Prevention and management of cytomegalovirus infection and disease in kidney transplant: A consensus statement of the Transplantation Society of Taiwan.

Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care.

Oral administration of Lactobacillus delbrueckii subsp. lactis LDL557 attenuates airway inflammation and changes the gut microbiota in a Der p-sensitized mouse model of allergic asthma.

BACKGROUND: Lactic acid bacteria may be used as probiotics to prevent or treat various diseases, and Lactobacillus delbrueckii has an inhibitory effect on the development of atopic diseases. OBJECTIVE: This study explored the effects of L. delbrueckii subsp. lactis strain LDL557 administration on a mouse asthma model resulting from Dermatophoides pteronyssinus (Der p) sensitization and investigated the associated gut microbiota. METHODS: Der p-sensitized and challenged BALB/c mice were orally administered with three different doses of live (low, 107 colony-forming units (CFU); medium, 108 CFU; high, 109 CFU) and heat-killed (109 cells) LDL557 in 200 µL of PBS daily, starting 2 weeks before Der p sensitization and lasting 4 weeks. After the allergen challenge, airway responsiveness to methacholine and the influx of inflammatory cells to the lungs were assessed. The gut microbiome was obtained by sequencing the V3-V4 region of the 16S rRNA gene from mice stool samples. RESULTS: LDL557 in the live (109 CFU) and heat-killed (109 cells) conditions reduced the airway hyper-responsiveness after stimulation with methacholine, inflammatory cell infiltration, and mucus production. These effects were similar to those in groups treated with dexamethasone. No significant change in the gut microbiota was observed after LDL557 treatment, except for the tendency of heat-killed LDL557 to change the gut microbial profile to a greater extent than live LDL557. CONCLUSION: In summary, we found that live and heat-killed LDL557 had the beneficial effect of preventing Der p-induced allergic inflammation in a mouse model of asthma.

Cucurbitacin E Exerts Anti-Proliferative Activity via Promoting p62-Dependent Apoptosis in Human Non-Small-Cell Lung Cancer A549 Cells.

EGFR tyrosine kinase inhibitors (TKIs) are the first-line treatment for advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, NSCLC patients with wild-type EGFR and KRAS mutation are ineligible for EGFR-TKIs. Therefore, the discovery of new therapeutic agents is urgently needed for NSCLC patients who cannot receive targeted therapies. Natural products possess tremendous chemical diversity and have been extensively investigated for their anticancer activity. In this study, we found that Cucurbitacin E (Cu E), a triterpene of cucurbitacins widely presented in the edible plants of the Cucurbitaceae family, significantly inhibits the viability and proliferation of A549 cells that harbor wild-type EGFR and KRAS mutation. Our results revealed that Cu E increases cell-cycle arrest at G2/M and subG1 phase. Mechanistically, Cu E significantly inhibits the phosphorylation and protein levels of regulatory proteins and hinders G2/M cell-cycle progression. Meanwhile, the treatment of Cu E resulted in DNA damage response and apoptosis. For the first time, we observed that Cu E induces incomplete autophagy as evidenced by increased LC3B-II expression and p62-accumulation. Knockdown of p62 rescued the cells from Cu E-mediated anti-proliferative effect, apoptosis, DNA damage, and ROS production. These findings suggest that Cu E is a promising drug candidate for NSCLC.

Association between microcirculation in spontaneous breathing trial and extubation success.

PURPOSE: This study assessed the association between changes in sublingual microcirculation after a spontaneous breathing trial (SBT) and successful extubation. MATERIALS AND METHODS: Sublingual microcirculation was assessed using an incident dark-field video microscope before and after each SBT and before extubation. Microcirculatory parameters before the SBT, at the end of the SBT, and before extubation were compared between the successful and failed extubation groups. RESULTS: Forty-seven patients were enrolled and analysed in this study (34 patients in the successful extubation group and 13 patients in the failed extubation group). At the end of the SBT, the weaning parameters did not differ between the two groups. However, the total small vessel density (21.2 [20.4-23.7] versus 24.9 [22.6-26.5] mm/mm2), perfused small vessel density (20.6 [18.5-21.8] versus 23.1 [20.9-25] mm/mm2), proportion of perfused small vessels (91 [87-96] versus 95 [93-98] %), and microvascular flow index (2.8 [2.7-2.9] versus 2.9 [2.9-3]) were significantly lower in the failed extubation group than in the successful extubation group. The weaning and microcirculatory parameters did not differ significantly between the two groups before the SBT. CONCLUSIONS: More patients are required to investigate the difference between baseline microcirculation before a successful SBT and the change in microcirculation at the end of the SBT between the successful and failed extubation groups. Better sublingual microcirculatory parameters at the end of SBT and before extubation are associated with successful extubation.

Tumor necrosis factor-alpha blockade suppresses BK polyomavirus replication.

PURPOSE: BK Polyomavirus (BKPyV) infection manifests as renal inflammation and can cause kidney damage. Tumor necrosis factor-α (TNF-α) is increased in renal inflammation and injury. The aim of this study was to investigate the effect of TNF-α blockade on BKPyV infection. METHODS: Urine specimens from 22 patients with BKPyV-associated nephropathy (BKPyVN) and 35 non-BKPyVN kidney transplant recipients were analyzed. RESULTS: We demonstrated increased urinary levels of TNF-α and its receptors, TNFR1 and TNFR2, in BKPyVN patients. Treating BKPyV-infected human proximal tubular cells (HRPTECs) with TNF-α stimulated the expression of large T antigen and viral capsid protein-1 mRNA and proteins and BKPyV promoter activity. Knockdown of TNFR1 or TNFR2 expression caused a reduction in TNF-α-stimulated viral replication. NF-κB activation induced by overexpression of constitutively active IKK2 significantly increased viral replication and the activity of the BKPyV promoter containing an NF-κB binding site. The addition of a NF-κB inhibitor on BKPyV-infected cells suppressed viral replication. Blockade of TNF-α functionality by etanercept reduced BKPyV-stimulated expression of TNF-α, interleukin-1ß (IL-1ß), IL-6 and IL-8 and suppressed TNF-α-stimulated viral replication. In cultured HRPTECs and THP-1 cells, BKPyV infection led to increased expression of TNF-α, interleukin-1 ß (IL-1ß), IL-6 and TNFR1 and TNFR2 but the stimulated magnitude was far less than that induced by poly(I:C). This may suggest that BKPyV-mediated autocrine effect is not a major source of TNFα. CONCLUSION: TNF-α stimulates BKPyV replication and inhibition of its signal cascade or functionality attenuates its stimulatory effect. Our study provides a therapeutic anti-BKPyV target.

Performance of nonalcoholic fatty liver fibrosis score in estimating atherosclerotic cardiovascular disease risk.

BACKGROUND AND AIMS: It is currently unclear whether the nonalcoholic fatty liver disease (NAFLD) fibrosis score, when compared to major anthropometric indices, is useful in estimating the risk of atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: This study included 3886 adults undergoing a health checkup. An elevated risk of ASCVD was determined as a 10-year ASCVD risk ≥7.5% using Pooled Cohort Equations. NAFLD was diagnosed with abdominal ultrasonography. Receiver operating characteristic curves were used to evaluate the performance of estimating an elevated ASCVD risk. Among study participants, 521 (13.4%) had an elevated ASCVD risk and 1473 (37.9%) had NAFLD. Subjects with NAFLD had a significantly higher rate of ASCVD risk ≥7.5% (p < 0.001) compared to those without NAFLD. After adjusting for cardiometabolic risk factors, NAFLD (OR = 1.49, 95% CI: 1.10-2.00, p = 0.009) in all participants and NAFLD fibrosis score >0.676 (OR = 1.95, 95% CI: 1.30-2.92, p = 0.001) in individuals with NAFLD were significantly associated with an elevated risk of ASCVD. When compared to different anthropometric indices, NAFLD fibrosis score exhibited the largest area under the curve (AUC) in individuals with NAFLD (AUC = 0.750) in estimating an elevated ASCVD risk. Furthermore, NAFLD fibrosis score displayed the best predictive performance for identifying an elevated ASCVD risk in male participants with NAFLD (AUC = 0.737). CONCLUSION: NAFLD was a significant risk factor for elevated ASCVD risk. NAFLD fibrosis score >0.676 was associated with increased ASCVD risk in individuals with NAFLD. Compared with anthropometric indices, NAFLD fibrosis score demonstrated the best performance in estimating elevated ASCVD risk among those with NAFLD.

Total intravenous anesthesia decreases hospital stay but not incidence of postoperative pulmonary complications after lung resection surgery: a propensity score matching study.

BACKGROUND: There is no consensus regarding the superiority of volatile or total intravenous anesthesia (TIVA) in reducing the incidence of postoperative pulmonary complications (PPCs) after lung resection surgery (LRS). Thus, the aim of this study was to investigate the different anesthetic regimens and the incidence of PPCs in patients who underwent LRS. We hypothesized that TIVA is associated with a lower incidence of PPCs than volatile anesthesia. METHODS: This was a retrospective cohort study of patients who underwent LRS at Taipei Veterans General Hospital between January 2016 and December 2020. The patients' charts were reviewed and data on patient characteristics, perioperative features, and postoperative outcomes were extracted and analyzed. The patients were categorized into TIVA or volatile anesthesia groups and their clinical data were compared. Propensity score matching was performed to reduce potential selection bias. The primary outcome was the incidence of PPCs, whereas the secondary outcomes were the incidences of other postoperative events, such as length of hospital stay (LOS) and postoperative nausea and vomiting (PONV). RESULTS: A total of 392 patients each were included in the TIVA and volatile anesthesia groups. There was no statistically significant difference in the incidence of PPCs between the volatile anesthesia and TIVA groups. The TIVA group had a shorter LOS (p < 0.001) and a lower incidence of PONV than the volatile anesthesia group (4.6% in the TIVA group vs. 8.2% in the volatile anesthesia group; p = 0.041). However, there were no significant differences in reintubation, 30-day readmission, and re-operation rates between the two groups. CONCLUSIONS: There was no significant difference between the incidence of PPCs in patients who underwent LRS under TIVA and that in patients who underwent LRS under volatile anesthesia. However, TIVA had shorter LOS and lower incidence of PONV which may be a better choice for maintenance of anesthesia in patients undergoing LRS.

Prevention and management of tuberculosis in solid organ transplantation: A consensus statement of the transplantation society of Taiwan.

Solid organ transplant recipients have an increased risk of tuberculosis (TB). Due to the use of immunosuppressants, the incidence of TB among solid organ transplant recipients has been consistently reported to be higher than that among the general population. TB frequently develops within the first year after transplantation when a high level of immunosuppression is maintained. Extrapulmonary TB and disseminated TB account for a substantial proportion of TB among solid organ transplant recipients. Treatment of TB among recipients is complicated by the drug-drug interactions between anti-TB drugs and immunosuppressants. TB is associated with an increased risk of graft rejection, graft failure and mortality. Detection and management of latent TB infection among solid organ transplant candidates and recipients have been recommended. However, strategy to mitigate the risk of TB among solid organ transplant recipients has not yet been established in Taiwan. To address the challenges of TB among solid organ transplant recipients, a working group of the Transplantation Society of Taiwan was established. The working group searched literatures on TB among solid organ transplant recipients as well as guidelines and recommendations, and proposed interventions to strengthen TB prevention and care among solid organ transplant recipients.

NLRP3 Inflammasome Activates Endothelial-to-Mesenchymal Transition via Focal Adhesion Kinase Pathway in Bleomycin-Induced Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis has poor clinical outcomes despite antifibrotic treatment. The nucleotide-binding domain leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3) inflammasome and endothelial-to-mesenchymal transition (EndoMT) were shown to be involved in the pathogenesis of pulmonary fibrosis. However, the detailed mechanism is unknown. Our study aimed to investigate the role of the NLRP3 inflammasome in the regulation of EndoMT in pulmonary fibrosis. The inhibition of the NLRP3 inflammasome via a caspase-1 inhibitor, Ac-YVAD-cmk (YVAD), was intraperitoneally administered to male C57BL/6 mice (8-12 weeks old) one hour before bleomycin intratracheal injection (1.5 U/kg). Immunohistochemical staining, Masson's trichrome staining, enzyme-linked immunosorbent assay, immunofluorescence, and Western blotting were used to assess the activity of the NLRP3 inflammasome and EndoMT in lung samples from mice. Human pulmonary microvascular endothelial cells (HPMECs) were used as a model of EndoMT in vitro with YVAD and bleomycin stimulation. We observed the activation of the NLRP3 inflammasome and EndoMT (decreased vascular endothelial cadherin with increased alpha-smooth muscle actin and vimentin) in the lung samples after bleomycin. However, inhibition of the NLRP3 inflammasome significantly reduces EndoMT via inhibiting focal adhesion kinase (FAK). In vitro studies also confirmed these findings. In conclusion, NLRP3 inflammasome inhibition could reduce lung inflammation and fibrosis via the regulation of EndoMT by the FAK pathway.

Preparation of Highly Reactive Lithium Metal Dendrites for the Synthesis of Organolithium Reagents.

A long-standing problem in the area of organolithium chemistry has been the need for a highly reactive Li-metal source that mimics Li-powders but has the advantage of being freshly prepared from inexpensive and readily available Li-sources. Here, we report a simple and convenient activation method using liquid ammonia that furnishes a new Li-metal source in the form of crystalline Li-dendrites. The Li-dendrites were shown to have ca. 100 times greater surface area than conventional Li-sources created by prototypical mechanical activation methods. Concomitant with the surface area increase, the Li-dendrites were shown to exhibit significant rate enhancements over Li-powders, which are currently the industry standard for the preparation of organolithium compounds. These features were leveraged for the reproducible synthesis of organolithium reagents over a range of common laboratory scales.

Treatment Patterns and Outcomes in Patients with Esophageal Cancer: An Analysis of a Multidisciplinary Tumor Board Database.

BACKGROUND: Multidisciplinary management strategies are standard in esophageal cancer. Based on a multidisciplinary tumor board (MTB) database in a high-volume center, we aimed to evaluate real-world treatment patterns and patient outcomes in patients with esophageal cancer. In addition, we determined the impact of MTB discussions on patient prognosis. METHODS: Patients diagnosed with esophageal cancer between 2010 and 2019 were retrospectively reviewed. The pattern of treatment modalities and overall survival (OS) of patients with limited, locally advanced, and advanced/metastatic disease were reported. RESULTS: Data from 1132 patients, including 247 patients with limited esophageal cancer, 606 patients with locally advanced esophageal cancer, and 279 patients with advanced/metastatic esophageal cancer were included. Upfront surgery was the most common (56.3%) treatment modality for patients with limited esophageal cancer, while treatment for locally advanced esophageal cancer included upfront surgery (19.1%), neoadjuvant chemoradiotherapy (44.9%), and definitive chemoradiotherapy (36.0%); however, 27.9% of patients undergoing neoadjuvant chemoradiotherapy did not receive planned esophagectomy. Definitive chemoradiotherapy was mainly used for patients with locally advanced and advanced/metastatic disease, but had an incompletion rate of 22.0% and 33.7%, respectively. Regarding survival, the 5-year OS rates were 56.4%, 26.3%, and 5.1% in patients with limited, locally advanced, and advanced/metastatic disease, respectively. Additionally, patients whose clinical management was discussed in the MTB had a significantly better 5-year OS rate than the other patients (27.3% vs. 20.5%, p < 0.001). CONCLUSIONS: We report the real-world data of treatment patterns and patient outcomes in patients with esophageal cancer with respect to multidisciplinary management, and demonstrate the positive impact of MTB discussions on patient prognosis.

Post-recurrence survival analysis in patients with oligo-recurrence after curative esophagectomy.

BACKGROUND: Recurrent esophageal cancer is associated with dismal prognosis. There is no consensus about the role of surgical treatments in patients with limited recurrences. This study aimed to evaluate the role of surgical resection in patients with resectable recurrences after curative esophagectomy and to identify their prognostic factors. METHODS: We retrospectively reviewed patients with recurrent esophageal cancer after curative esophagectomy between 2004 and 2017 and included those with oligo-recurrence that was amenable for surgical intent. The prognostic factors of overall survival (OS) and post-recurrence survival (PRS), as well as the survival impact of surgical resection, were analyzed. RESULTS: Among 654 patients after curative esophagectomies reviewed, 284 (43.4%) had disease recurrences. The recurrences were found resectable in 63 (9.6%) patients, and 30 (4.6%) patients received surgery. The significant prognostic factors of PRS with poor outcome included mediastinum lymph node (LN) recurrence and pathologic T3 stage. In patients with and without surgical resection for recurrence cancer, the 3-year OS rates were 65.6 and 47.6% (p = 0.108), while the 3-year PRS rates were 42.9 and 23.5% (p = 0.100). In the subgroup analysis, surgery for resectable recurrence, compared with non-surgery, could achieve better PRS for patients without any comorbidities (hazard ratio 0.36, 95% CI: 0.14 to 0.94, p = 0.038). CONCLUSIONS: Mediastinum LN recurrence or pathologic T3 was associated with worse OS and PRS in patients with oligo-recurrences after curative esophagectomies. No definite survival benefit was noted in patients undergoing surgery for resectable recurrence, except in those without comorbidities.

Association of left ventricular global area strain derived from resting 3D speckle-tracking echocardiography and exercise capacity in individuals undergoing treadmill exercise test.

Background: Left ventricular (LV) global area strain (GAS) is a novel index derived from resting 3D speckle-tracking echocardiography (STE), and its clinical significance has rarely been studied. We examined the association of LV GAS and exercise capacity in a health check-up population. Methods: We recruited 94 symptom-free participants (52.2 ± 11.7 years, 62.8% male) without substantial structural heart disease or coronary heart diseases who were undergoing a routine health examination. All participants underwent resting echocardiography and symptom-limited treadmill exercise test according to the Bruce protocol. Four strain parameters were obtained from the analysis, namely 3D GAS (GAS3d), global longitudinal strain, global circumferential strain, and global radial strain. Results: After multivariate analysis for factors of exercise time, we observed a significant association in LV GAS3d (P < 0.001). We divided participants into preserved and impaired exercise capacity groups according to the cutoff value of 8 metabolic equivalent of tasks. LV GAS3d (OR 1.24, 95% CI 1.10-1.39, P < 0.001) was an independent predictor of impaired exercise capacity and the optimal cut-off value was -19.96% at a sensitivity of 77.8% and at a specificity of 92.1%. LV GAS3d could improve the discriminatory power of exercise capacity in individuals with early mitral filling velocity to average mitral annulus velocity ratio (E/e') ≥ 8. Conclusions: LV GAS3d was significantly associated with exercise time and exhibited incremental predictive value on E/e' for exercise capacity in participants undergoing treadmill exercise test.

Two-thirds anteroposterior ramus length is the preferred osteotomy point for intraoral vertical ramus osteotomy.

OBJECTIVES: This study aimed to investigate the mandibular canal of ramus and design a suitable osteotomy line for intraoral vertical ramus osteotomy (IVRO) using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Ninety patients were classified into class I, II, and III skeletal pattern groups. When extended from the horizontal base plane (0 mm, mandibular foramen [MF]), with a 2-mm section interval, to 10 mm above and 10 mm below the MF, the following landmarks were identified: external oblique ridge (EOR), posterior border of the ramus (PBR), and posterior lateral cortex of ramus (PLC): IVRO osteotomy point. RESULTS: In the base plane (0-mm plane), the EOR-PBR distance of class III (34.78 mm) and the IOR-PBR distance of class II (32.72 mm) were significantly higher than those of class I (32.95 mm and 30.03 mm). Compared to the EOR-PLC distance, the designed osteotomy point (two-thirds EOR-PBR length) has a 3.49-mm safe zone at the base plane and ranging from 0.89 mm (+ 10-mm plane) to 8.37 mm (- 10-mm plane). CONCLUSIONS: The position at two-thirds EOR-PBR length (anteroposterior diameter of the ramus) can serve as a reference distance for the IVRO osteotomy position. CLINICAL RELEVANCE: Mandibular setback operations for treating mandibular prognathism mainly include sagittal split ramus osteotomy (SSRO) and IVRO. IVRO has a markedly lower incidence of postoperative lower lip paraesthesia than SSRO. Our design presented a reference point for identification during IVRO, to prevent damage to the inferior alveolar neurovascular bundle.

Clinical significance of postoperative skeletal relapse in the treatment of mandibular prognathism: Receiver operating characteristic curve analysis.

BACKGROUND/PURPOSE: Postoperative skeletal relapse is the most important issue in patients undergoing orthognathic surgery. This study aimed to investigate clinical skeletal relapse (≥2 mm) after mandibular setback surgery (intraoral vertical ramus osteotomy: IVRO) using receiver operating characteristic curve (ROC curve) analysis. METHODS: Serial cephalograms of 40 patients with mandibular prognathism were obtained at different time points: (1) before surgery (T1), (2) immediately after surgery (T2), and (3) at least with a 2-year follow-up postoperatively (T3). The menton (Me) was used as the landmark for measuring the amount of mandibular setback and postoperative skeletal relapse. Postoperative stability (T32) was divided into groups A and B by skeletal relapse ≥2 mm and <2 mm, respectively. The area under the ROC curve (AUC) was used to determine the cut-off point for mandibular setback. RESULTS: At the immediate surgical setback (T21), the amount of setback in group A (15.55 mm) was significantly larger than in group B (10.97 mm). Group A (T32) showed a significant relapse (4.07 mm), while group B showed a significant posterior drift (1.23 mm). The amount of setback had the highest AUC area (0.788). The cut-off point was 14.1 mm (T21) that would lead to a clinical relapse of 2 mm (T32). CONCLUSION: In IVRO, the postoperative mandibular positions reveal posterior drift and anterior displacement (relapse). The experience of clinical observation and patient perception of postoperative skeletal relapse was ≥2 mm. In the ROC curve analysis, the cut-off point of setback was 14.1 mm.

Retrospective analysis of primary intraosseous malignancies in mandible and maxilla in a population of Taiwanese patients.

BACKGROUND/PURPOSE: Due to the rarity and diversity of primary intraosseous malignancies in jawbones, we aimed to evaluate the clinicopathological features and discuss the findings of our collected cases with the literatures. METHODS: Twenty-nine patients (2000-2020) diagnosed with primary central malignancies of jawbones were selected from the database of Oral Pathology Department in our institution. Clinical features, radiographic appearance, and histopathological diagnosis of the 29 cases were analyzed. RESULTS: Twenty-nine patients aged between 19 and 84 years (average, 57.4 years) with a male to female ratio of 1.2:1 were included. The most frequent site was the mandibular body and ramus, followed by the posterior maxilla and mandibular symphysis. The most common diagnosis was osteogenic sarcoma (n = 13), followed by odontogenic carcinoma (n = 7), hematologic malignancies (n = 5), salivary gland malignancies (n = 2), and neurogenic sarcomas (n = 2). The most frequent symptoms were swelling, pain, paresthesia of lower lip, and mobile tooth. Radiographically, they usually presented as ill-defined osteolytic to osteoblastic lesions depending on the amount of ossification. Wide excision comprising partial maxillectomy and segmental mandibulectomy were the most common therapeutic methods. CONCLUSION: Despite the rarity of primary central malignancies in jawbones, the clinical features may mimic infectious process or benign lesions. Detailed history-taking, clinical and imaging examination and awareness of the patient's signs and symptoms combining with the histopathological inspection are important for early diagnosis and improved prognosis. The current data contributes a useful basis for clinical investigation regarding intraosseous malignancies occurring in the jawbones.

Experimental evolution can enhance benefits of rhizobia to novel legume hosts.

Legumes preferentially associate with and reward beneficial rhizobia in root nodules, but the processes by which rhizobia evolve to provide benefits to novel hosts remain poorly understood. Using cycles of in planta and in vitro evolution, we experimentally simulated lifestyles where rhizobia repeatedly interact with novel plant genotypes with which they initially provide negligible benefits. Using a full-factorial replicated design, we independently evolved two rhizobia strains in associations with each of two Lotus japonicus genotypes that vary in regulation of nodule formation. We evaluated phenotypic evolution of rhizobia by quantifying fitness, growth effects and histological features on hosts, and molecular evolution via genome resequencing. Rhizobia evolved enhanced host benefits and caused changes in nodule development in one of the four host-symbiont combinations, that appeared to be driven by reduced costs during symbiosis, rather than increased nitrogen fixation. Descendant populations included genetic changes that could alter rhizobial infection or proliferation in host tissues, but lack of evidence for fixation of these mutations weakens the results. Evolution of enhanced rhizobial benefits occurred only in a subset of experiments, suggesting a role for host-symbiont genotype interactions in mediating the evolution of enhanced benefits from symbionts.

Clinicopathological Significance of Pathologic Complete Lymph Node Regression After Neoadjuvant Chemoradiotherapy in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Pathologic complete lymph node regression (LNR), where the lymph nodes show evidence of neoadjuvant treatment effect but have no viable residual tumor cells, is sometimes observed following neoadjuvant treatments and has been shown to be prognostic; conflicting results exist in the current literature. METHODS: Patients who received neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy for squamous carcinoma (ESCC) were retrospectively reviewed and classified according to their LNR score; 0: N(-) with no evidence of tumor involvement or regression; 1: N(-) with evidence of complete regression; 2: N(+) with < 50% viable tumor; and 3: N(+) with > 50% viable tumor. RESULTS: In total, 136 patients, comprising 73, 25, 16, and 22 patients with LNR scores of 0, 1, 2, or 3, respectively, were included. Pathologic complete LNR (LNR 1) was significantly associated with lower risks of lymphovascular invasion (0%, p < 0.001) and perineural invasion (4%, p = 0.038), and a higher rate of pathologic complete response in the primary tumor (76%, p < 0.001). The 5-year overall survival rates were 42.1%, 52.8%, and 8.0% in patients with an LNR score of 0, 1, and 2/3, respectively (p < 0.001). There was no significant difference between patients with LNR scores of 0 and 1 in overall survival (p = 0.454), disease-free survival (p = 0.501), and cumulative incidence of recurrences (hazard ratio 0.84, 95% confidence interval 0.432-1.623, p = 0.601). CONCLUSIONS: Pathologic complete LNR could be an indicator of nCRT sensitivity and can be regarded as a good prognostic factor in patients with ESCC. In the survival curve analysis that included patients with lymph node regression (LNR) scores of 0 (blue), 1 (red), and 2/3 (green), we found that patients with pathologic complete LNR (LNR 1), which suggests prior positive nodal involvement, had similar outcomes as those without evidence of prior tumor involvement in lymph node (LNR0).

Maintenance of low driving pressure in patients with early acute respiratory distress syndrome significantly affects outcomes.

BACKGROUND: Driving pressure (∆P) is an important factor that predicts mortality in acute respiratory distress syndrome (ARDS). We test the hypothesis that serial changes in daily ΔP rather than Day 1 ΔP would better predict outcomes of patients with ARDS. METHODS: This retrospective cohort study enrolled patients admitted to five intensive care units (ICUs) at a medical center in Taiwan between March 2009 and January 2018 who met the criteria for ARDS and received the lung-protective ventilation strategy. ∆P was recorded daily for 3 consecutive days after the diagnosis of ARDS, and its correlation with 60-day survival was analyzed. RESULTS: A total of 224 patients were enrolled in the final analysis. The overall ICU and 60-day survival rates were 52.7% and 47.3%, respectively. ∆P on Days 1, 2, and 3 was significantly lower in the survival group than in the nonsurvival group (13.8 ± 3.4 vs. 14.8 ± 3.7, p = 0.0322, 14 ± 3.2 vs. 15 ± 3.5, p = 0.0194, 13.6 ± 3.2 vs. 15.1 ± 3.4, p = 0.0014, respectively). The patients were divided into four groups according to the daily changes in ∆P, namely, the low ∆P group (Day 1 ∆P < 14 cmH2O and Day 3 ∆P < 14 cmH2O), decrement group (Day 1 ∆P ≥ 14 cmH2O and Day 3 ∆P < 14 cmH2O), high ∆P group (Day 1 ∆P ≥ 14 cmH2O and Day 3 ∆P ≥ 14 cmH2O), and increment group (Day 1 ∆P < 14 cmH2O and Day 3 ∆P ≥ 14 cmH2O). The 60-day survival significantly differed among the four groups (log-rank test, p = 0.0271). Compared with the low ΔP group, patients in the decrement group did not have lower 60-day survival (adjusted hazard ratio 0.72; 95% confidence interval [CI] 0.31-1.68; p = 0.4448), while patients in the increment group had significantly lower 60-day survival (adjusted hazard ratio 1.96; 95% CI 1.11-3.44; p = 0.0198). CONCLUSIONS: Daily ∆P remains an important predicting factor for survival in patients with ARDS. Serial changes in daily ΔP might be more informative than a single Day 1 ΔP value in predicting survival of patients with ARDS.

Active surveillance or early resection for ground-glass nodules that need preoperative localization.

INTRODUCTION: Few studies have investigated the impact of active surveillance on pathological outcome ground-glass nodules (GGNs). We focused on GGNs that needed preoperative localization before resection and compared the pathological results between GGNs that underwent early resection or active surveillance. METHODS: We retrospectively reviewed data of resected GGNs between January 2017 and December 2018. GGNs were classified by early resection (Group A) and active surveillance (Group B). Group B was subclassified as no (Group B1) and with (Group B2) growth, and intergroup comparison of pathological results was undertaken. RESULTS: In total, 509 GGNs (124, 275, and 110 in Groups A, B1, and B2, respectively) were included. Malignancy (primary lung cancer) ratios were 68% and 72% in Groups A and B (p = .312) and 65% and 92% in Groups B1 and B2, respectively (p < .001). The ratios of invasive carcinoma were 21.4%, 9.6%, and 35.6% in Groups A, B1, and B2, respectively. Predictors for invasive carcinoma included history of lung cancer, GGN size ≥ 10 mm, solid size ≥ 6 mm, and GGN growth. CONCLUSIONS: The pathological findings were similar for GGNs in the early resection and active surveillance groups. However, rates of malignancy and invasive carcinoma increased in the group that manifested growth during active surveillance.