Clinical phenotypes and outcomes associated with SARS-CoV-2 Omicron sublineage JN.1 in critically ill COVID-19 patients: a prospective, multicenter cohort study in France, November 2022 to January 2024.

BACKGROUND: A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients. METHODS: The current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI). RESULTS: During the study period (November 2022-January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21). CONCLUSIONS: Critically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.

COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants.

BACKGROUND: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11-28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. METHODS: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. RESULTS: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4-7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. CONCLUSION: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

Evaluation of the ELITechGroup solution for plasma HIV-1 RNA quantification.

In the last few years, many manufacturers have developed new kits for plasma HIV-1 RNA quantification. Recently, a solution consisting of the ELITe InGenius® instrument and the HIV1 ELITe MGB®kit has been commercialized worldwide. Our aim was to compare its clinical performance with the Aptima® HIV-1 Quant Dx kit by Hologic, on a panel of HIV-1 group M circulating variants, representative of viral load levels found during the pre- and post-treatment follow-up of patients. The linearity was evaluated on the AcroMetrix® HIV-1 Panel. Clinical specificity was evaluated on 100 plasma samples negative for HIV; and clinical sensitivity and sequential follow-up were evaluated on 166 HIV-1 positive plasma samples from 126 patients. The linearity data showed a difference obtained for each point of less than 0.2 Log cp/mL. No amplification was found for the 100 HIV negative clinical specimens. The overall agreement between the two kits was 83.7 %; the differences corresponded to a slightly higher detection for the Aptima kit (with more samples detected below the lower limit of quantification). A Bland & Altman analysis of the quantifiable samples showed a mean difference of -0.05 Log and Spearman's coefficient was 0.975. Only six samples presented discrepancies (above 0.5 Log), but these differences were overall similar between the two kits. Our study has shown that the HIV1 ELITe MGB® Kit can be successfully used for the monitoring of patients infected with various epidemic HIV-1 strains, and for the precise quantification of the viral load.

In vitro replicative potential of an HIV-1/MO intergroup recombinant virus compared to HIV-1/M and HIV-1/O parental viruses.

Genetic recombination is one of the major evolution processes of HIV-1. Despite their great genetic divergence, HIV-1 groups M and O can generate HIV-1/MO intergroup recombinants. The current description of 20 HIV-1/MO unique recombinant forms suggests a possible benefit of the recombination. The aim of this work was to study in vitro the replicative potential of HIV-1/MO recombinant forms. This analysis was based on a simple recombination pattern, [Ogag/pol-Menv], harboring a breakpoint in Vpr. A chimeric infectious molecular clone, pOM-TB-2016 was synthesized from HIV-1/M subtype B and HIV-1/O subgroup T and recombinant viruses were obtained by transfection/co-culture. To compare the replicative potential of these viruses, two markers were monitored in culture supernatants: Reverse Transcriptase (RT) activity and P24 antigen concentration. The results showed a superiority of the group M parental virus compared to group O for both markers. In contrast, for the recombinant virus, RT activity data did not overlap with the concentration of P24 antigen, suggesting a hybrid behavior of the recombinant, in terms of enzyme activity and P24 production. These results highlighted many hypotheses about the impact of recombination on replicative potential and demonstrated again the significant plasticity of HIV genomes and their infinite possibility of evolution.

Evaluation of Analytical and Clinical Performance and Usefulness in a Real-Life Hospital Setting of Two in-House Real-Time RT-PCR Assays to Track SARS-CoV-2 Variants of Concern.

Since the end of 2020, multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have emerged and spread worldwide. Tracking their evolution has been a challenge due to the huge number of positive samples and limited capacities of whole-genome sequencing. Two in-house variant-screening RT-PCR assays were successively designed in our laboratory in order to detect specific known mutations in the spike region and to rapidly detect successively emerging VOCs. The first one (RT-PCR#1) targeted the 69-70 deletion and the N501Y substitution simultaneously, whereas the second one (RT-PCR#2) targeted the E484K, E484Q, and L452R substitutions simultaneously. To evaluate the analytical performance of these two RT-PCRs, 90 negative and 30 positive thawed nasopharyngeal swabs were retrospectively analyzed, and no discordant results were observed. Concerning the sensitivity, for RT-PCR#1, serial dilutions of the WHO international standard SARS-CoV-2 RNA, corresponding to the genome of an Alpha variant, were all detected up to 500 IU/mL. For RT-PCR#2, dilutions of a sample harboring the E484K substitution and of a sample harboring the L452R and E484Q substitutions were all detected up to 1000 IU/mL and 2000 IU/mL, respectively. To evaluate the performance in a real-life hospital setting, 1308 and 915 profiles of mutations, obtained with RT-PCR#1 and RT-PCR#2, respectively, were prospectively compared to next-generation sequencing (NGS) data. The two RT-PCR assays showed an excellent concordance with the NGS data, with 99.8% for RT-PCR#1 and 99.2% for RT-PCR#2. Finally, for each mutation targeted, the clinical sensitivity, the clinical specificity and the positive and negative predictive values showed excellent clinical performance. Since the beginning of the SARS-CoV-2 pandemic, the emergence of variants-impacting the disease's severity and the efficacy of vaccines and therapies-has forced medical analysis laboratories to constantly adapt to the strong demand for screening them. Our data showed that in-house RT-PCRs are useful and adaptable tools for monitoring such rapid evolution and spread of SARS-CoV-2 VOCs.

Molecular confirmation of HIV-1 and HIV-2 coinfections among initially serologically dually-reactive samples from patients living in West Africa.

OBJECTIVES: This study aimed to confirm the co-infection with HIV-1 and HIV-2, among West African patients using in-house HIV type/group enzyme-immuno assays and molecular diagnosis. DESIGN: A cross-sectional survey was conducted from April 2016 to October 2017 in the biggest HIV clinics of Côte d'Ivoire and Burkina Faso. METHOD: A first serological confirmation was done in the referral laboratory using an in-house, indirect immuno-enzymatic essay allowing the qualitative detection of both HIV-1 and HIV-2 antibodies. In order to separately detect anti-HIV-1 and anti-HIV-2 antibodies, a type/group specific enzyme-immuno assay (HIV-GSEIA) was used. To confirm the co-infections, HIV-1 and HIV-2 DNA-qualitative PCR assays were performed. RESULTS: A total of 91 patients were enrolled in the study and provided blood sample for HIV type confirmatory testing including 13 (14.3%) HIV-2 mono-reactive and 78 (85.7%) HIV-1/HIV-2 dually-reactive based on the HIV testing National Algorithms. The first serological ELISA confirmatory test performed showed that 80 (78.9%) of the 91 participants were dually-reactive. The HIV-GSEIA performed on these 80 serum samples retrieve one 61 HIV-1/HIV-2 dually-reactive samples. HIV-1 and HIV-2 DNA PCR were performed on 54 of the 61 HIV-1/HIV-2 dually-reactive samples and 46 out of 61 (75.4%) samples were found HIV-1/HIV-2 coinfected. CONCLUSION: The contribution of type/group specific enzyme-immuno assay to accurately identify HIV-1/HIV-2 coinfections remain suboptimal, emphasizing the need for molecular diagnosis platforms in West Africa, to avail HIV DNA PCR test for the confirmation of HIV-1/HIV-2 co-infections.

HIV-1 Non-Group M Strains and ART.

To eliminate HIV infection, there are several elements to take into account to limit transmission and break viral replication, such as epidemiological, preventive or therapeutic management. The UNAIDS goals of screening, treatment and efficacy should allow for this elimination if properly followed. For some infections, the difficulty is linked to the strong genetic divergence of the viruses, which can impact the virological and therapeutic management of patients. To completely eliminate HIV by 2030, we must therefore also be able to act on these atypical variants (HIV-1 non-group M) which are distinct from the group M pandemic viruses. While this diversity has had an impact on the efficacy of antiretroviral treatment in the past, recent data show that there is real hope of eliminating these forms, while maintaining vigilance and constant surveillance, so as not to allow more divergent and resistant forms to emerge. The aim of this work is therefore to share an update on the current knowledge on epidemiology, diagnosis and antiretroviral agent efficacy of HIV-1 non-M variants.

Prospective, Randomized Ponseti Treatment for Clubfoot: Orthopaedic Surgeons Versus Physical Therapists.

BACKGROUND: Clubfoot is a common congenital foot deformity in children. The Ponseti method of serial casting has become the standard of care in clubfoot treatment. Clubfoot casting is performed in many centers by both orthopaedic surgeons and physical therapists (PTs); however, direct comparison of outcomes and complications of this treatment between these providers is limited. This study prospectively compared the outcomes of patients with clubfoot treated by these 2 groups of specialists. METHODS: Between January 2010 and December 2014, all patients under the age of 12 months with a diagnosis of clubfoot were included. Patients were randomized to an orthopaedic surgeon (MD) group or a PT group for weekly serial casting. Main outcome measures included the number of casts required to achieve correction, clinical recurrence of the deformity, and the need for additional surgical intervention. RESULTS: One hundred twenty-six infants were included in the study. Patient demographics and characteristics (sex, race, family history of clubfoot, laterality, and severity of deformity) were similar between treatment groups, with the only significant difference being the mean age of entry into the study (5.2 weeks in the MD group and 9.2 weeks in the PT group, P=0.01). Mean length of follow-up was 2.6 years. The number of casts required trended to a lower number in the MD group. There was no significant difference in the rates of clinical recurrence or additional surgical intervention between groups. CONCLUSIONS: Ponseti casting for treatment of clubfoot performed by orthopaedic surgeons and PTs results in equivalent outcomes without any difference in complications. Although the number of casts required trended to a lower number in the MD group, this likely did not result in any clinical significance, as the difference in cast number equaled <1 week's difference in the overall duration of serial casting. LEVEL OF EVIDENCE: Level I-therapeutic.

Evidence of Transmission and Circulation of Deltacron XD Recombinant Severe Acute Respiratory Syndrome Coronavirus 2 in Northwest France.

In February 2022, samples collected in northwest France showed discordant molecular results. After virological and epidemiological investigations, 17 cases of Deltacron XD recombinant severe acute respiratory syndrome coronavirus 2 were confirmed by sequencing or suspected due to epidemiological links, showing evidence of an extended transmission event and circulation of this form, with low clinical severity.

Investigation of outbreak cases infected with the SARS-CoV-2 B.1.640 variant in a fully vaccinated elderly population, Normandy, France, November to December 2021.

Three confirmed infections with the SARS-CoV-2 B.1.640 variant under monitoring were reported in Normandy, north-western France in late November 2021. Investigations led to the identification of two events linked to the same cluster. A total of 75 confirmed and probable B.1.640 cases were reported. All had completed the primary vaccination series. Sixty-two cases were older than 65 years. Fifty-six cases had symptoms and four were hospitalised. This investigation provides preliminary results concerning a variant with limited information currently available.

Use of a Core Reamer for the Resection of a Central Distal Femoral Physeal Bone Bridge: A Novel Technique with 3-Year Follow-up.

A central distal femoral physeal bone bridge in a boy aged 5 years and 7 months was resected with a fluoroscopically guided core reamer placed through a lateral parapatellar approach. At 3-year follow-up, the boy's leg-length discrepancy was 3.0 cm (3.9 cm preoperatively), and the physeal bone bridge did not recur. The patient had full function and no pain or other patellofemoral complaints. This technique provided direct access to the physeal bone bridge, and complete resection was performed without injury to the adjacent physeal cartilage in the medial and lateral columns of the distal femur, which is expected to grow normally in the absence of the bridge.

Detection of numerous HIV-1/MO recombinants in France.

BACKGROUND: The broad genetic divergence of HIV-1/O relative to HIV-1/M has important implications for diagnosis, monitoring and treatment. Despite this divergence, some HIV-1/M+O dual infections and HIV-1/MO recombinant forms have been reported, mostly in Cameroon, where both groups are prevalent. Here, we describe the characteristics of such infections detected in France in 10 new patients, and discuss their implications for biological and clinical practice, owing to the presence of group O species. METHODS: The French National Reference Centre for HIV received samples within the framework of mandatory notification of HIV infections, and for expert analysis. A strategy combining serotyping, viral quantification, group-specific molecular amplification and whole-genome sequencing was used for strain characterization and complementary investigations. RESULTS: We identified one patient with M+O infection, three patients with M+O infection associated with an MO recombinant, and six patients with only an MO recombinant. These atypical infections were detected upon strain characterization (n = 4) or because of anomalies during patient monitoring (n = 6). We identified eight new URF_MO, all but one originating from Cameroon. Interestingly, two distinct recombinant strains were found in two unrelated patients, representing possible precursors of a CRF_MO. CONCLUSION: Our work highlights the fact that the continuous evolution of HIV can hinder diagnosis and complicate clinical practice. We stress that unexpected results during diagnosis or monitoring necessitate further serological and molecular exploration, these atypical infections influence biological and therapeutic management and necessitate appropriate tools, and specific surveillance is necessary, especially as the frequency of such infections may be underestimated.

HIV-1 sequences in the epidemic suggest an alternative pathway for the generation of the Long Terminal Repeats.

To generate the long-terminal repeats (LTR) that border the integrated viral genome, two-strand transfer steps must occur during reverse transcription. Analysis of the genetic polymorphisms that are present in the LTR of HIV-1 heterozygous virions in single infection cycle studies has revealed which of the two copies of genomic RNAs is used for each transfer event. Thus, the first event of strand transfer has been described to be either intra- or intermolecular, while the second event is generally intramolecular. Here, we repeated these analyses using sequences from HIV databases and extended the study to the regions surrounding the LTR. We observed a striking correlation between the pattern of recombination in the LTR and the phylogenetic origin of the surrounding sequences. This correlation suggests that the second-strand transfer can be either intra- or intermolecular and, interestingly, could reflect an effect of proximity between nucleic acids that would guide this transfer. This factor could be particularly relevant for heterozygous viruses containing highly divergent genomic RNAs, such as those considered in the present study.

The Risk of Curve Progression and Surgery in African Americans With Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective clinical cohort study. OBJECTIVE: To determine if certain risk factors (age, curve magnitude, skeletal maturity, gender, and curve pattern) traditionally associated with curve progression and surgical intervention in the general population apply equally to African Americans. SUMMARY OF BACKGROUND DATA: Currently, information is limited on the role that a patient's race plays in the risk of curve progression of adolescent idiopathic scoliosis (AIS), and existing studies have conflicting results. METHODS: Retrospective search of records identified patients who were African American, had been diagnosed with AIS, had a major curve Cobb angle of 10 degrees or more, and had at least two clinical visits with spinal radiographs at least 90 days apart to determine the risk factors for surgical treatment, and 2 years apart to determine the risk factors for curve progression. Patients with a medical condition likely to cause scoliosis were excluded. RESULTS: Of 738 African American patients with AIS, 223 were assessed for surgical risk factors, and 72 were assessed for curve progression risk factors. Fifty-six (29.17%) had progression of the major coronal curve, and 38 (17.04%) underwent surgery. Age at presentation and curve magnitude at presentation were significant risk factors for surgical intervention. Curve magnitude at presentation was a significant risk factor for curve progression. No significant relationships were found for gender or curve type as they relate to surgical intervention or curve progression. CONCLUSION: Age and curve magnitude at presentation were significantly associated with surgery, as is true in other scoliosis populations. Curve magnitude at presentation was associated with curve progression. In contrast to studies in other populations, however, no significant association was observed between curve progression and age at presentation, curve type, or gender, or between surgery and curve type or gender. LEVEL OF EVIDENCE: Level III, prognostic cohort study.

Benign Natural History of Spondylolysis in Adolescence With Midterm Follow-Up.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: To use the Micheli Functional Scale to assess adolescent patients with spondylolysis treated conservatively at midterm follow-up. SUMMARY OF BACKGROUND: Spondylolysis is a common source of back pain for adolescents and is generally managed with bracing and physical therapy. There is little data regarding the results of conservative management of spondylolysis over time. METHODS: Four major academic pediatric institutions performed a retrospective chart review of patients from 5 to 21 years of age with the initial diagnosis of spondylolysis. Inclusion criteria were patients who initially underwent conservative management and had a minimum of 2 years' follow-up. The patients were contacted and asked to complete the Micheli Functional Scale Survey. RESULTS: A total of 295 patients with the diagnosis of spondylolysis were identified and contacted. Sixty-one subjects with spondylolysis completed the follow-up survey. Sixty of 61 respondents (98%) answered questions regarding their current pain level. Thirty-five of 60 (58.3%) reported no pain (0/10) and 47/60 (78%) rated their pain at 3 or less, whereas 22% (13/60) rated their pain as 4 or higher. There was no correlation with pain ratings on the follow-up survey and radiographic healing at initial management. Of the 61 patients, 50 returned to sports (82%), 8 did not return (13%), and 5 returned to most but not all of their sports (8%). No correlation was observed between radiographic healing and return to sports (p = .4885). CONCLUSION: Using a validated functional scale, this study demonstrated that with conservative management of spondylolysis a majority of patients at an average of 8 years out self-report a return to sports (90%), though many reported continued pain (42%) and interference with activities (67%). There was no correlation observed between radiographic evidence of healing and pain or return to sports with a mean follow-up of 8 years. LEVEL OF EVIDENCE: Multicenter retrospective case series.

Use of Vertical Expandable Prosthetic Titanium Rib (VEPTR) in the Treatment of Congenital Scoliosis Without Fused Ribs.

BACKGROUND: Although the vertical expandable prosthetic titanium rib (VEPTR) has been shown to be useful in treating congenital scoliosis (CS) with fused ribs, no studies to date have specifically evaluated the efficacy of VEPTR in the treatment of CS without fused ribs. The purpose of this study was to determine the effectiveness of VEPTR in sagittal/coronal curve correction and spine growth and compare its complication rate to the use of VEPTR in other conditions and to other treatment methods used for CS. METHODS: A multicenter database was queried for patients with CS without fused ribs treated with VEPTR. Anteroposterior (AP) and lateral radiographs were used to measure parameters at 3 timepoints (preoperative, immediate postoperative, and latest follow-up): coronal Cobb angle, sagittal kyphosis, and thoracic and lumbar spine heights. Clinical data included age, time to follow-up, and complications. RESULTS: Twenty-five patients (13 females, 12 males) were identified. The average age at implantation was 5.7 years, with an average follow-up of 50 months. Several parameters improved from preoperative to latest follow-up: coronal Cobb angle (69 to 54 degrees, P<0.0001), thoracic spine height (T1-T12) in the AP (13.3 to 15.9 cm, P<0.0001) and lateral (14.8 to 17.4 cm, P=0.0024) planes, and lumbar spine height (L1-S1) in the AP (8.8 to 11.4 cm, P<0.0001) and lateral (9.9 to 11.9 cm, P=0.0002) planes. Kyphosis increased over the study period (36 to 41 degrees, P=0.6). Fifteen patients (60%) had 41 complications (average 2.75; range, 1 to 12). Twenty-eight complications (68%) were device-related, and 13 (32%) were disease-related. The most common complications were infection, wound dehiscence, and device migration. Six complications (15%) altered the course of treatment. Thoracic spine height increased 79% of expected growth. CONCLUSION: VEPTR is an effective treatment for patients with CS without fused ribs, as evidenced by improved radiographic parameters and increased spinal height, with a complication rate which is high but similar to other methods of treatment. LEVEL OF EVIDENCE: Level IV-case series.

Fracture of the Medial Humeral Epicondyle in Children: A Comparison of Operative and Nonoperative Management.

To compare clinical and radiographic outcomes of medial epicondylar fractures treated operatively to those treated nonoperatively, 30 patients with 31 fractures were divided into three groups: (a) nondisplaced, six treated nonoperatively; (b) incarcerated fragment, four with operative treatment; and (c) displaced but not incarcerated, 21 fractures, 14 treated operatively and seven nonoperatively. Clinical outcomes were assessed with follow-up examination and the Japanese Orthopaedic Association elbow assessment score. Average elbow scores were 98 in nondisplaced fractures, 94 with an incarcerated fragment, 95 in displaced fractures treated operatively, and 94 in displaced fractures treated nonoperatively. The only nonunion was in a fracture with an incarcerated fragment. Both operative and nonoperative treatment produced good outcome scores in displaced but not incarcerated fractures, but radiographic deformity and instability were more frequent in those treated nonoperatively.

Transverse fractures of the femoral shaft are a better predictor of nonaccidental trauma in young children than spiral fractures are.

BACKGROUND: Certain fracture configurations, especially spiral fractures, are often thought to be indicative of nonaccidental trauma in children. The purpose of this study was to determine whether femoral fracture morphology, as determined by an objective measurement (fracture ratio), was indicative of nonaccidental trauma in young children. METHODS: Consecutive patients who were three years of age or younger and had a closed, isolated femoral shaft fracture treated at an urban pediatric level-I trauma center between 2005 and 2013 were identified. Anteroposterior and lateral fracture ratios (fracture length/bone diameter) were calculated for each patient by a fellowship-trained pediatric orthopaedic surgeon who was blinded to the patient's clinical history. The presence or absence of a Child Protective Services referral as well as institutional Child Assessment Program evaluations were reviewed. Nonaccidental trauma was deemed to be present, absent, or indeterminate by Child Protective Services or an on-site Child Assessment Program team. To further evaluate and quantify the likelihood of nonaccidental trauma, the criteria of the Modified Maltreatment Classification System were used. RESULTS: Of 122 patients identified, ninety-five met the inclusion criteria for this study. Of these ninety-five, fifty-one (54%) had either a Child Protective Services or a Child Assessment Program consultation because of suspected nonaccidental trauma. Thirteen (25%) were found to have nonaccidental trauma as determined by Child Protective Services or the Child Assessment Program team and seven (14%) had indeterminate Child Protective Services or Child Assessment Program investigations. All thirteen patients with nonaccidental trauma, as well as the seven patients with an indeterminate Child Protective Services or Child Assessment Program investigation, had positive Modified Maltreatment Classification System scores for physical abuse. Patients who had nonaccidental trauma had significantly decreased mean anteroposterior fracture ratios compared with those who had confirmed accidental trauma (p < 0.0001). CONCLUSIONS: The fracture ratio can be helpful to determine fracture morphology and can be used as part of the assessment of a child with suspected nonaccidental trauma. While not diagnostic, the presence of a transverse diaphyseal femoral fracture in a young child should raise the index of suspicion for nonaccidental trauma. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.