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Background: Acute exacerbation (AEx) of interstitial pneumonia is the most common lethal adverse event related to the pharmacological treatment of patients with lung cancer complicated with interstitial pneumonia. Although small cell lung cancer (SCLC) is linked to poor prognosis, it exhibits good response to chemotherapy. Few previous research studies have investigated the safety and efficacy of treatment for advanced SCLC complicated with idiopathic interstitial pneumonia (IIP). We conducted a single-arm phase II study to evaluate the safety and efficacy of carboplatin plus etoposide for the treatment of patients with SCLC complicated with IIP. Methods: Chemotherapy-naïve patients with advanced SCLC complicated with IIP were enrolled. Patients received carboplatin every 21–28 days at a dose of area under the curve 4–6 on day 1 and etoposide at a dose of 80–100 mg/m2 on days 1–3. Results: Thirty-one patients were enrolled between December 2009 and December 2022. A median of four cycles of carboplatin plus etoposide were administered. Acute exacerbation of idiopathic interstitial pneumonia was not observed; the rate of AEx was 0% (95% confidence interval [CI]: 0–9.6%, p = 0.038). The objective response rate was 83.9% (95% CI: 82.5–85.2). The median progression-free survival and overall survival were 5.9 (95% CI: 4.7–6.8) months and 14.0 (95% CI: 7.6–27.6) months, respectively. The 1-year survival rate was 61% (95% CI 41–76). Conclusions: The carboplatin plus etoposide treatment was tolerable and effective in SCLC patients complicated with IIP. [ABSTRACT FROM AUTHOR]

Osimertinib induces a marked response in non–small‐cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) gene mutations. However, acquired resistance to osimertinib remains an inevitable problem. In this study, we aimed to investigate osimertinib‐resistant mechanisms and evaluate the combination therapy of afatinib and chemotherapy. We established osimertinib‐resistant cell lines (PC‐9‐OR and H1975‐OR) from EGFR‐mutant lung adenocarcinoma cell lines PC‐9 and H1975 by high exposure and stepwise method. Combination therapy of afatinib plus carboplatin (CBDCA) and pemetrexed (PEM) was effective in both parental and osimertinib‐resistant cells. We found that expression of thrombospondin‐1 (TSP‐1) was upregulated in resistant cells using cDNA microarray analysis. We demonstrated that TSP‐1 increases the expression of matrix metalloproteinases through integrin signaling and promotes tumor invasion in both PC‐9‐OR and H1975‐OR, and that epithelial‐to‐mesenchymal transition (EMT) was involved in H1975‐OR. Afatinib plus CBDCA and PEM reversed TSP‐1‐induced invasion ability and EMT changes in resistant cells. In PC‐9‐OR xenograft mouse models (five female Balb/c‐Nude mice in each group), combination therapy strongly inhibited tumor growth compared with afatinib monotherapy (5 mg/kg, orally, five times per week) or CBDCA (75 mg/kg, intraperitoneally, one time per week) + PEM (100 mg/kg, intraperitoneally, one time per week) over a 28‐day period. These results suggest that the combination of afatinib plus CBDCA and PEM, which effectively suppresses TSP‐1 expression, may be a promising option in EGFR‐mutated NSCLC patients after the acquisition of osimertinib resistance. [ABSTRACT FROM AUTHOR]

Chronic constipation is a common gastrointestinal disorder, and its management is critical. However, it is extremely difficult to assess its subjective symptoms when patients are unable to report them due to cognitive or physical disabilities, especially in cases of patients with incurable geriatric, pediatric, palliative, psychiatric, or neurological diseases. We had previously established a protocol for observing and assessing rectal fecal retention using ultrasonography and for classifying cases into three categories based on the rectal findings: no fecal retention, fecal retention without hard stools, and fecal retention with hard stools. However, although the detection of rectal fecal retention using ultrasonography would be expected to lead to better therapeutic management, there is no standard algorithm for selecting specific treatments and defecation care options based on ultrasonographic findings. Therefore, we organized an expert consensus meeting of multidisciplinary professionals to develop such an algorithm based on rectal ultrasonography findings for patients with constipation in both residential and hospital settings. [ABSTRACT FROM AUTHOR]

Background: Transabdominal ultrasound is used to detect fecal impaction, but the rectum is difficult to visualize without bladder urine or with gastrointestinal gas. Objective: We developed a transgluteal cleft approach that is unaffected by these factors and sought to determine if our ultrasound method could detect and classify fecal matter in the lower rectum using this approach. Methods: We classified ultrasound images from hospitalized patients into four groups: Group 1 (bowed and rock-like echogenic areas), Group 2 (irregular and cotton candy-like hyperechoic areas), Group 3 (flat and mousse-like hyperechoic areas), and Group 4 (linear echogenic areas in the lumen). Stool characteristics were classified as hard, normal, and muddy/watery. Sensitivity and specificity were determined based on fecal impaction and stool classification accuracy. Results: We obtained 129 ultrasound images of 23 patients. The sensitivity and specificity for fecal retention in the rectum were both 100.0%. The recall rates were 71.8% for Group 1, 93.1% for Group 2, 100.0% for Group 3, and 100.0% for Group 4. The precision rates were 96.6% for Group 1, 71.1% for Group 2, 88.9% for Group 3, and 100.0% for Group 4. Our method was 89.9% accurate overall. Conclusion: Transgluteal cleft approach ultrasound scanning can detect and classify fecal properties with high accuracy. [ABSTRACT FROM AUTHOR]

Introduction: A neurotrophic tropomyosin receptor kinase (NTRK)‐tyrosine kinase inhibitor (TKI) has shown dramatic efficacy against malignant tumors harboring an NTRK fusion gene. However, almost all tumors eventually acquire resistance to NTRK‐TKIs. Method: To investigate the mechanism of resistance to NTRK‐TKIs, we established cells resistant to three types of NTRK‐TKIs (larotrectinib, entrectinib, and selitrectinib) using KM12 colon cancer cells with a TPM3‐NTRK1 rearrangement. Result: Overexpression of 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2 (HMGCS2) was observed in three resistant cells (KM12‐LR, KM12‐ER, and KM12‐SR) by microarray analysis. Lower expression of sterol regulatory element‐binding protein 2 (SREBP2) and peroxisome proliferator activated receptor α (PPARα) was found in two cells (KM12‐ER and KM12‐SR) in which HMGCS2 was overexpressed compared to the parental KM12 and KM12‐LR cells. In resistant cells, knockdown of HMGCS2 using small interfering RNA improved the sensitivity to NTRK‐TKI. Further treatment with mevalonolactone after HMGCS2 knockdown reintroduced the NTRK‐TKI resistance. In addition, simvastatin and silibinin had a synergistic effect with NTRK‐TKIs in resistant cells, and delayed tolerance was observed after sustained exposure to clinical concentrations of NTRK‐TKI and simvastatin in KM12 cells. In xenograft mouse models, combination treatment with entrectinib and simvastatin reduced resistant tumor growth compared with entrectinib alone. Conclusion: These results suggest that HMGCS2 overexpression induces resistance to NTRK‐TKIs via the mevalonate pathway in colon cancer cells. Statin inhibition of the mevalonate pathway may be useful for overcoming this mechanistic resistance. [ABSTRACT FROM AUTHOR]

Background: The epidermal growth factor receptor (EGFR) mutation is a risk factor associated with brain metastases (BMs) in patients with non‐small cell lung cancer (NSCLC). This study aimed to evaluate the impact of osimertinib early dose reduction on BM worsening. Methods: We retrospectively analyzed EGFR‐mutant NSCLC patients treated with osimertinib as first‐line treatment between August 2018 and October 2021. To evaluate the impact of osimertinib early dose reduction, we performed a landmark analysis of patients who achieved disease control at 4 months. Patients were divided into two groups according to whether the osimertinib dose was reduced or not, within 4 months after the start of treatment. We evaluated the time to BMs onset or progression, progression‐free survival, and overall survival. Results: In total, 62 NSCLC patients with EGFR mutations were analyzed. Thirteen patients experienced early dose reduction of osimertinib treatment. Seven patients received osimertinib 40 mg daily, and six received 80 mg every other day. The most common reason for dose reduction was gastrointestinal toxicity (n = 4), followed by skin rashes (n = 3). The time to BMs onset or progression was significantly shorter in patients who experienced early dose reduction than in those who continued regular treatment (Hazard ratio 4.47, 95% confidence interval, 1.52–13.11). The 1‐year cumulative incidence of BM onset or progression was 23.1% in the reduced‐dose group and 5.0% in the standard dose group. The risk of worsening BMs with early dose reduction of osimertinib treatment was higher in patients who had BMs before treatment and in younger patients. Conclusion: Early dose reduction of osimertinib was a risk factor for the worsening of BMs. A higher risk was associated with younger patients and those presenting BMs before treatment. [ABSTRACT FROM AUTHOR]

Background: Nab‐paclitaxel (nab‐PTX) has better transfer to tumor tissue than cremophor‐based paclitaxel. It suggests that the optimum dose of nab‐PTX might be lower than the dose and schedule that is widely used. We designed a randomized phase II trial to examine the clinical utility and safety of nab‐PTX in patients with previously treated advanced non‐small cell lung cancer (NSCLC). Methods: Patients were randomly allocated (1:1) to receive nab‐PTX monotherapy at 100 mg/m2 (group A) or 70 mg/m2 (group B). The primary endpoint was progression‐free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results: Finally, 81 patients were randomized. Similar results were observed in both groups for PFS (3.75 vs. 3.71 months), OS (13.50 vs. 16.13 months), or ORR (20.5% vs. 23.1%). The incidences of grade 3 or worse AEs were 57.5% in group A and 41.5% in group B. The proportion of serious side effects was 10.0% in group A and 4.9% in group B. Conclusion: Both standard dose and low dose of nab‐PTX monotherapy are active for previously treated NSCLC patients with better safety profile. Therefore, nab‐PTX 70 mg/m2 dose and schedule in the trial would be a reasonable option. [ABSTRACT FROM AUTHOR]

Propolis is a resinous substance collected by honeybees from various plant sources and has been used in traditional folk medicine for centuries. Propolis has various biological properties, including antibacterial, antiviral, anti-inflammatory, and anti-tumor properties. The use of propolis in oral health care is attributable to its antimicrobial and anti-inflammatory effects. However, limited evidence exists on the in vivo efficacy of propolis against periodontal pathogens. We aimed to evaluate the efficacy of Brazilian green propolis (BGP)-containing toothpaste for improving the oral environment and define its antibacterial compounds. Overall, 48 student volunteers aged 18–40 years (24 females and 24 males) were randomly categorized into the BGP and placebo groups. The BGP and placebo groups received toothpaste with and without BGP, respectively. After a baseline assessment, the plaque index (PI) score, gingival index (GI) score, and proportion of periodontal pathogens on the tongue surface were analyzed at 0, 1, and 2 weeks. Antibacterial compounds were identified using liquid-liquid partitioning, high-performance liquid chromatography purification, and nuclear magnetic resonance methods. The concentration of BGP in the toothpaste was set at 0.0347 w/v%. Compared with the placebo group, the BGP group demonstrated a reduction in the PI score (p < 0.05) but not in the GI score, as well as a reduction in Porphyromonas gingivalis (Pg)/Total bacteria (Tb), Fusobacterium nucleatum (Fn)/Tb, and Aggregatibacter actinomycetemcomitans (Aa)/Tb (p < 0.05) but not in Streptococcus salivalius /Tb. Effect sizes for Pg , Fn and Aa were 0.360, 0.556, and 0.164, respectively. The antibacterial compounds of the BGP-containing toothpaste included a mixture of kaempferide/betuletol. We confirmed the efficacy of propolis toothpaste with an optimal kaempferide/betuletol ratio for improving oral microbiota, thereby suggesting that BGP toothpaste is clinically useful in maintaining oral health and preventing periodontal disease. [Display omitted] [ABSTRACT FROM AUTHOR]