A consensus statement from the Japan Diabetes Society (JDS): a proposed algorithm for pharmacotherapy in people with type 2 diabetes-2nd Edition (English version).

The Japan Diabetes Society (JDS) adopted a sweeping decision to release consensus statements on relevant issues in diabetes management that require updating from time to time and launched a "JDS Committee on Consensus Statement Development." In March 2020, the committee's first consensus statement on "Medical Nutrition Therapy and Dietary Counseling for People with Diabetes" was published. In September 2022, a second consensus "algorithm for pharmacotherapy in people with type 2 diabetes" was proposed. In developing an algorithm for diabetes pharmacotherapy in people with type 2 diabetes, the working concept was that priority should be given to selecting such medications as would appropriately address the diabetes pathology in each patient while simultaneously weighing the available evidence for these medications and the prescribing patterns in clinical practice in Japan. These consensus statements are intended to present the committee's take on diabetes management in Japan, based on the evidence currently available for each of the issues addressed. It is thus hoped that practicing diabetologists will not fail to consult these statements to provide the best available practice in their respective clinical settings. Given that the persistent dual GIP/GLP-1 receptor agonist tirzepatide was approved in April 2023, these consensus statements have been revised1). In this revision, specifically, tirzepatide was added to the end of [likely involving insulin resistance] of "Obese patients" in Step 1: "Select medications to address the diabetes pathology involved" in Fig. 2. While the sentence, "Insulin insufficiency and resistance can be assessed by referring to the various indices listed in the JDS 'Guide to Diabetes Management.' was mentioned in the previous edition as well, "While insulin resistance is analogized based on BMI, abdominal obesity, and visceral fat accumulation, an assessment of indicators (e.g., HOMA-IR) is desirable" was added as information in order to more accurately recognize the pathology. Regarding Step 2: "Give due consideration to safety," "For renal excretion" was added to the "Rule of thumb 2: Avoid glinides in patients with renal impairment." The order of the medications in "rule of thumb 3: Avoid thiazolidinediones and biguanides in patients with heart failure (in whom they are contraindicated)." to thiazolidinediones then biguanides. In the description of the lowest part of Fig. 2, for each patient failing to achieve his/her HbA1c control goal, "while reverting to step 1" was changed to "while reverting to the opening" and "including reassessment if the patient is indicated for insulin therapy" was added. In the separate table, the column for tirzepatides was added, while the two items, "Characteristic side effects" and "Persistence of effect" were added to the area of interest. The revision also carried additional descriptions of the figure and table such as tirzepatides and "Characteristic side effects" in the statement, and while not mentioned in the proposed algorithm figure, nonalcoholic fatty liver disease (NAFLD) is covered from this revision for patients with comorbidities calling for medical attention. Moreover, detailed information was added to the relative/absolute indication for insulin therapy, the Kumamoto Declaration 2013 for glycemic targets, and glycemic targets for older people with diabetes. Again, in this revision, it is hoped that the algorithm presented here will not only contribute to improved diabetes management in Japan, but will continue to evolve into a better algorithm over time, reflecting new evidence as it becomes available.

Improvement of Mucoid Impaction with Dupilumab in a Severe Asthma Patient.

Different from intrabronchial mucus accumulation in bronchiectasis caused by chronic inflammation, mucoid impactions are observed in patients with allergic bronchopulmonary aspergillosis (ABPA) and bronchial asthma. A 62-year-old man was referred to our hospital for treatment of bronchial asthma. Five years ago, he had a coronary stent insertion for myocardial infarction and was diagnosed with bronchial asthma. The stent was suspected to be related to the onset of asthma. Inhaled corticosteroid/long-acting beta agonist was not sufficient to control the condition. He received dupilumab, a humanized anti-human IL-4/13 receptor monoclonal antibody (biologic therapy). Bronchial mucoid impactions disappeared by single administration of the biologic therapy and there has been no recurrence of mucoid impactions for over a year. Although very rare, we do believe that information regarding asthma phenotype in this patient, indication and administration method for dupilumab, and changes before and after administration of dupilumab will provide some suggestive information on treatment for patients with a similar course in the future.

Development of Pseudochylothorax in a Patient with Lung Squamous Cell Carcinoma and Rheumatoid Arthritis.

Pseudochylothorax is a rare disease entity. It is characterized by a milky white pleural fluid with a cholesterol/triglyceride ratio >1. According to published reports, most patients had associated diseases, including rheumatoid arthritis and tuberculosis, with only one patient having oropharynx carcinoma associated with lung metastases. Herein, we describe the development of pseudochylothorax in a patient with rheumatoid arthritis and lung squamous cell carcinoma. Cancer cells were confirmed in the pleural fluid, but there was no thoracic duct damage caused by cancer invasion or tuberculosis-related lesions in the lung field or intrathoracic lymph nodes. Anticancer treatment included immune checkpoint inhibitors, and the appearance of a cavity within the mass and pneumothorax were associated with lung cancer treatment. Although the mechanism of pseudochylothorax onset was unknown, we do believe that this clinical course would provide some suggestive information on treatment for patients with a similar course in the future.

A consensus statement from the Japan Diabetes Society: A proposed algorithm for pharmacotherapy in people with type 2 diabetes - 2nd edition (English version).

This algorithm was issued for the appropriate use of drugs for the treatment of type 2 diabetes mellitus in Japan. The revisions include safety considerations, fatty liver disease as a comorbidity to be taken into account and the position of tirzepatide.

Investigation of age and smoking in NSCLC patients with uncommon EGFR mutations.

Introduction: In addition to the two common epidermal growth factor receptor (EGFR) mutations, there are many uncommon mutations. Due to the high number of uncommon types, as well as the rarity of patients, there is lack of information regarding patient demographics, especially age distribution and smoking status. Against this background, we conducted an analysis to clarify the background of patients with uncommon EGFR mutations, especially considering their age distribution and smoking status. Materials and Methods: We retrospectively reviewed the medical records of non-small cell lung cancer (NSCLC) patients diagnosed in a multicenter clinical practice from 2002 to 2023. Patients included all cases of non-advanced and advanced NSCLC with uncommon EGFR mutations. Result: Information on 158 patients with uncommon EGFR mutation was collected. Median age was 72 years, with the age distribution showing that most patients were in their 70s. There was a significant difference between the proportion of patients aged up to 59 years and the proportion aged 75 years or older. In 88 patients with a smoking habit history, a significant correlation was found between smoking index and age. Among non-smokers, there was a peak between ages 70 and 74, which was older than the peak among smokers. Conclusions: Even in elderly patients and NSCLC patients with a history of smoking, although it is unclear whether EGFR mutation is common or uncommon, EGFR gene testing should be performed considering the possibility of these patients being EGFR-positive.

Real Clinical Practice of Combined Atezolizumab Plus Chemotherapy in Patients With Small Cell Lung Cancer.

BACKGROUND/AIM: Atezolizumab, an anti-PD-L1 antibody, has been increasingly administered in combination with chemotherapy to patients with small cell lung cancer (SCLC). This study aimed to determine how patients with extensive disease (ED) -SCLC responded to atezolizumab with chemotherapy and found factors affecting long-term response and survival. PATIENTS AND METHODS: This study focused on patients with SCLC who were treated with a combination of atezolizumab and chemotherapy in Japan between 2019 and 2023. Patient information and tumor response were analyzed, along with adverse events. We compared data and estimated survival probabilities. RESULTS: In our clinical trial, 95 patients with SCLC who received this treatment had a median progression-free survival of 6.0 months and a median overall survival of 15.0 months. Immune-related adverse events were observed in 13.7% of the patients, with grade 3 or higher in 5.3%. The efficacy and immune-related adverse events associated with this treatment regimen were comparable to those reported in previous clinical trials. Progression-free survival >2 years was observed in a small number of patients (5.3%). CONCLUSION: Our research will offer important insights for the future care of patients with extensive-stage SCLC by utilizing atezolizumab in combination with chemotherapy. Accumulation and confirmation of clinical practice results will have important implications for the future implementation of this therapy.

Edge-Terminated AlGaN/GaN/AlGaN Multi-Quantum Well Impact Avalanche Transit Time Sources for Terahertz Wave Generation.

In our pursuit of high-power terahertz (THz) wave generation, we propose innovative edge-terminated single-drift region (SDR) multi-quantum well (MQW) impact avalanche transit time (IMPATT) structures based on the AlxGa1-xN/GaN/AlxGa1-xN material system, with a fixed aluminum mole fraction of x = 0.3. Two distinct MQW diode configurations, namely p+-n junction-based and Schottky barrier diode structures, were investigated for their THz potential. To enhance reverse breakdown characteristics, we propose employing mesa etching and nitrogen ion implantation for edge termination, mitigating issues related to premature and soft breakdown. The THz performance is comprehensively evaluated through steady-state and high-frequency characterizations using a self-consistent quantum drift-diffusion (SCQDD) model. Our proposed Al0.3Ga0.7N/GaN/Al0.3Ga0.7N MQW diodes, as well as GaN-based single-drift region (SDR) and 3C-SiC/Si/3C-SiC MQW-based double-drift region (DDR) IMPATT diodes, are simulated. The Schottky barrier in the proposed diodes significantly reduces device series resistance, enhancing peak continuous wave power output to approximately 300 mW and DC to THz conversion efficiency to nearly 13% at 1.0 THz. Noise performance analysis reveals that MQW structures within the avalanche zone mitigate noise and improve overall performance. Benchmarking against state-of-the-art THz sources establishes the superiority of our proposed THz sources, highlighting their potential for advancing THz technology and its applications.

Control of pleural effusion with prednisolone in a patient with yellow nail syndrome: A case report.

Yellow nail syndrome (YNS) can induce bilateral exudative pleural effusion; however, to the best of our knowledge, no standard treatment for YNS has been established. The present study describes a patient with YNS for whom the pleural effusion was controlled by prednisolone. A 73-year-old man was referred to the University of Tsukuba Hospital (Ibaraki, Japan) complaining of shortness of breath, which was diagnosed as being due to bilateral pleural effusion. Based on the presence of yellowing and growth retardation of the toenails, lymphedema, bilateral exudative pleural fluid of unknown etiology, and lymphatic congestion on lymphoscintigraphy, the patient was diagnosed with YNS. The pleural fluid was predominantly lymphocytic and responded to systemic steroid administration [prednisolone 30 mg/day (0.5 mg/kg) for 2 weeks, with subsequent weekly tapering]. The general condition of the patient and their dyspnea also improved with treatment. These findings indicated that systemic steroid administration should be considered as one of the treatment options for patients with YNS who are reluctant to undergo chest drainage or pleurodesis due to the potential for a decrease in their ability to perform daily activities and respiratory function.

Patient Age and EGFR-positive Non-small Cell Lung Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIM: The median age of subjects in many clinical trials of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor conducted to date has been approximately 60 years. However, it is not uncommon to encounter EGFR gene-positive patients in their 70s or 80s. Based on information obtained from these clinical trials, EGFR gene-positive non-small cell lung cancer (NSCLC) patients are considered to be younger than EGFR-negative patients. In this study, we analyzed clinical data to identify whether this assumption is true. PATIENTS AND METHODS: We retrospectively reviewed the medical records of NSCLC patients diagnosed in a multicenter clinical practice from 2009 to 2023. Patients included all cases of non-advanced and advanced NSCLC. RESULTS: Information on 2,540 patients, including 605 EGFR gene-positive patients, was collected. The median age of EGFR-positive and EGFR-negative patients was 72 years and 71 years, respectively, and there was no significant difference in the age of patients between these two groups (p=0.7887). The most common age in these two groups was 70 years. Among the EGFR gene subtypes, the frequency of exon 19 deletion decreased with age, whereas that of EGFR L858R increased. CONCLUSION: Patients in their 70s and 80s with non-small cell lung cancer were relatively frequently EGFR gene-positive. To avoid missing out on treatment opportunities, EGFR gene testing should also be performed on patients in this age group.

Hypersensitivity Pneumonitis Due to Living Environmental Pollution Caused by Masked Musangs.

Hypersensitivity pneumonitis is an allergic disease caused by various factors such as animal proteins and chemicals. The masked musang, a small animal of the Viverridae family native to East Asia, tends to infiltrate spaces like the attics of residences, causing damage through the deposition of excrement and other means. The older Japanese patient had been experiencing cough, shortness of breath, and fever for two months before presenting to our hospital. The symptoms improved upon admission to a local medical facility but deteriorated upon discharge. This cycle was repeated twice before the patient was admitted to our hospital. Based on the recurrent pattern of improvement during hospitalization and exacerbation upon returning home, along with the results of CT imaging and bronchoscopy, we suspected hypersensitivity pneumonitis. An environmental investigation at the patient's residence revealed a masked musang nest in the attic above the patient's room. After cleaning the attic, the symptoms did not recur. Consequently, we diagnosed hypersensitivity pneumonitis due to living environmental pollution caused by masked musangs. To the best of our knowledge, there have been no previous case reports of hypersensitivity pneumonitis caused by masked musangs. When wild animals invade human living environments, there is a possibility that not only infectious diseases but also immunological disorders, including allergic diseases, may appear.

Quantitative analysis of change in bone volume 5 years after sinus floor elevation using plate-shaped bone substitutes: a prospective observational study.

PURPOSE: Tricalcium phosphate (TCP) has osteoconductive ability and reportedly offers similar clinical results as autogenous bone grafts in dental implant treatment. However, few reports quantify temporal changes in augmented bone volume after sinus augmentation. We aimed to establish a three-dimensional (3D) quantification method to assess bone volume after sinus augmentation and to evaluate biocompatibility of the TCP plate. METHODS: Maxillary sinus floor augmentation was performed employing the lateral window technique, and plate-shaped ß-TCP (TCP plate) was used instead of granular bone grafting materials. After lifting the sinus membrane, the TCP plate was inserted and supported by dental implants or micro-screws. The changes in bone volumes in the maxillary sinus before and after surgery were recorded using cone-beam computed tomography, saved as Digital Imaging and Communications in Medicine-formatted files, and transformed to Standard Triangle Language (STL)-formatted files. Pre- and post-operative STL data of bone volume were superimposed, and the augmented bone volume was calculated. Moreover, changes in bone volumes, TCP plate resorption rates, and bone heights surrounding the implants were three dimensionally quantified. RESULTS: Fifteen implants in nine subjects were included in this study. TCP plates secured long-term space making, with results similar to those of granular bone substitutes. Newly formed bone was identified around the implant without bone graft material. TCP plate was absorbed and gradually disappeared. CONCLUSIONS: A novel 3D quantification method was established to evaluate changes in bone volume. Clinical application of TCP plate in sinus augmentation could be a better procedure in terms of prognosis and safety.

Prognostic Impact of Preoperative Assessment of Muscle Mass and Strength in Surgically Resected Lung Cancer.

BACKGROUND/AIM: The association between resected non-small cell lung cancer (NSCLC) and long-term outcomes of muscle mass depletion and muscle weakness has also not been well documented. This study evaluated whether muscle mass depletion assessed by bioelectrical impedance analysis (BIA) and low muscle strength assessed by the peak expiratory flow rate as a percentage of predicted value (%PEFR) were associated with surgical outcomes in patients with resected NSCLC. PATIENTS AND METHODS: This retrospective study included 219 patients with resected NSCLC between 2016 and 2021. The cutoff value for muscle mass depletion was according to guidelines, for low muscle strength, we defined by receiver operating characteristics analysis for recurrence-free survival (RFS). Survival analysis was performed, and postoperative outcomes were compared. RESULTS: A total of 76 patients (34.7%) had muscle mass depletion, and 114 patients (52.1%) had low muscle strength. Muscle mass depletion and low muscle strength were independent poor prognostic factors for overall survival [hazard ratio (HR)=2.631, p=0.003; HR=1.983, p=0.044] and RFS (HR=3.120, p<0.001; HR=1.857, p=0.028) in multivariate analysis. Postoperative complication was associated with low muscle strength (p=0.009). Postoperative recurrence was associated with muscle mass depletion (p=0.03). CONCLUSION: Preoperative muscle mass depletion assessed by BIA and low muscle strength determined by %PEFR are worse prognostic factors after surgical resection for NSCLC. Our results may provide some important information for preoperative management.

Long­term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli: A case report.

Systemic emboli are not uncommon in patients with advanced non-small cell lung cancer. The present study describes a rare case of long-term control in a patient with lung adenocarcinoma, nonbacterial thrombotic endocarditis and multiple systemic emboli. Briefly, a 56-year-old man was diagnosed with metastatic lung adenocarcinoma and was treated with pembrolizumab, which was discontinued due to the appearance of a pulmonary immune-related adverse event. During the clinical course, the patient developed pseudo-progression of a brain tumor, repeated thromboembolism in multiple organs and a small vegetation attached to the aortic valve. These lesions were controlled with apixaban after heparin therapy for >3 years. Lung cancer was subsequently treated with pemetrexed and bevacizumab; however, this treatment was terminated due to a complete response and the patient's request to discontinue treatment. More than 3 years have passed since the diagnosis of lung adenocarcinoma, and the patient has been followed up at the hospital without signs of cancer recurrence. Although unusual, the patient's course may provide useful suggestions for the treatment of other patients with a similar evolution.

On-Chip Modification of Titanium Electrothermal Characteristics by Joule Heating: Application to Terahertz Microbolometer.

This study demonstrates the conversion of metallic titanium (Ti) to titanium oxide just by conducting electrical current through Ti thin film in vacuum and increasing the temperature by Joule heating. This led to the improvement of electrical and thermal properties of a microbolometer. A microbolometer with an integrated Ti thermistor and heater width of 2.7 µm and a length of 50 µm was fabricated for the current study. Constant-voltage stresses were applied to the thermistor wire to observe the effect of the Joule heating on its properties. Thermistor resistance ~14 times the initial resistance was observed owing to the heating. A negative large temperature coefficient of resistance (TCR) of -0.32%/K was also observed owing to the treatment, leading to an improved responsivity of ~4.5 times from devices with untreated Ti thermistors. However, this does not improve the noise equivalent power (NEP), due to the increased flicker noise. Microstructural analyses with transmission electron microscopy (TEM), transmission electron diffraction (TED) and energy dispersive X-ray (EDX) confirm the formation of a titanium oxide (TiOx) semiconducting phase on the Ti phase (~85% purity) deposited initially, further to the heating. Formation of TiOx during annealing could minimize the narrow width effect, which we reported previously in thin metal wires, leading to enhancement of responsivity.

Extended ICI treatment after first-line chemoimmunotherapy could predict the clinical benefit of ramucirumab plus docetaxel in advanced non-small lung cancer: Post hoc analysis from NEJ051 (REACTIVE study).

BACKGROUND: The factors that predict the clinical response to ramucirumab plus docetaxel (RD) after first-line chemoimmunotherapy are unresolved. We explored whether the therapeutic efficacy of prior chemoimmunotherapy could predict the outcome of RD as sequential therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Our study comprised 288 patients with advanced NSCLC who received RD as the second-line treatment after first-line chemoimmunotherapy at 62 Japanese institutions. Chemoimmunotherapy consisted of a platinum-based regimen and immune checkpoint inhibitors (ICIs). The association between several variables and the therapeutic outcome of RD was determined via logistic regression analysis. RESULTS: Of the 288 patients, 225 (78.1%) received maintenance therapy and 108 (37.5%) received both ICI treatment for >180 days and maintenance therapy. All of 108 patients having ICIs for >180 days received maintenance therapy. Univariate analysis identified performance status, histology (adenocarcinoma), maintenance therapy, and ICI treatment >180 days as significant predictors of better progression-free survival (PFS) and overall survival (OS) after RD administration. Multivariate analysis confirmed that these factors independently predicted favorable PFS and OS. The therapeutic response and PD-L1 expression were not closely associated with outcome after RD treatment. In particular, maintenance therapy >4 cycles was more predictive of the better prognosis for RD treatment. CONCLUSION: Extended ICI treatment after chemoimmunotherapy and maintenance therapy enhanced the efficacy of second-line RD treatment in patients with advanced NSCLC.

Rapidly Growing Chest Wall Lipoma: Case Report and Calculating Volume Doubling Time.

Chest wall lipoma is a rare disease that might be asymptomatic and discovered incidentally. Chest wall lipomas are presumed to grow slowly, but no reports have evaluated the tumor volume doubling time (TVDT). The present study herein reports the case of a 35-year-old female patient with a relatively fast-growing chest wall lipoma. Lipomas have their characteristic shape and grow very slowly, so they are rarely completely resected, even though they are monitored and repeated imaging studies are performed. Homogeneous very low density, clear margins, and no invasion to the surrounding structure are characteristic finding on imaging, but some patients without these characteristics here have been reported here. As there has been no report of TVDT for chest wall lipoma, comparison was not possible, but TDVT for lipoma in this patient ranged from 235-412 days. Compared with reports that patients with non-small cell lung cancer showed TVDT of less than 450 days, TVDT in the patient described here did not appear to be slow. Accumulation of knowledge about this rare disease will help to elucidate it further.

EGFR Mutated Non-Small Cell Lung Cancer Complicated by Cancer Associated Ischemic Stroke.

We describe herein two patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) who developed cancer-associated ischemic stroke (CAIS), infarction caused by thromboembolism in the central nervous system. Case 1 was a 63-year-old man with Exon 19 deletion type EGFR mutated lung adenocarcinoma presenting with CAIS. Case 2 was a 71-year-old woman with Exon 21 L858R type EGFR mutated lung adenocarcinoma who developed CAIS during chemotherapy after EGFR-tyrosine kinase inhibitor (TKI) resistance. Although there was no recurrence of CAIS in these patients, anticancer therapy could be hampered by the comorbidity of CAIS. This can develop anytime from before clinical manifestations of NSCLC to the next treatment after EGFR-TKI resistance. The development of CAIS should be noted in patients with EGFR mutated NSCLC, who have a promising long-term prognosis. Anticancer and anticoagulant therapies as well as rehabilitation are important for patients who develop CAIS. Establishment of measurement tests to detect CAIS before onset is desired.

Impact of COVID-19 Pandemic on Advanced Non-small Cell Lung Cancer Treatment at a Japanese Hospital.

Background/Aim: The COVID-19 pandemic has forced medical institutions to scale back their practice. Changes in patient behavior seemed to be having an impact. We conducted a survey with the aim of reviewing lung cancer treatment during the pandemic period and identifying problems. Patients and Methods: We examined the medical records of all patients pathologically diagnosed with non-small cell lung cancer (NSCLC) in our hospital from 2017 to 2022. NSCLC patients were divided into two groups: those diagnosed between 2017 and 2019 (first period) and those diagnosed between 2020 and 2022 (second period). Results: Within the study period, 267 NSCLC patients (first period: 147 patients, second period: 121 patients) were diagnosed in our hospital. The patients in the two study periods did not differ significantly in age (p=0.613), ECOG performance status (p=0.125), and clinical stage (p=0.354). Tumor size was significantly larger in the second period with a mean of 5.88 cm ± 3.02, compared to 4.24 cm ± 1.76 in the first period (p<0.001). In the standard treatment group, the median survival time was 457 days in the first period and 313 days in the second period (p=0.063). In the best supportive care group, median survival time was 122 days in the first period and 57 days in the second period (p=0.004). Conclusion: Patients themselves refrained from seeking consultation for lung cancer treatment during the pandemic period. It is inconclusive how to reduce the delay due to the suppression of consultations, but this is an important issue for the future.

Using Compression Therapy to Treat Bilateral Lower Limb Edema in Patients with Lung Cancer: A Case Series.

ABSTRACT: Although rare, marked bilateral leg edema (BLE) can occur in patients with lung cancer. Systemic therapy for the underlying disease is important, but adjunct therapy might also be helpful. In this case series, the authors report on treating BLE in patients with lung cancer with compression therapy using elastic stockings and bandages. From April 2013 to March 2022, the authors conducted a retrospective survey of seven patients who developed marked BLE and received compression therapy. They evaluated effects based on improvements in subjective symptoms as well as objective findings 2 months after the start of the therapy. The bandage therapy was useful in patients who were driver-gene negative, but it was not effective in those who already had "progressive disease" with specific agents for their driver genes. No adverse events were observed. Compression therapy, even when attached or detached by nonmedical personnel, may provide favorable effects and should be considered as an adjunct treatment option in this population, in addition to effective systemic cancer therapy. These results indicate that a prospective clinical trial would be worthwhile.