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1.
Cureus ; 16(6): e61736, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975534

ABSTRACT

BACKGROUND:  To describe the surgical technique of non-compressive intramedullary threaded nail (IMTN) fixation of distal ulnar neck fractures and present the clinical and radiographic outcomes of four patients treated with this novel technique. METHODS: At a single Level 1 Trauma Center, a retrospective review was conducted for patients with distal ulnar neck fractures treated with retrograde IMTN between 2022 and 2024. Exclusion criteria included inadequate follow-up. A single surgeon performed all procedures using percutaneous retrograde IMTN fixation through the central disc of the triangular fibrocartilage complex (TFCC). Patients initiated a range of motion (ROM) protocol two weeks post-operatively. Post-operative radiographic images were used to calculate the ratio of IMTN diameter to the distal ulnar medullary isthmus diameter proximal to the fracture site. Radiographic changes in displacement, angulation, and ulnar variance were calculated between the first and last follow-up radiographs. Functional outcomes including grip strength and ROM were collected. RESULTS: Four patients with distal ulnar neck fractures were treated with retrograde IMTN between 2022 and 2024. They were followed for a minimum of three months post-operatively. All were female with an average age of 65 years. All distal ulna fractures were associated with operatively treated intraarticular distal radius fractures. All patients were treated with 75 mm length and 4.5 mm diameter IMTNs. IMTN-to-Isthmus ratio was greater than 60% in all cases. Average radiographic displacement and angulation were unchanged at the final follow-up. The average ulnar variance increased by 1.2 mm. At the final follow-up, there were no post-operative complications. No cases demonstrated ulnar-sided wrist pain, nonunion, or required revision surgery. CONCLUSIONS: Retrograde IMTN fixation is a novel surgical technique for the treatment of distal ulnar neck fractures. We found limited but promising post-operative radiographic and functional outcomes in our patients without reported ulnar-sided wrist pain, nonunion, or need for hardware removal.

2.
PLoS Negl Trop Dis ; 18(5): e0012213, 2024 May.
Article in English | MEDLINE | ID: mdl-38787898

ABSTRACT

BACKGROUND: Despite several years of LF-MDA implementation, Ghana still has some districts with mf prevalence >1%, partly due to poor treatment coverage levels resulting from non-participation in MDA. To address the challenges, we implemented Engage & Treat (E&T) and Test & Treat (T&T) strategies for individuals who miss or refuse MDA respectively, in a hotspot district, enabling us to reach many of those who seldom, or never, take part in MDA. This financial cost study was undertaken to analyse data on the LF-MDA, E&T and T&T implementation in 2021 and the financial cost to inform the rollout of the E&T and T&T as mop-up strategies in future LF-MDAs. METHODS: This costing study analysed cost data from the 2021 LF-MDA implementation activities carried out by the Neglected Tropical Diseases (NTD) programme of the Ghana Health Service and the SENTINEL study, carried out in Ahanta West district for the two interventions (i.e., E&T and T&T). The 2021 Ghana Population and Housing Census data was used to estimate the LF-MDA-eligible population. The financial cost per person treated was estimated and these costs were applied to the projected population to obtain the financial cost for subsequent years. RESULTS: Implementing MDA mop-up strategies either through the E&T or T&T to improve coverage comes at an additional cost to the elimination goals. For example, in 2024 the projected cost per person treated by the routine LF-MDA is estimated at US$0.83. The cost using the integrated LF-MDA and the E&T, T&T led by the NTD programme or T&T integrated into the health system was estimated at US$1.62, US$2.88, and US$2.33, respectively, for the same year. Despite the increased cost, the proposed combined LF-MDA and mop-up strategies will have a higher estimated population treated for 2024 (i.e., 1,392,211) compared to the routine LF-MDA approach (i.e., 988,470) for the same year. CONCLUSION: Combining LF-MDA with E&T/T&T mop-up strategies, despite their high costs, may provide NTD Programmes with the options of improving treatment coverage and reaching the LF elimination target sooner, given that the routine LF-MDA alone approach has been implemented for many years with some districts yet to reach the elimination targets.


Subject(s)
Disease Eradication , Elephantiasis, Filarial , Ghana/epidemiology , Humans , Elephantiasis, Filarial/economics , Elephantiasis, Filarial/prevention & control , Elephantiasis, Filarial/epidemiology , Disease Eradication/economics , Disease Eradication/methods , Mass Drug Administration/economics , Filaricides/therapeutic use , Filaricides/economics , Prevalence
3.
Clin Cancer Res ; 26(11): 2535-2545, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32086345

ABSTRACT

PURPOSE: Most ALK-positive lung cancers will develop ALK-independent resistance after treatment with next-generation ALK inhibitors. MET amplification has been described in patients progressing on ALK inhibitors, but frequency of this event has not been comprehensively assessed. EXPERIMENTAL DESIGN: We performed FISH and/or next-generation sequencing on 207 posttreatment tissue (n = 101) or plasma (n = 106) specimens from patients with ALK-positive lung cancer to detect MET genetic alterations. We evaluated ALK inhibitor sensitivity in cell lines with MET alterations and assessed antitumor activity of ALK/MET blockade in ALK-positive cell lines and 2 patients with MET-driven resistance. RESULTS: MET amplification was detected in 15% of tumor biopsies from patients relapsing on next-generation ALK inhibitors, including 12% and 22% of biopsies from patients progressing on second-generation inhibitors or lorlatinib, respectively. Patients treated with a second-generation ALK inhibitor in the first-line setting were more likely to develop MET amplification than those who had received next-generation ALK inhibitors after crizotinib (P = 0.019). Two tumor specimens harbored an identical ST7-MET rearrangement, one of which had concurrent MET amplification. Expressing ST7-MET in the sensitive H3122 ALK-positive cell line induced resistance to ALK inhibitors that was reversed with dual ALK/MET inhibition. MET inhibition resensitized a patient-derived cell line harboring both ST7-MET and MET amplification to ALK inhibitors. Two patients with ALK-positive lung cancer and acquired MET alterations achieved rapid responses to ALK/MET combination therapy. CONCLUSIONS: Treatment with next-generation ALK inhibitors, particularly in the first-line setting, may lead to MET-driven resistance. Patients with acquired MET alterations may derive clinical benefit from therapies that target both ALK and MET.


Subject(s)
Anaplastic Lymphoma Kinase/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Drug Resistance, Neoplasm/genetics , Gene Amplification , Lung Neoplasms/genetics , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-met/genetics , Aminopyridines , Anaplastic Lymphoma Kinase/genetics , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Crizotinib/pharmacology , Gene Expression Regulation, Neoplastic , High-Throughput Nucleotide Sequencing , Humans , Lactams , Lactams, Macrocyclic/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Prognosis , Pyrazoles , Tumor Cells, Cultured
4.
Int J Surg ; 75: 84-90, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32014598

ABSTRACT

INTRODUCTION: Direct-acting antivirals (DAA's) have revolutionized hepatitis-C virus (HCV) treatment, however controversy remains regarding timing of treatment in relation to liver-transplant (LT). METHODS: Single-center retrospective study assessing outcomes of listed HCV positive patients in the DAA-era (2014-2017). Patients treated with DAA's before LT (DAA pre-LT) were compared to those who were not treated before LT (No DAA pre-LT) RESULTS: 156 HCV positive patients were listed during study-period; 104 (67%) underwent LT while 52 (33%) were de-listed. Of transplanted patients, 48 (46%) received DAA pre-LT while 56 (54%) were treated post-LT. Both groups were comparable in age, gender, MELD, patient and graft survival and cure-rates (98% in DAA pre-LTvs.95% in No DAA pre-LT; p > 0.05). DAA pre-LT group required higher number of treatments-per-patient to clear virus (1.46vs.1.06; p = 0.0006), spent more time on waitlist (331d.vs150d; p = 0.0040) and were less likely to receive livers from HCV positive donors (6%vs.25%; p = 0.0148). Twenty-nine (56%) of the 52 delisted received DAA. They had lower listing-MELD (12vs.18; p = 0.0033), and were more likely to be delisted for "condition improved" (34%vs.4%; p = 0.0143) compared to the 23 (44%) delisted patients who did not receive DAA's. CONCLUSIONS: DAA's were equally effective in clearing HCV in listed patients irrespective of timing. DAA pre-LT can disadvantage some patients through increase number of treatments needed and longer waitlist times, but treatment in some listed patients with low-MELD can improve condition and alleviate need for LT.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C/surgery , Liver Transplantation , Aged , Female , Hepatitis C/drug therapy , Humans , Liver Transplantation/mortality , Male , Middle Aged , Retrospective Studies , Waiting Lists
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