Assessment of anti-PD-(L)1 for patients with coexisting malignant tumor and tuberculosis classified by active, latent, and obsolete stage.

BACKGROUND: It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown. METHODS: This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated. RESULTS: A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01-11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy. CONCLUSIONS: This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.

The prognostic role of age in primary cutaneous B-cell lymphoma: a proposal derived from a population-based registry.

PURPOSE: A few prognostic predicting systems existed for primary cutaneous B-cell lymphoma (PCBCL). However, none of them took age into consideration. We sought to declare the prognostic role of age in PCBCL. MATERIALS AND METHODS: A total of 4859 patients were identified in the surveillance, epidemiology and end results data, spanning 1975-2016. The association between age and survival was determined using unadjusted and adjusted proportional hazard analysis. RESULTS: There was a uni-modal distribution of age, with most in the seventh decade (22%), followed by the sixth and eighth decades (19%). As a continuous variable, age was demonstrated to have an adverse effect on overall survival (OS, HR, 1.077, 95% CI 1.073-1.082, p = 0.000) and cancer-specific survival (CSS, HR, 1.099, 95% CI 1.092-1.106, p = 0.000) after adjusted proportional hazard analysis. Patients aged ≤ 60 years had significantly higher survival rates than those aged > 60 (5-year OS was 93% vs 64%, 10-year OS was 90% vs 45%, p = 0.000; 5-year CSS was 98% vs 80%, 10-year CSS 96% was 62%, p = 0.000). Similar survival trends were also observed in different sub-group analyses, including disease with different stages (p = 0.000), different histology subgroups (p = 0.000), and different sites (p = 0.000). CONCLUSION: Age has an important effect on overall survival and cancer-specific survival. The addition of age to the primary site, histology, and stage improves predicting long-term outcomes in cutaneous B-cell lymphoma.

Deletion of bem46 retards spore germination and may be related to the polar growth of Aspergillus fumigatus.

Bud emergence 46 (BEM46), a member of the α/ß hydrolase superfamily, has been reported to be essential for polarized growth in Neurospora crassa. However, the role of BEM46 in aspergillus fumigatus (A. fumigatus) remains unclear. In this study, we constructed an A. fumigatus strain expressing BEM46 fused with enhanced green fluorescent protein, and a Δbem46 mutant, to explore the localization and the role of growth of BEM46 in A. fumigatus, respectively. Confocal laser scanning microscopy revealed that BEM46 was dominantly expressed in the sites where hyphae germinated from conidia in A. fumigatus. When compared with the control strain, the Δbem46 mutant exhibited insignificant morphological changes but delayed germination. No significant changes were found regarding the radial growth of both strains in response to various antifungal agents. These results suggest that BEM46 plays an essential role in timely germination in A. fumigatus. From the observation of fluorescence localization, we infer that that BEM46 might be involved in polarized growth in A. fumigatus.

Unconventional implant strategy for patients with a limited interocclusal space in the posterior region: a case report.

BACKGROUND: Implant prostheses require sufficient interocclusal space. In cases of limited interocclusal space, reducing or extracting over-erupted opposing teeth, orthodontic intrusion, or surgical reconstruction of the edentulous space are commonly used to restore the interocclusal space. However, there are disadvantages to these approaches. CASE PRESENTATION: The present case report describes a patient with a limited interocclusal space managed using an unconventional implant strategy. CONCLUSIONS: The patient presented satisfactory outcomes without any signs of implant failure, suggesting that the unconventional implant treatment strategy is a useful option for patients with a limited interocclusal space in the posterior region. This unconventional implant surgery provides a minimally invasive treatment alternative.

The Prognostic Value of Alpha-Fetoprotein Ratio in Patients With Resectable Alpha-Fetoprotein-Negative Hepatocellular Carcinoma.

PURPOSE: This study aimed to investigate the prognostic value of alpha-fetoprotein (AFP) ratio in patients with AFP-negative hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We retrospectively analyzed 600 AFP-negative HCC patients who underwent hepatectomy. The AFP ratio was calculated as the ratio of AFP level 1 week before surgery to the level 20-40 days after hepatectomy. Immunohistochemistry assay was used to assess protein expression in HCC tissue. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS: The study found that a cutoff value of 1.6 ng/ml for AFP ratio, determined using X-tile software, was optimal for predicting prognosis. Patients with a high AFP ratio had a worse prognosis compare to those with a low AFP ratio (DFS, P = .026; OS, P = .034). Patients with a high AFP ratio had a worse prognosis compared to those with a low AFP ratio. Multivariate analysis revealed that AFP ratio >1.6, negative HepPar-1 expression, and vascular invasion were independent predictors of both DFS and OS. Vascular invasion had a higher area under the curve (AUC) than AFP ratio and HepPar-1 expression in predicting recurrence and death. The combination of AFP ratio, HepPar-1 expression, and vascular invasion provided better predictive accuracy for DFS and OS. CONCLUSION: The AFP ratio is a potential prognostic marker for AFP-negative HCC patients after hepatectomy. Combining the analysis of AFP ratio with HepPar-1 expression and vascular invasion can enhance the accuracy of predicting prognosis in these patients.

Association of KLK4 rs2235091 polymorphism with susceptibility to dental caries: a systematic review and meta-analysis.

Objective: To investigate the association between Kallikrein-related peptidase-4 (KLK4) rs2235091 polymorphism and susceptibility to dental caries (DC) by a method of systematic review and meta-analysis. Methods: Four English databases were searched for studies on the correlation between KLK4 rs2235091 polymorphism and susceptibility to DC from inception to April 1, 2023. Data analysis was processed by Stata 15.0 software. Results: Four articles were eligible, including 848 individuals with caries and 463 controls. The results of pooled analysis showed no significant differences in the five gene models (G vs. A: odds ratio (OR) = 1.14, 95% CI: 0.73-1.79, P = 0.567; GG + GA vs. AA: OR = 1.01, 95% CI: 0.77-1.32, P = 0.489; GG vs. GA + AA: OR = 0.84, 95% CI: 0.57-1.23, P = 0.368; GA vs. AA: OR = 1.06, 95% CI: 0.80-1.41, P = 0.681; GG vs. AA: OR = 1.15, 95% CI: 0.57-2.31, P = 0.690). However, subgroup analysis indicated a statistically significant difference in the dominant (GG + GA vs. AA: OR = 1.74, 95% CI: 1.02-2.96, P = 0.042) gene model in primary dentition, but no significance in allelic, recessive, homozygous and heterozygous models. Besides, in permanent dentition, no significant differences were found among the five genetic models (all P > 0.05). Conclusion: KLK4 rs2235091 polymorphism may be associated with susceptibility to DC of pediatric primary dentition, but not with the risk of caries of permanent dentition. Genotype GG + GA may increase susceptibility to DC of pediatric primary dentition. However, considering the limited records enrolled in this review, more trials with larger sample sizes and more rigorous designs are needed to verify the conclusions of this meta-analysis in the future. Systematic Review Registration: https://inplasy.com/, identifier INPLASY202380014.

A Model Based on Artificial Intelligence Algorithm for Monitoring Recurrence of HCC after Hepatectomy.

BACKGROUND: There is no satisfactory indicator for monitoring recurrence after resection of hepatocellular carcinoma (HCC). This retrospective study aimed to design and validate an HCC monitor recurrence (HMR) model for patients without metastasis after hepatectomy. METHODS: A training cohort was recruited from 1179 patients with HCC without metastasis after hepatectomy between February 2012 and December 2015. An HMR model was developed using an AdaBoost classifier algorithm. The factors included patient age, TNM staging, tumor size, and pre/postoperative dynamic variations of alpha-fetoprotein (AFP). The diagnostic efficacy of the model was evaluated based on the area under the receiver operating characteristic curves (AUCs). The model was validated using a cohort of 695 patients. RESULTS: In preoperative patients with positive or negative AFP, the AUC of the validation cohort in the HMR model was .8877, which indicated better diagnostic efficacy than that of serum AFP (AUC, .7348). The HMR model predicted recurrence earlier than computed tomography/magnetic resonance imaging did by 191.58 ± 165 days. In addition, the HMR model can predict the prognosis of patients with HCC after resection. CONCLUSIONS: The HMR model established in this study is more accurate than serum AFP for monitoring recurrence after hepatectomy for HCC and can be used for real-time monitoring of the postoperative status in patients with HCC without metastasis.

Assessment of the Clinical Diagnosis of Onychomycosis by Dermoscopy.

Background: As a common clinical superficial fungal infection, the diagnosis of onychomycosis relies on clinical features, traditional KOH direct microscopy and fungal culture. In recent years, dermoscopy has been widely used in the diagnosis and treatment of infectious diseases and has provided new options for the diagnosis of onychomycosis. Objective: To evaluate the value of dermoscopy in the clinical diagnosis of onychomycosis and to explore the relationship between each clinical subtype and the dermoscopic pattern. Methods: A retrospective study of 114 cases of clinically suspected onychomycosis was conducted to compare the differences between dermoscopy and fungal pathogenic examination (microscopy and culture) in the diagnostic sensitivity of onychomycosis and to analyze the relationship between nine common dermoscopic modalities and clinical subtypes of onychomycosis. Results: Among the 114 proposed patients, 87 nails with positive fluorescent staining microscopy and/or positive fungal cultures were diagnosed as onychomycosis. The sensitivity and specificity of dermatoscopy, using the mycological findings as a reference, were 86.21 and 33.33%, respectively. The incidence of common dermatoscopic patterns in the 87 nails with confirmed onychomycosis was as follows: white flocculation in 76 cases (87.35%), longitudinal nail pattern in 72 cases (82.76%), jagged changes in the distal nail plate in 69 cases (79.31%) and yellow staining in 46 cases (52.87%), these four patterns were more commonly seen in the distal lateral subungual onychomycosis and total dystrophic onychomycosis, but there was no statistical difference in the positive dermatoscopic pattern between these two types (P > 0.05). Conclusion: Dermoscopy can be an important aid in the diagnosis of onychomycosis, especially when fungal microscopy or culture is not appropriate, but this method is still not a substitute for fungal microscopy and culture.

Alpha-Fetoprotein Ratio Predicts Alpha-Fetoprotein Positive Hepatocellular Cancer Patient Prognosis after Hepatectomy.

BACKGROUND: This study was conducted to investigate the effect of alpha-fetoprotein (AFP) ratio on the prognosis of AFP-positive hepatocellular carcinoma (HCC) patients after hepatectomy. METHODS: We retrospectively included 879 HCC patients with AFP-positive who underwent hepatectomy from February 2012 to October 2017 and randomly divided into training cohort and validation cohort. AFP ratio was equal to the AFP level within one week before hepatectomy to AFP level within 20-40 days after surgery. The end point of follow-up was disease-free survival (DFS) and overall survival (OS). RESULTS: AFP ratio was not associated with clinical characteristics in training cohort and validation cohort. According to the X-tile software, the optimum cut-off point was 17.8 for AFP ratio. Significant differences between AFP ratio high and AFP ratio low were observed in DFS and OS in both cohort (p < 0.05). Kaplan-Meier curves and receiver-operating curves were showed that AFP ratio was better than AFP level preoperation in predicting the prognosis of AFP-positive HCC patients after hepatectomy. The multivariate analysis demonstrated that AFP ratio was a significant independent risk factor for both OS and DFS in HCC patients with AFP-positive. CONCLUSIONS: AFP ratio might be a prognosis predictor for HCC patients with AFP-positive after hepatectomy.

Smoking status combined with tumor mutational burden as a prognosis predictor for combination immune checkpoint inhibitor therapy in non-small cell lung cancer.

BACKGROUND: This study aimed to explore the prognostic value of tumor mutational burden (TMB) combined with smoking status in advanced non-small cell lung cancer (NSCLC) patients who received immune checkpoint inhibitor therapy (anti PD-1/PD-L1 therapy) combined with chemotherapy or anti-angiogenesis therapy. METHODS: We conducted a retrospective analysis of NSCLC patients who underwent next-generation sequencing test (either 295-gene panel NGS or 1021-gene panel NGS) from September 2017 to November 2020. The relationship between TMB and smoking status was investigated. Kaplan-Meier survival analysis was used to compare progression-free survival (PFS) of the NSCLC patients who received combination immunotherapy grouped by TMB value and smoking status. RESULTS: We enrolled 323 cases and 388 cases of NSCLC patients in the 295-gene panel cohort and 1021-gene panel cohort, respectively. Positive correlation between TMB and smoking status was found in lung adenocarcinoma, but not in lung squamous cell carcinoma. Participants with both high TMB and smoking status who received immune checkpoint therapy combined with chemotherapy or anti-angiogenesis therapy had longer PFS than other participants (p < 0.05). CONCLUSIONS: The combination of TMB with smoking status might be a potential predictor for the efficacy of combination immunotherapy in advanced NSCLC.

Efficacy and safety of concurrent anti-tuberculosis treatment and chemotherapy in lung cancer patients with co-existent tuberculosis.

BACKGROUND: This retrospective study evaluated the safety and efficacy of concurrent anti-tuberculosis (TB) and chemotherapy treatment in patients with advanced lung cancer and active TB. METHODS: We retrospectively analyzed patients who were first diagnosed with advanced lung cancer and received first-line chemotherapy in Guangzhou Chest Hospital from 2015 to 2017. Patients were categorized into two groups (2:1): lung cancer patients without active TB (Group A), and lung cancer patients with active TB (Group B). Primary endpoints included adverse events (AEs), objective response rate (ORR), time to treatment failure, and overall survival (OS). RESULTS: A total of 99 patients were eligible (Group A, n=66; Group B, n=33). Grade ≥3 treatment-related AEs, primarily hematologic toxicity, occurred in 39.4% and 51.5% of patients in Groups A and B, respectively. The hypohepatia in both groups was generally at grade 1 or 2, with similar incidences (26% and 27%, respectively). After two cycles of chemotherapy, the ORR was 42.4% and 33.3% in Group A and B, respectively (P=0.383). The median time to treatment failure (TTF) was 7.0 and 5.6 months for Groups A and B, respectively (P=0.175). The median OS was 17.0 and 14.0 months for Groups A and B, respectively (P=0.312). After 3 months of anti-TB treatment, all patients achieved sputum acid-fast bacilli (AFB) smear conversion and absorption on imaging, and the end of follow-up observed no recurrence. CONCLUSIONS: Concurrent anti-TB and chemotherapy treatment did not increase hematological toxicity or hypohepatia in lung cancer patients with pulmonary TB.

Interfering Expression of Chimeric Transcript SEPT7P2-PSPH Promotes Cell Proliferation in Patients with Nasopharyngeal Carcinoma.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer which is mostly prevalent in southern China. The development of NPC involves accumulation of multiple genetic changes. Chromosomal translocation is always thought to be accompanied with the fusion chimeric products. To data, the role of the fusion chimeric transcript remains obscure. MATERIALS AND METHODS: We performed RNA sequencing to detect the fusion genes in ten NPC tissues. Sanger sequencing and quantitative RT-PCR were used to measure the level of the fusion chimeric transcript in NPC tissues and cell lines. The functional experiments such as CCK8 assay, colony formation, and migration/invasion were conducted to analyze the role of this transcript in NPC in vitro. RESULTS: We demonstrated that the chimeric transcript SEPT7P2-PSPH was formed by trans-splicing of adjacent genes in the absence of chromosomal rearrangement and observed in both NPC patients and cell lines in parallel. Low-expression of the SEPT7P2-PSPH chimeric transcript induced the protein expression of PSPH and promoted cell proliferation, metastasis/invasion, and transforming ability in vitro. CONCLUSIONS: Our findings indicate that the chimeric transcript SEPT7P2-PSPH is a product of trans-splicing of two adjacent genes and might be a tumor suppressor gene, potentially having the role of anticancer activity.

Tumor Mutational Burden and Genomic Alterations in Chinese Small Cell Lung Cancer Measured by Whole-Exome Sequencing.

PURPOSE: Studies on genetic alterations of the heterogenous small cell lung cancer (SCLC) are rare. We carried out the present study to clarify the genomic alterations and TMB levels of Chinese SCLC patients by whole-exome sequencing. MATERIALS AND METHODS: Whole-exome sequencing by next-generation sequencing technique was implemented on twenty SCLC samples. Significant somatic mutations and copy number variations were screened, followed by comparison with the data extracted from COSMIC. Besides, altered signaling pathways were examined in order to figure out actionable targets. RESULTS: A total of 8,062 nonsynonymous mutations were defined. The number of mutations for each case ranged from 98 to 864. As for base substitutions, a total of 15,817 substitutions were detected with C > A conversion which was correlated to smoking occupying 25.57%. The TMB values ranged from 2.51/Mb to 22.1/Mb with a median value of 9.95/Mb. RB1 was the most frequently mutated gene altered in 18 (90%) cases, followed by TP53 altered in 17 (85%) cases. Other commonly changed genes were PTEN, and RBL1, with frequencies of 55% and 50%, respectively. SOX2 significantly amplified in 6 (30%) cases and MYCN amplified in 1 (5%) patient. Notch signaling pathway and PI3K/AKT/mTOR signaling pathway were universally and significantly changed. Major genomic alterations were in consistency with data from COSMIC, but frequencies of less common mutations were different. CONCLUSION: TP53 and RB1 inactivations were universally detected in SCLC. The Notch and PI3K/AKT/mTOR signaling pathways were both significantly altered, implying potential actionable targets.

Research of Mrr1, Cap1 and MDR1 in Candida albicans resistant to azole medications.

The aim of the present study was to investigate the association between Mrr1, adenylyl cyclase-associated protein 1 (Cap1) and multi-drug resistance gene 1 (MDR1), and to assess the mutations in Mrr1 and Cap1 in azole-resistant Candida albicans strains. The study isolated 68 C. albicans strains from patients with vulvovaginal candidiasis. Drug susceptibility testing was conducted to characterize the resistance profile of these strains to fluconazole, itraconazole and voriconazole. Polymerase chain reaction (PCR) amplification was performed for Cap1 and Mrr1, and the PCR products were sequenced to identify any mutations. Reverse transcription-quantitative PCR was performed to measure Cap1, Mrr1 and MDR1 mRNA in C. albicans strains. The results of the present study indicated S381N, P311S and A390T missense mutations in Cap1 and T917M, T923I, N937K, E1020Q, F1032L and S1037L missense mutations in Mrr1 in azole-resistant C. albicans strains. Fluconazole-resistant strains had significantly elevated Cap1 and MDR1 mRNA levels compared with fluconazole-sensitive strains (P<0.01). The mRNA levels of Cap1, Mrr1 and MDR1 were significantly increased in the strains resistant to all three of fluconazole, itraconazole and voriconazole compared with strains sensitive to the three agents (P<0.001, P=0.037 and P<0.001, respectively). Cap1 expression was positively correlated with MDR1 expression in fluconazole-resistant strains (P<0.05). No significant correlation was observed between Cap1, Mrr1 and MDR1 in the strains resistant to fluconazole, itraconazole or voriconazole. The results of the present study suggested that fluconazole resistance may involve MDR1 overexpression mediated by Cap1 overexpression. Cross-resistance between fluconazole, itraconazole and voriconazole may be associated with mutations in Cap1 and Mrr1, rather than their overexpression. In addition, the present study also revealed two novel mutations in Mrr1; T917M and T923I. These findings may provide a basis for elucidating the molecular mechanisms of and improving therapeutic treatments to tackle azole resistance.

Mutations and/or Overexpressions of ERG4 and ERG11 Genes in Clinical Azoles-Resistant Isolates of Candida albicans.

OBJECTIVE: We aimed to investigate whether mutations and/or overexpressions of ERG4 and ERG11 genes were involved in drug resistance to azoles in Candida albicans. METHODS: Totally, 34 clinical isolates of C. albicans were included in this study. Antimicrobial susceptibility tests, including 5-fluorocytosine (5-FC), amphotericin B (AMB), fluconazole (FCA), itraconazole (ITR), and voriconazole (VRC), were performed by broth microdilution method. Mutations in the ERG4 and ERG11 genes sequence were detected. The messenger RNA (mRNA) levels of ERG4 and ERG11 were measured by quantitative real-time polymerase chain reaction. The correlation of the expression levels of ERG4 with ERG11 genes in susceptible isolates and resistant isolates was analyzed by Pearson's correlation analysis. RESULTS: Among 34 C. albicans isolates, 52.94%, 70.59%, and 50.00% isolates were resistant to FCA, ITR, and VRC, respectively. Sequencing results revealed that only 2 silent mutations were found in ERG4 gene, while 10 amino acid substitutions, including 6 reported previously and 4 new identified, were frequently found in ERG11 gene. The mRNA levels of ERG4 and ERG11 genes were significantly elevated in resistant compared with susceptible C. albicans isolates. Furthermore, the mRNA level of ERG4 was positively correlated with ERG11 in susceptible but not resistant C. albicans isolates. CONCLUSIONS: The resistance to azoles may be associated with the mutations in ERG11 but not ERG4 gene in C. albicans isolates. In addition, overexpressed ERG4 and ERG11 genes are found in resistant C. albicans isolates, and the mRNA levels of ERG4 may be irrelevant to ERG11 in resistant C. albicans isolates.

The Frequency and Clinical Implication of ROS1 and RET Rearrangements in Resected Stage IIIA-N2 Non-Small Cell Lung Cancer Patients.

To evaluate the frequency and clinicopathological features of ROS1 and RET rearrangements in N2 node positive stage IIIA (IIIA-N2) non-small cell lung cancer (NSCLC) patients, we retrospectively screened 204 cases with a tissue microarray (TMA) panel by fluorescent in situ hybridization (FISH), and confirmed by direct sequencing and immunohistochemistry (IHC). The relationship between ROS1 or RET rearrangements, clinicopathological features, and prognostic factors were analyzed in resected stage IIIA-N2 NSCLC. Of the 204 cases, 4 cases were confirmed with ROS1 rearrangement, but no RET rearrangement was detected. All 4 ROS1-rearranged cases were adenocarcinomas. The predominant pathological type was acinar pattern in ROS1-rearranged tumors, except for 1 case harboring a mixture acinar and mucous tumor cells. Variants of ROS1 rearrangement were SDC4-ROS1 (E2:E32), SDC4-ROS1 (E4:E32) and SDC4-ROS1 (E4:E34). There was no significant association between ROS1 rearrangement and clinicopathological characteristics. In this cohort, multivariate analysis for overall survival (OS) indicated that squamous cell carcinoma and lobectomy were independent predictors of poor prognosis; R0 surgical resection and non-pleural invasion were independent predictors of good prognosis. In resected stage IIIA-N2 NSCLC patients, ROS1-rearranged cases tended to occur in younger patients with adenocarcinomas. The prognosis of resected stage IIIA-N2 is generally considered poor, but patients with ROS1 rearrangement will benefit from the targeted therapy.

Clinical presentation of a patient with congenital cutis laxa and abnormal thyroid hormone levels.

We describe a case of generalized cutis laxa (CL) in a 7-year-old female child. At 2 months of age, she was found to have a hoarse voice, and at 3 years, she was much smaller than her peers. Her aging face and short stature caught our attention, and the treatment of the patient was accepted by our hospital. She underwent a thorough examination. X-ray of the wrist bone showed a markedly delayed bone age, and thyroid function tests revealed significantly elevated free triiodothyronine 3 and free thyroxine 4 levels, but thyrotropin was within the normal range. Thyroid dysfunction and CL can be associated with lagged growth and development. Whether her abnormal development was due to thyroid dysfunction or CL could not be ascertained. CL is possibly more complex than it has been supposed so far, and is therefore worth to be further studied.