TIM-3 expression induces resistance to PD-1 inhibitor in G-CSF-producing lung spindle cell carcinoma: A case report.

Lung spindle cell carcinoma is an aggressive subtype of pleomorphic lung cancer resistant to cytotoxic chemotherapy. Programmed cell death-1 (PD-1) inhibitors have been reported to have clinical effects in patients with spindle cell carcinoma; however, the resistance mechanism to PD-1 inhibitors is yet to be fully elucidated. Herein, we report the case of an 88-year-old man with G-CSF-producing spindle cell carcinoma who acquired resistance to PD-1/PD-ligand 1 (L1) inhibitor in an early setting after a remarkable response. A histopathological review of the resistant specimen revealed a low count of CD8+ T cells and a predominant presence of M2 and TIM-3+ macrophages, indicating the presence of an immunosuppressive microenvironment. Our findings suggest a novel resistance mechanism to PD-1/PD-L1 inhibitors in G-CSF-producing spindle cell carcinoma.

Phase II study of IRInotecan treatment after COmbined chemo-immunotherapy for extensive-stage small cell lung cancer: Protocol of IRICO study.

INTRODUCTION: Combined treatment using anti-programmed death-ligand 1 antibody (anti-PD-L1) and platinum-etoposide is the current standard first-line treatment for patients with extensive-stage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ES-SCLC after the first-line treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ES-SCLC, and treatment with irinotecan is well established as both a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the second- or later-line setting for patients with ES-SCLC who have been previously treated with combined treatment. METHODS: Our study will enroll total 30 patients who are diagnosed with ES-SCLC and have experienced disease progression after the combined treatment. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4 weeks. Doses of irinotecan (100/80/60 mg/m2 ) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator's decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progression-free survival, and safety. DISCUSSION: Since the present first-line treatment has been changed to the combined treatment, the second- or later-line treatment should be re-evaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This study demonstrates and re-evaluates the clinical benefits of irinotecan after combined treatment with anti-PD-L1 and platinum-etoposide for patients with ES-SCLC. REGISTRATION DETAILS: This study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021.

Pneumoconiosis with a Sarcoid-Like Reaction Other than Beryllium Exposure: A Case Report and Literature Review.

Background: Chronic beryllium disease (CBD) is a granulomatous disease that resembles sarcoidosis but is caused by beryllium. Clinical manifestations similar to those observed in CBD have occasionally been reported in exposure to dusts of other metals. However, reports describing the clinical, radiographic, and pathological findings in conditions other than beryllium-induced granulomatous lung diseases, and detailed information on mineralogical analyses of metal dusts, are limited. Case presentation: A 51-year-old Japanese man with rapidly progressing nodular shadows on chest radiography, and a 10-year occupation history of underground construction without beryllium exposure, was referred to our hospital. High-resolution computed tomography showed well-defined multiple centrilobular and perilobular nodules, and thickening of the intralobular septa in the middle and lower zones of both lungs. No extrathoracic manifestations were observed. Pathologically, the lung specimens showed 5-12 mm nodules with dust deposition and several non-necrotizing granulomas along the lymphatic routes. X-ray analytical electron microscopy of the same specimens revealed aluminum, iron, titanium, and silica deposition in the lung tissues. The patient stopped smoking and changed his occupation to avoid further dust exposure; the chest radiography shadows decreased 5 years later. Conclusion: The radiological appearances of CBD and sarcoidosis are similar, although mediastinal or hilar lymphadenopathy is less common in CBD and is usually seen in the presence of parenchymal opacities. Extrathoracic manifestations are also rare. Despite limited evidence, these findings are similar to those observed in pneumoconiosis with a sarcoid-like reaction due to exposure to dust other than of beryllium. Aluminum is frequently detected in patients with pneumoconiosis with a sarcoid-like reaction and is listed as an inorganic agent in the etiology of sarcoidosis. It was also detected in our patient and may have contributed to the etiology. Additionally, our case suggests that cessation of dust exposure may contribute to improvement under the aforementioned conditions.

Five-year longitudinal study of dental caries risk associated with Streptococcus mutans and Streptococcus sobrinus in individuals with intellectual disabilities.

Streptococcus mutans (S. mutans) and Streptococcus sobrinus (S. sobrinus) are important etiologic agents in human dental caries. Using quantitative real-time polymerase chain reaction assays for the presence of those strains, we examined 145 outpatients with intellectual disability (ID), calculated the proportion of each of these strains to total bacteria, and compared dental caries incidence over 5 years. Plaque samples were collected from all erupted tooth sites, and dental examinations were performed annually to determine numbers of decayed, missing, and filled teeth (DMFT score; World Health Organization caries diagnostic criteria). Elevated DMFT scores were calculated as ∆DMFT, and sites of newly affected caries (∆SNAC) were identified. Sixty-six patients had both strains. The proportion of S. mutans to total bacteria was moderately correlated with DMFT in year 2, ∆DMFT in years 2 and 5, and ∆SNAC in years 2 and 5 (correlation coefficient = 0.470, P < 0.001), while the proportion of S. sobrinus to total bacteria was moderately correlated with DMFT in years 2 and 5, ∆DMFT in years 1, 2, and 5, and ∆SNAC in years 2 and 5 (correlation coefficient = 0.695, P < 0.001). Individuals with ID who harbored both bacterial strains had a higher risk of dental caries and a significantly higher proportion of S. sobrinus to total bacteria.

Longitudinal study of dental caries incidence associated with Streptococcus mutans and Streptococcus sobrinus in patients with intellectual disabilities.

BACKGROUND: Mutans streptococci (Streptococcus mutans and S. sobrinus) are considered to be major etiologic agents of dental caries. Using a polymerase chain reaction method, we detected those bacteria from 145 outpatients (6-30 years old) with intellectual disabilities (ID) and their presence was compared with the incidence of dental caries. METHODS: Plaque samples were collected from all erupted tooth sites in subjects with a sterile toothbrush. A dental examination was performed to determine the number of decayed and filled teeth (DFT score) in permanent dentition using the WHO caries diagnostic criteria. A Mann-Whitney U-test was employed to compare the caries scores between combinations of the bacteria, and with a Wilcoxon rank test used to compare caries scores between the baseline and after 1 year. RESULTS: Among all subjects, S. mutans and S. sobrinus were possessed by 78.7 and 83.5%, respectively, while 13.1% were positive for S. mutans alone, 17.9% for S. sobrinus alone, and 65.6% for both organisms, with 3.4% were negative for both. The mean DFT score of subjects positive for both S. mutans and S. sobrinus at after 1 year was significantly higher than that of those positive for S. mutans alone (P < 0.01). The increase in caries increment was also significantly greater in subjects with both bacteria detected (P < 0.001). CONCLUSION: Our results indicate that patients with ID harboring both S. mutans and S. sobrinus have a significantly higher incidence of dental caries than those with S. mutans alone.

Sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells in mice.

We evaluated the sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells. Adult C57BL/6 mice were daily exposed to 0, 2, 10, 50, and 250 mGy γ-ray for 1 month in succession, respectively. The damage of hematopoietic stem/progenitor cells in bone marrow were investigated within 2 hours (acute phase) or at 3 months (chronic phase) after the last exposure. Daily exposure to over 10 mGy γ-ray significantly decreased the number and colony-forming capacity of hematopoietic stem/progenitor cells at acute phase, and did not completely recover at chronic phase with 250 mGy exposure. Interestingly, the daily exposure to 10 or 50 mGy γ-ray decreased the formation of mixed types of colonies at chronic phase, but the total number of colonies was comparable to control. Immunostaining analysis showed that the formation of 53BP1 foci in c-kit(+) stem/progenitor cells was significantly increased with daily exposure to 50 and 250 mGy at acute phase, and 250 mGy at chronic phase. Many genes involved in toxicity responses were up- or down-regulated with the exposures to all doses. Our data have clearly shown the sensitivity and dose dependency of radiation-induced injury in hematopoietic stem/progenitor cells of mice with daily exposures to 2 ~ 250 mGy γ-ray.

Prevalence of Porphyromonas gingivalis fimA genotypes in Japanese children.

Porphyromonas gingivalis FimA fimbriae have been classified into 6 genotypes (types I-V and Ib) based on the diversity of the fimA genes encoding the fimbrial subunits. We investigated the prevalence of fimA genotype in Japanese children. Dental plaque specimens were obtained from 400 subjects (age; 2 to 15 years), including 134 with healthy gingiva, 239 with gingivitis and 27 with periodontitis, and then analyzed by polymerase chain reaction. P. gingivalis was detected in 1.5%, 10.0% and 29.6% of these subjects, respectively. Significant differences were observed with regard to P. gingivalis infection among the groups [chi-squared analysis: gingivitis vs. healthy, P < 0.01, odds ratio (OR) = 7.4; periodontitis vs. healthy, P < 0.001, OR = 27.8]. In P. gingivalis-positive subjects with periodontitis, the most prevalent fimA types were type Ib/type II combination (37.5%) and type IV (37.5%), followed by type II (25.0%), while type IV (33.3%) and type II (29.2%) were most often detected in those with gingivitis. Our results suggest that the presence of P. gingivalis is associated with periodontal diseases, and that the type II, IV and Ib/II combination are the most common among fimA genotypes.

Late Established Mutans Streptococci in Children over 3 Years Old.

Acquisition of mutans streptococci has been reported to most commonly occur at approximately 26 months of age. In the present study, we detected Streptococcus mutans and S. sobrinus using polymerase chain reaction (PCR) assays in children, then re-examined the subjects to determine the time of acquisition of these bacteria over a 1-year period. The subjects were 57 children ranging in age from 3 to 5 years old, each with primary dentition. Plaque samples were collected from all erupted tooth sites using a sterile toothbrush. PCR assays were performed to detect the targeted mutans streptococci at the beginning of the study (baseline) and after 1 year. At the baseline examination, the prevalence of S. mutans and S. sobrinus was 61.4% and 54.4%, respectively, in all subjects, of whom 14 (24.6%) were positive for S. mutans alone, 10 (17.5%) for S. sobrinus alone, and 21 (36.8%) for both S. mutans and S. sobrinus, with 12 (21.1%) negative for both. After 1 year, 4 of 22 (18.2%) subjects newly had acquired S. mutans and 15 of 26 (57.7%) had aquired S. sobrinus, while 5 (8.8%) remained negative for both bacteria. The age of the first positive S. mutans finding ranged from 49 to 71 months, while that for S. sobrinus ranged from 49 to 81 months old. Our results suggest that S. sobrinus becomes established later than S. mutans in the oral cavities of children over the age of 3 years old.

Subgingival distribution of Campylobacter rectus and Tannerella forsythensis in healthy children with primary dentition.

OBJECTIVE: It is important to know how many subgingival plaque samples should be assayed from a child to ascertain infection with a periodontal pathogen. Plaque samples from several sites may fail to detect some important bacteria if only a limited number of gingival sites are sampled. The purpose of this study was to evaluate the detection of periodontal pathogens in a large number of subgingival sites in the same children in order to determine the number of samples necessary. METHODS: Ten children, aged 4-6 years, with complete primary dentition were enrolled in this study. Plaque samples from the mesio-buccal aspect of each erupted tooth were first collected by gently inserting a sterile paper point for 10s. Purified genomic DNA from all plaque samples was prepared for polymerase chain reaction. The primers for species-specific 16S ribosomal RNA sequence were selected as the target sequence. Standard strains of Campylobacter rectus and Tannerella forsythensis (formerly Bacteroides forsythus) were used as control strains. RESULTS: All subjects were found positive for C. rectus and T. forsythensis with the mean of positive sites at 17.6 +/- 2.4 (range: 12-20 sites) for C. rectus and 9.3 +/- 5.0 (range: 1-19) for T. forsythensis. The mean number of positive sites was 1.7 +/- 0.8 for C. rectus and 6.5 +/- 4.9 for T. forsythensis, with a confidence ratio of 95%. CONCLUSIONS: We concluded that two or more random sites for C. rectus and seven or more random sites for T. forsythensis from children to detect those bacteria at 95% probability.

Longitudinal study of dental caries incidence associated with Streptococcus mutans and Streptococcus sobrinus in pre-school children.

Streptococcus mutans and Streptococcus sobrinus are known to be associated with the development of dental caries. In this study these bacteria were detected in pre-school children (each with primary dentition, age range 3-5 years, n = 60) using a PCR method, and then their presence was compared with the incidence of dental caries over a 1-year period. Plaque samples were collected from all erupted tooth sites using a sterile toothbrush. Dental examinations at the beginning of the study (baseline) and after 1 year were also performed to determine decayed, missing, filled teeth (dmft) scores using WHO caries diagnostic criteria. The prevalences of S. mutans and S. sobrinus across all the subjects were 61.7% and 56.6%, respectively; 13 subjects (21.7%) were positive for S. mutans alone, 10 (16.6%) were positive for S. sobrinus alone and 24 (40.0%) were positive for both S. mutans and S. sobrinus, whereas 13 (21.7%) were negative for both S. mutans and S. sobrinus. dmft scores of subjects positive for both S. mutans and S. sobrinus at baseline and after 1 year were significantly higher than of those positive for S. mutans alone at the same stages (P < 0.01 and P < 0.001, respectively). The caries incremental increase was also significantly greater in those with both bacteria detected (P < 0.05). Our results indicate that pre-school children harbouring both S. mutans and S. sobrinus have a significantly higher incidence of dental caries than those with S. mutans alone.

[Emergency microlaryngosurgery for a huge post-intubation laryngeal granuloma].

A 55-year-old woman who had undergone esophagectomy 3 months earlier developed a huge post-intubation laryngeal granuloma. She was scheduled for emergency microlaryngosurgery. Anesthesia was induced with 8% sevoflurane in oxygen under spontaneous respiration. After confirming no airway compromise, the spontaneous respiration was obtunded by forced manual ventilation without using a muscle relaxant. The trachea was intubated easily with an endotracheal tube. Anesthesia was maintained with sevoflurane and nitrous oxide supplemented with intravenous fentanyl. The granuloma removed was 11 x 8 mm in diameter. There were no respiratory complications during and after anesthesia and surgery.

Intra-familial distribution of nine putative periodontopathogens in dental plaque samples analyzed by PCR.

It is of great importance to understand the distribution of periodontopathogens within family members when considering the risk of periodontitis in children. The purpose of this study was to investigate the distribution of periodontopathogens among family members. We used the polymerase chain reaction method to test 4,8, and 7 probands with healthy gingiva, gingivitis, and periodontitis, respectively, and their 60 immediate family members. Plaque samples were collected from all erupted teeth sites using a sterile toothbrush. In 161 of the 165 positive cases, if a child harbored one of the periodontopathogens then at least one of the parents was also positive for the same bacterium. The prevalence of parent-child co-infection was 42.9% for Actinobacillus actinomycetemcomitans, 21.4% for Porphyromonas gingivalis, 29.2% for Treponema denticola, 59.5% for Tannerella forsythensis (Bacteroides forsythus) and 16.7% for Prevotella intermedia. Our results indicate that parents could be an important source of periodontopathogens for the colonization that occurs in their children.

PCR detection of Streptococcus mutans and S. sobrinus in dental plaque samples from Japanese pre-school children.

Streptococcus mutans and S. sobrinus are associated with the development of dental caries. These bacteria were detected by PCR and then their presence was compared with the incidence of dental caries in 77 Japanese pre-school children. Plaque samples were collected from all erupted tooth sites in the subjects, aged 3-5 years old and each with primary dentition, with a sterile toothbrush. A dental examination was performed for dmft (decayed, missing, filled, total) with the WHO caries diagnostic criteria. In all subjects, the prevalence of S. mutans and S. sobrinus was 72.8% and 61.1%, respectively; 19 (24.7%) were positive for S. mutans alone, 10 (13.0%) were positive for S. sobrinus alone, 37 (48.1%) were positive for both S. mutans and S. sobrinus, and 11 (14.3%) were negative for both S. mutans and S. sobrinus. The dmft scores of children positive for both S. mutans and S. sobrinus were significantly higher than those positive for S. mutans alone. These results indicate that children harbouring both S. mutans and S. sobrinus have a significantly higher incidence of dental caries than those with S. mutans alone.

Comparaçäo entre esquemas antibióticos com Imipenem/Cilastatina e Cefalosporinas de 3o. geraçäo no tratamento de pneumonias em pacientes com fatores de risco / Comparison between Imipenem/Cilastatin and third generation Cephalosporins in the treatment of pneumonia in patients with risk factors

Trinta e cinco episódios de pneumonia em 33 pacientes foram tratados com dois esquemas antibióticos: no grupo A foi utilizado Imipenem e no B uma cefalosporina de 3ª geraçäo; de acordo com dados bacteriológicos e/ou clínicos foram acrescentados outros antibióticos (vancomicina e aminoglicosídeo, principalmente). Todos os pacientes apresentavam fator de risco (em 16 vezes, mais de um fator) e a pneumonia foi adquirida no hospsital 20 vezes. Bactérias foram isoladas em 27 episódios: por aspirado transtraqueal em 18, hemocultura em dois, líquido pleural e um e escarro selecionado em seis. Ocorreram oito óbitos, dos quais seis no grupo B e dois no grupo A; excluindo-se os episódios por S. aureus, a mortalidade foi quatro e zero, respectivamente (p = 0,06 - teste de Fisher). A comparaçäo entre os óbitos e os que evoluíram favoravelmente mostra que as condiçöes de base tiveram provavelmente maior influência que o esquema antibiótico usado. Para conclusöes definitivas sobre a superioridade de um esquema sobre o outro é necessário aumentar a amostra, entretanto, é provável que o impemen, por seu espectro mais amplo, seja superior

Infeccçöes pulmonares em adultos: dois esquemas posológicos com ofloxacina / Pulmonary infections in adults: two therapeutics regimens of ofloxacin

Foram estudados 37 pacientes portadores de infecção bacteriana do trato respiratório inferior, dos quais 19 apresentavam broncopneumopatia prévia. Os pacientes foram tratados com ofloxacina, uma nova quinoloma, por 10 dias, com ingestão de um comprimido (200 mg) duas vezes ao dia (Grupo I) ou 2 comprimidos (400mg) duas vezes ao dia (Grupo II). O estudo foi aberto, randomizado. No grupo I, 10 pacientes eram portadores de bronquite aguda, três apresentavam exacerbação de bronquite crônica, quatro bronquiectasia infectada e dois pneumonia. No Grupo II havia, respectivamente, cinco, sete, cinco e um pacientes. Em dois pacientes a droga foi suspensa por intolerância, principalmente gástrica, sendo um não analisado nos resultados. Trinta e três pacientes curaram ou melhoraram (91,8 por cento), sendo a avaliação essencialmente clínica, pois somente em 10 pacientes a cultura de escarro selecionado foi positiva. Culturas após o final do tratamento revelaram persistência do germe em apenas um paciente (S. aureus), com preservação da sensibilidade. Não houve diferença significativa nas taxas de cura/melhora nos Grupos I e II. Em conclusão: como a ofloxacina tem eficácia semelhante aos antibióticos clássicos usados em infecção bacteriana do trato respiratório inferior e como a incidência de efeitos colaterais é baixa, o agente pode ser incluído entre os antibióticos indicados neste tipo de infecção.

Tratamento de infecçöes brônquicas bacterianas agudas com a associaçäo trimetoprima-sulfadiazina (cotrimazina): resultados em 20 pacientes ambulatoriais / Treatment of acute bacterial bronchial infections with trimethoprim-sulphadiazine association (cotrimazine): results in 20 patients

Vinte pacientes portadores de infecçäo brônquica bacteriana foram tratados com a associaçäo Trimetoprima-Sulfadiazina (cotrimazina) (90 mg e 410 mg respectivamente por comprimido) - 1 comprimido a cada 12 horas por 10 dias. A média de idade dos pacientes foi 45,2 + ou - 20,4 anos e a média de duraçäo dos sintomas 10,7 + ou - 8,07 dias. Onze pacientes apresentavam patologia brônquica e/ou pulmonar pré-existente. Foram obtidas 33 culturas de escarro no pré e no pós-tratamento, das quais 30 foram consideradas adequadas pela citologia concomitante. Quinze pacientes foram considerados clinicamente curados (desaparecimento da expectoraçäo), 3 melhorados (permanência da expectoraçäo, mas com reduçäo da quantidade) e 2 como falha. A avaliaçäo bacteriológica foi dificultada por limitaçöes do próprio método. Seis pacientes apresentaram novos sintomas após o início do tratamento, tendo havido 2 abandonos por intolerância; contudo, muitos destes sintomas näo podem ser imputados diretamente ao medicamento. Os níveis de transaminases, uréia, hemoglobina e leucócitos no sangue periférico näo se alteraram com o tratamento

Infecçäo hospitalar: reduçäo do consumo de antibióticos devida à açäo da Comissäo de Controle de Infecçäo Hospitalar no Hospital do Servidor Público Municipal de Säo Paulo / Hospital infection: reduction of antibiotics consumption due to the action of the Hospital Infection Control Committee in the Hospital do Servidor Público Municipal de Säo Paulo

Estudou-se a incidência de infecçöes hospitalares e o consumo de antibióticos no Hospital do Servidor Público Municipal de Säo Paulo, relativos a 7.197 doentes internados no período de 6 meses (novembro 1983 a abril de 1984), encontrando incidência média mensal de 2,8%. Observou-se diminuiçäo no consumo de antimicrobianos (20,6%) no transcorrer do período de estudo, apesar do aumento verificado no número de internaçöes. O estudo dos gastos com internaçäo mostrou uma economia acumulada de Cr$26.378.619, equivalentes a 2.577 ORTN no período ou 429,5 ORTN mensais

Infecçöes hospitalares: diminuiçäo do consumo de antimicrobianos / Hospitalar infections: reduction of the antibiotics consumption

Estudou-se em 15.406 pacientes internados no Hospital do Servidor Público Municipal, de novembro de 1983 a novembro de 1984, divididos em dois semestres, a taxa de infecçäo comunitária, hospitalar, consumo de antibióticos por unidade e unidades de antibióticos por paciente. Constatou-se que sem alterar a incidência de infecçäo hospitalar houve reduçäo no consumo de antibióticos e aumento do número de pacientes internados

Infecçäo hospitalar: estudo realizado no Hospital do Servidor Público Municipal de Säo Paulo / Cross infection: study carried out at the Hospital do Servidor Público Municipal de Säo Paulo

Os autores estudaram as infecçöes hospitalares observadas no Hospital do Servidor Público Municipal de Säo Paulo relativas a 7.197 doentes internados. Levantaram os seguintes dados: taxas de saídas (altas/óbitos), patógenos isolados, procedência do material para exame bacteriológico e açäo dos antimicrobianos. Encontraram incidência de 11,2% para as infecçöes, sendo 2,8% adquiridas no hospital e 8,4% comunitárias. Verificaram ainda diminuiçäo no consumo dos antimicrobianos, apesar do aumento no número de doentes internados