Lower Risk Of Adverse Events Research Articles

Thrombosis with thrombocytopenia syndrome associated with COVID-19 vaccines.

BackgroundCurrent vaccines for the Coronavirus Disease of 2019 (COVID-19) have demonstrated efficacy with low risk of adverse events. However, recent reports of thrombosis with thrombocytopenia syndrome (TTS) associated with adenovirus vector vaccines have raised concern.ObjectiveThis narrative review summarizes the current background, evaluation, and management of TTS for emergency clinicians.DiscussionTTS, also known as vaccine-induced immune thrombotic thrombocytopenia, is a reaction associated with exposure to the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and AD26.COV2·S (Johnson & Johnson) vaccine, which may result in thrombocytopenia and thrombotic events. There are several case series of patients diagnosed with TTS, but the overall incidence is rare. TTS is characterized by exposure to one of the aforementioned vaccines 4–30 days prior to presentation, followed by thrombosis, mild-to-severe thrombocytopenia, and a positive platelet factor-4 (PF4)-heparin enzyme-linked immunosorbent assay (ELISA). Thrombosis typically involves atypical locations, including cerebral venous thrombosis and splanchnic vein thrombosis. Evaluation should include complete blood count, peripheral smear, D-dimer, fibrinogen, coagulation panel, renal and liver function, and electrolytes, as well as PF4-heparin ELISA if available. Consultation with hematology is recommended if suspected or confirmed. Treatment may include intravenous immunoglobulin and anticoagulation, while avoiding heparin-based agents and platelet transfusion.ConclusionsWith increasing vaccine distribution, it is essential for emergency clinicians to be aware of the evaluation and management of this condition.

Prognostic Utility of a Modified HEART Score When Different Troponin Cut Points Are Used.

Although the recommended cut point for cardiac troponin (cTn) is the 99th percentile, many institutions use cut points that are multiples higher than the 99th percentile for diagnosing acute myocardial infarction (AMI). Prior studies have shown that patients with a HEART score (HS) ≤ 3 and normal serial cTn values (modified HS) are at low risk for adverse events. This study aimed to evaluate the prognostic utility of the HS when various cTn cut points are used. This was a substudy of High Sensitivity Cardiac Troponin T assay for RAPID Rule-out of Acute Myocardial Infarction (TRAPID-AMI), a multicenter, international trial evaluating a rapid rule-out AMI study using high-sensitivity cardiac troponin T (hs-cTnT). One-thousand two-hundred eighty-two patients were evaluated for AMI from 12 centers in Europe, United States, and Australia from 2011 to 2013. Blood samples of hs-cTnT were collected at presentation and 2 hours, and each patient had a HS calculated. The US Food and Drug Administration approved 99th percentile for hs-cTnT (19 ng/L) was used. There were 213 (17%) AMIs. Within 30 days, there were an additional 2 AMIs and 8 deaths. The adverse event rates at 30 days (death/AMI) for a HS ≤ 3 and nonelevated hs-cTnT over 2 hours using increasing hs-cTnT cut points ranged from 0.6% to 5.1%. Using the recommended 99th percentile cut point for hs-cTnT, the combination of a HS ≤ 3 with nonelevated hs-cTnT values over 2 hours identifies a low-risk cohort who can be considered for discharge from the emergency department without further testing. The prognostic utility of this strategy is greatly lessened as higher hs-cTnT cut points are used.

Continuous bladder irrigation after transurethral resection of non-muscle invasive bladder cancer for prevention of tumour recurrence: a systematic review.

Non-muscle invasive bladder cancer (NMIBC) can recur despite transurethral resection of bladder tumour (TURBT) that clears macroscopic disease, partly from re-implantation of exfoliated cells. Immediate instillation of intravesical chemotherapy (IC) can reduce recurrence, is guideline-recommended but is under-utilized. Continuous bladder irrigation (CBI) immediately post-TURBT is postulated to prevent re-implantation, and may provide a simple, cheap and practical alternative. We undertook a systematic review to assess the effect of CBI on NMIBC recurrence. Following PRISMA guidelines, relevant publications were identified by online search of databases, including Ovid Medline and EMBASE (1980-2019). All published prospective randomized controlled trials comparing CBI post-TURBT to a control group were included. The primary end-point was recurrence. Our search yielded 514 studies, of which six met inclusion criteria. Two studies (935 participants), albeit without peer-reviewed publication, comparing CBI to no CBI both showed a reduction in recurrence at 2 years. Four publications from three trials (331 participants) compared CBI to IC, showing similar recurrence rates at 1year (odds ratio 1.29, 95% confidence interval 0.78-2.13) but a lower risk of adverse events (6-34% versus 27-48%). CBI post-TURBT appears to yield 1-year recurrence rates of NMIBC comparable to immediate IC. However, existing studies are small and of heterogenous design, precluding definitive conclusions. Further trials are required to determine if CBI can be implemented routinely to reduce NMIBC recurrence, as well as the optimal irrigant, volume and duration.

IsAb: a computational protocol for antibody design.

The design of therapeutic antibodies has attracted a large amount of attention over the years. Antibodies are widely used to treat many diseases due to their high efficiency and low risk of adverse events. However, the experimental methods of antibody design are time-consuming and expensive. Although computational antibody design techniques have had significant advances in the past years, there are still some challenges that need to be solved, such as the flexibility of antigen structure, the lack of antibody structural data and the absence of standard antibody design protocol. In the present work, we elaborated on an in silico antibody design protocol for users to easily perform computer-aided antibody design. First, the Rosetta web server will be applied to generate the 3D structure of query antibodies if there is no structural information available. Then, two-step docking will be used to identify the binding pose of an antibody-antigen complex when the binding information is unknown. ClusPro is the first method to be used to conduct the global docking, and SnugDock is applied for the local docking. Sequentially, based on the predicted binding poses, in silico alanine scanning will be used to predict the potential hotspots (or key residues). Finally, computational affinity maturation protocol will be used to modify the structure of antibodies to theoretically increase their affinity and stability, which will be further validated by the bioassays in the future. As a proof of concept, we redesigned antibody D44.1 and compared it with previously reported data in order to validate IsAb protocol. To further illustrate our proposed protocol, we used cemiplimab antibody, a PD-1 checkpoint inhibitor, as an example to showcase a step-by-step tutorial.

Immunohistochemical localization and pharmacokinetics of the anti-MRSA drug teicoplanin in rat kidney using a newly developed specific antibody.

We prepared a polyclonal antibody against a teicoplanin (TEIC)-bovine serum albumin conjugate that was specific to both conjugated and free forms of TEIC. We demonstrated that this antibody could be used to detect the time-dependent localization of TEIC in rat kidneys. Immunohistochemistry revealed immunoreactivity specifically in the microvilli and apical cytoplasm of epithelial cells in proximal tubule segments S1 and S2, 1h after intravenous TEIC injection, with higher staining intensity in the S2 segments. The epithelial cells of S3 segments showed moderate immunostaining with a few cells exhibiting nuclear staining. Furthermore, we found that the distal tubules and collecting ducts contained both TEIC-positive and -negative cells. TEIC immunoreactivity decreased rapidly over time; only weak staining remained in the S3 segments, distal tubules, and collecting ducts 24h after administration. No staining was detected 7days after injection. These results were significantly different from those of our previous study obtained using vancomycin, which showed moderate staining in the proximal tubule segments S1 and S2, distal tubules, and the collecting ducts 8days after administration. The lower TEIC accumulation in tissues may account for a lower risk of adverse events compared to that using vancomycin.

Efficacy of a 3-day pretravel schedule of tafenoquine for malaria chemoprophylaxis: a network meta-analysis.

Chemoprophylaxis with weekly doses of tafenoquine (200mg/day for 3days before departure [loading dose], 200mg/week during travel and 1-week post-travel [maintenance doses]) is effective in preventing malaria. Effectiveness of malaria chemoprophylaxis drugs in travellers is often compromised by poor compliance. Shorter schedules that can be completed before travel, allowing 'drug-free holidays', could increase compliance and thus reduce travel-related malaria. In this meta-analysis, we examined if a loading dose of tafenoquine alone is effective in preventing malaria in short-term travellers. Four databases were searched in November 2020 for randomized controlled trials (RCTs) that assessed efficacy and/or safety of tafenoquine for chemoprophylaxis. Network meta-analysis using the generalized pair-wise modelling framework was utilized to estimate the odds ratio (OR) of malaria infection in long-term (>28days) and short-term (≤28days) travellers, as well as adverse events (AEs) associated with receiving loading dose of tafenoquine alone, loading dose of tafenoquine followed by maintenance doses, loading dose of mefloquine followed by maintenance doses, or placebo. Nine RCTs (1714 participants) were included. In long-term travellers, compared to mefloquine, tafenoquine with maintenance doses (OR = 1.05; 95% confidence interval [CI]: 0.44-2.46) was equally effective in preventing malaria, while there was an increased risk of infection with the loading dose of tafenoquine alone (OR = 2.89; 95% CI: 0.78-10.68) and placebo (OR = 62.91; 95% CI: 8.53-463.88). In short-term travellers, loading dose of tafenoquine alone (OR = 0.98; 95% CI: 0.04-22.42) and tafenoquine with maintenance doses (OR = 1.00; 95% CI: 0.06-16.10) were as effective as mefloquine. The risk of AEs with tafenoquine with maintenance doses (OR = 1.03; 95% CI: 0.67-1.60) was similar to mefloquine, while loading dose of tafenoquine alone (OR = 0.58; 95% CI: 0.20-1.66) was associated with lower risk of AEs, although the difference was not statistically significant. For short-term travellers, loading dose of tafenoquine alone was equally effective, had possibly lower rate of AEs, and likely better compliance than standard tafenoquine or mefloquine chemoprophylaxis schedules with maintenance doses. Studies are needed to confirm if short-term travellers remain free of infection after long-term follow-up. The meta-analysis was registered in PROSPERO (CRD42021223756). Tafenoquine is the latest approved drug for malaria chemoprophylaxis. A loading dose of tafenoquine (200mg/day for 3days before departure) is as effective in preventing malaria in short-term (≤28days) travellers as chemoprophylaxis schedules of tafenoquine or mefloquine with maintenance doses, allowing travellers to have a 'drug-free holiday'.

Safety issues in endoscopy ultrasound-guided interventions using lumen apposing metal stents.

Lumen-apposing metal stents (LAMS) are recently introduced devices that allow to create anastomoses. The indications for LAMS placement are increasing and currently these stents can be used in multiple clinical situations such as endoscopic drainage of pancreatic fluid collections (PFCs), endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS), endoscopic ultrasound gallbladder drainage (EUS-GBD), endoscopic ultrasound gastrojejunostomy (EUS-GJ). Since their introduction, they have revealed to allow a higher rate of technical and clinical success, and potentially lower risk of adverse events (AEs) compared with previously available devices. Despite ongoing innovation, any advanced intervention carries risks of AEs. These AEs may occur during the deployment or can be delayed because of the consequent effects of the procedure and/or stent itself. This review represents an overview of current indications, technical and clinical results, with an extensive focus on safety issues related to placement and on long-term indwelling related ones.

Safety and Efficacy of Thrombin for Bleeding Gastric Varices: A Systematic Review and Meta-Analysis

The optimal therapy for bleeding-related gastric varices is still a controversial topic. There is a paucity of literature that comprehensively summarizes the available literature regarding safety and efficacy of thrombin in bleeding gastric varices. Four independent reviewers performed a comprehensive review of all original articles published from inception to October 2020, describing the use of thrombin for management of bleeding gastric varices. Primary outcomes were (1) pooled early and late rebleeding rate, (2) pooled gastric variceal related mortality rate, (3) pooled rescue therapy rate, and (4) pooled adverse event rate with the use of thrombin in bleeding gastric varices. The meta-analysis was performed and the statistics were two-tailed. Finally, probability of publication bias was assessed using funnel plots and with Egger's test. Eleven studies were included in the analysis after comprehensive search. This yielded a pooled early rebleeding rate of 9.3% (95% CI 4.9-17) and late rebleeding rate 13.8% (95% CI 9-20.4). Pooled rescue therapy rate after injecting thrombin in bleeding gastric varices was 10.1% (95% CI 6.1-16.3). The pooled 6-week gastric variceal-related mortality rate after injecting thrombin in bleeding gastric varices was 7.6% (95% CI 4.5-12.5). There were a total of four adverse events out of a total of 222 patients with pooled adverse event rate after injecting thrombin in bleeding gastric varices was 5.6% (95% CI 2.9-10.6). In summary, the systematic review and meta-analysis on the use of thrombin for bleeding gastric varices suggest low rates of rebleeding and minimal rates of adverse events. While, early and late rebleeding rate and rescue therapy rate are similar to cyanoacrylate-based therapy, the minimal rates of adverse events are perhaps the most important benefit of thrombin. Thus, the current data suggest that thrombin is a very promising therapeutic alternative with low risk of adverse events for bleeding gastric varices.

Refinement of a modified simplified Pulmonary Embolism Severity Index for elderly patients with acute pulmonary embolism

ObjectiveTo evaluate the utility of a modified (i.e., without the variable “Age >80 years”) simplified Pulmonary Embolism Severity Index (sPESI) in elderly patients with acute symptomatic pulmonary embolism (PE), and to derive and validate a refined version of the sPESI for identification of elderly patients at low risk of adverse events. MethodsThe study included normotensive patients aged >80 years with acute PE enrolled in the RIETE registry. We used multivariable logistic regression analysis to create a new risk score to predict 30-day all-cause mortality. We externally validated the new risk score in elderly patients from the COMMAND VTE registry. ResultsMultivariable logistic regression identified four predictors for mortality: high-risk sPESI, immobilization, coexisting deep vein thrombosis (DVT), and plasma creatinine >2 mg/dL. In the RIETE derivation cohort, the new model classified fewer patients as low risk (4.0% [401/10,106]) compared to the modified sPESI (35% [3522/10,106]). Low-risk patients based on the new model had a lower 30-day mortality than those based on the modified sPESI (1.2% [95% CI, 0.4–2.9%] versus 4.7% [95% CI, 4.0–5.4%]). In the COMMAND VTE validation cohort, 1.5% (3/206) of patients were classified as having low risk of death according to the new model, and the overall 30-day mortality of this group was 0% (95% CI, 0–71%), compared to 5.9% (95% CI, 3.1–10.1%) in the high-risk group. ConclusionsFor predicting short-term mortality among elderly patients with acute PE, this study suggests that the new model has a substantially higher sensitivity than the modified sPESI. A minority of these patients might benefit from safe outpatient therapy of their disease.

Safety and Feasibility of Same-session Endoscopic Ultrasound-guided Biopsy and Fiducial Placement in Pancreatic Cancer

ABSTRACT Background In patients with pancreas adenocarcinoma (PDAC), performing endoscopic ultrasound (EUS)-guided fiducial placement at the time of initial EUS-guided biopsies may obviate a second procedure, streamline care, and improve resource utilization. However, the safety of this combined approach is understudied. Methods We retrospectively identified and reviewed cases at a single institution in which patients with PDAC underwent EUS-guided biopsy and same session fiducial placement. Patient and procedural characteristics were abstracted. Intraprocedural and postprocedural adverse events were classified according to the American Society for Gastrointestinal Endoscopy Lexicon for Adverse Events. The percentage of and adverse events occurring within 14 days of the procedure was calculated. Results Thirty-three patients were included in this series (median age 64, 42% male). The median numbers of biopsies performed and fiducials placed were 3 (range 2-7) and 4 (range 1-4), respectively, per patient. A 22-gauge needle was used for the majority of biopsies (81.8%) and all fiducial placements (100%). No definite and one probable adverse event of mild postprocedural pain was noted (3.0%, 1/33). There were no episodes of significant bleeding, pancreatitis or infection. Fiducials were successfully used in the administration of radiation to all patients. Conclusion We report a low risk of adverse events in the setting of combined EUS-guided biopsy and fiducial placement. In the appropriate setting, this approach may streamline care for patients with PDAC while avoiding time, cost, and risks associated with an additional procedure or impacting radiation therapy. Larger, controlled studies are needed to validate the safety and efficacy of this combined approach.

The qualitative method for a humanisation of research.

Huge progress in scientific research, added to vast investments, have allowed to develop vaccines against the virus responsible for Sars-Cov-2 in times unimaginable, until recently (1). The use of these vaccines has documented their high efficacy and very low risk of adverse events. Undergoing vaccination campaigns around the world are changing the history of the COVID-19 pandemic. Never before has scientific research been a topic of widespread interest as in this period. [...].

Efficacy and Tolerability of Thermocoagulation Treatment of High-Grade Cervical Intraepithelial Neoplasia

Purpose: Cervical cancer is still one of the main causes of cancer and mortality in women, especially in low- and middle-income countries, although it is a completely preventable disease through the detection and treatment of pre-cancer lesions. We evaluated the efficacy and tolerability of thermocoagulation treatment of high-grade cervical intraepithelial neoplasia (CIN 2 and 3). Methods: We evaluated 115 women with high-grade cervical intraepithelial neoplasia, 54 with CIN 2 and 61 with CIN 3, confirmed by biopsy and without previous treatment, from January 2016 to December 2018, undergoing thermocoagulation treatment at the Lower Genital Tract Pathology and Colposcopy Service of the Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. Results: The mean age was 33.11 years (SD = 9.83) for CIN 2 and 35.28 years (SD = 7.97) for CIN 3 patients. Treatment efficacy was 90.8% in CIN 2 and 94.9% in CIN 3 cases. Pain was the main symptom reported at the time of treatment, occurring more frequently in the CIN 3 group (49.1% versus 27.8% in the CIN 2 group). As the more important long-term complication, there were 3 cases of pelvic inflammatory disease in CIN 2 (5.6%) and 3 in CIN 3 group (5.0%). The percentage of residual lesion was very low in both groups, 5 in CIN 2 group (9.2%) and 2 in CIN 3 group (3.4%). Conclusion: Thermocoagulation is an effective method for the treatment of cervical pre-cancer lesions (CIN 2 and CIN 3), with a low risk of adverse events and complications.

The role of endoscopic ultrasound in diagnosis and staging of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a malignant neoplasia with an incidence and a prevalence that are progressively growing. It is estimated that in 2030 it will be the third most common tumor, after lungs and liver. This is due at first because of a delay in the development of new therapies able to change PDAC patients' prognosis and also because at diagnosis the tumor is already in advanced stages. During last years, endoscopic ultrasound (EUS), thanks to its versatility, became the first-choice technique in pancreatic diseases. EUS can be used, in example, in the screening of high-risk subjects (HRI) for the development of PDAC. The screening program is reserved to subjects with germinal mutation in high risk genes and subjects with a familial pancreatic cancer history. EUS was found to be a technique highly sensitive with a slightly good specificity in the detection of pancreatic lesions in HRIs; its diagnostic accuracy is superior to MRI and CT-scan, most of all for small size lesions (respectively 93%, 67% and 53%). A fundamental role of EUS is represented by the PDAC diagnosis. Even in this case a higher sensitivity respect to MRI and CT-scan can be observed (94% vs 79% vs 74%). The diagnostic ability could be improved by the use of ancillary techniques as elastography or contrast agents. Furthermore, with EUS it is possible to obtain a cytological or a histological specimen for the diagnosis of PDAC with low risk of adverse events and a high diagnostic accuracy. Considering therapeutic approaches, EUS can be used for pain control performing the celiac plexus neurolysis; new future insights can be found in the possibility of ablative treatments of pancreatic solid neoplasia.

PND9 Comparative Efficacy and Safety of Ozanimod Versus Teriflunomide for Relapsing-Remitting Multiple Sclerosis: A Matching-Adjusted Indirect Comparison

Ozanimod is a selective S1P1,5 modulator approved in the US for relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head data, matching-adjusted indirect comparisons (MAICs) can be used to compare oral disease-modifying therapies (DMTs) in RRMS. The objective of this study was to compare the relative efficacy/safety of ozanimod 1.0 mg and teriflunomide (TEF) 14 mg. A systematic literature review identified clinical trials evaluating efficacy/safety of ozanimod and TEF. Individual patient data (IPD) were obtained from the ozanimod SUNBEAM and RADIANCE Part B trials, and aggregate-level data were obtained from 6 TEF trials. Heterogeneity was observed between ozanimod and TEF trials in Expanded Disability Status Scale scores, gadolinium-enhanced lesions, disease duration from symptom onset, prior relapse and DMT use, age, sex, region, and weight. An unanchored (no common comparator) MAIC was conducted adjusting for imbalances between studies by weighting the IPD for ozanimod to match mean baseline characteristics for TEF. Outcomes of interest were assessed: annualized relapse rate (ARR), proportion of patients relapsed, confirmed disability progression (CDP) sustained for 12 and 24 weeks, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs. After matching, baseline patient characteristics were balanced between ozanimod and TEF. Compared with TEF, ozanimod demonstrated improvements in ARR (rate ratio [RR]: 0.73; 95% CI: 0.62–0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44–0.70), overall AEs (OR: 0.35; 95% CI: 0.29–0.43), SAEs (OR: 0.53; 95% CI: 0.37–0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09–0.21) and similar CDP at 12 (RR: 0.80; 95% CI: 0.61–1.05) and 24 (RR: 0.80; 95% CI: 0.59–1.08) weeks. Ozanimod was associated with improved relapse outcomes and lower risks of AEs over 1–2 years of follow-up compared with TEF, with no differences in CDP.

Efficacy and Safety of Nab-Paclitaxel Plus S-1 versus Nab-Paclitaxel Plus Gemcitabine for First-Line Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma.

ObjectiveNab-paclitaxel plus gemcitabine (nab-P/G) has been established as a standard first-line treatment in metastatic pancreatic ductal adenocarcinoma (PDAC). S-1, as an oral fluoropyrimidine derivative, demonstrated effective for PDAC. This study aimed to evaluate the efficacy and safety of first-line chemotherapy with nab-paclitaxel plus S-1 (nab-P/S) versus nab-P/G in patients with advanced PDAC.MethodsPatients with advanced PDAC receiving nab-P/S (n = 65) or nab-P/G (n = 45) as first-line chemotherapy between November 2013 and June 2019 were reviewed.ResultsThe objective response rate (ORR) and disease control rate were numerically higher with nab-P/S than with nab-P/G (38.5% vs 28.9%, P = 0.30, 73.8% vs 66.7%, P = 0.42, respectively). ORRs of the primary lesion were similar for both groups (30.8% and 22.2%, P = 0.32). The median progression-free survival and overall survival were comparable between the two groups (5.5 vs 5.7 months, P = 0.34, 10.2 vs 11.3 months, P = 0.74, respectively). Nab-P/S was associated with a numerically lower risk of adverse events, especially hematologic adverse events.ConclusionNab-P/S could be a convenient alternative with similar efficacy and a favorable safety profile compared with nab-P/G as first-line chemotherapy for advanced PDAC, as well as an option for neoadjuvant therapy.

Continuous Bladder Irrigation after Transurethral Resection of Non-Muscle Invasive Bladder Cancer for Prevention of Tumour Recurrence – A Systematic Review

Non-muscle invasive bladder cancer (NMIBC) has a high recurrence rate despite transurethral resection of bladder tumour (TURBT) for clearance of macroscopic disease, partly as a result of seeding from exfoliated malignant cells. The immediate instillation of intravesical chemotherapy (IC) can reduce recurrence and is guideline-recommended but has low usage. It is postulated that continuous bladder irrigation (CBI) immediately post TURBT can itself prevent re-implantation and reduce recurrence, which may provide a simple, cheap and practical alternative to IC. We undertook a systematic review of the literature to assess the effect of CBI on NMIBC recurrence. Following PRISMA guidelines, relevant publications were identified from an online search of the literature using databases including Ovid Medline and EMBASE between 1980 to 2018. All published prospective randomized controlled trials (RCTs) which compared CBI post-TURBT to a control group were included. The primary endpoint of the study was recurrence Our search yielded 514 studies of which six met our inclusion criteria. Two studies (935 participants) comparing CBI to no CBI showed a reduction in recurrence at 2 years. Four publications from 3 trials (331 participants) compared CBI to IC, showing comparable recurrence rates at 1 year (OR 1.29, 95% confidence interval 0.78 to 2.13) but a lower risk of adverse events (6-34% vs 27-48%). CBI post TURBT appears to yield one-year recurrence rates of NMIBC comparable to immediate IC. However, existing studies are small and of heterogenous design, precluding definitive conclusions. Further trials are required to determine if CBI can be implemented routinely to reduce NMIBC recurrence, as well as the optimal irrigant, volume and duration.

Evaluation of an autologous cancer vaccine for the treatment of metastatic canine hemangiosarcoma: a preliminary study

BackgroundCanine hemangiosarcoma (HSA) is an aggressive cancer arising from multipotential bone marrow-derived stem cells. Anthracycline chemotherapy drugs have been the mainstay adjuvant chemotherapy following surgery with only modest improvement in survival and an attendant risk for adverse events. Immunotherapy, using a whole cell autologous cancer vaccine adjuvanted with MIM-SIS, may improve outcomes for dogs with HSA with a lower risk for adverse events compared with chemotherapy.ResultsIn cultured DH82 canine monocyte-like cells, autologous cancer vaccines prepared from 13 dogs with HSA increased MHC-II surface expression ranging from 20.0-60.4% on single-stained cells, CD80 surface expression ranging from 23.7–45.9% on single-stained cells, and MHC-II/CD80 surface expression ranging from 7.2–20.1% on double-stained cells. Autologous cancer vaccines were able to, on average, stimulate an up-regulation of MHC-II and CD80 by 48-fold as compared to media only (MHC-II + CD80 + cells: 12.19 ± 3.70% vs. 0.25 ± 0.06%; p < 0.001). The overall median survival time for dogs treated with the autologous cancer vaccine was 142 days (range, 61 to 373 days). Dogs treated with the autologous cancer vaccine or maximum tolerated dose (MTD) chemotherapy had significantly (P < 0.001) longer survival than dogs treated with surgery alone. The 1-year survival rate was 12.5% for dogs treated with the autologous cancer vaccine, and 0% for dogs treated with surgery alone or MTD chemotherapy. No adverse events were observed in the dogs treated with the autologous cancer vaccine.ConclusionsThe adjuvanted autologous cancer vaccine is capable of up-regulating MHC-II and CD80 in cultured canine monocyte-derived cells, which are important stimulatory molecules in generating an immune response and improves survival time in dogs with metastatic (stage III) HSA when compared to surgical treatment alone. Autologous cancer vaccine-treated dogs had survival similar to those dogs treated with MTD chemotherapy without any observed adverse events. This autologous cancer vaccine represents an effective form of individualized immunotherapy that is an appealing option for dog owners not wanting to pursue adjuvant chemotherapy for HSA.

Correlation Between Patients With Methicillin-Resistant Staphylococcus aureus (MRSA) Nares Colonization and MRSA Diabetic Foot Infections.

Infectious Diseases Society of America diabetic foot infection (DFI) guidelines indicate empiric methicillin-resistant Staphylococcus aureus (MRSA) coverage for patients with a history of MRSA infection, when local prevalence of MRSA is high, or infection is clinically severe. These recommendations may lead to overutilization of empiric MRSA coverage, which can result in serious consequences. A strong negative predictive value (NPV) has been reported in literature for pneumonia, and recently, for all anatomical sites of infection. While these findings are promising, further validation is needed before clinicians may confidently use MRSA nares to guide empiric therapy for DFIs. A retrospective electronic medical record review was completed between October 1, 2013 and October 1, 2019. Patients met inclusion criteria if they were at least 18, admitted with a DFI, had MRSA nares test results, and DFI cultures. Patients were excluded if pregnant or MRSA infection within 1 year prior to index admission for DFI. A total of 200 patients met inclusion criteria. The majority of study participants were male with a mean age of 63. NPV of MRSA nares for MRSA DFIs was determined to be 94% and positive predictive value 58%. Sensitivity and specificity were 56% and 94%, respectively. Results of this study are consistent with prior literature supporting strong correlation of NPV for MRSA nares. The DFIs evaluated suggest a strong NPV of MRSA nares for MRSA DFIs, which may allow for faster de-escalation of empiric anti-MRSA antibiotic therapy and lower risk of adverse events associated with anti-MRSA therapy.

Adverse Events of Intense Pulsed Light Combined With Meibomian Gland Expression Versus Meibomian Gland Expression in the Treatment of Meibomian Gland Dysfunction.

To analyze the occurrence and causes of adverse events (AEs) in intense pulsed light (IPL) combined with meibomian gland expression (MGX) and MGX treatment alone for meibomian gland dysfunction (MGD). A retrospective study was conducted on MGD patients treated in Wuhan Aier Hankou Eye Hospital from February 2018 to October 2019 to compare the AEs between IPL-MGX and MGX groups. Relevant AEs that occurred during the treatment and within 1 month after the patients' last treatment were recorded and the causes of the AEs were analyzed. A total of 2,282 patients received IPL-MGX and 1,407 received MGX treatment. No serious AEs occurred in both groups. There were 74 AEs in the IPL-MGX group, with an incidence of 3.24%, including 14 significant AEs (2 cases of epidemic keratoconjunctivitis, 1 recurrent herpes simplex keratitis (HSK), 9 new onsets of floaters, 1 recurrent glaucomatocyclitic crises, and 1 recurrent iridocyclitis). There were 27 AEs in the MGX group with a rate of 1.92%, including 4 significant AEs (2 cases of keratoconjunctivitis epidemic, 2 new cases of floaters). Compared with the IPL-MGX group, the incidence of AEs in the MGX group was lower (P = 0.017). Both IPL-MGX and MGX treatment are safe therapies with low risk for AEs. IPL treatment is not recommended for young children (age 10 or less) as well as patients with anterior uveitis or glaucomatocyclitic crises. The previous history of HSK and eyes with high myopia are advised to exercise caution in IPL treatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Feasibility Trial of an eHealth Intervention for Health-Related Quality of Life: Implications for Managing Patients with Chronic Pain during the COVID-19 Pandemic.

Purpose: This study was conducted to determine the feasibility of providing an eHealth intervention for health-related quality of life (HRQOL) to facilitate patient self-management. Methods: A randomized controlled trial was conducted from 2019–2020 within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation. Eligible patients included those with chronic low back pain and a SPADE (sleep disturbance, pain interference with activities, anxiety, depression, and low energy/fatigue) cluster score ≥ 55 based on the relevant scales from the Patient-Reported Outcomes Measurement Information System instrument with 29 items (PROMIS-29). Patients were randomized to the eHealth treatment group, which received a tailored HRQOL report and interpretation guide, or to a wait-list control group. The primary outcome was change in the SPADE cluster score, including its five component scales, over 3 months. Secondary outcomes were changes in low back pain intensity and back-related disability. Treatment effects were measured using the standardized mean difference (SMD) in change scores between groups. The eHealth intervention was also assessed by a survey of the experimental treatment group 1 month following randomization. Results: A total of 102 patients were randomized, including 52 in the eHealth treatment group and 50 in the wait-list control group, and 100 (98%) completed the trial. A majority of patients agreed that the HRQOL report was easy to understand (86%), provided new information (79%), and took actions to read or learn more about self-management approaches to improve their HRQOL (77%). Although the eHealth intervention met the criteria for a small treatment effect in improving the overall SPADE cluster score (SMD = 0.24; p= 0.23) and anxiety (SMD = 0.24; p = 0.23), and for a small-to-medium treatment effect in improving depression (SMD = 0.37; p = 0.06) and back-related disability (SMD = 0.36; p = 0.07), none of these results achieved statistical significance because of limited sample size. Conclusion: Given the feasibility of rapid online deployment, low cost, and low risk of adverse events, this eHealth intervention for HRQOL may be useful for patients with chronic pain during the COVID-19 pandemic.