Background
We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps.
...Methods
From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (
n
= 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable.
Results
Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3−4, pN1−3, p-Stage III−IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all
p
< 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival OS), age ≥ 65 years, pT3−4, pN1−3, p-Stage III−IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio HR 1.26, 82%/77%;
p
= 0.0100) and OS (HR 1.21, 73%/68%;
p
= 0.0079).
Conclusions
After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.
Abstract
Titanium dioxide (TiO
2
) is one of the most common compounds on Earth, and it is used in natural forms or engineered bulks or nanoparticles (NPs) with increasing rates. However, the effect ...of TiO
2
NPs on plants remains controversial. Previous studies demonstrated that TiO
2
NPs are toxic to plants, because the photocatalytic property of TiO
2
produces biohazardous reactive oxygen species. In contrast, another line of evidence suggested that TiO
2
NPs are beneficial to plant growth. To verify this argument, in this study, we used seed germination of amaranth and cruciferous vegetables as a model system. Intriguingly, our data suggested that the controversy was due to the dosage effect. The photocatalytic activity of TiO
2
NPs positively affected seed germination and growth through gibberellins in a plant-tolerable range (0.1 and 0.2 mg/cm
2
), whereas overdosing (1 mg/cm
2
) induced tissue damage. Given that plants are the foundations of the ecosystem; these findings are useful for agricultural application, sustainable development and maintenance of healthy environments.
•Several studies indicated that margins < 1 mm should be classified as positive margins in OCSCC.•Margin < 1 mm exhibited distinct clinicopathological characteristics and a more favorable ...prognosis.•Positive margins should remain a high risk factor, whereas margins < 1 mm could be considered an intermediate risk factor.
While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm.
Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted.
The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio HR = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398).
OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins.
We conducted a cross-sectional study to clarify the relationship between oral health and physical frailty (PF). A sample of 903 community-dwelling individuals aged ≥ 65 years were enrolled from ...random communities in Chiayi County. The self-perceived oral health (SPOH) and oral health assessment tool (OHAT), which consists of eight items, was used for the evaluation of their oral health status. PF was assessed based on the Study of Osteoporotic Fracture index. Overall, 14.6% of the participants had PF. In an adjusted model, restricted food types (odds ratio (OR) = 1.59, 95% confidence interval (CI): 1.2–2.09, p = 0.001), self-reported dental status (OR = 1.61, 95% CI: 1.2–2.15, p = 0.001), number of teeth (OR = 0.98, 95% CI: 0.96–0.99, p = 0.006), frequency of tooth cleaning (OR = 0.83, 95% CI: 0.68–1.0, p = 0.049), OHAT score (OR = 1.09, 95% CI: 1.02–1.17, p < 0.017), and saliva items of OHAT (OR = 1.52, 95% CI: 1.11–2.1, p = 0.010) were significantly associated with PF. SPOH is a crucial indicator of PF; longitudinal analyses are necessary to understand the underlying pathway of risk factors for frailty onset.
Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent ...(0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase).
We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis.
Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 95% CI, 0.40-0.98), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 95% CI, 0.88-3.69), but better 90-day modified Rankin Scale score (functional independence modified Rankin Scale score, 0-2, 47% versus 31%; adjusted odds ratio, 1.91 95% CI, 1.28-2.86), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 95% CI, 0.43-1.25) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata.
Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.
The fluvial landscape of the Hengchun Peninsula in southernmost Taiwan is generally characterized by a narrow river and a wide valley plain. Such underfit stream features are unusual in tectonically ...active areas such as Taiwan. In this research, we hypothesize that the relative sea level change since the end of the last glacial period might be the main factor driving the formation of this type of landscape on the relatively recently emerged Taiwan Island. The Gangkou River is among the largest and most pristine rivers on the Hengchun Peninsula, and well-preserved river terraces and bedrock exposures occur along the river and river mouth. Therefore, the Gangkou River was thoroughly surveyed to investigate the factors shaping the landscape and to determine the landscape evolutionary history. Our research indicates that the average uplift rate of the Gangkou River is 1.5 - 1.7 mm yr^(-1). Because of the low uplift rate, the rising sea level after the last glaciation caused widespread aggradation in the Gangkou River. At approximately 8.0 - 7.7 ka, maximum flooding occurred, and the sea level subsequently remained stable, while the aggradation stopped after 7.1 ka. Incision followed, forming the high terraces, and starting in the Little Ice Age, repeated aggradation and incision occurred, forming the low terraces. These processes produced the current landscape of the Gangkou River. Overall, the uplift rates calculated from this research are relatively low in this tectonically active area.
Excessive accumulation of cadmium is known to cause nephrotoxicity by targeting renal proximal tubular epithelial cells. Studies showed an essential role of autophagy in cadmium-induced ...nephrotoxicity; however, its underlying mechanisms accompanied by autophagy are incompletely understood. Using an HK-2 human renal proximal tubular epithelial cell line as a study model, sustained exposure of cadmium chloride (CdCl2) was shown to cause cell viability loss, which was alleviated by inhibitors of autophagy but not apoptosis. Data from molecular and biochemical studies revealed an induction of autophagy proteins, intracellular acidic vesicles, and autophagic flux in CdCl2-treated cells. However, there was little sign of apoptosis-related changes. Pharmacological and genetic studies indicated an elevation of Endoplasmic Reticulum (ER) stress, Forkhead Box Class O (FoxO3a), Bcl-2 Interacting Protein 3 (Bnip3), and Beclin1, as well as their involvement in cadmium-induced autophagy and autophagic cell death. Renal injury, histological changes, and molecular marker of ER stress, FoxO3a, Bnip3, and autophagy were observed in the kidney cortex of CdCl2-exposed Sprague-Dawley rats. These observations indicate that ER stress, FoxO3a, Bnip3, and autophagy signaling were actively involved in cadmium-induced nephrotoxicity. Additionally, FoxO3a may act as a linking molecule to convey ER stress signals to Bnip3 and autophagy machinery upon cadmium exposure.
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•Cadmium causes autophagic cell death in HK-2 cells and kidney of exposed rats.•Cadmium induces ER stress and increases FoxO3a, Beclin1, and Bnip3 expression.•Inhibitors of ER stress alleviate cadmium-induced FoxO3a, Beclin1, and Bnip3 expression and autophagy.•FoxO3a silencing alleviates cadmium-induced Beclin1 and Bnip3 expression and autophagy.
Protein-bound uremic toxins, such as p-cresol sulfate (PCS), can be accumulated with declined renal function and aging and is closely linked with central nervous system (CNS) diseases. In the ...periphery, PCS has effects on oxidative stress and inflammation. Since oxidative stress and inflammation have substantial roles in the pathogenesis of neurological disorders, the CNS effects of PCS were investigated in unilateral nephrectomized C57/BL/6 mice. Unlike intact mice, unilateral nephrectomized mice showed increased circulating levels of PCS after exogenous administration. Upon PCS exposure, the unilateral nephrectomized mice developed depression-like, anxiety-like, and cognitive impairment behaviors with brain PCS accumulation in comparison with the nephrectomy-only group. In the prefrontal cortical tissues, neuronal cell survival and neurogenesis were impaired along with increased apoptosis, oxidative stress, and neuroinflammation. Circulating brain-derived neurotrophic factors (BDNF) and serotonin were decreased in association with increased corticosterone and repressor element-1 silencing transcription factor (REST), regulators involved in neurological disorders. On the contrary, these PCS-induced changes were alleviated by uremic toxin absorbent AST-120. Taken together, PCS administration in mice with nephrectomy contributed to neurological disorders with increased oxidative stress and neuroinflammation, which were alleviated by PCS chelation. It is suggested that PCS may be a therapeutic target for chronic kidney disease-associated CNS diseases.
In this study, we report a serum-free culture system for primary neonatal pulmonary cells that can support the growth of octamerbinding transcription factor 4⁺ (Oct-4⁺) epithelial colonies with a ...surrounding mesenchymal stroma. In addition to Oct-4, these cells also express other stem cell markers such as stage-specific embryonic antigen 1 (SSEA-1), stem cell antigen 1 (Sca-1), and Clara cell secretion protein (CCSP) but not c-Kit, CD34, and p63, indicating that they represent a subpopulation of Clara cells that have been implicated as lung stem/progenitor cells in lung injury models. These colony cells can be kept for weeks in primary cultures and undergo terminal differentiation to alveolar type-2- and type-1-like pneumocytes sequentially when removed from the stroma. In addition, we have demonstrated the presence of Oct-4⁺ long-term BrdU label-retaining cells at the bronchoalveolar junction of neonatal lung, providing a link between the Oct-4⁺ cells in vivo and in vitro and strengthening their identity as putative neonatal lung stem/progenitor cells. Lastly, these Oct-4⁺ epithelial colony cells, which also express angiotensin-converting enzyme 2, are the target cells for severe acute respiratory syndrome coronavirus infection in primary cultures and support active virus replication leading to their own destruction. These observations imply the possible involvement of lung stem/progenitor cells, in addition to pneumocytes, in severe acute respiratory syndrome coronavirus infection, accounting for the continued deterioration of lung tissues and apparent loss of capacity for lung repair.