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Background: Meniscal allograft transplantation (MAT) has been shown to provide clinical benefits in patients with symptomatic meniscal deficiency in the short term and midterm. There is, however, a paucity of data regarding long-term outcomes after MAT using fresh-frozen allografts and the bridge-in-slot technique. Purpose: To report clinical outcomes and revision rates after primary MAT with fresh-frozen allografts and the bridge-in-slot technique in a large case series of patients at a 10-year minimum follow-up. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review of prospectively collected data was performed on patients undergoing primary MAT between 2001 and 2012. Lysholm, International Knee Documentation Committee subjective form, and Knee injury and Osteoarthritis Outcome Score subscales were collected preoperatively and at 1-, 2-, 5-, and minimum 10-year follow-ups. Cox proportional hazards modeling was used to identify variables associated with reoperation and failure, defined as revision MAT or conversion to arthroplasty. Reoperation was defined as a subsequent surgical intervention on the transplanted meniscus, including partial or total meniscectomy, meniscal repair, or failure as defined in the previous sentence. Results: A total of 174 patients undergoing MAT met the inclusion criteria and were followed for a mean of 12.7 ± 2.7 years (range, 10.0-21.0 years). The mean age at surgery was 28.3 ± 10.1 years. The patients were predominantly female (n = 92; 53%), and medial MAT was the most commonly performed procedure (n = 91; 52%). Concomitant procedures were performed in 115 patients (66%), with the most common procedure being osteochondral allograft transplantation (n = 59; 34%). Patients demonstrated statistically significant postoperative improvements at all time points for all patient-reported outcome measures ( P ≤ .0001). A total of 65 patients (37%) underwent a meniscal reoperation at a mean time of 6.6 ± 5.5 years (range, 0.3-16.7 years) postoperatively. A total of 40 patients (23%) met the criteria for failure at a mean time of 7.3 ± 5.0 years (range, 1.0-17.4 years) after MAT, with 22 of these patients having undergone a previous meniscal reoperation. At the final follow-up, 13 patients (7%) had undergone revision MAT and 27 (15%) had converted to arthroplasty. The MAT survival rates free of meniscal reoperation and failure were 73% and 85% at 10 years and 60% and 72% at 15 years, respectively. At the time of the final follow-up, 86% of patients reported that they were satisfied with their overall postoperative condition. Conclusion: Primary MAT demonstrates efficacy and durability with high rates of patient satisfaction at a minimum 10-year follow-up. Patients should be counseled that although reoperation rates may approach 40% at 15 years, rates of overall revision MAT and conversion to arthroplasty remain low at long-term follow-up.

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

Background/aims There has been growing interest in better understanding the potential of observational research methods in medical product evaluation and regulatory decision-making. Previously, we used linked claims and electronic health record data to emulate two ongoing randomized controlled trials, characterizing the populations and results of each randomized controlled trial prior to publication of its results. Here, our objective was to compare the populations and results from the emulated trials with those of the now-published randomized controlled trials. Methods This study compared participants’ demographic and clinical characteristics and study results between the emulated trials, which used structured data from OptumLabs Data Warehouse, and the published PRONOUNCE and GRADE trials. First, we examined the feasibility of implementing the baseline participant characteristics included in the published PRONOUNCE and GRADE trials’ using real-world data and classified each variable as ascertainable, partially ascertainable, or not ascertainable. Second, we compared the emulated trials and published randomized controlled trials for baseline patient characteristics (concordance determined using standardized mean differences <0.20) and results of the primary and secondary endpoints (concordance determined by direction of effect estimates and statistical significance). Results The PRONOUNCE trial enrolled 544 participants, and the emulated trial included 2226 propensity score-matched participants. In the PRONOUNCE trial publication, one of the 32 baseline participant characteristics was listed as an exclusion criterion on ClinicalTrials.gov but was ultimately not used. Among the remaining 31 characteristics, 9 (29.0%) were ascertainable, 11 (35.5%) were partially ascertainable, and 10 (32.2%) were not ascertainable using structured data from OptumLabs. For one additional variable, the PRONOUNCE trial did not provide sufficient detail to allow its ascertainment. Of the nine variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 6 (66.7%). The primary endpoint of time from randomization to the first major adverse cardiovascular event and secondary endpoints of nonfatal myocardial infarction and stroke were concordant between the emulated trial and published randomized controlled trial. The GRADE trial enrolled 5047 participants, and the emulated trial included 7540 participants. In the GRADE trial publication, 8 of 34 (23.5%) baseline participant characteristics were ascertainable, 14 (41.2%) were partially ascertainable, and 11 (32.4%) were not ascertainable using structured data from OptumLabs. For one variable, the GRADE trial did not provide sufficient detail to allow for ascertainment. Of the eight variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 4 (50.0%). The primary endpoint of time to hemoglobin A1c ≥7.0% was mostly concordant between the emulated trial and the published randomized controlled trial. Conclusion Despite challenges, observational methods and real-world data can be leveraged in certain important situations for a more timely evaluation of drug effectiveness and safety in more diverse and representative patient populations.

Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS). Patients and Methods: Patients enrolled in 17 first-line clinical trials, who had mCRC with ≥ 2 lesions at baseline, and a restaging scan by 12 weeks were included. For each patient, lesions were categorized as a progressing lesion (PL: > 20% increase in the longest diameter (LD)), responding lesion (RL: > 30% decrease in LD), or stable lesion (SL: neither PL nor RL) based on the 12-week scan. Lesion-based response criteria were defined for each patient as follows: PL only, SL only, RL only, and varied responses (mixture of RL, SL, and PL). Lesion-based response criteria and OS were correlated using stratified multivariable Cox models. The concordance between OS and classifications was measured using the C statistic. Results: Among 10,551 patients with mCRC from 17 first-line studies, varied responses were noted in 51.6% of patients, among whom, 3.3% had RL/PL at 12 weeks. Among patients with RL/SL, 52% had stable disease (SD) by RECIST 1.1, and they had a longer OS (median OS (mOS) = 19.9 months) than those with SL only (mOS = 16.8 months, HR (95% CI) = 0.81 (0.76, 0.85), p < 0.001), although a shorter OS than those with RL only (mOS = 25.8 months, HR (95% CI) = 1.42 (1.32, 1.53), p < 0.001). Among patients with SL/PL, 74% had SD by RECIST 1.1, and they had a longer OS (mOS = 9.0 months) than those with PL only (mOS = 8.0 months, HR (95% CI) = 0.75 (0.57, 0.98), p = 0.040), yet a shorter OS than those with SL only (mOS = 16.8 months, HR (95% CI) = 1.98 (1.80, 2.18), p < 0.001). These associations were consistent across treatment regimen subgroups. The lesion-based response criteria showed slightly higher concordance than RECIST 1.1, although it was not statistically significant. Conclusion: Varied responses at first restaging are common among patients receiving first-line therapy for mCRC. Our lesion-based measurement criteria allowed for better mortality discrimination, which could potentially be informative for treatment decision-making and influence patient outcomes.

This report addresses the time dependence of normal biomedical processes. The conception rate in humans shows relationships that strikingly coincide with planetary periodicities like the orbital period of Jupiter, the 11 years solar cycle and the 237 days Jupiter–Venus synod, and the combined dependence on Jupiter with Mars’ orbital position. The birth rates are used as conception surrogates based on a data set available from the Minnesota Department of Health. The statistical significance of each independent analysis (far) exceeds 5[Formula: see text]. This result cannot be explained with known science. As with other observations in Physics and Medicine (i.e., melanoma), tentatively the only viable explanation we have is the otherwise invisible streaming matter from the dark Universe we live in. The favored dark matter scenario involves streams or clusters as opposed to an isotropic dark sector. The dark Universe scenario has been the driving idea for this type of work. The high sensitivity of living matter to the tiniest external impact might help identify the nature of the dark matter particles, a major problem in all physics since the 1930s. This work is a model for evaluating other biological processes and mutation rates.

Background Pathogenic variants in the zinc finger protein coding genes are rare causes of intellectual disability and congenital malformations. Mutations in the ZNF148 gene causing GDACCF syndrome (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies; MIM #617260) have been reported in five individuals so far. Methods As a result of an international collaboration using GeneMatcher Phenome Central Repository and personal communications, here we describe the clinical and molecular genetic characteristics of 22 previously unreported individuals. Results The core clinical phenotype is characterised by developmental delay particularly in the domain of speech development, postnatal growth retardation, microcephaly and facial dysmorphism. Corpus callosum abnormalities appear less frequently than suggested by previous observations. The identified mutations concerned nonsense or frameshift variants that were mainly located in the last exon of the ZNF148 gene. Heterozygous deletion including the entire ZNF148 gene was found in only one case. Most mutations occurred de novo, but were inherited from an affected parent in two families. Conclusion The GDACCF syndrome is clinically diverse, and a genotype-first approach, that is, exome sequencing is recommended for establishing a genetic diagnosis rather than a phenotype-first approach. However, the syndrome may be suspected based on some recurrent, recognisable features. Corpus callosum anomalies were not as constant as previously suggested, we therefore recommend to replace the term ‘GDACCF syndrome’ with ‘ZNF148-related neurodevelopmental disorder’.

OBJECTIVE Compared with laminectomy with posterior cervical fusion (PCF), cervical laminoplasty (CL) may result in different outcomes for those operated on for cervical spondylotic myelopathy (CSM). The aim of this study was to compare 24-month patient-reported outcomes (PROs) for laminoplasty versus PCF by using the Quality Outcomes Database (QOD) CSM data set. METHODS This was a retrospective study using an augmented data set from the prospectively collected QOD Registry Cervical Module. Patients undergoing laminoplasty or PCF for CSM were included. Using the nearest-neighbor method, the authors performed 1:1 propensity matching based on age, operated levels, and baseline modified Japanese Orthopaedic Association (mJOA) and visual analog scale (VAS) neck pain scores. The 24-month PROs, i.e., mJOA, Neck Disability Index (NDI), VAS neck pain, VAS arm pain, EQ-5D, EQ-VAS, and North American Spine Society (NASS) satisfaction scores, were compared. Only cases in the subaxial cervical region were included; those that crossed the cervicothoracic junction were excluded. RESULTS From the 1141 patients included in the QOD CSM data set who underwent anterior or posterior surgery for cervical myelopathy, 946 (82.9%) had 24 months of follow-up. Of these, 43 patients who underwent laminoplasty and 191 who underwent PCF met the inclusion criteria. After matching, the groups were similar for baseline characteristics, including operative levels (CL group: 4.0 ± 0.9 vs PCF group: 4.2 ± 1.1, p = 0.337) and baseline PROs (p > 0.05), except for a higher percentage involved in activities outside the home in the CL group (95.3% vs 81.4%, p = 0.044). The 24-month follow-up for the matched cohorts was similar (CL group: 88.4% vs PCF group: 83.7%, p = 0.534). Patients undergoing laminoplasty had significantly lower estimated blood loss (99.3 ± 91.7 mL vs 186.7 ± 142.7 mL, p = 0.003), decreased length of stay (3.0 ± 1.6 days vs 4.5 ± 3.3 days, p = 0.012), and a higher rate of routine discharge (88.4% vs 62.8%, p = 0.006). The CL cohort also demonstrated a higher rate of return to activities (47.2% vs 21.2%, p = 0.023) after 3 months. Laminoplasty was associated with a larger improvement in 24-month NDI score (−19.6 ± 18.9 vs −9.1 ± 21.9, p = 0.031). Otherwise, there were no 3- or 24-month differences in mJOA, mean NDI, VAS neck pain, VAS arm pain, EQ-5D, EQ-VAS, and distribution of NASS satisfaction scores (p > 0.05) between the cohorts. CONCLUSIONS Compared with PCF, laminoplasty was associated with decreased blood loss, decreased length of hospitalization, and higher rates of home discharge. At 3 months, laminoplasty was associated with a higher rate of return to baseline activities. At 24 months, laminoplasty was associated with greater improvements in neck disability. Otherwise, laminoplasty and PCF shared similar outcomes for functional status, pain, quality of life, and satisfaction. Laminoplasty and PCF achieved similar neck pain scores, suggesting that moderate preoperative neck pain may not necessarily be a contraindication for laminoplasty.

OBJECTIVE Ulnar neuropathy at the elbow (UNE) is common, affecting 1%–6% of the population. Despite this, there remains a lack of consensus regarding optimal treatment. This is primarily due to the difficulty one encounters when trying to assess the literature. Outcomes are inconsistently reported, which makes comparing studies or developing meta-analyses difficult or even impossible. Thus, there is a need for a core outcome set (COS) for UNE (COS-UNE) to help address this problem. The objective of this study was to utilize a modified Delphi method to develop COS-UNE. METHODS A 5-stage approach was utilized to develop COS-UNE: stage 1, consortium development; 2, literature review to identify potential outcome measures; 3, Delphi survey to develop consensus on outcomes for inclusion; 4, Delphi survey to develop definitions; and 5, consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations. RESULTS The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 21 participants, all neurological surgeons representing 11 countries. The final COS-UNE consisted of 22 data points/outcomes covering the domains of demographic characteristics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 6 months, with the consensus optimal timepoints for assessment identified as preoperatively and 3, 6, and 12 months postoperatively. CONCLUSIONS The authors identified consensus data points/outcomes and also provided definitions and specific scales to be utilized to help ensure that clinicians are consistent in their reporting across studies on UNE. This COS should serve as a minimum set of data to be collected in all future neurosurgical studies on UNE. The authors hope that clinicians evaluating ulnar neuropathy will incorporate this COS into routine practice and that future studies will consider this COS in the design phase.

Acute kidney injury (AKI) survivors have a dynamic posthospital course which warrants close monitoring. Remote patient monitoring (RPM) could be used to improve quality and efficiency of AKI survivor care. Objective: The objective of this report was to describe the development and preliminary feasibility of an AKI RPM program launched in October 2021. Setting: Academic medical center. Patients: Patients enrolled in the AKI RPM program were those who experienced AKI during a hospitalization and underwent nephrology consultation. Measurements/Methods: At enrollment, patients were provided with home monitoring technology and underwent weekly laboratory assessments. Nurses evaluated the data daily and adhered to prespecified protocols for management and escalation of care if needed. Results: Twenty patients were enrolled in AKI RPM in the first 5 months. Median duration of program participation was 36 (31, 40) days. Eight patients (40%) experienced an unplanned readmission, or an emergency department visit, half (N = 4) of which were attributed to AKI and related circumstances. Of the 9 postgraduation survey respondents, all were satisfied with the RPM program and 89% would recommend RPM to other patients with similar health conditions. Limitations: Acute kidney injury RPM was made possible by the existing infrastructure in our integrated health system and the robust resources available in the Mayo Clinic Center for Digital Health. Such infrastructure may not be universally available which could limit scale and generalizability of such a program. Conclusions: Remote patient monitoring can offer a unique opportunity to bridge the care transition from hospital to home and increase access to quality care for the AKI survivors.