Machine learning in time-lapse imaging to differentiate embryos from young vs old mice†.

Time-lapse microscopy for embryos is a non-invasive technology used to characterize early embryo development. This study employs time-lapse microscopy and machine learning to elucidate changes in embryonic growth kinetics with maternal aging. We analyzed morphokinetic parameters of embryos from young and aged C57BL6/NJ mice via continuous imaging. Our findings show that aged embryos accelerated through cleavage stages (from 5-cells) to morula compared to younger counterparts, with no significant differences observed in later stages of blastulation. Unsupervised machine learning identified two distinct clusters comprising of embryos from aged or young donors. Moreover, in supervised learning, the extreme gradient boosting algorithm successfully predicted the age-related phenotype with 0.78 accuracy, 0.81 precision, and 0.83 recall following hyperparameter tuning. These results highlight two main scientific insights: maternal aging affects embryonic development pace, and artificial intelligence can differentiate between embryos from aged and young maternal mice by a non-invasive approach. Thus, machine learning can be used to identify morphokinetics phenotypes for further studies. This study has potential for future applications in selecting human embryos for embryo transfer, without or in complement with preimplantation genetic testing.

Determining a urinary-specific antibiogram and risk factors of trimethoprim/sulfamethoxazole, ciprofloxacin and multidrug resistance among Enterobacterales in primary care.

BACKGROUND: Risk factors for ciprofloxacin or MDR in primary care urine specimens are not well defined. OBJECTIVES: We created a primary care-specific antibiogram for Escherichia coli isolates from cases with complicated and uncomplicated urinary tract infection (UTI) and evaluated risk factors for ciprofloxacin, trimethoprim/sulfamethoxazole and MDR among Enterobacterales. METHODS: We conducted a cross-sectional study to determine resistance and risk factors by collecting urine cultures from all patients (≥18 years) presenting with provider-suspected UTI at two primary care, safety-net clinics in Houston, TX, USA between November 2018 and March 2020. RESULTS: Among 1262 cultures, 308 cultures grew 339 uropathogens. Patients with Enterobacterales (n = 199) were mostly female (93.5%) with a mean age of 48.5 years. E. coli was the predominant uropathogen isolated (n = 187/339; 55%) and had elevated trimethoprim/sulfamethoxazole (43.6%) and ciprofloxacin (29.5%) resistance, low nitrofurantoin (1.8%) resistance, and no fosfomycin resistance. Among E. coli, 10.6% were ESBL positive and 24.9% had MDR. Birth outside the U.S.A., prior (2 year) trimethoprim/sulfamethoxazole resistance, and diabetes mellitus were associated with trimethoprim/sulfamethoxazole resistance. Prior (60 day) fluoroquinolone use, prior ciprofloxacin resistance and both diabetes mellitus and hypertension were strongly associated with ciprofloxacin resistance. Prior fluoroquinolone use and a history of resistance to any studied antibiotic were associated with MDR, while pregnancy was protective. CONCLUSIONS: We found elevated resistance to UTI-relevant antimicrobials and novel factors associated with resistance; these data can be incorporated into clinical decision tools to improve organism and drug concordance.

Using Trauma Video Review to Assess EMS Handoff and Trauma Team Non-Technical Skills.

OBJECTIVE: Handoffs by emergency medical services (EMS) personnel suffer from poor structure, inattention, and interruptions. The relationship between the quality of EMS communication and the non-technical performance of trauma teams remains unknown. METHODS: We analyzed 3 months of trauma resuscitation videos (highest acuity activations or patients with an Injury Severity Score [ISS] of ≥15). Handoffs were scored using the mechanism-injury-signs-treatment (MIST) framework for completeness (0-20), efficiency (category jumps), interruptions, and timeliness. Trauma team non-technical performance was scored using the Trauma Non-Technical Skills (T-NOTECHS) scale (5-15). RESULTS: We analyzed 99 videos. Handoffs lasted a median of 62 seconds [IQR: 43-74], scored 11 [10-13] for completeness, and had 2 [1-3] interruptions. Most interruptions were verbal (85.2%) and caused by the trauma team (64.9%). Most handoffs (92%) were efficient with 2 or fewer jumps. Patient transfer during handoff occurred in 53.5% of the videos; EMS providers giving handoff helped transfer in 69.8% of the Primary surveys began during handoff in 42.4% of the videos. Resuscitation teams who scored in the top-quartile on the T-NOTECHS (>11) had higher MIST scores than teams in lower quartiles (13 [11.25-14.75] vs. 11 [10-13]; p < .01). There were no significant differences in ISS, efficiency, timeliness, or interruptions between top- and lower-quartile groups. CONCLUSIONS: There is a relationship between EMS MIST completeness and high performance of non-technical skill by trauma teams. Trauma video review (TVR) can help identify modifiable behaviors to improve EMS handoff and resuscitation efforts and therefore trauma team performance.

Association between biventricular pacing and incidence of ventricular arrhythmias in the early post-operative period after left ventricular assist device implantation.

INTRODUCTION: Cardiac resynchronization therapy (CRT) and left ventricular assist devices (LVAD) improve outcomes in heart failure patients. Early ventricular arrhythmias (VA) are common after LVAD and are associated with increased mortality. The association between left ventricular pacing (LVP) with CRT and VAs in the early post-LVAD period remains unclear. METHODS: This was a retrospective study of all patients undergoing LVAD implantation from 1/2016 to 12/2019. Patients were divided into those with CRT and active LVP (CRT-LVP) immediately post-LVAD implant versus those without CRT-LVP. Implantable cardiac defibrillator electrograms were reviewed and early VAs were defined as sustained ventricular tachycardia (VT)/ventricular fibrillation occurring within 30 days of LVAD implantation. RESULTS: Of 186 included patients (mean age 53 years, 75% male, mean body mass index 28), 72 had CRT devices, 63 of whom had LV pacing enabled after LVAD implant (CRT-LVP group). Patients with CRT-LVP were more likely to have VA in the early postoperative period (21% vs. 4%; p = .0001). All 9 patients with CRT in whom LVP was disabled had no early VA. Among those with early VA, patients with CRT-LVP were more likely to have monomorphic VT (77% vs. 40%; p = .07). In multiple logistic regression, CRT-LVP pacing remained an independent predictor of early VA after adjustment for history of VA and AF. CONCLUSIONS: Patients with CRT-LVP after LVAD implant had a higher incidence of early VA (specifically monomorphic VT). Epicardial LV pacing may be proarrhythmic in the early postoperative period after LVAD.

Molecular Testing for Acute Respiratory Tract Infections: Clinical and Diagnostic Recommendations From the IDSA's Diagnostics Committee.

The clinical signs and symptoms of acute respiratory tract infections (RTIs) are not pathogen specific. Highly sensitive and specific nucleic acid amplification tests have become the diagnostic reference standard for viruses, and translation of bacterial assays from basic research to routine clinical practice represents an exciting advance in respiratory medicine. Most recently, molecular diagnostics have played an essential role in the global health response to the novel coronavirus pandemic. How best to use newer molecular tests for RTI in combination with clinical judgment and traditional methods can be bewildering given the plethora of available assays and rapidly evolving technologies. Here, we summarize the current state of the art with respect to the diagnosis of viral and bacterial RTIs, provide a practical framework for diagnostic decision making using selected patient-centered vignettes, and make recommendations for future studies to advance the field.

Using the Medial and Lateral Humeral Lines as an Adjunct to Intraoperative Elbow Arthrography to Guide Intraoperative Reduction and Fixation of Distal Humerus Physeal Separations Reduces the Incidence of Postoperative Cubitus Varus.

BACKGROUND: Distal humerus physeal separations are rare pediatric elbow fractures that are often misdiagnosed and difficult to treat. Adequate reduction is often technically challenging and up to 71% of children develop postoperative cubitus varus. We propose using the medial and lateral humeral lines as an adjunct to elbow arthrography in order to guide intraoperative fixation of distal humerus physeal separations to reduce the incidence of postoperative cubitus varus. METHODS: From 2009 to 2014, all pediatric patients under the age of 3 diagnosed with a distal humerus physeal separation and treated surgically at our institution were included for analysis. Two senior pediatric orthopaedic surgeons separately reviewed the preoperative, intraoperative, and postoperative images of all patients and measured the position of the ulnar axis relative to the medial and lateral humeral lines. The medial and lateral humeral shafts were defined as parallel lines drawn along the medial and lateral humeral diaphysis. Adequate reduction was defined by reduction of the ulnar axis within the boundaries of the medial and lateral humeral lines. Patients were assessed at latest follow-up for cubitus varus and any other surgical complications. RESULTS: Thirteen patients fulfilled the inclusion criteria and were on average 1.70 years old, ranging from 0.62 to 3 years old. Intraoperatively and immediately postoperatively, all 13 patients (100%) were noted to have adequate reduction of the ulnar axis within the boundaries medial and lateral humeral lines. None of the patients required intraoperative arthrography (0%). At the date of latest follow-up, 12 patients (92.3%) had no angular deformities compared with the contralateral limb and 1 patient (7.7%) had developed cubitus varus. No surgical complications were noted (0%). CONCLUSION: Intraoperative reduction of the ulnar axis within the boundaries of the medial and lateral humeral lines is associated with a lower incidence of postoperative cubitus varus in the treatment of distal humerus physeal separations in children. LEVEL OF EVIDENCE: Level IV.

The Use of C-reactive Protein as a Guide for Transitioning to Oral Antibiotics in Pediatric Osteoarticular Infections.

BACKGROUND: In the treatment of pediatric osteoarticular infections, early transition to oral antibiotics is desirable to shorten hospital stays and complications of prolonged intravenous therapy. C-reactive protein (CRP) is an acute phase reactant with a short half-life and is utilized at our institution to monitor progress and determine the transition to oral antibiotics. We hypothesized that patients can be safely transitioned from parenteral antibiotics to oral antibiotics when patients improve clinically and CRP halves over a period of 4 days. MATERIALS AND METHODS: A retrospective review was conducted of all pediatric patients between the ages of 1 month and 18 years admitted and treated for acute bacterial osteomyelitis and/or septic arthritis at the authors' institution. We recorded all relevant data, inpatient progress, and outpatient follow-up. RESULTS: Thirty-seven patients fulfilled the selection criteria and were reviewed for this study. Patients were an average of 8.37±4.91 years old. Surgery was performed in 33 patients (89.2%). The average duration of intravenous antibiotics was 11.00±5.61 days and the average duration of oral antibiotics was 28.76±8.69 days, with an average total duration of antibiotics of 39.16±9.08 days. The average peak CRP was 156.91±97.81 mg/L and the average CRP at discharge was 24.94±22.36 mg/L. Thirty-four patients (91.89%) experienced a 50% decline in CRP over 4 days. Of these patients, only 1 (2.94%) went on develop complications in the follow-up period. The average hospitalization period was 11.50±6.55 days. The average duration of follow-up was 7.83±6.56 months. CONCLUSIONS: We found that the combination of clinical improvement and a specific reduction of 50% in CRP levels over 4 days, or 5 CRP half lives, could be used to determine when to transition children with osteoarticular infections from parenteral to oral therapy. Complicated outcomes were associated with negative cultures, longer hospitalizations, and persistently elevated CRP levels.

Endoscopic Plantar Fasciotomy Improves Early Postoperative Results: A Retrospective Comparison of Outcomes After Endoscopic Versus Open Plantar Fasciotomy.

Plantar fasciotomy is offered to patients with recalcitrant plantar fasciitis. Few studies have characterized the functional outcomes over time for the endoscopic approach compared with the open approach. We hypothesized that patients undergoing endoscopic surgery will have better postoperative functional outcomes early in the postoperative period but equivalent long-term outcomes compared with patients undergoing open surgery. We analyzed the prospectively collected data of all patients undergoing plantar fasciotomy at our institution from December 2007 to August 2014. A total of 42 feet of 38 patients were included in the analysis. The clinical data were collected preoperatively and at 3 and 6 months and 1 year. The functional outcomes analyzed included the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale, the Medical Outcomes Study, Short-Form, 36-item Health Survey, and patient satisfaction and expectations. Patients undergoing endoscopic surgery had significantly greater American Orthopaedic Foot and Ankle Society Ankle-Hindfoot and SF-36 Health Survey scores and lower pain scores at the 3-month period. They were also significantly more likely to be satisfied with and have had their expectations met by surgery. Compared with the open approach, the patients who had undergone endoscopic plantar fasciotomy experienced significantly greater improvements in the subjective and objective functional outcomes, with less pain and greater satisfaction, and had had their expectations met earlier in the recovery period, with equivalent long-term outcomes, compared with the patients who had undergone open plantar fasciotomy.

Radiofrequency microtenotomy is as effective as plantar fasciotomy in the treatment of recalcitrant plantar fasciitis.

BACKGROUND: Radiofrequency microtenotomy (RM) is effective for treating plantar fasciitis. No studies have compared it to the plantar fasciotomy (PF). We hypothesized that RM is equally effective and provides no additional benefit when performed with PF. METHODS: Between 2007 and 2014, all patients who underwent either or both procedures concurrently at our institution were analyzed. Data collected included demographics, SF-36 Health Survey, AOFAS Ankle-Hindfoot Scale, and two questions regarding satisfaction and expectations, all of which were assessed pre-operatively and post-operatively at 6-months and 1-year. ANOVA with Bonferroni correction was used to compare scores at each interval. Logistic regression was used to identify pre-operative factors that predicted for satisfaction and expectations. RESULTS: There were no differences in patient outcomes. No pre-operative factors predicted for satisfaction and expectations. CONCLUSIONS: RM is as effective as PF in the treatment of plantar fasciitis. Patients who underwent both procedures experienced no benefit and a higher rate of complications.

Eosinophilia in patients infected with human immunodeficiency virus.

Eosinophilia is not uncommonly encountered in patients infected with human immunodeficiency virus (HIV), particularly at initiation of care or among those with advanced disease. The clinical manifestation most commonly associated with eosinophilia in this patient population is skin rash. Management of these patients is challenging due to a paucity of data evaluating diagnostic testing and therapeutic strategies. Patients born in or with significant travel to parasite-endemic countries are more likely to have tissue-invasive helminthes, such as Strongyloides or Schistosoma. Patients without such risk factors are unlikely to have parasitic infections and frequently will have self-resolution of eosinophilia. When a detailed history, physical exam, and diagnostic work-up are unrevealing, we sometimes consider empirical therapy with ivermectin. Praziquantel may also be considered for those at risk for schistosomiasis.

Are patients more satisfied and have better functional outcome after bilateral total knee arthroplasty as compared to total hip arthroplasty and unilateral total knee arthroplasty surgery? A two-year follow-up study.

This study aims to review the quality of life and physical improvement achieved by total joint arthroplasty surgery, namely unilateral TKA, bilateral TKA and THA. We hypothesize that patients who undergo bilateral TKA should have greater improvement in patient-reported outcome measures, as compared to patients who had unilateral TKA, and their outcomes may be comparable to that of THA. We analyzed prospectively collected data of all patients who underwent unilateral TKA, bilateral TKA and THA (5291, 187 and 529 patients respectively) for end-stage osteoarthritis at a tertiary hospital during the 5-year period. Patients who underwent bilateral TKA had a greater degree of improvement in SF-36 and Knee Society Scores as compared to unilateral TKA at 6 months and 2 years follow-up. Bilateral TKA had the highest proportion of patients who were satisfied and had expectations met by surgery.

Comparison of patient quality of life scores and satisfaction after common orthopedic surgical interventions.

Patient quality of life scores are commonly used to assess patient-reported satisfaction following orthopedic interventions. Our main aim was to review the satisfaction scores of four common orthopedic interventions in our tertiary institution, primary hallux valgus (HV) corrective surgery, primary single-level transforaminal lumbar interbody fusion (TLIF), primary unilateral total knee arthroplasty (TKA) and primary total hip arthroplasty (THA). We retrospectively reviewed prospectively collected data on patients who underwent four different types of orthopedic surgeries using the SF-36 score and two questions adopted from North American Spine Society Questionnaire. The database of a tertiary hospital between January 2007 and December 2009 was reviewed. There were 3488, 374, 184 and 73 patients who underwent TKA, THA, TLIF and HV surgery, respectively. Patients who underwent primary TLIF, TKA and THA had significant degree of improvement in all aspects of SF-36 scores at 6 months and 2 years of follow-up (p < 0.001). Postoperatively at 2 years, the most satisfied postoperative patients were those who underwent THA (91.9 %), followed by TKA (90.5 %), TLIF (86.1 %) and HV (77.4 %). This study shows a significant degree of postoperative improvement in terms of SF-36 scores for common orthopedic interventions in particular to primary TKA, THA and TLIF at 6 months and 2 years of follow-up. With a significant degree of improvement in SF-36 scores postoperatively, this also translated into patient satisfaction and meeting their expectations of surgery.

Posterior left atrial isolation is associated with a lower incidence of atrial tachycardia in patients with persistent atrial fibrillation.

BACKGROUND: Patients may develop atrial tachycardia (AT) after left atrial (LA) ablation of persistent atrial fibrillation (AF). METHODS: The population consisted of 101 consecutive patients (age = 64.3 ± 8.7 years, 70 males (69%), LA = 4.6 ± 0.8 cm, ejection fraction = 48.5 ± 16%) undergoing their initial procedure for persistent AF. After pulmonary vein isolation, patients either underwent posterior LA isolation (n = 50; study group) or linear ablation at the LA roof with verification of conduction block (n = 51; control group). RESULTS: A repeat procedure was performed in 17 (34%) and 28 (55%) patients in the study and control groups, respectively (p = 0.02). Patients in the study group were less likely to develop AT (9/50 [18%] vs. 18/51 [35%]; p = 0.02), roof-dependent (1/50 [2%] vs. 8/51 [16%]; p = 0.008), and multi-loop AT (6/50 [12%] vs. 14/51 [27%]; p = 0.03) as compared to controls. Among various factors, only posterior LA isolation was associated with a lower likelihood of AT recurrence and roof tachycardia at redo procedure (OR, 0.37; 95% CI, 0.1 to 1.00, p = 0.05, and OR, 0.1, 95% CI, 0.01 to 0.96; p < 0.05, respectively). CONCLUSIONS: In patients with persistent AF, posterior LA isolation is associated with a lower risk of a redo procedure, roof-dependent macro-reentry, and post-ablation AT in general as compared to controls who only received roof ablation. Posterior LA isolation also obviates the need for pacing maneuvers, and may be a more definitive endpoint than linear ablation at the LA roof.

Real-world experience with cefiderocol therapy for Pseudomonas aeruginosa and other multidrug resistant gram-negative infections within the Veterans Health Administration, 2019-2022.

Objective: Single-center and regional studies have reported outcomes after treatment with cefiderocol, a novel siderophore cephalosporin. We report on real-world use, clinical outcomes, and microbiological outcomes with cefiderocol therapy within the Veterans' Health Administration (VHA). Design: Prospective, observational descriptive study. Setting: Veterans' Health Administration, 132 sites across the United States, during 2019-2022. Patients: This study included patients admitted to any VHA medical center who received cefiderocol for ≥2 days. Methods: Data were obtained from the VHA Corporate Data Warehouse and through manual chart review. We extracted clinical and microbiologic characteristics and outcomes. Results: In total, 8,763,652 patients received 1,142,940,842 prescriptions during the study period. Of these, 48 unique individuals received cefiderocol. The median age of this cohort was 70.5 years (IQR, 60.5-74), and the median Charlson comorbidity score was 6 (IQR, 3-9). The most common infectious syndromes were lower respiratory tract infection in 23 patients (47.9%) and urinary tract infection in 14 patients (29.2%). The most common pathogen cultured was P. aeruginosa in 30 patients (62.5%). The clinical failure rate was 35.4% (17 of 48), and 15 (88.2%) of these 17 patients died within 3 days of clinical failure. The 30-day and 90-day all-cause mortality rates were 27.1% (13 of 48) and 45.8% (22 of 48), respectively. The 30-day and 90-day microbiologic failure rates were 29.2% (14 of 48) and 41.7% (20 of 48), respectively. Conclusions: In this nationwide VHA cohort clinical and microbiologic failure occurred in >30% of patients treated with cefiderocol, and >40% of these died within 90 days. Cefiderocol is not widely used, and many of the patients who received it had substantial comorbidities.

Mortality difference from Klebsiella aerogenes vs Enterobacter cloacae bloodstream infections.

Members of the order Enterobacterales, including Escherichia coli , Klebsiella species and Enterobacter species, are important pathogens in healthcare-associated infections. Higher mortality has been reported from infections due to Klebsiella pneumoniae than from E. coli , but prior studies comparing Enterobacter aerogenes (recently renamed Klebsiella aerogenes ) bacteraemia and Enterobacter cloacae complex bacteraemia have yielded conflicting results regarding whether clinical outcomes differ. We found bacteraemia with K. aerogenes was independently associated with greater risk of 30-day mortality than bacteraemia with Enterobacter cloacae complex.

Inflammatory Biomarkers Differ among Hospitalized Veterans Infected with Alpha, Delta, and Omicron SARS-CoV-2 Variants.

Mortality due to COVID-19 has been correlated with laboratory markers of inflammation, such as C-reactive protein (CRP). The lower mortality during Omicron variant infections could be explained by variant-specific immune responses or host factors, such as vaccination status. We hypothesized that infections due to Omicron variant cause less inflammation compared to Alpha and Delta, correlating with lower mortality. This was a retrospective cohort study of veterans hospitalized for COVID-19 at the Veterans Health Administration. We compared inflammatory markers among patients hospitalized during Omicron infection with those of Alpha and Delta. We reported the adjusted odds ratio (aOR) of the first laboratory results during hospitalization and in-hospital mortality, stratified by vaccination status. Of 2,075,564 Veterans tested for COVID-19, 29,075 Veterans met the criteria: Alpha (45.1%), Delta (23.9%), Omicron (31.0%). Odds of abnormal CRP in Delta (aOR = 1.85, 95% CI:1.64-2.09) and Alpha (aOR = 1.94, 95% CI:1.75-2.15) were significantly higher compared to Omicron. The same trend was observed for Ferritin, Alanine aminotransferase, Aspartate aminotransferase, Lactate dehydrogenase, and Albumin. The mortality in Delta (aOR = 1.92, 95% CI:1.73-2.12) and Alpha (aOR = 1.68, 95% CI:1.47-1.91) were higher than Omicron. The results remained significant after stratifying the outcomes based on vaccination status. Veterans infected with Omicron showed milder inflammatory responses and lower mortality than other variants.

Quantifying the Implementation and Cost of a Multisite Antibiotic Stewardship Intervention for Asymptomatic Bacteriuria.

Objective: The intensity of an antibiotic stewardship intervention to achieve clinical impact is not known. We conducted a multisite dissemination project of an intervention to reduce treatment of asymptomatic bacteriuria (ASB) and studied: (1) the association between implementation metrics and clinical outcomes and (2) the cost of implementation. Design/Setting/Participants: A central site facilitated a multimodality intervention to decrease unnecessary urine cultures and antibiotic treatment in patients with ASB at 4 Veterans Affairs medical centers. Methods: The intervention consisted of a decision support aid algorithm and interactive teaching cases that provided in the moment audit and feedback on how to manage ASB. Implementation outcomes included minutes spent in intervention delivery, number of healthcare professionals reached, and number of sessions delivered. Clinical outcomes included days of antibiotic therapy (DOT), length of antibiotic therapy (LOT), and number of urine cultures ordered per 1000 bed days. Personnel reported weekly time logs. Results: Minutes spent in intervention delivery were inversely correlated with two clinical outcomes, DOT (R -0.3, P = .04) and LOT (R -0.3, P = .02). Number of healthcare professionals reached and number of sessions delivered were not correlated with clinical outcomes of DOT (R -0.003, P = .98, R = -0.059, P = .69) or LOT (R +0.073, P = .62, R -0.102, P = .49). Physician champions spent an average of 3.8% of effort on the intervention. The implementation cost was USD 22,299/year per site on average. Conclusions: The amount of time local teams spent in delivery of an antibiotic stewardship intervention was correlated with the desired decrease in antibiotic use. Implementing this successful antibiotic stewardship intervention required minimal time.