Risk Factors for Bloodstream Infection in Patients Receiving Peripheral Parenteral Nutrition.

Background Intravenous fluid therapy, including peripheral parenteral nutrition (PPN), administered via a peripheral intravenous catheter (PVC) can occasionally lead to bloodstream infections (BSIs). PPN may thus be a risk factor for PVC-related BSI (PVC-BSI). However, the risk factors and incidence of PVC-BSI have not been previously reported, and evidence for these conditions remains unclear. Methods We retrospectively collected data from 391 patients who underwent PPN therapy with PVC at the Fukujuji Hospital from August 2022 to November 2023. We compared 20 patients who developed BSI during PPN therapy (BSI group) with 371 who did not develop BSI during PPN therapy (no-infection group). Results The incidence rate of PVC-BSI during PPN therapy was 5.1%. The BSI group had a significantly longer average daily infusion time of PPNs (median 24.0 [range 6.0-24.0] h vs. 6.0 [2.0-24.0] h, p<0.001) and of all intravenous fluids (median 24.0 [range 8.8-24.0] h vs. 10.3 [2.0-24.0] h, p<0.001) than the no infection group. An average daily infusion time of PPNs ≥12.0 h and an average daily infusion time of intravenous fluids ≥18.0 h were identified as predictive risk factors for BSI. When both risk factors were present, the sensitivity, specificity, and odds ratio for the development of BSI were 85.0%, 83.2%, and 27.9, respectively. Conclusion This study identified the incidence of and risk factors for developing BSI, such as a longer average daily infusion time of PPNs and all intravenous fluids, in patients receiving PPN therapy.

Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain Positive for the Panton-Valentine Leucocidin Gene in a Middle-Aged Patient With Multiple Septic Pulmonary Emboli.

A 59-year-old man suffered from fever and chest pain for three days following an accidental bite to a lip ulcer. His lower lip showed swelling and tenderness, and chest computed tomography showed multiple bilateral nodules. He was diagnosed with septic pulmonary embolism and a lip abscess, and blood, sputum, and lip abscess cultures confirmed the presence of methicillin-resistant Staphylococcus aureus (MRSA). Despite the initiation of vancomycin, he rapidly developed respiratory failure and septic shock, necessitating intubation and noradrenaline support. Gentamicin was added on the seventh day of admission due to an insufficient effect, and vancomycin was switched to linezolid on the 14th day of admission. However, his respiratory failure persisted as bilateral pneumothorax developed. Blood culture was negative on the 14th day after admission, but the patient died on the 15th day after admission. The MRSA isolate was tested for the presence of the Panton-Valentine leukocidin (PVL) gene in conjunction with the USA300 strain. The prevalence of community-acquired (CA)-MRSA in the USA300 clone is increasing but still low in Japan, and this type of infection is commonly observed in people of all ages; this case is the first instance reported in Japan of a middle-aged patient with septic pulmonary embolism. Given the anticipated global increase in CA-MRSA infection caused by the USA300 clone and the emergence of USA300 with altered pathogenicity, it may be crucial to suspect PVL-positive CA-MRSA infections even in middle-aged or elderly patients presenting with septic pulmonary embolism as community infections.

Prognostic value of serum tartrate­resistant acid phosphatase­5b for bone metastasis in patients with resectable breast cancer.

Bone metastasis significantly affects the quality of life of patients with metastatic breast cancer, and can shorten overall survival. Identifying patients with early-stage breast cancer at high risk for bone metastasis and preventing bone metastasis may lead to a better quality of life and prolonged survival. The present study investigated whether serum tartrate-resistant acid phosphatase-5b (TRACP-5b), a bone turnover marker, can be a prognostic factor for bone metastasis. Female patients who underwent resectable breast surgery between May 2002 and August 2006 were consecutively investigated. A total of 304 patients with a median follow-up of 3,722 days were retrospectively analyzed. TRACP-5b levels in sera prepared from patients' blood drawn preoperatively without any presurgical treatments were measured using an enzyme-linked immunosorbent assay. The cutoff of TRACP-5b levels, in order to separate patients into high and low TRACP-5b groups, was set at median (347 mU/dl). The associations of clinicopathological factors, including TRACP-5b, with bone metastasis-free interval (BMFI), which was defined as the duration between surgery and the diagnosis of bone metastasis at any time point, were examined. Multivariate analysis of various clinicopathological features revealed that lymph node metastasis and histological grade were independent factors associated with BMFI (P=0.017 and 0.030, respectively). In patients with node-positive breast cancer (n=114), a high TRACP-5b level and a high grade were significantly and independently associated with worse BMFI (log-rank P=0.041 and 0.011, respectively). In conclusion, these findings indicated that TRACP-5b may predict bone metastasis in patients with node-positive breast cancer.

High HER2 Intratumoral Heterogeneity Is a Predictive Factor for Poor Prognosis in Early-Stage and Locally Advanced HER2-Positive Breast Cancer.

PURPOSE: Breast cancer tumors frequently have intratumoral heterogeneity (ITH). Tumors with high ITH cause therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to a poor prognosis for HER2-targeted adjuvant therapy resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with the HER2 gene copy number within a tumor sample. Each tumor was classified into a biphasic grade graph (high heterogeneity [HH]) group or a monophasic grade graph (low heterogeneity [LH]) group based on heterogeneity. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: p < 0.001 (HH:63% vs. LH:91% at 10 years) and for the OS: p = 0.012 (HH:78% vs. LH:95% at 10 years). CONCLUSIONS: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach to heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

Pseudo-Meigs' Syndrome With Eosinophilic Pleural Effusion.

We present a rare case of a 45-year-old woman with pseudo-Meigs' syndrome and eosinophilic pleural effusion (EPE). She experienced cough, sputum, and dyspnea with a large right pleural effusion. Laboratory tests showed eosinophilia in the blood and pleural fluid. An ovarian tumor and ascites were also detected. After left salpingo-oophorectomy, the tumor was diagnosed as a mature cystic teratoma of the left ovary. The right-sided pleural effusion gradually resolved. Pseudo-Meigs' syndrome is characterized by benign ovarian tumor, ascites, and pleural effusion. Typically, it is associated with exudate pleural effusion characterized by a predominance of mononuclear cells. The occurrence of eosinophilic pleural effusion in our patient may be exceptionally rare.

Predictive factors of the presence of pulmonary embolism in patients with interstitial lung disease: Observational study.

In patients with interstitial lung disease (ILD), the risk of pulmonary embolism (PE) is increased; however, distinguishing between PE and ILD exacerbation can be difficult. Therefore, this study investigated the usefulness of the Wells criteria and revised Geneva score and predictive factors for diagnosing PE in ILD patients with worsening respiratory symptoms. We retrospectively collected the data of 65 patients with ILD who underwent computed tomography pulmonary angiography at Fukujuji Hospital and Kyorin University Faculty of Medicine from January 2018 to March 2023, including 18 patients in the PE group and 47 patients in the non-PE group, and the data were compared between the 2 groups. The Wells score (P = .165) and revised Geneva score (P = .140) were not useful for distinguishing between the PE and non-PE groups. Patients in the PE group showed higher D-dimer, total protein (TP), and globulin levels than those in the non-PE group (D-dimer median 24.5 µg/mL [range 3.0-79.3] vs 9.3 µg/mL [range 0.5-80.8], P = .016; TP median 7.2 g/dL [range 5.1-8.7] vs 6.4 g/dL [range 5.0-8.2], P = .002; globulin median 3.8 g/dL [range 2.6-5.5] vs 3.2 g/dL [range 3.0-5.3], P = .041). Using cutoff values of TP ≥ 7.0 g/dL and D-dimer ≥ 11.8 µg/mL, the odds ratios for predicting PE were 10.5 and 4.90, respectively. This study demonstrates that high TP and D-dimer levels are useful indicators for predicting PE in ILD patients with worsening respiratory symptoms, while the Wells score and revised Geneva score are not reliable in diagnosing PE.

Video gamers demonstrate superior bronchoscopy skills among beginners.

While previous research has explored the connection between video gaming and medical procedures, studies on the connection between video gaming and bronchoscopy techniques are lacking. This study aimed to investigate how video gaming experience influences bronchoscopy skills, particularly among beginners. This study was conducted at Fukujuji Hospital from January 2021 to October 2023. Twenty-three participants were assigned to the inexperienced group, and eighteen participants were assigned to the experienced group. The observational time during bronchoscopy, measured using a simulator, and the playing time of SPLATOON 2 (NINTENDO Co. Ltd., Japan) were analyzed. Video gaming skills were assessed based on game completion time, with shorter times indicating faster task completion. Participants were also divided into gamer and nongamer subgroups for further comparisons. A moderate linear relationship existed between bronchoscopic observation time and game completion time in the inexperienced group (r = 0.453, p = 0.030). However, no correlation was found in the experienced group (r = 0.268, p = 0.283). Among the inexperienced group, the gamer subgroup (n = 12) exhibited significantly shorter bronchoscopic observation times than did the nongamer subgroup (n = 11) (median [range]: 200 [129-229] s) vs. 281 [184-342] s, p = 0.005). This study demonstrated a relationship between bronchoscopy technique and video gaming skills among individuals with little bronchoscopy experience.

Activities of Daily Living, Hypoxemia, and Lymphocytes Score for Predicting Mortality Risk in Patients With Pulmonary TB.

BACKGROUND: A clinically applicable mortality risk prediction system for pulmonary TB may improve treatment outcomes, but no easy-to-calculate and accurate score has yet been reported. The aim of this study was to construct a simple and objective disease severity score for patients with pulmonary TB. RESEARCH QUESTION: Does a clinical score consisting of simple objective factors predict the mortality risk of patients with pulmonary TB? STUDY DESIGN AND METHODS: The data set from our previous prospective study that recruited patients newly diagnosed with pulmonary TB was used for the development cohort. Patients for the validation cohort were prospectively recruited between March 2021 and September 2022. The primary end point was all-cause in-hospital mortality. Using Cox proportional hazards regression, a mortality risk prediction model was optimized in the development cohort. The disease severity score was developed by assigning integral points to each variate. RESULTS: The data from 252 patients in the development cohort and 165 patients in the validation cohort were analyzed, of whom 39 (15.5%) and 17 (10.3%), respectively, died in the hospital. The disease severity score (named the AHL score) included three clinical parameters: activities of daily living (semi-dependent, 1 point; totally dependent, 2 points); hypoxemia (1 point), and lymphocytes (< 720/µL, 1 point). This score showed good discrimination with a C statistic of 0.902 in the development cohort and 0.842 in the validation cohort. We stratified the score into three groups (scores of 0, 1-2, and 3-4), which clearly corresponded to low (0% and 1.3%), intermediate (13.5% and 8.9%), and high (55.8% and 39.3%) mortality risk in the development and validation cohorts. INTERPRETATION: The easy-to-calculate AHL disease severity score for patients with pulmonary TB was able to categorize patients into three mortality risk groups with great accuracy. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Center; No. UMIN000012727 and No. UMIN000043849; URL: www.umin.ac.jp.

Diagnostic flowchart for tuberculous pleurisy, pleural infection, and malignant pleural effusion.

BACKGROUND: Several markers for the diagnosis of pleural effusion have been reported; however, a comprehensive evaluation using those markers has not been performed. Therefore, this study aimed to develop a diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases by using these markers. METHODS: We retrospectively collected data from 174 patients with tuberculous pleurisy, 215 patients with pleural infection other than tuberculous pleurisy, 360 patients with malignant pleural effusion, and 209 patients with other diseases at Fukujuji Hospital from January 2012 to October 2022. The diagnostic flowchart for four diseases was developed by using several previously reported markers. RESULTS: The flowchart was developed by including seven markers: pleural ADA ≥40 IU/L, pleural fluid LDH <825 IU/L, pleural fluid ADA/TP < 14, neutrophil predominance or cell degeneration, peripheral blood WBC ≥9200/µL or serum CRP ≥12 mg/dL, pleural amylase ≥75 U/L, and the presence of pneumothorax according to the algorithm of a decision tree. The accuracy ratio of the flowchart was 71.7 % for the diagnosis of the four diseases, with 79.3 % sensitivity and 75.4 % positive predictive value (PPV) for tuberculosis pleurisy, 75.8 % sensitivity and 83.2 % PPV for pleural infection, 88.6 % sensitivity and 68.8 % PPV for malignant pleural effusion, and 33.0 % sensitivity and 60.0 % PPV for other diseases in the flowchart. The misdiagnosis ratios were 4.6 % for tuberculosis pleurisy, 6.8 % for pleural infection, and 8.3 % for malignant pleural effusion. CONCLUSION: This study developed a useful diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases.

Evaluation of RASSF1A methylation in the lysate of sentinel lymph nodes for detecting breast cancer metastasis: A diagnostic accuracy study.

The restriction enzyme-based digital methylation-specific polymerase chain reaction (RE-dMSP) assay is useful for diagnosing sentinel lymph node (SN) metastasis in patients with breast cancer, by detecting tumor-derived methylated Ras association domain-containing protein 1 (RASSF1A). In addition, this assay has high concordance (95.0%) with one-step nucleic acid amplification (OSNA). The present study aimed to perform RE-dMSP using OSNA lysate from more patients and to re-evaluate its clinical usage. Overall, 418 SNs from 347 patients were evaluated using both OSNA and RE-dMSP. The concordance rate was 83.3% (348/418). RASSF1A methylation of the primary tumors was negative in 36 patients. When these patients were excluded, the concordance rate improved to 88.2% (330/374). Of the 79 OSNA-negative cases, 19 were RE-dMSP-positive, although all were positive for cytokeratin 19 expression in the primary tumor, suggesting that RE-dMSP can detect tumor-derived DNA with a higher sensitivity. The percent of methylated reference of the breast tumors showed a wide variety in the 16 OSNA-positive/RE-dMSP-negative cases, and such variability of methylation could have affected the results in these patients. In conclusion, although RE-dMSP can diagnose SN metastasis with high sensitivity and accuracy, and can be a supplementary tool to OSNA in breast cancer, RE-dMSP showed certain discordance with OSNA and critically depended on the absence or heterogeneity of DNA methylation in breast tumors. Further research is expected to develop an assay targeting other DNA alterations, such as mutations.

Analysis of the utility of transbronchial lung biopsy culture under endobronchial ultrasonography with a guide-sheath.

Transbronchial lung biopsy (TBLB) culture is not common in clinical practice, and TBLB culture for patients with mycobacterial disease provide limited value because the diagnostic accuracy of TBLB culture is very low. Recently, bronchoscopic devices have been further developed, such as endobronchial ultrasonography with a guide-sheath (EBUS-GS). Therefore, this study investigated the utility of TBLB culture obtained by using EBUS-GS compared to washing cultures. A total of 31 patients who underwent TBLB culture by using EBUS-GS (GS-TBLB) were collected retrospectively at Fukujuji Hospital from January 2018 to December 2022. The diagnostic accuracies of GS-TBLB culture and bronchial and device washing cultures (namely, washing culture) were compared. The patients comprised 13 individuals with nontuberculous mycobacteriosis, 7 with pulmonary aspergillosis, 6 with lung abscess, and 5 with pulmonary tuberculosis. The diagnostic accuracy of GS-TBLB culture was lower to that of TBLB culture than those of washing culture (n = 11 [35.5%] vs. n = 20 [64.5%], p = 0.016), and there was only one patient with positive GS-TBLB culture results and negative washing culture results. Comparing between patients with mycobacteria and non-mycobacteria, GS-TBLB culture positivity were no significant difference between patients with mycobacteria and non-mycobacteria (n = 6 [33.3%] vs. n = 5 [38.5%], p = 1.000), however, patients with mycobacteria diagnosed by washing culture more than those with non-mycobacteria (n = 15 [83.3%] vs. n = 5 [38.5%], p = 0.021). Our results demonstrate that the utility of TBLB culture for the diagnosis of pulmonary infections might provide limited value even if EBUS-GS is performed and lung tissue is successfully obtained.

Comparison of the thickness of the erector spinae muscles between aspiration pneumonia and bacterial pneumonia patients.

BACKGROUND AND AIMS: Aspiration pneumonia is generally associated with deterioration of skeletal muscle mass, which is usually evaluated by the erector spinae muscle cross-sectional area (ESMCSA); however, no report has assessed ESMCSA in patients with aspiration pneumonia. Furthermore, erector spinae muscle thickness (ESMT) was developed to be easier to measure than ESMCSA. Therefore, this study investigated the relationship between ESMT and ESMCSA in aspiration pneumonia patients compared to bacterial pneumonia patients. METHODS: We retrospectively collected data for 164 patients with aspiration pneumonia and 480 patients with bacterial pneumonia who were hospitalized at Fukujuji Hospital between September 2018 and May 2022. We assessed the correlations between ESMCSA and ESMT and compared the data between the two groups. RESULTS: ESMT had a strong, proportional relationship with ESMCSA in all patients (r = 0.908, p < 0.001) and those with aspiration pneumonia (r = 0.896, p < 0.001). ESMCSA (median 671.8 mm2 [range 164.0-1636.7] vs. median 1057.0 mm2 [range 161.3-2412.5], p < 0.001) and ESMT (median 17.1 mm [range 6.95-34.4] vs. median 23.8 mm [range 6.95-43.7], p < 0.001) were significantly lower in patients with aspiration pneumonia. A multivariate analysis of aspiration pneumonia diagnosis showed significant independent differences from bacterial pneumonia in ESMCSA (odds ratio 0.998 [95% CI: 0.996-0.999], p = 0.001) and ESMT (odds ratio 0.90 [95% CI: 0.84-0.96], p = 0.002). CONCLUSION: This study demonstrates a strong correlation between ESMCSA and ESMT. ESMT can be more easily used to evaluate skeletal muscle mass and can help in diagnosing aspiration pneumonia.

Detection of high-risk patients resistant to CDK4/6 inhibitors with hormone receptor-positive HER2-negative advanced and metastatic breast cancer in Japan (KBCSG-TR-1316).

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve the prognosis of hormone receptor-positive HER2-negative advanced/metastatic breast cancer (HR+/HER2- mBC). However, some cancers show resistance to CDK4/6i and have a poor prognosis. The non-luminal disease score (NOLUS) was developed to predict non-luminal disease using immunohistochemical analysis. METHODS: The association between the efficacy of CDK4/6i and NOLUS was investigated by evaluating pathological and clinical data, including real-world progression-free survival (rw-PFS) and overall survival (OS). Real-world data of patients with HR+/HER2- mBC who received CDK4/6i therapy [palbociclib or abemaciclib] as first- or second-line endocrine treatments was obtained. NOLUS was calculated using the formula: NOLUS (0-100) = - 0.45 × estrogen receptor (ER) (%) - 0.28 × progesterone receptor (PR) (%) + 0.27 × Ki67(%) + 73, and the patients were divided into two groups: NOLUS-positive (≥ 51.38) and NOLUS-negative (< 51.38). RESULTS: Of the 300 patients, 28 (9.3%) were NOLUS-positive, and 272 (90.7%) were NOLUS-negative. The expression rates (%) of ER and PgR in NOLUS-positive patients were lower than those in NOLUS-negative patients (p < 0.001). Ki67 expression was higher in NOLUS-positive patients. There were statistically significant differences in prognosis (rw-PFS and OS) between the two groups. Moreover, NOLUS-negative patients showed statistically better rw-PFS with first-line therapy than second-line therapy. However, NOLUS-positive patients showed poor prognoses with both the first and second therapeutic lines, suggesting CDK4/6i inefficacy for NOLUS-positive patients. CONCLUSIONS: The efficacy and prognosis of CDK4/6i significantly differed between the NOLUS-positive and NOLUS-negative patients. This feasible method can predict patients with HR+/HER2- mBC resistant to CDK4/6i and help select a better therapeutic approach to overcome resistance.

Spontaneous resolution of cryptogenic organizing pneumonia: Observational study.

Cryptogenic organizing pneumonia (COP) is an idiopathic interstitial pneumonia generally requiring steroid therapy, and spontaneous resolution has been reported in patients with mild disease. However, evidence supporting the need for COP treatment is poor. Therefore, we investigated the characteristics of patients with spontaneous resolution. We retrospectively collected data from 40 adult patients who were diagnosed with COP through bronchoscopic examination at Fukujuji Hospital from May 2016 to June 2022. Sixteen patients who improved without steroid therapy (the spontaneous resolution group) and 24 patients who required steroid therapy (the steroid therapy group) were compared. Patients in the spontaneous resolution group showed a lower C-reactive protein (CRP) concentration (median 0.93 mg/dL [interquartile range [IQR] 0.46-1.91] vs median 10.42 mg/dL [4.82-16.7], P < .001), a higher lymphocyte ratio (median 21.7% [18.2-25.2] vs median 13.3% [8.8-19.8], P = .002), and a longer duration from symptom onset to diagnosis of COP (median 51.5 days [24.5-65.3] vs 23.0 days [17.3-31.8], P = .009) than those in the steroid therapy group. Within 2 weeks, all patients in the spontaneous resolution group showed relief of symptoms and alleviated radiographic findings. The area under the receiver operating characteristic (ROC) curve was 0.859 (95% confidence interval [CI]: 0.741-0.978) in CRP. When we arbitrarily determined the cutoff values, including CRP levels of ≤3.79 mg/dL, the sensitivity, specificity, and odds ratio were 73.9%, 93.8%, and 39.8 (95% confidence interval: 4.51-1968.9), respectively. Only 1 patient in the spontaneous resolution group showed recurrence but did not require steroid therapy. Conversely, 4 patients in the steroid therapy group showed recurrence and were treated by an additional course of steroids. The characteristics of COP with spontaneous resolution and factors that determine the patients in whom steroid therapy might be avoided is detailed in this study.

Relationship between the thickness of erector spinae muscles and mortality in patients with pulmonary tuberculosis.

BACKGROUND: Skeletal muscle mass is a known predictor of mortality in older patients. However, its relationship with tuberculosis is unclear. Skeletal muscle mass is determined by the cross-sectional area of erector spinae muscle (ESMCSA). Additionally, the erector spinae muscle thickness (ESMT) is an easier measurement than ESMCSA. This study investigated the relationship of ESMT and ESMCSA with mortality in tuberculosis patients. METHODS: We retrospectively collected the data of 267 older patients (age ≥65 years) who were hospitalized due to tuberculosis at the Fukujuji Hospital from January 2019 to July 2021. This included 40 patients with 60-day mortality (the death group) and 227 patients with 60-day survival (the alive group). Here, we assessed the correlations between ESMCSA and ESMT, and the data were compared between the two groups. RESULTS: ESMT had a strong proportional relationship with ESMCSA (r = 0.991, p < 0.001). ESMCSA (median 670.2 mm2 [interquartile range (IQR): 585.1-760.9] vs. 914.3 mm2 [717.6-1141.6], p < 0.001) and ESMT (median 16.7 mm [15.4-18.6] vs. 21.1 mm [18.0-25.5], p < 0.001) were significantly lower in the patients in the death group than those of patients in the alive group. A multivariable Cox proportional hazard model for 60-day mortality showed significantly independent differences in ESMT (hazard ratio [HR] 0.870 [95% confidence interval (Cl): 0.795-0.952], p = 0.003) and ESMCSA (HR 0.998 [95% Cl: 0.996-0.999], p = 0.009). CONCLUSIONS: This study demonstrated a strong correlation between ESMCSA and ESMT, which were risk factors for mortality in patients with tuberculosis. Therefore, using ESMT is easier to predict mortality than ESMCSA.

Detection of Ultra-Rare ESR1 Mutations in Primary Breast Cancer Using LNA-Clamp ddPCR.

ESR1 mutations in breast cancer are one of the mechanisms of resistance to aromatase inhibitors. These mutations are common in metastatic breast cancer; however, these are rare in primary breast cancer. However, these data have been analyzed mainly in formalin-fixed, paraffin-embedded tissue; thus, rare mutations that may be present in primary breast cancer may be overlooked. In this study, we developed a highly sensitive mutation detection method called locked nucleic acid (LNA)-clamp droplet digital PCR (ddPCR) and validated it. The mutation detection sensitivity was substantiated to 0.003%. Then, we used this method to analyze ESR1 mutations in fresh-frozen (FF) tissues of primary breast cancer. cDNA extracted from the FF tissues of 212 patients with primary breast cancers were measured. Twenty-eight ESR1 mutations were found in twenty-seven (12.7%) patients. Sixteen (7.5%) patients had Y537S mutations and twelve (5.7%) had D538G mutations. Two mutations with a variant allele frequency (VAF) of ≥0.1% and twenty-six mutations with a VAF of <0.1% were found. By using this LNA-clamp ddPCR, this study demonstrated the presence of minor clones with a VAF of <0.1% in primary breast cancer.

Usefulness of gastric aspirates for diagnosing nontuberculous mycobacteriosis.

Distinguishing between nontuberculous mycobacterial pulmonary disease (NTM-PD) and pulmonary tuberculosis (TB) is difficult. We aimed to evaluate the usefulness of gastric aspirate examination for NTM-PD diagnosis and for differentiating NTM-PD from other diseases, including pulmonary TB. We retrospectively collected data for 491 patients with negative sputum smears or a lack of sputum production at Fukujuji Hospital. We compared 31 patients with NTM-PD to 218 patients with other diseases (excluding 203 with pulmonary TB). Additionally, we compared 81 patients with NTM cultured from at least one sputum or bronchoscopy sample to the other 410 patients. Gastric aspirate examination for NTM-PD diagnosis showed 74.2% sensitivity and 99.0% specificity for culture positivity. There was no significant difference between the nodular bronchiectatic disease and cavitary disease types for culture positivity (p = 0.515). The significance of NTM isolation from gastric aspirate showed 64.2% sensitivity and 99.8% specificity for culture positivity. Gastric aspirate examination revealed NTM in one TB patient, allowing TB to be ruled out in 98.1% of patients with NTM cultured from gastric aspirates. Gastric aspirate examination is helpful for early-stage NTM diagnosis and ruling out pulmonary TB. This could lead to more accurate and timely treatment.

Characteristics of pleural effusion due to paradoxical response in patients with pulmonary tuberculosis.

BACKGROUND: Patients with pulmonary tuberculosis may present with deterioration of pleural effusion during anti-tuberculosis therapy, referred to as a paradoxical response (PR), with some patients requiring additional intervention. However, PR may be confused with other differential diagnoses, and the predictive factors for recommending additional therapies are unknown. Therefore, this study aimed to reveal useful information for the diagnosis and intervention of PR. METHODS: Data from human immunodeficiency virus-negative patients with tuberculous pleurisy (n = 210), including 184 patients with pre-existing pleural effusion and 26 patients with PR at Fukujuji Hospital, were retrospectively collected from January 2012 to December 2022 and compared. Furthermore, patients with PR were divided into the intervention group (n = 9) and the no intervention group (n = 17) and were compared. RESULTS: Patients in the PR group had lower pleural lactate dehydrogenase (LDH) (median 177 IU/L vs. 383 IU/L, p < 0.001) and higher pleural glucose (median 122 mg/dL vs. 93 mg/dL, p < 0.001) levels than those in the preexisting pleural effusion group. Other pleural fluid data were not significantly different. Patients in the intervention group had a shorter duration from the initiation of anti-tuberculosis therapy to the development of PR than patients in the no intervention group (median 19.0 days [interquartile range (IQR): 18.0-22.0] vs. median 37.0 days [IQR: 28.0-58.0], p = 0.012). CONCLUSION: This study demonstrates that, apart from lower pleural LDH and elevated pleural glucose levels, PR presents with similar features to preexisting pleural effusion and that patients who develop PR faster tend to require intervention.

Anti-Mi-2 antibody-positive lung cancer-associated polymyositis.

After a 75-year-old man was diagnosed with lung cancer, proximal weakness and myalgia in the bilateral lower extremities developed, and the creatinine kinase (CK) level was elevated. The anti-Mi-2 antibody test was positive, muscle T2-weighted/fat-suppressed magnetic resonance imaging showed high intensity, and there were no skin lesions. Therefore, he was diagnosed with lung cancer-associated polymyositis (PM). The lung tumour shrank after chemotherapy, accompanied by gradual improvement of his PM-derived symptoms and CK level. Although positive anti-Mi-2 antibody tests rarely indicate PM and cancer, examining myositis-specific autoantibodies, including anti-Mi-2, should be considered if the CK level increases after a cancer diagnosis.