Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study).

BACKGROUND: Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients. PATIENTS AND METHODS: We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4. RESULTS: Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001). CONCLUSIONS: First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events.

Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients.

BACKGROUND: Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM. PATIENTS AND METHODS: We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies. RESULTS: In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03). CONCLUSIONS: Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

The efficacy of eribulin mesylate for patients with cutaneous angiosarcoma previously treated with taxane: a multicentre prospective observational study.

BACKGROUND: Taxanes are the current first-line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. However, no effective second-line therapy for such patients has been established. METHODS: We designed a single-arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m-2 on days 1 and 8 in a 21-day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression-free survival (PFS) and toxicity assessment. RESULTS: We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference. CONCLUSIONS: ERB showed a promising RR and is a potential candidate for second-line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients. What is already known about this topic? Taxanes are the current first-line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. No effective therapy for taxane-resistant CAS has been established thus far. Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single-arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression-free survival were 8·6 and 3·0 months, respectively. Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively. Although 16 grade 3/4 severe adverse events occurred, all patients recovered. Eribulin showed a promising response rate and is a potential candidate for second-line treatment in CAS after taxane treatment. Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797-798.

2-mm surgical margins are adequate for most basal cell carcinomas in Japanese: a retrospective multicentre study on 1000 basal cell carcinomas.

BACKGROUND: Surgery is the gold standard for basal cell carcinomas (BCC). Current recommended surgical margins for BCCs are determined from studies in Caucasian populations. However, the appropriate surgical margins for BCCs in non-white races are unclear. OBJECTIVES: To investigate the accuracy of preoperative determination of clinical tumour borders and appropriate surgical margins in Japanese patients with BCC. METHODS: The maximum calculated differences in distance between the preoperatively determined surgical margins and the actual histologic tumour side margins were considered as 'accuracy gaps' of clinical tumour borders. Estimated side margin positivity rates (ESMPRs) with narrower (2 and 3 mm) surgical margins were calculated on the basis of the accuracy gaps. RESULTS: Overall, 1000 surgically excised BCCs from 980 Japanese patients were included. The most frequent histologic subtype was nodular BCC (67%). The median accuracy gap was 0.3 mm [interquartile range (IQR): -0.5 to +1 mm]. The ESMPRs with 2- and 3-mm surgical margins were 3.8% and 1.4%, respectively. Only the ESMPRs between the well-defined (n = 921) and poorly defined clinical tumour border groups (n = 79) showed statistical difference [2-mm margin: 3.1% vs. 11.7%, OR: 3.89, 95% confidential interval (CI): 1.41-10.71, P <0.01; 3-mm margin: 0.97% vs. 6.3%, OR: 6.58, 95% CI: 1.67-25.99, P <0.01]. No significant differences in ESMPRs were noted in other subgroups including risk classifications. CONCLUSIONS: The determined clinical tumour border accuracy gaps in this Japanese cohort were negligible. Dermatologic surgeons may use narrower surgical margins with acceptable margin positivity rates. The clarity of clinical tumour borders could be an appropriate guide for selection of different surgical margins in the Japanese cohort.

Epispadias and the associated embryopathies: genetic and developmental basis.

The abnormalities in the urogenital organs are frequently observed as human developmental diseases. Among such diseases, the defects in the upper part of external genitalia are rather rare named epispadias. The cleft in the dorsal part of external genitalia often reaches to the urethra. In general, the urogenital abnormalities accompany defects in the adjacent tissues and organs. The ventral body wall and bladder can also be affected in the patients with dorsal defects of the external genitalia. Therefore, such multiple malformations are often classified as bladder exstrophy and epispadias complex (BEEC). Because of the lower frequency of such birth defects and their early embryonic development, animal models are required to analyze the pathogenic mechanisms and the functions of responsible genes. Mutant mouse analyses on various signal cascades for external genitalia and body wall development are increasingly performed. The genetic interactions between growth factors such as bone morphogenetic proteins (Bmp) and transcription factors such as Msx1/2 and Isl1 have been suggested to play roles for such organogenesis. The significance of epithelial-mesenchymal interaction (EMI) is suggested during development. In this review, we describe on such local interactions and developmental regulators. We also introduce some mutant mouse models displaying external genitalia-body wall abnormalities.

5α-Dihydrotestosterone negatively regulates cell proliferation of the periurethral ventral mesenchyme during urethral tube formation in the murine male genital tubercle.

Androgen is an essential factor involved in masculinization of external genitalia. Failure of the exposure to 5α-dihydrotestosterone (DHT) causes a hypoplastic penile size and urethral abnormality. The main pathology of hypospadias is defective urethral closure on the ventral side of the penis. Hormone-dependent genes are suggested as the causative factors. However, the detailed mechanisms of DHT functions on urethral tube formation remain unknown. Androgen is both a positive and negative regulator of cell proliferation. The roles of locally converted DHT in cell proliferation at the periurethral mesenchyme have not been elucidated. We revealed the expression pattern of 5α-reductase type 2 mRNA (Srd5a2) and local DHT distribution by direct measurement in this study. We also analyzed periurethral mesenchymal cell proliferation status using systematic three-dimensional (3D) reconstruction analyses. A prominent Srd5a2 expression and localized DHT distribution on the ventral side of the genital tubercle were detected. Cell proliferation was reduced in this mesenchymal region during urethral formation. The current results suggest the presence of the possible negative regulation of cell proliferation by DHT. Moreover, cell proliferation related to urethral tube formation was revealed to be DHT dose dependent. These data are expected to contribute to the understanding of the mode of regulation of cell proliferation related to urethral tube formation by DHT. These findings may also offer insight into the understanding of human hypospadias and related hormone-dependent factors.

Identification and functional activity of a staphylocoagulase type XI variant originating from staphylococcal food poisoning isolates.

UNLABELLED: Staphylocoagulase, an extracellular protein secreted by Staphylococcus aureus, has been used as an epidemiological marker. At least 12 serotypes and 24 genotypes subdivided on the basis of nucleotide sequence have been reported to date. In this study, we identified a novel staphylocoagulase nucleotide sequence, coa310, from staphylococcal food poisoning isolates that had the ability to coagulate plasma, but could not be typed using the conventional method. The protein encoded by coa310 contained the six fundamental conserved domains of staphylocoagulase. The full-length nucleotide sequence of coa310 shared the highest similarity (77·5%) with that of staphylocoagulase-type (SCT) XIa. The sequence of the D1 region, which would be responsible for the determination of SCT, shared the highest similarity (91·8%) with that of SCT XIa. These results suggest that coa310 is a novel variant of SCT XI. Moreover, we demonstrated that coa310 encodes a functioning coagulase, by confirming the coagulating activity of the recombinant protein expressed from coa310. This is the first study to directly demonstrate that Coa310, a putative SCT XI, has coagulating activity. These findings may be useful for the improvement of the staphylocoagulase-typing method, including serotyping and genotyping. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to identify a novel variant of staphylocoagulase type XI based on its nucleotide sequence and to demonstrate coagulating activity in the variant using a recombinant protein. Elucidation of the variety of staphylocoagulases will provide suggestions for further improvement of the staphylocoagulase-typing method and contribute to our understanding of the epidemiologic characterization of Staphylococcus aureus.

Peripheral circulation evaluation with near-infrared spectroscopy in skeletal muscle during cardiopulmonary bypass.

BACKGROUND: We designed a non-invasive, observational, real-time study, using near-infrared spectroscopy (NIRS) to assess the in vivo effects of cardiopulmonary bypass (CPB) on patients' skeletal muscle as well as the effects of hemodilution and hypothermia on tissue oxygen delivery during CPB. METHODS: The study included 20 consecutive adult patients undergoing open-heart surgery with CPB. Evaluation parameters for peripheral circulation were measured using the NIRO-200NX and recorded every 30 seconds. To assess how hemodilution influences peripheral circulation parameters, we compared data between a group of patients with hematocrit (Hct) values >22% (high Hct group) and those with Hct values ⩽22% (low Hct group). RESULTS: Changes in the concentration of oxygenated hemoglobin (ΔO2Hb, µmol/L), which flows into the skeletal muscle, was an important factor for deciding the tissue oxygenation index (TOI%), showing the tissue oxygen saturation. The low Hct group showed a significant increase in the normalized tissue hemoglobin index (nTHI), showing the percentage change in the amount of initial hemoglobin and TOI compared to the high Hct group. Changes in the concentration of oxygenated hemoglobin (ΔO2Hb, µmol/L) and deoxygenated hemoglobin (ΔHHb, µmol/L) were significantly less in the low Hct group than in the high Hct group, thus, showing good peripheral circulation despite the low hematocrit levels. CONCLUSION: Our study indicated the presence of a compensatory mechanism in which increased blood flow of the microcirculation is in compensation for the lack of oxyhemoglobin delivery caused by hemodilution.

Receptor-type protein tyrosine phosphatase κ directly dephosphorylates CD133 and regulates downstream AKT activation.

Although CD133 has been considered to be a molecular marker for cancer stem cells, its functional roles in tumorigenesis remain unclear. We here examined the molecular basis behind CD133-mediated signaling. Knockdown of CD133 resulted in the retardation of xenograft tumor growth of colon cancer-derived HT-29 and LoVo cells accompanied by hypophosphorylation of AKT, which diminished ß-catenin/T-cell factor-mediated CD44 expression. As tyrosine residues of CD133 at positions 828 and 852 were phosphorylated in HT-29 and SW480 cells, we further addressed the significance of this phosphorylation in the tumorigenesis of SW480 cells expressing mutant CD133, with substitution of these tyrosine residues by glutamate (CD133-EE) or phenylalanine (CD133-FF). Forced expression of CD133-EE promoted much more aggressive xenograft tumor growth relative to wild-type CD133-expressing cells accompanied by hyperphosphorylation of AKT; however, CD133-FF expression had negligible effects on AKT phosphorylation and xenograft tumor formation. Intriguingly, the tyrosine phosphorylation status of CD133 was closely linked to the growth of SW480-derived spheroids. Using yeast two-hybrid screening, we finally identified receptor-type protein tyrosine phosphatase κ (PTPRK) as a binding partner of CD133. In vitro studies demonstrated that PTPRK associates with the carboxyl-terminal region of CD133 through its intracellular phosphatase domains and also catalyzes dephosphorylation of CD133 at tyrosine-828/tyrosine-852. Silencing of PTPRK elevated the tyrosine phosphorylation of CD133, whereas forced expression of PTPRK reduced its phosphorylation level markedly and abrogated CD133-mediated AKT phosphorylation. Endogenous CD133 expression was also closely associated with higher AKT phosphorylation in primary colon cancer cells, and ectopic expression of CD133 enhanced AKT phosphorylation. Furthermore, lower PTPRK expression significantly correlated with the poor prognosis of colon cancer patients with high expression of CD133. Thus, our present findings strongly indicate that the tyrosine phosphorylation of CD133, which is dephosphorylated by PTPRK, regulates AKT signaling and has a critical role in colon cancer progression.

Disruption of the temporally regulated cloaca endodermal ß-catenin signaling causes anorectal malformations.

The cloaca is temporally formed and eventually divided by the urorectal septum (URS) during urogenital and anorectal organ development. Although congenital malformations, such as anorectal malformations (ARMs), are frequently observed during this process, the underlying pathogenic mechanisms remain unclear. ß-Catenin is a critical component of canonical Wnt signaling and is essential for the regulation of cell differentiation and morphogenesis during embryogenesis. The expression of ß-catenin is observed in endodermal epithelia, including URS epithelia. We modulated the ß-catenin gene conditionally in endodermal epithelia by utilizing tamoxifen-inducible Cre driver line (Shh(CreERT2)). Both ß-catenin loss- and gain-of-function (LOF and GOF) mutants displayed abnormal clefts in the perineal region and hypoplastic elongation of the URS. The mutants also displayed reduced cell proliferation in the URS mesenchyme. In addition, the ß-catenin GOF mutants displayed reduced apoptosis and subsequently increased apoptosis in the URS epithelium. This instability possibly resulted in reduced expression levels of differentiation markers, such as keratin 1 and filaggrin, in the perineal epithelia. The expression of bone morphogenetic protein (Bmp) genes, such as Bmp4 and Bmp7, was also ectopically induced in the epithelia of the URS in the ß-catenin GOF mutants. The expression of the Msx2 gene and phosphorylated-Smad1/5/8, possible readouts of Bmp signaling, was also increased in the mutants. Moreover, we introduced an additional mutation for a Bmp receptor gene: BmprIA. The Shh(CreERT2/+); ß-catenin(flox(ex3)/+); BmprIA(flox/-) mutants displayed partial restoration of URS elongation compared with the ß-catenin GOF mutants. These results indicate that some ARM phenotypes in the ß-catenin GOF mutants were caused by abnormal Bmp signaling. The current analysis revealed the close relation of endodermal ß-catenin signaling to the ARM phenotypes. These results are considered to shed light on the pathogenic mechanisms of human ARMs.

Algorithm for selecting appropriate transfer support equipment and a robot based on user physical ability.

In this present paper, we propose an algorithm for selecting appropriate transfer support equipment and robot based on the physical ability of the user. In addition, we describe the relationship between physical human features and the burden during standing when using a standing support robot. Although a number of care support devices have been developed, assistive robots are not yet popular because users do not know which devices are appropriate for their needs or physical abilities. In this study, we focus on a transfer support device and propose an algorithm for selecting transfer support equipment and a robot that suits the user's physical ability. We investigated the relationship between standing support equipment including a robot and the physical burden during standing, which is a basic transfer motion. Experimentally, we analyzed and calculated the knee and ankle joint moments and discussed the relationship between standing support equipment and knee and ankle joint moments during standing; we also investigated and the relationship between physical human features and the knee joint moment during standing. Our results identified standing support equipment that was appropriate to the user's physical ability. We found that it was effective to provide an up/down seat to persons having low residual ability; a standing support robot is appropriate for people having less residual ability in the knees, and a railing is suitable for people having low residual ability in the ankles.

The etiologic role of human papillomavirus in penile cancers: a study in Vietnam.

BACKGROUND: We investigated the aetiologic role of human papillomavirus (HPV) in 120 penile squamous cell carcinomas (PSCCs) from Vietnam. METHODS: Human papillomavirus DNA was detected by PCR using SPF10 primers and a primer set targeting HPV-16 E6. The INNO-LiPA HPV genotyping kit was used to determine genotype. Human papillomavirus-16 viral load and physical status were determined by real-time PCR. P16(INK4A) protein expression was investigated by immunohistochemistry. RESULTS: Human papillomavirus DNA was detected in 27 of 120 (23%) PSCCs. The most frequently detected genotype was HPV-16 (24 of 27 cases, 89%). In 16 of 18 (89%) HPV-16-positive cases, the HPV DNA was considered to be integrated into the host genome. The geometric mean of the HPV-16 viral load was 0.4 copies per cell. P16(INK4A) overexpression was significantly related to PSCCs infected with high-risk HPV (P=0.018) and HPV-16 copy numbers (P<0.001). CONCLUSION: Human papillomavirus-16 DNA integration and p16(INK4A) overexpression in high-risk HPV detected PSCCs suggested an aetiologic role of high-risk HPV in the development of PSCCs.

Thin-section CT findings of patients with acute Streptococcus pneumoniae pneumonia with and without concurrent infection.

OBJECTIVES: The aim of this study was to compare the pulmonary thin-section CT findings of patients with acute Streptococcus pneumoniae pneumonia with and without concurrent infection. METHODS: The study group comprised 86 patients with acute S. pneumoniae pneumonia, 36 patients with S. pneumoniae pneumonia combined with Haemophilus influenzae infection, 26 patients with S. pneumoniae pneumonia combined with Pseudomonas aeruginosa infection and 22 patients with S. pneumoniae pneumonia combined with methicillin-susceptible Staphylococcus aureus (MSSA) infection. We compared the thin-section CT findings among the groups. RESULTS: Centrilobular nodules and bronchial wall thickening were significantly more frequent in patients with pneumonia caused by concurrent infection (H. influenzae: p<0.001 and p<0.001, P. aeruginosa: p<0.001 and p<0.001, MSSA: p<0.001 and p<0.001, respectively) than in those infected with S. pneumoniae alone. Cavity and bilateral pleural effusions were significantly more frequent in cases of S. pneumoniae pneumonia with concurrent P. aeruginosa infection than in cases of S. pneumoniae pneumonia alone (p<0.001 and p<0.001, respectively) or with concurrent H. influenzae (p<0.05 and p<0.001, respectively) or MSSA infection (p<0.05 and p<0.05, respectively). CONCLUSIONS: When a patient with S. pneumoniae pneumonia has centrilobular nodules, bronchial wall thickening, cavity or bilateral pleural effusions on CT images, concurrent infection should be considered.

Granulocyte and monocyte adsorption apheresis as an effective treatment for Reiter disease.

Reiter disease (RD) is characterized by a triad of sterile arthritis, urethritis and conjunctivitis. The conditions occur concomitantly or sequentially, and are associated with mucocutaneous features such as circinate balanitis and stomatitis. Arthritis usually occurs in attacks followed by recovery, but it sometimes progresses to permanent damage of the affected joints. Because the symptoms of this disorder are attributable to activated neutrophils, we assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) in a 73-year-old man with RD who had skin rashes on his penis, scrotum and right hand, with severe arthralgia. The patient's skin rash and joint pain responded dramatically to five sessions of GCAP delivered at intervals of 5 days. We present a detailed description of the patient and discuss the mechanisms of GCAP, and suggest that GCAP may be useful for treating RD.

Preparation of biologically active single-chain variable antibody fragments that target the HIV-1 gp120 V3 loop.

KD-247 is a humanized monoclonal antibody that targets the third hypervariable (V3) loop of gp120. It can efficiently neutralize a broad panel of clade B, but not non-clade B, HIV-1 isolates. To overcome this limitation, we are seeking to prepare genetically-engineered single-chain variable fragments (scFvs) of KD-247 that will have broader neutralizing activity against both clade B and non-clade B HIV-1 isolates. Initial attempts of optimizing the expression of KD-247 scFv have resulted in the formation of insoluble protein. Therefore, we have established purification protocols to recover, purify, and refold the KD-247 scFv from inclusion bodies. The protocol involved step-wise refolding of denatured scFv by dilution, dialysis, and on-column nickel-affinity purification. Monomeric scFv was further purified by size-exclusion chromatography. Using far UV circular dichroism (CD) spectroscopy we confirmed the expected beta-sheet profile of the refolded KD-247 scFv. Importantly, the refolded KD-247 scFv showed neutralizing activity against replication-competent HIV-1 BaL and JR-FL Env pseudotyped HIV-1, at potency comparable to that of the native full-size KD-247 antibody. Ongoing studies focus on the application of this system in generating KD-247 scFv variants with the ability to neutralize clade B and non-clade B HIV-1 isolates.

Radiological findings in acute Haemophilus influenzae pulmonary infection.

OBJECTIVE: The aim of this study was to assess pulmonary thin-section CT findings in patients with acute Haemophilus influenzae pulmonary infection. METHODS: Thin-section CT scans obtained between January 2004 and March 2009 from 434 patients with acute H. influenzae pulmonary infection were retrospectively evaluated. Patients with concurrent infection diseases, including Streptococcus pneumoniae (n=76), Staphylococcus aureus (n=58) or multiple pathogens (n=89) were excluded from this study. Thus, our study group comprised 211 patients (106 men, 105 women; age range, 16-91 years, mean, 63.9 years). Underlying diseases included cardiac disease (n=35), pulmonary emphysema (n=23), post-operative status for malignancy (n=20) and bronchial asthma (n=15). Frequencies of CT patterns and disease distribution of parenchymal abnormalities, lymph node enlargement and pleural effusion were assessed by thin-section CT. RESULTS: The CT findings in patients with H. influenzae pulmonary infection consisted mainly of ground-glass opacity (n=185), bronchial wall thickening (n=181), centrilobular nodules (n=137) and consolidation (n=112). These abnormalities were predominantly seen in the peripheral lung parenchyma (n=108). Pleural effusion was found in 22 patients. Two patients had mediastinal lymph node enlargement. CONCLUSION: These findings in elderly patients with smoking habits or cardiac disease may be characteristic CT findings of H. influenzae pulmonary infection.