Macroscopic qualitative evaluation of solid pancreatic lesion specimens from endoscopic ultrasound-guided fine needle aspiration/biopsies.

OBJECTIVES: To pathologically clarify the macroscopic features of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/B) specimens in representative pancreatic diseases and establish tissue-handling standards based on the macroscopic findings. METHODS: We gathered EUS-FNA/B specimens of cases at our institution with the final diagnoses of pancreatic ductal adenocarcinoma (PDAC, n = 172), neuroendocrine tumor (NET, n = 19), and chronic inflammatory lesion (CIL, n = 24) including autoimmune pancreatitis. We classified the specimens' macroscopic features in five categories (red strings, mixed-red-and-white strings, white cores, gray tissues, gelatinous tissues) and compared the specimens' features on cytological and histological slides. RESULTS: All five macroscopic categories were observed in variable combinations in the PDACs; red strings and white cores predominated in the NETs and CILs. White cores represented neoplastic (PDAC, NET) or lesion (CIL) tissues. Mixed-red-and-white strings were unique to PDACs and contained cancerous cells. Neoplastic cells were numerous in red strings in NETs but not the other groups. Gray and gelatinous tissues represented necrosis and mucin, respectively, and the former were almost exclusively observed in PDACs. Red strings, mixed-red-and-white strings, and white cores were suitable for histological examination, whereas gray and gelatinous tissues were suitable for cytological examination. The white cores, mixed-red-and-white strings, and gelatinous tissues may be composed of non-neoplastic tissues such as contaminated gastrointestinal epithelium. In seven PDACs, although white cores were obtained, a histological diagnosis was not established. CONCLUSIONS: Macroscopic evaluations of EUS-FNA/B can enable the identification of specimen components and a possible diagnosis. They also contribute to the selection of the optimal tissue-handling methods.

Elevated expression of endocan in the development of cervical squamous neoplasia of the uterus.

Accumulated evidence has shown that endocan, which was originally called endothelial cell-specific molecule-1, is an attractive prognostic factor in a variety of cancers. However, the relevance of endocan expression in human malignancies remains to be clarified. In the present study, the expression of endocan in cervical squamous neoplasia of the uterus, including low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), as well as in invasive squamous cell carcinoma was examined by immunohistochemistry. Endocan was not sufficiently expressed in the normal cervical epithelium. Endocan expression was present in LSIL cases but was limited to basal and parabasal areas of the cells. HSIL cases exhibited strong expression of endocan with widely distributed expression toward the epithelial surface. In contrast, further strong expression of endocan was not observed in patients with invasive carcinoma. This study is the first study showing increased expression of endocan in precancerous dysplastic lesions and malignancy of the cervix. The data suggest that a high expression level of endocan potentially contributes to the development of cervical squamous neoplasia of the uterus.

Increased alpha cell to beta cell ratio in patients with pancreatic cancer.

The development of pancreatic cancer (PC) is associated with worsening of glucose tolerance. However, there is limited information about the effects of PC on islet morphology. The aim of this study was to elucidate changes in alpha and beta cell mass in patients with PC. We enrolled 30 autopsy cases with death due to PC (9 with diabetes; DM) and 31 age- and BMI-matched autopsy cases without PC (controls, 12 with DM). Tumor-free pancreatic sections were stained for insulin and glucagon, and fractional beta cell (BCA) and alpha cell area (ACA) were quantified. In addition, expression of de-differentiation markers, i.e., ALDH1A3 and UCN3, was qualitatively evaluated. The pancreas of subjects with PC showed atrophic and fibrotic changes. There was no significant difference in BCA in subjects with PC compared to controls (1.53 ± 1.26% vs. 0.95 ± 0.42%, p = 0.07). However, ACA and ACA to BCA ratio were significantly higher in subjects with PC compared to controls (2.48 ± 2.39% vs. 0.53 ± 0.26% and 1.94 ± 1.93 vs. 0.59 ± 0.26, respectively, both p < 0.001). Increased ACA to BCA ratio was observed in subjects with PC irrespective of the presence of DM. Qualitative evaluation of ALDH1A3 and UCN3 expression showed no significant difference between the groups. In conclusion, in subjects with PC, alpha to beta cell mass ratio is increased, which may contribute to the increased risk of worsening glucose metabolism. Further studies are warranted to elucidate the mechanisms of increased alpha to beta cell mass in patients with PC.

Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by reduced beta cell mass (BCM). However, it remains uncertain whether the reduction in BCM in type 2 diabetes is due to a decrease in size or number of beta cells. Our aim was to examine the impact of beta cell size and number on islet morphology in humans with and without type 2 diabetes. METHODS: Pancreas samples were obtained from 64 Japanese adults with (n = 26) and without (n = 38) type 2 diabetes who underwent pancreatectomy. Using pancreatic tissues stained for insulin, we estimated beta cell size based on beta cell diameter. Beta cell number was estimated from the product of fractional beta cell area and pancreas volume divided by beta cell size. The associations of beta cell size and number with islet morphology and metabolic status were examined. RESULTS: Both beta cell size (548.7 ± 58.5 vs 606.7 ± 65.0 µm3, p < 0.01) and number (5.10 × 108 ± 2.35 × 108 vs 8.16 × 108 ± 4.27 × 108, p < 0.01) were decreased in participants with type 2 diabetes compared with those without diabetes, with the relative reduction in beta cell number (37%) being greater than for beta cell size (10%). Beta cell number but not size was positively correlated with BCM in participants with and without type 2 diabetes (r = 0.97 and r = 0.98, both p < 0.01) and negatively correlated with HbA1c (r = -0.45, p < 0.01). CONCLUSIONS/INTERPRETATION: Both beta cell size and number were reduced in participants with type 2 diabetes, with the relative reduction in beta cell number being greater. Decrease in beta cell number appears to be a major contributor to reduced BCM in type 2 diabetes.

Associations of birthweight and history of childhood obesity with beta cell mass in Japanese adults.

AIMS/HYPOTHESIS: Low birthweight is associated with a high risk of diabetes, but there are no reports discussing birthweight and pancreatic tissues in humans. The purpose of this study was to examine the correlation between birthweight and beta and alpha cell mass in humans. METHODS: Sixty-four Japanese adults with and without diabetes who underwent pancreatectomy and were able to recall their weight history including birthweight were included. Pancreatic tissues were stained for insulin and glucagon, and fractional beta cell area (BCA) and alpha cell area (ACA) were quantified. Islet size and density and beta cell replication were also quantified and their associations with birthweight were evaluated. RESULTS: In participants without diabetes, there was a weak positive correlation between birthweight and BCA (R = 0.34, p = 0.03). The group with a history of childhood obesity, but not the group with a history of obesity in adulthood only, showed higher BCA compared with those without a history of obesity (1.78 ± 0.74% vs 0.99 ± 0.53%, p = 0.01), and the correlation coefficient between birthweight and BCA increased after excluding those with a history of childhood obesity (R = 0.51, p < 0.01). In those with diabetes, there was no correlation between birthweight and BCA. No correlation was found between birthweight and ACA in either those with or without diabetes. CONCLUSIONS/INTERPRETATION: Birthweight and beta, but not alpha, cell mass are positively correlated in non-diabetic adults, and a history of childhood obesity may affect beta cell mass. Graphical abstract.

Intrahepatic Cholangiocarcinoma with High Microsatellite Instability and Tumor Mutation Burden That Responded Significantly to Pembrolizumab but Perforated within a Short Period.

Cholangiocarcinoma has a poor prognosis, and resection is the only curative treatment. Pembrolizumab, a programmed death receptor 1 inhibitor, has proven effective against unresectable or metastatic solid tumors with high microsatellite instability (MSI-H) or a high tumor mutation burden (TMB-H). In the present case, pembrolizumab treatment was initiated after standard chemotherapy for MSI-H and TMB-H unresectable intrahepatic cholangiocarcinoma. Intrahepatic tumor necrosis perforated the abdominal cavity. Emergency surgery was performed, but the patient died 36 days after admission. A pathological autopsy revealed that the intrahepatic tumor had almost completely disappeared.

A Retrospective Study of the Clinical, Radiological, and Pathological Characteristics of Patients with Interstitial Pneumonia Preceding Rheumatoid Arthritis.

Objective Interstitial lung disease (ILD) is the most critical manifestation in patients with rheumatoid arthritis (RA). In some cases, ILD may appear before the RA onset. Some patients with an initial diagnosis of idiopathic interstitial pneumonia (IIPs) develop RA; however, few studies have reported on its features, and the details remain unknown. In the present study, the clinical, radiological, and pathological features were evaluated in patients with ILD preceding RA. Methods The clinical, radiological, and pathological features of patients with ILD preceding RA were retrospectively reviewed using the medical records. Patients Ten patients with ILD preceding RA out of 883 IIP patients who underwent a surgical lung biopsy at our hospital from 2004 to 2018 were retrospectively examined. Results The median patient age was 59 (range 50-76) years old, and 7 of the patients were women. The median time from the ILD diagnosis to the RA onset was 50 (range 33-65) months. Regarding the high-resolution computed tomography pattern, the "indeterminate for UIP" pattern was the most popular, and cysts were seen in all cases. Attenuation around the cyst was prominent. Pathological findings showed plasma cell infiltration, bronchus-associated lymphoid tissue (BALT), and bronchiolitis in the lobules. Cellular and destructive bronchiolitis was noticeable in many patients with ILD preceding RA and contributed to the destruction and dilation of the bronchiole. Conclusion In ILD patients with IIP, radiological and pathological findings with increased attenuation around the cysts, prominent inflammatory cell infiltration (especially in plasma cells), an increase in the BALT number, and cellular and destructive bronchiolitis might serve as helpful RA development indicators.

Hereditary diffuse gastric cancer in a Japanese family with CDH1 mutation three case reports.

BACKGROUND: Germline pathogenic variants in the E-cadherin gene CDH1 cause hereditary diffuse gastric cancer (HDGC), which is an autosomal dominant cancer syndrome, accounting for 1-3% of all gastric cancers. HDGC harboring a CDH 1 variant is extremely rare in Japan. METHOD: In this study we report the clinical courses of three cases with HDGC from a single Japanese family. RESULTS: The proband exhibited advanced and metastatic gastric cancer, and was found to have a previously reported heterozygous frameshift variant in CDH1 (NM_004360.3:c.1009_1010del:p.Ser337Phefs*12). Five at-risk relatives underwent presymptomatic molecular testing after careful genetic counseling, and three were molecularly diagnosed as positive for the variant. Esophagogastroduodenoscopy was performed in these relatives revealing abnormal small pale mucosal patches, small ulcerative lesion and no abnormal findings. Moreover, random and targeted biopsies were compatible with pathological diagnosis of HDGC in the three cases, all of which underwent total prophylactic gastrectomy. CONCLUSION: It is critical for the assessment and management of HDGC patients to be actively offered a multidisciplinary and familial-oriented approach. Notably, genetic screening in suspected individuals and familial members is a determining piece for a higher detection rate and the identification of clinical relevant mutations in both low and high-incidence gastric cancer countries.

Diagnostic and prognostic biomarkers for progressive fibrosing interstitial lung disease.

No biomarkers have been identified in bronchoalveolar lavage fluid (BALF) for predicting fibrosis progression or prognosis in progressive fibrosing interstitial lung disease (PF-ILD). We investigated BALF biomarkers for PF-ILD diagnosis and prognosis assessment. Overall, 120 patients with interstitial pneumonia who could be diagnosed with PF-ILD or non PF-ILD were enrolled in this retrospective study. PF-ILD was diagnosed according to Cottin's definition. All patients underwent bronchoscopy and BALF collection. We evaluated blood and BALF parameters, high-resolution computed tomography (HRCT) patterns, and spirometry data to identify factors influencing PF-ILD diagnosis and prognosis. On univariate logistic analysis, age, sex, the BALF white blood cell fraction (neutrophil, lymphocyte, eosinophil, and neutrophil-to-lymphocyte ratio), BALF flow cytometric analysis (CD8), and an idiopathic pulmonary fibrosis/usual interstitial pneumonia pattern on HRCT were correlated with PF-ILD diagnosis. Multivariate logistic regression analysis revealed that sex (male), age (cut-off 62 years, area under the curve [AUC] 0.67; sensitivity 0.80; specificity 0.47), white blood cell fraction in BALF (NLR, neutrophil, and lymphocyte), and CD8 in BALF (cut-off 34.2; AUC 0.66; sensitivity, 0.74; specificity, 0.62) were independent diagnostic predictors for PF-ILD. In BALF, the NLR (cut-off 8.70, AUC 0.62; sensitivity 0.62; specificity 0.70), neutrophil count (cut-off 3.0, AUC 0.59; sensitivity 0.57; specificity 0.63), and lymphocyte count (cut-off 42.0, AUC 0.63; sensitivity 0.77; specificity 0.53) were independent diagnostic predictors. In PF-ILD patients (n = 77), lactate dehydrogenase (cut-off 275, AUC 0.69; sensitivity 0.57; specificity 0.78), Krebs von den Lungen-6 (cut-off 1,140, AUC 0.74; sensitivity 0.71; specificity 0.76), baseline forced vital capacity (FVC) (cut-off 1.75 L, AUC 0.71; sensitivity, 0.93; specificity, 0.46), and BALF neutrophil ratio (cut-off 6.0, AUC 0.72; sensitivity 0.79; specificity 0.80) correlated with death within 3 years. The BALF cellular ratio, particularly the neutrophil ratio, correlated with the diagnosis and prognosis of PF-ILD. These findings may be useful in the management of patients with interstitial pneumonia.

Delayed Detection of Hydrocephalus following Mildly Traumatic Subarachnoid Hemorrhage in Corticobasal Degeneration: A Case Report.

A 65-year-old woman presented with slowly progressive aphasia with gait disturbance associated with parkinsonism. She experienced a fall that resulted in a brain trauma. Brain imaging revealed a small amount of subarachnoid hemorrhage (SAH) with intraventricular bleeding. Despite conservative therapy, gait disturbance and hyporesponsiveness gradually deteriorated following that brain trauma. One month later, she was transferred to our hospital, and magnetic resonance imaging revealed prominent communicating hydrocephalus. A ventriculoperitoneal shunt and brain biopsy were performed. Neurosurgical intervention did not improve the patient's neurological condition. Clinical-pathological analysis confirmed the diagnosis of corticobasal degeneration (CBD) as an underlying disease relating to parkinsonism and aphasia. In patients with parkinsonism with high risks of falling, attention should be paid to neurological deterioration due to traumatic SAH-related hydrocephalus. Particularly, in patients with aphasia such as in those with CBD, delayed detection of posttraumatic complications might cause poor responsiveness to surgical intervention.

Clinical characteristics of COVID-19 patients with underlying rheumatic diseases in Japan: data from a multicenter observational study using the COVID-19 Global Rheumatology Alliance physician-reported registry.

INTRODUCTION: To describe clinical characteristics of patients in Japan with coronavirus disease 19 (COVID-19) and pre-existing rheumatic disease and examine the possible risk factors associated with severe COVID-19. METHODS: Adults with rheumatic disease and a COVID-19 diagnosis who were registered in the COVID-19 Global Rheumatology Alliance (C19-GRA) physician-reported registry from Japan between 15 May 2020 and 12 May 2021 were included. Multivariable logistic regression models were used to assess factors associated with severe COVID-19 progression, defined as death or requiring oxygen inhalation. RESULTS: In total, 222 patients were included in the study. Rheumatoid arthritis (48.2%), gout (14.4%), and systemic lupus erythematosus (8.1%) were the most common types of rheumatic disease, 55.1% of patients were in remission and 66.2% had comorbid disease. Most patients were hospitalised (86.9%) for COVID-19, 43.3% received oxygen, and 9.0% died. Older age (≥ 65 years), corticosteroid use, comorbid diabetes, and lung diseases are associated with higher risk for severe COVID-19 progression (odds ratio (OR) 3.52 [95% confidence interval (CI) 1.69-7.33], OR 2.68 [95% CI 1.23-5.83], OR 3.56 [95% CI 1.42-8.88], and OR 2.59 [95% CI 1.10-6.09], respectively). CONCLUSIONS: This study described clinical characteristics of COVID-19 patients with rheumatic diseases in Japan. Several possible risk factors for severe COVID-19 progression were suggested. Key points • Clinical characteristics of 222 adult patients in Japan with coronavirus disease 19 (COVID-19) and pre-existing rheumatic diseases were described. • Most patients were hospitalised (86.9%) for COVID-19 in Japan, 43.3% received oxygen, and 9.0% died. • The COVID-19 characteristics of patients with rheumatic diseases did not show any obvious different pattern from those of the general population in Japan. • In this study, older age (≥ 65 years), corticosteroid use, comorbid diabetes, and lung diseases are associated with higher risk for severe COVID-19 progression.

Immunomodulatory Cell Therapy Using αGalCer-Pulsed Dendritic Cells Ameliorates Heart Failure in a Murine Dilated Cardiomyopathy Model.

BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening disease, resulting in refractory heart failure. An immune disorder underlies the pathophysiology associated with heart failure progression. Invariant natural killer T (iNKT) cell activation is a prospective therapeutic strategy for ischemic heart disease. However, its efficacy in nonischemic cardiomyopathy, such as DCM, remains to be elucidated, and the feasible modality for iNKT cell activation in humans is yet to be validated. METHODS: Dendritic cells isolated from human volunteers were pulsed with α-galactosylceramide ex vivo, which were used as α-galactosylceramide-pulsed dendritic cells (αGCDCs). We treated DCM mice harboring mutated troponin TΔK210/ΔK210 with αGCDCs and evaluated the efficacy of iNKT cell activation on heart failure in DCM mice. Furthermore, we investigated the molecular basis underlying its therapeutic effects in these mice and analyzed primary cardiac cells under iNKT cell-secreted cytokines. RESULTS: The number of iNKT cells in the spleens of DCM mice was reduced compared with that in wild-type mice, whereas αGCDC treatment activated iNKT cells, prolonged survival of DCM mice, and prevented decline in the left ventricular ejection fraction for 4 weeks, accompanied by suppressed interstitial fibrosis. Mechanistically, αGCDC treatment suppressed TGF (transforming growth factor)-ß signaling and expression of fibrotic genes and restored vasculature that was impaired in DCM hearts by upregulating angiopoietin 1 (Angpt1) expression. Consistently, IFNγ (interferon gamma) suppressed TGF-ß-induced Smad2/3 signaling and the expression of fibrotic genes in cardiac fibroblasts and upregulated Angpt1 expression in cardiomyocytes via Stat1. CONCLUSIONS: Immunomodulatory cell therapy with αGCDCs is a novel therapeutic strategy for heart failure in DCM.

Association of visit-to-visit glycemic variability with risk of cardiovascular diseases in high-risk Japanese patients with type 2 diabetes: A subanalysis of the EMPATHY trial.

AIMS/INTRODUCTION: Long-term glycemic variability is important for predicting diabetic complications, but evaluation in a Japanese population is lacking. The aim of this study was to explore the relationship between visit-to-visit glycemic variability (VVV) and cardiovascular diseases (CV) in Japanese patients with type 2 diabetes, using the prospective cohort of the EMPATHY trial. MATERIALS AND METHODS: Among 4532 participants with at least three HbA1c measurements, VVV was defined using the coefficient of variation (CV-HbA1c). The outcomes were the composite cardiovascular endpoints, including cardiac, cerebral, renal, and vascular events. The odds ratios (ORs) for the development of outcomes were estimated by using logistic regression models. RESULTS: During a median follow-up of 38 months, 190 subjects developed CV events. The risk of developing CV events increased significantly with increasing quintile of CV-HbA1c, after multivariable adjustment including the mean-HbA1c (OR for the fifth vs first quintile, 1.73; 95%CI, 1.03-2.91; P for trend test = 0.003). There was a stronger association between CV-HbA1c and CV events in patients with a mean-HbA1c of <7% compared with those with a mean-HbA1c of ≥7% (OR per 1 standard deviation, 1.51; 95%CI, 1.23-1.85 and 1.13; 95%CI, 0.98-1.29, respectively; P for interaction = 0.02). CONCLUSIONS: Increases of VVV were associated with the risk of CV events in Japanese patients with type 2 diabetes independent of the mean-HbA1c. The long-term variability of HbA1c as well as the mean HbA1c might be an important glycemic indicator in the management of patients with type 2 diabetes, especially in those with a mean-HbA1c of <7%.

Successful treatment with afatinib following the failure of osimertinib rechallenge with osimertinib-induced interstitial lung disease: A case report.

Herein, we report the case of an 84-year-old woman with epidermal growth factor receptor (EGFR) mutation exon 19 deletion postoperative recurrent lung adenocarcinoma. Osimertinib was administered as a first-line treatment; however, she was urgently admitted to our hospital due to dyspnea on the 46th day. Chest computed tomography revealed bilateral diffuse ground-glass opacities (GGOs) suggestive of grade 3 osimertinib-induced interstitial lung disease (ILD). After discontinuation of osimertinib in combination with short-term corticosteroid therapy, widespread GGOs were promptly resolved. As the disease gradually deteriorated after discontinuation of osimertinib, we administered osimertinib (80 mg every other day) followed by careful observation. However, bilateral GGOs re-appeared on the 15th day, and the diagnosis of osimertinib-induced ILD was established. After the improvement in ILD following corticosteroid therapy, afatinib was administered as salvage therapy, resulting in desirable control of lung cancer without any relapse of ILD. Our results indicate that afatinib would be a promising alternative treatment option even in patients who develop osimertinib-induced ILD and experience failure of osimertinib rechallenge.

Excessive Hypoxia-Inducible Factor-1α Expression Induces Cardiac Rupture via p53-Dependent Apoptosis After Myocardial Infarction.

Background Apoptosis plays a pivotal role in cardiac rupture after myocardial infarction (MI), and p53 is a key molecule in apoptosis during cardiac rupture. Hif-1α (hypoxia-inducible factor-1α), upregulated under hypoxia, is a known p53 inducer. However, the role of Hif-1α in the regulatory mechanisms underlying p53 upregulation, apoptosis, and cardiac rupture after MI is unclear. Methods and Results We induced MI in mice by ligating the left anterior descending artery. Hif-1α and p53 expressions were upregulated in the border zone at day 5 after MI, accompanied by apoptosis. In rat neonatal cardiomyocytes, treatment with cobalt chloride (500 µmol/L), which mimics severe hypoxia by inhibiting PHD (prolyl hydroxylase domain-containing protein), increased Hif-1α and p53, accompanied by myocyte death with caspase-3 cleavage. Silencing Hif-1α or p53 inhibited caspase-3 cleavage, and completely prevented myocyte death under PHD inhibition. In cardiac-specific Hif-1α hetero-knockout mice, expression of p53 and cleavage of caspase-3 and poly (ADP-ribose) polymerase were reduced, and apoptosis was suppressed on day 5. Furthermore, the cleavage of caspase-8 and IL-1ß (interleukin-1ß) was also suppressed in hetero knockout mice, accompanied by reduced macrophage infiltration and matrix metalloproteinase/tissue inhibitor of metalloproteinase activation. Although there was no intergroup difference in infarct size, the cardiac rupture and survival rates were significantly improved in the hetero knockout mice until day 10 after MI. Conclusions Hif-1α plays a pivotal role in apoptosis, inflammation, and cardiac rupture after MI, in which p53 is a critical mediator, and may be a prospective therapeutic target for preventing cardiac rupture.

A case of intrathoracic desmoid tumor with pulmonary Mycobacterium abscessus disease.

A 68-year-old man who was on treatment for pulmonary Mycobacterium avium complex complained a worsening of sputum. Although he archived negative sputum culture two months ago, sputum culture tests revealed the newly isolation of Mycobacterium abscessus repeatedly. Chest computed tomography showed newly-appeared extra-pulmonary mass lesion in contact with a cyst at the bottom of his right lung. From the results of contrast-enhanced magnetic resonance imaging, we first suspected loculated pleural effusion due to Mycobacterium abscessus infection. A thoracoscopic examination was performed as the right pneumothorax developed, and the pleural lesion was successfully resected and diagnosed as an intrathoracic desmoid tumor. Intrathoracic desmoid tumor is very rare, and this is the first report of a case with pulmonary Mycobacterium abscessus disease.

Correction to: Ultra-high-resolution computed tomography can demonstrate alveolar collapse in novel coronavirus (COVID-19) pneumonia.

The correct caption is given below.

Ultra-high-resolution computed tomography can demonstrate alveolar collapse in novel coronavirus (COVID-19) pneumonia.

PURPOSE: To review the chest computed tomography (CT) findings on the ultra-high-resolution CT (U-HRCT) in patients with the Novel coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: In February 2020, six consecutive patients with COVID-19 pneumonia (median age, 69 years) underwent U-HR CT imaging. U-HR-CT has a larger matrix size of 1024 × 1024 thinner slice thickness of 0.25 mm and can demonstrate terminal bronchioles in the normal lungs; as a result, Reid's secondary lobules and their abnormalities can be identified. The distribution and hallmarks (ground-glass opacity, consolidation with or without architectural distortion, linear opacity, crazy paving) of the lung opacities on U-HRCT were visually evaluated on a 1 K monitor by two experienced reviewers. The CT lung volume was measured, and the ratio of the measured lung volume to the predicted total lung capacity (predTLC) based on sex, age and height was calculated. RESULTS: All cases showed crazy paving pattern in U-HRCT. In these lesions, the secondary lobules were smaller than those in the un-affected lungs. CT lung volume decreased in two cases comparing predTLC. CONCLUSION: U-HRCT can evaluate not only the distribution and hallmarks of COVID-19 pneumonia but also visualize local lung volume loss.

Five cases of BRAF V600E-mutant lung adenocarcinoma with high expression of programmed death ligand 1.

We reported consecutive five patients with BRAF V600E-mutant recurrent or advanced non-small cell lung cancer who were identified between April 2016 and June 2019. All five patients had high programmed death ligand 1 (PD-L1) tumor proportion scores (50, 55, 75, 95 and 100%). Four of the five patients received regimens including pembrolizumab. Of them, one patient experienced a partial response, but two patients experienced progressive disease and one patient was not evaluable. Three of the four patients received regimens including pemetrexed were able to continue long-term treatment. The presence of a BRAF mutation may be associated with higher levels of PD-L1 expression. The effect of immune checkpoint inhibitors therapy in patients with BRAF mutation was similar to the previous reports in patients with previously treated advanced non-small cell lung cancer with PD-L1 tumor proportion score ≥50%. Chemotherapy regimens including pemetrexed may have a positive effect in patients with BRAF V600E-mutant lung adenocarcinoma. Accumulation of additional Case series is necessary to confirm our results.

A rapid assessment of the political economy of health at district level, with a focus on maternal, newborn and child health, in Bangladesh, Indonesia, Nepal and the Philippines.

Low- and middle-income countries (LMICs) face many challenges and competing demands in the health sector, including maternal and newborn mortality. The allocation of financial and human resources for maximum health impact is important for social and economic development. Governments must prioritize carefully and allocate scarce resources to maximum effect, but also in ways that are politically acceptable, financially and institutionally feasible, and sustainable. Political economy analysis (PEA)-that gets what, when and why-can help explain that prioritization process. We used PEA to investigate how four Asian LMICs (Bangladesh, Indonesia, Nepal and the Philippines) allocate and utilize resources for maternal, newborn and child health (MNCH). Using mixed research methods including a literature review, field interviews at national and sub-national level, and policy, process and budget analysis in each country, we examined three political economy issues: (1) do these countries demonstrably prioritize MNCH at policy level; (2) if so, is this reflected in the allocation of financial and other resources and (3) if resources are allocated to MNCH, do they achieve the intended outputs and outcomes through actual programme implementation? We also considered the influence of transnational developments. We found that all four countries demonstrate political commitment to health, including MNCH. However, the health sector receives comparatively low public financing, governments often do not follow through on plans or pronouncements, and capacity for related action varies widely. Poor governance and decentralization, lack of data for monitoring and evaluation of progress, and weak public sector human resource capacity were frequent problems; engagement of the private or non-government sectors is an important consideration. Opportunities exist to greatly improve equity and MNCH outcomes in these nations, using a mix of evidence, improved governance, social engagement and the media to influence decisions, increase resource allocation to and improve accountability in the health sector.