Novel therapeutic interventions towards improved management of septic arthritis

AbstractSeptic arthritis (SA) represents a medical emergency that needs immediate diagnosis and urgent treatment. Despite aggressive treatment and rapid diagnosis of the causative agent, the mortality and lifelong disability, associated with septic arthritis remain high as close to 11%. Moreover, with the rise in drug resistance, the rates of failure of conventional antibiotic therapy have also increased. Among the etiological agents frequently isolated from cases of septic arthritis, Staphylococcus aureus emerges as a dominating pathogen, and to worsen, the rise in methicillin-resistant S. aureus (MRSA) isolates in bone and joint infections is worrisome. MRSA associated cases of septic arthritis exhibit higher mortality, longer hospital stay, and higher treatment failure with poorer clinical outcomes as compared to cases caused by the sensitive strain i.e methicillin-sensitive S. aureus (MSSA).In addition to this, equal or even greater damage is imposed by the exacerbated immune response mounted by the patient’s body in a futile attempt to eradicate the bacteria. The antibiotic therapy may not be sufficient enough to control the progression of damage to the joint involved thus, adding to higher mortality and disability rates despite the prompt and timely start of treatment. This situation implies that efforts and focus towards studying/understanding new strategies for improved management of sepsis arthritis is prudent and worth exploring.The review article aims to give a complete insight into the new therapeutic approaches studied by workers lately in this field. To the best of our knowledge studies highlighting the novel therapeutic strategies against septic arthritis are limited in the literature, although articles on pathogenic mechanism and choice of antibiotics for therapy, current treatment algorithms followed have been discussed by workers in the past. The present study presents and discusses the new alternative approaches, their mechanism of action, proof of concept, and work done so far towards their clinical success. This will surely help to enlighten the researchers with comprehensive knowledge of the new interventions that can be used as an adjunct therapy along with conventional treatment protocol for improved success rates.

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Short-course antibiotic treatment of bone and joint infections in children: a retrospective study at Montpellier University Hospital from 2009 to 2013

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz358 ◽

2019 ◽

Vol 74 (12) ◽

pp. 3579-3587 ◽

Cited By ~ 2

Author(s):

A Filleron ◽

M E Laurens ◽

G Marin ◽

H Marchandin ◽

O Prodhomme ◽

...

Keyword(s):

Retrospective Study ◽

Antibiotic Therapy ◽

Septic Arthritis ◽

Treatment Duration ◽

University Hospital ◽

Short Term ◽

Joint Infections ◽

Intravenous Treatment ◽

Short Course ◽

Prolonged Antibiotic Therapy

Abstract Background Acute haematogenous bone and joint infections (AHBJI) represent a diagnostic and therapeutic emergency in children, with significant potential sequelae in the case of delayed treatment. Although historically the recommendations for treatment have been based on surgery and prolonged antibiotic therapy, recent studies have demonstrated that short-course antibiotic therapy is also effective. Objectives We evaluated a short-term antibiotic protocol for both osteomyelitis and septic arthritis in a 6 year retrospective study at the University Hospital of Montpellier. Methods This protocol was based on an initial intravenous treatment with a re-evaluation after 48 h and an early switch to oral therapy in the case of a favourable clinical course for a minimum total duration of 15 days. Antibiotics were selected based on local microbiological epidemiology and systematically adapted to bacteriological results. Results One hundred and seventy-six cases of AHBJI were included, comprising 56 patients with osteomyelitis, 95 with septic arthritis and 25 who had both of these. The aetiological agent was identified in 42% of the cases, with the main pathogens being Staphylococcus aureus (39%) and Kingella kingae (27%). The mean intravenous treatment duration was 4 days, while the total treatment duration was 15 days. There were no treatment failures, mild sequelae occurred in 1% of the cases and the secondary surgical revision rate was 7%. Conclusions The results of this study are comparable to those reported for evaluations of prolonged antibiotic therapy protocols, thus indicating that a common short-term antimicrobial therapy for the management of both osteomyelitis and septic arthritis (minimum of 15 days) is a viable option for treating AHBJI in children. Further prospective studies to confirm these findings are hence warranted.

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Acute Septic Arthritis

Clinical Microbiology Reviews ◽

10.1128/cmr.15.4.527-544.2002 ◽

2002 ◽

Vol 15 (4) ◽

pp. 527-544 ◽

Cited By ~ 312

Author(s):

Mark E. Shirtliff ◽

Jon T. Mader

Keyword(s):

Septic Arthritis ◽

Antimicrobial Therapy ◽

Bacterial Species ◽

Good Prognosis ◽

Medical Emergency ◽

Laboratory Findings ◽

Mortality And Morbidity ◽

Joint Infections ◽

Prosthetic Joint Infections ◽

Focus Of Infection

SUMMARY Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection.

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Linezolid versus daptomycin treatment for periprosthetic joint infections: a retrospective cohort study

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-019-1375-7 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Masahiro Sawada ◽

Kenichi Oe ◽

Masayuki Hirata ◽

Hiroshi Kawamura ◽

Narumi Ueda ◽

...

Keyword(s):

Infection Control ◽

Adverse Reactions ◽

Treatment Effectiveness ◽

Clinical Success ◽

Implant Removal ◽

Success Rates ◽

Gram Positive ◽

Joint Infections ◽

Implant Retention ◽

Group D

Abstract Background Linezolid (LZD) and daptomycin (DAP) are predominantly used to target gram-positive pathogens; however, treatment effectiveness and adverse reactions for periprosthetic joint infections (PJIs) remain unknown. The aim of this study was to compare the effectiveness and adverse reactions of LZD and DAP for PJIs. Methods This study retrospectively evaluated 82 patients between June 2009 and December 2017, to compare the effectiveness of LZD (group L, n = 39) and DAP (group D, n = 43) for treatment of PJIs harboring gram-positive microorganisms. Surgical options used with LZD or DAP therapy included implant retention, implant removal, and a shift to another appropriate antibiotic. Infection control was defined as not requiring implant removal after the final treatment. Results Gram-positive pathogens were isolated from 72% of group L and 70% of group D patients, respectively. Whole infection control rates against gram-positive pathogens in groups L and D were 79% and 77%, respectively. Furthermore, infection control rates were 94% and 58% in group L and 75% and 80% in group D, without and with implant removal, respectively. Significantly higher clinical success rates and lower adverse event rates were observed in group D, including higher red blood cell and platelet counts and lower C-reactive protein (CRP) levels. Conclusions Although the effectiveness of LZD and DAP was equivalent in terms of infection control rates for refractory PJIs with gram-positive pathogens, DAP therapy significantly decreased CRP levels and caused fewer adverse events than LZD treatment.

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Novel treatment opportunities in Graves’ orbitopathy

Orvosi Hetilap ◽

10.1556/oh.2014.29963 ◽

2014 ◽

Vol 155 (33) ◽

pp. 1295-1300

Author(s):

Annamária Erdei ◽

Annamária Gazdag ◽

Miklós Bodor ◽

Eszter Berta ◽

Mónika Katkó ◽

...

Keyword(s):

Clinical Experience ◽

Clinical Course ◽

Treatment Protocol ◽

Treatment Modalities ◽

Graves Disease ◽

Novel Treatment ◽

Graves Orbitopathy ◽

Cd20 Antibody ◽

Anti Cd20 ◽

Novel Therapeutic

Graves’ orbitopathy is the most common extrathyroidal manifestation of Graves’ disease. Up to now, curative treatment modalities for the most severe sight-threatening cases have not been developed. Here the authors summarize the treatment protocol of Graves’ orbitopathy and review novel therapeutic options. They review the literature on this topic and present their own clinical experience. The authors point out that anti-CD20 antibody could positively influence the clinical course of Graves’ orbitopathy. Selenium is efficient in mild cases. Further prospective investigations are warranted. Orv. Hetil., 2014, 155(33), 1295–1300.

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Comparison of different techniques for the management of venous steno-occlusive lesions during placement of peripherally inserted central catheter

Scientific Reports ◽

10.1038/s41598-021-89780-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Woo Jin Yang ◽

Danbee Kang ◽

Ji Hoon Shin ◽

Eun Ho Jang ◽

Seung Yeon Noh ◽

...

Keyword(s):

Clinical Success ◽

Alternative Pathway ◽

Transluminal Angioplasty ◽

Second Line ◽

Peripherally Inserted Central Catheter ◽

Central Catheter ◽

Success Rates ◽

Initial Attempt ◽

Technical Success Rate ◽

Occlusive Lesion

AbstractThe purpose of this study is to investigate strategies for peripherally inserted central catheter (PICC) placement in patients with venous steno-occlusive lesion (VSOL). We performed a retrospective cohort study in adults with central or peripheral VSOL who underwent PICC placement procedures from January 2015 to December 2018. Four different strategies [selecting alternative pathway/over the wire (SAP/OTW), percutaneous transluminal angioplasty (PTA), re-puncture in ipsilateral arm (RIA), and catheter placement in the contralateral arm (CICA)] were analyzed and we compared the clinical outcomes by strategy and compared the strategy between central and peripheral VSOLs. During 4 years, 258 PICC procedures performed in patients with VSOLs, 100 PICC were included in the analysis. The overall technical success rate of initial attempt with SAP/OTW was 32.2%. As a second-line technique, PTA was most frequently used in both central (100%) and peripheral (68.2%) VSOL groups. The clinical success rates within 2 months of SAP/OTW, PTA, RIA, CICA were 55.2%, 43.2%, 14.3%, and 33.3%, respectively (P = 0.24). In conclusion, when the SAP/OTW failed, the PTA can be preferred as a second-line technique for both central and peripheral VSOLs. When guidewire passage fails, the operator could adopt the RIA or CICA technique as an alternative method.

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Surgical outcome of percutaneous transhepatic gallbladder drainage in acute cholecystitis: Ten years’ experience at a tertiary care centre

Surgical Endoscopy ◽

10.1007/s00464-021-08573-0 ◽

2021 ◽

Author(s):

Szabolcs Ábrahám ◽

Illés Tóth ◽

Ria Benkő ◽

Mária Matuz ◽

Gabriella Kovács ◽

...

Keyword(s):

Hospital Mortality ◽

Acute Cholecystitis ◽

Conversion Rate ◽

Clinical Success ◽

Definitive Treatment ◽

Success Rates ◽

Female Ratio ◽

Gallbladder Drainage ◽

Percutaneous Transhepatic Gallbladder Drainage ◽

Grade Iii

Abstract Background Percutaneous transhepatic gallbladder drainage (PTGBD) plays an important role in the treatment of elderly patients and/or patients in poor health with acute cholecystitis (AC). The primary aim of this study is to determine how these factors influence the clinical outcome of PTGBD. Moreover, we assessed the timing and results of subsequent cholecystectomies. Patients and Methods We retrospectively examined the results of 162 patients undergoing PTGBD between 2010 and 2020 (male–female ratio: 51.23% vs. 48.77%; mean age: 71.43 ± 13.22 years). Patient’s performance status and intervention outcomes were assessed with clinical success rates (CSR) and in-hospital mortality. The conversion rate (CR) of possible urgent or delayed, elective laparoscopic cholecystectomies (LC) after PTGBD were analysed. Results PTGBD was the definitive treatment in 42.18% of patients, while it was a bridging therapy prior to cholecystectomy (CCY) for the other patients. CSR was 87.97%, it was only 64.29% in grade III AC. In 9.87% of the cases, urgent LC was necessary after PTGBD, and its conversion rate was approximately equal to that of elective LC (18.18 vs. 17.46%, respectively, p = 0.2217). Overall, the post-PTGBD in-hospital mortality was 11.72%, while the same figure was 0% for grade I AC, 7.41% for grade II and 40.91% for grade III. Based on logistic regression analyses, in-hospital mortality (OR 6.07; CI 1.79–20.56), clinical progression (OR 7.62; CI 2.64–22.05) and the need for emergency CCY (OR 14.75; CI 3.07–70.81) were mostly determined by AC severity grade. Conclusion PTGBD is an easy-to-perform intervention with promising clinical success rates in the treatment of acute cholecystitis. After PTGBD, the level of gallbladder inflammation played a decisive role in the course of AC. In a severe, grade III inflammation, we have to consider low CSR and high mortality.

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Therapeutic Application of Monoclonal Antibodies in Pancreatic Cancer: Advances, Challenges and Future Opportunities

Cancers ◽

10.3390/cancers13081781 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1781

Author(s):

Gustavo A. Arias-Pinilla ◽

Helmout Modjtahedi

Keyword(s):

Pancreatic Cancer ◽

Monoclonal Antibodies ◽

Antibody Therapy ◽

Therapeutic Targets ◽

Poor Response ◽

Therapeutic Agents ◽

Therapeutic Interventions ◽

Western World ◽

Wide Range ◽

Novel Therapeutic

Pancreatic cancer remains as one of the most aggressive cancer types. In the absence of reliable biomarkers for its early detection and more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of cancer death in the Western world in the next decade. Therefore, it is essential to discover novel therapeutic targets and to develop more effective and pancreatic cancer-specific therapeutic agents. To date, 45 monoclonal antibodies (mAbs) have been approved for the treatment of patients with a wide range of cancers; however, none has yet been approved for pancreatic cancer. In this comprehensive review, we discuss the FDA approved anticancer mAb-based drugs, the results of preclinical studies and clinical trials with mAbs in pancreatic cancer and the factors contributing to the poor response to antibody therapy (e.g. tumour heterogeneity, desmoplastic stroma). MAb technology is an excellent tool for studying the complex biology of pancreatic cancer, to discover novel therapeutic targets and to develop various forms of antibody-based therapeutic agents and companion diagnostic tests for the selection of patients who are more likely to benefit from such therapy. These should result in the approval and routine use of antibody-based agents for the treatment of pancreatic cancer patients in the future.

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Factors Influencing Clinical Success Following Endovascular Treatment of Type II Endoleaks

Canadian Association of Radiologists Journal ◽

10.1177/0846537120981100 ◽

2020 ◽

pp. 084653712098110

Author(s):

Ramin Hamidizadeh ◽

Emeka Nzekwu ◽

Oliver Halliwell

Keyword(s):

Clinical Success ◽

Strong Predictor ◽

Graft Infection ◽

Mortality Data ◽

Complication Rates ◽

Type Ii ◽

Success Rates ◽

Cyanoacrylate Glue ◽

Embolic Agents ◽

Predictor Of Success

Purpose: To compare long-term outcomes of transarterial (TA) and translumbar (TL) embolization of type II endoleaks (T2E) following EVAR, as well as factors that predict clinical success. Methods: 129 (mean age, 71.4y; range, 53-95) with T2E referred for embolization from August-2003 to December-2017 were retrospectively reviewed. One-hundred-eighty procedures were performed via TA (n = 139) and TL (n = 41) approaches, with 37 patients undergoing 51 reinterventions. Clinical success was defined as absence of endoleak and/or absence of aneurysm sac enlargement on follow-up imaging. Medical comorbidities, procedural data, embolic agents used, presence of successful sac embolization, and 30-day morbidity and mortality data were collected. Results: TL approaches had higher technical success (41/41 vs.122/139, p = .014). Clinical success rates were 52% (N = 58/111) and 62% (N = 23/37) for TA and TL procedures respectively ( p = .34). Looking at all procedures, sac embolization using n-butyl cyanoacrylate glue had higher clinical success compared to other embolic agents ( p = .017-.037). Successful sac access was a strong predictor of success for TA procedures (46/78 vs.12/33, p = .0379). 30-day complication rates were similar between TA (5.8%) and TL (4.9%) approaches. There was 1 death secondary to graft infection following TA embolization. Conclusions: Overall clinical success of TA and TL embolization when considering re-interventions is high. n-butyl cyanoacrylate glue had significantly higher success than other embolic agents ( p = .017-.037). Successful sac access was associated with success for TA procedures.

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One-year outcomes of microhook trabeculotomy versus suture trabeculotomy ab interno

Graefe s Archive for Clinical and Experimental Ophthalmology ◽

10.1007/s00417-021-05333-7 ◽

2021 ◽

Author(s):

Hiroshi Yokoyama ◽

Masashi Takata ◽

Fumi Gomi

Keyword(s):

Survival Analysis ◽

Clinical Success ◽

Treatment Success ◽

Medication Use ◽

Glaucoma Surgery ◽

Success Rates ◽

Kaplan Meier ◽

One Year ◽

Ab Interno

Abstract Purpose To compare clinical success rates and reductions in intraocular pressure (IOP) and IOP-lowering medication use following suture trabeculotomy ab interno (S group) or microhook trabeculotomy (μ group). Methods This retrospective review collected data from S (n = 104, 122 eyes) and μ (n = 42, 47 eyes) groups who underwent treatment between June 1, 2016, and October 31, 2019, and had 12-month follow-up data including IOP, glaucoma medications, complications, and additional IOP-lowering procedures. The Kaplan–Meier survival analysis was used to evaluate treatment success rates defined as normal IOP (> 5 to ≤ 18 mm Hg), ≥ 20% reduction of IOP from baseline at two consecutive visits, and no further glaucoma surgery. Results Schlemm’s canal opening was longer in the S group than in the μ group (P < 0.0001). The Kaplan–Meier survival analysis of all eyes showed cumulative clinical success rates in S and µ groups were 71.1% and 61.7% (P = 0.230). The Kaplan–Meier survival analysis of eyes with preoperative IOP ≥ 21 mmHg showed cumulative clinical success rates in S and μ groups were 80.4% and 60.0% (P = 0.0192). There were no significant differences in postoperative IOP at 1, 3, and 6 months (S group, 14.9 ± 5.6, 14.6 ± 4.5, 14.6 ± 3.9 mmHg; μ group, 15.8 ± 5.9, 15.2 ± 4.4, 14.7 ± 3.7 mmHg; P = 0.364, 0.443, 0.823), but postoperative IOP was significantly lower in the S group at 12 months (S group, 14.1 ± 3.1 mmHg; μ group, 15.6 ± 4.1 mmHg; P = 0.0361). There were no significant differences in postoperative numbers of glaucoma medications at 1, 3, 6, and 12 months (S group, 1.8 ± 1.6, 1.8 ± 1.5, 2.0 ± 1.6, 1.8 ± 1.5; μ group, 2.0 ± 1.6, 2.0 ± 1.6, 2.1 ± 1.6, 2.2 ± 1.7; P = 0.699, 0.420, 0.737, 0.198). Conclusion S and µ group eyes achieved IOP reduction, but μ group eyes had lower clinical success rates among patients with high preoperative IOP at 12 months.

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Bone and Joint Infections among Hematopoietic Stem Cell Transplant Recipients

Journal of Bone and Joint Infection ◽

10.7150/jbji.38120 ◽

2019 ◽

Vol 4 (5) ◽

pp. 209-215

Author(s):

Cybele Lara Abad ◽

Vania Phuoc ◽

Prashant Kapoor ◽

Pritish K. Tosh ◽

Irene G. Sia ◽

...

Keyword(s):

Stem Cell ◽

Septic Arthritis ◽

Hematopoietic Stem Cell ◽

Joint Infection ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Joint Infections ◽

Bone And Joint Infections ◽

Prosthetic Joint ◽

Increased Risk

Abstract. Background: Hematopoietic stem cell transplantation (HSCT) recipients are at increased risk for infection. This study describes bone and joint infections (BJI) among HSCT recipients.Methods: We reviewed 5861 patients who underwent HSCT at Mayo Clinic, Rochester, MN from January 1, 2005 through January 1, 2015 for study inclusion. BJI was defined as native septic arthritis, prosthetic joint infection, osteomyelitis, and orthopedic implant infection. All adults with BJI after HSCT were included in the analysis.Results: Of 5861 patients, 33 (0.6%) developed BJI. Native joint septic arthritis was the most common BJI occurring in 15/33 (45.4%) patients. Patients were predominantly male (24/33, 72.7%), with median age of 58 (range 20-72) years. BJI was diagnosed a median of 39 (range 1-114) months after allogeneic (14/33, 42.4%) or autologous (19/33, 57.6%) HSCT. Organisms were recovered via tissue (24/27, 88.9%), synovial fluid (13/17, 76.5%), and/or blood cultures (16/25, 64%). Most underwent surgical debridement (23/33, 69.7%). Patients were followed a median of 78.3 months (range 74-119). Therapy was unsuccessful in 4/33 (12.1%), with death related to the underlying BJI in two (50%). Failure occurred a median of 3.4 (0.1-48.5) months from diagnosis. At last follow up, 7/33 (21.2%) patients were alive. Median overall survival was 13 months (0.07-70.6).Conclusion: BJI among HSCT recipients is infrequent. The most common infection is native joint septic arthritis. Pathogens appear similar to patients without HSCT. Treatment involving surgical-medical modalities is successful, with most patients surviving >1 year after BJI.

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