Food group intakes and high-sensitivity C-reactive protein among community-dwelling Japanese adults: a cross-sectional study.

OBJECTIVE: Healthy dietary patterns have been linked to lower levels of chronic inflammation. The present study aimed to investigate the associations between food group intakes and high-sensitivity C-reactive protein (hsCRP) among community-dwelling adults. DESIGN: Cross-sectional. SETTING: Three areas in Japan (Shiga, Fukuoka, or Kyushu and Okinawa). PARTICIPANTS: The present analysis included 13 648 participants (5126 males and 8522 females; age range, 35-69 years) who had been enrolled in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Food group intakes were estimated using a FFQ. Multiple linear regression was used to examine associations between the quartiles of each energy-adjusted food group intake and log-transformed hsCRP. RESULTS: The following concentration ratios of hsCRP after comparing the highest and lowest quartiles of food group intake were significant: in males, 1·12 (95 % CI 1·02, 1·22) for processed meat, 1·13 (95 % CI 1·03, 1·24) for fish and 0·83 (95 % CI 0·76, 0·90) for nuts; in females, 0·89 (95 % CI 0·81, 0·97) for bread, 1·11 (95 % CI 1·03, 1·19) for processed meat, 0·86 (95 % CI 0·80, 0·92) for vegetables, 1·19 (95 % CI 1·11, 1·29) for fruit, 0·90 (95 % CI 0·84, 0·97) for nuts and 0·88 (95 % CI 0·82, 0·95) for green tea. CONCLUSIONS: Processed meat and nut intakes were associated with higher and lower hsCRP levels, respectively, in both sexes. However, for several food groups, including fish and fruit, previous findings from dietary pattern analyses were not supported by the present analyses at the food group level.

An Infant With COVID-19 Presenting With a Bulging Fontanel: A Case Report and Literature Review.

A bulging fontanel is a sign of elevated intracranial pressure, which can be caused by diseases with intracranial fluid retention or swelling of the cerebral parenchyma. We experienced a case of an infant with a typical course of mild coronavirus disease 2019 (COVID-19) but with a bulging fontanel as a finding at presentation. The patient, a three-month-old boy with no underlying conditions, presented to the emergency clinic with fever, vomiting, and loss of appetite. Due to the absence of crying and the bulging fontanel, he was referred to our hospital with suspected bacterial meningitis. The diameter of the anterior fontanel was 2.5 cm, as measured by the Popich and Smith method. He showed no signs of consciousness impairment and appeared to be as active as usual. Computed tomography revealed a bulging fontanel. Cerebrospinal fluid examination showed no elevated cell counts, and cultures were negative. Accordingly, bacterial meningitis was ruled out. The fever resolved on the day after admission, and the patient was discharged on the third day after admission in good general condition. When an infant diagnosed with COVID-19 presents with a bulging fontanel, it is important to be aware of its low specificity and excessive antibiotic treatment should be reconsidered.

Perineoplasty for anal incontinence after obstetric anal sphincter injury repair: a case report.

BACKGROUND: The rectal and vaginal walls are typically sutured if severe perineal lacerations with rectal mucosal damage occur during vaginal delivery. In case of anal incontinence after the repair, re-suturing of the anal sphincter muscle is standard procedure. However, this procedure may not result in sufficient improvement of function. CASE PRESENTATION: A 41-year-old woman underwent suture repair of the vaginal and rectal walls for fourth-degree perineal laceration at delivery. She was referred to our department after complaining of flatus and fecal incontinence. Her Wexner score was 15 points. Examination revealed decreased anal tonus and weak contractions on the ventral side. We diagnosed anal incontinence due to sphincter dysfunction after repair of a perineal laceration at delivery. We subsequently performed sphincter re-suturing with perineoplasty to restructure the perineal body by suturing the fascia located lateral to the perineal body and running in a ventral-dorsal direction, which filled the space between the anus and vagina and increased anal tonus. One month after surgery, the symptoms of anal incontinence disappeared (the Wexner score lowered to 0 points), and the anorectal manometry values increased compared to the preoperative values. According to recent reports on the anatomy of the female perineal region, bulbospongiosus muscle in women does not move toward the midline to attach to the perineal body, as has been previously believed. Instead, it attaches to the ipsilateral surface of the external anal sphincter. We consider the fascia lateral to the perineal body to be the fascia of the bulbospongiosus muscle. CONCLUSIONS: In a case of postpartum anal incontinence due to sphincter dysfunction after repair of severe perineal laceration, perineoplasty with re-suturing an anal sphincter muscle resulted in improvement in anal sphincter function. Compared to conventional simple suture repair of the rectal wall only, this surgical technique may improve sphincter function to a greater degree.

Daratumumab­resistant multiple myeloma with extramedullary disease successfully treated with combination elotuzumab, pomalidomide and dexamethasone: A case report.

Despite the emergence of monoclonal antibodies, the prognosis of patients with multiple myeloma (MM) with extramedullary disease remains poor. The present report describes a rare case of daratumumab-refractory MM that was successfully treated with elotuzumab, pomalidomide and dexamethasone. A 66-year-old male patient diagnosed with MM was treated with bortezomib, lenalidomide and dexamethasone, followed by high-dose chemotherapy and autologous stem cell transplantation. Thereafter, the patient was treated with lenalidomide and dexamethasone as maintenance therapy. This was changed to daratumumab, bortezomib and dexamethasone when new paraskeletal lesions were identified, resulting in marked tumor shrinkage. After 15 months, an increase in serum monoclonal protein levels, development of a skeletal lesion in the right second rib and extramedullary disease of the right thoracic mediastinal lymph nodes were noted. Treatment with elotuzumab, pomalidomide and dexamethasone (EPd) resulted in expeditious symptomatic improvement and regression of the lesions. Notably, during daratumumab, bortezomib and dexamethasone treatment, lymphocyte counts gradually increased to a level at which elotuzumab was sufficiently effective. EPd might be a promising strategy for the treatment of patients with relapsed extramedullary MM while on daratumumab treatment.

Predictors of stricture after non-circumferential endoscopic submucosal dissection of the esophagus and single-dose triamcinolone injection immediately after the procedure.

BACKGROUND AND AIMS: Local triamcinolone (TA) injection is widely used to prevent stricture formation after endoscopic submucosal dissection (ESD). However, stricture develops in up to 45% of patients despite this prophylactic measure. We therefore conducted a single-center prospective study to identify predictors of stricture after esophageal ESD and local TA injection. METHODS: Patients who underwent esophageal ESD and local TA injection and who were comprehensively assessed for lesion- and ESD-related factors were included in the study. Multivariate analyses were conducted to identify the predictors of stricture. RESULTS: A total of 203 patients were included in the analysis. Multivariate analysis identified residual mucosal width ≤5 mm (odds ratio [OR], 29.0; P < .0001) or 6 to 10 mm (OR, 3.7; P = .04), history of chemoradiotherapy (OR, 5.1; P = .045), and tumor in the cervical or upper thoracic esophagus (OR, 3.8; P = .018) as independent predictors of stricture. Based on the ORs of the predictors, patients were stratified into 2 groups according to stricture risk: patients in the high-risk group (residual mucosal width ≤5 mm or 6-10 mm with another predictor) had a stricture rate of 52.5% (31 of 59 cases), and patients in the low-risk group (residual mucosal width ≥11 mm or 6-10 mm without other predictors) had a stricture rate of 6.3% (9 of 144 cases). CONCLUSIONS: We identified predictors of stricture after ESD and local TA injection. Local TA injection prevented stricture formation after ESD in low-risk patients but was not sufficient to prevent stricture in high-risk patients. Additional interventions should thus be considered in high-risk patients. (University Hospital Medical Network Clinical Trials Registry number: UMIN 000028894.).

[A Case of Postoperative Anastomotic Leakage with Septic Shock after Esophageal Cancer Surgery Treated by Two Stage Operation Using Ileocolic Reconstruction].

The patient was a 60s male. He underwent esophagectomy and gastric tube reconstruction for Barrett's esophageal cancer( pT3N1M0, pStage Ⅲ). Postoperatively, anastomotic leakage and mediastinitis resulted in septic shock. On the 8th day after first surgery, he transferred to our hospital. At the time of admission, qSOFA was 3 points. We judged to be difficult to treat with conservative treatment. Emergency right thoracotomy drainage underwent with resection of the esophagogastric anastomosis and cervical esophagostomy construction. He was discharged on the 55th postoperative day with home enteral nutrition. He underwent presternal ileocolic reconstruction on the 97th day after right thoracotomy drainage. On the 19th day after reconstruction, oral intake was started. The general condition is good without recurrence, and oral intake is sufficient at 1 year after reconstruction. We report a case of anastomotic leakage with septic shock after esophageal cancer surgery successfully treated by 2 stage ileocolic reconstruction.

[Clinical Outcomes of Treatment for Esophageal Cancer Recurrence after Surgery].

Many cases with esophageal cancer recurrence have worse clinical survival. Treatment with immune checkpoint inhibitor (ICI)has been reported to result in significantly longer overall survival. We investigated the clinical outcomes in 30 patients with esophageal cancer recurrence who underwent neoadjuvant chemotherapy followed by surgery, chemotherapy, and chemoradiotherapy. Results: Of the 30 patients investigated, 25 were men. Median patient age was 70(range 52-84)years. The recurrence sites are as follows: 17 in locoregional, 5 in lung, 2 in bone, 3 in liver, and 5 in others. The overall survival in early recurrence(within 6 months after surgery)cases and multiple recurrence cases were significantly shorter than that in later recurrence(>6 months after surgery)and single recurrence(p=0.031, p<0.01). Of 30 recurrence cases, 9 cases (30%)achieved complete response(CR). Five of CR cases were treated by chemotherapy with ICI. In esophageal cancer recurrence, treatment with ICI showed good response and survival benefit. In future, the indication of ICI is evaluated for adjuvant therapy after surgery.

[Acquired thrombotic thrombocytopenic purpura following COVID-19].

COVID-19 often contributes to thrombus formation in microvessels, resulting in damaged vital organs. In this study, we report a case of COVID-19 associated with acquired thrombotic thrombocytopenic purpura (TTP). A 44-year-old man with a history of systemic lupus erythematosus presented with COVID-19 and concomitant hemolytic anemia and a marked thrombocytopenia. The patient was diagnosed with acquired TTP because ADAMTS13 inhibitor was detected and ADAMTS13 activity below the sensitivity level. The patient developed agitated neuropsychiatric symptoms, such as aphasia, disorientation, and delirium, which improved after a plasma exchange, prednisolone, and rituximab administration. Only a few reports have revealed COVID-19 with TTP, and this is the first case in Japan. Although acquired TTP rarely develops, it is an important complication of COVID-19, and thus, it should be promptly diagnosed and treated as soon as possible.

Anti-inflammatory effects of ruxolitinib on chronic neutrophilic leukemia harboring CSF3R-T618I mutation with bilateral renal abscesses.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by sustained mature neutrophilic leukocytosis. Recently, presence of colony-stimulating factor 3 receptor (CSF3R) mutations has been added to the diagnostic criteria for CNL. Anti-inflammatory effects of the JAK1/2 inhibitor ruxolitinib relieve constitutional symptoms associated with MPN, such as fatigue, night sweats, and fever. We present a case of CNL harboring CSF3R-T618I mutation exacerbated by concomitant bilateral renal abscesses, which was refractory to antibiotics, at the time of initial diagnosis. In this case, ruxolitinib rapidly improved not only CNL but the infection, due to its anti-inflammatory potency.

Impact of endoscopic surveillance on mortality of metachronous esophageal and head and neck cancer after esophageal endoscopic resection.

BACKGROUND AND AIM: As more superficial esophageal cancer (EC) patients are being treated with endoscopic resection (ER), it is important to understand the outcomes, including survival data, of patients who develop metachronous EC and head and neck cancer (HNC). We aimed to evaluate the long-term surveillance and survival outcomes of metachronous EC and HNC after esophageal ER. METHODS: This study included 627 patients who underwent ER of superficial esophageal squamous cell carcinoma from 2008 to 2016 and were generally followed by annual or biannual esophagogastroduodenoscopy up to 2019 at Osaka International Cancer Institute. Data on metachronous cancer development and causes of death were collected from an integrated database of hospital-based cancer registry and Vital Statistics of Japan. RESULTS: During a median (range) follow-up period of 67.4 (3.8-142.7) months, 230 patients (36.7%) developed 500 metachronous ECs and 126 patients (20.1%) developed 239 metachronous HNCs, post-ER of index EC. The 3-year, 5-year, and 7-year cumulative incidences were 25.8%, 36.0%, and 43.6% for metachronous EC and 10.9%, 16.0%, and 26.9% for metachronous HNC, respectively. No patients died of metachronous EC, and only seven patients (1.1%) died of metachronous HNC. The 3-year, 5-year, and 7-year disease-specific survival rates were 99.8%, 99.6%, and 98.6%, respectively. CONCLUSIONS: The incidences of metachronous EC and HNC increase with time over 5 years after esophageal ER; therefore, surveillance endoscopy should be continued over 5 years. Endoscopic surveillance is useful for survivors after esophageal ER given the high incidence and extremely low mortality of metachronous EC and HNC.

Clinical features of superficial esophagus squamous cell carcinoma according to alcohol-degrading enzyme ADH1B and ALDH2 genotypes.

BACKGROUND: Inactivated alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are related to esophageal carcinogenesis. We aimed to clarify the clinical features associated with the alcohol-degrading enzyme genotypes, ADH1B and ALDH2. We also investigated the risk factors for metachronous esophageal squamous cell carcinoma (ESCC) and head and neck SCC (HNSCC). METHODS: We conducted a single-center, retrospective study including patients with ESCC treated by endoscopic resection. Patients were recruited between October 2020 and September 2021. Buccal mucosal swabs were obtained from them to analyze the genetic polymorphisms affecting ADH (ADH1B) and ALDH (ALDH2) activity. Patients were categorized into three groups: both inactivated = double-inactivated group; inactivated ADH1B or ALDH2 = single-inactivated group; and both activated = activated group. RESULTS: Among the 297 enrolled patients, patients in the double-inactivated group were significantly younger (P < 0.001) and 60% of them were ≤ 50 years old. This group also had more ESCCs located in the upper esophagus (P < 0.001) and more simultaneous multiple ESCCs (P = 0.044). More than half of the patients had multiple Lugol-voiding lesions (LVLs) (P < 0.001) and heavy alcohol consumers (P = 0.012). Metachronous ESCC and HNSCC were more common in the double-inactivated group (P < 0.001, P = 0.001). Multivariate analysis identified located in the upper esophagus, multiple LVLs and history of HNSCC as risk factors for metachronous ESCC. CONCLUSIONS: Activation patterns of alcohol-metabolizing enzymes were related to age at ESCC onset, lesion location, and metachronous ESCC and HNSCC. Different approaches to the prophylaxis and treatment of esophageal cancer should be considered, depending on the enzyme activity pattern.

[Extranodal NK/T cell lymphoma, nasal type with local recurrence in the contralateral nasal cavity 15 years after initial sequential chemoradiotherapy].

A 72-year-old woman was diagnosed with extranodal NK/T cell lymphoma of the right nasal cavity and received sequential radiochemotherapy comprising focal radiotherapy and THP-COP chemotherapy. Showed a complete tumor response to the treatment; however, the tumor recurred in the contralateral right nasal cavity 15 years after the initial treatment. This was judged to be a marginal recurrence in the radiation field. After four cycles of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy, a second complete response was achieved. It is possible that another recurrence occurs in the future, and if the lesion is localized at the time of recurrence, it may be possible to control the disease again. Careful follow-up is considered necessary.

Sterilizing Ability of High-Voltage Pulsed Discharge Plasma with Cavitation for Microorganisms Including Radio-Resistant Bacterium in Water.

There are various purification methods have been developed and applied to industrial wastewater with contaminated microorganisms. We previously reported that high-voltage pulsed discharge plasma with cavitation effectively kills Escherichia coli cells. We attempted to expand the application of this disinfection method by using microorganisms such as Bacillus subtilis, Deinococcus radiodurans, and Schizosaccharomyces pombe. These microbial cells were treated with the discharge plasma, and the cell viability, DNA damage, and morphological changes were analyzed to evaluate the bactericidal effect. Interestingly, D. radiodurans, a radio-resistant bacterium showed relatively high sensitivity to the discharge plasma. On the other hand, B. subtilis and S. pombe showed the resistance, showing both sporogenesis. The amount of DNA damage in the treated cells corresponded to the cell viability, but most of the treated cells did not show any morphological changes.

[Listeria meningitis during daratumumab/bortezomib/dexamethasone therapy in a patient with multiple myeloma].

An 88-year-old woman was diagnosed with multiple myeloma received third-line chemotherapy, including DBd (daratumumab [DARA], bortezomib, and dexamethasone [Dex]), and the myeloma was in remission. Sulfamethoxazole/trimethoprim (ST) prophylaxis was discontinued because the dose of Dex was reduced to 20 mg every 4 weeks after 21 cycles of DBd. After 28 cycles of DBd, altered consciousness with fever ensued, and she was referred to the emergency department where Listeria monocytogenes (LM) meningitis was diagnosed. CD38 inactivation is associated with increased LM susceptibility. In patients on Dara-based chemotherapy, antibiotic prophylaxis should be considered using ST, which has activity against Listeria.

Associations of breastfeeding history with metabolic syndrome and cardiovascular risk factors in community-dwelling parous women: The Japan Multi-Institutional Collaborative Cohort Study.

OBJECTIVE: The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the associations depend on age. METHODS: The present cross-sectional study included 11,118 women, aged 35-69 years. Participants' longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis. RESULTS: Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged <55 years, an inverse dose-response relationship was found between the number of breastfed children and the prevalence of metabolic syndrome; multivariable-adjusted odds ratios for 1, 2, 3, and ≥4 breastfed children were 0.60 (95% confidence interval [CI]: 0.31 to 1.17), 0.50 (95% CI: 0.29 to 0.87), 0.44 (95% CI: 0.24 to 0.84), and 0.35 (95% CI: 0.14 to 0.89), respectively. The longest and total breastfeeding durations of longer than 0 months were also associated with lower odds of metabolic syndrome relative to no breastfeeding history in participants aged <55 years. In contrast, all measures of breastfeeding history were not significantly associated with metabolic syndrome and cardiovascular risk factors in participants aged ≥55 years old. CONCLUSIONS: Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women.

[Short- and Long-Term Effects of Palliative Stoma Creation on Quality of Life].

Palliative stoma creation for malignant gastrointestinal obstruction improves quality of life, and advances in chemotherapy have resulted in long-term survival after stoma creation. We reviewed early and late complications in 24 patients treated with palliative stoma creation. Results: 14 men(58%)and 10 women(42%)had a median age of 60 years. Twenty-three patients(96%)were able to eat more than a porridge diet postoperatively, and the median The ColoRectal Obstruction Scoring System(CROSS)improved from 1(0-3)to 4(2-4)(p<0.001). Postoperative complications(all Clavien-Dindo grades)were observed in 10 patients(42%), with a longer postoperative hospital stay in the complication group than in the group without complication(median 34 days: 17 days, p=0.026). When divided into long-term survivors and short- term survivors based on a median overall survival of 101 days, more stoma prolapse occurred in the long-term survivors(4 cases 33% vs 0 cases 0%, p=0.028), one of which required repair surgery. Conclusion: Long-term survivors after exploratory stoma creation are more likely to develop a stoma prolapse. Careful surgical manipulation and postoperative support system including stoma care are important.

[Successful treatment with imatinib for a patient with myeloid neoplasms with eosinophilia and abnormalities of PDGFRB due to t (5;14)(q33;q22)].

A 50-year old man with a 1-year history of eosinophilia presented with an eosinophil count exceeding 13,800/mm3 in the peripheral blood at the first visit. Bone marrow examination revealed that eosinophils accounted for 30% of the nucleated cell count, and G-band karyotyping analysis detected t (5;14)(q33;q22). Using peripheral blood FISH test, he was found to have platelet-derived growth factor receptor ß (PDGFRB) locus rearrangement at 5q32-33. The level of eosinophils in the peripheral blood reduced markedly 3 days after the initiation of Imatinib mesylate, 400 mg daily. This treatment was administered for 2 years, after which the peripheral blood FISH test was negative for PDGFRB. In this disease, although most cases are with t (5;12), those with t (5;14) are relatively rare, and the long-term course of this translocation is unknown.

Anti-Glypican-1 Antibody-drug Conjugate as Potential Therapy Against Tumor Cells and Tumor Vasculature for Glypican-1-Positive Cholangiocarcinoma.

Cholangiocarcinoma is a highly malignant cancer. Many patients need systemic chemotherapy to prevent tumor development and recurrence; however, their prognosis is poor due to the lack of effective therapy. Therefore, a new treatment option is urgently required. We recently identified glypican-1 (GPC1) as a novel cancer antigen of esophageal squamous cell carcinoma. We also demonstrated the efficacy and safety of GPC1-targeted ADC (GPC1-ADC) conjugating anti-GPC1 mAb possessing high internalization activity with monomethyl auristatin F (MMAF), which is a potent tubulin polymerizing inhibitor. In this study, we confirmed that GPC1 was highly expressed in cholangiocarcinoma cells and tissues. IHC analysis of 49 extrahepatic cholangiocarcinoma patient tumor specimens revealed high expression of GPC1 in 47% of patients. These patients demonstrated significantly poorer prognosis compared with the low-expression group in terms of disease-free survival and overall survival (P < 0.05). GPC1 was also expressed in tumor vessels of cholangiocarcinoma, but not on the vessels of nontumor tissues. MMAF-conjugated GPC1-ADC showed potent tumor growth inhibition against GPC1-positive cholangiocarcinoma cells in vitro and in vivo In a GPC1 knockout xenograft model, GPC1-ADC partially inhibited tumor growth. Vascular endothelial cells in tumor tissues of GPC1-negative xenograft mice expressed GPC1 and were arrested in the G2-M phase of cell cycle by GPC1-ADC. GPC1-ADC exhibits direct as well as indirect antitumor effects via inhibition of tumor angiogenesis. Our preclinical data highlight GPC1-ADC as a promising therapy for GPC1-positive cholangiocarcinoma.

Extracting clinical terms from radiology reports with deep learning.

Extracting clinical terms from free-text format radiology reports is a first important step toward their secondary use. However, there is no general consensus on the kind of terms to be extracted. In this paper, we propose an information model comprising three types of clinical entities: observations, clinical findings, and modifiers. Furthermore, to determine its applicability for in-house radiology reports, we extracted clinical terms with state-of-the-art deep learning models and compared the results. We trained and evaluated models using 540 in-house chest computed tomography (CT) reports annotated by multiple medical experts. Two deep learning models were compared, and the effect of pre-training was explored. To investigate the generalizability of the model, we evaluated the use of other institutional chest CT reports. The micro F1-score of our best performance model using in-house and external datasets were 95.36% and 94.62%, respectively. Our results indicated that entities defined in our information model were suitable for extracting clinical terms from radiology reports, and the model was sufficiently generalizable to be used with dataset from other institutions.

Osimertinib is associated with reversible and dose-independent cancer therapy-related cardiac dysfunction.

INTRODUCTION: The use of osimertinib is associated with the risk of cancer therapy-related cardiac dysfunction (CTRCD) for EGFR-mutated non-small cell lung cancer (NSCLC) patients. In this study, we aimed to clarify the clinical features of patients with CTRCD associated with osimertinib. METHODS: A total of 183 cases of advanced EGFR-mutated NSCLC who received osimertinib monotherapy from January 2014 to December 2019 were evaluated. Longitudinal changes in LVEF were evaluated in 58 patients by serial echocardiography before and after osimertinib administration. RESULTS: Of 58 patients, 16 patients (8.7%) had decreased LVEF of 10 units or more and 8 patients (4.4%) met the CTRCD criteria. Overall, LVEF significantly decreased after osimertinib treatment from a mean value of 69% (range, 52-82%) at baseline to 66% (26-75%) (p < 0.001). During osimertinib treatment, LVEF remained low but did not decline any further. Discontinuation, dose reduction, or switching to another EGFR tyrosine kinase inhibitors resulted in recovery in 6 out of 8 CTRCD patients. Multivariate analysis showed that history of heart disease was a significant predictor of CTRCD (ORR, 4.97; 95% confidence interval [CI], 1.26-19.6; P = 0.022). CONCLUSIONS: Osimertinib was associated with the risk of CTRCD, which is dose-independent and reversible with drug withdrawal.