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1.
Bone Joint J ; 106-B(9): 986-993, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39216845

RESUMO

Aims: The aim of this study was to compare the early postoperative mortality and morbidity in older patients with a fracture of the femoral neck, between those who underwent total hip arthroplasty (THA) and those who underwent hemiarthroplasty. Methods: This nationwide, retrospective cohort study used data from the Japanese Diagnosis Procedure Combination database. We included older patients (aged ≥ 60 years) who underwent THA or hemiarthroplasty after a femoral neck fracture, between July 2010 and March 2022. A total of 165,123 patients were included. The THA group was younger (mean age 72.6 (SD 8.0) vs 80.7 years (SD 8.1)) and had fewer comorbidities than the hemiarthroplasty group. Patients with dementia or malignancy were excluded because they seldom undergo THA. The primary outcome measures were mortality and complications while in hospital, and secondary outcomes were readmission and reoperation within one and two years after discharge, and the costs of hospitalization. We conducted an instrumental variable analysis (IVA) using differential distance as a variable. Results: The IVA analysis showed that the THA group had a significantly higher rate of complications while in hospital (risk difference 6.3% (95% CI 2.0 to 10.6); p = 0.004) than the hemiarthroplasty group, but there was no significant difference in the rate of mortality while in hospital (risk difference 0.3% (95% CI -1.7 to 2.2); p = 0.774). There was no significant difference in the rate of readmission (within one year: risk difference 1.3% (95% CI -1.9 to 4.5); p = 0.443; within two years: risk difference 0.1% (95% CI -3.2 to 3.4); p = 0.950) and reoperation (within one year: risk difference 0.3% (95% CI -0.6 to 1.1); p = 0.557; within two years: risk difference 0.1% (95% CI -0.4 to 0.7); p = 0.632) after discharge. The costs of hospitalization were significantly higher in the THA group than in the hemiarthroplasty group (difference $2,634 (95% CI $2,496 to $2,772); p < 0.001). Conclusion: Among older patients undergoing surgery for a femoral neck fracture, the risk of early complications was higher after THA than after hemiarthroplasty. Our findings should aid in clinical decision-making in these patients.


Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral , Hemiartroplastia , Complicações Pós-Operatórias , Humanos , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia/efeitos adversos , Hemiartroplastia/métodos , Artroplastia de Quadril/métodos , Artroplastia de Quadril/efeitos adversos , Idoso , Masculino , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Reoperação/estatística & dados numéricos , Japão/epidemiologia , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos
2.
Bone Joint J ; 106-B(8): 849-857, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39084654

RESUMO

Aims: The use of multimodal non-opioid analgesia in hip fractures, specifically acetaminophen combined with non-steroidal anti-inflammatory drugs (NSAIDs), has been increasing. However, the effectiveness and safety of this approach remain unclear. This study aimed to compare postoperative outcomes among patients with hip fractures who preoperatively received either acetaminophen combined with NSAIDs, NSAIDs alone, or acetaminophen alone. Methods: This nationwide retrospective cohort study used data from the Diagnosis Procedure Combination database. We included patients aged ≥ 18 years who underwent surgery for hip fractures and received acetaminophen combined with NSAIDs (combination group), NSAIDs alone (NSAIDs group), or acetaminophen alone (acetaminophen group) preoperatively, between April 2010 and March 2022. Primary outcomes were in-hospital mortality and complications. Secondary outcomes were opioid use postoperatively; readmission within 90 days, one year, and two years; and total hospitalization costs. We used propensity score overlap weighting models, with the acetaminophen group as the reference group. Results: We identified 93,018 eligible patients, including 13,068 in the combination group, 29,203 in the NSAIDs group, and 50,474 in the acetaminophen group. Propensity score overlap weighting successfully balanced patient characteristics among the three groups, with no significant difference in in-hospital mortality rates observed among the groups (combination group risk difference 0.0% (95% CI -0.5 to 0.4%); NSAIDs group risk difference -0.2% (95% CI -0.5 to 0.2%)). However, the combination group exhibited a significantly lower risk of in-hospital complications than the acetaminophen group (risk difference -1.9% (95% CI -3.2 to -0.6%)) as well as a significantly lower risk of deep vein thrombosis (risk difference -1.4% (95% CI -2.2 to -0.7%)). Furthermore, total hospitalization costs were higher in the NSAIDs group than in the acetaminophen group (difference USD $438 (95% CI 249 to 630); p < 0.001). No significant differences in other secondary outcomes were observed among the three groups. Conclusion: The combination of acetaminophen with NSAIDs appears to be safe and advantageous in terms of reducing in-hospital complications.


Assuntos
Acetaminofen , Analgésicos não Narcóticos , Anti-Inflamatórios não Esteroides , Quimioterapia Combinada , Fraturas do Quadril , Mortalidade Hospitalar , Humanos , Acetaminofen/uso terapêutico , Feminino , Anti-Inflamatórios não Esteroides/uso terapêutico , Masculino , Fraturas do Quadril/cirurgia , Idoso , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Analgésicos não Narcóticos/uso terapêutico , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão
4.
J Orthop Sci ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38342711

RESUMO

BACKGROUND: Periprosthetic bone loss following total hip arthroplasty (THA) threatens prosthesis stability. This systematic review and network meta-analysis aimed to compare the efficacy of anti-osteoporotic drugs for measures of hip function according to functional outcomes, periprosthetic femoral bone mineral density loss in each Gruen zone, and revision surgery after THA. METHODS: The systematic search of six literature databases was conducted in December 2021 in accordance with PRISMA guidelines. Adult participants who underwent primary THA were included. A random-effects network meta-analysis was performed within a frequentist framework, and the confidence in the evidence for each outcome was evaluated using the CINeMA tool, which assessed the credibility of results from the network meta-analysis. We included 22 randomized controlled trials (1243 participants) comparing the efficacy and safety of bisphosphonates (including etidronate, clodronate, alendronate, risedronate, pamidronate, and zoledronate), denosumab, selective estrogen receptor modulator, teriparatide, calcium + vitamin D, calcium, and vitamin D. We defined the period for revision surgery as the final follow-up period. RESULTS: Raloxifene, bisphosphonate, calcium + vitamin D, and denosumab for prosthetic hip function might have minimal differences when compared with placebos. The magnitude of the anti-osteoporotic drug effect on periprosthetic femoral bone loss varied across different Gruen zones. Bisphosphonate, denosumab, teriparatide might be more effective than placebo in Gruen zone 1 at 12 months after THA. Additionally, bisphosphonate might be more effective than placebo in Gruen zones 2, 5, 6, and 7 at 12 months after THA. Denosumab was efficacious in preventing bone loss in Gruen zones 6 and 7 at 12 months after THA. Teriparatide was likely to be efficacious in preventing bone loss in Gruen zone 7 at 12 months after THA. Raloxifene was slightly efficacious in preventing bone loss in Gruen zones 2 and 3 at 12 months after THA. Calcium was slightly efficacious in preventing bone loss in Gruen zone 5 at 12 months after THA. None of the studies reported revision surgery. CONCLUSIONS: Bisphosphonate and denosumab may be effective anti-osteoporotic drugs for preventing periprosthetic proximal femoral bone loss due to stress shielding after THA, particularly in cementless proximal fixation stems, which are the most commonly used prostheses worldwide.

5.
Intern Med ; 63(6): 867-871, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37495530

RESUMO

A 58-year-old woman with rheumatoid arthritis was diagnosed with methotrexate-associated Hodgkin lymphoma. After receiving several chemotherapy regimens, she started nivolumab treatment. Two weeks later, she was hospitalized with worsening finger, wrist, and elbow joint pain. A synovial biopsy of the wrist joint showed villous synovial proliferation and linear infiltration of CD68-/CD3-positive T cells (with more CD8 than CD4 T cells) but no CD20-positive B cells or CD138-positive macrophages. These findings corresponded to synovitis associated with immune-related adverse events, which are induced mainly by T cells and are different from typical rheumatoid arthritis (RA), in which B cells play a central role.


Assuntos
Artrite Reumatoide , Sinovite , Feminino , Humanos , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Artralgia , Artrite Reumatoide/tratamento farmacológico , Linfócitos B , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico
6.
J Antibiot (Tokyo) ; 76(12): 691-698, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37758819

RESUMO

Pseudomonas aeruginosa is one of the most concerning pathogenic bacteria. We screened antibiotics using a highly drug-sensitive P. aeruginosa strain and an oligotrophic medium, and successfully isolated novel antibiotics, namely cycloimidamicins (CIMs), from a rare actinomycete strain, Lentzea sp. MM249-143F7. X-ray and nuclear magnetic resonance analyses revealed that CIMs possess a distinctive and unprecedented molecular structure, containing tetramic acid and an imidazole ring bound directly to indolone. The CIMs exhibited potent antibacterial activity against Gram-negative bacteria, as well as translation inhibition in Escherichia coli in both intact cells and in vitro. Additionally, E. coli strains resistant to known translation inhibitors did not exhibit cross-resistance to CIMs, suggesting that CIMs inhibit bacterial growth by blocking translation through a novel mechanism.


Assuntos
Escherichia coli , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana
7.
Antimicrob Agents Chemother ; 67(7): e0160622, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37314349

RESUMO

The increasing burden and spread of resistant malaria parasites remains an immense burden to public health. These factors have driven the demand to search for a new therapeutic agent. From our screening, phebestin stood out with nanomolar efficacy against Plasmodium falciparum 3D7. Phebestin was initially identified as an aminopeptidase N inhibitor. Phebestin inhibited the in vitro multiplication of the P. falciparum 3D7 (chloroquine-sensitive) and K1 (chloroquine-resistant) strains at IC50 values of 157.90 ± 6.26 nM and 268.17 ± 67.59 nM, respectively. Furthermore, phebestin exhibited no cytotoxic against human foreskin fibroblast cells at 2.5 mM. In the stage-specific assay, phebestin inhibited all parasite stages at 100 and 10-fold its IC50 concentration. Using 72-h in vitro exposure of phebestin at concentrations of 1 µM on P. falciparum 3D7 distorted the parasite morphology, showed dying signs, shrank, and prevented reinvasion of RBCs, even after the compound was washed from the culture. An in silico study found that phebestin binds to P. falciparum M1 alanyl aminopeptidase (PfM1AAP) and M17 leucyl aminopeptidase (PfM17LAP), as observed for bestatin. In vivo evaluation using P. yoelii 17XNL-infected mice with administrations of 20 mg/kg phebestin, once daily for 7 days, resulted in significantly lower parasitemia peaks in the phebestin-treated group (19.53%) than in the untreated group (29.55%). At the same dose and treatment, P. berghei ANKA-infected mice showed reduced parasitemia levels and improved survival compared to untreated mice. These results indicate that phebestin is a promising candidate for development as a potential therapeutic agent against malaria.


Assuntos
Antimaláricos , Malária Falciparum , Malária , Humanos , Animais , Camundongos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Aminopeptidases/uso terapêutico , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Cloroquina/farmacologia , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum , Plasmodium berghei
8.
J Antibiot (Tokyo) ; 75(10): 535-541, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36071214

RESUMO

In the course of our screening program for new anti-methicillin-resistant Staphylococcus aureus antibiotics, four novel antibiotics, termed wychimicins A-D, were isolated from the culture broth of the rare actinomycete Actinocrispum wychmicini strain MI503-AF4. Wychimicins are spirotetronates possessing a macrocyclic 13-membered ring containing trans-decalin and ß-D-xylo-hexopyranose moieties connected to C-17 by an O-glycosidic linkage according to MS, NMR and X-ray analyses. In X-ray crystal structure analysis, the Flack constant was 0.10 (11). The stereochemistry of the spirocarbon C-25 was R. Wychimicins had a minimum inhibitory concentration of 0.125-2 µg ml-1 against methicillin-resistant Staphylococcus aureus.


Assuntos
Actinobacteria , Actinomycetales , Staphylococcus aureus Resistente à Meticilina , Policetídeos , Antibacterianos/química , Testes de Sensibilidade Microbiana
9.
Spine (Phila Pa 1976) ; 47(17): 1227-1233, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35797444

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To develop and evaluate a new grading system for destructive lumbar spondyloarthropathy (DLSA) by assessing bony destruction of the facet joints; to evaluate interrater reliability; and to determine the association between anteroposterior (AP) dural sac diameter at the lumbar level and the new grading. SUMMARY OF BACKGROUND DATA: The characteristics of DLSA are unknown, hindering clinical care and research. Imaging to determine the cause of DLSA may positively contribute to patient outcome or well-being by providing prognostic information. PATIENTS AND METHODS: In the magnetic resonance images (MRIs), we measured an axial midline AP dural sac diameter and evaluated bone destruction caused by amyloidosis at the level of the center of each lumbar disk of the lumbar spine. Two orthopedic surgeons independently evaluated each case at two-month intervals and assigned the grade by rating bone destruction at each lumbar level. Weighted κ and intraclass correlation coefficients for interrater reliability were calculated. In addition, the correlation between the AP diameter of the spinal dural sac at the lumbar level and the new MRI-based DLSA grade was examined. RESULTS: The sample size of 82 patients was reached by examining records of 118 consecutive patients. The mean (SD) age of the included patients was 65 (7.2) years, and 36 (43.9%) were women. The grading of DLSA showed moderate to good interrater reliability at both assessments (κ, 0.59-0.78). Intraclass correlation coefficient showed substantial to excellent agreement (intraclass correlation coefficient, 0.63-0.86). The AP diameter of the spinal dural sac at the lumbar level showed a significant correlation with the new grading ( P <0.001). CONCLUSIONS: The new MRI-based grading system for DLSA has good interrater reliability, although the strength of agreement varies somewhat. The new grading system correlates with AP dural sac diameter. Thus, this classification focused on facet erosion, which leads to functional incompetence may be helpful in surgical decision-making.


Assuntos
Estenose Espinal , Espondiloartropatias , Articulação Zigapofisária , Idoso , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Espondiloartropatias/diagnóstico por imagem , Articulação Zigapofisária/diagnóstico por imagem
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