Plantar forefoot reconstruction: A proposal of a management algorithm based on a case series analysis: Plantar forefoot reconstruction

xlomafota13 shared this article with you from Inoreader Plantar forefoot reconstruction: A proposal of a management algorithm based on a case series analysis: Plantar forefoot reconstruction Via Journal of plastic, reconstructive & aesthetic surgery : JPRAS J Plast Reconstr Aesthet Surg. 2021 Sep 4:S1748-6815(21)00385-5. doi: 10.1016/j.bjps.2021.08.010. Online ahead of print. ABSTRACT BACKGROUND: Several loco-regional flaps have been described for plantar forefoot coverage. We, herein, report our single-centre experience in plantar forefoot reconstruction and propose a decision-making process based on the defect's size. METHODS: This is a retrospective case series study of all patients who underwent plantar forefoot reconstruction in a 10-year period. We propose a treatment algorithm, based on the defect size. Defects are classified into small, moderate and large. Small defects (<10cm2) can be covered with the hemi-pulp toe flap. Patients with moderate defects (10-25cm2) can be treated with the reverse medial plantar artery flap (MPAF) from the instep area. For large defects (>25cm2), we recommend regional flaps, that is the distally based sura l flap (DBSF) from the ipsilateral calf, or free flaps, such as the anterolateral thigh flap (ALT) or the skin-grafted gracilis flap. RESULTS: The data of 51 patients were collected and analysed. The median age was 58 years (range 19-84). Nine patients had small defects and underwent hemi-pulp toe flap reconstruction. Three patients presented with moderate defects that were covered with reverse MPFs. The vast majority of the patients (39 patients) had large defects. Of these, eight cases were treated with DBSF and 31 cases with free flaps. Free flap transfers were successful in 97% of the cases. Overall complication rate was 25%. CONCLUSION: We conclude that local flaps should be preferred in plantar forefoot reconstruction as they provide like-tissue for small to moderate defects, for large defects regional flaps or free flaps were indicated. A defect-based approach can facilitate the decision-making process. PMID:34649830 | DOI:10.1016/j.bjps.2021.08.010 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

De-escalation strategies in differentiated thyroid cancer

xlomafota13 shared this article with you from Inoreader De-escalation strategies in differentiated thyroid cancer Via Association française pour l'étude du cancer Bull Cancer. 2021 Oct 11:S0007-4551(21)00367-2. doi: 10.1016/j.bulcan.2021.07.008. Online ahead of print. ABSTRACT Thyroid cancer runs the gamut from indolent micropapillary carcinoma to highly aggressive metastatic disease. Today, using prognostic algorithms, treatment and follow-up can be tailored to each patient in order to decrease overtreatment and over-medicalization of indolent disease. Active surveillance of papillary thyroid carcinoma less than 1cm avoids surgery and thyroid hormone replacement in a large proportion of patient whose tumors remain stable for years. Total thyroidectomy, once a dogma in the treatment of all thyroid cancer, is being supplanted by thyroid lobectomy for low-risk cancers, thereby decreasing the surgical risks involved and improving patients' quality of life. Indications for prophylactic central neck dissection, once mandatory, are now being adapted to the risk of cancer recurrence. Radioactive iodine therapy, also previously mandatory for all, is now only employed according to risk factors and expected outcomes. Follow-up is also being tailored to risk factors for recurrence, with less frequent visits and less use of ultrasound and scintigraphy. For more advanced disease, molecular therapies tailored to somatic mutations are opening opportunities for redifferentiation of aggressive tumors which become amenable to radioactive iodine therapy which carries fewer side effects than other systemic therapies. These advances in the management of thyroid cancer with a personalized approach and de-escalation of treatment and follow-up are improving the way we treat thyroid cancer, avoiding overtreatment and improving patients' quality of life. PMID:34649722 | DOI:10.1016/j.bulcan.2021.07.008 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Transvenous embolization of a cerebrospinal fluid-venous fistula for the treatment of spontaneous intracranial hypotension

xlomafota13 shared this article with you from Inoreader Transvenous embolization of a cerebrospinal fluid-venous fistula for the treatment of spontaneous intracranial hypotension Via leak of cerebrospinal fluid J Neurointerv Surg. 2021 Oct 14:neurintsurg-2021-018160. doi: 10.1136/neurintsurg-2021-018160. Online ahead of print. ABSTRACT Cerebrospinal fluid-venous fistula is an increasingly recognized cause of spontaneous intracranial hypotension.1 The site of the leak is between the dural sleeve around a spinal nerve root and the surrounding foraminal veins. In appropriately investigated patients, transvenous embolization of the draining foraminal and paraspinal veins has been shown to be an effective way of treating the disease, with low periprocedural morbidity, improvement in symptoms and radiological appearances.2 Video 1 shows the technique employed in a typical case using Onyx (Medtronic, Minnesota, USA) to embolize a CSF-venous fistula at the right T10 neural foramen.neurintsurg;neurintsurg-2021-018160v1/V1F1V1Video 1. PMID:34649936 | DOI:10.1136/neurintsurg-2021-018160 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Whole-exome sequencing identification of a recurrent CRYBB2 variant in a four-generation Chinese family with congenital nuclear cataracts

xlomafota13 shared this article with you from Inoreader Whole-exome sequencing identification of a recurrent <em>CRYBB2</em> variant in a four-generation Chinese family with congenital nuclear cataracts Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1375. doi: 10.3892/etm.2021.10810. Epub 2021 Sep 28. ABSTRACT Congenital cataracts is the most common cause of visual impairment and blindness in children. Although there have been extensive studies into the pathogenesis of congenital cataracts, the pathogenic mechanism underlying the recurrent variant CRYBB2:c.62T>A(p.I21N) has not been previously reported. Thus, the present study aimed to use whole-exome sequencing (WES) to identify potential genetic variants and investigate how they may have induced the occurrence of cataracts in a four-generation Chinese family with congenital nuclear cataracts. The medical history of this family was recorded and WES was conducted for one proband. Sanger sequencing was used to verify the presence of the putative variant in all participants. PolyPhen-2, SIFT and ProtScale were used to analyze the effect of the identified variants on protein function and hydroph obicity, and Pymol was used to show the structure of the wild-type (Wt) and mutant β-crystallin B2 (CRYBB2) protein. Full-length Wt-CRYBB2 or mutant-CRYBB2 (I21N-CRYBB2) were fused to green fluorescent protein (GFP), and the recombinant plasmids were transfected into HeLa cells. Reverse transcription-quantitative PCR and western blotting were used to detect the expression levels of CRYBB2 mRNA and protein. Immunofluorescence and flow cytometry analyses were used to detect protein localization and apoptosis, respectively. A recurrent variant CRYBB2:c.62T>A(p.I21N) was identified in a four-generation Chinese family with congenital nuclear cataracts. Multiple-sequence alignment of CRYBB2 demonstrated that codon 21 was highly conserved. Pymol revealed that the structure of the I21N-CRYBB2 protein was distinct from that of Wt-CRYBB2. PolyPhen-2 predicted that it had a variant provean score 1.0, suggesting it was 'probably damagi ng', and SIFT predicted it had a variant provean score of -5.113, indicating it was 'deleterious'. ProtScale indicated that the hydrophobicity of the mutation site was significantly reduced. The protein expression levels of the I21N-CRYBB2 were decreased compared with the Wt-CRYBB2. Immunofluorescence analysis revealed that the variant I21N-CRYBB2 protein tended to accumulate around the nucleus, and flow cytometry analysis indicated that it increased cell apoptosis. Furthermore, I21N-CRYBB2 induced the activation of the unfolded protein response (UPR). In conclusion, a pathogenic variant of CRYBB2:c.62T>A(p.I21N) was identified via WES in a four-generation Chinese family with congenital nuclear cataracts. Through biological analysis, it was found that the variant induced abnormal protein aggregation, activated the UPR and triggered excessive cell apoptosis, which may lead to the occurrence of congenital nuclear cataracts in this family. PM ID:34650623 | PMC:PMC8506933 | DOI:10.3892/etm.2021.10810 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

DUSP4 alleviates LPS-induced chondrocyte injury in knee osteoarthritis via the MAPK signaling pathway

xlomafota13 shared this article with you from Inoreader DUSP4 alleviates LPS-induced chondrocyte injury in knee osteoarthritis via the MAPK signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1401. doi: 10.3892/etm.2021.10837. Epub 2021 Oct 1. ABSTRACT Knee osteoarthritis (KOA) is characterized by cartilage damage, and the associated pathogenesis is complex. The expression of dual specificity protein phosphatase 4 (DUSP4) is significantly decreased in osteoarthritis (OA); however, the specific role and mechanism underlying DUSP4 in OA are yet to be elucidated. ATDC5 cells were treated with lipopolysaccharide (LPS) to establish the cell injury model. The expression levels of DUSP4 were decreased in OA chondrocytes, demonstrated by reverse transcription-quantitative PCR and western blot analysis. Following overexpression of DUSP4 by cell transfection, Cell Counting Kit-8, ELISA, TUNEL and western blotting assays were used to detect the cell viability, oxidative stress, inflammation and apoptosis levels of LPS-induced ATDC5 cells. Overexpression of DUSP4 inhibited the activation of the MAPK signali ng pathway, thereby reducing oxidative stress levels, inflammatory response and apoptosis in the OA cell model. The mechanisms underlying DUSP4 in OA were further explored following the addition of MAPK signaling pathway agonist, phorbol 12-myristate 13-acetate (PMA). The addition of PMA reversed the inhibitory effects of DUSP4 overexpression on oxidative stress, inflammatory response and apoptosis in cells. In summary, DUSP4 alleviated LPS-induced chondrocyte injury in KOA via the MAPK signaling pathway. PMID:34650647 | PMC:PMC8506912 | DOI:10.3892/etm.2021.10837 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Peutz-Jeghers syndrome: Skin manifestations and endocrine anomalies (Review)

xlomafota13 shared this article with you from Inoreader Peutz-Jeghers syndrome: Skin manifestations and endocrine anomalies (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1387. doi: 10.3892/etm.2021.10823. Epub 2021 Sep 29. ABSTRACT Peutz-Jeghers syndrome (PJS), a rare autosomal dominant serine/threonine kinase 11 (STK11)/ liver kinase B1 (LKB1) gene-related genodermatosis, is characterized by oral hyperpigmentation (OHP); multiple gastro-intestinal mucosal benign hamartomatous polyps causing local bleeding, occlusion, intussusception, post-resection small bowel syndrome, associated increased risk of small intestinal cancer (incidence during the third decade); and 76% cumulative higher risk than the global population of developing non-gastrointestinal tumors (female predominance) including ovarian/testicular neoplasia, pancreatic and gynecologic (breast, uterus, ovarian) cancers. Suggestive PJS-associated OHP requires STK11 genetic testing. Abdominal pain in an OHP patient may be related to PJS-associated polyps. Other features include focal depigmentation foll owed by hyperpigmentation, and xeroderma pigmentosum-like lesions. The severity of the dermatological findings is correlated with gastrointestinal polyps. The STK11 gene is linked to reserve of primordial follicles, polycystic ovary syndrome, female fertility, and spermatogenesis. PJS is associated with 2 types of ovarian sex-cord stroma tumors (SCSTs): annular tubules (SCTATs) and pure Sertoli cell tumors. SCSTs accounts for 8% of ovarian cancer and SCTATs represents 2% of SCST, which may be associated with the overproduction of progesterone. PJS-SCTAT vs. non-PJS-SCTAT reveals bilateral/multifocal, small tumors with a benign behavior vs. a unique ovarian, large tumor with increased malignant/metastasis risk. Male precocious puberty is due to large cell calcifying Sertoli cell tumors (LCCSCTs). Notably, 30-40% of LCCSCTs are caused by PJS or Carney complex. PJS-LCCSCT is not aggressive, but it may be bilateral/multifocal, with the ultrasound hallmark being micro-calcificatio ns. Testicular, intra-tubular large cell hyalinizing Sertoli cell tumor is the second testicle neoplasia in PJS. The skin and mucosal lesions are useful markers of PJS, assisting with the early identification of hamartomatouspolyps and initiation of serial surveillance of ovarian, or testicular neoplasia. PMID:34650635 | PMC:PMC8506952 | DOI:10.3892/etm.2021.10823< /p> View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Infra-hepatic caval resection en bloc with right nephrectomy followed by caval reconstruction for locally advanced caval leiomyosarcoma: A case report and literature review

xlomafota13 shared this article with you from Inoreader Infra-hepatic caval resection en bloc with right nephrectomy followed by caval reconstruction for locally advanced caval leiomyosarcoma: A case report and literature review Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1377. doi: 10.3892/etm.2021.10812. Epub 2021 Sep 28. ABSTRACT Retroperitoneal sarcomas often require complex surgical procedures in order to achieve complete resection; in such cases both vascular and visceral resections are needed. When it comes to the need for vascular reconstruction, the type of graft as well as the type of reconstructive process are chosen according to the length and location of the resected segment. Meanwhile, depending on the location of the resected segment, other vascular reconstructions may be needed such as the reimplantation of the renal veins. However, in certain cases, this reimplantation is not mandatory, an adequate renal outflow being reported through the collateral network at this level. We present the case of a 43-year-old patient diagnosed with a large retroperitoneal sarcoma originating from the cava vein invading the right kidney. Resection of the tumor was performed en bloc with caval resection and right nephrectomy, without reimplantation of the left renal vein at the level of the graft. Extended visceral and vascular resections might be needed in order to achieve complete resection of inferior cava vein sarcomas; re-implantation of the left renal vein being not mandatory if rich collateral circulation is present. PMID:34650625 | PMC:PMC8506944 | DOI:10.3892/etm.2021.10812 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9

xlomafota13 shared this article with you from Inoreader Euphornin L promotes lipid clearance by dual regulation of LDLR and PCSK9 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1381. doi: 10.3892/etm.2021.10817. Epub 2021 Sep 28. ABSTRACT Our previous study identified euphornin L as an active lipid-lowering compound in high-fat diet-fed Golden Syrian hamsters. The aim of the present study was to investigate the mechanisms underlying the lipid-lowering effects of euphornin L. Euphornin L in HepG2 cells was assessed via DiI-LDL update assays and found to increase LDL-update and LDLR protein levels. RNA interference assays demonstrated that its LDL-update effects were LDLR-dependent. Dual luciferase reporter and mRNA stability assays revealed that euphornin L had little effect on LDLR mRNA transcription but lengthened the half-life of LDLR mRNA by activating ERK protein in cells. Euphornin L decreased the secretion of PCSK9 protein and alleviated PCSK9-mediated LDLR protein degradation. In vivo experiments in hamsters, which were treated with euphornin L (30 mg/k g/day) for 3 weeks, confirmed these findings. LDLR protein levels in liver tissue were upregulated, while PCSK9 protein levels in serum were downregulated. Altogether, the present study demonstrated that euphornin L increased LDLR protein levels by dual regulation of LDLR mRNA and PCSK9 protein, and represented an active compound for lipid-lowering drug development. PMID:34650629 | PMC:PMC8506954 | DOI:10.3892/etm.2021.10817 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Monensin suppresses cell proliferation and invasion in ovarian cancer by enhancing MEK1 SUMOylation

xlomafota13 shared this article with you from Inoreader Monensin suppresses cell proliferation and invasion in ovarian cancer by enhancing MEK1 SUMOylation Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1390. doi: 10.3892/etm.2021.10826. Epub 2021 Sep 30. ABSTRACT Ovarian cancer is the most lethal gynecologic malignancy, and is usually diagnosed at an advanced stage. Most patients relapse within 12-24 months and die from progressive chemotherapy-resistant diseases. Significant progress has been made in developing new targeted therapies for human cancer, including ovarian cancer. However, an effective alternative to drug development is to repurpose drugs. The present study investigated the possibility of reusing the antibiotic monensin as an anti-ovarian cancer drug. After applying a series of titrated monensin on a panel of ovarian cancer cell lines, the growth, migration and invasion of cells were explored. Multiple signaling molecules associated with epithelial-to-mesenchymal transition were also regulated by monensin. The mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway was further found to be the key regulator affected by monensin. Additionally, monensin enhanced the MEK1 SUMOylation in vitro and in vivo, and the SUMOylation degree depended on time and dose. Xenograft studies verified that monensin effectively inhibited xenograft tumor growth by increasing the SUMOylation of MEK1. The aforementioned results suggested that monensin is a good candidate for anti-ovarian cancer by enhancing MEK1 SUMOylation and inhibiting the MEK-ERK pathway. PMID:34650638 | PMC:PMC8506924 | DOI:10.3892/etm.2021.10826 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical and surgical algorithm for managing iatrogenic bile duct injuries during laparoscopic cholecystectomy: A multicenter study

xlomafota13 shared this article with you from Inoreader Clinical and surgical algorithm for managing iatrogenic bile duct injuries during laparoscopic cholecystectomy: A multicenter study Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1385. doi: 10.3892/etm.2021.10821. Epub 2021 Sep 29. ABSTRACT The present study was a multicenter, analytical, nonrandomized research on 108 cases of intraoperative vascular and bile duct lesions during laparoscopic cholecystectomies. We selected these cases from 16,559 cholecystectomies performed entirely laparoscopically or debuted laparoscopically and converted to an open approach. The study included two surgical centers labeled as primary, with extensive experience in hepato-biliary reconstructive surgery, and four other centers labeled as secondary that referred cases to the previous two. Our study analyzed several key parameters such as the percentage of iatrogenic lesions recorded, the variability of the main biliary pathway and conformation as well as its relationship to the adjacent critical anatomical landmarks, the anatomical and physiopathological characteristics of pathology requiring surgical intervention, factors related to laparoscopic surgical technique, the surgical technique used to repair the recorded lesions, the duration of survivability and the rate of the occurring complications. Based on the analysis of these parameters, we developed a descriptive algorithm with visual representation relying on several decisional points to guide the surgeons in choosing the optimal treatment method so that patients will benefit from a favorable clinical path. PMID:34650633 | PMC:PMC8506945 | DOI:10.3892/etm.2021.10821 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Melatonin attenuates low shear stress-induced pyroptosis and endothelial cell dysfunction via the RORα/miR-223/STAT-3 signalling pathway

xlomafota13 shared this article with you from Inoreader Melatonin attenuates low shear stress-induced pyroptosis and endothelial cell dysfunction via the RORα/miR-223/STAT-3 signalling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Dec;22(6):1392. doi: 10.3892/etm.2021.10828. Epub 2021 Sep 30. ABSTRACT Endothelial cells sense changes in blood flow shear stress and affect the progression of atherosclerotic plaques. Pyroptosis is an inflammatory form of cell death and has been implicated in cardiovascular diseases. Melatonin and its nuclear receptor retinoid-related orphan receptor α (RORα) have protective effects on the development of atherosclerosis. To date, whether melatonin can prevent endothelial cell pyroptosis and dysfunction in pathological shear stress remains unclear. In the present study, human umbilical vein endothelial cells (ECs) were cultured under low shear stress conditions (5 dyne/cm2) for 24 h and treated with or without melatonin (2 µmol/l). The binding sites of the microRNA (miR)-223 promoter and RORα were predicted using the JASPAR website. Expression of pyroptosis-related proteins, including cleaved N-termin al gasdermin D, caspase-1, intercellular adhesion molecule 1 (ICAM-1) and nitric oxide (NO) were assessed. The results indicated that low shear stress increased pyroptosis and ICAM-1 expression, whereas it decreased NO levels. Melatonin alleviated pyroptosis and ICAM-1 expression and increased the production of NO in ECs. Further assessment revealed that low-level shear stress decreased RORα protein and mRNA expression, whereas melatonin would bind to RORα and thereby promoted miR-223 transcription in ECs. The present study also identified signal transducer and activator of transcription 3 (STAT-3) as a potential target gene of miR-223-3p. When transfected with miR-223 inhibitor, ECs up-regulated the expression of pyroptosis-related proteins and ICAM-1, and down-regulated NO levels. By contrast, silencing STAT-3 expression diminished the protective effect of miR-223. These results indicated that melatonin prevented ECs from undergoing pyroptosis and alleviated dysfunction via the RORα/miR-223/STAT-3 signalling pathway. This information could aid in the development of novel therapeutic approaches and provide new insights into atherosclerosis. PMID:34650640 | PMC:PMC8506941 | DOI:10.3892/etm.2021.10828 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.