Correlation between gene mutations and clinical characteristics in papillary thyroid cancer: a retrospective analysis of BRAF mutations and RET rearrangements.

INTRODUCTION: Activation of the MAPK pathway by genetic mutations (such as BRAF and RET) initiates and accelerates the growth of papillary thyroid carcinoma (PTC). However, the correlation between genetic mutations and clinical features remains to be established. Therefore, this study aimed to retrospectively analyze major genetic mutations, specifically BRAF mutations and RET rearrangements, and develop a treatment algorithm by comparing background and clinical characteristics. METHOD: One hundred thirteen patients with primary PTC were included in this study. BRAF mutations were detected via Sanger sequencing and RET rearrangements were detected via fluorescence in situ hybridization (FISH) analysis, and reverse transcription polymerase chain reaction (RT-PCR). The patients were categorized into two groups based on the presence of BRAF mutations and RET rearrangements and their clinical characteristics (age, sex, TNM, stage, extratumoral extension, tumor size, unifocal/multifocal lesions, vascular invasion, differentiation, chronic thyroiditis, preoperative serum thyroglobulin level, and 18F-fluorodeoxyglucose (FDG) uptake) were compared subsequently. RESULT: After excluding unanalyzable specimens, 80 PTC patients (22 males and 58 females, mean age: 57.2 years) were included in the study. RET rearrangements were positive in 8 cases (10%), and BRAF mutation was positive in 63 (78.6%). The RET rearrangement group was significantly associated with younger age (p = 0.024), multifocal lesion (p = 0.048), distant metastasis (p = 0.025) and decreased 18F-fluorodeoxyglucose uptake (p < 0.001). The BRAF mutation group was significantly associated with unifocal lesions (p = 0.02) and increased 18F-FDG uptake (p = 0.004). CONCLUSION: In this study, an increase in M classification cases was found in the RET rearrangements group. However, genetic mutations were not associated with the clinical stage, and no factors that could be incorporated into the treatment algorithm were identified.

Comparative prospective cohort study of efficacy and safety according to dosage and administration of ceftriaxone for community-acquired pneumonia.

INTRODUCTION: Limited prospective evidence has been accumulated regarding the efficacy and safety of ceftriaxone (CTRX) based on differences in dosage and administration of the drug as empiric therapy for community-acquired pneumonia (CAP). This study aimed to compare initial treatment failure, 30-day mortality, and side effects between two groups of hospitalized adult CAP patients: one receiving intravenous CTRX at 1g twice daily (1gq12hr) and the other receiving 2g once daily (2gq24hr). METHODS: We prospectively included patients with CAP admitted to our hospital between October 2010 and December 2018. We analyzed patients initially treated solely with CTRX as either 1gq12hr or 2gq24hr. The primary outcome was initial treatment failure, while secondary outcomes were 30-day mortality and side effects. Inverse probability of treatment weighting (IPTW) analysis was used to minimize biases. RESULTS: Among the 457 CAP patients, 186 patients were in the 1gq12hr group and 271 patients were in the 2gq24hr group. After IPTW analysis, no significant differences in initial treatment failure rate (2.43 % vs 4.46 %, p = 0.27) or 30-day mortality rate (2.95 % vs 6.43 %, p = 0.13) were seen between groups. A small but noteworthy tendency was noted in the frequency of side effects between the two groups (1.04 % vs 4.20 %, p = 0.08) following IPTW analysis, even though the difference was not significant. CONCLUSIONS: This study did not find any significant difference between ceftriaxone 1gq12hr and 2gq24hr regarding efficacy or safety in adult patients with CAP. However, CTRX 1gq12hr may represent a safer option in terms of side effects.

Phosphoribosyl pyrophosphate amidotransferase: Novel biomarker and therapeutic target for nasopharyngeal carcinoma.

Cancer cells show a dynamic metabolic landscape, requiring a sufficient supply of nucleotides to proliferate. They are highly dependent on de novo purine biosynthetic pathways for their nucleotide requirements. Phosphoribosyl pyrophosphate amidotransferase (PPAT), catalyzing the first step of de novo purine biosynthesis, is highly expressed in various cancers. We observed an increased expression of PPAT in nasopharyngeal carcinoma (NPC). Moreover, our ribonucleic acid sequencing analysis showed high PPAT expression in Epstein-Barr virus-positive NPC, which was supported by in vitro analysis. Through a gene knockdown study, we showed that the suppression of PPAT expression reduced the proliferation and invasion of NPC cells. We also demonstrated the regulation of PPAT by glutamine, a cosubstrate for PPAT. A glutamine antagonist, 6-diazo-5-oxo-L-norleucine, blocked glutamine-mediated induction of PPAT and reduced NPC cell proliferation. Immunohistochemical analysis of PPAT in NPC tissues revealed increased expression of PPAT with disease progression, which was significantly associated with poor prognosis. In summary, this study highlighted the biological function of PPAT in NPC, establishing its potential as a novel prognostic biomarker for aggressive NPC and a promising therapeutic target.

Diagnostic Usefulness of Liquid Culture Medium for Mycobacterium avium-intracellulare Complex Lung Disease: A Single-Centre, Retrospective Study.

Background The diagnosis of Mycobacterium avium-intracellulare complex lung disease (MAC-LD) requires two or more positive sputum cultures. Few reports have examined the usefulness of adding liquid culture to conventional solid culture for diagnosing MAC-LD. Methods A retrospective, cohort study of patients examined at Kurashiki Central Hospital in Japan with a confirmed diagnosis of MAC-LD between January 1, 2002, and June 20, 2021, was conducted. The primary endpoint was the culture positivity rate, which was compared between the liquid and Ogawa culture media in patients who underwent sputum culture using both methods. Secondary endpoints were the culture positivity rate in smear-positive specimens and the positivity rate by radiological type. Results The study, which involved 351 patients and 702 specimens, showed a higher positivity rate for liquid culture (n=690, 98.3%) than Ogawa culture (n=315, 44.9%). Overall, 265 patients (75.5%) would have had delayed MAC-LD diagnosis without liquid medium being used. Of the 95 smear-positive specimens, 71 (74.7%) were positive on both cultures, whereas 24 (25.3%) were positive only on liquid culture. The positivity rate of Ogawa culture varied by radiological type. Conclusions Liquid culture is more valuable for the early diagnosis of MAC-LD than Ogawa culture.

Association of 18F- fluorodeoxyglucose uptake with the expression of metabolism-related molecules in papillary thyroid cancer.

OBJECTIVES: 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) is a diagnostic imaging method that is based on the Warburg effect, which is the increased uptake of glucose through aerobic glycolysis in cancer cells. The diagnostic value of 18F-FDG-PET/CT for thyroid cancer is controversial. However, uptake of 18F-FDG and the corresponding maximum standardized uptake value (SUVmax) is expected to reflect the metabolic status of cancer cells. In the present study, we sought to determine the relationship between 18F-FDG uptake and tumor metabolism- associated factors. METHODS: This was a single-center retrospective study. In the present study, SUVmax was compared with the expression of hexokinase 2 (HK2), glucose transporter 1 (GLUT1), vascular endothelial growth factor (VEGF), and glutaminase 1 (GLS1) in 41 patients with thyroid cancer. RESULTS: GLS1 expression was found to be moderately correlated with SUVmax (p < 0.001, r = 0.51), whereas HK2 and VEGF expression were weakly correlated (p = 0.011, r = 0.28, p = 0.008, r = 0.29, respectively) and GLUT1 did not correlate with SUVmax (p = 0.62, r = 0.06). CONCLUSION: Our findings suggest 18F-FDG PET/CT reflects GLS1 expression in thyroid cancer and could be used to select suitable candidates for GLS1 inhibitor treatment.

Three cases of hospitalized Legionella pneumonia patients successfully treated with lascufloxacin.

Legionella pneumonia is one of the major causes of severe pneumonia, in which treatment delay might lead to a poor prognosis. Therefore, as far as possible, early diagnosis and treatment of Legionella pneumonia is essential. Regarding the antimicrobials for Legionella pneumonia, fluoroquinolones, such as levofloxacin, or macrolides, such as azithromycin (AZM), are recommended in Japan and other countries. Lascufloxacin (LSFX), the newest fluoroquinolone developed in Japan, has been in use in daily clinical practice since January 2020. However, there are only few reports of Legionella pneumonia cases treated with LSFX. Here, we report three cases of hospitalized Legionella pneumonia patients that were successfully treated using LSFX. All three patients were admitted to the medical ward on admission, although one patient was subsequently transferred to the ICU for mechanical ventilatory management due to worsening of the pneumonia on day 3. All patients improved and were discharged following LSFX treatment (the patient admitted to the ICU was treated using LSFX + AZM combination therapy) without any severe adverse events. LSFX might be considered to be the first antibiotic choice for Legionella pneumonia, similar to levofloxacin. However, further data regarding the treatment of Legionella pneumonia cases using LSFX are needed to evaluate its efficacy and safety.

Identification rate of Legionella species in non-purulent sputum culture is comparable to that in purulent sputum culture in Legionella pneumonia.

Many Legionella pneumonia patients do not produce sputum, and it is unknown whether purulent sputum is required for the identification of Legionella species. This study aimed to evaluate the identification rate of Legionella species based on sputum quality and the factors predictive of Legionella infection. This study included Legionella pneumonia patients at Kurashiki Central Hospital from November 2000 to December 2022. Sputum quality, based on gram staining, was classified as the following: Geckler 1/2, 3/6 and 4/5. Geckler 4/5 was defined as purulent sputum. The sputa of 104 of 124 Legionella pneumonia patients were cultured. Fifty-four patients (51.9%) were identified with Legionella species, most of which were Legionella pneumophila serogroup 1 (81.5%). The identification rates of Legionella species according to sputum quality were 57.1% (16/28) in Geckler 1/2 sputum, 50.0% (34/68) in Geckler 3/6 sputum, and 50.0% (4/8) in Geckler 4/5 sputum, which were not significantly different (P = 0.86). On multivariate analysis, pre-culture treatment with anti-Legionella antimicrobials (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.06-0.91), Pneumonia Severity Index class ≥IV (OR 2.57 [95% CI 1.02-6.71]), and intensive care unit admission (OR 3.08, 95% CI 1.06-10.09) correlated with the ability to identify Legionella species, but sputum quality did not (OR 0.88, 95% CI 0.17-4.41). The identification rate of Legionella species in non-purulent sputum was similar to that in purulent sputum. For the diagnosis of Legionella pneumonia, sputum should be collected before administering anti-Legionella antibiotics and cultured regardless of sputum quality.

Lymph node metastasis regulation by peritumoral tonsillar tissue mitochondria-related pathway activation in oropharyngeal cancer.

Immune-related gene expression profiles of peritumoral tonsillar tissues are modified by oropharyngeal cancer (OPC) nodal status. This study explored immunometabolism and immune cell count alterations in peritumoral tonsillar tissue according to OPC nodal status. Microarray data analysis of 27 peritumoral tonsillar tissue samples, using a newly generated mitochondrial metabolism-related gene set comprised of 948 genes, detected 228 differentially expressed genes (DEGs) (206 up- and 22 downregulated) in metastasis-negative cases compared to metastasis-positive ones. REACTOME pathway analysis of the 206 upregulated genes revealed the Toll-like receptor 4 cascade were most enriched. Immune cell proportion analysis using the CIBERSORTx algorithm revealed a significantly higher rate of naïve B cells, but lower rates of regulatory T cells and resting natural killer cells in metastasis-negative cases. Digital spatial profiling of the 6 OPC tissues detected 9 DEGs in the lymphoid regions, in contrast, no DEGs were identified in tumor regions according to nodal status. Cancer cell nests and pair matched normal epithelia mitochondrial DNA (mtDNA) from 5 OPC tissues were analyzed by next generation sequencing for variant detection. However, no significant mtDNA variation was found. This study identified mitochondria-related immune cell transcriptional programs and immune cell profiles associated with OPC lymphatic spread in peritumoral tonsil tissue, further evaluation of which will elucidate targetable immune mechanisms associated with OPC lymphatic dissemination.

Peritumoral SPARC expression induced by exosomes from nasopharyngeal carcinoma infected Epstein-Barr virus: A poor prognostic marker.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) cells have high metastatic potential. Recent research has revealed that the interaction of between tumor cells and the surrounding stroma plays an important role in tumor invasion and metastasis. In this study, we showed the prognostic value of expression of SPARC, an extracellular matrix protein with multiple cellular functions, in normal adjacent tissues (NAT) surrounding NPC. In the immunohistochemical analysis of 51 NPC biopsy specimens, SPARC expression levels were significantly elevated in the NAT of EBER (EBV-encoded small RNA)-positive NPC compared to that in the NAT of EBER-negative NPC. Moreover, increased SPARC expression in NAT was associated with a worsening of overall survival. The enrichment analysis of RNA-seq of publicly available NPC and NAT surrounding NPC data showed that high SPARC expression in NPC was associated with epithelial mesenchymal transition promotion, and there was a dynamic change in the gene expression profile associated with interference of cellular proliferation in NAT, including SPARC expression. Furthermore, EBV-positive NPC cells induce SPARC expression in normal nasopharyngeal cells via exosomes. Induction of SPARC in cancer-surrounding NAT cells reduced intercellular adhesion in normal nasopharyngeal structures and promoted cell competition between cancer cells and normal epithelial cells. These results suggest that epithelial cells loosen their own binding with the extracellular matrix as well as stromal cells, facilitating the invasion of tumor cells into the adjacent stroma by activating cell competition. Our findings reveal a new mechanism by which EBV creates a pro-metastatic microenvironment by upregulating SPARC expression in NPC.

Roll-to-Roll Printing of Anomalous Nernst Thermopile for Direct Sensing of Perpendicular Heat Flux.

The anomalous Nernst effect (ANE) converts heat flux perpendicular to the plane into electricity, in sharp contrast with the Seebeck effect (SE), enabling mass production, large area, and flexibility of their devices through ordinary thin-film fabrication techniques. Heat flux sensors, one of the most promising applications of ANE, are powerful devices for evaluating heat flow and can lead to energy savings through efficient thermal management. In reality, however, SE caused by the in-plane heat flux is always superimposed on the measurement signal, making it difficult to evaluate the perpendicular heat flux. Here, ANE-type heat flux sensors that selectively detect a perpendicular heat flux are fabricated by adjusting the net Seebeck coefficient in their thermopile circuit with mass-producible roll-to-roll sputtering methods. The direct sensing of perpendicular heat flux using ANE-based flexible thermopiles, as well as their simple fabrication process, paves the way for the practical application of thin-film thermoelectric devices.

Immune-Related Gene Expression Profile at Peritumoral Tonsillar Tissue Is Modified by Oropharyngeal Cancer Nodal Status.

Secondary lymphoid organs, such as lymph nodes and tonsils, serve as an interface between the immune system and tumor cells as an initial antigen-presentation site, crucial in antitumor immune response and disease progression. In oropharyngeal cancers originating from palatine tonsils, it was hypothesized that characterizing the immunologic process occurring in the peritumoral tonsil tissue would elucidate immune mechanisms of the lymphatic spread of the disease. A total of 33 patients were enrolled and divided into two cohorts. In Cohort 1 (6 patients), gene expression profiles at the peritumoral lymph regions and tumor regions were analyzed using the whole-transcriptome atlas. In the peritumoral lymph regions, 237 genes were up-regulated in metastasis-negative cases compared with metastasis-positive ones, but only 1 gene was up-regulated in tumor regions. In Cohort 2 (27 patients), microarray analysis of peritumoral tonsil tissue revealed 192 up-regulated genes. Gene ontology analysis revealed the significantly enriched Gene Ontology terms associated with T-cell activation; top 10 hub genes, as ranked by degree, were PTPRC, TLR4, CD80, CD40, STAT3, CD28, CD40LG, CD44, CCR7, and IL7R. Gene set enrichment analysis combined with principal component analysis were used to effectively classify patients as lymph node metastasis positive or negative. These findings suggest peritumoral tonsils as a potential target for investigating the immune mechanisms associated with the lymphatic spread of the disease in oropharyngeal cancers.

Air embolism after transbronchial lung cryobiopsy: A case report.

A 76-year-old woman underwent transbronchial lung cryobiopsy (TBLC) and transbronchial lung biopsy (TBLB) for examination of interstitial infiltrates. After the examination, the patient's consciousness became clouded, and head computed tomography showed an air embolus. She was started on 100% oxygen, and her consciousness improved, but she remained hemiplegic on the left side and dysphagic. Vascular air embolism (VAE) is a rare but serious complication. Although cases of VAE have been reported with conventional transbronchial forceps biopsy, cases of VAE after TBLC are quite rare, and thus this case is reported.

Addition of Baricitinib to COVID-19 Treatment Does Not Increase Bacterial Infection Compared to Standard Therapy: A Single-center Retrospective Study.

Objective The coronavirus disease 2019 (COVID-19) pandemic continues to spread across the world, and the utility of many drugs for treatment has been suggested. However, few studies have examined the efficacy and safety of treatment with baricitinib, remdesivir, and dexamethasone. Methods A retrospective, cohort study of patients who were admitted to Kurashiki Central Hospital in Japan between April 6 and June 29, 2021, was conducted. Differences in patients' background characteristics, clinical outcomes, and safety were investigated in the groups with and without baricitinib treatment. The primary outcome was the bacterial infection rate, and the secondary outcome was the 28-day mortality rate. An inverse probability of treatment weighting (IPTW) analysis, including 12 covariates, was used as a propensity score analysis to reduce biases. Results In total, there were 96 patients, including 43 in the baricitinib-containing therapy (BCT) group and 53 in the non-baricitinib-containing therapy (non-BCT) group. In the BCT group, the ordinal scale on admission was 2.3% with 4, 51.1% with 5, 23.3% with 6, and 23.3% with 7. In the non-BCT group, the ordinal scale was 1.9% with 3, 18.9% with 4, 58.5% with 5, 13.2% with 6, and 7.5% with 7. After adjusting by the IPTW analysis, the BCT group did not have an increased bacterial infection rate [odds ratio (OR), 1.1; 95% confidence interval (CI), 0.36-3.38; p=0.87] or 28-day mortality rate (OR, 0.31; 95% CI, 0.07-1.3; p=0.11) compared with the non-BCT group. Conclusion BCT can be administered without increasing the infection risk compared with non-BCT.

Protein Farnesylation on Nasopharyngeal Carcinoma, Molecular Background and Its Potential as a Therapeutic Target.

Nasopharyngeal carcinoma (NPC) is one of the Epstein-Barr virus (EBV)-associated malignancies. NPC is highly metastatic compared to other head and neck carcinomas, and evidence has shown that the metastatic features of NPC are involved in EBV infection. The prognosis of advanced cases, especially those with distant metastasis, is still poor despite advancements in molecular research and its application to clinical settings. Thus, further advancement in basic and clinical research that may lead to novel therapeutic modalities is needed. Farnesylation is a lipid modification in the C-terminus of proteins. It enables proteins to attach to the lipid bilayer structure of cellular membranes. Farnesylation was initially identified as a key process of membrane association and activation of the RAS oncoprotein. Farnesylation is thus expected to be an ideal therapeutic target in anti-RAS therapy. Additionally, more and more molecular evidence has been reported, showing that proteins other than RAS are also farnesylated and have significant roles in cancer progression. However, although several clinical trials have been conducted in cancers with high rates of ras gene mutation, such as pancreatic carcinomas, the results were less favorable than anticipated. In contrast, favorable outcomes were reported in the results of a phase II trial on head and neck carcinoma. In this review, we provide an overview of the molecular pathogenesis of NPC in terms of the process of farnesylation and discuss the potential of anti-farnesylation therapy in the treatment of NPC.

Estrogen induces the expression of EBV lytic protein ZEBRA, a marker of poor prognosis in nasopharyngeal carcinoma.

Several epidemiological studies have suggested that Epstein-Barr virus (EBV) lytic infection is essential for the development of nasopharyngeal carcinoma (NPC), as the elevation of antibody titers against EBV lytic proteins is a common feature of NPC. Although ZEBRA protein is a key trigger for the initiation of lytic infection, whether its expression affects the prognosis and pathogenesis of NPC remains unclear. In this study, 64 NPC biopsy specimens were analyzed using immunohistochemistry. We found that ZEBRA was significantly associated with a worsening of progression-free survival in NPC (adjusted hazard ratio, 3.58; 95% confidence interval, 1.08-11.87; p = 0.037). Moreover, ZEBRA expression positively correlated with key endocrinological proteins, estrogen receptor α, and aromatase. The transcriptional level of ZEBRA is activated by estrogen in an estrogen receptor α-dependent manner, resulting in an increase in structural gene expression levels and extracellular virus DNA copy number in NPC cell lines, reminiscent of lytic infection. Interestingly, it did not suppress cellular proliferation or increase apoptosis, in contrast with cells treated with 12-O-tetradecanoylphorbol-13-acetate and sodium butyrate, indicating that viral production induced by estrogen is not a cell lytic phenomenon. Our results suggest that intratumoral estrogen overproduced by aromatase could induce ZEBRA expression and EBV reactivation, contributing to the progression of NPC.

EBV genome variations enhance clinicopathological features of nasopharyngeal carcinoma in a non-endemic region.

Nasopharyngeal carcinoma (NPC) is caused by infection with Epstein-Barr virus (EBV) and endemic in certain geographic regions. EBV lytic gene, BALF2, closely associates with viral reactivation and BALF2 gene variation, the H-H-H strain, causes NPC in endemic region, southern China. Here, we investigate whether such EBV variations also affect NPC in a non-endemic region, Japan. Viral genome sequencing with 47 EBV isolates of Japanese NPC were performed and compared with those of other EBV-associated diseases from Japan or NPC in Southern China. EBV genomes of Japanese NPC are different from those of other diseases in Japan or endemic NPC; Japanese NPC was not affected by the endemic strain (the BALF2 H-H-H) but frequently carried the type 2 EBV or the strain with intermediate risk of endemic NPC (the BALF2 H-H-L). Seven single nucleotide variations were specifically associated with Japanese NPC, of which six were present in both type 1 and 2 EBV genomes, suggesting the contribution of the type 2 EBV-derived haplotype. This observation was supported by a higher viral titer and stronger viral reactivation in NPC with either type 2 or H-H-L strains. Our results highlight the importance of viral strains and viral reactivation in the pathogenesis of non-endemic NPC.

Low-carbon economic dispatch considering integrated demand response and multistep carbon trading for multi-energy microgrid.

With the rapid development of distributed energy resources and natural gas power generation, multi-energy microgrid (MEMG) is considered as a critical technology to increase the penetration of renewable energy and achieve the target of carbon emission reduction. Therefore, this paper proposes a low-carbon economic dispatch model for MEMG to minimize the daily operation cost by considering integrated demand response (IDR) and multistep carbon trading. Specifically, IDR operation includes shifting of shiftable electric load, adjusting of flexible thermal load and cooling load, and it is employed to decrease operation cost. Besides, the multistep carbon trading means that different carbon trading prices correspond to different carbon trading volumes, which is applied to stringently restrict carbon emission. The simulation results show that the proposed model can effectively reduce the carbon emission while greatly decrease the operation cost.

Inflammatory biomarkers are not useful for predicting prognosis in nursing and healthcare-associated pneumonia: A prospective, cohort study.

INTRODUCTION: Whether inflammatory biomarkers including procalcitonin (PCT) and C-reactive protein (CRP) are useful for predicting prognosis in nursing and healthcare-associated pneumonia (NHCAP) is unknown. The aim of the present study was to investigate the utility of serial PCT and CRP measurements for predicting prognosis and treatment efficacy for hospitalized NHCAP patients. METHODS: This prospective, observational, cohort study enrolled consecutive NHCAP patients hospitalized at Kurashiki Central Hospital from October 2010 to September 2017. PCT and CRP were measured twice, once on admission and again within 48-72 h after admission. The primary outcome was 30-day all-cause mortality, and the secondary outcome was initial treatment failure. RESULTS: A total of 299 patients were included. The 30-day mortality rate was 8.4% (25/299), and the initial treatment failure rate was 15.4% (46/299). On multivariate analysis, performance status [odds ratio (OR) (95% confidence interval (CI)): 2.25 (1.34-3.77), P = 0.002], temperature [OR (95%CI): 0.53 (0.32-0.88), P = 0.02], heart rate [OR (95%CI): 1.03 (1.01-1.06), P = 0.007], albumin [OR (95%CI): 0.42 (0.18-0.95), P = 0.04], and blood urea nitrogen [OR (95%CI): 1.02 (1.00-1.05), P = 0.04] were significant prognostic factors, and CRP D3 [OR (95%CI): 1.07 (1.02-1.11), P = 0.003] and PSI [OR (95%CI): 1.01 (1.00-1.02), P = 0.01] were the predictors of initial treatment failure. Consecutive measurements of PCT and CRP were not significant predictors of 30-day mortality. CONCLUSIONS: Inflammatory biomarkers including PCT and CRP were not useful for predicting prognosis and treatment efficacy in NHCAP patients. We should carefully evaluate the patients' vital signs and comorbidities when managing NHCAP patients.

Hypothyroidism as an immune-related adverse event caused by atezolizumab in a patient with muscle spasms: a case report.

A 60-year-old man with a history of 4 cycles of atezolizumab treatment for non-small cell lung cancer presented to our hospital with a chief complaint of proximal muscle-dominant spasms. Blood tests showed elevated creatine phosphokinase (CPK) of 8450 U/L and hypothyroidism. There was little improvement even after stopping levetiracetam and pregabalin, and no subspinous physical findings of myositis. After levothyroxine was started for hypothyroidism, his muscle cramps and serum CPK level improved. Hypothyroidism as an immune-related adverse event can cause muscle spasms and is important in the differential diagnosis of muscle spasms in patients treated with immune checkpoint inhibitors.