Minimally Invasive Quadriceps Tendon Anterior Cruciate Ligament Reconstruction Using the Quadriceps Tendon Harvest Guide System.

Anterior cruciate ligament (ACL) reconstruction using the quadriceps tendon (QT) autograft is an increasingly utilized technique that confers less donor site morbidity and comparable outcomes to other historically used graft options. The graft harvest and implantation process present vast variability-particularly regarding the achievement of adequate graft site visualization, consistently attaining a uniform and appropriately sized graft, and subsequent reconstruction of the ACL with the all-soft tissue graft. The purpose of this Technical Note and video is to describe and demonstrate minimally invasive quadriceps tendon autograft harvesting using the Quadriceps Tendon Harvest Guide System (QUADTRAC), and its subsequent implantation within a single-bundle ACL reconstruction with suspensory fixation.

Successful treatment of stage IVB ovarian carcinosarcoma with PARP Inhibitor: A case report.

•Ovarian carcinosarcoma is a rare ovarian cancer histology that has limited treatment options.•In this study, we present an unusual association between carcinosarcoma and a STIC lesion.•In select patients with carcinosarcoma, PARP inhibition may provide clinical benefit.

Endometrial Cancer Risk Among Germline BRCA1/2 Pathogenic Variant Carriers: Review of Our Current Understanding and Next Steps.

PURPOSE: To review the literature exploring endometrial cancer (EC) risk among surgical candidates with germline BRCA1/2 pathogenic variants (PVs) to guide decisions around risk-reducing (rr) hysterectomy in this population. DESIGN: A comprehensive review was conducted of the current literature that influences clinical practice and informs expert consensus. We present our understanding of EC risk among BRCA1/2 PV carriers, the risk-modifying factors specific to this patient population, and the available research technology that may guide clinical practice in the future. Limitations of the existing literature are outlined. RESULTS: Patients with BRCA1/2 PVs, those with a personal history of tamoxifen use, those who desire long-term hormone replacement therapy, and/or have an elevated BMI are at higher risk of EC, primarily endometrioid EC and/or uterine papillary serous carcinoma, and may benefit from rr-hysterectomy. Although prescriptive clinical guidelines specific to BRCA1/2 PV carriers could inform decisions around rr-hysterectomy, limitations of the current literature prevent more definitive guidance at this time. A large population-based study of a contemporary cohort of BRCA1/2 PV carriers with lifetime follow-up compared with cancer-gene negative controls would advance this topic and facilitate care decisions. CONCLUSION: This review validates a potential role for rr-hysterectomy to address EC risk among surgical candidates with BRCA1/2 PVs. Evidence-based clinical guidelines for rr-hysterectomy in BRCA1/2 PV carriers are essential to ensure equitable access to this preventive measure, supporting insurance coverage for patients with either BRCA1 or BRCA2 PVs to pursue rr-hysterectomy. Overall, this review highlights the complexity of EC risk in BRCA1/2 PV carriers and offers a comprehensive framework to shared decision making to inform rr-hysterectomy for BRCA1/2 PV carriers.

Improving care pathways for people living with rare bone diseases (RBDs): outcomes from the first RBD Summit.

INTRODUCTION: Rare bone diseases (RBDs) are a heterogenous group of disorders that are poorly understood and challenging to treat. This creates a plethora of unmet needs for people with RBDs as well as their families and care providers, including diagnostic delays, limited access to expert care, and a lack of specialized treatments. The RBD Summit, which took place across 2 days in November 2021, was a virtual meeting of 65 RBD experts from clinical, academic, and patient communities as well as the pharmaceutical industry. The first meeting of its kind, the RBD Summit aimed to facilitate dialog and information exchange between delegates to advance knowledge and awareness of RBDs and improve patient outcomes. METHODS: Key challenges were discussed, and actions for overcoming them were proposed, including how obstacles to diagnosis can be overcome by (a) improving awareness of RBDs, (b) the implementation of a person-centered care pathway, and (c) how to narrow the communication gap between patients and healthcare professionals. RESULTS: Agreed actions were categorized as short term and long term, and priorities determined. CONCLUSION: In this position paper, we provide an overview of key discussions from the RBD Summit, summarize the subsequent action plan, and discuss the next steps in this continued collaboration.

Ureterorenoscopic stone procedures have low success rates and poor post-operative follow-up: results from an Australian tertiary health service.

BACKGROUND: To assess the results of ureterorenoscopy (URS) for upper tract urolithiasis in a contemporary Australian tertiary healthcare setting. METHODS: Hospital records of all URS stone procedures performed between January 2017 and December 2018 in a metropolitan service were retrospectively reviewed. Outcome measures including stone free rates, adherence to postoperative follow-up and complications rates were recorded. RESULTS: 385 patients (387 renal units) with mean age 53.8 (range 18-89) underwent URS for stones measuring between 2 and 27 mm (median 8 mm). 465 URS were performed with 1029 total procedures performed. 48.6% of operations were performed as day cases. Complications were recorded in 9% of the 465 URS cases with 42.9% of these Clavien II or more. The representation rate to our Emergency Departments was 15.4%. Only 49.1% (201) of patients had a follow-up review with imaging to assess stone free rates. Of the 201 patients who underwent imaging, only 38.3% were stone free. Stone analysis was performed in 34.5%. CONCLUSION: Less than half of all patients were reviewed despite undergoing expensive, time consuming surgery for a condition with a high recurrence rate. In agreement with recent publications stone-free rates were low, with significant complications and representation rates. Stone surgery should be given the attention and resources equivalent to cancer surgery to improve results. LEVEL OF EVIDENCE: 2b.

Production of live offspring following unilateral (left) ovariectomized Potamotrygon rays (Potamotrygon castexi, Potamotrygon leopoldi, and Potamotrygon motoro).

OBJECTIVE: To evaluate the surgical technique and subsequent clinical observations (reproductive and ultrasound findings) of left unilateral ovariectomy in 3 species of Potamotrygon rays-Potamotrygon castexi, Potamotrygon leopoldi, and Potamotrygon motoro-for reproductive management. ANIMALS: Between 2018 and 2019, multiple Potamotrygon rays (P castexi, n = 1; P leopoldi, 1; P motoro, 6) underwent left ovariectomies to evaluate this technique for reproductive management. PROCEDURES: At time of surgery, patient age ranged from juvenile to adult. Rays were anesthetized with MS222 buffered with sodium bicarbonate, and a left craniodorsal surgical approach was made to isolate and excise the left ovary. All rays had uneventful recoveries. Eight unilateral ovariectomized females and 6 males were combined in a mixed-species freshwater touch pool of Potamotrygon rays and teleost species. RESULTS: In December 2020, 3 live and 1 premature autolyzed pup were noted in the habitat. The following day, the adult females were examined via ultrasound and separated from the males. Four dams were identified that produced 8 viable offspring and 4 premature abortions. A large right ovary was observed in all females, with no evidence of left ovarian tissue present via ultrasound. CLINICAL RELEVANCE: Previous histologic evaluation of freshwater ray ovarian tissue suggests both ovaries may be functionally active yet maintain left dominance like some other elasmobranch species. This manuscript provides proof the right ovary alone can produce live offspring. Furthermore, the enlarged right ovary observed in these females suggests that removal of the left ovary may result in compensatory enlargement of the right ovary.

Engineering active lysostaphin variants that incorporate noncanonical amino acids and characterizing the effects of site-specific PEGylation.

We describe a facile strategy to identify sites for the incorporation of noncanonical amino acids into lysostaphin-an enzyme that degrades the cell wall of Staphylococcus aureus-while retaining stapholytic activity. We used this strategy to generate active variants of lysostaphin incorporating para-azidophenylalanine. The incorporation of this "reactive handle" enabled the orthogonal site-specific modification of the enzyme variants with polyethylene glycol (PEG) using copper-free click cycloaddition. PEGylated lysostaphin variants could retain their stapholytic activity, with the extent of retention depending on the site of modification and the PEG molecular weight. The site-specific modification of lysostaphin could be useful not only for PEGylation to improve biocompatibility but also for the incorporation of the enzyme into hydrogels and other biomaterials and for studies of protein structure and dynamics. Moreover, the approach described herein could be readily applied to identify suitable sites for the incorporation of reactive handles into other proteins of interest.

Development of an Amplicon Nanopore Sequencing Strategy for Detection of Mutations Conferring Intermediate Resistance to Vancomycin in Staphylococcus aureus Strains.

Staphylococcus aureus is a major cause of bacteremia and other hospital-acquired infections. The cell-wall active antibiotic vancomycin is commonly used to treat both methicillin-resistant (MRSA) and sensitive (MSSA) infections. Vancomycin intermediate S. aureus (VISA) variants can arise through de novo mutations. Here, we performed pilot experiments to develop a combined PCR/long-read sequencing-based method for detection of previously known VISA-causing mutations. Primers were designed to generate 10 amplicons covering 16 genes associated with the VISA phenotype. We sequenced amplicon pools as long reads with Oxford Nanopore adapter ligation on Flongle flow cells. We then detected mutations by mapping reads against a parental consensus or known reference sequence and comparing called variants against a database of known VISA mutations from laboratory selection. Each amplicon in the pool was sequenced to high (>1,000×) coverage, and no relationship was found between amplicon length and coverage. We also were able to detect the causative mutation (walK 646C>G) in a VISA mutant derived from the USA300 strain (N384-3 from parental strain N384). Mixing mutant (N384-3) and parental (N384) DNA at various ratios from 0 to 1 mutant suggested a mutation detection threshold of the average minor allele frequency (6.5%) at 95% confidence (two standard errors above mean mutation frequency). The study lays the groundwork for direct S. aureus antibiotic resistance genotype inference using rapid nanopore sequencing from clinical samples. IMPORTANCE Bacteremia mortality is known to increase rapidly with time after infection, making rapid diagnostics and treatment necessary. Successful treatment depends on correct administration of antibiotics based on knowledge of strain antibiotic susceptibility. Staphylococcus aureus is a major causative agent of bacteremia that is also commonly antibiotic resistant. In this work, we develop a method to accelerate detection of a complex, polygenic antibiotic resistance phenotype in S. aureus, vancomycin-intermediate resistance (VISA), through long-read genomic sequencing of amplicons representing genes most commonly mutated in VISA selection. This method both rapidly identifies VISA genotypes and incorporates the most comprehensive database of VISA genetic determinants known to date.

Cervical Cancer Screening and Follow-Up Practices in U.S. Prisons.

INTRODUCTION: The objective of this study is to better understand cervical cancer screening and follow-up practices in U.S. prisons. METHODS: A 29-question survey examining cervical cancer screening practices, education, and facility/patient characteristics was disseminated to state-prison medical directors. RESULTS: A total of 70% (35/50) of state medical directors completed the survey between August 2021 and January 2022. All prison systems provided cervical cancer screening both at intake and specified intervals. A total of 36% provided colposcopy on site, and 9% performed excisional procedures on site. A total of 11 states identified 1‒5 cases of cervical cancer within the last year. Frequently cited challenges included a perceived lack of patient interest, delays in community referral, and lack of follow-up of abnormal results after release. CONCLUSIONS: This study found relatively high rates of screening with a perceived lack of patient interest as the most reported barrier. Follow-up care was also often affected by reported lack of patient interest, delays in community referral for diagnostic procedures, and patient release before follow-up. There is room for further optimization of screening and surveillance among incarcerated women by understanding and addressing systems-based challenges. By understanding patient barriers to primary screening, expanding access to onsite testing and community referral for abnormal results, and streamlining post-release follow-up, disparities in care among incarcerated women can be reduced.

Follicular and Hormonal Changes after Estrous Synchronization in Bottlenose Dolphins.

To gain more knowledge about the influence of hormone regulation on follicle development, ovarian ultrasounds were performed, and urinary hormone profiles were determined in ovulating and non-ovulating female bottlenose dolphins (n = 15) following estrus synchronization with altrenogest. Ovarian ultrasounds were conducted daily, post synchronization to describe follicular recruitment in relationship to the endocrine profile. Follicle sizes were grouped into very small (VSM), small (SM), medium (MD) and large (LG). In ovulating females, two follicular waves were identified, and follicular deviation towards establishing a dominant follicle only occurred during the second wave. For non-ovulating females, only the first wave was observed. For all urinary hormones, the non-ovulating group presented significantly lower concentrations of follicle stimulating hormone (uFSH), luteinizing hormone (uLH), estrone conjugates (uE1-C) and estriol (uE3) but similar progestagen and cortisol concentrations compared to the ovulating group. Concentrations of uE1-C and uE3 and numbers of MD and LG follicles significantly (P < 0.05) increased, while uFSH concentrations significantly (P < 0.05) decreased as ovulation approached. Urinary LH significantly increased concurrently with increasing numbers of LG follicles and decreasing numbers of SM follicles. The characterization of follicular development and its relationship with hormone assessments complements our understanding of follicular recruitment post-synchronization in bottlenose dolphins and provides new information concerning differences between ovulating and non-ovulating females in response to an estrous synchronization protocol.

Regional Variation in Access to Oncologic Care and Racial Disparities Among Cervical Cancer Patients.

OBJECTIVES: The goal of this study was to determine whether access to gynecologic oncologists is correlated with disparate outcomes among cervical cancer patients, especially among Black women. MATERIALS AND METHODS: An ecological study was performed using the National Cancer Database among stage I-IVA cervical cancer patients from 2004 to 2014. Data from the National Cancer Institute, the Society of Gynecologic Oncology, and the United States Census were compiled to describe access to care by region. Factors associated with receipt of optimal treatment (defined as surgery and/or radiation for stage IA-IB1 and IIA1; radiation and chemotherapy for stage IB2, IIA2, IIB-IVA or node positive disease) were identified using multivariate logistic regressions stratified by region, controlling for confounding factors including the number of gynecologic oncologists per states in each subregion. Cox multivariate survival analyses stratified by region were also performed. RESULTS: Of 42,213 women, 17.0% were Black. On multivariate analysis controlling for confounders, all Southern women were less likely to receive optimal treatment (adjusted odds ratio [aOR]: 0.80, 95% confidence interval [95% CI]: 0.75-0.85, P <0.001) compared with Northeastern women. Black women in the South (aOR: 0.76, 95% CI: 0.70-0.83, P <0.001) and Midwest (aOR: 0.78, 95% CI: 0.68-0.90, P <0.001) were less likely to receive optimal treatment compared with non-Black women in those regions. Black women in the South (adjusted hazard ratio [aHR]: 1.11, 95% CI: 1.04-1.18, P <0.001) and West (aHR: 1.34, 95% CI: 1.11-1.62, P =0.002) had worse mortality compared with non-Black women in those regions, despite controlling for access to gynecologic oncologists. The South, Midwest, and West had proportionally fewer cancer centers and gynecologic oncologists compared with the Northeast. CONCLUSIONS: Southern women are at risk of inadequate treatment for cervical cancer, and Black Southern women are at even higher risk of inadequate treatment and worse overall survival despite controlling for access to gynecologic oncologists. Social determinants of health and other barriers besides access to oncologists likely contribute to observed regional and racial disparities among cervical cancer patients.

The impact of fibrodysplasia ossificans progressiva (FOP) on patients and their family members: results from an international burden of illness survey.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, genetic disorder of heterotopic ossification within soft, connective tissues resulting in limited joint function and severe disability. We present results from an international burden of illness survey (NCT04665323) assessing physical, quality of life (QoL), and economic impacts of FOP on patients and family members. METHODS: Patient associations in 15 countries invited their members to participate; individuals with FOP and their family members were eligible. The survey was available online, in 11 languages, from 18 January-30 April 2021. Participants responded to assessments measuring joint function, QoL, healthcare service and living adaptation utilization, out-of-pocket costs, employment, and travel. RESULTS: The survey received 463 responses (patients, n = 219; family members, n = 244). For patients, decreased joint function was associated with reduced QoL and greater reliance on living adaptations. Nearly half of primary caregivers experienced a mild to moderate impact on their health/psychological wellbeing. Most primary caregivers and patients (≥18 years) reported that FOP impacted their career decisions. CONCLUSIONS: Data from this survey will improve understanding of the impact of FOP on patients and family members, which is important for identifying unmet needs, optimizing care, and improving support for the FOP community.

"I Can't Take off My Shirt or Do My Own Hair"-A Qualitative Investigation of the Symptoms and Impact Experience of Children and Adolescents with Fibrodysplasia Ossificans Progressiva (FOP).

INTRODUCTION: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling, autosomal dominant, congenital disease characterized by progressive multi-focal heterotopic ossification (HO) of skeletal muscle, ligaments, tendons, and fascia. Past FOP studies have focused on the clinical aspects of the disease; therefore, there is a paucity of qualitative research on the patient experience. Our objective was to better understand the experience of children and adolescents living with FOP from their and their parents' perspectives. METHODS: We conducted a qualitative research study comprising in-depth, open-ended interviews with children and adolescents with FOP and their parents. Semi-structured interviews were conducted via phone call or Microsoft Teams with parent-child dyads (n = 11), adolescents (n = 6), and two clinicians. Children/adolescents and their parents were asked open-ended questions to elicit their daily experience of FOP. RESULTS: Concepts were organized into two major themes: symptoms of FOP and the impact of FOP on daily life. Symptoms of FOP reported by children/adolescents, parents, and clinicians were pain, swelling, redness, and stiffness. Functional impacts of flares and FOP in general included accommodations, mobility, activities of daily living, daily activities, and social activities. Impacts were attributed to the difficulties children and adolescents faced living with a disease that prohibited common activities. CONCLUSIONS: This research documented the experience of children and adolescents with FOP and its effects on their daily lives. It provides a conceptual model for further exploration of the symptoms and impacts important to children and adolescents with FOP and their parents. Children and adolescents and their parents offered novel insights into life with the disease that have not previously been discussed in published literature. Future studies should build upon our conceptual model to create a holistic view of the patient experience of FOP, to inform clinical practice, and the assessment of the patient experience in clinical trials for the disease.

Current challenges and opportunities in the care of patients with fibrodysplasia ossificans progressiva (FOP): an international, multi-stakeholder perspective.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, disabling genetic disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification of soft and connective tissues. Assiduous attention to the unmet needs of this patient community is crucial to prevent potential iatrogenic harm and optimize care for individuals with FOP. OBJECTIVE: To gather international expert opinion and real-world experience on the key challenges for individuals with FOP and their families, highlight critical gaps in care, communication, and research, and provide recommendations for improvement. METHODS: An international group of expert clinicians, patients and patient advocates, caregivers and representatives from the international FOP community participated in a virtual, half-day meeting on 22 March 2021 to discuss the key unmet needs of individuals with FOP. RESULTS: Individuals with FOP often face the frustration of long diagnostic journeys, the burden of self-advocacy and the navigation of novel care pathways. Globally, patients with FOP are also confronted with inequities in access to diagnosis and specialist care, and consequently, unequal access to registries, clinical trials, and essential support from patient associations. Organizations such as the International FOP Association, the International Clinical Council on FOP, and national FOP organizations work to provide information, facilitate access to expert clinical guidance, nurture patient empowerment, fund FOP research and/or foster meaningful collaborations with the research community. The non-profit Tin Soldiers Global FOP Patient Search program aims to identify and provide a pathway to diagnosis and care for individuals with FOP, particularly in underserved communities. Such global initiatives and the increasingly widespread use of telemedicine and digital platforms offer opportunities to improve vital access to care and research. CONCLUSIONS: This multi-stakeholder perspective highlights some of the unmet needs of individuals with FOP and their families. Regional and international organizations play an important role in improving the quality of life of those they reach in the global FOP community. However, globally, fundamental issues remain around raising awareness of FOP among healthcare professionals, identifying individuals with FOP, reducing time to diagnosis, and ensuring access to best practice in care, support, and clinical research. Medical writing support was industry-sponsored.

Efficacy of VERIGENE® Blood Culture Assays in Accurately and Rapidly Detecting Gram-Negative and Gram-Positive Pathogens.

BACKGROUND: Rapid administration of appropriately indicated antibiotics is crucial in septic patients. Sepsis data supports that there is a higher risk of mortality for each hour delay from triage to antibiotic therapy, as well as for inappropriate antibiotic selection. There are a variety of rapid microbial detection systems, such as VERIGENE®, used in acute care facilities to rapidly detect bacteremia and identify resistance markers. Our study investigates the usefulness of VERIGENE® assays in accurately detecting Gram-positive and Gram-negative pathogens when compared to traditional blood culture analysis systems, such as VITEK®. METHODS: 819 Gram-positive and 373 Gram-negative blood samples were collected and tested using both VERIGENE® and VITEK®. Statistical tests were two-tailed and observations were defined as statistically significant if P ≤ 0.05. RESULTS: VERIGENE® detected a pathogen in 816/819 (99.6%) samples of the Gram-positive blood cultures and 367/373 (98.3%) samples of the Gram-negatives compared to 805/819 (98.3%) and 367/373 (98.4%), respectively, using VITEK®. Gram-positive cultures had a sensitivity of 99.5% and a specificity of 27.3% (PPV 99.0%, NPV 42.9%, 98.7% accuracy) with VERIGENE analysis. Gramnegatives had a sensitivity of 99.2% and a specificity of 20.0% (PPV 98.9%, NPV 25.0%, 98.4% accuracy). CONCLUSION: Although statistically insignificant (P = 0.25), VERIGENE® was 1.3% more likely to identify Gram-positive bacteria when compared to conventional methods. Overall, we concluded that VERIGENE® assays are valuable in their ability to rapidly detect microorganisms and resistance markers, given their high sensitivities. This allows for select targeted therapy in patients with sepsis and can ultimately reduce mortality rates.

Prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa and association with clinical outcomes in patients: an observational study.

OBJECTIVES: To describe the prevalence of colistin heteroresistance in carbapenem-resistant Pseudomonas aeruginosa (CRPA) and evaluate the association with clinical outcomes. METHODS: Colistin heteroresistance was evaluated in CRPA isolates collected from patients without cystic fibrosis in Atlanta, Georgia, USA using two definitions: HR1, growth at 4 and 8 mg/L of colistin at a frequency ≥1 × 10-6 the main population; and HR2, growth at a colistin concentration ≥8× the MIC of the main population at a frequency ≥1 × 10-7. A modified population analysis profile (mPAP) technique was compared with reference PAP for detecting heteroresistance. For adults hospitalized at the time of or within 1 week of CRPA culture, multivariable logistic regression estimated the association between heteroresistance and 90 day mortality. RESULTS: Of 143 colistin-susceptible CRPA isolates, 8 (6%) met the HR1 definition and 37 (26%) met the HR2 definition. Compared with the reference PAP, mPAP had a sensitivity and specificity of 50% and 100% for HR1 and 32% and 99% for HR2. Of 82 hospitalized patients, 45 (56%) were male and the median age was 63 years (IQR 49-73). Heteroresistance was not associated with 90 day mortality using HR1 (0% in heteroresistant versus 22% in non-heteroresistant group; P = 0.6) or HR2 (12% in heteroresistant versus 24% in non-heteroresistant group; P = 0.4; adjusted OR 0.8; 95% CI 0.2-3.4). CONCLUSIONS: Colistin heteroresistance was identified in up to 26% of patients with CRPA in our sample, although the prevalence varied depending on the definition. We did not observe an apparent association between colistin heteroresistance and 90 day mortality.

EFFICACY OF HUMAN RECOMBINANT GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF, FILGRASTIM; NEUPOGEN®) IN NEUTROPENIC CETACEANS.

Neutrophils are one of the initial cell lines of protection against pathogens, and when their concentrations in the blood are low, animals are highly susceptible to infections. Neutropenia has been reported in cetaceans secondary to administration of systemic sulfa antibiotics or antifungal medications and severe, overwhelming infection. Filgrastim was administered to treat neutropenia over a 15-y period in 11 cetaceans comprising four species-beluga (Delphinapterus leucas, n = 1), bottlenose dolphin (Tursiops truncatus, n = 4), killer whale (Orcinus orca, n = 5), and short-finned pilot whale (Globicephala macrorhynchus, n = 1)] ranging in age from 1 wk to >24 y. Seven study animals received multiple doses (2-6). All animals responded to at least one dose (1-7 µg/kg) of parenteral filgrastim characterized by an increase in peripheral immature (band) neutrophils, segmented neutrophils, or both. In most cases (9/11), neutrophil counts increased within 48 h of a single dose. Duration of response varied but was at least 2 wk in eight of the 11 animals and 5-9 d in the remaining animals. No adverse reactions were observed in any cases.

Impact of clinical characteristics on human chorionic gonadotropin regression after molar pregnancy.

OBJECTIVES: This study aimed to determine the effects of age, race/ethnicity, body mass index, and contraception on human chorionic gonadotropin (hCG) regression following the evacuation of a molar pregnancy. METHODS: This was a retrospective cohort study of 277 patients with molar pregnancies between January 1, 1994 and December 31, 2015. The rate of hCG regression was estimated using mixed-effects linear regression models on daily log-transformed serum hCG levels after evacuation. RESULTS: There were no differences in hCG half-lives among age (p=0.13) or race/ethnicity (p=0.16) groups. Women with obesity and hormonal contraceptive use demonstrated faster hCG regression than their counterparts (3.2 versus. 3.7 days, p=0.02 and 3.4 versus. 4.0 days, p=0.002, respectively). CONCLUSION: Age and race/ethnicity were not associated with hCG regression rates. Hormonal contraceptive use and obesity were associated with shorter hCG half-lives, but with unlikely clinical significance. It is important to understand whether the clinical characteristics of patients may influence the hCG regression curve, as it has been proposed as a way to predict the risk of gestational trophoblastic neoplasia.

Effect of genetic background on the evolution of Vancomycin-Intermediate Staphylococcus aureus (VISA).

Vancomycin-intermediate Staphylococcus aureus (VISA) typically arises through accumulation of chromosomal mutations that alter cell-wall thickness and global regulatory pathways. Genome-based prediction of VISA requires understanding whether strain background influences patterns of mutation that lead to resistance. We used an iterative method to experimentally evolve three important methicillin-resistant S. aureus (MRSA) strain backgrounds-(CC1, CC5 and CC8 (USA300)) to generate a library of 120 laboratory selected VISA isolates. At the endpoint, isolates had vancomycin MICs ranging from 4 to 10 µg/mL. We detected mutations in more than 150 genes, but only six genes (already known to be associated with VISA from prior studies) were mutated in all three background strains (walK, prs, rpoB, rpoC, vraS, yvqF). We found evidence of interactions between loci (e.g., vraS and yvqF mutants were significantly negatively correlated) and rpoB, rpoC, vraS and yvqF were more frequently mutated in one of the backgrounds. Increasing vancomycin resistance was correlated with lower maximal growth rates (a proxy for fitness) regardless of background. However, CC5 VISA isolates had higher MICs with fewer rounds of selection and had lower fitness costs than the CC8 VISA isolates. Using multivariable regression, we found that genes differed in their contribution to overall MIC depending on the background. Overall, these results demonstrated that VISA evolved through mutations in a similar set of loci in all backgrounds, but the effect of mutation in common genes differed with regard to fitness and contribution to resistance in different strains.