Δευτέρα 11 Οκτωβρίου 2021

Autologous reconstructions are associated with greater overall medium-term care costs than implant-based reconstructions in the Finnish healthcare system: A retrospective interim case-control cohort study

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J Plast Reconstr Aesthet Surg. 2021 Sep 17:S1748-6815(21)00407-1. doi: 10.1016/j.bjps.2021.08.020. Online ahead of print.

ABSTRACT

PURPOSE: Previous studies have mainly reported the short-term costs of different reconstruction techniques. Revision operations may increase costs in longer follow-up. Authors report medium-term data on different reconstruction methods. We hypothesised that the reconstruction method would affect not only the duration of reconstruction process but also total costs.

METHODS: The reconstruction database was reviewed from 2008 to 2019. Women with autologous (deep inferior epigastric perforator, transverse musculocutaneous gracilis and latissimus dorsi [LD] without implant) and implant-based (implant and LD with implant) reconstructions were included. Variables evaluated included age, body mass index, smoking, comorbidities, radiotherapy, complications and readmissions. Risk factors for multiple revision s urgeries were analysed. Time to definitive reconstruction and related costs were also calculated.

RESULTS: In total, 591 patients with autologous reconstructions and 202 with implant-based reconstructions were included. The median follow-up time was 73 months. Definitive reconstruction was obtained in 443 days in implant-based reconstructions and in 403 days in autologous reconstructions (P = 0.050). Independent risk factors for multiple surgeries were younger age (P < 0.001) and comorbidity (P = 0.008). No statistically significant difference was observed in the rate of overall surgical procedures (P = 0.098), but implant-based reconstructions were more commonly associated with two or more planned operations (P = 0.008). Autologous reconstructions were associated with greater total cost ($22 052 vs. $18 329, P < 0.001).

CONCLUSIONS: This review of reconstructions over a 12-year study period revealed that autologous reconstructions are associated with greater overa ll costs, but there is no statistically significant difference in reconstruction time or rate of surgical procedures. However, a full cost assessment between reconstructive techniques requires a much longer follow-up period.

PMID:34627717 | DOI:10.1016/j.bjps.2021.08.020

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Second dorsal metacarpal artery-based index finger dorsal island flap for the management of thumb defects

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J Plast Reconstr Aesthet Surg. 2021 Sep 17:S1748-6815(21)00403-4. doi: 10.1016/j.bjps.2021.08.016. Online ahead of print.

ABSTRACT

Index finger dorsal island flaps were frequently utilized by hand surgeons to reconstruct thumb defects. However, the blood supply of the traditional index finger dorsal island flap comes from the first dorsal metacarpal artery, which has a smaller diameter, more anatomical variation, and can be injured in conjunction with thumb injuries. Therefore, we design an alternative index finger dorsal island flap based on the second dorsal metacarpal artery to treat thumb skin defects. From August 2015 to October 2018, we used the index finger dorsal island flaps with the second dorsal metacarpal artery to treat 11 patients with thumb skin defects. All the flaps and skin grafts survived completely without complications. At the last follow-up, the mean 2PD of the flap was 6.4 mm (45.5% for excellent, 54.5% for good) , the mean ROM of the injured thumbs was 115.9° (72.7% for excellent, 27.3% for good), and the mean cosmetics score was 8.6. Our results demonstrate that the index finger dorsal island flap with the second dorsal metacarpal artery is suitable for the reconstruction of thumb skin defects. The flap has an excellent survival rate and good coverage with satisfactory results and represents a promising treatment for the selected patients. Level of Evidence: Therapeutic, level IV.

PMID:34627716 | DOI:10.1016/j.bjps.2021.08.016

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Treatment modalities, adverse events, and survival outcomes in older patients with head and neck squamous cell carcinoma

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Abstract

Background

Chemoradiation with curative intent in older adults with locally advanced head and neck squamous cell carcinoma (HNSCC) has been a challenge, because of its potential toxicities.

Methods

We selected primary HNSCC cases from the SEER-Medicare linked database, assessed overall survival (OS) and adverse events and their associations with different treatments, across four age groups including the youngest (66–69 years) and the oldest (≥80 years).

Results

Better OS was associated with chemoradiation compared to radiation alone, not only in all patients (N = 5879) (hazard ratio [HR] = 0.82, p < 0.001), but also in the oldest group (N = 1380) (HR = 0.77, p = 0.006) in whom the adverse events rates were not higher than those in the youngest (N = 1562); more of the latter (26%–30%) than the former (14%–19%) received chemoradiation, regardless of their comorbidity indices.

Conclusions

Our findings provide evidence that patients' characteristics, other than chronological age, should be equally considered in selecting the best therapy for older patients with HNSCC.

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Primary Ewing's sarcoma with orbit involvement: Survival and visual outcomes after eye‐sparing multidisciplinary management in eight patients

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Abstract

Background

To describe the clinical presentation, treatment, and overall prognosis in eight patients with primary Ewing's sarcoma (ES) involving the orbit.

Methods

A retrospective interventional study of all biopsy-proven cases of primary ES involving the orbit was done.

Results

There were seven males and one female with a median age of 14 years. Imaging showed osseous involvement in all eight cases with extraorbital extension in four. Complete tumor resection was done in four, partial resection in three, and biopsy followed by sinus surgery in one. EWSR1 gene rearrangement analysis was done to confirm diagnosis. All patients received multidrug systemic chemotherapy and seven patients received adjuvant radiotherapy. Eye salvage was achieved in all patients. At a mean follow-up duration of 52.63 months, seven patients were doing well with no evidence of disease.

Conclusions

ES involving the orbit is sensitive to chemotherapy and radiation. Aggressive multimodality treatment can help salvage the globe and improve overall survival.

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Renal tumor biomarkers (Review)

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Exp Ther Med. 2021 Nov;22(5):1297. doi: 10.3892/etm.2021.10732. Epub 2021 Sep 14.

ABSTRACT

One of the most common types of cancer worldwide (9th most commonly diagnosed) is renal cell carcinoma (RCC). It is more common in developed countries and it usually develops in individuals between 60 and 70 years of age. The earlier the disease is identified, the lower the morbidity. Therefore molecular markers that exist in blood and urine may be used for earlier detection and diagnosis but also for the follow-up of the patient after treatment, whether surgical or oncological. The trend is to analyze the gene and protein expression as they constitute a source for new biomarkers. These markers are promising but in clinical practice regarding disease management, they are rarely used. Biological markers can be employed in many tumors because they can identify the prognostic value for individual treatment. However, markers for RCC are not validated , and their analysis is currently under investigation. Previous findings have demonstrated that the metastatic potential of RCC can be predicted using the biological features of the tumor cell. It is believed that the transformation from epithelial to mesenchymal phenotype gives the tumor cell the ability to metastasize. The purpose of this review was to identify the most valuable tumor markers that can be clinically used for the prognosis, treatment and follow-up of patients with renal tumors.

PMID:34630652 | PMC:PMC8461509 | DOI:10.3892/etm.2021.10732

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miR-489-3p overexpression inhibits lipopolysaccharide-induced nucleus pulposus cell apoptosis, inflammation and extracellular matrix degradation via targeting Toll-like receptor 4

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Exp Ther Med. 2021 Nov;22(5):1323. doi: 10.3892/etm.2021.10758. Epub 2021 Sep 20.

ABSTRACT

Intervertebral disc degeneration (IDD) is a common disease with a high morbidity rate, which results in a significant deterioration in the quality of life of patients. MicroRNAs (miRNAs/miRs) are a class of endogenous small non-coding RNAs that influence target genes and serve critical roles in numerous biological processes. However, the role of miR-489-3p in lumbar disc degeneration is yet to be elucidated. In the present study, human NP cells were treated with 10 ng/ml lipopolysaccharide (LPS) for 24 h to investigate the role of miR-489-3p in IDD in an in vitro model. Reverse transcription-quantitative (RT-q)PCR was performed to determine the expression levels of miR-489-3p. Then, the TargetScan database was used to predict the potential binding sites between miR-489-3p and Toll-like receptor (TLR)4, and a dual-luciferase reporter assay was performed to verify the findings. Subsequently, RT-qPCR and western blotting were used to analyze the expression levels of TLR4. In addition, human nucleus pulposus (NP) cells were transfected with a miR-489-3p mimic and TLR4 overexpression plasmid to study the effects of miR-489-3p on LPS-induced human NP cells. Cell apoptosis and cell viability were also determined using flow cytometry and MTT assays, respectively. Finally, ELISAs were performed to analyze the levels of inflammatory factors. The expression levels of miR-489-3p were discovered to be downregulated in LPS-treated human NP cells. In addition, TLR4 was revealed to be a direct target gene of miR-489-3p, and its expression levels were upregulated in LPS-treated human NP cells. miR-489-3p was found to inhibit the LPS-induced decreases in cell viability and increases in apoptosis, and the concentration of inflammatory cytokines. Furthermore, miR-489-3p suppressed the LPS-induced decreases in extracellular matrix deposi tion via decreasing the expression levels of aggrecan and collagen type II in human NP cells. Finally, the results revealed that miR-489-3p inhibited the LPS-induced activation of the NF-κB signaling pathway in human NP cells. Conversely, all of the effects of miR-489-3p on LPS-induced human NP cells were reversed by the TLR4 overexpression plasmid. These findings suggested that miR-489-3p may represent a novel therapeutic target for the treatment of IDD.

PMID:34630677 | PMC:PMC8495590 | DOI:10.3892/etm.2021.10758

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Honokiol combined with curcumin sensitizes multidrug-resistant human lung adenocarcinoma A549/DDP cells to cisplatin

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Exp Ther Med. 2021 Nov;22(5):1301. doi: 10.3892/etm.2021.10736. Epub 2021 Sep 16.

ABSTRACT

The aim of the present study was to discuss the effects and underlying mechanisms of honokiol (HNK) and/or curcumin (CUR) in sensitization of multidrug-resistant human lung adenocarcinoma A549/DDP cells to cisplatin (DDP). An MTS assay was performed to detect the cytotoxicity of HNK, CUR and DDP in A549 and A549/DDP cells and compare their sensitivity. The A549/DDP cells were then divided into 8 groups: Control, HNK, CUR, DDP, HNK + CUR, HNK + DDP, CUR + DDP and HNK + CUR + DDP. Cell proliferation was measured by MTS assay and colony formation assay, cell apoptosis was detected by flow cytometry, cell invasion was evaluated by Transwell assay and cell migration was determined by a wound healing assay. In order to investigate the possible mechanisms, P-glycoprotein (P-gp) protein expression was measured by western blotting and immunofluorescence a ssays. The mRNA expression levels of AKT, Erk1/2, cyclin-dependent kinase inhibitor 1 (P21), caspase 3, cleaved caspase 3, caspase 9, cleaved caspase 9, poly (ADP-ribose) polymerase (PARP), cleaved PARP, matrix metalloproteinase (MMP)-2 and MMP-9 were examined by reverse transcription-quantitative (RT-q) PCR assay, and the protein expression levels of phosphorylated (p)-AKT, p-Erk1/2, P21, caspase 3, cleaved caspase 3, caspase 9, cleaved caspase 9, PARP, cleaved PARP, MMP-2 and MMP-9 proteins expression by western blot assay. The MTS assay demonstrated that HNK (5 µg/ml), CUR (10 µg/ml) and DDP (5 µg/ml) had no obvious toxicity to A549/DDP cells, and HNK, CUR and DDP were more sensitive in A549 cells compared with A549/DDP cells. The optimal concentrations of HNK (5 µg/ml), CUR (10 µg/ml) and DDP (5 µg/ml) were chosen to carry out the further experiments. Compared with the control group, no significant change was observed in cell proliferation, apoptosis, migration, invasion a nd related mRNA and protein expression in HNK, CUR, DDP and HNK + CUR groups. The cell proliferation rate in the HNK + DDP and CUR + DDP groups was significantly suppressed with cell apoptosis significantly increased, respectively. The invasion cell number and wound healing rate of HNK + DDP and CUR + DDP groups were significantly depressed compared with the control group, respectively. Immunofluorescence demonstrated that the nuclear volume of P-gp in HNK + DDP and CUR + DDP groups were significantly downregulated compared with the control group, respectively. The RT-qPCR assay demonstrated that the AKT, Erk1/2 and P21 mRNA expression levels were significantly decreased and cleaved caspase 3, cleaved caspase 9 and cleaved PARP were increased in HNK + DDP and CUR + DDP groups compared with the control group. The western blotting results were consistent with the RT-qPCR results. NK + CUR + DDP had improved effects on A549/DDP compared with HNK + DDP or CUR + DDP group, respectively. HNK and/or CUR could improve the sensitivity of DDP to A549/DDP cell by the regulation of P-gp, inducing apoptosis, and inhibiting migration and invasion via AKT/ERK signal pathway in an in vitro study.

PMID:34630656 | PMC:PMC8461625 | DOI:10.3892/etm.2021.10736

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Efficacy and safety of tenofovir alafenamide fumarate in nucleoside analogue treatment-naïve patients with chronic hepatitis B

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Exp Ther Med. 2021 Nov;22(5):1325. doi: 10.3892/etm.2021.10760. Epub 2021 Sep 20.

ABSTRACT

Tenofovir alafenamide fumarate (TAF) is a first-line drug for the antiviral treatment of patients with chronic hepatitis B (CHB) in China. In the present study, the efficacy and renal safety of TAF were evaluated in treatment-naive patients with CHB. Patients with CHB who had not been previously treated with nucleoside analogues (NAs) were recruited before TAF treatment was initiated. Changes in the levels of hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were analyzed at 24 and 48 weeks using immunoassays. In addition, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were analyzed using transient elastography, while alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels, calcium (Ca) and inorga nic phosphorus (IP) levels were measured using biochemistry assay. In addition, the estimated glomerular filtration rate (eGFR) was calculated. After 48 weeks, the ALT normalization rate was 95.24% (40/42), the complete virological response (HBV DNA <20 IU/ml) rate was 69.05% (29/42) and the HBeAg seroconversion rate was 8.57% (3/35). The levels of HBV DNA and HBsAg were significantly decreased from the baseline at 5.49±1.95 to 1.26±0.66 log10 IU/ml and from 3.59±0.81 to 3.32±0.55 log10 IU/ml after 48 weeks of treatment, respectively. Compared with that in the baseline measurements, LSM at 48 weeks was significantly decreased from 13.00±8.15 to 8.66±4.45 kPa. No significant differences were observed in the TG, TC, LDL-C, CAP, eGFR, Ca and IP measurements. According to the baseline ALT levels, patients were divided into group A [ALT ≤1 x upper limit of normal (ULN); ULN=50 U/l; n=21], group B (1 x ULN < ALT <2 x ULN; n=22) and group C (ALT ≥2 x ULN; n=18). A significant decrease in HBsAg levels was observed in group B (3.63±0.68 vs. 3.53±0.63 log10 IU/ml) and group C (4.15±0.57 vs. 3.66±0.48 log10 IU/ml) at 24 weeks compared with the baseline. In conclusion, TAF was found to be effective and safe in NA treatment-naive patients with CHB. Moreover, the higher the ALT levels, the more prominent the curative effect from TAF treatment. Therefore, NA treatment-naive CHB patients could benefit from TAF treatment in real world.

PMID:34630679 | PMC:PMC8495544 | DOI:10.3892/etm.2021.10760

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Research progress on evodiamine, a bioactive alkaloid of Evodiae fructus: Focus on its anti-cancer activity and bioavailability (Review)

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Exp Ther Med. 2021 Nov;22(5):1327. doi: 10.3892/etm.2021.10762. Epub 2021 Sep 20.

ABSTRACT

Evodiae fructus (Wu-Zhu-Yu in Chinese) can be isolated from the dried, unripe fruits of Tetradium ruticarpum and is a well-known traditional Chinese medicine that is applied extensively in China, Japan and Korea. Evodiae fructus has been traditionally used to treat headaches, abdominal pain and menorrhalgia. In addition, it is widely used as a dietary supplement to provide carboxylic acids, essential oils and flavonoids. Evodiamine (EVO) is one of the major bioactive components contained within Evodiae fructus and is considered to be a potential candidate anti-cancer agent. EVO has been reported to exert anti-cancer effects by inhibiting cell proliferation, invasion and metastasis, whilst inducing apoptosis in numerous types of cancer cells. However, EVO is susceptible to metabolism and may inhibit the activities of me tabolizing enzymes, such as cytochrome P450. Clinical application of EVO in the treatment of cancers may prove difficult due to poor bioavailability and potential toxicity due to metabolism. Currently, novel drug carriers involving the use of solid dispersion techniques, phospholipids and nanocomplexes to deliver EVO to improve its bioavailability and mitigate side effects have been tested. The present review aims to summarize the reported anti-cancer effects of EVO whilst discussing the pharmacokinetic behaviors, characteristics and effective delivery systems of EVO.

PMID:34630681 | PMC:PMC8495584 | DOI:10.3892/etm.2021.10762

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Yiqi Huoxue preserves heart function by upregulating the Sigma-1 receptor in rats with myocardial infarction

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Exp Ther Med. 2021 Nov;22(5):1308. doi: 10.3892/etm.2021.10743. Epub 2021 Sep 16.

ABSTRACT

Yiqi Huoxue (YQHX) is widely used in traditional Chinese medical practice due to its reported cardioprotective effects. The aim of the present study was to investigate the mechanism underlying these effects of YQHX via the regulation of the Sigma-1 receptor. The Sigma-1 receptor is a chaperone protein located on the mitochondrion-associated endoplasmic reticulum (ER) membrane. It serves an important role in heart function by regulating intracellular Ca2+ homeostasis and enhancing cellular bioenergetics. In the present study, male Sprague Dawley rats with myocardial infarction (MI)-induced heart failure were used. MI rats were administered different treatments, including normal saline, YQHX and fluvoxamine, an agonist of the Sigma-1 receptor. Following four weeks of treatment, YQHX was revealed to improve heart function and attenuate my ocardial hypertrophy in MI rats. Additionally, YQHX increased the ATP content and improved the mitochondrial ultrastructure in the heart tissues of MI rats in comparison with acontrol. Treatment was revealed to attenuate the decreased expression of the Sigma-1 receptor and increase the expression of inositol triphosphate type 2 receptors (IP3R2) in MI rats. By exposing H9c2 cells to angiotensin II (Ang II), YQHX prevented cell hypertrophy and normalized the decreased ATP content. However, these positive effects were partially inhibited when the Sigma-1 receptor was knocked down via small interfering RNA transfection. The results of the present study suggested that the Sigma-1 receptor serves an important role in the cardioprotective efficacy of YQHX by increasing ATP content and attenuating cardiomyocyte hypertrophy.

PMID:34630662 | PMC:PMC8461621 | DOI:10.3892/etm.2021.10743

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