinib achieved partial response, but was switched to erlotinib due to elevated serum aspartate transaminase. After resistance to EGFR-TKIs, the second transbronchial re-biopsy revealed pulmonary pleomorphic carcinoma. Both carcinomatous and sarcomatous components retained the L858R mutation, but did not acquire T790M mutation. This case suggested that the histological transformation to pulmonary pleomorphic carcinoma may be one of mechanisms of drug resistance to EGFR-TKIs.

Effect of home-based rehabilitation of purposeful activity-based electrical stimulation therapy for chronic stroke survivors: a crossover randomized controlled trial.

BACKGROUND: In this trial we combined the effect of purposeful activity and electrical stimulation therapy (PA-EST) to promote transition of severely hemiparetic upper limb to auxiliary upper limb in chronic stroke survivors in a single-case study. OBJECTIVE: The purpose of this study was to examine the effect of PA-EST on the upper limb motor function in a crossover randomized controlled trial. METHODS: The study included eight stroke survivors (age: 63.1±10.9 years) who were receiving home-based visiting occupational therapy. The average time since stroke onset was 8.8±5.6 years. All participants had severely hemiparetic upper limb, with the Fugl-Meyer Assessment upper extremity (FMA-U) score of 21.3±8.5. Participants were randomly assigned to group A or B. Group A received PA-EST for 3 months (phase 1), followed by standard stretching and exercise for 3 months (phase 2), whereas group B had the inverse order of treatments. To avoid carry-over effect, 1-month washout period was provided between the phase 1 and 2. Two-way analysis of variance (ANOVA) with repeated measures was used for the analysis. The primary outcome was FMA-U, and the secondary outcomes were, Motor Activity Log (MAL; amount of use [AOU] and quality of movement [QOM]), and Goal attainment scale-light (GAS-light). RESULTS: Repeated measures-ANOVA revealed a significant interaction between type of intervention and time for FMA-U (F = 16.303, P = 0.005), MAL AOU (F = 7.966, P = 0.026) and QOM (F = 6.408, P = 0.039), and GAS-light (F = 6.905, P = 0.034), where PA-EST was associated with significantly improved motor function and goal achievement compared with standard stretching. CONCLUSIONS: The PA-EST may have greater effects than stretch/exercise in the recovery of hand function as reflected in FMA-U, MAL, and GAS-light. Our results suggest that PA-EST is an important and useful home-based rehabilitation program for promoting the use of the severely hemiparetic upper limb in chronic stroke survivors.

Secondary organizing pneumonia after coronavirus disease 2019: Two cases.

Coronavirus disease 2019 (COVID-19) has been reported to induce persistent symptoms even after an acute phase. However, the pathophysiology and treatment of this condition have been unclear. We report two patients who recovered from COVID-19, but presented persistent respiratory symptoms. Their respiratory conditions deteriorated, and computed tomography showed remaining ground glass opacities and consolidations. The pathological findings of transbronchial lung biopsy corresponded to organizing pneumonia. We diagnosed them with secondary organizing pneumonia after COVID-19. Subsequently, we administered systemic corticosteroids. Their symptoms, oxygenations, radiologic findings, and pulmonary functions rapidly improved after the treatment of corticosteroids. The two cases showed that secondary organizing pneumonia may be a cause of persistent respiratory failure after COVID-19. In this condition, corticosteroids may be effective.

Osimertinib-induced cardiac failure with QT prolongation and torsade de pointes in a patient with advanced pulmonary adenocarcinoma.

Osimertinib-induced cardiotoxicity is a well-known but rare disorder. An 84-year-old woman was diagnosed with recurrence of lung adenocarcinoma showing an epidermal growth factor receptor mutation of exon 19 deletion, which was initially treated by curative-intent thoracic radiotherapy 4 years prior. She started taking osimertinib (80 mg/day). She had no history of heart disease and showed no signs of cardiac problems. However, 2 months later she presented with symptoms of cardiac failure and QT prolongation on electrocardiogram. Cardiac enzyme levels were not elevated and coronary computed tomography angiography showed no significant stenosis. On admission, sudden-onset torsade de pointes required electrocardioversion. Thus, drug-induced cardiac failure was strongly suspected and we stopped osimertinib therapy. Cardiac function and the electrocardiogram abnormality improved. To our knowledge, this is the third case of coincidence of cardiac failure and QT prolongation and the second case of sudden-onset torsade de pointes associated with osimertinib treatment. In our case, osimertinib-induced cardiac failure with QT prolongation was recovered by stopping the drug treatment. The potential for cardiotoxicity should be considered with osimertinib treatment.