Δευτέρα 29 Μαρτίου 2021

Congenital dyserythropoietic anemia and drug-induced liver injury present as bland cholestasis: A case report

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Exp Ther Med. 2021 May;21(5):456. doi: 10.3892/etm.2021.9887. Epub 2021 Mar 2.

ABSTRACT

Anemias and drug-induced liver injury(DILI) are separate disorders, which are difficult to diagnose. The clinical effects of DILI vary among individuals. However, the outcome determinants remain to be fully established. To the best of our knowledge, the role of anemia in DILI has yet to be reported. The present study reported on the case of one Chinese patient (male; age, 21 years) who experienced obvious drug-induced cholestasis. Of note, the hepatocyte injury was minimal compared with that in previously reported cases treated with the same drug. In addition, the patient suffered from mild hemolytic anemia with no obvious cause. A genetic pedigree analysis revealed compound heterozygous mutations in the congenital anemia-associated gene codanin 1, including the novel rare p.R1067H mutation. Treatment with ursodeoxycholic acid alone sufficed and the outcome was good. Therefore, whilst chronic hemolysis predisposed the liver to cholestasis, it could have shielded the liver from further injuries, since bilirubin, a by-product of hemolysis, is a known antioxidant. The results of the present study indicated that genetic screening may be used for the diagnosis of liver injury concurring with undiagnosed anemia.

PMID:33777192 | PMC:PMC7967802 | DOI:10.3892/etm.2021.9887

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miR-23a-3p regulates the proliferation and apoptosis of human lens epithelial cells by targeting Bcl-2 in an in vitro model of cataracts

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Exp Ther Med. 2021 May;21(5):436. doi: 10.3892/etm.2021.9853. Epub 2021 Feb 26.

ABSTRACT

Cataracts account for ~50% of the cases of blindness in individuals worldwide. The apoptosis of lens epithelial cells (LECs) occurs during the formation of cataracts, which is a non-congenital condition. Numerous microRNAs (miRs) have been reported to regulate apoptosis in LECs. For instance, miR-23a expression levels were shown to be upregulated in cataractous lenses; however, the function of miR-23a in cataracts remains undetermined. To establish an in vitro model of cataracts, human LECs, HLE-B3 cells, were induced with 200 µmol/l H2O2 for 24 h. HLE-B3 cells were transfected with the miR-negative control (NC) mimic, miR-23a-3p mimic, miR-NC inhibitor, miR-23a-3p inhibitor, small interfering RNA (siRNA) targeting BCL2 (siRNA-BCL2) and siRNA-NC. The expression levels of miR-23a-3p were detected using reverse transcrip tion-quantitative PCR. The interaction between miR-23a-3p and the 3'-untranslated region (UTR) of the target mRNA BCL2 was predicted by TargetScan 7.1, and further validated using a dual luciferase reporter assay. The BCL2 protein expression levels were analyzed using western blotting, cell proliferation was determined using a CCK-8 assay and the levels of cell apoptosis were analyzed using flow cytometric analysis. The results of the present study revealed that the expression levels of miR-23a-3p were significantly upregulated, while the expression levels of BCL2 were significantly downregulated in H2O2-induced HLE-B3 cells compared to untreated control cells. BCL2 was shown to be a target of miR-23a-3p. The miR-23a-3p inhibitor subsequently attenuated H2O2-induced apoptosis and increased the proliferation of HLE-B3 cells, which was partially reversed by siRNA-BCL2. In conclusion, the findings of the current study suggested that the inhib ition of miR-23a-3p may attenuate H2O2-induced cataract formation by targeting BCL2, thus providing a novel therapeutic target for the treatment of patients with cataracts in the clinic.

PMID:33777189 | PMC:PMC7967796 | DOI:10.3892/etm.2021.9853

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Dysregulation of lncRNA SNHG1/miR-145 axis affects the biological function of human carotid artery smooth muscle cells as a mechanism of carotid artery restenosis

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Exp Ther Med. 2021 May;21(5):423. doi: 10.3892/etm.2021.9867. Epub 2021 Feb 25.

ABSTRACT

Carotid angioplasty and stenting have developed into reliable options for patients with carotid stenosis. However, postoperative restenosis remains a serious and unresolved problem. Restenosis is partly caused by the proliferation of vascular smooth muscle cells. As certain long non-coding RNAs (lncRNAs) affect cell proliferation and migration, the present study aimed to investigate them as novel biomarkers for restenosis development and to further reveal the potential underlying mechanisms. The expression of lncRNA small nucleolar RNA host gene 1 (SNHG1) and microRNA145 (miR-145) in human carotid artery smooth muscle cells (hHCtASMCs) was analyzed using reverse transcription-quantitative PCR. In addition, a luciferase reporter assay was performed to investigate the interaction between SNHG1 and miR-145. The effects of the SNHG1/miR-145 axis on the proliferation and migration of hHCtASMCs were evaluated by Cell Counting Kit-8 and Transwell assays. Serum SNHG1 and miR-145 expression levels were increased and decreased, respectively, in patients with restenosis (all P<0.001). High SNHG1 and low miR-145 were identified as risk factors for restenosis onset (all P<0.01). Furthermore, decreasing SNHG1 expression levels in hHCtASMCs inhibited cell proliferation and migration. The luciferase reporter assay and expression results demonstrated that miR-145 may be a target of SNHG1 and mediated the effects of SNHG1 on hHCtASMC proliferation and migration. The results obtained suggested that abnormal expression of SNHG1 and miR-145 may be risk factors for restenosis. The present study revealed that the SNHG1/miR-145 axis regulates hHCtASMC proliferation and migration, indicating its potential for restenosis prevention and treatment.

PMID:33777187 | PMC:PMC7967805 | DOI:10.3892/etm.2021.9867

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The Endonasal Endoscopic Management of Cerebrospinal Fluid Rhinorrhea

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Cureus. 2021 Feb 20;13(2):e13457. doi: 10.7759/cureus.13457.

ABSTRACT

Introduction Cerebrospinal fluid (CSF) rhinorrhea is the result of a bony defect at the skull base with disruption of the arachnoid, dura mater, and sinonasal mucosa that leads to an active CSF leak and flow of clear fluid from the nose. The endoscopic repair of CSF leaks and skull defects have been used by an increasing number of surgeons and is the standard of care for repairing CSF leaks. Materials and methods We conducted a retrospective study of all cases of CSF leaks managed via the endonasal endoscopic approach from 2010 to 2020 at a tertiary referral hospital of King Fahad Specialist Hospital, Dammam (KFSH-D). Results Over 10 years, 61 procedures were performed on a total of 56 patients (average age, 39.9 years) with 26 spontaneous CSF leaks and 30 traumatic CSF leaks. The leak sites were frontal bone in 14% of the cases, the roof of the ethmoid in 25%, the cribrifo rm plate of ethmoid in 39%, and the walls of sphenoid sinus in 21%; multiple site defects were found in eight patients. The defect was localized by high-resolution computed tomography (CT) of the paranasal sinuses and skull base and magnetic resonance imaging (MRI) in all patients. CT cisternography, intrathecal fluorescein injection, and topical application of fluorescein dye were used in patients as required. A combination of free grafts and flaps materials were used in most patients. A middle and inferior turbinate graft was used in 12 patients, a septal cartilage graft in 18 patients, and a pedicled nasoseptal flap in 12 patients. The success rate was 92% after the first closure attempt. A recurrence of CSF leaks was observed in four patients. The mean hospitalization time was 6.5 days. The postoperative follow-up period ranged from one year to 10 years with a mean postoperative follow-up time of three years. Conclusions The endonasal endoscopic approach is the current standard of care for repairing most CSF leaks and skull base defects. We have had an excellent experience with endonasal endoscopic CSF leak repair, with high success rates and low morbidity. Our results support the effectiveness and safety of this technique and should encourage otolaryngologists to apply the procedure in cases of CSF leak.

PMID:33777546 | PMC:PMC7984942 | DOI:10.7759/cureus.13457

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Compartmentalization: An Open Technique for Frontal Sinus Repair and Preservation-Description of Technique and Early Case Series

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J Neurol Surg B Skull Base. 2021 Apr;82(2):189-195. doi: 10.1055/s-0039-1696683. Epub 2019 Sep 12.

ABSTRACT

Background Cranialization or obliteration is widely accepted intervention for traumatic or intentional breach of the frontal sinus. These techniques, however, result in the loss of frontal sinus function and have a persistent risk of cerebrospinal fluid (CSF) leak and mucocele. Compartmentalization is an open technique for repair of the frontal sinus using allograft onlay and a vascularized periosteal flap that allows for preservation of frontal sinus function. Objective The main objective of this article is to describe the technique for compartmentalization of the frontal sinus and demonstrate its efficacy and complication rate with an early patient series. Methods Our technique includes the following key components: harvesting of a pedicled periosteal flap, frontal sinus repair through a bifrontal craniotomy with minimal mucosa removal, ensuring the patency of the nasal frontal outflow tract, and separation of the brain from the frontal sinus with a dual layer of periosteum and allograft. All cases of frontal sinus repair using the compartmentalization technique at our institution were reviewed. Charts were reviewed for CSF leak, mucocele, and other complications. Results Twenty-three patients underwent the described frontal sinus repair technique 17 for tumor and 6 for trauma. There were no CSF leaks and no mucoceles. One patient experienced postoperative anemia and a "parameningeal reaction" that were managed with a short course of antibiotics. Conclusions Compartmentalization, due to its sinus preservation and low complication rate, represents a meaningful step forward in neurosurgical technique for open frontal sinus repair. However, long-term outcomes are necessary to fully evaluate risk of mucocele.

PMID:33777633 | PMC:PMC7987381 | DOI:10.1055/s-0039-1696683

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Reconstruct the anterior commissure with intralaryngeal mucosal flap

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Abstract

An anterior glottic web formation occurs from either congenital or acquired causes.1 Acquired anterior glottic web is the most common type of glottic web, and can be caused by surgical, iatrogenic, or external trauma. The severity of clinical symptoms, which include dysphonia or dyspnea, varies significantly according to the extent of the web.2,3 The prevention of glottic web formation is extremely important for surgical intervention on the anterior commissure.

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The Prognostic Variables Affecting the Frontal Sinusotomy Patency Outcome and How to Manage: A Prospective Study

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Abstract

Objectives

The study aimed to assess the factors affecting the frontal sinus patency after endoscopic frontal sinusotomy.

Design

A prospective cohort study

Setting

Tertiary centre hospital

Main outcome measures

Fifty patients with refractory chronic frontal sinusitis (83 operated frontal sinuses) had frontal sinusotomy and followed up for six months. Multiple operative factors were included; the type of the procedure, intraoperative sinus findings, degree of mucosal preservation, and middle turbinate stability. Other factors were also assessed, including smoking, the presence of allergic rhinitis, asthma, gastroesophageal reflux, and other associated medical comorbidities.

Results

The sinus patency success rate was 75.9%. There was a significant difference regarding the intraoperative anteroposterior sinus ostium diameter (5.36 ± 1.45 mm vs 8.88 ± 2.38 mm, p‐value: .001* in the failed group and the success group, respectively). There was a significant association between the patency outcome and the presence of associated medical comorbidities (P‐value: .001*), the presence of allergic rhinitis (P‐value: .001*), the degree of sinus mucosal preservation (P‐value: .012*), and the degree of middle turbinate stability (P‐value: .001*). The multivariate analysis showed that the intraoperative anteroposterior diameter of the sinus ostium, middle turbinate stability, and presence of allergic rhinitis were significant predictors (P‐value: .012*, .042*, and .013*, respectively).

Conclusion

Sinuses with anteroposterior ostium diameters less than 5.36 mm are more susceptible to restenosis. The flail middle turbinate increases the risk of postoperative middle meatus synechia and frontal sinus patency failure. The presence of allergic rhinitis has a negative impact on the patency outcome.

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Intraoperative botulinum toxin injection for superficial partial parotidectomy: A prospective pilot study

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Abstract

Objectives

Sialocele and salivary fistula are not serious but troublesome complications after parotidectomy. Various modalities have been introduced to prevent postoperative saliva‐related complications. However, clinical trials assessing the prophylactic use of botulinum toxin (BTX) for parotidectomy has not been conducted yet. Herein, we report a pilot study investigating the safety and efficacy of intraoperative BTX (iBTX) injection in partial superficial parotidectomy (PSP).

Participants

Patients with benign parotid tumor were prospectively recruited for this clinical trial from 2017 to 2019. The study participants underwent PSP with iBTX injection. We retrospectively reviewed the clinical information of all the consecutive patients who underwent PSP without iBTX from 2013 to 2019. These patients were divided into the two groups: the iBTX group (n = 36) and the control group (n = 54).

Results

Permanent facial palsy was not observed in either group. None had transient marginal palsy in the iBTX group but 2 patients (3.7%) had it in the control group. The incidence of sialocele was significantly lower in the iBTX group than in the control group (2.8% vs. 20.4%, P<0.05). Although the incidence of salivary fistula was lower in the iBTX group than in the control group (0% vs. 7.4%), no significant difference was determined between the two groups (P=0.147). Total drainage volume was significantly lower in the iBTX group than in the control group (55.0ml vs. 116.6ml, P<0.001).

Conclusions

iBTX injection may be safe and effective in reducing sialocele and postoperative drainage in PSP. It might be a useful option to prevent saliva‐related complication after PSP.

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Primary Transoral Robotic Surgery +/‐ Adjuvant Therapy for Oropharyngeal Squamous Cell Carcinoma – a large observational single‐centre series from the United Kingdom

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Abstract

Objectives

To analyse the oncological outcomes following primary Transoral Robotic Surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC).

Design

Observational case series.

Setting

Tertiary centre; first TORS practice to commence in the UK.

Participants

All consecutive patients undergoing primary TORS with curative intent, with or without adjuvant treatment.

Main outcome measures

Descriptive analysis of patient and tumour pathology variables. Survival outcomes: Overall, Disease‐Specific, Progression‐Free, and Locoregional control.

Results

The cohort comprised of 120 patients undergoing TORS with minimum 12 month follow up data and the following characteristics: mean age 58 years, 91 males (76%), 78 tonsil (65%) and 34 base of tongue primaries (28%), 89% HPV related OPSCC. The surgical pathology revealed 14 (12%) with positive margins, 19 (16%) had close margins < 2mm and 31% with extranodal extension.

The treatment was as follows: 39 (33%) treated with TORS alone, 50 (42%) received adjuvant radiotherapy, and 31 (26%) received adjuvant radiotherapy with chemotherapy.

There were 15 recurrences. Estimated survival for all patients at 3 years (95% CI): overall 85% (78‐92), disease‐specific 90% (85‐96), progression‐free 86% (79‐92), locoregional control 90% (84‐96). The equivalent survival figures for the HPV‐related cases alone were: overall 88% (82‐94), disease‐specific 93% (87‐98), progression‐free 88% (81‐95), locoregional control 92% (87‐98).

Conclusions

Whilst TORS has become a common practice in the management of OPSCC in the UK, these are the first reported oncological outcomes. For selected patients, TORS with or without adjuvant therapy is an appropriate treatment modality.

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Nasopharyngeal Carcinoma in Dermatomyositis

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Abstract

The most common cancer associated with dermatomyositis in NPC‐endemic populations is NPC. 90% of dermatomyositis patients with NPC were diagnosed with cancer within a year of myositis onset, whereas the most delayed presentation of NPC occurred 22 months after myositis onset. There was a greater proportion of subclinical early‐stage cancer in NPC associated with dermatomyositis compared to general NPC. Dermatomyositis patients with early‐stage NPC have good survival outcomes while those with advanced‐stage NPC appear to have poorer prognosis compared to general NPC patients. Dermatomyositis patients with anti‐transcription intermediary factor (TIF)‐1ƴ antibodies had a 14.5‐fold higher risk of developing associated cancers compared with seronegative dermatomyositis.

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Role of PD‐1/PD‐L1 inhibitors in the treatment of recurrent/metastatic head and neck squamous cell carcinoma: a systematic review and meta‐analysis

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Abstract

Background

The use of immunotherapy to treat recurrent/metastatic squamous cell carcinoma of the head and neck has become a popular research topic in recent years, and many clinical trials have been carried out.

Objectives

To systematically evaluate the efficacy and safety of PD‐1/PD‐L1 inhibitors in the treatment of recurrent/metastatic head and neck squamous cell carcinoma.

Methods

We searched PubMed, Embase, Cochrane Library and other databases up to 1 November 2019 for publications reporting the use of PD‐1/PD‐L1 inhibitors in the treatment of squamous cell carcinoma of the head and neck. Revman 5.0 was used for combination analysis, and the overall survival (OS), progression‐free survival (PFS), overall response rate (ORR), and adverse events were determined.

Results

Five articles were included. Compared with other treatment methods, this meta‐analysis showed that treatment with PD‐1/PD‐L1 inhibitors can significantly improve OS (P < 0.0001), but there was no significant improvement in PFS or ORR. The risk of anaemia and nausea was significantly reduced by treatment with PD‐1/PD‐L1 inhibitors.

Conclusions and Significance

Treatment with PD‐1/PD‐L1 inhibitors alone can improve the overall survival rate for recurrent/metastatic squamous cell carcinoma of the head and neck but there is no obvious advantage in other aspects and adverse events.

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