Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors.

Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung cancer. Herein, we report the case of a 70-year-old man with resectable colorectal adenocarcinoma who underwent surgery followed by adjuvant therapy. He relapsed with multiple liver metastases and received standard chemotherapy until his disease became refractory. Comprehensive genomic profiling of his postoperative colorectal cancer tissue revealed EGFR-KDD. He was treated with an EGFR tyrosine kinase inhibitor (TKI), afatinib and achieved a partial response (- 55%) after 8 weeks; however, he developed massive malignant ascites after 13 weeks. Osimertinib, another EGFR-TKI, controlled his tumors for 9 months. Patient-derived cancer organoids from his malignant ascites confirmed sensitivity to EGFR-TKIs. The findings suggest that EGFR-TKIs can be a potential treatment option for this molecular subgroup.

Nationwide survey of the secondary findings in cancer genomic profiling: survey including liquid biopsy.

We surveyed the status of the secondary finding (SF) disclosure in comprehensive genome profiling (CGP) in 2020. The situation has changed: increase in the number of hospitals that provide CGP, an update to the Comprehensive Tumor Genomic Profiling: Materials for Review of Secondary Findings (CTGPMRSF), and the addition of a liquid biopsy test, FoundationOne® Liquid CDx (F1L). Moreover, the actual situation was unclear because the 2020 survey did not include all designated and cooperative hospitals. Herein, we conducted a questionnaire survey of all designated-core, designated, and cooperative hospitals to identify the current status and challenges concerning SF in the CGP in 2022. A total of 82.1% of the hospitals responded and 77.7% of the response was from cooperative hospitals. Approximately 80% of the hospitals used CTGPMRSF. SF disclosure, confirmatory test implementation, and SF confirmation rates were 12.4%, 31.6%, and 46.6% for FoundationOne® CDx (F1CDx), respectively, and 6.8%, 31.8%, and 70.7% for F1L, respectively. The implementation rate of the confirmatory test was substantially higher in hospitals with genetic experts and in hospitals that could conduct confirmatory tests on the same day. Our survey provides insight into how SF is handled in Japan. The percentage of cases leading to confirmatory tests has gradually increased, although challenges such as insurance coverage limitations and varied understanding of SF among patients and healthcare providers persist. With the increasing use of whole-genome analysis, our findings will provide valuable insights into establishing an effective SF disclosure system.

Neoadjuvant Treatment with Changes in Chemotherapy Regimens According to Carbohydrate Antigen 19-9 Level for Resectable/Borderline Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: The response of carbohydrate antigen (CA) 19-9 to neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) may contribute to outcomes. This study aimed to investigate the effect of changes in NAT regimens based on CA19-9 level. METHODS: This single-center retrospective study included patients with resectable/borderline resectable (R/BR)-PDAC undergoing NAT from 2008 to 2022. A CA19-9 level lower than 150 IU/mL after NAT was the criterion for resection. If the level did not decrease, the chemotherapy regimen was changed to satisfy the criterion. The patient cohort was divided into group A (satisfied criterion without changing chemotherapy), group B (did not receive chemotherapy change, could not satisfy the criterion), group C (received chemotherapy change, satisfied the criterion), and group D (received chemotherapy change, could not satisfy the criterion). RESULTS: The study cohort included 283 patients. After first-line chemotherapy, 112 (39.6%) patients did not satisfy the criterion (groups B [n = 64], C [n = 32], and D [n = 16]). Of the 283 patients, 48 (17%) received a chemotherapy change (groups C and D). The patients in groups C and D showed significantly better overall survival (OS, 35.9 months) than the group B patients (25.7 months) (P = 0.035). The OS of the group C patients (63.8 months) was similar to the OS of the group A patients (n = 171: 56.3 months; P = 0.430). Multivariate analysis of the patients in groups B, C, and D identified chemotherapy change as an independent prognostic factor for OS and progression-free survival. CONCLUSION: Changing the chemotherapy targeting the CA19-9 level can improve the outcome of R/BR-PDAC patients with poor biologic response to first-line NAT.

Protocol digest of a randomized phase III trial comparing S-1-based chemoradiotherapy with/without nivolumab for unresectable locally advanced or borderline resectable pancreatic cancer: JCOG1908E (PENETRATE).

Pancreatic cancer remains a highly lethal disease with a 5-year survival proportion of <10%. Chemoradiotherapy is a treatment option for unresectable locally advanced (UR-LA) or borderline resectable (BR) pancreatic cancer, but its efficacy is not sufficient. Induction of the synergistic effect of irradiation and immune checkpoint inhibitors can be an attractive strategy. An open-label randomized phase III trial has been conducted since October 2020 to confirm the superiority of nivolumab plus S-1-based chemoradiotherapy over S-1-based chemoradiotherapy alone in patients with UR-LA or BR pancreatic cancer. A total of 216 patients will be enrolled in 14 institutions within 3.5 years. The primary endpoint of the safety run-in part is dose-limiting toxicity, and that of the phase III part is overall survival. This trial was registered at the Japan Registry of Clinical Trials as jRCT2080225361 (https://jrct.niph.go.jp/latest-detail/jRCT2080225361).

Association of Calf Circumference, Hand Grip Strength, and Physical Performance with Serious Adverse Events in Patients with Sub-Acute Stroke Hospitalized for Rehabilitation: An Observational Study.

OBJECTIVE: To determine whether calf circumference (CC), hand grip strength (HGS), and physical performance are linked to the incidence of serious adverse events (SAEs) in patients with sub-acute stroke. DESIGN: Retrospective cohort study. SETTING: Single rehabilitation hospital. PARTICIPANTS: Stroke patients admitted for rehabilitation hospital. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The incidence of SAEs, such as death, cardiovascular events including recurrent stroke, and conditions requiring transfer to another hospital for specialized care or immediate treatment for an acute illness during hospitalization. RESULTS: A total of 341 patients (median age: 74 years) participated in this study, with 232 patients (68%) exhibiting low physical performance. In the adjusted model, low physical performance was significantly associated with SAEs (HR = 3.01, 95% CI = 1.04-8.68, p = 0.042). However, low CC (HR = 1.60, 95% CI = 0.76-3.38, p = 0.219) and low HGS (HR = 0.98, 95% CI = 0.39-2.42, p = 0.960) did not show an independent association. CONCLUSION: Low physical performance was independently associated with the occurrence of SAEs during hospitalization for rehabilitation in patients with sub-acute stroke.

[Current Status and Issues of Companion Diagnostics in Cancer Genomic Medicine].

As of December 2023, there are 5 types of cancer gene panel tests covered by public insurance in Japan. Four of them partly feature companion diagnostics. When cancer gene panel test is used for the purpose of comprehensive gene profiling (CGP), a total of 56,000 points(44,000 points for the test administration fee and 12,000 points for the expert panel fee) can be claimed, whereas if the cancer gene panel test is used for the purpose of companion diagnostics, hospitals can claim only the reimbursement as a companion diagnostics, which fee is much cheaper than that of CGP. Therefore, cancer gene panel tests are rarely used as a companion diagnosis in daily clinical practice. Even when the test is performed as a CGP test, since its indication is limited to patients who have completed or are expected to complete standard chemotherapy, most biomarkers associated with approved drugs are already evaluated with stand-alone companion diagnostics at the time of CGP test application. On the other hand, there are some approved drugs, such as pembrolizumab for TMB-H or entrectinib or larotrectinib for NTRK fusion gene, for which there is no stand-alone companion diagnostics and the eligibility for these drugs cannot be judged without the results of CGP test. This paper discusses the current status and issues of companion diagnostics in cancer genomic medicine.

A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer.

Given the promising activity and tolerability of FOLFIRINOX as a second-line treatment for advanced biliary tract cancer (BTC), it can be an attractive first-line treatment option as well. This is a single-arm, open-label, multicenter phase II study to evaluate the safety and efficacy of FOLFIRINOX as a first-line treatment for patients with advanced BTC. Primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), tumor response and safety. This study defined primary endpoint might be met when the lower limit value of 80% confidence interval [CI] of the median PFS ≥ 6.0 months. Between June 2016 and March 2020, 35 BTC patients (21 intrahepatic, 10 extrahepatic, 2 gallbladder, 2 ampulla) including 26 unresectable and 9 recurrent disease were enrolled. After a median follow-up of 13.9 months, the median PFS and OS were 7.4 (80% CI, 5.5-7.5) and 14.7 (80% CI, 11.8-15.7) months, respectively. Complete response was achieved in 1 (2.9%) and partial response in 10 (28.6%), giving an objective response rate of 31.4% and disease control rate of 74.3%. Major grade 3-4 adverse events included neutropenia (54.3%), leukopenia (34.4%), febrile neutropenia (17.1%), thrombocytopenia (8.6%), cholangitis (8.6%), anemia, nausea, diarrhea, and peripheral sensory neuropathy (2.9% each). FOLFIRINOX was well tolerable in patients with advanced BTC, however, this study did not meet the primary endpoint to conduct a phase III trial. Thus, further explorations are required to find a subset of patients and/or certain clinical scenario which might be beneficial from FOLFIRINOX.

Impact of tumor shrinkage pattern with biweekly triplet gemcitabine+cisplatin+S-1 regimen for biliary tract cancers: Implications for neoadjuvant therapy from the data of KHBO1401 (KHBO1401-1A study).

BACKGROUND: The multicenter randomized phase III KHBO1401 study (gemcitabine+cisplatin+S-1 [GCS] versus GC in biliary tract cancers [BTC]) demonstrated that GCS not only prolonged patient survival but also achieved a high response rate and that it should be good for neoadjuvant therapy. Therefore, to explore the possibilities of neoadjuvant therapy, we investigated the tumor shrinkage pattern. METHODS: Among the total of 246 patients enrolled in the KHBO1401, the tumor shrinkage pattern and survival were investigated in patients with measurable BTC (n=183, 74%; GCS, n=91; GC, n=92). RESULTS: The tumor shrinkage pattern could be divided to 4 categories based on the response at 100 days after enrollment: category A (<-30% in size), B (-30% to 0%), C (0% to +20%), and D (>+20%). The GCS arm included more category A and B cases (61 [67%] vs. 33 [36%], P<0.0001). Each category predicted best response and overall survival (P<0.0001). Category A showed sustained tumor response compared with category B; in GCS, the time to maximum tumor response was 165 ± 76 days in category A and 139 ± 78 in category B. Categories C and D did not achieve tumor shrinkage. The maximum tumor shrinkage size in category A was -53% in the GCS arm and -65% in the GC arm (P=0.0892). Twenty percent of patients in the GCS showed tumor regrowth 154 ± 143 days later. CONCLUSION: GCS provided faster and greater tumor shrinkage with better survival in comparison to GC, although 20% of patients showed re-growth after 6 cycles.

Comprehensive review of undifferentiated carcinoma of the pancreas: from epidemiology to treatment.

Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer displaying no definitive direction of differentiation. UC has been reported as a highly aggressive malignant neoplasm, with a median overall survival of <1 year, except for several surgical series. On the other hand, UC tissue sometimes contains non-neoplastic osteoclast-like giant cells (OGCs), and such cases have been reported to have relatively longer survival. Thus, the World Health Organization (WHO) classification histologically distinguishes UC with OGCs (UCOGCs) from UC, and UCs were subclassified into three subtypes: anaplastic UC, sarcomatoid UC and carcinosarcoma. However, still less is known about UC due to its rarity, and such situations lead to further difficulties in treatment for UC. To date, only surgical resection can offer curative treatment for patients with UC, and no clear evidence for chemotherapy exists for them. However, a retrospective cohort study and case reports showed that relatively promising results paclitaxel-containing regimens for treatment of patients with unresectable UC. Furthermore, high programmed cell death protein 1 expression has been reported in sarcomatoid UCs and UCOGCs, and promising responses to anti-programmed death-ligand 1 therapy have been described in case reports of UCOGCs. Recent advances in chemotherapeutic agents and molecular technologies are opening up the possibilities for expanded treatments.

Association of Malnutrition With Physical Activity Intensity in Patients With Subacute Stroke.

OBJECTIVE: To investigate the relationship between nutritional status measured by the Global Leadership Initiative on Malnutrition (GLIM) criteria and the intensity of physical activity, and to determine the association between these factors and the activities of daily living (ADLs) in patients with subacute stroke during hospitalization. DESIGN: A cross-sectional study. SETTING: The study was conducted in the rehabilitation unit at a neurosurgical hospital. PARTICIPANTS: One hundred and twenty-eight patients with subacute stroke (N=128). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Nutritional status was assessed using GLIM criteria. Sedentary behavior (SB), light-intensity physical activity (LIPA), and moderate-to-vigorous physical activity (MVPA) were measured using an accelerometer. Multiple regression analysis was used to investigate the relationship between nutritional status and intensity of physical activity. Moreover, the association of nutritional status and physical activity intensity with ADLs was determined using multiple regression analysis and mediation analysis. RESULTS: Malnutrition was associated with SB time (B = 16.241, P=.009) and LIPA time (B = -17.656, P=.002), but not MVPA time (B = -0.472, P=.776). SB time (B = -0.063, P=.009) and LIPA time (B = 0.093, P<.001) were associated with functional independence measure for motor function, while MVPA time (B = -0.080, P=.379) was not. SB time (coefficient = -10.785, P<.001) and LIPA time (coefficient = -12.054, P<.001) were significant mediators between nutrition status and ADLs. CONCLUSIONS: Malnutrition was associated with a SB time and LIPA time, but not MVPA time, in patients with sub-acute stroke. SB and LIPA times were associated with ADLs and mediated between nutrition status and ADLs in these patients. The association of nutritional status on physical activity and ADLs should be considered in stroke rehabilitation.

Physical Activity as Measured by Accelerometers Predicts Functional Improvement in Older Patients Undergoing Hospital Rehabilitation.

This prospective cohort study aimed to investigate the association between physical activity (PA) as measured using accelerometers, and functional improvement measured using a short physical performance battery in older patients undergoing rehabilitation. After admission to the rehabilitation hospital, patients were categorized into quartile groups based on their level of PA measured using accelerometers. The primary outcome was physical function measured using the short physical performance battery at hospital discharge. A total of 204 patients were included in the analysis. After adjusting for confounding factors, light-intensity PA (p < .001) and moderate-to-vigorous-intensity PA (p < .001) were associated with a short physical performance battery at hospital discharge. In conclusion, PA at admission is positively associated with functional improvement in older patients undergoing hospital rehabilitation.

Relationship of Functional Outcome With Sarcopenia and Objectively Measured Physical Activity in Patients With Stroke Undergoing Rehabilitation.

This study aimed to investigate the relationship of Functional Independence Measure for motor function (FIM-M) with sarcopenia, and physical activity in patients with stroke undergoing rehabilitation. This cross-sectional study included patients with stroke at a single convalescent rehabilitation hospital. Sarcopenia was diagnosed based on the Asia Working Group for Sarcopenia 2019 criteria. Physical activity was measured as the duration of light-intensity physical activity and moderate to vigorous physical activity using a triaxial accelerometer. Of 80 patients (median age: 72.0 years), 46 (57.5%) were diagnosed with sarcopenia. In multivariate linear regression analysis, FIM-M score was significantly associated with sarcopenia (ß = -0.15, p = .043) and light-intensity physical activity (ß = 0.55, p < .001). In another model, FIM-M score was significantly associated with moderate to vigorous physical activity (ß = 0.27, p = .002) but not with sarcopenia. This study demonstrated that FIM-M was partially associated with sarcopenia and associated with physical activity regardless of intensity in patients with stroke.

Chronological improvement in precision oncology implementation in Japan.

In Japan, comprehensive genomic profiling (CGP) tests for refractory cancer patients have been approved since June 2019, under the requirement that all cases undergoing CGP tests are annotated by the molecular tumor board (MTB) at each government-designated hospital. To investigate improvement in precision oncology, we evaluated and compared the proportion of cases receiving matched treatments according to CGP results and those recommended to receive genetic counseling at all core hospitals between the first period (11 hospitals, June 2019 to January 2020) and second period (12 hospitals, February 2020 to January 2021). A total of 754 and 2294 cases underwent CGP tests at core hospitals in the first and second periods, respectively; 28 (3.7%) and 176 (7.7%) patients received matched treatments (p < 0.001). Additionally, 25 (3.3%) and 237 (10.3%) cases were recommended to receive genetic counseling in the first and second periods, respectively (p < 0.001). The proportion was associated with the type of CGP test: tumor-only (N = 2391) vs. tumor-normal paired (N = 657) analysis (10.0% vs. 3.5%). These results suggest that recommendations regarding available clinical trials in networked MTBs might contribute to increasing the numbers of matched treatments, and that tumor-normal paired rather than tumor-only tests can increase the efficiency of patient referrals for genetic counseling.

Expert panel consensus recommendations on the use of circulating tumor DNA assays for patients with advanced solid tumors.

Comprehensive genomic profiling is increasingly used to facilitate precision oncology based on molecular stratification. In addition to conventional tissue comprehensive genomic profiling, comprehensive genomic profiling of circulating tumor DNA has become widely utilized in cancer care owing on its advantages, including less invasiveness, rapid turnaround time, and capturing heterogeneity. However, circulating tumor DNA comprehensive genomic profiling has some limitations, mainly false negatives due to low levels of plasma circulating tumor deoxyribonucleic acid and false positives caused by clonal hematopoiesis. Nevertheless, no guidelines and recommendations fully address these issues. Here, an expert panel committee involving representatives from 12 Designated Core Hospitals for Cancer Genomic Medicine in Japan was organized to develop expert consensus recommendations for the use of circulating tumor deoxyribonucleic acid-based comprehensive genomic profiling. The aim was to generate guidelines for clinicians and allied healthcare professionals on the optimal use of the circulating tumor DNA assays in advanced solid tumors and to aid the design of future clinical trials that utilize and develop circulating tumor DNA assays to refine precision oncology. Fourteen clinical questions regarding circulating tumor deoxyribonucleic acid comprehensive genomic profiling including the timing of testing and considerations for interpreting results were established by searching and curating associated literatures, and corresponding recommendations were prepared based on the literature for each clinical question. Final consensus recommendations were developed by voting to determine the level of each recommendation by the Committee members.

Current status and issues related to secondary findings in the first public insurance covered tumor genomic profiling in Japan: multi-site questionnaire survey.

In June 2019, the Japanese National Health Insurance (NHI) system introduced coverage for two types of tumor genomic profiling (TGP): FoundationOneⓇ CDx (F1) and OncoGuide™ NCC OncoPanel System (NCCOP). TGP sometimes reveals germline variants that are potentially pathogenic as secondary findings (SFs). We conducted a questionnaire-based survey to find out the operational statuses of F1 and NCCOP at institutions where TGP was performed to elucidate issues related to SFs. Responses were received from 97 of 112 institutions (86.6%). As of May 31, 2020, 88 (90.7%) and 78 (80.4%) institutions started performing F1 and NCCOP, respectively. Since F1 only examines tumor samples, germline confirmatory testing is necessary to determine whether they are actually germline pathogenic variants (GPVs). When physicians are obtaining informed consent all but 2.3% of the patients requested SF disclosure. Conversely, when presumed germline pathogenic variants (PGPVs) were detected, 46.2% were not willing to receive confirmatory tests as they wanted to prioritize cancer treatment over SFs investigation, while only 23.3% underwent confirmatory tests. Problems in cancer genomic medicine reported by clinical genetics departments included short-staffing (n = 10), insufficient interdepartmental cooperation (n = 9), inconsistent understanding of genetics among healthcare professionals (n = 8), and low utilization rate of SFs due to lack of insurance coverage for confirmatory tests and post-test health checkups (n = 8). Solutions include; determining the appropriate timing to confirm patient intent on SF disclosure, covering confirmatory tests for PGPVs by the NHI, and establishing cooperation between the oncology and clinical genetics departments.

Determinants of Peak Oxygen Uptake at Each Stage of Renal Dysfunction in Patients with Heart Disease.

Background: Identifying the causes of low peak oxygen uptake (peak V̇ O 2 ) in heart disease patients with renal dysfunction is necessary for prognostic improvement strategies. The purpose of this study was to verify the determinants of peak V̇ O 2 for each stage of renal function in heart disease patients, focusing on end-tidal oxygen partial pressure ( PETO 2 ). Methods: Two hundred fifty heart disease patients who underwent cardiopulmonary exercise testing (CPET) in our institution were consecutively enrolled. Patients were divided into three groups by their estimated glomerular filtration rate (eGFR): < 45, 45-59 and ≥ 60 mL/min/1.73 m 2 . Patient characteristics and CPET parameters including Δ 2 (rest-anaerobic threshold) were compared between the groups. The relationship between Δ PETO PETO 2 and peak V̇ O 2 was also investigated for each group. Results: In total, 201 patients were analyzed. Δ PETO 2 decreased with the deterioration of renal function (eGFR < 45, 0.1 mmHg vs. eGFR 45-59, 2.4 mmHg vs. eGFR ≥ 60, 5.2 mmHg, p < 0.001). In the eGFR < 45 group, left ventricular ejection fraction (LVEF) and hemoglobin (Hb) were significantly associated with peak V̇ O 2 ß = 0.518, p < 0.001 and ß = 0.567, p < 0.001, respectively), whereas Δ PETO 2 was not. In the eGFR 45-59 group, age, Hb, and Δ PETO 2 showed a significant association with peak V̇ O 2 ( ß = -0.354, p = 0.006; ß = 0.258, p = 0.007; ß = 0.501, p < 0.001; respectively). In the univariate analysis, eGFR 45-59 group showed the highest coefficient of determination of Δ PETO 2 to peak V̇ O 2 ( R 2 = 0.247, p < 0.001). Conclusions: The determinants of peak V̇ O 2 in heart disease patients depended on the stage of renal function. The determinants of peak V̇ O 2 in patients with eGFR < 45 were LVEF and Hb, while Δ PETO 2 was the strongest predictor of peak V̇ O 2 in patients with eGFR 45-59.

Impact of neoadjuvant intensity-modulated radiation therapy on borderline resectable pancreatic cancer with arterial abutment; a prospective, open-label, phase II study in a single institution.

BACKGROUND: Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A). METHODS: A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT. RESULTS: Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19-9 (CA19-9) > 400 U/ml before NACIMRT. CONCLUSIONS: NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment. TRIAL REGISTRATION: UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011776 Registration number: UMIN000010113. Date of first registration: 01/03/2013.

Relationship between physical function at discharge and hospital meal intake in elderly patients with heart failure.

The relationship between low physical function (LPF) at discharge and food intake percentage (FIP) during hospitalization is unclear. We aimed to clarify the relationship between LPF at discharge and FIP and the change in nutritional status during hospitalization in elderly patients with heart failure (HF), and determine cutoff values for FIP and change in nutritional status during hospitalization. We included 431 consecutive patients aged ≥ 65 years who were hospitalized for HF and underwent cardiac rehabilitation (CR) from 2017 to 2019. Physical function at discharge was classified into two groups according to the Short Performance Physical Battery (SPPB): low physical function (LPF) (SPPB ≤ 9) and high physical function (HPF) (SPPB > 9). We compared background, clinical parameters, pre-hospital walking level, CR progress, nutritional factors during hospitalization including FIP of the main dish and side dish, and changes in nutritional status using the Geriatric Nutritional Risk Index (ΔGNRI) at admission and discharge. Multiple logistic regression analysis was also performed. The final analysis included 213 patients (age, 81.6 years) divided into the LPF (n = 136) and HPF groups (n = 77). The LPF group showed low FIP and a high ΔGNRI value. Multivariate analysis showed FIP main dish, ΔGNRI, worsening renal function, pre-hospital walking level, and days to start of walking to be factors influencing LPF at discharge. Respective cutoff values for FIP main dish and ΔGNRI predicting LPF at discharge were 82.2% and 4.24. FIP main dish during hospitalization and ΔGNRI were associated with LPF at discharge.

Older phase 2 cardiac rehabilitation patients engaged in gardening maintained physical function during the COVID-19 pandemic.

This study aimed to clarify the effects of gardening on hemodynamic response, rating of perceived exertion (RPE) during exercise, and body weight in patients in whom phase 2 cardiac rehabilitation (CR) was interrupted due to the Coronavirus disease 2019 (COVID-19) pandemic. Among 76 outpatients participating in consecutive phase 2 CR in both periods from March to April and June to July 2020, which were before and after CR interruption, respectively, at Sanda City Hospital were enrolled. The inclusion criterion was outpatients whose CR was interrupted due to COVID-19. Patients under the age of 65 were excluded. We compared the data of hemodynamic response and RPE during exercise on the last day before interruption and the first day after interruption when aerobic exercise was performed at the same exercise intensity in the gardener group and the non-gardener group. Forty-one patients were enrolled in the final analysis. After CR interruption, the gardener group did not show any significant difference in all items, whereas the non-gardener group experienced significant increase in HR (Peak) (p = 0.004) and worsening of the Borg scale scores for both dyspnea and lower extremity fatigue (p = 0.039 and p = 0.009, respectively). Older phase 2 CR patients engaged in gardening did not show any deterioration in hemodynamic response or RPE during exercise, despite CR interruption and refraining from going outside. Gardening may be recommended as one of the activities that can maintain or improve physical function in older phase 2 CR patients during the COVID-19 pandemic.

Germline sequencing for presumed germline pathogenic variants via tumor-only comprehensive genomic profiling.

BACKGROUND: The European Society for Medical Oncology Precision Medicine Working Group (ESMO-PMWG) published recommendations regarding confirmatory germline testing for presumed germline pathogenic variants (PGPVs) in tumor-only comprehensive genomic profiling (CGP). However, the clinical validity of these recommendations has not been investigated in a real-world practice. METHODS: Medical records of 180 consecutive patients who obtained the results of a tumor-only CGP (FoundationOne® CDx, Foundation Medicine, Inc, Cambridge, MA, USA) between October 2018 and March 2020, were retrospectively reviewed. After excluding patients with no reported variants in 45 actionable genes (n = 6), or no archived germline DNA samples (n = 31), 143 patients were investigated. The PGPVs were selected from the CGP report and germline sequencing were performed using DNA samples archived in Clinical Bioresource Center in Kyoto University Hospital (Kyoto, Japan). RESULTS: A total of 195 variants were classified as PGPV based on the conventional criteria. Germline sequencing disclosed that 12 variants (6.2%) were of germline origin. In contrast, after filtering these 195 variants through the ESMO-PMWG recommendation criteria for confirmatory germline testing, following seven PGPVs, BRCA2 (n = 2), BRIP1 (n = 1), BAP1 (n = 1), PMS2 (n = 1), MSH2 (n = 1), and SDHB (n = 1) remained and six variants (85.7%) were confirmed to be of germline origin. CONCLUSION: Our current data suggested that the application of ESMO-PMWG criteria is helpful in selecting PGPVs with a high likelihood of germline origin in a tumor-only CGP in daily clinical practice.