An algorithm-based technique for counting mitochondria in cells using immunohistochemical staining of formalin-fixed and paraffin-embedded sections.

PURPOSE: Visualizing mitochondria in cancer cells from human pathological specimens may improve our understanding of cancer biology. However, using immunohistochemistry to evaluate mitochondria remains difficult because almost all cells contain mitochondria and the number of mitochondria per cell may have important effects on mitochondrial function. Herein, we established an objective system (Mito-score) for evaluating mitochondria using machine-based processing of hue, saturation, and value color spaces. METHODS: The Mito-score was defined as the number of COX4 (mitochondrial inner membrane) immunohistochemistry-positive pixels divided by the number of nuclei per cell. The system was validated using four lung cancer cell lines, normal tissues, and lung cancer tissues (199 cases). RESULTS: The Mito-score correlated with MitoTracker, a fluorescent dye used to selectively label and visualize mitochondria within cells under a microscope (R2 = 0.68) and with the number of mitochondria counted using electron microscopy (R2 = 0.79). Histologically, the Mito-score of small cell carcinoma (57.25) was significantly lower than that of adenocarcinoma (147.5, p < 0.0001), squamous cell carcinoma (120.6, p = 0.0004), and large cell neuroendocrine carcinoma (111.8, p = 0.002). CONCLUSION: The Mito-score method enables the analysis of the mitochondrial status of human formalin-fixed paraffin-embedded specimens and may provide insights into the metabolic status of cancer.

CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade.

Serine/threonine kinase, cell division cycle 7 (CDC7) is critical for initiating DNA replication. TAK-931 is a specific CDC7 inhibitor, which is a next-generation replication stress (RS) inducer. This study preclinically investigates TAK-931 antitumor efficacy and immunity regulation. TAK-931 induce RS, generating senescence-like aneuploid cells, which highly expressed inflammatory cytokines and chemokines (senescence-associated secretory phenotype, SASP). In vivo multilayer-omics analyses in gene expression panel, immune panel, immunohistochemistry, RNA sequencing, and single-cell RNA sequencing reveal that the RS-mediated aneuploid cells generated by TAK-931 intensively activate inflammatory-related and senescence-associated pathways, resulting in accumulation of tumor-infiltrating immune cells and potent antitumor immunity and efficacy. Finally, the combination of TAK-931 and immune checkpoint inhibitors profoundly enhance antiproliferative activities. These findings suggest that TAK-931 has therapeutic antitumor properties and improved clinical benefits in combination with conventional immunotherapy.

Integrative Systematics and Biogeography of the Hydrozoans (Leptothecata: Eirenidae) Eirene menoni Kramp, 1953 and Eirene lacteoides Kubota and Horita, 1992 from Japan and China with Comments on Pacific Ocean Distributions.

The hydrozoan family Eirenidae is known scientifically for its morphological plasticity and challenges in species identification. We used an integrative taxonomic approach based on morphological, molecular and life history evidence to systematically assess field-collected medusae of Eirene menoni Kramp 1953 and captive raised polyps of both E. menoni and E. lacteoides Kubota and Horita 1992. Following morphological review, we updated the genus description to include the presence of rudimentary bulbs (warts) on the ring canal in at least eight of the 24 valid Eirene species. We propose the potential for the mature E. menoni hydrotheca to develop into a gonotheca. However, this proposal will require additional study for verification. We provide validated distribution records from the Indo-Pacific Ocean for E. menoni,and updated collection records for E. lacteoides from the Yellow and East China Seas, and public aquaria-cultured specimens from Japan and Hawaii, using cytochrome c oxidase I (COI) sequences that we generated and compared with those from GenBank. The COI gene reliably separated four species, each forming a monophyletic clade with strong bootstrap support and low mean intraspecific molecular divergences (≤ 1%) within clades. However, some of the deeper nodes of the tree remained poorly resolved, and our analysis failed to demonstrate monophyly among eirenid genera Eirene and Tima. Our integrative taxonomic approach is essential in confirming species identity within the family Eirenidae and genus Eirene,and we have also identified a likely range expansion of E. lacteoides to Hawaii.

Effectiveness of Albumin-Fused Thioredoxin against 6-Hydroxydopamine-Induced Neurotoxicity In Vitro.

Parkinson's disease (PD) is a neurodegenerative disorder caused by oxidative stress-dependent loss of dopaminergic neurons in the substantia nigra and elevated microglial inflammatory responses. Recent studies show that cell loss also occurs in the hypothalamus in PD. However, effective treatments for the disorder are lacking. Thioredoxin is the major protein disulfide reductase in vivo. We previously synthesized an albumin-thioredoxin fusion protein (Alb-Trx), which has a longer plasma half-life than thioredoxin, and reported its effectiveness in the treatment of respiratory and renal diseases. Moreover, we reported that the fusion protein inhibits trace metal-dependent cell death in cerebrovascular dementia. Here, we investigated the effectiveness of Alb-Trx against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro. Alb-Trx significantly inhibited 6-OHDA-induced neuronal cell death and the integrated stress response. Alb-Trx also markedly inhibited 6-OHDA-induced reactive oxygen species (ROS) production, at a concentration similar to that inhibiting cell death. Exposure to 6-OHDA perturbed the mitogen-activated protein kinase pathway, with increased phosphorylated Jun N-terminal kinase and decreased phosphorylated extracellular signal-regulated kinase levels. Alb-Trx pretreatment ameliorated these changes. Furthermore, Alb-Trx suppressed 6-OHDA-induced neuroinflammatory responses by inhibiting NF-κB activation. These findings suggest that Alb-Trx reduces neuronal cell death and neuroinflammatory responses by ameliorating ROS-mediated disruptions in intracellular signaling pathways. Thus, Alb-Trx may have potential as a novel therapeutic agent for PD.

Factors predicting oral and maxillofacial fractures after falling and factors predicting the duration of treatment.

BACKGROUND/AIM: The first objective of this study was to identify predictive factors for oral and maxillofacial fractures at the initial response to the patient. The second objective was to determine the factors influencing the incidence of treatment duration of more than 1 month using the information shown in the medical record. MATERIALS AND METHODS: Hospital records from 2011 to 2019 were reviewed to identify patients who had sustained oral and maxillofacial injuries by falling or falling from a height. Patterns and types of oral and maxillofacial injury, injury severity, and background of the injury were collected from the hospital records. The variables independently associated with a treatment duration of more than 1 month were determined by logistic regression analysis. RESULTS: In total, 282 patients (150 men, 132 women; median age, 17.5 years) were selected for analysis. Maxillofacial fractures were observed in 20.9% of patients (59/282); among these, mandibular fractures were the most common (47/59). Logistic regression analysis showed that age (odds ratio [OR], 1.026), nighttime occurrence (OR, 2.192), and upper face injury (OR, 20.704) were independent predictive factors for having a maxillofacial fracture. Additionally, the number of injured teeth (OR, 1.515) and the use of intermaxillary fixation (OR, 16.091) were independent predictors of treatment duration of more than 1 month. CONCLUSIONS: These results may be useful in the initial management of maxillofacial injuries in terms of better-informing patients injured by falling their expected treatment duration and managing the psychological impacts of a long treatment duration.

Analysis of micrognathia with obstructive sleep apnea syndrome improved by a combination of Le Fort I with horseshoe osteotomies, mandibular distraction osteogenesis, and genioplasty.

The relationship between microgenia and obstructive sleep apnea syndrome is well known. 27-year-old woman. She underwent a combination of Le Fort I with horseshoe osteotomies and mandibular distraction osteogenesis and genioplasty. She was satisfied with the aesthetics of her face, with an AHI of 7.8/h.

Bone marrow-derived vasculogenesis leads to scarless regeneration in deep wounds with periosteal defects.

Deep skin wounds with periosteal defects, frequently caused by traffic accidents or radical dissection, are refractory. Transplant surgery is frequently performed, but patients are subjected to stress for long operation periods, the sacrifice of donor regions, or several complications, such as flap necrosis or intractable ulcers. Even if the defects are covered, a scar composed of fibrous tissue remains in the body, which can cause itching, dysesthesia, or repeated ulcers because of the lack of distribution of peripheral nerves or hair follicles. Thus, treatments with the aim of regenerating lost tissue for deep wounds with periosteal defects are needed. Here, we show that the use of gelatin sponges (GS), which have been used as haemostatic materials in clinical practice, allowed the regeneration of heterogeneous tissues, including periosteum, skin, and skin appendages, when used as scaffolds in deep wounds with periosteal defects in rats. Bone marrow transplantation in rats revealed the mechanism by which the microenvironment provided by GS enabled bone marrow-derived cells (BMDCs) to form a vascular niche, followed by regeneration of the periosteum, skin, or skin appendages such as hair follicles by local cells. Our findings demonstrated that vascular niche formation provided by BMDCs is crucial for heterogeneous tissue regeneration.

Octorhopalona saltatrix, a New Genus and Species (Hydrozoa, Anthoathecata) from Japanese Waters

Approximately 300 species of cnidarian jellyfish have been reported in Japanese waters. However, many specimens remain unidentified. In this study, taxonomic investigations, including morphological observations and molecular 16S phylogenetic analyses, were conducted on unknown specimens collected off Oarai, Sagami Bay, and Tosa Bay, Japan. The specimens have the following morphological characteristics: distinct peaks in jelly above the base of the manubrium, a red band on the manubrium, and cylindrical marginal bulbs, each with an abaxial ocellus that is common to the family Halimedusidae. However, the specimens can be distinguished from other Halimedusidae species by their eight radial canals, eight tentacles with numerous stalked nematocyst knobs, and eight nematocyst tracks on the exumbrella. Moreover, molecular phylogenetic analyses revealed that the Kimura two-parameter distance between the specimens and other Halimedusa species was 0.066-0.099, which is considered to represent intergeneric variability. Based on this result, we described it as a new species and established a new genus for taxonomic stabilization. We also emended the diagnostic characters of the family Halimedusidae owing to the establishment of the new genus. Halimedusidae comprises five species in four genera. This paper provides taxonomic keys for the identification of species in the family Halimedusidae.

Use of bronchoalveolar lavage in diagnosing angioimmunoblastic T-cell lymphoma: A case report.

Angioimmunoblastic T-cell lymphoma (AITL) is a type of peripheral T-cell tumour that belongs to the group of non-Hodgkin's lymphomas. Pulmonary lesions can be found in 7%-10% of AITL cases. Imaging findings of the lungs varied; however, immunoblastic infiltration in the lungs is rare. Our patient was a 73-year-old man who received repeated chemotherapy for AITL. Fourth-line therapy using romidepsin controlled the illness, but the patient was hospitalized for dyspnoea and an infiltrative shadow. We performed bronchoalveolar lavage (BAL), and the culture was positive for Haemophilus influenzae. The patient was initially discharged with antibiotic therapy, but hospitalized again. Antibiotics were ineffective and the patient required mechanical ventilation. BAL was performed again, after which fluid cytology revealed immunoblast-like atypical cells. Therefore, the patient was diagnosed with pulmonary infiltration due to AITL. Steroid therapy proved ineffective, and the patient died. BAL was used to effectively diagnose pulmonary AITL infiltration.

Comparison of the wound-healing efficacy of gelatin sponge dressings and that of artificial dermis using atelocollagen in a rat cranial periosteal defect model.

In oral surgery, tissue loss may occur in some cases, resulting in bone exposure and subsequent wound infection and possible scar formation during secondary healing. In this study, Terudermis® Artificial Dermis (AD-T), a dermal defect graft made from processed bovine dermis collagen and gelatin sponge (GS) were used as dressings on 100-mm2 wounds with exposed bone on the heads of rats. For the control group, the wound was left exposed. The wound-healing efficacy of the treatment was compared macroscopically and histologically among the three groups at 1, 2, and 4 weeks after surgery. Complete wound healing was achieved faster in the AD-T group than in the GS group, and osteoblasts appeared on the bone surface, indicating accelerated bone remodeling. Furthermore, in the AD-T group, there was an increased production of newly formed blood vessels, fibroblasts and osteoblasts positive for anti-cortactin antibodies, which are believed to contribute to wound healing. Our findings suggest that AD-T is better than GS as a wound dressing material.

First-line osimertinib in elderly patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer: a retrospective multicenter study (HOT2002).

Osimertinib is a standard of care therapy for previously untreated epidermal growth factor receptor mutation-positive non-small cell lung cancer. However, limited data exist regarding the efficacy and safety of osimertinib as a first-line therapy for elderly patients aged 75 years or older. To assess the potential clinical benefits of osimertinib in this population, this retrospective multi-institutional observational study included 132 patients with non-small cell lung cancer (age ≥ 75 years), who received osimertinib as first-line treatment. The proportion of patients with 1-year progression-free survival was 65.8% (95% confidence interval 57.1-73.5). The median progression-free survival was 19.4 (95% confidence interval 15.9-23.9) months. The median overall survival was not reached (95% confidence interval 24.6-not reached). The frequency of pneumonitis was 17.4%, with a grade 3 or higher rate of 9.1%. More than two-thirds of treatment discontinuations due to pneumonitis occurred within 3 months of starting osimertinib, and the prognosis of patients with pneumonitis was unsatisfactory. Osimertinib is one of the effective first-line therapeutic options for patients aged 75 years or older; however, special caution should be exercised due to the potential development of pneumonitis.

Tima nigroannulata (Cnidaria: Hydrozoa: Eirenidae), a New Species of Hydrozoan from Japan.

Tima nigroannulata sp. nov. is described from medusae collected in shallow waters of four prefectures on the Pacific coast of Japan (Miyagi, Fukushima, Kanagawa, and Miyazaki), as well as from cultures maintained at two aquaria (Enoshima Aquarium, Kanagawa Prefecture; Tsuruoka City Kamo Aquarium, Yamagata Prefecture). Adult medusae differ from those of other known species of the genus Tima Eschscholtz, 1829 in the following combination of characters: (1) umbrella usually hemispherical or higher, (2) marginal tentacles up to 50 or more in number; and (3) black pigment granules form a ring around the umbrella rim, and sometimes extend onto the tentacles and radial canals. Their hydroids, from aquarium cultures, have stolonal colonies with pedicels of varied length, vestigial hydrothecae, slender and vase- to club-shaped hydranths, and a whorl of about 20 filiform tentacles with an intertentacular web basally. Medusa buds develop singly within gonothecae that arise from the hydrothecal pedicels. The cnidomes of both hydroid and medusa stages comprise heteronemes, provisionally identified as microbasic mastigophores. Medusae of T. nigroannulata are confirmed as a unique, cohesive lineage by comparing mtDNA COI sequence fragments with those from two congeners, resulting in three well-supported reciprocally monophyletic clades, one representing each species. Records of the western Atlantic medusa Tima formosa L. Agassiz, 1862 from Japan overlap those of T. nigroannulata, and are believed to have been based on the new species described herein.

Successful rechallenge with cetuximab after progression with nivolumab for recurrent cervical lymph node metastasis from carcinoma of the tongue.

We can infer that the immunostimulatory effect of nivolumab and reactivation of cetuximab enhance the antitumor effect of the therapy.

Differences in the Knowledge and Experience of Physicians and Dentists About Medication-Related Osteonecrosis of the Jaw in Osteoporotic Patients.

AIM: Prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis requires the cooperation of physicians and dentists. We investigated the knowledge, experience, and behaviour related to medical and dental cooperation for MRONJ prevention in patients with osteoporosis between physicians and dentists practising in the Shiga prefecture. MATERIALS AND METHODS: We conducted a cross-sectional study to investigate the cooperation between practising physicians and dentists for preventing osteonecrosis of the jaw (ONJ) in patients with osteoporosis using 2 separate questionnaires from July 28, 2018, to February 3, 2019. RESULTS: Of 461 dentists who were sent the questionnaires at their dental clinics, 307 (67%) responded via fax. Of 846 physicians who were sent the questionnaire at their clinics, 378 (45%) responded via fax. Of these, 268 (32%) were finally analysed because 110 (13%) physicians had never treated patients with osteoporosis; 50% dentists and 24% physicians were familiar with the MRONJ position paper in Japan, and 39% dentists and 9% physicians had encountered MRONJ in their clinical practice. A total of 30% physicians had requested oral health care by a dentist before administering bone-modifying agents (BMA) therapy. The knowledge and experience of MRONJ differed between physicians and dentists. CONCLUSION: The behaviour of physicians and dentists was insufficient to enable medical and dental cooperation for the prevention of MRONJ in patients with osteoporosis. The lack of cooperation between physicians and dentists during osteoporosis treatment in the Shiga prefecture in Japan is documented in this study.

Similarities and differences in metabolites of tongue cancer cells among two- and three-dimensional cultures and xenografts.

Metabolic programming of cancer cells is an essential step in transformation and tumor growth. We established two-dimensional (2D) monolayer and three-dimensional (3D) cultures, the latter called a "tissueoid cell culture system", using four types of tongue cancer cell lines. We also undertook a comprehensive metabolome analysis of three groups that included xenografts created by transplanting the cell lines into nude mice. In addition, we undertook a functional analysis of the mitochondria, which plays a key role in cancer metabolism. Principal component analysis revealed the plots of the four cell lines to be much narrower in 2D culture than in 3D culture and xenograft groups. Moreover, compared to xenografts, the 2D culture had significantly lower levels of most metabolites. These results suggest that the unique characteristics of each cell disappeared in 2D culture, and a type of metabolism unique to monolayer culture took over. Conversely, ATP production, biomass synthesis, and maintenance of redox balance were shown in 3D culture using sufficient nutrients, which closely resembled the metabolic activity in the xenografts. However, there were several differences between the metabolic activity in the 3D culture and xenografts. In vivo, the cancer tissue had blood flow with stromal cells present around the cancer cells. In the xenografts, we detected metabolized and degraded products in the liver and other organs of the host mice. Furthermore, the 3D system did not show impairment of mitochondrial function in the cancer cells, suggesting that cancer cells produce energy simultaneously through mitochondria, as well as aerobic glycolysis.

Factors influencing the long-term hospitalization of bicyclists and motorcyclists with oral and maxillofacial injuries.

BACKGROUND/AIM: Because bicyclists and motorcyclists with oral and maxillofacial injuries often suffer from disabilities requiring long-term treatment, reducing the severity of such injuries is a valuable objective for improving these people's quality of life (QOL). The aims of this study were, first, to present the prevalence and patterns of oral and maxillofacial injuries of bicyclists and motorcyclists and to compare the features of these injuries and, second, to determine the factors contributing to long-term hospitalization for these patients and to propose effective preventive measures. MATERIAL AND METHODS: This was a single-center retrospective analysis. Hospital records from 2011 through 2018 were reviewed for all patients who had sustained oral and maxillofacial injuries in bicycle or motorcycle collisions and had presented at a university hospital which was the only hospital in the region attended 24 hours per day by oral and maxillofacial surgeons. Characteristics of the oral and maxillofacial injuries, injury severity, and factors influencing the length of hospitalization were examined. RESULTS: Records of 130 patients (82 bicyclists and 48 motorcyclists) with a mean age of 28.0 years were analyzed. Thirty-three patients (25.4%) had maxillofacial fractures, with 41 fracture lines while 103 patients (79.2%) had dental injuries and 57 patients (43.8%) had soft-tissue injuries. The distribution and prevalence of oral and maxillofacial injuries were similar for bicyclists and motorcyclists. However, motorcyclists had significantly higher Abbreviated Injury Scale (AIS) scores for facial injuries and the maximum AIS score than did bicyclists. According to a multiple regression analysis, the number of fracture lines and the requirement for intermaxillary fixation were independent factors influencing long-term hospitalization (standard regression coefficients: 6.795 and 6.715, respectively; P < .001). CONCLUSIONS: The number of fracture lines and the use of intermaxillary fixation were independent factors influencing long-term hospitalization of both bicyclists and motorcyclists with oral and maxillofacial injuries.

Maxillofacial Injuries in Cyclists: A Biomechanical Approach for the Analysis of Mechanisms of Mandible Fractures.

PURPOSE: The investigators characterized the occurrence of maxillofacial injuries in cyclists and biomechanically analyzed the mechanisms of mandible fractures. METHODS: We retrospectively analyzed injury data and performed biomechanical analyses with finite element models. Hospital records from 2011 through 2019 were reviewed to identify patients who had sustained oral and maxillofacial injuries while riding a bicycle. Patients with maxillofacial fractures were compared to those without. Logistic regression analysis was performed to identify which variables were independently associated with the occurrence of maxillofacial fractures. To reconstruct the injury scenario (one in which a person falls from a bicycle and contacts the road surface with their face), computer simulations using The Total Human Model for Safety model were performed. RESULTS: The hospital records of 94 patients (62 men, 32 women; 26.1 ± 17.3 years of age) who sustained oral and maxillofacial injuries while riding a bicycle were reviewed. Twenty patients (21.3%) sustained maxillofacial fractures; mandible fractures were most common (16 patients). Patients with maxillofacial fractures were significantly older and had higher severity injuries; however, logistic regression analysis showed that only age was an independent predictor of the occurrence of maxillofacial fracture (odds ratio, 1.03; P = .025). In simulations, higher von Mises stresses were found in the mandible when the cyclist fell with the neck extended and the body horizontal, and consequently, the center of mandibular body strikes the road surface. Contact forces were approximately 8 kN. High tensile stresses occurred laterally and high compressive stresses occurred medially in the mandibular ramus, which indicated that the mandibular ramus deformed in the transverse plane. CONCLUSION: Biomechanical analyses show that mandible fractures can occur when a cyclist falls from a bicycle and their lower face strikes the road's surface.

The Number of Larval Molts Is Controlled by Hox in Caterpillars.

Animals with exoskeletons molt for further growth. In insects, the number of larval (or nymphal) molts varies inter- and intra-specifically, and it is widely accepted that the variation in the number of larval molts is an adaptive response to diverse environmental conditions.1-5 However, the molecular mechanism that underlies the variety and plasticity in the number of larval molts is largely unknown. In the silkworm, Bombyx mori, there are strains that molt three, four, or five times, and these numbers are determined by allelic variation at a single autosomal locus, Moltinism (M).6-9 Here, we demonstrate that the Hox gene Sex combs reduced (Scr) is responsible for the phenotypes of the M locus. Scr is selectively expressed in the larval prothoracic gland (PG), an endocrine organ that produces molting hormones.2Scr represses the biosynthesis of molting hormones in the PG, thereby regulating the incremental increase in body size during each larval instar. Our experiments consistently suggest that the differential expression levels of Scr among the three M alleles result in different growth ratios that ultimately lead to the different number of larval molts. Although the role of Hox genes in conferring segmental identity along the body axis and in molding segment-specific structure later in development has been well established,10-13 the present study identifies an unexpected role of Hox gene in hormone biosynthesis. This new role means that, in addition to shaping segment-specific morphology, Hox genes also drive the evolution of life history traits by regulating animal physiology.

Sensitive Method for the Identification of Potential Sensitizing Impurities in Reaction Mixtures by Fluorescent Nitrobenzoxadiazole-Labeled Glutathione.

Allergic contact dermatitis is a critical issue in the development of new chemicals. Minor impurities with strong skin-sensitizing properties can be generated as byproducts. However, it is very difficult to identify these skin sensitizers in product mixtures. In this study, fluorescent nitrobenzoxadiazole-labeled glutathione (NBD-GSH) was synthesized to identify small amounts of skin sensitizers in reaction mixtures. Twelve known skin sensitizers and three nonsensitizers were reacted with NBD-GSH. Adducts formed only with the skin sensitizers, which allowed for their detection by a fluorescence detector. Liquid chromatography-mass spectrometry (LC-MS) analyses showed that NBD-GSH reacted with the skin sensitizers via its thiol and amino groups. An adduct of NBD-GSH with the strong skin sensitizer 1-chloro-2,4-dinitrobenzene was detected with a limit of detection of 6 × 10-8 mol/L by high-performance liquid chromatography with fluorescence detection. When a reaction mixture from primary alcohol oxidation was incubated with NBD-GSH, a NBD-GSH adduct formed with skin-sensitizing aldehyde impurities and could be specifically detected by LC-MS with fluorescence detection. This method will be useful for detection and identification of small amounts of skin sensitizers in raw materials, intermediates, reaction mixtures, and end products in the chemical industry.

Pulmonary capillary hemangiomatosis-predominant vasculopathy in a patient with rheumatoid arthritis-associated interstitial lung disease: An autopsy report.

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension (PH) associated with poor prognosis. Clinically, it is characterized by severe hypoxemia, centrilobular ground-glass opacities on computed tomography, and pulmonary congestion triggered by pulmonary vasodilating therapy. In some cases, PCH has been reported to develop with other disorders including connective tissue disease; however, to date, no reports have described PCH in a patient with rheumatoid arthritis. We report a case of a 59-year-old male PCH patient with rheumatoid arthritis and associated pulmonary fibrosis. He was initially diagnosed with severe group 3 PH and received sildenafil, which generated a favorable hemodynamic response. However, 5 years later, his pulmonary hemodynamics deteriorated, and he died at the age of 67. An autopsy was performed, and thickening of alveolar septa and capillary proliferation, pathological features of PCH, were extensively observed in both lungs. We discuss when PCH developed, how sildenafil improved his hemodynamics, and how PCH could be clinically detected by noninvasive evaluations.