Evaluation of potential complication of interstitial lung disease with abemaciclib and palbociclib treatments

Background: Various cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have demonstrated promising anti-tumor effects. The Japanese Ministry of Health, Labour and Welfare has issued a warning about interstitial lung diseases as an adverse effect of CDK4/6 inhibitors. However, a large-scale evaluation of potential complications has not been conducted to date, and the occurrence of these adverse effects is unclear. Aim: The aim of this study was to evaluate the clinical incidence of interstitial lung disease caused by two CDK4/6 inhibitors, abemaciclib and palbociclib, and assess the relationship between each drug and interstitial lung disease. Methods and results: We evaluated the relationship between the CDK4/6 inhibitors (abemaciclib and palbociclib) and interstitial lung disease in clinical practice using data from the Japanese Adverse Drug Event Report (JADER) database and FDA Adverse Event Reporting System (FAERS) to detect adverse event signals with reported odds ratios (RORs). Furthermore, we performed an adverse event-time analysis for each drug using data from the JADER database to examine the time of onset of the adverse events. The analysis of the reports in the JADER database showed that the lower limit of the 95% confidence interval (CI) of ROR for abemaciclib was >1 regardless of age, and a signal was detected. Interstitial lung disease associated with abemaciclib and palbociclib use has been reported, with an average onset period from treatment initiation [median (25th-75th quartile)] of 65.1 [56.0 days (25.3-98.3 days)] and 53.1 days [38.0 days (10.8-76.0 days)], respectively. The analysis of the reports in the FAERS showed that the lower limit of the 95% CI of the ROR for the two drugs was >1, and a signal was detected. Conclusion: Treatment with abemaciclib and palbociclib is associated with a potential complication of interstitial lung disease, regardless of age

ILD CAUSED BY ANTIFIBROTIC AGENTS

Interstitial lung disease (ILD), as an adverse effect of certain drugs, leads to inflammation and damage in the walls of the alveoli, making it difficult for the alveoli to take up oxygen. Interstitial pneumonia with no identifiable cause is called idiopathic interstitial pneumonia (IIP), and, among the major IIPs, idiopathic pulmonary fibrosis (IPF) is diagnosed in about half of patients. Current treatment options are limited, among which the antifibrotic drugs nintedanib (Ofev) and pirfenidone (Pirespa) are the first-line drugs. In this study, we investigated the incidence of ILD possibly caused by antifibrotic agents using data from the Japanese Adverse Drug Event Report (JADER) database, a database of spontaneous adverse event reports published by the Pharmaceuticals and Medical Devices Agency (PMDA), and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), published by the FDA. We used the FAERS and JADER to detect the signals of adverse events on the basis of reporting odds ratios. The relationship between indications and adverse events was clarified by separating indications and adverse events using the spontaneous adverse event reporting database with novel drug involvement. Regarding the involvement of nintedanib and pirfenidone in the development of ILD, JADER and FAERS showed signals for both nintedanib and pirfenidone as suspect drugs, and no signals for nintedanib or pirfenidone as concomitant drug interactions were detected. We highlight this because there are only a few effective drugs for IPF, and effective and safe drug therapies should be implemented by taking into consideration drug-induced ILD

Drug-Repositioning Approaches Based on Database

Drug repositioning is a drug discovery strategy in which an existing drug is utilized as a therapeutic agent for a different disease. As information regarding the safety, pharmacokinetics, and formulation of existing drugs is already available, the cost and time required for drug development is reduced. Conventional drug repositioning has been dominated by a method involving the search for candidate drugs that act on the target molecules of an organism in a diseased state through basic research. However, recently, information hosted on medical information and life science databases have been used in translational research to bridge the gap between basic research in drug repositioning and clinical application. Here, we review an example of drug repositioning wherein candidate drugs were found and their mechanisms of action against a novel therapeutic target were identified via a basic research method that combines the findings retrieved from various medical and life science databases

Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer : a single-institution retrospective study

Immune checkpoint inhibitors (ICIs) elicit antitumour effects by activating the host immunity and cause immune-related adverse events (irAEs). ICI-related interstitial lung disease (ICI-ILD) is a fatal irAE that is difficult to treat; moreover, its incidence is relatively higher in patients with lung cancer. Therefore, early ICI-ILD detection and intervention are important for patient safety. However, a risk assessment method for ICI-ILD has not been established and the prediction of ICI-ILD occurrence is difficult. The aim of our study was to identify the risk factors associated with ICI-ILD. To this end, we retrospectively analysed 102 patients with lung cancer who first received ICI and completed the treatment between April 2016 and December 2019 at Tokushima University Hospital. Nineteen patients had all grades of ICI-ILD and 10 had grade ≥ 3 ICI-ILD. The 30-day mortality rate of patients with grade ≥ 3 ICI-ILD was the highest among all patients (P < 0.01). The multivariate logistic analysis indicated that the performance status ≥ 2 alone and both performance status ≥ 2 and ≥ 50 pack-year were independent risk factors of ICI-ILD of grade ≥ 3 and all grades, respectively. Overall, our study provides insights to predict ICI-ILD occurrence

Impact of lymph node dissection on clinical outcomes of intrahepatic cholangiocarcinoma: Inverse probability of treatment weighting with survival analysis

Background: Lymph node metastasis (LNM) has been established as a critical risk factor for prognosis in intrahepatic cholangiocarcinoma (ICC). The clinical implications of lymph node dissection (LND) have been debated. This study aimed to clarify the prognostic impact of LND by multicenter retrospective analysis. Methods: A total of 310 ICC patients who had undergone curative resection between 2000 and 2016 were retrospectively analyzed. The prognostic impact of LND was estimated under an inverse probability of treatment weighting (IPTW) approach using propensity scores. Results: LND was performed for 224 patients (72%), with LNM pathologically confirmed in 90 patients (40%). Prognosis was poorer for patients with LNM (median survival, 16.9 months) than for those without (57.2 months; P Conclusions: LND could have a significant role to play in improving oncologic outcomes. Therapeutic LND should be implemented on the basis of tumor location and tumor advancement

スイビブガン ノ ゾウ オ シメシタ スイナイ フクヒ ノ 1レイ

Intrapancreatic accessory spleens exhibit the same computed tomography （CT） findings as the spleen itself. We experienced a case in which an intrapancreatic accessory spleen mimicked pancreatic tail carcinoma. A ５４-year-old female who had a medical history of splenectomy presented with a pancreatic tail tumor, which exhibited low density in the arterial phase and slightly high density in the portal and equilibrium phases on CT. In addition, an accessory spleen was present in the greater omentum. We initially diagnosed the tumor as a pancreatic carcinoma, and scheduled distal pancreatectomy（DP）combined with lymph node dissection（LND）. Intraoperatively, the tumor was found to be elastic-soft, which indicated that it might be benign. We changed the planned procedure from DP combined with LND to DP without LND. The cut surface of the tumor had the appearance of spleen tissue, and the pathological diagnosis was an intrapancreatic accessory spleen. Intrapancreatic accessory spleens can display the same imaging findings as pancreatic carcinomas. Intraoperative palpation and gross pathological examinations were useful for selecting the optimal surgical procedure in the present case. It is important to differentiate pancreatic tail tumors that exhibit low density in the arterial phase on CT from accessory spleens

Atomic-scale flattening of SiC surfaces by electroless chemical etching in HF solution with Pt catalyst

The authors present a method for flattening SiC surfaces with Pt as a catalyst in HF solution. The mechanism for flattening SiC surfaces is discussed. The flattened 4H-SiC (0001) surface is composed of alternating wide and narrow terraces with single-bilayer-height steps, which are induced by the rate difference of the catalytic reactions between adjacent terraces. Scanning tunneling microscopy images reveal a 1×1 phase on the terraces. The 1×1 phase is composed of coexisting of F- and OH-terminated Si atoms, which originate from the polarization of the underlying Si-C bonds. © 2007 American Institute of Physics.Kenta Arima, Hideyuki Hara, et al. "Atomic-scale flattening of SiC surfaces by electroless chemical etching in HF solution with Pt catalyst", Appl. Phys. Lett. 90(20), 202106 (2007) https://doi.org/10.1063/1.2739084

フククウキョウカ イ ゼンテキジュツゴ ニ 2ド ノ Petersen’s hernia シュウフクジュツ オ ヨウシタ 1レイ

Petersen’s hernia is a type of internal hernia that may occur after Roux-en-Y reconstruction. Some surgeons suture Petersen’s defect for prevention of Petersen’s hernia. We report a case of recurrent Petersen’s hernia. A fifty-something man underwent laparoscopic-assisted total gastrectomy with antecolic Roux-en-Y reconstruction for gastric cancer. Petersen’s hernia occurred ６ months later. We closed Petersen’s defect by absorbable suture. However, he experienced recurrence２months later. The defect had not been successfully closed and there was no adhesion ; thus, we sutured Petersen’s defect again, more tightly than before. Additionally, we investigated different approaches for closing Petersen’s defect due to our experience of recurrent Petersen’s hernia

Surgical Outcome of Patients Undergoing Pancreaticoduodenectomy: Analysis of a 17-Year Experience at a Single Center

The operative mortality and morbidity of pancreaticoduodenectomy (PD) remain high. We analyzed PD patientsʼ clinical characteristics and surgical outcomes and discuss how PD clinical outcomes could be improved. We retrospectively reviewed the cases of 400 patients who underwent a PD between January 1998 and April 2014 at Okayama University Hospital, a very-high-volume center. We identified and compared the clinical outcomes between two time periods (period 1: 1998-2006 vs. period 2: 2007-2014). The total postoperative mortality and major complication rates were 0.75 and 15.8 , respectively, and the median postoperative length of stay (LOS) was 32 days. Subsequently, patients who underwent a PD during period 2 had a significantly shorter LOS than those who underwent a PD during period 1 (29 days vs. 38.5 days, p＜0.001). The incidence of mortality and major complications did not differ between the two periods. In our multivariate analysis, period 1 was an independent factor associated with a long LOS (p＜0.001). The improvement of the surgical procedure and perioperative care might be related to the shorter LOS in period 2 and ot the consistently maintained low mortality rate after PD. The development of multimodal strategies to accelerate postoperative recovery may further improve PDʼs clinical outcomes