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ImportanceLate-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm.ObjectiveTo report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months’ corrected age.Design, Setting, and ParticipantsThis cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks’ gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers.ExposuresCulture-confirmed LOM.Main Outcomes and MeasuresIncidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021).ResultsAmong 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 (P < .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 (P < .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P < .001) and among those with culture-confirmed LOS (23%-79%, P < .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus, 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection.Conclusions and RelevanceIn this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.

Background: Biomechanical studies support the use of suture tape reinforcement for limiting graft elongation and increasing strength in knee ligament reconstructions. Purpose: To compare posterior cruciate ligament (PCL) laxity, complication and reoperation rates, and patient-reported outcomes (PROs) after all-inside single-bundle PCL reconstruction (PCLR) with versus without independent suture tape reinforcement. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective cohort study of consecutive patients who underwent primary, all-inside allograft single-bundle PCLR with and without independent suture tape reinforcement at a single academic institution from 2012 to 2019. Medical records were reviewed for patient characteristics, additional injuries, and concomitant procedures. PRO scores (including the International Knee Documentation Committee [IKDC], Tegner activity scale, and Lysholm scores), bilateral comparison kneeling radiographs, and physical examination findings were collected at a minimum of 2 years postoperatively. Results: Included were 50 patients: 19 with suture tape reinforcement (mean age 30.6 ± 2.9 years) and 31 without suture tape reinforcement (control group; mean age 26.2 ± 1.6 years). One PCLR graft in the suture tape group failed. Posterior drawer examination revealed grade 1+ laxity in 4 of 19 (21%) of the suture tape cohort versus 6 of 31 (19%) of the control cohort ( P > .999). Bilateral kneeling radiographs showed similar side-to-side differences in laxity between the groups (suture tape vs control: mean, 1.9 ± 0.4 vs 2.6 ± 0.6 mm; P = .361). There were no statistically significant differences between the groups in postoperative IKDC (suture tape vs control: 79.3 vs 79.6; P = .779), Lysholm (87.5 vs 84.3; P = .828), or Tegner activity (5.6 vs 5.7; P = .562) scores. Conclusion: All-inside single-bundle PCLR with and without independent suture tape reinforcement demonstrated low rates of graft failure, complications, and reoperations, with satisfactory PROs at a minimum 2-year follow-up. Radiographic posterior tibial translation was comparable between the 2 groups.

Background: Some surgeons are now considering fixation of traumatic chondral-only fragments in juvenile knees, but few data remain to guide treatment. Purpose: To determine if surgical fixation of chondral-only fragments in the juvenile knee results in an adequate healing response with successful imaging and clinical outcomes. Study Design: Case series; Level of evidence, 4. Methods: Data were collected on 16 skeletally immature patients treated with fixation of chondral-only fragments with a minimum 1-year follow-up. Patients were selected by the operating surgeons based on the quality and size of the chondral fragment. Demographic data, lesion characteristics, surgical procedure details, complications, and postoperative imaging were assessed. Validated outcome measures were collected pre- and postoperatively and included the following scores: International Knee Documentation Committee (IKDC), Marx Activity Scale, Knee injury and Osteoarthritis Outcome Score (KOOS), Hospital for Special Surgery Pediatric Functional Activity–Brief Scale (HSS Pedi-FABS), Patient-Reported Outcomes Measurement Information System (PROMIS)–Physical Health and PROMIS–Psychological Health, and Tegner. Results: The mean age of our patient cohort was 14.9 years. The mean size of the repaired defects measured 3.2 cm 2 . Injury sites included the patella (n = 1), medial femoral condyle (n = 3), trochlea (n = 4), and lateral femoral condyle (n = 8). Within the mean follow-up time of 42.3 months (range, 15-145), there was 1 clinical failure with loosening of the chondral fragment and the need for reoperation. At a mean follow-up of 3.5 years, the mean (interquartile range) patient-reported outcome scores were as follows: IKDC, 95.2 (94.3-100); Marx Activity Scale, 11.5 (11.5-16); KOOS, 95.81 (93.5-95.81); HSS Pedi-FABS, 16.94 (11.5-26); PROMIS–Physical Health, 93.75% (90%-100%); PROMIS–Psychological Health, 90% (88.75%-100%); and Tegner, 5.69 (4.75-7). All patients who were engaged in sports before injury returned to the same or higher level of competition with the exception of 1 patient. Conclusion: Primary repair of chondral-only injuries with internal fixation can be a successful treatment option in selected patients. Clinical and imaging results at final follow-up suggest that reintegration of the cartilage fragment is achievable and leads to excellent clinical function and a high return-to-sports rate.

Antimicrobial resistance (AMR) is a well-known global threat due to the subsequent increase in antimicrobial usage. Several antimicrobial stewardship (AMS) strategies have been implemented to curb irrational prescribing and reduce the AMR burden. However, since the beginning of the COVID-19 pandemic, it has enormously impacted the healthcare system and jeopardized public health, causing millions of deaths globally. Our semi-structured qualitative study aimed to explore the impact of COVID-19 on AMS activities in the UK hospitals. Seventeen interviews were conducted with health care professionals who were part of AMS teams (consultant medical microbiologists, infectious disease consultants, antimicrobial pharmacists). Interviews were audio-recorded and transcribed. An inductive thematic framework was adopted to analyse and create the themes. After agreement of the hierarchical framework definition, all transcripts were coded accordingly. Four main themes and 15 sub-themes were identified. These main themes were: (1) AMS activities or strategies before and during the pandemic; (2) challenges to implementing AMS activities before and during the pandemic; (3) information from public authorities on AMS during the pandemic; and (4) new AMS activities/strategies adopted during the pandemic. Staff vacancies, redeploying of AMS staff to other duties and meeting the burden related to the COVID-19 and lack of resources were the most frequently identified contributing factors to withheld AMS activities during the pandemic. However, modifications to the hybrid working environment, i.e., remote or flexible working, allowed for resumption of AMS activities including virtual ward rounds, virtual meetings and other activities. Further research needs to assess the impact of the hybrid delivery system on AMS activities.

Abstract Study Objectives Isolated REM sleep behavior disorder (iRBD) carries a high lifetime risk for phenoconversion to a defined neurodegenerative disease (NDD) including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. We aimed to examine iRBD patient values and preferences regarding prognostic counseling. Methods One hundred thirteen iRBD patient participants enrolled in the Mayo Clinic iRBD Patient Registry were sent an email survey concerning their values and preferences concerning NDD prognostic counseling and their experiences following diagnosis with iRBD. Results Of 81 respondents (71.7% response rate), the majority were men (74.0%) with an average age of 65.7 (±9.7) years. Responses indicated a strong preference toward receiving prognostic information about possible future NDD development. 92.5% of respondents felt knowledge concerning personal NDD risk was important, while 87.6% indicated prognostic discussions were important to maintaining trust in their physician. 95.7% indicated a desire for more information, while only 4.3% desired less information regarding their NDD prognostic risk. Most respondents strongly agreed that prognostic information was important to discuss with their family and friends and inform future life planning, and most expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia. Conclusions Most iRBD patients indicated strong preferences for disclosure of NDD prognostic risk and indicated that prognostic information was important for family discussions and future life planning. Future broader surveys and qualitative studies of clinic-based and ultimately community dwelling iRBD patients’ values and preferences are needed to guide appropriately tailored and individualized prognostic counseling approaches following iRBD diagnosis.

Risk of sudden death in multiple system atrophy (MSA) is greatest during sleep with unknown mechanisms. We compared nocturnal pulse event frequency in 46 MSA patients and age‐/sex‐matched controls undergoing overnight pulse oximetry. Nocturnal oxyhemoglobin desaturation indices and pulse event indices (PEIs) were recorded, and relationships between pulse oximetry variables and survival were analyzed. MSA patients had lower PEI (3.1 ± 5.3 vs. 12.8 ± 10.8, p < 0.001) despite greater hypoxic burden and similar frequency of respiratory events. Nocturnal pulse events were not associated with severity of daytime autonomic failure. Two MSA patients had suspected sudden death, both with severely reduced PEI. MSA patients have fewer nocturnal pulse events compared with controls, despite similar respiratory event frequency, suggesting abnormal cardiac responses to sleep‐disordered breathing. Whether this contributes to sudden death in MSA requires further study. ANN NEUROL 2023;93:205–212

AbstractBackgroundKnown risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.MethodsSingle nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer–related cell types.ResultsWe identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P &lt; .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P &lt; .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types.ConclusionsCNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.