bluuebunny/crossref_metadata_2025 huggingface dataset:
2752. Outcomes of Patients with Stenotrophomonas maltophilia infections treated with Cefiderocol in PROVE (Retrospective Cefiderocol Chart Review) Study
Authors: Marcella Stephen , Friedman Bruce , Cai Bin , Verardi Stefano , Gozalo Laurence , Nguyen Sean T
Published: November 2023

Background

Gram-negative (GN) bacterial resistance remains an urgent global health problem. Cefiderocol (CFDC) has activity against Stenotrophomonas maltophilia (SM) isolates. PROVE is an ongoing international, retrospective study of CFDC use in GN infections (GNI). This report gives the first description of patients infected with SM as the primary infection treated with CFDC.

Methods

Eligible patients received ≥ 72 hours of CFDC during routine clinical practice attributed to a primary SM infection. Patient characteristics, hospital course, and treatment patterns are described. Outcomes of clinical cure and 30-day all-cause mortality (ACM) were examined by infection site, pathogen phenotype, patient characteristics, and treatment patterns. Clinical cure is defined as resolution or improvement in infection signs and symptoms without later relapse.

Results

As of March 2023, 54 patients were treated with CFDC for a primary SM infection at 39 sites in the US and Europe. The median age was 59 years; 72.2% were male. Chronic pulmonary disease (27.8%), moderate or severe renal disease (18.5%), and COVID-19 (14.8%) were the most frequent comorbidities. Respiratory infections were most common (n=38, 70.4%). 72.2% of patients were given CFDC in an ICU setting. Mechanical ventilation and vasopressor support were required in 57.4% and 40.7%, respectively.

31 (57.4%) of SM infections were polymicrobial GNI, 21 (67.7%) being Pseudomonas aeruginosa (Table 1). No SM culture was resistant to CFDC when tested (N=15). The median time from positive culture sample to CFDC therapy was 6 days (interquartile range 4–10). Most (68.5%) of patients had the first dose of CFDC 5 days or more after the index culture was taken (Table 1). CFDC was used as monotherapy in 42.6%. Targeted use with or without preceding failure of other GN antibiotics was 88.9%.

Clinical cure and 30-day ACM were 64.8% and 18.5%, respectively. Monomicrobial and polymicrobial infections had similar clinical cure rates (65.2% and 64.5%), but 30-day ACM was greater for monomicrobial infections (30.4% vs. 9.7%) (Table 1).

Conclusion

Patients with SM treated with CFDC in a real-world setting had mostly respiratory infections. Over half of SM infections were polymicrobial but had similar rates of clinical cure as those that were monomicrobial.

Disclosures

Stephen Marcella, MD, MPH, Shionogi, Inc: contracting work for Shionogi, Inc Bruce Friedman, MD, Shionogi: Honoraria Bin Cai, MD, PhD, Shionogi Inc.: Shionogi employee Stefano Verardi, MD, Shionogi B.V.: Employee Laurence Gozalo, PhD, Shionogi, Inc: Analyst Sean T. Nguyen, PharmD, Shionogi: Employee|Shionogi, Inc: Employee
2764. Experience with dalbavancin in a pediatric hospital
Authors: Leon Maria Deza , Murphy Mark
Published: November 2023

Background

Due to its long half-life allowing for once-weekly dosing, dalbavancin has become an appealing option for the treatment of infections that require prolonged antibiotic courses. While studies have shown non-inferiority of dalbavancin compared to conventional antibiotic regimens, there is limited information regarding its use in the pediatric population. We describe the experience with dalbavancin use in a large pediatric hospital.

Methods

Children and young adults who were seen at Cincinnati Children’s Hospital between the period of July 1st, 2019 and December 31st, 2022 and received antibiotic therapy with Dalbavancin were included in this study. We reviewed the patient’s demographic data, laboratory findings including microbiologic data, clinical course, response to treatment and outcomes. Treatment failure was defined as no response or worsening after initial improvement. Clinical response was also evaluated at day 90 after end of therapy.

Results

We identified 26 children and young adults who received dalbavancin between July 1st 2019 and December 31st 2022 (Table 1). Ages ranged between 6 months and 22 years. Most common indication was osteomyelitis. Side effects were rare and included flushing and transient vision loss, which was later diagnosed as ocular migraine. Seven patients (26.9%) had treatment failure at 90 days, including 33.3% and 18.2% of patients with and without comorbidities, respectively. Ages of patients with treatment failure ranged from 6 months to 20 years. Five of them showed initial improvement during the first week after therapy but required an antibiotic switch due to worsening. Time to failure from first dose of dalbavancin ranged from 10 to 35 days. Of all 7 patients who failed therapy, four had no recovered organisms, two had MRSA and one had MSSA. One patient with no initial recovered organism grew Pseudomonas aeruginosa on a repeat culture.

Characteristics of patients who received dalbavancin between July 1st, 2019 and December 31st,2022

Conclusion

While our population was small, a high treatment failure rate was seen when using dalbavancin, particularly in patients with comorbidities. More data is needed to evaluate its performance in the pediatric population and clinicians should be thoughtful about deciding who is a good candidate for dalbavancin therapy.

Disclosures

All Authors: No reported disclosures
2849. Doxycycline for the Treatment of Urinary Tract Infections
Authors: Zheng Tina , Mehta Monica , Stilwell Allison , Demenagas Nicholas
Published: November 2023

Background

The 2010 IDSA uncomplicated cystitis and pyelonephritis guideline does not recommend doxycycline as an oral option for the treatment of urinary tract infections (UTI). Doxycycline is reported to have 35-60% urinary excretion. Small prospective cohort studies from the 1960-1980s suggest favorable clinical and microbiological outcomes. This multicenter, retrospective study aimed to describe the effectiveness and safety of doxycycline to treat UTIs.

Methods

Patients aged ≥ 18 years who received at least one dose of doxycycline for the treatment of UTI from September 1, 2020 to August 31, 2022 were included. Patients with a positive chlamydia/gonorrhea result, suspected concomitant sexually transmitted infections, asymptomatic bacteriuria, or with urine culture isolates resistant to tetracyclines were excluded. Treatment success was defined as resolution of urinary symptoms on day 3 and the last day of treatment for patients who received their entire doxycycline course while inpatient. Secondary outcomes included clinical recurrence, microbiological success and recurrence, and adverse drug events. Patients who had a partial inpatient doxycycline course met treatment success criteria if they did not re-present for medical care with UTI symptoms within 7 days post-treatment completion.

Results

Seventeen patients were evaluated. Patients were older with a median age of 65 years, and 47% reported antibiotic allergies. Most patients had cystitis (65%), though four patients had pyelonephritis (24%). The most common organism isolated was Klebsiella pneumoniae (24%). Resistance to third-generation cephalosporins, carbapenems, and levofloxacin was 79%, 14%, and 53%, respectively. The median duration of doxycycline treatment was 8 days. Treatment success for the complete inpatient treatment group and the partial inpatient treatment group was 75% (6/8) and 89% (8/9), respectively. Only one patient (6%) experienced syncope attributed to doxycycline.

Conclusion

Despite the limited urinary penetration of doxycycline, this study suggests that it may be an alternative option for treatment of UTIs, particularly in patients with a lack of oral options due to allergies or resistant organisms.

Disclosures

All Authors: No reported disclosures
370. The comparison of adverse events in combination with double beta-lactam antimicrobials: Ampicillin plus Ceftriaxone and Ampicillin/Cloxacillin with bloodstream infections
Authors: Ishikawa Kazuhiro , Kobayashi Daiki , Mori Nobuyoshi
Published: November 2023

Background

Double beta-lactams are used to treat infective endocarditis, but the incidence rate of adverse events is unclear. We aimed to compare the incidence rates of adverse events of ampicillin(ABPC) versus ABPC plus ceftriaxone(CTRX) and ABPC/MPIPC(cloxacillin).

Methods

We retrospectively included adult bacteremia patients admitted to St. Luke's International Hospital and received ABPC, ABPC plus CTRX, and ABPC/MPIPC between 2004 and 2022. We excluded patients on hemodialysis, those with missing data, those who used more than three beta-lactam antimicrobials, and beta-lactam other than ABPC, CTRX, or ABPC/MPIPC. All statistical analysis was done using IBM SPSS.

Results

We included 280, 59, and 43 patients for ABPC, ABPC plus CTRX, and ABPC/MPIPC, respectively. There were significant differences in median age(70.8 [standard deviation: SD 16.6], 64.3[16.7], 56.6[17.5]), male sex(62.1%, 47.5%, 72.1%), qSOFA ≥2 (23.1%, 64.4%, 41.9%), admission in an intensive care unit(6.4%, 40.7%, 14.0%), mechanical ventilation (5.4%, 23.7%, 20.9%), use of vasopressor (10.4%, 32.2%, 23.3%), administration of vancomycin (7.5%, 27.1%, 41.9%) or clindamycin (19.6%, 23.7%, 44.2%) for more than three days, hepatic dysfunction (AST: 42.6[81.5], 120.4[493.0], 54.1[68.5], ALT: 33.1[35.9], 98.2[380.0], 46.6[67.6], anemia(Hgb: 10.8[2.1], 11.6[2.4], 11.9[2.8] and thrombocytopenia (PLT: 203.5[105.0], 154.8[115.0], 255.9[159.7]) on admission. There were significant differences in AKI (9.0%, 12.3%, 30.2%), treatment duration (13.9 [12.1] days, 9.1 [8.7] days 29.0 (19.2) days, and duration of hospitalization 34.1[31.1] days, 48.3 [50.4] days, 51.6 [32.5] days, but no difference in 30 days mortality (4.3%, 6.8%, 2.3%) and 90 days mortality (8.2%, 13.6%, 7.0%). Kaplan-Meier analysis showed no significant difference between ABPC and CTRX plus ABPC in AKI, but there was a significant difference between ABPC and ABPC/MPIPC(figure 1, 2). The hazard ratio of ABPC/MPIPC for AKI was 1.572(95% confidence interval, 1.067-2.315)(figure 3).Figure 1Percent of non-AKI between ABPC and ABPC plus CTRXAbbreviation: AKI, acute kidney injury; ABPC, ampicillin; CTRX, ceftriaxoneFigure 2Percent of non-AKI between ABPC and ABPC/MPIPCAbbreviation: AKI, acute kidney injury; ABPC, ampicillin; MPIPC, cloxacillin

Conclusion

Double beta-lactam therapy with ABPC plus CTRX may be relatively safe, but careful follow-up is needed for platelet count and hepatic function. On the other hand, ABPC/MPIPC has a significantly higher incidence of AKI compared to other antimicrobials.

Factors associated with AKI

Abbreviation: AKI, acute kidney injury; ABPC, ampicillin; MPIPC, cloxacillin; CI, coincidence interval

Disclosures

All Authors: No reported disclosures
579. Clinical and Drug Resistance Characteristics of Providencia spp. Infections
Authors: Kale-Pradhan Pramodini , Lim Lauren , Graskewicz Heather , Malviya Meenal , COYLE M E R E D I T H M , Giuliano Christopher , Johnson Leonard B
Published: November 2023

Background

Providencia is a gram-negative bacillus that colonizes the urinary tract and is often resistant to many antimicrobials. This study aimed to evaluate resistance patterns of Providencia spp (P. spp) and clinical outcomes due to the paucity of topical data.

Methods

A multi-center, descriptive, retrospective chart review of adult patients with P. spp. infections was conducted from January 1, 2020 to May 31, 2022. The primary outcome was to describe the drug resistance patterns of P. spp. isolates. The study’s secondary outcome was to evaluate the clinical outcomes of patients with P. spp infections.

Results

Of 312 patients screened, 243 were excluded primarily for polymicrobial infections. The mean age was 70 years and 39 (56.5%) were males. Of the 69 included cases, 46 (66.7%) were P. stuartii, 21 (30.4%) P. rettgerri, and 2 (2.9%) P. alcalifaciens. The most common infections were bacteremia 38 (55.1%), with urinary and wound being the most frequent bacteremia source; followed by 28 (40.6%) urinary tract and 3 (4.3%) wound infections. 45 patients (65.2%) had urinary catheters. Primary antibiotics used for treatment consisted of ceftriaxone, 25 (36.2%), cefepime, 20 (29%), and meropenem, 10 (14.5%). Five of 69 (7.2%) cases were multidrug resistant and required meropenem. Nineteen patients (27.1%) died during their admission but none related to Providencia infections. Ten of the 69 patients (14.5%) were readmitted within 30 days for reasons unrelated to progression or recurrence of Providencia infections.

Conclusion

Providencia bacteremia was the most common infection. Third generation cephalosporins remain an appropriate choice of antibiotics for P. spp. However, P. stuartii was the only species with multidrug resistance. Future studies should be carried out to confirm this observation.

Disclosures

All Authors: No reported disclosures
642. The impact of novel E1:M407I mutation on replicative fitness of the Chikungunya virus ECSA-IOL strain during infection of mammalian and mosquito cells,
Authors: Khan Bilal A , Ullah Saif , Khan Saeed
Published: November 2023

Background

Chikungunya virus (CHIKV) is an Alpha virus which is transmitted by Aedes genus of mosquitoes. It causes febrile illness with severe arthralgia, myalgia and rashes. Since 2000, the re-emergence of this pathogen have made it a global health security threat as it has caused severe form of diseases with epidemics of large magnitude and also spread to European and American continent. Studies have identified different point mutations in E1 and E2 region associated with virulence and infectivity, which is behind these severe epidemics. Pakistan reported first CHIKV outbreak with more than 30,000 infections from its largest city in 2016 which is already endemic for Dengue virus (DENV).

Methods

32 CHIKV PCR-positive serum samples were collected from molecular pathology section of DUHS followed by RNA extraction and amplifcation of E1 region by PCR. The amplified products were prurified and sanger sequenced by BigDye termination method. Mutation analyses & Bayesian phylogeny was done by bioinformatic tools. CHIKV E1:M407I mutation was cloned in to CHIKV wild type infectious cDNA clone plasmid (SL-CK-1) by site directed mutagenesis (SDS). In vitro viral RNA was synthesized after plasmid linearization, which was electroporated into VERO-CCL-81 cells. M407I mutant virus was recovered from the culture, titrated by plaque assay and sanger sequenced to confirmed the M407I mutation. Viral competition assay was performed in mammalian and mosquitoes cell lines to determine the relative replicative fitness of mutant CHIKV virus over wild type.

Results

Sequence analysis revealed 7 unique mutations in E1 including one mutation (M407I) in more than half of the sequenced samples. Phylogenetic analyses revealed this outbreak was caused by CHIKV-IOL genotype with possible inception from India. Virus competition assay showed relative replicative fitness for CHIKV E1:M407I mutant in Vero-CLL-81 and AAG2 cells have greater advantage while in C6/36, it has slight advantage over wild type virus.

Conclusion

This study reports a novel mutations in E1 protein of CHIKV with fitness advantage over wild type strain. Phylogeny revealed the outbreak was caused by A226-IOL strain with possible origin from ancestral strain of Indian outbreak.

Disclosures

All Authors: No reported disclosures
919. Household Flu Transmission and Healthcare Resource Use among Patients Treated with Baloxavir versus Oseltamivir for Influenza: An Outpatient Prospective Survey in the United States
Authors: Best Jennie H , Sadeghi Mitra H , Sun Xiaowu , Seetasith Arpamas H , Albensi Lisa , Joshi Seema , Zervos Marcus
Published: November 2023

Background

Influenza is a common seasonal infectious disease that has broad medical, economic, and social consequences. Understanding how flu antiviral use affects transmission to household (HH) members is critical to inform clinical practice. Objectives of this study were to compare the incidence of HH transmission (primary) and healthcare resource utilization (HRU, secondary) in influenza patients treated with baloxavir (BALOX) compared with oseltamivir (OSELT). This is the first analysis to examine the effectiveness of BALOX vs OSELT for reducing transmission in a real-world setting in the US.

Methods

Patients were recruited from October 2022 to March 2023 via CVS Pharmacy in the US. Patients were eligible for inclusion if: ≥ 18 years, filled an Rx for BALOX or OSELT ("index" day) ≤ 2 days from flu symptom onset and also reported taking the therapy, had no HH flu ≤ 7 days pre-index, had no COVID ≤ 30 days pre-index, and had ≥ 2 persons in HH. Patients were contacted via email or call center from Days 4 though 8 post-index to inform and/or remind patients about the online survey. Patients completed the survey on Days 6, 7, or 8 post-index. BALOX-treated patients were matched (non-randomized) with up to 3 OSELT-treated patients on same RX fill date. Household transmission (reported by index patient) and all-cause HRU (of the index patient) in the 8 days post-index were assessed using chi-square and Fisher's exact tests.

Results

Of 77,314 unique patients contacted, 1,301 (1.7%) patients consented. Of 356 eligible patients, 275 (89 BALOX-treated and 186 OSELT-treated patients) completed the survey and were included in the analysis. Patients were mean age 45, female (65%), and White (87%). Lower HH transmission was observed with BALOX compared with OSELT therapy (18.0% vs 27.4%; standardized mean difference = 0.23; RR = 0.66; p= 0.09; Figure 1). HRU was also numerically lower in the BALOX-treated group, particularly emergency department visits (0.0% vs 4.3%; p = 0.06; Table 1); no hospitalizations were reported.

Proportion of patients with healthcare resource utilization

Conclusion

The findings in this real-world study suggest that treatment of influenza with BALOX may decrease transmission to household members and reduce healthcare resource utilization compared with OSELT treatment. Future research could validate these findings in larger populations.

Disclosures

Jennie H. Best, PhD, Genentech: Stocks/Bonds Mitra H. Sadeghi, PharmD, Genentech, Inc.: Stocks/Bonds Xiaowu Sun, PhD, CVS: Stocks/Bonds Arpamas H. Seetasith, PhD, Genentech, Inc.: Stocks/Bonds Marcus Zervos, MD, Contrafect: Advisor/Consultant|GSK: Grant/Research Support|Johnson and Johnson: Grant/Research Support|Pfizer: Grant/Research Support
1144. Dissociative Neurological Symptom Reactions Following COVID-19 Vaccination in Adolescents in Japan
Authors: Horikoshi Yuho , Yamanaka Takayuki , Aizawa Yuta , Nakamura Yukitsugu , Shoji Takayo , Okumura Toshihiko , Cho Yoshiaki
Published: November 2023

Background

In 2019, the WHO categorized immunization stress-related reactions as an adverse event following immunization (AEFI). Understanding AEFI is essential for determining an appropriate communication strategy to sustain trust in vaccination. Delayed response to immunization includes dissociative neurological symptom reactions (DNSRs), which are characterized by functional neurological symptoms. DNSRs following immunizations are quite rare, but it is often wrongly linked to causal relationship with vaccines that the public might perceive unnecessary fear. As DNSRs following vaccination in adolescents are currently understudied, the present report aimed to describe the clinical features of DNSRs following COVID-19 vaccination.

Methods

The multicentric study was conducted between July 2021 and March 2023 at seven tertiary pediatric medical centers accepting patients with persistent AEFI. Patients aged 18 years or younger were included. Their charts were reviewed retrospectively for demographic data, symptoms, and the outcomes of DNSRs following COVID-19 vaccination.

Results

In total, 46 patients aged 6 to 17 years were referred for persistent AEFI following COVID-19 vaccination. Among these, eight received the diagnosis of DNSR. Female patients comprised 87% of the cohort. All the patients had received the Comirnaty vaccine (Pfizer). Before DNSR onset, seven and one patient had received their first and second dose of Comirnaty, respectively. Two and one of the eight patients had a mental handicap and autism spectrum disorder, respectively. The DNSR symptoms included weakness (37%), gait irregularity (25%), speech difficulty (25%), paralysis (12%), and non-epileptic seizure (12%). The duration from vaccination to symptom onset ranged from 0 to 14 days (median: 1 day; IQR: 1-2 days). Symptom duration was 0.5-11 months (median: 5 months; IQR: 1-7 months). The outcomes included resolution (25%), improvement (62%) and no change (12%).

Patients with DNSR symptoms

This is summary of patients presenting with DNSRs.

Conclusion

DNSRs following COVID-19 vaccination were observed predominately in female, adolescent patients and had a favorable, long-term outcome.

Disclosures

Yuho Horikoshi, MD, Shionogi Pharm: Grant/Research Support
1149. Contribution of S.pneumoniae Serotypes in Adults with Invasive Pneumococcal Disease (IPD) and Pneumococcal Community-acquired Pneumonia (pCAP)
Authors: Apodaca Kevin , Grant Lindsay , Yan Qi , Theilacker Christian , Ali Mohammad , Pride Michael W , Gessner Bradford D , Jodar Luis
Published: November 2023

Background

Invasive pneumococcal disease (IPD) serotype distribution has been used to infer the serotype distribution of pneumococcal community acquired pneumonia (pCAP) in countries where only IPD data exist. However, serotype distribution of IPD and pCAP may differ. We sought to identify differences in contribution of serotypes causing pCAP versus IPD.

Methods

Eligible countries had serotype data available from adults for both IPD (determined by standard serotyping methods of cultured isolates) and pCAP (determined by serotype-specific urinary antigen detection (UAD) assays or culture for at least three years following PCV13 introduction into the pediatric national immunization program (NIP). Analyses were restricted to serotypes included in UAD assays. We further restricted analysis to serotypes not in PCV13 but detected by UAD assays (serotypes 2, 8, 9N, 10A, 11A, 12F, 15B/C, 17F, 20, 22F, and 33F), because PCV13 introduction into the NIPs has led to vaccine serotype disease reduction. The total positive of these serotypes was the denominator in the serotype-specific proportion calculations for both IPD and pCAP

Results

We included seven countries. IPD serotype as well as pCAP distribution varied substantially across countries, while within countries, IPD and pCAP serotype distribution varied modestly (Figure1, Table 1) For the three most common pCAP serotypes across the seven countries, the absolute differences in the percent due to pCAP across countries were 19% (serotype 8), 10% (serotype 22F) and 10% (serotype 11A). For the same three serotypes, respectively, the absolute differences in the percent due to IPD across countries were 47%, 18%, and 17%. For these same three serotypes, the absolute differences in the percent due to pCAP vs, IPD within a country ranged from 1% to 14%, 1% to 6%, and 2% to 11%.  

Conclusion

pCAP and IPD serotype distribution were relatively aligned within countries. By contrast IPD and pCAP serotype distribution varied substantially across countries. Consequently, while the most accurate data for country-specific pneumococcal vaccine decision-making will come from combined IPD and CAP studies, countries without CAP data should rely on local IPD serotype distribution rather than CAP data from other countries.

Disclosures

Kevin Apodaca, MPH, Pfizer Inc.: Stocks/Bonds Lindsay Grant, PhD, MPH, Pfizer Inc.: Stocks/Bonds Qi Yan, PhD, MS, Pfizer Inc: Stocks/Bonds Christian Theilacker, MD, DTM&H, Pfizer Inc: Stocks/Bonds Mohammad Ali, PhD, Pfizer Inc: Stocks/Bonds Michael W. Pride, PhD, Pfizer: Stocks/Bonds Bradford D. Gessner, M.D., M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Luis Jodar, PhD, Pfizer Inc: Stocks/Bonds
Possible Worlds as Propositions
Authors: Deasy Daniel
Published: November 2023

Realists about possible worlds typically identify possible worlds with abstract objects, such as propositions or properties. However, they face a significant objection due to Lewis (1986), to the effect that there is no way to explain how possible worlds-as-abstract objects represent possibilities. In this paper, I describe a response to this objection on behalf of realists. The response is to identify possible worlds with propositions, but to deny that propositions are abstract objects, or indeed objects at all. Instead, I argue that realists should follow Prior (1971) and others in treating higher-order quantification (e.g. quantification into predicate or sentence position) as a genuine form of quantification in its own right, and so in particular, not to be analysed in terms of first-order quantification over abstract objects. I argue that from this ‘higher-orderist’ perspective, there is a relatively straightforward answer to the question of how possible worlds-as-propositions succeed in representing possibilities.
Real-world efficacy of belimumab in systemic lupus erythematosus: a prospective cohort from a single centre in China
Authors: Zhao Yin , Qi Fumin , Bai Jinyu , Zhang Na , Yang Tong , Sun Wenwen , Li Xin , Wei Wei
Published: November 2023

Objective

The objective of this study was to explore the efficacy and safety of belimumab among Chinese patients with SLE in a real-world setting.

Methods

A prospective cohort study was performed, and SLE patients taking belimumab on a background of standard-of-care (SoC) treatment were consecutively enrolled from July 2021 to December 2022. Based on baseline characteristics, the patients were divided into three groups: the newly diagnosed group, the relapsed group and the refractory group. Patients in the newly diagnosed group were newly diagnosed with SLE within 4 weeks of starting belimumab. Patients in the relapse group had experienced a severe flare. Refractory patients were patients with unsatisfactory GC taper and/or disease activity control. Clinical data were collected, and disease assessments were conducted regularly. Newly diagnosed patients with SoC alone and healthy controls (HCs) were also enrolled.

Results

A total of 123 SLE patients were included in the analysis, with a median follow-up period of 12 months (range 3–18 months). Thirty-three out of 123 patients were newly diagnosed, 32 had relapsed disease, and 58 had refractory disease. The SLE Responder Index 4 (SRI-4) response was achieved with good tolerance by 55.77% of patients at 3 months, 56.63% at 6 months, 63.24% at 9 months, 63.64% at 12 months and 57.14% at 18 months. Serological parameters (anti-dsDNA and C3/C4), SLEDAI-2K and daily prednisone intake were improved overall and in each group. Of the three groups, the newly diagnosed group had the highest SRI-4 rate as well as the greatest improvement in serological parameters and SLEDAI-2K. Compared with newly diagnosed patients with SoC alone, the cumulative prednisone intake of newly diagnosed patients taking belimumab was significantly decreased.

Conclusion

Our data supported the efficacy of belimumab in Chinese SLE patients in a real-life setting. Our study also provided new evidence indicating remarkable achievement of the SRI-4 response during belimumab therapy in newly diagnosed SLE patients.
Closing-wedge Osteotomies: Can We Do and Teach Better?
Authors: Weltsch Daniel , Juels Michaela , Chen Kevin Yining , Talathi Nakul , Silva Mauricio , Thompson Rachel M.
Published: November 2023

Background:

Wedge osteotomies are ubiquitous in pediatric orthopaedics and limb deformity surgery; however, there is no universally preferred methodology for these procedures. This study aims to determine the relative accuracy and effectiveness of several measuring and marking methods to guide best practices for wedge-shaped osteotomies in long bones.

Methods:

An observational cohort study was completed. Orthopaedic residents (postgraduate years 1 to 5) completed 30-degree wedge osteotomies on a sawbone (Pacific Research Lab) femur utilizing a standard oscillating saw under 3 measuring conditions: (1) no measurement tool, (2) 30-degree triangle, and (3) goniometer, in combination with 2 different marking methods: (1) marking pen or (2) pin placement. Demographic characteristics and osteotomy performance (quality, completion time, and accuracy) were assessed. Quality was ranked as perfect (1), mild step-off (2), or gross surface irregularity (3). Multivariate regressions and analysis of variance were performed comparing demographics, osteotomy performance, and measuring methods.

Results:

Twenty-four residents were included for analysis; 6 were female (25%). Female sex was independently associated with longer completion time when evaluating all combined scenarios (138 vs. 99 s, P=0.003) without differences in surface quality or angle accuracy. There were no significant associations between measuring technique and accuracy or surface quality, but use of the goniometer and the triangle both were associated with significantly longer completion time compared with no visual aid (P=0.002 and 0.007). When controlling for measuring technique, use of the pen as a marking technique had significantly shorter completion times (P<0.001), higher surface quality (P<0.001), and better accuracy (P<0.001) than guide pins.

Conclusions:

We recommend the use of a marking pen in combination with the surgeon’s preferred measuring guide to optimize trainees’ performance of closing wedge osteotomies. Future research is necessary to corroborate these findings in a higher fidelity setting, such as a cadaveric study. Further, while male residents complete wedge osteotomies quicker than female residents, quality and accuracy are comparable among trainees. Slower pace should not be conflated with poor performance but rather should inform effective intraoperative teaching for diverse trainees.
Comparison of Two Surgical Approaches for Trimalleolar Ankle Fracture Fixation
Authors: O’ Reilly Kasie , Ní Fhóghlú Cliodhna , Mahon John , Hennessy Orla , Bayer Thomas
Published: November 2023

Ankle fractures account for 10% of all presenting fractures, with research quoting the involvement of the posterior malleolus in around 7% of cases. Trimalleolar fractures are estimated to have greater long-term complications due to the significant disruption to the articular surface of the joint and the reduced weight-bearing potential associated with this. Despite the well-documented role of the posterior malleolus in ankle fractures, its fixation is often a matter of debate. One barrier to this is the potential need for an additional surgical incision. Our study compared two surgical approaches to trimalleolar ankle fracture fixation: One through an extended posterolateral and medial approach (2-incision approach) and one through a combined posterolateral, direct lateral, and medial approach (3-incision approach). Thirty-eight open reduction and internal fixation of trimalleolar ankle fractures were performed by the senior author in a single institution between January 2017 and January 2020. Fifteen underwent a 2-incision approach and 3 separate incisions were used in 23 cases. Outcomes of the two different surgical methods included a postoperative functional score (Ankle-Hindfoot American Orthopedic Foot and Ankle Society), postoperative complications, and evaluation of postoperative radiographs. Twenty-three patients were recruited to the 3-incision group and 15 to the 2-incision group. The utilization of 3 separate incisions for the fixation of trimalleolar fractures showed fewer complications than a 2-incision approach. Further, smoking was positively correlated with reported complications. All other perioperative variables did not reach statistical significance. In our study, a 3-incision approach showed a tendency for lower complication rates in the surgical treatment of trimalleolar ankle fractures compared with a 2-incision approach. In our opinion, a direct approach to the 3 malleoli through individual incisions allows better visualization of the fracture site, including intercalary and incisura fragments, enabling better reduction and avoiding unnecessary destructive tissue handling.

Level of Evidence: Diagnostic Level 2. See Instructions for Authors for a complete description of levels of evidence.
Efficacy and safety of clarithromycin for patients with sepsis or septic shock: a systematic review and meta-analysis
Authors: Zhao Pengyue , Yao Renqi , Yang Jiaqi , Wen Wei , Yao Yongming , Du Xiaohui
Published: November 2023

Background

Clarithromycin exerts an immunomodulatory role in several human diseases. However, whether this effect improves the prognosis in patients with sepsis remains controversial, and higher levels of clinical evidence are urgently needed. To the best of our knowledge, no meta-analysis to date has reported the clinical efficacy and safety of clarithromycin in sepsis.

Methods

A comprehensive literature search of PubMed, EMBASE, and the Cochrane Library was conducted up to December 31, 2022. Only randomized controlled trials comparing the clinical efficacy and safety of clarithromycin with controls among patients with sepsis or septic shock were included. Data were pooled by applying a fixed-effects model and a relative risk (RR) estimate with 95% confidence intervals (CIs) using Review Manager (version 5.3; Cochrane Collaboration, Copenhagen, Denmark).

Results

Three randomized controlled trials involving a total of 910 patients were included. The pooled results confirmed that clarithromycin had no beneficial effect on progression to multiple organ dysfunction syndrome (RR: 1.51; 95% CI: 1.02–2.25; P = 0.04; I
2 = 0%), 28-day mortality (RR: 1.09; 95% CI: 0.87–1.36; P = 0.46; I
2 = 0%), and 90-day mortality (RR: 0.86; 95% CI: 0.71–1.03; P = 0.10; I
2 = 81%) in patients with sepsis or septic shock. Moreover, there was no difference in other serious adverse events between patients who received clarithromycin and those in the control group (RR: 1.02; 95% CI: 0.87–1.19; P = 0.83; I
2 = 18%).

Conclusion

Our meta-analysis did not reveal an improvement to short-term outcomes in patients with sepsis treated with clarithromycin. However, administration of clarithromycin did not increase the risk of adverse events.
A Novel Framework for Optimizing Efficiency and Education in Microsurgical Breast Reconstruction
Authors: Lester Mary E. , Berns Jessica , Dawson Steven , Newsom Keeley , Hartman Brett , Hassanein Aladdin H.
Published: November 2023

Deep inferior epigastric perforator (DIEP) flaps are becoming the most frequent choice for autologous breast reconstruction. There are many benefits to DIEP flaps, but the procedures can be lengthy and have a steep learning curve. The balance of efficiency and education can be difficult to achieve. A framework was implemented to focus on both efficiency and education at each stage of the DIEP flap procedure. The author’s methods to improve efficiency include a two-team approach with assigned roles for faculty and residents. The roles are consistent across the institution. Methods to enhance education include practice in a laboratory-based microsurgical training course and assigning goals for the rotation. Trainees include independent and integrated plastic surgery residents without microsurgical fellows. Bilateral DIEPs are performed with two attendings, and unilateral DIEPs, with one attending. A retrospective review identified patients undergoing DIEP flap reconstruction from 2017 to 2020. Outcome measures include operative time and complications, which are comparable to previously published data. Focusing on education allows residents to learn each stage of the case. The authors present a framework for training residents in DIEP flap reconstruction to optimize efficiency and education.
Use of Rare Anatomical Variant of the Free Fibula Flap to Reconstruct the Nasal Septum
Authors: Yeap Isobel , Ch’ng Sydney
Published: November 2023

The osteocutaneous fibula free flap (FFF)’s skin paddle is commonly vascularized by the septocutaneous (SC) perforators of the peroneal artery that course through the posterior intercrural septum. However, a rare anatomical variant exists in which the skin paddle is vascularized via a separate arterial system to the fibula. We report the case of a 31-year-old man who was planned for osteocutaneous FFF reconstruction of his anterior maxilla and hard palate following resection of nasal septal chondrosarcoma. Intraoperatively, he was found to have a rare anatomical variant: the perforator to the skin paddle arose proximal to the peroneal artery, off the tibioperoneal trunk. This was a fortuitous, rare anatomical variant, as it enabled a double free flap reconstruction from a single donor site—an intraoral fasciocutaneous free flap oriented with its long axis perpendicular to that of an osseous FFF. This particular defect enabled reconstructive freedom beyond that of the standard osteocutaneous free flap, in which the skin paddle orientation is limited by the risk of kinking the septal perforator. This case report summarizes the flap raising technique and the learning points relevant to the osteocutaneous FFF with no SC perforators. The extant literature on this anatomical variant is then summarized. The average estimated rate of FFF with no SC perforators is between 3% and 25%, based on four published studies.
A cost-analysis of managing secondary and apparent treatment-resistant hypertension in a specialist multidisciplinary hypertension clinic
Authors: Rabbitt Louise , Curneen James , Hobbins Anna , Browne Darragh , Joyce Mary , Lappin David , McEvoy John William , Gillespie Paddy , Dennedy Michael Conall
Published: November 2023

Objectives:

A knowledge gap exists around the costs and budget impact of specialist hypertension clinics. This study reports on the cost of providing care in a multidisciplinary hypertension clinic staffed by nephrologist, endocrinologist and cardiologist, which manages patients with suspected secondary hypertension and/or apparent treatment-resistant hypertension. The aim of this study is to provide the evidence required to inform policy and planning care pathways for this patient group.

Methods:

A cost analysis from a healthcare provider perspective using micro-costing techniques was conducted to estimate the direct implementation costs of existing standard practice for the care pathway of patients attending the multidisciplinary hypertension clinic. Sixty-five patients originally recruited for a study of medication adherence in hypertension were included in the sample.

Results:

The total care-pathway cost per patient, taking into account clinic visits, clinical reviews, investigations and MDT discussion, was estimated to be €3277, on average. For the patient subgroups, the average cost was €5644 for patients diagnosed with primary aldosteronism and €1446 for patients diagnosed with essential hypertension.

Conclusion:

There is significant cost associated with providing specialized hypertension care for patients with apparent treatment-resistant hypertension. Given the high rates of nonadherence in this population, it is likely that some of this cost could be avoided with better detection and management of medication adherence in this challenging population. Future studies should consider the cost-effectiveness of this or similar models of care by exploring the benefit to patients and the wider healthcare context of providing care of this type.
Long-term blood pressure variability and frailty risk in older adults
Authors: Fravel Michelle A. , Ernst Michael E. , Woods Robyn L. , Beilin Lawrence , Zhou Zhen , Orchard Suzanne G. , Chowdhury Enayet , Reid Christopher M. , Saifuddin Ekram ARM , Espinoza Sara E. , Nelson Mark R. , Stocks Nigel , Polkinghorne Kevan R. , Wolfe Rory , Ryan Joanne
Published: November 2023

Introduction:

In healthy older adults, the relationship between long-term, visit-to-visit variability in blood pressure (BP) and frailty is uncertain.

Methods:

Secondary analysis of blood pressure variability (BPV) and incident frailty in >13 000 participants ≥65–70 years enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial and its observational follow-up (ASPREE-XT). Participants were without dementia, physical disability, or cardiovascular disease at baseline. BPV was estimated using standard deviation of mean BP from three annual visits (baseline through the second annual follow-up). Frailty was defined using Fried phenotype and a frailty deficit accumulation index (FDAI). Participants with frailty during the BPV estimation period were excluded from the main analysis. Adjusted Cox proportional hazards regression evaluated the association between BPV and incident frailty, and linear mixed models for change in frailty scores, through a maximum of 9 years of follow-up.

Results:

Participants in the highest systolic BPV tertile were at higher risk of frailty compared to those in the lowest (referent) tertile of systolic BPV [Fried hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.04–1.31; FDAI HR 1.18, 95% CI 1.07–1.30]. Findings were consistent when adjusted for multiple covariates and when stratified by antihypertensive use. Linear mixed models showed that higher systolic BPV was associated with increasing frailty score over time. Diastolic BPV was not consistently associated.

Conclusions:

High systolic BPV, independent of mean BP, is associated with increased risk of frailty in healthy older adults. Variability of BP across visits, even in healthy older adults, can convey important risk information beyond mean BP.

Trial Registration:

ClinicalTrials.gov NCT01038583 and ISRCTN83772183
Role of the Electrocardiographic MVP Risk Score (Morphology-Voltage-P Wave Duration) in Predicting the Development of Atrial Fibrillation in Patients With Systemic Arterial Hypertension
Authors: del Pilar Falcón Rocío , Centurión Osmar Antonio , Meza Alfredo J. , Scavenius Karina E. , Chávez Christian O. , Montiel Carmen R. , García Laura B. , Cáceres Cristina , Martínez Jorge E. , Galeano Erdulfo J.
Published: November 2023

Background:

There is a global tendency to emphasize the prevention and early diagnosis of diseases that have a great impact on public health. Atrial fibrillation (AF) has a prevalence affecting 1.5–2% of the general population. Certain variables of the P wave allow us to identify and stratify patients at risk of developing AF.

Materials and methods:

This is an observational, descriptive, and longitudinal study to determine the applicability of the electrocardiographic (ECG) morphology, voltage, and P wave duration (MVP) risk score to predict the development of AF in consecutive patients with systemic hypertension (SH) in an initial follow-up of 12 months.

Results:

Initially, 104 patients were included, of whom 12 died during follow-up and 17 did not attend subsequent checkups during the COVID-19 pandemic; therefore, they were excluded. The study patients were 75, of whom AF was detected in 25 patients (33%). The average duration of the P wave was 120 ± 26 ms, the average voltage was 0.1 ± 0.5 Mv. The high-risk MVP ECG score had an [area under the curve, 0.69; 95% confidence intervals (CI), 0.59–0.79] and demonstrated a specificity and a positive predictive value of 100%, a negative predictive value of 76%, and a sensitivity of 40% for predicting the development of AF.

Conclusions:

The present study establishes for the first time that SH patients who possess a high-risk MVP ECG score have a significantly higher incidence of developing AF. The high-risk MVP Score has a specificity and a positive predictive value of 100% and a high negative predictive value with a moderate sensitivity for the prediction of the development of AF in SH patients.
Overweight (BMI of 25–30) Is Independently Associated With Significantly Higher Prevalence of Systolic and Diastolic Hypertension in Adults
Authors: Movahed Mohammad Reza , Motieian Mahsa , Bates Sharon
Published: November 2023

Objective:

Hypertension (HTN) is a major risk factor for cardiovascular disease. Obesity has been found to be associated with HTN. However, there are not many studies available to evaluate any association between overweight alone and HTN.

Methods:

A database from the Anthony Bates Foundation that performs preventive cardiovascular examinations including measurement of body mass index (BMI) and blood pressure across the United States was used for our study. Using recorded measurements, we evaluated any association between being overweight defined as a BMI of 25 to 30 and the occurrence of systolic and diastolic HTN in adults over the age of 18 years.

Results:

A total of 1558 participants with documented BMI and blood pressure over the age of 18 years were studied. Among them, 758 participants had a normal BMI, and 800 had a BMI in overweight category. The prevalence of systolic and diastolic HTN was significantly higher in participants in the overweight versus normal weight cohort. Systolic HTN was present in 36% of participants in the overweight versus 14% of the normal weight group (P < 0.00.1). Diastolic HTN was present in 43% of participants with overweight versus 21% of normal weight cohort (P < 0.001). After adjusting for age and gender, high systolic blood pressure (SBP) and diastolic blood pressure (DBP) remained independently associated with overweight (SBP prevalence OR, 2.8; CI, 2.1-3.6; P < 0.001; DBP prevalence OR, 2.1; CI, 1.7-2.7; P < 0.001)

Conclusions:

Our study found that increased BMI in the overweight category alone is independently associated with SBP and DBP in adults undergoing screening warranting further investigation.
The Use of Global Longitudinal Strain to Detect Subclinical Reduction in Left Ventricular Pump Function
Authors: EL-Dosouky Ibtesam I. , Seddik Eman H. , Wageeh Shaimaa
Published: November 2023

Background:

Left ventricular (LV) ejection fraction (LVEF) is not a sensitive marker of LV systolic function in a subset of patients with preserved EF. The relation between LV pump function and global longitudinal strain (GLS) has not been elucidated well in patients with objectively preserved EF and no apparent heart failure (HF). We aimed to detect whether LV GLS can discover impaired LV pump function [presented as low stroke volume index (SVI) and low cardiac output (COP)] in patients with objectively preserved EF and no apparent clinical HF and its practice utility.

Methods:

In total, 100 participants with LVEF of ≥50% were studied for demographic and echocardiographic data, including LVEF, stroke volume, SVI, COP, LV longitudinal strain assessments, apical 4-, 3-, and 2-chamber views averaged for GLS, and were classified into 2 groups: group 1: normal GLS (more negative than −18%) and group 2: low GLS (less negative than −18%).

Results:

Reduced LV GLS was associated with lower SVI (35.6 ± 13.6 vs. 43.8 ± 12.7 mL/m2; P = 0.01), lesser COP (5.4 ± 1.9 vs. 6.5 ± 2.1 l/min; P = 0.02), GLS had strong positive correlations with SVI (r = 0.75; P < 0.001), and COP (r = 0.66; P < 0.001). LV GLS at a cutoff value less negative than −15% is a strong predictor of SVI ≤35 mL/m2 (76% sensitivity and 79% specificity) and at a cutoff value less negative than −13.5% it is a strong predictor of COP ≤4 L/min (76% sensitivity and 73% specificity). LV GLS was the best independent predictor of low SVI (<35 mL/m2) and low COP (<4 L/min).

Conclusion:

Impaired LV strain is associated with lower LV pump function, presented as lower COP and lower SVI in patients with preserved EF even in the absence of clinical HF. It is of great importance to incorporate GLS in the routine evaluation of LV function hand-by-hand with the noninvasive assessment of LV stroke volume and COP that can replace GLS on evaluation of LV pump function in old machines with no GLS modalities, for early pick-up of patients with impaired LV pump function before apparent HF.