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1.
mBio ; 15(5): e0069324, 2024 May 08.
Article En | MEDLINE | ID: mdl-38587426

Among genes present in all group A streptococci (GAS), those encoding M-fibril and T-pilus proteins display the highest levels of sequence diversity, giving rise to the two primary serological typing schemes historically used to define strain. A new genotyping scheme for the pilin adhesin and backbone genes is developed and, when combined with emm typing, provides an account of the global GAS strain population. Cluster analysis based on nucleotide sequence similarity assigns most T-serotypes to discrete pilin backbone sequence clusters, yet the established T-types correspond to only half the clusters. The major pilin adhesin and backbone sequence clusters yield 98 unique combinations, defined as "pilin types." Numerous horizontal transfer events that involve pilin or emm genes generate extensive antigenic and functional diversity on the bacterial cell surface and lead to the emergence of new strains. Inferred pilin genotypes applied to a meta-analysis of global population-based collections of pharyngitis and impetigo isolates reveal highly significant associations between pilin genotypes and GAS infection at distinct ecological niches, consistent with a role for pilin gene products in adaptive evolution. Integration of emm and pilin typing into open-access online tools (pubmlst.org) ensures broad utility for end-users wanting to determine the architecture of M-fibril and T-pilus genes from genome assemblies.IMPORTANCEPrecision in defining the variant forms of infectious agents is critical to understanding their population biology and the epidemiology of associated diseases. Group A Streptococcus (GAS) is a global pathogen that causes a wide range of diseases and displays a highly diverse cell surface due to the antigenic heterogeneity of M-fibril and T-pilus proteins which also act as virulence factors of varied functions. emm genotyping is well-established and highly utilized, but there is no counterpart for pilin genes. A global GAS collection provides the basis for a comprehensive pilin typing scheme, and online tools for determining emm and pilin genotypes are developed. Application of these tools reveals the expansion of structural-functional diversity among GAS via horizontal gene transfer, as evidenced by unique combinations of surface protein genes. Pilin and emm genotype correlations with superficial throat vs skin infection provide new insights on the molecular determinants underlying key ecological and epidemiological trends.


Genetic Variation , Genotype , Streptococcus pyogenes , Streptococcus pyogenes/genetics , Streptococcus pyogenes/classification , Humans , Recombination, Genetic , Bacterial Outer Membrane Proteins/genetics , Fimbriae Proteins/genetics , Gene Transfer, Horizontal , Antigens, Bacterial/genetics , Streptococcal Infections/microbiology , Streptococcal Infections/epidemiology , Impetigo/microbiology , Impetigo/epidemiology , Pharyngitis/microbiology , Fimbriae, Bacterial/genetics , Carrier Proteins
2.
J Vasc Surg ; 2024 Apr 09.
Article En | MEDLINE | ID: mdl-38604320

OBJECTIVE: Failure to achieve timely arteriovenous fistulae (AVFs) utilization due to excessive depth (>6 mm) remains an ongoing concern for dialysis access. This study evaluates the outcomes of radiocephalic (RCF) and brachiocephalic (BCF) fistula elevation required for access utilization. METHODS: A retrospective review of all patients undergoing first-time autologous access over 10 years was undertaken. RCF and BCF were analyzed, and cases of initial access failure due to depth alone were selected for study. Primary and staged brachio-basilic AVF were excluded. Outcomes of early thrombosis, line placement, maturation (successful progression to hemodialysis [HD∖), reintervention, and functional dialysis (continuous HD for 3 consecutive months) were examined. RESULTS: From January 2012 to December 2022, 1733 patients (67% female; mean age, 61 ± 14 years) underwent autologous AVF placement. Of these, 298 patients (17%) had depth-related AVF access issues (BCF, 71% and RCF, 29%). Nineteen percent of these AVFs underwent a primary balloon-assisted maturation (BAM), and 2% had side branch coil embolization before consideration for elevation. The average time to intervention for depth was 11 ± 4 weeks after primary creation. During elevation, side branch ligation occurred in 38% of cases, and 15% underwent intraoperative BAM, The pre-elevation depth was 8.2 ± 3.1 mm, and the mean post-elevation depth was 4.7 ± 2.9 mm (P = .002). Early thrombosis (<18 days) occurred in 4% of cases. There was no mortality, and the 30-day major adverse cardiac event rate was 2%, with a 30-day morbidity of 5%, which was driven by wound issues. Six percent of the AVFs underwent follow-up BAM within 3 months. Mean maturation of the AVFs was 74% ± 3% vs 72% ± 3% (P = .58) for the elevation vs no-elevation groups at 24 weeks, respectively. However, there was an increase in tunneled central line placement in pre-emptive fistula patients due to the delay in maturation (elevation, 17% vs no-elevation, 8%; P = .008). There was a mean successful access time of 6 ± 3 weeks after elevation (16 ± 4 weeks after access creation). There was a median of 2.4 secondary interventions per year after elevation compared with a median of 2.7 secondary interventions per year without elevation. Mean access functionality was 68% ± 8% vs 75% ± 8% at 3 years for the elevation vs no-elevation groups, respectively (P = .25). CONCLUSIONS: Elevation of deep BCF and RCF occurs late after placement but can be successfully achieved with low morbidity and satisfactory long-term functionality. It results in an increase in tunneled central line placement in pre-emptive fistula patients. Elevation is a valuable adjunct to AVF maturation and enhances an autologous access policy.

3.
J Vasc Surg ; 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38649103

BACKGROUND: Infra-malleolar disease is present in most diabetic patients presenting with tissue loss. Infra-malleolar (pedal) artery disease and pedal medial arterial calcification (pMAC) are associated with major amputation in patients with chronic limb-threatening ischemia (CLTI). This study aimed to examine the impact of pMAC on the outcomes after isolated infra-malleolar (pedal artery) interventions. METHODS: A database of lower extremity endovascular intervention for tissue loss patients between 2007 and 2022 was retrospectively queried. Patients with CLTI were selected, and those undergoing isolated infra-malleolar intervention on the dorsalis pedis and medial and lateral tarsal arteries and who had foot x-rays were identified. X-rays were assessed blindly for pMAC and scored on a scale of 0-5. Patients with concomitant superficial femoral artery (SFA) and tibial interventions were excluded. Intention to treat analysis by the patient was performed. Amputation-free survival (AFS; survival without major amputation) was evaluated. RESULTS: 223 patients (51% female, 87% Hispanic, average age 66 years; 323 vessels) underwent isolated infra-malleolar intervention for tissue loss. All patients had diabetes, 96% had hypertension, 79% had hyperlipidemia, and 63% had chronic renal insufficiency (55% of these were on hemodialysis). Most of the patients had WIfI stage 3 disease and had various stages of pMAC: severe (score=5) in 48%, moderate (score = 2-4) in 31%, and mild (score = 0-1) in 21% of the patients. Technical success was 94%, with a median of 1 vessel treated per patient. All failures were in severe pMAC. Overall, Major Adverse Cardiovascular Events (MACE) was 0.9% at 90 days after the procedure. Following the intervention, most patients underwent a planned forefoot amputation (single digit, multiple digits, ray amputation, or trans-metatarsal amputation). WIfI ischemic grade was improved by 51%. Wound healing at three months was 69%. Those not healing underwent below-knee amputations (BKA). The overall 5-yr-AFS rate was 35±9%. The severity of pMAC was associated with decreased AFS. CONCLUSIONS: PMAC influences the technical and long-term outcomes of Infra-malleolar intervention in diabetes. Severe pMAC is associated with amputation and should be considered as a variable in the shared decision-making of diabetic patients with CLTI.

4.
Hip Int ; : 11207000241241288, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38566283

BACKGROUND: Hip transposition surgery after surgical resection of large pelvic tumours is a well-established alternate to endoprosthetic reconstruction. The major goals of surgery are to ensure adequate resection margins with limb salvation, albeit with acceptable levels of morbidity. While surveillance is aimed at diagnosing local recurrence or distant metastasis primarily, other complications may occasionally be seen.The aim of this study was to assess incidence of avascular necrosis (AVN) in the preserved native femoral heads after hip transposition surgery for periacetabular malignancies, also known as hanging hip surgery. PATIENTS AND METHODS: Patient records and follow-up imaging of 22 patients who had undergone hanging hip surgery from 1999 to 2020 were retrospectively analysed to assess for any probable causes of AVN. RESULTS: Of the 22 patients, 5 (22.7%) had developed AVN on follow-up with a mean time of onset of about 10.5 months from surgery (5 months-2 years). A review of the patient demographics, surgical notes, preoperative management did not offer any clues as to the cause of AVN in these patients. Osteopenia was the most common radiological finding (59%) in most patients, but this also did not herald AVN onset. CONCLUSIONS: The theory that loss of major vascular supply to the femoral head from capsular disruption during hip transposition surgery would lead to AVN in most patients did not hold true as AVN occurred in a small number of patients.

5.
Nat Commun ; 15(1): 3477, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38658529

Streptococcus dysgalactiae subspecies equisimilis (SDSE) and Streptococcus pyogenes share skin and throat niches with extensive genomic homology and horizontal gene transfer (HGT) possibly underlying shared disease phenotypes. It is unknown if cross-species transmission interaction occurs. Here, we conduct a genomic analysis of a longitudinal household survey in remote Australian First Nations communities for patterns of cross-species transmission interaction and HGT. Collected from 4547 person-consultations, we analyse 294 SDSE and 315 S. pyogenes genomes. We find SDSE and S. pyogenes transmission intersects extensively among households and show that patterns of co-occurrence and transmission links are consistent with independent transmission without inter-species interference. We identify at least one of three near-identical cross-species mobile genetic elements (MGEs) carrying antimicrobial resistance or streptodornase virulence genes in 55 (19%) SDSE and 23 (7%) S. pyogenes isolates. These findings demonstrate co-circulation of both pathogens and HGT in communities with a high burden of streptococcal disease, supporting a need to integrate SDSE and S. pyogenes surveillance and control efforts.


Gene Transfer, Horizontal , Interspersed Repetitive Sequences , Streptococcal Infections , Streptococcus pyogenes , Streptococcus , Streptococcus pyogenes/genetics , Streptococcus pyogenes/isolation & purification , Streptococcus pyogenes/classification , Streptococcal Infections/transmission , Streptococcal Infections/microbiology , Humans , Streptococcus/genetics , Streptococcus/isolation & purification , Interspersed Repetitive Sequences/genetics , Australia , Genome, Bacterial/genetics , Female , Male , Child , Family Characteristics , Adult , Child, Preschool , Adolescent , Longitudinal Studies , Drug Resistance, Bacterial/genetics , Young Adult
6.
Ann Vasc Surg ; 105: 287-306, 2024 Apr 06.
Article En | MEDLINE | ID: mdl-38588954

BACKGROUND: Massive pulmonary embolism (MPE) carries significant 30-day mortality risk, and a change in societal guidelines has promoted the increasing use of extracorporeal membrane oxygenation (ECMO) in the immediate management of MPE-associated cardiovascular shock. This narrative review examines the current status of ECMO in MPE. METHODS: A literature review was performed from 1982 to 2022 searching for the terms "Pulmonary embolism" and "ECMO," and the search was refined by examining those publications that covered MPE. RESULTS: In the patient with MPE, veno-arterial ECMO is now recommended as a bridge to interventional therapy. It can reliably decrease right ventricular overload, improve RV function, and allow hemodynamic stability and restoration of tissue oxygenation. The use of ECMO in MPE has been associated with lower mortality in registry reviews, but there has been no significant difference in outcomes between patients treated with and without ECMO in meta-analyses. Applying ECMO is also associated with substantial multisystem morbidity due to systemic inflammatory response, bleeding with coagulopathy, hemorrhagic stroke, renal dysfunction, and acute limb ischemia, which must be factored into the outcomes. CONCLUSIONS: The application of ECMO in MPE should be combined with an aggressive interventional pulmonary interventional program and should strictly adhere to the current selection criteria.

7.
Nature ; 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38588696

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer1,2, who were germline BRCA1 and BRCA2 wild type3. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)4, and secondary end points included event-free survival (EFS) and overall survival (OS)5. pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .

8.
Nat Commun ; 15(1): 2286, 2024 Mar 13.
Article En | MEDLINE | ID: mdl-38480728

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.


Streptococcal Infections , Streptococcus , Vaccines , Humans , Streptococcus pyogenes/genetics , Gene Flow
9.
Front Surg ; 11: 1302568, 2024.
Article En | MEDLINE | ID: mdl-38440414

Approximately 3% of all patients presenting with Thoracic Outlet Syndrome have a venous etiology (vTOS), which is considered "effort thrombosis". These patients will present with symptomatic deep venous thrombosis or focal subclavian vein (SCV) stenosis. Endovascular management of vTOS occurs in several phases: diagnostic, preoperative therapeutic intervention before decompression, postoperative interventions after decompression, and delayed interventions in the follow-up after decompression. In the diagnostic phase, dynamic SCV venography can establish functional vTOS. Approximately 4,000 patients have been treated for vTOS and reported in the literature since 1970. Declotting of the SCV was followed by surgical decompression in 53% of patients, while in the remainder, surgical decompression alone (18%), endovascular intervention alone (15%), or conservative therapy with anticoagulation (15%) was performed. The initial intervention was predominantly catheter-directed thrombolysis, with <10% of cases undergoing concomitant balloon angioplasty. 93% of cases were successful. In the postoperative phase, balloon angioplasty was performed to correct residual intrinsic SCV disease after vTOS decompression in under 15% of cases. Stents were rarely deployed. Symptom relief was reported as 94 ± 12% (mean ± SD) and 90 ± 23%, respectively for declotting with decompression and declotting alone. In the delayed phase, balloon angioplasty was performed in under 15% of cases to re-establish patency.

10.
Diabetes Obes Metab ; 26(4): 1464-1478, 2024 Apr.
Article En | MEDLINE | ID: mdl-38312024

AIM: Obesity has a significant impact on all-cause mortality rate and overall health care resource use (HCRU). These outcomes are also strongly linked to age, sex and local deprivation of the population. We aimed to establish the lifetime costs of obesity by demographic group/geographic area using published mortality rates and HCRU use for integrated care boards (ICB) in England in the context of costs of therapeutic intervention. METHODS: Population and expected mortality rates by age, sex and deprivation were obtained from national data. Obesity class prevalence was taken from the health of the nation study. The published impact of obesity by age, group, sex and deprivation on mortality and HCRU were applied to estimate life years lost and lifetime HCRU [by sex, age band and body mass index (BMI) class for each ICB]. The year 2019 was chosen as the study basis data to avoid influences of COVID-19 pandemic on obesity rates with application of 2022/23 HCRU values. Outcomes including prevalence, deaths, life years lost, HCRU and lifetime HCRU were compared by age and sex groups across four BMI classes normal/underweight (BMI <25 kg/m2 ), overweight (25-29.9 kg/m2 ), obese class I and II (30-39.9 kg/m2 ), and obese class III (≥40), with benchmarking being set against all population being BMI <25 kg/m2 overall and by each of the 42 ICBs. We also associated future life with deaths to provide an estimate of 'future life years lost' occurring each year. RESULTS: Total population aged >16 years was 45.4 million (51% female). PREVALENCE: 13.7 million (28% of the total adult population) had a BMI ≥30 mg/m2 and BMI ≥40 kg/m2 were 1.50 million (12%) of these 1.0 million (68%) were female and of these 0.6 million 40% were women aged 16-49 years. In addition, 35% of those with a BMI ≥40 kg/m2 were in the top deprivation quintile (i.e. overall 20%). Mortality was based on expected deaths of 518K/year, and modelling suggested that if a BMI <25 kg/m2 was achieved in all individuals, the death rate would fall by 63K to 455K/year for the English population (12% reduction). For those with a BMI ≥40 kg/m2 the predicted reduction was 12K deaths (54% lower); while in those aged 16-49 years with a BMI ≥40 kg/m2 72% of deaths were linked to obesity. For future life years lost, we estimated 2.5 years were lost in people with BMI 30-39.9 kg/m2 6.7 years when BMI ≥40 kg/m2 . However, for those aged 16-49 years with a BMI ≥40 kg/m2 , 8.3 years were lost. HCRU, for weight reduction, the annual HCRU decrease from BMI ≥40 kg/m2 to BMI 30-39.9 kg/m2 was £342 per person and from BMI 30-39.9 to 25-29.9 kg/m2 the reduction was £316/person. However, lifetime costs were similar because of reduced life expectancy for obese individuals. In quality adjusted life years (QALY), overall, 791 689 future life years were lost (13.1% of all) in people with BMI ≥25 kg/m2 and were related to excess weight. When the NICE £30 000 per QALY value was applied to the estimated total 791 689 future life years lost then the potential QALY value reduction lost was equivalent to £24 billion/year or £522/person in the obese population. For morbidly obese men and women the potential QALY value lost was £2864/person/year. Regarding geography, across the 42 ICBs, we observed significant variation in the prevalence of BMI ≥40 (1.8%-4.3%), excess mortality (11.6%-15.4%) and HCRU linked to higher BMI (7.2%-8.8%). The areas with the greatest impact on HCRU were in the north-west, north-east and Midlands of England, while the south shows less impact. CONCLUSION: The expected increases in annual HCRU because of obesity, when considered over a lifetime, are being mitigated by the increased mortality of obese individuals. Our data suggest that simple short-term HCRU reduction brought about through BMI reduction will be insufficient to fund additional specialist weight reduction interventions. The HRCUs associated with BMI are not in most cases related to short-term health conditions. They are a cumulative result over a number of years, so for age 16-49 years reducing BMI from ≥40 to 30-39.9 kg/m2 might show an annual decrease in HCRU/person by £325/year for women and £80/year for men but this might not have immediately occurred within that year. For those aged >70 years reducing BMI from ≥40 to 30-39.9 kg/m2 might show an annual decrease in HCRU/person by £777/year for women and £796/year for men but also may not be manifest within that year. However, for the morbidly obese men and women, the potential QALY value lost was £2864 per person per year with the potential for these funds to be applied to intensive weight management programmes, including pharmacotherapy.


Obesity, Morbid , Adult , Male , Humans , Female , Obesity, Morbid/complications , Pandemics , Quality-Adjusted Life Years , England/epidemiology , Weight Loss
11.
Value Health ; 27(3): 313-321, 2024 03.
Article En | MEDLINE | ID: mdl-38191024

OBJECTIVE: This study aimed to measure the value of increasing lung cancer screening rates for high-risk individuals and its impact on health disparities. METHODS: The model estimated changes in health economic outcomes if low-dose computed tomography screening increased from current to 100% compliance, following clinical guidelines. Current low-dose computed tomography screening rates were estimated by income, education, and race, using 2017-2019 Behavioral Risk Factor Surveillance System data. The model contained a decision tree module to segment the population by screening outcomes and a Markov chain module to estimate cancer progression over time. Model parameters included information on survival, quality of life, and costs related to cancer diagnosis, treatment, and adverse events. Distributional cost-effectiveness analysis estimated the net monetary value from reduced health disparities-measured using quality-adjusted life expectancy-across income, education, and race groups. Outcomes were assessed over 30 years. RESULTS: Lung cancer screening eligibility using US Preventive Services Task Force guidelines was higher for individuals with income <$15 000 (47.2%) and without a high-school education (46.1%) than individuals with income >$50 000 (16.6%) and with a college degree (13.5%), respectively. Increasing lung cancer screening to 100% compliance was cost-effective ($64 654 per quality-adjusted life-year) and produced economic value by up to $560 per person ($182.1 billion for United States overall). Up to 32.2% of the value was due to reductions in health disparities. CONCLUSIONS: Significant value in increasing lung cancer screening rates derived from reducing health disparities. Policy makers and clinicians may not be appropriately prioritizing cancer screening if value from reducing health disparities is unconsidered.


Early Detection of Cancer , Lung Neoplasms , Humans , United States , Quality of Life , Mass Screening , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/epidemiology , Cost-Benefit Analysis , Tomography, X-Ray Computed/methods , Health Inequities
12.
Open Forum Infect Dis ; 11(1): ofae001, 2024 Jan.
Article En | MEDLINE | ID: mdl-38250201

Background: We report clinical, epidemiological, and laboratory features of a large diarrhea outbreak caused by a novel Cryptosporidium hominis subtype during British military training in Kenya between February and April 2022. Methods: Data were collated from diarrhea cases, and fecal samples were analyzed on site using the multiplex polymerase chain reaction (PCR) BioFire FilmArray. Water was tested using Colilert kits (IDEXX, UK). DNA was extracted from feces for molecular characterization of Cryptosporidium A135, Lib13, ssu rRNA, and gp60 genes. Results: One hundred seventy-two of 1200 (14.3%) personnel at risk developed diarrhea over 69 days. One hundred six primary fecal samples were tested, and 63/106 (59.4%; 95% CI, 0.49%-0.69%) were positive for Cryptosporidium spp. Thirty-eight had Cryptosporidium spp. alone, and 25 had Cryptosporidium spp. with ≥1 other pathogen. A further 27/106 (25.5%; 95% CI, 0.18%-0.35%) had non-Cryptosporidium pathogens only, and 16/106 (15.1%; 95% CI, 0.09%-0.23%) were negative. C. hominis was detected in 58/63 (92.1%) Cryptosporidium spp.-positive primary samples, but the others were not genotypable. Twenty-seven C. hominis specimens were subtypable; 1 was gp60 subtype IeA11G3T3, and 26 were an unusual subtype, ImA13G1 (GenBank accession OP699729), supporting epidemiological evidence suggesting a point source outbreak from contaminated swimming water. Diarrhea persisted for a mean (SD) of 7.6 (4.6) days in Cryptosporidium spp. cases compared with 2.3 (0.9) days in non-Cryptosporidium cases (P = .001). Conclusions: Real-time multiplex PCR fecal testing was vital in managing this large cryptosporidiosis outbreak. The etiology of a rare C. hominis gp60 subtype emphasizes the need for more genotypic surveillance to identify widening host and geographic ranges of novel C. hominis subtypes.

13.
J Biol Chem ; 300(2): 105623, 2024 Feb.
Article En | MEDLINE | ID: mdl-38176650

Group A Streptococcal M-related proteins (Mrps) are dimeric α-helical-coiled-coil cell membrane-bound surface proteins. During infection, Mrp recruit the fragment crystallizable region of human immunoglobulin G via their A-repeat regions to the bacterial surface, conferring upon the bacteria enhanced phagocytosis resistance and augmented growth in human blood. However, Mrps show a high degree of sequence diversity, and it is currently not known whether this diversity affects the Mrp-IgG interaction. Herein, we report that diverse Mrps all bind human IgG subclasses with nanomolar affinity, with differences in affinity which ranged from 3.7 to 11.1 nM for mixed IgG. Using surface plasmon resonance, we confirmed Mrps display preferential IgG-subclass binding. All Mrps were found to have a significantly weaker affinity for IgG3 (p < 0.05) compared to all other IgG subclasses. Furthermore, plasma pulldown assays analyzed via Western blotting revealed that all Mrp were able to bind IgG in the presence of other serum proteins at both 25 °C and 37 °C. Finally, we report that dimeric Mrps bind to IgG with a 1:1 stoichiometry, enhancing our understanding of this important host-pathogen interaction.


Bacterial Proteins , Streptococcus pyogenes , Humans , Bacterial Outer Membrane Proteins/metabolism , Bacterial Proteins/metabolism , Carrier Proteins/metabolism , Immunoglobulin G/metabolism , Streptococcus pyogenes/metabolism
14.
Phlebology ; 39(1): 58-65, 2024 Feb.
Article En | MEDLINE | ID: mdl-37902613

OBJECTIVE: YouTube® has gained popularity as an unofficial educational resource for surgical trainees, but its content's quality and educational value remain to be evaluated. The aim of this study is to analyze the current content on these techniques for lower extremity DVT (LEDVT) on YouTube®. METHODS: A search was performed on YouTube® using 13 search terms in August 2022 on a clear-cached browser. Open-access videos focusing on the surgical techniques of venous thrombolysis or thrombectomy for LEDVT were included. Quality and educational value were assessed and graded based on metrics for accountability (4 items), content (13 items), and production (9 items). RESULTS: Out of 138 videos regarding LEDVT oriented towards medical professionals, only 14 met inclusion criteria. Videos ran for a median of 3.4 min (range 0.37-35.6 min) with a median of 941 views (range 106-54624). Videos scored a median of 5.5 (range 1.0-8.0) out of 11 for content, a median of 2.0 out of 6.0 (range 0.0-2.0) for accountability, and a median of 5.5 out of 9.0 (range 3.0-9.0) for production. CONCLUSION: Few YouTube® videos focus on the technical aspects of DVT thrombolysis/thrombectomy, and they vary significantly in content with overall poor accountability and production quality.


Social Media , Venous Thrombosis , Humans , Video Recording/methods , Veins , Venous Thrombosis/therapy , Thrombolytic Therapy
15.
Am Surg ; 90(4): 682-690, 2024 Apr.
Article En | MEDLINE | ID: mdl-37853701

BACKGROUND: One-third of American adults encompassed by current colorectal cancer screening guidelines fail to obtain recommended screening evaluations. Educational videos are a valuable medium through which to educate and encourage recommended health behaviors in patients. METHODS: A cross-sectional study reviewing the quality of patient education videos addressing colorectal cancer screening. Video quality was assessed in 3 domains: accountability, content, and production. RESULTS: Forty-four videos met inclusion criteria. Out of 33 possible points, videos scored a median of 15.0 (interquartile range 12.9-16.6). Videos scored 1.0 (interquartile range .8-1.0) out of 4.0 for accountability, 6.0 (interquartile range 4.4-8.0) out of 20 for content, and 8.0 (interquartile range 7.4-8.0) out of 9.0 for production. Colonoscopy was the most frequently discussed method of screening (38, 86%). While 13 (34%) videos discussed the risk of colorectal cancer in the general population and 15 (32%) discussed the risk in those with a family history, few videos addressed those with other risk factors. Most (31, 70%) videos discussed the medical consequences of not receiving screening, but only 1 (2%) video discussed the social consequences. Similarly, medical benefits were discussed in 34 (77%) videos while other benefits were not discussed by any video. Only one-fifth of the videos address three or more barriers to screening. CONCLUSIONS: Videos on colorectal cancer screening have excellent production quality but need improvement in the domains of accountability and content. The videos included in this analysis did not adequately address the concerns of viewers nor the benefits of colorectal cancer screening.


Colorectal Neoplasms , Social Media , Humans , United States , Early Detection of Cancer , Cross-Sectional Studies , Video Recording/methods , Colorectal Neoplasms/diagnosis
16.
J Vasc Surg ; 79(3): 662-670.e3, 2024 Mar.
Article En | MEDLINE | ID: mdl-37925041

OBJECTIVE: Maintenance of long-term arteriovenous access is important in long-term care for patients with end-stage renal disease. Arteriovenous access is associated in the long term with the development of fistula aneurysms (FAs). This study aims to evaluate the outcomes of staged FA treatment in dialysis access arteriovenous fistulae (AVF). METHODS: A retrospective review of all patients over a 12-year period with primary autogenous AVF was undertaken at a single center. Patients undergoing elective open aneurysm repair were identified and were categorized into three groups: single FA repair (single, control group) and staged and unstaged repair of two FAs (staged and unstaged). A staged repair was a procedure in which the initial intent was to treat both aneurysms in the AVF and in which the most symptomatic aneurysm was treated first. When the incision from the first surgery had healed, the second symptomatic aneurysm in the AVF was treated. An unstaged repair was a procedure in which the initial intent was to repair both symptomatic aneurysms simultaneously. All patients had a fistulogram before the FA repair. Thirty-day outcomes, cannulation failure, line placement, reintervention, and functional dialysis (continuous hemodialysis for 3 consecutive months) were examined. RESULTS: Five hundred twenty-seven patients presented with FA that met requirements for open intervention; 44% underwent single FA repair, whereas the remaining 34% and 22% underwent staged and unstaged repair of two FAs, respectively. The majority of patients were diabetic and Hispanic. Ninety-one percent of the patients required percutaneous interventions of the outflow tract (37%) and the central veins (54%). Thirty-day major adverse cardiovascular events were equivalent across all modalities. Thirty-day morbidity and early thrombosis (<18 days) were significantly higher in the unstaged group (4.3%) compared with the two other groups (1.3% and 2.1%, single and staged, respectively), which led to an increased need for a short-term tunneled catheter (8.9%) compared with the two other groups (3.4% and 4.4%, single and staged, respectively), Unstaged repair resulted in an increased incidence of secondary procedures (5.0%) compared with the two other groups (2.6% and 3.1%, single and staged, respectively). Functional dialysis at 5 years was equivalent in the single and staged groups but was significantly decreased in the unstaged group. CONCLUSIONS: Open interventions are successful therapeutic modalities for FAs, but unstaged rather than staged repair of two concurrent FAs results in a higher early thrombosis, an increased secondary intervention rate, and a need for a short-term tunneled central line. Staged and single FA repairs have equivalent results. In the setting of two symptomatic FAs, staged repair is recommended.


Aneurysm , Arteriovenous Fistula , Arteriovenous Shunt, Surgical , Thrombosis , Humans , Arteriovenous Shunt, Surgical/adverse effects , Treatment Outcome , Veins/diagnostic imaging , Veins/surgery , Aneurysm/diagnostic imaging , Aneurysm/etiology , Aneurysm/surgery , Arteriovenous Fistula/complications , Renal Dialysis/adverse effects , Thrombosis/etiology , Retrospective Studies , Vascular Patency
17.
Ann Vasc Surg ; 100: 233-242, 2024 Mar.
Article En | MEDLINE | ID: mdl-38122974

BACKGROUND: Arteriovenous accesses develop aneurysms (FA) during their active use, resulting in pain, erosion, bleeding, and difficulty in cannulation. This study aims to evaluate the outcomes of open and endovascular management of single FA in arteriovenous fistulas (AVF). METHODS: A retrospective review of all upper extremity primary AVFs over 12 years was undertaken at a single center. Patients undergoing elective open and endovascular repair of a single FA were identified. Thirty-day outcomes, cannulation failure, line placement, re-intervention, and functional dialysis (continuous hemodialysis) for 3 consecutive months were examined. RESULTS: Three hundred and seventy nine patients presented with a single FA that met the requirements for intervention: 126 (33%) underwent endovascular repair, and the remainder 253 (67%) underwent open repair. Preoperative fistulogram identified anatomically significant issues in 91% of the cases, and these were treated by balloon angioplasty: 10% within the fistula tract, 44% within the outflow tract, and 47% in the central veins. In open repair, 57% underwent plication, 35% underwent resection and re-anastomosis, and the remainder (8%) underwent interposition grafting. In endovascular repair, successful placement of a stent was achieved in all cases with 1 ± 2 (mean ± standard deviation [SD]) covered stents (diameter: 6 -8 mm) placed, achieving successful exclusion of the FA. The combination of early thrombosis and cannulation failures led to the greater need for a tunneled central line in endovascular repair (6.5% vs. 2.4%; endovascular versus open repair; P = 0.04). As a result, the mean time for establishing renewed access in the index AVF was significantly higher in endovascular repair (2 ± 3 vs. 2 ± 2 weeks, mean ± SD; endovascular open repair versus open repair; P = 0.001). In follow-up, there were more secondary interventions per year in the endovascular compared to open repair groups (3.1 vs. 1.4 secondary interventions per year; endovascular versus open repair; P = 0.04). Median functional dialysis durations were superior in the open repair (48 ± 6%, mean + standard error) compared to the endovascular repair at 5 years. (26 ± 7%; P = 0.03). CONCLUSIONS: Open repair results in a more rapid return to access use, lower need for a tunneled central line, lower secondary re-intervention rates, and superior functional dialysis durations compared to endovascular repair. Open FA repair should be considered for symptomatic single FA repairs before endovascular FA repair.


Angioplasty, Balloon , Aortic Aneurysm, Abdominal , Arteriovenous Fistula , Arteriovenous Shunt, Surgical , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Humans , Arteriovenous Shunt, Surgical/adverse effects , Endovascular Aneurysm Repair , Graft Occlusion, Vascular , Vascular Patency , Aortic Aneurysm, Abdominal/surgery , Treatment Outcome , Endovascular Procedures/adverse effects , Blood Vessel Prosthesis Implantation/adverse effects , Arteriovenous Fistula/surgery , Renal Dialysis , Retrospective Studies
18.
Eur Radiol ; 2023 Dec 07.
Article En | MEDLINE | ID: mdl-38062268

OBJECTIVES: Early, accurate diagnosis is crucial for the prognosis of patients with soft tissue sarcomas. To this end, standardization of imaging algorithms, technical requirements, and reporting is therefore a prerequisite. Since the first European Society of Musculoskeletal Radiology (ESSR) consensus in 2015, technical achievements, further insights into specific entities, and the revised WHO-classification (2020) and AJCC staging system (2017) made an update necessary. The guidelines are intended to support radiologists in their decision-making and contribute to interdisciplinary tumor board discussions. MATERIALS AND METHODS: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements were scored online by level of agreement (0 to 10) during two iterative rounds. Either "group consensus," "group agreement," or "lack of agreement" was achieved. RESULTS: Eight sections were defined that finally contained 145 statements with comments. Overall, group consensus was reached in 95.9%, and group agreement in 4.1%. This communication contains the first part consisting of the imaging algorithm for suspected soft tissue tumors, methods for local imaging, and the role of tumor centers. CONCLUSION: Ultrasound represents the initial triage imaging modality for accessible and small tumors. MRI is the modality of choice for the characterization and local staging of most soft tissue tumors. CT is indicated in special situations. In suspicious or likely malignant tumors, a specialist tumor center should be contacted for referral or teleradiologic second opinion. This should be done before performing a biopsy, without exception. CLINICAL RELEVANCE: The updated ESSR soft tissue tumor imaging guidelines aim to provide best practice expert consensus for standardized imaging, to support radiologists in their decision-making, and to improve examination comparability both in individual patients and in future studies on individualized strategies. KEY POINTS: • Ultrasound remains the best initial triage imaging modality for accessible and small suspected soft tissue tumors. • MRI is the modality of choice for the characterization and local staging of soft tissue tumors in most cases; CT is indicated in special situations. Suspicious or likely malignant tumors should undergo biopsy. • In patients with large, indeterminate or suspicious tumors, a tumor reference center should be contacted for referral or teleradiologic second opinion; this must be done before a biopsy.

19.
J Pharm Policy Pract ; 16(1): 169, 2023 Dec 21.
Article En | MEDLINE | ID: mdl-38124123

INTRODUCTION: The COVID-19 pandemic globally impacted healthcare provision. Prescribing changes in common medications can be used as a marker for new diagnoses. We describe how the prescribing of specific psychotropics was impacted by the pandemic. METHODS: Primary Care Prescribing data for different classes of drugs from March 2017 to February 2022 were considered. To capture the impact during periods of restricted access to health services for new diagnoses/existing conditions, repeat prescriptions/episodic prescribing were included with account taken of historical trends. The pre-pandemic prescriptions issued each month from March 2018 to February 2020 were linearly extrapolated forward to give an expected annual growth (EAG). The monthly average expected prescriptions for the pandemic period (March 2020-February 2022) were compared. RESULTS: Physical health medications had lower monthly prescriptions during the pandemic, most markedly for antibiotics - 12.5% (EAG - 1.3%). Bronchodilator prescribing showed a marked increase in the early pandemic months from March 2020 of 5% (EAG 0.1%). Mental health medication prescribing increased above trend for hypnotics/anxiolytics by 0.2% (EAG - 2.3%), while antidepressants fell by - 0.2% (EAG 5.0%), with no net change for antipsychotics (EAG 2.8%), but a temporary increase in antipsychotic prescribing in the early pandemic period. For all the main antidepressants prescribed in England (Sertraline, Mirtazapine, Venlafaxine, Fluoxetine and Citalopram), prescribing actually decreased in the main pandemic period vs historical trend. CONCLUSIONS: The increase in anxiolytic/hypnotic prescribing above trend links to pandemic effects on anxiety/worry. If anything, there was a slight fall in prescribing of the main antidepressants prescribed, which given prevailing circumstances at the time, suggests that access to services may have restricted access to timely assessment.

20.
J Orthop ; 44: 107-112, 2023 Oct.
Article En | MEDLINE | ID: mdl-37752985

Background: Acute Achilles tendon rupture is a common injury and when missed leads to the development of a chronic Achilles tendon rupture. Studies suggest surgical treatment (either repair or reconstruction) for most patients with a chronic Achilles rupture due to the functional deficit caused by the lack of an intact Achilles tendon. Numerous autograft options such as the flexor hallucis longus, hamstrings, peroneal and quadriceps tendon have been used to reconstruct the Achilles tendon, either as a tendon transfer or as an interposition graft. The choice of autograft used usually depends on the size of the defect left after debridement of the Achilles tendon edges, but is often dictated by surgeon preference and tissue availability. Currently, there is no consensus as to the best autograft option. Aims and methodology: The aim of this study was to evaluate the various autograft options used to reconstruct the Achilles tendon, and the advantages and disadvantages of using each tendon, focussing specifically on the harvesting technique, anatomical and biomechanical properties. This was done by reviewing the current published literature, supplemented by carrying out anatomical dissection in the cadaveric lab. Results: The flexor hallucis longus is synergistically related to the Achilles tendon and biomechanically strong, however harvesting can result in weakness in big toe flexion. The peroneus brevis whilst being biomechanically strong is a much shorter tendon compared to the other autograft options. Similarly, the quadriceps tendon is also a strong tendon option, but may not be appropriate for larger chronic Achilles tendon rupture gaps. The semitendinosus tendon can be tripled/quadrupled to resemble the Achilles tendon, but is associated with higher risks of patient morbidity when harvesting the tendon. Conclusion: Treatment of chronic Achilles tendon ruptures remains a challenge. Each autograft option has its own unique advantages and disadvantages which should be considered on a case-specific basis. Further work is required to analyse the biomechanical properties of the autograft options to determine if one option is superior.

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