Citations

OBJECTIVE Proximal junctional kyphosis (PJK) is a complication of surgical management for adult spinal deformity (ASD) with a multifactorial etiology. Many risk factors are controversial, and their relative importance is not fully understood. The authors aimed to elucidate the association between bone mineral density (BMD) and PJK. METHODS A systematic literature search was performed using PubMed and Web of Science keywords of "Proximal Junctional Kyphosis [MeSH] OR Proximal Junctional Failure [MeSH]" AND "Bone Mineral Density [MeSH] OR Hounsfield Units [MeSH] OR DEXA [MeSH]" set to the date range of January 2002 to July 2022. Studies required a minimum of 10 patients and 12 months of follow-up. Articles were included if they were in the English language and presented a primary retrospective cohort that included a comparison of patients with and without PJK, as well as a radiographic biomarker for BMD, such as Hounsfield units (HU) or T-score. RESULTS A total of 18 unique studies with 2185 patients who underwent ASD surgery were identified. Of these, 537 patients (24.6%) developed PJK. Eight studies provided T-scores that were amenable to comparison, which found that patients who developed PJK were found to have lower BMD T-scores by a mean of −0.69 (95% CI −0.88 to −0.50; I 2 = 63.9%, p < 0.001). The HU at the UIV among patients with the PJK group (n = 101) compared with the non-PJK group (n = 156) was found to be significantly lower (mean difference −32.35, 95% CI −46.05 to −18.65; I 2 = 28.7%, p < 0.001). CONCLUSIONS This meta-analysis suggests that low preoperative BMD as measured by T-score and a diagnosis of osteoporosis were associated with higher postoperative PJK. Additionally, lower HU on CT at the UIV were found to be significant risk factors for postoperative PJK as well. These findings suggest that more attention to preoperative BMD is a risk factor for PJK among ASD patients is warranted.

Background The MIVI Q aspiration catheters have been shown to achieve significantly greater flow rates than other intracranial aspiration catheters in vitro. We describe our initial real-world experience with the MIVI Q catheter in emergent acute ischemic stroke (AIS) caused by distal and medium vessel occlusions (DMVO). Methods Data was collated from a prospectively maintained database which included patients from October 2019 to December 2022. Occlusion demographics, thrombectomy technique, reperfusion scoring, procedural complications and disposition were assessed. The primary outcome of interest was rate of successful reperfusion defined as thrombolysis in cerebral infarction (TICI) score 2b-3. Secondary outcomes included rate of first pass effect (FPE) and complications. Results We included 64 target occlusions in 51 patients. The Q catheter successfully reached the DMVO in all occlusions. Successful reperfusion was achieved in 49/64 (76.6%) occlusions, and TICI scores were similar for primary and secondary DMVOs (P value = 0.41). FPE was achieved in 39/64 (60.9%) occlusions and did not differ between primary and secondary DMVOs (P value = 0.13). Reperfusion hemorrhage occurred in 3/64 (4.7%) cases, small volume subarachnoid hemorrhage in 3/64 (4.7%) cases, and small hemorrhagic transformation in 1/64 (1.6%) cases; the rate of complications did not differ based on primary versus secondary DMVO (P value = 0.29). Conclusion The MIVI Q catheter is both safe and effective. Our real-world experience supports the superior flow rates demonstrated in vitro and translates into high rates of successful reperfusion in AIS caused by DMVO in clinical practice.

Abstract Purpose: Mucosal melanoma is a rare, aggressive form of melanoma with extremely high recurrence rates despite definitive surgical resection with curative intent. Currently there is no consensus on adjuvant therapy. Data on checkpoint inhibitors for adjuvant therapy are lacking. Patients and Methods: We performed a single-arm, multicenter clinical trial using “flip dose” ipilimumab (1 mg/kg q3w × 4 cycles), and nivolumab (3 mg/kg q3w × 4 cycles), then nivolumab 480 mg q4w × 11 cycles to complete a year of adjuvant therapy. Participants must have had R0/R1 resection ≤90 days before registration, no prior systemic therapy (adjuvant radiotherapy allowed), ECOG 0/1, and no uncontrolled autoimmune disease or other invasive cancer. Patients were recruited through the Midwest Melanoma Partnership/Hoosier Oncology Network. Results: From September 2017 to August 2021, 35 patients were enrolled. Of these, 29 (83%) had R0 resections, and 7 (20%) received adjuvant radiotherapy. Median age was 67 years, 21 (60.0%) female. Recurrence-free survival (RFS) rates at 1 and 2 years were 50% [95% confidence interval (CI), 31%–66%] and 37% (95% CI, 19%–55%), respectively. Overall survival rates at 1 and 2 years were 87% (95% CI, 68%–95%) and 68% (95% CI, 46%–83%), respectively. Median RFS was 10.3 months (95% CI, 5.7–25.8). Most common grade 3 toxicities were diarrhea (14%), hypertension (14%), and hyponatremia (11%), with no grade 4/5 toxicities. Conclusions: Flip-dose ipilimumab and nivolumab after resection of mucosal melanoma is associated with outcomes improved over that of surgical resection alone. Long-term follow-up, subgroup analyses and correlative studies are ongoing.

OBJECTIVE Depression and anxiety are associated with inferior outcomes following spine surgery. In this study, the authors examined whether patients with cervical spondylotic myelopathy (CSM) who have both self-reported depression (SRD) and self-reported anxiety (SRA) have worse postoperative patient-reported outcomes (PROs) compared with patients who have only one or none of these comorbidities. METHODS This study is a retrospective analysis of prospectively collected data from the Quality Outcomes Database CSM cohort. Comparisons were made among patients who reported the following: 1) either SRD or SRA, 2) both SRD and SRA, or 3) neither comorbidity at baseline. PROs at 3, 12, and 24 months (scores for the visual analog scale [VAS] for neck pain and arm pain, Neck Disability Index [NDI], modified Japanese Orthopaedic Association [mJOA] scale, EQ-5D, EuroQol VAS [EQ-VAS], and North American Spine Society [NASS] patient satisfaction index) and achievement of respective PRO minimal clinically important differences (MCIDs) were compared. RESULTS Of the 1141 included patients, 199 (17.4%) had either SRD or SRA alone, 132 (11.6%) had both SRD and SRA, and 810 (71.0%) had neither. Preoperatively, patients with either SRD or SRA alone had worse scores for VAS neck pain (5.6 ± 3.1 vs 5.1 ± 3.3, p = 0.03), NDI (41.0 ± 19.3 vs 36.8 ± 20.8, p = 0.007), EQ-VAS (57.0 ± 21.0 vs 60.7 ± 21.7, p = 0.03), and EQ-5D (0.53 ± 0.23 vs 0.58 ± 0.21, p = 0.008) than patients without such disorders. Postoperatively, in multivariable adjusted analyses, baseline SRD or SRA alone was associated with inferior improvement in the VAS neck pain score and a lower rate of achieving the MCID for VAS neck pain score at 3 and 12 months, but not at 24 months. At 24 months, patients with SRD or SRA alone experienced less change in EQ-5D scores and were less likely to meet the MCID for EQ-5D than patients without SRD or SRA. Furthermore, patient self-reporting of both psychological comorbidities did not impact PROs at all measured time points compared with self-reporting of only one psychological comorbidity alone. Each cohort (SRD or SRA alone, both SRD and SRA, and neither SRD nor SRA) experienced significant improvements in mean PROs at all measured time points compared with baseline (p < 0.05). CONCLUSIONS Approximately 12% of patients who underwent surgery for CSM presented with both SRD and SRA, and 29% presented with at least one symptom. The presence of either SRD or SRA was independently associated with inferior scores for 3- and 12-month neck pain following surgery, but this difference was not significant at 24 months. However, at long-term follow-up, patients with SRD or SRA experienced lower quality of life than patients without SRD or SRA. The comorbid presence of both depression and anxiety was not associated with worse patient outcomes than either diagnosis alone.

Spinal cord stimulation (SCS) has demonstrated effectiveness for neuropathic pain. Unfortunately, some patients report inadequate long-term pain relief. Patient selection is emphasized for this therapy; however, the prognostic capabilities and deployment strategies of existing selection techniques, including an SCS trial, have been questioned. After approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, a steering committee was formed to develop evidence-based guidelines for patient selection and the role of an SCS trial. Representatives of professional organizations with clinical expertize were invited to participate as committee members. A comprehensive literature review was carried out by the steering committee, and the results organized into narrative reports, which were circulated to all the committee members. Individual statements and recommendations within each of seven sections were formulated by the steering committee and circulated to members for voting. We used a modified Delphi method wherein drafts were circulated to each member in a blinded fashion for voting. Comments were incorporated in the subsequent revisions, which were recirculated for voting to achieve consensus. Seven sections with a total of 39 recommendations were approved with 100% consensus from all the members. Sections included definitions and terminology of SCS trial; benefits of SCS trial; screening for psychosocial characteristics; patient perceptions on SCS therapy and the use of trial; other patient predictors of SCS therapy; conduct of SCS trials; and evaluation of SCS trials including minimum criteria for success. Recommendations included that SCS trial should be performed before a definitive SCS implant except in anginal pain (grade B). All patients must be screened with an objective validated instrument for psychosocial factors, and this must include depression (grade B). Despite some limitations, a trial helps patient selection and provides patients with an opportunity to experience the therapy. These recommendations are expected to guide practicing physicians and other stakeholders and should not be mistaken as practice standards. Physicians should continue to make their best judgment based on individual patient considerations and preferences.

Background/importance Patient selection for spinal cord stimulation (SCS) therapy is crucial and is traditionally performed with clinical selection followed by a screening trial. The factors influencing patient selection and the importance of trialing have not been systematically evaluated. Objective We report a narrative review conducted to synthesize evidence regarding patient selection and the role of SCS trials. Evidence review Medline, EMBASE and Cochrane databases were searched for reports (any design) of SCS in adult patients, from their inception until March 30, 2022. Study selection and data extraction were carried out using DistillerSR. Data were organized into tables and narrative summaries, categorized by study design. Importance of patient variables and trialing was considered by looking at their influence on the long-term therapy success. Findings Among 7321 citations, 201 reports consisting of 60 systematic reviews, 36 randomized controlled trials (RCTs), 41 observational studies (OSs), 51 registry-based reports, and 13 case reports on complications during trialing were included. Based on RCTs and OSs, the median trial success rate was 72% and 82%, and therapy success was 65% and 61% at 12 months, respectively. Although several psychological and non-psychological determinants have been investigated, studies do not report a consistent approach to patient selection. Among psychological factors, untreated depression was associated with poor long-term outcomes, but the effect of others was inconsistent. Most RCTs except for chronic angina involved trialing and only one RCT compared patient selection with or without trial. The median (range) trial duration was 10 (0–30) and 7 (0–56) days among RCTs and OSs, respectively. Conclusions Due to lack of a consistent approach to identify responders for SCS therapy, trialing complements patient selection to exclude patients who do not find the therapy helpful and/or intolerant of the SCS system. However, more rigorous and large studies are necessary to better evaluate its role.

Abstract Background No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture–based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies PEP. We investigated the cause of breakthrough infection. Methods We reviewed medical records, laboratory results, and autopsy findings and performed whole-genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close patient contacts. Results Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, 3 (0.9%) warranted PEP. Conclusions This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture–based vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

Study Design. Retrospective cohort study. Objective. The present study is the first to assess the impact of paraspinal sarcopenia on patient-reported outcome measures (PROMs) following cervical laminoplasty. Background. While the impact of sarcopenia on PROMs following lumbar spine surgery is well-established, the impact of sarcopenia on PROMs following laminoplasty has not been investigated. Methods. We performed a retrospective review of patients undergoing laminoplasty from C4-6 at a single institution between 2010 and 2021. Two independent reviewers utilized axial cuts of T2-weighted magnetic resonance imaging sequences to assess fatty infiltration of the bilateral transversospinales muscle group at the C5-6 level and classify patients according to the Fuchs Modification of the Goutalier grading system. PROMs were then compared between subgroups. Results. We identified 114 patients for inclusion in this study, including 35 patients with mild sarcopenia, 49 patients with moderate sarcopenia, and 30 patients with severe sarcopenia. There were no differences in preoperative PROMs between subgroups. Mean postoperative neck disability index scores were lower in the mild and moderate sarcopenia subgroups (6.2 and 9.1, respectively) than in the severe sarcopenia subgroup (12.9, P=0.01). Patients with mild sarcopenia were nearly twice as likely to achieve minimal clinically important difference (88.6 vs. 53.5%; P<0.001) and six times as likely to achieve SCB (82.9 vs. 13.3%; P=0.006) compared with patients with severe sarcopenia. A higher percentage of patients with severe sarcopenia reported postoperative worsening of their neck disability index (13 patients, 43.3%; P=0.002) and Visual Analog Scale Arm scores (10 patients, 33.3%; P=0.03). Conclusion. Patients with severe paraspinal sarcopenia demonstrate less improvement in neck disability and pain postoperatively and are more likely to report worsening PROMs following laminoplasty. Level of Evidence. 3

Background: Residual fragments (RFs) after percutaneous nephrolithotomy (PCNL) have a significant impact on patients' quality of life and clinical course. There is a paucity of studies that evaluate the natural history of RFs after PCNL. The objective of this study is to compare rates of reintervention, complications, stone growth, and passage in patients with RFs >4, ≤4, and ≤2 mm after PCNL. Methods: Sites from the Endourologic Disease Group for Excellence (EDGE) research consortium examined data of PCNL patients from 2015 to 2019 with at least 1-year follow-up. RF passage, regrowth, reintervention, and complications were recorded and RFs were stratified into >4 and ≤4 mm groups, as well as >2 and ≤2 mm groups. Potential predictors for stone-related events after PCNL were determined using multivariable logistic regression analysis. It was hypothesized that larger RF thresholds would result in lower passage rates, faster regrowth, and greater clinically significant events (complications and reinterventions) than smaller RF thresholds. Results: A total of 439 patients with RFs >1 mm on CT postoperative day 1 were included in this study. For RFs >4 mm, rates of reintervention were found to be significantly higher and Kaplan–Meier curve analysis showed significantly higher rates of stone-related events. Passage and RF regrowth were not found to be significantly different compared with RFs ≤4 mm. However, RFs ≤2 mm had significantly higher rates of passage, and significantly lower rates of fragment regrowth (>1 mm), complications, and reintervention compared with RFs >2 mm. On multivariable analysis, older age, body mass index, and RF size were found to be predictive of stone-related events. Conclusions: With the largest cohort to date, this study by the EDGE research consortium further confirms that clinically insignificant residual fragment is problematic for patients after PCNL, particularly in older more obese patients with larger RFs. Our study underscores the importance of complete stone clearance post-PCNL and challenges the use of Clinically insignificant residual fragment (CIFR).

Significance Statement Nephron number currently can be estimated only from glomerular density on a kidney biopsy combined with cortical volume from kidney imaging. Because of measurement biases, refinement of this approach and validation across different patient populations have been needed. The prognostic importance of nephron number also has been unclear. The authors present an improved method of estimating nephron number that corrects for several biases, resulting in a 27% higher nephron number estimate for donor kidneys compared with a prior method. After accounting for comorbidities, the new nephron number estimate does not differ between kidney donors and kidney patients with tumor and shows consistent associations with clinical characteristics across these two populations. The findings also indicate that low nephron number predicts CKD independent of biopsy and clinical characteristics in both populations. Background Nephron number can be estimated from glomerular density and cortical volume. However, because of measurement biases, this approach needs refinement, comparison between disparate populations, and evaluation as a predictor of CKD outcomes. Methods We studied 3020 living kidney donors and 1354 patients who underwent radical nephrectomy for tumor. We determined cortex volume of the retained kidney from presurgical imaging and glomerular density by morphometric analysis of needle core biopsy of the donated kidney and wedge sections of the removed kidney. Glomerular density was corrected for missing glomerular tufts, absence of the kidney capsule, and then tissue shrinkage on the basis of analysis of 30 autopsy kidneys. We used logistic regression (in donors) and Cox proportional hazard models (in patients with tumor) to assess the risk of CKD outcomes associated with nephron number. Results Donors had 1.17 million nephrons per kidney; patients with tumor had 0.99 million nephrons per kidney. A lower nephron number was associated with older age, female sex, shorter height, hypertension, family history of ESKD, lower GFR, and proteinuria. After adjusting for these characteristics, nephron number did not differ between donors and patients with tumor. Low nephron number (defined by <5th or <10th percentile by age and sex in a healthy subset) in both populations predicted future risk of CKD outcomes independent of biopsy and clinical characteristics. Conclusions Compared with an older method for estimating nephron number, a new method that addresses several sources of bias results in nephron number estimates that are 27% higher in donors and 1% higher in patients with tumor and shows consistency between two populations. Low nephron number independently predicts CKD in both populations. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_06_22_JASN0000000000000124.mp3